Changes in the type 2 diabetes gut mycobiome associate with metformin treatment across populations.

The human gut teems with a diverse ecosystem of microbes, yet non-bacterial portions of that community are overlooked in studies of metabolic diseases firmly linked to gut bacteria. Type 2 diabetes mellitus (T2D) is associated with compositional shifts in the gut bacterial microbiome and the mycobiome, the fungal portion of the microbiome. However, whether T2D and/or metformin treatment underpins fungal community changes is unresolved. To differentiate these effects, we curated a gut mycobiome cohort spanning 1,000 human samples across five countries and validated our findings in a murine experimental model. We use Bayesian multinomial logistic normal models to show that T2D and metformin both associate with shifts in the relative abundance of distinct gut fungi. T2D is associated with shifts in the Saccharomycetes and Sordariomycetes fungal classes, while the genera Fusarium and Tetrapisipora most consistently associate with metformin treatment. We confirmed the impact of metformin on individual gut fungi by administering metformin to healthy mice. Thus, metformin and T2D account for subtle, but significant and distinct variation in the gut mycobiome across human populations. This work highlights for the first time that metformin can confound associations of gut fungi with T2D and warrants the need to consider pharmaceutical interventions in investigations of linkages between metabolic diseases and gut microbial inhabitants. IMPORTANCE: This is the largest to-date multi-country cohort characterizing the human gut mycobiome, and the first to investigate potential perturbations in gut fungi from oral pharmaceutical treatment. We demonstrate the reproducible effects of metformin treatment on the human and murine gut mycobiome and highlight a need to consider metformin as a confounding factor in investigations between type 2 diabetes mellitus and the gut microbial ecosystem.

Prevalence of sarcopenic obesity in the older non-hospitalized population: a systematic review and meta-analysis.

BACKGROUND: Sarcopenic obesity emerges as a risk factor for adverse clinical outcomes in non-hospitalized older adults, including physical disabilities, metabolic diseases, and even mortality. In this systematic review and meta-analysis, we investigated the overall SO prevalence in non-hospitalized adults aged ≥ 65 years and assessed the sociodemographic, clinicobiological, and lifestyle factors related to SO. METHODS: We searched the PubMed, Embase, Cochrane Library, and Web of Science databases for studies reporting the prevalence of SO from database inception to October 2023. Two researchers independently screened the literature, evaluated the study quality, and extracted the data. Both fixed- and random-effects models were used in the meta-analysis to estimate the pooled SO prevalence and perform subgroup analyses. Publication and sensitivity bias analyses were performed to test the robustness of the associations. RESULTS: Among 46 studies eligible for review and a total of 71,757 non-hospitalized older adults, the combined prevalence of SO was 14% (95% CI:11-17%, I2 = 99.5%, P < 0.01). Subgroup analysis according to lifestyle factors demonstrated that the SO prevalence was 17% (95% CI: 8-29%, I2 = 99.5%, P < 0.01) in older adults without exercise habits. Regarding clinicobiological factors, older adults with a history of falls (15% [95% CI: 10-22%, I2 = 82%, P < 0.01]), two or more chronic diseases (19% [95% CI: 10-29%, I2 = 97%, P < 0.01]), functional impairment (33% [95% CI: 29-37%, I2 = 0%, P = 0.95]), cognitive impairment (35% [95% CI: 9-65%, I2 = 83%, P = 0.02]), osteoporosis (20% [95% CI: 8-35%, I2 = 96%, P < 0.01]), high fasting glucose level (17% [95% CI: 1-49%, I2 = 98%, P < 0.01]), or the use of antipsychotics (13% [95% CI: 2-28%, I2 = 0%, P = 0.32]) exhibited a higher SO prevalence. CONCLUSION: SO prevalence is high among non-hospitalized older adults, especially those with functional and cognitive impairments. Thus, SO is a potential problem for the aging population; implementation of planned interventions in the community is needed to reduce the prevalence and adverse outcomes of SO.

PERP May Affect the Prognosis of Lung Adenocarcinoma by Inhibiting Apoptosis.

