Solvent-Free Synthesis Enables Encapsulation of Subnanometric FeOx Clusters in Pure Siliceous Zeolites for Efficient Catalytic Oxidation Reactions.

Metal/metal oxide clusters possess a higher count of unsaturated coordination sites than nanoparticles, providing multiatomic sites that single atoms do not. Encapsulating metal/metal oxide clusters within zeolites is a promising approach for synthesizing and stabilizing these clusters. The unique feature endows the metal clusters with an exceptional catalytic performance in a broad range of catalytic reactions. However, the encapsulation of stable FeOx clusters in zeolite is still challenging, which limits the application of zeolite-encapsulated FeOx clusters in catalysis. Herein, we design a modified solvent-free method to encapsulate FeOx clusters in pure siliceous MFI zeolites (Fe@MFI). It is revealed that the 0.3-0.4 nm subnanometric FeOx clusters are stably encapsulated in the 5/6-membered rings intersectional voids of the pure siliceous MFI zeolites. The encapsulated Fe@MFI catalyst with a Fe loading of 1.4 wt % demonstrates remarkable catalytic activity and recycle stability in the direct oxidation of methane, while also promoting the direct oxidation of cyclohexane, surpassing the performance of conventional zeolite-supported Fe catalysts.

The epidemiology and clinical features of post-exposure prophylaxis for rabies: A retrospective study of 9772 cases.

Background: In December 2015, the World Health Organization, the World Animal Health Organization, and the Food and Agriculture Organization of the United Nations convened the International Congress on the elimination of rabies in Geneva. How to use epidemiological factors of post-exposure prophylaxis to prevent rabies has become the focus of attention. Objective: To analyze the epidemiological characteristics of 9772 patients with rabies in a four-year period in one hospital, to clarify the outbreak law of rabies and to explore the corresponding prevention and control strategies. Methods: The epidemiological data of rabies patients were collected from the infectious disease reporting information management system of the hospital from July 2018 to June 2022. The distributional characteristics of 13 influencing factors were analyzed using the chi-square test and linear regression. Results: There was a significant correlation between the number of wounds and age, and the numbers of female and male patients were close. People over the age of 44 were more likely to get bites or scratches on their lower extremity (P<0.0001). There was a greater possibility for elderly people to be bitten by dogs (P<0.0001). Dogs preferred to bite or scratch lower limbs (P<0.0001), while cats upper limbs (P<0.0001). Upper limbs were more possibly attacked by animals at home (P<0.0001). There were significant correlations among exposure grade, wound treatment and number of wounds. Conclusions: Lower extremity protection is needed for the elderly and when encountering dogs, and more attention needs to be paid to the upper extremities when encountering cats and household pets, as well as pets that are cute but need to be protected from bites or scratches.

Targeted screening of multiple anti-inflammatory components from Chrysanthemi indici Flos by ligand fishing with affinity UF-LC/MS.

Chrysanthemi indic Flos (CIF) has been commonly consumed for the treatment of inflammation and related skin diseases. However, the potential bioactive components responsible for its anti-inflammatory and sensitive skin (SS) improvement activities, and the correlated mechanisms of action still remain unknown. In this work, it was firstly found that the CIF extract (CIFE) displayed arrestive free radical scavenging activity on DPPH and ABTS radicals, with no significant difference with positive control Trolox (p > 0.05). Then, compared to the negative group, CIFE markedly decreased the productions of the pro-inflammatory cytokines (IL-1ß, IL-6, PEG2, TNF-α, IFN-γ, NO) in LPS induced RAW264.7 cells in a dose-dependent manner (p < 0.01). Besides, CIFE strongly inhibited the COX-2 and hyaluronidase (HAase) with the IC50 values of 1.06 ± 0.01 µg/mL and 12.22 ± 0.39 µg/mL, indicating higher inhibitory effect than positive control of aspirin of 6.33 ± 0.05 µg/mL (p < 0.01), and comparable inhibitory effect with indometacin of 0.60 ± 0.03 µg/mL, and ascorbic acid of 11.03 ± 0.41 µg/mL (p > 0.05), respectively. Furthermore, kinetic assays with Lineweaver-Burk plot (Michaelis Menten equation) suggested that CIFE reversibly inhibited the COX-2 and HAase, with a mixed characteristics of competitive and non-competitive inhibition. Thereafter, multi-target affinity ultrafiltration liquid chromatography-mass spectrometry (UF-LC/MS) method was employed to fast fish out the potential COX-2 and HAase in CIFE. Herein, 13 components showed various affinity binding degrees to the COX-2 and HAase, while those components with relative binding affinity (RBA) value higher than 3.0, such as linarin and chlorogenic acid isomers, were deemed to be the most bioactive components for the anti-inflammatory and SS improvement activities of CIFE. Finally, the interaction mechanism, including binding energy, inhibition constant, docking sites, and the key amino acids involved in hydrogen bonds between the potential ligands and COX-2/HAase were simulated and confirmed with the molecule docking analysis. In summary, this study showcased the prominent anti-inflammatory and SS improvement activities of CIF, which would provide further insights on this functional medicinal plant to be a natural anti-SS remedy.

