Empowering the Potassium-Sulfur Battery with Commendable Reaction Kinetics and Capacity Output by Localized High-Concentration Electrolytes.

Potassium-sulfur (K-S) batteries are one of the promising high-energy-density candidates beyond current lithium-ion batteries. Nevertheless, in practice, the utilization of K-S batteries is largely hindered due to the dissolution and shuttle effect of the cathode redox intermediates and the scarcity of an effective anode protection layer in conventional electrolytes. Herein, electrolyte engineering is applied to formulate an ether-based localized high-concentration electrolyte (LHCE) for the first time in a K-S cell with the mitigated parasitic effect of polysulfide dissolution and shuttle and the tuned anode-electrolyte interface property. A nonsolvating and polysulfide-stable fluoroether is sieved as a cosolvent in such an LHCE, which possesses the ultralow polysulfides solubility due to less roaming solvents and thus alleviates the polysulfides shuttle effect. The anion-derived solid electrolyte interphase enriched in inorganic components is constructed due to the strengthened cation-anion interplay in the primary solvation sheath and highlighted with accelerated interfacial kinetics in a K-S cell. It is validated that the proposed LHCE unlocks the theoretical capacity of the K-S cell based on the conversion between S and K2S3. It is further revealed that the lifespan is limited to the anode corrosion with severe cosolvent degradation caused by limited solvating solvent compatibility with metallic K, and the inevitable byproduct accumulation at the S cathode. The K-S cell based on the designed LHCE could achieve a prolonged lifespan with a reversible capacity of 448 mA h/gs after 80 cycles with an elaborate cathode design. This work shines a light on the electrolyte design perspective for full utilization and an in-depth mechanistic understanding of high-energy-density K-S batteries.

Progress of researches on mechanisms of acupuncture therapy in the treatment of lumbar disc herniation. / é’ˆç¸æ²»ç–—è °æ¤Žé—´ç›˜çªå‡ºç—‡ä½œç”¨æœºåˆ¶ç ”ç©¶è¿›å±•.

Lumbar intervertebral disc herniation (LDH) is a common and frequently-occurring disease, which usually causes lumbar and leg pain. Studies have shown that acupuncture can improve the symptoms of LDH patients. In the present paper, we summarize the progress of researches on the mechanisms of acupuncture underlying improvement of symptoms of LDH in recent 10 years from 1) delaying the intervertibral disc degeneration (by down-regulating the expressions of matrix metalloproteinase ï¼»MMPï¼½-3 and MMP-4, up-regulating the expressions of diosaccharides and polyglycoprotein, inhibiting apoptosis and promoting mitochondrial autophagy of nucleus pulposus cells, etc.), 2) maintaining spinal column stability (by relieving rachiasmus and improving lumbar flexor and extensor muscle strength, lowering the degree of polyfidus edema and fat infiltration, and restoring the biomechanics of the spine), 3) regulating inflammation (by inhibiting the production of proinflammatory factors and increasing the production of anti-inflammatory factors, etc.), 4) regulating immune response (by promoting the activity of T cells and other immune cells, lowering serum levels of MMP-3, transforming growth factor-ß1 and prostaglandin E2, raising serum levels of IgA, IgG and IgM to improve immune function ), 5) modulating neural structure and function (by promoting myelin regeneration of sciatic nerve fibers, and reducing the edema of Schwann cells' cytoplasm and mitochondria, and improving neural ultrastructure, and sensory and motor functions of peripheral nerves, etc.), 6) relieving lumbar pain (by down-regulating expression of Ca2+/calmodulin-dependent protein kinase and activation of lumbar spinal cord glial cells, blocking nociceptive signal conduction, regulating the levels of pain-related factors, etc.), and 7) improving local microcirculation. These results may provide scientific evidence for acupuncture treatment of LDH.

Effect of artificial natural light on the development of myopia among primary school-age children in China: a three-year longitudinal study.

