Comparative analysis of the PAL gene family in nine citruses provides new insights into the stress resistance mechanism of Citrus species.

BACKGROUND: The phenylalanine ammonia-lyase (PAL) gene, a well-studied plant defense gene, is crucial for growth, development, and stress resistance. The PAL gene family has been studied in many plants. Citrus is among the most vital cash crops worldwide. However, the PAL gene family has not been comprehensively studied in most Citrus species, and the biological functions and specific underlying mechanisms are unclear. RESULTS: We identified 41 PAL genes from nine Citrus species and revealed different patterns of evolution among the PAL genes in different Citrus species. Gene duplication was found to be a vital mechanism for the expansion of the PAL gene family in citrus. In addition, there was a strong correlation between the ability of PAL genes to respond to stress and their evolutionary duration in citrus. PAL genes with shorter evolutionary times were involved in more multiple stress responses, and these PAL genes with broad-spectrum resistance were all single-copy genes. By further integrating the lignin and flavonoid synthesis pathways in citrus, we observed that PAL genes contribute to the synthesis of lignin and flavonoids, which enhance the physical defense and ROS scavenging ability of citrus plants, thereby helping them withstand stress. CONCLUSIONS: This study provides a comprehensive framework of the PAL gene family in citrus, and we propose a hypothetical model for the stress resistance mechanism in citrus. This study provides a foundation for further investigations into the biological functions of PAL genes in the growth, development, and response to various stresses in citrus.

GLP-1 Receptor Agonists and Risk of Paralytic Ileus: A drug-target Mendelian Randomization Study.

Background: Paralytic ileus (PI), a condition characterized by reduced bowel motor activity without physical obstruction, can be affected by complications from type 2 diabetes (T2D) and anti-diabetic medications. It is unclear of the causal associations of glucagon-like peptide-1 receptor agonists (GLP-1RAs) with the risk of PI in the context of T2D management. Methods: To investigate the causal relationship of GLP-1RAs with PI, we conducted a 2-sample mendelian randomization (MR) study based on summary statistics from genome-wide association studies (GWAS). Genetic variants in the GLP1R were identified as genetical proxies of GLP-1RAs by the glycemic control therapy, based on genetic associations with glycated hemoglobin (GWAS n=344,182) and T2D (n cases/controls =228,499/1,178,783). The effects of GLP-1RAs were estimated for PI risk (n cases/controls =517/182,423) using GWAS data from the FinnGen project. Results: Based on MR analysis, GLP-1RAs are causally associated with a decreased risk of PI (OR per 1 mmol/mol decrease in glycated hemoglobin: 0.21; 95% confidence interval [CI]=0.06-0.69). The magnitude of these benefit exceeded those expected from improved glycemic control more generally. Conclusions: Our study's findings show that GLP-1RAs are causally associated with a lower risk for PI, which provides information to guide clinicians in the selection of appropriate therapies for individuals with T2D while mitigating the risk of developing PI. Investigating the underlying mechanisms that contribute to the lower PI risk associated with GLP-1RAs is essential for a deeper understanding of these associations.

Associations of semaglutide with first-time diagnosis of Alzheimer's disease in patients with type 2 diabetes: Target trial emulation using nationwide real-world data in the US.