Background: PERP, a member of the peripheral myelin protein gene family, is a new therapeutic target in cancer. The relationships between PERP and immune cell infiltration in lung cancer have not been studied. Therefore, the role of PERP in the tumour microenvironment (TME) of lung cancer needs to be further explored. Methods: In this study, we explored the association between PERP expression and clinical characteristics by analysing data from the TCGA database. Cox regression and Kaplan‒Meier methods were used to investigate the relationship between the expression of PERP and overall survival in patients with lung adenocarcinoma (LUAD). The relationship between PERP expression and the degree of infiltration of specific immune cell subsets in LUAD was evaluated using the TIMER database and GEPIA. We also performed GO enrichment analysis and KEGG enrichment analysis to reveal genes coexpressed with PERP using the Coexpedia database. Finally, we verified the expression and function of PERP in LUAD tissues and the A549 cell line by RT‒PCR, Western blot, CCK-8, IHC, and wound healing assays. The mouse model was used to study the in vivo effects of PERP. Results: According to our results, PERP expression was significantly higher in LUAD tissues and associated with the clinical characteristics of the disease. Survival was independently associated with PERP in LUAD patients. We further verified that PERP might regulate B-cell infiltration in LUAD to affect the prognosis of LUAD. To identify PERP-related signalling pathways in LUAD, we performed a genome-aggregation analysis (GSEA) between low and high PERP expression datasets. LUAD cells express higher levels of PERP than paracarcinoma cells, and PERP inhibits the proliferation and metastasis of A549 cells through apoptosis. Conclusion: PERP may affect the prognosis of lung adenocarcinoma by inhibiting apoptosis and is associated with immune cell infiltration.

Pan-transcriptomic analysis reveals alternative splicing control of cold tolerance in rice.

Plants have evolved complex mechanisms to adapt to harsh environmental conditions. Rice (Oryza sativa) is a staple food crop that is sensitive to low temperatures. However, its cold stress responses remain poorly understood, thus limiting possibilities for crop engineering to achieve greater cold tolerance. In this study, we constructed a rice pan-transcriptome and characterized its transcriptional regulatory landscape in response to cold stress. We performed Iso-Seq and RNA-Seq of 11 rice cultivars subjected to a time-course cold treatment. Our analyses revealed that alternative splicing-regulated gene expression plays a significant role in the cold stress response. Moreover, we identified CATALASE C (OsCATC) and Os03g0701200 as candidate genes for engineering enhanced cold tolerance. Importantly, we uncovered central roles for the 2 serine-arginine-rich proteins OsRS33 and OsRS2Z38 in cold tolerance. Our analysis of cold tolerance and resequencing data from a diverse collection of 165 rice cultivars suggested that OsRS2Z38 may be a key selection gene in japonica domestication for cold adaptation, associated with the adaptive evolution of rice. This study systematically investigated the distribution, dynamic changes, and regulatory mechanisms of alternative splicing in rice under cold stress. Overall, our work generates a rich resource with broad implications for understanding the genetic basis of cold response mechanisms in plants.

[Role and mechanism of macrophage-mediated osteoimmune in osteonecrosis of the femoral head].

Objective: To summarize the research progress on the role of macrophage-mediated osteoimmune in osteonecrosis of the femoral head (ONFH) and its mechanisms. Methods: Recent studies on the role and mechanism of macrophage-mediated osteoimmune in ONFH at home and abroad were extensively reviewed. The classification and function of macrophages were summarized, the osteoimmune regulation of macrophages on chronic inflammation in ONFH was summarized, and the pathophysiological mechanism of osteonecrosis was expounded from the perspective of osteoimmune, which provided new ideas for the treatment of ONFH. Results: Macrophages are important immune cells involved in inflammatory response, which can differentiate into classically activated type (M1) and alternatively activated type (M2), and play specific functions to participate in and regulate the physiological and pathological processes of the body. Studies have shown that bone immune imbalance mediated by macrophages can cause local chronic inflammation and lead to the occurrence and development of ONFH. Therefore, regulating macrophage polarization is a potential ONFH treatment strategy. In chronic inflammatory microenvironment, inhibiting macrophage polarization to M1 can promote local inflammatory dissipation and effectively delay the progression of ONFH; regulating macrophage polarization to M2 can build a local osteoimmune microenvironment conducive to bone repair, which is helpful to necrotic tissue regeneration and repair to a certain extent. Conclusion: At present, it has been confirmed that macrophage-mediated chronic inflammatory immune microenvironment is an important mechanism for the occurrence and development of ONFH. It is necessary to study the subtypes of immune cells in ONFH, the interaction between immune cells and macrophages, and the interaction between various immune cells and macrophages, which is beneficial to the development of potential therapeutic methods for ONFH.

