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Abstract Background Mediterranean diet rich in polyphenolic compounds holds great promise to prevent and alleviate multiple sclerosis (MS), a central nervous system autoimmune disease associated with gut microbiome dysbiosis. Health-promoting effects of natural polyphenols with low bioavailability could be attributed to gut microbiota reconstruction. However, its underlying mechanism of action remains elusive, resulting in rare therapies have proposed for polyphenol-targeted modulation of gut microbiota for the treatment of MS. Results We found that oral ellagic acid (EA), a natural polyphenol rich in the Mediterranean diet, effectively halted the progression of experimental autoimmune encephalomyelitis (EAE), the animal model of MS, via regulating a microbiota-metabolites-immunity axis. EA remodeled the gut microbiome composition and particularly increased the relative abundances of short-chain fatty acids -producing bacteria like Alloprevotella. Propionate (C3) was most significantly up-regulated by EA, and integrative modeling revealed a strong negative correlation between Alloprevotella or C3 and the pathological symptoms of EAE. Gut microbiota depletion negated the alleviating effects of EA on EAE, whereas oral administration of Alloprevotella rava mimicked the beneficial effects of EA on EAE. Moreover, EA directly promoted Alloprevotella rava (DSM 22548) growth and C3 production in vitro. The cell-free supernatants of Alloprevotella rava co-culture with EA suppressed Th17 differentiation by modulating acetylation in cell models. C3 can alleviate EAE development, and the mechanism may be through inhibiting HDAC activity and up-regulating acetylation thereby reducing inflammatory cytokines secreted by pathogenic Th17 cells. Conclusions Our study identifies EA as a novel and potentially effective prebiotic for improving MS and other autoimmune diseases via the microbiota-metabolites-immunity axis. Video Abstract

Abstract Background Skin mottling is a common manifestation of peripheral tissue hypoperfusion, and its severity can be described using the skin mottling score (SMS). This study aims to evaluate the value of the SMS in detecting peripheral tissue hypoperfusion in critically ill patients following cardiac surgery. Methods Critically ill patients following cardiac surgery with risk factors for tissue hypoperfusion were enrolled (n = 373). Among these overall patients, we further defined a hypotension population (n = 178) and a shock population (n = 51). Hemodynamic and perfusion parameters were recorded. The primary outcome was peripheral hypoperfusion, defined as significant prolonged capillary refill time (CRT, > 3.0 s). The characteristics and hospital mortality of patients with and without skin mottling were compared. The area under receiver operating characteristic curves (AUROC) were used to assess the accuracy of SMS in detecting peripheral hypoperfusion. Besides, the relationships between SMS and conventional hemodynamic and perfusion parameters were investigated, and the factors most associated with the presence of skin mottling were identified. Results Of the 373-case overall population, 13 (3.5%) patients exhibited skin mottling, with SMS ranging from 1 to 5 (5, 1, 2, 2, and 3 cases, respectively). Patients with mottling had lower mean arterial pressure, higher vasopressor dose, less urine output (UO), higher CRT, lactate levels and hospital mortality (84.6% vs. 12.2%, p

Background Previous meta-analyses have investigated the efficacy of lipid-lowering therapies for atherosclerotic cardiovascular disease; however, few have focused on patients with acute coronary syndrome (ACS). This meta-analysis aimed to compare the benefits of intensive lipid-lowering therapy with those of background statin therapy in patients with ACS.Methods Searches were performed on PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases for articles published until April 13, 2023. Randomized controlled trials that compared intensive lipid-lowering therapies and background statin therapies in patients with prior ACS and recorded the outcome of three-point major cardiovascular events (MACE) were included. The risk ratio (RR) with 95% confidence interval (CI) was used as a measure of primary and secondary outcomes.Results Nine trials involving 38,640 patients with ACS were identified. Pooled results suggested that intensive lipid-lowering therapies are associated with a reduction in the risk of three-point MACE (RR, 0.88; 95% CI, 0.83–0.94; p

