Evaluation of the efficacy of chlorhexidine-alcohol vs. aqueous/alcoholic iodine solutions for the prevention of surgical site infections: a systematic review and meta-analysis.

BACKGROUND: Surgical site infection (SSI) is the prevailing complication that occurs after surgery and significantly escalates healthcare expenses. Published meta-analyses and international standards vary in their recommendations for the most effective preoperative skin antiseptic solution and concentration. OBJECTIVE: The aim of this systematic review and meta-analysis is to assess the effectiveness of Chlorhexidine-alcohol compared to Aqueous/alcoholic iodine solutions in preventing post-operative surgical site infections. METHODS: A systematic search was conducted using four electronic databases (PubMed, EMBASE, Scopus, and Cochrane Library) to select publications published in peer-reviewed journals. The risk ratio (RR) was calculated, along with their 95% confidence intervals. We assessed heterogeneity using Cochrane Q and I2 statistics and the appropriate P-value. The analysis used RevMan 5.4. RESULTS: The current meta-analysis includes 14 Randomized controlled trials (RCTs) comparing either 2-2.5% chlorhexidine alcohol with aqueous/alcoholic iodine. It was demonstrated that the CAG-using group had an overall lower incidence of post-operative surgical site infections compared to the iodine-using group (RR=0.30, 95% CI=0.20 to 0.46, I2=95%, P<0.00001). It exhibits comparable efficacy across various surgical procedures, as evidenced by its RR of 0.25 [95% CI 0.15 to 0.41], I2=51%, and P<0.0001 for general surgery, RR=0.47 [95% CI 0.32 to 0.67], I2=82%, P=0.0002 for caesarean section and RR of 0.47 [95% CI 0.34 to 0.65], I2=76% and P<0.00001 for additional surgical procedures, including neurosurgery, orthopedic surgery etc. CONCLUSION: This meta-analysis suggests using either 2·0-2·5% Chlorhexidine in alcohol instead of aqueous, alcoholic iodine to prevent SSIs in adult patients undergoing surgery. Chlorhexidine in alcohol worked effectively for general surgery, cesarean sections, and other surgeries. Thus, preoperative skin cleansing with Chlorhexidine alcohol minimizes postoperative SSIs and bacterial colonization in diverse procedures.

Monoacylglycerol lipase blockades the senescence-associated secretory phenotype by interfering with NF-κB activation and promotes docetaxel efficacy in prostate cancer.

Metabolic reprogramming and cellular senescence greatly contribute to cancer relapse and recurrence. In aging and treated prostate, persistent accumulating senescence-associated secretory phenotype (SASP) of cancer cells often limits the overall survival of patients. Novel strategic therapy with monoacylglycerol lipase (MGLL) upregulation that counters the cellular and docetaxel induced SASP might overcome this clinical challenge in prostate cancer (PCa). With primary comparative expression and survival analysis screening of fatty acid (FA) metabolism signature genes in the TCGA PCa dataset and our single center cohort, MGLL was detected to be downregulated in malignancy prostate tissues and its low expression predicted worse progression-free and overall survival. Functionally, overexpression of MGLL mainly suppresses NF-κB-driven SASP (N-SASP) which mostly restricts the cancer cell paracrine and autocrine tumorigenic manners and the corresponding cellular senescence. Further investigating metabolites, we determined that MGLL constitutive expression prevents lipid accumulation, decreases metabolites preferably, and consequently downregulates ATP levels. Overexpressed MGLL inhibited IκBα phosphorylation, NF-κB p65 phosphorylation, and NF-κB nuclear translocation to deactivate NF-κB transcriptional activities, and be responsible for the repressed N-SASP, partially through reducing ATP levels. Preclinically, combinational treatment with MGLL overexpression and docetaxel chemotherapy dramatically delays tumor progression in mouse models. Taken together, our findings identify MGLL as a switch for lipase-related N-SASP suppression and provide a potential drug candidate for promoting docetaxel efficacy in PCa.

Myrislignan ameliorates the progression of osteoarthritis: An in vitro and in vivo study.

