Atomically dispersed Ni electrocatalyst for superior urea-assisted water splitting

Urea oxidation reaction(UOR) has been selected as substitution for oxygen evolution reaction ascribing to its low thermodynamic voltage as well as utilization of nickel as electrocatalyst.Herein,we report the formation of nickel single atoms(Ni-SAs) as exceptional bifunctional electrocatalyst toward UOR and hydrogen evolution reaction(HER) in urea-assisted water splitting.In UOR catalysis,Ni-SAs perform a superior catalytic performance than Ni-NP/NC and Pt/C ascribing to the formation of HOO-Ni-N_(4) structure evidenced by in-situ Raman spectroscopy,corresponding to a boosted mass activity by 175-fold at 1.4 V vs.RHE than Ni-NP/NC.Furthermore,Ni-SAs requires only 450 mV overpotential to obtain HER current density of 500 mA cm^(-2).136 mA cm^(-2) is achieved in urea-assisted water splitting at1.7 V for Ni-SAs,boosted by 5.7 times than Pt/C-IrO_(2) driven water splitting.

Antibody-platinum(IV)prodrugs conjugates for targeted treatment of cutaneous squamous cell carcinoma

Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.

Coupling Au with BO_(x) matrix induced by Closo-boron cluster for electrochemical synthesis of ammonia

Au is considered as one of the most promising catalysts for nitrogen reduction reaction(NRR),however maximizing the activity utilization rate of Au and understanding the synergistic effects between Au and carriers pose ongoing challenges.Herein,we systematically explore the synergistic catalytic effect of incorporating Au with boron clusters for accelerating NRR kinetics.An in-situ abinitio strategy is employed to construct B-doped Au nanoparticles(2-6 nm in diameter)loaded on BO_(x) substrates(AuBO_(x)),in which B not only modulates the surface electronic structure of Au but also forms strong coupling interactions to stabilize the nanoparticles.The electrochemical results show that Au-BO_(x) possesses excellent NRR activity(NH_(3) yield of 48.52μg h^(-1)mg_(cat)^(-1),Faraday efficiency of 56.18%),and exhibits high stability and reproducibility throughout the electrocatalytic NRR process.Theoretical calculations reveal that the introduction of B induces the formation of both Au dangling bond and Au-B coupling bond.which considerably facilitates the hydrogenation of~*N_(2)^(-)~*NH_(3).The present work provides a new avenue for the preparation of metal-boron materials achieved by one-step reduction and doping process,utilizing boron clusters as reducing and stabilizing agents.

Nanotechnology assisted photo-and sonodynamic therapy for overcoming drug resistance

Drug resistance is considered the most important reason for the clinical failure of cancer chemotherapy.Circumventing drug resistance and improving the efficacy of anticancer agents remains a major challenge.Over the past several decades,photodynamic therapy(PDT)and sonodynamic therapy(SDT)have attracted substantial attention for their efficacy in cancer treatment,and have been combined with chemotherapy to overcome drug resistance.However,simultaneously delivering sensitizers and chemotherapy drugs to same tumor cell remains challenging,thus greatly limiting this combinational therapy.The rapid development of nanotechnology provides a new approach to solve this problem.Nano-based drug delivery systems can not only improve the targeted delivery of agents but also co-deliver multiple drug components in single nanoparticles to achieve optimal synergistic effects.In this review,we briefly summarize the mechanisms of drug resistance,discuss the advantages and disadvantages of PDT and SDT in reversing drug resistance,and describe state-of-the-art research using nano-mediated PDT and SDT to solve these refractory problems.This review also highlights the clinical translational potential for this combinational therapy.