Phthalate exposure and subfecundity in preconception couples: A nested case-control study.

BACKGROUND: Phthalates (PAEs) are endocrine-disrupting chemicals ubiquitously found in the environment. This study aimed to examine the association between exposure of PAEs and subfecundity in preconception couples. METHODS: This is a nested case-control study based on preconception cohort. Preconception couples with intention to conceive were enrolled and followed up until a clinically confirmed pregnancy or 12 menstrual cycles of preparation for conception. A total of 107 couples with subfecundity- time to pregnancy (TTP) more than 12 menstrual cycles, and 144 couples ≤12 cycles were included in the analysis. The levels of PAE metabolites in one spot urine samples were detected and compared between the groups. The weighted quantile sum (WQS) regression model and Bayesian kernel machine regression (BKMR) model were used to examine the joint effects of couples' exposure to PAEs on subfecundity. RESULTS: Using the multivariate binary logistic regression model, compared to the lowest quartile of urinary ∑PAEs concentration group, both preconception females (aOR=2.42, 95% CI: 1.10-5.30, p=0.027) and males (aOR=2.99, 95% CI: 1.36-6.58, p=0.006) in the highest quartile group had an increased risk of subfecundity, and a dose-response relationship was observed between PAEs and the risk of subfecundity. The WQS analyses found that co-exposure to PAE mixture was a risk factor for subfecundity in preconception female (aOR=1.76, 95% CI: 1.38-2.26, p<0.001), male (aOR=1.58, 95% CI: 1.20-2.08, p=0.001), and couple (aOR=2.39, 95% CI: 1.61-3.52, p<0.001). The BKMR model found a positive combined effect of mixed exposure to PAEs on the risk of subfecundity. CONCLUSIONS: PAEs increase the risk of subfecundity in preconception couples. Our research reinforced the need of monitoring PAE exposure for the purpose of improving human reproductive health.

The calculated electronic and optical properties of ß-Ga2O3 based on the first principles.

INTRODUCTION: The electronic and optical properties of ß-Ga2O3 have been investigated by CASTEP using first principles. It is found that ß-Ga2O3 has an indirect band gap and the conduction band base is located at the Γ point. The stability of ß-Ga2O3 is demonstrated by the calculation of elastic constants, and the ductility of ß-Ga2O3 is demonstrated by the ratio of Poisson's ratio to shear modulus. The optical property analysis shows that ß-Ga2O3 has a high absorption capacity in the ultraviolet region, but a low absorption capacity in visible and infrared light. CONTEXT: The structure, optical, and electronic properties of ß-Ga2O3 are calculated and analyzed based on first-principles calculation. The optimized structures of ß-Ga2O3 are in good agreement with previously studied. In this paper, the elastic, electronic, and optical properties of ß-Ga2O3 are calculated. METHODS: The CASTEP code was employed to execute these calculations in the present work, where the exchange-correlation interactions were treated in the generalized gradient approximation (GGA) using the Perdew-Burke-Ernzerhof (PBE) functional in the geometry optimizations and electronic and elastic properties.

