Repurposing the multiple sclerosis drug Siponimod for osteoporosis treatment.

Osteoporosis is the most common bone disorder, in which an imbalance between osteoclastic bone resorption and osteoblastic bone formation disrupts bone homeostasis. Osteoporosis management using anti-osteoclastic agents is a promising strategy; however, this remains an unmet need. Sphingosine-1-phosphate (S1P) and its receptors (S1PRs) are essential for maintaining bone homeostasis. Here, we identified that Siponimod, a Food and Drug Administration-approved S1PR antagonist for the treatment of multiple sclerosis, shows promising therapeutic effects against osteoporosis by inhibiting osteoclast formation and function. We found that Siponimod inhibited osteoclast formation in a dose-dependent manner without causing cytotoxicity. Podosome belt staining and bone resorption assays indicated that Siponimod treatment impaired osteoclast function. Western blot and qPCR assays demonstrated that Siponimod suppressed the expression of osteoclast-specific markers, including C-Fos, Nftac1, and Ctsk. Mechanistically, we validated that Siponimod downregulated receptor activator of nuclear factor kappa B ligand (RANKL)-induced Mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathways during osteoclastogenesis. Moreover, in a preclinical mouse model, Siponimod prevented ovariectomy-induced bone loss by suppressing osteoclast activity in vivo. Collectively, these results suggest that Siponimod could serve as an alternative therapeutic agent for the treatment of osteoporosis.

Prognostic factors and the role of primary debulking in operable stage IVB ovarian cancer with supraclavicular lymph node metastasis: a retrospective study in Chinese patients.

BACKGROUND: Recent studies showed heterogeneity in stage IVB patients. However, few studies focused on the prognosis of supraclavicular metastatic ovarian cancer. This study aimed to explore the prognostic factors and the role of primary debulking in IVB ovarian cancer patients with supraclavicular lymph node metastasis. METHODS: We retrospectively analyzed patients newly diagnosed as primary epithelial ovarian cancer with supraclavicular lymph node metastasis from January 2015 to July 2020. Supraclavicular lymph node metastasis was defined as either the pathological diagnosis by supraclavicular lymph node biopsy, or the radiological diagnosis by positron emission tomography-computed tomography (PET-CT). RESULTS: In 51 patients, 37 was diagnosed with metastatic supraclavicular lymph nodes by histology, 46 by PET-CT, and 32 by both methods. Forty-four (86.3%) with simultaneous metastatic paraaortic lymph nodes (PALNs) by imaging before surgery or neoadjuvant chemotherapy were defined as "continuous-metastasis type", while the other 7 (13.7%) defined as "skip-metastasis type". Nineteen patients were confirmed with metastatic PALNs by histology. Thirty-four patients were investigated for BRCA mutation, 17 had germline or somatic BRCA1/2 mutations (g/sBRCAm). With a median follow-up of 30.0 months (6.3-63.4 m), 16 patients (31.4%) died. The median PFS and OS of the cohort were 17.3 and 48.9 months. Survival analysis showed that "continuous-metastasis type" had longer OS and PFS than "skip-metastasis type" (OS: 50.0/26.6 months, PFS: 18.5/7.2months, p=0.005/0.002). BRCA mutation carriers also had longer OS and PFS than noncarriers (OS: 57.4 /38.5 m, p=0.031; PFS: 23.6/15.2m, p=0.005). Multivariate analysis revealed only metastatic PALNs was independent prognostic factor for OS (p=0.040). Among "continuous-metastasis type" patients, 22 (50.0%) achieved R0 abdominopelvic debulking, who had significantly longer OS (55.3/42.3 months, p =0.034) than those with residual abdominopelvic tumors. CONCLUSIONS: In stage IVB ovarian cancer patients with supraclavicular lymph nodes metastasis, those defined as "continuous-metastasis type" with positive PALNs had better prognosis. For them, optimal abdominopelvic debulking had prognostic benefit, although metastatic supraclavicular lymph nodes were not resected. Higher BRCA mutation rate than the general population of ovarian cancer patients was observed in patients with IVB supraclavicular lymph node metastasis, leading to better survival as expected.

Non-rigid scene reconstruction of deformable soft tissue with monocular endoscopy in minimally invasive surgery.

