Sexual difficulties in men who have sex with men living with HIV: their mental health and health-related quality of life.

Background: Health-related quality of life (HRQoL) is gaining significance for people living with human immunodeficiency virus (HIV), with sexual difficulties being a crucial yet frequently neglected component of HRQoL, especially in HIV-positive men who have sex with men (MSM). Aim: The study sought to assess the levels of sexual difficulties and explore the associations between sexual difficulties, mental health, and HRQoL in HIV-positive MSM. Methods: A cohort of 475 HIV-positive MSM was studied from January 2017 to December 2021. Sociodemographic, clinical, and lifestyle data were collected. Participants were divided based on Arizona Sexual Experience Scale (ASEX) scores into 2 groups: those with sexual difficulties and a control group without difficulties. Outcomes: Psychological symptoms were evaluated by the Symptom Checklist-90 (SCL-90), HRQoL was accessed via 36-item Short Form Health Survey, and sexual function was assessed using the ASEX. We also employed path analysis to unveil latent mechanisms, alongside multivariate analysis to identify independent factors, and aimed to elucidate the interplay among sexual function, HRQoL, and mental health in HIV-positive MSM. Results: A total of 391 HIV-positive MSM were enrolled in the control group and 84 in the sexual difficulties group. The control group had significantly higher physical HRQoL (P = .004) and mental HRQoL (P = .045). In addition, SCL-90 scores were higher in the sexual difficulties group (P = .001). Multivariate analyses that indicated regular exercise (odds ratio, 0.553; P = .024) and alcohol consumption (odds ratio, 1.780; P = .033) were independent factors associated with sexual difficulties. The proportion of alcohol consumption in the sexual difficulties group was significantly higher (P = .003). ASEX scores increased gradually with increasing frequency of alcohol consumption (P = .031). Results from structural equation model showed a negative association between HRQoL and ASEX scores (ß = -0.13, P < .001) and SCL-90 scores (ß = -0.40, P < .001). Clinical Implications: HIV-positive MSM experiencing sexual difficulties exhibited lower HRQoL and worse mental health, with independent associations identified for regular exercise and alcohol consumption in relation to sexual difficulties. Strengths and Limitations: Our research has pioneered in demonstrating that HRQoL mediates the relationship between sexual difficulties and psychological symptoms among HIV-positive MSM undergoing highly active antiretroviral therapy. We found the protective factor associated with sexual difficulties was regular exercise while the risk factor was alcohol consumption. However, the data were collected only from China, and it is still unclear how HRQoL changes after intervention. Conclusion: Routine follow-up for people living with HIV should encompass an investigation into sexual function, emphasizing the need for timely assessment and intervention, particularly in HIV-positive MSM with identified risk factors.

Research on the status and influencing factors of maternal health literacy among postpartum women in urban villages.

AIM: To comprehensively identify the status and influencing factors on maternal health literacy among postpartum women in Guangzhou urban villages. DESIGN: An explanatory sequential mixed-method research was conducted from November 2021 to July 2022. METHODS: The quantitative survey was conducted among postpartum women in Guangzhou urban villages using the convenience sampling principle, and a questionnaire survey was used to reflect the status and influencing factors on maternal health literacy. The qualitative interview conducted purposive sampling based on the survey and semi-structured interviews with women to supplement the non-quantifiable influencing factors. RESULTS: The quantitative survey showed that the maternal health literacy score of 501 women was 193.84 ± 22.23. The quantitative results suggested that ethnicity, education, income, household registration, delivery mode and social support were important influencing factors (p < .15). The qualitative interviews were conducted with 16 women and revealed three themes and eight sub-themes, including demographic factors (ethnicity, education, income, occupation and family history), pregnancy factors (delivery mode and pregnancy complications) and social factors (social support), which influenced maternal health literacy through three routes: women's motivation, access and ability in screening health information. CONCLUSION: Maternal health literacy among postpartum women in urban villages needs to be improved, especially critical health literacy. Maternal and infant workers need to guide women to develop appropriate health information concepts and consider the realistic knowledge needs of women in different socio-cultural and economic backgrounds. They should also construct a comprehensive social support system for women to better improve maternal health literacy. IMPACT: Highlights the positive benefits of maternal health literacy among postpartum women, as preparation for providing accurate and effective maternal and child health education services. PATIENT OR PUBLIC CONTRIBUTION: The information on maternal health literacy in this study was based on an interview with postpartum women in Guangzhou urban villages during the study period.

