Targeting the HSP47-collagen axis inhibits brain metastasis by reversing M2 microglial polarization and restoring anti-tumor immunity.

Brain metastases (BrMs) are the leading cause of death in patients with solid cancers. BrMs exhibit a highly immunosuppressive milieu and poor response to immunotherapies; however, the underlying mechanism remains largely unclear. Here, we show that upregulation of HSP47 in tumor cells drives metastatic colonization and outgrowth in the brain by creating an immunosuppressive microenvironment. HSP47-mediated collagen deposition in the metastatic niche promotes microglial polarization to the M2 phenotype via the α2ß1 integrin/nuclear factor κB pathway, which upregulates the anti-inflammatory cytokines and represses CD8+ T cell anti-tumor responses. Depletion of microglia reverses HSP47-induced inactivation of CD8+ T cells and abolishes BrM. Col003, an inhibitor disrupting HSP47-collagen association restores an anti-tumor immunity and enhances the efficacy of anti-PD-L1 immunotherapy in BrM-bearing mice. Our study supports that HSP47 is a critical determinant of M2 microglial polarization and immunosuppression and that blocking the HSP47-collagen axis represents a promising therapeutic strategy against brain metastatic tumors.

Pt-S bond stabilized DNAzyme nanosensor with thiol-resistance enabling high-fidelity biosensing.

Gold nanoparticles (Au NPs) have been widely utilized in developing DNAzyme-functionalized nanosensors, most of which were engineered by attaching the thiolated DNAzymes to Au NPs via Au-S bonding. However, the Au NP-DNAzyme nanosensors always suffer from signal distortion when applied in complex environment with abundant thiols, which poses challenge for practical applications. Here, we focus on addressing the root cause of the issue and propose to decorate the Au NPs with a thin layer of platinum, thus facilitating the conjugation of DNAzymes through Pt-S bonding, a thiol-resistant cross-linking. The Pt-S bond stabilized DNAzyme nanosensor effectively minimized false positive signals when detecting l-histidine in infant formulas, as compared to the Au-S stabilized counterpart. This innovative strategy holds promise for high-fidelity biosensing, improving the practical applicability of Au NP-based DNAzyme nanosensor.

Prevotella copri promotes vascular calcification via lipopolysaccharide through activation of NF-κB signaling pathway.

Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri (P. copri) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copri and aortic calcification scores. Moreover, oral administration of live P. copri aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo, accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitro and ex vivo experiments consistently demonstrated that P. copri-derived LPS (Pc-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc-LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc-LPS-induced VSMC calcification. Our study clarifies a novel role of P. copri in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc-LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copri and its-derived LPS as potential therapeutic targets for VC in CKD.

Deficiency of leucine-rich repeat kinase 2 aggravates thioacetamide-induced acute liver failure and hepatic encephalopathy in mice.

BACKGROUND: Hepatic encephalopathy (HE) is closely associated with inflammatory responses. However, as a crucial regulator of the immune and inflammatory responses, the role of leucine-rich repeat kinase 2 (LRRK2) in the pathogenesis of HE remains unraveled. Herein, we investigated this issue in thioacetamide (TAA)-induced HE following acute liver failure (ALF). METHODS: TAA-induced HE mouse models of LRRK2 wild type (WT), LRRK2 G2019S mutation (Lrrk2G2019S) and LRRK2 knockout (Lrrk2-/-) were established. A battery of neurobehavioral experiments was conducted. The biochemical indexes and pro-inflammatory cytokines were detected. The prefrontal cortex (PFC), striatum (STR), hippocampus (HIP), and liver were examined by pathology and electron microscopy. The changes of autophagy-lysosomal pathway and activity of critical Rab GTPases were analyzed. RESULTS: The Lrrk2-/--HE model reported a significantly lower survival rate than the other two models (24% vs. 48%, respectively, p < 0.05), with no difference found between the WT-HE and Lrrk2G2019S-HE groups. Compared with the other groups, after the TAA injection, the Lrrk2-/- group displayed a significant increase in ammonium and pro-inflammatory cytokines, aggravated hepatic inflammation/necrosis, decreased autophagy, and abnormal phosphorylation of lysosomal Rab10. All three models reported microglial activation, neuronal loss, disordered vesicle transmission, and damaged myelin structure. The Lrrk2-/--HE mice presented no severer neuronal injury than the other genotypes. CONCLUSIONS: LRRK2 deficiency may exacerbate TAA-induced ALF and HE in mice, in which inflammatory response is evident in the brain and aggravated in the liver. These novel findings indicate a need of sufficient clinical awareness of the adverse effects of LRRK2 inhibitors on the liver.

