Search

Gastrodin (GAS) is the main chemical component of the traditional Chinese herb Gastrodia elata (called “Tianma” in Chinese), which has been used to treat neurological conditions, including headaches, epilepsy, stroke, and memory loss. To our knowledge, it is unclear whether GAS has a therapeutic effect on Huntington’s disease (HD). In the present study, we evaluated the effect of GAS on the degradation of mutant huntingtin protein (mHtt) by using PC12 cells transfected with N-terminal mHtt Q74. We found that 0.1–100 μM GAS had no effect on the survival rate of Q23 and Q74 PC12 cells after 24–48 h of incubation. The ubiquitin–proteasome system (UPS) is the main system that clears misfolded proteins in eukaryotic cells. Mutated Htt significantly upregulated total ubiquitinated protein (Ub) expression, decreased chymotrypsin-like, trypsin-like and caspase-like peptidase activity, and reduced the colocalization of the 20S proteasome with mHtt. GAS (25 μM) attenuated all of the abovementioned pathological changes, and the regulatory effect of GAS on mHtt was found to be abolished by MG132, a proteasome inhibitor. The autophagy–lysosome pathway (ALP) is another system for misfolded protein degradation. Although GAS downregulated the expression of autophagy markers (LC3II and P62), it increased the colocalization of LC3II with lysosomal associated membrane protein 1 (LAMP1), which indicates that ALP was activated. Moreover, GAS prevented mHtt-induced neuronal damage in PC12 cells. GAS has a selective effect on mHtt in Q74 PC12 cells and has no effect on Q23 and proteins encoded by other genes containing long CAGs, such as Rbm33 (10 CAG repeats) and Hcn1 (>30 CAG repeats). Furthermore, oral administration of 100 mg/kg GAS increased grip strength and attenuated mHtt aggregates in B6-hHTT130-N transgenic mice. This is a high dose (100 mg/kg GAS) when compared with experiments on HD mice with other small molecules. We will design more doses to evaluate the dose–response relationship of the inhibition effect of GAS on mHtt in our next study. In summary, GAS can promote the degradation of mHtt by activating the UPS and ALP, making it a potential therapeutic agent for HD.

Abstract Aim To explore the relationship between university nursing students' academic procrastination, mindfulness, and future time perspective. Design A cross‐sectional study. Methods A total of 343 university nursing students recruited from eight provinces in China have reported procrastination characteristics through fulfilling an online website link. The main instruments involved Mindfulness Attention Awareness Scale (MAAS), Zimbardo Time Perspective Scale, and Procrastination Assessment Scale (PASS). Results Participants who self‐assessed higher frequency and degree of academic procrastination tended to possess lower future time consciousness, and lower mindfulness. Mindfulness served as a mediation effect between future time perspective and academic procrastination. The study indicates that weakening an individual's procrastination can be alleviated through future time awareness and mindfulness. Concentrating on influencing factors, strengthening nursing student's future time perspective, and practicing mindfulness training could assist educators to decrease students' procrastination intentions and behaviours.

With the rapid advancement of urbanization, the development and utilization of urban underground space resource (UUSR) has become one of the dominant features. However, in certain areas, the development of UUSR may cause disasters and accidents, such as ground collapse, settlements, and tunnel water gushing. Geological environmental factors (GEFs) are recognized as the fundamental constraining factor of UUSR development. In this paper, quality based on GEFs is defined to assess the development difficulty degree of UUSR. A 3D assessment framework is proposed based on 3D geological modelling and the interval continuous mathematical model (ICMM). The subjective and objective joint weight method of analytic hierarchy process and entropy weight method (AHP–EWM) is utilized to determine the weight of each indicator. The quality index (QI) of each spatial node of the 3D geological model is calculated by the ICMM mathematical model. A case study conducted in the Jiangbei New District of Nanjing, China, serves as a demonstration of the UUSR assessment. The results clearly illustrate the 3D distribution characteristics of the quality in the study area, offering valuable insights for future 3D urban underground space planning.

