In recent years, perovskite solar cells(PSCs) have propelled into the limelight owing to rapid development of efficiency;however, the abundant defects at the perovskite grain boundaries result in unwanted energy loss ...In recent years, perovskite solar cells(PSCs) have propelled into the limelight owing to rapid development of efficiency;however, the abundant defects at the perovskite grain boundaries result in unwanted energy loss and structural degradation. Here, the grain boundaries of perovskite polycrystalline films have been found to act as nanocapillaries for capturing perovskite quantum dots(PQDs), which enable the conformal assemble of PQDs at the top interspace between perovskite grains. The existence of PQDs passivated the surface defects, optimized the interfacial band alignments, and ultimately improved the power conversion efficiency from 19.27% to 22.47% in inverted PSCs. Our findings open up the possibility of selective assembly and structural modulation of the perovskite nanostructures towards efficient and stable PSCs.展开更多
Background:miRNAs are closely related to bone metabolism.Studies have shown that Erxian decoction can improve bone metabolism,possibly achieving this regulatory effect through miRNA targets.Netinfer was used to predic...Background:miRNAs are closely related to bone metabolism.Studies have shown that Erxian decoction can improve bone metabolism,possibly achieving this regulatory effect through miRNA targets.Netinfer was used to predict the miRNA targets of Erxian decoction for the treatment of postmenopausal osteoporosis,and the results were validated by clinical trials.Methods:In this study,we identified possible targets of Erxian decoction in osteoporosis by means of network pharmacological analysis and bioinformatic prediction.Fifteen cases of postmenopausal osteoporosis with kidney Yin and Yang deficiency(In traditional Chinese medicine,kidney Yin nourishes and moistens the tissues of the internal organs of the body,while kidney Yang promotes and warms the tissues of the internal organs of the body.)were treated with Erxian decoction for four weeks,and serum bone metabolism indices(P1NP,osteocalcin,andβ-CTX)and miRNA-335-5p expression were measured before and after treatment.Results:The constructed miRNA postmenopausal osteoporosis related gene network of the effective compound of the Erxian decoction has 296 points and 981 edges.The 39 postmenopausal osteoporosis related genes regulated by miRNA-335-5p were enriched in ossification,while the signaling pathways were enriched in rheumatoid arthritis,the Toll signaling pathway,the HIF-1 signaling pathway,and the MAPK signaling pathway.After taking Erxian decoction,the expression of the serum bone formation index(P1NP,osteocalcin)and miRNA-335-5p gene expression levels increased significantly.The alterations in P1NP and osteocalcin were correlated with the changes in miRNA-335-5p.Conclusion:Circulating miRNA-335-5p may serve as an important target of Erxian decoction in the treatment of postmenopausal women.The effect of Erxian decoction on bone formation is significant,but the underlying mechanism requires further investigation.展开更多
Chemotherapy-induced complications,particularly lethal cardiovascular diseases,pose significant challenges for cancer survivors.The intertwined adverse effects,brought by cancer and its complication,further complicate...Chemotherapy-induced complications,particularly lethal cardiovascular diseases,pose significant challenges for cancer survivors.The intertwined adverse effects,brought by cancer and its complication,further complicate anticancer therapy and lead to diminished clinical outcomes.Simple supplementation of cardioprotective agents falls short in addressing these challenges.Developing bifunctional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously.Drug repurposing was naturally endowed with co-therapeutic potential of two indications,implying a unique chance in the development of bi-functional agents.Herein,we further proposed a novel“trilogy of drug repurposing”strategy that comprises function-based,targetfocused,and scaffold-driven repurposing approaches,aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent.Through function-based repurposing,a cardioprotective agent,carvedilol(CAR),was identified as a potential neddylation inhibitor to suppress lung cancer growth.Employing target-focused SAR studies and scaffold-driven drug design,we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection.Remarkably,optimal derivative 43 displayed promising bi-functional effects,especially in various self-established heart failure mice models with and without tumor-bearing.Collectively,the present study validated the practicability of the“trilogy of drug repurposing”strategy in the development of bi-functional cotherapy agents.展开更多
Sodium-glucose cotransporter 2(SGLT2)inhibitors have been reapproved for heart failure(HF)therapy in patients with and without diabetes.However,the initial glucose-lowering indication of SGLT2i has impeded their uses ...Sodium-glucose cotransporter 2(SGLT2)inhibitors have been reapproved for heart failure(HF)therapy in patients with and without diabetes.However,the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice.A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect.To address this issue,we conducted structural repurposing of EMPA,a representative SGLT2 inhibitor,to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2.Compared to EMPA,the optimal derivative JX01,which was produced by methylation of C2—OH of the glucose ring,exhibited weaker SGLT2-inhibitory activity(IC_(50)>100 nmol/L),and lower glycosuria and glucose-lowering side-effect,better NHE1-inhibitory activity and cardioprotective effect in HF mice.Furthermore,JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity,and good pharmacokinetic properties in both mouse and rat species.Collectively,the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs,and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.展开更多
Poly(β-peptoid)is a class of polypeptide mimics that possesses excellent biocompatibility and resistance to proteolysis.However,the synthesis of poly(β-peptoid)s with functionalities is a long-standing challenge tha...Poly(β-peptoid)is a class of polypeptide mimics that possesses excellent biocompatibility and resistance to proteolysis.However,the synthesis of poly(β-peptoid)s with functionalities is a long-standing challenge that greatly hinders the functional study and application of poly(β-peptoid)s.We report a controllable and easy synthesis of poly(β-peptoid)s bearing diverse functionalities via the ring-opening polymerization on N-substitutedβ-alanine N-thiocarboxyanhydrides(β-NNTAs).The polymerization can be carried out in openvesselsundermildconditions usingaminesas the initiators to provide poly(β-peptoid)s with targeted molecular weights,narrow dispersities,and diverse functionalities in the side chains and termini.Theβ-NNTAs polymerization is even compatible with initiators bearing unprotected hydroxyl groups.The amphiphilic/cationic poly(β-peptoid)s exhibit a broad spectrum and potent antibacterial activities against multidrug-resistant bacteria.In addition,the highly favored stability ofβ-NNTAmonomers for purification and storage highlights the advantages of thisβ-NNTA polymerization strategy for poly(β-peptoid)s synthesis,functional study,and application as a synthetic mimic of polypeptides.展开更多
