Ramelteon protects against social defeat stress-associated abnormal behaviors.

Psychological stress affects the neuroendocrine regulation, which modulates mental status and behaviors. Melatonin, a hormone synthesized primarily by the pineal gland, regulates many brain functions, including circadian rhythms, pain, sleep, and mood. Selective pharmacological melatonin agonist ramelteon has been clinically used to treat mood and sleep disorders. Posttraumatic stress disorder (PTSD) is a psychiatric condition associated with severe trauma; it is generally triggered by traumatic events, which lead to severe anxiety and uncontrollable trauma recall. We recently reported that repeated social defeat stress (RSDS) may induce robust anxiety-like behaviors and social avoidance in mice. In the present study, we investigated whether melatonin receptor activation by melatonin and ramelteon regulates RSDS-induced behavioral changes. Melatonin treatment improved social avoidance and anxiety-like behaviors in RSDS mice. Moreover, treatment of the non-selective MT1/MT2 receptor agonist, ramelteon, markedly ameliorated RSDS-induced social avoidance and anxiety-like behaviors. Moreover, activating melatonin receptors also balanced the expression of monoamine oxidases, glucocorticoid receptors, and endogenous antioxidants in the hippocampus. Taken together, our findings indicate that the activation of both melatonin and ramelteon regulates RSDS-induced anxiety-like behaviors and PTSD symptoms. The current study also showed that the regulatory effects of neuroendocrine mechanisms and cognitive behaviors on melatonin receptor activation in repeated social defeat stress.

Construction of Magnesium Phosphate Chemical Conversion Coatings with Different Microstructures on Titanium to Enhance Osteogenesis and Angiogenesis.

Titanium (Ti) and its alloys are widely used as hard tissue substitutes in dentistry and orthopedics, but their low bioactivity leads to undesirable osseointegration defects in the early osteogenic phase. Surface modification is an important approach to overcome these problems. In the present study, novel magnesium phosphate (MgP) coatings with controllable structures were fabricated on the surface of Ti using the phosphate chemical conversion (PCC) method. The effects of the microstructure on the physicochemical and biological properties of the coatings on Ti were researched. The results indicated that accelerators in PCC solution were important factors affecting the microstructure and properties of the MgP coatings. In addition, the coated Ti exhibited excellent hydrophilicity, high bonding strength, and good corrosion resistance. Moreover, the biological results showed that the MgP coatings could improve the spread, proliferation, and osteogenic differentiation of mouse osteoblast cells (MC3T3-E1) and vascular differentiation of human umbilical vein endothelial cells (HUVECs), indicating that the coated Ti samples had a great effect on promoting osteogenesis and angiogenesis. Overall, this study provided a new research idea for the surface modification of conventional Ti to enhance osteogenesis and angiogenesis in different bone types for potential biomedical applications.

Predictive Model to Identify the Long Time Survivor in Patients with Glioblastoma: A Cohort Study Integrating Machine Learning Algorithms.

We aimed to develop and validate a predictive model for identifying long-term survivors (LTS) among glioblastoma (GB) patients, defined as those with an overall survival (OS) of more than 3 years. A total of 293 GB patients from CGGA and 169 from TCGA database were assigned to training and validation cohort, respectively. The differences in expression of immune checkpoint genes (ICGs) and immune infiltration landscape were compared between LTS and short time survivor (STS) (OS<1.5 years). The differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were used to identify the genes differentially expressed between LTS and STS. Three different machine learning algorithms were employed to select the predictive genes from the overlapping region of DEGs and WGCNA to construct the nomogram. The comparison between LTS and STS revealed that STS exhibited an immune-resistant status, with higher expression of ICGs (P<0.05) and greater infiltration of immune suppression cells compared to LTS (P<0.05). Four genes, namely, OSMR, FMOD, CXCL14, and TIMP1, were identified and incorporated into the nomogram, which possessed good potential in predicting LTS probability among GB patients both in the training (C-index, 0.791; 0.772-0.817) and validation cohort (C-index, 0.770; 0.751-0.806). STS was found to be more likely to exhibit an immune-cold phenotype. The identified predictive genes were used to construct the nomogram with potential to identify LTS among GB patients.

