Exploring the Path of Implementing the Home-School Co-education Model from the Perspective of Moral Education Field

As a social psychological field derived from the concept of physical field,the moral education field plays a very important role in guiding the construction of a home-school co-education model.In this paper,by analyzing the internal power system of the moral education field,with a policy oriented approach and combined with contemporary factors,it aims to empower the traditional home-school co-education model.Only by combining home education and school education,supplemented by social policy guidance,strengthening the construction of the"trinity"community,creating a harmonious and stable ecological interactive moral education field,expanding the path of home-school cooperation,strengthening the boundary of home and school responsibility,and innovating the form of home-school co-education,can it support the bright future of education.

Autumn migration routes of fledgling Chinese Egrets(Egretta eulophotes)in Northeast China and their implications for conservation

The Chinese Egret(Egretta eulophotes)is a globally threatened bird species living on the coast and islands of Liaoning,northeastern China,mainly in summer.To further protect the breeding population of Chinese Egrets,it is important to understand the current protection status of their distribution sites at pre-migration period and migration routes.Thirty-three individuals were tagged with satellite transmitters at Fantuo Island in Changhai and Xingren Island in Zhuanghe,Liaoning Province,northeastern China,in July of 2016,2017,and 2018,to identify important distribution sites during the pre-migration period,as well as detailed migration routes.The results showed that coastal mudflats in Liaoning and the west coast of North Korea were important feeding and roosting sites for fledgling Chinese Egrets from August to September.The home range sizes in August were significantly larger than in September.The eastern coast from Shandong to Guangdong,as well as Taiwan,China,and Manila Bay and Galileo Islands in the Philippines,were important stopover sites during fall migration.Specifically,we found that the egrets’autumn migration could be divided into four routes,i.e.,sea-crossing migration(SCM),coastal migration(CM),inland migration(IM),and mixed migration(MM).The migration distance,timing,speed,and straightness of the four routes also differed.The SCM routes were the straightest,and had the fastest migration speed and shortest travel time,while the IM routes had the lowest straightness and speed,and the longest duration.Manila Bay and Bohol Island in the Philippines,the west coast of Tanintharyi in Myanmar,and the Zengwun River Estuary in Taiwan,China,were wintering sites.Our findings on the key distribution sites along pre-migration and fall migration routes,including some stopover sites,have important implications for the conservation of and global action plan development for the vulnerable Chinese Egret.

Z世代大学生“慢就业”成因分析与对策探究——以地方工科院校山东省J大学为例

Z世代大学生“慢就业”现象是多元化就业价值取向的外在表现。高校专业教育与市场供需之间脱节、就业指导工作机制与大学生就业需求之间存在差距、大学生的就业能力与招聘岗位需求之间存在落差、大学生的就业观念与激烈竞争环境之间存在错位是形成这一现象的主要原因。从就业优先导向出发,高校要将专业教育、思政教育与职业教育深度融合,创新人才培养模式;构建全方位就业指导体系,提供坚实就业制度保障;搭建“互联网+”就业服务平台,提高就业服务实效;深化校企合作,提升大学生就业能力;加强家校协同,转变大学生就业观念,从而实现Z世代大学毕业生充分且高质量就业。

Migration routes of the endangered Oriental Stork(Ciconia boyciana)from Xingkai Lake,China,and their repeatability as revealed by GPS tracking

The Oriental Stork(Ciconia boyciana)is listed as'Endangered'on the International Union for the Conservation of Nature(IUCN)Red List of Threatened Species and is classified as a first category nationally protected bird species in China.Understanding this species'seasonal movements and migration will facilitate effective conservation to promote its population.We tagged 27 Oriental Stork nestlings at Xingkai Lake on the Sanjiang Plain in Heilongjiang Province,China,used GPS tracking to follow them over the periods of 2014-2017 and 2019-2022,and confirmed their detailed migratory routes using the spatial analysis function of ArcGIS 10.7.We discovered four migration routes during autumn migration:one common long-distance migration route in which the storks migrated along the coastline of Bohai Bay to the middle and lower reaches of the Yangtze River for wintering,one short-distance migration route in which the storks wintered in Bohai Bay and two other migration routes in which the storks crossed the Bohai Strait around the Yellow River and wintered in South Korea.There were no significant differences in the number of migration days,residence days,migration distances,number of stopovers and average number of days spent at stopover sites between the autumn and spring migrations(P>0.05).However,the storks migrated significantly faster in spring than in autumn(P=0.03).The same individuals did not exhibit a high degree of repetition in their migration timing and route selection in either autumn or spring migration.Even storks from the same nest exhibited considerable between-individual variation in their migration routes.Some important stopover sites were identified,especially in the Bohai Rim Region and on the Songnen Plain,and we further explored the current conservation status at these two important sites.Overall,our results contribute to the understanding of the annual migration,dispersal and protection status of the endangered Oriental Stork and provide a scientific basis for conservation decisions and the development of action plans for this species.

