Insights into the seasonal characteristics of single particle aerosols in Chengdu based on SPAMS.

To investigate the seasonal characteristics in air pollution in Chengdu, a single particle aerosol mass spectrometry was used to continuously observe atmospheric fine particulate matter during one-month periods in summer and winter, respectively. The results showed that, apart from O3, the concentrations of other pollutants (CO, NO2, SO2, PM2.5 and PM10) were significantly higher in winter than in summer. All single particle aerosols were divided into seven categories: biomass burning (BB), coal combustion (CC), Dust, vehicle emission (VE), K mixed with nitrate (K-NO3), K mixed with sulfate and nitrate (K-SN), and K mixed with sulfate (K-SO4) particles. The highest contributions in both seasons were VE particles (24%). The higher contributions of K-SO4 (16%) and K-NO3 (10%) particles occurred in summer and winter, respectively, as a result of their different formation mechanisms. S-containing (K-SO4 and K-SN), VE, and BB particles caused the evolution of pollution in both seasons, and they can be considered as targets for future pollution reduction. The mixing of primary sources particles (VE, Dust, CC, and BB) with secondary components was stronger in winter than in summer. In summer, as pollution worsens, the mixing of primary sources particles with 62 [NO3]- weakened, but the mixing with 97 [HSO4]- increased. However, in winter, the mixing state of particles did not exhibit an obvious evolution rules. The potential source areas in summer were mainly distributed in the southern region of Sichuan, while in winter, besides the southern region, the contribution of the western region cannot be ignored.

Identification of whole-genome mutations and structural variations of bile cell-free DNA in cholangiocarcinoma.

Bile cell-free DNA (cfDNA) has been reported as a promising liquid biopsy tool for cholangiocarcinoma (CCA), however, the whole-genome mutation landscape and structural variants (SVs) of bile cfDNA remains unknown. Here we performed whole-genome sequencing on bile cfDNA and analyzed the correlation between mutation characteristics of bile cfDNA and clinical prognosis. TP53 and KRAS were the most frequently mutated genes, and the RTK/RAS, homologous recombination (HR), and HIPPO were top three pathways containing most gene mutations. Ten overlapping putative driver genes were found in bile cfDNA and tumor tissue. SVs such as chromothripsis and kataegis were identified. Moreover, the hazard ratio of HR pathway mutations were 15.77 (95% CI: 1.571-158.4), patients with HR pathway mutations in bile cfDNA exhibited poorer overall survival (P = 0.0049). Our study suggests that bile cfDNA contains genome mutations and SVs, and HR pathway mutations in bile cfDNA can predict poor outcomes of CCA patients.

Adjunctive benefits of low-frequency transcutaneous electrical nerve stimulation for obesity frequent chronic conditions: a systematic review.

Background: Obesity is widely recognized for its role in predisposing individuals to a spectrum of chronic health conditions. Emerging preliminary evidence points to the potential benefits of low-frequency transcutaneous electrical nerve stimulation (Lo-TENS) in enhancing various health outcomes among those with obesity and associated disorders. Objective: This systematic review was designed to assess the effectiveness of Lo-TENS for managing obesity and its related chronic diseases. Methods: For this systematic review, we included randomized controlled trials that evaluated the impact of Lo-TENS on individuals with obesity and its associated chronic diseases. Results: Eight trials encompassing 671 participants and spanning three unique populations: essential hypertension (EH), type 2 diabetes mellitus (T2DM), and obesity were deemed eligible for inclusion in this review. Compared to baseline measurements, Lo-TENS demonstrated a tendency to positively affect blood pressure in individuals with EH and metabolic parameters in those with T2DM. Nonetheless, the efficacy of Lo-TENS in treating obesity is not yet clear when contrasted with a no-intervention control group. When compared with other intervention modalities, three of the trials reported less favorable results. Conclusions: Although Lo-TENS did not consistently surpass other treatments or yield substantial improvements, it generally provided greater benefits than the majority of placebo controls. This suggests that Lo-TENS could potentially serve as a beneficial adjunctive therapy in the management of obesity and its associated conditions. However, given the limited number of trials assessed, the elevated risk of bias within these studies, and the scarce evidence currently available, it is too early to reach definitive conclusions. Caution should be exercised when interpreting the current findings. There is an imperative for further high-quality research to thoroughly investigate and substantiate the efficacy of Lo-TENS in relation to obesity and its related disorders.

