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Oxidative stress is an important contributor to the pathogenesis of Alzheimer’s disease (AD). The overproduction of reactive oxygen species observed in AD patients results in the loss of mitochondrial function, altered metal ion homeostasis, lipopolysaccharide metabolism disorder, reduced anti-oxidant defense, increased release of inflammatory factors, and the aggravation and accumulation of amyloid-beta and tau hyper-phosphorylation, which directly cause synaptic and neuronal loss and lead to cognitive dysfunction. Thus, oxidative stress proves to be a fundamental part of AD development and progression, suggesting the potential benefits of anti-oxidant-based therapies for AD. In this study, we found that a water-soluble extract of Artemisia annua (WSEAA), a traditional Chinese herbal medicine, has a strong anti-oxidant function. We also found that WSEAA is able to improve the cognitive function of 3xTg AD mice. However, the mechanisms and molecular targets underlying WSEAA action are still not known. In order to uncover the potential molecular mechanisms involved, we used a combination of network pharmacology and different experimental approaches. Obtained results revealed key genes (such as AKT1, BCL2, IL-6, TNF-[Formula: see text] and BAX) and signaling pathways (like PI3K-AKT and BCL2/BAX) are closely associated with the biological processes responding to oxidative stress. Further verification of the survival/anti-oxidant effects of WSEAA in vitro and in vivo showed that the extract has anti-oxidatant/neuronal survival action against H2O2-induced damage, and is thus able to prevent the cognitive decline and pathological changes of 3xTg transgenic (3xTg) mice via the regulation of key target-genes and pathways, such as PI3K-AKT and BCL2/BAX, related to survival/apoptosis. Our findings strongly indicate the potential of WSEAA for the prevention and treatment of AD.

Here, we report a novel route to construct efficient thin-film perovskite solar cells from sintering of nanocrystals and a facile two-step sintering process is proposed to achieve precise control over the microstructure development.

Although young people want to know more about sexuality, they do not feel they have received what they need to learn. In Chinese societies, scant research has solicited direct input from the youth to obtain their views on sexuality education (SE) deliverables. We found research gaps in the lack of Chinese preteens' input regarding SE timing, knowledge perception, learning readiness, and preteens' reasons for obtaining information about sexual health. In Hong Kong, a not-for-profit agency collected data from Chinese preadolescents who expressed opinions through a general survey. This agency surveyed students from 24 primary schools and provided anonymous secondary data for this team to analyze further. Among 4569 fifth- and sixth-grade students (average 11 years old), girls were more likely than boys to seek sex-related information from teachers, library books, and mothers. In contrast, boys were more likely than girls to obtain information from friends, pornographic comics, and the internet. Logistic regression analysis indicated that gender, age, instructional sources, openness to sexual health knowledge, and perceived and actual levels of knowledge predicted preteens' desire to receive SE earlier in grade school. Girls and older students were significantly more likely to report their preference to receive SE in an earlier grade. We recommend that preteens and their parents be encouraged to collaborate with teachers to participate in school-based SE programming.

Porous hydrogel dressings show breathability and possibility to carry and release basic fibroblast growth factor (bFGF) to promote wound healing. However, the difficult replacement may lead to the secondary damage. Thus, there is an urgent need to develop a method platform to control the degradation rate of hydrogel, so as to realize the on-demand replacement. The present study fabricated a porous hydrogel from co-polymized N,N′-bis(acryloyl) cystamine (BAC), allyl polyethylene glycol 500 (APEG500) and acrylic acid (AA) with the presence of polycaprolactone (PCL). BAC contains disulfide bond, which crosslinked the hydrogel. The pore size of the porous hydrogel was 400–600 μm. Higher content of BAC indicated higher crosslinking density, which reduced swelling ratio of hydrogel, while promoted hydrogel storage modulus. At the same time, the presence of PCL reduced swelling ratio of hydrogel, while promoted hydrogel mechanical properties, endowing hydrogel with tough feature. Porous hydrogels that crosslinked by disulfide bonds immersed in glutathione solution were found to degrade spontaneously and quickly due to the response to glutathione. Both crosslinking density and PCL content affected the degradation rate. The porous hydrogel carrying bFGF was applied to wound, promoting angiogenesis, thus accelerating wound healing within 12 d. Due to the spontaneous and rapid degradation of optimized porous hydrogel on wound within 3 days, there was no operation of removing dressing during treatment, avoiding damage during dressing replacement.

