Surgical bleeding remains a key determinant of morbidity in abdominoplasty and lipoabdominoplasty. While hormonal fluctuations during the menstrual cycle have been linked to altered hemostasis in hormonally responsive tissues such as breast and nasal mucosa, their impact on hormonally inert tissues like the abdominal wall remains unclear. This study prospectively evaluated whether menstrual phase influences perioperative bleeding in lipoabdominoplasty. A prospective, single-center study enrolled 90 women (18-55 years) undergoing standardized lipoabdominoplasty between January 2022 and January 2025. Patients with regular ovulatory cycles were stratified into three groups: perimenstrual (days 1-7, 21-28), periovulatory (days 8-14), and luteal (days 15-20). Exclusion criteria included coagulation disorders, hormonal therapy, anemia, smoking, and major prior abdominal surgery. Intraoperative blood loss was quantified by corrected suction volumes and gravimetric analysis of sponges; postoperative drainage was measured over 48 hours. Secondary endpoints included perioperative hemoglobin drop, drain removal time, and early complications. No significant differences were observed in intraoperative blood loss (480 ± 110 mL perimenstrual; 460 ± 105 mL periovulatory; 455 ± 115 mL luteal; p = 0.62) or postoperative drainage (p = 0.78). Hemoglobin decline, drain duration, and complication rates (seroma 6%, hematoma 4%, transfusion 1%) were comparable across groups. Correlation analysis showed that BMI and excised tissue weight, but not menstrual phase, were independent predictors of blood loss. These findings align with the hypothesis that the abdominal wall, supported by musculocutaneous perforators and stable dermal plexuses, is hormonally unresponsive and thus unaffected by cyclical endocrine changes. No statistically significant differences in bleeding or early outcomes were detected across menstrual cycle phases in patients undergoing lipoabdominoplasty. Surgical scheduling need not be adjusted based on menstrual timing, allowing cycle-independent planning without compromising safety. Larger multicenter studies with hormone assays may further refine these observations. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Cardiovascular disease (CVD) and cancer are the two leading health issues in the world, with CVD being the leading cause of death in all age groups and cancer, particularly prostate cancer (PCa), emerging as a significant concern among elderly men. Common risk factors like metabolic disorders, chronic inflammatory diseases, and hormone abnormalities have been theorized to be responsible for the increasing prevalence of these diseases. In this study, we examined the relationship between CVD and PCa, with emphasis on the pathophysiological events that connect them and how their coexistence affects patient outcomes. Common PCa treatments, such as androgen deprivation therapy (ADT) as well as androgen receptor signaling inhibitors (ARSI), have been linked to higher rates of hypertension, myocardial infarction, arrhythmias, and metabolic abnormalities. These cardiovascular side effects complicate the effective management of PCa, resulting in poorer overall results. It is essential to implement new integrated approaches to tackle these comorbid conditions. Recommendations include changes in lifestyle, personalized treatment plans, multidisciplinary collaborative efforts, and routine cardiovascular examinations for patients on PCa treatment. Evidence found that personalized exercise regimens and pharmaceutical treatments like statins and antihypertensives may lower cardiovascular risks and enhance outcomes in patients undergoing PCa treatment. Also, emerging technological interventions like wearable devices and telemedicine, such as smartwatches and mobile ambulatory blood pressure monitors (ABPMs), offer real-time cardiovascular monitoring and improve health outcomes among these patients. This study identifies the substantial gaps in clinical guidelines, notably in cardio-oncology integration, and emphasizes the importance of further research into biomarkers, shared inflammatory pathways, and individualized therapy methods. Hence, addressing these gaps will enable a more comprehensive approach to patient care, improving their quality of life and survival.
