Unveiling the molecular mechanisms of Dendrobium officinale polysaccharides on intestinal immunity: An integrated study of network pharmacology, molecular dynamics and in vivo experiments.

Intestinal immunity plays a pivotal role in overall immunological defenses, constructing mechanisms against pathogens while maintaining balance with commensal microbial communities. Existing therapeutic interventions may lead to drug resistance and potential toxicity when immune capacity is compromised. Dendrobium officinale, a traditional Chinese medicine, contains components identified to bolster immunity. Employing network pharmacology strategies, this study identified constituents of Dendrobium officinale and their action targets in the TCMSP and Swiss Target Prediction databases, and compared them with intestinal immunity-related targets. Protein-protein interaction networks revealed the core targets of Dendrobium officinale polysaccharides, encompassing key pathways such as cell proliferation, inflammatory response, and immune reactions, particularly in association with the Toll-like receptor 4. Molecular docking and molecular dynamics simulation further confirmed the high affinity and stability between Dendrobium officinale polysaccharides and Toll-like receptor 4. In vivo experiments demonstrated that Dendrobium officinale polysaccharides modulates the expression of Toll-like receptor 4 and its downstream key proteins in the colonic mucosa of mice. Consequently, these findings suggest that Dendrobium officinale polysaccharides may serve as a potential modulator for intestinal immune functions, with its mechanism potentially related to the Toll-like receptor 4.

Blood pressure response index and clinical outcomes in patients with septic shock: a multicenter cohort study.

BACKGROUND: Sepsis is a leading cause of mortality in intensive care units and vasoactive drugs are widely used in septic patients. The cardiovascular response of septic shock patients during resuscitation therapies and the relationship of the cardiovascular response and clinical outcome has not been clearly described. METHODS: We included adult patients admitted to the ICU with sepsis from Peking Union Medical College Hospital (internal), Medical Information Mart for Intensive Care IV (MIMIC-IV) and eICU Collaborative Research Database (eICU-CRD). The Blood Pressure Response Index (BPRI) was defined as the ratio between the mean arterial pressure and the vasoactive-inotropic score. BRRI was compared with existing risk scores on predicting in-hospital death. The relationship between BPRI and in-hospital mortality was calculated. A XGBoost's machine learning model identified the features that influence short-term changes in BPRI. FINDINGS: There were 2139, 9455, and 4202 patients in the internal, MIMIC-IV and eICU-CRD cohorts, respectively. BPRI had a better AUROC for predicting in-hospital mortality than SOFA (0.78 vs. 0.73, p = 0.01) and APS (0.78 vs. 0.74, p = 0.03) in the internal cohort. The estimated odds ratio for death per unit decrease in BPRI was 1.32 (95% CI 1.20-1.45) when BPRI was below 7.1 vs. 0.99 (95% CI 0.97-1.01) when BPRI was above 7.1 in the internal cohort; similar relationships were found in MIMIC-IV and eICU-CRD. Respiratory support and latest cumulative 12-h fluid balance were intervention-related features influencing BPRI. INTERPRETATION: BPRI is an easy, rapid, precise indicator of the response of patients with septic shock to vasoactive drugs. It is a comparable and even better predictor of prognosis than SOFA and APS in sepsis and it is simpler and more convenient in use. The application of BPRI could help clinicians identify potentially at-risk patients and provide clues for treatment. FUNDING: Fundings for the Beijing Municipal Natural Science Foundation; the National High Level Hospital Clinical Research Funding; the CAMS Innovation Fund for Medical Sciences (CIFMS) from Chinese Academy of Medical Sciences and the National Key R&D Program of China, Ministry of Science and Technology of the People's Republic of China.

Study on the mechanism of macrophages activated by phosphoesterified rehmanniae polysaccharide on human gastric cancer cells.

