Immunoprotective efficacy evaluation of OmpTS subunit vaccine against Aeromonas hydrophila infection in Megalobrama amblycephala.

Bacterial septicemia in freshwater fish is mainly caused by Aeromonas hydrophila infection, which affects the development of aquaculture industry. In the context of sustainable aquaculture, subunit vaccines are of great values because they play positive roles in reducing the overuse of antibiotics and protecting aquatic animals against bacterial infection. In this study, the recombinant outer membrane protein OmpTS of A. hydrophila were used as subunit vaccine to immunize Megalobrama amblycephala, and its immunoprotective effect and host immune responses were evaluated. The survival rates of the vaccinated groups after bacterial infection were significantly higher than that of the control group, especially of the OmpTS high-dose vaccinated group. The better protective effects of vaccinated groups might be attributed to the increased levels of serum IgM-specific antibody titer, the reduced relative abundance of A. hydrophila in various tissues, the increased number of immune-positive cells with different epitopes, the up-regulated expression levels of immune-related genes, and the enhanced activities of antibacterial enzymes. In conclusion, OmpTS subunit vaccine could strongly induce host immune responses in M. amblycephala, thereby enhancing both cellular and humoral immunity, which exhibited excellent and effective immunoprotective efficacy.

Rapid detection of common variants and deletions of CYP21A2 using MALDI-TOF MS.

Newborn screening (NBS) for congenital adrenal hyperplasia (CAH) based on hormonal testing is successfully implemented in many countries. However, this method cannot detect non-classic CAH and has high false positive rates. We have developed a novel MALDI-TOF MS assay that can identify common variants and deletions of CYP21A2 in the Chinese population.Thirty-seven clinical patients with CAH confirmed by Sanger sequencing and MLPA analysis were detected by MALDI-TOF MS assay. Two CYP21A2 variants were detected in 30 patients and one CYP21A2 variant was detected in 7 patients. The MALDI-TOF MS assay detected 67 mutant alleles in 37 patients with a detection rate of 90.5%. Sanger sequencing revealed that three variants in seven patients were not included in the designed panel. Eleven distinct CYP21A2 variants were identified, including five missense variants, two nonsense variants, two large gene deletions, one splice variant, and one frameshift variant. The most frequent variant was c.293-13C>G (37.84%), followed by c.518T>A (21.62%) and exon 1-7 deletion (17.57%). The high-throughput MALDI-TOF MS assay that can simultaneously detect common variants and deletions of CYP21A2. This assay can be used for population-based genetic screening and rapid detection of suspected patients, and is expected to be a valuable complement to biochemical-based testing for the detection of CAH.

Trends in breast cancer mortality attributable to metabolic risks in Chinese women from 1990 to 2019: an age-period-cohort analysis.

Objective: Metabolic risks (MRs) are the primary determinants of breast cancer (BC) mortality among women. This study aimed to examine the changing trends in BC mortality associated with MRs and explore how they related to age, time period, and birth cohorts in Chinese women aged 25 and above. Methods: Data were sourced from the Global Burden of Disease Study 2019 (GBD2019). The BC mortality trajectories and patterns attributable to MRs were assessed using Joinpoint regression. The age-period-cohort (APC) model was employed to evaluate cohort and time period effects. Results: The age-standardized mortality rate (ASMR) of BC mortality linked to MRs displayed an escalating trend from 1990 to 2019, demonstrating an average annual percentage change (AAPC) of 1.79% (95% CI: 1.69~1.87). AAPCs attributable to high fasting plasma glucose (HFPG) and high body mass index (HBMI) were 0.41% (95% CI: 0.32~0.53) and 2.75% (95% CI: 2.68~2.82), respectively. APC analysis revealed that BC mortality due to HBMI in women aged 50 and above showed a rise with age and mortality associated with HFPG consistently demonstrated a positive correlation with age. The impact of HBMI on BC mortality significantly outweighed that of HFPG. The risk of BC mortality linked to HBMI has steadily increased since 2005, while HFPG demonstrated a trend of initial increase followed by a decrease in the period effect. Regarding the cohort effect, the relative risk of mortality was greater in the birth cohort of women after the 1960s of MRs on BC mortality, whereas those born after 1980 displayed a slight decline in the relative risk (RR) associated with BC mortality due to HBMI. Conclusion: This study suggests that middle-aged and elderly women should be considered as a priority population, and control of HBMI and HFPG should be used as a primary tool to control metabolic risk factors and effectively reduce BC mortality.

