Search

Alcoholic steatohepatitis (ASH) is a liver disease characterized by steatosis, inflammation, and necrosis of the liver tissue as a result of excessive alcohol consumption. Pregnane X receptor (PXR) is a xenobiotic nuclear receptor best known for its function in the transcriptional regulation of drug metabolism and disposition. Clinical reports suggested that the antibiotic rifampicin, a potent human PXR activator, is a contraindication in alcoholics, but the mechanism was unclear. In this study, we showed that the hepatic expression of fatty acid binding protein 4 (FABP4) was uniquely elevated in ASH patients and a mouse model of ASH. Pharmacological inhibiting FABP4 attenuated ASH in mice. Furthermore, treatment of mice with the mouse PXR agonist pregnenolon-16 α -carbonitrile (PCN) induced the hepatic and circulating levels of FABP4 and exacerbated ASH in a PXR-dependent manner. Our mechanism study established FABP4 as a transcriptional target of PXR. Treatment with andrographolide, a natural compound and dual inhibitor of PXR and FABP4, alleviated mice from ASH. In summary, our results showed that the PXR–FABP4 gene regulatory axis plays an important role in the progression of ASH, which may have accounted for the contraindication of rifampicin in patients of alcoholic liver disease. Pharmacological inhibition of PXR and/or FABP4 may have its promise in the clinical management of ASH. This study showed that the PXR–FABP4 gene regulatory axis plays an important role in the progression of alcoholic steatohepatitis. [Display omitted] [ABSTRACT FROM AUTHOR]

To demonstrate the feasibility and short-term outcomes of Robot-Assisted Single Port vaginal NOTES (RSP-vNOTES) for total hysterectomy, with or without endometriosis resection for all stages. Retrospective case series. Single academic tertiary care hospital in Houston, Texas, USA. Twenty-eight adult women with chronic pelvic pain who underwent RSP-vNOTES hysterectomy, with or without endometriosis resection. Hysterectomy with or without excision of endometriosis via single-port robot-assisted vNOTES platform (Intuitive Da Vinci SP Platform). Twenty-eight patients with a mean age of 40.1 years (range 24.0–54.0 years), mean BMI 28.5 kg/m2 (range 19.5–48.4 kg/m2), underwent RSP-vNOTES from November 11, 2023 to May 7, 2024. Five (17.9%) patients underwent solely a hysterectomy, while 23 (82.1%) patients underwent additional endometriosis resection; 28.6% with stage I, 25.0% stage II, 7.1% stage III, and 21.4% with stage IV. Mean total operative time was 188.7 minutes (range 135.0–427.0 minutes), with robot dock time of 2.9 minutes (range 1.0–10.0 minutes), robot console time of 97.3 minutes (range 51.0–221.0 minutes), and hysterectomy time of 55.3 minutes (range 24.0–170.0 minutes). Estimated blood loss averaged 32.1 mL (range 25.0–50.0 mL). One case required a mini-laparotomy as the irregularly shaped 1668 g fibroid uterus was unable to be removed vaginally. Complications included one case of vaginal cuff cellulitis and one case of urinary tract infection. Our findings indicate that RSP-vNOTES, a novel single-port surgical approach, presents a promising alternative surgical platform in vaginal surgeries. [ABSTRACT FROM AUTHOR]

Cell senescence and metabolic reprogramming are significant features of diabetic kidney disease (DKD). However, the underlying mechanisms between cell senescence and metabolic reprogramming are poorly defined. Here, we report that retinoid X receptor α (RXRα), a key nuclear receptor transcription factor, regulates cell senescence and metabolic reprogramming in DKD. Through high-throughput sequencing, bioinformatic analysis and experimental validation, we confirmed the critical role of RXRα in promoting cell senescence and metabolic dysregulation in renal tubular epithelial cells (RTECs) induced by lipid overload. In vivo, in situ injection of AAV9- shRxra into the kidney reduced proteinuria, RTECs senescence and insulin resistance in DKD mice. In vitro , knockdown of RXRα markedly improved G2/M phase arrest and suppressed the expression of senescence-associated secretory phenotypes (SASPs). Protein-protein interaction (PPI) analysis and unbiased bioinformatics were employed to identify the direct interactions between RXRα and the mineralocorticoid receptor (MR), which were subsequently validated through coimmunoprecipitation. Gene network analysis revealed the collaborative regulatory role of RXRα and MR in RTECs senescence. In an accelerated aging mouse model, treatment with a MR antagonist has been shown to inhibite the RXRα/MR signaling, improve RTECs senescence, and reduce interstitial fibrosis and lipid deposition in the kidneys. These findings indicate that inhibition of RXRα/MR signaling could alleviate cell senescence during metabolic disorders. Thus, our study revealed that RXRα/MR signaling serves as a critical regulatory factor mediating the crosstalk between cell senescence and metabolic reprogramming, shedding light on a novel mechanism for targeting cell senescence and metabolic dysregulation in DKD. [ABSTRACT FROM AUTHOR]

Metastases from gastric adenocarcinoma (GAC) lead to high morbidity and mortality. Developing innovative and effective therapies requires a comprehensive understanding of the tumor and immune biology of advanced GAC. Yet, collecting matched specimens from advanced, treatment-naïve patients with GAC poses a significant challenge, limiting the scope of current research, which has focused predominantly on localized tumors. This gap hinders deeper insight into the metastatic dynamics of GAC. We performed in-depth single-cell transcriptome and immune profiling on 68 paired, treatment-naïve, primary metastatic tumors to delineate alterations in cancer cells and their tumor microenvironment during metastatic progression. To validate our observations, we conducted comprehensive functional studies both in vitro and in vivo, using cell lines and multiple patient-derived xenograft and novel mouse models of GAC. Liver and peritoneal metastases exhibited distinct properties in cancer cells and dynamics of tumor microenvironment phenotypes, supporting the notion that cancer cells and their local tumor microenvironments co-evolve at metastatic sites. Our study also revealed differential activation of cancer meta-programs across metastases. We observed evasion of cancer cell ferroptosis via GPX4 up-regulation during GAC progression. Conditional depletion of Gpx4 or pharmacologic inhibition of ferroptosis resistance significantly attenuated tumor growth and metastatic progression. In addition, ferroptosis-resensitizing treatments augmented the efficacy of chimeric antigen receptor T-cell therapy. This study represents the largest single-cell dataset of metastatic GACs to date. High-resolution mapping of the molecular and cellular dynamics of GAC metastasis has revealed a rationale for targeting ferroptosis defense in combination with chimeric antigen receptor T-cell therapy as a novel therapeutic strategy with potential immense clinical implications. A comprehensive single-cell tumor and immune atlas of metastatic gastric adenocarcinomas is presented, uncovering molecular and cellular dynamics during metastasis and proposing a novel therapeutic strategy with potential clinical implications. [ABSTRACT FROM AUTHOR]

Heavy metals can easily accumulate in soil and river sediment due to their non-degradability, which seriously endangers the balance of the ecosystem and human health. Thus, research on heavy metals in soil-river composite ecosystems has great significance for risk mitigation. As a seasonal river in a semi-arid region (Yuzhong county) in northwest China, the Wanchuan River supports nearly 500,000 people, but has been polluted by the heavy metals from industrial wastes and sewage discharges. To protect precious water resources and soil ecosystems, it is urgent to do heavy metal research in the Wanchuan River basin. Towards this end, the current study collected samples of soil and river sediment in this basin, and analyzed the distribution characteristics, health risks, and pollution sources of heavy metals, based on the pollution index evaluation method, health risk assessment, a geostatistical model, and the positive matrix factorization (PMF) model. The research results show that the contents of heavy metals in soil and river sediment were equivalent. However, contamination levels of heavy metals in stream sediment fell below that in soil. The results from the PMF model pointed out that natural sources contributed remarkably to the contents of heavy metals in soil, while industrial sources had the highest contribution to the contents of heavy metals in river sediment. According to the health risk assessment, among all selected metals, Cr brought about the highest carcinogenic risk, while As generated the highest non-carcinogenic risk. Source-oriented health risk assessment showed that natural sources (37%) and agricultural sources (50%), respectively, contributed most to the non-carcinogenic risks and carcinogenic risks induced by soil metals. Industrial sources contributed most both to the non-carcinogenic risks (46%) and carcinogenic risks (37%) induced by river sediment metals. The current research may offer theoretical bases for heavy metal pollution treatment in the soil-river continuum. [Display omitted] • The soil-river continuum of the Wanchuan river was slightly polluted by heavy metals. • The distribution of heavy metals in soil and sediment was similar, but soil had a higher pollution degree than sediment. • Ingestion pathway induced the higher health risk than inhalation and dermal exposure. • Natural and agricultural sources were the main contributors to soil heavy metals, while industry dominated in sediment. [ABSTRACT FROM AUTHOR]