Gastric cancer(GC)is one of the most common gastrointestinal malignant tumors in the world, requiring the development of novel therapeutic agents with reduced toxicity. Rehmannia polysaccharide (RPS) possesses immunomodulatory and anti-tumor properties, yet its efficacy is suboptimal. To enhance its biological activity, we subjected RPS to molecular modifications, resulting in phosphorylated Rehmannia polysaccharides (P-RPS). Using the mixed phosphate method, we synthesized P-RPS and optimized the synthesis conditions through a combination of single-factor and response surface methodologies. In vitro studies on P-RPS's anti-tumor activity showed no direct influence on the viability of GC cells. However, P-RPS induced the transformation of PMA-activated THP-1 cells into the M1 phenotype. We collected conditioned medium (CM) of THP-1 cells to stimulate gastric cancer cells and CM-P-RPS significantly promoted apoptosis of gastric cancer cells and inhibited cell proliferation, and reduced cell migration. Mechanistically, CM-P-RPS inhibits the Wnt/ß-catenin signaling pathway through LGR6, leading to the suppression of tumor growth. Furthermore, P-RPS demonstrated a significant inhibitory effect on tumor growth in vivo, suggesting its potential as a promising therapeutic agent for GC treatment.

Construction and validation of the prognostic nomogram model for patients with diffuse-type gastric cancer based on the SEER database.

OBJECTIVE: The prognostic factors of diffuse GC patients were screened the prognostic nomogram was constructed, and the prediction accuracy was verified. METHODS: From 2006 to 2018, there were 2877 individuals pathologically diagnosed with diffuse gastric cancer; the clinicopathological features of these patients were obtained from the SEER database & randomly divided into a training cohort (1439) & validation cohort (1438).To create prognostic nomograms & choose independent prognostic indicators to predict the overall survival (OS) of 1, 3, & 5 years, log-rank & multivariate COX analysis were utilized & discrimination ability of nomogram prediction using consistency index and calibration curve. RESULTS: Age, T, N, M, TNM, surgical status, chemotherapy status, & all seven markers were independent predictors of OS (P < 0.05), & a nomogram of OS at 1, 3, & 5 years was created using these independent predictors. The nomogram's c-index was 0.750 (95% CI 0.734 ~ 0.766), greater than the TNM staging framework 0.658 (95%CI 0.639 ~ 0.677); the c-index was 0.753 (95% CI 0.737 ~ 0.769) as well as superior to the TNM staging mechanism 0.679 (95% CI 0.503-0.697). According to the calibration curve, the projected survival rate using the nomogram & the actual survival rate are in good agreement. CONCLUSIONS: Prognostic nomograms are useful tools for physicians to assess every individual's individualised prognosis & create treatment strategies for those with diffuse gastric cancer. They can reliably predict the prognosis for individuals with diffuse gastrointestinal carcinoma.

Glutamate acts on acid-sensing ion channels to worsen ischaemic brain injury.

Glutamate is traditionally viewed as the first messenger to activate NMDAR (N-methyl-D-aspartate receptor)-dependent cell death pathways in stroke1,2, but unsuccessful clinical trials with NMDAR antagonists implicate the engagement of other mechanisms3-7. Here we show that glutamate and its structural analogues, including NMDAR antagonist L-AP5 (also known as APV), robustly potentiate currents mediated by acid-sensing ion channels (ASICs) associated with acidosis-induced neurotoxicity in stroke4. Glutamate increases the affinity of ASICs for protons and their open probability, aggravating ischaemic neurotoxicity in both in vitro and in vivo models. Site-directed mutagenesis, structure-based modelling and functional assays reveal a bona fide glutamate-binding cavity in the extracellular domain of ASIC1a. Computational drug screening identified a small molecule, LK-2, that binds to this cavity and abolishes glutamate-dependent potentiation of ASIC currents but spares NMDARs. LK-2 reduces the infarct volume and improves sensorimotor recovery in a mouse model of ischaemic stroke, reminiscent of that seen in mice with Asic1a knockout or knockout of other cation channels4-7. We conclude that glutamate functions as a positive allosteric modulator for ASICs to exacerbate neurotoxicity, and preferential targeting of the glutamate-binding site on ASICs over that on NMDARs may be strategized for developing stroke therapeutics lacking the psychotic side effects of NMDAR antagonists.

PAI-1 Deficiency Promotes NET-mediated Pyroptosis and Ferroptosis during Pseudomonas Aeruginosa-induced Acute Lung Injury by Regulating the PI3K/MAPK/AKT Axis.

