Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective deli...Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells.To be excited,the development of ionizable drug delivery systems(IDDSs)has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019(COVID-19)in 2021.Compared with conventional cationic gene vectors,IDDSs can decrease the toxicity of carriers to cell membranes,and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures.Despite the progress,there remain necessary requirements for designing more efficient IDDSs for precise gene therapy.Herein,we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms.The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of plasmid DNA(pDNA)and four kinds of RNA.In particular,organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity.We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future,and indicate ideas for developing next generation gene vectors.展开更多
Tailored lipid nanoparticles(LNPs)-mediated small interfering RNA(siRNA)nanomedicines show promise in treating liver disease,such as acute liver injury(ALI)and non-alcoholic steatohepatitis(NASH).However,constructing ...Tailored lipid nanoparticles(LNPs)-mediated small interfering RNA(siRNA)nanomedicines show promise in treating liver disease,such as acute liver injury(ALI)and non-alcoholic steatohepatitis(NASH).However,constructing LNPs that address biosafety concerns,ensure efficient delivery,and target specific hepatic subcellular fractions has been challenging.To evade above obstacles,we develop three novel self-degradable“gemini-like”ionizable lipids(SS-MA,SS-DC,SS-MH)by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head.Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release,improving both biosafety and siRNA delivery efficiency.Furthermore,the distance of ester bond and tertiary amino head significantly influences the LNPs’pKa,thereby affecting endosomal escape,hemolytic efficiency,absorption capacity of ApoE,uptake efficiency of hepatocytes and liver accumulation.We also develop the modified-mannose LNPs(M-LNP)to target liver macrophages specifically.The optimized M-MH_LNP@TNFa exhibits potential in preventing ALI by decreasing tumor necrosis factor a(TNFa)levels in the macrophages,while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2(DGAT2)in the hepatocytes.Our findings provide new insights into developing novel highly effective and low-toxic“gemini-like”ionizable lipids for constructing LNPs,potentially achieving more effective treatment for hepatic diseases.展开更多
Gene therapy using small interfering RNA(siRNA)is emerging as a novel therapeutic approach to treat various diseases.However,safe and efficient siRNA delivery still constitutes the major obstacle for clinical implemen...Gene therapy using small interfering RNA(siRNA)is emerging as a novel therapeutic approach to treat various diseases.However,safe and efficient siRNA delivery still constitutes the major obstacle for clinical implementation of siRNA therapeutics.Here we report an ionizable supramolecular dendrimer vector,formed via self-assembly of a small amphiphilic dendrimer,as an effective siRNA delivery system with a favorable safety profile.By virtue of the ionizable tertiary amine terminals,the supramolecular dendrimer has a low positively charged surface potential and no notable cytotoxicity at physiological pH.Nonetheless,this ionizable feature imparted sufficient surface charge to the supramolecular dendrimer to enable formation of a stable complex with siRNA via electrostatic interactions.The resulting siRNA/dendrimer delivery system had a surface charge that was neither neutral,thus avoiding aggregation,nor too high,thus avoiding cytotoxicity,but was sufficient for favorable cellular uptake and endosomal release of the siRNA.When tested in different cancer cell lines and patient-derived cancer organoids,this dendrimer-mediated siRNA delivery system effectively silenced the oncogenes Myc and Akt2 with a potent antiproliferative effect,outperforming the gold standard vector,Lipofectamine 2000.Therefore,this ionizable supramolecular dendrimer represents a promising vector for siRNA delivery.The concept of supramolecular dendrimer nanovectors via self-assembly is new,yet easy to implement in practice,offering a new perspective for supramolecular chemistry in biomedical applications.展开更多