INTRODUCTION: Emerging preclinical evidence suggests that semaglutide, a glucagon-like peptide receptor agonist (GLP-1RA) for type 2 diabetes mellitus (T2DM) and obesity, protects against neurodegeneration and neuroinflammation. However, real-world evidence for its ability to protect against Alzheimer's disease (AD) is lacking. METHODS: We conducted emulation target trials based on a nationwide database of electronic health records (EHRs) of 116 million US patients. Seven target trials were emulated among 1,094,761 eligible patients with T2DM who had no prior AD diagnosis by comparing semaglutide with seven other antidiabetic medications. First-ever diagnosis of AD occurred within a 3-year follow-up period and was examined using Cox proportional hazards and Kaplan-Meier survival analyses. RESULTS: Semaglutide was associated with significantly reduced risk for first-time AD diagnosis, most strongly compared with insulin (hazard ratio [HR], 0.33 [95% CI: 0.21 to 0.51]) and most weakly compared with other GLP-1RAs (HR, 0.59 [95% CI: 0.37 to 0.95]). Similar results were seen across obesity status, gender, and age groups. DISCUSSION: These findings support further studies to assess semaglutide's potential in preventing AD. HIGHLIGHTS: Semaglutide was associated with 40% to 70% reduced risks of first-time AD diagnosis in T2DM patients compared to other antidiabetic medications, including other GLP-1RAs. Semaglutide was associated with significantly lower AD-related medication prescriptions. Similar reductions were seen across obesity status, gender, and age groups. Our findings provide real-world evidence supporting the potential clinical benefits of semaglutide in mitigating AD initiation and development in patients with T2DM. These findings support further clinical trials to assess semaglutide's potential in delaying or preventing AD.

Gel-Based Suspension Medium Used in 3D Bioprinting for Constructing Tissue/Organ Analogs.

Constructing tissue/organ analogs with natural structures and cell types in vitro offers a valuable strategy for the in situ repair of damaged tissues/organs. Three-dimensional (3D) bioprinting is a flexible method for fabricating these analogs. However, extrusion-based 3D bioprinting faces the challenge of balancing the use of soft bioinks with the need for high-fidelity geometric shapes. To address these challenges, recent advancements have introduced various suspension mediums based on gelatin, agarose, and gellan gum microgels. The emergence of these gel-based suspension mediums has significantly advanced the fabrication of tissue/organ constructs using 3D bioprinting. They effectively stabilize and support soft bioinks, enabling the formation of complex spatial geometries. Moreover, they provide a stable, cell-friendly environment that maximizes cell viability during the printing process. This minireview will summarize the properties, preparation methods, and potential applications of gel-based suspension mediums in constructing tissue/organ analogs, while also addressing current challenges and providing an outlook on the future of 3D bioprinting.

Characterizing GLP-1 Receptor Agonist Use in Preadolescent and Adolescent Populations.

This cross-sectional study examines the characteristics of preadolescent and adolescent populations who received glucagon-like peptide-1 (GLP-1) receptor agonists.

SARS-CoV-2 Infection and New-Onset Type 2 Diabetes Among Pediatric Patients, 2020 to 2022.

Importance: In adults, diagnoses of new-onset type 2 diabetes (T2D) have increased following diagnosis with COVID-19, but whether this occurs in children is unclear. Objective: To determine whether risk of incident T2D diagnosis is increased during the 6 months after SARS-CoV-2 infection among children. Design, Setting, and Participants: This retrospective cohort study used electronic health records from the TriNetX analytics platforms between January 1, 2020, and December 31, 2022. Pediatric patients aged 10 to 19 years without preexisting diabetes were eligible for inclusion. Data were analyzed from August 15 to September 15, 2023, with supplemental analyses January 20 and August 8 to 13, 2024. Exposures: Diagnosis of COVID-19 or a non-COVID-19 respiratory infection. Main Outcomes and Measures: New diagnosis of T2D compared by risk ratios (RRs) and 95% CIs at 1, 3, and 6 months after index infection. Results: The main study population included 613 602 patients, consisting of 306 801 with COVID-19 (mean [SD] age at index, 14.9 [2.9] years; 52.8% female) and 306 801 with other respiratory infections (ORIs) but no documented COVID-19 (mean [SD] age at index, 14.9 [2.9] years; 52.6% female) after propensity score matching. Risk of a new diagnosis of T2D was significantly increased from day of infection to 1, 3, and 6 months after COVID-19 diagnosis compared with the matched cohort with ORIs (RR at 1 month, 1.55 [95% CI, 1.28-1.89]; RR at 3 months: 1.48 [95% CI, 1.24-1.76]; RR at 6 months: 1.58 [95% CI, 1.35-1.85]). Similar results were found in the subpopulation classified as having overweight or obesity (RR at 1 month: 2.07 [95% CI, 1.12-3.83]; RR at 3 months: 2.00 [95% CI, 1.15-3.47]; RR at 6 months: 2.27 [95% CI, 1.38-3.75]) and the hospitalized subpopulation (RR at 1 month: 3.10 [95% CI, 2.04-4.71]; RR at 3 months: 2.74 [95% CI, 1.90-3.96]; RR at 6 months: 2.62 [95% CI, 1.87-3.66]). Similar elevation in risk was found at 3 and 6 months when excluding patients diagnosed during the interval from the index date to 1 month after infection. Conclusions and Relevance: In this retrospective cohort study of children and adolescents aged 10 to 19 years, the risk of an incident diagnosis of T2D was greater following a COVID-19 diagnosis than in children diagnosed with ORIs. Further study is required to determine whether diabetes persists or reverses later in life.

