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With the improper application of fungicides, Phytophthora sojae begins to develop resistance to fungicides, and biological control is one of the potential ways to control it. We screened two strains of Bacillus; Bacillus amyloliquefaciens JDF3 and Bacillus subtilis RSS-1, which had an efficient inhibitory effect on P. sojae. They could inhibit mycelial growth, the germination of the cysts, and the swimming of the motile zoospores. To elucidate the response of P. sojae under the stress of B. amyloliquefaciens and B. subtilis, and the molecular mechanism of biological control, comparative transcriptome analysis was applied. Transcriptome analysis revealed that the expression gene of P. sojae showed significant changes, and a total of 1616 differentially expressed genes (DEGs) were detected. They participated in two major types of regulation, namely “specificity” regulation and “common” regulation. They might inhibit the growth of P. sojae mainly by inhibiting the activity of ribosome. A pot experiment indicated that B. amyloliquefaciens and B. subtilis enhanced the resistance of soybean to P. sojae, and their control effects of them were 70.7% and 65.5%, respectively. In addition, B. amyloliquefaciens fermentation broth could induce an active oxygen burst, NO production, callose deposition, and lignification. B. subtilis could also stimulate the systemic to develop the resistance of soybean by lignification, and phytoalexin.

Sodium iodate (SI) is a widely used oxidant for generating retinal degeneration models by inducing the death of retinal pigment epithelium (RPE) cells. However, the mechanism of RPE cell death induced by SI remains unclear. In this study, we investigated the necrotic features of cultured human retinal pigment epithelium (ARPE-19) cells treated with SI and found that apoptosis or necroptosis was not the major death pathway. Instead, the death process was accompanied by significant elevation of intracellular labile iron level, ROS, and lipid peroxides which recapitulated the key features of ferroptosis. Ferroptosis inhibitors deferoxamine mesylate (DFO) and ferrostatin-1(Fer-1) partially prevented SI-induced cell death. Further studies revealed that SI treatment did not alter GPX4 (glutathione peroxidase 4) expression, but led to the depletion of reduced thiol groups, mainly intracellular GSH (reduced glutathione) and cysteine. The study on iron trafficking demonstrated that iron influx was not altered by SI treatment but iron efflux increased, indicating that the increase in labile iron was likely due to the release of sequestered iron. This hypothesis was verified by showing that SI directly promoted the release of labile iron from a cell-free lysate. We propose that SI depletes GSH, increases ROS, releases labile iron, and boosts lipid damage, which in turn results in ferroptosis in ARPE-19 cells.

Background The aim of this study was to evaluate the predictive value of the hematological parameters in the identification of human cytomegalovirus (CMV) infection in infants less than 3 months. Methods A single‐center, observational study of infants with CMV infection was conducted retrospectively. Routine blood parameters were analyzed in CMV‐infected infants and controls with no differences of birthweight, sex, gestational age at birth, and date of admission. Furthermore, receiver‐operating curve was used to assess the predictive value of the hematological parameters for CMV infection. Results One hundred ninety cases with CMV infection were studied retrospectively. Compared with the control group, there were significant differences in the white blood cell count, neutrophil count, lymphocyte count, platelet count, hemoglobin, neutrophil‐to‐lymphocyte (NLR), platelet‐to‐lymphocyte (PLR), and lymphocyte‐to‐monocyte (LMR) for the patients with CMV infection (all p < 0.001). The best predicted values for CMV infection based on the area under the curve (AUC) were NLR and PLR with the optimal cut‐off value of 0.28 and 65.36. NLR‐PLR score of 0, 1, or 2 based on an elevated NLR (>0.28), an elevated PLR (>65.36), or both. NLR‐PLR score for CMV infection prediction yielded higher AUC values than NLR or PLR alone (0.760 vs. 0.689, 0.689; p < 0.001). Conclusions The NLR combined with PLR is potentially useful as a predictor of CMV infection in infants less than 3 months. NLR‐PLR score for CMV infection prediction yielded higher AUC values than NLR or PLR alone (0.760 vs. 0.689, 0.689; p < 0.001). Therefore, the NLR combined with PLR is potentially useful as a predictor of CMV infection in infants less than 3 months.

