The role of the ER stress sensor IRE1 in cardiovascular diseases.

Despite enormous advances in the treatment of cardiovascular diseases, including I/R injury and heart failure, heart diseases remain a leading cause of mortality worldwide. Inositol-requiring enzyme 1 (IRE1) is an evolutionarily conserved sensor endoplasmic reticulum (ER) transmembrane protein that senses ER stress. It manages ER stress induced by the accumulation of unfolded/misfolded proteins via the unfolded protein response (UPR). However, if the stress still persists, the UPR pathways are activated and induce cell death. Emerging evidence shows that, beyond the UPR, IRE1 participates in the progression of cardiovascular diseases by regulating inflammation levels, immunity, and lipid metabolism. Here, we summarize the recent findings and discuss the potential therapeutic effects of IRE1 in the treatment of cardiovascular diseases.

Muscularis macrophages controlled by NLRP3 maintain the homeostasis of excitatory neurons.

Peristaltic movements in gut are essential to propel ingested materials through the gastrointestinal tract. Intestinal resident macrophages play an important role in this physiological function through protecting enteric neurons. However, it is incompletely clear how individuals maintain the homeostasis of gut motility. Here we found that NLRP3 is a critical factor in controlling loss of muscularis resident macrophages (MMs), and demonstrate that MMs are involved in the homeostasis of excitatory neurons such as choline acetyltransferase (ChAT)+ and vesicular glutamate transporter 2 (VGLUT2)+ but not inhibitory neuronal nitric oxide synthase (nNOS)+ neurons. NLRP3 knockout (KO) mice had enhanced gut motility and increased neurons, especially excitatory ChAT+ and VGLUT2+ neurons. Single cell analyses showed that there had increased resident macrophages, especially MMs in NLRP3 KO mice. The MM proportion in the resident macrophages was markedly higher than those in wild-type (WT) or caspase 1/11 KO mice. Deletion of the MMs and transplantation of the NLRP3 KO bone marrow cells showed that survival of the gut excitatory ChAT+ and VGLUT2+ neurons was dependent on the MMs. Gut microbiota metabolites ß-hydroxybutyrate (BHB) could promote gut motility through protecting MMs from pyroptosis. Thus, our data suggest that MMs regulated by NLRP3 maintain the homeostasis of excitatory neurons.

Long-Term Exposure to Fine Particulate Matter and Fasting Blood Glucose and Diabetes in 20 Million Chinese Women of Reproductive Age.

OBJECTIVE: Evidence of the associations between fine particulate matter (PM2.5) and diabetes risk from women of reproductive age, in whom diabetes may have adverse long-term health effects for both themselves and future generations, remains scarce. We therefore examined the associations of long-term PM2.5 exposure with fasting blood glucose (FBG) level and diabetes risk in women of reproductive age in China. RESEARCH DESIGN AND METHODS: This study included 20,076,032 women age 20-49 years participating in the National Free Preconception Health Examination Project in China between 2010 and 2015. PM2.5 was estimated using a satellite-based model. Multivariate linear and logistic regression models were used to examine the associations of PM2.5 exposure with FBG level and diabetes risk, respectively. Diabetes burden attributable to PM2.5 was estimated using attributable fraction (AF) and attributable number. RESULTS: PM2.5 showed monotonic relationships with elevated FBG level and diabetes risk. Each interquartile range (27 µg/m3) increase in 3-year average PM2.5 concentration was associated with a 0.078-mmol/L (95% CI 0.077, 0.079) increase in FBG and 18% (95% CI 16%, 19%) higher risk of diabetes. The AF attributed to PM2.5 exposure exceeding 5 µg/m3 was 29.0% (95% CI 27.5%, 30.5%), corresponding to an additional 78.6 thousand (95% CI 74.5, 82.6) diabetes cases. Subgroup analyses showed more pronounced diabetes risks in those who were overweight or obese, age >35 years, less educated, of minority ethnicity, registered as a rural household, and residing in western China. CONCLUSIONS: We found long-term PM2.5 exposure was associated with higher diabetes risk in women of reproductive age in China.

