Exercise Alleviates CUS-Induced Depressive-Like Behaviors by Modulating Paracellular and Transcellular Permeability of the Blood-Brain Barrier in the Prefrontal Cortex.

BACKGROUND: Increased blood-brain barrier (BBB) permeability is implicated in the pathophysiology of major depressive disorder (MDD). While aerobic exercise has shown promise in mitigating MDD symptoms by potentially preserving BBB integrity, the detailed mechanisms remain unclear. This study explores these mechanisms to assess aerobic exercise's therapeutic potential for MDD. METHODS: Male C57BL/6J mice were used in this study to investigate the effects of aerobic exercise on CUS-induced BBB permeability and depressive-like behaviors. Chronic unpredictable stress (CUS)-induced MDD mouse models were divided into three groups: Control, CUS, and CUS+Exercise. We monitored body weight, blood S100ß levels, and cytokines via ELISA. Claudin-5 and Caveolin-1 (CAV-1) expressions in the medial prefrontal cortex were evaluated using Western blotting and immunofluorescence. BBB permeability was assessed using biocytin-TMR and Alb-Alexa 594 tracers. Transmission electron microscopy was used to observe ultrastructural changes in the BBB directly. Depression-related behaviors were tested through several behavioral assays. RESULTS: CUS significantly increased CAV-1 expression and Alb-Alexa 594 leakage, suggesting enhanced transcellular BBB permeability. Despite unchanged Claudin-5 levels, its tight junction ultrastructure was altered, leading to increased biocytin-TMR leakage. Aerobic exercise ameliorated these disruptions, reduced inflammatory cytokines, and improved behavioral outcomes in CUS mice. CONCLUSION: Disruptions in both paracellular and transcellular BBB pathways are pivotal in depression development. Aerobic exercise offers potential therapeutic benefits for MDD linked with BBB dysfunction by mitigating stress-induced structural and functional changes.

Unveiling correlations between aristolochic acids and liver cancer: spatiotemporal heterogeneity phenomenon.

Aristolochic acids are a class of naturally occurring compounds in Aristolochiaceae that have similar structural skeletons and chemical properties. Exposure to aristolochic acids is a risk factor for severe kidney disease and urinary system cancer. However, the carcinogenicity of aristolochic acids to the liver, which is the main site of aristolochic acid metabolism, is unclear. Although the characteristic fingerprint of aristolochic acid-induced mutations has been detected in the liver and aristolochic acids are known to be hepatotoxic, whether aristolochic acids can directly cause liver cancer is yet to be verified. This review summarizes the findings of long-term carcinogenicity studies of aristolochic acids in experimental animals. We propose that spatiotemporal heterogeneity in the carcinogenicity of these phytochemicals could explain why direct evidence of aristolochic acids causing liver cancer has never been found in adult individuals. We also summarized the reported approaches to mitigate aristolochic acid-induced hepatotoxicity to better address the associated global safety issue and provide directions and recommendations for future investigation.

Bilateral Proxy Federated Domain Generalization for Privacy-preserving Medical Image Diagnosis.

Contemporary domain generalization methods have demonstrated effectiveness in aiding the generalized diagnosis of medical images with multi-source data by joint optimization. However, the centralized training paradigm employed by these approaches becomes infeasible when data are non-shared across domains due to the high privacy of medical data. Despite attempts by existing federated domain generalization methods to address this issue, the simultaneous attainment of strict privacy protection and a satisfactory level of generalization ability on out-of-distribution data remains a persistent challenge. In this paper, to tackle this challenging problem, we propose a novel approach called the Bilateral Proxy Framework (BPF). The BPF leverages the client-side proxies to facilitate the strict privacy-preserving communications with the server and ensure smoother and more stable convergences of local models through mutual distillation. Meanwhile, the server-side proxy adopts a distance-based strategy and a parameter moving average scheme, which enhances the stability and robustness of the global model, particularly by averting abrupt parameter changes that could result in fluctuations or overfitting. Through these advancements, our framework strives to enhance the generalization capability of the global model, enabling more accurate and reliable medical image diagnosis in federated settings. The effectiveness of our method is demonstrated with superior performance over state-of-the-arts on both simulated and real-world distribution medical image diagnosis tasks.