AbstractIt has become almost a stylized fact that sustainable agricultural practices (SAPs) are central to improving productivity, welfare, and food security. However, SAPs adoption rates have been perceived to be generally low in rural China. Understanding the factors influencing SAPs adoption is critical for sustainable food system development. Drawing on a survey of Chinese farmers, this study examined the determinants associated with adoption decision and intensity of multiple SAPs using a Heckman two-stage model. The findings showed that the adoption of SAPs is a multi-stage sophisticated process resulting from the interplay of several elements, such as individual characteristics, government support, and social networks. Age, education, risk attitude, cognition of SAPs, market access, services from Agricultural Science and Technology Park, policy subsidies, technical training, access to credit, and strong ties were the main determinants encouraging SAPs adoption. Adoption decision also significantly depended on farm size; whereas, adoption intensity relied on off-farm activities, town access, and information channels. This study contributes to the literature by identifying the critical determinants of farmers’ adoption behavior of SAPs in China. Furthermore, our findings are of great value to policymakers as they can target the aforementioned factors to achieve higher SAPs adoption.

Pityriasis versicolor, a common skin fungal infection, is typically observed on trunk and limb skin. Here, we highlight an unusual presentation: scalp involvement, often overlooked due to its asymptomatic, mildly scaly patches. We report four pediatric cases, emphasizing the potential underestimation of this scalp variant. This case series underscores the importance of considering this diagnosis in patients with unexplained scalp hypopigmentation, especially in males with short hair who may readily notice these subtle changes. The report contributes to the understanding of this variant's clinical presentation and emphasizes the need for awareness among clinicians to ensure accurate diagnosis and appropriate management.

ABSTRACT Through a long-term micro-area positioning experiment (2006-2017), the precise fertilization locations of spring maize (Zea mays L.) in Jilin, China, were investigated using an embedded cement bucket pot. The effects of different fertilization placements and additional application of organic manure on maize yield, biomass, grain nutrient uptake, and soil fertility were examined. Six treatments were designed: base fertilizer + topdressing shallow application (BF1TD1); base fertilizer deep + topdressing shallow application (BF2TD1); base fertilizer + topdressing deep application (BF1TD2); base fertilizer deep + topdressing deep application (BF2TD2); base fertilizer + topdressing + organic manure shallow application (BF1TD1 + OS); and base fertilizer + topdressing shallow application + organic manure deep application (BF1TD1 + OD). After 12 years of continuous experimentation, the findings revealed that BF2TD2, BF1TD1 + OS, and BF1TD1 + OD exhibited 10.59 %, 25.17 %, and 29.34 % higher average yields than BF1TD1, respectively. Deep topdressing was more beneficial in increasing maize yield and nutrient accumulation, and additionally, increasing the use of organic fertilizer enhanced plant biomass and nutrient uptake. Over the 12 years considered, the soil organic matter in the 0-20 cm and 20-40 cm layers increased by 45.96 % and 80.61 %, respectively, and the soil pH increased from 0.38 to 0.48. In general, the deep application of organic manure was more beneficial for soil retention as it can increase soil fertility in the 0-40 cm layer. Considering the high yield and nutrient absorption and utilization of maize, technical advancement for soil fertilizer in whole-field tillage layers was crucial.

Abstract Background The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) remains unknown. The gut microbiome and its metabolites play important roles in bile acid metabolism, and previous studies have indicated the association of the gut microbiome with ICP. Methods We recruited a cohort of 5100 participants, and 20 participants were enrolled in the severe ICP group, matched with 20 participants in the mild ICP group and 20 controls. 16S rRNA sequencing and nontargeting metabolomics were adapted to explore the gut microbiome and fecal metabolites. Results An increase in richness and a dramatic deviation in composition were found in the gut microbiome in ICP. Decreased Firmicutes and Bacteroidetes abundances and increased Proteobacteria abundances were found in women with severe but not mild ICP compared to healthy pregnant women. Escherichia-Shigella and Lachnoclostridium abundances increased, whereas Ruminococcaceae abundance decreased in ICP group, especially in severe ICP group. The fecal metabolite composition and diversity presented typical variation in severe ICP. A significant increase in bile acid, formate and succinate levels and a decrease in butyrate and hypoxanthine levels were found in women with severe ICP. The MIMOSA model indicated that genera Ruminococcus gnavus group, Lachnospiraceae FCS020 group, and Lachnospiraceae NK4A136 group contributed significantly to the metabolism of hypoxanthine, which was significantly depleted in subjects with severe ICP. Genus Acinetobacter contributed significantly to formate metabolism, which was significantly enriched in subjects with severe ICP. Conclusions Women with severe but not mild ICP harbored a unique gut microbiome and fecal metabolites compared to healthy controls. Based on these profiles, we hypothesized that the gut microbiome was involved in bile acid metabolism through metabolites, affecting ICP pathogenesis and development, especially severe ICP.