With the warming and humidification process in the Northwest Arid Zone over the past 30 years, the runoff of a vast majority of rivers has been affected to different degrees. In this paper, the runoff from the Weigan River, a typical inland river in the arid zone of Northwest China, is taken as an example, and seven types of CMIP6 data are selected with the help of a SWAT model to predict the runoff volume of the Weigan River in the next 30 years under climate change. The results show that (1) the SWAT model can simulate the runoff from the Weigan River well and has good applicability in this study area. (2) With an increase in radiative forcing, the temperature, precipitation and runoff in the study area show an increasing trend. (3) Under the four radiative forcing scenarios in 2030 and 2050, the runoff from the Weigan River out of the mountain is predicted to be maintained at 25.68 to 30.89 × 108 m3, which is an increase of 1.35% to 21.91% compared with the current runoff, of which the contribution to the increase in future runoff caused by the changes in temperature and precipitation is 68.71% and 27.24%, respectively. It is important to explore the impact of climate change on the runoff from the Weigan River to understand the impact of climate change on the Northwest Arid Region scientifically and rationally, and to provide a scientific basis for evaluating the risk of climate change and formulating policies to deal with it.

Abstract Objective To compare the influence of minimally invasive esophagectomy (MIE) and open esophagectomy (OE) on postoperative pulmonary function in patients with esophageal cancer. Methods Studies about the influence of MIE and OE on postoperative pulmonary function in esophageal cancer patients were searched from PubMed, EMBASE, the Cochrane Library, CNKI, Chinese Science and Technology Journal Database, CBM, and Wanfang Data from inception to March 18, 2021. Meta-analysis was performed using the RevMan 5.3. Results This analysis included eight studies, enrolling 264 patients who underwent MIE and 257 patients who underwent OE. The meta-analysis results showed that the MIE group had a higher outcome regarding the percent predicted vital capacity (%VC), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and maximum voluntary ventilation (MVV) 1 month after surgery than the OE group. In addition, those who underwent MIE had lower ΔVC%, ΔFVC, and ΔFEV1 between pre-operation and 1 month after surgery than those who underwent OE. There is no statistical difference between the two groups in ΔMVV. Conclusion Compared with OE, MIE has a more protective effect on postoperative pulmonary function. However, due to the small number of included literature and all cohort studies, this finding needs to be validated with larger samples and higher quality RCT studies.

Aiming to precisely identify a compound fault of rolling bearing, the paper has contributed a fault characteristic enhancement method by combing entropy weight method (EWM) and intrinsic time scale decomposition (ITD). Firstly, to effectively segregate frequency components in vibration signals, proper rotation components (PRCs) were obtained by decomposing vibration signals based on ITD. Secondly, in view of the fact that amplitude, variance and correlation coefficient vary greatly in a bearing fault accompanied by impact components, parameter evaluation indexes were brought in to depict the fault characteristics of PRCs, including average, variance, correlation coefficient, margin factor, kurtosis, impulse factor, peak factor and so on. Thirdly, weight coefficient of each parameter index was calculated by entropy weight method and the characteristics of each PRC highlighted based on that. Finally, the signals were reconstructed according to the PRCs whose characteristics had been enhanced. Meanwhile reconstructed signals were denoised with singular differential spectrum (SDS) to reduce the influence of noise components, and then the type of compound fault was distinguished grounded on the frequency spectrum. To further prove the efficiency of proposed method, it is compared with other methods (SDS, ITD + entropy method). The result indicates that the proposed method can further highlight the characteristic information of compound faults of bearing and embody more exact identification and judgment on the type of faults.

Abstract Background Although postoperative pulmonary infection (POI) commonly occurs in patients with esophageal cancer after curative surgery, a patient-specific predictive model is still lacking. The main aim of this study is to construct and validate a nomogram for estimating the risk of POI by investigating how perioperative features contribute to POI. Methods This cohort study enrolled 637 patients with esophageal cancer. Perioperative information on participants was collected to develop and validate a nomogram for predicting postoperative pulmonary infection in esophageal cancer. Predictive accuracy, discriminatory capability, and clinical usefulness were evaluated by calibration curves, concordance index (C-index), and decision curve analysis (DCA). Results Multivariable logistic regression analysis indicated that length of stay, albumin, intraoperative bleeding, and perioperative blood transfusion were independent predictors of POI. The nomogram for assessing individual risk of POI indicated good predictive accuracy in the primary cohort (C-index, 0.802) and validation cohort (C-index, 0.763). Good consistency between predicted risk and observed actual risk was presented as the calibration curve. The nomogram for estimating POI of esophageal cancer had superior net benefit with a wide range of threshold probabilities (4–81%). Conclusions The present study provided a nomogram developed with perioperative features to assess the individual probability of infection may conducive to strengthen awareness of infection control and provide appropriate resources to manage patients at high risk following esophagectomy.

