搜索结果：Tobacco induced diseases

Tobacco (Nicotiana tabacum) leaf spot disease caused by fungal pathogens poses a major threat to crop yield and quality worldwide. Recently, Nigrospora coryli was identified as a novel causal agent of tobacco leaf spot in China, yet its biology, ecological interactions, and management strategies remained largely unexplored. In this study, we characterized N. coryli through growth physiology, phyllosphere microbiome analysis, microbial interaction assays, and fungicide sensitivity tests. The pathogen exhibited optimal growth on PDA at 28 °C and pH 6.0, with broad pH tolerance from 4 to 11 and a lethal temperature of 57 °C. Soluble starch and peptone were the preferred carbon and nitrogen sources, respectively. High-throughput sequencing revealed disease-associated phyllosphere shifts, including enrichment of Stenotrophomonas and reduced relative abundance of Pseudomonas in symptomatic leaves, as well as detection of Nigrospora and Sarocladium only in symptomatic samples. Functional screening identified multiple antagonistic microbes, with Aspergillus niger MGM reducing lesion size by 87.6% in planta, whereas co-inoculation with Pseudomonas syringae pv. angulata SLB-5-3 was associated with increased lesion size under controlled conditions. Among eight commercial fungicides, fludioxonil was the most potent (EC₅₀ = 0.0057 µg/mL), followed by the prochloraz-manganese chloride complex, difenoconazole, and fenaminstrobin. Synergistic interactions were observed in binary mixtures: fludioxonil + difenoconazole (1:4, SR = 1.7360), fludioxonil + fenaminstrobin (1:1, SR = 1.5365), and difenoconazole + fenaminstrobin (1:2, SR = 2.0219). These findings provide a basis for further evaluating candidate microbial antagonists and fungicide combinations for the management of N. coryli-induced tobacco leaf spot.

Acute myeloid leukemia (AML) is a major public health problem. However, the epidemiological pattern of the burden of AML attributable to tobacco globally remains unclear. This study aimed to characterize the global, regional, and national burden of AML attributable to tobacco from 1990 to 2021 and to forecast it to 2050. Data were sourced from the Global Burden of Disease (GBD) study 2021, and secondary dataset analysis was used in the present research. Age-standardized rates of tobacco-attributable AML deaths and disability-adjusted life years (DALYs) were analyzed, with estimated annual percentage change (EAPC) calculated. Age-period-cohort (APC) analysis was performed to quantify the age, period, and birth cohort effects on AML attributable to tobacco. A Bayesian APC model was subsequently us ed to project the disease burden of attributable to tobacco between 2022 and 2050. From 1990 to 2021, the burden of AML attributable to tobacco globally presented downward trends. The age-standardized death rate (ASDR) decreased from 0.214 [95% uncertainty interval (UI): 0.08-0.35] per 100000 people in 1990 to 0.176 (95% UI: 0.062-0.307) per 100000 people in 2021. The high sociodemographic index (SDI) regions had the highest ASDR and age-standardized DALYs rate for AML attributable to tobacco in 2021. The greatest burden of AML attributable to tobacco was the age group of 70-74 years among the risk factors of AML; tobacco shared at 11.5% of global deaths. As for the age effect, death due to AML attributable to tobacco increased with age, rising slowly before 40 years of age and accelerating sharply thereafter. The ASDR for males decreased from 0.3 per 100000 people in 2021 to 0.24 per 100000 people in 2022. Although the burden of AML attributable to tobacco had been on a downward trend from 1990 to 2021, it is particularly prominent in high SDI regions, high-income regions, and the elderly population.

