Early-life milk replacer feeding mediates lipid metabolism disorders induced by colonic microbiota and bile acid profiles to reduce body weight in goat model.

BACKGROUND: Dysregulation of lipid metabolism and its consequences on growth performance in young ruminants have attracted attention, especially in the context of alternative feeding strategies. This study aims to elucidate the effects of milk replacer (MR) feeding on growth, lipid metabolism, colonic epithelial gene expression, colonic microbiota composition and systemic metabolism in goat kids compared to breast milk (BM) feeding, addressing a critical knowledge gap in early life nutrition. METHODS: Ten female goat kids were divided into 2 groups: those fed breast milk (BM group) and those fed a milk replacer (MR group). Over a period of 28 d, body weight was monitored and blood and tissue samples were collected for biochemical, transcriptomic and metabolomic analyses. Profiling of the colonial microbiota was performed using 16S rRNA gene sequencing. Intestinal microbiota transplantation (IMT) experiments in gnotobiotic mice were performed to validate causality. RESULTS: MR-fed pups exhibited reduced daily body-weight gain due to impaired lipid metabolism as evidenced by lower serum and liver total cholesterol (TC) and non-esterified fatty acid (NEFA) concentrations. Transcriptomic analysis of the colonic epithelium revealed upregulated genes involved in negative regulation of lipid metabolism, concomitant with microbiota shifts characterized by a decrease in Firmicutes and an increase in Actinobacteria. Specifically, genera such as Bifidobacterium and Prevotella were enriched in the MR group, while Clostridium and Faecalibacterium were depleted. Metabolomics analyses confirmed alterations in bile acid and fatty acid metabolic pathways. IMT experiments in mice recapitulated the metabolic phenotype observed in MR-fed goats, confirming the role of the microbiota in modulating host lipid metabolism. CONCLUSIONS: Milk replacer feeding in goat kids disrupts lipid metabolism and gut microbiota dynamics, resulting in reduced growth rates and metabolic alterations. These findings highlight the importance of early nutritional intervention on metabolic programming and suggest that modulation of the gut microbiota may be a target for improving growth and metabolic health in ruminants. This study contributes to the understanding of nutritional management strategies in livestock and their impact on animal health and productivity.

Is there a duration-characteristic relationship for trypsin exposure on tendon? A study on anterior cruciate ligament reconstruction in a rabbit model.

Background: Decellularized allograft tendons are highly regarded for their accessibility and the reduced risk of immune rejection, making them a promising choice for grafting due to their favorable characteristics. However, effectively integrating reconstructed tendons with host bone remains a significant clinical challenge. Purpose: This study aims to investigate the relationship between the duration of tendon exposure to trypsin and its impact on tendon biomechanical properties and healing capacity. Methods: Morphological assessments and biochemical quantifications were conducted. Allograft tendons underwent heterotopic transplantation into the anterior cruciate ligament (ACL) in a rabbit model, with specimens harvested 6 weeks post-surgery for a comparative analysis of cell adhesion strength and mechanical performance. Duration-response curves were constructed using maximum stress and cell adhesion quantity as primary indicators. Results: The trypsin treatment enhanced cell adhesion on the tendon surface. Adhesion rates in the control group vs. the experimental groups were as follows: 3.10 ± 0.56% vs. 4.59 ± 1.51%, 5.36 ± 1.24%, 6.12 ± 1.98%, and 8.27 ± 2.34% (F = 6.755, p = 0.001). However, increasing treatment duration led to a decline in mechanical properties, with the ultimate load (N) in the control vs. experimental groups reported as 103.30 ± 10.51 vs. 99.59 ± 4.37, 93.15 ± 12.38, 90.42 ± 7.87, and 82.68 ± 6.89, F = 4.125 (p = 0.013). Conclusion: The findings reveal an increasing trend in adhesion effectiveness with prolonged exposure duration, while mechanical strength declines. The selection of the optimal processing duration should involve careful consideration of the benefits derived from both outcomes.

Discovery of SILA-123 as a Highly Potent FLT3 Inhibitor for the Treatment of Acute Myeloid Leukemia with Various FLT3 Mutations.

