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Antimicrobial resistance poses an escalating threat to human health, necessitating the development of novel antimicrobial agents capable of addressing challenges posed by antibiotic-resistant bacteria. Thanatin, a 21-amino acid ß-hairpin insect antimicrobial peptide featuring a single disulfide bond, exhibits broad-spectrum antibacterial activity, particularly effective against multidrug-resistant strains. The outer membrane biosynthesis system is recognized as a critical vulnerability in antibiotic-resistant bacteria, which thanatin targets to exert its antimicrobial effects. This peptide holds significant promise for diverse applications. This review begins with an examination of the structure-activity relationship and synthesis methods of thanatin. Subsequently, it explores thanatin's antimicrobial activity, detailing its various mechanisms of action. Finally, it discusses prospective clinical, environmental, food, and agricultural applications of thanatin, offering valuable insights for future research endeavors.

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BACKGROUND: Neurogenic erectile dysfunction, characterized by neurological repair disorders and progressive corpus cavernosum fibrosis (CCF), is an unbearable disease with limited treatment success. IL-17A exhibits a complex role in tissue remodelling. Nevertheless, the precise role and underlying mechanisms of IL-17A in CCF under denervation remain unclear. METHODS: PCR array was employed to identified differentially expressed genes between neurogenic ED and normal rats. IL-17A expression and its main target cells were analyzed using Western blotting, immunofluorescence and immunohistochemistry. The phenotypic regulation of IL-17A on corpus cavernosum smooth muscle cells (CSMCs) was evaluated by cell cycle experiments and SA-ß-Gal staining. The mechanism of IL-17A was elucidated using non-target metabolomics and siRNA technique. Finally, IL-17A antagonist and ABT-263 (an inhibitor of B-cell lymphoma 2/w/xL) were utilized to enhance the therapeutic effect in a rat model of neurogenic ED. RESULTS: IL-17A emerged as the most significantly upregulated gene in the corpus cavernosum of model rats. It augmented the senescence transformation and fibrotic response of CSMCs, and exhibited a strong correlation with CCF. Mechanistically, IL-17A facilitated CCF by activating the mTORC2-ACACA signalling pathway, upregulating of CSMCs lipid synthesis and senescence transition, and increasing the secretion of fibro-matrix proteins. In vivo, the blockade of IL-17A-senescence signalling improved erectile function and alleviated CCF in neurogenic ED. CONCLUSIONS: IL-17A assumes a pivotal role in denervated CCF by activating the mTORC2-ACACA signalling pathway, presenting itself as a potential therapeutic target for effectively overcoming CCF and erection rehabilitation in neurogenic ED.

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Objective: Sarcopenia is a gradually advancing systemic disorder affecting skeletal muscles, primarily distinguished by diminished muscle mass and functional decline. As of present, a universally accepted diagnostic criterion for sarcopenia has yet to be established. From the perspective of the constitution theory in traditional Chinese medicine (TCM), the Yin-deficiency constitution is believed to have a significant correlation with the development of sarcopenia. The primary objective of this study was to examine the potential association between sarcopenia and Yin-deficiency constitution. Methods: The present study is a cross-sectional analysis. The Asian Working Group for Sarcopenia (AWGS) recommended a diagnostic criterion for sarcopenia. A total of 141 participants over 50 years of age were diagnosed with sarcopenia. To determine the constitution of each patient, classification and determination standards were used in traditional Chinese medicine. In this study, a combination of logistic regression and propensity score matching (PSM) was employed to analyze a dataset comprising 1,372 eligible observations. The diagnostic efficacy of the test in distinguishing sarcopenia was assessed through receiver operating characteristic (ROC) curve analysis. Results: The relationship between Yin-deficiency constitution and sarcopenia was examined using logistic regression analysis. In the crude model, the odds ratio (OR) was found to be 3.20 (95% confidence interval [CI]: 1.70-6.03). After adjusting for various confounding factors, including gender, sex, 6 m walking test/(m/s), SMI, and maximum grip strength/kg, the OR increased to 9.70 (95% CI: 3.20-69.38). The associations between seven other biased traditional Chinese medicine (TCM) constitutions and sarcopenia were not found to be statistically significant in the fully adjusted model. The propensity score matching (PSM) analysis yielded consistent results with the logistic regression analysis. Receiver operating characteristic (ROC) curve analysis showed that the AUC of the Yin-deficiency constitution combined with age and gender reached 0.707. Conclusion: Among the nine TCM constitutions examined, the Yin-deficiency constitution demonstrates an independent association with sarcopenia. Yin-deficiency constitution may serve as a potential risk factor for the development of sarcopenia. To establish a causal relationship, further experimental investigations are warranted. The diagnostic performance of sarcopenia is effectively demonstrated by the Yin-deficiency constitution combined with age and gender.

