12-Lipoxygenase inhibition suppresses islet immune and inflammatory responses and delays autoimmune diabetes in human gene replacement mice.

Type 1 diabetes (T1D) is characterized by the autoimmune destruction of insulin-producing ß cells and involves an interplay between ß cells and cells of the innate and adaptive immune systems. We investigated the therapeutic potential of targeting 12-lipoxygenase (12-LOX), an enzyme implicated in inflammatory pathways in ß cells and macrophages, using a mouse model in which the endogenous mouse Alox15 gene is replaced by the human ALOX12 gene. Our findings demonstrate that VLX-1005, a potent 12-LOX inhibitor, effectively delays the onset of autoimmune diabetes in human gene replacement non-obese diabetic (NOD) mice. By spatial proteomics analysis, VLX-1005 treatment resulted in marked reductions in infiltrating T and B cells and macrophages with accompanying increases in immune checkpoint molecules PD-L1 and PD-1, suggesting a shift towards an immune-suppressive microenvironment. RNA sequencing analysis of isolated islets from inhibitor-treated mice revealed significant alteration of cytokine-responsive pathways. RNA sequencing of polarized proinflammatory macrophages showed that VLX-1005 significantly reduced the interferon response. Our studies demonstrate that the ALOX12 human replacement gene mouse provides a platform for the preclinical evaluation of LOX inhibitors and supports VLX-1005 as an inhibitor of human 12-LOX that engages the enzymatic target and alters the inflammatory phenotypes of islets and macrophages to promote the delay of autoimmune diabetes.

StreamSAXS: a Python-based workflow platform for processing streaming SAXS/WAXS data.

StreamSAXS is a Python-based small- and wide-angle X-ray scattering (SAXS/WAXS) data analysis workflow platform with graphical user interface (GUI). It aims to provide an interactive and user-friendly tool for analysis of both batch data files and real-time data streams. Users can easily create customizable workflows through the GUI to meet their specific needs. One characteristic of StreamSAXS is its plug-in framework, which enables developers to extend the built-in workflow tasks. Another feature is the support for both already acquired and real-time data sources, allowing StreamSAXS to function as an offline analysis platform or be integrated into large-scale acquisition systems for end-to-end data management. This paper presents the core design of StreamSAXS and provides user cases demonstrating its utilization for SAXS/WAXS data analysis in offline and online scenarios.

Proximity-Dependent Activation of Split DNAzyme Kinase.

Binary (also known as split) nucleic acid enzymes have emerged as novel tools in biosensors. We report a new split strategy to split the DNAzyme kinase into two independent and non-functional fragments, denoted DK1sub and DK1enz. In the presence of the specific target, their free ends are brought sufficiently close to interact with each other without the formation of Watson-Crick base pairings between Dk1sub and Dk1enz, thus allowing the DNA phosphorylation reaction. We term this approach proximity-dependent activation of split DNAzyme kinase (ProxSDK). The utility of ProxSDK is demonstrated by engineering a biosensing system that is capable of measuring specific DNA-protein interactions. We envision that the approach described herein will find useful applications in biosensing, imaging, and clinical diagnosis.

Atopic Dermatitis and Psoriasis: Similarities and Differences in Metabolism and Microbiome.

Atopic dermatitis and psoriasis are common chronic inflammatory diseases of high incidence that share some clinical features, including symptoms of pruritus and pain, scaly lesions, and histologically, acanthosis and hyperkeratosis. Meanwhile, they are both commonly comorbid with metabolic disorders such as obesity and diabetes, indicating that both diseases may exist with significant metabolic disturbances. Metabolomics reveals that both atopic dermatitis and psoriasis have abnormalities in a variety of metabolites, including lipids, amino acids, and glucose. Meanwhile, recent studies have highlighted the importance of the microbiome and its metabolites in the pathogenesis of atopic dermatitis and psoriasis. Metabolic alterations and microbiome dysbiosis can also affect the immune, inflammatory, and epidermal barrier, thereby influencing the development of atopic dermatitis and psoriasis. Focusing on the metabolic and microbiome levels, this review is devoted to elaborating the similarities and differences between atopic dermatitis and psoriasis, thus providing insights into the intricate relationship between both conditions.