We developed a novel Pd-catalyzed[4+4]cycloaddition of(benzo)furan-derived azadienes with homo-TMM all-carbon 1,4-dipoles in situ generated fromα-allyl malonate derivatives,affording an array of benzofuro[3,2-b]azoci...We developed a novel Pd-catalyzed[4+4]cycloaddition of(benzo)furan-derived azadienes with homo-TMM all-carbon 1,4-dipoles in situ generated fromα-allyl malonate derivatives,affording an array of benzofuro[3,2-b]azocines and furo[3,2-b]azocines with good to excellent yields(up to 96%)and exclusive regioselectivities.This methodology featured mild reaction conditions and good functional group tolerance.The synthetic utility was demonstrated by a gram-scale reaction.Furthermore,the catalytic asymmetric[4+4]cycloaddition version has also been explored.展开更多
Diabetic wound is a great threat to patient’s health and lives.The refractory diabetic wound shows spatial inflammation patterns,in which the early-wound pattern depicts a deprived acute inflammatory response,and the...Diabetic wound is a great threat to patient’s health and lives.The refractory diabetic wound shows spatial inflammation patterns,in which the early-wound pattern depicts a deprived acute inflammatory response,and the long-term non-healing wound pattern delineates an excessive and persistent inflammation due to the delayed immune cell infiltration in a positive feedback loop.In this work,we give points to some strategies to normalize the dysregulated immune process based on the spatial inflammation pattern differences in diabetic wound healing.First of all,inhibiting inflammatory response to avoid subsequent persistent and excessive immune infiltration for the early diabetic wound is proposed.However,diabetic wounds are unperceptive trauma that makes patients miss the best treatment time.Therefore,we also introduce two strategies for the long-term non-healing diabetic wound.One strategy is about changing chronic wounds to acute ones,which aims to rejuvenate M1 macrophages in diabetic wounds and make spontaneous M2 polarization possible.To activate the controllable proinflammatory response,western medicine delivers proinflammatory molecules while traditional Chinese medicine develops“wound-pus promoting granulation tissue growth theory”.Another strategy to solve long-term non-healing wounds is seeking switches that target M1/M2 transition directly.These investigations draw a map that delineates strategies for enhancing diabetic wound healing from the perspective of spatial inflammation patterns systematically.展开更多
Nitrogen-vacancy(NV)centers in diamond are progressively favored for room-temperature magnetic field measurement.The signal to noise ratio(SNR)optimization for NV diamond magnetometry generally concentrates on signal ...Nitrogen-vacancy(NV)centers in diamond are progressively favored for room-temperature magnetic field measurement.The signal to noise ratio(SNR)optimization for NV diamond magnetometry generally concentrates on signal amplitude enhancement rather than efficient noise processing.Here,we report a compound filter system combining a wavelet denoising method and an adaptive filter for the realization of an efficient weak magnetic measurement with a high SNR.It allows enhanced magnetic field measurement with an average SNR enhancement of 17.80 dB at 50 nT within 500 mHz to 100 Hz and14.76 dB at 500 mHz within 50 n T to 1100 n T.The introduction of this system in NV diamond magnetometry is aimed to improve signal quality by effectively eliminating the noise and retaining ideal signals.展开更多
Polypeptoids are widely used in biological applications owing to their diverse functions and proteolytic stability.One type of polypeptoids,poly-N-methoxyethylglycine(P-Nmeg),has been found to possess remarkable hydro...Polypeptoids are widely used in biological applications owing to their diverse functions and proteolytic stability.One type of polypeptoids,poly-N-methoxyethylglycine(P-Nmeg),has been found to possess remarkable hydrophilicity and notable properties in terms of protein,cell,and bacterial antifouling.However,the currently known synthesis methods of P-Nmeg include solid-phase synthesis,which is time-consuming and difficult to scale up,and N-substituted N-carboxyanhydride(NNCA)ring-opening polymerization,whose monomers were difficult to store.In this study,we used the chemical stable Nmeg N-phenoxycarbonyl(NPC)as the monomer,which was obtained without the use of highly toxic reactants,such as phosgene or phosphorus halide,to synthesize P-Nmeg under open-vessel conditions.By adding BnNH_(2) as an initiator at 80℃,we can obtain controllable short chain length P-Nmeg with narrow dispersity.展开更多
The presence of protein aggregates in numerous human diseases underscores the significance of detecting these aggregates to comprehend disease mechanisms and develop novel therapeutic approaches for combating these di...The presence of protein aggregates in numerous human diseases underscores the significance of detecting these aggregates to comprehend disease mechanisms and develop novel therapeutic approaches for combating these disorders.Despite the development of various biosensors and fluorescent probes that selectively target amyloid fibers or amorphous aggregates,there is still a lack of tools capable of simultaneously detecting both types of aggregates.Herein,we demonstrate the quantitative discernment of amorphous aggregates by QM-FN-SO3,an aggregationinduced emission(AIE)probe initially designed for detecting amyloid fibers.This probe easily penetrates the membranes of the widely-used prokaryotic model organism Escherichia coli,enabling the visualization of both amorphous aggregates and amyloid fibers through near-infrared fluorescence.Notably,the probe exhibits sensitivity in distinguishing the varying aggregation propensities of proteins,regardless of whether they form amorphous aggregates or amyloid fibers in vivo.These properties contribute to the successful application of the QM-FN-SO3 probe in the subsequent investigation of the antiaggregation activities of two outer membrane protein(OMP)chaperones,both in vitro and in their physiological environment.Overall,our work introduces a near-infrared fluorescent chemical probe that can quantitatively detect amyloid fibers and amorphous aggregates with high sensitivity in vitro and in vivo.Furthermore,it demonstrates the applicability of the probe in chaperone biology and its potential as a high-throughput screening tool for protein aggregation inhibitors and folding factors.展开更多
