Mesenchymal stem cells-derived exosomes alleviate liver fibrosis by targeting Hedgehog/SMO signaling.

BACKGROUND & AIMS: Despite increasing knowledge regarding the cellular and molecular mechanisms of liver fibrogenesis, there is currently no approved drug for the treatment of liver fibrosis. Mesenchymal stem cells (MSCs) are multipotent progenitor cells representing an attractive therapeutic tool for tissue damage and inflammation. This study was designed to determine the protective effect and underlying mechanism of human umbilical cord-derived MSCs (UC-MSCs) on thioacetamide-induced liver fibrosis. METHODS: Liver fibrosis was induced in mice by intraperitoneal injection of thioacetamide (TAA). Some mice were then given injection of UC-MSCs or UC-MSCs-derived exosomes (UC-MSCs-Exo) via the tail vein. Liver tissues were collected for histologic analysis. RESULTS: We found that administration of UC-MSCs significantly reduced serum alanine aminotransferase and aspartate aminotransferase levels, and attenuated hepatic inflammation and fibrosis. Moreover, the therapeutic effect of UC-MSCs-derived exosomes was similar to that of UC-MSCs. Intriguingly, UC-MSCs-Exo treatment downregulated the expression of smoothened (SMO), a fundamental component of Hedgehog signaling which plays a critical role in fibrogenesis, and subsequently inhibited the activation of hepatic stellate cells, a central driver of fibrosis in experimental and human liver injury. Furthermore, the anti-inflammatory and anti-fibrotic effects of UCMSCs- Exo was reversed by the SMO agonist SAG treatment in mice. CONCLUSION: Our findings suggest that UC-MSCs-Exo exert therapeutic effects on liver fibrosis, at least in part, through inhibiting the Hedgehog/SMO signaling pathway.

Construction of a prognostic model for ovarian cancer based on a comprehensive bioinformatics analysis of cuproptosis-associated long non-coding RNA signatures.

Ovarian cancer (OCa) is a common malignancy in women, and the role of cuproptosis and its related genes in OCa is unclear. Using the GSE14407 dataset, we analyzed the expression and correlation of cuproptosis-related genes (CRGs) between tumor and normal groups. From the TCGA-OV dataset, we identified 20 cuproptosis-related long non-coding RNAs (CuLncs) associated with patient survival through univariate Cox analysis. OCa patients were divided into early-stage and late-stage groups to analyze CuLncs expression. Cluster analysis classified patients into two clusters, with Cluster1 having a poorer prognosis. Significant differences in "Lymphatic Invasion" and "Cancer status" were observed between clusters. Seven CRGs showed significant expression differences, validated using the human protein atlas (HPA) databases. Immune analysis revealed a higher ImmuneScore in Cluster1. GSEA identified associated signaling pathways. LASSO regression included 11 CuLncs to construct and validate a survival prediction model, classifying patients into high-risk and low-risk groups. Correlations between riskScore, Cluster phenotype, ImmuneScore, and immune cell infiltration were explored. Cell experiments showed that knocking down AC023644.1 decreases OCa cell viability. In conclusion, we constructed an accurate prognostic model for OCa based on 11 CuLncs, providing a basis for prognosis assessment and potential immunotherapy targets.

Genome-wide identification of the EIN3/EIL gene family in Ginkgo biloba and functional study of a GbEIL in the ethylene signaling pathway.

