[Relationship between serum 25-hydroxyvitamin D and handgrip strength in middle-aged and elderly people in five cities of Western China].

OBJECTIVE: To explore the association between serum 25-hydroxyvitamin D [25(OH)D] and handgrip strength in middle-aged and elderly people in 5 cities of Western China. METHODS: Based on the data of a cross-sectional survey conducted in the 5 cities of Western China from February to July 2023, the relevant demographic characteristics of people were collected by questionnaire, handgrip strength was collected by physical examination, and serum 25(OH)D was detected by HPLC-MS/MS. The association between the serum 25(OH)D and handgrip strength was analyzed using Logistic regression and Chi-square test for between-group comparisons models. RESULTS: The prevalence of 25(OH)D deficiency and insufficiency among the middle-aged and elderly people in the 5 cities of Western China was 52.9% and 34.5%, respectively. The people who were older, female, and sampled in winter had lower serum 25(OH)D levels (P < 0.05). The prevalence of loss of handgrip strength among the middle-aged and elderly people was 25.3%. The prevalence of handgrip strength loss was higher in the aged 65-80 participants with 25(OH)D deficiency (45. 0%) than in those with 25(OH)D insufficiency (32.6%) and 25(OH)D sufficiency (20.6%). The highest prevalence of loss of handgrip strength was found in the aged 75-80 participants with 25(OH)D deficiency (62. 1%), followed by the 25(OH)D insufficient group (11.1%, P < 0.05). The study found that middle-aged and elderly people with 25(OH)D deficiency had a 1.4-fold increased risk of handgrip strength loss compared with those with 25(OH)D sufficiency (OR=2.403, 95%CI: 1.202-4.804, P=0.013). No significant association was found between 25(OH)D insufficiency and handgrip strength status in the middle-aged and elderly people. For every 5 µg/L increase in total serum 25(OH)D, the risk of handgrip strength loss reduced by 13.1% (OR=0.869, 95%CI: 0.768-0.982, P=0.025). For every 5 µg/L increase in serum 25(OH)D2, the risk of handgrip strength loss reduced by 24.1% (OR=0.759, 95%CI: 0.582-0.990, P=0.042). No significant association was found between serum 25(OH)D3 levels and the risk of handgrip strength loss. The risk of handgrip strength loss in middle-aged and elderly people was reduced by 25.2% for each incremental increase in the total serum 25(OH)D levels (deficient, insufficient and sufficient) (OR=0.748, 95%CI: 0.598-0.936, P=0.011). The risk of handgrip loss was reduced by 40.0% for each incremental increase in serum 25(OH)D levels in the aged 65-80 and aged 65-69 participants, and by 80.0% for each incremental increase in 25(OH)D levels in the aged 75-80 parti-cipants. CONCLUSION: Serum total 25(OH)D and 25(OH)D2 levels are associated with handgrip strength status in middle-aged and elderly people in the 5 cities of Western China.

Advances in contezolid: novel oxazolidinone antibacterial in Gram-positive treatment.

PURPOSE: The principal objective of this project was to review and thoroughly examine the chemical characteristics, pharmacological activity, and quantification methods associated with contezolid. METHODS: The article was based on published and ongoing preclinical and clinical studies on the application of contezolid. These studies included experiments on the physicochemical properties of contezolid, in vitro antimicrobial research, in vivo antimicrobial research, and clinical trials in various phases. There were no date restrictions on these studies. RESULTS: In June 2021, contezolid was approved for treating complicated skin and soft tissue infections. The structural modification of contezolid has resulted in better efficacy compared to linezolid. It inhibits bacterial growth by preventing the production of the functional 70S initiation complex required to translate bacterial proteins. The current evidence has indicated a substantial decline in myelosuppression and monoamine oxidase inhibition without impairing its antibacterial properties. Contezolid was found to have a more significant safety profile and to be metabolised by flavin monooxygenase 5, reducing the risk of harmful effects due to drug-drug interactions. Adjusting doses is unnecessary for patients with mild to moderate renal or hepatic insufficiency. CONCLUSION: As an oral oxazolidinone antimicrobial agent, contezolid is effective against multi-drug resistant Gram-positive bacteria. The introduction of contezolid provided a new clinical option.

