Total contents of metals in soil and sediments on the Tibetan Plateau of China have been widely analyzed,but existing information is insufficient to effectively evaluate metal ecological risk because of a lack of meta...Total contents of metals in soil and sediments on the Tibetan Plateau of China have been widely analyzed,but existing information is insufficient to effectively evaluate metal ecological risk because of a lack of metal bioavailability data.In this study,distribution,potential risk,mobility and bioavailability of metals in sediments of Lake Yamdrok Basin in Tibet of China were explored by combined use of total digestion,sequential extraction and the diffusive gradient in thin-films(DGT).Average concentrations of Cr,Ni,Cu,Zn,As,Cd and Pb in surface sediments were 31.25,30.31,22.00,45.04,31.32,0.13 and 13.39 mg/kg,respectively.Higher levels of metals were found near the inflowing rivers.Residual form was dominant in Cr,Ni,Zn,Cd and Pb,and reducible form was dominant in As and Cd.Metals in surface sediments showed a low enrichment degree overall,but Cd and As had higher ecological risk levels than the other metals.Furthermore,there was a larger average proportion of exchangeable form of As(20.4%)and Cd(9.0%)than the other metals(1.7%-3.3%),implying their higher mobility and release risk.Average DGT-labile concentrations of Cr,Ni,Cu,Zn,As,Cd and Pb were 0.5,4.5,0.7,25.1,60.0,0.22 and 1.0μg/L,respectively.The DGT-labile As was significantly correlated with extractable As forms(p<0.01),suggesting that extractable As in sediments acts as a"mobile pool"for bioavailable As.These results suggest potential risks of As and Cd,especially As,deserve further attention in Lake Yamdrok Basin.展开更多
Objective:This study aimed to evaluate the effects of mitochondrial pyruvate carrier(MPC)blockade on the sensitivity of detection and radiotherapy of prostate cancer(PCa).Methods:We investigated glycolysis reprogrammi...Objective:This study aimed to evaluate the effects of mitochondrial pyruvate carrier(MPC)blockade on the sensitivity of detection and radiotherapy of prostate cancer(PCa).Methods:We investigated glycolysis reprogramming and MPC changes in patients with PCa by using metabolic profiling,RNASeq,and tissue microarrays.Transient blockade of pyruvate influx into mitochondria was observed in cellular studies to detect its different effects on prostate carcinoma cells and benign prostate cells.Xenograft mouse models were injected with an MPC inhibitor to evaluate the sensitivity of 18F-fluorodeoxyglucose positron emission tomography with computed tomography and radiotherapy of PCa.Furthermore,the molecular mechanism of this different effect of transient blockage towards benign prostate cells and prostate cancer cells was studied in vitro.Results:MPC was elevated in PCa tissue compared with benign prostate tissue,but decreased during cancer progression.The transient blockade increased PCa cell proliferation while decreasing benign prostate cell proliferation,thus increasing the sensitivity of PCa cells to 18F-PET/CT(SUVavg,P=0.016;SUVmax,P=0.03)and radiotherapy(P<0.01).This differential effect of MPC on PCa and benign prostate cells was dependent on regulation by a VDAC1-MPC-mitochondrial homeostasis-glycolysis pathway.Conclusions:Blockade of pyruvate influx into mitochondria increased glycolysis levels in PCa but not in non-carcinoma prostate tissue.This transient blockage sensitized PCa to both detection and radiotherapy,thus indicating that glycolytic potential is a novel mechanism underlying PCa progression.The change in the mitochondrial pyruvate influx caused by transient MPC blockade provides a critical target for PCa diagnosis and treatment.展开更多
Since androgen receptor(AR)signaling is critically required for the development of prostate cancer(PCa),targeting AR axis has been the standard treatment of choice for advanced and metastatic PCa.Unfortunately,althoug...Since androgen receptor(AR)signaling is critically required for the development of prostate cancer(PCa),targeting AR axis has been the standard treatment of choice for advanced and metastatic PCa.Unfortunately,although the tumor initially responds to the therapy,treatment resistance eventually develops and the disease will progress.It is therefore imperative to identify the mechanisms of therapeutic resistance and novel molecular targets that are independent of AR signaling.Recent advances in pathology,molecular biology,genetics and genomics research have revealed novel AR-independent pathways that contribute to PCa carcinogenesis and progression.They include neuroendocrine differentiation,cell metabolism,DNA damage repair pathways and immune-mediated mechanisms.The development of novel agents targeting the non-AR mechanisms holds great promise to treat PCa that does not respond to AR-targeted therapies.展开更多
Sulfur mustard(SM) can be absorbed by skin quickly and cause serious system damage via reacting with nearly all cell constituents. Until now, there is still lack of effective antidotal therapy for SM and skin protecti...Sulfur mustard(SM) can be absorbed by skin quickly and cause serious system damage via reacting with nearly all cell constituents. Until now, there is still lack of effective antidotal therapy for SM and skin protection is highly important to defend SM. In this article, supramolecular liquid barrier based on pillar[5]arene with triethylene oxide substituents(EGP5) has been designed to impede the skin permeation of SM and further interaction with the skin tissue. EGP5 could encapsulate SM within its cavity, with a Kavalue of(5.10 ± 0.47) × 10^(2)L/mol. In vitro skin absorption test proved that EGP5 was capable to effectively prevent SM from penetrating through skin. This supramolecular liquid barrier was employed on rat models to systematically evaluate protective effect against SM intoxication. Pretreatment of EGP5could alleviate skin and system damage induced by SM and improve survival rate of poisoned rat models from 10% to 90%. Additionally, EGP5 served as protective materials could be highly reused after recycling several times. Overall, these findings have provided the first insight into the construction of convenient liquid material for SM protection.展开更多
Targeted alpha-therapy(TAT) is increasingly attractive due to its extraordinary antitumor efficacy.However,the supply of α-emitters for TAT is insufficient and under control by a limited number of countries.^(212)Pb ...Targeted alpha-therapy(TAT) is increasingly attractive due to its extraordinary antitumor efficacy.However,the supply of α-emitters for TAT is insufficient and under control by a limited number of countries.^(212)Pb is a promising α-emitter with an optimal half-life(10.6 h) and favored decay chain.Of interest,^(212)Pb can be extracted directly from natural thorium,which may be abundant in the mining waste of rare-earth,uranium,etc.Indeed,radioactive thorium waste has been a longstanding environmental challenge that needs immediate action.Developing an on-demand and facile process to isolate ^(212)Pb from natural thorium would be ideal to meet the above challenges,yet is difficult.In theory,the ratio of ^(212)Pb tonatTh is below 10^(-13)in commercially available thorium salts.As a pilot study,2.2 MBq of ^(212)Pb was successfully extracted from a 5 L solution of thorium nitrate by using a Pb-selective resin.The radiochemical purity of ^(212)Pb is over 99.9% according to gamma-ray analysis.The purified^(212)Pb was applied to radiolabel a couple of peptides used in clinics(i.e.PSMA,TATE and FAPI-04),and the radiochemical yields are>85%.Of note,^(212)Pb can be repeatedly separated from the thorium solution every 2 days.In summary,a practical and scalable method was developed to isolate^(212)Pb for potentially clinical use,which may be of great importance as it does not require either cyclotron or nuclear reactor.展开更多