Wound infections are a compelling health issue caused by the invasion and proliferation of pathogens in wound sites.Antibioticloaded hydrogels are widely used to achieve anti-infectious wound healing.However,due to th...Wound infections are a compelling health issue caused by the invasion and proliferation of pathogens in wound sites.Antibioticloaded hydrogels are widely used to achieve anti-infectious wound healing.However,due to the quick emergence of drugresistant bacteria,such as methicillin-resistant Staphylococcus aureus(MRSA),wound infection has been a formidable challenge to human health.To address MRSA-infected wounds,an antibacterial peptide polymer-loaded hyaluronic acid(HA)hydrogel(Gel-HA@P)is prepared.The peptide polymer is designed to mimic host defense peptides as the antibiotic alternative showing potent antibacterial activity,low susceptibility to drug resistance and good stability against proteolysis.HA is biocompatible and biodegradable hydrogel substrate as a primary constituent of the extracellular matrix and suitable for cell migration and wound healing.Gel-HA@P shows potent activity against MRSA in vitro and in vivo,low toxicity during the treatment and promotes the wound healing in vivo.This design has proven to be an effective and antibiotic-free strategy to enable the healing of MRSA-infected wounds.展开更多
The intensive use of antibiotics intensifies the development of bacterial resistance,which has become a serious problem globally.Methicillin-resistant Staphylococcus aureus(MRSA)has resulted in significant morbidity a...The intensive use of antibiotics intensifies the development of bacterial resistance,which has become a serious problem globally.Methicillin-resistant Staphylococcus aureus(MRSA)has resulted in significant morbidity and mortality.Therefore,it is an urgent need to develop new antimicrobial drugs and administration methods.Herein,we report a dual functional diblock copolymer PLL20-b-PBLG20,which was prepared by superfast and water-insensitive polymerization on N-carboxyanhydrides(NCA)initiated by tetraalkylammonium carboxylate.In addition to direct antimicrobial activity,PLL20-b-PBLG20 also exerts a synergistic bactericidal effect against MRSA with curcumin,a plant extract with antibacterial property.Moreover,PLL20-b-PBLG20 successfully encapsulates curcumin to form nanoparticles via self-assembly.The combination of dual functional PLL20-b-PBLG20 and curcumin holds promise in combating MRSA infections.展开更多
Conjunctival melanoma(CM) is a rare and fatal malignant eye tumor. In this study, we deciphered a novel anti-CM mechanism of a natural tetracyclic compound named as cucurbitacin B(CuB). We found that CuB remarkably in...Conjunctival melanoma(CM) is a rare and fatal malignant eye tumor. In this study, we deciphered a novel anti-CM mechanism of a natural tetracyclic compound named as cucurbitacin B(CuB). We found that CuB remarkably inhibited the proliferation of CM cells including CM-AS16,CRMM1, CRMM2 and CM2005.1, without toxicity to normal cells. CuB can also induce CM cells G2/M cell cycle arrest. RNA-seq screening identified KIF20A, a key downstream effector of FOXM1 pathway, was abolished by CuB treatment. Further target identification by activity-based protein profiling chemoproteomic approach revealed that GRP78 is a potential target of CuB. Several lines of evidence demonstrated that CuB interacted with GRP78 and bound with a Kdvalue of0.11 μmol/L. Furthermore, ATPase activity evaluation showed that CuB suppressed GRP78 both in human recombinant GRP78 protein and cellular lysates. Knockdown of the GRP78 gene significantly induced the downregulation of FOXM1 and related pathway proteins including KIF20A, underlying an interesting therapeutic perspective. Finally, CuB significantly inhibited tumor progression in NCG mice without causing obvious side effects in vivo. Taken together, our current work proved that GRP78-FOXM1-KIF20A as a promising pathway for CM therapy, and the traditional medicine CuB as a candidate drug to hinder this pathway.展开更多
limitation of donor tissue shortage clinically. In addition, suturing-needed transplantation potentially causes postoperative complications. Herein, we design a PEG-Lysozyme injective hydrogel as a suture-free, shape ...limitation of donor tissue shortage clinically. In addition, suturing-needed transplantation potentially causes postoperative complications. Herein, we design a PEG-Lysozyme injective hydrogel as a suture-free, shape self-adaptive, bioactive implant for corneal stroma defect repair. This implant experiences a sol-gel phase transition via an in situ amidation reaction between 4-arm-PEG-NHS and lysozyme. The physicochemical properties of PEG-Lysozyme can be tuned by the components ratio, which confers the implant mimetic corneal modulus and provides tissue adhesion to endure increased intraocular pressure. In vitro tests prove that the implant is beneficial to Human corneal epithelial cells growth and migration due to the bioactivity of lysozyme. Rabbit lamellar keratoplasty experiment demonstrates that the hydrogel can be filled into defect to form a shape-adaptive implant adhered to native stroma. The implant promotes epithelialization and stroma integrity, recovering the topology of injured cornea to normal. A newly established animal forging behavior test prove a rapid visual restoration of rabbits when use implant in a suture free manner. In general, this work provides a promising preclinical practice by applicating a self-curing, shape self-adaptive and bioactive PEG-Lysozyme implant for suture-free stroma repair.展开更多
Chitin oligosaccharides(CHOS),high-value-added oligomers linked by N-acetyl-d-glucosamine(GlcNAc,NAG),and a small amount of d-glucosamine(GlcN,GA),have aroused increasing interest due to their excellent biological pro...Chitin oligosaccharides(CHOS),high-value-added oligomers linked by N-acetyl-d-glucosamine(GlcNAc,NAG),and a small amount of d-glucosamine(GlcN,GA),have aroused increasing interest due to their excellent biological properties,including antibacterial,anti-inflammatory,and immunoprotective activities,and intestinal regulation.The efficient production and utilization of CHOS with high performance can solve problems from chitin as biowaste.However,the large-scale production of well-defined CHOS has not been fully accomplished due to the limited biotechnology and separation methods,thus impeding the research on their biological functions as well as their accurate applications.In this review,we comprehensively summarize the current preparation methods of CHOS,including the chemical,physical,enzymatic and biosynthetic methods.The advantages and disadvantages of the methods are discussed in terms of efficiency,economy,and environmental effects.Furthermore,the applications of CHOS in the food industry and their contributions to human health based on their excellent bioactivities are expounded.It is hoped that this review will help in providing new insights into the production of CHOS with high precision,and support the application of CHOS in serving the food industry as nutritional supplements or foods for special medical purposes.展开更多
Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum...Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.展开更多
