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Incretins are gut-produced peptide-hormones that potentiate insulin secretion, especially after food intake. The concept of incretin was formed more than 100 years ago, even before insulin was isolated and utilized in the treatment of subjects with type 1 diabetes. The first incretin, glucose-dependent insulinotropic polypeptide (GIP), was identified during later 1960’s and early 1970’s; while the second one, known as glucagon-like peptide-1 (GLP-1), was recognized during 1980’s. Today, GLP-1-based therapeutic agents [also known as GLP-1 receptor (GLP-1R) agonists, GLP-1RAs] are among the first line drugs for type 2 diabetes. In addition to serving as incretin, extra-pancreatic functions of GLP-1RAs have been broadly recognized, including those in the liver, despite the absence of GLP-1R in hepatic tissue. The existence of insulin-independent or gut-pancreas-liver axis-independent hepatic function of GLP-1RAs explains why those therapeutic agents are effective in subjects with insulin resistance and their profound effect on lipid homeostasis. Following a brief review on the discovery of GLP-1, we reviewed literature on the exploration of hepatic function of GLP-1 and GLP-1RAs and discussed recent studies on the role of hepatic hormone fibroblast growth factor 21 (FGF21) in mediating function of GLP-1RAs in animal models. This was followed by presenting our perspective views.

Abstract There is limited research on the relationship between Life's Essential 8 (LE8) score and metabolic dysfunction-associated steatotic liver disease (MASLD). Our aim is to investigate the relationship between overall lifestyle assessed by LE-8 score and MASLD in a nationally representative sample. We employed the LE8 score to comprehensively evaluate cardiovascular health, the assessment of MASLD primarily utilized the Fatty Liver Index. The weighted logistic regression models, restrictive cubic splines (RCS), subgroup analyses and the weighted quantile sum (WQS) regression were used to evaluate the relationship between the cardiovascular health and MASLD. Logistic regression models revealed that higher LE8 scores were associated with lower odds of having MASLD. The RCS revealed a significant nonlinear dose–response relationship between LE8 scores and MASLD. The WQS regression model indicated that blood glucose contributed the most to the risk of MASLD. The subgroup analysis indicates that there are significant differences in this association across age, educational level, and poverty income ratio. Our study suggests that an inverse correlation between LE8 and the risk of MASLD. Our findings underscore the utility of the LE8 algorithm in MASLD risk assessment and provide support for MASLD prevention through the promotion of healthy lifestyles.

Traumatic spinal cord injury (SCI) always leads to severe neurological deficits and permanent damage. Neuroinflammation is a vital process of SCI and have become a promising target for SCI treatment. However, the neuroinflammation-targeted therapy would hinder the functional recovery of spinal cord and lead to the treatment failure. Herein, a biomimic anti-neuroinflammatory nanoplatform (DHCNPs) was developed for active neutrophil extracellular traps (NETs) targeting and SCI treatment. The curcumin-loaded liposome with the anti-inflammatory property acted as the core of the DHCNPs. Platelet membrane and neutrophil membrane were fused to form the biomimic hybrid membrane of the DHCNPs for hijacking neutrophils and neutralizing the elevated neutrophil-related proinflammatory cytokines, respectively. DNAse I modification on the hybrid membrane could achieve NETs degradation, blood spinal cord barrier, and neuron repair. Further studies proved that the DHCNPs could reprogram the multifaceted neuroinflammation and reverse the SCI process via nuclear factor kappa-B (NF-κB) pathway. We believe that the current study provides a new perspective for neuroinflammation inhibition and may shed new light on the treatment of SCI.

With the large-scale commercial use of the global 5G network and the rapid growth of mobile Internet traffic, more abundant wireless spectrum resources can be released, and the demand for high-speed optical modules in wireless front-haul networks is increasingly prominent. Focusing on the key technologies of 50 Gbit/s front-haul optical modules, two main networking methods were deeply analyzed, the typical transmission distance and link loss were analyzed, the maximum and minimum dispersion values of coarse wave division multiplexing (CWDM) wavelengths in a 10 km scenario were explored, and the corresponding dispersion compensation strategies were studied. Through experiments, the changes in optical power penalty of different multi-path interference (MPI) were verified, and the potential impact of MPI noise on error performance was analyzed in detail. In addition, deep research on the optoelectronic chip scheme of 50 Gbit/s modules was conducted, the parameters of various types of optical modules were rigorously tested, standardized suggestions for the optoelectronic interface parameters of 50 Gbit/s front-haul modules were proposed, the current standard status of 50 Gbit/s modules at home and abroad was detailed, and the development trend of future applications was prospected.

The deposition of spray droplets is a hot topic in the field of plant protection. The air-induction nozzle, which is commonly used in agricultural spray, can produce droplets containing bubbles. However, few studies have addressed the deposition of hollow droplets. In the present study, we used experimental and numerical methods to investigate the deposition of hollow droplets. Three kinds of liquid—water, oil-based emulsion and organosilicon—were used to produce hollow droplets, and the diameter of droplets varied from 3 to 4.5 mm. Both hydrophilic and hydrophobic surfaces were selected as deposition targets. The results show that the deposition of hollow droplets can generate a central jet, which is similar to the Wortington jet. High deposition velocity and the large bubble volume were responsible for the large attainable height of the central jet. On the hydrophilic surface, for water hollow droplets with Weber number (We) ranging from 350 to 391, the central jet began to break up as the bubble fraction of the hollow droplet reached 0.15. Based on the numerical results, it was found that the internal pressure difference between the bottom liquid and the air cavity leads to the formation of the central jet. The bubble volume and impact velocity were both positively correlated with the internal pressure difference. The oil-based emulsion promoted the adherence of the hollow droplet by lubricating the hydrophobic surface. The oil-based emulsion hollow droplets shifted from rebounding to adhering on the hydrophobic surface as the emulsion concentration reached 0.4%.

