The vascular contribution of apolipoprotein E to Alzheimer's disease.

Alzheimer's disease, the most prevalent form of dementia, imposes a substantial societal burden. The persistent inadequacy of disease-modifying drugs targeting amyloid plaques and neurofibrillary tangles suggests the contribution of alternative pathogenic mechanisms. A frequently overlooked aspect is cerebrovascular dysfunction, which may manifest early in the progression of Alzheimer's disease pathology. Mounting evidence underscores the pivotal role of the apolipoprotein E gene, particularly the apolipoprotein ε4 allele as the strongest genetic risk factor for late-onset AD, in the cerebrovascular pathology associated with Alzheimer's disease. In this review, we examine the evidence elucidating the cerebrovascular impact of both central and peripheral apolipoprotein E on the pathogenesis of Alzheimer's disease. We present a novel three-hit hypothesis, outlining potential mechanisms that shed light on the intricate relationship among different pathogenic events. Finally, we discuss prospective therapeutics targeting the cerebrovascular pathology associated with apolipoprotein E and explore their implications for future research endeavors.

Occurrence of halogenated organic contaminants in surface sediments of the Yangtze River estuary and its adjacent marine area.

Halogenated organic contaminants, such as chlorinated and brominated polycyclic aromatic hydrocarbons (Cl/Br-PAHs), are some of the most important emerging environmental pollutants. However, empirical data on Cl/Br-PAHs in estuarine and marine ecosystems are limited, rendering assessments of Cl/Br-PAH contamination in estuarine and offshore environments uncertain. Here the occurrence, sources, and ecological risks of 7 Cl-PAHs and 18 Br-PAHs were determined in surface sediments of the Yangtze River Estuary (YRE), a highly urbanized and industrialized area, and its adjacent marine area. The concentrations of Cl-PAHs ranged from 4.50 to 18.38 ng g-1 (average 7.19 ng g-1), while those of Br-PAHs ranged from 4.80 to 61.18 ng g-1 (average 14.11 ng g-1). The dominant Cl-PAH and Br-PAH in surface sediment were 9-chlorofluorene (17.79%) and 9-bromofluorene (58.49%), respectively. The distributions and compositions of Cl/Br-PAHs in the surface sediments varied considerably due to complex hydrodynamic and depositional conditions in the YRE and its adjacent marine area, as well as differences in physicochemical properties of different Cl/Br-PAHs. Positive matrix factorization revealed that the primary sources of Cl/Br-PAHs in the study area were e-waste dismantling (33.6%), waste incineration (23.2%), and metal smelting (11.0%). According to the risk quotient, the Cl/Br-PAHs in sediments posed no toxic risk to aquatic organisms.

Whole-genome resequencing reveals candidate genes associated with milk production trait in Guanzhong dairy goats.

Milk production is one of the most important economic utility of goats. Guanzhong dairy goat is a local dairy goat in Shaanxi Province of China and has high milk yield and quality. However, there are relatively few studies on molecular markers of milk production traits in Guanzhong dairy goats. In this study, we sequenced the whole genomes of 20 Guanzhong dairy goats, 10 of which had high milk yield (HM) and 10 of which had low milk yield (LM). We detected candidate signatures of selection in HM goats using Fst and π-ratio statistics and identified several candidate genes including ANPEP, ADRA1A and PRKG1 associated with milk production. Our results provide the basis for molecular breeding of milk production traits in Guanzhong dairy goats.

miRTarBase update 2022: an informative resource for experimentally validated miRNA-target interactions.

