Preventive and reparative potentials of heat-inactivated and viable commensal Bacillus pumilus SE5 in ameliorating the adverse impacts of high soybean meal in grouper (Epinephelus coioides).

Probiotic Bacillus pumilus SE5, heat-inactivated (HSE5) or active (ASE5), were supplemented to high soybean meal (HSM) (36 %) diet at whole term (0-56 days) and middle term (29-56 days) to investigate the preventing and repairing effects of B. pumilus SE5 in ameliorating the adverse effects of HSM in Epinephelus coioides. The results suggested that the HSM significantly decreased the weight gain rate (WGR), specific growth rate (SGR), and increased the feed conversion rate (FCR) at day 56 (P < 0.05), while HSE5 and ASE5 promoted the growth performance. The HSE5 and ASE5 showed preventive and reparative functions on the antioxidant capacity and serum immunity, with significantly increased the total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-PX) activities, and reduced malondialdehyde (MDA) level, and increased acid phosphatase (ACP), alkaline phosphatase (AKP), immunoglobulin M (IgM) and complement 3 (C3). The HSM impaired the intestinal health (destroyed the intestinal structure, significantly increased the contents of serum D-lactic acid and diamine oxidase, and reduced the expressions of claudin-3 and occludin), while HSE5 and ASE5 improved them at whole term and middle term. The HSM impaired the intestinal microbiota and reduced its diversity, and the HSE5 or ASE5 improved the intestinal microbiota (especially at whole term). HSE5 and ASE5 improved the intestinal mRNA expressions of anti-inflammatory genes (il-10 and tgf-ß1) and reduced the expressions of pro-inflammatory genes (il-1ß, il-8, il-12), and promoted the expressions of humoral immune factor-related genes (cd4, igm, mhcII-α) and antimicrobial peptide genes (ß-defensin, epinecidin-1 and hepcidin-1), and decreased the expressions of NF-κB/MAPK signaling pathway-related genes (ikk-α, nf-κb, erk-1), and improved the expressions of MAPK signaling pathway-related gene p38-α (P < 0.05). In conclusion, the heat-inactivated and active B. pumilus SE5 effectively prevented and repaired the suppressive effects of soybean meal in E. coioides, which underscored the potential of B. pumilus SE5 as a nutritional intervention agent in HSM diet in aquaculture.

Lanthanium nitride LaN9 featuring azide units: the first metal nine-nitride as a high-energy-density material.

High-pressure phase diagrams of the La-N binary system were systematically constructed using the CALYPSO method and first-principles calculations. In addition to the pressure-induced La-N compounds reported previously, we have uncovered a hitherto unknown LaN9 structure in Pm3̄ symmetry stabilized within a narrow pressure range of 20-24.5 GPa. Notably, LaN9 stands as the first thermodynamically stable metal nine-nitrogen compound, featuring centrosymmetric linear N3 anion units and an edge-sharing LaN12 icosahedron. Charge transfer between the La and N atoms plays a crucial role in facilitating structural stability. Furthermore, we identified a novel Cm phase for LaN8, which has a lower enthalpy compared to the previously reported phase. N atoms in Cm LaN8 are polymerized into infinite N∞ chains. Calculations demonstrate the potential recoverability of LaN9 and Cm LaN8 under atmospheric conditions while preserving their initial polynitrogen configuration. From the perspective of detonation pressure and detonation velocity, LaN9 and Cm LaN8 exhibit excellent explosive performance in comparison to TNT and HMX, with estimated energy densities of 0.9 and 1.54 kJ g-1, respectively, indicating their potential utility as high-energy-density materials.

Analyzing the correlation between quinolone-resistant Escherichia coli resistance rates and climate factors: A comprehensive analysis across 31 Chinese provinces.