Microvenular hemangioma(MVH)is a rare,benign type of hemangioma that typically presents as a solitary,slow-growing,red-to-violaceous asymptomatic papule,plaque,or nodule.It most commonly locations of the lesions on th...Microvenular hemangioma(MVH)is a rare,benign type of hemangioma that typically presents as a solitary,slow-growing,red-to-violaceous asymptomatic papule,plaque,or nodule.It most commonly locations of the lesions on the limbs and trunk,with no prior reports of MVH confined to the breast.We present the first reported case of multiple MVH confined to the breast in a 17-year-old female patient.The case is notable for its unique and atypical clinical features.Diagnosing MVH is challenging and requires routine pathological and im-munohistochemical staining.Histological testing revealed typical features of MVH,irregularly branched small or medium vascular interstitial spaces lined with benign endothelial cells and positivity for CD34 and CD31.This case emphasizes the need to consider MVH in the dif-ferential diagnosis of breast vascular lesions,particularly in young patients.It also underscores the importance of histological and immu-nohistochemical analyses for an accurate diagnosis.展开更多
Multicharged supramolecular assemblies based on luminescent macrocycle play an important role in extending their optical properties and functions.Herein,we reported macrocyclic supramolecular assemblies based on lumin...Multicharged supramolecular assemblies based on luminescent macrocycle play an important role in extending their optical properties and functions.Herein,we reported macrocyclic supramolecular assemblies based on luminescent terphen[3]arene sulfate(TP[3]AS)and tetraphenylethylene pyridinium(TPE-4Py)through electrostatic interactions,host-vip encapsulation andπ-πstacking interactions.F?rster resonance energy transfer(FRET)process from TP[3]AS to TPE-4Py was achieved with the energy transfer efficiency of 99.9%,accompanied by TPE-4Py fluorescence emission bathochromic shifted of 15 nm and enhanced by 1.68 times in PBS solution.In contrast,other non-luminescent sulfato-β-cyclodextrin and sulfobutylether-β-cyclodextrin only can enhance the fluorescence intensity of TPE-4Py without bathochromic shift.Due to the strong fluorescence and good stability of TPE-4Py@TP[3]AS,it can be used for optical imaging in living cells,which provided an effective approach for the construction of assembling-confined luminescent biomaterials.展开更多
Neuromuscular blocking agents(NMBAs)are extensively used during anesthesia to improve surgical conditions by relaxing skeletal muscle movements.Rapid neuromuscular recovery after surgery is desirable to facilitate the...Neuromuscular blocking agents(NMBAs)are extensively used during anesthesia to improve surgical conditions by relaxing skeletal muscle movements.Rapid neuromuscular recovery after surgery is desirable to facilitate the recovery of muscle function and prevent residual blockade.Decamethonium(C10)is a classic NMBA,which has been restricted over the past decades ascribed to lack of a suitable antidote in clinic.Herein we used carboxylatopillar[6]arene(CP6A)to reverse neuromuscular blocker effect of C10 through direct host-vip encapsulation.NMR and isothermal titration calorimetry served to confirm the complexation between CP6A and C10 with robust affinity[(1.07±0.14)×10^(7)L/mol].The CP6A was further used as a reversal agent of C10,which facilitated to decrease C10 concentration in mice blood and excrete via urinary clearance,resulting in rapid recovery from muscle relaxation.These favorable outcomes might lead us to suggest that this supramolecular strategy could allow patients to regain lucidity much faster than spontaneous recovery from anesthesia.展开更多
Advanced chemotherapy strategies are in urgent demand for improving anticancer efficacy.Herein,a water-soluble pillar[6]arene(WP6 A)was used to load chemotherapeutic agent pemetrexed(PMX)by forming direct host-vip i...Advanced chemotherapy strategies are in urgent demand for improving anticancer efficacy.Herein,a water-soluble pillar[6]arene(WP6 A)was used to load chemotherapeutic agent pemetrexed(PMX)by forming direct host-vip inclusion,which is beneficial for decreasing cytotoxicity of PMX on BEAS-2 B cells.NMR and florescence titration served to confirm the complexation between WP6 A and ATP with higher affinity[(5.67?0.31)x 10^(5)L/mol],favoring competitive replacement of PMX.Complexation ATP by WP6 A effectively prevented ATP from being hydrolyzed in presence of alkaline phosphatase.The formed host-vip complex was further used to block the efflux pump by cutting off energy source from ATP hydrolysis,which was accompanied with releasing PMX to produce synergistic enhancement of anticancer performance towards A549 cells.This supramolecular strategy would also be extended to other clinical chemotherapeutic agents and it was expected to provide salutary profits for cancer patients.展开更多
CONSPECTUS:Macrocycles play pivotal roles in supramolecular chemistry and materials science because of their distinctive molecular recognition capabilities and versatile applications in selfassembly.However,traditiona...CONSPECTUS:Macrocycles play pivotal roles in supramolecular chemistry and materials science because of their distinctive molecular recognition capabilities and versatile applications in selfassembly.However,traditional macrocycles,such as cyclodextrins,calixarenes,cucurbiturils,and pillararenes,have inherent limitations in terms of cavity size and structural variety,which restrict their ability to encapsulate vip molecules of varying sizes and their potential in constructing multifunctional materials.展开更多
Given that chemical warfare agents(CWAs)pose some of the largest threats to humankind,social stability,and world peace,considerable attention has been drawn to the development of the corresponding detection,decontamin...Given that chemical warfare agents(CWAs)pose some of the largest threats to humankind,social stability,and world peace,considerable attention has been drawn to the development of the corresponding detection,decontamination,and treatment techniques.The versatile functionality and distinctive recognition potency of macrocycles enable their customized design for specific tasks,such as chemical sensing,catalysis,or separation.Hence,supramolecular materials are well suited for the establishment of CWA countermeasures.Herein,we summarize the recent progress in the development of macrocycle-based materials for counteracting several representative CWAs,including nerve,blister,blood,incapacitating,choking,and irritating agents,providing a foundation for further advances in this field and fostering practical translational terms.展开更多
