Role of the hydrocarbon molecular structure in CNT growth on Fe-Al catalysts.

Upgrading plastic wastes into high-value products via the thermochemical process is one of the most attractive topics. Although carbon nanotubes (CNTs) have been successfully synthesized from plastic pyrolysis gas over Fe-, Co-, or Ni-based catalysts, a deep discussion about the reaction mechanism was seldom mentioned in the literature. Herein, this work was intended to study the growth mechanism of CNTs from hydrocarbons on Fe-Al2O3 catalysts. C5-C7 hydrocarbons were used to synthesize CNTs in a high-temperature fixed-bed reactor, and the carbon products and cracked gas were analyzed in detail. The CNT yield was in the order of cyclohexane, cyclohexene > n-hexane > n-heptane > n-pentane, 1-hexene. It was proposed that CNT growth on Fe-Al2O3 catalysts was mainly determined by the yield and structure of six-membered cyclic species, which was tailored by the carbon chain length, C-C/CC bonds, and linear/cyclic structures of C5-C7 hydrocarbons. Compared with n-hexane, the six-membered rings of cyclohexane and cyclohexene promoted six-membered cyclic species formation, increasing CNT and benzene yields; the seven-membered carbon chain of n-heptane promoted methyl-six-membered cyclic species formation, decreasing CNT and benzene yields while increasing the toluene yield; the five-membered carbon chain of n-pentane and the CC bond of 1-hexene inhibited six-membered cyclic species formation, decreasing CNT and benzene yields. This work revealed the structure-activity relationship between C5-C7 hydrocarbons and CNT growth, which may direct the process design and optimization of CNT synthesis from plastic pyrolysis gas.

iTRAQ proteomics analysis of placental tissue with gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus is an endocrine and metabolic disorder that appears for the first time during pregnancy and causes varying degrees of short- and/or long-term effects on the mother and child. The etiology of the disease is currently unknown and isobaric tags for relative and absolute quantitation proteomics approach, the present study attempted to identify potential proteins in placental tissues that may be involved in the pathogenesis of GDM and adverse foetal pregnancy outcomes. METHODS: Pregnant women with GDM hospitalised were selected as the experimental group, and pregnant women with normal glucose metabolism as the control group. The iTRAQ protein quantification technology was used to screen the differentially expressed proteins between the GDM group and the normal control group, and the differentially expressed proteins were analysed by GO, KEGG, PPI, etc., and the key proteins were subsequently verified by western blot. RESULTS: Based on the proteomics of iTRAQ, we experimented with three different samples of placental tissues from GDM and normal pregnant women, and the total number of identified proteins were 5906, 5959, and 6017, respectively, which were similar in the three different samples, indicating that the results were reliable. Through the Wayne diagram, we found that the total number of proteins coexisting in the three groups was 4475, and 91 differential proteins that could meet the quantification criteria were strictly screened, of which 32 proteins were up-regulated and 59 proteins were down-regulated. By GO enrichment analysis, these differential proteins are widely distributed in extracellular membrane-bounded organelle, mainly in extracellular exosome, followed by intracellular vesicle, extracellular organelle. It not only undertakes protein binding, protein complex binding, macromolecular complex binding, but also involves molecular biological functions such as neutrophil degranulation, multicellular organismal process, developmental process, cellular component organization, secretion, regulated exocytosis. Through the analysis of the KEGG signaling pathway, it is found that these differential proteins are mainly involved in HIF-1 signaling pathway, Glycolysis/Gluconeogenesis, Central carbon metabolism in cancer, AMPK signaling pathway, Proteoglycans in cancer, Protein processing in endoplasmic reticulum, Thyroid cancer, Alcoholism, Glucagon signaling pathway. DISCUSSION: This preliminary study helps us to understand the changes in the placental proteome of GDM patients, and provides new insights into the pathophysiology of GDM.

FTO mediates bisphenol F-induced blood-testis barrier impairment through regulating ferroptosis via YTHDF1/TfRc and YTHDF2/SLC7A11 signal axis.