Gut microbiome profiling and colorectal cancer in African Americans and Caucasian Americans

AIM To determine whether and to what extent the gut microbiome is involved in regulating racial disparity in colorectal cancer(CRC). METHODS All patients were recruited and experiments were performed in accordance with the relevant guidelines and regulations by the Institutional Review Boards (IRB), committees of the John D. Dingell VAMC and Wayne State University guidelines. African American (AA) and Caucasian American (CA) patients were scheduled for an outpatient screening for colonoscopy, and no active malignancy volunteer patients were doubly consented, initially by the gastroenterologist and later by the study coordinator, for participation in the study. The gut microbial communities in colonic effluents from AAs and CAs were examined using 16 sRNA profiling, and bacterial identifications were validated by performing SYBR-based Real Time PCR. For metagenomic analysis to characterize the microbial communities, multiple software/tools were used, including Metastats and R statistical software.RESULTS It is generally accepted that the incidence and mortality of CRC is higher in AAs than in CAs. However, the reason for this disparity is not well understood. We hypothesize that the gut microbiome plays a role in regulating this disparity. Indeed, we found significant differences in species richness and diversity between AAs and CAs. Bacteroidetes was more abundant in AAs than in CAs. In particular, the pro-inflammatory bacteria Fusobacterium nucleatum and Enterobacter species were significantly higher in AAs, whereas probiotic Akkermansia muciniphila and Bifidobacterium were higher in CAs. The polyphyletic Clostridia class showed a divergent pattern, with Clostridium XI elevated in AAs, and Clostridium IV, known for its beneficial function, higher in CAs. Lastly, the AA group had decreased microbial diversity overall in comparison to the CA group. In summary, there were significant differences in pro-inflammatory bacteria and microbial diversity between AA and CA, which may help explain the CRC disparity between groups.CONCLUSION Our current investigation, for the first time, demonstrates microbial dysbiosis between AAs and CAs, which could contribute to the racial disparity of CRC.

Role of cancer stem cells in age-related rise in colorectal cancer

Colorectal cancer(CRC) that comprises about 50% of estimated gastrointestinal cancers remains a high mortality malignancy. It is estimated that CRC will result in 9% of all cancer related deaths. CRC is the third leading malignancy affecting both males and females equally; with 9% of the estimated new cancer cases and 9% cancer related deaths. Sporadic CRC, whose incidence increases markedly with advancing age, occurs in 80%-85% patients diagnosed with CRC. Little is known about the precise biochemical mechanisms responsible for the rise in CRC with aging. However, many probable reasons for this increase have been suggested; among others they include altered carcinogen metabolism and the cumulative effects of long-term exposure to cancer-causing agents. Herein, we propose a role for self-renewing, cancer stem cells(CSCs) in regulating these cellular events. In this editorial, we have briefly described the recent work on the evolution of CSCs in gastro-intestinal track especially in the colon, and how they are involved in the age-related rise in CRC. Focus of this editorial is to provide a description of(1) CSC;(2) epigenetic and genetic mechanisms giving rise to CSCs;(3) markers of CSC;(4) characteristics; and(5) age-related increase in CSC in the colonic crypt.

Racial disparity in colorectal cancer: Gut microbiome and cancer stem cells

Over the past two decades there has been remarkable progress in cancer diagnosis, treatment and screening. The basic mechanisms leading to pathogenesis of various types of cancers are also understood better and some patients, if diagnosed at a particular stage go on to lead a normal pre-diagnosis life. Despite these achievements, racial disparity in some cancers remains a mystery. The higher incidence, aggressiveness and mortality of breast, prostate and colorectal cancers(CRCs) in AfricanAmericans as compared to Caucasian-Americans are now well documented. The polyp-carcinoma sequence in CRC and easy access to colonic epithelia or colonic epithelial cells through colonoscopy/colonic effluent provides the opportunity to study colonic stem cells early in course of natural history of the disease. With the advent of metagenomic sequencing, uncultivable organisms can now be identified in stool and their numbers correlated with the effects on colonic epithelia. It would be expected that these techniques would revolutionize our understanding of the racial disparity in CRC and pave a way for the same in other cancers as well. Unfortunately, this has not happened. Our understanding of the underlying factors responsible in African-Americans for higher incidence and mortality from colorectal carcinoma remains minimal. In this review, we aim to summarize the available data on role of microbiome and cancer stem cells in racial disparity in CRC. This will provide a platform for further research on this topic.