While the C_(4)F_(7)N is an environmental-friendly insulation gas with a strong potential to replace SF_(6) in the insulation devices,its decomposed species,especially C_(2)F_(6),C_(3)F_(8),C_(3)F_(6),and CF_(4),exhib...While the C_(4)F_(7)N is an environmental-friendly insulation gas with a strong potential to replace SF_(6) in the insulation devices,its decomposed species,especially C_(2)F_(6),C_(3)F_(8),C_(3)F_(6),and CF_(4),exhibit a strong toxicity and poor insulation performance.In this paper,we propose calcium sulfate(CaSO_(4))as a promising gas adsorbent to scavenge such four toxic species in order to guarantee the safe operation of C_(4)F_(7)N-based insulation devices.Experimental findings show that CaSO_(4) behaves a strong adsorption performance upon the moisture inner the devices and achieves dynamic equilibrium at about 70 h.The adsorption behavior upon four gases is in order of C_(2)F_(6)>CF_(4)>C_(3)F_(8)>C_(3)F_(6) with the adsorbed gas content ranging at 1.5~9 ppm.Theoretical results illustrate that CaSO_(4)(010)surface behaves physisorption upon four toxic gases with Ead ranging at -0.77 to -0.67 eV,and its electronic behavior changes are consistent with the order of QT.Both aspects indicate the strong potential of CaSO_(4) as a promising scavenger for moisture removal,toxic gas sweeping and safe operation of C_(4)F_(7)N-based insulation devices.Our study puts forward a novel adsorbent for toxic gas removal in the gas insulation devices and can stimulate some other cuttingedge researches about adsorbent exploration in this field.展开更多
Fentanyl(Fen)analogs,clinically used anesthetic adjuvants,are often trouble with overdose‐induced adverse effects due torapid entry into the brain plus short retention time.Advanced approaches that can relieve relate...Fentanyl(Fen)analogs,clinically used anesthetic adjuvants,are often trouble with overdose‐induced adverse effects due torapid entry into the brain plus short retention time.Advanced approaches that can relieve related life‐threatening symptomswithout compromising their anesthetic efficacy are urgently needed to satisfy these special requirements.Herein,we proposethat utilization of a well‐matched macrocycle,terphen[3]arene sulfate(TP3S)as a molecular‐level brake for Fen via thepharmacokinetic mode to execute this task.NMR and titration experiments confirm that TP3S possessed strong complexationability toward Fen with an association constant of(1.36±0.12)×10^(6)M^(−1).Then,Transwell assays demonstrate that TP3S itselfis unable to cross the blood–brain barrier,and codosed with Fen could effectively decelerate its velocity of entering the brain.Respiration‐related evaluations and pharmacodynamics analyses reveal that administration of such a brake alleviatesFen‐induced respiratory depression without losing its effectiveness.The therapeutic index of Fen/TP3S is calculated to be~57%higher than that of Fen alone,and through pharmacokinetic studies,it has been clarified that ameliorating Fen's therapeuticoutcome stemmed from reducing the initial brain concentration of Fen and maintaining its effective dose for a longer time.Thissupramolecular approach could also act on other opioids as long as strong binding was achieved.展开更多
Background Sialidosis is an autosomal recessive hereditary disease characterized by the mutation of neuraminidase-1(NEU1)gene,resulting in decreased activity ofα-N-acetylneuraminidase.This leads to metabolic abnormal...Background Sialidosis is an autosomal recessive hereditary disease characterized by the mutation of neuraminidase-1(NEU1)gene,resulting in decreased activity ofα-N-acetylneuraminidase.This leads to metabolic abnormalities in various organs.Sialidosis is classified into two distinct clinical phenotypes,type I and type II,based on the age of onset and severity of clinical manifestations.Case presentation Here,we report a case involving a patient and his two sisters,all of whom showed seizures and ataxia during adolescence,with progressively worsening symptoms.Prior to admission,none of the patients had received a systemic diagnosis or treatment.The whole exome sequencing identified a homozygous NEU1 mutation(NM_000434.3:c.544A>G[p.Ser182Gly])in all three siblings.Their parents and children,who were asymptomatic,were found to be heterozygous carriers.The three patients were ultimately diagnosed with type I sialidosis and treated with antiseizure medications,but they continued to experience recurrent seizures.Conclusions This case report enhances our understanding of sialidosis,particularly in patients presenting with seizures and ataxia.Furthermore,the gene sequencing is a crucial tool for confirming the diagnosis of sialidosis and provides a valuable approach for genetic counseling in affected families.展开更多
Cancer remains a substantial global health challenge,with steadily increasing incidence rates.Radiotherapy(RT)is a crucial component in cancer treatment.Nevertheless,due to limited resources,there is an urgent need to...Cancer remains a substantial global health challenge,with steadily increasing incidence rates.Radiotherapy(RT)is a crucial component in cancer treatment.Nevertheless,due to limited resources,there is an urgent need to enhance both its efficiency and therapeutic efficacy.The integration of Artificial Intelligence(AI)into RT has proven to significantly improve treatment efficiency,especially in time-consuming tasks.This perspective demonstrates how AI enhances the efficiency of target delineation and treatment planning,and introduces the concept of All-in-One RT,which may greatly improve RT efficiency.Furthermore,the concept of Radiotherapy Digital Twins(RDTs)is introduced.By integrating patient-specific data with AI,RDTs enable personalized and precise treatment,as well as the evaluation of therapeutic efficacy.This perspective highlights the transformative impact of AI and digital twin technologies in revolutionizing cancer RT,with the aim of making RT more accessible and effective on a global scale.展开更多
Many recent studies have indicated that cellular communications during plant reproduction, fungal invasion, and defense involve identical or similar molecular players and mechanisms. Indeed, pollen tube invasion and s...Many recent studies have indicated that cellular communications during plant reproduction, fungal invasion, and defense involve identical or similar molecular players and mechanisms. Indeed, pollen tube invasion and sperm release shares many common features with infection of plant tissue by fungi and oomycetes, as a tip-growing intruder needs to communicate with the receptive cells to gain access into a cell and tissue. Depending on the comPatibility between cells, interactions may result in defense, inva- sion, growth support, or cell death. Plant cells stimulated by both pollen tubes and fungal hyphae secrete, for example, small cysteine-rich proteins and receptor-like kinases are activated leading to intracellular signaling events such as the production of reactive oxygen species （ROS） and the generation of calcium （Ca^2＋） transients. The ubiquitous and versatile second messenger Ca^2＋ thereafter plays a central and crucial role in modulating numerous downstream signaling processes. In stimulated cells, it elicits both fast and slow cellular responses depending on the shape, frequency, amplitude, and duration of the Ca^2＋ transients. The various Ca^2＋ signatures are transduced into cellular information via a battery of Ca^2＋-binding proteins. In this review, we focus on Ca^2＋ signaling and discuss its occurrence during plant reproduction and interactions of plant cells with biotrophic filamentous microbes. The participation of Ca^2＋ in ROS signaling pathways is also discussed.展开更多