Low-Intensity Pulsed Ultrasound: A Physical Stimulus with Immunomodulatory and Anti-inflammatory Potential.

Ultrasound has expanded into the therapeutic field as a medical imaging and diagnostic technique. Low-intensity pulsed ultrasound (LIPUS) is a kind of therapeutic ultrasound that plays a vital role in promoting fracture healing, wound repair, immunomodulation, and reducing inflammation. Its anti-inflammatory effects are manifested by decreased pro-inflammatory cytokines and chemokines, accelerated regression of immune cell invasion, and accelerated damage repair. Although the anti-inflammatory mechanism of LIPUS is not very clear, many in vitro and in vivo studies have shown that LIPUS may play its anti-inflammatory role by activating signaling pathways such as integrin/Focal adhesion kinase (FAK)/Phosphatidylinositol 3-kinase (PI3K)/Serine threonine kinase (Akt), Vascular endothelial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS), or inhibiting signaling pathways such as Toll-like receptors (TLRs)/Nuclear factor kappa-B (NF-κB) and p38-Mitogen-activated protein kinase (MAPK). As a non-invasive physical therapy, the anti-inflammatory and immunomodulatory effects of LIPUS deserve further exploration.

Efficacy and safety of omadacycline for treating complicated skin and soft tissue infections: a meta-analysis of randomized controlled trials.

OBJECTIVE: In the present study, we aimed to compare the clinical efficacy and safety of omadacycline (OMC) with its comparators for the treatment of complicated skin and soft tissue infections (cSSTIs) in adult patients. METHODS: Randomized controlled trials (RCTs) evaluating OMC for cSSTIs were searched in databases of PubMed, Embase, Cochrane, Web of Science, and Clinical Trial, up to July 2022. The primary outcomes were clinical efficacy and microbiological response, with secondary outcome was safety. RESULTS: Four RCTs consisting of 1,757 patients were included, with linezolid (LZD) as a comparator drug. For clinical efficacy, OMC was not inferior to LZD in the modified intent-to-treat (MITT) (OR: 1.24, 95% Cl: [0.93, 1.66], P = 0.15) and clinically evaluable (CE) populations (OR: 1.92, 95% Cl: [0.94, 3.92], P = 0.07). For microbiological response, OMC was numerically higher than LZD in the microbiologically evaluable (ME) (OR: 1.74, 95% Cl: [0.81, 3.74], P = 0.16) and microbiological MITT (micro-MITT) populations (OR: 1.27, 95% Cl: [0.92, 1.76], P = 0.14). No significant difference was found in subpopulations of monomicrobial or polymicrobial mixed infection populations. The mortality and adverse event rates were similar between OMC and LZD. CONCLUSIONS: OMC was as good as LZD in terms of clinical efficacy and microbiological response, and has similar safety issues in treating cSSTIs. OMC might be a promising option for treating cSSTIs in adult patients.

Effects of low-frequency ultrasound combined with anti-MRSA agents on the mouse model of pulmonary infection.

