Gelatin/Dopamine/Zinc-Doped Ceria/Curcumin nanocomposite hydrogels for repair of chronic refractory wounds.

Chronic wound healing is a common clinical challenge, characterized by bacterial infection, protracted inflammatory response, oxidative stress, and insufficient neovascularization. Nanozymes have emerged as a promising solution for treating skin wounds due to their antioxidant, antibacterial, and angiogenic properties. In recent years, combining nanozymes with hydrogels to jointly promote wound healing has attracted increasing research interest. However, most of the current nanocomposite hydrogels are still not effective in simultaneously controlling inflammatory, oxidative stress and bacterial invasion in wound healing. Improving the therapeutic functional diversity and efficacy of nanocomposite hydrogels remains a problem that needs to be addressed. In this study, we prepared nanocomposite hydrogels (GelMD-Cur@ZHMCe) by combining methylacrylated gelatin modified with dopamine (GelMD) with Zinc-doped hollow mesoporous cerium oxide nanoparticles loaded with curcumin (Cur@ZHMCe). The resulting hydrogels exhibited excellent water absorption, adhesion, and biocompatibility. In vitro and in vivo studies have demonstrated that GelMD-Cur@ZHMCe has excellent antioxidant, antibacterial, anti-inflammatory and vasculature-promoting properties, which enable it to rapidly promote wound repair. The wound healing rate of the rat total skin defect infection model treated with GelMD-Cur@ZHMCe reached 98.5±4.9 % after 14 days of treatment. It was demonstrated that this multifunctional nanocomposite hydrogel provides a promising therapeutic strategy for skin repair.

Curcumenol regulates Histone H3K27me3 demethylases KDM6B affecting Succinic acid metabolism to alleviate cartilage degeneration in knee osteoarthritis.

BACKGROUND: Cartilage metabolism dysregulation is a crucial driver in knee osteoarthritis (KOA). Modulating the homeostasis can mitigate the cartilage degeneration in KOA. Curcumenol, derived from traditional Chinese medicine Curcuma Longa L., has demonstrated potential in enhancing chondrocyte proliferation and reducing apoptosis. However, the specific mechanism of Curcumenol in treating KOA remains unclear. This study aimed to demonstrate the molecular mechanism of Curcumenol in treating KOA based on the transcriptomics and metabolomics, and both in vivo and in vitro experimental validations. MATERIALS AND METHODS: In this study, a destabilization medial meniscus (DMM)-induced KOA mouse model was established. And the mice were intraperitoneally injected with Curcumenol at 4 and 8 mg/kg concentrations. The effects of Curcumenol on KOA cartilage and subchondral was evaluated using micro-CT, histopathology, and immunohistochemistry (IHC). In vitro, OA chondrocytes were induced with 10 µg/mL lipopolysaccharide (LPS) and treated with Curcumenol to evaluate the proliferation, apoptosis, and extracellular matrix (ECM) metabolism through CCK8 assay, flow cytometry, and chondrocyte staining. Furthermore, transcriptomics and metabolomics were utilized to identify differentially expressed genes (DEGs) and metabolites. Finally, integrating multi-omics analysis, virtual molecular docking (VMD), and molecular dynamics simulation (MDS), IHC, immunofluorescence (IF), PCR, and Western blot (WB) validation were conducted to elucidate the mechanism by which Curcumenol ameliorates KOA cartilage degeneration. RESULTS: Curcumenol ameliorated cartilage destruction and subchondral bone loss in KOA mice, promoted cartilage repair, upregulated the expression of COL2 while downregulated MMP3, and improved ECM synthesis metabolism. Additionally, Curcumenol also alleviated the damage of LPS on the proliferation activity and suppressed apoptosis, promoted ECM synthesis. Transcriptomic analysis combined with weighted gene co-expression network analysis (WGCNA) identified a significant downregulation of 19 key genes in KOA. Metabolomic profiling showed that Curcumenol downregulates the expression of d-Alanyl-d-alanine, 17a-Estradiol, Glutathione, and Succinic acid, while upregulating Sterculic acid and Azelaic acid. The integrated multi-omics analysis suggested that Curcumenol targeted KDM6B to regulate downstream protein H3K27me3 expression, which inhibited methylation at the histone H3K27, consequently reducing Succinic acid levels and improving KOA cartilage metabolism homeostasis. Finally, both in vivo and in vitro findings indicated that Curcumenol upregulated KDM6B, suppressed H3K27me3 expression, and stimulated collagen II expression and ECM synthesis, thus maintaining cartilage metabolism homeostasis and alleviating KOA cartilage degeneration. CONCLUSION: Curcumenol promotes cartilage repair and ameliorates cartilage degeneration in KOA by upregulating KDM6B expression, thereby reducing H3K27 methylation and downregulating Succinic Acid, restoring metabolic stability and ECM synthesis.