The different fate of liposomes among species has been discovered and mentioned in many studies, but the underlying mechanisms have not been explored. In the present work, we concentrated on the in vivo fate of PEGylated liposomes (sLip) in three commonly used species (mice, rats, and dogs). It was exhibited that the accelerated blood clearance (ABC) phenomenon and hypersensitivity in large animals (beagle dogs) were much more significant than that in rodents. We demonstrated that anti-PEG IgM (partially) and complement (mostly) determined the elimination of sLip and linked the distinct interspecies performances with the diverse complement capacity among species. Based on the data from animals and clinical patients, it was revealed that the fate of sLip in large animals was closer to that in humans, for the sufficient complement capacity could expose the potential adverse reactions caused by anti-PEG antibodies. Our results suggested that the distinctive interspecies performances of sLip were highly related to the physiological variabilities among species, which should not be overlooked in the innovation and translation of nanomedicines. Anti-PEG IgM (partially) and complement (mostly) determined the elimination of sLip and linked the distinct interspecies performances with the diverse complement capacity among species. [Display omitted] [ABSTRACT FROM AUTHOR]

To explore the risk factors associated with local regeneration of the treated uterine fibroids (UFs) after microwave ablation (MWA) and to develop a nomogram model for predicting the risk of local regeneration. Retrospective study. The Eighth Affiliated Hospital of Sun Yat-Sen University. Patients with UFs who underwent MWA at our hospital between October 2020 and April 2023 were included. MWA was used for the treatment of UFs. A total of 47 patients with 68 fibroids were included into this study. Over a median follow-up of 13 months (interquartile range, 8–22 months), local regeneration occurred in 11 UFs. The clinical and imaging characteristics of these patients were recorded and compared. Risk factors for local regeneration were determined through univariate and multivariate Cox regression analysis. Multivariate analysis revealed that the fertility desires, larger size of UFs (≥95.3 cm3), and hyperenhancement of UFs on contrast-enhanced ultrasound were independent risk factors for local regeneration after MWA. A predictive nomogram was constructed to predict the local regeneration after MWA of UFs. The concordance index (C-index) (C-index, 0.924; internal validation C-index, 0.895) and the 1- and 2-year area under the curve values (0.962, 0.927) all indicated that the nomogram had good predictive performance. Calibration and decision curve analysis curves further confirmed the model's accuracy and clinical utility. Fertility desires, larger size of UFs, and hyperenhancement on contrast-enhanced ultrasound were independent predictors of UFs local regeneration after MWA in our study. The nomogram constructed based on the abovementioned independent risk factors may help predict which UFs will develop local regeneration after MWA. [ABSTRACT FROM AUTHOR]

In order to realize high-precision diagnosis of bearings faults in a multi-sensor detection environment, a fault diagnosis method based on two-stage signal fusion and deep multi-scale multi-sensor networks is proposed. Firstly, the signals are decomposed and fused using weighted empirical wavelet transform to enhance weak features and reduce noise. Secondly, an improved random weighting algorithm is proposed to perform a second weighted fusion of the signals to reduce the total mean square error. The fused signals are input into the deep multi-scale residual network, the feature information of different convolutional layers is extracted through dilated convolution, and the features are fused using pyramid theory. Finally, the bearings states are classified according to the fusion features. Experiment results show the effectiveness and superiority of this method. • Application range of the traditional random weighted fusion algorithm is extended. • A new signal fusion method based on two-stage weighting is constructed. • An improved deep residual network is proposed to realize multi-scale features extraction and fusion enhancement. [ABSTRACT FROM AUTHOR]

The study aimed to develop a model to predict the risk of sarcopenia in gastrointestinal cancer patients. The goal was to identify these patients early and classify them into different risk categories based on their likelihood of developing sarcopenia. This study evaluated risk factors for sarcopenia in patients with gastrointestinal cancers through a systematic review and meta-analysis. The natural logarithm of the combined risk estimate for each factor was used as a coefficient to assign scores within the model for risk prediction. Data from 270 patients with gastrointestinal cancers, collected between October 2023 and April 2024, was used to assess the predictive performance of the scoring model. The analysis included 17 studies that included 9405 patients with gastrointestinal cancers, out of which 4361 had sarcopenia. The model identified several significant predictors of sarcopenia, including age (OR = 2.45), sex (OR = 1.15), combined diabetes (OR = 2.02), neutrophil-to-lymphocyte ratio (NLR) category (OR = 1.61), TNM stage (OR = 1.61), and weight change (OR = 1.60). Model validation was performed using an external cohort through logistic regression, resulting in an area under the curve (AUC) of 0.773. This model attained a sensitivity of 0.714 and a specificity of 0.688 and ultimately selected 16.5 as the ideal critical risk score. Furthermore, an AUC of 0.770 was obtained from Bayesian model validation; the optimal critical risk score was determined to be 19.0, which corresponds to a sensitivity of 0.658 and a specificity of 0.847. The model of risk prediction developed through systematic review and meta-analysis demonstrates substantial for sarcopenia in patients with gastrointestinal cancers. Its clinical usability facilitates the screening of patients at high risk for sarcopenia. [ABSTRACT FROM AUTHOR]

The predicted Bridge Condition Index (BCI) is a guiding indicator for formulating preventive maintenance strategies for bridges and is hardly available even if using the most advanced neural network prediction model, owing to the few measured BCIs and neural network model defects. In this paper, an improved Back-Propagation Neural Network (BPNN) model named CPSO-BP-MC is proposed to predict BCI, which has a BPNN as its core, combined with the Coordinated Particle Swarm Optimization (CPSO) algorithm aims to faster convergence and avoid local optimal solution even with less training sample, and the Markov Chain (MC) algorithm aims to further revise the fluctuation of CPSO-BP prediction output due to maintenance and reinforcement. A case study is presented to demonstrate the efficiency of CPSO-BP-MC predicting BCI with fewer training samples. Comparing the predicted BCI of CPSO-BP-MC with the measured BCI and other models, the results show that CPSO-BP-MC converges faster than other models, and can predict the BCI more stably and accurately, and the error between prediction and measured BCI is less than 3 %. [ABSTRACT FROM AUTHOR]

Obesity and metabolic abnormalities were associated with an increased risk of cardiovascular disease. However, it is unclear how metabolic weight phenotypes relate to cardiovascular diseases in postmenopausal women. This study aimed to explore the relationships in postmenopausal women. We included 15,575 postmenopausal women aged 35–75 years (median age, 60.6) without cardiovascular disease at baseline from a subcohort of the China Patient-centered Evaluative Assessment of Cardiac Events Million Persons Project. Metabolically unhealthy phenotype was defined as having ≥2 risk factors of metabolic syndrome: blood pressure ≥130/85 mm Hg or current use of antihypertensive drugs, fasting glucose ≥5.6 mmol/L or current use of antidiabetic agents, triglycerides ≥1.7 mmol/L, and high-density lipoprotein cholesterol <1.3 mmol/L. Cox regression analysis was used to evaluate the risks of cardiovascular diseases. Over a median follow-up period of 3.55 (interquartile range, 2.59–4.44) years, a total of 1354 cardiovascular events occurred. Compared to metabolically healthy normal weight, the multivariate-adjusted hazard ratios and their 95% confidence intervals were 1.41 (1.16–1.72) for metabolically unhealthy normal weight, 1.42 (1.16–1.73) for metabolically healthy overweight/obesity, and 1.75 (1.48–2.08) for metabolically unhealthy overweight/obesity. Subdividing overweight/obesity into separate groups revealed higher total cardiovascular disease risk only in metabolically unhealthy individuals across body mass index categories. In postmenopausal women, both metabolically healthy overweight/obesity and metabolically unhealthy normal weight were associated with a higher risk of cardiovascular disease compared to metabolically healthy normal weight, and the greatest risk was observed in the metabolically unhealthy overweight/obesity category. • Metabolically unhealthy postmenopausal women have a higher risk of cardiovascular disease than those who are metabolically healthy. • Metabolic risk factors increase the risk of cardiovascular disease even in individuals with normal weight. • Metabolically unhealthy overweight/obese individuals need close monitoring; normal-weight individuals should not be overlooked. [ABSTRACT FROM AUTHOR]