In order to use water resources more efficiently, the construction of water conservation projects in dryland watersheds has changed the natural water cycle processes. This study used the SWAT (Soil and Water Assessment Tool) model coupled with the glacier module to simulate the hydrological processes in the upper reaches of the Weigan River estuary from 1965 to 1991, to restore and quantitatively evaluate the conditions of the estuarine runoff in the no-reservoir scenario, and to analyse the impact of the construction of water conservation projects on the estuarine runoff based on this model. The results show that the SWAT model has good applicability in the study area, with 41.45% and 58.55% of the increase in runoff due to increased precipitation and temperature, respectively, over the 52 years study period. The degree of influence of the construction of water conservation projects on runoff from the mountain in different seasons was spring > autumn > winter > summer, with 83.28% of the spring runoff being influenced by artificial regulation. The construction of water conservation projects has alleviated water shortage problems to a certain extent, and is an effective measure for achieving the efficient allocation of water resources in arid areas.

AbstractRed-bed argillaceous siltstone is one of main types of rocks composing unstable slopes on both banks of water diversion project from the Yangtze to Huaihe River and is prone to deterioration after subjected to drying-wetting cycle conditions during water diversion project operation. The study of the damage degradation and the constitutive relationship of rocks subjected to drying-wetting cycle process is therefore of critical scientific importance. In this paper, laboratory tests were conducted to investigate the effect of drying-wetting cycles on the mechanical properties and microstructural characteristics. The experimental results show that the microstructure of the sample surface is no longer dense and uniform and the porosity of tested samples significantly increases with drying-wetting cycles increasing. After subjected to cycles of drying-wetting, the compaction stage of the stress-strain curve becomes longer with more pronounced nonlinear features, while uniaxial compression strength (UCS) and elastic modulus drop obviously. Combined with the evolution characteristics of microstructure found as the porosity grew, UCS and elastic modulus gradually decline. Additionally, from the perspective of energy analysis, the input energy density and dissipated energy density gradually extended with the increasing strain, and the elastic energy density increased first and then declined. As the number of drying-wetting cycles increases, the energy density of samples all present linear fell. Based on the evolution of dissipated energy, a new damage model of red-bed argillaceous siltstone subjected to drying-wetting cycles was established by introducing compaction coefficient. The coefficients of determination (R2) of the constitutive model are always greater than 0.85, indicating that the proposed model is generally in good agreement with the experimental data under different drying-wetting cycles. This paper has specific research and reference value to understand the damage evolution characteristics of red-bed argillaceous siltstone under cyclic drying-wetting.

Background: The aim of this study was to investigate the effects of transcatheter arterial chemoembolization (TACE) combined with sorafenib on tumor angiogenesis. Materials and methods: Thirty New Zealand rabbit VX2 liver cancer model animals were divided into five groups, which received either normal saline (A), TACE (B), sorafenib (C), sorafenib followed by TACE (D), or TACE followed by sorafenib (E). Serum vascular endothelial growth factor (VEGF) levels were measured before and after TACE via ELISA. Immunohistochemistry for CD34 was performed to evaluate microvessel density (MVD), and ultrasonography was used to access tumor volume. Results: VEGF levels declined in group C but increased significantly on the 3rd post-operative day in groups B, D, and E. Levels decreased after the 7th post-operative day. Peak levels were significantly lower in group D than in groups B and E. On the 14th post-operative day, VEGF levels were the lowest in group C, followed by those in groups D and B. MVD was the lowest in group C followed by that in group D and E, and was the highest in group B. Group D had the smallest tumor volume. HE staining of tumor tissues from group C showed apoptosis in a scattered patchy pattern, whereas in groups B, D, and E, large areas of tumor cell necrosis were visible. Conclusion: TACE can up-regulate serum VEGF levels, which in turn accelerates the formation of new blood vessels. Thus, TACE combined with sorafenib inhibits VEGF and angiogenesis, and pre-operative administration of sorafenib has a more superior anti-angiogenic effect than post-operative administration. Keywords: Transcatheter arterial chemoembolization (TACE), Sorafenib, Hepatocellular carcinoma, Vascular endothelial growth factor (VEGF), Microvessel density (MVD)

