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Betaine supplementation in dairy cattle has gained attention due to its potential benefits to production and health as a methyl donor, which can play a crucial role in the metabolism of dairy cows. The objective of the current meta-analysis was to quantify the effects of betaine supplementation on milk production, composition, beta-hydroxybutyric acid (BHBA), and non-esterified fatty acids (NEFA). A systematic literature search was carried out, all relevant studies were retrieved, and the meta-analysis was carried out. The mean difference (MD) for dry matter intake (DMI) using the random-effects model was 0.499 kg/day (P < 0.0001). The subgroup analysis indicated that supplementing betaine in heat-stressed cows increased DMI by 0.584 kg/day (P < 0.001), while in cows not exposed to heat stress, DMI was increased by 0.381 kg/day (P = 0.007). The energy-corrected milk (ECM) increased by 1.36 kg/day (P < 0.0001). The milk fat yield was significantly increased in betaine-supplemented cows (MD = 0.040 kg/day, 95% CI = 0.015 to 0.065). The milk protein yield (kg/day) (MD = 0.014, P = 0.138) was increased (MD = 0.035, P = 0.0005) by betaine supplementation. The lactose yield (kg/day) was also significantly higher (MD = 0.055, P = 0.020) in betaine-supplemented cows. The standardized mean difference (SMD) for NEFA (SMD = -0.447, 95% CI = -1.029 to 0.135, P = 0.114) and BHBA (SMD = -0.130, 95% CI = -0.491 to 0.234). In conclusion, the findings from this meta-analysis suggest that betaine supplementation positively influences DMI, ECM, milk fat yield, milk lactose yield, and milk protein yield. Subgroup analysis further indicated that the positive effects on DMI are greater in heat-stressed cows compared to those not exposed to heat stress. The analysis did not find significant effects on the levels of NEFA or BHBA, suggesting that betaine supplementation may not directly influence these metabolic parameters.
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BACKGROUND: Sepsis, a complex and life-threatening disease, poses a significant global burden affecting over 48 million individuals. Recently, it has been reported that programmed death-ligand 1 (PD-L1) expressed on neutrophils is involved in both inflammatory organ dysfunction and immunoparalysis in sepsis. However, there is a dearth of strategies to specifically target PD-L1 in neutrophils in vivo. METHODS: We successfully developed two lipid nanoparticles (LNPs) specifically targeting neutrophils by delivering PD-L1 siRNA via neutrophil-specific antibodies and polypeptides. In vivo and in vitro experiments were performed to detect lipid nanoparticles into neutrophils. A mouse cecal ligation and puncture (CLP) model was used to detect neutrophil migration, neutrophil extracellular traps (NETs) level, and organ damage. RESULT: The PD-L1 siRNA-loaded LNPs that target neutrophils suppressed inflammation, reduced the release of NETs, and inhibited T-lymphocyte apoptosis. This approach could help maintain homeostasis of both the immune and inflammatory responses during sepsis. Furthermore, the PD-L1 siRNA-loaded LNPs targeting neutrophils have the potential to ameliorate the multi-organ damage and lethality resulting from CLP. CONCLUSIONS: Taken together, our data identify a previously unknown drug delivery strategy targeting neutrophils, which represents a novel, safe, and effective approach to sepsis therapy.
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Compressed ultrafast photography (CUP) can capture irreversible or difficult-to-repeat dynamic scenes at the imaging speed of more than one billion frames per second, which is obtained by compressive sensing-based image reconstruction from a compressed 2D image through the discretization of detector pixels. However, an excessively high data compression ratio in CUP severely degrades the image reconstruction quality, thereby restricting its ability to observe ultrafast dynamic scenes with complex spatial structures. To address this issue, a discrete illumination-based CUP (DI-CUP) with high fidelity is reported. In DI-CUP, the dynamic scenes are loaded into an ultrashort laser pulse train with controllable sub-pulse number and time interval, thus the data compression ratio, as well as the overlap between adjacent frames, is greatly decreased and flexibly controlled through the discretization of dynamic scenes based on laser pulse train illumination, and high-fidelity image reconstruction can be realized within the same observation time window. Furthermore, the superior performance of DI-CUP is verified by observing femtosecond laser-induced ablation dynamics and plasma channel evolution, which are hardly resolved in the spatial structures using conventional CUP. It is anticipated that DI-CUP will be widely and dependably used in the real-time observations of various ultrafast dynamics.