Enhanced electroactive bacteria enrichment and facilitated extracellular electron transfer in microbial fuel cells via polydopamine coated graphene aerogel anode.

The structure and surface physicochemical properties of anode play a crucial role in microbial fuel cells (MFCs). To enhance the enrichment of exoelectrogen and facilitate extracellular electron transfer (EET), a three-dimensional macroporous graphene aerogel with polydopamine coating was successfully introduced to modify carbon brush (PGA/CB). The three-dimensional graphene aerogel (GA) with micrometer pores improved the space utilization efficiency of microorganisms. Polydopamine (PDA) coating enhanced the physicochemical properties of the electrode surface by introducing abundant functional groups and nitrogen-containing active sites. MFCs equipped with PGA/CB anodes (PGA/CB-MFCs) demonstrated superior power generation compared to GA/CB-MFCs and CB-MFCs (MFCs with GA/CB and CB anodes respectively), including a 23.0 % and 30.1 % reduction in start-up time, and an increase in maximum power density by 2.43 and 1.24 times respectively. The higher bioelectrochemical activity exhibited by the biofilm of PGA/CB anode and the promoted riboflavin secretion by PGA modification imply the enhanced EET efficiency. 16S rRNA high-throughput sequence analysis of the biofilms revealed successful enrichment of Geobacter on PGA/CB anodes. These findings not only validate the positive impact of the synergistic effects between GA and PDA in promoting EET and improving MFC performance but also provide valuable insights for electrode design in other bioelectrochemical systems.

The regulatory role of m6A modification in the maintenance and differentiation of embryonic stem cells.

As the most prevalent and reversible internal epigenetic modification in eukaryotic mRNAs, N 6-methyladenosine (m6A) post-transcriptionally regulates the processing and metabolism of mRNAs involved in diverse biological processes. m6A modification is regulated by m6A writers, erasers, and readers. Emerging evidence suggests that m6A modification plays essential roles in modulating the cell-fate transition of embryonic stem cells. Mechanistic investigation of embryonic stem cell maintenance and differentiation is critical for understanding early embryonic development, which is also the premise for the application of embryonic stem cells in regenerative medicine. This review highlights the current knowledge of m6A modification and its essential regulatory contribution to the cell fate transition of mouse and human embryonic stem cells.

Personalized surgical recommendations and quantitative therapeutic insights for patients with metastatic breast cancer: Insights from deep learning.

Background: The role of surgery in metastatic breast cancer (MBC) is currently controversial. Several novel statistical and deep learning (DL) methods promise to infer the suitability of surgery at the individual level. Objective: The objective of this study was to identify the most applicable DL model for determining patients with MBC who could benefit from surgery and the type of surgery required. Methods: We introduced the deep survival regression with mixture effects (DSME), a semi-parametric DL model integrating three causal inference methods. Six models were trained to make individualized treatment recommendations. Patients who received treatments in line with the DL models' recommendations were compared with those who underwent treatments divergent from the recommendations. Inverse probability weighting (IPW) was used to minimize bias. The effects of various features on surgery selection were visualized and quantified using multivariate linear regression and causal inference. Results: In total, 5269 female patients with MBC were included. DSME was an independent protective factor, outperforming other models in recommending surgery (IPW-adjusted hazard ratio [HR] = 0.39, 95% confidence interval [CI]: 0.19-0.78) and type of surgery (IPW-adjusted HR = 0.66, 95% CI: 0.48-0.93). DSME was superior to other models and traditional guidelines, suggesting a higher proportion of patients benefiting from surgery, especially breast-conserving surgery. The debiased effect of patient characteristics, including age, tumor size, metastatic sites, lymph node status, and breast cancer subtypes, on surgery decision was also quantified. Conclusions: Our findings suggested that DSME could effectively identify patients with MBC likely to benefit from surgery and the specific type of surgery needed. This method can facilitate the development of efficient, reliable treatment recommendation systems and provide quantifiable evidence for decision-making.

Modulating porous silicon-carbon anode stability: Carbon/silicon carbide semipermeable layer mitigates silicon-fluorine reaction and enhances lithium-ion transport.

