US-guided Percutaneous Radiofrequency Ablation for Secondary Hyperparathyroidism: Long-term Outcomes and Prognostic Factors.

Background Although favorable outcomes have been reported with radiofrequency ablation (RFA) for secondary hyperparathyroidism (SHPT), the long-term efficacy remains insufficiently investigated. Purpose To evaluate the long-term efficacy and safety of US-guided percutaneous RFA in patients with SHPT undergoing dialysis and to identify possible predictors associated with treatment failure. Materials and Methods This retrospective study included consecutive patients with SHPT with at least one enlarged parathyroid gland accessible for RFA who were undergoing dialysis at seven tertiary centers from May 2013 to July 2022. The primary end point was the proportion of patients with parathyroid hormone (PTH) levels less than or equal to 585 pg/mL at the end of follow-up. Secondary end points were the proportion of patients with normal calcium and phosphorus levels, the technical success rate, procedure-related complications, and improvement in self-rated hyperparathyroidism-related symptoms (0-3 ranking scale). The Wilcoxon signed rank test and generalized estimating equation model were used to evaluate treatment outcomes. Univariable and multivariable regression analyses identified variables associated with treatment failure (recurrent or persistent hyperparathyroidism). Results This study included 165 patients (median age, 51 years [IQR, 44-60 years]; 92 female) and 582 glands. RFA effectively reduced PTH, calcium, and phosphorus levels, with targeted ranges achieved in 78.2% (129 of 165), 72.7% (120 of 165), and 60.0% (99 of 165) of patients, respectively, at the end of follow-up (mean, 51 months). For the RFA sessions, the technical success rate was 100% (214 of 214). Median symptom scores (ostealgia, arthralgia, pruritus) decreased (all P < .001). Regarding complications, only hypocalcemia (45.8%, 98 of 214) was common. Treatment failure occurred in 36 patients (recurrent [n = 5] or persistent [n = 31] hyperparathyroidism). The only potential independent predictor of treatment failure was having less than four treated glands (odds ratio, 17.18; 95% CI: 4.34, 67.95; P < .001). Conclusion US-guided percutaneous RFA was effective and safe in the long term as a nonsurgical alternative for patients with SHPT undergoing dialysis; the only potential independent predictor of treatment failure was a lower number (<4) of treated glands. © RSNA, 2024 Supplemental material is available for this article.

Crater-Spectrum Feature Fusion Method for Panax notoginseng Cadmium Detection Using Laser-Induced Breakdown Spectroscopy.

Panax notoginseng (P. notoginseng) is a valuable herbal medicine, as well as a dietary food supplement known for its satisfactory clinical efficacy in alleviating blood stasis, reducing swelling, and relieving pain. However, the ability of P. notoginseng to absorb and accumulate cadmium (Cd) poses a significant environmental pollution risk and potential health hazards to humans. In this study, we employed laser-induced breakdown spectroscopy (LIBS) for the rapid detection of Cd. It is important to note that signal uncertainty can impact the quantification performance of LIBS. Hence, we proposed the crater-spectrum feature fusion method, which comprises ablation crater morphology compensation and characteristic peak ratio correction (CPRC), to explore the feasibility of signal uncertainty reduction. The crater morphology compensation method, namely, adding variables using multiple linear regression (MLR) analysis, decreased the root-mean-square error of the prediction set (RMSEP) from 7.0233 µg/g to 5.4043 µg/g. The prediction results were achieved after CPRC pretreatment using the calibration curve model with an RMSEP of 3.4980 µg/g, a limit of detection of 1.92 µg/g, and a limit of quantification of 6.41 µg/g. The crater-spectrum feature fusion method reached the lowest RMSEP of 2.8556 µg/g, based on a least-squares support vector machine (LSSVM) model. The preliminary results suggest the effectiveness of the crater-spectrum feature fusion method for detecting Cd. Furthermore, this method has the potential to be extended to detect other toxic metals in addition to Cd, which significantly contributes to ensuring the quality and safety of agricultural production.

Increased DNA methylation contributes to the early ripening of pear fruits during domestication and improvement.

