Selective Aerobic Oxidation of Csp3-H Bonds Catalyzed by Yeast-Derived Nitrogen, Phosphorus, and Oxygen Codoped Carbon Materials.

Nitrogen, phosphorus, and oxygen codoped carbon catalysts were successfully synthesized using dried yeast powder as a pyrolysis precursor. The yeast-derived heteroatom-doped carbon (yeast@C) catalysts exhibited outstanding performance in the oxidation of Csp3-H bonds to ketones and esters, giving excellent product yields (of up to 98% yield) without organic solvents at low O2 pressure (0.1 MPa). The catalytic oxidation protocol exhibited a broad range of substrates (38 examples) with good functional group tolerance, excellent regioselectivity, and synthetic utility. The yeast-derived heteroatom-doped carbon catalysts showed good reusability and stability after recycling six times without any significant loss of activity. Experimental results and DFT calculations proved the important role of N-oxide (N+-O-) on the surface of yeast@C and a reasonable carbon radical mechanism.

Potential liver damage due to co-exposure to As, Cd, and Pb in mining areas: Association analysis and research trends from a Chinese perspective.

There is global concern regarding the public health hazards of environmental exposure to multiple toxic heavy metals. The effects of toxic heavy metals on liver function have been suggested in previous reports, but the association between exposure to multiple toxic heavy metals and liver function has not been elucidated. The aim of this study was to investigate the effects of exposure to multiple toxic heavy metals, arsenic(As), lead(Pb), and cadmium(Cd), on liver function through population-based and animal studies. A total of 3590 participants were enrolled from the mining areas in Western Hunan Province. The concentrations of As, Pb, and Cd in the urine and plasma samples were determined using quadrupole inductively coupled plasma mass spectrometry (ICP-MS). Bayesian kernel machine regression (BKMR) was employed for the joint association assay. An animal study was conducted to further verify the cumulative effects of metals on liver damage-related parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels. Research trends regarding toxic metals were also explored to obtain in-depth understanding of the current knowledge in this field. Typically, for single-exposure analysis, in most mines, Pb exhibited a significantly negative association with ALT levels, whereas for cumulative effects analysis, when As, Pb, and Cd concentrations were at the 50thpercentile, a significantly negative effect on liver ALT levels was observed. Furthermore, animal studies have shown that co-exposure to As, Pb, and Cd could aggravate liver dysfunction in mice compared to that in the single-metal treated group (p < 0.05). From 1990 to 2019, 1965 projects relating to As, Pb, and Cd research have been initiated, and the total RMB(RenMingBi) funded was approximately 800 million in China, as opposed to 2500 projects in the US with an approximate amount of US$ 1 billion, which is substantially greater than that of China. Finally, from a global viewpoint, scientists should continue to substantially contribute to the field of heavy metal contamination through more extensive academic investigation, global cooperation, and the development of novel control methods. Overall, this study identified that elevated combined concentrations of As, Pb, and Cd were significantly negatively associated with liver function.

MxB impedes the NUP358-mediated HIV-1 pre-integration complex nuclear import and viral replication cooperatively with CPSF6.

BACKGROUND: The human myxovirus resistance 2 (Mx2/MxB) protein was originally found to regulate cytoplasmic-nuclear transport but was recently reported to restrict HIV-1 replication by binding to HIV-1 capsid (CA), preventing uncoating, the nuclear import of pre-integration complex (PIC) and viral DNA integration. This work explores the mechanisms of MxB-mediated HIV-1 inhibition. RESULTS: We demonstrated that MxB represses NUP358-mediated PIC nuclear import and HIV-1 replication. Moreover, MxB's effects on PIC nuclear import and HIV-1 replication depend critically on cofactor cleavage and polyadenylation specificity factor subunit 6 (CPSF6). MxB binds nucleoporin NUP358, blocks NUP358-CA interaction, thereby impeding the nuclear import of HIV-1 PIC with CPSF6 binding to PIC. More intriguingly, CPSF6's role in nuclear import depends on MxB, being a facilitator of HIV-1 nuclear import on its own, but becoming an inhibitor when MxB is present. CONCLUSIONS: Our work establishes that MxB impedes the NUP358-mediated HIV-1 nuclear import and viral replication cooperatively with CPSF6.

