timsTOF HT Improves Protein Identification and Quantitative Reproducibility for Deep Unbiased Plasma Protein Biomarker Discovery.

Mass spectrometry (MS) is a valuable tool for plasma proteome profiling and disease biomarker discovery. However, wide-ranging plasma protein concentrations, along with technical and biological variabilities, present significant challenges for deep and reproducible protein quantitation. Here, we evaluated the qualitative and quantitative performance of timsTOF HT and timsTOF Pro 2 mass spectrometers for analysis of neat plasma samples (unfractionated) and plasma samples processed using the Proteograph Product Suite (Proteograph) that enables robust deep proteomics sampling prior to mass spectrometry. Samples were evaluated across a wide range of peptide loading masses and liquid chromatography (LC) gradients. We observed up to a 76% increase in total plasma peptide precursors identified and a >2-fold boost in quantifiable plasma peptide precursors (CV < 20%) with timsTOF HT compared to Pro 2. Additionally, approximately 4.5 fold more plasma peptide precursors were detected by both timsTOF HT and timsTOF Pro 2 in the Proteograph analyzed plasma vs neat plasma. In an exploratory analysis of 20 late-stage lung cancer and 20 control plasma samples with the Proteograph, which were expected to exhibit distinct proteomes, an approximate 50% increase in total and statistically significant plasma peptide precursors (q < 0.05) was observed with timsTOF HT compared to Pro 2. Our data demonstrate the superior performance of timsTOF HT for identifying and quantifying differences between biologically diverse samples, allowing for improved disease biomarker discovery in large cohort studies. Moreover, researchers can leverage data sets from this study to optimize their liquid chromatography-mass spectrometry (LC-MS) workflows for plasma protein profiling and biomarker discovery. (ProteomeXchange identifier: PXD047854 and PXD047839).

Risk of COVID-19 death for people with a pre-existing cancer diagnosis prior to COVID-19-vaccination: A systematic review and meta-analysis.

While previous reviews found a positive association between pre-existing cancer diagnosis and COVID-19-related death, most early studies did not distinguish long-term cancer survivors from those recently diagnosed/treated, nor adjust for important confounders including age. We aimed to consolidate higher-quality evidence on risk of COVID-19-related death for people with recent/active cancer (compared to people without) in the pre-COVID-19-vaccination period. We searched the WHO COVID-19 Global Research Database (20 December 2021), and Medline and Embase (10 May 2023). We included studies adjusting for age and sex, and providing details of cancer status. Risk-of-bias assessment was based on the Newcastle-Ottawa Scale. Pooled adjusted odds or risk ratios (aORs, aRRs) or hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated using generic inverse-variance random-effects models. Random-effects meta-regressions were used to assess associations between effect estimates and time since cancer diagnosis/treatment. Of 23 773 unique title/abstract records, 39 studies were eligible for inclusion (2 low, 17 moderate, 20 high risk of bias). Risk of COVID-19-related death was higher for people with active or recently diagnosed/treated cancer (general population: aOR = 1.48, 95% CI: 1.36-1.61, I2 = 0; people with COVID-19: aOR = 1.58, 95% CI: 1.41-1.77, I2 = 0.58; inpatients with COVID-19: aOR = 1.66, 95% CI: 1.34-2.06, I2 = 0.98). Risks were more elevated for lung (general population: aOR = 3.4, 95% CI: 2.4-4.7) and hematological cancers (general population: aOR = 2.13, 95% CI: 1.68-2.68, I2 = 0.43), and for metastatic cancers. Meta-regression suggested risk of COVID-19-related death decreased with time since diagnosis/treatment, for example, for any/solid cancers, fitted aOR = 1.55 (95% CI: 1.37-1.75) at 1 year and aOR = 0.98 (95% CI: 0.80-1.20) at 5 years post-cancer diagnosis/treatment. In conclusion, before COVID-19-vaccination, risk of COVID-19-related death was higher for people with recent cancer, with risk depending on cancer type and time since diagnosis/treatment.

Confidence sets for a level set in linear regression.