The regulation of intracellular ionic homeostasis to trigger antigen-specific immune responses has attracted extensive interest in tumor therapy. In this study, we developed a dual-pathway nanoreactor, Au-Cu 2-x Se@ZIF-8@P18 NPs (ACS-Z-P NPs), which targets danger-associated molecular patterns (DAMPs) and releases Zn2+ and reactive oxygen species (ROS) within the tumor microenvironment (TME). Zn2+ released from the metal–organic frameworks (MOFs) was deposited in the cytoplasm, leading to aberrant transcription levels of intracellular zinc-regulated proteins and DNA damage, thereby inducing pyroptosis and immunogenic cell death (ICD) dependent on caspase1/gasdermin D (GSDMD) pathway. Furthermore, upon laser irradiation, ACS-Z-P NPs could break through the limitations of inherent defects of immunosuppression in TME, enhance ROS generation through a Fenton-like reaction cascade, which subsequently triggered the activation of inflammatory vesicles and the release of damage-associated molecular patterns (DAMPs). This cascade effect led to the amplification of pyroptosis and immunogenic cell death (ICD), thereby remodeling the immunosuppressed TME. Consequently, this process improved dendritic cell (DC) antigen presentation and augmented anti-tumor T-cell responses, effectively initiating antigen-specific immune responses and further enhancing pyroptosis and ICD. This study explores the therapeutic properties of these mechanisms in detail. The synthesized Au-Cu 2-x Se@ZIF-8@P18 nanoparticles (ACS-Z-Ps) can effectively enhance the bodyʼs immune response by regulating zinc ion levels within cells. This regulation leads to abnormal levels of zinc-regulated protein transcription and DNA damage, which induces cellular pyroptosis. As a result, antigen presentation to dendritic cells (DCs) is improved, and anti-tumor T-cell responses are enhanced. The ACS-Z-P NPs overcome the limitations of ROS deficiency and immunosuppression in the tumor microenvironment by using H 2 O 2 in the tumor microenvironment through a Fenton-like reaction. This leads to an increased production of ROS and O 2 , remodeling of the immunosuppressed tumor microenvironment, and enhanced induction of cell pyroptosis and immunogenic cell death. ACS-Z-P NPs targeted B16 cells using the photosensitizer P18 in combination with PDT treatment. This approach significantly inhibited the proliferation of B16 cells and effectively inhibited tumor growth. [Display omitted] [ABSTRACT FROM AUTHOR]

Alloying is one of the effective approaches to boost the discharge property of magnesium (Mg) anodes for primary Mg-air batteries and recently micro-alloying is highly recommended at the aim of developing advanced primary Mg system. In this study, micro-alloyed extruded Mg0.5Zn0.2Ge (in wt.%) alloy is evaluated as an anode candidate for primary Mg-air batteries in both half-cell and Mg-air full cell configurations, in comparison with commercially accepted Mg anodes, typified by as-cast HP Mg and extruded AZ31 alloy. The corrosion behavior at open circuit potential (OCP) condition of the three materials is also compared through electrochemical tests. Mg0.5Zn0.2Ge alloy displays the most negative OCP value and the highest corrosion resistance at OCP. During discharge, Mg0.5Zn0.2Ge anode exhibits low wasteful-discharge rate and homogeneous dissolution that gives rise to the absence of "chunk effect". Consequently, the anodic efficiency and specific capacity of Mg0.5Zn0.2Ge anode are superior to those of HP Mg and AZ31 anodes, e.g. 57.3% and 1257 mAh g−1 at 1 mA cm−2. Additionally, Mg-air battery based on Mg0.5Zn0.2Ge anode offers higher cell voltage and specific energy than those assembled with HP Mg and AZ31 anodes, which can be further optimized by addition of electrolyte additives. Therefore, micro-alloyed Mg0.5Zn0.2Ge alloy can serve as a promising candidate for anode material of primary Mg-air batteries. [ABSTRACT FROM AUTHOR]

It's a comparative study between bicycle and treadmill groups to observe the effects of high-intensity interval exercise training on knee health and articular cartilage volume in patients with obesity, thus to provide a scientific basis for the healthy exercise methods to lose weight. 60 patients with simple obesity were randomly divided into two groups of 30: the bicycle group and the treadmill group. Both groups received high-intensity interval exercise training, power bicycle training and moving treadmill training (MTT) were accepted respectively. Both groups received consecutive treatment for 12 weeks, five times a week, and every single time lasted for 30 min. Before and after treatment, the body mass index (BMI), the knee's articular cartilage volume was measured with magnetic resonance imaging (MRI),the pain of knee was assessed with visual analogue scale (VAS). Before and after each training session, the local skin temperature of the knee was measured with an electronic thermometer. After 12 weeks of treatment, the BMI was both decreased, the VAS and the local skin temperature of knee was increased significantly, the knee's articular cartilage volume in the treadmill group was reduced significantly, while the above indicators in the bicycle group did not change significantly, and the difference between the two groups was statistically significant (p < 0.001). Power bicycle training can avoid a decrease in the volume of knee joint cartilage, while MTT can easily lead to a decrease in the volume of knee joint cartilage, an increase in local skin temperature and pain of knee joint. [ABSTRACT FROM AUTHOR]

Arginine methylation, a vital post-translational modification, plays a pivotal role in numerous cellular functions such as signal transduction, DNA damage response and repair, regulation of gene transcription, mRNA splicing, and protein interactions. Central to this modification is the role of protein arginine methyltransferases (PRMTs), which have been increasingly recognized for their involvement in the pathogenesis of various respiratory diseases. This review begins with an exploration of the biochemical underpinnings of arginine methylation, shedding light on the intricate molecular regulatory mechanisms governed by PRMTs. It then delves into the impact of arginine methylation and the dysregulation of arginine methyltransferases in diverse pulmonary disorders. Concluding with a focus on the therapeutic potential and recent advancements in PRMT inhibitors, this article aims to offer novel perspectives and therapeutic avenues for the management and treatment of respiratory diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] • The initial subduction of the eastern CAOB began at ∼ 510 Ma. • Two distinct early Paleozoic subduction zones existed in the eastern CAOB. • The arcs developed from immaturity to maturity during early Paleozoic. This paper presents zircon U–Pb dating and Hf isotopic, and whole-rock geochemical and Sr–Nd isotopic data for early Paleozoic igneous rocks as well as zircon U–Pb dating for the sedimentary rocks of the Songnen Massif within the eastern Central Asian Orogenic Belt (CAOB), aiming to reveal arc magma evolution process. The zircon U–Pb dating results of the siltstone of the Xiaojingou Formation yielded 450 Ma, 471 Ma, 502 Ma, 773 Ma, 818 Ma and 949 Ma age peaks, as well as multi-episodic Paleo-proterozoic ages (2486-1612 Ma), implying its deposition time is younger than ∼ 450 Ma. The zircon U–Pb dating results reveal that the Songnen Massif exists three episodes of volcanic rocks of the middle Cambrian (502 Ma), Middle Ordovician (453-449 Ma) and the Silurian (435-420 Ma). The middle Cambrian basalts are low-K tholeiitic to calc-alkaline series, weakly depleted ε Hf (t) and ε Nd (t) values. They were derived from the weakly depleted mantle metasomatized by slab fluid in an immature island arc setting. The Middle Ordovician to Silurian volcanic rocks show SiO 2 of 49.4–58.1 wt%, plotting into high-K calc-alkaline series, which are also featured by higher Th/Nd and (Hf/Sm) PM ratios, together with moderate depleted ε Nd (t) values, suggesting their derivation of the depleted mantle wedge metasomatized by sediment-derived melt. In contrast, coeval early Paleozoic volcanic rocks in the eastern Xing'an Massif with the MORB-like ε Nd (t) values are characterized by an origin of the depleted mantle wedge and the distinct interaction of oceanic crust melt and mantle peridotite. Combined with the variation of calculated crust thickness, we suggested that there was a continental arc in the eastern Songnen Massif, which developed from immaturity to maturity during middle Cambrian to Silurian, while the early Paleozoic island arc in the eastern Xing'an Massif is characterized by ocean ridge subduction process. [ABSTRACT FROM AUTHOR]

