SARS-CoV-2 evolution from the BA.2.86 to JN.1 variants: unexpected consequences.

SARS-CoV-2 is continuously evolving. The Omicron subvariant BA.2.86, with >30 mutations in its spike (S) protein compared with its predecessor strain BA.2, was expected to quickly become predominant worldwide, but this has not happened. Instead, its descendant strain, JN.1, with just one additional mutation, has become the predominant SARS-CoV-2 subvariant. Here, we offer a possible explanation for these unexpected consequences.

A pan-sarbecovirus vaccine based on RBD of SARS-CoV-2 original strain elicits potent neutralizing antibodies against XBB in non-human primates.

The recently emerged Omicron subvariants XBB and BQ.1.1 have presented striking immune evasion against most monoclonal neutralizing antibodies and convalescent plasma. Therefore, it is essential to develop broad-spectrum COVID-19 vaccines to combat current and future emerging variants. Here, we found that the human IgG Fc-conjugated RBD of the original SARS-CoV-2 strain (WA1) plus a novel STING agonist-based adjuvant CF501 (CF501/RBD-Fc) could induce highly potent and durable broad-neutralizing antibody (bnAb) responses against Omicron subvariants, including BQ.1.1 and XBB in rhesus macaques with NT50s ranging from 2,118 to 61,742 after three doses. A decline of 0.9- to 4.7-fold was observed in the neutralization activity of sera in the CF501/RBD-Fc group against BA.2.2, BA.2.9, BA.5, BA.2.75, and BF.7 relative to D614G after three doses, while a significant decline of NT50 against BQ.1.1 (26.9-fold) and XBB (22.5-fold) relative to D614G. However, the bnAbs were still effective in neutralizing BQ.1.1 and XBB infection. These results suggest that the conservative but nondominant epitopes in RBD could be stimulated by CF501 to generate bnAbs, providing a proof-of-concept for using "nonchangeable against changeables" strategy to develop pan-sarbecovirus vaccines against sarbecoviruses, including SARS-CoV-2 and its variants.

Immunotherapy rechallenge of advanced lung adenocarcinoma with cadonilimab (PD-1/CTLA-4 Bi-specific antibody): a case report.

Lung adenocarcinoma (ADC) is a common pulmonary malignant disease with poor prognosis. Immunotherapeutic strategies are the current cornerstone of first-line therapy in driver-negative advanced lung ADC, but there is no treatment standard once the disease has progressed after the first-line application of immune checkpoint inhibitors (ICIs). Clinically, immunotherapy rechallenges are being attempted. However, it is undeniable that there are still great limitations to rechallenging patients with single- or double-ICI immunotherapy though immunotherapy rechallenges can bring new benefits. Cadonilimab (AK104), a unique bi-specific antibody targeting PD-1/CTLA-4, has similar biological activity but lower toxicity than the combination of CTLA-4 and PD-1 antibodies. Herein, we report a case of advanced lung ADC rechallenged with cadonilimab as a posterior-line therapy. The condition of the patient was maintained at stable disease for 6 months. This might provide a new idea and choice for the challenge of immunotherapy resistance.

Rapid, sensitive, and user-friendly detection of Pseudomonas aeruginosa using the RPA/CRISPR/Cas12a system.

BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is a life-threatening bacterium known for its rapid development of antibiotic resistance, posing significant challenges in clinical treatment, biosecurity, food safety, and environmental monitoring. Early and accurate identification of P. aeruginosa is crucial for effective intervention. METHODS: The lasB gene of P. aeruginosa was selected as the target for the detection. RPA primers for recombinase polymerase amplification (RPA) and crRNA for CRISPR/Cas12a detection were meticulously designed to target specific regions within the lasB gene. The specificity of the RPA/CRISPR/Cas12a detection platform was assessed using 15 strains. The detection limit of RPA/CRISPR/Cas12a detection platform was determined by utilizing a pseudo-dilution series of the P. aeruginosa DNA. The practical applicability of the RPA/CRISPR/Cas12a detection platform was validated by comparing it with qPCR on 150 samples (35 processed meat product samples, 55 cold seasoned vegetable dishes, 60 bottled water samples). RESULTS: The RPA/CRISPR/Cas12a detection platform demonstrates high specificity, with no cross-reactivity with non-P. aeruginosa strains. This assay exhibits remarkable sensitivity, with a limit of detection (LOD) of 100 copies/µL for fluorescence assay and 101 copies/µL for the LFTS method. Furthermore, the performance of the RPA/CRISPR/Cas12a detection platform is comparable to that of the well-established qPCR method, while offering advantages such as shorter reaction time, simplified operation, and reduced equipment requirements. CONCLUSIONS: The RPA/CRISPR/Cas12a detection platform presents a straightforward, accurate, and sensitive approach for early P. aeruginosa detection and holds great promise for diverse applications requiring rapid and reliable identification.

LncRNA MALAT 1/miR-625-3p/HIF-1α axis regulates the EMT of hypoxia-induced RPE cells by activating NF-κB/snail signaling.

The retina may undergo structural and functional damage as a result of hypoxia, which could lead to permanent blindness. As competing endogenous RNAs (ceRNAs), lncRNAs are essential in eye disorders. The biological function of lncRNA MALAT 1 and its potential mechanisms in hypoxic-ischemic retinal diseases are still unknown. MALAT 1 and miR-625-3p expression alterations in hypoxia-treated RPE cells were examined using qRT-PCR. The target binding relationships between MALAT 1 and miR-625-3p, as well as between miR-625-3p and HIF-1α, were identified utilizing bioinformatics analysis and dual luciferase reporter assay. We observed that si-MALAT 1 and miR-625-3p mimic both reduced apoptosis and epithelial-mesenchymal transition (EMT) in hypoxic RPE cells, whereas si-MALAT 1 was reversed by miR-625-3p inhibitor. Further, we carried out a mechanistic investigation, and rescue assays demonstrated that MALAT 1 sponging miR-625-3p influenced HIF-1α expression and consequently took part in the NF-κB/Snail signaling pathway, which regulated apoptosis and EMT. In conclusion, our research had shown that the MALAT 1/miR-625-3p/HIF-1α axis drove the progression of hypoxic-ischemic retinal disorders and may serve as a promising predictive biomarker for their therapeutic and diagnostic targets.

Tropilaelaps mercedesae parasitism changes behavior and gene expression in honey bee workers.

Tropilaelaps mercedesae is one of the most problematic honey bee parasites and has become more threatening to the beekeeping industry. Tropilaelaps can easily parasitize immature honey bees (larvae and pupae) and have both lethal and sublethal effects on the individual worker bees. Our study for the first time experimentally assessed the effects of T. mercedesae on olfactory learning, flight ability, homing ability as well as transcriptional changes in parasitized adult honey bees. T. mercedesae infestation had negative impacts on olfactory associated function, flight ability, and homing rate. The volume of the mushroom body significantly increased in infested honey bees, which may be correlated to the lower sucrose responsiveness as well as lower learning ability in the infested bees. The gene expression involved in immune systems and carbohydrate transport and metabolism were significantly different between infested bees and non-infested bees. Moreover, genes function in cell adhesion play an essential role in olfactory sensory in honey bees. Our findings provide a comprehensive understanding of European honey bees in response to T. mercedesae infestation, and could be used to further investigate the complex molecular mechanisms in honey bees under parasitic stress.

Modified Podophyllotoxin Phenoxyacetamide Phenylacetate Derivatives: Tubulin/AKT1 Dual-Targeting and Potential Anticancer Agents for Human NSCLC.

