教育现代化目标下普通化学“四化”教学模式探析

结合课程知识结构特点构建“化学原理系统化、化学知识有用化、化学应用善恶化、前沿基础融合化”的普通化学全周期“四化”课程教学模式,系统化落实立德树人根本任务,在教学实践中使学生逐步形成学习化学“明物质形成变化之理”的化学素养、“增民物和谐共生之信”的理想信念、“崇人生徙善远罪之德”的人生哲学、“力时代‘双碳’使命之行”的责任担当,实现了普通化学课程思政与党史学习教育同向同行、同频共振,助力大学教育为党育人、为国育才的目标实现。

杂原子(Zr,Y)掺杂的铈基催化剂中氧物种与其催化CH_3SH分解的活性/稳定性之间的关系（英文）

铈基催化剂因其优异的储放氧能力被广泛地应用于多种催化反应.铈基材料作为催化剂在CH_3SH(甲硫醇)分解反应中的应用也因其产物简单、易处理而受到越来越多的关注.本课题组在前期研究中发现,纳米二氧化铈在CH_3SH催化分解反应中表现出较高的催化活性,然而催化剂却在很短时间内快速失活.为进一步提高铈基氧化物的稳定性,我们通过引入稀土元素对氧化铈催化剂进行改性,结果发现其稳定性明显提高;同时催化剂稳定性与氧空位数量有关,氧空位数量越多,催化剂越稳定.然而,目前关于氧空位对催化CH_3SH分解反应的具体作用,CH_3SH在铈基材料上的失活机理以及氧物种与催化行为之间的相互关系尚不清楚.因此,有必要进一步研究氧空位对提高催化稳定性的贡献并揭示催化行为与氧物种之间的相互关系.本文通过微波辅助柠檬酸络合法制备一系列杂原子(Zr,Y)掺杂的铈基催化剂CeO_2,Ce_(1-x)Z_rxO_2,Ce_(1-x)Y_xO_2-δ(x=0.25,0.50,0.75,1.00),通过考察锆、钇杂原子价态和离子半径对CH_3SH催化分解活性和稳定性的影响来探索铈基催化剂中氧空位的作用及氧物种与催化行为之间的关系.其中,氧物种与催化行为之间的关系可包括两类:(1)表面晶格氧与催化活性之间的关系;(2)体相晶格氧迁移与催化稳定性之间的关系.催化性能和表征结果表明,铈基氧化物中表面晶格氧对CH_3SH催化转化起着至关重要的作用.Ce_(0.75)Zr_(0.25)O_2在CH_3SH的催化分解中表现出更高的催化活性,这是由于Ce_(0.75)Zr_(0.25)O_2有更多的表面晶格氧、活性氧物种及良好的氧化还原性能.Ce_(0.75)Y_(0.25)O_2-δ也表现出更好的催化稳定性,这是由于催化剂中有更多的氧空位,它们会促进体相晶格氧迁移到催化剂表面以补充表面晶格氧.此外,Ce与杂原子之间化学价差极大地影响着表面晶格氧含量以及催化剂中体相氧的迁移率,进而影响铈基催化剂的活性和稳定性.

On the improved tensile strength and ductility of Mg-Sn-Zn-Mn alloy processed by aging prior to extrusion

This study investigated the influence of aging prior to extrusion(APE)on the tensile strength and ductility of as-extruded Mg-8.32Sn-1.85Zn-0.17Mn alloy.Results demonstrated that APE treatment dramatically increased the volume fraction of recrystallized grains,thereby decreasing the grain size of the as-extruded alloy.This phenomenon was primarily attributed to the particle-stimulated nucleation and pinning effect induced by large amounts of small Mg 2 Sn precipitates produced by the APE treatment and dynamic precipitation.The tensile yield strength increased from 242.4 MPa to 256.5 MPa after APE treatment.The improved tensile strength can be attributed to the enhanced grain boundary strengthening and precipitation strengthening.The ductility of the as-extruded alloy also markedly increased from 7.1%to 13.5%after the APE treatment.The improved ductility of APE alloy was attributed to the texture randomization,the activity of pyramidal<c+a>slip and the suppressed formation of{10-11}contraction twins and coarse Mg 2 Sn phases.

