Molecular mechanisms and potential therapeutic targets in the pathogenesis of hypertension in visceral adipose tissue induced by a high-fat diet.

Background: Hypertension (HTN) presents a significant global public health challenge with diverse causative factors. The accumulation of visceral adipose tissue (VAT) due to a high-fat diet (HFD) is an independent risk factor for HTN. While various studies have explored pathogenic mechanisms, a comprehensive understanding of impact of VAT on blood pressure necessitates bioinformatics analysis. Methods: Datasets GSE214618 and GSE188336 were acquired from the Gene Expression Omnibus and analyzed to identify shared differentially expressed genes between HFD-VAT and HTN-VAT. Gene Ontology enrichment and protein-protein interaction analyses were conducted, leading to the identification of hub genes. We performed molecular validation of hub genes using RT-qPCR, Western-blotting and immunofluorescence staining. Furthermore, immune infiltration analysis using CIBERSORTx was performed. Results: This study indicated that the predominant characteristic of VAT in HTN was related to energy metabolism. The red functional module was enriched in pathways associated with mitochondrial oxidative respiration and ATP metabolism processes. Spp1, Postn, and Gpnmb in VAT were identified as hub genes on the pathogenic mechanism of HTN. Proteins encoded by these hub genes were closely associated with the target organs-specifically, the resistance artery, aorta, and heart tissue. After treatment with empagliflozin, there was a tendency for Spp1, Postn, and Gpnmb to decrease in VAT. Immune infiltration analysis confirmed that inflammation and immune response may not be the main mechanisms by which visceral adiposity contributes to HTN. Conclusions: Our study pinpointed the crucial causative factor of HTN in VAT following HFD. Spp1, Postn, and Gpnmb in VAT acted as hub genes that promote elevated blood pressure and can be targets for HTN treatment. These findings contributed to therapeutic strategies and prognostic markers for HTN.

TRPV1 signaling of perirenal adipose tissue promotes DOCA-Salt-induced hypertension and kidney injury.

BACKGROUND: Denervation of renal or perirenal adipose tissue (PRAT) can reduce arterial blood pressure in various hypertensive experimental models. Trpv1 (transient receptor potential vanillin 1) channel is highly expressed in the renal sensory nerves and the dorsal root ganglias (DRGs) projected by PRAT. However, it is currently unclear whether Trpv1 in DRGs projected from PRAT can regulate renal hypertension. METHODS: We used resintoxin (RTX) to block the afferent sensory nerves of rat PRAT. We also constructed Trpv1-/- mice and Trpv1+/- mice or used the injection of AAV2-retro-shTrpv1 to detect the effects of Trpv1 knockout or knockdown of PRAT-projected DRGs on deoxycorticosterone acetate (DOCA)-Salt-induced hypertension and kidney injury. RESULTS: Blocking the afferent sensory nerves of PRAT with RTX can alleviate DOCA-Salt-induced hypertension and renal injury in rats. And this blockade reduces the expression of Trpv1 in the DRGs projected by PRAT. Injecting AAV2-retro-shTrpv1 into the PRAT of DOCA-Salt mice also achieved the same therapeutic effect. However, DOCA-Salt-induced hypertension and renal injury can be treated in Trpv1+/- mice but not alleviated or even worsened in Trpv1-/- mice, possibly because of compensatory increase of Trpv5 in DRG of Trpv1-/- mice. CONCLUSION: Reducing, rather than eliminating, Trpv1 in DRG from PRAT-projection can reduce blood pressure and kidney damage in DOCA-Salt in rats or mice. Trpv1 in PRAT-DRGs may serve as a therapeutic target for salt-sensitive hypertension and its renal complications.

The efficacy and safety of continuous intravenous infusion of rh-endostatin combined with platinum-based doublet chemotherapy for advanced non-small-cell lung cancer.