Cancer is a major disease threatening human health worldwide, among which non-small-cell lung cancer (NSCLC) is the most deadly. Clinically, almost all anticancer drugs eventually fail to consistently benefit patients due to serious drug resistance. AKT is a key effector of the PI3K/AKT/mTOR pathway, which is closely related to the occurrence, development, and drug resistance of tumors. Herein, we first designed and synthesized 20 kinds of novel hybrid molecules targeting both tubulin and AKT based on a podophyllotoxin (PPT) skeleton through computer-aided drug design. By CCK8 assay, we screened the compound D1-1 (IC50 = 0.10 µM) with the strongest inhibitory activity against H1975 cells, and its activity was 100 times higher than PPT (IC50 = 12.56 µM) and 300 times higher than gefitinib (IC50 = 32.15 µM). Affinity analysis results showed that D1-1 not only retained the tubulin targeting of PPT but also showed strong AKT targeting. Subsequent pharmacological experiments showed that D1-1 significantly inhibited the proliferation and metastasis of H1975 cells and slightly induced their apoptosis by inhibiting both tubulin polymerization and the AKT pathway activation. Collectively, these data demonstrate that the novel hybrid molecule D1-1 may be an excellent lead compound for the treatment of human NSCLC as a dual inhibitor of tubulin and AKT.

Chemerin contributes to inflammatory responses and suppresses osteogenic differentiation in chronic periodontitis.

BACKGROUND: Chronic periodontitis (CP) is a common disease of oral cavity, and approximately 35% of adults suffered from CP. Therefore, its underlying mechanism needs to be explored for new therapeutic approaches. Chemerin, as a multifunctional adipokine, is found to be highly expressed in the gingival crevicular fluid (GCF), gingival tissues and the plasma of periodontitis patients. Thus, we aimed to uncover the underlying mechanism of chemerin in CP. METHODS: Thirty six CP patients and 25 healthy volunteers were enrolled. Periodontal ligament stem cells (PDLSCs) were isolated from CP patients and healthy ones, respectively. Then, normal PDLSCs or PDLSCs-differentiated osteoblasts were treated with different doses of recombinant human chemerin. RESULTS: Chemerin and inflammatory cytokines, including interleukin-1ß, interleukin-6, and tumor necrosis factor-α, were higher in the GCF and serum of CP patients than healthy ones. Moreover, chemerin was positively correlated with these three inflammatory cytokines, respectively, in CP patients. PDLSCs isolated from CP patients had higher expressions of chemerin and these cytokines than the ones isolated from normal individuals. Furthermore, chemerin dose-dependently increased inflammatory responses and inhibited osteogenic differentiation of PDLSCs. CONCLUSION: Chemerin accelerated inflammatory responses and suppressed osteogenic differentiation of PDLSCs, thus chemerin might sever as a therapeutic target of CP.

Effects of Aromatherapy Massage Combined with TCM Emotional Release Technique on Maternal and Neonatal Physical and Mental Health and Family Relationship in Patients with Postpartum Depression.