BACKGROUND: DNA methylation is an essential epigenetic modification. However, its contribution to trait changes and diversity in the domestication of perennial fruit trees remains unknown. RESULTS: Here, we investigate the variation in DNA methylation during pear domestication and improvement using whole-genome bisulfite sequencing in 41 pear accessions. Contrary to the significant decrease during rice domestication, we detect a global increase in DNA methylation during pear domestication and improvement. We find this specific increase in pear is significantly correlated with the downregulation of Demeter-like1 (DML1, encoding DNA demethylase) due to human selection. We identify a total of 5591 differentially methylated regions (DMRs). Methylation in the CG and CHG contexts undergoes co-evolution during pear domestication and improvement. DMRs have higher genetic diversity than selection sweep regions, especially in the introns. Approximately 97% of DMRs are not associated with any SNPs, and these DMRs are associated with starch and sucrose metabolism and phenylpropanoid biosynthesis. We also perform correlation analysis between DNA methylation and gene expression. We find genes close to the hypermethylated DMRs that are significantly associated with fruit ripening. We further verify the function of a hyper-DMR-associated gene, CAMTA2, and demonstrate that overexpression of CAMTA2 in tomato and pear callus inhibits fruit ripening. CONCLUSIONS: Our study describes a specific pattern of DNA methylation in the domestication and improvement of a perennial pear tree and suggests that increased DNA methylation plays an essential role in the early ripening of pear fruits.

Epigenomic mechanism regulating the quality and ripeness of apple fruit with differing harvest maturity.

Harvest maturity significantly affects the quality of apple fruit in post-harvest storage process. Although the regulatory mechanisms underlying fruit ripening have been studied, the associated epigenetic modifications remain unclear. Thus, we compared the DNA methylation changes and the transcriptional responses of mature fruit (MF) and immature fruit (NF). There were significant correlations between DNA methylation and gene expression. Moreover, the sugar contents (sucrose, glucose, and fructose) were higher in MF than in NF, whereas the opposite pattern was detected for the starch content. The expression-level differences were due to DNA methylations and ultimately resulted in diverse fruit textures and ripeness. Furthermore, the higher ethylene, auxin, and abscisic acid levels in MF than in NF, which influenced the fruit texture and ripening, were associated with multiple differentially expressed genes in hormone synthesis, signaling, and response pathways (ACS, ACO, ZEP, NCED, and ABA2) that were regulated by DNA methylations. Multiple transcription factor genes involved in regulating fruit ripening and quality via changes in DNA methylation were identified, including MIKCC-type MADS-box genes and fruit ripening-related genes (NAP, SPL, WRKY, and NAC genes). These findings reflect the diversity in the epigenetic regulation of gene expression and may be relevant for elucidating the epigenetic regulatory mechanism underlying the ripening and quality of apple fruit with differing harvest maturity.

Whole-genome resequencing of Hu sheep identifies candidate genes associated with agronomic traits.

The phenotypic diversity resulting from artificial or natural selection of sheep has made a significant contribution to human civilization. Hu sheep are a local sheep breed unique to China with high reproductive rates and rapid growth. Genome selection signatures have been widely used to investigate the genetic mechanisms underlying phenotypic variation in livestock. Here, we conduct whole-genome sequencing of 207 Hu sheep and compare them with the wild ancestors of domestic sheep (Asiatic mouflon) to investigate the genetic characteristics and selection signatures of Hu sheep. Based on six signatures of selection approaches, we detect genomic regions containing genes related to reproduction (BMPR1B, BMP2, PGFS, CYP19, CAMK4, GGT5, and GNAQ), vision (ALDH1A2, SAG, and PDE6B), nervous system (NAV1), and immune response (GPR35, SH2B2, PIK3R3, and HRAS). Association analysis with a population of 1299 Hu sheep reveal those missense mutations in the GPR35 (GPR35 g.952651 A>G; GPR35 g.952496 C>T) and NAV1 (NAV1 g.84216190 C>T; NAV1 g.84227412 G>A) genes are significantly associated (P < 0.05) with immune and growth traits in Hu sheep, respectively. This research offers unique insights into the selection characteristics of Hu sheep and facilitates further genetic improvement and molecular investigations.

A new illudane sesquiterpene from the edible fungus Pholiota nameko.