Micropeptide MPM regulates cardiomyocyte proliferation and heart growth via the AKT pathway.

The role of micropeptide in cardiomyocyte proliferation remains unknown. We found that MPM (micropeptide in mitochondria) was highly expressed in cardiomyocytes. Compared to MPM+/+ mice, MPM knockout (MPM-/-) mice exhibited reduction in left ventricular (LV) mass, myocardial thickness and LV fractional shortening. RNA-sequencing analysis in H9c2, a rat cardiomyocyte cell line, identified downregulation of cell cycle-promoting genes as the most significant alteration in MPM-silencing cells. Consistently, gain- and loss-of-function analyses in H9c2 cells revealed that cardiomyocyte proliferation was repressed by silencing MPM but was promoted by overexpressing MPM. Moreover, the cardiomyocytes in the hearts of MPM-/- mice displayed reduced proliferation rates. Mechanism investigations disclosed that MPM is crucial for AKT activation in cardiomyocytes. We also identified an interaction between MPM and PTPMT1, and found that silencing PTPMT1 attenuated the effect of MPM in activating the AKT pathway, whereas inhibition of the AKT pathway abrogated the role of MPM in promoting cardiomyocyte proliferation. Collectively, these results indicate that MPM may promote cardiomyocyte proliferation and thus heart growth by interacting with PTPMT1 to activate the AKT pathway. Our findings identify the novel function and regulatory network of MPM and highlight the importance of micropeptides in cardiomyocyte proliferation and heart growth.

Discovery of JAB-3312, a Potent SHP2 Allosteric Inhibitor for Cancer Treatment.

As an oncogenic phosphatase, SHP2 acts as a converging node in the RTK-RAS-MAPK signaling pathway in cancer cells and suppresses antitumor immunity by passing signals downstream of PD-1. Here, we utilized the extra druggable pocket outside the previously identified SHP2 allosteric tunnel site by the (6,5 fused), 6 spirocyclic system. The optimized compound, JAB-3312, exhibited a SHP2 binding Kd of 0.37 nM, SHP2 enzymatic IC50 of 1.9 nM, KYSE-520 antiproliferative IC50 of 7.4 nM and p-ERK inhibitory IC50 of 0.23 nM. For JAB-3312, an oral dose of 1.0 mg/kg QD was sufficient to achieve 95% TGI in KYSE-520 xenograft model of mouse. JAB-3312 was well-tolerated in animal models, and a close correlation was observed between the plasma concentration of JAB-3312 and the p-ERK inhibition in tumors. Currently, JAB-3312 is undergoing clinical trials as a potential anticancer agent.

Post-COVID social engagement and depression among Chinese older adults: exploring rural/urban and gender differences.

PURPOSE: This study investigates the impact of post-COVID social engagement on depression levels among Chinese older adults, with a focus on rural/urban and gender differences. METHODS: Using the year 2018 and year 2020 data from the China Health and Retirement Longitudinal Study (CHARLS), this study analyzed pre- and post-COVID depression levels and social engagement indicators, including going-out, activities and networking among Chinese older adults (N = 8,793). RESULTS: Results showed a significant increase in depression levels across all demographic groups post-COVID, with rural females exhibiting the highest levels of depression. Reduced social engagement was associated with increased depression, particularly among rural males and females. Subgroup analyses highlighted nuanced patterns: rural males suffered from decreased intense activities and online contacts, while urban males experienced heightened depression with reduced visiting and light activities. Rural females reported increased depression with decreased moderate activities and dancing outdoors but decreased levels with reduced online contacts. Conversely, urban females experience decreased depression with reduced social engagements, suggesting areevaluation of priorities amidst pandemic challenges. CONCLUSION: This study has underscored the importance of considering individual, cultural, and contextual factors in understanding mental health outcomes among Chinese older adults. Findings inform targeted interventions aimed at promoting psychological well-being and resilience among Chinese older adults in the post-COVID era, including community-based programs and mental health screenings, to foster social connection and emotional support.

GABA Analogue HSK16149 in Chinese Patients With Diabetic Peripheral Neuropathic Pain: A Phase 3 Randomized Clinical Trial.