Interrelationships among abnormal P-wave axis, metabolic syndrome and its components, and mortality in US adults.

BACKGROUND: Metabolic syndrome (MetS) is associated with increased rates of cardiovascular disease and mortality and is linked to abnormal electrocardiogram (ECG) parameters. We aimed to explore the relationships and interactions among MetS and its components, abnormal P-wave axis (aPWA), and mortality rates. METHODS: We analyzed data from 7526 adult participants with sinus rhythm recruited from the National Health and Nutrition Examination Survey III. MetS was classified based on the NCEP ATP III-2005 definition. aPWA included all P-wave axis outside 0-75°. The National Death Index was utilized to identify survival status. Hazard ratios (HRs) and 95% confidence intervals (CIs) categorized by aPWA, MetS, and their components were analyzed using Cox proportional hazards models to investigate all-cause and cardiovascular mortalities. RESULTS: Within a median follow-up period of 20.76 years, 4686 deaths were recorded, of which 1414 were attributable to cardiovascular disease. Participants with both MetS and aPWA had higher all-cause (HR: 1.45, 95% CI: 1.29-1.64, interaction P = 0.043) and cardiovascular (HR: 1.36, 95% CI: 1.02-1.79, interaction P-value = 0.058) mortality rates than participants without MetS and with a normal P-wave axis. Participants with the greatest number of MetS components and aPWA had a higher risk of all-cause mortality (HR: 1.70, 95% CI: 1.13-2.55, P = 0.011). CONCLUSIONS: Individuals with both aPWA and MetS have a higher risk of mortality, and those with a greater number of MetS components and aPWA have a higher risk of all-cause mortality. These findings highlight the significance of integrating ECG characteristics with metabolic health status in clinical assessment.

Characteristics and utility of high-resolution optical coherence microscopy images of endocervical canal lesions.

OBJECTIVES: To investigate optical coherence microscopy (OCM) imaging features and the application value of these high-resolution images for identifying endocervical canal lesions (ECLs), which is a clinical dilemma in cervical cancer screening programs. METHODS: In total, 520 OCM images were obtained by scanning the cervical canal lesions with an ultra-high-resolution OCM system (204 specimens from 73 patients). The OCM morphologic characteristics of ECLs were observed and summarized, and then 3 researchers performed a diagnostic test of OCM images of cervical canal lesions. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value, 95% confidence interval of each parameter, and interinvestigator agreement (κ) were calculated. RESULTS: Normal endocervix, cysts, squamous metaplasia, high-grade squamous intraepithelial lesions involving glands, and invasive carcinoma had distinct OCM characteristics, which correlated well with corresponding H&E histologic sections. The accuracy, sensitivity, and specificity of the 3 researchers were 90.6%, 89.3% (95% CI, 86.5%-91.7%) and 91.6% (95% CI, 89.2%-93.5%), respectively. The positive predictive value was 90.1% (95% CI, 87.3%-92.4%), and the negative predictive value was 90.9% (95% CI, 88.5%-92.9%), with almost perfect agreement (κ = 0.874). CONCLUSIONS: The application of the OCM system in cervical canal lesions is feasible and could help improve detection of occult ECLs in cervical cancer screening programs. This study lays the foundation for further research on OCM in cervical canal lesions in vivo, which also has a potential impact on projecting pathologic evaluation beyond what is currently possible, perhaps globally.

Conversion surgery intervention versus continued systemic therapy in patients with a response after PD-1/PD-L1 inhibitor-based combination therapy for initially unresectable biliary tract cancer: a retrospective cohort study.