Antibiotics and Pesticides Enhancing the Transfer of Resistomes among Soil-Bayberry-Fruit Fly Food Chain in the Orchard Ecosystem.

While substantial amounts of antibiotics and pesticides are applied to maintain orchard yields, their influence on the dissemination and risk of antibiotic resisitome in the orchard food chain remains poorly understood. In this study, we characterized the bacterial and fungal communities and differentiated both antibiotic resistance genes (ARGs) and virulence factor genes (VFGs) in the soil, Chinese bayberry (matured and fallen), and fruit fly gut, collected from five geographic locations. Our results showed that fruit fly guts and soils exhibit a higher abundance of ARGs and VFGs compared with bayberry fruits. We identified 112 shared ARGs and 75 shared VFGs, with aminoglycoside and adherence factor genes being among the most abundant. The co-occurrence network revealed some shared microbes, such as Bacillus and Candida, as potential hosts of ARGs, highlighting the vector risks for both above- and below-ground parts of the orchard food chain. Notably, the elevated levels of antibiotics and pesticide residues in orchard soils increase ARGs, mobile genetic elements (MGEs), and VFGs in the soil-bayberry-fruit fly food chain. Our study highlighted that agricultural management, including the overuse of antibiotics and pesticides, could be the key factor in accumulating resistomes in the orchard food chain.

Multimodal ultrasound imaging of a rat model with ischemic heart failure and its relationship to histopathology.

OBJECTIVE: To investigate the value of multimodal ultrasound imaging in assessing ischemic heart failure, and to analyze the relationship between ultrasound parameters and histopathology. METHODS: Thirty male healthy SD rats were randomly divided into a control (n = 10) and a model group (n = 20). The rat model of ischemic heart failure (IHF) was established by the ligation of left anterior descending artery for 4 weeks. Left ventricular ejection fraction (LVEF) and left ventricular cardiac output (LVCO) were determined with routine echocardiography. Global longitudinal strain (GLS) and global circumferential strain (GCS) were determined with Speckle Tracking. Myocardial oxygen saturation (sO2) was measured with photoacoustic (PA) imaging. Hematoxylin and eosin (H&E) staining, transmission electron microscopy, and Masson staining were performed to determine mitochondrial damage and myocardial fibrosis. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the serum levels of cardiac troponin I (cTNT) and N-terminal B-type natriuretic peptide (NT-pro BNP). Pearson correlation analysis was employed to analyze the correlation among LVEF, LVCO, GLS, GCS, sO2, mitochondrial impairment, fibrosis, cTNT and NT-pro BNP. RESULTS: Echocardiography revealed significant systolic function changes in the model group as compared to the control group, characterized by decreased LVEF and CO. The serum levels of cTn-T and NT-proBNP were increased, suggesting myocardial injury and functional impairment. GLS and GCS in the model group was reduced as compared to the control group. Concurrently, a marked reduction in sO2 was observed in the anterior wall of the model rats, whereas that in the posterior wall showed no significant change. Histopathologic examinations unveiled pronounced cellular and subcellular damage, such as disorganization of myocardial fibers and mitochondrial impairment, with the model group presenting a higher Flameng score. Masson's trichrome staining revealed increased myocardial fibrosis. Correlation analyses pinpointed significant associations between echocardiographic parameters, degree of mitochondrial damage, fibrosis, and the levels of cTn-T and NT-proBNP in the model group. This indicated the interrelated nature of structural changes and functional impairment in IHF. Notably, GLS showed the strongest correlations with indicators of myocardial injury. However, anterior wall sO2 did not demonstrate a significant correlation with either histopathologic damage or serum biomarker levels. CONCLUSIONS: Myocardial GLS is a sensitive indicator of pathological myocardial remodeling in heart failure. The multimodal ultrasound can be applied to assess pathologic remodeling in IHF rats.