Novel Peptide DR3penA as a Low-Toxicity Antirenal Fibrosis Agent by Suppressing the TGF-ß1/miR-212-5p/Low-Density Lipoprotein Receptor Class a Domain Containing 4/Smad Axis.

Renal fibrosis is a complex pathological process that contributes to the development of chronic kidney disease due to various risk factors. Conservative treatment to curb progression without dialysis or renal transplantation is widely applicable, but its effectiveness is limited. Here, the inhibitory effect of the novel peptide DR3penA (DHα-(4-pentenyl)-AlaNPQIR-NH2), which was developed by our group, on renal fibrosis was assessed in cells and mice with established fibrosis and fibrosis triggered by transforming growth factor-ß1 (TGF-ß1), unilateral ureteral obstruction, and repeated low-dose cisplatin. DR3penA preserved renal function and ameliorated renal fibrosis at a dose approximately 100 times lower than that of captopril, which is currently used in the clinic. DR3penA also significantly reduced existing fibrosis and showed similar efficacy after subcutaneous or intraperitoneal injection. Mechanistically, DR3penA repressed TGF-ß1 signaling via miR-212-5p targeting of low-density lipoprotein receptor class a domain containing 4, which interacts with Smad2/3. In addition to having good pharmacological effects, DR3penA could preferentially target injured kidneys and exhibited low toxicity in acute and chronic toxicity experiments. These results unveil the advantages of DR3penA regarding efficacy and toxicity, making it a potential candidate compound for renal fibrosis therapy.

A Soy Protein-Based Film Based on Chemical Treatment and Microcrystalline Cellulose Reinforcement Obtained from Corn Husk Byproducts.

Developing an environmentally friendly soy protein-based film that offers excellent performance has garnered considerable interest while also posing a significant challenge. Herein, we propose the strategy of covalent and noncovalent cross-linking to improve the mechanical properties of the films. First, chemical denaturation was carried out under the combined action of sodium sulfite, sodium dodecyl sulfate, sodium hydroxide, and urea to reshape the structure of the protein to improve the solubility of protein and release active groups. Then, microcrystalline cellulose (MCC) derived from low-cost agro-industrial byproducts (corn husk) was employed to balance the covalent cross-linking reaction between proteins and the noncovalent reaction between MCC and protein. The results indicate that the structure and properties of the soy protein-based films were modified and improved through chemical treatment in conjunction with biomass enhancement. It is concluded that the addition of 1% MCC improves the tensile strength, elastic modulus, water solubility, and water vapor permeability of "MCC-1%" by 64.7, 75.9, 22.7, and 12.9%, respectively. Additionally, the resulting film of "MCC-1%" exhibits better resistance to thermal degradation and improved thermo-stability. However, the elongation at break decreased by increasing the addition of MCC. Thus, this work may provide a simple and affordable approach to preparing a high-performing soy protein-based film.

The influence of pontic distribution on the marginal and internal gaps of CAD/CAM five-unit anterior zirconia framework.

Background/purpose: Nowadays, zirconia-based framework has been used for longspan or full-arch fixed dental prostheses (FDPs). This study aimed to evaluate the effect of pontic distribution on marginal and internal gaps of five-unit anterior zirconiabased DPs. Materials and methods: Right maxillary central incisor and second premolar were selected as terminal abutments and three different edentulous conditions with one nonterminal abutment were simulated. Marginal and internal gaps in each zirconia-based samples(n = 10) were examined by computer-aided replica technique. Five regions, including marginal gaps at mesial or distal finishing line, internal gaps at the mesial or distal axial wall, and occlusal surface, were statistically analyzed (α = .05). Results: Most of marginal gaps and internal gaps at axial wall were clinically acceptable, but larger at occlusal surface. For the three experimental groups, clinically accepted percentage with qualified gaps were less than 30%.There were statistical differences at axial wall over pontic side and marginal gaps over non-pontic side between groups (P<0.05). For sum of gaps of all abutments in each group, statistical differences were found at marginal and axial wall (P < 0.05). As for those on terminal and non-terminal abutments, statistical differences were found on second premolar (P < 0.05). Conclusion: Except for occlusal surface, the overall marginal gaps and internal gaps at axial wall of five-unit anterior zirconia-based FDPs with different pontic distribution were clinically acceptable. However, the percentage with qualified gaps were low (<30%). Greater gaps were noted when adjacent pontic existed. Different pontic size and distribution with curvature had an influence on the gaps.