Antipathogen defense; b-caryophyllene; vector-virus mutualism Plants respond to insect herbivory by producing and releasing distinctive blends of volatile compounds. These herbivore-induced plant volatiles (HIPVs) serve several roles, including direct defense through toxic or repellent effects on herbivores and indirect defense by attracting the herbivores' natural enemies (Bleeker et al. 2009; Veyrat et al. 2016). HIPVs also act as warning signals, informing undamaged tissues within the same plant and nearby plants of a pending insect attack (Heil and Bueno 2007). HIPVs are mostly composed of terpenes, fatty acid-derived compounds, and shikimic acid pathway metabolites. In response to certain HIPVs, neighboring plants enter a primed state, preparing for a future attack. As a result, when these primed plants are later attacked by the same herbivore, they can mount a faster and stronger defense response (Arimura et al. 2009). However, many specialized herbivores and pathogens can overcome, and often manipulate, these defenses to thrive on their specific host plants. Some insect vectors have evolved mutualisms with their viruses, e.g., some begomoviruses suppress terpenoid emissions that negatively affect their whitefly vectors (Bleeker et al. 2009). HIPV emissions vulnerable to manipulation include the generalist whitefly Bemisia tabaci-induced volatile blend (composed of the monoterpenes b-myrcene and q-cymene, and the sesquiterpene b-caryophyllene). These whitefly-induced volatiles prime salicylic acid-dependent defenses against pathogens in tomato plants while suppressing jasmonic acid-dependent defenses against herbivores, thus rendering neighboring tomato plants more susceptible to whiteflies (Zhang et al. 2019). This appears to be paradoxical and warrants further investigation. Although numerous species can attack plants simultaneously or sequentially, prior research has mostly focused on HIPV production in a single plant-herbivore or plant-pathogen interaction. Less is known about how plants respond to volatiles released by neighboring plants under simultaneous attack by multiple aggressors. Some studies suggest that plants may be able to distinguish volatile blends emitted by neighbors, attacked simultaneously by both viruses and their vectors, thereby priming appropriate defenses against each (Gong et al. 2023). A recent study by Zhang et al. (2026) examines the three-way interaction between tomato, the herbivorous whitefly B. tabaci, and the begomoviruses transmitted by this insect, namely, the tomato yellow leaf curl virus (TYLCV) and the papaya leaf curl China virus (PaLCuCNV). In this system, Zhang et al. (2026) investigated whether neighboring plants discriminate, through airborne cues, not only between herbivory but also between herbivory associated with virus risk. The group proved that the HIPV b-caryophyllene is induced earlier and more strongly after infestation by viruliferous whiteflies (insects harboring the virus) than after infestation by non-viruliferous whiteflies, whereas other volatiles in the same system, including methyl salicylate and b-myrcene, do not show the same distinctive early signature. The high b-caryophyllene level was a significant cue for neighboring plants to prime their defense mechanisms against the virus rather than the herbivore. The timing and context of b-caryophyllene release encode biologically specific information in this tri-trophic interaction, during vector-borne viral infection. Exposing neighboring plants to b-caryophyllene primes salicylic-acid-associated antiviral responses, including higher PR-1b and Ty-1 expressions, lowers virus accumulation under whitefly-mediated infection and enhances indirect defenses (Zhang et al. 2026). Zhang et al. (2026) used both synthetic b-caryophyllene and transgenic TPS12-overexpressing tomato lines to show that tomato lines constitutively emitting b-caryophyllene exhibit stronger resistance against viruses vectored by whiteflies. They further found that this is genotype-specific and only a subset of tomato genotypes exhibit significant viruliferous-whitefly-induced increases in b-caryophyllene emission and corresponding priming of PR-1b. This represents a conceptual shift from earlier interpretations of whitefly-induced volatile effects as those that largely favored the specialized insect herbivore (Zhang et al. 2019). In an earlier study from the same research group, volatile exposure was shown to suppress anti-whitefly defense while enhancing anti-pathogen defense in neighbors (Zhang et al. 2019), suggesting that plants were being manipulated to lower anti-herbivore defenses to the benefit of whiteflies. The present paper reinterprets that trade-off and shows that perhaps the plant is not being manipulated into making a mistake, but is instead making an adaptive allocation decision, prioritizing defense against the costlier threat of the virus. Rather than treating induced compounds simply as defense outputs, Zhang et al. (2026) show them as context-dependent signals, whose meaning depends on who is doing the attacking, what pathogen that attacker carries, and when the cue is released. The possibility that pathogens can also influence parasitoid foraging behavior was demonstrated by Martini et al. (2014), who reported for the first time that a parasitoid was "eavesdropping" on bacterial pathogen-mediated emission of methyl salicylate. Therefore, exploring the multitrophic relationships between plants, herbivores, pathogens, and parasitoids can help us understand the function of chemical signals in population regulation within an ecosystem. According to Zhang et al. (2026), the harm caused by begomoviruses, such as leaf stunting, yellowing, curling, and flower abortion, is more damaging and longer lasting than that caused by herbivores. This could be the reason why a plant would strategically favor antiviral defenses over anti-herbivore defenses when herbivores carry viruses. Plants may thus maximize their overall fitness under selection pressure from multiple invaders by using this trade-off mechanism to mitigate the effects of the more hazardous virus over herbivory. While there is evidence that b-caryophyllene has antimicrobial properties against certain bacterial species, which suggests possible direct viricidal effects, it remains unclear whether b-caryophyllene is directly viricidal or whether host physiology mediates its inhibitory effect on viral accumulation. Zhang et al. (2026) showed that, in the absence of a vector, exposure to b-caryophyllene alone does not activate antipathogen defenses. However, when viruliferous insects attack, antipathogen genes are upregulated, leading to reduced virus accumulation. No such upregulation of antipathogen genes was seen when b-caryophyllene was exposed to other host plants, such as tobacco and sweet pepper. b-caryophyllene thus does not act directly against viruses vectored by B. tabaci but rather enhances plant resistance to such pathogens through an indirect mechanism. The intricacy of plant defensive mechanisms in multiple-attacker situations was highlighted by the recent study of Zhang et al. (2026), which showed that b-caryophyllene is an airborne cue in the intricate interactions among plants, insect vectors, and related viruses. A fresh viewpoint on virus-vector mutualism is now available to investigate its potential use in the long-term control of insect-borne viruses. There is ongoing discussion on how HIPVs affect plant fitness when used for sustainable pest management. Hilgers et al. (2021) achieved the production of b-caryophyllene in the heterologous host Rhodobacter capsulatus and found that it significantly inhibited the growth of the destructive pathogen Sclerotinia sclerotiorum, causing white mold disease, and a devastating plant vascular wilt-causing fungus Fusarium oxysporum, indicating its applicability for the management of certain plant pathogenic fungi in agricultural crop production. Gao et al. (2024) demonstrated the increased stability of b-caryophyllene using nanoliposomes during a 14-day storage period, and its effective insecticidal activity against B. tabaci, which outperformed thiamethoxam, a widely used insecticide for whitefly management. Zhang et al. (2026) found that when plants are exposed to b-caryophyllene and infested with viruliferous whiteflies, their seed production increases, they attract parasitoids, and their virus load decreases. Importantly, a recent study cautions against the use of b-caryophyllene to develop kairomone-based insect lures, as it attracts the cacao mirid bug Helopeltis bakeri (Tavera et al. 2023). However, b-caryophyllene is a highly pleiotropic ecological signal; as a terpene negatively impacting pests such as Spodoptera litura (Mahajan et al. 2022) and Myzus persicae (Chohan et al. 2023); as an alternative to methyl eugenol for the concurrent use of the male annihilation technique and sterile insect technique in fruit fly (Bactrocera zonata) management (ul Haq et al. 2024); as a lure for parasitoids (Zhang et al. 2020) and as a gender-specific terpene produced by predators (Brown et al. 2006). b-caryophyllene has already been implicated in direct and indirect defense, in herbivore attraction or repellence depending on context, and in broader volatile signaling networks. Because of these multiple effects, one must be careful not to overstate the specificity of b-caryophyllene. Secondly, whether neighboring plants perceive b-caryophyllene itself as a uniquely informative cue of virus risk, rather than a proxy embedded in a broader blend or exposure history, remains an open mechanistic question. After careful consideration of the organisms involved, b-caryophyllene may be incorporated to manage vector-borne viral diseases, for example, by using cultivars that show strong antipathogen defenses upon exposure to this sesquiterpene.

