RESUMEN
Acetobacter is one of the main species producing fruit vinegar and its tolerance mechanism to citric acid has not been fully studied. This limits fruit vinegar production from high-citric-acid fruits, which are excellent materials for fruit vinegar production. This study analyzed the metabolic differences between two strains of A. tropicalis with different citric acid tolerances using non-targeted metabolomics. Differential metabolites and metabolic pathways analysis showed that the enhanced amino acid metabolism significantly improved the citric acid tolerance of A. tropicalis and the deamination of amino acids may also play a role. In addition, the up-regulated phosphatidylcholine (PC) and N-heptanoylhonoserine lactone indicated decreased membrane permeability and enhanced quorum sensing (QS), respectively. The analysis of the interaction between pathways and metabolites indicated that Gln, Cys, and Tyr contribute to improving citric acid tolerance, which was also confirmed by the exogenous addition. After adding the amino acids, the down-regulated qdh, up-regulated ggt, and improved glutathione reductase (GR) activity in J-2736 indicated that glutathione metabolism played an important role in resisting citric acid, and cellular antioxidant capacity was increased. This study provides a theoretical basis for efficient fruit vinegar production from citric-acid-type fruits.
Asunto(s)
Ácido Acético , Acetobacter , Antioxidantes , Ácido Cítrico , Glutatión , Acetobacter/metabolismo , Acetobacter/efectos de los fármacos , Ácido Cítrico/metabolismo , Ácido Acético/metabolismo , Ácido Acético/farmacología , Antioxidantes/metabolismo , Glutatión/metabolismo , Frutas/microbiología , Frutas/metabolismo , Aminoácidos/metabolismo , Percepción de Quorum , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Metabolómica , Redes y Vías MetabólicasRESUMEN
Nonionic surfactant aerosols play a crucial role in many industries, but they can cause acute irritation to users' eyes during spraying. This cytotoxic process is associated with corneal cell necrosis causing cell membrane disruption. Industrial grade surfactants are typically polydisperse mixtures described by their nominal chemical structure but how the polydispersity affects their interactions with cell membrane, remains largely unexplored. A better understanding could benefit product formulations to maximise their efficiency whilst minimising their toxicity to the users. In this study, poly-oxyethylene glycol monododecyl ethers (C12E4, C12E23) were used to form ideal binary surfactant mixtures. The cytotoxicities of mono and polydispersed surfactants towards human corneal epithelial cells were examined, followed by a series of biophysical characterisations of interactions between surfactants and model cell membranes. Notably, to probe the journey of individual C12E4 and C12E23 surfactant molecules across the cell membrane from a binary surfactant mixture, "two-colour" neutron reflection measurements were achieved via Hydrogen/Deuterium substitution. The relative distributions of C12E4 and C12E23 across cell membranes and their nanostructural conformations revealed a synergistic membrane-lytic ability initiated by surfactant mixing, with the more hydrophobic C12E4 exhibiting stronger membrane binding potency than the hydrophilic C12E23. The exact molar ratio of C12E4 against C12E23 in the mixture determined how the mixed surfactant interacted with the cell membrane, and how the process directly impacted cytotoxicity and eye irritation. Thus, the cytotoxicity of polydisperse surfactants is not the same as monodisperse surfactant of the same average structure. This work provides a useful basis for the assessment of surfactant mixing by balancing their efficiency and toxicity.
Asunto(s)
Tensoactivos , Tensoactivos/química , Tensoactivos/farmacología , Humanos , Membrana Celular/efectos de los fármacos , Membrana Celular/química , Polietilenglicoles/química , Supervivencia Celular/efectos de los fármacos , Interacciones Hidrofóbicas e Hidrofílicas , Tamaño de la Partícula , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Propiedades de Superficie , Irritantes/química , Línea CelularRESUMEN
Metabolic syndrome (MetS) includes cardiovascular risk factors like obesity, dyslipidemia, hypertension, and glucose intolerance, which increase the risk of overactive bladder (OAB), characterized by urgency, frequency, urge incontinence, and nocturia. Both MetS and ovarian hormone deficiency (OHD) are linked to bladder overactivity. Nitric oxide (NO) is known to reduce inflammation and promote healing but its effect on bladder overactivity in MetS and OHD is unclear. This study aimed to investigate NO's impact on detrusor muscle hyperactivity in rats with MetS and OHD. Female Sprague-Dawley rats were divided into seven groups based on diet and treatments involving L-arginine (NO precursor) and L-NAME (NOS inhibitor). After 12 months on a high-fat, high-sugar diet with or without OVX, a cystometrogram and tracing analysis of voiding behavior were used to identify the symptoms of detrusor hyperactivity. The MetS with or without OHD group had a worse bladder contractile response while L-arginine ameliorated bladder contractile function. In summary, MetS with or without OHD decreased NO production, reduced angiogenesis, and enhanced oxidative stress to cause bladder overactivity, mediated through the NF-kB signaling pathway, whereas L-arginine ameliorated the symptoms of detrusor overactivity and lessened oxidative damage via the NRF2/HIF-1α signaling pathway in MetS with or without OHD-induced OAB.
