Academic resilience refers to the ability to recover and achieve high academic outcomes despite environmental adversity in the academic setting. At the same time, self-determination theory (SDT) ...offers a human agency model to understand individuals' autonomy to achieve in various fields. The present longitudinal study explored the factors influencing resilience from the analytical framework of SDT to investigate how basic psychological needs strengthen students' resilience. A mediation model was proposed that resilience may mediate the relationship between basic psychological needs and academic performance. The results from 450 10th grade Chinese students showed that three basic psychological needs (i.e., autonomy, competence, and relatedness) facilitate academic resilience; academic resilience thus increases subsequent academic performance after controlling for previous test scores.
Abstract Inhibition of mTOR by rapamycin has been shown to suppress seizures in TSC/PTEN genetic models. Rapamycin, when applied immediately before or after a neurological insult, also prevents the ...development of spontaneous recurrent seizures (epileptogenesis) in an acquired model. In the present study, we examined the mTOR pathway in rats that had already developed chronic spontaneous seizures in a pilocarpine model. We found that mTOR is aberrantly activated in brain tissues from rats with chronic seizures. Furthermore, inhibition of mTOR by rapamycin treatment significantly reduces seizure activity. Finally, mTOR inhibition also significantly suppresses mossy fiber sprouting. Our findings suggest the possibility for a much broader window for intervention for some acquired epilepsies by targeting the mTOR pathway.
Certain mutations within the mammalian target of rapamycin (mTOR) pathway, most notably those affecting the tuberous sclerosis complex (TSC), lead to aberrant activation of mTOR and result in a high ...incidence of epilepsy in humans and animal models. Although hyperactivation of mTOR has been strongly linked to the development of epilepsy and, conversely, inhibition of mTOR by rapamycin treatment is protective against seizures in several models, the downstream epileptic mechanisms have remained elusive. Autophagy, a catabolic process that plays a vital role in cellular homeostasis by mediating the turnover of cytoplasmic constituents, is negatively regulated by mTOR. Here we demonstrate that autophagy is suppressed in brain tissues of forebrain-specific conditional TSC1 and phosphatase and tensin homlog knock-out mice, both of which display aberrant mTOR activation and seizures. In addition, we also discovered that autophagy is suppressed in the brains of human TSC patients. Moreover, conditional deletion of Atg7, an essential regulator of autophagy, in mouse forebrain neurons is sufficient to promote development of spontaneous seizures. Thus, our study suggests that impaired autophagy contributes to epileptogenesis, which may be of interest as a potential therapeutic target for epilepsy treatment and/or prevention.
•COVID-19 caused by SARS-CoV-2 has become a global pandemic•Clinical characteristics assessed for 22 neonates born to mothers with COVID-19 during pregnancy•COVID-19 in the third trimester of ...pregnancy could cause fetal kidney developmental injury•There is the possibility of maternal-fetal transmission of SARS-CoV-2•Study provides a theoretical basis for early diagnosis of developmental toxicity in neonates from mothers with COVID-19
Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic. However, the hazard to newborns in pregnancy remains controversial. The aim of this study was to investigate the vertical transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from mother to child and developmental toxicity in the fetus.
All clinical information was recorded on 22 neonates born to mothers with confirmed COVID-19 pneumonia in Tongji Hospital.
The average birth weight of the 22 newborns (16 males and 6 females) was 2980 g, and the mean gestational week was 37W+3. The birth weight of three babies was <2500 g, and the gestational week of all three low-birth-weight neonates was less than 36W. Three newborns had minor lesions of infection in the lungs as shown by computed tomography (CT) scans. Furthermore, three newborns had elevated SARS-CoV-2-related immunoglobin M (IgM) antibodies, and 11 newborns (52.4%) had positive immunoglobin G (IgG) antibodies. Notably, both cystatin C and β2-microglobulin were increased in all newborns. Five of the 21 tested newborns had leukocytosis, and 11 had increased neutrophil levels. In addition, the aspartate aminotransferase of 18 newborns and the γ-glutamyl transpeptidase of 19 newborns were increased. Total bilirubin was elevated in all newborns and serum albumin was reduced in 20 of 22 newborns.
This study was the first to discover that COVID-19 infection in the third trimester of pregnancy could cause fetal kidney developmental injury, as indicated by increased cystatin C and β2-microglobulin in all neonates. Furthermore, there is the possibility of maternal-fetal transmission of SARS-CoV-2.
