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The Rho kinase inhibitor fasudil exerts neuroprotective effects. We previously showed that fasudil can regulate M1/M2 microglia polarization and inhibit neuroinflammation. Here, the therapeutic effect of fasudil on cerebral ischemia‑reperfusion (I/R) injury was investigated using the middle cerebral artery occlusion and reperfusion (MCAO/R) model in Sprague‑Dawley rats. The effect of fasudil on the phenotype of microglia and neurotrophic factors in the I/R brain and its potential molecular mechanism was also explored. It was found that fasudil ameliorated neurological deficits, neuronal apoptosis, and inflammatory response in rats with cerebral I/R injury. Fasudil also promoted the polarization of microglia into the M2 phenotype, in turn promoting the secretion of neurotrophic factors. Furthermore, fasudil significantly inhibited the expression of TLR4 and NF‑κB. These findings suggest that fasudil could inhibit the neuroinflammatory response and reduce brain injury after I/R injury by regulating the shift of microglia from an inflammatory M1 phenotype to an anti‑inflammatory M2 phenotype, which may be related to the regulation of the TLR4/ NF‑κB signal pathway.

Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), are characterized by the progressive degeneration of neurons. Although the etiology and pathogenesis of neurodegenerative diseases have been studied intensively, the mechanism is still in its infancy. In general, most neurodegenerative diseases share common molecular mechanisms, and multiple risks interact and promote the pathologic process of neurogenerative diseases. At present, most of the approved drugs only alleviate the clinical symptoms but fail to cure neurodegenerative diseases. Numerous studies indicate that dietary plant polyphenols are safe and exhibit potent neuroprotective effects in various neurodegenerative diseases. However, low bioavailability is the biggest obstacle for polyphenol that largely limits its adoption from evidence into clinical practice. In this review, we summarized the widely recognized mechanisms associated with neurodegenerative diseases, such as misfolded proteins, mitochondrial dysfunction, oxidative damage, and neuroinflammatory responses. In addition, we summarized the research advances about the neuroprotective effect of the most widely reported dietary plant polyphenols. Moreover, we discussed the current clinical study and application of polyphenols and the factors that result in low bioavailability, such as poor stability and low permeability across the blood-brain barrier (BBB). In the future, the improvement of absorption and stability, modification of structure and formulation, and the combination therapy will provide more opportunities from the laboratory into the clinic for polyphenols. Lastly, we hope that the present review will encourage further researches on natural dietary polyphenols in the treatment of neurodegenerative diseases.

Activation of the NLRP3 inflammasome and its mediated neuroinflammation are implicated in neurodegenerative diseases, while mitophagy negatively regulates NLRP3 inflammasome activation. SHP-2, a protein-tyrosine phosphatase, is critical for NLRP3 inflammasome regulation and inflammatory responses. In this study, we investigated whether triterpenoid saponins in Radix Polygalae inhibit the NLRP3 inflammasome via mitophagy induction. First, we isolated the active fraction (polygala saponins (PSS)) and identified 17 saponins by ultra-performance liquid chromatography coupled with diode-array detection and tandem quadrupole time-of-flight mass spectrometry (UHPLC-DAD-Q/TOF-MS). In microglial BV-2 cells, PSS induced mitophagy as evidenced by increased co-localization of LC3 and mitochondria, as well as an increased number of autophagic vacuoles surrounding the mitochondria. Furthermore, the mechanistic study found that PSS activated the AMPK/mTOR and PINK1/parkin signaling pathways via the upregulation of SHP-2. In Aβ(1-42)-, A53T-α-synuclein-, or Q74-induced BV-2 cells, PSS significantly inhibited NLRP3 inflammasome activation, which was attenuated by bafilomycin A1 (an autophagy inhibitor) and SHP099 (an SHP-2 inhibitor). In addition, the co-localization of LC3 and ASC revealed that PSS promoted the autophagic degradation of the NLRP3 inflammasome. Moreover, PSS decreased apoptosis in conditioned medium-induced PC-12 cells. In APP/PS1 mice, PSS improved cognitive function, ameliorated Aβ pathology, and inhibited neuronal death. Collectively, the present study, for the first time, shows that PSS inhibit the NLRP3 inflammasome via SHP-2-mediated mitophagy in vitro and in vivo, which strongly suggests the therapeutic potential of PSS in various neurodegenerative diseases.

Major depressive disorder is characterized by the deficiencies of monoamine neurotransmitters, neurotrophic factors and persistent neuroinflammation. Microglial activation has been associated with neuroinflammation-related mental diseases, accompanied by NLR family pyrin domain containing 3 (NLRP3) inflammasome. Here, we investigated the effect of NLRP3 inhibition by its small molecular inhibitor MCC950 on inflammatory activity and depressive-like mice induced by chronic unpredictable mild stress (CUMS), followed by the behavioral tests including sucrose preference test and forced swimming test. NLRP3/caspase-1/IL-1β signaling and microglial morphology in the prefrontal cortex were measured. The results showed that CUMS caused a decrease in sucrose preference and an increase in immobility time, which were reversed by NLRP3 inhibitor MCC950. In addition, NLRP3 inhibition decreased the number of microglia and changed the activated state of microglia to a resting state by morphology 3D reconstruction. Moreover, NLRP3 inhibition inactivated NLRP3/caspase-1/IL-1β signaling in the prefrontal cortex. The results from immunofluorescence demonstrated that NLRP3 and IL-1β expression was decreased in microglia in response to MCC950 treatment. Accordingly, proinflammatory cytokines were also decreased by NLRP3 inhibition. In conclusion, this study demonstrates that microglial NLRP3 inhibition prevents stress-induced neuroinflammation in the prefrontal cortex and suggests that microglial NLRP3 could be one of the potential therapeutic targets for depression treatment.