MicroRNAs (miRNAs) are noncoding RNAs with 18-26 nucleotides; they pair with target mRNAs to regulate gene expression and produce significant changes in various physiological and pathological processes. In recent years, the interaction between miRNAs and their target genes has become one of the mainstream directions for drug development. As a large-scale biological database that mainly provides miRNA-target interactions (MTIs) verified by biological experiments, miRTarBase has undergone five revisions and enhancements. The database has accumulated >2 200 449 verified MTIs from 13 389 manually curated articles and CLIP-seq data. An optimized scoring system is adopted to enhance this update's critical recognition of MTI-related articles and corresponding disease information. In addition, single-nucleotide polymorphisms and disease-related variants related to the binding efficiency of miRNA and target were characterized in miRNAs and gene 3' untranslated regions. miRNA expression profiles across extracellular vesicles, blood and different tissues, including exosomal miRNAs and tissue-specific miRNAs, were integrated to explore miRNA functions and biomarkers. For the user interface, we have classified attributes, including RNA expression, specific interaction, protein expression and biological function, for various validation experiments related to the role of miRNA. We also used seed sequence information to evaluate the binding sites of miRNA. In summary, these enhancements render miRTarBase as one of the most research-amicable MTI databases that contain comprehensive and experimentally verified annotations. The newly updated version of miRTarBase is now available at https://miRTarBase.cuhk.edu.cn/.

Amino modified nanofibers anchored to Prussian blue nanoparticles selectively remove Cs+ from water.

To improve the selective separation performance of silica nanofibers (SiO2 NFs) for cesium ions (Cs+) and overcome the defects of Prussian blue nanoparticles (PB NPs), PB/SiO2-NH2 NFs were prepared to remove Cs+ from water. Among them, 3-aminopropyltriethoxysilane (APTES) underwent an alkylation reaction with SiO2, resulting in the formation of a dense Si-O-Si network structure that decorated the surface of SiO2 NFs. Meanwhile, the amino functional groups in APTES combined with Fe3+ and then reacted with Fe2+ to form PB NPs, which anchored firmly on the aminoated SiO2 NFs surface. In our experiment, the maximum adsorption capacity of PB/SiO2-NH2 NFs was 111.38 mg/g, which was 31.5 mg/g higher than that of SiO2 NFs. At the same time, after the fifth cycle, the removal rate of Cs+ by PB/SiO2-NH2 NFs adsorbent was 75.36% ± 3.69%. In addition, the adsorption isotherms and adsorption kinetics of PB/SiO2-NH2 NFs were combined with the Freundlich model and the quasi-two-stage fitting model, respectively. Further mechanism analysis showed that the bond between PB/SiO2-NH2 NFs and Cs+ was mainly a synergistic action of ion exchange, electrostatic adsorption and membrane separation.

Recent advances of small extracellular vesicle biomarkers in breast cancer diagnosis and prognosis.

Current clinical tools for breast cancer (BC) diagnosis are insufficient but liquid biopsy of different bodily fluids has recently emerged as a minimally invasive strategy that provides a real-time snapshot of tumour biomarkers for early diagnosis, active surveillance of progression, and post-treatment recurrence. Extracellular vesicles (EVs) are nano-sized membranous structures 50-1000 nm in diameter that are released by cells into biological fluids. EVs contain proteins, nucleic acids, and lipids which play pivotal roles in tumourigenesis and metastasis through cell-to-cell communication. Proteins and miRNAs from small EVs (sEV), which range in size from 50-150 nm, are being investigated as a potential source for novel BC biomarkers using mass spectrometry-based proteomics and next-generation sequencing. This review covers recent developments in sEV isolation and single sEV analysis technologies and summarises the sEV protein and miRNA biomarkers identified for BC diagnosis, prognosis, and chemoresistance. The limitations of current sEV biomarker research are discussed along with future perspective applications.

HNRNPA2B1-mediated m6A modification of FOXM1 promotes drug resistance and inhibits ferroptosis in endometrial cancer via regulation of LCN2.