Abstract Background Cholelithiasis is a common digestive system disease that imposes major burden on patients and society. Investigating the relationship between dietary factors and cholelithiasis risk can provide a basis for disease prevention. Previous studies on milk intake and cholelithiasis incidence have been limited.Therefore, the aim of our study was to assess the association between milk consumption and the incidence of cholelithiasis in males and females. Methods We selected 14,722 adults (≥ 18 years old) from National Center for Health Statistics (NHANSE) 2017–2020, and collected general characteristics of patients in the database, such as age, gender, race and body mass index (BMI), as well as dietary information (milk consumption). The occurrence of cholelithiasis was used as the outcome event, and the group was divided into cholelithiasis and non-cholelithiasis groups according to the outcome event. We used logistic regression models in generalized linear model (GLM) functions, controlling for demographic, lifestyle, and dietary factors, to estimate the association between milk intake and the incidence of cholelithiasis in males and females. Results A total of 14,722 adults were included. In the present study, the overall weighted prevalence of cholelithiasis was 10.96%, with 15.18% and 6.48% prevalence in females and males, respectively. Compared to infrequent milk intake, frequent milk intake (once a week or more) in females was associated with reduced cholelithiasis risk (OR 0.74, 95% CI 0.61–0.90). Daily milk intake in males was also related to lower cholelithiasis risk (OR 0.69–0.82). As adjusted variables increased in the models, predictive performance was improved (AUC 0.711 in females, 0.730 in males). Conclusions Appropriate milk intake may correlate with decreased cholelithiasis risk. Our study provides a basis for dietary interventions against gallstones, but prospective studies are needed to verify the results.

Background With the acceleration of population aging, multiple chronic diseases have become common in the elderly, and the research on multiple chronic diseases in the elderly is also increasing. However, few studies have been conducted to analyze its progress and hotspots. Objective To analyze the hotspots of multiple chronic diseases in the elderly at home and abroad, revealing the hotspots in frontiers research, so as to provide a reference for related researchers to track cutting-edge information. Methods The literatures related to multiple chronic diseases in the elderly were retrieved from Web of Science, Scopus, CNKI, Wanfang Data, VIP, PubMed, Chinese Medical Association Journal Full-text database, and APA-PsycINFO database of the American Psychological Association with the retrieval time of 2010-2021, based on text mining technology and bibliometrics method, etc. CiteSpace 6.1.3, PASW 18, BICOMB 2.04 and other software were used to analyze and visualize the trends in number of papers published, sources, authors, institutions, keywords and other aspects of literature publication. Strategic coordinate maps were drawn to analyze research hotspots in the field. Results Finally, 9 392 literatures related to multiple chronic diseases in the elderly were involved, including 5 776 literatures in foreign language and 3 616 literatures in Chinese. The numbers of literatures related to multiple chronic diseases in the elderly both in foreign language and Chinese have increased exponentially in the past decade, with the annual growth rate of 13.27% in Chinese literature and 15.84% in foreign literature, suggesting the development stage of multiple chronic diseases in the elderly. Five mainstream research hotspots have been identified in both Chinese and foreign literatures. There are more literatures related to multiple chronic disease such as chronic obstructive pulmonary disease, diabetes mellitus, hypertension, and respiratory diseases. The foreign literatures have focused more on the psychiatric comorbidity, followed by somatic comorbidities such as diabetes mellitus, hypertension, and heart failure. Conclusion The analysis results shows that the field of multiple chronic diseases in the elderly is in a rapid development stage. Analysis of foreign literature shows that psychiatric comorbidity is a relatively hot topic but not mature enough, research results related to multiple chronic diseases in the elderly are abundant and diversified, but the research depth is in sufficient. Domestic literature analysis shows that chronic obstructive pulmonary disease combined with respiratory diseases in the elderly is at the core of the field, and there is a lack of studies related to psychiatric comorbidity such as depression and mutiple chronic diseases such as health situation, nursing and health care, which may become the main direction of research development in the future.

Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor protein predominantly expressed in microglia within the central nervous system (CNS). TREM2 regulates multiple microglial functions, including lipid metabolism, immune reaction, inflammation, and microglial phagocytosis. Recent studies have found that TREM2 is highly expressed in activated microglia after ischemic stroke. However, the role of TREM2 in the pathologic response after stroke remains unclear. Herein, TREM2-deficient microglia exhibit an impaired phagocytosis rate and cholesteryl ester (CE) accumulation, leading to lipid droplet formation and upregulation of Perilipin-2 (PLIN2) expression after hypoxia. Knockdown of TREM2 results in increased lipid synthesis (PLIN2, SOAT1) and decreased cholesterol clearance and lipid hydrolysis (LIPA, ApoE, ABCA1, NECH1, and NPC2), further impacting microglial phenotypes. In these lipid droplet-rich microglia, the TGF-β1/Smad2/3 signaling pathway is downregulated, driving microglia towards a pro-inflammatory phenotype. Meanwhile, in a neuron-microglia co-culture system under hypoxic conditions, we found that microglia lost their protective effect against neuronal injury and apoptosis when TREM2 was knocked down. Under in vivo conditions, TREM2 knockdown mice express lower TGF-β1 expression levels and a lower number of anti-inflammatory M2 phenotype microglia, resulting in increased cerebral infarct size, exacerbated neuronal apoptosis, and aggravated neuronal impairment. Our work suggests that TREM2 attenuates stroke-induced neuroinflammation by modulating the TGF-β1/Smad2/3 signaling pathway. TREM2 may play a direct role in the regulation of inflammation and also exert an influence on the post-ischemic inflammation and the stroke pathology progression via regulation of lipid metabolism processes. Thus, underscoring the therapeutic potential of TREM2 agonists in ischemic stroke and making TREM2 an attractive new clinical target for the treatment of ischemic stroke and other inflammation-related diseases.