Light-induced remodeling of phytochrome B enables signal transduction by phytochrome-interacting factor.

Phytochrome B (phyB) and phytochrome-interacting factors (PIFs) constitute a well-established signaling module critical for plants adapting to ambient light. However, mechanisms underlying phyB photoactivation and PIF binding for signal transduction remain elusive. Here, we report the cryo-electron microscopy (cryo-EM) structures of the photoactivated phyB or the constitutively active phyBY276H mutant in complex with PIF6, revealing a similar trimer. The light-induced configuration switch of the chromophore drives a conformational transition of the nearby tongue signature within the phytochrome-specific (PHY) domain of phyB. The resulting α-helical PHY tongue further disrupts the head-to-tail dimer of phyB in the dark-adapted state. These structural remodelings of phyB facilitate the induced-fit recognition of PIF6, consequently stabilizing the N-terminal extension domain and a head-to-head dimer of activated phyB. Interestingly, the phyB dimer exhibits slight asymmetry, resulting in the binding of only one PIF6 molecule. Overall, our findings solve a key question with respect to how light-induced remodeling of phyB enables PIF signaling in phytochrome research.

Pheromone cCF10 inhibits the antibiotic persistence of Enterococcus faecalis by modulating energy metabolism.

Introduction: Bacterial resistance presents a major challenge to both the ecological environment and human well-being, with persistence playing a key role. Multiple studies were recently undertaken to examine the factors influencing the formation of persisters and the underlying process, with a primary focus on Gram-negative bacteria and Staphylococcus aureus (Gram-positive bacteria). Enterococcus faecalis (E. faecalis) is capable of causing a variety of infectious diseases, but there have been few studies of E. faecalis persisters. Previous studies have shown that the sex pheromone cCF10 secreted by E. faecalis induces conjugative plasmid transfer. However, whether the pheromone cCF10 regulates the persistence of E. faecalis has not been investigated. Methods: As a result, we investigated the effect and potential molecular mechanism of pheromone cCF10 in regulating the formation of persisters in E. faecalis OG1RF using a persistent bacteria model. Results and discussion: The metabolically active E. faecalis OG1RF reached a persistence state and temporarily tolerated lethal antibiotic concentrations after 8 h of levofloxacin hydrochloride (20 mg/mL) exposure, exhibiting a persistence rate of 0.109 %. During the growth of E. faecalis OG1RF, biofilm formation was a critical factor contributing to antibiotic persistence, whereas 10 ng/mL cCF10 blocked persister cell formation. Notably, cCF10 mediated the antibiotic persistence of E. faecalis OG1RF via regulating metabolic activity rather than suppressing biofilm formation. The addition of cCF10 stimulated the Opp system and entered bacterial cells, inhibiting (p)ppGpp accumulation, thus maintaining the metabolically active state of bacteria and reducing persister cell generation. These findings offer valuable insights into the formation, as well as the control mechanism of E. faecalis persisters.

Precise hourly personalized embryo transfer significantly improves clinical outcomes in patients with repeated implantation failure.

Purpose: This study investigated whether RNA-Seq-based endometrial receptivity test (rsERT)-which provides precision for the optimal hour of the window of implantation (WOI)-can improve clinical outcomes of frozen embryo transfer (FET) cycles in patients with a history of repeated implantation failure (RIF). Methods: Patients with a history of RIF who received at least one autologous high-quality blastocyst during the subsequent FET cycle were retrospectively enrolled and divided into two groups: rsERT and FET, comprising patients who underwent rsERT-guided pET (n=115) and standard FET without rsERT (n=272), respectively. Results: In the rsERT group, 39.1% (45/115) of patients were receptive. rsERT patients showed a higher probability of achieving both positive human chorionic gonadotropin (63.5% vs. 51.5%, P=0.03) and clinical pregnancy (54.8% vs. 38.6%, P=0.003) rates. In subgroup analysis, rsERT patients with non-receptive results had higher clinical pregnancy rates than patients undergoing FET (58.6% vs. 38.6%, P=0.003). rsERT patients with receptive results guided by rsERT with a precise WOI time had higher, although non-significant, clinical pregnancy rates (48.9% vs. 38.6%, P=0.192) than patients who underwent standard-time FET. Conclusion: Hourly precise rsERT can significantly improve the probability of achieving clinical pregnancy in patients with RIF, especially in those with non-receptive rsERT results.