Differential analysis of serum immunology and gut microbiota in patients with gastrointestinal diseases.

Objective: Gastric and intestinal diseases possess distinct characteristics although they are interconnected. The primary objective of this study was to investigate the pathogenesis of gastrointestinal diseases through different analyses of clinical characteristics, serum immunology, and gut microbiota in patients with gastrointestinal diseases. Methods: We collected serum samples from 89 patients with gastrointestinal diseases and 9 healthy controls for immunological assessment, stool samples for DNA extraction, library construction, sequencing, as well as clinical data for subsequent analysis. Results: Regarding clinical characteristics, there were significant differences between the disease group and the healthy control (HC) group, particularly in terms of age, cancer antigen 125 (CA125), cancer antigen 199 (CA199), alpha-fetoprotein (AFP), total bilirubin (TBIL) and indirect bilirubin (IBIL). The intestinal disease (ID) group exhibited the highest IL-6 level, which significantly differed from the stomach disease (SD) group (p < 0.05). In comparing the HC with the ID groups, significant differences in abundance were detected across 46 species. The HC group displayed a greater abundance of Clostridiales, Clostridia, Firmicutes, Bifidobacterium, Bifidobacteriaceae, Bifidobacteriales, Actinobacteria, Veillonellaceae, Longum, Copri, Megamonas and Callidus than other species. Similarly, when comparing the HC with the SD groups, significant differences in abundance were identified among 49 species, with only one species that the Lachnospiraceae in the HC group exhibited a higher abundance than others. Furthermore, certain clinical characteristics, such as CA125, CA199, glucose (Glu), creatine kinase-MB (CKMB) and interleukin-22 (IL-22), displayed positive correlations with enriched gut species in the ID and SD groups, while exhibiting a negative correlation with the HC group. Conclusion: The disturbance in human gut microbiota is intimately associated with the development and progression of gastrointestinal diseases. Moreover, the gut microbiota in the HC group was found more diverse than that in the ID and SD groups, and there were significant differences in microbial species among the three groups at different classification levels. Notably, a correlation was identified between specific clinical characteristics (e.g., CA125, CA199, Glu, CKMB and IL-22) and gut microbiota among patients with gastrointestinal diseases.

Long-Term Disinfection in Operating Rooms Affects Skin Microbiota and Metabolites of Medical Personnel.

INTRODUCTION: Disinfectants play a critical role in reducing healthcare-associated infections by eliminating microorganisms on surfaces. However, prolonged use of disinfectants may adversely affect the skin microflora, essential for skin health and infection prevention. This study investigates the impact of disinfection on the skin microbiota and metabolites of medical personnel in operating rooms, aiming to provide a scientific foundation for safeguarding their skin health. METHODS: We conducted 16S sequencing and metabolomic analysis to assess the effects of disinfection on the skin microbiota and metabolites of medical personnel. Samples were collected from operating room personnel after disinfectant exposure to identify changes in microbial communities and metabolite profiles. RESULTS: Our analysis revealed that prolonged use of disinfectants led to alterations in skin microbial communities and microbial metabolites. These alterations included the production of harmful metabolites that could potentially promote skin infections and other health issues among medical personnel. CONCLUSION: The findings underscore the importance of minimizing disruptions to skin microbiota and metabolites caused by long-term disinfectant use to preserve the overall health of medical personnel. This study provides valuable insights into the relationship between disinfectant use, skin microbiota, and metabolites, highlighting the necessity for further research in this area.

