Conectar
by Guohui Wang, Lu Liu, Hanshu Zhang, Panpan Mao, Saijuan Lu, Xiaofang Zhang, Xingde Li, Cangsang Song
BackgroundLiver transplantation (LT) is an effective treatment for patients with end-stage liver disease. In recent years, more and more evidence has supported the association between gut microbiota dysbiosis and the pathogenesis and progression of liver diseases.
MethodsThe study included 36 patients who received tacrolimus treatment after liver transplantation. Patients were stratified into subgroups according to three key variables: tacrolimus treatment duration, whole-blood tacrolimus concentration, and tacrolimus concentration-to-dose (C/D) ratio. Fecal samples and whole-blood specimens were collected from all participants. The Illumina HiSeq X platform was used to detect the gut metagenome, analyzing the composition and characteristics of the gut microbiota. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology was employed to detect metabolites of the gut microbiota, revealing their metabolic profiles.
ResultsAs the duration of tacrolimus use increased, the diversity of the gut microbiota also increased, and the abundance of Escherichia coli_D and Bacteroides stercoris rose. Additionally, the abundance of Brunovirus and Uetakevirus tended to decrease. The abundance of gene functions related to chemical carcinogenesis and bacterial invasion of epithelial cells significantly decreased. In the gut microbiota metabolites, 16 substances like Astragaloside A and Acetyl-L-carnitine significantly increased, while 108 substances like Capsaicin and TLK significantly decreased. Within a certain range, as the concentration of tacrolimus in whole blood increased, the diversity of the gut microbiota increased. The abundance of Phocaeicola and Klebsiella increased, and the abundance of Peduovirus among viruses also rose. However, excessively high concentrations may lead to a decrease in the diversity of the gut microbiota and a decrease in the abundance of Phocaeicola. With respect to the C/D ratio, increased ratios were linked to significantly higher levels of 57 fecal metabolites (e.g., PC 34:2, 5-Methyl-2’-deoxycytidine), whereas 13 metabolites (e.g., FAHFA 2:0/16:0) showed substantial declines.
ConclusionsTacrolimus treatment is associated with distinct alterations in gut microbiota and metabolites among LT recipients. These findings provide a preliminary framework for future investigations aimed at optimizing immunosuppressive regimens, although their clinical translational potential requires validation in larger-scale, prospective cohort studies.
by Zijing Wang, Liyuan Ma, Zhanyuan Sun, Hengyi Lv, Ruxue Ma, Mengqi Ding, Hai Li, Tao Jiang
BackgroundDiethyl phthalate (DEP), a widely used plasticizer with endocrine-disrupting properties, has raised concerns regarding its potential carcinogenic effects. However, its precise role in colorectal cancer (CRC) development remains poorly understood.
MethodsThe chemical structure of DEP was obtained from the PubChem database. Potential targets of DEP were identified through ChEMBL and STITCH databases and intersected with known CRC-related genes to screen for candidate biomarkers. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the biological functions and signaling pathways involved. Molecular docking was conducted to predict the binding affinities between DEP and core targets. Finally, 200-ns molecular dynamics (MD) simulations using GROMACS were employed to evaluate the binding stability and dynamic behavior of the DEP–target complexes.
ResultsA total of 62 overlapping genes were identified between DEP targets and CRC-associated genes. GO and KEGG enrichment analyses indicated enrichment in epigenetic regulation, chromatin remodeling, and cancer-related signaling pathways, including Notch, TGF-β, and FoxO. Protein–protein interaction analysis identified EP300, EZH2, HDAC1, HDAC2, and KDM1A as key epigenetic regulators. Molecular docking predicted moderate binding affinities between DEP and these targets (−6.6 to −5.7 kcal·mol ⁻ ¹). Subsequent 200-ns MD simulations suggested that DEP formed stable complexes with HDAC1, KDM1A, and EZH2, moderate stability with EP300, and partial dissociation with HDAC2, consistent with hydrophobic and hydrogen-bonding interactions at the binding interfaces.