Enhancing near-infrared II photodynamic therapy with nitric oxide for eradicating multidrug-resistant biofilms in deep tissues

Nitric oxide(NO)enhanced photodynamic therapy(PDT)is a promising approach to overcome drug tolerance and resistance to biofilm but is limited by its short excitation wavelengths and low yield of reactive oxygen species(ROS).Herein,we develop a compelling degradable polymer-based near-infrared II(NIR-II,1000-1700 nm)photosensitizer(PNIR-II),which can maintain 50%PDT efficacy even under a 2.6 cm tissue barrier.Remarkably,PNIR-II is synthesized by alternately connecting the electron donor thiophene to the electron acceptors diketopyrrolopyrrole(DPP)and boron dipyrromethene(BODIPY),where the intramolecular charge transfer properties can be tuned to increase the intersystem crossover rate and decrease the internal conversion rate,thereby stabilizing the NIR-II photodynamic rather than photothermal effect.For exerting a combination therapy to eradicate multidrug-resistant biofilms,PNIR-II is further assembled into nanoparticles(NPs)with a synthetic glutathione-triggered NO donor polymer.Under 1064 nm laser radiation,NPs precisely release ROS and NO that triggered by over-expressed GSH in the biofilm microenvironment,thereby forming more bactericidal reactive nitrogen species(RNS)in vitro and in vivo in the mice model that orderly destroy biofilm of multidrug-resistant Staphylococcus aureus cultures from clinical patients.It thus provides a new outlook for destroy the biofilm of deep tissues.

A biomimetic piezoelectric scaffold with sustained Mg^(2+)release promotes neurogenic and angiogenic differentiation for enhanced bone regeneration

Natural bone is a composite tissue made of organic and inorganic components,showing piezoelectricity.Whitlockite(WH),which is a natural magnesium-containing calcium phosphate,has attracted great attention in bone formation recently due to its unique piezoelectric property after sintering treatment and sustained release of magnesium ion(Mg^(2+)).Herein,a composite scaffold(denoted as PWH scaffold)composed of piezoelectric WH(PWH)and poly(ε-caprolactone)(PCL)was 3D printed to meet the physiological demands for the regeneration of neuro-vascularized bone tissue,namely,providing endogenous electric field at the defect site.The sustained release of Mg^(2+)from the PWH scaffold,displaying multiple biological activities,and thus exhibits a strong synergistic effect with the piezoelectricity on inhibiting osteoclast activation,promoting the neurogenic,angiogenic,and osteogenic differentiation of bone marrow mesenchymal stromal cells(BMSCs)in vitro.In a rat calvarial defect model,this PWH scaffold is remarkably conducive to efficient neo-bone formation with rich neurogenic and angiogenic expressions.Overall,this study presents the first example of biomimetic piezoelectric scaffold with sustained Mg^(2+)release for promoting the regeneration of neuro-vascularized bone tissue in vivo,which offers new insights for regenerative medicine.

Self-selective memristor-enabled in-memory search for highly efficient data mining

Similarity search,that is,finding similar items in massive data,is a fundamental computing problem in many fields such as data mining and information retrieval.However,for large-scale and high-dimension data,it suffers from high computational complexity,requiring tremendous computation resources.Here,based on the low-power self-selective memristors,for the first time,we propose an in-memory search(IMS)system with two innovative designs.First,by exploiting the natural distribution law of the devices resistance,a hardware locality sensitive hashing encoder has been designed to transform the realvalued vectors into more efficient binary codes.Second,a compact memristive ternary content addressable memory is developed to calculate the Hamming distances between the binary codes in parallel.Our IMS system demonstrated a 168energy efficiency improvement over all-transistors counterparts in clustering and classification tasks,while achieving a software-comparable accuracy,thus providing a low-complexity and low-power solution for in-memory data mining applications.