KGRLFF: Detecting Drug-Drug Interactions Based on Knowledge Graph Representation Learning and Feature Fusion.

Accurate prediction of drug-drug interactions (DDIs) plays an important role in improving the efficiency of drug development and ensuring the safety of combination therapy. Most existing models rely on a single source of information to predict DDIs, and few models can perform tasks on biomedical knowledge graphs. This paper proposes a new hybrid method, namely Knowledge Graph Representation Learning and Feature Fusion (KGRLFF), to fully exploit the information from the biomedical knowledge graph and molecular structure of drugs to better predict DDIs. KGRLFF first uses a Bidirectional Random Walk sampling method based on the PageRank algorithm (BRWP) to obtain higher-order neighborhood information of drugs in the knowledge graph, including neighboring nodes, semantic relations, and higher-order information associated with triple facts. Then, an embedded representation learning model named Knowledge Graph-based Cyclic Recursive Aggregation (KGCRA) is used to learn the embedded representations of drugs by recursively propagating and aggregating messages with drugs as both the source and destination. In addition, the model learns the molecular structures of the drugs to obtain the structured features. Finally, a Feature Representation Fusion Strategy (FRFS) was developed to integrate embedded representations and structured feature representations. Experimental results showed that KGRLFF is feasible for predicting potential DDIs.

Sources of stress and coping strategies among Chinese medical graduate students: a qualitative study.

BACKGROUND: The incidence of mental health problems among medical graduate students is much higher than among students of other disciplines. This can have adverse consequences for the medical students themselves as well as their future patients. This study aims to understand the pressures faced by Chinese medical students and the current status of mental health education. It also propose recommendations for the current situation and prospects for the future. METHOD: The authors conducted in-depth semi-structured interviews with 22 master's students from five medical schools during November 2023. All interview sessions were recorded and transcribed verbatim. The transcriptions were analyzed using the Colaizzi's seven-step method. RESULT: Three main themes were extracted from the students' statements: sources of psychological stress, ways to cope with stress, and perspectives on mental health education. The study showed that current mental health education in China is mostly in the form of printed mental health education manuals and mental health lectures, and there is no active tiered intervention for students at different levels. It is suggested that reforms should be made to shift to a model where the school proactively identifies problems and intervenes based on feedback. CONCLUSION: This study reveals the widespread psychological stress and shortcomings in current education methods. To address these challenges, institutions should develop tailored interventions, including tiered support systems, open dialogue promotion, and resilience training. Future research should focus on evaluating innovative interventions' effectiveness, ultimately fostering a supportive environment that enhances students' success and contributes to a healthier healthcare workforce.

Reduced inhibitory synaptic transmission onto striatopallidal neurons may underlie aging-related motor skill deficits.

Human beings are living longer than ever before and aging is accompanied by an increased incidence of motor deficits, including those associated with the neurodegenerative conditions, Parkinson's disease (PD) and Huntington's disease (HD). However, the biological correlates underlying this epidemiological finding, especially the functional basis at the synapse level, have been elusive. This study reveals that motor skill performance examined via rotarod, beam walking and pole tests is impaired in aged mice. This study, via electrophysiology recordings, further identifies an aging-related reduction in the efficacy of inhibitory synaptic transmission onto dorsolateral striatum (DLS) indirect-pathway medium spiny neurons (iMSNs), i.e., a disinhibition effect on DLS iMSNs. In addition, pharmacologically enhancing the activity of DLS iMSNs by infusing an adenosine A2A receptor (A2AR) agonist, which presumably mimics the disinhibition effect, impairs motor skill performance in young mice, simulating the behavior in aged naïve mice. Conversely, pharmacologically suppressing the activity of DLS iMSNs by infusing an A2AR antagonist, in order to offset the disinhibition effect, restores motor skill performance in aged mice, mimicking the behavior in young naïve mice. In conclusion, this study identifies a functional inhibitory synaptic plasticity in DLS iMSNs that likely contributes to the aging-related motor skill deficits, which would potentially serve as a striatal synaptic basis underlying age being a prominent risk factor for neurodegenerative motor deficits.

