SIMBA: single-cell embedding along with features.

Most current single-cell analysis pipelines are limited to cell embeddings and rely heavily on clustering, while lacking the ability to explicitly model interactions between different feature types. Furthermore, these methods are tailored to specific tasks, as distinct single-cell problems are formulated differently. To address these shortcomings, here we present SIMBA, a graph embedding method that jointly embeds single cells and their defining features, such as genes, chromatin-accessible regions and DNA sequences, into a common latent space. By leveraging the co-embedding of cells and features, SIMBA allows for the study of cellular heterogeneity, clustering-free marker discovery, gene regulation inference, batch effect removal and omics data integration. We show that SIMBA provides a single framework that allows diverse single-cell problems to be formulated in a unified way and thus simplifies the development of new analyses and extension to new single-cell modalities. SIMBA is implemented as a comprehensive Python library ( https://simba-bio.readthedocs.io ).

A pneumonia outbreak associated with a new coronavirus of probable bat origin.

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats1-4. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans5-7. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.

Bibliometric analysis of childhood-onset systemic lupus erythematosus from 2000 to 2022.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disorder. When SLE occurs in individuals under the age of 18, it is referred to as childhood-onset SLE (cSLE). Currently, there is a dearth of bibliometric research pertaining to cSLE. METHOD: Relevant studies in the field of cSLE from 2000 to 2022 were screened from the Web of Science Core Collection (WoSCC). CiteSpace and VOSviewer software were used to visualize the annual publications, countries, institutions, authors, journals, keywords, and references, after which the authors conducted the scientific analysis. RESULTS: A total of 2857 articles were included in this study, and the number of articles published in the past 20 years showed an overall upwards trend. The most prolific countries are the United States, China, and Brazil; however, the United States, Canada, and the United Kingdom are clearly superior in terms of literary influence, and there is more cooperation between them and their institutions. LUPUS (n = 389) contributed the most to the variance. Brunner, HI's contribution in the field of cSLE is outstanding. The words related to 'lupus nephritis' and 'antibodies' are important words reflected in the keyword network diagram. The keywords included 'evidence-based recommendation', 'validation', 'diagnosis' and 'adult' from 2019, and 'continuous bursts' to the present. CONCLUSION: This study examined the research status of cSLE patients, discussed and analysed the research hotspots and trends in this field, and provided a reference for further research in this field to promote the development of cSLE research.

Bibliometric and altmetric analyses of publication activity in the field of idiopathic inflammatory myopathy in 2011-2021 based on web of science core collection databases.

Idiopathic inflammatory myopathy is a multisystem autoimmune condition characterized by muscle inflammation (myositis) and interstitial lung disease (ILD). Bibliometric analysis and altmetric analysis are effective methods of evaluating academic productivity and measuring the influence of publications. The purpose of this study is to analyze the research productivity and influence of idiopathic inflammatory myopathy articles using bibliometric analysis and altmetric analysis. Data from articles published between 2011 and 2021 were obtained from the Web of Science. Altmetric attention scores and Mendeley reader counts of the articles were obtained from altmetric evaluations. In the study, 2060 articles related to idiopathic inflammatory myopathy were screened out showing an increasing trend in general. In terms of the origin countries of articles, the United States (n = 467, 22.67%) ranked first. Johns Hopkins University has the largest number of institutions (n = 113). The journals regarding idiopathic inflammatory myopathy and Rheumatology (n = 87) published the most articles. The most cited article was published by Mammen et al. and was related to autoantibodies. Dermatomyositis, polymyositis and other research hotspots were represented by keywords. The results of the altmetric analysis showed that citations, impact factors and h-index were significantly correlated with Altmetric Attention Scores and Mendeley Readers Count (P < 0.05). In summary, bibliometric analysis summarizes the current status of idiopathic inflammatory myopathy research and helps to understand the development of idiopathic inflammatory myopathy in the field between 2011 and 2021. Altmetric analysis was used to evaluate the academic and social influence of articles from the novel perspective of internet attention.

