Agomir-122-loaded nanoparticles coated with cell membrane of activated fibroblasts to treat frozen shoulder based on homologous targeting.

As a common musculoskeletal disorder, frozen shoulder is characterized by thickened joint capsule and limited range of motion, affecting 2-5% of the general population and more than 20% of patients with diabetes mellitus. Pathologically, joint capsule fibrosis resulting from fibroblast activation is the key event. The activated fibroblasts are proliferative and contractive, producing excessive collagen. Albeit high prevalence, effective anti-fibrosis modalities, especially fibroblast-targeting therapies, are still lacking. In this study, microRNA-122 was first identified from sequencing data as a potential therapeutic agent to antagonize fibroblast activation. Then, Agomir-122, an analog of microRNA-122, was loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Agomir-122@NP), a carrier with excellent biocompatibility for the agent delivery. Moreover, relying on the homologous targeting effect, we coated Agomir-122@NP with the cell membrane derived from activated fibroblasts (Agomir-122@MNP), with an attempt to inhibit the proliferation, contraction, and collagen production of abnormally activated fibroblasts. After confirming the targeting effect of Agomir-122@MNP on activated fibroblasts in vitro, we proved that Agomir-122@MNP effectively curtailed fibroblasts activation, ameliorated joint capsule fibrosis, and restored range of motion in mouse models both prophylactically and therapeutically. Overall, an effective targeted delivery method was developed with promising translational value against frozen shoulder.

The dsRNA isolated from Escherichia coli infected with the MS2 bacteriophage induces the production of interferons.

Viral infections pose a significant threat to public health, and the production of interferons represents one of the most critical antiviral innate immune responses of the host. Consequently, the screening and identification of compounds or reagents that induce interferon production are of paramount importance. This study commenced with the cultivation of host bacterium 15,597, followed by the infection of Escherichia coli with the MS2 bacteriophage. Utilizing the J2 capture technique, a class of dsRNA mixtures (MS2+15,597) was isolated from the E. coli infected with the MS2 bacteriophage. Subsequent investigations were conducted on the immunostimulatory activity of the MS2+15,597 mixture. The results indicated that the dsRNA mixtures (MS2+15,597) extracted from E. coli infected with the MS2 bacteriophage possess the capability to activate innate immunity, thereby inducing the production of interferon-ß. These dsRNA mixtures can activate the RIG-I and TLR3 pattern recognition receptors, stimulating the expression of interferon stimulatory factors 3/7, which in turn triggers the NF-κB signaling pathway, culminating in the cellular production of interferon-ß to achieve antiviral effects. This study offers novel insights and strategies for the development of broad-spectrum antiviral drugs, potentially providing new modalities for future antiviral therapies.

Role of PDLIM1 in hepatic stellate cell activation and liver fibrosis progression.

Liver fibrosis is caused by chronic hepatic injury and may lead to cirrhosis, and even hepatocellular carcinoma. When hepatic stellate cells (HSCs) are activated by liver injury, they transdifferentiate into myofibroblasts, which secrete extracellular matrix proteins that generate the fibrous scar. Therefore, it is extremely urgent to find safe and effective drugs for HSCs activation treatment to prevent liver against fibrosis. Here, we reported that PDZ and LIM domain protein 1 (PDLIM1), a highly conserved cytoskeleton organization regulator, was significantly up-regulated in fibrotic liver tissues and TGF-ß-treated HSC-T6 cells. Through transcriptome analysis, we found that knockdown of PDLIM1 resulted in a significant downregulation of genes related to inflammation and immune-related pathways in HSC-T6 cells. Moreover, PDLIM1 knockdown significantly inhibited the activation of HSC-T6 cells and the trans-differentiation of HSC-T6 cells into myofibroblasts. Mechanistically, PDLIM1 is involved in the regulation of TGF-ß-mediated signaling pathways in HSCs activation. Thus, targeting PDLIM1 may provide an alternative method to suppress HSCs activation during liver injury. CCCTC-binding factor (CTCF), a master regulator of genome architecture, is upregulated during HSCs activation. PDLIM1 knockdown also indirectly reduced CTCF protein expression, however, CTCF binding to chromatin was not significantly altered by CUT&Tag analysis. We speculate that CTCF may cooperate with PDLIM1 to activate HSCs in other ways. Our results suggest that PDLIM1 can accelerate the activation of HSCs and liver fibrosis progression and could be a potential biomarker for monitoring response to anti-fibrotic therapy.