Asunto(s)
Modelos Animales de Enfermedad , Subunidad alfa del Factor 1 Inducible por Hipoxia , Síndrome Metabólico , Factor 2 Relacionado con NF-E2 , Óxido Nítrico , Ratas Sprague-Dawley , Transducción de Señal , Vejiga Urinaria Hiperactiva , Vejiga Urinaria , Animales , Óxido Nítrico/metabolismo , Vejiga Urinaria Hiperactiva/metabolismo , Vejiga Urinaria Hiperactiva/etiología , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/fisiopatología , Femenino , Factor 2 Relacionado con NF-E2/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Ratas , Síndrome Metabólico/metabolismo , Transducción de Señal/efectos de los fármacos , Vejiga Urinaria/metabolismo , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/patología , Vejiga Urinaria/fisiopatología , Arginina/farmacologíaRESUMEN
Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high mortality and drug resistance and no targeted drug available at present. Compound 4, a staurosporine alkaloid derived from Streptomyces sp. NBU3142 in a marine sponge, exhibits potent anti-TNBC activity. This research investigated its impact on MDA-MB-231 cells and their drug-resistant variants. The findings highlighted that compound 4 inhibits breast cancer cell migration, induces apoptosis, arrests the cell cycle, and promotes cellular senescence in both regular and paclitaxel-resistant MDA-MB-231 cells. Additionally, this study identified mitogen-activated protein kinase kinase kinase 11 (MAP3K11) as a target of compound 4, implicating its role in breast tumorigenesis by affecting cell proliferation, migration, and cell cycle progression.
Asunto(s)
Antineoplásicos , Apoptosis , Movimiento Celular , Proliferación Celular , Estaurosporina , Neoplasias de la Mama Triple Negativas , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Humanos , Estaurosporina/farmacología , Estaurosporina/análogos & derivados , Línea Celular Tumoral , Animales , Femenino , Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Poríferos , Streptomyces , Resistencia a Antineoplásicos/efectos de los fármacos , Quinasas Quinasa Quinasa PAM/metabolismo , Quinasas Quinasa Quinasa PAM/antagonistas & inhibidores , Senescencia Celular/efectos de los fármacosRESUMEN
Background: Trop2 (trophoblast cell-surface antigen 2) is overexpressed in multiple malignancies and is closely associated with poor prognosis, thus positioning it as a promising target for pan-cancer therapies. Despite the approval of Trop2-targeted antibody-drug conjugates (ADCs), challenges such as side effects, drug resistance, and limited efficacy persist. Recent studies have shown that the dimeric forms of Trop2 are crucial for its oncogenic functions, and the binding epitopes of existing Trop2-targeted drugs lie distant from the dimerization interface, potentially limiting their antitumor efficacy. Method: A well-established synthetic nanobody library was screened against Trop2-ECD. The identified nanobodies were extensively characterized, including their binding specificity and affinity, as well as their bioactivities in antigen-antibody endocytosis, cell proliferation, and the inhibition of Trop2 dimer assembly. Finally, ELISA based epitope analysis and AlphaFold 3 were employed to elucidate the binding modes of the nanobodies. Results: We identified two nanobodies, N14 and N152, which demonstrated high affinity and specificity for Trop2. Cell-based assays confirmed that N14 and N152 can facilitate receptor internalization and inhibit growth in Trop2-positive tumor cells. Epitope analysis uncovered that N14 and N152 are capable of binding with all three subdomains of Trop2-ECD and effectively disrupt Trop2 dimerization. Predictive modeling suggests that N14 and N152 likely target the epitopes at the interface of Trop2 cis-dimerization. The binding modality and mechanism of action demonstrated by N14 and N152 are unique among Trop2-targeted antibodies. Conclusions: we identified two novel nanobodies, N14 and N152, that specifically bind to Trop2. Importantly, these nanobodies exhibit significant anti-tumor efficacy and distinctive binding patterns, underscoring their potential as innovative Trop2-targeted therapeutics.
