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Purpose: Refractive errors, particularly myopia, constitute a significant global public health concern, contributing to morbidity and disability. A more comprehensive understanding of the determinants of refractive errors and the differences between urban and rural areas is essential to develop effective preventive measures for youth. This study aimed to compare the prevalence and risk factors of refractive errors among youth in urban and rural Tianjin, China. Methods: This school-based cross-sectional study was conducted in 2022. Elementary, middle, and high school students aged 6-18 years from both urban and rural areas of Tianjin were included. All participants underwent visual acuity testing and refractive measurement and completed comprehensive questionnaires. Results: A total of 346,146 participants (176,628 boys) were included in this investigation (50.36% for urban and 49.64% for rural, respectively). Myopia, hyperopia, astigmatism, and anisometropia were present in 56.8, 9.7, 56.64, and 21.3% of urban students, respectively. Similarly, rural students had a prevalence of 57.6, 11.5, 56.48, and 22.0% for the respective conditions. Compared to rural students, after adjusting for age, sex, and other significant variables, urban students were 1.05 times more likely to have myopia (95% CI: 1.03-1.07, p < 0.0001), 0.71 times less likely to have hyperopia (95% CI: 0.69-0.73, p < 0.0001), and 1.02 times more likely to have astigmatism (95% CI: 0.69-0.73, p < 0.0001). There was no significant association between anisometropia and residence (OR: 1.00, 95% CI: 0.98-1.02, p = 0.9850). Sociodemographic and physiological factors contribute to the disparities in the prevalence of refractive errors between urban and rural areas. Age, increased near-work activities, and Decreased outdoor time were identified as risk factors for myopia, astigmatism, and anisometropia. Conversely, the absence of a parental history of refractive errors emerged as a protective factor for myopia and astigmatism among students. Lower parental education levels were negatively correlated with the risk of myopia and anisometropia in their children. Specifically, the lower the parental education, the greater the risk of myopia in their offspring. For urban students only, lower parental education was associated with an increased risk of astigmatism. Conclusion: Crude prevalence estimates May not accurately reflect the true burden of refractive error due to confounding factors such as age and sex. Accounting for these factors revealed that urban students were more likely to have myopia and astigmatism but less likely to have hyperopia compared to their rural counterparts. These disparities highlight the importance of considering geographical variations when implementing strategies for myopia control and prevention.

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The visual search for product packaging involves intricate cognitive processes that are prominently impacted by learned associations derived from extensive long-term experiences. The present research employed EEG technology and manipulated the color display of reference pictures on beverage bottles to explore the underlying neurocognitive pathways. Specifically, we aimed to investigate the influence of color-flavor association strength on the visual processing of such stimuli as well as the in-depth neural mechanisms. The behavioral results revealed that stimuli with strong association strength triggered the fastest response and the highest accuracy, compared with the stimuli with weak association strength and the achromatic ones. The EEG findings further substantiated that the chromatic stimuli evoked a more pronounced N2 component than achromatic ones, and the stimuli with strong association strength elicited larger P3 and smaller N400 amplitudes than the ones with weak association strength. Additionally, the source localization using sLORETA showed significant activations in the inferior temporal gyrus. In conclusion, our research suggests that (1) color expectations would guide visual search process and trigger faster responses to congruent visual stimuli, (2) both the initial perceptual representation and subsequent semantic representation play pivotal roles in effective visual search for the targets, and (3) the color-flavor association strength potentially exerts an impact on visual processing by modulating memory accessibility.

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Zearalenone (ZEN) is a toxic secondary metabolite produced by the Fusarium fungi, which widely contaminates grains, food, and feed, causing health hazards for humans and animals. Therefore, it is essential to find effective ZEN detoxification methods. Enzymatic degradation of ZEN is believed to be an eco-friendly detoxification strategy, specifically thermostable ZEN degradation enzymes are needed in the food and feed industry. In this study, a novel ZEN lactone hydrolase ZHRnZ from Rosellinia necatrix was discovered using bioinformatic and molecular docking technology. The recombinant ZHRnZ showed the best activity at pH 9.0 and 45 °C with more than 90% degradation for ZEN, α-zearalenol (α-ZOL), ß-zearalenol (ß-ZOL) and α-zearalanol (α-ZAL) after incubation for 15 min. We obtained 10 mutants with improved thermostability by single point mutation technology. Among them, mutants E122Q and E122R showed the best performance, which retained more than 30% of their initial activity at 50 °C for 2 min, and approximately 10% of their initial activity at 60 °C for 1 min. The enzymatic kinetic study showed that the catalytic efficiency of E122R was 1.3 times higher than that of the wild-type (WT). Comprehensive consideration suggests that mutant E122R is a promising hydrolase to detoxify ZEN in food and feed.