Background: Hypertension is a clinical syndrome characterized by elevated systemic arterial blood pressure associated with injury to the heart, kidney, brain, and other organs. Angiotensin receptor neprilysin inhibitors (ARNi), including angiotensin receptor blockers (ARBs) and neprilysin inhibitors (NEPi), have been shown to be safe and effective at reducing blood pressure and alleviating development of target organ injury. This study was used to develop S086 as a novel ARNi and conducted preclinical studies in animal models to evaluate the protective effects of S086 on target organs. Methods: This study used a 14-month-old spontaneously hypertensive rat (SHR) model to evaluate the protective effects of S086 on the cardiovascular system and organs such as heart and kidney by blood pressure monitoring, urine and blood examination, pathological examination, and immunological index detection. Results: After administering S086 orally to the SHR, their blood pressure and levels of renal injury indicators such as serum creatinine and urinary microalbumin were reduced, and myocardial cell necrosis and cardiac fibrosis of the heart were significantly improved. In addition, there were also significantly improvements in the histological lesions of blood vessels and the kidneys. Conclusions: The findings showed that S086 effectively reduced the blood pressure of SHR and had effects on alleviating development of heart, blood vessels and kidney.

Abstract Background Patients receiving surgical treatment of acute type A Aortic Dissection (aTAAD) are common to suffer organ dysfunction in the intensive care unit due to overwhelming inflammation. Previous studies have revealed that glucocorticoids may reduce complications in certain patient groups, but evidence between postoperative glucocorticoids administration and improvement in organ dysfunction after aTAAD surgery are lacking. Methods This study will be an investigator-initiated, prospective, single-blind, randomized, single-center study. Subjects with confirmed diagnosis of aTAAD undergoing surgical treatment will be enrolled and 1:1 randomly assigned to receive either glucocorticoids or normal treatment. All patients in the glucocorticoids group will be given methylprednisolone intravenously for 3 days after enrollment. The primary endpoint will be the amplitude of variation of Sequential Organ Failure Assessment score on post-operative day 4 compared to baseline. Discussion The trial will explore the rationale for postoperative application of glucocorticoids in patients after aTAAD surgery. Trial registration This study has been registered on ClinicalTrials.gov (NCT04734418).

