The longitudinal patterns of depression subtypes and stressors in depression severity in the Canadian longitudinal study on aging (CLSA).

AIM: The current study aims to characterize the longitudinal patterns of depression subtypes and investigate the associations among the stability of depression subtypes, COVID-19-related stressors, and depression severity. METHODS: The study utilized data from the Canadian Longitudinal Study on Aging, which is a national, long-term study of Canadian adults aged 45 and older (n = 12,957). Latent profile analysis was used to identify latent depression subtypes. Latent transition analysis was then applied to assess the stability of these subtypes over time. Hierarchical multivariate linear regression was used to explore the relationships among these identified depression subtypes, COVID-19-related stressors, and depression severity among males and females, respectively. RESULTS: Distinct depression subtypes were identified. Except for atypical depression, other depression subtypes showed greater stability over time. We also found that melancholic depression (B = 9.432) and typical depression (B = 6.677) were strongly associated with depression severity during the pandemic. Health-related stressors (B = 0.840), conflict (B = 3.639), difficulties accessing resources (B = 0.927), separation from family (B = 0.840), and caregiving experience (B = 0.764), were significantly associated with increased depression severity. Sex-specific analyses also revealed differences in the associations between stressors and depression severity between males and females. CONCLUSIONS: This study contributes valuable insights into the latent clustering of depression subtypes and their stability. Stressors were associated with increased depression severity, with distinct associations observed among males and females. These findings have implications for targeted early interventions and integrated clinical management strategies by providing the evidence base for tailored mental health care during and after the pandemic.

Characterization of a ferroptosis-related gene signature predicting survival and immunotherapeutic response in lung adenocarcinoma.

Lung cancer remains the leading cause of cancer-related death worldwide, and drug resistance represents the main obstacle responsible for the poor mortality and prognosis. Here, to identify a novel gene signature for predicting survival and drug response, we jointly investigated RNA sequencing data of lung adenocarcinoma patients from TCGA and GEO databases, and identified a ferroptosis-related gene signature. The signature was validated in the validation set and two external cohorts. The high-risk group had a reduced survival than the low-risk group (P < 0.05). Moreover, the established gene signature was associated with tumor mutation burden, microsatellite instability, and response to immune checkpoint blockade. In addition, four candidate oncogenes (RRM2, SLC2A1, DDIT4, and VDAC2) were identified to be candidate oncogenes using in silico and wet experiments, which could serve as potential therapeutic targets. Collectively, this study developed a novel ferroptosis-related gene signature for predicting prognosis and drug response, and identified four candidate oncogenes for lung adenocarcinoma.

Identification of diagnostic biomarkers and immune cell infiltration in tongue squamous cell carcinoma using bioinformatic approaches.

OBJECTIVE: In this study, we employed a bioinformatics approach to identify diagnostic biomarkers for tongue squamous cell carcinoma (TSCC) and investigate the infiltration of immune cells in TSCC, as well as the relationship between biomarkers and immune cells. METHODS: We obtained the TSCC expression dataset from a database and conducted differential gene expression analysis between TSCC and adjacent normal tissues using R software. Enrichment analysis of the differentially expressed genes (DEGs) was performed using the DAVID website. Protein interaction networks for the DEGs were constructed, and hub genes were identified using tools such as STRING and Cytoscape. Survival analysis was conducted to identify diagnostic biomarkers and the infiltration of immune cells in TSCC was analyzed using the inverse convolution algorithm with Cibersort software. Finally, the expression of the discovered molecules was verified through clinical pathological sections. RESULTS: We identified 24 DEGs in TSCC, primarily associated with signal transduction, substance metabolism, innate immune response, and other related signaling pathways. Among the 24 hub genes screened through the construction of a protein-protein interaction (PPI) network, seven (MMP13, POSTN, MMP9, MMP10, MMP3, SPP1, MMP1) exhibited prognostic value. Survival analysis indicated that SPP1 demonstrated diagnostic potential. The expression level of the SPP1 gene showed a correlation with TSCC as well as several immune cell types, including macrophage M0, M1, M2, CD8+ T cell, activated NK cell, and monocyte (p < 0.05). Histological results confirmed higher expression of SPP1 in TSCC tissues compared to adjacent non-cancerous tissues, particularly in CD68-expressing macrophages. CONCLUSION: Our findings suggest that SPP1 serves as a diagnostic biomarker for TSCC and is involved in immune cell infiltration within TSCC tissues. The correlation between SPP1 and macrophages may offer new insights for targeted therapeutic research on TSCC.