To observe the effect of acupuncture on microglia polarization and inflammatory reaction in rats with cerebral ischemia-reperfusion injury (CIRI), so as to explore its mechanisms underlying improvement of CIRI.Thirty male SD rats were randomly divided into sham operation, model, and acupuncture groups, with 10 rats in each group. The CIRI model was established by occlusion of the middle cerebral artery (MCAO) for 1 h, followed by reperfusion. After modeling, rats in the acupuncture group received manual acupuncture stimulation of "Dazhui" (GV14), "Baihui"(GV20), "Shuigou" (GV26), bilateral "Zusanli" (ST36) and "Fengchi" (GB20) by twirling the needles rapidly for 10 s/acupoint every 10 min, with the needles retained for 20 min. The treatment was conducted once daily for successive 7 days. The neurological function was evaluated according to Longa's method. The state of CIRI was observed after Nissl staining, and the expression levels of Iba-1, iNOS, Arg1, BDNF, GDNF and NeuN in the ischemic cortex tissue were detected by immunofluorescence staining. The contents of TNF-α, IL-6 and IL-10 in the ischemic tissue were assayed by ELISA. The protein expression levels of BDNF, GDNF, TLR4, MyD88 and NF-κB in the ischemic tissues were detected by Western blot.The neurological deficit score on the 24 h and 7th day was considerably higher in the model group than in the sham operation group (Acupuncture intervention can improve neurological function in CIRI rats, which may be related to its effects in regulating the polarization of microglia, reducing inflammatory reaction and increasing the secretion of neurotrophic factors in the brain, inhibiting TLR4/MyD88/NF-κB signaling pathway.

Lagotis brachystachya Maxim, a common herb in Tibetan medicine, is mainly used to treat pneumonia, hepatitis, yellow water disease (gouty arthritis). Since long-term heavy drinking is also a risk factor for gouty arthritis, the present study aimed to evaluate the underlying protective role and mechanism of extracts of Lagotis brachystachya (ELB) in chronic alcoholic liver injury combined with gouty arthritis. The rat chronic alcoholic liver injury combined with gouty arthritis model was established by long-term alcohol consumption and monosodium urate (MSU) injection. The therapeutical action of ELB was then evaluated by biochemical measurement, histopathological examination, ankle swelling assessment, and protein detection. According to biochemical measurements and histopathological evaluation, ELB could alleviate the symptoms of alcoholic liver injury combined with gouty arthritis. In addition, chronic alcohol consumption and MSU activated inflammatory-related signaling such as TLR4/MyD88/NF-κB, NLRP3, and JAK2/STAT3 pathways in the liver and synovial tissues, while ELB significantly inhibited the activation of the inflammatory signaling pathway. In conclusion, ELB is protective in rats with chronic alcoholic liver injury and gouty arthritis, possibly mediated by the inhibition of TLR4/MyD88/NF-κB, NLRP3, and JAK2-STAT3 signaling pathways in both the hepatic and synovial tissues.

In view of the frequent occurrence of floods due to climate change, and the fact that a large calculation domain, with complex land types, is required for solving the problem of the flood simulations, this paper proposes an optimized non-uniform grid model combined with a high-resolution model based on the graphics processing unit (GPU) acceleration to simulate the surface water flow process. For the grid division, the topographic gradient change is taken as the control variable and different optimization criteria are designed according to different land types. In the numerical model, the Godunov-type method is adopted for the spatial discretization, the TVD-MUSUL and Runge-Kutta methods are used to improve the model’s spatial and temporal calculation accuracies, and the simulation time is reduced by leveraging the GPU acceleration. The model is applied to ideal and actual case studies. The results show that the numerical model based on a non-uniform grid enjoys a good stability. In the simulation of the urban inundation, approximately 40%–50% of the urban average topographic gradient change to be covered is taken as the threshold for the non-uniform grid division, and the calculation efficiency and accuracy can be optimized. In this case, the calculation efficiency of the non-uniform grid based on the optimized parameters is 2–3 times of that of the uniform grid, and the approach can be adopted for the actual flood simulation in large-scale areas.

The B6Ca2 and B8Ca2 clusters adopt interesting inverse sandwich architectures, featuring a prolate B6 (or perfect B8) ring jammed with two capping Ca atoms. Both clusters show the high thermodynamic stability due to the double (σ and π) electronic delocalization. In present paper, we computationally studied the hydrogen storage of them. The results suggest that each Ca site in B6Ca2 and B8Ca2 clusters could store up six H2, yielding a gravimetric density of 14.2 wt% for B6Ca2 and 12.6 wt% for B8Ca2. The average adsorption energy for H2-adsorbed B6Ca2 and B8Ca2 complexes is within the scope of 0.12–0.15 eV per H2 at wB97XD level, hinting that two clusters could reversibly store and release hydrogen, which is positively confirmed by the Born-Oppenheimer molecular dynamics simulations. Both B6Ca2 and B8Ca2 nanoclusters are feasible hydrogen storage media under the ambient condition.

The preparation of MgO nanoparticles with relatively small sizes and highly active surface areas is still a great challenge nowadays. The principal objective of this work was to investigate and optimize the calcined conditions of MgO with smaller sizes and higher surface areas, which contributed to its better degradation ability towards paraoxon pollutants. Firstly, the aerogel Mg(OH)2 nanosheets with an increased surface area of 349.0 m2/g was prepared via a combined sol–gel-hydrothermal method. Then the calcined MgO nanoparticles with different morphology, size dimensions, and specific surface areas were obtained at different calcination temperatures from 400 to 800 °C. The optimized average grain size of MgO obtained at 600 °C was achieved to 8.7 ± 3.2 nm with a relatively high surface area up to 231.4 m2/g. Meanwhile, such as-prepared MgO nanoparticles showed an excellent performance towards paraoxon degradation, and the maximum degradation amount of paraoxon-ethyl was up to 57.8 mg/g@90 min at room temperature. The kinetics of degradation was consistent with the pseudo-second-order model (R2 > 0.99). Such excellent degradation capacity was derived from more generations of superoxide radical (•O2−) sites as revealed by using the nitro blue tetrazolium (NBT) as a probe. The results indicated that the MgO nanoparticles reported herein could be an effective candidate for the environmental remediation of organophosphorus toxin pollutants due to their facile scale-up, low cost, eco-friendly characteristic, and high removal efficiency.