The FLT3-ITD (internal tandem duplication) mutant has been a promising target for acute myeloid leukemia (AML) drug discovery but is now facing the challenge of resistance due to point mutations. Herein, we have discovered a type II FLT3 inhibitor, SILA-123. This inhibitor has shown highly potent inhibitory effects against FLT3-WT (IC50 = 2.1 nM) and FLT3-ITD (IC50 = 1.0 nM), tumor cells with the FLT3-ITD mutant such as MOLM-13 (IC50 = 0.98 nM) and MV4-11 (IC50 = 0.19 nM), as well as BaF3 cells associated with the FLT3-ITD mutant and point mutations like BaF3-FLT3-ITD-G697R (IC50 = 3.0 nM). Moreover, SILA-123 exhibited promising kinome selectivity against 310 kinases (S score (10) = 0.06). In in vivo studies, SILA-123 significantly suppressed the tumor growth in MV4-11 (50 mg/kg/d, TGI = 87.3%) and BaF3-FLT3-ITD-G697R (50 mg/kg/d, TGI = 60.0%) cell-inoculated allograft models. Our data suggested that SILA-123 might be a promising drug candidate for FLT3-ITD-positive AML.

The Effect of Opioid-Free Anesthesia with Transversus Abdominis Plane Block on Patients Undergoing Laparoscopic Sleeve Gastrectomy: Randomized Controlled Study.

Purpose: Anesthesia for metabolic-bariatric surgery is challenging due to the increased risk of opioid-related adverse events. The purpose of the investigation was to assess the feasibility and efficacy of multimodal opioid-free general anesthesia with transversus abdominis plane (TAP) block for laparoscopic sleeve gastrectomy in contrast with conventional opioid-based general anesthesia. Patients and Methods: Eighty patients who underwent laparoscopic sleeve gastrectomy and eventually 71 patients included in the analysis. They were randomly divided into an opioid-based anesthesia group (control group) with sufentanil or opioid-free anesthesia (OFA) group. Esketamine, dexmedetomidine, and TAP were as part of the OFA. Sevoflurane, dexamethasone, and muscle relaxants were administered intraoperatively to all patients. The primary outcome was antiemetic rescue within 24 hours after surgery. The secondary outcomes included pain scores, analgesic needs, extubation time, complications, the hemodynamic changes, and duration of hospital stay. Results: In contrast with the control group, the need for antiemetic rescue was significantly reduced (p= 0.035). Furthermore, the visual Analog Scale (VAS) for postoperative pain was considerably lower in the OFA group (p <0.01) than it was in the control group. There was no significant difference in the need for analgesic rescue in both groups (p= 0.155). Extubation time and post-anesthesia care unit (PACU) stay duration were equal between the two groups (p =0.328 and p =0.54). At the end of the surgery and after extubation, hemodynamic changes was more pronounced in the OFA group (p =0.027) than the control group. The length of the hospital stay was significantly shorter compared with the control group (p =0.002). Conclusion: OFA with TAP results in a significant decrease in the need for antiemetic rescue, a lower level of pain after the surgery, and a shorter hospital stay in contrast with anesthesia based on opioids.

Disease burden of AIDS in last 30-year period and its predicted level in next 25-years based on the global burden disease 2019.