• Evidence before this study. • Previous studies have demonstrated the association between residual inflammation and adverse clinical outcomes in patients with de novo lesions treated with PCI and statins. However, in patients with ISR, whether clinicians should choose a second LDL-C lowering agent, or alternatively initiate the anti-inflammatory therapy, remains uncertain and controversial. • Added value of this study. • Among 2079 patients who were undergoing PCI for ISR lesions, residual inflammatory risk (as measured by hsCRP) was a stronger predictor of adverse cardiovascular outcomes compared with residual cholesterol risk (as detected by LDL-C). • Implications of all the available evidence. • In patients with ISR underwent successful PCI, inflammation appears to be a stronger driver of residual cardiovascular event than cholesterol level. These data have substantial implications for the anti-inflammation as a therapeutic target to improve long-term outcomes in this special population. To evaluate the relationships between residual inflammatory risk [assessed by high-sensitivity C-reactive protein (hsCRP)], residual cholesterol risk [assessed by low-density lipoprotein cholesterol (LDL-C)] and clinical outcomes among patients who underwent percutaneous coronary intervention (PCI) for in-stent restenosis (ISR) lesions. Between January 2017 and December 2018, a total of 2079 patients who underwent PCI for ISR were consecutively enrolled. The primary outcome was the rate of major adverse cardiac events (MACE), defined as a composite endpoint of all-cause death, spontaneous myocardial infarction (MI), or repeat revascularization. During a median follow-up of 36 months, 436 MACEs occurred. Baseline hsCRP was significantly associated with MACE (highest versus lowest quartile, adjusted hazard ratio [aHR] 1.90 [95% CI, 1.39–2.59]; P < 0.001). By contrast, the baseline LDL-C quartile was not associated with MACE (highest versus lowest quartile, aHR 0.93 [95% CI, 0.71- 1.22]; P = 0.59). Compared with patients without residual risk (hsCRP <2 mg/L and LDL-C < 70 mg/dL), participants with both residual inflammatory and LDL-C risk (hsCRP ≥2 mg/L and LDL-C ≥ 70 mg/dL) (aHR, 1.39 [95% CI, 1.06–1.83]; P = 0.02) and those with residual inflammatory risk only (hsCRP ≥2 mg/L and LDL-C < 70 mg/dL) (aHR, 1.34 [95% CI, 1.01–1.72]; P = 0.04) had significantly higher risks of MACE. In the current cohort of patients after ISR PCI, inflammation assessed by hsCRP predicted higher risk of adverse clinical outcomes, whereas the level of LDL-C was not associated with adverse prognosis. [ABSTRACT FROM AUTHOR]

The degradation behavior of biodegradable Mg alloys has become a research hotspot in the fields about biodegradable metallic materials. While the most of the related publications mainly focused on the degradation rate of Mg-based materials, but rare to care about the changes of their mechanical properties during the immersion period, which can significantly affect their service performance. The link between residual strength and Mg degradation is not appreciated enough. In this work, a series media were constructed based on Hanks' solution, the effects of inorganic ions on the degradation rate and mechanical integrity of Mg-Zn-Y-Nd alloy were investigated. The results indicated that the degradation behavior of Mg alloy was mainly controlled by degradation products and there is no direct correspondence between the degradation rate change and mechanical integrity of Mg alloy. The relevant findings are beneficial for selecting the monitoring index in Mg corrosion tests and evaluating the service reliability of Mg alloys for biomedical applications. [ABSTRACT FROM AUTHOR]

To explore and validate the clinical value of ultrasound (US) viscosity imaging in differentiating breast lesions by combining with BI-RADS, and then comparing the diagnostic performances with BI-RADS alone. This multicenter, prospective study enrolled participants with breast lesions from June 2021 to November 2022. A development cohort (DC) and validation cohort (VC) were established. Using histological results as reference standard, the viscosity-related parameter with the highest area under the receiver operating curve (AUC) was selected as the optimal one. Then the original BI-RADS would upgrade or not based on the value of this parameter. Finally, the results were validated in the VC and total cohorts. In the DC, VC and total cohorts, all breast lesions were divided into the large lesion, small lesion and overall groups respectively. A total of 639 participants (mean age, 46 years ± 14) with 639 breast lesions (372 benign and 267 malignant lesions) were finally enrolled in this study including 392 participants in the DC and 247 in the VC. In the DC, the optimal viscosity-related parameter in differentiating breast lesions was calculated to be A′-S2-Vmax, with the AUC of 0.88 (95% CI: 0.84, 0.91). Using > 9.97 Pa.s as the cutoff value, the BI-RADS was then modified. The AUC of modified BI-RADS significantly increased from 0.85 (95% CI: 0.81, 0.88) to 0.91 (95% CI: 0.87, 0.93), 0.85 (95% CI: 0.80, 0.89) to 0.90 (95% CI: 0.85, 0.93) and 0.85 (95% CI: 0.82, 0.87) to 0.90 (95% CI: 0.88, 0.92) in the DC, VC and total cohorts respectively (P <.05 for all). The quantitative viscous parameters evaluated by US viscosity imaging contribute to breast cancer diagnosis when combined with BI-RADS. [ABSTRACT FROM AUTHOR]

White spot lesions (WSLs) represent a prominent pathology encountered during orthodontic treatment, originating from enamel demineralization induced by the accumulation of bacterial biofilms. The previously developed bioinspired enamel coating form of self-assembling antimicrobial peptide D-GL13K exhibited antimicrobial activity and enhanced acid impermeability, offering a potential solution to prevent demineralization. The primary aim of this investigation is to assess the in vivo anti-demineralization properties and biocompatibility of the D-GL13K coating. A rat model was developed to assess the antimicrobial enamel coating during fixed orthodontic treatment. The anti-demineralization efficacy attributed to the D-GL13K coating was evaluated by employing optical coherence tomography, Vickers microhardness testing, and scanning electron microscopy. The biocompatibility of the D-GL13K coating was investigated through histologic observations of vital organs and tissues using hematoxylin and eosin. The D-GL13K coating demonstrated significant anti-demineralization effects, evidenced by reduced demineralization depth analyzed through optical coherence tomography and enhanced Vickers hardness than in the noncoated control group, showcasing the coating's potential to protect teeth from WSLs. Scanning electron microscopy analysis further elucidated the diminished enamel damage observed in the group treated with D-GL13K. Importantly, histologic examination of vital organs and tissues using hematoxylin and eosin staining revealed no overt disparities between the D-GL13K coated group and the noncoated control group. The D-GL13K enamel coating demonstrated promising anti-demineralization and biocompatibility properties in a rat model, thereby suggesting its potential for averting WSLs after orthodontic interventions. Further research in human clinical settings is needed to evaluate the coating's long-term efficacy. • A rat model was developed to assess the demineralization in the presence of fixed orthodontic brackets. • The enamel coating exhibits excellent anti-demineralization properties and biocompatibility. • The coating provides a new strategy for preventing white spot lesions after orthodontic treatment. [ABSTRACT FROM AUTHOR]

The aim of this study was to establish and validate a Susceptibility-weighted imaging (SWI)-based predictive model for neonatal intracranial haemorrhage (ICH). A total of 1190 neonates suspected of ICH after cranial ultrasound screening in a tertiary hospital were retrospectively enrolled. The neonates were randomly divided into a training cohort and a internal validation cohort by a ratio of 7:3. Univariate analysis was used to analyze the correlation between risk factors and ICH, and the prediction model of neonatal ICH was established by multivariate logistic regression based on minimum Akaike information criterion (AIC). The nomogram was externally validated in another tertiary hospital of 91 neonates. The performance of the nomogram was evaluated in terms of discrimination by the area under the curve (AUC), calibration by the calibration curve and clinical net benefit by the decision curve analysis (DCA). Univariate analysis and min AIC-based multivariate logistic regression screened the following variables to establish a predictive model for neonatal ICH: Platelet count (PLT), gestational diabetes, mode of delivery, amniotic fluid contamination, 1-min Apgar score. The AUC was 0.715, 0.711, and 0.700 for the training cohort, internal validation cohort, and external validation cohort, respectively. The calibration curve showed a good correlation between the nomogram prediction and actual observation for ICH. DCA showed the nomogram was clinically useful. We developed and validated an easy-to-use nomogram to predict ICH for neonates. This model could support individualized risk assessment and healthcare. [ABSTRACT FROM AUTHOR]

[Display omitted] • Alox5 deficiency in neuron alleviates seizure activity and epileptogenesis. • Neuronal Alox5 deletion reverses neuron loss and astrogliosis. • The development of comorbidities in the chronic phase of epilepsy was alleviated by Alox5 deletion. • Anti-epileptic effect of neuronal Alox5 deletion may be linked with reducing glutamate. • The identification of Alox5 as a potential therapeutic target suggests its promising role in the management of epilepsy. Our previous work reveals a critical role of activation of neuronal Alox5 in exacerbating brain injury post seizures. However, whether neuronal Alox5 impacts the pathological process of epilepsy remains unknown. To prove the feasibility of neuron-specific deletion of Alox5 via CRISPR-Cas9 in the blockade of seizure onset and epileptic progression. Here, we employed a Clustered regularly interspaced short-palindromic repeat-associated proteins 9 system (CRISPR/Cas9) system delivered by adeno-associated virus (AAV) to specifically delete neuronal Alox5 gene in the hippocampus to explore its therapeutic potential in various epilepsy mouse models and possible mechanisms. Neuronal depletion of Alox5 was successfully achieved in the brain. AAV delivery of single guide RNA of Alox5 in hippocampus resulted in reducing seizure severity, delaying epileptic progression and improving epilepsy-associated neuropsychiatric comorbidities especially anxiety, cognitive deficit and autistic-like behaviors in pilocarpine- and kainic acid-induced temporal lobe epilepsy (TLE) models. In addition, neuronal Alox5 deletion also reversed neuron loss, neurodegeneration, astrogliosis and mossy fiber sprouting in TLE model. Moreover, a battery of tests including analysis of routine blood test, hepatic function, renal function, routine urine test and inflammatory factors demonstrated no noticeable toxic effect, suggesting that Alox5 deletion possesses the satisfactory biosafety. Mechanistically, the anti-epileptic effect of Alox5 deletion might be associated with reduction of glutamate level to restore excitatory/inhibitory balance by reducing CAMKII-mediated phosphorylation of Syn ISer603. Our findings showed the translational potential of AAV-mediated delivery of CRISPR-Cas9 system including neuronal Alox5 gene for an alternative promising therapeutic approach to treat epilepsy. [ABSTRACT FROM AUTHOR]

