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Early comprehensive assessment and early intervention of vascular disease, and the life-time maintenance of vascular health are the key to effectively preventing death and disability in end-stage of heart, brain, kidney and peripheral vascular events. Based on this concept, it is necessary to establish a professional clinical discipline of "vascular medicine" which is based on the systemic vascular bed, with measures on prevention, treatment, rehabilitation and intellectualized and digital vascular health management throughout the life cycle for different vascular lesions and different degree of vascular injury. The aim of the establishment of Beijing Vascular Health Stratification (BVHS) is to give a comprehensive and dynamic assessment of vascular health based on the concept of vascular medicine, to conduct individualized analysis of the results, to classify the degree of injury on vascular structure and function, to carry out individualized intervention, and eventually achieve targeted precise prevention and management, establish newly intellectualized and digital vascular health management medical model in China, for effectively reducing the incidence of cardiovascular events.对血管早期病变的综合评估和早期干预，血管健康的全生命周期维护是有效预防致死致残心、脑、肾和周围血管事件的关键，基于这一理念，需要建立“血管医学”专业临床学科，以全身血管床为核心，对不同部位血管病变和不同病变程度的人群，进行预防、治疗以及系统康复，并进行全生命周期的血管健康智慧化和数字化管理。北京血管健康分级法（BVHS）提出的目的就是根据血管医学的理念，对血管健康给予综合动态评估，并将其结果进行个体化分析，将血管结构及功能病变程度综合分级，以对各危险等级人群进行个体化精准干预，实现针对性地预防和管理，建立全新的智慧化数字心脏和血管健康医学模式，有效降低心脑血管事件的发生。.

The major objective of this review was to compare the diagnostic accuracy of ultrasound in confirming tracheal intubation to the standard methods of confirmation in the intensive care unit (ICU).This systematic review and meta-analysis of observational studies was conducted from inception to July 2022. We included studies that compared the diagnostic accuracy of ultrasound-detected tracheal intubation to that of the gold standard diagnostic technique performed in adult patients who underwent tracheal intubation as part of any procedure. We searched the following electronic databases for published studies: PubMed, EMBASE, Cochrane Central, and Web of Science. Risk of bias was assessed using a standard procedure based on the Quality Assessment of Diagnostic Accuracy Studies-2 criteria. The results were analyzed using the RevMan or Meta-Disc software to determine the adequacy and conclusiveness of the available evidence.Five studies that included 344 patients met the inclusion criteria. Pooled sensitivity was 0.96 (95% confidence interval (CI) (0.92-0.98) and 1.00 (95% CI: 0.97-1.00), respectively. Furthermore, the diagnostic odds ratio of ultrasonography was 311.25 (95% CI: 63.77-1,519.22), which was confirmed by a summary receiver operating characteristic curve with an area under the curve of 0.98.Ultrasonography has high sensitivity and specificity, is a valuable adjunct for confirming tracheal intubation in the ICU and should be performed when capnography is unavailable or unreliable.

Acute respiratory distress syndrome (ARDS) is a critical disease commonly found in many clinical cases, with a mortality rate of approximately 50%. Early diagnosis and intervention are important for improving ARDS prognosis. In this study, the applications of lung ultrasound in ARDS diagnosis and assessment are reviewed to clarify its key clinical values and application prospects.According to the standard diagnosis of ARDS based on the Berlin definition, CXR or CT examination should be conducted. However, both the blurred images of the former, as well as the inconvenience and high risks of the latter, impose restrictions on their application in critically ill patients.Lung ultrasound was shown to improve safety, effectiveness, lacked radiation, can be performed bedside, and offers dynamic functionality.It may be a suitable approach to replace or complement traditional imaging examinations with lung ultrasound.