Anatomic femoral tunnel and satisfactory clinical outcomes achieved with the modified transtibial technique in anterior cruciate ligament reconstruction: A systematic review and meta-analysis.

Background: Anatomic anterior cruciate ligament (ACL) reconstruction is considered the gold standard treatment for ACL injuries because it aims to restore the knee's normal anatomy and stability, while also protecting long-term knee health. Long-term clinical and radiological outcomes after ACL reconstruction using the modified TT technique are unclear. Objective: To assess the clinical and radiological outcomes following ACL reconstruction using modified transtibial (TT) techniques at a minimum 12-month follow-up. Design: A systematic review with meta-analysis. Methods: PubMed, EMBASE, Web of Science, the Cochrane Library, and MEDLINE databases were searched from the inception to December 1, 2022. PICO search strategy was used to identify studies applying modified TT techniques on patients with ACL reconstruction and a minimum follow-up of 12 months. Eligible studies were identified independently by two reviewers. We extracted data on patient demographics, surgical characteristics, patient reported outcomes including subjective evaluations and clinical outcomes. Radiological data including femoral and tibial tunnel position, femoral and tibial tunnel length, and femoral tunnel angle were also extracted. The tunnel position was evaluated using the quadrant method based on three-dimensional computed tomography (3D CT) images. The standardized mean difference (SMD) and 95 % confidence interval (CI) were calculated for clinical and radiological outcomes. Results: Sixteen studies involving 628 patients were finally included. The SMD of Lysholm (90.39; 95 % CI 83.41-97.38), IKDC (86.07; 95 % CI 79.84-92.31), and Tegner (6.15; 95 % CI 3.96-8.33) scores were considered satisfactory. The depth of the femoral tunnel showed a pooled SMD of 30.08 % (95 % CI 28.25-31.91 %), and the height showed a pooled SMD of 37.72 % (95 % CI 35.75-39.70 %). The pooled SMD for the femoral tunnel angle in the coronal plane was 48.27°(95 % CI 43.14-53.40°), and the pooled SMD for the femoral tunnel length was 33.98 mm (95 % CI 29.03-38.93 mm). Conclusions: This investigation has shown that modified TT technique can create an anatomic femoral tunnel and maintain optimal tunnel length and angulation. Most patients had satisfactory subjective outcomes and physical examinations after ACL reconstruction using modified TT technique. This information may assist in guiding expectations of clinicians and patients following ACL reconstruction with modified TT technique.

The application value of prenatal ultrasound in conjoined twins.

OBJECTIVE: To evaluate the application and effectiveness of prenatal ultrasound in diagnosing and managing conjoined twins. METHODS: A retrospective analysis was conducted on 20 cases of conjoined twins diagnosed at our hospital between January 2016 and December 2022. The types of conjoined twins, ultrasonographic characteristics, and associated anomalies were assessed. RESULTS: The gestational age at diagnosis ranged from 10 to 35 weeks, with an average of 14.21 ± 5.69 weeks. Thirteen cases were detected in the first trimester, five in the early second trimester, one at 23 + 2 weeks, and one at 35 weeks. Thoracopagus was the most common type (11 cases, 55%), followed by omphalopagus (4 cases, 20%), cephalopagus (4 cases, 20%), and parapagus dicephalus (1 case, 5%). In the first trimester, the most common abnormalities observed included increased nuchal translucency (NT), cystic hygroma, hydrops fetalis, and generalized edema. Major birth defects identified in conjoined twins were omphalocele (3 cases), congenital heart malformations (3 cases), neural tube defects (2 cases), urachal cyst (1 case), and umbilical cyst (1 case). Pregnancy was terminated in 18 cases, one case resulted in spontaneous abortion during the second trimester, and one case was delivered by cesarean section at 37 weeks, with successful separation and recovery. CONCLUSION: Prenatal ultrasound is the primary diagnostic tool for conjoined twins. It effectively assesses the extent of twin fusion, provides critical information for clinical decision-making, and aids in the management of obstetric care.