ETHYLENE-INSENSITIVE3 (EIN3) or EIN3-Like (EIL) proteins, play critical roles in integrating ethylene signaling and physiological regulation in plants by modulating the expression of various downstream genes, such as ethylene-response factors (ERFs). However, little is known about the characteristics of EIN3/EILs in the gymnosperm Ginkgo biloba. In the present study, a genome-wide comparative analysis of Ginkgo EIN3/EIL gene family was performed with those from an array of species, including bryophytes (Physcomitrella patens), gymnosperms (Cycas panzhihuaensis), and angiosperms (Arabidopsis thaliana, Gossypium raimondii, Gossypium hirsutum, Oryza sativa, and Brachypodium distachyon). Within the constructed phylogenetic tree for the 53 EIN3/EILs identified, 5 GbEILs from G. biloba, 2 PpEILs from P. patens, and 3 CpEILs from C. panzhihuaensis were assigned to one cluster, suggesting that their derivation occurred after the split of their ancestors and angiosperms. Although considerable divergence accumulated in amino acid sequences along with the evolutionary process, the specific EIN3_DNA-binding domains were evolutionarily conserved among the 53 EIN3/EILs. Collinearity analysis indicated that whole-genome or segmental duplication and subsequent purifying selection might have prompted the generation and evolution of EIN3/EIL multigene families. Based on the expression patterns of five GbEILs at the four developmental stages of Ginkgo ovules, one GbEIL gene (Gb_03292) was further investigated for its role in mediating ethylene signaling. The functional activity of Gb_03292 was closely related to ethylene signaling, as it complemented the triple response via ectopic expression in ein3eil1 double mutant Arabidopsis. Additionally, GbEIL likely modulates the expression of a Ginkgo ERF (Gb_15517) by directly binding to its promoter. These results demonstrated that the GbEIL gene could have participated in mediating ethylene signal transduction during ovule development in G. biloba. The present study also provides insights into the conservation of ethylene signaling across the gymnosperm G. biloba and angiosperm species.

Tangeretin alleviates inflammation and oxidative response induced by spinal cord injury by activating the Sesn2/Keap1/Nrf2 pathway.

Spinal cord injury (SCI) is a severe disabling disease that is characterized by inflammation and oxidative reactions. Tangeretin has been shown to possess significant antioxidant and anti-inflammatory activities. The Keap1/Nrf2 pathway, downstream of the Sesn2 gene, is involved in regulating the inflammation and oxidative response. The main objective of this study was to investigate the effect of tangeretin on SCI and its possible mechanism through cell and animal models. A T9 clamp injury was used for the mouse model and the LPS-induced stimulation of BV-2 cells was used for the cell model. The improvement of motor function after SCI was assessed by open field, swimming, and footprint experiments. The morphological characteristics of mouse spinal cord tissue and the levels of INOS, Sesn2, TNF-α, Keap1, Nrf2, IL-10, and reactive oxygen species (ROS) in vivo and in vitro were measured by several methods including western blotting, qPCR, immunofluorescence, HE, and Nissl staining. In vivo data showed that tangeretin can improve motor function recovery and reduce neuron loss and injury size in mice with SCI. Simultaneously, the in vitro findings suggested that treatment of BV-2 cells with tangeretin after LPS stimulation reduced the production of inflammatory factors and ROS, and could convert BV-2 cells from the M1 to the M2 type. Furthermore, Sesn2 knockout suppressed Keap1/Nrf2, inflammatory factors, ROS levels, and the M1 to M2 transition. Tangeretin can alleviate the inflammation and oxidative response induced by SCI by activating the Sesn2/Keap1/Nrf2 pathway.

From the Public Health Perspective: a Scalable Model for Improving Epidemiological Testing Efficacy in Low- and Middle-Income Areas.

The globe is an organically linked whole, and in the pandemic era, COVID-19 has brought heavy public safety threats and economic costs to humanity as almost all countries began to pay more attention to taking steps to minimize the risk of harm to society from sudden-onset diseases. It is worth noting that in some low- and middle-income areas, where the environment for epidemic detection is complex, the causative and comorbid factors are numerous, and where public health resources are scarce. It is often more difficult than in other areas to obtain timely and effective detection and control in the event of widespread virus transmission, which, in turn, is a constant threat to local and global public health security. Pandemics are preventable through effective disease surveillance systems, with nonpharmacological interventions (NPIs) as the mainstay of the control system, effectively controlling the spread of epidemics and preventing larger outbreaks. However, current state-of-the-art NPIs are not applicable in low- and middle-income areas and tend to be decentralized and costly. Based on a 3-year case study of SARS-CoV-2 preventive detection in low-income areas in south-central China, we explored a strategic model for enhancing disease detection efficacy in low- and middle-income areas. For the first time, we propose an integrated and comprehensive approach that covers structural, social, and personal strategies to optimize the epidemic surveillance system in low- and middle-income areas. This model can improve the local epidemic detection efficiency, ensure the health care needs of more people, reduce the public health costs in low- and middle-income areas in a coordinated manner, and ensure and strengthen local public health security sustainably.

