Association between sarcopenia and sleep disorders: a cross-sectional population based study.

Objective: Sleep disorders is a worldwide public health problem. We sought to examine the association between sarcopenia, a decline in skeletal muscle mass and function, and sleep disorders within the adult demographic of the United States during the period spanning 2011 to 2018. Methods: Diagnosis of sarcopenia and sleep disorders was ascertained through appropriate calculations and a structured questionnaire. The primary correlation analysis was conducted using a weighted multivariate logistic regression model. Furthermore, to confirm the presence of a potential non-linear association between sarcopenia and sleep disorders, additional analyses were performed using multivariate logistic regression and restricted cubic spline (RCS) regression with dose-response curve analysis. Subgroup analyses were also conducted to explore the influence of relevant socio-demographic factors and other covariates. Results: The final analysis encompassed 5,616 participants. Model 4, inclusive of all pertinent covariates, revealed a positive correlation between sarcopenia and sleep disorders, yielding an odds ratio (OR) of 1.732 (95% CI: 1.182-2.547; P = 0.002). Further analysis, utilizing the restricted cubic spline model, indicated a decreasing trend in sleep disorders as sarcopenia indices rose. Stratified analyses across diverse variables underscored the significant impact of sarcopenia on sleep disorders prevalence in several subgroups. Specifically, males, individuals aged 40 and above, non-Hispanic whites, those with high school education or equivalent, unmarried individuals, obese individuals (BMI ≥ 30), alcohol drinkers, former smokers, diabetics, and those engaging in less rigorous recreational activities exhibited a more pronounced association between sarcopenia and sleep disorders. The incidence of sleep disorders exhibited an upward trend as the incidence of sarcopenia declined among study participants. Conclusions: In summary, our study provides evidence of an association between sarcopenia and the prevalence of sleep disorders, with a negative correlation observed between the sarcopenia index and the odds ratio of sleep disorders. These findings suggest that maintaining optimal muscle mass may have a beneficial impact on sleep-related issues. In terms of exploring the mechanisms underlying the relationship between sarcopenia and sleep disorders, more in-depth research is warranted to ascertain the definitive causal relationship.

Clinical-imaging metrics for the diagnosis of prostate cancer in PI-RADS 3 lesions.

OBJECTIVE: To explore the feasibility and efficacy of clinical-imaging metrics in the diagnosis of prostate cancer (PCa) and clinically significant prostate cancer (csPCa) in prostate imaging-reporting and data system (PI-RADS) category 3 lesions. METHODS: A retrospective analysis was conducted on lesions diagnosed as PI-RADS 3. They were categorized into benign, non-csPCa and csPCa groups. Apparent diffusion coefficient (ADC), T2-weighted imaging signal intensity (T2WISI), coefficient of variation of ADC and T2WISI, prostate-specific antigen density (PSAD), ADC density (ADCD), prostate-specific antigen lesion volume density (PSAVD) and ADC lesion volume density (ADCVD) were measured and calculated. Univariate and multivariate analyses were used to identify risk factors associated with PCa and csPCa. Receiver operating characteristic curve (ROC) and decision curves were utilized to assess the efficacy and net benefit of independent risk factors. RESULTS: Among 202 patients, 133 had benign prostate disease, 25 non-csPCa and 44 csPCa. Age, PSA and lesion location showed no significant differences (P > 0.05) among the groups. T2WISI and coefficient of variation of ADC (ADCcv) were independent risk factors for PCa in PI-RADS 3 lesions, yielding an area under the curve (AUC) of 0.68. ADC was an independent risk factor for csPCa in PI-RADS 3 lesions, yielding an AUC of 0.65. Decision curve analysis showed net benefit for patients at certain probability thresholds. CONCLUSIONS: T2WISI and ADCcv, along with ADC, respectively showed considerable promise in enhancing the diagnosis of PCa and csPCa in PI-RADS 3 lesions.

Temporary alleviation of MAPK by arbutin alleviates oxidative damage in the retina and ARPE-19 cells.