BACKGROUND: Platinum-based doublet chemotherapy is commonly used in the treatment of non-small cell lung cancer (NSCLC). A growing body of evidence indicates that incorporating antiangiogenic agents into platinum-based chemotherapy may enhance the survival outcomes for NSCLC patients. However, the optimal administration protocol for intravenous recombinant human endostatin (rh-endostatin), an antiangiogenic agent, remains uncertain at present. AIM: This study aims to investigate the efficacy and safety of 5-d continuous intravenous infusion of rh-endostatin in combination with chemotherapy for patients with advanced NSCLC. The predictive biomarkers for this treatment regimen were further probed. METHODS: This prospective, single-arm multicenter study enrolled a total of 48 patients with advanced NSCLC who were histologically or cytologically confirmed but had not received any prior treatment from January 2021 to December 2022. Prior to the chemotherapy, these patients received a continuous intravenous infusion of rh-endostatin (210 mg) over a period of 120 h, using an infusion pump. The chemotherapy regimen included a combination of platinum with either pemetrexed or paclitaxel, given in 21-day cycles. The primary endpoint of the study was median progression-free survival (mPFS), and the secondary endpoints included median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), and assessment of adverse events (AEs). RESULTS: The mPFS was 6.5 months (95% confidence interval (CI): 3.8-9.1 m) while the mOS was 12.3 months (95% CI: 7.6-18.5 m). The ORR and DCR was 52.1% and 75.0%, respectively. Leukopenia (52.1%), anemia (33.3%), and thrombocytopenia (20.8%) were the most common adverse effects and these toxicities were deemed acceptable and manageable. In addition, a correlation was noted between elevated serum carcinoembryonic antigen (CEA) levels and decreased PFS and OS. CONCLUSIONS: The incorporation of a 5-day continuous intravenous infusion of rh-endostatin into platinum-based doublet chemotherapy has demonstrated both safety and efficacy in the treatment of advanced NSCLC. Furthermore, the baseline serum levels of CEA may potentially function as a predictor for the efficacy of rh-endostatin when combined with chemotherapy in NSCLC patients. CLINICALTRIALS: GOV: NCT05574998.

Evaluation of osteogenic properties of a novel injectable bone-repair material containing strontium in vitro and in vivo.

Objective: This study aims to develop and evaluate the biocompatibility and osteogenic potential of a novel injectable strontium-doped hydroxyapatite bone-repair material. Methods: The properties of strontium-doped hydroxyapatite/chitosan (Sr-HA/CS), hydroxyapatite/chitosan (HA/CS) and calcium phosphate/chitosan (CAP/CS) were assessed following their preparation via physical cross-linking and a one-step simplified method. Petri dishes containing Escherichia coli and Staphylococcus epidermidis were inoculated with the material for in vitro investigations. The material was also co-cultured with stem cells derived from human exfoliated deciduous teeth (SHEDs), to assess the morphology and proliferation capability of the SHEDs, Calcein-AM staining and the Cell Counting Kit-8 assay were employed. Osteogenic differentiation of SHEDs was determined using alkaline phosphatase (ALP) staining and Alizarin Red staining. For in vivo studies, Sr-HA/CS was implanted into the muscle pouch of mice and in a rat model of ovariectomy-induced femoral defects. Hematoxylin-eosin (HE) staining was performed to determine the extent of bone formation and defect healing. The formation of new bone was determined using Masson's trichrome staining. The osteogenic mechanism of the material was investigated using Tartrate-resistant acid phosphatase (TRAP) staining and immunohistochemical studies. Results: X-ray diffraction (XRD) and energy-dispersive spectroscopy (EDS) showed that strontium was successfully doped into HA. The Sr-HA/CS material can be uniformly squeezed using a syringe with a 13% swelling rate. Sr-HA/CS had a significant antibacterial effect against both E. coli and S. epidermidis (p < 0.05), with a stronger effect observed against E. coli. The Sr-HA/CS significantly improved cell proliferation and cell viability in vitro studies (p < 0.05). Compared to CAP/CS and CS, Sr-HA/CS generated a substantially greater new bone area during osteoinduction experiments (p < 0.05, p < 0.001). The Sr-HA/CS material demonstrated a significantly higher rate of bone repair in the bone defeat studies compared to the CAP/CS and CS materials (p < 0.01). The OCN-positive area and TRAP-positive cells in Sr-HA/CS were greater than those in control groups (p < 0.05). Conclusion: A novel injectable strontium-doped HA bone-repair material with good antibacterial properties, biocompatibility, and osteoinductivity was successfully prepared.

