pH Homeodynamics and Male Fertility: A Coordinated Regulation of Acid-Based Balance during Sperm Journey to Fertilization.

pH homeostasis is crucial for spermatogenesis, sperm maturation, sperm physiological function, and fertilization in mammals. HCO3- and H+ are the most significant factors involved in regulating pH homeostasis in the male reproductive system. Multiple pH-regulating transporters and ion channels localize in the testis, epididymis, and spermatozoa, such as HCO3- transporters (solute carrier family 4 and solute carrier family 26 transporters), carbonic anhydrases, and H+-transport channels and enzymes (e.g., Na+-H+ exchangers, monocarboxylate transporters, H+-ATPases, and voltage-gated proton channels). Hormone-mediated signals impose an influence on the production of some HCO3- or H+ transporters, such as NBCe1, SLC4A2, MCT4, etc. Additionally, ion channels including sperm-specific cationic channels for Ca2+ (CatSper) and K+ (SLO3) are directly or indirectly regulated by pH, exerting specific actions on spermatozoa. The slightly alkaline testicular pH is conducive to spermatogenesis, whereas the epididymis's low HCO3- concentration and acidic lumen are favorable for sperm maturation and storage. Spermatozoa pH increases substantially after being fused with seminal fluid to enhance motility. In the female reproductive tract, sperm are subjected to increasing concentrations of HCO3- in the uterine and fallopian tube, causing a rise in the intracellular pH (pHi) of spermatozoa, leading to hyperpolarization of sperm plasma membranes, capacitation, hyperactivation, acrosome reaction, and ultimately fertilization. The physiological regulation initiated by SLC26A3, SLC26A8, NHA1, sNHE, and CFTR localized in sperm is proven for certain to be involved in male fertility. This review intends to present the key factors and characteristics of pHi regulation in the testes, efferent duct, epididymis, seminal fluid, and female reproductive tract, as well as the associated mechanisms during the sperm journey to fertilization, proposing insights into outstanding subjects and future research trends.

Bionic design of thin-walled bilinear tubes with excellent crashworthiness inspired by glass sponge structures.

In order to enhance energy absorption, this study draws inspiration from the diagonal bilinear robust square lattice structure found in deep-sea glass sponges, proposing a design for thin-walled structures with superior folding capabilities and high strength-to-weight ratio. Firstly, the crashworthiness of bionic glass sponge tube (BGSTO) is compared with that of equal-wall-thickness equal-mass four-X tube through both experiments and simulations, and it is obtained that the specific energy absorption of BGSTO is increased by 78.64%. And the crashworthiness of BGSTO is also most significant compared to that of multicellular tubes with the similar number of crystalline cells. Additionally, we found that the double-line spacing of the glass sponge can be freely adjusted without changing the material amount. Therefore, based on BGSTO, we designed two other double-line structures, BGSTA and BGSTB. Then with equal wall thickness and mass as a prerequisite, this study proceeds to design and compare the energy absorption properties of three bilinear thin-walled tubes in both axial and lateral cases. The deformation modes and crashworthiness of the three types of tubes with variable bilinear spacing (ßO/A/B) are comparatively analysed. The improved complex proportional assessment (COPRAS) synthesis decision is used to obtain that BGSTO exhibits superior crashworthiness over the remaining two kinds of tubes. Finally, a surrogate model is established to perform multi-objective optimization on the optimal bilinear configuration BGSTO selected by the COPRAS method.

Identification of RACK1 as a novel regulator of non-structural protein 4 of chikungunya virus.

Chikungunya virus (CHIKV) is a neglected arthropod-borne and anthropogenic alphavirus. Over the past two decades, the CHIKV distribution has undergone significant changes worldwide, from the original tropics and subtropics regions to temperate regions, which has attracted global attention. However, the interactions between CHIKV and its host remain insufficiently understood, which dampens the need for the development of an anti-CHIKV strategy. In this study, on the basis of the optimal overexpression of non-structural protein 4 (nsP4), we explore host interactions of CHIKV nsP4 using mass spectrometry-based protein-protein interaction approaches. The results reveal that some cellular proteins that interact with nsP4 are enriched in the ubiquitin-proteasome pathway. Specifically, the scaffold protein receptor for activated C kinase 1 (RACK1) is identified as a novel host interactor and regulator of CHIKV nsP4. The inhibition of the interaction between RACK1 and nsP4 by harringtonolide results in the reduction of nsP4, which is caused by the promotion of degradation but not the inhibition of nsP4 translation. Furthermore, the decrease in nsP4 triggered by the RACK1 inhibitor can be reversed by the proteasome inhibitor MG132, suggesting that RACK1 can protect nsP4 from degradation through the ubiquitin-proteasome pathway. This study reveals a novel mechanism by which the host factor RACK1 regulates CHIKV nsP4, which could be a potential target for developing drugs against CHIKV.

