Search

IntroductionFusarium oxysporum f. sp. Lycopersici (Fol) is one of the most devastating plant pathogenic fungi, the causal agent of root rot for Atractylides macrocephala Koidz (AMK). An accurate rapid and convenient diagnosis for FoL detection is essential for determining management practices and preventing future losses for AMK.MethodsHere, we developed a novel method for Fol detection by integrating loop-mediated isothermal amplification (LAMP) assay and CRISPR/Cas12b detection in one-pot, and the whole reaction can simultaneously amplify and detect the target gene of Fol in one-step.ResultsThe total time of the present method is limited to 45 min and isothermally performed at 60°C. The limit of detection of this assay is 88.9 copies per reaction. The specificity of the LAMP-CRISPR/Cas12b method was 100% without any cross-reaction of other pathogens. A total of 24 nucleic acid samples were used to evaluate the performance of the LAMP-CRISPR/Cas12b method, including 12 with-Fol and 12 without-Fol. Compared with the gold standard results from real-time PCR, the present method provides a sensitivity of 100% (12/12), specificity of 100% (12/12), and consistency of 100% (24/24).DiscussionTogether, our preliminary results illustrated that the LAMP-CRISPR/Cas12b method is a rapid simple, and reliable tool for Fol diagnosis and could be applied in point-of-need phytopathogen detection.

IntroductionFusarium oxysporum is a significant soil-borne fungal pathogen that affects over 100 plant species, including crucial crops like tomatoes, bananas, cotton, cucumbers, and watermelons, leading to wilting, yellowing, growth inhibition, and ultimately plant death. The root rot disease of A. macrocephala, caused by F. oxysporum, is one of the most serious diseases in continuous cropping, which seriously affects its sustainable development.MethodsIn this study, we explored the interaction between A. macrocephala and F. oxysporum through integrated small RNA (sRNA) and degradome sequencing to uncover the microRNA (miRNA)–mediated defense mechanisms.ResultsWe identified colonization of F. oxysporum in A. macrocephala roots on day 6. Nine sRNA samples were sequenced to examine the dynamic changes in miRNA expression in A. macrocephala infected by F. oxysporum at 0, 6, and 12 days after inoculation. Furthermore, we using degradome sequencing and quantitative real-time PCR (qRT-PCR), validated four miRNA/target regulatory units involved in A. macrocephala–F. oxysporum interactions.DiscussionThis study provides new insights into the molecular mechanisms underlying A. macrocephala's early defense against F. oxysporum infection, suggesting directions for enhancing resistance against this pathogen.

BackgroundImproving the young college students’ national identity is crucial for ensuring social stability and fostering development during public health critical events such as COVID-19. Young college students’ recognition of national COVID-19 crisis governance capabilities can influence their national identity, and online participation in public health criticalevents may serve as a crucial role in shaping this intricate relationship. To investigate this possibility, the present study established an intermediary model to examine the impact of online participation in public health critical events on young college students’ recognition of national COVID-19 crisis governance capabilities and improvement of national identity.MethodsThis cross-sectional survey study employed a convenience sampling method to investigate a total of 3041 young college students in China. The correlations between study variables were analyzed using Spearman’s rank correlation. The mediation model was established using PROCESS Model 4 with 5000 bootstrap samples in SPSS. The bias-corrected bootstrap method provided statistical efficacy and identification interval estimation.ResultsYoung college students’ recognition of national COVID-19 crisis governance capabilities (r=0.729, P

ObjectiveHuman identical sequences of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) promoted the coronavirus disease 2019 (COVID-19) progression by upregulating hyaluronic acid (HA) via NamiRNA-enhancer network, based on previous experimental research. This study aimed to investigate the predictive value of HA for the severity of SARS-CoV-2 infection in the post-COVID-19 era.MethodsA total of 217 consecutive patients with COVID-19 were enrolled at Beijing Ditan Hospital between July 2023 and October 2023. HA levels were analyzed using biochemical detector. Logistic regression analysis was used to screen independent factors for severe COVID-19. The predictive performance of HA for severe infection was assessed by ROC curve. Furthermore, the relationship between HA levels and COVID-19 severity was investigated using multivariate logistic regression models after adjustment for potential confounders.ResultsAccording to the cut-off value of HA, COVID-19 patients were divided into HA < 90 ng/mL group (80 cases) and HA ≥ 90 ng/mL group (137 cases). High HA levels were positively associated with the severe SARS-CoV-2 infection, including elevated inflammatory indicators, severe lung involvement, prolonged clinical course, and higher incidence of respiratory failure and death (P < 0.05). Logistic regression analysis suggested that HA was an independent predictor of severe COVID-19 (OR = 4.540, 95% CI = 2.105-9.790, P < 0.001). ROC curve analysis showed that the AUC of HA for severe infection was 0.724. HA levels were significantly higher in COVID-19 cases compared to the healthy population (123.9 (82.6, 174.1) vs. 50.5 (37.8, 66.8), P < 0.001), but similar to those with non-SARS-CoV-2 lung infection (121.6 (78.5, 175.6) vs. 106.0 (66.5, 149.7), P = 0.244). We also found that the first COVID-19 infections had higher HA levels (118.8 (79.5, 174.3) vs. 85.0 (61.1, 128.8), P < 0.001) and a higher proportion of severe infection (37.1% vs. 21.3%, P = 0.043) than re-infections. However, HA expression failed to fully return to normal levels with infection recovery (204.7 (152.9, 242.2) vs. 97.0 (69.3, 137.3), P < 0.001).ConclusionHA was associated with severe SARS-CoV-2 infection and could be used as a novel serum biomarker to predict the risk of COVID-19 progression in the post-COVID-19 era.

