Plasmacytosis mimicking multiple myeloma in angioimmunoblastic T-cell lymphoma: A case report and review of literature.

BACKGROUND: Angioimmunoblastic T-cell lymphoma (AITL) is a common subtype of peripheral T-cell lymphoma. Approximately half of patients with AITL may concurrently present with hypergammaglobulinemia. Increased numbers of plasma cells in the bone marrow are commonly observed at diagnosis. These tumors mimic plasma cell myelomas, hindering a conundrum of clinical diagnoses and potentially delaying appropriate treatment. CASE SUMMARY: A 78-year-old woman experienced poor appetite, weight loss of 5 kg, fatigue 2 months before presentation, and shortness of breath 2 d before presentation, but no fever or night sweats. Physical examination revealed splenomegaly and many palpable masses over the bilateral axillary regions, approximately > 2 cm in size, with rubbery consistency and no tenderness. Blood tests revealed anemia and thrombocytopenia, lactate dehydrogenase level of 153 U/L, total protein level of 10.9 g/dL, albumin to globulin ratio of 0.2, and immunoglobulin G level more than the upper limit of 3000 mg/dL. The free kappa and lambda light chain concentrations were 451 and 614 mg/L, respectively. A pathological examination confirmed the diagnosis of AITL. The initial treatment was the cyclophosphamide, epirubicin, vincristine, and prednisolone regimen. Following this treatment, pleural effusion was controlled, and the patient was discharged in a stable condition and followed up in our outpatient department. CONCLUSION: This report highlights the importance of differentiating reactive plasmacytosis from plasma cell myeloma in patients with hypergammaglobulinemia. A precise diagnosis of AITL requires a comprehensive evaluation, involving clinical, immunophenotypic, and histological findings conducted by a multidisciplinary team to ensure appropriate treatment.

The efficacy and safety of EGFR-TKI in recurrent/metastatic nasopharyngeal carcinoma patients: A systematic review and meta-analysis.

Objectives: EGFR-tyrosine kinase inhibitor (TKI) is used to treat recurrent and metastatic nasopharyngeal carcinoma (rmNPC). This meta-analysis aims to study the efficacy and safety of EGFR-TKI in treating patients with rmNPC. Methods: We conducted a systematic search of PubMed, Embase, and Web of Science up to November 2023, and included literature that met the criteria. We extracted objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and adverse reaction-related events and performed meta-analysis using Stata 14.0. Results: A total of nine articles were included. The summary results showed that the ORR for patients treated with EGFR-TKI for rmNPC was 38% (95% CI = 27%-49%), the DCR was 71% (95% CI = 61%-80%), the mPFS was 6.29 months (95% CI = 5.22-7.35), and the mOS was 15.94 months (95% CI = 14.68-17.20). The most common grade 3-4 adverse reaction events in these patients were mucositis, nasopharyngeal necrosis, and oral ulceration. We found an incidence rate of 49% (95% CI = 38%-61%) for grade 3-4 adverse events (AEs). The anti-PD1 combined with TKI treatment method is more effective than the EGFR-TKI alone for treating rmNPC. Conclusion: The study shows that EGFR-TKI has good efficacy in treating rmNPC but does not translate into survival benefits and owns a high incidence of grade 3-4 AEs. More RCT trials are needed in the future to verify the efficacy of anti-PD1 combined with TKI treatment method.

Berbamine ameliorates DSS-induced colitis by inhibiting peptidyl-arginine deiminase 4-dependent neutrophil extracellular traps formation.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with immune dysregulation affecting colon inflammatory response. Recent studies have highlighted that neutrophil extracellular traps (NETs) play an important role in the pathogenesis of UC. Berbamine (BBM), one of the bioactive ingredients extracted from Chinese herbal medicine Berberis vulgaris L, has attracted intensive attentions due to its significant anti-inflammatory activity and a marketing drug for treating leukemia in China. However, the exact role and potential molecular mechanism of BBM against UC remains elusive. In the present study, our results showed that BBM could markedly improve the pathological phenotype and the colon inflammation in mice with dextran sulfate sodium (DSS)-induced colitis. Then, comprehensive approaches combining network pharmacology and molecular docking analyses were employed to predict the therapeutic potential of BBM in treating UC by peptidyl-arginine deiminase 4 (PAD4), a crucial molecule involved in NETs formation. The molecular docking results showed BBM had a high affinity for PAD4 with a binding energy of -9.3 kcal/mol Moreover, PAD4 expression and NETs productions, including citrullination of histone H3 (Cit-H3), neutrophil elastase (NE), myeloperoxidase (MPO) in both neutrophils and colonic tissue were reduced after BBM administration. However, in the mice with DSS-induced colitis pretreated with GSK484, a PAD4-specific inhibitor, BBM could not further reduce disease related indexes, expression of PAD4 and NETs productions. Above all, the identification of PAD4 as a potential target for BBM to inhibit NETs formation in colitis provides novel insights into the development of BBM-derived drugs for the clinical management of UC.