The massive use of antibiotics in aquaculture and resulted antibacterial resistance problem urgently need antibiotic substitutions. Herein, we report a promising substitution of aquaculture antibiotics using a synergi...The massive use of antibiotics in aquaculture and resulted antibacterial resistance problem urgently need antibiotic substitutions. Herein, we report a promising substitution of aquaculture antibiotics using a synergistic combination of biodegradable peptide polymers and curcumin, a natural compound from plant. The synergistic combination shows strong antibacterial activity against V. fluvialis and some other common bacteria in aquaculture. The membrane-damaging antibacterial mechanism echoes our finding that the synergistic combination will not induce bacteria to develop resistance after continuous use. The synergistic combination also displays effective cure on V. fluvialis-infected zebrafish. The biodegradability of the peptide polymer enables the combination to lose antibacterial activity and will not cause selective pressure on bacterial in the environment. Our study indicates potential application of synergistic composition, biodegradable peptide polymer and curcumin, as promising antibiotic substitution in aquaculture, which represents a promising strategy to address the global challenge of antimicrobial resistance.展开更多
Automated chemical solid-phase synthesis is an automation platform for rapid and reliable synthesis of glycans.Since the seminal work of Automated Glycan Assembly(AGA)disclosed by Seeberger in 2001,AGA has evolved fro...Automated chemical solid-phase synthesis is an automation platform for rapid and reliable synthesis of glycans.Since the seminal work of Automated Glycan Assembly(AGA)disclosed by Seeberger in 2001,AGA has evolved from a proof-of-concept to a robust and reliable technology for streamlined production of various types of glycans.Through more than 20 years of unceasing efforts,the major breakthroughs in AGA including linkers,approved building blocks,and synthesizers have been acquired,and numerous influential achievements have been made in complex glycan synthesis.In addition,the HPLC-assisted automated synthesis emerges as a promising automation platform to access glycans.In this review,we highlight the key advances in the field of automated chemical solid-phase synthesis,especially in AGA.The synthesis of representative glycans based on AGA is also described.展开更多
Photodynamic(PDT)and photothermal therapies(PTT)are emerging treatments for tumour ablation.Organic dyes such as porphyrin,chlorin,phthalocyanine,boron-dipyrromethene and cyanine are the clinically or preclinically us...Photodynamic(PDT)and photothermal therapies(PTT)are emerging treatments for tumour ablation.Organic dyes such as porphyrin,chlorin,phthalocyanine,boron-dipyrromethene and cyanine are the clinically or preclinically used photosensitizer or photothermal agents.Development of structurally diverse near-infrared dyes with long absorption wavelength is of great significance for PDT and PTT.Herein,we report a novel near-infrared dye ML880 with naphthalimide modified cyanine skeleton.The introduction of naphthalimide moiety results in stronger electron delocalization and larger redshift in emission compared with IR820.Furthermore,ML880 is co-loaded with chemotherapeutic drug into ROS-responsive mesoporous organosilica(RMON)to construct nanomedicine NBD&ML@RMON,which exhibits remarkable tumor inhibition effects through PDT/PTT/chemotherapy in vivo.展开更多
基金financially supported by the National Ten Thousand Talent Program for Young Top-notch Talentthe National Natural Science Fund for Excellent Young Scholars (52022030)+8 种基金the National Natural Science Foundation of China (51972111,52203330)the Shanghai Pilot Program for Basic Research(22TQ1400100-5)the “Dawn” Program of Shanghai Education Commission (22SG28)the Shanghai Municipal Natural Science Foundation (22ZR1418000)the Science and Technology Innovation Plan of Shanghai Science and Technology Commission(22YF1410000)the Postdoctoral Research Foundation of China(2021M701190)the Fundamental Research Funds for the Central Universities (JKM01221621, JKM01221678)the Major Science and Technology Projects of Inner Mongolia Autonomous Region(2021ZD0042)Shanghai Engineering Research Center of Hierarchical Nanomaterials (18DZ2252400)。
文摘In recent years, perovskite solar cells(PSCs) have propelled into the limelight owing to rapid development of efficiency;however, the abundant defects at the perovskite grain boundaries result in unwanted energy loss and structural degradation. Here, the grain boundaries of perovskite polycrystalline films have been found to act as nanocapillaries for capturing perovskite quantum dots(PQDs), which enable the conformal assemble of PQDs at the top interspace between perovskite grains. The existence of PQDs passivated the surface defects, optimized the interfacial band alignments, and ultimately improved the power conversion efficiency from 19.27% to 22.47% in inverted PSCs. Our findings open up the possibility of selective assembly and structural modulation of the perovskite nanostructures towards efficient and stable PSCs.
基金supported by Suzhou Special Project for Diagnosis and Treatment Technology of Clinical Key Diseases(No.LCZX202127)。
文摘Background:miRNAs are closely related to bone metabolism.Studies have shown that Erxian decoction can improve bone metabolism,possibly achieving this regulatory effect through miRNA targets.Netinfer was used to predict the miRNA targets of Erxian decoction for the treatment of postmenopausal osteoporosis,and the results were validated by clinical trials.Methods:In this study,we identified possible targets of Erxian decoction in osteoporosis by means of network pharmacological analysis and bioinformatic prediction.Fifteen cases of postmenopausal osteoporosis with kidney Yin and Yang deficiency(In traditional Chinese medicine,kidney Yin nourishes and moistens the tissues of the internal organs of the body,while kidney Yang promotes and warms the tissues of the internal organs of the body.)were treated with Erxian decoction for four weeks,and serum bone metabolism indices(P1NP,osteocalcin,andβ-CTX)and miRNA-335-5p expression were measured before and after treatment.Results:The constructed miRNA postmenopausal osteoporosis related gene network of the effective compound of the Erxian decoction has 296 points and 981 edges.The 39 postmenopausal osteoporosis related genes regulated by miRNA-335-5p were enriched in ossification,while the signaling pathways were enriched in rheumatoid arthritis,the Toll signaling pathway,the HIF-1 signaling pathway,and the MAPK signaling pathway.After taking Erxian decoction,the expression of the serum bone formation index(P1NP,osteocalcin)and miRNA-335-5p gene expression levels increased significantly.The alterations in P1NP and osteocalcin were correlated with the changes in miRNA-335-5p.Conclusion:Circulating miRNA-335-5p may serve as an important target of Erxian decoction in the treatment of postmenopausal women.The effect of Erxian decoction on bone formation is significant,but the underlying mechanism requires further investigation.