BackgroundA growing number of studies have suggested that adolescents’ prosocial behavior can protect against depression and anxiety. It is known that anxiety and depression are often comorbid. However, it remains unclear if when depression is present, prosocial behavior remains protective against anxiety, and if when anxiety is present, prosocial behavior remains protective against depression. The purpose of this study was to determine the association of anxiety and depressive with prosocial behavior.MethodsA large representative sample of middle-school students was recruited for a cross-sectional study and completed standardized instruments (the Children’s Depression Inventory (CDI), Screen for Child Anxiety Related Emotional Disorders–Child version (SCARED-C), and Strengths and Difficulties Questionnaire (SDQ)). We used structural equation modeling (SEM) to examine the protective effect of prosocial behavior against anxiety when depression was present.ResultsA survey of 3,510 students was conducted, and the final analysis included 3,169 students, comprising 1,616 boys (51.0%) and 1,553 girls (49.0%), with a mean age of 13.09 years (SD = 1.31, range 11–16).The prevalence rates of anxiety and depression in early adolescents were 31.6 and 16.7%, respectively. More than two-thirds of depressed adolescents had comorbid anxiety, while more than one-third of anxious adolescents had comorbid depression. Regression models showed that compared with depressed adolescents, adolescents without depressive symptoms exhibited a significant negative correlation between prosocial behaviors and anxiety and depression (β = −0.01, p > 0.01, β = −0.06, p > 0.01; β = −0.11, p < 0.01, and β = −0.17, p < 0.01). There was no difference in the relationship between prosocial behavior and depression between anxious and non-anxious adolescents (p > 0.05).ConclusionAnxiety and depression are common in adolescence and are often comorbid disorders. However, the comorbidity is not symmetrical. Specifically, the protective effect of prosocial behavior against anxiety is weaker in depressed adolescents. Findings are discussed in light of related research and theory, and insights for intervention programs and future research are presented.

ObjectiveThis study sought to examine the impacts of a high dietary fiber cereal meal in comparison to conventional dietary management for diabetes on body weight, distribution of adipose tissue, and cardiovascular risk among individuals diagnosed with type 2 diabetes (T2DM).MethodsA cohort of 120 patients diagnosed with T2DM was enlisted as the study population and divided into two groups using a ratio of 2:1—namely, the W group (n=80) and the U group (n=40). The U group (control) received usual diet, while the W group (intervention) incorporated a high dietary fiber cereal meal in place of their regular staple food in addition to adhering to conventional diabetes dietary recommendations. The high dietary fiber cereal meal was based on whole grains, traditional Chinese medicinal foods, and prebiotics. A subsequent follow-up period of 3 months ensued, during which diverse parameters such as body mass index (BMI),waist-hip ratio (WHR), glycated hemoglobin (HbA1c),fasting blood glucose(FBG),C-peptide levels, blood pressure, blood lipids, high-sensitivity C-reactive protein (hsCRP),10-year cardiovascular disease (CVD) risk, and Lifetime CVD risk were assessed before and after the intervention.ResultsAmong the participants, a total of 107 successfully completed the intervention and follow-up, including 72 individuals from the W group and 35 from the U group. Following the intervention, both cohorts exhibited decrease in BMI, WHR, HbA1c, FBG, blood pressure, and blood lipid levels in contrast to their initial measurements. Remarkably, the improvements in BMI, WHR, HbA1c, FBG, total cholesterol (TC), triglycerides(TG), low-density lipoprotein cholesterol (LDL-C), the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C), and the ratio of 2-hour C-peptide (2hCP) to fasting C-peptide (FCP) were more marked within the W group, exhibiting statistically significant disparities (P