Bisphenol F (BPF) has been extensively utilized in daily life, which brings new hazards to male reproductive health. However, the specific functional mechanism is still unclear. Both cell and animal models were utilized for exploring the role of RNA methylation and ferroptosis and its underlying mechanisms in male reproductive injury induced by BPF. In animal model, BPF severely destroyed the integrity of the blood-testis barrier (BTB) and induced ferroptosis. Furthermore, BPF significantly affected the barrier function of TM4 cells and promoted ferroptosis. Importantly, ChIP assays revealed that BPF inhibited AR transcriptional regulation of FTO and FTO expression was downregulated in TM4 cells. Overexpression of FTO prevented the impairment of BTB by inhibiting ferroptosis in TM4 cells. Mechanistically, FTO could significantly down-regulate the m6A modification level of TfRc and SLC7A11 mRNA through MeRIP experiment. RIP experiments showed that YTHDF1 can bind to TfRc mRNA and promote its translation while YTHDF2 could bind to SLC7A11 mRNA and reduce its mRNA stability. Therefore, our results suggest that FTO plays a key role in BPF induced male reproductive toxicity through YTHDF1-TfRc axis and YTHDF2-SLC7A11 axis and may provide new ideas and methods for the prevention and treatment of male reproductive diseases associated with environmental pollutants.

A diffusion MRI tractography atlas for concurrent white matter mapping across Eastern and Western populations.

The study of brain differences across Eastern and Western populations provides vital insights for understanding potential cultural and genetic influences on cognition and mental health. Diffusion MRI (dMRI) tractography is an important tool in assessing white matter (WM) connectivity and brain tissue microstructure across different populations. However, a comprehensive investigation into WM fiber tracts between Eastern and Western populations is challenged due to the lack of a cross-population WM atlas and the large site-specific variability of dMRI data. This study presents a dMRI tractography atlas, namely the East-West WM Atlas, for concurrent WM mapping between Eastern and Western populations and creates a large, harmonized dMRI dataset (n=306) based on the Human Connectome Project and the Chinese Human Connectome Project. The curated WM atlas, as well as subject-specific data including the harmonized dMRI data, the whole brain tractography data, and parcellated WM fiber tracts and their diffusion measures, are publicly released. This resource is a valuable addition to facilitating the exploration of brain commonalities and differences across diverse cultural backgrounds.

A Mechanistic Insight into the Acidic-stable MnSb2O6 for Electrocatalytic Water Oxidation.

The abundant, active, and acidic-stable catalysts for the oxygen evolution reaction (OER) are rare to the proton exchange membrane-based water electrolysis. Mn-based materials show promise as electrocatalysts for OER in acid electrolytes. However, the relationship between the stability, activity and structure of Mn-based catalysts in acidic environments remains unclear. In this study, phase-pure MnSb2O6 was successfully prepared and investigated as a catalyst for OER in a sulfuric acid solution (pH of 2.0). A comprehensive mechanistic comparison between MnSb2O6 and Mn3O4 revealed that the rate-determining step for OER on MnSb2O6 is the direct formation of MnIV=O from MnII-H2O by the 2H+/2e- process. This process avoids the rearrangement of adjacent MnIII intermediates, leading to outstanding stability and activity.

Suicidal ideation and suicide attempts among students aged 12 to 24 after the lifting of COVID-19 restrictions in China: prevalence and associated factors.