Osteoarthritis (OA) is a prevalent disease of the musculoskeletal system that causes functional deterioration and diminished quality of life. Myrislignan (MRL) has a wide range of pharmacological characteristics, including an anti-inflammatory ability. Although inflammation is a major cause of OA, the role of MRL in OA treatment is still not well-understood. In this study, we analyze the anti-inflammatory and anti-ECM degradation effects of MRL both in vivo and in vitro. Rat primary chondrocytes were treated with interleukin-1ß (IL-1ß) to simulate inflammatory environmental conditions and OA in vitro. The in vivo OA rat model was established by anterior cruciate ligament transection (ACLT) on rat. Our investigation discovered that MRL lowers the IL-1ß-activated tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX2) and inducible nitric-oxide synthase (iNOS) expression in chondrocytes. Moreover, MRL effectively alleviates IL-1ß-induced extracellular matrix (ECM) degradation and promotes ECM synthesis in chondrocytes by upregulating the mRNA level expression of collagen-II and aggrecan (ACAN), downregulating the expression of matrix metalloproteinases-3,-13 (MMP-3, MMP-13), and a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5). Gene expression profiles of different groups identified DEGs that were mainly enriched in functions associated with NF-κB signaling pathway, and other highly enriched in functions related to TNF, IL-17, Rheumatoid arthritis and cytokine-cytokine receptor signaling pathways. Venn interaction of DEGs from the abovementioned five pathways showed that Nfkbia, Il1b, Il6, Nfkb1, Ccl2, Mmp3 were highly enriched DEGs. In addition, our research revealed that MRL suppresses NF-κB and modulates the Nrf2/HO-1/JNK signaling pathway activated by IL-1ß in chondrocytes. In vivo research shows that MRL slows the progression of OA in rats. Our findings imply that MRL might be a viable OA therapeutic choice.

Exposure of Ldlr-/- Mice to a PFAS Mixture and Outcomes Related to Circulating Lipids, Bile Acid Excretion, and the Intestinal Transporter ASBT.

BACKGROUND: Previous epidemiological studies have repeatedly found per- and polyfluoroalkyl substances (PFAS) exposure associated with higher circulating cholesterol, one of the greatest risk factors for development of coronary artery disease. The main route of cholesterol catabolism is through its conversion to bile acids, which circulate between the liver and ileum via enterohepatic circulation. Patients with coronary artery disease have decreased bile acid excretion, indicating that PFAS-induced impacts on enterohepatic circulation may play a critical role in cardiovascular risk. OBJECTIVES: Using a mouse model with high levels of low-density and very low-density lipoprotein (LDL and VLDL, respectively) cholesterol and aortic lesion development similar to humans, the present study investigated mechanisms linking exposure to a PFAS mixture with increased cholesterol. METHODS: Male and female Ldlr-/- mice were fed an atherogenic diet (Clinton/Cybulsky low fat, 0.15% cholesterol) and exposed to a mixture of 5 PFAS representing legacy, replacement, and emerging subtypes (i.e., PFOA, PFOS, PFHxS, PFNA, GenX), each at a concentration of 2mg/L, for 7 wk. Blood was collected longitudinally for cholesterol measurements, and mass spectrometry was used to measure circulating and fecal bile acids. Transcriptomic analysis of ileal samples was performed via RNA sequencing. RESULTS: After 7 wk of PFAS exposure, average circulating PFAS levels were measured at 21.6, 20.1, 31.2, 23.5, and 1.5µg/mL in PFAS-exposed females and 12.9, 9.7, 23, 14.3, and 1.7µg/mL in PFAS-exposed males for PFOA, PFOS, PFHxS, PFNA, and GenX, respectively. Total circulating cholesterol levels were higher in PFAS-exposed mice after 7 wk (352mg/dL vs. 415mg/dL in female mice and 392mg/dL vs. 488mg/dL in male mice exposed to vehicle or PFAS, respectively). Total circulating bile acid levels were higher in PFAS-exposed mice (2,978 pg/µL vs. 8,496 pg/µL in female mice and 1,960 pg/µL vs. 4,452 pg/µL in male mice exposed to vehicle or PFAS, respectively). In addition, total fecal bile acid levels were lower in PFAS-exposed mice (1,797 ng/mg vs. 682 ng/mg in females and 1,622 ng/mg vs. 670 ng/mg in males exposed to vehicle or PFAS, respectively). In the ileum, expression levels of the apical sodium-dependent bile acid transporter (ASBT) were higher in PFAS-exposed mice. DISCUSSION: Mice exposed to a PFAS mixture displayed higher circulating cholesterol and bile acids perhaps due to impacts on enterohepatic circulation. This study implicates PFAS-mediated effects at the site of the ileum as a possible critical mediator of increased cardiovascular risk following PFAS exposure. https://doi.org/10.1289/EHP14339.