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Objective: Sarcopenia is a geriatric syndrome that occurs with age and is characterized by a gradual decline in muscle mass, power, and functionality. It serves as a prominent contributor to frailty, disability, and mortality among older individuals. Currently, no standardized global guidelines exist for the diagnosis of sarcopenia. This study aimed to establish the correlation between sarcopenia and the constitutions of traditional Chinese medicine (TCM), considering the connection between physical functioning and sarcopenia. Methods: A total of 1441 participants in this study were diagnosed with sarcopenia. The Asian Working Group for Sarcopenia (AWGS) proposed a sarcopenia definition algorithm. To determine the constitution of each participant, classification and determination standards were used in traditional Chinese medicine. This study evaluated the demographics, lifestyles, and self-reported medical history of individuals diagnosed with sarcopenia through a self-administered questionnaire. The constitution of the participants was determined using TCM classification and determination standards. Subsequently, we analyzed the results of univariate analysis and multivariate regression and constructed a receiver operating characteristic (ROC) curve. Results: Participants who were diagnosed with sarcopenia had substantially lower original Neutral constitution scores (P < 0.050). In comparison to those without sarcopenia, individuals with sarcopenia exhibited notably elevated original Qi-deficiency, Yang-deficiency, Yin-deficiency, Blood-stagnation, and Qi-stagnation scores in contrast to those in the healthy group (P < 0.050). The identified risk factors associated with sarcopenia included the following: Neutral (OR = 0.903), Qi-deficiency (in males, OR = 1.126), Yang-deficiency (OR = 1.062), Phlegm-dampness (in males, OR = 0.833), and Blood-stagnation (in females, OR = 1.089). The highest area under the curve (AUC) was observed for the original neutral constitution score, followed by the Yang-deficiency and blood-stagnation scores (0.644, 0.613, and 0.611, respectively). Additionally, the AUC for the combined original scores of all nine constitutions among males reached 0.778. Conclusions: In this cross-sectional study of older people with higher original Qi-deficiency, Yin deficiency, Yang-deficiency, Blood-stagnation, and Qi-stagnation were associated with sarcopenia. Notably, various TCM constitutions are significantly linked to sarcopenia. There was a significant occurrence of various body constitution types among individuals diagnosed with sarcopenia. The mixture of the nine original constitution scores exhibited good diagnostic performance for sarcopenia in males.

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Excited-state intramolecular proton transfer (ESIPT) has attracted great attention in fluorescent sensors and luminescent materials due to its unique photobiological and photochemical features. However, the current structures are far from meeting the specific demands for ESIPT molecules in different scenarios; the try-and-error development method is labor-intensive and costly. Therefore, it is imperative to devise novel approaches for the exploration of promising ESIPT fluorophores. This research proposes an artificial intelligence approach aiming at exploring ESIPT molecules efficiently. The first high-quality ESIPT dataset and a multi-level prediction system are constructed that realized accurate identification of ESIPT molecules from a large number of compounds under a stepwise distinguishing from conventional molecules to fluorescent molecules and then to ESIPT molecules. Furthermore, key structural features that contributed to ESIPT are revealed by using the SHapley Additive exPlanations (SHAP) method. Then three strategies are proposed to ensure the ESIPT process while keeping good safety, pharmacokinetic properties, and novel structures. With these strategies, >700 previously unreported ESIPT molecules are screened from a large pool of 570 000 compounds. The ESIPT process and biosafety of optimal molecules are successfully validated by quantitative calculation and experiment. This novel approach is expected to bring a new paradigm for exploring ideal ESIPT molecules.