Fungi have different genetic expression abilities and biosynthetic pathways under different cultivation conditions, which can produce various secondary metabolites. The "one strain many compounds" strategy is used to activate silent biosynthetic genes of fungi to produce various compounds, which is an effective method. In order to discover various new compounds in the edible fungus Pholiota nameko, a fermentation strategy involving precursor feeding and enzyme inhibitor addition has been employed. A new illudane sesquiterpene (1), along with one known indole diterpenoid alkaloid, cladosporine A (2) were isolated from the extracts of liquid culture of P. nameko. The new compound was identified by combination of 1D and 2D NMR, MS, optical rotation, and ECD calculations. We conducted experiments on the cytotoxicity of all isolated compounds on three cancer cell lines, but we did not observe any significant cytotoxicity (IC50 > 40 µM).

Identification of Hedyotis diffusa Willd-specific mRNA-miRNA-lncRNA network in rheumatoid arthritis based on network pharmacology, bioinformatics analysis, and experimental verification.

Hedyotis diffusa Willd (HDW) possesses heat-clearing, detoxification, anti-cancer, and anti-inflammatory properties. However, its effects on rheumatoid arthritis (RA) remain under-researched. In this study, we identified potential targets of HDW and collected differentially expressed genes of RA from the GEO dataset GSE77298, leading to the construction of a drug-component-target-disease regulatory network. The intersecting genes underwent GO and KEGG analysis. A PPI protein interaction network was established in the STRING database. Through LASSO, RF, and SVM-RFE algorithms, we identified the core gene MMP9. Subsequent analyses, including ROC, GSEA enrichment, and immune cell infiltration, correlated core genes with RA. mRNA-miRNA-lncRNA regulatory networks were predicted using databases like TargetScan, miRTarBase, miRWalk, starBase, lncBase, and the GEO dataset GSE122616. Experimental verification in RA-FLS cells confirmed HDW's regulatory impact on core genes and their ceRNA expression. We obtained 11 main active ingredients of HDW and 180 corresponding targets, 2150 RA-related genes, and 36 drug-disease intersection targets. The PPI network diagram and three machine learning methods screened to obtain MMP9, and further analysis showed that MMP9 had high diagnostic significance and was significantly correlated with the main infiltrated immune cells, and the molecular docking verification also showed that MMP9 and the main active components of HDW were well combined. Next, we predicted 6 miRNAs and 314 lncRNAs acting on MMP9, and two ceRNA regulatory axes were obtained according to the screening. Cellular assays indicated HDW inhibits RA-FLS cell proliferation and MMP9 protein expression dose-dependently, suggesting HDW might influence RA's progression by regulating the MMP9/miR-204-5p/MIAT axis. This innovative analytical thinking provides guidance and reference for the future research on the ceRNA mechanism of traditional Chinese medicine in the treatment of RA.

Vaccination with Adenovirus Type 5 Vector-Based COVID-19 Vaccine as the Primary Series in Adults: A Randomized, Double-Blind, Placebo-Controlled Phase 1/2 Clinical Trial.

This randomized, double-blind, placebo-controlled phase 1/2 trial aimed at evaluating the safety and immunogenicity of Ad5-nCoV via aerosolized or intramuscular or intramuscular-aerosolized routes in SARS-CoV-2-negative adults aged over 18 years. In the phase 1 trial, participants were sequentially enrolled into one of five regimen cohorts: Low-Dose (two doses of aerosolized Ad5-nCoV with 0.5 × 1010 viral particles [vps] per dose), Middle-Dose (two doses of aerosolized Ad5-nCoV with 1.0 × 1010 vps per dose), High-Dose (two doses of aerosolized Ad5-nCoV with 2.0 × 1010 vps per dose), Mixed (intramuscular Ad5-nCoV with 5.0 × 1010 vps [first dose] and aerosolized Ad5-nCoV with 2.0 × 1010 vps [second dose]), and Single-Dose (one dose of aerosolized Ad5-nCoV with 1.0 × 1010 vps). Eligible participants in the phase 2 trial were stratified by 18-59 years old or ≥60 years old and then were sequentially enrolled into one of six regimen cohorts: Low-Dose, Middle-Dose, High-Dose, Mixed, Single-Dose, and Intramuscular (one dose of intramuscular Ad5-nCoV with 1.0 × 1010 vps). The intervals between the two doses were 56 days. Participants were randomly allocated in 3:1 (phase 1) and 5:1 (phase 2) ratios to receive either Ad5-nCoV or the placebo in each cohort. This study is registered on ClinicalTrials.gov, NCT04840992. Most adverse reactions that occurred during the solicited period were mild and moderate. One serious adverse event (myelodysplastic syndrome) was considered potentially related to the aerosolized Ad5-nCoV. The GMTs of neutralizing antibodies in the Mixed group were the highest with 57.03 (95% CI: 23.95, 135.80) and 97.37 (95% CI: 74.30, 127.59) in phase 1 and 2 trials, respectively, 28 days after the second dose (p < 0.0001), which showed significantly higher immune responses compared to other regimens with aerosolized or intramuscular Ad5-nCoV alone.