Silicon-based material is regarded as one of the most promising anodes for next-generation high-performance lithium-ion batteries (LIBs) due to its high theoretical capacity and low cost. Harnessing silicon carbide's robustness, we designed a novel porous silicon with a sandwich structure of carbon/silicon carbide/Ag-modified porous silicon (Ag-PSi@SiC@C). Different from the conventional SiC interface characterized by a frail connection, a robust dual covalent bond configuration, dependent on SiC and SiOC, has been successfully established. Moreover, the innovative sandwich structure effectively reduces detrimental side reactions on the surface, eases volume expansion, and bolsters the structural integrity of the silicon anode. The incorporation of silver nanoparticles contributes to an improvement in overall electron transport capacity and enhances the kinetics of the overall reaction. Consequently, the Ag-PSi@SiC@C electrode, benefiting from the aforementioned advantages, demonstrates a notably elevated lithium-ion mobility (2.4 * 10-9 cm2·s-1), surpassing that of silicon (5.1 * 10-12 cm2·s-1). The half-cell featuring Ag-PSi@SiC@C as the anode demonstrated robust rate cycling stability at 2.0 A/g, maintaining a capacity of 1321.7 mAh/g, and after 200 cycles, it retained 962.6 mAh/g. Additionally, the full-cell, featuring an Ag-PSi@SiC@C anode and a LiFePO4 (LFP) cathode, exhibits outstanding longevity. Hence, the proposed approach has the potential to unearth novel avenues for the extended exploration of high-performance silicon-carbon anodes for LIBs.

A new strategy for the treatment of Parkinson's disease: Discovery and bio-evaluation of the first central-targeting tyrosinase inhibitor.

The high level of tyrosinase leads to the generation of neuromelanin, further causing the abnormality of redox-related protein level and mediating the occurrence and development of Parkinson's disease (PD). However, the existing tyrosinase inhibitors are mostly natural product extracts or polyphenolic derivatives, which hindered them from penetrating the blood-brain barrier (BBB). Herein, we obtained a novel tyrosinase inhibitor, 2-06 (tyrosinase: monophenolase IC50 = 70.44 ± 22.69 µM, diphenolase IC50 = 1.89 ± 0.64 µM), through the structure-based screening method. The compound 2-06 presented good in vitro and in vivo safety, and can inhibit the tyrosinase and melanogenesis in B16F10. Moreover, this compound showed neuroprotective effects and Parkinsonism behavior improving function. 2-06 was proved to penetrate the BBB and enter the central nervous system (CNS). The exploration of the binding mode between 2-06 and tyrosinase provided the foundation for the subsequent structural optimization. This is the first research to develop a central-targeting tyrosinase inhibitor, which is crucial for in-depth study on the new strategy for utilizing tyrosinase inhibitors to treat PD.

Natural defence mechanisms of electrochemically active biofilms: From the perspective of microbial adaptation, survival strategies and antibiotic resistance.

Electrochemically active biofilms (EABs) play an ever-growingly critical role in the biological treatment of wastewater due to its low carbon footprint and sustainability. However, how the multispecies biofilms adapt, survive and become tolerant under acute and chronic toxicity such as antibiotic stress still remains well un-recognized. Here, the stress responses of EABs to tetracycline concentrations (CTC) and different operation schemes were comprehensively investigated. Results show that EABs can quickly adapt (start-up time is barely affected) to low CTC (≤ 5 µM) exposure while the adaptation time of EABs increases and the bioelectrocatalytic activity decreases at CTC ≥ 10 µM. EABs exhibit a good resilience and high anti-shocking capacity under chronic and acute TC stress, respectively. But chronic effects negatively affect the metabolic activity and extracellular electron transfer, and simultaneously change the spatial morphology and microbial community structure of EABs. Particularly, the typical exoelectrogens Geobacter anodireducens can be selectively enriched under chronic TC stress with relative abundance increasing from 45.11% to 85.96%, showing stronger TC tolerance than methanogens. This may be attributed to the effective survival strategies of EABs in response to TC stress, including antibiotic efflux regulated by tet(C) at the molecular level and the secretion of more extracellular proteins in the macro scale, as the C=O bond in amide I of aromatic amino acids plays a critical role in alleviating the damage of TC to cells. Overall, this study highlights the versatile defences of EABs in terms of microbial adaptation, survival strategies, and antibiotic resistance, and deepens the understanding of microbial communities' evolution of EABs in response to acute and chronic TC stress.