Understanding retailer advertising has been identified as critical for developing effective policies to reduce tobacco product use, as these forms of advertising are among the tobacco industry's largest expenditures. Online retailer marketing has grown rapidly, and in this study, we sought to describe the marketing practices of these retailers. Between March and July 2022, we conducted keyword searches (e.g. 'buy e-cigs', 'buy vapes') with the Brave search engine, embedded in the Brave browser, to identify online tobacco retailers, using the inclusion criteria: English-language websites of online retailers selling e-cigarette products that allowed online ordering and the sale of products to customers in the United States. Measures included name, address, and landing page characteristics, including products, brands, product types, seasonal specials, social media links, age gating, and whether the retailer sold non-tobacco products. Results are reported descriptively. We identified 97 unique online tobacco retailers. Of these, 58 (60%) had set a restriction on browsing based on age. E-cigarettes, both disposable and reusable, were the most available products, followed by liquid nicotine ('vape juice'). Thirty-seven percent of online tobacco retailers sold cannabis products, and 38% of retailer websites listed other types of products for sale (e.g. bongs, dab rigs, cannabis apparel, psilocybin chocolates). Our findings indicated that online tobacco retailers heavily marketed flavored products, and a majority sold derived cannabis products. Future research should continue to investigate whether this marketing conflicts with stated federal regulatory goals, and whether the U.S. Food and Drug Administration should expand enforcement of existing regulations on tobacco and derived cannabis products.

Plant virus-based vectors are gaining significant attention as bioreactors for recombinant protein production due to their broad host range, robust expression levels and cost-effectiveness; however, their practical utility is frequently constrained by severe viral pathogenicity. Notably, the utility of potato virus Y (PVY), the type member of the genus Potyvirus, is severely hampered by its elicitation of tobacco vein necrosis (TVN). Here, we demonstrate that a single synonymous substitution (AAA to AAG) at the K178 codon of P1 causes almost no TVN. Mechanistically, the P1-AAG mutation attenuates the synergistic RNA silencing suppression (RSS) activity typically mediated by the P1/HC-Pro complex. This functional impairment abrogates the virus-induced upregulation of specific host microRNAs (miR6020, miR6164 and miR6021). Using this non-necrotic PVY-P1-AAG vector, we engineered an optimised bioproduction platform. By integrating a GFP-HRV3C fusion tag system with affinity purification and subsequent proteolytic cleavage, we achieved the high-yield synthesis of recombinant human interferons (IFN-α1b and IFN-α2b) in Nicotiana benthamiana and Nicotiana tabacum 'Xanthi'. Codon optimisation of the cargo genes further enhanced protein accumulation, achieving yields of up to 55.2 μg/g fresh leaf weight. Taken together, these results provide new insights into how synonymous substitutions influence potyviral pathogenicity and validate the symptomless P1-AAG vector as a robust system for biomanufacturing value-added proteins.