Study on the factors affecting the mechanical properties of antler under quasi-static compression.

In the natural environment, antlers have a significant mechanical structure that protects the deer head from injury. In this paper, the mechanical properties of antlers were evaluated through quasi-static compression tests and microstructural observation of samples from antlers, and the relationship between the sampling position, load direction, and microstructure and their mechanical properties were investigated. Compression experiments confirmed that the tines had the strongest mechanical properties, followed by the main beams and finally the brow tines. The mechanical properties of the test specimens subjected to axial compression were higher than those of lateral compression. The axial load test of the longitudinal sample of the tine of the antler has the best mechanical properties. Its specific energy absorption is 51.33 J/g, the peak crushing force is 1.26 kN, and the mean crushing force is 1.47 kN. There are many tubular structures in the transverse sections of antlers, and the distribution of fibers in the vertical direction is laminar with alternating rows forming a helical structure. Tubular structures were found to be prevalent in some of the better biomechanical structures by comparison. Numerical modeling simulations to describe the effect of tubular structures on the mechanical properties of antlers. The simulation results show that the increase in the size of the tubular structure improves its energy absorption within the variation of a 20% increase in the size of the long and short axis. These findings provide a theoretical and experimental basis for the design of energy-absorbing structures. RESEARCH HIGHLIGHTS: In this paper, transverse and longitudinal samples were taken from the main beam, tine, and brow tine of antlers, and axial and lateral compression were carried out, respectively. In this paper, quasi-static compression experiments were carried out on antler samples to study the effects of sampling position, loading direction, and microstructure on antler mechanical properties. By means of microstructure observation and numerical modeling, it is determined that the size of the antler Havel tube has an effect on its mechanical properties.

Nontargeted Analysis of Coumarins in Source Water and Their Formation of Chlorinated Coumarins as DBPs in Drinking Water.

Coumarin was detected as one of the most abundant compounds by nontargeted analysis of natural product components in actual water samples prior to disinfection. More importantly, prechlorination of humic acid generated 3-hydroxycoumarin and monohydroxy-monomethyl-substituted coumarin with a total yield of ≤10.1%, which suggested the humic substance in raw water is an important source of coumarins. 7-Hydroxycoumarin, 6-hydroxy-4-methylcoumarin, 6,7-dihydroxycoumarin, and 7-methoxy-4-methylcoumarin were identified in raw water by high-performance liquid chromatography-tandem high-resolution mass spectrometry because only some coumarin standards were commercially available. Their chlorination generated monochlorinated and polychlorinated coumarins, and their structures were confirmed by the synthesized standards. These products could form at various dosages of chlorine and pH levels, and some with a concentration of 600 ng/L can be stable in tap water for days. 3,6,8-Trichloro-7-hydroxycoumarin, 3-chloro-7-methoxy-4-methylcoumarin, and 3,6-dichloro-7-methoxy-4-methylcoumarin were first identified in finished water with concentrations of 0.0670, 78.1, and 14.7 ng/L, respectively, but not in source water, suggesting that they are new DBPs formed during disinfection. The cytotoxicity of 3-chloro-7-methoxy-4-methylcoumarin in CHO-K1 cells was comparable to those of 2,6-dibromo-1,4-benzoquinone and 2,6-dichloro-1,4-benzoquinone in TIC-Tox analyses, suggesting that further investigation of their occurrence and control in drinking water systems is warranted.

Biomimetic lizard robot for adapting to Martian surface terrain.

