Phase division and recognition of crystal HRTEM images based on machine learning and deep learning.

The High Resolution Transmission Electron Microscope (HRTEM) images provide valuable insights into the atomic microstructure, dislocation patterns, defects, and phase characteristics of materials. However, the current analysis and research of HRTEM images of crystal materials heavily rely on manual expertise, which is labor-intensive and susceptible to subjective errors. This study proposes a combined machine learning and deep learning approach to automatically partition the same phase regions in crystal HRTEM images. The entire image is traversed by a sliding window to compute the amplitude spectrum of the Fast Fourier Transform (FFT) in each window. The generated data is transformed into a 4-dimensional (4D) format. Principal component analysis (PCA) on this 4D data estimates the number of feature regions. Non-negative matrix factorization (NMF) then decomposes the data into a coefficient matrix representing feature region distribution, and a feature matrix corresponding to the FFT magnitude spectra. Phase recognition based on deep learning enables identifying the phase of each feature region, thereby achieving automatic segmentation and recognition of phase regions in HRTEM images of crystals. Experiments on zirconium and oxide nanoparticle HRTEM images demonstrate the proposed method achieve the consistency of manual analysis. Code and supplementary material are available at https://github.com/rememberBr/HRTEM2.

Clinical characteristics and phylogenetic analysis of human enteric adenovirus type 41 (HAdV-F41) from children with gastroenteritis during SARS-CoV-2 pandemic.

Human adenovirus type 41 (HAdV-F41) usually causes pediatrics gastroenteritis. However, it was reported to be associated with the outbreaks of severe acute hepatitis of unknown aetiology (SAHUA) in pediatrics during COVID-19 pandemic. In this study, we investigated the prevalence of enteric HAdV-F41 in 37,920 paediatric gastroenteritis cases from 2017 to 2022 in Guangzhou, China. All children presented were tested negative for SARS-CoV-2 during the "zero-COVID" period. The main clinical symptom of the children was diarrhea (96.5%). No fatalities nor liver abnormal symptoms was found. In 2021, one year since the pandemic of COVID-19, the prevalence of HAdV-F41 abruptly increased from 3.71% to 8.64% (P < 0.001). All of HAdV-F41 circulating worldwide were classified into eight different subtypes (G1-G8) based on the phylogenetic clustering permutation of the four capsid genes of HAdV-F41. G3 was the predominant subtype (56.2%; 77/137). CRV5 isolates from SAHUA cases belong to this subtype, in which N312D and H335D mutations in the short fiber knob were identified in both Guangzhou and CRV5 isolates, presumably changing the virus tropism by directly interacting with the heparin sulfate (HS) receptor. Additionally, a novel recombinant G6 subtype, which is unique and only circulating in China was first identified in this study. This is the first study highlighting the prevalence of HAdV-F41 in paediatric cases of gastroenteritis during COVID-19 pandemic in China. The clinical and viral evolution finding of HAdV-F41 provide insight into the clinical characteristics of children with HAdV-F41 infections as well as the uncertain role of HAdV-F41 in the cause of SAHUA.

Clinical characteristics and risk factors in patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases.

