Trained immunity is a state of heightened immune response that is initiated in hematopoietic stem cells (HSCs) and mediated mainly by their myeloid progeny. Aging-associated inflammation drives many aging-related diseases, yet its biological origin is largely unknown. Here we show that SIRT3, a mitochondrial deacetylase highly expressed in HSCs but reduced during aging, suppresses the HSC response to aging that drives maladaptive trained immunity, chronic inflammation and tissue functional decline in mice. Overexpression of SIRT3 in HSCs not only ameliorates aging-associated HSC decline, but also improves the function of distant tissues, including attenuation of age-related declines in cognition and motility, via myeloid cells with modulated inflammatory programs. These findings reveal that HSC aging is a driver of aging-associated inflammation through maladaptive trained immunity and broaden the possible clinical applications of targeting HSCs from hematological diseases to include countering aging-associated physiological decline and improving healthspan.
Male infertility is complex, driven by impaired endocrine signalling, germ-somatic cell communication, and epigenetic regulation of spermatogenesis. LH/cAMP/PKA signalling in Leydig cells and FSH-mediated regulation in Sertoli cells have been extensively studied. The combined effects of these pathways on testicular physiology and clinical infertility are unknown. This review integrates hypothalamic-pituitary-gonadal axis signalling, intra-testicular epigenetic oversight, and environmental variables at the systems level. Integrating LH and FSH-dependent signalling with somatic cell activity, epigenetic programming during spermatogenesis, and endocrine disruptor effects on these networks. Despite recent improvements in single-cell and spatial transcriptomics, testicular heterogeneity and its integration processes remain unexplained. This review identifies key barriers that hinder molecular discoveries from becoming clinical diagnoses and therapies. This paradigm links biological pathways to infertility symptoms. It provides new possibilities for biomarker development and targeted therapeutics by including endocrine, epigenetic, and environmental factors on testicular function, prompting future research into translational routes that connect molecular endocrinology and clinical care for infertility.
The glymphatic system is a brain-wide clearance pathway that maintains central nervous system homeostasis by facilitating cerebrospinal fluid (CSF)-interstitial fluid (ISF) exchange and metabolic waste removal. Accumulating evidence links glymphatic dysfunction to neurodegeneration, cerebrovascular disease, and sleep-related disorders, motivating the search for clinically deployable imaging biomarkers. Imaging has become central to this effort, spanning tracer-based approaches and non-invasive MRI methods such as phase-contrast magnetic resonance imaging (MRI), functional MRI-derived CSF dynamics, structural MRI markers including MRI-visible perivascular spaces and parenchymal CSF (pCSF) mapping, and diffusion-based indices including diffusion tensor image analysis along the perivascular space (DTI-ALPS). This review aims toprovide a translation-oriented perspective that reframes the current literature by disentangling what each modality actually measures-such as tracer transport, fluid compartment morphology and distribution, pulsatility-related motion, diffusion-sensitive exchange constraints, or vascular-interface perfusion/exchange physiology-from what it is often interpreted to represent (glymphatic clearance), and by proposing a practical roadmap to improve physiological specificity and clinical utility. Importantly, no truly non-invasive MRI technique can currently directly measure glymphatic transport or CSF-ISF exchange in humans, so existing readouts should be treated as surrogate markers with known confounds. We highlight emerging methods sensitive to slow flow and exchange and outline priorities for clinical translation, including harmonized protocols, cross-site reproducibility, mechanistic validation, and outcome-linked validation in prospective studies.
Investigators must frequently apportion precious sample volumes between multiple assays to measure the viability, potency, and compositional phenotype of cell therapy products and clinical research samples. However, the use of disparate assay modalities may miss critical information which links the expression profile of cells with functional activity, especially when these activated cell populations are rare. To address this shortcoming, we describe in this short report the creation of a 38-color spectral flow cytometry panel for the phenotypic and functional characterization of antigen reactive T cell populations within cellular therapy products and clinical research samples. Our investigations identified that up to 29 potentially co-expressing markers were able to be identified on mixed sample populations using this panel, including phenotype, activation, and exhaustion markers, as well as intracellular cytokine production. Our calculations also highlight spectral flow cytometry is a more efficient use of technician time, reagent cost, and product sample usage as compared with an equivalent set of traditional flow cytometry panels.
