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To investigate the functional effects of superfine grinding treatment on Polygonatum cyrtonema Hua powder, in this study, the sample was ground and sieved by pharmacopoeia test sieves (50, 100, 200 and 325 mesh) to prepare P. cyrtonema Hua powder with different particle sizes. Its physical properties were studied using scanning electron microscopy and Fourier transform infrared spectroscopy, while the in vitro gastrointestinal digestion process was simulated. The results showed that the particle size of P. cyrtonema Hua powder exhibited a significant difference (P

Abstract Objective To construct and verify a risk prediction model for sleep disturbance in elderly patients with hypertension, aiming to offer guidance for sleep management in this demographic. Methods A cohort of 6,708 elderly hypertensive patients from the NHANES database, spanning 2005 to 2018, met the inclusion criteria and were selected for this study. Participants were randomly assigned to a development group (n = 4,696) and a verification group (n = 2,012) in a 7:3 ratio. The occurrence of sleep disturbance was assessed across the subjects. Independent risk factors for sleep disturbance were analyzed using weighted multivariate logistic regression within the development group. A predictive model for sleep disturbance risk in elderly hypertensive patients was developed and verified using Stata 17.0. The model's predictive accuracy and stability were evaluated using the verification group's data. Results Of the 6,708 subjects, 2,014 (30.02%) were identified with sleep disturbance, and the weighted prevalence of sleep disturbance among elderly hypertensive patients was 33.283%. Weighted multivariate logistic regression analysis in the development group revealed that six factors were independently associated with sleep disturbance: higher total depression scores, higher education level, asthma, overweight, arthritis, and work restriction (OR > 1 and P

Abstract Background Neighborhood factors of social isolation have been understudied, hindering efforts to reduce social isolation at the neighborhood level. This study aims to investigate the longitudinal effects of neighborhood social cohesion and physical disorder on social isolation in community-dwelling older adults, as well as to examine whether race/ethnicity moderates the neighborhood-isolation relationship. Methods We used 11-year data from the National Health and Aging Trend Study, a longitudinal national study of Medicare beneficiaries aged 65 and older. Social isolation was measured through a summary score across four domains: marital/partner status, family and friend contact, religious attendance, and club participation. A series of weighted mixed-effects logistic regression models were performed to test the study aims. Sample sizes ranged from 7,303 to 7,291 across individual domains of social isolation. Results Approximately 20% of participants reported social isolation. Findings indicated a negative association between neighborhood social cohesion and social isolation. Higher levels of neighborhood social cohesion were longitudinally associated with lower odds of social isolation (odds ratio [OR] = 0.52, 95% CI: 0.47–0.58). Yet, the presence of neighborhood physical disorder was associated with an increased risk of overall social isolation ([OR] = 1.2, 95% CI: 1.00, 1.44). Race/ethnicity significantly moderated the effects of neighborhood social cohesion and physical disorder on social isolation. The odds of no in-person visits associated with neighborhood social cohesion are smaller among Black adults compared to White adults. Black adults had constantly lower odds of isolation from religious attendance compared to White adults regardless of the level of neighborhood social cohesion. Hispanic adults had decreased odds of having no friends associated with signs of physical disorder, while no associations were found among older White adults. White adults had higher odds of isolation from in-person visits when living in neighborhoods with signs of physical disorder, whereas no association was observed among older Black and Hispanic adults. Conclusions This study elucidates the role of neighborhood characteristics in shaping social isolation dynamics among older adults. Furthermore, the observed moderation effects of race/ethnicity suggest the need for culturally sensitive interventions tailored to address social isolation within specific neighborhood and racial contexts.