BACKGROUND: The role of conversion surgery in patients with unresectable biliary tract cancer (BTC) who responded positively to PD-1/PD-L1 inhibitor-based therapy remains unclear. This study aimed to assess the outcomes in patients with or without conversion surgery. METHODS: In this cohort study, patients with advanced BTC who received combination therapy with PD-1/PD-L1 inhibitors from July 2019 to January 2023 were retrospectively. Patients who exhibited positive responses and met the criteria for conversion surgery were enrolled, and their surgical and oncological outcomes were analyzed. RESULTS: Out of 475 patients, 34 who met the conversion resection criteria were enrolled. The median follow-up was 40.5 months post-initiation of systemic therapy. Ultimately, 13 patients underwent conversion surgery, while 21 received continuation of systemic treatment alone (non-surgical group). The median interval from the initial antitumor therapy to surgery was 6.7 (interquartile range [IQR] 4.9-9.2) months. Survival with conversion surgery was significantly longer than the non-surgical cohort, with a median progression-free survival (PFS) (unreached vs. 12.4 mo; hazard ratio 0.17 [95% CI 0.06-0.48]; P=0.001) and overall survival (OS) (unreached vs. 22.4 mo; hazard ratio 0.28 [95% CI 0.09-0.84]; P=0.02), respectively. After a median postoperative follow-up of 32.2 months in the surgical cohort, 8 patients survived without recurrence. The estimated 3-year OS, PFS and recurrence-free survival rate in the surgical cohort were 59.9%, 59.2% and 60.6%, respectively. The R0 resection rate reached 92.3%, with 2 achieving a pathological complete response. One patient experienced a Clavien-Dindo grade 3 complication without surgery-related mortality. No serious adverse events or surgical delays were observed. Multivariate analysis indicated that conversion surgery was independently associated with OS (P=0.03) and PFS survival (P=0.003). CONCLUSION: Conversion surgery appears safe and offers survival benefits to patients responding to immune checkpoint inhibitors (ICIs)-based combinations. However, further studies are required to validate this strategy in the era of immunotherapy.

Early enteral nutrition with exclusive donor milk instead of formula milk affects the time of full enteral feeding for very low birth weight infants.

This study investigated the effects of exclusive donor milk or formula in the first 7 days after birth, on the time to full enteral feeding, growth, and morbidity of adverse events related to premature infants. This was a retrospective study carried out from July 2014 to December 2019 at the Department of Neonatology of Shanghai Children's Hospital. All infants with a birth weight < 1,500 g and a gestational age ≤ 32 who received exclusive donor milk or formula in the first 7 days after birth were included in this study. The time to full enteral feeding (defined as 150 mL/kg) in the donor milk group was significantly shorter than in the formula group (18 vs. 22 days, p = 0.01). Donated breast milk was also associated with a lower incidence of NEC (4.4 vs. 7%, p < 0.01), ROP (3.8 vs. 13.2%, p < 0.01), and culture-confirmed sepsis (11 vs. 22.6%, p < 0.01). Using donated breast milk instead of current formula milk for early enteral nutrition can shorten the time to full enteral feeding and reduce the incidence of NEC, ROP, and sepsis.

Classification of congenital cataracts based on multidimensional phenotypes and its association with visual outcomes.

AIM: To establish a classification for congenital cataracts that can facilitate individualized treatment and help identify individuals with a high likelihood of different visual outcomes. METHODS: Consecutive patients diagnosed with congenital cataracts and undergoing surgery between January 2005 and November 2021 were recruited. Data on visual outcomes and the phenotypic characteristics of ocular biometry and the anterior and posterior segments were extracted from the patients' medical records. A hierarchical cluster analysis was performed. The main outcome measure was the identification of distinct clusters of eyes with congenital cataracts. RESULTS: A total of 164 children (299 eyes) were divided into two clusters based on their ocular features. Cluster 1 (96 eyes) had a shorter axial length (mean±SD, 19.44±1.68 mm), a low prevalence of macular abnormalities (1.04%), and no retinal abnormalities or posterior cataracts. Cluster 2 (203 eyes) had a greater axial length (mean±SD, 20.42±2.10 mm) and a higher prevalence of macular abnormalities (8.37%), retinal abnormalities (98.52%), and posterior cataracts (4.93%). Compared with the eyes in Cluster 2 (57.14%), those in Cluster 1 (71.88%) had a 2.2 times higher chance of good best-corrected visual acuity [<0.7 logMAR; OR (95%CI), 2.20 (1.25-3.81); P=0.006]. CONCLUSION: This retrospective study categorizes congenital cataracts into two distinct clusters, each associated with a different likelihood of visual outcomes. This innovative classification may enable the personalization and prioritization of early interventions for patients who may gain the greatest benefit, thereby making strides toward precision medicine in the field of congenital cataracts.