Early administration of Wumei Wan inhibit myeloid-derived suppressor cells via PI3K/Akt pathway and amino acids metabolism to prevent colitis-associated colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Wumei Wan (WMW), a traditional Chinese medicine prescription, has been proved to be effective in treating Colitis-associated colorectal cancer (CAC), but it has not been proven to be effective in different stages of CAC. AIM OF THE STUDY: The purpose of our study is to investigate the therapeutic effect and mechanism of WMW on the progression of CAC. MATERIALS AND METHODS: Azioximethane (AOM) and dextran sulfate sodium (DSS) were used to treat mice for the purpose of establishing CAC models. WMW was administered in different stages of CAC. The presentative chemical components in WMW were confirmed by LC-MS/MS under the optimized conditions. The detection of inflammatory cytokines in the serum and colon of mice were estimated by qRT-PCR and ELISA. The changes of T cells and myeloid-derived suppressor cells (MDSCs) in each group were detected by flow cytometry. The metabolic components in serum of mice were detected by UPLC-MS/MS. Expression of genes and proteins were detected by eukaryotic transcriptomics and Western blot to explore the key pathway of WMW in preventing CAC. RESULTS: WMW had significant effect on inhibiting inflammatory responses and tumors during the early development stage of CAC when compared to other times. WMW increased the length of mice's colons, reduced the level of IL-1ß, IL-6, TNF-α in colon tissues, and effectively alleviated colonic inflammation, and improved the pathological damage of colon tissues. WMW could significantly reduce the infiltration of MDSCs in the spleen, increase CD4+ T cells and CD8+ T cells in the spleen of CAC mice, and effectively reform the immune microenvironment in CAC mice. Transcriptomics analysis revealed that 2204 genes had different patterns of overlap in the colon tissues of mice between control group, AOM + DSS group, and early administration of WMW group. And KEGG enrichment analysis showed that PI3K/Akt signaling pathway, ECM-receptor interaction, IL-17 signaling pathway, MAPK signaling pathway, pancreatic secretion, thermogenesis, and Rap1 signaling pathway were all involved. The serum metabolomics results of WMW showed that the metabolic compositions of the control group, AOM + DSS group and the early stage of WMW were different, and 42 differential metabolites with the opposite trends of changes were screened. The metabolic pathways mainly included pyrimidine metabolism, glycine, serine and threonine metabolism, tryptophan metabolism, and purine metabolism. And amino acids and related metabolites may play an important role in WMW prevention of CAC. CONCLUSION: WMW can effectively prevent the occurrence and development of CAC, especially in the initial stage. WMW can reduce the immune infiltration of MDSCs in the early stage. Early intervention of WMW can improve the metabolic disorder caused by AOM + DSS, especially correct the amino acid metabolism. PI3K/Akt signaling pathway was inhabited in early administration of WMW, which can regulate the amplification and function of MDSCs.

Temperature drives microbial communities in anaerobic digestion during biogas production from food waste.

Resource depletion and climate changes due to human activities and excessive burning of fossil fuels are the driving forces to explore alternatives clean energy resources. The objective of this study was to investigate the potential of potato peel waste (PPW) at various temperatures T15 (15 °C), T25 (25 °C), and T35 (35 °C) in anaerobic digestion (AD) for biogas generation. The highest biogas and CH4 production (117 mL VS-g and 74 mL VS-g) was observed by applying 35 °C (T35) as compared with T25 (65 mL VS-g and 22 mL VS-g) on day 6. Changes in microbial diversity associated with different temperatures were also explored. The Shannon index of bacterial community was not significantly affected, while there was a positive correlation of archaeal community with the applied temperatures. The bacterial phyla Firmicutes were strongly affected by T35 (39%), whereas Lactobacillus was the dominant genera at T15 (27%). Methanobacterium and Methanosarcina, as archaeal genera, dominated in T35 temperature reactors. In brief, at T35, Proteiniphilum and Methanosarcina were positively correlated with volatile fatty acids (VFAs) concentration. Spearman correlation revealed dynamic interspecies interactions among bacterial and archaeal genera; facilitating the AD system. This study revealed that temperature variations can enhance the microbial community of the AD system, leading to increased biogas production. It is recommended for optimizing the AD of food wastes.

