Follicular fluid-derived exosomal HMOX1 promotes granulosa cell ferroptosis involved in follicular atresia in geese (Anser cygnoides).

The proliferation and death of granulosa cells (GCs) in poultry play a decisive role in follicular fate and egg production. The follicular fluid (FF) contains a variety of nutrients and genetic substances to ensure the communication between follicular cells. Exosomes, as a new intercellular communication, could carry and transport the proteins, RNA, and lipids to react on GCs, which had been found in FF of various domestic animals. Whether exosomes of FF in poultry play a similar role is unclear. In this study, geese, a poultry with low egg production, were chosen, and the effect of FF exosomes on the proliferation and death of GCs was investigated. Firstly, there were not only a large number of healthy small yellow follicles (HSYFs) but also some atresia small yellow follicles (ASYFs) in the egg-laying stage. Also, the GC layers of ASYFs became loose interconnections, inward detachment, and diminished survival rate than that of HSYFs. Besides, compared to HSYFs, the contents of E2, P4, and the mRNA expression levels of ferroptosis-related genes GPX4, FPN1, and FTH1 were significantly decreased, while COX2, NCOA4, VDAC3 mRNA were significantly increased, and the structure of mitochondrial cristae disappeared and the outer membrane broke in the GC layers of ASYFs. Moreover, the ROS, MDA, and oxidation levels in the GC layers of ASYFs were significantly higher than those of HSYFs. All these hinted that ferroptosis might result in a large number of GCs death and involvement in follicle atresia. Secondly, FF exosomes were isolated from HSYFs and ASYFs, respectively, and identified by TEM, NTA, and detection of exosome marker proteins. Also, we found the exosomes were phagocytic by GCs by tracking CM-Dil. Moreover, the addition of ASYF-FF exosomes significantly elevated the MDA content, Fe2+ levels, and the mitochondrial membrane potential (MMP) in GCs, thus significantly inhibiting the proliferation of GCs, which was restored by the ferroptosis inhibitor ferrostatin-1. Thirdly, the proteomic sequencing was performed between FF-derived exosomes of HSYFs and ASYFs. We obtained 1615 differentially expressed proteins, which were mainly enriched in the protein transport and ferroptosis pathways. Among them, HMOX1 was enriched in the ferroptosis pathway based on differential protein-protein interaction network analysis. Finally, the role of HMOX1 in regulating ferroptosis in GCs was further explored. The highly expressed HMOX1 was observed in the exosomes of ASYF-FF than that in HSYF-FF. Overexpression of HMOX1 increased ATG5, LC3II, and NCOA4 expression and reduced the expression of FTH1, GPX4, PCBP2, FPN1 in the ferroptosis pathway, also promoted intracellular Fe2+ accumulation and MDA surge, which drove ferroptosis in GCs. The effects of HMOX1 on ferroptosis could be blocked by its inhibitor Znpp. Taken together, the important protein HMOX1 was identified in FF, which could be delivered to GCs via exosomes, triggering ferroptosis and thus determining the fate of follicles.

Temporin-GHaR Peptide Alleviates LPS-Induced Cognitive Impairment and Microglial Activation by Modulating Endoplasmic Reticulum Stress.

Neuroinflammation is considered an important factor that leads to cognitive impairment. Microglia play a crucial role in neuroinflammation, which leads to cognitive impairment. This study aimed at determining whether temporin-GHaR peptide (GHaR) could improve cognitive function and at uncovering the underlying mechanisms. We found that GHaR treatment alleviated LPS-induced cognitive impairment and inhibited activation of microglia in LPS-induced mice. Furthermore, GHaR inhibited activation of endoplasmic reticulum stress (ERS) and the NF-κB signaling pathway in LPS-induced mice. In vitro, GHaR inhibited M1 polarization of BV2 cells and suppressed TNF-α and IL-6 secretion. Additionally, GHaR neuronal cell viability and apoptosis were induced by LPS-activated microglia-conditioned medium. Moreover, in LPS-induced BV2 cells, GHaR inhibited activation of ERS and the NF-κB signaling pathway. In summary, GHaR improved LPS-induced cognitive and attenuated inflammatory responses via microglial activation reversal. In conclusion, the neuroprotective effects of GHaR were mediated via the ERS signaling pathway.