Objective: To investigate the clinical characteristics and risk factors of patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases. Methods: A retrospective analysis of general clinical data was conducted on patients with SARS-CoV-2 omicron infection complicated with hypertension, coronary heart disease, and heart failure admitted to one hospital in Guangdong Province from December 1, 2022, to February 28, 2023. Clinical symptoms, laboratory tests, imaging examinations, treatment, and clinical outcomes were collected. Multivariate logistic regression analysis was used to analyze the risk factors for mortality in patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases. ROC curves were drawn to evaluate the predictive value of CRP, D-dimer, and CK-MB in predicting the risk of death. Results: A total of 364 confirmed cases were included, divided into the asymptomatic group, mild to moderate group, and severe to critically ill group based on the symptoms of COVID-19. There were 216 males (59.34%) and 148 females (40.66%), with a median age of 75 years. The differences between the three groups in terms of sex and age were statistically significant (p < 0.05). The top three underlying diseases were hypertension (288 cases, 79.12%), coronary heart disease (100 cases, 27.47%), and diabetes (84 cases, 23.08%). The differences in unvaccinated and triple-vaccinated patients among the three groups were statistically significant (p < 0.05). The common respiratory symptoms were cough in 237 cases (65.11%) and sputum production in 199 cases (54.67%). In terms of laboratory tests, there were statistically significant differences in neutrophils, lymphocytes, red blood cells, C-reactive protein, D-dimer, aspartate aminotransferase, and creatinine among the three groups (p < 0.05). In imaging examinations, there were statistically significant differences among the three groups in terms of unilateral pulmonary inflammation, bilateral pulmonary inflammation, and bilateral pleural effusion (p < 0.05). There were statistically significant differences among the three groups in terms of antibiotic treatment, steroid treatment, oxygen therapy, nasal cannula oxygen inhalation therapy, non-invasive ventilation, and tracheal intubation ventilation (p < 0.05). Regarding clinical outcomes, there were statistically significant differences among the three groups in terms of mortality (p < 0.05). Multivariate logistic regression analysis showed that CRP (OR = 1.012, 95% CI = 1.004-1.019) and D-dimer (OR = 1.117, 95% CI = 1.021-1.224) were independent risk factors for patient mortality. The predictive value of CRP, D-dimer, and CK-MB for the risk of death was assessed. D-dimer had the highest sensitivity (95.8%) in predicting patient mortality risk, while CRP had the highest specificity (84.4%). Conclusion: For patients with COVID-19 and concomitant cardiovascular diseases without contraindications, early administration of COVID-19 vaccines and booster shots can effectively reduce the mortality rate of severe cases. Monitoring biomarkers such as CRP, D-dimer, and CK-MB and promptly providing appropriate care can help mitigate the risk of mortality in patients.

A comprehensive analysis of GAS2 family members identifies that GAS2L1 is a novel biomarker and promotes the proliferation of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common primary liver cancer with a high incidence and mortality. Members of the growth-arresting-specific 2 (GAS2) family are involved in various biological processes in human malignancies. To date, there is only a limited amount of information available about the expression profile and clinical importance of GAS2 family in HCC. In this study, we found that GAS2L1 and GAS2L3 were distinctly upregulated in HCC specimens compared to non-tumor specimens. Pan-cancer assays indicated that GAS2L1 and GAS2L3 were highly expressed in most cancers. The Pearson's correlation revealed that the expressions of GAS2, GAS2L1 and GAS2L2 were negatively associated with methylation levels. Survival assays indicated that GAS2L1 and GAS2L3 were independent prognostic factors for HCC patients. Immune cell infiltration analysis revealed that GAS2, GAS2L1 and GAS2L3 were associated with several immune cells. Finally, we confirmed that GAS2L1 was highly expressed in HCC cells and its knockdown suppressed the proliferation of HCC cells. Taken together, our findings suggested the expression patterns and prognostic values of GAS2 members in HCC, providing insights for further study of the GAS2 family as sensitive diagnostic and prognostic markers for HCC.

Panax quinquefolius saponins and panax notoginseng saponins attenuate myocardial hypoxia-reoxygenation injury by reducing excessive mitophagy.

OBJECTIVE: Panax quinquefolius saponins (PQS) and Panax notoginseng saponins (PNS) are key bioactive compounds in Panax quinquefolius L. and Panax notoginseng, commonly used in the treatment of clinical ischemic heart disease. However, their potential in mitigating myocardial ischemia-reperfusion injury remains uncertain. This study aims to evaluate the protective effects of combined PQS and PNS administration in myocardial hypoxia/reoxygenation (H/R) injury and explore the underlying mechanisms. METHODS: To investigate the involvement of HIF-1α/BNIP3 mitophagy pathway in the myocardial protection conferred by PNS and PQS, we employed small interfering BNIP3 (siBNIP3) to silence key proteins of the pathway. H9C2 cells were categorized into four groups: control, H/R, H/R + PQS + PNS, and H/R + PQS + PNS+siBNIP3. Cell viability was assessed by Cell Counting Kit-8, apoptosis rates determined via flow cytometry, mitochondrial membrane potential assessed with the JC-1 fluorescent probes, intracellular reactive oxygen species detected with 2',7'-dichlorodihydrofluorescein diacetate, mitochondrial superoxide production quantified with MitoSOX Red, and autophagic flux monitored with mRFP-GFP-LC3 adenoviral vectors. Autophagosomes and their ultrastructure were visualized through transmission electron microscopy. Moreover, mRNA and protein levels were analyzed via real-time PCR and Western blotting. RESULTS: PQS + PNS administration significantly increased cell viability, reduced apoptosis, lowered reactive oxygen species levels and mitochondrial superoxide production, mitigated mitochondrial dysfunction, and induced autophagic flux. Notably, siBNIP3 intervention did not counteract the cardioprotective effect of PQS + PNS. The PQS + PNS group showed downregulated mRNA expression of HIF-1α and BNIP3, along with reduced HIF-1α protein expression compared to the H/R group. CONCLUSIONS: PQS + PNS protects against myocardial H/R injury, potentially by downregulating mitophagy through the HIF-1α/BNIP3 pathway.

