The immunosuppressive landscape in tumor microenvironment.

Recent advances in cancer immunotherapy, especially immune checkpoint inhibitors (ICIs), have revolutionized the clinical outcome of many cancer patients. Despite the fact that impressive progress has been made in recent decades, the response rate remains unsatisfactory, and many patients do not benefit from ICIs. Herein, we summarized advanced studies and the latest insights on immune inhibitory factors in the tumor microenvironment. Our in-depth discussion and updated landscape of tumor immunosuppressive microenvironment may provide new strategies for reversing tumor immune evasion, enhancing the efficacy of ICIs therapy, and ultimately achieving a better clinical outcome.

Optically pumped flexible GaN-based ultraviolet VCSELs.

Flexible optoelectronic platforms, which integrate optoelectronic devices on a flexible substrate, are promising in more complex working environments benefiting from the mechanical flexibility. Herein, for the first time to the best of our knowledge, a flexible GaN-based vertical cavity surface-emitting laser (VCSEL) in the ultraviolet A (UVA) range was demonstrated by using a thin-film transfer process based on laser lift-off (LLO) and spin-coating of a flexible substrate. The lasing wavelength is 376.5 nm with a linewidth of 0.6 nm and threshold energy of 98.4 nJ/pulse, corresponding to a threshold energy density of 13.9 mJ/cm2. The flexible substrate in this study is directly formed by spin-coating of photosensitive epoxy resin, which is much simplified and cost-effective, and a 2-in. wafer scale GaN-based membrane can be successfully transferred to a flexible substrate through this method. Such flexible UVA VCSELs are promising for the development of next-generation flexible and wearable technologies.

Bacteria from nodules of Abrus mollis Hance: genetic diversity and screening of highly efficient growth-promoting strains.

Introduction: Abrus mollis Hance. (AM) is an important species used in southern Chinese medicine. It is mainly found in Guangdong and Guangxi provinces in China, and it is effective in the treatment of hepatitis. Endophytic bacteria are known to affect the growth and quality of medicinal plants. However, there are limited reports describing endophytic bacteria related to AM. Methods: In the present study, Illumina-based 16S rRNA gene sequencing was used to investigate the endophytic bacterial communities of root nodules of AM at five sampling sites in Guangxi. In addition, 179 strains of endophytic bacteria were isolated and categorized into 13 haplotypes based on recA sequence analysis. Results: The phylogeny of the 16S rRNA gene sequences revealed a predominance of nonrhizobial endophytes. Microbial diversity analysis showed that Proteobacteria was the dominant phylum in all samples, while Bradyrhizobium was the dominant genus in different samples. An efficient strain, Rhizobium tropici FM-19, was screened and obtained through greenhouse experiments. The AM plants inoculated with this strain showed the best growth performance and high nitrogen fixation and nodulation capacity. Notably, total phenols and total flavonoids, important active components in AM, increased by 30.9 and 42.7%, respectively, after inoculation with Rhizobium tropici FM-19. Discussion: This study provides insights into the complex microbial diversity of AM nodules and provides strain information for the efficient cultivation of AM.

Phase-Transition-Promoted Thermoelectric Textiles Based on Twin Surface-Modified CNT Fibers.

With the fast development of new science and technology, wearable devices are in great demand in modern human daily life. However, the energy problem is a long-lasting issue to achieve real smart, wearable, and portable devices. Flexible thermoelectric generators (TEGs) based on thermoelectric conversion systems can convert body waste heat into electricity with excellent flexibility and wearability, which shows a new direction to solving this issue. Here in this work, polyethylenimine (PEI) and gold nanoparticles (Au NPs) twin surface-modified carbon nanotube fibers (CNTFs) were designed and prepared to fabricate thermoelectric textiles (TET) with high performance, good air stability, and high-efficiency power generation. To better utilize the heat emitted by the human body, microencapsulated phase change materials (MPCM) were coated on the hot end of the TET to achieve the phase-transition-promoted TET. MPCM-coated TET device could generate 25.7% more energy than the untreated control device, which indicates the great potential of the phase-transition-promoted TET.

Trading strategies of energy storage participation in day-ahead joint market based on Stackelberg game.