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Coking industry is usually regarded as a high pollution and high energy consumption industry. China is accelerating its efforts to reduce pollution and carbon emissions in the industrial sector, which has received little attention as the world's largest producer of coke. Therefore, in this study, the trend of air pollution and carbon emissions in China's coking industry and the path of coordinated emission reduction were studied. The results indicate that the average annual emissions of PM, SO2, NOx, VOCs, and CO2 in China's coking industry from 2012 to 2022 amount to 205.98, 69.47, 193.45, 599.80 Gg and 191.10 Tg, respectively. The main sources of PM, SO2, NOx, VOCs and CO2 in coking industry were coal preparation (51.5 %), charge and pushing (39.5 %), coke oven gas (99.8 %), byproduct recovery (47.0 %) and fuel combustion (87.5 %). The emissions from coking plants in central and southern Shanxi, eastern and southern Hebei, and central Shandong are the most concentrated. Ultra-low emission transformation and deep treatment of VOCs have greatly reduced pollutant emissions in key areas of air pollutant control, but the actual emission reduction effect of these measures has been weakened by the additional emissions caused by the increase of coke production in other non-key areas. The research on synergetic emission reduction path shows that there is a great synergistic benefit between air pollutants and CO2 emission reduction in coking industry. It is estimated that the APeq (air pollutants and carbon equivalent) of China's coking industry in 2025, 2028 and 2030 will decrease by 38.2 %, 63.5 % and 70.8 % respectively compared with 2022. With the continuous promotion of pollution reduction and carbon reduction measures, the emission reduction potential of China's coking industry will gradually shift from key areas to non-key areas.
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Optical frequency division based on bulk or fiber optics provides unprecedented spectral purity for microwave oscillators. To extend the applications of this approach, the challenges are to develop miniaturized oscillators without trading off phase noise performance. Here, we report a chip-scale high-performance photonic microwave oscillator based on integrated electro-optical frequency division. Dual distributed-feedback lasers are co-self-injection locked to a single silicon nitride spiral resonator to provide a record-high-stability, fully on-chip optical reference. An integrated electro-optical frequency comb based on a thin-film lithium niobate phase modulator chip is leveraged to perform optical-to-microwave frequency division. The resulting integrated photonic microwave oscillator achieves a record-low phase noise for chip-scale oscillators. The results represent a major advance in high-performance, integrated photonic microwave oscillators for applications including signal processing, radar, timing, and coherent communications.
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Both concurrent chemoradiotherapy (CCRT) and induction chemotherapy (ICT) followed by CCRT are standard care of advanced nasopharyngeal carcinoma (NPC). However, tailoring personalized treatment is lacking. Herein, we established a radiogenomic clinical decision support system to classify patients into three subgroups according to their predicted disease-free survival (DFS) with CCRT and ICT response. The CCRT-preferred group was suitable for CCRT since they achieved good survival with CCRT, which could not be improved by ICT. The ICT-preferred group was suitable for ICT plus CCRT since they had poor survival with CCRT; additional ICT could afford an improved DFS. The clinical trial-preferred group was suitable for clinical trials since they exhibited poor survival regardless of receiving CCRT or ICT plus CCRT. These findings suggest that our radiogenomic clinical decision support system could identify optimal candidates for CCRT, ICT plus CCRT, and clinical trials, and may thus aid in personalized management of advanced NPC.