Menopause is a natural life stage with substantial impacts on women's quality of life and long-term health. Education on menopause for healthcare professionals (HCPs) remains limited and inconsistently embedded across health disciplines. This scoping review mapped current evidence on menopause education, including available programs, delivery approaches and extent of curricular integration. Following the Joanna Briggs Institute methodology and PRISMA-ScR guidelines, a search of six databases and gray literature (last searched May 2025) identified original research evaluating menopause-specific education for undergraduate and postgraduate HCPs. Data were synthesized using deductive and inductive analyses. Of 5034 records identified, 14 studies met the inclusion criteria: nine evaluated educational interventions and five examined curricular provision. Most studies originated from the USA and focused on medical residents. Education formats varied widely, including structured curricula, case-based learning, online modules, telemedicine encounters and peer-supported platforms. Core content commonly addressed menopause physiology, symptom management and hormone therapy, while long-term health implications and equity-focused content were infrequently included. Interventions consistently improved knowledge, confidence and preparedness for menopause care. Despite widespread recognition of its importance, menopause education remains inadequately integrated across healthcare training. Standardized, multidisciplinary and equity-focused menopause education frameworks are urgently required to strengthen clinical competence and improve care for midlife women. Menopause is a natural stage of life that can affect physical and mental health for many years, yet many healthcare professionals receive little formal training in how to support people during this transition. This can lead to delays in diagnosis, inconsistent advice and reduced access to effective treatments such as hormone replacement therapy (HRT).This study reviewed existing research to understand what menopause education is currently available for healthcare professionals, who receive this training and how it is delivered. We searched several international databases and included 14 studies that examined menopause education for doctors, nurses, pharmacists and other allied health professionals.Most studies were conducted in the USA and focused on doctors in training, particularly obstetrics and gynecology residents. Very few studies included nurses, pharmacists, physiotherapists, psychologists or general practitioners, despite their important roles in menopause care. Educational programs varied widely and included online learning, case-based teaching, clinic placements and peer-support networks.Overall, menopause education was found to be limited and inconsistent across healthcare training programs. However, when education was provided, it consistently improved healthcare professionals’ knowledge, confidence and ability to manage menopausal symptoms, including prescribing HRT. Only one study looked at whether learning was retained over time, suggesting that ongoing education may be necessary.This review highlights a need for better, more consistent and multidisciplinary menopause education for healthcare professionals. Improving training could help ensure that people experiencing menopause receive timely, accurate and supportive care across all healthcare settings.
What are the effects of integrating preimplantation genetic testing for aneuploidy into preimplantation genetic testing for monogenic/single gene disorders (PGT-M), termed 'comprehensive PGT' (coPGT-M)? A retrospective cohort of frozen embryo transfer cycles, derived from intracytoplasmic sperm injection, with single embryo transfers (SET) performed between 2019 and 2022 in patients undergoing their first round of assisted reproductive technology. CoPGT-M was implemented from July 2021. Only cycles with at least one biopsied blastocyst were included. Outcomes were compared between 701 embryos from 126 PGT-M cycles and 801 embryos from 131 coPGT-M cycles. The median female age at oocyte retrieval was similar between the PGT-M and coPGT-M cohorts [29.5 (IQR 27.0-33.0) versus 29.5 (IQR 28.0-33.0) years], as were male age, body mass index, and anti-Müllerian hormone concentration. The PGT-M cohort had a significantly lower median number of cumulus-oocyte complexes [15.0 (IQR 10.0-20.0) versus 15.5 (IQR 11.0-26.0); P = 0.039], while the number of zygotes, blastocysts biopsied, and blastocysts eligible for transfer after genetic analysis were comparable. The percentage of cycles resulting in at least one live birth (PGT-M 42.1% versus coPGT-M 51.9%) and the median number of embryo transfers required to reach the first live birth among patients who achieved a live birth [PGT-M 1 (IQR 1-2) versus coPGT-M 1 (1-2)] were comparable. Generalized estimating equation analysis, adjusted for embryo quality, showed higher odds of live birth per SET [adjusted OR (aOR) 1.86, 95% CI 1.21-2.87; P = 0.005] and lower odds of pregnancy loss (aOR 0.50, 95% CI 0.27-0.93; P = 0.028) in the coPGT-M cohort. While cumulative outcomes per cycle were similar, coPGT-M was associated with significantly higher odds of live birth per embryo transfer and lower risk of pregnancy loss, indicating clinical benefit, even in younger patients.