Molecular epidemiology, genetic diversity, antibiotic resistance and pathogenicity of Stenotrophomonas maltophilia complex from bacteremia patients in a tertiary hospital in China for nine years.

Background: The Stenotrophomonas maltophilia complex (Smc) has emerged as a significant nosocomial pathogen contributing to increased mortality rates, particularly in case of bloodstream infections. Methods: This study employed whole-genome sequencing (WGS) to assess the genetic diversity, antimicrobial resistance profiles, molecular epidemiology and frequencies of virulence genes among 55 S. maltophilia isolates obtained from bacteremic cases over a 9-year period. Results: Based on the threshold of 95% average nucleotide identity (ANI) and 70% digital DNA-DNA hybridization (dDDH) for genospecies delineation, we classified 37 isolates into 6 known species, all belonging to the Smc. The remaining 18 isolates sequenced in this study were assigned to 6 new genomospecies. Among the 55 isolates, we identified 44 different sequence types (STs), comprising 22 known and 22 novel allele combinations. The resistance rate of Smc against trimethoprim-sulfamethoxazole (TMP/SMX) was found to be 3.6%, with the sul1 and class one integron integrase genes (intI) detected in these isolates. All Smc isolates were susceptible to minocycline. Furthermore, all Smc strains harbored the motA, pilU, smf-1 and Stmpr2 genes. Genomospecies 1 (100%, n = 9), Stenotrophomonas maltophilia (84.21%, n = 19) and Stenotrophomonas sepilia (71.43%, n = 7) demonstrated a higher percentage of the afaD gene, which was also associated with a higher separation rate. In addition to motA, pilU, smf-1, and Stmpr2 genes, all S. maltophilia strains (100%) contained entA, gspD, KatA, and stmPr1 genes, while all genomospecies 1 strains (100%) contained afaD, entA, gspD, and KatA genes. Conclusion: Our study highlights the genetic diversity among Smc isolates from patients with bacteremia, revealing 22 novel ST types, 58 new alleles and 6 new genomospecies. S. maltophilia and S. pavanii were found to carry more virulence factors, emphasizing the importance of accurate strain identification. Minocycline emerged as a promising alternative antibiotic for patients who were resistant to TMP/SMX.

A new isopropyl esterification method for quantitative profiling of short-chain fatty acids in human and cow milk by gas chromatograph-mass spectrometer.

Short-chain fatty acids (SCFA) content in milk may have been underestimated due to the neglect of the esterified SCFA content and the lack of an accurate detection method, especially for C1:0, C2:0, and C3:0 SCFA. In this study, an accurate GC-MS profiling method was established for 10 SCFA. A 2-step esterification, including alkaline saponification (60°C for 30 min) and acid-catalyzed esterification (80°C for 150 min) in water/isopropyl/hexane (1:2:1, volume ratio), was found to be the most suitable for the quantification of esterified and nonesterified SCFA analysis. The validation results demonstrate satisfactory linearity, sensitivity, matrix effects, precision, and accuracy. The recoveries of nonesterified and esterified SCFA ranged from 82.78% to 112.49%, respectively. Human milk is distinguished from cow milk by its higher C1:0 and C2:0 content and lower C4:0 and C6:0 content. This method successfully accomplished qualitative and quantitative estimation of all 10 SCFA in milk, including both nonesterified and esterified SCFA. Furthermore, whether our method is applicable for the determination of SCFA in serum, rumen fluid, and feces remains to be explored.

Genome sequence-based species classification of Enterobacter cloacae complex: a study among clinical isolates.

Accurate species-level identification of Enterobacter cloacae complex (ECC) is crucial for related research. The classification of ECC is based on strain-to-strain phylogenetic congruence, as well as genomic features including average nucleotide identity (ANI) and digitalized DNA-DNA hybridization (dDDH). ANI and dDDH derived from whole-genome sequencing have emerged as a reliable metric for assessing genetic relatedness between genomes and are increasingly recognized as a standard for species delimitation. Up to now, there are two different classification methods for ECC. The first one categorizes E. hormaechei, a species within ECC, into five subspecies (E. hormaechei subsp. steigerwaltii, subsp. oharae, subsp. xiangfangensis, subsp. hoffmannii, and subsp. hormaechei). The second classifies E. hormaechei as three species: E. hormaechei, "E. xiangfangensis," "E. hoffmanii." While the former is well-accepted in the academic area, the latter may have a greater ability to distinguish different species of ECC. To assess the suitability of these identification criteria for clinical ECC isolates, we conducted a comprehensive analysis involving phylogenetic analysis, ANI and dDDH value alignment, virulence gene identification, and capsule typing on 256 clinical ECC strains isolated from the bloodstream. Our findings indicated that the method of categorizing E. hormaechei into five subspecies has better correlation and consistency with the molecular characteristics of clinical ECC isolates, as evidenced by phylogenetic analysis, virulence genes, and capsule typing. Therefore, the subspecies-based classification method appears more suitable for taxonomic assignments of clinical ECC isolates. IMPORTANCE: Standardizing taxonomy of the Enterobacter cloacae complex (ECC) is necessary for data integration across diverse studies. The study utilized whole-genome data to accurately identify 256 clinical ECC isolated from bloodstream infections using average nucleotide identity (ANI), digitalized DNA-DNA hybridization (dDDH), and phylogenetic analysis. Through comprehensive assessments including phylogenetic analysis, ANI and dDDH comparisons, virulence gene, and capsule typing of the 256 clinical isolates, it was concluded that the classification method based on subspecies exhibited better correlation and consistency with the molecular characteristics of clinical ECC isolates. In summary, this research contributes to the precise identification of clinical ECC at the species level and expands our understanding of ECC.