The treatment of methicillin-resistant Staphylococcus aureus (MRSA)-induced pneumonia with antibiotics alone poses considerable challenges. To address these challenges, low-frequency ultrasound (LFU) emerges as a promising approach. In this study, a mouse pneumonia model was established through intratracheal injection of MRSA to investigate the therapeutic efficacy of LFU in combination with antibiotics. Minimal inhibitory concentration was assessed, and the distribution of antibiotics in the lung and plasma was determined using liquid chromatography coupled with mass spectrometry. Various parameters, including the survival rate, histopathology, lung bacterial clearance, and the expressions of cytokines and inflammation-related genes, were evaluated before and after treatment. Compared with the infection group, both the antibiotic-alone groups [vancomycin (VCM), linezolid, and contezolid (CZD)] and the groups in combination with LFU demonstrated an improvement in the survival status of mice. The average colony-forming units of lung tissue in the LFU combination groups were lower compared with the antibiotic-alone groups. While no significant changes in C-reactive protein and procalcitonin in plasma and bronchoalveolar lavage fluid were observed, histopathological results revealed reduced inflammatory damage in LFU combination groups. The secretion of interleukin-6 and tumor necrosis factor-alpha was decreased by the combination treatment, particularly in the VCM + LFU group. Furthermore, the expressions of MRSA virulence factors (hla and agrA) and inflammation-related genes (Saa3, Cxcl9, and Orm1) were further reduced by the combinations of LFU and antibiotics. Additionally, LFU treatment facilitated the distribution of VCM and CZD in mouse lung tissue at 30 and 45 min, respectively, after dosage.IMPORTANCETreating pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) with antibiotics alone poses significant challenges. In this in vivo study, we present compelling evidence supporting the efficacy of low-frequency ultrasound (LFU) as a promising approach to overcome these obstacles. Our findings demonstrated that LFU enhanced the effectiveness of vancomycin, linezolid, and contezolid in an MRSA pneumonia model. The combination of LFU with anti-MRSA agents markedly improved the survival rate of mice, accelerated the clearance of pulmonary bacteria, reduced inflammatory injury, inhibited the production of MRSA endotoxin, and enhanced the distribution of antibiotics in lung tissue. The application of LFU in the treatment of pulmonary infections held substantial significance. We believe that readers of your journal will find this topic of considerable interest.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, and Dose-Increasing Study on the Safety, Tolerability and PK/PD of Multiple Doses of HSK7653 by Oral Administration in Patients with Type 2 Diabetes Mellitus in China.

INTRODUCTION: This study assessed the safety, tolerability, and PK/PD of HSK7653 tablets in Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: This was a Phase IIa, multicenter, randomized, double-blind, placebo-controlled, and dose-increasing study with 48 Chinese diabetes patients. Subjects were randomly assigned to placebo and 10/25/50 mg dose groups, and they received oral administration once every two weeks for a total of six times. Safety and tolerability were assessed throughout this study, and PK/PD parameters were analyzed using non-compartment model with WinNonlin. RESULTS: The three doses of HSK7653 were well tolerated, and the incidence of TEAE and ADR was not significantly increased compared with the placebo group. Cmax increased linearly with the increasing dose, and the mean t1/2 was 64.0-87.0 h. The first dose and last dose PK parameters were similar. After oral administration of 10-50 mg HSK7653 every two weeks, the average Rac_Cmax and Rac_AUC were 0.9-1.0 and 1.0-1.1 respectively; therefore, HSK7653 was not accumulated in vivo. All three doses significantly inhibited DPP-4 activity and increased plasma GLP-1 level and serum insulin levels. When the plasma concentration of HSK7653 was ≥ 20.0 ng/mL, the DPP-4 inhibition rate in all subjects was maintained at > 80.0%. In 10 and 25 mg dose groups, the HbA1c levels maintained a downward trend compared with the placebo group. DISCUSSION: HSK7653 showed desirable pharmacokinetic and pharmacodynamic properties with good safety and tolerability in Chinese T2DM patients. DPP-4 inhibition rate and plasma GLP-1 levels were higher in each dose group than in placebo group. TRIAL REGISTRATION NUMBER: CTR20182505 (Drug Clinical Trial Registration and Information Disclosure Platform, www.chinadrugtrials.org.cn ).

Strategies for starch customization: Agricultural modification.

Raw starch is commonly modified to enhance its functionality for industrial applications. There is increasing demand for 'green' modified starches from both end-consumers and producers. It is well known that environmental conditions are key factors that determine plant growth and yield. An increasing number of studies suggest growth conditions can expand affect starch structure and functionality. In this review, we summarized how water, heat, high nitrogen, salinity, shading, CO2 stress affect starch biosynthesis and physicochemical properties. We define these treatments as a fifth type of starch modification method - agricultural modification - in addition to chemical, physical, enzymatic and genetic methods. In general, water stress decreases peak viscosity and gelatinization enthalpy of starch, and high temperature stress increases starch gelatinization enthalpy and temperature. High nitrogen increases total starch content and regulates starch viscosity. Salinity stress mainly regulates starch and amylose content, both of which are genotype-dependent. Shading stress and CO2 stress can both increase starch granule size, but these have different effects on amylose content and amylopectin structure. Compared with other modification methods, agricultural modification has the advantage of operating at a large scale and a low cost and can help meet the ever-rising market of clean-label foods and ingredients.

