Search

Sepsis is a severe systemic infectious disease that often leads to multi-organ dysfunction. One of the common and serious complications of sepsis is renal injury. In this study, we aimed to investigate the potential mechanistic role of a novel compound called H-151 in septic kidney injury. We also examined its impact on renal function and mouse survival rates. Initially, we confirmed abnormal activation of the STING–TBK1 signaling pathway in the kidneys of septic mice. Subsequently, we treated the mice with H-151 and observed significant improvement in sepsis-induced renal dysfunction. This was evidenced by reductions in blood creatinine and urea nitrogen levels, as well as a marked decrease in inflammatory cytokine levels. Furthermore, H-151 substantially improved the seven-day survival rate of septic mice, indicating its therapeutic potential. Importantly, H-151 also exhibited an inhibitory effect on renal apoptosis levels, further highlighting its mechanism of protecting against septic kidney injury. These study findings not only offer new insights into the treatment of septic renal injury but also provide crucial clues for further investigations into the regulatory mechanisms of the STING–TBK1 signaling pathway and potential drug targets.

In the system-level simulations of heat transfer systems, the characteristics of heat exchangers are often considered constant or used in empirical formulas, which affect the accuracy of the system model. Herein a multi-scale simulation method to analyze the heat transfer characteristics of a thermal management system, including an intermediate loop is proposed. The system model is developed based on the heat current method and flow resistance models. By applying COMSOL LiveLink for MATLAB module, a multi-scale model is obtained, which combines three-dimensional numerical models of the heat exchangers with the system model. Compared to the experimental results, the relative errors associated with the outlet temperatures and heat transfer rate are less than 1.1% and 8.2 %, respectively, thus validating the model. Discussions on the effects of the geometric structure of the heat exchangers on the system show that a plate heat exchanger with 12 plates and a plate spacing of 8 mm is better. For achieving systematic maximum heat dissipation for a certain pumping power consumption, a multi-scale optimization method is proposed by coupling the Lagrange function and numerical model. The results show that the total heat transfer rate improves by 5.89 %, from 8314.81 W to 8804.35 W.

Abstract Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection.

Alzheimer’s disease (AD) is recognized as the leading cause of dementia, imposing a significant economic toll on society. Despite the emergence of novel therapeutic approaches for AD, their efficacy and safety mandates further validation through rigorous clinical trials. In this context, hypertension (HTN) has garnered considerable attention as an amendable risk factor for AD. Research indicates that hypertension during midlife is associated with an elevated risk of AD in later years, influencing both the onset and progression of the disease. Nevertheless, the relationship between AD and hypertension in the later stages of life remains a subject of debate. Moreover, the consequences of blood pressure reduction on cognitive function, along with the optimal pharmacological interventions and therapeutic thresholds for hypertension, have emerged as pivotal areas of inquiry. This review synthesizes findings on epidemiology, neuroimaging, and biomarkers, and the effects of antihypertensive medications to elucidate the link between hypertension and cognitive performance. We particularly investigate how hypertension and AD are related by plasma sulfide dysregulation, offering possible indicators for future diagnosis and therapy.

AbstractIntroduction The tissue stiffness of donor kidneys in transplantation may increase due to pathological changes such as glomerulosclerosis and interstitial fibrosis, and those changes associate worse outcomes in kidney transplantation recipients. Ultrasound elastography is a noninvasive imaging examination with the ability to quantitatively reflect tissue stiffness. Aim of this study was to evaluate the prognostic value of ultrasound elastography for adverse kidney outcome in kidney transplantation recipients.Methods Shear wave elastography (SWE) examinations were performed by two independent operators in kidney transplantation recipients. The primary outcome was a composite of kidney graft deterioration, all-cause re-hospitalization, and all-cause mortality. Survival analysis was calculated by Kaplan-Meier curves with the log-rank test and Cox regression analysis.Results A total of 161 patients (mean age 46 years, 63.4% men) were followed for a median of 20.1 months. 27 patients (16.77%) reached the primary endpoint. The mean and median tissue stiffness at the medulla (hazard ratio: 1.265 and 1.229, respectively), estimated glomerular filtration rate (eGFR), and serum albumin level were associated with the primary outcome in univariate Cox regression. Adding mean or median medulla SWE to a baseline model containing eGFR and albumin significantly improved its discrimination (C-statistics: 0.736 for the baseline, 0.766 and 0.772 for the model added mean and median medulla SWE, respectively).Conclusion The medullary tissue stiffness of kidney allograft measured by shear wave elastography may provide incremental prognostic value to adverse outcomes in kidney transplantation recipients. Including SWE parameters in kidney transplantation recipients management could be considered to improve risk stratification.

