Suicidal ideation and suicide attempts among students aged 12 to 24 after the lifting of COVID-19 restrictions in China: prevalence and associated factors.

Objective: To investigate the prevalence and associated factors of suicidal ideation and suicide attempts among adolescent and young adults in China from December 14, 2022 to February 28, 2023, when COVID-19 restrictions were lifted. Methods: Students in middle and high schools and colleges and universities in the province of Sichuan, China were asked to complete on-line cross-sectional surveys. Information was collected about sociodemographics, experiences related to the COVID-19 pandemic, suicidal ideation and suicide attempts. Participants also filled out the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 and the Social Support Rate Scale surveys. Factors associated with suicidal ideation or suicide attempts were explored using logistic regression. Results: Of the 82,873 respondents (aged 12 to 24 years), 21,292 (25.7%) reported having thought of suicide at least once in their lifetime, 10,382 (12.5%) reported having thought about suicide within the previous 12 months, and 1,123 (1.4%) reported having attempted it within the previous 12 months. Risk of lifetime suicidal ideation was higher among middle school students than among older students. Risk of suicidal ideation and risk of suicide attempts correlated directly with severity of symptoms of depression and anxiety, and inversely with level of social support. Greater risk of suicidal ideation and suicidal attempts was associated with: being female, living in an urban environment, attending a boarding school, currently being in love, having parents who divorced or remarried, having parents who exhibit non-authoritative parenting behavior, having higher family income, having been COVID-19 infected, having been quarantined for a long time, and being dissatisfied with one's education. Conclusions: Suicidal ideation and suicide attempts remain prevalent among young people in China. The potential associated factors identified in our study may be useful for targeting appropriate psychosocial interventions and developing mental health policies.

Genome sequencing, comparative analysis, and gene expression responses of cytochrome P450 genes in Oryzias curvinotus provide insights into environmental adaptation.

The mangrove fish (Oryzias curvinotus) serves as a model for researching environmental adaptation and sexual development. To further such research, we sequenced and assembled a high-quality 842 Mb reference genome for O. curvinotus. Comparative genomic analysis revealed 891 expanded gene families, including significantly expanded cytochrome P450 (CYP) detoxification genes known to be involved in xenobiotic defense. We identified 69 O. curvinotus CYPs (OcuCYPs) across 18 families and 10 clans using multiple methods. Extensive RNA-seq and qPCR analysis demonstrated diverse spatiotemporal expression patterns of OcuCYPs by developmental stage, tissue type, sex, and pollutant exposure (17ß-estradiol (E2) and testosterone (MT)). Many OcuCYPs exhibited sexual dimorphism in gonads, suggesting reproductive roles in steroidogenesis, while their responsiveness to model toxicants indicates their importance in environmental adaptation through enhanced detoxification. Pathway analysis highlighted expanded CYP genes in arachidonic acid metabolism, drug metabolism, and steroid hormone biosynthesis. This chromosome-level genomic resource provides crucial biological insights to elucidate the functional roles of expanded CYPs in environmental adaptation, sexual development, early life history, and conservation in the anthropogenically impacted mangrove habitats of O. curvinotus. It also enables future ecotoxicology research leveraging O. curvinotus as a pollution sentinel species.

Characterisation of a SapYZU11@ZnFe2O4 biosensor reveals its mechanism for the rapid and sensitive colourimetric detection of viable Staphylococcus aureus in food matrices.

Although bacteriophage-based biosensors hold promise for detecting Staphylococcus aureus in food products in a timely, simple, and sensitive manner, the associated targeting mechanism of the biosensors remains unclear. Herein, a colourimetric biosensor SapYZU11@ZnFe2O4, based on a broad-spectrum S. aureus lytic phage SapYZU11 and a ZnFe2O4 nanozyme, was constructed, and its capacity to detect viable S. aureus in food was evaluated. Characterisation of SapYZU11@ZnFe2O4 revealed its effective immobilisation, outstanding biological activity, and peroxidase-like capability. The peroxidase activity of SapYZU11@ZnFe2O4 significantly decreased after the addition of S. aureus, potentially due to blockage of the nanozyme active sites. Moreover, SapYZU11@ZnFe2O4 can detect S. aureus from various sources and S. aureus isolates that phage SapYZU11 could not lyse. This may be facilitated by the adsorption of the special receptor-binding proteins on the phage tail fibre and wall teichoic acid receptors of S. aureus. Besides, SapYZU11@ZnFe2O4 exhibited remarkable sensitivity and specificity when employing colourimetric techniques to rapidly determine viable S. aureus counts in food samples, with a detection limit of 0.87 × 102 CFU/mL. Thus, SapYZU11@ZnFe2O4 has broad application prospects for the detection of viable S. aureus cells on food substrates.

