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1.
Sci Total Environ ; 947: 174703, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38997028

ABSTRACT

River deltas, such as the Ganges-Brahmaputra-Meghna (GBM) delta, are highly vulnerable to flooding, exacerbated by intense human activities and rapid urban growth. This study explores the evolution of urban flood risks in the GBM delta under the combined impacts of climate change and urban expansion. Unlike traditional assessments that focus on a single flood source, we consider multiple sources-coastal, fluvial, and pluvial. Our findings indicate that future urban expansion will significantly increase flood exposure, with a substantial rise in flood risk from all sources by the end of this century. Climate change is the main driver of increased coastal flood risks, while urban growth primarily amplifies fluvial, and pluvial flood risks. This highlights the urgent need for adaptive urban planning strategies to mitigate future flooding and support sustainable urban development. The extreme high emissions future scenario (SSP5-8.5) shows the largest urban growth and consequent flood risk, emphasizing the necessity for preemptive measures to mitigate future urban flooding. Our study provides crucial insights into flood risk dynamics in delta environments, aiding policymakers and planners in developing resilience strategies against escalating flood threats.

2.
Article in English | MEDLINE | ID: mdl-38973529

ABSTRACT

BACKGROUND: The objective of antiviral therapy for chronic viral hepatitis B infection (CHB) is to achieve a functional cure. An important viral marker in the serum of patients with CHB is the serum hepatitis B core-related antigen (HBcrAg). However, there is limited research on HBcrAg in juvenile patients with CHB. In this study, we aimed to investigate the correlation between serum HBcrAg and other hepatitis B virus (HBV) markers in children with CHB and its predictive significance for prognosis during antiviral therapy. METHODS: A single-center retrospective study was conducted involving 79 children with CHB, aged between 0 and 16 years. All the children were treated with interferon [or combined nucleos(t)ide analogs] for 48 weeks. HBcrAg, hepatitis B surface antigen (HBsAg), and HBV DNA were measured before treatment, and at 12 and 48 weeks after treatment. The enrolled children were classified into the seroclearance group and the nonseroclearance group based on the therapeutic outcome. RESULTS: HBsAg seroclearance was observed in 28 out of 79 patients and hepatitis B e antigen seroconversion without HBsAg seroclearance was observed in 14 out of 79 patients following the conclusion of the treatment, with baseline HBcrAg titer levels showing no statistical significance in both the seroclearance and nonseroclearance groups (P = 0.277). HBsAg and HBV DNA were positively correlated with HBcrAg in children with CHB (R2 = 0.3289, 0.4388). The area under the receiver operating characteristic curve of the decrease in HBcrAg at 12 weeks of treatment as a predictor of seroclearance at 48 weeks of treatment, exhibited a value of 0.77. CONCLUSION: A decrease in serum HBcrAg levels in children with hepatitis B serves as a prognostic indicator.

3.
J Control Release ; 373: 38-54, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38986909

ABSTRACT

Multiple oxaliplatin-resistance mechanisms have been proposed such as increase of anti-inflammatory M2 macrophages and lack of cytotoxic T-cells. Thereby oxaliplatin chemotherapy promotes an immunosuppressive tumor microenvironment and inhibits anti-tumor efficacy. It has been shown that toll-like receptor (TLR) agonists are capable of triggering broad inflammatory responses, which may potentially reduce oxaliplatin-resistance and improve the efficacy of chemotherapy. In this study, we established colorectal tumor-bearing zebrafish and mice, and investigated the effects of TLR agonists and oxaliplatin in macrophage function and anti-tumor T cell immunity as well as tumor growth control in vivo. To increase the potential of this strategy as well minimize side effects, neutral liposomes carrying oxaliplatin and cationic liposomes co-loaded with TLR agonists Poly I:C and R848 were employed for maximum immune activation. Both of two liposomal systems exhibited good physicochemical properties and excellent biological activities in vitro. The combination strategy delivered by liposomes showed more pronounced tumor regression and correlated with decreased M2 macrophage numbers in both zebrafish and mice. Increasing numbers of dendritic cells, DC maturation and T cell infiltration mediated via immunogenic cell death were observed in treated mice. Our study offers valuable insights into the potential of liposomal combination therapy to improve cancer treatment by reprogramming the tumor microenvironment and enhancing immune responses.