This study aims to explore Sporosarcina globispora MTCC 4776 to produce levan using submerged fermentation. The assessment of carbon and nitrogen sources revealed that a moderate concentration of sucrose and tryptone improved levan production. Eight of the independent variables, concentration of sucrose, tryptone, CaCl₂·2H₂O, K₂HPO₄, MgSO₄·7H₂O, % of inoculum, incubation time and agitation speed was assessed with twelve experimental runs through Plackett-Burman design. Concentration of sucrose, tryptone and agitation speed were found to be significant. These factors were further optimized using Central Composite Design, yielding a maximum of 1.41 g/L of levan, which is a 6.2-fold increase compared to unoptimized conditions. The extracted levan was characterized for its structure and physicochemical properties by FTIR, 1H/13C-NMR, TGA/DTG, DSC, and XRD. These results confirmed the presence of a β-(2 → 6)- linked fructofuranosyl chain with excellent thermal stability and a semi-crystalline structure. In the future, studies on the purification and application of levan will be conducted to assess the sample's potential.
The urban environment increases the risk of inflammatory bowel disease (IBD). Specific environmental exposures involved in IBD etiology remain unknown. We examined the association between outdoor artificial light at night (ALAN) and IBD incidence, surgery, and health services utilization (HSU). Using population-based deterministically linked health administrative data from Ontario, Canada we conducted a birth cohort study (incidence), matched case-control study (incidence), and cohort study (surgery, HSU). Individuals with IBD were identified using previously validated algorithms. ALAN, the average digital number of lights consistently present, was a 3-level variable: <35 (reference), 35-60, > 60. We used Cox proportional hazards models (birth cohort, surgery), conditional logistic regression (matched case-control study), and Poisson regression (HSU). Among 3 929 374 individuals in the birth cohort, 5539 (0.1%) developed IBD; no association between ALAN at birth and IBD was observed (35-60: hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.87-1.22; >60: HR 0.93, 95% CI 0.78-1.11). Among 32 176 IBD cases matched to 160 709 controls, high ALAN was associated with a lower IBD risk (>60: odds ratio [OR] 0.84, 95% CI 0.78-0.92); there was no association between IBD and the middle ALAN level. High ALAN was associated with fewer IBD-specific outpatient visits (rate ratio [RaR] 0.93, 95% CI 0.86-0.99) and hospitalizations (RaR 0.83, 95% CI 0.72-0.95) 1 year after diagnosis. ALAN was not associated with surgery or emergency department visits. The association between ALAN and IBD is heterogeneous. Additional research is needed to understand how ALAN impacts IBD and identify other environmental exposures contributing to IBD etiology.
Per- and polyfluoroalkyl substances (PFASs), such as perfluorooctanoic acid and perfluorooctane sulfonic acid, are synthetic compounds that are persistent in the environment and are widely used in industrial and consumer products. Their bioaccumulative potential and pervasive human exposure have raised serious concerns about hepatotoxicity and carcinogenicity. This review thoroughly examines current epidemiological and experimental evidence linking PFASs exposure to an increased risk of liver cancer, particularly hepatocellular carcinoma. Epidemiological studies show higher PFASs levels in hepatocellular carcinoma patients, with notable sex-specific associations suggesting hormonal influences. Mechanistic studies indicate that PFASs disrupt lipid and bile acid metabolism, induce oxidative stress, cause epigenetic alterations, and activate key oncogenic pathways including peroxisome proliferator-activated receptor α, PI3K/AKT/mTOR, and necroptosis inhibition. Together, these effects collectively foster pro-tumorigenic microenvironment that promotes malignant transformation and proliferation. Despite growing evidence, significant knowledge gaps remain regarding PFASs effects on liver cancer, tumor immunity, and outcomes from mixed exposure. Future research should prioritize large-scale longitudinal studies, in-depth mechanistic investigations, and the development of targeted therapeutic and regulatory strategies to reduce PFASs-associated liver cancer risks.