Circulating neutrophil extracellular trap (NET) formation is an adaptive process during acute lung injury (ALI). The important role of plasminogen activator inhibitor (PAI)-1 in NET formation during ALI remains unclear. This research intends to examine the impacts of the decrease in PAI-1 levels on NET formation and the underlying mechanism. We found a relative association between the increase in plasma NET levels and thromboinflammation-induced lung damage in patients with ARDS. PAI-1 knockout (KO) mice exhibited significant increases in Pseudomonas aeruginosa (PAO1 strain)-induced ALI, inflammation, inflammatory cell accumulation, and proinflammatory cytokine secretion, and wild-type mice exhibited the opposite changes. During PAO1-induced ALI, PAI-1 KO increased NET release and the levels of prothrombotic markers in mice. PAI-1 deficiency also promoted NET formation and NET-mediated pyroptosis and ferroptosis by activating the PI3K/MAPK/AKT pathway in a PAO1-induced ALI mouse model. In conclusion, PAI-1 KO exacerbated PAO1-induced pneumonia-associated injury and contributed to NET-mediated pyroptosis and ferroptosis through PI3K/MAPK/AKT pathway activation. Thus, targeting PAI-1 and NETs may be a promising therapeutic approach for ameliorating pneumonia and thromboinflammation-associated ALI.

Electrospun collagen/chitosan composite fibrous membranes for accelerating wound healing.

The protein-polysaccharide nanofibers have attracted intensive attention in promoting wound healing, due to their components and nanoscale fibrous structure that mimics the native extracellular matrix (ECM). For the full-thickness wounds, in addition to promoting healing, hemostatic property and antibacterial activity are also of critical importance. However, currently, protein-polysaccharide-based nanofiber membranes exhibit poor mechanical properties, lack inherent hemostatic and antibacterial capabilities, as well as the ability to promote tissue repair. In this study, we developed composited membranes, which were composed of collagen (Col) and chitosan (Chs), through solvent alteration and post-processing, the membranes showed enhanced stability under physiological conditions, proper hydrophilic performance and improved mechanical property. Appropriated porosity and water vapor transmission rate, which benefit to wound healing, were detected among all the membranes except for Col membrane. Aimed at wound dressing, hemocompatibility, antibacterial activity and cell proliferation of the electrospun membranes were evaluated. The results indicated that the Col/Chs composited membranes exhibited superior blood clotting capacity, and the membranes with Chs exceeding 60% possessed sufficient antibacterial activity. Moreover, compared with Chs nanofibers, significant increase in cell grow was detected in Col/Chs (1:3) membrane. Taken together, the electrospun membrane with multiple properties favorable to wound healing, superior blood coagulation, sufficient antibacterial performance and promoting cell proliferation property make it favourable candidate for full-thickness skin wound healing.

Modeling cellular responses to serum and vitamin D in microgravity using a human kidney microphysiological system.

The microgravity environment aboard the International Space Station (ISS) provides a unique stressor that can help understand underlying cellular and molecular drivers of pathological changes observed in astronauts with the ultimate goals of developing strategies to enable long- term spaceflight and better treatment of diseases on Earth. We used this unique environment to evaluate the effects of microgravity on kidney proximal tubule epithelial cell (PTEC) response to serum exposure and vitamin D biotransformation capacity. To test if microgravity alters the pathologic response of the proximal tubule to serum exposure, we treated PTECs cultured in a microphysiological system (PT-MPS) with human serum and measured biomarkers of toxicity and inflammation (KIM-1 and IL-6) and conducted global transcriptomics via RNAseq on cells undergoing flight (microgravity) and respective controls (ground). Given the profound bone loss observed in microgravity and PTECs produce the active form of vitamin D, we treated 3D cultured PTECs with 25(OH)D3 (vitamin D) and monitored vitamin D metabolite formation, conducted global transcriptomics via RNAseq, and evaluated transcript expression of CYP27B1, CYP24A1, or CYP3A5 in PTECs undergoing flight (microgravity) and respective ground controls. We demonstrated that microgravity neither altered PTEC metabolism of vitamin D nor did it induce a unique response of PTECs to human serum, suggesting that these fundamental biochemical pathways in the kidney proximal tubule are not significantly altered by short-term exposure to microgravity. Given the prospect of extended spaceflight, more study is needed to determine if these responses are consistent with extended (>6 months) exposure to microgravity.

Design and characterization of a hybrid PET detector with DOI capability.