The Efficacy and Safety of Roxadustat for the Treatment of Posttransplantation Anemia: A Randomized Study.

Introduction: Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, can stimulate erythropoiesis. Our objective was to evaluate the efficacy and safety of roxadustat for the treatment of posttransplantation anemia (PTA). Methods: A total of 150 adult renal transplant recipients who underwent PTA were randomized to either the experimental group or the control group. During the 12-week randomized phase, the experimental group was randomized to oral iron and roxadustat treatment, and the control group was randomized to oral iron treatment only. The randomized phase was followed by a 12-week extended treatment period in which all participants were prescribed roxadustat treatment according to hemoglobin (Hb) levels. All the participants were followed-up with every 4 weeks. The primary end points were the change in Hb levels and response rate throughout the randomized period. Results: A total of 128 participants completed the randomized treatment period (90 in the experimental group and 38 in the control group). The mean Hb concentration at week 12 was 12.20 g/dl in the experimental group and 11.19 g/dl in the control group. A significantly higher proportion of participants who achieved Hb responses were in the experimental group than in the control group. Differences in serum iron, total iron-binding capacity (TIBC) and transferrin from baseline to week 8 to 12 were significant between the 2 groups. The adverse event profiles were comparable between the 2 groups. Conclusion: Roxadustat increased Hb in adult renal transplant recipients who underwent PTA, with an adverse event profile comparable to that of the control group.

Estimated Pulse Wave Velocity as a Novel Non-Invasive Biomarker for Metabolic Syndrome Among People Living with HIV.

Purpose: This study aims to investigate the relationship between estimated pulse wave velocity (ePWV) and metabolic syndrome (MetS) in people living with HIV (PLWH), proposing a novel and convenient predictor for early detection of MetS in PLWH. Patients and Methods: A total of 485 PLWH were enrolled. These participants were categorized into two groups based on the estimated pulse wave velocity (ePWV) level. Demographic and clinical data were collected to investigate the correlation between ePWV and MetS. Results: The cohort of 485 PLWH was categorized into high-ePWV and low-ePWV groups based on ePWV cutoff value of 10 m/s. We observed significant differences in components of MetS including triglycerides (TG, P < 0.05), HDL cholesterol (HDL-C, P < 0.01), systolic blood pressure (SBP, P < 0.001), diastolic blood pressure (DBP, P < 0.05), and fasting plasma glucose (FPG, P < 0.001) between the two groups. Furthermore, we employed receiver operating characteristic (ROC) curves to demonstrate the effectiveness of ePWV as a predictive indicator for MetS in PLWH (AUC = 0.739, P < 0.001). According to the ROC curve, the optimal cut-off value of ePWV was 7.4 m/s, and its sensitivity and specificity in diagnosing MetS in PLWH were 79.03% and 64.07%, respectively. Although the 7.4 m/s cutoff increased the false positive rate compared to the traditional cutoff, it significantly reduced the rate of missed diagnoses, effectively identifying 79.03% of PLWH with MetS. Conclusion: ePWV is a non-invasive and convenient novel biomarker with predictive capabilities for MetS in PLWH.

The impact of family residence structure on adolescents' non-cognitive abilities: evidence from China.

Purpose: The family residence structure serves as a crucial pathway through which the family environment influences adolescents' development. Methods: Drawing on nationally representative data, this study employs multiple linear regression models and propensity score matching to examine the impact of various family residence structures on adolescents' non-cognitive abilities. Causal identification is achieved through propensity score matching, while robustness is assessed using methods such as augmented inverse probability weighting and placebo tests. Heterogeneity analysis is conducted based on gender and household registration, aiming to explore the mechanisms by which family residence structure affects adolescents' non-cognitive abilities. Results: The findings indicate that compared to two-parent co-residence households, three-generation co-residence families have significantly positive effects on emotional stability, conscientiousness, and agreeableness among adolescents. In contrast, skip-generation coresidence families exhibit significant negative effects on emotional stability and agreeableness in adolescents. Further investigation into the underlying mechanisms reveals that parental involvement and family socioeconomic status within three-generation co-residence families positively influence adolescents' non-cognitive abilities. Conclusion: This study highlights the importance of considering grandparents' role in adolescent growth and advocates for policy recommendations focusing on enhancing non-cognitive abilities in adolescents from skip-generation co-residence families.