Association of pre-existing depression and anxiety with Omicron variant infection.

Pre-existing psychiatric disorders were linked to an increased susceptibility to COVID-19 during the initial outbreak of the pandemic, while evidence during Omicron prevalence is lacking. Leveraging data from two prospective cohorts in China, we identified incident Omicron infections between January 2023 and April 2023. Participants with a self-reported history or self-rated symptoms of depression or anxiety before the Omicron pandemic were considered the exposed group, whereas the others were considered unexposed. We employed multivariate logistic regression models to examine the association of pre-existing depression or anxiety with the risk of any or severe Omicron infection indexed by medical interventions or severe symptoms. Further, we stratified the analyses by polygenic risk scores (PRSs) for COVID-19 and repeated the analyses using the UK Biobank data. We included 10,802 individuals from the Chinese cohorts (mean age = 51.1 years, 45.6% male), among whom 7841 (72.6%) were identified as cases of Omicron infection. No association was found between any pre-existing depression or anxiety and the overall risk of Omicron infection (odds ratio [OR] =1.04, 95% confidence interval [CI] 0.95-1.14). However, positive associations were noted for severe Omicron infection, either as infections requiring medical interventions (1.26, 1.02-1.54) or with severe symptoms (≥3: 1.73, 1.51-1.97). We obtained comparable estimates when stratified by COVID-19 PRS level. Additionally, using clustering method, we identified eight distinct symptom patterns and found associations between pre-existing depression or anxiety and the patterns characterized by multiple or complex severe symptoms including cough and taste and smell decline (ORs = 1.42-2.35). The results of the UK Biobank analyses corroborated findings of the Chinese cohorts. In conclusion, pre-existing depression and anxiety was not associated with the risk of Omicron infection overall but an elevated risk of severe Omicron infection, supporting the continued efforts on monitoring and possible early intervention in this high-risk population during Omicron prevalence.

Unveiling the oral-gut connection: chronic apical periodontitis accelerates atherosclerosis via gut microbiota dysbiosis and altered metabolites in apoE-/- Mice on a high-fat diet.

The aim of this study was to explore the impact of chronic apical periodontitis (CAP) on atherosclerosis in apoE-/- mice fed high-fat diet (HFD). This investigation focused on the gut microbiota, metabolites, and intestinal barrier function to uncover potential links between oral health and cardiovascular disease (CVD). In this study, CAP was shown to exacerbate atherosclerosis in HFD-fed apoE-/- mice, as evidenced by the increase in plaque size and volume in the aortic walls observed via Oil Red O staining. 16S rRNA sequencing revealed significant alterations in the gut microbiota, with harmful bacterial species thriving while beneficial species declining. Metabolomic profiling indicated disruptions in lipid metabolism and primary bile acid synthesis, leading to elevated levels of taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), and tauroursodeoxycholic acid (TDCA). These metabolic shifts may contribute to atherosclerosis development. Furthermore, impaired intestinal barrier function, characterized by reduced mucin expression and disrupted tight junction proteins, was observed. The increased intestinal permeability observed was positively correlated with the severity of atherosclerotic lesions, highlighting the importance of the intestinal barrier in cardiovascular health. In conclusion, this research underscores the intricate interplay among oral health, gut microbiota composition, metabolite profiles, and CVD incidence. These findings emphasize the importance of maintaining good oral hygiene as a potential preventive measure against cardiovascular issues, as well as the need for further investigations into the intricate mechanisms linking oral health, gut microbiota, and metabolic pathways in CVD development.

Human neural stem cell secretome relieves endoplasmic reticulum stress-induced apoptosis and improves neuronal functions after traumatic brain injury in a rat model.