It is time to move forward: a bibliometric analysis of top 50 cited articles in elbow arthroscopy.

OBJECTIVES: To analyze the bibliometric characteristics of the top 50 cited articles in elbow arthroscopy. METHODS: The Web of Science Core Collection was employed to systematically retrieve publications related to elbow arthroscopy. Subsequently, the top 50 cited articles meeting the predefined inclusion criteria were meticulously documented and subjected to comprehensive bibliometric analysis. RESULTS: The top 50 cited articles spanned the years 1999-2017, with the 2010s emerging as the most prolific decade. Citations per article varied from 24 to 211, and citation density ranged from 1.61 to 9.17. The United States dominated in article production and citations. Predominantly, the articles took the form of case series and expert opinions, with a notable absence of level I or II evidence. The keywords with the highest frequencies were "arthrofibrosis," "complications," and "release." These keywords formed five main clusters: stiff elbow, osteoarthritis, osteochondritis dissecans, and lateral epicondylitis. CONCLUSIONS: The majority of the top 50 cited articles in elbow arthroscopy comprised case series exhibiting Level IV or V evidence. Despite a dynamic development post-2010, elbow arthroscopy articles showed lower mean citations and citation density compared to other joints, potentially influenced by concerns about complications. However, with the increasing prevalence of elbow arthroscopy procedures, it is anticipated that higher-level articles, particularly those focusing on complications and exploring additional indications, will supersede some of the articles included in this analysis. LEVEL OF EVIDENCE: IV.

A Multifunctional Nanozyme Integrating Antioxidant, Antimicrobial and Pro-Vascularity for Skin Wound Management.

Background: Skin wounds are a prevalent issue that can have severe health consequences if not treated correctly. Nanozymes offer a promising therapeutic approach for the treatment of skin wounds, owing to their advantages in regulating redox homeostasis to reduce oxidative damage and kill bacteria. These properties make them an effective treatment option for skin wounds. However, most of current nanozymes lack the capability to simultaneously address inflammation, oxidative stress, and bacterial infection during the wound healing process. There is still great potential for nanozymes to increase their therapeutic functional diversity and efficacy. Methods: Herein, copper-doped hollow mesopores cerium oxide (Cu-HMCe) nanozymes with multifunctional of antioxidant, antimicrobial and pro-vascularity is successfully prepared. Cu-HMCe can be efficiently prepared through a simple and rapid solution method and displays sound physiological stability. The biocompatibility, pro-angiogenic, antimicrobial, and antioxidant properties of Cu-HMCe were assessed. Moreover, a full-thickness skin defect infection model was utilized to investigate the wound healing capacity, as well as anti-inflammatory and pro-angiogenic properties of nanozymes in vivo. Results: Both in vitro and in vivo experiments have substantiated Cu-HMCe's remarkable biocompatibility. Moreover, Cu-HMCe possesses potent antioxidant enzyme-like catalytic activity, effectively clearing DPPH radicals (with a scavenging rate of 80%), hydroxyl radicals, and reactive oxygen species. Additionally, Cu-HMCe exhibits excellent antimicrobial and pro-angiogenic properties, with over 70% inhibition of both E. coli and S. aureus. These properties collectively promote wound healing, and the wound treated with Cu-HMCe achieved a closure rate of over 90% on the 14th day. Conclusion: The results indicate that multifunctional Cu-HMCe with antioxidant, antimicrobial, and pro-angiogenic properties was successfully prepared and exhibited remarkable efficacy in promoting wound healing. This nanozymes providing a promising strategy for skin repair.

Research and publication trends on knee osteoarthritis and cellular senescence: a bibliometric analysis.