Importance: Many patients with diabetic peripheral neuropathic pain (DPNP) experience inadequate relief, despite best available medical treatments. There are no approved and effective therapies for patients with DPNP in China. Objective: To evaluate the efficacy and safety of capsules containing γ-aminobutyric acid (GABA) analogue HSK16149 in the treatment of Chinese patients with DPNP. Design, Setting, and Participants: This phase 2 to 3 adaptive randomized clinical trial was multicenter, double blind, and placebo and pregabalin controlled. The trial started on December 10, 2020, and concluded on July 8, 2022. In stage 1, various doses of HSK16149 were evaluated to determine safety and efficacy for stage 2. The second stage then validated the efficacy and safety of the recommended dose. Intervention: In stage 1, enrolled patients (n = 363) were randomized 1:1:1:1:1:1 to 4 HSK16149 doses (40, 80, 120, or 160 mg/d), pregabalin (300 mg/d), or placebo. In stage 2, patients (n = 362) were randomized 1:1:1 to receive HSK16149, 40 or 80 mg/d, or placebo. The final efficacy and safety analysis pooled data from patients receiving the same treatment. Main Outcomes and Measures: The primary efficacy end point in stage 1 was the change from baseline in average daily pain score (ADPS) at week 5. The primary efficacy end point in stage 2 was the change from baseline in ADPS at week 13. When the final statistical analysis was performed, the P values calculated from the independent data of each phase were combined using the weighted inverse normal method to make statistical inferences. Results: Of 725 randomized patients in the full-analysis set (393 men [54.2%]; mean [SD] age, 58.80 [9.53] years; 700 [96.6%] of Han Chinese ethnicity), 177 received placebo; 178, HSK16149, 40 mg/d; 179, HSK16149, 80 mg/d; 66, HSK16149, 120 mg/d; 63, HSK16149, 160 mg/d; and 62, pregabalin, 300 mg/d. A total of 644 patients (88.8%) completed the study. The 40- and 80-mg/d doses of HSK16149 were recommended in stage 2. At week 13, the ADPS mean (SD) change from baseline was -2.24 (1.55) for the 40-mg/d and -2.16 (1.79) for 80-mg/d groups and -1.23 (1.68) for the placebo group, showing statistical significance for both HSK16149 doses vs placebo (both P < .001). In a safety set (n = 726), 545 patients (75.1%) had adverse events, which were generally mild to moderate, with dizziness and somnolence being the most common. Conclusions and Relevance: Forty- and eighty-mg/d doses of HSK16149 were recommended for treating patients with DPNP in China. The efficacy of HSK16149 capsules was superior to placebo in all groups for relieving DPNP and appeared well tolerated. Trial Registration: ClinicalTrials.gov Identifier: NCT04647773.

ent-Kaurane diterpenoids from Isodon henryi and their anti-inflammatory activities.

Phytochemical investigation of the 70% ethanol extract of Isodon henryi Kudô afforded fifteen ent-kaurane diterpenoids, including nine previously undescribed compounds, named isohenolides C-K (1-9). Compounds 1-6 featured an unusual 6,7;8,15-diseco-7,20-olide ent-kaurane diterpenoid scaffold, in which 1 also possessed an 11,15-lactone ring while 2-6 all contained a free α-methylene-γ-carboxylic acid. Compound 6 was also a rare 6,8-cyclo-7,20-olide ent-kauranoid. Their structures were elucidated primarily by HRESIMS, 1D and 2D NMR spectroscopy, electronic circular dichroism and X-ray diffraction (Cu Kα) methods. Additionally, most compounds were also screened for anti-inflammatory actions against lipopolysaccharide-induced RAW 264.7 cells, and compounds 9 and 13 exhibited stronger nitric oxide inhibition, with IC50 values of 15.99 ± 0.75 and 18.19 ± 0.42 µM, respectively.

Development and validation of a nomogram model for predicting venous thromboembolism risk in lung cancer patients treated with immune checkpoint inhibitors: A cohort study in China.