BACKGROUND: The increasing problem of bacterial resistance, particularly with quinolone-resistant Escherichia coli (QnR eco) poses a serious global health issue. METHODS: We collected data on QnR eco resistance rates and detection frequencies from 2014 to 2021 via the China Antimicrobial Resistance Surveillance System, complemented by meteorological and socioeconomic data from the China Statistical Yearbook and the China Meteorological Data Service Centre (CMDC). Comprehensive nonparametric testing and multivariate regression models were used in the analysis. RESULT: Our analysis revealed significant regional differences in QnR eco resistance and detection rates across China. Along the Hu Huanyong Line, resistance rates varied markedly: 49.35 in the northwest, 54.40 on the line, and 52.30 in the southeast (P = 0.001). Detection rates also showed significant geographical variation, with notable differences between regions (P < 0.001). Climate types influenced these rates, with significant variability observed across different climates (P < 0.001). Our predictive model for resistance rates, integrating climate and healthcare factors, explained 64.1% of the variance (adjusted R-squared = 0.641). For detection rates, the model accounted for 19.2% of the variance, highlighting the impact of environmental and healthcare influences. CONCLUSION: The study found higher resistance rates in warmer, monsoon climates and areas with more public health facilities, but lower rates in cooler, mountainous, or continental climates with more rainfall. This highlights the strong impact of climate on antibiotic resistance. Meanwhile, the predictive model effectively forecasts these resistance rates using China's diverse climate data. This is crucial for public health strategies and helps policymakers and healthcare practitioners tailor their approaches to antibiotic resistance based on local environmental conditions. These insights emphasize the importance of considering regional climates in managing antibiotic resistance.

High dietary wheat starch negatively regulated growth performance, glucose and lipid metabolisms, liver and intestinal health of juvenile largemouth bass, Micropterus salmoides.

Largemouth bass (Micropterus salmoides) were fed with three diets containing 6%, 12%, and 18% wheat starch for 70 days to examine their impacts on growth performance, glucose and lipid metabolisms, and liver and intestinal health. The results suggested that the 18% starch group inhibited the growth, and improved the hepatic glycogen content compared with the 6% and 12% starch groups (P < 0.05). High starch significantly improved the activities of glycolysis-related enzymes, hexokinase (HK), glucokinase (GK), phosphofructokinase (PFK), and pyruvate kinase (PK) (P < 0.05); promoted the mRNA expression of glycolysis-related phosphofructokinase (pfk); decreased the activities of gluconeogenesis-related enzymes, pyruvate carboxylase (PC), and phosphoenolpyruvate carboxykinase (PEPCK); and reduced the mRNA expression of gluconeogenesis-related fructose-1,6-bisphosphatase-1(fbp1) (P < 0.05). High starch reduced the hepatic mRNA expressions of bile acid metabolism-related cholesterol hydroxylase (cyp7a1) and small heterodimer partner (shp) (P < 0.05), increased the activity of hepatic fatty acid synthase (FAS) (P < 0.05), and reduced the hepatic mRNA expressions of lipid metabolism-related peroxisome proliferator-activated receptor α (ppar-α) and carnitine palmitoyltransferase 1α (cpt-1α) (P < 0.05). High starch promoted inflammation; significantly reduced the mRNA expressions of anti-inflammatory cytokines transforming growth factor-ß1 (tgf-ß1), interleukin-10 (il-10), and interleukin-11ß (il-11ß); and increased the mRNA expressions of pro-inflammatory cytokine tumor necrosis factor-α (tnf-α), interleukin-1ß (il-1ß), and interleukin-8 (il-8) in the liver and intestinal tract (P < 0.05). Additionally, high starch negatively influenced the intestinal microbiota, with the reduced relative abundance of Trichotes and Actinobacteria and the increased relative abundance of Firmicutes and Proteobacteria. In conclusion, low dietary wheat starch level (6%) was more profitable to the growth and health of M. salmoides, while high dietary starch level (12% and 18%) could regulate the glucose and lipid metabolisms, impair the liver and intestinal health, and thus decrease the growth performance of M. salmoides.

Clinical Features and Risk Factors for Baker's Cyst in Patients with Rheumatoid Arthritis.

OBJECTIVES: Baker's cyst (BC) is a complex complication of rheumatoid arthritis (RA), with a poor prognosis. This paper aimed to analyze the clinical features and risk factors for BC in patients with RA to assist clinicians in early warning and appropriate action. METHODS: The Clinical features of hospitalized RA patients with knee affected were analyzed retrospectively. The R software was used for the statistical analysis, while logistic regression analyses were used to determine independent risk factors. RESULTS: A total of 367 RA patients with knee affected were studied, and BC was diagnosis in 15.3% of them. The BC group exhibited a higher proportion of knee-only affected than the non-BC group (p < 0.05), while the attributes linked to disease activity exhibited no disparity. Logistic regression analyses selected two independent risk factors for BC: knee-only affected and anemia. 26.8% of patients with BC developed rupture, exhibiting a higher proportion of knee-only affected (p < 0.05), compared to those unruptured. CONCLUSIONS: The occurrence and rupture of BC in RA patients were significantly related to local inflammation, but not to systemic one. Incorporating local treatment may be a more advantageous option compared to solely relying on systemic therapy.