Ultrasound-driven facile fabrication of Pd doped SnO2 hierarchical superstructures: Structural, growth mechanism, dermatoglyphics, and anti-cancer activity.

This research introduces a novel method that leverages Spirulina extract (S.E) as a bio-surfactant in the ultrasound-assisted synthesis (UAS) of Pd3+ (0.25-10 mol%) doped tin oxide (SnO2) self-assembled superstructures. Nanotechnology has witnessed significant advancements in recent years, driven by the exploration of novel synthesis methods and the development of advanced nanomaterials tailored for specific applications. Metal oxide nanoparticles, particularly SnO2, have garnered considerable attention due to their versatile properties and potential applications in various fields, including gas sensing, catalysis, and biomedical engineering. The study explores how varying influential parameters like S.E concentration, sonication time, pH, and sonication power can influence the resulting superstructures' morphology, size, and shape. A theoretical model for forming different hierarchical superstructures (HS) is proposed. X-ray diffraction (XRD) analysis confirms the crystalline tetragonal rutile phase of the SnO2:Pd HS. Raman spectroscopy reveals a red shift in the A1g mode, indicating phonon confinement due to various defects in the SnO2 structure. Further characterization using transmission electron microscopy (TEM), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS) provides insights into particle size, surface morphology, elemental composition, and binding energy. The study also demonstrates the application of optimized SnO2:3Pd HS in developing latent fingerprints (LFPs) on different surfaces using a simple powder dusting (PD) method, with the fingerprints (FPs) visualized under normal light. A mathematical model developed in Python-based software is used to analyze various features of the developed FPs, including pore properties such as number, position, inter-spacing, area, and shape. Additionally, an in vitro MTT assay shows concentration-dependent anticancer activity of SnO2:3Pd nanoparticles (NPs) on MCF7 cell lines, highlighting their potential as a promising cancer treatment option. Overall, the study suggests that the optimized HS can serve as multifunctional platforms for biomedical and dermatoglyphics applications, demonstrating the versatility and potential of the synthesized materials.

[Microtubule-associated tumor suppressor 1 inhibits hemin-induced apoptosis of vascular endothelial cells via hemeoxygenase 1].

This study aimed to investigate the effects of microtubule associated tumor suppressor 1 (MTUS1) on hemeoxygenase 1 (HMOX1) expression and hemin-induced apoptosis of vascular endothelial cells and its regulatory mechanism. RNA sequencing, RT-qPCR and Western blot were used to assess altered genes of hemin binding proteins, the expression of cAMP response element-binding protein (CREB) and nuclear respiratory factor 2 (NRF2), hemin-induced HMOX1 expression in MTUS1 knockdown human umbilical vein endothelial cells (HUVEC), and the effect of overexpression of CREB and NRF2 on HMOX1 expression in MTUS1 knockdown 293T cells. The effect of MTUS1 or HMOX1 knockdown on hemin-induced apoptosis in HUVEC, and the overexpression of NRF2 on hemin-induced apoptosis in MTUS1 knockdown 293T cells were assayed with CCK8 and Western blot. The results showed that MTUS1 was knocked down significantly in HUVEC by siRNA (P < 0.01), accompanied by decreased HMOX1 expression (P < 0.01). The increased HMOX1 expression induced by hemin was also inhibited by MTUS1 knockdown (P < 0.01). And the apoptosis of HUVEC induced by hemin was amplified by MTUS1 or HMOX1 knockdown (P < 0.01). Moreover the expression of CREB and NRF2 were both inhibited by MTUS1 knockdown in HUVEC (P < 0.01). The decreased HMOX1 regulated by MTUS1 knockdown could be rescued partly by overexpression of NRF2 (P < 0.01), however, not by overexpression of CREB. And the MTUS1 knockdown mediated decreased 293T cells viability induced by hemin could be partly rescued by NRF2 overexpression (P < 0.01). These results suggest that MTUS1 can inhibit hemin-induced apoptosis of HUVEC, and the mechanism maybe related to MTUS1/NRF2/HMOX1 pathway.

Biopsy forceps are useful for measuring esophageal varices in vitro.