Dissection of 3D chromosome organization in Streptomyces coelicolor A3(2) leads to biosynthetic gene cluster overexpression.

The soil-dwelling filamentous bacteria, Streptomyces, is widely known for its ability to produce numerous bioactive natural products. Despite many efforts toward their overproduction and reconstitution, our limited understanding of the relationship between the host's chromosome three dimension (3D) structure and the yield of the natural products escaped notice. Here, we report the 3D chromosome organization and its dynamics of the model strain, Streptomyces coelicolor, during the different growth phases. The chromosome undergoes a dramatic global structural change from primary to secondary metabolism, while some biosynthetic gene clusters (BGCs) form special local structures when highly expressed. Strikingly, transcription levels of endogenous genes are found to be highly correlated to the local chromosomal interaction frequency as defined by the value of the frequently interacting regions (FIREs). Following the criterion, an exogenous single reporter gene and even complex BGC can achieve a higher expression after being integrated into the chosen loci, which may represent a unique strategy to activate or enhance the production of natural products based on the local chromosomal 3D organization.

FAIRE-MS reveals mitotic retention of transcriptional regulators on a proteome-wide scale.

Mitosis entails global and dramatic alterations, such as higher-order chromatin organization disruption, concomitant with global transcription downregulation. Cells reliably re-establishing gene expression patterns upon mitotic exit and maintaining cellular identities remain poorly understood. Previous studies indicated that certain transcription factors (TFs) remain associated with individual loci during mitosis and serve as mitotic bookmarkers. However, it is unclear which regulatory factors remain bound to the compacted mitotic chromosomes. We developed formaldehyde-assisted isolation of regulatory elements-coupled mass spectrometry (FAIRE-MS) that combines FAIRE-based open chromatin-associated protein pull-down and mass spectrometry (MS) to quantify the open chromatin-associated proteome during the interphase and mitosis. We identified 189 interphase and mitosis maintained (IM) regulatory factors using FAIRE-MS and found intrinsically disordered proteins and regions (IDP(R)s) are highly enriched, which plays a crucial role in liquid-liquid phase separation (LLPS) and chromatin organization during the cell cycle. Notably, in these IDP(R)s, we identified mitotic bookmarkers, such as CEBPB, HMGB1, and TFAP2A, and several factors, including MAX, HMGB3, hnRNP A2/B1, FUS, hnRNP D, and TIAL1, which are at least partially bound to the mitotic chromosome. Furthermore, it will be essential to study whether these IDP(R)s through LLPS helps cells transit from mitosis to the G1 phase during the cell cycle.

Targeted screening of genetic associations with COVID-19 susceptibility and severity.

The COVID-19 pandemic has resulted in great morbidity and mortality worldwide and human genetic factors have been implicated in the susceptibility and severity of COVID-19. However, few replicate researches have been performed, and studies on associated genes mainly focused on genic regions while regulatory regions were a lack of in-depth dissection. Here, based on previously reported associated variants and genes, we designed a capture panel covering 1,238 candidate variants and 25 regulatory regions of 19 candidate genes and targeted-sequenced 96 mild and 145 severe COVID-19 patients. Genetic association analysis was conducted between mild and severe COVID-19 patients, between all COVID-19 patients and general population, or between severe COVID-19 patients and general population. A total of 49 variants were confirmed to be associated with susceptibility or severity of COVID-19 (p < 0.05), corresponding to 18 independent loci. Specifically, rs1799964 in the promoter of inflammation-related gene TNF, rs9975538 in the intron of interferon receptor gene IFNAR2, rs429358 in the exon of APOE, rs1886814 in the intron of FOXP4-AS1 and a list of variants in the widely reported 3p21.31 and ABO gene were confirmed. It is worth noting that, for the confirmed variants, the phenotypes of the cases and controls were highly consistent between our study and previous reports, and the confirmed variants identified between mild and severe patients were quite different from those identified between patients and general population, suggesting the genetic basis of susceptibility and severity of SARS-CoV-2 infection might be quite different. Moreover, we newly identified 67 significant associated variants in the 12 regulatory regions of 11 candidate genes (p < 0.05). Further annotation by RegulomeDB database and GTEx eQTL data filtered out two variants (rs11246060 and rs28655829) in the enhancer of broad-spectrum antiviral gene IFITM3 that might affect disease severity by regulating the gene expression. Collectively, we confirmed a list of previously reported variants and identified novel regulatory variants associated with susceptibility and severity of COVID-19, which might provide biological and clinical insights into COVID-19 pathogenesis and treatment.