Dry age-related macular degeneration (AMD) is one of the main diseases that causes blindness in humans, and the number of cases is increasing yearly. However, effective treatments are unavailable, and arbutin (ARB) has been reported to have antioxidant, anti-inflammatory, and anti-aging effects in other age-related diseases. However, whether ARB can be used to treat dry AMD remains unknown. To explore the therapeutic potential and molecular mechanism of arbutin in the treatment of dry AMD. MTT assays, reactive oxygen species (ROS) production assays, flow cytometry assays, qPCR and western blotting were used to assess the impact of ARB on human RPECs induced by H2O2. A transcriptome sequencing assay was used to further explore how ARB acts on human RPECs treated with H2O2. Hematoxylin and eosin (H&E) staining and total antioxidant capacity (T-AOC) assays were used to observe the impact of ARB on mouse retina induced by sodium iodate. ARB counteracted the H2O2-induced reduction in human RPECs viability, ARB reversed H2O2-induced cellular ROS production by increasing the expression of antioxidant-related genes and proteins, ARB also reversed H2O2-induced cell apoptosis by altering the expression of apoptosis-related genes and proteins. Transcriptome sequencing and western blotting showed that ARB reduced ERK1/2 and P-38 phosphorylation to prevent H2O2-induced oxidation damage. The in vivo experiments demonstrated that ARB protected against retinal morphology injury in mice, increased serum T-AOC levels and increased antioxidant oxidase gene expression levels in the mouse retina induced by sodium iodate. We concluded that ARB reversed the H2O2-induced decrease in human RPECs viability through the inhibition of ROS production and apoptosis. The ERK1/2 and P38 MAPK signaling pathways may mediate this process. ARB maintained retinal morphology, increased serum T-AOC level and improved the expression of antioxidant oxidase genes in mice.

Breaking Down the Barriers of Drug Resistance and Corneal Permeability with Chitosan-Poly(ethylene glycol)-LK13 Peptide Conjugate to Combat Fungal Keratitis.

Fungal keratitis (FK) is a leading cause of preventable blindness and eye loss. The poor antifungal activity, increased drug resistance, limited corneal permeability, and unsatisfactory biosafety of conventional antifungal eye drops are among the majority of the challenges that need to be addressed for currently available antifungal drugs. Herein, this study proposes an effective strategy that employs chitosan-poly(ethylene glycol)-LK13 peptide conjugate (CPL) in the treatment of FK. Nanoassembly CPL can permeate the lipophilic corneal epithelium in the transcellular route, and its hydrophilicity surface is a feature to drive its permeability through hydrophilic stroma. When encountering fungal cell membrane, CPL dissembles and exposes the antimicrobial peptide (LK13) to destroy fungal cell membranes, the minimum inhibitory concentration values of CPL against Fusarium solani (F. solani) are always not to exceed 8 µg peptide/mL before and after drug resistance induction. In a rat model of Fusarium keratitis, CPL demonstrates superior therapeutic efficacy than commercially available natamycin ophthalmic suspension. This study provides more theoretical and experimental supports for the application of CPL in the treatment of FK.

Recent Developments and Challenges in Solid-Contact Ion-Selective Electrodes.

Solid-contact ion-selective electrodes (SC-ISEs) have the advantages of easy miniaturization, even chip integration, easy carrying, strong stability, and more favorable detection in complex environments. They have been widely used in conjunction with portable, wearable, and intelligent detection devices, as well as in on-site analysis and timely monitoring in the fields of environment, industry, and medicine. This article provides a comprehensive review of the composition of sensors based on redox capacitive and double-layer capacitive SC-ISEs, as well as the ion-electron transduction mechanisms in the solid-contact (SC) layer, particularly focusing on strategies proposed in the past three years (since 2021) for optimizing the performance of SC-ISEs. These strategies include the construction of ion-selective membranes, SC layer, and conductive substrates. Finally, the future research direction and possibilities in this field are discussed and prospected.

Corrosion-Induced Cracking Model of Concrete Considering a Transverse Constraint.

The performance of corrosion-induced cracking of reinforced concrete members under transverse constraints was studied. Based on the theory of elastic-plastic mechanics and the hypothesis of uniform corrosion of a steel bar, a three-layer hollow cylinder model was established to predict the critical corrosion of the steel bar at the time of the cracking of the concrete cover. Taking the constraint of stirrups on surrounding concrete into consideration, it can be used to predict the corrosion rate of members with stirrups at the time of the cracking of the concrete cover, which further expands the application range of the corrosion-induced cracking models of concrete. On this basis, the critical corrosion rate of concrete under different stirrup ratios at the time of cracking was measured. The calculated results of the model are in accordance with experimental data. For corner steel bars, when the stirrup spacing is less than 100 mm, the existence of stirrups can effectively delay the occurrence of rust expansion cracks and enhance the durability of the structure. On the basis of this study, the problem of corrosion expansion and cracking of the concrete cover caused by non-uniform corrosion of steel bars along longitudinal and radial directions needs to be further studied in the future.