BACKGROUND: To avoid acute variceal bleeding in cirrhosis, current guidelines recommend screening for high-risk esophageal varices (EVs) by determining variceal size and identifying red wale markings. However, visual measurements of EV during routine endoscopy are often inaccurate. AIM: To determine whether biopsy forceps (BF) could be used as a reference to improve the accuracy of binary classification of variceal size. METHODS: An in vitro self-made EV model with sizes ranging from 2 to 12 mm in diameter was constructed. An online image-based survey comprising 11 endoscopic images of simulated EV without BF and 11 endoscopic images of EV with BF was assembled and sent to 84 endoscopists. The endoscopists were blinded to the actual EV size and evaluated the 22 images in random order. RESULTS: The respondents included 48 academic and four private endoscopists. The accuracy of EV size estimation was low in both the visual (13.81%) and BF-based (20.28%) groups. The use of open forceps improved the ability of the endoscopists to correctly classify the varices by size (small ≤ 5 mm, large > 5 mm) from 71.85% to 82.17% (P < 0.001). CONCLUSION: BF may improve the accuracy of EV size assessment, and its use in clinical practice should be investigated.

LPS priming-induced immune tolerance mitigates LPS-stimulated microglial activation and social avoidance behaviors in mice.

In this study, we investigated the regulatory mechanisms underlying the effects of LPS tolerance on the inflammatory homeostasis of immune cells. LPS priming-induced immune tolerance downregulated cyclooxygenase-2, and lowered the production of prostaglandin-E2 in microglial cells. In addition, LPS tolerance downregulated the expression of suppressor of cytokine signaling 3, and inducible nitric oxide synthase/nitric oxide; suppressed the LPS-mediated induction of tumor necrosis factor-α, interleukin (IL)-6, and IL-1; and reduced reactive oxygen species production in microglial cells. LPS stimulation increased the levels of the adaptive response-related proteins heme oxygenase-1 and superoxide dismutase 2, and the levels of heme oxygenase-1 (HO-1) enhanced after LPS priming. Systemic administration of low-dose LPS (0.5 mg/kg) to mice for 4 consecutive days attenuated high-dose LPS (5 mg/kg)-induced inflammatory response, microglial activation, and proinflammatory cytokine expression. Moreover, repeated exposure to low-dose LPS suppressed the recruitment of peripheral monocytes or macrophages to brain regions and downregulated the expression of proinflammatory cytokines. Notably, LPS-induced social avoidance behaviors in mice were mitigated by immune tolerance. In conclusion, immune tolerance may reduce proinflammatory cytokine expression and reactive oxygen species production. Our findings provide insights into the effects of endotoxin tolerance on innate immune cells and social behaviors.

Bile duct ligation elevates 5-HT levels in cerebral cortex of rats partly due to impairment of brain UGT1A6 expression and activity via ammonia accumulation.

Hepatic encephalopathy (HE) is often associated with endogenous serotonin (5-HT) disorders. However, the reason for elevated brain 5-HT levels due to liver failure remains unclear. This study aimed to investigate the mechanism by which liver failure increases brain 5-HT levels and the role in behavioral abnormalities in HE. Using bile duct ligation (BDL) rats as a HE model, we verified the elevated 5-HT levels in the cortex but not in the hippocampus and striatum, and found that this cortical 5-HT overload may be caused by BDL-mediated inhibition of UDP-glucuronosyltransferase 1A6 (UGT1A6) expression and activity in the cortex. The intraventricular injection of the UGT1A6 inhibitor diclofenac into rats demonstrated that the inhibition of brain UGT1A6 activity significantly increased cerebral 5-HT levels and induced HE-like behaviors. Co-immunofluorescence experiments demonstrated that UGT1A6 is primarily expressed in astrocytes. In vitro studies confirmed that NH4Cl activates the ROS-ERK pathway to downregulate UGT1A6 activity and expression in U251 cells, which can be reversed by the oxidative stress antagonist N-acetyl-l-cysteine and the ERK inhibitor U0126. Silencing Hepatocyte Nuclear Factor 4α (HNF4α) suppressed UGT1A6 expression whilst overexpressing HNF4α increased Ugt1a6 promotor activity. Meanwhile, both NH4Cl and the ERK activator TBHQ downregulated HNF4α and UGT1A6 expression. In the cortex of hyperammonemic rats, we also found activation of the ROS-ERK pathway, decreases in HNF4α and UGT1A6 expression, and increases in brain 5-HT content. These results prove that the ammonia-mediated ROS-ERK pathway activation inhibits HNF4α expression to downregulate UGT1A6 expression and activity, thereby increasing cerebral 5-HT content and inducing manic-like HE symptoms. This is the first study to reveal the mechanism of elevated cortical 5-HT concentration in a state of liver failure and elucidate its association with manic-like behaviors in HE.