PURPOSE: The utilization of image-guided surgery has demonstrated its ability to improve the precision and safety of minimally invasive surgery (MIS). Non-rigid scene reconstruction is a challenge in image-guided system duo to uniform texture, smoke, and instrument occlusion, etc. METHODS: In this paper, we introduced an algorithm for 3D reconstruction aimed at non-rigid surgery scenes. The proposed method comprises two main components: firstly, the front-end process involves the initial reconstruction of 3D information for deformable soft tissues using embedded deformation graph (EDG) on the basis of dual quaternions, enabling the reconstruction without the need for prior knowledge of the target. Secondly, the EDG is integrated with isometric nonrigid structure from motion (Iso-NRSFM) to facilitate centralized optimization of the observed map points and camera motion across different time instances in deformable scenes. RESULTS: For the quantitative evaluation of the proposed method, we conducted comparative experiments with both synthetic datasets and publicly available datasets against the state-of-the-art 3D reconstruction method, DefSLAM. The test results show that our proposed method achieved a maximum reduction of 1.6 mm in average reconstruction error compared to method DefSLAM across all datasets. Additionally, qualitative experiments were performed on video scene datasets involving surgical instrument occlusions. CONCLUSION: Our method proved to outperform DefSLAM on both synthetic datasets and public datasets through experiments, demonstrating its robustness and accuracy in the reconstruction of soft tissues in dynamic surgical scenes. This success highlights the potential clinical application of our method in delivering surgeons with critical shape and depth information for MIS.

Adaptive Multi-dimensional Weighted Network with Category-aware Contrastive Learning for Fine-grained Hand Bone Segmentation.

Accurately delineating and categorizing individual hand bones in 3D ultrasound (US) is a promising technology for precise digital diagnostic analysis. However, this is a challenging task due to the inherent imaging limitations of the US and the insignificant feature differences among numerous bones. In this study, we have proposed a novel deep learning-based solution for pediatric hand bone segmentation in the US. Our method is unique in that it allows for effective detailed feature mining through an adaptive multi-dimensional weighting attention mechanism. It innovatively implements a category-aware contrastive learning method to highlight inter-class semantic feature differences, thereby enhancing the category discrimination performance of the model. Extensive experiments on the challenging pediatric clinical hand 3D US datasets show the outstanding performance of the proposed method in segmenting thirty-eight bone structures, with the average Dice coefficient of 90.0%. The results outperform other state-of-the-art methods, demonstrating its effectiveness in fine-grained hand bone segmentation. Our method will be globally released as a plugin in the 3D Slicer, providing an innovative and reliable tool for relevant clinical applications. The source codes are available at https://github.com/Bolun-Z/HandAISegmentation.

The development of a novel navigation system for reverse shoulder arthroplasty and its accuracy: a phantom and cadaveric study.

PURPOSE: Reverse shoulder arthroplasty has demonstrated excellent clinical efficacy for patients with shoulder joint diseases and is increasingly in demand. Traditional surgery faces challenges such as limited exposed surfaces and a narrow field of vision, leading to a shorter prosthesis lifespan and a higher risk of complications. In this study, an optical navigation system was proposed to assist surgeons in real-time tracking of the surgical scene. METHODS: Our optical navigation system was developed using the NDI Polaris Spectra device and several open-source platforms. The first step involved using the preoperative medical image to plan screw implantation paths. Real-time tracking of the patient phantom or cadaver and the surgical instrument was achieved through registration and calibration algorithms. Surgeons were guided on drilling through visualization methods. Postoperative results were compared with the planned implantation paths, and an algorithm was introduced to correct errors caused by the incorrect beginning points. RESULTS: Experiments involved three scapula cadavers and their corresponding phantoms with identical anatomy. For each experiment, three holes were completed with drills with diameters of 3.2 mm and 8.0 mm, respectively. Comparisons between the postoperative actual screw implantation paths and the preoperative planned implantation paths revealed an entry error of 1.05 ± 0.15 mm and an angle error of 2.47 ± 0.55° for phantom experiments. For cadaver experiments, the entry error was 1.53 ± 0.22 mm, and the angle error was 4.91 ± 0.78°. CONCLUSION: Our proposed optical navigation system successfully achieved real-time tracking of the surgical site, encompassing the patient phantom or cadaver and surgical instrument, thereby aiding surgeons in achieving precise surgical outcomes. Future study will explore the integration of robots to further enhance surgical efficiency and effectiveness.