The prognostic value and immunological role of MVP in pan-cancer study.

Major Vault Protein (MVP) has emerged as a potential prognostic and immunological biomarker in various cancer types. This pan-cancer study aimed to investigate expression of MVP and its correlation with clinical outcomes and immune infiltration across diverse cancer types. We conducted an analysis of extensive transcriptomic and clinical data from publicly available databases. Our findings unveiled a significant association between MVP expression and cancer progression, with higher expression levels predicting poorer overall survival in multiple cancer types. Importantly, MVP expression demonstrated a close relationship with immune infiltration in the tumor microenvironment, showing that higher expression levels were associated with increased immune cell infiltration. We further validated expression of MVP and function in cancer cell lines A549 and AGS. These compelling results suggest that MVP holds promise as a valuable biomarker for prognostic assessment and the development of immunotherapeutic strategies across various cancer types. Consequently, targeting MVP may offer a compelling therapeutic approach in the treatment of human cancers.

Dose-Dependent Association Between Body Mass Index and Mental Health and Changes Over Time.

Importance: Overweight and obesity affect 340 million adolescents worldwide and constitute a risk factor for poor mental health. Understanding the association between body mass index (BMI) and mental health in adolescents may help to address rising mental health issues; however, existing studies lack comprehensive evaluations spanning diverse countries and periods. Objective: To estimate the association between BMI and mental health and examine changes over time from 2002 to 2018. Design, Setting, and Participants: This was a repeated multicountry cross-sectional study conducted between 2002 and 2018 and utilizing data from the Health Behaviour in School-aged Children (HBSC) survey in Europe and North America. The study population consisted of more than 1 million adolescents aged 11 to 15 years, with all surveyed children included in the analysis. Data were analyzed from October 2022 to March 2023. Main Outcomes and Measures: Mental health difficulties were measured by an 8-item scale for psychological concerns, scoring from 0 to 32, where a higher score reflects greater psychosomatic issues. BMI was calculated using weight divided by height squared and adjusted for age and sex. Data were fitted by multilevel generalized additive model. Confounders included sex, living with parents, sibling presence, academic pressure, the experience of being bullied, family affluence, screen time, and physical activity. Results: Our analysis of 1 036 869 adolescents surveyed from 2002 to 2018, with a mean (SD) age of 13.55 (1.64) years and comprising 527 585 girls (50.9%), revealed a consistent U-shaped association between BMI and mental health. After accounting for confounders, adolescents with low body mass and overweight or obesity had increased psychosomatic symptoms compared to those with healthy weight (unstandardized ß, 0.14; 95% CI, 0.08 to 0.19; unstandardized ß, 0.27; 95% CI, 0.24 to 0.30; and unstandardized ß, 0.62; 95% CI, 0.56 to 0.67, respectively), while adolescents with underweight had fewer symptoms (unstandardized ß, -0.18; 95% CI, -0.22 to -0.15). This association was observed across different years, sex, and grade, indicating a broad relevance to adolescent mental health. Compared to 2002, psychosomatic concerns increased significantly in 2006 (unstandardized ß, 0.19; 95% CI, 0.11 to 0.26), 2010 (unstandardized ß, 0.14; 95% CI, 0.07 to 0.22), 2014 (unstandardized ß, 0.48; 95% CI, 0.40 to 0.56), and 2018 (unstandardized ß, 0.82; 95% CI, 0.74 to 0.89). Girls reported significantly higher psychosomatic concerns than boys (unstandardized ß, 2.27; 95% CI, 2.25 to 2.30). Compared to primary school, psychosomatic concerns rose significantly in middle school (unstandardized ß, 1.15; 95% CI, 1.12 to 1.18) and in high school (unstandardized ß, 2.12; 95% CI, 2.09 to 2.15). Conclusions and Relevance: Our study revealed a U-shaped association between adolescent BMI and mental health, which was consistent across sex and grades and became stronger over time. These insights emphasize the need for targeted interventions addressing body image and mental health, and call for further research into underlying mechanisms.