Biodistribution and preclinical safety profile of legubicin: A novel conjugate of doxorubicin and a legumain-cleavable peptide linker.

Legubicin is a novel conjugate of doxorubicin and a legumain-cleavable peptide linker. It has been developed to ameliorate the side effects of doxorubicin. Biodistribution in tumor-bearing mice, acute tolerance, and potential systemic toxic effects in Sprague-Dawley rats and beagle dogs of legubicin were assessed. Legubicin exists mainly as a protein complex in plasma after entering the circulation. Compared with conventional doxorubicin at an equal molar dose in mice, we found higher exposure to doxorubicin in tumor (approximately 1.7-fold increase) while lower exposure in normal tissues (an ~3.26-, 3.46-, and 1.29-fold reduction in heart, kidney, and plasma, respectively) in tumor-bearing mice after intravenous injection of legubicin. The acute maximum tolerance dose (MTD) of legubicin was >16 mg/kg doxorubicin equivalent in female rats, 11 mg/kg doxorubicin equivalent in male rats (LD50 of conventional doxorubicin is 10.51 mg/kg), and >8 mg/kg doxorubicin equivalent in dogs (MTD of conventional doxorubicin is 1.5 mg/kg). Four-week repeat-dose toxicity studies of intravenous legubicin were conducted in rats (5, 10, and 25 mg/kg/dose once weekly) and dogs (3/1.5, 10/5, and 20/10 mg/kg/dose once weekly); the dose levels were reduced from the second dose due to intolerable legubicin-associated toxicity at 20 mg/kg. Major organs of toxicity included the gastrointestinal tract, lymphoid and hematopoietic organs, kidney, skin, liver, reproductive organs, and peripheral nerves, which are all associated with doxorubicin. However, cardiotoxicity was only noted at MTD dose levels. Altogether, our results confirm an improved safety profile of legubicin over conventional doxorubicin and support its clinical benefit for treating cancer.

Prognosis prediction models for post-stroke depression: a protocol for systematic review, meta-analysis, and critical appraisal.

INTRODUCTION: Post-stroke depression (PSD) is a prevalent complication that has been shown to have a negative impact on rehabilitation outcomes and quality of life and poses a significant risk for suicidal intention. However, models for discriminating and predicting PSD in stroke survivors for effective secondary prevention strategies are inadequate as the pathogenesis of PSD remains unknown. Prognostic prediction models that exhibit greater rule-in capacity have the potential to mitigate the issue of underdiagnosis and undertreatment of PSD. Thus, the planned study aims to systematically review and critically evaluate published studies on prognostic prediction models for PSD. METHODS AND ANALYSIS: A systematic literature search will be conducted in PubMed and Embase through Ovid. Two reviewers will complete study screening, data extraction, and quality assessment utilizing appropriate tools. Qualitative data on the characteristics of the included studies, methodological quality, and the appraisal of the clinical applicability of models will be summarized in the form of narrative comments and tables or figures. The predictive performance of the same model involving multiple studies will be synthesized with a random effects meta-analysis model or meta-regression, taking into account heterogeneity. ETHICS AND DISSEMINATION: Ethical approval is considered not applicable for this systematic review. Findings will be shared through dissemination at academic conferences and/or publication in peer-reviewed academic journals. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023388548.

Air pollutants, genetic susceptibility, and incident schizophrenia in later life: A prospective study in the UK Biobank.