[Display omitted] • We introduced a novel chamber attention network (CAN) that utilizes the Grad-CAM technique to assess the relevance of different chambers in identifying PAH. • The attention vector generated by the chamber attention module provides a quantitative measure of the chambers' importance in PAH diagnosis, which aligns well with clinical knowledge and enhances the model's interpretability. • Our CAN model achieved outstanding performance on a large training-validation dataset consisting of 13912 individual subjects. • Evaluation on an external test dataset from a different hospital demonstrated the superior generalization ability of our CAN model. Accurate identification of pulmonary arterial hypertension (PAH) in primary care and rural areas can be a challenging task. However, recent advancements in computer vision offer the potential for automated systems to detect PAH from echocardiography. Our aim was to develop a precise and efficient diagnostic model for PAH tailored to the unique requirements of intelligent diagnosis, especially in challenging locales like high-altitude regions. We proposed the Chamber Attention Network (CAN) for PAH identification from echocardiographic images, trained on a dataset comprising 13,912 individual subjects. A convolutional neural network (CNN) for view classification was used to select the clinically relevant apical four chamber (A4C) and parasternal long axis (PLAX) views for PAH diagnosis. To assess the importance of different heart chambers in PAH diagnosis, we developed a novel Chamber Attention Module. The experimental results demonstrated that: 1) The substantial correspondence between our obtained chamber attention vector and clinical expertise suggested that our model was highly interpretable, potentially uncovering diagnostic insights overlooked by the clinical community. 2) The proposed CAN model exhibited superior image-level accuracy and faster convergence on the internal validation dataset compared to the other four models. Furthermore, our CAN model outperformed the others on the external test dataset, with image-level accuracies of 82.53% and 83.32% for A4C and PLAX, respectively. 3) Implementation of the voting strategy notably enhanced the positive predictive value (PPV) and negative predictive value (NPV) of individual-level classification results, enhancing the reliability of our classification outcomes. These findings indicate that CAN is a feasible technique for AI-assisted PAH diagnosis, providing new insights into cardiac structural changes observed in echocardiography. [ABSTRACT FROM AUTHOR]

• The research analyzes how coffee and caffeine intake are specifically related to the risk of COPD and overall lung function. • Smooth-fitting curves provide important insights into the dose-effect relationship between the exposures and the endpoints. • Potential cutting points have been identified, which can serve as personalized references for safe coffee or caffeine intake in COPD patients. The association between coffee and caffeine intake and the risk of COPD and lung function has not been thoroughly discussed in Americans, with subgroup and threshold effects remaining unclear. This study investigated the association between coffee and caffeine consumption and the risk of chronic obstructive pulmonary disease (COPD) as well as lung function utilizing data from the NHANES 2007–2012. We assessed the associations of coffee and caffeine consumption with the risk of COPD and lung function parameters, including FEV1 and FVC, adjusting for common demographic and disease characteristics in a cross-sectional analysis of NHANES data. A total of 9763 participants were included in the study, and 592 were diagnosed with COPD. Multivariate regression models revealed positive associations between coffee and caffeine consumption and the risk of COPD and lung function. Subgroup analyses stratified by sex, DM, hypertension status, and smoking habits identified potential effect modifiers as well as inflection points from threshold effect examinations. The results of this cross-sectional study indicated significant positive correlations between coffee and caffeine consumption and the risk of COPD. Additionally, positive correlations between exposure variables and FEV1 and FVC were detected. Among the stratification factors, smoking status exhibited the most potential for modifying effects. Future practices and research are needed to validate the results and explore the underlying mechanisms [ABSTRACT FROM AUTHOR]

The previous first-in-human study established the preliminary safety and effectiveness of the novel thin-strut iron bioresorbable scaffold (IBS). The current study aims to directly compare the imaging and physiological efficacy, and clinical outcomes of IBS with contemporary metallic drug-eluting stents (DES). A total of 518 patients were randomly allocated to treatment with IBS (257 patients) or metallic DES (261 patients) from 36 centers in China. The study is powered to test noninferiority of the IBS compared with the metallic everolimus-eluting stent in terms of the primary endpoint of in-segment late lumen loss at 2 years, and major secondary endpoints including 2-year quantitative flow ratio and cross-sectional mean flow area measured by optical coherence tomography (OCT) (limited to the OCT subgroup, 25 patients in each group). This will be the first powered randomized trial investigating the safety and efficacy of the novel thin-strut IBS compared to a contemporary metallic DES. The findings will provide valuable evidence for future research of this kind and the application of metallic bioresorbable scaffolds. [ABSTRACT FROM AUTHOR]

A novel single-sensor method for monitoring rotating blade vibration is proposed and utilized to identify vibration parameters under the non-stationary condition. By analyzing the pulse-signal waveform, the blade tip displacement and vibration velocity are extracted. Then, the motion equation under the non-stationary condition is further developed to provide a theoretical basis. Finally, the optimization technology is applied to extract vibration parameters. Compared with multiple-sensor methods, the proposed method has lower installation difficulty, less equipment cost, fewer sensors, and no strict sensor layout requirement. Numerical simulations and experiments are conducted to validate the effectiveness and robustness of the proposed method. The relative error in the natural frequency does not exceed 0.1 %. Additionally, errors in other parameters are less than 8 % in the experiment. • A novel single-sensor method is proposed to identify the vibration parameters of the blade under non-stationary condition. • A novel measurement approach is proposed, which is based on the blade tip vibration velocity (BTVV). • Dynamic characteristic of the non-stationary vibration is investigated by the theoretical analysis. And the formula expression of BTVV under non-stationary condition is first derived. • Simulations and the experiment are performed to validate the proposed method. [ABSTRACT FROM AUTHOR]

• It is innovative to introduce CEC during minitube manufacturing process. • The precision and performance of minitubes meet the requirements of use. • The effect of annealing on minitubes microstructure and degradation was studied. • This method is expected to promote the clinical application of Mg alloys stent. Due to its excellent biocompatibility and biodegradability, Mg and its alloys are considered to be promising materials for manufacturing of vascular sent. However, the manufacture of high-precision and high-performance Mg alloys minitubes is still a worldwide problem with a long manufacturing processing caused by the poor workability of Mg alloys. To solve this problem, the cyclic extrusion compression (CEC) was used to pretreat the billet by improving the workability of Mg alloys, finally shortening the manufacturing process. After CEC treatment, the size of grains and second phase particles of Mg alloys were dramatically refined to 3.2 µm and 0.3 µm, respectively. Only after three passes of cold drawing, the wall thickness of minitube was reduced from 0.200 mm to 0.135 mm and a length was more than 1000 mm. The error of wall thickness was measured to be less than 0.01 mm, implying a high dimensional accuracy. The yield strength (YS), ultimate tensile strength (UTS) and elongation of finished minitube were 220±10 MPa, 290±10 MPa and 22.0 ± 0.5%, respectively. In addition, annealing can improve mechanical property and corrosion resistance of minitubes by improving the homogeneity of the microstructure and enhancing the density of basal texture. [ABSTRACT FROM AUTHOR]