4.
World J Gastrointest Surg ; 16(6): 1791-1802, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38983329

ABSTRACT

BACKGROUND: Metastatic colorectal cancer (mCRC) is a common malignancy whose treatment has been a clinical challenge. Cancer-specific survival (CSS) plays a crucial role in assessing patient prognosis and treatment outcomes. However, there is still limited research on the factors affecting CSS in mCRC patients and their correlation. AIM: To predict CSS, we developed a new nomogram model and risk grading system to classify risk levels in patients with mCRC. METHODS: Data were extracted from the United States Surveillance, Epidemiology, and End Results database from 2018 to 2023. All eligible patients were randomly divided into a training cohort and a validation cohort. The Cox proportional hazards model was used to investigate the independent risk factors for CSS. A new nomogram model was developed to predict CSS and was evaluated through internal and external validation. RESULTS: A multivariate Cox proportional risk model was used to identify independent risk factors for CSS. Then, new CSS columns were developed based on these factors. The consistency index (C-index) of the histogram was 0.718 (95%CI: 0.712-0.725), and that of the validation cohort was 0.722 (95%CI: 0.711-0.732), indicating good discrimination ability and better performance than tumor-node-metastasis staging (C-index: 0.712-0.732). For the training set, 0.533, 95%CI: 0.525-0.540; for the verification set, 0.524, 95%CI: 0.513-0.535. The calibration map and clinical decision curve showed good agreement and good potential clinical validity. The risk grading system divided all patients into three groups, and the Kaplan-Meier curve showed good stratification and differentiation of CSS between different groups. The median CSS times in the low-risk, medium-risk, and high-risk groups were 36 months (95%CI: 34.987-37.013), 18 months (95%CI: 17.273-18.727), and 5 months (95%CI: 4.503-5.497), respectively. CONCLUSION: Our study developed a new nomogram model to predict CSS in patients with synchronous mCRC. In addition, the risk-grading system helps to accurately assess patient prognosis and guide treatment.

5.
J Biochem Mol Toxicol ; 38(8): e23780, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39056188

ABSTRACT

Sodium and potassium channels, especially Nav1.5 and Kir2.1, play key roles in the formation of action potentials in cardiomyocytes. These channels interact with, and are regulated by, synapse-associated protein 97 (SAP97). However, the regulatory role of SAP97 in myocyte remains incompletely understood. Here, we investigate the function of SAP97 phosphorylation in the regulation of Nav1.5 and Kir2.1 channel complexes and the upstream regulation of SAP97. We found that SAP97 is phosphorylated by casein kinase II (CK2) in vitro. In addition, transfection of casein kinase 2 interacting protein-1 (CKIP-1) into cardiomyocytes to drive CK2 from the nucleus to the cytoplasm, increased SAP97 phosphorylation and Nav1.5 and Kir2.1 current activity. These findings demonstrated that CKIP-1 modulates the subcellular translocation of CK2, which regulates Nav1.5 and Kir2.1 channel complex formation and activity in cardiomyocytes.