OBJECTIVE: Air pollution has been linked to multiple psychiatric disorders, but little is known on its long-term association with schizophrenia. The interaction between air pollution and genetic susceptibility on incident schizophrenia has never been reported. We aimed to explore the associations between long-term air pollution exposure and late-onset schizophrenia and evaluate whether genetic susceptibility could modify the association. METHODS: This population-based prospective cohort study included 437,802 middle-aged and elderly individuals free of schizophrenia at baseline in the UK Biobank. Land use regression models were applied in the estimation of the annual average concentrations of nitrogen dioxide (NO2), nitrogen oxides (NOx), fine particulate matter (PM2.5), and inhalable particulate matter (PM10) at residence. The associations between air pollutants and schizophrenia were evaluated by using Cox proportional hazard models. A polygenic risk score of schizophrenia was constructed for exploring potential interaction of air pollutants with genetic susceptibility. RESULTS: An interquartile range increase in PM2.5, PM10, NO2, and NOx was associated with the hazard ratios (HR) for incident schizophrenia at 1.19, 1.16, 1.22, and 1.09, respectively. The exposure-response curves for the association of air pollution with incident schizophrenia were approximately linear. There are additive interactions of air pollution score (APS), PM10, NO2, and NOx with genetic risk. Specifically, compared with participants with low genetic susceptibility and low APS, the HR was 3.23 for individuals with high genetic risk and high APS, among which 0.49 excess risk could be attributed to the additive interaction, accounting for 15 % of the schizophrenia risk. CONCLUSION: This large-scale, prospective cohort study conveys the first-hand evidence that long-term air pollution exposure could elevate schizophrenia incidence in later life, especially for individuals with higher genetic risks. The findings highlight the importance of improving air quality for preventing the late-onset schizophrenia in an aging era, especially among those with high genetic risks.

Differentiating the impact of fine and coarse particulate matter on cause-specific cerebrovascular mortality: An individual-level, case-crossover study.

BACKGROUND AND OBJECTIVES: Many studies suggested that short-term exposure to fine particulate matter (PM2.5) and coarse particulate matter (PM2.5-10) was linked to elevated risk of cerebrovascular disease. However, little is known about the potentially differential effects of PM2.5 and PM2.5-10 on various types of cerebrovascular disease. METHODS: We collected individual cerebrovascular death records for all residents in Shanghai, China from 2005 to 2021. Residential daily air pollution data were predicted from a satellite model. The associations between particulate matters (PM) and cerebrovascular mortality were investigated by an individual-level, time-stratified, case-crossover design. The data was analyzed by the conditional logistic regression combined with the distributed lag model with a maximum lag of 7 days. Furthermore, we explored the effect modifications by sex, age and season. RESULTS: A total of 388,823 cerebrovascular deaths were included. Monotonous increases were observed for mortality of all cerebrovascular diseases except for hemorrhagic stroke. A 10 µg/m3 rise in PM2.5 was related to rises of 1.35% [95% confidence interval (CI): 1.04%, 1.66%] in mortality of all cerebrovascular diseases, 1.84% (95% CI: 1.25%, 2.44%) in ischemic stroke, 1.53% (95% CI: 1.07%, 1.99%) in cerebrovascular sequelae and 1.56% (95% CI: 1.08%, 2.05%) in ischemic stroke sequelae. The excess risk estimates per each 10 µg/m3 rise in PM2.5-10 were 1.47% (95% CI: 1.10%, 1.84%), 1.53% (95% CI: 0.83%, 2.24%), 1.93% (95% CI: 1.38%, 2.49%) and 2.22% (95% CI: 1.64%, 2.81%), respectively. The associations of both pollutants with all cerebrovascular outcomes were robust after controlling for co-pollutants. The associations were greater in females, individuals > 80 years, and during the warm season. CONCLUSIONS: Short-term exposures to both PM2.5 and PM2.5-10 may independently increase the mortality risk of cerebrovascular diseases, particularly of ischemic stroke and stroke sequelae.

Mechanistic insights into cardiovascular effects of ultrafine particle exposure: A longitudinal panel study.