BACKGROUND: Monolithic or semi-monolithic detectors are attractive for positron emission tomography (PET) scanners with depth-of-interaction (DOI) capability. However, they often require complicated calibrations to determine the interaction positions of gamma photons. PURPOSE: We introduce a novel hybrid detector design that combines pixelated and semi-monolithic elements to achieve DOI capability while simplifying the calibrations for positioning. METHODS: A prototype detector with eight hybrid lutetium-yttrium oxyorthosilicate (LYSO) layers having dimensions of 25.8 × 12.9 × 15 mm3 was constructed. The energy-weighted and energy-squared weighted averages were used for estimating the x- (pixelated direction) and y-positions (non-pixelated direction). Pseudo-pixels were defined as discrete areas on the flood image based on the crystal look-up table (LUT). The intrinsic spatial resolutions in the pixelated and non-pixelated directions were measured. The ratio of the maximum to the sum of the multipixel photon counter (MPPC) signals was used to estimate the DOI positions. The coincidence timing resolution (CTR) was measured using the average and energy-weighted average of the earliest n time stamps. Two energy windows of 250-700 and 400-600 keV were applied for the measurements. RESULTS: The pattern of the flood images showed discrete event clusters, demonstrating that simple calibrations for determining the x- and y-positions of events could be achieved. Under 400-600 keV energy window, the average intrinsic spatial resolutions were 1.15 and 1.34 mm for the pixelated and non-pixelated directions; the average DOI resolution of the second row of pseudo-pixels was 5.1 mm in full width at half maximum (FWHM); when using the energy-weighted average of the earliest four-time stamps, the best CTR of 350 ps was achieved. Applying a broader energy window of 250-700 keV only slightly degrades the DOI resolution while maintaining the intrinsic resolution; the best CTR degrades to 410 ps. CONCLUSIONS: The proposed hybrid detector concept was verified, and a prototype detector showed high performance for 3D positioning and timing resolution. The novel detector concept shows promise for preclinical and clinical PET scanners with DOI capability.

New Perspective to Evaluate the Carbon Offsetting by Urban Blue-Green Infrastructure: Direct Carbon Sequestration and Indirect Carbon Reduction.

Urban blue-green infrastructure (BGI) offers a multitude of ecological advantages to residents, thereby playing a pivotal role in fortifying urban resilience and fostering the development of climate-resilient cities. Nonetheless, current research falls short of a comprehensive analysis of BGI's overall potential for carbon reduction and its indirect carbon reduction impact. To fill this research gap, we utilized the integrated valuation of ecosystem services and trade-offs model and remote sensing estimation algorithm to quantify the direct carbon sequestration and resultant indirect carbon reduction facilitated by the BGI within the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) (China). To identify the regions that made noteworthy contributions to carbon offsets and outliers, spatial autocorrelation analysis was also employed. The findings of this study reveal that in 2019, the BGI within the study area contributed an overall carbon offset of 1.5 × 108 t·C/yr, of which 3.5 × 107 and 11.0 × 107 t·C/yr were the result of direct carbon sequestration and indirect carbon reduction, respectively. The GBA's total CO2 emissions were 1.1 × 108 t in 2019. While the direct carbon sequestration offset 32.0% of carbon emissions, the indirect carbon reduction mitigated 49.9% of potential carbon emissions. These results highlight the critical importance of evaluating BGI's indirect contribution to carbon reduction. The findings of this study provide a valuable reference for shaping management policies that prioritize the protection and restoration of specific areas, thereby facilitating the harmonized development of carbon offset capabilities within urban agglomerations.

The utilization of chitosan/Bletilla striata hydrogels to elevate anti-adhesion, anti-inflammatory and pro-angiogenesis properties of polypropylene mesh in abdominal wall repair.

Polypropylene (PP) mesh is commonly used in abdominal wall repair due to its ability to reduce the risk of organ damage, infections and other complications. However, the PP mesh often leads to adhesion formation and does not promote functional tissue repair. In this study, we synthesized one kind of aldehyde Bletilla striata polysaccharide (BSPA) modified chitosan (CS) hydrogel based on Schiff base reaction. The hydrogel exhibited a porous network structure, a highly hydrophilic surface and good biocompatibility. We wrapped the PP mesh inside the hydrogel and evaluated the performance of the resulting composites in a bilateral 1 × 1.5 cm abdominal wall defect model in rats. The results of gross observation, histological staining and immunohistochemical staining demonstrated the positive impact of the CS hydrogel on anti-adhesion and wound healing effects. Notably, the addition of BSPA to the CS hydrogel further improved the performance of the composites in vivo, promoting wound healing by enhancing collagen deposition and capillary rearrangement. This study suggested that the BSPA-modified CS hydrogel significantly promoted the anti-adhesion, anti-inflammatory and pro-angiogenesis properties of PP meshes during the healing process. Overall, this work offers a novel approach to the design of abdominal wall repair patches.