The Association between Vitamin D Deficiency and the Risk of Mortality after Hip Fractures: A Systematic Review and Meta-Analysis.

Prevalence of hip fractures is on the rise and is associated with high mortality, especially in aging patients. Vitamin D is routinely recommended for bone health in general population. Our study explores the potential association between low levels (≤20 ng/mL) of vitamin D and mortality in hip fracture patients. Systematic search was done for studies that were published from inception until May 10, 2023, and that report a possible correlation between low vitamin D levels and mortality in patients with hip fractures. A random-effects model was used to assess the effects of normal vitamin D levels on mortality, subgroup analyses were conducted to assess the link between low levels of vitamin D and geographic location of the study and its impact on the recovery process. In 575 identified studies, 18 met the inclusion criteria. A strong connection between low serum levels of vitamin D (<20 ng/mL) and mortality (hazard ratio (HR): 2.29, p<0.001). Further analysis indicated that insufficient (20 to 30 ng/mL) and sufficient (>30 ng/mL) levels of vitamin D levels did not have a significant association with the mortality (HR: 1.10, p=0.12), and (HR: 1.04, p=0.50). As shown by subgroup analysis vitamin D deficiency significantly correlated with mortality in studies conducted in Europe (HR: 2.4). Our results clearly demonstrate that vitamin D deficiency is associated with higher risk of mortality in hip fracture patients. Additional analyses demonstrate that insufficient and sufficient levels of vitamin D were not significantly associated with mortality outcomes in hip fracture patients.

Comparatively analysing the postoperative optical performance of different intraocular lenses: a prospective observational study.

BACKGROUND: Postoperative performance, including best corrected distance visual acuity (BCDVA) and optical metrics (from the OQAS and iTrace devices), was compared among 4 different intraocular lenses (IOLs). METHODS: This prospective observational study included 104 eyes from 104 subjects who underwent cataract surgery combined with implantation of 4 different IOLs: monofocal (Mon) IOLs, segmental refractive (SegRef) IOLs, diffractive (Dif) IOLs and extended depth of focus (EDoF) IOLs. Postoperative BCDVA and optical metrics were collected at the 6th month. The OQAS optical metrics included the objective scattering index (OSI), Strehl ratio (SR), modulation transfer function (MTF) cut-off frequency, and predicted visual acuity (PVA); the iTrace optical metrics included blur/double vision, glare/halo, starburst, mixed focus, night myopia, and night hyperopia. RESULTS: There was no significant difference in BCDVA among the 4 groups (P = 0.059; power = 70.3%). Differences were observed in all OQAS optical metrics among the groups (all P < 0.001). Overall, Mon IOLs and EDoF IOLs exhibited better performance than Dif IOLs and SegRef IOLs. Starburst was the only iTrace optical metric that differed among the groups (P < 0.001): SegRef IOLs caused more starbursts than Mon IOLs (P = 0.001), Dif IOLs (P = 0.006) and EDoF IOLs (P < 0.001). Spearman rank correlation analysis was used to determine the relationships among the iTrace optical metrics, OQAS optical metrics and BCDVA: starburst was negatively correlated with BCDVA, PVA at contrasts of 100% and 20%, OSI, and MTF cut-off frequency (all P ≤ 0.001); mixed focus was positively correlated with BCDVA, PVA at contrasts of 100% and 20%, OSI, and MTF cut-off frequency (all P ≤ 0.001). CONCLUSIONS: Postoperative BCDVA and optical metrics varied among the different IOLs, which should be taken into account in the selection and management of IOLs for cataract patients. TRIAL REGISTRATION: This study was approved by the First Affiliated Hospital of Guangzhou Medical University Ethical Review Board (No. 50 2022).