Bidirectional associations between dietary diversity and depressive symptoms in Chinese adult women: A retrospective cohort study.

OBJECTIVE: This study aimed to examine the bidirectional associations between dietary diversity and clinical depressive symptoms in adult women, and influencing factors of clinical depressive symptoms. METHODS: This longitudinal study included a total of 22,385 participants, each of whom underwent at least two data collections. We used convenience sampling to recruit women from a health management center of a general hospital in southern China from April 2015 to December 2021. They completed an online self-reported health questionnaire, which included demographic characteristics, lifestyle information, the Dietary Diversity Scale (DDS), and the Patient Health Questionnaire-9. RESULTS: New-onset depressive symptoms and low dietary diversity were observed in this study among 1285 and 3223 participants, respectively. Negative associations were observed between baseline low dietary diversity and new-onset depressive symptoms (P < 0.05) and between baseline depressive symptoms and low dietary diversity (P < 0.001). Cross-lagged panel analysis indicated that dietary diversity negatively and prospectively predicted depressive symptoms, but vice versa (P < 0.05). Strong evidence of a nonlinear association between DDS scores and incident depressive symptoms was found (P nonlinear < 0.05) regardless of whether the variables were adjusted. Besides, age, menarche age, physical activity, sleep duration, longer sedentary behavior and other lifestyle factors were influencing factors of depressive symptoms (P < 0.05). CONCLUSIONS: The present study identified bidirectional associations between dietary diversity and depressive symptoms, and the associations were found to have a non-linear pattern. Adherence to dietary diversity and a healthy lifestyle could be effective non-pharmacological preventive measures to reduce the incidence of depressive symptoms.

Protein-enriched and anti-inflammatory dietary patterns, healthy lifestyle index and depressive symptoms: A cross-sectional study of 287,945 adults in China.

OBJECTIVES: Depressive symptoms have a considerable negative impact on mental health. This study aimed to understand the relationship between the protein-enriched and anti-inflammatory dietary index scores, modified healthy lifestyle index scores (Modified HLIS), and depressive symptoms. METHODS: This study used convenience sampling to conduct a single-center cross-sectional survey. From January 1, 2015 to December 31, 2020, a total of 287,945 Chinese adults from a health management center of a general hospital completed an online self-reported health questionnaire, which included demographic characteristics, the Dietary Diversity Scale, the Modified Healthy Lifestyle Index Scores and the Patient Health Questionnaire-9. RESULTS: The higher anti-inflammatory dietary index scores (POR = 0.87; 95 % CI: 0.86-0.87; p < 0.001), moderate modified healthy lifestyle index scores (POR = 0.76; 95 % CI: 0.75-0.78; p < 0.001) and sufficient modified healthy lifestyle index scores (POR = 0.53; 95 % CI: 0.52-0.54; p < 0.001) were negatively associated with depressive symptoms, while the higher protein-enriched dietary index scores (POR = 1.01; 95 % CI: 1.01-1.02; p < 0.001) was positively correlated with depressive symptoms. CONCLUSIONS: This study demonstrated that protein-enriched and anti-inflammatory dietary index scores, and multiple healthy lifestyles are associated depressive symptoms in adults.

Influence of metabolic syndrome and lifestyle factors on thyroid nodules in Chinese adult men: a cross-sectional study.