Dysregulated autophagy leads to autoimmune diseases including rheumatoid arthritis (RA). Arsenic trioxide (ATO) is a single agent used for the treatment of acute promyelocytic leukemia and is highly promising for other malignancies but is also attractive for RA, although its relationship with autophagy remains to be further clarified and its application optimized. For the first time, we report a defective functional module of autophagy comprising the Vitamin D receptor (VDR), PPAR-γ, microtubule-associated protein 1 light-chain 3 (LC3), and p62 which appears in RA synovial fibroblasts. ATO alleviated RA symptoms by boosting effective autophagic flux through significantly downregulating p62, the inflammation and catabolism protein. Importantly, low-dose ATO synergizes with Vitamin D in RA treatment.

Cognitive impairment is a core feature of schizophrenia, which is aggravated by antipsychotics-induced metabolic disturbance and lacks effective pharmacologic treatments in clinical practice. Our previous study demonstrated the efficiency of metformin in alleviating metabolic disturbance following antipsychotic administration. Here we report that metformin could ameliorate cognitive impairment and improve functional connectivity (FC) in prefrontal regions. This is an open-labeled, evaluator-blinded study. Clinically stable patients with schizophrenia were randomly assigned to receive antipsychotics plus metformin (N = 48) or antipsychotics alone (N = 24) for 24 weeks. The improvement in cognition was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Its association with metabolic measurements, and voxel-wise whole-brain FC with dorsolateral prefrontal cortex (DLPFC) subregions as seeds were evaluated. When compared to the antipsychotics alone group, the addition of metformin resulted in significantly greater improvements in the MCCB composite score, speed of processing, working memory, verbal learning, and visual learning. A significant time × group interaction effect of increased FC between DLPFC and the anterior cingulate cortex (ACC)/middle cingulate cortex (MCC), and between DLPFC subregions were observed after metformin treatment, which was positively correlated with MCCB cognitive performance. Furthermore, the FC between left DLPFC A9/46d to right ACC/MCC significantly mediated metformin-induced speed of processing improvement; the FC between left A46 to right ACC significantly mediated metformin-induced verbal learning improvement. Collectively, these findings demonstrate that metformin can improve cognitive impairments in schizophrenia patients and is partly related to the FC changes in the DLPFC. Trial Registration: The trial was registered with ClinicalTrials.gov (NCT03271866). The full trial protocol is provided in Supplementary Material.

Background Intrauterine infection/inflammation plays an important role in the development of lung injury and bronchopulmonary dysplasia (BPD) in preterm infants, While a multifactorial genesis is likely, mechanisms involved in BPD after intrauterine infection/inflammation are largely unknown. Recent studies have suggested microRNAs (miRNAs) are likely to play a role. Therefore, this study aimed to study the effects and mechanisms of intrauterine infection/inflammation on lung development, and to identify miRNAs related to lung injury and BPD. Methods An animal model of intrauterine infection/inflammation was established with pregnant SD rats endocervically inoculated with E.coli. The fetal and neonatal rats were observed at embryonic day (E) 17, 19, 21 and postnatal day (P) 1, 3, 7, 14, respectively. Body weight, lung weight, the expression levels of NLRP3, TNF-α, IL-lβ, IL-6, VEGF, Collagen I, SP-A, SP-B and SP-C in the lung tissues of fetal and neonatal rats were measured. Expression profiles of 1218 kinds of miRNAs in the lungs of neonatal rats were detected by miRNA microarray technique. Target genes of the identified miRNAs were predicted through online software. Results Intrauterine infection/inflammation compromised not only weight development but also lung development of the fetal and neonatal rats. The results showed significantly increased expression of NLRP3, TNF-α, IL-1β, IL-6, Collagen I, and significantly decreased expression of VEGF, SP-A, SP-B and SP-C in the fetal and neonatal rat lung tissues in intrauterine infection group compared to the control group at different observation time point ( P  < 0.05). Forty-three miRNAs with significant differential expression were identified. Possible target genes regulated by the identified miRNAs are very rich. Conclusions Intrauterine infection/inflammation results in lung histological changes which are very similar to those observed in BPD. Possible mechanisms may include NLRP3 inflammasome activation followed by inflammatory cytokines expression up-regulated, inhibiting the expression of pulmonary surfactant proteins, interfering with lung interstitial development. There are many identified miRNAs which target a wide range of genes and may play an important role in the processes of lung injury and BPD.