Delayed Bladder Perforation Resulting From Large Bladder Stone and Gluteal Abscess Caused by Pelvic Plate Loosening: A Case Report.

Delayed bladder injuries resulting from screw or plate loosening, following pelvic ring fractures are rare, and this complication could be prevented. A 63-year-old woman presented with dysuria and lower abdominal pain, 13 years after the open fixation of a pelvic injury. Computed tomography revealed a 5-cm bladder stone and two migrated screws. Six months after the stone was removed, an abscess was noted over the left gluteal region. During the removal of the screw and abscess debridement, we accidentally observed that the anterior pelvic bridge plate had eroded into the bladder and had multiple bladder stones attached. After the involved hardware was removed, the abscess was debrided and the bladder was repaired. The patient did not have further urinary tract infections or urinary symptoms. In patients with pelvic ring fractures, we recommend placing the bridge plate on the superior side of the pubic symphysis to reduce the risk of bladder perforation in the event of plate or screw loosening. When a patient with a history of pelvic fixation presents with symptoms such as urinary tract infections, bladder stones, or even an abscess around the gluteal region, possible bladder perforation caused by the loosening of plates or screws should be considered.

The association of diabetes with progression of sleep-disordered breathing based on a prospective cohort.

AIM: Prospective studies suggest that sleep-disordered breathing enhances the risk of diabetes. However, it remains unclear whether diabetes could worsen sleep-disordered breathing. METHODS: The participants from Sleep Heart Health Study underwent two polysomnograms at a 5-year interval. The relationship of baseline diabetes to change in the apnoea-hypopnoea index (AHI) was examined based on general linear models, adjusting for demographics, lifestyles, history of hypertension, pulmonary function, length of follow-up and baseline AHI. RESULTS: In total, 161 of the 2603 participants were diagnosed with diabetes at the first polysomnograms. Compared with participants without diabetes, those with diabetes had a higher baseline and larger increases in follow-up AHI and obstructive apnoea index (oAI). Diabetes increased 2.52 events per hour (95% confidence interval 0.45-4.59; p = .017) for AHI change and 1.13 events per hour (95% confidence interval 0.04-2.23; p = .042) for oAI change, respectively. In addition, subgroup analysis suggested that the association was consistent across baseline obstructive sleep apnoea severity and body mass index groups. CONCLUSIONS: Baseline diabetes was associated with worsening sleep-disordered breathing over 5 years, which mainly increased the change in AHI and oAI.

Differential interactions between gene expressions and stressors across the lifespan in major depressive disorder.

BACKGROUND: Both genetic predispositions and exposures to stressors have collectively contributed to the development of major depressive disorder (MDD). To deep dive into their roles in MDD, our study aimed to examine which susceptible gene expression interacts with various dimensions of stressors in the MDD risk among a large population cohort. METHODS: Data analyzed were from a longitudinal community-based cohort from Southwest Montreal, Canada (N = 1083). Latent profile models were used to identify distinct patterns of stressors for the study cohort. A transcriptome-wide association study (TWAS) method was performed to examine the interactive effects of three dimensions of stressors (threat, deprivation, and cumulative lifetime stress) and gene expression on the MDD risk in a total of 48 tissues from GTEx. Additional analyses were also conducted to further explore and specify these associations including colocalization, and fine-mapping analyses, in addition to enrichment analysis investigations based on TWAS. RESULTS: We identified 3321 genes linked to MDD at the nominal p-value <0.05 and found that different patterns of stressors can amplify the genetic susceptibility to MDD. We also observed specific genes and pathways that interacted with deprivation and cumulative lifetime stressors, particularly in specific brain tissues including basal ganglia, prefrontal cortex, brain amygdala, brain cerebellum, brain cortex, and the whole blood. Colocalization analysis also identified these genes as having a high probability of sharing MDD causal variants. LIMITATIONS: The study cohort was composed exclusively of individuals of Caucasians, which restricts the generalizability of the findings to other ethnic population groups. CONCLUSIONS: The findings of the study unveiled significant interactions between potential tissue-specific gene expression × stressors in the MDD risk and shed light on the intricate etiological attributes of gene expression and specific stressors across the lifespan in MDD. These genetic and environmental attributes in MDD corroborate the vulnerability-stress theory and direct future stress research to have a closer examination of genetic predisposition and potential involvements of omics studies to specify the intricate relationships between genes and stressful environments.