Application of photodynamic therapy in cancer: challenges and advancements

Although great achievements have been made in the past decades in medicine,cancer remains a worldwide public health issue.Surgery is usually accompanied by shortcomings such as residual lesions and poor treatment effects,and the successive appearance of other treatment methods,such as radiotherapy and chemotherapy,has not changed the postoperative recurrence rate,toxicity,and side effects.However,the advent of photodynamic therapy has greatly improved this situation.Photodynamic therapy is an emerging tumor diagnosis and treatment technology with good application prospects,photodynamic therapy uses a specific wavelength of light to excite a photosensitizer to generate reactive oxygen species,damage tumor blood vessels and promote tumor cell apoptosis,exerting an anti-tumor effect.Photodynamic therapy has become a new clinical anti-tumor therapy due to its clear efficacy,few side effects,and easy use in combination with other therapies.In this review,we summarized the main mechanism,current challenges,and advancements of photodynamic therapy.

3D-Printed Scaffolds Promote Angiogenesis by Recruiting Antigen-Specific T Cells

The immune response after implantation is a primary determinant of the tissue-repair effects of threedimensional(3D)-printed scaffolds.Thus,scaffolds that can subtly regulate immune responses may display extraordinary functions.Inspired by the angiogenesis promotion effect of humoral immune response,we covalently combined mesoporous silica micro rod(MSR)/polyethyleneimine(PEI)/ovalbumin(OVA)self-assembled vaccines with 3D-printed calcium phosphate cement(CPC)scaffolds for local antigen-specific immune response activation.With the response activated,antigen-specific CD4+T helper2(Th2)cells can be recruited to promote early angiogenesis.The silicon(Si)ions from MSRs can accelerate osteogenesis,with an adequate blood supply being provided.At room temperature,scaffolds with uniformly interconnected macropores were printed using a self-setting CPC-based printing paste,which promoted the uniform dispersion and structural preservation of functional polysaccharides oxidized hyaluronic acid(OHA)inside.Sustained release of OVA was achieved with MSR/PEI covalently attached to scaffolds rich in aldehyde groups as the vaccine carrier.The vaccine-loaded scaffolds effectively recruited and activated dendritic cells(DCs)for antigen presentation and promoted the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.When embedded subcutaneously in vivo,the vaccine-loaded scaffolds increased the proportion of Th2 cells in the spleen and locally recruited antigenspecific T cells to promote angiogenesis in and around the scaffold.Furthermore,the result in a rat skull defect-repair model indicated that the antigen-specific vaccine-loaded scaffolds promoted the regeneration of vascularized bone.This method may provide a novel concept for patient-specific implant design for angiogenesis promotion.

Aptamers targeting SARS-CoV-2 nucleocapsid protein exhibit potential ant1ip1 an-coronavirus activity

Emerging and recurrent infectious diseases caused by human coronaviruses(HCoVs)continue to pose a significant threat to global public health security.In light of this ongoing threat,the development of a broad-spectrum drug to combat HCoVs is an urgently priority.Herein,we report a series of anti-pan-coronavirus ssDNA aptamers screened using Systematic Evolution of Ligands by Exponential Enrichment(SELEX).These aptamers have nanomolar affinity with the nucleocapsid protein(NP)of Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and also show excellent binding efficiency to the N proteins of both SARS,MERS,HCoV-OC43 and-NL63 with affinity KD values of 1.31 to 135.36 nM.Such aptamer-based therapeutics exhibited potent antiviral activity against both the authentic SARS-CoV-2 prototype strain and the Omicron variant(BA.5)with EC50 values at 2.00 nM and 41.08 nM,respectively.The protein docking analysis also evidenced that these aptamers exhibit strong affinities for N proteins of pan-coronavirus and other HCoVs(−229E and-HKU1).In conclusion,we have identified six aptamers with a high pan-coronavirus antiviral activity,which could potentially serve as an effective strategy for preventing infections by unknown coronaviruses and addressing the ongoing global health threat.