Cannabis is linked with increased appetite, raising concern about obesity-related disease and type 2 diabetes. Yet data suggest metabolic benefits of cannabis through inflammatory processes and insulin sensitivity. This was a quasi-randomly assigned experimental study comparing acute effects of a CBD-dominant versus THC-dominant versus CBD + THC cannabis flower product. Data were collected from community participants through a mobile pharmacology laboratory and a clinical research center. Participants smoked their assigned pre-rolled cannabis flower cigarette ad libitum. Primary outcomes were IL-10, chemokine MCP-1, a composite of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-12, IFNG, and IL-4), and insulin sensitivity (Matsuda index). Outcomes were predicted by peak blood levels of THC and CBD immediately after cannabis use. Hypotheses were that inflammation and insulin sensitivity would vary as a function of CBD and THC exposure, and that inflammatory changes would be associated with insulin sensitivity. Participants (n = 108) were 25 to 45 (Mage = 29.7, sd = 5.4), 56.5% Female, and 88.0% white. Mixed effect models indicated a time X peak THC blood level interaction (B = 0.003, SE = 0.001, p = 0.037). As THC blood levels increased, inflammation increased more after acute use. There was a THC X CBD X time interaction on IL-10 (B=-0.001, SE = 0.000, p < 0.001). Higher than average peak blood THC was related to increasing IL-10 over time while lower than average peak THC was related to decreasing IL-10 over time but only at average or lower peak CBD levels. Cannabis use decreased MCP-1 acutely (effect for time: B=-48.757, SE = 15.061, p = 0.002), while there was no effect on the Matsuda Index. Acute cannabis use is associated with increases in both pro- and anti-inflammatory circulating cytokines, but not with insulin sensitivity. Additional research on the possible mediating mechanisms involved in the connection between cannabis use and type 2 diabetes is required.Trial registration: Gov NCT04114903, https://clinicaltrials.gov/study/NCT04114903, Registration date 11/08/2019.
Black soldier fly larvae (BSFL, Hermetia illucens) are increasingly used to convert organic wastes into insect biomass, yet their performance varies markedly among substrates. This variability limits the controllability of BSFL-based waste valorization systems. Conventional optimization efforts have largely emphasized macronutrient composition (e.g., protein and fat), while the effects of inorganic components and the physiological plasticity of the larvae have received little attention. To systematically elucidate the potential impact factors of this variability, we compiled and analyzed a global dataset comprising 905 rearing trials from 152 published studies. According to the results, high substrate ash content emerged as an overlooked constraint associated with reduced larval biomass and bioconversion efficiency. Larval performance was closely associated with the balance among substrate components. A Fat/Ash ratio >0.8 identifies as an empirical threshold associated with higher biomass accumulation, whereas a Protein/Fat ratio <2 was associated with higher bioconversion efficiency. We also observed a recurring trade-off between biomass accumulation and BSFL protein proportion. Under favorable conditions, larvae tended to prioritize biomass accumulation, whereas under stressful conditions, including ash-rich substrates, elevated temperature, and restricted feeding, they became smaller but maintained a relatively high body-protein proportion. Based on these statistical patterns, we propose an integrative framework linking substrate balance and larval physiological trade-offs. This framework summarizes empirical associations underlying performance variability and provides practical reference points for optimizing BSFL-based organic-waste-treatment systems.