[Display omitted] β-Elemene (β-ELE), derived from Curcuma wenyujin , has anticancer effect on non-small cell lung cancer (NSCLC). However, the potential target and detail mechanism were still not clear. TFEB is the master regulator of lysosome biogenesis. Ferroptosis, a promising strategy for cancer therapy could be triggered via suppression on glutathione peroxidase 4 (GPX4). Weather TFEB-mediated lysosome degradation contributes to GPX4 decline and how β-ELE modulates on this process are not clear. To observe the action of β-ELE on TFEB, and the role of TFEB-mediated GPX4 degradation in β-ELE induced ferroptosis. Surface plasmon resonance (SPR) and molecular docking were applied to observe the binding affinity of β-ELE on TFEB. Activation of TFEB and lysosome were observed by immunofluorescence, western blot, flow cytometry and qPCR. Ferroptosis induced by β-ELE was observed via lipid ROS, a labile iron pool (LIP) assay and western blot. A549TFEB KO cells were established via CRISPR/Cas9. The regulation of TFEB on GPX4 and ferroptosis was observed in β-ELE treated A549WT and A549TFEB KO cells, which was further studied in orthotopic NOD/SCID mouse model. β-ELE can bind to TFEB, notably activate TFEB, lysosome and transcriptional increase on downstream gene GLA, MCOLN1, SLC26A11 involved in lysosome activity in EGFR wild-type NSCLC cells. β-ELE increased GPX4 ubiquitination and lysosomal localization, with the increase on lysosome degradation of GPX4. Furthermore, β-ELE induced ferroptosis, which could be promoted by TFEB overexpression or compromised by TFEB knockout. Genetic knockout or inactivation of TFEB compromised β-ELE induced lysosome degradation of GPX4, which was further demonstrated in orthotopic NSCLC NOD/SCID mice model. This study firstly demonstrated that TFEB promoted GPX4 lysosome degradation contributes to β-ELE induced ferroptosis in EGFR wild-type NSCLC, which gives a clue that TFEB mediated GPX4 degradation would be a novel strategy for ferroptosis induction and NSCLC therapy. [ABSTRACT FROM AUTHOR]

Previous studies have shown that plant-rich dietary patterns, such as the Mediterranean diet, are associated with longer telomeres. However, no association has been found between vegetarian diet and telomere length. We hypothesized that the quality of plant-based diets plays an important role in telomere length. Data were obtained from the National Health and Nutrition Examination Survey 1999–2002. Diet was assessed using a 24-h recall method. Plant-based diet quality was assessed using the overall plant-based diet index (PDI), healthy PDI (hPDI), and unhealthy PDI (uPDI). Telomere length was measured using quantitative PCR. Linear and ordinal logistic regression models were used to assess the association of PDIs with log-transformed telomere length and ordinal quintiles of telomere length in descending order, respectively. In both regression models, the overall PDI was not associated with telomere length. The hPDI was associated with longer telomere length [percentage change = 2.34%, 95% confidence interval (CI): 0.42%, 4.31%, P trend = 0.016; odds ratio (OR) = 0.81, 95% CI: 0.69, 0.95, P trend = 0.013]. However, uPDI was associated with shorter telomere length (percentage change = −3.17%, 95% CI: −5.65%, −0.62%, P trend = 0.017; OR = 1.25, 95% CI:1.03, 1.53, P trend = 0.014) and this inverse association was stronger in the non-Hispanic white population (P interaction = 0.001 in both regression models). A plant-based dietary pattern rich in healthy plant foods is associated with longer telomeres. However, plant-based dietary patterns rich in unhealthy plant-based foods are associated with shorter telomere lengths, especially in non-Hispanic white populations. [ABSTRACT FROM AUTHOR]

A wide variety of microorganisms have been closely linked to metal corrosion in the form of adherent surface biofilms. Biofilms allow the development and maintenance of locally corrosive environments and/or permit direct corrosion including pitting corrosion. The presence of numerous genetically distinct microorganisms in the oral environment poses a threat to the integrity and durability of the surface of metallic prostheses and implants used in routine dentistry. However, the association between oral microorganisms and specific corrosion mechanisms is not clear. It is of practical importance to understand how microbial corrosion occurs and the associated risks to metallic materials in the oral environment. This knowledge is also important for researchers and clinicians who are increasingly concerned about the biological activity of the released corrosion products. Accordingly, the main goal was to comprehensively review the current literature regarding oral microbiologically influenced corrosion (MIC) including characteristics of biofilms and of the oral environment, MIC mechanisms, corrosion behavior in the presence of oral microorganisms and potentially mitigating technologies. Findings included that oral MIC has been ascribed mostly to aggressive metabolites secreted during microbial metabolism (metabolite-mediated MIC). However, from a thermodynamic point of view, extracellular electron transfer mechanisms (EET-MIC) through pili or electron transfer compounds cannot be ruled out. Various MIC mitigating methods have been demonstrated to be effective in short term, but long term evaluations are necessary before clinical applications can be considered. Currently most in-vitro studies fail to simulate the complexity of intraoral physiological conditions which may either reduce or exacerbate corrosion risk, which must be addressed in future studies. A thorough analysis on literature regarding oral MIC (microbiologically influenced corrosion) of biomedical metallic materials has been carried out, including characteristics of oral environment, MIC mechanisms, corrosion behaviors in the presence of typical oral microorganisms and potential mitigating methods (materials design and surface design). There is currently a lack of mechanistic understanding of oral MIC which is very important not only to corrosion researchers but also to dentists and clinicians. This paper discusses the significance of biofilms from a biocorrosion perspective and summarizes several aspects of MIC mechanisms which could be caused by oral microorganisms. Oral MIC has been closely associated with not only the materials research but also the dental/clinical research fields in this work. [Display omitted] [ABSTRACT FROM AUTHOR]

Bacterial infections are a serious threat to wound healing and skin regeneration. In recent years, photothermal therapy (PTT) has become one of the most promising tools in the treatment of infectious diseases. However, wound dressings with photo-responsive properties are currently still limited by the difficulties of biosafety and thermal stability brought by the introduction of photosensitizers or photothermal agents. Therefore, how to improve the therapeutic efficiency and biosafety from material design is still a major challenge at present. In this study, the carboxymethyl chitosan (CMCS) and protocatechuic aldehyde (PA) hydrogels based on horseradish peroxidase (HRP) and hydrogen peroxide (H 2 O 2) enzymatic catalysis was developed. Therein, HRP and H 2 O 2 catalyzed cross-linking while polymerizing PA, which not only endowed the hydrogels with photothermal responsiveness but also with good biosafety through this enzyme-catalyzed green approach. Meanwhile, the hydrogels possessed highly efficient bacteriostatic ability with the assistance of near infrared (NIR). Moreover, the ultra-rapid gelation, strong tissue adhesion, high swelling ability, good antioxidant property and hemostatic property of the CMCS-PA hydrogels based on HRP/H 2 O 2 enzymatic catalysis were suitable for the treatment of skin wounds. Meanwhile, NIR-assistant CMCS-PA hydrogels based on HRP/H 2 O 2 enzymatic catalysis reduced inflammation, decreased bacterial infection, and promoted collagen deposition and angiogenesis, which showed remarkable therapeutic effects in a skin wound infection model. All results indicate that this green approach to introduce photothermal property by HRP-catalyzed PA polymerization endows the hydrogels with efficient photothermal conversion efficiency, suggesting that they are promising to provide new options for replacing photothermal agents and photosensitizers. In recent years, wound dressings with photo-responsive properties are currently still limited by the difficulties of biosafety and thermal stability brought by the introduction of agent photosensitizers or photothermal agents. In this study, the carboxymethyl chitosan and protocatechuic aldehyde hydrogels based on horseradish peroxidase and hydrogen peroxide enzymatic catalysis was developed. The photothermal properties of hydrogels were transformed from absent to present just by horseradish peroxidase-catalyzed protocatechuic aldehyde polymerization in a green approach. Meanwhile, the hydrogels possessed highly efficient bacteriostatic ability with the assistance of near infrared. The green approach of introducing photothermal properties from material design solves the biosafety challenge. Therefore, this study is expected to provide new options for alternative photothermal agents and photosensitizers. [Display omitted] [ABSTRACT FROM AUTHOR]

• Mg alloy sheet with circular texture was fabricated by multidirectional rolling. • Circular texture contributes to excellent ductility and weak in-plane anisotropy. • More active basal slips lead to higher ductility of circular texture for RD tension. • Similar soft grains result in weak in-plane yield anisotropy of circular texture. • Rarer tensile twins inhibit premature failure of circular texture for TD tension. Texture regulation is a prominent method to modify the mechanical properties and anisotropy of magnesium alloy. In this work, the Mg-1Al-0.3Ca-0.5Mn-0.2Gd (wt.%) alloy sheet with TD-tilted and circular texture was fabricated by unidirectional rolling (UR) and multidirectional rolling (MR) method, respectively. Unlike generating a strong in-plane mechanical anisotropy in conventional TD-tilted texture, the novel circular texture sample possessed a weak in-plane yield anisotropy. This can be rationalized by the similar proportion of soft grains with favorable orientation for basal slip and {10 1 ¯ 2} tensile twinning during the uniaxial tension of circular-texture sample along different directions. Moreover, compared with the TD-tilted texture, the circular texture improved the elongation to failure both along the rolling direction (RD) and transverse direction (TD). By quasi-in-situ EBSD-assisted slip trace analysis, higher activation of basal slip was observed in the circular-texture sample during RD tension, contributing to its excellent ductility. When loading along the TD, the TD-tilted texture promoted the activation of {10 1 ¯ 2} tensile twins significantly, thus providing nucleation sites for cracks and deteriorating the ductility. This research may shed new insights into the development of formable and ductile Mg alloy sheets by texture modification. [ABSTRACT FROM AUTHOR]