Enteral nutrition (EN) is the first-choice nutritional support, as it is more in line with normal physiological processes. During EN, the major goals to achieve include accurate confirmation of the feeding tube position, monitoring the gastric residual volume, assessing gastrointestinal motility, and monitoring the nutritional status of patients. With rapid development in technology, point-of-care ultrasound (POCUS) has become a more convenient and effective technical tool for monitoring critically ill patients receiving EN. In this review, we have summarized and discussed the value of POCUS in the implementation, monitoring, and evaluation of EN therapy to provide a reference for nutritional support of critically ill patients in critical care settings.This is a narrative review. A literature search for Scopus-indexed articles was performed randomly using PubMed and MEDLINE databases as the primary sources. No specific term was used for the search.POCUS can be used for positioning of nasogastric and nasointestinal tubes, evaluation of gastric residuals and gastrointestinal motility as well as monitoring of nutritional status.POCUS is a real-time, highly repeatable, radiation-free, and non-invasive visual inspection technique, with high application value in assessing the nutritional status of patients receiving EN and guiding the development of further nutritional treatment plans. It is an important diagnostic and monitoring tool that can be used by the clinicians in the ICU.

With the progress of medical imaging technology and the accumulation of experience, dual-energy CT has moved from simple scientific research to clinical application. In the imaging of abdominal tumors, dual-energy CT has obvious advantages over conventional CT in improving the diagnostic performance, reflecting the pathological characteristics of malignant tumors and evaluating the therapeutic effect. This paper briefly describes the classification of dual-energy CT, the current research status of this technology in abdominal malignant tumors, and puts forward the challenges and application traps faced by dual-energy CT technology, in order to promote the clinical generalization and application of this technology.随着医学影像检查技术的进步与经验的积累，双能量CT已从单纯科学研究走向临床应用。在腹部肿瘤成像中，双能量CT在提高诊断性能、反映恶性肿瘤病理特征和评估治疗效果等方面较常规CT具有明显优势。本文简述了双能量CT的分类、目前该技术在腹部恶性肿瘤的研究现状，提出了双能量CT技术面临的挑战与应用陷阱，以期推进该技术的临床普及应用。.

To investigate the optimal androgen concentration for culturing Hetian sheep wool follicle and to detect effects of androgen concentration on wool follicle cell proliferation and apoptosis using immunofluorescence labeling and real-time quantitative fluorescence determinations of wool keratin-associated protein gene expression levels. Wool follicles were isolated by microdissection and wool follicles and skin pieces were cultured in various concentrations of dihydrotestosterone (DHT) in culture medium. Next, daily lengthwise growth measurements of wool follicles were obtained using a microscopic micrometer. Cultured Hetian wool follicles were stained using the SACPIC method to reveal wool follicle structure, while sheep skin slices were used to observe cell proliferation by immunostaining and cell apoptosis using the TUNEL method. At the molecular biological level, keratin-associated protein (Kap) gene expression was studied using wool follicles cultured for various numbers of days in vitro. Effects of androgen concentrations on Hetian wool follicle growth and development were experimentally studied. EdU proliferation assays revealed that androgen promoted cell proliferation within wool follicle dermal papillae. TUNEL apoptosis detection demonstrated that androgen treatment could delay cell apoptosis. Quantitative reverse transcription polymerase chain reaction (qPCR) results demonstrated that gene expression level patterns of Hetian mountain sheep super-high sulfur protein. Kap1.1, KIF1.2, Kap2.12 and Kap4.2 gene expression level of the mountainous experimental group was significantly higher than plains Hetian sheep. An androgen concentration of 100 nM can promote the growth of Hetian wool follicle cells in vitro, resulting in overexpression of some genes of the Kap family. Resumo Investigar a concentração ideal de andrógenos em cultura de folículos pilosos de carneiro Hetiano e detectar os efeitos da concentração de andrógenos na proliferação e apoptose de células foliculares, por meio de imunofluorescência e de determinação quantitativa, em tempo real, da fluorescência dos níveis de expressão gênica de proteína associada à queratina. Folículos pilosos foram isolados por microdissecção, e folículos de lã e pedaços de pele foram cultivados em várias concentrações de di-hidrotestosterona (DHT) em meio de cultura. Em seguida, medições diárias de crescimento longitudinal dos folículos capilares foram obtidas usando um micrômetro microscópico. Folículos de lã cultivados de Hetianos foram corados pelo método SACPIC para revelar a estrutura do folículo piloso, enquanto fatias de pele de carneiro foram usadas para observar a proliferação celular por imunocoloração e apoptose celular por meio do método TUNEL. Em âmbito da biologia molecular, a expressão gênica da proteína associada à queratina (Kap) foi estudada usando folículos capilares cultivados por vários dias, in vitro. Os efeitos das concentrações de andrógenos no crescimento e desenvolvimento dos folículos de lã de Hetianos foram estudados experimentalmente. Ensaios de proliferação de EdU revelaram que o andrógeno promoveu a proliferação celular dentro das papilas dérmicas do folículo piloso. A detecção de apoptose por TUNEL demonstrou que o tratamento com andrógeno poderia atrasar a apoptose celular. Os resultados da reação em cadeia da polimerase transcrição reversa quantitativa (qPCR) demonstraram que os padrões de expressão gênica da proteína de enxofre Kap1.1, KIF1.2, Kap2.12 e Kap4.2 foram significativamente maiores no grupo de ovinos Hetianos de montanha. Uma concentração de androgênio de 100 nM pode promover o crescimento de células foliculares de lã de Hetianos in vitro, resultando na superexpressão de alguns genes da família Kap.