Neural stem cell secretome (NSC-S) plays an important role in neuroprotection and recovery. Studies have shown that endoplasmic reticulum stress (ER stress) is involved in the progression of traumatic brain injury (TBI) and is a crucial cause of secondary damage and neuronal death after brain injury. Whether NSC-S is engaged in ER stress and ER stress-mediated neuronal apoptosis post-TBI has not been investigated. In the study, the Feeney SD male rat model was established. The results showed that NSC-S treatment significantly improved the behavior of rats with TBI. In addition, NSC-S relieved ER stress in TBI rats and was observed by transmission electron microscopy and western blot. The specific mechanism was further elucidated that restoration was achieved by alleviating the PERK-eIF2α pathway and thus protecting neurons from apoptosis. Notably, the discovery of calumenin (CALU) in NSC-S by liquid chromatography-tandem mass spectrometry (LC-MS/MS/MS) may be related to the protective effect of NSC-S on ER stress in neurons. Also, the mechanism by which it functions may be related to ubiquitination. In summary, NSC-S improved prognosis and ER stress in TBI rats and might be a promising treatment for relieving TBI.

Measurement of liquid viscosity using quartz crystal microbalance (QCM) based on GA-BP neural network.

Sensor technology plays a pivotal role in various aspects of the petroleum industry. The conventional quartz crystal microbalance (QCM) liquid-phase detection method fails to discern the viscosity and density of solutions separately, rendering it incapable of characterizing the properties of unknown liquid solutions. This presents a formidable challenge to the application of QCM in the petroleum industry. In this study, we aim to assess the feasibility of exclusively utilizing a single QCM sensor for liquid viscosity measurements. Validation experiments were conducted, emphasizing the influence of temperature and solution concentration on the viscosity measurement results. The results indicate that the QCM liquid viscosity response model can achieve viscosity measurements in the temperature range of 20 to 60 °C and concentration range of 10%-95% glycerol solution using a single QCM, with a maximum error of 7.32%. Simultaneously, with the objective of enhancing the model's measurement precision, as an initial investigation, we employed a backpropagation neural network combined with genetic algorithm (to optimize the measurement data. The results demonstrate a substantial improvement in the measurement accuracy of the QCM sensor, with a root mean square error of 3.89 and an absolute error of 3.07% in predicting viscosity values. The purpose of this research was to extend neural networks into the evaluation system of QCM sensors for assessing the viscosity properties of liquid in the oil industry, providing insights into the application of QCM sensors in the petroleum industry for viscosity measurement and improving measurement accuracy.

Electrogenerated Chemiluminescence Biosensor for Quantization of Matrix Metalloproteinase-3 in Serum via Target-Induced Cleavage of Oligopeptide.

A highly sensitive and selective electrogenerated chemiluminescence (ECL) biosensor was developed for the determination of matrix metalloproteinase 3 (MMP-3) in serum via the target-induced cleavage of an oligopeptide. One ECL probe (named as Ir-peptide) was synthesized by covalently linking a new cyclometalated iridium(III) complex ([(3-pba)2Ir(bpy-COOH)](PF6)) (3-pba = 3-(2-pyridyl) benzaldehyde, bpy-COOH = 4'-methyl-2,2'-bipyridine-4-carboxylic acid) with an oligopeptide (CGVPLSLTMGKGGK). An ECL biosensor was fabricated by firstly casting Nafion and gold nanoparticles (AuNPs) on a glassy carbon electrode and then self-assembling both of the ECL probes, 6-mercapto-1-hexanol and zwitterionic peptide, on the electrode surface, from which the AuNPs could be used to amplify the ECL signal and Ir-peptide could serve as an ECL probe to detect the MMP-3. Thanks to the MMP-3-induced cleavage of the oligopeptide contributing to the decrease in ECL intensity and the amplification of the ECL signal using AuNPs, the ECL biosensor could selectively and sensitively quantify MMP-3 in the concentration range of 10-150 ng·mL-1 and with both a limit of quantification (26.7 ng·mL-1) and a limit of detection (8.0 ng·mL-1) via one-step recognition. In addition, the developed ECL biosensor showed good performance in the quantization of MMP-3 in serum samples, with a recovery of 92.6% ± 2.8%-105.6% ± 5.0%. An increased level of MMP-3 was found in the serum of rheumatoid arthritis patients compared with that of healthy people. This work provides a sensitive and selective biosensing method for the detection of MMP-3 in human serum, which is promising in the identification of patients with rheumatoid arthritis.

