A single-cell 3D dynamic volume control system for chondrocytes.

In articular cartilage, zone-specific cellular morphology is a typical characteristic of cartilage tissue, which is related with chondrocyte function, inflammation and osteoarthritis (OA). Chondrocyte hypertrophic phenotype is a criticle physiological process which indicates a hallmark of chondrocyte terminal differentiation and bone formation. Thus, developing a in vitro cell culture system for dynamic regulation of single chondrocyte volume at a three-dimensional (3D) level is particularly necessary for understanding how physical cues of matrix microenvironment regulate chondrocyte fate and the degeneration of articular cartilage. Here, based on the soft lithography techniques, we have constructed well-defined single-cell 3D dynamic volume control system to recapitulate the physiological matrix microenvironment of single chondrocyte niche. The results of finite element analysis indicated that the stress and strain distribution in the cell culture region is homogeneous during the stretching process. Additionally, 3D dynamic volume expansion and compression of single cells in physiological or hyperphysiological can be realized in this cell culture system. Our device for single-cell 3D dynamic culture provides a microphysiological culture system for chondrocytes to explore the mechanisms of cartilage hypertrophy, as well as develops a new paradigm for functional cartilage tissue engineering and regenerative medicine.

SolidWorks software was used to design various components of 3D dynamic volume control system. Leveraging lithography microfabrication techniques, the polydimethylsiloxane (PDMS) 3D niches were fabricated with controlled geometry and volume on PDMS stretching substrate. Finite element analysis softwares (Abaqus and Comsol) were used to analyze the strain distribution of PDMS stretching substrate and single 3D niche. The elastic moduli of PDMS stretching substrate were measured using an Instron 5544. Furthermore, immunofluorescence staining was performed to assess the morphology and cytoskeletal reorganization of chondrocyte encapsulated in PDMS 3D niches. ImageJ software was used to quantitatively analyze immunofluorescence images.

Comprehensive analysis of cuproptosis-related genes involved in prognosis and tumor microenvironment infiltration of colorectal cancer.

Background: Colorectal cancer (CRC) is a common malignancy, with high incidence and high mortality rates. Cuproptosis, a novel form of copper-induced programmed cell death, contributes to tumor progression. However, whether cuproptosis-related genes (CRGs) play a role in CRC remains unclear. This study aims to elucidate the role of CRGs in CRC development, patient prognosis, and immune response. Methods: We performed bioinformatics analysis of the differential expression of CRGs between CRC and normal tissues. Least absolute shrinkage and selection operator (LASSO), and univariate and multivariate Cox analyses were employed to identify risk factors, which were used to construct a risk score model. Patients with CRC were categorized into high- and low-risk groups based on their median risk scores. Receiver operating characteristic curve analysis was used to verify the predictive accuracy of the risk model. A nomogram was developed for CRC through univariate and multivariate Cox regression analyses. The chemotherapeutic drug sensitivity was compared between patients with high and low CDKN2A/DLAT expression using the Wilcoxon rank-sum test. Spearman's correlation and TISIDB database analyses were conducted to determine relationships between CDKN2A or DLAT and immune cell infiltration. Results: Eight of ten identified CRGs exhibited significant differential expression between CRC and normal tissues. Among the eight significant differential expression CRGs, CDKN2A and DLAT were identified as independent risk factors for predicting overall survival (OS) in CRC. Patients with CRC in the low-risk group had longer OS than those in the high-risk group. The risk score model had good predictive accuracy for OS. Based on CDKN2A, DLAT and some clinical characteristics, a prognostic nomogram was developed to predict OS for CRC patients and showed good predictive ability. CDKN2A and DLAT expressions were significantly associated with chemotherapeutic drug sensitivity and immune cell infiltration in CRC, and the molecular subtypes and immune subtypes differed between CDKN2A and DLAT. Conclusions: Our research revealed the prognostic value of CRGs, particularly CDKN2A and DLAT, in CRC and demonstrated the relationship between CDKN2A/DLAT and immune infiltration in CRC, thereby contributing to the outcome evaluation of patients with CRC and identifying novel targets for CRC immunotherapy.

