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L-type amino acid transporter 1 (LAT1) is upregulated in various cancers and contributes to the growth and proliferation of cancer cells. Previous clinicopathological studies have revealed associations between the high expression of LAT1 and the poor prognosis in multiple cancer types. However, in those studies, the expression of LAT1 has been evaluated solely by immunohistochemistry on resected tumors or tissue biopsies. Cancer cell-derived exosomes are attracting increasing attention as a resource of diagnostic, prognostic, and therapeutic biomarkers. In this study, we revealed the expression of LAT1 on exosomes from pancreatic cancer T3M-4 cells by western blotting, immunoprecipitation, and immuno-transmission electron microscopy. LAT1 was generally detected by western blotting and ELISA on exosomes from several pancreatic, biliary tract, and ovarian cancer cells. Notably, similar trends existed between the abundance of exosomal LAT1 and the cellular LAT1 expression levels. The expression of LAT1 on exosomes in vivo was verified using the peritoneal wash from intraperitoneal T3M-4 tumor-bearing mice. These results indicate that exosomal LAT1 released from cancer cells holds significant potential as a novel biomarker for diagnosis and prognosis.

Background Visceral adiposity index (VAI) and lipid accumulation product (LAP) are comprehensive indicators to evaluate visceral fat and determine the metabolic health of individuals. Carotenoids are a group of naturally occurring antioxidants associated with several diseases. The purpose of this investigation was to explore the association between serum carotenoid concentration and VAI or LAP. Methods The data were obtained from the National Health and Nutrition Examination Survey between 2001 and 2006. The levels of serum carotenoids were evaluated using high-performance liquid chromatography. Multivariate linear regression models were employed to investigate the relationship between levels of serum carotenoids and VAI or LAP. The potential non-linear relationship was determined using threshold effect analysis and fitted smoothing curves. Stratification analysis was performed to investigate the potential modifying factors. Results In total, 5,084 participants were included in this population-based investigation. In the multivariate linear regressions, compared to the lowest quartiles of serum carotenoids, the highest quartiles were significantly associated with VAI, and the effect size (β) and 95% CI was − 0.98 (− 1.34, − 0.62) for α-carotene, − 1.39 (− 1.77, − 1.00) for β-carotene, − 0.79 (− 1.18, − 0.41) for β-cryptoxanthin, − 0.68 (− 0.96, − 0.39) for lutein/zeaxanthin, and − 0.88 (− 1.50, − 0.27) for trans-lycopene. Using piece-wise linear regression models, non-linear relationships were found between β­carotene and trans-lycopene and VAI with an inflection point of 2.44 (log2-transformed, ug/dL) and 3.80 (log2-transformed, ug/dL), respectively. The results indicated that α-carotene, β-cryptoxanthin, and lutein/zeaxanthin were linearly associated with VAI. An inverse association was also found between serum carotenoids and LAP after complete adjustments. Conclusion This study revealed that several serum carotenoids were associated with VAI or LAP among the general American population. Further large prospective investigations are warranted to support this finding.

BackgroundAlbuminuria is a critical prognostic indicator for adverse outcomes (eg, chronic kidney disease, cardiovascular events) in adults with hypertension. While healthy dietary patterns are linked to improved renal and cardiovascular health, the association between overall healthy eating (assessed by a comprehensive index) and albuminuria in this population remains insufficiently investigated.ObjectiveThis study aimed to explore the association between the Healthy Eating Index 2015 (HEI-2015) and albuminuria in US adults with hypertension using National Health and Nutrition Examination Survey (NHANES) 2007–2020 data.MethodsThis was a cross-sectional analysis of data from the NHANES 2007–2020. Participants aged ≥20 years with hypertension defined in accordance with the American Heart Association (AHA) clinical guidelines were included. HEI-2015 score was evaluated from dietary intake data collected by conducting 24-hour dietary recall interviews. Albuminuria was defined as a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g. Logistic regression and restricted cubic spline analysis were used to evaluate the association between HEI-2015 and albuminuria.ResultsA total of 12 829 US adults with hypertension were included, with 2163 (16.86%) having albuminuria. The weighted mean HEI-2015 score was 53.9, and the weighted mean UACR was 60.6 mg/g. In the fully adjusted logistic regression model (model 3), compared with Q1 (reference), the OR of albuminuria for Q4 was 0.75 (95% CI 0.59 to 0.95, p=0.02). For each 13-point increase in HEI-2015, the OR of albuminuria was 0.91 (95% CI 0.83 to 0.99, p=0.04) in model 3. Restricted cubic spline analysis showed a linear association between HEI-2015 and albuminuria (P for non-linearity=0.239, P overall <0.001). Stratified analyses (by age, sex, race, body mass index, etc) showed no significant interaction (all P for interaction >0.05).ConclusionHigher HEI-2015 scores (indicating healthier dietary patterns) are significantly associated with a lower prevalence of albuminuria in US adults with hypertension. These findings support healthy eating as a potential strategy for preventing albuminuria in hypertensive populations.