Trabeculectomy is the mainstay of surgical glaucoma treatment,while the success rate was unsatistying due to postoperative scarring of the filtering blebs.Clinical countermeasures for scar prevention are intraoperativ...Trabeculectomy is the mainstay of surgical glaucoma treatment,while the success rate was unsatistying due to postoperative scarring of the filtering blebs.Clinical countermeasures for scar prevention are intraoperative intervention or repeated subconjunctival injections.Herein,we designed a codelivery system capable of transporting fluorouracil and anti-TGF-β2 oligonucleotide to synergistically inhibit fibroblast proliferation via topical instillation.This co-delivery system was built based on a cationic dendrimer core(PAMAM),which encapsulated fluorouracil within hydrophobic cavity and condensed oligonucleotide with surface amino groups,and was further modified with hyaluronic acid and cell-penetrating peptide penetratin.The co-delivery system was self-assembled into nanoscale complexes with increased cellular uptake and enabled efficient inhibition on proliferation of fibroblast cells.In vivo studies on rabbit trabeculectomy models further confirmed the anti-fibrosis efficiency of the complexes,which prolonged survival time of filtering blebs and maintained their height and extent during wound healing process,exhibiting an equivalent effect on scar prevention compared to intraoperative infiltration with fluorouracil.Qualitative observation by immunohistochemistry staining and quantitative analysis by Western blotting both suggested that TGF-β2 expression was inhibited by the co-delivery complexes.Our study provided a potential approach promising to guarantee success rate of trabeculectomy and prolong survival time of filtering blebs.展开更多
Importance The prevalence and characteristics of short stature(SS)among children in China should be assessed to provide guidance for planning and implementation of nationwide public health policies.Thus far,there have...Importance The prevalence and characteristics of short stature(SS)among children in China should be assessed to provide guidance for planning and implementation of nationwide public health policies.Thus far,there have been no accurate estimates of the prevalence of SS in China.Objective To analyze the prevalence of SS among children in China and to explore the influences of sex,area,age,study year,and study site on prevalence rates.Methods Relevant literature was identified by searching the following databases:PubMed,Embase,The Cochrane Library,Chinese Biomedical Literature,China Knowledge Resource Integrated,WeiPu,and WanFang databases.Meta-analysis was carried out using STATA 11.2.Results This meta-analysis included 39 studies with 348326 Chinese participants;the studies covered 20 provinces,municipalities,and autonomous regions.The pooled prevalence of SS was 3.2%(95%confidence interval[CI],2.6%–3.7%;I2=99.8%).The prevalence of SS in boys and girls were 3.1%(95%CI,2.5%–3.7%)and 3.2%(95%CI,2.6%–3.9%),respectively.The sex difference was not statistically significant(P>0.05).The prevalence of SS was higher in rural areas than in urban areas(4.7%[95%CI,3.6%–5.8%]vs.2.8%[95%CI,2.2%–3.4%];P<0.001).The prevalence of SS was higher in West China(5.2%;95%CI,4.4%–6.0%)than in Northeast China(0.6%;95%CI,0.3%–0.8%),East China(2.3%;95%CI,1.9%–2.8%),or Central China(2.9%;95%CI,1.9%–3.9%).Interpretation The prevalence of SS among children was higher in western and rural areas of China.Close attention to children’s growth and development is needed to prevent the occurrence of SS.展开更多
Purpose–The purpose of this paper is to search for the critical-scenarios of autonomous vehicles(AVs)quickly and comprehensively,which is essential for verification and validation(V&V).Design/methodology/approach...Purpose–The purpose of this paper is to search for the critical-scenarios of autonomous vehicles(AVs)quickly and comprehensively,which is essential for verification and validation(V&V).Design/methodology/approach–The author adopted the index F1 to quantitative critical-scenarios’coverage of the search space and proposed the improved particle swarm optimization(IPSO)to enhance exploration ability for higher coverage.Compared with the particle swarm optimization(PSO),there were three improvements.In the initial phase,the Latin hypercube sampling method was introduced for a uniform distribution of particles.In the iteration phase,the neighborhood operator was adapted to explore more modals with the particles divided into groups.In the convergence phase,the convergence judgment and restart strategy were used to explore the search space by avoiding local convergence.Compared with the Monte Carlo method(MC)and PSO,experiments on the artificial function and critical-scenarios search were carried out to verify the efficiency and the application effect of the method.Findings–Results show that IPSO can search for multimodal critical-scenarios comprehensively,with a stricter threshold and fewer samples in the experiment on critical-scenario search,the coverage of IPSO is 14%higher than PSO and 40%higher than MC.Originality/value–The critical-scenarios’coverage of the search space is firstly quantified by the index F1,and the proposed method has higher search efficiency and coverage for the critical-scenarios search of AVs,which shows application potential for V&V.展开更多
基金supported by the National Natural Science Foundation of China(No.42202018027)。
文摘Total contents of metals in soil and sediments on the Tibetan Plateau of China have been widely analyzed,but existing information is insufficient to effectively evaluate metal ecological risk because of a lack of metal bioavailability data.In this study,distribution,potential risk,mobility and bioavailability of metals in sediments of Lake Yamdrok Basin in Tibet of China were explored by combined use of total digestion,sequential extraction and the diffusive gradient in thin-films(DGT).Average concentrations of Cr,Ni,Cu,Zn,As,Cd and Pb in surface sediments were 31.25,30.31,22.00,45.04,31.32,0.13 and 13.39 mg/kg,respectively.Higher levels of metals were found near the inflowing rivers.Residual form was dominant in Cr,Ni,Zn,Cd and Pb,and reducible form was dominant in As and Cd.Metals in surface sediments showed a low enrichment degree overall,but Cd and As had higher ecological risk levels than the other metals.Furthermore,there was a larger average proportion of exchangeable form of As(20.4%)and Cd(9.0%)than the other metals(1.7%-3.3%),implying their higher mobility and release risk.Average DGT-labile concentrations of Cr,Ni,Cu,Zn,As,Cd and Pb were 0.5,4.5,0.7,25.1,60.0,0.22 and 1.0μg/L,respectively.The DGT-labile As was significantly correlated with extractable As forms(p<0.01),suggesting that extractable As in sediments acts as a"mobile pool"for bioavailable As.These results suggest potential risks of As and Cd,especially As,deserve further attention in Lake Yamdrok Basin.