Permeation characteristics and cross-linking efficacy of iontophoresis-assisted riboflavin delivery for accelerated riboflavin-ultraviolet A scleral collagen cross-linking in porcine eyes.

The purpose of this study is to investigate whether the iontophoresis-assisted riboflavin delivery to posterior sclera with less delivery time, can achieve the same riboflavin permeation efficiency as the passive soaking way, and its effect on the mechanical properties of posterior sclera for accelerated scleral collagen cross-linking (A-SXL). In this study, 0.1% riboflavin solution was applied into the posterior sclera of porcine eyes either by the iontophoresis-assisted or passive soaking method, with delivery time of 5, 7.5, 10, 12.5, 15, 17.5, and 20 min, respectively. The fluorescence intensity and the distribution of riboflavin concentration in the 10 µm frozen sections of the sclera were evaluated by fluorescence inverted microscope. The posterior sclera with riboflavin treatment through either the iontophoresis-assisted or the passive soaking method for different durations ranging from 5 to 20 min was treated with ultraviolet A (UVA) irradiation at an intensity of 10 mW/cm2 for 9 min. The elastic modulus was determined at the physiological strain level using the uniaxial tensile test after ASXL. The results showed that the fluorescence intensity of riboflavin increased by prolonging the delivery time in both the iontophoresis and passive soaking groups, and the permeation depth of riboflavin remained constant over 15 min. The fluorescence intensity in the iontophoresis group was significantly higher than in the passive soaking group at 12.5 min and 15 min, respectively. The elastic modulus at 12.5 min in the iontophoresis group was significantly higher than in the passive soaking group at the same delivery time and showed no significant difference compared to the passive soaking group at 20 min. In conclusion, it indicated that iontophoresis-assisted delivery could not only shorten the surgery time but also achieve similar mechanical performance to the passive soaking method in ASXL.

Fabrication and in vitro biocompatibility of hierarchical cellulose acetate/polyvinylpyrrolidone@titania nanowire hollow microfibers.

In this study, hierarchical cellulose acetate/polyvinylpyrrolidone hollow microfibers (CA/PVP HMFs) were first prepared via a dip coating method using a steel wire as tubular template and then supported a sol-gel deposition of titania nanoparticles (NPs) to derive CA/PVP@titania NP HMFs. After hydrothermally treated in NaOH solution, CA/PVP@titania NP HMFs were transformed to CA/PVP@titania nanowire (NW) HMFs. SEM observation showed that CA/PVP@titania NW HMFs had a hollow structure with diameters of 450-600 µm and exhibited a hierarchical and nanofibrous structure. Their surfaces were constructed by numerous titania NWs with diameters of 10-30 nm and lengths of 1-5 µm. The incorporation of PVP not only caused a significant change in surface wettability from hydrophobic CA HMFs to hydrophilic CA/PVP HMFs, but also promoted the sol-gel deposition of titania NPs on CA/PVP HMFs. CA/PVP@titania NW HMFs exhibited the highest hydrophilicity with water contact angle of 32° and the largest specific surface area of 86.1 m2/g. In vitro biocompatible evaluation indicated that CA/PVP@titania NW HMFs exhibited much higher cell adhesion and proliferation than CA/PVP@titania NP HMFs and CA/PVP HMFs within 7 days due to the presence of nanofibrous surface architecture. Thus, the present CA/PVP titania NW HMFs have potential as biocompatible cell supporting matrices.

Treatment response of venlafaxine induced alterations of gut microbiota and metabolites in a mouse model of depression.

Antidepressants remain the first-line treatment for depression. However, the factors influencing medication response are still unclear. Accumulating evidence implicates an association between alterations in gut microbiota and antidepressant response. Therefore, the aim of this study is to investigate the role of the gut microbiota-brain axis in the treatment response of venlafaxine. After chronic social defeat stress and venlafaxine treatment, mice were divided into responders and non-responders groups. We compared the composition of gut microbiota using 16 S ribosomal RNA sequencing. Meanwhile, we quantified metabolomic alterations in serum and hippocampus, as well as hippocampal neurotransmitter levels using liquid chromatography-mass spectrometry. We found that the abundances of 29 amplicon sequence variants (ASVs) were significantly altered between the responders and non-responders groups. These ASVs belonged to 8 different families, particularly Muribaculaceae. Additionally, we identified 38 and 39 differential metabolites in serum and hippocampus between the responders and non-responders groups, respectively. Lipid, amino acid, and purine metabolisms were enriched in both serum and hippocampus. In hippocampus, the concentrations of tryptophan, phenylalanine, gamma-aminobutyric acid, glutamic acid, and glutamine were increased, while the level of succinic acid was decreased in the responders group, compared with the non-responders group. Our findings suggest that the gut microbiota may play a role in the antidepressant effect of venlafaxine by modulating metabolic processes in the central and peripheral tissues. This provides a novel microbial and metabolic framework for understanding the impact of the gut microbiota-brain axis on antidepressant response.

