Electrochemical splitting of water provides an attractive way to produce hydrogen fuel. Unfortunately, the efficient and large-scale H2 production is still hindered by the sluggish kinetics of the ...oxygen evolution reaction (OER) at the anode side of a water electrolyzer. Starting from metal-organic frameworks (MOFs), we demonstrate a template-engaged strategy to transform Ni-Ni Prussian blue analogue (PBA) nanoplates into porous carbon coated nickel phosphides nanoplates with mixed phases of Ni5P4 and Ni2P. For comparison, NiO and Ni(OH)2 porous nanoplates with the similar morphology have also been synthesized from the same precursor. Benefitting from their structural merits and the in situ formed catalytically active oxidized nickel species, the as-derived nickel phosphides manifest excellent electrocatalytic activity for OER superior to NiO and Ni(OH)2.
Background and Purpose
Atopic dermatitis is a common chronic pruritic inflammatory disease of the skin involving neuro‐immune communication. Neuronal mechanism‐based therapeutic treatments remain ...lacking. We investigated the efficacy of intravenous lidocaine therapy on atopic dermatitis and the underlying neuro‐immune mechanism.
Experimental Approach
Pharmacological intervention, immunofluorescence, RNA‐sequencing, genetic modification and immunoassay were performed to dissect the neuro‐immune basis of itch and inflammation in atopic dermatitis‐like mouse model and in patients.
Key Results
Lidocaine alleviated skin lesions and itch in both atopic dermatitis patients and calcipotriol (MC903)‐induced atopic dermatitis model by blocking subpopulation of sensory neurons. QX‐314, a charged NaV blocker that enters through pathologically activated large‐pore ion channels and selectivity inhibits a subpopulation of sensory neurons, has the same effects as lidocaine in atopic dermatitis model. Genetic silencing NaV1.8‐expressing sensory neurons was sufficient to restrict cutaneous inflammation and itch in the atopic dermatitis model. However, pharmacological blockade of TRPV1‐positive nociceptors only abolished persistent itch but did not affect skin inflammation in the atopic dermatitis model, indicating a difference between sensory neuronal modulation of skin inflammation and itch. Inhibition of activity‐dependent release of calcitonin gene‐related peptide (CGRP) from sensory neurons by lidocaine largely accounts for the therapeutic effect of lidocaine in the atopic dermatitis model.
Conclusion and Implications
NaV1.8+ sensory neurons play a critical role in pathogenesis of atopic dermatitis and lidocaine is a potential anti‐inflammatory and anti‐pruritic agent for atopic dermatitis. A dissociable difference for sensory neuronal modulation of skin inflammation and itch contributes to further understanding of pathogenesis in atopic dermatitis.
The novel coronavirus disease (COVID-19) pandemic remains a global public health crisis, presenting a broad range of challenges. To help address some of the main problems, the scientific community ...has designed vaccines, diagnostic tools and therapeutics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The rapid pace of technology development, especially with regard to vaccines, represents a stunning and historic scientific achievement. Nevertheless, many challenges remain to be overcome, such as improving vaccine and drug treatment efficacies for emergent mutant strains of SARS-CoV-2. Outbreaks of more infectious variants continue to diminish the utility of available vaccines and drugs. Thus, the effectiveness of vaccines and drugs against the most current variants is a primary consideration in the continual analyses of clinical data that supports updated regulatory decisions. The first two vaccines granted Emergency Use Authorizations (EUAs), BNT162b2 and mRNA-1273, still show more than 60% protection efficacy against the most widespread current SARS-CoV-2 variant, Omicron. This variant carries more than 30 mutations in the spike protein, which has largely abrogated the neutralizing effects of therapeutic antibodies. Fortunately, some neutralizing antibodies and antiviral COVID-19 drugs treatments have shown continued clinical benefits. In this review, we provide a framework for understanding the ongoing development efforts for different types of vaccines and therapeutics, including small molecule and antibody drugs. The ripple effects of newly emergent variants, including updates to vaccines and drug repurposing efforts, are summarized. In addition, we summarize the clinical trials supporting the development and distribution of vaccines, small molecule drugs, and therapeutic antibodies with broad-spectrum activity against SARS-CoV-2 strains.
Abstract
Background
The R1441G mutation in the leucine-rich repeat kinase 2 (LRRK2) gene results in late-onset Parkinson’s disease (PD). Peripheral inflammation and gut microbiota are closely ...associated with the pathogenesis of PD. Chronic periodontitis is a common type of peripheral inflammation, which is associated with PD.
Porphyromonas gingivalis
(Pg), the most common bacterium causing chronic periodontitis, can cause alteration of gut microbiota. It is not known whether Pg-induced dysbiosis plays a role in the pathophysiology of PD.