3D printing-based lateral flow visual assay utilizing the dual-excitation property of nitrogen-doped carbon dots for the ratiometric determination and chemometric discrimination of flavonoids.

A ratiometric fluorescence sensor has been established based on dual-excitation carbon dots (D-CDs) for the detection of flavonoids (morin is chosen as the typical detecting model for flavonoids). D-CDs were prepared using microwave radiation with o-phenylenediamine and melamine and exhibit controllable dual-excitation behavior through the regulation of their concentration. Remarkably, the short-wavelength excitation of D-CDs can be quenched by morin owing to the inner filter effect, while the long-wavelength excitation remains insensitive, serving as the reference signal. This contributes to the successful design of an excitation-based ratiometric sensor. Based on the distinct and differentiated variation of excitation intensity, morin can be determined from 0.156 to 110 µM with a low detection limit of 0.156 µM. In addition, an intelligent and visually lateral flow sensing device is developed for the determination  of morin content in real samples with satisfying recoveries, which indicates the potential application for human health monitoring.

Hepatic polypeptide nutrient solution improves high-cholesterol diet-induced rats with nonalcoholic fatty liver disease by activating AMP-activated protein kinase signaling pathway.

Hepatic polypeptide nutrient solution (HP) is a mixture of hepatoprotective peptides derived from fresh porcine liver with various effects. However, the role and mechanisms of HP in nonalcoholic fatty liver disease (NAFLD) are still not well understood. We investigated the effects of HP NAFLD rats induced by high-cholesterol diet (HCD) and its underlying mechanisms. Rats were provided with HCD for 4 weeks and then received HP or metformin after 2 weeks of HCD feeding. The study found that HP reduced cholesterol and triglyceride levels in rats with NAFLD (all p < .05). Histopathological examination also showed that HP improved the liver lesions induced by the HCD diet. Furthermore, the oxidative stress and inflammatory responses of NAFLD rats treated with HP were also improved. In addition, it was discovered that HP triggered the activation of AMPK and decreased the expression of SREBP-1c and FAS while enhancing the expression of PPAR α and CPT-1 in liver. These findings indicated that HP might have therapeutic potential for NAFLD, possibly via activating AMPK signaling pathway.

Dynamic alterations of flavor, functional nutrients, and microbial community during fermentation of different animal milk kefirs.

Kefir is a traditional dairy beverage, usually made from cow or goat milk fermented with kefir grains, and has many health benefits. To elucidate the fermentation patterns of animal milk kefirs during the fermentation process and find the optimal milk types, cow, camel, goat, and donkey milk were fermented with kefir grains for 0, 1, 3, 5, and 7 days. Volatile and non-volatile metabolites and microbial changes were dynamically monitored. The results showed that volatile flavor substances were massively elevated in four kefirs on days 1-3. Lipids and carbohydrates gradually decreased, while amino acids, small peptides, and tryptophan derivatives accumulated during fermentation in four kefirs. Besides, four kefirs had similar alterations in Lactobacillus and Acetobacter, while some distinctions existed in low-abundance bacteria. Association analysis of microorganisms and volatile and non-volatile metabolites also revealed the underlying fermentation mechanism. This study found that appropriately extending the fermentation time contributed to the accumulation of some functional nutrients. Furthermore, goat and donkey milk could be the better matrices for kefir fermentation.

Solar-assisted selective separation and recovery of precious group metals from deactivated air purification catalysts.

The mitigation of environmental and energy crises could be advanced by reclaiming platinum group precious metals (PGMs) from decommissioned air purification catalysts. However, the complexity of catalyst composition and the high chemical inertness of PGMs significantly impede this process. Consequently, recovering PGMs from used industrial catalysts is crucial and challenging. This study delves into an environmentally friendly approach to selectively recover PGMs from commercial air purifiers using photocatalytic redox technology. Our investigation focuses on devising a comprehensive strategy for treating three-way catalysts employed in automotive exhaust treatment. By meticulously pretreating and modifying reaction conditions, we achieved noteworthy results, completely dissolving and separating rhodium (Rh), palladium (Pd), and platinum (Pt) within a 12-h time frame. Importantly, the solubility selectivity persists despite the remarkably similar physicochemical properties of Rh, Pd, and Pt. To bolster the environmental sustainability of our method, we harness sunlight as the energy source to activate the photocatalysts, facilitating the complete dissolution of precious metals under natural light irradiation. This eco-friendly recovery approach demonstrated on commercial air purifiers, exhibits promise for broader application to a diverse range of deactivated air purification catalysts, potentially enabling implementation on a large scale.