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Roasted-rice leachate fermentation, a distinctive local tobacco fermentation method in Sichuan, imparts a mellow flavor and glossy texture to tobacco leaves, along with a roasted rice aroma. In order to find out the impact of roasted-rice leachate on cigar tobacco leaves, the physicochemical properties, volatile flavor profile, and microbial community were investigated. The content of protein significantly decreased after fermentation. The volatile flavor compounds increased following roasted-rice leachate fermentation, including aldehydes, alcohols, acids, and esters. High-throughput sequencing identified Staphylococcus, Pseudomonas, Pantoea, Oceanobacillus, Delftia, Corynebacterium, Sphingomonas, Aspergillus, Weissella, and Debaryomyces as the primary genera. Network and correlation analysis showed Debaryomyces played a crucial role in roasted-rice leachate fermentation, due to its numerous connections with other microbes and positive relationships with linoelaidic acid, aromandendrene, and benzaldehyde. This study is useful for gaining insight into the relationship between flavor compounds and microorganisms and provides references regarding the effect of extra nutrients on traditional fermentation products. KEY POINTS: • Volatile flavor compounds increased following roasted-rice leachate fermentation • Staphylococcus was the primary genera in fermented cigar • Debaryomyces may improve the quality of tobacco leaves.

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In orchestrating cell signaling, facilitating plasma membrane repair, supervising protein secretion, managing waste elimination, and regulating energy consumption, lysosomes are indispensable guardians that play a crucial role in preserving intracellular homeostasis. Neurons are terminally differentiated post-mitotic cells. Neuronal function and waste elimination depend on normal lysosomal function. Converging data suggest that lysosomal dysfunction is a critical event in the etiology of Parkinson's disease (PD). Mutations in Glucosylceramidase Beta 1 (GBA1) and leucine-rich repeat kinase 2 (LRRK2) confer an increased risk for the development of parkinsonism. Furthermore, lysosomal dysfunction has been observed in the affected neurons of sporadic PD (sPD) patients. Given that lysosomal hydrolases actively contribute to the breakdown of impaired organelles and misfolded proteins, any compromise in lysosomal integrity could incite abnormal accumulation of proteins, including α-synuclein, the major component of Lewy bodies in PD. Clinical observations have shown that lysosomal protein levels in cerebrospinal fluid may serve as potential biomarkers for PD diagnosis and as signs of lysosomal dysfunction. In this review, we summarize the current evidence regarding lysosomal dysfunction in PD and discuss the intimate relationship between lysosomal dysfunction and pathological α-synuclein. In addition, we discuss therapeutic strategies that target lysosomes to treat PD.

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Pancreatic ductal adenocarcinoma (PDAC) has limited treatment options, emphasizing the urgent need for effective therapies. The predominant driver in PDAC is mutated KRAS proto-oncogene, KRA, present in 90% of patients. The emergence of direct KRAS inhibitors presents a promising avenue for treatment, particularly those targeting the KRASG12C mutated allele, which show encouraging results in clinical trials. However, the development of resistance necessitates exploring potent combination therapies. Our objective was to identify effective KRASG12C-inhibitor combination therapies through unbiased drug screening. Results revealed synergistic effects with son of sevenless homolog 1 (SOS1) inhibitors, tyrosine-protein phosphatase non-receptor type 11 (PTPN11)/Src homology region 2 domain-containing phosphatase-2 (SHP2) inhibitors, and broad-spectrum multi-kinase inhibitors. Validation in a novel and unique KRASG12C-mutated patient-derived organoid model confirmed the described hits from the screening experiment. Our findings propose strategies to enhance KRASG12C-inhibitor efficacy, guiding clinical trial design and molecular tumor boards.