Abstract Introduction The Davos Assessment of Cognitive Biases Scale (DACOBS) is widely used to assess cognitive biases in patients who have schizophrenia. However, the lack of a modified Chinese‐language version of the DACOBS (MCL‐DACOBS) precludes Chinese schizophrenic patients from treatment aimed at normalizing cognitive biases, impacting their prognosis. Here, we aimed to produce a DACOBS for China and test the validity and reliability of the resultant MCL‐DACOBS. Methods Eighteen researchers collaborated to develop the MCL‐DACOBS: A total of 15 researchers modified and translated the English version of the DACOBS, 1 native‐English‐speaking researcher back‐translated the scale, and 2 Chinese sinologists localized and optimized the language of the MCL‐DACOBS. Forty‐two volunteers checked the scale items’ comprehensibility, and the two sinologists performed further localization and optimization based on their feedback. The final version of the MCL‐DACOBS used in this study was thus derived from the harmonized English‐language version of the scale. Confirmatory factor analyses (CFAs) were used to examine the best latent structure of the MCL‐DACOBS. Cronbach's α and intraclass correlation coefficients (ICCs) were used to check the reliability. The discriminative ability of the MCL‐DACOBS was assessed according to the area under the receiver operating characteristic curve. Results The CFA showed that all items loaded onto factors with loadings >0.400. A two‐factor structure showed a good model fit (root mean square error of approximation = .018, Tucker–Lewis index = .978, comparative fit index = .984). Promax rotation demonstrated that each item had a high factor load (0.432–0.774). Cronbach's α coefficient and ICC for the MCL‐DOCABS were .965 and .957, respectively, indicating that the scale has ideal reliability. Conclusion The MCL‐DACOBS has good validity and good reliability, and its psychometric properties indicate that it is a valid tool for measuring cognitive biases in Chinese patients with schizophrenia.

The design methods for gradient coils are mostly based on discrete extrinsic methods (e.g., the Biot–Savart integration calculation), for which the surface normal vector strongly influences any numerical calculation of the discretized surface. Previous studies are mostly based on regular or analytical surfaces, which allow normal vectors to be expressed analytically. For certain applications, design methods for extending current-carrying surfaces from developable or analytic geometries to arbitrary surfaces generated from a scanned point cloud are required. The key task is to correctly express the discretized normal vectors to ensure geometrical accuracy of the designed coils. Mathematically, it has been proven that applying a Delaunay triangulation to approximate a smooth surface can result in the discrete elemental normal vectors converging to those of the original surface. Accordingly, this article uses Delaunay triangulation to expand upon previous design methods so that they encompass arbitrary piecewise continuous surfaces. Two design methods, the stream function and the so-called solid isotropic material with penalization (SIMP) method, are used to design circumvolute and noncircumvolute gradient coils on general surfaces.

Background: Pancreatic fistula (PF) and biliary fistula (BF) are two major leakage complications after pancreatoduodenectomy (PD). The aim of this study is to investigate the risk factors of PF and BF after laparoscopic PD (LPD). Materials and Methods: We conducted a retrospective analysis of 500 patients who underwent LPD from 1 April 2015 to 31 March 2020. Clinical data from patients were analysed using multivariate logistic regression analysis. Results: PF occurred in 86 (17.2%) patients. Univariate and multivariate analysis indicated that the soft texture of the pancreas (P = 0.001) was the independent risk factor for PF. BF occurred in 32 (6.4%) patients. Univariate and multivariate analysis indicated that history of cardiovascular disease (P < 0.001), surgical time (P = 0.005), pre-operative CA125 (P = 0.036) and pre-operative total bilirubin (P = 0.044) were independent risk factors for BF. Conclusion: The texture of the pancreas was an independent risk factor for PF after LPD, which was consistent with the literatures. In addition, history of cardiovascular disease, surgical time, pre-operative CA125 and pre-operative total bilirubin were new independent risk factors for BF after LPD. Therefore, patients with high-risk factors of BF should be informed that they are at a high risk for this complication.

Voltage source converter based high-voltage direct current (VSC-HVDC) transmission technology has been extensively employed in power systems with a high penetration of renewable energy resources. However, connecting a voltage source converter (VSC) to an AC weak grid may cause the converter system to become unstable. In this paper, a phase-shift phase-locked loop (PS-PLL) is proposed wherein a back electromotive force (BEMF) observer is added to the conventional phase-locked loop (PLL). The BEMF observer is used to observe the voltage of the infinite grid in the stationary $\alpha\beta$ frame, which avoids the problem of inaccurate observations of the grid voltage in the $dq$ frame that are caused by the output phase angle errors of the PLL. The VSC using the PS-PLL can operate as if it is facing a strong grid, thus enhancing the stability of the VSC-HVDC system. The proposed PS-PLL only needs to be properly modified on the basis of a traditional PLL, which makes it easy to implement. In addition, because it is difficult to obtain the exact impedance of the grid, the influence of short-circuit ratio (SCR) estimation errors on the performance of the PS-PLL is also studied. The effectiveness of the proposed PS-PLL is verified by the small-signal stability analysis and time-domain simulation.

Our previous study demonstrated the potential therapeutic role of human neural stem cell-derived exosomes (hNSC-Exo) in ischemic stroke. Here, we loaded brain-derived neurotrophic factor (BDNF) into exosomes derived from NSCs to construct engineered exosomes (BDNF-hNSC-Exo) and compared their effects with those of hNSC-Exo on ischemic stroke both in vitro and in vivo. In a model of H2O2-induced oxidative stress in NSCs, BDNF-hNSC-Exo markedly enhanced cell survival. In a rat middle cerebral artery occlusion model, BDNF-hNSC-Exo not only inhibited the activation of microglia, but also promoted the differentiation of endogenous NSCs into neurons. These results suggest that BDNF can improve the function of NSC-derived exosomes in the treatment of ischemic stroke. Our research may support the clinical use of other neurotrophic factors for central nervous system diseases.

Abstract Based on the modular topology and the traditional voltage‐sourced converter (VSC) model, this paper presents an isolated modular multi‐level AC/AC converter with high‐frequency (HF) link and pulse flip circuit for fractional frequency transmission system (FFTS) application. The proposed converter uses the HF transformer to realize electrical isolation, omitting the industrial frequency (IF) transformer with large volume and heavy weight. In the primary side of the HF transformer, the power transmission is realized by the rectifier and the inverter. In the secondary side of the HF transformer, the double H‐bridges are used to realize the natural freewheeling of the leakage current, which solves the problem of voltage overshoot. On the basis of carrier phase‐shifted pulse width modulation (CPS‐PWM), an improved modulation strategy is proposed to realize the HF output voltage of the inverter. It has the advantages of easy expansion, no circulation current, good output voltage quality, low cost and no need of offshore converter station, so it has great potential in the field of offshore wind power grid connection. The working principle, natural freewheeling modes, modulation method and overall system control scheme of the proposed topology are introduced in detail, and the feasibility of the proposed topology is verified by simulation in MATLAB/Simulink environment and test through APPSIM platform.