24-Hour Urinary Sodium Excretion Is Associated With Increased Risk of Pancreatic Cancer: A Prospective Cohort Study.

INTRODUCTION: This study builds on previous research and its limitations, which indicate the need for further investigation in prospective cohorts. Our aim was to explore the association between estimated 24-hour urinary sodium excretion (indicative of daily sodium consumption) and the occurrence of pancreatic cancer in the UK Biobank's large prospective cohort. METHODS: Using the INTERSALT equation, the study computed estimated 24-hour urinary sodium excretion by analyzing the baseline spot urine sodium measurements of 434,372 individuals enrolled in the UK Biobank. Pancreatic cancer cases were identified through UK cancer registries. Adjusted Cox proportional hazards models were used to evaluate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between estimated 24-hour urinary sodium excretion and the risk of pancreatic cancer. RESULTS: Over a median follow-up period of 13.8 years, 1,765 cases of pancreatic cancer were detected. The multivariable adjusted Cox model showed that each 1-gram rise in estimated 24-hour urinary sodium excretion corresponded to a 1.12 HR for incident pancreatic cancer (95% CI: 1.03, 1.22). The estimated HR for 24-hour urinary sodium excretion in binary form was 1.23 (95% CI: 1.05, 1.44). Compared with the lowest group, the group with the highest estimated 24-hour urinary sodium excretion exhibited an HR of 1.38 (95% CI: 1.21, 1.58). DISCUSSION: These results propose an association between elevated sodium consumption and a heightened risk of pancreatic cancer. Further validation and exploration of potential mechanisms are warranted.

Pituitary-adrenal axis dysfunction induced by tislelizumab immunotherapy for non-small cell lung cancer: a case series and literature review.

BACKGROUND: Adverse events of secondary adrenal insufficiency caused by anti-PD-1 immune agents are relatively rare in clinical practice, so in this article, we retrospectively analyzed three patients who suffered secondary adrenal cortex dysfunction caused by tislelizumab immunotherapy for Non-Small Cell Lung Cancer (NSCLC)and reviewed the literature. This rare immune-related adverse event was investigated by summarizing the clinical features of the patients. CASE PRESENTATION: We reported three NSCLC patients who suffered secondary adrenal cortex dysfunction induced by tislelizumab immunotherapy at our hospital from July 2021 to October 2023. We analyzed and summarized the clinical characteristic, laboratory examination, pathological staging, etc. We also reviewed related literature of pituitary inflammation and adrenal cortex dysfunction caused by immunotherapy. RESULTS: The median age of the three patients was 56 years. All the patients had a history of smoking. After receiving tislelizumab treatment (median cycle: 7), laboratory examination showed a decrease in morning cortisol and adrenocorticotropic hormone (ACTH), both were diagnosed with secondary adrenal insufficiency. Only one patient had symptoms of fatigue, vomiting, and weight loss. One of these patients also had simultaneous subclinical hypothyroidism. All three patients discontinued immunotherapy and received replacement therapy with glucocorticoids. At the last follow-up, none of the three patients restarted immunotherapy, because cortisol did not return to normal. This is similar to that of previous reports. CONCLUSION: Based on previous reports and our three cases, when laboratory tests of NSCLC patients receiving immunotherapy showed a decrease in morning cortisol and ACTH levels, especially when clinical symptoms were obvious, the possibility of immunotherapy-related pituitary inflammation causing secondary adrenal cortex dysfunction should be considered. Prompt monitoring and hormone replacement therapy should be provided to prevent adrenal crises.

The Association Between Surgery and Mild Cognitive Impairment: Insight from a Case-Control Study.