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BACKGROUND: Cancer-associated fibroblasts (CAFs) are one of the major components of prostate stromal cells, which play a crucial part in tumor development and treatment resistance. This study aimed to establish a model of CAFs-related microRNAs (miRNAs) to assess prognostic differences, tumor microenvironments, and screening of anticancer drugs by integrating data from single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (buRNA-seq). METHODS: scRNA-seq and buRNA-seq data of primary prostate cancer (PCa) were downloaded from Gene Expression Omnibus and The Cancer Genome Atlas databases. Statistical methods including Least absolute shrinkage and selection operator (Lasso), Lasso penalized, Random Forest, Random Forest Combination, and Support Vector Machine (SVM) were performed to select hub miRNAs. Pathway analyses and assessment of infiltrating immune cells were conducted using Gene Set Enrichment Analysis and the CIBERSORT algorithm. The expression of CAFs-related miRNAs in fibroblast cell lines were validated through quantitative real-time PCR. Cell Counting Kit 8 (CCK8), wound-healing, clone formation, and cell migration assays were used to explore cell proliferation, growth, and migration in vitro. A mouse xenograft model was established to investigate the effect of CAFs on tumor growth in vivo. RESULTS: Through single-cell transcriptomics analysis in 34 PCa patients, 89 CAFs-related mRNAs were identified. A prognostic model based on 9 CAFs-related miRNAs (hsa-miR-1258, hsa-miR-133b, hsa-miR-222-3p, hsa-miR-145-3p, hsa-miR-493-5p, hsa-miR-96-5p, hsa-miR-15b-5p, hsa-miR-106b-5p, and hsa-miR-191-5p) was established to predict biochemical recurrence (BCR). We have determined through two prediction methods that NVP-TAE684 may be the optimal targeted therapy drug for treating CAFs. Downregulation of hsa-miR-106b-5p in CAFs significantly suppressed cell proliferation, migration, and colony formation in vitro. In vivo studies using a xenograft model further confirmed that hsa-miR-106b-5p downregulation significantly reduced tumor growth. CONCLUSION: Our findings conducted an integrated bioinformatic analysis to develop a CAFs-related miRNAs model that provides prognostic insights into individualized and precise treatment for prostate adenocarcinoma patients. Downregulation of miR-106b-5p in CAFs significantly suppressed tumor growth, suggesting a potential therapeutic target for cancer treatment.
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Background: Electroacupuncture (EA) has been shown to promote functional recovery after cerebral ischemia-reperfusion (I/R) injury. However, the contribution of mitochondrial dynamics to recovery remains unclear. The aim of this study was to investigate whether mitochondrial dynamics are involved in the effects of EA on cerebral I/R injury. Methods: The rats with cerebral I/R injury were established by the middle cerebral artery occlusion/reperfusion. Subsequently, EA was applied to Baihui (GV20) and Dazhui (GV14) acupoints, with 2 Hz/5 Hz in frequency, 1.0 mA in intensity, 20 min each time, once a day for seven consecutive days. The therapeutic outcomes were assessed by modified neurological severity score (mNSS), 2,3,5-Triphenyte-trazolium chloride (TTC) staining, and hematoxylin-eosin (HE) staining. Mitochondrial morphology was observed under transmission electron microscopy. Adenosine triphosphate (ATP) content and ATP synthases (ATPases) activity were evaluated to measure mitochondrial function using ELISA. Finally, mitochondrial dynamics-related molecules, including dynamin-related protein 1 (Drp1), fission 1 (Fis1), mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and optic atrophy 1 (OPA1), were detected by Western blot and immunofluorescence staining. Results: Cerebral I/R injury induced neurological dysfunction, cerebral infarction and neuronal injury, all of which were ameliorated by EA. And EA improved mitochondrial morphology and function. Moreover, EA altered the balance of mitochondrial dynamics. Specifically, the data showed a significant decrease in the expression of Drp1 and Fis1, leading to the inhibition of mitochondrial fission. Additionally, Mfn1, Mfn2 and Opa1, which are related to mitochondrial fusion, were effectively promoted after EA treatment. However, sham EA did not show any neuroprotective effects in rats with cerebral I/R injury. Conclusions: In summary, our study indicates that the balance of mitochondrial dynamics is crucial for EA therapy to treat cerebral I/R injury.