Deciphering the mechanism of E3 ubiquitin ligases in plant responses to abiotic and biotic stresses and perspectives on PROTACs for crop resistance.

With global climate change, it is essential to find strategies to make crops more resistant to different stresses and guarantee food security worldwide. E3 ubiquitin ligases are critical regulatory elements that are gaining importance due to their role in selecting proteins for degradation in the ubiquitin-proteasome proteolysis pathway. The role of E3 Ub ligases has been demonstrated in numerous cellular processes in plants responding to biotic and abiotic stresses. E3 Ub ligases are considered a class of proteins that are difficult to control by conventional inhibitors, as they lack a standard active site with pocket, and their biological activity is mainly due to protein-protein interactions with transient conformational changes. Proteolysis-targeted chimeras (PROTACs) are a new class of heterobifunctional molecules that have emerged in recent years as relevant alternatives for incurable human diseases like cancer because they can target recalcitrant proteins for destruction. PROTACs interact with the ubiquitin-proteasome system, principally the E3 Ub ligase in the cell, and facilitate proteasome turnover of the proteins of interest. PROTAC strategies harness the essential functions of E3 Ub ligases for proteasomal degradation of proteins involved in dysfunction. This review examines critical advances in E3 Ub ligase research in plant responses to biotic and abiotic stresses. It highlights how PROTACs can be applied to target proteins involved in plant stress response to mitigate pathogenic agents and environmental adversities.

Heterothermic Cataluminescence Sensor System for Efficient Determination of Aldehyde Molecules.

A simple and stable cataluminescence (CTL) sensing platform based on a single sensing material for effective and rapid detection of aldehydes is an urgent need due to growing concerns for the environment, security, and health. Here, an effective and user-friendly identification method is successfully proposed to determine six common aldehydes of homologous compounds via a heterothermic CTL sensor system. Using Gd2O3 with excellent catalytic activity as a sensing material, thermodynamic and kinetic insights into the interactions between Gd2O3 and aldehydes at different temperatures were extracted and integrated to generate a unique constellation profile for each tested aldehyde, whereby achieving their effective and prompt determination. Moreover, the sensor system allowed the quantitative analysis of aldehydes with detection limits of 0.001, 0.009, 0.011, 0.011, 0.007, and 0.003 µg mL-1. Significantly, the sensor system had an excellent stability of up to 30 days. The CTL sensing platform was constructed based on a thermal regulation strategy that can provide a new approach to chemical agent identification.

Quantitative EEG reactivity induced by electrical stimulation predicts good outcome in comatose patients after cardiac arrest.

BACKGROUND: EEG reactivity is a predictor for neurological outcome in comatose patients after cardiac arrest (CA); however, its application is limited by variability in stimulus types and visual assessment. We aimed to evaluate the prognostic value of the quantitative analysis of EEG reactivity induced by standardized electrical stimulation and for early prognostication in this population. METHODS: This prospective observational study recruited post-CA comatose patients in Xuanwu Hospital, Capital Medical University (Beijing, China) between January 2016 and June 2023. EEG reactivity to electrical or traditional pain stimulation was randomly performed via visual and quantitative analysis. Neurological outcome within 6 months was dichotomized as good (Cerebral Performance Categories, CPC 1-2) or poor (CPC 3-5). RESULTS: Fifty-eight post-CA comatose patients were admitted, and 52 patients were included in the final analysis, of which 19 (36.5%) had good outcomes. EEG reactivity induced with the electrical stimulation had superior performance to the traditional pain stimulation for good outcome prediction (quantitative analysis: AUC 0.932 vs. 0.849, p = 0.048). When using the electrical stimulation, the AUC of EEG reactivity to predict good outcome by visual analysis was 0.838, increasing to 0.932 by quantitative analysis (p = 0.039). Comparing to the traditional pain stimulation by visual analysis, the AUC of EEG reactivity for good prognostication by the electrical stimulation with quantitative analysis was significantly improved (0.932 vs. 0.770, p = 0.004). CONCLUSIONS: EEG reactivity induced by the standardized electrical stimulation in combination with quantitative analysis is a promising formula for post-CA comatose patients, with increased predictive accuracy.