Multiomics analysis reveals the genetic and metabolic characteristics associated with the low prevalence of dental caries.

Background: Despite poor oral hygiene, the Baiku Yao (BKY) ethnic group in China presents a low prevalence of dental caries, which may be related to genetic susceptibility. Due to strict intra-ethnic marriage rule, this ethnic has an advantage in studying the interaction between genetic factors and other regulatory factors related to dental caries. Methods: Peripheral blood from a caries-free adult male was used for whole genome sequencing, and the BKY assembled genome was compared to the Han Chinese genome. Oral saliva samples were collected from 51 subjects for metabolomic and metagenomic analysis. Multiomics data were integrated for combined analysis using bioinformatics approaches. Results: Comparative genomic analysis revealed the presence of structural variations in several genes associated with dental caries. Metabolomic and metagenomic sequencing demonstrated the caries-free group had significantly higher concentration of antimicrobials and higher abundance of core oral health-related microbiota. The functional analysis indicated that cationic antimicrobial peptide resistance and the lipopolysaccharide biosynthesis pathway were enriched in the caries-free group. Conclusions: Our study provided new insights into the specific regulatory mechanisms that contribute to the low prevalence of dental caries in the specific population and may provide new evidence for the genetic diagnosis and control of dental caries.

Telomere-to-telomere assembly of cassava genome reveals the evolution of cassava and divergence of allelic expression.

Cassava is a crucial crop that makes a significant contribution to ensuring human food security. However, high-quality telomere-to-telomere cassava genomes have not been available up to now, which has restricted the progress of haploid molecular breeding for cassava. In this study, we constructed two nearly complete haploid resolved genomes and an integrated, telomere-to-telomere gap-free reference genome of an excellent cassava variety, 'Xinxuan 048', thereby providing a new high-quality genomic resource. Furthermore, the evolutionary history of several species within the Euphorbiaceae family was revealed. Through comparative analysis of haploid genomes, it was found that two haploid genomes had extensive differences in linear structure, transcriptome features, and epigenetic characteristics. Genes located within the highly divergent regions and differentially expressed alleles are enriched in the functions of auxin response and the starch synthesis pathway. The high heterozygosity of cassava 'Xinxuan 048' leads to rapid trait segregation in the first selfed generation. This study provides a theoretical basis and genomic resource for molecular breeding of cassava haploids.

The multi-kingdom microbiome of the goat gastrointestinal tract.

BACKGROUND: Goat is an important livestock worldwide, which plays an indispensable role in human life by providing meat, milk, fiber, and pelts. Despite recent significant advances in microbiome studies, a comprehensive survey on the goat microbiomes covering gastrointestinal tract (GIT) sites, developmental stages, feeding styles, and geographical factors is still unavailable. Here, we surveyed its multi-kingdom microbial communities using 497 samples from ten sites along the goat GIT. RESULTS: We reconstructed a goat multi-kingdom microbiome catalog (GMMC) including 4004 bacterial, 71 archaeal, and 7204 viral genomes and annotated over 4,817,256 non-redundant protein-coding genes. We revealed patterns of feeding-driven microbial community dynamics along the goat GIT sites which were likely associated with gastrointestinal food digestion and absorption capabilities and disease risks, and identified an abundance of large intestine-enriched genera involved in plant fiber digestion. We quantified the effects of various factors affecting the distribution and abundance of methane-producing microbes including the GIT site, age, feeding style, and geography, and identified 68 virulent viruses targeting the methane producers via a comprehensive virus-bacterium/archaea interaction network. CONCLUSIONS: Together, our GMMC catalog provides functional insights of the goat GIT microbiota through microbiome-host interactions and paves the way to microbial interventions for better goat and eco-environmental qualities. Video Abstract.

State-dependent alterations of implicit emotional dominance during binocular rivalry in subthreshold depression.