AIM: To assess the efficacy of artificial natural light in preventing incident myopia in primary school-age children. METHODS: This is a prospective, randomized control, intervention study. A total of 1840 students from 39 classes in 4 primary schools in Foshan participated in this study. The whole randomization method was adopted to include classes as a group according to 1:1 randomized control. Classrooms in the control group were illuminated by usual light, and classrooms in the intervention group were illuminated by artificial natural light. All students received uncorrected visual acuity and best-corrected visual acuity measurement, non-cycloplegic autorefraction, ocular biometric examination, slit lamp and strabismus examination. Three-year follow-up, the students underwent same procedures. Myopia was defined as spherical equivalent refraction ≤ -0.50 D and uncorrected visual acuity <20/20. RESULTS: There were 894 students in the control group and 946 students in the intervention group with a mean±SD age of 7.50±0.53y. The three-year cumulative incidence rate of myopia was 26.4% (207 incident cases among 784 eligible participants at baseline) in the control group and 21.2% (164 incident cases among 774 eligible participants at baseline) in the intervention group [difference of 5.2% (95%CI, 3.7% to 10.1%); P=0.035]. There was also a significant difference in the three-year change in spherical equivalent refraction for the control group (-0.81 D) compared with the intervention group [-0.63 D; difference of 0.18 D (95%CI, 0.08 to 0.28 D); P<0.001]. Elongation of axial length was significantly different between in the control group (0.77 mm) and the intervention group [0.72 mm; difference of 0.05 mm (95%CI, 0.01 to 0.09 mm); P=0.003]. CONCLUSION: Artificial natural light in the classroom of primary schools can result in reducing incidence rate of myopia during a period of three years.

CircST6GAL1 knockdown alleviates pulmonary arterial hypertension by regulating miR-509-5p/multiple C2 and transmembrane domain containing 2 axis.

BACKGROUND: Hypertension is a main contributing factor of cardiovascular diseases; deregulated circular RNAs are involved in the pathogenesis of pulmonary arterial hypertension (PAH). Herein, we evaluated the function and mechanism of circST6GAL1 in PAH process. METHODS: Human pulmonary artery smooth muscle cells (HPASMCs) were cultured in hypoxic environment for functional analysis. The cell counting kit-8, 5-ethynyl-2'-deoxyuridine, wound healing, and flow cytometry assays were used to investigate cell proliferation, migration, and apoptosis. qRT-PCR and Western blotting analyses were used for level measurement of genes and proteins. The binding between miR-509-5p and circST6GAL1 or multiple C2 and transmembrane domain containing 2 (MCTP2) was analyzed by dual-luciferase reporter, RNA immunoprecipitation, and pull-down assays. The monocrotaline (MCT)-induced PAH mouse models were established for in vivo assay. RESULTS: CircST6GAL1 was highly expressed in PAH patients and hypoxia-induced HPASMCs. Functionally, circST6GAL1 deficiency reversed hypoxia-induced proliferation and migration, as well as apoptosis arrest in HPASMCs. Mechanistically, circST6GAL1 directly targeted miR-509-5p, and MCTP2 was a target of miR-509-5p. Rescue assays showed that the regulatory effects of circST6GAL1 deficiency on hypoxia-induced HPASMCs were abolished. Moreover, forced expression of miR-509-5p suppressed HPASMC proliferation and migration and induced cell apoptosis under hypoxia stimulation, while these effects were abolished by MCTP2 overexpression. Moreover, circST6GAL1 silencing improved MCT-induced pulmonary vascular remodeling and PAH. CONCLUSION: CircST6GAL1 deficiency reversed hypoxia-induced proliferation and migration, as well as apoptosis arrest in HPASMCs, and alleviated pulmonary vascular remodeling in MCT-induced PAH mouse models through the miR-509-5p/MCTP2 axis, indicating a potential therapeutic target for PAH.

Patient preferences for treatment attributes in moderate-to-severe atopic dermatitis: a discrete choice experiment.