Background: Cellular senescence is associated with age-related pathological changes, senescent cells promote the development of knee osteoarthritis. A better understanding between knee osteoarthritis and cellular senescence may enhance the effectiveness of therapies that aim to slow or stop the progression of this disease. Purpose: This study aimed to systematically analyze and visualize the publication trends, research frontiers and current research hotspots of knee osteoarthritis and cellular senescence by using bibliometrics. Methods: The publication search was performed on the Web of Science Core Collection database for documents published from 1992 to 2023. VOSviewer, Citespace, R package Bibliometrix and Microsoft Office Excel were used to study the characteristics of the publications. The publication number, countries, institutions, authors, journals, citations and co-citations, keywords were analyzed. Results: A total of 1,074 publications were analyzed, with an average annual growth rate of 29.89%. United States accounted for the biggest contributor, ranked first in publications and citations. Publications of this field were published in 420 journals, OSTEOARTHRITIS and CARTILAGE was the most influential. A total of 5,657 authors contributed to this research. The most productive author was Lotz, MK (n = 31, H-index = 22, Total citation = 2,619), followed by Loeser, R.F (n = 16, H-index = 14, Total citation = 2,825). However, the collaboration between authors was relatively weak. Out of the 1,556 institutions involved, 60% were from the United States. Scripps Research ranked first with 25 papers and a total of 2,538 citations. The hotspots of this field had focused on the pathomechanisms (e.g., expression, inflammation, apoptosis, autophagy, oxidative stress) and therapeutics (e.g., stem cell, platelet-rich plasma, transplantation, autologous chondrocytes, repair), and the exploration of Senolytics might be the important direction of future research. Conclusion: Research on the cross field of knee osteoarthritis and cellular senescence is flourishing. Age-related pathomechanism maps of various cells in the joint and the targeted medicines for the senescent cells may be the future trends. This bibliometric study provides a comprehensive analysis of this cross field and new insights into future research.

Age-dependent dendrobine biosynthesis in Dendrobium nobile: insights into endophytic fungal interactions.

Introduction: Dendrobium nobile (D. nobile), a valued Chinese herb known for its diverse pharmacological effects, owes much of its potency to the bioactive compound dendrobine. However, dendrobine content varies significantly with plant age, and the mechanisms governing this variation remain unclear. This study delves into the potential role of endophytic fungi in shaping host-microbe interactions and influencing plant metabolism. Methods: Using RNA-seq, we examined the transcriptomes of 1-year-old, 2-year-old, and 3-year-old D. nobile samples and through a comprehensive analysis of endophytic fungal communities and host gene expression in D. nobile stems of varying ages, we aim to identify associations between specific fungal taxa and host genes. Results: The results revealing 192 differentially expressed host genes. These genes exhibited a gradual decrease in expression levels as the plants aged, mirroring dendrobine content changes. They were enriched in 32 biological pathways, including phagosome, fatty acid degradation, alpha-linolenic acid metabolism, and plant hormone signal transduction. Furthermore, a significant shift in the composition of the fungal community within D. nobile stems was observed along the age gradient. Olipidium, Hannaella, and Plectospherella dominated in 1-year-old plants, while Strelitziana and Trichomerium prevailed in 2-year-old plants. Conversely, 3-year-old plants exhibited additional enrichment of endophytic fungi, including the genus Rhizopus. Two gene expression modules (mediumpurple3 and darkorange) correlated significantly with dominant endophytic fungi abundance and dendrobine accumulation. Key genes involved in dendrobine synthesis were found associated with plant hormone synthesis. Discussion: This study suggests that the interplay between different endophytic fungi and the hormone signaling system in D. nobile likely regulates dendrobine biosynthesis, with specific endophytes potentially triggering hormone signaling cascades that ultimately influence dendrobine synthesis.

Exploring molecular mechanisms underlying the pathophysiological association between knee osteoarthritis and sarcopenia.

Objectives: Accumulating evidence indicates a strong link between knee osteoarthritis (KOA) and sarcopenia. However, the mechanisms involved have not yet been elucidated. This study primarily aims to explore the molecular mechanisms that explain the connection between these 2 disorders. Methods: The gene expression profiles for KOA and sarcopenia were obtained from the Gene Expression Omnibus database, specifically from GSE55235, GSE169077, and GSE1408. Various bioinformatics techniques were employed to identify and analyze common differentially expressed genes (DEGs) across the 3 datasets. The techniques involved the analysis of Gene Ontology and pathways to enhance understanding, examining protein-protein interaction (PPI) networks, and identifying hub genes. In addition, we constructed the network of interactions between transcription factors (TFs) and genes, the co-regulatory network of TFs and miRNAs for hub genes, and predicted potential drugs. Results: In total, 14 common DEGs were found between KOA and sarcopenia. Detailed information on biological processes and signaling pathways of common DEGs was obtained through enrichment analysis. After performing PPI network analysis, we discovered 4 hub genes (FOXO3, BCL6, CDKN1A, and CEBPB). Subsequently, we developed coregulatory networks for these hub genes involving TF-gene and TF-miRNA interactions. Finally, we identified 10 potential chemical compounds. Conclusions: By conducting bioinformatics analysis, our study has successfully identified common gene interaction networks between KOA and sarcopenia. The potential of these findings to offer revolutionary understanding into the common development of these 2 conditions could lead to the identification of valuable targets for therapy.