Late-onset renal TMA and tubular injury in cobalamin C disease: a report of three cases and literature review.

BACKGROUND: Mutation of MMACHC gene causes cobalamin C disease (cblC), an inherited metabolic disorder, which presents as combined methylmalonic aciduria (MMA-uria) and hyperhomocysteinaemia in clinical. Renal complications may also be present in patients with this inborn deficiency. The most common histological change is thrombotic microangiopathy (TMA). However, to our acknowledge, renal tubular injury in the late-onset presentation of cblC is rarely been reported. This study provides a detailed description of the characteristics of kidney disease in cblC deficiency, aiming to improve the early recognition of this treatable disease for clinical nephrologists. CASE PRESENTATION: Here we described three teenage patients who presented with hematuria, proteinuria, and hypertension in clinical presentation. They were diagnosed with renal involvement due to cblC deficiency after laboratory tests revealing elevated serum and urine homocysteine, renal biopsy showing TMA and tubular injury, along with genetic testing showing heterogeneous compound mutations in MMACHC. Hydroxocobalamin, betaine, and L-carnitine were administered to these patients. All of them got improved, with decreased homocysteine, controlled blood pressure, and kidney outcomes recovered. CONCLUSIONS: The clinical diagnosis of cblC disease associated with kidney injury should be considered in patients with unclear TMA accompanied by a high concentration of serum homocysteine, even in teenagers or adults. Early diagnosis and timely intervention are vital to improving the prognosis of cobalamin C disease. CLINICAL TRIAL NUMBER: Not applicable.

Multi-parametric thrombus profiling microfluidics detects intensified biomechanical thrombogenesis associated with hypertension and aging.

Arterial thrombosis is a leading cause of death and disability worldwide with no effective bioassay for clinical prediction. As a symbolic feature of arterial thrombosis, severe stenosis in the blood vessel creates a high-shear, high-gradient flow environment that facilitates platelet aggregation towards vessel occlusion. Here, we present a thrombus profiling assay that monitors the multi-dimensional attributes of thrombi forming in such biomechanical conditions. Using this assay, we demonstrate that different receptor-ligand interactions contribute distinctively to the composition and activation status of the thrombus. Our investigation into hypertensive and older individuals reveals intensified biomechanical thrombogenesis and multi-dimensional thrombus profile abnormalities, endorsing the diagnostic potential of the assay. Furthermore, we identify the hyperactivity of GPIbα-integrin αIIbß3 mechanosensing axis as a molecular mechanism that contributes to hypertension-associated arterial thrombosis. By studying drug-disease interactions and inter-individual variability, our work reveals a need for personalized anti-thrombotic drug selection that accommodates each patient's pathological profile.

Efficacy study of platelet-rich plasma combined with core decompression and bone grafting in the treatment of early-stage avascular necrosis of the femoral head: a retrospective study.