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Peptide drugs are becoming star drug agents with high efficiency and selectivity which open up new therapeutic avenues for various diseases. However, the sensitivity to hydrolase and the relatively short half-life have severely hindered their development. In this study, a new generation artificial intelligence-based system for accurate prediction of peptide half-life was proposed, which realized the half-life prediction of both natural and modified peptides and successfully bridged the evaluation possibility between two important species (human, mouse) and two organs (blood, intestine). To achieve this, enzymatic cleavage descriptors were integrated with traditional peptide descriptors to construct a better representation. Then, robust models with accurate performance were established by comparing traditional machine learning and transfer learning, systematically. Results indicated that enzymatic cleavage features could certainly enhance model performance. The deep learning model integrating transfer learning significantly improved predictive accuracy, achieving remarkable R2 values: 0.84 for natural peptides and 0.90 for modified peptides in human blood, 0.984 for natural peptides and 0.93 for modified peptides in mouse blood, and 0.94 for modified peptides in mouse intestine on the test set, respectively. These models not only successfully composed the above-mentioned system but also improved by approximately 15% in terms of correlation compared to related works. This study is expected to provide powerful solutions for peptide half-life evaluation and boost peptide drug development.

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Peptide-based therapeutics hold immense promise for the treatment of various diseases. However, their effectiveness is often hampered by poor cell membrane permeability, hindering targeted intracellular delivery and oral drug development. This study addressed this challenge by introducing a novel graph neural network (GNN) framework and advanced machine learning algorithms to build predictive models for peptide permeability. Our models offer systematic evaluation across diverse peptides (natural, modified, linear and cyclic) and cell lines [Caco-2, Ralph Russ canine kidney (RRCK) and parallel artificial membrane permeability assay (PAMPA)]. The predictive models for linear and cyclic peptides in Caco-2 and RRCK cell lines were constructed for the first time, with an impressive coefficient of determination (R2) of 0.708, 0.484, 0.553, and 0.528 in the test set, respectively. Notably, the GNN framework behaved better in permeability prediction with larger data sets and improved the accuracy of cyclic peptide prediction in the PAMPA cell line. The R2 increased by about 0.32 compared with the reported models. Furthermore, the important molecular structural features that contribute to good permeability were interpreted; the influence of cell lines, peptide modification, and cyclization on permeability were successfully revealed. To facilitate broader use, we deployed these models on the user-friendly KNIME platform (https://github.com/ifyoungnet/PharmPapp). This work provides a rapid and reliable strategy for systematically assessing peptide permeability, aiding researchers in drug delivery optimization, peptide preselection during drug discovery, and potentially the design of targeted peptide-based materials.

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In this work, we present a design concept of introducing linear structures into the orthogonal configuration of 9,9'-spirobifluorene (SBF), aiming to enhance carrier mobilities while maintaining high triplet energies (E T), which are two critical parameters for optimizing host materials in organic light-emitting diodes (OLEDs). To validate our proposed design, four pivotal model molecules of 1,4-diaryl SBFs were synthesized via interannular C-H arylation of bi(hetero)aryl-2-formaldehydes, a task challenging to accomplish using previous synthetic methodologies. The orthogonal configuration and the steric hindrance of SBF lead to high E T through the conjugation breaking at C1 and C4 positions, rendering 1,4-diaryl SBFs suitable as universal pure hydrocarbon (PHC) hosts for red, green, and blue (RGB) phosphorescent OLEDs (PhOLEDs). Meanwhile, the linearity and relatively good planarity of the para-quaterphenyl structure promote high carrier mobilities through orderly intermolecular packing. The synergistic effects of linearity and orthogonality in 1-(para-biphenyl)-4-phenyl-SBF result in exceptional device performance with external quantum efficiencies (EQEs) of 26.0%, 26.1%, and 22.5% for RGB PhOLEDs, respectively. Notably, the green PhOLED exhibits minimal efficiency roll-off, positioning its device performances among the state-of-the-art in PHC hosts.

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Methods for regioselective N-trideuteromethylation of tautomeric polyaza heterocycles are highly sought-after. Disclosed herein is an N-trideuterated methylation reaction of imidazoles and pyrazoles with high regioselectivity and deuterium purity using easily available CF3SO3CD3 as the -CD3 source. This method enables the easy synthesis of important deuterium-labeled azoles, including dimetridazole-d3, ipronidazole-d3, hydroxy dimetridazole-d3, and ronidazole-d3.