Disentangling the Inverse LDL-C-hemorrhagic Stroke Association in Chinese Adults with Hypertension: Findings from the Chinese Multi-Provincial Cohort Study.

Why lower low-density lipoprotein cholesterol (LDL-C) was associated with a decreased atherosclerotic cardiovascular disease (ASCVD) risk but an increased hemorrhagic stroke (HS) risk in hypertensive adults remains unclear. We examined whether the inverse LDL-C-HS association partly arises from its effect on ASCVD. We estimated separable effects of LDL-C on HS outside (i.e., separable direct effect) or only through its effect on ASCVD (i.e., separable indirect effect) in hypertensive adults from the Chinese Multi-provincial Cohort Study. We quantified such effects using numbers needed to treat (NNT) to prevent or cause an extra HS based on the restricted mean event-free time till a 25-year follow-up. LDL-C $<$ 70 mg/dL was not associated with an increased HS risk compared to LDL-C $\ge$ 70 mg/dL regarding total and separable direct effects. However, a small separable indirect effect (i.e., NNT to harm: 9722 participants) was noted and validated via a series of sensitivity analyses. Moreover, modified effects were observed, particularly in the 35-49-year age group, men, and those with SBP $\ge$ 140 mm Hg. These results suggest the inverse LDL-C-HS association in hypertensive adults is partly due to its effect on ASCVD. A better understanding of such associations would provide more enlightening into stroke prevention.

Transformer-based AI technology improves early ovarian cancer diagnosis using cfDNA methylation markers.

Epithelial ovarian cancer (EOC) is the deadliest women's cancer and has a poor prognosis. Early detection is the key for improving survival (a 5-year survival rate in stage I/II is over 70% compared to that of 25% in stage III/IV) and can be achieved through methylation markers from circulating cell-free DNA (cfDNA) using a liquid biopsy. In this study, we first identify top 500 EOC markers differentiating EOC from healthy female controls from 3.3 million methylome-wide CpG sites and validated them in 1,800 independent cfDNA samples. We then utilize a pretrained AI transformer system called MethylBERT to develop an EOC diagnostic model which achieves 80% sensitivity and 95% specificity in early-stage EOC diagnosis. We next develop a simple digital droplet PCR (ddPCR) assay which archives good performance, facilitating early EOC detection.

Identification of candidate genes associated with primary feathers of tianfu nonghua ducks based on Genome-wide association studies.

The primary feathers of ducks have important economic value in the poultry industry. This study quantified the primary feather phenotype of Nonghua ducks, including the primary feathers' length, area, distribution of black spots, and feather symmetry. And genome-wide association analysis was used to screen candidate genes that affect the primary feather traits. The genome-wide association study (GWAS) results identified the genetic region related to feather length (FL) on chromosome 2. Through Linkage disequilibrium (LD) analysis, candidate regions (chr2: 115,246,393-116,501,448 bp) were identified and were further annotated to 5 genes: MRS2, GPLD1, ALDH5A1, KIAA0319, and ATP9B. Secondly, candidate regions related to feather black spots were identified on chromosome 21. Through LD analysis, the candidate regions (chr21: 163,552-2,183,853 bp) were screened and further annotated to 47 genes. Among them, STK4, CCN5, and YWHAB genes were related to melanin-related pathways or pigment deposition, which may be key genes affecting the distribution of black spots on feathers. In addition, we also screened 125 genes on multiple chromosomes that may be related to feather symmetry. Among them, significant SNPs on chromosome 1 were further identified as candidate regions (chr1: 142,118,209-142,223,605 bp) through LD analysis and annotated into 2 genes, TGFBRAP1 and LOC113839965. These results reported the genetic basis of the primary feather from multiple phenotypes, and offered valuable insights into the genetic basis for the growth and development of duck feathers and feather color pattern.