Resilience mechanisms of Trichopria drosophilae (Hymenoptera: Diapriinae) under global extreme cooling: insights into parasitic response and physiological adaptation.

Global climate warming and frequent extreme low-temperature events have made it essential to investigate the impact of low temperatures on parasitic wasps to protect and strengthen farmland biodiversity, which in turn enhances the biological control potential of natural enemies such as parasitic wasps. We systematically examined how low-temperature stress affects the parasitic functional response of Trichopria drosophilae to Drosophila suzukii (Diptera: Drosophilidae) pupae. Our findings indicate that the parasitic behavior of T. drosophilae towards D. suzukii pupae aligns with the Holling II functional response model following exposure to different temperatures. Within the temperature range of 8 °C to -8 °C, lower temperatures correlated decreased instantaneous attack rate of T. drosophilae and an increase in processing time. The search constant Q initially increased and then decreased with declining temperatures. Short-term low-temperature stress negatively impacted the parasitic and searching abilities of T. drosophilae but did not alter its parasitic functional response model. Notably, short-term low-temperature stress had minimal effects on the water content, protein content, and total sugar content of male and female T. drosophilae adults. However, as temperatures decreased, the activities of key enzymes, including GAPDH, SOD, T-AOC, and malondialdehyde (MDA), exhibited an initial increase followed by a decrease. Conversely, the activities of LDH and HOAD decreased, while the activities of CAT and POD increased. Further study on the effect of short-term low temperature on T. drosophilae can provide a research basis for the large-scale production and low-temperature refrigeration technology of T. drosophilae, and provide a scientific basis for its efficient use in the field.

Molecularly specific detection towards trace nitrogen dioxide by utilizing Schottky-junction-based Gas Sensor.

Trace NO2 detection is essential for the production and life, where the sensing strategy is appropriate for rapid detection but lacks molecular specificity. This investigation proposes a sensing mechanism dominated by surface-scattering to achieve the molecularly-specific detection. Two-dimensional Bi2O2Se is firstly fabricated into a Schottky-junction-based gas-sensor. Applied with an alternating excitation, the sensor simultaneously outputs multiple response signals (i.e., resistance, reactance, and the impedance angle). Their response times are shorter than 200 s at room temperature. In NO2 sensing, these responses present the detection limit in ppt range and the sensitivity is up to 16.8 %·ppb-1. This NO2 sensitivity presents orders of magnitude higher than those of the common gases within the exhaled breath. The impedance angle is involved in the principle component analysis together with the other two sensing signals. Twelve kinds of typical gases containing NO2 are acquired with molecular characteristics. The change in dipole moment of the target molecule adsorbed is demonstrated to correlate with the impedance angle via surface scattering. The proposed mechanism is confirmed to output ultra-sensitive sensing responses with the molecular characteristic.

Synthesis and biological evaluation of chrysin derivatives containing α-lipoic acid for the treatment of inflammatory bowel disease.

This study introduces newly discovered chrysin derivatives that show potential as candidate molecules for treating inflammatory bowel disease (IBD). Compound 4b, among the synthesized compounds, displayed significant inhibitory effects on monocyte adhesion to colon epithelium induced by TNF-α, with an IC50 value of 4.71 µM. Further mechanistic studies demonstrated that 4b inhibits the production of reactive oxygen species (ROS) and downregulates the expression of ICAM-1 and MCP-1, key molecules involved in monocyte-epithelial adhesion, as well as the transcriptional activity of NF-κB. In vivo experiments have shown that compound 4b exhibits a dose-dependent inhibition of 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats, thereby validating its effectiveness as a colitis inhibitor in animal models. These results indicate that 4b shows considerable promise as a therapeutic agent for managing IBD.

Microfluidic sweat patch based on capillary force and evaporation pump for real-time continuous sweat analysis.