Saxibacter everestensis gen. nov., sp. nov., A Novel Member of the Family Brevibacteriaceae, Isolated from the North Slope of Mount Everest.

We isolated and analyzed a novel, Gram-stain-positive, aerobic, rod-shaped, non-motile actinobacterium, designated as strain ZFBP1038T, from rock sampled on the north slope of Mount Everest. The growth requirements of this strain were 10-37 °C, pH 4-10, and 0-6% (w/v) NaCl. The sole respiratory quinone was MK-9, and the major fatty acids were anteiso-C15:0 and iso-C17:0. Peptidoglycan containing meso-diaminopimelic acid, ribose, and glucose were the major cell wall sugars, while polar lipids included diphosphatidyl glycerol, phosphatidyl glycerol, an unidentified phospholipid, and an unidentified glycolipid. A phylogenetic analysis based on 16S rRNA gene sequences showed that strain ZFBP1038T has the highest similarity with Spelaeicoccus albus DSM 26341 T (96.02%). ZFBP1038T formed a distinct monophyletic clade within the family Brevibacteriaceae and was distantly related to the genus Spelaeicoccus. The G + C content of strain ZFBP1038T was 63.65 mol% and the genome size was 4.05 Mb. Digital DNA-DNA hybridization, average nucleotide identity, and average amino acid identity values between the genomes of strain ZFBP1038T and representative reference strains were 19.3-25.2, 68.0-71.0, and 52.8-60.1%, respectively. Phylogenetic, phenotypic, and chemotaxonomic characteristics as well as comparative genome analyses suggested that strain ZFBP1038T represents a novel species of a new genus, for which the name Saxibacter gen. nov., sp. nov. was assigned with the type strain Saxibacter everestensis ZFBP1038T (= EE 014 T = GDMCC 1.3024 T = JCM 35335 T).

Temperature-dependent transformation of microbial community: A systematic approach to analyzing functional microbes and biogas production.

The stability and effectiveness of the anaerobic digestion (AD) system are significantly influenced by temperature. While majority research has focused on the composition of the microbial community in the AD process, the relationships between functional gene profile deduced from gene expression at different temperatures have received less attention. The current study investigates the AD process of potato peel waste and explores the association between biogas production and microbial gene expression at 15, 25, and 35 °C through metatranscriptomic analysis. The production of total biogas decreased with temperature at 15 °C (19.94 mL/g VS), however, it increased at 35 °C (269.50 mL/g VS). The relative abundance of Petrimonas, Clostridium, Aminobacterium, Methanobacterium, Methanothrix, and Methanosarcina were most dominant in the AD system at different temperatures. At the functional pathways level 3, α-diversity indices, including Evenness (Y = 5.85x + 8.85; R2 = 0.56), Simpson (Y = 2.20x + 2.09; R2 = 0.33), and Shannon index (Y = 1.11x + 4.64; R2 = 0.59), revealed a linear and negative correlation with biogas production. Based on KEGG level 3, several dominant functional pathways associated with Oxidative phosphorylation (ko00190) (25.09, 24.25, 24.04%), methane metabolism (ko00680) (30.58, 32.13, and 32.89%), and Carbon fixation pathways in prokaryotes (ko00720) (27.07, 26.47, and 26.29%), were identified at 15 °C, 25 °C and 35 °C. The regulation of biogas production by temperature possibly occurs through enhancement of central function pathways while decreasing the diversity of functional pathways. Therefore, the methanogenesis and associated processes received the majority of cellular resources and activities, thereby improving the effectiveness of substrate conversion to biogas. The findings of this study illustrated the crucial role of central function pathways in the effective functioning of these systems.

A novel UV-resistant bacterium Sphingomonas endolithica sp. nov., and genomic analysis, isolated from the north slope of Mount Everest.