Background: Surgery may be associated with postoperative cognitive impairment in elder participants, yet the extent of its association with mild cognitive impairment (MCI) remains undetermined. Objective: To determine the relationship between surgery and MCI. Methods: The data of participants from the Alzheimer's Disease Neuroimaging Initiative were analyzed, including individuals with MCI or normal cognition. We focused on surgeries conducted after the age of 45, categorized by the number of surgeries, surgical risk, and the age at which surgeries occurred. Multivariable logistic regression was employed to determine the association between surgery and the development of MCI. Results: The study is comprised of 387 individuals with MCI and 578 cognitively normal individuals. The overall surgery exposure (adjusted OR = 1.14, [95% CI 0.83, 1.56], p = 0.43) and the number of surgeries (adjusted OR = 0.92  [0.62, 1.36], p = 0.67 for single exposure, adjusted OR = 1.12 [0.71, 1.78], p = 0.63 for two exposures, adjusted OR = 1.38 [0.95, 2.01], p = 0.09 for three or more exposures compared to no exposure as the reference) were not associated with the development of MCI. However, high-risk surgeries (adjusted OR = 1.79 [1.00, 3.21], p = 0.049) or surgeries occurring after the age of 75 (adjusted OR = 2.01 [1.03, 3.90], p = 0.041) were associated with a greater risk of developing MCI. Conclusions: High risk surgeries occurring at an older age contribute to the development of MCI, indicating a complex of mechanistic insights for the development of postoperative cognitive impairment.

Molybdenum-Doped Cobalt-Free Cathode Realizing the Electrochemical Stability by Enhanced Covalent Bonding.

The doping strategy effectively enhances the capacity and cycling stability of cobalt-free nickel-rich cathodes. Understanding the intrinsic contributions of dopants is of great importance to optimize the performances of cathodes. This study investigates the correlation between the structure modification and their performances of Mo-doped LiNi0.8Mn0.2O2 (NM82) cathode. The role of doped Mo's valence state has been proved functional in both lattice structural modification and electronic state adjustment. Although the high-valence of Mo at the cathode surface inevitably reduces Ni valence for electronic neutrality and thus causes ion mixing, the original Mo valence will influence its diffusion depth. Structural analyses reveal Mo doping leads to a mixed layer on the surface, where high-valence Mo forms a slender cation mixing layer, enhancing structural stability and Li-ion transport. In addition, it is found that the high-valence dopant of Mo6+ ions partially occupies the unfilled 4d orbitals, which may strengthen the Mo─O bond through increased covalency and therefore reduce the oxygen mobility. This results in an impressive capacity retention (90.0% after 200 cycles) for Mo-NM82 cathodes with a high Mo valence state. These findings underscore the valence effect of doping on layered oxide cathode performance, offering guidance for next-generation cathode development.

Brain to brain musical interaction: A systematic review of neural synchrony in musical activities.

The use of hyperscanning technology has revealed the neural mechanisms underlying multi-person interaction in musical activities. However, there is currently a lack of integration among various research findings. This systematic review aims to provide a comprehensive understanding of the social dynamics and brain synchronization in music activities through the analysis of 32 studies. The findings illustrate a strong correlation between inter-brain synchronization (IBS) and various musical activities, with the frontal, central, parietal, and temporal lobes as the primary regions involved. The application of hyperscanning not only advances theoretical research but also holds practical significance in enhancing the effectiveness of music-based interventions in therapy and education. The review also utilizes Predictive Coding Models (PCM) to provide a new perspective for interpreting neural synchronization in music activities. To address the limitations of current research, future studies could integrate multimodal data, adopt novel technologies, use non-invasive techniques, and explore additional research directions.

Incidence and influencing factors related to social isolation among HIV/AIDS patients: Protocol for a systematic review and meta-analysis.