[Analysis of O3 Pollution Affected by a Succession of Three Landfall Typhoons in 2020 in Eastern China].

Based on air quality monitoring, surface meteorological data, wind profile radar observation, and the HYSPLIT model, the characteristics and causes of O3 pollution in eastern China during the period of the typhoons BAVI, MAYSAK, and HAISHEN from August 26 to September 8, 2020 were analyzed. The results showed that during the succession of the three landfall typhoons, the O3 pollution sites in Beijing Tianjin Hebei and its surrounding areas (BTHS) and the Yangtze River Delta (YRD) exceeded 50%. During the HAISHEN period, O3 pollution days in the two regions reached 2.22 d and 2.97 d, respectively, with significant persistence characteristics. The location of the typhoon had an obvious influence on O3 concentration. When the typhoons were located within the 24h warning line, the O3 concentrations in BTHS and YRD were relatively low. When the typhoons were located between the 24 h and 48 h warning lines, the O3 concentration in BTHS was the highest. When the typhoons moved north of 34°N, the YRD was most prone to regional O3 pollution. O3 pollution in Shanghai mainly occurred under the control of the northward air flow to the west side of the typhoons, and the regional transport from the upstream area had a significant impact on the increase in O3 and its precursor concentrations. The downdraft below 1 000 m maintained O3 at a high concentration at night. In Jinan, O3 pollution mainly occurred under the control of the subtropical high and typhoon periphery. The downdraft prevailed in the middle and lower levels during the O3 pollution. From August 28 to 30, under the control of the subtropical high, the pollutants were mainly accumulated locally, and some of them were transmitted within the province, showing a "double high" phenomenon of O3 and PM2.5. From September 5 to 8, under the influence of HAISHEN peripheral circulation, the regional transport was obvious, and the O3 concentration increased earlier than that of PM2.5.

Type one autoimmune pancreatitis based on clinical diagnosis: A case report.

BACKGROUND: Autoimmune pancreatitis (AIP) is a rare form of autoimmune-mediated pancreatitis, which is easily misdiagnosed as pancreatic cancer and thus treated surgically. We studied the diagnosis and treatment of a patient with type 1 AIP recently admitted to our hospital, and reviewed the literature to provide a reference for clinical diagnosis of AIP. CASE SUMMARY: The chief complaint was yellowing of the body, eyes and urine for 21 d. The patient's clinical presentation was obstructive jaundice and imaging suggested pancreatic swelling. It was difficult to distinguish between inflammation and tumor. Serum immunoglobulin G4 (IgG4) was markedly elevated. IgG4 is an important serological marker for type 1 AIP. The patient was diagnosed with AIP, IgG4-related cholangitis, acute cholecystitis and hepatic impairment. After applying hormonal therapy, the patient's symptoms improved significantly. At the same time, imaging suggested that pancreatic swelling subsided, and liver function and other biochemical indicators decreased. The treatment was effective. CONCLUSION: In patients with pancreatic swelling, the possibility of AIP should be considered.

Design and assessment of a reconfigurable behavioral assistive robot: a pilot study.