Relationship between rumen bacterial community and milk fat in dairy cows.

Introduction: Milk fat is the most variable nutrient in milk, and recent studies have shown that rumen bacteria are closely related to milk fat. However, there is limited research on the relationship between rumen bacteria and milk fatty. Fatty acids (FAs) are an important component of milk fat and are associated with various potential benefits and risks to human health. Methods: In this experiment, forty-five healthy Holstein dairy cows with alike physiological and productive conditions were selected from medium-sized dairy farms and raised under the same feeding and management conditions. The experimental period was two weeks. During the experiment, raw milk and rumen fluid were collected, and milk components were determined. In this study, 8 high milk fat percentage (HF) dairy cows and 8 low milk fat percentage (LF) dairy cows were selected for analysis. Results: Results showed that the milk fat percentage in HF group was significantly greater than that of the dairy cows in the LF group. 16S rRNA gene sequencing showed that the rumen bacterial abundance of HF dairy cows was significantly higher than that in LF dairy cows; at the genus level, the bacterial abundances of Prevotellaceae_UCG-001, Candidatus_Saccharimonas, Prevotellaceae_UCG-003, Ruminococcus_1, Lachnospiraceae_XPB1014_group, Lachnospiraceae_AC2044_group, probable_genus_10 and U29-B03 in HF group were significantly higher than those in the LF group. Spearman rank correlation analysis indicated that milk fat percentage was positively related to Prevotellaceae_UCG-001, Candidatus_Saccharimonas, Prevotellaceae_UCG-003, Ruminococcus_1, Lachnospiraceae_XPB1014_group, Lachnospiraceae_AC2044_group, probable_genus_10 and U29-B03. Furthermore, Prevotellaceae_UCG-001 was positively related to C14:0 iso, C15:0 iso, C18:0, Ruminococcus_1 with C18:1 t9, Lachnospiraceae_AC2044_group with C18:1 t9 and C18:1 t11, U29-B03 with C15:0 iso. Discussion: To sum up, rumen bacteria in dairy cows are related to the variation of milk fat, and some rumen bacteria have potential effects on the deposition of certain fatty acids in raw milk.

Species of associated bryophytes and their effects on the yield and quality of Dendrobium nobile.

BACKGROUND: Dendrobium nobile has unique growth environment requirements, and unstable yields and high management costs are the key factors restricting the development of its imitation wild cultivation industry. The present study explored the effects of different associated bryophyte species on the yield and quality of D. nobile to clarify the dominant bryophyte species associated with D. nobile and to provide a scientific basis for the rational cultivation and quality evaluation of D. nobile. RESULTS: The growth of D. nobile was closely related to the microenvironment of the Danxia stone, and the different associated bryophytes had different effects on D. nobile growth. There was a rich variety of bryophytes associated with D. nobile, with a total of 15 families, 24 genera and 31 species of bryophytes identified in the study area, including 13 families, 22 genera and 29 species of mosses and 2 families, 2 genera and 2 species of liverworts, and mosses predominated in the association with D. nobile. Usually, 3-9 species of bryophytes were growing in association with D. nobile, among which associations of 5-6 bryophytes species were more common, and the bryophytes associated with D. nobile were only related to the species to which they belonged. The dry matter accumulation, quality and mineral content of D. nobile differed significantly among different bryophyte species. The coefficients of variation of dry matter accumulation, dendrobine content and content of 11 mineral elements of D. nobile in the 35 sample quadrats were 25.00%, 21.08%, and 11.33-57.96%, respectively. The biomass, dendrobine content and mineral content of D. nobile were analysed by principal component analysis (PCA) and membership function. The results showed that each evaluation method initially screened Trachycystis microphylla and Leucobryum juniperoideum as the dominant associated bryophytes in the preliminary identification analysis, and the frequency of occurrence and coverage of the two bryophytes were significantly higher than those of the remaining bryophytes. It was determined that T. microphylla and L. juniperoideum were the dominant associated bryophytes. CONCLUSIONS: There is a rich variety of bryophytes associated with D. nobile. The yield and quality of D. nobile differed significantly among different bryophyte species. T. microphylla and L. juniperoideum were the dominant associated bryophytes, and were the two bryophytes associated with D. nobile through mixed growth.

