Diversity and distribution of a prevalent Microviridae group across the global oceans.

Small single-stranded DNA phages of the Microviridae family are diverse and prevalent in oceans. Our understanding of Microviridae phages that infect the ecologically important marine Roseobacter is currently limited, comprising few isolates. Here, we report six roseophages that infect Roseobacter RCA strains. Genomic and phylogenetic analyses revealed that they were new members of the previously identified subfamily Occultatumvirinae. Additionally, 232 marine uncultivated virus genomes (UViGs) affiliated to Occultatumvirinae were obtained from environmental genome datasets. Phylogenomic analysis revealed that marine Occultatumvirinae phages could be further grouped into 11 subgroups. Moreover, meta-omics based read-mapping analysis showed that Occultatumvirinae phages were globally distributed, with two low G + C subgroups showing the most prevalent distribution. Furthermore, one phage in subgroup 2 was found to be extremely ubiquitous. Overall, this study expands our understanding of the diversity and ecology of the Occultatumvirinae microviruses in the ocean and highlights their ecological impacts.

Novel phage infecting the Roseobacter CHUG lineage reveals a diverse and globally distributed phage family.

Bacteriophages play an essential role in shaping the diversity and metabolism of bacterial communities. Marine Roseobacter group is an abundant heterotrophic bacterial group that is involved in many major element cycles, especially carbon and sulfur. Members of the Roseobacter CHUG (Clade Hidden and Underappreciated Globally) lineage are globally distributed and are activated in pelagic marine environments. In this study, we isolated and characterized a phage, CRP-810, that infects the CHUG strain FZCC0198. The genome of CRP-810 was dissimilar to those of other known phages. Additionally, 251 uncultured viral genomes (UViGs) closely related to CRP-810 were obtained from the uncultivated marine viral contig databases. Comparative genomic and phylogenetic analyses revealed that CRP-810 and these related UViGs exhibited conserved genome synteny, representing a new phage family with at least eight subgroups. Most of the CRP-810-type phages contain an integrase gene, and CRP-810 can be integrated into the host genome. Further analysis revealed that three CRP-810-type members were prophages found in the genomes of marine SAR11, Poseidonocella, and Sphingomonadaceae. Finally, viromic read-mapping analysis showed that CRP-810-type phages were globally distributed and displayed distinct biogeographic patterns related to temperature and latitude. Many members with a lower G + C content were mainly distributed in the trade station, whereas members with a higher G + C content were mainly distributed in polar and westerlies station, indicating that the niche differentiation of phages was subject to host adaptation. Collectively, these findings identify a novel phage family and expand our understanding of phylogenetic diversity, evolution, and biogeography of marine phages. IMPORTANCE: The Roseobacter CHUG lineage, affiliated with the Pelagic Roseobacter Cluster (PRC), is widely distributed in the global oceans and is active in oligotrophic seawater. However, knowledge of the bacteriophages that infect CHUG members is limited. In this study, a CHUG phage, CRP-810, that infects the CHUG strain FZCC0198, was isolated and shown to have a novel genomic architecture. In addition, 251 uncultured viral genomes closely related to CRP-810 were recovered and included in the analyses. Phylogenomic analyses revealed that the CRP-810-type phages represent a new phage family containing at least eight genus-level subgroups. Members of this family were predicted to infect various marine bacteria. We also demonstrated that the CRP-810-type phages are widely distributed in global oceans and display distinct biogeographic patterns related to latitude. Collectively, this study provides important insights into the genomic organization, diversity, and ecology of a novel phage family that infect ecologically important bacteria in the global ocean.

Genome sequences of the first Autographiviridae phages infecting marine Roseobacter.

The ubiquitous and abundant marine phages play critical roles in shaping the composition and function of bacterial communities, impacting biogeochemical cycling in marine ecosystems. Autographiviridae is among the most abundant and ubiquitous phage families in the ocean. However, studies on the diversity and ecology of Autographiviridae phages in marine environments are restricted to isolates that infect SAR11 bacteria and cyanobacteria. In this study, ten new roseophages that infect marine Roseobacter strains were isolated from coastal waters. These new roseophages have a genome size ranging from 38 917 to 42 634 bp and G+C content of 44.6-50 %. Comparative genomics showed that they are similar to known Autographiviridae phages regarding gene content and architecture, thus representing the first Autographiviridae roseophages. Phylogenomic analysis based on concatenated conserved genes showed that the ten roseophages form three distinct subgroups within the Autographiviridae, and sequence analysis revealed that they belong to eight new genera. Finally, viromic read-mapping showed that these new Autographiviridae phages are widely distributed in global oceans, mostly inhabiting polar and estuarine locations. This study has expanded the current understanding of the genomic diversity, evolution and ecology of Autographiviridae phages and roseophages. We suggest that Autographiviridae phages play important roles in the mortality and community structure of roseobacters, and have broad ecological applications.