Feature Extraction Methods for Underwater Acoustic Target Recognition of Divers.

The extraction of typical features of underwater target signals and excellent recognition algorithms are the keys to achieving underwater acoustic target recognition of divers. This paper proposes a feature extraction method for diver signals: frequency-domain multi-sub-band energy (FMSE), aiming to achieve accurate recognition of diver underwater acoustic targets by passive sonar. The impact of the presence or absence of targets, different numbers of targets, different signal-to-noise ratios, and different detection distances on this method was studied based on experimental data under different conditions, such as water pools and lakes. It was found that the FMSE method has the best robustness and performance compared with two other signal feature extraction methods: mel frequency cepstral coefficient filtering and gammatone frequency cepstral coefficient filtering. Combined with the commonly used recognition algorithm of support vector machines, the FMSE method can achieve a comprehensive recognition accuracy of over 94% for frogman underwater acoustic targets. This indicates that the FMSE method is suitable for underwater acoustic recognition of diver targets.

Associations of dietary patterns with risk of gastrointestinal disorders: a prospective cohort study.

Gastrointestinal (GI) disorders are highly prevalent and severely diminish life quality. It is yet unknown which dietary pattern is optimal for the prevention of GI disorders. Among 141 450 participants from UK Biobank with a median follow-up of 15 years, we comprehensively assessed 13 dietary patterns in relation to 6 GI disorders. Multivariable Cox proportional hazards models demonstrated that adherence to healthy diets was associated with lower risk of GI disorders, with the strongest associations observed for the Dietary Approaches to Stop Hypertension (DASH) diet (HRQ4 vs. Q1 = 0.85, 95% CI: 0.81, 0.88), the Alternate Mediterranean Diet (AMED) (HRQ4 vs. Q1 = 0.85, 95% CI: 0.81, 0.88), and the Alternate Healthy Eating Index-2010 (AHEI-2010) (HRQ4 vs. Q1 = 0.86, 95% CI: 0.82, 0.89). AHEI-2010 (HRs ranging from 0.76 to 0.90) and DASH (HRs ranging from 0.75 to 0.88) showed inverse associations with every individual GI disorder. Furthermore, comorbidities decreased significantly in number with higher AMED and DASH diet scores (P for trend <0.001). Finally, the associations of AHEI-2010, AMED and DASH with GI disorders diminished most intensely after removing the component of fruits or whole grains. The combined intake of fruits and whole grains was inversely associated with the risk of overall GI disorders (HRT3 vs. T1 = 0.89, 95% CI: 0.86, 0.93). In conclusion, AHEI-2010 and DASH were the most recommended dietary patterns for the prevention of GI disorders. Fruits and whole grains are the most significant contributors to the protective effect.

Disulfiram inhibits coronaviral main protease by conjugating to its substrate entry site.

Coronaviruses (CoV) are highly pathogenic single-strand RNA viruses. CoV infections cause fatal respiratory symptoms and lung injuries in humans and significant economic losses in livestock. Since the SARS-2 outbreak in 2019, the highly conserved main protease (Mpro), also termed 3-chymotrypsin-like protease (3CLpro), has been considered an attractive drug target for treating CoV infections. Mpro mediates the proteolytic cleavage of eleven sites in viral polypeptides necessary for virus replication. Here, we report that disulfiram, an FDA-approved drug for alcoholic treatment, exhibits a broad-spectrum inhibitory effect on CoV Mpros. Analytical ultracentrifugation and circular dichroism analyses indicated that disulfiram treatment blocks the dimeric formation of SARS and PEDV Mpros and decreases the thermostability of SARS, SARS-2, and PEDV Mpros, whereas it facilitates the dimerization and stability of MERS Mpro. Furthermore, mass spectrometry and structural alignment revealed that disulfiram targets the Cys44 residue of Mpros, which is located at the substrate entrance and close to the catalytic His41. In addition, molecular docking analysis suggests that disulfiram conjugation interferes with substrate entry to the catalytic center. In agreement, mutation of Cys44 modulates the disulfiram sensitivity of CoV Mpros. Our study suggests a broad-spectrum inhibitory function of disulfiram against CoV Mpros.