In Chinese society, the teachers' professional ethics have been considered important since ancient times and have been widely discussed. This paper aims to explore the mechanism of the influence of differential leadership with local cultural adaptability on college teachers' professional ethics. A total of 403 valid responses were collected from a questionnaire survey of university teachers in many regions of China, and the data were statistically analysed by SPSS17.0 and AMOS22.0. The results showed that differential leadership positively influences college teachers' professional ethics, and college teachers' professional identity plays a mediating role between differential leadership and teachers' professional ethics. The effect of differential leadership on college teachers' professional identity and professional ethics is negatively moderated by the tendency towards collectivism, and it seems to be contrary to the national culture of Chinese, which is high in collectivism, but consistent with the strong will of college teachers and the current workplace characteristics embodied in the sample investigated. It is expected that the research results of this paper can provide theoretical guidance for the construction of teachers' professional ethics in relevant governments and colleges.

Peroxynitrite (ONOO−) is a reactive oxygen species (ROS) that causes serious damage to living cells and is the cause of a series of human diseases. It is reported that mitochondria are the major site of ONOO− production. Therefore, accurate and rapid detection of intracellular ONOO− is important in pathological processes. Herein, a mitochondria-targeted ratiometric fluorescent probe (DMANI) has been rationally designed based on the coumarin–hemicyanine hybrid framework by regulating the intramolecular charge transfer (ICT) effect. The DMANI can capture ONOO− at low concentrations via direct addition with the CC bond to give an obvious fluorescent signal change from red to blue based on the ICT process. The possible mechanism for this electrophilic addition process was confirmed using electrospray ionization mass spectrometry (ESI-MS) and 1H-NMR spectra. DMANI exhibited a good selectivity, a large Stokes shift (248 nm), a low detection limit (40 nM), and a rapid response (within 20 s) to ONOO−. More importantly, DMANI was successfully used for ratiometric imaging and monitoring of the fluctuations of mitochondrial ONOO− in living cells.

The photoelectrocatalytic performance of (Sb,N)-MnO2 are explored by experiment and first principle calculation based on density functional theory. The photoelectrochemical performance test shows that 6% (Sb,N)-MnO2 with maximum electrochemical active area and minimum charge transfer resistance has a oxygen evolution potential of 1.59 V. At this ratio, the photocurrent density reaches 8.00 mA·cm-2 and the the degradation rate is 87.89%. Furthermore, the possible role of Sb and N doping in modifying the photoelectrocatalytic performance is studied theoretically. The band gap decreases from 0.944 eV to 0.203 eV due to the formation of charge compensation effect, which is conducive to the photoelectrocatalytic performance. The theoretical predictions agree well with the experimental results, which can provide an ideal alternative material for wastewater treatment.

Background Major depressive disorder is characterized by not only monoamine neurotransmitters deficiencies but also persistent neuroinflammation. The complement system is an attractive therapeutic target for various inflammation-related diseases due to its early activation in inflammatory processes. Results In the present study, the dynamic alteration of complement C3 and its receptor C3aR during the occurrence of depression and the mechanism of astrocyte-microglia IL-1R/C3/C3aR on synaptic pruning were investigated. The proteomic analysis firstly showed that chronic stress caused an elevation of C3. GO analysis indicated that complement system-mediated synaptic pruning signaling was involved in depression. The dynamic observation indicated that C3/C3aR was activated in the early onset and throughout the course of depression induced by lipopolysaccharide (LPS) and chronic stress. In contrast, C3aR blockade inhibited the hyperactivation of microglial APT2/DHHC7 palmitoylation cycle, which mediated the translocation of STAT3 and the expression of proinflammatory cytokines. Meanwhile, C3aR blockade also attenuated the synaptic pruning and enhanced the synaptogenesis in the prefrontal cortex of mice. Moreover, the blockade of IL-1R/NF-κB signaling pathway reduced the release of C3 from astrocyte. Conclusions The current study demonstrates that astrocyte-microglia IL-1R/C3/C3aR activation causes the abnormal synaptic pruning in depression, and suggests that the activation of complement C3/C3aR may be particularly helpful in predicting the onset stage of depression.

Pontine warning syndrome (PWS) occurs rarely and is characterized by recurrent, stereotyped episodes of motor or sensory dysfunction, dysarthria, or ophthalmoplegia leading to pontine infarction. Restless legs syndrome (RLS) is a distinct neurological sensorimotor disorder. Pontine infarction is a rare but possible cause of RLS. Here, we report the case of a 58-year-old woman who experienced unilateral RLS in concomitance with stereotyped episodes of left-sided weakness and dysarthria, and developed an acute paramedian pontine infarction eventually. To the best of our knowledge, no other cases of PWS coinciding with RLS in the progression of pontine infarction have been reported in the literature. Furthermore, we discussed the potential mechanisms of PWS and RLS secondary to pontine infarction, which may be helpful for managing such patients.

The typical electron-deficiency of the boron element renders fascinating architectures and chemical bonding to boron-based nanoclusters. We theoretically predict two di-Ca-doped boron clusters, B6Ca2 (D2h, 1Ag) and B8Ca2 (D8h, 1A1g), and both adopt interesting inverse sandwich geometries, showing an elongated D2h B6 or perfectly planar D8h B8 ring being sandwiched by two Ca atoms only, respectively. Natural atomic charge analyses indicate that the Ca atoms donate nearly all the 4s electrons to the B6 (or B8) ring, forming [Ca]2+[B6]4−[Ca]2+ and [Ca]2+[B8]4−[Ca]2+ charge transfer complexes. The interaction between the two Ca atoms and the boron rings is governed by robust electrostatics albeit by weaker B–Ca covalent interaction. Chemical bonding analyses show that B6Ca2 has 4σ and 6π delocalized electrons on the elongated B6 ring, leading to a conflicting aromatic system. B8Ca2, possessing 6σ and 6π delocalized electrons on the B8 ring, is doubly aromatic. Additionally, the B6Ca2 and B8Ca2 clusters show noticeable structural and electronic transmutation relative to their equivalent electronic B6Be2 and B8Mg2 clusters, respectively. The intrinsic reasons behind the transmutations are elucidated via in-depth bonding analyses.