BACKGROUND: People living with HIV (PLWH) are susceptible to social isolation as a result of stigma and discrimination, which not only diminishes adherence to antiretroviral therapy but also heightens the risks of hospital readmission, depression, and mortality. However, there is currently no systematic review addressing the occurrence and impact of social isolation in individuals with HIV. Therefore, this study undertook a comprehensive systematic review and meta-analysis of existing literature to examine the prevalence and influencing factors associated with social isolation among PLWH. METHODS AND ANALYSIS: PubMed, EMBASE, CINAHL, Cochrane Library, Web of Science, Google Scholar, China Science and Technology Journal Database, The China National Knowledge Infrastructure, WanFang Data and Chinese Biomedicine Literature Database will be searched from the establishment of the database to the latest search date. Literature screening, data extraction and literature quality assessment will be done independently by two researchers and results will be cross-referenced. Data analysis will be performed using stata15.1 software. Risk of publication bias will be assessed using Begg's and Egger's methods. Heterogeneity between studies will then be assessed using the I2 index and its 95% CI and Q statistics. Sources of heterogeneity will be accounted for by subgroup and sensitivity analyses. RESULTS: The results may reveal the prevalence of social isolation among PLWH and provide data support for understanding its etiology and prevention. CONCLUSION: By systematically reviewing the existing literature on social isolation among PLWH, this study aims to provide a comprehensive understanding of the prevalence of social isolation within this population, elucidate the detrimental effects it poses for people affected by HIV, and effectively inform targeted interventions for high-risk groups. Furthermore, these findings offer valuable insights to support evidence-based decision-making in public health policy. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42024499044.

Dapagliflozin attenuates AKI to CKD transition in diabetes by activating SIRT3/PGC1-α signaling and alleviating aberrant metabolic reprogramming.

BACKGROUND: Patients with diabetes are prone to acute kidney injury (AKI) with a high mortality rate, poor prognosis, and a higher risk of progression to chronic kidney disease than non-diabetic patients. METHODS: Streptozotocin (STZ)-treated type 1 and db/db type 2 diabetes model were established, AKI model was induced in mice by ischemia-reperfusion injury(IRI). Mouse proximal tubular cell cells were subjected to high glucose and hypoxia-reoxygenation in vitro. Transcriptional RNA sequencing was performed for clustering analysis and target gene screening. Renal structural damage was determined by histological staining, whereas creatinine and urea nitrogen levels were used to measure renal function. RESULTS: Deteriorated renal function and renal tissue damage were observed in AKI mice with diabetic background. RNA sequencing showed a decrease in fatty acid oxidation (FAO) pathway and an increase in abnormal glycolysis. Treatment with Dapa, Sitagliptin(a DPP-4 inhibitor)and insulin reduced blood glucose levels in mice, and improved renal function. However, Dapa had a superior therapeutic effect and alleviated aberrant FAO and glycosis. Dapa reduced cellular death in cultured cells under high glucose hypoxia-reoxygenation conditions, alleviated FAO dysfunction, and reduced abnormal glycolysis. RNA sequencing showed that SIRT3 expression was reduced in diabetic IRI, which was largely restored by Dapa intervention. 3-TYP, a SIRT3 inhibitor, reversed the renal protective effects of Dapa and mediated abnormal FAO and glycolysis in mice and tubular cells. CONCLUSION: Our study provides experimental evidence for the use of Dapa as a means to reduce diabetic AKI by ameliorating metabolic reprogramming in renal tubular cells.

Thermal Effect Management via Entropy Variation Strategy to Improve the Catalyst Stability in Acetylene Hydrogenation.

The dynamic structure evolution of heterogeneous catalysts during reaction has gained great attention recently. However, controllably manipulating dynamic process and then feeding back catalyst design to extend the lifetime remains challenging. Herein, we proposed an entropy variation strategy to develop a dynamic CuZn-Co/HEOs catalyst, in which the non-active Co nano-islands play a crucial role in controlling thermal effect via timely capturing and utilizing reaction heat generated on the adjacent active CuZn alloys, thus solving the deactivation problem of Cu-based catalysts. Specifically, heat sensitive Co nano-islands experienced an entropy increasing process of slowly redispersion during the reaction. Under such heat dissipation effect, the CuZn-Co/HEOs catalyst exhibited 95.7% ethylene selectivity and amazing long-term stability (>530 h) in the typical exothermic acetylene hydrogenation. Aiming at cultivating it as a catalyst with promising industrial potential, we proposed a simple regeneration approach via an entropy decreasing process.

Medication and procedural abortion uptake during a period of increasing abortion hostility.