Patients with advanced or recurrent endometrial cancer who progress after platinum-based chemotherapy face a poor prognosis, and treatment options have historically been limited. The introduction of immunotherapy, alone or in combination with targeted agents, has substantially expanded therapeutic options in subsequent treatment lines. This study evaluated the efficacy and clinical benefit of second- and subsequent-lines of systemic therapy in a real-life cohort of patients with advanced or recurrent endometrial cancer. This retrospective, single-center analysis included patients treated at University Hospital Brno who were considered for second-line systemic therapy after failure of platinum-based chemotherapy between 2013 and 2024. Clinicopathological and molecular characteristics, systemic treatment modalities, best overall response, time to progression, and disease-specific survival were assessed. A total of 43 patients were identified; second-line treatment was initiated in 41 patients (95.3%). Of these, 26 (63.4%) received second-line chemotherapy, 14 (34.1%) received pembrolizumab alone or in combination with lenvatinib, and one patient (2.4%) received hormonal therapy. The median disease-specific survival for the entire cohort was 13.4 months (95% confidence interval 8.5-27.2 months). Among patients with re-administration of platinum-based chemotherapy, the median disease-specific survival was 27.2 months. Patients receiving pembrolizumab ± lenvatinib had a median survival of 23.4 months, whereas those treated with non-platinum chemotherapy had a median survival of 6.7 months. Two patients without active second-line treatment had a median disease-specific survival of 2.7 months. Nearly half of the patients treated with pembrolizumab ± lenvatinib experienced a prolonged time to progression compared with those receiving primary platinum-based chemotherapy. In patients with advanced or recurrent endometrial cancer after platinum failure, active systemic therapy may prolong survival and improve disease control. The greatest clinical benefit was observed with pembrolizumab alone or in combination with lenvatinib. An individualized, sequential approach to palliative systemic therapy is crucial to maximize clinical benefits.
The hormone vasopressin (AVP) controls renal water reabsorption by modulating the expression and trafficking of the water channel aquaporin-2 (AQP2) through the activation of the cAMP/PKA signal transduction pathway. Previous studies revealed that Olive Leaf Extract (OLE) counteracts the vasopressin-dependent AQP2 functions by stimulating the calcium-sensing receptor (CaSR). Here, the biological activities of p-Coumaric acid, a selective polyphenol in OLE, were investigated. Stimulation of renal collecting duct MCD4 cells with p-Coumaric acid at a concentration of 1 nM caused a significant intracellular calcium release. NPS-2143, a selective CaSR antagonist, abolished this increase. Molecular docking analysis revealed that p-Coumaric acid can form binding interactions with the binding pocket of Tecalcet, a known CaSR activator, likely suggesting that p-Coumaric acid may stimulate the CaSR. Confocal analysis and immunoblotting experiments showed that p-Coumaric acid impaired the DDAVP-dependent membrane expression of AQP2 and the consequent increase of the osmotic water permeability (Pf). Additionally, Fluorescence Resonance Energy Transfer (FRET) experiments demonstrated that p-Coumaric acid prevented the DDAVP-induced cAMP generation, consequently attenuating the AQP2 phosphorylation at serine 256. Together, these findings suggest that p-Coumaric acid may antagonize the effects of vasopressin, possibly by binding to and stimulating the CaSR.
The plant hormone abscisic acid (ABA) is vital for plant growth and response to environmental stresses. Nevertheless, detailed information regarding the EAR and PYR/PYL-PP2C-SnRK2 families, central components of the ABA signaling pathway, remains uncharacterized in Scaevola sericea, which is a salt-tolerant plant widely distributed in coastal areas. In our research, extreme salt stress induced ABA accumulation as well as changes in stress-responsive genes involved in ABA signaling transduction in leaves of S. sericea. Then, 5 SsEARs, 5 SsPYR/PYLs, 69 SsPP2Cs, and 7 SsSnRK2s genes were identified, and physicochemical properties and subcellular localizations were conducted. Further analysis showed that 3 SsEARs, 2 SsPYR/PYLs, and 39 PP2Cs genes were significantly altered by NaCl treatment and had various correlations with accumulated ABA contents. Arabidopsis transgenic lines overexpressing SsPYR1 exhibited reduced ABA tolerance; overexpression of SsEAR4 and SsEAR5 alleviated ABA sensitivity but showed complicated performance to salinity; SsPP2C14 and SsPP2C26 genes significantly enhanced plants' resistance to ABA and salt stimulation, evidenced by seed germination, seedling growth, and root elongation. Y2H and LCI assays imply that SsPYR1/SsEAR4 interacts with SsPP2C14 and SsEAR1/SsEAR3 interacts with SsPP2C26. Further studies verified that the accumulated SsPP2C14 and SsPP2C26 triggered by salt treatment limited ABA-responsive gene expressions but promoted salt-responsive gene expressions and thereby enhanced the adaptations of Arabidopsis to adverse stress. This study enhances our understanding of the SsEAR, SsPYR/PYL, and SsPP2C gene families in S. sericea and offers valuable gene resources that could be helpful to engineer salt-tolerant plants for ecological restoration.