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Microbially induced calcium carbonate precipitation (MICP) provides a novel approach for use in addressing the instabilities of borehole walls comprising broken formations, but the highly alkaline environments of drilling fluids are unfavorable for microbial growth. Therefore, this study investigated the alkali-resistant domestication of Bacillus pasteurii commonly used in MICP. Using gradient domestication, B. pasteurii was domesticated under different pH conditions (pH 8.0, 9.0, 10.0, and 11.0) in sodium carboxymethyl cellulose solid-free drilling fluids. Its growth patterns and variations in urease activity were analyzed to assess the effectiveness of domestication. The Gompertz and logistic models were used to fit the growth patterns of B. pasteurii under different pH conditions, and growth kinetic models were constructed based on the mean square error, Akaike information criterion, and coefficient of determination. The bacterial concentration and urease activity of B. pasteurii were enhanced after alkali-resistant gradient domestication. The Gompertz model accurately described the growth patterns of B. pasteurii after gradient domestication at pH 8.0, 10.0, and 11.0, whereas the logistic model accurately described the growth pattern after gradient domestication at pH 9.0. This study provides scientific evidence and a theoretical basis for the use of B. pasteurii in maintaining the stabilities of borehole walls comprising broken formations.

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Single-ion conductive polymer electrolytes can improve the safety of lithium ion batteries (LIBs) by increasing the lithium transference number (tLi+) and avoiding the growth of lithium dendrites. Meanwhile, the self-assembled ordered structure of liquid crystal polymer networks (LCNs) can provide specific channels for the ordered transport of Li ions. Herein, single-ion conductive nematic and cholesteric LCN electrolyte membranes (denoted as NLCN-Li and CLCN-Li) were successfully prepared. NLCN-Li was then coated on commercial Celgard 2325 while CLCN-Li was coated on poly(vinylidene fluoride-hexafluoropropylene) film, coupled with plasticizer, to make NLCN-Li/Cel and CLCN-Li/Pv quasi-solid-state electrolyte membranes, respectively. Their electrochemical properties were evaluated, and it was found that they possessed benign thermal stability and electrolyte/electrode compatibility, high tLi+ up to 0.98 and high electrochemical stability window up to 5.2 V. A small amount (0.5M) of extra Li salt added to the plasticizer could improve the ion conductivity from 1.79 × 10-5 to 5.04 × 10-4 S cm-1, while the tLi+ remained 0.85. The assembled LFP|Li batteries also exhibited excellent cycling and rate performances. The orderliness of the LCN layer played an important role in the distribution and movement of Li ions, thereby affecting the Li deposition and growth of Li dendrites. As the first report of nematic and cholesteric LCN single-ion conductors, this work sheds light on the design and fabrication of ordered quasi-solid-state electrolytes for high-performance and safe LIBs.

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Hexavalent chromium (Cr(VI)) causes testicular damage and reduces testosterone secretion. Testosterone synthesis relies on cholesterol as a raw material, and its availability can be affected by lipophagy. However, the role of lipophagy in Cr(VI)-induced testicular damage and reduced testosterone secretion remains unclear. In this study, we investigated the effect of Cr(VI) on lipid metabolism and lipophagy in the testes of ICR mice. Forty mice were randomly divided into four groups and exposed to different doses of Cr(VI) (0, 75, 100, 125 mg/kg) for thirty days. Cr(VI) increased the rate of sperm abnormalities, decreased testosterone level, and decreased the levels of testosterone synthesis-related proteins, namely steroidogenic acute regulatory (StAR) and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) proteins. Through metabolomic analysis, Oil Red O staining, and biochemical indicator (triglyceride and total cholesterol) analysis, Cr(VI) was found to disrupt testicular lipid metabolism. Further investigation revealed that Cr(VI) inhibited the AMP-activated protein kinase (AMPK)/sterol regulatory element-binding protein 1 (SREBP1) pathway, elevated levels of the autophagy-related proteins microtubule-associated protein 1 light chain 3B (LC3B) and sequestosome 1 (SQSTM1)/P62 and lipophagy-related proteins Rab7 and Rab10, while increasing colocalization of LC3B and Perilipin2. These findings suggest that Cr(VI) exposure leads to abnormal lipid metabolism in the testes by suppressing the AMPK/SREBP1 pathway and disrupting lipophagy, ultimately reducing testosterone level and inducing testicular damage.

