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Abstract Background/purpose(s) The gut microbiota and its metabolites play crucial roles in pathogenesis of arthritis, highlighting gut microbiota as a promising avenue for modulating autoimmunity. However, the characterization of the gut virome in arthritis patients, including osteoarthritis (OA) and gouty arthritis (GA), requires further investigation. Methods We employed virus-like particle (VLP)-based metagenomic sequencing to analyze gut viral community in 20 OA patients, 26 GA patients, and 31 healthy controls, encompassing a total of 77 fecal samples. Results Our analysis generated 6819 vOTUs, with a considerable proportion of viral genomes differing from existing catalogs. The gut virome in OA and GA patients differed significantly from healthy controls, showing variations in diversity and viral family abundances. We identified 157 OA-associated and 94 GA-associated vOTUs, achieving high accuracy in patient-control discrimination with random forest models. OA-associated viruses were predicted to infect pro-inflammatory bacteria or bacteria associated with immunoglobulin A production, while GA-associated viruses were linked to Bacteroidaceae or Lachnospiraceae phages. Furthermore, several viral functional orthologs displayed significant differences in frequency between OA-enriched and GA-enriched vOTUs, suggesting potential functional roles of these viruses. Additionally, we trained classification models based on gut viral signatures to effectively discriminate OA or GA patients from healthy controls, yielding AUC values up to 0.97, indicating the clinical utility of the gut virome in diagnosing OA or GA. Conclusion Our study highlights distinctive alterations in viral diversity and taxonomy within gut virome of OA and GA patients, offering insights into arthritis etiology and potential treatment and prevention strategies. Graphical Abstract

It is important to identify atmospheric environmental drivers of childhood asthma because asthma is the most common chronic disease in children globally. We provided an overview of the impacts of exposure to atmospheric environmental factors (e.g., meteorological factors and air pollutants) on childhood asthma, based on a series of studies with the cutting-edge environmental epidemiological methodology in Shanghai, China. Overall, we found that the prevalence of asthma among the children aged 3–7 years had increased by approximately 7 fold, from 2.1% in 1990 to 14.6% in 2019. Most meteorological factors (i.e. daily mean temperature, temperature difference, air pressure, air pressure difference, precipitation, relative humidity, sunshine and wind speed) and air pollutants (PM10, PM2.5, NO2, SO2 and O3) were significantly associated with childhood asthma (p

ABSTRACTPreeclampsia (PE), a pregnancy-specific syndrome, has been associated with the gut bacteriome. Here, to investigate the impact of the gut virome on the development of PE, we identified over 8,000 nonredundant viruses from the fecal metagenomes of 40 early-onset PE and 37 healthy pregnant women and profiled their abundances. Comparison and correlation analysis showed that PE-enriched viruses frequently connected to Blautia species enriched in PE. By contrast, bacteria linked to PE-depleted viruses were often the Bacteroidaceae members such as Bacteroides spp., Phocaeicola spp., Parabacteroides spp., and Alistipes shahii. In terms of viral function, PE-depleted viruses had auxiliary metabolic genes that participated in the metabolism of simple and complex polysaccharides, sulfur metabolism, lipopolysaccharide biosynthesis, and peptidoglycan biosynthesis, while PE-enriched viruses had a gene encoding cyclic pyranopterin monophosphate synthase, which seemed to be special, that participates in the biosynthesis of the molybdenum cofactor. Furthermore, the classification model based on gut viral signatures was developed to discriminate PE patients from healthy controls and showed an area under the receiver operating characteristic curve of 0.922 that was better than that of the bacterium-based model. This study opens up new avenues for further research, providing valuable insights into the PE gut virome and offering potential directions for future mechanistic and therapeutic investigations, with the ultimate goal of improving the diagnosis and management of PE.IMPORTANCEThe importance of this study lies in its exploration of the previously overlooked but potentially critical role of the gut virome in preeclampsia (PE). While the association between PE and the gut bacteriome has been recognized, this research takes a pioneering step into understanding how the gut virome, represented by over 8,000 nonredundant viruses, contributes to this condition. The findings reveal intriguing connections between PE-enriched viruses and specific gut bacteria, such as the prevalence of Blautia species in individuals with PE, contrasting with bacteria linked to PE-depleted viruses, including members of the Bacteroidaceae family. These viral interactions and associations provide a deeper understanding of the complex dynamics at play in PE.