Nutrition intervention has emerged as a potential strategy to delay aging and promote healthy longevity. Citri Reticulatae Semen (CRS) has diverse beneficial effects and has been used for thousands of years to treat pain. However, the health benefits of CRS in prolonging health span and improving aging-related diseases and the exact mechanisms remain poorly characterized. In this study, Caenorhabditis elegans (C. elegans) was used as a model organism to study the antiaging and health span promoting activities of 75% ethanol extract of CRS (CRSE). The results showed that treatment with CRSE at 1 000 μg/mL significantly extended the life span of worms by 18.93% without detriment to health span and fitness, as evidenced by the delayed aging-related phenotypes and increased body length and width, and reproductive output. In addition, CRSE treatment enhanced the ability of resistance to heat, oxidative, and pathogenic bacterial stress. Consistently, heat shock proteins and antioxidant enzyme-related and pathogenesis-related genes were up-regulated by CRSE treatment. Furthermore, CRSE supplementation also improved α-synuclein, 6-OHDA, and polyQ40-induced pathologies in transgenic C. elegans models of Parkinson’s disease and Huntington’s disease. The mechanistic study demonstrated that CRSE induced autophagy in worms, while the RNAi knockdown of 4 key autophagy-related genes, including lgg-1, bec-1, vps-34, and unc-51, remarkably abrogated the beneficial effects of CRSE on the extending of life span and health span and neuroprotection, demonstrating that CRSE exerts beneficial effects via autophagy induction in worms. Together, our current findings provide new insights into the practical application of CRS for the prevention of aging and aging-related diseases.

Lagotis brachystachya Maxim is a characteristic herb commonly used in Tibetan medicine. Tibetan medicine records it as an important medicine for the clinical treatment of “Yellow Water Disease,” the symptoms of which are similar to that of arthritis. Our previous study showed that the flavonoid fraction extracted from L. brachystachya could attenuate hyperuricemia. However, the effects of the active flavonoids on gouty arthritis remain elusive, and the underlying mechanism is not understood. In the present study, the effects of the active flavonoids were evaluated in rats or Raw264.7 cells with gouty arthritis induced by monosodium urate (MSU) crystal, followed by the detection of TLR4, MyD88, pNF-κB, and NLR family pyrin domain-containing 3 (NLRP3) expression. The swelling of the ankle joint induced by MSU crystal began to be relieved 6 h post the administration with the active flavonoids. In addition, the active flavonoids not only alleviated MSU crystal-induced inflammation in synovial tissues by histopathological examination but also reduced tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) levels in the joint tissue fluid of MSU crystal-induced rats. Furthermore, Western blot analysis indicated that the active flavonoids reduced the production of these cytokines by inhibiting the TLR4/MyD88/NF-κB pathway and decreasing NLRP3 expression in synovial tissues of rats. More importantly, the inhibition of TLR4/MyD88/NF-κB pathway and NLRP3 expression was also confirmed in MSU-induced Raw264.7 cells. In conclusion, these results indicated that the active flavonoids from L. brachystachya could effectively attenuate gouty arthritis induced by MSU crystal through the TLR4/MyD88/NF-κB pathway and NLRP3 expression in vivo and in vitro, suggesting several potential candidates for the treatment of gouty arthritis.

We have previously shown that biochanin A exhibits neuroprotective properties in the context of cerebral ischemia/reperfusion (I/R) injury. The mechanistic basis for such properties, however, remains poorly understood. This study was therefore designed to explore the manner whereby biochanin A controls endoplasmic reticulum (ER) stress, apoptosis, and inflammation within fetal rat primary cortical neurons in response to oxygen-glucose deprivation/reoxygenation (OGD/R) injury, and in a rat model of middle cerebral artery occlusion and reperfusion (MCAO/R) injury. For the OGD/R in vitro model system, cells were evaluated after a 2 h OGD following a 24 h reoxygenation period, whereas in vivo neurological deficits were evaluated following 2 h of ischemia and 24 h of reperfusion. The expression of proteins associated with apoptosis, ER stress (ERS), and p38 MAPK phosphorylation was evaluated in these samples. Rats treated with biochanin A exhibited reduced neurological deficits relative to control rats following MCAO/R injury. Additionally, GRP78 and CHOP levels rose following I/R modeling both in vitro and in vivo, whereas biochanin A treatment was associated with reductions in CHOP levels but further increases in GRP78 levels. In addition, OGD/R or MCAO/R were associated with markedly enhanced p38 MAPK phosphorylation that was alleviated by biochanin A treatment. Similarly, OGD/R or MCAO/R injury resulted in increases in caspase-3, caspase-12, and Bax levels as well as decreases in Bcl-2 levels, whereas biochanin A treatment was sufficient to reverse these phenotypes. Together, these findings thus demonstrate that biochanin A can alleviate cerebral I/R-induced damage at least in part via suppressing apoptosis, ER stress, and p38 MAPK signaling, thereby serving as a potent neuroprotective agent.

Background: The COVID-19 pandemic has been an emergency worldwide. Web-based physical education is a choice for college students to keep on their study. The aim of this study was to compare the data of physical fitness of college students before and after web-based physical education.Methods: All the students of 2018 and 2019 in Wuhan University of Technology who had taken the web-based physical education class in 2020 were included in this study. The records of annual physical fitness tests of all the subjects in 2019 and 2020 which were carried out in September were reviewed, including weight, height, body mass index (BMI), vital capacity (VC), 50-m dash, sit-and-reach, standing long jump, male-specific pull-ups and 1,000-m race, and female-specific sit-ups and 800-m race.Results: There were 24,112 male and 9,690 female records of physical fitness tests included in our study. The results of 11,219 male and 4,651 female students who completed both physical fitness tests in 2019 and 2020 were employed for Wilcoxon signed-rank test. Declined performance was observed on male 50-m dash by 0.1 s, male 1,000-m race by 14 s, and female 800-m race by 11 s. Notably, the percentage of male obesity, based on BMI, rose from 10.6 to 15.2% and 17.1 to 21.8% for male overweight; correspondingly, the percentage of male normal weight declined from 55.9 to 51.9% and 16.4 to 11.1% for male thinness. The trend of increasing BMI in males should be paid attention to. Improved results on vital capacity, sit-and-reach, standing long jump for both males and females, female 50-m dash, female sit-ups, and male pull-ups were observed in 2020. All the results of physical fitness tests were significantly different between 2019 and 2020 (p < 0.01) by Wilcoxon signed-rank test.Conclusions: The changes of physical fitness tests before and after web-based physical education suggested that the focus should be placed on improvement for running tests through appropriate alternatives, such as fast running in place and shuttle run. In addition, the simple, convenient, and practical sport that require available equipment and little field should be considered for web-based physical education.