Purpose: Evidence on treatment preferences of patients with moderate-to-severe atopic dermatitis (AD) in the United States (US) is limited and an assessment of treatment preferences in this group is warranted.Materials and methods: An online discrete choice experiment survey was conducted (June 2023) among US adults with self-reported moderate-to-severe AD or experience with systemic therapy who had inadequate response to topical treatments. Preference weights estimated from conditional logistic regression models were used to calculate willingness to trade off and attributes' relative importance (RI).Results: Participants (N = 300; mean age: 45 years; 70% females; 52% systemic therapy experienced) preferred treatments with higher efficacy, lower risk of adverse events (AEs), and less frequent blood tests (p < .05). Treatment attributes, from high to low RI, were itch control (38%), risk of cancer (23%), risk of respiratory infections (18%), risk of heart problems (11%), sustained improvement in skin appearance (5%), blood test frequency (3%), and frequency and mode of administration (2%); together, AE attributes accounted for more than half of the RI.Conclusions: Participants preferred AD treatments that maximize itch control while minimizing AE risks, whereas mode of administration had little impact on preferences. Understanding patients' preferences may help improve shared decision-making, potentially leading to enhanced patient satisfaction with treatment, increased engagement, and better clinical outcomes.

Risk factors and survival outcomes in children with early cardiotoxicity after allogeneic hematopoietic stem cell transplantation.

Cardiotoxicity in children is a potentially fatal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT); therefore, early identification of risk factors can improve patient prognosis. However, there are few data on the clinical characteristics of early-stage cardiotoxicity in children after allo-HSCT. We conducted a retrospective single-center study of pediatric patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between January 2016 and December 2022 at the Children's Hospital Affiliated with Chongqing Medical University to evaluate the clinical characteristics of early cardiac events (ECEs) after allo-HSCT and their impact on survival outcomes. We enrolled 444 patients who underwent allo-HSCT-304 males (68%) and 140 females (32%)-with a median age of 3.3 years (1.8-6.5 years) at transplantation. We found that 73 patients (16.4%) had ECEs after allo-HSCT. The ECEs included valvular disease (n = 46), pericardial effusion (n = 38), arrhythmia (n = 9), heart failure (n = 16), and dilated cardiomyopathy (n = 1). Female sex, age ≥ 6 years, body mass index (BMI) < 16 kg/m2 and HLA-type mismatches were risk factors for ECEs. We designed a stratified cardiac risk score that included these risk factors, and the higher the score was, the greater the cumulative incidence of ECEs. The occurrence of an ECE was closely associated with a lower overall survival (OS) rate and greater nonrelapse mortality (NRM). In addition, stratified analysis based on the number of combined ECEs showed that the greater the number of combined ECEs was, the more significant the negative impact on OS rates.

CG9920 is necessary for mitochondrial morphogenesis and individualization during spermatogenesis in Drosophila melanogaster.

Drosophila melanogaster is an ideal model organism for investigating spermatogenesis due to its powerful genetics, conserved genes and visible morphology of germ cells during sperm production. Our previous work revealed that ocnus (ocn) knockdown resulted in male sterility, and CG9920 was identified as a significantly downregulated protein in fly abdomen after ocn knockdown, suggesting a role of CG9920 in male reproduction. In this study, we found that CG9920 was highly expressed in fly testes. CG9920 knockdown in fly testes caused male infertility with no mature sperms in seminal vesicles. Immunofluorescence staining showed that depletion of CG9920 resulted in scattered spermatid nuclear bundles, fewer elongation cones that did not migrate to the anterior region of the testis, and almost no individualization complexes. Transmission electron microscopy revealed that CG9920 knockdown severely disrupted mitochondrial morphogenesis during spermatogenesis. Notably, we found that CG9920 might not directly interact with Ocn, but rather was inhibited by STAT92E, which itself was indirectly affected by Ocn. We propose a possible novel pathway essential for spermatogenesis in D. melanogaster, whereby Ocn indirectly induces CG9920 expression, potentially counteracting its inhibition by the JAK-STAT signaling pathway.

Total Synthesis of Quebrachamine and Kopsiyunnanine D.