Clinical and pathological features of 52 patients with glomerulonephritis with dominant C3. / C3沉积为主的肾小球肾炎52ä¾‹ä¸´åºŠä¸Žç— ç†ç‰¹å¾.

OBJECTIVES: With the in-depth study of complement dysregulation, glomerulonephritis with dominant C3 has received increasing attention, with a variety of pathologic types and large differences in symptoms and prognosis between pathologic types. This study analyzes the clinical, pathological, and prognostic characteristics of different pathological types of glomerulonephritis with dominant C3, aiming to avoid misdiagnosis and missed diagnoses. METHODS: The clinical, pathological, and follow-up data of 52 patients diagnosed as glomerulonephritis with dominant C3 by renal biopsy from June 2013 to October 2022 were retrospectively analyzed. According to the clinical feature and results of pathology, 15 patients with post-infectious glomerulonephritis (PIGN) and 37 patients with of non-infectious glomerulonephritis (N-PIGN) were classified. N-PIGN subgroup analysis was performed, and 16 patients were assigned into a C3-alone-deposition group and 21 in a C3-dominant-deposition group, or 27 in a C3 glomerulopathy (C3G) group and 10 in a non-C3 nephropathy (N-C3G) group. RESULTS: The PIGN group had lower creatinine values (84.60 µmol/L vs179.62 µmol/L, P=0.001), lower complement C3 values (0.36 g/L vs0.74 g/L, P<0.001) at biopsy, and less severe pathological chronic lesions compared with the N-PIGN group. In the N-PIGN subgroup analysis, the C3-dominant-deposition group had higher creatinine values (235.30 µmol/L vs106.70 µmol/L, P=0.004) and higher 24-hour urine protein values (4 025.62 mg vs1 981.11 mg, P=0.037) than the C3-alone-deposition group. The prognosis of kidney in the PIGN group (P=0.049), the C3-alone-deposition group (P=0.017), and the C3G group (P=0.018) was better than that in the N-PIGN group, the C3-dominant-deposition group, and the N-C3G group, respectively. CONCLUSIONS: Glomerulonephritis with dominant C3 covers a variety of pathological types, and PIGN needs to be excluded before diagnosing C3G because of considerable overlap with atypical PIGN and C3G; in addition, the deposition of C1q complement under fluorescence microscope may indicate poor renal prognosis, and relevant diagnosis, treatment, and follow-up should be strengthened.

Proteogenomic insights into early-onset endometrioid endometrial carcinoma: predictors for fertility-sparing therapy response.

Endometrial carcinoma remains a public health concern with a growing incidence, particularly in younger women. Preserving fertility is a crucial consideration in the management of early-onset endometrioid endometrial carcinoma (EEEC), particularly in patients under 40 who maintain both reproductive desire and capacity. To illuminate the molecular characteristics of EEEC, we undertook a large-scale multi-omics study of 215 patients with endometrial carcinoma, including 81 with EEEC. We reveal an unexpected association between exposome-related mutational signature and EEEC, characterized by specific CTNNB1 and SIGLEC10 hotspot mutations and disruption of downstream pathways. Interestingly, SIGLEC10Q144K mutation in EEECs resulted in aberrant SIGLEC-10 protein expression and promoted progestin resistance by interacting with estrogen receptor alpha. We also identified potential protein biomarkers for progestin response in fertility-sparing treatment for EEEC. Collectively, our study establishes a proteogenomic resource of EEECs, uncovering the interactions between exposome and genomic susceptibilities that contribute to the development of primary prevention and early detection strategies for EEECs.

Using Apparent Diffusion Coefficient (ADC) of Endometrial Cancer MRI to Determine P53 Molecular Subtypes.