The Microbiota of Human Lung of Pulmonary Tuberculosis and the Alteration Caused by Anti-tuberculosis Drugs.

An in-depth understanding of the lung microbiota in tuberculosis (TB) infection could provide optimal strategies for the prophylaxis, diagnosis, and treatment of the disease. Only a few studies have investigated the impact of Mycobacterium tuberculosis (Mtb) infection and anti-TB treatment on the lung microbiota. Bronchoalveolar lavage fluid and blood samples were collected from 23 active TB patients (TBZ), 17 latent tuberculosis infection patients (LTBI), 13 healthy controls (HC), and 14 active TB patients with 1-month anti-TB therapy (TBM) for 16S RNA sequencing and serological indexes, respectively. Low body mass index, albumin, and total triglyceride levels were detected in TBZ. Pulmonary Mtb infection led to a minor decrease in the alpha diversity of the lung microbiota in TBZ than HC, but a significant difference was noted in beta diversity. Subsequently, anti-TB therapy caused a rapid alteration in the lung community structure due to reduced alpha and beta diversity. Proteobacteria were abundant in TBZ samples, while Firmicutes was predominant in the LITB and HC samples. Lactobacillus and Subdoligranulum (genera) were the most unique in the LTBI and HC group, respectively. The TBM group showed the most predominant abundance of Bacteroides, Oscillospira, and Ruminococcus (genera). Functional pathways, such as indole alkaloid biosynthesis, Wnt signaling pathway, endocytosis, and metabolism of xenobiotics by cytochrome P450, significantly decreased in the TBM group compared with TBZ group. Pulmonary TB and anti-TB treatment caused a distinct dysbiosis of the lung microbiome. The current findings suggested potential links between the lung microbiota and TB onset, progression, and treatment.

LINC00665 induces gastric cancer progression through activating Wnt signaling pathway.

Long noncoding RNAs (lncRNAs) are recently recognized as noteworthy regulators of different tumors, counting gastric cancer (GC). Lately, long intergenic noncoding RNA (LINC) 00665 has been verified to display significant parts in several cancers. Be that as it may, its role and mechanism in GC movement still stay uninvestigated. As of now, we observed LINC00665 was obviously GC cells (MKN28, BGC-823, SGC7-901, AGS, HGC-27) in comparison to GES-1 cells, which was identified as human normal gastric epithelial cells. Then, LINC00665 was obviously downregulated in GC cells including AGS and BGC-823 cells. Loss of LINC00665 greatly repressed AGS and BGC-823 cell survival and cell expansion. Moreover, GC cell apoptosis was significantly induced by the loss of LINC00665. For another, we found that the GC cell cycle was also captured in G1 and G2 phases. The experiments on cell migration and invasion indicated that knockdown of LINC00665 restrained GC cell migration and invasion. Modifications in Wnt signaling are closely associated with the development of cancers. Here, we found that Wnt signaling was significantly inactivated by the silence of LINC00665 in GC cells. ß-catenin and cyclinD1 were restrained whereas GSK-3ß was induced by the inhibition of LINC00665 in GC cells. Furthermore, we confirmed the impact of LINC00665 in vivo using xenograft models. Taken these together, we indicated that LINC00665 could function as a novel biomarker in GC progression.

Robust and Scalable Learning of Complex Intrinsic Dataset Geometry via ElPiGraph.

Multidimensional datapoint clouds representing large datasets are frequently characterized by non-trivial low-dimensional geometry and topology which can be recovered by unsupervised machine learning approaches, in particular, by principal graphs. Principal graphs approximate the multivariate data by a graph injected into the data space with some constraints imposed on the node mapping. Here we present ElPiGraph, a scalable and robust method for constructing principal graphs. ElPiGraph exploits and further develops the concept of elastic energy, the topological graph grammar approach, and a gradient descent-like optimization of the graph topology. The method is able to withstand high levels of noise and is capable of approximating data point clouds via principal graph ensembles. This strategy can be used to estimate the statistical significance of complex data features and to summarize them into a single consensus principal graph. ElPiGraph deals efficiently with large datasets in various fields such as biology, where it can be used for example with single-cell transcriptomic or epigenomic datasets to infer gene expression dynamics and recover differentiation landscapes.