Anaplastic lymphoma kinase-positive (ALK+) and ROS proto-oncogene 1 (ROS1)-positive (ROS1+) lung cancers have been reported to be associated with an elevated risk of thromboembolic events. This study aimed to assess the long-term risk of developing thromboembolism (TE) in ROS1+ lung cancer and to compare it with other oncogenic drivers in the Asian population.We retrospectively enrolled a cohort of ROS1+ lung adenocarcinoma in a medical center in Taiwan and a comparison cohort of ALK+ and epidermal growth factor receptor-positive (EGFR+) lung cancers. Venous and arterial TEs were identified throughout the cancer course, and the incidence rate was calculated.We enrolled 44 ROS1+, 98 ALK+, and 168 EGFR+ non-small-cell lung cancer (NSCLC) patients. A total of 11 (25%), 36 (36.7%), and 38 (22.6%) patients in the ROS1, ALK, and EGFR cohorts, respectively, were diagnosed with thromboembolic events throughout the follow-up course of the disease (P = 0.042). The incidence rates were 99.0, 91.9, and 82.5 events per 1000 person-years for the ROS1, ALK, and EGFR cohorts, respectively. The majority of thrombosis events in the ROS1 (91.6%) and ALK (85.4%) cohorts were venous. On the contrary, 43.2% of thromboembolic events were arterial in the EGFR cohort. A higher proportion of thromboembolic events were noted during cancer diagnosis in the ROS1 cohort (36.3%) than in the ALK (16.7%) and EGFR (10.5%) cohorts. The stage was the only clinical variable associated with thromboembolic risk. There was a significant difference in survival between patients with and without TE in the EGFR cohort, but not in the ALK and ROS1 cohorts.Although ROS1+ and ALK+ NSCLCs had a higher cumulative incidence of TE than EGFR+ NSCLC, the person-year incidence rates were similar among the three groups. EGFR-mutated NSCLC had more arterial events. Nevertheless, ALK+ lung cancer had higher venous events than EGFR-mutated lung cancer.

It is well known that phloem is essential for transporting proteins as long-distance signals. In this study, a proteomic approach was carried out to identify proteins accumulated in phloem exudates at the pre-floral induction (PFId) stage, at the floral induction (FId) stage, and at the floral initiation (FIn) stage. As a result, 45 phloem exudate proteins were detected. Six proteins were found at all three stages. Sixteen proteins were specific to the PFId stage, 14 proteins were specific to the FId and FIn stages. From the enriched gene ontology (GO)-terms related to transport, signaling, hormone, and development, 12 transport-related, 5 signaling-related, 10 hormone-related, and 9 development-related proteins were identified. It was found that arginine glycine glycine repeats nuclear RNA binding protein A (RGGA) was specific to the FId stage whereas heat shock protein 90-7, plasma membrane intrinsic protein 1-4, and the homolog protein encoded by At4g27190 were specific to the FIn stage. The relative abundances of sporulation protein F10D13.7 and ATP-dependent binding casette transporter G family member 37 were higher at the FId stage than at the PFId stage, and that of enolase 2 was higher at the FIn stage than at the PFId stage, suggesting that these phloem exudate proteins might act as long-distance signals involved in the transition from vegetative growth to reproductive growth in litchi. This study contributes to the comparative proteomic analysis of plant phloem sap, which will provide insights into proteins involved in floral induction as well as inter-organ communication during development in litchi.

