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Lithospheric structure beneath the northeastern Qinghai-Xizang Plateau is of vital significance for studying the geodynamic processes of crustal thickening and expansion of the Qinghai-Xizang Plateau. We conducted a joint inversion of receiver functions and surface wave dispersions with P-wave velocity constraints using data from the ChinArray II temporary stations deployed across the Qinghai-Xizang Plateau. Prior to joint inversion, we applied the H-κ-c method (Li JT et al., 2019) to the receiver function data in order to correct for the back-azimuthal variations in the arrival times of Ps phases and crustal multiples caused by crustal anisotropy and dipping interfaces. High-resolution images of vS, crustal thickness, and vP/vS structures in the Qinghai-Xizang Plateau were simultaneously derived from the joint inversion. The seismic images reveal that crustal thickness decreases outward from the Qinghai-Xizang Plateau. The stable interiors of the Ordos and Alxa blocks exhibited higher velocities and lower crustal vP/vS ratios. While, lower velocities and higher vP/vS ratios were observed beneath the Qilian Orogen and Songpan-Ganzi terrane (SPGZ), which are geologically active and mechanically weak, especially in the mid-lower crust. Delamination or thermal erosion of the lithosphere triggered by hot asthenospheric flow contributes to the observed uppermost mantle low-velocity zones (LVZs) in the SPGZ. The crustal thickness, vS, and vP/vS ratios suggest that whole lithospheric shortening is a plausible mechanism for crustal thickening in the Qinghai-Xizang Plateau, supporting the idea of coupled lithospheric-scale deformation in this region.

Disorders of the central nervous system (CNS) constitute a significant global health concern at the moment. Most CNS disorders are characterized by severe neuronal damage with excessive production of reactive oxygen species, which induces high levels of oxidative stress and intense inflammatory responses in the affected tissues, thus aggravating disease pathology. Notably, the blood–brain barrier makes it difficult to deliver many drugs and biologics to the CNS, which creates great difficulties in the diagnosis and treatment of CNS disorders. Recent research on polydopamine nanotechnology has led to the discovery of many promising properties; it shows strong scavenging ability for reactive oxygen species, prevents activation of pro-inflammatory microglia, and its repair function can reduce brain damage and protect neurons. Moreover, polydopamine nanotechnology can improve the blood–brain barrier permeability of biologics and reduce their neurotoxicity. It is therefore a promising candidate in the treatment of CNS disorders associated with oxidative stress. In the present paper, we review the functionality of polydopamine nanotechnology as well as the potential and recent advances of polydopamine-based nanosystems in the diagnosis and treatment of various CNS disorders, including Alzheimer’s disease, Parkinson’s disease, stroke, spinal cord injury, and glioma. Finally, we predict how polydopamine nanoparticles may guide future therapeutic strategies to address CNS disorders such as epilepsy, which currently have no cure.

Abstract Background Moderate caffeine intake decreases the risk of metabolic disorders and all-cause mortality, and the mechanism may be related to its ergogenic actions. Thyroid hormones are vital in metabolic homeostasis; however, their association with caffeine intake has rarely been explored. Objective To investigate the association between caffeine intake and thyroid function. Methods We collected data on demographic background, medical conditions, dietary intake, and thyroid function from the National Health and Nutrition Examination Survey (NHANES) 2007–2012. Subgroups were classified using two-step cluster analysis, with sex, age, body mass index (BMI), hyperglycemia, hypertension, and cardio-cerebral vascular disease (CVD) being used for clustering. Restrictive cubic spline analysis was employed to investigate potential nonlinear correlations, and multivariable linear regression was used to evaluate the association between caffeine consumption and thyroid function. Results A total of 2,582 participants were included, and three subgroups with different metabolic features were clustered. In the most metabolically unhealthy group, with the oldest age, highest BMI, and more cases of hypertension, hyperglycemia, and CVD, there was a nonlinear relationship between caffeine intake and serum thyroid stimulating hormone (TSH) level. After adjusting for age, sex, race, drinking, smoking, medical conditions, and micronutrient and macronutrient intake, caffeine intake of less than 9.97 mg/d was positively associated with serum TSH (p = 0.035, standardized β = 0.155); however, moderate caffeine consumption (9.97–264.97 mg/d) indicated a negative association (p = 0.001, standardized β = − 0.152). Conclusions Caffeine consumption had a nonlinear relationship with serum TSH in people with metabolic disorders, and moderate caffeine intake (9.97 ~ 264.97 mg/d) was positively associated with serum TSH.

