Effect of multicomponent intervention on malnutrition in older adults: A multicenter randomized clinical trial.

BACKGROUND & AIMS: Malnutrition is a significant geriatric syndrome (GS) prevalent in older adults and seriously affects patient prognosis and quality of life. We assessed the impact of the multicomponent intervention of health education, dietary advice, and exercise with oral nutritional supplementation (ONS) on nutritional status, body composition, physical functions, and quality of life. METHODS: This multicenter randomized clinical trial (RCT) was performed from April 2021 to April 2022. The intervention lasted for 12 weeks, and 99 older adults with malnutrition or at risk of malnutrition were enrolled in six nursing homes. All participants were randomly assigned to the control (health education plus standard diet plus exercise) or research (health education plus standard diet plus exercise plus ONS) group. The research group consumed ONS (244 kcal, 9.8g protein, and 9.6g fat per time) twice a day between meals. The primary outcomes were changes in the nutritional status and body composition from baseline to 12 weeks. The secondary outcomes were changes in physical function, quality of life and nutritional associated other blood markers. RESULTS: For primary outcomes, after 12 weeks, body weight increased similarly in both treatment arms (time × treatment effect, P > 0.05). There were no between-group differences in body mass index (BMI) or mini nutritional assessment tool-short form (MNA-SF) scores (time × treatment effects, P > 0.05). The MNA-SF score from 11.0 (10.5, 12.0) to 13.0 (11.0, 13.0) in the research group and from 11.0 (10.0, 12.0) to 12.0 (11.0, 13.0) in the control group (both P < 0.05). There were no between-group differences in the skeletal muscle mass index (SMI), fat-free mass index (FFMI), appendicular skeletal muscle mass (ASMM), fat mass (FAT), or leg muscle mass (LMM) (time × treatment effects, P > 0.05). Both groups showed similar and highly significant increases in SMI, FFMI, and LMM after (P < 0.05). The research group showed an increase in fat-free mass (FFM) and ASMM and a decrease in the percent of body fat (PBF) and waist circumference (WC) (P < 0.05). For secondary outcomes, There were no between-group differences in grip strength, short physical performance battery (SPPB), 6-min walking distance (6MWD), activities of daily living (ADL), instrumental activities of daily living (IADL), frailty status (FRAIL), mini-mental state examination (MMSE), Tinetti, geriatric depression scale-15 (GDS-15), or 12-item short form survey (SF-12) (time × treatment effects, P > 0.05). Although there was no significant difference, the 6MWD changed differentially between the two treatment arms during the study period in favor of the research group. Although not significant, SF-12 scores improved after 12 weeks in both groups. No between-group differences were observed in prealbumin (PRE), c-reactive protein (CRP), vitamin D (VIT-D), insulin-like growth factor 1 (IGF-1), alanine transaminase (ALT), aspartate aminotransferase (AST), serum creatinine (Scr), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), insulin, and adiponectin levels (time × treatment effects, P > 0.05). Insulin and adiponectin levels were significantly higher in the control group (P < 0.05). CONCLUSION: The twelve-week multicomponent intervention improved the nutritional status of older people in China at risk of malnutrition. ONS may enhance the effects of exercise on muscle mass. This clinical trial was registered (https://www. CLINICALTRIALS: gov). The trial number is ChiCTR2000040343.

The roles and applications of short-chain fatty acids derived from microbial fermentation of dietary fibers in human cancer.

Dietary fibers (DFs) and their metabolites attract significant attention in research on health and disease, attributing to their effects on regulating metabolism, proliferation, inflammation, and immunity. When fermented by gut microbiota, DFs mainly produce short-chain fatty acids (SCFAs), such as acetic acid, propionic acid, and butyric acid. As the essential nutrients for intestinal epithelial cells, SCFAs maintain intestinal homeostasis and play essential roles in a wide range of biological functions. SCFAs have been found to inhibit histone deacetylase, activate G protein-coupled receptors, and modulate the immune response, which impacts cancer and anti-cancer treatment. Notably, while extensive studies have illuminated the roles of SCFAs in colorectal cancer development, progression, and treatment outcomes, limited evidence is available for other types of cancers. This restricts our understanding of the complex mechanisms and clinical applications of SCFAs in tumors outside the intestinal tract. In this study, we provide a comprehensive summary of the latest evidence on the roles and mechanisms of SCFAs, with a focus on butyric acid and propionic acid, derived from microbial fermentation of DFs in cancer. Additionally, we recapitulate the clinical applications of SCFAs in cancer treatments and offer our perspectives on the challenges, limitations, and prospects of utilizing SCFAs in cancer research and therapy.