OBJECTIVE: Venous thromboembolism (VTE) poses a significant threat to lung cancer patients, particularly those receiving treatment with immune checkpoint inhibitors (ICIs). We aimed to develop and validate a nomogram model for predicting the occurrence of VTE in lung cancer patients undergoing ICI therapy. METHODS: The data for this retrospective cohort study was collected from cancer patients admitted to Chongqing University Cancer Hospital for ICI treatment between 2019 and 2022. The research data is divided into training and validation sets using a 7:3 ratio. Univariate and multivariate analyses were employed to identify risk factors for VTE. Based on these analyses, along with clinical expertise, a nomogram model was crafted. The model's predictive accuracy was assessed through receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis, clinical impact curve, and other relevant metrics. RESULTS: The initial univariate analysis pinpointed 13 potential risk factors for VTE. The subsequent stepwise multivariate regression analysis identified age, Karnofsky performance status, chemotherapy, targeted, platelet count, lactate dehydrogenase, monoamine oxidase, D-dimer, fibrinogen, and white blood cell count as significant predictors of VTE. These 10 variables were the foundation for a predictive model, illustrated by a clear and intuitive nomogram. The model's discriminative ability was demonstrated by the ROC curve, which showed an area under the curve of 0.815 (95% CI 0.772-0.858) for the training set, and 0.753 (95% CI 0.672-0.835) for the validation set. The model's accuracy was further supported by Brier scores of 0.068 and 0.080 for the training and validation sets, respectively, indicating a strong correlation with actual outcomes. CONCLUSION: We have successfully established and validated a nomogram model for predicting VTE risk in lung cancer patients treated with ICIs.

Systemic assessment of manual circular stapler versus powered circular stapler for anastomosis in rectal cancer: A large-scale Chinese multicenter prospective cohort study.

Mechanical anastomosis in rectal cancer surgery offers several advantages but is plagued by complications like leaks and strictures. Variations in surgeons' experiences affect outcomes, but powered circular anastomosis has emerged as a promising solution, ensuring uniform staple formation and reducing manual manipulation. This multicenter, randomized, parallel-controlled study in China compared IntoCare™'s powered circular staplers (ICS) with manual circular staplers (MCS) in 382 patients (195 ICS, 187 MCS). Both groups had comparable anastomotic leakage rates. ICS significantly reduced anastomosis time while maintaining similar safety profiles. Postoperative recovery and complication rates were closely matched. The use of ICS in rectal cancer surgeries effectively reduces anastomosis time without compromising safety, offering a promising innovation to enhance the efficacy of rectal cancer surgeries while maintaining patient safety.

Silanol-Stabilized Atomically Dispersed Ptδ+-Ox-Sn Active Sites in Protozeolite for Propane Dehydrogenation.

Crystalline zeolites have been proven to be excellent supports for confining subnanometric metal catalysts to boost the propane dehydrogenation (PDH) reaction. However, the introduced metallic species may suffer from severe sintering and limited stability during the catalytic process, especially when utilizing an industrial impregnation method for metal incorporation. In this study, we developed a new type of support based on amorphous protozeolite (PZ), taking advantage of its adjustable silanol chemistry and zeolitic microporous characteristic for stabilizing atomically dispersed PtSn catalyst via a simple, cost-effective coimpregnation process. The combination of X-ray absorption spectroscopy, X-ray photoelectron spectroscopy, in situ diffuse reflectance infrared Fourier transform spectroscopy under CO atmosphere, and density functional theory calculations confirmed the formation of highly dispersed active Ptδ+-Ox-Sn species in PtSn/PZ. The PtSn/PZ catalyst exhibited a high propane conversion of 45.4% and a high propylene selectivity of 99% (WHSV= 3.6 h-1, 550 °C), with a high apparent rate coefficient of 565 molC3H6·gPt-1·h-1·bar-1 at a high WHSV of 108 h-1, presenting a top-level performance among the state-of-the-art Pt-based catalysts prepared by in situ synthesis and impregnation methods. The silanol density determined the chemical state of PtSn species, showing a change from atomically dispersed Ptδ+-Ox-Sn sites to PtSn alloy with decreasing silanol density of supports. This work provides a general strategy using silanol-rich amorphous protozeolite as support for stabilizing various metal catalysts by the simple impregnation method and also offers an effective way for fine tailoring the chemical state of metallic species via a silanol-engineered approach.

Learning Common Semantics via Optimal Transport for Contrastive Multi-View Clustering.

