Aggregation-Induced Emissive Feringa-Type Motor: Toward the Dual-Functional Motor in a Single Molecular Aggregation System.

Aggregation-induced emission (AIE)allows tunable photoluminescence via the simple regulation of molecular aggregation. The research spurt along this vein has also offered tremendous opportunities for light-responsive artificial molecular machines that are to be fully explored for performing versatile functions. Herein, the study reports a light-driven Feringa-type motor, when in the appropriate aggregation state, not only demonstrates the light-activated rotary motion but emits photons with good quantum yield. A semi-quantitative TD-DFT calculation is also conducted to aid the understanding of the competitive photoluminescence and photoisomerization processes of the motor. Cytotoxicity test shows this motor possesses good biocompatibility, laying a solid foundation for applying it in the bio-environment. The results demonstrated that the engagement of the aggregation-induced emission concept and light-driven Feringa-motor can lead to the discovery of the novel motorized AIEgen, which will further stimulate the rise of more advanced molecular motors capable of executing multi-functionalities.

Long-term surface composts application enhances saline-alkali soil carbon sequestration and increases bacterial community stability and complexity.

Organic composts could remediate saline-alkali soils on agricultural land by amending soil micro-environment which is one of the main strategies for resourceful treatment and recycling of livestock manure. However, it was still unknown how long-term surface application of organic composts affects the microhabitat and bacterial community characteristics and assembly processes on the profile. We examined the features of the soil properties, bacterial community, and assembly models after 7-years composts application. Physicochemical indicators, enzyme activities, and bacterial diversity of the saline-alkali farmland were all enhanced by the surface composts application, particularly in the 0-20 cm. The network analysis showed that the surface application of composts significantly enhanced the robustness and topological characteristics of the bacterial community and that bacteria from Acidobacteriota were the keystone of the saline-alkali soils improvement. Composts also greatly increased the ecological niche of the bacterial community, while stochastic processes (mainly dispersal limitation) significantly shaped the bacterial community compared to the control. Structural equation modeling indicated that composts application promoted bacterial community succession, which in turn promoted elevated total organic carbon and improved saline-alkali soils properties. Overall, the study linked the ecological characteristics of soil microhabitats and bacterial communities during the restoration of saline-alkali soils by long-term surface application of composts, providing the management and remediation of saline-alkali agricultural soil with a theoretical foundation and technological support.

Endogenous electric field coupling Mxene sponge for diabetic wound management: haemostatic, antibacterial, and healing.

Improper management of diabetic wound effusion and disruption of the endogenous electric field can lead to passive healing of damaged tissue, affecting the process of tissue cascade repair. This study developed an extracellular matrix sponge scaffold (K1P6@Mxene) by incorporating Mxene into an acellular dermal stroma-hydroxypropyl chitosan interpenetrating network structure. This scaffold is designed to couple with the endogenous electric field and promote precise tissue remodelling in diabetic wounds. The fibrous structure of the sponge closely resembles that of a natural extracellular matrix, providing a conducive microenvironment for cells to adhere grow, and exchange oxygen. Additionally, the inclusion of Mxene enhances antibacterial activity(98.89%) and electrical conductivity within the scaffold. Simultaneously, K1P6@Mxene exhibits excellent water absorption (39 times) and porosity (91%). It actively interacts with the endogenous electric field to guide cell migration and growth on the wound surface upon absorbing wound exudate. In in vivo experiments, the K1P6@Mxene sponge reduced the inflammatory response in diabetic wounds, increased collagen deposition and arrangement, promoted microvascular regeneration, Facilitate expedited re-epithelialization of wounds, minimize scar formation, and accelerate the healing process of diabetic wounds by 7 days. Therefore, this extracellular matrix sponge scaffold, combined with an endogenous electric field, presents an appealing approach for the comprehensive repair of diabetic wounds.

Role of keystone drives polycyclic aromatic hydrocarbons degradation and humification especially combined with aged contaminated soil in co-composting.