N6-methyladenosine (m6A) methylation is an extensive posttranscriptional RNA modification, and it is associated with various cellular responses, especially in tumor progression. An m6A "reader"-HNRNPA2B1 has been found oncogenic in multiple malignancies. As a key proliferation-related transcription factor, forkhead box protein M1 (FOXM1) is involved in tumorigenesis. Here, we elucidated the underlying mechanism by which HNRNPA2B1-mediated modification of FOXM1 promotes endometrial cancer (EC). The GSE115810 dataset was used to analyze the upregulated gene mRNA in late-stage EC tissues. The expression levels of HNRNPA2B1, FOXM1, and LCN2 in EC samples were shown by western blotting and qPCR. The interaction among HNRNPA2B1, FOXM1, and LCN2 in EC cells was detected using bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down, RNA decay analysis, and luciferase reporter experiments. Cisplatin (DDP)-resistant EC cells were constructed using HEC-1-A and HEC-1-B cells, named HEC-1-A/DDP and HEC-1-B/DDP, respectively. Proliferation, migration, and invasiveness in treated HEC-1-A/DDP and HEC-1-B/DDP cells were detected by EdU, wound healing, and transwell assays. Ferroptosis-resistant gene expression, MDA level, and ROS level were measured. The m6A modification level in EC tissues was elevated. HNRNPA2B1 and FOXM1 levels were upregulated in EC. HNRNPA2B1 expression was positively related to FOXM1 expression in EC samples, and HNRNPA2B1 bound to the 3'UTR of FOXM1 and stabilized FOXM1 mRNA via m6A modification. FOXM1 positively regulated LCN2 expression in EC cells by binding to the LCN2 promotor. Knockdown of FOXM1 downregulated ferroptosis-resistant gene expression and increased MDA and ROS levels in DDP-resistant EC cells. Rescue assays revealed that LCN2 overexpression eliminated the effects mediated by FOXM1 knockdown on the proliferation, migration, invasiveness, and ferroptosis in DDP-resistant EC cells. In conclusion, HNRNPA2B1-mediated mA modification of FOXM1 facilitates drug resistance and inhibits ferroptosis in EC cells by upregulating LCN2 expression.

Clinical relevance of glomerular C4d deposition in children with early IgA nephropathy or Henoch-Schönlein purpura nephropathy.

BACKGROUND: Both IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephropathy (HSPN) are characterized by glomerular mesangial IgA deposition. Several large studies on adults have suggested that glomerular C4d deposition has prognostic value in IgAN. However, there are few relevant studies on the clinical value of C4d deposition in children with IgAN or HSPN. METHODS: We performed a retrospective cohort study in pediatric patients with IgAN or HSPN. Clinicopathological data were collected at the time of kidney biopsy. Kidney C4d deposition was analyzed by immunohistochemistry. The end point was defined as a ≥ 20% decrease in estimated glomerular filtration from baseline. RESULTS: We enrolled 75 children, including 36 children with IgAN and 39 with HSPN. The prevalence of C4d deposition was 36% (27/75). C4d deposition was more abundant in children with proteinuria ≥ 50 mg/kg/day (51.9% versus 20.8%, P = 0.006) or nephrotic syndrome (37.0% versus 10.4%, P = 0.006). Mesangial hypercellularity (hazard ratio [HR], 5.745, 95% confidence interval [CI], 1.670-19.761, P = 0.006) and IgM deposition (HR, 4.522, 95% CI, 1.321-15.478, P = 0.016) were associated with C4d deposition. After a median follow-up of 22 months, seven (19.4%) IgAN patients and one (2.6%) HSPN patient had decreased kidney function. In children with IgAN, positive C4d was associated with decreased kidney function (P = 0.047). CONCLUSION: Glomerular C4d deposition was associated with mesangial hypercellularity and glomerular IgM deposition in IgAN and HSPN. Glomerular C4d deposition may be a risk factor for eGFR decline in children with IgAN. A higher resolution version of the Graphical abstract is available as Supplementary information.

Simultaneous ammonium and phosphate removal with Mg-loaded chitosan carbonized microsphere: Influencing factors and removal mechanism.