BACKGROUND: Endometrial Cancer (EC) is a highly heterogeneous cancer comprising both histological and molecular subtypes. Using a non-invasive modality method to trigger these subtypes as early as possible can aid clinicians in establishing individualized treatment. PURPOSE: The study aimed to clarify the value of the Apparent Diffusion Coefficient (ADC) of EC MRI in determining molecular subtypes. MATERIAL AND METHODS: We retrospectively recruited 109 patients with pathologically proven EC (78 endometrioid cancers and 31 non-endometrioid cancers) with available molecular classification from a tertiary centre. MRI was prospectively performed a month prior to surgery; images were blindly interpreted by two experienced radiologists with consensus reading. The ADC value was measured by an experienced radiologist on the commercially available processing workstation. Interoperator measurement consistency was calculated. RESULTS: Our sample comprised 17 PLOE, 32 MSI-H, 31 NSMP, and 29 P53abn ECs. Clinical information did not differ significantly among the groups. The maximum diameter and volume of the lesions differed among the groups. The ADC value in the maximal area (ADCarea) or region of interest (ROI, ADCroi) in the P53abn group was higher than that in the other groups (894.0 ±12.6 and 817.5 ± 83.3 x10-6 mm2/s). The ADC mean values were significantly different between the P53abn group and the other groups (P = 0.000). The nomogram showed the highest discriminative ability to distinguish P53abn EC from other types (AUC: 0.859). CONCLUSION: Our results have suggested the quantitative MR characteristics (ADC values) derived from preoperative EC MRI to provide useful information in preoperatively determining P53abn cancer.

Investigating the efficacy of an exopolysaccharide (EPS)-producing strain Lactiplantibacillus plantarum L75 on oat silage fermentation at different temperatures.

This study investigates the effectiveness of an exopolysaccharide (EPS)-producing strain (Lactiplantibacillus plantarum L75) alone or in combination with Saccharomyces cerevisiae on the fermentation characteristics, antioxidant capacities and microbial community successions of oat silage stored at various temperatures. A rapid decrease in pH and lactic acid accumulation was observed in silages treated with L. plantarum and S. cerevisiae (LS) as early as 3 days of ensiling (p < 0.05). Over the ensiling period of 7-60 days, L. plantarum (L)-inoculated groups showed the lowest pH, lowest ammonia nitrogen and the highest amount of lactic acid regardless of the storage temperatures. When the oat silage was stored at 15°C, LS-inoculated group exhibited a higher superoxide dismutase (SOD) activity than control and L-inoculated group. Furthermore, the proportion of Lactiplantibacillus in the combined inoculation group increased by 65.42% compared to the L-inoculated group (33.26%). Fungal community data revealed abundant Penicillium carneum in the control and L-inoculated groups stored at 15°C. Conclusively, these results showed that combined inoculation of L. plantarum L75 and S. cerevisiae improved the fermentation quality of oat silage at 15°C, thus proposing a technique for enhancing the fermentation quality of silage in regions with low temperatures during harvest season.

From Coarse to Fine: Non-Rigid Sparse-Dense Registration for Deformation-Aware Liver Surgical Navigation.

OBJECTIVE: Intraoperative liver deformation poses a considerable challenge during liver surgery, causing significant errors in image-guided surgical navigation systems. This study addresses a critical non-rigid registration problem in liver surgery: the alignment of intrahepatic vascular trees. The goal is to deform the complete vascular shape extracted from preoperative Computed Tomography (CT) volume, aligning it with sparse vascular contour points obtained from intraoperative ultrasound (iUS) images. Challenges arise due to the intricate nature of slender vascular branches, causing existing methods to struggle with accuracy and vascular self-intersection. METHODS: We present a novel non-rigid sparse-dense registration pipeline structured in a coarse-to-fine fashion. In the initial coarse registration stage, we introduce a parametrization deformation graph and a Welsch function-based error metric to enhance convergence and robustness of non-rigid registration. For the fine registration stage, we propose an automatic curvature-based algorithm to detect and eliminate overlapping regions. Subsequently, we generate the complete vascular shape using posterior computation of a Gaussian Process Shape Model. RESULTS: Experimental results using simulated data demonstrate the accuracy and robustness of our proposed method. Evaluation results on the target registration error of tumors highlight the clinical significance of our method in tumor location computation. Comparative analysis against related methods reveals superior accuracy and competitive efficiency of our approach. Moreover, Ex vivo swine liver experiments and clinical experiments were conducted to evaluate the method's performance. CONCLUSION: The experimental results itasize the accurate and robust performance of our proposed method. SIGNIFICANCE: Our proposed non-rigid registration method holds significant application potential in clinical practice.

