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This study aimed to assess the impact of Saccharomyces cerevisiae and different non-Saccharomyces cerevisiae (Zygosaccharomyces bailii, Hanseniaspora opuntiae and Zygosaccharomyces rouxii) on the volatile compounds and sensory properties of low-alcohol pear beverages fermented from three varieties of pear juices (Korla, Laiyang and Binzhou). Results showed that all three pear juices were favorable matrices for yeasts growth. Non-Saccharomyces cerevisiae exhibited a higher capacity for acetate ester production compared to Saccharomyces cerevisiae, resulting in a significant enhancement in sensory complexity of the beverages. PCA and sensory analysis demonstrated that pear varieties exerted a stronger influence on the crucial volatile components and aroma characteristics of the fermented beverages compared to the yeast species. CA results showed different yeast strains exhibited suitability for the fermentation of specific pear juice varieties.

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Fermentación , Odorantes , Pyrus , Saccharomyces cerevisiae , Compuestos Orgánicos Volátiles , Compuestos Orgánicos Volátiles/metabolismo , Compuestos Orgánicos Volátiles/análisis , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/crecimiento & desarrollo , Pyrus/microbiología , Pyrus/química , Odorantes/análisis , Jugos de Frutas y Vegetales/análisis , Jugos de Frutas y Vegetales/microbiología , Gusto , Humanos , Zygosaccharomyces/metabolismo , Zygosaccharomyces/crecimiento & desarrollo , Hanseniaspora/metabolismo , Hanseniaspora/crecimiento & desarrollo , Frutas/microbiología , Frutas/química , Saccharomycetales

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BACKGROUND: Inositol-requiring enzyme 1 (IRE1) is an endoplasmic reticulum (ER)-resident transmembrane protein that senses ER stress and mediates an essential arm of the unfolded protein response (UPR). IRE1 reduces ER stress by upregulating the expression of multiple ER chaperones through activation of X-box-binding protein 1 (XBP1). Emerging lines of evidence have revealed that IRE1-XBP1 axis serves as a multipurpose signal transducer during oncogenic transformation and cancer development. In this study, we explore how IRE1-XBP1 signaling promotes chemoresistance in lung cancer. METHODS: The expression patterns of UPR components and MRP1 were examined by Western blot. qRT-PCR was employed to determine RNA expression. The promoter activity was determined by luciferase reporter assay. Chemoresistant cancer cells were analyzed by viability, apoptosis. CUT & Tag (Cleavage under targets and tagmentation)-qPCR analysis was used for analysis of DNA-protein interaction. RESULTS: Here we show that activation of IRE1α-XBP1 pathway leads to an increase in MDR-related protein 1 (MRP1) expression, which facilitates drug extrusion and confers resistance to cytotoxic chemotherapy. At the molecular level, XBP1-induced c-Myc is necessary for SREBP1 expression, and SREBP1 binds to the MRP1 promoter to directly regulate its transcription. CONCLUSIONS: We conclude that IRE1α-XBP1 had important role in chemoresistance and appears to be a novel prognostic marker for lung cancer.

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Self-assembly of biomolecules provides a powerful tool for a wide range of applications in nanomedicine, biosensing and imaging, vaccines, computation, nanophotonics, etc. The key is to rationally design building blocks and the intermolecule interactions. Along this line, structural DNA nanotechnology has rapidly developed by limiting DNA secondary structures to primarily well-established, B-form DNA duplexes, which can be readily and reliably predicted. As the field evolves, more sophisticated structural elements must be introduced. While increasing the structural complexity, they bring challenges to predicting DNA nanostructures. In the past, a brutal and tedious error-and-trial approach has often been used to solve this problem. Here, we report a case study of applying AlphaFold 3 to model the structural elements to facilitate DNA nanostructure design. This protocol is expected to be generally applicable and greatly facilitates the further development of structural DNA nanotechnology.