Methods
In this study, live Pg were orally administrated to animals, three times a week for 1 month. Pg-derived lipopolysaccharide (LPS) was used to stimulate mononuclear cells in vitro. The effects of oral Pg administration on the gut and brain were evaluated through behaviors, morphology, and cytokine expression.
Results
Dopaminergic neurons in the substantia nigra were reduced, and activated microglial cells were increased in R1441G mice given oral Pg. In addition, an increase in mRNA expression of tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β) as well as protein level of α-synuclein together with a decrease in zonula occludens-1 (Zo-1) was detected in the colon in Pg-treated R1441G mice. Furthermore, serum interleukin-17A (IL-17A) and brain IL-17 receptor A (IL-17RA) were increased in Pg-treated R1441G mice.
Conclusions
These findings suggest that oral Pg-induced inflammation may play an important role in the pathophysiology of LRRK2-associated PD.
The waste shrimp shells (SS) were used as both carbon and nitrogen sources to directly synthesize N and P co-doped carbon networks with abundant mesopores and high specific surface area by simple ...acid pretreatment and carbonization. Using exogenous phosphorus as dopant, the prepared catalyst (PA-SS 900) favorably possessed a high oxygen reduction reaction (ORR) activity regarding half-wave potential (0.82 V) and limiting current (4.47 mA cm−2), which approached those of commercial 20 wt% Pt/C. For practical application in microbial fuel cell (MFC), the N, P co-doped PA-SS 900 achieved a maximum power density (MPD) of 802 mW m−2 and an open circuit voltage (OCV) of 653 mV, which also were close to that (892 mW m−2 and 752 mV) based on 20% Pt/C as cathode catalyst. Remarkably, the synthetic catalyst had a better long-term stability than that of 20% Pt/C in alkaline medium. These results demonstrated that N, P co-doped PA-SS 900 was an accessible and efficient ORR catalyst in air-cathode MFC for relatively desirable energy generation and wastewater treatment. Further, the direct utilization of waste shrimp shells replacing chitin or chitosan in energy conversion is worthy of in-depth study due to the advantages of simple process, environmental friendliness and availability.
The waste shrimp shells were used as both carbon and nitrogen source to directly synthesize efficient ORR catalyst for MFCs. Display omitted
•Shrimp shells as nitrogen source were directly used to prepare ORR catalysts.•Removing CaCO3 and in-situ pore in shrimp shells promoted the active sites.•Hydrothermal process with phosphoric acid facilitated similar spherical carbon.•N, P co-doped carbon exhibited good ORR property, stability and application in MFC.
Background
Current guidelines recommend oral anticoagulation (OAC) following transcatheter aortic valve replacement (TAVR) in patients with clinical indication, but the optimal antithrombotic regimen ...remains uncertain. We aimed to compare the efficacy and safety of non‐vitamin K oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in patients undergoing TAVR with concomitant indication of OAC.
Hypothesis
Comparing with VKAs therapy, NOACs are similar in reducing the all‐cause mortality and major bleeding in post‐TAVR patients requiring OAC medication.
Methods
We searched the databases of PubMed, Embase, and Cochrane library databases to identify studies that investigated NOACs versus VKAs after TAVR in patients with another indication of OAC, which were published before 28th September 28, 2021. The effectiveness of outcomes was all‐cause mortality and stroke or systemic embolism, while the main safety outcome was major and/or life‐threatening bleeding. The hazard ratio (HR) with 95% confidence interval (CI) was used as a measure of treatment effect.
Results
Our search identified eight studies. We included 4947 post‐TAVR patients with another indication of OAC allocated to the NOAC (n = 2146) or VKA groups (n = 2801). There were no significant differences in the all‐cause mortality (HR: 0.91, 95% CI: 0.77–1.08, p = .29, I2 = 47%), stroke or systemic embolism (HR: 0.96, 95% CI: 0.68–1.37, p = .84, I2 = 0%), and major and/or life‐threatening bleeding (HR: 1.09, 95% CI: 0.89–1.32, p = .40, I2 = 30%) in both groups.
Conclusion
Among post‐TAVR patients who required OAC therapy, NOACs therapy compared to VKAs is similar in reducing the all‐cause mortality, stroke or systemic embolism, and major and/or life‐threatening bleeding events.
Aim
Up‐to‐date epidemiological studies on the global burden of severe periodontitis is scarce. This study aimed to present the latest estimates for prevalence of severe periodontitis from 1990 to ...2019, by region, age, and level of socio‐demographic development.
Materials and Methods
Estimates from the Global Burden of Disease study 2019 were used to investigate burden and trends of prevalence of severe periodontitis and its association with socio‐demographic development at global, regional, and national level. Decomposition analysis was performed to explore the contribution of demographic and epidemiological factors to the evolving burden of severe periodontitis.