Spinach (Spinacia oleracea) microgreen prevents the formation of advanced glycation end products in model systems and breads.

The formation of advanced glycation end products (AGEs) in daily diets poses a great threat to human health, since AGEs are closely related to some chronic metabolic diseases. In this study, we investigated the antiglycative capabilities of some popular microgreens in chemical model. Our data indicated that baby spinach (Spinacia oleracea) had the highest antiglycative activity during 4-wks incubation, with antioxidation being the main action route. Moreover, a bread model was set up to evaluate its antiglycative potential in real food model. The results showed that the fortification of baby spinach in bread significantly inhibited AGEs formation, with acceptable taste and food quality. Further study revealed that the antiglycative components were mainly distributed in leaves, which were separated via column chromatography and tentatively identified as chlorophyll derivatives. In summary, this study highlighted the antiglycative benefits of baby spinach which can be developed into healthy functional foods.

Self-Supervised Deep Multiview Spectral Clustering.

Multiview spectral clustering has received considerable attention in the past decades and still has great potential due to its unsupervised integration manner. It is well known that pairwise constraints boost the clustering process to a great extent. Nevertheless, the constraints are usually marked by human beings. To ameliorate the performance of multiview spectral clustering and alleviate the consumption of human resources, we propose self-supervised multiview spectral clustering with a small number of automatically retrieved pairwise constraints. First, the fused multiple autoencoders are used to extract the latent consistent feature of multiple views. Second, the pairwise constraints are achieved based on the commonality among multiple views. Then, the pairwise constraints are propagated through the neural network with historical memory. Finally, the propagated constraints are used to optimize the fused affinity matrix of spectral clustering. Our experiments on four benchmark datasets show the effectiveness of our proposed approach.

Co-Crystal of Rosiglitazone With Berberine Ameliorates Hyperglycemia and Insulin Resistance Through the PI3K/AKT/TXNIP Pathway In Vivo and In Vitro.

Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by insulin resistance and hyperglycemia. This study examined the effect and elucidated the mechanism of improvement of hyperglycemia and insulin resistance by a co-crystal of rosiglitazone with berberine (RB) in high-sugar high-fat diet (HSHFD)-induced diabetic KKAy mice. Methods: Diabetic KKAy mice were randomly divided into seven groups: KKAy model control group (DM control) treated with 3% sodium carboxymethyl cellulose; RB groups, administered daily with RB 0.7 mg/kg (RB-L), 2.11 mg/kg (RB-M), or 6.33 mg/kg (RB-H); positive control groups, administered daily with rosiglitazone 1.04 mg/kg (RSG), berberine 195 mg/kg (BBR), or combination of 1.04 mg/kg RSG and 1.08 mg/kg BBR (MIX). Test compounds were administered orally for 8 weeks. Non-diabetic C57BL/6J mice were used as normal control (NC). Blood glucose, food intake, body weight, glucose-lipid metabolism, and pathological changes in the pancreas and liver were examined. We further evaluated the mechanism of action of RB in C2C12 and HepG2 cells stimulated with high glucose and palmitate. Results: RB treatment improved glucolipid metabolism and insulin resistance in diabetic KKAy mice. RB reduced blood glucose levels, white fat index, plasma triglyceride (TG), low-density lipoprotein (LDL), gastric inhibitory peptide (GIP), and insulin levels, increased the levels of plasma glucagon-like peptide-1 (GLP-1), high-density lipoprotein (HDL), and glycogen content in the liver and muscle; and improved oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and pathological changes in the pancreas and liver of KKAy mice. Moreover, RB upregulated p-PI3K and p-AKT levels and reduced TXNIP expression in KKAy mice and in HepG2 and C2C12 cells. Conclusion: These data indicate that RB ameliorates insulin resistance and metabolic disorders, and the mechanism might be through regulating the PI3K/AKT/TXNIP signaling pathway . Thus, the co-crystal drug RB may be considered as a potential antidiabetic agent for future clinical therapy.