Abstract Men demonstrate higher incidence and mortality rates of colorectal cancer (CRC) than women. This study aims to explain the potential causes of such sexual dimorphism in CRC from the perspective of sex‐biased gut microbiota and metabolites. The results show that sexual dimorphism in colorectal tumorigenesis is observed in both ApcMin/+ mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)‐treated mice with male mice have significantly larger and more tumors, accompanied by more impaired gut barrier function. Moreover, pseudo‐germ mice receiving fecal samples from male mice or patients show more severe intestinal barrier damage and higher level of inflammation. A significant change in gut microbiota composition is found with increased pathogenic bacteria Akkermansia muciniphila and deplets probiotic Parabacteroides goldsteinii in both male mice and pseudo‐germ mice receiving fecal sample from male mice. Sex‐biased gut metabolites in pseudo‐germ mice receiving fecal sample from CRC patients or CRC mice contribute to sex dimorphism in CRC tumorigenesis through glycerophospholipids metabolism pathway. Sexual dimorphism in tumorigenesis of CRC mouse models. In conclusion, the sex‐biased gut microbiome and metabolites contribute to sexual dimorphism in CRC. Modulating sex‐biased gut microbiota and metabolites could be a potential sex‐targeting therapeutic strategy of CRC.

Background: The purpose of this Mendelian randomization (MR) study was to assess the causal relationship between circulating cytokines and periodontitis.Materials and methods: Based on the aggregated statistics of the largest publicly available genome-wide association study (GWAS), we applied a bidirectional two-sample MR. MR analyses were conducted using Inverse variance weighted (IVW), Robust Adjusted Profile Score (RAPS), Maximum likelihood (ML), Weighted median and MR-Egger, and results obtained from IVW served as the primary outcome. Cochran Q test was used to test the heterogeneity. MR-Egger intercept test and MR polymorphism residual and outlier test (MR-PRESSO) were used for polymorphism analysis. Leave-one-out sensitivity and funnel plots were used for sensitivity analysis.Results: The IVW method indicated that interleukin 9 (IL9) had a positive causal relationship with periodontitis [odds ratio (OR) = 1.199, 95% confidence interval (CI) = 1.049–1.372, p = 0.008], and interleukin 17 (IL17) had a negative causal relationship with periodontitis (OR = 0.847, 95% CI = 0.735–0.976, p = 0.022). In bidirectional MR, periodontitis was not causally related to any of the cytokines in our study.Conclusion: Our findings provided evidence in support of potential causal associations between circulating IL9/IL17 and periodontitis.

ABSTRACT Most microbiome studies regarding the ruminant digestive tract have focused on the rumen microbiota, whereas only a few studies were performed on investigating the gut microbiota of ruminants, which limits our understanding of this important component. Herein, the gut microbiota of 30 Caprinae animals (sheep and goats) from six provinces in China was characterized using ultradeep (>100 Gbp per sample) metagenome shotgun sequencing. An inventory of Caprinae gut microbial species containing 5,046 metagenomic assembly genomes (MAGs) was constructed. Particularly, 2,530 of the genomes belonged to uncultured candidate species. These genomes largely expanded the genomic repository of the current microbes in the Caprinae gut. Several enzymes and biosynthetic gene clusters encoded by these Caprinae gut species were identified. In summary, our study extends the gut microbiota characteristics of Caprinae and provides a basis for future studies on animal production and animal health. IMPORTANCE We constructed a microbiota catalog containing 5,046 MAGs from Caprinae gut from six regions of China. Most of the MAGs do not overlap known databases and appear to be potentially new species. We also characterized the functional spectrum of these MAGs and analyzed the differences between different regions. Our study enriches the understanding of taxonomic, functional, and metabolic diversity of Caprinae gut microbiota. We are confident that the manuscript will be of utmost interest to a wide range of readers and be widely applied in future research.