RESUMEN
BACKGROUND: Therapeutic tumor vaccines have emerged as a compelling avenue for treating patients afflicted with advanced prostate cancer (PCa), particularly those experiencing biochemical relapse or ineligible for surgical intervention. This study serves to consolidate recent research findings on therapeutic vaccines targeting prostate tumors while delineating prevalent challenges within vaccine research and development. METHODS: We searched electronic databases, including PubMed, Web of Science, Embase, and Scopus, up to August 31, 2024, using keywords such as 'vaccine', 'prostate cancer', 'immunotherapy', and others. We reviewed studies on various therapeutic vaccines, including dendritic cell-based, antigen, nucleic acid, and tumor cell vaccines. RESULTS: Studies consistently showed that therapeutic vaccines, notably DC vaccines, had favorable safety profiles with few adverse effects. These vaccines, with varied antigenic formulations, demonstrated strong clinical outcomes, as indicated by metrics such as PSA response rates (9.5%-58%), extended PSA doubling times (52.9%-89.7%), overall survival durations (17.7-33.8 months), two-year mortality rates (0%-12.5%), biochemical relapse rates (42%-73%), and antigen-specific immune responses (33.3%-71.4% in responsive groups). CONCLUSION: While clinical data for tumor vaccines have illuminated robust evidence of tumoricidal activity, the processes of their formulation and deployment are riddled with complexities. Combining vaccines with other therapies may enhance outcomes, and future research should focus on early interventions and deciphering the immune system's role in oncogenesis.
Asunto(s)
Vacunas contra el Cáncer , Inmunoterapia , Neoplasias de la Próstata , Humanos , Vacunas contra el Cáncer/uso terapéutico , Vacunas contra el Cáncer/inmunología , Masculino , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/terapia , Inmunoterapia/métodos , Células Dendríticas/inmunologíaRESUMEN
Electrochemical reduction of CO2 into high-value-added products is a potential approach to solving environmental problems but is limited by poor product selectivity and low efficiency. Metal-organic framework (MOF) materials have been considered one of the most promising catalysts, but their application is limited by complicated preparation processes, especially during the synthesis of organic ligands. In this work, a new three-dimensional Cu-MOF (JXUST-301) with high porosity was constructed based on the naphthalene diimide (NDI) ligand. Furthermore, JXUST-301 with ligand defects (JXUST-301D) originating from the missing NDI unit was synthesized via an in situ reaction. The presence of ligand defects endows JXUST-301D with a better CO2RR performance with a FEC2 of 56.7% and a jC2 of -162.4 mA cm-2. Mechanistic studies revealed that the hierarchical pore structure and amino sites are created from the absence of the NDI unit, which promotes the exposure of catalytically active sites and CO2 enrichment. Furthermore, the electronic structure of the Cu sites is modulated to upshift the d-band center, facilitating chemical adsorption and activation of key reaction intermediates. This work provides new insight into the in situ preparation of efficient Cu-MOF catalysts by introducing defects for the CO2RR.
RESUMEN
The incorporation of transition-metal single atoms as molecular functional entities into the skeleton of graphdiyne (GDY) to construct novel two-dimensional (2D) metal-acetylide frameworks, known as metalated graphynes (MGYs), is a promising strategy for developing efficient catalysts, which can combine the tunable charge transfer of GDY frameworks, the catalytic activity of metal and the precise distribution of single metallic centers. Herein, four highly conjugated MGY photocatalysts based on NiII, PdII, PtII, and HgII were synthesized for the first time using the 'bottom-up' strategy through the use of M-C bonds (-C≡C-M-C≡C-). Remarkably, the NiII-based graphyne (TEPY-Ni-GY) exhibited the highest CO generation rate of 18.3 mmol g-1 h-1 and a selectivity of 98.8%. This superior performance is attributed to the synergistic effects of pyrenyl and -C≡C-Ni(PBu3)2-C≡C- moieties. The pyrenyl block functions as an intramolecular π-conjugation channel, facilitating kinetically favorable electron transfer, while the -C≡C-Ni(PBu3)2-C≡C- moiety serves as the catalytic site that enhances CO2 adsorption and activation, thereby suppressing competitive hydrogen evolution. This study provides a new perspective on MGY-based photocatalysts for developing highly active and low-cost catalysts for CO2 reduction.