Introduction: For patients with functional motor disorders of the lower limbs due to brain damage or accidental injury, restoring the ability to stand and walk plays an important role in clinical rehabilitation. Lower limb exoskeleton robots generally require patients to convert themselves to a standing position for use, while being a wearable device with limited movement distance. Methods: This paper proposes a reconfigurable behavioral assistive robot that integrates the functions of an exoskeleton robot and an assistive standing wheelchair through a novel mechanism. The new mechanism is based on a four-bar linkage, and through simple and stable conformal transformations, the robot can switch between exoskeleton state, sit-to-stand support state, and wheelchair state. This enables the robot to achieve the functions of assisted walking, assisted standing up, supported standing and wheelchair mobility, respectively, thereby meeting the daily activity needs of sit-to-stand transitions and gait training. The configuration transformation module controls seamless switching between different configurations through an industrial computer. Experimental protocols have been developed for wearable testing of robotic prototypes not only for healthy subjects but also for simulated hemiplegic patients. Results: The experimental results indicate that the gait tracking effect during robot-assisted walking is satisfactory, and there are no sudden speed changes during the assisted standing up process, providing smooth support to the wearer. Meanwhile, the activation of the main force-generating muscles of the legs and the plantar pressure decreases significantly in healthy subjects and simulated hemiplegic patients wearing the robot for assisted walking and assisted standing-up compared to the situation when the robot is not worn. Discussion: These experimental findings demonstrate that the reconfigurable behavioral assistive robot prototype of this study is effective, reducing the muscular burden on the wearer during walking and standing up, and provide effective support for the subject's body. The experimental results objectively and comprehensively showcase the effectiveness and potential of the reconfigurable behavioral assistive robot in the realms of behavioral assistance and rehabilitation training.

Thermal ablation for hepatic tumors in high-risk locations.

Thermal ablative techniques such as radiofrequency and microwave ablation are minimally invasive and cost-effective approaches that are currently being adopted as alternatives to surgical resection for primary and metastatic liver malignancies. However, they are considered to be relatively contraindicated for tumors in high-risk locations due to technical difficulties and a perceived increased risk of perioperative complications. Several techniques, including artificial ascites, non-touch multibipolar ablation, and laparoscopically assisted ablation, can be used to improve the outcomes of ablation for high-risk tumors. This review aims to provide a comprehensive summary of the techniques currently used to improve thermal ablation outcomes for high-risk liver tumors.

Balance recovery for lower limb exoskeleton in standing posture based on orbit energy analysis.

Introduction: The need for effective balance control in lower limb rehabilitation exoskeletons is critical for ensuring stability and safety during rehabilitation training. Current research into specialized balance recovery strategies is limited, highlighting a gap in biomechanics-inspired control methods. Methods: We introduce a new metric called "Orbit Energy" (OE), which assesses the balance state of the human-exoskeleton system based on the dynamics of the overall center of mass. Our control framework utilizes OE to choose appropriate balance recovery strategies, including torque controls at the ankle and hip joints. Results: The efficacy of our control algorithm was confirmed through Matlab Simulink simulations, which analyzed the recovery of balance under various disturbance forces and conditions. Further validation came from physical experiments with human subjects wearing the exoskeleton, where a significant reduction in muscle activation was observed during balance maintenance under external disturbances. Discussion: Our findings underscore the potential of biomechanics-inspired metrics like OE in enhancing exoskeleton functionality for rehabilitation purposes. The introduction of such metrics could lead to more targeted and effective balance recovery strategies, ultimately improving the safety and stability of exoskeleton use in rehabilitation settings.

Improving Hand Gesture Recognition Robustness to Dynamic Posture Variations by Multimodal Deep Feature Fusion.

Surface electromyography (sEMG), a human-machine interface for gesture recognition, has shown promising potential for decoding motor intentions, but a variety of nonideal factors restrict its practical application in assistive robots. In this paper, we summarized the current mainstream gesture recognition strategies and proposed a gesture recognition method based onmultimodal canonical correlation analysis feature fusion classification (MCAFC) for a nonideal condition that occurs in daily life, i.e., posture variations. The deep features of the sEMG and acceleration signals were first extracted via convolutional neural networks. A canonical correlation analysis was subsequently performed to associate the deep features of the two modalities. The transformed features were utilized as inputs to a linear discriminant analysis classifier to recognize the corresponding gestures. Both offline and real-time experiments were conducted on eight able-bodied subjects. The experimental results indicated that MCAFC achieved an average classification accuracy, average motion completion rate, and average motion completion time of 93.44%, 94.05%, and 1.38 s, respectively, with multiple dynamic postures, indicating significantly better performance than that of comparable methods. The results demonstrate the feasibility and superiority of the proposed multimodal signal feature fusion method for gesture recognition with posture variations, providing a new scheme for myoelectric control.

Deciphering the mitochondria-inflammation axis: Insights and therapeutic strategies for heart failure.