The goal of "carbon peak, carbon neutral" and the increasing expansion of new energy have helped to advance the development of energy storage. However, since the operating cost of energy storage is high, carbon emission trading and power market trading have emerged, effectively improving the efficiency. In this paper, a trading strategy and bidding framework of energy storage participation in the day-ahead joint market are studied. A market bidding model has been established in a framework based on the Stackelberg game. Finally, the "Day-Ahead and Intra-Day and Carbon Emission Trading (CET)" market clearing model has been constructed. It has been simplified to solve the equivalent mixed-integer linear programming (MILP) problem with equilibrium constraints through the use of the Karush-Kuhn-Tucker (KKT) optimality criterion and duality principle. The proposed model is validated through improved examples to obtain thermal unit output cuts of up to 32.2% during load trough periods, and up to 16.75% increase in clearing prices during peak load periods. The storage life is extended and the storage output variation is minimized.

Cyanobacterial blooms control with CaO2 in different stages: Inhibition efficiency, water quality optimization and microbial community changes.

This study explored the feasibility of calcium peroxide (CaO2) to inhibit cyanobacterial blooms of the outbreak and dormancy stages. Our previous studies have found that CaO2 has a high inhibitory effect on cyanobacteria. In order to explore the application effect of CaO2 in actual cyanobacteria lake water, we conducted this study to clarify the effect of CaO2 on inhibiting cyanobacteria in outbreak and dormancy stages. The results showed that CaO2 inhibited the growth of cyanobacteria in the outbreak and dormancy stages by 98.7% and 97.6%, respectively. The main inhibitory mechanism is: (1) destroy the cell structure and make the cells undergo programmed cell death by stimulating the oxidation balance of cyanobacteria cells; (2) EPS released by cyanobacteria resist stimulation and combine calcium to form colonies, and accelerate cell settlement. In addition to causing direct damage to cyanobacteria, CaO2 can also improve water quality and sediment microbial diversity, and reduce the release of sediment to phosphorus, so as to further contribute to cyanobacterial inhibition. Finally, the results of qRT-PCR analysis confirmed the promoting effect of CaO2 on the downregulation of photosynthesis-related genes (rbcL and psaB), microcystn (mcyA and mcyD) and peroxiredoxin (prx), and verified the mechanism of CaO2 inhibition of cyanobacteria. In conclusion, this study provides new findings for the future suppression of cyanobacterial bloom, by combining water quality, cyanobacterial inhibition mechanisms, and sediment microbial diversity.

PbrWRKY62-PbrADC1 module involves in superficial scald development of Pyrus bretschneideri Rehd.fruit via regulating putrescine biosynthesis.

Putrescine plays a role in superficial scald development during the cold storage of pear fruit. However, the molecular mechanism behind this phenomenon has not been un-fully clarified until recently. In this study, a conjoint analysis of metabolites and gene expression profiles in the putrescine-metabolic pathway of P. bretschneideri Rehd. fruit followed by experimental validation revealed that PbrADC1, forming a homodimer in the chloroplast, was involved in putrescine biosynthesis and thus fruit chilling resistance. Additionally, the substrate-binding residue Cys546 in PbrADC1, whose activity was modified by H2O2, played a crucial role in arginine decarboxylation into agmatine. Through a combined analysis of the distribution of cis-acting elements in the PbrADC1 promoter as well as the expression profiles of related transcription factors (TFs), several TFs were identified as upstream regulators of PbrADC1 gene. Further investigation revealed that the nuclear PbrWRKY62 could directly bind to the W-box elements in the PbrADC1 promoter, activate its expression, enhance putrescine accumulation, and thus increase fruit chilling tolerance. In conclusion, our results suggest that the PbrWRKY62-PbrADC1 module is involved in the development of superficial scald in P. bretschneideri Rehd. fruit via regulating putrescine biosynthesis. Consequently, these findings could serve as valuable genetic resources for breeding scald-resistant pear fruit.

Endosonography Elastography and Magnetic Resonance Imaging in the Restaging and Response Assessment of Rectal Cancer After Neoadjuvant Therapy.