Simultaneous acetone-butanol-ethanol fermentation, gas stripping, and full-cell-catalyzed esterification for effective production of butyl oleate.

In this study, aiming to improve the economic feasibility of acetone-butanol-ethanol (ABE) fermentation process, generate valuable products and extend the product chain, esterification catalyzed by Candida sp. 99-125 cells was hybrid with the ABE fermentation-gas-stripping integration system. The gas-stripping condensate that contained concentrated ABE products was directly used for esterification without the participation of toxic organic solvents. Full-cell catalysis temperature and the cell dosage rate on oleate production were evaluated and optimized in the esterification process. Under the optimized conditions (35 °C, 8% of cells), ~ 68% of butyl oleate and ~ 12% of ethyl oleate were obtained after 4 h of esterification. The Candida sp. 99-125 cells were able to be reused for at least four cycles. The novel cascade process showed environmental benefits, which also showed promising in improving the economic feasibility of the conventional ABE fermentation process.

Bibliometric analysis of global literature productivity in systemic lupus erythematosus from 2013 to 2022.

BACKGROUND: Bibliometric analysis is a mature method for quantitative evaluation of academic productivity. In view of the rapid development of research in the field of systemic lupus erythematosus (SLE) in the past decade, we used bibliometric methods to comprehensively analyze the literature in the field of SLE from 2013 to 2022. METHODS: The relevant literature in the field of SLE from 2013 to 2022 was screened in the Web of Science Core Collection database. After obtaining and sorting out the data, CiteSpace and VOSviewer software were used to visualize the relevant data, and SPSS software was used for scientific statistics. RESULTS: A total of 18,450 publications were included in this study. The number of articles published over the past 10 years has generally shown an upward trend, while Altmetric attention scores have also shown a clear upward trend in general and in most countries. Citation analysis and Altmetric analysis can mutually prove and supplement the influence of papers. The USA, China, Japan, Italy, and the UK are the most productive countries, but China and Japan are significantly inferior to other countries in terms of research influence. Four of the top ten authors are at the center of the collaboration network. LUPUS is the most contributing journal. The theme of systemic lupus erythematosus research mainly focuses on the pathogenesis, treatment, and management of SLE, and the emerging trend is related research on machine learning and immune cells. CONCLUSION: This study shows the research status of SLE, clarifies the main contributors in this field, discusses and analyzes the research hotspots and trends in this field, and provides reference for further research in this field to promote the development of SLE research. Key Points • Through bibliometric analysis, Altmetric analysis, and visual analysis, we reveal the global productivity characteristics of SLE-related papers in the past 10 years. • The number of global SLE-related studies has shown a significant increase, indicating that SLE is still a hot topic and deserves further study. • Citation analysis and Altmetric analysis can mutually prove and supplement the influence of papers, and the attention of related literature among non-professional researchers is increasing. • The theme of SLE research mainly focuses on the pathogenesis, treatment, and management of SLE. The emerging trend is machine learning and immune cells, which may provide new strategies for the diagnosis and treatment of SLE in the future.

Analysis of TLR10 gene polymorphisms in patients with rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic systemic disease characterized by inflammatory synovitis, and genetic factors play the greatest role in RA. This study aimed to investigate the relationship between Toll-like receptor 10(TLR10) gene polymorphisms and susceptibility to RA. METHODS: A total of 271 patients with RA and an equal number of healthy controls were included, and the TLR10 rs2101521, rs10004195 and rs11725309 loci were genotyped by time-of-flight mass spectrometry. RESULTS: Compared with healthy controls, Individuals carrying the rs2101521 G allele had an increased risk of developing RA (P = 0.01; odds ratio (OR) = 1.367; 95 % confidence interval (CI): 1.076-1.736). Individuals with the rs2101521 GG genotype had a greater risk of RA (P = 0.01; OR = 1.816; 95 % CI: 1.161-2.984). Stratified analysis demonstrated a greater prevalence of positive anti-cyclic citrullinated peptide (CCP)antibody in patients carrying the rs2101521 G allele (P = 0.03). Additionally, patients with the rs11725309 CT genotype had elevated levels of C-reactive protein (CRP)(P = 0.007). CONCLUSION: In conclusion, TLR10 gene polymorphisms are associated with RA susceptibility.

