Efficacy of Weflow Embedded Branch Stents in the Treatment of Stanford Type B Dissection Involving Left Subclavian Artery.

Objective: Weflow embedded branch stent was used in the treatment of Stanford type B aortic dissection (TBAD) involving the left subclavian artery (LSA), and the effectiveness of the stent in the short and medium and term was observed. Methods: The clinical data of 22 patients with TBAD involving LSA treated with Weflow embedded branch stent from the First Hospital of Hebei Medical University from December 2020 to October 2021were retrospectively analyzed. The changes in systolic blood pressure of the left upper limb at the onset and postoperative period, the patency rate of left subclavian artery stent at 1, 6, and 12 months after surgery, the change of true and false lumen diameters, and the occurrence of complications were evaluated. Results: The patency rate of the left subclavian artery (LSA) branch stent was 100% at 1 month, 6 months, and 12 months after surgery. With the extension of postoperative time, the diameter of the aortic true lumen gradually increased. One month after surgery, the remodeling indexes of the aorta were improved, and with the extension of postoperative time, the diameter of the aortic false lumen decreased gradually. In the perioperative period, 1 case of vision, 1 case of insomnia, 1 case of retrograde type A dissection, 2 cases of type Ia endoleak, and no other new complications. During the follow-up, 2 patients with disappeared endoleak and 1 patient with retrograde dissection was in good condition after treatment. Conclusions: 1. Weflow embedded branch stent has good safety and reliability in the treatment of TBAD; 2. When LSA is involved, it can effectively improve the blood pressure of the patient's left upper limb, and the patency rate of the branch stent is good within 1 year; 3. Weflow embedded branch stent has a good short-term effect in aortic remodeling, and the medium- and long-term effect needs to be evaluated; 4. Weflow embedded branch stent had no obvious complications during the 1-year follow-up.

100-Phones: A Large VI-SLAM Dataset for Augmented Reality Towards Mass Deployment on Mobile Phones.

Visual-inertial SLAM (VI-SLAM) is a key technology for Augmented Reality (AR), which allows the AR device to recover its 6-DoF motion in real-time in order to render the virtual content with the corresponding pose. Nowadays, smartphones are still the mainstream devices for ordinary users to experience AR. However the current VI-SLAM methods, although performing well on high-end phones, still face robustness challenges when deployed on a larger stock of mid- and low-end phones. Existing VI-SLAM datasets use either very ideal sensors or only a limited number of devices for data collection, which cannot reflect the capability gaps that VI-SLAM methods need to solve when deployed on a large variety of phone models. This work proposes 100-Phones. the first VI-SLAM dataset covering a wide range of mainstream phones in the market. The dataset consists of 350 sequences collected by 100 different models of phones. Through analysis and experiments on the collected data, we conclude that the quality of visual-inertial data vary greatly among the mainstream phones, and the current open source VI-SLAM methods still have serious robustness issues when it comes to mass deployment on mobile phones. We release the dataset to facilitate the robustness improvement of VI-SLAM and to promote the mass popularization of AR. Project page: https://github.com/zju3dv/100-Phones.

Immunotoxicity of microplastics and polychlorinated biphenyls alone or in combination to Crassostrea gigas.