Abstract Background Sepsis is an abnormal immune response after infection, wherein the lung is the most susceptible organ to fail, leading to acute lung injury. To overcome the limitations of current therapeutic strategies and develop more specific treatment, the inflammatory process, in which T cell-derived extracellular vesicles (EVs) play a central role, should be explored deeply. Methods Liquid chromatography–tandem mass spectrometry was performed for serum EV protein profiling. The serum diacylglycerol kinase kappa (DGKK) and endotoxin contents of patients with sepsis-induced lung injury were measured. Apoptosis, oxidative stress, and inflammation in A549 cells, bronchoalveolar lavage fluid, and lung tissues of mice were measured by flow cytometry, biochemical analysis, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, and western blot. Results DGKK, the key regulator of the diacylglycerol (DAG)/protein kinase C (PKC) pathway, exhibited elevated expression in serum EVs of patients with sepsis-induced lung injury and showed strong correlation with sepsis severity and disease progression. DGKK was expressed in CD4+ T cells under regulation of the NF-κB pathway and delivered by EVs to target cells, including alveolar epithelial cells. EVs produced by CD4+ T lymphocytes exerted toxic effects on A549 cells to induce apoptotic cell death, oxidative cell damage, and inflammation. In mice with sepsis induced by cecal ligation and puncture, EVs derived from CD4+ T cells also promoted tissue damage, oxidative stress, and inflammation in the lungs. These toxic effects of T cell-derived EVs were attenuated by the inhibition of PKC and NOX4, the downstream effectors of DGKK and DAG. Conclusions This approach established the mechanism that T-cell-derived EVs carrying DGKK triggered alveolar epithelial cell apoptosis, oxidative stress, inflammation, and tissue damage in sepsis-induced lung injury through the DAG/PKC/NOX4 pathway. Thus, T-cell-derived EVs and the elevated distribution of DGKK should be further investigated to develop therapeutic strategies for sepsis-induced lung injury.

In response to environmental issues, upcycling has become a growing trend in the food industry. Aquasoya is a promising method to upcycle by-product from soybean processing due to its high protein contents and excellent emulsifying ability. In the present research, Aquasoya powder was used an emulsifier to incorporate the antioxidant compounds from perilla skin extract (PSE), namely rosmarinic acid, into oil-in-water (O/W) emulsion system and its physochemical stability was assessed. As a result, droplet size of the emulsion was smaller in PSE-incorporated emulsion (PO, 350.57 ± 9.60 b nm) than the emulsion without PSE (PX, 1045.37 ± 142.63 a nm). Centrifugal photosedimentometry analysis also revealed that the physical stability was significantly improved in PO, and the stability was maintained over 30 d of storage. Furthermore, as PO had a higher ABTS radical scavenging ability and showed slower initial lipid oxidation, it was concluded that PO has a higher antioxidant ability than PX. Conclusively, Aquasoya can be considered as an emulsifier in O/W emulsion with PSE because it can effectively integrate and stabilize the antioxidant substance derived from perilla skin.

Sugarcane is the most important sugar crop and one of the leading energy-producing crops in the world. Ratoon stunting disease (RSD), caused by the bacterium Leifsonia xyli subsp. xyli, poses a huge threat to ratoon crops, causing a significant yield loss in sugarcane. Breeding resistant varieties is considered the most effective and fundamental approach to control RSD in sugarcane. The exploration of resistance genes forms the foundation for breeding resistant varieties through molecular technology. The pglA gene is a pathogenicity gene in L. xyli subsp. xyli, encoding an endopolygalacturonase. In this study, the pglA gene from L. xyli subsp. xyli and related microorganisms was analyzed. Then, a non-toxic, non-autoactivating pglA bait was successfully expressed in yeast cells. Simultaneously the yeast two-hybrid library was generated using RNA from the L. xyli subsp. xyli-infected sugarcane. Screening the library with the pglA bait uncovered proteins that interacted with pglA, primarily associated with ABA pathways and the plant immune system, suggesting that sugarcane employs these pathways to respond to L. xyli subsp. xyli, triggering pathogenicity or resistance. The expression of genes encoding these proteins was also investigated in L. xyli subsp. xyli-infected sugarcane, suggesting multiple layers of regulatory mechanisms in the interaction between sugarcane and L. xyli subsp. xyli. This work promotes the understanding of plant–pathogen interaction and provides target proteins/genes for molecular breeding to improve sugarcane resistance to L. xyli subsp. xyli.