Plin4 exacerbates cadmium-decreased testosterone level via inducing ferroptosis in testicular Leydig cells.

Strong evidence indicates that environmental stressors are the risk factors for male testosterone deficiency (TD). However, the mechanisms of environmental stress-induced TD remain unclear. Based on our all-cause male reproductive cohort, we found that serum ferrous iron (Fe2⁺) levels were elevated in TD donors. Then, we explored the role and mechanism of ferroptosis in environmental stress-reduced testosterone levels through in vivo and in vitro models. Data demonstrated that ferroptosis and lipid droplet deposition were observed in environmental stress-exposed testicular Leydig cells. Pretreatment with ferrostatin-1 (Fer-1), a specific ferroptosis inhibitor, markedly mitigated environmental stress-reduced testosterone levels. Through screening of core genes involved in lipid droplets formation, it was found that environmental stress significantly increased the levels of perilipins 4 (PLIN4) protein and mRNA in testicular Leydig cells. Further experiments showed that Plin4 siRNA reversed environmental stress-induced lipid droplet deposition and ferroptosis in Leydig cells. Additionally, environmental stress increased the levels of METTL3, METTL14, and total RNA m6A in testicular Leydig cells. Mechanistically, S-adenosylhomocysteine, an inhibitor of METTL3 and METTL14 heterodimer activity, restored the abnormal levels of Plin4, Fe2⁺ and testosterone in environmental stress-treated Leydig cells. Collectively, these results suggest that Plin4 exacerbates environmental stress-decreased testosterone level via inducing ferroptosis in testicular Leydig cells.

Integrated metabolomics and transcriptomics analysis reveals the mechanism of Tangbi capsule for diabetic lower extremities arterial disease.

Objective: Tangbi capsule (TBC) is a traditional Chinese medicine prescription, which has the potential to improve the vascular insufficiency of lower extremities and limb numbness in diabetes. However, the potential mechanism remains unknown. This study aims to investigate the pharmacological effects and mechanism of TBC on rats with diabetic lower extremities arterial disease (LEAD). Methods: The mechanism of TBC on diabetic LEAD was investigated through metabolomics and transcriptomics analysis, and the main components of TBC were determined by mass spectrometry. The efficacy and mechanism of TBC on diabetic LEAD rats were investigated through in vitro experiments, histopathology, blood flow monitoring, western blot, and real-time polymerase chain reaction. Results: Mass spectrometry analysis identified 31 active chemical components in TBC including (2R)-2,3-Dihydroxypropanoic acid, catechin, citric acid, miquelianin, carminic acid, salicylic acid, formononetin, etc. In vitro analysis showed that TBC could reduce endothelial cell apoptosis and promote angiogenesis. Histopathological analysis showed that TBC led to an obvious improvement in diabetic LEAD as it improved fibrous tissue proliferation and reduced arterial wall thickening. In addition, TBC could significantly increase the expression levels of HIF-1α, eNOS, and VEGFA proteins and genes while reducing that of calpain-1 and TGF-ß, suggesting that TBC can repair vascular injury. Compared with the model group, there were 47 differentially expressed genes in the whole blood of TBC groups, with 25 genes upregulated and 22 downregulated. Eighty-seven altered metabolites were identified from the serum samples. Combining the changes in differentially expressed genes and metabolites, we found that TBC could regulate arginine biosynthesis, phenylalanine metabolism, pyrimidine metabolism, arachidonic acid metabolism, pyrimidine metabolism, arachidonic acid metabolism, nucleotide metabolism, vitamin B6 metabolism and other metabolic pathways related to angiogenesis, immune-inflammatory response, and cell growth to improve diabetic LEAD. Conclusion: TBC improved vascular endothelial injury, apoptosis, lipid accumulation, liver and kidney function, and restored blood flow in the lower extremities of diabetic LEAD rats. The mechanism of TBC in the treatment of diabetic LEAD may be related to the modulation of inflammatory immunity, lipid metabolism, and amino acid metabolism. This study presented preliminary evidence to guide the use of TBC as a therapy option for diabetic LEAD.