Regression modeling is the workhorse of statistics and there is a vast literature on estimation of the regression function. It has been realized in recent years that in regression analysis the ultimate aim may be the estimation of a level set of the regression function, ie, the set of covariate values for which the regression function exceeds a predefined level, instead of the estimation of the regression function itself. The published work on estimation of the level set has thus far focused mainly on nonparametric regression, especially on point estimation. In this article, the construction of confidence sets for the level set of linear regression is considered. In particular, 1 - α $$ 1-\alpha $$ level upper, lower and two-sided confidence sets are constructed for the normal-error linear regression. It is shown that these confidence sets can be easily constructed from the corresponding 1 - α $$ 1-\alpha $$ level simultaneous confidence bands. It is also pointed out that the construction method is readily applicable to other parametric regression models where the mean response depends on a linear predictor through a monotonic link function, which include generalized linear models, linear mixed models and generalized linear mixed models. Therefore, the method proposed in this article is widely applicable. Simulation studies with both linear and generalized linear models are conducted to assess the method and real examples are used to illustrate the method.

Enhancing mechanical properties of composite solid electrolyte by ultra-high molecular weight polymers.

Composite solid electrolytes combining the advantages of inorganic and polymer electrolytes are considered as one of the promising candidates for solid-state lithium metal batteries. Compared with ceramic-in-polymer electrolyte, polymer-in-ceramic electrolyte displays excellent mechanical strength to inhibit lithium dendrite. However, polymer-in-ceramic electrolyte faces the challenges of lack of flexibility and severely blocked Li+transport. In this study, we prepared polymer-in-ceramic film utilizing ultra-high molecular weight polymers and ceramic particles to combine flexibility and mechanical strength. Meanwhile, the ionic conductivity of polymer-in-ceramic electrolytes was improved by adding excess lithium salt in polymer matrix to form polymer-in-salt structure. The obtained film shows high stiffness (10.5 MPa), acceptable ionic conductivity (0.18 mS cm-1) and high flexibility. As a result, the corresponding lithium symmetric cell stably cycles over 800 h and the corresponding LiFePO4cell provides a discharge capacity of 147.7 mAh g-1at 0.1 C without obvious capacity decay after 145 cycles.

Synthesizing high performance LNMO cathode materials with porous structure by manipulating reynolds number in a microreactor.

The demand for Lithium-ion batteries (LIBs) has significantly grown in the last decade due to their extensive use electric vehicles. To further advance the commercialization of LIBs for various applications, there is a pressing need to develop electrode materials with enhanced performance. The porous microsphere morphology LiNixMn2-xO4(LNMO) is considered to be an effective material with both high energy density and excellent rate performance. Nevertheless, LNMO synthesis technology still has problem such as long reaction time, high energy consumption and environmental pollution. Herein, LNMO microsphere was successfully synthesized with short precursors reaction time (18 s) at 40 °C without using chelating agent by microreaction technology combined solid-state lithiation. The optimized LNMO cathode shows microsphere (∼8µm) morphology stacked by nano primary particles, with abundant mesoporous and fully exposed low-energy plane. The electrochemical analysis indicates that the optimized LNMO cathode demonstrates 97.33% capacity retention even after 200 cycles at 1C. Additionally, the material shows a highly satisfactory discharge capacity of 92.3 mAh·g-1at 10C. Overall, microreaction technology is anticipated to offer a novel approach in the synthesis of LNMO cathode materials with excellent performance.

Extraction of Dibenzyl Disulfide from Transformer Oils by Acidic Ionic Liquid.