Resilience mediates the association between alexithymia and stress in Chinese medical students during the COVID-19 pandemic

Background Evidence indicates that medical students have had high rates of mental health problems,especially during the COVID-19 pandemic,which could be affected by alexithymia—a marked dysfunction in emotional awareness,social attachment and interpersonal relationships—and stress.However,psychological resilience might relieve alexithymia and stress levels.Aims This study aimed to investigate the role of resilience in alexithymia and stress in medical students.Methods A total of 470 medical students completed online and offline surveys,including the Toronto Alexithymia Scale-20(TAS-20),the Connor-Davidson Resilience Scale(CD-RISC)and the College Student Stress Questionnaire(CSSQ).The data of five participants were excluded because of a lack of integrity.Mann-Whitney U test or Kruskal-Wallis test was used to compare group differences in the CD-RISC scores among categorical variables.Spearman correlation analysis was employed to evaluate the associations between resilience and alexithymia and between resilience and stress.Mediation analysis was used to test the mediating effect of resilience between alexithymia and stress.Results Of the medical students considered in the analysis,382(81.28%)were female and 88(18.72%)were male.There was a significant negative correlation between the TAS-20 scores and the total and subtotal CD-RISC scores(p<0.001).The CSSQ scores also significantly negatively correlated with the total and subtotal CD-RISC scores(p<0.001).Resilience mediated the relationship between alexithymia and stress(total effect=1.0447,p<0.001).The indirect effect of alexithymia significantly impacted stress through resilience(effect=0.1670,95%CI:0.069 to 0.281).Conclusions Our findings suggest that resilience might effectively reduce alexithymia and stress.They also contributed to a better understanding of the mediating effects of resilience on alexithymia and stress during the COVID-19 pandemic.The evidence from these results encourages universities to focus on improving students’resilience.

Chemical constituents isolated from the aerial parts of Swertia pseudochinensis and their potential neuroprotective effects

Objective:Swertia pseudochinensis,an annual herb of the genus Swertia in the family Gentianaceae.Some constituents and extracts from the Swertia genus have been recently reported to possess neuroprotective effects,suggesting their potential utility in the prevention and treatment of Parkinson disease(PD).The aim of this work is to identify the chemical constituents and evaluate the potential biological activists of Swertia pseudochinensis.Methods:The phytochemicals from the aerial parts of S.pseudochinensis were isolated and purified by silica gel,Sephadex LH-20 gel,semi-preparative high-performance liquid chromatography,and identified by the spectroscopic methods.All compounds were evaluated for their potential neuroprotective effects against 1-methyl-4-phenylpyridinium-induced apoptosis in the SH-SY5Y human neuroblastoma cell line using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay.Then,we performed an enrichment analysis using the Database for Annotation,Visualization,and Integrated Discovery and investigated the mechanisms by which bellidifolin regulates neurodegenerative disease.Results:Two new anthraquinone,1,5,6-trimethoxy-2-hydroxy-3-methy-anthraquinone(1)and 1,5,6,8-tetramethoxy-2-hydroxy-3-methyanthraquinone(2),together with nine known including 7-O-b-d-glucopyranosyl-1,8-dihydroxy-3-methoxyxanthone(3),gentisin(4),swertianolin(5),bellidifolin(6),gentiacaulein(7),norswertianolin(8),5-O-b-d-glucopyranosyl-1,3,8-trihydroxyapatone(9),1-hydroxy-3,5,8-trimethoxyxanthone(10),and aurantio-obtusin(11),were isolated and compounds 6–8 and 10 exhibited neuroprotective effects at a concentration of 50mmol/L.Among them,bellidifolin showed significant protective activity,and might have potential as a neuroprotective agent for the treatment of PD,possibly by acting on oxidative damage and reactive oxygen species.Conclusions:These findings indicate that further research on the genus Swertia and its bioactive constituents toward neurodegenerative disorders could be extremely rewarding.

SARS-CoV-2:structure,host,virus source and pathogenesis

Cancer is a serious threat to human life and a big problem in clinical treatment.Some natural active substances extracted from Traditional Chinese Medicine can effectively inhibit the growth of cancer cells,which is a new direction for finding more effective anticancer drugs.Osthole is a natural coumarin compound extracted from Traditional Chinese Medicines such as Cnidium monnieri,Angelica pubescens and Peucedanum praeruptorum Dunn.It has significant inhibitory activity against a variety of cancers.This paper summarizes the anticancer effects and molecular mechanisms of osthole in the treatment of cancers in recent years in order to provide references for further research.