BACKGROUND: This study examines global trends in acquired immune deficiency syndrome (AIDS) incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2019, focusing on regional disparities in AIDS incidence, mortality, and DALYs across various levels of socio-demographic index (SDI). It also investigates variations in AIDS incidence, mortality, and DALYs across different age groups, and projects specific trends for the next 25 years. METHODS: Comprehensive data on AIDS from 1990 to 2019 in 204 countries and territories was obtained from a GBD study. This included information on AIDS incidence, mortality, DALYs, and age-standardized rates (ASRs). Projections for AIDS incidence and mortality over the next 25 years were generated using the Bayesian age-period-cohort model. RESULTS: From 1990 to 2019, the global incidence of HIV cases increased from 1,989,282 to 2,057,710, while the age-standardized incidence rate (ASIR) decreased from 37.59 to 25.24 with an estimated annual percentage change (EAPC) of -2.38. The ASIR exhibited an upward trend in high SDI and high-middle SDI regions, a stable trend in middle SDI regions, and a downward trend in low-middle SDI and low SDI regions. In regions with higher SDI, the ASIR was higher in males than in females, while the opposite was observed in lower SDI regions. Throughout 1990 to 2019, the age-standardized death rate (ASDR) and age-standardized DALY rate remained stable, with EAPCs of 0.24 and 0.08 respectively. Countries with the highest HIV burden affecting women and children under five years of age are primarily situated in lower SDI regions, particularly in sub-Saharan Africa. Projections indicate a significant continued decline in the age-standardized incidence and mortality rates of AIDS over the next 25 years, for both overall and by gender. CONCLUSIONS: The global ASIR decreased from 1990 to 2019. Higher incidence and death rates were observed in the lower SDI region, indicating a greater susceptibility to AIDS among women and < 15 years old. This underscores the urgent need for increased resources to combat AIDS in this region, with focused attention on protecting women and < 15 years old as priority groups. The AIDS epidemic remained severe in sub-Saharan Africa. Projections for the next 25 years indicate a substantial and ongoing decline in both age-standardized incidence and mortality rates.

Unraveling Herpes Zoster Vaccine Hesitancy, Acceptance, and Its Predictors: Insights From a Scoping Review.

Objectives: Herpes zoster vaccination is critical in preventing herpes zoster virus infection and its associated consequences. Despite its relevance, global herpes zoster immunisation coverage remains alarmingly low. Understanding the factors that drive vaccine scepticism and acceptance is crucial for increasing immunisation rates and improving public health outcomes. Methods: This scoping review, following Joanna Briggs Institute guidelines, included 18 studies examining vaccine hesitancy, acceptance, and associated factors. Meticulous data analysis revealed hesitancy's intricate dynamics across countries and demographics. Results: Studies displayed a wide range of acceptance rates (2.8%-89.02%), showcasing the complex interplay of attitudes and behaviors towards vaccination. Reasons for vaccine refusal were repeatedly identified in this setting, including worries about potential adverse effects, views of vaccine necessity, and vaccine supply constraints. Notably, individuals' patterns of vaccine acceptance and hesitancy differed among countries, vaccines, and vaccination-related factors. Conclusion: Addressing acceptance hurdles by improving accessibility, providing accurate information, and strengthening healthcare recommendations is crucial. Understanding the multifaceted factors influencing hesitancy allows for targeted interventions, elevating immunization rates and enhancing public health globally.

KCNE4 is a crucial host factor for Orf virus infection by mediating viral entry.

The orf virus (ORFV) poses a serious threat to the health of domestic small ruminants (i.e., sheep and goats) and humans on a global scale, causing around $150 million in annual losses to livestock industry. However, the host factors involved in ORFV infection and replication are still elusive. In this study, we compared the RNA-seq profiles of ORFV-infected or non-infected sheep testicular interstitial cells (STICs) and identified a novel host gene, potassium voltage-gated channel subfamily E member 4 (KCNE4), as a key host factor involved in the ORFV infection. Both RNA-seq data and RT-qPCR assay revealed a significant increase in the expression of KCNE4 in the infected STICs from 9 to 48 h post infection (hpi). On the other hand, the RT-qPCR assay detected a decrease in ORFV copy number in both the STICs transfected by KCNE4 siRNA and the KCNE4 knockout (KO) HeLa cells after the ORFV infection, together with a reduced fluorescence ratio of ORFV-GFP in the KO HeLa cells at 24 hpi, indicating KCNE4 to be critical for the ORFV infection. Furthermore, the attachment and internalization assays showed decreased ORFV attachment, internalization, replication, and release by the KO HeLa cells, demonstrating a potential inhibition of ORFV entry into the cells by KCNE4. Pretreatment with the KCNE4 inhibitors such as quinidine and fluoxetine significantly repressed the ORFV infection. All our findings reveal KCNE4 as a novel host regulator of the ORFV entry and replication, shedding new insight into the interactive mechanism of ORFV infection. The study also highlights the K+ channels as possible druggable targets to impede viral infection and disease.

Unveiling the spatial distribution and transboundary pathways of FMD serotype O in Western China and its bordering countries.