With so many advantages such as environmental friendliness, fast-growing, high strength-to-weight ratio, sustainability, and the capability of being reused or recycled, bamboo structures has gained more and more attention for scientists. This paper shows the feasibility of the design of an office building using laminated bamboo lumbers in compliance with the Chinese standards as GB50009-2012, GB50011-2010, GB50016-2014, and GB 50005-2017. Detailed information about the materials and building were offered. A lot of related construction photos were offered to show the building process. This case is a very good application example for laminated bamboo lumber buildings and has attracted many engineers’ attention in industrial field. Laminated bamboo lumber structures should have a bright future. It should become one main structure form in civil engineering area. However, due to none existing engineered bamboo structures design standard now, engineers have to take reference to standards for timber structures. Setting up the standard system is very important for engineered bamboo structures’ application. Through more and more scientists’ hard working, it might be not a long way to build the code system.

The Maodong Fault (China) was mainly active during the Late Pleistocene. However, in the past century, numerous destructive earthquakes have occurred along the fault zone, indicating its continuing activity. Therefore, refined monitoring of the tectonic activity along the fault is required. Boiling-Wells located in the Maodong Fault Zone were selected for this purpose. The parameters, including the rare earth elements (REE) and gas components, such as CO2, Rn, and Total Volatile Organic Compounds (TVOC), in the wells were analyzed. By combining field observations with the analytical data, we constrained the relationships between the anomalies of the hydrochemical composition and the gas composition in the Boiling-Wells and the Maodong Fault: (1) CO2 and TVOC in the Boiling-Wells originated from Cenozoic magmatism and associated intrusive rocks. High concentrations of Rn are closely linked to tectonic activities of the Maodong Fault. CO2, TVOC, and Rn are all transported to the Boiling-Wells along the Maodong Fault, with CO2 acting as a carrier gas for Rn. (2) REE in the Boiling-Wells was mainly sourced from CO2 fluids that originated from deep-seated Cenozoic magmas and intrusive rocks. The concentrations of the REE and their distribution patterns were controlled by the input of CO2 fluids and by epigenetic processes. (3) The abnormally high contents of Ca2+, HCO3−, Pb2+, and Al3+ in the Boiling-Wells are attributed to the migration of externally-derived (deep) CO2 fluids through the Maodong Fault. (4) The anomalies of the gaseous (Rn, CO2, and TVOC) and hydrochemical components (Ca2+, HCO3−, Pb2+, Al3+, ∑REE, and REE patterns) in the Boiling-Wells are closely related to the tectonic activity of the Maodong Fault. Therefore, the long-lasting Boiling-Wells provide an excellent geochemical window into the evolution of the Maodong Fault. Our study documents that the contents and variations of specific hydrochemical and gaseous components of Boiling-Wells are well-suited geochemical tracers to identify and characterize the tectonic activity of the Maodong Fault. This method is also applicable for the monitoring of tectonic activities of major faults zones with comparable preconditions worldwide.

IL12 is an immune-stimulatory cytokine for key immune cells including T cells and NK cells. However, systemic administration of IL12 has serious side effects that limit its clinical application in patients. Recently, synthetic Notch (synNotch) receptors have been developed that induce transcriptional activation and deliver therapeutic payloads in response to the reorganization of specific antigens. NK92 cell is a human natural killer (NK) cell line which has been developed as tools for adjuvant immunotherapy of cancer. Here, we explored the possibility of using synNotch receptor-engineered NK92 cells to selectively secrete IL12 at the tumor site and increase the antitumor activities of chimeric antigen receptor (CAR)-modified T cells. Compared with the nuclear factor of activated T-cells (NFATs) responsive promoter, which is another regulatory element, the synNotch receptor was better at controlling the expression of cytokines. NK92 cells transduced with the GPC3-specific synNotch receptor could produce the proinflammatory cytokine IL12 (GPC3-Syn-IL12-NK92) in response to GPC3 antigen expressed in cancer cells. In vivo GPC3-Syn-IL12-NK92 cells controlling IL12 production could enhance the antitumor ability of GPC3-redirected CAR T cells and increase the infiltration of T cells without inducing toxicity. Taken together, our results demonstrated that IL12 supplementation by synNotch-engineered NK92 cells could secrete IL12 in a target-dependent manner, and promote the antitumor efficiency of CAR-T cells. Local expression of IL12 by synNotch-engineered NK92 cells might be a safe approach to enhance the clinical outcome of CAR-T cell therapy.