ObjectiveUrsodeoxycholic acid (UDCA) may reduce susceptibility to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection by downregulating angiotensin-converting enzyme 2 (ACE2), based on recent experimental investigation. This study aimed to determine the potential protective effect of UDCA against SARS-CoV-2 infection in patients with chronic liver disease.MethodsPatients with chronic liver disease receiving UDCA (taking UDCA ≥1 month) at Beijing Ditan Hospital between January 2022 and December 2022 were consecutively enrolled. These patients were matched in a 1:1 ratio to those with liver disease not receiving UDCA during the same period by using a propensity score matching analysis with nearest neighbor matching algorithm. We conducted a phone survey of coronavirus disease 2019 (COVID-19) infection during the early phase of the pandemic liberation (from 15 December 2022 to 15 January 2023). The risk of COVID-19 was compared in two matched cohorts of 225 UDCA users and 225 non-UDCA users based on patient self-report.ResultsIn the adjusted analysis, the control group was superior to the UDCA group in COVID-19 vaccination rates and liver function indicators, including γ-glutamyl transpeptidase and alkaline phosphatase (p < 0.05). UDCA was associated with a lower incidence of SARS-CoV-2 infection (UDCA 85.3% vs. control 94.2%, p = 0.002), more mild cases (80.0% vs. 72.0%, p = 0.047), and shorter median time from infection to recovery (5 vs. 7 days, p < 0.001). Logistic regression analysis showed that UDCA was a significant protective factor against COVID-19 infection (OR: 0.32, 95%CI: 0.16–0.64, p = 0.001). Furthermore, diabetes mellitus (OR: 2.48, 95%CI: 1.11–5.54, p = 0.027) and moderate/severe infection (OR: 8.94, 95%CI: 1.07–74.61, p = 0.043) were more likely to prolong the time from infection to recovery.ConclusionUDCA therapy may be beneficial in reducing COVID-19 infection risk, alleviating symptoms, and shortening the recovery time in patients with chronic liver disease. However, it should be emphasized that the conclusions were based on patient self-report rather than classical COVID-19 detection by experimental investigations. Further large clinical and experimental studies are needed to validate these findings.

BackgroundLiposarcomas (LPS) are mesenchymal malignancies with four principal subtypes presenting distinct molecular and clinical features. Pleomorphic liposarcoma (PLPS) is one of the rarest and most aggressive subtypes of LPS. Surgical resection is currently a preferred curative approach for localized PLPS. However, the prognosis of unresectable PLPS is extremely poor, and there is no standard treatment.Case presentationA 59-year-old Chinese woman was diagnosed with unresectable PLPS. The case was discussed and managed by specialists from a multidisciplinary team at Fudan Zhongshan Hospital. Preoperative radiotherapy (RT) of intensity-modulated radiation therapy (IMRT) at 50 Gy/25 Fx concurrently with the angiogenesis inhibitor anlotinib (8 mg, days 1–14, every 3 weeks) was prescribed to the patient. The dosage of anlotinib was increased to 10 mg after RT. After 6 months of treatment, the tumor had significantly shrunk and was successfully resected. Examination of the surgical specimens showed a pathological complete response (pCR). Until the latest follow-up (April 2022), no recurrence was observed, and disease-free survival has exceeded 14 months.ConclusionThis case sheds light on the probability that perioperative RT combined with an angiogenesis inhibitor can be effectively used in PLPS, which is resistant to chemotherapy and usually considered to have a poor prognosis. Further studies with randomized controlled clinical trials will improve our knowledge of this preoperative treatment strategy.

IntroductionAs a special vulnerable group, the physical and mental health of elderly cancer patients has attracted much attention. However, few studies have focused on the impact of nurses’ mental state on the mental health of elderly cancer patients during the COVID-19 pandemic. In response to this literature gap, this study aims to explore the impact of nurses’ psychological capital on the satisfaction of elderly cancer patients. The job demands-resources model (JD-R) is used to further investigate how work engagement and job resources of nurses affect this relationship.MethodsThe questionnaire survey was used to collect data, participants included 230 elderly cancer patients and their nurses from a tertiary first-class cancer hospital in China. Partial least squares structural equation modeling (PLS-SEM) was conducted with SmartPLS 3.3.9.ResultsNurses’ psychological capital has a significant positive impact on the satisfaction of elderly cancer patients during the COVID-19 pandemic. Nurses’ work engagement is an important mechanism for their psychological capital to affect the satisfaction of elderly cancer patients. In addition, nurses’ job resources positively moderate the relationship between their psychological capital and work engagement. The positive relationship between psychological capital and work engagement of nurses is stronger when they have abundant job resources.DiscussionThese findings suggest that healthcare organizations should take the psychological capital of medical staff as an important means to improve their competitive advantage. It can improve the quality of medical services to obtain good performance by effectively developing and managing the psychological capital of medical staff. In addition, healthcare organizations should recognize the importance of providing adequate job resources for medical staff.