Comparing tocilizumab biosimilar BAT1806/BIIB800 with reference tocilizumab in patients with moderate-to-severe rheumatoid arthritis with an inadequate response to methotrexate: a phase 3, randomised, multicentre, double-blind, active-controlled clinical trial.

BACKGROUND: Biosimilars provide an opportunity to address unmet medical need by expanding access to biological treatments. This study aimed to show equivalent efficacy, and comparable safety, immunogenicity, and pharmacokinetic profiles of a proposed tocilizumab biosimilar BAT1806/BIIB800, to reference tocilizumab, in participants with rheumatoid arthritis with an inadequate response to methotrexate. METHODS: This phase 3, multicentre, randomised, double-blind, active-controlled, equivalence study comprised a 24-week initial treatment period (results reported here) and a 24-week secondary treatment period. Participants were recruited at 54 centres across five countries (China, Ukraine, Poland, Georgia, and Bulgaria). Patients with active rheumatoid arthritis with an inadequate response to methotrexate were randomly assigned (1:1:2) to receive reference tocilizumab up to week 48, or reference tocilizumab up to week 24 followed by BAT1806/BIIB800 up to week 48 (the two reference tocilizumab groups were analysed as a single group in this analysis), or BAT1806/BIIB800 up to week 48 (the BAT1806/BIIB800 group), administered by intravenous infusion once every 4 weeks at a starting dose of 8 mg/kg. The primary endpoint was the proportion of participants who had a 20% improvement in American College of Rheumatology criteria (ACR20) at week 12 (for the European Medicines Agency [EMA]) or week 24 (for the US Food and Drug Administration [FDA] and China National Medical Products Administration [NMPA]) using prespecified equivalence margins (95% CI -14·5 to +14·5 [EMA], 90% CI -12·0 to +15·0 [FDA], and 95% CI -13·6 to +13·6 [NMPA]). The International Council for Harmonisation E9(R1) estimand framework, with strategies for addressing intercurrent events, was implemented for the efficacy evaluations with expected differences as per the predefined equivalence margins. This trial is registered at ClinicalTrials.gov (NCT03830203) and EudraCT (2018-002202-31), and is closed to new participants. FINDINGS: Between Dec 19, 2018, and Jan 5, 2021, we randomly assigned 621 participants: 309 to the reference tocilizumab group and 312 to the BAT1806/BIIB800 group. The mean age was 50·5 years (SD 12·0), 534 (86%) were women, 87 (14%) were men, and 368 (59%) were White. For the primary estimands, estimated ACR20 response rates were 64·8% in the reference tocilizumab group and 69·0% in the BAT1806/BIIB800 group (treatment difference 4·1% [95% CI -3·6 to 11·9]) at week 12, and 67·9% in the reference tocilizumab group and 69·9% in the BAT1806/BIIB800 group (treatment difference 1·9% [90% CI -4·0 to 7·9; 95% CI -5·2 to 9·1]) at week 24. All confidence intervals were contained within the predefined equivalence margins. Comparable pharmacokinetic and immunogenicity profiles were observed for the reference tocilizumab and BAT1806/BIIB800 groups. Adverse events were reported by 201 (65%) participants in the reference tocilizumab group and 206 (66%) in the BAT1806/BIIB800 group; 196 (63%) participants in the reference tocilizumab group and 201 (64%) participants in the BAT1806/BIIB800 group reported a treatment-emergent adverse event. Five participants had a fatal event (reference tocilizumab n=1; BAT1806/BIIB800 n=4). INTERPRETATION: BAT1806/BIIB800 showed equivalent efficacy, and comparable safety, immunogenicity, and pharmacokinetic profiles as reference tocilizumab. FUNDING: Bio-Thera Solutions and Biogen.