Associations of ultraprocessed food consumption with mortality among participants with a history of cancer: a prospective cohort analysis.

BACKGROUND: Although high ultraprocessed food (UPF) consumption has been linked with increased mortality risk in the general population, whether UPFs harm participants with a history of cancer remains unclear. OBJECTIVES: This study aimed to evaluate the association of UPF consumption with mortality among participants with a history of cancer. METHODS: Prospective cohort analysis was conducted on 13,640 participants with a history of cancer from the UK Biobank. UPFs were defined by the Nova classification. UPF consumption was calculated as the weight proportion of UPFs in the total food consumption. Cox proportional hazard models were used to assess the association between UPF consumption and mortality among participants with a history of cancer. RESULTS: The median UPF consumption was 29.25% (interquartile range [IQR]: 19.46%-40.62%) for males and 25.81% (IQR: 16.61%-36.35%) for females in the total diet among participants with a history of cancer. During a median follow-up of 10.77 years, 1611 deaths were documented. Multivariable-adjusted hazard ratios (95% confidence intervals) among participants in the highest quartile of UPF consumption relative to the lowest were 1.17 (1.02, 1.35) for all-cause mortality and 1.22 (1.03, 1.44) for cancer-related mortality. CONCLUSIONS: Higher UPF consumption after the diagnosis among participants with a history of cancer is associated with higher risk of mortality.

[Study on methods measuring mechanical properties of arterial wall by macroscopic indentation].

Accurately evaluating the local biomechanics of arterial wall is crucial for diagnosing and treating arterial diseases. Indentation measurement can be used to evaluate the local mechanical properties of the artery. However, the effects of the indenter's geometric structure and the analysis theory on measurement results remain uncertain. In this paper, four kinds of indenters were used to measure the pulmonary aorta, the proximal thoracic aorta and the distal thoracic aorta in pigs, and the arterial elastic modulus was calculated by Sneddon and Sirghi theory to explore the influence of the indenter geometry and analysis theory on the measured elastic modulus. The results showed that the arterial elastic modulus measured by cylindrical indenter was lower than that measured by spherical indenter. In addition, compared with the calculated results of Sirghi theory, the Sneddon theory, which does not take adhesion forces in account, resulted in slightly larger elastic modulus values. In conclusion, this study provides parametric support for effective measurement of arterial local mechanical properties by millimeter indentation technique.

Electrochromic visualization of latent fingermarks deposited on nonconductive surfaces.

Electrochromic visualization of latent fingermarks has already been achieved on conducting surfaces such as stainless steel. However, their enhancement on non-conducting surfaces such as glass via electrochromism has not been reported. Considering the non-conductive nature of substrates, a layer of gold was introduced to the fingermark-bearing surfaces, in which gold was used as the cathodes to assemble electrochromic devices for visualization. The contact between gold nanoparticles of the as-obtained conducting layer in the fingermark region should be affected by the height difference within the fingermark, leading to conductivity differences, which give rise to coloration differences in electrochromic devices. It is demonstrated that 1,1'-dibenzyl-4,4'-bipyridinium dichloride can be used as the electrochromic chromophore for the visualization of latent fingermarks deposited on nonconducting surfaces, and the primary and secondary characteristic information can be obtained. The electrochromic visualization herein solves the problem of electrochromically enhancing latent fingermarks on non-conducting surfaces.

Engineered Probiotic Bio-Heterojunction with Robust Antibiofilm Modality via "Eating" Extracellular Polymeric Substances for Wound Regeneration.