A-type proanthocyanidins: Sources, structure, bioactivity, processing, nutrition, and potential applications.

A-type proanthocyanidins (PAs) are a subgroup of PAs that differ from B-type PAs by the presence of an ether bond between two consecutive constitutive units. This additional C-O-C bond gives them a more stable and hydrophobic character. They are of increasing interest due to their potential multiple nutritional effects with low toxicity in food processing and supplement development. They have been identified in several plants. However, the role of A-type PAs, especially their complex polymeric form (degree of polymerization and linkage), has not been specifically discussed and explored. Therefore, recent advances in the physicochemical and structural changes of A-type PAs and their functional properties during extraction, processing, and storing are evaluated. In addition, discussions on the sources, structures, bioactivities, potential applications in the food industry, and future research trends of their derivatives are highlighted. Litchis, cranberries, avocados, and persimmons are all favorable plant sources. Α-type PAs contribute directly or indirectly to human nutrition via the regulation of different degrees of polymerization and bonding types. Thermal processing could have a negative impact on the amount and structure of A-type PAs in the food matrix. More attention should be focused on nonthermal technologies that could better preserve their architecture and structure. The diversity and complexity of these compounds, as well as the difficulty in isolating and purifying natural A-type PAs, remain obstacles to their further applications. A-type PAs have received widespread acceptance and attention in the food industry but have not yet achieved their maximum potential for the future of food. Further research and development are therefore needed.

Metabolic Profile and Long-Term Risk of Depression, Anxiety, and Stress-Related Disorders.

Importance: Biomarkers of lipid, apolipoprotein, and carbohydrate metabolism have been previously suggested to be associated with the risk for depression, anxiety, and stress-related disorders, but results are inconsistent. Objective: To examine whether the biomarkers of carbohydrate, lipid, and apolipoprotein metabolism are associated with the risk of depression, anxiety, and stress-related disorders. Design, Setting, and Participants: This population-based cohort study with longitudinal data collection assessed 211 200 participants from the Apolipoprotein-Related Mortality Risk (AMORIS) cohort who underwent occupational health screening between January 1, 1985, and December 31, 1996, mainly in the Stockholm region in Sweden. Statistical analysis was performed during 2022 to 2023. Exposures: Lipid, apolipoprotein, and carbohydrate biomarkers measured in blood. Main Outcomes and Measures: The associations between biomarker levels and the risk of developing depression, anxiety, and stress-related disorders through the end of 2020 were examined using Cox proportional hazards regression models. In addition, nested case-control analyses were conducted within the cohort, including all incident cases of depression, anxiety, and stress-related disorders, and up to 10 control individuals per case who were individually matched to the case by year of birth, sex, and year of enrollment to the AMORIS cohort, using incidence density sampling. Population trajectories were used to illustrate the temporal trends in biomarker levels for cases and controls. Results: A total of 211 200 individuals (mean [SD] age at first biomarker measurement, 42.1 [12.6] years; 122 535 [58.0%] male; 188 895 [89.4%] born in Sweden) participated in the study. During a mean (SD) follow-up of 21.0 (6.7) years, a total of 16 256 individuals were diagnosed with depression, anxiety, or stress-related disorders. High levels of glucose (hazard ratio [HR], 1.30; 95% CI, 1.20-1.41) and triglycerides (HR, 1.15; 95% CI, 1.10-1.20) were associated with an increased subsequent risk of all tested psychiatric disorders, whereas high levels of high-density lipoprotein (HR, 0.88; 95% CI, 0.80-0.97) were associated with a reduced risk. These results were similar for male and female participants as well as for all tested disorders. The nested case-control analyses demonstrated that patients with depression, anxiety, or stress-related disorders had higher levels of glucose, triglycerides, and total cholesterol during the 20 years preceding diagnosis, as well as higher levels of apolipoprotein A-I and apolipoprotein B during the 10 years preceding diagnosis, compared with control participants. Conclusions and Relevance: In this cohort study of more than 200 000 participants, high levels of glucose and triglycerides and low levels of high-density lipoprotein were associated with future risk of depression, anxiety, and stress-related disorders. These findings may support closer follow-up of individuals with metabolic dysregulations for the prevention and diagnosis of psychiatric disorders.