Safety, tolerability, and pharmacokinetics of aildenafil citrate tablets, a novel oral PDE5 inhibitor, in healthy Chinese volunteers after multiple-dose administration.

Background: Aildenafil citrate is a potent and selective inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase type 5, developed for the treatment of erectile dysfunction (ED). Aim: This study aimed to assess the pharmacokinetics, safety, and tolerability of aildenafil citrate tablets after multiple doses in healthy Chinese males. Methods: Twenty participants were divided into 2 groups, 10 participants each. Participants were administered multiple doses of aildenafil citrate tablets at 30 and 60 mg. Outcomes: The safety evaluation was based on clinical symptoms and adverse events. Concentrations of aildenafil and its key metabolites (M1, M5, and M12) in human serum were measured by liquid chromatography-tandem mass spectrometry. Results: Pharmacokinetic analysis showed rapid absorption and elimination of aildenafil, with a median time to maximum serum concentration of 1 hour and mean terminal half-lives of 2.75 and 3.26 hours in the respective dose groups. The mean maximum concentration was proportional to the aildenafil dose in the range of 30 to 60 mg, although the area under the curve was not proportional for serum concentration vs time 0 to the last measurable time point (24 hours). Multiple doses of aildenafil were well tolerated, with 60.0% of men experiencing treatment-emergent adverse events, notably myalgia and fatigue, particularly in the 60-mg group. Clinical Implications: Aildenafil citrate tablets demonstrated favorable tolerability with once-daily administration over the clinical dose range. The occurrence of myalgia and fatigue was more prevalent in the 60-mg group. From a pharmacokinetic perspective, optimal administration of aildenafil citrate tablets appears to be 1 hour before sexual intercourse in men with ED. Strengths and Limitations: This study presents robust safety and pharmacokinetic data at expected therapeutic doses, unaffected by clinical factors. The efficacy of aildenafil citrate tablets warrants further validation in individuals with ED. Conclusion: Aildenafil citrate tablets exhibited good tolerability in healthy Chinese males following multiple doses at 30 and 60 mg. The 60-mg group showed an increased incidence of myalgia and fatigue, suggesting the need for heightened clinical vigilance. The mean maximum concentration, but not the area under the curve, displayed dose proportionality within the 30- to 60-mg dose range, and no significant drug accumulation was observed with repeated daily administration. Clinical Trial Registration: CTR20192473 (http://www.chinadrugtrials.org.cn).

Intravenous immunoglobulin protects the integrity of the intestinal epithelial barrier and inhibits ferroptosis induced by radiation exposure by activating the mTOR pathway.

Radiation exposure often leads to serious health problems in humans. The intestinal epithelium is sensitive to radiation damage, and radiation causes destruction of the intestinal epithelial barrier, which leads to radiation enteritis (RE), the loss of fluids, and the translocation of intestinal bacteria and toxins; radiation can even threaten survival. In this study, we aimed to explore the influence of IVIg on the integrity of the intestinal epithelial barrier after RE. Using a RE mouse model, we investigated the protective effects of intravenous immunoglobulin (IVIg) on the epithelial junctions of RE mice and validated these findings with intestinal organoids cultured in vitro. In addition, transmission electron microscopy (TEM), western blotting (WB) and immunostaining were used to further investigate changes in intestinal epithelial ferroptosis and related signaling pathways. When RE occurs, the intestinal epithelial barrier is severely damaged. IVIg treatment significantly ameliorated this damage to epithelial tight junctions both in vivo and in vitro. Notably, IVIg alleviated RE by inhibiting intestinal epithelial ferroptosis in RE mice. Mechanistically, IVIg promoted activation of the mTOR pathway and inhibited ferroptosis in the intestinal epithelium of mice. Rapamycin, which is a potent inhibitor of the mTOR protein, significantly abolished the protective effect of IVIg against radiation-induced damage to intestinal epithelial tight junctions. Overall, IVIg can prevent RE-induced damage to the intestinal epithelial barrier and inhibit ferroptosis by activating the mTOR pathway; this study provides a new treatment strategy for patients with RE caused by radiotherapy or accidental nuclear exposure.