Recreational use of ketamine (KET) has been increasing worldwide. Previous studies have demonstrated that KET induced neurotoxicity; however, few studies have examined how alcohol (ALC) affects KET-induced neurotoxicity. In light of the fact that some KET abusers combine KET with ALC, the present study was aimed to investigate the effects of ALC on KET-induced neurotoxicity and the underlying mechanism in vitro . Our data revealed that co-treatment with ALC and KET was more detrimental to cell viability than KET single treatment in both PC12 cells and primary cultured rat cortical neurons. Furthermore, ALC exacerbated KET-induced apoptosis characterized by morphological changes and the sub-G1 phase increase, which were mitigated by the pretreatment of CNQX, a known alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainite (KA) receptor antagonist. In addition, ALC and KET co-treatment led to intracellular Ca 2+ overload, down-regulation of p-Akt, p-CREB, PKA, CaMK-IV, Bcl-2 and BDNF expression and up-regulation of cleaved caspase-3 and Bax expression, which can be attenuated by CNQX pretreatment. These results indicate that the potentiation of ALC on KET-induced neurotoxicity was related to the down-regulation of CREB-related pathways. Our present study also indicates that ALC and KET co-abuse might cause serious neurotoxicity which should be conveyed to the public and drew enough attention.

Bone has a special structure that is both stiff and elastic, and the composition of bone confers it with an exceptional mechanical property. However, bone substitute materials that are made of the same hydroxyapatite (HA) and collagen do not offer the same mechanical properties. It is important for bionic bone preparation to understand the structure of bone and the mineralization process and factors. In this paper, the research on the mineralization of collagen is reviewed in terms of the mechanical properties in recent years. Firstly, the structure and mechanical properties of bone are analyzed, and the differences of bone in different parts are described. Then, different scaffolds for bone repair are suggested considering bone repair sites. Mineralized collagen seems to be a better option for new composite scaffolds. Last, the paper introduces the most common method to prepare mineralized collagen and summarizes the factors influencing collagen mineralization and methods to analyze its mechanical properties. In conclusion, mineralized collagen is thought to be an ideal bone substitute material because it promotes faster development. Among the factors that promote collagen mineralization, more attention should be given to the mechanical loading factors of bone.

Stimulus-responsive drug delivery systems generally aim to release the active pharmaceutical ingredient (API) in response to specific conditions and have recently been explored for disease treatments. These approaches can also be extended to molecular imaging to report on disease diagnosis and management. The stimuli used for activation are based on differences between the environment of the diseased or targeted sites, and normal tissues. Endogenous stimuli include pH, redox reactions, enzymatic activity, temperature and others. Exogenous site-specific stimuli include the use of magnetic fields, light, ultrasound and others. These endogenous or exogenous stimuli lead to structural changes or cleavage of the cargo carrier, leading to release of the API. A wide variety of stimulus-responsive systems have been developed—responsive to both a single stimulus or multiple stimuli—and represent a theranostic tool for disease treatment. In this review, stimuli commonly used in the development of theranostic nanoplatforms are enumerated. An emphasis on chemical structure and property relationships is provided, aiming to focus on insights for the design of stimulus-responsive delivery systems. Several examples of theranostic applications of these stimulus-responsive nanomedicines are discussed.

Chemotherapy resistance represents a formidable obstacle in oncological therapeutics, substantially compromising the efficacy of adjuvant chemotherapy regimens and contributing to unfavorable clinical prognoses. Emerging evidence has elucidated the pivotal involvement of exosomes in the dissemination of chemoresistance phenotypes among tumor cells and within the tumor microenvironment. This review delineates two distinct intra-tumoral resistance mechanisms orchestrated by exosomes: (1) the exosome-mediated sequestration of chemotherapeutic agents coupled with enhanced drug efflux in neoplastic cells, and (2) the horizontal transfer of chemoresistance to drug-sensitive cells through the delivery of bioactive molecular cargo, thereby facilitating the propagation of resistance phenotypes across the tumor population. Furthermore, the review covers current in vivo experimental data focusing on targeted interventions against specific genetic elements and exosomal secretion pathways, demonstrating their potential in mitigating chemotherapy resistance. Additionally, the therapeutic potential of inhibiting exosome-mediated transporter transfer strategy is particularly examined as a promising strategy to overcome tumor resistance mechanisms.