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Myocardial ischemia/reperfusion (MI/R) injury is a major cause of adverse outcomes of revascularization following myocardial infarction. Anaerobic glycolysis during myocardial ischemia is well studied, but the role of aerobic glycolysis during the early phase of reperfusion is incompletely understood. Lactylation of Histone H3 (H3) is an epigenetic indicator of the glycolytic switch. Heat shock protein A12A (HSPA12A) is an atypic member of the HSP70 family. In the present study, we report that, during reperfusion following myocardial ischemia, HSPA12A was downregulated and aerobic glycolytic flux was decreased in cardiomyocytes. Notably, HSPA12A KO in mice exacerbated MI/R-induced aerobic glycolysis decrease, cardiomyocyte death, and cardiac dysfunction. Gain- and loss-of-function studies demonstrated that HSPA12A was required to support cardiomyocyte survival upon hypoxia/reoxygenation (H/R) challenge and that its protective effects were mediated by maintaining aerobic glycolytic homeostasis for H3 lactylation. Further analyses revealed that HSPA12A increased Smurf1-mediated Hif1α protein stability, thus increasing glycolytic gene expression to maintain appropriate aerobic glycolytic activity to sustain H3 lactylation during reperfusion and, ultimately, improving cardiomyocyte survival to attenuate MI/R injury.

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Spiking neural networks (SNNs) are brain-inspired models that utilize discrete and sparse spikes to transmit information, thus having the property of energy efficiency. Recent advances in learning algorithms have greatly improved SNN performance due to the automation of feature engineering. While the choice of neural architecture plays a significant role in deep learning, the current SNN architectures are mainly designed manually, which is a time-consuming and error-prone process. In this paper, we propose a spiking neural architecture search (NAS) method that can automatically find efficient SNNs. To tackle the challenge of long search time faced by SNNs when utilizing NAS, the proposed NAS encodes candidate architectures in a branchless spiking supernet which significantly reduces the computation requirements in the search process. Considering that real-world tasks prefer efficient networks with optimal accuracy under a limited computational budget, we propose a Synaptic Operation (SynOps)-aware optimization to automatically find the computationally efficient subspace of the supernet. Experimental results show that, in less search time, our proposed NAS can find SNNs with higher accuracy and lower computational cost than state-of-the-art SNNs. We also conduct experiments to validate the search process and the trade-off between accuracy and computational cost.

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Severe COVID-19 elicits excessive inflammation mediated by innate immune cells like monocytes. Recent evidence reveals extensive epigenetic changes in monocytes during recovery from severe COVID-19, including increased chromatin accessibility at genes related to cytokine production and leukocyte activation. These changes likely originate from the reprogramming of upstream hematopoietic stem and progenitor cells (HSPCs) and represent "trained immunity". HSPC-to-monocyte transmission of epigenetic memory may explain the persistence of these monocyte alterations despite their short lifespan. IL-6 appears pivotal for imprinting durable epigenetic modifications in monocytes during acute infection, with IL-1ß potentially playing a contributory role. The poised inflammatory phenotype of monocytes post-COVID-19 may drive chronic inflammation and tissue damage, contributing to post-acute sequelae of COVID-19 symptoms. COVID-19 could also exacerbate inflammation-related diseases, such multisystem inflammatory syndromes, by altering innate immune tendencies via hematopoietic epigenetic reprogramming. Further clinical investigations quantifying inflammatory mediators and mapping epigenetic changes in HSPCs/monocytes of recovering patients are warranted. Research should also examine whether COVID-19 elicits transgenerational inheritance of epigenetic alterations. Elucidating mechanisms underlying COVID-19-induced monocyte reprogramming and developing interventions targeting key inflammatory regulators like IL-6 may mitigate the sustained inflammatory burden imposed by the aberrant trained immunity post-COVID-19.