Owing to the generation of waste during mining and processing, granite stone causes great damage to the environment. In this study, the broken granite waste and the stone powder were used as concrete ...coarse aggregate and “admixture” to make granite waste concrete hollow blocks, which could meet the requirements of compressive strength, durability and economy. The influence of the water-binder ratio, cement dosage, and powder-slag ratio on the compressive strength and freeze-thaw properties of the block were analyzed. Subsequently, the optimal mix ratio was determined based on range analysis. The effect of granite waste on the compressive strength and durability of the blocks was also analyzed. In addition, the economic effects of the granite waste concrete hollow block were analyzed. The results show that granite waste concrete hollow blocks with a water-binder ratio of 0.55, powder slag ratio of 15%, and cement dosages of 340 kg/m3 and 320 kg/m3 can meet the strength requirements of MU10 grade and the requirements of freeze-thaw properties. The strength and frost resistance of the granite concrete hollow blocks were enhanced because the granite powder filled the aggregate gaps. In addition, the price of granite concrete hollow blocks was reduced by approximately 50%. The small hollow block of granite concrete is environmentally friendly and worth promoting.
Abstract
The persistent pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants accentuates the great demand for ...developing effective therapeutic agents. Here, we report the development of an orally bioavailable SARS-CoV-2 3C-like protease (3CL
pro
) inhibitor, namely simnotrelvir, and its preclinical evaluation, which lay the foundation for clinical trials studies as well as the conditional approval of simnotrelvir in combination with ritonavir for the treatment of COVID-19. The structure-based optimization of boceprevir, an approved HCV protease inhibitor, leads to identification of simnotrelvir that covalently inhibits SARS-CoV-2 3CL
pro
with an enthalpy-driven thermodynamic binding signature. Multiple enzymatic assays reveal that simnotrelvir is a potent pan-CoV 3CL
pro
inhibitor but has high selectivity. It effectively blocks replications of SARS-CoV-2 variants in cell-based assays and exhibits good pharmacokinetic and safety profiles in male and female rats and monkeys, leading to robust oral efficacy in a male mouse model of SARS-CoV-2 Delta infection in which it not only significantly reduces lung viral loads but also eliminates the virus from brains. The discovery of simnotrelvir thereby highlights the utility of structure-based development of marked protease inhibitors for providing a small molecule therapeutic effectively combatting human coronaviruses.
Lung cancer is the leading cause of cancer-related mortality globally. Discovering effective biomarkers for early diagnosis and prognosis is important to reduce the mortality rate and ensure ...efficient therapy for lung cancer patients. C-type lectin domain family 3 member B (CLEC3B) has been reported in various cancers, but its correlation with lung cancer remains elusive.
The GEO, TCGA and Oncomine databases were analyzed to examine the expression of CLEC3B in lung cancer. The CLEC3B mRNA levels in 15 patient tissue samples were detected by real-time PCR and the CLEC3B protein levels in 34 patient tissue samples were detected by immunohistochemistry. A Chi-square test was performed to analyze the correlation of CLEC3B expression and clinicopathological factors. The diagnostic value of CLEC3B was revealed by receiver operating characteristic (ROC) curves. Univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier plots were used to evaluate the prognostic value of CLEC3B in lung cancer. The TIMER database was used to evaluate the correlation of CLEC3B and immune infiltration. Gene set enrichment analysis revealed tumor-associated biological processes related to CLEC3B.
CLEC3B is significantly downregulated in lung cancer patients compared with nontumor controls according to database analysis and patient tissue sample detection (p < 0.001). Specifically, CLEC3B is significantly downregulated in stage IA lung cancer patients (p < 0.001) and has a high diagnostic accuracy (area under the receiver operating characteristic curve > 0.9). Moreover, low expression of CLEC3B is related to poor progression-free survival (HR = 0.60, 95% CI 0.49-0.74, p = 8.3e-07) and overall survival (HR = 0.66, 95% CI 0.58-0.75, p = 2.1e-10), indicating it as a risk factor for lung cancer. Multivariate analysis value showed that low expression of CLEC3B may be an independent risk factor for disease-free survival in lung cancer patients (HR = 0.655, 95% CI 0.430-0.996, Cox p = 0.048). In addition, we also investigated the potential role of CLEC3B in tumor-immune interactions and found that CLEC3B might be associated with the immune infiltration and immune activation of lung cancer, especially in squamous cell carcinoma.
Our findings indicate that CLEC3B expression is downregulated in lung cancer and reveal the diagnostic and prognostic potential of CLEC3B in lung cancer and its potential as an immune-related therapeutic target in lung cancer.