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Neovaginas are surgically constructed to correct uterovaginal agenesis in women with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome or as part of gender-affirming surgery for transfeminine individuals. Understanding the assembly of the neovaginal microbiota is crucial for guiding its management. To address this, we conducted a longitudinal study on MRKH patients following laparoscopic peritoneal vaginoplasty. Our findings reveal that the early microbial assemblage exhibited stochastic characteristics, accompanied with a notable bloom of Enterococcus faecalis and genital Mycoplasmas. While both the pre-surgery dimple microbiota and the fecal microbiota constituted the primary species pool, the neovaginal microbiota developed into a microbiota that resembled that of a normal vagina at 6-12 months post-surgery, albeit with a bacterial vaginosis (BV)-like structure. By 2-4 years post-surgery, the neovaginal microbiota had further evolved into a structure closely resembling with the homeostatic pre-surgery dimple microbiota. This concords with the development of the squamous epithelium in the neovagina and highlights the pivotal roles of progressive selective forces imposed by the evolving neovaginal environment and the colonization tropism of vaginal species. Notably, we observed that strains of Lactobacillus crispatus colonizing the neovagina primarily originated from the dimple. Since L. crispatus is generally associated with vaginal health, this finding suggests potential avenues for future research to promote its colonization.

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Trastornos del Desarrollo Sexual 46, XX , Anomalías Congénitas , Microbiota , Conductos Paramesonéfricos , Vagina , Vagina/microbiología , Humanos , Femenino , Trastornos del Desarrollo Sexual 46, XX/microbiología , Trastornos del Desarrollo Sexual 46, XX/cirugía , Conductos Paramesonéfricos/anomalías , Adulto , Anomalías Congénitas/microbiología , Estudios Longitudinales , Adulto Joven , Vaginosis Bacteriana/microbiología , Adolescente , Útero/microbiología , Heces/microbiología , Enterococcus faecalis/aislamiento & purificación , Laparoscopía

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Background: To investigate the correlation between retinal vascular changes and ICA stenosis by measuring retinal vessels using full-width-at-half-maximum (FWHM) and intelligent image recognition. Methods: This research selected patients who were admitted to the Vascular Surgery Department of Quzhou People's Hospital from January 2018 to December 2020 and were preparing for Carotid Artery Stenting (CAS). Participants were divided into two groups: without ICA stenosis (Group 0) and with ICA stenosis (Group 1). A total of 109 cases were included in the study, with 50 cases in Group 1 and 59 cases in Group 0. Vascular images of superior temporal zone B of the retina were obtained by spectral domain optical coherence tomography (SD-OCT). The edges of retinal vessels were identified by FWHM. Each vessel of all subjects was measured three times with the FWHM, and the average value was taken to obtain the retinal arteriolar lumen diameter (RALD), retinal arteriolar outer diameter (RAOD), retinal venular lumen diameter (RVLD), and retinal venular outer diameter (RVOD),Arterial Wall Thickness (AWT),Venular Wall Thickness (VWT)=(RVOD-RVLD)/2,Arteriovenous Ratio (AVR) = RAOD/RVOD. Results: We found that compared to Group 0, Group 1 had smaller RALD (P < 0.001) and RAOD (P < 0.001), and wider RVOD (P < 0.001), with thicker VWT (P < 0.001). When compared with the contralateral eye in Group 1, the ipsilateral eye exhibited even smaller RALD,RAOD and AVR (P < 0.001, P < 0.001, P < 0.001). After CAS, the RALD,RAOD and AVR in Group 1 increased (P < 0.001, P < 0.001, P < 0.001),while the RVLD and RVOD decreased (P < 0.05, P < 0.001). Our research reveals a significant correlation between retinal vascular changes and internal ICA stenosis. Conclusion: Utilizing SD-OCT in conjunction with the FWHM,we achieved a non-invasive, intelligent, stable, and precise acquisition of data pertaining to retinal vessels. These findings underscore a significant correlation between alterations in retinal vascular structure and the presence of ICA stenosis, as demonstrated by our research.

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The vermiform appendix plays an important role in colorectal immunity and the homeostasis of the gut microbiome. We aimed to evaluate the prognostic value of prior appendectomy for patients with colorectal cancer (CRC). This study revealed that prior appendectomy is an independent risk factor for the prognosis of patients with CRC, based on a multicentral CRC cohort. We further demonstrated that appendectomy induced a poor prognosis of CRC through the depletion of M1 macrophage cells in AOM-induced mice, which was confirmed in age-, sex-, and location-matched patients' cohorts and orthotopic model models with the CT26 cell line. Poor responses to anti-PD-1 immunotherapy were detected in patients with CRC with appendectomy, and cetuximab is an effective treatment for patients with appendectomy-associated colorectal cancer (APD-CRC) to improve their prognosis. Our study will provide a reference for developing treatment plans for a considerable number of patients with APD-CRC, which is of great clinical significance.

