Heterotrophic nitrification by Alcaligenes faecalis links organic and inorganic nitrogen metabolism.

Heterotrophic nitrification remains a mystery for decades. It has been commonly hypothesized that heterotrophic nitrifiers oxidize ammonia to hydroxylamine and then to nitrite in a way similar to autotrophic AOA and AOB. Recently, heterotrophic nitrifiers from Alcaligenes were found to oxidize ammonia to hydroxylamine and then to N2 ("dirammox", direct ammonia oxidation) by the gene cluster dnfABC with a yet-to-be-reported mechanism. The role of a potential glutamine amidotransferase DnfC clues the heterotrophic ammonia oxidation might involving in glutamine. Here, we found Alcaligenes faecalis JQ135 could oxidize amino acids besides ammonia. We discovered that glutamine is an intermediate of the dirammox pathway and the glutamine synthetase gene is essential for both A. faecalis JQ135 and the E. coli cells harboring dnfABC gene cluster to oxidize amino acids and ammonia. Our study expands understanding of heterotrophic nitrifiers and challenges the classical paradigm of heterotrophic nitrification.

Deep insights into the assembly mechanisms, co-occurrence patterns, and functional roles of microbial community in wastewater treatment plants.

The understanding of activated sludge microbial status and roles is imperative for improving and enhancing the performance of wastewater treatment plants (WWTPs). In this study, we conducted a deep analysis of activated sludge microbial communities across five compartments (inflow, effluent, and aerobic, anoxic, anaerobic tanks) over temporal scales, employing high-throughput sequencing of 16S rRNA amplicons and metagenome data. Clearly discernible seasonal patterns, exhibiting cyclic variations, were observed in microbial diversity, assembly, co-occurrence network, and metabolic functions. Notably, summer samples exhibited higher α-diversity and were distinctly separated from winter samples. Our analysis revealed that microbial community assembly is influenced by both stochastic processes (66%) and deterministic processes (34%), with winter samples demonstrating more random assembly compared to summer. Co-occurrence patterns were predominantly mutualistic, with over 96% positive correlations, and summer networks were more organized than those in winter. These variations were significantly correlated with temperature, total phosphorus and sludge volume index. However, no significant differences were found among microbial community across five compartments in terms of ß diversity. A core community of keystone taxa was identified, playing key roles in eight nitrogen and eleven phosphorus cycling pathways. Understanding the assembly mechanisms, co-occurrence patterns, and functional roles of microbial communities is essential for the design and optimization of biotechnological treatment processes in WWTPs.

The gapless genome assembly and multi-omics analyses unveil a pivotal regulatory mechanism of oil biosynthesis in the olive tree.

Olive is a valuable oil-bearing tree with fruits containing high levels of fatty acids. Oil production is a multifaceted process involving intricate interactions between fatty acid biosynthesis and other metabolic pathways that are affected by genetics and the developmental stages of the fruit. However, a comprehensive understanding of the underlying regulatory mechanisms is still lacking. Here, we generated a gap-free telomere-to-telomere assembly for Olea europaea cv. 'Leccino', representing an olive genome with the highest contiguity and completeness to date. The combination of time-course metabolomics and transcriptomics datasets revealed a negative correlation between fatty acid and flavonoid biosynthesis in the initial phase of olive fruit development, which was subject to an opposing regulatory mechanism mediated by the hub transcription factor MYC2. Multifaceted molecular assays demonstrated that MYC2 is a repressor of fatty acid biosynthesis by downregulating the expression of BCCP2 (biotin carboxylase carrier protein 2), while it acts as an activator of FLS (flavonol synthase), leading to an increase in flavonoid synthesis. Furthermore, the expression of MYC2 is regulated by fluctuations of methyl jasmonate content during olive fruit development. Our study completes a high-quality gapless genome of an olive cultivar, and provides new insight into the regulatory mechanisms underlying the biosynthesis of fatty acids and flavonoids in its fruit.

Comparative transcriptome provides new insights into the molecular regulation of olive trees to chilling stress.