Reliability and validity of the Chinese version of the sunlight exposure questionnaire.

Objective: This study aimed to translate and validate the reliability and validity of the Chinese version of the Philippines Sunlight Exposure Questionnaire. Methods: A total of 392 Chinese individuals aged at least 18 years, residing in various cities in Sichuan province for at least 1 year, were recruited. The reliability of the Chinese version of the questionnaire was measured through internal consistency, split-half reliability, and retest reliability, while validity was determined using the content validity index and the structure validity index. Results: The Chinese version of the Sunlight Exposure Questionnaire, which includes 19 items covering 5 factors, demonstrated McDonald's omega coefficient of 0.788. The split-half reliability of the questionnaire was 0.823, and the retest reliability was 0.940. The content validity index (S-CVI) was 0.952. The five-factor structure, supported by eigenvalues, explained 66.2% of the total variance. Confirmatory factor analysis indicated favorable model fit. Results: The chi-square value degrees of freedom ratio (χ2/df) = 1.852, the goodness-of-fit index (GFI) = 0.938, the normed fit index (NFI) = 0.922, the incremental fit index (IFI) = 0.962, the comparative fit index (CFI) = 0.962, the Tucker-Lewis index (TLI) = 0.952, and root mean square error of approximation (RMSEA) = 0.047. The indicators of the fit of the model were within reasonable bounds. Conclusion: The Chinese version of the Sunlight Exposure Questionnaire shows validity and good reliability for assessing sun exposure among adults in a Chinese cultural context.

A label information fused medical image report generation framework.

Medical imaging is an important tool for clinical diagnosis. Nevertheless, it is very time-consuming and error-prone for physicians to prepare imaging diagnosis reports. Therefore, it is necessary to develop some methods to generate medical imaging reports automatically. Currently, the task of medical imaging report generation is challenging in at least two aspects: (1) medical images are very similar to each other. The differences between normal and abnormal images and between different abnormal images are usually trivial; (2) unrelated or incorrect keywords describing abnormal findings in the generated reports lead to mis-communications. In this paper, we propose a medical image report generation framework composed of four modules, including a Transformer encoder, a MIX-MLP multi-label classification network, a co-attention mechanism (CAM) based semantic and visual feature fusion, and a hierarchical LSTM decoder. The Transformer encoder can be used to learn long-range dependencies between images and labels, effectively extract visual and semantic features of images, and establish long-term dependent relationships between visual and semantic information to accurately extract abnormal features from images. The MIX-MLP multi-label classification network, the co-attention mechanism and the hierarchical LSTM network can better identify abnormalities, achieving visual and text alignment fusion and multi-label diagnostic classification to better facilitate report generation. The results of the experiments performed on two widely used radiology report datasets, IU X-RAY and MIMIC-CXR, show that our proposed framework outperforms current report generation models in terms of both natural linguistic generation metrics and clinical efficacy assessment metrics. The code of this work is available online at https://github.com/watersunhznu/LIFMRG.

Prevalence and risk factors for astigmatism in 7 to 19-year-old students in Xinjiang, China: a cross-sectional study.