Antioxidant and In Vivo Hypoglycemic Activities of Ethanol Extract from the Leaves of Engelhardia roxburghiana Wall, a Comparative Study of the Extract and Astilbin.

The leaves of Engelhardia roxburghiana Wall (LERW) has been used as sweet tea in China throughout history. In this study, the ethanol extract of LERW (E-LERW) was prepared and the compositions were identified by HPLC-MS/MS. It indicates that astilbin was the predominant component in E-LERW. In addition, E-LERW was abundant in polyphenols. Compared to astilbin, E-LERW presented much more powerful antioxidant activity. The E-LERW also had stronger affinity with α-glucosidase and exerted more vigorous inhibitory effect on the enzyme. Alloxan-induced diabetic mice had significantly elevated glucose and lipid levels. Treatment with E-LERW at the medium dose (M) of 300 mg/kg could reduce the levels of glucose, TG, TC, and LDL by 16.64%, 12.87%, 32.70%, and 22.99%, respectively. In addition, E-LERW (M) decreased food intake, water intake, and excretion by 27.29%, 36.15%, and 30.93%, respectively. Moreover, E-LERW (M) therapy increased the mouse weight and insulin secretion by 25.30% and 494.52%. With respect to the astilbin control, E-LERW was more efficient in reducing the food and drink consumption and protecting pancreatic islet and body organs from alloxan-induced damage. The study demonstrates that E-LERW may be a promising functional ingredient for the adjuvant therapy of diabetes.

Identification of Potential Factors for the Promotion of Fucoxanthin Synthesis by Methyl Jasmonic Acid Treatment of Phaeodactylum tricornutum.

Fucoxanthin, a vital secondary metabolite produced by marine diatoms, has great economic value and research potential. However, its popularization and application have been greatly restricted due to its low content, difficult extraction, and high production cost. Methyl jasmonic acid (MeJA) exerts similar inductive hormones in the growth and development as well as metabolic processes of plants. In Phaeodactylum tricornutum (P. tricornutum), MeJA treatment can increase fucoxanthin content. In this study, the effects of different concentrations of MeJA on the cell growth and the fucoxanthin content of P. tricornutum were explored. Meanwhile, this study used high-throughput sequencing technology for transcriptome sequencing of P. tricornutum and subsequently performed differential gene expression analysis, gene ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and weighted gene co-expression network analysis (WGCNA) for screening the hub genes for the promotion of fucoxanthin synthesis with MeJA-treated P. tricornutum. On this basis, the functions of the hub genes for the promotion of fucoxanthin synthesis with MeJA-treated P. tricornutum were further analyzed. The results revealed that the carotenoid synthesis-related genes PHATRDRAFT_54800 and PHATRDRAFT_20677 were the hub genes for the promotion of fucoxanthin synthesis with MeJA-treated P. tricornutum. PHATRDRAFT_54800 may be a carotenoid isomerase, while PHATRDRAFT_20677 may be involved in the MeJA-stimulated synthesis of fucoxanthin by exerting the role of SDR family NAD(P)-dependent oxidoreductases.

Fine-Grained Software Defect Prediction Based on the Method-Call Sequence.

Currently, software defect-prediction technology is being extensively researched in the design of metrics. However, the research objects are mainly limited to coarse-grained entities such as classes, files, and packages, and there is a wide range of defects that are difficult to predict in actual situations. To further explore the information between sequences of method calls and to learn the code semantics and syntactic structure between methods, we generated a method-call sequence that retains the code context structure information and the token sequence representing semantic information. We embedded the token sequence into the method-call sequence and encoded it into a fixed-length real-valued vector. We then built a defect-prediction model based on the transformer, which maps the code-vector representation containing the method-call sequences to a low-dimensional vector space to generate semantic features and syntactic structure features and also predicts the defect density of the method-call sequence. We conducted experiments on 10 open-source projects using the ELFF dataset. The experimental results show that the method-call sequence-level prediction effect is better than the class-level effect, and the prediction results are more stable than those of the method level. The mean absolute error (MAE) value of our approach was 8% lower than that of the other deep-learning methods.

An Update on the Immunotherapy for Oropharyngeal Squamous Cell Carcinoma.