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Cryptorchidism, commonly known as undescended testis, affects 1%-9% of male newborns, posing infertility and testis tumor risks. Despite its prevalence, the detailed pathophysiology underlying male infertility within cryptorchidism remains unclear. Here, we profile and analyze 46,644 single-cell transcriptomes from individual testicular cells obtained from adult males diagnosed with cryptorchidism and healthy controls. Spermatogenesis compromise in cryptorchidism links primarily to spermatogonium self-renewal and differentiation dysfunctions. We illuminate the involvement of testicular somatic cells, including immune cells, thereby unveiling the activation and degranulation of mast cells in cryptorchidism. Mast cells are identified as contributors to interstitial fibrosis via transforming growth factor ß1 (TGF-ß1) and cathepsin G secretion. Furthermore, significantly increased levels of secretory proteins indicate mast cell activation and testicular fibrosis in the seminal plasma of individuals with cryptorchidism compared to controls. These insights serve as valuable translational references, enriching our comprehension of testicular pathogenesis and informing more precise diagnosis and targeted therapeutic strategies for cryptorchidism.

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PURPOSE: To evaluate the impact of short-term scleral lens (SL) wear on anterior chamber (AC) dimension and central corneal thickness (CCT) in healthy Chinese people. METHODS: This is a prospective, daily wear study. Eligible participants were dispensed SLs to correct refractive errors. Anterior segment (AS) parameters were measured by AS optical coherence tomography (AS-OCT) before, during, and after 2 and 4 hours of lens wear. Repeated-measures analysis of variance (ANOVA) was used to analyze the changes in AS parameters over time. RESULTS: Twelve subjects (10 females and 2 males) with a mean age of 25.3 ± 3.8 years (ranging from 21 to 34 years) were recruited. The AC parameters, including anterior chamber depth (ACD) from the endothelium (endo-ACD), angle opening distance at 500 µm (AOD500), and trabecular-iris space area at 500 µm (TISA500), significantly decreased after wearing SLs for 4 hours (P<0.05). CCT increased by 12 µm (2.29 %) after wearing SLs for 4 hours (P=0.013). CONCLUSION: This study suggests that SL wear has a significant impact on AS dimensions in patients with healthy corneas in the short term with SL in situ, but tend to recover quickly after SL removal. Further research is needed to determine whether the change in AS dimensions during SL wear affects aqueous humor (AH) outflow and causes changes in intraocular pressure (IOP).

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The dataset of cattle biometric features is a pivotal asset for improving livestock management and promoting smart agriculture innovation. We obtained a dataset of images capturing the side and back views of Horqin yellow cattle from a farm in eastern Inner Mongolia, China. These data consist of images of 72 free-range Horqin yellow cattle taken with a mobile camera on the grasslands. Each cattle is accompanied by detailed annotations, including oblique body length, withers height, heart girth, hip length, as well as body weight among other crucial data points. This information is considered as high-quality biological feature data. In the field of computer vision, utilizing this dataset can facilitate the construction of deep learning models to develop an automated livestock monitoring system. The aim is to enhance management efficiency and operational effectiveness within the livestock industry. By integrating biological feature information, specific model tools can be employed for body condition assessment and health monitoring research. This approach enables the effective identification and prevention of disease conditions, ultimately providing a deeper level of care and support for livestock welfare and health. The cattle dataset offers support for smart agriculture by enabling the development of intelligent farm management systems. These systems facilitate real-time alerts for livestock health and environmental monitoring. This advancement will drive the modernization and digitization of animal husbandry, fostering agricultural intelligence and sustainable development.