A novel Mg-loaded chitosan carbonized microsphere (MCCM) was prepared for simultaneous adsorption of ammonium and phosphate in this study, through the investigation of preparation procedures, addition ratio, and preparation temperature. Pollutants removals by MCCM were more acceptable with 64.71% for ammonium and 99.26% for phosphorus, compared with chitosan carbonized microspheres (CCM), Mg-loaded chitosan hydrogel beads (MCH) and MgCl2·6H2O. Addition ratio of 0.6:1 (mchitosan: mMgCl2) and preparation temperature of 400 °C in MCCM preparation were responsible for pollutant removal and yield. The effect analysis of MCCM dosage, solution pH, pollutant concentration, adsorption mode and coexisting ions on the removal for both ammonium and phosphate indicated that pollutants removals were increased with increasing MCCM dosages, and achieved the peak at pH 8.5, but presented to be stable with Na+, K+, Ca2+, Cl-, NO3-, CO32- and SO42-, except for Fe3+.Adsorption mechanisms discussion implied that simultaneous ammonium and phosphate removal with MCCM was attributed to struvite precipitation, ion exchange, hydrogen bonding, electrostatic attraction and Mg-P complexation, suggesting that MCCM presents a new way for simultaneous concentrated ammonium and phosphate removal in wastewater treatment.

Clinical Efficacy of Different Doses of Canagliflozin Combined with Metformin in the Treatment of Type 2 Diabetes: Meta-Analysis.

Background: With social development, an aging population, and the increasing trend of obesity, type 2 diabetes (T2DM) has become one of the major problems affecting human health across the globe. Methods: Information on controlled trials was retrieved from four databases to obtain the effects of different doses of canagliflozin combined with metformin for treating T2DM. After a rigorous evaluation of the quality of the literature, data analysis was performed using RevMan 5.3 software. Results: We included 8 studies in this meta-analysis. The least square (LS) means of HbA1c and FPG in the test group were statistically lower than the control group. Our analysis revealed that the adverse reactions were not significantly different between the experimental and control groups (OR: 1.03; 95% Cl: 0.94, 1.12; P = .555). Also, we found that the urinary tract infection of the experimental group was not statistically different from the control group (OR: 0.94; 95% Cl: 0.71, 1.24; P = .648). Moreover, we identified that the blood pressure and blood lipids of the experimental group did not statistically differ from the control group. Conclusion: The meta-analysis demonstrates that high doses of canagliflozin combined with metformin may be potentially effective in patients with T2DM, as evidenced by LS means of HbA1c and FPG, and the above conclusions need to be verified by more high-quality studies.

JWA inhibits nicotine-induced lung cancer stemness and progression through CHRNA5/AKT-mediated JWA/SP1/CD44 axis.

Cigarette smoking is an independent risk factor for lung cancer. Nicotine, as an addictive substance in tobacco and e-cigarettes, is known to promote tumor progression and metastasis despite being a non-carcinogen. As a tumor suppressor gene, JWA is widely involved in the inhibition of tumor growth and metastasis and the maintenance of cellular homeostasis, including in non-small cell lung cancer (NSCLC). However, the role of JWA in nicotine-induced tumor progression remains unclear. Here, we reported for the first time that JWA was significantly downregulated in smoking-related lung cancer and associated with overall survival. Nicotine exposure reduced JWA expression in a dose-dependent manner. Gene Set Enrichment Analysis (GSEA) analysis showed the tumor stemness pathway was enriched in smoking-related lung cancer, and JWA was negatively associated with stemness molecules CD44, SOX2, and CD133. JWA also inhibited nicotine-enhanced colony formation, spheroid formation, and EDU incorporation in lung cancer cells. Mechanically, nicotine downregulated JWA expression via the CHRNA5-mediated AKT pathway. Lower JWA expression enhanced CD44 expression through inhibition of ubiquitination-mediated degradation of Specificity Protein 1 (SP1). The in vivo data indicated that JAC4 through the JWA/SP1/CD44 axis inhibited nicotine-triggered lung cancer progression and stemness. In conclusion, JWA via down-regulating CD44 inhibited nicotine-triggered lung cancer cell stemness and progression. Our study may provide new insights to develop JAC4 for the therapy of nicotine-related cancers.

Anti-müllerian hormone as a predictor for live birth among women undergoing IVF/ICSI in different age groups: an update of systematic review and meta-analysis.

