Hypothyroidism's effect on stroke limited to specific subtypes: A Mendelian randomization study.

BACKGROUND: The association between hypothyroidism and stroke remains controversial and the association between hypothyroidism and stroke subtypes has not been satisfactorily researched. This study aimed to explore the causal effect of hypothyroidism on the risk of stroke and its subtypes by Mendelian randomization (MR) analysis. METHODS: Single nucleotide polymorphisms (SNPs) were selected from published genome-wide association studies (GWAS) meta-analysis as instrumental variables (IVs) for hypothyroidism. As outcomes, summary GWAS data for stroke and its subtypes were obtained from two other large GWAS meta-analyses, including any stroke (AS), any ischemic stroke (AIS), large vessel stroke (LAS), cardiogenic embolic stroke (CES), small vessel stroke (SVS), and intracranial hemorrhage (ICH). Univariate Mendelian randomization (UVMR) and multivariate Mendelian randomization (MVMR) were used to assess the causal effect of hypothyroidism on stroke and its subtypes. RESULTS: In UVMR, genetically predicted hypothyroidism was significantly associated with LAS (OR = 1.14, 95CI = 1.02-1.27) and SVS (OR = 1.14, 95CI = 1.04-1.25), but not with AS, AIS, CES, and ICH. The results of the MVMR showed that after adjusting for smoking, alcohol consumption, hypertension, diabetes, low-density lipoprotein cholesterol (LDL-c), and body mass index (BMI), the causal association between hypothyroidism and SVS remained significant, while the association between hypothyroidism and LAS became nonsignificant. CONCLUSION: Hypothyroidism is causally associated with risk for LAS and SVS, but not for other stroke subtypes. Hypothyroidism may be an independent risk factor for SVS, and vascular risk factors play an important role in hypothyroidism causing LAS.

Causal association between plant foods intake and Alzheimer's disease: a Mendelian randomization study.

BACKGROUND: Alzheimer's disease (AD) is a degenerative disease of the nervous system. Observational studies have found an association between plant food intake and AD. However, it is unclear whether this association is influenced by confounding factors. We aimed to explore the causal relationship between plant-based diet and the risk of AD using two-sample Mendelian randomization. MATERIALS AND METHODS: We obtained datasets of exposure from the IEU Open GWAS project, including dried fruit intake, fresh fruit intake, raw vegetable intake, cooked vegetable intake, and cereal intake. The summary data for AD were obtained from a large GWAS meta-analysis containing 71,880 cases and 383,378 controls. RESULTS: Increased intake of dried fruits was associated with a reduced risk of AD (IVW: OR = 0.88, 95CI = 0.82-0.95). No causal association was found between the intake of other foods and AD. CONCLUSION: This MR study suggests that genetically predicted increased intake of dried fruits is a causal protective factor for AD.

Research on the application of inertially stabilized platform in the dynamic measurement of cold atomic gravimeter.

Dynamic gravity field measurement based on the cold atom absolute gravity measurement system has important applications in geological exploration, gravity field mapping and other fields. The inertial stabilized platform is the key component of the dynamic cold atom absolute gravity measurement system, which can isolate the interference of carrier angle motion and keep the atomic gravimeter probe in the horizontal attitude during the measurement process. In this paper, according to the dynamic measurement requirements of atomic gravimeter, a high-precision two-axis inertial stabilized platform system is designed. The relationship between attitude angle and gravity measurement error is analyzed, and the stability of the system is enhanced by lead-lag method. Then the static vertical vibration power spectrum of the platform is measured to consider its influence on dynamic gravity measurement. Finally, a dynamic gravity test experiment was conducted in the Yellow Sea to verify the attitude control accuracy of the platform, and the attitude data of the platform under different heading were evaluated. The attitude standard deviation of the platform was better than 4 × 10-5 rad, and the absolute gravity standard deviation of the linear round-trip measurement reached 1.49 mGal. The experimental data show that the inertial stabilized platform can meet the dynamic measurement requirements of the cold atom gravimeter.

Causal relationship between diet and knee osteoarthritis: A Mendelian randomization analysis.