[Baicalin induces ferroptosis in HepG2 cells by inhibiting ROS-mediated PI3K/Akt/FoxO3a signaling pathway].

This study aims to investigate whether baicalin induces ferroptosis in HepG2 cells and decipher the underlying mechanisms based on network pharmacology and cell experiments. HepG2 cells were cultured in vitro and the cell viability was detected by the cell counting kit-8(CCK-8). The transcriptome data of hepatocellular carcinoma were obtained from the Cancer Genome Atlas(TCGA), and the ferroptosis gene data from FerrDb V2. The DEG2 package was used to screen the differentially expressed genes(DEGs), and the common genes between DEGs and ferroptosis genes were selected as the target genes that mediate ferroptosis to regulate hepatocellular carcinoma progression. The functions and structures of the target genes were analyzed by Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment with the thresholds of P<0.05 and |log_2(fold change)|>0.5. DCFH-DA probe was used to detect the changes in the levels of cellular reactive oxygen species(ROS) in each group. The reduced glutathione(GSH) assay kit was used to measure the cellular GSH level, and Fe~(2+) assay kit to determine the Fe~(2+) level. Real-time quantitative PCR(RT-PCR) was employed to measure the mRNA levels of glutathione peroxidase 4(GPX4) and solute carrier family 7 member 11(SLC7A11) in each group. Western blot was employed to determine the protein levels of GPX4, SLC7A11, phosphatidylinositol 3-kinase(PI3K), p-PI3K, protein kinase B(Akt), p-Akt, forkhead box protein O3a(FoxO3a), and p-FoxO3a in each group. The results showed that treatment with 200 µmol·L~(-1) baicalin for 48 h significantly inhibited the viability of HepG2 cells. Ferroptosis in hepatocellular carcinoma could be regulated via the PI3K/Akt signaling pathway. The cell experiments showed that baicalin down-regulated the expression of SLC7A11 and GPX4, lowered the GSH level, and increased ROS accumulation and Fe~(2+) production in HepG2 cells. However, ferrostatin-1, an ferroptosis inhibitor, reduced baicalin-induced ROS accumulation, up-regulated the expression of SLC7A11 and GPX4, elevated the GSH level, and decreased PI3K, Akt, and FoxO3a phosphorylation. In summary, baicalin can induce ferroptosis in HepG2 cells by inhibiting the ROS-mediated PI3K/Akt/FoxO3a pathway.

The DNA damage-independent ATM signalling maintains CBP/DOT1L axis in MLL rearranged acute myeloid leukaemia.