[Effects of Photovoltaic Power Station Construction on Terrestrial Environment： Retrospect and Prospect].

With the rapid growth of global energy consumption, the environment will further deteriorate, and the competition among countries to reduce emissions will become more intense. Photovoltaic power generation using solar energy as a clean energy source is of strategic importance for achieving a carbon-neutral planet. Therein, centralized photovoltaic power stations in terrestrial ecosystems cover the earth's surface, which leads to changes in land use and has a significant effect on the surface energy balance and precipitation regimes, altering soil nutrient cycling and plant productivity, and ultimately significantly affects ecosystem functions and services. By synthesizing relevant studies on this topic over the past 20 years, we summarized the effects of photovoltaic power station construction on microclimate, soil, flora and fauna, and potential changes in terrestrial ecosystem functions. Overall, the photovoltaic power stations improved the quality of the soil condition, especially in harsh environments, and increased the vegetation coverage. In addition, photovoltaic power stations could affect ecosystem functions including plant productivity, soil erosion resistance, and soil carbon sequestration by regulating microclimatic factors such as solar radiation intensity, air temperature and humidity, wind speed, and wind direction. Although numerous studies have anticipated the potential effect of photovoltaic power stations on ecosystem structure and functions, empirical evidence remains scarce. Therefore, more studies focusing on the regional variability of the ecological impacts of photovoltaic power stations and the potential pathways of photovoltaic power stations affecting ecosystem functions are needed in the future. Improving the understanding of the ecological effects of photovoltaic power stations may help to provide a basis for ecological protection and restoration.

An Iterative Scale Purification Procedure on lz for the Detection of Aberrant Responses.

Many person-fit statistics have been proposed to detect aberrant response behaviors (e.g., cheating, guessing). Among them, lz is one of the most widely used indices. The computation of lz assumes the item and person parameters are known. In reality, they often have to be estimated from data. The better the estimation, the better lz will perform. When aberrant behaviors occur, the person and item parameter estimations are inaccurate, which in turn degrade the performance of lz. In this study, an iterative procedure was developed to attain more accurate person parameter estimates for improved performance of lz. A series of simulations were conducted to evaluate the iterative procedure under two conditions of item parameters, known and unknown, and three aberrant response styles of difficulty-sharing cheating, random-sharing cheating, and random guessing. The results demonstrated the superiority of the iterative procedure over the non-iterative one in maintaining control of Type-I error rates and improving the power of detecting aberrant responses. The proposed procedure was applied to a high-stake intelligence test.

Physiological and behavioral basis of diamondback moth Plutella xylostella migration and its association with heat stress.

BACKGROUND: Migration is a strategy that shifts insects to more favorable habitats in response to deteriorating local environmental conditions. The ecological factors that govern insect migration are poorly understood for many species. Plutella xylostella causes great losses in Brassica vegetable and oilseed crops, and undergoes mass migration. However, the physiological and behavioral basis for distinguishing migratory individuals and the factors driving its migration remain unclear. RESULTS: Daily light trap catches conducted from April to July in a field population of P. xylostella in central China revealed a sharp decline in abundance from late-May. Analysis of ovarian development levels showed that the proportion of sexually immature females gradually increased, while the mating rate decreased, indicating that generations occurring in May mainly resulted from local breeding and that emigration began in late-May. Physiological and behavioral analyses revealed that emigrant populations had a higher take-off proportion, stronger flight capacity and greater energy reserves of triglyceride compared to residents. Furthermore, a gradual increase in temperature from 24 °C to >30 °C during larval development resulted in a significant delay in oogenesis and increased take-off propensity of adults compared with the control treatment reared at a constant temperature of 24 °C. CONCLUSION: Our results provide the physiological and behavioral factors that underpin mass migration in P. xylostella, and demonstrate that exposure to increased temperature increases their migration propensity at the cost of reproductive output. This study sheds light on understanding the factors that influence population dynamics, migratory propensity and reproductive tradeoffs in migratory insects. © 2023 Society of Chemical Industry.

Niobium-Based Oxide for Anode Materials for Lithium-Ion Batteries.