Avian pathogenic Escherichia coli (APEC) is a major cause of colibacillosis in poultry, yet the role of the ecpA gene, which encodes the major structural subunit of the Escherichia coli common pilus (ECP), remains incompletely defined in APEC pathogenesis. To investigate the role of ecpA in the biological characteristics and pathogenicity of Avian Pathogenic Escherichia coli (APEC) strain FJLY68, an ecpA deletion mutant (ΔecpA) and its corresponding complemented strain (CΔecpA) were constructed using the CRISPR/Cas9 system and verified by PCR and Sanger sequencing. Phenotypic analyses revealed that the ΔecpA mutation significantly impaired bacterial motility, biofilm formation, adherence to chicken embryonic fibroblast (DF-1) cells, and fimbriae assembly. Transcriptomic analysis identified 1720 differentially expressed genes in the ΔecpA mutant, significantly enriched in pathways associated with flagellar assembly, chemotaxis, and metabolism, consistent with the observed phenotypic changes. Although in vitro growth was unaffected, the ΔecpA mutant exhibited markedly attenuated virulence in a chick infection model, as indicated by an increased LD50, attenuated clinical signs and pathological lesions, and reduced bacterial colonisation in tissues. Full genetic complementation restored all observed defects to wild-type levels. This study identifies ecpA as a critical determinant of APEC pathogenesis, directly linking its function to bacterial motility, biofilm formation, adhesion, and in vivo virulence, and provides a theoretical basis for developing novel control strategies targeting this virulence factor.
Cerebellar dysconnectivity has been repeatedly linked to psychosis and is often accompanied by disruptions in thalamic and cortical regions. These disturbances are broadly consistent with the triple network model, which conceptualizes psychopathology as arising from abnormal interactions among the salience (SAL), default mode (DMN), and executive control (ECN) networks. However, how the cerebellum interacts with thalamic and cortical components of these networks across different psychosis risk stages and early psychosis remains unclear. Resting-state functional MRI from 37 first-episode psychosis (FEP) patients, 63 clinical high-risk (CHR) individuals, 41 unaffected relatives (URs) of schizophrenia patients, and 100 healthy controls (HCs) were analyzed. The cerebellum and thalamus were parcellated according to their functional connectivity with cortical functional networks, and the DMN, SAL, and ECN subdivisions across all three regions were used to estimate cerebellar-cortical and cerebellar-thalamic connectivity across groups. Compared with HCs, FEP patients showed widespread increases in cerebellar-cortical connectivity across all three networks, together with reduced cerebellar-thalamic connectivity, most prominently within SAL-related circuits. CHR individuals exhibited predominantly increased connectivity, with localized disruptions across cerebellar, thalamic, and cortical regions. URs did not show significant connectivity differences relative to HCs. By extending the triple network framework to include cortico-thalamo-cerebellar pathways, this study characterized how cerebellar network connectivity differs across familial risk, CHR, and FEP groups. The observed pattern suggests that early changes in CTC circuits correspond to disruptions described within the triple network model, and highlights the potential relevance of cerebellar and thalamic involvement when characterizing network alterations across the psychosis spectrum.
Natural history collections are irreplaceable archives of global biodiversity, yet many remain affected by chemical contamination originating from historical conservation practices. Among these, mercury-based pesticides extensively used in herbaria continue to pose risks to human health, indoor air quality, and the accessibility of biodiversity collections. In this paper, we investigate the role of relative humidity (RH) in regulating gaseous elemental mercury (GEM) emissions from mercury-contaminated herbarium specimens, i.e. plant samples mounted on paper supports. We combined controlled laboratory experiments, using a non-steady-state flux chamber, with in-situ monitoring of GEM, temperature, and RH in the herbaria halls of the Natural History Museum of the University of Florence (Italy), hosting one of the world's most important botanical collections. Our results demonstrated a strong, non-linear dependence of GEM emissions on RH. Mercury fluxes from contaminated specimens were very low in dry conditions (30-60% RH) but increased exponentially at RH above c. 65%. In-situ herbaria halls monitoring confirmed that RH increases systematically coincide with higher GEM concentrations. These findings may suggest that moisture-driven physicochemical changes in cellulose-based materials strongly enhance mercury mobilisation and volatilisation. By explicitly linking microclimatic control to contaminant emissions, this study provides actionable evidence bridging scientific understanding and risk management in indoor environments. Maintaining low and stable RH (40-60%) emerges as a cost-effective strategy to reduce GEM emissions while preserving herbarium specimens. More broadly, our results highlight how environmental controls can mitigate chemical pollution in biodiversity repositories, supporting safer access to collections essential for ecological, taxonomic, and global change research.