In recent years, dibenzyl disulfide (DBDS) in transformer oils has caused many transformer failures around the world, and its removal has attracted more attention. In this work, nine imidazolium-based ionic liquids (ILs) were applied as effective, green desulfurization extractants for DBDS-containing transformer oil for the first time. The results show that the desulfurization ability of the ILs for DBDS followed the order of [BMIM]FeCl4 > [BMIM]N(CN)2 > [BMIM]SCN > [BMIM](C4H9O)2PO2 > [BMIM]MeSO4 > [BMIM]NTf2 > [BMIM]OTf > [BMIM]PF6 > [BMIM]BF4. Especially, [BMIM]FeCl4 ionic liquid had excellent removal efficiency for DBDS, with its S partition coefficient KN (S) being up to 2642, which was much higher than the other eight imidazolium-based ILs. Moreover, the extractive performance of [BMIM]FeCl4 increased with an increasing molar ratio of FeCl3 to [BMIM]Cl, which was attributed to its Lewis acidity and fluidity. [BMIM]FeCl4 ionic liquid could also avail in the desulfurization of diphenyl sulfide (DPS) from model oils. The experimental results demonstrate that π-π action, π-complexation, and Lewis acid-base interaction played important roles in the desulfurization process. Finally, the ([BMIM]FeCl4) ionic liquid could be recycled five times without a significant decrease in extractive ability.

Lymphocyte disturbance and functional assessment of the [Asp521Asn] ZAP70 mutation.

Activated zeta-chain-associated protein kinase 70 (ZAP70) phosphorylates the TCRαß:CD3:zeta complex to diversify and amplify TCR signaling. Patients with ZAP70 mutations can present with phenotypes of immune dysregulation as well as infection. We identified the first Taiwanese boy with the [Asp521Asn] ZAP70 mutation who presented with recurrent pneumonia, inflammatory bowel disease-like diarrhea, transient hematuria and autoimmune hepatitis. He had isolated CD8 lymphopenia, eosinophilia, hypogammaglobulinemia, and impaired lymphocyte proliferation. Downstream CD3/CD28 signaling, phosphorylation of AKT, ZAP70 and Ca2+ influx were decreased in [Asp521Asn] ZAP70 lymphocytes. Immunophenotyping analysis revealed expansion of transitional B and CD21-low B cells, Th2-skewing T follicular helper cells, but lower Treg cells. The Asp521Asn-ZAP70 hindered TCR-CD3 downstream phosphorylation and disturbed lymphocyte subgroup "profiles" leading to autoimmunity/autoinflammation. Further large-scale studies are warranted to clarify this lymphocyte disturbance. The prognosis significantly depends on hematopoietic stem cell transplantation, but not the genotype, the presence of opportunistic infections or immune dysregulation.

GO-CoNiP New Composite Material Modified Separator for Long Cycle Lithium-Sulfur Batteries.

Lithium-sulfur batteries with high capacity are considered the most promising candidates for next-generation energy storage systems. Mitigating the shuttle reaction and promoting catalytic conversion within the battery are major challenges in the development of high-performance lithium-sulfur batteries. To solve these problems, a novel composite material GO-CoNiP is synthesized in this study. The material has excellent conductivity and abundant active sites to adsorb polysulfides and improve reaction kinetics within the battery. The initial capacity of the GO-CoNiP separator battery at 1 C is 889.4 mAh g-1 , and the single-cycle decay is 0.063% after 1000 cycles. In the 4 C high-rate test, the single-cycle decay is only 0.068% after 400 cycles. The initial capacity is as high as 828.2 mAh g-1 under high sulfur loading (7.3 mg cm-2 ). In addition, high and low-temperature performance tests are performed on the GO-CoNiP separator battery. The first cycle discharge reaches 810.9 mAh g-1 at a low temperature of 0 °C, and the first cycle discharge reaches 1064.8 mAh g-1 at a high temperature of 60 °C, and both can run stably for 120 cycles. In addition, in situ Raman tests are conducted to explain the adsorption of polysulfides by GO-CoNiP from a deeper level.

One-year review of real-time artificial intelligence (AI)-aided endoscopy performance.