Comparing clinical outcomes of patients with severe lower limb trauma undergoing orthoplastic and orthopedic surgeries: A long-term study protocol.

This long-term study protocol aims to compare the clinical outcomes of patients with severe lower limb trauma undergoing orthoplastic and orthopedic surgeries, focusing on their physical and psychological status. Patients with lower limb injuries and open fractures have been recruited since October 2019 and will be followed up until October 2024. The patients will be divided into two groups: (1) Orthoplastic group, where single-stage debridement, fixation, and soft tissue repair will be performed, and (2) Orthopedic group, where soft tissue repair will be done in a delayed-stage. The follow-up period will be one year, during which clinical data, limb function recovery, psychological scores, and health-related quality of life (HRQOL) will be evaluated to assess postoperative recovery and clinical outcomes. Additional clinical data, such as socio-demographic information, baseline features, Enneking score, Visual Analogue Scale (VAS) score, two-point discrimination score, and blood test parameters will also be collected. The 36-Item Short Form Health Survey (SF-36) will be used to evaluate HRQOL, while the Post-traumatic Stress Disorder Checklist (PCL) will assess the severity of self-reported post-traumatic stress disorder. The results of this study will provide valuable insights into prognostically relevant targets and contribute to improving the management and outcomes of patients with lower limb injuries and open fractures, who often face challenges related to limb disability and potential amputation postoperatively, significantly impacting their psychological and physical well-being.

Single cell analyses reveal the PD-1 blockade response-related immune features in hepatocellular carcinoma.

Background: Immunotherapy has demonstrated its potential to improve the prognosis of patients with hepatocellular carcinoma (HCC); however, patients' responses to immunotherapy vary a lot. A comparative analysis of the tumor microenvironment (TME) in responders and non-responders is expected to unveil the mechanisms responsible for the immunotherapy resistance and provide potential treatment targets. Methods: We performed sequencing analyses using 10x Genomics technology on six HCC patients who responded to anti-PD-1 therapy and one HCC patient who did not respond. Additionally, we obtained single cell data from untreated, responsive, and nonresponsive HCC patients from public databases, and used part of the datasets as a validation cohort. These data were integrated using algorithms such as Harmony. An independent validation cohort was established. Furthermore, we performed spatial transcriptomic sequencing on the tumor adjacent tissues of three HCC responsive patients using 10x Genomics spatial transcriptomic technology. Additionally, we analyzed data about three HCC patients obtained from public databases. Finally, we validated our conclusions using immunofluorescence, flow cytometry, and in vivo experiments. Results: Our findings confirmed the presence of "immune barrier" partially accounting for the limited efficacy of immunotherapy. Our analysis revealed a significant increase in TREM2+ Macrophages among non-responsive patients expressing multiple immunosuppressive signals. anti-Csf1r monoclonal antibodies effectively eliminated these macrophages and augmented the therapeutic effects of anti-PD-1 therapy. TCR+ Macrophages possessed direct tumor-killing capabilities. IL1B+ cDC2 was the primary functional subtype of cDC2 cells. Absence of THEMIShi CD8+ T subtypes might diminish immunotherapeutic effects. Furthermore, CD8+ T cells entered a state of stress after anti-PD-1 treatment, which might be associated with CD8+ T cell exhaustion and senescence. Conclusions: The profiles of immune TMEs showed differences in HCC patients responsive, non-responsive and untreated. These differences might explain the discounted efficacy of immunotherapy in some HCC patients. The cells and molecules, which we found to carry unique capabilities, may be targeted to enhance immunotherapeutic outcomes in patients with HCC.

The effect of probiotics supplementation on cancer-treatment complications: a critical umbrella review of interventional meta-analyses.