Four and a half LIM domains 2 (FHL2) attenuates tumorigenesis of gastrointestinal stromal tumors (GISTs) by negatively regulating KIT signaling.

Gastrointestinal stromal tumors (GISTs) are predominately induced by KIT mutants. In this study, we found that four and a half LIM domains 2 (FHL2) was highly expressed in GISTs and KIT signaling dramatically increased FHL2 transcription while FHL2 inhibited KIT transcription. In addition, our results showed that FHL2 associated with KIT and increased the ubiquitination of both wild-type KIT and primary KIT mutants in GISTs, leading to decreased expression and activation of KIT although primary KIT mutants were less inhibited by FHL2 than wild-type KIT. In the animal experiments, loss of FHL2 expression in mice carrying germline KIT/V558A mutation which can develop GISTs resulted in increased tumor growth, but increased sensitivity of GISTs to imatinib treatment which is used as the first-line targeted therapy of GISTs, suggesting that FHL2 plays a role in the response of GISTs to KIT inhibitor. Unlike wild-type KIT and primary KIT mutants, we further found that FHL2 didn't alter the expression and activation of drug-resistant secondary KIT mutants. Taken together, our results indicated that FHL2 acts as the negative feedback of KIT signaling in GISTs while primary KIT mutants are less sensitive and secondary KIT mutants are resistant to the inhibition of FHL2.

Clinical analysis of a new multifunctional instrument set for gasless endoscopic thyroidectomy with two different approaches.

BACKGROUND: Following the rapid development of endoscopic thyroidectomy techniques, various surgical procedures have been developed (e.g., transoral, submandibular, areolar, axillary, retroauricular, and combined procedures), and each of these procedures has its own advantages. In recent years, gasless endoscopic thyroidectomy has emerged as a feasible procedure, and it has replaced traditional CO2 insufflation approaches because of advantages such as stable cavity construction, pollution reduction, resource saving, and risk reduction. However, each gasless procedure requires special instruments for cavity construction, and this results in enormous wastage of medical resources. In the present study, we introduced a set of instruments developed by our team. This set of instruments is designed to be compatible with the current gasless endoscopic thyroidectomy approaches, including transoral, submandibular, transareolar, transaxillary, retroauricular, combined, and lateral cervical lymph node dissection. Here, we introduced this set of instruments for two gasless endoscopic thyroidectomy procedures (transaxillary and transareolar). Following the incorporation of this set of instruments in regular clinical practice, it could be used for more gasless endoscopic thyroidectomy procedures in the future. OBJECTIVE: To investigate the feasibility, safety, and efficacy of the self-developed instruments for gasless endoscopic thyroidectomy in two different approaches. METHODS: A total of 180 patients diagnosed to have papillary thyroid carcinoma (PTC) between January 2020 and April 2022 were retrospectively investigated. The patients were assigned to a gasless transaxillary group (group A) and a gasless transareolar group (group B). The same gasless endoscopic-assisted instruments were used for both groups. The clinical characteristics, treatment results, and complications were compared between the two groups. RESULTS: All 180 patients were successfully operated. The extent of surgical resection in all patients was the same: "unilateral glandular lobectomy + isthmus combined with ipsilateral central zone lymph node dissection." There were 130 and 50 patients in group A and group B, respectively; one patient in the former group was converted to open surgery due to intraoperative bleeding. No significant difference was observed between the two groups in terms of gender, age, body mass index (BMI), education level, and proportion of concomitant Hashimoto's thyroiditis (P > 0.05). The establishment of cavity time was significantly longer in group A than in group B (35.62 ± 5.07 min vs. 17.46 ± 2.55 min, P < 0.01). The number of lymph nodes cleared was slightly less in group A than in group B (4.06 ± 2.93 vs. 4.52 ± 2.38, P = 0.07). Moreover, the two groups showed no significant differences (P > 0.05) in the total operative time (145.54 ± 45.11 min vs. 143.06 ± 46.70 min), tumor size (0.68 ± 0.46 cm vs. 0.71 ± 0.49 cm), postoperative hospital stay (4.08 ± 1.48 days vs. 3.72 ± 1.07 days), vocal cord paralysis [4 (3.1%) vs. 2 (4%)], postoperative swallowing discomfort [24 (18.5%) vs. 5 (10%)], and postoperative recurrence and satisfaction scores (3.27 ± 1.52 vs. 3.28 ± 1.53). CONCLUSION: Although the two approaches of gasless endoscopic surgery have different operative paths and different time periods for cavity construction, both approaches are similar in terms of the principle of cavity construction, safe and reliable postoperative efficacy, and good cosmetic effect. Therefore, the same set of instruments can be used to complete the surgery in both approaches, thus saving medical resources and facilitating the popularization of this technology.