Abstract Background Psychological flexibility (PF) is defined as the ability to pursue valuable life goals despite the existence of distress. The Personalized Psychological Flexibility Index (PPFI) is a new measure of psychological flexibility that can address existing deficiencies. This study aimed to translate and validate the psychometric characteristics of the Chinese version of the PPFI among medical college students. Methods The study was conducted in two phases. Phase 1 involved the translation and cross-cultural adaptation of the PPFI according to guidelines recommended by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Phase 2 was a cross-sectional survey conducted on 945 medical college students in China. The psychometric performances of the scale were assessed using construct validity, divergent validity, criterion validity, incremental validity, internal consistency, and test-rest reliability. Results The exploratory factor analysis (EFA, n1 = 440) showed that the Chinese version of the PPFI consisted of 3 factors, with a total of 15 items. The confirmatory factor analysis (CFA, n2 = 440) showed that the three-factor structure fit well (χ2/ $$df$$ df =2.469, SRMR = 0.051, RMSEA = 0.058, GFI = 0.94, CFI = 0.985). The total Chinese PPFI score had a moderate positive association with the Comprehensive Assessment of Acceptance and Commitment Therapy (CompACT, r = 0.344) and a negative association with the Acceptance and Action Questionnaire-II (AAQ-II, r = -0.334). Furthermore, the Chinese PPFI demonstrated good internal consistency (Cronbach's α = 0.826) and test–retest reliability (ICC = 0.817, p

Abstract Identifying the location of a potential noise source assists in understanding the characteristics of the seismic or volcanic activity and provides valuable information for hazard assessment. Unlike the conventional waveform-based techniques that rebuild the source energy into the possible source region, we apply a simplified method to determine the absolute location of the noise source based on the station-pair time-delays from ambient noise interferometry. Synthetic tests demonstrate the robustness of the method and the locating precision is mainly influenced by the signal-to-noise ratio of the synthetic waveforms, and the higher frequency bandwidth source signals are more likely to result in accurate detection of the source. An application at the Central Tien Shan indicates that our method is capable of locating the known virtual source from the empirical Green’s functions. Furthermore, assuming a surface wave velocity, the depth of the source can be generally recovered from ambient noise interferometry in a simplified 3-D homogeneous model. The new method sheds light on applications of ambient noise interferometry for locating potential sources, making it suitable for detecting time-dependent behavior.

Abstract The destructive 2015 Mw7.8 Gorkha earthquake occurred in the Main Himalayan Thrust due to the collision of the Indian and Asian plates, which provides a unique opportunity to understand the deep dynamic processes and seismogenic mechanisms of strong earthquakes. We construct a regional-scale shear-wave velocity model of the crust and uppermost mantle using ambient seismic noise and teleseismic surface wave at periods of 5–100 s around the Gorkha earthquake region. The new shear-wave velocity model exhibits prominently lateral heterogeneities in the Gorkha earthquake areas. We observe a high-velocity (high-V) zone around the Gorkha main shock in the Main Himalayan Thrust, indicating the existence of a high-strength asperity that sustains the stress accumulating. The aftershocks are primarily located in the low-velocity (low-V) anomalies and enclosed by two high-V anomalies, which appear to act as structural barriers that influence the spread of the aftershocks. Prominent low-Vanomalies from the lower crust to the mantle lithosphere are observed along the north–south trending rifts, suggesting the hot materials upwelling due to the tearing of the northward subducting Indian lithosphere. These observations may indicate that seismic velocity heterogeneity could play an essential role in earthquake initiation and the rupture process.

Abstract Electrochemical research often requires stringent combinations of experimental parameters that are demanding to manually locate. Recent advances in automated instrumentation and machine-learning algorithms unlock the possibility for accelerated studies of electrochemical fundamentals via high-throughput, online decision-making. Here we report an autonomous electrochemical platform that implements an adaptive, closed-loop workflow for mechanistic investigation of molecular electrochemistry. As a proof-of-concept, this platform autonomously identifies and investigates an EC mechanism, an interfacial electron transfer (E step) followed by a solution reaction (C step), for cobalt tetraphenylporphyrin exposed to a library of organohalide electrophiles. The generally applicable workflow accurately discerns the EC mechanism’s presence amid negative controls and outliers, adaptively designs desired experimental conditions, and quantitatively extracts kinetic information of the C step spanning over 7 orders of magnitude, from which mechanistic insights into oxidative addition pathways are gained. This work opens opportunities for autonomous mechanistic discoveries in self-driving electrochemistry laboratories without manual intervention.