Objective: To investigate the prevalence and associated factors of suicidal ideation and suicide attempts among adolescent and young adults in China from December 14, 2022 to February 28, 2023, when COVID-19 restrictions were lifted. Methods: Students in middle and high schools and colleges and universities in the province of Sichuan, China were asked to complete on-line cross-sectional surveys. Information was collected about sociodemographics, experiences related to the COVID-19 pandemic, suicidal ideation and suicide attempts. Participants also filled out the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 and the Social Support Rate Scale surveys. Factors associated with suicidal ideation or suicide attempts were explored using logistic regression. Results: Of the 82,873 respondents (aged 12 to 24 years), 21,292 (25.7%) reported having thought of suicide at least once in their lifetime, 10,382 (12.5%) reported having thought about suicide within the previous 12 months, and 1,123 (1.4%) reported having attempted it within the previous 12 months. Risk of lifetime suicidal ideation was higher among middle school students than among older students. Risk of suicidal ideation and risk of suicide attempts correlated directly with severity of symptoms of depression and anxiety, and inversely with level of social support. Greater risk of suicidal ideation and suicidal attempts was associated with: being female, living in an urban environment, attending a boarding school, currently being in love, having parents who divorced or remarried, having parents who exhibit non-authoritative parenting behavior, having higher family income, having been COVID-19 infected, having been quarantined for a long time, and being dissatisfied with one's education. Conclusions: Suicidal ideation and suicide attempts remain prevalent among young people in China. The potential associated factors identified in our study may be useful for targeting appropriate psychosocial interventions and developing mental health policies.

Intranasal adenovirus-vectored Omicron vaccine induced nasal immunoglobulin A has superior neutralizing potency than serum antibodies.

The upper respiratory tract is the initial site of SARS-CoV-2 infection. Nasal spike-specific secretory immunoglobulin A (sIgA) correlates with protection against Omicron breakthrough infection. We report that intranasal vaccination using human adenovirus serotype 5 (Ad5) vectored Omicron spike in people who previously vaccinated with ancestral vaccine could induce robust neutralizing sIgA in the nasal passage. Nasal sIgA was predominantly present in dimeric and multimeric forms and accounted for nearly 40% of total proteins in nasal mucosal lining fluids (NMLFs). A low-level IgG could also be detected in NMLFs but not IgM, IgD, and IgE. After a complete nasal wash, sIgA in the nasal passage could be replenished rapidly within a few hours. A comparison of purified paired serum IgA, serum IgG, and nasal sIgA from the same individuals showed that sIgA was up to 3-logs more potent than serum antibodies in binding to spikes and in neutralizing Omicron subvariants. Serum IgG and IgA failed to neutralize XBB and BA.2.86, while nasal sIgA retained potent neutralization against these newly emerged variants. Further analysis showed that sIgA was more effective than IgG or IgA in blocking spike-mediated cell-to-cell transmission and protecting hACE2 mice from XBB challenge. Using a sIgA monoclonal antibody as a reference, we estimated that the total nasal sIgA contains about 2.6-3.9% spike-specific sIgA in NMLFs collected approximately one month after intranasal vaccination. Our study provided insights for developing intranasal vaccines that can induce sIgA to build an effective and mutation-resistant first-line immune barrier against constantly emerging variants.

Comparative immunogenicity of monovalent and bivalent adenovirus vaccines carrying spikes of early and late SARS-CoV-2 variants.

AbstractThe continuous emergence of highly immune-evasive SARS-CoV-2 variants has challenged vaccine efficacy. A vaccine that can provide broad protection is desirable. We evaluated the immunogenicity of a series of monovalent and bivalent adenovirus-vectored vaccines containing the spikes of Wildtype (WT), Beta, Delta, Omicron subvariants BA.1, BA.2, BA.2.12.1, BA.2.13, BA.3, BA.5, BQ.1.1, and XBB. Vaccination in mice using monovalent vaccines elicited the highest neutralizing titers against each self-matched strain, but against other variants were reduced 2- to 73-fold. A bivalent vaccine consisting of WT and BA.5 broadened the neutralizing breadth against pre-Omicron and Omicron subvariants except XBB. Among bivalent vaccines based on the strains before the emergence of XBB, a bivalent vaccine consisting of BA.2 and BA.5 elicited the most potent neutralizing antibodies against Omicron subvariants, including XBB. In mice primed with injected WT vaccine, intranasal booster with a bivalent vaccine containing XBB and BA.5 could elicit broad serum and respiratory mucosal neutralizing antibodies against all late Omicron subvariants, including XBB. In mice that had been sequentially vaccinated with WT and BA.5, intranasal booster with a monovalent XBB vaccine elicited greater serum and mucosal XBB neutralizing antibodies than bivalent vaccines containing XBB. Both monovalent and bivalent XBB vaccines induced neutralizing antibodies against EG.5. Unlike the antibody response, which is highly variant-specific, mice receiving either monovalent or bivalent vaccines elicited comparable T-cell responses against all variants. Furthermore, intranasal but not intramuscular booster-induced antigen-specific lung resident T cells. This study provides insights into the design of the COVID-19 vaccine and vaccination strategies.