The compact three-dimensional (3D) structure of extracellular polymeric substances (EPS) within biofilms significantly hinders the penetration of antimicrobial agents, making biofilm eradication challenging and resulting in persistent biofilm-associated infections. To address this challenge, a solution is proposed: a probiotic bio-heterojunction (P-bioHJ) combining Lactobacillus rhamnosus with MXene (Ti3C2) quantum dots (MQDs)/FeS heterojunction. This innovation aims to break down the saccharides in EPS, enabling effective combat against biofilm-associated infections. Initially, the P-bioHJ targets saccharides through metabolic processes, causing the collapse of EPS and allowing infiltration into bacterial colonies. Simultaneously, upon exposure to near-infrared (NIR) irradiation, the P-bioHJ produces reactive oxygen species (ROS) and thermal energy, deploying physical mechanisms to combat bacterial biofilms effectively. Following antibiofilm treatment, the P-bioHJ adjusts the oxidative environment, reduces wound inflammation by scavenging ROS, boosts antioxidant enzyme activity, and mitigates the NF-κB inflammatory pathway, thereby accelerating wound healing. In vitro and in vivo experiments confirm the exceptional antibiofilm, antioxidant/anti-inflammatory, and wound-regeneration properties of P-bioHJ. In conclusion, this study provides a promising approach for treating biofilm-related infections.

Mesencephalic Astrocyte-derived Neurotrophic Factor Supports Hepatitis B Virus-induced Immunotolerance.

BACKGROUND & AIMS: The immune tolerance induced by hepatitis B virus (HBV) is a major challenge for achieving effective viral clearance, and the mechanisms involved are not well-understood. One potential factor involved in modulating immune responses is mesencephalic astrocyte-derived neurotrophic factor (MANF), which has been reported to be increased in patients with chronic hepatitis B. In this study, our objective is to examine the role of MANF in regulating immune responses to HBV. METHODS: We utilized a commonly used HBV-harboring mouse model, where mice were hydrodynamically injected with the pAAV/HBV1.2 plasmid. We assessed the HBV load by measuring the levels of various markers including hepatitis B surface antigen, hepatitis B envelope antigen, hepatitis B core antigen, HBV DNA, and HBV RNA. RESULTS: Our study revealed that following HBV infection, both myeloid cells and hepatocytes exhibited increased expression of MANF. Moreover, we observed that mice with myeloid-specific MANF knockout (ManfMye-/-) displayed reduced HBV load and improved HBV-specific T cell responses. The decreased HBV-induced tolerance in ManfMye-/- mice was associated with reduced accumulation of myeloid-derived suppressor cells (MDSCs) in the liver. Restoring MDSC levels in ManfMye-/- mice through MDSC adoptive transfer reinstated HBV-induced tolerance. Mechanistically, we found that MANF promoted MDSC expansion by activating the IL-6/STAT3 pathway. Importantly, our study demonstrated the effectiveness of a combination therapy involving an hepatitis B surface antigen vaccine and nanoparticle-encapsulated MANF siRNA in effectively clearing HBV in HBV-carrier mice. CONCLUSION: The current study reveals that MANF plays a previously unrecognized regulatory role in liver tolerance by expanding MDSCs in the liver through IL-6/STAT3 signaling, leading to MDSC-mediated CD8+ T cell exhaustion.

Identification of Potential Biomarkers for Major Depressive Disorder: Based on Integrated Bioinformatics and Clinical Validation.

Major depressive disorder (MDD) is a severe mental illness characterized by a lack of objective biomarkers. Mounting evidence suggests there are extensive transcriptional molecular changes in the prefrontal cortex (PFC) of individuals with MDD. However, it remains unclear whether there are specific genes that are consistently altered and possess diagnostic power. In this study, we conducted a systematic search of PFC datasets of MDD patients from the Gene Expression Omnibus database. We calculated the differential expression of genes (DEGs) and identified robust DEGs using the RRA and MetaDE methods. Furthermore, we validated the consistently altered genes and assessed their diagnostic power through enzyme-linked immunosorbent assay experiments in our clinical blood cohort. Additionally, we evaluated the diagnostic power of hub DEGs in independent public blood datasets. We obtained eight PFC datasets, comprising 158 MDD patients and 263 healthy controls, and identified a total of 1468 unique DEGs. Through integrated analysis, we identified 290 robustly altered DEGs. Among these, seven hub DEGs (SLC1A3, PON2, AQP1, EFEMP1, GJA1, CENPD, HSD11B1) were significantly down-regulated at the protein level in our clinical blood cohort. Moreover, these hub DEGs exhibited a negative correlation with the Hamilton Depression Scale score (P < 0.05). Furthermore, these hub DEGs formed a panel with promising diagnostic power in three independent public blood datasets (average AUCs of 0.85) and our clinical blood cohort (AUC of 0.92). The biomarker panel composed of these genes demonstrated promising diagnostic efficacy for MDD and serves as a useful tool for its diagnosis.