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BACKGROUND: Impaired hypoglycaemic counterregulation has emerged as a critical concern for diabetic patients who may be hesitant to medically lower their blood glucose levels due to the fear of potential hypoglycaemic reactions. However, the patho-genesis of hypoglycaemic counterregulation is still unclear. Glucagon-like peptide-1 (GLP-1) and its analogues have been used as adjunctive therapies for type 1 diabetes mellitus (T1DM). The role of GLP-1 in counterregulatory dys-function during hypoglycaemia in patients with T1DM has not been reported. AIM: To explore the impact of intestinal GLP-1 on impaired hypoglycaemic counterregulation in type 1 diabetic mice. METHODS: T1DM was induced in C57BL/6J mice using streptozotocin, followed by intraperitoneal insulin injections to create T1DM models with either a single episode of hypoglycaemia or recurrent episodes of hypoglycaemia (DH5). Immunofluorescence, Western blot, and enzyme-linked immunosorbent assay were employed to evaluate the influence of intestinal GLP-1 on the sympathetic-adrenal reflex and glucagon (GCG) secretion. The GLP-1 receptor agonist GLP-1(7-36) or the antagonist exendin (9-39) were infused into the terminal ileum or injected intraperitoneally to further investigate the role of intestinal GLP-1 in hypoglycaemic counterregulation in the model mice. RESULTS: The expression levels of intestinal GLP-1 and its receptor (GLP-1R) were significantly increased in DH5 mice. Consecutive instances of excess of intestinal GLP-1 weakens the sympathetic-adrenal reflex, leading to dysfunction of adrenal counterregulation during hypoglycaemia. DH5 mice showed increased pancreatic δ-cell mass, cAMP levels in δ cells, and plasma somatostatin concentrations, while cAMP levels in pancreatic α cells and plasma GCG levels decreased. Furthermore, GLP-1R expression in islet cells and plasma active GLP-1 levels were significantly increased in the DH5 group. Further experiments involving terminal ileal infusion and intraperitoneal injection in the model mice demonstrated that intestinal GLP-1 during recurrent hypoglycaemia hindered the secretion of the counterregulatory hormone GCG via the endocrine pathway. CONCLUSION: Excessive intestinal GLP-1 is strongly associated with impaired counterregulatory responses to hypoglycaemia, leading to reduced appetite and compromised secretion of adrenaline, noradrenaline, and GCG during hypo-glycaemia.

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BACKGROUND: Enshi Yulu tea (ESYL) is the most representative of steamed green tea in China, but its aroma formation in processing is unclear. Thus, the ESYL volatiles during the whole industrial processing were investigated using headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry. RESULTS: A total of 134 volatiles were identified. Among these, 31 differential volatiles [P < 0.05 and variable importance in projection (VIP) > 1] and 25 key volatiles [relative odor activity value (rOAV) and/or the ratio of each rOAV to the maximum rOAV (ROAV) > 1.0] were screened out, wherein ß-ionone and nonanal were the most key odorants. Besides, the sensory evaluation combined with multivariate statistical analysis of volatiles pinpointed spreading, fixation, first drying, and second drying as the key processing steps that have a pronounced influence on the aroma quality of ESYL. Furthermore, the oxidative degradation of unsaturated fatty acids, synthesis of monoterpenes, and degradation of carotenoids were the main metabolic pathway for the formation of key odorants. CONCLUSION: The study provides comprehensive insights into the volatile characteristics during the industrial processing of ESYL and promote our understanding of the aroma formation in steamed green teas. © 2024 Society of Chemical Industry.