Transmissible gastroenteritis virus (TGEV) could cause diarrhea, vomiting, dehydration and even death in piglets, miRNA played an important role in the interaction between virus and cell. The study aimed to investigate the impact of miR-17 on the polysaccharide of Polygonum Cillinerve (PCP) in combating TGEV. miR-17 was screened and transfection validation was performed by Real-time PCR. The function of miR-17 on PK15 cells infected with TGEV and treated with PCP was investigated by DCFH-DA loading probe, JC-1 staining and Hoechst fluorescence staining. Furthermore, the effect of miR-17 on PCP inhibiting TGEV replication and apoptosis signaling pathways during PCP against TGEV infection was measured through Real-time PCR and Western blot. The results showed that miR-17 mimic and inhibitor could be transferred into PK15 cells and the expression of miR-17 significantly increased and decreased respectively compared with miR-17 mimic and inhibitor (P < 0.05). A total 250 μg/mL of PCP could inhibit cells apoptosis after transfection with miR-17. PCP (250 μg/mL and 125 μg/mL) significantly inhibited the decrease in mitochondrial membrane potential induced by TGEV after transfection with miR-17 (P < 0.05). After transfection of miR-17 mimic, PCP at concentrations of 250 μg/mL and 125 μg/mL significantly promoted the mRNA expression of P53, cyt C and caspase 9 (P < 0.05). Compared with the control group, the replication of TGEV gRNA and gene N was significantly inhibited by PCP at concentrations of 250 μg/mL and 125 μg/mL after transfection of both miR-17 mimic and inhibitor (P < 0.05). PCP at 62.5 μg/mL significantly inhibited the replication of gene S following transfection with miR-17 inhibitor (P < 0.05). These results suggested that PCP could inhibit the replication of TGEV and apoptosis induced by TGEV by regulating miR-17.

Background: Preconditioning is a promising strategy against ischemic brain injury, and numerous studies in vitro and in vivo have demonstrated its neuroprotective effects. However, at present there is no bibliometric analysis of preconditioning in cerebral ischemia. Therefore, a comprehensive overview of the current status, hot spots, and emerging trends in this research field is necessary. Materials and methods: Studies on preconditioning in cerebral ischemia from January 1999–December 2022 were retrieved from the Web of Science Core Collection (WOSCC) database. CiteSpace was used for data mining and visual analysis. Results: A total of 1738 papers on preconditioning in cerebral ischemia were included in the study. The annual publications showed an upwards and then downwards trend but currently remain high in terms of annual publications. The US was the leading country, followed by China, the most active country in recent years. Capital Medical University published the largest number of articles. Perez-Pinzon, Miguel A contributed the most publications, while KITAGAWA K was the most cited author. The focus of the study covered three areas: (1) relevant diseases and experimental models, (2) types of preconditioning and stimuli, and (3) mechanisms of ischemic tolerance. Remote ischemic preconditioning, preconditioning of mesenchymal stem cells (MSCs), and inflammation are the frontiers of research in this field. Conclusion: Our study provides a visual and scientific overview of research on preconditioning in cerebral ischemia, providing valuable information and new directions for researchers.

Ethnopharmacological relevance: Fructus mume herbs have been used to convergence and antidiarrheal in clinical practice in China for thousands of years. Aim of the study: This study aimed to investigate the molecular mechanism of Fructus mume in the treatment of UC through network pharmacology analysis and experimental validation in vivo. Materials and methods: The main components of Fructus mume were initially identified with the aid of liquid chromatography-mass spectrometry. Using the network pharmacology approach, we predicted the targets of the active components and mapped target genes related to UC. We further evaluated the pharmacodynamic effects of Fructus mume on UC in vivo using a DSS-induced mousemodel of colitis. The degree of pathological damage in mousecolon tissue was examined via hematoxylin-eosin (HE) staining. The results of network pharmacology predictions were further verified measuring the levels of inflammatory and oxidation-related factors in mouse colon tissue via enzyme linked immunosorbent assay method and Western blot analysis. Results: A total of 16 chemical components of Fructus mume were identified, among which 11 active components were screened based on the Ribinski rule and 368 targets predicted. KEGG pathway analysis showed that the predicted targets involved multiple signaling pathways, including PI3K-Akt, AGE-RAGE and HIF-1. In pharmacodynamic experiments, Fructus mume induced a significant increase in colon length and improved the degree of damage to colon tissue. In addition, FM inhibited the increase in TNF-α, IL-1β, NADPH and ROS levels in sera of UC mice, thereby suppressing the occurrence and development of UC. At higher concentrations, Fructus mume inhibited protein expression of downstream related (p38, p-p38, NF-kB and p-NF-kB) through regulation of the AGE/RAGE pathway, further contributing to suppression of UC in mice. Conclusion: Our experiments provide important insights into the pharmacological basis of Fructus mume and its potential multicomponent-multitarget-multipathway pharmacological activities against UC. The therapeutic mechanism of Fructus mume may be associated with suppression of protein expression, p38, p-p38, NF-kB and p-NF-kB, in the AGE/RAGE pathway, partially validating the results from network pharmacology analysis. The collective findings provide a theoretical basis for the further development and clinical application of Fructus mume.