Structure-activity relationship of defective electrocatalysts for nitrogen fixation

Ammonia(NH_(3)), as an important chemical substance and clean energy carrier, plays an indispensable role in industrial and agricultural production. The electrocatalytic synthesis of NH+3 under mild conditions has attracted worldwide attention in the energy field due to its environmental friendliness and cost efficiency,but unsatisfactory NH_(3) yields and Faradaic efficiencies are restricting its development. The introduction of defect has been demonstrated as a feasible way to overcome the disadvantages of electrochemistry, as it can regulate the electronic structure and modulate coordination environment of electrocatalysts, which further create active sites and enhance nitrogen adsorption. In this regard, it is necessary to understand the effects of various types of defects on electrocatalysts based on the latest progress in the defect engineering for nitrogen reduction reaction(NRR). In this review, the concept, classifications, and characterization of defects as well as the approaches to create them in electrocatalysts are firstly discussed.Then, certain types of defects(vacancy, dopant, amorphism, edge/corner, and porousness) affecting the performances of various electrocatalysts are further described. Finally, the summary and challenges of electrocatalytic ammonia synthesis are proposed to design advanced electrocatalysts with high efficiency.

Correction to“Spatiotemporally dynamic therapy with shape-adaptive drug-gel for the improvement of tissue regeneration with ordered structure”[Bioact.Mater.8(2022)165-176]

The authors regret that inadvertent errors were observed in Fig.S8.The corrected representative images are now incorporated.This correction does not influence any of the experimental results and discussion or the conclusions reported in the paper.The authors sincerely apologize to the editors and readers for any inconvenience.

Lipid-Based Poly(I:C) Adjuvants Strongly Enhance the Immunogenicity of SARS-CoV-2 Receptor-Binding Domain Vaccine

Background The outbreak of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has greatly threatened public health.Recent studies have revealed that the spike receptor-binding domain(RBD)of SARS-CoV-2 is a potent target for vaccine development.However,adjuvants are usually required to strengthen the immunogenicity of recombinant antigens.Different types of adjuvants can elicit different immune responses.Methods We developed an RBD recombinant protein vaccine with a polyriboinosinic acid–polyribocytidylic acid[poly(I:C)]adjuvant to evoke a strong immune response.The delivery of poly(I:C)was optimized in two steps.First,poly(I:C)was complexed with a cationic polymer,poly-l-lysine(PLL),to form poly(I:C)–PLL,a polyplex core.Thereafter,it was loaded into five different lipid shells(group II,III-1,2-distearoyl-sn-glycero-3-phosphocholine[DSPC],III-1,2-dioleoyl-sn-glycero-3-phosphoethanolamine[DOPE],IV-DOPE,and IV-DSPC).We performed an enzyme-linked immunosorbent assay and enzyme-linked immunosorbent spot assay to compare the ability of the five lipopolyplex adjuvants to enhance the immunogenicity of the SARS-CoV-2 RBD protein,including humoral and cellular immune responses.Finally,the adjuvant with the highest immunogenicity was selected to verify the protective immunity of the vaccine through animal challenge experiments.Results Recombinant RBD protein has low immunogenicity.The different adjuvants we developed enhanced the immunogenicity of the RBD protein in different ways.Among the lipopolyplexes,those containing DOPE(III-DOPE and IV-DOPE)elicited RBD-specific immunoglobulin G antibody responses,and adjuvants with four components elicited better RBD-specific immunoglobulin G antibody responses than those containing three components(P<0.05).The IC50 and IC90 titers indicated that the IV-DOPE lipopolyplex had the greatest neutralization ability,with IC50 titers of 1/117,490.Furthermore,in the challenge study,IV-DOPE lipopolyplex protected mice from SARS-CoV-2 infection.On the fourth day after infection,the average animal body weights were reduced by 18.56%(24.164±0.665 g vs.19.678±0.455 g)and 0.06%(24.249±0.683 g vs.24.235±0.681 g)in the MOCK and vaccine groups,respectively.In addition,the relative expression of viral RNA in the vaccinated group was significantly lower than that in the MOCK group(P<0.05).Interstitial inflammatory cell infiltration was observed in the MOCK group,whereas no obvious damage was observed in the vaccinated group.Conclusions The IV-DOPE–adjuvanted SARS-CoV-2 recombinant RBD protein vaccine efficiently protected mice from SARS-CoV-2 in the animal challenge study.Therefore,IV-DOPE is considered an exceptional adjuvant for SARS-CoV-2 recombinant RBD protein-based vaccines and has the potential to be further developed into a SARS-CoV-2 recombinant RBD protein-based vaccine.