Microplastics (MPs) and polychlorinated biphenyls (PCBs) are pervasive pollutants in the marine environment, exerting adverse effects on marine organisms. While it is suggested that their exposure may compromise the immune responses of marine organisms, the cumulative immunotoxic effects remain uncertain. Additionally, the intricate mechanisms underlying the immunotoxicity of PCBs and MPs in marine organisms are not yet fully comprehended. To illuminate their combined biological impacts, Crassostrea gigas were exposed to 50 µg/L MPs (30-µm porous) alone, as well as 10 or 100 ng/L PCBs individually or in combination with 50 µg/L of MPs for 28 days. Our data demonstrated that oysters treated with the pollutants examined led to decreased total haemocyte count, inhibited phagocytosis of haemocytes, enhanced the intracellular contents of reactive oxygen species, lipid peroxidation and DNA damage, reduced lysozyme concentration and activity, gave rise to superoxide dismutase. Catalaseand glutathione S-transferaseactivity. The expression of three immune-related genes (NF-κB, TNF-α, TLR-6) was drastically suppressed by the PCBs and MPs treatment, while the apoptosis pathway-related genes (BAX and Caspase-3) showed a significant increase. In addition, compared to oysters treated with a single type of pollutant, coexposure to MPs and PCBs exerted more severe adverse impacts on all the parameters investigated, indicating a significant synergistic effect. Therefore, the risk of MPs and PCBs chemicals on marine organisms should be paid more attention.

Mechanistic insights into the C-type lectin receptor CLEC12A-mediated immune recognition of monosodium urate crystal.

CLEC12A, a member of the C-type lectin receptor family involved in immune homeostasis, recognizes MSU crystals released from dying cells. However, the molecular mechanism underlying the CLEC12A-mediated recognition of MSU crystals remains unclear. Herein, we reported the crystal structure of the human CLEC12A-C-type lectin-like domain (CTLD) and identified a unique "basic patch" site on CLEC12A-CTLD that is necessary for the binding of MSU crystals. Meanwhile, we determined the interaction strength between CLEC12A-CTLD and MSU crystals using single-molecule force spectroscopy. Furthermore, we found that CLEC12A clusters at the cell membrane and seems to serve as an internalizing receptor of MSU crystals. Altogether, these findings provide mechanistic insights for understanding the molecular mechanisms underlying the interplay between CLEC12A and MSU crystals.

An elastase-inhibiting, plaque-targeting and neutrophil-hitchhiking liposome against atherosclerosis.

Neutrophil extracellular traps (NETs) play a crucial role in the formation of vulnerable plaques and the development of atherosclerosis. Alleviating the pathological process of atherosclerosis by efficiently targeting neutrophils and inhibiting the activity of neutrophil elastase to inhibit NETs is relatively unexplored and is considered a novel therapeutic strategy with clinical significance. Sivelestat (SVT) is a second-generation competitive inhibitor of neutrophil elastase with high specificity. However, therapeutic effect of SVT on atherosclerosis is restricted because of the poor half-life and the lack of specific targeting. In this study, we construct a plaque-targeting and neutrophil-hitchhiking liposome (cRGD-SVT-Lipo) to improve the efficacy of SVT in vivo by modifying the cRGD peptide onto SVT loaded liposome, which was based on the interaction between cRGD peptide and integrin ανß3 on the surface of cells in blood and plaque, including epithelial cell, macrophage and neutrophils. The cRGD-SVT-Lipo could actively tend to or hitchhike neutrophils in situ to reach atherosclerotic plaque, which resulted in enhanced atherosclerotic plaque delivery. The cRGD-SVT-Lipo could also reduce plaque area, stabilize plaque, and ultimately alleviate atherosclerosis progression through efficiently inhibiting the activity of neutrophil elastase in atherosclerotic plaque. Therefore, this study provides a basis and targeting strategy for the treatment of neutrophil-related diseases. STATEMENT OF SIGNIFICANCE: Neutrophil extracellular traps (NETs)-inhibiting is a prospective therapeutic approach for atherosclerosis but has received little attention. The NETs can be inhibited by elastase-restraining. In this work, an intriguing system that delivers Sivelestat (SVT), a predominantly used neutrophil elastase inhibitor with poor targeting capability, is designed to provide the drug with plaque-targeting and neutrophil-hitchhiking capability. The result suggests that this system can effectively hinder the formation of NETs and delay the progression of atherosclerosis.

A bibliometric and visualization analysis of global research on postherpetic neuralgia from 2000 to 2022: A review.