Electromagnetic interference poses a significant challenge to the reliability and performance of electronic equipment, particularly in the aerospace and aviation sectors where the demand for high-performance electromagnetic shielding materials is paramount. This study introduces an innovative solution: a lightweight nickel-plated carbon fiber composite chassis, designed to meet these stringent requirements. Through comparative analysis, we prove that this composite chassis is not only comparable to traditional metal chassis in terms of time-domain shielding effect, but also close to traditional metal chassis in terms of heat dissipation capability. Notably, it achieves a substantial weight reduction of 71.43% to 76.25% compared to its metal counterparts, addressing the critical need for lighter materials in aerospace applications. The superior heat dissipation feature of the nickel-plated carbon fiber composite, quantitatively superior to conventional materials, indicates its potential to enhance the operational efficiency and safety of aerospace electronics. This research underscores the viability of nickel-plated carbon fiber composites as a groundbreaking material for electromagnetic shielding, promising significant advancements in aerospace and beyond.

Abstract Tumor mRNA vaccines have been developed for over 20 years. Whether mRNA vaccines could promote a clinical benefit to advanced cancer patients is highly unknown. PubMed and Embase were retrieved from January 1, 2000 to January 4, 2023. Random effects models were employed. Clinical benefit (objective response rate [ORR], disease control rate [DCR], 1‐year/2‐year progression‐free survival [PFS], and overall survival [OS]) and safety (vaccine‐related grade 3–5 adverse events [AEs]) were evaluated. Overall, 984 patients (32 trials) were enrolled. The most typical cancer types were melanoma (13 trials), non‐small cell lung cancer (5 trials), renal cell carcinoma (4 trials), and prostate adenocarcinoma (4 trials). The pooled ORR and DCR estimates were 10.0% (95%CI, 4.6–17.0%) and 34.6% (95%CI, 24.1–45.9%). The estimates for 1‐year and 2‐year PFS were 38.4% (95%CI, 24.8−53.0%) and 20.0% (95%CI, 10.4–31.7%), respectively. The estimates for 1‐year and 2‐year OS were 75.3% (95%CI, 62.4–86.3%) and 45.5% (95%CI, 34.0–57.2%), respectively. The estimate for vaccine‐related grade 3–5 AEs was 1.0% (95%CI, 0.2–2.4%). Conclusively, mRNA vaccines seem to demonstrate modest clinical response rates, with acceptable survival rates and rare grade 3–5 AEs.

Chiral aliphatic amine and alcohol derivatives are difficult to access due to the challenge to differentiate between spatially and electronically similar alkyl groups. Here the authors show a nickel-catalyzed enantioselective hydroalkylation of acyl enamines and enol esters with alkyl halides to afford enantioenriched α-branched aliphatic acyl amines and esters in good yields with excellent enantioselectivity.

Abstract Fibrotic tissue remodelling in nonalcoholic fatty liver disease (NAFLD) will probably emerge as the leading cause of end-stage liver disease in the coming decades, but the ability to diagnose liver fibrosis in NAFLD patients noninvasively is limited. The abnormal expression of tRNA-derived small RNA (tsRNA) in plasma provides a novel idea for noninvasive diagnosis of various diseases, however, the relationship between tsRNAs and NAFLD is still unknown. Here, we took advantage of small RNA-Seq technology to profile tsRNAs in NAFLD patients and found the ubiquitous presence of hepatic tsRNAs secreted into circulating blood. Verification in a cohort of 114 patients with NAFLD and 42 patients without NAFLD revealed that three tsRNAs (tRF-Val-CAC-005, tiRNA-His-GTG-001, and tRF-Ala-CGC-006) were significantly elevated in the plasma of NAFLD patients, and the expression level are associated with NAFLD activity score (calculated from 0 to 8) and fibrosis stage (scored from 0 to 4). In mouse models, we further found that increased plasma levels of these three tsRNAs were positively correlated with the degree of liver fibrosis. Our study potentially identifies a new class of NAFLD biomarkers and reveal the possible existence of tsRNAs in the blood that can be used to predict fibrogenesis risk in patients diagnosed with NAFLD.