BackgroundAs some countries announced to remove Coronavirus Disease 2019 (COVID-19) border, it indicates that the COVID-19 may have entered its terminal stage. In this COVID-19 pandemic, the mental health of frontline healthcare workers (HCWs) experienced unprecedented challenges. However, the impact of the COVID-19 pandemic on mental health among frontline HCWs lacks a high-quality and long-term systematic review and meta-analysis.MethodsWe conducted a systematic review and meta-analysis according to PRISMA guidelines. The system searches EMBASE, MEDLINE, PsycINFO, Cochrane Library, ScienceNet, and ERIC. Analyze the mental health problems of frontline HCWs in different regions and periods, including insomnia, stress, anxiety and depression. This study was registered in PROSPERO under the number CRD42021253821.ResultsA total of 19 studies on the effects of COVID-19 pandemic on mental health among frontline HCWs were included in this study. The overall prevalence of insomnia was 42.9% (95% CI, 33.9–51.9%, I2 = 99.0%) extracted from data from 14 cross-sectional studies (n = 10 127), 1 cohort study (n = 4,804), and 1 randomized controlled trial (RCT; n = 482) in 10 countries. The overall prevalence of stress was 53.0% (95% CI, 41.1–64.9%, I2 = 78.3%) extracted from data from nine cross-sectional studies (n = 5,494) and 1 RCT study (n = 482) from eight countries. The overall prevalence of anxiety and depression was 43.0% (95% CI, 33.8–52.3%, I2 = 99.0%) and 44.6% (95% CI, 36.1–53.1%, I2 = 99.0%) extracted from data from 17 cross-sectional studies (n = 11,727), one cohort study (n = 4,804), and one RCT study (n = 482) from 12 countries. The prevalence of stress and depression was higher in 2020, while the prevalence of insomnia and anxiety was higher in 2021. The prevalence of mental health problems among physicians was higher than that of other frontline HCWs. The prevalence of mental health problems among frontline HCWs is higher in South America and lower in North America.ConclusionsThis systematic review and meta-analysis showed that the COVID-19 pandemic have significant effects on mental health among frontline HCWs. The overall prevalence of insomnia, stress, anxiety and depression among frontline HCWs is high. Therefore, the health policy-makers should pay attention to and respond to the mental health problems of frontline HCWs in the context of public health emergencies.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/.

With the service-dominant logic gradually replacing the traditional commodity-dominant reason, co-creating value with consumers has become an essential marketing practice for enterprises. As a critical information carrier in enterprise marketing communication, the co-creation signal impacts co-creation observers. Enterprises are now exploring how to effectively release co-creation signals to attract most observers to participate in value creation activities actively. Based on self-determination theory, this study investigates the influence mechanism of co-creation signals on observers’ willingness to co-create and the moderating role of mental simulation through the experimental method. The conclusions are as follows: (a) The co-creation signal has a significant positive effect on the co-creation intention of observers. Self-designed co-creation signals generate more important co-creation willingness than self-produced co-creation signals; (b) Self-determination and its dimensions mediate the relationship between co-creation signals and the observer’s co-creation willingness; and (c) Mental simulation moderates the relationship between co-creation signal and self-determination. This study has important theoretical significance in enriching co-creation signals and mental simulation research. It also provides management implications for enterprises to release co-creation signals and optimize co-creation marketing practices effectively.

Aging-related muscle loss is a hallmark of aging and is the cause of some negative outcomes. An optimized diet and supplements have a positive effect in slowing down the process of muscle loss. D-galactose(d-gal) has been used widely to develop aging model. This study explored the beneficial effects of whey protein peptides (WPPs) on sarcopenia in d-gal-induced aging mice. A total of 72 SPF male C57BL/6N mice were used in this study. Sixty mice were modeled by injected intraperitoneally with d-gal (100 mg/kg body weight for 6 weeks), and the other 12 mice were used as control, and injected with the same amount of normal saline. After 6 weeks, the modeled mice were randomly divided into the model control group, whey protein group (1.5 g/kg*bw), and three WPPs intervention groups (0.3 g/kg*bw, 1.5 g/kg*bw, 3.0 g/kg*bw), according to serum malondialdehyde (MDA) level. The test samples were orally given to mice by daily garaged. During the 30 days intervention period, the model control group, whey protein group, and WPPs group continued receiving intraperitoneal injections of d-gal, whereas the control group continued receiving intraperitoneal injections of normal saline. The results showed that WPPs could significantly improve the grip strength of aged mice. WPPs could significantly increase lean mass of aged mice and increase muscle weight of gastrocnemius and extensor digitorum longus. WPPs could significantly increase the level of insulin-like growth factor-1 (IGF-1) and reduce level of interleukin (IL)-1, IL-6, tumor necrosis factor-alpha (TNF-α) in serum. WPPs could affect the muscle fiber size in d-gal-induced aging mice. Its specific mechanism may be related to the activation of IGF-1/Akt/mTOR protein synthesis signaling pathway and reduction of the level of inflammation. These results indicate that WPPs can improve aging-related sarcopenia. Compared with whey protein, WPPs supplement seems a better form for sarcopenia.

