The nature of the deactivation of hydrothermally stable Ni/SiO2–Al2O3 catalyst in long-time aqueous phase hydrogenation of crude 1,4-butanediol

The deactivation of Ni/SiO2-Al2 O3 catalyst in hydrogenation of crude 1,4-butanediol was investigated.During the operation time of 2140 h,the catalyst showed slow activity decay.Characterization results,for four spent catalysts used at different time,indicated that the main reason of the catalyst deactivation was the deposition of carbonaceous species that covered the active Ni and blocked mesopores of the catalyst.The TPO and SEM measurements revealed that the carbonaceous species included both oligomeric and polymeric species with high C/H ratio and showed sheet.Such carbonaceous species might be eliminated through either direct H2 reduction or the combined oxidation-reduction methodologies.

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.

Fusion of EGFP and porcine α 1,3GT genes decrease GFP expression

Objective:To investigate the effect of fusion proteins expressed by the fused gene of porcineα1,3 galactosyltransierase(α1,3 GT) and enhanced green fluorescent protein(EGFP) on the green fluorescence intensity of EGFP.Methods:The fragment containingα1.3GT was firstly recovered after the pcDNA3.1-α1.3GT recombinant vector were digested with BamHl and EcoRI,and then,the resultant fragment was ligated to the pEGFP-N1 vector which was also digested with the same enzymes.The new recombinant eukaryotic expression pEGFP/a 1,3GT vector was obtained and sequenced.The pEGFP/α1,3GT was used to transfect human lung carcinoma cells A549 and HEKC 293FT,and the expression of EGFP was quantitatively analyzed by fluorescent microscope and flow cytometry.Results:The positive percentage of A549 was 80.5%,and that of 293 FT was 86.5%48 hours after the two cell lines both were transfected by pEGFP-N1.The positive percentage of A549 was 75.8%,and that of 293 FT was 81.2%48 hours after the two cell lines were transfected by pEGFP/α1.3GT.The mean fluorescence intensities of A549 transfected with pEGFP-N1 and pEGFP/α1.3GT were 1.21 and 0.956,respectively when compared with that of A549 without transfection.Meanwhile,the those of the 293FT that were transfected with pEGFP-N1 and pEGFP/αl,3GT were 7.66 and 1.00.respectively when compared with that of 293FT cells without transfection.Conclusions:These results suggested that the expression of EGFP gene fused with porcineα1,3GT gene was partly inhibited.

Size Evolution of the Surface Short Fatigue Cracks of 1Cr18Ni9Ti Weld Metal

Size evolution of the surface short fatigue cracks of lCrl8Ni'9Ti weld metal was investigated. A local viewpoint is applied to be agreement with a so-called 'effectively short fatigue crack criterion'. Attention was paid to the dominant effectively short fatigue crack (DESFC) initiation zone and the zones ahead of the DESFC tips. The results revealed that the evolutionary size shows a significant character of microstructural short crack (MSC) and physical short crack (PSC) stages. In the MSC stage, fatigue damage is due to mainly the initiation and irregular growth of the effectively short fatigue cracks (ESFCs). In the PSC stage, the damage is conversely due to mainly the DESFC growth and partially, the growth of the ESFCs and the coalescence of the ESFCs themselves with the DESFC. The process involves from a non-ordered/chaotic state in the initiation of MSC stage, gradually to an independently random state at the transition point between the MSC and PSC stages and then, to an ordered/history-dependent random state. Interactive effect of the collective cracks is stronger and shows an increase in the MSC stage, it reaches a maximum value at the transition point and then, tends to a decrease in the PSC stage. The DESFC acts as a result of the interactive cracks and thus, is deemed suitable to describe the behaviour of collective cracks.

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.

Indoor Radio Propagation Model Based on Dominant Path

When there are bigger obstacles in the indoor environment such as elevator, the radio waves basically can not penetrate it. The contribution of received signal strength by transmission and reflection will be greatly reduced, and most of the time, the radio waves will reach the user by bypass diffraction. Therefore, the traditional path loss model is no longer applicable, and the improved model should be proposed. In this paper, we firstly proposed an indoor radio propagation model based on dominant path in which the received signal strength has nothing to do with the direct distance between user and access point, but is related to the length of dominant path. Then on the basis of dominant path model, the NLOS influence is considered in order to further improve the accuracy of dominant path model. Experimental results demonstrated that the proposed dominant path model can improve the accuracy of traditional path loss model remarkably.