BACKGROUND: To investigate the prevalence and risk factors for astigmatism in 7-19-year-old students in Xinjiang, China. METHODS: A school-based, cross-sectional study was conducted on students who underwent refraction examination in Xinjiang, China, between May and December 2019. The prevalence of astigmatism was determined. Astigmatism was defined as cylinder power (C) ≤-0.75 D, undefined astigmatism as ≤-1.50 D, and high astigmatism as C ≤-3.00 D. Astigmatism types were: against-the-rule astigmatism (maximum refraction of the main meridian in 180° ± 30°), with-the-rule astigmatism (maximum refraction of the main meridian at 90°±30°), and oblique astigmatism (all other cases). RESULTS: Of the 71,838 students examined (51.0% boys, 7 - 19 years old), 25,945 (36.1%, 95%CI: 35.52-36.68%) had astigmatism and 1267 (1.8%, 95%CI: 1.07-2.53%) had high astigmatism. The prevalence of astigmatism was greater in Han individuals (39.6%) compared with the Hui (34.0%), Kazakh (34.0%), Kyrgyz (32.1%), and Uyghur (26.4%) populations. Among the 25,945 students with astigmatism, 19,947 had with-the-rule astigmatism (76.9%), 3405 had against-the-rule astigmatism (13.1%), and 2593 had oblique astigmatism (10.0%). Multivariable logistic regression analysis showed that ethnicity (Han individuals more susceptible), male gender, age, and refractive errors (myopia and hyperopia) were independently associated with astigmatism, high astigmatism, and with-the-rule astigmatism (all P < 0.05). CONCLUSIONS: The prevalence of astigmatism among children and adolescents in Xinjiang was 36.1%, including 1.8% of high astigmatism. In this population, astigmatism was mainly of the with-the-rule astigmatism type (76.9%). Han ethnicity, male gender, and myopia or hyperopia were independently associated with a high risk of astigmatism.

Automatic detection of thyroid nodules with a real-time artificial intelligence system in a real clinical scenario and the associated influencing factors.

BACKGROUND: At present, most articles mainly focused on the diagnosis of thyroid nodules by using artificial intelligence (AI), and there was little research on the detection performance of AI in thyroid nodules. OBJECTIVE: To explore the value of a real-time AI based on computer-aided diagnosis system in the detection of thyroid nodules and to analyze the factors influencing the detection accuracy. METHODS: From June 1, 2022 to December 31, 2023, 224 consecutive patients with 587 thyroid nodules were prospective collected. Based on the detection results determined by two experienced radiologists (both with more than 15 years experience in thyroid diagnosis), the detection ability of thyroid nodules of radiologists with different experience levels (junior radiologist with 1 year experience and senior radiologist with 5 years experience in thyroid diagnosis) and real-time AI were compared. According to the logistic regression analysis, the factors influencing the real-time AI detection of thyroid nodules were analyzed. RESULTS: The detection rate of thyroid nodules by real-time AI was significantly higher than that of junior radiologist (P = 0.013), but lower than that of senior radiologist (P = 0.001). Multivariate logistic regression analysis showed that nodules size, superior pole, outside (near carotid artery), close to vessel, echogenicity (isoechoic, hyperechoic, mixed-echoic), morphology (not very regular, irregular), margin (unclear), ACR TI-RADS category 4 and 5 were significant independent influencing factors (all P < 0.05). With the combination of real-time AI and radiologists, junior and senior radiologist increased the detection rate to 97.4% (P < 0.001) and 99.1% (P = 0.015) respectively. CONCLUSONS: The real-time AI has good performance in thyroid nodule detection and can be a good auxiliary tool in the clinical work of radiologists.

The Upregulation of Leucine-Rich Repeat Containing 1 Expression Activates Hepatic Stellate Cells and Promotes Liver Fibrosis by Stabilizing Phosphorylated Smad2/3.

Liver fibrosis poses a significant global health risk due to its association with hepatocellular carcinoma (HCC) and the lack of effective treatments. Thus, the need to discover additional novel therapeutic targets to attenuate liver diseases is urgent. Leucine-rich repeat containing 1 (LRRC1) reportedly promotes HCC development. Previously, we found that LRRC1 was significantly upregulated in rat fibrotic liver according to the transcriptome sequencing data. Herein, in the current work, we aimed to explore the role of LRRC1 in liver fibrosis and the underlying mechanisms involved. LRRC1 expression was positively correlated with liver fibrosis severity and significantly elevated in both human and murine fibrotic liver tissues. LRRC1 knockdown or overexpression inhibited or enhanced the proliferation, migration, and expression of fibrogenic genes in the human hepatic stellate cell line LX-2. More importantly, LRRC1 inhibition in vivo significantly alleviated CCl4-induced liver fibrosis by reducing collagen accumulation and hepatic stellate cells' (HSCs) activation in mice. Mechanistically, LRRC1 promoted HSC activation and liver fibrogenesis by preventing the ubiquitin-mediated degradation of phosphorylated mothers against decapentaplegic homolog (Smad) 2/3 (p-Smad2/3), thereby activating the TGF-ß1/Smad pathway. Collectively, these results clarify a novel role for LRRC1 as a regulator of liver fibrosis and indicate that LRRC1 is a promising target for antifibrotic therapies.