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BACKGROUND: Erectile dysfunction (ED) caused by intraoperative nerve injury is a major complication of pelvic surgery. Adipose-derived stem cells (ADSCs) have presented therapeutic potential in a rat model of bilateral cavernous nerve injury (BCNI), while inadequate in vivo viability has largely limited their application. Nuclear factor-E2-related Factor (Nrf2) is a key transcription factor that regulates cellular anti-oxidative stress. In this work, we investigated the effect of Nrf2 expression regulation on the viability of ADSCs, and explore its repair potential in a BCNI rat model. RESULTS: The survival time of tert-Butylhydroquinone (tBHQ)-ADSCs in BCNI model increased obviously. In addition, the tBHQ-ADSCs group presented better restoration of major pelvic ganglion (MPG) nerve contents and fibers, better improvement of erectile function, and less penile fibrosis than the other groups. Moreover, the expression of Nrf2 and superoxide dismutase 1 (SOD1) were higher than those of other groups. CONCLUSION: Nrf2 could enhance the anti-oxidative stress ability of ADSCs, so as to improve the therapeutic effect of ADSCs on BCNI rat model.

RéSUMé: CONTEXTE: La dysfonction érectile (DE) causée par une lésion nerveuse peropératoire est une complication majeure de la chirurgie pelvienne. Les cellules souches dérivées du tissu adipeux (ADSC) ont constitué un potentiel thérapeutique dans un modèle de lésion bilatérale des nerfs caverneux (BCNI) chez le rat, mais une viabilité insuffisante in vivo a largement limité leur application. Nrf2 est un facteur de transcription clé qui régule le stress antioxydant cellulaire. Dans ce travail, nous avons étudié l'effet de la régulation de l'expression de Nrf2 sur la viabilité des ADSC, et exploré son potentiel de réparation dans un modèle de BCNI chez le rat. RéSULTATS: Le temps de survie des cellules tert-butylhydroquinone (tBHQ)-ADSC dans le modèle BCNI a significativement augmenté. De plus, le groupe tBHQ-ADSC a présenté une meilleure restauration du contenu et des fibres nerveuses des ganglions pelviens majeurs, une meilleure amélioration de la fonction érectile et une moindre fibrose pénienne que les autres groupes. Par ailleurs, l'expression de Nrf2 et de la superoxyde dismutase 1 était plus élevée dans ce groupe que dans les autres groupes. CONCLUSIONS: Nrf2 pourrait améliorer la capacité de stress anti-oxydatif des cellules ADSC, améliorant ainsi l'effet thérapeutique des ADSC sur le modèle de BCNI chez le rat.

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The COVID-19 pandemic has uncovered many mysteries about SARS-CoV-2, including its potential to trigger abnormal autoimmune responses. Emerging evidence suggests women may face higher risks from COVID-induced autoimmunity manifesting as persistent neurological symptoms. Elucidating the mechanisms underlying this female susceptibility is now imperative. We synthesize key insights from existing studies on how COVID-19 infection can lead to immune tolerance loss, enabling autoreactive antibodies and lymphocyte production. These antibodies and lymphocytes infiltrate the central nervous system. Female sex hormones like estrogen and X-chromosome mediated effects likely contribute to dysregulated humoral immunity and cytokine profiles among women, increasing their predisposition. COVID-19 may also disrupt the delicate immunological balance of the female microbiome. These perturbations precipitate damage to neural damage through mechanisms like demyelination, neuroinflammation, and neurodegeneration - consistent with the observed neurological sequelae in women. An intentional focus on elucidating sex differences in COVID-19 pathogenesis is now needed to inform prognosis assessments and tailored interventions for female patients. From clinical monitoring to evaluating emerging immunomodulatory therapies, a nuanced women-centered approach considering the hormonal status and immunobiology will be vital to ensure equitable outcomes. Overall, deeper insights into the apparent female specificity of COVID-induced autoimmunity will accelerate the development of solutions mitigating associated neurological harm.