Diallyl trisulfide induces pyroptosis and impairs lung CSC-like properties by activating the ROS/Caspase 1 signaling pathway.

Lung cancer stem cells (CSCs) drive continuous cancer growth and metastatic dissemination; thus, there is an urgent requirement to acquire effective therapeutic strategies for targeting lung CSCs. Diallyl trisulfide (DATS), a garlic organosulfide, possesses suppressive potential in lung cancer; however, its underlying mechanism is still unclear. In this study, we identified DATS as a pyroptosis inducer in lung cancer cells. DATS-treated A549 and H460 cells exhibited pyroptotic cell death, with characteristic large bubbles appearing on their plasma membrane and LDH release. DATS induced cell death, arrested the cell cycle at the G2/M phase, and inhibited colony formation in lung cancer cells. Meanwhile, we found that DATS significantly suppressed the malignant features by impairing lung CSC-like properties, including sphere formation ability, CD133 positive cell number, and lung CSCs marker expression. Mechanistically, DATS induced cell pyroptosis via increasing the expression of NLRP3, ASC, Pro Caspase 1, Cleaved Caspase 1, GSDMD, GSDMD-N, and IL-1ß. The verification experiments showed that the effects of DATS on pyroptosis and lung CSC-like properties were weakened after Caspase 1 inhibitor VX-765 treatment, indicating that DATS activated NLRP3 inflammasome-mediated pyroptosis by targeting Caspase 1 in lung cancer cells. Moreover, DATS increased ROS overproduction and mitochondrial dysfunction, which contributed to DATS-induced pyroptosis of lung cancer cells. NAC treatment reversed the effects of DATS on pyroptosis and CSC-like properties. In vivo experiment further confirmed that DATS restrained tumor growth. Together, our results suggest that DATS promotes pyroptosis and impairs lung CSC-like properties by activating ROS/Caspase 1 signaling pathway, thereby retarding lung cancer progression.

ProMENDA: an updated resource for proteomic and metabolomic characterization in depression.

Depression is a prevalent mental disorder with a complex biological mechanism. Following the rapid development of systems biology technology, a growing number of studies have applied proteomics and metabolomics to explore the molecular profiles of depression. However, a standardized resource facilitating the identification and annotation of the available knowledge from these scattered studies associated with depression is currently lacking. This study presents ProMENDA, an upgraded resource that provides a platform for manual annotation of candidate proteins and metabolites linked to depression. Following the establishment of the protein dataset and the update of the metabolite dataset, the ProMENDA database was developed as a major extension of its initial release. A multi-faceted annotation scheme was employed to provide comprehensive knowledge of the molecules and studies. A new web interface was also developed to improve the user experience. The ProMENDA database now contains 43,366 molecular entries, comprising 20,847 protein entries and 22,519 metabolite entries, which were manually curated from 1370 human, rat, mouse, and non-human primate studies. This represents a significant increase (more than 7-fold) in molecular entries compared to the initial release. To demonstrate the usage of ProMENDA, a case study identifying consistently reported proteins and metabolites in the brains of animal models of depression was presented. Overall, ProMENDA is a comprehensive resource that offers a panoramic view of proteomic and metabolomic knowledge in depression. ProMENDA is freely available at https://menda.cqmu.edu.cn .

Genotoxicity and cytotoxicity in male reproductive cells caused by sediment pollutants.