Cancer-related complications pose significant challenges in the management and treatment of patients with malignancies. Several meta-analyses have indicated improving effects of probiotics on cancer complications, while some studies have reported contentious findings. The purpose of the present study was to evaluate the efficacy of probiotics in addressing cancer complications, including diarrhea, mucositis, and infections, following chemotherapy, radiotherapy, and surgery. Relevant studies were searched in the PubMed, Scopus, Embase and Web of Science databases and Google Scholar up to September 2023. All meta-analyses addressing the effects of probiotics on all cancer treatments-induced complications including infection, diarrhea and oral mucositis were included. The pooled results were calculated using a random-effects model. Analyses of subgroups, sensitivity and publication bias were also conducted. The results revealed that the probiotics supplementation was effective on reduction of total cancer complications (OR:0.53; 95% CI: 0.44, 0.62, p < 0.001; I2=79.0%, p < 0.001), total infection rate (OR:0.47; 95%CI: 0.41, 0.52, p < 0.001; I2= 48.8%, p < 0.001); diarrhea (OR:0.50; 95%CI: 0.44, 0.57, p < 0.001; I2=44.4%, p = 0.023) and severe diarrhea (OR: 0.4; 95%CI: 0.27, 0.56, p < 0.001; I2=31.3%, p = 0.178), oral mucositis (OR: 0.76; 95%CI: 0.58, 0.94, p < 0.001; I2=95.5%, p < 0.001) and severe oral mucositis (OR:0.65, 95%CI: 0.58, 0.72 p < 0.001; I2=22.1%, p = 0.274). Multi strain probiotic (OR:0.49; 95%CI: 0.32, 0.65, p < 0.001; I2=90.7%, p < 0.001) were more efficacious than single strain (OR:0.73; 95%CI: 0.66, 0.81, p < 0.001; I2=0.00%, p = 0.786). The findings of the current umbrella meta-analysis provide strong evidence that probiotic supplementation can reduce cancer complications.

The First Discovery of Spherical Carborane Molecular Ferroelectric Crystals.

Carborane compounds, known for their exceptional thermal stability and non-toxic attributes, have garnered widespread utility in medicine, supramolecular design, coordination/organometallic chemistry, and others. Although there is considerable interest among chemists, the integration of suitable carborane molecules into ferroelectric materials remains a formidable challenge. In this study, we employ the quasi-spherical design strategy to introduce functional groups at the boron vertices of the o-carborane cage, aiming to reduce molecular symmetry. This approach led to the successful synthesis of the pioneering ferroelectric crystals composed of cage-like carboranes: 9-OH-o-carborane (1) and 9-SH-o-carborane (2), which undergo above-room ferroelectric phase transitions (Tc) at approximately 367 K and 347 K. Interestingly, 1 and 2 represent uniaxial and multiaxial ferroelectrics respectively, with 2 exhibiting six polar axes and as many as twelve equivalent polarization directions. As the pioneering instance of carborane ferroelectric crystals, this study introduces a novel structural archetype for molecular ferroelectrics, thereby providing fresh insights into the exploration of molecular ferroelectric crystals with promising applications.

Single-cell analysis defines LGALS1 + fibroblasts that promote proliferation and migration of intrahepatic cholangiocarcinoma.

The incidence rate of intrahepatic cholangiocarcinoma (ICC), which has a poor prognosis, is rapidly increasing. To investigate the intratumor heterogeneity of ICC, we analyzed single-cell RNA sequencing data from the primary tumor and adjacent normal tissues of 14 treatment-naïve patients. We identified ten major cell types, along with 45 subclusters of cells. Notably, we identified a fibroblast cluster, Fibroblast_LUM+, which was preferably enriched in tumor tissues and actively interacted with cholangiocytes. LGALS1 was verified as a marker gene of Fibroblast_LUM+, contributing to the malignant phenotype of ICC. The higher amount of LGALS1 + fibroblasts were associated with poorer overall survival in ICC patients. LGALS1 + fibroblasts activated the proliferation and migration of tumor cells by upregulating the expression levels of CCR2, ADAM15, and ß-integrin. Silencing LGALS1 in cancer-associated fibroblasts (CAFs) suppressed CAF-augmented tumor cell migration and invasion in vitro as well as tumor formation in vivo, suggesting that blockade of LGALS1 serves as a potential therapeutic approach for ICC. Taken together, our single-cell analysis provides insight into the interaction between malignant cells and specific subtypes of fibroblasts. Our work will further the understanding of the intratumor heterogeneity of ICC and provide novel strategies for the treatment of ICC by targeting fibroblasts in the tumor microenvironment.