Correction to: Description of Wenzhouxiangella salilacus sp. nov., a moderate halophilic bacterium isolated from a salt lake in Xinjiang Province, China.

In the original publication of the article, the deposit accession numbers of strain 15181T in the acknowledgment section were incorrectly provided as "KCTC 62172T and MCCC 1K03442T".

Alkalilacustris brevis gen. nov., sp. nov., isolated from a soda lake.

A Gram-stain-negative, aerobic, non-pigmented and short-rod-shaped bacterium, designated 34079T, was isolated from a water sample of a soda lake in Jilin, a province of China. Strain 34079T grew at 10-50 °C (optimum, 35 °C), pH 7-10 (optimum, pH 8.0-8.5). NaCl was required for growth at the concentration range 1-10.0 % (w/v), with an optimum at 2.5-4 % (w/v). Chemotaxonomic analysis indicated that the sole respiratory quinone was Q-10. The predominant cellular fatty acids (>5 %) were summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c) and C16 : 0. The major polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, three unidentified amino lipids, one unidentified amino phosphoglycolipid, one phosphoglycolipid, one unidentified glycolipid, three unidentified phospholipids and two unidentified lipids. The DNA G+C content was 65.6 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain 34079T formed a distinct lineage in the clade of the family 'Rhodobacteraceae' with the highest sequence similarity of 96.1 % to Pararhodobacter aggregans, followed by Rhodobaca bogoriensis DSM 18756T (95.7 %) and Roseibaca ekhonensis DSM 11469T (94.7 %). The distinct biochemical, chemotaxonomic and phylogenetic differences from the previously described taxa supported that strain 34079T represents a novel species of a new genus, for which the name Alkalilacustris brevis gen. nov., sp. nov. is proposed. The type strain is 34079T (=KCTC 62428T=MCCC 1K03493T).

Pseudomonas mangrovi sp. nov., isolated from mangrove soil.

A Gram-stain-negative, aerobic, non-motile, short-rod-shaped bacterium, designated as strain TC11T, was isolated from rhizosphere soil of mangrove forest (Kandeliaobovata) in Fugong village, Zhangzhou, Fujian, China. Strain TC11T grew at 15-45 °C (optimum, 35 °C), 0-8 % (w/v) NaCl (optimum, 1 %, w/v) and pH 5.5-9.5 (optimum, pH 7.5). Phylogenetic analyses revealed that strain TC11T belonged to a clade of the genus Pseudomonas and showed the highest sequence similarity of 98.4 % to Pseudomonas fluvialis ASS-1T, followed by Pseudomonas oleovorans subsp.oleovorans DSM 1045T (97.9 %), Pseudomonas indoloxydans JCM 14246T (97.7 %), Pseudomonas guguanensis JCM 18416T(97.6 %) and Pseudomonas alcaliphila JCM 10630T (97.5 %) on the basis of their 16S rRNA gene sequences. The DNA G+C content was 64.3 mol%. In silico DNA-DNA hybridization and average nucleotide identity values between strain TC11T and the reference strains were 19-22 % and 72-78 %, respectively. Studies based on the three housekeeping genes, rpoB, gyrB and rpoD, further confirmed that strain TC11T is a novel member of the genus Pseudomonas. The major fatty acids of strain TC11Twere C16 : 0, summed feature 8 (C18 : 1ω6c/C18 : 1ω7c) and summed feature 3 (C16 : 1ω7c/C16 : 1ω6c). The sole isoprenoid quinone was Q-9. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. Based on the phenotypic, chemotaxonomic and phylogenetic properties, strain TC11T represents a novel species of the genus Pseudomonas, for which the name Pseudomonasmangrovi sp. nov., is proposed. The type strain is TC11T (=KCTC 62159=MCCC 1K03499).

Description of Wenzhouxiangella salilacus sp. nov., a moderate halophilic bacterium isolated from a salt lake in Xinjiang Province, China.