A selective HK2 degrader suppresses SW480 cancer cell growth by degrading HK2

Hexokinase 2(HK2)is the rate-limiting enzyme in the first step of glycolysis,catalyzing glucose to glucose-6-phosphate,and overexpressed in most cancer cells.HK2 also binds to voltage-dependent anion channel(VDAC)to stabilize the mitochondrial outer membrane,which inhibits cancer cell apoptosis.Therefore,HK2 has become a potential target for cancer treatment.Proteolysis targeting chimeras(PROTACs)are hetero-bifunctional molecules that recruit an E3 ubiquitin ligase to a given substrate protein resulting in its targeted degradation.Many potent and specific PROTACs targeting dissimilar targets have been developed.In this study,an HK2 PROTAC,4H-5P-M,was developed and induced the degradation of HK2 relying on the ubiquitin-proteasome system.It was found that 4H-5P-M as an effective HK2 degrader induced HK2 degradation in a dose-and time-dependent manner and suppressed the growth of SW480 cells.4H-5P-M selectively induced HK2 degradation at a lower concentration than other hexokinase isozymes.Moreover,it could suppress glycolysis and accelerate the apoptosis of cancer cells.Therefore,it provided a new insight into the development of anti-tumor drugs.

Design,synthesis and evaluation of the first DYRK1A degrader for promoting the proliferation of pancreaticβ-cells

Dual-specificity tyrosine-phosphorylation-regulated kinase 1A(DYRK1A)is the most promising target for diabetes treatment by promotingβ-cell proliferation.The desmethylbellidifolin(DMB)as a DYRK1A inhibitor could facilitateβ-cell proliferation in vivo and in vitro.However,DMB has the problem of weak binding affinity to DYRK1A,which means that continuous high concentration administration of DMB is effective for the diabetes.In order to solve this problem,we designed and synthesized a series of DMBbased proteolysis targeting chimeras(PROTACs)by taking advantage of the property of PROTAC that induce protein degradation in a cycle-catalytic manner.MDM2-based PROTAC X1-4P-MDM2 was identified as the most active PROTAC molecule.Mechanism research showed that X1-4P-MDM2 formed a ternary complex with DYRK1A and murine double minute 2(MDM2),and induced the degradation of DYRK1A through the ubiquitin-proteasome system pathway.At a dose much lower than that of DMB,X1-4PMDM2 still significantly enhancedβ-cell proliferation by inhibiting transforming growth factor beta(TGF-β)and promoting the mitogen-activated protein kinases/extracellular signal-regulated kinase(MAPK/ERK)signaling pathway,which may provide a new strategy for the application of DMB in diabetes.

Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods

SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths.There are currently no registered therapies for treating coronavirus infections.Because of time consuming process of new drug development,drug repositioning may be the only solution to the epidemic of sudden infectious diseases.We systematically analyzed all the proteins encoded by SARS-CoV-2 genes,compared them with proteins from other coronavirnses,predicted their structures,and built 19 structures that could be done by homology modeling.By performing target-based virtual ligand screening,a total of21 targets(including two human targets)were screened against compound libraries including ZINC drug database and our own database of natural products.Structure and screening results of important targets such as 3-chymotrypsin-like protease(3 CLpro),Spike,RNA-dependent RNA polymerase(RdRp),and papain like protease(PLpro)were discussed in detail.In addition,a database of 78 commonly used antiviral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed.Possible targets of these compounds and potential drugs acting on a certain target were predicted.This study will provide new lead compounds and targets for further in vitro and in vivo studies of SARS-CoV-2,new insights for those drugs currently ongoing clinical studies,and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.

Andrographolide and Its Derivative Potassium Dehydrographolide Succinate Suppress PRRSV Replication in Primary and Established Cells via Differential Mechanisms of Action