Objective: To explore the effects of aromatherapy massage combined with TCM emotional release technique on maternal and neonatal physical and mental health and family relationships in patients with postpartum depression. Methods: A The total number of participants in the study was 160, who were evenly distributed through random assignment into four groups of 40 in each group. This random assignment process was designed to ensure that each group was similar in terms of demographic characteristics and other potential confounding factors to increase the comparability and internal validity of the study. The 160 patients with postpartum depression admitted to the obstetrics department of the Hebei 3a Hospital were enrolled between April 2021 and May 2022, and they were randomly divided into control group, sweet orange aromatherapy massage group, emotional release technique group and combination group, 40 cases in each group. The negative emotions, stress state, mania, levels of neurotransmitters and family intimacy adaptability were compared in the four groups before and after intervention. Results: After the intervention, scores of a generalized anxiety disorder (GAD-7) and Edinburgh Postpartum Depression Scale (EPDS) in the combination group were higher than those in the other three groups, and were higher in the emotional release technique group and sweet orange aromatherapy massage group than control group (P < .05). After the intervention, scores of PTSD Checklist-Civilian Version (PCL) and 32-item hypomania checklist (HCL-32) were the highest in the control group, followed by the sweet orange aromatherapy massage group, emotional release technique group and combination group (P < .05). After the intervention, levels of 5-hydroxytryptamine (5-HT) and dopamine (DA) were the highest in the combination group, followed by the emotional release technique group, sweet orange aromatherapy massage group, and control group (P < .05), and adaptability level of family intimacy was also in the same order (P < .05). In the combined treatment group, generalized anxiety disorder score (GAD-7) and postpartum depression scale (EPDS) scores were increased compared with the control group, indicating increased symptom severity in these two areas. GAD-7 and EPDS scores also increased significantly in the emotional release technique group and the sweet orange aromatherapy massage group. Although the magnitude of the increase may be different, both interventions seemed to lead to an increase in anxiety and depressive symptoms. As the intervention progressed, the control group had the highest scores on the Post-Traumatic Stress Disorder Checklist-Citizen Version (PCL) and the Hyperactivity Checklist 32 (HCL-32), followed by the Sweet Orange Aromatherapy Massage Group and the Emotional Release Technique group and combined treatment group. This indicates that symptom severity was significantly higher in the control group than in the other intervention groups in both areas. Levels of serotonin (5-HT) and dopamine (DA) increased in different groups, the highest in the combined treatment group, followed by the emotional release technique group, sweet orange aromatherapy massage group and the control group. This may indicate that the combination treatment had a positive effect on modulating the levels of these neurotransmitters. The adaptation level of family intimacy also changed according to the same trend. The highest level was in the combined treatment group, followed by the emotional release technique group, the sweet orange aromatherapy massage group and the control group. This may mean that combined treatment has a positive impact on the adaptability of family relationships. Conclusion: Aromatherapy massage combined with an emotional release technique can reduce negative emotions, stress, and mania, improve positive emotions and family intimacy adaptability of patients. These findings have important clinical implications as they relate to the well-being of women and families in the postpartum period. Reducing negative emotions and stress will improve women's mental health and improve their quality of life. In addition, positive emotional support helps create a healthy family atmosphere and has a positive impact on society as a whole.

Methionine alleviates heat stress-induced ferroptosis in bovine mammary epithelial cells through the Nrf2 pathway.

Heat stress (HS) triggers mammary gland degradation, accompanied by apoptosis and autophagy in bovine mammary epithelial cells, negatively affecting milk performance and mammary gland health. Ferroptosis is iron-mediated regulated cell death caused by over production of lipid peroxides, however, the relationship between ferroptosis and HS in bovine mammary epithelial cells has not been clarified. Methionine (Met) plays a notable role in alleviating HS affecting the mammary glands in dairy cows, but the underlying mechanisms require further exploration. Therefore, we evaluated the regulatory effect and mechanism of Met in alleviating HS-induced ferroptosis by using bovine mammary epithelial cell line (MAC-T) as an in vitro model. The results showed that Met improved cell vitality, restored mitochondrial function; reduced the content of various reactive oxygen species (ROS), especially hydrogen peroxide (H2O2) and superoxide anion (O2·-); had positive effects on antioxidant enzyme activity, namely glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). More importantly, Met reduced labile iron protein (LIP) levels; increased iron storage and simultaneously decreased the levels of lipid reactive oxygen species (lipid ROS) and malondialdehyde (MDA), which all caused by HS in MAC-T. Mechanistically, Met increased the protein expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7, member 11 (SLC7A11) and ferritin heavy chain 1 (FTH1) by activating nuclear factor E2-related factor 2 (Nrf2) expression. Additionally, the protection effect of Met was cut off in MAC-T cells after interference with Nrf2, manifesting in decresing the protein expression levels of GPX4, SLC7A11 and FTH1,and increasing the levels of LIP and lipid ROS. Our findings indicate that Met eases HS-induced ferroptosis in MAC-T through the Nrf2 pathway, revealing that Met produces a marked effect on easing HS-induced bovine mammary gland injury in dairy cows.

Comprehensive Profiling of ceRNA (circRNA-miRNA-mRNA) Networks in Hypothalamic-Pituitary-Mammary Gland Axis of Dairy Cows under Heat Stress.