Averrhoa carambola extractive inhibits breast cancer via regulating CEPT1 and LYPLA1

Liposomes have been widely exploited as a drug delivery system in treating tumors because of their advantage to enhance anti-tumor efficacy and reduce side effects. In this study, the tumor-targeted 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione(DMDD, i.e., Averrhoa carambola extractive) liposomes(HA/TN-DLP) were conducted and assessed. HA/TN-DLP showed controllable drug loading(up to 83%)with high stability. In vitro and in vivo studies showed good cell uptake behavior and high inhibition rate of breast cancer compared to free DMDD. HA/TN-DLP might be the suitable for DMDD due to its better advantages in delivery, penetrability, and targeting-tumor capability. For in vivo mouse model tests,HA/TN-DLP effectively inhibited tumor growth compared to free DMDD. Further analyses indicated that HA/TN-DLP inhibited the glycerophospholipid metabolism pathway by reducing the biosynthesis of phosphatidylcholine and 1-acyl-sn-glycero-3-phosphocholine through regulating the expressions of CEPT1 and LYPLA1, and inhibited tumor cell growth by regulating the PI3K/Akt and NF-κ B signaling pathways. In conclusion, the obviously enhanced antitumor effect further demonstrated that HA/TN-DLP may be a promising tumor-targeting agent.

Bamboo‑Inspired Gasotransmitter Microfibres for Wound Healing

Diabetic wounds have become a major clinical problem that cannot be ignored.Gases,such as hydrogen sulphide(H_(2)S),have demonstrated value in inducing angiogenesis and accelerating wound healing,while their effective delivery is still challenging.Here,inspired by the continuous-independent hollow structure of bamboo,we propose novel gasotransmitter microfibres with septal H_(2)S bubbles using microfluidic spinning for diabetic wound healing.Benefitting from the exact control of microfluidics,gasotransmitter microfibres with different bubble sizes and morphologies could be generated successfully and continuously.Under the dual effects of drugs in the shell and gas in the core,the wound healing process could be accelerated.Furthermore,the controllable release of drugs could be achieved by adding responsive materials into the microfiber shell,which would promote continuous effects of contents on demand.Based on in vitro and in vivo stud-ies,we have proven that these gasotransmitter microfibres have a positive impact on inducing angiogenesis and promoting cell proliferation during wound healing.Thus,it is believed that the bamboo-inspired gasotransmitter microfibres will have important value in gasotransmitter research and clinical applications.

Correction To:POD Nanozyme optimized by charge separation engineering for light/pH activated bacteria catalytic/photodynamic therapy

Correction to:Signal Transduction and Targeted Therapy https://doi.org/10.1038/s41392-022-00900-8,published online 28 March 2022 The plate photo from Control in Figure 4c of the published work was mistakenly used when editing the photos,and the corrected version is demonstrated below.The results and conclusions of this paper were not affected by this error.

Dissecting the role of AMP-activated protein kinase in human diseases

AMP-activated protein kinase(AMPK), known as a sensor and a master of cellular energy balance, integrates various regulatory signals including anabolic and catabolic metabolic processes.Accompanying the application of genetic methods and a plethora of AMPK agonists, rapid progress has identified AMPK as an attractive therapeutic target for several human diseases, such as cancer, type2 diabetes, atherosclerosis, myocardial ischemia/reperfusion injury and neurodegenerative disease. The role of AMPK in metabolic and energetic modulation both at the intracellular and whole body levels has been reviewed elsewhere. In the present review, we summarize and update the paradoxical role of AMPK implicated in the diseases mentioned above and put forward the challenge encountered. Thus it will be expected to provide important clues for exploring rational methods of intervention in human diseases.