Heart failure (HF) is a clinical syndrome resulting from left ventricular systolic and diastolic dysfunction, leading to significant morbidity and mortality worldwide. Despite improvements in medical treatment, the prognosis of HF patients remains unsatisfactory, with high rehospitalization rates and substantial economic burdens. The heart, a high-energy-consuming organ, relies heavily on ATP production through oxidative phosphorylation in mitochondria. Mitochondrial dysfunction, characterized by impaired energy production, oxidative stress, and disrupted calcium homeostasis, plays a crucial role in HF pathogenesis. Additionally, inflammation contributes significantly to HF progression, with elevated levels of circulating inflammatory cytokines observed in patients. The interplay between mitochondrial dysfunction and inflammation involves shared risk factors, signaling pathways, and potential therapeutic targets. This review comprehensively explores the mechanisms linking mitochondrial dysfunction and inflammation in HF, including the roles of mitochondrial reactive oxygen species (ROS), calcium dysregulation, and mitochondrial DNA (mtDNA) release in triggering inflammatory responses. Understanding these complex interactions offers insights into novel therapeutic approaches for improving mitochondrial function and relieving oxidative stress and inflammation. Targeted interventions that address the mitochondria-inflammation axis hold promise for enhancing cardiac function and outcomes in HF patients.

Electrospinning Chitosan/Fe-Mn Nanofibrous Composite for Efficient and Rapid Removal of Arsenite from Water.

Efficient removal of extremely mobile and toxic As(III) from water is a challenging but critical task. Herein, we developed a functionalized sorbent of chitosan nanofiber with iron-manganese (Fe-Mn@CS NF) using a one-step hybrid electrospinning approach to remove trace As(III) from water. Batch adsorption studies were performed to determine the adsorption efficiency under a variety of conditions, including contact time, starting concentration of As(III), ionic strength, and the presence of competing anions. The experimental results demonstrated that the concentration of As(III) dropped from 550 to less than 1.2 µg/L when using 0.5 g/L Fe-Mn@CS NF. This demonstrates the exceptional adsorption efficiency (99.8%) of Fe-Mn@CS NF for removing As(III) at pH 6.5. The kinetic tests revealed that the adsorption equilibrium was reached in 2.6 h, indicating a quick uptake of As(III). The ionic strength effect analysis showed that the adsorbed As(III) formed inner-sphere surface complexes with Fe-Mn@CS NF. The presence of SO42- or F- had a negligible impact on As(III) uptake, while the presence of PO43- impeded As(III) absorption by competing for adsorption sites. The exhausted sorbent could be effectively regenerated with a dilute NaOH solution. Even after 10 cycles of regenerating Fe-Mn@CS NF, the adsorption efficiency of As(III) in natural groundwater was maintained over 65%. XPS and FTIR analyses show that the presence of M-OH and C-O groups on the sorbent surface is essential for removing As(III) from water. Overall, our study highlights the significant potential of Fe-Mn@CS NF for the efficient and quick elimination of As(III) from water.

Heterotopic mesenteric ossification caused by trauma: A case report.

BACKGROUND: Heterotopic mesenteric ossification (HMO) is a clinically rare condition characterized by the formation of bone tissue in the mesentery. The worldwide reporting of such cases is limited to just over 70 instances in the medical literature. The etiology of HMO remains unclear, but the disease is possibly induced by mechanical trauma, ischemia, or intra-left lower quadrant abdominal infection, leading to the differentiation of mesenchymal stem cells into osteoblasts. Here, we present a rare case of HMO that occurred in a 34-year-old male, who presented with left lower quadrant abdominal pain. CASE SUMMARY: We report the case of a 34-year-old male patient who presented with left lower abdominal pain following trauma to the left lower abdomen. He subsequently underwent surgical treatment, and the postoperative pathological diagnosis was HMO. CONCLUSION: We believe that although there is limited literature and research on HMO, when patients with a history of trauma or surgery to the left lower abdomen present with corresponding imaging findings, clinicians should be vigilant in distinguishing this condition and promptly selecting appropriate diagnostic and therapeutic interventions.

Calibration of the oscillation amplitude of quartz tuning fork-based force sensors with astigmatic displacement microscopy.