Efficacy of acupotomy combined with sodium hyaluronate versus sodium hyaluronate alone in the treatment of knee osteoarthritis: A meta-analysis.

BACKGROUND: The efficacy of acupotomy combined with hyaluronic sodium acid in the treatment of knee osteoarthritis (KOA) is unclear. Therefore, this meta-analysis aims to evaluate the efficacy of acupotomy combined with hyaluronic sodium acid compared with hyaluronic sodium acid alone in the treatment of KOA. METHODS: Studies from 8 Online databases were searched on KOA treatment using acupotomy combined with sodium hyaluronate until May 2022. The primary outcome indicator was clinical effectiveness, and the secondary outcome indicators included the visual analogue scale scores and Lysholm scores. We calculated the weighted mean difference (WMD) or relative risk for all relevant outcomes. RESULTS: Nine studies were identified, involving 644 cases. The results showed that acupotomy combined with intra-articular sodium hyaluronate injection for KOA was superior to sodium hyaluronate injection alone in terms of clinical effectiveness (relative risk = 1.17, 95% confidence interval [CI]: 1.09-1.25, P < .001) and visual analogue scale (WMD = -2.1, 95% CI: -2.25 to 1.95, P < .001), Lysholm score (WMD = 13.83, 95% CI: 3.47-24.19, P = .009). CONCLUSION: Acupotomy combined with intra-articular sodium hyaluronate injection for KOA is superior to sodium hyaluronate injection alone. Limited by the number and quality of included studies, this conclusion still needs to be verified by more high-quality Research. INPLASY REGISTRATION NUMBER: INPLASY202350029.

The Association Between Socioeconomic Factors at Diagnosis and Survival in Medulloblastoma: A Propensity Score-Matched Analysis and Population-Based Study.

BACKGROUND: Medulloblastoma (MB) is the most common malignant brain tumor of childhood. The associations between socioeconomic statuses (SES) and survival outcomes of medulloblastoma remain unclear. The aim of this study was to develop a nomogram to predict medulloblastoma specific death (MBSD) and overall survival (OS) in patients with medulloblastoma, taking into account socioeconomic factors in patients with medulloblastoma. METHODS: We included patients diagnosed with MB between 1975 and 2016 from the Surveillance, Epidemiology, and End Results database. Propensity Score Matching (PSM) was performed to reduce selection bias. Multivariate cox proportional hazards model was used to assess SES impact and clinically relevant variables of medulloblastoma specific death and overall survival. Independent prognostic factors determined by multivariate analysis were used to construct nomograms. RESULTS: A total of 2660 patients were enrolled after matching. Study showed unemployed rate (MBSD, high level vs. low level, P = 0.020) (OS, high level vs. low level, P = 0.017), and marital status (OS, married vs unmarried/unknown, P = 0.029) were important factors affecting prognosis of medulloblastoma in male. Meanwhile, median household income (MBSD, quartile 1 vs. quartile 3, P = 0.047) (OS, quartile 1 vs. quartile 2, P = 0.017) (OS, quartile 1 vs. quartile 3, P = 0.014), residence (MBSD, urban vs. rural, P = 0.041), and insurance status (MBSD, insured vs. uninsured/unknown, P = 0.002)(OS, insured vs. uninsured/unknown, P = 0.001) were significant factors affecting prognosis of medulloblastoma in female. Through the calibration plot and C-index test, our nomogram was also of predictive significance. CONCLUSIONS: The unique features of MB have provided a scenario for analysis of the impact of racial, ethnic, gender, and socioeconomic factors. The current findings have important public health implications for achieving the goal of a healthy population. Given the known morbidity rates, long-term psychological, financial and medical burdens that these children and their families must bear, it is critical to identify and address these gaps.

Genomic diversity and biogeographic distributions of a novel lineage of bacteriophages that infect marine OM43 bacteria.