Gram-stain-negative, aerobic, rod-shaped, non-motile bacterium strain ZFBP2030T was isolated from a rock on the North slope of Mount Everest. This strain contained a unique ubiquinone-10 (Q-10) as a predominant respiratory quinone. Among the tested fatty acids, the strain contained summed feature 8, C14:0 2OH, and C16:0, as major cellular fatty acids. The polar lipid profile contained phosphatidyl glycerol, phosphatidyl ethanolamine, three unidentified phospholipids, two unidentified aminolipids, and six unidentified lipids. The cell-wall peptidoglycan was a meso-diaminopimelic acid, and cell-wall sugars were ribose and galactose. Phylogenetic analyses based on 16S rRNA gene sequence revealed that strain ZFBP2030T was a member of the genus Sphingomonas, exhibiting high sequence similarity to the 16S rRNA gene sequences of Sphingomonas aliaeris DH-S5T (97.9%), Sphingomonas alpina DSM 22537T (97.3%) and Sphingomonas hylomeconis CCTCC AB 2013304T (97.0%). The 16S rRNA gene sequence similarity between ZFBP2030T and other typical strains was less than 97.0%. The average amino acid identity values, average nucleotide identity, and digital DNA-DNA hybridization values between strain ZFBP2030T and its highest sequence similarity strains were 56.9-79.9%, 65.1-82.2%, and 19.3-25.8%, respectively. The whole-genome size of the novel strain ZFBP2030T was 4.1 Mbp, annotated with 3838 protein-coding genes and 54 RNA genes. Moreover, DNA G + C content was 64.7 mol%. Stress-related functions predicted in the subsystem classification of the strain ZFBP2030T genome included osmotic, oxidative, cold/heat shock, detoxification, and periplasmic stress responses. The overall results of this study clearly showed that strain ZFBP2030T is a novel species of the genus Sphingomonas, for which the name Sphingomonas endolithica sp. nov. is proposed. The type of strain is ZFBP2030T (= EE 013T = GDMCC 1.3123T = JCM 35386T).

Comparative genomics reveals environmental adaptability and antimicrobial activity of a novel Streptomyces isolated from soil under black Gobi rocks.

A novel Streptomyces strain, designated 3_2T, was isolated from soil under the black Gobi rock sample of Northwest China. The taxonomic position of this strain was revealed by a polyphasic approach. Comparative analysis of the 16S rRNA gene sequences indicated that 3_2T was closely related to the members of the genus Streptomyces, with the highest similarity to Streptomyces rimosus subsp. rimosus CGMCC 4.1438 (99.17%), Streptomyces sioyaensis DSM 40032 (98.97%). Strain 3_2T can grow in media up to 13% NaCl. The genomic DNA G + C content of strain 3_2T was 69.9%. We obtained the genomes of 22 Streptomyces strains similar to strain 3_2T, compared the average nucleotide similarity, dDDH and average amino acid identity, and found that the genomic similarity of the new isolate 3_2T to all strains was below the threshold for interspecies classification. Chemotaxonomic data revealed that strain 3_2T possessed MK-9 (H6) and MK-9 (H8) as the major menaquinones. The cell wall contained LL-diaminopimelic acid (LL-DAP) and the whole-cell sugars were ribose and glucose. The major fatty acid methyl esters were iso-C16:0 (23.6%) and anteiso-C15:0 (10.4%). The fermentation products of strain 3_2T were inhibitory to Staphylococcus aureus and Bacillus thuringiensi. The genome of 3_2T was further predicted using anti-smash and the strain was found to encode the production of 41 secondary metabolites, and these gene clusters may be key to the good inhibitory activity exhibited by the strain. Genomic analysis revealed that strain 3_2T can encode genes that produce a variety of genes in response to environmental stresses, including cold shock, detoxification, heat shock, osmotic stress, oxidative stress, and these genes may play a key role in the harsh environment in which the strain can survive. Therefore, this strain represents a novel Streptomyces species, for which the name Streptomyces halobius sp. nov. is proposed. The type strain is 3_2T (= JCM 34935T = GDMCC 4.217T).

Role of gut microbiota and bacterial metabolites in mucins of colorectal cancer.

Colorectal cancer (CRC) is a major health burden, accounting for approximately 10% of all new cancer cases worldwide. Accumulating evidence suggests that the crosstalk between the host mucins and gut microbiota is associated with the occurrence and development of CRC. Mucins secreted by goblet cells not only protect the intestinal epithelium from microorganisms and invading pathogens but also provide a habitat for commensal bacteria. Conversely, gut dysbiosis results in the dysfunction of mucins, allowing other commensals and their metabolites to pass through the intestinal epithelium, potentially triggering host responses and the subsequent progression of CRC. In this review, we summarize how gut microbiota and bacterial metabolites regulate the function and expression of mucin in CRC and novel treatment strategies for CRC.