Olive (Olea europaea L.), an economically important oil-producing crop, is sensitive to low temperature, which severely limits its productivity and geographical distribution. However, the underlying mechanism of cold tolerance in olive remains elusive. In this study, a chilling experiment (4 °C) on the living saplings of two olive cultivars revealed that O. europaea cv. Arbequina showed stronger cold tolerance with greater photosynthetic activity compared with O. europaea cv. Leccino. Transcriptome analyses revealed that early light-inducible protein 1 (ELIP1), the main regulator for chlorophyll synthesis, is dramatically induced to protect the photosynthesis at low temperatures. Furthermore, weighted gene co-expression network analysis, yeast one-hybrid and luciferase assays demonstrated that transcription factor bHLH66 serves as an important regulator of ELIP1 transcription by binding to the G-box motif in the promoter. Taken together, our research revealed a novel transcriptional module consisting of bHLH66-ELIP1 in the adaptation of olive trees to cold stress.

Sphingobium sp. SJ10-10 encodes a not-yet-reported chromate reductase and the classical Rieske dioxygenases to simultaneously degrade PAH and reduce chromate.

Both polycyclic aromatic hydrocarbons (PAHs) and heavy metals persist in the environment and are toxic to organisms. Their co-occurrence makes any of them difficult to remove during bioremediation and poses challenges to environmental management and public health. Microorganisms capable of effectively degrading PAHs and detoxifying heavy metals concurrently are required to improve the bioremediation process. In this study, we isolated a new strain, Sphingobium sp. SJ10-10, from an abandoned coking plant and demonstrated its capability to simultaneously degrade 92.6 % of 75 mg/L phenanthrene and reduce 90 % of 3.5 mg/L hexavalent chromium [Cr(VI)] within 1.5 days. Strain SJ10-10 encodes Rieske non-heme iron ring-hydroxylating oxygenases (RHOs) to initiate PAH degradation. Additionally, a not-yet-reported protein referred to as Sphingobium chromate reductase (SchR), with low sequence identity to known chromate reductases, was identified to reduce Cr(VI). SchR is distributed across different genera and can be classified into two classes: one from Sphingobium members and the other from non-Sphingobium species. The widespread presence of SchR in those RHO-containing Sphingobium members suggests that they are excellent candidates for bioremediation. In summary, our study demonstrates the simultaneous removal of PAHs and Cr(VI) by strain SJ10-10 and provides valuable insights into microbial strategies for managing complex pollutant mixtures.

SLC7A2-Mediated Lysine Catabolism Inhibits Immunosuppression in Triple Negative Breast Cancer.

Breast cancer is one of the most common malignant tumors worldwide. SLC7A2 is abnormally expressed in multiple cancers. However, its potential in triple negative breast cancer (TNBC) is still unclear. The purpose of this study was to investigate the roles of SLC7A2 and its underlying molecular mechanisms in TNBC. mRNA expression was detected by RT-qPCR. Protein expression was detected by western blot. Co-localization of ACOX1 and TCF1 was determined using FISH assay. Histone crotonylation was performed using in vitro histone crotonylation assay. Functional analysis was performed using CCK-8 and flow cytometry assays. Xenograft assay was conducted to further verify the role of SLC7A2 in TNBC. CD8A expression was detected using immunohistochemistry. We found that SLC7A2 is downregulated in TNBC tumors. Low levels are associated with advanced stages and lymph node metastasis. SLC7A2 expression is positively correlated with CD8A. SLC7A2-mediated lysine catabolism drives the activation of CD8+ T cells. Moreover, SLC7A2 promotes histone crotonylation via upregulating ACOX1. It also promotes interaction between ACOX1 and TCF1, thus promoting antitumor T cell immunity. Additionally, overexpression of SLC7A2 activates CD8+ T cells and enhances the chemosensitivity of anti-PD-1 therapies in vivo. In conclusion, SLC7A2 may function as an antitumor gene in TNBC by activating antitumor immunity, suggesting SLC7A2/ACOX1/TCF1 signaling as a promising therapeutic strategy.

Fodinisporobacter ferrooxydans gen. nov., sp. nov.-A Spore-Forming Ferrous-Oxidizing Bacterium Isolated from a Polymetallic Mine.