We aimed to estimate the prevalence of cigarette smoking, e-cigarette, and heated tobacco product use behaviors and their associated factors among adult Malaysians. A cross-sectional online survey was conducted in December 2024 among a nationally representative sample of 1000 adult Malaysians (≥18 years). We used a questionnaire adapted from the Global Adult Tobacco Survey. Binary logistic regression analyses were performed to identify factors associated with tobacco and nicotine product use. The overall prevalence of current smoking was 28.6% (95% CI: 25.8-31.4), with a mean age of smoking initiation of 21.5 years. Awareness of e-cigarettes was high (92.4%), with 14.6% (95% CI: 12.5-17.0) and 13.4% (95% CI: 11.4-15.8) reporting current daily and non-daily use, respectively. Fewer respondents were aware of heated tobacco products (HTPs, 548.5%), with 4.5% (95% CI: 3.4-6.1) and 10.0% (95% CI: 8.2-12.1) reporting current daily and non-daily use, respectively. Current smoking (AOR=44.19; 95% CI: 24.78-78.81 for e-cigarettes; AOR=31.0; 95% CI: 13.58-73.57 for HTPs), male sex, younger age, and exposure to advertisements were significantly associated with e-cigarette and HTP use. A smoke-free home environment was a protective factor against e-cigarette (AOR=0.44; 95% CI: 0.24-0.80) and HTP use (AOR=0.27; 95% CI: 0.13-0.55). Continued surveillance of nicotine product use is essential. Tobacco control measures under the new Public Health Act should include specific regulations for e-cigarettes and heated tobacco products, particularly targeting younger populations.

Tobacco use prevention among university students requires evidence on which educational program features students prefer. This study used a discrete choice experiment (DCE) embedded in a randomized controlled trial (RCT) to quantify Chinese never-tobacco-using university students' preferences for attributes of a tobacco control health education program. A DCE with six two-level attributes (organizer, content format, organization mode, frequency, educational content, delivery location) was administered to 260 never-tobacco-using university students enrolled in a Protection Motivation Theory (PMT)-based RCT. Seven choice sets, each containing two unlabeled alternatives, were presented via an online survey platform. Conditional logit models with cluster-robust standard errors estimated attribute preferences; Wald interaction tests assessed preference heterogeneity by trial arm, sex, parental smoking, and peer smoking. Of the 260 respondents, 192 (73.8%) were female, and 243 (93.5%) were undergraduates. Students significantly preferred video-based content (β= -0.1899; 95% CI: -0.2723 - -0.1074), online delivery (β= -0.1698; 95% CI: -0.2525 - -0.0872), and comprehensive cigarette-plus-e-cigarette content (β= -0.1320, 95% CI: -0.2147 - -0.0493). Content format (32.0%), delivery location (28.6%), and educational content (22.2%) together accounted for 82.8% of relative attribute importance. DCE preferences did not differ between trial arms (all Wald interaction p>0.33). A significant sex × delivery location interaction was observed (p=0.019). Chinese never-tobacco-using university students prefer video-based, online, comprehensive tobacco and e-cigarette education. These demand-side preferences may inform the design of future campus-based prevention programs. The absence of trial arm differences supports the validity of the embedded DCE-RCT design. The study is registered on the official website of Chinese Clinical Trial Registry. ChiCTR2300068240.

Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung disorder driven not only by tobacco smoke (TS) but also by environmental toxicants, including particulate matter (PM) and heavy metals such as lead (Pb) and cadmium (Cd). Although oxidative stress and inflammatory cell death are central to COPD pathogenesis, effective disease-modifying therapeutic targets remain limited. Here, we identify that nerve injury-induced protein 1 (Ninjurin1, Ninj1), a damage-responsive cell adhesion molecule implicated in inflammatory cell death, as a previously unrecognized mediator of toxicant-induced COPD-like pathology. We designed and screened a panel of 22 2'-O-methoxyethyl (2'-MOE) gapmer antisense oligonucleotides (ASOs) targeting Ninj1. Cell type-specific knockdown efficiency was assessed by flow cytometry and real-time PCR. The therapeutic efficacy of lead candidates was evaluated by histopathological analysis, immunofluorescence, and molecular readouts of inflammation and tissue injury in a murine COPD model induced by long-term inhalation of a mixture of Pb and Cd (Pb/Cd). ASO safety was further assessed both in vitro and in vivo, including acute and chronic toxicity studies. Ninj1 expression was markedly upregulated in the lungs of mice following exposure to TS components (NNK and BaP), particulate matter (PM), or Pb/Cd. Intratracheal delivery of Ninj1-targeting ASO attenuated hallmark COPD-associated features, including alveolar airspace enlargement, mucus hypersecretion, oxidative stress, matrix metalloproteinase activity, and fibrotic lesions, without evidence of overt systemic toxicity. These findings establish Ninj1 as a critical mediator of chronic lung inflammation and a translationally relevant therapeutic target, highlighting Ninj1-directed ASO therapy as a promising strategy for the treatment of environmental toxicant-induced respiratory diseases.