Accumulation of persistent organic pollutants polycyclic aromatic hydrocarbons (PAHs) in soil has become a global problem. Composting is considered one of the more economical methods of soil remediation and is important for the resourceful use of wastes. Agroforestry waste is produced in huge amounts and is utilized at low rates, hence there is an urgent need to manage it. Here, leaf (LVS) or rice straw (SVS) was co-composting with aged contaminated soil to investigate bacteria interaction to PAHs degradation and humus formation. The degradation rate of high molecular weight PAHs (HMW-PAHs) in LVS and SVS reached 58.9% and 52.5%, and the low molecular weight PAHs (LMW-PAHs) were 77.5% and 65%. Meanwhile, the humus increased by 44.8% and 60.5% in LVS and SVS at the end of co-composting. The topological characteristics and community assembly of the bacterial community showed that LVS had higher complexity and more keystones than SVS, suggesting that LVS might more beneficial for the degradation of PAHs. The stability of the co-occurrence network and stochastic processes (dispersal limitation) dominated community assembly made SVS beneficial for humus formation. Mantel test and structural equation models indicated that the transformation of organic matter was important for PAHs degradation and humus formation. Degradation of HMW-PAHs led to bacterial succession, which affected the formation of precursors and ultimately increased the humus content. This study provided potential technology support for improving the quality of agroforestry organic waste composting and degrading PAHs in aged contaminated soil.

Self-Assembly of an Anionic [Cu5I8]3- Supramolecular Cluster Driven by Ion-Pair Interaction and Catalytic Properties.

The rational design and controlling synthesis of an anionic cuprous iodide supramolecular cluster with high nuclearity through noncovalent interactions remains a significant challenge. Herein, a cationic organic ligand (L1)3+ was driven by anion-cation ion-pair electrostatic interaction to induce free cuprous iodide to aggregate into an anionic supramolecular cluster, [(Cu5I8)3-(L1)3+] (C1). Moreover, five copper(I) atoms bind with eight iodides through multiply bridged Cu-I bonds associated with intramolecular cuprophilic interactions in this butterfly-shaped cluster core. Supramolecular cluster C1 exhibited a solid-state emission at 380 nm and an emission at 405 nm in acetonitrile at room temperature, respectively. Interestingly, this unprecedented cuprous iodide cluster demonstrated a good catalytic performance for azide-alkyne cycloaddition reaction (CuAAC) and the catalytic yield can be up to 80% for eight different substrates at 80 °C. Furthermore, the density functional theory (DFT) calculation revealed that the thermodynamic-dependent cycloaddition reaction underwent a four-step pathway with an overall energy barrier of -43.6 kcal mol-1 on the basis of intermediates monitored by mass spectrum.

Efficacy and Postoperative Complication Rates of Different Surgical Approaches for Calcaneal Fractures: A Network Meta-analysis.

Context: Calcaneal fractures (CFs) are the most common kind of tarsal fracture. The choice of surgical approach is a key element in the management of CFs, but the best method remains in dispute. Also, no single approach is appropriate for all kinds of CFs. Objective: The study intended to evaluate the relationship between six surgical approaches for clinical treatment of CFs and prevention of postoperative complications, to provide an evidence-based approach for treatment. Design: The research team performed a meta-analysis using the data from a previously published review and updating that data through a new narrative review. The team performed a systematic search in PubMed, Embase, the Cochrane Library, and the Chinese National Knowledge Internet (CNKI) from inception until January 2022, with no language restrictions. The search used the following keywords for the search: calcaneus, heel bone, surgical wounds, surgical incisions, prospective trials, prospective trials, and randomized controlled trials. Outcome Measures: The research team compared the complication rates, American Orthopedic Foot and Ankle Society (AOFAS) scores, and Bohler's angles for the six surgical approaches, which were: (1) the extensive lateral approach (ELA), (2) the sinus tarsi approach (STA), (3) the horizontal arc approach (HAA), (4) the longitudinal approach (LA), (5) the oblique lateral incision (OLI), and (6) the modified incision (MI)). The team summarized the results using a random effects model. Results: The research team analyzed the data from 19 RCTs with 1521 participants. They all were randomized controlled trials (RCTs). The complication rates were available for 18 studies, which included 1474 participants. The rates were significantly lower: (1) for HAA compared to ELA, [OR=-2.03; 95% CrI: [-3.63, -0.43)]; (2) for LA compared to ELA (OR=-1.83; 95% CrI: [-2.83, -0.84]); and (3) for STA compared to ELA (OR=- 1.22; 95% CrI: [-1.67, -0.78]). Of the 19 studies, 11 RCTs, with 942 participants, used the AOFAS scale. The probabilities for the surface under the cumulative ranking curve (SUCRA) indicated that OLI (0.694 ) >LA (0.596) >HAA (0.51) >STA (0.477) >ELA (0.224). In addition, ELA had the worst SUCRA (0.224). Of the 19 studies, 15 RCTs, with 1376 participants, used the Bohler angle as an outcome measure. The probability of SUCRA for the surgical approaches indicated that LA (0.723) >ELA (0.667) >STA (0.468) >HAA (0.373) >MI (0.27). Conclusions: The meta-analysis provides an evidence-based approach to the clinical treatment of CFs for six surgical approaches. HAA had the best outcomes, and ELA had the worst.