Pilot genome-wide association study of antibody response to inactivated SARS-CoV-2 vaccines.

Vaccines are a key weapon against the COVID-19 pandemic caused by SARS-CoV-2. However, there are inter-individual differences in immune response to SARS-CoV-2 vaccines and genetic contributions to these differences have barely been investigated. Here, we performed genome-wide association study (GWAS) of antibody levels in 168 inactivated SARS-CoV-2 vaccine recipients. A total of 177 SNPs, corresponding to 41 independent loci, were identified to be associated with IgG, total antibodies or neutral antibodies. Specifically, the rs4543780, the intronic variant of FAM89A gene, was associated with total antibodies level and was annotated as a potential regulatory variant affecting gene expression of FAM89A, a biomarker differentiating bacterial from viral infections in febrile children. These findings might advance our knowledge of the molecular mechanisms driving immunity to SARS-CoV-2 vaccine.

Profiling and characterization of constitutive chromatin-enriched RNAs.

RNA species act as architectural scaffolds for nuclear structures including chromatin in eukaryotic cells. However, the composition and dynamics of tightly bound chromatin-associated RNAs during mitosis remains elusive. Here we report the identification of chromatin-enriched RNA (cheRNAs) by biochemical nuclear fractionation coupled with RNA sequencing in both interphase and mitotic phase of A549 and HeLa-S3 cell lines. We show that highly abundant cheRNAs, mostly small noncoding RNAs, are largely maintained in mitotic chromatin, and constitute a substantial part of chromatin RNA throughout cell cycle. We also show that the mitotic retained cheRNAs tend to be cell type nonspecific and might be involved in chromatin accessibility and epigenetic memory of gene expression control. Therefore, we reveal an unexpected set of cell type-nonspecific mitotic retained chromatin-enriched RNAs. We anticipate that the landscape of RNA composition of chromatin both in interphase and mitotic phase would help understanding structure and function of chromatin.

The role of ZNF143 overexpression in rat liver cell proliferation.

BACKGROUND: Zinc finger protein 143(ZNF143), a member of the Krüppel C2H2-type zinc finger protein family, is strongly associated with cell cycle regulation and cancer development. A recent study suggested that ZNF143 plays as a transcriptional activator that promotes hepatocellular cancer (HCC) cell proliferation and cell cycle transition. However, the exact biological role of ZNF143 in liver regeneration and normal liver cell proliferation has not yet been investigated. METHODS: In our study, we constructed a stable rat liver cell line (BRL-3A) overexpressing ZNF143 and then integrated RNA-seq and Cleavage Under Targets and Tagmentation (CUT&Tag) data to identify the mechanism underlying differential gene expression. RESULTS: Our results show that ZNF143 expression is upregulated during the proliferation phase of liver regeneration after 2/3 partial hepatectomy (PH). The cell counting kit-8 (CCK-8) assay, EdU staining and RNA-seq data analyses revealed that ZNF143 overexpression (OE) significantly inhibited BRL-3A cell proliferation and cell cycle progression. We then performed CUT&Tag assays and found that approximately 10% of ZNF143-binding sites (BSs) were significantly changed genome-wide by ZNF143 OE. However, CCCTC-binding factor (CTCF) binding to chromatin was not affected. Interestingly, the integration analysis of RNA-seq and CUT&Tag data showed that some of genes affected by ZNF143 differential BSs are in the center of each gene regulation module. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that these genes are critical in the maintenance of cell identity. CONCLUSION: These results indicated that the expression level of ZNF143 in the liver is important for the maintenance of cell identity. ZNF143 plays different roles in HCC and normal liver cells and may be considered as a potential therapeutic target in liver disease.

Changes in Higher-Order Chromosomal Structure of Klebsiella pneumoniae Under Simulated Microgravity.