基金supported by the National Natural Science Foundation of China (Grant Nos. 22177076, 81820108022, 22037002)the Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism (2021 Sci&Tech 03-28, China)+4 种基金Shanghai Frontiers Science Center of Disease and Syndrome Biology of Inflammatory Cancer Transformation (2021KJ03-12, China)the Innovative Research Team of High-level Local Universities in Shanghai (SHSMU-ZDCX20212702, China)the Chinese Special Fund for State Key Laboratory of Bioreactor Engineering(2060204)Innovation Program of Shanghai Municipal Education Commission (2019-01-07-00-10-E00056, 2021-01-07-00-02-E00104, China)the Scientific and Technological Innovation Action Plan of Science and Technology Commission of Shanghai(20JC1411300, China)
文摘Chemotherapy-induced complications,particularly lethal cardiovascular diseases,pose significant challenges for cancer survivors.The intertwined adverse effects,brought by cancer and its complication,further complicate anticancer therapy and lead to diminished clinical outcomes.Simple supplementation of cardioprotective agents falls short in addressing these challenges.Developing bifunctional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously.Drug repurposing was naturally endowed with co-therapeutic potential of two indications,implying a unique chance in the development of bi-functional agents.Herein,we further proposed a novel“trilogy of drug repurposing”strategy that comprises function-based,targetfocused,and scaffold-driven repurposing approaches,aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent.Through function-based repurposing,a cardioprotective agent,carvedilol(CAR),was identified as a potential neddylation inhibitor to suppress lung cancer growth.Employing target-focused SAR studies and scaffold-driven drug design,we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection.Remarkably,optimal derivative 43 displayed promising bi-functional effects,especially in various self-established heart failure mice models with and without tumor-bearing.Collectively,the present study validated the practicability of the“trilogy of drug repurposing”strategy in the development of bi-functional cotherapy agents.
基金supported by the National key R&D Program of China(2021YFA0804904)the National Natural Science Foundation of China(22107030)+4 种基金the Chinese Postdoctoral Science Foundation(2020M681211)the Shanghai Morning Light Program(20CG36,China)the Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism(2021 Sci&Tech 03-28,China)the Innovative Research Team of High-level Local Universities in Shanghai(SHSMU-ZDCX20212702,China)the Chinese Special Fund for State Key Laboratory of Bioreactor Engineering(2060204)。
文摘Sodium-glucose cotransporter 2(SGLT2)inhibitors have been reapproved for heart failure(HF)therapy in patients with and without diabetes.However,the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice.A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect.To address this issue,we conducted structural repurposing of EMPA,a representative SGLT2 inhibitor,to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2.Compared to EMPA,the optimal derivative JX01,which was produced by methylation of C2—OH of the glucose ring,exhibited weaker SGLT2-inhibitory activity(IC_(50)>100 nmol/L),and lower glycosuria and glucose-lowering side-effect,better NHE1-inhibitory activity and cardioprotective effect in HF mice.Furthermore,JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity,and good pharmacokinetic properties in both mouse and rat species.Collectively,the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs,and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.
基金supported by the National Natural Science Foundation of China(nos.22075078 and 21861162010)the Free Exploring Basic Research Project at Shenzhen Research Institute of ECUST(no.2021Szvup042)+4 种基金the Program of Shanghai Academic/Technology Research Leader(no.20XD1421400)the National Natural Science Foundation of China for Innovative Research Groups(no.51621002)the China National Postdoctoral Program for Innovative Talents(no.BX2021102)the Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism(Shanghai Municipal Education Commission,grant 2021 Sci&Tech 03-28)the Research Program of the State Key Laboratory of Bioreactor Engineering,the Fundamental Research Funds for the Central Universities(no.JKD01211520).
文摘Poly(β-peptoid)is a class of polypeptide mimics that possesses excellent biocompatibility and resistance to proteolysis.However,the synthesis of poly(β-peptoid)s with functionalities is a long-standing challenge that greatly hinders the functional study and application of poly(β-peptoid)s.We report a controllable and easy synthesis of poly(β-peptoid)s bearing diverse functionalities via the ring-opening polymerization on N-substitutedβ-alanine N-thiocarboxyanhydrides(β-NNTAs).The polymerization can be carried out in openvesselsundermildconditions usingaminesas the initiators to provide poly(β-peptoid)s with targeted molecular weights,narrow dispersities,and diverse functionalities in the side chains and termini.Theβ-NNTAs polymerization is even compatible with initiators bearing unprotected hydroxyl groups.The amphiphilic/cationic poly(β-peptoid)s exhibit a broad spectrum and potent antibacterial activities against multidrug-resistant bacteria.In addition,the highly favored stability ofβ-NNTAmonomers for purification and storage highlights the advantages of thisβ-NNTA polymerization strategy for poly(β-peptoid)s synthesis,functional study,and application as a synthetic mimic of polypeptides.
基金We are grateful for financial support from National Key Research and Development Program of China(2021YFA0804900)the NSFC(22171082,21971062)+1 种基金the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang(No.2022R01007)Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism.
文摘We developed a novel Pd-catalyzed[4+4]cycloaddition of(benzo)furan-derived azadienes with homo-TMM all-carbon 1,4-dipoles in situ generated fromα-allyl malonate derivatives,affording an array of benzofuro[3,2-b]azocines and furo[3,2-b]azocines with good to excellent yields(up to 96%)and exclusive regioselectivities.This methodology featured mild reaction conditions and good functional group tolerance.The synthetic utility was demonstrated by a gram-scale reaction.Furthermore,the catalytic asymmetric[4+4]cycloaddition version has also been explored.
基金Support from the National Natural Science Foundation of China(31922041,11932012,32171341)National key research and development program(2021YFB3800800)+1 种基金the 111 project(B14018)the Science and Technology Innovation Project and Excellent Academic Leader Project of Shanghai Science and Technology Committee(21S31901500,21XD1421100)are acknowledged.