ABSTRACT: The objective of this academic research is to assess the efficacy of conventional endorectal ultrasound (ERUS), ultrasonic shear wave elastography (SWE), and magnetic resonance imaging (MRI) techniques in evaluating the impact of neoadjuvant therapy (nCRT). Forty-five patients with advanced low rectal cancer (T ≥ 3) were included. Before and after nCRT, ERUS, SWE, and MRI evaluations were conducted. The T staging of ultrasound (uT) and MRI (mT) were evaluated and compared with the pathological T staging (ypT). The accuracy of the 2 diagnostic methods for T staging, and T downstaging was evaluated. The ultrasound elasticity difference and relative elasticity before and after treatment and pathological T downstaging were compared, and its cutoff value and the area under the curve were assessed. In terms of T staging accuracy after chemoradiotherapy, the values for ERUS, ERUS combined with SWE, and MRI were 64.4%, 71.1%, and 62.2%, respectively. No significant difference was observed among these groups ( P > 0.05). The accuracy of uT downstaging was 84.4%, and that of mT downstaging was 88.9%. The receiver operating characteristic curve of uLD and elastic differences and relative elasticity of T downstaging after treatment were 0.754, 0.817, and 0.886, respectively (all P < 0.05). Both ERUS and MRI can evaluate ypT downstaging. The indicators for evaluating T downstaging are uLD, elasticity difference, and relative elasticity, providing more reference for clinical assessment of nCRT efficacy.

Optimization strategy of power purchase and sale for electricity retailers in a two-tier market.

Against the backdrop of the gradual advancement of China's electricity market reform, the number of Power Trading Companies in China has been increasing year by year, and as of October 2022, the number has reached more than 10,000. As an important hub connecting the electricity market and users, electricity retailers face double risks from downstream user load fluctuations and electricity market price fluctuations. Therefore, a reasonable power purchase and sale strategy is very important for an electricity retailer. In this study, a block bidding mechanism is adopted to optimize the clearing of the medium-to long-term market and a DA-RBF neural network is established for spot electricity price forecasting model based on numerical feature similarity to improve the accuracy of electricity price forecasting. Furthermore, the model considers the differences in user demand responses and investigates the optimal power purchase and sale strategy, guided by differentiated time-of-use electricity pricing. The case study analysis demonstrated that the proposed power purchase and sale optimization strategy yields favorable results, improving profitability and enhancing the stability of the power system.

Soft tissue infection and osteomyelitis caused by Mycobacterium farcinogenes after heart surgery: Case report and literature review of human cases.

Mycobacterium farcinogenes (M. farcinogenes) is rapidly growing mycobacterium, belonging to non-tuberculous mycobacterial (NTM). M. farcinogenes is an exceedingly rare causative agent of human infection. Only seven cases with M. farcinogenes infections in humans were reported. This is a case of soft tissue infection and osteomyelitis caused by M. farcinogenes after heart surgery. Microbial identification was achieved by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The clinical outcome was favorable after surgical debridement and 4-month antibiotics treatment. We also provide a comprehensive literature review on this disease.

Corylifol A suppresses osteoclastogenesis and alleviates ovariectomy-induced bone loss via attenuating ROS production and impairing mitochondrial function.

Osteoporosis is a systemic disease characterized by an imbalance in bone homeostasis, where osteoblasts fail to fully compensate for the bone resorption induced by osteoclasts. Corylifol A, a flavonoid extracted from Fructus psoraleae, has been identified as a potential treatment for this condition. Predictions from network pharmacology and molecular docking studies suggest that Corylifol A exhibits strong binding affinity with NFATc1, Nrf2, PI3K, and AKT1. Empirical evidence from in vivo experiments indicates that Corylifol A significantly mitigates systemic bone loss induced by ovariectomy by suppressing both the generation and activation of osteoclasts. In vitro studies further showed that Corylifol A inhibited the activation of PI3K-AKT and MAPK pathways and calcium channels induced by RANKL in a time gradient manner, and specifically inhibited the phosphorylation of PI3K, AKT, GSK3 ß, ERK, CaMKII, CaMKIV, and Calmodulin. It also diminishes ROS production through Nrf2 activation, leading to a decrease in the expression of key regulators such as NFATcl, C-Fos, Acp5, Mmp9, and CTSK that are involved in osteoclastogenesis. Notably, our RNA-seq analysis suggests that Corylifol A primarily impacts mitochondrial energy metabolism by suppressing oxidative phosphorylation. Collectively, these findings demonstrate that Corylifol A is a novel inhibitor of osteoclastogenesis, offering potential therapeutic applications for diseases associated with excessive bone resorption.