Exploration of bacterial community-induced polycyclic aromatic hydrocarbons degradation and humus formation during co-composting of cow manure waste combined with contaminated soil.

To solve polycyclic aromatic hydrocarbons (PAHs) pollution, composting was chosen as a remediation method. During composting, the dissipation of PAHs was carried out by resource utilization of organic solid waste and its degradation by bacteria. This study was conducted by co-composting with contaminated soil and cow manure. The results showed that the degradation rates of naphthalene (Nap), phenanthrene (Phe), and benzo[α]pyrene (BaP) could reach 82.2%, 79.4%, and 59.6% respectively during composting. Cluster analysis indicated that polyphenol oxidase (PPO), laccase, and protease were important drivers of PAHs transformation. The content of humic substances (HS) was 106.67 g/kg in PAH treatment, which was significantly higher than that in the control group at 65 days. The phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) and network analysis was used to infer the degradation mechanism of PAHs by microorganisms. The degradation of PAHs by PPO was found to have a significant contribution to the formation of HS. It was shown that PAHs and metabolic intermediates were more inclined to be oxidized and decomposed by PPO to form quinone, which in turn condensed with amino acids to form HS. Composting could promote the degradation of PAHs while improving the quality of compost, achieving a win-win situation.

Identify the potential driving mechanism of reconstructed bacterial community in reduce CO2 emissions and promote humus formation during cow manure composting.

The mineralization of organic components releases CO2 during composting, which not only leads to the loss of organic carbon, but has a direct negative impact on the environment. Malonic acid as a competitive inhibitor of succinate dehydrogenase could affect the tricarboxylic acid (TCA) cycle and reduce CO2 emissions. However, the bacterial interaction and organic component transformation has less known how to malonic acid reduce CO2 and improve of humus synthesis in complex composting. The aim of this study was to investigated the malonic acid on organic carbon sequestration and transforming cow manure waste into products with high humus content. Humus content was elevated by 16.8% and cumulative CO2 emissions (30 d)d reduced by 13.6% after malonic acid addition compared to the CK. SparCC analysis of bacterial interaction presented that the network complexity and stability was more higher with malonic acid addition, while a greater concentration of keystones and their ecological metabolic functions was observed, suggesting they weaken the influence of TCA cycle inhibition by enhancing interactions. PICRUSt predictions indicate that malonic acid might enhance humus content by promoting the synthesis of polyphenols and polymerization with amino acids. This study investigated the potential mechanism of regulators to enhance quality and reduce emissions during humification process, providing a new strategy for the resource utilization of organic solid waste.

MY11 exerts antitumor effects through activation of the NF-κB/PUMA signaling pathway in breast cancer.