Gynostemma pentaphyllum is a herbal medicine widely used in Asian countries, and its saponin extracts have been shown to possess potent anti-inflammatory effects. Gypenoside XVII, an active ingredient isolated from Gynostemma pentaphyllum, has been found to alleviate the inflammation induced by LPS in the BV2 microglia, according to our preliminary study. This study aims to evaluate whether Gypenoside XVII could attenuate depression-like symptoms in vivo and tries to demonstrate the involvement of the complement regulation in its antidepressant-like effect. The results showed that Gypenoside XVII significantly attenuated depression-like behaviors in the forced swimming test, tail suspension test and sucrose preference test. It also alleviated the acute stress-induced hyperactivity of serum corticosterone levels. Additionally, Gypenoside XVII significantly inhibited the activation of microglia and the expression of C3 in mice exposed to chronic unpredictable mild stress (CUMS). Meanwhile, the activation of C3aR/STAT3 signaling and the expression of proinflammatory cytokines was reversed by Gypenoside XVII. Moreover, CUMS induced excessive synaptic pruning by activating microglia, while Gypenoside XVII restored it in the prefrontal cortex. Our data demonstrated that Gypenoside XVII, the active ingredient of Gynostemma pentaphyllum, produced the antidepressant-like effects in mice, which was mediated by the inhibition of complement C3/C3aR/STAT3/cytokine signaling in the prefrontal cortex.

Genetic variation is the driving force of plant-pathogen co-evolution. Large-scale genetic variations such as structural variations (SVs) often alter genome stability and organismal fitness. However, the pangenomic landscape and functional implications of SVs remain largely unexplored in plant pathogens. Here, we characterized the pangenomic and SV landscape in wheat head blight fungus Fusarium graminearum by producing and comparing chromosome-level (average contig N50 of 8.9 Mb) genome assemblies of 98 accessions using a reference-guided approach. Accounting for 29.05% and 19.01% of F. graminearum pangenome, respectively, accessory and private genomes are enriched with functions related to membrane trafficking, metabolism of fatty acids and tryptophans, with the private also enriched with putative effectors. Furthermore, using chromosome-level assemblies, we detected 52,420 SVs, 69.51% of which are inaccessible using read-mapping based approach. Over a half (55.65%) of 52,645 merged SVs affected 1,660 protein-coding genes, the most variable of which are involved in fungal virulence, cellular contact and communications. Interestingly, highly variable effectors and secondary metabolic enzymes are co-localized with SVs at subtelomeric and centromeric regions. Collectively, this landmark study shows the prevalence and functional relevance of SVs in F. graminearum, providing a valuable resource for future pangenomic studies in this cosmopolitan pathogen of cereal crops.

Brain imaging-derived phenotypes (IDPs) serve as underlying functional intermediates in psychiatric disorders, both of which are highly polygenic and heritable. Observational studies have elucidated the correlation between IDPs and psychiatric disorders, yet no systematic screening of IDPs to confer the causal liability in such disorders. We conducted a bidirectional two-sample Mendelian randomization framework to explore the causality of 1,901 IDPs on 10 psychiatric disorders and established the BrainMR database (http://brainmr.online/idp2psy/Index.php). We identified 17 causalities in forward MR analyses and 14 causalities in reverse MR analyses, which all rigorously examined them through various sensitivity analyses. The top significant relationship in forward was a unit lower volume of right central lateral of the thalamic nuclei, which was causally associated with an increased anorexia nervosa risk with an estimated OR of 0.52 (95% CI 0.41-0.64, P = 3.32 × 10−9). In reverse, the top significant IDP to be affected was the area of superior segment of the circular sulcus of the insula in the right hemisphere, which was increased by the reason of SCZ risk with an estimated association effect size of 0.068 (95% CI 0.046-0.090, P = 1.12 × 10−6). Overall, our study provides unique insights into causal pathways of psychiatric disorders at the imaging levels.

Cationic therapeutic peptides have received widespread attention due to their excellent antibacterial and antitumor properties. However, most of these peptides have undesirable delivery efficiency and high hemolytic toxicity due to the positively charged α-helix structure containing many lysine and arginine, which may restrict its in vivo applications. Herein, a conformationally transformed therapeutic peptide Pep-HCO3 modified with bicarbonates on guanidine groups is designed. Such a design allows Pep-HCO3 ((nap-RAGLQFPVGRLLRRLLRRLLR) nHCO3 ) to self-assemble into nanoparticles (NP-Pep) due to disrupting helix folding and the formation of intermolecular hydrogen bonding between bicarbonates and guanidine groups. When pH is from 7.4 to 6.5 at the tumor sites, guanidine bicarbonate can be hydrolyzed to form CO2 and guanidine groups, resulting in the disassembling of the NP-Pep into monomers α-Pep with a positively charged α-helix structure. In vivo, NP-Pep not only inhibits the tumor growth of xenografted mice with a twofold enhanced inhibition rate compared with α-Pep treatment group, but also significantly reduces the hemolytic toxicity by responding to the pH of tumor microenvironment. Therefore, the strategy of conformational transition-triggered disassembly of nanoparticles allows efficient delivery of cationic therapeutic peptides and lowering the hemolytic toxicity, which may provide an avenue for developing high-performance cationic peptide in vivo applications.

The application of artificial intelligence in the field of primary health care can effectively improve diagnosis and treatment,avoid over-examination and over-medication,and make up for the shortage of high-quality medical resources in primary medical and health institutions.Focusing on the application of artificial intelligence in the field of primary health care,this paper analyzes the existing application modes and typical cases,studies its main stakeholders,interest demands and problems,and provides corresponding suggestions.