Development of an indirect ELISA for the immunoprotection evaluation of E2 antibodies against classical swine fever virus.

The Chinese government's reclassification of Classical Swine Fever (CSF) from a class Ⅰ to a class Ⅱ animal infectious disease, now also including CSF under the disease eradication program, reflects the significant progress made through extensive immunization with CSF vaccines. In light of this advancement, there is an imperative need for an expedient and accurate method to assess the levels of immunoprotection against classical swine fever virus (CSFV) in vaccinated pigs, a critical component in the campaign to eradicate the disease. This study develops an indirect enzyme-linked immunosorbent assay (iELISA) based on a highly glycosylated E2 protein stable expressed in CHO-K1 mammalian cells. Statistical analysis revealed strong positive correlations between the iELISA and VNT results (r = 0.9063, p < 0.0001) that were much greater than those between the IDEXX ELISA and VNT results (r = 0.8126, p < 0.0001). Taking the VNT data as the standard, the consistency of the iELISA (κ =0.880) was greater than that of the IDEXX ELISA (κ =0.699). In summary, the iELISA provides a more efficient and precise method for assessing CSFV immunity in pigs. Its reliable detection of immunoprotection levels against CSFV makes it an essential tool for optimizing CSF vaccination strategies. Consequently, its application can significantly support the ongoing efforts to eradicate CSF.

Bidirectional causality between the levels of blood lipids and endometriosis: a two-sample mendelian randomization study.

BACKGROUND: Observational studies have found a correlation between the levels of blood lipids and the development and progression of endometriosis (EM). However, the causality and direction of this correlation is unclear. This study aimed to examine the bidirectional connection between lipid profiles and the risk of EM using publicly available genome-wide association study (GWAS) summary statistics. METHODS: Eligible exposure variables such as levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were selected using a two-sample Mendelian randomization (MR) analysis method following a series of quality control procedures. Data on EM were obtained from the publicly available Finnish database of European patients. Inverse variance weighted (IVW), MR Egger, weighted median, and weighted mode methods were used to analyze the causal relationship between lipid exposure and EM, exclude confounders, perform sensitivity analyses, and assess the stability of the results. Reverse MR analyses were performed with EM as exposure and lipid results as study outcomes. RESULTS: IVW analysis results identified HDL as a protective factor for EM, while TG was shown to be a risk factor for EM. Subgroup analyses based on the site of the EM lesion identified HDL as a protective factor for EM of the uterus, while TG was identified a risk factor for the EM of the fallopian tube, ovary, and pelvic peritoneum. Reverse analysis did not reveal any effect of EM on the levels of lipids. CONCLUSION: Blood lipids, such as HDL and TG, may play an important role in the development and progression of EM. However, EM does not lead to dyslipidemia.

Household Environments and Cognitive Decline Among Middle-Aged and Older Adults in China: Exploring Gender, Age, and Residential Variations.

This study examined the relationship between household environments and trajectories of cognitive function among middle-aged and older adults in China and its urban/rural, gender, and age variations. We estimated multi-level linear growth curve models using a representative sample of 16,111 respondents aged 45 years and over from the China Health and Retirement Longitudinal Study (2011-2018). Older people who lived with a spouse, but not with children, and those with higher living expenditures, better housing quality, and indoor clean fuels for cooking had a slower cognitive decline. Living arrangement more strongly predicted men's cognitive decline, while living expenditure, solid fuel use, and housing quality significantly predicted only women's cognitive decline. Only for older adults and rural residents, those living alone had significantly faster cognitive decline than those living with a spouse only. These findings underscore the importance of improving the living conditions of older adults to help alleviate their cognitive decline.