Associations of lifestyle characteristics with circulating immune markers in the general population based on NHANES 1999 to 2014.

Lifestyles maybe associated with the immune and inflammatory state of human body. We aimed to comprehensively explore the relationship between lifestyles and circulating immune-inflammatory markers in the general population. Data from NHANES 1999-2014 was used. Lifestyle factors included leisure-time physical activity (LTPA), diet quality (Healthy Eating Index-2015, HEI-2015), alcohol consumption, cigarettes smoking, sleep hour and sedentary time. Immune makers included C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR). Generalized linear regression models were used to adjust confounders. Regressions of restricted cubic splines were utilized to evaluate the potentially non-linear relationships between exposures and outcomes. As results, HEI was negatively associated with CRP (P < 0.001), SII (P < 0.001), and NLR (P < 0.001). Cigarettes per day was positively associated with CRP (P < 0.001), SII (P < 0.001), and NLR (P = 0.008). Alcohol consumption was negatively associated with CRP (P < 0.001), but positively associated with PLR (P = 0.012) and MLR (P < 0.001). Physical activity was negatively associated with CRP (P < 0.001), SII (P = 0.005), and NLR (P = 0.002), but positively associated with PLR (P = 0.010). Participants with higher healthy lifestyle score had significantly lower CRP, SII and NLR (all P values < 0.05). Most of the sensitivity analyses found similar results. In conclusion, we found significant associations between lifestyles and immune markers in the general population, which may reflect a systemic inflammatory response to unhealthy lifestyles.

DCAF2 regulates the proliferation and differentiation of mouse progenitor spermatogonia by targeting p21 and thymine DNA glycosylase.

DDB1-Cullin-4-associated factor-2 (DCAF2, also known as DTL or CDT2), a conserved substrate recognition protein of Cullin-RING E3 ligase 4 (CRL4), recognizes and degrades several substrate proteins during the S phase to maintain cell cycle progression and genome stability. Dcaf2 mainly expressed in germ cells of human and mouse. Our study found that Dcaf2 was expressed in mouse spermatogonia and spermatocyte. The depletion of Dcaf2 in germ cells by crossing Dcaf2fl/fl mice with stimulated by retinoic acid gene 8(Stra8)-Cre mice caused a reduction in progenitor spermatogonia and differentiating spermatogonia, eventually leading to the failure of meiosis initiation and male infertility. Further studies showed that depletion of Dcaf2 in germ cells caused abnormal accumulation of the substrate proteins, cyclin-dependent kinase inhibitor 1A (p21) and thymine DNA glycosylase (TDG), decreasing of cell proliferation, increasing of DNA damage and apoptosis. Overexpression of p21 or TDG attenuates proliferation and increases DNA damage and apoptosis in GC-1 cells, which is exacerbated by co-overexpression of p21 and TDG. The findings indicate that DCAF2 maintains the proliferation and differentiation of progenitor spermatogonia by targeting the substrate proteins p21 and TDG during the S phase.

Upregulation of rate-limiting enzymes in cholesterol metabolism by PKCδ mediates endothelial apoptosis in diabetic wound healing.

Diabetic foot ulcer (DFU) is a prevalent complication of diabetes that poses significant challenges in terms of treatment and management. It is characterized by heightened endothelial apoptosis and impaired angiogenesis. In this study, we aimed to investigate the role of protein kinase Cδ (PKCδ) in regulating endothelial apoptosis in diabetic wounds by promoting cholesterol biosynthesis. The expression of PKCδ was increased in human umbilical vascular endothelial cells (HUVECs) cultivated in high glucose medium and skin tissue isolated from diabetic mice. High glucose-induced HUVECs apoptosis was reduced by PKCδ inhibition with siRNA or rottlerin. RNA-seq identified two enzymes, 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), as the downstream of PKCδ. PKCδ knockdown or inhibition suppressed the expression of HMGCS1 and HMGCR and lowered free cholesterol (FC) levels. Cholesterol restored high glucose-induced apoptosis in siRNA- or rottlerin-treated HUVECs. In vivo use of rosuvastatin calcium, an inhibitor of HMGCR, downregulated free cholesterol levels and accelerated the wound healing process. In conclusion, PKCδ expression in endothelial cells was activated by high glucose, which subsequently upregulates the expression of two enzymes catalyzing cholesterol biosynthesis, HMGCS1 and HMGCR. Enhanced cholesterol biosynthesis raises free cholesterol levels, promotes endothelial apoptosis, and finally delays wound healing.