In-beam PET monitoring of proton therapy: a method for filtering prompt radiation events.

OBJECTIVE: In-beam Positron Emission Tomography (PET) is a promising technology for real-time monitoring of proton therapy. Random coincidences between prompt radiation events and positron annihilation photon pairs can deteriorate imaging quality during beam-on operation. This study aimed to improve the PET image quality by filtering out the prompt radiation events. APPROACH: We investigated a prompt radiation event filtering method based on the accelerator radio frequency (RF) phase and assessed its performance using various prompt gamma energy thresholds. An in-beam PET prototype was used to acquire the data when the 70 MeV proton beam irradiated a water phantom and a mouse. The signal-to-background ratio indicator was utilized to evaluate the quality of the PET reconstruction image. MAIN RESULTS: The selection of the prompt gamma energy threshold will affect the quality of the reconstructed image. Using the optimal energy threshold of 580 keV can obtain a signal-to-background ratio of 1.6 times for the water phantom radiation experiment and 2.0 times for the mouse radiation experiment compared to those without background removal, respectively. SIGNIFICANCE: Our results show that using this optimal threshold can reduce the prompt radiation events, enhancing the signal-to-background ratio of the reconstructed image. This advancement contributes to more accurate real-time range verification in subsequent steps.

Unraveling Stoichiometry Effect in Nickel-Tungsten Alloys for Efficient Hydrogen Oxidation Catalysis in Alkaline Electrolytes.

Anion-exchange membrane fuel cells provide the possibility to use platinum group metal-free catalysts, but the anodic hydrogen oxidation reaction (HOR) suffers from sluggish kinetics and its source is still debated. Here, over nickel-tungsten (Ni-W) alloy catalysts, we show that the Ni:W ratio greatly governs the HOR performance in alkaline electrolyte. Experimental and theoretical studies unravel that alloying with W can tune the unpaired electrons in Ni, tailoring the potential of zero charge and the catalytic surface to favor hydroxyl adsorption (OHad). The OHad species coordinately interact with potassium (K+) ions, which break the K+ solvation sheath to leave free water molecules, yielding an improved connectivity of hydrogen-bond networks. Consequently, the optimal Ni17W3 alloy exhibits alkaline HOR activity superior to the state-of-the-art platinum on carbon (Pt/C) catalyst and operates steadily with negligible decay after 10,000 cycles. Our findings offer new understandings of alloyed HOR catalysts and will guide rational design of next-generation catalysts for fuel cells.

Recent progress in multifunctional, reconfigurable, integrated liquid metal-based stretchable sensors and standalone systems.

Possessing a unique combination of properties that are traditionally contradictory in other natural or synthetical materials, Ga-based liquid metals (LMs) exhibit low mechanical stiffness and flowability like a liquid, with good electrical and thermal conductivity like metal, as well as good biocompatibility and room-temperature phase transformation. These remarkable properties have paved the way for the development of novel reconfigurable or stretchable electronics and devices. Despite these outstanding properties, the easy oxidation, high surface tension, and low rheological viscosity of LMs have presented formidable challenges in high-resolution patterning. To address this challenge, various surface modifications or additives have been employed to tailor the oxidation state, viscosity, and patterning capability of LMs. One effective approach for LM patterning is breaking down LMs into microparticles known as liquid metal particles (LMPs). This facilitates LM patterning using conventional techniques such as stencil, screening, or inkjet printing. Judiciously formulated photo-curable LMP inks or the introduction of an adhesive seed layer combined with a modified lift-off process further provide the micrometer-level LM patterns. Incorporating porous and adhesive substrates in LM-based electronics allows direct interfacing with the skin for robust and long-term monitoring of physiological signals. Combined with self-healing polymers in the form of substrates or composites, LM-based electronics can provide mechanical-robust devices to heal after damage for working in harsh environments. This review provides the latest advances in LM-based composites, fabrication methods, and their novel and unique applications in stretchable or reconfigurable sensors and resulting integrated systems. It is believed that the advancements in LM-based material preparation and high-resolution techniques have opened up opportunities for customized designs of LM-based stretchable sensors, as well as multifunctional, reconfigurable, highly integrated, and even standalone systems.