OBJECTIVE: This study aimed to evaluate the effectiveness of combined core decompression (CD), bone grafting (BG), and platelet-rich plasma (PRP) in treating early-stage avascular necrosis of the femoral head (ANFH). METHODS: A retrospective study was conducted on 74 patients (85 hips) with Ficat-Arlet stage I-II ANFH who were treated at our hospital between May 2015 and May 2018. The control group (20 patients, 22 hips) received symptomatic treatments, including weight-bearing reduction and oral analgesics. The CD + BG group (29 patients, 34 hips) underwent CD and ß-tricalcium phosphate bone grafting. The PRP combination group (25 patients, 29 hips) received PRP injections in addition to CD and BG. Patients were followed up for five years to assess the necessity for total hip arthroplasty (THA). Data analysis was performed on those from the CD + BG and PRP groups who did not require THA. Clinical outcomes were evaluated using the Visual Analog Scale (VAS), Harris Hip Score (HHS), and the proportion of patients not accepting THA. RESULTS: At the five-year follow-up, the rate of THA in the control group was 68.18% (15/22), while in the CD + BG group and the PRP combination group, the rates were 17.65% (6/34) and 10.34% (3/29), respectively. There was no statistically significant difference between the CD + BG group and the PRP combination group (P = 0.441), but both differed significantly from the control group (P < 0.001). Kaplan-Meier survival analysis showed that over time, the proportion of patients in the PRP combination group who did not require THA was consistently higher than that in the CD + BG group. Among patients who did not undergo THA, the proportion of Ficat-Arlet stage I-II patients in the PRP combination group was 88.46% (23/26), which was higher than the 64.29% (18/28) in the CD + BG group, showing a significant difference (P = 0.038). VAS score and HHS were compared between the two groups at 6 months, 12 months, and the last follow-up point, with patients in the PRP combination group showing better scores than those in the CD + BG group (p < 0.05) in both metrics. CONCLUSION: The combination therapy of CD, BG, and PRP demonstrates significant advantages in improving symptoms and delaying disease progression in early-stage ANFH.

GLP-1 receptor agonists and pancreatic cancer risk: target trial emulation using real-world data.

BACKGROUND: Data on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on pancreatic cancer incidence are limited and inconsistent. Here we evaluate the association of GLP-1RAs, alone and in combinations, with incident pancreatic cancer risk in a real-world population, stratified by obesity and smoking status. METHODS: This retrospective cohort included patients with T2DM who were prescribed GLP-1RAs or other non-GLP-1RA anti-diabetes medications between January 2013 and March 2019 and had no prior diagnosis of pancreatic cancer. The incident (first-time) diagnosis of pancreatic cancer during a 5-year follow-up was compared between propensity-score matched cohorts of patients prescribed GLP-1RAs vs other non-GLP-1RA anti-diabetes medications. Subgroup analyses were performed in patients stratified by the status of obesity and tobacco use disorder. We also compared GLP-1RA combination therapies with monotherapies. Time-to-first-event analysis was performed using Cox proportional hazards and Kaplan-Meier survival analysis, with the hazard ratio (HR) and 95% confidence interval (CI) calculated. RESULTS: The study population comprised 1,636,056 eligible patients including 167,091 prescribed GLP-1RAs and 1,468,965 prescribed other anti-diabetes medications. GLP-1RAs were associated with a significantly decreased risk for pancreatic cancer incidence compared with each of six non-GLP-1RA anti-diabetes medications with HR ranging from 0.42 to 0.82. The reduction was greater in patients with obesity and tobacco use disorder than in those without. GLP-1RA combination therapies were associated with lower pancreatic cancer risk compared with monotherapies. CONCLUSIONS: GLP-1RAs were associated with reduced pancreatic cancer incidence in patients with T2DM. Further studies and trials are needed to explore mechanisms and confirm causal effects.

Capacity recovery by transient voltage pulse in silicon-anode batteries.