Multi-view clustering aims to learn discriminative representations from multi-view data. Although existing methods show impressive performance by leveraging contrastive learning to tackle the representation gap between every two views, they share the common limitation of not performing semantic alignment from a global perspective, resulting in the undermining of semantic patterns in multi-view data. This paper presents CSOT, namely Common Semantics via Optimal Transport, to boost contrastive multi-view clustering via semantic learning in a common space that integrates all views. Through optimal transport, the samples in multiple views are mapped to the joint clusters which represent the multi-view semantic patterns in the common space. With the semantic assignment derived from the optimal transport plan, we design a semantic learning module where the soft assignment vector works as a global supervision to enforce the model to learn consistent semantics among all views. Moreover, we propose a semantic-aware re-weighting strategy to treat samples differently according to their semantic significance, which improves the effectiveness of cross-view contrastive representation learning. Extensive experimental results demonstrate that CSOT achieves the state-of-the-art clustering performance.

Analysis of PANoptosis-related ceRNA network reveals lncRNA MIR17HG involved in osteogenic differentiation inhibition impaired by tumor necrosis factor-α.

BACKGROUND: Inflammatory cytokines such as Interleukin 1ß(IL1ß), IL6,Tumor Necrosis Factor-α (TNF-α) can inhibit osteoblast differentiation and induce osteoblast apoptosis. PANoptosis, a newly identified type of programmed cell death (PCD), may be influenced by long noncoding RNA (lncRNAs) which play important roles in regulating inflammation. However, the potential role of lncRNAs in inflammation and PANoptosis during osteogenic differentiation remains unclear. This study aimed to investigate the regulatory functions of lncRNAs in inflammation and apoptosis during osteogenic differentiation. METHODS AND RESULTS: High-throughput sequencing was used to identify differentially expressed genes involved in osteoblast differentiation under inflammatory conditions. Two lncRNAs associated with inflammation and PANoptosis during osteogenic differentiation were identified from sequencing data and Gene Expression Omnibus (GEO) databases. Their functionalities were analyzed using diverse bioinformatics methodologies, resulting in the construction of the lncRNA-miRNA-mRNA network. Among these, lncRNA (MIR17HG) showed a high correlation with PANoptosis. Bibliometric methods were employed to collect literature data on PANoptosis, and its components were inferred. PCR and Western Blotting experiments confirmed that lncRNA MIR17HG is related to PANoptosis in osteoblasts during inflammation. CONCLUSIONS: Our data suggest that TNF-α-induced inhibition of osteogenic differentiation and PANoptosis in MC3T3-E1 osteoblasts is associated with MIR17HG. These findings highlight the critical role of MIR17HG in the interplay between inflammation, PANoptosis, and osteogenic differentiation, suggesting potential therapeutic targets for conditions involving impaired bone formation and inflammatory responses.

Effects of different postharvest drying processes on flavonoid content and enzymatic activity of Styphnolobium japonicum (L.) Schott flowers for industrial and medicinal use.

Traditionally, fresh S. japonicum flowers (SJF) and S. japonicum flowers buds (SJFB) are dried prior to further processing and use. Here, we investigated the ways in which drying techniques, including sun drying (SD), steam drying (STD), microwave drying (MD), hot air drying (HAD, 40 °C, 60 °C, 80 °C, 100 °C), and freeze drying (FD), alter the flavonoid composition of freshly-harvested SJF and SJFB. The flavonoid content of dried samples was determined by Ultra High Performance Liquid Chromatography-Diode Array Detector (UPLC-DAD). Overall, different drying techniques had significantly different effects on the RU content, ranging from 10.63 % (HAD-80 °C) to 34.13 % (HAD-100 °C) in SJF and from 18.91 % (HAD-100 °C) to 29.16 % (HAD-40 °C) and 30.53 % (SD) in SJFB. To clarify the mechanism by which drying affects the RU content of S. japonicum flowers, we studied the activity of a rutin-hydrolyzing enzyme (RHE) isolated from SJF and SJFB using multiple separation and assay methods. According to the Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) results, the apparent molecular weight of the purified RHE was approximately 38 kDa. According to UPLC-DAD, RHE catalyzes the production of quercetin (QU) from rutin (RU), but not from other flavonoid glycosides. Drying fresh SJF and SJFB at low and high temperatures can inhibit RHE activity and prevent RU hydrolysis. Therefore, subjecting freshly-harvest SJF to HAD-100 °C, and freshly-harvest SJFB to SD or HAD-40 °C, can greatly increase the RU content. In particular, HAD is viable for large-scale application due to its simplicity and industrial feasibility.

Numerical simulation of CO2-ECBM for deep coal reservoir with strong stress sensitivity.