Recently, it has become imperative to develop high energy density as well as high safety lithium-ion batteries (LIBS) to meet the growing energy demand. Among the anode materials used in LIBs, the currently used commercial graphite has low capacity and is a safety hazard due to the formation of lithium dendrites during the reaction. Among the transition metal oxide (TMO) anode materials, TMO based on the intercalation reaction mechanism has a more stable structure and is less prone to volume expansion than TMO based on the conversion reaction mechanism, especially the niobium-based oxide in it has attracted much attention. Niobium-based oxides have a high operating potential to inhibit the formation of lithium dendrites and lithium deposits to ensure safety, and have stable and fast lithium ion transport channels with excellent multiplicative performance. This review summarizes the recent developments of niobium-based oxides as anode materials for lithium-ion batteries, discusses the special structure and electrochemical reaction mechanism of the materials, the synthesis methods and morphology of nanostructures, deficiencies and improvement strategies, and looks into the future developments and challenges of niobium-based oxide anode materials.

Glutathione-dependent redox homeostasis is critical for chlorothalonil detoxification in tomato leaves.

Glutathione plays a critical role in plant growth, development and response to stress. It is a major cellular antioxidant and is involved in the detoxification of xenobiotics in many organisms, including plants. However, the role of glutathione-dependent redox homeostasis and associated molecular mechanisms regulating the antioxidant system and pesticide metabolism remains unclear. In this study, endogenous glutathione levels were manipulated by pharmacological treatments with glutathione synthesis inhibitors and oxidized glutathione. The application of oxidized glutathione enriched the cellular oxidation state, reduced the activity and transcript levels of antioxidant enzymes, upregulated the expression level of nitric oxide and Ca2+ related genes and the content, and increased the residue of chlorothalonil in tomato leaves. Further experiments confirmed that glutathione-induced redox homeostasis is critical for the reduction of pesticide residues. RNA sequencing analysis revealed that miRNA156 and miRNA169 that target transcription factor SQUAMOSA-Promoter Binding Proteins (SBP) and NUCLEAR FACTOR Y (NFY) potentially participate in glutathione-mediated pesticide degradation in tomato plants. Our study provides important clues for further dissection of pesticide degradation mechanisms via miRNAs in plants.

Beneficial effect and mechanism of natural resourced polysaccharides on regulating bone metabolism through intestinal flora: A review.

Bone metabolism is an important biological process for maintaining bone health. Polysaccharides of natural origin exert beneficial effects on bone metabolism. Polysaccharide molecules often have difficulty passing through the intestinal cell membrane and are directly absorbed in the gastrointestinal tract. Therefore, polysaccharides may affect intestinal flora and play a role in disease treatment. We performed a comprehensive review of the relevant literature published from 2003 to 2023. We found that several polysaccharides from traditional Chinese medicines, including Astragalus, Achyranthes bidentata and Eucommia ulmoides, and the polysaccharides from several dietary fibers mainly composed of inulin, resistant starch, and dextran could enrich the intestinal microbiota group to regulate bone metabolism. The promotion of polysaccharide decomposition by regulating the Bacteroides phylum is particularly critical. Studies on the structure-activity relationship showed that molecular weight, glycosidic bonds, and monosaccharide composition may affect the ability of polysaccharides. The mechanism by which polysaccharides regulate intestinal flora to enhance bone metabolism may be related to the regulation of short-chain fatty acids, immunity, and hormones, involving some signaling pathways, such as TGF-ß, Wnt/ß-catenin, BMP/Smads, and RANKL. This paper provides a useful reference for the study of polysaccharides and suggests their potential application in the treatment of bone metabolic disorders.

Hepatic retinaldehyde deficiency is involved in diabetes deterioration by enhancing PCK1- and G6PC-mediated gluconeogenesis.