Foot-and-mouth disease (FMD) is a severe, highly contagious viral disease of livestock that has a significant economic impact on domestic animals and threatens wildlife survival in China and border countries. However, effective surveillance and prevention of this disease is often incomplete and unattainable due to the cost, the great diversity of wildlife hosts, the changing range and dynamics, and the diversity of FMDV. In this study, we used predictive models to reveal the spread and risk of FMD in anticipation of identifying key nodes to control its spread. For the first time, the spatial distribution of FMD serotype O was predicted in western China and border countries using a niche model, which is a combination of eco-geographic, human, topographic, and vegetation variables. The transboundary least-cost pathways (LCPs) model for ungulates in the study area were also calculated. Our study indicates that FMD serotype O survival is seasonal at low altitudes (March and June) and more sensitive to temperature differences at high altitudes. FMD serotype O risk was higher in Central Asian countries and both were highly correlated with the population variables. Ten LCPs were obtained representing Pakistan, Kazakhstan, Kyrgyzstan, and China.

Multi-omic Analyses Shed Light on The Genetic Control of High-altitude Adaptation in Sheep.

Sheep were domesticated in the Fertile Crescent and then spread globally, where they have been encountering various environmental conditions. The Tibetan sheep has adapted to high altitudes on the Qinghai-Tibet Plateau over the past 3000 years. To explore genomic variants associated with high-altitude adaptation in Tibetan sheep, we analyzed Illumina short-reads of 994 whole genomes representing ∼ 60 sheep breeds/populations at varied altitudes, PacBio High fidelity (HiFi) reads of 13 breeds, and 96 transcriptomes from 12 sheep organs. Association testing between the inhabited altitudes and 34,298,967 variants was conducted to investigate the genetic architecture of altitude adaptation. Highly accurate HiFi reads were used to complement the current ovine reference assembly at the most significantly associated ß-globin locus and to validate the presence of two haplotypes A and B among 13 sheep breeds. The haplotype A carried two homologous gene clusters: (1) HBE1, HBE2, HBB-like, and HBBC, and (2) HBE1-like, HBE2-like, HBB-like, and HBB; while the haplotype B lacked the first cluster. The high-altitude sheep showed highly frequent or nearly fixed haplotype A, while the low-altitude sheep dominated by haplotype B. We further demonstrated that sheep with haplotype A had an increased hemoglobin-O2 affinity compared with those carrying haplotype B. Another highly associated genomic region contained the EGLN1 gene which showed varied expression between high-altitude and low-altitude sheep. Our results provide evidence that the rapid adaptive evolution of advantageous alleles play an important role in facilitating the environmental adaptation of Tibetan sheep.

Clinical evolution of bladder carcinosarcoma: A case report and literature review.

RATIONALE: Bladder carcinosarcoma (BC) is a malignant tumor composed of a mixture of malignant epithelial and stromal components. Carcinosarcoma mostly occurs in the upper respiratory tract and upper gastrointestinal tract and is less common in the urinary system. The incidence of malignant tumors of the urinary system is <3%. It rarely occurs in the bladder and accounts for approximately 0.31% of all malignant bladder tumors. A literature review and this report will help to further improve our understanding, diagnosis, and treatment of bladder carcinosarcoma (BC). PATIENT CONCERN: We describe the case of an 80-year-old female patient who was admitted to the hospital with a history of intermittent hematuria for 3 years. Furthermore, total cystectomy was refused when a BC was diagnosed. Palliative resection surgery was necessary because of the recurrent hematuria and abdominal pain. DIAGNOSES: Pathologically confirmed BC after surgery. INTERVENTIONS: The patient's first transurethral resection of bladder tumor (TURBT) was diagnosed as BC. However, the patient refused a total cystectomy. Two months after intravesical treatment with epirubicin, bladder tumor recurrence was observed during follow-up cystoscopy. The patient underwent a second TURBT for hemostatic treatment due to persistent hematuria. Due to hematuria and abdominal pain, a third TURBT was performed to reduce tumor size and stop bleeding. Finally, tumor recurrence resulted in bilateral hydronephrosis, and the patient underwent bilateral renal catheter drainage guided by B-ultrasound. OUTCOMES: Bladder carcinosarcoma caused uremia, electrolyte imbalance, and sepsis. Approximately 19 months after the discovery of the tumor, the patient died. LESSONS: Radical bladder resection is recommended once a BC is diagnosed. By reporting the cases and reviewing the literature in the database, we will summarize the epidemiology, origin, etiology, clinical features, existing treatments, and prognostic factors of BC, and propose new prospects for BC therapy.