RESUMEN
Urban tree belts reduce noise pollution, but limited research has focused on the mitigation potential of single trees. Identifying individual tree characteristics that influence noise propagation can assist in selecting trees to improve urban soundscapes at multiple scales. This study introduces a methodology to evaluate and predict the sound attenuation of single trees using 3D tree morphology data and sound observations. We extracted structural characteristics for 26 trees on Nanjing University's Xianlin campus from handheld terrestrial LiDAR. Second, the sound attenuation of each sample tree was quantified systematically using a sound source and a receiver. The sound level meter was placed in front of and behind each sample tree to record the received sound levels. The sound source was positioned 1.5m above ground to emit white noise, ensuring the front receiver recording sound levels of 55, 60, and 68 dBA. We established a support vector regression (SVR) with a linear (LN) kernel to predict the sound attenuation of single trees based on their 3D characteristics. Single trees yielded an insertion loss of 2-3 dBA, effectively eliminating sound above 500 Hz and increasing with the frequency. It is also interesting to note that the insertion loss increases with increasing source sound levels. Regression analysis revealed that an increase in crown leaf area index (ß = 0.332, p < 0.01) and average leaf inclination (ß = 0.168, p < 0.01) reduced sound significantly, indicating the tree canopy's predominant role in impeding sound propagation. The SVR-LN model, established using standardized parameters with statistical significance, exhibited strong predictive sound attenuation performance using tree characteristics (R2 = 0.74, RMSE = 0.38, and MSE = 0.15). This study addresses a research gap in the acoustic effects of single trees and provides a framework for accurately evaluating and predicting sound attenuation based on 3D characteristics. The findings can assist urban planners and policymakers in strategically planting trees to foster healthier and quieter living spaces for residents.
RESUMEN
PURPOSE OF REVIEW: This review aims to synthesize the old issues and current understandings of the etiology of liver cancer, focusing on the diverse causative factors influenced by geographical, socioeconomic, and lifestyle variations across different regions. RECENT FINDINGS: We highlight significant geographic disparities in liver cancer risk factors. While hepatitis B and C viruses, aflatoxin exposure, and alcohol consumption remain globally established contributors; metabolic dysfunction-associated steatotic liver disease and metabolic syndromes are increasingly prominent in the West. Chronic HBV and aflatoxin continue to dominate as risk factors in Asia and Africa. Dietary factors, metabolic diseases like diabetes and obesity, genetic predispositions, environmental risk factors and lifestyle choices such as smoking and alcohol use play substantial roles in specific populations. Protective factors like coffee and tea consumption, along with aspirin use, vegetables and fruits have shown potential in reducing HCC risk, although findings vary by population and dietary habits. Liver cancer etiology is influenced by various factors that differ by region. Established risk factors include hepatitis B and C, aflatoxin, and alcohol. Emerging risks, such as metabolic dysfunction-associated steatotic liver disease, are more prevalent in Western countries, while aflatoxin and HBV remains significant in Asia and Africa. Diet, metabolic conditions like diabetes and obesity, genetic predispositions, and lifestyle choices also play crucial roles. Coffee, tea, aspirin, vegetables, and fruits may reduce HCC risk, but effectiveness varies. Future research should integrate epidemiology, genetics, and nutrition, with global cooperation and data sharing essential for effective cancer control strategies.