In vitro Antimicrobial Activity and Dose Optimization of Eravacycline and Other Tetracycline Derivatives Against Levofloxacin-Non-Susceptible and/or Trimethoprim-Sulfamethoxazole-Resistant Stenotrophomonas maltophilia.

Purpose: To better guide clinical use, we determined the in vitro antimicrobial activity of the new drug eravacycline and other tetracycline derivatives against levofloxacin (LVFX)-non-susceptible and/or trimethoprim-sulfamethoxazole (TMP-SMZ)-resistant Stenotrophomonas maltophilia and evaluated their dosing regimens. Methods: Seventy-seven unique strains of S. maltophilia were isolated from sputa samples and airway aspirate samples that were either LVFX-non-susceptible and/or TMP-SMZ-resistant. Monte Carlo simulations were performed for different dosing regimens according to the population pharmacokinetic parameters of antibiotics in patients with respiratory tract infections at the minimum inhibitory concentration (MIC). Results: Eravacycline had excellent in vitro antibacterial activity against LVFX-non-susceptible and/or TMP-SMZ-resistant S. maltophilia. Monte Carlo simulations showed that for LVFX-non-susceptible strains, the cumulative fraction of response (CFR) of minocycline at the conventional recommended dose of 100 mg q12 h was 90.90%; for TMP-SMZ-resistant strains, the CFR of minocycline at a high dose of 200 mg q12 h was only 91.64%. For strains resistant to both LVFX and TMP-SMZ, the CFR of minocycline at a high dose of 200 mg q12 h was 89.81%. In contrast, the CFR of tigecycline was less than 40%, even at a dose of 100 mg q12 h. Conclusion: For pneumonia, minocycline is better for S. maltophilia that is non-susceptible to LVFX; for TMP-SMZ-resistant strains and strains that are not susceptible to either LVFX or TMP-SMZ, the efficiency of eravacycline requires further evaluation. Eravacycline may be a better choice for extremely resistant S. maltophilia strains that are non-susceptible to LVFX, TMP-SMZ, and minocycline.

Causal relationship between sarcopenia and osteoarthritis: a bi-directional two-sample mendelian randomized study.

BACKGROUND: Previous studies have shown that osteoarthritis (OA) and sarcopenia (SP) are closely related to each other, but the causal relationships between them have not been established. The aim of this study was to investigate the causal associations between OA and SP via a bi-directional Mendelian randomization (MR) approach. METHODS: A bi-directional two-sample MR was adopted to research the causal relationship between SP and OA. The instrumental variables for SP and four types of OA: KOA, HOA, total knee replacement (TKR) and total hip replacement (THR) were derived from published large genome-wide association studies (GWAS). The inverse variance weighted (IVW), MR-Egger and weighted median estimator (WME) methods were used to estimate bi-directional causal effects. RESULTS: Low grip strength (GS) did not have a causal effect on four types of OA (KOA: OR = 1.205, 95% CI 0.837-1.734, p = 0.316; HOA: OR = 1.090, 95% CI 0.924-1.609, p = 0.307; TKR: OR = 1.190, 95% CI 1.084-1.307, p = 0.058; THR: OR = 1.035, 95% CI 0.792-1.353, p = 0.798), while appendicular lean mass (ALM) had a causal effect on four types of OA (KOA: OR = 1.104, 95% CI 1.041-1.171, p = 0.001; HOA: OR = 1.151, 95% CI 1.071-1.237, p < 0.001; TKR: OR = 1.114, 95% CI 1.007-1.232, p < 0.001; THR: OR = 1.203, 95% CI 1.099-1.316, p < 0.001). In the reverse direction, KOA or HOA did not have a significant causal effect on both GS and ALM (KOA-GS: OR = 1.077, 95% CI 0.886-1.309, p = 0.458; KOA-ALM: Beta = 0.004, p = 0.892; HOA-GS: OR = 1.038, 95% CI 0.981-1.099, p = 0.209; HOA-ALM: Beta = - 0.017, p = 0.196; TKR-GS: OR = 0.999, 95% CI 0.739-1.351, p = 0.997; TKR-ALM: Beta = 0.018, p = 0.501; THR-GS: OR = 1.037, 95% CI 0.978-1.101, p = 0.222; THR-ALM: Beta = - 0.023, p = 0.081). CONCLUSIONS: The present study suggests that SP may have a causal effect on OA through changes in muscle composition rather than muscle strength, while little evidence was provided for the causal effect of OA on SP.

Posterior Olecranon Fracture Dislocations in Adults: A Systematic Review.