文摘Diabetic wound is a great threat to patient’s health and lives.The refractory diabetic wound shows spatial inflammation patterns,in which the early-wound pattern depicts a deprived acute inflammatory response,and the long-term non-healing wound pattern delineates an excessive and persistent inflammation due to the delayed immune cell infiltration in a positive feedback loop.In this work,we give points to some strategies to normalize the dysregulated immune process based on the spatial inflammation pattern differences in diabetic wound healing.First of all,inhibiting inflammatory response to avoid subsequent persistent and excessive immune infiltration for the early diabetic wound is proposed.However,diabetic wounds are unperceptive trauma that makes patients miss the best treatment time.Therefore,we also introduce two strategies for the long-term non-healing diabetic wound.One strategy is about changing chronic wounds to acute ones,which aims to rejuvenate M1 macrophages in diabetic wounds and make spontaneous M2 polarization possible.To activate the controllable proinflammatory response,western medicine delivers proinflammatory molecules while traditional Chinese medicine develops“wound-pus promoting granulation tissue growth theory”.Another strategy to solve long-term non-healing wounds is seeking switches that target M1/M2 transition directly.These investigations draw a map that delineates strategies for enhancing diabetic wound healing from the perspective of spatial inflammation patterns systematically.
基金supported by the National Natural Science Foundation of China(Nos.61835013,12034007,11874146,12274123)Natural Science Foundation of Shanghai(No.20ZR1414300)。
文摘Nitrogen-vacancy(NV)centers in diamond are progressively favored for room-temperature magnetic field measurement.The signal to noise ratio(SNR)optimization for NV diamond magnetometry generally concentrates on signal amplitude enhancement rather than efficient noise processing.Here,we report a compound filter system combining a wavelet denoising method and an adaptive filter for the realization of an efficient weak magnetic measurement with a high SNR.It allows enhanced magnetic field measurement with an average SNR enhancement of 17.80 dB at 50 nT within 500 mHz to 100 Hz and14.76 dB at 500 mHz within 50 n T to 1100 n T.The introduction of this system in NV diamond magnetometry is aimed to improve signal quality by effectively eliminating the noise and retaining ideal signals.
基金the National Key Research and Development Program of China(No.2022YFC2303100)the National Natural Science Foundation of China(Nos.22075078,22205063)+1 种基金the Shanghai Sailing Program,China(No.22YF1410100)the Fund of the Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism(Shanghai Municipal Education Commission),China.
文摘Polypeptoids are widely used in biological applications owing to their diverse functions and proteolytic stability.One type of polypeptoids,poly-N-methoxyethylglycine(P-Nmeg),has been found to possess remarkable hydrophilicity and notable properties in terms of protein,cell,and bacterial antifouling.However,the currently known synthesis methods of P-Nmeg include solid-phase synthesis,which is time-consuming and difficult to scale up,and N-substituted N-carboxyanhydride(NNCA)ring-opening polymerization,whose monomers were difficult to store.In this study,we used the chemical stable Nmeg N-phenoxycarbonyl(NPC)as the monomer,which was obtained without the use of highly toxic reactants,such as phosgene or phosphorus halide,to synthesize P-Nmeg under open-vessel conditions.By adding BnNH_(2) as an initiator at 80℃,we can obtain controllable short chain length P-Nmeg with narrow dispersity.
基金Natural Science Foundation of Shanghai,Grant/Award Number:23ZR1415300National Natural Science Foundation of China,Grant/Award Numbers:32222049,31661143021,32171269,32201043+1 种基金National Key Research and Development Program of China,Grant/Award Number:2022YFF1102900Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism Shanghai Municipal Education Commission,Grant/Award Number:2021Sci&Tech0328。
文摘The presence of protein aggregates in numerous human diseases underscores the significance of detecting these aggregates to comprehend disease mechanisms and develop novel therapeutic approaches for combating these disorders.Despite the development of various biosensors and fluorescent probes that selectively target amyloid fibers or amorphous aggregates,there is still a lack of tools capable of simultaneously detecting both types of aggregates.Herein,we demonstrate the quantitative discernment of amorphous aggregates by QM-FN-SO3,an aggregationinduced emission(AIE)probe initially designed for detecting amyloid fibers.This probe easily penetrates the membranes of the widely-used prokaryotic model organism Escherichia coli,enabling the visualization of both amorphous aggregates and amyloid fibers through near-infrared fluorescence.Notably,the probe exhibits sensitivity in distinguishing the varying aggregation propensities of proteins,regardless of whether they form amorphous aggregates or amyloid fibers in vivo.These properties contribute to the successful application of the QM-FN-SO3 probe in the subsequent investigation of the antiaggregation activities of two outer membrane protein(OMP)chaperones,both in vitro and in their physiological environment.Overall,our work introduces a near-infrared fluorescent chemical probe that can quantitatively detect amyloid fibers and amorphous aggregates with high sensitivity in vitro and in vivo.Furthermore,it demonstrates the applicability of the probe in chaperone biology and its potential as a high-throughput screening tool for protein aggregation inhibitors and folding factors.
基金supported by the National Natural Science Foundation of China(22075078,52203162)the Program of Shanghai Academic/Technology Research Leader(20XD1421400)+4 种基金Shanghai Sailing Program(21YF1409100)China National Postdoctoral Program for Innovative Talents(BX20220108)the China Postdoctoral Science Foundation(2021M701198)the Open Research Fund of State Key Laboratory of Polymer Physics and Chemistry(Changchun Institute of Applied Chemistry,Chinese Academy of Sciences)the Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism(2021Sci&Tech 03-28,Shanghai Municipal Education Commission)。
文摘Wound infections are a compelling health issue caused by the invasion and proliferation of pathogens in wound sites.Antibioticloaded hydrogels are widely used to achieve anti-infectious wound healing.However,due to the quick emergence of drugresistant bacteria,such as methicillin-resistant Staphylococcus aureus(MRSA),wound infection has been a formidable challenge to human health.To address MRSA-infected wounds,an antibacterial peptide polymer-loaded hyaluronic acid(HA)hydrogel(Gel-HA@P)is prepared.The peptide polymer is designed to mimic host defense peptides as the antibiotic alternative showing potent antibacterial activity,low susceptibility to drug resistance and good stability against proteolysis.HA is biocompatible and biodegradable hydrogel substrate as a primary constituent of the extracellular matrix and suitable for cell migration and wound healing.Gel-HA@P shows potent activity against MRSA in vitro and in vivo,low toxicity during the treatment and promotes the wound healing in vivo.This design has proven to be an effective and antibiotic-free strategy to enable the healing of MRSA-infected wounds.