Identification of Coding Variants in 10q22.1 Associated with Vitiligo in the Chinese Han Population.

Objective: This study aims to identify causal variants associated with vitiligo in an expanded region of 10q22.1. Materials and Methods: We conducted a fine-scale deep analysis of the expanded 10q22.1 region using in a large genome-wide association studies dataset consisting of 1117 cases and 1701 controls through imputation. We selected five nominal coding single nucleotide polymorphisms (SNPs) located in SLC29A3 and CDH23 and genotyped them in an independent cohort of 2479 cases and 2451 controls in a Chinese Han population cohort using the Sequenom MassArray iPLEX1 system. Results: A missense SNP in SLC29A3, rs2252996, showed strong evidence of association with vitiligo (p = 1.34 × 10-8, odds ratio [OR] = 0.82). Three synonymous SNPs (rs1084004 in SLC29A3; rs12218559 and rs10999978 in CDH23) provided suggestive evidence of association for vitiligo (p = 1.69 × 10-6, OR = 0.84; p = 9.47 × 10-5, OR = 1.18; p = 6.90 × 10-4, OR = 1.16, respectively). Stepwise conditional analyses identified two significant independent disease-associated signals from the four SNPs (both p < 0.05; both D' = 0.03; and r2 = 0.00). Conclusion: The study identifies four genetic coding variants in SLC29A3 and CDH23 on 10q22.1 that may contribute to vitiligo susceptibility with one missense variant affecting disease subphenotypes. The presence of multiple genetic variants underscores their significant role in the genetic pathogenesis of the disease.

Chinese parents' intention to vaccinate their 0-5-year-old children with the EV-71 vaccine against hand, foot, and mouth disease and willingness-to-pay.

Background: This study aimed to determine the intention and willingness-to-pay (WTP) of Chinese parents/guardians to vaccinate their children with the EV-71 vaccine. Knowledge levels about hand, foot, and mouth disease (HFMD) and the EV-71 vaccine were also investigated. Methods: A cross-sectional, self-administered online survey was conducted between November 2022 and March 2023. A stratified multi-stage random sampling method was used to recruit parents/guardians of children aged 0-5 years in southeastern China. Results: A total of 3,626 complete responses were received. The mean knowledge score of HFMD was 9.99 (±4.23) out of a total of 14 points. The majority of the participants reported a somewhat willing intent (58.8%), followed by an extremely willing intent (28.9%). Participants who did not consider the EV-71 vaccine expensive (OR = 2.94, 95%CI 2.45-3.53) perceived that the EV-71 vaccine is effective (OR = 2.73, 95%CI 1.52-4.90), and a high knowledge level of HFMD (OR = 1.90, 95%CI 1.57-2.29) had the highest significant odds of having an extremely willing intent to vaccinate their children with the EV-71 vaccine. The median (interquartile range [IQR]) of WTP for the EV-71 vaccine was CNY¥200/USD$28 (IQR CNY¥100-400/USD$14-56). The highest marginal WTP for the vaccine was mainly influenced by the perceived high cost of the vaccine. Those participants who did not consider the EV-71 vaccine expensive had more than 10 times higher odds of vaccinating their children (OR = 10.86, 95%CI 8.49-13.88). Perceived susceptibility, perceived benefits, and perceived barriers were also significant influencing factors in the highest marginal WTP. Conclusion: The findings demonstrate the importance of improving health promotion and reducing the barriers to EV-71 vaccination. Therefore, it is important to improve health promotion and reduce the barriers to EV-71 vaccination.

[Mechanism of acteoside in prevention and treatment of gouty arthritis based on liver metabolomics].