[Development and Clinical Application of Multifunctional Inflation-Free Lumpectomy Aid].

To investigate the value of self-developed air-free laparoscopic auxiliary instruments in the clinical application of thyroid diseases. The clinical data of 70 transaxillary and 45 transareolar air-free laparoscopic surgeries for thyroid cancer and 40 conventional open surgeries were retrospectively compared. The transaxillary and transareolar laparoscopic groups had significantly longer operative times than the open group, while the postoperative satisfaction was higher in the endoscopic group than in the open group. This set of instruments has advantage of novel design, scientific structure, safe application. It can be compatible with a variety of thyroid and breast air-free laparoscopic procedures, which can promote the development and popularization of laparoscopic technology.

Cell-permeable PI3 kinase competitive peptide inhibits KIT mutant mediated tumorigenesis of gastrointestinal stromal tumor (GIST).

BACKGROUND: Mutations in the receptor tyrosine kinase KIT are the main cause of gastrointestinal stromal tumor (GIST), and the KIT mutants mediated PI3 kinase activation plays a key role in the tumorigenesis of GIST. In this study, we aimed to block PI3 kinase activation by cell-permeable peptide and investigate its possible application in the treatment of GIST. METHODS AND RESULTS: We designed cell-permeable peptides based on the binding domain of PI3 kinase subunit p85 to KIT or PI3 kinase subunit p110, respectively, in order to compete for the binding between p85 and KIT or p110 and therefore inhibit the activation of PI3 kinases mediated by KIT. The results showed that the peptide can penetrate the cells, and inhibit the activation of PI3 kinases, leading to reduced cell survival and cell proliferation mediated by KIT mutants in vitro. Treatment of mice carrying germline KIT/V558A mutation, which can develop GIST, with the peptide that can compete for the binding between p85 and p110, led to reduced tumorigenesis of GIST. The peptide can further enhance the inhibition of the tumor growth by imatinib which is used as the first line targeted therapy of GIST. CONCLUSIONS: Our results showed that cell-permeable PI3 kinase competitive peptide can inhibit KIT-mediated PI3 kinase activation and tumorigenesis of GIST, providing a rationale to further test the peptide in the treatment of GIST and even other tumors with over-activation of PI3 kinases.

Job preferences of master of public health students in China: a discrete choice experiment.

BACKGROUND: The shortage of public health personnel and the uneven distribution between urban and rural areas are thorny issues in China. Master of public health (MPH) is an integral part of public health human resources in the future, and it is of far-reaching significance to discuss their work preferences. The present study wants to investigate the job preference of MPH, understand the relative importance of different job attributes, and then put forward targeted incentive measures. METHODS: Discrete choice experiment (DCE) was used to evaluate the job preference of MPHs in two medical colleges in Liaoning Province. Attributes include employment location, bianzhi, working environment, career development prospects, work value and monthly income. Thirty-six choice sets were developed using a fractional factorial design. Mixed logit models were used to analysis the DCE data. RESULTS: The final sample comprised 327 MPHs. All the attributes and levels included in the study are statistically significant. Monthly income is the most important factor for MPHs. For non-economic factors, they value career development prospects most, followed by the employment location. Respondents' preferences are heterogeneous and influenced by individual characteristics. Subgroup analysis showed that respondents from different family backgrounds have different job preferences. Policy simulation suggested that respondents were most sensitive to a salary increase, and the combination of several non-economic factors can also achieve the same effect. CONCLUSIONS: Economic factors and non-economic factors significantly affect the job preference of MPHs. To alleviate the shortage and uneven distribution of public health personnel, more effective policy intervention should comprehensively consider the incentive measures of the work itself and pay attention to the individual characteristics and family backgrounds of the target object.