Using ozone nanobubbles, and microalgae to promote the removal of nutrients from aquaculture wastewater: Insights from the changes of microbiomes.

Integrated aquaculture wastewater treatment systems (IAWTSs) are widely used in treating aquaculture wastewater with the aeration-microalgae unit serving as an important component. In this study, we artificially constructed an IAWTS and applied two aeration-microalgae methods: ordinary aeration or ozone nanobubbles (ONBs) with microalgae (Nannochloropsis oculata). The impact of N.oculata and ONBs on the removal performance of nutrients and the underlying micro-ecological mechanisms were investigated using 16S rRNA gene amplicon sequencing. The results demonstrated that the combined use of ONBs and N.oculata exhibited superior purification effects with 78.25%, 76.59% and 86.71% removal of CODMn, TN and TP. N.oculata played a pivotal role as the primary element in wastewater purification, while ONBs influenced nutrient dynamics by affecting both N.oculata and bacterial communities. N.oculata actively shaped bacterial communities, with a specific focus on nitrogen and phosphorus cycling in the micro-environment remodeled by ONBs. Rare bacterial communities displayed heightened activity in response to the changes in N.oculata, ONBs, and nutrient levels. These findings provide a novel approach to improve the technological processes the IAWTS, contributing to the advancement of sustainable aquaculture practices by offering valuable insights into wastewater purification efficiency and micro-ecological mechanisms.

Structure and dynamics of microbial communities associated with the resurrection plant Boea hygrometrica in response to drought stress.

MAIN CONCLUSION: The resurrection plant Boea hygrometrica selectively recruits and assembles drought-specific microbial communities across the plant-soil compartments, which may benefit plant growth and fitness under extreme drought conditions. Plant-associated microbes are essential for facilitating plant growth and fitness under drought stress. The resurrection plant Boea hygrometrica in natural habitats with seasonal rainfall can survive rapid desiccation, yet their interaction with microbiomes under drought conditions remains unexplored. This study examined the bacterial and fungal microbiome structure and drought response across plant-soil compartments of B. hygrometrica by high-throughput amplicon sequencing of 16S rRNA gene and internal transcribed spacer. Our results demonstrated that the diversity, composition, and functional profile of the microbial community varied considerably across the plant-soil compartments and were strongly affected by drought stress. Bacterial and fungal diversity was significantly reduced from soil to endosphere and belowground to aboveground compartments. The compartment-specific enrichment of the dominant bacteria phylum Cyanobacteriota and genus Methylorubrum in leaf endosphere, genera Pseudonocardia in rhizosphere soil and Actinoplanes in root endosphere, and fungal phylum Ascomycota in the aboveground compartments and genera Knufia in root endosphere and Cladosporium in leaf endosphere composed part of the core microbiota with corresponding enrichment of beneficial functions for plant growth and fitness. Moreover, the recruitment of dominant microbial genera Sphingosinicella and Plectosphaerella, Ceratobasidiaceae mycorrhizal fungi, and numerous plant growth-promoting bacteria involving nutrient supply and auxin regulation was observed in desiccated B. hygrometrica plants. Our results suggest that the stable assembled drought-specific microbial community of B. hygrometrica may contribute to plant survival under extreme environments and provide valuable microbial resources for the microbe-mediated drought tolerance enhancement in crops.

Impact of Sacubitril/Valsartan on Cardiac Structure and Blood Levels of miRNA-328 and NT-proBNP in Patients with CHD and Chronic Heart Failure.