Response Mechanism of Extracellular Polymeric Substances Synthesized by Alternaria sp. on Drought Stress in Alfalfa (Medicago sativa L.).

This study investigates how extracellular polymeric substances (EPS) synthesized by dark septate endophytic (DSE) improve alfalfa's drought resistance. Drought stress was simulated in hydroponic culture, and roots were treated with different EPS concentrations to determine their effects on drought tolerance and applicable concentrations. Hydroponic solutions with 0.25 and 0.50% EPS concentrations alleviated leaf wilting and increased total plant fresh weight by 35.8 and 57.7%, respectively. SEM shows that EPS attached to the roots and may have served to protect the root system. EPS treatment significantly depressed the MDA contents of the roots, stems, and leaves. Roots responded to drought stress by increasing soluble sugar contents and antioxidant enzyme activities, while mitigating stem and leaf stress by synthesizing lipid compounds, amino acids, and organic acid metabolites. Five metabolites in the stem have been reported to be associated with plant stress tolerance and growth, namely 3-O-methyl 5-O-(2-methyl propyl) (4S)-2,6-dimethyl-4-(2-nitrophenyl)-3,4-dihydropyridine-3,5-dicarboxylate, malic acid, PA (20:1(11Z)/15:0), N-methyl-4,6,7-trihydroxy-1,2,3,4-tetrahydroisoquinoline, and 2-(S-glutathionyl) acetyl glutathione. In summary, EPS treatment induced oxidative stress and altered plant metabolism, and this in turn increased plant antioxidant capacity. The results provide a theoretical basis for the application of EPS in commercial products that increase plant resistance and ecological restoration.

Fabrication of Fe-Zr, Co-Zr, and Ni-Zr Catalysts to Boost CNTs Synthesis from Plastic Wastes and the Electrocatalytic Oxygen Evolution Reaction.

The efficient conversion of plastic wastes to high-value carbon materials like carbon nanotubes (CNTs) is one important issue about the rational recycling, reduction, and reuse of solid wastes. Herein, Fe-, Co-, and Ni-Zr catalysts were prepared and used for CNTs synthesis from polyethylene (PE) waste via a two-stage reaction system. At the same time, the effects of the PE/catalyst ratio and reaction temperature on CNTs synthesis have been studied. Compared with Co-Zr and Ni-Zr, Fe-Zr exhibited the best activity in CNTs synthesis from PE, and it achieved the highest CNTs yield of 806.3 mg/g (per gram of Fe-Zr) at 800 °C with a PE/catalyst ratio of 4. Furthermore, the obtained Fe-Zr/CNTs composite exhibited a low overpotential of 267 mV for the electrocatalytic oxygen evolution reaction (OER) at 20 mA/cm2 in 1 M KOH electrolyte solution, which was 21 mV lower than commercial RuO2 (288 mV) and 50 mV lower than Fe-Zr (317 mV). It was deduced that the in situ growth of CNTs reduced the charge transfer resistance and improved the electron transport efficiency of the Fe-Zr/CNTs composite, leading to superior activity in the electrocatalytic OER. This work provided detailed information for the preparation of the metal/CNTs composite from plastic wastes, which contributed positively to alleviate the environment and energy crisis.

IL-17 signaling pathway: A potential therapeutic target for reducing skeletal muscle inflammation.