The electrochemical behavior of ionizable drugs (Amitriptyline, Diphenhydramine and Trihexyphene- dyl) at the water/1,2-dichloroethane interface with the phase volume ratio (r = Vo/Vw) equal to 1 are investigated by c...The electrochemical behavior of ionizable drugs (Amitriptyline, Diphenhydramine and Trihexyphene- dyl) at the water/1,2-dichloroethane interface with the phase volume ratio (r = Vo/Vw) equal to 1 are investigated by cyclic voltammetry. The system is composed of an aqueous droplet supported at an Ag/AgCl disk electrode and it was covered with an organic solution. In this manner, a conventional three-electrode potentiostat can be used to study the ioni-zable drugs transfer process at a liquid/liquid interface. Physicochemical parameters such as the formal transfer potential, the Gibbs energy of transfer and the standard par-tition coefficients of the ionized forms of these drugs can be evaluated from cyclic voltammograms obtained. The ob-tained results have been summarized in ionic partition dia-grams, which are a useful tool for predicting and interpret-ing the transfer mechanisms of ionizable drugs at the liq-uid/liquid interfaces and biological membranes.展开更多
The migration mechanism of ionizable compounds in capillary electrochromatography (CEC) is more complicated than in high performance liquid chromatography (HPLC) due to the involvement of electrophoresis and the secon...The migration mechanism of ionizable compounds in capillary electrochromatography (CEC) is more complicated than in high performance liquid chromatography (HPLC) due to the involvement of electrophoresis and the second chemical equilibrium. The separation mechanism of ionizable compounds in CEC has been studied theoretically. The electrochromatographic capacity factors of ions ( k * ) in CEC and in the pressurized CEC are derived by phenomenologi-cal approach. The influence of pH, voltage, pressure on k * is discussed. In addition, the k * of weak acid and weak base are derived based on acid-base equilibrium and the influence of pH on k is studied theoretically.展开更多
Messenger ribonucleic acid(mRNA)-based therapeutics hold great prospects in disease treatment and lipid nanoparticles(LNPs)are the most extensively applied non-viral platform for RNA delivery in clinics.Despite the cl...Messenger ribonucleic acid(mRNA)-based therapeutics hold great prospects in disease treatment and lipid nanoparticles(LNPs)are the most extensively applied non-viral platform for RNA delivery in clinics.Despite the clinical success of LNPs as vehicles have been achieved,developing LNPs with enhanced mRNA transmembrane delivery and transfection efficiency in a non-toxic manner is highly desirable and challenging.In this study,we designed a series of new ionizable amino lipids with piperazinederived headgroups and constructed a group of LNPs to promote the transfection activity of mRNA cargos.Among them,LNP formulated with lipid 10(L10-LNP)can efficiently package mRNA and perform superior transfection efficiency both in vitro and in vivo,which is mainly attributed to the improved intracellular uptake and effective endosomal escape.We verified that a single administration of L10-LNP packaging interleukin(IL)-12 mRNA induced tumor shrink and even regression by robust activation of immune effector CD8^(+)T cells and stimulating the generation of IFN-γwithout causing systemic toxicity,which provides a promising platform for clinical cancer immunotherapy.展开更多
Abiotic oxygen formation predates photosynthesis,sustaining early chemical evolution,yet its elementary mechanisms remain contested.Here,we show the production pathways for molecular oxygen from doubly ionized carbon ...Abiotic oxygen formation predates photosynthesis,sustaining early chemical evolution,yet its elementary mechanisms remain contested.Here,we show the production pathways for molecular oxygen from doubly ionized carbon dioxide upon electron-impact.Through fragment ions and electron coincidence momentum imaging,we unambiguously determine the ionization mechanism by measuring the projectile energy loss in association with the C^(+) +O_(2)^(+) channel.Further potential energy and trajectory calculations enable us to elucidate the dynamical details of this fragmentation process,in which a bond rearrangement pathway is found to proceed via the structural deformation to a triangular intermediate.Moreover,we demonstrate a further roaming pathway for the formation of O_(2)^(+) from CO_(2)^(+) 2,in which a frustrated C-O bond cleavage leaves the O atom without sufficient energy to escape.The O atom then wanders around varied configuration spaces of the flat potential energy regions and forms a C-O-O_(2)^(+) intermediate prior to the final products C^(+) +O_(2)^(+).Considering the large quantities of free electrons in interstellar space,the processes revealed here are expected to be significant and should be incorporated into atmospheric evolution models.展开更多