基金supported by the National Natural Science Foundation of China(NSFC)(Grant No.81902616 to F.W.)Science and Technology Support Project in the field of biomedicine of Shanghai Science and Technology Action Plan(Grant No.19441909200,F.W.)+6 种基金Clinical Research Project of Shanghai Municipal Commission of Health and Family Planning(Grant No.20184Y0130,F.W.)Precision Medicine Program of Second Military Medical University(Grant No.2017JZ35,F.W.)Youth Startup Program of the Second Military Medical University(Grant No.2016QN12,F.W.)Jiangsu Provincial Medical Youth Talent(Grant No.QNRC2016739,X.W.)Shanghai Sailing Program(Grant No.21YF1423300,H.X.)Natural Science Foundation of Shanghai(Grant No.21ZR1437800,H.X.)Cross-disciplinary Research Fund of Shanghai Ninth People’s Hospital,Shanghai Jiaotong University School of Medicine(Grant No.YG2021QN75,H.X.).
文摘Objective:This study aimed to evaluate the effects of mitochondrial pyruvate carrier(MPC)blockade on the sensitivity of detection and radiotherapy of prostate cancer(PCa).Methods:We investigated glycolysis reprogramming and MPC changes in patients with PCa by using metabolic profiling,RNASeq,and tissue microarrays.Transient blockade of pyruvate influx into mitochondria was observed in cellular studies to detect its different effects on prostate carcinoma cells and benign prostate cells.Xenograft mouse models were injected with an MPC inhibitor to evaluate the sensitivity of 18F-fluorodeoxyglucose positron emission tomography with computed tomography and radiotherapy of PCa.Furthermore,the molecular mechanism of this different effect of transient blockage towards benign prostate cells and prostate cancer cells was studied in vitro.Results:MPC was elevated in PCa tissue compared with benign prostate tissue,but decreased during cancer progression.The transient blockade increased PCa cell proliferation while decreasing benign prostate cell proliferation,thus increasing the sensitivity of PCa cells to 18F-PET/CT(SUVavg,P=0.016;SUVmax,P=0.03)and radiotherapy(P<0.01).This differential effect of MPC on PCa and benign prostate cells was dependent on regulation by a VDAC1-MPC-mitochondrial homeostasis-glycolysis pathway.Conclusions:Blockade of pyruvate influx into mitochondria increased glycolysis levels in PCa but not in non-carcinoma prostate tissue.This transient blockage sensitized PCa to both detection and radiotherapy,thus indicating that glycolytic potential is a novel mechanism underlying PCa progression.The change in the mitochondrial pyruvate influx caused by transient MPC blockade provides a critical target for PCa diagnosis and treatment.
基金This work was supported by NIH grant R01 CA172603the National Natural Science Foundation of China(81630019)Youth Culturing Plan of National Natural Science Foundation(2018kj16).
文摘Since androgen receptor(AR)signaling is critically required for the development of prostate cancer(PCa),targeting AR axis has been the standard treatment of choice for advanced and metastatic PCa.Unfortunately,although the tumor initially responds to the therapy,treatment resistance eventually develops and the disease will progress.It is therefore imperative to identify the mechanisms of therapeutic resistance and novel molecular targets that are independent of AR signaling.Recent advances in pathology,molecular biology,genetics and genomics research have revealed novel AR-independent pathways that contribute to PCa carcinogenesis and progression.They include neuroendocrine differentiation,cell metabolism,DNA damage repair pathways and immune-mediated mechanisms.The development of novel agents targeting the non-AR mechanisms holds great promise to treat PCa that does not respond to AR-targeted therapies.
基金financially supported by National Natural Science Foundation of China (Nos. 22171286, 21772118, 21971192)the Natural Science Foundation of Tianjin City (No. 20JCZDJC00200)the Special Fund of Military Medical Science (Nos. BWS16J007,AWS17J009)。
文摘Sulfur mustard(SM) can be absorbed by skin quickly and cause serious system damage via reacting with nearly all cell constituents. Until now, there is still lack of effective antidotal therapy for SM and skin protection is highly important to defend SM. In this article, supramolecular liquid barrier based on pillar[5]arene with triethylene oxide substituents(EGP5) has been designed to impede the skin permeation of SM and further interaction with the skin tissue. EGP5 could encapsulate SM within its cavity, with a Kavalue of(5.10 ± 0.47) × 10^(2)L/mol. In vitro skin absorption test proved that EGP5 was capable to effectively prevent SM from penetrating through skin. This supramolecular liquid barrier was employed on rat models to systematically evaluate protective effect against SM intoxication. Pretreatment of EGP5could alleviate skin and system damage induced by SM and improve survival rate of poisoned rat models from 10% to 90%. Additionally, EGP5 served as protective materials could be highly reused after recycling several times. Overall, these findings have provided the first insight into the construction of convenient liquid material for SM protection.