The essential oil from the aerial parts of Lobularia maritima was investigated for its chemical composition, and its repellent and insecticidal efficacy against the grain pests Callosobruchus maculatus, Tribolium castaneum and Sitophilus oryzae. A number of 41 compounds were identified by GC-MS from which azeleonitrile (39.7%), trans-3-pentenenitrile (36.3%) and 4-isothiocyanato1-butene (10.9%) were the most abundant. A fumigant bioassay-guided fractionation of the essential oil constituents led to the isolation of trans-3-pentenenitrile. Its structure was confirmed by EI-MS and NMR techniques. Fumigant effect of the essential oil was strong (LC50 = 7.48 μL/L) on C. maculatum and moderate on S. oryzae and T. castaneum (LC50 = 35.37 and 59.94 μL/L, respectively). trans-3-pentenenitrile showed strong fumigant effect on the three pest species (LC50 = 6.62–8.36 μL/L). Both the oil and trans-3-pentenenitrile showed strong contact effect with LD50 values in the range 4.84–7.81 µg/adult. The oil showed a repellency of 100% on C. maculatus and S. oryzae at concentrations higher than 0.05 and 0.1 nL/cm2 , respectively, and 93% against T. castaneum yet at 0.2 nL/cm2 . trans-3-pentenenitrile also showed 100% repellency against C. maculatus (≥ 0.05 nL/cm2 ), S. oryzae (≥ 0.15 nL/cm2 ) and T. castaneum (0.2 nL/cm2 ). The results in this study indicated that the essential oil of L. maritima is an important source of trans-3-pentenenitrile which can be used in the development of insecticidal agents against the three grain pests. Fil: Wang, H. Y.. Jilin University; China Fil: Zhang, M. Z.. Jilin University; China Fil: Han, X.. Jilin University; China Fil: Cong, J.. Jilin University; China Fil: Wang, S. Q.. Jilin University; China Fil: He, S. L.. Jilin University; China Fil: Wei, D. S.. Jilin University; China Fil: Zhang, Y. B.. Jilin University; China Fil: Qin, Jianchun. Jilin University; China Fil: Sampietro, Diego Alejandro. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Estudios Vegetales. Cátedra de Fitoquímica; Argentina

Clustering as an unsupervised learning method is a process of dividing a data object or observation object into a subset, that is to classify the data through observation learning instead of example learning without the guidance of the prior class label information. Bat algorithm (BA) is a swarm intelligence optimization algorithm inspired by bat's ultrasonic echo localization foraging behavior, but it has the disadvantages of being easily trapped into local minima and not being highly accurate. So an improved bat algorithm was proposed. In the global search, a Gaussian-like convergence factor is added, and five different convergence factors are proposed to improve the global optimization ability of the algorithm. In the local search, the hunting mechanism of the whale optimization algorithm (WOA) and the sine position updating strategy are adopted to improve the local optimization ability of the algorithm. This paper compares the clustering effect of the improved bat algorithm with bat algorithm, flower pollination algorithm (FPA), harmony search (HS) algorithm, whale optimization algorithm and particle swarm optimization (PSO) algorithm on seven real data sets under six different convergence factors. The simulation results show that the clustering effect of the improved bat algorithm is superior to other intelligent optimization algorithms.