PURPOSE: To update the evidence of anti-müllerian hormone (AMH) as predictive factors for live birth outcome in women undergoing assisted conception and discover the modulating effect of age. METHODS: PubMed, Embase, Medline, and Web of Science were searched for studies published until June 2021. We included studies that measured serum AMH levels and reported the subsequent live birth outcomes. Random effects models and hierarchical summary receiver operating characteristics (HSROC) models were used. The QUADAS-2 checklist was employed to assess the quality of the included studies. RESULTS: We included 27 studies (27,029 women) investigating the relationship between AMH and live birth outcome after assisted conception. The diagnostic odds ratios (DOR) from random effects models were ruled out due to high heterogeneity. Our findings suggested that AMH was associated with live birth. The DOR was 2.21 (95% CI 1.89-2.59), and 2.49 (95% CI 1.26-4.91) for studies on women with unspecified ovarian reserve and women with low ovarian reserve, respectively. The DOR of those with advanced ages was 2.50 (95% CI 1.87-2.60). For younger women, the DOR was 1.41 (95% CI 0.99-2.02). HSROCs showed that AMH had no predictive ability towards live birth in women with diminished ovarian reserve or younger age. Exclusion of Chinese cohorts lowered the heterogeneity. CONCLUSIONS: This study revealed that AMH had better prediction for live birth in advanced-age women. AMH may have implicative predictive value for assisted conception counseling of couples of advanced ages.

Quantitative study on dose distribution of Freiburg flap for keloid high-dose-rate brachytherapy based on MatriXX.

PURPOSE: To quantify the dose distribution effect of insufficient scattering conditions in keloid HDR brachytherapy with Freiburg fFlap (FF) applicator. MATERIALS AND METHODS: A phantom composed of FF applicator, MatriXX and solid water slices was designed and scanned for treatment planning. Bolus with different thicknesses were covered to offer different scatter conditions. Planar dose distributions were measured by MatriXX. The maximum value (Max), average value (Avg) and γ passing rate (3 mm/3%) were evaluated by the software MyQA Platform. RESULTS: The maximum and average doses measured by MatriXX were lower than the calculated values. The difference increased as field size decreased. The Max value, found at 0.86 cm level in the two tube case, was -20.0%, and the avg value was -11.9%. All the γ values were less than 95%. This difference gradually decreased with increasing bolus thickness and the γ values were significantly improved. CONCLUSION: MatriXX could be used for dose verification of HDR brachytherapy with an FF applicator. When the FF applicator was applied for keloid, insufficient scattering conditions would cause an insufficient target dose. This difference could be reduced by covering the bolus with different thicknesses on the applicator. The smaller the field, the thicker the bolus required.

Awareness of HPV and HPV vaccines, acceptance to vaccination and its influence factors among parents of adolescents 9 to 18 years of age in China: A cross-sectional study.

BACKGROUND: Vaccination uptake rates for adolescents are still low in China despite safe and effective human papillomavirus vaccines being available. The awareness and attitudes of parents to HPV vaccines play a decisive role in adolescents' HPV vaccination uptake. METHODS: A cross-sectional study was conducted from March, 2022 to May, 2022 using an anonymous questionnaire among parents of 9 to 18 years of age from 73 cities in 23 provinces in mainland China. Demographic characteristics of parents, their knowledge and attitudes about HPV and HPV vaccination, as well as factors influencing HPV vaccination in adolescents were assessed. RESULTS: More than two-thirds of parents heard of HPV (75.5%) and HPV vaccines (84.7%). Of these participants, mothers (83.8%) were in the majority. Parents willing to vaccinate themselves and their children against HPV were 84.9% and 87.6%, respectively. Parents were more likely to vaccinate their daughters against HPV than their sons (P < 0.001). Parents who had heard of the HPV vaccines (P = 0.028) or had vaccinated themselves (P < 0.001) were more likely to have HPV vaccination for their children. Parents who accepted the price of the HPV vaccines (P = 0.005) were more likely to have their children vaccinated against HPV. CONCLUSIONS: Children's gender, awareness of the HPV vaccines, parental HPV vaccination, and the price of the HPV vaccines are likely to be the reason for parents' vaccine hesitancy for adolescents. PRACTICE IMPLICATIONS: Nurses have a critical role in identifying parental hesitancy and providing individualized education to expand the parental awareness and knowledge and encourage on-time adolescents vaccination.