The AGH score is a predictor of disease-free survival and targeted therapy efficacy after liver transplantation in patients with hepatocellular carcinoma.

BACKGROUND: Liver transplantation (LT) is the "cure" therapy for patients with hepatocellular carcinoma (HCC). However, some patients encounter HCC recurrence after LT. Unfortunately, there is no effective methods to identify the LT patients who have high risk of HCC recurrence and would benefit from adjuvant targeted therapy. The present study aimed to establish a scoring system to predict HCC recurrence of HCC patients after LT among the Chinese population, and to evaluate whether these patients are suitable for adjuvant targeted therapy. METHODS: Clinical data of HCC patients who underwent LT from March 2015 to June 2019 were retrospectively collected and analyzed. RESULTS: A total of 201 patients were included in the study. The multivariate Cox analysis suggested that preoperative alpha-fetoprotein (AFP) > 200 µg/L (HR = 2.666, 95% CI: 1.515-4.690; P = 0.001), glutamyl transferase (GGT) > 96 U/L (HR = 1.807, 95% CI: 1.012-3.224; P = 0.045), and exceeding the Hangzhou criteria (HR = 2.129, 95% CI: 1.158-3.914; P = 0.015) were independent risk factors for poor disease-free survival (DFS) in patients with HCC who underwent LT. We established an AFP-GGT-Hangzhou (AGH) scoring system based on these factors, and divided cases into high-, moderate-, and low-risk groups. The differences in overall survival (OS) and disease-free survival (DFS) rates among the three groups were significant (P < 0.05). The efficacy of the AGH scoring system to predict DFS was better than that of the Hangzhou criteria, UCSF criteria, Milan criteria, and TNM stage. Only in the high-risk group, we found that lenvatinib significantly improved prognosis compared with that of the control group (P < 0.05). CONCLUSIONS: The AGH scoring system provides a convenient and effective way to predict HCC recurrence after LT in HCC patients in China. Patients with a high-risk AGH score may benefit from lenvatinib adjuvant therapy after LT.

Genomic Insights into the Radiation-Resistant Capability of Sphingomonas qomolangmaensis S5-59T and Sphingomonas glaciei S8-45T, Two Novel Bacteria from the North Slope of Mount Everest.

Mount Everest provides natural advantages to finding radiation-resistant extremophiles that are functionally mechanistic and possess commercial significance. (1) Background: Two bacterial strains, designated S5-59T and S8-45T, were isolated from moraine samples collected from the north slope of Mount Everest at altitudes of 5700m and 5100m above sea level. (2) Methods: The present study investigated the polyphasic features and genomic characteristics of S5-59T and S8-45T. (3) Results: The major fatty acids and the predominant respiratory menaquinone of S5-59T and S8-45T were summed as feature 3 (comprising C16:1 ω6c and/or C16:1 ω7c) and ubiquinone-10 (Q-10). Phylogenetic analyses based on 16S rRNA sequences and average nucleotide identity values among these two strains and their reference type strains were below the species demarcation thresholds of 98.65% and 95%. Strains S5-59T and S8-45T harbored great radiation resistance. The genomic analyses showed that DNA damage repair genes, such as mutL, mutS, radA, radC, recF, recN, etc., were present in the S5-59T and S8-45T strains. Additionally, strain S5-59T possessed more genes related to DNA protection proteins. The pan-genome analysis and horizontal gene transfers revealed that strains of Sphingomonas had a consistently homologous genetic evolutionary radiation resistance. Moreover, enzymatic antioxidative proteins also served critical roles in converting ROS into harmless molecules that resulted in resistance to radiation. Further, pigments and carotenoids such as zeaxanthin and alkylresorcinols of the non-enzymatic antioxidative system were also predicted to protect them from radiation. (4) Conclusions: Type strains S5-59T (=JCM 35564T =GDMCC 1.3193T) and S8-45T (=JCM 34749T =GDMCC 1.2715T) represent two novel species of the genus Sphingomonas with the proposed name Sphingomonas qomolangmaensis sp. nov. and Sphingomonas glaciei sp. nov. The type strains, S5-59T and S8-45T, were assessed in a deeply genomic study of their radiation-resistant mechanisms and this thus resulted in a further understanding of their greater potential application for the development of anti-radiation protective drugs.