Postherpetic neuralgia (PHN) represents a notable clinical challenge as it is the most prevalent and severe complication of herpes zoster (HZ). The primary objective was to investigate the current research status and hotspots of PHN research during the period from 2000 to 2022. The literature pertaining to PHN was gathered through the utilization of the Web of Science Core Collection, spanning from January 2000 to December 2022. The software, CiteSpace version 6.2.R2, was employed to produce visual depictions of publications related to PHN across various dimensions such as year, country/region, institution, journal, author, keyword, and reference. This study involved a total of 3505 papers. The USA held a dominant position in the production of scholarly articles. Argentina exhibited the highest frequency of participation in international collaboration. Out of all the institutions, Pfizer exhibited the highest degree of productivity. Harvard University exhibited the highest frequency of participation in international collaboration. The Pain exhibited the most noteworthy productivity rate and citation count among all other journals. Ralf Baron was identified as the most productive author, whereas DWORKIN RH attained the highest citation count. Contemporary scholarly investigations are predominantly centered on identifying risk factors, devising preventative measures, and exploring novel and secure methods of pain management. The current investigation has revealed the focal areas and patterns of studies pertaining to PHN. Presently, the research in this field is focused on identifying the risk factors and preventive measures for PHN, alongside exploring novel and secure pain management strategies.

Outcomes of Castor Single-Branched Stent Graft for Reconstruction of Multiple Supra-Aortic Branches in Aortic Arch Disease.

PURPOSE: To report the outcomes of a combination of Castor single-branched stent grafts with other techniques for the reconstruction of multiple supra-aortic branches in aortic arch disease. MATERIALS AND METHODS: Between December 2019 and December 2021, 20 patients with aortic arch disease underwent thoracic endovascular aortic repair (TEVAR) at our institution using a Castor single-branched stent graft combined with the fenestration, chimney, or bypass techniques. Thoracic endovascular aortic repair is indicated for complicated or acute type B aortic dissection (TBAD), nonruptured aneurysms with a maximum aneurysm diameter >5.5 cm or showing rapidly expanded, ruptured, or threatened aneurysms, and penetrating aortic ulcers (PAUs) with a maximal aortic diameter >5.5 cm or with PAUs >10 mm deep or >20 mm in diameter. Preoperative, intraoperative, and postoperative clinical data were recorded. RESULTS: The median age of the patients was 56 (range=52-69 years) years, and 19 patients were men. Seven patients underwent the Castor single-branched stent graft and left common carotid artery (LCCA) chimney technique, 8 patients underwent the Castor single-branched stent graft and fenestration technique, and 5 patients underwent the Castor single-branched stent graft and bypass technique. The technical success rate was 100%. Major adverse events included 2 endoleaks, 1 spinal cord ischemia, and 1 early-stage retrograde type A aortic dissection. No cerebral stroke-related complications were observed. The mortality rate was 10% (2/20 patients). One patient with thoracic aortic aneurysm (TAA) died because of a sudden decrease in oxygen saturation and blood pressure after surgery. Relatives declined autopsy, and the cause of death was not determined. Another patient died of a retrograde type A dissection after surgery. The median follow-up period was 6 months (range=3.5-12 months). During follow-up, 1 patient with type I endoleak underwent thoracotomy again after a year. The remaining patients recovered well. CONCLUSIONS: The combination of a Castor single-branched stent graft with fenestration, chimney, or bypass techniques may be an effective treatment for preserving multiple supra-aortic branches in aortic arch disease. CLINICAL IMPACT: This study introduced three methods of reconstruction of multiple supra-aortic branches using a Castor single-branched stent graft (Castor single-branched stent graft combined with fenestration, chimney, or bypass technique) and analysed their advantages and shortcomings to provide experience for the future treatment of aortic arch diseases.

Analysis of Acupoint Selection and Combinations in Acupuncture Treatment of Piriformis Syndrome: A Protocol for Data Mining.