基金supported by the National Key Research and Development Program of China(2022YFC2303100)the National Natural Science Foundation of China(Nos.52203162,22075078)+5 种基金Program of Shanghai Academic/Technology Research Leader(20xD1421400)China National Postdoctoral Program for Innovative Talents(Bx20220108)the China Postdoctoral Science Foundation(2021M701198)Open Research Fund of State Key Laboratory of Polymer Physics and Chemistry(Changchun Institute of Applied Chemistry,Chinese Academy of Sciences),the Open Project of Engineering Research Center of Dairy Quality and Safety Control Technology(Ministry of Education,R202201)Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism(Shanghai Municipal Education Commission)Research Center of Analysis and Test of East China University of Science and Technology for the help on the characterization in this manuscript.
文摘The intensive use of antibiotics intensifies the development of bacterial resistance,which has become a serious problem globally.Methicillin-resistant Staphylococcus aureus(MRSA)has resulted in significant morbidity and mortality.Therefore,it is an urgent need to develop new antimicrobial drugs and administration methods.Herein,we report a dual functional diblock copolymer PLL20-b-PBLG20,which was prepared by superfast and water-insensitive polymerization on N-carboxyanhydrides(NCA)initiated by tetraalkylammonium carboxylate.In addition to direct antimicrobial activity,PLL20-b-PBLG20 also exerts a synergistic bactericidal effect against MRSA with curcumin,a plant extract with antibacterial property.Moreover,PLL20-b-PBLG20 successfully encapsulates curcumin to form nanoparticles via self-assembly.The combination of dual functional PLL20-b-PBLG20 and curcumin holds promise in combating MRSA infections.
基金supported by the National Mega-project for Innovative Drugs of China(2019ZX09721001-004-003)the National Natural Science Foundation of China(82003603 and 81872747)+1 种基金the Innovative Research Team of High-level Local Universities in Shanghai,the National Special Fund for State Key Laboratory of Bioreactor Engineering(2060204,China)Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism(2021 Sci&Tech 03-28,China).
文摘Conjunctival melanoma(CM) is a rare and fatal malignant eye tumor. In this study, we deciphered a novel anti-CM mechanism of a natural tetracyclic compound named as cucurbitacin B(CuB). We found that CuB remarkably inhibited the proliferation of CM cells including CM-AS16,CRMM1, CRMM2 and CM2005.1, without toxicity to normal cells. CuB can also induce CM cells G2/M cell cycle arrest. RNA-seq screening identified KIF20A, a key downstream effector of FOXM1 pathway, was abolished by CuB treatment. Further target identification by activity-based protein profiling chemoproteomic approach revealed that GRP78 is a potential target of CuB. Several lines of evidence demonstrated that CuB interacted with GRP78 and bound with a Kdvalue of0.11 μmol/L. Furthermore, ATPase activity evaluation showed that CuB suppressed GRP78 both in human recombinant GRP78 protein and cellular lysates. Knockdown of the GRP78 gene significantly induced the downregulation of FOXM1 and related pathway proteins including KIF20A, underlying an interesting therapeutic perspective. Finally, CuB significantly inhibited tumor progression in NCG mice without causing obvious side effects in vivo. Taken together, our current work proved that GRP78-FOXM1-KIF20A as a promising pathway for CM therapy, and the traditional medicine CuB as a candidate drug to hinder this pathway.
基金the National Natural Science Foundation of China(31922041,11932012,32171341)National key research and development program(2021YFB3800800),the 111 project(B14018)+4 种基金the Science and Technology Innovation Project and Excellent Academic Leader Project of Shanghai Science and Technology Committee(21S31901500,21XD1421100)the Scientific and Innovative Action Plan of Shanghai(No.19441900600)the Natural Science Foundation of Shanghai(No.19ZR1408300)the China Postdoctoral Science Foundation(D100-5R-22114)the Shanghai Sailing Program(23YF1409700)are acknowledged.
文摘limitation of donor tissue shortage clinically. In addition, suturing-needed transplantation potentially causes postoperative complications. Herein, we design a PEG-Lysozyme injective hydrogel as a suture-free, shape self-adaptive, bioactive implant for corneal stroma defect repair. This implant experiences a sol-gel phase transition via an in situ amidation reaction between 4-arm-PEG-NHS and lysozyme. The physicochemical properties of PEG-Lysozyme can be tuned by the components ratio, which confers the implant mimetic corneal modulus and provides tissue adhesion to endure increased intraocular pressure. In vitro tests prove that the implant is beneficial to Human corneal epithelial cells growth and migration due to the bioactivity of lysozyme. Rabbit lamellar keratoplasty experiment demonstrates that the hydrogel can be filled into defect to form a shape-adaptive implant adhered to native stroma. The implant promotes epithelialization and stroma integrity, recovering the topology of injured cornea to normal. A newly established animal forging behavior test prove a rapid visual restoration of rabbits when use implant in a suture free manner. In general, this work provides a promising preclinical practice by applicating a self-curing, shape self-adaptive and bioactive PEG-Lysozyme implant for suture-free stroma repair.
基金the National Key R&D Program of China(2019YFD0901805)the 111 Project(B18022),the Fundamental Research Funds for the Central Universities,the Open Project Funding of the State Key Laboratory of Bioreactor Engineering,ECUST(ZDXM2019)Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism(Shanghai Municipal Education Commission).
文摘Chitin oligosaccharides(CHOS),high-value-added oligomers linked by N-acetyl-d-glucosamine(GlcNAc,NAG),and a small amount of d-glucosamine(GlcN,GA),have aroused increasing interest due to their excellent biological properties,including antibacterial,anti-inflammatory,and immunoprotective activities,and intestinal regulation.The efficient production and utilization of CHOS with high performance can solve problems from chitin as biowaste.However,the large-scale production of well-defined CHOS has not been fully accomplished due to the limited biotechnology and separation methods,thus impeding the research on their biological functions as well as their accurate applications.In this review,we comprehensively summarize the current preparation methods of CHOS,including the chemical,physical,enzymatic and biosynthetic methods.The advantages and disadvantages of the methods are discussed in terms of efficiency,economy,and environmental effects.Furthermore,the applications of CHOS in the food industry and their contributions to human health based on their excellent bioactivities are expounded.It is hoped that this review will help in providing new insights into the production of CHOS with high precision,and support the application of CHOS in serving the food industry as nutritional supplements or foods for special medical purposes.