Abstract. Background:. Twin pregnancies continue to increase worldwide; however, the current clinical prenatal evaluation for the intrauterine growth of twins still relies on the growth standards of singletons. We attempted to establish a set of fetal biometric references for Chinese twin pregnancies, stratified by chorionicity and conception mode as spontaneously conceived monochorionic diamniotic (SC-MCDA), spontaneously conceived dichorionic diamniotic (SC-DCDA), and assisted reproductive technology dichorionic diamniotic (ART-DCDA) twins. Methods:. From 2016 to 2019, the ultrasonographic fetal biometric measurements were longitudinally collected in pregnant women, including fetal weight, biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length. The linear mixed models were used to test the difference of growth patterns between groups, and the growth curve of each biometric parameter was modeled by a generalized additive model for location scale and shape. Results:. A total of 929 twin pregnant women and 2019 singleton pregnant women, met the inclusion criteria. Among twin pregnancies, 148 were SC-MCDA, 215 were SC-DCDA, and 566 were ART-DCDA twins. Overall, SC-DCDA twins grew faster than SC-MCDA twins, while slower than ART-DCDA twins (all P

Preeclampsia (PE) is a pregnancy complication characterized by severe hypertension and multiple organ damage. Gut microbiota has been linked to PE by previous amplicon sequencing studies. To resolve the PE gut microbiota in a higher taxonomy resolution, we performed shotgun metagenomic sequencing on the fecal samples from 40 early-onset PE and 37 healthy pregnant women. We recovered 1,750 metagenome-assembled genomes (representing 406 species) from the metagenomic dataset and profiled their abundances. We found that PE gut microbiota had enriched in some species belonging to Blautia, Pauljensenia, Ruminococcus, and Collinsella and microbial functions such as the bacitracin/lantibiotics transport system, maltooligosaccharide transport system, multidrug efflux pump, and rhamnose transport system. Conversely, the gut microbiome of healthy pregnant women was enriched in species of Bacteroides and Phocaeicola and microbial functions including the porphyrin and chlorophyll metabolism, pyridoxal-P biosynthesis, riboflavin metabolism, and folate biosynthesis pathway. PE diagnostic potential of gut microbial biomarkers was developed using both species and function profile data. These results will help to explore the relationships between gut bacteria and PE and provide new insights into PE early warning.

Background: Xanthoceraside is a component obtained in the husks of Xanthoceras sorbifolia Bunge. Series of researches proved that xanthoceraside had functions of anti-inflammation and anti-tumor effects. However, the mechanisms of xanthoceraside against bladder cancer are unclear. Accordingly, we proposed to investigate xanthoceraside's impacts and potential mechanisms in cells of bladder cancer. Methods: By using the CCK-8 assay, we measured the viability of cells. With the use of 4,6-diamidino-2-phenylindole (DAPI) staining, we examined nuclear fragmentation and chromatin condensation in the nuclei of apoptotic cells. By using flow cytometry, we measured cell apoptosis. By using Western blotting, we tested the expressions of Caspase-9, Caspase-8, Caspase-3, Bcl-xL, P53, and PI3K/Akt/Bcl-2/Bax. Results: The proliferation of cell lines of human bladder cancer T24 and 5637 was suppressed by xanthoceraside significantly in a time- and concentration-dependent way. When cell lines 5637 and T24 were incubated as the xanthoceraside dose increased, the rates of cell apoptosis were upregulated, which was dependent on dose. According to further analysis, xanthoceraside induced apoptosis by upregulating Bax and downregulating the expression of Bcl-xL and Bcl-2. However, xanthoceraside did not change the expression of Caspase-9, Caspase-8, and Caspase-3. Interestingly, xanthoceraside also downregulated the expression of p-PI3K and p-Akt, and upregulated P53. Conclusions: Xanthoceraside induces cell apoptosis through downregulation of the PI3K/Akt/Bcl-2/Bax signaling pathway in cell lines of human bladder cancer.

Environments where antibiotics are used indiscriminately exhibit microbial communities that can represent hot-spots of resistance gene enrichment, which in turn could spread to humans. Here, the authors characterize how exposure to swine farms environment lead to temporal changes in the gut microbiome and resistome of healthy veterinary students.