Introduction: Given the high prevalence of thyroid nodules and the potential for malignancy, it is imperative to understand the various factors that contribute to their development. This study aimed to explore the relationship between metabolic syndrome, lifestyle, and thyroid nodules in adult men in southern China. Methods: This study enrolled a total of 183,990 subjects at a medical examination center in a general hospital in southern China between January 1, 2015, and December 31, 2020. Multivariate logistic regression analysis was utilized to evaluate the relationship between metabolic syndrome, lifestyle factors, and thyroid nodules. Furthermore, structural equation modeling elucidated the intricate relationships among these variables. Results: The prevalence of thyroid nodules among Chinese adult males was 14.9%. Several factors were identified as risk factors for thyroid nodules, including advanced age, irregular meal time, smoking or quitting smoking, quitting drinking, heavy manual labor, hypertension, diabetes, dyslipidemia and centripetal obesity, and those belonging to ethnic minorities and drinking alcohol were found to be protective factors against thyroid nodules. Structural equation modeling highlighted metabolic syndrome's mediating role amidst lifestyle influences on thyroid nodules. Conclusion: The prevalence of thyroid nodules in Chinese adult males is relatively moderate to low. The factors identified in this study can help clinicians identify high-risk patients and develop targeted screening strategies for the timely detection of thyroid nodules. However, further mechanistic research and longitudinal studies are necessary to explore the underlying causes and establish causal relationships.

Effects of rational emotive behavior therapy on alexithymia, anxiety, depression and sleep quality of older people in nursing homes: a quasi-experimental study.

BACKGROUND: Alexithymia, a subclinical cognitive-affective impairment, is prevalent in older people and increases the risk of mental disorders. There is a vast alexithymia treatment gap, with majority of older people in nursing homes lacking access to adequate mental health care. The study aimed to evaluate the effects of rational emotive behavior therapy (REBT) on alexithymia, anxiety, depression and sleep quality of older people in nursing homes. METHODS: This quasi-experimental study was conducted with two groups (the control group and intervention) from March to November 2021. This study enrolled 86 participants, two of whom were lost to follow-up; 42 received usual care (control group) and 42 received REBT based on usual care (intervention group) in nursing homes. The older people in both groups were evaluated at baseline (T0), within one-week post-intervention (T1), and at 3-month follow-up (T3). Generalized estimating equations were used by SPSS version 26 to assess the differential change in the outcomes between the two groups. RESULTS: The intervention group shows significantly greater improvement in alexithymia than the control group at both T1 (ß = -8.167, 95%CI= -10.965, -5.368, P < 0.001) and T2 (ß=-4.119, 95%CI= -7.171, -1.067, P = 0.008). The two groups showed significant differences at both T1 and T2 in both difficulty identifying feelings and difficulty describing feelings. Compared to the control group, the intervention group shows a significant improvement in sleep quality at T2 (ß = -2.048, 95%CI=-4.004, -0.091, P = 0.040). The two groups showed significant differences at both T1 and T2 in both sleep disturbance and daytime dysfunction. For depression and anxiety, no significant differences were found between the intervention and control groups. CONCLUSIONS: REBT showed to be an effective method for improving alexithymia and sleep quality of older people in nursing homes. However, it failed to significantly alleviate anxiety and depression at least in a short-term trial. Refining this intervention may have a broader, more substantial impact on future research.

Construction and Validation of a Reliable Disulfidptosis-Related LncRNAs Signature of the Subtype, Prognostic, and Immune Landscape in Colon Cancer.

Disulfidptosis, a novel form of regulated cell death (RCD) associated with metabolism, represents a promising intervention target in cancer therapy. While abnormal lncRNA expression is associated with colon cancer development, the prognostic potential and biological characteristics of disulfidptosis-related lncRNAs (DRLs) remain unclear. Consequently, the research aimed to discover a novel indication of DRLs with significant prognostic implications, and to investigate their possible molecular role in the advancement of colon cancer. Here, we acquired RNA-seq data, pertinent clinical data, and genomic mutations of colon adenocarcinoma (COAD) from the TCGA database, and then DRLs were determined through Pearson correlation analysis. A total of 434 COAD patients were divided in to three subgroups through clustering analysis based on DRLs. By utilizing univariate Cox regression, the least absolute shrinkage and selection operator (LASSO) algorithm, and multivariate Cox regression analysis, we ultimately created a prognostic model consisting of four DRLs (AC007728.3, AP003555.1, ATP2B1.AS1, and NSMCE1.DT), and an external database was used to validate the prognostic features of the risk model. According to the Kaplan-Meier curve analysis, patients in the low-risk group exhibited a considerably superior survival time in comparison to those in the high-risk group. Enrichment analysis revealed a significant association between metabolic processes and the genes that were differentially expressed in the high- and low-risk groups. Additionally, significant differences in the tumor immune microenvironment landscape were observed, specifically pertaining to immune cells, function, and checkpoints. High-risk patients exhibited a low likelihood of immune evasion, as indicated by the Tumor Immune Dysfunction and Exclusion (TIDE) analysis. Patients who exhibit both a high risk and high Tumor Mutational Burden (TMB) experience the least amount of time for survival, whereas those belonging to the low-risk and low-TMB category demonstrate the most favorable prognosis. In addition, the risk groups determined by the 4-DRLs signature displayed distinct drug sensitivities. Finally, we confirmed the levels of expression for four DRLs through rt-qPCR in both tissue samples from colon cancer patients and cell lines. Taken together, the first 4-DRLs-based signature we proposed may serve for a hopeful instrument for forecasting the prognosis, immune landscape, and therapeutic responses in colon cancer patients, thereby facilitating optimal clinical decision-making.