RESUMEN
BACKGROUND: Mpox has spread to many countries around the world. While the existing live attenuated mpox vaccines are effective, advances in 21st century technologies now enable the development of vaccines with more specific antigens, clearer mechanisms, and more controllable side effects. METHODS: We systematically evaluated the immunogenicity and protective efficacy of the A35R, M1R and B6R antigens of the mpox virus (MPXV). With these findings, we designed three single-chain trivalent mRNA vaccines (AMAB-wt, AMAB-C140S and AMB-C140S) by integrating the soluble regions of these antigens into single mRNA-encoded polypeptides based on their protein structures. Then, the immunogenicity and protective efficacy of these single-chain mRNA vaccines were evaluated in mice models against both VACV and MPXV. FINDINGS: The three single-chain vaccines elicited neutralising antibodies that effectively neutralised both VACV and MPXV. The single-chain vaccines or cocktail vaccine containing mRNAs encoding soluble antigen (sA35R + sM1R + sB6R) exhibited 100% or 80% protection against a lethal dose of VACV challenge, while the cocktail of full-length antigens (A35 + M1 + B6) and the live attenuated vaccine, VACV Tian Tan (VACV-VTT), completely failed to protect mice. Moreover, the single-chain vaccines significantly reduced viral load in the lungs and ovaries of MPXV-challenged mice. INTERPRETATION: Compared with the cocktail vaccines, our single-chain designs demonstrated similar or superior immunogenicity and protective efficacy. Importantly, the simplicity of the single-chain vaccines enhances both the controllability and accessibility of mpox vaccines. We believe these single-chain vaccines qualify as the next-generation mpox vaccines. FUNDING: National Natural Science Foundation of China and Youth Innovation Promotion Association of the CAS.
RESUMEN
A compact, multi-channel ionic liquid-gated graphene field-effect transistor (FET) has been proposed and developed in our work for on-field continuous monitoring of nitrate nitrogen and other nitrogen fertilizers to achieve sustainable and efficient farming practices in agriculture. However, fabricating graphene FETs with easy filling of ionic liquids, minimal graphene defects, and high process yields remains challenging, given the sensitivity of these devices to processing conditions and environmental factors. In this work, two approaches for the fabrication of our graphene FETs were presented, evaluated, and compared for high yields and easy filling of ionic liquids. The process difficulties, major obstacles, and improvements are discussed herein in detail. Both devices, those fabricated using a 3 µm-thick CYTOP® layer for position restriction and volume control of the ionic liquid and those using a ~20 nm-thick photosensitive hydrophobic layer for the same purpose, exhibited typical FET characteristics and were applicable to various application environments. The research findings and experiences presented in this paper will provide important references to related societies for the design, fabrication, and application of liquid-gated graphene FETs.
RESUMEN
This study was first conducted to investigate the effects of acute lead exposure on developing zebrafish embryos or larvae from 24 to 120 h post-fertilization (hpf). Our data showed that treatment with 50-200 µM lead significantly affected larval survivability and morphology compared to the respective control. Second, we chose 120 hpf larvae treated with 12.5 µM lead for RNA sequencing due to its exposure level being sufficient to produce toxic effects with minimum death and lead bioaccumulation in developing zebrafish. A total of 137.45 million raw reads were obtained, and more than 86% of clean data were mapped to the zebrafish reference genome. Differential expression profiles generated 116 up- and 34 down-regulated genes upon lead exposure. The most enriched GO terms for representative DEGs were ion transport and lipid metabolism. Third, a comparison with the dataset of mercury-regulated gene expression identified 94 genes (64 up-regulated and 30 down-regulated) for exposure specific to lead, as well as 422 genes (338 up-regulated and 84 down-regulated) for exposure specific to mercury. In addition, 56 genes were co-regulated by micromolar mercury and lead treatment, and the expression of thirteen genes, including mt2, ctssb.1, prdx1, txn, sqrdl, tmprss13a, socs3a, trpv6, abcb6a, gsr, hbz, fads2, and zgc:92590 were validated by qRT-PCR. These genes were mainly associated with metal ion binding, proteolysis, antioxidant activity, signal transduction, calcium ion or oxygen transport, the fatty acid biosynthetic process, and protein metabolism. Taken together, these findings help better understand the genome-wide responses of developing zebrafish to lead or mercury and provide potential biomarkers for acute exposure to toxic metals.