The uterus is the core place for breeding new life. The balance and imbalance of uterine microecology can directly affect or even dominate the female reproductive health. Emerging data demonstrate that endometrial microbiota, endometrium and immunity play an irreplaceable role in regulating uterine microecology, forming a dynamic iron triangle relationship. Up to nowadays, it remains unclear how the three factors affect and interact with each other, which is also a frontier topic in the emerging field of reproductive tract microecology. From this new perspective, we aim to clarify the relationship and mechanism of the interaction of these three factors, especially their pairwise interactions. Finally, the limitations and future perspectives of the current studies are summarized. In general, these three factors have a dynamic relationship of mutual dependence, promotion and restriction under the physiological or pathological conditions of uterus, among which the regulatory mechanism of microbiota and immunity plays a role of bridge. These findings can provide new insights and measures for the regulation of uterine microecology, the prevention and treatment of endometrial diseases, and the further multi-disciplinary integration between microbiology, immunology and reproductive medicine.

Previous studies suggest that patients with nephrolithiasis exhibit dysbiosis in their gut microbiota, but those studies were conducted in calcium oxalate stone patients. We aimed to explore the association of gut microbiota and biochemical features of renal uric acid stone (UAS) patients in a Chinese population and identify the related bacteria that may affect the pathopoiesis of UAS. A case-control study of 117 patients with UAS, 123 patients with gout, and 135 healthy controls were included from January 2014 to October 2020. For each subject, data on demographics, biochemical parameters of blood and urine were analyzed. Fifteen patients with gout, 16 patients with UAS, 17 UAS patients with gout, and 17 healthy subjects were enrolled and provided fecal samples. The characteristics of gut microbiota were explored by using 16S ribosomal RNA (rRNA) gene sequencing and analyzed by using a combination of software mother and R. Hyperuricemia was the main risk factor for the development of gout and UAS. Obesity, dyslipidemia, and aciduria were unique risk factors for UAS patients. The richness, diversity, and relative abundance of dominant bacteria at the phylum and genus levels of gut microbiota in UAS patients were significantly distinct from other subjects. Abundance of Bacteroides and Fusobacterium was significantly positively correlated with the serum uric acid (UA) level of UAS patients. Fusobacteria was involved in the metabolism and degradation of certain short-chain fatty acids, amino acids, and sugars in pathopoiesis of UAS, and inhibited their synthesis pathways. Fusobacteria may be related to the pathogenesis of UAS, and this finding contributes to the personalized treatment of UAS from the perspective of maintaining micro-ecological equilibrium in gut.

BackgroundDrug resistance remains a serious challenge to rituximab therapy in B-NHL (B cell non-Hodgkin’s lymphoma). CDC (complement-dependent cytotoxicity) has been proposed as a major antitumor mechanism of rituximab, and direct abrogation of CD59 function partially restores rituximab sensitivity with high efficacy. However, universal blockade of CD59 may have deleterious effects on normal cells. Sp1 regulates constitutive CD59 expression, whereas NF-κB and CREB regulate inducible CD59 expression.MethodsImmunohistochemistry (IHC) assay was used to detect the expression levels of CD59 and other related molecules. Quantitative Real-time PCR (RT-PCR) analysis was used to explore the levels of transcripts in the original and resistant cells. We chose LY8 cells to test the effects of NF-κB and CBP/p300 inhibition on CD59 expression using flow cytometry (FACS). Immunoblotting analysis was employed to detect the effects of curcumin and POH. The in vitro and in vivo experiments were used to evaluate the toxicity and combined inhibitory effect on tumor cells of curcumin and POH.ResultsWe demonstrated that herbal (curcumin and perillyl alcohol) blockade of NF-κB specifically suppresses the expression of inducible CD59 but not CD20, thus sensitizing resistant cells to rituximab-mediated CDC. Moreover, activation of NF-κB and CREB is highly correlated with CD59 expression in B-NHL tissues.ConclusionsOur findings suggest the potential of CD59 expression as a predictor of therapeutic efficacy of NF-κB inhibitors in clinical application as well as the rationality of a NF-κB inhibitor-rituximab regimen in B-NHL therapy.

Ulcerative colitis (UC), a chronic, nonspecific inflammatory bowel disease characterized by continuous and diffuse inflammatory changes in the colonic mucosa, requires novel treatment method. Photodynamic therapy (PDT), as a promising physico-chemical treatment method, were used to treat UC rats’ model with novel photosensitizer LD4 in this paper, the treatment effect and mechanism was investigated. LD4-PDT could improve the survival rate of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced UC model rats, decrease expression of interleukin (IL)-6, IL-1, tumor necrosis factor (TNF)-α, malondialdehyde (MDA), myeloperoxidase (MPO) and increase the expression of glutathione (GSH) and superoxide oxidase (SOD), while protecting the integrity of the intestinal epithelium. LD4-PDT treatment could rebuild the intestinal microflora composition and reprogram the colonic protein profiles in TNBS-induced rats to almost the normal state. Proteomics analysis based upon TNBS-induced UC model rats revealed that Amine oxidase copper-containing 1 (AOC1) was a potential target of LD4-PDT. Novel photosensitizer agent LD4-PDT represents an efficient treatment method for UC, and AOC1 may be a promising target.