Heat stress (HS) is directly correlated with mammary gland dysfunction and the hypothalamic-pituitary-mammary gland (HPM) axis is involved in regulating stress responses and lactation in dairy cows. Circular RNAs (circRNAs) play major roles in regulating transcription and post-transcription but their expression in the HPM axis of dairy cows under HS is still unclear. In the present study, we performed RNA sequencing to identify diferentially expressed (DE) circRNAs, DE microRNAs(miRNAs) and DEmRNAs, and performed bioinformatics analysis on those in HPM axis-related tissues of heat-stressed and normal cows. A total of 1680, 1112 and 521 DEcircRNAs, 120, 493 and 108 DEmiRNAs, 274, 6475 and 3134 DEmRNAs were identified in the hypothalamic, pituitary, and mammary gland tissues, respectively. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses indicated that the MAPK signaling pathway is potentially a key pathway. Competitive endogenous RNA (ceRNA) networks related to HS response and lactation regulation were established in three tissues. In conclusion, our results indicate that HS induces differential circRNA expression profiles in HPM axis-related tissues, and the predicted ceRNA network provides a molecular basis for regulating the stress response and lactation regulation in heat-stressed dairy cows.

Recovery and genetic characterization of black queen cell virus.

Black queen cell virus (BQCV) is a severe threat to the honeybee (Apis mellifera) worldwide. Although several BQCV strains have been reported in China, the molecular basis for BQCV pathogenicity has not been well understood. Thus, a reverse genetic system of BQCV is required for studying viral replication and its pathogenic mechanism. Here, the complete genome sequence of BQCV was obtained from honeybees using reverse transcription PCR (RT-PCR), namely a BQCV China-GS1 strain (KY741959). Then, a phylogenetic tree was built to analyse the genetic relationships among BQCV strains from different regions. Our results showed that the BQCV China-GS1 contained two ORFs, consistent with the known reference strains, except for the BQCV China-JL1 strain (KP119603). Furthermore, the infectious clone of BQCV was constructed based on BQCV China-GS1 using a low copy vector pACYC177 and gene recombination. Due to the lack of culture cells for bee viruses, we infected the healthy bees with infectious clone of BQCV, and the rescued BQCV resulted in the recovery of recombinant virus, which induced higher mortality than those of the control group. Immune response after inoculated with BQCV further confirmed that the infectious clone of BQCV caused the cellular and humoral immune response of honeybee (A. mellifera). In conclusion, the full nucleotide sequence of BQCV China-GS1 strain was determined, and the infectious clone of BQCV was constructed in this study. These data will improve the understanding of pathogenesis and the host immune responses to viral infection.

Construction and functional enrichment analysis of the competitive endogenous RNA regulatory network for nonarteritic anterior ischemic optic neuropathy based on high-throughput sequencing.