Therapeutic siRNA:state of the art

RNA interference(RNAi)is an ancient biological mechanism used to defend against external invasion.It theoretically can silence any disease-related genes in a sequence-specific manner,making small interfering RNA(siRNA)a promising therapeutic modality.After a two-decade journey from its discovery,two approvals of siRNA therapeutics,ONPATTRO®(patisiran)and GIVLAARI™(givosiran),have been achieved by Alnylam Pharmaceuticals.Reviewing the long-term pharmaceutical history of human beings,siRNA therapy currently has set up an extraordinary milestone,as it has already changed and will continue to change the treatment and management of human diseases.It can be administered quarterly,even twice-yearly,to achieve therapeutic effects,which is not the case for small molecules and antibodies.The drug development process was extremely hard,aiming to surmount complex obstacles,such as how to efficiently and safely deliver siRNAs to desired tissues and cells and how to enhance the performance of siRNAs with respect to their activity,stability,specificity and potential off-target effects.In this review,the evolution of siRNA chemical modifications and their biomedical performance are comprehensively reviewed.All clinically explored and commercialized siRNA delivery platforms,including the GalNAc(N-acetylgalactosamine)–siRNA conjugate,and their fundamental design principles are thoroughly discussed.The latest progress in siRNA therapeutic development is also summarized.This review provides a comprehensive view and roadmap for general readers working in the field.

Application of regional citrate anticoagulation in patients at high risk of bleeding during intermittent hemodialysis:a prospective multicenter randomized controlled trial

Objective:Safe and effective anticoagulation is essential for hemodialysis patients who are at high risk of bleeding.The purpose of this trial is to evaluate the effectiveness and safety of two-stage regional citrate anticoagulation(RCA)combined with sequential anticoagulation and standard calcium-containing dialysate in intermittent hemodialysis(IHD)treatment.Methods:Patients at high risk of bleeding who underwent IHD from September 2019 to May 2021 were prospectively enrolled in 13 blood purification centers of nephrology departments,and were randomly divided into RCA group and saline flushing group.In the RCA group,0.04 g/mL sodium citrate was infused from the start of the dialysis line during blood draining and at the venous expansion chamber.The sodium citrate was stopped after 3 h of dialysis,which was changed to sequential dialysis without anticoagulant.The hazard ratios for coagulation were according to baseline.Results:A total of 159 patients and 208 sessions were enrolled,including RCA group(80 patients,110 sessions)and saline flushing group(79 patients,98 sessions).The incidence of severe coagulation events of extracorporeal circulation in the RCA group was significantly lower than that in the saline flushing group(3.64%vs.20.41%,P<0.001).The survival time of the filter pipeline in the RCA group was significantly longer than that in the saline flushing group((238.34±9.33)min vs.(221.73±34.10)min,P<0.001).The urea clearance index(Kt/V)in the RCA group was similar to that in the saline flushing group with no statistically significant difference(1.12±0.34 vs.1.08±0.34,P=0.41).Conclusions:Compared with saline flushing,the two-stage RCA combined with a sequential anticoagulation strategy significantly reduced extracorporeal circulation clotting events and prolonged the dialysis time without serious adverse events.

Selenium speciation in flue desulfurization residues

Flue gas from coal combustion contains significant amounts of volatile selenium （Se）. The capture of Se in the flue gas desulfurization （FGD） scrubber unit has resulted in a generation of metal-laden residues. It is important to determine Se speciation to understand the environmental impact of its disposal. A simple method has been developed for selective inorganic Se（IV）, Se（VI） and organic Se determination in the liquid-phase FGD residues by hydride generation atomic fluorescence spectrometry （AFS）. It has been determined that Se（IV）, Se（VI） and organic Se can be accurately determined with detection limits （DL） of 0.05, 0.06 and 0.06 μg/L, respectively. The accuracy of the proposed method was evaluated by analyzing the certified reference material, NIST CRM 1632c, and also by analyzing spiked tap-water samples. Analysis indicates that the concentration of Se is high in FGD liquid residues and primarily exists in a reduced state as selenite （Se（IV））. The toxicity of Se（IV） is the strongest of all Se species. Flue gas desulfurization residues pose a serious environmental risk.