In the quest for high-capacity battery electrodes, addressing capacity loss attributed to isolated active materials remains a challenge. We developed an approach to substantially recover the isolated active materials in silicon electrodes and used a voltage pulse to reconnect the isolated lithium-silicon (LixSi) particles back to the conductive network. Using a 5-second pulse, we achieved >30% of capacity recovery in both Li-Si and Si-lithium iron phosphate (Si-LFP) batteries. The recovered capacity sustains and replicates through multiple pulses, providing a constant capacity advantage. We validated the recovery mechanism as the movement of the neutral isolated LixSi particles under a localized nonuniform electric field, a phenomenon known as dielectrophoresis.

Fatal invasive Aspergillus infection in an elderly patient with hepatitis E: A case report and literature review.

RATIONALE: Elderly patients with acute liver failure are highly susceptible to severe complications, such as invasive fungal infections, due to weakened immune systems and altered gut microbiota. A thorough understanding of liver failure and opportunistic infections is crucial for effective management. PATIENT CONCERNS: An 84-year-old male with acute liver failure from hepatitis E experienced worsening jaundice despite standard treatments. He also developed respiratory symptoms, including blood-streaked sputum, raising concerns about a potential fungal infection. DIAGNOSES: The patient was diagnosed with acute liver failure secondary to hepatitis E and an invasive fungal infection caused by Aspergillus fumigatus. Initial treatments included artificial liver plasma exchange and antifungal prophylaxis. Further diagnostics, including bronchoscopy and next-generation sequencing of alveolar lavage fluid, confirmed the Aspergillus infection. LESSONS: Elderly liver failure patients are particularly prone to opportunistic infections, underscoring the need for vigilant monitoring and early intervention. Despite aggressive treatments, including antifungal therapy and artificial liver support, prognosis remains poor, highlighting the importance of prompt diagnosis and comprehensive management to enhance patient outcomes.

Integrating spatial transcriptomics and single-nucleus RNA-seq revealed the specific inhibitory effects of TGF-ß on intramuscular fat deposition.

Intramuscular fat (IMF) is a complex adipose tissue within skeletal muscle, appearing specially tissue heterogeneous, and the factors influencing its formation remain unclear. In conditions such as diabetes, aging, and muscle wasting, IMF was deposited in abnormal locations in skeletal muscle, damaged the normal physiological functions of skeletal muscle. Here, we used Longissimus dorsi muscles from pigs with different IMF contents as samples and adopted a method combining spatial transcriptome (ST) and single-nucleus RNA-seq to identify the spatial heterogeneity of IMF. ST revealed that genes involved in TGF-ß signaling pathways were specifically highly enriched in IMF. In lean pigs, IMF autocrine produces more TGF-ß2, while in obese pigs, IMF received more endothelial-derived TGF-ß1. In vitro experiments have proven that porcine endothelial cells in a simulated high-fat environment released more TGF-ß1 than TGF-ß2. Moreover, under obesity mice, the addition of TGF-ß after muscle injury abolished IMF production and slowed muscle repair, whereas TGF-ß inhibition accelerated muscle repair. Our findings demonstrate that the TGF-ß pathway specifically regulates these processes, suggesting it as a potential therapeutic target for managing muscle atrophy in obese patients and enhancing muscle repair while reducing IMF deposition.

Fabrication of 3D Biomimetic Smooth Muscle Using Magnetic Induction and Bioprinting for Tissue Regeneration.