Background: Piriformis syndrome (PS) is a neuromuscular condition characterized by discomfort in the gluteal region. The efficacy of acupuncture as a treatment modality for PS has been substantiated through a multitude of clinical trials. However, certain queries persist, such as the optimal approach for identifying the most efficacious acupoints. The objective of this study is to perform an initial data mining analysis aimed at identifying the optimal acupoint selection and combinations for the treatment of PS. Methods: We will search 7 electronic bibliographic databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database and Chongqing VIP Database) from inception to June 2023. We will select clinical trials that evaluate the efficacy of acupuncture therapy in the management of PS. Exclusions will be made for reviews, protocols, animal trials, case reports, systematic reviews, and meta-analyses. The primary outcome measure will be clinical outcomes associated with PS. Descriptive statistics will be performed in Excel 2019. Association rule analysis will be performed in SPSS Modeler 18.0. Exploratory factor analysis and cluster analysis will be performed in SPSS Statistics 26.0. Results: This study will investigate the most effective acupoint selection and combinations for patients with PS. Conclusion: Our findings will provide evidence for the effectiveness and potential treatment prescriptions of acupoint application for patients with PS, helping clinicians and patients make a more informed decision together.

Incidence and Clinical Features of Venous Thromboembolism in Inpatients with Mental Illness.

AIMS: We investigated the incidence and clinical features of venous thromboembolism (VTE) in inpatients with mental illnesses. METHODS: We retrospectively analyzed records of inpatients with mental illnesses and confirmed VTE at The First Hospital of Hebei Medical University between August 2018 and July 2022. We recorded demographic characteristics, psychosis-related conditions, and thrombus distribution. RESULTS: Among 12939 patients diagnosed with mental illness, 156 (1.21%) presented with VTE at the first visit or during the disease course. Crude VTE incidence varied significantly across mental illnesses, being highest in patients with organic mental disorders (5.20%), followed by emotional disorders (1.10%), and others (P < 0.001). Distal and proximal deep venous thromboses (DVT) occurred in 79.17% and 20.84% of patients, respectively. The Hamilton Depression Scale (HAMD) score was higher in patients with proximal DVT than in those with distal DVT (P < 0.001). On multivariate analysis, the HAMD score (odds ratio [OR] 1.173, confidence interval [CI] 1.100-1.251, P＜0.001) was a risk factor and the Hamilton Anxiety Scale (HAMA) (OR 0.862, CI 0.796-0.934, P＜0.001), a protective factor against DVT progression. CONCLUSION: VTE is not rare in patients with mental illnesses and is most commonly associated with organic mental disorders. Psychosis-related DVT typically shows a significantly high incidence of distal DVT. Prevention and early treatment in patients with severe depression and distal DVT can prevent DVT aggravation.

Oocytes could rearrange immunoglobulin production to survive over adverse environmental stimuli.

Immunoglobulins are key humoral immune molecules produced and secreted by B lymphocytes at various stages of differentiation. No research has reported whether immunoglobulins are present in the non-proliferative female germ cells-oocytes-and whether they are functionally important for oocyte quality, self-protection, and survival. Herein, we found that IgG was present in the oocytes of immunodeficient mice; the IgG-VDJ regions were highly variable between different oocytes, and H3K27Ac bound and regulated the IgG promoter region. Next, IgG mRNA and protein levels increased in response to LPS, and this increment was mediated by CR2 on the oocyte membrane. Finally, we revealed three aspects of the functional relevance of oocyte IgG: first, oocytes could upregulate IgG to counteract the increased ROS level induced by CSF1; second, oocytes could upregulate IgG in response to injected virus ssRNA to maintain mitochondrial integrity; third, upon bacterial infection, oocytes could secrete IgG, subsequently encompassing the bacteria, thus increasing survival compared to somatic cells. This study reveals for the first time that the female germ cells, oocytes, can independently adjust intrinsic IgG production to survive in adverse environments.