Subject(s)
Casein Kinase II , Myocytes, Cardiac , NAV1.5 Voltage-Gated Sodium Channel , Potassium Channels, Inwardly Rectifying , Myocytes, Cardiac/metabolism , Casein Kinase II/metabolism , Potassium Channels, Inwardly Rectifying/metabolism , Potassium Channels, Inwardly Rectifying/genetics , NAV1.5 Voltage-Gated Sodium Channel/metabolism , NAV1.5 Voltage-Gated Sodium Channel/genetics , Animals , Rats , Phosphorylation , Protein Transport , Humans , Carrier Proteins/metabolism , Rats, Sprague-Dawley
6.
Food Chem ; 457: 139807, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38964207

ABSTRACT

This study was conducted to comprehensively characterize, metabolites, lipids, and volatile flavor compounds of NingXiang (NX) pigs, Berkshire (BKS) pigs, and their crossbred (Berkshire × Ningxiang, BN) pigs using multi-omics technique. The results showed that NX had high intramuscular fat (IMF) content and meat redness. The metabolite and lipid compositions were varied greatly among three pig breeds. The NX pigs exhibited distinctive sweet, fruity, and floral aroma while BN pigs have inherited this flavor profile. 2-pentylfuran, pentanal, 2-(E)-octenal, and acetic acid were the key volatile flavor compounds (VOC) of NX and BKS pork. The VOCs were influenced by the composition and content of metabolites and lipids. The NX pigs have excellent meat quality traits, unique flavor profiles, and high degree of genetic stability regarding flavor. The study deepens our understanding of the flavor of Chinese indigenous pigs, providing theoretical basis to understand the meat flavor regulation under different feeding conditions.

7.
Front Neurosci ; 18: 1395671, 2024.
Article in English | MEDLINE | ID: mdl-38952922

ABSTRACT

Evidence has demonstrated that exoskeleton robots can improve intestinal function in patients with spinal cord injury (SCI). However, the underlying mechanisms remain unelucidated. This study investigated the effects of exoskeleton-assisted walking (EAW) on intestinal function and intestinal flora structure in T2-L1 motor complete paraplegia patients. The results showed that five participants in the EAW group and three in the conventional group reported improvements in at least one bowel management index, including an increased frequency of bowel evacuations, less time spent on bowel management per day, and less external assistance (manual digital stimulation, medication, and enema usage). After 8 weeks of training, the amount of glycerol used in the EAW group decreased significantly (p <0.05). The EAW group showed an increasing trend in the neurogenic bowel dysfunction (NBD) score after 8 weeks of training, while the conventional group showed a worsening trend. Patients who received the EAW intervention exhibited a decreased abundance of Bacteroidetes and Verrucomicrobia, while Firmicutes, Proteobacteria, and Actinobacteria were upregulated. In addition, there were decreases in the abundances of Bacteroides, Prevotella, Parabacteroides, Akkermansia, Blautia, Ruminococcus 2, and Megamonas. In contrast, Ruminococcus 1, Ruminococcaceae UCG002, Faecalibacterium, Dialister, Ralstonia, Escherichia-Shigella, and Bifidobacterium showed upregulation among the top 15 genera. The abundance of Ralstonia was significantly higher in the EAW group than in the conventional group, and Dialister increased significantly in EAW individuals at 8 weeks. This study suggests that EAW can improve intestinal function of SCI patients in a limited way, and may be associated with changes in the abundance of intestinal flora, especially an increase in beneficial bacteria. In the future, we need to further understand the changes in microbial groups caused by EAW training and all related impact mechanisms, especially intestinal flora metabolites. Clinical trial registration: https://www.chictr.org.cn/.

8.
Sci Total Environ ; 946: 174057, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-38914340

ABSTRACT

Root-associated microbiota provide great fitness to hosts under environmental stress. However, the underlying microecological mechanisms controlling the interaction between heavy metal-stressed plants and the microbiota are poorly understood. In this study, we screened and isolated representative amplicon sequence variants (strain M4) from rhizosphere soil samples of Trifolium repens L. growing in areas with high concentrations of heavy metals. To investigate the microecological mechanisms by which T. repens adapts to heavy metal stress in abandoned mining areas, we conducted potting experiments, bacterial growth promotion experiments, biofilm formation experiments, and chemotaxis experiments. The results showed that high concentrations of heavy metals significantly altered the rhizosphere bacterial community structure of T. repens and significantly enriched Microbacterium sp. Strain M4 was demonstrated to significantly increased the biomass and root length of T. repens under heavy metal stress. Additionally, L-proline and stigmasterol could promote bacterial growth and biofilm formation and induce chemotaxis for strain M4, suggesting that they are key rhizosphere secretions of T. repens for Microbacterium sp. recruitment. Our results suggested that T. repens adapted the heavy metal stress by reshaping rhizosphere secretions to modify the rhizosphere microbiota.


