Research trends and hotspots of myositis ossificans: a bibliometric analysis from 1993 to 2022.

Myositis ossificans (MO) is characterized by benign heterotopic ossificans in soft tissues like muscles, which can be classified into nonhereditary MO and fibrodysplasia ossificans progressiva (FOP). Although MO has been studied for decades, no research reviewed and analyzed the features of publications in this field quantitatively and qualitatively. Using bibliometrics tools (bibliometrix R package, VOSviewer, and CiteSpace), we conducted a bibliometric analysis of 1280 articles regarding MO in the Web of Science Core Collection database from 1993 to 2022. The annual number of publications and related research areas in the MO field increased gradually in the past 20 years. The USA contributed the most percentage (42.58%) of articles. The University of Pennsylvania (UPenn) and the Journal Bone published the most articles among all institutions and journals. Kaplan FS and Shore EM from UPenn were the top two scholars who made the largest contributions to this field. Keyword analysis showed that research hotspots changed from traumatic MO and clinical management of MO to the genetic etiology, pathogenesis, and treatment of FOP. This study can provide new insights into the research trends of MO and helps researchers grasp and determine future study directions more easily.

Cooperative Catalysis-Enabled (4 + 3) Cycloaddition of 2-Indolylmethanols with In Situ-Generated ortho-Naphthoquinone Methides.

A cooperative catalysis-enabled (4 + 3) cycloaddition of 2-indolylmethanols with ortho-naphthoquinone methides (o-NQMs), which were in situ-generated from enynones, has been established in the presence of silver/Brønsted acid cocatalysts. In the reaction pathway, the key o-NQM intermediates were formed through Ag(I)-catalyzed cyclization of enynones, while the indole-based carbocation intermediates were generated via Brønsted acid-catalyzed dehydration of 2-indolylmethanols. By this approach, a wide range of seven-membered cyclohepta[b]indoles were synthesized in good yields with high efficiency under mild reaction conditions, which serves as a useful strategy toward constructing indole-fused seven-membered rings. Moreover, the catalytic asymmetric version of this (4 + 3) cycloaddition has been realized under the cooperative catalysis of Ag(I) with chiral phosphoric acid, which offered chiral cyclohepta[b]indole with a good enantioselectivity (75% ee). This work not only represents the first cooperative catalysis-enabled (4 + 3) cycloaddition of 2-indolylmethanols but also provides a good example for o-NQM-involved cycloadditions, which will contribute to the chemistry of 2-indolylmethanols and enrich the research contents of cooperative catalysis.

Association between alcohol intake and bone mineral density: results from the NHANES 2005-2020 and two-sample Mendelian randomization.

We used the data from the NHANES cross-sectional study among 14,113 participants and indicated a positive correlation between alcohol intake frequency and bone mineral density in different body sites. Mendelian randomization was conducted, and no causal relationship is significant between these two variables. The study can provide some suggestions on the daily consumption of alcohol for osteoporosis patients. PURPOSE: The effect of alcohol intake on bone mineral density (BMD) remains unclear. This study explored the association and causality between alcohol intake and BMD. METHODS: Based on the 2005-2020 National Health and Nutrition Examination Survey including 14,113 participants, we conducted co-variate-adjusted multilinear regression analyses to explore the association between alcohol intake levels and spine or femur BMD. To evaluate the causal association between alcohol intake frequency and bone mineral density, the inverse variance weighted approach of two-sample Mendelian randomization (MR) was used with genetic data from the Medical Research Council Integrative Epidemiology Unit (462,346 cases) for alcohol intake frequency and the Genetic Factors for Osteoporosis Consortium (28,496 cases) for lumbar spine and femur neck BMD (32,735 cases). RESULTS: Compared with non-drinkers, total femur BMDs but not total spine BMD increased with daily alcohol intake in males (ß = 3.63*10-2 for mild drinkers, ß = 4.21*10-2 for moderate drinkers, and ß = 4.26*10-2 for heavy drinkers). By contrast, the higher total spine BMD in females was related to higher alcohol intake levels (ß = 2.15*10-2 for mild drinkers, ß = 2.59*10-2 for moderate drinkers, and ß = 3.88*10-2 for heavy drinkers). Regarding the two-sample MR results, no causal relationship was observed between alcohol intake frequency and lumbar spine BMD (odds ratio [OR] = 1.016, P = 0.789) or femur neck BMD (OR = 1.048, P = 0.333). CONCLUSION: This study suggests a positive association between alcohol intake frequency and BMD, although the causal relationship was not significant.