Active surveillance of hepatitis E: a 10-year epidemiological analysis in a city in eastern China.

Hepatitis E virus (HEV) is an important cause of acute hepatitis, however, is highly neglected and largely underreported. This study aimed to describe the detailed epidemiology of hepatitis E (HE) through a 10-year surveillance. A community-based active hepatitis surveillance was conducted between November 2007 and October 2017 in 11 townships of Dongtai City in China, involving 355,673 residents. Serum samples were obtained from patients presenting with hepatitis symptoms for more than 3 days. Serum alanine aminotransferase (ALT) levels greater than 2.5 times the upper limit of normal (ULN) were considered acute hepatitis. Samples were subsequently tested for IgG and IgM anti-HEV antibodies, HEV RNA, and hepatitis B surface antigen (HBsAg). The data indicated the incidence of HE fluctuated downward from 2007 to 2017, with an average annual age-standardized incidence of 17.50 per 100,000, exceeding the 10.26 per 100,000 in the National Notifiable Disease Report System (NNDRS). The incidence was notably higher among males (20.95 per 100,000) and individuals aged 50-69 years (37.47 per 100,000). Genotype 4 (HEV-4) was the predominantly circulating genotype during the study period. Furthermore, the study revealed the incidence of hepatitis with HEV and hepatitis B virus (HBV) co-infection was 4.99 per 100,000. The active surveillance system identified a higher incidence of HE compared to NNDRS, with a decreased prevalence over a 10-year period. While efforts are still needed to prevent HE in high-risk populations, including individuals with hepatitis B and the elderly.

Recent advances in the multifaceted functions of Cys2/His2-type zinc finger proteins in plant growth, development, and stress responses.

Recent research has highlighted the importance of Cys2/His2-type zinc finger proteins (C2H2-ZFPs) in plant growth and in responses to various stressors, and the complex structures of C2H2-ZFP networks and the molecular mechanisms underlying their responses to stress have received considerable attention. Here, we review the structural characteristics and classification of C2H2-ZFPs, and consider recent research advances in their functions. We systematically introduce the roles of these proteins across diverse aspects of plant biology, encompassing growth and development, and responses to biotic and abiotic stresses, and in doing so hope to lay the foundations for further functional studies of C2H2-ZFPs in the future.

Characterization of depression subtypes and their relationships to stressor profiles among middle-aged and older adults: An analysis of the canadian longitudinal study on aging (CLSA).

The current diagnostic criteria for depression do not sufficiently reflect its heterogeneous clinical presentations. Associations between adverse childhood experiences (ACEs), allostatic load (AL), and depression subtypes have not been extensively studied. Depression subtypes were determined based on clinical presentations, and their relationships to AL biomarkers and ACEs were elucidated in a sample of middle-aged and older adults. Participants from the Canadian Longitudinal Study on Aging who screened positive for depression were included (n = 3966). Depression subtypes, AL profiles and ACE profiles were determined with latent profile analyses, and associations between them were determined using multinomial logistic regression. Four depression subtypes were identified: positive affect, melancholic, typical, and atypical. Distinct associations between depression subtypes, stressor profiles and covariates were observed. Among the subtypes compared to positive affect, atypical subtype had the most numerous significant associations, and the subtypes had unique relationships to stressor profiles. Age, sex, smoking status, chronic conditions, marital status, and physical activity were significant covariates. The present study describes distinct associations between depression subtypes and measures of stress (objective and self-reported), as well as related factors that differentiate subtypes. The findings may inform more targeted and integrated clinical management strategies for depression in individuals exposed to multiple stressors.

Persistent Luminescence Lifetime-Based Near-Infrared Nanoplatform via Deep Learning for High-Fidelity Biosensing of Hypochlorite.