BACKGROUND: The interleukin-17 (IL-17) signaling pathway is intricately linked with immunity and inflammation; however, the association between the IL-17 signaling pathway and skeletal muscle inflammation remains poorly understood. The study aims to investigate the role of the IL-17 signaling pathway in skeletal muscle inflammation and to evaluate the therapeutic potential of anti-IL-17 antibodies in reducing muscle inflammation. METHODS: A skeletal muscle inflammation model was induced by cardiotoxin (CTX) injection in C57BL6/J mice. Following treatment with an anti-IL-17 antibody, we conducted a comprehensive analysis integrating single-cell RNA sequencing (scRNA-seq), bioinformatics, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and Western blot techniques to elucidate underlying mechanisms. RESULTS: scRNA-seq analysis revealed a significant increase in neutrophil numbers and activity in inflamed skeletal muscle compared to other cell types, including macrophages, T cells, B cells, endothelial cells, fast muscle cells, fibroblasts, and skeletal muscle satellite cells. The top 30 differentially expressed genes within neutrophils, along with 55 chemokines, were predominantly enriched in the IL-17 signaling pathway. Moreover, the IL-17 signaling pathway exhibited heightened expression in inflamed skeletal muscle, particularly within neutrophils. Treatment with anti-IL-17 antibody resulted in the suppression of IL-17 signaling pathway expression, accompanied by reduced levels of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α, as well as decreased numbers and activity of Ly6g+/Mpo+ neutrophils compared to CTX-induced skeletal muscle inflammation. CONCLUSION: Our findings suggest that the IL-17 signaling pathway plays a crucial role in promoting inflammation within skeletal muscle. Targeting this pathway may hold promise as a therapeutic strategy for ameliorating the inflammatory micro-environment and reducing cytokine production.

Varying association of nutrient intakes with quality of life in patients receiving different modes of dialysis.

Background: Nutrients are crucial for dialysis patients, especially elderly patients. Nutrition-related complications in dialysis patients are often closely related to cardiovascular aging. However, we know little about the effect of different nutrients on the commonly used outcome predictor, health-related quality of life (HRQOL). Therefore, this study investigated the associations between different nutrients and HRQOL among dialysis patients. Methods: A cross-sectional study was conducted on 123 dialysis adults at multiple dialysis centers. The Short Form-36 Health Survey (SF-36) assesses HRQOL. Modified quantitative subjective global assessment (MQSGA) evaluates nutritional status. A 3-day dietary record evaluated nutrient intakes. Results: Among the 123 participants, 79 received hemodialysis (HD), and 44 were on peritoneal dialysis (PD). Patients with PD had a higher SF-36 score than HD (525 ± 136 vs. 375 ± 179, P < 0.001). A negative association between nutrition status and HRQOL was observed in HD (regression coefficient ß = -17.4, P < 0.001) but not in PD (ß = -12.3, P = 0.07). For HD patients, the nutrition status was negatively correlated with intakes of carbohydrates, fiber, selenium, copper, and Manganese (ß = -0.02, P = 0.032; ß = -0.3, P = 0.031; ß = -0.1, P = 0.006; ß = -2.3, P = 0.025; ß = -1.3, P = 0.003, respectively). Their HRQOL was positively associated with calories, fat, niacin, and vitamin E (ß = 2.19, P = 0.035; ß = 2.4, P = 0.043; ß = 8.5, P = 0.044; ß = 6.9, P = 0.017, respectively). Conversely, for patients with PD, only vitamin B2 was found to be adversely correlated with their nutritional status (ß = -5.2, P = 0.037), and increased intakes of vitamin A, vitamin C and fiber (ß = 0.1, P = 0.031; ß = 0.8, P = 0.028; ß = 15.8, P = 0.045, respectively) were associated with a better HRQOL. Conclusions: The nutritional intake of PD patients and HD patients affects their quality of life differently. Macronutrients significantly impact HRQOL in HD patients, while vitamins have a more substantial impact on PD patients.

Effect of heat stress on blood biochemistry and energy metabolite of the Dazu black goats.