Background Patients with diabetes mellitus (DM) are known to be at high-risk for both ischemic and bleeding complications post-percutaneous coronary intervention (PCI). The ischemic benefit vs. bleeding risk associated with extended dual antiplatelet therapy (DAPT) in high-risk “TWILIGHT-like” patients with diabetes mellitus after PCI has not been established. Methods All consecutive high-risk patients fulfilling the “TWILIGHT-like” criteria undergoing PCI were identified from the prospective Fuwai PCI Registry. High-risk “TWILIGHT-like” patients were defined by at least one clinical and one angiographic feature based on the TWILIGHT trial selection criteria. The present analysis evaluated 3,425 diabetic patients with concomitant high-risk angiographic features who were event-free at 1 year after PCI. Median follow-up was 2.4 years. The primary effectiveness endpoint was a composite of death, myocardial infarction, or stroke (termed major adverse cardiac and cerebrovascular events), and primary safety endpoint was clinically relevant bleeding according to the Bleeding Academic Research Consortium types 2, 3, or 5. Results On inverse probability of treatment weighting (IPTW) analysis, prolonged-term (>1-year) DAPT with aspirin and clopidogrel decreased the risk of primary effectiveness endpoint compared with shorter (≤1-year) DAPT (1.8% vs. 4.3%; hazard ratio [HR]IPTW: 0.381; 95% confidence interval [CI]: 0.252–0.576; P0.05). Conclusions In this real-world retrospective analysis of diabetic patients with concomitant high-risk angiographic features who were event-free at 1 year after PCI, extended-term (>1-year) DAPT with clopidogrel and aspirin reduced the risk of MACCE and mortality compared with DAPT discontinuation within 1 year without significant differences in terms of clinically relevant bleeding. As such, long-term DAPT may be considered when contemplating an antiplatelet therapy in high-risk PCI patients with DM for a broader coronary atherothrombotic events protection. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Beijing Municipal Health Commission (Grant No. 2020-1-4032)

Background High thrombotic risk (HTR) and high bleeding risk (HBR) features after PCI can occur in the same patient. The individualized risks of ischemic vs. bleeding events are needed to be considered for determining the optimal duration of DAPT. We aimed to evaluate long-term ischemic and bleeding outcomes in patients who are at both HTR and HBR after DES implantation. Methods All consecutive patients who underwent PCI with DES were prospectively enrolled in Fuwai PCI Registry. HTR criteria based on 2017 ESC DAPT guidelines were defined as: diffuse multivessel diabetic CAD patients, chronic kidney disease, ≥3 stents implanted, ≥3 stents lesions treated, bifurcation with two stents implanted, total stent length >60 mm, or chronic total occlusion. Patients were defined as HBR if they met at least 1 major or 2 minor Academic Research Consortium (ARC)-HBR criteria. The primary ischemic outcome was major adverse cardiac event (MACE), a composite of cardiac death, myocardial infarction, target vessel revascularization and stent thrombosis. Results Among 10,167 patients, 4,430 (43.6%) qualified as HTR. The rate of HBR patients was significantly higher in the HTR group than in the non-HTR group (18.9% versus 12.2%, P Conclusions A combination of ESC-HTR and ARC-HBR may increase the risk of long-term ischemic events, including cardiac mortality, emphasizing the importance of considering the net clinical benefit including high ischemic and bleeding features. Our data suggest that ESC-HTR criteria was useful for stratifying post-PCI patients into risk strata for future ischemic events. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Beijing Municipal Health Commission (Grant No. 2020-1-4032) Kaplan-Meier event rates