基金supported by the National Natural Science Foundation of China(31730036,31871380,31871382,31930055,31930058,32000500,32022034,32030033,32070730,32130046,3217050247,32150005,32200595,32222024,81730019,81730022,81830014,81921006,81925005,81970426,81971301,81971312,82030041,82061160495,82070805,82071595,82090020,82100841,82120108009,82122024,82125002,82125011,82125012,82130045,82171284,82173061,82173398,82225007,82225015,82225017,82225018,82230047,82230088,82271600,91949106,91949201,92049116,92049302,92049304,92149303,92149306,92157202,92168201,92169102,92249301,92268201)the National Key Research and Development Program of China(2018YFA0800700,2018YFC2000100,2018YFC2000102,2018YFC2002003,2019YFA0110900,2019YFA0801703,2019YFA0801903,2019YFA0802202,2019YFA0904800,2020YFA0113400,2020YFA0803401,2020YFA0804000,2020YFC2002900,2020YFC2008000,2020YFE0202200,2021YFA0804900,2021YFA1100103,2021YFA1100900,2021YFE0114200,2021ZD0202400,2022YFA0806001,2022YFA0806002,2022YFA0806600,2022YFA1103200,2022YFA1103601,2022YFA1103701,2022YFA1103800,2022YFA1103801,2022YFA1104100,2022YFA1104904,2022YFA1303000,2022YFC2009900,2022YFC2502401,2022YFC3602400,2022YFE0118000,2022ZD0213200)+14 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16030302,XDB39000000,XDB39030600)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2020085,2021080)CAS Project for Young Scientists in Basic Research(YSBR-076)the Program of the Beijing Natural Science Foundation(JQ20031)Clinical Research Operating Fund of Central High level hospitals(2022-PUMCHE-001)CAMS Innovation Fund for Medical Sciences(CIFMS)(2022-I2M1-004)Talent Program of the Chinese Academy of Medical Science(2022RC310-10)Research Funds from Health@Inno HK Program launched by Innovation Technology Commission of the Hong Kong Special Administrative Region,Guangdong Basic and Applied Basic Research Foundation(2020B1515020044)Guangzhou Planned Project of Science and Technology(202002020039)the Major Technology Innovation of Hubei Province(2019ACA141)the Science and Technology Major Project of Hunan Provincial Science and Technology Department(2021SK1010)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)the Natural Science Foundation of Sichuan Province(2023NSFSC0003)Yunnan Fundamental Research Project(202201AS070080)the State Key Laboratory of Membrane Biology。
文摘Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.
基金supported by the National Key Research and Development Program of China (2022YFC2303100)the National Natural Science Foundation of China (T2325010, 22305082, 52203162, and 22075078)+6 种基金Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission)the Program of Shanghai Academic/Technology Research Leader (20XD1421400)the Open Research Fund of the State Key Laboratory of Polymer Physics and Chemistry (Changchun Institute of Applied Chemistry, Chinese Academy of Sciences)the Open Project of Engineering Research Center of Dairy Quality and Safety Control Technology (Ministry of Education, R202201)China National Postdoctoral Program for Innovative Talents (BX2021102)China Postdoctoral Science Foundation (2022M710050)the support of the Analysis and Testing Center of School of Chemical Engineering, East China university of Science and Technology。
基金supported by the National Natural Science Foundation of China(Nos.22075078,21861162010)the Program of Shanghai Academic/Technology Research Leader(20XD1421400)+1 种基金Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism(Shanghai Municipal Education Commission)the Fundamental Research Funds for the Central Universities(JKD01211520).
文摘The massive use of antibiotics in aquaculture and resulted antibacterial resistance problem urgently need antibiotic substitutions. Herein, we report a promising substitution of aquaculture antibiotics using a synergistic combination of biodegradable peptide polymers and curcumin, a natural compound from plant. The synergistic combination shows strong antibacterial activity against V. fluvialis and some other common bacteria in aquaculture. The membrane-damaging antibacterial mechanism echoes our finding that the synergistic combination will not induce bacteria to develop resistance after continuous use. The synergistic combination also displays effective cure on V. fluvialis-infected zebrafish. The biodegradability of the peptide polymer enables the combination to lose antibacterial activity and will not cause selective pressure on bacterial in the environment. Our study indicates potential application of synergistic composition, biodegradable peptide polymer and curcumin, as promising antibiotic substitution in aquaculture, which represents a promising strategy to address the global challenge of antimicrobial resistance.
文摘Automated chemical solid-phase synthesis is an automation platform for rapid and reliable synthesis of glycans.Since the seminal work of Automated Glycan Assembly(AGA)disclosed by Seeberger in 2001,AGA has evolved from a proof-of-concept to a robust and reliable technology for streamlined production of various types of glycans.Through more than 20 years of unceasing efforts,the major breakthroughs in AGA including linkers,approved building blocks,and synthesizers have been acquired,and numerous influential achievements have been made in complex glycan synthesis.In addition,the HPLC-assisted automated synthesis emerges as a promising automation platform to access glycans.In this review,we highlight the key advances in the field of automated chemical solid-phase synthesis,especially in AGA.The synthesis of representative glycans based on AGA is also described.
基金supported by National Natural Science Foundation of China(Grants 21878088,12034008,21476077,11727810)Key projects of Shanghai Science and Technology Commission(18DZ1112703)Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism(Shanghai Municipal Education Commission,grant 2021 Sci&Tech 03-28)。
文摘Photodynamic(PDT)and photothermal therapies(PTT)are emerging treatments for tumour ablation.Organic dyes such as porphyrin,chlorin,phthalocyanine,boron-dipyrromethene and cyanine are the clinically or preclinically used photosensitizer or photothermal agents.Development of structurally diverse near-infrared dyes with long absorption wavelength is of great significance for PDT and PTT.Herein,we report a novel near-infrared dye ML880 with naphthalimide modified cyanine skeleton.The introduction of naphthalimide moiety results in stronger electron delocalization and larger redshift in emission compared with IR820.Furthermore,ML880 is co-loaded with chemotherapeutic drug into ROS-responsive mesoporous organosilica(RMON)to construct nanomedicine NBD&ML@RMON,which exhibits remarkable tumor inhibition effects through PDT/PTT/chemotherapy in vivo.