Effects of supplemental irrigation on winter wheat starch structure and properties under ridge-furrow tillage and flat tillage.

Supplemental irrigation (SI) is an important strategy to improve the water-use efficiency (WUE) of crops without compromising the yield. However, such strategy can influence the starch and grain quality. Hence, the effects of SI on winter wheat starch structure and functionality were studied on ridge-furrow (RF) and flat tillage (FT) treated fields. Flat irrigation was set as control. RF + SI significantly increased the grain yield throughout the study period (2016-2018). SI decreased the amylose content and the content of amylopectin chains with DP 13-24 but increased the proportions of amylopectin chains with DP 6-12 and 25-36. The starch granule relative crystallinity decreased, and more B-type granules were produced by SI treatment. SI significantly increased the resistant starch content in both raw and cooked starch systems. Flat tillage enhanced the effect of SI on granule specific surface area (SSA) and viscosity, which increased starch paste viscosity, while SI + RF showed the opposite effects. Our study demonstrates important combined effects of SI and tillage on wheat starch quality.

Effect of Foliar Application of Various Nitrogen Forms on Starch Accumulation and Grain Filling of Wheat (Triticum aestivum L.) Under Drought Stress.

Foliar nitrogen (N) fertilizer application at later stages of wheat (Triticum aestivum L.) growth is an effective method of attenuating drought stress and improving grain filling. The influences or modes of action of foliar application of various nitrogen forms on wheat growth and grain filling need further research. The objective of this study was to examine the regulatory effects of various forms of foliar nitrogen [NO3 -, NH4 +, and CO(NH2)2] on wheat grain filling under drought stress and to elucidate their underlying mechanisms. The relative effects of each nitrogen source differed in promoting grain filling. Foliar NH4 +-N application notably prolonged the grain filling period. In contrast, foliar application of CO(NH2)2 and NO3 --N accelerated the grain filling rate and regulated levels of abscisic acid (ABA), z-riboside (ZR), and ethylene (ETH) in wheat grains. Analysis of gene expression revealed that CO(NH2)2 and NO3 --N upregulated the genes involved in the sucrose-starch conversion pathway, promoting the remobilization of carbohydrates and starch synthesis in the grains. Besides, activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were increased, whereas the content of malondialdehyde (MDA) declined under foliar nitrogen application (especially NH4 +-N). Under drought stress, enhancement of carbohydrate remobilization and sink strength became key factors in grain filling, and the relative differences in the effects of three N forms became more evident. In conclusion, NH4 +-N application improved the antioxidant enzyme system and delayed photoassimilate transportation. On the other hand, foliar applications of NO3 --N and CO(NH2)2 enhanced sink capacity and alleviated drought stress injury in wheat.

Short-time microwave treatment affects the multi-scale structure and digestive properties of high-amylose maize starch.

Microwave processing is a suitable technology for starch-based food processing. This work investigated the changes of structures and properties of high-amylose maize starch (HAMS) during short-time microwave irradiation (1-4 min). After 1 min of treatment, short amylopectin chains (DP 6-36) and intermediate amylose chains (DP 150-2000) of HAMS were partially broken down. Compared with native HAMS, treated HAMS (1 min) had the higher relative crystallinity, the intensity of the 9 nm lamellar peak, and fluorescence intensity under CLSM. Moreover, 1-min microwaving caused the lower viscosity and higher resistant starch content of HAMS. In the 2-4 min of treatment, the crystallinity, intensity of the lamellar peak and fluorescence intensity of HAMS granules decreased significantly, but no breakdown of starch molecule chains was observed, suggesting the realignment of the crystalline region during the process. Correspondingly, the viscosity increased and resistant starch content decreased. Our study provides a deeper understanding of the mechanistic effects of short-time microwave irradiation on high-amylose starch, which is of value for the processing of HAMS to produce novel functionality and nutritional values.