Nanobubbles improve peroxymonosulfate-based advanced oxidation: High efficiency, low toxicity/cost, and novel collaborative mechanism.

Cl- activated peroxymonosulfate (PMS) oxidation technology can effectively degrade pollutants, but the generation of chlorinated disinfection byproducts (DBPs) limits the application of this technology in water treatment. In this study, a method of nanobubbles (NBs) synergistic Cl-/PMS system was designed to try to improve this technology. The results showed the synergistic effects of NBs/Cl-/PMS were significant and universal while its upgrade rate was from 12.89% to 34.97%. Moreover, the synergistic effects can be further improved by increasing the concentration and Zeta potential of NBs. The main synergistic effects of NBs/Cl-/PMS system were due to the electrostatic attraction of negatively charged NBs to Na+ from NaCl, K+ from PMS, and H+ from phenol, which acted as a "bridge" between Cl- and HSO5- as well as phenol and Cl-/HSO5-, increasing active substance concentration. In addition, the addition of NBs completely changed the oxidation system of Cl-/PMS from one that increases environmental toxicity to one that reduces it. The reason was that the electrostatic attraction of NBs changed the active sites and degradation pathway of phenol, greatly reducing the production of highly toxic DBPs. This study developed a novel environmentally friendly oxidation technology, which provides an effective strategy to reduce the generation of DBPs in the Cl-/PMS system.

IGF2BP3 modified GLI2 transcriptionally regulates SYVN1 and facilitates sepsis liver injury through autophagy.

Autophagy enhancement in septic liver injury can play a protective role. Nerveless, the mechanism of autophagy-mediated septic liver injury needs further investigation. Our study demonstrated that in septic condition, GLI Family Zinc Finger 2 (GLI2) was elevated, whereas peroxisome-proliferator-activated receptor α (PPARα) was downregulated. Suppressing GLI2 or synovialapoptosis inhibitor 1 (SYVN1) in LPS-exposed cells increased PPARα levels, enhanced cell viability and autophagy, while inhibiting apoptosis. LPS enhanced the GLI2-SYVN1 promoter binding. SYVN1 fostered ubiquitin-mediated degradation of PPARα. IGF2BP3 stabilized GLI2 mRNA by targeting its m6A site. Silencing IGF2BP3 led to decreased GLI2 and SYVN1 but increased PPARα levels, promoting cell survival and autophagy, while repressing apoptosis. This was counteracted by SYVN1 overexpression. In cecal ligation and puncture mice, IGF2BP3, SYVN1, or GLI2 knockdown ameliorated liver damage and augmented autophagy. In summary, IGF2BP3 enhanced GLI2 stability, overexpressed GLI2 subsequent promoted SYVN1 levels by interacting with its promoter, leading to ubiquitinated degradation of PPARα, thereby inhibiting PPARα-mediated autophagy and then exacerbating liver injury in sepsis.

Opportunistic smoking cessation interventions for people accessing financial support settings: A scoping review.

AIM: The aim of this work was to systematically scope the evidence on opportunistic tobacco smoking cessation interventions for people accessing financial support settings. METHODS: We searched MEDLINE, Embase, PsycINFO and the Cochrane Tobacco Addiction Group specialized register to 21 March 2023. We duplicate screened 20% of titles/abstracts and all full texts. We included primary studies investigating smoking cessation interventions delivered opportunistically to people who smoked tobacco, within settings offering support for problems caused by financial hardship, for example homeless support services, social housing and food banks. Data were charted by one reviewer, checked by another and narratively synthesized. RESULTS: We included 25 studies conducted in a range of financial support settings using qualitative (e.g. interviews and focus groups) and quantitative (e.g. randomized controlled trials, surveys and single arm intervention studies) methodologies. Evidence on the acceptability and feasibility of opportunistic smoking cessation advice was investigated among both clients and providers. Approximately 90% of service providers supported such interventions; however, lack of resources, staff training and a belief that tobacco smoking reduced illicit substance use were perceived barriers. Clients welcomed being asked about smoking and offered assistance to quit and expressed interest in interventions including the provision of nicotine replacement therapy, e-cigarettes and incentives to quit smoking. Six studies investigated the comparative effectiveness of opportunistic smoking cessation interventions on quitting success, with five comparing more to less intensive interventions, with mixed results. CONCLUSIONS: Most studies investigating opportunistic smoking cessation interventions in financial support settings have not measured their effectiveness. Where they have, settings, populations, interventions and findings have varied. There is more evidence investigating acceptability, with promising results.