Based on the transcriptome high-throughput sequencing of nonarteritic anterior ischemic optic neuropathy (NAION), this study constructed a competitive endogenous RNA (ceRNA) network, enriched and analyzed it, screened long noncoding (lnc)RNAs and circular (circ)RNAs that may participate in the competitive endogenous mechanism in NAION, and inferred its function. Four milliliters of peripheral blood from NAION patients and the control group was extracted from clinical samples, transcriptome high-throughput sequencing was performed, and the sequencing data were visualized. Based on the principle of the ceRNA network, the lncRNA-micro (mi)RNA-messenger (m)RNA interaction axis and circRNA-miRNA‒mRNA interaction axes were constructed. The differentially expressed genes (DEGs) in the interaction axis were enriched and analyzed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), and the functions and signalling pathways of lncRNAs and circRNAs in the interaction network were speculated. Fifty-one circRNAs were differentially expressed in the sequencing data: 25 were upregulated, and 26 were downregulated. For 996 differentially expressed lncRNAs, 317 were upregulated and 679 were downregulated, and for 1161 differentially expressed mRNAs, 698 were upregulated and 463 were downregulated. Thirty-three differentially expressed miRNAs, upregulated miRNA 18 and downregulated miRNA 15 were identified. After screening, 13 coexpressed mRNAs, 15 lncRNAs, and 3 miRNAs were finally constructed in the lncRNA-miRNA-mRNA network, and the circRNA-miRNA-mRNA network was constructed by 159 mRNAs, 26 miRNAs, and 34 circRNAs. In the lncRNA network, GO enrichment analysis obtained 182 biological processes, 12 cell components and 38 molecular functions, which are related mainly to the regulation of the activity of proteins and enzymes such as cyclic nucleotide-dependent protein kinase activity and magnesium ion-dependent protein serine/threonine phosphatase activity. KEGG analysis involved mainly the forkhead box O (FoxO) signalling pathway, apelin signalling pathway, etc. In the circRNA enrichment results, 353 biological processes, 52 cell components, and 45 molecular functions were obtained, involving mainly calcium channel regulation, neutrophil activation, mRNA transport, and metabolism. KEGG mainly involved the Wnt signalling pathway, apelin signalling pathway, Hippo signalling pathway, oxytocin signalling pathway, etc. This paper provides a new idea for lncRNAs and circRNAs to mediate the occurrence and development of NAION through the ceRNA mechanism. This study lays a foundation for the in-depth study of the pathogenesis of NAION.

Nicotinamide mononucleotide alleviates heat stress-induced oxidative stress and apoptosis in BMECs through reducing mitochondrial damage and endoplasmic reticulum stress.

Heat stress is directly correlated to mammary gland dysfunction in dairy cows, especially in summer. Abnormally high environmental temperature induces oxidative stress and apoptosis in bovine mammary epithelial cells (BMECs). Nicotinamide mononucleotide (NMN) has beneficial effects in maintaining the cellular physiological functions. In this study, we evaluate the protective effect of NMN on heat stress-induced apoptosis of BMECs and explore the potential underlying mechanisms. Our results showed that heat stress considerably decreased cell viability in BMECs, whereas pretreatment of BMECs with NMN (150 µM) for 24 h significantly alleviated the negative effects of heat stress on cells. NMN protected BMECs from heat stress-induced oxidative stress by inhibiting the excessive accumulation of reactive oxygen species (ROS) and increasing the activity of antioxidant enzymes. It also inhibited apoptosis by reducing the ratio of Bax/Bcl2 and blocking proteolytic the cleavage of Caspase-3 in heat stressed-BMECs. Importantly, NMN treatment could reduce mitochondrial damage through mediating the expression of mitochondrial fission and fusion-related genes, including Dynamin related protein 1 (Drp1), Mitochondrial fission 1 protein (Fis1), and Mitofusin1, 2 (MFN1, 2); and suppress endoplasmic reticulum stress through unfolded protein response regulator Glucose regulated protein 78 (GRP78), and downstream elements Recombinant activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP). Above all, our results demonstrate that NMN supplemention attenuates heat stress-induced oxidative stress and apoptosis in BMECs by maintaining mitochondrial fission and fusion, and regulating endoplasmic reticulum stress, which provides the convincing evidence that NMN has valuable potential in alleviating mammary gland injury of dairy cows caused by environmental heat stress.

[Analysis of a patient with Kallmann syndrome and a 45,X/46,XY karyotype].

OBJECTIVE: To explore the etiology of a patient with Kallmann syndrome (congenital hypogonadism and anosmia) and a 45,X/46,XY karyotype. METHODS: Peripheral venous blood samples were collected from the proband and his parents and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. RESULTS: The proband was found to harbor compound heterozygous variants of the PROKR2 gene, namely c.533G>C (p.W178S) and c.308C>T (p.A103V), which were inherited from his father and mother, respectively. The two variants were respectively predicted to be likely pathogenic and variant of unknown significance, respectively. CONCLUSION: The reduced chromosomal mosaicism might have caused no particular clinical manifestations in this patient. For patients with features of Kallmann syndrome, genetic testing is conducive to early diagnosis and can provide a basis for genetic counseling and clinical treatment.