Characterisation of a colourimetric biosensor SapYZUM13@Mn3O4-NH2 reveals the mechanisms underlying its rapid and sensitive detection of viable Staphylococcus aureus in food.

In this study, a colourimetric biosensor based on bacteriophage SapYZUM13 and an aminated Mn3O4 (Mn3O4-NH2) nanozyme was constructed and evaluated for its ability to detect Staphylococcus aureus in food. The biosensor had a detection time of 20 min, with a detection limit of 2 × 101 CFU/mL and recovery rate of 92.42-106.96%, indicating its high reliability and accuracy in detecting the food pathogen. Mechanistically, SapYZUM13@Mn3O4-NH2 exhibited oxidase-mimicking capability, producing O2•- free radicals which oxidise 3,3',5,5'-tetramethylbenzidine (TMB) to yield blue-coloured oxTMB. In the presence of S. aureus, the oxidase activity decreased remarkably owing to shielding of the nanozyme active sites. Moreover, SapYZUM13@Mn3O4-NH2 could detect viable S. aureus from various sources, likely because of the special receptor-binding proteins of SapYZUM13 adsorbing to the wall teichoic acids on the S. aureus cell surface. Thus, SapYZUM13@Mn3O4-NH2 has broad application prospects for the detection of viable S. aureus in various foods.

Alzheimer's disease and oral manifestations: a bi-directional Mendelian randomization study.

Background: Epidemiological studies have provided evidence suggesting an association between Alzheimer's disease (AD) and various oral manifestations. However, conflicting conclusions have been drawn, and whether a causal association truly exists remains unclear. Methods: In order to investigate the potential causal association between AD and prevalent oral diseases, we conducted a bi-directional two-sample Mendelian randomization analysis based on summary statistics from genome-wide association studies of AD (N = 63,926), as well as mouth ulcer (N = 461,103), oral cavity cancer (N = 4,151), and periodontal disease (N = 527,652). Results: We identified that one standard increase in the risk of AD was causally associated with a reduced risk of oral cavity cancer (OR = 0.76, 95% CI: 0.63-0.92, p = 3.73 × 10-3). In the opposite direction, oral conditions were not causally associated with risk of AD. Conclusion: The present findings contributed to a better understanding of the correlation between AD and oral conditions, specifically oral cavity cancer. These results also identified new avenues for exploring the underlying mechanisms of oral cavity cancer.

A missense GDF5 variant causes brachydactyly type A1 and multiple-synostoses syndrome 2.

Objective: This study aimed to identify the molecular defects and clinical manifestations in a Chinese family with brachydactyly (BD) type A1 (BDA1) and multiple-synostoses syndrome 2 (SYNS2). Methods: A Chinese family with BDA1 and SYNS2 was enrolled in this study. Whole-exome sequencing was used to analyze the gene variants in the proband. The sequences of the candidate pathogenic variant in GDF5 was validated via Sanger sequencing. I-TASSER and PyMOL were used to analyze the functional domains of the corresponding mutant proteins. Results: The family was found to have an autosomal-dominantly inherited combination of BDA1 and SYNS2 caused by the S475N variant in the GDF5 gene. The variant was located within the functional region, and the mutated residue was found to be highly conserved among species. Via bioinformatic analyses, we predicted this variant to be deleterious, which perturb the protein function. The substitution of the negatively charged amino acid S475 with the neutral N475 was predicted to disrupt the formation of salt bridges with Y487 and impair the structure, stability, and function of the protein, consequently, the abnormalities in cartilage and bone development ensue. Conclusions: A single genetic variant (S475N) which disrupt the formation of salt bridges with Y487, in the interface of the antagonist- and receptor-binding sites of GDF5 concurrently causes two pathological mechanisms. This is the first report of this variant, identified in a Chinese family with BDA1 and SYNS2.