Background The long-term clinical outcome after PCI is affected by various clinical and angiographic risk features. The present study was designed to investigate the long-term prognostic impact of risk enhancers and technical aspects as defined by 2020 ESC NSTE-ACS Guidelines for high thrombotic risk (HTR) criteria on the risk of adverse events after PCI. Methods A total of 10,167 patients were enrolled from the Fuwai PCI registry. Risk enhancers and technical aspects were retrospectively assessed according to 2020 ESC NSTE-ACS Guidelines. Risk enhancers were defined as having at least one of the following characteristics: diabetes mellitus requiring medication, history of recurrent MI, any multivessel CAD, peripheral artery disease, premature (60 mm, left main PCI, bifurcation stenting with ≥2 stents implanted, and chronic total occlusion. The primary endpoint was 30-month major adverse cardiac and cerebrovascular events (MACCE, a composite of cardiac death, myocardial infarction [MI], stent thrombosis, any revascularization, and ischemic stroke). Results MACCE occurred in 1188 (11.7%) patients during the follow-up period (median duration: 881 days). Risk enhancers were present in 8,437 patients (83.0%) and was associated with increased 30-month risk for the MACCE (adjusted hazard ratio [adjHR]: 2.11; 95% CI: 1.72–2.60). Technical aspects were present in 3,335 patients (32.8%) and was an independent predictor of MACCE at 30 months (adjHR: 1.32; 95% CI: 1.17–1.49). The risk of MACCE associated with risk enhancers was significantly higher than for technical aspects (2.11 vs. 1.32; relative risk [RR]: 1.60; 95% CI: 1.47–1.75). Results were consistent when risk enhancers and technical aspects were modeled as a continuous variable. Adjusted HRs of MACCE within the 12 months for patients with risk enhancers and technical aspects were 2.35 (95% CI: 1.80–3.07) and 1.50 (95% CI: 1.30–1.73), respectively. Risk enhancers significantly influenced MACCE beyond 12 months (adjHR: 1.78; 95% CI: 1.29–2.46), whereas technical aspects were not associated with very late (12-month to 30-month) MACCE (adjHR: 1.01; 95% CI: 0.82–1.25). Both risk enhancers and technical aspects were not significantly associated with BARC type 2, 3, or 5 bleeding within 12 months and between 12 and 30 months. Conclusions Both risk enhancers and technical aspects of HTR criteria significantly affected long-term ischemic clinical events but not major bleeding in patients undergoing PCI. Risk enhancers appeared to have a greater and more prolonged effect on poor prognosis than technical aspects, suggesting the importance of compliance with guideline-directed medical therapy. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Beijing Municipal Health Commission (Grant No. 2020-1-4032)Chinese College of Cardiovascular Physicians, CS Optimizing Antithrombotic Research Fund (Grant number: BJUHFCSOARF201801-01)

Chronic obstructive pulmonary disease (COPD) represents a chronic inflammatory disorder of the airways induced mainly by cigarette smoking. In the current study, cigarette smoke extract (CSE) was used to develop an in vitro COPD model using human bronchial epithelium (HBE) cells to expound the possible role of microRNA-29b (miR-29b) in COPD. Firstly, miR-29b and interleukin (IL)-22 expression was assessed in serum of 20 healthy non-smokers, 20 healthy smokers and 20 COPD patients as well as CSE-treated HBE cells. Then, miR-29b and IL-22 expression was altered to evaluate their functions in Th17/Treg ratio. miR-29b inhibited Th17/Treg ratio and levels of IL-22; whereas overexpression of IL-22 reversed these trends. Moreover, rescue experiments found that IL-22 neutralized the repressive effects of miR-29b on Th17/Treg ratio and inflammatory response. Finally, we found that miR-29b blocked the JAK/STAT3 pathway in CSE-treated HBE cells. These data highlighted that miR-29bs modulated Th17/Treg imbalance in CSE-induced experimental COPD through inhibition of IL-22-dependent JAK/STAT3 pathway.

Dirac semimetals (DSMs) are classified into different phases based on the types of the Dirac fermions. Tuning the transition among different types of the Dirac fermions in one system remains challenging. Recently, KMgBi was predicted to be located at a critical state that various types of Dirac fermions can be induced owing to the existence of a flat band. Here, we carried out systematic studies on the electronic structure of KMgBi single crystal by combining angle-resolve photoemission spectroscopy (ARPES) and scanning tunneling microscopy/spectroscopy (STM/STS). The flat band was clearly observed near the Fermi level. We also revealed a small bandgap of ~ 20 meV between the flat band and the conduction band. These results demonstrate the critical state of KMgBi that transitions among various types of Dirac fermions can be tuned in one system., 15 pages, 4 figures