Our previous work have shown that certain subpopulations of Klebsiella pneumoniae exhibit significant phenotypic changes under simulated microgravity (SMG), including enhanced biofilm formation and cellulose synthesis, which may be evoked by changes in gene expression patterns. It is well known that prokaryotic cells genomic DNA can be hierarchically organized into different higher-order three-dimensional structures, which can highly influence gene expression. It is remain elusive whether phenotypic changes induced by SMG in the subpopulations of K. pneumoniae are driven by genome higher-order structural changes. Here, we investigated the above-mentioned issue using the wild-type (WT) K. pneumoniae (WT was used as a control strain and continuously cultivated for 2 weeks under standard culture conditions of normal gravity) and two previous identified subpopulations (M1 and M2) obtained after 2 weeks of continuous incubation in a SMG device. By the combination of genome-wide chromosome conformation capture (Hi-C), RNA-seq and whole-genome methylation (WGS) analyses, we found that the along with the global chromosome interactions change, the compacting extent of M1, M2 subpopulations were much looser under SMG and even with an increase in active, open chromosome regions. In addition, transcriptome data showed that most differentially expressed genes (DEGs) were upregulated, whereas a few DEGs were downregulated in M1 and M2. The functions of both types DEGs were mainly associated with membrane fractions. Additionally, WGS analysis revealed that methylation levels were lower in M1 and M2. Using combined analysis of multi-omics data, we discovered that most upregulated DEGs were significantly enriched in the boundary regions of the variable chromosomal interaction domains (CIDs), in which genes regulating biofilm formation were mainly located. These results suggest that K. pneumoniae may regulate gene expression patterns through DNA methylation and changes in genome structure, thus resulting in new phenotypes in response to altered gravity.

dbGSRV: A manually curated database of genetic susceptibility to respiratory virus.

Human genetics has been proposed to play an essential role in inter-individual differences in respiratory virus infection occurrence and outcomes. To systematically understand human genetic contributions to respiratory virus infection, we developed the database dbGSRV, a manually curated database that integrated the host genetic susceptibility and severity studies of respiratory viruses scattered over literatures in PubMed. At present, dbGSRV contains 1932 records of genetic association studies relating 1010 unique variants and seven respiratory viruses, manually curated from 168 published articles. Users can access the records by quick searching, batch searching, advanced searching and browsing. Reference information, infection status, population information, mutation information and disease relationship are provided for each record, as well as hyperlinks to public databases in convenient of users accessing more information. In addition, a visual overview of the topological network relationship between respiratory viruses and associated genes is provided. Therefore, dbGSRV offers a convenient resource for researchers to browse and retrieve genetic associations with respiratory viruses, which may inspire future studies and provide new insights in our understanding and treatment of respiratory virus infection. Database URL: http://www.ehbio.com/dbGSRV/front/.

Sustained release of naringin from silk-fibroin-nanohydroxyapatite scaffold for the enhancement of bone regeneration.

Bone defects are a common challenge in the clinical setting. Bone tissue engineering (BTE) is an effective treatment for the clinical problem of large bone defects. In this study, we fabricated silk fibroin (SF)/hydroxyapatite (HAp) scaffolds inlaid with naringin poly lactic-co-glycolic acid (PLGA) microspheres, investigating the feasibility of their application in BTE. Naringin PLGA microspheres were manufactured and adhered to the SF/HAp scaffold. Bone mesenchymal stem cells (BMSCs) were inoculated onto the SF/HAp scaffold containing naringin PLGA microsphere to examine the biocompatibility of the SF/HAp scaffolds. A rabbit femoral distal bone defect model was used to evaluate the in vivo function of the SF/HAp scaffolds containing naringin-loaded PLGA microspheres. The current study demonstrated that SF/HAp scaffolds containing naringin-loaded PLGA microspheres show promise as osteo-modulatory biomaterials for bone regeneration.

Target-enriched sequencing enables accurate identification of bloodstream infections in whole blood.