In light of deep tissue penetration and ultralow background, near-infrared (NIR) persistent luminescence (PersL) bioprobes have become powerful tools for bioapplications. However, the inhomogeneous signal attenuation may significantly limit its application for precise biosensing owing to tissue absorption and scattering. In this work, a PersL lifetime-based nanoplatform via deep learning was proposed for high-fidelity bioimaging and biosensing in vivo. The persistent luminescence imaging network (PLI-Net), which consisted of a 3D-deep convolutional neural network (3D-CNN) and the PersL imaging system, was logically constructed to accurately extract the lifetime feature from the profile of PersL intensity-based decay images. Significantly, the NIR PersL nanomaterials represented by Zn1+xGa2-2xSnxO4: 0.4 % Cr (ZGSO) were precisely adjusted over their lifetime, enabling the PersL lifetime-based imaging with high-contrast signals. Inspired by the adjustable and reliable PersL lifetime imaging of ZGSO NPs, a proof-of-concept PersL nanoplatform was further developed and showed exceptional analytical performance for hypochlorite detection via a luminescence resonance energy transfer process. Remarkably, on the merits of the dependable and anti-interference PersL lifetimes, this PersL lifetime-based nanoprobe provided highly sensitive and accurate imaging of both endogenous and exogenous hypochlorite. This breakthrough opened up a new way for the development of high-fidelity biosensing in complex matrix systems.

Immunogenicity and safety of an ORF7-deficient skin-attenuated and neuro-attenuated live vaccine for varicella: a randomised, double-blind, controlled, phase 2a trial.

BACKGROUND: The Oka varicella vaccine strain remains neurovirulent and can establish lifelong latent infection, raising safety concerns about vaccine-related herpes zoster. In this study, we aimed to evaluate the immunogenicity and safety of a skin-attenuated and neuro-attenuated varicella vaccine candidate (v7D vaccine). METHODS: We did this randomised, double-blind, controlled, phase 2a clinical trial in Jiangsu, China. Healthy children aged 3-12 years with no history of varicella infection or vaccination were enrolled and randomly assigned (1:1:1:1) to receive a single subcutaneous injection of the v7D vaccine at 3·3 log10 plaque forming units (PFU; low-dose v7D group), 3·9 log10 PFU (medium-dose v7D group), and 4·2 log10 PFU (high-dose v7D group), or the positive control varicella vaccine (vOka vaccine group). All the participants, laboratory personnel, and investigators other than the vaccine preparation and management staff were masked to the vaccine allocation. The primary outcome was assessment of the geometric mean titres (GMTs) and seroconversion rates of anti-varicella zoster virus immunoglobulin G (IgG) induced by different dose groups of v7D vaccine at 0, 42, 60, and 90 days after vaccination in the per-protocol set for humoral immune response analysis. Safety was a secondary outcome, focusing on adverse events within 42 days post-vaccination, and serious adverse events within 6 months after vaccination. This study was registered on Chinese Clinical Trial Registry, ChiCTR2000034434. FINDINGS: On Aug 18-21, 2020, 842 eligible volunteers were enrolled and randomly assigned treatment. After three participants withdrew, 839 received a low dose (n=211), middle dose (n=210), or high dose (n=210) of v7D vaccine, or the vOka vaccine (n=208). In the per-protocol set for humoral immune response analysis, the anti-varicella zoster virus IgG antibody response was highest at day 90. At day 90, the seroconversion rates of the low-dose, medium-dose, and high-dose groups of v7D vaccine and the positive control vOka vaccine group were 100·0% (95% CI 95·8-100·0; 87 of 87 participants), 98·9% (93·8-100·0; 87 of 88 participants), 97·8% (92·4-99·7; 91 of 93 participants), and 96·4% (89·8-99·2; 80 of 83 participants), respectively; the GMTs corresponded to values of 30·8 (95% CI 26·2-36·0), 31·3 (26·7-36·6), 28·2 (23·9-33·2), and 38·5 (31·7-46·7). The v7D vaccine, at low dose and medium dose, elicited a humoral immune response similar to that of the vOka vaccine. However, the high-dose v7D vaccine induced a marginally lower GMT compared with the vOka vaccine at day 90 (p=0·027). In the per-protocol set, the three dose groups of the v7D vaccine induced a similar humoral immune response at each timepoint, with no statistically significant differences. The incidence of adverse reactions in the low-dose, medium-dose, and high-dose groups of v7D vaccine was significantly lower than that in the vOka vaccine group (17% [35 of 211 participants], 20% [41 of 210 participants], and 13% [27 of 210 participants] vs 24% [50 of 208 participants], respectively; p=0·025), especially local adverse reactions (10% [22 of 211 participants], 14% [30 of 210 participants] and 9% [18 of 210 participants] vs 18% [38 of 208 participants], respectively; p=0·016). None of the serious adverse events were vaccine related. INTERPRETATION: The three dose groups of the candidate v7D vaccine exhibit similar humoral immunogenicity to the vOka vaccine and are well tolerated. These findings encourage further investigations on two-dose vaccination schedules, efficacy, and the potential safety benefit of v7D vaccine in the future. FUNDING: The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, the Fundamental Research Funds for the Central Universities, and Beijing Wantai. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Bisphenol A and selenium deficiency exposure induces pyroptosis and myogenic differentiation disorder in chicken muscle stomach.