The functional impact on donor vessel following transcatheter closure of coronary artery fistulas-a retrospective study using QFR analysis.

Background: The impact of transcatheter closure of coronary artery fistula (CAF) and residual shunt after occlusion on improving blood flow in the donor vessel remains uncertain. Objectives: To evaluate the functional impact on the donor vessel following CAFs closure using QFR (Quantitative Flow Ratio) analysis. Methods: A total of 46 patients with 48 CAFs who underwent transcatheter closure at Shanghai Chest Hospital and Shuguang Hospital between March 2015 and August 2023 were included in the review. The clinical, angiographic details, and QFR data were subjected to analysis. The size of the fistulae was defined according to the ratio between the diameters of the fistulae and the largest diameter of the coronary vessel not feeding the coronary fistula. Results: Among 48 CAFs, the average diameter of the fistulae ostium was 3.19 ± 1.04 mm, while the mean diameter of the donor vessel segment following fistulae was 3.45 ± 1.01 mm. The mean QFR value of the donor vessels with medium CAFs was found to be significantly lower than those with small CAFs (0.93 ± 0.10 vs. 0.98 ± 0.03; p < 0.05). Furthermore, the mean QFR value of donor vessels with medium CAFs was observed to be significantly improved after occlusion (0.99 ± 0.01 vs. 0.93 ± 0.10; p = 0.01). However, there was no statistical difference in the mean QFR value of donor vessels with small CAFs before and after occlusion (0.98 ± 0.03 vs. 0.98 ± 0.02; p > 0.05). Moreover, the changes in QFR were more pronounced in donor vessels with medium CAFs compared to those with small CAFs after occlusion (0.06 ± 0.10 vs. 0.005 ± 0.012; p = 0.01). There is no statistical difference in the mean QFR variation and QFR variation rate between donor vessels with CAFs that occurred residual shunt and those without residual shunt after occlusion (p > 0.05). Conclusions: The presence of medium CAFs has a significant impact on the blood flow of the donor vessel, as compared to small CAFs, and may benefit from occlusion. A small residual shunt has no significant impact on the effectiveness of CAFs occlusion in enhancing donor blood flow.

Traditional Chinese medicine and plant-derived natural products in regulating triglyceride metabolism: Mechanisms and therapeutic potential.

The incidence of cardiometabolic disease is increasing globally, with a trend toward younger age of onset. Among these, atherosclerotic cardiovascular disease is a leading cause of mortality worldwide. Despite the efficacy of traditional lipid-lowering drugs, such as statins, in reducing low-density lipoprotein cholesterol levels, a significant residual risk of cardiovascular events remains, which is closely related to unmet triglyceride (TG) targets. The clinical application of current TG-lowering Western medicines has certain limitations, necessitating alternative or complementary therapeutic strategies. Traditional Chinese medicine (TCM) and plant-derived natural products, known for their safety owing to their natural origins and diverse biological activities, offer promising avenues for TG regulation with potentially fewer side effects. This review systematically summarises the mechanisms of TG metabolism and subsequently reviews the regulatory effects of TCM and plant-derived natural products on TG metabolism, including the inhibition of TG synthesis (via endogenous and exogenous pathways), promotion of TG catabolism, regulation of fatty acid absorption and transport, enhancement of lipophagy, modulation of the gut microbiota, and other mechanisms. In conclusion, through a comprehensive analysis of recent studies, this review consolidates the multifaceted regulatory roles of TCM and plant-derived natural products in TG metabolism and elucidates their potential as safer, multi-target therapeutic agents in managing hypertriglyceridemia and mitigating cardiovascular risk, thereby providing a basis for new drug development.

Corrigendum to "Enterococcus durans 98D alters gut microbial composition and function to improve DSS-induced colitis in mice" [Volume 10, Issue 7, 15 April 2024, e28486].