Association of a novel frameshift variant and a known deleterious variant in MMR genes with Lynch syndrome in Chinese families.

BACKGROUND: Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome. This condition is characterized by germline variants in DNA mismatch repair (MMR) genes, including MLH1, MSH2, MSH6, and PMS2. In this study, we analyzed the molecular defects and clinical manifestations of two families affected with CRC and proposed appropriate individual preventive strategies for all carriers of the variant. METHODS: We recruited two families diagnosed with CRC and combined their family history and immunohistochemical results to analyze the variants of probands and those of other family members by using whole exome sequencing. Subsequently, gene variants in each family were screened by comparing them with the variants available in the public database. Sanger sequencing was performed to verify the variant sites. An online platform ( https://www.uniprot.org ) was used to analyze the functional domains of mutant proteins. RESULTS: A novel frameshift variant (NM_001281492, c.1129_1130del, p.R377fs) in MSH6 and a known deleterious variant (NM_000249.4:c.1731G > A, p.S577S) in MLH1 were identified in the two families with CRC. Using bioinformatics tools, we noted that the frameshift variant reduced the number of amino acids in the MSH6 protein from 1230 to 383, thereby leading to no MSH6 protein expression. The silent variant caused splicing defects and was strongly associated with LS. 5-Fluorouracil-based adjuvant chemotherapy is not recommended for patients with LS. CONCLUSIONS: The novel frameshift variant (MSH6, c.1129_1130del, p.R377fs) is likely pathogenic to LS, and the variant (MLH1, c.1731G > A, p.S577S) has been further confirmed to be pathogenic to LS. Our findings underscore the significance of genetic testing for LS and recommend that genetic consultation and regular follow-ups be conducted to guide individualized treatment for cancer-afflicted families, especially those with a deficiency in MMR expression.

First Known Human Death After Infection With the Avian Influenza A/H3N8 Virus: Guangdong Province, China, March 2023.

Here, we report on a case of human infection with the H3N8 avian influenza virus. The patient had multiple myeloma and died of severe infection. Genome analysis showed multiple gene mutations and reassortments without mammalian-adaptive mutations. This suggests that avian influenza (A/H3N8) virus infection could be lethal for immunocompromised persons.

The mutual overlapping impact of stress and infection on mental health problems in adolescents and youths during and after COVID-19 pandemic in China.

BACKGROUND: It is unclear about the mutual impact of COVID-19 related psychological stress and infection on mental health of adolescent and youth students. This study aimed to explore the mutual impact of COVID-19 related psychological stress and infection on mental health problems among students. METHODS: This study was conducted from December 14, 2022 to February 28, 2023 in Sichuan, China. Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, PTSD Checklist for DSM-5, Insomnia Severity Index, and Internet Addiction Test were used. Participants were grouped by COVID-19 infection and psychological stress level. The differences among groups were compared, and logistic regression analysis was used to investigate risk factors for depression, anxiety, PTSD and insomnia among groups. RESULTS: Of 90,118 participants, 82,873 (92.0 %) finished the questionnaires and were included in the study. Of 82,873 participants, 33,314 (40.2 %) reported to be infected with COVID-19. Participants had depression symptoms (38.1 %), anxiety symptoms (31.8 %), PTSD (33.9 %), insomnia (34.0 %), and internet addiction (60.3 %). Compared with participants uninfected with low psychological stress level, the risk for symptoms of depression, anxiety, PTSD and insomnia increased by 9.6 %, 12.3 %, 6.6 %, and 12.0 % in participants infected with low psychological stress level (p < 0.001), 106.8 %, 125.9 %, 125.2 %, and 95.7 % in participants uninfected with high psychological stress level (p < 0.001), and 147.3 %, 161.1 %, 158.7 %, and 141.0 % in participants infected with high psychological stress level (p < 0.001). LIMITATION: This study is a cross-sectional design, and no causal associations should be inferred. Infection status was based on self-report of participants with infectious symptoms. CONCLUSION: COVID-19 related psychological stress and infection per se have mutually overlapping impacts on mental health problems among students. Further health policies and psychosocial interventions should be developed to reduce mutually overlapping impact and improve the long-term mental health among students.