We have previously shown that biochanin A exhibits neuroprotective properties in the context of cerebral ischemia/reperfusion (I/R) injury. The mechanistic basis for such properties, however, remains poorly understood. This study was therefore designed to explore the manner whereby biochanin A controls endoplasmic reticulum (ER) stress, apoptosis, and inflammation within fetal rat primary cortical neurons in response to oxygen-glucose deprivation/reoxygenation (OGD/R) injury, and in a rat model of middle cerebral artery occlusion and reperfusion (MCAO/R) injury. For the OGD/R in vitro model system, cells were evaluated after a 2 h OGD following a 24 h reoxygenation period, whereas in vivo neurological deficits were evaluated following 2 h of ischemia and 24 h of reperfusion. The expression of proteins associated with apoptosis, ER stress (ERS), and p38 MAPK phosphorylation was evaluated in these samples. Rats treated with biochanin A exhibited reduced neurological deficits relative to control rats following MCAO/R injury. Additionally, GRP78 and CHOP levels rose following I/R modeling both in vitro and in vivo, whereas biochanin A treatment was associated with reductions in CHOP levels but further increases in GRP78 levels. In addition, OGD/R or MCAO/R were associated with markedly enhanced p38 MAPK phosphorylation that was alleviated by biochanin A treatment. Similarly, OGD/R or MCAO/R injury resulted in increases in caspase-3, caspase-12, and Bax levels as well as decreases in Bcl-2 levels, whereas biochanin A treatment was sufficient to reverse these phenotypes. Together, these findings thus demonstrate that biochanin A can alleviate cerebral I/R-induced damage at least in part via suppressing apoptosis, ER stress, and p38 MAPK signaling, thereby serving as a potent neuroprotective agent.

The typical electron-deficiency of the boron element renders fascinating architectures and chemical bonding to boron-based nanoclusters. We theoretically predict two di-Ca-doped boron clusters, B6Ca2 (D2h, 1Ag) and B8Ca2 (D8h, 1A1g), and both adopt interesting inverse sandwich geometries, showing an elongated D2h B6 or perfectly planar D8h B8 ring being sandwiched by two Ca atoms only, respectively. Natural atomic charge analyses indicate that the Ca atoms donate nearly all the 4s electrons to the B6 (or B8) ring, forming [Ca]2+[B6]4-[Ca]2+ and [Ca]2+[B8]4-[Ca]2+ charge transfer complexes. The interaction between the two Ca atoms and the boron rings is governed by robust electrostatics albeit by weaker B-Ca covalent interaction. Chemical bonding analyses show that B6Ca2 has 4σ and 6π delocalized electrons on the elongated B6 ring, leading to a conflicting aromatic system. B8Ca2, possessing 6σ and 6π delocalized electrons on the B8 ring, is doubly aromatic. Additionally, the B6Ca2 and B8Ca2 clusters show noticeable structural and electronic transmutation relative to their equivalent electronic B6Be2 and B8Mg2 clusters, respectively. The intrinsic reasons behind the transmutations are elucidated via in-depth bonding analyses.

Background: This study aimed to develop a predictive model based on the risk of locoregional recurrence (LRR) in epidermal growth factor receptor (EGFR)-mutant stage III-pN2 lung adenocarcinoma after complete resection. Methods: A total of 11,020 patients with lung surgery were screened to determine completely resected EGFR-mutant stage III-pN2 lung adenocarcinoma. Patients were excluded if they received preoperative therapy or postoperative radiation therapy (PORT). The time from surgery to LRR was recorded. Clinicopathological variables with statistical significance predicting LRR in the multivariate Cox regression were incorporated into the competing risk nomogram. Patients were then sub-grouped based on different recurrence risk as a result of the nomogram. Results: Two hundred and eighty-eight patients were enrolled, including 191 (66.3%) with unforeseen N2 (IIIA1-2), 75 (26.0%) with minimal/single station N2 (IIIA3), and 22 (7.6%) with bulky and/or multilevel N2 (IIIA4). The 2-year overall cumulative incidence of LRR was 27.2% (confidence interval [CI], 16.3%-38.0%). IIIA4 disease (hazard ratio, 2.65; CI, 1.15-6.07; P=0.022) and extranodal extension (hazard ratio, 3.33; CI, 1.76-6.30; P

To evaluate the clinical efficacy of single administration of Tripterygium Glycosides Tablets(TGT) or combined administration with methotrexate(MTX) against rheumatoid arthritis(RA) based on American College of Rheumatology(ACR) efficacy standard. Six databases, namely CNKI, WanFang, VIP, PubMed, Embase and Cochrane Library, were retrieved for randomized controlled trials(RCT), and clinical trials were screened out according to the preset inclusion and exclusion criteria. Then, the study quality was evaluated by the risk assessment tools. Data extraction and analysis were performed by using RevMan 5.3 software for Meta-analysis. Sensitivity analysis and publication bias analysis were made to test the stability and reliability of results. Until December 2018, a total of 1 709 articles were obtained, and finally 10 clinical RCT studies with a total of 1 184 patients were included. As a result, the single administration of TGT showed a significantly better ACR efficiency(RR=1.31, 95%CI[1.15, 1.49], Plt;0.000 1) than methotrexate(MTX). The combined administration of TGT and MTX showed a significantly better ACR efficiency(RR=1.28, 95%CI[1.20, 1.38], Plt;0.000 01) than the single administration of MTX. In conclusion, the single administration of TGT and the combined administration of TGT and MTX were more effective in achieving ACR20, ACR50, ACR70 compliance than the single administration of MTX. Further validations based on more RCT studies with high-quality are required.