Bisphenol A (BPA), which is commonly found in the environment due to its release from the use of plastics and food overpacks, has become a major stressor for environmental sustainability and livestock and poultry farming health. Selenium (Se) deficiency causes structural damage and inflammatory responses to the digestive system and muscle tissue, and there is a potential for concurrent space-time exposure to nutritional deficiency diseases and environmental toxicants in livestock and poultry. The mechanisms of damage to chicken muscular stomach from BPA or/and Se deficiency treatment are still not known. Here, we established a chicken model of BPA (20 mg/kg) or/and Se deficiency (0.039 mg/kg) exposure, and detected histopathological changes in the muscular stomach tissue, the levels of iNOS/NO pathway, IL-6/JAK/STAT3 pathway, pyroptosis, and myogenic differentiation by H&E staining, immunofluorescence staining, real-time quantitative PCR, and western blot methods. The data revealed that BPA or Se deficiency exposure caused gaps between muscle fibers with inflammatory cell infiltration; up-regulation of the iNOS/NO pathway and IL-6/JAK/STAT3 pathway; up-regulation of NLRP3/Caspase-1-dependent pyroptosis related genes; down-regulation of muscle-forming differentiation (MyoD, MyoG, and MyHC) genes. The combination of BPA and Se deficiency was associated with higher toxic impairment than alone exposure. In conclusion, we discovered that BPA and Se deficiency caused myogastric pyroptosis and myogenic differentiation disorder. These findings provide a theoretical basis for the co-occurrence of animal nutritional deficiency diseases and environmental toxicant exposures in livestock and poultry farming, and may provide important insights into limiting the production of harmful substances.

The development of the neurocritical care specialty in China based on the analysis of neurocritical care unit volume and quality.

PURPOSE: Through three neurocritical care unit (NCCU) surveys in China, we tried to understand the development status of neurocritical care and clarify its future development. METHODS: Using a cross-sectional survey method and self-report questionnaires, the number and quality of NCCUs were investigated through three steps: administering the questionnaire, sorting the survey data, and analyzing the survey data. RESULTS: At the second and third surveys, the number of NCCUs (76/112/206) increased by 47% and 84%, respectively. The NCCUs were located in tertiary grade A hospitals or teaching hospitals (65/100/181) in most provinces (24/28/29). The numbers of full-time doctors (359/668/1337) and full-time nurses (904/1623/207) in the NCCUs increased, but the doctor-bed ratio and nurse-bed ratio were still insufficient (0.4:1 and 1.3:1). CONCLUSION: In the past 20 years, the growth rate of NCCUs in China has accelerated, while the allocation of medical staff has been insufficient. Although most NCCU hospital bed facilities and instruments and equipment tend to be adequate, there are obvious defects in some aspects of NCCUs.

Near-Infrared Catalytic Chemiluminescence System based on Zinc Gallate Nanoprobe for Hydrazine Sensing.

To the deep tissue penetration and ultra-low background, developing near-infrared (NIR) chemiluminescence probes for human health and environmental safety has attracted more and more attention, but it remains a huge challenge. Herein, a novel NIR chemiluminescence (CL) system was rationally designed and developed, utilizing Cr3+-activated ZnGa2O4 (ZGC) nanoparticles as a catalytic luminophore via hypochlorite (NaClO) activation for poisonous target (hydrazine, N2H4) detection. With superior optical performance and unique catalytic structure of ZGC nanoparticles, the fabricated ZGC-NaClO-N2H4 CL system successfully demonstrated excellent NIR emission centered at 700 nm, fast response, and high sensibility (limit of detection down to 0.0126 µM). Further experimental studies and theoretical calculations found the cooperative catalytic chemiluminescence resonance energy transfer mechanism in the ZGC-NaClO-N2H4 system. Remarkably, the ZGC-based NIR CL system was further employed for N2H4 detection in a complicated matrix involving bioimaging and real water samples, thereby opening a new way as a highly reliable and accurate tool in biomedical and environmental monitoring applications.