An engineered Escherichia coli Nissle strain prevents lethal liver injury in a mouse model of tyrosinemia type 1.

BACKGROUND & AIMS: Hereditary tyrosinemia type 1 (HT1) results from the loss of fumarylacetoacetate hydrolase (FAH) activity and can lead to lethal liver injury. Therapeutic options for HT1 remain limited. In this study, we aimed to construct an engineered bacterium capable of reprogramming host metabolism and thereby provide a potential alternative approach for the treatment of HT1. METHODS: Escherichia coli Nissle 1917 (EcN) was engineered to express genes involved in tyrosine metabolism in the anoxic conditions that are characteristic of the intestine (EcN-HT). Bodyweight, survival rate, plasma (tyrosine/liver function), H&E staining and RNA sequencing were used to assess its ability to degrade tyrosine and protect against lethal liver injury in Fah-knockout (KO) mice, a well-accepted model of HT1. RESULTS: EcN-HT consumed tyrosine and produced L-DOPA (levodopa) in an in vitro system. Importantly, in Fah-KO mice, the oral administration of EcN-HT enhanced tyrosine degradation, reduced the accumulation of toxic metabolites, and protected against lethal liver injury. RNA sequencing analysis revealed that EcN-HT rescued the global gene expression pattern in the livers of Fah-KO mice, particularly of genes involved in metabolic signaling and liver homeostasis. Moreover, EcN-HT treatment was found to be safe and well-tolerated in the mouse intestine. CONCLUSIONS: This is the first report of an engineered live bacterium that can degrade tyrosine and alleviate lethal liver injury in mice with HT1. EcN-HT represents a novel engineered probiotic with the potential to treat this condition. IMPACT AND IMPLICATIONS: Patients with hereditary tyrosinemia type 1 (HT1) are characterized by an inability to metabolize tyrosine normally and suffer from liver failure, renal dysfunction, neurological impairments, and cancer. Given the overlap and complementarity between the host and microbial metabolic pathways, the gut microbiome provides a potential chance to regulate host metabolism through degradation of tyrosine and reduction of byproducts that might be toxic. Herein, we demonstrated that an engineered live bacterium, EcN-HT, could enhance tyrosine breakdown, reduce the accumulation of toxic tyrosine byproducts, and protect against lethal liver injury in Fah-knockout mice. These findings suggested that engineered live biotherapeutics that can degrade tyrosine in the gut may represent a viable and safe strategy for the prevention of lethal liver injury in HT1 as well as the mitigation of its associated pathologies.

Lessons learned from characteristics of extraordinarily severe traffic crashes in China, 2004-2019.

China has experienced remarkable achievements in terms of reducing the number of extraordinarily severe traffic crashes (ESTCs) that cause more than 10 deaths each crash. However, ESTCs still occur occasionally and result in extremely adverse social impacts. This study aims at investigating the common characteristics, characteristic patterns, and changes of characteristics of ESTCs in China with the expectation to learn from the past and act for the future. A total of 373 ESTCs occurred in 2004-2019 were collected, and characteristics of driver factors, road factors, vehicle factors, environment factors, and other factors were analyzed through the multiple correspondence analysis (MCA). The results show that run off road crashes, not qualified drivers, improper driving, large bus, overload, class II highway, and straight road sections are the most common categories of characteristics. In addition, four underlying characteristic patterns are identified through the MCA. Significant changes in characteristics and characteristic patterns are also found, and these changes are the results of various law enforcement, safety policies, educational interventions, and engineering interventions. It is also inferred that the specific law enforcement targeting to certain category of characteristics is more effective than the corresponding safety campaigns or policies in terms of ESTC prevention.

Oral magnesium prevents acetaminophen-induced acute liver injury by modulating microbial metabolism.