Interaction of 5-HTTLPR and SLE disease status on resting-state brain function.

BACKGROUND: Neuropsychiatric involvement in systemic lupus erythematosus (SLE) is a common clinical manifestation. In SLE patients, cerebral function is a more sensitive predictor of central nervous system damage, and abnormalities in cerebral function may be apparent before substantial neuropsychiatric symptoms occur. The 5-hydroxynyptamine(5-HT) system has the ability to interact with the majority of the neurochemical systems in the central nervous system (CNS), influencing brain function. Serotonin transporter gene-linked polymorphic region (5-HTTLPR) is an essential element of the 5-HT system gene polymorphism and is directly related to the control of 5-hydroxytryptamine transporter (5-HTT)gene expression. The relationship between 5-HTTLPR and functional brain measurements in SLE patients requires more investigation because it is one of the most attractive imaging genetics targets for shedding light on the pathophysiology of neuropsychiatric lupus. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) images were collected from 51 SLE patients without obvious neuropsychiatric manifestations and 44 healthy volunteers. Regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), and fractional amplitude of low-frequency fluctuations (fALFF) were selected as indicators for evaluating brain function. In accordance with the Anatomical Automatic Labeling template, the gray matter was divided into 116 regions. The mean ReHo value, mean ALFF value, and mean fALFF value of each brain region were extracted. 5-HTTLPR genotypes of all research objects were tested by polymerase chain reaction and agarose gel electrophoresis. Two-way analysis of covariance was used to investigate whether there is an interaction effect between SLE disease status and 5-HTTLPR genotype on resting-state brain function. RESULTS: In SLE patients with S/S homozygosity, there were notably lower mean ReHo, mean ALFF, and mean fALFF values observed in the right parietal, inferior angular gyrus, and the right paracentral lobule compared to healthy controls. However, this distinction was not evident among carriers of the L allele. Within the S/S genotype, SLE patients exhibited decreased mean ReHo in the left posterior cingulate gyrus, reduced mean fALFF in the left caudate nucleus, and diminished mean ALFF in the left temporal pole: superior temporal gyrus, in contrast to the HC group. Conversely, no such differences were discerned among carriers of the L allele. Notably, among L allele carriers, SLE patients displayed a higher mean ReHo value in the right hippocampus compared to the HC group, while demonstrating a lower mean ALFF value in the left medial and paracingulate gyrus in contrast to the HC group. Conversely, these differences were not apparent among S/S homozygotes. CONCLUSIONS: Brain function in the right parietal and inferior angular gyrus and the right paracentral lobule is affected by the interaction effect of SLE disease status and 5-HTTLPR genotype.

Giant unilateral electric-field control of magnetic anisotropy in MgO/Rh2CoSb heterojunctions.

A large voltage-controlled magnetic anisotropy (VCMA) effect is highly desirable for applications of voltage-torque magnetic random access memory. In this work, the dependence of magnetic anisotropy (MA) on the electric field in a MgO-based heterojunction consisting of a new Heusler alloy, Rh2CoSb, is studied using first-principles calculations. We find that the Rh-terminated MgO/Rh2CoSb heterojunction has a perpendicular MA and a giant VCMA coefficient of 7024 fJ V-1 m-1. Furthermore, the VCMA coefficient shows a characteristic of dependence on the electric-field direction. The origins of these behaviors are elucidated by orbital-resolved MA and second-order perturbation theoretical analysis. As the spin-down states of the in-plane orbital, dxy, are close to the Fermi level, the shift of these states induced by the electric field gives rise to significant changes of magnetic anisotropy energy, which is mainly responsible for the giant VCMA effect.

Bioparameter-directed nanoformulations as MRI CAs enable the specific visualization of hypoxic tumour.

