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Background: This study evaluated the efficacy and safety of low‐dose anlotinib combined with immune checkpoint inhibitors as second‐line or later treatment for extensive‐stage small cell lung cancer (ES‐SCLC). Methods: The study included 42 patients with ES‐SCLC who were treated with low‐dose anlotinib combined with programmed cell death protein 1/programmed cell death‐ligand 1 inhibitors at Henan Cancer Hospital between March 2019 and August 2022. We retrospectively analyzed the efficacy and safety data for these patients. Indicators assessed included progression‐free survival (PFS), overall survival (OS), the overall response rate (ORR), the disease control rate (DCR), and adverse events (AEs). Prognostic factors were identified in univariate and multivariate analyses. Results: Median PFS was 11.0 months (95% CI: 7.868–14.132) and median OS was 17.3 months (95% CI: 11.517–23.083). The ORR was 28.5% and the DCR was 95.2%. Treatment‐related AEs were noted in 27 patients (64.3%), the most common of which was thyroid dysfunction (26.2%). Grade 3/4 treatment‐related AEs were observed in two patients (4.8%). Conclusions: A combination of low‐dose anlotinib and immune checkpoint inhibitors as second‐line or later treatment for ES‐SCLC may achieve longer PFS and OS and have manageable AEs. [ABSTRACT FROM AUTHOR]

In recent years, the incidence rate of diabetes mellitus (DM), including type 1 diabetes mellitus(T1DM), type 2 diabetes mellitus(T2DM), and gestational diabetes mellitus (GDM), has increased year by year and has become a major global health problem. DM can lead to serious complications of macrovascular and microvascular. Tryptophan (Trp) is an essential amino acid for the human body. Trp is metabolized in the body through the indole pathway, kynurenine (Kyn) pathway and serotonin (5-HT) pathway, and is regulated by intestinal microorganisms to varying degrees. These three metabolic pathways have extensive regulatory effects on the immune, endocrine, neural, and energy metabolism systems of the body, and are related to the physiological and pathological processes of various diseases. The key enzymes and metabolites in the Trp metabolic pathway are also deeply involved in the pathogenesis of DM, playing an important role in pancreatic function, insulin resistance (IR), intestinal barrier, and angiogenesis. In DM and its complications, there is a disruption of Trp metabolic balance. Several therapy approaches for DM and complications have been proven to modify tryptophan metabolism. The metabolism of Trp is becoming a new area of focus for DM prevention and care. This paper reviews the impact of the three metabolic pathways of Trp on the pathogenesis of DM and the alterations in Trp metabolism in these diseases, expecting to provide entry points for the treatment of DM and its complications. [Display omitted] • Tryptophan catabolism is influenced by intestinal microorganisms. • Recent advances in abnormal tryptophan catabolism in diabetes and complications. • Some tryptophan catabolites can be used as risk markers for diabetes and complications. • Role of tryptophan metabolites in diabetes. • Tryptophan metabolism as a potential target for the treatment of diabetes and complications. [ABSTRACT FROM AUTHOR]

Industrial ammonia synthesis revolutionized global agriculture and industry, but it consumes significant amounts of energy and releases vast quantities of CO 2. One alternative, electrocatalytic nitrogen reduction generally suffers from a low ammonia yield rate and poor selectivity. Here, a tandem "plasma-electrocatalysis" strategy was proposed to harvest ammonia from the air. An ammonia yield rate (~1.43 mg NH3 cm-2 h-1) with almost 100% faradaic efficiency was achieved during over 50 hours of stable operation at -0.33 V vs. RHE. The ammonia yield rate reached up to ~3.0 mg NH3 cm-2 h-1 with a faradaic efficiency of ~62% at -0.63 V vs. RHE. This marked performance is achieved by separating activation of stable nitrogen molecules via non-thermal plasma, followed by selective ammonia synthesis via a cobalt single-atom electrocatalyst. This strategy may rival the Haber-Bosch process and the aspirational electrochemical nitrogen reduction at a distributed small-size ammonia production based on a techno-economic analysis. Plasma-electrocatalysis powered by the renewables offers to produce green ammonia directly from the ubiquitous air, via a unique matter transformation (gas-plasma-liquid). In-depth mechanistic studies revealed the high ammonia yield with nearly 100% faradaic efficiency was achieved by efficient nitrogen activation followed by selective electro-reduction via single-atom Co catalyst. [Display omitted] • Single atom electrocatalysis coupled with plasma jet to generate NH 3 from the air. • NH 3 yield of ~1.43 mgcm-2h-1 at near-unity faradaic efficiency with stability over 50 h. • Profitable NH 3 production at an electricity price of $20/MWh and a small production scale of 1 ton/h. • Vibrational excitation promotes air activation and Co-single atom suppresses H 2 evolution. [ABSTRACT FROM AUTHOR]