This study focuses on a 60 V trench MOSFET device designed for operation in space radiation environments.By increasing the bulk region concentration and placing the etched gate trench after the P+implantation process,...This study focuses on a 60 V trench MOSFET device designed for operation in space radiation environments.By increasing the bulk region concentration and placing the etched gate trench after the P+implantation process,we successfully reduced the threshold voltage shift from 6.5 to 2.2 V under a total dose of 400 krad(Si)^(60)Co,allowing the device to operate normally.Structurally,by embedding the source metal in the active and terminal regions,the device demonstrated current degradation without experiencing single-event burnout when subjected to a drain voltage of 60 V and a linear energy transfer value of 75.4 MeV·cm^(2)∕mg from tantalum-ion incidence.TCAD simulations verified that the embedded source metal effectively suppressed parasitic transistor conduction and eliminated the base-region expansion effect,thereby lowering the maximum temperature from 8000 to 1400 K.The irradiation effects of the embedded source metal in the terminal region were also investigated,which can improve the reverse recovery and ensure that the terminal metal does not melt prematurely,thereby significantly enhancing the radiation hardness of the device.展开更多
The efficient and sustainable removal of refractory high ionization potential(high-IP)organic pollutants remains challenging due to their redox inertness and poor interfacial electron transfer.Herein,we report a suspe...The efficient and sustainable removal of refractory high ionization potential(high-IP)organic pollutants remains challenging due to their redox inertness and poor interfacial electron transfer.Herein,we report a suspended photo-Fenton membrane (2D-C_(3)N_(4)/Fe-N-C/GO) that circumvents these limitations via a self-sufficient oxidant generation pathway,enabling low-carbon abatement of high-IP pollutants.This multifunctional architecture couples the visible-light-driven production of hydrogen peroxide(H_(2)O_(2)) by two-dimensional carbon nitride(2D-C_(3)N_(4)) with the Fe-N-C mediated adsorption and activation of electron-deficient species via pyridinic N-Fe^(2+)/Fe^(3+) redox pairs.Under light irradiation,photogenerated electrons continuously regenerate Fe^(2+) from Fe^(3+),sustaining reactive oxygen species(·OH)production and promoting efficient oxidative mineralization.The system demonstrates robust long-term performance in both synthetic and real wastewater matrices,achieving superior degradation and chemical oxygen demand(COD)removal.Life cycle assessment(LCA)confirms its environmental superiority over conventional homogeneous Fenton processes,with markedly reduced carbon emissions and ecological impacts.This work offers a mechanistically insightful and practically viable platform for the green,efficient,and durable remediation of high-IP organic pollutants,providing conceptual guidance for next-generation catalytic wastewater treatment technologies.展开更多
This article introduces a novel 20 V radiation-hardened high-voltage metal-oxide-semiconductor field-effect transistor(MOSFET)driver with an optimized input circuit and a drain-surrounding-source(DSS)structure.The inp...This article introduces a novel 20 V radiation-hardened high-voltage metal-oxide-semiconductor field-effect transistor(MOSFET)driver with an optimized input circuit and a drain-surrounding-source(DSS)structure.The input circuit of a conventional inverter consists of a thick-gate-oxide n-type MOSFET(NMOS).These conventional drivers can tolerate a total ionizing dose(TID)of up to 100 krad(Si).In contrast,the proposed comparator input circuit uses both a thick-gate-oxide p-type MOSFET(PMOS)and thin-gate-oxide NMOS to offer a high input voltage and higher TID tolerance.Because the thick-gate-oxide PMOS and thin-gate-oxide NMOS collectively provide better TID tolerance than the thick-gate-oxide NMOS,the circuit exhibits enhanced TID tolerance of>300 krad(Si).Simulations and experimental date indicate that the DSS structure reduces the probability of unwanted parasitic bipolar junction transistor activation,yielding a better single-event effect tolerance of over 81.8 MeVcm^(2)mg^(-1).The innovative strategy proposed in this study involves circuit and layout design optimization,and does not require any specialized process flow.Hence,the proposed circuit can be manufactured using common commercial 0.35μm BCD processes.展开更多
Formic and acetic acids are the most abundant gaseous organic acids and play the key role in the atmospheric chemistry.In iodine-adduct chemical ionizationmass spectrometry(CIMS),the low utilization efficiency of meth...Formic and acetic acids are the most abundant gaseous organic acids and play the key role in the atmospheric chemistry.In iodine-adduct chemical ionizationmass spectrometry(CIMS),the low utilization efficiency of methyl iodide and humidity interference are two major issues of the vacuum ultraviolet(VUV)lamp initiated CIMS for on-line gaseous formic and acetic acids analysis.In this work,we present a new CIMS based on VUV lamp,and the ion-molecular reactor is separated into photoionization and chemical ionization zones by a reducer electrode.Acetone was added to the photoionization zone,and the VUV photoionization acetone provided low-energy electrons for methyl iodide to generate I−,and the addition of acetone reduced the amount of methyl