Microstructure and Thermal Conductivity of As-Cast and As-Solutionized Mg–Rare Earth Binary Alloys

The microstructure and thermal conductivity of four groups of Mg–rare earth（RE） binary alloys（Mg–Ce,Mg–Nd, Mg–Y and Mg–Gd） in as-cast and as-solutionized states were systematically studied. Thermal conductivity was measured on a Netzsch LFA457 using laser flash method at room temperature. Results indicated that for as-cast alloys, the volume fraction of second phases increased with the increase of alloying elements. After solutionizing treatment, a part or most of second phases were dissolved in α-Mg matrix, except for Mg–Ce alloys. The thermal conductivity of as-cast and as-solutionized Mg–RE alloys decreased with the increase of concentrations. The thermal conductivity of as-solutionized Mg–Nd,Mg–Y and Mg–Gd alloys was lower than that of as-cast alloys. Thermal conductivity of as-solutionized Mg–Ce alloys was higher than that of as-cast alloys, because of the elimination of lattice defects and fine dispersed particles during solutionizing treatment. Different RE elements have different influences on the thermal conductivity of Mg alloys in the following order： Ce 〈 Nd 〈 Y 〈 Gd. Ce has the minimum effect on thermal conductivity of Mg alloys, because of the very low solubility of Ce in the α-Mg matrix. The variations in the atomic radius of the solute elements with Mg atom（ r）, valence, configuration of extranuclear electron of the solute atoms, and the maximum solid solubility of elements in the α-Mg matrix were suggested to be the main reasons for the differences in thermal conductivity of resulting Mg–RE alloys.

POD Nanozyme optimized by charge separation engineering for light/pH activated bacteria catalytic/photodynamic therapy

The current feasibility of nanocatalysts in clinical anti-infection therapy,especially for drug-resistant bacteria infection is extremely restrained because of the insufficient reactive oxygen generation.Herein,a novel Ag/Bi2MoO6(Ag/BMO)nanozyme optimized by charge separation engineering with photoactivated sustainable peroxidase-mimicking activities and NIR-II photodynamic performance was synthesized by solvothermal reaction and photoreduction.The Ag/BMO nanozyme held satisfactory bactericidal performance against methicillin-resistant Staphylococcus aureus(MRSA)(~99.9%).The excellent antibacterial performance of Ag/BMO NPs was ascribed to the corporation of peroxidase-like activity,NIR-II photodynamic behavior,and acidity-enhanced release of Ag^(+).As revealed by theoretical calculations,the introduction of Ag to BMO made it easier to separate photo-triggered electronhole pairs for ROS production.And the conduction and valence band potentials of Ag/BMO NPs were favorable for the reduction of O_(2) to·O_(2)^(−).Under 1064 nm laser irradiation,the electron transfer to BMO was beneficial to the reversible change of Mo^(5+)/Mo^(6+),further improving the peroxidase-like catalytic activity and NIR-II photodynamic performance based on the Russell mechanism.In vivo,the Ag/BMO NPs exhibited promising therapeutic effects towards MRSA-infected wounds.This study enriches the nanozyme research and proves that nanozymes can be rationally optimized by charge separation engineering strategy.

Boron difluoride formazanate dye for high-efficiency NIR-Ⅱ fluorescence imaging-guided cancer photothermal therapy

The small molecular second near-infrared(NIR-Ⅱ, 1000–1700 nm) dye-based nanotheranostics can concurrently combine deep-tissue photodiagnosis with in situ phototherapy, which occupies a vital position in the early detection and precise treatment of tumors. However, the development of small molecular NIR-Ⅱ dyes is still challenging due to the limited electron acceptors and cumbersome synthetic routes.Herein, we report a novel molecular electron acceptor, boron difluoride formazanate(BDF). Based on BDF, a new small molecular NIR-Ⅱ dye BDF1005 is designed and synthesized with strong NIR-I absorption at 768 nm and bright NIR-Ⅱ peak emission at 1034 nm. In vitro and in vivo experiments demonstrate that BDF1005-based nanotheranostics can be applied for NIR-Ⅱ fluorescence imaging-guided photothermal therapy of 4T1 tumor-bearing mice. Under 808 nm laser irradiation, tumor growth can be effectively inhibited. This work opens up a new road for the exploitation of NIR-Ⅱ small molecular dyes for cancer phototheranostics.