A malignant tumour has hypoxic cells of varying degrees. The more severe the hypoxic degree, the more difficult the prognosis of the tumour and the higher the recurrence rate. Therefore, tumour hypoxia imaging is crucial. Magnetic resonance imaging (MRI) shows its strength in high resolution, depth of penetration and noninvasiveness. However, it needs more excellent contrast agents (CAs) to combat the complex tumour microenvironment (TME) and increased targeting of tumours to enhance clinical safety. Many research studies have focused on developing hypoxia-responsive MRI CAs that take advantage of the unique characteristics of hypoxic tumours. The low oxygen pressure, acidic TME, and up-regulated redox molecule levels found in hypoxic tumours serve as biological stimuli for nanoformulations that can accurately image the hypoxic region. This review highlights the importance of developing bioparameter-directed nanoformulations as MRI CAs for accurate tumour diagnosis. The design strategies and mechanisms of tumour-hypoxia imaging with nanoformulations are exemplified, with a focus on pH-responsiveness, redox-responsiveness, and p(O2)-responsiveness. The promising future of bioparameter-responsive nanoformulations for accurate tumour diagnosis and personalised cancer treatment is discussed.

Designing Smart Iron Oxide Nanoparticles for MR Imaging of Tumors.

Iron oxide nanoparticles (IONPs) possess unique magnetism and good biocompatibility, and they have been widely applied as contrast agents (CAs) for magnetic resonance imaging (MRI). Traditional CAs typically show a fixed enhanced signal, thus exhibiting the limitations of low sensitivity and a lack of specificity. Nowadays, the progress of stimulus-responsive IONPs allows alteration of the relaxation signal in response to internal stimuli of the tumor, or external stimuli, thus providing an opportunity to overcome those limitations. This review summarizes the current status of smart IONPs as tumor imaging MRI CAs that exhibit responsiveness to endogenous stimuli, such as pH, hypoxia, glutathione, and enzymes, or exogenous stimuli, such as magnets, light, and so on. We discuss the challenges and future opportunities for IONPs as MRI CAs and comprehensively illustrate the applications of these stimuli-responsive IONPs. This review will help provide guidance for designing IONPs as MRI CAs and further promote the reasonable design of magnetic nanoparticles and achieve early and accurate tumor detection.

Exploring the reciprocal relationship between activities of daily living disability and depressive symptoms among middle-aged and older Chinese people: a four-wave, cross-lagged model.

BACKGROUND: Early studies have shown a relationship between activities of daily living (ADL) disability and depressive symptoms in older people. However, discussions on the direction of this relationship are insufficient. The study's objective was to assess the reciprocal relationship between ADL disability and depressive symptoms among middle-aged and older Chinese people. METHOD: Data was collected in four waves of a nationwide survey, the China Health and Retirement Longitudinal Study (CHARLS), which was carried out in 2011, 2013, 2015, and 2018. In total, this study included 4,124 participants aged ≥ 45 years at baseline. A summing score of the eleven items for basic activities of daily living (BADL) and instrumental activities of daily living (IADL) was calculated to indicate the degree of ADL disability. The 10-item Centre for Epidemiological Studies Depression Scale (CESD-10) was adopted to measure depressive symptoms. The reciprocal relationship between ADL disability and depressive symptoms was tested by cross-lagged models. RESULT: At baseline, 911 (22.1%) participants were classified as having difficulties with ADL, and the prevalence of depressive symptoms was 34.4% (1,418). Among middle-aged and older people in China, there was a significant reciprocal and longitudinal relationship between ADL disability and depressive symptoms. People who had difficulty with ADL faced a higher risk of depressive symptoms, and those who suffered from depressive symptoms were accompanied by an increase in ADL disability in the following years. The subgroup analysis on age also showed that ADL disability was reciprocally and longitudinally related to depressive symptoms. However, only women showed similar results in the subgroup analysis on gender. CONCLUSION: This study shows that ADL disability is bi-directionally related to depressive symptoms in middle-aged and older Chinese people over time. The results suggest we should identify ADL disability and bad psychological conditions in time to prevent subsequent mutual damage among middle-aged and older Chinese people, a vulnerable group rising in the future.

SPRY4 inhibits and sensitizes the primary KIT mutants in gastrointestinal stromal tumors (GISTs) to imatinib.