The exploration of the planet Mars still is a top priority in planetary science. The Mars surface is extensively covered with soil-like material. Current wheeled rovers on Mars have been occasionally experiencing immobilization instances in unexpectedly weak terrains. The development of Mars rovers adaptable to these terrains is instrumental in improving exploration efficiency. Inspired by locomotion of the desert lizard, this paper illustrates a biomimetic quadruped robot with structures of flexible active spine and toes. By accounting for spine lateral flexion and its coordination with four leg movements, three gaits of tripod, trot and turning are designed. The motions corresponding to the three gaits are conceptually and numerically analyzed. On the granular terrains analog to Martian surface, the gasping forces by the active toes are estimated. Then traversing tests for the robot to move on Martian soil surface analog with the three gaits were investigated. Moreover, the traversing characteristics for Martian rocky and slope surface analog are analyzed. Results show that the robot can traverse Martian soil surface analog with maximum forward speed 28.13 m s-1turning speed 1.94° s-1and obstacle height 74.85 mm. The maximum angle for climbing Martian soil slope analog is 28°, corresponding slippery rate 76.8%. It is predicted that this robot can adapt to Martian granular rough terrain with gentle slopes.

Comparative Analysis of Macro/Microstructures and Constituents of Sorghum and Reed Straw.

Node-containing straws exhibit superior mechanical properties compared to node-free straw plants, particularly in terms of shear resistance and compression resistance. We explore the relationship between the structure and mechanical properties of straw materials, providing deeper insights for the field of biomechanics. In this study, we focused on two node-containing straw plants, namely sorghum and reed. The main characteristics of sorghum and reed stalks were compared using macroscopic observation, stereomicroscopy, scanning electron microscopy, infrared spectroscopy, and EDS analysis. This study revealed numerous similarities and differences in the macro- and microstructures as well as the elemental composition of sorghum and reed stalks. The functional groups in sorghum and reed stalks were largely similar, with the primary elements being C and O. Distinguishing features included a higher tapering and a slightly larger reduction in wall thickness in sorghum stalks compared to reed stalks. The cross-section of sorghum stalks was filled with pith structures, while reed stalks exhibited a hollow structure. The vascular bundles in sorghum typically showed a paired arrangement, whereas those in reeds were arranged in odd numbers. Furthermore, sorghum straws contained more Cl and no Br, while the parenchyma of reed straws contained higher Br. The C and O proportions of sorghum straws and reed straws are 50-53% (50-51%) and 45-46% (48-49%), respectively. These variations in elemental composition are believed to be correlated with the mechanical properties of the materials. By conducting a detailed study of the micro/macrostructures and material composition of sorghum and reed straw, this paper provides valuable insights for the field of biomechanics.

3D-CT measurements of facial symmetry in severe CFM patients: A comparative study between mandibular ascending ramus distraction osteogenesis and bone grafting.

This study aims to compare the effects of mandibular distraction osteogenesis (MDO) and bone grafting on the facial symmetry of children with Pruzansky-Kaban type IIB and III craniofacial microsomia (CFM). Medical records and three-dimensional computed tomography (3D-CT) data of CFM patients who had primarily undergone MDO and bone grafting were collected. A retrospective analysis of pre-and post-operative 3D imaging data was conducted to compare the improvement rate in facial symmetry between the two groups based on occlusal cant, affected/unaffected ramus height ratio and chin point deviation. The data were tested for normality using the Shapiro-Wilk test. When the data followed a normal distribution, a paired sample t-test was employed for the comparison between preoperative and postoperative data. When the data did not follow a normal distribution, the Wilcoxon signed-rank test for paired samples was used for preoperative and postoperative comparison. The study included 18 children with type IIB and III CFM, 11 in the MDO group and 7 in the bone grafting group. In the MDO group, postoperative Gn-FH and Gn-Cor distances increased significantly, whereas the postoperative Gn-Mid distance decreased significantly. Occlusal cant decreased significantly and ramus height affected/unaffected ratio increased significantly after MDO. In the bone graft group, there was no statistically significant difference in the postoperative ratios of chin deviation, occlusal cant, and ramus height affected/unaffected compared to the preoperative values. Compared to bone grafting, MDO can significantly enhance ramus height ratio, level occlusal plane, and centralize the chin point among patients with CFM. Furthermore, MDO achieves superior enhancements in facial symmetry.

Biomimetic Study of a Honeycomb Energy Absorption Structure Based on Straw Micro-Porous Structure.