Breast cancer is the most common malignancy in women worldwide, and the discovery of new effective breast cancer therapies with lower toxicity is still needed. We screened a series of chalcone derivatives and found that MY11 ((E)-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-(4-piperazinylphenyl) prop-2-en-1-one) had the strongest anti-breast cancer activity. MY11 inhibited the growth of MDA-MB-231 and MCF-7 breast cancer cells by arresting the cell cycle and promoting apoptosis, through regulation of the cell cycle and apoptosis-related proteins. PDTC (Pyrrolidinedithiocarbamate ammonium), a specific inhibitor of the NF-κB pathway, abolished the inhibitory effect of MY11 treatment. NF-κB has been shown to regulate PUMA-dependent apoptosis. Our in vitro studies demonstrated that MY11 promoted breast cancer cell apoptosis by activating the NF-κB/PUMA/mitochondrial apoptosis pathway (including Bcl-2, Bax, and Caspase-9). MY11 also inhibited tumor growth in an orthotopic breast cancer mouse model by inducing apoptosis through the NF-κB signaling pathway, importantly, with minimal toxicity. In addition, MY11 was found by docking analysis to bind to p65, which might enhance the stability of the p65 protein. Taken together, our findings indicate that MY11 exerts a significant anticancer effect in breast cancer and that it may be a potential candidate for the treatment of breast cancer.

Total flavonoids of Rhizoma drynariae promote angiogenesis and osteogenesis in bone defects.

Bone defects are difficult to heal, which conveys a heavy burden to patients' lives and their economy. The total flavonoids of Rhizoma drynariae (TFRD) can promote the osteogenesis of distraction osteogenesis. However, the dose effect is not clear, the treatment period is short, and the quality of bone formation is poor. In our study, we observed the long-term effects and dose effects of TFRD on bone defects, verified the main ingredients of TFRD in combination with network pharmacology for the first time, explored its potential mechanism, and verified these findings. We found that TFRD management for 12 weeks regulated osteogenesis and angiogenesis in rats with 4-mm tibial bone defects through the PI3K/AKT/HIF-1α/VEGF signaling pathway, especially at high doses (135 mg kg-1  d-1 ). The vascularization effect of TFRD in promoting human umbilical vein endothelial cells was inhibited by PI3K inhibitors. These results provide a reference for the clinical application of TFRD.

The antimicrobial protein REG3A regulates keratinocyte proliferation and differentiation after skin injury.

Epithelial keratinocyte proliferation is an essential element of wound repair, and abnormal epithelial proliferation is an intrinsic element in the skin disorder psoriasis. The factors that trigger epithelial proliferation in these inflammatory processes are incompletely understood. Here we have shown that regenerating islet-derived protein 3-alpha (REG3A) is highly expressed in keratinocytes during psoriasis and wound repair and in imiquimod-induced psoriatic skin lesions. The expression of REG3A by keratinocytes is induced by interleukin-17 (IL-17) via activation of keratinocyte-encoded IL-17 receptor A (IL-17RA) and feeds back on keratinocytes to inhibit terminal differentiation and increase cell proliferation by binding to exostosin-like 3 (EXTL3) followed by activation of phosphatidylinositol 3 kinase (PI3K) and the kinase AKT. These findings reveal that REG3A, a secreted intestinal antimicrobial protein, can promote skin keratinocyte proliferation and can be induced by IL-17. This observation suggests that REG3A may mediate the epidermal hyperproliferation observed in normal wound repair and in psoriasis.

A validated UPLC-MS/MS method for quantitative determination of a potent neuroprotective agent Sarsasapogenin-AA13 in rat plasma: Application to pharmacokinetic studies.

Sarsasapogenin-AA13(AA13), a sarsasapogenin derivative, exhibited good neuroprotective and anti-inflammatory activities in vitro and therapeutic effects on learning and memory dysfunction in amyloid-ß-injected mice. A sensitive UPLC-MS/MS method was developed and validated to quantitatively determine AA13 in rat plasma and was further applied to evaluate the pharmacokinetic behaviour of AA13 in rats that were administered AA13 intravenously and orally. This method was validated to exhibit excellent linearity in the concentration range of 1-1000 ng/mL. The lower limit of quantification was 1 ng/mL for AA13 in rat plasma. Intra-day accuracy for AA13 was in the range of 90-114%, and inter-day accuracy was in the range of 97-103 %. The relative standard deviation of intra-day and inter-day assay was less than 15%. After a single oral administration of AA13 at the dose of 25 mg/kg, Cmax of AA13 was 1266.4 ± 316.1 ng/mL. AUC0-48 h was 6928.5 ± 1990.1 h·ng/mL, and t1/2 was 10.2 ± 0.8 h. Under intravenous administration of AA13 at a dosage of 250 µg/kg, AUC0-48 h was 785.7 ± 103.3 h⋅ng/mL, and t1/2 was 20.8 ± 7.2 h. Based on the results, oral bioavailability (F %) of AA13 in rats at 25 mg/kg was 8.82 %.