A real-world disproportionality analysis of mepolizumab based on the FDA adverse event reporting system.

Background: Mepolizumab has been approved by the FDA for add-on maintenance treatment of severe asthma with an eosinophilic phenotype. Real-world studies on mepolizumab-associated adverse events are limited. The present study aimed to explore mepolizumab-related adverse events based on the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: A disproportionality analysis was performed to assess the safety profile of mepolizumab based on the reports from the FAERS database between October 2015 and December 2022. Demographic information, the time to onset, the safety of long-term mepolizumab exposure as well as safety in pediatric patients were also investigated. Results: A total of 736 significant preferred terms (PTs) were identified among the 13,497 mepolizumab-associated adverse events (AEs) reports collected from the FAERS database. The frequently reported AEs including dyspnea, fatigue, and headache were in line with drug instruction and previous studies. Unexpected significant AEs such as cough, malaise, and chest discomfort were also identified. Most AEs occurred within the first month after mepolizumab initiation. Pneumonia and wheezing were frequently reported in patients with long-term mepolizumab exposure as well as in the pediatric population. Conclusion: Our results were consistent with the observations in previous clinical and real-world studies. New and unexpected AE signals of mepolizumab were also identified. Close attention should be paid to the long-term safety of mepolizumab as well as safety in the pediatric population. Prospective studies are required for optimal use of mepolizumab.

Effects of internet addiction and academic satisfaction on mental health among college students after the lifting of COVID-19 restrictions in China.

Background: Internet addiction (IA) among students, worsened by Coronavirus disease 2019 (COVID-19) pandemic, has become a social problem with the digitalization of school learning and many aspects of daily life. However, few studies on IA have been conducted among students after the lifting of COVID-19 restrictions in China. Method: This large-sample, cross-sectional, online survey was conducted to explore the characteristics of IA and the association among IA, academic satisfaction, and mental health problems from December 14, 2022 to February 28, 2023 in Sichuan, China. All participants (N = 22,605) were students in colleges and universities, recruited via their teachers and professors. Results: Of all the participants, 14,921 (66.0%) participants had IA. Participants with IA were more likely to have depression symptom, anxiety symptom, insomnia, and lifetime suicidal ideation. In addition, participants with severe IA had significantly higher rates of mental health problems (e.g., depression, anxiety, insomnia, and suicidal ideation) than those with mild IA. A significant IA-by-academic satisfactory-interaction on mental health was identified: participants with higher level of IA showed particularly severe symptom of depression, anxiety and insomnia when affected by low satisfactory of academy (p < 0.001). Conclusion: This study reveals that IA has a significantly negative impact on mental health among college students after the lifting of COVID-19 restrictions in China. IA and academic satisfaction have interactive impacts on mental health problems among students. Further educational and health policies and psychosocial interventions should be developed to reduce IA and enhance academic satisfaction for improving students' mental health.

Development and optimization of sustained release triptolide microspheres.