A novel acidophilic, aerobic bacterium strain, MYW30-H2T, was isolated from a heap of polymetallic mine. Cells of strain MYW30-H2T were Gram-stain-positive, endospore-forming, motile, and rod-shaped. Strain MYW30-H2T grew at a temperature range of 30-45 °C (optimum 40 °C) and a pH range of 3.5-6.0 (optimum 4.0) in the presence of 0-0.5% (w/v) NaCl. Strain MYW30-H2T could grow heterotrophically on yeast extract and glucose, and grow mixotrophically using ferrous iron as an electron donor with yeast extract. Menaquinone-7 (MK-7) was the sole respiratory quinone of the strain. Iso-C15:0 and anteiso-C15:0 were the major cellular fatty acids. The 16S rRNA gene sequence analysis showed that MYW30-H2T was phylogenetically affiliated with the family Alicyclobacillaceae, and the sequence similarity with other Alicyclobacillaceae genera species was below 91.51%. The average amino acid identity value of the strain with its phylogenetically related species was 52.3-62.1%, which fell into the genus boundary range. The DNA G+C content of the strain was 44.2%. Based on physiological and phylogenetic analyses, strain MYW30-H2T represents a novel species of a new genus of the family Alicyclobacillaceae, for which the name Fodinisporobacter ferrooxydans gen. nov., sp. nov. is proposed. The type strain is MYW30-H2T (=CGMCC 1.17422T = KCTC 43278T).

Acidithiobacillus acidisediminis sp. nov., an acidophilic sulphur-oxidizing chemolithotroph isolated from acid mine drainage sediment.

Strain S30A2T, isolated from the acid mine drainage sediment of Mengzi Copper Mine, Yunnan, is proposed to represent a novel species of the sulphur-oxidizing genus Acidithiobacillus. Cells were Gram-stain-negative, non-endospore forming, highly motile with one or two monopolar flagella and rod-shaped. The strain was mesophilic, growing at 30-50 °C (optimum, 38 °C), acidophilic, growing at pH 2.0-4.5 (optimum, pH 2.5), and tolerant of 0-4 % (w/v; 684 mol l-1) NaCl. The 16S rRNA gene-based sequence analysis showed that strain S30A2T belongs to the genus Acidithiobacillus and shows the largest similarity of 96.6 % to the type strain Acidithiobacillus caldus KUT. The genomic DNA G+C content of strain S30A2T was 59.25 mol%. The average nucleotide identity ANIb and ANIm values between strain S30A2T and A. caldus KUT were 70.95 and 89.78 %, respectively and the digital DNA-DNA hybridization value was 24.9 %. Strain S30A2T was strictly aerobic and could utilize elementary sulphur and tetrathionate to support chemolithotrophic growth. The major cellular fatty acid of S30A2T was C19 : 1ω7c. The respiratory quinones were ubiquinone-8 and ubiquinone-7. Based upon its phylogenetic, genetic, phenotypic, physiologic and chemotaxonomic characteristics, strain S30A2T is considered to represent a novel species of the genus Acidithiobacillus, for which the name Acidithiobacillus acidisediminis sp. nov. is proposed. The type strain is S30A2T (=CGMCC 1.17059T=KCTC 72580T).

Xiashengella succiniciproducens gen. nov., sp. nov., a succinate-producing bacterium isolated from an anaerobic digestion tank in the family Marinilabiliaceae of the order Bacteroidales.

A strictly anaerobic, motile bacterium, designated as strain Ai-910T, was isolated from the sludge of an anaerobic digestion tank in China. Cells were Gram-stain-negative rods. Optimal growth was observed at 38 °C (growth range 25-42 °C), pH 8.5 (growth range 5.5-10.5), and under a NaCl concentration of 0.06% (w/v) (range 0-2.0%). Major cellular fatty acids were iso-C15 : 0 and anteiso-C15 : 0. The respiratory quinone was MK-7. Using xylose as the growth substrate, succinate was produced as the fermentation product. Phylogenetic analysis based on the 16 S rRNA gene sequences indicated that strain Ai-910T formed a distinct phylogenetic lineage that reflects a new genus in the family Marinilabiliaceae, sharing high similarities to Alkaliflexus imshenetskii Z-7010T (92.78%), Alkalitalea saponilacus SC/BZ-SP2T (92.51%), and Geofilum rubicundum JAM-BA0501T (92.36%). Genomic similarity (average nucleotide identity and digital DNA-DNA hybridization) values between strain Ai-910T and its phylogenetic neighbors were below 65.27 and 16.90%, respectively, indicating that strain Ai-910T represented a novel species. The average amino acid identity between strain Ai-910T and other related members of the family Marinilabiliaceae were below 69.41%, supporting that strain Ai-910T was a member of a new genus within the family Marinilabiliaceae. Phylogenetic, genomic, and phenotypic analysis revealed that strain Ai-910T was distinguished from other phylogenetic relatives within the family Marinilabiliaceae. The genome size was 3.10 Mbp, and the DNA G + C content of the isolate was 42.8 mol%. Collectively, differences of the phenotypic and phylogenetic features of strain Ai-910T from its close relatives suggest that strain Ai-910T represented a novel species in a new genus of the family Marinilabiliaceae, for which the name Xiashengella succiniciproducens gen. nov., sp. nov. was proposed. The type strain of Xiashengella succiniciproducens is Ai-910T (= CGMCC 1.17893T = KCTC 25,304T).