Comparison Study of Small Extracellular Vesicle Isolation Methods for Profiling Protein Biomarkers in Breast Cancer Liquid Biopsies.

Small extracellular vesicles (sEVs) are an important intercellular communicator, participating in all stages of cancer metastasis, immunity, and therapeutic resistance. Therefore, protein cargoes within sEVs are considered as a superior source for breast cancer (BC) biomarker discovery. Our study aimed to optimise the approach for sEV isolation and sEV proteomic analysis to identify potential sEV protein biomarkers for BC diagnosis. sEVs derived from BC cell lines, BC patients' plasma, and non-cancer controls were isolated using ultracentrifugation (UC), a Total Exosome Isolation kit (TEI), and a combined approach named UCT. In BC cell lines, the UC isolates showed a higher sEV purity and marker expression, as well as a higher number of sEV proteins. In BC plasma samples, the UCT isolates showed the highest proportion of sEV-related proteins and the lowest percentage of lipoprotein-related proteins. Our data suggest that the assessment of both the quantity and quality of sEV isolation methods is important in selecting the optimal approach for the specific sEV research purpose, depending on the sample types and downstream analysis.

Macrolactin R from Bacillus siamensis and its antifungal activity against Botrytis cinerea.

Botrytis cinerea is listed among the most important fungal pathogens infecting strawberries. The use of biological control agents, such as Bacillus species, offers an alternative and effective way to reduce airborne pathogens. The aim of this research was to select the macrolactin R produced by Bacillus siamensis with potential for using as biological agents against the pathogenetic fungi (Botrytis cinerea) of strawberries, and to assess the mechanisms involved. Macrolactin R had significant inhibitory effects on spore germination, germ tube elongation, and mycelial growth of Botrytis cinerea. The MICs of macrolactin R inhibitions in vitro was 12.5 mg/L and The EC50 value of NJ08-3 to Botrytis cinerea spores and mycelial was 1.93 and 2.88 mg/L, respectively. Macrolactin R impacted the membrane structure of Botrytis cinerea, resulting in changes in membrane permeability and leakage of proteins and nucleic acids, then cell death. The application of the macrolactin R of Bacillus siamensis reduced the disease severity index of gray mold on strawberries. This study demonstrated that the production of macrolactin R produced by Bacillus siamensis are involved in the antifungal activity against Botrytis cinerea.

Exploring the Strain Effect in Single Particle Electrochemistry using Pd Nanocrystals.

Tuning the surface strain of heterogeneous catalysts is recognized as a powerful strategy for tailoring their catalytic activity. However, a clear understanding of the strain effect in electrocatalysis at single-particle resolution is still lacking. Here, we explore the electrochemical hydrogen evolution reaction (HER) of single Pd octahedra and icosahedra with the same surface bounded {111} crystal facet and similar sizes using scanning electrochemical cell microscopy (SECCM). It is revealed that tensilely strained Pd icosahedra display significantly superior HER electrocatalytic activity. The estimated turnover frequency at -0.87 V vs RHE on Pd icosahedra is about two times higher than that on Pd octahedra. Our single-particle electrochemistry study using SECCM at Pd nanocrystals unambiguously highlights the importance of tensile strain on electrocatalytic activity and may offer new strategy for understanding the fundamental relationship between surface strain and reactivity.

Intracellular miRNA-Triggered Surface-Enhanced Raman Scattering Imaging and Dual Gene-Silencing Therapy of Cancer Cell.