Quartz tuning forks and qPlus-based force sensors offer an alternative approach to silicon cantilevers for investigating tip-sample interactions in scanning probe microscopy. The high-quality factor (Q) and stiffness of these sensors prevent the tip from jumping to the contact, even at sub-nanometer amplitude. The qPlus configuration enables simultaneous scanning tunneling microscopy and atomic force microscopy, achieving spatial resolution and spectroscopy at the subatomic level. However, to enable precise measurement of tip-sample interaction forces, confidence in these measurements is contingent upon the accurate calibration of the spring constant and oscillation amplitude of the sensor. Here, we have developed a method called astigmatic displacement microscopy with picometer sensitivity.

RAD21 deficiency drives corneal to scleral differentiation fate switching via upregulating WNT9B.

The cornea and sclera are distinct adjacent tissues, yet their stromal cells originate from common neural crest cells (NCCs). Sclerocornea is a disease characterized by an indistinguishable boundary between the cornea and sclera. Previously, we identified a RAD21 mutation in a sclerocornea pedigree. Here, we investigated the impacts of RAD21 on NCC activities during eye development. RAD21 deficiency caused upregulation of PCDHGC3. Both RAD21 knockdown and PCDHGC3 upregulation disrupted the migration of NCCs. Transcriptome analysis indicated that WNT9B had 190.9-fold higher expression in scleral stroma than in corneal stroma. WNT9B was also significantly upregulated by both RAD21 knockdown and PCDHGC3 overexpression, and knock down of WNT9B rescued the differentiation and migration of NCCs with RAD21 deficiency. Consistently, overexpressing wnt9b in Xenopus tropicalis led to ocular developmental abnormalities. In summary, WNT9B is a determinant factor during NCC differentiation into corneal keratocytes or scleral stromal cells and is affected by RAD21 expression.

Disproportional signal of pericarditis with biological diseasemodifying antirheumatic drugs (bDMARDs) in patients with ankylosing spondylitis: a disproportionality analysis in the FAERS database.

Objective: This study aimed to investigate the potential association between biological disease-modifying antirheumatic drugs (bDMARDs) and pericarditis and uncover relevant clinical characteristics in ankylosing spondylitis (AS). Methods: Reports of pericarditis recorded in the FDA Adverse Event Reporting System (FAERS) (January 2004-December 2022) were identified through the preferred term "pericarditis." Demographic and clinical characteristics were described, and disproportionality signals were assessed through the reporting odds ratio (ROR) and information component (IC). A significant signal was detected if the lower bound of IC (IC025) was more than zero. Results: We found 1,874 reports of pericarditis with bDMARDs (11.3% of cases with fatal outcomes). Adalimumab (IC025 3.24), infliximab (IC025 4.90), golimumab (IC025 5.40), certolizumab (IC025 5.43), etanercept (IC025 3.24), secukinumab (IC025 3.97), and ustekinumab (IC025 7.61) exhibit significant disproportionality signals compared to other medications in the FAERS database. After excluding pre-existing diseases and co-treated drugs that may increase the susceptibility of pericarditis, the disproportionality signal associated with infliximab, certolizumab, etanercept, secukinumab, and ustekinumab remained strong. Pericarditis cases associated with all bDMARDs were predominantly recorded in women aged 25-65 years. Conclusion: More reports of pericarditis were detected with AS patients on bDMARDs than with other drugs in the overall database. Further studies are warranted to investigate the underlying mechanisms and identify patient-related susceptibility factors, thus supporting timely diagnosis and safe(r) prescribing of bDMARDs.

Factors affecting the effectiveness and safety of polymyxin B in the treatment of Gram-negative bacterial infections: A meta-analysis of 96 articles.