ConclusionThis study provides a theoretical framework for exploring the molecular mechanisms through which DEP may contribute to CRC development, emphasizing the value of network toxicology in cancer research. These findings may inform future investigations into the risks of DEP exposure and support public health policy and the development of targeted therapeutic strategies.
by Yu Wang, Filzani Illia Ibrahim, Junlin Chang, Siti Norzaini Zainal Abidin
The issue of stress among urban residents is becoming increasingly serious, affecting both physical and mental health in cities in China. Pocket parks serve as essential green spaces for people’s well-being in high-density urban environments. However, limited empirical research has examined how plant landscape components support stress recovery among urban residents, particularly in the context of pocket parks in China. This study investigated the effects of plant species richness and plant landscape types on stress recovery, with a focus on the mediating role of perceived aesthetic quality. A pre-test and post-test design were conducted in six selected pocket parks with different landscape characteristics using questionnaire surveys. A total of 605 urban residents were recruited using a random sampling method at different sites. The results indicated that medium plant species richness (t = −10.502, p pby Hongfei Yang, Chao Sun, Ya Li, You Zhou, Rui Wang, Yingxue Li
ObjectiveThe triglyceride-glucose index and estimated glucose disposal rate serve as notable surrogate markers of insulin resistance, demonstrating established links to cardio-cerebrovascular disease. However, their combined prognostic value in predicting cardio-cerebrovascular disease outcomes remains unexplored. The current investigation examined the interaction between the TyG (triglyceride–glucose index) index and eGDR (estimated glucose disposal rate) concerning the danger of cardiovascular disease within a clinical population.
MethodsThis investigation employed data sourced from the China Health and Retirement Longitudinal Study (CHARLS). The median TyG index and eGDR scores were used to stratify the participants into 4 categories: low TyG/high eGDR, high TyG/high eGDR, low TyG/low eGDR, and high TyG/low eGDR. Clinical characteristics across groups were systematically compared. Cox proportional hazards regression models evaluated the distinct and interconnected associations of the TyG index and eGDR with the risk of cardio-cerebrovascular disease, with multiplicative and additive interaction effects subsequently assessed through formal interaction analysis.
ResultsThe final study cohort comprised 7,330 participants, with 1,336 individuals (18.2%) developing cardio-cerebrovascular disease during the 9-year follow-up. Stratification using median thresholds (TyG: 8.59; eGDR: 10.55 mg/kg/min) yielded four groups: low TyG/high eGDR (n = 2,991), high TyG/high eGDR (n = 1,375), low TyG/low eGDR (n = 1,372), and high TyG/low eGDR (n = 2,292). Multivariable-adjusted Cox regression analyses revealed markedly increased risks of cardio-cerebrovascular disease among the various exposure groups when contrasted with the low TyG/high eGDR reference: high TyG/high eGDR (HR: 1.31, 95%CI: 1.10–1.57, ppp Conclusion
The TyG index and eGDR demonstrate independent associations with cardio-cerebrovascular disease risk, while their combined assessment reveals synergistic predictive capacity. Combined assessment of the two allows for further accurate stratification of the population based on insulin resistance and improved prediction of cardio-cerebrovascular disease.
by Lin Zhang, Feng Luo, Yalin Chai, Lijie Sun, Xuan Wang, Le Yin, Congjuan Luo
Acute kidney injury (AKI) remains a major clinical challenge due to its high morbidity and mortality, with ischemia-reperfusion injury (IRI) as one of its primary causes. Severe IRI-associated AKI (IRI-AKI) can progress to irreversible renal failure, yet no effective therapies are currently available. Ferroptosis, an iron-dependent regulated cell death, has recently been implicated in the pathogenesis of IRI-AKI. Moreover, IL-22 may alleviate AKI by modulating the ferroptosis process through regulation of the P62-Keap1-Nrf2 signaling axis. In this study, we examined the protective role of the immune cytokine interleukin-22 (IL-22) in IRI-AKI and its mechanistic association with ferroptosis. Using a murine IRI model and an HK-2 cell hypoxia/reoxygenation system, we systematically assessed the impact of IL-22 treatment. IL-22 administration significantly enhanced renal function, reduced histological injury, and limited both reactive oxygen species accumulation and ferroptotic cell death. Further mechanistic studies demonstrated that IL-22 suppresses ferroptosis in vitro through an Nrf2-dependent mechanism and is associated with activation of the P62-Keap1-Nrf2 signaling pathway. These findings offer experimental evidence supporting IL-22 as a potential therapy for IRI-AKI and highlight ferroptosis modulation as a promising therapeutic strategy.by Chunqing Yang, Qingjie Xue, Yu Feng, Wenjun Ding, Ying Lu, Qinqin Wang