BackgroundDue to environmental pollution, changes in lifestyle, and advancements in diagnostic technology, the prevalence of asthma has been increasing over the years. Although China has made early efforts in asthma epidemiology and prevention, there is still a lack of unified and comprehensive epidemiological research within the country. The objective of the study is to determine the nationwide prevalence distribution of asthma using the Baidu Index and China's Health Statistical Yearbook.MethodsBased on China's Health Statistical Yearbook, we analyzed the gender and age distribution of asthma in China from 2011 to 2020, as well as the length of hospitalization and associated costs. By utilizing the Baidu Index and setting the covering all 31 provinces and autonomous regions in China, we obtained the Baidu Index for the keyword 'asthma'. Heatmaps and growth ratios described the prevalence and growth of asthma in mainland China.ResultsThe average expenditure for discharged asthma (standard deviation) patients was ¥5,870 (808). The average length of stay (standard deviation) was 7.9 (0.38) days. During the period of 2011 to 2020, hospitalization expenses for asthma increased while the length of hospital stay decreased. The proportion of discharged patients who were children under the age of 5 were 25.3% (2011), 19.4% (2012), 16% (2013), 17.9% (2014), 13.9% (2015), 11.3% (2016), 10.2% (2017), 9.4% (2018), 8.1% (2019), and 7.2% (2020), respectively. The prevalence of asthma among boys was higher than girls before the age of 14. In contrast, the proportion of women with asthma was larger than men after the age of 14. During the period from 2011 to 2020, the median [The first quartile (Q1)-the third quartile (Q3)] daily asthma Baidu index in Guangdong, Beijing, Jiangsu, Sichuan, and Zhejiang were 419 (279–476), 328 (258–376), 315 (227–365), 272 (166–313), and 312 (233–362) respectively. Coastal regions showed higher levels of attention toward asthma, indicating a higher incidence rate. Since 2014, there has been a rapid increase in the level of attention toward asthma, with the provinces of Qinghai, Sichuan, and Guangdong experiencing the fastest growth.ConclusionThere are regional variations in the prevalence of asthma among different provinces in China, and the overall prevalence of asthma is increasing.

Studies have shown that inhibition of PI3K/AKT signaling is a key strategy for the treatment of tyrosine kinase inhibitor resistance in non-small cell lung cancer (NSCLC). Vasculogenic mimicry (VM) not only accelerates tumor progression but also increases drug-induced resistance. As a tumor suppressor, protein phosphatase 2A (PP2A) is a ubiquitous conserved serine/threonine phosphatase. While its effects and mechanisms on VM formation and invasion in NSCLC remain unclear. The present study aimed to investigate the role of PP2A in VM formation and elucidate the underlying mechanisms. Results showed that PP2A could significantly inhibit VM formation and VM-dependent behavior, including invasion and migration both in vitro and in vivo. Activation of PP2A with FTY720 or Ad-PP2A reduced phosphorylated AKT and inhibited ZEB1 transcription, thereby further downregulating the expression of MMP-2, VE-cadherin, and VEGFR-2, whereas inhibition of PP2A with okadaic acid (OA) or Ad-dn-PP2A exerted the opposite effect. Furthermore, PP2A inhibited tumor growth and VM formation in the xenograft tumor model. PI3K inhibitor BENC-511 could potentiate activation of PP2A, leading to inhibition of p-AKT/ZEB1 and VM formation in vitro and in vivo. This study indicated that PP2A could regulate VM formation in NSCLC through the PI3K/AKT/ZEB1 axis. PP2A reactivation or combination with PI3K inhibitor might be a more effective treatment against advanced NSCLC by inhibiting VM formation.

With the widespread adoption of cloud computing, the face verification process often requires the client to upload the face to an untrusted cloud server to obtain the verification results. Privacy leakage issues may arise if the client’s private information is not protected. This paper proposes a secure and anonymous face verification scheme using fully homomorphic encryption technology and SealPIR. Our scheme is a three-party solution that requires a third-party server trusted by the client. This scheme not only prevents the client’s facial data from being obtained by untrusted data servers but also prevents the data server from learning the index corresponding to the face that the client wants to verify. In a single-face verification process, the client only needs to perform one upload operation and one download operation, with a communication volume of 264 KB. We can complete a privacy-protected anonymous face verification process in 84.91 ms.