To systematically evaluate the effects of Tripterygium Glycosides Tablets alone or in combination with methotrexate(MTX) and leflunomide(LEF) on the levels of pro-inflammatory cytokines in patients or animal models with rheumatoid arthritis(RA), and to provide reference for clinical application and related basic research, this study systematically searched databases of CNKI, VIP, WanFang, PubMed, Embase and Cochrane Library, collected relevant clinical or animal experimental studies, used risk assessment tools to evaluate the quality of research, and used Revman 5.3 software to conduct Meta-analysis or descriptive analysis of the outcome indicators included in the literatures. Of the 1 709 papers retrieved, 3 clinical studies and 12 animal experiments were included. The results showed that compared with MTX alone, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of peripheral blood TNF-α(SMD=-8.88,95%CI[-10.77,-6.99],Plt;0.000 01),IL-1β(Plt;0.000 01) and IL-6(SMD=-8.63, 95%CI[-10.57,-6.69], Plt;0.000 01) in RA patients. Compared with LEF alone, the combination of Tripterygium Glycosides Tablets and LEF could not further reduce the expression levels of TNF-α(P=0.20), IL-1β(P=0.17), IL-6(P=0.31). In RA animal model, compared with model group, Tripterygium Glycosides Tablets could reduce the expression levels of peripheral blood IL-1β(SMD=-6.29,95%CI[-9.64,-2.93],Plt;0.000 2)in peripheral blood(SMD=-1.39,95%CI[-1.77,-1.02],Plt;0.000 01), joint fluid(Plt;0.000 01) and paw plasma(P=0.02), and also reduce the expression levels of TNF-α in RA animal model group. Compared with MTX alone, Tripterygium Glycosides Tablets alone reduced the same levels of TNF-α(P=0.42) and IL-6(P=0.08) in joint fluid, while Tripterygium Glycosides Tablets combined with MTX could further reduce the levels of IL-6(P=0.000 1) in joint fluid; compared with LEF alone, Tripterygium Glycosides Tablets have the similar effects on reducing the expression levels of peripheral blood TNF-α(P=0.16), IL-1β(P=0.32), IL-6(P=0.12), while Tripterygium Glycosides Tablets combined with LEF could further reduce the expression levels of TNF-α(P=0.008), IL-1β(P=0.02), IL-6(Plt;0.000 1) in peripheral blood. Therefore, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of pro-inflammatory cytokines in peripheral blood of RA patients. Tripterygium Glycosides Tablets alone could reduce the expression levels of pro-inflammatory cytokines in peripheral blood and local joint of RA animal models. Tripterygium Glycosides Tablets combined with MTX or LEF could further reduce the express levels of pro-inflammatory cytokines in peripheral blood of RA animal models. Due to the limitation of literature, this conclusion needs to be further validated.

Hierarchical organic-inorganic nanocomposites derived from polyethersulfone (PES) nanofibrous membranes with a post-modification of dopamine (DA) and polyethylenimine (PEI), comprising a high content (33 wt%) of MgO nanoparticles of smaller dimensions (12.7 ± 3.0 nm), were successively fabricated using electrospinning and DA/PEI self-polymerization methods. The obtained hybrid membranes have a rapid capture and great destructive capacity towards paraoxon-ethyl toxin degradation with a relatively short interaction time (up to 92% within 40 min) for effective environmental remediation.

A Gram-stain-negative, aerobic, motile bacterial strain, shQ-4T, was isolated from a pear tree in Henan Province, China. The strain grew at 10–41 °C, at pH 4.0–8.0 and in the presence of 1–3 % (w/v) NaCl. It shared highest 16S rRNA gene sequence similarity (96.66 %) with Herbaspirillum chlorophenolicum CPW301T. The phylogenetic tree based on 16S rRNA gene sequences showed that strain shQ-4T formed a distinct branch next to reference species in the genus Herbaspirillum . The profile of major polar lipids of strain shQ-4T contained phosphatidylethanolamine (PE), diphosphatidylglycerol (DPG), phosphatidylglycerol (PG) and an unidentified aminophospholipid (APL). The major respiratory quinone was Q-8. The major fatty acids of this strain were C16 : 0, summed feature 3 (C16 : 1ω6c/C16 : 1ω7c), C17 : 0 cyclo and C18 : 0. Strain shQ-4T is considered to represent a novel species of the genus Herbaspirillum , with the proposed name Herbaspirillum piri sp. nov. The type strain is shQ-4T (=CFCC 14641T=KCTC 52804T).

Linear detection algorithms require a series of sequential and complex process that needs high-performance processors to reduce computing time when the software is implemented. In this paper, we design a linear detection hardware accelerator with parallel computing capability through our proposed pipelined multiprocessor system-on-a-chip (SoC) design methodology; it contains an upper pipelined controller that controls the operation of the underlying Canny edge detection module and the Hough transform module. That is, we first use the edge detection module to get the edge information, and then use Hough transform to improve the accuracy of linear detection results. Finally, the pipeline control is adopted to enhance the effectiveness of the module. Based on the Canny process and the Gaussian blurring method, this study can reduce the false detection caused by noise, and decrease the number of operations and resource usage without affecting the straight line detection. Compared with Xu and Chen [14] [21] [34] [35], the proposed method can reduce 84% and 74% of the circuit resources, respectively. The hardware function circuit generated from our methodology has a good decentralized architecture and scalability, and it is easier to use in all kinds of embedded systems.

Skin photoaging (SP) is a premature skin-aging damage after repeated exposure to ultraviolet (UV) radiation, mainly characterized by oxidative stress and inflammatory disequilibrium, which makes skin show the typical symptoms of photoaging such as coarse wrinkling, dryness, irregular pigmentation and laxity. Chitosan oligosaccharide (COS), a natural polysaccharide with good humectant property, is the depolymerized product of chitosan with various biological activities, among which the antioxidant and anti-inflammatory effects have been frequently reported in recent years. However, no existing invivo study indicates whether COS has direct protective effect on UV-induced SP. In the current research, we investigated the potential preventive effect of COS against UV-caused damage in hairless mouse dorsal skin. The data showed that COS, by topical application after each UV-radiation for 10weeks, effectively inhibited the undesirable changes on the skin induced by UV. To be specific, COS obviously alleviated the macroscopic and histopathological damages of mice skin, via mitigating the disrupted collagenous fibers, as well as improving the relative content of type I collagen and the amount of total collagen. Furthermore, COS effectively inhibited the levels of pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6, and markedly improved the activities of antioxidant enzymes (SOD, GSH-Px, CAT), as well as the content of skin hydroxyproline and moisture. These findings demonstrated that this natural polysaccharide attenuated UV-induced SP, at least in part, by virtue of favorable regulation of antioxidant and anti-inflammatory status, which presumably worked in concert to maintain the morphology and level of dermal collagen.