Numerical Simulation of Proppant Transport in Major and Branching Fractures Based on CFD-DEM.

This research investigated the effect of branching fracture, proppant, and fracturing fluid on proppant transport based on the CFD-DEM coupling model. The obtained results show that the balance height of embankment in the major fracture decreases gradually with increasing angle between major and branching fractures, while it increases gradually in the branching fracture. This is because the additional resistance of fracturing fluid flow at the joint increases with increasing angle, leading to the decrease of the fracturing fluid velocity. The proppant is prone to settling in branching fractures, resulting in the increase of embankment height in the branching fracture. At angles of 45, 60, and 90°, as the diameter of the proppant increases from 0.8 to 1.1 mm, the balance height of embankment increases slightly in the major fracture, while it decreases in the branching fracture. The frictional resistance of the fracture wall enhances the difficulty of large proppant entering the branching fracture, resulting in a decrease in the amount of proppant entering the branching fracture and a decrease of the balance height of embankment in the branching fracture. In the low-viscosity fracturing fluid, the proppant quickly deposits at the bottom of the fracture as it enters the fracture. Improving the viscosity of the fracturing fluid can significantly enhance its ability to transport the proppant. The proppant is less likely to quickly settle in high-viscosity fracturing fluids, especially when the fracturing fluid viscosity exceeds 50 mPa·s.

The effect of phosphorylation on the conformational dynamics and allostery of the association of death-associated protein kinase with calmodulin.

Protein phosphorylation plays an important role in the signal transduction and is capable of regulation of cell activity. The death-associated protein kinase 1 (DAPK1), as a Ser/Thr kinase, interacts with calmodulin (CaM) to regulate apoptotic and autophagic signaling. Autophosphorylation of DAPK1 at Ser308 located at the autoregulatory domain (ARD) blocks CaM binding and inhibits kinase catalytic activity. However, the mechanism underlying the influence of Ser308 phosphorylation (pS308) on the DAPK1 activity remains unclear. Here, we performed multiple, microsecond length molecular dynamics (MD) simulations, the molecular mechanics generalized Born/surface area (MM-GBSA) binding free energy calculations, principal component analysis, and dynamic cross-correlation analysis to unravel the conformational dynamics and allostery of the DAPK1 - CaM interaction triggered by the pS308 at the ARD. MD simulations showed that pS308 affected the conformational stability of the DAPK1 - CaM complex. Further energetic and structural exploration revealed that pS308 weakened the association of the phosphorylated DAPK1 to CaM, which lowered the susceptibility of DAPK1 to be activated by CaM. This result can provide mechanistic insights into the molecular underpinning through which the DAPK1 kinase activity is modulated by the auto-phosphorylation.Communicated by Ramaswamy H. Sarma.