Pretreatment with Inflammatory Factors Altered the Secretome of Human Amniotic Epithelial Cells.

Human amniotic epithelial cells (hAECs) are novel and promising therapeutic agents for patients suffering from degenerative diseases. Studies have demonstrated that the therapeutic effects of hAECs mainly depend on their paracrine components. Currently, appropriate pretreatment is a widely confirmed strategy for enhancing the repair potential of stem cells; however, the effect of proinflammatory factor pretreatment on hAECs and their secretome is still unclear. In this study, we used the well-characterized proinflammatory factors tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) to stimulate hAECs and analyzed the effect of TNF-α and IFN-γ on hAECs, including gene expression profile, paracrine proteins, and microRNAs (miRNAs) in exosomes. Results showed that TNF-α and IFN-γ pretreatment improved the viability of hAECs but inhibited the proliferation of hAECs. TNF-α and IFN-γ pretreatment altered the gene expression profile of hAECs, and upregulated differentially expressed genes were predominantly enriched in biological adhesion, antioxidant activity, and response to IFN-beta. In addition, TNF-α and IFN-γ pretreatment enhanced the paracrine secretion of cytokines by hAECs. The upregulated differentially expressed proteins were mainly enriched in tissue remodeling proteins and cytokine-cytokine receptor. Notably, the expression of miRNAs in exosomes from hAECs was also changed by TNF-α and IFN-γ pretreatment. The target genes of upregulated exosomal miRNAs substantially contributed to the response to stimulus, metabolic pathways, and PI3K-Akt signaling pathway. Our findings improve our understanding of the biological characteristics of hAECs after proinflammatory factor pretreatment and provide novel insights to strengthen and optimize the therapeutic potential of hAECs and their secretome in regenerative medicine.

Resistance exercise preconditioning prevents disuse muscle atrophy by inhibiting apoptosis and protein degradation via SESN2 in C57BL/6J mice.

AIM: To compare the effects of different exercise preconditioning in the context of skeletal muscle atrophy and to investigate the potential involvement of Sestrin2 (SESN2), a stress-inducible protein that can be regulated by exercise, in exercise preconditioning on preventing disuse muscle atrophy. METHODS: Eight-week-old male C57BL/6J mice were randomly assigned to sedentary groups (SD), aerobic exercise groups (AE), resistance exercise groups (RE), and combined exercise groups (CE) with or without 7 days of immobilization. The duration of the exercise intervention was 10 weeks. The effects of different exercise preconditioning to prevent muscle atrophy were analyzed by evaluating skeletal muscle function and mass. Additionally, to investigate the potential underlying mechanism of exercise-induced protection of skeletal muscle, wild-type and SESN2--/-- mice were randomly divided into sedentary group and resistance exercise preconditioning group. C2C12 cells were treated with SESN2 adenoviruses and MK2206 (an AKT inhibitor) for 48 h to elucidate the underlined mechanism. RESULTS: RE was more effective in preserving skeletal muscle function, muscle mass and maintaining skeletal muscle protein homeostasis than AE and CE under immobilized condition. Importantly, exercise performance, muscle mass to body weight ratio, and the cross-sectional area of muscle fibers were significantly lower in SESN2-/- mice than wild-type mice after resistance exercise preconditioning. Mechanistically, the absence of SESN2 led to activation of the ubiquitin-proteasome system and induction of apoptosis. In vitro experiments showed that MK2206 treatment mitigated the regulatory effects of overexpression-SESN2 on protein hydrolysis and apoptosis. CONCLUSION: RE was more effective than AE or CE in preventing disuse muscle atrophy. SESN2 mediated the protective effects of resistance exercise preconditioning on skeletal muscle atrophy.

Ni/Mg Dual Concentration-Gradient Surface Modification to Enhance Structural Stability and Electrochemical Performance of Li-Rich Layered Oxides.