The formulation of recommendations is a crucial step in the development of clinical practice guidelines, which requires tools provided by the GRADE methodology. These tools include the evidence quality assessment tool, the evidence summary tool, and the evidence-to-decision (EtD) framework. Although there is a methodologically guided standard pathway for formulating recommendations in clinical practice guidelines, it remains unclear how to translate this theoretical pathway into the practical process for formulating recommendations and what the specific steps in this process entail. Therefore, this paper takes the World Federation of Acupuncture-Moxibustion Societies Clinical Practice Guidelines on Acupuncture and Moxibustion: Allergic Rhinitis as an example to detail the full process of formulating recommendations and summaries it into a three-step method. Step one : Collect original materials from different sources to create EtD table. Step two : Distribute and collect EtD table, and preliminarily gather the recommendation voting results. Step three : Organize "salami-slicing pattern" guideline development group consensus meeting to formulate recommendations. The three-step method for formulating recommendations in clinical practice guidelines fully utilizes the GRADE EtD table to provide guideline development group with decision-making foundation and reference from multiple dimensions, including the importance of clinical questions, balance of benefits and harms, quality of evidence, resource required, values and preferences, health equity, acceptability, and feasibility. This approach enhances the scientific and practical nature of guideline recommendations. This paper provides a standard operating procedure to formulate recommendations for the incoming clinical practice guidelines, which aims to establish a standard pathway for the formulation of acupuncture clinical practice guideline recommendations. [ABSTRACT FROM AUTHOR]

Urinary incontinence (UI) is common in women and affects the quality of life in female patients severely. But the clinical consideration and treatment are insufficient. Acupuncture and-moxibustion has been proposed as a potentially effective intervention for female UI. Hence, the World Federation of Acupuncture-moxibustion Societies (WFAS) have initiated a project to develop the clinical practice guideline (CPG) on acupuncture and moxibustion for female UI towards global acupuncture practitioners. The CPG was developed according to the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology, referring to the principles of the World Health Organization Handbook for Guideline Development. During the development of the CPG, the guideline development group (GDG) played an important role, which is composed of multi-national and multi-disciplinary experts. The clinical questions, recommendations and therapeutic protocols were all formulated by GDG using the modified Delphi method and basing on the results of the latest systematic review. This article focuses on the recommendations in the CPG. The CPG contains ten recommendations for ten clinical questions, including nine conditional recommendations for the intervention, one conditional recommendations for either the intervention or the comparison. The CPG also provides one conventional filiform needle therapy protocol, two deep puncturing stimulation on lumbosacral acupoints therapy protocols, and four moxibustion therapy protocols, extracted from the included clinical evidence of this CPG. [ABSTRACT FROM AUTHOR]

Clinical Practice Guideline on Acupuncture and Moxibustion: Allergic Rhinitis was revised and released by the Standards Working Committee of World Federation of Acupuncture-Moxibustion Societies (WFAS) on October 9, 2023. This is the first clinical practice guideline (CPG) on acupuncture and moxibustion for allergic rhinitis approved by an international academic organization, which provides evidence-based recommendations and the practical therapeutic protocols for acupuncture practitioners globally. This CPG was developed by following Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology, and the principles of the World Health Organization Handbook for Guideline Development. The members in the guideline development group (GDG) were from different countries, with different professions, and they played a critical role in the development of clinical questions, recommendations, and therapeutic protocols. Recommendations are the core of a CPG and the direct answers to clinical questions, due to which this article focuses on the recommendations of this CPG. The recommendations were developed by using the modified Delphi method and the GRADE grid rules, based on the updated systematic reviews of clinical evidence. A total of 15 recommendations for 15 clinical questions were developed in this CPG, including one strong recommendation for intervention based on high-quality evidence, three conditional recommendations for either the intervention or the comparison based on very low quality of evidence, and 11 conditional recommendations for the intervention based on very low quality of evidence. [ABSTRACT FROM AUTHOR]

• Hypertension and smoking are positively associated with an increased risk of ischemic stroke in Ph-negative MPNs patients. • Hypertension was the only independent risk factor for ischemic stroke in Ph-negative MPNs, regardless of JAK2V617F mutation. • It's crucial to assess the role of neutrophil/lymphocyte percentages as additional risk factors identified in our study. Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-negative MPNs) are linked with various complications, notably ischemic stroke. The study aims to identify risk factors for ischemic stroke in Ph-negative MPNs patients. Patients were categorized into two groups based on whether they had experienced ischemic stroke. Subsequently, an analysis of demographics, biochemical makers, and genetic mutations (JAK2V617F and CALR mutations), was conducted to identify potential associations with an elevated risk of ischemic stroke in individuals with Ph-negative MPNs. A total of 185 patients diagnosed with Ph-negative MPNs participated in the study, including 82 with essential thrombocythemia (ET), 78 with polycythemia vera (PV), and 25 with primary myelofibrosis (PMF). Among these, 57 patients (30.8 %) had a history of ischemic stroke. Independent risk factors associated with ischemic stroke in Ph-negative MPNs patients included hypertension (OR = 5.076) and smoking (OR = 5.426). Among ET patients, smoking (OR = 4.114) and an elevated percentage of neutrophils (OR = 1.080) were both positively correlated with ischemic stroke incidence. For PV patients, hypertension (OR = 4.647), smoking (OR = 6.065), and an increased percentage of lymphocytes (OR = 1.039) were independently associated with ischemic stroke. Regardless of the presence of the JAK2V617F mutation, hypertension was the sole positively and independently associated risk factor for ischemic stroke. The odds ratios for patients with the JAK2V617F mutation was 3.103, while for those without the mutation, it was 11.25. Hypertension was a more substantial factor associated with an increased incidence of ischemic stroke in Ph-negative MPNs patients. [ABSTRACT FROM AUTHOR]

[Display omitted] • Enteric fungi diversity was markedly altered in IIR injury. • Fungal colonization or mannan could alleviate IIR injury by decreasing GSDMD-mediated pyroptosis of IECs. • The protective role of fungi in IIR injury depends on macrophage involvement. • Single-fungal strains and mannan both alleviate GSDMD cleavage induced by reducing SAA1 expression of macrophages. Prophylactic antifungal therapy has been widely used for critical patients, but it has failed to improve patient prognosis and has become a hot topic. This may be related to disruption of fungal homeostasis, but the mechanism of fungi action is not clear. As a common pathway in critical patients, intestinal ischemia–reperfusion (IIR) injury is fatal and regulated by gut microbiota. However, the exact role of enteric fungi in IIR injury remains unclear. This is a clinical study that aims to provide new perspectives in clarifying the underlying mechanism of IIR injury and propose potential strategies that could be relevant for the prevention and treatment of IIR injury in the near future. ITS sequencing was performed to detect the changes in fungi before and after IIR injury. The composition of enteric fungi was altered by pretreatment with single-fungal strains, fluconazole and mannan, respectively. Intestinal morphology and function impairment were evaluated in the IIR injury mouse model. Intestinal epithelial MODE-K cells and macrophage RAW264.7 cells were cultured for in vitro tests. Fecal fungi diversity revealed the obvious alteration in IIR patients and mice, accompanied by intestinal epithelial barrier dysfunction. Fungal colonization and mannan supplementation could reverse intestinal morphology and function impairment that were exacerbated by fluconazole via inhibiting the expression of SAA1 from macrophages and decreasing pyroptosis of intestinal epithelial cells. Clodronate liposomes were used to deplete the number of macrophages, and it was demonstrated that the protective effect of mannan was dependent on macrophage involvement. This finding firstly validates that enteric fungi play a crucial role in IIR injury. Preventive antifungal treatment should consider damaging fungal balance. This study provides a novel clue to clarify the role of enteric fungi in maintaining intestinal homeostasis. [ABSTRACT FROM AUTHOR]