Background To investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on hospitalizations for neonatal infectious diseases. Methods We analyzed data for neonatal inpatients admitted at a tertiary academic hospital with a principal diagnosis of an infectious disease during January 2015 to December 2020. We compared hospitalizations in 2020 (COVID-19 cohort), corresponding with the impact of COVID-19 pandemic and associated containment measures, and the comparable 2015 to 2019 (pre-COVID-19 cohort). Results 14,468 cases admitted for neonatal infectious diseases were included in our study, with 1201 cases in the COVID-19 cohort and 13,267 cases in the pre-COVID-19 cohort. The leading causes of hospitalizations for neonatal infectious diseases remain being respiratory tract infections (median ratio = 0.461, 95% CI 0.335–0.551), sepsis (median ratio = 0.292, 95% CI 0.263–0.361), gastric intestinal infections (median ratio = 0.095, 95% CI 0.078–0.118) and dermatologic infections (median ratio = 0.058, 95% CI 0.047–0.083). The seasonality of neonatal infectious disease hospitalizations could be obviously observed, with the total number and the overall rate of hospitalizations for neonatal infectious diseases in the first and fourth quarters greater than that of hospitalizations for neonatal infectious diseases in the second and third quarters in each year (1362.67 ± 360.54 vs 1048.67 ± 279.23, P = 0.001; 8176/20020 vs 6292/19369, P < 0.001, respectively). Both the numbers and the proportions of hospitalizations for neonatal infectious diseases in different quarters of the COVID-19 cohort significantly decreased as compared with those forecasted with the data from the pre-COVID-19 cohort: the numbers per quarter (300.25 ± 57.33 vs 546.64 ± 100.43, P-value = 0.006), the first quarter (0.34 vs 0.40, P = 0.002), the second quarter (0.24 vs 0.30, P = 0.001), the third quarter (0.24 vs 0.28, P = 0.024), and the fourth quarter (0.29 vs 0.35, P = 0.003). Conclusions Despite the outbreak of the COVID-19 pandemic, the leading causes of hospitalizations for neonatal infectious diseases remain unchanged. The seasonality of neonatal infectious disease hospitalizations could be obviously observed. The numbers as well as the overall rates of hospitalizations for neonatal infectious diseases in the COVID-19 cohort dramatically declined with the impact of the COVID-19 pandemic and its mitigation measures.