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BACKGROUND: Preoperative risk stratification is significant for the management of endometrial cancer (EC) patients. Radiomics based on magnetic resonance imaging (MRI) in combination with clinical features may be useful to predict the risk grade of EC. AIM: To construct machine learning models to predict preoperative risk stratification of patients with EC based on radiomics features extracted from MRI. METHODS: The study comprised 112 EC patients. The participants were randomly separated into training and validation groups with a 7:3 ratio. Logistic regression analysis was applied to uncover independent clinical predictors. These predictors were then used to create a clinical nomogram. Extracted radiomics features from the T2-weighted imaging and diffusion weighted imaging sequences of MRI images, the Mann-Whitney U test, Pearson test, and least absolute shrinkage and selection operator analysis were employed to evaluate the relevant radiomic features, which were subsequently utilized to generate a radiomic signature. Seven machine learning strategies were used to construct radiomic models that relied on the screening features. The logistic regression method was used to construct a composite nomogram that incorporated both the radiomic signature and clinical independent risk indicators. RESULTS: Having an accuracy of 0.82 along with an area under the curve (AUC) of 0.915 [95% confidence interval (CI): 0.806-0.986], the random forest method trained on radiomics characteristics performed better than expected. The predictive accuracy of radiomics prediction models surpassed that of both the clinical nomogram (AUC: 0.75, 95%CI: 0.611-0.899) and the combined nomogram (AUC: 0.869, 95%CI: 0.702-0.986) that integrated clinical parameters and radiomic signature. CONCLUSION: The MRI-based radiomics model may be an effective tool for preoperative risk grade prediction in EC patients.

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Human activities led to elevation in carbon dioxide (CO2) concentrations in atmosphere. While such increase per se may be beneficial for the growth of some crops, it comes with a caveat of affecting crop nutritional status. Here, we present a comprehensive analysis of changes in concentration of essential (Cu, Fe, Mn, Zn, Mo, Ni) and non-essential (Ba, Cd, Cr, Hg, Pb, and Sr) heavy metals in response to elevated CO2, drawing on a meta-analysis of 1216 paired observations. The major findings are as follows: (1) Elevated CO2 leads to reduced concentrations of Cu, Fe, Mn, and Zn in crops; (2) the extent of above reduction varies among plants species and is most pronounced in cereals and then in legumes and vegetables; (3) reduction in accumulation of non-essential (toxic) metals is less pronounced, potentially leading to an unfavorable essential/non-essential metal ratio in plants; (4) the above effects will come with significant implication to human health, exacerbating effects of the "hidden hunger" caused by the lack of Fe and Zn in the human diets. The paper also analyses the mechanistic basis of nutrient acquisition (both at physiological and molecular levels) and calls for the changes in the governmental policies to increase efforts of plant breeders to create genotypes with improved nutrient use efficiency for essential micronutrients while uncoupling their transport from non-essential (toxic) heavy metals.

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As emerging and re-emerging pathogens, filoviruses, especially Ebola virus (EBOV), pose a great threat to public health and require sustained attention and ongoing surveillance. More vaccines and antiviral drugs are imperative to be developed and stockpiled to respond to unpredictable outbreaks. Virus-like vesicles, generated by alphavirus replicons expressing homogeneous or heterogeneous glycoproteins (GPs), have demonstrated the capacity of self-propagation and shown great potential in vaccine development. Here, we describe a novel class of EBOV-like vesicles (eVLVs) incorporating both EBOV GP and VP40. The eVLVs exhibited similar antigenicity as EBOV. In murine models, eVLVs were highly attenuated and elicited robust GP-specific antibodies with neutralizing activities. Importantly, a single dose of eVLVs conferred complete protection in a surrogate EBOV lethal mouse model. Furthermore, our VLVs strategy was also successfully applied to Marburg virus (MARV), the representative member of the genus Marburgvirus. Taken together, our findings indicate the feasibility of an alphavirus-derived VLVs strategy in combating infection of filoviruses represented by EBOV and MARV, which provides further evidence of the potential of this platform for universal live-attenuated vaccine development.

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The heavy metal lead (Pb) pollution in marine environment has been widely concerned. The liver and intestine are important for the health of fish. In this study, the grouper were exposed to 1 µg/L Pb for 14 days, and the physiological homeostasis changes were explored via gut-liver axis. The results showed that Pb stress caused liver morphological changes, oxidative stress, and the accumulation and peroxidation of the lipids. The liver metabolism were disturbed, especially amino acid metabolism and the synthesis and degradation of ketone bodies. Pb stress also caused intestinal mucosal ablation, tight junction dysfunction and inflammatory response. Additionally, intestinal microbial diversity was decreased, and the community composition was altered especially several bacteria genera (Ruminococcus UCG-005, Ruminococcus UCG-014, Oscillibacter, and Streptococcus) were significantly correlated with the physiological indexes and metabolites of the liver. These results reveal that Pb stress negatively affect the physiological homeostasis of the grouper via gut-liver axis.