Optimal tibial tunnel angulation for anatomical anterior cruciate ligament reconstruction using transtibial technique.

Numerous studies have suggested that the primary cause of failure in transtibial anterior cruciate ligament reconstruction (ACLR) is often attributed to non-anatomical placement of the bone tunnels, typically resulting from improper tibial guidance. We aimed to establish the optimal tibial tunnel angle for anatomical ACLR by adapting the transtibial (TT) technique. Additionally, we aimed to assess graft bending angle (GBA) and length changes during in vivo dynamic flexion of the knee. Twenty knee joints underwent a CT scan and dual fluoroscopic imaging system (DFIS) to reproduce relative knee position during dynamic flexion. For the single-legged lunge, subjects began in a natural standing position and flexed the right knee beyond 90° When performing the lunge task, the subject supported the body weight on the right leg, while the left leg was used to keep the balance. The tibial and femoral tunnels were established on each knee using a modified TT technique for single-bundle ACLR. The tibial tunnel angulation to the tibial axis and the sagittal plane were measured. Considering that ACL injuries tend to occur at low knee flexion angles, GBA and graft length were measured between 0° and 90° of flexion in this study. The tibial tunnel angulated the sagittal plane at 42.8° ± 3.4°, and angulated the tibial axis at 45.3° ± 5.1° The GBA was 0° at 90° flexion of the knee and increased substantially to 76.4 ± 5.5° at 0° flexion. The GBA significantly increased with the knee extending from 90° to 0° (p < 0.001). The ACL length was 30.2mm±3.0 mm at 0° flexion and decreased to 27.5mm ± 2.8 mm at 90° flexion (p = 0.072). To achieve anatomic single-bundle ACLR, the optimal tibial tunnel should be angulated at approximately 43° to the sagittal plane and approximately 45° to the tibial axis using the modified TT technique. What's more, anatomical TT ACLR resulted in comparable GBA and a relatively constant ACL length from 0° to 90° of flexion. These findings provide theoretical support for the clinical application and the promotion of the current modified TT technique with the assistance of a robot to achieve anatomical ACLR.

The gut microbial composition in polycystic ovary syndrome with hyperandrogenemia and its association with steroid hormones.

Background: Polycystic ovary syndrome (PCOS) is characterized by excess androgens, ovulatory dysfunction, and polycystic ovaries. The mechanisms underlying ovulatory and metabolic disorders in PCOS remain elusive, hampering therapeutic development. Enhanced metabolic health correlates with increased microbiota gene content and microbial diversity. We aimed to explore the impact of gut microbiota and serum steroids on PCOS regulation associated with androgen excess. Methods: The fecal samples of patients with hyperandrogenic PCOS (n = 14) and control group with PCOS (n = 14) were analyzed by 16S rRNA gene sequencing. The peripheral venous blood of all subjects was collected to detect serum hormones. The association between gut microbiota and serum hormones was analyzed with the R language. Results: Our findings reveal that the hyperandrogenic PCOS group exhibits lower richness and diversity of gut microbiota compared to the control group. Characteristic genera in PCOS patients with hyperandrogenism include Bifidobacterium, Enterobacteriaceae_unclassified, Streptococcus, Saccharimonadaceae, Enterococcus, and Eubacterium_nodatum_group. Five hormones, including 5ß-androsterone, deoxycorticosterone, corticosterone, 11-dehydrocorticosterone, and cortexolone, emerge as potential serum biomarkers for identifying patients with hyperandrogenic-PCOS (HA-PCOS). Furthermore, a lower vitamin D3 level may act as a susceptibility factor, suggesting that vitamin D3 supplementation could serve as a potential intervention for PCOS with hyperandrogenism. Conclusion: Specific fecal microbiota and serum steroids may be used as characteristic markers for clinical diagnosis of hyperandrogenic-PCOS. This research enhances our understanding of the intricate interplay among hormones, gut microbiota, and hyperandrogenemia in patients with PCOS.