Conventional dendritic cells (cDCs) are pivotal antigen-presenting cells (APCs) with critical roles in immune regulation, yet their subset classification remains ambiguous due to phenotypic overlap with macrophages and monocytes, particularly in the spleen. This study employed multi-parametric flow cytometry and clodronate liposome (CL) depletion to systematically re-evaluate splenic CD11chighMHCIIhigh cDCs in C57BL/6 mice. We identified three novel subsets: (1) a tissue-resident T-cell zone macrophage (TZM)-like population (F4/80inter-lowCX3CR1+MERTK+) constituting 0.59% of cDC2s with >10-fold CL-depletion resistance (p high APC subset (CCR2 ⁻ Ly6C⁻) accounting for 2.7% of cDC2s with CL-sensitivity; (3) unconventional CD4⁺CD8α⁺ hybrids present in 2.57% of cDC2 and some cDC1s. These findings demonstrate unprecedented cDC plasticity driven by microenvironmental signals, revising conventional classification frameworks and proposing new targets for DC-based immunotherapies in autoimmunity and cancer. Our phenotypic mapping provides a foundational framework for future functional investigations into these novel subsets.by Li Dong, Changkun Ma, Wanghai Tao, Quanjiu Wang
The flow characteristics of water and gas are closely linked to pore structure of porous media, which is of critical importance across various scientific and industrial fields. In this study, synthetic porous media with varying grain sizes and porosity were generated, and their corresponding pore structures were characterized using pore network modeling. Furthermore, the intrinsic permeability, water retention curve, water-gas relative permeability and relative gas diffusivity of the synthetic porous media were simulated via pore network modeling. The results demonstrate that the pore networks extracted from images can effectively distinguish pore structural characteristics. Specifically, the mean pore diameter, throat diameter, and throat length were larger in coarse-grained media compared to fine-grained media of the same porosity. In contrast, fine-grained media exhibited higher values for pore number, throat number, and coordination number. Additionally, the distributions of pore diameter, throat diameter, throat length and coordination were found to follow a lognormal distribution. Porous media with coarse grains and larger porosity exhibit greater intrinsic permeability and relative gas diffusivity compared to media composed of finer grains or lower porosity. The water-retention curves were fitting by van Genuchten model, revealing an exponential relationship between parameter α and throat diameter (or pore diameter). But the parameter n did not show a clear trend across various synthetic porous media, which is attributed to the relatively narrow range of pore size distribution. Similarly, for water-gas relative permeability, the critical water saturation did not vary significantly across different porous media. A strong correlation was observed among the pore structural parameters, irrespective of grain shape and size. Both intrinsic permeability and relative gas diffusivity exhibited a power-law relation with the porosity as well as with pore or throat radius. Moreover, the relationship between intrinsic permeability and relative gas diffusivity can be expressed as k = 166.51(Dp/D0)0.98, which provides a direct means of estimating relative gas diffusion from intrinsic permeability directly.by Qiaoling Li, Jing Zhang, Shasha Meng, Fengxiang Tian, Qinqin Mei, Hui Wang, Hong Qi
BackgroundSelf-regulated fatigue is often assessed in studies of chronic diseases. Research is needed on the self-regulation of fatigue and physical activity in lung cancer patients undergoing treatment, and the impact of these factors on this population.
ObjectiveThe goal of this study is to investigate the current status, influencing factors, and correlation between self-regulatory fatigue and physical activity in lung cancer patients undergoing comprehensive treatment.
MethodsWe used a convenience sampling method to enroll 188 lung cancer patients admitted to two tertiary hospitals in Chengdu from October 2024 to April 2025. Data were collected using a general information questionnaire and two scales: the Self-Regulatory Fatigue Scale (SRF-S) and The International Physical Activity Questionnaire-long form (IPAQ-L).