BACKGROUND: Colonoscopies have long been the gold standard for detection of pre-malignant neoplastic lesions of the colon. Our previous study tried real-time artificial intelligence (AI)-aided colonoscopy over a three-month period and found significant improvements in collective and individual endoscopist's adenoma detection rates compared to baseline. As an expansion, this study evaluates the 1-year performance of AI-aided colonoscopy in the same institution. METHODS: A prospective cohort study was conducted in a single institution in Singapore. The AI software used was GI Genius™ Intelligent Endoscopy Module, US-DG-2000309 © 2021 Medtronic. Between July 2021 and June 2022, polypectomy rates in non-AI-aided colonoscopies and AI-aided colonoscopies were calculated and compared. Some of the AI-aided colonoscopies were recorded and video reviewed. A "hit" was defined as a sustained detection of an area by the AI. If a polypectomy was performed for a "hit," its histology was reviewed. Additional calculations for polyp detection rate (PDR), adenoma detection rate (ADR), and adenoma detection per colonoscopy (ADPC) were performed. Cost analysis was performed to determine cost effectiveness of subscription to the AI program. RESULTS: 2433 AI-aided colonoscopies were performed between July 2021 and June 2022 and compared against 1770 non-AI-aided colonoscopies. AI-aided colonoscopies yielded significantly higher rates of polypectomies (33.6%) as compared with non-AI-aided colonoscopies (28.4%) (p < 0.001). Among the AI-aided colonoscopies, 1050 were reviewed and a final 843 were included for additional analysis. The polypectomy to "hit" ratio was 57.4%, PDR = 45.6%, ADR = 32.4%, and ADPC = 2.08. Histological review showed that 25 polyps (3.13%) were sessile-serrated adenomas. Cost analysis found that the increased polypectomy rates in AI-aided colonoscopes led to an increase in revenue, which covered the subscription cost with an excess of USD 20,000. CONCLUSION: AI-aided colonoscopy is a cost effective means of improving colonoscopy quality and may help advance colorectal cancer screening in Singapore.

Pre-operative erector spinae plane block should be considered a viable option for laparoscopic colectomies.

BACKGROUND: The Erector Spinae Plane (ESP) block is a recent development in the field of regional anaesthesia and has been increasingly explored for abdominal surgeries to reduce opioid use and improve pain control. Colorectal cancer is the commonest cancer in multi-ethnic Singapore and requires surgery for curative treatment. ESP is a promising alternative in colorectal surgeries, but few studies have evaluated its efficacy in such surgeries. Therefore, this study aims to evaluate the use of ESP blocks in laparoscopic colorectal surgeries to establish its safety and efficacy in this field. METHODS: A prospective two-armed interventional cohort study comparing T8-T10 ESP blocks with conventional multimodal intravenous analgesia for laparoscopic colectomies was conducted in a single institution in Singapore. The decision for doing an ESP block versus conventional multimodal intravenous analgesia was made by a consensus between the attending surgeon and anesthesiologist. Outcomes measured were total intra-operative opioid consumption, post-operative pain control and patient outcome. Post-operative pain control was measured by pain score, analgesia use, and amount of opioids consumed. Patient outcome was determined by presence of ileus. RESULTS: A total of 146 patients were included, of which 30 patients received an ESP block. Overall, the ESP group had a significantly lower median opioid usage both intra-operatively and post-operatively (p = 0.031). Fewer patients required patient-controlled analgesia and rescue analgesia post-operatively for pain control (p < 0.001) amongst the ESP group. Pain scores were similar and post-operative ileus was absent in both groups. Multivariate analysis found that the ESP block had an independent effect on reducing intra-opioid consumption (p = 0.014). Multivariate analysis of post-operative opioid use and pain scores did not yield statistically significant results. CONCLUSIONS: The ESP block was an effective alternative regional anaesthesia for colorectal surgery that reduced intra-operative and post-operative opioid use while attaining satisfactory pain control.

Preoperative prediction of extrathyroidal extension: radiomics signature based on multimodal ultrasound to papillary thyroid carcinoma.