In addition to the common blood and urine, fresh sweat contains a diverse range of physiological indicators that can effectively reflect changes in the body's state. Wearable sweat sensors are crucial for understanding human physiological health; however, real-time in situ measurement of multiple biomarkers in sweat remains a significant challenge. Here, we propose a wearable microfluidic patch featuring an integrated microfluidic channel and evaporation pump for accelerated and continuous sweat collection, eliminating the need for additional sweat storage cavities that typically impede real-time detection. Capillary forces are harnessed to facilitate the rapid flow of sweat through the detection area, while an evaporation pump based on porous laser-induced graphene enhances sweat evaporation. The synergistic integration of these two components enables an uninterrupted flow of fresh sweat within the patch, ensuring real-time monitoring. The influence of channel size parameters on sweat flow velocity is analyzed, and the optimal width-to-height ratio for achieving the desired flow velocity is determined. By implementing a multi-channel parallel design with chamfering, liquid flow resistance is effectively reduced. Furthermore, the patch integrates sensor modules for sodium ion, chloride ion, glucose, and pH value measurements, ensuring excellent sealing and stability of the assembled system. This work presents a simplified approach to developing wearable sweat sensors that hold the potential for health monitoring and disease diagnosis.

Research on Adaptive Grasping with a Prosthetic Hand Based on Perceptual Information on Hardness and Surface Roughness.

In order to solve the problems of methods that use a single form of sensing, the ease of causing deformation damage to the targets with a low hardness during grasping, and the slow sliding inhibition of a prosthetic hand when the grasping target slides, which are problems that exist in most current intelligent prosthetic hands, this study introduces an adaptive control strategy for prosthetic hands based on multi-sensor sensing. Using a force-sensing resistor (FSR) to collect changes in signals generated after contact with a target, a prosthetic hand can classify the target's hardness level and adaptively provide the desired grasping force so as to reduce the deformation of and damage to the target in the process of grasping. A fiber-optic sensor collects the light reflected by the object to identify its surface roughness, so that the prosthetic hand adaptively adjusts the sliding inhibition method according to the surface roughness information to improve the grasping efficiency. By integrating information on the hardness and surface roughness of the target, an adaptive control strategy for a prosthetic hand is proposed. The experimental results showed that the adaptive control strategy was able to reduce the damage to the target by enabling the prosthetic hand to achieve stable grasping; after grasping the target with an initial force and generating sliding, the efficiency of slippage inhibition was improved, the target could be stably grasped in a shorter time, and the hardness, roughness and weight ranges of targets that could be grasped by the prosthetic hand were enlarged, thus improving the success rate of stable grasping under extreme conditions.

Genetic characterization of the first Deltacoronavirus from wild birds around Qinghai Lake.

Deltacoronavirus, widely distributed among pigs and wild birds, pose a significant risk of cross-species transmission, including potential human epidemics. Metagenomic analysis of bird samples from Qinghai Lake, China in 2021 reported the presence of Deltacoronavirus. A specific gene fragment of Deltacoronavirus was detected in fecal samples from wild birds at a positive rate of 5.94% (6/101). Next-generation sequencing (NGS) identified a novel Deltacoronavirus strain, which was closely related to isolates from the United Arab Emirates (2018), China (2022), and Poland (2023). Subsequently the strain was named A/black-headed gull/Qinghai/2021(BHG-QH-2021) upon confirmation of the Cytochrome b gene of black-headed gull in the sample. All available genome sequences of avian Deltacoronavirus, including the newly identified BHG-QH-2021 and 5 representative strains of porcine Deltacoronavirus (PDCoV), were classified according to ICTV criteria. In contrast to Coronavirus HKU15, which infects both mammals and birds and shows the possibility of cross-species transmission from bird to mammal host, our analysis revealed that BHG-QH-2021 is classified as Putative species 4. Putative species 4 has been reported to infect 5 species of birds but not mammals, suggesting that cross-species transmission of Putative species 4 is more prevalent among birds. Recombination analysis traced BHG-QH-2021 origin to dut148cor1 and MW01_1o strains, with MW01_1o contributing the S gene. Surprisingly, SwissModle prediction showed that the optimal template for receptor-binding domain (RBD) of BHG-QH-2021 is derived from the human coronavirus 229E, a member of the Alphacoronavirus, rather than the anticipated RBD structure of PDCoV of Deltacoronavirus. Further molecular docking analysis revealed that substituting the loop 1-2 segments of HCoV-229E significantly enhanced the binding capability of BHG-QH-2021 with human Aminopeptidase N (hAPN), surpassing its native receptor-binding domain (RBD). Most importantly, this finding was further confirmed by co-immunoprecipitation experiment that loop 1-2 segments of HCoV-229E enable BHG-QH-2021 RBD binding to hAPN, indicating that the loop 1-2 segment of the RBD in Putative species 4 is a probable key determinant for the virus ability to spill over into humans. Our results summarize the phylogenetic relationships among known Deltacoronavirus, reveal an independent putative avian Deltacoronavirus species with inter-continental and inter-species transmission potential, and underscore the importance of continuous surveillance of wildlife Deltacoronavirus.