Cyanobacteria blooms are a global aquatic environment problem. In recent years, due to global warming and water eutrophication, the surface cyanobacteria accumulate in a certain area to form cyanobacteria blooms driven by wind. Cyanobacteria blooms change the physical and chemical properties of water and cause pollution. Moreover, cyanobacteria release organic matter, N (nitrogen) and P (phosphorus) into the water during their apoptosis, accelerating the eutrophication of the water, threatening aquatic flora and fauna, and affecting the community structure and abundance of microorganisms in the water. Simultaneously, toxins and carcinogens released from cyanobacteria can be enriched through the food chain/web, endangering human health. This study summarized and analyzed the research of the influence of cyanobacteria blooms on the aquatic environment and human health, which is helpful to understand further the harm of cyanobacteria blooms and provide some reference for a related research of cyanobacteria blooms.

An unprecedented soil moisture drought broke out over the Yangtze River basin (YRB) in the summer of 2022 and lasted until the spring of 2023, caused great economic losses and serious environmental issues. With the rapid onset and long-lasting duration, the mega soil drought challenges the current seasonal prediction capacity. Whether the state-of-the-art climate models provide skillful predictions of the onset, persistence and recovery of the 2022–23 mega soil drought needs to be assessed. Identified by the drought area percentage, here we show that the mega soil drought over the YRB started from July, 2022, reached the peak in August, and diminished in April, 2023. Combined with real-time predictions of monthly precipitation released by three climate models participating in the North American multi-model ensemble (NMME) project, we predict the monthly evolution of the 2022–23 soil drought through a joint distribution between precipitation and soil moisture established by the copula method. The results indicate that the NMME/copula prediction well reproduced the spatiotemporal evolution of the mega soil drought at 1 month lead. Using the climatological prediction that relies on the information of initial soil moisture conditions as the reference forecast, the Brier skill score (BSS) values for NMME multi-model ensemble are 0.26, 0.23 and 0.2 for the forecast lead times increased from 1 to 3 months during the entire soil drought period. Specifically, the BSS is 0.14 at 2 months lead during drought onset stage, and 0.26 at 3 months lead during persistence stage, while it is close to zero at all leads during the recovery stage. Our study implies that climate models have great potential in probabilistic seasonal prediction of the onset and persistency of mega soil drought through combining with the copula method.

The prevalence of coronary artery disease (CAD) in Tibetan Highlanders is lower than that in plain-living individuals, but the mechanism still unclear. Gut microbiota (GM) disorder is considered one of the potential factors involved in the pathogenesis of CAD, but the GM characteristics of Tibetan Highlanders suffering from CAD are unknown. We sequenced the V3-V4 region of the 16S ribosomal RNA of gut bacteria from fecal samples from Tibetan and Han CAD patients and healthy individuals inhabiting the Qinghai-Tibet Plateau, as well as from Han CAD patients and healthy individuals living at sea level, and we analyzed the GM characteristics of these subjects by bioinformatics analysis. The results showed that Tibetan Highlanders suffering from CAD had higher GM α-diversity, with differently distributed cluster compared with healthy Tibetan Highlanders and Han CAD patients living at high and low altitudes. Genera Catenibacterium, Clostridium_sensu_stricto , Holdemanella , and Ruminococcus 2 were enriched in Tibetan Highlanders suffering from CAD compared with healthy Tibetan Highlanders and Han CAD patients living at high- and low-altitudes. Prevotella was enriched in Tibetan Highlanders suffering from CAD compared with Han CAD patients living at high- and low-altitudes. Moreover, Catenibacterium was positively correlated with Prevotella . Additionally, Catenibacterium, Holdemanella , and Prevotella were positively correlated with fermented dairy product, carbohydrate and fiber intake by the subjects, while Clostridium_sensu_stricto was negatively correlated with protein intake by the subjects. In conclusion, our study indicated that Tibetan Highlanders suffering from CAD showed distinct GM, which was linked to their unique dietary characteristics and might associated with CAD.