Paracoccus everestensis sp. nov., a novel bacterium with great antioxidant capacity isolated from the north slope of Mount Everest.

A bacterial strain, designated S8-55T, was isolated from moraine samples collected from the north slope of Mount Everest at an altitude of 5 500 m above sea level. The purpose of this study was to describe a novel species and its characteristics, through genome sequencing and analysis of the relationship between the members of the genus Paracoccus, and explore the antioxidant capacity of strain S8-55T. The polyphasic study confirmed the affiliation of strain S8-55T with the genus Paracoccus. Strain S8-55T was aerobic, Gram-negative and oxidase- and catalase positive. Cells were orange-pigmented, ellipsoid and had no spore formation, no flagella and no motility. Strain S8-55T grow at 10-37 °C, pH 7-11 and without NaCl. Ubiquinone 10 was its predominant respiratory menaquinone. The polar lipids of strain S8-55T were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, an unidentified phospholipid, an unidentified aminolipid and three unidentified lipids. Its major fatty acids were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The G+C content was 64.3 mol%. The phylogenetic analysis based on the 16S rRNA sequence showed that strain S8-55T was closely related to Paracoccus angustae E6T (97.9 %), Paracoccus aerius 011410T (97.9 %) and Paracoccus hibisci THG-T2.8T (97.8 %). The average nucleotide identity values among strain S8-55T and P. angustae CCTCC AB 2015056T, P. aerius KCTC 42845T and P. hibisci CCTCC AB 2016181T were 84.1, 84.5 and 76.3 %, respectively. The genome of strain S8-55T contained antioxidant genes such as oxyR, recD, katE, recD and rpoH. Based on its morphological, physiological and chemical taxonomic characteristics, strain S8-55T (=JCM 35 227T=GDMCC 1.3026T) should be classified as a novel species of the genus Paracoccus with the proposed name Paracoccus everestensis sp. nov.

Purification, Identification, and Properties of a Novel Carotenoid Produced by Arthrobacter sp. QL17 Isolated from Mount Qomolangma.

The genus Arthrobacter is a source of many natural products that are critical in the development of new medicines. Here, we isolated a novel carotenoid from Arthrobacter sp. QL17 and characterized its properties. The carotenoid was extracted with methanol, and purified by column chromatography and semi-preparative HPLC. Based on micrOTOF-Q and NMR analyses, the pigment was chemically characterized as 2,2'-((((1E,3E,5E,7E,9E,11E,13E,15E,17E,19E)-3,7,14,18-tetramethylicosa-1,3,5,7,9,11,13,15,17,19-decaene-1,20-diyl)bis(2,2,4-trimethylcyclohex-3-ene-3,1-diyl)) bis(ethan-2-yl-1-ylidene))bi(propane-1,3-diol), and named arthroxanthin. The biological activities of arthroxanthin were evaluated with DPPH, ABTS and MTT assays. Arthroxanthin exhibited excellent radical scavenging properties, as shown for 2, 20-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-n-(3,2-ethyl-benzothiazole-6-sulfonic acid) ammonium salt (ABTS), respectively, with IC50s of 69.8 and 21.5 µg/mL. It also showed moderate anticancer activities against HepG2, Hela, MDAB-231, SW480, and MKN-45 with IC50 values of 107.6, 150.4, 143.4, 195.9, and 145.5 µg/mL, respectively. Therefore, arthroxanthin derived from Arthrobacter sp. QL17 may be a potent antioxidant and anticancer agent for food and pharmaceutical use.

Multidimensional sleep health is associated with physical frailty in a national sample of Taiwanese community-dwelling older adults: Sex matters.