Abstract In the absence of evidence-based guidance on the impact of hydroxychloroquine (HCQ) blood concentration on efficacy and ocular toxicity in systemic lupus erythematosus (SLE), the clinical monitoring of HCQ blood concentration is not yet widely performed, which raised concerns about the necessity of conducting HCQ blood concentration monitoring. In this retrospective study, we consecutively enrolled 135 patients with SLE who received HCQ treatment for more than 6 months from July 2022 to December 2022. Ocular toxicity was evaluated by collecting relevant retinal parameters using optical coherence tomography angiography (OCTA). Therapeutic efficacy was evaluated using the SLE disease activity index (SLEDAI) and relevant clinical parameters. HCQ blood concentration was determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS). Spearman correlation analysis revealed that the cumulative dose of HCQ was positively correlated with the foveal avascular zone (FAZ) perimeter and FAZ area (r = 0.734, P

Although para-aminosalicylic acid (PAS) has been used to treat tuberculosis for decades, mechanisms of resistance to this drug in Mycobacterium tuberculosis (M. tuberculosis) clinical isolates have not been thoroughly investigated. Previously, we found that decreased methylenetetrahydrofolate reductase (MTHFR) activity of Rv2172c led to increased sensitivity to antifolates in M. tuberculosis. In this study, we collected the genome-sequencing data of 173 PAS-resistant and 803 PAS-sensitive clinical isolates and analyzed rv2172c mutations in those 976 isolates. The results showed that two mutations (T120P and M172V) on rv2172c could be identified in a certain proportion (6.36%) of PAS-resistant isolates. The results of AlphaFold2 prediction indicated that the T120P or M172V mutation might affect the enzymatic activity of Rv2172c by influencing nicotinamide adenine dinucleotide (NADH) binding, and this was verified by subsequent biochemical analysis, demonstrating the role of residues Thr120 and Met172 on NADH binding and enzymatic activity of Rv2172c. In addition, the effect of rv2172c T120P or M172V mutation on methionine production and PAS resistance was determined in M. tuberculosis. The results showed that both T120P and M172V mutations caused increased intracellular methionine concentrations and high level PAS resistance. In summary, we discovered new molecular markers and also a novel mechanism of PAS resistance in M. tuberculosis clinical isolates and broadened the understanding of the NADH-dependent MTHFR catalytic mechanism of Rv2172c in M. tuberculosis, which will facilitate the molecular diagnosis of PAS resistance and also the development of new drugs targeting Rv2172c.

Abstract Background Laparoscopic surgery has been endorsed by clinical guidelines for colon cancer, but not for rectal cancer on account of unapproved oncologic equivalence with open surgery. Aims We started this largest‐to‐date meta‐analysis to comprehensively evaluate the safety and efficacy of laparoscopy in the treatment of rectal cancer compared with open surgery. Materials & Methods Both randomized and nonrandomized controlled trials comparing laparoscopic proctectomy and open surgery between January 1990 and March 2020 were searched in PubMed, Cochrane Library and Embase Databases (PROSPERO registration number CRD42020211718). The data of intraoperative, pathological, postoperative and survival outcomes were compared between two groups. Results Twenty RCTs and 93 NRCTs including 216,615 patients fulfilled the inclusion criteria, with 48,888 patients received laparoscopic surgery and 167,727 patients underwent open surgery. Compared with open surgery, laparoscopic surgery group showed faster recovery, less complications and decreased mortality within 30 days. The positive rate of circumferential margin (RR = 0.79, 95% CI: 0.72 to 0.85, p

Abstract The cell cycle is pivotal to cellular differentiation in plant pathogenic fungi. Cell wall integrity (CWI) signaling plays an essential role in coping with cell wall stress. Autophagy is a degradation process in which cells decompose their components to recover macromolecules and provide energy under stress conditions. However, the specific association between cell cycle, autophagy and CWI pathway remains unclear in model pathogenic fungi Magnaporthe oryzae. Here, we have identified MoSwe1 as the conserved component of the cell cycle in the rice blast fungus. We have found that MoSwe1 targets MoMps1, a conserved critical MAP kinase of the CWI pathway, through protein phosphorylation that positively regulates CWI signaling. The CWI pathway is abnormal in the ΔMoswe1 mutant with cell cycle arrest. In addition, we provided evidence that MoSwe1 positively regulates autophagy by interacting with MoAtg17 and MoAtg18, the core autophagy proteins. Moreover, the S phase initiation was earlier, the morphology of conidia and appressoria was abnormal, and septum formation and glycogen degradation were impaired in the ΔMoswe1 mutant. Our research defines that MoSWE1 regulation of G1/S transition, CWI pathway, and autophagy supports its specific requirement for appressorium development and virulence in plant pathogenic fungi. Video Abstract