Development and validation of a UPLC-MS/MS method for determination of Sarsasapogenin-AA22 in rat plasma and its application to a pharmacokinetic study.

A sarsasapogenin derivative, sarsasapogenin-AA22 (AA22), with cyclobutylamine at the 3-hydroxyl position of sarsasapogenin, has great neuroprotective activity in PC12 cells and NO production inhibitory activity in RAW264.7 cell lines. A method was developed to determine AA22 in rat plasma which was further applied to evaluate the pharmacokinetics of AA22 after taking a single dose of AA22. Liquid chromatography tandem mass spectrometry was used in the method, while diosgenin was used as internal standard. A simple protein precipitation based on acetonitrile was utilized. A simple sample cleanup promoted the throughput of the method considerably. The method was validated over the range of 1-1000 ng/mL with a correlation coefficient > 0.99. The lower limit of quantification was 1 ng/mL for AA22 in plasma. Intra- and inter-day accuracies for AA22 were 92-111 and 100-103%, respectively, and the inter-day precision was <15%. After a single oral dose of 25 mg/kg of AA22, the mean peak plasma concentration of AA22 was 2114 ± 362 ng/mL at 6 h. The area under the plasma concentration-time curve was 196,098 ± 69,375 h ng/mL, and the elimination half-life was 8.7 ± 2.2 h.

Interleukin-33 increases antibacterial defense by activation of inducible nitric oxide synthase in skin.

Interleukin-33 (IL-33) is associated with multiple diseases, including asthma, rheumatoid arthritis, tissue injuries and infections. Although IL-33 has been indicated to be involved in Staphylococcus aureus (S. aureus) wound infection, little is known about how IL-33 is regulated as a mechanism to increase host defense against skin bacterial infections. To explore the underlying intricate mechanism we first evaluated the expression of IL-33 in skin from S. aureus-infected human patients. Compared to normal controls, IL-33 was abundantly increased in skin of S. aureus-infected patients. We next developed a S. aureus cutaneous infection mouse model and found that IL-33 was significantly increased in dermal macrophages of infected mouse skin. The expression of IL-33 by macrophages was induced by staphylococcal peptidoglycan (PGN) and lipoteichoic acid (LTA) via activation of toll-like receptor 2(TLR2)-mitogen-activated protein kinase (MAPK)-AKT-signal transducer and activator of transcription 3(STAT3) signaling pathway as PGN and LTA failed to induce IL-33 in Tlr2-deficient peritoneal macrophages, and MAPK,AKT, STAT3 inhibitors significantly decreased PGN- or LTA-induced IL-33. IL-33, in turn, acted on macrophages to induce microbicidal nitric oxygen (NO) release. This induction was dependent on inducible nitric oxide synthase (iNOS) activation, as treatment of macrophages with an inhibitor of iNOS, aminoguanidine, significantly decreased IL-33-induced NO release. Moreover, aminoguanidine significantly blocked the capacity of IL-33 to inhibit the growth of S. aureus, and IL-33 silencing in macrophages significantly increased the survival of S. aureus in macrophages. Furthermore, the administration of IL-33-neutralizing antibody into mouse skin decreased iNOS production but increased the survival of S. aureus in skin. These findings reveal that IL-33 can promote antimicrobial capacity of dermal macrophages, thus enhancing antimicrobial defense against skin bacterial infections.

Oral antibiotic treatment induces skin microbiota dysbiosis and influences wound healing.