Abstract Based on a practical long‐distance large‐capacity transmission engineering case, the small‐signal stability of fractional frequency transmission system (FFTS) with Y‐connected modular multi‐level converter (Y‐MMC) is mainly researched in this paper. Different from the previous control strategies of Y‐MMC, this paper establishes a frequency decoupling mathematical model and proposes the decoupling control strategies. Then, the small‐signal model of the Y‐MMC system is obtained. Considering the existence of phase locked loop (PLL) will deteriorate the stability of the system under weak grid, this paper applies the short‐circuit ratio (SCR) for analysis and proposed a new structure of PLL, called phase‐shifted PLL (PS‐PLL), to improve the small‐signal stability of the system. In addition, for better stability and dynamic response performance of the closed‐loop control system, this paper proposes a new parameter optimization objective function for parameters adjustment. Controller parameters optimization is conducted by using the particle swarm optimization (PSO) algorithm and stability evaluation of the system is conducted based on the eigenvalue distribution. Finally, the feasibility and superiority of the proposed strategies and optimization are verified in MATLAB/ Simulink.

Background: Traumatic brain injury (TBI) is associated with a range of neural changes. A comprehensive understanding of the injury-induced lysine acetyltransferase 6A (KAT6A) response, particularly the temporal profile of biochemical alterations, is crucial to design effective therapeutic interventions. Methods: Experiments were performed in male Sprague-Dawley rats. The influence of post-traumatic hypothermia (32°C) or hyperthermia (39°C) on the temporal and regional expression profiles of KAT6A was assessed after moderate or severe TBI. qPCR and western blotting were used to determine the expression of KAT6A in different groups. Results: In the ipsilateral and contralateral hemispheres, significantly lower protein and mRNA expression of KAT6A was found after TBI than sham injury. Moreover, two expression minima of KAT6A were observed in the cortex and hippocampus of the ipsilateral hemisphere. A decrease in injury severity was associated with lower levels of KAT6A mRNA at 12 h and protein at 24 h, but KAT6A mRNA at 48 h and protein at 72 h had alterations. Compared with normothermia and hyperthermia, post-traumatic hypothermia intensified the decrease in KAT6A at both the mRNA and protein levels. In contrast, hyperthermia, as compared with normothermia, did not significantly affect the levels of KAT6A mRNA at 12 h and protein at 24 h, but triggered a significant increase in levels of KAT6A mRNA at 24 h and protein at 72 h. Furthermore, an overall upregulation of KAT6A after TBI was associated with greater injury severity in a time-dependent manner. Conclusions: Post-traumatic hypothermia plays a key role in the regulation of KAT6A expression and thus may at least partially explain the phenotype of post-traumatic temperature in secondary injury after TBI.

Abstract Fractional frequency transmission is a promising solution to offshore wind power integration. This paper proposes a new grid integration scheme of fractional frequency offshore wind power system (FFOWPS) based on Y‐connected modular multilevel converter (Y‐MMC). To get better power quality, a novel Y‐MMC modelling and control method considering frequency leakage is presented. Besides, in order to achieve satisfactory fault ride‐through (FRT) performance for FFOWPS, this paper proposes a novel FRT strategy. The strategy makes use of the onshore grid voltage and offshore grid frequency droop control to coordinately control the power of Y‐MMC and wind turbines. This strategy achieves power balance on both sides of Y‐MMC through coordinated control, thereby suppressing the increase of DC capacitor voltage during faults. It is also able to support the grid by injecting reactive power during voltage sags. Additionally, a new pitch angle control algorithm is designed to keep the balance between input mechanical power and output active power of wind turbines during FRT, avoiding the rapid rise of rotor speed. The simulation results in MATLAB/Simulink demonstrate good performance of FFOWPS during wind speed variations and validate the effectiveness of the proposed frequency leakage suppression strategy and FRT strategy.

Vitamin C (VC) can greatly enhance the quality properties of dough and steamed bread in the food field. However, there are few studies on the interaction between VC and gluten, and the mechanism of VC influencing the foaming capacity, emulsifiablity, and dynamic viscosity of gluten is not clear. In this study, different content of VC (0, 1%, 2%, 3%, 4% and 5%) was added to gluten to obtain VC-gluten dough samples (CK, GV1, GV2, GV3, GV4 and GV5), and the properties of the VC-gluten dough were determined. Results showed that the increasing VC content lead to increase in the content of high-, medium- and low-molecular weight gluten, suggesting that VC improved the protein solubility of gluten. The G' and G'' values of dough containing VC were higher than those of the control with the increase of scanning frequency. The foaming ability of gluten increased with the increase of VC content. Emulsibility of the dough of GV1 to GV 5 were significantly lower than that of the CK. Furthermore, VC could reduce the number of bubbles in gluten protein, when the VC content was less than 3%. In conclusion, VC might reduce the emulsifying characteristic and emulsifying stability of gluten, increase the solubility of gluten, and improve the dynamic viscosity of gluten dough by changing the content of disulfide bond in gluten. This study hopes to not only improve the functional characteristics of gluten protein, but also provide the basis for future development and improvement of VC-enriched health foods.

BackgroundWork addiction (WA), which can impair personal relationships, engagement in recreational activities, and/or health, is a behavioral addiction. A tool for the early detection of WA in China is needed.ObjectiveThe aim of this study was to develop and determine the validity and reliability of a Chinese version of the Bergen Work Addiction Scale (C-BWAS).MethodsTwo hundred social workers who provided post-discharge services for adolescents with non-suicidal self-injury (NSSI) were enrolled in this study. The construct validity of the C-BWAS was assessed by confirmatory factor analysis (CFA). Criterion validity was assessed by conducting Pearson correlation analyses of C-CWAS scores with Hamilton Depression Scale (HAM-D) and Hamilton Anxiety Scale (HAM-A) scores. Cronbach’s α and the intra-class correlation coefficient (ICC) were used to evaluate the reliability of the C-BWAS.ResultsCFA confirmed a one-dimensional structure of the C-BWAS with good construct validity indices [comparative fit index (CFI) = 0.964, Tucker–Lewis index (TLI) = 0.951, root-mean-square error of approximation (RMSEA) = 0.079, and minimum discrepancy Ĉ/degrees of freedom (Cmin/DF) = 0.362]. The standardized regression weights ranged from 0.523 to 0.753. All C-BWAS items loaded on one major factor (loading weights, 0.646–0.943). Coefficients of correlation between C-BWAS scores and HAM-D and HAM-A scores were 0.889 and 0.933, respectively. The Cronbach’s α coefficient and ICC for the instrument was 0.837 and 0.905, respectively.ConclusionThe presently developed C-BWAS showed very good reliability and acceptably validity. It can be employed as a useful tool for assessing WA severity in social workers who provide post-discharge services for adolescents with NSSI.