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Dietary antioxidants may have beneficial effects on bone health, but it remains uncertain in children and adolescents. This study investigates the association of composite dietary antioxidant index (CDAI) with bone mineral density (BMD) in children and adolescents aged 8-19 years from the National Health and Nutrition Examination Survey (NHANES) 2007-2010. The study assessed the relationship between CDAI and BMD in 2994 individuals aged 8-19 years (average age 13.48 ± 3.32 years) from the NHANES 2007-2010. Multivariate linear regression analyses were utilized to detect the association between CDAI and total spine, femur neck, and total femur BMD, adjusting for confounders including age, race/ethnicity, sex, poverty income ratio (PIR), body mass index (BMI), serum phosphorus and calcium. Stratified analyses and interaction tests were performed to examine the stability of the results. The weighted characteristics showed that subjects in the fourth CDAI quartile were more likely to be older, men, and Non-Hispanic White. They have higher values of serum total calcium and phosphorus. After adjusting all confounders, CDAI was positively associated with the total spine (ß = 0.0031 95% CI 0.0021-0.0040), total femur (ß = 0.0039 95% CI 0.0028-0.0049), and femur neck BMD (ß = 0.0031 95% CI 0.0021-0.0040) in children and adolescents. Furthermore, we found no interaction effects between different race/ethnicity, age, and sex groups. Our findings suggest that dietary intake of multiple antioxidants was positively associated with BMD in children and adolescents. These findings provide valuable evidence for improving bone health in the early stages of life. However, more prospective studies are required to validate our findings and their causal relationship.
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Antioxidantes , Densidade Óssea , Inquéritos Nutricionais , Humanos , Adolescente , Criança , Feminino , Masculino , Antioxidantes/metabolismo , Adulto Jovem , Dieta , Colo do FêmurRESUMO
A series of amino acid ester trifluoroacetate derivatives was synthesized from scaberol C. They were screened for their inhibitory activity against Non-Small Cell Lung Cancer (NSCLC) cells. Among them, compound 2 l showed significant cytotoxicity against A549 and H460 cells (IC50), and was more active than cisplatin (DDP). The epidermal growth factor receptor (EGFR) was overexpressed in NSCLC, which was the target of multiple cancer therapies and a strong prognostic indicator. Our previous studies reported that the target of scaberol C derivatives against NSCLC cells was EGFR. And then molecular docking analysis and molecular dynamics (MD) simulations indicated that 2 l can stably and covalently bind to the EGFR target protein.
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Cembranolides are characteristic metabolites in marine soft corals, with complex structures and widespread biological activities. However, seldom has an intensive pharmacological study been done for these intriguing marine natural products. In this work, systematic chemical investigation was performed on Sinularia pedunculata by HSQC-based small molecule accurate recognition technology (SMART), resulting in the isolation and identification of 31 cembrane-type diterpenoids, including six new ones. In the bioassay, several compounds showed significant anti-inflammatory activities on the inhibition of NO production. The structure-activity relationship (SAR) was comprehensively analyzed, and two most bioactive and less toxic compounds 8 and 9 could inhibit inflammation through suppressing NF-κB and MAPK signaling pathways, and reduce the secretion of inflammatory cytokines. In a mouse model of dextran sodium sulfate (DSS)-induced acute colitis, 8 and 9 exhibited good anti-inflammatory effects and the ability to repair the colon epithelium, giving insight into the application of cembranolides as potential ulcerative colitis (UC) agents.