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Individuals are apt to link various characteristics of an object or event through different sensory experiences. We conducted two electrophysiological experiments to investigate the effects of color-flavor congruency and association strength on visual search efficiency and the in-depth cognitive mechanisms underlying multisensory processes. Participants were prompted with a flavor label and asked to identify the primed flavor from four beverage bottle images. Experiment 1 focused on color-flavor congruency and noted faster searches for congruent targets than incongruent ones. EEG data exhibited smaller N2, larger P3 and LPC, and increased parietal-occipital midline (POM) alpha power for incongruent targets than congruent ones. Experiment 2 manipulated color-flavor association strength within each flavor. Behavioral findings showed that searches for targets with weak association strength took longer than those with strong association strength. Moreover, time-frequency analysis displayed that the former evoked greater frontal midline (FM) theta power and higher alpha power than the latter. Altogether, our research indicated that (1) color expectations based on prior experience can automatically guide people's attentional selection, (2) the color-flavor congruency and association strength impact the visual search efficiency via distinct pathways, and (3) theta and alpha activities make a pivotal role in unraveling multisensory information processing. These findings shed some light on the intricate cognitive processes involved in crossmodal visual search and the underlying neurocognitive dynamics.

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Thirteen previously undescribed lindenane sesquiterpenoid dimers (LSDs), named chlorahololides G-S (1-13), were isolated from the whole plants of Chloranthus holostegius var. shimianensis, along with ten known analogues (14-23). The structures and absolute configurations of compounds 1-13 were elucidated through comprehensive spectroscopic analysis, NMR and electronic circular dichroism (ECD) calculations, and X-ray single-crystal diffraction. Chlorahololide G (1) represents the first instance of LSDs formed via a C-15-C-9' carbon-carbon single bond, whose plausible biosynthetic pathway was also proposed. Chlorahololides I and J (3 and 4) were deduced to be rare 8,9-seco and 9-deoxy LSDs with C-11-C-7' carbon-carbon bond, respectively. The inhibitory activity against NLRP3 inflammasome activation was evaluated for all isolates, with six compounds (5, 7, 8, 17, 22, and 23) exhibiting significant effects, and IC50 values ranging from 2.99 to 8.73 µM. Additionally, a preliminary structure-activity relationship analysis regarding their inhibition of NLRP3 inflammasome activation was summarized. Compound 17 exhibited dose-dependent inhibition of nigericin-induced pyroptosis in J774A.1 cells. Molecular docking studies suggested a strong interaction between compound 17 and NLRP3.

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Eleven undescribed monoterpenoid bisindole alkaloids, alstomaphyines A-K (1-11), along with three known analogues were isolated from the leaves and stem bark of the Alstonia macrophylla. Compounds 1-3 were unprecedented dimerization alkaloids incorporating a macroline-type motif with an ajmaline-type motif via a C-C linkage. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) calculation, and CD exciton chirality method. Compounds 1-3 displayed potential inhibitory bioactivity against AChE with IC50 values of 4.44 ± 0.35, 3.59 ± 0.18, and 3.71 ± 0.23 µM, respectively. Enzyme kinetic study revealed compounds 1-3 as mixed competitive AChE inhibitors. Besides, compounds 8 and 12-14 exhibited better cytotoxicity against human cancer cell line HT-29 than cisplatin. Flow cytometry data revealed that compounds 8, 13, and 14 significantly induced the HT-29 cells arrest in G0/G1 phase in a concentration-dependent manner.

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Compromised osteogenesis and angiogenesis is the character of stem cell senescence, which brought difficulties for bone defects repairing in senescent microenvironment. As the most abundant bone-related miRNA, miRNA-21-5p plays a crucial role in inducing osteogenic and angiogenic differentiation. However, highly efficient miR-21-5p delivery still confronts challenges including poor cellular uptake and easy degradation. Herein, TDN-miR-21-5p nanocomplex is constructed based on DNA tetrahedral (TDN) and has great potential in promoting osteogenesis and alleviating senescence of senescent bone marrow stem cells (O-BMSCs), simultaneously enhancing angiogenic capacity of senescent endothelial progenitor cells (O-EPCs). Of note, the activation of AKT and Erk signaling pathway may direct regulatory mechanism of TDN-miR-21-5p mediated osteogenesis and senescence of O-BMSCs. Also, TDN-miR-21-5p can indirectly mediate osteogenesis and senescence of O-BMSCs through pro-angiogenic growth factors secreted from O-EPCs. In addition, gelatin methacryloyl (GelMA) hydrogels are mixed with TDN and TDN-miR-21-5p to fabricate delivery scaffolds. TDN-miR-21-5p@GelMA scaffold exhibits greater bone repair with increased expression of osteogenic- and angiogenic-related markers in senescent critical-size cranial defects in vivo. Collectively, TDN-miR-21-5p can alleviate senescence and induce osteogenesis and angiogenesis in senescent microenvironment, which provides a novel candidate strategy for senescent bone repair and widen clinical application of TDNs-based gene therapy.