BACKGROUND: Ultrafine particle (UFP) has been linked with higher risks of cardiovascular diseases; however, the biological mechanisms remain to be fully elucidated. OBJECTIVES: This study aims to investigate the cardiovascular responses to short-term UFP exposure and the biological pathways involved. METHODS: A longitudinal panel study was conducted among 32 healthy, non-smoking young adults in Shanghai, China, who were engaged in five rounds of follow-ups between December 2020 and November 2021. Individual exposures were calculated based on the indoor and outdoor real-time measurements. Blood pressure, arterial stiffness, targeted biomarkers, and untargeted proteomics and metabolomics were examined during each follow-up. Linear mixed-effect models were applied to analyze the exposure and health data. The differential proteins and metabolites were used for pathway enrichment analyses. RESULTS: Short-term UFP exposure was associated with significant increases in blood pressure and arterial stiffness. For example, systolic blood pressure increased by 2.10 % (95 % confidence interval: 0.63 %, 3.59 %) corresponding to each interquartile increase in UFP concentrations at lag 0-3 h, while pulse wave velocity increased by 2.26 % (95 % confidence interval: 0.52 %, 4.04 %) at lag 7-12 h. In addition, dozens of molecular biomarkers altered significantly. These effects were generally present within 24 h after UFP exposure, and were robust to the adjustment of co-pollutants. Molecular changes detected in proteomics and metabolomics analyses were mainly involved in systemic inflammation, oxidative stress, endothelial dysfunction, coagulation, and disturbance in lipid transport and metabolism. DISCUSSION: This study provides novel and compelling evidence on the detrimental subclinical cardiovascular effects in response to short-term UFP exposure. The multi-omics profiling further offers holistic insights into the underlying biological pathways.

Quantification of the Heat-Related Risk and Burden of Hospitalizations for Cause-Specific Injuries and Contribution of Human-Induced Climate Change: A Time-Stratified Case-Crossover Study in China.

BACKGROUND: Although ambient temperature has been linked with injury incidence, there have been few nationwide studies to quantify the temperature-related risk and burden of cause-specific injury hospitalizations. Additionally, the impact of human-induced climate change to injury burden remains unknown. OBJECTIVES: Our objectives are to examine the associations between ambient temperature and injury hospitalizations from various causes and to quantify the contribution of human-induced warming to the heat-related burden. METHODS: We collected injury hospitalization data from a nationwide hospital-based registry in China during 2000-2019. Using a time-stratified case-crossover design, we investigated the associations between daily mean temperature (°C) and cause-specific injury hospitalizations. We also quantified the burden of heat-related injuries under the scenarios with and without anthropogenic forcing, using the Detection and Attribution Model Intercomparison Project to assess the contribution of human-induced warming. RESULTS: Our study included a total of 988,087 patients with hospitalization records for injuries. Overall, compared to the temperature at minimum risk of hospitalization (-12.1°C), the relative risk of hospitalization at extreme hot temperature (30.8°C, 97.5th percentile) was 1.18 [95% confidence interval (CI): 1.14, 1.22], with an approximately linear association between temperature and hospitalization. Vulnerability to heat-related injuries was more pronounced among males, young (<18 years of age) or middle-aged (45-64 years of age) individuals, and those living in the North. The heat-related attributable fraction increased from 23.2% in the 2000s to 23.6% in the 2010s, with a corresponding increase in the contribution of human-induced change over time. In the 2010s, the heat-related attributable fractions for specific causes of injury ranged from 12.4% to 54.4%, with human-induced change accounting for 6.7% to 10.6% of the burden. DISCUSSION: This nationwide study presents new evidence of significant associations between temperature and cause-specific injury hospitalizations in China and highlights the increasing contribution of human-induced warming to the injury burden. https://doi.org/10.1289/EHP14057.

Endogenous iron-enriched biochar derived from steel mill wastewater sludge for tetracycline removal: Heavy metals stabilization, adsorption performance and mechanism.

Steel mill wastewater sludge, as an iron-enriched solid waste, was expected to be converted into iron-enriched biochar with acceptable environmental risk by pyrolysis. The purpose of our study was to evaluate the chemical speciation transformation of heavy metals in biochar under various pyrolysis temperatures and its reutilization for tetracycline (TC) removal. The experimental data indicated that pyrolysis temperature was a key factor affecting the heavy metals speciation and bioavailability in biochar, and biochar with pyrolysis temperature at 450 °C was the most feasible for reutilization without potential risk. The endogenous iron-enriched biochar (FSB450) showed highly efficient adsorption towards TC, and its maximum adsorption capacity could reach 240.38 mg g-1, which should be attributed to its excellent mesoporous structure, abundant functional groups and endogenous iron cycling. The endogenous iron was converted to a stable iron oxide crystalline phase (Fe3O4 and MgFe2O4) by pyrolysis, which underwent a valence transition to form a coordination complex with TC by electron shuttling in the FSB450 matrix. The study provides a win-win approach for resource utilization of steel wastewater sludge and treatment of antibiotic contamination in wastewater.