The long-term maintenance of leukaemia stem cells (LSCs) is responsible for the high degree of malignancy in MLL (mixed-lineage leukaemia) rearranged acute myeloid leukaemia (AML). The DNA damage response (DDR) and DOT1L/H3K79me pathways are required to maintain LSCs in MLLr-AML, but little is known about their interplay. This study revealed that the DDR enzyme ATM regulates the maintenance of LSCs in MLLr-AML with a sequential protein-posttranslational-modification manner via CBP-DOT1L. We identified the phosphorylation of CBP by ATM, which confers the stability of CBP by preventing its proteasomal degradation, and characterised the acetylation of DOT1L by CBP, which mediates the high level of H3K79me2 for the expression of leukaemia genes in MLLr-AML. In addition, we revealed that the regulation of CBP-DOT1L axis in MLLr-AML by ATM was independent of DNA damage activation. Our findings provide insight into the signalling pathways involoved in MLLr-AML and broaden the understanding of the role of DDR enzymes beyond processing DNA damage, as well as identigying them as potent cancer targets.

Formation of reactive intermediates in paddy water from different temperature zones for the promotion of abiotic ammonification.

The paddy field is a hot area of biogeochemical process. The paddy water has a large capacity in photo-generation of reactive intermediates (RIs) due to abundant photosensitive dissolved organic matter (DOM), which is influenced by the spatial heterogeneity of paddy soils but rarely been explored. Our work presents the first investigation of the role of soil properties on photochemistry in paddy water. Soil organic matter (SOM), determined by the temperature, was the dominant factor for the photo-generation of RIs in paddy water of main rice producing areas. The RI concentrations generated with abundant SOM from cool regions are 0.05-8.71 times higher than those for the warm regions in China. The humic-like substance and aromatic-like compounds of DOM plays an essential role in RIs generation, which is abundant in paddy soils rich in SOM from Chinese cool regions. In addition, RIs can efficiently accelerate the photo-ammonification of urea and free amino acids by 15.2 %-164 %, leading to 0.13-0.17 mmol/L/d photo-produced ammonium after fertilization, which is preferentially absorbed by rice. The findings of this study will extend our knowledge of the geochemistry of global paddy field ecosystem. The potential role of RIs in nitrogen cycle should be highlighted in the agroecosystem.

Single-Image-Based Deep Learning for Segmentation of Early Esophageal Cancer Lesions.

Accurate segmentation of lesions is crucial for diagnosis and treatment of early esophageal cancer (EEC). However, neither traditional nor deep learning-based methods up to today can meet the clinical requirements, with the mean Dice score - the most important metric in medical image analysis - hardly exceeding 0.75. In this paper, we present a novel deep learning approach for segmenting EEC lesions. Our method stands out for its uniqueness, as it relies solely on a single input image from a patient, forming the so-called "You-Only-Have-One" (YOHO) framework. On one hand, this "one-image-one-network" learning ensures complete patient privacy as it does not use any images from other patients as the training data. On the other hand, it avoids nearly all generalization-related problems since each trained network is applied only to the same input image itself. In particular, we can push the training to "over-fitting" as much as possible to increase the segmentation accuracy. Our technical details include an interaction with clinical doctors to utilize their expertise, a geometry-based data augmentation over a single lesion image to generate the training dataset (the biggest novelty), and an edge-enhanced UNet. We have evaluated YOHO over an EEC dataset collected by ourselves and achieved a mean Dice score of 0.888, which is much higher as compared to the existing deep-learning methods, thus representing a significant advance toward clinical applications. The code and dataset are available at: https://github.com/lhaippp/YOHO.

Bile acids modified by the intestinal microbiota promote colorectal cancer growth by suppressing CD8+ T cell effector functions.

Concentrations of the secondary bile acid, deoxycholic acid (DCA), are aberrantly elevated in colorectal cancer (CRC) patients, but the consequences remain poorly understood. Here, we screened a library of gut microbiota-derived metabolites and identified DCA as a negative regulator for CD8+ T cell effector function. Mechanistically, DCA suppressed CD8+ T cell responses by targeting plasma membrane Ca2+ ATPase (PMCA) to inhibit Ca2+-nuclear factor of activated T cells (NFAT)2 signaling. In CRC patients, CD8+ T cell effector function negatively correlated with both DCA concentration and expression of a bacterial DCA biosynthetic gene. Bacteria harboring DCA biosynthetic genes suppressed CD8+ T cells effector function and promoted tumor growth in mice. This effect was abolished by disrupting bile acid metabolism via bile acid chelation, genetic ablation of bacterial DCA biosynthetic pathway, or specific bacteriophage. Our study demonstrated causation between microbial DCA metabolism and anti-tumor CD8+ T cell response in CRC, suggesting potential directions for anti-tumor therapy.