Effect of mode of delivery on postpartum weight retention: A systematic review and meta-analysis.

OBJECTIVE: Retention of weight gained over pregnancy increases the risk of long-term obesity and related health concerns. While many risk factors for this postpartum weight retention have been examined, the role of mode of delivery in this relationship remains controversial. We carried out a systematic review and meta-analysis to determine the effect of mode of delivery on postpartum weight retention. METHODS: Ten electronic databases including PubMed, Cochrane Library, EMBASE, Web of Science, MEDLINE, CINAHL, China National Knowledge Infrastructure (CNKI), Wan-Fang database, the VIP database and China Biology Medicine Database (CBM) were searched from inception through November 2022. Review Manager 5.4 was used to pool the study data and calculate effect sizes. For dichotomous data, the odds ratio and 95 % confidence interval were used to report the results. For continuous data, the mean difference (MD) and 95 % confidence interval were used to report the results. The outcomes were the amount of postpartum weight retention and the number or proportion of women who experienced postpartum weight retention. The Newcastle- Ottawa Scale (NOS) and GRADE Guidelines were used to assess the methodological quality of the included studies. FINDINGS: A total of 16 articles were included in the systematic review and 13 articles were included in the meta-analysis. The results showed that the mode of delivery had a significant effect on postpartum weight retention, women who delivered by caesarean section were more likely to experience postpartum weight retention compared to those who delivered vaginally. Sensitivity analysis showed that the results were stable and credible. CONCLUSION: Due to the limitations of this study, the findings need to be treated with caution. And, to better prevent the postpartum weight retention, future practice and research need to further focus on upstream modifiable factors.

Robot-assisted laparoscopic retroperitoneal donor nephrectomy: a safe and efficient improvement.

PURPOSE: Reducing operative injuries is important in living donor nephrectomy. The robot-assisted transperitoneal approach has some advantages than traditional laparoscopic techniques. However, longer operation time and risks of abdominal complications indicate the need for improved techniques. The aim of this study is to present the robot-assisted laparoscopic retroperitoneal donor nephrectomy and evaluate its safety and feasibility. METHODS: This was a retrospective study. From June 2016 to December 2020, 218 living donors underwent robot-assisted laparoscopic retroperitoneal donor nephrectomy. Perioperative data such as operation time, warm ischemia time, length of stay and complications were collected and analyzed. To evaluate the feasibility of this surgical technique, the cumulative summation method was used to construct a learning curve. RESULTS: There were 60 male and 158 female donors aged 36-72 years, with an average age of 53.1 ± 6.8 years. Three patients (1.4%) were converted to open surgery. The mean operation time was 115.4 ± 41.9 min, the warm ischemia time was 206.6 ± 146.7 s, and the length of stay was 4.1 ± 1.4 days. Complications were reported in 22 patients (10.1%), three of whom (1.4%) had Clavien‒Dindo IIIa complications. No ileus occurred. No donors were readmitted. Four patients had delayed graft function. The cumulative summation curve showed that the number needed to reach proficiency was 33. The operation time and warm ischemia time after technical proficiency were 100.4 ± 21.6 min and 142.5 ± 50.7 s, respectively. CONCLUSION: Robot-assisted laparoscopic retroperitoneal donor nephrectomy is a safe and efficient technique that offers advantages of shorter operation time and no abdominal organ interference.

Patients with chronic hepatitis B who have persistently normal alanine aminotransferase or aged < 30 years may exhibit significant histologic damage.