This study evaluated if [99mTc]HYNIC-prostate-specific membrane antigen (PSMA)-11 scintigraphy presents a clinically viable imaging alternative to [68Ga]PSMA-11 PET/computed tomography (CT) for disease evaluation in prostate cancer (PC). In this prospective study, 106 patients diagnosed with prostate cancer were recruited. A total of 51 patients were assigned in the initial staging cohort and the remaining 55 patients in the re-staging cohort (comprising biochemical recurrence, metastatic castration-resistant prostate cancer, and metastatic hormone-sensitive prostate cancer). Imaging with [99mTc] HYNIC-PSMA-11 was conducted within one week following [68Ga]PSMA-11 PET/CT. Whole-body planar [99mTc]HYNIC-PSMA-11 images were obtained at 2-, 4-h, and regional SPECT/CT at 3-h. A comparative detection efficiency of [99mTc]HYNIC-PSMA-11 versus [68Ga]PSMA-11 PET/CT was evaluated by consensus for the involved lesions/sites. A correlation analysis was carried out between maximum standardized uptake values of PSMA PET and percent quantitative lesion uptake values of PSMA SPECT. [68Ga]PSMA-11 PET/CT detected 896 metastatic lesions, where HYNIC-PSMA-11 detected 761 lesions, offering an overall sensitivity of 85%. The sensitivity of [99mTc] HYNIC-PSMA-11 SPECT/CT was 100% for primary/visceral lesions, 92% for skeletal lesions, 75.3% for distant lymph nodes and 67.4% for locoregional lymph nodes. A substantial agreement (κ = 0.78, P < 0.0001) was seen between two imaging modalities. UCSF Cancer of the Prostate Risk Assessment score based disease staging matched with the disease staging demonstrated by both the imaging techniques. A significant (P < 0.01) correlation was seen between the quantitative parameters of the two techniques both for primary (r = 0.96) and metastatic (r = 0.79 for skeletal and r = 0.65 for lymph nodes) lesions. [99mTc]HYNIC-PSMA-11 SPECT/CT offers a potentially viable and cost-effective substitute for PSMA-PET for disease staging, quantification and response assessment to PSMA-targeted radiotherapies.
Circulating tumor DNA (ctDNA) genomic testing is increasingly used in advanced prostate cancer (aPC) to identify actionable alterations, however the longitudinal nature of tumor mutation burden (TMB) remains poorly characterized. Current guidelines recommend somatic testing at diagnosis of metastatic hormone-sensitive or castration-resistant disease, but do not address serial testing. While prior studies suggest modest increases in TMB with advanced disease, longitudinal trends and treatment-associated changes have not been systematically examined. Here we evaluate how TMB changes over time and in relation to treatment exposures in a large real-world aPC cohort. We retrospectively identified 714 men with aPC who underwent ≥ 1 ctDNA-based genomic profiling test with evaluable TMB between November 2018 and May 2025. For patients with multiple tests, sequential TMB values were mapped to discrete treatment episodes, used as a surrogate for lines of therapy. Univariable linear mixed-effects models with fixed effects for timeframe and treatment exposures, and random intercepts for repeated measurements, assessed associations between TMB, episode number, age, individual therapies, and treatment combinations. An exploratory multivariable mixed-effects model was also performed. Median age at diagnosis was 63.3 years (interquartile ranges [IQR] 56.8-69.0); median prostate specific antigen 13.9 ng/mL (IQR 6.8-60.9). Median first-test TMB was 7.8 mutations per megabase (mut/Mb) (IQR 4.8-11.2). TMB increased significantly across episodes (P = .001). Age was associated with higher TMB (+ 0.20 mut/Mb per year, P < .0001). In univariable analyses, radiotherapy (RT) was associated with higher TMB (+ 1.9 mut/Mb, P = .004). In multivariable models adjusting for age and treatment episode, RT remained associated with higher TMB (+ 2.4 mut/Mb, 95% confidence intervals 1.1-3.7; P = .0004). Combination regimens, particularly androgen deprivation therapy + androgen receptor pathway inhibitors + RT, were associated with marked increases in absolute TMB. We demonstrate that TMB is dynamic and rises over time and with select treatment exposures. These findings reinforce how TMB should be interpreted within the broader context and not necessarily viewed as a standalone threshold for initiating immunotherapy in advanced prostate cancer.