Type 2 diabetes (T2D) is often accompanied with an induction of retinaldehyde dehydrogenase 1 (RALDH1 or ALDH1A1) expression and a consequent decrease in hepatic retinaldehyde (Rald) levels. However, the role of hepatic Rald deficiency in T2D progression remains unclear. In this study, we demonstrated that reversing T2D-mediated hepatic Rald deficiency by Rald or citral treatments, or liver-specific Raldh1 silencing substantially lowered fasting glycemia levels, inhibited hepatic glucogenesis, and downregulated phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) expression in diabetic db/db mice. Fasting glycemia and Pck1/G6pc mRNA expression levels were strongly negatively correlated with hepatic Rald levels, indicating the involvement of hepatic Rald depletion in T2D deterioration. A similar result that liver-specific Raldh1 silencing improved glucose metabolism was also observed in high-fat diet-fed mice. In primary human hepatocytes and oleic acid-treated HepG2 cells, Rald or Rald + RALDH1 silencing resulted in decreased glucose production and downregulated PCK1/G6PC mRNA and protein expression. Mechanistically, Rald downregulated direct repeat 1-mediated PCK1 and G6PC expression by antagonizing retinoid X receptor α, as confirmed by luciferase reporter assays and molecular docking. These results highlight the link between hepatic Rald deficiency, glucose dyshomeostasis, and the progression of T2D, whilst also suggesting RALDH1 as a potential therapeutic target for T2D.

Green tea polyphenols alleviate di-(2-ethylhexyl) phthalate-induced liver injury in mice.

BACKGROUND: Di (2-ethylhexyl) phthalate (DEHP) is a common plasticizer known to cause liver injury. Green tea is reported to exert therapeutic effects on heavy metal exposure-induced organ damage. However, limited studies have examined the therapeutic effects of green tea polyphenols (GTPs) on DEHP-induced liver damage. AIM: To evaluate the molecular mechanism underlying the therapeutic effects of GTPs on DEHP-induced liver damage. METHODS: C57BL/6J mice were divided into the following five groups: Control, model [DEHP (1500 mg/kg bodyweight)], treatment [DEHP (1500 mg/kg bodyweight) + GTP (70 mg/kg bodyweight), oil, and GTP (70 mg/kg bodyweight)] groups. After 8 wk, the liver function, blood lipid profile, and liver histopathology were examined. Differentially expressed micro RNAs (miRNAs) and mRNAs in the liver tissues were examined using high-throughput sequencing. Additionally, functional enrichment analysis and immune infiltration prediction were performed. The miRNA-mRNA regulatory axis was elucidated using the starBase database. Protein expression was evaluated using immunohistochemistry. RESULTS: GTPs alleviated DHEP-induced liver dysfunction, blood lipid dysregulation, fatty liver disease, liver fibrosis, and mitochondrial and endoplasmic reticulum lesions in mice. The infiltration of macrophages, mast cells, and natural killer cells varied between the model and treatment groups. mmu-miR-141-3p (a differentially expressed miRNA), Zcchc24 (a differentially expressed mRNA), and Zcchc24 (a differentially expressed protein) constituted the miRNA-mRNA-protein regulatory axis involved in mediating the therapeutic effects of GTPs on DEHP-induced liver damage in mice. CONCLUSION: This study demonstrated that GTPs mitigate DEHP-induced liver dysfunction, blood lipid dysregulation, fatty liver disease, and partial liver fibrosis, and regulate immune cell infiltration. Additionally, an important miRNA-mRNA-protein molecular regulatory axis involved in mediating the therapeutic effects of GTPs on DEHP-induced liver damage was elucidated.

[Clinical Characteristics and Survival Analysis of Carbapenem-Resistant Pseudomonas Aeruginosa Colonized or Infected Patients with Hematological Disorders].