Heated tobacco products are often marketed and perceived as less harmful than regular cigarettes, although their acute cardiovascular toxicity is unknown. In this study, the acute effect of exclusive IQOS use on several cardiovascular parameters was assessed, and compared with those of both exclusive cigarette smokers and never smokers of tobacco products. The puffing behavior of both groups of tobacco users was also characterized. An independent quasi-experimental study was conducted in Milan, Italy, in March-June 2024. Three groups of participants - frequency matched by age and gender - were recruited: exclusive conventional cigarette smokers (n=25, CS), exclusive IQOS users (n=26, IU), and never smokers (n=27, NS). All participants were aged &#x2265;18 years, had a body mass index between 18.5 and 25 kg/m2, did not have respiratory or cardiovascular diseases, nor were they taking medications associated with these. The acute cardiovascular impact associated with the use of a regular cigarette or IQOS was measured by comparing systolic and diastolic blood pressure, and heart rate prior to (T0) and upon (T1) product consumption. Video-assisted measurement of the total length of the smoking session, number of puffs, puff duration, and inter-puff interval was carried out. The mean heart beats per minute of conventional cigarette (87.4 at T1 vs 74.6 at T0) and IQOS users (86.7 at T1 vs 75.5 at T0) upon product use were higher compared with their baseline measurement (p<0.001) and with the control group (70.5 at T1 vs 74.1 at T0; p<0.001). The increases (T1-T0) in the three cardiovascular measures observed for IQOS users were not different with those of conventional cigarette smokers and significantly higher than the changes of never smokers (&#x394; systolic blood pressure: -5.9 in NS, 2.4 in CS and 0.3 in IU; &#x394; diastolic blood pressure: -1.3 for NS, 4.6 for CS and 3.1 for IU; &#x394; heart rate: -3.7 for NS, 12.8 for CS and 11.1 for IU). IQOS users exhibited shorter smoking sessions than cigarette smokers (4 vs 3.5 minutes, p<0.05), in which they took more frequent (16.2 s for CS, 11.8 s for IU, p<0.001) and longer puffs (1.7 s for CS, 2.3 s for IU, p<0.001). This study shows analogous acute physiological changes of conventional and heated tobacco products on the human heart. The reported differences in puffing behaviors between cigarette and IQOS users show, to our knowledge, for the first time, the importance of using real-life puffing behavior data in laboratory settings.

Chronic obstructive pulmonary disease (COPD) is a common progressive respiratory disease with persistent airflow limitation, chronic airway inflammation, and limited early diagnostic biomarkers and targeted therapies. MicroRNAs (miRNAs) are involved in COPD pathogenesis, but the role of microRNA-129-5p (miR-129-5p) in COPD is unclear. This study investigated miR-129-5p's association with COPD susceptibility, its regulation on cigarette smoke extract (CSE)-induced bronchial epithelial cell injury, and the mechanism involving intercellular cell adhesion molecule 1 (ICAM1) and RELA. The study included a cross-sectional study and in vitro experiments. The cross-sectional study (Hanyang Hospital, March 2022-May 2024) collected serum from 126 COPD patients and 120 controls to detect miR-129-5p, ICAM1, and RELA via quantitative real-time polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) curve area (AUC), multivariate logistic regression, and Pearson correlation were used for analysis. In vitro, human bronchial epithelial cells (BEAS-2B) were divided into 6 groups for the CSE-induced injury model; Cell Counting Kit-8 (CCK-8), flow cytometry, enzyme-linked immunosorbent assay (ELISA), and dual-luciferase assay detected cell functions and miR-129-5p-ICAM1 targeting. Serum miR-129-5p was significantly downregulated in COPD patients, with elevated ICAM1, RELA, and inflammatory factors. It distinguished COPD from controls (AUC=0.88; 95% CI: 0.84-0.92, p<0.001) and was an independent susceptibility factor (adjusted odds ratio, AOR=0.15; 95% CI: 0.08-0.26, p<0.001). miR-129-5p was negatively associated with inflammatory factors and positively associated with pulmonary function. CSE inhibited miR-129-5p and induced injury; its overexpression reversed injury, knockdown exacerbated it, and it targeted ICAM1, whose overexpression abrogated miR-129-5p's protection. Serum miR-129-5p was downregulated in COPD patients, while cellular evidence indicated that it potentially alleviates CSE-induced injury by targeting ICAM1 and downregulating RELA, providing preliminary evidence for COPD pathogenesis; further large-scale studies are needed to verify its clinical value.