BACKGROUND: Knee osteoarthritis (KOA) is a common disabling joint disease that affects millions of people worldwide. Diet may play a role in the etiology and progression of KOA, but evidence for a causal relationship is limited. We aimed to investigate the causal impact of dietary intake on KOA risk using Mendelian randomization (MR). METHODS: We used summary-level data from genome-wide association studies (GWAS) including dietary intake (n = 335, 394-462, 342), and KOA (n = 403, 124). We selected 6-77 genetic variants as instrumental variables for 18 dietary factors, including processed meat, poultry, beef, oily fish, non-oily fish, pork, lamb, frequency of alcohol intake, alcoholic beverages, tea, coffee, dried fruit, cereals, cheese, bread, cooked vegetables, salad/raw vegetables, and fresh fruit. We performed univariate and multivariate MR analyses to estimate the causal effect of each dietary factor on KOA risk. We also performed some sensitivity analyses to assess the validity of the MR hypothesis. RESULTS: We found that higher coffee intake was associated with increased KOA risk, whereas higher intake of dried fruits, grains, cheese, and oily fish was associated with reduced KOA risk. After multivariate adjustment, we found that coffee and oily fish intake may affect KOA through obesity, body mass index (BMI), diabetes, hypertension, and prolonged standing. Sensitivity analyses did not reveal any evidence of pleiotropy. CONCLUSIONS: Our study provides new causal evidence that dietary intake may influence KOA risk. Specifically, we suggest that increased intake of dried fruits, grains, cheese, and oily fish and decreased coffee intake may be beneficial in preventing and mitigating KOA. further studies are needed to elucidate the underlying mechanisms and to confirm our findings in different populations.

Efficacy of fertility-sparing treatment with LNG-IUS is associated with different ProMisE subtypes of endometrial carcinoma or atypical endometrial hyperplasia.

OBJECTIVE: To determine whether proactive molecular risk classifier for endometrial cancer (ProMisE) could be used to assess the prognosis of patients with atypical endometrial hyperplasia (AEH) or early-stage endometrial cancer (EC) treated with levonorgestrel-releasing intrauterine system (LNG-IUS). METHODS: A retrospective cohort study was conducted among 93 AEH or early-stage EC patients who received LNG-IUS to preserve fertility . By immunohistochemistry and gene sequencing, 4 subtypes of ProMisE were identified (p53 wild type [p53 wt], mismatch repair-deficient [MMRd], p53-abnormal, and POLE-mutated). The primary outcome was the time to complete response (CR) after LNG-IUS therapy. Secondary outcomes included the recurrence rate after CR and success rate of conception. RESULTS: Among the 93 patients, 15 (16.1%) were classified as MMRd, 6 (6.5%) as POLE-mutated, 5 (5.4%) as p53-abnormal, and 67 (72.0%) as p53 wt. Comparison of serum cancer antigen 125, family history of tumor, and positive rates of programmed cell death 1 ligand 1 protein and Ki67 protein in 4 groups showed statistically significant differences (p<0.05). Patients with the p53-abnormal subtype had the lowest overall CR rate (40%) and the highest recurrence rate (2/2). Patients with POLE-mutated subtype had the best prognosis, and all 6 patients achieved CR. When patients achieved complete remission, assisted reproductive technology was more likely to help them conceive than natural conception (p<0.05). CONCLUSION: Patients with early-stage EC or AEH who are more likely to benefit from fertility-sparing treatment can be identified using ProMisE classifier. Patients with POLE-mutated are suitable for fertility-sparing treatment with LNG-IUS.

Diet and risk of low back pain: a Mendelian randomization analysis.