[This corrects the article DOI: 10.1016/j.heliyon.2024.e28486.].

Bioprinted research models of urological malignancy.

Urological malignancy (UM) is among the leading threats to health care worldwide. Recent years have seen much investment in fundamental UM research, including mechanistic investigation, early diagnosis, immunotherapy, and nanomedicine. However, the results are not fully satisfactory. Bioprinted research models (BRMs) with programmed spatial structures and functions can serve as powerful research tools and are likely to disrupt traditional UM research paradigms. Herein, a comprehensive review of BRMs of UM is presented. It begins with a brief introduction and comparison of existing UM research models, emphasizing the advantages of BRMs, such as modeling real tissues and organs. Six kinds of mainstream bioprinting techniques used to fabricate such BRMs are summarized with examples. Thereafter, research advances in the applications of UM BRMs, such as culturing tumor spheroids and organoids, modeling cancer metastasis, mimicking the tumor microenvironment, constructing organ chips for drug screening, and isolating circulating tumor cells, are comprehensively discussed. At the end of this review, current challenges and future development directions of BRMs and UM are highlighted from the perspective of interdisciplinary science.

Lactobacillus-Polydopamine System for Targeted Drug Delivery in Overactive Bladder: Evidence from Bladder Cell Spheroids, Rat Models, and Urinary Microbiome Profiling.

Introduction: Overactive bladder (OAB) is a highly prevalent condition with limited treatment options due to poor efficacy, side effects, and patient compliance. Novel drug delivery systems that can target the bladder wall may improve OAB therapy. Methods: We explored a polydopamine (PDA)-coated lactobacillus platform as a potential carrier for localized OAB treatment. Urinary microbiome profiling was performed to identify the presence of lactobacillus in healthy and OAB groups. Lactobacillus-PDA nanoparticles were synthesized and characterized by electron microscopy and spectrophotometry. A rat bladder perfusion model and human bladder smooth muscle cell spheroids were used to assess the distribution and penetration of the nanoparticles. The efficacy of the Lactobacillus-PDA system (LPS) for delivering the antimuscarinic drug solifenacin was evaluated in an OAB rat model. Results: Urinary microbiome profiling revealed lactobacillus as a dominant genus in both healthy and OAB groups. The synthesized Lactobacillus-PDA nanoparticles exhibited uniform size and optical properties. In the rat bladder perfusion model, the nanoparticles distributed throughout the bladder wall and smooth muscle without toxicity. The nanoparticles also penetrated human bladder smooth muscle cell spheroids. In the OAB rat model, LPS facilitated the delivery of solifenacin and improved treatment efficacy. Discussion: The results highlight LPS as a promising drug carrier for targeted OAB therapy via penetration into bladder tissues. This bacteriotherapy approach may overcome limitations of current systemic OAB medications. Lactobacillus, a probiotic bacterium present in the urinary tract microbiome, was hypothesized to adhere to and penetrate the bladder wall when coated with PDA nanoparticles, making it a suitable candidate for localized drug delivery.

A New Constitutive Model Based on Taylor Series and Partial Derivatives for Predicting High-Temperature Flow Behavior of a Nickel-Based Superalloy.

Ni-based superalloys are widely used in aerospace applications. However, traditional constitutive equations often lack the necessary accuracy to predict their high-temperature behavior. A novel constitutive model, utilizing Taylor series expansions and partial derivatives, is proposed to predict the high-temperature flow behavior of a nickel-based superalloy. Hot compression tests were conducted at various strain rates (0.01 s-1, 0.1 s-1, 1 s-1, and 10 s-1) and temperatures (850 °C to 1200 °C) to gather comprehensive experimental data. The performance of the new model was evaluated against classical models, specifically the Arrhenius and Hensel-Spittel (HS) models, using metrics such as the correlation coefficient (R), root mean square error (RMSE), sum of squared errors (SSE), and sum of absolute errors (SAE). The key findings reveal that the new model achieves superior prediction accuracy with an R value of 0.9948 and significantly lower RMSE (22.5), SSE (16,356), and SAE (5561 MPa) compared to the Arrhenius and HS models. Additionally, the stability of the first-order partial derivative of logarithmic stress with respect to temperature (∂lnσ/∂T) indicates that the logarithmic stress-temperature relationship can be approximated by a linear function with minimal curvature, which is effectively described by a second-degree polynomial. Furthermore, the relationship between logarithmic stress and logarithmic strain rate (∂lnσ/∂lnε˙) is more precisely captured using a third-degree polynomial. The accuracy of the new model provides an analytical basis for finite element simulation software. This helps better control and optimize processes, thus improving manufacturing efficiency and product quality. This study enables the optimization of high-temperature forming processes for current superalloy products, especially in aerospace engineering and materials science. It also provides a reference for future research on constitutive models and high-temperature material behavior in various industrial applications.