The present study aimed to investigate macrophage polarization imbalance and its association with sustained NF-&#x3ba;B/NLRP3 signaling under chronic inflammatory stimulation using both in vivo and in vitro COPD-related models. This experimental preclinical study was conducted between March and September 2023, at Shanghai Tenth People's Hospital. A chronic obstructive pulmonary disease (COPD)-like inflammatory model was established in C57BL/6J mice (n=5 per group) through combined chronic cigarette smoke (CS) exposure (4 hours/day, 5 days/week for 15 weeks) and intranasal lipopolysaccharide (LPS) administration (7.5 &#x3bc;g on days 1 and 14), together with an in vitro cigarette smoke extract (CSE)-induced RAW264.7 macrophage model (10% CSE for 24 hours). Macrophage M1/M2 polarization and inflammatory responses were assessed using ELISA, qRT-PCR, immunohistochemistry, Western blotting, and flow cytometry. Airflow limitation was observed in CS-exposed model mice, with significant reductions in FEV0.05/FVC (21.70 &#xb1; 0.96 vs 27.50 &#xb1; 0.94%, p<0.0001) and FEV0.1/FVC (77.39 &#xb1; 2.62 vs 87.21 &#xb1; 1.95%, p<0.001), along with increased lung resistance (RL: 1.22 &#xb1; 0.13 vs 0.97 &#xb1; 0.02 cmH2O/(mL/s), p<0.01). Histological examination revealed thickened bronchial walls, disrupted alveolar structure, and inflammatory cell infiltration. TNF-&#x3b1; (BALF: 290.6 &#xb1; 7.58 vs 125.6 &#xb1; 5.30 pg/mL, p<0.0001), IL-6 (BALF: 67.92 &#xb1; 3.02 vs 44.42 &#xb1; 2.62 pg/mL, p<0.001), and IL-1&#x3b2; (BALF: 120.3 &#xb1; 8.24 vs 87.52 &#xb1; 3.40 pg/mL, p<0.01) levels increased dramatically in both CS-exposed mice and CSE-induced RAW264.7 cells, whereas IL-10 levels decreased (BALF: 46.12 &#xb1; 1.71 vs 77.19 &#xb1; 3.96 pg/mL, p<0.001). CS and CSE exposure induced M1 macrophage polarization in mice, as well as 10% CSE-induced RAW 264.7 cells, which may be related to the activation of the NF-&#x3ba;B/NLRP3 signaling pathway.

While cumulative smoking exposure is a well-established risk factor of chronic respiratory disease (CRD), a behavioral indicator of nicotine dependence, the time to first cigarette after waking (TTFC) may provide additional prognostic information. However, prospective evidence linking TTFC to incident CRD, particularly in Chinese populations, remains limited. This study aims to investigate the association between TTFC and incident CRD risk in middle-aged and older men. This prospective cohort study included 5198 Chinese men aged &#x2265;45 years without baseline CRD who were enrolled in the China Health and Retirement Longitudinal Study (CHARLS). TTFC was categorized as >60, 31-60, 6-30, and <6 minutes after waking, with never smokers as the reference group. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CRD. Laplace regression was applied to evaluate differences in median disease onset time. Joint effects of TTFC and smoking pack-years were also assessed. During 44105 person-years of follow-up, 856 incident CRD cases occurred (incidence rate: 19.41 per 1000 person-years). Earlier, TTFC was associated with progressively higher CRD risk in a dose-response manner (p for trend=0.025). Compared with never smokers, participants with TTFC <6 minutes had a significantly higher CRD risk (HR=1.31; 95% CI: 1.02-1.66). Laplace regression showed that TTFC <6 minutes was associated with 0.75 years earlier median disease onset (95% CI: -1.45 - -0.06). Joint exposure analysis indicated that participants with both early TTFC and heavy smoking exposure had the highest risk (HR=1.30; 95% CI: 1.10-1.51), with evidence of additive interaction (attributable proportion, AP=0.177; 95% CI: 0.005-0.349). Earlier TTFC is independently associated with increased risk and earlier onset of CRD among Chinese middle-aged and older men. TTFC may serve as a simple and potentially informative behavioral marker for identifying smokers with a higher risk of CRD.

[This corrects the article DOI: 10.18332/tid/218296.].