This study aims to reveal the effect of acteoside on gouty arthritis(GA) in rats based on liver metabolomics. The ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to search for the potential biomarkers and metabolic pathways. SD rats were randomly assigned into blank, model, colchicine(0.3 mg·kg~(-1)), and high-, medium-, low-dose(200, 100, and 50 mg·kg~(-1), respectively) acteoside groups(n=7). The rats were administrated once a day for 7 continuous days. Monosodium urate(MSU) was used to induce GA model in rats during administration. The degree of joint swelling and pathological changes of synovial tissue in rats were observed, and the levels of interleukin(IL)-1ß, IL-18 and tumor necrosis factor(TNF)-α in the synovial tissue of rats were measured. UPLC-Q-TOF-MS was employed to collect rat liver data, and Progenesis QI and EZ info were used for data analysis. Human Metabolomics Database(HMDB) and Kyoto Encyclopedia of Genes and Genomes(KEGG) were employed to predict the potential biomarkers and metabolic pathways. The results showed that acteoside alleviated joint swelling, reduced synovial tissue damage, and lowered the levels of inflammatory cytokines in GA rats. A total of 19 common biomarkers were identified, 17 of which can be regulated by acteoside. Seven metabolic pathways were enriched, such as glycerophospholipid metabolism, linoleic acid metabolism, and taurine and hypotaurine metabolism, among which glycerophospholipid metabolism was strongly disturbed. The metabolomics analysis suggested that acteoside may down-regulate the expression of inflammatory cytokines and alleviate the symptoms of GA rats by regulating glycerophospholipid metabolism, linoleic acid metabolism, and taurine and hypotaurine metabolism. The findings provide a reference for future research and development of acteoside.

Adalimumab exhibits superiority over etanercept in terms of a numerically higher response rate and equivalent adverse events: A real-world finding.

INTRODUCTION: Adalimumab (ADA) and etanercept (ETN) are the most commonly applied biologics for rheumatoid arthritis (RA) management in China; however, the evidence regarding their superiority is controversial. In addition, in real-world clinical settings, many factors may affect the application of these agents, such as dosage and administration period. Therefore, the present real-world study aimed to compare the efficacy and safety of ADA and ETN treatment in RA patients via the propensity score matching method. METHODS: In total, 105 RA patients receiving ADA (n = 66) or ETN (n = 39) were reviewed in this retrospective study. The propensity score matching method was used to eliminate discrepancies in baseline features. Clinical response, low disease activity (LDA), and remission were evaluated based on the DAS28. RESULTS: Before propensity score matching, compared with ETN, ADA yielded higher rates of clinical response at W24 (97.0% vs. 84.6%, p = .021), LDA at W12 (78.8% vs. 51.3%, p = .003), and remission at W24 (75.8% vs. 46.2%, p = .002). After propensity score matching, compared with ETN, ADA only achieved a higher rate of clinical response at W24 (96.3% vs. 77.8%, p = .043), whereas the rates of LDA and remission were not different between ADA and ETN treatments at any time point (all p > .05). In addition, the incidence of adverse events was not significantly different between the ADA and ETN treatments (all p > .05). CONCLUSION: ADA shows superiority over ETN in terms of a numerically greater response rate and equivalent adverse events.

Application of improved GalNAc conjugation in development of cost-effective siRNA therapies targeting cardiovascular diseases.

N-Acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA) therapies have received approval for treating both orphan and prevalent diseases. To improve in vivo efficacy and streamline the chemical synthesis process for efficient and cost-effective manufacturing, we conducted this study to identify better designs of GalNAc-siRNA conjugates for therapeutic development. Here, we present data on redesigned GalNAc-based ligands conjugated with siRNAs against angiopoietin-like 3 (ANGPTL3) and lipoprotein (a) (Lp(a)), two target molecules with the potential to address large unmet medical needs in atherosclerotic cardiovascular diseases. By attaching a novel pyran-derived scaffold to serial monovalent GalNAc units before solid-phase oligonucleotide synthesis, we achieved increased GalNAc-siRNA production efficiency with fewer synthesis steps compared to the standard triantennary GalNAc construct L96. The improved GalNAc-siRNA conjugates demonstrated equivalent or superior in vivo efficacy compared to triantennary GalNAc-conjugated siRNAs.