Subject(s)
Metals, Heavy , Microbacterium , Mining , Plant Roots , Rhizosphere , Soil Microbiology , Soil Pollutants , Trifolium , Trifolium/microbiology , Soil Pollutants/toxicity , Plant Roots/microbiology , Microbacterium/physiology , Microbiota/drug effects , Lead/toxicity , Zinc
9.
J Pharmacol Exp Ther ; 390(2): 240-249, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-38902033

ABSTRACT

Sympathetic hyperinnervation is the leading cause of fatal ventricular arrhythmia (VA) after myocardial infarction (MI). Cardiac mast cells cause arrhythmias directly through degranulation. However, the role and mechanism of mast cell degranulation in sympathetic remodeling remain unknown. We investigated the role of oxytocin (OT) in stabilizing cardiac mast cells and improving sympathetic innervation in rats. MI was induced by coronary artery ligation. Western blotting, immunofluorescence, and toluidine staining of mast cells were performed to determine the expression and location of target protein. Mast cells accumulated significantly in peri-infarcted tissues and were present in a degranulated state. They expressed OT receptor (OTR), and OT infusion reduced the number of degranulated cardiac mast cells post-MI. Sympathetic hyperinnervation was attenuated as assessed by immunofluorescence for tyrosine hydroxylase (TH). Seven days post-MI, the arrhythmia score of programmed electrical stimulation was higher in vehicle-treated rats with MI than in rats treated with OT. An in vitro study showed that OT stabilized mast cells via the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Further in vivo studies on OTR-deficient mice showed worsening mast cell degranulation and worsening sympathetic innervation. OT pretreatment inhibited cardiac mast cell degranulation post-MI and prevented sympathetic hyperinnervation, along with mast cell stabilization via the PI3K/Akt pathway. SIGNIFICANCE STATEMENT: This is the first study to elucidate the role and mechanism of oxytocin (OT) in inflammatory-sympathetic communication mediated sympathetic hyperinnervation after myocardial infarction (MI), providing new approaches to prevent fatal arrhythmias.


Subject(s)
Cell Degranulation , Mast Cells , Myocardial Infarction , Oxytocin , Rats, Sprague-Dawley , Receptors, Oxytocin , Sympathetic Nervous System , Animals , Oxytocin/pharmacology , Oxytocin/metabolism , Myocardial Infarction/drug therapy , Myocardial Infarction/metabolism , Mast Cells/drug effects , Mast Cells/metabolism , Rats , Sympathetic Nervous System/drug effects , Sympathetic Nervous System/metabolism , Male , Cell Degranulation/drug effects , Receptors, Oxytocin/metabolism , Receptors, Oxytocin/antagonists & inhibitors , Mice , Signal Transduction/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Arrhythmias, Cardiac/metabolism , Arrhythmias, Cardiac/drug therapy , Arrhythmias, Cardiac/etiology
10.
Angiogenesis ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38842752

ABSTRACT

Conjunctival melanoma (CoM) is a rare but potentially lethal cancer of the eye, with limited therapeutic option for metastases. A better understanding how primary CoM disseminate to form metastases is urgently needed in order to develop novel therapies. Previous studies indicated that primary CoM tumors express Vascular Endothelial Growth Factor (VEGF) and may recruit pro-tumorigenic M2-like macrophages. However, due to a lack of proper models, the expected role of angiogenesis in the metastatic dissemination of CoM is still unknown. We show that cells derived from two CoM cell lines induce a strong angiogenic response when xenografted in zebrafish larvae. CoM cells are highly glycolytic and secrete lactate, which recruits and polarizes human and zebrafish macrophages towards a M2-like phenotype. These macrophages elevate the levels of proangiogenic factors such as VEGF, TGF-ß, and IL-10 in the tumor microenvironment to induce an angiogenic response towards the engrafted CoM cells in vivo. Chemical ablation of zebrafish macrophages or inhibition of glycolysis in CoM cells terminates this response, suggesting that attraction of lactate-dependent macrophages into engrafted CoM cells drives angiogenesis and serves as a possible dissemination mechanism for glycolytic CoM cells.