Two-minute walk distance reference equations for middle-aged and elderly Chinese individuals with obesity.

BACKGROUND AND OBJECTIVE: While the six-minute walk test (6MWT) is often used to assess exercise capacity, the less well-known two-minute walk test (2MWT) is more feasible for some patients. In previous studies, we developed reference equations for the two-minute walk distance (2MWD) for healthy Chinese adults. However, our study did not recruit people with obesity, and the reference equations did not apply to participants with a body mass index (BMI) > 30 kg/m2. The main objective of this study was to establish reference equations for the 2MWD among middle-aged and elderly Chinese individuals with obesity. METHODS: A total of 295 individuals were recruited. The participants underwent two 2MWTs, with the longer of the two 2MWDs used for further analyses. The reference equations for the 2MWD were developed using stepwise multiple regression analysis. The newly established equations for the 2MWD were then compared with the existing equations. RESULTS: The mean 2MWD of the participants was 176±20 m. Age and BMI were identified as independent factors that influenced the 2MWD and explained 28% and 32% of the variance in walking distance for the male and female groups, respectively. The reference equations for the 2MWD were as follows: [Formula: see text]. CONCLUSION: This study resulted in the development of reference equations for predicting 2MWD among middle-aged and elderly Chinese people with obesity. These equations will be a clinically valuable tool for evaluating functional capacity, determining prognoses and monitoring treatment in middle-aged and elderly Chinese people with obesity.

FBXW24 controls female meiotic prophase progression by regulating SYCP3 ubiquitination.

BACKGROUND: An impeccable female meiotic prophase is critical for producing a high-quality oocyte and, ultimately, a healthy newborn. SYCP3 is a key component of the synaptonemal complex regulating meiotic homologous recombination. However, what regulates SYCP3 stability is unknown. METHODS: Fertility assays, follicle counting, meiotic prophase stage (leptotene, zygotene, pachytene and diplotene) analysis and live imaging were employed to examine how FBXW24 knockout (KO) affect female fertility, follicle reserve, oocyte quality, meiotic prophase progression of female germ cells, and meiosis of oocytes. Western blot and immunostaining were used to examined the levels & signals (intensity, foci) of SYCP3 and multiple key DSB indicators & repair proteins (γH2AX, RPA2, p-CHK2, RAD51, MLH1, HORMAD1, TRIP13) after FBXW24 KO. Co-IP and immuno-EM were used to examined the interaction between FBXW24 and SYCP3; Mass spec was used to characterize the ubiquitination sites in SYCP3; In vivo & in vitro ubiquitination assays were utilized to determine the key sites in SYCP3 & FBXW24 for ubiquitination. RESULTS: Fbxw24-knockout (KO) female mice were infertile due to massive oocyte death upon meiosis entry. Fbxw24-KO oocytes were defective due to elevated DNA double-strand breaks (DSBs) and inseparable homologous chromosomes. Fbxw24-KO germ cells showed increased SYCP3 levels, delayed prophase progression, increased DSBs, and decreased crossover foci. Next, we found that FBXW24 directly binds and ubiquitinates SYCP3 to regulate its stability. In addition, several key residues important for SYCP3 ubiquitination and FBXW24 ubiquitinating activity were characterized. CONCLUSIONS: We proposed that FBXW24 regulates the timely degradation of SYCP3 to ensure normal crossover and DSB repair during pachytene. FBXW24-KO delayed SYCP3 degradation and DSB repair from pachytene until metaphase II (MII), ultimately causing failure in oocyte maturation, oocyte death, and infertility.

Nano-sponge-like liposomes remove cholesterol crystals for antiatherosclerosis.