Optimize individualized energy delivery for septic patients using predictive deep learning models.

BACKGROUND AND OBJECTIVES: We aim to establish deep learning models to optimize the individualized energy delivery for septic patients. METHODS AND STUDY DESIGN: We conducted a study of adult septic patients in ICU, collecting 47 indicators for 14 days. We filtered out nutrition-related features and divided the data into datasets according to the three metabolic phases proposed by ESPEN: acute early, acute late, and rehabilitation. We then established optimal energy target models for each phase using deep learning and conducted external validation. RESULTS: A total of 179 patients in training dataset and 98 patients in external validation dataset were included in this study, and total data size was 3115 elements. The age, weight and BMI of the patients were 63.05 (95%CI 60.42-65.68), 61.31(95%CI 59.62-63.00) and 22.70 (95%CI 22.21-23.19), respectively. And 26.0% (72) of the patients were female. The models indicated that the optimal energy targets in the three phases were 900kcal/d, 2300kcal/d, and 2000kcal/d, respectively. Excessive energy intake increased mortality rapidly in the early period of the acute phase. Insufficient energy in the late period of the acute phase significantly raised the mortality as well. For the rehabilitation phase, too much or too little energy delivery were both associated with elevated death risk. CONCLUSIONS: Our study established time-series prediction models for septic patients to optimize energy delivery in the ICU. We recommended permissive underfeeding only in the early acute phase. Later, increased energy intake may improve survival and settle energy debts caused by underfeeding.

Trunk distortion weakens the tree productivity revealed by half-sib progeny determination of Pinus yunnanensis.

Twisted trunks are not uncommon in trees, but their effects on tree growth are still unclear. Among coniferous tree species, the phenomenon of trunk distortion is more prominent in Pinus yunnanensis. To expand the germplasm of genetic resources, we selected families with excellent phenotypic traits to provide material for advanced generation breeding. The progeny test containing 93 superior families (3240 trees) was used as the research material. Phenotypic measurements and estimated genetic parameters (family heritability, realistic gain and genetic gain) were performed at 9, 15, and 18 years of age, respectively. The genetic evaluation yielded the following results (1) The intra-family variance component of plant height (PH) was greater than that of the inter-family, while the inter-family variance components of other traits (diameter at breast height (DBH), crown diameter (CD), height under branches (HUB), degree of stem-straightness (DS)) were greater than that of the intra-family, indicating that there was abundant variation among families and potential for selection. (2) At half rotation period (18 years old), there was a significant correlation among the traits. The proportion of trees with twisted trunks (level 1-3 straightness) reached 48%. The DS significantly affected growth traits, among which PH and DBH were the most affected. The volume loss rate caused by twisted trunk was 18.06-56.75%, implying that trunk distortion could not be completely eliminated after an artificial selection. (3) The influence of tree shape, crown width, and trunk on volume increased, and the early-late correlation between PH, DBH and volume was extremely significant. The range of phenotypic coefficient of variation, genetic variation coefficient and family heritability of growth traits (PH, DBH, and volume) were 44.29-127.13%, 22.88-60.87%, and 0.79-0.83, respectively. (4) A total of 21 superior families were selected by the method of membership function combined with independent selection. Compared with the mid-term selection (18 years old), the accuracy of early selection (9 years old) reached 77.5%. The selected families' genetic gain and realistic gain range were 5.79-19.82% and 7.12-24.27%, respectively. This study can provide some useful reference for the breeding of coniferous species.

The coagulation status in women of endometriosis with stage IV.