11.
J Exp Clin Cancer Res ; 43(1): 154, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822363

ABSTRACT

BACKGROUND: RNA modifications of transfer RNAs (tRNAs) are critical for tRNA function. Growing evidence has revealed that tRNA modifications are related to various disease processes, including malignant tumors. However, the biological functions of methyltransferase-like 1 (METTL1)-regulated m7G tRNA modifications in breast cancer (BC) remain largely obscure. METHODS: The biological role of METTL1 in BC progression were examined by cellular loss- and gain-of-function tests and xenograft models both in vitro and in vivo. To investigate the change of m7G tRNA modification and mRNA translation efficiency in BC, m7G-methylated tRNA immunoprecipitation sequencing (m7G tRNA MeRIP-seq), Ribosome profiling sequencing (Ribo-seq), and polysome-associated mRNA sequencing were performed. Rescue assays were conducted to decipher the underlying molecular mechanisms. RESULTS: The tRNA m7G methyltransferase complex components METTL1 and WD repeat domain 4 (WDR4) were down-regulated in BC tissues at both the mRNA and protein levels. Functionally, METTL1 inhibited BC cell proliferation, and cell cycle progression, relying on its enzymatic activity. Mechanistically, METTL1 increased m7G levels of 19 tRNAs to modulate the translation of growth arrest and DNA damage 45 alpha (GADD45A) and retinoblastoma protein 1 (RB1) in a codon-dependent manner associated with m7G. Furthermore, in vivo experiments showed that overexpression of METTL1 enhanced the anti-tumor effectiveness of abemaciclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor. CONCLUSION: Our study uncovered the crucial tumor-suppressive role of METTL1-mediated tRNA m7G modification in BC by promoting the translation of GADD45A and RB1 mRNAs, selectively blocking the G2/M phase of the cell cycle. These findings also provided a promising strategy for improving the therapeutic benefits of CDK4/6 inhibitors in the treatment of BC patients.


Subject(s)
Breast Neoplasms , Methyltransferases , RNA, Transfer , Humans , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Female , Mice , Animals , Methyltransferases/metabolism , Methyltransferases/genetics , RNA, Transfer/genetics , RNA, Transfer/metabolism , Methylation , Cell Line, Tumor , Cell Proliferation , Carcinogenesis/genetics , Cell Cycle Checkpoints , Protein Biosynthesis , Xenograft Model Antitumor Assays , Mice, Nude
12.
Micromachines (Basel) ; 15(6)2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38930757

ABSTRACT

Laser-based additive manufacturing (LAM) represents one of the most forward-thinking transformations in how we conceive, design, and bring to life engineered solutions [...].

13.
Animals (Basel) ; 14(12)2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38929420

ABSTRACT

Lactobacillus delbrueckii intervention can regulate body lipid metabolism, but the underlying mechanism remains unclear. Our study investigated the effects of L. delbrueckii on serum lipid levels, tissular fat metabolism and deposition, bile acid metabolism, and gut microbiota in Ningxiang pigs. Ninety-six pigs were divided into two groups and fed basal diets containing either 0 (CON) or 0.1% L. delbrueckii (LD) for 60 days. Dietary L. delbrueckii promoted fecal total bile acid (TBA) excretion and increased hepatic enzyme activities related to cholesterol and bile synthesis but decreased hepatic and serum lipid concentrations. L. delbrueckii downregulated gene expression associated with fatty acid synthesis but upregulated gene expression related to lipolysis and ß-fatty acid oxidation in liver and subcutaneous fat. L. delbrueckii elevated gut Lactobacillus abundance and colonic short-chain fatty acid (SCFA)-producing bacteria but declined the abundance of some pathogenic bacteria. These findings demonstrated that L. delbrueckii modulated intestinal microbiota composition and facilitated fecal TBA excretion to regulate hepatic fat metabolism, which resulted in less lipid deposition in the liver and reduced levels of serum lipids.