BACKGROUND: There is a recognized need for additional approaches to improve the accuracy of extrathyroidal extension (ETE) diagnosis in papillary thyroid carcinoma (PTC) before surgery. Up to now, multimodal ultrasound has been widely applied in disease diagnosis. We investigated the value of radiomic features extracted from multimodal ultrasound in the preoperative prediction of ETE. METHODS: We retrospectively pathologically confirmed PTC lesions in 235 patients from January 2019 to April 2022 in our hospital, including 45 ETE lesions and 205 non-ETE lesions. MaZda software was employed to obtain radiomics parameters in multimodal sonography. The most valuable radiomics features were selected by the Fisher coefficient, mutual information, probability of classification error and average correlation coefficient methods (F + MI + PA) in combination with the least absolute shrinkage and selection operator (LASSO) method. Finally, the multimodal model was developed by incorporating the clinical records and radiomics features through fivefold cross-validation with a linear support vector machine algorithm. The predictive performance was evaluated by sensitivity, specificity, accuracy, F1 scores and the area under the receiver operating characteristic curve (AUC) in the training and test sets. RESULTS: A total of 5972 radiomics features were extracted from multimodal sonography, and the 13 most valuable radiomics features were selected from the training set using the F + MI + PA method combined with LASSO regression. The multimodal prediction model yielded AUCs of 0.911 (95% CI 0.866-0.957) and 0.716 (95% CI 0.522-0.910) in the cross-validation and test sets, respectively. The multimodal model and radiomics model showed good discrimination between ETE and non-ETE lesions. CONCLUSION: Radiomics features based on multimodal ultrasonography could play a promising role in detecting ETE before surgery.

Polyphyllin VII induces autophagy-dependent ferroptosis in human gastric cancer through targeting T-lymphokine-activated killer cell-originated protein kinase.

T-lymphokine-activated killer cell-originated protein kinase (TOPK) is a serine-threonine kinase that is overexpressed in gastric cancer (GC) and promotes tumor progression. Polyphyllin VII (PPVII), a pennogenin isolated from the rhizomes of Paris polyphylla, shows anticancer effects. Here, we explored the antitumor activity and mechanism of PPVII in GC. Ferroptosis was detected by transmission electron microscope, malondialdehyde, and iron determination assays. Autophagy and its upstream signaling pathway were detected by Western blot, and gene alterations. The binding of PPVII and TOPK was examined through microscale thermophoresis and drug affinity responsive target stability assays. An in vivo mouse model was performed to evaluate the therapeutic of PPVII. PPVII inhibits GC by inducing autophagy-mediated ferroptosis. PPVII promotes the degradation of ferritin heavy chain 1, which is responsible for autophagy-mediated ferroptosis. PPVII activates the Unc-51-like autophagy-activating kinase 1 (ULK1) upstream of autophagy. PPVII inhibits the activity of TOPK, thereby weakening the inhibition of downstream ULK1. PPVII stabilizes the dimer of the inactive form of TOPK by direct binding. PPVII inhibits tumor growth without causing obvious toxicity in vivo. Collectively, this study suggests that PPVII is a potential agent for the treatment of GC by targeting TOPK to activate autophagy-mediated ferroptosis.

LSD-YOLOv5: A Steel Strip Surface Defect Detection Algorithm Based on Lightweight Network and Enhanced Feature Fusion Mode.

In the field of metallurgy, the timely and accurate detection of surface defects on metallic materials is a crucial quality control task. However, current defect detection approaches face challenges with large model parameters and low detection rates. To address these issues, this paper proposes a lightweight recognition model for surface damage on steel strips, named LSD-YOLOv5. First, we design a shallow feature enhancement module to replace the first Conv structure in the backbone network. Second, the Coordinate Attention mechanism is introduced into the MobileNetV2 bottleneck structure to maintain the lightweight nature of the model. Then, we propose a smaller bidirectional feature pyramid network (BiFPN-S) and combine it with Concat operation for efficient bidirectional cross-scale connectivity and weighted feature fusion. Finally, the Soft-DIoU-NMS algorithm is employed to enhance the recognition efficiency in scenarios where targets overlap. Compared with the original YOLOv5s, the LSD-YOLOv5 model achieves a reduction of 61.5% in model parameters and a 28.7% improvement in detection speed, while improving recognition accuracy by 2.4%. This demonstrates that the model achieves an optimal balance between detection accuracy and speed, while maintaining a lightweight structure.

HDAC1: An Essential and Conserved Member of the Diverse Zn2+-Dependent HDAC Family Driven by Divergent Selection Pressure.