Objective: This study specifically investigates the impact of sacubitril/valsartan on cardiac structural remodeling and modulation of blood levels of miRNA-328 and NT-proBNP in patients with coronary heart disease (CHD) complicated by chronic heart failure (CHF). We aim to determine whether sacubitril/valsartan offers advantages over traditional therapies regarding cardiac morphology and molecular biomarkers, thus providing insights into its potential role in managing CHD and CHF. Methods: From January 2020 to January 2023, CHD patients with chronic heart failure were randomized into two groups for this study. Both groups received standard treatments: the control group received valsartan, while the study group received sacubitril/valsartan. Therapeutic outcomes were analyzed, including changes in cardiac structure, function, miRNA-328, and NT-proBNP levels in the blood, along with noting any adverse reactions. Results: The total effective rate in the study group was 86.67%, significantly higher than that in the control group (71.67%) (P < .05). After treatment, both groups exhibited reductions in left atrial anterior and posterior diameter, left ventricular end-diastolic diameter, and left ventricular end-systolic diameter compared to before treatment, with the study group showing lower values than the control group (P < .05). The left ventricular ejection fraction (LVEF) increased in both groups, with the study group showing a higher increase than the control group. Additionally, the end-diastolic volume and end-systolic volume decreased in both groups after treatment, with the study group showing greater decreases than the control group (P < .05). Moreover, both groups exhibited reductions in peripheral blood levels of miRNA-328 and NT-proBNP, with the study group showing greater reductions than the control group (P < .05). There was no significant difference in the incidence of adverse reactions between the study group and the control group during treatment (P > .05). Conclusion: Sacubitril/valsartan significantly improves cardiac function and structure in patients with CHD complicated by CHF, effectively reducing levels of miRNA-328 and NT-proBNP in the blood. It demonstrates safety and high value in clinical applications.

High Performance Mg Alloy with Designed Microstructure and Phases.

A high strength and ductile Mg-Gd-Y-Zn-Zr alloy was designed and fabricated. The local strain evolution of the alloys during plastic deformation was analyzed using high-resolution digital image correlation (DIC). The results showed that the ß particles, nano-sized γ' phases, and LPSO phases were distributed in the as-extruded alloy and a bimodal microstructure was exhibited, including elongated un-dynamic recrystallized grains and fine dynamic recrystallized grains. With increasing extrusion ratio, the grain size remained, with the volume fraction of dynamic recrystallization of the as-extruded alloy increasing from 30% to 75%, and the as-extruded alloy exhibited a high strength-ductility synergy, which is attributed to the grain refinement, extensive ß particles, and elongated block-shaped LPSO phases. The strain evolution analysis showed that a strain-transfer from un-DRXed regions to adjacent DRXed regions and LPSO phases can promote uniform plastic deformation, which tends to improve the ductility of the alloy.

Regioselective 1,4-/1,3-Difunctionalization of 1,3-Enynes with Selenosulfonates in Water.

1,4-/1,3-Regioselective bifunctionalization of 1,3-enynes with selenosulfonates in water under catalyst-free conditions for the construction of sulfonyl allene and 1,3-disulfonyl-conjugated dienes respectively have been developed. The reactions feature mild reaction conditions in aqueous solution and remarkable regioselectivity controlled by substrates.

Study on Mudcake disintegration in clayey strata during shield tunneling: Effects of dispersants and bentonite slurry.

While tunnel boring machines (TBMs) tunneling in clayey strata, the adhered excavated soil on the cutterhead and cutting tools tends to form mudcake after compaction and consolidation. Mudcake can obstruct the cutterhead openings and rendering the cutting tools ineffective, leads to a substantial reduction in advance rate. Dispersants are recognized as an effective method for the disintegration of mudcakes. A novel set of equipment, comprising a mudcake compression device and a mudcake disintegration apparatus, is developed for assessing mudcake disintegration properties. The results showed that mudcakes underwent a tripartite disintegration process in water, including an initial stage, a rapid disintegration stage, and a stable stage. In the initial stage, the mudcakes absorbed water before disintegration, resulting in marginal changes in the weight of the disintegrated mudcakes. In the rapid disintegration stage, the weight of the disintegrated mudcakes increased quickly. During the stable stage, the weight of the disintegrated mudcakes remained relatively constant. The submersion of mudcakes in a dispersant solution substantially increased the rate of disintegration. Greater dispersant concentration corresponded to an increase in the disintegration rate. No weight gain was observed in mudcakes during the initial disintegration stage. When mudcakes disintegrated in a bentonite slurry, the weight of the disintegrated mudcakes initially decreased and then stabilized. The weight of the disintegrated mudcakes turned negative, indicating an increase in the weight of mudcakes. This suggested that bentonite significantly hindered mudcake disintegration.