PURPOSE: Previous epidemiological and other studies have shown an association between diet and low back pain (LBP). This study aimed to investigate the causal relationship between diet and LBP using a Mendelian randomization (MR) approach. METHODS: The three main methods in this study were weighted median, MR-Egger, and inverse variance weighting (IVW). We utilized MR-PRESSO to eliminate abnormal SNPs. Additionally, tests for pleiotropy and heterogeneity were conducted. Utilizing IVW and MR-Egger's Cochran's Q test, heterogeneity was evaluated. MR-Egger intercepts were used in pleiotropy tests. A leave-one-out analysis was also used to evaluate the stability of the study's findings. RESULTS: The frequency of alcohol intake was associated with an increased risk of LBP. Increased processed meat intake, dried fruit intake, cereal intake, and tea intake were causally associated with a decreased risk of LBP (alcohol intake frequency: odds ratio (OR) = 1.28; 95% confidence interval (CI), 1.11-1.47; P = 0.0006; processed meat intake: OR = 0.60, 95%CI 0.39-0.92, P = 0.019; dried fruit intake: OR = 0.43, 95%CI 0.29-0.66, P = 0.00008; cereal intake: OR = 0.62, 95%CI 0.42-0.92, P = 0.018; tea intake: OR = 0.75, 95%CI 0.58-0.97, P = 0.029). Heterogeneity and pleiotropy were also not found in the sensitivity analysis. The leave-one-out analysis also showed more robust results. Other dietary intakes were not causally associated with LBP. CONCLUSIONS: This two-sample MR study found that frequency of alcohol intake was associated with an increased risk of LBP, and intake of processed meat, dried fruit, cereals, and tea was associated with a decreased risk of LBP. Moreover, no causal relationship was found with LBP in the other 13 diets.

Causal Association between Tea Intake and Acute Cerebrovascular Events: A Multivariate Mendelian Randomized Study in European Populations.

BACKGROUND: Numerous research works have investigated the association between tea consumption and the risk of acute cerebrovascular events; however, the results are inconsistent. OBJECTIVES: We used Mendelian randomization (MR) to evaluate the causal association between tea intake and several acute cerebrovascular events, including any ischemic stroke, large atherosclerotic stroke (LAS), cardiogenic embolic stroke (CES), small vessel stroke (SVS), intracranial hemorrhage (ICH), and subarachnoid hemorrhage (SAH). METHODS: We obtained summary genome-wide association study (GWAS) data on tea intake and acute cerebrovascular events in populations of European ancestry. The GWAS on tea intake is derived from the UK Biobank, where we have chosen single-nucleotide polymorphisms (SNPs) closely associated with it as instrumental variables. We also obtained summary data on ischemic stroke from a GWAS meta-analysis, as well as summary data on ICH and SAH from the FinnGen study. We first explored the causal association between tea intake and several acute cerebrovascular events using univariate Mendelian randomization (UVMR), and then further assessed the causal association between tea intake and SVS using multivariate Mendelian randomization (MVMR) corrected for multiple confounders. RESULTS: In UVMR, genetically predicted increases in tea intake were linked to a lower risk of SVS (OR: 0.58; 95% CI: 0.39, 0.86). There was no causal association between tea intake and the risk of other acute cerebrovascular events. In the MVMR, our results show that there was still a significant causal association between drinking tea and SVS, after adjusting body mass index, total cholesterol, low-density lipoprotein cholesterol, diabetes, hypertension, smoking, and alcohol consumption. CONCLUSION: This MR study provides new genetic evidence that increased tea intake reduces the risk of SVS in the European population. However, possibly because of limited statistical power, the study did not find that tea consumption reduced the risk of several other acute cerebrovascular events.

Enhancing Targeted Therapy in Hepatocellular Carcinoma through a pH-Responsive Delivery System: Folic Acid-Modified Polydopamine-Paclitaxel-Loaded Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Nanoparticles.

Currently, there is an inherent contradiction between the multifunctionality and excellent biocompatibility of anticancer drug nanocarriers, which limits their application. Therefore, to overcome this limitation, we aimed to develop a biocompatible drug delivery system for the treatment of hepatocellular carcinoma (HCC). In this study, we employed poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) as the fundamental framework of the nanocarrier and utilized the emulsion solvent evaporation method to fabricate nanoparticles loaded with paclitaxel (PTX), known as PTX-PHBV NPs. To enhance the tumor-targeting capability, a dopamine self-polymerization strategy was employed to form a pH-sensitive coating on the surface of the nanoparticles. Then, folic acid (FA)-targeting HCC was conjugated to the nanoparticles with a polydopamine (PDA) coating by using the Michael addition reaction, resulting in the formation of HCC-targeted nanoparticles (PTX-PHBV@PDA-FA NPs). The PTX-PHBV@PDA-FA NPs were characterized and analyzed by using dynamic light scattering, scanning electron microscopy, fourier-transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. Encouragingly, PTX-PHBV@PDA-FA NPs exhibited remarkable anticancer efficacy in an HCC xenograft mouse model. Furthermore, compared to raw PTX, PTX-PHBV@PDA-FA NPs showed less toxicity in vivo. In conclusion, these results demonstrate the potential of PTX-PHBV@PDA-FA NPs for HCC treatment and biocompatibility.