RESUMEN
BACKGROUND Traditional open surgery for displaced scapular body and neck fractures often results in significant trauma and complications. This study aimed to assess the efficacy of a combined medial and lateral minimally invasive approach compared with the traditional Judet approach. MATERIAL AND METHODS A retrospective analysis was conducted on 36 patients (22 men, 14 women; mean age 45.6 years) with displaced scapular body and neck fractures treated between May 2016 and May 2022. Nineteen patients underwent the minimally invasive approach, while 17 received the traditional Judet approach. Primary outcomes included surgical incision length, intraoperative blood loss, complication rate, time to postoperative pain relief (VAS score ≤3), and Constant-Murley shoulder score at 12 months. Statistical analysis was done using the t test and chi-square test. RESULTS The minimally invasive group had shorter incision lengths (mean difference: 10.0 cm; 95% CI: 8.1-11.9; P<0.001) and lower blood loss (mean difference: 129.4 mL; 95% CI: 119.0-139.8; P<0.001). They also experienced faster pain relief (mean difference: 3.0 days; 95% CI: 2.5-3.5; P<0.001) and higher Constant-Murley scores (mean difference: 7.4 points; 95% CI: 4.9-9.9; P<0.001). There were no significant differences in operative duration or fracture healing time. CONCLUSIONS The combined medial and lateral minimally invasive approach offers superior outcomes in reducing incision length, blood loss, complications, and pain, with enhanced shoulder function, making it a safe and effective alternative to the traditional Judet approach.
Asunto(s)
Fijación Interna de Fracturas , Fracturas Óseas , Procedimientos Quirúrgicos Mínimamente Invasivos , Escápula , Humanos , Masculino , Femenino , Escápula/cirugía , Escápula/lesiones , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Estudios Retrospectivos , Adulto , Fracturas Óseas/cirugía , Fijación Interna de Fracturas/métodos , Resultado del Tratamiento , Dolor PostoperatorioRESUMEN
Jumonji domain-containing protein D3 (JMJD3) is a 2-oxoglutarate-dependent dioxygenase that specifically removes transcriptional repression marks di- and tri-methylated groups from lysine 27 on histone 3 (H3K27me2/3). The erasure of these marks leads to the activation of some associated genes, thereby influencing various biological processes, such as development, differentiation, and immune response. However, comprehensive descriptions regarding the relationship between JMJD3 and inflammation are lacking. Here, we provide a comprehensive overview of JMJD3, including its structure, functions, and involvement in inflammatory pathways. In addition, we summarize the evidence supporting JMJD3's role in several inflammatory diseases, as well as the potential therapeutic applications of JMJD3 inhibitors. Additionally, we also discuss the challenges and opportunities associated with investigating the functions of JMJD3 and developing targeted inhibitors and propose feasible solutions to provide valuable insights into the functional exploration and discovery of potential drugs targeting JMJD3 for inflammatory diseases.
RESUMEN
Anionic nido-carboranes, as open-cage analogues of closo-carboranes with strong hydrophilicity and higher potential in the development of biomedicines, have been notably more challenging because of their strong interaction with transition metals. While the exo-cage B-H activation reactions of nido-carboranes have been widely studied, there are few reports on the direct functionalization of B-H bonds located on a closed polyhedral sphere. Here, we report an efficient palladium-catalyzed regioselective B(2/3)-H alkenylation of nido-carboranes with various alkenes and alkyne coupling partners, enabled by 3-methylpyridine directing groups, to achieve a regiocontrollable functionalization of B(2/3)-H vertices over highly reactive exo-cage B11-H vertex in nido-carboranes.
RESUMEN
Liver cancer causes upwards of 1 million cancer deaths annually and is projected to rise by at least 55% over the next 15 years. Two of the major risk factors contributing to liver cancer have been well documented by multiple epidemiologic studies and the hepatitis B virus (HBV) and aflatoxin show a synergy that increases by more than 8-fold the risk of liver cancer relative to HBV alone. Using the population-based cancer registry established by the Qidong Liver Cancer Institute in 1972 and aflatoxin-specific biomarkers, we document that reduction of aflatoxin exposure has likely contributed to a nearly 70% decline in age-standardized liver cancer incidence over the past 30 years despite an unchanging prevalence of HBV infection in cases. A natural experiment of economic reform in the 1980s drove a rapid switch from consumption of heavily contaminated corn to minimally, if any, contaminated rice and subsequent dietary diversity. Aflatoxin consumption appears to accelerate the time to liver cancer diagnosis; lowering exposure to this carcinogen adds years of life before a cancer diagnosis. Thus, in 1990 the median age of diagnosis was 48 years, while increasing to 67 years by 2021. These findings have important translational public health implications since up to 5 billion people worldwide might be routinely exposed to dietary aflatoxin, especially in societies using corn as the staple food. Interventions against aflatoxin are an achievable outcome leading to a reduction in liver cancer incidence and years of delay of its nearly always fatal diagnosis.