CH4 production rate of coalbed methane (CBM) well decreases rapidly during primary recovery in the deeply buried coal seam, resulting in a lot of CH4 residues. CO2 pour into deep coal seam with high stress sensitivity is available for enhancing CH4 recovery by improving permeability for reservoir fracture and displacing CH4 adsorbed in matrix. A coupled adsorp-hydro-thermo-mechanical (AHTM) model for deep methane development is established by considering the coupling relationships of non-isothermal and non-constant pressure competitive adsorption between CO2 and CH4, multi-phase flow, unsteady diffusion, heat transmission and in-situ stress variety. The model is verified by historical production and then used for CO2 enhanced CBM (CO2-ECBM) of deep coal reservoir in a sedimentary basin in Northwest China. The simulation results show that: (1) For primary recovery, permeability in coal reservoir drops rapidly with the development of CBM, which seriously restricts the production of CH4. The permeability of the reservoir decreases from 7.89 × 10-16 m2 to less than 1.50 × 10-16 m2, CH4 production rate in CBM well reduces to below 2000 m3/d, and the average total CH4 content of coal reservoir is reduced by 5.49 m3/t with the decrease of only 1.12 m3/t of average adsorbed CH4 in a production duration of 2000 d (2) With 10 MPa CO2 continuous injection into coal seam after 700d of primary, the permeability for reservoir and CH4 production rate increase while the total CH4 content and adsorption CH4 content in reservoir decrease compared with the primary recovery. (3) CO2 pouring into coal reservoir increases the CH4 production time and rate, which improves CH4 recovery of coal reservoir. And it increases by 23.36 %, 23.07 % and 22.46 % with shut-in thresholds of CH4 production rate of 1000 m3/d, 800 m3/d and 600 m3/d, respectively. The investigation is of great significance for the development of deep coalbed methane.

Single-Cell RNA Sequencing Reveals a Unique Fibroblastic Subset and Immune Disorder in Lichen Sclerosus Urethral Stricture.

Purpose: Lichen sclerosus urethral stricture disease (LS USD) is a refractory and progressive disease primarily affecting the anterior urethra in males. Various potential etiological factors, such as genetics, autoimmunity, infection, and exposure to infectious urine, have been suggested. However, the accurate etiology of LS in the male urethra remains unclear. Patients and Methods: In this study, we conducted single-cell RNA sequencing to identify the transcriptional profiles of three patients with LS USD and three patients with non-LS USD. Immunofluorescence was used to confirm the single-cell sequence results. Results: Our study revealed distinct subsets of vein endothelial cells (ECs), smooth muscle cells (SMCs), and fibroblasts (FBs) with high proportions in LS USD, contributing to the tissue microenvironment primarily involved in proinflammatory and immune responses. In particular, FBs displayed a unique subset, Fib7, which is exclusively present in LS USD, and exhibited high expression levels of SAA1 and SAA2. The accumulation of macrophages, along with the dysregulated ratios of M1/M2-like phenotype macrophages, may be engaged in the pathogenesis of LS USD. Through cell-cell communication analysis, we identified significant interactions involving CXCL8/ACKR1 and CCR7/CCL19 in LS USD. Remarkably, Fib7 exhibited exclusive communication with IL-1B macrophages through the SAA1/FPR2 receptor-ligand pair. Conclusion: Our study provides a profound understanding of the tissue microenvironment in LS USD, which may be valuable for understanding the pathogenesis of LS USD.

Ionic Covalent Organic Framework Solid-State Electrolytes.

Rechargeable secondary batteries, widely used in modern technology, are essential for mobile and consumer electronic devices and energy storage applications. Lithium (Li)-ion batteries are currently the most popular choice due to their decent energy density. However, the increasing demand for higher energy density has led to the development of Li metal batteries (LMBs). Despite their potential, the commonly used liquid electrolyte-based LMBs present serious safety concerns, such as dendrite growth and the risk of fire and explosion. To address these issues, using solid-state electrolytes in batteries has emerged as a promising solution. In this Perspective, recent advancements are discussed in ionic covalent organic framework (ICOFs)-based solid-state electrolytes, identify current challenges in the field, and propose future research directions. Highly crystalline ion conductors with polymeric versatility show promise as the next-generation solid-state electrolytes. Specifically, the use of anionic or cationic COFs is examined for Li-based batteries, highlight the high interfacial resistance caused by the intrinsic brittleness of crystalline ICOFs as the main limitation, and presents innovative ideas for developing all- and quasi-solid-state batteries using ICOF-based solid-state electrolytes. With these considerations and further developments, the potential for ICOFs is optimistic about enabling the realization of high-energy-density all-solid-state LMBs.