14.
Open Med (Wars) ; 19(1): 20240975, 2024.
Article in English | MEDLINE | ID: mdl-38883335

ABSTRACT

Objective: Sympathetic hyperinnervation following myocardial infarction (MI) is one of the primary causes of ventricular arrhythmias (VAs) after MI. Nerve growth factor (NGF) is a key molecule that induces sympathetic nerve remodeling. Previous studies have confirmed that microRNA (miR)-let-7a interacts with NGF. However, whether miR-let-7a is involved in sympathetic remodeling after MI remains unknown. We aimed to investigate whether miR-let-7a was associated with the occurrence of VA after MI. Methods and results: A rat model of myocardial infarction was established using left coronary artery ligation. miR-let-7a expression levels were analyzed by reverse transcription-quantitative PCR. Western blotting was also used to examine NGF expression levels in vivo and in M1 macrophages in vitro. The relationship between miR-let-7a and NGF levels was investigated using a luciferase reporter assay. The results revealed that the expression of miR-let-7a decreased significantly after MI, while NGF expression was significantly upregulated. In addition, overexpression of miR-let-7a effectively inhibited NGF expression in rats, which was also verified in M1 macrophages. Tyrosine hydroxylase and growth-associated protein 43 immunofluorescence results revealed that the administration of a miR-let-7a overexpression lentivirus to rats inhibited sympathetic remodeling after MI. Programmed electrical stimulation, renal sympathetic nerve activity recording, and heart rate variability measurements showed that miR-let-7a overexpression decreased sympathetic activity. Conclusions: These findings provide novel insights into the molecular mechanisms by which miR-let-7a and NGF contribute to the progression of sympathetic nerve remodeling after MI. Therefore, miR-let-7a may be a promising therapeutic target to reduce the incidence of arrhythmia following MI.

15.
Lancet Haematol ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38885672

ABSTRACT

BACKGROUND: Sovleplenib, a novel spleen tyrosine kinase (SYK) inhibitor, showed promising safety and activity in patients with primary immune thrombocytopenia in a phase 1b/2 trial. We aimed to evaluate the efficacy and safety of sovleplenib in patients with chronic primary immune thrombocytopenia. METHODS: This randomised, double-blind, placebo-controlled, phase 3 trial (ESLIM-01) was done in 34 clinical centres in China. Eligible patients, aged 18-75 years, had chronic primary immune thrombocytopenia, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and received one or more previous treatments. Patients were randomly assigned (2:1) to receive oral sovleplenib or placebo, 300 mg once daily, for 24 weeks. Randomisation was stratified by baseline platelet counts, previous splenectomy, and concomitant treatment for anti-immune thrombocytopenia at baseline. The primary endpoint was durable response rate (proportion of patients with a platelet count of ≥50 × 109/L on at least four of six scheduled visits between weeks 14 and 24, not affected by rescue treatment) assessed by intention-to-treat. The trial is registered with ClinicalTrials.gov, NCT05029635, and the extension, open-label phase is ongoing. FINDINGS: Between Sept 29, 2021, and Dec 31, 2022, 188 patients were randomly assigned to receive sovleplenib (n=126) or placebo (n=62). 124 (66%) were female, 64 (34%) were male, and all were of Asian ethnicity. Median previous lines of immune thrombocytopenia therapy were 4·0, and 134 (71%) of 188 patients had received previous thrombopoietin or thrombopoietin receptor agonist. The primary endpoint was met; durable response rate was 48% (61/126) with sovleplenib compared with zero with placebo (difference 48% [95% CI 40-57]; p<0·0001). The median time to response was 8 days with sovleplenib compared with 30 days with placebo. 125 (99%) of 126 patients in the sovleplenib group and 53 (85%) of 62 in the placebo group reported treatment-emergent adverse events (TEAEs), and most events were mild or moderate. Frequent TEAEs of grade 3 or higher for sovleplenib versus placebo were platelet count decreased (7% [9/126] vs 10% [6/62]), neutrophil count decreased (3% [4/126] vs 0% [0/62]), and hypertension (3% [4/126] vs 0% [0/62]). Incidences of serious TEAEs were 21% (26/126) in the sovleplenib group and 18% (11/62) in the placebo group. There were no deaths in the study. INTERPRETATION: Sovleplenib showed a clinically meaningful sustained platelet response in patients with chronic primary immune thrombocytopenia, with a tolerable safety profile and improvement in quality of life. Sovleplenib could be a potential treatment option for patients with immune thrombocytopenia who received one or more previous therapy. FUNDING: HUTCHMED and Science and Technology Commission of Shanghai Municipality.