基金funded by Beijing Municipal Natural Science Foundation (No. Z200018)the Special Foundation of Beijing Municipal Education Commission (No. 3500–12020123)+2 种基金the National Natural Science Foundation of China (Nos. U1867209 and 21778003)the Ministry of Science and Technology of the People’s Republic of China (No. 2017YFA0506300)Li Ge-Zhao Ning Life Science Youth Research Foundation (No. LGZNQN202004)。
文摘Targeted alpha-therapy(TAT) is increasingly attractive due to its extraordinary antitumor efficacy.However,the supply of α-emitters for TAT is insufficient and under control by a limited number of countries.^(212)Pb is a promising α-emitter with an optimal half-life(10.6 h) and favored decay chain.Of interest,^(212)Pb can be extracted directly from natural thorium,which may be abundant in the mining waste of rare-earth,uranium,etc.Indeed,radioactive thorium waste has been a longstanding environmental challenge that needs immediate action.Developing an on-demand and facile process to isolate ^(212)Pb from natural thorium would be ideal to meet the above challenges,yet is difficult.In theory,the ratio of ^(212)Pb tonatTh is below 10^(-13)in commercially available thorium salts.As a pilot study,2.2 MBq of ^(212)Pb was successfully extracted from a 5 L solution of thorium nitrate by using a Pb-selective resin.The radiochemical purity of ^(212)Pb is over 99.9% according to gamma-ray analysis.The purified^(212)Pb was applied to radiolabel a couple of peptides used in clinics(i.e.PSMA,TATE and FAPI-04),and the radiochemical yields are>85%.Of note,^(212)Pb can be repeatedly separated from the thorium solution every 2 days.In summary,a practical and scalable method was developed to isolate^(212)Pb for potentially clinical use,which may be of great importance as it does not require either cyclotron or nuclear reactor.
基金supported by grants from the National Natural Science Foundation of China(no.82104952,no.82004240)Special Project for Clinical Research of Health Industry of Shanghai Municipal Health Commission(no.202140172)+2 种基金Special Project of Medical Innovation Research of Shanghai Science and Technology Commission(no.21Y11923600,no.23Y11921600)Yueyang Hospital of Integrated Traditional Chinese and Western Medicine of Translational Medicine Research Fund(no.2024YYZH05)Young Talents Training Project of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine(no.RY411.07.02.04).
文摘Microvenular hemangioma(MVH)is a rare,benign type of hemangioma that typically presents as a solitary,slow-growing,red-to-violaceous asymptomatic papule,plaque,or nodule.It most commonly locations of the lesions on the limbs and trunk,with no prior reports of MVH confined to the breast.We present the first reported case of multiple MVH confined to the breast in a 17-year-old female patient.The case is notable for its unique and atypical clinical features.Diagnosing MVH is challenging and requires routine pathological and im-munohistochemical staining.Histological testing revealed typical features of MVH,irregularly branched small or medium vascular interstitial spaces lined with benign endothelial cells and positivity for CD34 and CD31.This case emphasizes the need to consider MVH in the dif-ferential diagnosis of breast vascular lesions,particularly in young patients.It also underscores the importance of histological and immu-nohistochemical analyses for an accurate diagnosis.
基金the National Natural Science Foundation of China(Nos.21971192,21807038)the Tianjin Municipal Education Commission(No.2021KJ188)the China Postdoctoral Science Foundation(No.2021T140343)。
文摘Multicharged supramolecular assemblies based on luminescent macrocycle play an important role in extending their optical properties and functions.Herein,we reported macrocyclic supramolecular assemblies based on luminescent terphen[3]arene sulfate(TP[3]AS)and tetraphenylethylene pyridinium(TPE-4Py)through electrostatic interactions,host-vip encapsulation andπ-πstacking interactions.F?rster resonance energy transfer(FRET)process from TP[3]AS to TPE-4Py was achieved with the energy transfer efficiency of 99.9%,accompanied by TPE-4Py fluorescence emission bathochromic shifted of 15 nm and enhanced by 1.68 times in PBS solution.In contrast,other non-luminescent sulfato-β-cyclodextrin and sulfobutylether-β-cyclodextrin only can enhance the fluorescence intensity of TPE-4Py without bathochromic shift.Due to the strong fluorescence and good stability of TPE-4Py@TP[3]AS,it can be used for optical imaging in living cells,which provided an effective approach for the construction of assembling-confined luminescent biomaterials.
基金the Natural Science Foundation of Beijing Municipality(No.7204285)the National Natural Science Foundation of China(Nos.81573354,21772118,21971192)。
文摘Neuromuscular blocking agents(NMBAs)are extensively used during anesthesia to improve surgical conditions by relaxing skeletal muscle movements.Rapid neuromuscular recovery after surgery is desirable to facilitate the recovery of muscle function and prevent residual blockade.Decamethonium(C10)is a classic NMBA,which has been restricted over the past decades ascribed to lack of a suitable antidote in clinic.Herein we used carboxylatopillar[6]arene(CP6A)to reverse neuromuscular blocker effect of C10 through direct host-vip encapsulation.NMR and isothermal titration calorimetry served to confirm the complexation between CP6A and C10 with robust affinity[(1.07±0.14)×10^(7)L/mol].The CP6A was further used as a reversal agent of C10,which facilitated to decrease C10 concentration in mice blood and excrete via urinary clearance,resulting in rapid recovery from muscle relaxation.These favorable outcomes might lead us to suggest that this supramolecular strategy could allow patients to regain lucidity much faster than spontaneous recovery from anesthesia.
基金the National Natural Science Foundation of China(Nos.21772118,21971192,81573354)the Natural Science Foundation of Tianjin City(No.20JCZDJC00200)。
文摘Advanced chemotherapy strategies are in urgent demand for improving anticancer efficacy.Herein,a water-soluble pillar[6]arene(WP6 A)was used to load chemotherapeutic agent pemetrexed(PMX)by forming direct host-vip inclusion,which is beneficial for decreasing cytotoxicity of PMX on BEAS-2 B cells.NMR and florescence titration served to confirm the complexation between WP6 A and ATP with higher affinity[(5.67?0.31)x 10^(5)L/mol],favoring competitive replacement of PMX.Complexation ATP by WP6 A effectively prevented ATP from being hydrolyzed in presence of alkaline phosphatase.The formed host-vip complex was further used to block the efflux pump by cutting off energy source from ATP hydrolysis,which was accompanied with releasing PMX to produce synergistic enhancement of anticancer performance towards A549 cells.This supramolecular strategy would also be extended to other clinical chemotherapeutic agents and it was expected to provide salutary profits for cancer patients.