Acute kidney injury (AKI) is a common and serious complication of sepsis accompanied by kidney dysfunction resulting from various etiologies and pathophysiological processes. Unfortunately, there is currently no ideal therapeutic strategy for AKI. Numerous studies have confirmed that long noncoding RNAs (lncRNAs) play important regulatory roles in the pathogenesis of sepsis-associated AKI. In this study, lncRNA TCONS_00016406 (termed lncRNA 6406), a novel lncRNA identified by using TargetScan, was significantly downregulated in the kidney tissues of mice with sepsis-associated AKI. This study aimed to explore the role of lncRNA 6406 in lipopolysaccharide (LPS)-induced AKI and its potential molecular mechanism. The models of sepsis-induced AKI (called LPS-induced AKI models) in mice and cell lines were established with male C57BL/6 mice and renal tubular epithelial (PTEC) cells, respectively. Twenty-four hours after LPS administration, kidneys and cell samples were collected after various treatments to examine the alterations in the lncRNA 6406 levels and to evaluate the effects on LPS-induced inflammation, oxidative stress, and apoptosis through real-time PCR (RT-PCR) analysis, western blotting, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The results revealed that lncRNA 6406 could significantly attenuate LPS-induced AKI, as shown by the alleviation of inflammation, the suppression of oxidative stress and the inhibition of apoptosis. Mechanistically, a luciferase reporter assay and additional research showed that lncRNA 6406 functioned as a ceRNA to sponge miRNA-687, thereby modulating LPS-stimulated AKI by targeting the miR-687/PTEN axis; thus, this study presents a novel therapeutic strategy or sepsis-associated AKI.

Berberine (BBR) has a variety of pharmacological activities and is widely used in Asian countries. However, the clinical application of BBR still lacks scientific basis, what protective mechanism of BBR against myocardial ischemia-reperfusion injury (MIRI). In vitro experiments, BBR pretreatment regulated autophagy-related protein expression, induced cell proliferation and autophagosome formation, and reduced the mitochondrial membrane potential (ΔΨm) increase in H9C2 cells. In vivo experiments, BBR reduced the myocardial infarct size, decreased cardiomyocyte apoptosis, and markedly decreased myocardial enzyme (CK-MB, LDH, and AST) activity-induced I/R. In addition, upon BNIP3 knockdown, the regulatory effects of BBR on the above indicators were weakened both in H9C2 cells and in vivo. Luciferase reporter and ChIP assays indicated that BBR mediated BNIP3 expression by enhancing the binding of HIF-1α to the BNIP3 promoter. BBR protects against myocardial I/R injury by inducing cardiomyocytes proliferation, inhibiting cardiomyocytes apoptosis, and inducing the mitophagy-mediated HIF-1α/BNIP3 pathway. Thus, BBR may serve as a novel therapeutic drug for myocardial I/R injury.

Interferons (IFNs) establish dynamic host defense mechanisms by inducing various IFN-stimulated genes that encodes many antiviral innate immune effectors. IFN-inducible transmembrane (IFITM) proteins have been identified as intrinsic antiviral effectors, which block the entry of a broad spectrum of enveloped RNA viruses by interrupting virus-endosomal fusion. However, antiviral activity of IFITM proteins against mammalian DNA virus has not been demonstrated till date. Here, we sought to investigate the antiviral activities and mechanisms of interferon-inducible transmembrane protein 3 (IFITM3) protein against poxvirus infection. Analysis of expression kinetics of cell endogenous IFITM3 protein indicated that vaccinia virus (VACV) infection suppressed its translation, which was independent of IRF3 phosphorylation triggered by VACV. Although silencing of endogenous IFITM proteins did not affect their baseline antiviral effects in the cell, it has reduced the IFN-α-mediated inhibition of VACV infection, and also modulated VACV-induced cell death. Moreover, we discovered that overexpression of IFITM3 significantly restricted VACV infection, replication and proliferation mainly by interfering with virus entry processes prior to the virus nucleocapsid entry into the cytoplasm. Interestingly, IFITM3 overexpression showed an impact on virus binding. Furthermore, IFITM3 interfered with the cytosolic entry of virus through low pH-dependent fashion. Taken together, our findings provide the first evidence of exogenously expressed IFITM3 protein restricting infection of an enveloped DNA virus, thus expanding their antiviral spectrum. This study further explores the complex mechanism and provides novel insights into the interaction between virus infection and host defense.