Posterior olecranon fracture dislocations (POFDs) were considered posterior Monteggia lesions, which were less described in the literature. The purpose of this study was to provide a systematic review of the diagnosis, treatment, prognosis, and complications of POFDs in adults. A systematic review was performed to identify all relevant studies on the POFDs in the PubMed, Web of Science, Embase, and MEDLINE databases. The methodological quality of the studies was scored using the Methodological Index for Non-Randomized Studies (MINORS). A total of 117 patients were identified in the nine studies selected. The high-energy injuries accounted for 42.7% of the included studies. The rates of concomitant coronoid process, radial head fractures, and lateral collateral ligament injury were 84.6% (99/117), 87.2% (102/117), and 5% (6/117), respectively. The procedure was performed with a dorsal mid longitudinal approach to reconstruct all injury components. The postoperative clinical scores included the Broberg/Morrey rating, with a mean rating of excellent or good at 66%, the mean DASH score was 20.6, and the mean ASES score was 83. The flexion and extension arc and forearm rotation arcs were 100° and 134°, respectively. Complications included arthrosis in 28.2% (33/117) of cases, fracture nonunion or delayed union in 9.4% (11/117) of cases, heterotopic ossification in 7% (8/117) of cases, and the re-operation rate was 16% (19/117). There was nearly no postoperative ulnohumeral instability. The main characteristics of POFDs were disruptions of the trochlear notch, including the olecranon and coronoid processes, and severe radial head fractures, while the lateral collateral ligament was spared. Although the POFDs had a low frequency of instability, the prognosis was relatively poor. The POFDs should be considered independently.

Finite element study of the biomechanical effects on the rotator cuff under load.

Rotator cuff injuries account for 50% of shoulder disorders that can cause shoulder pain and reduced mobility. The occurrence of rotator cuff injury is related to the variation in shoulder load, but the mechanical changes in the rotator cuff caused by load remain unclear. Therefore, the mechanical results of the rotator cuff tissue during glenohumeral abduction and adduction were analyzed based on a finite element shoulder model under non-load (0 kg) and load (7.5 kg) conditions. The results showed that the maximum von Mises stress on the supraspinatus muscle was larger than that on the subscapularis, infraspinatus, and teres minor muscles during glenohumeral abduction. Compared with the non-load condition, the maximum von Mises stress on the supraspinatus muscle increased by 75% under the load condition at 30° abduction. Under the load condition, the supraspinatus joint side exhibited an average stress that was 32% greater than that observed on the bursal side. The von Mises stress on the infraspinatus muscle was higher than that in other rotator cuff tissues during adduction. The stress on the infraspinatus muscle increased by 36% in the load condition compared to the non-load condition at 30° adduction. In summary, the increased load changed the mechanical distribution of rotator cuff tissue and increased the stress differential between the joint aspect and the bursal aspect of the supraspinatus tendon.

Optimal treatment of ceftazidime-avibactam and aztreonam-avibactam against bloodstream infections or lower respiratory tract infections caused by extensively drug-resistant or pan drug-resistant (XDR/PDR) Pseudomonas aeruginosa.

Objective: To evaluate the efficacy of ceftazidime-avibactam (CZA) and aztreonam-avibactam (AZA) against bloodstream infections (BSIs) or lower respiratory tract infections (LRTIs) - caused by extensive drug-resistant or pan drug-resistant (XDR/PDR) Pseudomonas aeruginosa. Method: The two-fold dilution method was used to determine the minimum inhibitory concentrations (MICs) of CZA/AZA against XDR/PDR P. aeruginosa. Whole-genome sequencing was used to analyze the resistance determinants of each isolate. Monte Carlo simulations (MCSs) were used to evaluate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of each CZA/AZA dosing regimen via traditional infusion (TI)/optimized two-step-administration therapy (OTAT). Results: We found that XDR/PDR P. aeruginosa may carry some rare MBLs (e.g.: IND-6, SLB-1, THIN-B). P. aeruginosa isolates producing IMP-45, VIM-1, or VIM-2 were inhibited by AZA at a concentration of 2 to 8 mg/L. All isolates producing IND-6 plus other serine ß-lactamases were high-level resistant to CZA/AZA (MICs >64 mg/L). All simulated dosing regimens of CZA/AZA against BSIs-causing XDR/PDR P. aeruginosa achieved 100% PTA when the MIC was ≤32 mg/L. Conclusion: AZA has been considered as an option for the treatment of infections caused by XDR/PDR P. aeruginosa producing IMP-45, VIM-1, or VIM-2. OTAT with sufficient pharmacodynamic exposure may be an optimal treatment option for XDR/PDR P. aeruginosa with a high-level MIC of CZA/AZA.

Effect of different loads on the shoulder in abduction postures: a finite element analysis.