Background Cognitive impairment is a prominent feature that adversely affects the long-term prognosis of schizophrenia; yet effective clinical strategies for treatment remain limited. Disruptions in the tricarboxylic acid (TCA) cycle and functional brain abnormalities in the hippocampus may underlie cognitive deficits, although the intrinsic connections between these factors have yet to be fully elucidated. Notably, metformin, a biguanide anti-hyperglycemic agent, has been shown to improve several cognitive domains in patients with schizophrenia and may have the potential to regulate the TCA cycle. Previously, we found the cognitive improvement effect of adding metformin. In this study, we will further explore the relationship between cognitive improvement and TCA cycle metabolites and brain function. Methods This study included 58 patients with schizophrenia who were in similar clinical conditions and assigned to 24-week 1500 mg metformin add-on treatment or the control group. We used the liquid chromatography tandem mass spectrometry (LC–MS/MS) method to detect the levels of key TCA cycle metabolites in the blood of schizophrenia patients, conducted MRI scans, and assessed clinical condition using the Positive and Negative Syndrome Scale (PANSS) and cognitive performance using the Chinese version of MATRICS Consensus Cognitive Battery (MCCB). Results Twenty-four weeks of metformin treatment downregulated levels of upstream lactic acid (− 80.81 (− 96.85, − 64.77) μg/mL at week 24) and pyruvic acid (− 17.51 (− 20.52, − 14.49) μg/mL at week 24), while upregulating levels of other seven downstream metabolites in TCA cycle (all p values < 0.001). Functional connectivity between left caudal hippocampus and right medio ventral occipital cortex (week 12, between-group difference =  − 0.334), and right caudal hippocampus and right middle frontal gyrus (week 24, between-group difference = 0.284) were significantly different between groups ( p  < 0.001). Moreover, metformin-improved cognition (working memory and verbal learning) and hippocampal functional connectivity (right caudal hippocampus and right middle frontal gyrus) were associated with changes in TCA cycle metabolites. Limitation Limited sample size and follow-up time, and lack of in-depth mechanism exploration. Conclusions Our results suggested that repurposing of metformin may have the potential to improve cognition by regulating energy metabolism pathways. Clinical trials registration NCT03271866. Graphical Abstract

Background The heterogeneity of cognitive impairments in schizophrenia has been widely observed. However, reliable cognitive boundaries to differentiate the subgroups remain elusive. The key challenge for cognitive subtyping is applying an integrated and standardized cognitive assessment and understanding the subgroup-specific neurobiological mechanisms. The present study endeavors to explore cognitive subgroups and identify their morphological features. Methods A total of 920 schizophrenia patients and 169 healthy controls were recruited. MATRICS Consensus Cognitive Battery was applied to assess cognitive performance and recognize cognitive subgroups through latent profile and latent transition analysis. Cortical thickness and gray matter volume were employed for the morphological features across subgroups. Results Four reproducible cognitive subgroups were identified, including multidomain-intact, executive-preserved, executive-deteriorated, and multidomain-deteriorated subgroup. After 12 weeks of follow-up, the cognitive characteristics of three out of the four subgroups kept stability, except for multidomain-deteriorated subgroup in which 48.8% of patients with improved cognition transited into the executive-deteriorated subgroup. Across subgroups, significant gradient features of brain structure were exhibited in fronto-temporal regions, hippocampus, and insula. Compared to healthy controls, multidomain-intact subgroup showed the most intact cognition and morphology, and multidomain-deteriorated subgroup with youngest age showed morphological decline in extensive regions. The remaining two subgroups showed intermediate cognitive performance, but could be distinguished by executive function and morphological differences in posterior cingulate cortex. Conclusions Our study provides novel insights into the heterogeneity of cognitive impairments in schizophrenia and the morphological features from cross-sectional and longitudinal levels, which could advance our understanding of complex cognition-morphology relationships and guide personalized interventions.

Advanced glycation end products (AGEs) are the compounds produced by non-enzymatic glycation of proteins, which are involved in diabetic-related complications. To investigate the potential anti-glycation activity of Myriocin (Myr), a fungal metabolite of Cordyceps, the effect of Myr on the formation of AGEs resulted from the glycation of bovine serum albumin (BSA) and the interaction between Myr and BSA were studied by multiple spectroscopic techniques and computational simulations. We found that Myr inhibited the formation of AGEs at the end stage of glycation reaction and exhibited strong anti-fibrillation activity. Spectroscopic analysis revealed that Myr quenched the fluorescence of BSA in a static process, with the possible formation of a complex (approximate molar ratio of 1:1). The binding between BSA and Myr mainly depended on van der Waals interaction, hydrophobic interactions and hydrogen bond. The synchronous fluorescence and UV-visible (UV-vis) spectra results indicated that the conformation of BSA altered in the presence of Myr. The fluorescent probe displacement experiments and molecular docking suggested that Myr primarily bound to binding site 1 (subdomain IIA) of BSA. These findings demonstrate that Myr is a potential anti-glycation agent and provide a theoretical basis for the further functional research of Myr in the prevention and treatment of AGEs-related diseases.