BACKGROUND: Endometriosis is considered as a systemic disease with the presence of proinflammatory cytokines in the circulation, which drives hypercoagulable state of endometriosis. Currently, endometriosis is classified into four stages: I (minimal), II (mild), III (moderate) and IV (severe). The aim of this study is to investigate the correlations between inflammatory markers and coagulation factors in patients diagnosed of endometriosis with stage IV. METHODS: This retrospective case-control study included 171 endometriosis patients with stage IV and 184 controls. Continuous data were expressed by mean ± standard deviation. Mann-Whitney U and χ2 tests were used to compare the medians and frequencies among the groups. Spearman analysis was conducted to determine the correlation among the measured parameters. The diagnostic values of the parameters differentiating endometriomas were tested by receiver operating characteristic (ROC) curve. RESULTS: The time of activated partial thromboplastin time (APTT) was decreased and the concentration of fibrinogen (FIB) and neutrophil-to-lymphocyte ratio (NLR) were increased in women of endometriosis with stage IV. The APTT were negatively correlated with NLR while the concentrations of FIB were positively correlated with NLR. The ROC analysis showed that the Area under the curve (AUC) of FIB was 0.766 (95% confidence interval:0.717-0.814) with sensitivity and specificity reaching 86.5 and 60.9%, respectively. The AUC of CA125 and CA199 was 0.638 (95% confidence interval: 0.578-0.697), 0.71 (95% confidence interval: 0.656-0.763) with sensitivity and specificity reaching 40.9 and 91.8%, 80.7 and 56.5% respectively. The combination of these factors showed the highest AUC of 0.895 (0.862-0.927) with sensitivity of 88.9% and specificity of 77.7%. CONCLUSION: In the present study, we found that inflammatory factors showed significant correlation with APTT or FIB in endometriosis with stage IV. Moreover, the coagulation factors combined with CA125 and CA199 were more reliable for identifying the endometriosis with stage IV.

MGST3 regulates BACE1 protein translation and amyloidogenesis by controlling the RGS4-mediated AKT signaling pathway.

Microsomal glutathione transferase 3 (MGST3) regulates eicosanoid and glutathione metabolism. These processes are associated with oxidative stress and apoptosis, suggesting that MGST3 might play a role in the pathophysiology of Alzheimer's disease (AD). Here, we report that knockdown (KD) of MGST3 in cell lines reduced the protein level of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and the resulting amyloidogenesis. Interestingly, MGST3 KD did not alter intracellular ROS level but selectively reduced the expression of apoptosis indicators which could be associated with the receptor of cysteinyl leukotrienes (cysLTs), the downstream metabolites of MGST3 in arachidonic acid pathway. We then showed that the effect of MGST3 on BACE1 was independent of cysLTs but involved a translational mechanism. Further RNA-seq analysis identified that regulator of G-protein signaling 4 (RGS4) was a target gene of MGST3. Silencing of RGS4 inhibited BACE1 translation and prevented MGST3 KD-mediated reduction of BACE1. The potential mechanism was related to AKT activity, as the protein level of phosphorylated AKT (p-AKT) was significantly reduced by silencing of MGST3 and RGS4, and the AKT inhibitor abolished the effect of MGST3/RGS4 on p-AKT and BACE1. Together, MGST3 regulated amyloidogenesis by controlling BACE1 protein expression, which was mediated by RGS4 and downstream AKT signaling pathway.

Development and validation of machine learning models to predict MDRO colonization or infection on ICU admission by using electronic health record data.

BACKGROUND: Multidrug-resistant organisms (MDRO) pose a significant threat to public health. Intensive Care Units (ICU), characterized by the extensive use of antimicrobial agents and a high prevalence of bacterial resistance, are hotspots for MDRO proliferation. Timely identification of patients at high risk for MDRO can aid in curbing transmission, enhancing patient outcomes, and maintaining the cleanliness of the ICU environment. This study focused on developing a machine learning (ML) model to identify patients at risk of MDRO during the initial phase of their ICU stay. METHODS: Utilizing patient data from the First Medical Center of the People's Liberation Army General Hospital (PLAGH-ICU) and the Medical Information Mart for Intensive Care (MIMIC-IV), the study analyzed variables within 24 h of ICU admission. Machine learning algorithms were applied to these datasets, emphasizing the early detection of MDRO colonization or infection. Model efficacy was evaluated by the area under the receiver operating characteristics curve (AUROC), alongside internal and external validation sets. RESULTS: The study evaluated 3,536 patients in PLAGH-ICU and 34,923 in MIMIC-IV, revealing MDRO prevalence of 11.96% and 8.81%, respectively. Significant differences in ICU and hospital stays, along with mortality rates, were observed between MDRO positive and negative patients. In the temporal validation, the PLAGH-ICU model achieved an AUROC of 0.786 [0.748, 0.825], while the MIMIC-IV model reached 0.744 [0.723, 0.766]. External validation demonstrated reduced model performance across different datasets. Key predictors included biochemical markers and the duration of pre-ICU hospital stay. CONCLUSIONS: The ML models developed in this study demonstrated their capability in early identification of MDRO risks in ICU patients. Continuous refinement and validation in varied clinical contexts remain essential for future applications.