ResultsThe mean self-regulatory fatigue score was 42.19 ± 9.06. The total metabolic equivalent (MET) of physical activity was 544.00 (0.00, 1386.00) MET-min/week, with leisure-time activity accounting for 429.00 (0.00, 1188.00) MET-min/week (data presented as median and interquartile range). Significant negative correlations were observed between Self-Regulatory Fatigue total scores and energy expenditure from housework, leisure activities, as well as total physical activity expenditure. Furthermore, self-regulatory fatigue was negatively correlated with both moderate-intensity and low-intensity physical activity, but positively correlated with high-intensity physical activity (P P R² = 0.306).
ConclusionEngaging in appropriate leisure and household activities at moderate-to-low intensity may help alleviate the severity of self-regulatory fatigue in lung cancer patients undergoing comprehensive treatment. Healthcare providers should encourage appropriate activity to reduce the psychological burden and conserve self-regulatory resources.
by Yuxuan Gao, Shiyao Jiang, Yu Cui, Yumeng Wang, Lili Yu
With the extensive clinical application of immune checkpoint inhibitors (ICIs), immune-related adverse events (irAEs) associated with these agents have increasingly garnered significant attention. Unlike other irAEs, endocrine irAEs are mostly irreversible, with variable and nonspecific symptoms, which poses challenges for clinicians in diagnosis. As a result, this study leveraged the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER) pharmacovigilance databases to conduct an in-depth investigation into adverse events induced by PD-1/PD-L1 inhibitors, with a focus on irAEs induced by PD-1/PD-L1 inhibitors. This study pioneers the systematic cross-database validation of endocrine irAEs induced by PD-1/PD-L1 inhibitors. The integration of data from the JADER offers unique safety insights for Asian populations, bolsters global pharmacovigilance efforts, and uncovers regional variations in irAEs reporting. Notably, this study revealed a higher prevalence of endocrine irAEs among men aged over 50 years receiving PD-1/PD-L1 inhibitors. Both PD-1 and PD-L1 inhibitors are strongly associated with thyroid dysfunction, adrenal insufficiency, and pituitary inflammation. Additionally, it identifies several previously undocumented endocrine irAEs. This result unearthed safety signals hitherto unreported in drug inserts, underscoring the imperative for updating the safety labeling of PD-1/PD-L1 inhibitors with respect to endocrine irAEs. The emergence of off-label uses further underscores the need for additional clinical trials to assess their efficacy and safety.by Thea Lynne Hedemann, Yun Lu, Sofia Campitelli, Lisa D. Hawke, Nelson Shen, Sarah Saperia, Brett D. M. Jones, Gillian Strudwick, Chelsey R. Wilks, Wei Wang, Marco Solmi, Michael Grossman, Muhammad Ishrat Husain, Nicole Kozloff, George Foussias, Muhammad Omair Husain
BackgroundYouth at clinical high risk (CHR) for psychosis often experience emotional dysregulation, psychiatric symptoms, substance use, suicidality, and functional impairment. Dialectical behaviour therapy (DBT) is an evidence-based intervention that improves emotion regulation, clinical outcomes, and functioning across psychiatric populations. Digital adaptations (d-DBT) may enhance accessibility and engagement for CHR youth, but acceptability and potential benefits in this group are unknown.
ObjectiveTo adapt d-DBT for CHR youth and evaluate the acceptability of delivering it to this population, as well as the feasibility of a larger-scale clinical trial.
MethodsThis mixed-methods clinical trial has two phases. In Phase 1, d-DBT will be adapted for CHR youth in collaboration with a lived-experience youth advisory group. In Phase 2, an assessor-masked randomized controlled trial will compare d-DBT (n = 30) with treatment as usual (n = 30). The intervention consists of eight weekly modules, with primary outcomes assessing acceptability, usability, and trial feasibility. Secondary outcomes include changes in emotional dysregulation, psychiatric symptoms, substance use, suicidality, and functioning.
ConclusionsWe anticipate that d-DBT will be acceptable to CHR youth and that conducting a larger trial will be feasible. Preliminary findings may demonstrate improvements in emotion regulation, psychiatric symptoms, suicidality, and functioning. Results will guide further refinement of the intervention and inform the design of a confirmatory clinical trial.