In recent years, alterations in lipid metabolism are currently considered a hallmark feature of many diseases. However, the role in women with reproductive dysfunction (WRD) remains to be fully elucidated. Here, this study aimed to explore the effect of lipid metabolism-related genes (LMRGs) on endometrial receptivity of WRD.This study retrospectively analyzed endometrial receptivity array (ERA) in GEO database. The differential expression genes (DEGs) were obtained by limma differential analysis, and the core genes and corresponding predicted microRNA were obtained through protein-protein interaction (PPI) analysis and TargetScan database, so as to predict the chemical targets of drug therapy. Through the intersection of DEGs and LMRGs, the target gene expression profile was obtained for subsequent consensus clustering analysis and immune analysis. In addition, the immune cell infiltration was assessed by applying the ESTIMATE and MCPcounter algorithm and potential drug targets were obtained from the HERB website.1473 genes showed differential expression between the groups of WRD and fertile women, and then a large number of lipid metabolism-related pathways and immune-related pathways were enriched. Twelve core genes and corresponding predicted miR-134-3p were obtained; most importantly, we found that these 12 genes were all LMRGs. Through drug target prediction, we obtained three drugs that regulate lipid metabolism and improve blood circulation, namely lovastatin, estrogen, and quercetin. EHHADH (AUC = 0.85) and PTEN (AUC = 0.82) have the best diagnostic performance. UMAP and heatmap revealed large differences between three clusters. LMRGs revealed specific manifestations of WRD in endometrial receptivity and immune microenvironment.Our study explored the expression pattern of LMRGs in endometrium of WRD, screened the corresponding biomarkers, and proposed the combination of traditional Chinese and Western medicine to improve the endometrial receptivity.

We aim to explore the effect of head-down position (HDP), initiated within 24 hours of onset, in moderate anterior circulation stroke patients with probable large artery atherosclerosis (LAA) etiology. This investigator-initiated, multi-center trial prospective, randomized, open-label, blinded-endpoint, multi-center and phase-2 trial was conducted in China and completed in 2021. Eligible patients were randomly assigned (1:1) into the HDP group receiving −20° Trendelenburg, or control group receiving standard care according to national guideline. The primary endpoint was proportion of modified Rankin Scale (mRS) of 0 to 2 at 90 days, which is a scale for measuring the degree of disability after stroke. 90-day mRS was assessed by a certified staff member who was blinded to group assignment. A total of 96 patients were randomized (47 in HDP group and 49 in control group) and 94 (97.9%) patients were included in the final analysis: 46 in HDP group and 48 in control group. The proportion of favorable outcome was 65.2% (30/46) in the HDP group versus 50.0% (24/48) in the control group (unadjusted: OR 2.05 [95%CI 0.87-4.82], P = 0.099). No severe adverse event was attributed to HDP procedures. This work suggests that the head-down position seems safe and feasible, but does not improve favorable functional outcome in acute moderate stroke patients with LAA. This trial was registered with ClinicalTrials.gov, NCT03744533.

Relapsed or refractory (r/r) mantle cell lymphoma (MCL) is an aggressive B-cell malignancy with poor prognosis. Bruton's tyrosine kinase (BTK) is a mediator of B-cell receptor signaling and is associated with the development of B-cell lymphomas. Patients with r/r MCL were enrolled in this phase 1/2 study and treated with orelabrutinib, a novel, highly selective BTK inhibitor. The median number of prior regimens was two (range, 1 to 4). The median age was 62 years (range, 37 to 73 years). Eligible patients received oral orelabrutinib 150 mg once daily (n = 86) or 100 mg twice daily (n = 20) until disease progression or unacceptable toxicity. 150 mg once daily was chosen as the preferred RP2D. After a median follow-up of 23.8 months, the overall response rate was 81.1%, with 27.4% achieving complete response and 53.8% achieving partial response. The median duration of response and progression-free survival were 22.9 and 22.0 months, respectively. The median overall survival (OS) was not reached and the rate of OS at 24 months was 74.3%. Adverse events (AE) occurring in > 20% of patients were thrombocytopenia (34.0%), upper respiratory tract infection (27.4%), and neutropenia (24.5%). Grade ≥ 3 AE were infrequent and most commonly included thrombocytopenia (13.2%), neutropenia (8.5%), and anemia (7.5%). Three patients discontinued treatment due to treatment-related adverse events (TRAE) and no fatal TRAE were reported. Orelabrutinib showed substantial efficacy and was well tolerated in patients with r/r MCL. This trial was registered at www.clinicaltrials.gov as #NCT03494179.