To explore the effect of rehabilitation training on cognitive impairment after cerebrovascular accident and its potential mechanism.100 patients of cerebrovascular accident treated in our hospital from August 2018 to August 2019 were selected as the subjects, and 50 patients with physical examination were selected as healthy control group. The patients with cerebrovascular accident were randomly divided into control group (50 patients) and research group (50 patients). The patients in the control group were given routine medication, the patients in research group were given rehabilitation training on the basis of routine drug therapy. The blood samples were collected on admission and 6 months after admission to detect the molecular markers related to inflammation, nerve cell nutrition and function and apoptosis in the serum. The cognitive function was evaluated by scales. We established a rat cerebral ischemia model, compared the differences in the evasive latency, serum CRP, BNDF, Bcl-2, BAX, Glu, NE levels and BNDF, TrkB, pTrkB, JNK levels in hippocampus, amygdala, and prefrontal tissue between model rats after rehabilitation training and model rats without rehabilitation training.On admission, there were no significant differences in the scores of Barthel index (BI), Fugl-Meyer motor function scale (FM), Montreal cognitive assessment scale (MoCA) and mini-mental state examination (MMSE) (p0.05). 6 months later, the above scores and BNDF, Bcl-2, and norepinephrine were significantly higher in the research group (p0.05), while CRP, Bax, 5-HT and glutamate in the research group were significantly lower than those in the control group (p0.05).Rehabilitation training can improve the motor function, mental state and cognitive level of patients, reduce the levels of neurotoxic factors, pro-inflammatory factors and pro-apoptotic factors, and improve the levels of inhibiting apoptotic factors, neurotrophic factors and neurotransmitters. In animal experiments, rehabilitation training can increase BDNF and its activated receptors in hippocampus, amygdala and prefrontal lobe of rats, and decrease JNK of apoptotic protein, suggesting that rehabilitation training may regulate the expression of apoptotic proteins Bcl-2 and Bax by upregulating BDNF and its receptors and acting on JNK pathway, thereby inhibiting cell apoptosis and improving cognitive impairment after cerebrovascular accident.

Magnetic properties and microstructure of melt-spun PrCo5− x − y Fe x C y ( x = 0 and 0.3; y = 0–0.3) ribbons are studied. For PrCo5 ribbons spun at lower wheel speed of 20 m/s, the coexistence of 2:17 phase with magnetic hard 1:5 phase leads to low coercivity of 0.6 kOe. Increasing wheel speed to 40 m/s imroves the coercivity to 3.3 kOe due to the increased volume fraction of 1:5 phase. Interestingly, magnetic properties of PrCo5 ribbons melt spun at 40 m/s ( Br = 6.4 kG, i H c = 3.3 kOe, and ( BH )max = 4.5 MGOe) are improved to Br = 6.1–6.5 kG, i H c = 7.8–13.5 kOe, ( BH )max = 7.3–8.9 MGOe by doping C, and significantly enhanced to Br = 6.3 kG, i H c = 16.1 kOe, and ( BH )max = 9.3 MGOe for C and Fe co-doped PrCo4.6Fe0.3C0.1 ribbons. The structural and thermo-magnetic analysis confirms that the entrance of Fe and part of C into the crystal structure of 1:5 phase leads to the increase of Curie temperature. Doping proper C content not only uniformly refines grain size and, therefore, improves the squareness of demagnetization curve and ( BH )max, but also increases the volume fraction of 1:5 phase, and thus enhances the coercivity. The increased volume fraction of 1:5 phase and the reduced magnetic domain size due to refined microstructure by co-doping Fe and C make PrCo4.6Fe0.3C0.1 ribbons exhibit a high permanent magnetic performance. They are promising candidate materials for making bonded magnets.

The aim of this study was to explore the effects of micro ribonucleic acid (miR)-195 on diabetic nephropathy (DN) rats through targeting Toll-like receptor 4 (TLR4) and inhibiting the nuclear factor-κB (NF-κB) signaling pathway.The model of DN was first successfully established in rats. All rats were randomly divided into six groups, including control group (n=20), model group (n=20), 25 nM miR-195 mimics group (25 nM M group, n=20), 50 nM M group (n=20), 25 nM miR-195 inhibitor group (25 nM I group, n=20), and 50 nM I group (n=20). Urine volume, proteins and inflammatory factors were detected in each group, respectively. Subsequently, macrophages were cultured and transfected in vitro. The mRNA expressions of miR-195 and TLR4 in control group and model groups were determined using fluorescence quantitative polymerase chain reaction (qPCR). The protein expressions of TLR4 and NF-κB in macrophages were determined using Western blotting. Furthermore, the proliferation of macrophages was detected via cell counting kit-8 (CCK-8) assay.Compared with model group, 24-h urine volume, urine protein, creatinine, urea nitrogen, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 levels declined significantly in 25 nM M group and 50 nM M group (p0.05). However, they increased significantly in 25 nM I group and 50 nM I group (p0.05). It could be suggested that miR-195 mimics might relieve the symptoms of DN rats. In kidney tissues in DN, miR-195 was lowly expressed, whereas TLR4 was highly expressed (p0.01). This suggested that there was a negative correlation between the mRNA expressions of miR-195 and TLR4 (r2=0.4836, p=0.0007). After overexpression of miR-195, the protein expression of TLR4 was significantly reduced (p0.01), indicating that miR-195 could negatively regulate the protein expression of TLR4. Besides, the protein expressions of TLR4 and NF-κB in si-TLR4 group were evidently lower than those in NC group (p0.01). Meanwhile, they also had significant differences in si-TLR4 group compared with si-TLR4 + miR-195 inhibitor group (p0.05). The above results demonstrated that the protein expressions of TLR4 and NF-κB in macrophages could be markedly inhibited by si-TLR4, but be promoted by si-TLR4 + miR-195 inhibitor. CCK-8 assay demonstrated that the proliferation ability of macrophages was remarkably weaker in miR-195 mimics group than NC group (p0.001). Furthermore, it was also significantly weaker in si-TLR4 + miR-195 inhibitor group than si-TLR4 group (p0.05).MiR-195 reduces the release of inflammatory factors and inhibits the proliferation of macrophages through targeting TLR4 and blocking the NF-κB pathway, thereby alleviating the symptoms of DN rats.