隐睾患儿病因分析及临床诊疗进展

隐睾症(cryptorchidism)也称为睾丸未降,可发生于单侧或双侧,多数位于腹腔到阴囊正常下降路线中的一处(即腹腔、腹股沟管、阴囊上或阴囊高位),异位睾丸也是隐睾症的一种,受多种原因影响异位附着于腹前壁皮下、耻骨部、股部以及对侧腹股沟、阴囊等部位。根据睾丸的位置,可分为可触及睾丸和不可触及睾丸,其中80%的隐睾可触及[1]。目前,隐睾的治疗方式包括内分泌治疗以及外科手术治疗,外科手术治疗包括传统的开放手术和腹腔镜微创手术,但不同位置的隐睾患者最优术式选择仍然是一个争论的问题。需要医务工作者共同面对和解决。随着基础研究和临床研究的进展,学者们对隐睾症有了更深入的了解。本文对近年来隐睾症诊治方面取得的进展进行了综述。

Landscape of global urban environmental resistome and its association with local socioeconomic and medical status

Antimicrobial resistance(AMR)poses a critical threat to global health and development,with environmental factors—particularly in urban areas—contributing significantly to the spread of antibiotic resistance genes(ARGs).However,most research to date has been conducted at a local level,leaving significant gaps in our understanding of the global status of antibiotic resistance in urban environments.To address this issue,we thoroughly analyzed a total of 86,213 ARGs detected within 4,728 metagenome samples,which were collected by the Meta SUB International Consortium involving diverse urban environments in 60 cities of 27 countries,utilizing a deep-learning based methodology.Our findings demonstrated the strong geographical specificity of urban environmental resistome,and their correlation with various local socioeconomic and medical conditions.We also identified distinctive evolutionary patterns of ARG-related biosynthetic gene clusters(BGCs)across different countries,and discovered that the urban environment represents a rich source of novel antibiotics.Our study provides a comprehensive overview of the global urban environmental resistome,and fills a significant gap in our knowledge of large-scale urban antibiotic resistome analysis.

Characteristics of gut microbiota determine effects of specific probiotics strains in patients with functional constipation

To the Editor:Probiotics are a promising treatment modality for functional constipation(FC);however,the factors affecting individual responses to probiotics remain unclear.Growing evidence has identified that there is a strong relationship among the gut microbiota and constipation and related gut-brain axis.[1]The gut microbiota may modulate the gut functions via gut metabolites or trigger the release of gut hormones,such as peptide YY,gastric inhibitory polypeptide,and 5-hydroxytryptamine.[2]In turn,gut hormones affect gut secretion,motility,and sensation through their receptors located on epithelial,enteric,and smooth muscle cells.[2]Based on these findings,exogenous probiotics have been used in patients with constipation;however,few have produced consistent results.[3]In this study,we investigated the efficacy and safety of several specific probiotics strains for constipation,and also examined the potential reasons for the individualized effects of probiotics,which may facilitate interventional decisionmaking for FC patients.

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.

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.

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.

Comparative Studies of Non-noble Metal Modified Mesoporous M-Ni-CaO-ZrO2 （M=Fe, Co, Cu） Catalysts for Simulated Biogas Dry Reforming

The present work is aimed to improve the performance of Ni-based catalysts for biogas dry reforming by adding a second non-noble metal （Fe, Co, Cu） into a previously studied mesoporous Ni-CaO-ZrO2 nanocomposite. Biogas was simulated with equivalent methane and carbon dioxide for the dry reforming reaction. X-ray diffraction （XRD）, X-ray photoelectron spectroscopy （XPS）, N2 adsorption, temperature-programmed reduction （TPR）, thermogravi- metric analysis （TGA）, and transmission electron microscopy （TEM） measurements were taken to characterize the structural and textual properties of the bimetallic catalysts as well as the accumulated carbon deposition. The addition of Fe leads to a less ordering growth of mesopores of Fe-Ni-CaO-ZrO2 sample, and the existence of Cu results in a relatively larger portion of free NiO in Cu-Ni-CaO-ZrO2. Compared with Fe and Cu, the presence of Co could efficiently form a beneficial dual metal effect and enhance the strong metal support interaction between Ni and CaO-ZrO2, thus enhancing the activity and stability of the catalyst in biogas dry reforming reaction.