iodide by 2/3.In the chemical ionization zone,a headspace vial containing ultrapure water was added for humidity calibration,and the vial changes the sensitivity as a function of humidity from ambiguity to well linear correlation(R2>0.95).With humidity calibration,the CIMS can quantitatively measure formic and acetic acids in the humidity range of 0%-88%RH.In this mode,limits of detection of 10 and 50 pptv are obtained for formic and acetic acids,respectively.And the relative standard deviation(RSD)of quantitation stability for 6 days were less than 10.5%.This CIMS was successfully used to determine the formic and acetic acids in the underground parking and ambient environment of the Shandong University campus(Qingdao,China).In addition,we developed a simple model based formic acid concentration to assess vehicular emissions.展开更多
Accidental exposure to overdose ionizing radiation will inevitably lead to severe biological damage,thus detecting and localizing radiation is essential.Traditional measurement techniques are generally restricted to t...Accidental exposure to overdose ionizing radiation will inevitably lead to severe biological damage,thus detecting and localizing radiation is essential.Traditional measurement techniques are generally restricted to the detection range of few centimeters,posing a great risk to operators.The prospect in remote sensing makes femtosecond laser filament technology a great candidate for constructively addressing this challenge.Here we propose a novel filament-based ionizing radiation sensing method,and clarify the interaction mechanism between filaments and ionizing radiation from systematic experiment to microscopic theory.Specifically,it is demonstrated that the energetic electrons produced byαradiation in air can be effectively accelerated within the filament,serving as seed electrons,which will enhance nitrogen fluorescence.The extended nitrogen fluorescence lifetime of~1 ns is also observed.Lastly,the combined microscopic model was elaborately established to quantitatively explain the modulation of nitrogen fluorescence emission from filament by ionizing radiation.These findings provide insights into the intricate interaction among ultra-strong light field,plasma and energetic particle beam,potentially suggesting a promising novel avenue for remote sensing of ionizing radiation.展开更多
Strong feld-induced nonsequential double ionization(NSDI)is a signifcant multi-electron phenomenon that provides crucial insights into understanding electron correlation and multiple ionization of atoms and molecules,...Strong feld-induced nonsequential double ionization(NSDI)is a signifcant multi-electron phenomenon that provides crucial insights into understanding electron correlation and multiple ionization of atoms and molecules,but it is typically unattainable in a circularly polarized laser pulse,especially for long-wavelength lasers.We present evidence that NSDI can occur in the presence of a near-infrared or beyond laser pulse by introducing a bowtie-nanotip.The laser-induced local plasmon can alter the local ellipticity of the feld,thereby enabling NSDI through elliptical trajectories that facilitate recollisions with parent atoms.An oval-shaped momentum distribution of recoiled ions provides evidence for the modifcation of trajectories by the aligned nanotips.Our study introduces an innovative control knob to manipulate NSDI and electron dynamics through the utilization of nanostructures.展开更多
We present a fully time-dependent quantum wave packet evolution method for investigating molecular dynamics in intense laser fields.This approach enables the simultaneous treatment of interactions among multiple elect...We present a fully time-dependent quantum wave packet evolution method for investigating molecular dynamics in intense laser fields.This approach enables the simultaneous treatment of interactions among multiple electronic states while simultaneously tracking their time-dependent electronic,vibrational,and rotational dynamics.As an illustrative example,we consider neutral H_(2)molecules and simulate the laser-induced excitation dynamics of electronic and rotational states in strong laser fields,quantitatively distinguishing the respective contributions of electronic dipole transitions(within the classical-field approximation)and non-resonant Raman processes to the overall molecular dynamics.Furthermore,we precisely evaluate the relative contributions of direct tunneling ionization from the ground state and ionization following electronic excitation in the strong-field ionization of H_(2).The developed methodology shows strong potential for performing high-precision theoretical simulations of electronic-vibrational-rotational state excitations,ionization,and dissociation dynamics in molecules and their ions under intense laser fields.展开更多