16.
Sci Adv ; 10(26): eado6476, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38924402

ABSTRACT

Mechanical computing encodes information in deformed states of mechanical systems, such as multistable structures. However, achieving stable mechanical memory in most multistable systems remains challenging and often limited to binary information. Here, we report leveraging coupling kinematic bifurcation in rigid cube-based mechanisms with elasticity to create transformable, multistable mechanical computing metastructures with stable, high-density mechanical memory. Simply stretching the planar metastructure forms a multistable corrugated platform. It allows for independent mechanical or magnetic actuation of individual bistable element, serving as pop-up voxels for display or binary units for various tasks such as information writing, erasing, reading, encryption, and mechanologic computing. Releasing the pre-stretched strain stabilizes the prescribed information, resistant to external mechanical or magnetic perturbations, whereas re-stretching enables editable mechanical memory, akin to selective zones or disk formatting for information erasure and rewriting. Moreover, the platform can be reprogrammed and transformed into a multilayer configuration to achieve high-density memory.

17.
Front Microbiol ; 15: 1367877, 2024.
Article in English | MEDLINE | ID: mdl-38933026

ABSTRACT

Introduction: This study was conducted to evaluate the effects of dietary galacto-oligosaccharides (GOS) and hyocholic acids (HCA) during late gestation and lactation on reproductive performance, colostrum quality, antioxidant capacity and gut microbiota in multiparous sows. Methods: A total of 60 healthy multiparous cross-bred sows (Landrace × Yorkshire) were randomly fed 4 groups diets as follows: the basal diets (CTRL group), or the basal diets containing only 600 mg/kg GOS (GOS group), 600 mg/kg GOS + 100 mg/kg HCA (GOS + Low HCA group), and 600 mg/kg + 200 mg/kg HCA (GOS + High HCA group) from d 85 of gestation to weaning. Multiple parameters of sows were determined. Results: There was a trend of shortening the labor process of sows (p = 0.07) in the GOS group and GOS + Low/High HCA group. Compared with the CTRL group, the GOS + Low/High HCA group increased the average piglets weight at birth (p < 0.05), and increased the IgA concentration of colostrum (p < 0.05). In addition, serum triglyceride (TG) concentration was lower (p < 0.05), and serum total antioxidant capacity (T-AOC) was higher (p < 0.05) in the GOS and GOS + Low/High HCA groups than in the CTRL group at farrowing. Serum catalase (CAT) activities was higher in the GOS and GOS + High HCA groups than in the CTRL group at farrowing. The 16S rRNA analysis showed that GOS combination with high-dose HCA shaped the composition of gut microbiota in different reproductive stages (d 107 of gestation, G107; d 0 of lactation, L0; d 7 of lactation, L7). At the phylum level, the relative abundance of Bacteroidota and Desulfobacterota in G107, Bacteroidota, and Proteobacteria in L0, and Planctomycetota in L7 was increased in GOS + High HCA group (p < 0.05). Spearman correlation analysis showed that Streptococcus was positively correlated with the serum TG but negatively correlated with the average piglets weight at birth (p < 0.05). Conclusion: This investigation demonstrated that the administration of galacto-oligosaccharides (GOS) in conjunction with hyocholic acids (HCA), to sows with nutrient restrictions during late gestation and lactation, further improved their antioxidant capacity and milk quality. The observed beneficial effects of GOS + HCA supplementation could potentially be linked to an improvement in gut microbiota disorders of the sows.