Asunto(s)

Microbioma Gastrointestinal , Homeostasis , Plomo , Hígado , Contaminantes Químicos del Agua , Animales , Plomo/toxicidad , Hígado/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Microbioma Gastrointestinal/efectos de los fármacos , Estrés Oxidativo , Lubina/fisiología

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BACKGROUND: Family with sequence similarity 109, member B (FAM109B) is involved in endocytic transport and affects genetic variation in brain methylation. It is one of the important genes related to immune cell-associated diseases. In the tumor immune system, methylation can regulate tumor immunity and influence the maturation and functional response of immune cells. Whether FAM109B is involved in tumor progression and its correlation with the tumor immune microenvironment has not yet been disclosed. METHODS: A comprehensive pan-cancer analysis of FAM109B expression, prognosis, immunity, and TMB was conducted. The expression, clinical features, and prognostic value of FAM109B in low-grade gliomas (LGG) were evaluated using TCGA, CGGA, and Gravendeel databases. The expression of FAM109B was validated by qRT-PCR, immunohistochemistry (IHC), and Western blotting (WB). The relationship between FAM109B and methylation, Copy Number Variation (CNV), prognosis, immune checkpoints (ICs), and common chemotherapy drug sensitivity in LGG was explored through Cox regression, Kaplan-Meier curves, and Spearman correlation analysis. FAM109B levels and their distribution were studied using the TIMER database and single-cell analysis. The potential role of FAM109B in gliomas was further investigated through in vitro and in vivo experiments. RESULTS: FAM109B was significantly elevated in various tumor types and was associated with poor prognosis. Its expression was related to aggressive progression and poor prognosis in low-grade glioma patients, serving as an independent prognostic marker for LGG. Glioma grade was negatively correlated with FAM109B DNA promoter methylation. Immune infiltration and single-cell analysis showed significant expression of FAM109B in tumor-associated macrophages (TAMs). The expression of FAM109B was closely related to gene mutations, immune checkpoints (ICs), and chemotherapy drugs in LGG. In vitro studies showed increased FAM109B expression in LGG, closely related to cell proliferation. In vivo studies showed that mice in the sh-FAM109B group had slower tumor growth, slower weight loss, and longer survival times. CONCLUSIONS: FAM109B, as a novel prognostic biomarker for low-grade gliomas, exhibits specific overexpression in TAMs and may be a potential therapeutic target for LGG patients.

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Neoplasias Encefálicas , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Glioma , Clasificación del Tumor , Macrófagos Asociados a Tumores , Glioma/genética , Glioma/patología , Glioma/metabolismo , Humanos , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/patología , Macrófagos Asociados a Tumores/inmunología , Metilación de ADN/genética , Animales , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/inmunología , Pronóstico , Carcinogénesis/genética , Carcinogénesis/patología , Variaciones en el Número de Copia de ADN/genética , Microambiente Tumoral , Línea Celular Tumoral , Femenino , Masculino , Ratones Desnudos , Ratones , Estimación de Kaplan-Meier , Bases de Datos Genéticas

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INTRODUCTION: A local microneedle patch loaded with 5-aminolevulinic acid (ALA) was constructed to improve the efficiency of ALA photodynamic treatment of oral leukoplakia, reduce local photosensitivity reactions, and promote the healing of lesions. METHODS: The microneedle patch loaded with ALA was constructed with the hyaluronic acid (HA) solution (ALA-HAMN), and its morphology, strength, mucosal penetration, and biocompatibility were tested. RESULTS: In vivo safety and permeability tests confirmed that ALA-HAMN had good biocompatibility and could penetrate the mucosal barrier and quickly dissolve and release ALA for in situ transdermal administration. The 4-nitroquinoline oxide (NQO) rat model experiment showed that ALA-HAMN can significantly improve photodynamic therapy (PDT) efficiency and has no damage to mucosal tissue compared with the commonly used ALA cotton ball dressing. CONCLUSIONS: The ALA-loaded microneedle patch was successfully constructed for the photodynamic treatment of oral leukoplakia, and the photodynamic efficiency and comfort of oral leukoplakia were improved, which provided an effective delivery mode to improve clinical ALA-PDT treatment of oral leukoplakia (OLK).