Stabilizing High-Voltage Performance of Nickel-Rich Cathodes via Facile Solvothermally Synthesized Niobium-Doped Strontium Titanate.

Ni-rich layered ternary cathodes are promising candidates thanks to their low toxic Co-content and high energy density (∼800 Wh/kg). However, a critical challenge in developing Ni-rich cathodes is to improve cyclic stability, especially under high voltage (>4.3 V), which directly affects the performance and lifespan of the battery. In this study, niobium-doped strontium titanate (Nb-STO) is successfully synthesized via a facile solvothermal method and used as a surface modification layer onto the LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode. The results exhibited that the Nb-STO modification significantly improved the cycling stability of the cathode material even under high-voltage (4.5 V) operational conditions. In particular, the best sample in our work could provide a high discharge capacity of ∼190 mAh/g after 100 cycles under 1 C with capacity retention over 84% in the voltage range of 3.0-4.5 V, superior to the pristine NCM811 (∼61%) and pure STO modified STO-811-600 (∼76%) samples under the same conditions. The improved electrochemical performance and stability of NCM811 under high voltage should be attributed to not only preventing the dissolution of the transition metals, further reducing the electrolyte's degradation by the end of charge, but also alleviating the internal resistance growth from uncontrollable cathode-electrolyte interface (CEI) evolution. These findings suggest that the as-synthesized STO with an optimized Nb-doping ratio could be a promising candidate for stabilizing Ni-rich cathode materials to facilitate the widespread commercialization of Ni-rich cathodes in modern LIBs.

Design and radiological confirmation of 3-column cortical bone trajectory in the lumbar spine.

OBJECTIVE: The aim of this study was to design a novel lumbar cortical bone trajectory (CBT) penetrating the anterior, middle, and posterior vertebral area using imaging; measure the relevant parameters to find theoretical parameters and screw placement possibilities; and investigate the optimal implantation trajectory of the CBT in patients with osteoporosis. METHODS: Three types of CBTs with appropriate lengths were selected to simulate screw placement using Mimics software. These CBTs were classified as the leading tip of the trajectory pointing to the posterior quarter area (original CBT [CBT-O]) and middle (novel CBT A [CBT-A]) and anterior quarter (novel CBT B [CBT-B]) of the superior endplate. The authors then measured the maximum screw diameter (MSD) and length (MSL), cephalad (CA) and lateral (LA) angles, and bone mineral density (Hounsfield unit [HU] values) of the planned novel 3-column CBT screw placements. The differences in the parameters of the novel CBTs, the percentages of successfully planned CBT screws, and the factors that influenced the successful planning of 3-column CBT screws were analyzed. RESULTS: Three-column CBT screws were successfully designed in all segments of the lumbar spine. The success rate of the 3-column CBT planned screws was 72.25% (83.25% for CBT-A and 61.25% for CBT-B). From the CBT-O type, to the CBT-A type, to the CBT-B type, the LA, CA, and MSD of the novel CBT screws decreased with increasing trajectory length. The HU values of the three types of trajectories were all significantly higher than that of the traditional pedicle screw trajectory (p < 0.001). The main factor affecting successful planning of the 3-column CBT screw was pedicle width. CONCLUSIONS: Moderating adjustment of the original screw parameters by reducing LAs and CAs to penetrate the anterior, middle, and posterior columns of the vertebral body using the 3-column CBT screw is feasible, especially in the lower lumbar spine.

Nasal Staphylococcus aureus Carriage and Antimicrobial Resistance Profiles Among Community-Dwelling Adults in Jiangsu, China.