基金supported by the National Natural Science Foundation of China(22471195,22201212)Natural Science Foundation of Tianjin City(23JCZDJC00660).
文摘CONSPECTUS:Macrocycles play pivotal roles in supramolecular chemistry and materials science because of their distinctive molecular recognition capabilities and versatile applications in selfassembly.However,traditional macrocycles,such as cyclodextrins,calixarenes,cucurbiturils,and pillararenes,have inherent limitations in terms of cavity size and structural variety,which restrict their ability to encapsulate vip molecules of varying sizes and their potential in constructing multifunctional materials.
基金supported by the National Natural Science Foundation of China(22171286 and 22201212)the Natural Science Foundation of Tianjin City(23JCZDJC00660)+1 种基金the Tianjin Municipal Education Commission(2021KJ188)China Postdoctoral Science Foundation(2023M734309)。
文摘Given that chemical warfare agents(CWAs)pose some of the largest threats to humankind,social stability,and world peace,considerable attention has been drawn to the development of the corresponding detection,decontamination,and treatment techniques.The versatile functionality and distinctive recognition potency of macrocycles enable their customized design for specific tasks,such as chemical sensing,catalysis,or separation.Hence,supramolecular materials are well suited for the establishment of CWA countermeasures.Herein,we summarize the recent progress in the development of macrocycle-based materials for counteracting several representative CWAs,including nerve,blister,blood,incapacitating,choking,and irritating agents,providing a foundation for further advances in this field and fostering practical translational terms.
基金supported by National Natural Science Foundation of China(No.51977159).
文摘While the C_(4)F_(7)N is an environmental-friendly insulation gas with a strong potential to replace SF_(6) in the insulation devices,its decomposed species,especially C_(2)F_(6),C_(3)F_(8),C_(3)F_(6),and CF_(4),exhibit a strong toxicity and poor insulation performance.In this paper,we propose calcium sulfate(CaSO_(4))as a promising gas adsorbent to scavenge such four toxic species in order to guarantee the safe operation of C_(4)F_(7)N-based insulation devices.Experimental findings show that CaSO_(4) behaves a strong adsorption performance upon the moisture inner the devices and achieves dynamic equilibrium at about 70 h.The adsorption behavior upon four gases is in order of C_(2)F_(6)>CF_(4)>C_(3)F_(8)>C_(3)F_(6) with the adsorbed gas content ranging at 1.5~9 ppm.Theoretical results illustrate that CaSO_(4)(010)surface behaves physisorption upon four toxic gases with Ead ranging at -0.77 to -0.67 eV,and its electronic behavior changes are consistent with the order of QT.Both aspects indicate the strong potential of CaSO_(4) as a promising scavenger for moisture removal,toxic gas sweeping and safe operation of C_(4)F_(7)N-based insulation devices.Our study puts forward a novel adsorbent for toxic gas removal in the gas insulation devices and can stimulate some other cuttingedge researches about adsorbent exploration in this field.
基金supported by the National Natural Science Foundation of China(22171286 and 22201212).
文摘Fentanyl(Fen)analogs,clinically used anesthetic adjuvants,are often trouble with overdose‐induced adverse effects due torapid entry into the brain plus short retention time.Advanced approaches that can relieve related life‐threatening symptomswithout compromising their anesthetic efficacy are urgently needed to satisfy these special requirements.Herein,we proposethat utilization of a well‐matched macrocycle,terphen[3]arene sulfate(TP3S)as a molecular‐level brake for Fen via thepharmacokinetic mode to execute this task.NMR and titration experiments confirm that TP3S possessed strong complexationability toward Fen with an association constant of(1.36±0.12)×10^(6)M^(−1).Then,Transwell assays demonstrate that TP3S itselfis unable to cross the blood–brain barrier,and codosed with Fen could effectively decelerate its velocity of entering the brain.Respiration‐related evaluations and pharmacodynamics analyses reveal that administration of such a brake alleviatesFen‐induced respiratory depression without losing its effectiveness.The therapeutic index of Fen/TP3S is calculated to be~57%higher than that of Fen alone,and through pharmacokinetic studies,it has been clarified that ameliorating Fen's therapeuticoutcome stemmed from reducing the initial brain concentration of Fen and maintaining its effective dose for a longer time.Thissupramolecular approach could also act on other opioids as long as strong binding was achieved.
基金funded by the Natural Science Foundation of Guangxi(No.2023GXNSFBA026106 and 2024GXNSFAA010107)Guangxi health appropriate technology extension project(S2023017).
文摘Background Sialidosis is an autosomal recessive hereditary disease characterized by the mutation of neuraminidase-1(NEU1)gene,resulting in decreased activity ofα-N-acetylneuraminidase.This leads to metabolic abnormalities in various organs.Sialidosis is classified into two distinct clinical phenotypes,type I and type II,based on the age of onset and severity of clinical manifestations.Case presentation Here,we report a case involving a patient and his two sisters,all of whom showed seizures and ataxia during adolescence,with progressively worsening symptoms.Prior to admission,none of the patients had received a systemic diagnosis or treatment.The whole exome sequencing identified a homozygous NEU1 mutation(NM_000434.3:c.544A>G[p.Ser182Gly])in all three siblings.Their parents and children,who were asymptomatic,were found to be heterozygous carriers.The three patients were ultimately diagnosed with type I sialidosis and treated with antiseizure medications,but they continued to experience recurrent seizures.Conclusions This case report enhances our understanding of sialidosis,particularly in patients presenting with seizures and ataxia.Furthermore,the gene sequencing is a crucial tool for confirming the diagnosis of sialidosis and provides a valuable approach for genetic counseling in affected families.
基金The National Natural Science Foundation of China(grant no.12375334)National Key Research and Development Program of China(grant nos.2023YFC2413200/2023YFC2413201 and 2019YFF01014402)Shenzhen Science and Technology Program,(grant no.KQTD20180411185028798)。
文摘Cancer remains a substantial global health challenge,with steadily increasing incidence rates.Radiotherapy(RT)is a crucial component in cancer treatment.Nevertheless,due to limited resources,there is an urgent need to enhance both its efficiency and therapeutic efficacy.The integration of Artificial Intelligence(AI)into RT has proven to significantly improve treatment efficiency,especially in time-consuming tasks.This perspective demonstrates how AI enhances the efficiency of target delineation and treatment planning,and introduces the concept of All-in-One RT,which may greatly improve RT efficiency.Furthermore,the concept of Radiotherapy Digital Twins(RDTs)is introduced.By integrating patient-specific data with AI,RDTs enable personalized and precise treatment,as well as the evaluation of therapeutic efficacy.This perspective highlights the transformative impact of AI and digital twin technologies in revolutionizing cancer RT,with the aim of making RT more accessible and effective on a global scale.