Proteins are essential components of human cells and tissues, and they are commonly measured in clinical laboratories using immunoassays. However, these assays have certain limitations, such as non-specificity binding, insufficient selectivity, and interference of antibodies. More sensitive, accurate, and efficient technology is required to overcome these limitations. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a powerful analytical tool that provides high sensitivity and specificity, making it superior to traditional methods such as biochemical methods and immunoassays. While LC-MS/MS has been increasingly used for detecting small molecular analytes and steroid hormones in clinical practice recently, its application for protein or peptide analysis is still in its early stages. Established methods for quantifying proteins and peptides by LC-MS/MS are mainly focused on scientific research, and only a few proteins and peptides can be or have the potential to be detected and applied in clinical practice. Therefore, this article aims to review the clinical applications, advantages, and challenges of analyzing proteins and peptides using LC-MS/MS in clinical laboratories., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To assess the diagnostic value of combining plasma steroid profiling with machine learning (ML) in differentiating between mild autonomous cortisol secretion (MACS) and nonfunctioning adenoma (NFA) in patients with adrenal incidentalomas., Methods: The plasma steroid profiles data in the laboratory information system were screened from January 2021 to December 2023. EXtreme Gradient Boosting was applied to establish diagnostic models using plasma 24-steroid panels and/or clinical characteristics of the subjects. The SHapley Additive exPlanation (SHAP) method was used for explaining the model., Results: Seventy-six patients with MACS and 86 patients with NFA were included in the development and internal validation cohort while the external validation cohort consisted of 27 MACS and 21 NFA cases. Among 5 ML models evaluated, eXtreme Gradient Boosting demonstrated superior performance with an area under the curve of 0.77 using 24 steroid hormones. The SHAP method identified 5 steroids that exhibited optimal performance in distinguishing MACS from NFA, namely dehydroepiandrosterone, 11-deoxycortisol, 11β-hydroxytestosterone, testosterone, and dehydroepiandrosteronesulfate. Upon incorporating clinical features into the model, the area under the curve increased to 0.88, with a sensitivity of 0.77 and specificity of 0.82. Furthermore, the results obtained through SHAP revealed that lower levels of testosterone, dehydroepiandrosterone, low-density lipoprotein cholesterol, body mass index, and adrenocorticotropic hormone along with higher level of 11-deoxycortisol significantly contributed to the identification of MACS in the model., Conclusions: We have elucidated the utilization of ML-based steroid profiling to discriminate between MACS and NFA in patients with adrenal incidentalomas. This approach holds promise for distinguishing these 2 entities through a single blood collection., Competing Interests: Disclosure The authors have no multiplicity of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the effectiveness of non-pharmacologic interventions and the additional benefits of their combination in patients with heart failure with reduced ejection fraction (HFrEF)., Data Sources: We searched PubMed, Embase, and the Cochrane Clinical Trials Register from the date of database inception to April 22, 2023., Study Selection: Randomized controlled trials involving non-pharmacologic interventions conducted in patients with HFrEF were included., Data Extraction: Data were extracted by 2 independent reviewers based on a pre-tested data extraction form. The quality of evidence was assessed using the Cochrane Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation method., Data Synthesis: A total of 82 eligible studies (4574 participants) were included. We performed a random-effects model within a Bayesian framework to calculate weighted mean differences (WMDs) and 95% credibility intervals. High or moderate certainty evidence indicated that high-intensity aerobic interval training (HIAIT) was best on improving 6-minute walk distance (6MWD; 68.55 m [36.41, 100.47]) and left ventricular ejection fraction (6.28% [3.88, 8.77]), while high-intensity aerobic continuous training (HIACT) is best on improving peak oxygen consumption (Peak VO 2 ; 3.48 mL/kg•min [2.84, 4.12]), quality of life (QOL; -17.26 [-29.99, -7.80]), resting heart rate (-8.20 bpm [-13.32, -3.05]), and N-terminal pro-B-type natriuretic peptide (-600.96 pg/mL [-902.93, -404.52]). Moderate certainty evidence supported the effectiveness of inspiratory muscle training to improve peak oxygen consumption and functional electrical stimulation to improve QOL. Moderate-intensity aerobic continuous training (MIACT) plus moderate-intensity resistance training (MIRT) had additional benefits in Peak VO 2 , 6MWD, and QOL. This review did not provide a comprehensive evaluation of adverse events., Conclusions: Both HIAIT and HIACT are the most effective single non-pharmacologic interventions for HFrEF. MIACT plus MIRT had additional benefits in improving peak oxygen consumption, 6MWD, and QOL., (Copyright © 2023 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Over the past decade, advancements in epitranscriptomics have significantly enhanced our understanding of mRNA metabolism and its role in human development and diseases. This period has witnessed breakthroughs in sequencing technologies and the identification of key proteins involved in RNA modification processes. Alongside the well-studied m 6 A, Ψ and m 1 A have emerged as key epitranscriptomic markers. Initially identified through transcriptome-wide profiling, these modifications are now recognized for their broad impact on RNA metabolism and gene expression. In this Perspective, we focus on the detections and functions of Ψ and m 1 A modifications in mRNA and discuss previous discrepancies and future challenges. We summarize recent advances and highlight the latest sequencing technologies for stoichiometric detection and their mechanistic investigations for functional unveiling in mRNA as the new research directions., (© 2024 Zhang et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)