Racial and Ethnic Disparities in Primary Total Knee Arthroplasty Outcomes: A Systematic Review and Meta-Analysis of Two Decades of Research.

Racial disparities in outcomes following total knee arthroplasty (TKA) remain persistent. This systematic review and meta-analysis aims to comprehensively synthesize data between 2000-2020. An electronic search of studies was performed on PubMed, SCOPUS, and the Cochrane Library databases from January 1, 2000, and December 31, 2020. Random effects models were used to report unadjusted and adjusted estimates for a comprehensive list of care outcomes in TKA. 63 studies met PRISMA criteria. Black patients report greater odds of in-hospital mortality (odds ratio [OR]: 1.37, 95% CI: 1.00-1.59 (p = 0.049); adjusted OR [aOR]: 1.34, 95% CI: 1.09-1.64), in-hospital complications (OR: 1.31, 95% CI: 1.27-1.35), 30-day complications (aOR: 1.19, 95% CI: 1.07-1.33), infection (OR: 1.11, 95% CI: 1.07-1.16; aOR: 1.30, 95% CI: 1.16-1.46), bleeding (OR: 1.33, 95% CI: 1.03-1.71; aOR: 1.47, 95% CI: 1.23-1.75), peripheral vascular events (PVE) (aOR: 1.46, 95% CI: 1.11-1.92), length of stay (LOS) (OR: 1.20, 95% CI: 1.08-1.34), extended-LOS (aOR: 1.89, 95% CI: 1.53-2.33), discharge disposition (OR: 1.59, 95% CI: 1.29-1.96; aOR: 1.96, 95% CI: 1.70-2.25), 30-day (OR: 1.20, 95% CI: 1.13-1.27; aOR: 1.17 95% CI: 1.09-1.26) and 90-day (OR: 1.46, 95% CI: 1.17-1.82) readmission compared to White patients. Disparities in bleeding, extended-LOS, discharge disposition, PVE, and 30-day readmission were observed in Asian patients. Hispanic patients experienced disparities in extended LOS and discharge disposition, while Native-American patients had disparities in bleeding outcomes. Persistent racial disparities in TKA outcomes highlight a need for standardized outcome measures and comprehensive data collection across multiple racial groups to ensure greater healthy equity.

Smoking, Alcohol Consumption, and Risk of Arterial Stiffness: A Two-Sample Mendelian Randomization Study.

Background: While observational studies have demonstrated connections between cigarette smoking, alcohol consumption, and arterial stiffness, establishing a causal relationship has proven challenging because of potential confounding factors. To address this problem, we employed a two-sample Mendelian randomization approach. Methods: We selected genetic instruments for these risk factors from genome-wide association studies encompassing 3,383,199 individuals at the genome-wide significance level (p < 5 × 10 - 9 ). Arterial stiffness data were acquired from the UK Biobank, which included 127,121 participants. Our primary analysis utilized the inverse variance-weighted method to explore causality. To confirm our results' robustness, we conducted sensitivity analyses using Egger regression, the weighted median method, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO). Results: Our analysis revealed a significant association between genetic inclination to smoking initiation and an increase in the arterial stiffness index ( ß = 0.11; 95% confidence interval [CI], 0.06 to 0.16; p = 1.95 × 10 - 5 ). Additionally, there was a suggestive connection between genetically predicted number of cigarettes per day and the arterial stiffness index ( ß = 0.05; 95% CI, 5.25 × 10 - 4 to 0.10; p = 4.75 × 10 - 2 ). No causal relationships were observed between the genetically predicted age of smoking initiation, smoking cessation, or alcohol consumption and the risk of arterial stiffness index. Conclusions: This Mendelian randomization study indicates that smoking initiation is likely a causative risk factor for arterial stiffness. However, further research is needed to determine if the quantity of daily cigarettes directly contributes to arterial stiffness development. Regarding alcohol consumption, age of smoking initiation, and smoking cessation, there was insufficient evidence to establish causality.