In this paper, sorghum and reed, which possess light stem structures in nature, were selected as biomimetic prototypes. Based on their mechanical stability characteristics-the porous structure at the node feature and the porous feature in the outer skin- biomimetic optimization design, simulation, and experimental research on both the traditional hexagonal structure and a hexagonal honeycomb structure were carried out. According to the two types of straw microcell and chamber structure characteristics, as well as the cellular energy absorption structure for the bionic optimization design, 22 honeycomb structures in 6 categories were considered, including a corrugated cell wall bionic design, a modular cell design, a reinforcement plate structure, and a self-similar structure, as well as a porous cell wall structure and gradient structures of variable wall thickness. Among them, HTPC-3 (a combined honeycomb structure), HSHT (a self-similar honeycomb structure), and HBCT-257 (a radial gradient variable wall thickness honeycomb structure) had the best performance: their energy absorption was 41.06%, 17.84%, and 83.59% higher than that of HHT (the traditional hexagonal honeycomb decoupling unit), respectively. Compared with HHT (a traditional hexagon honeycomb decoupling unit), the specific energy absorption was increased by 39.98%, 17.24%, and 26.61%, respectively. Verification test analysis revealed that the combined honeycomb structure performed the best and that its specific energy absorption was 22.82% higher than that of the traditional hexagonal structure.

Identification of autophagy-related genes in diabetic foot ulcer based on bioinformatic analysis.

Diabetic foot ulcer (DFU) complications involve autophagy dysregulation. This study aimed to identify autophagy-related bioindicators in DFU. Differentially expressed genes (DEGs) between DFU and healthy samples were analysed from the Gene Expression Omnibus (GEO) datasets, GSE7014 and GSE29221. The roles of autophagy-related DEGs were investigated using protein-protein interaction (PPI) networks, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, Gene Ontology (GO) enrichment, and Gene Set Enrichment Analysis (GSEA). Immune cell infiltration's correlation with these DEGs was also assessed. From the Human Autophagy Database (HADB), 232 autophagy-related genes (ARGs) were identified, with an intersection of 17 key DEGs between GSE7014 and GSE29221. These genes are involved in pathways like autophagy-animal, NOD-like receptor signalling, and apoptosis. In the protein network, epidermal growth factor receptor (EGFR) and phosphatase and tensin homologue (PTEN) showed significant interactions with ARGs. Survival analysis indicated the prognostic importance of calpain 2 (CAPN2), integrin subunit beta 1 (ITGB1), and vesicle-associated membrane protein 3 (VAMP3). Lower immune scores were observed in the type 2 diabetes mellitus (DM2) group than in controls. Autophagy and ARGs significantly influence DFU pathophysiology.

Mesoscopic analysis of drag reduction performance of bionic furrow opener based on the discrete element method.

In order to study the dynamic interface mechanical behavior between soil and agricultural machinery and reveal the causes of tillage resistance, three kinds of bionic furrow opener were designed according to the characteristics of earthworm head surface curve, using the discrete element method to simulate and analyze the process of the furrow openers. The results showed that the order of ditching resistance from large to small is traditional opener, bionic corrugated opener, bionic ridgeline opener, bionic composite opener. With the same ditching speed, the drag reduction effect of the three bionic openers increases with the increase of the ditching depth. During the process of increasing the depth from 30 mm to 60 mm and 90 mm, the ditching resistance of the traditional opener increased from 11.56 N to 28.32 N and 48.61 N as well as the maximum drag reduction ratio increased from 5.58% to 7.20% and 8.93% for the bionic composite opener. With the same ditching depth, the bionic composite opener reached the highest drag reduction rate of all bionic openers when the speed is 100 mm/s, the value is 9.08%. The width of the ditch of the three bionic openers is smaller than that of the traditional opener. Bionic corrugated opener can improve the ditch height and reduce the ditch width,the corrugated structure creates a gap between the surface of the core and the particles, reducing the number of contact and contact area of the particles. The number of contact particles of the three bionic openers is smaller than that of the traditional opener. The bionic composite opener has the smallest force field and the soil disturbance caused by the core share surface is small, the soil is evenly distributed along the core surface. The discrete element simulation shows that the bionic opener can effectively reduce the ditching resistance and improve the quality of ditching, which provides a theoretical basis for subsequent research and optimization.

Unveiling the Potential of Bacillus safensis Y246 for Enhanced Suppression of Rhizoctonia solani.