Background: Imbalances in gut microbiota composition are linked to hypertension, host metabolic abnormalities, systemic inflammation, and other conditions. In the present study, we examined the changes of gut microbiota in women with early-onset preeclampsia (PE) and in normotensive, uncomplicated pregnant women during late pregnancy and at 1 and 6 weeks postpartum.Methods: Gut microbiota profiles of women with PE and healthy pregnant women in the third trimester and at 1 and 6 weeks postpartum were assessed by 16S rRNA gene amplicon sequencing. Plasma levels of interleukin-6 (IL-6), intestinal fatty acid-binding protein (I-FABP), zonulin, and lipopolysaccharide (LPS) were measured in the third trimesters.Results: At the genus level, 8 bacterial genera were significantly enriched in the antepartum samples of PE patients compared to healthy controls, of which Blautia, Ruminococcus2, Bilophila, and Fusobacterium represented the major variances in PE microbiomes. Conversely, 5 genera, including Faecalibacterium, Gemmiger, Akkermansia, Dialister, and Methanobrevibacter, were significantly depleted in antepartum PE samples. Maternal blood pressure and liver enzyme levels were positively correlated to the PE-enriched genera such as Anaerococcus, Ruminococcus2, Oribacterium, and Bilophila, while the fetal features (e.g., Apgar score and newborn birth weight) were positively correlated with PE-depleted genera and negatively correlated with PE-enriched genera. Moreover, maternal blood IL-6 level was positively associated with gut Bilophila and Oribacterium, whereas LPS level was negatively associated with Akkermansia. In terms of postpartum women, both the gut microbial composition and the PE-associated microbial alterations were highly consistent with those of the antepartum women.Conclusion: PE diagnosed in the third trimester of pregnancy is associated with a disrupted gut microbiota composition compared with uncomplicated pregnant women, which are associated with maternal clinical features (blood pressure level and liver dysfunction) and newborn birth weight. Moreover, these antepartum alterations in gut microbiota persisted 6 weeks postpartum.

A simple, convenient and efficient synthesis for a series of crown ether functionalized imidazoles from benzo-15-crown-5 (B15C5), benzo-18-crown-6 (B18C6), imidazole (Im), 2-methylimidazole (mIm), benzimidazole (bIm) and 2-methyl benzimidazole (mbIm) is reported. All these compounds obtained were characterized by IR, 1H NMR, ESI-MS and elemental analysis.

A series of pyrido[2,3-d]pyrimidine derivatives were synthesized by the three-component reaction of aromatic aldehyde, malononitrile and 6-amino-4-hydroxy-2-mercaptopyrimidine catalyzed by sodium lauryl sulfate (SDS) in aqueous media. It was interesting that further aromatization took place automatically. This method provides several advantages such as easier work-up, milder reaction conditions and environmental friendly.

BackgroundSeveral existing studies have shown a correlation between some of the blood and urine biomarkers and oral leukoplakia (OLK). However, the causality of this relationship remains uncertain. Thus, this study aimed to examine the causal association between 35 blood and urine biomarkers and OLK.MethodsSingle nucleotide polymorphisms (SNPs) associated with 35 blood and urine biomarkers were selected as instrumental variables (IVs) using a two-sample Mendelian randomization(MR) study to assess the causal relationship between the biomarkers and the risk of oral leukoplakia. We used the inverse variance weighted (IVW) method as the main analysis. Furthermore, several sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy, and stability.ResultsBased on the selection criteria of the Inverse Variance Weighted (IVW) method, the analysis found that 5 blood and urine biomarkers were significantly associated with the development of leukoplakia, of which the results of IVW showed that abnormalities of Apolipoprotein B (Apo B), Cholesterol, Low-density Lipoprotein (LDL), Triglycerides (TG) promoted the development of oral leukoplakia, and Non Albumin Protein (NAP) had a protective effect on the development of oral leukoplakia. We then performed a Bonferroni correction for these results, and after correction Apo B was still causally associated with the development of oral leukoplakia (IVW P

AIM: To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) compared to those of PPV with subsequent cataract surgery. METHODS: This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR, aged >45y, with mild cataracts. The participants were randomly assigned to the combined (PPV combined with simultaneously cataract surgery, i.e., phacovitrectomy) or subsequent (PPV with subsequent cataract surgery 6mo later) group and followed up for 12mo. The primary outcome was the change in best-corrected visual acuity (BCVA) from baseline to 6mo, and the secondary outcomes included complication rates and medical expenses. RESULTS: In total, 129 patients with PDR were recruited and equally randomized (66 and 63 in the combined and subsequent groups respectively). The change in BCVA in the combined group [mean, 36.90 letters; 95% confidence interval (CI), 30.35–43.45] was significantly better (adjusted difference, 16.43; 95%CI, 8.77–24.08; P