The objective of this study was to determine the effects of heat stress (HS) on physiological, blood biochemical, and energy metabolism in Dazu black goats. Six wether adult Dazu black goats were subjected to 3 experimental periods: high HS (group H, temperature-humidity index [THI] > 88) for 15 d, moderate HS (group M, THI was 79-88) for 15 d, and no HS (group L, THI < 72) for 15 d. Rectal temperature (RT) and respiratory rate (RR) were determined on d 7 and 15 of each period, and blood samples were collected on d 15 of each period. All goats received glucose (GLU) tolerance test (GTT) and insulin (INS) tolerance test on d 7 and d 10 of each period. The results showed that HS decreased dry matter intake (DMI) and INS concentration (p < 0.05), and increased RT, RR, non-esterified fatty acid (NEFA), cortisol (COR), and total protein (TP) concentrations (p < 0.05). Compared to group L, the urea nitrogen (BUN) concentration increased and GLU concentration decreased in group H (p < 0.05). During the GTT, the area under the curve (AUC) of GLU concentrations increased by 12.26% (p > 0.05) and 40.78% (p < 0.05), and AUC of INS concentrations decreased by 26.04 and 14.41% (p < 0.05) in groups H and M compared to group L, respectively. The INS concentrations were not significant among the three groups (p > 0.05) during the ITT. A total of 60 differentially expressed metabolites were identified in response to groups H and M. In HS, changes in metabolites related to carbohydrate metabolism and glycolysis were identified (p < 0.05). The metabolites related to fatty acid ß-oxidation accumulated, glycogenic and ketogenic amino acids were significantly increased, while glycerophospholipid metabolites were decreased in HS (p < 0.05). HS significantly increased 1-methylhistidine, creatinine, betaine, taurine, taurolithocholic acid, inosine, and hypoxanthine, while decreasing vitamin E in blood metabolites (p < 0.05). In summary, HS changed the metabolism of fat, protein, and energy, impaired GLU tolerance, and mainly increased amino acid metabolism to provide energy in Dazu black goats.

The Olfactory Receptor Olfr25 Mediates Sperm Dysfunction Induced by Low-Dose Bisphenol A through the CatSper-Ca2+ Signaling Pathway.

Bisphenol A (BPA), a typical endocrine disruptor, is known to have various adverse effects on the male reproductive system. However, the toxic effects and mechanisms of low-dose BPA have not yet been fully explored. In this study, male Kunming mice were orally administered low-dose BPA (0.03, 0.3 and 3 mg/kg/d) for ten consecutive weeks. Pathological sections of testicular tissue showed no significant morphological differences after BPA exposure. An analysis of the functional parameters of sperm revealed that exposure to low-dose BPA significantly decreased sperm motility, chemotaxis, and the acrosome reaction. An in vitro BPA exposure model combined with an omics data analysis showed that the olfactory receptor-related pathway was significantly enriched after BPA treatment. Subsequent experiments verified the reduced mRNA level of a novel olfactory receptor gene, Olfr25, in vivo and in vitro exposure models. Meanwhile, exposure to low-dose BPA reduced the intracellular calcium ion concentration and the mRNA levels of pore-forming subunits of the CatSper channel in sperm. Importantly, the knockdown of Olfr25 inhibited calcium ion levels and CatSper subunit expression in GC-2 cells. Olfr25 overexpression attenuated the BPA-induced downregulation of CatSper subunit expression in GC-2 cells. These findings indicate that Olfr25 might participate in low-dose BPA-induced sperm dysfunction by affecting the CatSper-Ca2+ signaling pathway. This study reveals a new mechanism underlying the effects of low-dose BPA on sperm function and provides a reference for assessing the safety of low-dose BPA exposure.

Transplantation of three mesenchymal stem cells for knee osteoarthritis, which cell and type are more beneficial? a systematic review and network meta-analysis.