A Gram-stain negative, non-motile, strictly aerobic and rod-shaped bacterium, designated as 15181T, was isolated from a salt lake in Xinjiang Province, China. Strain 15181T was able to grow at 10-40 °C (optimum 37 °C), pH 6.0-8.5 (optimum 7.0) and with 1-14% NaCl (optimum 4%, w/v). According to phylogenetic analysis based on 16S rRNA gene sequences, strain 15181T was assigned to the genus Wenzhouxiangella with high 16S rRNA gene sequence similarity of 97.4% to Wenzhouxiangella sediminis XDB06T, followed by Wenzhouxiangella marina KCTC 42284T (95.9%). Strain 15181T exhibited ANI values of 80.0% and 72.0% to W. sediminis XDB06T and W. marina KCTC 42284T, respectively. The in silico DDH analysis revealed that strain 15181T shared 19.1% and 18.7% DNA relatedness with W. sediminis XDB06T and W. marina KCTC 42284T, respectively. Chemotaxonomic analysis showed that the sole respiratory quinone was ubiquinone-8, the major fatty acids included iso-C15:0, iso-C16:0 and summed feature 9 (C16:0 10-methyl and/or iso-C17:1ω9c). The major polar lipids included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unidentified glycolipids, two unidentified phospholipids, two unidentified aminophospholipids and an unidentified lipid. On the basis of phenotypic, genotypic and chemotaxonomic characteristics presented in this study, strain 15181T is concluded to represent a novel species in the genus Wenzhouxiangella, for which the name Wenzhouxiangella salilacus sp. nov. is proposed. The type strain is 15181T (=KCTC 62172T=MCCC 1K03442T).

Kordiimonas pumila sp. nov., isolated from coastal sediment.

A novel Gram-stain-negative, translucent-white, aerobic, motile and rod-shaped strain, designated N18T, was isolated from a coastal sediment sample collected in Zhoushan, Zhejiang Province, China. 16S rRNA gene similarity analysis revealed that strain N18T demonstrated highest similarity to the genus Kordiimonas(95.3-97.2 %). Phylogenetic analysis of 16S rRNA gene sequence showed that strain N18T represented a distinct lineage in the clade consisting of the genus Kordiimonas. Strain N18T was found to grow at 10-37 °C (optimum 28 °C), pH 6.0-8.0 (optimum 7.0) and with 1.0-4.0 % (w/v) NaCl (optimum 2.5 %). The G+C content of the genomic DNA was 55.3 mol%. The major cellular fatty acids were identified as summed feature 3 (comprising iso-C15 : 0 2-OH/C16 : 1ω7c), iso-C17 : 1ω9c and iso-C15 : 0. The polar lipid profile of N18T consisted of phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, an unidentified glycolipid, an unidentified aminoglycolipid, an unidentified aminophospholipid and five unidentified lipids. The respiratory quinone was Q-10. Based on chemotaxonomic, morphological and physiological properties, strain N18T could be distinguished from its closest phylogenetic neighbours. Thus, we propose Kordiimonas pumila sp. nov., the type strain is N18T (=MCCC 1K03436T=KCTC 62164T).

Rhodohalobacter barkolensis sp. nov., isolated from a saline lake and emended description of the genus Rhodohalobacter.

A Gram-stain-negative, non-motile, aerobic, rod-shaped bacterium, designated 15182T, was isolated from a saline lake in China. The novel strain 15182T was able to grow at 10-40 °C (optimum, 37 °C), pH 7.0-8.0 (optimum, 7.5) and with 0.5-4 % NaCl (optimum, 2-3 %, w/v). The phylogenetic analysis based on 16S rRNA gene sequences revealed that strain 15182T was most closely related to the genus Rhodohalobacter by sharing the highest sequence similarity of 97.0 % with Rhodohalobacter halophilus JZ3C29T. Chemotaxonomic analysis showed that the sole respiratory quinone was menaquinone 7, the major fatty acids included C16 : 0 N alcohol and C16 : 1ω11c. The major polar lipids included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, four uncharacterized glycolipids, one uncharacterized phospholipid and two uncharacterized lipids. The genomic DNA G+C content of the strain 15182T was 42.4 mol%. The average nucleotide identity value between 15182T and R. halophilus JZ3C29T was 75.4 %, and the in silico DNA-DNA hybridization value of the two strains was 19.1 %. On the basis of its phenotypic, chemotaxonomic, genotypic and genomic characteristics presented in this study, strain 15182T is suggested to represent a novel species in the genus Rhodohalobacter, for which the name Rhodohalobacter barkolensis sp. nov. is proposed. The type strain is 15182T (=KCTC 62172T=MCCC 1K03442T). An emended description of the genus Rhodohalobacter is also presented.