Acetaminophen overuse is a common cause of acute liver failure (ALF). During ALF, toxins are metabolized by enzymes such as CYP2E1 and transformed into reactive species, leading to oxidative damage and liver failure. Here, we found that oral magnesium (Mg) alleviated acetaminophen-induced ALF through metabolic changes in gut microbiota that inhibit CYP2E1. The gut microbiota from Mg-supplemented humans prevented acetaminophen-induced ALF in mice. Mg exposure modulated Bifidobacterium metabolism and enriched indole-3-carboxylic acid (I3C) levels. Formate C-acetyltransferase (pflB) was identified as a key Bifidobacterium enzyme involved in I3C generation. Accordingly, a Bifidobacterium pflB knockout showed diminished I3C generation and reduced the beneficial effects of Mg. Conversely, treatment with I3C or an engineered bacteria overexpressing Bifidobacterium pflB protected against ALF. Mechanistically, I3C bound and inactivated CYP2E1, thus suppressing formation of harmful reactive intermediates and diminishing hepatocyte oxidative damage. These findings highlight how interactions between Mg and gut microbiota may help combat ALF.

Visual outcomes and prognostic factors of early pars plana vitrectomy for open globe injury.

OBJECTIVES: To identify the clinical features and outcomes of early vitrectomy in patients with open globe injury (OGI) and the prognostic factors for visual outcome. METHODS: This retrospective observational case series included 390 eyes in 389 patients diagnosed with OGI receiving vitrectomy within four days after injury. Preoperative parameters included the injury types, wound locations, consequent tissue damages, initial visual acuity (VA), and ocular trauma score. Postoperative outcome measures included surgical procedures, retinal (re)attachment, complications, and final VA. The logistic analysis evaluated the prognostic factors for visual outcome. RESULTS: Intraocular foreign bodies (59.2%) and penetrating injuries (28.7%) were the most common injury types. Among the 165 eyes with retinal detachment (RD), 121 (73.3%) had retinal reattachment during early primary vitrectomy, and 32 (19.4%) were repaired during a second or subsequent surgery. Thirteen eyes (3.3%) were enucleated. The final VA improved from the initial level in 207 eyes (55.2%), remained unchanged in 123 (32.8%), and decreased in 45 (12.0%). Multivariable regression revealed that the injury zone, initial VA, RD, and endophthalmitis were associated with poor visual outcomes (P < 0.05). CONCLUSIONS: Higher zone injury, low initial VA, RD, and endophthalmitis are predictors of poor visual outcome in eyes undergoing early vitrectomy for OGI.

Appraising the causal relationship between thyroid function and rheumatoid arthritis: a two-sample bidirectional Mendelian randomization study.

Background: Hypothyroidism and hyperthyroidism are observationally associated with rheumatoid arthritis (RA), but causality is unclear. To evaluate the causal relationship between thyroid function and RA, we conducted a two-Sample bidirectional Mendelian Randomization (MR) study. Methods: Single nucleotide polymorphisms associated with six phenotypes were selected from the FinnGen biobank database, The ThyroidOmics Consortium database, and the IEU Open GWAS database. For the forward MR analysis, we selected hypothyroidism (N=213,390), Graves' disease (GD) (N=199,034), other types of hyperthyroidism (N=190,799), free thyroxine (FT4, N=49,269), and thyroid-stimulating hormone (TSH, N=54,288) as the five related thyroid function phenotypes for exposure, with RA (N=58,284) as the outcome. Reverse MR analysis selected RA as the exposure and five phenotypes of thyroid function as the outcome. The Inverse variance weighting (IVW) method was used as the primary analysis method, supplemented by weighted median (WM) and MR-Egger methods. Cochran's Q test, MR-PRESSO, MR-Egger regression methods, and leave-one-out analysis were employed to assess sensitivity and pleiotropy. Results: Forward MR evidence indicates that genetic susceptibility to hypothyroidism is associated with an increased risk of RA (ORIvw=1.758, P=7.61×10-5). Reverse MR evidence suggests that genetic susceptibility to RA is associated with an increased risk of hypothyroidism (ORIvw=1.274, P=3.88×10-20), GD (ORIvw=1.269, P=8.15×10-05), and other types of hyperthyroidism (ORIvw=1.141, P=1.80×10-03). There is no evidence to support a forward or reverse causal relationship between genetic susceptibility to RA and FT4, TSH. Conclusion: Our results provide genetic evidence supporting bidirectional causal relationships between thyroid function and RA. These findings inform preventive strategies and interventions targeting RA and thyroid dysfunction.

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.

Genome-wide identification, comparative analysis and functional roles in flavonoid biosynthesis of cytochrome P450 superfamily in pear (Pyrus spp.).