Atherosclerotic cardiovascular diseases remain the leading causes of morbidity and mortality worldwide. Cholesterol crystals in atherosclerotic plaques play an essential role in atherosclerosis progression. However, no clinical drugs have been used for removing cholesterol crystals from plaque to counter atherosclerosis. Previous studies identified the hydrophobic domain of lipid bilayer in liposomes acted as sinks for solubilizing hydrophobic cholesterol. Moreover, adjusting the composition of the lipid bilayer in liposomes can enhance its hydrophobic molecule loading capacity. Therefore, in this study, ginsenosides Rb1 (Rb1), one of main active components of ginseng which has a similar structure to cholesterol, is anchored into soy phospholipids bilayer with its hydrophobic region to prepare nano-sponge-like liposomes (Rb1-LPs), aiming to amplify the solubilization of cholesterol in lipid bilayer. For targeting delivery to atherosclerotic plaques, Annexin V (AnxV), a protein that can specifically recognize phosphatidylserine upregulated in atherosclerotic plaques, is applied to decorate the surface of Rb1-LPs by click reaction to obtain the final preparation of AnxV-Rb1-LPs. The in vitro studies showed that incorporating Rb1 into lipid bilayer remarkably increased the affinity of the lipid bilayer to free cholesterol and the solubilization of cholesterol crystals. Additionally, nano-sponge-like liposomes could efficiently reduce the accumulation of cholesterol crystals and improve cholesterol efflux, finally inhibiting inflammation and apoptosis in cholesterol-laden cells. Furthermore, AnxV-Rb1-LPs could efficiently accumulate in atherosclerotic plaques after intravenous injection, exert nano-sponge-like functions to remove intra- and extracellular cholesterol crystals, ultimately alleviating inflammation and apoptosis in atherosclerotic plaques for antiatherosclerosis. Therefore, AnxV-Rb1-LPs provide a potential strategy for removing cholesterol crystals in atherosclerotic plaques and can be further utilized in other diseases with excessive cholesterol accumulation.

The Impaired Mechanism and Facilitated Therapies of Efferocytosis in Atherosclerosis.

ABSTRACT: Cardiovascular disease is responsible for the largest number of deaths worldwide, and atherosclerosis is the primary cause. Apoptotic cell accumulation in atherosclerotic plaques leads to necrotic core formation and plaque rupture. Emerging findings show that the progression of atherosclerosis appears to suppress the elimination of apoptotic cells. Mechanistically, the reduced edibility of apoptotic cells, insufficient phagocytic capacity of phagocytes, downregulation of bridging molecules, and dysfunction in the polarization of macrophages lead to impaired efferocytosis in atherosclerotic plaques. This review focuses on the characteristics of efferocytosis in plaques and the therapeutic strategies aimed at promoting efferocytosis in atherosclerosis, which would provide novel insights for the development of antiatherosclerotic drugs based on efferocytosis.

Reference equations for the six-minute walking distance in obese Chinese subjects more than 40 years old.

BACKGROUND: Studies have shown that the reference equations for the six-minute walking distance (6MWD), which were mainly derived from healthy, normal-weight people, are not suitable for individuals with obesity. The main purpose of this study was to establish reference equations for the 6MWD in obese Chinese subjects. METHODS: In our study, a total of 214 individuals with obesity performed the six-minute walking tests (6MWTs) according to the American thoracic society (ATS) guidelines, and the longer 6MWD was used for further analysis. The reference equations for the 6MWD were developed using stepwise multiple regression analysis. The newly established equations for the 6MWD were compared to the existing prediction equations. RESULTS: The mean 6MWD for the cohort was 523 ± 56 m. We found that the reliability of two 6MWTs was good. Age and BMI were identified as independent factors, and explained 31% and 27% of the variance in the 6MWD for the male and female participants, respectively. Thus, the reference equations reported in the previous studies did not accurately predict the 6MWD in our subjects. CONCLUSION: Our study was the first to describe the 6MWD in obese Chinese subjects and to propose new predictive equations. These established equations can improve the assessment of the health of obese Chinese patients whose exercise capacity is affected by the disease. LEVEL OF EVIDENCE: III, Cohort study.