The total syntheses of (±)-quebrachamine and (±)-kopsiyunnanine D are reported. Key transformations include an intermolecular Horner-Wadsworth-Emmons olefination to merge the two fragments convergently and an intramolecular Mitsunobu reaction to introduce the synthetically challenging nine-membered azonane ring efficiently.

Stability and Bioaccessibility of Quercetin-Enriched Pickering Emulsion Gels Stabilized by Cellulose Nanocrystals Extracted from Rice Bran.

To investigate the optimal delivery system of quercetin, in this paper, cellulose nanocrystals (CNCs) extracted from rice bran were used to stabilize the Pickering emulsion and Pickering emulsion gels (PEGs) with quercetin. To compare the emulsion properties, stability, antioxidation activity, encapsulation rate, and bioaccessibility of the quercetin, four emulsions of CNC Pickering emulsion (C), CNC Pickering emulsion with quercetin (CQ), CNC Pickering gel emulsion (CG), and CNC Pickering gel emulsions with quercetin (CQG) were prepared. All four emulsions exhibited elastic gel network structure and good stability. The quercetin significantly reduced the particle size, increased the stability, and improved the antioxidant capacity of CQ and CQG. Compared to C and CG, the ABTS+ radical scavenging capacities of CQ and CQG were respectively enhanced by 46.92% and 3.59%. In addition, CQG had a higher encapsulation rate at 94.57% and higher bioaccessibility (16.17) compared to CQ. This study not only indicated that CNC from rice bran could be exploited as an excellent stabilization particle for Pickering emulsions, but also provided a highly stable and bioaccessible delivery system for water-insoluble functional active factors.

Chromosomal integration and plasmid fusion occurring in ST20 carbapenem-resistant Klebsiella pneumoniae isolates coharboring blaNDM-1 and blaIMP-4 induce resistance transmission and fitness variation.

To investigate the epidemiology of ST20 carbapenem-resistant Klebsiella pneumoniae (CRKP) in China, and further explore the genomic characteristics of blaIMP-4 and blaNDM-1 coharboring isolates and plasmid contributions to resistance and fitness. Seven ST20 CRKP isolates were collected nationwide, and antimicrobial susceptibility testing was performed. Antimicrobial resistance genes, virulence genes, and plasmid replicons were identified via whole-genome sequencing, and clonality assessed via core-genome multilocus sequence typing. Furthermore, we found four dual-metallo-ß-lactamases (MBL)-harbouring isolates, the gene location was detected by Southern blotting, and plasmid location analysis showed that blaIMP-4 was located on a separate plasmid, a self-conjugative fusion plasmid, or the bacterial chromosome. These isolates were subjected to long-read sequencing, the presence of blaIMP-4 in different locations was identified by genomic comparison, and transposon units were detected via inverse PCR. We subsequently found that blaIMP-4 on the fusion plasmid and bacterial chromosome was formed via intact plasmid recombination by the IS26 and ltrA, respectively, and the circular transposon unit was related to cointegration, however, blaIMP-4 in different locations did not affect the gene stability. The blaNDM-1-harbouring plasmid contributed to the increased resistance to ß-lactams and shortened survival lag time which was revealed in plasmid cured isolates. In summary, the K. pneumoniae ST20 clone is a high-risk resistant clone. With the use of ceftazidime/avibactam, MBL-positive isolates, especially dual-MBL-harbouring isolates, should be given additional attention.

Endothelial dysfunction in vascular complications of diabetes: a comprehensive review of mechanisms and implications.

Diabetic vascular complications are prevalent and severe among diabetic patients, profoundly affecting both their quality of life and long-term prospects. These complications can be classified into macrovascular and microvascular complications. Under the impact of risk factors such as elevated blood glucose, blood pressure, and cholesterol lipids, the vascular endothelium undergoes endothelial dysfunction, characterized by increased inflammation and oxidative stress, decreased NO biosynthesis, endothelial-mesenchymal transition, senescence, and even cell death. These processes will ultimately lead to macrovascular and microvascular diseases, with macrovascular diseases mainly characterized by atherosclerosis (AS) and microvascular diseases mainly characterized by thickening of the basement membrane. It further indicates a primary contributor to the elevated morbidity and mortality observed in individuals with diabetes. In this review, we will delve into the intricate mechanisms that drive endothelial dysfunction during diabetes progression and its associated vascular complications. Furthermore, we will outline various pharmacotherapies targeting diabetic endothelial dysfunction in the hope of accelerating effective therapeutic drug discovery for early control of diabetes and its vascular complications.

miR-92a-3p regulates ethanol-induced apoptosis in H9c2 cardiomyocytes.