Causal relationship between rheumatoid arthritis and hypothyroidism or hyperthyroidism: a bidirectional two-sample univariable and multivariable Mendelian randomization study.

Objective: The causal relationship between Rheumatoid arthritis (RA) and hypothyroidism/hyperthyroidism remains controversial due to the limitations of conventional observational research, such as confounding variables and reverse causality. We aimed to examine the potential causal relationship between RA and hypothyroidism/hyperthyroidism using Mendelian randomization (MR). Method: We conducted a bidirectional two-sample univariable analysis to investigate the potential causal relationship between hypothyroidism/hyperthyroidism and RA. Furthermore, we performed a multivariate analysis to account for the impact of body mass index (BMI), smoking quantity, and alcohol intake frequency. Results: The univariable analysis indicated that RA has a causative influence on hypothyroidism (odds ratio [OR]=1.07, 95% confidence interval [CI]=1.01-1.14, P=0.02) and hyperthyroidism (OR=1.32, 95% CI=1.15-1.52, P<0.001). When hypothyroidism/hyperthyroidism was considered as an exposure variable, we only observed a causal relationship between hypothyroidism (OR=1.21, 95% CI=1.05-1.40, P=0.01) and RA, whereas no such connection was found between hyperthyroidism (OR=0.91, 95% CI=0.83-1.01, P=0.07) and RA. In the multivariate MR analyses, after separately and jointly adjusting for the effects of daily smoking quantity, alcohol intake frequency, and BMI, the causal impact of RA on hypothyroidism/hyperthyroidism and hypothyroidism on RA remained robust. However, there is no evidence to suggest a causal effect of hyperthyroidism on the risk of RA (P >0.05). Conclusion: Univariate and multivariate MR analyses have validated the causal association between RA and hypothyroidism/hyperthyroidism. Hypothyroidism confirmed a causal relationship with RA when employed as an exposure variable, whereas no such relationship was found between hyperthyroidism and RA.

Serum cell division cycle 42 reflects the treatment response and survival in patients with advanced cervical cancer who receive immune checkpoint inhibitor treatment.

Cell division cycle 42 (CDC42) regulates immune escape, which predicts immune checkpoint inhibitor (ICI) treatment response in several types of cancer. The present study aimed to evaluate the potential of serum CDC42 in predicting the ICI treatment outcome in patients with advanced cervical cancer. A total of 46 patients with advanced cervical cancer who received ICI treatment with or without antiangiogenic agents were enrolled. Serum CDC42 was detected in all patients before treatment (baseline) and following two treatment cycles by enzyme-linked immunosorbent assay. CDC42 at baseline was elevated in patients with target lesion size ≥5 cm (P=0.020), pelvis metastasis (P=0.031) and lung metastasis (P=0.043). Following treatment, the objective response rate (ORR) and disease control rate (DCR) were 30.4 and 78.3%, respectively. Meanwhile, the median progression-free survival (PFS) and overall survival (OS) were 5.8 and 13.1 months. CDC42 at baseline was decreased in patients achieving ORR (P=0.042) but not DCR (P=0.055). PFS (P=0.006) and OS (P=0.019) were decreased in patients with baseline CDC42 ≥600 pg/ml. After two treatment cycles, CDC42 was generally reduced (P<0.001). CDC42 following two treatment cycles was more significantly decreased in patients with ORR (P=0.032) and DCR (P=0.019). Multivariate Cox's regression analysis showed that CDC42 ≥600 pg/ml following two treatment cycles was associated with the shorter PFS (P=0.022, hazard ratio=2.469) and OS (P=0.013, hazard ratio=4.166). Serum CDC42 was reduced after treatment; high expression following treatment reflected a lower possibility of achieving treatment response and poorer survival in patients with advanced cervical cancer.