BACKGROUND: The timing of antiviral therapy for chronic hepatitis B (CHB) patients with normal alanine transaminase (ALT) or aged < 30 years is still undetermined. We aimed to elucidate the correlation between liver histology, age, and ALT level in CHB patients and analyze the histological characteristics of the liver among patients with persistently normal ALT or aged < 30 years. METHODS: A retrospective analysis was conducted on 697 treatment-naive CHB patients. Liver biopsies were performed, and significant histological damage was defined as the grade of liver inflammation ≥ G2 and/or fibrosis ≥ S2 based on the Scheuer scoring system. RESULTS: The liver inflammation grades and fibrosis stages correlated positively with age, ALT, AST, GGT levels and negatively with the counts of PLT (all p < 0.050) in HBeAg-positive patients. Higher ALT levels and lower PLT counts were independently associated with significant liver inflammation and fibrosis in both HBeAg-positive and HBeAg-negative patients. Furthermore, among those with persistently normal ALT levels, the incidence of significant liver inflammation and fibrosis were 66.1% and 53.7% in HBeAg-positive groups, and 63.0% and 55.5% in HBeAg-negative groups. Moreover, there was no significant difference in the prevalence of significant liver damage between patients aged < 30 years and those aged ≥ 30 years, in both HBeAg-positive (≥ G2 or ≥ S2: 63.8% vs. 75.8%, p = 0.276) and HBeAg-negative (≥ G2 or ≥ S2: 65.9% vs. 72.5%, p = 0.504) groups, among patients with persistently normal ALT levels. CONCLUSIONS: A considerable proportion of CHB patients with persistently normal ALT, including those below the age of 30 years, exhibited significant histological damage. This highlights the importance of initiating early antiviral therapy for HBV-infected individuals, even in the absence of elevated ALT levels.

The association between fear of progression and medical coping strategies among people living with HIV: a cross-sectional study.

BACKGROUND: Due to the chronic nature of HIV, mental health has become a critical concern in people living with HIV (PLWHIV). However, little knowledge exists about the association between fear of progression (FoP) and medical coping modes (MCMs) in PLWHIV in China. METHODS: A cohort of 303 PLWHIV were consecutively enrolled and their demographic, clinical and psychological information was collected. The Fear of Progression Questionnaire-Short Form (FoP-Q-SF), Social Support Rating Scale (SSRS), Internalized HIV Stigma Scale (IHSS) and MCMs Questionnaire were utilized. RESULTS: Of the participants, 215 PLWHIV were classified into the low-level FoP group, and 88 were grouped into the high-level FoP group based on their FoP-Q-SF scores, according to the criteria for the classification of dysfunctional FoP in cancer patients. The high-level group had a higher proportion of acquired immunodeficiency syndrome (AIDS) stage (P = 0.005), lower education levels (P = 0.027) and lower income levels (P = 0.031). Additionally, the high-level group had lower scores in social support (P < 0.001) and its three dimensions, with total SSRS scores showing a negative correlation with two dimensions of FoP-Q-SF, namely physical health (r2 = 0.0409, P < 0.001) and social family (r2 = 0.0422, P < 0.001). Further, the high-level group had higher scores in four dimensions of internalized HIV stigma, and a positive relationship was found to exist between IHSS scores and FoP-Q-SF scores for physical health (r2 = 0.0960, P < 0.001) and social family (r2 = 0.0719, P < 0.001). Social support (OR = 0.929, P = 0.001), being at the AIDS stage (OR = 3.795, P = 0.001), and internalized HIV stigma (OR = 1.028, P < 0.001) were independent factors for FoP. Furthermore, intended MCMs were evaluated. FoP were positively correlated with avoidance scores (r2 = 0.0886, P < 0.001) and was validated as the only factor for the mode of confrontation (OR = 0.944, P = 0.001) and avoidance (OR = 1.059, P = 0.001) in multivariate analysis. CONCLUSION: The incidence of dysfunctional FoP in our study population was relatively high. High-level FoP was associated with poor social support, high-level internalized HIV stigma and a negative MCM among PLWHIV.

Functional characterization of D-type cyclins involved in cell division in rice.