Predicting influenza-like illness trends based on sentinel surveillance data in China from 2011 to 2019: A modelling and comparative study1.

Background: Influenza is an acute respiratory infectious disease with a significant global disease burden. Additionally, the coronavirus disease 2019 pandemic and its related non-pharmaceutical interventions (NPIs) have introduced uncertainty to the spread of influenza. However, comparative studies on the performance of innovative models and approaches used for influenza prediction are limited. Therefore, this study aimed to predict the trend of influenza-like illness (ILI) in settings with diverse climate characteristics in China based on sentinel surveillance data using three approaches and evaluate and compare their predictive performance. Methods: The generalized additive model (GAM), deep learning hybrid model based on Gate Recurrent Unit (GRU), and autoregressive moving average-generalized autoregressive conditional heteroscedasticity (ARMA-GARCH) model were established to predict the trends of ILI 1-, 2-, 3-, and 4-week-ahead in Beijing, Tianjin, Shanxi, Hubei, Chongqing, Guangdong, Hainan, and the Hong Kong Special Administrative Region in China, based on sentinel surveillance data from 2011 to 2019. Three relevant metrics, namely, Mean Absolute Percentage Error (MAPE), Root Mean Squared Error (RMSE), and R squared, were calculated to evaluate and compare the goodness of fit and robustness of the three models. Results: Considering the MAPE, RMSE, and R squared values, the ARMA-GARCH model performed best, while the GRU-based deep learning hybrid model exhibited moderate performance and GAM made predictions with the least accuracy in the eight settings in China. Additionally, the models' predictive performance declined as the weeks ahead increased. Furthermore, blocked cross-validation indicated that all models were robust to changes in data and had low risks of overfitting. Conclusions: Our study suggested that the ARMA-GARCH model exhibited the best accuracy in predicting ILI trends in China compared to the GAM and GRU-based deep learning hybrid model. Therefore, in the future, the ARMA-GARCH model may be used to predict ILI trends in public health practice across diverse climatic zones, thereby contributing to influenza control and prevention efforts.

ROS-mediated NRF2/p-ERK1/2 signaling-involved mitophagy contributes to macrophages activation induced by CdTe quantum dots.

Cadmium telluride (CdTe) quantum dots (QDs) have garnered significant attention for tumor imaging due to their exceptional properties. However, there remains a need for further investigation into their potential toxicity mechanisms and corresponding enhancements. Herein, CdTe QDs were observed to accumulate in mouse liver, leading to a remarkable overproduction of IL-1ß and IL-6. Additionally, there was evidence of macrophage infiltration and activation following exposure to 12.5 µmol/kg body weight of QDs. To elucidate the underlying mechanism of macrophage activation, CdTe QDs functionalized with 3-mercaptopropionic acid (MPA) were utilized. In vitro experiments revealed that 1.0 µM MPA-CdTe QDs activated PINK1-dependent mitophagy in RAW264.7 macrophages. Critically, the autophagic flux remained unimpeded, as demonstrated by the absence of p62 accumulation, LC3 turnover assay results, and successful fusion of autophagosomes with lysosomes. Mechanically, QDs increased reactive oxygen species (ROS) and mitoROS by damaging both mitochondria and lysosomes. ROS, in turn, inhibited NRF2, resulting in the phosphorylation of ERK1/2 and subsequent activation of mitophagy. Notably, 1.0 µM QDs disrupted lysosomes but autophagic flux was not impaired. Eventually, the involvement of the ROS-NRF2-ERK1/2 pathway-mediated mitophagy in the increase of IL-1ß and IL-6 in macrophages was confirmed using Trolox, MitoTEMPO, ML385, specific siRNAs, and lentivirus-based interventions. This study innovatively revealed the pro-inflammatory rather than anti-inflammatory role of mitophagy in nanotoxicology, shedding new light on the mechanisms of mitochondrial disorders induced by QDs and identifying several molecular targets to comprehend the toxicological mechanisms of CdTe QDs.

Long-term combined blockade of CXCR4 and PD-L1 with in vivo reassembly for intensive tumor interference.