Li-rich layered oxides (LRLOs), with the advantages of high specific capacity and low cost, are considered as candidates for the next-generation cathode of lithium-ion batteries (LIBs). Unfortunately, sluggish kinetics and interfacial degradation lead to capacity loss and voltage decay of the material during cycling. To address these issues, we propose a Ni/Mg dual concentration-gradient modification strategy for LRLOs. From the center to the surface of the modified materials, the contents of Ni and Mg are gradually increased while the content of Mn is decreased. The high Ni content on the surface increases the proportion of cationic redox, elevating the operating voltage and accelerating reaction kinetics. Moreover, the doped Mg on the surface of the material acting as a stabilizing pillar suppresses the migration of transition metals, stabilizing the layered structure. Therefore, the material with the Ni/Mg dual concentration-gradients delivers a superior electrochemical performance, exhibiting a suppressed voltage decay of 2.8 mV per cycle during 200 cycles (1 C, 2-4.8 V) and an excellent rate capability of 94.84 mAh/g at 7C. This study demonstrates a synergic design to construct high-performance LRLO cathode materials for LIBs.

Association of systemic inflammatory response index with ST segment elevation myocardial infarction and degree of coronary stenosis: a cross-sectional study.

BACKGROUND: Systemic Inflammatory Response Index (SIRI), a composite inflammatory marker encompassing neutrophils, monocytes, and lymphocytes, has been recognized as a reliable marker of systemic inflammation. This article undertakes an analysis of clinical data from ST-segment Elevation Myocardial Infarction (STEMI) patients, aiming to comprehensively assess the relationship between SIRI, STEMI, and the degree of coronary stenosis. METHODS: The study involved 1809 patients diagnosed with STEMI between the years 2020 and 2023. Univariate and multivariate logistic regression analyses were conducted to evaluate the risk factors for STEMI. Receiver operating characteristic (ROC) curves were generated to determine the predictive power of SIRI and neutrophil-to-lymphocyte ratio (NLR). Spearman correlation analysis was performed to assess the correlation between SIRI, NLR, and the Gensini score (GS). RESULTS: Multivariate logistic regression analysis showed that the SIRI was the independent risk factor for STEMI (adjusted odds ratio (OR) in the highest quartile = 24.96, 95% confidence interval (CI) = 15.32-40.66, P < 0.001). In addition, there is a high correlation between SIRI and GS (ß:28.54, 95% CI: 24.63-32.46, P < 0.001). The ROC curve analysis was performed to evaluate the predictive ability of SIRI and NLR for STEMI patients. The area under the curve (AUC) for SIRI was 0.789. The AUC for NLR was 0.754. Regarding the prediction of STEMI in different gender groups, the AUC for SIRI in the male group was 0.771. The AUC for SIRI in the female group was 0.807. Spearman correlation analysis showed that SIRI exhibited a stronger correlation with GS, while NLR was lower (SIRI: r = 0.350, P < 0.001) (NLR: r = 0.313, P < 0.001). CONCLUSION: The study reveals a strong correlation between the SIRI and STEMI as well as the degree of coronary artery stenosis. In comparison to NLR, SIRI shows potential in predicting acute myocardial infarction and the severity of coronary artery stenosis. Additionally, SIRI exhibits a stronger predictive capability for female STEMI patients compared to males.

Modeling the Health Impact and Cost-Effectiveness of a Combined Schoolgirl HPV Vaccination and Cervical Cancer Screening Program in Guangdong Province, China.

Low human papillomavirus (HPV) vaccine uptake is a key barrier to cervical cancer elimination. We aimed to evaluate the health impact and cost-effectiveness of introducing different HPV vaccines into immunization programs and scaling up the screening program in Guangdong. We used a dynamic compartmental model to estimate the impact of intervention strategies during 2023-2100. We implemented the incremental cost-effectiveness ratio (ICER) in costs per averted disability-adjusted life year (DALY) as an indicator to assess the effectiveness of the intervention. We used an age-standardized incidence of 4 cases per 100,000 women as the threshold for the elimination of cervical cancer. Compared with the status quo, scaling up cervical cancer screening coverage alone would prevent 215,000 (95% CI: 205,000 to 227,000) cervical cancer cases and 49,000 (95% CI: 48,000 to 52,000) deaths during 2023-2100. If the coverage of vaccination reached 90%, domestic two-dose 2vHPV vaccination would be more cost-effective than single-dose and two-dose 9vHPV vaccination. If Guangdong introduced domestic two-dose 2vHPV vaccination at 90% coverage for schoolgirls from 2023 and increased the screening coverage, cervical cancer would be eliminated by 2049 (95% CI 2047 to 2051). Introducing two doses of domestic 2vHPV vaccination for schoolgirls and expanding cervical cancer screening is estimated to be highly cost-effective to accelerate the elimination of cervical cancer in Guangdong.