Synergistic Effect by Combining a gp120-Binding Protein and a gp41-Binding Antibody to Inactivate HIV-1 Virions and Inhibit HIV-1 Infection.

Acquired immune deficiency syndrome (AIDS) has prevailed over the last 30 years. Although highly active antiretroviral therapy (HAART) has decreased mortality and efficiently controlled the progression of disease, no vaccine or curative drugs have been approved until now. A viral inactivator is expected to inactivate cell-free virions in the absence of target cells. Previously, we identified a gp120-binding protein, mD1.22, which can inactivate laboratory-adapted HIV-1. In this study, we have found that the gp41 N-terminal heptad repeat (NHR)-binding antibody D5 single-chain variable fragment (scFv) alone cannot inactivate HIV-1 at the high concentration tested. However, D5 scFv in the combination could enhance inactivation activity of mD1.22 against divergent HIV-1 strains, including HIV-1 laboratory-adapted strains, primary HIV-1 isolates, T20- and AZT-resistant strains, and LRA-reactivated virions. Combining mD1.22 and D5 scFv exhibited synergistic effect on inhibition of infection by divergent HIV-1 strains. These results suggest good potential to develop the strategy of combining a gp120-binding protein and a gp41-binding antibody for the treatment of HIV-1 infection.

Tea consumption and risk of diabetes in the Chinese population: a multi-centre, cross-sectional study.

The aim of the present study was to explore the influence of tea consumption on diabetes mellitus in the Chinese population. This multi-centre, cross-sectional study was conducted in eight sites from south, east, north, west and middle regions in China by enrolling 12 017 subjects aged 20-70 years. Socio-demographic and general information was collected by a standardised questionnaire. A standard procedure was used to measure anthropometric characteristics and to obtain blood samples. The diagnosis of diabetes was determined using a standard 75-g oral glucose tolerance test. In the final analysis, 10 825 participants were included and multiple logistic models and interaction effect analysis were applied for assessing the association between tea drinking with diabetes. Compared with non-tea drinkers, the multivariable-adjusted OR for newly diagnosed diabetes were 0·80 (95 % CI 0·67, 0·97), 0·88 (95 % CI 0·71, 1·09) and 0·86 (95 % CI 0·67, 1·11) for daily tea drinkers, occasional tea drinkers and seldom tea drinkers, respectively. Furthermore, drinking tea daily was related to decreased risk of diabetes in females by 32 %, elderly (>45 years) by 24 % and obese (BMI > 30 kg/m2) by 34 %. Moreover, drinking dark tea was associated with reduced risk of diabetes by 45 % (OR 0·55; 95 % CI 0·42, 0·72; P < 0·01). The results imply that drinking tea daily was negatively related to risk of diabetes in female, elderly and obese people. In addition, drinking dark tea was associated with decreased risk of type 2 diabetes mellitus.

Coxsackievirus B3 infection induces changes in the expression of numerous piRNAs.

Piwi-interacting RNAs (piRNAs) play pivotal roles in spermatogenesis and are widely distributed among somatic tissues. However, little is known about piRNAs in HeLa cells infected with coxsackievirus B3 (CVB3). In this study, we systematically investigated changes in piRNA expression in HeLa cells infected with CVB3 using high-throughput sequencing technology. piRNA expression profiles in CVB3-infected HeLa cells were examined at 3, 6 and 9 h postinfection (pi). Of the 32,826 piRNAs that were annotated in the NCBI database, 151,571, 89,698 and 76,626 piRNAs were detected in CVB3-infected HeLa cells at 3, 6 and 9 h pi, respectively. Compared with normal cells, 211, 72 and 94 piRNAs were differentially expressed in CVB3-infected HeLa cells at 3, 6 and 9 h pi, respectively. Thirteen piRNAs, including four novel piRNAs, exhibited concurrent changes in CVB3-infected HeLa cells. The changes in the expression of these 13 piRNAs was confirmed in CVB3-infected HeLa cells and 293T cells by stem-loop RT-qPCR at 3, 6 and 9 h pi. The target genes of 13 piRNAs were predicted. The four novel piRNAs were associated with LTR/ERV, LINE/L1 and LTR/ERVK repetitive elements located on different chromosomes. These findings may promote a better understanding of the regulatory mechanism of pathophysiological changes induced by CVB3 infection.