With the improvement of building technical requirements and the updating of standards, the demand for the reinforcement of existing buildings is increasing. In order to solve the problem regarding the low economic applicability of the traditional seismic retrofit method, this paper proposes a seismic retrofit method for an externally attached U-shaped steel plate sub-structure that follows the concept of “reinforcing while using”, is composed of a U-shaped steel plate and herringbone channel steel, and can meet the needs of multiple retrofits. Based on the results of a pseudo-static test, the mechanical properties of one unreinforced frame and three reinforced frames with different specifications for the U-shaped steel plate sub-structure were comparatively studied, and the effectiveness and rationality of the reinforcement method were analyzed. The results show that the externally attached U-shaped steel plate sub-structure has good deformation and energy dissipation capacity and can effectively improve the horizontal bearing capacity of an existing frame without changing the original failure mode. The bearing capacity of the three reinforced frames was 1.43, 1.89, and 2.57 times that of the unreinforced specimen. The initial lateral stiffness of the frame also increased significantly, namely, to 1.41, 2.02, and 2.08 times that of the unreinforced specimen, and the stiffness degradation rate decreased. The seismic performance of the original frame was greatly improved.

Objectives The aims of the study were to assess the management of low-density lipoprotein cholesterol (LDL-C) and the goal achievement, as well as to investigate the association between baseline LDL-C level, lipid-lowering treatment (LLT), and stroke recurrence in patients with ischaemic stroke or transient ischaemic attack (TIA).Design Our study was a post hoc analysis of the Third China National Stroke Registry (CNSR-III).Setting We derived data from the CNSR-III - a nationwide clinical registry of ischaemic stroke and TIA based on 201 participating hospitals in mainland China.Participants 15,166 patients were included in this study with demographic characteristics, etiology, imaging, and biological markers from August 2015 to March 2018.Primary and secondary outcome measures The primary outcome was a new stroke, LDL-C goal (LDL-C

BackgroundIt is reported that insulin resistance widely exists in non-diabetic patients with a recent history of transient ischemic attack (TIA) or ischemic stroke. There is currently strong evidence to prove the bidirectional effect of glucose metabolism disorders and stroke events. Therefore, it is necessary to retrospectively tease out the current status, hotspots, and frontiers of insulin resistance and ischemic cerebrovascular disease through CiteSpace.Materials and methodsWe searched the Web of Science (WOS) for studies related to insulin resistance and ischemic cerebrovascular disease from 1999 to April 2022, then downloaded the data into CiteSpace to generate a knowledge visualization map.ResultsA total of 1,500 publications relevant to insulin resistance and ischemic cerebrovascular disease were retrieved. The USA had the most articles on this topic, followed by PEOPLES R CHINA and JAPAN. WALTER N KERNAN was the most prolific author, whose research mainly focused on insulin resistance intervention after stroke (IRIS) trial. The most common keywords were myocardial ischemia, metabolic syndrome, ischemic stroke, cerebral ischemia, association, oxidative stress, inflammation, and adipose tissue. Major ongoing research trends include three aspects: (1) the association between insulin resistance and ischemic cerebrovascular disease in non-diabetic patients, (2) the intrinsic pathological mechanism between insulin resistance and ischemic cerebrovascular disease, and (3) early intervention of insulin resistance to improve the prognosis of stroke.ConclusionThe results of this bibliometric study provide the current status and trends of clinical research publications in the field of insulin resistance and ischemic cerebrovascular disease. Insulin resistance is strongly associated with the occurrence of ischemic stroke, early neurological deterioration in stroke patients, post-stroke depression, and cerebral small vessel disease. Early treatment of insulin resistance can be an effective way to prevent the onset of ischemic stroke and improve stroke prognosis. This study may help researchers to identify hot topics and explore new research directions.

To examine the macro-and meso-mechanical behaviors and crack propagation mode of the prefabricated and fractured rock sample under biaxial compression, the particle flow code (PFC) is first used to study the effect of the micro-parameters of the parallel bond model on the macro-parameters. Combined with the conventional triaxial compression test of intact granite, the meso-parameters are calibrated. The mechanical properties of the sample with prefabricated double fractures (upper fracture ① and lower fracture ②) under confining pressure are simulated with the set of parameters. The results show that the PFC code and the calibrated parameters can better simulate the failure of the complete samples. As the confining pressure increases, the peak strength and elastic modulus of the double-fractured rock sample increase. When the angle α2 between the lower fracture ② and the horizontal is 90°, both of them reach the maximum values. Under different α2, the simulated crack evolution of each rock sample goes through three stages of crack initiation, development and stabilization. With the decreasing confining pressure and the increasing axial stress, the damage of the force chains between particles becomes more severe. Due to the difference in the concentration and distribution of the tensile force chains, the cracks along the length of the horizontal fracture propagate along the axial direction, and the penetration of the two fractures presents different ways.