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A W-doped Pt modified graphene oxide (Pt-W-GO) electrochemical microelectrode was developed to detect hydrogen peroxide (H2O2) in real time at a subcellular scale. Interestingly, results showed that the concentration of H2O2 in the nucleus of HeLa cells was 2.68 times and 0.51 times that in the extracellular membrane and cytoplasm, respectively.

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Membranous nephropathy (MN), an autoimmune disease, can manifest at any age and is among the most common causes of nephrotic syndrome in adults. In 80% of cases, the specific etiology of MN remains unknown, while the remaining cases are linked to drug use or underlying conditions like systemic lupus erythematosus, hepatitis B virus, or malignancy. Although about one-third of patients may achieve spontaneous complete or partial remission with conservative management, another third face an elevated risk of disease progression, potentially leading to end-stage renal disease within 10 years. The identification of phospholipase A2 receptor as the primary target antigen in MN has brought about a significant shift in disease management and monitoring. This review explores recent advancements in the pathophysiology of MN, encompassing pathogenesis, clinical presentations, diagnostic criteria, treatment options, and prognosis, with a focus on emerging developments in pathogenesis and therapeutic strategies aimed at halting disease progression. By synthesizing the latest research findings and clinical insights, this review seeks to contribute to the ongoing efforts to enhance our understanding and management of this challenging autoimmune disorder.

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Glioma is characterized by strong immunosuppression and excessive angiogenesis. Based on existing reports, it can be speculated that the resistance to anti-angiogenic drug vascular endothelial growth factor A (VEGFA) antibody correlates to the induction of novel immune checkpoint indoleamine 2,3-dioxygenase 1 (IDO1), while IDO1 has also been suggested to be related to tumor angiogenesis. Herein, we aim to clarify the potential role of IDO1 in glioma angiogenesis and the mechanism behind it. Bioinformatic analyses showed that the expressions of IDO1 and angiogenesis markers VEGFA and CD34 were positively correlated and increased with pathological grade in glioma. IDO1-overexpression-derived-tryptophan depletion activated the general control nonderepressible 2 (GCN2) pathway and upregulated VEGFA in glioma cells. The tube formation ability of angiogenesis model cells could be inhibited by IDO1 inhibitors and influenced by the activity and expression of IDO1 in condition medium. A significant increase in serum VEGFA concentration and tumor CD34 expression was observed in IDO1-overexpressing GL261 subcutaneous glioma-bearing mice. IDO1 inhibitor RY103 showed positive anti-tumor efficacy, including the anti-angiogenesis effect and upregulation of natural killer cells in GL261 glioma-bearing mice. As expected, the combination of RY103 and anti-angiogenesis agent sunitinib was proved to be a better therapeutic strategy than either monotherapy.

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Blood microbiome signatures in patients with type 1 diabetes (T1D) remain unclear. We profile blood microbiome using 16S rRNA gene sequencing in 77 controls and 64 children with new-onset T1D, and compared it with the gut and oral microbiomes. The blood microbiome of patients with T1D is characterized by increased diversity and perturbed microbial features, with a significant increase in potentially pathogenic bacteria compared with controls. Thirty-six representative genera of blood microbiome were identified by random forest analysis, providing strong discriminatory power for T1D with an AUC of 0.82. PICRUSt analysis suggested that bacteria capable of inducing inflammation were more likely to enter the bloodstream in T1D. The overlap of the gut and oral microbiome with the blood microbiome implied potential translocation of bacteria from the gut and oral cavity to the bloodstream. Our study raised the necessity of further mechanistic investigations into the roles of blood microbiome in T1D.