The incidence of systemic fungal infection is increasing, and millions of people around the world suffer from fungal infections. Candida albicans is one of the most frequently isolated fungal pathogens in clinical settings. As a polymorphic organism, the transition between yeast and hyphae is critical for C. albicans virulence and pathogenesis. However, the mechanism of hyphae-associated virulence remains unclear. Candidalysin is the first human fungal cytolytic peptide toxin originating from the hyphae-specific gene, ECE1. This review will summarize the most recent progress underlying candidalysin-mediated epithelial damage and host defense pathways, which might shed new light on the development of a novel antifungal strategy and early diagnostic biomarker.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune-mediated idiopathic inflammatory demyelinating disease with a typical clinical presentation of optic neuritis, acute myelitis, and area postrema syndrome. Most NMOSD patients are seropositive for disease-specific and pathogenic aquaporin-4 (AQP4) antibodies, which are key markers for the NMOSD diagnosis. Herein, we report an atypical case of a 41-year-old man who complained of intractable hiccups and vomiting at disease onset, followed by fever, headache, back pain, progressive paresthesia, and weakness of extremities later on. Magnetic resonance imaging revealed longitudinally extensive transverse myelitis. Cerebrospinal fluid analysis showed progressive increases in the white blood cell count and the protein level, which were accompanied by the deterioration of clinical manifestations. The patient was initially suspected of infectious meningomyelitis but was finally diagnosed with NMOSD. This case with distinct cerebrospinal fluid findings broadens the phenotypic spectrum of NMOSD. Furthermore, it also highlights the clinical value of AQP4 antibody test for early definitive diagnosis and proper treatment.

Aluminum alloys have excellent properties such as low density and high strength-to-weight ratio. However, the negative standard electrode potential of aluminum leads to a more active chemical property and is prone to corrode; as a result, the poor corrosion resistance extremely limits the widespread application of aluminum. Therefore, it is necessary to take appropriate measures to improve the poor corrosion resistance of aluminum alloys. The chromate passivation technology is one of the most effective and mature aluminum alloy surface treatment technologies, and even if the formed passivation film is very thin, it can still greatly enhance the corrosion resistance of aluminum alloys and provide corrosion protection. However, Cr (VI) and its derivatives are highly toxic and carcinogenic, and they are harmful to the environment and the human body. As environmental awareness increases and the government strictly limits the use and emission of chromate, it is necessary to develop new treatments that are environmentally friendly and non-toxic to improve the corrosion resistance of aluminum alloys. The fabrication process of layered double hydroxides (LDHs) film is simple, and the morphology of the LDHs film can be controlled by adjusting the experimental parameters. The prepared LDHs film also has good corrosion resistance and anions exchange performance. Therefore, reports of in-situ growth LDHs film on the surface aluminum alloys have gradually increased in recent years. In this paper, we introduced a variety of methods for preparing LDHs film, such as ordinary hydrothermal, urea hydrolysis, and hexamethylenetetramine hydrolysis methods, and summarized the effects of different experimental conditions on the morphology and corrosion resistance of LDHs the films. Several commonly used modification methods and principles, such as the preparation of superhydrophobic films and self-healing films, were discussed in detail and the limitations of the current research were discussed. Finally, the focus of future research and development were described.

Kai-Xin-San consists of Ginseng Radix, Polygalae Radix, Acori Tatarinowii Rhizoma, and Poria at a ratio of 3:3:2:2. Kai-Xin-San has been widely used for the treatment of emotional disorders in China. However, no studies have identified the key proteins implicated in response to Kai-Xin-San treatment. In this study, rat models of chronic mild stress were established using different stress methods over 28 days. After 14 days of stress stimulation, rats received daily intragastric administrations of 600 mg/kg Kai-Xin-San. The sucrose preference test was used to determine depression-like behavior in rats, while isobaric tags were used for relative and absolute quantitation-based proteomics to identify altered proteins following Kai-Xin-San treatment. Kai-Xin-San treatment for 2 weeks noticeably improved depression-like behaviors in rats with chronic mild stress. We identified 33 differentially expressed proteins: 7 were upregulated and 26 were downregulated. Functional analysis showed that these differentially expressed proteins participate in synaptic plasticity, neurodevelopment, and neurogenesis. Our results indicate that Kai-Xin-San has an important role in regulating the key node proteins in the synaptic signaling network, and are helpful to better understand the mechanism of the antidepressive effects of Kai-Xin-San and to provide objective theoretical support for its clinical application. The study was approved by the Ethics Committee for Animal Research from the Chinese PLA General Hospital (approval No. X5-2016-07) on March 5, 2016.