The role of miR-92a-3p in the ethanol-induced apoptosis of H9c2 cardiomyocytes remains unclear. In this study, we explored the role of miR-92a-3p in the ethanol-induced apoptosis of H9c2 cardiomyocytes and identified its target genes and signaling pathways. H9c2 cells were cultured with or without 100 mM ethanol for 24 h. The differential expression of miR-92a-3p was verified in H9c2 cells through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). To manipulate the expression of miR-92a-3p, both a mimic and an inhibitor were transfected into H9c2 cells. An Annexin V-fluorescein isothiocyanate/propidium iodide apoptosis detection kit and apoptosis-related antibodies were used for apoptosis detection through flow cytometry and Western blotting, respectively. Target genes were verified through RT-qPCR, Western blotting, and double luciferase reporter gene assays. miR-92a-3p was significantly overexpressed in ethanol-stimulated H9c2 cardiomyocytes (P < 0.001). After ethanol stimulation, H9c2 myocardial cells exhibited increased apoptosis. The apoptosis rate was higher in the miR-92a-3p mimic group than in the control group. However, the apoptosis rate was lower in the miR-92a-3p inhibitor group than in the control group, indicating that miR-92a-3p promotes the ethanol-induced apoptosis of H9c2 myocardial cells. RT-qPCR and Western blotting revealed that the miR-92a-3p mimic and inhibitor significantly regulated the mRNA and protein expression levels of mitogen- and stress-activated protein kinase 2 and cyclic AMP-responsive element-binding protein 3-like protein 2 (CREB3L2), suggesting that miR-92a-3p promotes the apoptosis of H9c2 cardiomyocytes by inhibiting the MSK2/CREB/Bcl-2 pathway. Therefore, the apoptosis of H9c2 cardiomyocytes increases after ethanol stimulation, and miR-92a-3p can directly target MSK2 and CREB3L2, thereby promoting the ethanol-induced apoptosis of H9c2 myocardial cells.

Establishment of low-cost production platforms of polyhydroxyalkanoate bioplastics from Halomonas cupida J9.

Microbial production of polyhydroxyalkanoate (PHA) is greatly restricted by high production cost arising from high-temperature sterilization and expensive carbon sources. In this study, a low-cost PHA production platform was established from Halomonas cupida J9. First, a marker-less genome-editing system was developed in H. cupida J9. Subsequently, H. cupida J9 was engineered to efficiently utilize xylose for PHA biosynthesis by introducing a new xylose metabolism module and blocking xylonate production. The engineered strain J9UΔxylD-P8xylA has the highest PHA yield (2.81 g/L) obtained by Halomonas with xylose as the sole carbon source so far. This is the first report on the production of short- and medium-chain-length (SCL-co-MCL) PHA from xylose by Halomonas. Interestingly, J9UΔxylD-P8xylA was capable of efficiently utilizing glucose and xylose as co-carbon sources for PHA production. Furthermore, fed-batch fermentation of J9UΔxylD-P8xylA coupled to a glucose/xylose co-feeding strategy reached up to 12.57 g/L PHA in a 5-L bioreactor under open and unsterile condition. Utilization of corn straw hydrolysate as the carbon source by J9UΔxylD-P8xylA reached 7.0 g/L cell dry weight (CDW) and 2.45 g/L PHA in an open fermentation. In summary, unsterile production in combination with inexpensive feedstock highlights the potential of the engineered strain for the low-cost production of PHA from lignocellulose-rich agriculture waste.

Prediction of Th17/Treg cell balance on length of stay in intensive care units of patients with sepsis.