BackgroundCurrently, there is little literature about the association between physical activity (PA) and the risk of ankylosing spondylitis (AS). The present study aimed to understand the causal relationships between PA and AS.MethodsWe performed two-sample Mendelian randomization (MR) using publicly released genome-wide association studies summary statistics to estimate the causal associations of PA with AS risk. The inverse variance weighted (IVW) method was utilized as primary MR analysis. Furthermore, sensitivity, pleiotropy, and heterogeneity analyses were then conducted to assess the robustness of the findings of the present study.ResultsResults of the IVW analysis suggested a protective relationship between accelerometer-based PA and AS (average acceleration, odds ratio [OR] = 0.9995, 95% CI, 0.9988–0.9999, P = 0.014). On the contrary, there was no causal relationship between accelerometer-based PA (acceleration fraction >425 mg; OR = 0.9981, 95% CI = 0.9936–1.0026, P = 0.402) and AS. Furthermore, there was no significant relationship between self-reported vigorous PA and AS (OR = 1.0005, 95% CI = 0.9875–1.0136, P = 0.943), or even between self-reported moderate-to-vigorous PA and AS (OR = 1.0000, 95% CI, 0.9947–1.0052; P = 0.990).ConclusionsThe use of genetic approach in the present study revealed that total physical activity (TPA) has a protective relationship with AS risk. Furthermore, it was evident that vigorous PA or moderate-to-vigorous physical levels are not causally associated with AS. Therefore, the present study evidently supports the hypothesis that enhancing TPA rather than PA intensity is an effective prevention strategy for AS.

BackgroundEarly prediction and classification of prognosis is essential for patients in the coronary care unit (CCU). We applied a machine learning (ML) model using the eXtreme Gradient Boosting (XGBoost) algorithm to prognosticate CCU patients and compared XGBoost with traditional classification models.MethodsCCU patients' data were extracted from the MIMIC-III v1.4 clinical database, and divided into four groups based on the time to death:

BackgroundHeart failure (HF), primarily caused by conditions such as coronary heart disease or cardiomyopathy, is a global health problem with poor prognosis and heavy burden on healthcare systems. As biomarkers of myocardial injury and fibrosis, suppression of tumorigenicity 2 (ST2) and galectin-3 were recommended for prognosis stratification in HF guidelines. However, the causality between these two mediators and HF remains obscure. This study aimed to explore the causal relationship of genetically determined ST2 and galectin-3 with the risk of HF.MethodsWe used the two-sample Mendelian randomization (MR) method, incorporating available genome-wide association summary statistics, to investigate the causal association of ST2 and galectin-3 with HF risk. We applied inverse-variance weighted analysis as the main method of analysis.ResultsIn our final MR analysis, 4 single-nucleotide polymorphisms (SNPs) of ST2 and galectin-3, respectively, were identified as valid instrumental variables. Fixed-effect inverse variance weighted (IVW) analysis indicated that genetically predicted ST2 and galectin-3 were not causally associated with HF risk 3. [odds ratio (OR) = 0.9999, 95% confidence interval [CI] = 0.9994–1.0004, p = 0.73; OR = 1.0002, 95% CI = 0.9994–1.0010, p = 0.60, respectively]. These findings were robust in sensitivity analyses, including MR-Egger regression and leave-one-out analysis.ConclusionThis MR study provided no evidence for the causal effects of ST2 and galectin-3 on HF risk.

Background Small single subcortical infarction (SSSI) may be classified as parent artery disease-related or only branch involved according to the stenosis of parent artery. The study aimed to evaluate short-term and long-term prognoses and the effectiveness of antiplatelet therapy in SSSI.Methods We prospectively enrolled 2890 patients with SSSI from the Third China National Stroke Registry (CNSR-III) database from August 2015 to March 2018. We assessed clinical outcomes and antiplatelet treatment effects in patients with SSSI with and without parent artery stenosis (PAS) identified by magnetic resonance angiography.Results Among 2890 patients with SSSI in the perforator territory of the middle cerebral artery and the basilar artery, there were 680 (23.53%) patients with PAS and 2210 (76.47%) patients without PAS, respectively. After adjusting for potential confounders, the PAS group had a greater initial stroke severity (OR 1.262, 95% CI 1.058 to 1.505; p=0.0097) and a higher risk of ischaemic stroke recurrence at 3 months (OR 2.266, 95% CI 1.631 to 3.149; p