BACKGROUND: KIT is frequently mutated in gastrointestinal stromal tumors (GISTs), and the treatment of GISTs largely relies on targeting KIT currently. In this study, we aimed to investigate the role of sprouty RTK signaling antagonist 4 (SPRY4) in GISTs and related mechanisms. METHODS: Ba/F3 cells and GIST-T1 cell were used as cell models, and mice carrying germline KIT/V558A mutation were used as animal model. Gene expression was examined by qRT-PCR and western blot. Protein association was examined by immunoprecipitation. RESULTS: Our study revealed that KIT increased the expression of SPRY4 in GISTs. SPRY4 was found to bind to both wild-type KIT and primary KIT mutants in GISTs, and inhibited KIT expression and activation, leading to decreased cell survival and proliferation mediated by KIT. We also observed that inhibition of SPRY4 expression in KITV558A/WT mice led to increased tumorigenesis of GISTs in vivo. Moreover, our results demonstrated that SPRY4 enhanced the inhibitory effect of imatinib on the activation of primary KIT mutants, as well as on cell proliferation and survival mediated by the primary KIT mutants. However, in contrast to this, SPRY4 did not affect the expression and activation of drug-resistant secondary KIT mutants, nor did it affect the sensitivity of secondary KIT mutants to imatinib. These findings suggested that secondary KIT mutants regulate a different downstream signaling cascade than primary KIT mutants. CONCLUSIONS: Our results suggested that SPRY4 acts as negative feedback of primary KIT mutants in GISTs by inhibiting KIT expression and activation. It can increase the sensitivity of primary KIT mutants to imatinib. In contrast, secondary KIT mutants are resistant to the inhibition of SPRY4.

[Features of Production Process and Risk Prevention and Control Points of Corona Virus Disease 2019 (2019-nCoV) Antigen Detection Reagent (Colloidal Gold Method)].

Corona Virus Disease 2019 (2019-nCoV) antigen detection reagent (colloidal gold method) has been applied to people who go to basic medical and health institutions for medical treatment and have respiratory tract, fever and other symptoms within 5 days, isolate observers, community residents who need antigen self-testing. The wide application of the reagent can effectively shorten the detection time, reduce the detection cost and time cost, and alleviate the pressure of nucleic acid detection. The article details the structural components, testing principles, production process and key risk points of the new coronavirus antigen test reagents, with the aim of providing a reference for the development of relevant work specifications for manufacturers, the organization of safe production and the verification and supervision of regulatory authorities.

Endothelial KCa3.1 and KCa2.3 Mediate S1P (Sphingosine-1-Phosphate)-Dependent Vasodilation and Blood Pressure Homeostasis.

BACKGROUND: S1P (sphingosine-1-phosphate) has been reported to possess vasodilatory properties, but the underlying pathways are largely unknown. METHODS: Isolated mouse mesenteric artery and endothelial cell models were used to determine S1P-induced vasodilation, intracellular calcium, membrane potentials, and calcium-activated potassium channels (KCa2.3 and KCa3.1 [endothelial small- and intermediate-conductance calcium-activated potassium channels]). Effect of deletion of endothelial S1PR1 (type 1 S1P receptor) on vasodilation and blood pressure was evaluated. RESULTS: Mesenteric arteries subjected to acute S1P stimulation displayed a dose-dependent vasodilation response, which was attenuated by blocking endothelial KCa2.3 or KCa3.1 channels. In cultured human umbilical vein endothelial cells, S1P stimulated immediate membrane potential hyperpolarization following activation of KCa2.3/KCa3.1 with elevated cytosolic Ca2+. Further, chronic S1P stimulation enhanced expression of KCa2.3 and KCa3.1 in human umbilical vein endothelial cells in dose- and time-dependent manners, which was abolished by disrupting either S1PR1-Ca2+ signaling or downstream Ca2+-activated calcineurin/NFAT (nuclear factor of activated T-cells) signaling. By combination of bioinformatics-based binding site prediction and chromatin immunoprecipitation assay, we revealed in human umbilical vein endothelial cells that chronic activation of S1P/S1PR1 promoted NFATc2 nuclear translocation and binding to promoter regions of KCa2.3 and KCa3.1 genes thus to upregulate transcription of these channels. Deletion of endothelial S1PR1 reduced expression of KCa2.3 and KCa3.1 in mesenteric arteries and exacerbated hypertension in mice with angiotensin II infusion. CONCLUSIONS: This study provides evidence for the mechanistic role of KCa2.3/KCa3.1-activated endothelium-dependent hyperpolarization in vasodilation and blood pressure homeostasis in response to S1P. This mechanistic demonstration would facilitate the development of new therapies for cardiovascular diseases associated with hypertension.