Binocular rivalry, a visual perception phenomenon where two or more percepts alternate every few seconds when distinct stimuli are presented to the two eyes, has been reported as a biomarker in several psychiatric disorders. It is unclear whether abnormalities of binocular rivalry in depression could occur when emotional rivaling stimuli are used, and if so, whether an emotional binocular rivalry test could provide a trait-dependent or state-dependent biomarker. In the current study, 34 individuals with subthreshold depression and 31 non-depressed individuals performed a binocular rivalry task associated with implicit emotional processing. Participants were required to report their perceived orientations of the rival gratings in the foreground and to neglect emotional face stimuli in the background. The participants were retested after an approximately 4-month time interval. Compared to the non-depressed group, the subthreshold depression group showed significantly longer perceptual dominance durations of the grating with emotional faces as the background (i.e., implicit emotional dominance) at the initial assessment. However, the abnormality was not found at the follow-up assessment. More importantly, we found smaller changes in depressive severity at the follow-up assessment for individuals displaying longer emotional dominance at the initial assessment than for individuals with weaker emotional dominance. The current emotional binocular rivalry test may provide an objective, state-dependent biomarker for distinguishing individuals with subthreshold depression from non-depressed individuals.

Novel insights of EZH2-mediated epigenetic modifications in degenerative musculoskeletal diseases.

Degenerative musculoskeletal diseases (Osteoporosis, Osteoarthritis, Degenerative Spinal Disease and Sarcopenia) are pathological conditions that affect the function and pain of tissues such as bone, cartilage, and muscles, and are closely associated with ageing and long-term degeneration. Enhancer of zeste homolog 2 (EZH2), an important epigenetic regulator, regulates gene expression mainly through the PRC2-dependent trimethylation of histone H3 at lysine 27 (H3K27me3). Increasing evidence suggests that EZH2 is involved in several biological processes closely related to degenerative musculoskeletal diseases, such as osteogenic-adipogenic differentiation of bone marrow mesenchymal stem cells, osteoclast activation, chondrocyte functional status, and satellite cell proliferation and differentiation, mainly through epigenetic regulation (H3K27me3). Therefore, the synthesis and elucidation of the role of EZH2 in degenerative musculoskeletal diseases have attracted increasing attention. In addition, although EZH2 inhibitors have been approved for clinical use, whether they can be repurposed for the treatment of degenerative musculoskeletal diseases needs to be considered. Here, we reviewed the role of EZH2 in the development of degenerative musculoskeletal diseases and brought forward prospects of its pharmacological inhibitors in the improvement of the treatment of the diseases.

Changes in the Type 2 diabetes gut mycobiome associate with metformin treatment across populations.

The human gut teems with a diverse ecosystem of microbes, yet non-bacterial portions of that community are overlooked in studies of metabolic diseases firmly linked to gut bacteria. Type 2 diabetes mellitus (T2D) associates with compositional shifts in the gut bacterial microbiome and fungal mycobiome, but whether T2D and/or pharmaceutical treatments underpin the community change is unresolved. To differentiate these effects, we curated a gut mycobiome cohort to-date spanning 1,000 human samples across 5 countries and a murine experimental model. We use Bayesian multinomial logistic normal models to show that metformin and T2D both associate with shifts in the relative abundance of distinct gut fungi. T2D associates with shifts in the Saccharomycetes and Sordariomycetes fungal classes, while the genera Fusarium and Tetrapisipora most consistently associate with metformin treatment. We confirmed the impact of metformin on individual gut fungi by administering metformin to healthy mice. Thus, metformin and T2D account for subtle, but significant and distinct variation in the gut mycobiome across human populations. This work highlights for the first time that oral pharmaceuticals can confound associations of gut fungi with T2D and warrants the need to consider pharmaceutical interventions in investigations of linkages between metabolic diseases and gut microbial inhabitants.

Manipulating Redox Kinetics using p-n Heterojunction Biservice Matrix as both Cathode Sulfur Immobilizer and Anode Lithium Stabilizer for Practical Lithium-Sulfur Batteries.