The ecological functions and biogeochemical processes of continental marginal seas are important for the global carbon cycle. In the eastern China marginal seas (ECMS), phytoplankton productivity has increased significantly in recent decades, but the sources and burial processes of marine organic carbon (OC) remain under-studied. We analyzed the contents of marine lipid biomarkers (brassicasterol, dinosterol, and C37 alkenones) in surface suspended particles obtained from seven cruises between 2010 and 2015, and in surface sediments from eight cruises between 2006 and 2012 in the ECMS, to estimate marine OC sources and burial. The correlations between lipid biomarkers and environmental factors were quantified to reveal controlling factors. The study area was divided into four regions according to cluster analysis conducted based on sediment parameters. Our results showed that the concentrations of marine lipid biomarkers in surface water were high near large estuaries such as the Changjiang River Estuary and the Yellow River Estuary, but those in surface sediments were high in mud areas. Nutrient concentration was a key factor controlling phytoplankton biomass in surface water, with high nutrients enhancing the growth of diatoms and dinoflagellates, while haptophytes were more abundant in low-nutrient, high-salinity and cold environments. High marine OC contents calculated from total OC δ13C were mainly associated with fine sediments transported by coastal currents, and finally deposited in mud areas. The proto-burial efficiency of marine OC in the ECMS (7–19%) was markedly higher than the mean value in global marginal seas, with high values being located in the western coast of the ECMS. The proto-burial efficiency of total marine lipid biomarkers (6–24%) was quantified for the first time in our study, with overall values and spatial patterns similar to that of marine OC. A key parameter for marine OC and marine biomarker proto-burial efficiency was sediment grain size. The smaller the sediment grain size was, the better the marine OC and marine biomarker were retained. Our study provides an important basis to elucidate spatial distribution patterns and forcing mechanisms of marine OC in surface water (production process) and surface sediments (burial process), and to estimate carbon budgets in large marginal seas.

Background: Generalized anxiety disorder (GAD) is one of the most common types of anxiety disorders with unclear pathogenesis. Our team’s previous research found that extensive neuronal apoptosis and neuronal regeneration disorders occur in the hippocampus of GAD rats. Danzhi Xiaoyao (DZXYS) Powder can improve the anxiety behavior of rats, but its molecular mechanism is not well understood.Objective: This paper discusses whether the pathogenesis of GAD is related to the abnormal expression of Notch signal pathway, and whether the anti-anxiety effect of DZXYS promotes nerve regeneration in the hippocampus by regulating the Notch signaling pathway.Methods: The animal model of GAD was developed by the chronic restraint stress and uncertain empty bottle stimulation method. After the model was successfully established, the rats in the model preparation group were divided into the buspirone, DZXYS, DZXYS + DAPT, and model groups, and were administered the corresponding drug intervention. The changes in body weight and food intake of rats were continuously monitored throughout the process. The changes in anxiety behavior of rats were measured by open field experiment and elevated plus-maze test, and morphological changes and regeneration of neurons in the rat hippocampus were observed by HE staining and double immunofluorescence staining. Changes in the expression of key targets of the Notch signaling pathway in the hippocampus were monitored by real-time fluorescence quantitative PCR and western blotting.Results: In this study, we verified that the GAD model was stable and reliable, and found that the key targets of the Notch signaling pathway (Notch1, Hes1, Hes5, etc.) in the hippocampus of GAD rats were significantly upregulated, leading to the increased proliferation of neural stem cells in the hippocampus and increased differentiation into astrocytes, resulting in neuronal regeneration. DZXYS intervention in GAD rats can improve appetite, promote weight growth, and significantly reverse the anxiety behavior of GAD rats, which can inhibit the upregulation of key targets of the Notch signaling pathway, promote the differentiation of neural stem cells in the hippocampus into neurons, and inhibit their differentiation into astrocytes, thus alleviating anxiety behavior.Conclusion: The occurrence of GAD is closely related to the upregulation of the Notch signaling pathway, which hinders the regeneration of normal neurons in the hippocampus, while DZXYS can downregulate the Notch signaling pathway and promote neuronal regeneration in the hippocampus, thereby relieving anxiety behavior.