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CONTEXT: Thyroglobulin in needle washout fluid (FNA-Tg) has the advantage of compensating for the low sensitivity of cytological analysis (FNAC) in differentiated thyroid carcinoma (DTC) lymph node (LN) metastasis. However, studies of large data sets to support this view and identify the best cutoff of FNA-Tg are lacking. OBJECTIVE: Our study aimed to determine the best cutoff of FNA-Tg and explore the impact factors of FNA-Tg. METHOD: A total of 1106 suspicious LNs from patients treated at West China Hospital from October 2019 to August 2021 were included. Parameters were compared between metastatic and benign LNs, and the best cutoff value of FNA-Tg was identified by ROC curves. The impact factors of FNA-Tg were analyzed. RESULTS: In the nonsurgery group, after correcting for the effect of age and short diameter of LN, FNA-Tg was the independent risk factor for cervical LN metastasis of DTC (odds ratio [OR]: 1.048; 95% CI, 1.032-1.065). In the surgery group, after correcting for the effects of serum thyrotropin, serum Tg, long diameter of LN, and short diameter of LN, FNA-Tg was the independent risk factor for cervical LN metastasis of DTC (OR: 1.019; 95% CI, 1.006-1.033). The best cutoff value of FNA-Tg was 25.17 µg/L, and the area under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 0.944, 0.847, 0.978, 0.982, 0.819, and 0.902, respectively. FNA-Tg highly correlated with FNA-TgAb (P < .01; Spearman correlation coefficient = 0.559), but FNA-TgAb positivity did not undermine the diagnostic efficacy of FNA-Tg for DTC LN metastasis. CONCLUSION: The best cutoff value of FNA-Tg was 25.17 µg/L in diagnosing DTC cervical LN metastasis. FNA-Tg highly correlated with FNA-TgAb, but FNA-TgAb had no influence on the diagnostic efficacy of FNA-Tg.

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AIM: The incidence and risk factors of low anterior resection syndrome (LARS) largely variate in different studies. In addition, there is lack of study on how patients evaluate the therapeutic effect of LARS. This single-center retrospective study aims to investigate the status of LARS in Chinese patients undergoing laparoscopic low anterior resection (LAR). METHODS: Consequent patients undergoing laparoscopic LAR and free from disease recurrence from January 2015 to May 2021 were issued with both LARS questionnaire and satisfaction survey. Related data were collected and analyzed. RESULTS: Both LARS questionnaires and self-made satisfaction survey were received from 261 eligible patients. The overall incidence of LARS was 47.1% (minor in 19.5%, major in 27.6%), decreased with the passage of postoperative time (64.7% within 12 months, and 41.7% within 12-36 months), and became stable 36 months later (39.7%). The most common symptoms were defecation clustering (n = 107/261, 41.0%) and defecation urgency (n = 101/261, 38.7%). According to the multivariable regression analysis, risk factors of major LARS were: 1 year increase in age (OR 1.035, 95% CI 1.004-1.068), protective stoma (OR 2.656, 95% CI 1.233-5.724) and T3 - 4 stage (OR 2.449, 95% CI 1.137-5.273). Most patients complained defecation disorder (87.3%) to doctors and 84.5% got suggestions or treatments for it. However, only 36.8% patients thought the treatments worked for them. CONCLUSIONS: LARS frequently occurs after laparoscopic LAR, while the therapeutic effect is not satisfying. Elder, advanced T-stage and protective stoma were risk factors for postoperative major LARS.

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BACKGROUND: Sarcopenia is an age-related progressive skeletal muscle disorder involving the loss of muscle mass or strength and physiological function. Efficient and precise AI algorithms may play a significant role in the diagnosis of sarcopenia. In this study, we aimed to develop a machine learning model for sarcopenia diagnosis using clinical characteristics and laboratory indicators of aging cohorts. METHODS: We developed models of sarcopenia using the baseline data from the West China Health and Aging Trend (WCHAT) study. For external validation, we used the Xiamen Aging Trend (XMAT) cohort. We compared the support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGB), and Wide and Deep (W&D) models. The area under the receiver operating curve (AUC) and accuracy (ACC) were used to evaluate the diagnostic efficiency of the models. RESULTS: The WCHAT cohort, which included a total of 4057 participants for the training and testing datasets, and the XMAT cohort, which consisted of 553 participants for the external validation dataset, were enrolled in this study. Among the four models, W&D had the best performance (AUC = 0.916 ± 0.006, ACC = 0.882 ± 0.006), followed by SVM (AUC =0.907 ± 0.004, ACC = 0.877 ± 0.006), XGB (AUC = 0.877 ± 0.005, ACC = 0.868 ± 0.005), and RF (AUC = 0.843 ± 0.031, ACC = 0.836 ± 0.024) in the training dataset. Meanwhile, in the testing dataset, the diagnostic efficiency of the models from large to small was W&D (AUC = 0.881, ACC = 0.862), XGB (AUC = 0.858, ACC = 0.861), RF (AUC = 0.843, ACC = 0.836), and SVM (AUC = 0.829, ACC = 0.857). In the external validation dataset, the performance of W&D (AUC = 0.970, ACC = 0.911) was the best among the four models, followed by RF (AUC = 0.830, ACC = 0.769), SVM (AUC = 0.766, ACC = 0.738), and XGB (AUC = 0.722, ACC = 0.749). CONCLUSIONS: The W&D model not only had excellent diagnostic performance for sarcopenia but also showed good economic efficiency and timeliness. It could be widely used in primary health care institutions or developing areas with an aging population. TRIAL REGISTRATION: Chictr.org, ChiCTR 1800018895.