Enhancing Hydraulic Lime Mortar with Metakaolin: A Study on Improving Restoration Materials for Historic Buildings.

This study investigates the enhancement of hydraulic lime mortar (HLM) using varying contents of metakaolin (MK) to improve its application in the restoration of historic buildings. Samples from historic structures were analyzed, and the effects of different MK contents on the physical and mechanical properties of HLM were examined. The reaction mechanism and microstructural changes were evaluated using XRD and SEM analysis. The results indicated that increasing MK levels in HLM led to a decrease in fluidity, with fluidity reducing by 4.8% at 12% MK. The addition of MK increased water consumption for standard consistency by 5.4% and shortened the final setting time by 10.2%. MK consumption promoted secondary hydration, enhancing compressive strength by up to 98.1% and flexural strength by up to 55.1%, and increasing bonding strength by 26.9%. The density of HLM improved with MK addition, slightly reducing moisture content by 4.5% and water absorption by 4.6%, while the water vapor transmission properties decreased by 50.9%, indicating reduced porosity. The elastic modulus of the mortar increased significantly from 2.19 GPa to 7.88 GPa with the addition of MK, enhancing rigidity and crack resistance. The optimal blend for restoration materials was found to be 9.0% MK and 25.0% heavy calcium carbonate and was characterized by moderate mechanical strength, enhanced early strength, commendable permeability, minimal risk of cracking, and ease of application. This blend is highly suitable for the rehabilitation of historic structures.

Enhanced choroid plexus segmentation with 3D UX-Net and its association with disease progression in multiple sclerosis.

BACKGROUND: The choroid plexus (CP) is suggested to be closely associated with the neuroinflammation of multiple sclerosis (MS). Segmentation based on deep learning (DL) could facilitate rapid and reproducible volume assessment of the CP, which is crucial for elucidating its role in MS. PURPOSE: To develop a reliable DL model for the automatic segmentation of CP, and further validate its clinical significance in MS. METHODS: The 3D UX-Net model (3D U-Net used for comparison) was trained and validated on T1-weighted MRI from a cohort of 216 relapsing-remitting MS (RRMS) patients and 75 healthy subjects. Among these, 53 RRMS with baseline and 2-year follow-up scans formed an internal test set (dataset1b). Another 58 RRMS from multi-center data served as an external test set (dataset2). Dice coefficient was computed to assess segmentation performance. Compare the correlation of CP volume obtained through automatic and manual segmentation with clinical outcomes in MS. Disability and cognitive function of patients were assessed using the Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT). RESULTS: The 3D UX-Net model achieved Dice coefficients of 0.875 ± 0.030 and 0.870 ± 0.044 for CP segmentation on dataset1b and dataset2, respectively, outperforming 3D U-Net's scores of 0.809 ± 0.098 and 0.601 ± 0.226. Furthermore, CP volumes segmented by the 3D UX-Net model aligned consistently with clinical outcomes compared to manual segmentation. In dataset1b, both manual and automatic segmentation revealed a significant positive correlation between normalized CP volume (nCPV) and EDSS scores at baseline (manual: r = 0.285, p = 0.045; automatic: r = 0.287, p = 0.044) and a negative correlation with SDMT scores (manual: r = -0.331, p = 0.020; automatic: r = -0.329, p = 0.021). In dataset2, similar correlations were found with EDSS scores (manual: r = 0.337, p = 0.021; automatic: r = 0.346, p = 0.017). Meanwhile, in dataset1b, both manual and automatic segmentation revealed a significant increase in nCPV from baseline to follow-up (p < 0.05). The increase of nCPV was more pronounced in patients with disability worsened than stable patients (manual: p = 0.023; automatic: p = 0.018). Patients receiving disease-modifying therapy (DMT) exhibited a significantly lower nCPV increase than untreated patients (manual: p = 0.004; automatic: p = 0.004). CONCLUSION: The 3D UX-Net model demonstrated strong segmentation performance for the CP, and the automatic segmented CP can be directly used in MS clinical practice. CP volume can serve as a surrogate imaging biomarker for monitoring disease progression and DMT response in MS patients.