Acute caval thrombosis leading to obstructive shock in the early post insertion period of an inferior vena cava filter: a case report and literature review.

BACKGROUND: Obstructive shock is extremely rare in clinical practice and is caused by acute blood flow obstruction in the central vessels of either the systemic or pulmonary circulation. Utilizing inferior vena cava filters (IVCFs) to prevent pulmonary embolism (PE) is associated with some potential complications, such as inferior vena cava thrombosis (IVCT). Shock as a direct result of IVCT is rare. We present a case of obstructive shock secondary to extensive IVCT caused by inadequate anticoagulant therapy after the placement of an IVCF. CASE PRESENTATION: A 63-year-old male patient with a traffic accident injury presented orthopaedic trauma and lower limb deep vein thrombosis (DVT). He experienced sudden and severe abdominal pain with hypotension, tachycardia, tachypnea, oliguria and peripheral oedema 5 days after IVCF placement and 3 days after cessation of anticoagulant therapy. Considering that empirical anti-shock treatment lasted for a while and the curative effect was poor, we finally recognized the affected vessels and focused on the reason for obstructive shock through imaging findings-inferior vena cava thrombosis and occlusion. The shock state immediately resolved after thrombus aspiration. The same type of shock occurred again 6 days later during transfer from the ICU to general wards and the same treatment was administered. The patient recovered smoothly in the later stage, and the postoperative follow-up at 1, 3, and 12 months showed good results. CONCLUSION: This case alerts clinicians that it is crucial to ensure adequate anticoagulation therapy after IVCF placement, and when a patient presents with symptoms such as hypotension, tachycardia, and lower limb and scrotal oedema postoperatively, immediate consideration should be given to the possibility of obstructive shock, and prompt intervention should be based on the underlying cause.

Morphology, surface characteristics and tribological properties of whey protein/chitosan composite particles and their fat replacing effect in O/W emulsion.

Whey protein isolate (WPI) and chitosan were used to fabricate WPI/chitosan composite particles at temperatures of 75 °C (WPI/chitosan-75) and 95 °C (WPI/chitosan-95). The morphologic structure, surface properties, and the resulting tribological characteristics of the particles were investigated. The composite particles showed larger particle size than pure WPI particles (WPI-75) (~ 509 nm), with WPI/chitosan-95 the largest (932 nm). WPI/chitosan-75 showed complete core-shell structure from microstructure results. The dispersion of WPI/chitosan-75 exhibited higher surface hydrophobicity but lower viscosity compared to WPI/chitosan-95. Tribological analysis revealed that WPI/chitosan composite particles showed dramatically lower friction coefficient (µ) than pure WPI particles at sliding speed <10 mm/s and WPI/chitosan-75 demonstrated superior lubrication effects. With the presence of artificial saliva, the µ of WPI-75 was greatly lowered at sliding speed <16 mm/s, while the values of WPI/chitosan-75 only showed a slight decrease at sliding speed <1 mm/s. Chitosan might have played the similar role as artificial saliva in lubricating on the hydrophobic surface. Moreover, the incorporation of 0.5 % WPI/chitosan-75 in the low-fat (5 %) oil-in-water emulsion led to even lower µ than full-fat (20 %) emulsion at sliding speed <10 mm/s. Hence, WPI/chitosan-75 exhibited promising potential as a fat replacement and biolubricant.

Regulating Grind-Induced Lattice Distortion for Nickel-Rich Cathodes by Annealing.