BACKGROUND: The cytochrome P450 (CYP) superfamily is the largest enzyme metabolism family in plants identified to date, and it is involved in many biological processes, including secondary metabolite biosynthesis, hormone metabolism and stress resistance. However, the P450 gene superfamily has not been well studied in pear (Pyrus spp.). RESULTS: Here, the comprehensive identification and a comparative analysis of P450 superfamily members were conducted in cultivated and wild pear genomes. In total, 338, 299 and 419 P450 genes were identified in Chinese white pear, European pear and the wild pear, respectively. Based on the phylogenetic analyses, pear P450 genes were divided into ten clans, comprising 48 families. The motif and gene structure analyses further supported this classification. The expansion of the pear P450 gene family was attributed to whole-genome and single-gene duplication events. Several P450 gene clusters were detected, which have resulted from tandem and proximal duplications. Purifying selection was the major force imposed on the long-term evolution of P450 genes. Gene dosage balance, subfunctionalization and neofunctionalization jointly drove the retention and functional diversification of P450 gene pairs. Based on the association analysis between transcriptome expression profiles and flavonoid content during fruit development, three candidate genes were identified as being closely associated with the flavonoid biosynthesis, and the expression of one gene was further verified using qRT-PCR and its function was validated through transient transformation in pear fruit. CONCLUSIONS: The study results provide insights into the evolution and biological functions of P450 genes in pear.

Appraising causal risk and protective factors for rheumatoid arthritis.

Aims: Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies. Methods: PubMed, Web of Science, and Embase were searched for MR studies on influencing factors in relation to RA up to October 2022. Meta-analyses of MR studies assessing correlations between various potential pathogenic factors and RA were conducted. Random-effect and fixed-effect models were used to synthesize the odds ratios of various pathogenic factors and RA. The quality of the study was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology using Mendelian Randomization (STROBE-MR) guidelines. Results: A total of 517 potentially relevant articles were screened, 35 studies were included in the systematic review, and 19 studies were eligible to be included in the meta-analysis. Pooled estimates of 19 included studies (causality between 15 different risk factors and RA) revealed that obesity, smoking, coffee intake, lower education attainment, and Graves' disease (GD) were related to the increased risk of RA. In contrast, the causality contribution from serum mineral levels (calcium, iron, copper, zinc, magnesium, selenium), alcohol intake, and chronic periodontitis to RA is not significant. Conclusion: Obesity, smoking, education attainment, and GD have real causal effects on the occurrence and development of RA. These results may provide insights into the genetic susceptibility and potential biological pathways of RA.

The METS-IR is independently related to bone mineral density, FRAX score, and bone fracture among U.S. non-diabetic adults: a cross-sectional study based on NHANES.

AIM: The purpose of this study was to investigate the association between the metabolic score for insulin resistance (METS-IR) and bone mineral density (BMD) in American non-diabetic adults. METHODS: We conducted a cross-sectional study with 1114 non-diabetic adults from the National Health and Nutrition Examination Survey cycle (2013-2014). The associations between METS-IR and BMD of total femur and spine were assessed by the multiple linear regression and verified the non-linear relationship with a smooth curve fit and threshold effect model. Furthermore, we evaluated the relationship between METS-IR, FRAX score, and history of bone fractures. RESULTS: We found that BMD of the total femur and spine increased by 0.005 g/cm3 and 0.005 g/cm3, respectively, for a one-unit increase of METS-IR in all participants. This positive association was more pronounced among higher METS-IR participants, and there was a non-linear relationship, which was more significant when the MTTS-IRfemur was < 41.62 or the METS-IRspine was < 41.39 (ßfemur = 0.008, ßspine = 0.011, all P < 0.05). We also found that METS-IR was positively correlated with both FRAX scores in all female participants. However, METS-IR was positively correlated only with the 10-year hip fracture risk score in male participants with fractures. No significant association between METS-IR and a history of bone fractures. CONCLUSIONS: In American non-diabetic adults, there is a correlation between elevated levels of METS-IR within the lower range and increased BMD as well as decreased risk of fractures, suggesting that METS-IR holds promise as a novel biomarker for guiding osteoporosis (OP) prevention. However, it is important to carefully balance the potential benefits and risks of METS-IR in OP.