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Antozoários , Colite Ulcerativa , Sulfato de Dextrana , Diterpenos , Animais , Colite Ulcerativa/tratamento farmacológico , Diterpenos/farmacologia , Diterpenos/química , Diterpenos/uso terapêutico , Diterpenos/isolamento & purificação , Camundongos , Relação Estrutura-Atividade , Antozoários/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/isolamento & purificação , Células RAW 264.7 , NF-kappa B/metabolismo , NF-kappa B/antagonistas & inibidores , Descoberta de Drogas , Camundongos Endogâmicos C57BL , Humanos , Masculino , Óxido Nítrico/metabolismoRESUMO
Low-temperature KSCN molten salt is a promising technique to synthesize defect-rich MoS2catalysts for hydrogen evolution reaction (HER). However, owing to the fast ion diffusion rate for rapid crystal growth, the resultant catalysts show a morphology of microsphere, which aggregates from MoS2nanosheets, to suppress the catalytic performance. In this work, large-sized few-layer MoS2nanosheets are synthesized via a spatial confinement strategy by adding inert NaCl into the KSCN molten salt. With the NaCl spacer to physically block the long-distance ion diffusion and isolate the chemical reaction, the MoS2nucleation and subsequent crystal growth could be controlled, guiding the nanosheets to grow along the narrow gap between the NaCl crystals to avoid aggregation. As a result, ultrathin MoS2nanosheets with a large geometry size are constructed. Profiting from the architecture to expose active sites and boost charge transfer kinetics, the large-sized few-layer MoS2nanosheets exhibit an impressive HER performance, showing a smallη10of 160 mV and a low Tafel slope of 53 mV dec-1with excellent stability. This work provides not only an efficient HER catalyst but also a facile spatial confinement technique to design and synthesize a large spectrum of transition metal sulfides for broad uses.
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BACKGROUND: This study aimed to investigate the clinical efficacy of intra-articular injections of medical chitosan for treating knee osteoarthritis (KOA) and measure the lipid metabolism profiles of the synovial tissue. METHODS: 60 patients with KOA undergoing conservative treatment were recruited and randomized into two groups: one without pharmacological intervention (OA group) and the other receiving course-based intra-articular medical chitosan injections (CSI group). Quantitative lipidomic profile of synovial tissue was analyzed. Functional scores, including Kellgren-Lawrence rating (K-L), VAS, WOMAC scoring, and AKS scoring were conducted. RESULTS: Survival from the initial conservative treatment to final knee arthroplasty was significantly longer in the CSI group compared to the OA group. Except for the pre-surgery VAS score, no statistically significant differences were observed in the other scores, including K-L, initial VAS, WOMAC, and AKS. However, the CSI group experienced a slightly more pronounced decline in AKS-Knee subscores compared to the OA group. Compared to the CSI group, the OA group exhibited a significant upregulation in most differential lipids, particularly triacylglycerides (TAGs, 77%). The OA group had notably higher levels of long-chain unsaturated fatty acids. CONCLUSION: Intra-articular injection of medical chitosan significantly prolongs the survival period before knee arthroplasty and reduces the deposition of TAGs metabolites.
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Increasing the number of teats in sheep helps to improve the survival rate of sheep lambs after birth. In order to analyze the candidate genes related to the formation of multiple teats in Hu sheep, the present study was conducted to investigate the genetic pattern of multiple teats in Hu sheep. In this study, based on genome-wide data from 157 Hu sheep, Fst, xp-EHH, Pi and iHS signaling were performed, and the top 5% signal regions of each analyzed result were annotated based on the Oar_v4.0 for sheep. The results show that a total of 142 SNP loci were selected. We found that PTPRG, TMEM117 and LRP1B genes were closely associated with polypodium formation in Hu sheep, in addition, among the candidate genes related to polypodium we found genes such as TMEM117, SLC25A21 and NCKAP5 related to milk traits. The present study screened out candidate genes for the formation of multiple teats at the genomic level in Hu sheep.