Confluentibacter flavum sp. nov., Isolated from the Saline Lake.

A Gram-stain-negative, rod-shaped, non-motile, bacterial isolate designated 3BT, was isolated from a saline lake, and subjected to a polyphasic taxonomic investigation. The phylogenetic analysis based on 16S rRNA gene sequence clearly showed an allocation to the genus Confluentibacter with similarity ranging from 95.1 to 98%. OrthoANI values between strain 3BT and related strains of Confluentibacter (< 90%) were lower than the threshold value of 95% ANI relatedness recommended for species demarcation. Strain 3BT grew at 4-35 °C and pH 6.0-8.0 (optimum, 28 °C and pH 6.5) and with 0-3% (w/v) NaCl (optimum, 0.5%). The predominant respiratory quinone was menaquinone-6 (MK-6) and the major fatty acids were iso-C15:0, iso-C15:1 G, iso-C15:0 3-OH, and iso-C17:0 3-OH. The polar lipid profile of strain 3BT comprised phosphatidylethanolamine, one unidentified aminolipid, one aminophospholipid, and three unidentified lipids (L1-3). The DNA G+C content was 33.1 mol%. On the basis of morphological, physiological, and chemotaxonomic characteristics, together with the results of phylogenetic analysis, strain 3BT is described as a novel species in genus Confluentibacter, for which the name Confluentibacter flavum sp. nov. (type strain 3BT = CGMCC115960T = KCTC52969T) is proposed.

Polymorphisms of vascular endothelial growth factor on prognosis in osteosarcoma patients.

OBJECTIVE: We conducted a cohort study to investigate the association of three common SNPs of vascular endothelial growth factors (VEGF) gene (+1612G/A, -634C/G and +936G/C) with clinical outcome of osteosarcoma in a Chinese population. METHODS: A prospective study was conducted. Genotyping analyses of VEGF -2578C/A, +1612G/A, -634C/G and +936G/C were conducted using polymerase chain reaction-restriction fragment length of polymorphism. Multivariate Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% CI of effect of each genotype of VEGF+1612G/A, -634C/G and +936G/C on PFS and osteosarcoma of osteosarcoma. RESULTS: The good response rate was 52.29%, and 116 (68.7%) died during the follow-up period. Patients carrying the +936 CC genotype and C allele showed a significantly more response to chemotherapy than those carrying the wild-type genotype. In the Cox proportional hazards model, patients carrying the VEGF -634 T allele was associated with a significantly decreased risk of PFS and Osteosarcoma (OS). Patients carrying the +936 CC genotype and C allele were associated with a significantly decreased risk of presenting progressive disease or death from osteosarcoma when compared with those carrying the wild-type genotype. However, we observed no significant association between the VEGF -2578C/A and +1612A/G polymorphisms and PFS and Osteosarcoma (OS) in gastric cancer patients. CONCLUSIONS: We found that VEGF -634G/C and +936T/C polymorphisms may affect the prognosis of osteosarcoma patients. These finding may be useful for predicting the clinical outcome of patients with Osteosarcoma (OS). Further studies are greatly needed to confirm the clinical significance of these results.

Radiation-targeted immunotherapy: A new perspective in cancer radiotherapy.

In contemporary oncology, radiation therapy and immunotherapy stand as critical treatments, each with distinct mechanisms and outcomes. Radiation therapy, a key player in cancer management, targets cancer cells by damaging their DNA with ionizing radiation. Its effectiveness is heightened when used alongside other treatments like surgery and chemotherapy. Employing varied radiation types like X-rays, gamma rays, and proton beams, this approach aims to minimize damage to healthy tissue. However, it is not without risks, including potential damage to surrounding normal cells and side effects ranging from skin inflammation to serious long-term complications. Conversely, immunotherapy marks a revolutionary step in cancer treatment, leveraging the body's immune system to target and destroy cancer cells. It manipulates the immune system's specificity and memory, offering a versatile approach either alone or in combination with other treatments. Immunotherapy is known for its targeted action, long-lasting responses, and fewer side effects compared to traditional therapies. The interaction between radiation therapy and immunotherapy is intricate, with potential for both synergistic and antagonistic effects. Their combined use can be more effective than either treatment alone, but careful consideration of timing and sequence is essential. This review explores the impact of various radiation therapy regimens on immunotherapy, focusing on changes in the immune microenvironment, immune protein expression, and epigenetic factors, emphasizing the need for personalized treatment strategies and ongoing research to enhance the efficacy of these combined therapies in cancer care.