Comparative Transcriptomic Analysis Reveals the Regulated Expression Profiles in Oreochromis niloticus in Response to Coinfection of Streptococcus agalactiae and Streptococcus iniae.

Tilapia (Oreochromis sp.) is one of the important economical fishes in the world. Streptococcosis is commonly found in tilapia, causing severe and devastating effects in tilapia cultures. Streptococcus agalactiae and Streptococcus iniae are the predominant pathogens causing tilapia streptococcosis. To understand the molecular mechanisms underlying differential streptococcal infection patterns, Nile tilapias (Oreochromis niloticus) were infected by 1 × 107 CFU/mL S. agalactiae, 1 × 107 CFU/mL S. iniae, and 1 × 107 CFU/mL S. agalactiae and S. iniae (1:1), respectively, and transcriptome analysis was conducted to the intestine samples of Nile tilapia (Oreochromis niloticus) at 6, 12, 24 h, and 7 days post-infection. A total of 6,185 genes that differentially expressed among groups were identified. Eight differentially expressed genes (DEGs) including E3 ubiquitin-protein ligase TRIM39-like, C-X-C motif chemokine 10-like(CXCL 10), C-C motif chemokine 19-like, interleukin-1 beta-like, IgM heavy chain VH region, partial, IgG Fc-binding protein, proteasome subunit beta type-8 (PSMB8), and ATP synthase F(0) complex subunit B1, mitochondrial that involved in the immune system were selected, and their expression levels in the coinfection group were significantly higher than those in either of the single infection groups. These genes were associated with four different KEGG pathways. Additionally, the differential expression of eight DEGs was validated by using the RT-qPCR approach, and their immunological importance was discussed. The results provided insights into the responses of tilapia against S. agalactiae and S. iniae at the transcriptome level, promoting our better understanding of immune responses for aquatic animal against Streptococcus.

PKG II secreted via the classical endoplasmic reticulum-Golgi apparatus secretory pathway blocks the activation of EGFR through phosporalting its threonine 406 and has an anti-tumor effect.

BACKGROUND: Protein kinase G type II (PKG II) is a serine/threonine-protein kinase that was originally isolated from the small intestinal mucosa with primary functions in the secretion of small intestinal mucosal cells, secretion of renin and aldosterone, and chondrocyte activities. Recent studies have shown that PKG II exerts anti-tumor effects, while a previous study by our group confirmed that PKG II inhibited the proliferation and migration of cancer cells. Interestingly, PKG II, which was typically bound to the intracellular side of the membrane, was detected in the serum and cell culture medium as a diagnostic biomarker of tumor growth. Thus, the aim of the present study was to elucidate the function and the targets of PKG II, and the mechanism underlying the secretion of this kinase. METHODS: Construction of peptides and plasmids, RNA interference, Immunoelectron microscopy, Co-immunoprecipitation, N-glycosylation assay and Isolation of the Golgi apparatus were applied to investigate the secretory mechanism, and the targets and function of PKG II. RESULTS: PKG II was secreted by enterochromaffin (EC) cells, which were components of the endocrine system in the gastrointestinal tract. Myristoylation of glycine 2 and the N-terminal sequence, especially the amino acids 3-30, acted as a signal peptide to induce the secretion of PKG II via the conventional protein secretory pathway. Moreover, recombinant PKG II inhibited the epidermal growth factor (EGF)-induced activation of the EGF receptor via phosphorylating the T406 of the extracellular domain and blocked EGF-triggered proliferation of various cancer cells. CONCLUSIONS: These results revealed a correlation between the endocrine system and the secretion of protein kinase, suggesting a novel protein secretory pathway. The resuls also indicated that secreted PKG II was a potential diagnostic biomarker and an inhibitor of tumor.

Comparison of Modified Above-Knee and Conventional Surgery with the Stripping of the Great Saphenous Vein of Varicose Veins of the Lower Extremities: A Retrospective Study.