What is the incidence of premature ovarian insufficiency (POI) and its associated factors in Ontario, Canada, between 1995 and 2019? The incidence of POI increased after 2011, driven primarily by non-iatrogenic POI, and was highest among women with a history of endometriosis. Recent estimates suggest a global POI prevalence of &#x223c;3.7%, with increasing rates over time. POI has heterogeneous etiologies, including genetic, autoimmune, infectious, and iatrogenic causes; however, the cause remains unknown in &#x223c;70% of non-iatrogenic cases. Existing incidence estimates are limited by recall bias, cross-sectional designs, small sample sizes, and limited assessment of associated factors. This population-based cohort study included all women aged &#x2264; 39&#x2009;years residing in Ontario between 1995 and 2019. Follow-up continued until POI diagnosis, age 40&#x2009;years, death, loss of provincial health insurance, or end of the study period. POI was defined using administrative health data as a diagnosis occurring before age 40&#xa0;years identified by either (i) surgical menopause or (ii) &#x2265;1 physician consultation coded as menopause (ICD-9 627). Annual incidence rates (IRs) were calculated using census data, with the Ontario female population aged &#x2264; 39&#x2009;years as the denominator. POI was classified as non-iatrogenic, surgical, post-chemotherapy and/or radiotherapy, or combined surgical with chemotherapy and/or radiotherapy. Associations between clinical factors and POI were estimated using age-adjusted modified Poisson regression to derive incidence rate ratios (IRRs). Among 3&#xa0;635&#xa0;702 eligible women, 168&#xa0;173 developed POI from any etiology (IR 389.4 per 100&#xa0;000 person-years). Median follow-up was 11&#x2009;years (IQR 6-18), and median age at POI diagnosis was 31&#x2009;years (IQR 25-36). IRs were 351.4 per 100&#xa0;000 person-years for non-iatrogenic POI, 30.2 for surgical POI, 5.5 for post-chemotherapy and/or radiotherapy POI, and 2.3 for combined surgical with chemotherapy and/or radiotherapy POI. Overall POI incidence declined between 2002 and 2008, followed by a sustained increase through 2019, largely attributable to non-iatrogenic POI. The incidence of surgically induced POI decreased from 60 per 100&#xa0;000 person-years in 1995 to 20 in 2019, while combined surgical with chemotherapy and/or radiotherapy POI increased steadily over the study period. Factors associated with higher POI incidence included endometriosis (IRR 3.45, 95% CI 3.39, 3.52), cancer treated with chemotherapy or radiotherapy (IRR 2.01, 95% CI 1.89, 2.14), drug or tobacco use (IRR 1.59, 95% CI 1.51, 1.67), chromosomal disorders (IRR 1.50, 95% CI 1.42, 1.59), and autoimmune diseases (IRR 1.19, 95% CI 1.17, 1.22). Use of administrative health data may result in outcome misclassification and limited availability of detailed clinical and demographic information. These findings provide contemporary population-based estimates of POI incidence and identify endometriosis as a major associated factor. The marked decline in surgically induced POI over time suggests increased adoption of ovarian-preserving surgical approaches, while rising non-iatrogenic POI incidence underscores the need for improved risk stratification, counselling, and further studies to elucidate underlying mechanisms and modifiable risk factors. Canadian Menopause Society. Nothing to disclose. N/A.

Conventional tobacco use causes a wealth of diseases and adversely affects cells and organ systems across the body. The long-term effects of e-cigarette vaping on the same remain unclear. Identifying early pathogenic signals at the organ level via animal models may shed light on potential downstream effects in humans. Here we investigate transcriptomic changes in the kidney and liver, organs known to be damaged by long-term combustible tobacco use, of mice exposed daily to e-cigarette aerosols (vapor) with or without nicotine. C57BL/6 male 6-8 week-old mice underwent whole-body exposure to room air, e-cigarette (3rd generation box mod) vapor containing 70:30 propylene glycol and glycerin (PG: Gly) without nicotine (Vehicle), and e-cigarette vapor with 6&#xa0;mg/mL freebase nicotine in 70:30 PG: Gly (E-cig) for 1&#xa0;h daily for 3 months. RNA sequencing on kidney and liver tissues and apriori gene set analysis were performed. Unbiased principal component analysis identified closer clustering of E-cig and Vehicle groups, relative to Air, in the kidney. Assessment of the a priori gene set found nicotine to be associated with greater transcriptomic changes in the kidney while vehicle chemicals induced greater changes in the liver. Alterations in expression of Car3 and Foxo3 identify oxidative stress and inflammation in the renal system associated with e-cigarette exposure, while dysregulated Il6ra and Lpin1 in the liver highlight disruptions in lipid metabolism and immune signaling. Chronic inhalation of e-cigarette vapor alters gene expression in downstream organs, in a pattern most consistent with promotion of fibrosis and metabolic dysregulation, underscoring the need to define long-term pathophysiologic effects of e-cigarette vaping across the body.

While public smoking bans help reduce smoking behavior, tobacco control in China is mainly managed locally. The effects of regional regulations on individual smoking are unclear. This study analyses public smoking bans across several cities to inform local and national tobacco control efforts. This study is a secondary data analysis using the 2010-2020 China Family Panel Studies (CFPS) nationwide dataset. The study adopts an observational design covering a 10-year period from 2010 to 2020, with data collected biennially across waves. The study population comprised respondents, aged &#x2265;16 years from the CFPS 2010-2020 waves, who resided in the 37 cities selected for this quasi-experimental design. Individuals were included if they had complete data on smoking behavior, demographic characteristics, and key socioeconomic variables. Local tobacco control regulations did not significantly affect smoking status. They were related to the amount smoked (&#x3b2;=0.374; 95% CI: 0.115-0.633; p=0.005), with a significant positive correlation and heterogeneity observed in the subgroup analysis. In Hangzhou, the smoking probability increased by 0.021 (95% CI: 0.013-0.030, p<0.001) after policy enactment, and daily cigarette consumption among smokers increased by 0.696 (95% CI: 0.507-0.886, p<0.001). In Tianjin, the smoking probability decreased by 0.040 (95% CI: -0.048 - -0.032, p<0.001), and daily cigarette consumption dropped by 1.532 (95% CI: -1.684 - -1.379, p<0.001). In Guangzhou, the policy had no effect on smoking probability but reduced daily cigarette consumption by 0.316 (95% CI: -0.507 - -0.124, p=0.002). The effects of tobacco control policies vary significantly across different cities. This study identifies substantial regional heterogeneity in the effects of local public-place smoking bans, supporting the need for national standardization and context-specific regulatory strategies.