PARP1 inhibition prevents oxidative stress in age-related hearing loss via PAR-Ca2+-AIF axis in cochlear strial marginal cells.

Studies have highlighted oxidative damage in the inner ear as a critical pathological basis for sensorineural hearing loss, especially the presbycusis. Poly(ADP-ribose) polymerase-1 (PARP1) activation responds to oxidative stress-induced DNA damage with pro-repair and pro-death effects resembling two sides of the same coin. PARP1-related cell death, known as parthanatos, whose underlying mechanisms are attractive research hotspots but remain to be clarified. In this study, we observed that aged rats showed stria vascularis degeneration and oxidative damage, and PARP1-dependent cell death was prominent in age-related cochlear disorganization and dysfunction. Based on oxidative stress model of primary cultured stria marginal cells (MCs), we revealed that upregulated PARP1 and PAR (Poly(ADP-ribose)) polymers are responsible for MCs oxidative death with high mitochondrial permeability transition pore (mPTP) opening and mitochondrial membrane potential (MMP) collapse, while inhibition of PARP1 ameliorated the adverse outcomes. Importantly, the PARylation of apoptosis-inducing factor (AIF) is essential for its conformational change and translocation, which subsequently causes DNA break and cell death. Concretely, the interaction of PAR and truncated AIF (tAIF) is the mainstream in the parthanatos pathway. We also found that the effects of AIF cleavage and release were achieved through calpain activity and mPTP opening, both of which could be regulated by PARP1 via mediation of mitochondria Ca2+ concentration. In conclusion, the PAR-Ca2+-tAIF signaling pathway in parthanatos contributes to the oxidative stress damage observed in MCs. Targeting PAR-Ca2+-tAIF might be a potential therapeutic strategy for the early intervention of presbycusis and other oxidative stress-associated sensorineural deafness.

Expanded Vermiculite/D-Mannitol as Shape-Stable Phase Change Material for Medium Temperature Heat Storage.

Aiming to promote the application of D-mannitol in the field of phase change thermal storage, obstacles, including low thermal storage efficiency and high supercooling, should be properly disposed of. The adoption of adaptable and low-cost supporting materials to make shape-stable phase change materials (ss-PCMs) affordable is a primary solution to solve the above shortcomings. In this study, high-performance ss-PCM for effective medium-temperature heat storage was prepared using expanded vermiculite as the support for D-mannitol preservation. Among the three candidates that treated the raw vermiculite by dilute acid, calcination, and microwave heating, the calcinated expanded vermiculite (CV) was characterized as the most suitable one. After impregnating D-mannitol into the CV carrier by vacuum, a melting enthalpy of 205.1 J/g and a crystallization enthalpy of 174.1 J/g were achieved by the as-received CV/D-mannitol ss-PCM. Additionally, the supercooling of the ss-PCM was reduced to 45.6 °C. The novel CV/D-mannitol ss-PCM also exhibited excellent reusability and stability. All the findings indicate that the abundant and inexpensive CV exhibited great potential as the supporting material for D-mannitol-based ss-PCMs, which allow effective waste heat recovery and temperature regulation.

Distinct niche structures and intrinsic programs of fallopian tube and ovarian surface epithelial cells.

Epithelial ovarian cancer (EOC) can originate from either fallopian tube epithelial (FTE) or ovarian surface epithelial (OSE) cells, but with different latencies and disease outcomes. To address the basis of these differences, we performed single cell RNA-sequencing of mouse cells isolated from the distal half of fallopian tube (FT) and surface layer of ovary. We find at the molecular level, FTE secretory stem/progenitor cells and OSE cells resemble mammary luminal progenitors and basal cells, respectively. An FT stromal subpopulation, enriched with Pdgfra + and Esr1 + cells, expresses multiple secreted factor (e.g., IGF1) and Hedgehog pathway genes and may serve as a niche for FTE cells. In contrast, Lgr5 + OSE cells express similar genes largely by themselves, raising a possibility that they serve as their own niche. The differences in intrinsic expression programs and niche organizations of FTE and OSE cells may contribute to their different courses toward the development of EOCs.