Corrosion mechanism of CuAl-NiC abradable seal coating system——The influence of porosity,multiphase,and multilayer structure on the corrosion failure

In this study,the corrosion behavior of the CuAl-NiC abradable seal coating system in chloride solution was investigated to systematically research the effect of porosity,multiphase,and multilayer structure on the corrosion failure.Through the composition and structure analysis,the corrosion process of the system was predicted and then verified with mercury intrusion porosimetry,cross-section SEM/EDS analysis,and electrochemical measurements.The results demonstrated that the interphase selective corrosion caused the porosity of the top layer to decrease first and then increase during the corrosion development.The interlayer galvanic corrosion,determined by the pore connectivity,is crucial for corrosion failure.

Biosafety chemistry and biosafety materials:A new perspective to solve biosafety problems

Coronavirus disease 2019(COVID‐19)has rapidly swept around the globe since its emergence near 2020.However,people have failed to fully understand its origin or mutation.Defined as an international biosafety incident,COVID‐19 has again encouraged worldwide attention to reconsider the importance of biosafety due to the adverse impact on personal well‐being and social stability.Most countries have already taken measures to advocate progress in biosafety‐relevant research,aiming to prevent and solve biosafety problems with more advanced techniques and products.Herein,we propose a new concept of biosafety chemistry and reiterate the notion of biosafety materials,which refer to the interdisciplinary integration of biosafety and chemistry or materials.We attempt to illustrate the exquisite association that chemistry and materials science possess with biosafety‐science,and we hope to provide a pragmatic perspective on approaches to utilize the knowledge of these two subjects to handle specific biosafety issues,such as detection and disinfection of pathogenic microorganisms,personal protective equipment,vaccine adjuvants and specific drugs,etc..In addition,we hope to promote multidisciplinary cooperation to strengthen biosafety research and facilitate the development of biosafety products to defend national security in the future.

Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration

Exosomes derived from mesenchymal stem cells(MSCs)have demonstrated regenerative potential for cell-free bone tissue engineering,nevertheless,certain challenges,including the confined therapeutic potency of exosomes and ineffective delivery method,are still persisted.Here,we confirmed that hypoxic precondition could induce enhanced secretion of exosomes from stem cells from human exfoliated deciduous teeth(SHEDs)via comprehensive proteomics analysis,and the corresponding hypoxic exosomes(H-Exo)exhibited superior potential in promoting cellular angiogenesis and osteogenesis via the significant up-regulation in focal adhesion,VEGF signaling pathway,and thyroid hormone synthesis.Then,we developed a platform technology enabling the effective delivery of hypoxic exosomes with sustained release kinetics to irregular-shaped bone defects via injection.This platform is based on a simple adsorbing technique,where exosomes are adsorbed onto the surface of injectable porous poly(lactide-co-glycolide)(PLGA)microspheres with bioinspired polydopamine(PDA)coating(PMS-PDA microspheres).The PMS-PDA microspheres could effectively adsorb exosomes,show sustained release of H-Exo for 21 days with high bioactivity,and induce vascularized bone regeneration in 5-mm rat calvarial defect.These findings indicate that the hypoxic precondition and PMS-PDA porous microsphere-based exosome delivery are efficient in inducing tissue regeneration,hence facilitating the clinical translation of exosome-based therapy.