Development of theranostic nanosystems integrating cascaded surface-enhanced Raman scattering (SERS) imaging and gene silencing therapy for accurate cancer diagnosis and treatment is still a big challenge and rarely reported. Herein, a novel Au nanoparticles (AuNPs)-based theranostic nanosystem containing AuNP-Ys and AuNP-Ds for highly sensitive and specific cancer diagnosis and treatment was proposed for cascaded SERS imaging of intracellular cancer-related miR-106a and miR-106a-triggered DNAzyme-based dual gene-silencing therapy of cancer cells. The AuNP-Ys were prepared by modifying the AuNPs with specially designed Y-motifs, and the AuNP-Ds were obtained by colabeling Raman molecules and dsDNA linkers on AuNPs. When identifying the intracellular cancer-related miRNAs, the Y-motifs and dsDNA linkers undergoes miRNA-triggered ATP-driven conformational transitions and releases the miRNA for recycling, which results in the formation of AuNP network nanostructures to generate significantly enhanced SERS signals for sensitive identification of the cancer cells as well as the amplification and specific activation of DNAzymes to catalyze the Mg2+-assisted cleavage of the Survivin and c-Jun mRNAs for effective dual gene-silencing therapy of cancer cells. The AuNP-based theranostic nanosystem achieves the synergism of target-triggered SERS imaging and DNAzyme-based dual gene-silencing therapy with enhanced specificity, sensitivity, and curative effect, which can be a powerful tool for accurate diagnosis and efficient treatment of cancers.

Single-Crystalline Cathodes for Advanced Li-Ion Batteries: Progress and Challenges.

Single-crystalline cathodes are the most promising candidates for high-energy-density lithium-ion batteries (LIBs). Compared to their polycrystalline counterparts, single-crystalline cathodes have advantages over liquid-electrolyte-based LIBs in terms of cycle life, structural stability, thermal stability, safety, and storage but also have a potential application in solid-state LIBs. In this review, the development history and recent progress of single-crystalline cathodes are reviewed, focusing on properties, synthesis, challenges, solutions, and characterization. Synthesis of single-crystalline cathodes usually involves preparing precursors and subsequent calcination, which are summarized in the details. In the following sections, the development issues of single-crystalline cathodes, including kinetic limitations, interfacial side reactions, safety issues, reversible planar gliding and micro-cracking, and particle size distribution and agglomeration, are systematically analyzed, followed by current solutions and characterization techniques. Finally, this review is concluded with proposed research thrusts for the future development of single-crystalline cathodes.

Novel γδ T cell-based prognostic signature to estimate risk and aid therapy in hepatocellular carcinoma.

BACKGROUND: Numerous studies have revealed that gamma delta (γδ) T cell infiltration plays a crucial regulatory role in hepatocellular carcinoma (HCC) development. Nonetheless, a comprehensive analysis of γδ T cell infiltration in prognosis evaluation and therapeutic prediction remains unclear. METHODS: Multi-omic data on HCC patients were obtained from public databases. The CIBERSORT algorithm was applied to decipher the tumor immune microenvironment (TIME) of HCC. Weighted gene co-expression network analysis (WGCNA) was performed to determine significant modules with γδ T cell-specific genes. Kaplan-Meier survival curves and receiver operating characteristic analyses were used to validate prognostic capability. Additionally, the potential role of RFESD inhibition by si-RFESD in vitro was investigated using EdU and CCK-8 assays. RESULTS: A total of 16,421 genes from 746 HCC samples (616 cancer and 130 normal) were identified based on three distinct cohorts. Using WGCNA, candidate modules (brown) with 1755 significant corresponding genes were extracted as γδ T cell-specific genes. Next, a novel risk signature consisting of 11 hub genes was constructed using multiple bioinformatic analyses, which presented great prognosis prediction reliability. The risk score exhibited a significant correlation with ICI and chemotherapeutic targets. HCC samples with different risks experienced diverse signalling pathway activities. The possible interaction of risk score with tumor mutation burden (TMB) was further analyzed. Subsequently, the potential functions of the RFESD gene were explored in HCC, and knockdown of RFESD inhibited cell proliferation in HCC cells. Finally, a robust prognostic risk-clinical nomogram was developed and validated to quantify clinical outcomes. CONCLUSIONS: Collectively, comprehensive analyses focusing on γδ T cell patterns will provide insights into prognosis prediction, the mechanisms of immune infiltration, and advanced therapy strategies in HCC.