Load can change the mechanical environment of dynamic and static stable structures of the shoulder joint, increase the risk of tissue damage and affect the stability of the shoulder joint, but its biomechanical mechanism is still unclear. Therefore, a finite element model of the shoulder joint was constructed to analyze the mechanical index changes of shoulder joint abduction under different loads. The stress of the articular side on the supraspinatus tendon was higher than that of the capsular side, with a maximum difference of 43% due to the increased load. For the deltoid muscle and glenohumeral ligaments, increases in stress and strain were obvious in the middle and posterior deltoid muscles and inferior glenohumeral ligaments. The above results indicate that load increases the stress difference between the articular side and the capsular side on the supraspinatus tendon and increases the mechanical indices of the middle and posterior deltoid muscles, as well as the inferior glenohumeral ligament. The increased stress and strain in these specific sites can lead to tissue injury and affect the stability of the shoulder joint.

Fatty acid metabolites of Dendrobium nobile were positively correlated with representative endophytic fungi at altitude.

Introduction: Altitude, as a comprehensive ecological factor, regulates the growth and development of plants and microbial distribution. Dendrobium nobile (D. nobile) planted in habitats at different elevations in Chishui city, also shows metabolic differences and endophytes diversity. What is the triangular relationship between altitude, endophytes, and metabolites? Methods: In this study, the diversity and species of endophytic fungi were tested by ITS sequencing and metabolic differences in plants were tested by UPLC-ESI-MS/MS. Elevation regulated the colonization of plant endophytic fungal species and fatty acid metabolites in D. nobile. Results: The results indicate that and high altitude was better for the accumulation of fatty acid metabolites. Therefore, the high-altitude characteristic endophytic floras were screened, and the correlation with fatty acid metabolites of plants was built. The colonization of T. rubrigenum, P. Incertae sedis unclassified, Phoma. cf. nebulosa JZG 2008 and Basidiomycota unclassified showed a significantly positive correlation with fatty acid metabolites, especially 18-carbon-chain fatty acids, such as (6Z,9Z,12Z)-octadeca-6,9,12-trienoic acid, 3,7,11,15-tetramethyl-12-oxohexadeca-2,4-dienoic acid and Octadec-9-en-12-ynoic acid. What is more fascinating is these fatty acids are the essential substrates of plant hormones. Discussion: Consequently, it was speculated that the D. nobile- colonizing endophytic fungi stimulated or upregulated the synthesis of fatty acid metabolites and even some plant hormones, thus affecting the metabolism and development of D. nobile.

Ultrasonic irradiation enhanced the efficacy of antimicrobial photodynamic therapy against methicillin-resistant Staphylococcus aureus biofilm.

Antimicrobial photodynamic therapy (aPDT) is a non-pharmacological antimicrobial regimen based on light, photosensitizer and oxygen. It has become a potential method to inactivate multidrug-resistant bacteria. However, limited by the delivery of photosensitizer (PS) in biofilm, eradicating biofilm-associated infections by aPDT remains challenging. This study aimed to explore the feasibility of combining ultrasonic irradiation with aPDT to enhance the efficacy of aPDT against methicillin-resistant staphylococcus aureus (MRSA) biofilm. A cationic benzylidene cyclopentanone photosensitizer with much higher selectivity to bacterial cells than mammalian cells were applied at the concentration of 10 µM. 532 nm laser (40 mW/cm2, 10 min) and 1 MHz ultrasound (500 mW/cm2, 10 min, simultaneously with aPDT) were employed against MRSA biofilms in vitro. In addition to combined with ultrasonic irradiation and aPDT, MRSA biofilms were treated with laser irradiation only, photosensitizer only, ultrasonic irradiation only, ultrasonic irradiation and photosensitizer, and aPDT respectively. The antibacterial efficacy was determined by XTT assay, and the penetration depth of PS in biofilm was observed using a photoluminescence spectrometer and a confocal laser scanning microscopy (CLSM). In addition, the viability of human dermal fibroblasts (WS-1 cells) after the same treatments mentioned above and the uptake of P3 by WS-1 cells after ultrasonic irradiation were detected by CCK-8 and CLSM in vitro. Results showed that the percent decrease in metabolic activity resulting from the US + aPDT group (75.76%) was higher than the sum of the aPDT group (44.14%) and the US group (9.88%), suggesting synergistic effects. Meanwhile, the diffusion of PS in the biofilm of MRSA was significantly increased by 1 MHz ultrasonic irradiation. Ultrasonic irradiation neither induced the PS uptake by WS-1 cells nor reduced the viability of WS-1 cells. These results suggested that 1 MHz ultrasonic irradiation significantly enhanced the efficacy of aPDT against MRSA biofilm by increasing the penetration depth of PS. In addition, the antibacterial efficacy of aPDT can be enhanced by ultrasonic irradiation, the US + aPDT treatment demonstrated encouraging in vivo antibacterial efficacy (1.73 log10 CFU/mL reduction). In conclusion, the combination of aPDT and 1 MHz ultrasound is a potential and promising strategy to eradicate biofilm-associated infections of MRSA.