OBJECTIVE: To compare the clinical effects of modified above-knee and conventional surgery with the stripping of the great saphenous vein of varicose veins of the lower extremities. METHODS: Clinical data of patients with a varicose vein of the lower extremity from May 2016 to May 2018 were collected. A retrospective study was conducted on the patients receiving modified above-knee and conventional surgery with the great saphenous vein stripping. The baseline characteristics and long-term follow-up data were compared between the groups. RESULTS: There were no significant differences in baseline characteristics between the two groups (P > 0.05). The surgeries were successfully performed by the same group of surgeons under local anesthesia and neuraxial anesthesia. The hospital stay, operation time, intraoperative blood loss, total length, and number of incisions in the above-knee group were comparable to those in the conventional surgery group (P > 0.05). The incidence of saphenous nerve injury and subcutaneous hematoma in the above-knee group was lower than that in the conventional surgery group (P < 0.05). There were no significant differences in recurrent varicose vein incidences (P > 0.05). After surgery, the venous clinical severity score (VCSS) and chronic venous insufficiency questionnaire (CIVIQ-14) scores of both groups were higher than those before operation (P < 0.05). There was no significant difference in VCSS score or CIVIQ-14 scores between the two groups postoperation (P > 0.05). At 24 months after surgery, the above-knee group (71.8%) and conventional surgery group (73.2%) resulted in changes of at least two CEAP-C clinical classes lower than baseline, respectively. CONCLUSION: The modified above-knee technique can ensure clinical outcomes, reduce intraoperative blood loss and complication incidences, and shorten the operative time. This gives evidence that the modified above-knee technique is worthy of clinical application.

Gm364 coordinates MIB2/DLL3/Notch2 to regulate female fertility through AKT activation.

Many integral membrane proteins might act as indispensable coordinators in specific functional microdomains to maintain the normal operation of known receptors, such as Notch. Gm364 is a multi-pass transmembrane protein that has been screened as a potential female fertility factor. However, there have been no reports to date about its function in female fertility. Here, we found that global knockout of Gm364 decreased the numbers of primordial follicles and growing follicles, impaired oocyte quality as indicated by increased ROS and γ-H2AX, decreased mitochondrial membrane potential, decreased oocyte maturation, and increased aneuploidy. Mechanistically, Gm364 directly binds and anchors MIB2, a ubiquitin ligase, on the membrane. Subsequently, membrane MIB2 ubiquitinates and activates DLL3. Next, the activated DLL3 binds and activates Notch2, which is subsequently cleaved within the cytoplasm to produce NICD2, the intracellular active domain of Notch2. Finally, NICD2 can directly activate AKT within the cytoplasm to regulate oocyte meiosis and quality.

Quantitative phosphoproteomics reveals GSK3A substrate network is involved in the cryodamage of sperm motility.

During sperm cryopreservation, the most significant phenotype of cryodamage is the decrease in sperm motility. Several proteomics studies have already been performed to search for key regulators at the protein level. However, sperm functions are known to be highly regulated by phosphorylation signaling. Here, we constructed a quantitative phosphoproteome to investigate the expression change of phosphorylated sites during sperm cryopreservation. A total of 3107 phosphorylated sites are identified and 848 of them are found to be significantly differentially expressed (DE). Bioinformatics analysis showed that the corresponding genes of these regulated sites are highly associated with sperm motility, providing a connection between the molecular basis and the phenotype of cryodamage. We then performed kinase enrichment analysis and successfully identified glycogen synthase kinase-3α (GSK3A) as the key kinase that may play an important role in the regulation of sperm motility. We further constructed a GSK3A centric network that could help us better understand the molecular mechanism of cryodamage in sperm motility. Finally, we also verified that GSK3A was abnormally activated during this process. The presented phosphoproteome and functional associations provide abundant research resources for us to learn the regulation of sperm functions, as well as to optimize the cryoprotectant for sperm cryopreservation.