Zn2+-dependent histone deacetylases (HDACs) are enzymes that regulate gene expression by removing acetyl groups from histone proteins. These enzymes are essential in all living systems, playing key roles in cancer treatment and as potential pesticide targets. Previous phylogenetic analyses of HDAC in certain species have been published. However, their classification and evolutionary origins across biological kingdoms remain unclear, which limits our understanding of them. In this study, we collected the HDAC sequences from 1451 organisms and performed analyses. The HDACs are found to diverge into three classes and seven subclasses under divergent selection pressure. Most subclasses show species specificity, indicating that HDACs have evolved with high plasticity and diversification to adapt to different environmental conditions in different species. In contrast, HDAC1 and HDAC3, belonging to the oldest class, are conserved and crucial in major kingdoms of life, especially HDAC1. These findings lay the groundwork for the future application of HDACs.

Research Progress on Skin Aging and Active Ingredients.

With the advancement of living standards in modern society and the emergence of an aging population, an increasing number of people are becoming interested in the topic of aging and anti-aging. An important feature of aging is skin aging, and women are particularly concerned about skin aging. In the field of cosmetics, the market share of anti-aging products is increasing year by year. This article reviews the research and development progress of skin aging and related active compounds both domestically and internationally in recent years. The results show that, in terms of the research on skin aging, the popular theories mainly include free radicals and oxidative stress theory, inflammation theory, photoaging theory, and nonenzymatic glycosyl chemistry theory. In terms of research on the active ingredients with anti-aging activities in the skin, there are numerous reports on related products in clinical studies on human subjects, animal experiments, and experimental studies on cell cultures, with a variety of types. Most of the compounds against skin aging are sourced from natural products and their action mechanisms are mainly related to scavenging oxygen free radicals and enhancing antioxidant defenses. This review provides important references for the future research of skin aging and the development of related products. Although there is a great progress in skin aging including related active ingredients, ideal compounds or products are still lacking and need to be further validated. New mechanisms of skin aging, new active ingredients sourced from natural and artificial products, and new pharmaceutical forms including further clinical validations should be further investigated in the future.

Antibacterial Activity and Mechanism of Canagliflozin against Methicillin-Resistant Staphylococcus aureus.

Diabetic foot infection (DFI) is a common complication in diabetes patients, with foot infections being the leading cause of amputations. Staphylococcus aureus is frequently found in diabetic foot infections, of which methicillin-resistant Staphylococcus aureus (MRSA) has become a major clinical and epidemiological challenge. Since MRSA strains are resistant to most ß-lactam antibiotics, and also partially resistant to other antibiotics, treatment is difficult and costly. The emergence of drug-resistant bacteria often arises from overuse or misuse of antibiotics. Clinically, canagliflozin is commonly used for the treatment of type 2 diabetes. On this basis, we investigated the antibacterial activity and mechanism of canagliflozin against MRSA, with the aim to discover novel functions of canagliflozin and provide new insights for the treatment of MRSA. Using the microbroth dilution method to determine the half maximal inhibitory concentration of drugs, we found that canagliflozin not only can inhibit the growth of methicillin-sensitive Staphylococcus aureus (MSSA) but also exhibits antibacterial activity against MRSA. The IC50 values, at approximately 56.01 µM and 57.60 µM, were almost the same. At 12 h, canagliflozin showed a significant antibacterial effect against MRSA at and above 30 µM. In addition, its combined use with penicillin achieved better antibacterial effects, which were increased by about three times. Additive antibacterial activity (FICI = 0.69) was found between penicillin and canagliflozin, which was better than that of doxycycline and canagliflozin (FICI = 0.95). Canagliflozin also affected bacterial metabolic markers, such as glucose, ATP, and lactic acid. The results of crystal violet staining indicate that canagliflozin disrupted the formation of bacterial biofilm. Our electron microscopy results showed that canagliflozin distorted the bacterial cell wall. The results of RT-PCR suggest that canagliflozin down-regulated the expressions of biofilm-related gene (clfA, cna, agrC, mgrA, hld) and methicillin-resistance gene (mecA), which was related to MRSA. Molecular docking also indicated that canagliflozin affected some interesting targets of MRSA, such as the sarA, crtM and fnbA proteins. In conclusion, canagliflozin exhibits antibacterial activity against MRSA by affecting bacterial metabolism, inhibiting its biofilm formation, distorting the bacterial cell wall, and altering the gene expression of biofilm formation and its virulence. Our study reveals the antibacterial activity of canagliflozin against MRSA, providing a new reference for treating diabetic foot infections.