BackgroundImmune checkpoint inhibitors (ICIs) have dramatically improved survival in advanced gastrointestinal (GI) cancer patients, but also resulted in immune-related adverse events (irAEs). This study aimed to evaluate serological biomarkers of irAEs and treatment response in GI cancer patients.Patients and methodsMetastatic GI cancer patients were enrolled between August 1, 2015, and July 31, 2017. Serum samples were collected at baseline, and a panel of 59 serum biomarkers was tested. The occurrence of irAEs was analyzed, and serological biomarker expression was correlated with irAE incidence and prognosis.ResultsFifty-one patients were enrolled, of whom 47.1% (24/51) were diagnosed with irAEs, including 4 patients (7.8%) with grade 3-5 irAEs. The most common irAE was thyroiditis (9/51, 17.6%), followed by colitis (7/51, 13.7%). The expression of CD28 (P = 0.042), IL-4 (P = 0.033), IL-15 (P = 0.024) and PD-L1 (P = 0.018) was significantly elevated in patients with grade 3-5 irAEs. For organ-specific irAEs, IL-6 levels were higher in patients with thyroiditis and colitis, while IL-22 and SCF levels were higher in patients with colitis. Increased IL-1α, IL-21, LIF, and PIGF-1 levels were significantly associated with myositis incidence, while the serum levels of six cytokines (BTLA, GM-CSF, IL-4, PD-1, PD-L1 and TIM-3) were higher in patients with rash. Prognostic analysis showed that patients with irAEs had better tumor response (P = 0.029), improved PFS (median survival: undefined vs. 2.1 months, P = 0.002), and extended OS (median survival: undefined vs. 4.3 months, P = 0.003). The prognostic value of irAEs was only significant in patients who received anti-PD-1 inhibitors, but not in those who received anti-PD-L1 inhibitors. Besides, elevated BTLA (median OS: not reached vs. 7 months; P = 0.0168) and PD-1 (median OS: not reached vs. 7 months; P = 0.0223) concentrations were associated with longer OS.ConclusionsSerological proteins are promising markers for predicting immune-related toxicity and prognosis in GI cancer patients. Organ-specific irAEs have various cytokine profiles. Although further validation is needed before clinical application, this study provided a direction for identifying patients at risk for irAEs, and guiding patient selection for ICI therapy.

To compare the gut microbiota of healthy infants based on specific interactions of delivery modes and feeding types, we recruited 62 healthy babies who were followed up for 2 years from our previous cohort study of 91 infants (the rest were lost to follow-up). They were exclusively fed breast milk or specific formulas for more than 4 months after birth. The fecal bacterial composition was tested at 40 days, 3 months, and 6 months of age. Solid foods were introduced from 4 to 6 months of age and thus did not affect the microbiota before 4 months of age. According to the different delivery modes (i.e., vaginal delivery, VD, or cesarean section delivery, CS) and feeding types (i.e., breast-fed, br, or formula-fed, fo), the infants were assigned to four different groups, namely, the VD-br, VD-fo, CS-br, and CS-fo groups. We found that at 40 days of age, the α diversity (reported as the Shannon index) was lower in the br infants than in the fo infants. At 3 months of age, the α diversity was significantly lower in the CS-br group, although significant differences were not observed after solid food introduction. Bifidobacterium represented the most predominant genus in all groups at all time points, followed by Enterobacteriaceae. At 40 days of age, the abundance of Bifidobacterium was much higher in the CS-br group than in the CS-fo group but did not differ between the VD-br and VD-fo groups. The differences in Bifidobacterium disappeared at 3 and 6 months of age among the different groups. At 40 days of age, the abundance of Streptococcus and Enterococcus was much lower in the br infants than in the CS-fo group. At 3 months of age, Enterococcus was significantly lower in the CS-br group than in the fo infants, although for infants delivered by VD, the difference between feeding types was not significant. The specific interaction of delivery modes and feeding types has a large impact on the infants' gut microbiota. Breastfeeding and VD may decrease the potential adverse effects of formula feeding or CS delivery on gut microbiota, thus leading to a more stable and beneficial gut environment for infants.

Working memory lies at the core of cognitive function and plays a crucial role in children's learning, reasoning, problem solving, and intellectual activity. Behavioral findings have suggested that acute aerobic exercise improves children's working memory; however, there is still very little knowledge about whether a single session of aerobic exercise can alter working memory's brain activation patterns, as assessed by functional magnetic resonance imaging (fMRI). Therefore, we investigated the effect of acute moderate-intensity aerobic exercise on working memory and its brain activation patterns in preadolescent children, and further explored the neural basis of acute aerobic exercise on working memory in these children. We used a within-subjects design with a counterbalanced order. Nine healthy, right-handed children were scanned with a Siemens MAGNETOM Trio 3.0 Tesla magnetic resonance imaging scanner while they performed a working memory task (N-back task), following a baseline session and a 30-min, moderate-intensity exercise session. Compared with the baseline session, acute moderate-intensity aerobic exercise benefitted performance in the N-back task, increasing brain activities of bilateral parietal cortices, left hippocampus, and the bilateral cerebellum. These data extend the current knowledge by indicating that acute aerobic exercise enhances children's working memory, and the neural basis may be related to changes in the working memory's brain activation patterns elicited by acute aerobic exercise. [ABSTRACT FROM AUTHOR]

Mycoplasma hominis, commonly residing in the genitourinary tract, can cause rare extragenital infections, especially in immunocompromised individuals. This report details a case of chronic osteomyelitis with a pathological femur fracture in a 79-year-old woman. Despite a history of bone tuberculosis, the infection was identified as Mycoplasma hominis through culture and mass spectrometry, highlighting the diagnostic challenges due to the organism’s lack of a cell wall. This case underscores the necessity for advanced diagnostic methods and awareness of Mycoplasma hominis in non-urogenital infections.