OBJECTIVES: Although individual sleep characteristics are related to frailty, these characteristics do not occur separately. A multidimensional measure of sleep might provide a better estimation of frailty compared to isolated sleep characteristics. This study investigated the association of a multidimensional measure of sleep health with frailty both across and within sex groups. DESIGN: Data were from the Taiwan Longitudinal Study on Aging (2011), a survey with a nationally representative sample of Taiwanese older adults (N = 2,015). Frailty was defined using the Fried criteria. Self-reported sleep during the past month was used to conceptualize the five sleep health dimensions in the SATED model. Their relationship was estimated using logistic regression analysis adjusting for sociodemographic characteristics (age, sex, education), health status (comorbidity, cognitive function, pain, depressive symptoms [excluding items overlapping with frailty and sleep]), and health risk behaviors (drinking, smoking, lack of exercise). RESULTS: Having a better sleep health composite score was significantly related to lower odds of being frail in both sexes adjusting for sociodemographic characteristics. This association remained significant among women but not among men after adding health and risk behaviors to the models. Satisfaction and alertness in both sexes and duration among women were significantly associated with frailty adjusting for sociodemographic characteristics. Only alertness among men was significantly related to frailty in the model with all covariates. CONCLUSIONS: Our findings show that having better sleep health across multiple dimensions is related to a lower risk of being frail, with differential risks for women and men.

A new bacterial tRNA enhances antibiotic production in Streptomyces by circumventing inefficient wobble base-pairing.

We report the discovery and functional characterization of a new bacterial tRNA species. The tRNA-Asp-AUC, from a fast-growing desert streptomycete, decodes GAU codons. In the absence of queuosine tRNA anticodon modification in streptomycetes, the new tRNA circumvents inefficient wobble base-pairing during translation. The tRNA, which is constitutively expressed, greatly enhances synthesis of 4 different antibiotics in the model mesophilic species Streptomyces coelicolor, including the product of a so-called cryptic pathway, and increases yields of medically-important antibiotics in other species. This can be rationalised due to increased expression of both pleiotropic and pathway-specific transcriptional activators of antibiotic biosynthesis whose genes generally possess one or more GAT codons; the frequency of this codon in these gene sets is significantly higher than the average for streptomycete genes. In addition, the tRNA enhances production of cobalamin, a precursor of S-adenosyl methionine, itself an essential cofactor for synthesis of many antibiotics. The results establish a new paradigm of inefficient wobble base-pairing involving GAU codons as an evolved strategy to regulate gene expression and, in particular, antibiotic biosynthesis. Circumventing this by expression of the new cognate tRNA offers a generic strategy to increase antibiotic yields and to expand the repertoire of much-needed new bioactive metabolites produced by these valuable bacteria.

High Proportions of Radiation-Resistant Strains in Culturable Bacteria from the Taklimakan Desert.

The Taklimakan Desert located in China is the second-largest shifting sand desert in the world and is known for its harsh conditions. Types of γ-rays or UV radiation-resistant bacterial strains have been isolated from this desert. However, there is no information regarding the proportions of the radiation-resistant strains in the total culturable microbes. We isolated 352 bacterial strains from nine sites across the Taklimakan Desert from north to south. They belong to Actinobacteria, Firmicutes, Proteobacteria, and Bacteroidetes. The phylum Actinobacteria was the most predominant in abundance and Firmicutes had the highest species richness. Bacteroidetes had the lowest abundance and was found in four sites only, while the other three phyla were found in every site but with different distribution profiles. After irradiating with 1000 J/m2 and 6000 J/m2 UV-C, the strains with survival rates higher than 10% occupied 72.3% and 36.9% of all culturable bacteria, respectively. The members from Proteobacteria had the highest proportions, with survival rates higher than 10%. After radiation with 10 kGy γ-rays, Kocuria sp. TKL1057 and Planococcus sp. TKL1152 showed higher radiation-resistant capabilities than Deinococcus radiodurans R1. Besides obtaining several radiation-resistant extremophiles, this study measured the proportions of the radiation-resistant strains in the total culturable microbes for the first time. This study may help to better understand the origin of radioresistance, especially by quantitatively comparing proportions of radiation-resistant extremophiles from different environments in the future.

Secoisolariciresinol diglucoside induces pyroptosis by activating caspase-1 to cleave GSDMD in colorectal cancer cells.