Trial registrationClinicalTrials.gov #NCT06928935
by Yun-Jin Hwang, So-Young Park, Jung-Hyun Park, Du-Hyong Cho
Vascular smooth muscle cells (VSMCs) plays an important role in maintaining vascular function by responding to various vasoactive stimuli within blood vessels. Far-infrared (FIR) rays has been shown to possess a variety of physiological effects including vasodilation, while the underlying molecular mechanism remains elusive. Here, we explored the molecular mechanism by which FIR irradiation suppresses vascular contraction using rat VSMCs and aortas. FIR irradiation enhanced the transport of intracellular Ca2+ from the cytosol to the sarcoendoplasmic reticulum (SER) via activation of sarcoendoplasmic reticulum Ca2+-ATPase (SERCA), which accompanied a decrease in intracellular ATP levels. Pretreatment with thapsigargin (TG), a specific SERCA inhibitor, or knockdown of SERCA2 gene expression reversed FIR irradiation-induced translocation of Ca2+ into the SER. Notably, FIR irradiation promoted the dissociation of SERCA2 and phospholamban (PLN), an endogenous SERCA inhibitor, without altering their total protein expression levels. The array of effects elicited by FIR irradiation was not observed under hyperthermic conditions (39°C). Moreover, FIR irradiation, but not hyperthermal condition, decreased the phosphorylation of myosin light chain (MLC) at Ser19, which was restored by pretreatment with TG or the knockdown of SERCA2 gene expression. FIR irradiation attenuated phenylephrine-induced vessel contraction in endothelium-deprived rat aortas. Consistent with the in vitro results, the reduction in MLC phosphorylation caused by FIR irradiation was reversed following pretreatment with TG in isolated aortas. Additionally, FIR irradiation increased blood flow in the carotid arteries of mice. Collectively, these results suggest that FIR irradiation activates SERCA2 by promoting its dissociation from PLN, independent of hyperthermic effects. This activation lowers cytosolic Ca²⁺ and ATP levels, reducing MLC phosphorylation and vascular smooth muscle contraction. These findings provide scientific evidence for the therapeutic potential of FIR therapy in the treatment and prevention of arterial narrowing conditions such as pathological vasospasm, and peripheral artery disease.by Bing-Nan Zhao, Zi-Yang Xie, Jia-Ning Liu, Xiao-Ran Chen, Xin-Xin Wang, Jia-Yi Li, Rui Zhang, Chao Si
Fermented spent coffee grounds (FSCG) serve as a valuable soil amendment to improve soil structure and fertility, while earthworms play a well-established role in enhancing soil processes and plant growth. However, their combined effects on bioactive compound accumulation in medicinal plants remain unclear. This study investigated the individual and interactive effects of FSCG (0%, 10%, and 20%, v/v) and earthworms (with and without Pheretima guillelmi) on the growth and phytochemical content of Glechoma longituba, a common medicinal herb, under greenhouse conditions. Results showed that 10% FSCG generally promoted plant growth, whereas 20% FSCG generally enhanced the accumulation of total flavonoids, chlorogenic acid, and soluble protein. Earthworms enhanced aboveground biomass and node number but significantly reduced chlorogenic acid content. These findings highlight the potential of FSCG as a sustainable soil amendment in medicinal plant cultivation and underscore the need to consider earthworm activity when optimizing both plant biomass and phytochemical quality.by Mi Lv, Hui Che, Jiayan Hu, Wenxi Yu, Zhaoxia Liu, Xiaolin Zhou, Binduo Zhou, Jinyi Xie, Fengyun Wang
BackgroundThe overlap between non-erosive reflux disease (NERD) and epigastric pain syndrome (EPS, a subtype of functional dyspepsia) is common, yet its associated factors remain poorly defined. We aimed to identify factors associated with symptom severity in NERD-EPS overlap, focusing on psychosocial and somatic factors.
MethodsIn this multicenter cross-sectional study, 800 patients meeting Rome IV criteria for NERD-EPS overlap were enrolled. Standardized questionnaires assessed gastrointestinal symptoms (GSRS), somatic symptoms (PHQ-15), anxiety/depression (PHQ-4), and sleep quality (SRSS). Multivariable regression models identified factors independently associated with GSRS scores, adjusted for demographics and clinical covariates. Interaction terms were tested to assess whether the association between one factor and GSRS scores varied across different levels of another factor.