As an attractive high-energy-density technology, the practical application of lithium-sulfur (Li-S) batteries is severely limited by the notorious dissolution and shuttle effect of lithium polysulfides (LiPS), resulting in sluggish reaction kinetics and uncontrollable dendritic Li growth. Herein, a p-n typed heterostructure consisting of n-type MoS2 nanoflowers embedded with p-type NiO nanoparticles is designed on carbon nanofibers (denoted as NiO-MoS2 @CNFs) as both cathode sulfur immobilizer and anode Li stabilizer for practical Li-S batteries. Such p-n typed heterostructure is proposed to establish the built-in electric field across the heterointerface for facilitated the positive charge to reach the surface of NiO-MoS2 , meanwhile inherits the excellent LiPS adsorption ability of p-type NiO nanoparticles and catalytic ability of n-type MoS2 . As the anode matrix, the implementation of NiO-MoS2 heterostructure can prevent the growth of Li dendrites by enhancing the lithiophilicity and reducing local current density. The obtained Li-S full battery exhibits an ultra-high areal capacity over 7.3 mAh cm-2 , far exceeding that of current commercial Li-ion batteries. Meanwhile, a stable cycling performance can be achieved under low electrolyte/sulfur ratio of 5.8 µL mg-1 and negative/positive capacity ratio of 1. The corresponding pouch cell maintains high energy density of 305 Wh kg-1 and stable cycling performance under various bending angles.

Decorated Oxidation-resistive deficient Titanium oxide nanotube supported NiFe-nanosheets as high-efficiency electrocatalysts for overall water splitting.

In this study, oxidation-resistive deficient TiO2-x supported NiFe-based electrocatalysts were developed towards efficient and durable water splitting performance. The oxidation-resistive deficient TiO2-x support with oxygen vacancies ensures good stability and electrical conductivity of the catalyst. The decorated NiFe and NiFeP nanosheets serve as efficient catalysts for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), respectively. In 1 M KOH, the NiFe@TiO2-x and NiFeP@TiO2-x electrodes show low overpotential for OER (300 mV) and HER (273 mV) at 100 mA cm-2, respectively, and excellent stability performance in overall water splitting as well. In-situ Raman and theoretical analysis reveals that the in-situ formed Fe3+-doped NiOOH species are essential in catalyzing OER on NiFe@TiO2-x, particularly the electron localization of surface Fe-O bonds offers lower energy barriers for OER elemental reactions and thus enhance its catalytic activity. This work provides an oxide-based catalyst support strategy for the development of stable and active overall water splitting catalysts, and advances the insights on catalytic origin of NiFe-based catalysts as well.

Bile salt hydrolase in non-enterotoxigenic Bacteroides potentiates colorectal cancer.

Bile salt hydrolase (BSH) in Bacteroides is considered a potential drug target for obesity-related metabolic diseases, but its involvement in colon tumorigenesis has not been explored. BSH-expressing Bacteroides is found at high abundance in the stools of colorectal cancer (CRC) patients  with overweight and in the feces of a high-fat diet (HFD)-induced CRC mouse model. Colonization of B. fragilis 638R, a strain with low BSH activity, overexpressing a recombinant bsh gene from B. fragilis NCTC9343 strain, results in increased unconjugated bile acids in the colon and accelerated progression of CRC under HFD treatment. In the presence of high BSH activity, the resultant elevation of unconjugated deoxycholic acid and lithocholic acid activates the G-protein-coupled bile acid receptor, resulting in increased ß-catenin-regulated chemokine (C-C motif) ligand 28 (CCL28) expression in colon tumors. Activation of the ß-catenin/CCL28 axis leads to elevated intra-tumoral immunosuppressive CD25+FOXP3+ Treg cells. Blockade of the ß-catenin/CCL28 axis releases the immunosuppression to enhance the intra-tumoral anti-tumor response, which decreases CRC progression under HFD treatment. Pharmacological inhibition of BSH reduces HFD-accelerated CRC progression, coincident with suppression of the ß-catenin/CCL28 pathway. These findings provide insights into the pro-carcinogenetic role of Bacteroides in obesity-related CRC progression and characterize BSH as a potential target for CRC prevention and treatment.

A COF-coated ordered porous framework as multifunctional polysulfide barrier towards high-performance lithium-sulfur batteries.