Secoisolariciresinol diglucoside (SDG) is the main component of lignans with various biological activities, including anticancer activity. However, whether SDG has obvious anticancer effects on colorectal cancer (CRC) is unclear. Pyroptosis, a form of programmed cell death, has received increasing attention in cancer-related research. In this study, we aimed to test the anticancer properties and relatecd functional mechanisms of SDG. we found that SDG not only inhibited the cell viability of HCT116 cells, but also induced HCT116 cells to swell with apparent large bubbles, which are typical signs of pyroptosis. Furthermore, SDG induced cell pyroptosis by enhancing cleavage of the N-terminal fragment of gasdermin D (GSDMD) in CRC cells, accompanied by increased caspase-1 cleavage. Consistent with this, SDG-induced GSDMD-N-terminal fragment cleavage and pyroptosis were reduced by siRNA-mediated silencing of caspase-1 or treatment with the specific caspase-1 inhibitor VX-765 treatment, suggesting that active caspase-1 further induces pyroptosis. A mechanistic study showed that SDG induced reactive oxygen species (ROS) accumulation and inhibits phosphatidylinositol 3-kinase (PI3K) phosphorylation and increases pyroptosis, while increasing GSDMD and caspase-1 cleavage and enhancing expression of BCL2-associated X (BAX), which could be rescued by the ROS scavenger (NAC), suggesting that SDG-induced GSDME-dependent pyroptosis is related to the ROS/PI3K/AKT/BAX-mitochondrial apoptotic pathway. In vivo results showed that SDG significantly inhibited tumor growth and induced pyroptosis in the HCT116-CRC nude mouse model. In conclusion, our findings suggest that the anticancer activity of SDG in CRC is associated with the induction of GSDMD-dependent pyroptosis by SDG through the generation of ROS/P13K/AKT/BAK-mitochondrail apoptosis pathway, providing insights into SDG in its potential new application in cancer treatment.

Sphingomonas radiodurans sp. nov., a novel radiation-resistant bacterium isolated from the north slope of Mount Everest.

A bacterial strain, designated S9-5T, was isolated from moraine samples collected from the north slope of Mount Everest at an altitude of 5 500 m above sea level. A polyphasic study confirmed the affiliation of the strain with the genus Sphingomonas. Strain S9-5T was an aerobic, Gram-stain-negative, non-spore-forming, non-motile and rod-shaped bacterium that could grow at 10-40 °C, pH 5-8 and with 0-9 % (w/v) NaCl. Q-10 was its predominant respiratory menaquinone. Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, an unidentified phospholipid, an unidentified aminophospholipid and eight unidentified lipids comprised the polar lipids of strain S9-5T. Its major fatty acids were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) and C16 : 0. The G+C content was 65.75mol%. Phylogenetic analysis based on 16S rRNA sequences showed that strain S9-5T was phylogenetically closely related to Sphingomonas panaciterrae DCY91T (98.17 %), Sphingomonas olei K-1-16T (98.11 %) and Sphingomonas mucosissima DSM 17494T (97.39 %). The average nucleotide identity values among strain S9-5T and Sphingomonas panaciterrae DCY91T, Sphingomonas olei K-1-16T and Sphingomonas mucosissima DSM 17494T were 78.82, 78.87 and 78.29 %, respectively. Based on the morphological, physiological and chemotaxonomic data, strain S9-5T (=JCM 34750T=GDMCC 1.2714T) should represent a novel species of the genus Sphingomonas, for which we propose the name Sphingomonas radiodurans sp. nov.

Streptomyces gobiensis sp. nov., an antimicrobial producing actinobacterium isolated from soil under black Gobi rocks.

A novel actinomycete, strain 1_25T, was isolated from soil under a black Gobi rock sample from Shuangta, PR China, and characterized using a polyphasic taxonomic approach. The results of comparative analysis of the 16S rRNA gene sequences indicated the 1_25T represented a member of the genus Streptomyces. Chemotaxonomic data revealed that 1_25T possessed MK-9(H8) as the major menaquinone. The cell wall contained ll-diaminopimelic acid (ll-DAP) and the whole-cell sugar pattern consisted of ribose, glucose and galactose. Major fatty acid methyl esters were observed to be iso-C16 : 0 (23.6 %), and anteiso-C15 : 0 (10.4 %). The genomic DNA G+C content of 1_25T was 69 mol %. The results of phylogenetic analysis based on 16S rRNA gene sequence indicated that 1_25T had high sequence similarity with Streptomyces qinglanensis 172205T (98.1 %), Streptomyces lycii TRM 66187T (98 %), and Streptomyces griseocarneus JCM4580T (98 %). In addition to the differences in phenotypic characters, the average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between 1_25T and closely related species were below the recommended threshold values for assigning strains to the same species. The fermentation product of 1_25T in ISP2 had an inhibitory effect on Staphylococcus aureus. On the basis of these genotypic and phenotypic characteristics, strain 1_25T (=JCM 34936T=GDMCC 4.216T) represents a novel species of the genus Streptomyces, for which the name Streptomyces gobiensis sp. nov. is proposed.