[Display omitted] • The iGG analysis has been proposed to utilize evolutionary information between the crop and several its relatives. • The evolution of CIPK and CBL genes have been characterized in seven species to prove the iGG method. • The divergent expression is important for keeping the stoichiometric balance of TaCBL-TaCIPK. • Our iGG analysis reveals a Triticeae-specific TaCIPK duplicate responding to drought. • Transgenic plants of TaCIPK17 -OE in tobacco and wheat showed higher resistance to drought. Reverse genetic studies conducted in the plant with a complex or polyploidy genome enriched with large gene families (like wheat) often meet challenges in identifying the key candidate genes related to important traits and prioritizing the genes for functional experiments. To overcome the above-mentioned challenges of reverse genetics, this work aims to establish an efficient multi-species strategy for genome-wide gene identification and prioritization of the key candidate genes. We established the integrative gene duplication and genome-wide analysis (iGG analysis) as a strategy for pinpointing key candidate genes deserving functional research. The iGG captures the evolution, and the expansion/contraction of large gene families across phylogeny-related species and integrates spatial–temporal expression information for gene function inference. Transgenic approaches were also employed to functional validation. As a proof-of-concept for the iGG analysis, we took the wheat calcineurin B-like protein-interacting protein kinases (CIPKs) family as an example. We identified CIPK s from seven monocot species, established the orthologous relationship of CIPK s between rice and wheat, and characterized Triticeae-specific CIPK duplicates (e.g. , CIPK4 and CIPK17). Integrated with our analysis of CBLs and CBL-CIPK interaction, we revealed that divergent expressions of TaCBL s and TaCIPK s could play an important role in keeping the stoichiometric balance of CBL-CIPK. Furthermore, we validated the function of TaCIPK17-A2 in the regulation of drought tolerance by using transgenic approaches. Overexpression of TaCIPK17 enhanced antioxidant capacity and improved drought tolerance in wheat. The iGG analysis leverages evolutionary and comparative genomics of crops with large genomes to rapidly highlight the duplicated genes potentially associated with speciation, domestication and/or particular traits that deserve reverse-genetic functional studies. Through the identification of Triticeae-specific TaCIPK17 duplicates and functional validation, we demonstrated the effectiveness of the iGG analysis and provided a new target gene for improving drought tolerance in wheat. [ABSTRACT FROM AUTHOR]

Approximately 10% of submucosal invasive (T1) colorectal cancers demonstrate extraintestinal lymph node metastasis, necessitating surgical intervention with lymph node dissection. The ability to identify T1b (submucosal invasion depth ≥ 1000 µm) as a risk factor for lymph node metastasis via pre-treatment endoscopy is crucial in guiding treatment strategies. Accurately distinguishing T1b from T1a (submucosal invasion depth < 1000 µm) or dysplasia remains a significant challenge for artificial intelligence (AI) systems, which require high and consistent diagnostic capabilities. Moreover, as endoscopic therapies like endoscopic full-thickness resection and endoscopic intermuscular dissection evolve, and the focus on reducing unnecessary surgeries intensifies, the initial management of T1 colorectal cancers via endoscopic treatment is anticipated to increase. Consequently, the development of highly accurate and reliable AI systems is essential, not only for pre-treatment depth assessment but also for post-treatment risk stratification of lymph node metastasis. While such AI diagnostic systems are still under development, significant advancements are expected in the near future to improve decision-making in T1 colorectal cancer management. [ABSTRACT FROM AUTHOR]

It has been revealed good nutritional status and no physical frailty, which are modifiable lifestyle factors, are linked to less cognitive decline and a lower risk of Alzheimer's disease (AD). We aimed to investigate the associations between nutritional status and physical frailty and plasma AD biomarkers, especially the Tau-associated biomarkers in older cognitively unimpaired (CU) adults with higher β-amyloid (Aβ) burden. The nutritional status and physical frailty were assessed via Mini-Nutritional Assessment Short-Form (MNA-SF) and Fried frailty index. The participants underwent the examination of plasma AD biomarkers and 18F-florbetapir PET scan as well as 18F-MK6240 PET in the validation cohort. Correlation and multiple linear regression analyses were used to investigate the associations between nutritional status and frailty and AD biomarkers. Two cohorts were included in our study. A total of 129 participants with Aβ-PET positive were enrolled in the development cohort. Multiple linear regression analysis showed MNA-SF scores, normal nutritional status, Fried frailty index scores, frailty and some domains of frailty including weight loss, maximal grip strength and exhaustion were associated with plasma p-Tau-181. Furthermore, weight loss, Fried frailty index scores and frailty were associated with higher Aβ-PET standard uptake value ratio. We further performed subgroup analyses stratified by age, sex and apolipoprotein E ε4 genotype to investigate the beneficial characteristics of nutrition and frailty in the special subgroups. Validation cohort contained 38 Aβ-PET positive participants. MNA-SF scores, normal nutritional status, Fried frailty index scores and frailty were associated with Tau burden evaluated by 18F-MK6240 PET Braak-like stages. Our data indicates that normal nutritional status and no physical frailty may be associated with expected trend of plasma AD biomarkers, especially less Tau pathology in older CU adults with Aβ deposition. Adjusting to these characteristics of nutrition and physical frailty may help reduce the risk of AD development. [ABSTRACT FROM AUTHOR]

• Due to widespread connectivity of the PCC to other regions, posterior cingulate epilepsy included polymorphic semiology of the seizures. • Behavioral arrest is the most common symptoms followed by automatisms and complex motor behaviors. Autonomic seizure was very rare in PCE. • Because of the extensive reciprocal connections between PCC and hippocampus, both hippocampal and PCC lesions may serve as seizure onset zones. • The intracerebral electrical stimulation mapping of PCC was induced vestibular responses were located in the dPCC and RSC and visual responses were located in the left RSC. Autonomic responses were elicited in vPCC and RSC. This study aimed to explore seizure semiology and the effects of intracerebral electrical stimulation on the human posterior cingulate cortex (PCC) using Stereoelectroencephalography (SEEG) to deepen our comprehension of posterior cingulate epilepsy (PCE). This study examined the characteristics of seizures through video documentation, by assessing the outcomes of intracranial electrical stimulation (iES) during SEEG. We further identified the connection between the observed semiology and precise anatomical locations within the PCC subregions where seizure onset zones (SOZ) were identified. Analysis was conducted on 59 seizures from 15 patients recorded via SEEG. Behavioural arrest emerged as the predominant manifestation across the PCC subregions. Where ictal activity extended to both the mesial and lateral temporal cortex, automatism was predominantly observed in seizures originating from the ventral PCC (vPCC). The retrosplenial cortex (RSC) is associated with complex motor behaviour, with seizure discharges spreading to the temporal lobe. Seizures originating from the PCC include axial tonic and autonomic seizures. Only one case of positive clinical seizures was documented. High frequencies of iES within the PCC induced various clinical responses, categorised as vestibular, visual, psychological, and autonomic, with vestibular reactions primarily occurring in the dorsal PCC (dPCC) and RSC, visual responses in the left RSC, and autonomic reactions in the vPCC and RSC. The manifestations of seizures in PCE vary according to the SOZ and the patterns of seizure propagation. The occurrence of seizures induced by iES is exceedingly rare, indicating that mapping of the PCC could pinpoint the primary sector of PCC. [ABSTRACT FROM AUTHOR]

The newer glucose-lowering drugs (GLDs), including Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i), have demonstrated superior cardio- and renal protective benefits compared to older GLDs in individuals with type 2 diabetes (T2D) at high risk for cardiovascular disease (CVD). This study examined the trends of the newer GLDs use in people with T2D who had a history of coronary heart disease or heart failure in the United States. We used 2005–2019 data from the Medical Expenditure Panel Survey (MEPS). Individuals with self-reported diabetes and CVD history were identified. There was a steady increase in the use of GLP-1RA only from 2008 (3 %) to 2019 (21 %) and SGLT2i only from 2014 (5 %) to 2019 (12 %). Individuals with dual use of both newer GLD classes increased from 0.62 % in 2015 to 6 % in 2019. The overall uptake of these two newer drugs in 2019 was less than 40 %. In other words, 60 % of individuals who can substantially benefit from these newer treatments did not use the treatments. The use of GLP-1RA and SGLT2i among individuals with T2D and a history of CVD was low and varied by insurance type. Policy-level interventions are needed to improve the use of these newer treatments further. We examined how newer glucose-lowering drugs are used among individuals with type 2 diabetes and at high risk for coronary heart disease or heart failure in the US. We found that 60 % of individuals who can substantially benefit from these newer treatments did not use the treatments due to the variation of insurance type. • The trends of SGLT2i and GLP-1RA in people with T2D who had a history of cardiovascular disease. • Subgroup analysis of SGLT2i and GLP-1RA utilization by health insurance type (Private, Medicare, or Medicaid). • Although the utilization of these newer GLDs has been increasing, their use among eligible populations remained low. [ABSTRACT FROM AUTHOR]