Surveillance of tick-borne bacteria infection in ticks and forestry populations in Inner Mongolia, China.

Ticks are one of the most important vectors that can transmit pathogens to animals and human beings. This study investigated the dominant tick-borne bacteria carried by ticks and tick-borne infections in forestry populations in Arxan, Inner Mongolia, China. Ticks were collected by flagging from May 2020 to May 2021, and blood samples were collected from individuals at high risk of acquiring tick-borne diseases from March 2022 to August 2023. The pooled DNA samples of ticks were analyzed to reveal the presence of tick-borne bacteria using high-throughput sequencing of the 16S rDNA V3-V4 region, and species-specific polymerase chain reaction (PCR) related to sequencing was performed to confirm the presence of pathogenic bacteria in individual ticks and human blood samples. All sera samples were examined for anti-SFGR using ELISA and anti-B. burgdorferi using IFA and WB. A total of 295 ticks (282 Ixodes persulcatus and 13 Dermacentor silvarum) and 245 human blood samples were collected. Rickettsia, Anaplasma, Borrelia miyamotoi, and Coxiella endosymbiont were identified in I. persulcatus by high-throughput sequencing, while Candidatus R. tarasevichiae (89.00%, 89/100), B. garinii (17.00%, 17/100), B. afzelii (7.00%, 7/100), and B. miyamotoi (7.00%, 7/100) were detected in I. persulcatus, as well the dual co-infection with Candidatus R. tarasevichiae and B. garinii were detected in 13.00% (13/100) of I. persulcatus. Of the 245 individuals, B. garinii (4.90%, 12/245), R. slovaca (0.82%, 2/245), and C. burnetii (0.41%, 1/245) were detected by PCR, and the sequences of the target genes of B. garinii detected in humans were identical to those detected in I. persulcatus. The seroprevalence of anti-SFGR and anti-B. burgdorferi was 5.71% and 13.47%, respectively. This study demonstrated that Candidatus R. tarasevichiae and B. garinii were the dominant tick-borne bacteria in I. persulcatus from Arxan, and that dual co-infection with Candidatus R. tarasevichiae and B. garinii was frequent. This is the first time that B. miyamotoi has been identified in ticks from Arxan and R. solvaca has been detected in humans from Inner Mongolia. More importantly, this study demonstrated the transmission of B. garinii from ticks to humans in Arxan, suggesting that long-term monitoring of tick-borne pathogens in ticks and humans is important for the prevention and control of tick-borne diseases.

Numerical analysis of on-chip acousto-optic modulators for visible wavelengths.

On-chip acousto-optic modulators that operate at an optical wavelength of 780 nm and a microwave frequency of 6.835 GHz are proposed. The modulators are based on a lithium-niobate-on-sapphire platform and efficiently excite surface acoustic waves and exhibit strong interactions with tightly confined optical modes in waveguides. In particular, a high-efficiency phase modulator and single-sideband mode converter are designed. We found that for both microwave and optical wavelengths below 1 µm, the interactions at the cross-sections of photonic waveguides are sensitive to the waveguide width and are significantly different from those in previous studies. Our designed devices have small footprints and high efficiencies, making them suitable for controlling rubidium atoms and realizing hybrid photonic-atomic chips. Furthermore, our devices have the potential to extend the acousto-optic modulators to other visible wavelengths for other atom transitions and for visible light applications, including imaging and sensing.