The SOX2/PDIA6 axis mediates aerobic glycolysis to promote stemness in non-small cell lung cancer cells.

Non-small cell lung cancer (NSCLC) is an aggressive and rapidly expanding lung cancer. Abnormal upregulation or knockdown of PDIA6 expression can predict poor prognosis in various cancers. This study aimed to investigate the biological function of PDIA6 in NSCLC. SOX2 and PDIA6 expression in NSCLC tissues and regulatory relationship between them were analyzed using bioinformatics. GSEA was performed on the enrichment pathway of PDIA6. qRT-PCR was utilized to examine expression of SOX2 and PDIA6 in NSCLC tissues and cells, and dual-luciferase reporter assay and ChIP experiments were performed to validate their regulatory relationship. CCK-8 experiment was conducted to assess cell viability, western blot was to examine levels of stem cell markers and proteins related to aerobic glycolysis pathway in cells. Cell sphere formation assay was used to evaluate efficiency of cell sphere formation. Reagent kits were used to measure glycolysis levels and glycolysis products. High expression of PDIA6 in NSCLC was linked to aerobic glycolysis. Knockdown of PDIA6 reduced cell viability, expression of stem cell surface markers, and cell sphere formation efficiency in NSCLC. Overexpression of PDIA6 could enhance cell viability and promote aerobic glycolysis, but the addition of 2-DG could reverse this result. Bioinformatics predicted the existence of upstream transcription factor SOX2 for PDIA6, and SOX2 was significantly upregulated in NSCLC, and they had a binding relationship. Further experiments revealed that PDIA6 overexpression restored repressive effect of knocking down SOX2 on aerobic glycolysis and cell stemness. This work revealed that the SOX2/PDIA6 axis mediated aerobic glycolysis to promote NSCLC cell stemness, providing new therapeutic strategies for NSCLC.

Fungal communities as dual indicators of river biodiversity and water quality assessment.

Given their ecological importance, bioindicators are used for the assessment of the health of river ecosystems. This study explored the fungal compositions and the potential of fungal taxa as bioindicators for indicating the water quality of the Mekong River, as the use of fungal indicators of the Mekong River was not previously well characterized. The Mekong River exhibited dynamic variations in both physicochemical/hydrochemical properties and fungal communities according to seasons and locations. The results revealed the dominance of alkaline earth metal ions and weak acids in the water. The magnesium-bicarbonate water type was found in the dry season, but the water became the chloride-calcium type or mixed type of magnesium-bicarbonate and chloride-calcium in the rainy season at downstream sites. Fungal composition analysis revealed the dominance of Chytridiomycota in the dry season and intermediate periods, and Ascomycota and Basidiomycota in the rainy season. The fungal communities were influenced by stochastic and deterministic assembly processes, mainly homogeneous selection, heterogeneous selection, and dispersal limitation. The extent of environmental filtering implied that some fungal taxa were affected by environmental conditions, suggesting the possibility of identifying certain fungal taxa suitable for being bioindicators of water quality. Subsequently, machine learning with recursive feature elimination identified specific fungal bins mostly consisting of Agaricomycetes (mainly Polyporales, Agaricales, and Auriculariales), Dothideomycetes (mainly Pleosporales), Saccharomycetes (mainly Saccharomycetales), Chytridiomycota, and Rozellomycota as bioindicators that could predict ambient and irrigation water quality with high selectivity and sensitivity. These results thus promote the use of fungal indicators to assess the health of the river.

Microbiome-functionality in anaerobic digesters: A critical review.