Assessment on compatibility and safety of labels for pharmaceutical packaging.

Although the secondary packing materials do not directly contact the finished drug products, compound migration may still happen between them. To ensure drug quality and safety, extractables and leachables of the packing materials should be analyzed. In this study, 2,6-di-tert-butyl-4-methylphenol (BHT) was first found in the labels for pharmaceutical packaging. For the identification of the compound, a strategy combining high performance liquid chromatography (HPLC), ultra-performance liquid chromatography-quadrupole time-of-flight mass (UPLC-Q-TOF-MS) and nuclear magnetic resonance (NMR) spectroscopy was utilized. Afterwards, a effective and sensitive HPLC method for quantification of BHT was developed and validated. Finally, a toxicological risk assessment of BHT was performed to ensure the safety of drugs.

Dry-Transferable Photoresist Enabled Reliable Conformal Patterning for Ultrathin Flexible Electronics.

Photolithographic techniques, which are widely used in the silicon-based semiconductor industry, enable the manufacture of high-yield and high-resolution features at the micrometer and nanometer scales. However, conventional photolithographic processes cannot accommodate the micro/nanofabrication of flexible and stretchable electronics. In this study, a microfabrication approach that uses a synthesized, environmentally friendly, and dry-transferable photoresist to enable the reliable conformal manufacturing of thin-film electronics is reported, which is also compatible with the existing cleanroom processes. Photoresists with high-resolution, high-density, and multiscale patterns can be transferred onto various substrates in a defect-free and conformal-contact manner, thus enabling multiple wafer reuses. Theoretical studies are conducted to investigate the damage-free peel-off mechanism of the proposed approach. The in situ fabrication of various electrical components, including ultralight and ultrathin biopotential electrodes, has been demonstrated, which offer lower interfacial impedance, durability, and stability, and the components are applied to collect electromyography signals with superior signal-to-noise ratio (SNR) and quality. Additionally, an exemplary demonstration of a human-machine interface indicates the potential of these electrodes in many emerging applications, including healthcare, sensing, and artificial intelligence.

The moderating role of physical activity on the relationship between work intensity and depressive symptoms among the employees.

Our aim was to examine the associations between work intensity and depressive symptoms among the working population, as well as to identify the impact of physical activity (PA) on these relationships. Spearman correlation analysis was conducted to analyze the correlations among work intensity, PA, and depressive symptoms. Working hours and working days were positively correlated with depressive symptoms (r = 0.108, 0.063; all p values were <0.001). Regular PA, exercise time, exercise frequency, and exercise years were negatively correlated with depressive symptoms (r = -0.121, -0.124, -0.152, -0.149; all p values were <0.001) and working days (r = -0.066, -0.050, -0.069, -0.044; all p values were <0.001), working hours (r = -0.113. -0.106, -0.161, -0.123; all p values were <0.001). Working days was positively correlated with working hours (r = 0.512, p < 0.001). Different levels of PA alleviated the effect of working hours or working days on depressive symptoms. Working hours seemed to be more correlated with depressive symptoms than working days. The results suggest that PA at any level could buffer against the effects of work intensity and might prove a helpful strategy for improving mental health issues among employees.