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The aim of this study is to investigate novel strategies for reducing adverse reactions caused by erdafitinib through a drug combination based on its pharmacokinetic characteristics. The spectrum and characterizations of drugs that can inhibit the metabolism of erdafitinib are examined both in vitro and in vivo. The efficacy of combination regimens are then evaluated using subcutaneous xenograft tumor models. The results demonstrated that sertraline and duloxetine, out of more than 100 screened drugs, inhibited the metabolism of erdafitinib through mixed and non-competitive inhibition, respectively. This inhibition primarily occurred via the CYP2C9 and CYP2D6 pathways. The primary alleles of CYP2C9 and CYP2D6 not only determine the metabolic characteristics of erdafitinib but also influence the strength of drug-drug interactions. Co-administration of sertraline or duloxetine with erdafitinib in rats and mice resulted in nearly a three-fold increase in the blood exposure of erdafitinib and its major metabolite M6. When sertraline or duloxetine was combined with 1/3 of the erdafitinib dosage, the anti-proliferative and pro-apoptotic effects on SNU-16 xenografts were comparable to those of the original full dose of erdafitinib. However, the combination regimen significantly mitigated hyperphosphatemia, retinal damage, intestinal villus damage, and gut microbiome dysbiosis. This study utilized pharmacokinetic methods to propose a new formulation of erdafitinib combined with sertraline or duloxetine. The findings suggest that this combination has potential for clinical co-administration based on a database analysis, thereby providing a novel strategy for anti-tumor treatment with fibroblast growth factor receptor (FGFR) inhibitors.

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In recent years, ferroptosis has gradually attracted increasing attention because of its important role in tumors. Ferroptosis resistance is an important cause of tumor metastasis, recurrence and drug resistance. Exploring the initiating factors and specific mechanisms of ferroptosis has become a key strategy to block tumor progression and improve drug sensitivity. As the external space in direct contact with tumor cells, the tumor microenvironment has a great impact on the biological function of tumor cells. The relationships between abnormal environmental characteristics (hypoxia, lactic acid accumulation, etc.) in the microenvironment and ferroptosis of tumor cells has not been fully characterized. This review focuses on the characteristics of the tumor microenvironment and summarizes the mechanisms of ferroptosis under different environmental factors, aiming to provide new insights for subsequent targeted therapy. Moreover, considering the presence of anticancer drugs in the microenvironment, we further summarize the mechanisms of ferroptosis to provide new strategies for the sensitization of tumor cells to drugs.

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With the development of brain-computer interface (BCI) technology and its translational application in clinical medicine, BCI medicine has emerged, ushering in profound changes to the practice of medicine, while also bringing forth a series of ethical issues related to BCI medicine. BCI medicine is progressively emerging as a new disciplinary focus, yet to date, there has been limited literature discussing it. Therefore, this paper focuses on BCI medicine, firstly providing an overview of the main potential medical applications of BCI technology. It then defines the discipline, outlines its objectives, methodologies, potential efficacy, and associated translational medical research. Additionally, it discusses the ethics associated with BCI medicine, and introduces the standardized operational procedures for BCI medical applications and the methods for evaluating the efficacy of BCI medical applications. Finally, it anticipates the challenges and future directions of BCI medicine. In the future, BCI medicine may become a new academic discipline or major in higher education. In summary, this article is hoped to provide thoughts and references for the development of the discipline of BCI medicine.

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Interfaces Cerebro-Computador , Interfaces Cerebro-Computador/tendencias , Humanos , Electroencefalografía , Encéfalo/fisiología

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Negative differential resistance (NDR) devices with a low peak-to-valley voltage difference (ΔV) exhibit a high cut off frequency and low power consumption efficiency, which is significant for fabricating high-performance oscillators. However, achieving an ultralow ΔV is challenging. In this work, we report the first construction of an NDR device utilizing a van der Waals heterostructure composed of semimetallic Td-WTe2 and semiconducting 2H-MoS2. Our findings reveal that the narrow energy region of the decreasing density of states (DOS) above the Fermi level of WTe2 acts as a narrow band gap, facilitating type-III band alignment with MoS2 and enabling band-to-band tunneling-based NDR transport. Notably, the NDR device exhibits an ultralow ΔV of approximately 0.01 V, which is at least an order of magnitude lower than previously reported values. This work not only introduces a new approach for NDR device fabrication but also provides new insights into the pivotal role of Td-WTe2 in NDR transport.