Long-term soil warming changes the profile of primary metabolites in fine roots of Norway spruce in a temperate montane forest.

Climate warming poses major threats to temperate forests, but the response of tree root metabolism has largely remained unclear. We examined the impact of long-term soil warming (>14 years, +4°C) on the fine root metabolome across three seasons for 2 years in an old spruce forest, using a liquid chromatography-mass spectrometry platform for primary metabolite analysis. A total of 44 primary metabolites were identified in roots (19 amino acids, 12 organic acids and 13 sugars). Warming increased the concentration of total amino acids and of total sugars by 15% and 21%, respectively, but not organic acids. We found that soil warming and sampling date, along with their interaction, directly influenced the primary metabolite profiles. Specifically, in warming plots, concentrations of arginine, glycine, lysine, threonine, tryptophan, mannose, ribose, fructose, glucose and oxaloacetic acid increased by 51.4%, 19.9%, 21.5%, 19.3%, 22.1%, 23.0%, 38.0%, 40.7%, 19.8% and 16.7%, respectively. Rather than being driven by single compounds, changes in metabolite profiles reflected a general up- or downregulation of most metabolic pathway network. This emphasises the importance of metabolomics approaches in investigating root metabolic pathways and understanding the effects of climate change on tree root metabolism.

Randomized, blind, controlled phase III clinical trial: Assessing the immunogenicity and safety of freeze-dried human rabies vaccine (vero cell) with a 4-dose regimen (2-1-1) in a 10-60 year-old demographic.

OBJECTIVE: The aim of this study is to demonstrate that the freeze-dried human rabies vaccine (Vero cell), administered in a four-dose schedule (2-1-1) to the 10-60 years old population, has immunogenicity that is not inferior to the approved five-dose schedule and similar vaccines with a four-dose schedule, and to evaluate its safety. METHOD: A total of 1800 individuals were enrolled and divided into three groups: four-dose test group, four-dose control group, and five-dose control group. The rabies virus neutralizing antibodies were measured using the Rapid Fluorescent Focus Inhibition Test to assess immunogenicity, and the incidence of adverse events and serious adverse events were statistically analyzed. RESULTS: The seroconversion rates 14 days after the first dose and 14 days after the complete course of vaccination were 100% in all three groups. The antibody GMC of the four-dose test group was higher than that of the five-dose control group, but slightly lower than the four-dose control group. Seven days after the first dose, both four-dose regimen groups showed higher seroconversion rates and antibody GMCs compared to the five-dose regimen group, proving that the immunogenic effect of the four-dose regimen seven days post-first vaccination is superior to the five-dose regimen. The overall incidence of adverse events showed no significant difference between the four-dose test group and the five-dose control group, but was significantly lower in the four-dose test group compared to the four-dose control group. CONCLUSION: The vaccine in the four-dose test group is equivalent in immunogenic effect to the four-dose control group vaccine and superior to the five-dose control group vaccine; the safety of the vaccine in the four-dose test group is equivalent to the five-dose control group vaccine and superior to the four-dose control group vaccine. CLINICALTRIALS: gov number: NCT05549908.

Endovascular thrombectomy versus medical management on outcomes with infarct volumes more than 70 mL.