Generation ofαGal-enhanced bifunctional tumor vaccine

Hepatocellular carcinoma(HCC)is a common malignant tumor with poor prognosis and high mortality.In this study,we demonstrated a novel vaccine targeting HCC and tumor neovascular endothelial cells by fusing recombinant MHCC97H cells expressing porcine a-1,3-galactose epitopes(a Gal)and endorphin extracellular domains(END)with dendritic cells(DCs)from healthy volunteers.END^(+)/Gal^(+)-MHCC97H/DC fusion cells induced cytotoxic T lymphocytes(CTLs)and secretion of interferon-gamma(IFN-γ).CTLs targeted cells expressing a Gal and END and tumor angiogenesis.The fused cell vaccine can effectively inhibit tumor growth and prolong the survival time of human hepatoma mice,indicating the high clinical potential of this new cell based vaccine.

A recombinant Newcastle disease virus expressing MMP8 promotes oncolytic efficacy

Oncolytic virus is an emerging anti-cancer strategy. However, extracellular matrix(ECM), as a physical barrier, limits virus spread within the tumor. To overcome the obstacle, we constructed a recombinant Newcastle disease virus(NDV) expressing matrix metalloproteinase(MMP8)(NDV-MMP8) using with reverse genetic technology. In vitro, NDV-MMP8 was identified and verified by WB and ELISA. Cell viability was detected by CCK-8 assay. In vivo, we established two liver cancer xenograft models. NDV-MMP8 was injected into the tumor to observe the tumor volume and survival of mice. The changes in extracellular matrix were observed by Masson’s trichrome staining. Virus expression in tumor tissues was detected by immunofluorescence assay. The virus titer in tumor tissues was detected by TCID50. Histopathological changes were detected by hematoxylin and eosin(HE) and terminal deoxynucleotidyl transferase d UTP nick end labeling(TUNEL) staining. Intratumoral administration of NDV-MMP8 can effectively degrade ECM, promote the spread of the virus within the tumor, and reduce tumor growth rate. Therefore, the method of increasing intratumoral virus accumulation by degradation of the ECM to enhance the oncolytic effect has great potential for clinical application.

Generation of in situ CRISPR-mediated primary and metastatic cancer from monkey liver

Non-human primates(NHPs)represent the most valuable animals for drug discovery.However,the current main challenge remains that the NHP has not yet been used to develop an efficient translational medicine platform simulating human diseases,such as cancer.This study gen erated an in situ gen e-editi ng approach to in duce efficie nt loss-of-function mutations of Pten and p53 genes for rapid modeling primary and metastatic liver tumors using the CRISPR/Cas9 in the adult cyno molgus mon key.Un der ultraso und guida nee,the CRISPR/Cas9 was injected into the cyno molgus mon key liver through the in trahepatic portal vein.The results showed that the ultraso un d-guided CRISPR/Cas9 resulted in in dels of the Pten and p53 genes in seve n out of eight monkeys.The best mutation efficiencies for Pten and p53 were up to 74.71%and 74.68%,respectively.Furthermore,the morbidity of primary and exte nsively metastatic(lung,splee n,lymph nodes)hepatoma in CRISPR-treated mon keys was 87.5%.The ultraso un d-guided CRISPR system could have great potential to successfully pursue the desired target genes,thereby reducing possible side effects associated with hitting no n-specific off-target genes,and sign ifica ntly in creasing more efficie ncy as well as higher specificity of in situ gene editi ng in vivo,which holds promise as a powerful,yet feasible tool,to edit disease genes to build corresp on ding huma n disease models in adult NHPs and to greatly accelerate the discovery of new drugs and save economic costs.