RESUMEN
Stroke, a leading cause of death and disability, often results from ischemic events that cut off the brain blood flow, leading to neuron death. Despite treatment advancements, survivors frequently endure lasting impairments. A key focus is the ischemic penumbra, the area around the stroke that could potentially recover with prompt oxygenation; yet its monitoring is complex. Recent progress in bioluminescence-based oxygen sensing, particularly through the Green enhanced Nano-lantern (GeNL), offers unprecedented views of oxygen fluctuations in vivo. Utilized in awake mice, GeNL has uncovered hypoxic pockets within the cerebral cortex, revealing the brain's oxygen environment as a dynamic landscape influenced by physiological states and behaviors like locomotion and wakefulness. These findings illuminate the complexity of oxygen dynamics and suggest the potential impact of hypoxic pockets on ischemic injury and recovery, challenging existing paradigms and highlighting the importance of microenvironmental oxygen control in stroke resilience. This review examines the implications of these novel findings for stroke research, emphasizing the criticality of understanding pre-existing oxygen dynamics for addressing brain ischemia. The presence of hypoxic pockets in non-stroke conditions indicates a more intricate hypoxic scenario in ischemic brains, suggesting strategies to alleviate hypoxia could lead to more effective treatments and rehabilitation. By bridging gaps in our knowledge, especially concerning microenvironmental changes post-stroke, and leveraging new technologies like GeNL, we can pave the way for therapeutic innovations that significantly enhance outcomes for stroke survivors, promising a future where an understanding of cerebral oxygenation dynamics profoundly informs stroke therapy.
RESUMEN
While certain members of ubiquitin-coupled enzymes (E2s) have garnered attention as potential therapeutic targets across diverse diseases, research progress on Ubiquitin-Conjugating Enzyme 5 (UBC5)-a pivotal member of the E2s family involved in crucial cellular processes such as apoptosis, DNA repair, and signal transduction-has been relatively sluggish. Previous findings suggest that UBC5 plays a vital role in the ubiquitination of various target proteins implicated in diseases and homeostasis, particularly in various cancer types. This review comprehensively introduces the structure and biological functions of UBC5, with a specific focus on its contributions to the onset and advancement of diverse diseases. It suggests that targeting UBC5 holds promise as a therapeutic approach for disease therapy. Recent discoveries highlighting the high homology between UBC5, UBC1, and UBC4 have provided insight into the mechanism of UBC5 in protein degradation and the regulation of cellular functions. As our comprehension of the structural distinctions among UBC5 and its homologues, namely UBC1 and UBC4, advances, our understanding of UBC5's functional significance also expands.
RESUMEN
BACKGROUND: The high sensitivity of HBsAg quantitative tests has led to some challenges in the qualitative interpretation of weakly positive specimens. This study aimed to explore the clinical utility of neutralization confirma-tory testing for specimens with low positive hepatitis B surface antigen (HBsAg). METHODS: A retrospective analysis was conducted on outpatient and inpatient cases, from January 2021 to January 2022, at the Zhongshan City People's Hospital, Zhongshan. Confirmatory testing as well as enzyme-linked immunosorbent assay (ELISA) was applied to reanalyze 382 samples with low positive HBsAg detected by chemilumi-nescence microparticle immunoassay (CMIA). A retrospective analysis of hepatitis B serum markers, including e-antigen, e-antibody, and core antibody patterns, was also performed. RESULTS: When the HBsAg value ranged from 0.05 - 0.09 IU/mL, the positivity rate of the confirmatory testing was 34.5%. The HBsAg true positivity levels were all between 0.07 and 0.09. In the range of 0.10 - 0.49, the positivity rate of confirmatory testing was 96.1%. The three methods exhibited a high consistency, when testing samples with relatively high HBsAg values. A receiver operating characteristic (ROC) analysis showed that the optimal sensitivity and specificity were achieved at 0.14 IU/mL. For the HBV e-antigen-positive and negative groups, the positivity rate of confirmatory testing was 100% and 93.8%, with no statistical difference between them. CONCLUSIONS: For specimens with weakly positive, low-value HBsAg, particularly when the hepatitis B surface an-tigen level is less than 0.14 IU/mL, neutralization confirmatory testing can serve as a means for further confirmation.