Skeletal ciliopathy: pathogenesis and related signaling pathways.

Cilia are tiny organelles with conserved structures and components in eukaryotic cells. Ciliopathy is a set of diseases resulting from cilium dysfunction classified into first-order and second-order ciliopathy. With the advancement of clinical diagnosis and radiography, numerous skeletal phenotypes, including polydactyly, short limbs, short ribs, scoliosis, a narrow thorax, and numerous anomalies in bone and cartilage, have been discovered in ciliopathies. Mutation in genes encoding cilia core components or other cilia-related molecules have been found in skeletal ciliopathies. Meanwhile, various signaling pathways associated with cilia and skeleton development have been deemed to be significant for the occurrence and progression of diseases. Herein, we review the structure and key components of the cilium and summarize several skeletal ciliopathies with their presumable pathology. We also emphasize the signaling pathways involved in skeletal ciliopathies, which may assist in developing potential therapies for these diseases.

Bioinformatics and system biology analysis revealed the crosstalk between COVID-19 and osteoarthritis.

BACKGROUND: The global coronavirus disease 2019 (COVID-19) outbreak has significantly impacted public health. Moreover, there has been an association between the incidence and severity of osteoarthritis (OA) and the onset of COVID-19. However, the optimal diagnosis and treatment strategies for patients with both diseases remain uncertain. Bioinformatics is a novel approach that may help find the common pathology between COVID-19 and OA. METHODS: Differentially expressed genes (DEGs) were screened by R package "limma." Functional enrichment analyses were performed to find key biological functions. Protein-protein interaction (PPI) network was constructed by STRING database and then Cytoscape was used to select hub genes. External data sets and OA mouse model validated and identified the hub genes in both mRNA and protein levels. Related transcriptional factors (TF) and microRNAs (miRNAs) were predicted with miRTarBase and JASPR database. Candidate drugs were obtained from Drug Signatures database. The immune infiltration levels of COVID-19 and OA were evaluated by CIBERSORT and scRNA-seq. RESULTS: A total of 74 common DEGs were identified between COVID-19 and OA. Receiver operating characteristic curves validated the effective diagnostic values (area under curve > 0.7) of four hub genes (matrix metalloproteinases 9, ATF3, CCL4, and RELA) in both the training and validation data sets of COVID-19 and OA. Quantitative polymerase chain reaction and Western Blot showed significantly higher hub gene expression in OA mice than in healthy controls. A total of 84 miRNAs and 28 TFs were identified to regulate the process of hub gene expression. The top 10 potential drugs were screened including "Simvastatin," "Hydrocortisone," and "Troglitazone" which have been proven by Food and Drug Administration. Correlated with hub gene expression, Macrophage M0 was highly expressed while Natural killer cells and Mast cells were low in both COVID-19 and OA. CONCLUSION: Four hub genes, disease-related miRNAs, TFs, drugs, and immune infiltration help to understand the pathogenesis and perform further studies, providing a potential therapy target for COVID-19 and OA.

Causal effects of gut microbiota on scoliosis: A bidirectional two-sample mendelian randomization study.

Background: Recent studies have shown altered gut microbiome composition in patients with scoliosis. However, the causal effect of gut microbiota on scoliosis remains unknown. Methods: A Mendelian randomization (MR) study was conducted to quantify the impact of 191 gut microbiome taxa's instrumental variables from the MibioGen Genome-wide association study (GWAS) on scoliosis risk using data from the FinnGen GWAS (1168 cases and 16,4682 controls). Inverse variance weighted (IVW) was the main method, and MR results were verified by sensitive analysis. Results: Bilophila, Eubacterium (eligens group), Prevotella9, and Ruminococcus2 were discovered to have a protective effect on the risk of scoliosis. Ruminococcaceae UCG009, Catenibacterium, Coprococcus2, Eubacterium (ventriosum group), Lachnospiraceae (FCS020 group), Ruminiclostridium6, and Mollicutes RF9 may increase the occurrence of scoliosis. Heterogeneity (P > 0.05) and pleiotropy (P > 0.05) analysis confirmed the robustness of the MR results. Conclusion: Our study identified four protective bacteria taxa on scoliosis and seven microbiota that may increase scoliosis occurrence. Further MR analysis is required to corroborate our findings, using a more sophisticated technique to obtain estimates with less bias and greater precision or GWAS summary data with more gut microbiome and scoliosis patients.