Bloodstream infections are within the top ten causes of death globally, with a mortality rate of up to 70%. Gold standard blood culture testing is time-consuming, resulting in delayed, but accurate, treatment. Molecular methods, such as RT-qPCR, have limited targets in one run. We present a new Ampliseq detection system (ADS) combining target amplification and next-generation sequencing for accurate identification of bacteria, fungi, and antimicrobial resistance determinants directly from blood samples. In this study, we included removal of human genomic DNA during nucleic acid extraction, optimized the target sequence set and drug resistance genes, performed antimicrobial resistance profiling of clinical isolates, and evaluated mock specimens and clinical samples by ADS. ADS successfully identified pathogens at the species-level in 36 h, from nucleic acid extraction to results. Besides pathogen identification, ADS can also present drug resistance profiles. ADS enabled detection of all bacteria and accurate identification of 47 pathogens. In 20 spiked samples and 8 clinical specimens, ADS detected at least 92.81% of reads mapped to pathogens. ADS also showed consistency with the three culture-negative samples, and correctly identified pathogens in four of five culture-positive clinical blood specimens. This Ampliseq-based technology promises broad coverage and accurate pathogen identification, helping clinicians to accurately diagnose and treat bloodstream infections.

In vivo structure and dynamics of the SARS-CoV-2 RNA genome.

The dynamics of SARS-CoV-2 RNA structure and their functional relevance are largely unknown. Here we develop a simplified SPLASH assay and comprehensively map the in vivo RNA-RNA interactome of SARS-CoV-2 genome across viral life cycle. We report canonical and alternative structures including 5'-UTR and 3'-UTR, frameshifting element (FSE) pseudoknot and genome cyclization in both cells and virions. We provide direct evidence of interactions between Transcription Regulating Sequences, which facilitate discontinuous transcription. In addition, we reveal alternative short and long distance arches around FSE. More importantly, we find that within virions, while SARS-CoV-2 genome RNA undergoes intensive compaction, genome domains remain stable but with strengthened demarcation of local domains and weakened global cyclization. Taken together, our analysis reveals the structural basis for the regulation of replication, discontinuous transcription and translational frameshifting, the alternative conformations and the maintenance of global genome organization during the whole life cycle of SARS-CoV-2, which we anticipate will help develop better antiviral strategies.

Effects of Tranexamic Acid on Hemorrhage Control and Deep Venous Thrombosis Rate After Total Knee Arthroplasty: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Background: Total knee arthroplasty (TKA) surgery has a lot of complications, especially hemorrhage, which can be controlled via tranexamic acid (TXA). The guidelines endorse the integration of TXA interventions in the management of TKA-induced complications. However, uncertainty surrounds the effects of different TXA therapies. This frequentist model network meta-analysis (NMA) aims to compare hemorrhage control and deep venous thrombosis (DVT) rate of different TXA therapies in TKA. Methods: Articles were searched with the PubMed, Embase, Cochrane Library, and Web of Science from 1966 to October 2020. Randomized controlled trials (RCTs) comparing different TXA therapies, or with placebo in patients with TKA were included. Two investigators independently conducted article retrievals and data collection. The outcome was total blood loss and DVT rate. Effect size measures were mean differences (MDs), or odds ratios (ORs) with 95% confidence intervals (CIs). We conducted a random-effects NMA using a frequentist approach to estimate relative effects for all comparisons and rank treatments according to the mean rank and surface under the cumulative ranking curve values. All analyses were performed in Stata software or R software. The study protocol was registered with PROSPERO, number CRD42020202404. Results: We identified 1 754 citations and included 81 studies with data for 9 987 patients with TKA. Overall, all TXA therapies were superior to placebo for total blood loss in TKA. Of all TXA therapies, M therapy (IV/IV infusion + oral TXA > 3g) was most effective for total blood loss (MD=-688.48, -1084.04--328.93), followed by F therapy (IV TXA ≥ 15 mg/kg or 1 g three times). TXA therapies in this study are not associated with the increase of DVT risk. Conclusions: TXA therapies in this study are effective and safe for the treatment of TKA-induced complications. M therapy (IV/IV infusion + oral TXA > 3 g) may be the most effective TXA therapy for hemorrhage control. TXA therapies in this study do not increase DVT risk. Considering hemorrhage control and DVT rate simultaneously, F therapy (IV TXA ≥ 15 mg/kg or 1 g three times) may be suggested to apply for TKA, and this study may provide a crucial clue to future TXA use.

Naringin-inlaid silk fibroin/hydroxyapatite scaffold enhances human umbilical cord-derived mesenchymal stem cell-based bone regeneration.