The practical application of lithium-sulfur batteries (LSBs) is still hindered by the shuttle effect of lithium polysulfides (LiPS) and slow sulfur conversion kinetics. Herein, a LiPS inhibited covalent organic framework (COF)-coated conductive porous metal oxide design strategy is proposed towards the development of efficient and durable sulfur cathode in LSBs. This strategy is demonstrated by coating a TpPa-1 COF layer on cobalt-decorated titanium oxynirtide (TiOxNy) with a three-dimensional ordered microporous framework (3DOM) structure. In this strategy, the oxygen-deficient TiOxNy framework ensures a good conductivity and structural stability of the cathode during the charge/discharge process. The 3DOM macrospores provide a high capacity for sulfur accommodation and exposes active interfaces, whereas the coated TpPa-1 COF featured with ultrafine microspore offer an effective confinement of LiPS within the 3DOM framework, mitigating its shuttling effect. At the same time, the Co embedded in 3DOM TiOxNy servers as efficient catalyst promoting the sulfur electrochemical reaction. Attributed to these structural superiorities, the 3DOM TpPa-1@Co/TiOxNy/S cathode exhibits excellent performance even under high sulfur loading and low electrolyte condition. This work of using microporous COF coating with conductive macroporous metal oxides offers an effective alternative strategy for the design of practical sulfur battery.

Intestinal peroxisome proliferator-activated receptor α-fatty acid-binding protein 1 axis modulates nonalcoholic steatohepatitis.

BACKGROUND AND AIMS: Peroxisome proliferator-activated receptor α (PPARα) regulates fatty acid transport and catabolism in liver. However, the role of intestinal PPARα in lipid homeostasis is largely unknown. Here, intestinal PPARα was examined for its modulation of obesity and NASH. APPROACH AND RESULTS: Intestinal PPARα was activated and fatty acid-binding protein 1 (FABP1) up-regulated in humans with obesity and high-fat diet (HFD)-fed mice as revealed by using human intestine specimens or HFD/high-fat, high-cholesterol, and high-fructose diet (HFCFD)-fed C57BL/6N mice and PPARA -humanized, peroxisome proliferator response element-luciferase mice. Intestine-specific Ppara or Fabp1 disruption in mice fed a HFD or HFCFD decreased obesity-associated metabolic disorders and NASH. Molecular analyses by luciferase reporter assays and chromatin immunoprecipitation assays in combination with fatty acid uptake assays in primary intestinal organoids revealed that intestinal PPARα induced the expression of FABP1 that in turn mediated the effects of intestinal PPARα in modulating fatty acid uptake. The PPARα antagonist GW6471 improved obesity and NASH, dependent on intestinal PPARα or FABP1. Double-knockout ( Ppara/Fabp1ΔIE ) mice demonstrated that intestinal Ppara disruption failed to further decrease obesity and NASH in the absence of intestinal FABP1. Translationally, GW6471 reduced human PPARA-driven intestinal fatty acid uptake and improved obesity-related metabolic dysfunctions in PPARA -humanized, but not Ppara -null, mice. CONCLUSIONS: Intestinal PPARα signaling promotes NASH progression through regulating dietary fatty acid uptake through modulation of FABP1, which provides a compelling therapeutic target for NASH treatment.

Circulating tumor cell associated white blood cell cluster as a biomarker for metastasis and recurrence in hepatocellular carcinoma.

Background: Recently, an in vivo study demonstrated that circulating tumor cell-associated white blood cell (CTC-WBC) cluster possess much greater potential than single CTCs. We aim to explore the correlation between the CTC-WBC cluster and the clinicopathological characteristics of hepatocellular carcinoma (HCC) patients to seek novel biomarkers for HCC metastasis and recurrence. Methods: We retrospectively analyzed 136 HCC patients from October 2014 to March 2020 who received CTC tests using the CanPatrol CTC enrichment technique. The correlation between the clinical features and total CTCs, EMT-CTCs, and CTC-WBC cluster were analyzed by a chi-square test. The ROC curves were simulated for evaluating the diagnostic performance of CTC parameters in HCC metastasis. Patients were followed up from February 2015 to November 2021, and the relapse-free survival (RFS) was analyzed using the Kaplan-Meier curve. Results: A total of 93.4% (127/136) and 31.6% (43/136) of HCC patients had detectable CTCs and CTC-WBC clusters. Baseline CTC-WBC cluster was closely correlated with microvascular invasion, portal vein tumor thrombus, and extrahepatic metastasis in pre-treatment HCC patients (P <0.05). The simulated ROC curves presented an AUC of 0.821 for the CTC-WBC cluster (sensitivity of 90.0% and specificity of 93.7%) in discriminating metastasis from non-metastatic HCC, which was higher than that for total CTCs (0.718) and EMT-CTCs (0.716). Further follow-up analysis showed that compared to the CTC-WBC cluster negative group (<1/5 ml), patients in the CTC-WBC cluster positive group (≥1/5 ml) presented an increased relapse ratio (60.0% versus 17.9%) and shorter RFS (22.9 versus 53.8 months). Dynamic analysis of CTCs parameters showed that total CTC level, EMT-CTCs proportion, and CTC-WBC cluster were decreased after microwave ablation treatment, while CTC-WBC cluster increased on average 10 months in advance of imaging (MRI) diagnosed recurrence. Conclusion: The CTC-WBC cluster is a promising biomarker for the metastasis diagnosis and prognosis of HCC metastasis. Dynamic monitoring of the CTC-WBC cluster is an effective method for early detection and intervention of HCC recurrence and metastasis.