Fecal calprotectin as a non-invasive marker for the prediction of post-necrotizing enterocolitis stricture.

PURPOSE: This study aimed to evaluate the clinical utility of fecal calprotectin (FC) levels during the necrotizing enterocolitis (NEC) episode to predict the onset of post-NEC intestinal stricture. METHODS: The medical records of patients with NEC treated from April 2020 to April 2022 were recorded for this study. FC was quantified at the acute phase of NEC. FC levels were compared in patients with or without intestinal stricture. Receiver operating characteristics (ROC) analysis was constructed to determine optimal cut-offs of FC for post-NEC intestinal stricture. RESULTS: A total of 50 infants with NEC were enrolled in this study and 14 (28%) of them eventually developed intestinal stricture. All children with intestinal stricture underwent one-stage surgery and all made it through the follow-up period alive. The median FC level was 1237.55 (741.25, 1378.80) ug/g in patients with intestinal stricture and it was significantly higher than that in the non-stricture group [158.30 (76.23, 349.13) ug/g, P < 0.001]. FC had good diagnostic accuracy for predicting intestinal stricture, according to ROC curve analysis, with an AUC area of 0.911. At an optimal cut-off value of 664.2 ug/g, sensitivity and specificity were 85.71% and 91.67%, respectively. CONCLUSION: As a non-invasive parameter, FC has excellent efficacy and accuracy in predicting post-NEC intestinal stricture. Increased FC levels at the acute phase of NEC were associated with the development of intestinal stricture.

A novel hypoxia-stimulated lncRNA HIF1A-AS3 binds with YBX1 to promote ovarian cancer tumorigenesis by suppressing p21 and AJAP1 transcription.

Hypoxia is characteristic of the ovarian tumor (OC) microenvironment and profoundly affects tumorigenesis and therapeutic response. Long noncoding RNAs (lncRNAs) play various roles in tumor progression; however, the characteristics of lncRNAs in pathological responses of the OC microenvironment are not entirely understood. Through high-throughput sequencing, lncRNA expression in hypoxia (1% O2 ) and normoxia (21% O2 ) SKOV3 cells was explored and analyzed. The 5'- and 3'-rapid amplification of complementary DNA ends was used to detect the full length of the novel HIF1A-AS3 transcript. Real-time quantitative polymerase chain reaction was used to assess HIF1A-AS3 expression in OC cells and tissues. In vitro and in vivo evaluations of the biological functions of hypoxic HIF1A-AS3 were conducted. To clarify the underlying mechanisms of HIF1A-AS3 in hypoxic OC, a dual-luciferase assay, chromatin immunoprecipitation, RNA pull-down, RNA immunoprecipitation, and RNA-sequencing were used. We used high-throughput sequencing to investigate a novel lncRNA, HIF1A-AS3, as a hypoxic candidate significantly elevated in OC cells/tissues. HIF1A-AS3 was predominantly localized in the nucleus and promoted in vitro and in vivo OC growth and tumorigenesis. Hypoxia-inducible factor 1α bound to hypoxia response elements in the HIF1A-AS3 promoter region and stimulated its expression in hypoxia. Under hypoxia, HIF1A-AS3 directly integrated with Y-Box binding protein 1 and inhibited its ability to bind to the promoters of p21 and AJAP1 to repress their transcriptional activity, thereby promoting hypoxic OC progression. Our results revealed the crucial role and mechanism of the novel hypoxic HIF1A-AS3 in the oncogenesis of OC. The novel HIF1A-AS3 could be a crucial biomarker and therapeutic target for future OC treatments.

Low expression of acyl-CoA thioesterase 13 is associated with poor prognosis in ovarian serous cystadenocarcinoma.