The traditional Chinese medicine Salvia miltiorrhiza is widely used in the treatment of cardiovascular diseases due to its rich of phenolic acids and tanshinones. Among S. miltiorrhiza from different producing areas in China, the Sichuan ecotype (S. m.-SC) has the highest accumulation of phenolic acids, while the lack of tanshinones content seriously restricts its quality and downstream industrial development. It is urgent to develop the quality improvement cultivation technology and explore the regulation mechanism of tanshinone biosynthesis. Herein, we systematically evaluated the interaction between exogenous hormones and tanshinone accumulation in S. m.-SC, and found that Methyl jasmonate (MeJA) could significantly increase the accumulation of tanshinones in S. m.-SC. Based on the integration of pan-transcriptome datasets led to the construction of a tanshinones core metabolic regulatory network and SmMYC3 is a novel discovered positive regulator of tanshinone biosynthesis following SmMYC2a/2b. Yeast one-hybrid (Y1H) and Dual-LUC experiments showed that SmMYC3 directly binds to the G-box elements in the promoters of tanshinone biosynthesis genes (SmGGPPS1, SmKSL1, and SmCYP76AH1). Unexpectedly, SmMYC3-SmMYC2b/SmMYC3 complex identified via yeast two-hybrid (Y2H), Bimolecular fluorescence complementation (Bi-FC) and Dual-LUC experiments has robust enhance the transcriptional activation of the tanshinone metabolism genes upon the involvement of MeJA signaling. This work further expanded the molecular network of MYC transcription factor regulating tanshinone metabolism, clarified the regulatory mechanism of tanshinone biosynthesis mediated by MeJA, and drew a new blueprint for the application of MeJA in the increase of tanshinone content in S. miltiorrhiza.
Male infertility is a multifactorial condition often linked to oxidative stress and apoptosis. Key molecular regulators, such as NRF2 (antioxidant defense) and p53 (cell cycle and apoptosis), are influenced by hormonal and inflammatory pathways; however, their combined role in infertility remains underexplored. This study investigates the integrated expression of NRF2 and p53 genes and their association with hormonal, inflammatory, and biochemical markers in infertile males. A case-control study was conducted on 300 males (150 infertile, 150 fertile controls). Gene expression (NRF2, p53) was analyzed using RT-PCR. Hormonal (FSH, testosterone, estradiol), inflammatory (IL-6), and biochemical (SOD, PSA) markers were measured via ELISA. Statistical analysis included t-tests, ROC, scatter plot, and multiple regression. Infertile men showed significantly reduced NRF2 expression and SOD levels, with elevated FSH, estradiol, IL-6, PSA, and p53 expression (p<0.001). ROC analysis identified FSH and NRF2 as strong predictors of infertility. Regression revealed IL-6 and PSA as significant positive predictors of p53 expression, while SOD positively correlated with NRF2. Scatterplots highlighted contrasting biomarker associations for NRF2 and p53. Combined dysregulation of NRF2 and p53, driven by oxidative, hormonal, and inflammatory factors, plays a critical role in male infertility. These genes hold promise as both diagnostic biomarkers and therapeutic targets.