BACKGROUND: D-type cyclins (CYCD) regulate the cell cycle G1/S transition and are thus closely involved in cell cycle progression. However, little is known about their functions in rice. RESULTS: We identified 14 CYCD genes in the rice genome and confirmed the presence of characteristic cyclin domains in each. The expression of the OsCYCD genes in different tissues was investigated. Most OsCYCD genes were expressed at least in one of the analyzed tissues, with varying degrees of expression. Ten OsCYCD proteins could interact with both retinoblastoma-related protein (RBR) and A-type cyclin-dependent kinases (CDKA) forming holistic complexes, while OsCYCD3;1, OsCYCD6;1, and OsCYCD7;1 bound only one component, and OsCYCD4;2 bound to neither protein. Interestingly, all OsCYCD genes except OsCYCD7;1, were able to induce tobacco pavement cells to re-enter mitosis with different efficiencies. Transgenic rice plants overexpressing OsCYCD2;2, OsCYCD6;1, and OsCYCD7;1 (which induced cell division in tobacco with high-, low-, and zero-efficiency, respectively) were created. Higher levels of cell division were observed in both the stomatal lineage and epidermal cells of the OsCYCD2;2- and OsCYCD6;1-overexpressing plants, with lower levels seen in OsCYCD7;1-overexpressing plants. CONCLUSIONS: The distinct expression patterns and varying effects on the cell cycle suggest different functions for the various OsCYCD proteins. Our findings will enhance understanding of the CYCD family in rice and provide a preliminary foundation for the future functional verification of these genes.

Erzhiwan Ameliorates Restraint Stress- and Monobenzone-Induced Depigmentation in Mice by Inhibiting Macrophage Migration Inhibitory Factor and 8-Hydroxy-2-Deoxyguanosine.

Purpose: Vitiligo is an autoimmune disease that results in the loss of epidermal melanocytes. The treatments for patients with vitiligo remain lacking. Erzhiwan (EZW), a traditional Chinese Medicine composed of Ligustri Lucidi Fructus and Ecliptae Herba, was used to ameliorate depigmentation since ancient China. This study aims to investigate the effect of EZW on vitiligo-related depigmentation. Methods: A vitiligo-related depigmentation mouse model was induced by monobenzone and restraint stress. The experimental depigmentation mice were treated with EZW. Histological observation of skin was conducted. Cutaneous oxidative damage and inflammation were determined. A network pharmacology analysis was carried out. Results: EZW reduced depigmentation score (p<0.01), cutaneous inflammatory infiltration (p<0.01), and CD8α-positive expression (p<0.01), and increased cutaneous melanin content in experimental depigmentation mice. EZW reduced stress reaction in experimental depigmentation mice (p<0.01). EZW inhibited 8-hydroxy-2-deoxyguanosine (8-OHdG)-related DNA oxidative damage in the skin (p<0.05, p<0.01). In addition, EZW reduced cutaneous macrophage migration inhibitory factor (MIF)-CD74-NF-κB signaling (p<0.01). The network pharmacology analysis demonstrated that EZW regulated necroptosis, apoptosis, and FoxO signaling pathways in vitiligo. An in vitro experiment showed that the main ingredient of EZW, specnuezhenide, protected against monobenzone and MIF-induced cell death in HaCaT cells (p<0.01). Conclusion: EZW ameliorates restraint stress- and monobenzone-induced depigmentation via the inhibition of MIF and 8-OHdG signaling. The findings provide a data basis of an utilization of EZW in vitiligo.

Chinese herbal medicine for irinotecan-induced diarrhea: A systematic review and meta-analysis.