Objective: Acyl-CoA thioesterase 13 (ACOT13) encodes a member of the thioesterase superfamily. It has not been reported in ovarian cancer. This research aimed at evaluating the expression and prognostic value of ACOT13 in ovarian serous cystadenocarcinoma (OSC). Methods: We extracted and analyzed TCGA, GEPIA, THPA, GTEx, miRWalk, and GDSC databases to investigate the potential carcinogenic mechanism of ACOT13 in OSC, including the correlation of ACOT13 with prognosis, immune checkpoint, tumor mutational burden (TMB), and 50% inhibition concentration (IC50) score. The incidence of endpoint events was compared with Kaplan-Meier survival analysis. Independent prognostic factors for OSC were evaluated with univariate and multivariate Cox regression analyses, and a nomogram was established. Results: The expression of ACOT13 was increased in OSC and correlated with tumor stage, with higher expression in stages I and II than in stages III and IV. Besides, it was observed that low expression of ACOT13 is correlated with poor overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS) in patients with OSC. There was a positive correlation between ACOT13 expression and immune checkpoint sialic acid-binding Ig-like lectin (SIGLEC) 15 and TMB. Patients with low ACOT13 expression had higher cisplatin IC50 scores. Conclusion: ACOT13 is an independent prognostic factor and a promising clinical target for OSC. In the future, the carcinogenic mechanism and clinical application value of ACOT13 in ovarian cancer need to be further studied.

Causal relationship between ischemic stroke and its subtypes and frozen shoulder: a two-sample Mendelian randomization analysis.

Background: Previous epidemiological and other studies have shown an association between ischemic stroke (IS) and frozen shoulder (FS). However, the causal relationship between them remains unclear. Therefore, the present study aimed to investigate the causal relationship between IS and FS using a two-sample Mendelian randomization method. Methods: Our research was divided into two stages: discovery and replication. The data were extracted from publicly available genome-wide association studies (GWAS). We selected a large sample of IS (n = 440, 328) and its subtypes (large-artery atherosclerotic stroke (LAS), cardioembolic stroke (CES), and stroke caused by small-vessel disease (SVS) and lacunar stroke (n = 254, 959) as exposure data. Additionally, we selected a large sample of FS as outcome data (n = 451, 099). Inverse variance weighting (IVW) was applied as the primary analysis method. The weighted median, MR-Egger, simple model, and weighted model were used as complementary analysis methods to assess causal effects. Moreover, heterogeneity was analyzed using Cochran's Q-test with IVW and MR-Egger. The MR-Egger intercept and MR-PRESSO analysis methods were used for pleiotropy testing. The stability of the results was also assessed using a leave-one-out analysis. Results: In the discovery stage, the IVW approach revealed an odds ratio (OR) of 1.207 with a 95% confidence interval (CI) of 1.027-1.417 and a P-value of 0.022. This suggests a causal association between IS levels and an increased risk of FS. In the subtype studies of IS, the findings were negative. However, during the replication stage, a significant causal link was found between selected lacunar strokes and FS with an OR of 1.252, a 95% CI of 1.105-1.419, and a P-value of 0.0004. All studies had no pleiotropy or heterogeneity, and the findings were robust. Conclusions: Our study confirmed the causal relationship between any IS level and increased risk of FS. Furthermore, the same results were obtained in the replication stage with lacunar stroke as an exposure factor. However, there was no direct causal relationship between the subtypes of IS and FS. Our study provides theoretical support for shoulder care for patients with IS.

The relationship between major depression and migraine: A bidirectional two-sample Mendelian randomization study.

Background: Previous epidemiological and other studies have shown an association between major depressive disorder (MDD) and migraine. However, the causal relationship between them remains unclear. Therefore, this study aimed to investigate the causal relationship between MDD and migraine using a bidirectional, two-sample Mendelian randomization (MR) approach. Methods: Data on MDD and migraine, including subtypes with aura migraine (MA) and without aura migraine (MO), were gathered from a publicly available genome-wide association study (GWAS). Single nucleotide polymorphisms (SNPs) utilized as instrumental variables (IVs) were then screened by adjusting the intensity of the connection and removing linkage disequilibrium. To explore causal effects, inverse variance weighting (IVW) was used as the primary analysis method, with weighted median, MR-Egger, simple mode, and weighted mode used as supplementary analytic methods. Furthermore, heterogeneity and pleiotropy tests were carried out. Cochran's Q-test with IVW and MR-Egger was used to assess heterogeneity. Pleiotropy testing was carried out using the MR-Egger intercept and MR-PRESSO analysis methods. A leave-one-out analysis was also used to evaluate the stability of the findings. Finally, we used migraine (MA and MO) levels to deduce reverse causality with MDD risk. Results: Random effects IVW results were (MDD-Migraine: odds ratio (OR), 1.606, 95% confidence interval (CI), 1.324-1.949, p = 1.52E-06; MDD-MA: OR, 1.400, 95%CI, 1.067-1.8378, p = 0.015; MDD-MO: OR, 1.814, 95%CI, 1.277-2.578, p = 0.0008), indicating a causal relationship between MDD levels and increased risk of migraine (including MA and MO). In the inverse MR analysis, the findings were all negative, while in sensitivity analyses, the results were robust except for the study of MA with MDD. Conclusion: Our study confirms a causal relationship between MDD levels and increased risk of migraine, MA, and MO. There was little evidence in the reverse MR analysis to suggest a causal genetic relationship between migraine (MA and MO) and MDD risk levels.