A series of nanosized cavity-containing bipyrazolate-bridge metallomacrocycles with dimetal centers are synthesized through a directed self-assembly approach involving spontaneous deprotonation of the 1H-bipyrazolyl ligands in aqueous solution. The complexes have weak Pd(II)...Pd(II) or Pt(II)...Pt(II) interactions are characterized by elemental analysis (super 1)H and (super 13)C, NMR, cold-spray ionization or electrospray ionization mass spectrometry, UV-visible spectroscopy and luminesescence spectroscopy.

Superior capsular reconstruction is a common treatment option for irreparable rotator cuffs. Arthroscopic surgery procedures mostly use anchor-based methods. However, difficulty in preoperative graft measurement and intra-articular knot-tying present an obstacle for most sport surgeons. Complementing the known advantages of the transosseous technique in rotator cuff repair, a feasible, economical arthroscopic transosseous superior capsular reconstruction technique is described in this Technical Note. This procedure results not only in similar fixation strength and stability and greater bone stock but also in greater cost effectiveness due to using fewer anchors. This Technical Note describes the procedure in detail and compares it with conventional procedures.

Abstract Background For treating distal femur fractures, minimally invasive plating techniques with indirect reduction of the metadiaphysis while minimizing the damage to the peripheral soft tissue has gradually become the standard. However, all the current approaches use a straight or lazy curved incision adjacent to the patella or along the lateral side of the femur, which allows for easier proximal extension but increases the incision length. Methods In order to achieve a more physiological and esthetic outcome while leaving the metadiaphysis untouched, we developed an approach using a lambda-shaped incision, which sacrifices the potential for proximal extension but preserves much more peripheral soft tissue. Here, we describe our technique and our experience with it in 19 patients (12 men and 7 women). Results Fractures healing by first intention was observed in all patients. The postoperative knee range of motion can reach up to 90° in most of the patient. Clinically, 9 patients had excellent results, 6 had good results, 3 had fair results, and 2 had loss of follow-up. Conclusions Our minimally invasive lambda-incision approach allows sufficient visual access to almost the entire joint surface, including the entire lateral femoral condyle, trochlear surface, and distal medial condyle, where reduction is required. The lambda incision provides a much larger window than that offered by a same-length straight incision. The vertical turn at the mid-patellar level parallels the skin crease and geniculate artery, reducing soft tissue damage and resulting in a smooth healing wound. Moreover, plate and distal screw insertion is easier than that through a straight incision. Because the metadiaphysis region is mostly left untouched, ideal fracture-healing environment is preserved.

Abstract Background The fabella is a sesamoid bone in the posterolateral capsule of the human knee joint. In quadrupedal mammals, the fabella is believed to have a role similar to the patella in redirecting extension forces of the knee joint from one point to another. In bipeds, the fabella is not touching the back of the bent knee, and therefore the role in redirecting forces declines. Posterolateral knee pain can be associated with the irritation between the fabella and lateral femoral condyle, a phenomenon also known as fabella syndrome. In cases that are unresponsive to conservative management, surgical fabellectomy can be a successful treatment option. Among the surgical approaches, open resection is most commonly seen. There are also literature reporting arthroscopic-assisted open resection, but seldom mentioned the all-arthroscopic fabellectomy. Case presentation We present 3 patients with a long history (> 12 month) of posterolateral knee pain under suspicion of different pain origins. The diagnosis of fabella impingement was eventually made by ruling out of other causes. All the patients underwent all-arthroscopic fabellectomy for diagnosis and treatment. Investigations of the resected fabella suggested chronic impingement with apparent osteophyte formation and cartilage wearing of the articular side. All patients have been continually followed up at our outpatient department and reported to be pain free after the procedure. Conclusions In the patients presenting posterolateral pain, fabella syndrome cannot be ignored due to its relative higher presence in Asian population. In our experience, the all-arthroscopic fabellectomy offers a smaller wound size, less post-operative pain, fewer days of hospitalization and quicker time to rehabilitation for the patients with chronic posterolateral knee pain caused by fabella syndrome.