LncRNA PVT1 has been implicated in numerous pathophysiological processes and diseases, especially cancers. However, the role and mechanism of PVT1 in the tumorigenesis of glioblastoma remain unclear. We investigated the alteration of PVT1 and its key functions in glioblastoma. PVT1 was upregulated and associated with poor prognosis in glioblastoma. We demonstrated that PVT1 silencing suppressed cell proliferation, colony formation, and orthotopic xenograft tumor growth. Mechanistic investigations found that PVT1 interacted with TRIM24 directly and increased its protein stability. PVT1 recruited COPS5 to deubiquitinate TRIM24; reciprocally, PVT1 depletion impaired the interaction between COPS5 and TRIM24, resulting in decreased expression of TRIM24. PVT1, TRIM24, and COPS5 coordinately contributed to the activation of STAT3 signaling and malignant phenotype of glioblastoma. Collectively, this study elucidates the essential role of PVT1 in the tumorigenesis of glioblastoma, which provides candidacy therapeutic target for glioblastoma treatment.

Neuroinflammation is a major pathophysiological factor that results in the development of brain injury after cerebral ischemia/reperfusion. Downregulation of microRNA (miR)-455-5p after ischemic stroke has been considered a potential biomarker and therapeutic target for neuronal injury after ischemia. However, the role of miR-455-5p in the post-ischemia/reperfusion inflammatory response and the underlying mechanism have not been evaluated. In this study, mouse models of cerebral ischemia/reperfusion injury were established by transient occlusion of the middle cerebral artery for 1 hour followed by reperfusion. Agomir-455-5p, antagomir-455-5p, and their negative controls were injected intracerebroventricularly 2 hours before or 0 and 1 hour after middle cerebral artery occlusion (MCAO). The results showed that cerebral ischemia/reperfusion decreased miR-455-5p expression in the brain tissue and the peripheral blood. Agomir-455-5p pretreatment increased miR-455-5p expression in the brain tissue, reduced the cerebral infarct volume, and improved neurological function. Furthermore, primary cultured microglia were exposed to oxygen-glucose deprivation for 3 hours followed by 21 hours of reoxygenation to mimic cerebral ischemia/reperfusion. miR-455-5p reduced C-C chemokine receptor type 5 mRNA and protein levels, inhibited microglia activation, and reduced the production of the inflammatory factors tumor necrosis factor-α and interleukin-1β. These results suggest that miR-455-5p is a potential biomarker and therapeutic target for the treatment of cerebral ischemia/reperfusion injury and that it alleviates cerebral ischemia/reperfusion injury by inhibiting C-C chemokine receptor type 5 expression and reducing the neuroinflammatory response.

Much recent researches have demonstrated that the quality of freshly-harvested wheat could be improved during postharvest maturation by determinating the rheological properties. However, this process is time-consuming and complex. This study aimed to provide a rapid and convenient method for predicting wheat quality during postharvest maturation by use of GlutoPeak device. Farinograph and Extensograph were used to determine the rheological properties of four wheat samples (WT1, WT2, WT3, WT4) stored under different conditions (WT1: 15 °C, 50% RH; WT2: 20 °C 65% RH; WT3: 28 °C 75% RH; WT4: 35 °C 85% RH) for a total of 10 weeks, and GlutoPeak test was used to determine the gluten aggregation properties of the four samples. Correlation analysis was also conducted between the rheological properties and the gluten aggregation properties. Results of rheological properties showed that all Extensographic properties (dough extensibility, resistance, maximum resistance and area) of the four samples increased along with the storage time, and the Farinographic properties (water absorption, dough development time, dough stability time, and farinograph quality number (FQN)) had the same tendency, indicating that the rheological properties were improved considerably with storage time extending. The GlutoPeak curves revealed that Peak Maximum Time (PMT), Brabender Equivalents Maximum (BEM) and Energy to Maximum Torque (EnMT) of wheat flour of the four samples varied greatly, particularly the PMT and EnMT of the samples WT3 and WT4 increased remarkably. Results of correlation analysis showed that EnMT had significant correlation with water absorption and area (P

BackgroundBorderline personality disorder (BPD) is characterized by behavioral patterns that promote suffering in many adolescents and their guardians. Currently, early diagnosis of BPD mainly depends on the effective assessment of pathological personality traits (i.e., borderline personality features) and using the indicated scales. The Borderline Personality Features Scale for Children-Short Form (BPFSC-SF) is widely used and the introduction of a Chinese version of the BPFSC-SF, can improve the diagnosis and prognosis of Chinese patients with BPD.ObjectiveThe aim of the present study was to assess the validity and reliability of the Chinese version of the BPFSC-SF.Method120 adolescents with BPD were enrolled in the present study and completed the BPFSC-SF and the Personality Belief Questionnaire-Short Form (PBQ-SF) assessments. Confirmatory factor analysis (CFA) was used to test assessment validity. Test-retest correlations and the Cronbach's α coefficients were used to determine reliability.ResultsCFA analysis identified primary factors of BPFSC, with each item ranging from 0.597~0.899. The Spearman rank correlation coefficient was 0.877 between CL-BFSFC-SF and the state vs. trait loneliness scale. The Cronbach's α of the scale was 0.854 in the clinical group. The test-retest reliability correlation coefficient (interclass correlation coefficients.ICC) was 0.937.ConclusionThe Chinese version of BPFSC-SF is a valid and reliable tool for adolescent Chinese patients with BPD.