Identification of ROCK1 as a novel biomarker for postmenopausal osteoporosis and pan-cancer analysis.

BACKGROUND: Postmenopausal osteoporosis (PMOP) is a prevalent bone disorder with significant global impact. The elevated risk of osteoporotic fracture in elderly women poses a substantial burden on individuals and society. Unfortunately, the current lack of dependable diagnostic markers and precise therapeutic targets for PMOP remains a major challenge. METHODS: PMOP-related datasets GSE7429, GSE56814, GSE56815, and GSE147287, were downloaded from the GEO database. The DEGs were identified by "limma" packages. WGCNA and Machine Learning were used to choose key module genes highly related to PMOP. GSEA, DO, GO, and KEGG enrichment analysis was performed on all DEGs and the selected key hub genes. The PPI network was constructed through the GeneMANIA database. ROC curves and AUC values validated the diagnostic values of the hub genes in both training and validation datasets. xCell immune infiltration and single-cell analysis identified the hub genes' function on immune reaction in PMOP. Pan-cancer analysis revealed the role of the hub genes in cancers. RESULTS: A total of 1278 DEGs were identified between PMOP patients and the healthy controls. The purple module and cyan module were selected as the key modules and 112 common genes were selected after combining the DEGs and module genes. Five Machine Learning algorithms screened three hub genes (KCNJ2, HIPK1, and ROCK1), and a PPI network was constructed for the hub genes. ROC curves validate the diagnostic values of ROCK1 in both the training (AUC = 0.73) and validation datasets of PMOP (AUC = 0.81). GSEA was performed for the low-ROCK1 patients, and the top enriched field included protein binding and immune reaction. DCs and NKT cells were highly expressed in PMOP. Pan-cancer analysis showed a correlation between low ROCK1 expression and SKCM as well as renal tumors (KIRP, KICH, and KIRC). CONCLUSIONS: ROCK1 was significantly associated with the pathogenesis and immune infiltration of PMOP, and influenced cancer development, progression, and prognosis, which provided a potential therapy target for PMOP and tumors. However, further laboratory and clinical evidence is required before the clinical application of ROCK1 as a therapeutic target.

Phylogeographic analysis of Siraitia grosvenorii in subtropical China provides insights into the origin of cultivated monk fruit and conservation of genetic resources.

Siraitia grosvenorii, an economically important plant species with high medicinal value, is endemic to subtropical China. To determine the population structure and origin of cultivated S. grosvenorii, we examined the variation in three chloroplast DNA regions (trnR-atpA, trnH-psbA, trnL-trnF) and two orthologous nuclear genes (CHS and EDL2) of S. grosvenorii in 130 wild individuals (selected from 13 wild populations across its natural distribution range) and 21 cultivated individuals using a phylogeographic approach. The results showed three distinct chloroplast lineages, which were restricted to different mountain ranges, and strong plastid phylogeographic structure. Our findings suggest that S. grosvenorii likely experienced ancient range expansion and survived in multiple refuges in subtropical China during glacial periods, resulting in population fragmentation in different mountainous areas. Our results also demonstrated that wild populations in Guilin (Guangxi, China) share the same gene pool as cultivated S. grosvenorii, suggesting that current cultivars were collected directly from local wild resources, consistent with the principles of "nearby domestication." The results of this study provide insights into improving the efficiency of S. grosvenorii breeding using a genetic approach and outline measures for the conservation of its genetic resources.

2-tert-Butyl-6-[(4-chloro-2-nitro-phen-yl)diazen-yl]-4-methylphenol.

In the title compound, C(17)H(18)ClN(3)O(3), the dihedral angle between the planes of the two benzene rings is 1.03 (7)°. The overall conformation of the mol-ecule is influenced, in part, by electron delocalization and by an intra-molecular bifurcated O-H⋯(O,N) hydrogen bonds. The O atoms of the nitro group, one of which serves as an H bond acceptor, are disordered over two sets of sites with refined occupancies of 0.56 (3) and 0.44 (3).