Direct oral anticoagulants (DOACs) - dabigatran (a thrombin inhibitor) and rivaroxaban, apixaban, and edoxaban (factor Xa [FXa] inhibitors) - modify oxidative stress, endothelial inflammation, and barrier integrity beyond anticoagulation. We ask whether this reflects distinct pharmacology or silencing of proteases at protease-activated receptors (PARs), and propose a three-condition framework for when it becomes clinically measurable. Narrative review (PubMed, Scopus, Web of Science; primary search 2019-2026, with foundational earlier references retained) with claims graded on a six-tier hierarchy; A‡ marks trials formally negative or inconclusive owing to insufficient statistical power. DOAC effects largely converge on one node - reduced PAR-1 signalling under thrombin inhibition and dual PAR-1/PAR-2 blockade under FXa inhibition - rather than independent targets; the FXa-PAR-2 axis is cross-validated across macrophages, liver sinusoidal endothelial cells, and neutrophils; and dabigatran plausibly differs qualitatively rather than only in degree - a working hypothesis whose mechanistic linchpin (residual exosite-I signalling) currently rests on a single unreplicated in-vitro study (level D). Clinically the signal sorts by phenotype and disease phase, not class: low-dose rivaroxaban benefits stable atherosclerosis (COMPASS) but not heart failure in sinus rhythm (COMMANDER-HF), and COVID-19 benefit appears only in convalescence (MICHELLE), not acutely or in outpatients (ACTIV-4B, A‡). A nationwide cohort linked DOACs to lower acute kidney injury and chronic kidney disease progression than vitamin K antagonists, pending separation from their nephrotoxicity. Pleiotropy emerges where three conditions coincide - the protease is available at PARs, its generation is chronic, and PAR signalling is rate-limiting. This supports within-indication molecule selection (selection, not extension) and biomarker co-primary trials, not extension of indications.
To examine socioeconomic and demographic differences in who complains about healthcare and whether these factors are associated with the outcomes of complaint cases. Nationwide cross-sectional study in Denmark using linked national health, complaint and administrative registers. The Danish healthcare system provides universal coverage and has a centralised system for handling complaints with linked patient-level data to sociodemographic variables. All healthcare contacts in 2022 in general practice (GP), non-psychiatric hospitals and psychiatric hospitals were included. We examined two outcomes: (1) submission of a complaint and (2) whether the authorities upheld the complaint. We then assessed how these outcomes varied by socioeconomic position (SEP), focusing on the contrast between patients with the lowest and highest SEP profiles. Relative risks (RRs) were estimated using modified Poisson regression with cluster-robust variance estimation at the patient level. There were 31.9 million GP contacts, 4.8 million non-psychiatric hospital contacts and 345 000 psychiatric contacts, with 1381, 3545 and 439 complaints, respectively (0.43-12.7 per 10 000 contacts). Clear socioeconomic disparities emerged. Low-income patients were more likely to complain about GP and non-psychiatric hospitals, while higher education was associated with fewer complaints in these settings but more complaints about psychiatry. Patients outside the workforce were more likely to complain, whereas elderly patients were consistently underrepresented in the complaints.Low-SEP profiles had notably higher complaint probabilities than high-SEP profiles in GP (RR 2.60, 95% CI 2.22 to 3.70) and non-psychiatric hospitals (RR 1.69, 95% CI 1.40 to 1.98), but not in psychiatric hospitals (RR 0.93, 95% CI 0.47 to 1.38). Although individual SEP indicators showed no consistent differences in complaint outcomes, the combined SEP profiles revealed lower probabilities for complaints being upheld in lower SEP patients in GP (RR 0.58, 95% CI 0.22 to 0.94) and non-psychiatric hospitals (RR 0.70, 95% CI 0.43 to 0.96), while the estimate for psychiatric hospitals was inconclusive (RR 0.71, 95% CI 0.24 to 1.66). In this nationwide study, socioeconomic and demographic factors were linked to clear differences in both complaint submission and complaint outcomes. Except for psychiatric hospital services, patients with fewer socioeconomic resources were more likely to file a complaint yet had a lower probability of having it upheld. These findings point to disparities in who complains and in how complaints are assessed, and they underline the need to consider all complaints, regardless of outcome, when using complaint data to inform quality improvement efforts.