Microbially driven anaerobic digestion (AD) processes are of immense interest due to their role in the biovalorization of biowastes into renewable energy resources. The function-versatile microbiome, interspecies syntrophic interactions, and trophic-level metabolic pathways are important microbial components of AD. However, the lack of a comprehensive understanding of the process hampers efforts to improve AD efficiency. This study presents a holistic review of research on the microbial and metabolic "black box" of AD processes. Recent research on microbiology, functional traits, and metabolic pathways in AD, as well as the responses of functional microbiota and metabolic capabilities to optimization strategies are reviewed. The diverse ecophysiological traits and cooperation/competition interactions of the functional guilds and the biomanipulation of microbial ecology to generate valuable products other than methane during AD are outlined. The results show that AD communities prioritize cooperation to improve functional redundancy, and the dominance of specific microbes can be explained by thermodynamics, resource allocation models, and metabolic division of labor during cross-feeding. In addition, the multi-omics approaches used to decipher the ecological principles of AD consortia are summarized in detail. Lastly, future microbial research and engineering applications of AD are proposed. This review presents an in-depth understanding of microbiome-functionality mechanisms of AD and provides critical guidance for the directional and efficient bioconversion of biowastes into methane and other valuable products.

Attractant and repellent induce opposing changes in the four-helix bundle ligand-binding domain of a bacterial chemoreceptor.

Motile bacteria navigate toward favorable conditions and away from unfavorable environments using chemotaxis. Mechanisms of sensing attractants are well understood; however, molecular aspects of how bacteria sense repellents have not been established. Here, we identified malate as a repellent recognized by the MCP2201 chemoreceptor in a bacterium Comamonas testosteroni and showed that it binds to the same site as an attractant citrate. Binding determinants for a repellent and an attractant had only minor differences, and a single amino acid substitution in the binding site inverted the response to malate from a repellent to an attractant. We found that malate and citrate affect the oligomerization state of the ligand-binding domain in opposing way. We also observed opposing effects of repellent and attractant binding on the orientation of an alpha helix connecting the sensory domain to the transmembrane helix. We propose a model to illustrate how positive and negative signals might be generated.

Antioxidant Capacity of Free and Bound Phenolics from Olive Leaves: In Vitro and In Vivo Responses.

Olive leaves are rich in phenolic compounds. This study explored the chemical profiles and contents of free phenolics (FPs) and bound phenolics (BPs) in olive leaves, and further investigated and compared the antioxidant properties of FPs and BPs using chemical assays, cellular antioxidant evaluation systems, and in vivo mouse models. The results showed that FPs and BPs have different phenolic profiles; 24 free and 14 bound phenolics were identified in FPs and BPs, respectively. Higher levels of phenolic acid (i.e., sinapinic acid, 4-coumaric acid, ferulic acid, and caffeic acid) and hydroxytyrosol were detected in the BPs, while flavonoids, triterpenoid acids, and iridoids were more concentrated in the free form. FPs showed a significantly higher total flavonoid content (TFC), total phenolic content (TPC), and chemical antioxidant properties than those of BPs (p < 0.05). Within the range of doses (20-250 µg/mL), both FPs and BPs protected HepG2 cells from H2O2-induced oxidative stress injury, and there was no significant difference in cellular antioxidant activity between FPs and BPs. The in vivo experiments suggested that FP and BP treatment inhibited malondialdehyde (MDA) levels in a D-galactose-induced oxidation model in mice, and significantly increased antioxidant enzyme activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and the total antioxidant capacity (T-AOC). Mechanistically, FPs and BPs exert their antioxidant activity in distinct ways; FPs ameliorated D-galactose-induced oxidative stress injury partly via the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway, while the BP mechanisms need further study.

Sequence similarity network and protein structure prediction offer insights into the evolution of microbial pathways for ferrous iron oxidation.

IMPORTANCE: Microbial Fe(II) oxidation is a crucial process that harnesses and converts the energy available in Fe, contributing significantly to global element cycling. However, there are still many aspects of this process that remain unexplored. In this study, we utilized a combination of comparative genomics, sequence similarity network analysis, and artificial intelligence-driven structure modeling methods to address the lack of structural information on Fe(II) oxidation proteins and offer a comprehensive perspective on the evolution of Fe(II) oxidation pathways. Our findings suggest that several microbial Fe(II) oxidation pathways currently known may have originated within classes Gammaproteobacteria and Betaproteobacteria.

AI-driven pan-proteome analyses reveal insights into the biohydrometallurgical properties of Acidithiobacillia.