Bibliometric and altmetric analysis of research relating to antiphospholipid syndrome based on VOS viewer (2011-2021).

BACKGROUND: Antiphospholipid syndrome is an autoimmune disorder characterized by recurrent vascular thrombosis and pregnancy losses in the presence of persistently positive antiphospholipid antibodies. Bibliometric analysis and altmetric analysis are methods of analyzing academic productivity and influence. Currently, the assessment of antiphospholipid syndrome through the above analyses is lacking. This study investigated the quantity and quality of studies in the field of antiphospholipid syndrome and revealed the characteristics of worldwide productivity on this disease by the bibliometric analysis and altmetric analysis. METHODS: The terms "APS," "antiphospholipid syndrome," "antiphospholipid-antibody syndrome," and "Hughes syndrome" were searched on the Web of Science Core Collection from January 1, 2011, to December 31, 2021. Original articles and reviews were selected. We set the filters as "English." RESULTS AND CONCLUSION: A total of 1818 articles were retrieved from 68 countries, of which 20 met the criteria of major active countries. High-income countries contributed 1341 articles (73.48%). The number of articles annually increased significantly in the 10-year period (P < 0.001). The USA (253, 13.91%) was the most productive country. Adjusted by population, Serbia was top of the list. According to the gross domestic product analysis, Serbia ranked first. The most used keywords such as thrombosis and antiphospholipid antibodies were presented by keywords analyses. A content analysis found antithrombotic and anticoagulant therapy as research hotspots. A significant correlation was detected between average citations and altmetric attention scores (P = 0.002) and Mendeley readers count (P < 0.001). From 2011 to 2021, the number of global articles increased rapidly. Most papers came from high-income countries. The relationship between the bibliometric and altmetric analyses were basically consistent; therefore the two can prove/complement each other. Key points • We revealed the global productivity characteristics of the papers related to antiphospholipid syndrome by using the methods of bibliometric analysis and altmetric analysis. • We found the most selected articles that describe the treatment of antiphospholipid syndrome, especially antithrombotic and anticoagulant treatments, which may be the current research hotspot.

Cochlear metabolomics, highlighting novel insights of purine metabolic alterations in age-related hearing loss.

Aging is an inevitable phase in mammals that leads to health impairments, including hearing loss. Age-related hearing loss (AHL) leads to psychosocial problems and cognitive decline in the elderly. In this study, mean thresholds of auditory brainstem responses (ABR) and distortion-product otoacoustic emissions (DPOAE) increased at multiple frequencies in aged rats (14 months old) compared to young rats (2 months old). Using untargeted ultra-high performance liquid chromatography-mass spectroscopy (LC-MS), we quantified molecular metabolic markers in the cochlea of aged rats with hearing loss. A total of 137 different metabolites were identified in two groups, highlighting several prominent metabolic pathways related to purine metabolism; glycine, serine, and threonine metabolism; arginine and proline metabolism; and pyrimidine metabolism. In addition, the beneficial effects of purine supplementation were demonstrated in a mimetic model of senescent marginal cells (MCs). Overall, altered metabolic profiling is both the cause and manifestation of pathology, and our results suggest that cellular senescence and dysfunctional cochlear metabolism may contribute to the progression of AHL. These findings are seminal in elucidating the pathophysiological mechanisms underlying AHL and serve as a basis for future clinical predictions and interventions in AHL.

Selective inhibition of integrin αvß6 leads to rapid induction of urinary bladder tumors in cynomolgus macaques.