Porcine reproductive and respiratory syndrome virus(PRRSV) continues to cause significant economic loss worldwide and remains a serious threat to the pork industry. Currently, vaccination strategies provide limited protection against PRRSV infection, and consequently, new antiviral strategies are urgently required. Andrographolide(Andro) and its derivative potassium dehydrographolide succinate(PDS) have been used clinically in China and other Asian countries as therapies for inflammation-related diseases, including bacterial and viral infections, for decades. Here, we demonstrate that Andro and PDS exhibit robust activity against PRRSV replication in Marc-145 cells and primary porcine alveolar macrophages(PAMs). The two compounds exhibited broad-spectrum inhibitory activities in vitro against clinically circulating type 2 PRRSV GD-HD, XH-GD, and NADC30-like HNhx strains in China. The EC_(50)values of Andro against three tested PRRSV strain infections in Marc-145 cells ranged from 11.7 to 15.3 lmol/L, with selectivity indexes ranging from 8.3 to10.8, while the EC_(50)values of PDS ranged from 57.1 to 85.4 lmol/L, with selectivity indexes ranging from 344 to 515.Mechanistically, the anti-PRRSV activity of the two compounds is closely associated with their potent suppression on NFj B activation and enhanced oxidative stress induced by PRRSV infection. Further mechanistic investigations revealed that PDS, but not Andro, is able to directly interact with PRRSV particles. Taken together, our findings suggest that Andro and PDS are promising PRRSV inhibitors in vitro and deserves further in vivo studies in swine.

PROTAC technology as a novel tool to identify the target of lathyrane diterpenoids

To the Editor:Proteolysis Targeting Chimera(PROTAC)is an emerging approach to selectively degrading target proteins by utilizing endogenous proteasome.Since PROTACs can degrade target proteins without high affinity,it is natural to speculate that this technology can be used to identify the targets of natural products。Although a recent study reported the employment of PROTACs to explore the unknown non-kinase target of a multi-kinase inhibitor sorafenib,whether PROTACs can be used to find the potential targets of natural products remains unexplored.

Design,synthesis,and evaluation of PD-L1 degraders to enhance T cell killing activity against melanoma

Inhibitor targeting immune checkpoint is a promising new anticancer therapy.Blocking the interaction between PD-1 and PD-L1 can reverse the immunosuppression state and improve the lethality of immune cells to tumor cells.Here,we report PROTAC-based PD-L1 degraders to enhance T cell killing activity against melanoma.Four series of PD-L1 degraders were designed and synthesized to VHL,CRBN,MDM2 or c IAP E3 ligase system,in which CRBN-ligand-based compound BMS-37-C3 was identified as the most active PROTAC molecule.BMS-37-C3 also significantly enhanced the killing ability of T cells in a co-culture model of A375 and T cells.Furthermore,western blot data and flow cytometry demonstrated that BMS-37-C3 could reduce the protein levels of PD-L1 in dose and time dependent manner,which may provide a new therapeutic method for tumor immunotherapy.

The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer

Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy.Isocitrate dehydrogenases(IDHs)are a class of key proteins in energy metabolism,including IDH1,IDH2,and IDH3,which are involved in the oxidative decarboxylation of isocitrate to yield a-ketoglutarate(a-KG).Mutants of IDH1 or IDH2 can produce D-2-hydroxyglutarate(D-2HG)with a-KG as the substrate,and then mediate the occurrence and development of cancer.At present,no IDH3 mutation has been reported.The results of pan-cancer research showed that IDH1 has a higher mutation frequency and involves more cancer types than IDH2,implying IDH1 as a promising anti-cancer target.Therefore,in this review,we summarized the regulatory mechanisms of IDH1 on cancer from four aspects:metabolic reprogramming,epigenetics,immune microenvironment,and phenotypic changes,which will provide guidance for the understanding of IDH1 and exploring leading-edge targeted treatment strategies.In addition,we also reviewed available IDH1 inhibitors so far.The detailed clinical trial results and diverse structures of preclinical candidates illustrated here will provide a deep insight into the research for the treatment of IDH1-related cancers.

Arf6 as a therapeutic target:Structure,mechanism,and inhibitors

ADP-ribosylation factor 6(Arf6),a small G-protein of the Ras superfamily,plays pivotal roles in multiple cellular events,including exocytosis,endocytosis,actin remodeling,plasma membrane reorganization and vesicular transport.Arf6 regulates the progression of cancer through the activation of cell motility and invasion.Aberrant Arf6 activation is a potential therapeutic target.This review aims to understand the comprehensive function of Arf6 for future cancer therapy.The Arf6 GEFs,protein structure,and roles in cancer have been summarized.Comprehending the mechanism underlying Arf6-mediated cancer cell growth and survival is essential.The structural features of Arf6 and its efforts are discussed and may be contributed to the discovery of future novel protein-protein interaction inhibitors.In addition,Arf6 inhibitors and mechanism of action are listed in the table.This review further emphasizes the crucial roles in drug resistance and attempts to offer an outlook of Arf6 in cancer therapy.