Hundreds of state-level abortion restrictions were implemented in the US between 2010 and 2020. Medication abortion was being widely adopted during this same period. Understanding the impact of health policies and political climate will improve the delivery of and access to reproductive healthcare in a period of rapid change. To measure the association between state abortion hostility and mifepristone and procedural abortion rates, we conducted a state-level repeated cross-sectional study using 2010-2020 employer-sponsored insurance claims data from Merative MarketScan. The exposure of interest was a 13-point state-level abortion hostility score based on the presence of policies which either reduce or protect access to abortion. Outcomes of interest were annual mifepristone and procedural abortion claims per 100,000 enrollees. We used a linear mixed model adjusting for urbanicity, age group, and year. We assessed whether temporal trends in abortion claims were modified by state abortion hostility by interacting year with two measurements of abortion hostility: baseline score in 2010 and change from baseline score. We found that median state-level mifepristone claims increased from 20 to 37 per 100,000 included enrollees; meanwhile, median procedural abortions claims decreased from 69 to 20 per 100. For mifepristone, every unit increase in a state's baseline abortion hostility score was associated with 7.5 (CI, -12 to -3.6) fewer mifepristone claims per 100,000 in 2010. For states with baseline hostility and change scores of zero, we did not observe a significant time trend over the 11 year study period. For every unit increase in baseline hostility, the time trend changed by 0.5 fewer claims (CI, -0.8 to -0.2) per 100,000 per year. States with higher baseline abortion hostility had fewer overall abortions, less uptake of mifepristone abortions, and slower decline in procedural abortions between 2010 and 2020. Changes in hostility from new restrictions during this time period did not significantly impact claims. Advocates for abortion access must simultaneously attend to individual abortion policies and the overall political climate. Updated research on the relationship between political climate and the evolving clinical landscape of abortion care is needed to inform this work.

Nano-Se exhibits limited protective effect against heat stress induced poor breast muscle meat quality of broilers compared with other selenium sources.

BACKGROUND: At present, heat stress (HS) has become a key factor that impairs broiler breeding industry, which causes growth restriction and poor meat quality of broilers. Selenium (Se) is an excellent antioxidant and plays a unique role in meat quality improvement. Recent years, nano-selenium (NanoSe) has received tremendous attention in livestock production, due to its characteristic and good antibacterial performance in vitro. Here, we developed the heat stressed-broiler model to investigate the protective effects of NanoSe on growth performance and meat quality of broilers and compare whether there are differences with that of other Se sources (Sodium selenite, SS; Selenoyeast, SeY; Selenomethionine, SeMet). RESULTS: HS jeopardized the growth performance and caused poor meat quality of breast muscle in broilers, which were accompanied by lowered antioxidant capacity, increased glycolysis, increased anaerobic metabolism of pyruvate, mitochondrial stress and abnormal mitochondrial tricarboxylic acid (TCA) cycle. All Se sources supplementation exhibited protective effects, which increased the Se concentration and promoted the expression of selenoproteins, improved the mitochondrial homeostasis and the antioxidant capacity, and promoted the TCA cycle and the aerobic metabolism of pyruvate, thus improved the breast muscle meat quality of broilers exposed to HS. However, unlike the other three Se sources, the protective effect of NanoSe on meat quality of heat stressed-broilers was not ideal, which exhibited limited impact on the pH value, drip loss and cooking loss of the breast muscle. Compared with the other Se sources, broilers received NanoSe showed the lowest levels of slow MyHC, the highest levels of fast MyHC and glycogen, the highest mRNA levels of glycolysis-related genes (PFKM and PKM), the highest protein expression of HSP60 and CLPP, and the lowest enzyme activities of GSH-Px, citroyl synthetase (CS) and isocitrate dehydrogenase (ICD) in breast muscle. Consistent with the SS, the Se deposition in breast muscle of broilers received NanoSe was lower than that of broilers received SeY or SeMet. Besides, the regulatory efficiency of NanoSe on the expression of key selenoproteins (such as SELENOS) in breast muscle of heat stressed-broilers was also worse than that of other Se sources. CONCLUSION: Through comparing the meat quality, Se deposition, muscle fiber type conversion, glycolysis, mitochondrial homeostasis, and mitochondrial TCA cycle-related indicators of breast muscle in heat stressed broilers, we found that the protective effects of organic Se (SeY and SeMet) are better than that of inorganic Se (SS) and NanoSe. As a new Se source, though NanoSe showed some protective effect on breast muscle meat quality of heat stressed broilers, the protective effect of NanoSe is not ideal, compared with other Se sources.