Administration of a novel and selective small molecule integrin αvß6 inhibitor, MORF-627, to young cynomolgus monkeys for 28 days resulted in the rapid induction of epithelial proliferative changes in the urinary bladder of 2 animals, in the absence of test agent genotoxicity. Microscopic findings included suburothelial infiltration by irregular nests and/or trabeculae of epithelial cells, variable cytologic atypia, and high mitotic rate, without invasion into the tunica muscularis. Morphologic features and patterns of tumor growth were consistent with a diagnosis of early-stage invasive urothelial carcinoma. Ki67 immunohistochemistry demonstrated diffusely increased epithelial proliferation in the urinary bladder of several monkeys, including those with tumors, and αvß6 was expressed in some epithelial tissues, including urinary bladder, in monkeys and humans. Spontaneous urothelial carcinomas are extremely unusual in young healthy monkeys, suggesting a direct link of the finding to the test agent. Inhibition of integrin αvß6 is intended to locally and selectively block transforming growth factor beta (TGF-ß) signaling, which is implicated in epithelial proliferative disorders. Subsequent in vitro studies using a panel of integrin αvß6 inhibitors in human bladder epithelial cells replicated the increased urothelial proliferation observed in monkeys and was reversed through exogenous application of TGF-ß. Moreover, analysis of in vivo models of liver and lung fibrosis revealed evidence of epithelial hyperplasia and cell cycle dysregulation in mice treated with integrin αvß6 or TGF-ß receptor I inhibitors. The cumulative evidence suggests a direct link between integrin αvß6 inhibition and decreased TGF-ß signaling in the local bladder environment, with implications for epithelial proliferation and carcinogenesis.

LINC00665 interacts with BACH1 to activate Wnt1 and mediates the M2 polarization of tumor-associated macrophages in GC.

Gastric cancer (GC) remains one of the prevalent causes of cancer-related deaths globally. Long non-coding RNAs (lncRNAs) have been associated with different cancers. The polarization of macrophages towards the M2 (alternatively activated) phenotype promotes immunologic tolerance and can induce gastric tumorigenesis. Thus far, lncRNAs have been shown to modulate the differentiation of immune cells. Here, we investigated the biological effects of LINC00665 on the progression of GC and explored the mechanisms underlying its ability to mediate the polarization of macrophages towards the M2 phenotype. We report that the levels of LINC00665 were increased in GC tissues. Furthermore, this increase in LINC00665 expression could be associated with decreased overall survival (OS), progression-free survival (PFS), and post-progression survival (PPS). Using cell-based macrophage polarization models, we demonstrated that LINC00665 upregulation in GC cells facilitated the polarization of macrophages towards the M2 but not M1 (classically activated) phenotype. Furthermore, the loss of LINC00665 prevented the M2 polarization of macrophages. Mechanically, we identified that Wnt1 was the downstream target of LINC00665. Additionally, LINC00665 could directly interact with the transcription factor BTB domain and CNC homology 1 (BACH1). The interaction between LINC00665 and BACH1 resulted in the activation and binding of BACH1 to the Wnt1 promoters. Furthermore, BACH1 silencing could inhibit GC progression, which highlighted a crucial role for BACH1 in LINC00665-mediated Wnt1 activation. In addition, genetic Wnt1 overexpression effectively abolished the repression of Wnt signaling after BACH1 depletion and mediated GC development by supporting M2 macrophage polarization. In conclusion, we report that LINC00665 modulates M2 macrophage polarization and suggest that it may facilitate macrophage-dependent GC progression.

Analysis of Community Composition of Bacterioplankton in Changle Seawater in China by Illumina Sequencing Combined with Bacteria Culture.