Tannic acid (TA) is widely used to protect metals from corrosion because it is environmentally friendly and inexpensive. However, the single effect of TA used as corrosion inhibitor has been widely investigated and studies focusing on the corrosion inhibition effect have been limited. Some studies have proven that the addition of a compound corrosion inhibitor can considerably improve the corrosion inhibition efficiency of an inhibitor, and this method can be applied to TA. The corrosion inhibition effect of the combination of two compounds, FeCl3 and Na2MoO4, with TA was analyzed on carbon steel Q235. Copper sulfate drip test, soaking test, and electrochemical test were used to compare the film-forming characteristics and corrosion inhibition effect of the combination of FeCl3 and Na2MoO4 with TA on carbon steel surface. The discoloration time of copper sulfate droplets initially increases and subsequently decreases with the increase in the concentrations of FeCl3 and Na2MoO4 in TA. At the end of the soaking test, fewer pits are observed on the surface of carbon steel following the addition of FeCl3 and Na2MoO4 to the TA inhibitor. Based on the results of the electrochemical tests, the corrosion inhibition effects of the TA inhibitor on carbon steel before and after the addition of FeCl3 were compared. The results reveal that the charge transfer resistance of the two inhibitors increases from 2698 to 3711 Ω·cm2, and the corrosion current density decreases from 2.734 to 1.902 μA·cm−2. A clear increase and decrease in the charge transfer resistance and corrosion current density, respectively, are observed once Na2MoO4 is added. Further, the charge transfer resistance increases from 2698 to 5100 Ω·cm2, and the corrosion current density decreases from 2.734 to 0.714 μA·cm−2. The following conclusions can be drawn from these results: the addition of FeCl3 or Na2MoO4 to TA can both improve the corrosion inhibition effect of TA; the compound system of TA and Na2MoO4 exhibits a better corrosion inhibition effect compared with the compound system of TA and FeCl3.

ObjectiveThe aim of this study was to explore the protective effects and the regulatory mechanisms of bariatric surgery on kidney injury in diabetic rats.MethodsWe established a useful type 2 diabetic rat model using high-fat and high-sugar diet feeding following low-dose streptozotocin (STZ) treatment. Sprague–Dawley (SD) rats were randomly divided into the following groups: control (Con) group, diabetic nephropathy (DN) group, and duodenal–jejunal bypass (DJB) surgery group. The food intake and body weight of rats were monitored and the glucose tolerance test (OGTT) test was performed every 2 weeks. The glomerular filtration rate (GFR) and urinary albumin excretion rate (UAFR) were measured to assess renal function. Hematoxylin–eosin (H&E), periodic acid–Schiff (PAS), and Masson staining were used to evaluate renal histopathological changes. TUNEL assay was performed to detect cell apoptosis. The expressions of oxidative stress factors and inflammatory factors in the renal tissues of rats were detected by ELISA. The expressions of PPARα, reactive oxygen species (ROS), and NF-κB were detected by immunofluorescence. For in vitro experiment, HK2 cells cultured with high glucose were treated with PPARα agonist, PPARα antagonist, and adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) agonist. The expressions of AMPK/PPARα/NF-κB signaling pathway-related proteins were detected by Western blot.ResultsBariatric surgery improved the glucose tolerance of DN rats. The GFR was decreased, the promotion of urinary albumin excretion rate (UAER) was inhibited, and the renal injury was alleviated. The extracellular matrix fraction was decreased and the renal function was improved. Meanwhile, bariatric surgery activates PPARα, inhibits ROS release, reduces oxidative stress injury, and reduces renal cell apoptosis. In vitro experiment results showed that the AMPK activator could activate PPARα, downregulate NF-κB, and inhibit inflammatory response. The phosphorylation of AMPK was inhibited by PPARα antagonism.ConclusionBariatric surgery can activate PPARα, inhibit oxidative stress injury, and improve glucose metabolism and renal function in DN rats.

Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis, a rare subtype of autoimmune encephalitis, was first reported by Lai et al. The AMPAR antibodies target against extracellular epitopes of the GluA1 or GluA2 subunits of the receptor. AMPARs are expressed throughout the central nervous system, especially in the hippocampus and other limbic regions. Anti-AMPAR encephalitis was more common in middle-aged women and most patients had an acute or subacute onset. Limbic encephalitis, a classic syndrome of anti-AMPAR encephalitis, was clinically characterized by a subacute disturbance of short-term memory loss, confusion, abnormal behavior and seizure. Magnetic resonance imaging often showed T2/fluid-attenuated inversion-recovery hyperintensities in the bilateral medial temporal lobe. For suspected patients, paired serum and cerebrospinal fluid (CSF) testing with cell-based assay were recommended. CSF specimen was preferred given its higher sensitivity. Most patients with anti-AMPAR encephalitis were complicated with tumors, such as thymoma, small cell lung cancer, breast cancer, and ovarian cancer. First-line treatments included high-dose steroids, intravenous immunoglobulin and plasma exchange. Second-line treatments, including rituximab and cyclophosphamide, can be initiated in patients who were non-reactive to first-line treatment. Most patients with anti-AMPAR encephalitis showed a partial neurologic response to immunotherapy.