In vivo cervical vertebrae kinematic studies based on dual fluoroscopic imaging system measurement: A narrative review.

Understanding the motion characteristics of cervical spine through biomechanical analysis aids in the identification of abnormal joint movements. This knowledge is essential for the prevention, diagnosis, and treatment of related disorders. However, the anatomical structure of the cervical spine is complex, and traditional medical imaging techniques have certain limitations. Capturing the movement characteristics of various parts of the cervical spine in vivo during motion is challenging. The dual fluoroscopic imaging system (DFIS) is able to quantify the motion and motion patterns of individual segments. In recent years, DFIS has achieved accurate non-invasive measurements of dynamic joint movements in humans. This review assesses the research findings of DFIS about the cervical spine in healthy and pathological individuals. Relevant study search was conducted up to October 2023 in Web of Science, PubMed, and EBSCO databases. After the search, a total of 30 studies were ultimately included. Among them, 13 studies focused on healthy cervical spines, while 17 studies focused on pathological cervical spines. These studies mainly centered on exploring the vertebral bodies and associated structures of the cervical spine, including intervertebral discs, intervertebral foramina, and zygapophyseal joints. Further research could utilize DFIS to investigate cervical spine motion in different populations and under pathological conditions.

Social Determinants of Health and College Food Insecurity.

In recent years, many students have faced economic hardship and experienced food insecurity, even as universities strive to create more equitable pathways to college. There is a need for a more holistic perspective that addresses the complexity of food insecurity amongst college students. To this end, we examined the relationship between the social determinants of health, including college food insecurity (CoFI) and childhood food insecurity (ChFI), and their relationship with well-being measures. The study sample was a convenience sample that included 372 students at a public university who responded to an online survey in fall 2021. Students were asked to report their food security status in the previous 30 days. We used the following analytical strategies: chi-square tests to determine differences between food secure (FS) and food insecure (FI) students; binary logistic regression of CoFI on student demographics and ChFI; and ordinal or binary logistic regression for well-being measures. Black students, off-campus students, first-generation students, in-state students, and humanities/behavioral/social/health sciences majors were more likely to report CoFI. FI students were more likely to have experienced ChFI and to have lower scores on all well-being measures. ChFI was associated with four well-being measures and its effects were mediated by CoFI. College student health initiatives would benefit from accounting for SDOH, including ChFI experiences and its subsequent cumulative disadvantages experienced during college.

m6A-methylated Lonp1 drives mitochondrial proteostasis stress to induce testicular pyroptosis upon environmental cadmium exposure.

Cadmium (Cd) is a widely distributed typical environmental pollutant and one of the most toxic heavy metals. It is well-known that environmental Cd causes testicular damage by inducing classic types of cell death such as cell apoptosis and necrosis. However, as a new type of cell death, the role and mechanism of pyroptosis in Cd-induced testicular injury remain unclear. In the current study, we used environmental Cd to generate a murine model with testicular injury and AIM2-dependent pyroptosis. Based on the model, we found that increased cytoplasmic mitochondrial DNA (mtDNA), activated mitochondrial proteostasis stress occurred in Cd-exposed testes. We used ethidium bromide to generate mtDNA-deficient testicular germ cells and further confirmed that increased cytoplasmic mtDNA promoted AIM2-dependent pyroptosis in Cd-exposed cells. Uracil-DNA glycosylase UNG1 overexpression indicated that environmental Cd blocked UNG-dependent repairment of damaged mtDNA to drive the process in which mtDNA releases to cytoplasm in the cells. Interestingly, we found that environmental Cd activated mitochondrial proteostasis stress by up-regulating protein expression of LONP1 in testes. Testicular specific LONP1-knockdown significantly reversed Cd-induced UNG1 protein degradation and AIM2-dependent pyroptosis in mouse testes. In addition, environmental Cd significantly enhanced the m6A modification of Lonp1 mRNA and its stability in testicular germ cells. Knockdown of IGF2BP1, a reader of m6A modification, reversed Cd-induced upregulation of LONP1 protein expression and pyroptosis activation in testicular germ cells. Collectively, environmental Cd induces m6A modification of Lonp1 mRNA to activate mitochondrial proteostasis stress, increase cytoplasmic mtDNA content, and trigger AIM2-dependent pyroptosis in mouse testes. These findings suggest that mitochondrial proteostasis stress is a potential target for the prevention of testicular injury.