In sight the behavior of natural Bletilla striata polysaccharide hydrocolloids by molecular dynamics method.

Plant polysaccharides, distinguished by diverse glycosidic bonds and various cyclic sugar units, constitute a subclass of primary metabolites ubiquitously found in nature. Contrary to common understanding, plant polysaccharides typically form hydrocolloids upon dissolution in water, even though both excessively high and low temperatures impede this process. Bletilla striata polysaccharides (BSP), chosen for this kinetic study due to their regular repeating units, help elucidate the relationship between polysaccharide gelation and temperature. It is suggested that elevated temperatures enhance the mobility of BSP molecular chains, resulting in a notable acceleration of hydrogen bond breakage between BSP and water molecules and consequently, compromising the conformational stability of BSPs to some extent. This study unveils the unique relationship between polysaccharide dissolution processes and temperature from a kinetics perspective. Consequently, the conclusion provides a dynamical basis for comprehending the extraction and preparation of natural plant polysaccharide hydrocolloids, pharmaceuticals and related fields.

Nanoparticles-induced potential toxicity on human health: Applications, toxicity mechanisms, and evaluation models.

Nanoparticles (NPs) have become one of the most popular objects of scientific study during the past decades. However, despite wealth of study reports, still there is a gap, particularly in health toxicology studies, underlying mechanisms, and related evaluation models to deeply understanding the NPs risk effects. In this review, we first present a comprehensive landscape of the applications of NPs on health, especially addressing the role of NPs in medical diagnosis, therapy. Then, the toxicity of NPs on health systems is introduced. We describe in detail the effects of NPs on various systems, including respiratory, nervous, endocrine, immune, and reproductive systems, and the carcinogenicity of NPs. Furthermore, we unravels the underlying mechanisms of NPs including ROS accumulation, mitochondrial damage, inflammatory reaction, apoptosis, DNA damage, cell cycle, and epigenetic regulation. In addition, the classical study models such as cell lines and mice and the emerging models such as 3D organoids used for evaluating the toxicity or scientific study are both introduced. Overall, this review presents a critical summary and evaluation of the state of understanding of NPs, giving readers more better understanding of the NPs toxicology to remedy key gaps in knowledge and techniques.

Lactobacillus rhamnosus GG ameliorates radiation-induced lung fibrosis via lncRNASNHG17/PTBP1/NICD axis modulation.

Radiation-induced pulmonary fibrosis (RIPF) is a major side effect experienced for patients with thoracic cancers after radiotherapy. RIPF is poor prognosis and limited therapeutic options available in clinic. Lactobacillus rhamnosus GG (LGG) is advantaged and widely used for health promotion. However. Whether LGG is applicable for prevention of RIPF and relative underlying mechanism is poorly understood. Here, we reported a unique comprehensive analysis of the impact of LGG and its' derived lncRNA SNHG17 on radiation-induced epithelial-mesenchymal transition (EMT) in vitro and RIPF in vivo. As revealed by high-throughput sequencing, SNHG17 expression was decreased by LGG treatment in A549 cells post radiation and markedly attenuated the radiation-induced EMT progression (p < 0.01). SNHG17 overexpression correlated with poor overall survival in patients with lung cancer. Mechanistically, SNHG17 can stabilize PTBP1 expression through binding to its 3'UTR, whereas the activated PTBP1 can bind with the NICD part of Notch1 to upregulate Notch1 expression and aggravated EMT and lung fibrosis post radiation. However, SNHG17 knockdown inhibited PTBP1 and Notch1 expression and produced the opposite results. Notably, A549 cells treated with LGG also promoted cell apoptosis and increased cell G2/M arrest post radiation. Mice of RIPF treated with LGG decreased SNHG17 expression and attenuated lung fibrosis. Altogether, these data reveal that modulation of radiation-induced EMT and lung fibrosis by treatment with LGG associates with a decrease in SNHG17 expression and the inhibition of SNHG17/PTBP1/Nothch1 axis. Collectively, our results indicate that LGG exerts protective effects in RIPF and SNHG17 holds a potential marker of RIPF recovery in patients with thoracic cancers.