May Measurement Month 2021: an analysis of blood pressure screening results from China.

We reported findings from participants screened during the May Measurement Month 2021 in China, which aimed to raise awareness of raised blood pressure (BP), and to investigate the risk factors of BP. The study participants were adults (≥18 years), ideally in whom BP had not been measured in the previous year. Blood pressure was measured three times consecutively with 1 min intervals in the sitting position, using a validated upper-arm cuff automated BP monitor (Omron HEM-7081IT), and transmitted to a central cloud database via a smartphone app. The measurement was performed in 218 844 participants in 183 sites across 31 China provinces. The mean (standard deviation) age was 47.0 (15.7) years, and 51.8% (n = 113 466) were women. The mean systolic/diastolic BP was 120.2/77.5 mmHg. Among 57 178 (26.1%) participants with hypertension, the awareness, treatment, and control rates of hypertension were 30.4% (n = 17 354), 28.7% (n = 16 369), and 17.1% (n = 9743), respectively. After adjustment for age, sex, and use of antihypertensive medication, both systolic and diastolic BP were significantly (P ≤ 0.01) higher in current smokers (n = 22 344, +0.4/+0.7 mmHg) and with moderate (n = 4780, +1.4/+4.2 mmHg) or daily alcohol intake (n = 2427, +1.3/+2.5 mmHg). Blood pressure was lower in those reporting regular exercise (n = 32 328, -2.2/-1.4 mmHg). In addition, individuals with previous COVID-19 vaccination had lower systolic and diastolic BP (n = 88 945, -1.8/-1.5 mmHg, P ≤ 0.001). In conclusion, our study showed that long-term large-scale screening for hypertension is feasible, and there is a strong association between BP and major lifestyle factors.

Impact of adrenalectomy on hypertension in patients with nonfunctional adrenal tumors: a retrospective study.

OBJECTIVE: To investigate the impact of adrenalectomy on hypertension in patients with nonfunctional adrenal tumors. SUBJECTS AND METHODS: Between January 2020 and October 2022, patients with adrenal lesions were retrospectively screened for nonfunctional adrenal tumors at the Zhongnan Hospital of Wuhan University. All patients underwent detailed endocrinological examination and computed tomography to characterize the lesions. One year after discharge, follow-up blood pressure (BP) was assessed and compared to the blood pressure on admission. Univariate analysis and multivariate regression analysis were performed to determine factors predicting favorable hypertension outcomes after adrenalectomy. RESULTS: A total of 309 patients were found to be eligible, including 123 who underwent adrenalectomy. Patients who underwent adrenalectomy were stratified into two groups: (Bancos I (2022) Adrenal Incidentalomas: Insights Into Prevalence. Ann Intern Med 175:1481-1482. https://doi.org/10.7326/M22-2600 ) those with improved hypertension (n = 71), and (Fassnacht M, Tsagarakis S, Terzolo M, Tabarin A, Sahdev A, Newell-Price J et al. (2023) European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol 189:G1-42. https://doi.org/10.1093/ejendo/lvad066 ) those without improved hypertension (n = 52). In contrast, the blood pressure levels of conservatively treated patients remained relatively stable 1 year after discharge. Univariate analysis and multivariate regression analysis showed that body mass index (BMI) and duration of hypertension were significantly different between the hypertension improvement group and the non-improvement group (p < 0.05). CONCLUSION: Adrenalectomy has been shown to be effective in improving hypertension in certain patients with nonfunctional adrenal tumors. BMI and duration of hypertension were independent factors associated with favorable hypertension outcomes after adrenalectomy.