Improving Low-temperature Performance and Stability of Na2 Ti6 O13 Anodes by the Ti-O Spring Effect through Nb-doping.

Na2 Ti6 O13 (NTO) with high safety has been regarded as a promising anode candidate for sodium-ion batteries. In the present study, integrated modification of migration channels broadening, charge density re-distribution, and oxygen vacancies regulation are realized in case of Nb-doping and have obtained significantly enhanced cycling performance with 92 % reversible capacity retained after 3000 cycles at 3000 mA g-1 . Moreover, unexpected low-temperature performance with a high discharge capacity of 143 mAh g-1 at 100 mA g-1 under -15 °C is also achieved in the full cell. Theoretical investigation suggests that Nb preferentially replaces Ti3 sites, which effectively improves structural stability and lowers the diffusion energy barrier. What's more important, both the in situ X-ray diffraction (XRD) and in situ Raman furtherly confirm the robust spring effect of the Ti-O bond, making special charge compensation mechanism and respective regulation strategy to conquer the sluggish transport kinetics and low conductivity, which plays a key role in promoting electrochemical performance.

[Efficacy of intramuscular injection of Xiyanping injection for the treatment of acute bronchitis in children: a multicenter, randomized, parallel-controlled clinical study]. / å–œç‚Žå¹³æ³¨å°„æ¶²è‚Œå† æ³¨å°„æ²»ç–—å°å„¿æ€¥æ€§æ”¯æ°”ç®¡ç‚Žçš„ç–—æ•ˆï¼šä¸€é¡¹å¤šä¸­å¿ƒã€éšæœºã€å¹³è¡Œå¯¹ç §ä¸´åºŠç ”ç©¶.

OBJECTIVES: To study the efficacy and safety of Xiyanping injection through intramuscular injection for the treatment of acute bronchitis in children. METHODS: A prospective study was conducted from December 2021 to October 2022, including 78 children with acute bronchitis from three hospitals using a multicenter, randomized, parallel-controlled design. The participants were divided into a test group (conventional treatment plus Xiyanping injection; n=36) and a control group (conventional treatment alone; n=37) in a 1:1 ratio. Xiyanping injection was administered at a dose of 0.3 mL/(kg·d) (total daily dose ≤8 mL), twice daily via intramuscular injection, with a treatment duration of ≤4 days and a follow-up period of 7 days. The treatment efficacy and safety were compared between the two groups. RESULTS: The total effective rate on the 3rd day after treatment in the test group was significantly higher than that in the control group (P<0.05), while there was no significant difference in the total effective rate on the 5th day between the two groups (P>0.05). The rates of fever relief, cough relief, and lung rale relief in the test group on the 3rd day after treatment were higher than those in the control group (P<0.05). The cough relief rate on the 5th day after treatment in the test group was higher than that in the control group (P<0.05), while there was no significant difference in the fever relief rate and lung rale relief rate between the two groups (P>0.05). The cough relief time, daily cough relief time, and nocturnal cough relief time in the test group were significantly shorter than those in the control group (P<0.05), while there were no significant differences in the fever duration and lung rale relief time between the two groups (P>0.05). There was no significant difference in the incidence of adverse events between the two groups (P>0.05). CONCLUSIONS: The overall efficacy of combined routine treatment with intramuscular injection of Xiyanping injection in the treatment of acute bronchitis in children is superior to that of routine treatment alone, without an increase in the incidence of adverse reactions.

The circadian clock protein Rev-erbα provides neuroprotection and attenuates neuroinflammation against Parkinson's disease via the microglial NLRP3 inflammasome.