ResultsOf the 800 patients, 67% were female, and the mean age was (44.50 ± 14.43) years. 67% had mild or more sleep problems, and 47% had anxiety or depression. Somatic symptoms (PHQ-15) showed the strongest association with GSRS scores (β = 0.617, P P P = 0.026). Urban residence (β = 0.071) and mixed labor type (β = −0.066) were also independently associated with symptom burden.
ConclusionSomatic symptoms, psychological distress, and sleep disturbances were the factors most strongly associated with symptom severity in NERD-EPS overlap, with additional contributions from younger age, male sex, and urban residence. Our findings advocate for integrated biopsychosocial interventions to alleviate symptom burden in this population.
by Yinli Shi, Shuang Guan, Sicun Wang, Muzhi Li, Yanan Yu, Jun Liu, Weibin Yang, Zhong Wang
BackgroundAlthough filgotinib, a selective Janus kinase 1 inhibitor, has been increasingly applied in the treatment of inflammatory diseases, its comprehensive safety profile remains insufficiently characterized. Using data from the FAERS database covering Q1 2014 to Q2 2024, this study attempts to analyze adverse event signals linked to filgotinib and provide guidance for the safe and sensible clinical usage of filgotinib.
MethodsFrom Q1 2014 to Q2 2024, information on adverse drug events (ADEs) associated with filgotinib was gathered. The reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) were among the signal detection methods that were employed for analysis following data normalization.
ResultsFilgotinib was shown to be the main suspected medication in ADE reports, exposing 103 preferred terms (PTs) in 17 system organ classes (SOCs). Infections, gastrointestinal disorders, and musculoskeletal and connective tissue disorders were the most commonly reported adverse effects. Additionally, atrial fibrillation, alopecia, elevated serum creatinine, blood creatinine increased, pulmonary embolism, epididymitis, respiratory failure, and osteopenia were identified as potential disproportionate reporting signals for filgotinib, although these were not listed in the official drug label. Notable significant signals included large intestine erosion (ROR 2186.05, 95%CI(ROR): 1015.94–4703.86, PRR 2176.18, 95%CI(PRR): 1014.64–4667.42), mesenteric arterial occlusion (ROR 1832.17, 95%CI(ROR): 897.68–3739.48, PRR 1822.71, 95%CI(PRR): 896.17–3707.20), repetitive strain injury (ROR 1149.27, 95%CI(ROR): 363.16–3637.01, PRR 1147.05, 95%CI(PRR): 363.24–3622.15), oligoarthritis (ROR 755.02, 95%CI(ROR): 310.74–1834.54, PRR 752.59, 95%CI(PRR): 310.60–1823.51), and periostitis (ROR 676.03, 95%CI(ROR): 319.36–1431.06, PRR 672.98, 95%CI(PRR): 318.97–1419.87). The subgroup analysis identified obvious sex and age-specific trends in filgotinib-related adverse reactions, emphasizing a higher risk of renal disorders in females, a preponderance of gastrointestinal events in males, and age-dependent trends involving mesenteric occlusion, increased serum creatinine, and immunoglobulin reduction.
ConclusionWhile filgotinib demonstrates therapeutic efficacy, it is associated with a range of potential adverse events, underscoring the need for vigilant clinical monitoring. Particular attention should be given to gastrointestinal, cardiovascular, respiratory, and metabolic complications.