Diabetes Distress Among Patients Undergoing Surgery for Diabetic Retinopathy and Associated Factors: A Cross-Sectional Survey.

Background: Diabetes distress (DD) is a negative emotion related to diabetes management and a predictor of depression; it affects diabetic retinopathy (DR) patients' quality of life and disease outcomes. The prevalence of DD was higher in patients undergoing surgery for DR. However, few studies have been conducted on DD in DR surgery patients. The present study aims to investigate the status of DD in DR surgery patients and identify factors associated with DD. Methods: Using a convenience sampling method, 210 DR surgery patients who were admitted to 2 tertiary-level hospitals in Wenzhou City (Zhejiang Province) and Zhengzhou City (Henan Province) from February to June 2023 were selected as research subjects. A questionnaire collecting demographic and disease-related information, the Diabetes Distress Scale, the Summary of Diabetes Self-Management Activities, the Family Care Index Scale, and the Social Support Rating Scale were used to collect data. Statistical analyses included descriptive statistics, t tests, ANOVAs, Pearson's correlation analyses and stepwise multiple linear regression. This study is reported according to the STROBE guidelines. Results: In total, 156 out of 210 (74.29%) DR surgery patients experienced DD, with an average score of 2.13±0.63. The results of the stepwise multiple regression analysis showed that residential location, employment status, self-management level, family support, and social support were significantly associated with DD. These variables accounted for 30.6% of the total variation in DD. Conclusions: DR surgery patients exhibit moderate levels of distress. Health care professionals should pay attention to DD in DR surgery patients and develop targeted interventions to improve the self-management ability of these patients, increase their family support and social support to reduce their DD levels.

Canagliflozin inhibits PASMCs proliferation via regulating SGLT1/AMPK signaling and attenuates artery remodeling in MCT-induced pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) was a devastating disease characterized by artery remodeling, ultimately resulting in right heart failure. The aim of this study was to investigate the effects of canagliflozin (CANA), a sodium-glucose cotransporter 2 inhibitor (SGLT2i) with mild SGLT1 inhibitory effects, on rats with PAH, as well as its direct impact on pulmonary arterial smooth muscle cells (PASMCs). PAH rats were induced by injection of monocrotaline (MCT) (40 mg/kg), followed by four weeks of treatment with CANA (30 mg/kg/day) or saline alone. Pulmonary artery and right ventricular (RV) remodeling and dysfunction in PAH were alleviated with CANA, as assessed by echocardiography. Hemodynamic parameters and structural of pulmonary arteriole, including vascular wall thickness and wall area, were reduced by CANA. RV hypertrophy index, cardiomyocyte hypertrophy, and fibrosis were decreased with CANA treatment. PASMCs proliferation was inhibited by CANA under stimulation by platelet-derived growth factor (PDGF)-BB or hypoxia. Activation of AMP kinase (AMPK) was induced by CANA treatment in cultured PASMCs in a time- and concentration-dependent manner. These effects of CANA were attenuated when treatment with compound C, an AMPK inhibitor. Abundant expression of SGLT1 was observed in PASMCs and pulmonary arteries, while SGLT2 expression was undetectable. SGLT1 increased in response to PDGF-BB or hypoxia stimulation, while PASMCs proliferation was inhibited and beneficial effects of CANA were counteracted by knockdown of SGLT1. Our research demonstrated for the first time that CANA inhibited the proliferation of PASMCs by regulating SGLT1/AMPK signaling and thus exerted an anti-proliferative effect on MCT-induced PAH.

The combined effects of azoxystrobin and different aged polyethylene microplastics on earthworms (Eisenia fetida): A systematic evaluation based on oxidative damage and intestinal function.