This work describes the discharge characteristics and acetone degradation with plasma under different electric fields based on a coaxial cylindrical dielectric barrier discharge(DBD)device energized by pulsed power.It...This work describes the discharge characteristics and acetone degradation with plasma under different electric fields based on a coaxial cylindrical dielectric barrier discharge(DBD)device energized by pulsed power.It is found that the segmented electrodes with appropriate spacing in coaxial cylindrical DBD are beneficial to the plasma ionization.In this work,the plasma distribution,discharge thermal effect,ionization of reactive species,and acetone degradation performance in coaxial cylindrical DBD with different segmented electrodes are systematically investigated.The experimental results show that segmented electrodes with a certain distance can cause additional ionization in the non-electrode-covered region between adjacent electrodes,thus enlarging the plasma region compared with a single electrode with equivalent total electrode length.The additional ionization involved the inner volume discharge between the quartz tubes and the outer surface discharge along the surface of the external quartz tube.The spatial distributions of the inner volume discharge and external surface discharge were predominantly governed by the radial and axial components of the inter-electrode electric field,respectively.The external surface discharge exhibited significant suppression when the electrode spacing was<1.5 mm,and it reached its maximum length at 3 mm spacing.When the electrode distance increased to 7-9 mm,a weak ionizing region appeared in the middle of the adjacent electrodes,which could be attributed to the gradual attenuation of the radial component with the increasing electrode spacing.A higher thermal effect and better oxidation of acetone to CO_(x)(CO and CO_(2))were achieved with the segmented electrode;the dual-segment configuration(3 mm per electrode)achieved a reactor temperature of 63.4℃,representing a 10℃enhancement over comparable single-electrode systems.Similarly,the CO_(2)and CO concentration reached 328.8 mg/m3and 105.7 mg/m3,respectively,in two 3 mm long segmented electrodes,which was an increase of 12.2%and 25.6%,respectively,compared with the single electrode.Notably,considering the equivalent ionization of the inner discharge with different electrodes,the enhanced thermal effects and CO_(x)conversion efficiency directly correlate with the expanded plasma zone induced by electrode segmentation.This work provides critical insights into optimizing electrode configurations for efficient plasma-assisted volatile organic compound degradation systems.展开更多
Accurate classification of pulmonary nodules is critical for early diagnosis of lung cancer. However, non-invasive and accurate diagnosis of benign and malignant pulmonary nodules faces great challenges. In this study...Accurate classification of pulmonary nodules is critical for early diagnosis of lung cancer. However, non-invasive and accurate diagnosis of benign and malignant pulmonary nodules faces great challenges. In this study, we develop a nano zero-valent iron(nZVI)-assisted laser desorption/ionization mass spectrometry(LDI MS) platform, which enables ultra-high-throughput acquisition of abundant metabolic fingerprint information of serum in negative ion mode. We further recruit a large-scale multicenter prospective cohort and collect 1099 serum samples from participants with benign and malignant nodules. The accurate machine learning models are built and validated based on n ZVI-assisted LDI MS metabolomics to achieve efficient classification of benign and malignant nodules. Using our established stacking ensemble learning model, the AUC of the ROC curve for benign and malignant lung nodule classification can be as high as 0.9, and the sensitivity can reach 85.5%, which is significantly better than existing clinical models. This work provides an integrated workflow from detection technology to diagnostic models for biomarkerbased pulmonary nodule diagnosis, which would be widely used in rapid and large-scale screening of pulmonary nodules.展开更多
Introduction: The use of radioactive radiations in healthcare facilities must comply with radioprotection safety rules in order to avoid threatening the health of workers and patients. This study aimed to assess the w...Introduction: The use of radioactive radiations in healthcare facilities must comply with radioprotection safety rules in order to avoid threatening the health of workers and patients. This study aimed to assess the working conditions, the protective measures and the medical monitoring of workers directly involved in X-ray work at hospitals in Douala, Cameroon. Materials and Methods: A descriptive cross-sectional study was carried out during the 1st quarter of 2018, across various state and private health facilities of the city of Douala. Sampling was non-random, based on convenience and all the willing