Abstract Enlarging the speed range of wind turbines is an effective way to increase power production in low‐frequency band wind which contains more energy and is very challenging for DFIG‐based wind energy conversion system (WECS). The analysis shows that current controllability of the converter is the main factor limiting bidirectional speed range extension (BSRE). This problem can be solved by increasing dc‐bus voltage, but a constant and high dc‐bus voltage will increase the electrical stress and switching losses of the converter. This paper proposed a dynamic minimum dc‐bus voltage (DMDCV) technique in which the dc‐bus voltage can automatically adjust to enable the back‐to‐back voltage source converter to work in linear modulation mode at its minimum value, thus supporting BSRE while also achieving multiple goals including low electrical stress and low switching losses. Two implementation methods of DMDCV with and without modulation depth loop are proposed and discussed. The co‐simulation results verified the feasibility of DMDCV and the advantages of BSRE in improving power generation.

Alterations in the global brain gray matter volume (gGMV) and global functional connectivity density (gFCD) play a pivotal role in the cognitive impairment and further deterioration in schizophrenia. This study aimed to assess the correlation between alterations in the gGMV and gFCD at baseline (ΔgGMV and ΔgFCD), and the subsequent alterations of cognitive function in schizophrenia patients after 2-year antipsychotic treatment. Global-brain magnetic resonance imaging scans were acquired from 877 drug-naïve, first-episode schizophrenia patients at baseline and after two years of antipsychotic treatment with adequate dosage and duration, and 200 healthy controls. According to ΔgGMV at baseline, schizophrenia patients were divided into mild, moderate, and severe alteration groups. The MATRICS consensus cognitive battery and Global Deficit Score (GDS) were used to assess cognitive impairment. We found that ΔgGMV and ΔgFCD at baseline were significantly correlated with the severity of the cognitive deterioration (ΔGDS). The correlation coefficient indicated a significant positive correlation between baseline ΔgFCD and subsequent cognitive deterioration, with a relatively stronger relation in the mild alteration group (r = 0.31). In addition, there was a significant positive correlation between baseline ΔgGMV and subsequent cognitive deterioration, with a stronger relation in the moderate and severe alteration groups (r = 0.303; r = 0.302, respectively). Our results showed that ΔgGMV and ΔgFCD are correlated with the severity of cognitive deterioration after completion of a 2-year antipsychotic treatment in schizophrenia patients. These findings suggest that baseline alterations in gGMV and gFCD hold potential for predicting subsequent cognitive decline in schizophrenia.

Although epidemiological studies suggest that periodontitis is tightly associated with ischemic stroke, its impact on ischemic stroke and the underlysing mechanisms are poorly understood. Recent studies have shown that alteration in gut microbiota composition influences the outcomes of ischemic stroke. In the state of periodontitis, many oral pathogenic bacteria in the saliva are swallowed and transmitted to the gut. However, the role of periodontitis microbiota in the pathogenesis and progression of ischemic stroke is unclear. Therefore, we hypothesized that the periodontitis salivary microbiota influences the gut immune system and aggravates ischemic stroke. Mice receiving gavage of periodontitis salivary microbiota showed significantly worse stroke outcomes. And these mice also manifested more severe neuroinflammation, with higher infiltration of inflammatory cells and expression of inflammatory cytokines in the ischemic brain. More accumulation of Th17 cells and IL-17+ γδ T cells were observed in the ileum. And in Kaede transgenic mice after photoconversion. Migration of CD4+ T cells and γδ T cells from the ileum to the brain was observed after ischemic stroke in photoconverted Kaede transgenic mice. Furthermore, the worse stroke outcome was abolished in the IL-17A knockout mice. These findings suggest that periodontitis salivary microbiota increased IL-17A-producing immune cells in the gut, likely promoted the migration of these cells from the gut to the brain, and subsequently provoked neuroinflammation after ischemic stroke. These findings have revealed the role of periodontitis in ischemic stroke through the gut and provided new insights into the worse outcome of ischemic stroke coexisting with periodontitis in clinical trials.

The rapid growth of fossil fuels and the aggravation of emission pollution can be improved by the green and diversified energy structure of road transport vehicles. In this article, Cui–Lawson model is first introduced to analyse the change trend of pure electric vehicle, hybrid electric vehicle, gas–fuel vehicle, fuel cell vehicle, biofuel vehicle and traditional vehicle in the next 50 years. Considering the climate, environment and economic development of each region, the future ownership of the above six models was studied by region. Moreover, the climate and topography affect the developing trend strongly. The ownership of traditional automobile is more than other kinds of vehicles until 35 and 40 years in Xibei and Dongbei regions for the cold temperature.

The aim of this study was to analyze the physicochemical and structural characteristics of the Venn components of wheat gliadin to provide theoretical basis of gliadin for processing in dough and Chinese steamed bread. Eight Venn components, Gli-8, Gli-9, Gli-10, Gli-11, Gli-12, Gli-13, Gli-14, and Gli-15, were extracted from wheat gliadin based on their solubility. The results of physicochemical characteristics showed that the differences in the contents, TDS, electrical conductivity, particle size and zeta potential of Venn components were significant, respectively. The content of Gli-15 in gliadin was the highest, and the content of Gli-9 was the lowest. The TDS value of Gli-9 was the highest (336.0), and the TDS value of Gli-15 was the lowest (52.0). The electrical conductivity of Gli-9 was the highest, which was 7.54 times the lowest value of Gli-11. The zeta potential of Gli-9 was −25.2 mV, and the zeta potential of the Gli-15 was −7.64 mV. However, the difference in the pH values was not significant. The results of UV spectrum and FTIR analysis showed that the secondary structures of the Venn components had significant differences. The results of the XRD patterns indicated that the Venn components might not be a single substance. The results of CLSM images implied that the molecular interactions among the components were varied. Hence, the results could provide research materials and basic data for deep processing and utilization of gliadin. Keywords: Wheat gliadin, Venn components, Physicochemical properties, Structural characteristics

Imbalanced classification using deep learning has attracted much attention in intelligent fault diagnosis of machinery. However, the existing methods use individual deep neural network to extract features and recognize the health conditions under imbalanced dataset, which may easily over-fit the mechanical data and affect the diagnosis accuracy. To deal with this problem, this paper takes the advantages of ensemble learning and proposes an ensemble convolutional neural network (EnCNN) for the intelligent fault diagnosis for machines under imbalanced data. In the proposed method, a convolutional neural network with the input of multi-sensor signals is used as the base classifier. Firstly, the mechanical imbalance dataset is first split into balanced training subsets through under-sampling strategy, and each subset is used to train a base classifier. Then the weight coefficients of each trained base classifier are calculated by G-mean score and anomalous base classifiers are screened using classifier selection. Finally, the base classifiers are integrated into EnCNN through weighted voting strategy. The proposed EnCNN is validated by the imbalanced dataset collected from a machinery fault test bench. By comparing with the related methods, the superiority of EnCNN is verified in intelligent fault diagnosis of machines under imbalanced data.