Hierarchical micro-nanostructures from polyoxometalates and polydopamine:Characterization,electrochemical and intrinsic peroxidase-like properties

Hybrid composite materials with hierarchical structures have attracted continuing attention for their enhanced features and various applications.The new hybrid composites XW_(9)@PDA(XW_(9) means Na_(8)H[α-PW_(9)O_(34)],Na_(10)[α-SiW_(9)O_(34)]and Na_(10)[α-GeW_(9)O_(34)];PDA means polydopamine)have been synthesized for potential sensing applications.The effect of polyoxometalates on the formation of the hybrid composites was investigated.Scanning electron microscopy(SEM)supported the obtained XW_(9)@PDA were hierarchical microsphere.By monitoring the reaction of classical peroxidase substrate o-phenylenediamine(OPD)to form yellow 2,3-diaminophenazine(DAB)in the presence of H_(2)O_(2),the peroxidase-like activity of XW_(9)@PDA was calculated.The results showed that XW_(9)@PDA still keep the peroxidase-like activity and have 505.98%,208.58%and 582.78%enhancement in intrinsic catalytic activity for PW_(9)@PDA,SiW_(9)@PDA and GeW_(9)@PDA.Among the three composites,PW_(9)@PDA showed the highest peroxidase-like activity.Therefore,PW_(9)@PDA was applicable to the colorimetric and electrochemical sensing for H_(2)O_(2).

Cloud-Data Envelopment Analysis Method Used for Assessment of Restoration Building Block Schemes

The selection of an optimized restoration building block(RBB)scheme among all available schemes is one of the most important factors impacting the power system restoration process after a complete or partial blackout.This paper presents a data envelopment analysis(DEA)model used as an empirical method to assess the RBB schemes.An N-level evaluation scale cloud system is built based on cloud theory to transform qualitative I/O indices of DEA model into quantitative values.Through joint utilization of the CCR(Charnes,Cooper and Rhodes)model and the LJK(Li,Jahanshahloo and Khodabakhshi)model,the established Joint-DEA model makes the newly proposed Cloud-DEA method a more feasible and robust method in assessment of RBB schemes.

SESQUITERPENES FROM CURCUMA PHAEOCAULIS AND THEIR INHIBITORY ACTIVITIES ON NITRIC OXIDE PRODUCTION IN RAW 264.7 CELLS

Curcumfa phaeocaulis Valeton is used in traditional Chinese medicines for the treatment of blood-related disorders such as blood stasis and inflammation.Our previous studies have found that sesquiterpenes were mainly isolated from C.wenyujin and C.phaeocaulis,while diarylheptanoids were the major compounds from C.kwangsiensis.And most of the isolated compounds exhibited remarkable

Double-cavity nor-seco-cucurbit[10]uril-based supramolecular assembly for selective detection and removal of trinitrophenol

The effective removal and selective detection of explosive and toxic pollutant trinitrophenol (TNP) is an attractive but challenging field.Herein,a double-cavity nor-seco-cucurbit[10]uril (ns-Q[10])-based supramolecular assembly 8-HQ@ns-Q[10]was fabricated and its structure was characterized by X-ray single crystal diffraction.In this assembly,the stoichiometric ratio of ns-Q[10]and 8-hydroxyquinoline (8-HQ) is 1:2,which is also attributed to the special double-cavity structure of ns-Q[10].The luminescence sensing experiments showed that 8-HQ@ns-Q[10]can be used as a good fluorescence-enhanced sensing material (enhanced 27-fold) for the rapid detection of explosives and the aqueous contaminant TNP,with a limit of detection (LOD) of 2.07×10^(-5)mol/L,without interference from other phenolic compounds.Furthermore,TNP can be efficiently removed in the presence of assembly 8-HQ@ns-Q[10],and the removal efficiency is more than 89%.Therefore,the supramolecular assembly 8-HQ@ns-Q[10],as a fluorescenceenhanced luminescence sensor and adsorption material,has rich research value and potential application prospect when applied to the detection and removal of TNP in aqueous environment.

Developing potent BTK^(C481S)PROTACs for ibrutinib-resistant malignant lymphoma

Ibrutinib is a first-line treatment drug for B-cell malignancies.However,resistance to ibrutinib has been reported due to BTKC481Smutation.Although PROTAC strategy is expected to overcome this clinical resistance,it has limitations such as large molecular weight and moderate bioactivity,which restrict its potential clinical application.Herein,we report a new type of potent BTKC481S-targeting PROTAC degrader.Through design,computer-assisted optimization and SAR studies,we have developed a representative BTKC481Sdegrader L6 with a much smaller molecular weight and improved solubility.Notably,L6 demonstrates better BTK degrading activity and lower IC50value in ibrutinib-resistant cell line than the first-generation BTK degrader P13I.Optimization strategy of L6 provides a general approach in the development of PROTACs targeting BTK and other proteins for future study.