18.
Ann Surg Open ; 5(2): e437, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38911648

ABSTRACT

Objective: To determine whether socio-demographic and preoperative clinical factors contribute to the percent total body weight loss (%TBWL) after bariatric surgery (BS). Background: BS is the most effective long-term treatment for medically complicated obesity. More information is needed about the factors that contribute to postoperative %TBWL in large and ethnically diverse cohorts. Methods: This retrospective study conducted in the Kaiser Permanente Northern California region included 7698 patients who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) between January 2009 and March 2015. Trajectory analyses were conducted from 5-year follow-up data to assign patients to "low," "average," or "high" postoperative %TBWL groups. We then evaluated whether age, sex, race/ethnicity, neighborhood deprivation index and preoperative body mass index (BMI)/weight loss, diabetes, hypertension, and sleep apnea contributed to postoperative %TBWL using logistic regression models. Results: Of 7698 patients (83.2% women), 48.6% underwent a RYGB and 51.4% underwent a SG. Postoperative %TBWL trajectories over 5 years were obtained in 6229 (81%) of 7698 eligible patients. About 27.8% and 29.3% of patients followed the "low" postoperative %TBWL trajectory, for RYGB and SG, respectively. Men, older patients, and Asian, Black, and Hispanic/Latino patients were more likely to be classified in the low postoperative %TBWL group. Patients showing lower postoperative %TBWL had a lower preoperative BMI (but lost less weight before surgery) and were more likely to have preoperative comorbidities. Conclusions: This study confirms and extends prior findings of the effects of several demographic and preoperative clinical factors on postoperative weight loss. Findings could improve the support of patients to achieve desired surgical outcomes.

20.
Article in English | MEDLINE | ID: mdl-38940790

ABSTRACT

Background: Trigeminal neuralgia (TN), characterized by severe facial pain, warrants effective perioperative care. There is a critical need for evidence-based perioperative nursing interventions to enhance outcomes and well-being in patients undergoing microballoon compression for trigeminal neuralgia. Objective: This study aims to investigate the impact of standardized nursing during the perioperative period of microballoon compression in patients with trigeminal neuralgia (TN). Methods: A total of 22 TN patients admitted to our hospital from December 2021 to December 2022 underwent microballoon compression treatment. The control group (CG) received standard neurosurgical routine nursing, while the observation group (OG) received standardized nursing during the perioperative period. Comparative analysis included assessments of pain intensity, psychological status, sleep quality, overall quality of life, incidence of complications, and patient satisfaction. Results: Following nursing interventions, both groups exhibited a decrease in scores on the Neuropathic Pain Scale (NPS), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), and Pittsburgh Sleep Quality Index (PSQI). The OG demonstrated significantly lower scores compared to the CG (P < .05). Post-nursing, SF-36 scores decreased in both groups, with the OG displaying lower scores than the CG (P < .05). Although complications were less frequent in the OG, and patient satisfaction was higher, these differences were not statistically significant (P > .05). Conclusions: The implementation of standardized nursing during the perioperative period of microballoon compression in TN patients resulted in reduced pain intensity, improved psychological well-being, enhanced sleep quality, and better overall quality of life. These findings suggest the intervention's potential for valuable clinical application and merit further promotion.

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