Smooth muscles play a vital role in peristalsis, tissue constriction, and relaxation but lack adequate self-repair capability for addressing extensive muscle defects. Engineering scaffolds have been broadly proposed to repair the muscle tissue. However, efforts to date have shown that those engineered scaffolds focus on cell alignment in 2-dimension (2D) and fail to direct muscle cells to align in 3D area, which is irresolvable to remodel the muscle architecture and restore the muscle functions like contraction and relaxation. Herein, we introduced an iron oxide (Fe3O4) filament-embedded gelatin (Gel)-silk fibroin composite hydrogel in which the oriented Fe3O4 self-assembled and functioned as micro/nanoscale geometric cues to induce cell alignment growth. The hydrogel scaffold can be designed to fabricate aligned or anisotropic muscle by combining embedded 3D bioprinting with magnetic induction to accommodate special architectures of muscular tissues in the body. Particularly, the bioprinted muscle-like matrices effectively promote the self-organization of smooth muscle cells (SMCs) and the directional differentiation of bone marrow mesenchymal stem cells (BMSCs) into SMCs. This biomimetic muscle accelerated tissue regeneration, enhancing intercellular connectivity within the muscular tissue, and the deposition of fibronectin and collagen I. This work provides a novel approach for constructing engineered biomimetic muscles, holding significant promise for clinical treatment of muscle-related diseases in the future.

Ru Single Atom Dispersed Cu Nanoparticle with Dual Sites Enables Outstanding Photocatalytic CO2 Reduction.

Cu-based catalysts are promising candidates for CO2 reduction owing to the favorable energetics of Cu sites for CO2 adsorption and transformation. However, CO2 reduction involving insurmountable activation barriers and various byproducts remains a significant challenge to achieve high activity and selectivity. Herein, a photocatalyst constructed with single-Ru-site-on-Cu-nanoparticle on Bi4Ti3O12 exhibits exceptional activity and selectivity for CO2 conversion to CO. The experimental and theoretical results consistently reveal that the Ru-Cu dual sites allow the rapid transfer of photogenerated carriers for closely interacting with CO2 molecules. Importantly, the Ru-Cu dual sites exhibit extremely strong CO2 adsorption ability, and the Gibbs free energy of the rate-determining step (*CO2 to *COOH) has been significantly reduced, synergistically enhancing the entire CO2 conversion process. The optimal BTOCu2Ru0.5 photocatalyst manifests a high performance for selective reduction of CO2 to CO, yielding 10.84 µmol over 15 mg of photocatalyst in 4 h (180.67 µmol·g-1·h-1) under a 300 W Xe lamp without any photosensitizer and sacrificial reagent, outperforming all bismuth-based materials and being one of the best photocatalysts ever reported under similar reaction conditions. This work presents a strategy for the rational design of multiple metal sites toward efficient photocatalytic reduction of CO2.

Semaglutide and Opioid Overdose Risk in Patients With Type 2 Diabetes and Opioid Use Disorder.

This cohort study uses emulation target trial methods to evaluate whether semaglutide is associated with lower rates of opioid overdose among patients with type 2 diabetes (T2D) and opioid use disorder (OUD).

ZASP: A Highly Compatible and Sensitive ZnCl2 Precipitation-Assisted Sample Preparation Method for Proteomic Analysis.

Universal sample preparation for proteomic analysis that enables unbiased protein manipulation, flexible reagent use, and low protein loss is required to ensure the highest sensitivity of downstream liquid chromatography-mass spectrometry (LC-MS) analysis. To address these needs, we developed a ZnCl2 precipitation-assisted sample preparation method (ZASP) that depletes harsh detergents and impurities in protein solutions prior to trypsin digestion via 10 min of ZnCl2 and methanol-induced protein precipitation at room temperature (RT). ZASP can remove trypsin digestion and LC-MS incompatible detergents such as SDS, Triton X-100, and urea at high concentrations in solution and unbiasedly recover proteins independent of the amount of protein input. We demonstrated the sensitivity and reproducibility of ZASP in an analysis of samples with 1 µg to 1000 µg of proteins. Compared to commonly used sample preparation methods such as SDC-based in-solution digestion, acetone precipitation, FASP, and SP3, ZASP has proven to be an efficient approach. Here, we present ZASP, a practical, robust, and cost-effective proteomic sample preparation method that can be applied to profile different types of samples.