Negative immunoregulatory signal (PD-L1, CXCR4, et al.) and weak immunogenicity elicited immune system failing to detect and destroy cancerous cells. CXCR4 blockade promoted T cell tumor infiltration and increased tumor sensitivity to anti-PD-L1 therapy. Here, pH-responsive reassembled nanomaterials were constructed with anti-PD-L1 peptide and CXCR4 antagonists grafting (APAB), synergized with photothermal therapy for melanoma and breast tumor interference. The self-assembled APAB nanoparticles accumulated in the tumor and rapidly transformed into nanofibers in response to the acidic tumor microenvironment, leading to the exposure of grafted therapeutic agents. APAB enabling to reassemble around tumor cells and remained stable for over 96 h due to the aggregation induced retention (AIR) effect, led to long-term efficiently combined PD-L1 and CXCR4 blockade. Photothermal efficiency (ICG) induced immunogenic cell death (ICD) of tumor cells so as to effectively improve the immunogenicity. The combined therapy (ICG@APAB) could effectively inhibit the growth of primary tumor (∼83.52%) and distant tumor (∼76.24%) in melanoma-bearing mice, and significantly (p < 0.05) prolong the survival time over 42 days. The inhibition assay on tumor metastasis in 4 T1 model mice exhibited ICG@APAB almostly suppressed the occurrence of lung metastases and the expression levels of CD31, MMP-9 and VEGF in tumor decreased by 82.26%, 90.45% and 41.54%, respectively. The in vivo reassembly strategy will offer novel perspectives benefical future immunotherapies and push development of combined therapeutics into clinical settings.

Effects of concurrent chemoradiotherapy with or without Endostar on the regression of retropharyngeal lymph node and prognosis of patients with locally advanced nasopharyngeal carcinoma: a retrospective study.

BACKGROUND AND PURPOSE: To investigate the effect of combining Endostar with concurrent chemoradiotherapy (ECCRT) compared to concurrent chemoradiotherapy (CCRT) on the regression rate of retropharyngeal lymph nodes (RLNs) and the relationship between regression rate of RLNs and prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS: A total of 122 LANPC patients with RLNs metastasis were included. Metastatic RLNs were delineated both before and after treatment slice by slice on the magnetic resonance images cross-section. The regression rate of RLNs, adverse effects (AE) were evaluated. The median regression rate of RLNs was taken as the cut-off value, and the patients were furtherly divided into high regression rate (HRR) group and low regression rate (LRR) group, then survival times were evaluated. RESULTS: The median regression rates of RLNs in the ECCRT and CCRT groups were 81% and 50%, respectively (P < 0.001). There was no statistically significant difference in the incidence of grade 3/4 AEs between the two groups, except for oral mucositis (ECCRT 26.23% vs. CCRT 44.26%, P = 0.037). The 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional failure-free survival (LRFFS) rates in the HRR and LRR groups were 85.48% and 86.67% (P = 0.983), 80.65% and 68.33% (P = 0.037), 83.87% and 85% (P = 0.704), 93.55% and 81.67% (P = 0.033), respectively. CONCLUSIONS: Patients in the ECCRT group had higher regression rates of RLNs and lower incidence of severe oral mucositis. Furthermore, patients in the HRR group had a better 3-year PFS and LRFFS rate than those in the LRR group.

The deubiquitinating enzyme USP4 regulates BRCA1 stability and function.

BRCA1 plays a suppressive role in breast tumorigenesis. Ubiquitin-dependent degradation is a common mechanism that regulates BRCA1 protein stability, and several ubiquitin ligases involved have been identified. However, the deubiquitinating enzyme for BRCA1 remains less defined. Here, we report that the deubiquitinase USP4 interacts with, deubiquitinates and stabilizes BRCA1, maintaining the protein level of BRCA1. USP4 knockdown results in a decreased BRCA1 protein level, impairment in homologous recombination mediated double-stranded break repair, and increased genome instability, and confers resistance to DNA damage-inducing agents and PARP inhibitors. Ectopic expression of USP4 stabilizes BRCA1 and reverse the effects caused by USP4 knockdown. Moreover, USP4 is low expressed in human breast cancer tissues and its low expression correlates with poorer survival of patients. Furthermore, we identified several loss-of-function mutations of USP4 in human gynecological cancers, the catalytic activity of which or their interaction with BRCA1 is disrupted. Together, we reveal that USP4 is a deubiquitinase for BRCA1. USP4 positively regulates the stability and function of BRCA1 through de-ubiquitination, and plays important role in the suppression of breast cancer.