Microorganism-mediated biohydrometallurgy, a sustainable approach for metal recovery from ores, relies on the metabolic activity of acidophilic bacteria. Acidithiobacillia with sulfur/iron-oxidizing capacities are extensively studied and applied in biohydrometallurgy-related processes. However, only 14 distinct proteins from Acidithiobacillia have experimentally determined structures currently available. This significantly hampers in-depth investigations of Acidithiobacillia's structure-based biological mechanisms pertaining to its relevant biohydrometallurgical processes. To address this issue, we employed a state-of-the-art artificial intelligence (AI)-driven approach, with a median model confidence of 0.80, to perform high-quality full-chain structure predictions on the pan-proteome (10,458 proteins) of the type strain Acidithiobacillia. Additionally, we conducted various case studies on de novo protein structural prediction, including sulfate transporter and iron oxidase, to demonstrate how accurate structure predictions and gene co-occurrence networks can contribute to the development of mechanistic insights and hypotheses regarding sulfur and iron utilization proteins. Furthermore, for the unannotated proteins that constitute 35.8% of the Acidithiobacillia proteome, we employed the deep-learning algorithm DeepFRI to make structure-based functional predictions. As a result, we successfully obtained gene ontology (GO) terms for 93.6% of these previously unknown proteins. This study has a significant impact on improving protein structure and function predictions, as well as developing state-of-the-art techniques for high-throughput analysis of large proteomic data.

Comparative genomics reveals extensive intra-species genetic divergence of the prevalent gut commensal Ruminococcus gnavus.

Ruminococcus gnavus is prevalent in the intestines of humans and animals, and ambiguities have been reported regarding its relations with the development of diseases and host well-being. We postulate the ambiguities of its function in different cases may be attributed to strain-level variability of genomic features of R. gnavus. We performed comparative genomic and pathogenicity prediction analysis on 152 filtered high-quality genomes, including 4 genomes of strains isolated from healthy adults in this study. The mean G+C content of genomes of R. gnavus was 42.73±0.33 mol%, and the mean genome size was 3.46±0.34 Mbp. Genome-wide evolutionary analysis revealed R. gnavus genomes were divided into three major phylogenetic clusters. Pan-core genome analysis revealed that there was a total of 28 072 predicted genes, and the core genes, soft-core genes, shell genes and cloud genes accounted for 3.74 % (1051/28 072), 1.75 % (491/28 072), 9.88 % (2774/28 072) and 84.63 % (23 756/28 072) of the total genes, respectively. The small proportion of core genes reflected the wide divergence among R. gnavus strains. We found certain coding sequences with determined health benefits (such as vitamin production and arsenic detoxification), whilst some had an implication of health adversity (such as sulfide dehydrogenase subunits). The functions of the majority of core genes were unknown. The most widespread genes functioning in antibiotic resistance and virulence are tetO (tetracycline-resistance gene, present in 75 strains) and cps4J (capsular polysaccharide biosynthesis protein Cps4J encoding gene, detected in 3 genomes), respectively. Our results revealed genomic divergence and the existence of certain safety-relevant factors of R. gnavus. This study provides new insights for understanding the genomic features and health relevance of R. gnavus, and raises concerns regarding predicted prevalent pathogenicity and antibiotic resistance among most of the strains.

Diagnostic value of alkaline phosphatase and bone-specific alkaline phosphatase for metastases in breast cancer: a systematic review and meta-analysis.

PURPOSE: Numerous studies had reported the diagnostic value of alkaline phosphatase (ALP) and its bone-specific isoforms (BAP) in the metastases of breast cancer (BC). The purpose of this meta-analysis was to summarize the diagnostic value of serum ALP and BAP in metastatic BC, especially focused on bone metastases. METHODS: We searched comprehensively in the PubMed, Cochrane Library, and EMBASE for studies to explore the diagnostic accuracy of serum ALP/BAP level for metastatic BC. Qualities of including studies were assessed and pooled sensitivity, specificity, and summary receiver operating characteristic curve were calculated. Publication bias was assessed and meta-regression was conducted. RESULTS: We finally included 25 studies with a total of 12,155 BC patients (1681 metastatic cases and 10,474 controls). According to the QUADAS-2 tool to assessment the methodological quality, most of the included studies were judged as high risk of patient selection bias. High serum levels of ALP/BAP in bone metastatic BC patients could be found compared with non-metastatic BC patients. The pooled sensitivity and specificity of ALP for BC bone metastases were 0.62 and 0.86, and the area under the curve (AUC) was 0.80. The pooled sensitivity and specificity of ALP for all site metastases (mainly bone and liver) were 0.56 and 0.91, and the AUC was 0.90. The pooled sensitivity and specificity of BAP for BC bone metastases were 0.66 and 0.92, and the AUC was 0.89. CONCLUSION: Although not promising, serum ALP and BAP could bring useful information for the early detection of BC metastases especially for the bone metastases.