Background: Prolonged length of stay (LOS) of sepsis can drain a hospital's material and human resources. This study investigated the correlations between T helper type 17 (Th17) and regulatory T (Treg) balance with LOS in sepsis. Methods: A prospective clinical observational study was designed in Changhai Hospital affiliated to Naval Medical University in Shanghai, China, from January to October 2020. The patients diagnosed with sepsis and who met the inclusion and exclusion criteria were recruited and whether the levels of cytokines, procalcitonin, subtypes, and biomarkers of T cells in the peripheral blood were detected. We analyzed the correlation between these and LOS. Results: Sixty septic patients were classified into two groups according to whether their intensive care unit (ICU) stay exceeded 14 days. The patients with LOS ≥14 days were older ([72.6±7.5] years vs. [63.3±10.4] years, P=0.015) and had higher Sequential Organ Failure Assessment (SOFA) (median [interquartile range]: 6.5 [5.0-11.0] vs. 4.0 [3.0-6.0], P=0.001) and higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores (16.0 [13.0-21.0] vs. 8.5 [7.0-14.0], P=0.001). There was no difference in other demographic characteristics and cytokines, interleukin-6, tumor necrosis factor-α, and interleukin-10 between the two groups. The Th17/Treg ratio of sepsis with LOS <14 days was considerably lower (0.48 [0.38-0.56] vs. 0.69 [0.51-0.98], P=0.001). For patients with LOS ≥14 days, the area under the receiver operating characteristic curve for the Th17/Treg ratio was 0.766. It improved to 0.840 and 0.850 when combined with the SOFA and APACHE II scores, respectively. Conclusions: The Th17/Treg ratio was proportional to septic severity and can be used as a potential predictor of ICU stay in sepsis, presenting a new option for ICU practitioners to better care for patients with sepsis.

Integration of network pharmacology, lipidomics, and transcriptomics analysis to reveal the mechanisms underlying the amelioration of AKT-induced nonalcoholic fatty liver disease by total flavonoids in vine tea.

Nonalcoholic fatty liver disease (NAFLD) is the main reason for chronic liver diseases and malignancies. Currently, there is a lack of approved drugs for the prevention or treatment of NAFLD. Vine tea (Ampelopsis grossedentata) has been used as a traditional Chinese beverage for centuries. Vine tea carries out several biological activities including the regulation of plasma lipids and blood glucose, hepato-protective function, and anti-tumor activity and contains the highest content of flavonoids. However, the underlying mechanisms of total flavonoids from vine tea (TF) in the attenuation of NAFLD remain unclear. Therefore, we investigated the interventions and mechanisms of TF in mice with NAFLD using an integrated analysis of network pharmacology, lipidomics, and transcriptomics. Staining and biochemical tests revealed a significant increase in AKT-overexpression-induced (abbreviated as AKT-induced) NAFLD in mice. Lipid accumulation in hepatic intracellular vacuoles was alleviated after TF treatment. In addition, TF reduced the hepatic and serum triglyceride levels in mice with AKT-induced NAFLD. Lipidomics results showed 32 differential lipids in the liver, mainly including triglycerides (TG), diglycerides (DG), phosphatidylcholine (PC), and phosphatidylethanolamine (PE). Transcriptomic analysis revealed that 314 differentially expressed genes were commonly upregulated in the AKT group and downregulated in the TF group. The differential regulation of lipids by the genes Pparg, Scd1, Chpt1, Dgkz, and Pla2g12b was further revealed by network enrichment analysis and confirmed by RT-qPCR. Furthermore, we used immunohistochemistry (IHC) to detect changes in the protein levels of the key proteins PPARγ and SCD1. In summary, TF can improve hepatic steatosis by targeting the PPAR signaling pathway, thereby reducing de novo fatty acid synthesis and modulating the glycerophospholipid metabolism.

Predicting adverse events after thoracic endovascular aortic repair for patients with type B aortic dissection.