The commercialization of high-performance nickel-rich cathodes always awaits a cost-effective, environmentally friendly, and large-scale preparation method. Despite a grinding process normally adopted in the synthesis of the nickel-rich cathodes, lattice distortion, rough surface, and sharp edge transformation inevitably occurr in the resultant samples. In this work, an additional annealing process is proposed that aims at regulating lattice distortion as well as achieving round and smoother morphologies without any structural or elemental modifications. Such a structural enhancement is favored for improved lithium diffusion and electrochemical stability during cycling. Consequently, the annealed cathodes demonstrate a considerable enhancement in capacity retention, escalating from 68.7% to 91.9% after 100 cycles at 1 C. Additionally, the specific capacity is significantly increased from 64 to 142 mAh g-1 at 5 C when compared to the unannealed cathodes. This work offers a straightforward and effective approach for reinforcing the electrochemical properties of nickel-rich cathodes.

TNF-α and IFN-γ prestimulation enhances the therapeutic efficacy of human amniotic epithelial stem cells in chemotherapy-induced ovarian dysfunction.

BACKGROUND: Exposure to a harsh ovarian microenvironment induced by chemotherapeutic agents seriously affects the remodeling of ovarian function and follicular development, leading to premature ovarian failure or insufficiency (POF/POI). For decades, the effectiveness of stem cell therapies in POI animal models has been intensively studied; however, strategies to enhance the therapeutic effect of stem cells remain challenging. METHODS: In this study, we first observed the pathological changes of the ovaries at different time points during chemotherapy, including the number of follicles, granulosa cell proliferation, oxidative stress damage, ovarian fibrosis, and inflammatory reaction. Moreover, we investigated whether activated hAECs stimulated by the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were more effective than native hAECs in repairing ovarian injury induced by chemotherapy. RESULTS: The inhibitory effect of chemotherapy drugs on ovarian granulosa cells (GCs) in growing follicles mainly occurred on day 3 after chemotherapy in a mouse model. Then, continued ovarian injury, including oxidative damage and cell death cascades, resulted in the depletion of follicular reserves and inflammation-related ovarian fibrosis. Cytokine array demonstrated that activated hAECs secreted high levels of paracrine cytokines related to extracellular matrix (ECM) remodeling, angiogenesis, and immunomodulation. An in vivo study showed that the engraftment rate of activated hAECs in damaged ovaries was higher than that of native hAECs. Furthermore, activated hAECs in damaged ovaries had significantly upregulated expression of the antioxidant proteins thioredoxin1/2. In addition, activated hAECs had increased numbers of mature follicles and ameliorated the ovarian microenvironment by promoting angiogenesis and reducing ovarian fibrosis. CONCLUSIONS: These results indicated that secondary ovarian damage induced by chemotherapy, including oxidative stress damage, chronic inflammatory response, and ovarian tissue fibrosis should be attended. Prestimulation with the proinflammatory factors TNF-α and IFN-γ could enhance the therapeutic efficacy of hAECs against chemotherapy-induced ovarian dysfunction, which may become a new feasible strategy to improve the therapeutic potential of hAECs in regenerative medicine.

Construction of risk prediction model for hyponatremia in patients with acute decompensated heart failure.

BACKGROUND: Patients with Heart failure (HF) commonly have a water-electrolyte imbalance due to various reasons and mechanisms, and hyponatremia is one of the most common types. However, currently, there are very few local studies on hyponatremia risk assessment in patients with acute decompensated heart failure (ADHF), and there is a lack of specific screening tools. The aim of this study is to identify a prediction model of hyponatremia in patients with acute decompensated heart failure (ADHF) and verify the prediction effect of the model. METHODS: A total of 532 patients with ADHF were enrolled from March 2014 to December 2019. Univariate and multivariate logistic regression analyses were performed to investigate the independently associated risk factors of hyponatremia in patients with ADHF. The prediction model of hyponatremia in patients with ADHF was constructed by R software, and validation of the model was performed using the area under the receiver operating characteristic curve (AUC) and calibration curves. RESULTS: A total of 65 patients (12.2%) had hyponatremia in patients with ADHF. Multivariate logistic regression analysis demonstrated that NYHA cardiac function classification (NYHA III vs II, OR = 12.31, NYHA IV vs II, OR = 11.55), systolic blood pressure (OR = 0.978), serum urea nitrogen (OR = 1.046) and creatinine (OR = 1.006) were five independent prognostic factors for hyponatremia in patients with ADHF. The AUC was 0.757; The calibration curve was near the ideal curve, which showed that the model can accurately predict the occurrence of hyponatremia in patients with ADHF. CONCLUSIONS: The prediction model constructed in our study has good discrimination and accuracy and can be used to predict the occurrence of hyponatremia in patients with ADHF.