BACKGROUND: In knee osteoarthritis (KOA), treatments involving knee injections of bone marrow-derived mesenchymal stem cells (BM-MSC), adipose tissue-derived mesenchymal stem cells (AD-MSC), or umbilical cord-derived mesenchymal stem cells (UC-MSC) have shown promise in alleviating symptoms. However, which types of mesenchymal stem cells (MSCs) have the best therapeutic outcomes remain uncertain. METHOD: We systematically searched PubMed, OVID, Web of Science, and the Cochrane Library until January 1, 2024. The study evaluated five endpoints: Visual Analog Score (VAS) for Pain, Range of Motion (ROM), Whole-Organ Magnetic Resonance Imaging Score (WORMS), Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), and adverse events (ADs). Standard meta-analysis and network meta-analysis were performed using Stata 16.0. RESULTS: Fifteen studies involving 585 patients were included in the meta-analysis. Standard meta-analysis revealed significant improvements with MSCs in VAS score (P < 0.001), knee ROM (P < 0.001), and WOMAC (P < 0.016) compared to traditional therapy. In the network meta-analysis, autologous MSCs significantly improved VAS score [SMD = 2.94, 95% CI (1.90, 4.56)] and knee ROM [SMD = 0.26, 95% CI (0.08, 0.82)] compared to traditional therapy. Similarly, BM-MSC significantly improved VAS score [SMD = 0.31, 95% CI (0.11, 0.91)] and knee ROM [SMD = 0.26, 95% CI (0.08, 0.82)] compared to hyaluronic acid. However, compared with traditional therapy, autologous or allogeneic MSCs were associated with more adverse reactions [SMD = 0.11, 95% CI (0.02, 0.59)], [SMD = 0.13, 95% CI (0.002, 0.72)]. Based on the surface under the cumulative ranking results, autologous BM-MSC showed the most improvement in ROM and pain relief in KOA patients, UC-MSC (SUCRA 94.1%) were most effective for positive WORMS, and AD-MSC (SUCRA 70.6%) were most effective for WOMAC-positive patients. CONCLUSION: MSCs transplantation effectively treats KOA patients, with autologous BM-MSC potentially offering more excellent benefits.

HOXD10 attenuates renal fibrosis by inhibiting NOX4-induced ferroptosis.

In chronic kidney disease (CKD), renal fibrosis is an unavoidable result of various manifestations. However, its pathogenesis is not yet fully understood. Here, we revealed the novel role of Homeobox D10 (HOXD10) in CKD-related fibrosis. HOXD10 expression was downregulated in CKD-related in vitro and in vivo fibrosis models. UUO model mice were administered adeno-associated virus (AAV) containing HOXD10, and HOXD10 overexpression plasmids were introduced into human proximal tubular epithelial cells induced by TGF-ß1. The levels of iron, reactive oxygen species (ROS), lipid ROS, the oxidized glutathione/total glutathione (GSSG/GSH) ratio, malonaldehyde (MDA), and superoxide dismutase (SOD) were determined using respective assay kits. Treatment with AAV-HOXD10 significantly attenuated fibrosis and renal dysfunction in UUO model mice by inhibiting NOX4 transcription, ferroptosis pathway activation, and oxidative stress. High levels of NOX4 transcription, ferroptosis pathway activation and profibrotic gene expression induced by TGF-ß1/erastin (a ferroptosis agonist) were abrogated by HOXD10 overexpression in HK-2 cells. Moreover, bisulfite sequencing PCR result determined that HOXD10 showed a hypermethylated level in TGF-ß1-treated HK-2 cells. The binding of HOXD10 to the NOX4 promoter was confirmed by chromatin immunoprecipitation (ChIP) analysis and dual-luciferase reporter assays. Targeting HOXD10 may represent an innovative therapeutic strategy for fibrosis treatment in CKD.

Lipo/TK-CDN/TPP/Y6 nanoparticles inhibit cutaneous melanoma formation.