The interfacial transition zone (ITZ) percolation is an effective parameter reflecting the connectivity of ITZs in cementitious materials, and its emergence may accelerate the penetration of inimical ions. In the existing literature on ITZ percolation, aggregates are generally simplified as the identical-shaped particles and the thickness of the ITZ phase around them is set to be uniform, which differs greatly from the realities and may cause the large deviation. To determine the ITZ percolation with the response of different phases in a more realistic way, a more satisfying three-dimensional (3D) polyphase model of concrete is developed, in which the convex ovoids and polyhedrons are separately adopted to represent the sands and gravels. The realistic nonuniform ITZ is also assigned for these aggregates based on their specific sizes and the W/C for the cement matrix. By coupling these models with the continuum percolation theory in statistical physics, the influence of individual phases on the global percolation threshold ϕ agg,c of ITZs is further studied by the simulation. The results reveal that the models here provide a smaller percolation threshold ϕ agg,c than the previous prediction models containing the simplistic uniform ITZs. There is reason to believe that these results in the work would be closer to the actual threshold in the realistic circumstance.

Abstract Background Noninvasive ventilation (NIV) has been widely used in critically ill patients after extubation. However, NIV failure is associated with poor outcomes. This study aimed to determine early predictors of NIV failure and to construct an accurate machine-learning model to identify patients at risks of NIV failure after extubation in intensive care units (ICUs). Methods Patients who underwent NIV after extubation in the eICU Collaborative Research Database (eICU-CRD) were included. NIV failure was defined as need for invasive ventilatory support (reintubation or tracheotomy) or death after NIV initiation. A total of 93 clinical and laboratory variables were assessed, and the recursive feature elimination algorithm was used to select key features. Hyperparameter optimization was conducted with an automated machine-learning toolkit called Neural Network Intelligence. A machine-learning model called Categorical Boosting (CatBoost) was developed and compared with nine other models. The model was then prospectively validated among patients enrolled in the Cardiac Surgical ICU of Zhongshan Hospital, Fudan University. Results Of 929 patients included in the eICU-CRD cohort, 248 (26.7%) had NIV failure. The time from extubation to NIV, age, Glasgow Coma Scale (GCS) score, heart rate, respiratory rate, mean blood pressure (MBP), saturation of pulse oxygen (SpO2), temperature, glucose, pH, pressure of oxygen in blood (PaO2), urine output, input volume, ventilation duration, and mean airway pressure were selected. After hyperparameter optimization, our model showed the greatest accuracy in predicting NIV failure (AUROC: 0.872 [95% CI 0.82–0.92]) among all predictive methods in an internal validation. In the prospective validation cohort, our model was also superior (AUROC: 0.846 [95% CI 0.80–0.89]). The sensitivity and specificity in the prediction group is 89% and 75%, while in the validation group they are 90% and 70%. MV duration and respiratory rate were the most important features. Additionally, we developed a web-based tool to help clinicians use our model. Conclusions This study developed and prospectively validated the CatBoost model, which can be used to identify patients who are at risk of NIV failure. Thus, those patients might benefit from early triage and more intensive monitoring. Trial registration: NCT03704324. Registered 1 September 2018, https://register.clinicaltrials.gov .

Abstract Aims Recombinant human brain natriuretic peptide (rh‐BNP) is commonly used as a decongestive therapy. This study aimed to investigate the instant effects of rh‐BNP on cardiac output and venous return function in post‐cardiotomy patients with congestive heart failure (CHF). Methods and results Twenty‐four post‐cardiotomy heart failure patients were enrolled and received a standard loading dose of rh‐BNP. Haemodynamic monitoring was performed via a pulmonary artery catheter before and after the administration of rh‐BNP. The cardiac output and venous return functions were estimated by depicting Frank‐Starling and Guyton curves. After rh‐BNP infusion, variables reflecting cardiac congestion and venous return function, such as pulmonary artery wedge pressure, mean systemic filling pressure (Pmsf) and venous return resistance index (VRRI), reduced from 15 ± 3 to 13 ± 3 mmHg, from 32 ± 7 to 28 ± 7 mmHg and from 6.7 ± 2.6 to 5.7 ± 1.8 mmHg min m2/L, respectively. Meanwhile, cardiac index, stroke volume index, and the cardiac output function curve remained unchanged per se. The decline in Pmsf [−13% (−22% to −8%)] and VRRI [−12% (−25% to −5%)] was much greater than that in the systemic vascular resistance index [−7% (−14% to 0%)]. In the subgroup analysis of reduced ejection fraction (