Additional health education and nutrition management cause more weight loss than concurrent training in overweight young females.

OBJECTIVE: This study aimed to compare the effect of concurrent training and the addition of health education and nutrition management on body composition and health-related outcomes. METHODS: Twenty-four healthy overweight females (20.42 ± 1.02 years, body mass index [BMI] 25.83 ± 3.63 kg∙m-2) were assigned to a concurrent training group (Exe, n = 12) or a concurrent training and health education group (Exe + Edu, n = 12). Both groups completed 8 weeks of concurrent training (6 days/week), whereas the Exe + Edu participants received additional health education and controlled daily energy intake within the basal metabolic rate. Body composition, serum glucose, lipids and related hormones were measured before and after intervention. RESULTS: After intervention, the Exe group lost 2.47 kg (±2.46) of body mass, 2.44 kg (±1.71) of total fat mass (FM), corresponding to a body fat percentage (BF%) of 2.25%. Losses of body mass, total FM and BF% in the Exe + Edu group were -5.19 ± 1.87 kg, -4.42 ± 1.83 kg and -4.33 ± 2.39%, respectively. The Exe + Edu participants had significantly greater reductions of body mass, total FM, and trunk and leg FM relative to the Exe participants (p < 0.05). Serum glucose, lipids, insulin and progesterone levels were improved in both groups without group difference. CONCLUSION: Concurrent training is an effective short-term training strategy for reducing FM and improving fasting glucose, blood lipids and related hormones. Furthermore, the combination of additional health education can achieve greater effects on weight loss and the reduction of total and regional FM, which may be a better obesity treatment method.

Dietary diversity, physical activity and depressive symptoms among middle-aged women: A cross-sectional study of 48,637 women in China.

OBJECTIVE: Depression is the leading cause of mental health-related disease burden. This study aimed to investigate the relationship among dietary diversity, physical activity and depressive symptoms in middle-aged women. METHOD: Based on the WHO guidelines on physical activity, subjects who meet moderate-intensity aerobic physical exercise of 150-300 min per week were qualified or otherwise unqualified. The dietary diversity scores (DDS) were developed according to the balanced diet pagoda and assessed the consumption of nine food groups. The total scores ranged from 0 to 9 and could divide into three levels: insufficient [DDS-1] (score of 1-5), moderate [DDS-2] (score of 6-7), and sufficient [DDS-3] (score of 8-9). RESULTS: An age at menarche ≥12 years old (OR = 0.94; 95 % CI: 0.89-1.00; p < 0.05), a higher dietary diversity score [DDS-3] (OR = 0.59; 95 % CI: 0.55-0.63; p < 0.001), drinking coffee (OR = 0.88; 95 % CI: 0.84-0.92; p < 0.001), and qualified physical activity (OR = 0.69; 95 % CI: 0.66-0.72; p < 0.001) were protective factors for depressive symptoms, while an age at first birth ≤20 years old (OR = 1.23; 95 % CI: 1.12-1.36; p < 0.001) or ≥30 years old (OR = 1.18; 95 % CI: 1.11-1.26; p < 0.001), eating late-night snacks (OR = 1.44; 95 % CI: 1.36-1.52; p < 0.001), drinking sugar-sweetened beverages (OR = 1.15; 95 % CI: 1.06-1.24; p < 0.001), and overeating (OR = 2.30; 95 % CI: 2.069-2.56; p < 0.001) were risk factors. CONCLUSION: This study suggested that dietary diversity and physical activity are associated with depressive symptoms in middle-aged women. To improve dietary diversity, attention should be given to dietary patterns and dietary habits, instead of simply increasing the amount of food.

The TRIM25 Gene in Ducks: Cloning, Characterization and Antiviral Immune Response.