High-integrity Pueraria montana var. lobata genome and population analysis revealed the genetic diversity of Pueraria genus.

Pueraria montana var. lobata (P. lobata) is a traditional medicinal plant belonging to the Pueraria genus of Fabaceae family. Pueraria montana var. thomsonii (P. thomsonii) and Pueraria montana var. montana (P. montana) are its related species. However, evolutionary history of the Pueraria genus is still largely unknown. Here, a high-integrity, chromosome-level genome of P. lobata and an improved genome of P. thomsonii were reported. It found evidence for an ancient whole-genome triplication and a recent whole-genome duplication shared with Fabaceae in three Pueraria species. Population genomics of 121 Pueraria accessions demonstrated that P. lobata populations had substantially higher genetic diversity, and P. thomsonii was probably derived from P. lobata by domestication as a subspecies. Selection sweep analysis identified candidate genes in P. thomsonii populations associated with the synthesis of auxin and gibberellin, which potentially play a role in the expansion and starch accumulation of tubers in P. thomsonii. Overall, the findings provide new insights into the evolutionary and domestication history of the Pueraria genome and offer a valuable genomic resource for the genetic improvement of these species.

Direct Laser Processing and Functionalizing PI/PDMS Composites for an On-Demand, Programmable, Recyclable Device Platform.

Skin-interfaced high-sensitive biosensing systems to detect electrophysiological and biochemical signals have shown great potential in personal health monitoring and disease management. However, the integration of 3D porous nanostructures for improved sensitivity and various functional composites for signal transduction/processing/transmission often relies on different materials and complex fabrication processes, leading to weak interfaces prone to failure upon fatigue or mechanical deformations. The integrated system also needs additional adhesive to strongly conform to the human skin, which can also cause irritation, alignment issues, and motion artifacts. This work introduces a skin-attachable, reprogrammable, multifunctional, adhesive device patch fabricated by simple and low-cost laser scribing of an adhesive composite with polyimide powders and amine-based ethoxylated polyethylenimine dispersed in the silicone elastomer. The obtained laser-induced graphene in the adhesive composite can be further selectively functionalized with conductive nanomaterials or enzymes for enhanced electrical conductivity or selective sensing of various sweat biomarkers. The possible combination of the sensors for real-time biofluid analysis and electrophysiological signal monitoring with RF energy harvesting and communication promises a standalone stretchable adhesive device platform based on the same material system and fabrication process.

Mitigating the Poisoning Effect of Formate during CO2 Hydrogenation to Methanol over Co-Containing Dual-Atom Oxide Catalysts.

During the hydrogenation of CO2 to methanol over mixed-oxide catalysts, the strong adsorption of CO2 and formate poses a barrier for H2 dissociation, limiting methanol selectivity and productivity. Here we show that by using Co-containing dual-atom oxide catalysts, the poisoning effect can be countered by separating the site for H2 dissociation and the adsorption of intermediates. We synthesized a Co- and In-doped ZrO2 catalyst (Co-In-ZrO2) containing atomically dispersed Co and In species. Catalyst characterization showed that Co and In atoms were atomically dispersed and were in proximity to each other owing to a random distribution. During the CO2 hydrogenation reaction, the Co atom was responsible for the adsorption of CO2 and formate species, while the nearby In atoms promoted the hydrogenation of adsorbed intermediates. The cooperative effect increased the methanol selectivity to 86% over the dual-atom catalyst, and methanol productivity increased 2-fold in comparison to single-atom catalysts. This cooperative effect was extended to Co-Zn and Co-Ga doped ZrO2 catalysts. This work presents a different approach to designing mixed-oxide catalysts for CO2 hydrogenation based on the preferential adsorption of substrates and intermediates instead of promoting H2 dissociation to mitigate the poisonous effects of substrates and intermediates.