Household Environments and Functional Decline Among Middle-Aged and Older Adults in China: Variations by Gender, Age, and Residence.

This study examined the associations between household social, economic, and physical environments and the trajectory of functional limitations over time among middle-aged and older adults in China, and how this relationship differs by gender, age, and residence. Linear growth curve models were applied to a sample of 13,564 respondents aged 45 years and older from four waves of the China Health and Retirement Longitudinal Study (CHARLS 2011-2018). Living alone, particularly for rural, female, and older respondents, was associated with a faster functional decline when compared to living with a spouse and without children. Improved housing quality was associated with a slower functional decline. Living with young descendants and without adult children for urban residents and a lower expenditure per capita for younger respondents were associated with a faster functional decline. These findings suggest that policies aimed at enhancing living conditions have the potential to improve physical functioning of older adults.

Effects of added trunk load on the in vivo kinematics of talocrural and subtalar joints during landing.

BACKGROUND: Landing from heights is a common movement for active-duty military personnel during training. And the additional load they carry while performing these tasks can affect the kinetics and ankle kinematic of the landing. Traditional motion capture techniques are limited in accurately capturing the in vivo kinematics of the talus. This study aims to investigate the effect of additional trunk load on the kinematics of the talocrural and subtalar joints during landing, using a dual fluoroscopic imaging system (DFIS). METHODS: Fourteen healthy male participants were recruited. Magnetic resonance imaging was performed on the right ankle of each participant to create three-dimensional (3D) models of the talus, tibia, and calcaneus. High-speed DFIS was used to capture the images of participants performing single-leg landing jumps from a height of 40 cm. A weighted vest was used to apply additional load, with a weight of 16 kg. Fluoroscopic images were acquired with or without additional loading condition. Kinematic data were obtained by importing the DFIS data and the 3D models in virtual environment software for 2D-3D registration. The kinematics and kinetics were compared between with or without additional loading conditions. RESULTS: During added trunk loading condition, the medial-lateral translation range of motion (ROM) at the talocrural joint significantly increased (p < 0.05). The subtalar joint showed more extension at 44-56 ms (p < 0.05) after contact. The subtalar joint was more eversion at 40-48 ms (p < 0.05) after contact under the added trunk load condition. The peak vertical ground reaction force (vGRF) significantly increased (p < 0.05). CONCLUSIONS: With the added trunk load, there is a significant increase in peak vGRF during landing. The medial-lateral translation ROM of the talocrural joint increases. And the kinematics of the subtalar joint are affected. The observed biomechanical changes may be associated with the high incidence of stress fractures in training with added load.

[Prediction of CRISPR/Cas9 off-target activity using multi-scale convolutional neural network].