INTRODUCTION: Persistent nasal carriage has been associated with Staphylococcus aureus infection. Previous S. aureus studies in Asia have primarily focused on clinical patients, providing limited information on persistent nasal carriage among the general adult population. METHODS: This study examined 143 healthy adults in a community in Jiangsu, China. Nasal swab samples were collected 10 times. The colonization status was identified using SPA typing. We also determined antimicrobial susceptibility, genotype, and genomic characteristics of S. aureus. RESULTS: The prevalence of S. aureus nasal carriage among the community individuals was on average 16.78%. The carriage rates of methicillin-resistant S. aureus and multidrug-resistant S. aureus were 6.29% and 7.69%, respectively. We identified 8.39% persistent carriers, 39.16% intermittent carriers, and 52.45% noncarriers. Furthermore, family members displayed concordance in terms of genotype and genomic characteristics. CONCLUSION: Persistent nasal sampling captured intermittent carriers that were missed during short-term sampling, thus highlighting the necessity for regular community testing. SPA typing can serve as a rapid method for determining S. aureus colonization. The potential for intrafamilial transmission of S. aureus is evident, with persistent carriers being the most probable source of infection.

Single-Cell Data Analysis Reveals Critical Hepatic Cells Subpopulations in the Progression of Non-alcoholic Fatty Liver Disease to Non-Alcoholic Steatohepatitis.

AIMS: The aim of this study was to reveal the hepatic cell landscape and function in the progression of NAFLD to NASH. BACKGROUND: Non-alcoholic steatohepatitis (NASH) is the progressive form and turning point of nonalcoholic fatty liver disease (NAFLD), which severely causes irreversible cirrhosis as well as hepatocellular carcinoma. The mechanism underlying the progression of NAFLD to NASH has not been revealed. Unraveling the mechanism of action of NAFLD-NASH is an important goal in improving the survival of patients with liver disease. OBJECTIVE: The aim of this study is to discover heterogeneous hepatic cells during the progression of NAFLD to NASH. METHODS: Single-nucleus RNA-seq (snRNA-seq) data containing NASH in NAFLD samples were obtained from the Gene Expression Omnibus (GEO) database. Cell types in liver tissues from NASH and NAFLD were identified after dimensionality reduction analysis, cluster analysis, and cell annotation. The cell pathways in which differences existed were identified by analyzing metabolic pathways in Hepatic cells. We also identified cell subpopulations in Hepatic cells. The developmental trajectories of Hepatic cells were characterized by pseudotime trajectory analysis. Single-cell regulatory network inference and clustering analysis identified key transcription factors and gene regulatory networks in Hepatic cells. Moreover, cell communication analysis determined the potential interactions between Hepatic cells and immune cells, and heapatic stellate cells. RESULTS: Seven cell types were identified in NAFLD and NASH. The proportion of Hepatic cells was lower in NASH and showed greater energy metabolism and glucose metabolism activity. Hepatic cells exhibited heterogeneity, showing two cell subpopulations, Hepatic cells 1 and Hepatic cells 2. Dysregulation of lipid metabolism in Hepatic Cell 2 resulted in lipid accumulation in the liver, which might be involved in the progression of NAFLD. Four key transcription factors, BHLHE40, NFEL2L, RUNX1, and INF4A, were primarily found in Hepatic cells 2. The transcription factors within the hepatic cells 2 subpopulation mainly regulated genes related to lipid metabolism, energy metabolism, and inflammatory response. The cell communication analysis showed that hepatocyte interactions with immune cells were associated with inflammatory responses, while interactions with hepatic astrocytes were associated with liver injury and hepatocyte fibrosis. CONCLUSION: The hepatic cells 2 might promote the progression of NAFLD to NASH by regulating metabolic activity, which might contribute to liver injury through inflammation.

Enhanced Piezocatalytic Performance of Li-doped BaTiO3 Through a Facile Sonication-Assisted Precipitation Approach.