Preoperative neutrophil-to-lymphocyte ratio predicts symptomatic anastomotic leakage in elderly colon cancer patients: Multicenter propensity score-matched analysis.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), a composite inflammatory biomarker, is associated with the prognosis in patients with colorectal tumors. However, whether the NLR can be used as a predictor of symptomatic postoperative anastomotic leakage (AL) in elderly patients with colon cancer is unclear. AIM: To assess the role of the NLR in predicting the occurrence of symptomatic AL after surgery in elderly patients with colon cancer. METHODS: Data from elderly colon cancer patients who underwent elective radical colectomy with anastomosis at three centers between 2018 and 2022 were retrospectively analyzed. Receiver operating characteristic curve analysis was performed to determine the best predictive cutoff value for the NLR. Twenty-two covariates were matched using a 1:1 propensity score matching method, and univariate and multivariate logistic regression analyses were used to determine risk factors for the development of postoperative AL. RESULTS: Of the 577 patients included, 36 (6.2%) had symptomatic AL. The optimal cutoff value of the NLR for predicting AL was 2.66. After propensity score matching, the incidence of AL was significantly greater in the ≥ 2.66 NLR subgroup than in the < 2.66 NLR subgroup (11.5% vs 2.5%; P = 0.012). Univariate logistic regression analysis revealed statistically significant correlations between blood transfusion intraoperatively and within 2 d postoperatively, preoperative albumin concentration, preoperative prognostic nutritional index, and preoperative NLR and AL occurrence (P < 0.05); multivariate logistic regression analysis revealed that an NLR ≥ 2.66 [odds ratio (OR) = 5.51; 95% confidence interval (CI): 1.50-20.26; P = 0.010] and blood transfusion intraoperatively and within 2 d postoperatively (OR = 2.52; 95%CI: 0.88-7.25; P = 0.049) were risk factors for the occurrence of symptomatic AL. CONCLUSION: A preoperative NLR ≥ 2.66 and blood transfusion intraoperatively and within 2 d postoperatively are associated with a higher incidence of postoperative symptomatic AL in elderly patients with colon cancer. The preoperative NLR has predictive value for postoperative symptomatic AL after elective surgery in elderly patients with colon cancer.

The LiV3 O8 Superlattice Cathode with Optimized Zinc Ion Insertion Chemistry for High Mass-Loading Aqueous Zinc-Ion Batteries.

Resolving the sluggish transport kinetics of divalent Zn2+ in the cathode lattice and improving mass-loading performance are crucial for advancing the zinc-ion batteries (AZIBs) application. Herein, PEO-LiV3 O8 superlattice nanosheets (PEO-LVO) with expanded interlayer spacing (1.16 nm) are fabricated to provide a high-rate, stable lifetime, and large mass-loading cathode. The steady in-plane expansion without shrinkage after the first cycle, but reversible H+ /Zn2+ co-insertion in PEO-LVO are demonstrated by operando synchrotron X-ray diffraction and ex situ characterizations. Moreover, the large capacity of PEO-LVO is traced back to the optimized Zn2+ insertion chemistry with increased Zn2+ storage ratio, which is facilitated by the interlayer PEO in lowering the Zn2+ diffusion barrier and increased number of active sites from additional interfaces, as anticipated by density functional theory. Due to the optimized ion insertion resulting in stalled interfacial byproducts and rapid kinetics, PEO-LVO achieves excellent high mass-loading performance (areal capacity up to 6.18 mAh cm-2 for freestanding electrode with 24 mg cm-2 mass-loading and 2.8 mAh cm-2 at 130 mA cm-2 for conventional electrode with 27 mg cm-2 mass-loading). As a proof-of-concept, the flexible all-solid-state fiber-shaped AZIBs with high mass-loading woven into a fabric can power an electronic watch, highlighting the application potential of PEO-LVO cathode.

Correlation between S100A7 and immune characteristics, methylation, tumor stemness and tumor heterogeneity in pan-cancer and its role in chemotherapy resistance in breast cancer.

OBJECTIVE: To explore the relationships between S100A7 and the immune characteristics, tumor heterogeneity, and tumor stemness pan-cancer as well as the effect of S100A7 on chemotherapy sensitivity in breast cancer. METHODS: TCGA-BRCA and TCGA-PANCANCER RNA-seq data and clinical follow-up survival data were collected from the University of California Santa Cruz database. Survival analyses were performed to explore the relationship between S100A7 expression and pan-cancer prognosis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and Gene Set Enrichment Analysis (GSEA) were used to identify the potential pathways related to the differentially expressed genes in breast cancer. Spearman's and Wilcoxon's tests were used to investigate the relationships between S100A7 expression and immune characteristics, methylation, tumor heterogeneity, and tumor stemness. The potential functions of S100A7 and its influence on chemotherapy sensitivity in breast cancer were elucidated using reverse transcription-quantitative PCR, Cell Counting Kit-8 (CCK-8) assay, Transwell assay, and wound healing assay. RESULTS: S100A7 was highly expressed in most types of tumors and was associated with poor prognosis. S100A7 was closely associated with immunomodulators, immune checkpoint and immune cell infiltration. Further, S100A7 was related to tumor mutational burden, tumor heterogeneity, methylation and tumor stemness in breast cancer. High S100A7 expression was associated with the invasiveness, migration, proliferation and chemotherapy resistance of breast cancer cells in vitro experiments. CONCLUSION: High S100A7 expression was related with poor prognosis and chemotherapy resistance in breast cancer, making it a potential immune and chemotherapy resistance biomarker.