Pesticides and microplastics are common pollutants in soil environments, adversely affecting soil organisms. However, the combined toxicological effects of aged microplastics and pesticides on soil organisms are still unclear. In this study, we systematically studied the toxicological effects of azoxystrobin and four different aged polyethylene (PE) microplastics on earthworms (Eisenia fetida). The purpose was to evaluate the effects of aging microplastics on the toxicity of microplastics-pesticides combinations on earthworms. The results showed that different-aged PE microplastics promoted azoxystrobin accumulation in earthworms. Meanwhile, combined exposure to azoxystrobin and aged PE microplastics decreased the body weight of earthworms. Besides, both single and combined exposure to azoxystrobin and aged PE microplastics could lead to oxidative damage in earthworms. Further studies revealed that azoxystrobin and aged PE microplastics damage the intestinal structure and function of earthworms. Additionally, the combination of different aged PE microplastics and azoxystrobin was more toxic on earthworms than single exposures. The PE microplastics subjected to mechanical wear, ultraviolet radiation, and acid aging exhibited the strongest toxicity enhancement effects on earthworms. This high toxicity may be related to the modification of PE microplastics caused by aging. In summary, these results demonstrated the enhancing effects of aged PE microplastics on the toxicity of pesticides to earthworms. More importantly, aged PE microplastics exhibited stronger toxicity-enhancing effects in the early exposure stages. This study provides important data supporting the impact of different aged PE microplastics on the environmental risks of pesticides.

A hybrid robotic system for zygomatic implant placement based on mixed reality navigation.

BACKGROUNDS: Zygomatic implant (ZI) placement surgery is a viable surgical option for patients with severe maxillary atrophy and insufficient residual maxillary bone. Still, it is difficult and risky due to the long path of ZI placement and the narrow field of vision. Dynamic navigation is a superior solution, but it presents challenges such as requiring operators to have advanced skills and experience. Moreover, the precision and stability of manual implantation remain inadequate. These issues are anticipated to be addressed by implementing robot-assisted surgery and achieved by introducing a mixed reality (MR) navigation-guided hybrid robotic system for ZI placement surgery. METHODS: This study utilized a hybrid robotic system to perform the ZI placement surgery. Our first step was to reconstruct a virtual 3D model from preoperative cone-beam CT (CBCT) images. We proposed a series of algorithms based on coordinate transformation, which includes image-phantom registration, HoloLens-tracker registration, drill-phantom calibration, and robot-implant calibration, to unify all objects within the same coordinate system. These algorithms enable real-time tracking of the surgical drill's position and orientation relative to the patient phantom. Subsequently, the surgical drill is directed to the entry position, and the planned implantation paths are superimposed on the patient phantom using HoloLens 2 for visualization. Finally, the hybrid robot system performs the processed of drilling, expansion, and placement of ZIs under the guidance of the MR navigation system. RESULTS: Phantom experiments of ZI placement were conducted using 10 patient phantoms, with a total of 40 ZIs inserted. Out of these, 20 were manually implanted, and the remaining 20 were robotically implanted. Comparisons between the actual implanted ZI paths and the preoperatively planned ZI paths showed that our MR navigation-guided hybrid robotic system achieved a coronal deviation of 0.887 ± 0.213 mm, an apical deviation of 1.201 ± 0.318 mm, and an angular deviation of 3.468 ± 0.339° This demonstrates significantly better accuracy and stability than manual implantation. CONCLUSION: Our proposed hybrid robotic system enables automated ZI placement surgery guided by MR navigation, achieving greater accuracy and stability compared to manual operations in phantom experiments. Furthermore, this system is expected to apply to animal and cadaveric experiments, to get a good ready for clinical studies.

Pembrolizumab in patients from China with microsatellite instability-high/mismatch repair deficient tumors: KEYNOTE-158.

Aim: To evaluate pembrolizumab in patients of Chinese descent with microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) tumors enrolled in KEYNOTE-158 (Cohort L). Methods: Patients with MSI-H/dMMR advanced tumors received pembrolizumab 200 mg IV Q3W. Primary end point was overall response rate (ORR). Secondary end points were duration of response (DOR), progression-free survival (PFS) and overall survival (OS). Results: 24 patients were enrolled (20 were evaluable for efficacy). With median follow-up of 12.4 months, the ORR was 70%. DOR, PFS and OS were all not reached. A total of 19 (79%) patients had a treatment-related adverse event (AE; grade ≥3 in 4 [17%]), and 8 (33%) had an immune-mediated AE (grade ≥3 in (4 [17%]). Conclusion: Pembrolizumab provided meaningful and durable responses with manageable safety. These results are consistent with those reported for the global trial.

Causal effect of education on bone mineral density: A Mendelian randomization study.