Rhizoctonia solani is a significant pathogen affecting various crops, including tobacco. In this study, a bacterial strain, namely Y246, was isolated from the soil of healthy plants and exhibited high antifungal activity. Based on morphological identification and DNA sequencing, this bacterial strain was identified as Bacillus safensis. The aim of this investigation was to explore the antifungal potential of strain Y246, to test the antifungal stability of Y246 by adjusting different cultivation conditions, and to utilize gas chromatography-mass spectrometry (GC-MS) to predict the volatile compounds related to antifungal activity in Y246. In vitro assays demonstrated that strain Y246 exhibited a high fungal inhibition rate of 76.3%. The fermentation broth and suspension of strain Y246 inhibited the mycelial growth of R. solani by 66.59% and 63.75%, respectively. Interestingly, treatment with volatile compounds derived from the fermentation broth of strain Y246 resulted in abnormal mycelial growth of R. solani. Scanning electron microscopy analysis revealed bent and deformed mycelium structures with a rough surface. Furthermore, the stability of antifungal activity of the fermentation broth of strain Y246 was assessed. Changes in temperature, pH value, and UV irradiation time had minimal impact on the antifungal activity, indicating the stability of the antifungal activity of strain Y246. A GC-MS analysis of the volatile organic compounds (VOCs) produced by strain Y246 identified a total of 34 compounds with inhibitory effects against different fungi. Notably, the strain demonstrated broad-spectrum activity, exhibiting varying degrees of inhibition against seven pathogens (Alternaria alternata, Phomopsis. sp., Gloeosporium musarum, Dwiroopa punicae, Colletotrichum karstii, Botryosphaeria auasmontanum, and Botrytis cinerea). In our extensive experiments, strain Y246 not only exhibited strong inhibition against R. solani but also demonstrated remarkable inhibitory effects on A. alternata-induced tobacco brown spot and kiwifruit black spot, with impressive inhibition rates of 62.96% and 46.23%, respectively. Overall, these findings highlight the significant antifungal activity of B. safensis Y246 against R. solani. In addition, Y246 has an excellent antifungal stability, with an inhibition rate > 30% under different treatments (temperature, pH, UV). The results showed that the VOCs of strain Y246 had a strong inhibitory effect on the colony growth of R. solani, and the volatile substances produced by strain Y246 had an inhibitory effect on R. solani at rate of 70.19%. Based on these results, we can conclude that Y246 inhibits the normal growth of R. solani. These findings can provide valuable insights for developing sustainable agricultural strategies.

Comparison of Imaging Characteristics of Gangliogliomas between Child/Adolescent Group and Adult Group.

BACKGROUND: Ganglioglioma is a rare, slowly proliferating mixed glioneuronal tumor, with the highest incidence observed in children and young adults, but it can also occur in adults. OBJECTIVE: This study aimed to compare the imaging characteristics of ganglioglioma in children/adolescents and adults to facilitate radiographic diagnosis. METHODS: In this retrospective study, a total of 32 patients were included and divided into two groups: the child/adolescent group (age < 18 years, n=19) and the adult group (age ≥ 18 years, n=13). Various variables were analyzed, including maximum diameter, location, periphery, border, calcification, unenhanced CT attenuation, T1WI, T2WI/FLAIR, and DWI signal intensity, enhancement pattern, degree of enhancement, homogeneity of enhancement, solid/cystic component, peri-tumoral edema, intra-tumoral septa, peri-tumoral capsule, and intra-tumoral hemorrhage. RESULTS: Most gangliogliomas were situated in the peripheral regions, particularly in the temporal lobe. The majority exhibited hypointense/isointense signals on T1WI and hyperintense signals on T2WI/FLAIR and DWI, with predominantly heterogeneous nodular enhancement. Peri-tumoral edema was significantly less frequent in the child/adolescent group, while marked enhancement was significantly more common in the adult group. There was no significant difference in maximum diameter between the child/adolescent group and the adult group. CONCLUSION: Peri-tumoral edema was significantly less prevalent in the child/adolescent group, whereas marked enhancement was significantly more frequent in the adult group. To ensure accurate results, a larger case series should be conducted to validate our findings.

Associations of blood biomarkers with arterial stiffness in patients with diabetes mellitus: A population-based study.