Chronic myeloid leukemia (CML) is a malignant tumor caused by the abnormal proliferation of hematopoietic stem cells. Among a new series of acridone derivatives previously synthesized, it was found that the methoxybenzyl 5-nitroacridone derivative 8q has nanomolar cytotoxicity in vitro against human chronic myelogenous leukemia K562 cells. In order to further explore the possible anti-leukemia mechanism of action of 8q on K562 cells, a metabolomics and molecular biology study was introduced. It was thus found that most of the metabolic pathways of the G1 phase of K562 cells were affected after 8q treatment. In addition, a concentration-dependent accumulation of cells in the G1 phase was observed by cell cycle analysis. Western blot analysis showed that 8q significantly down-regulated the phosphorylation level of retinoblastoma-associated protein (Rb) in a concentration-dependent manner, upon 48 h treatment. In addition, 8q induced K562 cells apoptosis, through both mitochondria-mediated and exogenous apoptotic pathways. Taken together, these results indicate that 8q effectively triggers G1 cell cycle arrest and induces cell apoptosis in K562 cells, by inhibiting the CDK4/6-mediated phosphorylation of Rb. Furthermore, the possible binding interactions between 8q and CDK4/6 protein were clarified by homology modeling and molecular docking. In order to verify the inhibitory activity of 8q against other chronic myeloid leukemia cells, KCL-22 cells and K562 adriamycin-resistant cells (K562/ADR) were selected for the MTT assay. It is worth noting that 8q showed significant anti-proliferative activity against these cell lines after 48 h/72 h treatment. Therefore, this study provides new mechanistic information and guidance for the development of new acridones for application in the treatment of CML.

In this study, bio-based poly(lactic acid) (PLA)/polycaprolactone (PCL) blends and PLA/PCL/silicon carbide (SiC) composites were prepared using a solution blending method. The surface of the SiC whiskers was modified using a silane coupling agent. The effects of the PCL and SiC contents on the flexural properties, fracture toughness, morphology of PLA/PCL blends, and PLA/PCL/SiC composites were investigated using several techniques. Both the fracture toughness and flexural strength of PLA increased by the introduction of PCL and were further improved by the formation of SiC whiskers. Fracture surfaces were observed by scanning electron microscopy, which showed that the use of PCL as a reinforcing agent induces plastic deformation in the PLA/PCL blends. The SiC whiskers absorbed external energy because of their good interfacial adhesion with the PLA matrix and through SiC-PLA debonding in the PLA/PCL/SiC composites.

Consolidated memory can re-enter states of transient instability following reactivation, which is referred to as reconsolidation, and the exact molecular mechanisms underlying this process remain unexplored. Brain-derived neurotrophic factor (BDNF) plays a critical role in synaptic plasticity and memory processes. We have recently observed that BDNF signaling in the central nuclei of the amygdala (CeA) and insular cortex (IC) was involved in the consolidation of conditioned taste aversion (CTA) memory. However, whether BDNF in the CeA or IC is required for memory reconsolidation is still unclear. In the present study, using a CTA memory paradigm, we observed increased BDNF expression in the IC but not in the CeA during CTA reconsolidation. We further determined that BDNF synthesis and signaling in the IC but not in the CeA was required for memory reconsolidation. The differential, spatial-specific roles of BDNF in memory consolidation and reconsolidation suggest that dissociative molecular mechanisms underlie reconsolidation and consolidation, which might provide novel targets for manipulating newly encoded and reactivated memories without causing universal amnesia.

Methane has shown protective effects on a variety of diseases. Among these, neurological diseases have attracted much attention. However, there are many different indicators and application methods of methane in the treatment of neurological diseases. In this review, we summarize the indicators related to the protective effects of methane and evaluate the preparation and administration of methane. Thus, we hope to offer available indicators and effective ways to produce and administer methane in future research. [ABSTRACT FROM AUTHOR]