BACKGROUND: Circadian disturbance is a common nonmotor complaint in Parkinson's disease (PD). The molecular basis underlying circadian rhythm in PD is poorly understood. Neuroinflammation has been identified as a key contributor to PD pathology. In this study, we explored the potential link between the core clock molecule Rev-erbα and the microglia-mediated NLR family pyrin domain-containing 3 (NLRP3) inflammasome in PD pathogenesis. METHODS: We first examined the diurnal Rev-erbα rhythms and diurnal changes in microglia-mediated inflammatory cytokines expression in the SN of MPTP-induced PD mice. Further, we used BV2 cell to investigate the impacts of Rev-erbα on NLRP3 inflammasome and microglial polarization induced by 1-methyl-4-phenylpyridinium (MPP+) and αsyn pre-formed fibril. The role of Rev-erbα in regulating microglial activation via NF-κB and NLRP3 inflammasome pathway was then explored. Effects of SR9009 against NLRP3 inflammasome activation, microgliosis and nigrostriatal dopaminergic degeneration in the SN and striatum of MPTP-induced PD mice were studied in detail. RESULTS: BV2 cell-based experiments revealed the role of Rev-erbα in regulating microglial activation and polarization through the NF-κB and NLRP3 inflammasome pathways. Circadian oscillation of the core clock gene Rev-erbα in the substantia nigra (SN) disappeared in MPTP-induced PD mice, as well as diurnal changes in microglial morphology. The expression of inflammatory cytokines in SN of the MPTP-induced mice were significantly elevated. Furthermore, dopaminergic neurons loss in the nigrostriatal system were partially reversed by SR9009, a selective Rev-erbα agonist. In addition, SR9009 effectively reduced the MPTP-induced glial activation, microglial polarization and NLRP3 inflammasome activation in the nigrostriatal system. CONCLUSIONS: These observations suggest that the circadian clock protein Rev-erbα plays an essential role in attenuating neuroinflammation in PD pathology, and provides a potential therapeutic target for PD treatment.

Zika virus infection induced apoptosis by modulating the recruitment and activation of pro-apoptotic protein Bax.

Zika virus (ZIKV) infection is associated with microcephaly in newborns and serious neurological complications in adults. Apoptosis of neural progenitor cells induced by ZIKV infection is believed to be a main reason for ZIKV infection-related microcephaly. However, the detailed mechanism of ZIKV infection-induced apoptosis remains to be elucidated. In this report, ZIKV infection induced the conformational activation of the pro-apoptotic protein Bax, with subsequent formation of oligomers of Bax in the mitochondria. Cell apoptosis was reduced significantly in SY5Y cells subjected to Bax knockdown. Additionally, while decreasing Bax expression inhibited the release of Cyt c from the mitochondria and reduced the rate of loss of mitochondrial membrane potential induced by ZIKV infection, silencing Bak, caspase-8, and/or caspase-10 expression did not. Mitochondria isolated from the untreated ZIKV-infected cells displayed Bax-binding ability and the subsequent release of Cyt c. This study also indicated that the NS4B protein of ZIKV recruited Bax to the mitochondria and induced Bax conformational activation. The overexpressed NS4B was localized to the mitochondria and induced cell apoptosis by activating the pro-apoptotic protein Bax. All the above results indicated that ZIKV infection directly impacted the mitochondrial apoptotic pathway by modulating the recruitment and activation of Bax.Importance: Since the large outbreaks that occurred in the Pacific Islands and Latin America in 2013, Zika virus has been confirmed a neuroteratogenic pathogen and causative agent of microcephaly and other developmental anomalies of the central nervous system in children born to infected mothers. As the widespread apoptosis throughout the whole brain, studies in animal models have reinforced the link between microcephaly caused by ZIKV infection and NPC apoptosis. Currently, the detailed mechanism of ZIKV infection-induced apoptosis still remains to be elucidated. Here, we firstly demonstrate that ZIKV infection activated the classic signs of mitochondrial apoptotic pathway by modulating the recruitment and activation of Bax. ZIKV NS4B represents a novel viral apoptotic protein that can modulate the recruitment and activation of Bax and trigger the apoptotic program. This is a new insight into understanding the interplay between apoptosis and ZIKV infection.