Influence of circadian rhythm and sleep schedules on depressive symptoms among adolescents in China.

Circadian rhythm (24-hour period of physiological and behavioral changes) is the basis of the overall health, including mood and health. This study aimed to explore the influence of circadian rhythm and sleep schedules on depressive symptoms in Chinese adolescents. In this cross-sectional study, 841 middle school students were recruited and divided into two groups (depressive group, DG, n = 210, and control group, n = 631) depending on the total score of The Center for Epidemiological Studies Depression Scale for Children (CES-DC). The circadian rhythm and sleep quality among adolescents were evaluated by using the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) and Self-rating scale of Sleep (SRSS) scales. Furthermore, correlation analysis and logistic regression analysis were used to determine the effects of demographic factors, sleeping arrangement, sleep quality, and circadian rhythm on depressive symptoms. The DG group's CES-DC, BRIAN and SRSS scores were significantly higher than the control group's. Higher scores of BRIAN and SRSS were risk factors for depressive symptoms in Chinese adolescents. Attending a day school and waking up later on weekends may be weak protective factors. Our results suggest that circadian rhythm disturbance, sleep quality, and sleeping arrangement have a significant influence on depressive symptoms among adolescents in China.

Accumulation rate and sources of plastic marine litter at nesting grounds of green turtles on the North Island of Qilianyu, Xisha Islands, South China Sea.

In this study, the accumulation rate of plastic litter was investigated by sampling quadrats placed on the North Island of Qilianyu, and the composition was analyzed and identified to determine its source. The results showed that the annual average accumulation rate of plastic litter on North Island was 0.64 ± 0.32 pieces·m-2·month-1, with a mass accumulation rate of 11.30 ± 7.73 g·m-2·month-1. The accumulation rate of plastic litter was mainly influenced by wind speed and direction, with higher accumulation rates occurring during the southwest monsoon season and tropical cyclones. ATR-FTIR analysis indicated that polyethylene (44 %) and polypropylene (41 %) were the most abundant types of polymers. This study reveals the current status of plastic litter pollution in green turtle nesting grounds on North Island in Qilianyu, which can be used as a reference for management strategies that mitigate plastic litter pollution.

CD73 polymorphisms are associated with schizophrenia.

Ecto-5'-nucleotidase/CD73 enzyme plays a key role in the regulation of extracellular adenosine levels, thereby exerting influence on adenosine homeostasis. Emerging evidence suggests that perturbations in purines and ecto-5'-nucleotidase activity are associated with an augmented susceptibility to schizophrenia. However, the precise impact of genetic variations in CD73 on individuals with schizophrenia remains poorly understood. Here, our study demonstrated that rs3734442 allele and rs4431401 heterozygote were conferred a significant risk of schizophrenia disease (rs3734442: odds ratio, 0.556; 95% CI, 0.375 to 0.825; p = 0.004; rs4431401: odds ratio, 1.881, 95% CI, 1.117 to 3.166; p = 0.020). Comparing different genders, we observed a significant association between rs3734442 genotypes and male cases (rs3734442: odds ratio, 0.452; 95% CI, 0.257 to 0.796; p = 0.007). Likewise, there was a significant association between rs4431401 genotypes and male patients (rs4431401: odds ratio, 2.570; 95% CI, 1.196 to 5.522; p = 0.015). Based on family history and antipsychotics medication usage, our data reveals that the rs9444348 allele exhibits the most significant association with familial susceptibility to schizophrenia (odds ratio, 1.541; 95% CI, 1.009 to 2.353; p = 0.048 for A vs G). Moreover, individuals carrying variants of rs6922, rs2229523, and rs2065114 while being treated with clozapine demonstrate a higher frequency proportion compared to those receiving risperidone treatment (p = 0.035; p = 0.049; p = 0.027 respectively). Additionally, our results indicate that patients with GG genotype of rs9444348 had significantly higher likelihood of using clozapine instead of sulpiride (p = 0.048). Overall, our data strongly suggest that genetic variations in CD73 are significantly associated with schizophrenia risk and may serve as valuable resources for identifying therapeutic targets.