Study on the Mechanism of Action of the Traditional Chinese Medical Prescription Gushukang in Treating Osteoporosis Based on Network Pharmacology and Experimental Verification.

BACKGROUND: Gushukang (GSK), a traditional Chinese medical prescription, has made a great and extensive contribution to the treatment of different forms of osteoporosis, but polypharmacology studies of its mechanism of action are lacking. This study investigates the pharmacological mechanism of osteoporosis using network pharmacology and molecular docking. Experimental verification was carried out to confirm the efficacy of GSK on RANKLinduced osteoclast differentiation in RAW264.7 cells to verify the network pharmacology studies. METHODS: The effective chemical components and corresponding targets of osteoporosis with oral bioavailability of more than 30% and drug-like properties greater than 0.18 were searched in the TCMSP and TCM-ID databases. DrugBank, GeneCards, OMIM, TTD, and other databases were examined for targets related to osteoporosis. Using Cytoscape software, a network of possible TCM-active ingredient-osteoporosis targets was created. STRING software was used to create the networks of protein-protein interactions. The DAVID program was carried out to conduct GO and KEGG pathway enrichment analyses of the targets. Molecular docking and pattern of action analysis were carried out using software like AutoDock Vina and Discovery Studio Visualizer. The growth media for RAW264.7 cells contained varying doses of GSK serum and 50 ng/mL RANKL. The activity of TRAP was altered. Additionally, genes related to osteoclasts were examined using an RT-PCR assay. RESULTS: Network pharmacological analysis revealed that the primary efficacy targets of osteoporosis were PTGS2, PTGS1, HSP90AA1, NCOA2, ADRB2, ESR1, NCOA1, and AR. The pharmacological targets of osteoporosis may be mediated by substances including quercetin, kaempferol, luteolin, naringenin, icariin, anthocyanin, tanshinone IIA, and cryptotanshinone. GSK markedly inhibited RANKL-induced TRAP activity. qRT-PCR results revealed decreased expression of the PTGS2 and ADRB2 genes upon GSK treatment. CONCLUSION: The findings of network pharmacology, molecular docking, as well as experimental verification provide a new further study for elucidating the pharmacodynamic substance basis and polypharmacology mechanism of GSK in treating osteoporosis.

Characterizing the Dynamic Expression of C1q/TNF-α-Related Protein 6 (CTRP6) during Pregnancy in Humans and Mice with Gestational Diabetes Mellitus.

AIM: C1q/TNF-related protein 6 (CTRP6) is a novel adipokine involved in insulin resistance. Thus, we aim to investigate the expression profile of CTRP6 in the plasma, adipose tissue and placenta of GDM patients and mice. METHODS: Chinese Han pregnant women (GDM n = 9, control n = 10) with a scheduled caesarean section delivery were recruited. A number of high-fat diet (HFD) induced-pregnancy C57BL/6 mice were chosen as an animal model of GDM. Circulating levels of CTRP6 and adiponectin were examined by ELISA. CTRP6 expression in adipose tissue and placenta were detected by real-time qPCR and WB. RESULT: Plasma CTRP6 levels were decreased during the first and second trimesters in mice, as well as the second and third trimesters in patients, while they were increased at delivery in GDM patients and mice. Plasma CTRP6 levels were significantly correlated with WBC, systolic pressure, diastolic pressure and fasting blood glucose. Moreover, CTRP6 mRNA expression in the subcutaneous (sWAT) and omental white adipose tissue (oWAT), as well as in the placenta, was significantly higher in GDM human patients at cesarean delivery. Furthermore, the mRNA expression of Ctrp6 was increased in the sWAT and visceral WAT (vWAT), whilst decreased in the interscapular brown adipose tissue (iBAT), of GDM mice at cesarean delivery. CONCLUSION: Dynamically expressed CTRP6 may be served as a candidate target for treatment of GDM.