The populations of native roosters exhibit a reduced capacity for reproduction because of thermal stress, which adversely influences the quality of semen and the production of sperm. Nutritional strategies using natural bioactive compounds may boost male reproductive function, with silkworm pupae as a high-quality protein source and fingerroot containing antioxidant phytochemicals This study evaluated the effects of oral silkworm pupae and fingerroot extract on semen quality, fertility, testicular histology, and serum testosterone. Roosters were randomly assigned into three groups: control, silkworm pupae-supplemented (500 mg/day), and fingerroot-supplemented (500 mg/day). Proximate analysis revealed silkworm pupae is rich in protein (53.7%) and lipids (32.1%), while fingerroot exhibited high antioxidant activity through phenolics and flavonoids. Results demonstrated significant improvements (P < 0.05) in progressive sperm motility (68.54 ± 1.33%) and testosterone levels (6.86 ± 1.38 ng/mL) in the silkworm pupae group compared to controls. Fingerroot supplementation significantly increased sperm concentration (3.89 × 10⁹ sperm/mL; P < 0.05). Furthermore, silkworm pupae improved seminiferous tubule width, germinal epithelial growth, and spermatogenic activity, with significantly higher testosterone levels compared to the control group (2.21 ± 0.51 ng/mL; P < 0.05). In conclusion, silkworm pupae and fingerroot extract effectively improved semen quality and testosterone levels in Thai native roosters. These findings highlight their potential as promising natural dietary supplements to enhance reproductive performance in sustainable indigenous poultry farming.
Chemically similar metal(loid)s exploit nutrient transport systems and destabilize integrated metal-homeostasis networks, triggering redox imbalance, transcriptional reprogramming, and multiscale regulatory responses that ultimately determine plant adaptation or toxicity. Plant growth depends on the homeostasis of mineral nutrients, but it is short in heterogeneous soils where required elements are found together with chemically similar harmful metal(loid)s. The divalent ionic and coordination properties of Cd-Zn and Ni-Fe are similar, while the arsenate-phosphate interactions are structurally analogous oxyanion mimicry systems. Cd-Zn, Ni-Fe, and As-P have broad-substrate transport systems with partially overlapping ion-recognition properties, notably under nutrient-limiting conditions. Although it is widely recognized that transporter promiscuity exists in a systemic manner. The overall systemic effects, such as metal homeostasis, redox signaling, activity of the organelles, transcriptional regulation, and whole-plant ion balance between tissues and cellular compartments of its action, are not yet clearly understood. We are stating that chemically similar metal stress signifies the destabilization of an integrated homeostatic network and not just limitation of transporters. Substantial overlap exists in conserved transporter families (ZIP, NRAMP, PHT, IRT, HMA), which are triggered by nutritional deprivation to induce high-affinity transporter families, which stimulates the uptake of both essential and simultaneously detrimental metals. Competitive metal entry causes disruption of the cytosolic and organellar redox balance, leading to the production of ROS, which results in transcriptional reprogramming, turnover of transporters, metal redistribution, and calcium-, kinase-, and hormone-mediated signaling. In addition to uptake, intracellular regulatory mechanisms act to control metal partitioning, including thiol chelation, vacuolar sequestration, metallochaperone activity, organelle-specific redistribution, and transporter dynamics. Root exudation and plant-microbe interactions are some of the rhizospheric activities that cause further speciation of the metals before they can enter the membrane. We suggest a multiscale model, in which coordinated regulatory reprogramming during co-exposure is the basis for adaptive resistance, and failure of metal homeostasis, and redox-feedback regulation is the basis for toxicity. Chemical mimicry can therefore be considered a systemic limitation of the productivity of plants.
Sexual hormone receptors (SHRs) are essential for breast cancer (BCa) pathogenesis. BCa is a prevalent malignancy with high heterogeneity and high recurrence. Endocrine resistance remains a major clinical challenge. SHR-mediated transcription involves complex epigenetic, post-translational, and inter-receptor crosstalk, and dysregulation of these processes contributes to endocrine resistance. This review aims to summarize the current progress on the molecular mechanism underlying the function of nucleic SHRs in BCa, providing insights for the novel therapeutic strategies in BCa.