BACKGROUND: Arterial stiffness contributes to additional cardiovascular risks in diabetic patients by triggering the loss of vascular and myocardial compliance and promoting endothelial dysfunction. Thus, prevention of arterial stiffness is a public health priority, and the identification of potential biomarkers may provide benefits for early prevention. This study investigates the relationships between serum laboratory tests and pulse wave velocity (PWV) tests. We also investigated the associations between PWV and all-cause mortality. METHODS: We examined a panel of 33 blood biomarkers among diabetic populations in the Atherosclerosis Risk in Communities Study. The carotid-femoral (cfPWV) and femoral-ankle PWV (faPWV) were measured using an automated cardiovascular screening device. The aortic-femoral arterial stiffness gradient (afSG) was calculated as faPWV divided by cfPWV. Biomarker levels were log-transformed and correlated with PWV. Cox proportional hazard models were employed for survival analysis. RESULTS: Among 1079 diabetic patients, biomarkers including high-density lipoprotein cholesterol, glycated hemoglobin, high-sensitivity troponin T, cystatin C, creatinine, and albuminuria were significantly correlated with afSG (R = 0.078, -0.193, -0.155, -0.153, -0.116, and -0.137, respectively) and cfPWV (R = -0.068, 0.175, 0.128, 0.066, 0.202, and 0.062, respectively). Compared with the lowest tertile of afSG, the risk of all-cause mortality was lower in the highest tertile (hazard ratio 0.543; 95% confidence interval 0.328-0.900). CONCLUSION: Certain biomarkers related to blood glucose monitoring, myocardial injury, and renal function significantly correlated with PWV, suggesting that these putative risk factors are likely to be important atherosclerosis mechanisms in diabetic patients. AfSG may be an independent predictor of mortality among diabetic populations.

Structure and mechanical properties of ladybird elytra as biological sandwich panels.

The armour of the ladybird, elytra, protect the body from injury and are well-adapted to flight. However, experimental methods to decipher their mechanical performances had been challenging due to the small size, making it unclear how the elytra balance mass and strength. Here, we provide insights to the relationship between the microstructure and multifunctional properties of the elytra by means of structural characterization, mechanical analysis and finite element simulations. Micromorphology analysis on the elytron revealed the thickness ratio of the upper lamination, middle layer and lower lamination is approximately 51:139:7. The upper lamination had multiple cross fibre layers and the thickness of each fibre layer is not the same. In addition, the tensile strength, elastic modulus, fracture strain, bending stiffness and hardness of elytra were obtained through in-situ tensile and nanoindentation-bending under the influence of multiple loading conditions, which also serve as references for finite element models. The finite element model revealed that structural factors such as thickness of each layer, angle of fibre layer and trabeculae are key to affecting the mechanical properties, but the effect is different. When the thickness of upper, middle and lower layers is the same, the tensile strength provided by unit mass of the model is 52.78% lower than that provided by elytra. These findings broaden the relationship between the structural and mechanical properties of the ladybird elytra, and are expected to inspire the development of sandwich structures in biomedical engineering.

Secure Inference on Homomorphically Encrypted Genotype Data with Encrypted Linear Models.

Background: Accurate models are crucial to estimate the phenotypes from high throughput genomic data. While the genetic and phenotypic data are sensitive, secure models are essential to protect the private information. Therefore, construct an accurate and secure model is significant in secure inference of phenotypes. Methods: We propose a secure inference protocol on homomorphically encrypted genotype data with encrypted linear models. Firstly, scale the genotype data by feature importance with Xgboost or Adaboost then train linear models to predict the phenotypes in plaintext. Secondly, encrypt the model parameters and test data with CKKS scheme for secure inference. Thirdly, predict the phenotypes under CKKS homomorphically encryption computation. Finally, decrypt the encrypted predictions by client to compute the 1-NRMSE/AUC for model evaluation. Results: 5 phenotypes of 3000 samples with 20390 variants are used to validate the performance of the secure inference protocol. The protocol achieves 0.9548, 0.9639, 0.9673 (1-NRMSE) for 3 continuous phenotypes and 0.9943, 0.99290 (AUC) for 2 category phenotypes in test data. Moreover, the protocol shows robust in 100 times of random sampling. Furthermore, the protocol achieves 0.9725 (the average accuracy) in an encrypted test set with 198 samples, and it only takes 4.32s for the overall inference. These help the protocol rank top one in the iDASH-2022 track2 challenge. Conclusion: We propose an accurate and secure protocol to predict the phenotype from genotype and it takes seconds to obtain hundreds of predictions for all phenotypes.

Laparoscopic revision of duct-to-mucosa pancreaticojejunostomy anastomotic stricture after laparoscopic pancreaticoduodenectomy.