A bioluminescent probe for NQO1 overexpressing cancer cell imaging in vitro and in vivo.

NAD(P)H quinone oxidoreductase1 (NQO1) is a flavoenzyme that regulates the redox potential level in cells. Overexpression of NQO1 has been proven to be relevant to some malignant tumors. Herein a bioluminescent probe NQO1-Luc equipped with an NQO1-targeting group, trimethyl-locked quinone propionic acid (QPA), was constructed. The reduction of NQO1-Luc could be triggered by NQO1, resulting in the release of free D-luciferin, and concomitantly a bright bioluminescence emission. NQO1-Luc exhibits high selectivity and sensitivity toward NQO1 activity and the capability of distinguishing NQO1-overexpressing cells in vitro and in vivo, which offers a promising tool for investigations of NQO1 related biological processes including tumors in living organisms.

Gut bacteria alleviate smoking-related NASH by degrading gut nicotine.

Tobacco smoking is positively correlated with non-alcoholic fatty liver disease (NAFLD)1-5, but the underlying mechanism for this association is unclear. Here we report that nicotine accumulates in the intestine during tobacco smoking and activates intestinal AMPKα. We identify the gut bacterium Bacteroides xylanisolvens as an effective nicotine degrader. Colonization of B. xylanisolvens reduces intestinal nicotine concentrations in nicotine-exposed mice, and it improves nicotine-exacerbated NAFLD progression. Mechanistically, AMPKα promotes the phosphorylation of sphingomyelin phosphodiesterase 3 (SMPD3), stabilizing the latter and therefore increasing intestinal ceramide formation, which contributes to NAFLD progression to non-alcoholic steatohepatitis (NASH). Our results establish a role for intestinal nicotine accumulation in NAFLD progression and reveal an endogenous bacterium in the human intestine with the ability to metabolize nicotine. These findings suggest a possible route to reduce tobacco smoking-exacerbated NAFLD progression.

Bismuth Gadolinium Oxychloride with a Remarkable Visible-Light-Responsive O2 Evolution Activity Promoted by Iodine Doping.

Visible-light-responsive bismuth-based oxyhalide has recently attracted extensive attention, however, the promotion of its charge separation is still challenging. Herein, we introduce iodine into Bi2 GdO4 Cl to synthetize I-doped Bi2 GdO4 Cl (denoted as yI-Bi2 GdO4 Cl, 0≤y≤2). The incorporation of I- ions is found to enhance light absorption and to accelerate charge separation by combining various characterizations such as density functional theory calculation, photoelectrochemical test, electrochemical impedance spectroscopy, photoluminescence spectrum, and open-circuit voltage decay. The O2 -evolving performances of 1I-Bi2 GdO4 Cl with optimized dopant concentration of I- ion and IrO2 loaded 1I-Bi2 GdO4 Cl are tremendously enhanced by ca. 4 and 45 times compared to pristine Bi2 GdO4 Cl. Notably, The O2 evolution rate reaches as high as 154.8 µmol ⋅ h-1 with an apparent quantum efficiency of ∼1.1 % at 420 nm. The synthetic iodine-doped photocatalyst remains stable after long-term photoreaction, demonstrating its potential in the field of photocatalysis.