A benchmark model for exploring the differentiation of trust in information sources in heterogeneous farmers' green behavior.

The literature reports that trust in information sources (ISs) is an important determinant of farmers' adoption of sustainable environmental practices. However, few in-depth studies have focused on the differences in trust among different ISs in heterogeneous farmers' green behavior. Therefore, it is challenging for heterogeneous farmers to design efficient and differentiated information strategies. This study proposes a benchmark model to explore differences in trust in different ISs in the application of organic fertilizers (OFs) to farmers at different scales. A total of 361 farmers of a geographically indicated agricultural product in China were evaluated to understand their trust in different ISs when adopting OFs. The results identify the differentiation of heterogeneous farmers' trust in different ISs when considering green practices. Specifically, large-scale farmers' green behavior is more likely to be influenced by trust in formal ISs (strength-weakness ratio of 1.15 for the effect of two ISs), whereas small-scale farmers' green behavior is strongly influenced by trust in informal ISs (strength-weakness ratio of 4.62 for the effect of two ISs). This difference was mainly caused by differences in farmers' information acquisition ability, level of social capital, and preference for social learning. The model and findings of this study can aid policy-makers in designing effective and differentiated information interventions for different types of farmers to maximize their adoption of sustainable environmental practices.

Novel Optofluidic Imaging System Integrated with Tunable Microlens Arrays.

Optofluidic tunable microlens arrays (MLAs) can manipulate and control light propagation using fluids. Lately, their applicability to miniature lab-on-a-chip systems is being extensively researched. However, it is difficult to incorporate 3D MLAs directly in a narrow microfluidic channel using common techniques. This has resulted in limited research on variable focal length imaging with optofluidic 3D MLAs. In this paper, we propose a method for fabricating MLAs in polydimethylsiloxane (PDMS)-based microchannels via electrohydrodynamic jet (E-jet) printing to achieve optofluidic tunable MLAs. Using this method, MLAs of diameters 15 to 80 µm can be fabricated in microfluidic channels with widths of 200 and 300 µm. By alternately using solutions with different refractive indices in the microchannel, the optofluidic microlenses exhibit reversible modulation properties while retaining the morphologies and refractive indices of the microlenses. The focal length of the resulting optofluidic chip can have threefold tunability, thereby achieving an imaging depth of approximately 450 µm. This outstanding advantage is useful in observing microspheres and cells flowing in the microfluidic system. Thus, the proposed optofluidic chip exhibits great potential for cell counting and imaging applications.

The causal relationship between 41 inflammatory cytokines and hypothyroidism: bidirectional two-sample Mendelian randomization study.