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Polimorfismo de Nucleotídeo Único , Animais , Ovinos/genética , Polimorfismo de Nucleotídeo Único/genética , Feminino , Estudo de Associação Genômica Ampla/veterináriaRESUMO
This systematic review and meta-analysis aimed to compare perioperative and oncologic outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) treated with robotic-assisted surgery versus open laparotomy. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized controlled trials (RCTs) and cohort studies up to June 15, 2024, were identified using PubMed, EMBASE, and Google Scholar. Additionally, reference lists of included studies, relevant review articles, and clinical guidelines were manually searched. The primary outcomes evaluated were length of stay, 90-day mortality, postoperative pancreatic fistula (POPF), and Post-pancreatectomy haemorrhage (PPH). Secondary outcomes included estimated blood loss, reoperation rate, lymph node yield, and operative time. The final analysis included 10 retrospective cohort studies involving 23,272 patients (2,179 robotic-assisted and 21,093 open surgery). There were no significant differences between the two procedures in terms of postoperative pancreatic fistula, Post-pancreatectomy haemorrhage, lymph node yield, and operative time. However, patients undergoing robotic-assisted surgery had shorter lengths of stay, lower 90-day mortality, and less estimated blood loss compared to those undergoing open surgery. The reoperation rate was higher for the robotic-assisted group. Robotic-assisted surgery for pancreatic ductal adenocarcinoma is safe and feasible. Compared to open surgery, it offers better perioperative and short-term oncologic outcomes, but with a higher risk of reoperation.
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Carcinoma Ductal Pancreático , Tempo de Internação , Pancreatectomia , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Humanos , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/mortalidade , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/mortalidade , Pancreatectomia/métodos , Resultado do Tratamento , Tempo de Internação/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Duração da Cirurgia , Fístula Pancreática/etiologia , Fístula Pancreática/epidemiologia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Reoperação/estatística & dados numéricos , Laparotomia/métodosRESUMO
The effect and mechanism of Huangqin Qingre Chubi Capsules(HQC) on rheumatoid arthritis(RA) were studied.Seventy male SPF rats were randomly divided into normal group, model group, low-(0. 18 g·kg~(-1)), middle-(0. 36 g·kg~(-1)), and high-(0. 72 g·kg~(-1)) dose groups of HQC, methotrexate group(MTX, 0. 75 mg·kg~(-1)), and negative control group(NC group, model +saline). Adjuvant arthritis fibroblast-like synoviocytes(AA-FLS) were divided into normal group, model group, low-, middle-, and high-dose groups of HQC, and negative control group. RT-qPCR and Western blot were used to detect the m RNA and protein expressions of METTL3, SFRP4, ß-catenin, CCND1, c-Myc, MMP3, and fibronectin. The protein expression of MMP3 and ß-catenin was detected by immunofluorescence. The gene expression level of METTL3 on AA-FLS was knocked down to further examine the expression of each gene. ELISA measured the levels of IL-1ß, IL-6, and IL-8. The results showed that compared with the normal group, rats in the model group found redness and swelling in their limbs and significantly increased joint swelling. Compared with the model group, the joint swelling degree of each treatment group significantly decreased(P<0. 05). The paw retraction threshold and body weight mass index both significantly increased(P<0. 05). METTL3 was highly expressed on AA and negatively correlated with the expression of SFRP4. After treatment, the m RNA and protein expression of METTL3, ß-catenin, CCND1, c-Myc, fibronectin, and MMP3 were significantly decreased on AA-FLS(P< 0. 05). Compared with the model group, knocking down METTL3 resulted in reduced m RNA and protein expression of ß-catenin, CCND1, c-Myc, fibronectin, and MMP3(P< 0. 05). At the same time, the m RNA and protein expressions of ß-catenin, CCND1, c-Myc, fibronectin, and MMP3 in the HQC+METTL3 knockdown group were significantly lower than those in the METTL3 knockdown group(P<0. 05). HQC could reduce the levels of IL-1ß, IL-6, and IL-8 to varying degrees(P<0. 05). The results indicate that HQC has a significant improvement effect on arthritis in AA rats. The expression of METTL3 is significantly increased in synovial tissue and AA-FLS of AA rats, which may be a potential target for the diagnosis and treatment of RA. HQC improves RA through the METTL3-SFRP4/Wnt/ß-catenin signaling pathway and has significant antiinflammatory and anti-rheumatic effects.