The Permanently Shadowed Regions (PSRs) of the lunar south pole have never been directly sampled. To explore and discover lunar resources, the Chinese lunar south pole exploration mission is scheduled to land in direct sunlight near the PSR, where sampling and analysis will be carried out. The selection of sites for lunar landing sampling sites is one of the key steps of the mission. The main factors affecting the site selection are the distribution of PSRs, lunar surface slopes, rock distribution, light intensity, and maximum temperature. In this paper, the main factors affecting site selection are analyzed based on lunar multi-source remote sensing data. Combined with previous engineering constraints, we then propose a comprehensive multi-factor fuzzy cognition and selection model for the lunar south site selection. An analytical model based on a fuzzy cognitive map algorithm is also established. Furthermore, to make a preliminary landing area selection, we determine the evaluation index for the candidate landing areas using fuzzy reasoning. Using the proposed model and combined scoring index, we also verify and analyze the prominent impact craters at the lunar south pole. The scores of de Gerlache (88.48°S 88.34°W), Shackleton (89.67°S 129.78°E), and Amundsen (84.5°S, 82.8°E) craters are determined using fuzzy interference as 0.816, 0.814, and 0.784, respectively. Moreover, using our proposed approach, we identify feasible landing sites around the de Gerlache crater close to the PSR to facilitate discovery of water ice exposures in future missions. The proposed method is capable of evaluating alternative landing zones subject to multiple engineering constraints on the Moon or Mars based on the existing data.

Accentuated Cut Edges (ACE) is a recently developed grape must extraction technique, which mechanically breaks grape skins into small fragments but maintains seed integrity. This study was the first to elucidate the effect of ACE on Shiraz wine’s basic chemical composition, colour, phenolic compounds, polysaccharides and sensory profiles. A further aim was to investigate any potential influence provided by ACE on the pre-fermentation water addition to must. ACE did not visually affect Shiraz wine colour, but significantly enhanced the concentration of tannin and total phenolics. Wine polysaccharide concentration was mainly increased in response to the maceration time rather than the ACE technique. ACE appeared to increase the earthy/dusty flavour, possibly due to the different precursors released by the greater skin breakage. The pre-fermentation addition of the water diluted the wine aromas, flavours and astringency profiles. However, combining the ACE technique with water addition enhanced the wine textural quality by increasing the intensities of the crucial astringent wine quality sub-qualities, adhesive and graininess. Furthermore, insights into the chemical factors influencing the astringency sensations were provided in this study. This research indicates that wine producers may use ACE with pre-fermentation water dilution to reduce the wine alcohol level but maintain important textural components.

Data box is the basic data unit opened to the data users in self-governing openness of data,so the prevention for the degradation of data scarcity and the disclosure of privacy is mainly aimed at the data box.A data box may contain photos,videos,text and structured data,etc.The traditional data encryption technology cannot be effectively applied.The requirement of data encryption for data box and the challenges of traditional data encryption technologies were analyzed,and the prospect of new encryption technologies for self-governing openness of data was discussed.

The P-to-S converted phase at the Moho (the Pms phase) contains important information regarding the crustal structure. Here, we employ a grid search approach to simultaneously extract the bulk crustal azimuthal anisotropy and Moho orientation using receiver functions. The solution of this approach is the weighted average of two individual subfunctions that separately analyze the birefringence and arrival time of the Pms phase. Since a tilted Moho deflects the polarized components of the Pms phase, the Pms birefringence subfunction minimizes the energy on all the transverse polarization components (i.e., the transverse polarization direction before Pms splitting). The implementation of this subfunction is similar to that of the transverse component minimization method, but the Moho orientation is considered. The Pms arrival time subfunction takes into account both the crustal anisotropy and the Moho orientation to predict and fit Pms arrivals. According to extensive synthetic experiments, this approach is remarkably robust to the presence of strong anisotropy, a steep Moho, and slightly tilted fast axes (less than 30°). This approach is also highly tolerant of random noise and data with uneven azimuthal coverage. We apply this approach to three permanent stations on the Tibetan Plateau. The resulting measurements boast a high quality and are consistent with the crustal anisotropy and Moho orientation revealed in previous studies. [ABSTRACT FROM AUTHOR]