by Hailang Wei, Qingyun Wang
Janus kinase 3 (JAK3) is a hematopoietic-specific kinase implicated in cytokine signaling and immune dysregulation and has recently been associated with cancer progression. However, selective and potent JAK3 inhibitors remain underdeveloped. In this study, we established a machine learning (ML)-based pipeline to identify novel JAK3 inhibitors with anti-cancer potential. A curated ChEMBL dataset of JAK3 inhibitors was used to train multiple ML classifiers, with the Random Forest model achieving the highest performance (AUC = 0.80, F1-score = 0.92). This model was applied to virtually screen 25,084 ChEMBL compounds, yielding 400 high-confidence candidates (prediction score > 0.9). Docking analysis identified ten top binders (binding affinity ≤ –8.5 kcal/mol), of which three CHEMBL49087, CHEMBL4117527, and CHEMBL50064 exhibited optimal ADMET profiles. These compounds underwent 200 ns molecular dynamics simulations, showing low RMSD (0.10–0.20 nm), stable binding conformations, and preserved protein compactness. MM/GBSA calculations revealed that CHEMBL4117527 displayed the strongest binding free energy (–29.5 kcal/mol), surpassing even the co-crystallized ligand (–17.7 kcal/mol). Our integrative approach combining machine learning, docking, pharmacokinetics, molecular dynamics, and free energy analysis presents a robust computational strategy for JAK3 inhibitor discovery. These findings support CHEMBL4117527 as promising candidates for further experimental evaluation in cancer therapeutics.by Allison Anbari, Zachary Massey, Abigail Adediran, Na Wang, LaRissa Lawrie, Priscilla Martinez, Denis McCarthy
Alcohol consumption increases breast cancer risk. We evaluated the responses of 748 United States female participants ages 21–29 to health warning messages addressing the relationship between alcohol consumption and increased breast cancer risk. In an online experiment, participants were randomly assigned to view standalone health warning messages about alcohol, breast cancer, and breast cancer health effects with varying picture and text attributes. Participants then completed post-message exposure assessments that included an immediate open-ended response to the message prompt. We conducted a qualitative content analysis of the responses and coded deductively based on constructs from the Message Impact Framework including message reactions, attitudes and beliefs, and behavioral intentions. These constructs and corresponding variables were present in participants’ responses. Response type did not vary by participants’ demographics or the attributes of the health warning message they viewed. The code new information was applied to 20% of the responses, indicating that those participants had no prior knowledge of alcohol and breast cancer risk. Alcohol and breast cancer messaging could impact drinking behaviors. Given the frequency of responses indicating a lack of awareness, more work in cancer prevention and population health messaging is warranted.by Qijun Wo, Jiafeng Shou, Jun Shi, Lei Shi, YunKai Yang, Yifan Wang, Liping Xie
Prostate cancer (PCa) remains a leading cause of cancer-related mortality in men, with challenges in diagnosis and treatment due to tumor heterogeneity. This study identifies palmitoylation-related signature genes as potential diagnostic and therapeutic targets. Integrating GEO datasets, six differentially expressed genes (DEGs) linked to palmitoylation were identified. Machine learning algorithms (LASSO, RF, SVM) selected three core genes: TRPM4, LAMB3, and APOE. A diagnostic model based on these genes achieved an AUC of 0.929, demonstrating robust accuracy in distinguishing PCa from normal tissues. Functional analysis revealed roles in lipid metabolism and immune modulation, with ssGSEA highlighting correlations between key genes and immune cell infiltration. Experimental validation showed that LAMB3 overexpression suppressed PCa cell proliferation, migration, and invasion, while knockdown enhanced these processes. Molecular docking identified diethylstilbestrol as a potential therapeutic agent targeting LAMB3 and APOE. These findings emphasize the clinical relevance of palmitoylation-related genes in PCa diagnosis and therapy, offering novel biomarkers and insights for personalized treatment strategies.by Jin-Hwa Kim, Ji-Soo Jeong, Jeong-Won Kim, Eun-Hye Chung, Su-Ha Lee, Je-Won Ko, Youn-Hwan Hwang, Tae-Won Kim
Moutan Cortex (MC), the dried root bark of Paeonia suffruticosa, is used in traditional Chinese and Korean medicine to treat enteritis for its anti-inflammatory properties. This study compared the pharmacokinetic (PK) profiles of paeonol and paeoniflorin in normal and dinitrobenzene sulfonic acid (DNBS)-induced colitis rats, and to determine how repeated low-dose MC [MC(L), 0.5 g/kg] or high-dose MC [MC(H), 2.5 g/kg] alters PK and disease severity. Using ultra-performance liquid chromatography–tandem mass spectrometry, we found that DNBS modestly increased paeonol AUClast (NC: 247.8 ± 63.7 vs DNBS: 337.0 ± 120.8 hr*ng/mL) and decreased paeoniflorin (NC: 474.1 ± 11.7 vs DNBS: 463.7 ± 106.8 hr*ng/mL) compared to controls (ns). After repeated dosing, the maximum plasma concentration (Cmax) of paeonol was higher in the MC(H) than that in the MC(L) group (MC(L): 63.81 ± 29.74 vs MC(H): 4221.5 ± 1579.2 ng/mL, p max in the MC(H) group was also higher than MC(L) group (MC(L): 60.5 ± 15.3 vs MC(H): 164.7 ± 74.7 ng/mL, pby Yizhuo Gong, Xinmeng Wang, Mingkun Yu, Peipei Zu
PurposeTo precisely evaluate the independent influence of two different optical zone (OZ) sizes (6.3 mm vs. 6.5 mm) on corneal biomechanical properties within 6 months after Small Incision Lenticule Extraction (SMILE) using multivariable-adjusted statistical models.