This study investigated the prevalence, genetic diversity, antimicrobial resistance, and virulence characteristics of Campylobacter spp. isolated from retail chicken carcasses in Beijing, China. Overall, Campylobacter was detected in 55.88% of samples, with significantly higher contamination in wet markets compared to supermarkets. A total of 106 non-duplicated isolates were obtained, including 59 C. jejuni and 47 C. coli, exhibiting high genetic diversity with 78 sequence types (STs) and 15 novel STs identified. Antimicrobial susceptibility testing revealed universal resistance to fluoroquinolones and high resistance to tetracycline, while multidrug resistance was prevalent, particularly in C. coli. Genotypic analysis identified 34 resistance genes and 4 point mutations, showing generally strong genotype-phenotype correlation, although notable discrepancies were observed, especially for florfenicol and azithromycin. The health risks to humans posed by tetracycline and macrolide-lincosamide-streptomycin (MLS)-associated antibiotic resistance genes (ARGs) should be given priority attention. Virulence profiling demonstrated that C. jejuni harbored significantly more virulence-associated genes than C. coli, including genes linked to Guillain-Barré syndrome, indicating a substantial potential public health risk from contaminated poultry.
Allelic variants in the leucine-rich repeat kinase-2 (LRRK2) gene are linked to Parkinson's disease, Crohn's disease and leprosy; however, a consensus role of LRRK2 in infection has not yet emerged. Parkinson's disease-linked p.G2019S mutation of LRRK2 results in increased kinase activity. We evaluated the impact of the p.G2019S mutation during the infection of mice with Salmonella typhimurium (ST) or Listeria monocytogenes. We demonstrate that the p.G2019S mutation promotes the phosphorylation of the p40phox and p47phox subunits of the NADPH oxidase-2 complex in the cytosol of neutrophils, leading to their relocation to lysosomes for enhanced bacterial control. Activation of Cathepsin B, Rab10 or PKC was not modulated by p.G2019S. Activation of the cytosolic subunits of NADPH oxidase-2 subunits was inhibited by the virulence factor SifA, which promotes the phagosomal localization of ST. Deletion of SifA resulted in an even greater effect of the p.G2019S mutation on the control of ST by neutrophils. These results suggest a mechanism by which the p.G2019S mutation promotes better control of infections at the cost of excessive tissue damage via NADPH oxidase-2 activity under chronic inflammatory conditions.
Branched-chain amino acid (BCAA) catabolism is controlled by the phosphorylation state of the branched-chain α-ketoacid dehydrogenase (BCKDH) complex, which is regulated by the opposing actions of BCKDH kinase (BDK) and the phosphatase PPM1K. Although fatty acids and amino acids both contribute to skeletal muscle energy metabolism, how fatty acid availability influences BCAA catabolic regulation remains incompletely understood. Here we examined the effects of lauric acid (C12), a medium-chain fatty acid abundant in dietary lipids, on BCAA metabolism in differentiated skeletal myotubes. Lauric acid increased phosphorylation of the BCKDH E1α subunit at Ser293 during nutrient perturbation in both mouse and human skeletal myotubes. Stable isotope tracing with U-[ˆ13C6]-leucine revealed that C12 reduced incorporation of leucine-derived carbon into downstream tricarboxylic acid (TCA) cycle-associated metabolites, indicating suppression of BCAA oxidative flux, whereas incorporation of labeled leucine into protein was not significantly altered. Mechanistically, genetic and pharmacological perturbation experiments indicated that the C12 effect requires PPM1K and is sensitive to O-GlcNAc cycling. Knockdown of O-GlcNAc transferase attenuated the C12-induced increase in BCKDH phosphorylation and reversed suppression of leucine-derived carbon flux. Dual-tracer experiments further showed that carbon derived from lauric acid and leucine converges in shared TCA cycle-associated metabolite pools, including glutamate and glutamine. Together, these findings identify a nutrient-sensitive regulatory node linking fatty acid availability, O-GlcNAc signaling, and BCKDH phosphorylation that modulates BCAA oxidation in skeletal myotubes.