The potential of adverse events (AEs) after thoracic endovascular aortic repair (TEVAR) in patients with type B aortic dissection (TBAD) has been reported. To avoid the occurrence of AEs, it is important to recognize high-risk population for prevention in advance. The data of 261 patients with TBAD who received TEVAR between June 2017 and June 2021 at our medical center were retrospectively reviewed. After the implementation of exclusion criteria, 172 patients were finally included, and after 2.8 years (range from 1 day to 5.8 years) of follow up, they were divided into AEs (n = 41) and non-AEs (n = 131) groups. We identified the predictors of AEs, and a prediction model was constructed to calculate the specific risk of postoperative AEs at 1, 2, and 3 years, and to stratify patients into high-risk (n = 78) and low-risk (n = 94) group. The prediction model included seven predictors: Age > 75 years, Lower extremity malperfusion (LEM), NT-proBNP > 330 pg/ml, None distal tear, the ratio between the diameter of the ascending aorta and descending aorta (A/D ratio) > 1.2, the ratio of the area of the false lumen to the total aorta (FL ratio) > 64%, and acute TEVAR, which exhibited excellent predictive accuracy performance and discriminatory ability with C statistic of 82.3% (95% CI 77.3-89.2%). The prediction model was contributed to identify high-risk patients of postoperative AEs, which may serve to achievement of personalized treatment and follow-up plans for patients.

Dexamethasone attenuates neuropathic pain through spinal microglial expression of dynorphin A via the cAMP/PKA/p38 MAPK/CREB signaling pathway.

This study aimed to elucidate the opioid mechanisms underlying dexamethasone-induced pain antihypersensitive effects in neuropathic rats. Dexamethasone (subcutaneous and intrathecal) and membrane-impermeable Dex-BSA (intrathecal) administration dose-dependently inhibited mechanical allodynia and thermal hyperalgesia in neuropathic rats. Dexamethasone and Dex-BSA treatments increased expression of dynorphin A in the spinal cords and primary cultured microglia. Dexamethasone specifically enhanced dynorphin A expression in microglia but not astrocytes or neurons. Intrathecal injection of the microglial metabolic inhibitor minocycline blocked dexamethasone-stimulated spinal dynorphin A expression; intrathecal minocycline, the glucocorticoid receptor antagonist Dex-21-mesylate, dynorphin A antiserum, and κ-opioid receptor antagonist GNTI completely blocked dexamethasone-induced mechanical antiallodynia and thermal antihyperalgesia. Additionally, dexamethasone elevated spinal intracellular cAMP levels, leading to enhanced phosphorylation of PKA, p38 MAPK and CREB. The specific adenylate cyclase inhibitor DDA, PKA inhibitor H89, p38 MAPK inhibitor SB203580 and CREB inhibitor KG-501 completely blocked dexamethasone-induced anti-neuropathic pain and increased microglial dynorphin A exprression. In conclusion, this study reveal that dexamethasone mitigateds neuropathic pain through upregulation of dynorphin A in spinal microglia, likely involving the membrane glucocorticoid receptor/cAMP/PKA/p38 MAPK/CREB signaling pathway.

HINT2 protects against pressure overload-induced cardiac remodelling through mitochondrial pathways.

Histidine triad nucleotide-binding protein 2 (HINT2) is an enzyme found in mitochondria that functions as a nucleotide hydrolase and transferase. Prior studies have demonstrated that HINT2 plays a crucial role in ischemic heart disease, but its importance in cardiac remodelling remains unknown. Therefore, the current study intends to determine the role of HINT2 in cardiac remodelling. HINT2 expression levels were found to be lower in failing hearts and hypertrophy cardiomyocytes. The mice that overexpressed HINT2 exhibited reduced myocyte hypertrophy and cardiac dysfunction in response to stress. In contrast, the deficiency of HINT2 in the heart of mice resulted in a worsening hypertrophic phenotype. Further analysis indicated that upregulated genes were predominantly associated with the oxidative phosphorylation and mitochondrial complex I pathways in HINT2-overexpressed mice after aortic banding (AB) treatment. This suggests that HINT2 increases the expression of NADH dehydrogenase (ubiquinone) flavoprotein (NDUF) genes. In cellular studies, rotenone was used to disrupt mitochondrial complex I, and the protective effect of HINT2 overexpression was nullified. Lastly, we predicted that thyroid hormone receptor beta might regulate HINT2 transcriptional activity. To conclusion, the current study showcased that HINT2 alleviates pressure overload-induced cardiac remodelling by influencing the activity and assembly of mitochondrial complex I. Thus, targeting HINT2 could be a novel therapeutic strategy for reducing cardiac remodelling.