Antibiotic treatment eliminates commensal bacteria and impairs mucosal innate immune defenses in the gut. However, whether oral antibiotic treatment could alter the composition of the microbiota on the skin surface and influence innate immune responses remains unclear. To test this, mice were treated with vancomycin for 7 days and then wounds were made on the back skin of the mice. Five days later, scar tissue from each mouse was collected for bacterial enumeration, the bacterial composition on the scar and unwounded skin was determined using 16S RNA gene-based pyrosequencing analysis, and skin around wounds was collected for RNA extraction. Compared with the control group, the overall density and composition of skin bacteria were altered, and the proportion of Staphylococcus-related sequences was reduced in the vancomycin-treated group. Moreover, vancomycin treatment decreased the expression of RegIIIγ and interleukin (IL)-17 in the wounded skin. Taken together, our data demonstrate that antibiotic treatment decreases the bacterial density and alters the bacterial composition in skin wounds, followed by a decrease in RegIIIγ expression, which may contribute to the delayed wound repair. Our findings also indicate that antibiotic therapy should be carefully considered in the treatment of skin injury.

Differentially expressed miR-4310 functions as a tumor suppressor in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a digestive tract malignancy microRNAs (miRNAs) have attracted much attention as biomarkers in tumor studies. OBJECTIVE: This work focused on the predictive potential and mechanism of miR-4310 in CRC. METHODS: The miRNA expression profile sets were obtained from the Gene Expression Omnibus (GEO) database, and the appropriate miRNA was screened by GEO2R. The CRC tissues and control tissues of 88 patients with CRC were collected, and the expression of miR-4310 was detected by quantitative real-time PCR, and the efficacy of miR-4310 in diagnosing CRC was evaluated by the receiver operating characteristic curve (ROC). The effects of miR-4310 on the proliferation, migration, and invasion of CRC cells were explored by Cell Counting Kit-8 (CCK-8) and Transwell experiments. Predicting the potential binding sites of miR-4310 and Runt-related transcription factor 1 (RUNX1) by four predictive websites. The relationship between miR-4310 and RUNX1 was confirmed by a double luciferase reporter gene experiment. RESULTS: The bioinformatics analysis found that miR-4310 was differentially expressed in CRC tissues and this finding was certified by the expression of miR-4310 in CRC tissues of collected patients and cultured CRC cell lines. The expression of miR-4310 had a predictive possibility for CRC patients. MiR-4310/RUNX1 pathway had effects on CRC viability, migration, and invasion. CONCLUSION: MiR-4310 had the potential to be a biomarker for early screening of CRC. MiR-4310 and RUNX1 participated in the regulation of CRC cells.

Prognostic and clinicopathological value of systemic immune-inflammation index in patients with osteosarcoma: a meta-analysis.

Background: The efficiency of systemic immune-inflammation index (SII) in predicting prognosis of osteosarcoma (OSA) patients has been extensively analyzed, but no consistent findings are obtained. Therefore, this meta-analysis focused on identifying the precise prognostic value of SII for OSA. Methods: We comprehensively searched electronic databases of PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI) from inception to 24 February, 2024. Meanwhile, the efficiency of SII in predicting prognosis of OSA was evaluated by calculating pooled hazard ratios (HRs) as well as 95% confidence intervals (CIs). Additionally, the correlation of SII with the OSA clinicopathological characteristics was analyzed based on pooled odds ratios (ORs) and 95%CIs. Results: Six studies with 1015 cases were enrolled into this work. According to the combined data, the higher SII was markedly related to poor overall survival (OS) (HR=2.01, 95%CI=1.30-3.09, p=0.002) and Enneking stage III (OR=2.21, 95%CI=1.11-4.39, p=0.024) of patients with OSA. Nonetheless, SII was not significantly related to gender, age, pathological fracture, tumor size, tumor location, tumor differentiation, and metastasis in patients with OSA. Conclusions: In summary, the higher SII is markedly related to poor OS and advanced Enneking stage in OSA patients. Systematic review registration: https://inplasy.com/inplasy-2024-7-0107/, identifier INPLASY202470107.

Comparisons of infection events associated with tumor necrosis factor inhibitors in patients with inflammatory arthritis: A systematic review and network meta-analysis.