Microbial aerosols from dental procedures pose a recognized yet unquantified airborne infection risk. During ultrasonic scaling, we performed multi-site sampling (saliva, air, surfaces) and combined metagenomics with quantitative 16S rRNA and ITS amplicon sequencing to profile viral, bacterial, and fungal communities. Using size-resolved aerosol sampling and absolute quantification, we determined the emission strength and size distribution of pathogenic bacterial aerosols (PBA), which were key inputs for computational fluid dynamics (CFD) simulations performed at ventilation velocities of 0.1, 0.2, and 0.4 m/s, corresponding to air exchange per hour (ACH) of 2.4, 4.7, and 9.4 h-1, respectively. We first linked patient oral microbiota to clinic aerosols, identifying a shared core of 51 viral, 55 bacterial, and 23 fungal families, of which three bacterial families (Streptococcaceae, Pasteurellaceae, Nocardiaceae) were pathogenic. The emission strength of PBA was ∼3.06×103 copies/min, with 66.7% concentrated in the 2.1∼4.7 μm fraction, a size associated with higher deposition in the lower respiratory tract. CFD simulations, fed with real pathogen concentrations and aerodynamic size spectra, revealed that increasing ACH from 0.1 to 0.4 m/s reduced PBA suspension (-26.4%) and surface deposition (-12.7%) during scaling, lowering the inhalation infection risk (IIR) at the dentist's position by 80.8% and keeping overall IIR below 25%. After scaling, lower velocity favours particle removal, supporting a dynamic ventilation strategy (high during treatment, low afterwards). This integrated framework provides a direct scientific basis for infection control in dental operatories.
The gut microbiome has been linked to major depressive disorder (MDD), yet it remains unclear whether antidepressant treatment influences these associations. This study aimed to clarify the role of serotonin reuptake inhibitors (SSRI/SNRI) in shaping gut microbiome changes observed in MDD. We conducted cross-sectional analyses in two independent patient cohorts (total N = 1802) and a meta-analysis across both cohorts, comparing the gut microbiome of MDD patients with and without SSRI/SNRI treatment. Here we show that SSRI/SNRI treatment is consistently associated with reduced Clostridium sensu stricto 1 abundance. This effect is specific to SSRI/SNRI treatment and not observed with other psychotropic medications. Importantly, reductions in Clostridium sensu stricto 1 in MDD compared to unaffected controls are explained by SSRI/SNRI medication status. Antidepressant treatment is an important factor shaping gut microbiome alterations linked to MDD, underscoring the need to account for medication effects and potentially informing future microbiome-based strategies to improve treatment response. This study examined whether commonly used antidepressants (called SSRIs and SNRIs) influence the gut microbiome in people with depression. The gut microbiome is a community of bacteria in the intestines that may affect mental health. We analyzed data from more than 1,800 people, including individuals with depression who were taking or not taking SSRIs and SNRIs. We found that people using these medications consistently had lower levels of gut bacterium called Clostridium sensu stricto 1. This effect was not seen with other psychiatric medications. This means we identified a bacterium that is influenced by antidepressant use. In the future, this knowledge may help test whether the gut microbiome can improve treatment outcomes and support more personalized care.
The functional properties of pectin are closely related to its molecular structure. In addition to the carbohydrate backbone, non-carbohydrate components such as intrinsic protein also play a significant role in influencing pectin properties both directly and indirectly. In this study, pepsin and papain were used to remove protein in high methoxyl pectin (HMP) extracted from citrus, achieving protein removal rates of 72.59% and 89.40%, respectively. Structural analyses from FTIR, XRD, and NMR confirmed that protein removal did not alter the fundamental functional groups of pectin. However, monosaccharide composition and atomic force microscopy (AFM) revealed that protein was linked to both the homogalacturonan (HG) and rhamnogalacturonan-I (RG-I) domains. Gel analysis showed that protein removal led to a 50°SAG reduction in gel strength at pH 2.5, whereas its impact at pH 6.0 was negligible. Additionally, the rheological characterization further demonstrated the positive role of protein in deformation stability in pectin gels.