TXNL4B regulates radioresistance by controlling the PRP3-mediated alternative splicing of FANCI.

Ionizing radiation (IR) has been extensively used for cancer therapy, but the radioresistance hinders and undermines the radiotherapy efficacy in clinics greatly. Here, we reported that the spliceosomal protein thioredoxin-like 4B (TXNL4B) is highly expressed in lung tissues from lung cancer patients with radiotherapy. Lung cancer cells with TXNL4B knockdown illustrate increased sensitivity to IR. Mechanistically, TXNL4B interacts with RNA processing factor 3 (PRP3) and co-localizes in the nucleus post-IR. Nuclear localization of PRP3 promotes the alternative splicing of the Fanconi anemia group I protein (FANCI) transcript variants, FANCI-12 and FANCI-13. PRP3 regulates alternative splicing of FANCI toward the two variants, FANCI-12 and FANCI-13. Radioresistance was greatly enhanced through the combination of PRP31 and PRP8, the critical components of core spliceosome promoted by PRP3. Notably, the inhibition of PRP3 to suppress the production of FANCI-12 would deprive PRP31 and PRP8 of such interaction. As a result, cell cycle G2/M arrest was induced, DNA damage repair was delayed, and radiosensitivity was improved. Collectively, our study highlights potential novel underlying mechanisms of the involvement of TXNL4B and alternative splicing in radioresistance. The results would benefit potential cancer radiotherapy.

P53-response circRNA_0006420 aggravates lung cancer radiotherapy resistance by promoting formation of HUR/PTBP1 complex.

BACKGROUND: p53 wild-type lung cancer cells can develop radiation resistance. Circular RNA (circRNA) consists of a family of transcripts with exclusive structures. circRNA is critical in tumorigenesis and is a potential biomarker or therapeutic target. It is uncertain how circRNA expression and functions are regulated post-radiation in p53 wild-type cancer cells. METHODS: A549 or H1299 cells were divided into p53-wt and p53-KO groups by CRISPR/Cas9; both groups were subjected to 4 Gy ionizing radiation (IR: p53-wt-IR and p53-KO-IR). RNA-seq, CCK8, cell cycle, and other functional and mechanism experiments were performed in vivo. p53 gene knockout mice were generated to test the cell results in vitro. RESULTS: circRNAs were found in differential groups. circRNA_0006420 (IRSense) was upregulated in p53-wt cells but had the same expression level as p53-KO cells after radiation, indicating that p53 silencing prevents its upregulation after IR. In the presence of p53, upregulated IRSense post-radiation induces G2/M arrest by regulating DNA damage repair (DDR) pathway-related proteins. Meanwhile, upregulated IRSense post-radiation aggravates the radiation-induced epithelial-mesenchymal transition (EMT). Interestingly, in the presence of p53, it promotes IRSense/HUR/PTBP1 complex formation resulting in the promotion of the radiation-induced EMT. Moreover, c-Jun regulates the upregulation of p53 transcription after radiation treatment. For these lung cancer cells with p53, upregulated IRSense aggravates lung cancer cell proliferation and increases radiation resistance by interacting with HUR (ElAV-like protein 1) and PTBP1 (polypyrimidine tract-binding protein 1) in the nucleus. CONCLUSIONS: Lung cancer cells retaining p53 may upregulate circRNA_0006420 (IRSense) expression post radiation to form an IRSense/HUR/PTBP1 complex leading to radiotherapy resistance. This study furthers our understanding of the roles of circRNA in regulating the effect of radiotherapy and provides novel therapeutic avenues for effective clinical lung cancer therapies.