Objective: To compare the risk of infection in inflammatory arthritis patients treated with tumor necrosis factor (TNF) inhibitors. Methods: PubMed, Embase, and the Cochrane Library were systematically searched from inception to 28 December 2023 for randomized controlled trials (RCTs) assessing TNF inhibitors and reporting infections. Subsequently, pairwise and network meta-analyses were conducted to determine odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Results: A total of 61 RCTs involving 20,458 patients were included. Pairwise meta-analysis revealed that certolizumab pegol was significantly associated with an increased risk of serious infection compared to placebo (OR:2.28, 95% CI: 1.13-4.62). Both adalimumab and certolizumab pegol were also significantly associated with an increased risk of any infection compared to placebo (OR:1.18, 95% CI: 1.06 to 1.30 and OR:1.40, 95% CI: 1.11 to 1.76, respectively). Moreover, a network meta-analysis indicated that certolizumab pegol and infliximab were associated with a higher risk of serious infection compared to other TNF inhibitors. In the cumulative ranking of any infection risk, certolizumab pegol had the highest risk compared with others. TNF inhibitors increased the risk of tuberculosis but not that of herpes zoster. Conclusion: Available evidence indicates etanercept and golimumab are likely associated with a lower risk of infection compared to other TNF inhibitors in inflammatory arthritis. For patients at a heightened risk of infection, prioritizing the use of etanercept and golimumab may be advisable to minimize patient risk. Systematic Review Registration: identifier CRD42022316577.

Tracing links between micronutrients and type 2 diabetes risk: the singular role of selenium.

Background: Type 2 diabetes (T2D) is a growing global health concern. While micronutrients are crucial for physiological functions and metabolic balance, their precise links to T2D are not fully understood. Methods: We investigated the causal relationships between 15 key micronutrients and T2D risk using both univariate and multivariate Mendelian randomization (MR) methods. Our analysis leveraged data from a large prospective cohort genome-wide association study (GWAS) on these micronutrients and T2D. We employed MR techniques such as inverse variance weighting (IVW), MR Egger, weighted median, and simple models. Multivariate analysis adjusted for diabetes-related factors like body mass index (BMI) and hypertension to assess the independent effects of micronutrients, particularly selenium, on T2D risk. Results: Selenium intake was associated with an increased risk of T2D, with an odds ratio (OR) of 1.045, a 95% confidence interval (CI) ranging from 1.009 to 1.082, and a P-value of 0.015. This association was consistent in multivariate analyses, suggesting an independent effect of selenium on T2D risk after adjusting for confounders. Conclusion: Our study presents novel evidence of a positive correlation between selenium intake and T2D risk, underscoring the importance of micronutrients in diabetes prevention and treatment strategies. Further research is necessary to confirm these findings and to clarify the specific biological mechanisms through which selenium influences diabetes risk.

Causal associations between human gut microbiota and osteomyelitis: a Mendelian randomization study.

Background: Recent studies have emphasized the role of gut microbiota in the onset and progression of osteomyelitis. However, the exact types of gut microbiota and their mechanisms of action remain unclear. Additionally, there is a lack of theoretical support for treatments that improve osteomyelitis by altering the gut microbiota. Methods: In our study, we utilized the largest genome-wide association study (GWAS) meta-analysis to date from the MiBioGen consortium, involving 13,400 participants. The GWAS data for osteomyelitis were sourced from the UK Biobank, which included 4,836 osteomyelitis cases and 486,484 controls. We employed a two-sample Mendelian randomization framework for a detailed investigation into the causal relationship between gut microbiota and osteomyelitis. Our methods included inverse variance weighting, MR-Egger, weighted median, and weighted mode approaches. Additionally, we applied Cochran's Q statistic to assess the heterogeneity of the instrumental variable. Results: At the class level, Bacilli and Bacteroidia were positively correlated with the risk of osteomyelitis. At the order level, only Bacteroidales showed a positive association with osteomyelitis. At the genus level, an increased abundance of Butyricimonas, Coprococcus3, and Tyzzerella3 was positively associated with the risk of osteomyelitis, whereas Lachnospira was negatively associated. Sensitivity analyses showed no evidence of heterogeneity or pleiotropy. Conclusion: This study reveals that classes Bacilli and Bacteroidia, order Bacteroidales, and genera Butyricimonas, Coprococcus3, and Tyzzerella3 are implicated in increasing the risk of osteomyelitis, while the genus Lachnospira is associated with a reduced risk. Future investigations are warranted to elucidate the precise mechanisms through which these specific bacterial groups influence the pathophysiology of osteomyelitis.