Review:Development of SARS-CoV-2 immuno-enhanced COVID-19 vaccines with nano-platform

Vaccination is the most effective way to prevent coronavirus disease 2019(COVID-19).Vaccine development approaches consist of viral vector vaccines,DNA vaccine,RNA vaccine,live attenuated virus,and recombinant proteins,which elicit a specific immune response.The use of nanoparticles displaying antigen is one of the alternative approaches to conventional vaccines.This is due to the fact that nano-based vaccines are stable,able to target,form images,and offer an opportunity to enhance the immune responses.The diameters of ultrafine nanoparticles are in the range of 1–100 nm.The application of nanotechnology on vaccine design provides precise fabrication of nanomaterials with desirable properties and ability to eliminate undesirable features.To be successful,nanomaterials must be uptaken into the cell,especially into the target and able to modulate cellular functions at the subcellular levels.The advantages of nano-based vaccines are the ability to protect a cargo such as RNA,DNA,protein,or synthesis substance and have enhanced stability in a broad range of pH,ambient temperatures,and humidity for long-term storage.Moreover,nano-based vaccines can be engineered to overcome biological barriers such as nonspecific distribution in order to elicit functions in antigen presenting cells.In this review,we will summarize on the developing COVID-19 vaccine strategies and how the nanotechnology can enhance antigen presentation and strong immunogenicity using advanced technology in nanocarrier to deliver antigens.The discussion about their safe,effective,and affordable vaccines to immunize against COVID-19 will be highlighted.

Identification of SARS-CoV-2-against aptamer with high neutralization activity by blocking the RBD domain of spike protein 1

Dear Editor,The ongoing outbreak of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)poses a great threat to the public health of people and the normal economic and social development around the world.As of January 8,2021,more than 88 million people were infected with SARS-CoV-2,resulting in more than 1.9 million death.

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.

Significant variations in alternative splicing patterns and expression profiles between human-mouse orthologs in early embryos

Human and mouse orthologs are expected to have similar biological functions; however, many discrepancies have also been reported. We systematically compared human and mouse orthologs in terms of alternative splicing patterns and expression profiles. Human-mouse orthologs are divergent in alternative splicing, as human orthologs could generally encode more isoforms than their mouse orthologs. In early embryos, exon skipping is far more common with human orthologs, whereas constitutive exons are more prevalent with mouse orthologs. This may correlate with divergence in expression of splicing regulators. Orthologous expression similarities are different in distinct embryonic stages, with the highest in morula. Expression differences for orthologous transcription factor genes could play an important role in orthologous expression discordance. We further detected largely orthologous divergence in differential expression between distinct embryonic stages. Collectively, our study uncovers significant orthologous divergence from multiple aspects, which may result in functional differences and dynamics between human-mouse orthologs during embryonic development.

siRNA-functionalized lanthanide nanoparticle enables efficient endosomal escape and cancer treatment

Attaching DNA/RNA to nanomaterials is the basis for nucleic acid-based assembly and drug delivery.Herein,we report that small interfering RNA(siRNA)effectively coordinates with ligand-free lanthanide nanoparticles(NaGdF4 NPs),and forms siRNA/NaGdF4 spherical nucleic acids(SNA).The coordination is primarily attributed to the interaction between Gd and phosphate backbone of the siRNA.Surprisingly,an efficient encapsulation and rapid endosomal escape of siRNA from the endosome/lysosome were achieved,due to its flexible ability to bound to phospholipid head of endosomal membrane,thereby disrupting the membrane structure.Resorting to the dual properties of NaGdF4 NPs,siRNA loading,and endosomal escape,siRNA targeting programmed cell death-ligand 1(siPD-L1)/NaGdF4 SNA triggers significant gene silencing in vitro and in vivo,and effectively represses the tumor growth in both CT26 tumor model and 4T1 orthotopic murine model.

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.