OBJECTIVE: Endovascular thrombectomy (EVT) in patients with large infarct volume remains controversial. The aim of this study is to compare clinical outcomes between EVT and medical management in acute large vessel occlusion with infarct volumes larger than 70 mL on diffusion-weighted magnetic resonance imaging (DWI). METHODS: A prospective observational cohort study was conducted, including patients with anterior cerebral circulation occlusion due to ischemic stroke with infarct volumes larger than 70 mL within 24 h of onset between July 2018 and June 2023. Eligible patients were divided into two groups: the EVT group and the medical management (non-EVT) group. The main outcomes were functional independence and mortality at 90 days. To assess clinical endpoints, we selected variables including age, NIHSS score, infarct volume, and occlusion location for 1:1 propensity score (PS) matching and PS adjustment using inverse probability of treatment weighting (IPTW). RESULTS: Among the 131 identified patients (mean [SD] age, 69.9 [13.7] years; 58 female), the median infarct volume was 123.6 mL. Of these patients, 75 (57.3%) underwent EVT. After PS adjustment, EVT was not associated with functional independence (10.9% vs. 10.9%; p = 1.000) or mortality (43.5% vs. 47.8%; p = 0.675). Additionally, after PS adjustment using IPTW, EVT was also not associated with a functional independence (15.8% vs. 13.7%; p = 0.767) or mortality (46.8% vs. 44.0%; p = 0.762). CONCLUSION: This study provides real-world evidence regarding infarct volumes larger than 70 mL, indicating that EVT does not provide benefits compared to medical management alone when considering age, NIHSS score, infarct volume, and occlusion location.

The discovery of a potent PARP1 inhibitor Senaparib.

Poly (ADP-ribose) polymerases 1 (PARP1) is a critical enzyme involved in DNA damage repair. It belongs to a super family of proteins and catalyzes poly (ADP-ribosyl)ation (PARylation). PARP1 inhibitors are effective to treat tumors that have homologous recombination deficiency (HRD) such as the ones with BRCA1/2 mutations. The PARP1 inhibitors that have been approved by FDA inhibit both PARP1 and PARP2. PARP2 has also been suggested to have similar function in DNA repair as PARP1. In addition to inhibiting PARP1 enzymatic activities, PARP1 inhibitors also cause PARP1 enzyme to be "trapped" on DNA which leads to DNA replication fork to stall and eventually double-strand DNA breaks and cell death. Here, we report a PARP1 inhibitor, Senaparib, which has a novel chemical structure and high potency inhibiting PARP1/2 enzymes. Senaparib was highly potent in cell viability tests against tumor cells with BRCA1/2 mutations. It was efficacious in CDX and PDX xenograft models in tumor harboring BRCA1/2 mutations. In combination studies, Senaparib used with temozolomide (TMZ) had shown strong synergistic cytotoxicity in both in vitro and in vivo experiments. Senaparib represents a novel class of PARP1 inhibitors that can be used for the treatment of cancer. A phase III clinical study of Senaparib for maintenance treatment following first-line chemotherapy in patients with advanced ovarian cancer has met its primary endpoint, and a new drug application of Senaparib has been accepted by National Medical Products Administration (NMPA) of China for review.

Risk factors for ventricular arrhythmias after emergency percutaneous coronary intervention in elderly patients with acute myocardial infarction.

OBJECTIVE: To explore the risk factors for ventricular arrhythmia after percutaneous coronary intervention (PCI) in elderly patients with acute myocardial infarction (AMI). METHODS: A retrospective cohort of 201 elderly AMI patients who underwent PCI in the emergency department of No. 215 Hospital of Shaanxi Nuclear Industry from April 2020 to January 2023 was analyzed. The patients were randomly divided into a training set (n=134) for model development and a test set (n=67) for model validation. The training set was divided into a ventricular arrhythmia group (n=51) and a non-ventricular arrhythmia group (n=83), based on the occurrence of ventricular arrhythmia post-PCI. The factors affecting ventricular arrhythmias were analyzed by logistic regression and Lasso regression models. RESULTS: Lasso regression screened 12 characteristic factors at λ=0.1 se. In the training set, the area under the ROC curve (AUC) of the Lasso model for predicting ventricular arrhythmia was 0.954, which was significantly higher than 0.826 for the Logistic model (P < 0.001). In the test set, the AUC of the Lasso model was 0.962, which was also significantly higher than 0.825 for the Logistic model (P=0.003). CONCLUSION: Compared to the logistic regression model, the Lasso regression model can more accurately predict the occurrence of ventricular arrhythmia after PCI in elderly AMI patients. The Lasso regression model constructed in this study can provide a reference for the clinical identification of high-risk elderly AMI patients and the development of targeted monitoring and treatment.