Visible-light-irradiated tandem sulfonylation/cyclization of indole tethered alkenes for the synthesis of tetrahydrocarbazoles

A visible-light-mediated reaction of indole derivatives employing arylsulfonyl chlorides as sulfonyl surrogates has been developed,which proceeds via the sequence of reduction of sulfonyl chloride,sulfonylation,and intramolecular cyclization.This mild protocol transforms a diverse array of indole tethered alkenes and simple sulfonyl chlorides into highly valuable functionalized tetrahydrocarbazoles in good yields.This reaction is also suitable for gram-scale synthesis,which provides an efficient and green access to multi-substituted tetrahydrocarbazoles.

ROS‑Scavenging Electroactive Polyphosphazene‑Based Core–Shell Nanofibers for Bone Regeneration

Bone defects are always accompanied by inflammation due to excessive reactive oxygen species(ROS)in injured regions,which greatly impedes the regeneration of bone tissues.Although many conductive polymers have been developed to scavenge ROS,they are typically non-degradable under physiological conditions,making them unsuitable for in vivo applications.Biodegradable polyorganophosphazenes(POPPs)may serve as potent ROS-scavenging biomaterials owing to their versatile chemical structures and ease of functionalization.Herein,a PATGP-type electroactive polyphosphazene with side groups of aniline tetramer and glycine ethyl ester was compared to conventional poly(lactic-co-glycolic acid)(PLGA)in regenerating bone tissues.To conduct in vitro and in vivo evaluations,three kinds of electrospun nanofibrous meshes were prepared:PLGA,PLGA/PATGP blend,and PLGA/PATGP core–shell nanofibers.Among them,PLGA/PATGP core–shell nanofibers outperform the blend and PLGA nanofibers in terms of scavenging ROS,promoting osteogenic differentiation,and accelerating neo-bone formation.The continuous PATGP shell on the PLGA/PATGP core–shell nanofiber surface could apparently provide more significant modulation effects on cellular behaviors than the PLGA/PATGP blend nanofibers with PATGP dispersed in the PLGA matrix.Therefore,the core–shell structured PLGA/PATGP nanofibers were envisioned as a promising candidate scaffold for bone tissue engineering.Additionally,the core–shell design paved the way for biomedical applications of functional POPPs in combination with other polymeric biomaterials,without phase separation or difficulty of increasing the molecular weights of POPPs.

Fluorine-containing pharmaceuticals approved by the FDA in 2020:Synthesis and biological activity

Thirteen new fluorine-containing drugs,which have been granted approval by the US Food and Drug Administration(FDA)in 2020,are profiled in this review.Therapeutic areas of these new fluorinated pharmaceuticals include medicines and diagnostic agents for Cushing's disease,neurofibromatosis,migraine,Alzheimer's disease,myelodysplastic syndromes,hereditary angioedema attacks,and various cancers.Molecules of these approved drugs feature aromatic fluorine(Ar-F)(11 compounds),aromatic Ar-CF_(3)(1),aliphatic CHF(1)and CF_(2)(1)groups.For each compound,we provide a spectrum of biological activity,medicinal chemistry discovery,and synthetic approaches.

Spatiotemporally dynamic therapy with shape-adaptive drug-gel for the improvement of tissue regeneration with ordered structure

A spatiotemporally dynamic therapy(SDT)is proposed as a powerful therapeutic modality that provides spatially dynamic responses of drug-carriers for adapting to the wound microenvironment.Herein,dynamic chitosan-poly(ethylene glycol)(CP)Schiff-base linkages are employed to perform SDT by directly converting a liquid drug Kangfuxin(KFX)into a gel formation.The obtained KFX-CP drug-gel with shape-adaptive property is used to treat a representative oral mucositis(OM)model in a spatiotemporally dynamic manner.The KFX-CP drug-gel creates an instructive microenvironment to regulate signaling biomolecules and endogenous cells behavior,thereby promoting OM healing by the rule of dynamically adjusting shape to fit the irregular OM regions first,and then provides space for tissue regeneration,over KFX potion control and the general hydrogel group of CP hydrogel and KFX-F127.Most interestingly,the regenerated tissue has ordered structure like healthy tissue.Therefore,the SDT provides a new approach for the design of next generation of wound dressing and tissue engineering materials.