Stimulation of the innate immune stimulator of interferon genes (STING) pathway has been shown to boost anti-tumour immunity. Nevertheless, the systemic delivery of STING agonists to the tumour presents challenges. Therefore, we designed a cyclic dinucleotide (CDN)-based drug delivery system (DDS) combined photothermal therapy (PTT)/photodynamic therapy (PDT)/immunotherapy for cutaneous melanoma. We coencapsulated a reactive oxygen species (ROS)-responsive prodrug thioketone-linked CDN (TK-CDN), and photoresponsive agents chlorin E6 (Y6) within mitochondria-targeting reagent triphenylphosphonium (TPP)-modified liposomes (Lipo/TK-CDN/TPP/Y6). Lipo/TK-CDN/TPP/Y6 exhibited a photothermal effect similar to Y6, along with a superior cellular uptake rate. Upon endocytosis by B16F10 cells, Lipo/TK-CDN/TPP/Y6 generated large amounts of ROS under laser irradiation for PDT. Mice bearing B16F10 tumours were intravenously injected with Lipo/TK-CDN/TPP/Y6 and exposed to irradiation, resulting in a substantial inhibition of tumour growth. Exploration of the mechanism of anti-tumour action showed that Lipo/TK-CDN/TPP/Y6 had a stronger stimulation of STING activation and anti-tumour immune cell infiltration compared to other groups. Hence, the Lipo/TK-CDN/TPP/Y6 nanoparticles offer great potential as a DDS for targeted and on-demand drug release at tumour sites. These nanoparticles exhibit promise as a candidate for precise and controllable combination therapy in the treatment of tumours.

Identification of two novel B cell epitopes on E184L protein of African swine fever virus using monoclonal antibodies.

African swine fever virus (ASFV) is a large double-stranded DNA virus with a complex structural architecture and encodes more than 150 proteins, where many are with unknown functions. E184L has been reported as one of the immunogenic ASFV proteins that may contribute to ASFV pathogenesis and immune evasion. However, the antigenic epitopes of E184L are not yet characterized. In this study, recombinant E184L protein was expressed in prokaryotic expression system and four monoclonal antibodies (mAbs), designated as 1A10, 2D2, 3H6, and 4C10 were generated. All four mAbs reacted specifically with ASFV infected cells. To identify the epitopes of the mAbs, a series of overlapped peptides of E184L were designed and expressed as maltose binding fusion proteins. Accordingly, the expressed fusion proteins were probed with each E184L mAb separately by using Western blot. Following a fine mapping, the minimal linear epitope recognized by mAb 1A10 was identified as 119IQRQGFL125, and mAbs 2D2, 3H6, and 4C10 recognized a region located between 153DPTEFF158. Alignment of amino acids of E184L revealed that the two linear epitopes are highly conserved among different ASFV isolates. Furthermore, the potential application of the two epitopes in ASFV diagnosis was assessed through epitope-based ELISA using 24 ASFV positive and 18 negative pig serum and the method were able to distinguish positive and negative samples, indicating the two epitopes are dominant antigenic sites. To our knowledge, this is the first study to characterize the B cell epitopes of the antigenic E184L protein of ASFV, offering valuable tools for future research, as well as laying a foundation for serological diagnosis and epitope-based marker vaccine development.

APOA5 alleviates reactive oxygen species to promote oxaliplatin resistance in PIK3CA-mutated colorectal cancer.

Although platinum-based chemotherapy is the frontline regimen for colorectal cancer (CRC), drug resistance remains a major challenge affecting its therapeutic efficiency. However, there is limited research on the correlation between chemotherapy resistance and lipid metabolism, including PIK3CA mutant tumors. In this present study, we found that PIK3CA-E545K mutation attenuated cell apoptosis and increased the cell viability of CRC with L-OHP treatment in vitro and in vivo. Mechanistically, PIK3CA-E545K mutation promoted the nuclear accumulation of SREBP1, which promoted the transcription of Apolipoprotein A5 (APOA5). APOA5 activated the PPARγ signaling pathway to alleviate reactive oxygen species (ROS) production following L-OHP treatment, which contributed to cell survival of CRC cells. Moreover, APOA5 overexpression enhanced the stemness-related traits of CRC cells. Increased APOA5 expression was associated with PIK3CA mutation in tumor specimens and poor response to first-line chemotherapy, which was an independent detrimental factor for chemotherapy sensitivity in CRC patients. Taken together, this study indicated that PIK3CA-E545K mutation promoted L-OHP resistance by upregulating APOA5 transcription in CRC, which could be a potent target for improving L-OHP chemotherapeutic efficiency. Our study shed light to improve chemotherapy sensitivity through nutrient management in CRC.