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Artrite Reumatoide , Cápsulas , Medicamentos de Ervas Chinesas , Via de Sinalização Wnt , beta Catenina , Animais , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Artrite Reumatoide/genética , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Ratos , Masculino , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo , beta Catenina/genética , Metiltransferases/genética , Metiltransferases/metabolismo , Humanos , Ratos Sprague-Dawley , Sinoviócitos/efeitos dos fármacos , Sinoviócitos/metabolismo , Proteínas Proto-OncogênicasRESUMO
Despite docetaxel combined with cisplatin and 5-fluorouracil (TPF) being the established treatment for advanced nasopharyngeal carcinoma (NPC), there are patients who do not respond positively to this form of therapy. However, the mechanisms underlying this lack of benefit remain unclear. DCAF7 is identified as a chemoresistance gene attenuating the response to TPF therapy in NPC patients. DCAF7 promotes the cisplatin resistance and metastasis of NPC cells in vitro and in vivo. Mechanistically, DCAF7 serves as a scaffold protein that facilitates the interaction between USP10 and G3BP1, leading to the elimination of K48-linked ubiquitin moieties from Lys76 of G3BP1. This process helps prevent the degradation of G3BP1 via the ubiquitinâproteasome pathway and promotes the formation of stress granule (SG)-like structures. Moreover, knockdown of G3BP1 successfully reversed the formation of SG-like structures and the oncogenic effects of DCAF7. Significantly, NPC patients with increased levels of DCAF7 showed a high risk of metastasis, and elevated DCAF7 levels are linked to an unfavorable prognosis. The study reveals DCAF7 as a crucial gene for cisplatin resistance and offers further understanding of how chemoresistance develops in NPC. The DCAF7-USP10-G3BP1 axis contains potential targets and biomarkers for NPC treatment.
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Severe shuttle effect of soluble polysulfides and sluggish redox kinetics have been thought of as the critical issues hindering the extensive applications of lithium-sulfur batteries (LSBs). Herein, one-dimensional boron nitride (1D BN) fibers with abundant pores and sufficient N-vacancy defects were synthesized using a thermal crystallization following a pre-condensation step. The 1D structure of BN facilitates unblocked ions diffusion pathways during charge/discharge cycles. The embedded pores within the polar BN strengthen the immobilization of polysulfides via both physical confinement and chemical interaction. Moreover, the highly exposed active surface area and intentionally created N-vacancy sites substantially promote reaction kinetics by lowering the energy barriers of the rate-limiting steps. After incorporating with conductive carbon networks and elemental S, the as-prepared S/Nv-BN@CBC cathode of LSBs deliver an initial discharge capacity of up to 1347 mAh g-1 at 200 mA g-1, while maintaining a low decay rate of 0.03% per cycle over 1000 cycles at 1600 mA g-1. This work offers an effective strategy to mitigate the shuttle effect and highlights the significant potential of defect-engineered BN in accelerating the reaction kinetics of LSBs.
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Multiple cell death pathways are involved in neuronal death in ischemic stroke (IS). However, the role of different cell death pathways in different cell types has not been elucidated. By analyzing three single-nucleus RNA sequencing (snRNA-seq) data of IS, we first found that a variety of programmed cell death (PCD) -related genes were significantly changed in different cell types. Based on machine learning and virtual gene knockout, we found that ferroptosis related genes, ferritin heavy chain 1 (Fth1) and ferritin light chain (Ftl1), play a key role in IS. Ftl1 and Fth1 can promote microglia activation, as well as the production of inflammatory factors and chemokines. Cell communication analysis showed that activated microglia could enhance chemotactic peripheral leukocyte infiltration, such as macrophages and neutrophils, through Spp1-Cd44 and App-Cd74 signaling, thereby aggravating brain tissue damage. Furthermore, real-time quantitative polymerase chain reaction (RT-qPCR) showed that P2ry12 and Mef2c were significantly decreased in oxygen-glucose deprivation (OGD) group, while Ftl1, Fth1, Apoe, Ctsb, Cd44 and Cd74 were significantly increased in OGD group. Collectively, our findings suggested targeted therapy against microglia Ftl1 and Fth1 might improve the state of microglia, reduce the infiltration of peripheral immune cells and tissue inflammation, and then improve the ischemic brain injury in mouse.