Piezocatalysis-induced dye degradation has garnered significant attention as an effective method for addressing wastewater treatment challenges. In our study, we employed a room-temperature sonochemical method to synthesize piezoelectric barium titanate nanoparticles (BaTiO3: BTO) with varying levels of Li doping. This approach not only streamlined the sample preparation process but also significantly reduced the overall time required for synthesis, making it a highly efficient and practical method. One of the key findings was the exceptional performance of the Li-doped BTO nanoparticles. With 20 mg of Li additive, we achieved 90% removal of Rhodamine B (RhB) dye within a relatively short timeframe of 150 minutes, all while subjecting the sample to ultrasonic vibration. This rapid and efficient dye degradation was further evidenced by the calculated kinetic rate constant, which indicated seven times faster degradation rate compared to pure BTO. The enhanced piezoelectric performance observed in the Li-doped BTO nanoparticles can be attributed to the strategic substitution of Li atoms, which facilitated a more efficient transfer of charge charges at the interface. Overall, our study underscores the potential of piezocatalysis coupled with advanced materials like Li-doped BTO nanoparticles as a viable and promising solution for wastewater treatment, offering both efficiency and environmental sustainability.

Terahertz fingerprint reveals the effect of alcohols on sodium ions hydration shell.

Ion hydration plays a crucial role in numerous fundamental processes. Various spectroscopic methods are employed to investigate the slowing down of hydration bond dynamics in the proximity of both anions and cations. To date, most of these studies have primarily focused on the properties of binary systems. However, in comparison to ion-water binary systems, ternary systems that involve ions, water, and organic matter are more prevalent in nature and provide more realistic insights into biological processes. This study focuses on ion hydration in water and alcohol mixture using terahertz spectroscopy and x-ray diffraction (XRD). The results reveal a distinct behavior depending on the type of alcohol used. Specifically, the presence of both methanol and ethanol results in the disappearance of absorption peaks associated with NaCl hydrate at low temperatures. In contrast, tert-butanol does not exhibit such an effect, and isopropanol demonstrates a more complex response. By combining these terahertz spectroscopic findings with low-temperature XRD data, we gain insights into the formation, or lack thereof, of NaCl · 2H2O hydrate crystals. Crucially, our observations suggest a dominant correlation between the polarity of the alcohol molecules and its impact on the Na+ hydration. Strongly polar alcohols preferentially solvating the Na+ ion lead to the failure of hydrate formation, while weakly polar alcohols do not have this effect.

piR-1919609 Is an Ideal Potential Target for Reversing Platinum Resistance in Ovarian Cancer.

PURPOSE: PIWI-interacting RNAs (piRNAs) are a type of noncoding small RNA that can interact with PIWI-like RNA-mediated gene silencing (PIWIL) proteins to affect biological processes such as transposon silencing through epigenetic effects. Recent studies have found that piRNAs are widely dysregulated in tumors and associated with tumor progression and a poor prognosis. Therefore, this study aimed to investigate the effect of piR-1919609 on the proliferation, apoptosis, and drug resistance of ovarian cancer cells. METHODS: In this study, we used small RNA sequencing to screen and identify differentially expressed piRNAs in primary ovarian cancer, recurrent ovarian cancer, and normal ovaries. A large-scale verification study was performed to verify the expression of piR-1919609 in different types of ovarian tissue, including ovarian cancer tissue and normal ovaries, by RT-PCR and to analyze its association with the clinical prognosis of ovarian cancer. The expression of PIWILs in ovarian cancer was verified by RT-PCR, Western blotting and immunofluorescence. The effects of piR-1919609 on ovarian cancer cell proliferation, apoptosis and drug resistance were studied through in vitro and in vivo models. RESULTS: (1) piR-1919609 was highly expressed in platinum-resistant ovarian cancer tissues (p < 0.05), and this upregulation was significantly associated with a poor prognosis and a shorter recurrence time in ovarian cancer patients (p < 0.05). (2) PIWIL2 was strongly expressed in ovarian cancer tissues (p < 0.05). It was expressed both in the cytoplasm and nucleus of ovarian cancer cells. (3) Overexpression of piR-1919609 promoted ovarian cancer cell proliferation, inhibited apoptosis, and promoted tumor growth in nude mice. (4) Inhibition of piR-1919609 effectively reversed ovarian cancer drug resistance. CONCLUSION: In summary, we showed that piR-1919609 is involved in the regulation of drug resistance in ovarian cancer cells and might be an ideal potential target for reversing platinum resistance in ovarian cancer.