Education level may have some association with the incidence of osteoporosis, but it is elusive if this association is causal. This two-sample Mendelian randomization analysis focused on the causal effect of education level on femoral neck bone mineral density (FN-BMD), forearm BMD, lumbar spine BMD, and heel BMD. Twelve single nucleotide polymorphisms were used as instrumental variables. The results suggested that high education level was associated with improved FN-BMD (beta-estimate: 0.406, 95% confidence interval: 0.061 to 0.751, standard error: 0.176, P-value = .021). There were null association between education and other sites of bone mineral density. Our results found the causal effect of high education level on improved FN-BMD, and improved educational attainment may be beneficial to prevent osteoporosis.

Analysis of Sex Hormones, Insulin Dosage, and Risk Factors Associated With Male Diabetic Patients.

The purpose of this study is to assess the influence of sex hormones and other indicators on risk factors for hypercoagulable states in male patients with type 2 diabetes mellitus. Ninety-two diabetic patients were divided into two groups based on testosterone levels: T1 group (testosterone <12 mmol/L) and T2 group (testosterone >12 mmol/L). Fifty-four non-diabetic patients were used as the control group. Sex hormone index, glucose, insulin, C-peptide, 24-h urinary free cortisol, thromboelastography, and insulin resistance index were measured by radioimmunoassay. Testosterone was lower in the diabetic men than in the control group (12.02 vs 14.77, p < .05), and was inversely related to blood coagulation status, blood glucose level, and cortisol level. Body mass index was positively correlated with estradiol and insulin resistance index. Testosterone was independently associated with the clotting process after controlling for age. Low testosterone is a risk factor for hypercoagulable state in diabetic men. Elevated estradiol and insulin resistance are influential factors for increased body mass index.

Microplastics derived from plastic mulch films and their carrier function effect on the environmental risk of pesticides.

Plastic film mulching can maintain soil water and heat conditions, promote plant growth and thus generate considerable economic benefits in agriculture. However, as they age, these plastics degrade and form microplastics (MPs). Additionally, pesticides are widely utilized to control organisms that harm plants, and they can ultimately enter and remain in the environment after use. Pesticides can also be sorbed by MPs, and the sorption kinetics and isotherms explain the three stages of pesticide sorption: rapid sorption, slow sorption and sorption equilibrium. In this process, hydrophobic and partition interactions, electrostatic interactions and valence bond interactions are the main sorption mechanisms. Additionally, small MPs, biodegradable MPs and aged conventional MPs often exhibit stronger pesticide sorption capacity. As environmental conditions change, especially in simulated biological media, pesticides can desorb from MPs. The utilization of pesticides by environmental microorganisms is the main factor controlling the degradation rate of pesticides in the presence of MPs. Pesticide sorption by MPs and size effects of MPs on pesticides are related to the internal exposure level of biological pesticides and changes in pesticide toxicity in the presence of MPs. Most studies have suggested that MPs exacerbate the toxicological effects of pesticides on sentinel species. Hence, the environmental risks of pesticides are altered by MPs and the carrier function of MPs. Based on this, research on the affinity between MPs and various pesticides should be systematically conducted. During agricultural production, pesticides should be cautiously selected and used plastic film to ensure human health and ecological security.

Partial order relation-based gene ontology embedding improves protein function prediction.

Protein annotation has long been a challenging task in computational biology. Gene Ontology (GO) has become one of the most popular frameworks to describe protein functions and their relationships. Prediction of a protein annotation with proper GO terms demands high-quality GO term representation learning, which aims to learn a low-dimensional dense vector representation with accompanying semantic meaning for each functional label, also known as embedding. However, existing GO term embedding methods, which mainly take into account ancestral co-occurrence information, have yet to capture the full topological information in the GO-directed acyclic graph (DAG). In this study, we propose a novel GO term representation learning method, PO2Vec, to utilize the partial order relationships to improve the GO term representations. Extensive evaluations show that PO2Vec achieves better outcomes than existing embedding methods in a variety of downstream biological tasks. Based on PO2Vec, we further developed a new protein function prediction method PO2GO, which demonstrates superior performance measured in multiple metrics and annotation specificity as well as few-shot prediction capability in the benchmarks. These results suggest that the high-quality representation of GO structure is critical for diverse biological tasks including computational protein annotation.