Tissue microenvironment induces tissue specificity of ILC2.

Type 2 innate lymphoid cells were found to be members of the innate immune cell family, which is involved in innate and adaptive immunity to resist the invasion of foreign antigens and induce allergic reactions caused by allergens. The advancement of ILC2 research has pointed out that ILC2s have a high degree of diversity, challenging the notion of their homogeneity as a cellular population. An increasing number of studies indicate that ILC2 is a cell population with tissue specificity which can be induced by the tissue microenvironment. In addition, crosstalk between tissues can change ILC2 functions of migration and activation. Here, we emphasize that ILC2 undergoes adaptive changes under the regulation of the tissue microenvironment and distant tissues, thereby coordinating the organization's operation. In addition, ILC2 alterations induced by the tissue microenvironment are not limited to the ILC2 cell population, and ILC2 can also transdifferentiate into another class of ILC cell population (ILC1 or ILC3). In this review, we summarized the tissue-specific effects of ILC2 by tissue microenvironment and focused on the function of ILC2 in inter-tissue crosstalk. Lastly, we discussed the transdifferentiations of ILC2 caused by the abnormal change in tissue environment.

Design of a miniaturized dual circularly polarized implantable antenna by using characteristic mode method.

The characteristic mode method is used to design a miniaturized dual-band dual circularly polarized (CP) implantable antenna operating in ISM bands. The miniaturization and dual-band characteristics are gained by using the slotting method and by inserting a short-circuit probe between the radiation patch and the ground plane. We use the characteristic mode method to study the current distribution of circular radiation patches with T-shaped slots in different modes. After opening a cross-shaped slot at the center of the radiation patch and the ground plane, we obtained two orthogonal modes with equal amplitude and phase difference of 90° in two operating frequency bands, ultimately achieving CP characteristics of the antenna. Its overall size is only π ×(0.014 λ 0)2 × 0.0027 λ 0, smaller than other CP implantable antennas with similar performances, and it has satisfactory radiation efficiency and gain characteristics. Measurements show that it can operate in the ISM bands of 0.9 and 2.4 GHz with an effective 3 dB axial ratio bandwidth greater than 220 MHz (0.87 to 1.09 GHz, 22.45%) and 230 MHz (2.31 to 2.54 GHz, 9.48%), and its peak gain is - 29.5 dBi and - 19.2 dBi, respectively. And, this design complies with IEEE safety guidelines.

Association between vitamin A intake and depression among patients with heart failure.

AIMS: We aim to investigate the association between vitamin A intake and depression among patients with heart failure (HF). METHODS AND RESULTS: In this cross-sectional study, data of HF patients were extracted from the National Health and Nutrition Examination Survey (NHANES) 2007-2020. The independent variable was vitamin A intake, and the dependent variable was depression. Weighted univariate and multivariate logistic regression models were performed to explore the association of vitamin A intake with depression in HF patients. A total of 999 HF patients were included, with a mean age of 66.19 (0.51) years, and 566 (52.49%) were male. And 197 patients have depression. Vitamin A intake ≥731.38 mcg was associated with lower incidence of depression [odds ratio (OR) = 0.37; 95% confidence interval (CI): 0.18-0.76] in HF patients. Similarly, the relationship between high vitamin A intake and lower odds of depression were also observed in subgroups of those aged >65 years (OR = 0.16; 95% CI: 0.04-0.55), males (OR = 0.35; 95% CI: 0.14-0.86), without hypertension (OR = 0.25; 95% CI: 0.11-0.58), without diabetes (OR = 0.30; 95% CI: 0.11-0.78), with hyperlipidaemia (OR = 0.23; 95% CI: 0.09-0.64), and with chronic kidney disease (CKD) (OR = 0.32; 95% CI: 0.13-0.80). CONCLUSIONS: High vitamin A intake was associated with lower odds of depression in HF patients. Appropriate vitamin A supplementation may have potential benefit to the prevention of depression in HF patients. Additional prospective large-scale studies are required to confirm whether or not vitamin A could lead to decrease in depression symptoms.