Resistant Starch from Purple Sweet Potatoes Alleviates Dextran Sulfate Sodium-Induced Colitis through Modulating the Homeostasis of the Gut Microbiota.

Ulcerative colitis (UC) is a complicated inflammatory disease with a continually growing incidence. In this study, resistant starch was obtained from purple sweet potato (PSPRS) by the enzymatic isolation method. Then, the structural properties of PSPRS and its protective function in dextran sulfate sodium (DSS)-induced colitis were investigated. The structural characterization results revealed that the crystallinity of PSPRS changed from CA-type to A-type, and the lamellar structure was totally destroyed during enzymatic hydrolysis. Compared to DSS-induced colitis mice, PSPRS administration significantly improved the pathological phenotype and colon inflammation in a dose-dependent manner. ELISA results indicated that DSS-induced colitis mice administered with PSPRS showed higher IL-10 and IgA levels but lower TNF-α, IL-1ß, and IL-6 levels. Meanwhile, high doses (300 mg/kg) of PSPRS significantly increased the production of acetate, propionate, and butyrate. 16S rDNA high-throughput sequencing results showed that the ratio of Firmicutes to Bacteroidetes and the potential probiotic bacteria levels were notably increased in the PSPRS treatment group, such as Lactobacillus, Alloprevotella, Lachnospiraceae_NK4A136_group, and Bifidobacterium. Simultaneously, harmful bacteria like Bacteroides, Staphylococcus, and Akkermansia were significantly inhibited by the administration of a high dose of PSPRS (p < 0.05). Therefore, PSPRS has the potential to be a functional food for promoting intestinal health and alleviating UC.

Association between dietary folate intake and severe abdominal aorta calcification in adults: A cross-sectional analysis of the national health and nutrition examination survey.

BACKGROUND: Prior studies have established a connection between folate intake and cardiovascular disease (CVD). Abdominal aortic calcification (AAC) has been introduced as a good predictor of CVD events, but no previous study has investigated the relationship between dietary folate intake and severe AAC. Therefore, the study aims to explore the association between dietary folate intake and severe AAC in the United States (US) middle-aged and elderly population. METHODS: This study employed cross-sectional data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) to examine the relationship between dietary folate intake and severe AAC. Two 24-h dietary recall interviews were conducted to assess dietary folate intake and its sources, while a DXA scan was used to determine the AAC score. To analyze the association between dietary folate intake and severe AAC, a multivariable logistic regression model was applied, and a subgroup analysis was performed. RESULTS: Our analysis utilized data from 2640 participants aged 40 years and above, including 288 individuals diagnosed with severe AAC. After adjusting for confounding factors, we observed an inverted L-shaped association between folate intake and severe AAC. Upon further adjustment for specific confounding factors and covariates, the multivariable-adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the second, third, and fourth quartiles of folate intake, using the first quartile as the reference, were as follows: 1.24 (0.86-1.79), 0.86 (0.58-1.27), and 0.63 (0.41-0.97), respectively. Subgroup analysis results were consistent with the logistic regression models, indicating concordant findings. Moreover, no significant interaction was observed in the subgroup analyses. CONCLUSIONS: The study findings suggest an inverted L-shaped association between dietary folate intake and severe AAC. However, additional prospective investigations are necessary to explore the impact of dietary folate intake on severe AAC in patients.

Glucose controls lipolysis through Golgi PtdIns4P-mediated regulation of ATGL.