Relationship between sheep feces scores and gastrointestinal microorganisms and their effects on growth traits and blood indicators.

Fecal scores are crucial for assessing the digestive and gastrointestinal status of animals. The Bristol fecal scoring system is a commonly used method for the subjective evaluation of host feces, there is limited research on fecal scoring standards for fattening Hu sheep. In this study, Hu sheep were collected for rumen, rectum, and colon contents for 16S rDNA sequencing. 514 Hu sheep feces were scored based on the Bristol fecal scoring system, and production performance at each stage was measured. Finally, we developed the scoring standard of the manure of Hu sheep in the fattening period (a total of five grades). The result shows that moisture content significantly increased with higher grades (p < 0.05). We analyzed the relationship between fecal scores and production traits, blood indices, muscle nutrients, and digestive tract microorganisms. The growth traits (body weight, body height, body length, average daily gain (ADG), and average daily feed intake (ADFI) during 80-180 days), body composition traits of the F3 group, and the carcass traits were found to be significantly higher (p < 0.05) than those of the F1 and F2 groups. There was no significant difference in gastrointestinal microflora diversity among all groups (p > 0.05). Significant differences were observed in Aspartate aminotransferase, Glucose, Total bilirubin, and Red Blood Cell Count between groups (p < 0.05). The mutton moisture content in group F4 was significantly higher than in the other groups, and the protein content was also the lowest (p < 0.05). The results of the correlation analysis demonstrated that Actinobacteria, Peptostreptococcaceae, Acidaminococcales, Gammaproteobacteria, and Proteobacteria were the significant bacteria affecting fecal scores. In addition, Muribaculaceae and Oscillospiraceae were identified as the noteworthy flora affecting growth performance and immunity. This study highlights the differences in production traits and blood indicators between fecal assessment groups and the complex relationship between intestinal microbiota and fecal characteristics in Hu sheep, suggesting potential impacts on animal performance and health, which suggest strategies for improved management.

MAGL protects against renal fibrosis through inhibiting tubular cell lipotoxicity.

Rationale: Renal fibrosis, with no therapeutic approaches, is a common pathological feature in various chronic kidney diseases (CKD). Tubular cell injury plays a pivotal role in renal fibrosis. Commonly, injured tubular cells exhibit significant lipid accumulation. However, the underlying mechanisms remain poorly understood. Methods: 2-arachidonoylglycerol (2-AG) levels in CKD patients and CKD model specimens were measured using mass spectrometry. 2-AG-loaded nanoparticles were infused into unilateral ureteral obstruction (UUO) mice. Lipid accumulation and renal fibrosis were tested. Furthermore, monoacylglycerol lipase (MAGL), the hydrolyzing enzyme of 2-AG, was assessed in CKD patients and models. Tubular cell-specific MAGL knock-in mice were generated. Moreover, MAGL recombination protein was also administered to unilateral ischemia reperfusion injury (UIRI) mice. Besides, a series of methods including RNA sequencing, metabolomics, primary cell culture, lipid staining, etc. were used. Results: 2-AG was increased in the serum or kidneys from CKD patients and models. Supplement of 2-AG further induced lipid accumulation and fibrogenesis through cannabinoid receptor type 2 (CB2)/ß-catenin signaling. ß-catenin knockout blocked 2-AG/CB2-induced fatty acid ß-oxidation (FAO) deficiency and lipid accumulation. Remarkably, MAGL significantly decreased in CKD, aligning with lipid accumulation and fibrosis. Specific transgene of MAGL in tubular cells significantly preserved FAO, inhibited lipid-mediated toxicity in tubular cells, and finally retarded fibrogenesis. Additionally, supplementation of MAGL in UIRI mice also preserved FAO function, inhibited lipid accumulation, and protected against renal fibrosis. Conclusion: MAGL is a potential diagnostic marker for kidney function decline, and also serves as a new therapeutic target for renal fibrosis through ameliorating lipotoxicity.