TRIM25, as a significant member of the TRIM family, has been frequently demonstrated in regulating the host's antiviral response by activating innate immunity. Ducks are often asymptomatic carriers of influenza A viruses, but the beneficial roles of TRIM25 in modulating the immune response remain largely unknown in ducks. In this study, we characterized the TRIM25, which contains a 16 bp 5'-UTR, a 279 bp 3'-UTR and a 2052 bp ORF that encodes 683 amino acid residues. In addition, we found that duTRIM25 transcripts were widely expressed in the 10 tissues tested, with higher expression levels in the kidney, liver, muscle and spleen and lower expression levels in the duodenum and blood. In addition, the six kinds of virus- or bacteria-mimicking stimuli were transfected into DEFs, and duTRIM25 was induced significantly with 5'ppp dsRNA stimulation. Furthermore, overexpression of duTRIM25 followed by treatment with 5'ppp dsRNA resulted in an increase in IFN-ß. The SPRY domain of duTRIM25 contributed to promoting IFN-ß activity in DEFs challenged with 5'ppp dsRNA. Taken together, our findings suggest that duck TRIM25 can induce the production of IFN-ß against double-stranded RNA virus stimuli and that the SPRY domain of duTRIM25 was critical for the infection.

The prevalence of thyroid nodules and its factors among Chinese adult women: A cross-sectional study.

Objective: To determine the prevalence of thyroid nodules in Chinese adult women. To analyze the relationships between lifestyle, metabolic syndrome and thyroid nodules. Methods: We conducted a retrospective cross-sectional study in the tertiary hospital from 2017 to 2019. Included participants underwent thyroid color Doppler ultrasonography, lipids examination, and dietary evaluation. Results: Totally 2,784 participants were included, and 933 participants were found to have thyroid nodule(s) by B-ultrasound. The prevalence of thyroid nodules was 33.3%. Women in 50-59 years (OR: 1.746, 95% CI [1.356-2.249]), older than 60 (2.147 [1.540-2.993]) and occupations with mainly manual work (1.780 [1.367-2.317]) were risk factors for thyroid nodules, while moderate dietary diversity (0.624 [0.476-0.817]) and normal triglycerides level (0.739 [0.604-0.905]) were protective factors. Conclusion: Women over 50 and those whose jobs are mainly manual should enhance screening, follow-up and health management of thyroid nodules. Higher dietary diversity is protective measures against thyroid nodules for adult women and should consider dietary balance and the food varieties, not just increased quantities.

Factors to predict the knowledge, attitude and practice of nursing interruptions among nurses: A nationwide cross-sectional survey.

AIM: To identify the knowledge, attitude and practice of nursing interruptions and related factors among nurses in China. BACKGROUND: Nursing interruptions are extremely common and have introduced major security risks and harm to hospitalized patients. However, nursing interruptions' factors are not well known. DESIGN: A nationwide cross-sectional descriptive survey. METHODS: A multistratified random sampling method was used to obtain nurses from five provinces in China. We collected data by online questionnaires (the Knowledge, Attitude and Practice Questionnaire of Nursing Interruptions, the Chinese Revised Safety Attitude Questionnaire and the Coping Adaptation Processing Scale). We used the Mann-Whitney test, the Kruskal-Wallis test, Spearman's linear correlation analysis and multiple linear stepwise regression to analyze the data. A STROBE checklist was used to report the results. RESULTS: Of the 14500 questionnaires distributed, 14302 (98.6 %) were returned. The mean score was 79.69 (SD 17.73) and the level was medium. Having attended nursing interruptions training and attended nursing safety training, safety attitude, coping ability and position were positive factors, while age and marital status were negative factors (F=1068.226, p < 0.001, R2 =0.374, adjusted R2 =0.373). CONCLUSIONS: Chinese nurses expressed a moderate level of knowledge, attitude and practice of nursing interruptions. Safety attitude, having attended nursing interruptions training, coping ability, having attended nursing safety training, position, age and marital status were predictors. RELEVANCE TO CLINICAL PRACTICE: Nursing managers should pay attention to the influencing factors of clinical nurses' knowledge, attitude and practice of nursing interruptions and take effective individualized training for clinical nurses with different ages, positions and marital status to improve their coping ability, so as to ensure nursing safety and improve nursing quality.

Integrated Analysis of Gene Expression and Methylation Data to Identify Potential Biomarkers Related to Atherosclerosis Onset.