Metabolic crosstalk of the major nutrients glucose, amino acids and fatty acids (FAs) ensures systemic metabolic homeostasis. The coordination between the supply of glucose and FAs to meet various physiological demands is especially important as improper nutrient levels lead to metabolic disorders, such as diabetes and metabolic dysfunction-associated steatohepatitis (MASH). In response to the oscillations in blood glucose levels, lipolysis is thought to be mainly regulated hormonally to control FA liberation from lipid droplets by insulin, catecholamine and glucagon. However, whether general cell-intrinsic mechanisms exist to directly modulate lipolysis via glucose sensing remains largely unknown. Here we report the identification of such an intrinsic mechanism, which involves Golgi PtdIns4P-mediated regulation of adipose triglyceride lipase (ATGL)-driven lipolysis via intracellular glucose sensing. Mechanistically, depletion of intracellular glucose results in lower Golgi PtdIns4P levels, and thus reduced assembly of the E3 ligase complex CUL7FBXW8 in the Golgi apparatus. Decreased levels of the E3 ligase complex lead to reduced polyubiquitylation of ATGL in the Golgi and enhancement of ATGL-driven lipolysis. This cell-intrinsic mechanism regulates both the pool of intracellular FAs and their extracellular release to meet physiological demands during fasting and glucose deprivation. Moreover, genetic and pharmacological manipulation of the Golgi PtdIns4P-CUL7FBXW8-ATGL axis in mouse models of simple hepatic steatosis and MASH, as well as during ex vivo perfusion of a human steatotic liver graft leads to the amelioration of steatosis, suggesting that this pathway might be a promising target for metabolic dysfunction-associated steatotic liver disease and possibly MASH.

Learning long- and short-term dependencies for improving drug-target binding affinity prediction using transformer and edge contraction pooling.

The accurate identification of drug-target affinity (DTA) is crucial for advancements in drug discovery and development. Many deep learning-based approaches have been devised to predict drug-target binding affinity accurately, exhibiting notable improvements in performance. However, the existing prediction methods often fall short of capturing the global features of proteins. In this study, we proposed a novel model called ETransDTA, specifically designed for predicting drug-target binding affinity. ETransDTA combines convolutional layers and transformer, allowing for the simultaneous extraction of both global and local features of target proteins. Additionally, we have integrated a new graph pooling mechanism into the topology adaptive graph convolutional network (TAGCN) to enhance its capacity for learning feature representations of chemical compounds. The proposed ETransDTA model has been evaluated using the Davis and Kinase Inhibitor BioActivity (KIBA) datasets, consistently outperforming other baseline methods. The evaluation results on the KIBA dataset reveal that our model achieves the lowest mean square error (MSE) of 0.125, representing a 0.6% reduction compared to the lowest-performing baseline method. Furthermore, the incorporation of queries, keys and values produced by the stacked convolutional neural network (CNN) enables our model to better integrate the local and global context of protein representation, leading to further improvements in the accuracy of DTA prediction.

Retroperitoneal Laparoscopic Debridement and Drainage for Pancreatic Abscess.

In patients with severe necrotizing pancreatitis, pancreatic necrosis and secondary infection of surrounding tissues can quickly spread to the whole retroperitoneal space. Treatment of pancreatic abscess complicating necrotizing pancreatitis is difficult and has a high mortality rate. The well-accepted treatment strategy is early debridement of necrotic tissues, drainage, and postoperative continuous retroperitoneal lavage. However, traditional open surgery has several disadvantages, such as severe trauma, interference with abdominal organs, a high rate of postoperative infection and adhesion, and hardness with repeated debridement. The retroperitoneal laparoscopic approach has the advantages of minimal invasion, a better drainage route, convenient repeated debridement, and avoidance of the spread of retroperitoneal infection to the abdominal cavity. In addition, retroperitoneal drainage leads to fewer drainage tube problems, including miscounting, displacement, or siphon. The debridement and drainage of pancreatic abscess tissue via the retroperitoneal laparoscopic approach plays an increasingly irreplaceable role in improving patient prognosis and saving healthcare resources and costs. The main procedures described here include laying the patient on the right side, raising the lumbar bridge and then arranging the trocar; establishing the pneumoperitoneum and cleaning the pararenal fat tissues; opening the lateral pyramidal fascia and the perirenal fascia outside the peritoneal reflections; opening the anterior renal fascia and entering the anterior pararenal space from the rear; clearing the necrotic tissue and accumulating fluid; and placing drainage tubes and performing postoperative continuous retroperitoneal lavage.