INTRODUCTION: Irinotecan is a novel first-line therapy for colorectal cancer, but the toxicity and side effects include diarrhea without satisfactory treatments. Chinese herbal decoction (CHD) is an effective complementary and alternative prevention and therapy for irinotecan induced diarrhea (IID). This systematic review and meta-analysis of randomized controlled trials (RCTs) aims to assess the preventive effect of CHD in the treatment of IID. METHODS: Seven databases (PubMed, COCHRANE, EMBASE, CNKI, VIP, Wanfang, and CBM) were screened for random controlled trials on the prevention and treatment of IID by CHD from January 1980 to May 2022. The Cochrane Collaboration Risk of Bias (ROB 2.0) was applied for bias risk assessment, and the Grading Recommendation Assessment, Development, and Evaluation (GRADE) for quality of evidence. Meta-analysis was conducted with RevMan 5.3 software. In addition, a subgroup analysis was conducted on different grades of diarrhea, the incidence and duration of diarrhea, the selection of specific Chinese herbal medicine decoction, and the incidence of adverse reactions. Risk ratios (RR) and 95% confidence intervals (CIs) were calculated for all data by combining the meta-analysis with fixed or random-effects models based on outcome heterogeneity. RESULTS: Fourteen RCTs involving 1056 participants were included. The study results displayed that the incidence of IID was lower with the use of CHD than the no-treatment group (RR = 0.55, 95% CI = 0.40-0.75, P = 0.0002). CHD in combination with western medicine (WM) was more effective than WM alone for IID (RR = 0.44, 95% CI 0.23-0.84, P = 0.01). This protective effect was more pronounced for severe grade III-V diarrhea (RR = 0.41, 95% CI = 0.26-0.64, P < 0.0001). In the specific Chinese herbal medicine decoction, the Banxia Xie Xin decoction presented better effectiveness (RR = 0.18, 95% CI: 0.05-0.63, P = 0.007) than WM alone. The Huangqin decoction was the most widely studied interventional scheme (n = 5). The relative risk (RR) of the Huangqin decoction was 0.56. No obvious adverse reactions were observed. CONCLUSION: This study demonstrated that CHD has a preventive effect on IID and could be used as a complementary therapy with few side effects. However, additional large-sample, high-quality, randomized, double-blind trials are needed to guide the clinical practice scientifically. SYSTEMATIC REVIEW REGISTRATION: www.crd.york.ac.uk/prospero (NO: CRD42020189506).

Implementation of Thermal-Triggered Binary-Ternary Switchable Memory Performance in Zn/polysulfide/organic Complex-Based Memorizers by Finely Modulating the S62- Relaxation.

Polysulfide-based multilevel memorizers are promising as novel memorizers, in which the occurrence of Sn2- relaxation is key for their multilevel memory. However, the effects of crystal packing and the side group of organic ligands on Sn2- relaxation are still ambiguous. In this work, ionic [Zn(S6)2·Zn2(Bipy)2SO4 (1), Zn(S6)2·Zn(Pmbipy)3 (2)] and neutral [ZnS6(Ombipy) (3), ZnS6(Phen)2 (4)] Zn/polysulfide/organic complexes with different packing modes and structures of organic ligands have been synthesized and were fabricated as memory devices. In both ionic and neutral Zn complexes, the S62- relaxation will be blocked by steric hindrances due to the packing of counter-cations and hydrogen-bond restrictions. Consequently, only the binary memory performances can be seen in FTO/1/Ag, FTO/2/Ag, and FTO/4/Ag, which originate from the more condensed packing of conjugated ligands upon electrical stimulus. Interestingly, FTO/3/Ag illustrates the unique thermally triggered reversible binary-ternary switchable memory performance. In detail, after introducing a methyl group on the 6'-position of bipyridine in ZnS6(Ombipy) (3), the ring-to-chain relaxation of S62- anions at room temperature will be inhibited, but it can happen at a higher temperature of 120 °C, which has been verified by elongated S-S lengths and the strengthened C-H···S hydrogen bond upon heating. The rules drawn in this work will provide a useful guide for the design of stimulus-responsive memorizers that can be applied in special industries such as automobile, oil, and gas industries.

Reduction in the activity of VTA/SNc dopaminergic neurons underlies aging-related decline in novelty seeking.

Curiosity, or novelty seeking, is a fundamental mechanism motivating animals to explore and exploit environments to improve survival, and is also positively associated with cognitive, intrapersonal and interpersonal well-being in humans. However, curiosity declines as humans age, and the decline even positively predicts the extent of cognitive decline in Alzheimer's disease patients. Therefore, determining the underlying mechanism, which is currently unknown, is an urgent task for the present aging society that is growing at an unprecedented rate. This study finds that seeking behaviors for both social and inanimate novelties are compromised in aged mice, suggesting that the aging-related decline in curiosity and novelty-seeking is a biological process. This study further identifies an aging-related reduction in the activity (manifesting as a reduction in spontaneous firing) of dopaminergic neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Finally, this study establishes that this reduction in activity causally underlies the aging-related decline in novelty-seeking behaviors. This study potentially provides an interventional strategy for maintaining high curiosity in the aged population, i.e., compensating for the reduced activity of VTA/SNc dopaminergic neurons, enabling the aged population to cope more smoothly with the present growing aging society, physically, cognitively and socioeconomically.