Context: Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) play an indispensable role in the treatment of non‑small cell lung cancer (NSCLC), leading to a survival major breakthrough, but there remains no uniform standard for predicting the efficacy of TKI therapy. Aims: We retrospectively reviewed the use of EGFR‑TKIs for advanced NSCLC between January 2009 and December 2017 in a hospital, which 169 patients who treated with first‑line TKIs were enrolled. Subjects and Methods: Multiple clinical factors, including histology, age, and sex, were analyzed. We calculated the tumor shrinkage rate (TSR) by measuring the longest diameters of the main mass by computed tomography (CT) before TKI therapy and the first CT after TKI therapy. We evaluated overall survival (OS) and progression‑free survival (PFS) after first‑line TKI therapy, and we assessed factors predicting survival using the Kaplan–Meier method. Results: Eligible patients were sorted into higher (n = 83) and lower (n = 86) TSR groups according to the mean TSR of 0.49%. The 83 patients with a higher TSR had longer PFS and OS than those in the 86 patients with a lower TSR (14.83 vs. 8.40 months, P < 0.001, and 31.03 vs. 20.10 months, P < 0.001, respectively). Multivariate analyses revealed that TSR was an independent predictor of PFS and OS (PFS hazard ratio [HR]: 0.506, P < 0.001, and OS HR: 0.291, P < 0.001). Conclusions: These cumulative data support that TSR may be an early predictor of the treatment efficacy in NSCLC with EGFR mutations treated with first‑line TKIs. [ABSTRACT FROM AUTHOR]

In the present study, we aimed to prepare Panax japonicus tablets and carry out quality inspection. Panax japonicus tablets were prepared by ultrafine pulverization-wet granulation, and quality inspection was carried out according to Pharmacopoeia regulations. The plasma concentration of animals with self-made Panax japonicus tablets or ginsenoside Rg3 in single-dose intragastric administration was determined by high-performance liquid chromatography (HPLC). The pharmacokinetic parameters and relative bioavailability were calculated by DAS 2.0 software. The quality inspection of self-made Panax japonicus tablets met the requirements of Chinese Pharmacopoeia (2015 edition), and this preparation had high bioequivalence of ginsenoside Rg3. The preparation of Panax japonicus tablets was reasonable and highly qualified. Moreover, this new Panax japonicus preparation showed better profiles in oral absorption and utilization. This study provided evidence for the industrial production and clinical application of Panax japonicus tablets. [ABSTRACT FROM AUTHOR]

Background Diabetes and osteoporosis are common diseases in middle-aged and elderly people. Diabetes can lead to various acute and chronic complications, but its related bone changes are often neglected. Osteoporosis is more common in postmenopausal women, and those with type 2 diabetes mellitus (T2DM) have multiple risk factors for osteoporosis. Therefore, it is particularly important to early identify risk factors of osteoporosis in these women, and to provide them with targeted interventions. Objective To explore the associated factors of osteoporosis in Chinese postmenopausal women with T2DM through a meta-analysis. Methods In July 2021, databases of China National Knowledge Infrastructure, CQVIP, WanFang Data, SinoMed, PubMed, EmBase, and the Cochrane Library were searched for literature about factors associated with osteoporosis in Chinese postmenopausal women with T2DM from inception to July 2021. Two researchers independently screened literature and extracted data. RevMan 5.4 and Stata 15.0 were used to conduct a meta-analysis on the data. Results Twenty-one studies were finally included, from which 11 osteoporosis-related factors were extracted. The meta-analysis showed that age〔MD (95%CI) =6.56 (5.24, 7.88) 〕, years of postmenopause〔MD (95%CI) =5.93 (4.23, 7.62) 〕, duration of diabetes〔MD (95%CI) =1.94 (0.89, 2.98) 〕, body mass index〔MD (95%CI) =-1.99 (-2.63, -1.36) 〕, serum calcium〔MD (95%CI) =0.03 (0.01, 0.06) 〕, fasting blood glucose〔MD (95%CI) =0.49 (0.09, 0.90) 〕, glycosylated hemoglobin〔MD (95%CI) =0.37 (0.02, 0.71) 〕, and fasting insulin〔MD (95%CI) =3.65 (1.24, 6.06) 〕 were associated factors for osteoporosis in postmenopausal women with T2DM. But no significant association was found between osteoporosis and serum creatinine〔MD (95%CI) =4.02 (0.00, 8.04) 〕, serum phosphorus〔MD (95%CI) =0.00 (-0.05, 0.05) 〕, or serum alkaline phosphatase〔MD (95%CI) =1.26 (-0.06, 2.57) 〕 in these women. Sensitivity analysis revealed that the association of all the above-mentioned factors (except for serum creatinine) with osteoporosis was relatively robust. Conclusion Older age, long years of postmenopause, long duration of T2DM, low levels of BMI and serum calcium, and high levels of fasting insulin, fasting blood glucose, and glycosylated hemoglobin are risk factors for osteoporosis in Chinese postmenopausal women with T2DM. But the effects of serum creatinine, phosphorus, and alkaline phosphatase on osteoporosis in this group need to be further verified.