PURPOSE: Pancreaticojejunostomy stricture (PJS) is an uncommon late complication of laparoscopic pancreaticoduodenectomy (LPD). The incidence, clinical characteristics, and managements of PJS after LPD are still unreported. METHODS: All patients undergoing LPD between January 2015 and December 2019 were identified from an institutional database. All pancreaticojejunostomies were performed using Bing's duct-to-mucosa anastomosis. PJS was diagnosed by computed tomography or magnetic resonance cholangio-pancreatography with secretin administration. Re-operation was performed in those patients with persistent abdominal pain and/or recurrent pancreatitis. Patients' demographic characteristics, perioperative outcomes, and follow-up outcomes were retrospectively collected. RESULTS: During the 5-year study period, 506 cases of LPD were performed. Among these patients, 13 patients (2.6%) were diagnosed with PJS. Only seven patients presented with abdominal pain and/or recurrent pancreatitis and underwent re-operation. The interval between the diagnosis of PJS and the original operation was 23 months. The median operative time was 140 min (range 90 to 210 min). The estimated blood loss was 40 ml (range 10 to 100 ml). The post-operative outcomes were favorable. Only one patient suffered from biochemical fistula. Six of these 7 patients (85.7%) reported complete pain resolution after the re-operation. The other patient reported partial resolution after surgery. All patients did not need to take analgesic drugs after the operation. CONCLUSION: PJS following LPD is a late complication that was underestimated. It is technically safe and clinically effective to perform laparoscopic revision of the PJS after LPD.

Long-Term Visit-To-Visit Blood Pressure Variability and Risk of Diabetes Mellitus in Chinese Population: A Retrospective Population-Based Study.

Objectives: To examine the association between visit-to-visit blood pressure variability (BPV) and incident diabetes mellitus (DM) risk in a Chinese population. Methods: Data comes from China Health and Nutrition Survey (n = 15,084). BPV was estimated as the average real variability (ARV) using at least three BP measurements from the year preceding the event and was divided into quartiles. Participants were also categorized into 9 groups on the basis of combinations of systolic BPV (SBPV) and diastolic BPV (DBPV) tertiles. Cox proportional hazards regression models were used. Results: During a median follow-up of 16.8 years, 1,030 (6.8%) participants developed diabetes (incidence rate: 4.65/1,000 person-years). The HRs (95% CIs) for the highest quartile (vs. the lowest quartile) of SBPV and DBPV were 1.60 (1.30-1.97) and 1.37 (1.13-1.67), respectively. Participants with both highest SBPV and DBPV tertile had an ≈89% higher risk of DM (HR, 1.89; 95% CI, 1.47-2.42) compared with those in the both SBPV and DBPV tertile 1 group. Conclusion: Higher SBP ARV and DBP ARV were independently associated with increased risk of incident DM, which was augmented when both presented together.

Prdm6 drives ductus arteriosus closure by promoting ductus arteriosus smooth muscle cell identity and contractility.

Based upon our demonstration that the smooth muscle cell-selective (SMC-selective) putative methyltransferase, Prdm6, interacts with myocardin-related transcription factor-A, we examined Prdm6's role in SMCs in vivo using cell type-specific knockout mouse models. Although SMC-specific depletion of Prdm6 in adult mice was well tolerated, Prdm6 depletion in Wnt1-expressing cells during development resulted in perinatal lethality and a completely penetrant patent ductus arteriosus (DA) phenotype. Lineage tracing experiments in Wnt1Cre2 Prdm6fl/fl ROSA26LacZ mice revealed normal neural crest-derived SMC investment of the outflow tract. In contrast, myography measurements on DA segments isolated from E18.5 embryos indicated that Prdm6 depletion significantly reduced DA tone and contractility. RNA-Seq analyses on DA and ascending aorta samples at E18.5 identified a DA-enriched gene program that included many SMC-selective contractile associated proteins that was downregulated by Prdm6 depletion. Chromatin immunoprecipitation-sequencing experiments in outflow tract SMCs demonstrated that 50% of the genes Prdm6 depletion altered contained Prdm6 binding sites. Finally, using several genome-wide data sets, we identified an SMC-selective enhancer within the Prdm6 third intron that exhibited allele-specific activity, providing evidence that rs17149944 may be the causal SNP for a cardiovascular disease GWAS locus identified within the human PRDM6 gene.