Oropharyngeal squamous cell carcinoma (OPSCC) is an uncommon malignancy worldwide. Remarkably, the rising incidence of OPSCC has been observed in many developed countries over the past few decades. On top of tobacco smoking and alcohol consumption, human papillomavirus (HPV) infection has become a major etiologic factor for OPSCC. The radiotherapy-based or surgery-based systemic therapies are recommended equally as first-line treatment, while chemotherapy-based strategy is applied to advanced diseases. Immunotherapy in head and neck squamous cell carcinoma (HNSCC) is currently under the spotlight, especially for patients with advanced diseases. Numerous researches on programmed death-1/programmed death-ligand 1 checkpoint inhibitors have proven beneficial to patients with metastatic HNSCC. In 2016, nivolumab and pembrolizumab were approved as the second-line treatment for advanced metastatic HNSCC by the USA Food and Drug Administration. Soon after, in 2019, the USA Food and Drug Administration approved pembrolizumab as the first-line treatment for patients with unresectable, recurrent, and metastatic HNSCC. It has been reported that HPV-positive HNSCC patients were associated with increased programmed death-ligand 1 expression; however, whether HPV status indicates different treatment outcomes among HNSCC patients treated with immunotherapy has contradicted. Notably, HPV-positive OPSCC exhibits a significantly better clinical response to primary treatment (i.e., radiotherapy, surgery, and chemotherapy) and a more desirable prognosis compared to the HPV-negative OPSCC. This review summarizes the current publications on immunotherapy in HNSCC/OPSCC patients and discusses the impact of HPV infection in immunotherapeutic efficacy, providing an update on the immune landscape and future perspectives in OPSCC.

Better strategies for containing COVID-19 pandemic: a study of 25 countries via a vSIADR model.

We study epidemiological characteristics of 25 early COVID-19 outbreak countries, which emphasizes on the reproduction of infection and effects of government control measures. The study is based on a vSIADR model which allows asymptomatic and pre-diagnosis infections to reflect COVID-19 clinical realities, and a linear mixed-effect model to analyse the association between each country's control measures and the effective reproduction number R t . It finds significant effects of higher stringency measures in lowering the reproduction, and a significant shortening effect on the time to the epidemic turning point by applying stronger early counter measures. Epidemic projections under scenarios of the counter measures (China and Korea, the USA and the UK) show substantial reduction in the epidemic size and death by taking earlier and forceful actions. The governments' response before and after the start of the second wave epidemics were alarmingly weak, which made the average duration of the second wave more than doubled that of the first wave. We identify countries which urgently need to restore to at least the maximum stringency measures implemented so far in the pandemic in order to avoid even higher infection size and death.

A rapid strategy for screening high-efficiency PCSK9 inhibitors from Ginkgo biloba leaves by ligand fishing, HPLC-Q-TOF-MS and interdisciplinary assay.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an attractive target for new cholesterol-lowering drug development. Here, we developed a method integrating ligand fishing, HPLC-Q-TOF-MS and interdisciplinary assay, aiming to explore potential PCSK9 inhibitors from mixtures rapidly and accurately. PCSK9 was expressed and purified firstly, and then the recombined PCSK9 was coated on the surface of magnetic beads (MBs). The PCSK9-immobilized MBs (PCSK9-MBs) were used for ligand fishing combined with HPLC and Q-TOF-MS/MS. Ginkgo biloba leaves (GBL), an herbal medicine widely used in Asia and Europe with good efficacy in treatment of hypercholesterolemia, were chosen as an illustration for ligand fishing. Two PCSK9 ligands were discovered from GBL and identified as kaempferol-3-O-rutinoside (1) and kaempferol 3-O-26″-(6‴-p-coumaroyl) glucosylrhamnoside (KCGR) (2). In order to verify fishing results and pick out more powerful PCSK9 inhibitors, molecular docking assay was further performed and KCGR was optimized to be an excellent PCSK9 inhibitor by the confirmation of affinity and activity bioassay. These results suggested that the developed approach could be applied to screen and analysis potential bioactive constituents from mixtures, which may improve the efficiency of drug discovery. Moreover, KCGR separated from GBL was expected to be a potential candidate of PCSK9 inhibitors.

A New Strategy for Rapidly Screening Natural Inhibitors Targeting the PCSK9/LDLR Interaction In Vitro.

The interaction between proprotein convertase subtilisin/kexin type 9 (PCSK9) and the low-density lipoprotein receptor (LDLR) is a promising target for the treatment of hyperc-holesterolemia. In this study, a new method based on competitive affinity and tag detection was developed, which aimed to evaluate potent natural inhibitors preventing the interaction of PCSK9/LDLR directly. Herein, natural compounds with efficacy in the treatment of hypercholesterolemia were chosen to investigate their inhibitory activities on the PCSK9/LDLR interaction. Two of them, polydatin (1) and tetrahydroxydiphenylethylene-2-O-glucoside (2), were identified as potential inhibitors for the PCSK9/LDLR interaction and were proven to prevent PCSK9-mediated LDLR degradation in HepG2 cells. The results suggested that this strategy could be applied for evaluating potential bioactive compounds inhibiting the interaction of PCSK9/LDLR and this strategy could accelerate the discovery of new drug candidates for the treatment of PCSK9-mediated hypercholesterolemia.