This study assesses the stress-related impacts of the construction of the Thwake Multipurpose Dam in Makueni, Kenya by examining salivary cortisol concentrations and patterns of diurnal variation. One set of evening, waking, and 30-min post-waking saliva samples was collected across 221 women who were displaced by the dam or who lived upstream or downstream of the dam development site. Salivary cortisol concentration was analyzed using a commercially available assay kit. Multivariable linear regression was used to assess the relationship between displacement status and waking cortisol concentration, evening cortisol concentration, cortisol awakening response, and diurnal difference. Log-transformed evening cortisol concentration (displaced: β = 0.365, p = 0.018; downstream: β = 0.675, p = 0.007) and diurnal difference (displaced: β = 0.034, p = 0.049) were significantly associated with displacement status. Both displaced and downstream communities demonstrate stress-related hormonal differences associated with dam-induced disruption. Future policy and research addressing the health impacts of hydroelectric dam development should include downstream communities in addition to those directly displaced by development.
'Candidatus Liberibacter asiaticus' (CLas), the causal agent of citrus huanglongbing, is transmitted by the Asian citrus psyllid Diaphorina citri. While CLas-positive (CLas+) females exhibit increased fecundity and metabolic demands, their neuroendocrine regulation mechanisms remain unclear. We propose CLas manipulates dopamine (DA) signaling to enhance psyllid fecundity and CLas proliferation. Metabolomics revealed elevated DA in CLas+ females. Silencing DA synthesis genes and receptor DcDop2 via RNAi reduced lipid reserves, fecundity, and ovarian CLas titers. Through combined in vivo and in vitro experiments, we demonstrated that the microRNA miR-31a suppresses DcDop2 expression by binding to its 3' untranslated region. Overexpression of miR-31a resulted in decreased DcDop2 expression and CLas titers in the ovaries, eliciting phenotypic defects akin to DcDop2 knockdown. Furthermore, DcDop2 knockdown and miR-31a overexpression reduced juvenile hormone (JH) levels and adipokinetic hormone (AKH) signaling in fat bodies and ovaries. Consequently, CLas regulates the DA-DcDop2 signaling axis to improve D. citri lipid metabolism and fecundity, while simultaneously promoting its replication. These findings reveal a coevolution between CLas proliferation and ovarian development in the insect host. This discovery enhances our understanding of the molecular interplay between plant pathogens and vector insects and offers novel targets and strategies for HLB field management.
This review synthesizes recent advances and develops an integrative regulatory framework that links shoot apical meristem size control to tomato fruit locule number, encompassing genetic, phytohormonal, and environmental determinants. Tomato is a globally vital vegetable crop that contributes significantly to human nutrition and agricultural economies. The number of locules, a key component of fruit morphology, is a primary determinant of ultimate fruit size and shape, thereby influencing both market yield and consumer preference. This review focuses on how shoot apical meristem size control acts as a core hub that connects genetic, hormonal, and environmental cues to the regulation of tomato fruit locule number. We synthesize recent progress in understanding the molecular and physiological mechanisms behind locule determination, with a particular focus on integrative networks linking known regulators. By bridging insights from these interconnected domains, we aim to present a more holistic view of the developmental process. Furthermore, we propose avenues for future research aimed at achieving a deeper understanding of the modulation mechanisms that govern fruit locule formation and their numerical count in this vital crop.
This study estimated FRAX®-based intervention thresholds for initiating osteoporosis treatment in Chinese postmenopausal women, using real-world data from the largest nationally representative osteoporosis survey in China and a validated Markov microsimulation model. Denosumab became cost-effective at a 10-year major osteoporotic fracture probability of 7%, and zoledronate at 12%, whereas alendronate and teriparatide did not reach cost-effectiveness at any FRAX probability evaluated. To determine drug-specific FRAX® thresholds for cost-effective initiation of osteoporosis treatment (alendronate, zoledronate, denosumab, teriparatide) in Chinese postmenopausal women using real-world data. A validated Markov microsimulation model was used to simulate lifetime costs and quality-adjusted life years (QALYs) of no treatment versus alendronate, zoledronate, denosumab, and teriparatide treatment. Baseline patient characteristics and risk factor distribution were sampled from the largest national osteoporosis survey in mainland China. The analysis was conducted from the societal perspective, applying a willingness-to-pay threshold of USD 13,000 per QALY gained (equivalent to one times China's GDP per capita). Denosumab was cost-effective at a 10-year major osteoporotic fracture probability of 7% and zoledronate at 12%; neither alendronate nor teriparatide became cost-effective. For denosumab, the cost-effective threshold of 10-year major osteoporotic fracture probability increased with age from 51 to 65 years and then declined in older women, ranging from 5 to 12%. For zoledronate treatment, the cost-effective thresholds of a 10-year major osteoporotic fracture probability were 8% at 51-55 years, 12% at 71-75 years, and 8.5% at 76-80 years. For Chinese postmenopausal women, denosumab was the most cost-effective treatment, while zoledronate also reached favorable thresholds in selected age groups. Implementing drug-specific FRAX®-guided thresholds may optimize treatment decisions for osteoporosis and support efficient healthcare resource use.