Impact of whole grain highland hull-less barley on the denaturing gradient gel electrophoresis profiles of gut microbial communities in rats fed high-fat diets.

Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) is a traditional non-culture technique that can provide a fingerprint of the microbial community. In the field of gut microbiota analysis, PCR-DGGE still holds potential for development. In the present study, we utilized an improved nested PCR-DGGE approach targeting the V3 region of 16S ribosomal DNA to investigate the impact of whole grain highland hull-less barley (WHLB), a cereal known for its significant hypocholesterolemic effect, on the gut microbiota profiles of high-fat diet rats. Seventy-two male Sprague-Dawley rats were divided into four groups and fed a normal control diet, a high-fat diet, or a high-fat diet supplemented with a low or high dose of WHLB for 4 or 8 weeks. The results revealed that the dominant bands varied among different dose groups and further changed with different treatment times. The compositions of bacterial communities in feces and cecal content were similar, but the dominant bacterial bands differed. After performing double DGGE, extracting the bands, sequencing the DNA, and aligning the sequences, a total of 19 bands were classified under the Firmicutes and Bacteroidetes phyla, while two bands were identified as unclassified uncultured bacteria. The relative abundance of Lactobacillus gasseri, Uncultured Prevotella sp., and Clostridium sp. increased following the administration of WHLB. Illumina-based sequencing was employed to assess the reliability of DGGE, demonstrating its reliability in analyzing the dominant taxonomic composition, although it may have limitations in accurately detecting the alpha diversity of bacterial species. IMPORTANCE: While next-generation sequencing has overshadowed polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE), the latter still holds promise for advancing gut microbiota analysis due to its unique advantages. In this study, we used optimized nested PCR-DGGE to investigate the gut microbiota profile of high-fat diet rats after administering whole grain highland hull-less barley. High-throughput sequencing was employed to validate the DGGE results. Our results proved the reliability of PCR-DGGE for analyzing the dominant taxonomic composition while also providing visual evidence of a notable relationship between the composition of cecal and fecal microbial communities, highlighting substantial differences in both richness and abundance.

Semaglutide attenuates doxorubicin-induced cardiotoxicity by ameliorating BNIP3-Mediated mitochondrial dysfunction.

AIMS: Doxorubicin is a powerful chemotherapeutic agent for cancer, whose use is limited due to its potential cardiotoxicity. Semaglutide (SEMA), a novel analog of glucagon-like peptide-1 (GLP-1), has received widespread attention for the treatment of diabetes. However, increasing evidence has highlighted its potential therapeutic benefits on cardiac function. Therefore, the objective of this study was to examine the efficacy of semaglutide in ameliorating doxorubicin-induced cardiotoxicity. METHODS AND RESULTS: Doxorubicin-induced cardiotoxicity is an established model to study cardiac function. Cardiac function was studied by transthoracic echocardiography and invasive hemodynamic monitoring. The results showed that semaglutide significantly ameliorated doxorubicin-induced cardiac dysfunction. RNA sequencing suggested that Bnip3 is the candidate gene that impaired the protective effect of semaglutide in doxorubicin-induced cardiotoxicity. To determine the role of BNIP3 on the effect of semaglutide in doxorubicin-induced cardiotoxicity, BNIP3 with adeno-associated virus serotype 9 (AAV9) expressing cardiac troponin T (cTnT) promoter was injected into tail vein of C57/BL6J mice to overexpress BNIP3, specifically in the heart. Overexpression of BNIP3 prevented the improvement in cardiac function caused by semaglutide. In vitro experiments showed that semaglutide, via PI3K/AKT pathway, reduced BNIP3 expression in the mitochondria, improving mitochondrial function. CONCLUSION: Semaglutide ameliorates doxorubicin-induced mitochondrial and cardiac dysfunction via PI3K/AKT pathway, by reducing BNIP3 expression in mitochondria. The improvement in mitochondrial function reduces doxorubicin-mediated cardiac injury and improves cardiac function. Therefore, semaglutide is a potential therapy to reduce doxorubicin-induced acute cardiotoxicity.