Deep learning has been applied in intelligent fault diagnosis of machines since it trains deep neural networks to simultaneously learn features and recognize faults. In the intelligent fault diagnosis methods based on deep learning, feature learning and fault recognition are achieved by solving a multi-class classification problem. The multi-class classification, however, has not considered the relationships of fault labels, leading to two weaknesses of these methods. One is that it cannot ensure to learn the correlated features for related faults and the other is that it cannot handle missing label problem. To overcome these weaknesses, we introduce a concept of multi-label classification into intelligent fault diagnosis and propose a deep multi-label learning framework called multi-label convolutional neural network (MLCNN). MLCNN builds the relationship between the labels, and thus it is able to learn the correlated features from mechanical vibration signals and be well trained using the samples with missing labels. A motor bearing diagnosis case and a compound fault diagnosis case are used to verify the proposed method, respectively. The results show that the relationships between features are learned by MLCNN, and the classification accuracies of MLCNN are higher than traditional methods when the missing label problem occurs.

Optical fiber composite low voltage cable (OPLC) is an optimized way of carrying out the function of supplying electrical power and communication signals in a single cable. In this paper, the temperature and stress distribution in OPLC cable is analyzed by using the finite element method as the current increases to maximum capacity. The increase of temperature and stress are the two main factors that affect the additional attenuation in optical fiber. This additional attenuation can be reduced by selecting the optimal heat resistant layer for the optical unit that limits the increase of temperature and stress at the optical fiber. The analysis is carried out for three different kinds of materials by using the finite element method FEM and among them, thermoplastic elastomer TPE is chosen as a heat resistant layer as it restricts the temperature and stress at rated current of 92 A to the minimum values of 69°C and 7.90 × 107 N/m2 respectively. The OPLC cable with TPE as a heat resistant material for the optical unit is put in the experimental setup to analyze the temperature and stress increase inside the cable in real-time using the BOTDA analyzer at normal and under overload condition and compared with the simulation results to verify the correct selection of optimal heat resistant layer for optical unit.

Neuropsychiatric disorders represent a set of severe and complex mental illnesses, and the exact etiologies of which are unknown. It has been well documented that impairments in the early development of the brain contribute to the pathogenesis of many neuropsychiatric disorders. Currently, the diagnosis of neuropsychiatric disorders largely relies on subjective cognitive assessment, because there are no widely accepted biochemical or genetic biomarkers for diagnosing mental illness. Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNA (ncRNA) with a closed-loop structure. In recent years, there have been tremendous advances in our understanding of the expression profiles and biological roles of circRNAs. In the brain, circRNAs are particularly enriched and are expressed more abundantly in contrast to linear counterpart transcripts. They are highly active at neuronal synapses. These features make circRNAs uniquely crucial for understanding brain health, disease, and neuropsychiatric disorders. This review focuses on the role of circRNAs in early brain development and other brain-related processes that have been associated with the development of neuropsychiatric disorders. In addition, we discuss the potential for blood or cerebrospinal fluid circRNAs to be used as novel biomarkers in the early diagnosis of neuropsychiatric disorders. The findings reviewed here may provide new insight into the pathological mechanisms underlying the onset and progression of neuropsychiatric disorders.

The design of gradient coils is sometimes perceived as complex and counterintuitive. However, a current density is connected to a stream function in fact by a simple relation. Here we present an intuitive open source code collection to derive stream functions from current densities on simple surface geometries. Discrete thin wires, oriented orthogonally to the main magnetic field direction are used to describe a surface current density. An inverse problem is solved and stream functions are derived to find coil designs in the current and stream function domains. The flexibility of the design method is demonstrated by deriving gradient coil designs on several different surface topologies. This collection is primarily intended for teaching, as well as for demonstrating all gradient coil design steps with openly available software tools.

β-Conglycinin, the main component of 7S globulin in soybean protein, is also a key soybean antigen protein that causes allergic reactions. Extrusion technologies have received considerable attention as a method for modifying soybean protein allergens. This study investigated the changes in β-conglycinin structure and antigenicity upon extrusion. Isoelectric precipitation, ammonium sulfate precipitation, and sepharose CL-6B gel filtration were used to isolate and purify β-conglycinin from soybean powder, and single-factor and orthogonal tests were used to study the effects of water content, extrusion temperature, screw rotation speed, and feeding speed on the antigenicity of β-conglycinin after extrusion. Fourier transform infrared spectrometry (FTIR) was then employed to analyze the structure of β-conglycinin after extrusion under the optimal conditions determined by the orthogonal test. The results showed that extrusion significantly reduced the antigenicity of β-conglycinin (P feeding speed > screw rotation speed > water content. The optimal conditions were temperature at 130 °C, screw rotation speed at 140 r/min, and feeding speed at 35 g/min. Under these conditions, the contents of α-helix, β-pleated sheet, and β-turn structures in β-conglycinin were significantly reduced (P

Abstract The function of nuclear receptor corepressor 1 (NCoR1) in cardiomyocytes is unclear, and its physiological and pathological implications are unknown. Here, we found that cardiomyocyte‐specific NCoR1 knockout (CMNKO) mice manifested cardiac hypertrophy at baseline and had more severe cardiac hypertrophy and dysfunction after pressure overload. Knockdown of NCoR1 exacerbated whereas overexpression mitigated phenylephrine‐induced cardiomyocyte hypertrophy. Mechanistic studies revealed that myocyte enhancer factor 2a (MEF2a) and MEF2d mediated the effects of NCoR1 on cardiomyocyte hypertrophy. The receptor interaction domains (RIDs) of NCoR1 interacted with MEF2a to repress its transcriptional activity. Furthermore, NCoR1 formed a complex with MEF2a and class IIa histone deacetylases (HDACs) to suppress hypertrophy‐related genes. Finally, overexpression of RIDs of NCoR1 in the heart attenuated cardiac hypertrophy and dysfunction induced by pressure overload. In conclusion, NCoR1 cooperates with MEF2 and HDACs to repress cardiac hypertrophy. Targeting NCoR1 and the MEF2/HDACs complex may be an attractive therapeutic strategy to tackle pathological cardiac hypertrophy.