Clustered regularly interspaced short palindromic repeat/CRISPR-associated protein 9 (CRISPR/Cas9) is a new generation of gene editing technology, which relies on single guide RNA to identify specific gene sites and guide Cas9 nuclease to edit specific location in the genome. However, the off-target effect of this technology hampers its development. In recent years, several deep learning models have been developed for predicting the CRISPR/Cas9 off-target activity, which contributes to more efficient and safe gene editing and gene therapy. However, the prediction accuracy remains to be improved. In this paper, we proposed a multi-scale convolutional neural network-based method, designated as CnnCRISPR, for CRISPR/Cas9 off-target prediction. First, we used one-hot encoding method to encode the sgRNA-DNA sequence pair, followed by a bitwise or operation on the two binary matrices. Second, the encoded sequence was fed into the Inception-based network for training and evaluating. Third, the well-trained model was applied to evaluate the off-target situation of the sgRNA-DNA sequence pair. Experiments on public datasets showed CnnCRISPR outperforms existing deep learning-based methods, which provides an effective and feasible method for addressing the off-target problems.

Ultrasound manifestations and clinical analysis of 50 cases of heterotopic pregnancy.

OBJECTIVE: To investigate the value of ultrasonography in the diagnosis of heterotopic pregnancy and the follow-up. METHODS: A retrospective analysis of 50 cases of clinically diagnosed heterotopic pregnancy in our hospital was performed, the clinical characteristics and ultrasonographic manifestations of the patients were summarized, the reasons for initial ultrasound missed diagnosis and misdiagnosis were analyzed, and the pregnancy outcomes were followed up. RESULTS: Among the 50 cases, the initial ultrasound diagnoses of intrauterine pregnancy were all gestational sac type, 32 cases of ectopic pregnancy were located in the fallopian tube, and 10 cases were located in the uterine horn, 1 case at cervix, and 1 case at caesarean section scar. Forty-one cases were consistent with surgery and/or pathology, representing initial ultrasound diagnosis coincidence rate of about 82%. Six cases were missed in the initial ultrasound examination (12%), and three cases were misdiagnosed (6%). The maximum diameter of the intrauterine gestational sac was 9-48 mm, the average was about 24.90 ± 9.56 mm, the maximum diameter of the ectopic pregnancy gestational sac or mass was 11-63 mm, and the average was about 31.45 ± 13.82 mm (p < 0.05). Intrauterine pregnancy outcomes were followed up, 45 patients with complete data and 5 patients were lost to follow-up. The follow-up rate was about 90%. CONCLUSION: Combining the patient's medical history and clinical characteristics can reduce missed diagnosis and misdiagnosis of heterotopic pregnancy. Ultrasonography has important value in the assessment of intrauterine pregnancy growth and development, and the integrity of maternal uterus.

Environmental cadmium inhibits testicular testosterone synthesis via Parkin-dependent MFN1 degradation.

Low testosterone (T) levels are associated with many common diseases, such as obesity, male infertility, depression, and cardiovascular disease. It is well known that environmental cadmium (Cd) exposure can induce T decline, but the exact mechanism remains unclear. We established a murine model in which Cd exposure induced testicular T decline. Based on the model, we found Cd caused mitochondrial fusion disorder and Parkin mitochondrial translocation in mouse testes. MFN1 overexpression confirmed that MFN1-dependent mitochondrial fusion disorder mediated the Cd-induced T synthesis suppression in Leydig cells. Further data confirmed Cd induced the decrease of MFN1 protein by increasing ubiquitin degradation. Testicular specific Parkin knockdown confirmed Cd induced the ubiquitin-dependent degradation of MFN1 protein through promoting Parkin mitochondrial translocation in mouse testes. Expectedly, testicular specific Parkin knockdown also mitigated testicular T decline. Mito-TEMPO, a targeted inhibitor for mitochondrial reactive oxygen species (mtROS), alleviated Cd-caused Parkin mitochondrial translocation and mitochondrial fusion disorder. As above, Parkin mitochondrial translocation induced mitochondrial fusion disorder and the following T synthesis repression in Cd-exposed Leydig cells. Collectively, our study elucidates a novel mechanism through which Cd induces T decline and provides a new treatment strategy for patients with androgen disorders.