Rheumatoid arthritis is considered a chronic systemic autoimmune disorder that may cause joint destruction. Triptolide, an active component isolated from Tripterygium wilfordii Hook.f., is considered to have promising potential for clinical use in treating rheumatoid arthritis. However, its clinical application has been limited by the narrow therapeutic window, side effects associated with plasma drug fluctuations, low oral bioavailability, and poor patient compliance with the long and frequent dosing regimen. An extended drug release preparation may address these limitations. The aim of this work was therefore to develop, formulate and optimize sustained release triptolide microspheres with poly (lactide-co-glycolide) (PLGA). Triptolide-loaded microspheres were prepared using PLGA as the matrix polymer, dichloromethane as the oil phase, and polyvinyl alcohol (PVA) as the matrix forming emulsifier. An oil-in-water (O/W) emulsion solvent evaporation technique was utilized to prepare the microspheres. Surface response methodology (RSM) coupled with central composite design (CCD) was used to optimize the formulation and a total of twenty formulations were prepared. PVA concentration (X1), PLGA concentration (X2), and theoretical drug content (X3) were selected as independent variables; and drug content (Y1), encapsulation efficiency (Y2), mean diameter (Y3) and the initial release during the first day (Y4) were taken as the response variables. The optimized formulation showed mean diameter of 42.36 µm, drug content of 7.96%, encapsulation efficiency of 80.16% and an initial release of 14.48%. The prepared microspheres exhibited a sustained release profile of triptolide in vitro over 4 weeks, which was wellfitted with a Korsmeyer-Peppas equation. However, the initial drug release (~14%) of triptolide-loaded microspheres was very high and should be specifically investigated in future studies. The results indicate that long-term sustained release microspheres of triptolide can be considered a strategy to overcome the low bioavailability and poor patient compliance with conventional triptolide tablets. The issue of initial burst release and in vivo evaluations should be specifically investigated in the future.

Corrigendum: A heterozygous mutation in NOTCH3 in a Chinese family with CADASIL.

[This corrects the article DOI: 10.3389/fgene.2022.943117.].

Academic performance and mental health among Chinese middle and high school students after the lifting of COVID-19 restrictions.

Background: Although the COVID-19 pandemic has greatly changed the way students studied, it is still unknown about the impact of the COVID-19 pandemic on students' academic performance and mental health. Objective: To explore the academic performance and mental health status of middle and high school students after the lifting of COVID-19 restrictions in China. Methods: An online survey was conducted in Sichuan province, China from Dec 14, 2022 to Feb 28, 2023. All participants were students in middle and high schools, recruited via their teachers. The general information, COVID-19-related information, and academic performance were collected. The Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Internet Addiction Test (IAT) were used to assess the mental health problems. Results: Of 60,268 participants, 36,247 (60.2%) middle and high school students reported that their studies were affected by the COVID-19 pandemic, and 24,864 (41.2%) reported that their academic performance had worsened. The prevalence of depression and anxiety symptoms was 38.4 and 32.7%, respectively. There was a significant association between academic performance change and mental health problems. The logistic regression analysis showed that improved academic performance was a protective factor for depression, and declined academic performance was a risk factor for depression and anxiety. Being COVID-19 infected, family members being infected, with quarantine experience, and with COVID-19-related stigma were risk factors for depression and anxiety. Conclusion: Academic studies and mental health status of middle and high school students in Sichuan, China have been negatively impacted by the COVID-19 pandemic, even after the lifting of COVID-19 restrictions. Students' academic performance, academic concerns, and mental health status should be considered for educational policymakers and institutions to improve students' academic studies and mental well-being.

Identification of a novel CNV at the APC gene in a Chinese family with familial adenomatous polyposis.

Introduction: Familial adenomatous polyposis (FAP) is the second most commonly inherited colorectal cancer (CRC) predisposition caused by germline mutations within the adenomatous polyposis coli (APC) gene. The molecular defects and clinical manifestations of two FAP families were analyzed, and individual prevention strategies suitable for mutation carriers in different families were proposed. Methods and results: The pathogenic gene mutations were identified among the two families using whole-exome sequencing and verified with Sanger sequencing or quantitative polymerase chain reaction (qPCR). One novel (GRCh37:Chr5: 112145676-112174368, del, 28,692 bp) and a known (c.C847T:p.R283X) mutation in the APC gene were pathogenic mutations for FAP, according to the sequencing data and tumorigenesis pattern among the family members. The two mutations led to a premature translational stop signal, synthesizing an absent or disrupted protein product. Conclusion: Our findings expand the known germline mutation spectrum of the APC gene among the Chinese population. This reaffirms the importance of genetic testing in FAP. Genetic consultation and regular follow-ups are necessary for the individualized treatment of cancer-afflicted families with APC expression deficiency. Additional work is required to develop safe and effective chemotherapy and immunotherapy for FAP based on the mutation type.

Identification of an LDLR variant in a Chinese familial hypercholesterolemia and its relation to ROS/NLRP3-Mediated pyroptosis in hepatic cells.