Potential role of gut microbiota-LCA-INSR axis in high fat-diet-induced non-alcoholic fatty liver dysfunction: From perspective of radiation variation.

Non-alcoholic fatty liver disease (NAFLD) is a progressive disease of the liver covering a range of conditions from hepatic steatosis to liver fibrosis. NAFLD could be induced by High-fat-diet(HFD). Ionizing radiation is widely used in medical diagnosis and therapy as well as is a common risk factor in occupational environment. Whether the exposure of various dose of radiation has effects on HFD-induced NAFLD remains unclear. Here, we reported that radiation exposure promoted HFD-induced NAFLD in a dose-response manner. Furthermore, the gut microbiota composition had significant difference among mice with or without radiation treatment. Specifically, the Bacteroidetes/Firmicutes ratio, the abundance of A. muciniphila, Butyricococcus, and Clostridiaceae decreased significantly in the mice with co-exposure of high dose of radiation and HFD treatment. A fecal transplantation trial (FMT) further verified the role of gut microbiota in the regulation of the liver response to co-exposure of high dose of radiation and HFD treatment. Notably, the gut microbiome analysis showed plasma lithocholic acid (LCA) level increased in the mice with co-exposure of high dose of radiation and HFD treatment. Following antibiotic and probiotic treatments there was a significantly decreased LCA bile acid concentration and subsequent promotion of INSR/PI3K/Akt insulin signaling in the liver tissues. Our results demonstrate that the co-exposure of radiation and HFD aggravates the HFD-induced NAFLD through gut microbiota-LCA-INSR axis. Probiotics supplementation is a potential way to protect against co-exposure of radiation and HFD-induced liver damage. Meanwhile, our study provide a new insight that population with potential HFD-induced damage should pay more attention on preventing from liver damage while exposing radiation.

Helicobacter pylori and Alzheimer's Disease-Related Metabolic Dysfunction: Activation of TLR4/Myd88 Inflammation Pathway from p53 Perspective and a Case Study of Low-Dose Radiation Intervention.

Gut dysbiosis is observed in Alzheimer's disease (AD) and is frequently associated with AD-induced metabolic dysfunction. However, the extent and specific underlying molecular mechanisms triggered by alterations of gut microbiota composition and function mediating AD-induced metabolic dysfunction in AD remain incompletely uncovered. Here, we indicate that Helicobacter pylori (H. pylori) is abundant in AD patients with relative metabolic dysfunction. Fecal microbiota transplantation from the AD patients promoted metabolic dysfunction in mice and increased gut permeability. H. pylori increased gut permeability through activation of the TLR4/Myd88 inflammation pathway in a p53-dependent manner, leading to metabolic dysfunction. Moreover, p53 deficiency reduced bile acid concentration, leading to an increased abundance of H. pylori colonization. Overall, these data identify H. pylori as a key promoter of AD-induced metabolic dysfunction.

Low-dose radiation exaggerates HFD-induced metabolic dysfunction by gut microbiota through PA-PYCR1 axis.

Co-exposure of High-fat-diet (HFD) behavior and environmental low-dose radiation (LDR) is common among majority occupational workers, but the synergism of this co-exposure in metabolic health is poorly understood. This study aimed to investigate the impact of gut microbiota and its metabolites on the regulation of HFD accompanied by LDR-associated with metabolic dysfunction and insulin resistance. Here, we reported that Parasutterella was markedly elevated in the gut microbiota of mice in co-exposure of HFD and LDR, accompanied by increased pyrrolidinecarboxylic acid (PA) level in both intestine and plasma. Transplantation of fecal microbiota from mice with co-exposure HFD and LDR with metabolic dysfunction resulted in increased disruption of metabolic dysfunction, insulin resistance and increased PYCR1 (Pyrroline-5-carboxylate reductase 1) expression. Mechanistically, intestinal barrier was damaged more serious in mice with co-exposure of HFD and LDR, leading high PA level in plasma, activating PYCR1 expression to inhibit insulin Akt/mTOR (AKT kinase-transforming protein/Serine threonine-protein kinase) signaling pathway to aggravate HFD-induced metabolic impairments. This study suggests a new avenue for interventions against western diet companied with low dose radiation exposure-driven metabolic impairments.