MicroRNA-204-5p Attenuates Oxidative Stress, Apoptosis and Inflammation by Targeting TXNIP in Diabetic Cataract.

Diabetic cataract (DC) is a major cause of blindness in diabetic patients and it is characterized by early onset and rapid progression. MiR-204-5p was previously identified as one of the top five down-regulated miRNAs in human DC lens tissues. We aimed to determine the expression of miR-204-5p in human lens epithelial cells (HLECs) and explore its effects and mechanisms in regulating the progression of DC. The expression of miR-204-5p in the anterior capsules of DC patients and HLECs was examined by RT-qPCR. Bioinformatics tools were then used to identify the potential target of miR-204-5p. The relationship between miR-204-5p and the target gene was confirmed through a dual luciferase reporter assay. Additionally, the regulatory mechanism of oxidative stress, apoptosis, and inflammation in DC was investigated by overexpressing miR-204-5p using miR-204-5p agomir. The expression of miR-204-5p was downregulated in the anterior capsules of DC patients and HLECs. Overexpression of miR-204-5p reduced ROS levels, pro-apoptosis genes (Bid, Bax, caspase-3), and IL-1ß production in HG-treated HLECs. TXNIP was the direct target of miR-204-5p by dual luciferase reporter assay. Therefore, this study demonstrated that miR-204-5p effectively reduced oxidative damage, apoptosis, and inflammation in HLECs under HG conditions by targeting TXNIP. Targeting miR-204-5p could be a promising therapeutic strategy for the potential treatment of DC.

Integrated multi-omics analyses revealed the association between rheumatoid arthritis and colorectal cancer: MYO9A as a shared gene signature and an immune-related therapeutic target.

BACKGROUND: Our study aims to explore the relationship, shared gene signature, and the underlying mechanisms that connect rheumatoid arthritis (RA) to colorectal cancer (CRC). METHODS: Mendelian randomization (MR) analysis was conducted to assess the causality between RA and CRC. Summary statistic data-based Mendelian randomization (SMR) leveraging eQTL data was employed to identify the CRC-related causal genes. Integrated analyses of single-cell RNA sequencing and bulk RNA sequencing were employed to comprehensively investigate the shared gene signature and potential mechanisms underlying the pathogenesis of both RA and CRC. Predictive analysis of the shared hub gene in CRC immunotherapy response was performed. Pan-cancer analyses were conducted to explore the potential role of MYO9A in 33 types of human tumors. RESULTS: MR analysis suggested that RA might be associated with a slight increased risk of CRC (Odds Ratio = 1.04, 95% Confidence Interval = 1.01-1.07, P = 0.005). SMR analysis combining transcriptome analyses identified MYO9A as a causal gene in CRC and a shared gene signature in both RA and CRC. MYO9A may contribute to tumor suppression, while downregulation of MYO9A may impact CRC tumorigenesis by disrupting epithelial polarity and architecture, resulting in a worse prognosis in CRC. Additionally, MYO9A shows promise as a powerful predictive biomarker for cancer prognosis and immunotherapy response in CRC. Pan-cancer analyses demonstrated MYO9A may have a protective role in the occurrence and progression of various human cancers. CONCLUSION: RA might be associated with a slight increased risk of CRC. MYO9A is a shared gene signature and a potential immune-related therapeutic target for both CRC and RA. Targeting the MYO9A-mediated loss of polarity and epithelial architecture could be a novel therapeutic approach for CRC.

Investigation into the genotoxic impurity, 1-methyl-4-nitrosopiperazine, in rifampicin.

This study assessed the presence of the genotoxic impurity 1-methyl-4-nitrosopiperazine (MNP) in 27 batches of rifampicin capsules obtained from 11 manufacturers in China. While they were below the temporary limit of 5 ppm set by the US Food and Drug Administration, the observed levels (0.33-2.36 ppm) exceeded the acceptable threshold of 0.16 ppm. Building upon preliminary findings and degradation experiments, we concluded that MNP is a by-product of the oxidative degradation of rifampicin or is introduced via oxidation or nitrosation during the synthesis process involving 1-methyl-4-aminopiperazine. The pathways of MNP formation were confirmed in this study. Furthermore, we observed that the addition of antioxidants, sealed storage, and selection of dominant crystal forms can aid in controlling MNP levels.