Table S1: Enzymatic activities of SKLB261 against recombinant human protein kinases. Table S2: IC50 values (microM) for inhibition of cell growth after treatment with SKLB261, gemcitabine, erlotinib, dasatinib, or sunitinib for 72 h. Table S3: Pharmacokinetic parameters for SKLB261 in Sprague−Dawley rats. Table S4: Analysis of statistical significance of animal survival after treatment with SKLB261 or other agents. Figure S1: Growth inhibition of pancreatic tumor cell lines after treatment with SKLB261, dasatinib, gemcitabine, erlotinib, or sunitinib. Figure S2: The effect of SKLB261 treatment on tumor weight and body weight of mice with human pancreatic tumor xenografts. Figure S3: Antitumor efficacy of SKLB261 in PANC-1 tumor xenografts. Figure S4: Effect of SKLB261 on tumor angiogenesis in vivo. Figure S5: The effect of SKLB261 on tumor angiogenesis after treatment for 3 days or 5 days. Figure S6: Anti-metastatic activities of SKLB261 against pancreatic cancer cells in vitro.

Previous studies have suggested that a low albumin-to-alkaline phosphatase ratio (AAPR) is associated with a lower survival rate in patients with various malignancies. However, the relationship between pretreatment AAPR and the prognosis of patients with gastric cancer (GC) remains unclear.To investigate the prognostic value of AAPR in distant metastatic GC.A total of 191 patients with distant metastatic cancer from a single institute were enrolled in this study. Pretreatment clinical data, including serum albumin and alkaline phosphatase levels, were collected. A chi-square test or Fisher's exact test was applied to evaluate the correlations between AAPR and various clinical parameters in GC patients. The Kaplan-Meier method and Cox proportional hazards regression model were used to evaluate the prognostic efficacy of AAPR in metastatic GC patients. A two-sidedA receiver operating characteristic curve indicated that 0.48 was the optimal threshold value for AAPR. AAPR ≤ 0.48 was significantly associated with bone (Pretreatment AAPR may serve as an independent prognostic factor for predicting PFS and OS in patients with metastatic GC. Furthermore, AAPR may assist clinicians with individualizing treatment.

A low-power wideband self-biased phase-locked loop (SPLL) is proposed for multi-protocol SerDes applications in this letter. With the proposed adaptive fast-locking current circuit (AFLCC), the settling time is reduced significantly, and no extra power and jitter contribution. In addition, a start-up module is adopted to reset the system to an optimal initial operating frequency quickly. The proposed 1-3-GHz SPLL, fabricated in TSMC 28-nm CMOS process and occupies a compact 0.028mm2 area. It achieves a roughly constant settling time of 5 μs over all frequencies and division ratios range. Only 0.96 mW is consumed from a 0.9 V supply at 1 GHz frequency.

This letter presents a 1-3GHz low-power, fast-locking self-biased phase-locked loop (SPLL) for multiprotocol SerDes applications. The PLL realizes adaptive bandwidth tracking based on fast-locking current injection, which accelerates loop acquisition and maintains reduced settling time across a wide frequency range. Additionally, a start-up module is adopted to reset the system quickly to an optimal initial operating frequency. The proposed PLL, fabricated in TSMC 28-nm CMOS process and occupies a compact 0.028mm2 area. It achieves a roughly constant settling time of 5 μs over all frequencies and division ratios range. Compared with the typical SPLL, the measured settling time can be shortened about 85% large division ratios.

This paper aims to analyze the influence of laptop brand image on the purchasing intention of Chinese college students, and it further looks at the moderating role played by consumer ethnocentrism in the above causality, which helps to bridge the research gap in the domain. Employing the brand image theory and consumer ethnocentrism theory, and based on large-sample questionnaire surveys, this study reveals that brand image positively affects college students' purchasing intention of laptops, regardless of domestic or foreign laptop brands. What is more, besides playing a direct role in affecting purchasing intention, consumer ethnocentrism also plays a significant moderating role in affecting the effects of brand image on purchasing intention. It is found that high ethnocentric college students may not buy foreign laptops, even though the brand image of foreign laptops is superior. Overall, this paper has made important suggestions and implications for both corporate managers and policy makers.