Objective: Investigating the association between inflammatory cytokines and hypothyroidism remains challenging due to limitations in traditional observational studies. In this study, we employed Mendelian randomization (MR) to assess the causal relationship between 41 inflammatory cytokines and hypothyroidism. Method: Inflammatory cytokines in 30,155 individuals of European ancestry with hypothyroidism and in a GWAS summary containing 8,293 healthy participants were included in the study for bidirectional two-sample MR analysis. We utilized inverse variance weighting (IVW), weighted median (WM), and Mendelian randomization-Egger (MR-Egger) methods. Multiple sensitivity analyses, including MR-Egger intercept test, leave-one-out analysis, funnel plot, scatterplot, and MR-PRESSO, were applied to evaluate assumptions. Results: We found evidence of a causal effect of IL-7 and macrophage inflammatory protein-1ß (MIP-1ß) on the risk of hypothyroidism, and a causal effect of hypothyroidism on several cytokines, including granulocyte colony-stimulating factor (G-CSF), IL-13, IL-16, IL-2rα, IL-6, IL-7, IL-9, interferon-γ-inducible protein 10 (IP10), monokine induced by interferon (IFN)-γ (MIG), macrophage inflammatory protein-1ß (MIP-1ß), stem cell growth factors-ß (SCGF-ß), stromal cell derived factor-1α (SDF-1α), and tumor necrosis factor-α (TNF-α). Conclusion: Our study suggests that IL-7 and MIP-1ß may play a role in the pathogenesis of hypothyroidism, and that hypothyroidism may induce a systemic inflammatory response involving multiple cytokines. These findings may have implications for the prevention and treatment of hypothyroidism and its complications. However, further experimental studies are needed to validate the causal relationships and the potential of these cytokines as drug targets.

The development and progress of health literacy in China.

Limited health literacy is a serious public health problem. It is strongly associated with increased hospital admissions and readmission, poorer self-management, and health outcomes. It can lead to poor management of chronic disease, lower health care quality, increased mortality, and higher healthcare expenditures. Understanding China's current situation and the progress of health literacy levels are critical to achieving practical solutions for improving population health. This paper intended to provide a concise overview of the key milestones and specific practices in health literacy in China. We summarized the characteristics and changing profile of health literacy from 2008 to 2020 in China. We developed an intervention framework based on social ecosystem theory for improving health literacy in China. Meanwhile, some multi-level actionable recommendations were proposed. The study revealed that China has made progress in improving health literacy in the last decades. Health literacy levels increased from 6.48% of the population in 2008 to 23.15% in 2020. Geographic disparities were substantial. The East performed better health literacy than the Central and West, and cities had higher adequate health literacy than rural areas. Social development index, age, and education level were highly associated with health literacy. A global joint effort to improve health literacy will be required. And we advocate a whole-of-society approach that involves the participation of the entire ecosystem around the targeted population.

Nano Sized Hydroxyapatite-Polylactic Acid-Vancomycin in Alleviation of Chronic Osteomyelitis.

Background: Vancomycin (VAN) is effective in inhibiting inflammatory reactions in chronic osteomyelitis (CO), while nano-hydroxyapatite (nHA) can effectively address the poor biocompatibility and high brittleness of ordinary HA and better repair bone defects. Therefore, the efficacy of nHA combined with VAN for CO with bone defects deserves further discussion. Objective: To explore the effect of VAN, which is loaded in the nanodelivery system formed by nHA and polylactic acid (PLA), in CO therapy. Methods: The stability of nHA-PLA-VAN in PBS solution at different temperatures and its effect on VAN's half-life were determined in the physicochemical property test. Immunofluorescence (IF) determined the stability and permeability of Cy3-coupled nHA-PLA-VAN in bone marrow of B6/J mice. The cultured osteoblasts were further divided into control, polyethyleneimine (PEI), and nHA-PLA groups to observe their differences in cell proliferation, mineralization, and migration capacities. And a CO mouse model was constructed to detect the anti-CO effect of nHA-PLA-VAN. Results: nHA-PLA-VAN nanocomposites maintained good stability in different acidic solutions, favoring their long-term preservation in vitro. nHA-PLA extended VAN's half-life by 6-times. In the permeation test, nHA-PLA-VAN showed significantly higher permeation efficiency than PEI, enabling it to effectively transport VAN to bone marrow tissue, thus better inhibiting bacterial activity and reducing CD4, CD8, CD19, and CD20 expression in the lesion area of CO mice. In the osteoblast experiment, nHA-PLA more effectively maintained osteoblast viability and promoted proliferation and migration, thus better repairing defective bone tissue. In the CO mouse model, nHA-PLA-VAN better inhibited inflammatory reactions, such as congestion and edema in the focus, and increased the number and thickness of bone trabeculae. Furthermore, max load, elastic load, and rigidity coefficient of the bone defect area were recovered to a great extent. Conclusion: nHA-PLA-VAN may be a better choice for future treatment of CO.