OBJECTIVES: Large bone defects are a common, debilitating clinical condition that have substantial global health and economic burden. Bone tissue engineering technology has become one of the most promising approaches for regenerating defective bones. In this study, we fabricated a naringin-inlaid composite silk fibroin/hydroxyapatite (NG/SF/HAp) scaffold to repair bone defects. MATERIALS AND METHODS: The salt-leaching technology was used to fabricate the NG/SF/HAp scaffold. The cytocompatibility of the NG/SF/HAp scaffold was assessed using scanning electron microscopy, live/dead cell staining and phalloidin staining. The osteogenic and angiogenic properties were assessed in vitro and in vivo. RESULTS: The porous NG/SF/HAp scaffold had a well-designed biomimetic porous structure with osteoinductive and angiogenic activities. A gene microarray identified 854 differentially expressed genes between human umbilical cord-derived mesenchymal stem cells (hUCMSCs) cultured on SF-nHAp scaffolds and cells cultured on NG/SF/HAp scaffolds. The underlying osteoblastic mechanism was investigated using hUCMSCs in vitro. Naringin facilitated hUCMSC ingrowth into the SF/HAp scaffold and promoted osteogenic differentiation. The osteogenic and angiogenic capabilities of cells cultured in the NG/SF/HAp scaffold were superior to those of cells cultured in the SF/HAp scaffold. CONCLUSIONS: The data indicate the potential of the SF/HAp composite scaffold incorporating naringin for bone regeneration.

A systematic review and meta-analysis of children with coronavirus disease 2019 (COVID-19).

To provide a comprehensive and systematic analysis of demographic characteristics, clinical symptoms, laboratory findings, and imaging features of coronavirus disease 2019 (COVID-19) in pediatric patients. A meta-analysis was carried out to identify studies on COVID-19 from 25 December 2019 to 30 April 2020. A total of 48 studies with 5829 pediatric patients were included. Children of all ages were at risk for COVID-19. The main illness classification ranged as: 20% (95% confidence interval [CI]: 14%-26%; I2 = 91.4%) asymptomatic, 33% (95% CI: 23%-43%; I2 = 95.6%) mild and 51% (95% CI: 42%-61%; I2 = 93.4%) moderate. The typical clinical manifestations were fever 51% (95% CI: 45%-57%; I2 = 78.9%) and cough 41% (95% CI: 35%-47%, I2 = 81.0%). The common laboratory findings were normal white blood cell 69% (95% CI: 64%-75%; I2 = 58.5%), lymphopenia 16% (95% CI: 11%-21%; I2 = 76.9%) and elevated creatine-kinase MB 37% (95% CI: 25%-48%; I2 = 59.0%). The frequent imaging features were normal images 41% (95% CI: 30%-52%; I2 = 93.4%) and ground-glass opacity 36% (95% CI: 25%-47%; I2 = 92.9%). Among children under 1 year old, critical cases account for 14% (95% CI: 13%-34%; I2 = 37.3%) that should be of concern. In addition, vomiting occurred in 33% (95% CI: 18%-67%; I2 = 0.0%) cases that may also need attention. Pediatric patients with COVID-19 may experience milder illness with atypical clinical manifestations and rare lymphopenia. High incidence of critical illness and vomiting symptoms reward attention in children under 1 year old.

Changes in Vibrio natriegens Growth Under Simulated Microgravity.

The growth rate of bacteria increases under simulated microgravity (SMG) with low-shear force. The next-generation microbial chassis Vibrio natriegens (V. natriegens) is a fast-growing Gram-negative, non-pathogenic bacterium with a generation time of less than 10 min. Screening of a V. natriegens strain with faster growth rate was attempted by 2-week continuous long-term culturing under SMG. However, the rapid growth rate of this strain made it difficult to obtain the desired mutant strain with even more rapid growth. Thus, a mutant with slower growth rate emerged. Multi-omics integration analysis was conducted to explore why this mutant grew more slowly, which might inform us about the molecular mechanisms of rapid growth of V. natriegens instead. The transcriptome data revealed that whereas genes related to mechanical signal transduction and flagellin biogenesis were up-regulated, those involved in adaptive responses, anaerobic and nitrogen metabolism, chromosome segregation and cell vitality were down-regulated. Moreover, genome-wide chromosome conformation capture (Hi-C) results of the slower growth mutant and wide type indicated that SMG-induced great changes of genome 3D organization were highly correlated with differentially expressed genes (DEGs). Meanwhile, whole genome re-sequencing found a significant number of structure variations (SVs) were enriched in regions with lower interaction frequency and down-regulated genes in the slower growth mutant compared with wild type (WT), which might represent a prophage region. Additionally, there was also a decreased interaction frequency in regions associated with well-orchestrated chromosomes replication. These results suggested that SMG might regulate local gene expression by sensing stress changes through conformation changes in the genome region of genes involved in flagellin, adaptability and chromosome segregation, thus followed by alteration of some physiological characteristics and affecting the growth rate and metabolic capacity.