文摘Many recent studies have indicated that cellular communications during plant reproduction, fungal invasion, and defense involve identical or similar molecular players and mechanisms. Indeed, pollen tube invasion and sperm release shares many common features with infection of plant tissue by fungi and oomycetes, as a tip-growing intruder needs to communicate with the receptive cells to gain access into a cell and tissue. Depending on the comPatibility between cells, interactions may result in defense, inva- sion, growth support, or cell death. Plant cells stimulated by both pollen tubes and fungal hyphae secrete, for example, small cysteine-rich proteins and receptor-like kinases are activated leading to intracellular signaling events such as the production of reactive oxygen species （ROS） and the generation of calcium （Ca^2＋） transients. The ubiquitous and versatile second messenger Ca^2＋ thereafter plays a central and crucial role in modulating numerous downstream signaling processes. In stimulated cells, it elicits both fast and slow cellular responses depending on the shape, frequency, amplitude, and duration of the Ca^2＋ transients. The various Ca^2＋ signatures are transduced into cellular information via a battery of Ca^2＋-binding proteins. In this review, we focus on Ca^2＋ signaling and discuss its occurrence during plant reproduction and interactions of plant cells with biotrophic filamentous microbes. The participation of Ca^2＋ in ROS signaling pathways is also discussed.
基金supported by funding from the National Natural Science Fund of China(Grant Nos.81573358,81172994,81690263 and 81773670)the Development Project of Shanghai Peak Disciplines-Integrative Medicine(20180101,China)
文摘Trabeculectomy is the mainstay of surgical glaucoma treatment,while the success rate was unsatistying due to postoperative scarring of the filtering blebs.Clinical countermeasures for scar prevention are intraoperative intervention or repeated subconjunctival injections.Herein,we designed a codelivery system capable of transporting fluorouracil and anti-TGF-β2 oligonucleotide to synergistically inhibit fibroblast proliferation via topical instillation.This co-delivery system was built based on a cationic dendrimer core(PAMAM),which encapsulated fluorouracil within hydrophobic cavity and condensed oligonucleotide with surface amino groups,and was further modified with hyaluronic acid and cell-penetrating peptide penetratin.The co-delivery system was self-assembled into nanoscale complexes with increased cellular uptake and enabled efficient inhibition on proliferation of fibroblast cells.In vivo studies on rabbit trabeculectomy models further confirmed the anti-fibrosis efficiency of the complexes,which prolonged survival time of filtering blebs and maintained their height and extent during wound healing process,exhibiting an equivalent effect on scar prevention compared to intraoperative infiltration with fluorouracil.Qualitative observation by immunohistochemistry staining and quantitative analysis by Western blotting both suggested that TGF-β2 expression was inhibited by the co-delivery complexes.Our study provided a potential approach promising to guarantee success rate of trabeculectomy and prolong survival time of filtering blebs.
文摘Importance The prevalence and characteristics of short stature(SS)among children in China should be assessed to provide guidance for planning and implementation of nationwide public health policies.Thus far,there have been no accurate estimates of the prevalence of SS in China.Objective To analyze the prevalence of SS among children in China and to explore the influences of sex,area,age,study year,and study site on prevalence rates.Methods Relevant literature was identified by searching the following databases:PubMed,Embase,The Cochrane Library,Chinese Biomedical Literature,China Knowledge Resource Integrated,WeiPu,and WanFang databases.Meta-analysis was carried out using STATA 11.2.Results This meta-analysis included 39 studies with 348326 Chinese participants;the studies covered 20 provinces,municipalities,and autonomous regions.The pooled prevalence of SS was 3.2%(95%confidence interval[CI],2.6%–3.7%;I2=99.8%).The prevalence of SS in boys and girls were 3.1%(95%CI,2.5%–3.7%)and 3.2%(95%CI,2.6%–3.9%),respectively.The sex difference was not statistically significant(P>0.05).The prevalence of SS was higher in rural areas than in urban areas(4.7%[95%CI,3.6%–5.8%]vs.2.8%[95%CI,2.2%–3.4%];P<0.001).The prevalence of SS was higher in West China(5.2%;95%CI,4.4%–6.0%)than in Northeast China(0.6%;95%CI,0.3%–0.8%),East China(2.3%;95%CI,1.9%–2.8%),or Central China(2.9%;95%CI,1.9%–3.9%).Interpretation The prevalence of SS among children was higher in western and rural areas of China.Close attention to children’s growth and development is needed to prevent the occurrence of SS.
基金the National Key Research and Development Program of China.(2021YFB2501205).
文摘Purpose–The purpose of this paper is to search for the critical-scenarios of autonomous vehicles(AVs)quickly and comprehensively,which is essential for verification and validation(V&V).Design/methodology/approach–The author adopted the index F1 to quantitative critical-scenarios’coverage of the search space and proposed the improved particle swarm optimization(IPSO)to enhance exploration ability for higher coverage.Compared with the particle swarm optimization(PSO),there were three improvements.In the initial phase,the Latin hypercube sampling method was introduced for a uniform distribution of particles.In the iteration phase,the neighborhood operator was adapted to explore more modals with the particles divided into groups.In the convergence phase,the convergence judgment and restart strategy were used to explore the search space by avoiding local convergence.Compared with the Monte Carlo method(MC)and PSO,experiments on the artificial function and critical-scenarios search were carried out to verify the efficiency and the application effect of the method.Findings–Results show that IPSO can search for multimodal critical-scenarios comprehensively,with a stricter threshold and fewer samples in the experiment on critical-scenario search,the coverage of IPSO is 14%higher than PSO and 40%higher than MC.Originality/value–The critical-scenarios’coverage of the search space is firstly quantified by the index F1,and the proposed method has higher search efficiency and coverage for the critical-scenarios search of AVs,which shows application potential for V&V.