Abstract To explore the genetic causal association between pulmonary artery hypertension (PAH) and iron status through Mendelian randomization (MR), we conducted MR analysis using publicly available genome‐wide association study (GWAS) summary data. Five indicators related to iron status (serum iron, ferritin, total iron binding capacity (TIBC), soluble transferrin receptor (sTfR), and transferrin saturation) served as exposures, while PAH was the outcome. The genetic causal association between these iron status indicators and PAH was assessed using the inverse variance weighted (IVW) method. Cochran's Q statistic was employed to evaluate heterogeneity. We assessed pleiotropy using MR‐Egger regression and MR‐Presso test. Additionally, we validated our results using the Weighted median, Simple mode, and Weighted mode methods. Based on the IVW method, we found no causal association between iron status (serum iron, ferritin, TIBC, sTfR, and transferrin saturation) and PAH (pβ > 0.05). The Weighted median, Simple mode, and Weighted mode methods showed no potential genetic causal association (pβ > 0.05 in the three analyses). Additionally, no heterogeneity or horizontal pleiotropy was detected in any of the analyses. Our results show that there are no genetic causal association between iron status and PAH.

The crystal and electronic structures determine a material's physical and chemical properties. Here, using particle swarm optimization method and first-principles calculations, we conducted a systematically investigation on the ordered CuxBey alloys. Two novel stable phase CuxBey (P4¯m2-CuBe3, and I4/mmm-Cu2Be) and five novel metastable CuxBey alloys (F4¯3m-CuBe5, P21/m-CuBe4, P4/mmm-Cu3Be, P4/mmm-Cu4Be, and P4/mmm-Cu5Be) are predicted for the first time. The primary alloying form of ordered CuxBey alloys is the substitution of certain Be atoms for some Cu atoms in the FCC-Cu according to structural study. Obvious valence electrons transfer from Be to Cu and the lattice interstice are observed, which leads to Cu exhibiting negative valence state in CuxBey and Be-rich CuxBey acting as zero-dimensional electrides. Furthermore, these Be-rich CuxBey have good structural stability due to the interaction between interstitial anionic electrons and Be atoms in the Be-tetrahedron. These findings help us in the design and application of CuxBey alloys and related materials.

Abstract Elimination of cancer stem cells (CSCs) and reinvigoration of antitumor immunity remain unmet challenges for cancer therapy. Tumor-associated macrophages (TAMs) constitute the prominant population of immune cells in tumor tissues, contributing to the formation of CSC niches and a suppressive immune microenvironment. Here, we report that high expression of inhibitor of differentiation 1 (ID1) in TAMs correlates with poor outcome in patients with colorectal cancer (CRC). ID1 expressing macrophages maintain cancer stemness and impede CD8+ T cell infiltration. Mechanistically, ID1 interacts with STAT1 to induce its cytoplasmic distribution and inhibits STAT1-mediated SerpinB2 and CCL4 transcription, two secretory factors responsible for cancer stemness inhibition and CD8+ T cell recruitment. Reducing ID1 expression ameliorates CRC progression and enhances tumor sensitivity to immunotherapy and chemotherapy. Collectively, our study highlights the pivotal role of ID1 in controlling the protumor phenotype of TAMs and paves the way for therapeutic targeting of ID1 in CRC.