Vine tea total flavonoids activate the AMPK/mTOR pathway to amelioration hepatic steatosis in mice fed a high-fat diet.

Vine tea (Ampelopsis grossedentata), a traditional Chinese tea, is rich in flavonoids with various biological activities. Our study found that Vine tea total flavonoids (TFs) treatment reduced the body mass and blood lipid levels and improved the hepatic tissue morphology in mice fed the high-fat diet (HFD). In vivo, TF treatment activated the hepatic adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, initiated autophagy, and regulated the expression levels of proteins for lipid metabolism in those HFD-fed mice. In vitro, TF treatment dramatically reduced the lipid droplets and triacylglycerol content in HepG2 and L02 cells treated with oleic acid (OA). These were associated with the activation of the AMPK/mTOR pathway and autophagy initiation in OA-treated hepatocytes. This phenotype was abolished in the presence of 3-methyladenine, an autophagy inhibitor. Our results indicated that the TF activation of AMPK/mTOR leads to the stimulation of autophagy and a decrease in the buildup of intracellular lipids in hepatocytes, showing the potential of TF as a therapeutic agent for nonalcoholic fatty liver disease. PRACTICAL APPLICATION: Vine tea, a tea drink, has been consumed by Chinese folk for over a thousand years. The result of this study will provide evidence that vine tea total flavonoids have potential use as a functional material for the prevention and amelioration of nonalcoholic fatty liver disease.

Risk factors for medical adhesive-related skin injury at the site of peripherally inserted central venous catheter placement in patients with cancer: a single-centre prospective study from China.

OBJECTIVES: This study aims to explore the incidence of, and risk factors for medical adhesive-related skin injury (MARSI) at peripherally inserted central venous catheter (PICC) sites in patients with cancer. DESIGN: A prospective observational cohort study was conducted at a tertiary hospital in Shenzhen, China. SETTING: This was a single-centre study conducted in a tertiary hospital in Shenzhen, China. PARTICIPANTS: A total of 340 patients with cancer and PICC placement from January 2022 to June 2023 were selected using a convenience sampling method. METHODS: Factors potentially associated with PICC-related MARSI (PICC-MARSI) were recorded, including patient demographics, and catheter placement and maintenance. Patients were divided into MARSI and non-MARSI groups. Univariate analysis was performed to screen for associated variables, and logistic regression analysis was used to identify independent risk factors for PICC-MARSI. RESULTS: Of all 340 patients enrolled, 33 (9.7%) developed PICC-MARSI, including skin tear (8, 24.2%), tension injury (5, 15.2%), irritant contact dermatitis (10, 30.3%), allergic dermatitis (7, 21.2%) and maceration (3, 9.1%). Multivariable analysis showed that age (OR=1.058, p=0.001, 95% CI 1.023-1.094), wet skin (OR=4.873, p=0.003, 95% CI 1.728-13.742), dry skin (OR=6.247, p<0.0001, 95% CI 2.239-17.431), oedema (OR=3.302, p=0.008, 95% CI 1.365-7.985), allergy history (OR=6.044, p=0.001, 95% CI 2.040-17.906), dressing type (OR=3.827, p=0.003, 95% CI 1.595-9.185), body mass index (BMI) <18.5 (OR=4.271, p=0.015, 95% CI 1.327-13.742) and BMI 25-30 (OR=2.946, p=0.027, 95% CI 1.131-7.678) were independent risk factors for PICC-MARSI. CONCLUSIONS: Proper catheter maintenance and appropriate dressing selection are crucial for the prevention of this condition.