Background Depression is a common complication after stroke and is closely related to the poor prognosis of stroke. Antidepressants are the priority drug in the treatment of post-stroke depression (PSD), but there are dependence and adverse reactions. Danzhi Xiaoyao Powder has a good effect on depression without obvious adverse reactions. At present, there is a lack of rigorous randomized controlled trials to evaluate the clinical efficacy of Danzhi Xiaoyao Powder in the treatment of PSD. Methods This is a prospective, randomized, double-blind, parallel controlled trial to explore the efficacy and safety of Danzhi Xiaoyao Powder in the treatment of PSD. The participants were randomly divided into treatment group and control group. The treatment group used Danzhi Xiaoyao Powder combined with escitalopram oxalate, and the control group used Danzhi Xiaoyao Powder simulant combined with citalopram oxalate. The two groups were both treated for 8 weeks and followed up for 3 months. Observational index includes: Total response rate, Hamilton depression scale, Barthel index, national institutes of health stroke scale, the modified Edinburgh-Scandinavian stroke scale, Incidence of adverse reactions. Finally, SPASS 22.0 software was used for statistical analysis of the data. Discussion This study will evaluate the clinical efficacy of Danzhi Xiaoyao Powder in the treatment of PSD. The results of this study will provide reliable evidence for the clinical use of Xiaoyao Powder in the treatment of PSD. Trial registration Open Science Framework Registration number: DOI 10.17605/OSF.IO/5V926.

Two Gram-stain-negative, facultatively anaerobic, motile bacterial strains isolated from symptomatic bark of Populus × euramericana canker in China were investigated using a polyphasic approach, including 16S rRNA gene sequencing, multilocus sequence analysis, and biochemical and physiological assays. 16S rRNA gene sequencing indicated that these strains belonged to the genus Brenneria , family Pectobacteriaceae , and had the highest sequence similarity with Brenneria populi CFCC 11963T (98 %). DNA–DNA hybridization experiments revealed DNA–DNA relatedness values of 72.1–78.2 % between the new isolates and strains of B. populi , revealing that these strains belonged to the same species. The 16S rRNA gene sequencing and multilocus sequence analysis suggested that the two novel strains and those of B. populi are phylogenetically closely related but form two clearly separated subgroups. Based on the data, the two novel isolates represent a subspecies of B. populi for which the name B. populi subsp. brevivirga subsp. nov. is proposed with D8-10-4-5T (=CFCC 11935T=KCTC 42841T) as the type strain, with the automatic creation of B. populi subsp. populi subsp. nov. (type strain D9-5T=CFCC 11963T=KCTC 42088T).

To reveal the force mechanism for therapeutic effect of pushing manipulation with one-finger meditation.A total of 15 participants were recruited in this study and assigned to an expert group, a skilled group and a novice group, with 5 participants in each group. Mechanical signals were collected from a biomechanical testing platform, and these data were further observed via similarity analysis and cluster analysis.Comparing the force waveforms of manipulation revealed that the manipulation forces were similar between the expert group and the skilled group (P0.05). The mean value of vertical force was 9.8 N, and 95% CI rang from 6.37 to 14.70 N, but there were significant differences compared with the novice group (P0.05). The result of overall similarity coefficient cluster analysis showed that two kinds of manipulation forces curves were existed between the expert group and the skilled group.Pushing manipulation with one-finger meditation is a kind of light stimulation manipulation on the acupoint, and force characteristics of double waveforms continuously alternated during manual operation.

Two cellulose nanocrystals (CNCs) with different aspect ratios in dimension derived from raw microcrystalline cellulose were prepared and presented in this paper. The morphological features of nanostructures were explored with TEM. Then the structure analysis, surface charge and thermal degradation behavior of CNCs were characterized and determined by FTIR/X-ray diffraction, zeta potential and TGA, respectively. Furthermore, the hybrid CNCs nano-composite membranes were facilely fabricated via vacuum-dewatered process for effective removal of cationic dyes (up to 99.9% removal of methylene blue at 10 mg/L and 97.9% removal of rhodamine B at 20 mg/L). The mechanism of such effective cationic dye removal is derived from the combined effect of both electrostatic interaction and steric hindrance between the CNC composite membrane and the cationic dyes during the filtration process. In addition, the permeation flux and dye removal efficacy of the composite membrane are CNCs loading-concentration dependent.

To systematically review the improvement effects of Tripterygium Glycosides Tables( TGT) alone or in combination with methotrexate( MTX) on the clinical signs and symptoms of rheumatoid arthritis( RA),and provide a basis for the rational use of TGT in clinic,in the current study,six literature databases including CNKI,Wan Fang,VIP,PubMed,EMbase,and Cochrane Library,were systematically searched,according to the inclusion and exclusion criteria. Review Manager 5.3 software was used to input the literatures,and we assessed the risk bias on the level of outcome indicators for each included literature. A total of 18 literatures were included,and the classification results showed that: compared with MTX,TGT alone can reduce the number of joint swelling( MD =0. 18,95%CI[-1.06,1.42],P = 0.78) and joint tenderness( MD =-0.06,95% CI[-1.69,1.56],P = 0.94) in RA patients with the same effect as MTX. In terms of drug combination,TGT combined with MTX had an advantage over MTX alone in lessening the morning stiffness time( MD = 18. 24,95% CI[12. 64,23. 84],P0. 000 01) of RA,joint tenderness( MD = 2. 65,95% CI[1. 85,3. 44],P0.000 01) and joint swelling( MD = 3.01,95% CI[2.09,3.39],P0.000 01). In conclusion,this Meta-analysis suggest that TGT alone was superior to MTX in improving joint swelling and tenderness in RA patients,TGT combined with MTX may improve the clinical manifestation of RA patients better than MTX alone.