Expedited transport versus continued on-scene resuscitation for refractory out-of-hospital cardiac arrest: A systematic review and meta-analysis.

Background: The benefit of rapid transport from the scene to definitive in-hospital care versus extended on-scene resuscitation in out-of-Hospital Cardiac Arrest (OHCA) is uncertain. Aim: To assess the use of expedited transport from the scene of OHCA compared with more extended on-scene resuscitation of out-of-hospital cardiac arrest in adults. Methods: A systematic search of the literature was conducted using MEDLINE, Embase, and SCOPUS. Randomised control trials (RCTs) and observational studies were included. Studies reporting transport timing for OHCA patients with outcome data on survival were identified and reviewed. Two investigators assessed studies identified by screening for relevance and assessed bias using the ROBINS-I tool. Studies with non-dichotomous timing data or an absence of comparator group(s) were excluded. Outcomes of interest included survival and favourable neurological outcome. Survival to discharge and favourable neurological outcome were meta-analysed using a random-effects model. Results: Nine studies (eight cohort studies, one RCT) met eligibility criteria and were considered suitable for meta-analysis. On pooled analysis, expedited (or earlier) transfer was not predictive of survival to discharge (odds ratio [OR] 1.16, 95% confidence interval [CI] 0.53 to 2.53, I2 = 99%, p = 0. 65) or favorable neurological outcome (OR 1.06, 95% CI 0.48 to 2.37, I2 = 99%, p = 0.85). The certainty of evidence across studies was assessed as very low with a moderate risk of bias. Region of publication was noted to be a major contributor to the significant heterogeneity observed amongst included studies. Conclusions: There is inconclusive evidence to support or refute the use of expedited transport of refractory OHCA.

Comparison of the Predicting Value of Neutrophil to high-Density Lipoprotein Cholesterol Ratio and Monocyte to high-Density Lipoprotein Cholesterol Ratio for in-Hospital Prognosis and Severe Coronary Artery Stenosis in Patients with ST-Segment Elevation Acute Myocardial Infarction Following Percutaneous Coronary Intervention: A Retrospective Study.

Background: Neutrophil to high-density lipoprotein cholesterol ratio (NHR) has demonstrated predictive value for coronary artery disease (CAD). However, few research has been conducted on the predictive capacity of NHR for Major Adverse Cardiovascular Events (MACE) following Percutaneous Coronary Intervention (PCI) or the degree of coronary artery stenosis in hospitalized ST-segment elevation myocardial infarction (STEMI) patients. Methods: The study involved 486 patients diagnosed with STEMI between the years 2020 and 2023. Univariate and multivariate logistic regression analyses were conducted to evaluate the risk factors for MACE after PCI and severe coronary artery stenosis during hospitalization. Receiver operating characteristic (ROC) curves were generated to determine predictive power of NHR and MHR. Spearman correlation analysis was performed to assess the correlation between NHR, MHR and the Gensini score (GS). Results: Multivariate logistic regression analysis showed that the NHR and MHR were the independent risk factor for MACE during hospitalization in STEMI patients (MHR: the odds ratio (OR)=2.347, 95% confidence interval (CI)=1.082-5.089, P=0.031) (NHR: OR=1.092, 95% CI=1.025-1.165, P=0.004). In addition, NHR was also an independent risk factor for high GS (NHR: OR=1.103, 95% CI=1.047-1.162, P<0.001), and the MHR was not an independent risk factor. The ROC curve analysis was performed to evaluate the predictive ability of NHR and MHR for in-hospital MACE in STEMI patients after primary PCI. The area under the curve (AUC) for NHR was 0.681. The AUC for MHR was 0.672. Regarding the prediction of high GS, the AUC for NHR was 0.649. The AUC for MHR was 0.587. Spearman correlation analysis showed that NHR exhibited stronger correlation with GS, while MHR was lower (NHR: r=0.291, P<0.001) (MHR: r=0.156, P<0.001). Conclusion: These findings highlight the potential clinical utility of NHR as a predictive indicator in STEMI patients after PCI during hospitalization, both for MACE events and the degree of coronary artery stenosis.