Atherosclerosis is a kind of chronic inflammatory cardiovascular disease. Epigenetic regulation plays a crucial role in atherosclerosis. Our study was aimed at finding potential biomarkers associated with the occurrence of atherosclerosis. Two datasets were downloaded from the Gene Expression Omnibus (GEO) database. The epigenome-wide association study (EWAS) analysis was performed on methylation data using CpGassoc package. The differential expression analysis was conducted on mRNA data using limma package. The GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) functional enrichment was done in clusterProfiler package. Finally, the logistic regression model was constructed using generalized linear model (glm) function. Between atherosclerotic vs. nonatherosclerotic samples, totally 4980 cytosine-phosphate-guanine (CpG) sites (annotated to 2860 genes) and 132 differentially expressed genes (DEGs) related to atherosclerosis were identified. The annotated 2860 genes and 132 DEGs were significantly enriched in 9 and 4 KEGG pathways and 289 and 132 GO terms, respectively. After cross-analysis, 6 crucial CpG sites were screened to build the model, including cg01187920, cg03422911, cg08018825, cg10967350, cg14473924, and cg25313204. The diagnostic model could reliably separate the atherosclerosis samples from nonatherosclerotic samples. In conclusion, the 6 CpG sites are probably potential diagnostic biomarkers for atherosclerosis, including cg01187920, cg03422911, cg08018825, cg10967350, cg14473924, and cg25313204.

Neonatal congenital leukemia caused by several missense mutations and AFF1-KMT2A fusion: A case report.

Neonatal leukemia, a congenital form of leukemia, is a rare and fatal disease occurring in the neonatal period. Its etiology and pathogenesis have remained to be fully elucidated and the clinical manifestations differ due to age variability. Acute myeloid leukemia (AML) occurring after birth indicates genetic abnormalities and possibly intrauterine exposure to radiation, drugs or other toxins. The present report described the case of a premature neonate without phenotypic signs of Down syndrome, but with an elevated white blood cell count, mainly pertaining to the monocytes of peripheral blood. At 31 weeks of gestation, delivery by Caesarean section was performed due to fetal distress; however, the infant died three days after birth. Further laboratory examination indicated pediatric myeloid leukemia. The present case report described a case of fetal AML. According to the results of peripheral blood smear and targeted-panel sequencing, 5 missense mutations with clinical significance and a novel AFF1-KMT2A fusion gene were detected, which may be the main causes of AML and death.

Dual-Directional Regulation of Belamcanda chinensis Extract on Ovalbumin-Induced Asthma in Guinea Pigs of Different Sexes Based on Serum Metabolomics.

To explore the potential biomarkers and metabolic pathways underlying the anti-asthma effects of Belamcanda chinensis extract, this study established an ovalbumin-induced allergic bronchial asthma model in guinea pigs. Sixty guinea pigs were randomly divided into the blank control group, model control group, Belamcanda chinensis extract groups (0.8 g/kg, 1.2 g/kg, 1.6 g/kg, respectively), and dexamethasone acetate tablet group (0.5 mg/kg). Starting on the 22nd day, the drugs were administered by gavage for seven consecutive days. Serum and bronchoalveolar lavage fluid (BALF) were collected. The levels of IL-4 and IgE in the serum and IFN-γ and TNF-α in the BALF were detected by ELISA. UPLC-MS was combined with multivariate statistical analyses, including partial least squares discriminant analysis (PLS-DA), and differential metabolites between groups were identified. Metabolic pathway analysis was performed by querying the KEGG (Kyoto Encyclopedia of Genes and Genomes) online database. Female and male guinea pigs were analyzed. The results showed that compared with the model group, the IgE and IL-4 serum levels were significantly decreased in the 1.6 g/kg group, and the IFN-γ level in the BALF was significantly increased. The TNF-α level was significantly decreased in the 1.2 g/kg and 1.6 g/kg groups. There were 39 common differential metabolites among females and males, and 37 differential metabolites showed opposite regulatory trends in the serum of guinea pigs with asthma and after treatment, mainly involving 17 metabolic pathways, such as pantothenate and CoA biosynthesis, the arachidonic acid mechanism, and glycerophospholipid metabolism. Belamcanda chinensis extract improved OVA-induced asthma, as determined based on immune mechanisms, inflammation, nerve metabolism, and energy metabolism. The serum levels of metabolites produced by the model animals exhibited distinct sex-specific differences, and the treatment effect of Belamcanda chinensis extract also showed sex-specific differences and bidirectional regulation.