The adverse maternal and perinatal outcomes of adolescent pregnancy: a cross sectional study in Hebei, China.

BACKGROUND: The adverse pregnancy outcomes caused by teenage pregnancy are major public health problems with significant social impact. While China is the most populous country in the world, and 8.5% of the women aged 10-50 years are adolescent women, we aimed to analyze the adverse maternal and perinatal outcomes of the adolescent pregnancy in Hebei Province, China. METHODS: There were 238,598 singleton pregnant women aged 10-34 years from January 1, 2013 to December 31, 2017 in the database of Hebei Province Maternal Near Miss Surveillance System (HBMNMSS). The 238,598 pregnant women were divided into two groups: adolescent group (aged 10-19 years) and adult group (aged 20-34 years). The adolescent group was divided into two subgroups (aged 10-17 years, aged 18-19 years), the adult group was divided into two subgroups (aged 20-24 years, aged 25-34 years). We compared the risk of adverse pregnancy outcomes using univariate and multivariate logistic regression. We also made a stratified analysis of nulliparous and multiparous adolescent pregnancy. RESULTS: Compared with women aged 20-34 years, women aged 10-19 years had lower risk of cesarean delivery [adjusted risk ratio (aRR): 0.75, 95% confidence interval (CI): 0.70-0.80], gestational diabetes mellitus (GDM) (aRR: 0.55, 95%CI: 0.41-0.73). Women aged 10-19 years had higher risk of preterm delivery (aRR: 1.76, 95%CI: 1.54-2.01), small for gestational age (SGA) (aRR: 1.19, 95%CI: 1.08-1.30), stillbirth (aRR: 2.58, 95%CI: 1.83-3.62), neonatal death (aRR: 2.63, 95%CI: 1.60-4.32). The adolescent women aged 10-17 years had significantly higher risk of stillbirth (aRR: 5.69, 95%CI: 3.36-9.65) and neonatal death (aRR: 7.57, 95%CI: 3.74-15.33) compared with the women aged 25-34 years. Younger adults (20-24 years) also had higher risks of preterm delivery (aRR: 1.26, 95%CI: 1.20-1.32), stillbirth (aRR: 1.45, 95%CI: 1.23-1.72), and neonatal death (aRR: 1.51, 95%CI: 1.21-1.90) compared with women aged 25-34 years. The structural equation model showed that preterm delivery and cesarean delivery had an indirect effect on neonatal death in adolescent pregnancy. CONCLUSIONS: The adolescent pregnancy was related to adverse perinatal (fetal and neonatal) outcomes, such as preterm delivery, stillbirth and neonatal death, especially in younger adolescent pregnancies.

Broad-Spectrum Coronavirus Fusion Inhibitors to Combat COVID-19 and Other Emerging Coronavirus Diseases.

In the past 17 years, three novel coronaviruses have caused severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the coronavirus disease 2019 (COVID-19). As emerging infectious diseases, they were characterized by their novel pathogens and transmissibility without available clinical drugs or vaccines. This is especially true for the newly identified COVID-19 caused by SARS coronavirus 2 (SARS-CoV-2) for which, to date, no specific antiviral drugs or vaccines have been approved. Similar to SARS and MERS, the lag time in the development of therapeutics is likely to take months to years. These facts call for the development of broad-spectrum anti-coronavirus drugs targeting a conserved target site. This review will systematically describe potential broad-spectrum coronavirus fusion inhibitors, including antibodies, protease inhibitors, and peptide fusion inhibitors, along with a discussion of their advantages and disadvantages.