The marine methylotrophic OM43 clade is considered an important bacterial group in coastal microbial communities. OM43 bacteria, which are closely related to phytoplankton blooms, have small cell sizes and streamlined genomes. Bacteriophages profoundly shape the evolutionary trajectories, population dynamics, and physiology of microbes. The prevalence and diversity of several phages that infect OM43 bacteria have been reported. In this study, we isolated and sequenced two novel OM43 phages, MEP401 and MEP402. These phages share 90% of their open reading frames (ORFs) and are distinct from other known phage isolates. Furthermore, a total of 99 metagenomic viral genomes (MVGs) closely related to MEP401 and MEP402 were identified. Phylogenomic analyses suggest that MEP401, MEP402, and these identified MVGs belong to a novel subfamily in the family Zobellviridae and that they can be separated into two groups. Group I MVGs show conserved whole-genome synteny with MEP401, while group II MVGs possess the MEP401-type DNA replication module and a distinct type of morphogenesis and packaging module, suggesting that genomic recombination occurred between phages. Most members in these two groups were predicted to infect OM43 bacteria. Metagenomic read-mapping analysis revealed that the phages in these two groups are globally ubiquitous and display distinct biogeographic distributions, with some phages being predominant in cold regions, some exclusively detected in estuarine stations, and others displaying wider distributions. This study expands our knowledge of the diversity and ecology of a novel phage lineage that infects OM43 bacteria by describing their genomic diversity and global distribution patterns. IMPORTANCE OM43 phages that infect marine OM43 bacteria are important for host mortality, community structure, and physiological functions. In this study, two OM43 phages were isolated and characterized. Metagenomic viral genome (MVG) retrieval using these two OM43 phages as baits led to the identification of two phage groups of a new subfamily in the family Zobellviridae. We found that group I MVGs share similar genomic content and arrangement with MEP401 and MEP402, whereas group II MVGs only possess the MEP401-type DNA replication module. Metagenomic mapping analysis suggests that members in these two groups are globally ubiquitous with distinct distribution patterns. This study provides important insights into the genomic diversity and biogeography of the OM43 phages in the global ocean.

Genomic analysis and characterization of phages infecting the marine Roseobacter CHAB-I-5 lineage reveal a globally distributed and abundant phage genus.

Marine phages play an important role in marine biogeochemical cycles by regulating the death, physiological metabolism, and evolutionary trajectory of bacteria. The Roseobacter group is an abundant and important heterotrophic bacterial group in the ocean, and plays an important role in carbon, nitrogen, sulfur and phosphorus cycling. The CHAB-I-5 lineage is one of the most dominant Roseobacter lineages, but remains largely uncultured. Phages infecting CHAB-I-5 bacteria have not yet been investigated due to the lack of culturable CHAB-I-5 strains. In this study, we isolated and sequenced two new phages (CRP-901 and CRP-902) infecting the CHAB-I-5 strain FZCC0083. We applied metagenomic data mining, comparative genomics, phylogenetic analysis, and metagenomic read-mapping to investigate the diversity, evolution, taxonomy, and biogeography of the phage group represented by the two phages. The two phages are highly similar, with an average nucleotide identity of 89.17%, and sharing 77% of their open reading frames. We identified several genes involved in DNA replication and metabolism, virion structure, DNA packing, and host lysis from their genomes. Metagenomic mining identified 24 metagenomic viral genomes closely related to CRP-901 and CRP-902. Genomic comparison and phylogenetic analysis demonstrated that these phages are distinct from other known viruses, representing a novel genus-level phage group (CRP-901-type). The CRP-901-type phages do not contain DNA primase and DNA polymerase genes, but possess a novel bifunctional DNA primase-polymerase gene with both primase and polymerase activities. Read-mapping analysis showed that the CRP-901-type phages are widespread across the world's oceans and are most abundant in estuarine and polar waters. Their abundance is generally higher than other known roseophages and even higher than most pelagiphages in the polar region. In summary, this study has greatly expanded our understanding of the genetic diversity, evolution, and distribution of roseophages. Our analysis suggests that the CRP-901-type phage is an important and novel marine phage group that plays important roles in the physiology and ecology of roseobacters.

Clinical efficacy and safety of the combination of mesenchymal stem cells and scaffolds in the treatment of knee osteoarthritis: Protocol for systematic review and meta-analysis.

BACKGROUND: Mesenchymal stem cells (MSCs) injection combined scaffolds for knee osteoarthritis (OA) is a relatively new treatment for knee OA and has not yet gained popularity. So, the effectiveness, safety is worthy to be explored. We performed a protocol for systematic review and meta-analysis to evaluate the efficacy and safety of the combination of MSCs and scaffolds in the treatment of knee OA. METHODS: A literature search was performed in October 2022 without restriction to regions, publication types or languages. The primary sources were the electronic databases of PubMed, EMBASE, Cochrane Library, Web of Science and the ClinicalTrials.gov. Risk of bias was assessed using the Cochrane Collaboration's risk of bias tool for randomized controlled trials. Statistical analyses were performed utilizing Review Manager 5 (The Nordic Cochrane Center, Copenhagen, Denmark). RESULTS: Visual analog scale score, Western Ontario and McMaster Universities Osteoarthritis Index, Lysholm knee scale and adverse events will be assessed. CONCLUSION: The systematic review will provide evidence to assess the effectiveness and safety of MSCs combined scaffolds for the treatment of knee OA.