An ultrapotent RBD-targeted biparatopic nanobody neutralizes broad SARS-CoV-2 variants.

The wide transmission and host adaptation of SARS-CoV-2 have led to the rapid accumulation of mutations, posing significant challenges to the effectiveness of vaccines and therapeutic antibodies. Although several neutralizing antibodies were authorized for emergency clinical use, convalescent patients derived natural antibodies are vulnerable to SARS-CoV-2 Spike mutation. Here, we describe the screen of a panel of SARS-CoV-2 receptor-binding domain (RBD) targeted nanobodies (Nbs) from a synthetic library and the design of a biparatopic Nb, named Nb1-Nb2, with tight affinity and super-wide neutralization breadth against multiple SARS-CoV-2 variants of concern. Deep-mutational scanning experiments identify the potential binding epitopes of the Nbs on the RBD and demonstrate that biparatopic Nb1-Nb2 has a strong escape-resistant feature against more than 60 tested RBD amino acid substitutions. Using pseudovirion-based and trans-complementation SARS-CoV-2 tools, we determine that the Nb1-Nb2 broadly neutralizes multiple SARS-CoV-2 variants at sub-nanomolar levels, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Lambda (C.37), Kappa (B.1.617.1), and Mu (B.1.621). Furthermore, a heavy-chain antibody is constructed by fusing the human IgG1 Fc to Nb1-Nb2 (designated as Nb1-Nb2-Fc) to improve its neutralization potency, yield, stability, and potential half-life extension. For the new Omicron variant (B.1.1.529) that harbors unprecedented multiple RBD mutations, Nb1-Nb2-Fc keeps a firm affinity (KD < 1.0 × 10-12 M) and strong neutralizing activity (IC50 = 1.46 nM for authentic Omicron virus). Together, we developed a tetravalent biparatopic human heavy-chain antibody with ultrapotent and broad-spectrum SARS-CoV-2 neutralization activity which highlights the potential clinical applications.

α-Conotoxin TxIB Improved Behavioral Abnormality and Changed Gene Expression in Zebrafish (Danio rerio) Induced by Alcohol Withdrawal.

Background and Purpose: Alcohol use disorder (AUD) is a serious public health issue and affects the lives of numerous people. Previous studies have shown a link between nicotinic acetylcholine receptors (nAChR) and alcohol addiction. However, the role of α6ß2* nAChR in alcohol addiction remains obscure, and whether α6ß2* nAChR can be used as a potential drug target for alcohol withdrawal need to be studied. Methods: Zebrafish (Danio rerio) were exposed to 0.2% alcohol for 14 days followed by 7 days of repeated withdrawal and then retro-orbitally injected with α-conotoxin TxIB (a selective α6ß2* nAChR antagonist). Open Field Test was applied to characterize zebrafish behavior parameters. The monoamine neurotransmitter amounts and their mRNA expression in the zebrafish brain were identified using ELISA and quantitative real-time PCR (RT-PCR). RNA-sequencing (RNA-seq) and subsequent bioinformatics analysis were employed to explore the potential network regulation of TxIB after alcohol withdrawal. Results: The max speed in the center area of the Open Field Test was significantly higher in the withdrawal group whereas TxIB injection corrected this abnormality. The amount and mRNA expression of monoamine neurotransmitters did not change significantly after alcohol withdrawal and TxIB administration. RNA sequencing of zebrafish brain indicated a total of 657 genes showed aberrant expression and among which 225 were reversed after TxIB injection. These reversed genes were significantly enriched in the calcium ion binding pathway and the gene expression profile was further validated by RT-PCR. Conclusion: Our finding suggests α-conotoxin TxIB improved behavioral abnormality induced by alcohol-withdrawal, and changed gene expression mainly in the calcium signaling pathway. Therefore, α-conotoxin TxIB is expected to become a potential therapeutic agent for alcohol withdrawal.