Drug addiction often correlates with criminal behavior. When investigating criminal behavior among individuals grappling with drug addiction, it becomes crucial to scrutinize the influence of dopamine. Substances such as heroin, morphine, methamphetamine and other drugs can cause abnormal dopamine secretion when people are addicted to them, which promotes changes in the brain’s reward circuit and emotional balance, thereby increasing susceptibility to criminal behavior. The pivotal role of dopamine within the reward pathway and its regulatory function in emotional processes exert profound influence on behavior following drug simulation. These influences are primarily manifested by three distinct attributes: a singular criminal motive and objective, lack of moral sense, and impulsive decision-making processes. Drawing upon the distinctive dopaminergic dynamics inherent in individuals afflicted by drug addiction, this study advocates for targeted corrective interventions. The preventive paradigm encompasses the cultivation of supportive community environments, the establishment of comprehensive databases, and providing legal education and protection, among other initiatives. In terms of treatment, along with judicial sanctions and protections, exercise regimens and psychotherapeutic interventions are advocated. The corrective endeavor necessitates a synergistic integration of community-based and legalistic frameworks. The objective is to furnish guiding principles for tackling criminal behavior precipitated by aberrant dopamine secretion, underpinned by a scientifically informed approach.

Both selenium (Se) and anthocyanins are crucial for maintaining human health. Preharvest Se treatments could promote anthocyanin biosynthesis and augment Se levels in vegetables, helping to combat Se deficiencies in dietary intake. However, it remains unknown whether preharvest Se treatment could balance growth and anthocyanin biosynthesis in plants and what the appropriate treatment concentration is. In this study, preharvest treatments with sodium selenite at varying concentrations (0, 5, 10, and 30 mg/kg) affect the growth and nutritional quality of purple leaf mustard (Brassica juncea) with abundant anthocyanins. Lower Se concentrations (≤10 mg/kg) of preharvest treatments enhanced photosynthesis, facilitated root system development, consequently elevated the biomass. Conversely, higher Se levels (≥30 mg/kg) reduced photosynthesis and biomass. The dosage-dependent effects of Se treatments were corroborated through seedlings cultivated in hydroponic conditions. Moreover, nearly all Se treatments elevated the contents of various nutrients in leaf mustard, particularly anthocyanin and organic se. These results suggest an overall enhancement in nutritional quality of leaf mustard plants. Furthermore, the application of 10 mg/kg Se significantly enhanced the activity of phenylalanine ammonia-lyase and upregulated the expression of 12 genes pivotal for anthocyanin biosynthesis, further demonstrating the fortified effects of Se enrichment on anthocyanins in leaf mustard. Low-level Se treatments resulted in heightened antioxidant activity (APX, CAT, and POD), mitigating reactive oxygen species induced by increasing Se content in tissues. The enhanced antioxidant activities may be beneficial for the normal growth of leaf mustard under Se stress conditions. In conclusion, our study demonstrated preharvest Se treatment at 10 mg/kg could balance the growth and anthocyanin biosynthesis in purple leaf mustard. This study offers valuable insights into anthocyanin fortification through Se enrichment methods in agricultural practices, ensuring that such fortification does not compromise leafy vegetable yield.

The broad spectrum of intellectual disability (ID) patients’ clinical manifestations, the heterogeneity of ID genetic variation, and the diversity of the phenotypic variation represent major challenges for ID diagnosis. By exploiting a manually curated systematic phenotyping cohort of 3803 patients harboring ID, we identified 704 pathogenic genes, 3848 pathogenic sites, and 2075 standard phenotypes for underlying molecular perturbations and their phenotypic impact. We found the positive correlation between the number of phenotypes and that of patients that revealed their extreme heterogeneities, and the relative contribution of multiple determinants to the heterogeneity of ID phenotypes. Nevertheless, despite the extreme heterogeneity in phenotypes, the ID genes had a specific bias of mutation types, and the top 44 genes that ranked by the number of patients accounted for 39.9% of total patients. More interesting, enriched co-occurrent phenotypes and co-occurrent phenotype networks for each gene had the potential for prioritizing ID genes, further exhibited the convergences of ID phenotypes. Then we established a predictor called IDpred using machine learning methods for ID pathogenic genes prediction. Using10-fold cross-validation, our evaluation shows remarkable AUC values for IDpred (auc = 0.978), demonstrating the robustness and reliability of our tool. Besides, we built the most comprehensive database of ID phenotyped cohort to date: IDminer http://218.4.234.74:3100/IDminer/, which included the curated ID data and integrated IDpred tool for both clinical and experimental researchers. The IDminer serves as an important resource and user-friendly interface to help researchers investigate ID data, and provide important implications for the diagnosis and pathogenesis of developmental disorders of cognition.