Results
In 2019, there were 1.1 billion (95% uncertainty interval: 0.8–1.4 billion) prevalent cases of severe periodontitis globally. From 1990 to 2019, age‐standardized prevalence rate of severe periodontitis increased by 8.44% (6.62%–10.59%) worldwide. Prevalence of severe periodontitis is higher among less developed countries/regions. Global population growth accounted for 67.9% of the increase in the number of prevalent cases of severe periodontitis from 1990 to 2019.
Conclusions
The global burden of severe periodontitis has been substantial and increasing over the past three decades. Upstream policy changes are urgently needed to address the global public health challenge of severe periodontitis.
Abstract A cross-sectional study design was applied amongst a random sample (n = 10158) of Chinese adolescents. Self-completed questionnaires, including demographic characteristics, Internet use ...situation, Youth Internet Addiction Test, Youth Social Support Rating Scale and Zung Self-rating Depression Scale were utilized to examine the study objectives. Among the study population, the prevalence rate of Internet addiction was 10.4%, with 1038 (10.2%) moderately and 21 (0.2%) severely addicted to the Internet. Results from the multivariate logistic regression analyses suggested that a variety of related factors have significant effects on Internet addiction (parental control, per capita annual household income, academic performance, the access to Internet, online activities). The correlation coefficients showed that Internet addiction was negatively correlated with social support and positively associated with depression. Social support had a significant negative predictive effect on Internet addiction. The mediating effect of depression between social support and Internet addiction was remarkable.
Hepatocellular carcinoma (HCC) is considered one of the most common cancers, characterized by low early detection and high mortality rates, and is a global health challenge. Immunogenic cell death ...(ICD) is defined as a specific type of regulated cell death (RCD) capable of reshaping the tumor immune microenvironment by releasing danger signals that trigger immune responses, which would contribute to immunotherapy.
The ICD gene sets were collected from the literature. We collected expression data and clinical information from public databases for the HCC samples in our study. Data processing and mapping were performed using R software to analyze the differences in biological characteristics between different subgroups. The expression of the ICD representative gene in clinical specimens was assessed by immunohistochemistry, and the role of the representative gene in HCC was evaluated by various in vitro assays, including qRT-PCR, colony formation, and CCK8 assay. Lasso-Cox regression was used to screen prognosis-related genes, and an ICD-related risk model (ICDRM) was constructed. To improve the clinical value of ICDRM, Nomograms and calibration curves were created to predict survival probabilities. Finally, the critical gene of ICDRM was further investigated through pan-cancer analysis and single-cell analysis.
We identified two ICD clusters that differed significantly in terms of survival, biological function, and immune infiltration. As well as assessing the immune microenvironment of tumors in HCC patients, we demonstrate that ICDRM can differentiate ICD clusters and predict the prognosis and effectiveness of therapy. High-risk subpopulations are characterized by high TMB, suppressed immunity, and poor survival and response to immunotherapy, whereas the opposite is true for low-risk subpopulations.
This study reveals the potential impact of ICDRM on the tumor microenvironment (TME), immune infiltration, and prognosis of HCC patients, but also a potential tool for predicting prognosis.
Intrahepatic cholangiocarcinoma (ICC) is characterized by its dense fibrotic microenvironment and highly malignant nature, which are associated with chemotherapy resistance and very poor prognosis. ...Although circRNAs have emerged as important regulators in cancer biology, their role in ICC remains largely unclear. Herein, a circular RNA, cPKM is identified, which is upregulated in ICC and associated with poor prognosis. Silencing cPKM in ICC cells reduces TGFB1 release and stromal fibrosis, inhibits STMN1 expression, and suppresses ICC growth and metastasis, moreover, it also leads to overcoming paclitaxel resistance. This is regulated by the interactions of cPKM with miR-199a-5p or IGF2BP2 and by the ability of cPKM to stabilize STMN1/TGFB1 mRNA. Based on these findings, a Trojan horse nanotherapy strategy with co-loading of siRNA against cPKM (si-cPKM) and paclitaxel (PTX) is developed. The siRNA/PTX co-loaded nanosystem (Trojan horse) efficiently penetrates tumor tissues, releases si-cPKM and paclitaxel (soldiers), promotes paclitaxel sensitization, and suppresses ICC proliferation and metastasis in vivo. Furthermore, it alleviates the fibrosis of ICC tumor stroma and reopens collapsed tumor vessels (opening the gates), thus enhancing the efficacy of the standard chemotherapy regimen (main force). This novel nanotherapy provides a promising new strategy for ICC treatment.
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