PURPOSE: Polymyxin B, with its unique structure and mechanism of action, has emerged as a key therapeutic agent against Gram-negative bacteria. The study aims to explore potential factors to influence its effectiveness and safety. METHODS: A model-based meta-analysis of 96 articles was conducted, focusing on factors like dosage, bacterial species, and combined antibiotic therapy. The analysis evaluated mortality rates and incidence rate of renal dysfunction, also employing parametric survival models to assess 30-d survival rates. RESULTS: In the study involving 96 articles and 9716 patients, polymyxin B's daily dose showed minimal effect on overall mortality, with high-dose group mortality at 33.57% (95% confidence intervals [CI]: 29.15-38.00) compared to the low-dose group at 35.44% (95% CI: 28.99-41.88), P = 0.64. Mortality significantly varied by bacterial species, with Pseudomonas aeruginosa infections at 58.50% (95% CI: 55.42-63.58). Monotherapy exhibited the highest mortality at 40.25% (95% CI: 34.75-45.76), P < 0.01. Renal dysfunction was more common in high-dose patients at 29.75% (95% CI: 28.52-30.98), with no significant difference across antibiotic regimens, P = 0.54. The 30-d overall survival rate for monotherapy therapy was 63.6% (95% CI: 59.3-67.5) and 70.2% (95% CI: 64.4-76.2) for association therapy with ß-lactam drugs. CONCLUSIONS: The dosage of polymyxin B does not significantly change death rates, but its effectiveness varies based on the bacterial infection. Certain bacteria like P. aeruginosa are associated with higher mortality. Combining polymyxin B with other antibiotics, especially ß-lactam drugs, improves survival rates. Side effects depend on the dose, with lower doses being safer. These findings emphasize the importance of customizing treatment to balance effectiveness and safety.

Abnormal expression of PRKAG2-AS1 in endothelial cells induced inflammation and apoptosis by reducing PRKAG2 expression.

PRKAG2 is required for the maintenance of cellular energy balance. PRKAG2-AS1, a long non-coding RNA (lncRNA), was found within the promoter region of PRKAG2. Despite the extensive expression of PRKAG2-AS1 in endothelial cells, the precise function and mechanism of this gene in endothelial cells have yet to be elucidated. The localization of PRKAG2-AS1 was predominantly observed in the nucleus, as revealed using nuclear and cytoplasmic fractionation and fluorescence in situ hybridization. The manipulation of PRKAG2-AS1 by knockdown and overexpression within the nucleus significantly altered PRKAG2 expression in a cis-regulatory manner. The expression of PRKAG2-AS1 and its target genes, PRKAG2b and PRKAG2d, was down-regulated in endothelial cells subjected to oxLDL and Hcy-induced injury. This finding suggests that PRKAG2-AS1 may be involved in the mechanism behind endothelial injury. The suppression of PRKAG2-AS1 specifically in the nucleus led to an upregulation of inflammatory molecules such as cytokines, adhesion molecules, and chemokines in endothelial cells. Additionally, this nuclear suppression of PRKAG2-AS1 facilitated the adherence of THP1 cells to endothelial cells. We confirmed the role of nuclear knockdown PRKAG2-AS1 in the induction of apoptosis and inhibition of cell proliferation, migration, and lumen formation through flow cytometry, TUNEL test, CCK8 assay, and cell scratching. Finally, it was determined that PRKAG2-AS1 exerts direct control over the transcription of PRKAG2 by its binding to their promoters. In conclusion, downregulation of PRKAG2-AS1 suppressed the proliferation and migration, promoted inflammation and apoptosis of endothelial cells, and thus contributed to the development of atherosclerosis resulting from endothelial cell injury.

Direct interaction of platelet with tumor cell aggravates hepatocellular carcinoma metastasis by activating TLR4/ADAM10/CX3CL1 axis.

Metastasis is the main culprit of cancer-related death and account for the poor prognosis of hepatocellular carcinoma. Although platelets have been shown to accelerate tumor cell metastasis, the exact mechanism remained to be fully understood. Here, we found that high blood platelet counts and increased tumor tissue ADAM10 expression indicated the poor prognosis of HCC patients. Meanwhile, blood platelet count has positive correlation with tumor tissue ADAM10 expression. In vitro, we revealed that platelet increased ADAM10 expression in tumor cell through TLR4/NF-κB signaling pathway. ADAM10 catalyzed the shedding of CX3CL1 which bound to CX3CR1 receptor, followed by inducing epithelial to mesenchymal transition and activating RhoA signaling in cancer cells. Moreover, knockdown HCC cell TLR4 (Tlr4) or inhibition of ADAM10 prevented platelet-increased tumor cell migration, invasion and endothelial permeability. In vivo, we further verified in mice lung metastatic model that platelet accelerated tumor metastasis via cancer cell TLR4/ADAM10/CX3CL1 axis. Overall, our study provides new insights into the underlying mechanism of platelet-induced HCC metastasis. Therefore, targeting the TLR4/ADAM10/CX3CL1 axis in cancer cells hold promise for the inhibition of platelet-promoted lung metastasis of HCC.