To investigate a comparative evaluation of the gluten polymerization properties at different oil contents during the extrusion processing, the electrophoretic profiles of the gluten, free sulfhydryl (SH) compounds, the secondary structure of gluten, glutenin macropolymer contents and gluten network were measured. Five gluten samples were formulated by adding different oil contents. The low molecular weight contents of gluten decreased as well as the high molecular weight contents increased during the extrusion processing. The free SH of gluten at 8 or 10% oil content drops significantly to a minimum. The β-sheets contents of gluten have significantly difference between the treatments and control, except for 15 and 20% oil content treatments. Confocal laser scanning microscopy of mixed glutens correlated to the degree of oil contents with the gluten in the bi-continuous gluten network.

In this study, we revealed the differential proteins from the wheat endosperms using proteomic analysis and investigated their surface properties. The pattern of the polypeptides obtained from the Yangmai-15 and Yangmai-16 wheat varieties were compared using two-dimensional polyacrylamide gels. In addition, we compared the characteristics of the grain such as grain hardness, protein content, wet gluten, dough development time, dough stability, gliadin and glutenin contents between Yangmai-15 and Yangmai-16, and the results were significantly different. Notably, 216 and 197 protein spots were separated from Yangmai-15 and Yangmai-16, respectively. The isoelectric points of the identified proteins ranged from 4 to 10 and the molecular weights of proteins varied from 10 to 100 kDa. Further, 21 and 8 specific differential protein spots were identified from the flour of Yangmai-15 and Yangmai-16, respectively. The surface properties of identified peptides consisted of hydrophobic or hydrophilic residues, as well as randomly scattered residues. The proteomic analysis of the wheat endosperms provides a novel insight into the biochemical basis for the differences in physicochemical properties between the soft and hard wheat varieties. Keywords: Soft and hard wheat, Proteome, Peptides surfaces, Endosperm proteins

The debittering effect of extracellular enzymes from Bacillus subtilis ACCC 01746 was studied using soybean meal as a substrate for solid-state fermentation (SSF). Results showed that B. subtilis produces proteases and carboxypeptidase in the early stage of SSF (0–8 h). Proteases are dominant and can hydrolyze the soybean protein into long-chain peptides with mild bitterness. Carboxypeptidase production is dominant at 8–16 h SSF, at which point soybean protein is further hydrolyzed and bitterness is enhanced. The strain then produces additional carboxypeptidase after 16 h, and bitterness is reduced. We compared the amino acid composition of the hydrolysates from soybean protein isolates to that of the fermented liquid of SSF. In the hydrolysates from soybean protein isolates that exhibit strong bitterness, 62.81% of amino acids are hydrophobic and occur in the form of peptides. In the fermented liquid from soybean meal, 16.22% of amino acids are hydrophobic and are mainly present in the form of free amino acids. The bitterness of fermented soybean hydrolysate is reduced from 5 to 0 when fermented for 24 h, suggesting that B. subtilis can effectively reduce bitterness, possibly due to the carboxypeptidase. Enzyme analysis shows that B. subtilis excretes carboxypeptidase during growth. The amino acids phenylalanine, alanine, tyrosine, and leucine at the C-terminal of the soybean bitter peptides in hydrolysates are cleaved in the presence of carboxypeptidase, resulting in complete debitterness. Keywords: Solid-state fermentation, Bacillus subtilis, Protease, Debitterness, Soybean meal

The tooth surface of the spur face gear is a kind of complex space curved surface, in order to realize the batch machining of complex space curved surface products with difficult cutting materials, the main technology of electrolytic machining is mainly used at present. Considering that electrolytic machining has some problems such as low efficiency of cathode design and difficult to guarantee the design accuracy in the machining of complex dissimilar surface products, an intelligent design method of cathode profile based on the characteristics of standard cathode is presented. Firstly, based on complex tooth surface grid planning principle, the coordinate of each sampling tooth surface is calculated by section lofting method. Secondly, by analyzing the curvature radius of each tooth surface sampling point, the design scheme of the corresponding cathode tool profile is constructed based on the theory of electrolytic machining equilibrium gap theory. Finally, using the GUI human-computer interface in Matlab, the intelligent cathode profile design system for spur face gear is constructed. Meanwhile the experimental shows that the machining accuracy of the cathode surface designed by the system is up to IT8.

Abstract Background Glioblastoma multiform (GBM) is a devastating brain tumor with maximum surgical resection, radiotherapy plus concomitant and adjuvant temozolomide (TMZ) as the standard treatment. Diverse clinicopathological and molecular features are major obstacles to accurate predict survival and evaluate the efficacy of chemotherapy or radiotherapy. Reliable prognostic biomarkers are urgently needed for postoperative GBM patients. Methods The protein coding genes (PCGs) and long non-coding RNA (lncRNA) gene expression profiles of 233 GBM postoperative patients were obtained from The Cancer Genome Atlas (TCGA), TANRIC and Gene Expression Omnibus (GEO) database. We randomly divided the TCGA set into a training (n = 76) and a test set (n = 77) and used GSE7696 (n = 80) as an independent validation set. Survival analysis and the random survival forest algorithm were performed to screen survival associated signature. Results Six PCGs (EIF2AK3, EPRS, GALE, GUCY2C, MTHFD2, RNF212) and five lncRNAs (CTD-2140B24.6, LINC02015, AC068888.1, CERNA1, LINC00618) were screened out by a risk score model and formed a PCG-lncRNA signature for its predictive power was strongest (AUC = 0.78 in the training dataset). The PCG-lncRNA signature could divide patients into high- risk or low-risk group with significantly different survival (median 7.47 vs. 18.27 months, log-rank test P