Depression is a globally prevalent affective disorder closely associated with environmental factors and neurological dysfunction, affecting over 300 million people worldwide and imposing a heavy burden on families and healthcare systems. As the core addictive bioactive component in tobacco, nicotine is intimately linked to an increased risk of depression, but its underlying molecular mechanisms remain unclear. This study aimed to explore the molecular mechanisms of nicotine-induced depression and identify the core molecular targets and pathways involved. This study integrated network toxicology, molecular docking, and Mendelian randomization (MR). Nicotine's structure and SMILES were retrieved from PubChem for toxicity analysis via ADMETlab 3.0 and Protox3.0. Potential targets of nicotine and depression-related genes were screened from databases including GeneCards, OMIM, and ChEMBL. Common targets were obtained via Venny for PPI network construction, core target screening, GO/KEGG enrichment analysis, and molecular docking of the top 5 targets. MR verified causal associations with depression. Nicotine exhibited significant neurotoxicity (probability=0.951), respiratory, hepatotoxic, and nephrotoxic effects. A total of 69 common targets were identified, including DRD2, CHRNA4, and STAT3. GO enrichment involved biological processes like excitatory postsynaptic potential and KEGG pathways such as cAMP signaling. Molecular docking showed favorable binding affinity (binding energies < -5.0 kcal/mol). MR confirmed that higher CHRNA4 expression in the Nucleus Accumbens increased depression risk (IVW, OR=1.02; 95% CI: 1.01-1.04, p=0.003). This study demonstrated that nicotine exacerbates depressive-like behaviors by binding to core targets, including DRD2 and CHRNA4, and regulating dopaminergic and cholinergic pathways. These findings provide mechanistic insights for elucidating the underlying molecular mechanisms of nicotine-induced depression, while the identified targets and pathways offer potential directions for subsequent mechanistic validation and targeted studies of depression associated with nicotine exposure.

The toxic effects of air pollutants on the airway epithelium are associated with oxidative stress, a pro-inflammatory response, and impaired innate immune responses. The chronic exposure to noxious factors leads to cumulative damage to the alveolar compartment, reduced diffusion capacity, and impaired lung function. This study aimed to investigate the biological responses of bronchial epithelial cells exposed to PM2.5 and microplastic, following prior induction of acute, chronic, and allergic epithelial injury. Primary, normal bronchial epithelial cells were cultivated in air-liquid interface (ALI) in models of normal, acute (lipopolysaccharide (LPS) treated), chronic (cigarette smoke extract (CSE) treated for 14 days), and allergic (house dust mite (HDM)&#xa0;+&#xa0;IL-13 treated for 3 days). Simultaneously, cells were divided into two groups: uninjured or physically injured by a scratch. Cells were then stimulated with microplastic fibres (200&#xa0;&#x3bc;g/cm2) and PM2.5 (50&#xa0;&#x3bc;g per insert) applied to the top of the epithelial cell layer for 48&#xa0;h. Combined exposure to PM2.5 and microplastics induced profound cytotoxic effects across all models. Mechanical injury modulated inflammatory responses in a model-dependent manner, with the most pronounced dysregulation observed in allergically primed epithelial cells. In control and LPS-stimulated cultures, co-exposure to PM2.5 and microplastics significantly disrupted epithelial barrier integrity. PM2.5 and microplastic exposure were associated with increased TGF-&#x3b2; and EGFR expression across several injury models, with a tendency toward enhanced TGF-&#x3b2; signalling in secretory epithelial cells under chronic and allergic conditions, largely independent of mechanical injury. Overall, pollutant-induced responses varied according to the underlying epithelial injury state. Atmospheric pollutants influenced epithelial immune response, contributing to airway epithelial injury and affecting regenerative capacity, particularly when cellular biology was additionally compromised by bacterial, tobacco or allergic stimuli.

Tomato yellow leaf curl virus (TYLCV) poses a serious threat to global tomato production. Current management strategies remain limited, highlighting the need for novel antiviral agents. In this study, we evaluated the efficacy of a newly synthesized pyrimidine-guanidine derivative, YYH-6, against TYLCV in tomato (Solanum lycopersicum cv. Micro-Tom) and investigated its underlying mechanisms. Foliar application of YYH-6 significantly reduced viral accumulation and alleviated disease symptoms. Transcriptomic analysis revealed that YYH-6 treatment upregulates defense-related pathways such as plant-pathogen interaction, MAPK signaling, and phenylpropanoid biosynthesis. Results of TRV-based virus-induced gene silencing (VIGS) further indicate that RPP13 and ALS2 function as important resistance genes induced by YYH-6. Activity-based protein profiling, LC-MS/MS, and reverse genetic verification by VIGS indicate that serine hydroxymethyltransferase and STI1 domain-containing proteins are potential target proteins of YYH-6 for TYLCV inhibition. Our findings demonstrate that YYH-6 suppresses TYLCV infection through multitarget modulation of host defense pathways, making it a promising candidate for sustainable management of tomato viral diseases.