MethodsThis retrospective study included myopic patients who underwent SMILE between 2022 and 2024. Patients were grouped into two groups based on the planned OZ: Group A (6.3 mm, 44 eyes) and Group B (6.5 mm, 54 eyes). Corneal biomechanical parameters were measured using the Corvis ST preoperatively and at 1, 3, and 6 months postoperatively. Linear Mixed Models (LMM) were used to assess the independent effect of OZ size, adjusting for key baseline covariates and accounting for inter-eye correlation by including a random intercept for patient identifier (ID).
ResultsA total of 98 eyes were analyzed. Baseline analysis revealed a significant imbalance between the groups, with Group A (6.3 mm OZ) having higher myopia and a greater corneal stromal ablation depth (both P 0.05), with the sole exception of Ambrosio Relational Thickness Horizontal (ARTH) (P = 0.012). In contrast, several preoperative covariates, particularly corneal stromal ablation depth and preoperative central corneal thickness, were identified as significant predictors of multiple postoperative biomechanical parameters.
ConclusionThe independent effect of a 0.2 mm difference in optical zone size on corneal biomechanical properties after SMILE appears to be limited. After comprehensive statistical adjustment, the results suggest that preoperative anatomical and surgical parameters, especially corneal stromal ablation depth, are the primary drivers of the postoperative biomechanical response, rather than the minor difference in OZ size itself. This study underscores the importance of confounder adjustment in refractive surgery research and suggests that maximizing the residual stromal bed may be more critical for maintaining corneal biomechanical integrity than fine-tuning the optical zone diameter.
by Ju Liang, Fan Wang, Jia Chen, Hai-Yan Huang, Zu-Fan Dou
In UAV aerial photography scenarios, targets exhibit characteristics such as multi-scale distribution, a high proportion of small targets, complex occlusions, and strong background interference. These characteristics impose high demands on detection algorithms in terms of fine-grained feature extraction, cross-scale fusion capability, and occlusion resistance.The YOLOv11s model has significant limitations in practical applications: its feature extraction module has a single semantic representation, the traditional feature pyramid network has limited capability to detect multi-scale targets, and it lacks an effective feature compensation mechanism when targets are occluded.To address these issues, we propose a UAV aerial small target detection algorithm named UAS-YOLO (Universal Inverted Bottleneck with Adaptive BiFPN and Separated and Enhancement Attention module YOLO), which incorporates three key optimizations. First, an Adaptive Bidirectional Feature Pyramid Network (ABiFPN) is designed as the Neck structure. Through cross-scale connections and dynamic weighted fusion, ABiFPN adjusts weight allocation based on target scale characteristics, focusing on enhancing feature integration for scales related to small targets and improving multi-scale feature representation capability. Second, a Separated and Enhancement Attention Module (SEAM) is introduced to replace the original SPPF module. This module focuses on key target regions, enhances effective feature responses in unoccluded areas, and specifically compensates for information loss in occluded regions, thereby improving the detection stability of occluded small targets. Third, a Universal Inverted Bottleneck (UIB) structure is proposed, which is fused with the C3K2 module to form the C3K2_UIB module. By leveraging dynamic channel attention and spatial feature recalibration, C3K2_UIB suppresses background noise; although this increases parameters by 34%, it achieves improved detection accuracy through efficient feature selection, striking a balance between accuracy and complexity.Experimental results show that on the VisDrone2019 dataset and the TinyPerson dataset from Kaggle, the mean Average Precision (mAP) of the algorithm is increased by 4.9 and 2.1 percentage points, respectively. Moreover, it demonstrates greater advantages compared to existing advanced algorithms, effectively addressing the challenge of small target detection in complex UAV scenarios.
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