Introduction
Community‐acquired pneumonia (CAP) is the major cause of infection‐related mortality worldwide. Patients with CAP frequently present with admission hyperglycemia.
Objectives
The aim of ...this study was to evaluate the association between admission blood glucose (ABG) level and clinical outcomes in elderly CAP patients (≥80 years of age) with or without diabetes.
Methods
In this single center retrospective study, 290 elderly patients diagnosed with CAP were included. Demographic and clinical information were collected and compared. The associations between admission blood glucose level and the 30‐day mortality as well as intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) in elderly CAP patients with or without diabetes were assessed.
Results
Of the 290 eligible patients with CAP, 159 (66.5%) patients were male, and 64 (22.1%) had a known history of diabetes at hospital admission. After adjusting for age and sex, the logistic regression analysis had identified several risk factors that might be associated with clinical outcomes in elderly patients with CAP. Multivariable logistic regression analysis revealed that admission glucose level > 11.1 mmol/L was significant associated with ICU admission, IMV, and 30‐day mortality both in non‐diabetic and diabetic patients. Furthermore, Kaplan–Meier analysis indicated that patients with higher admission glucose level were correlated statistically significantly with 30‐day mortality in patients with CAP (P < 0.001).
Conclusion
Admission blood glucose is correlated with 30‐day hospital mortality, ICU admission, and IMV of CAP in elderly patients with and without diabetes. Specially, admission glucose > 11.1 mmol/L was a significant risk factor for 30‐day hospital mortality.
This study aimed to investigate the association between admission blood glucose level and clinical outcomes, including 30‐day mortality, ICU admission, and invasive mechanical ventilation, in elderly CAP patients with or without diabetes. The results showed that higher admission blood glucose is correlated with 30‐day hospital mortality, ICU admission, and IMV of elderly CAP patients with and without diabetes. Specially, admission glucose > 11.1 mmol/L were correlated statistically significantly with 30‐day hospital mortality in elderly CAP patients.
harbors a dipeptide (Dpp) transporter consisting of a substrate-binding protein (DppA), two permeases (DppB and C), and two ATPases (DppD and F). The Dpp transporter is responsible for the ...transportation of dipeptides and short peptides. We found that its expression is important for the growth of
.
. To understand the role of the Dpp transporter in the pathogenesis of
.
, the expression of virulence factors and
.
-induced IL-8 production were investigated in
wild-type and isogenic
Dpp transporter mutants. We found that expression of CagA was downregulated, while expression of type 4 secretion system (T4SS) components was upregulated in Dpp transporter mutants. The DppA mutant strain expressed higher levels of outer membrane proteins (OMPs), including BabA, HopZ, OipA, and SabA, and showed a higher adhesion level to gastric epithelial AGS cells compared with the
.
26695 wild-type strain. After infection of AGS cells,
.
Δ
induced a higher level of NF-κB activation and IL-8 production compared with wild-type. These results suggested that in addition to supporting the growth of
.
, the Dpp transporter causes bacteria to alter the expression of virulence factors and reduces
.
-induced NF-κB activation and IL-8 production in gastric epithelial cells.
Eliciting broad tier 2 neutralizing antibodies (nAbs) is a major goal of HIV-1 vaccine research. Here we investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit nAbs. ...Unusually potent nAb titers developed in 2 of 8 rabbits immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and in 1 of 20 rabbits immunized with DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. Specifically, trimer VLP sera took advantage of the unusual absence of a glycan at residue 197 (present in 98.7% of Envs). Intriguingly, removing the N197 glycan (with no loss of tier 2 phenotype) rendered 50% or 16.7% (n = 18) of clade B tier 2 isolates sensitive to the two trimer VLP sera, showing broad neutralization via the surface masked by the N197 glycan. Neutralizing sera targeted epitopes that overlap with the CD4 binding site, consistent with the role of the N197 glycan in a putative "glycan fence" that limits access to this region. A bioinformatics analysis suggested shared features of one of the trimer VLP sera and monoclonal antibody PG9, consistent with its trimer-dependency. The neutralizing DNA trimer serum took advantage of the absence of a glycan at residue 230, also proximal to the CD4 binding site and suggesting an epitope similar to that of monoclonal antibody 8ANC195, albeit lacking tier 2 breadth. Taken together, our data show for the first time that strain-specific holes in the glycan fence can allow the development of tier 2 neutralizing antibodies to native spikes. Moreover, cross-neutralization can occur in the absence of protecting glycan. Overall, our observations provide new insights that may inform the future development of a neutralizing antibody vaccine.
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