The efficacy of perioperative gabapentin for the treatment of postoperative pain following total knee and hip arthroplasty: a meta-analysis.

BACKGROUND: Postoperative pain after total knee arthroplasty (TKA) and total hip arthroplasty (THA) influence patients' rehabilitation and life quality. Although gabapentin has been widely used for analgesia, its efficacy is still controversial in TKA and THA. This meta-analysis was performed to assess the efficacy and safety of gabapentin following TKA and THA. METHOD: Electronic databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, MEDLINE, and ClinicalTrials.gov were comprehensively retrieved for randomized controlled trials from their inception to June 2019. A total of 7 studies, which compared the administration of gabapentin with that of placebo for the treatment of postoperative pain, were included in our meta-analysis. The meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULT: There was no difference in pain score at 24 (P = 0.87), 48 (P = 0.15), and 72 (P = 0.85) h associated with the use of gabapentin. Likewise, no difference in accumulative morphine consumption at 48 h following TKA or THA was found between gabapentin and placebo (DM = - 8.14, 95% CI - 18.55 to 2.28, P = 0.13). The incidence of opioid-related adverse effects, including nausea, pruritus, sedation, and dizziness, is no difference between gabapentin and placebo group. However, subgroup analysis indicated that gabapentin could reduce the incidence of pruritus after TKA (RR = 0.35, 95% CI 0.12 to 0.99, P = 0.05). CONCLUSION: Based on our meta-analysis, gabapentin did not decrease postoperative pain, cumulative morphine consumption, and the incidence of adverse effects after TKA and THA. There was not enough evidence to support the administrations of gabapentin for postoperative pain after TKA and THA.

Different Intra-articular Injections as Therapy for Hip Osteoarthritis: A Systematic Review and Network Meta-analysis.

PURPOSE: This systematic review and network meta-analysis aimed to compare the clinical outcomes between 4 intra-articular injections (platelet-rich plasma [PRP], hyaluronic acid [HA], corticosteroid [CS], and HA plus PRP) for hip osteoarthritis (OA). METHODS: We performed a systematic literature search in PubMed, Embase, Web of Science, and the Cochrane database through April 2018 to identify any randomized controlled trials that evaluated the clinical efficacy of HA, PRP, CS, HA-plus-PRP, and control treatments for hip OA. Baseline information-country, mean age, number of patients, and Kellgren-Lawrence grade of hip OA in the treatment and control groups-was collected. The primary outcome was the visual analog scale (VAS) score at 1, 3, 6, and 12 months after injection. RESULTS: We included 11 randomized controlled trials with a total of 1,060 patients. The Kellgren-Lawrence grades of the treatment and control groups were similar in individual studies. The pair-wise meta-analysis indicated that CS and HA were superior to the control group in reducing the VAS score at 1 month and 3 months (P < .05) and that CS was superior to HA in reducing the VAS score at 1 month (P < .05). The network meta-analysis results indicated that HA and CS exhibited a beneficial role in reducing the VAS score at 1 month. CS achieved the lowest value for the surface under the cumulative ranking curve (SUCRA) for the VAS score at 1 month (0.23), and the SUCRA values of the 5 interventions showed that PRP achieved the lowest SUCRA value for the VAS score at 6 months (0.53). CONCLUSIONS: CS injections are recommended as the most efficient agent in hip OA patients in the short term. Moreover, PRP is reported to have the highest rank for pain relief for up to 6 months. Considering the limitations of this meta-analysis, future direct comparisons with more samples are needed. LEVEL OF EVIDENCE: Level II, meta-analysis of Level I and II studies.