The formation of iron-sulfur-arsenic (Fe–S–As) minerals during biogeochemical processes in As contaminated aquifers remains poorly understood despite their importance to understanding As release and transport in such systems. In this study, X-ray absorption and Mossbauer spectroscopies complemented by electron microscopy, and chemical extractions were used to examine vertical changes of As, Fe and S speciation for the example of sediments in the Hetao Basin. Reduction of Fe(III), As(V) and SO42- species were shown to co-occur in the aquifers. Iron oxides were observed to be predominantly goethite and hematite (36 – 12%) and appeared to decrease in abundance with depth. Furthermore, reduced As (including arsenite and As sulfides) and sulfur species (including S(-II), S(-I) and S0) increased from 16% to 76% and from 13% to 44%, respectively. Iron oxides were the major As carrier in the sediments, and the lower groundwater As concentration consists with less desorbable and reducible As in the sediments. The formation of As-Fe sulfides (e.g., As containing pyrite and greigite) induced by redox heterogeneities likely contribute to localized lower groundwater As concentrations. These results help to further elucidate the complex relationship between biogeochemical processes and minerals formation in As contaminated aquifers.

To design and evaluate a novel oxyntomodulin (OXM) derivative with albumin-binding helix domain and dual GLP-1 receptor (GLP-1R) and glucagon receptor (GcgR) activation activity to achieve metabolize improvement on the diabetes-related complication.Mutation (D-Ser2) on OXM was performed and then different helix albumin-binding domains were fused to the mutated OXM via a thrombin-cleavable linker to generate seven fusion peptides, named LM01-LM07. Seven LM peptides were synthesized and screened via in vitro receptor activation test, albumin binding measurement and protease cleavage assay to select potent candidate peptide for further in vivo study. Moreover, acute and chronic efficacy studies were conducted to evaluate the efficacy of selected candidate using db/db mice.LM06, as selected OXM derivative, exhibited higher albumin-binding affinity, sustained-release efficiency and balanced activation activities on both GLP-1R and GcgR compared with other ones. Moreover, LM06 was demonstrated with improved hypoglycemic and insulinotropic abilities in receptor-deficient mice via activating GLP-1R. In addition, prolonged anti-diabetic efficacies of LM06 were demonstrated via hypoglycemic duration assay and OGTT in db/db mice. Further pharmacokinetic test of LM06 in both rats and monkeys identified improved half-life and other metabolic characteristics. Nevertheless, 8-week subcutaneously dosed LM06 in db/db mice achieved prominent efficacies on glucostasis, weight-lowering, pancreatic function and adipogenesis via activating GLP-1R and GcgR. Moreover, LM06 also could accelerate diabetic skin wound closure in combination with low-intensity ultrasound.LM06, as a long-acting dual GLP-1R/GcgR agonist, exerts potential as a once-weekly therapeutic candidate against diabetes-related complication in combination with low-intensity ultrasound.