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Introduction: The Like-Smith (LSM) family plays a critical role in the progression of several cancers. However, the function of LSMs in chemoresistance of gastric cancer (GC) is still elusive. Methods: The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) database and Tumor Immune Estimation Resource Analysis (TIMER) were utilized to analyze the expression, prognostic value and immune infiltration of LSMs in GC patients. Moreover, qPCR and immunohistochemistry (IHC) experiment were conducted with clinical samples. Results: The expression of LSMs was upregulated in GC tissues and most of LSMs were negatively correlated with overall survival of GC patients with 5-fluorouracil (5-FU) treatment. We further revealed that LSM5, 7 and 8 were hub genes of GEO (GSE14210). Besides, the qPCR results demonstrated that a higher level of LSM5 and LSM8 was associated with 5-FU chemoresistance in GC. Moreover, both TIMER and IHC revealed that a lower expression of LSM5 and LSM8 was correlated with high infiltration of T cells, regulatory T cells, B cells, macrophages, and neutrophils. Discussion: Our study systematically investigated the expression pattern and biological features of LSM family members in GC, and identified LSM5 and LSM8 as potential biomarkers in GC with 5-FU chemotherapy.

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OBJECTIVES: To study the factors that influence the 6-minute walking distance (6MWD) among older patients with chronic heart failure. METHODS: This was a single-center, retrospective, observational study. A total of 123 patients from the First Affiliated Hospital of Nanjing Medical University was selected. The factors associated with the 6MWD were analyzed using Pearson correlation analysis and multivariate linear regression. RESULTS: The 6MWD of older patients was negatively correlated with age, fall risk, nutritional score, frailty, and depression but was positively correlated with educational level, fall efficacy, self-care ability, and plasma albumin. The results of independent variable multiple linear regression analysis showed that age (ß = -0.098), fall risk (ß = -0.262), fall efficacy (ß = 0.011), self-care ability (ß = -0.021), nutrition (ß = -0.405), frailty (ß = -0.653), and plasma albumin (ß = 0.127) influenced the 6MWD. CONCLUSIONS: The 6MWD of older patients with chronic heart failure was related to age, self-care ability, fall risk, nutrition, frailty, and depression.

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Objective: To analyze the efficacy of using baseline calcitonin (bCtn) for auxiliary diagnosis of medullary thyroid cancer (MTC) in the hypercalcitoninemic population with thyroid nodules and to explore the relationship between preoperative levels of bCtn and carcinoembryonic antigen (CEA) and MTC staging. Methods: The clinical, pathological, imaging, and lab test data of 58 MTC patients and 84 non-MTC patients were retrospectively reviewed in the study. The patients were hospitalized at West China Hosptal, Sichuan University between 2011 and 2020. Receiver operating characteristic (ROC) curves were constructed to calculate the MTC diagnostic efficacy of bCtn and CEA. The differences in the preoperative bCtn and CEA levels of MTC patients with different primary tumor sites and regional lymph node involvement were compared. Results: The bCtn cutoff values were 31.54 pg/mL for men and 22.60 pg/mL for women for diagnosing MTC in the hypercalcitoninemic population with thyroid nodules. There were statistical differences in preoperative bCtn levels ( H=16.166, P=0.001) and in preoperative CEA levels ( H=9.447, P=0.024) in MTC patients of different T stages. There were statistical differences in preoperative bCtn levels ( H=7.919, P=0.019) and in preoperative CEA levels ( H=7.934, P=0.019) in MTC patients of different N stages. Conclusion: The best bCtn cutoff values for the diagnosis of MTC in the hypercalcitoninemic population with thyroid nodules and are 31.54 pg/mL for men and 22.60 pg/mL for women.

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