OBJECTIVE: To observe the clinical characteristics and impact on mortality of carbapenem-resistant Pseudomonas aeruginosa (CRPA) colonized or infected patients with hematological disorders in order to provide evidence for the prevention and treatment of CRPA. METHODS: The patients who were colonized or infected with CRPA in the Department of Hematology of The First Affiliated Hospital of Zhejiang Chinese Medical University from January 2020 to March 2021 were selected as the research subjects, the clinical data such as hospitalization time, primary disease treatment regimen, granulocyte count, previous infection and antibiotic regimen of these patients were analyzed, meanwhile, antibiotic regimen and efficacy during CRPA infection, 30-day and long-term survival were also analyzed. RESULTS: A total of 59 patients were included in this study, and divided into CRPA infection group (43 cases) and CRPA colonization group (16 cases). Univariate logistic regression analysis showed that ECOG score (P =0.003), agranulocytosis (P <0.001), and exposure to upper than 3rd generations of cephalosporins and tigecycline within 30 days (P =0.035, P =0.017) were the high-risk factors for CRPA infection. Multivariate logistic regression analysis showed that ECOG score of 3/4 ( OR=10.815, 95%CI: 1.260-92.820, P =0.030) and agranulocytosis ( OR=13.82, 95%CI: 2.243-85.176, P =0.005) were independent risk factors for CRPA infection. There was a statistically significant difference in cumulative survival rate between CRPA colonization group and CRPA infection group ( χ2=14.134, P < 0.001). Kaplan-Meier survival analysis showed that the influencing factors of 30-day survival in patients with CRPA infection were agranulocytosis (P =0.022), soft tissue infection (P =0.03), and time of hospitalization before CRPA infection (P =0.041). Cox regression analysis showed that agranulocytosis was an independent risk factor affecting 30-day survival of patients with CRPA infection (HR=3.229, 95%CI :1.093-3.548, P =0.034). CONCLUSIONS: Patients with hematological disorders have high mortality and poor prognosis after CRPA infection. Bloodstream infection and soft tissue infection are the main causes of death. Patients with high suspicion of CRPA infection and high-risk should be treated as soon as possible.

Effect of permafrost degradation on carbon sequestration of alpine ecosystems.

Permafrost degradation profoundly affects carbon storage in alpine ecosystems, and the response characteristics of carbon sequestration are likely to differ at the different stages of permafrost degradation. Furthermore, the sensitivity of different stages of permafrost degradation to climate change is likely to vary. However, related research is lacking so far on the Qinghai-Tibetan Plateau (QTP). To investigate these issues, the Shule River headwaters on the northeastern margin of the QTP was selected. We applied InVEST and Noah-MP land surface models in combination with remote sensing and field survey data to reveal the dynamics of different carbon (vegetation carbon, soil organic carbon (SOC), and ecosystem carbon) pools from 2001 to 2020. A space-for-time analysis was used to explore the response characteristics of carbon sequestration along a gradient of permafrost degradation, ranging from lightly degraded permafrost (H-SP) to severely degraded permafrost (U-EUP), and to analyze the sensitivity of the permafrost degradation gradient to climate change. Our results showed that: (1) the sensitivity of mean annual ground temperature (MAGT) to climatic variables in the U-EUP was stronger than that in the H-SP and S-TP, respectively; (2) rising MAGT led to permafrost degradation, but increasing annual precipitation promoted permafrost conservation; (3) vegetation carbon, SOC, and ecosystem carbon had similar spatial distribution patterns, with their storage decreasing from the mountain area to the valley; (4) alpine ecosystems acted as carbon sinks with the rate of 0.34 Mg‧ha-1‧a-1 during 2001-2020, of which vegetation carbon and SOC accumulations accounted for 10.65 % and 89.35 %, respectively; and (5) the effects of permafrost degradation from H-SP to U-EUP on carbon density changed from promotion to inhibition.

Quantum dot heterostructures on N-doped graphene with accelerated diffusion kinetics for stable lithium-ion storage.

The high energy density and low self-discharge rate of lithium-ion batteries make them promising for large-scale energy storage. However, the practical development of such electrochemical energy storage systems relies heavily on the development of anode materials with high multiplier capacity and stable cycle life. Here, a simple and efficient one-step hydrothermal method is used to obtain stannide heterostructures, which are loaded on N-doped graphene (SnS2/SnO2@NG) that promotes Li+ diffusion for fast charge transfer. It is demonstrated that the built-in electric field generated by the electron transfer from electron-rich SnS2 to SnO2 in the stannide heterojunction collectively provides abundant cation adsorption sites, accelerating the migration of Li+ thus improving the electrochemical reaction kinetics. Besides, the SnS2/SnO2 nanoparticles have high structural stability, and the heterojunction compressive stresses obtained from density functional theory (DFT) calculations can significantly limit the structural damage. When applied as anodes in Li+ batteries with 300 cycles at 0.5 A/g, we achieved a high reversible capacity of 892.73 mAh/g. The rational design of low-cost batteries for energy storage and conversion can benefit from the quantitative design of fast and persistent charge transfer in a stannide heterostructure.