The sulfonamide-resistance dihydropteroate synthase gene is crucial for efficient biodegradation of sulfamethoxazole by Paenarthrobacter species.

Sulfonamide antibiotics (SAs) are serious pollutants to ecosystems and environments. Previous studies showed that microbial degradation of SAs such as sulfamethoxazole (SMX) proceeds via a sad-encoded oxidative pathway, while the sulfonamide-resistant dihydropteroate synthase gene, sul, is responsible for SA resistance. However, the co-occurrence of sad and sul genes, as well as how the sul gene affects SMX degradation, was not explored. In this study, two SMX-degrading bacterial strains, SD-1 and SD-2, were cultivated from an SMX-degrading enrichment. Both strains were Paenarthrobacter species and were phylogenetically identical; however, they showed different SMX degradation activities. Specifically, strain SD-1 utilized SMX as the sole carbon and energy source for growth and was a highly efficient SMX degrader, while SD-2 did could not use SMX as a sole carbon or energy source and showed limited SMX degradation when an additional carbon source was supplied. Genome annotation, growth, enzymatic activity tests, and metabolite detection revealed that strains SD-1 and SD-2 shared a sad-encoded oxidative pathway for SMX degradation and a pathway of protocatechuate degradation. A new sulfonamide-resistant dihydropteroate synthase gene, sul918, was identified in strain SD-1, but not in SD-2. Moreover, the lack of sul918 resulted in low SMX degradation activity in strain SD-2. Genome data mining revealed the co-occurrence of sad and sul genes in efficient SMX-degrading Paenarthrobacter strains. We propose that the co-occurrence of sulfonamide-resistant dihydropteroate synthase and sad genes is crucial for efficient SMX biodegradation. KEY POINTS: • Two sulfamethoxazole-degrading strains with distinct degrading activity, Paenarthrobacter sp. SD-1 and Paenarthrobacter sp. SD-2, were isolated and identified. • Strains SD-1 and SD-2 shared a sad-encoded oxidative pathway for SMX degradation. • A new plasmid-borne SMX resistance gene (sul918) of strain SD-1 plays a crucial role in SMX degradation efficiency.

Gut microbiota and intestinal barrier function in subjects with cognitive impairments: a cross-sectional study.

Background: Gut-brain axis might play an important role in cognitive impairments by various diseases including Alzheimer's disease (AD). Objective: To investigate the differences in gut microbial composition, intestinal barrier function, and systemic inflammation in patients with AD or mild cognitive impairment (MCI), and normal control (NC) cases. Methods: A total of 118 subjects (45 AD, 38 MCI, and 35 NC) were recruited. Cognitive function was assessed using Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment Scale (MoCA). Functional ability was assessed using Activity of Daily Living Scale (ADL). The composition of gut microbiome was examined by 16S rRNA high-throughput sequencing. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict functional transfer of gut microbiota. Gut barrier dysfunction was evaluated by measuring the levels of diamine oxidase (DAO), D-lactic acid (DA), and endotoxin (ET). The serum high-sensitivity C-reactive protein (hs-CRP) level was used to indicate systemic inflammation. Results: Compared with normal controls, patients with cognitive impairments (AD and MCI) had lower abundance of Dorea and higher levels of DAO, DA, and ET. Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that the pathways related to glycan biosynthesis and metabolism increased in MCI patients, while the ones related to membrane transport decreased. The abundance of Bacteroides and Faecalibacterium was negatively correlated with the content of ET, and positively correlated with the scores of MMSE and MoCA. The hs-CRP levels were similar among the three groups. A significant negative correlation was observed between the severity of gut barrier dysfunction and cognitive function. Conclusion: Cognitive impairments might be associated with gut microbial dysbiosis and intestinal barrier dysfunction.