Pattern of multiple human papillomavirus infection and type competition: An analysis in healthy Chinese women aged 18-45 years.

To assess the pattern of multiple human papillomavirus infection to predict the type replacement postvaccination. A total of 7372 women aged 18-45y from a phase III trial of an Escherichia coli-produced HPV-16/18 vaccine were analyzed at enrollment visit before vaccination. Hierarchical multilevel logistic regression was used to evaluate HPV vaccine type and nonvaccine-type interactions with age as a covariate. Binary logistic regression was construed to compare multiple infections with single infections to explore the impact of multiple-type infections on the risk of cervical disease. Multiple HPV infections were observed in 25.2% of HPV-positive women and multiple infections were higher than expected by chance. Statistically significant negative associations were observed between HPV16 and 52, HPV18 and HPV51/52/58, HPV31 and HPV39/51/52/53/54/58, HPV33 and HPV52/58, HPV58 and HPV52, HPV6 and HPV 39/51/52/53/54/56/58. Multiple HPV infections increased the risk of CIN2+ and HSIL+, with the ORs of 2.27(95%CI: 1.41, 3.64) and 2.26 (95%CI: 1.29, 3.95) for multiple oncogenic HPV infection separately. However, no significant evidence for the type-type interactions on risk of CIN2+ or HSIL+. There is possibility of type replacement between several pairs of vaccine and nonvaccine HPV type. Multiple HPV infection increased the risk of cervical disease, but coinfection HPV types seem to follow independent disease processes. Continued post-vaccination surveillance for HPV 51/52/58 types and HPV 39/51 types separately was essential after the first and second generation of HPV vaccination implementation in China.

PI3K/AKT pathway modulation and cold acclimation alleviation concerning apoptosis and necroptosis in broiler thymus.

Moderate cold stimulation regulates the thymus's growth and function and facilitates cold acclimatization in broilers. However, the underlying mechanism remains unknown. To explore the possible mechanism of the thymus in cold-acclimated broilers against cold stress, 240 one-day-old Arbor Acres (AA) broilers were assigned to 2 groups randomly. The control group (C) was housed at conventional temperatures. The temperature during the first week was 33°C to 34°C. Between the ages of 8 and 32 d, the temperature was lowered by 1°C every 2 d, i.e., gradually from 32°C to 20°C, and then maintained at 20°C until 42 d of age. The cold-acclimated group (C-3) was housed at the same temperature as C from 1 to 7 d after birth. Between 8 and 42 d, the temperature of C-3 was 3°C colder than C. After 24 h exposure to acute cold stress (ACS) at 42 d, C and C-3 were named as S and S-3. The results showed that ACS was able to induce oxidation stress, modulate PI3K/AKT signal, and cause necroptosis and apoptosis in broiler thymus. By contrast, cold acclimation could alleviate apoptosis and necroptosis induced by cold stress via alleviating oxidative stress, efficiently activating the PI3K/AKT signal, as well as decreasing apoptotic and necrotic genes' levels. This study offers a novel theoretical basis for cold acclimation to improve the body's cold tolerance.

A Review on Traditional Uses, Phytochemistry, Pharmacology and Clinical Application of Tinospora sinensis (Lour.) Merr.

Tinospora sinensis (T. sinensis), whose Tibetan name is "Lezhe", as a traditional medicine, is widely distributed in China, India and Sri Lanka. It is used for the treatment of rheumatic arthralgia, sciatica, lumbar muscle strain and bruises. Research over the previous decades indicated that T. sinensis mainly contains terpenes, lignans, alkaloids, phenol glycosides and other chemical components. A wide range of pharmacologic activities such as anti-inflammatory, analgesic, immunosuppressive, anti-aging, anti-radiation, anti-leishmania and liver protection have been reported. However, the scholar's research on the pharmacodynamic material basis of T. sinensis is relatively weak. Data regarding many aspects such as links between the traditional uses and bioactivities, pharmacokinetics, and quality control standard of active compositions is still limited and need more attention. This review reports a total of 241 compounds, the ethnopharmacology and clinical application of T. sinensis, covering the literature which were searched by multiple databases including Web of Science, PubMed, Google Scholar, Science Direct, CNKI and other literature sources from 1996 to date, with a view to provide a systematic and insightful reference and lays a foundation and inspiration for the application and further in-depth research of T. sinensis resources.