BACKGROUND: Familial hypercholesterolemia (FH) is a common autosomal dominant hereditary disease. Its early diagnosis and intervention significantly improve the patient's quality of life. However, there are few types of research on the FH pathogenic genes in China. METHODS: In this study, we recruited a family diagnosed with FH and used whole exome sequencing (WES) to analyze the proband variants. Intracellular cholesterol level, reactive oxygen species (ROS) level, and the expression of pyroptosis-related genes were detected after overexpression of wild-type or variant LDLR in L02 cells. RESULTS: A heterozygous missense variant predicted to be deleterious to LDLR (c.1879G > A, p.Ala627Thr) was identified in the proband. Mechanistically, intracellular cholesterol level, ROS level, and the expression of pyroptosis-related genes, nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome and components (caspase 1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and NLRP3), gasdermin D (GSDMD), interleukin (IL) -18, IL-1ß was elevated in the variant LDLR group, which was attenuated by inhibition of ROS. CONCLUSIONS: FH is associated with a variant (c.1879G>A, p.Ala627Thr) in the LDLR gene. Regarding the mechanism, the ROS/NLRP3-mediated pyroptosis in hepatic cells may contribute to the pathogenesis of the LDLR variant.

[Nature-effect transformation mechanism of mulberry leaves and silkworm droppings based on chemical composition analysis].

Starting with the relationship between mulberry leaves and silkworm droppings as food and metabolites, this study systematically compared the chemical components, screened out differential components, and quantitatively analyzed the main differential components based on ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and UPLC-Q-TRAP-MS combined with principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). Moreover, the in vitro enzymatic transformation of the representative differential components was studied. The results showed that(1) 95 components were identified from mulberry leaves and silkworm droppings, among which 27 components only exist in mulberry leaves and 8 components in silkworm droppings. The main differential components were flavonoid glycosides and chlorogenic acids.(2) Nineteen components with significant difference were quantitatively analyzed, and the components with significant differences and high content were neochlorogenic acid, chlorogenic acid, and rutin.(3) The crude protease in the mid-gut of silkworm significantly metabolized neochlorogenic acid and chlorogenic acid, which may be an important reason for the efficacy change in mulberry leaves and silkworm droppings. This study lays a scientific foundation for the development, utilization, and quality control of mulberry leaves and silkworm droppings. It provides references for clarifying the possible material basis and mechanism of the pungent-cool and dispersing nature of mulberry leaves transforming into the pungent-warm and dampness-resolving nature of silkworm droppings, and offers a new idea for the study of nature-effect transformation mechanism of traditional Chinese medicine.

[Effect of sulfur fumigation on quality and safety of Lilii Bulbus].

Lilii Bulbus is a commonly used Chinese herbal medicine with both medicinal and edible values, while the market products usually has the problem of sulfur fumigation. Therefore, the quality and safety of Lilii Bulbus products deserve attention. In this study, ultra-high performance liquid chromatography-time of flight-tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was combined with principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) to analyze the differential components of Lilii Bulbus before and after sulfur fumigation. We identified ten markers generated after sulfur fumigation, summarized their mass fragmentation and transformation patterns, and verified the structures of phenylacrylic acid markers of sulfur fumigation. At the same time, the cytotoxicity of the aqueous extracts of Lilii Bulbus before and after sulfur fumigation was evaluated. The results showed that in the concentration range of 0-800 mg·L~(-1), the aqueous extract of Lilii Bulbus after sulfur fumigation had no significant effect on the viability of human liver LO2 cells, human renal proximal tubular HK-2 cells, and rat adrenal pheochromocytoma PC-12 cells. Moreover, the viability of the cells exposed to the aqueous extract of Lilii Bulbus before and after sulfur fumigation showed no significant difference. This study identified phenylacrylic acid and furostanol saponins as markers of sulfur-fumigated Lilii Bulbus for the first time, and made clear that proper sulfur fumigation of Lilii Bulbus would not produce cytotoxicity, providing a theoretical basis for the rapid identification and quality and safety control of sulfur-fumigated Lilii Bulbus.