OBJECTIVES: To characterize the abundance and relative composition of seawater bacterioplankton communities in Changle city using Illumina MiSeq sequencing and bacterial culture techniques. METHODS: Seawater samples and physicochemical factors were collected from the coastal zone of Changle city on 8 September 2019. Nineteen filter membranes were obtained after using a suction filtration system. We randomly selected eight samples for total seawater bacteria (SWDNA group) sequencing and three samples for active seawater bacteria (SWRNA group) sequencing by Illumina MiSeq. The remaining eight samples were used for bacterial culture and identification. Alpha diversity including species coverage (Coverage), species diversity (Shannon-Wiener and Simpson index), richness estimators (Chao1), and abundance-based richness estimation (ACE) were calculated to assess biodiversity of seawater bacterioplankton. Beta diversity was used to evaluate the differences between samples. The species abundance differences were determined using the Wilcoxon rank-sum test. Statistical analyses were performed in R environment. RESULTS: The Alpha diversity in the SWDNA group in each index was ACE 3206.99, Chao1 2615.12, Shannon 4.64, Simpson 0.05, and coverage 0.97; the corresponding index was ACE 1199.55, Chao1 934.75, Shannon 3.49, Simpson 0.09, and coverage 0.99. The sequencing results of seawater bacterial genes in the coastal waters of Changle city showed that the phyla of high-abundance bacteria of both the SWDNA and SWRNA groups included Cyanobacteria, Proteobacteria, and Bacteroidetes. The main classes included Oxyphotobacteria, Alphaproteobacteria, and Gammaproteobacteria. The main genera included Synechococcus CC9902, Chloroplast, and Cyanobium_PCC-6307. Beta diversity analysis showed a significant difference between the SWDNA and SWRNA groups (P < 0.05). The species abundance differences between SWDNA and SWRNA groups after Wilcoxon rank-sum test showed that, at the phylum level, Actinomycetes was more abundant in SWDNA group (9.17 vs 1.02%, P < 0.05); at the class level, Actinomycetes (δ- Proteus) was more abundant in SWDNA group (9.47% vs 1.01%, P < 0.05); and at the genus level, Chloroplast was more abundant in SWRNA group (13.07% vs 44.57%, P < 0.05). Nine species and 53 colonies were found by bacterial culture: 20 strains of Vibrio (37.74%), 22 strains of Enterobacter (41.51%), and 11 strains of non-fermentative bacteria (20.75%). CONCLUSION: Illumi MiSeq sequencing of seawater bacteria revealed that the total bacterial community groups and the active bacterial community groups mainly comprised Cyanobacteria, Proteobacteria, and Bacteroides at the phylum level; Oxyphotobacteria, α-Proteobacteria, and γ-Proteobacteria at the class level; with Synechococcus_CC9902, Chloroplast, and Cyanobium_PCC-6307 comprising the predominant genera. Exploring the composition and differences of seawater bacteria assists understanding regarding the biodiversity and the infections related to seawater bacteria along the coast of the Changle, provides information that will aid in the diagnosis and treatment of such infections.

High-dose gatifloxacin-based shorter treatment regimens for MDR/RR-TB.

SETTING: The shorter treatment regimen (STR) for multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB) has achieved successful outcomes in many countries. However, there are few studies on high-dose gatifloxacin-based STR with adverse drug reactions (ADRs) and management. DESIGN: A prospective observational study was conducted with MDR/RR-TB patients who were treated with a standardized 9 or 12 - month regimen: including gatifloxacin (Gfx), clofazimine (Cfz), ethambutol (EMB), and pyrazinamide (PZA), and supplemented by amikacin (Am), isoniazid (INH), and prothionamide (Pto) during an intensive phase of 4 or 6 - month. Monitored ADRs monthly until treatment completion and then followed up every three months for one year. RESULTS: Among the 42 eligible patients, 35 (83.3%) completed treatment successfully, 1 (2.4%) lost to follow-up (LTFU), and 6 (14.3%) failed due to ADRs, with no death. The most important ADR was drug-induced liver damage, which occurred in 24 out of 42 (57.1%) patients and resulted in 4 (9.5%) failed treatments and 4 (9.5%) adjusted treatments. QT interval prolongation occurred in 17 out of 42 (40.5%) patients, 9 (21.4%) of them with the corrected QT interval according to Fridericia (QTcF) > 500 ms resulting in 7 (16.7%) adjusted treatments. CONCLUSIONS: This study confirmed the effectiveness of the high-dose gatifloxacin-based STR but severe ADRs, especially hepatotoxicity and QT interval prolongation should never be ignored.