Intensive care unit-acquired weakness (ICU-AW) is a common complication among critically ill patients. Existing evidence indicates that critically ill patients frequently develop low triiodothyronine syndrome (LT3S), and this thyroid hormone imbalance may disrupt muscle metabolic pathways and thereby promote the onset and progression of ICU-AW. However, the relationship between FT3 levels and ICU-AW remains inconclusive, and clinical research addressing this link remains limited. Accordingly, this study aims to examine the clinical relationship between FT3 levels and ICU-AW. We enrolled patients with mechanical ventilation in the ICU of the Second Affiliated Hospital of Harbin Medical University from June 2024 to December 2025, dividing them into low-T3 group (n=46, FT3<2.43pmol/L) and non-low T3 group (n=33, FT3≥2.43pmol/L) by admission FT3 levels. ICU-AW was defined as a Medical Research Council score≤48. We collected clinical data including demographics, comorbidities and laboratory results, compared baseline characteristics, and adopted correlation, regression and subgroup analyses to assess relevant associations. Among 79 patients, 58.2% had reduced admission FT3, and its incidence decreased with increasing MRC scores. Spearman analysis showed FT3 levels were positively correlated with MRC scores. Fully adjusted logistic regression confirmed FT3 as a factor associated with ICU-AW (OR=0.31; 95% CI, 0.10-0.97; p=0.0447). ROC analysis indicated FT3 had good discrimination for ICU-AW (AUC=0.84). Reduced FT3 levels are closely associated with the development of ICU-acquired weakness, with higher FT3 levels showing a positive correlation with higher MRC scores and a negative correlation with the risk of ICU-AW. The study has been registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2500100201, registration date: April 3, 2025). This study is a retrospective registration.
Orthodontically induced inflammatory root resorption (OIIRR) is a common complication of orthodontic therapy, characterized by sterile inflammatory degradation of dental hard tissues on the root surface. Its pathogenesis involves complex interplay of biomechanical forces and molecular pathways within the periodontal microenvironment. Key mechanisms include inflammatory signaling via IL-6, IL-1β, and IL-18, mechanotransduction through Piezo1 and sphingosine-1-phosphate (S1P), cell-to-cell communication via exosomes and ligand-receptor interactions, and disruptions in osteogenic pathways including Wnt/β-catenin and EphB4/ephrinB2. Programmed cell death (pyroptosis, ferroptosis), mitochondrial dysfunction, autophagy, and post-transcriptional regulation by non-coding RNAs further contribute to osteoclast differentiation. Current predictive strategies focus on biomarkers in gingival crevicular fluid (GCF). Therapeutic interventions under investigation include anti-inflammatory agents, low-intensity pulsed ultrasound, laser and photobiomodulation (PBM) therapy, and bioactive substances such as lithium chloride (LiCl), exosomes, and intermittent parathyroid hormone (iPTH). Prognostically, mild to moderate OIIRR rarely compromises long-term tooth survival, whereas severe resorption requires individualized risk assessment. Notably, endodontically treated teeth exhibit significantly less OIIRR than vital pulp teeth, as root canal therapy eliminates pulp-derived pro-resorptive signaling (CH25H/25-HC, NF-κB, MMPs), offering a clinically relevant strategy for high-risk cases. This review synthesizes current knowledge on OIIRR mechanisms and emerging treatments, providing a framework for prevention and targeted therapy.