In recent years, mounting evidence has highlighted a global decline in male semen quality, paralleling an increase in male infertility problems. Such developments in the male reproductive system are likely due to a range of environmental factors, which could negatively affect the outcomes of pregnancy, reproductive health, and the well-being of fetuses. Different environmental contaminants ultimately accumulate in riverbed sediments due to gravity, so these sediments are frequently considered hotspots for pollutants. Therefore, understanding the detrimental effects of river sediment pollution on human reproductive health is crucial. This study indicates male germ cells' high vulnerability to environmental contaminants. There is a strong positive correlation between the concentration of complex accumulated pollutants from human activities and the reproductive toxicity observed in human testicular embryonic cell lines NCCIT and NTERA-2. This toxicity is characterized by increased levels of reactive oxygen species, disruption of critical cellular functions, genotoxic impacts, and the induction of cell apoptosis. This research marks a significant step in providing in vitro evidence of the damaging effects of environmental pollutants on the human male germline.

Post-diagnostic lifestyle and mortality of cancer survivors: Results from a prospective cohort study.

OBJECTIVE: Lifestyle factors after cancer diagnosis could influence cancer survival. This study aimed to investigate the joint effects of smoking, physical activity, alcohol consumption, diet and sleep duration on all-cause, cancer and non-cancer mortality of cancer survivors in UK biobank. METHODS: The follow-up period concluded in December 2021, with post-diagnostic lifestyle factors assessed at baseline. A lifestyle score ranging from 0 to 5 was assigned based on adherence to the selected lifestyle factors. The study employed Cox regression models for hazard ratios (HRs) and Kaplan-Meier for survival rates, with stratified and sensitivity analyses to assess the robustness of our findings under various assumptions. RESULTS: During a median follow-up of 12.7 years, 5652 deaths were documented from 34,184 cancer survivors. Compared to scoring 0-1, the HRs (95% CIs) for all-cause mortality with lifestyle scores of 2, 3, 4, and 5 were 0.70 (95% CI: 0.64, 0.76), 0.57 (0.52, 0.62), 0.50 (0.45, 0.54) and 0.43 (0.38, 0.48), respectively. Specific cancer types, particularly digestive, breast, female reproductive, non-solid, and skin cancers, showed notable benefits from adherence to healthy lifestyle, with the HRs of 0.55 (0.39, 0.79), 0.54 (0.42, 0.70), 0.32 (0.19, 0.53), 0.58 (0.39, 0.86), and 0.36 (0.28, 0.46) for lifestyle score of 5, respectively. Stratified analyses indicated the association was particularly significant among those with normal/lower BMI and higher Townsend Deprivation Index (Pinteraction = 0.001 and < 0.001, respectively). CONCLUSIONS: Healthier lifestyles were significantly linked with reduced mortality among cancer survivors. These findings highlight the need for adherence to healthy lifestyle habits to improve survival.

TAF2, within the TFIID complex, regulates the expression of a subset of protein-coding genes.

TFIID, one of the general transcription factor (GTF), regulates transcriptional initiation of protein-coding genes through direct binding to promoter elements and subsequent recruitment of other GTFs and RNA polymerase II. Although generally required for most protein-coding genes, accumulated studies have also demonstrated promoter-specific functions for several TFIID subunits in gene activation. Here, we report that TBP-associated factor 2 (TAF2) specifically regulates TFIID binding to a small subset of protein-coding genes and is essential for cell growth of multiple cancer lines. Co-immunoprecipitation assays revealed that TAF2 may be sub-stoichiometrically associated with the TFIID complex, thus indicating a minor fraction of TAF2-containing TFIID in cells. Consistently, integrated genome-wide profiles show that TAF2 binds to and regulates only a small subset of protein-coding genes. Furthermore, through the use of an inducible TAF2 degradation system, our results reveal a reduction of TBP/TFIID binding to several ribosomal genes upon selective ablation of TAF2. In addition, depletion of TAF2, as well as the TAF2-regulated ribosomal protein genes RPL30 and RPL39, decreases ribosome assembly and global protein translation. Collectively, this study suggests that TAF2 within the TFIID complex is of functional importance for TBP/TFIID binding to and expression of a small subset of protein-coding genes, thus establishing a previously unappreciated promoter-selective function for TAF2.