participants that fulfilled the inclusion criteria were enrolled. Quantitative analyses were conducted using EPI INFO 7.0 software and the results were presented in both univariate and bivariate forms. Results: The sample consisted of 56 men and 31 women with a mean age of 34.75 ± 8.77 years. X-ray technicians were over-represented (41.38%). Day/night shift work was the main work pattern (68.96%). The distribution of work zones A&B was known by 87.5% of the participants. Hazard warning signs were effective in work zones A and B (75.86%), and the walls of the premises were also reinforced in these work zones (88.51%), but the use of radiation dosimeters was rare (9.20%). Radiation aprons (94.30%) and hand-held dosimeters (63.20%) were the most commonly used personal protective equipment. The majority of the participants did not benefit from medical follow-up by an occupational health specialist (62.1%). Conclusion: The implementation of radiation protection measures remains a significant concern in Douala based health facilities, and requires stricter administrative controls and sanctions to prevent serious health consequences for exposed staff.展开更多
The emergence of high-temperature superconductivity in hydrogen-rich compounds has opened up promising avenues for investigating unique hydrogen motifs that exhibit exceptional superconducting properties.Nevertheless,...The emergence of high-temperature superconductivity in hydrogen-rich compounds has opened up promising avenues for investigating unique hydrogen motifs that exhibit exceptional superconducting properties.Nevertheless,the requirement for extremely high synthesis pressures poses significant barriers to experimentally probing potential physical properties.Here,we have designed a structure wherein NH_(3)tetrahedra are intercalated into the body-centered cubic lattice of Yb,resulting in the formation of Yb(NH_(3))_(4).Our first-principles calculations reveal that metallic behavior emerges from the ionization of sp^(3)-hybridized s-bonds in NH_(3),which is enabled by electron transfer from ytterbium orbitals to NH_(3)anti-bonding s-orbitals.A distinctive feature of this structure is the Fermi surface nesting,which leads to optical phonon softening and consequently enhances electron-phonon coupling.The subsequent density-functional theory(DFT)calculations demonstrate that this I-43m phase of Yb(NH_(3))4 exhibits a superconducting critical temperature(T_(c))of 17.32 K under a modest pressure of 10 GPa.Our investigation presents perspectives on achieving phonon-mediated superconductivity at relatively low pressures,thereby opening up extensive possibilities for the attainment of high-temperature superconductivity in hydrogen-based superconducting systems with specific ionized molecular groups.展开更多
Bone marrow serves as the life-long home for hemato-poietic stem cells(HSCs)and is the most radio-sensitive organ^([1]).Acute ionizing radiation exceeding 1 Gray(Gy)causes severe damage in bone marrow while no effecti...Bone marrow serves as the life-long home for hemato-poietic stem cells(HSCs)and is the most radio-sensitive organ^([1]).Acute ionizing radiation exceeding 1 Gray(Gy)causes severe damage in bone marrow while no effective drug has been approved in clinical.In a recent work pub-lished in MedComm,Gao and her team reported,for the first time,cannabidiol(CBD)as an outstanding radioprotection agent targeting acute radiation-induced hematopoietic injury^([2]).Within two weeks post radiation,CBD can pro-mote the stemness of hematopoietic stem cells to a regular level.Using single-cell RNA sequencing(scRNA-seq)and functional assay,the authors decoded molecular changes underlying radiation-induced damage and CBD-induced recovery in HSCs.展开更多
Traditional electrospray ionization tandem mass spectrometry(ESI-MS^(n))has been a powerful tool in diverse research areas,however,it faces great limitations in the study of protein-small molecule interactions.In this...Traditional electrospray ionization tandem mass spectrometry(ESI-MS^(n))has been a powerful tool in diverse research areas,however,it faces great limitations in the study of protein-small molecule interactions.In this article,the state-of-the-art temperature-controlled electrospray ionization tandem mass spectrometry(TC-ESI-MS^(n))is applied to investigate interactions between ubiquitin and two flavonol molecules,respectively.The combination of collision-induced dissociation(CID)and MS solution-melting experiments facilitates the understanding of flavonol-protein interactions in a new dimension across varying temperature ranges.While structural changes of proteins disturbed by small molecules are unseen in ESI-MS^(n),TC-ESI-MS^(n)allows a simultaneous assessment of the stability of the complex in both gas and liquid phases under various temperature conditions,meanwhile investigating the impact on the protein’s structure and tracking changes in thermodynamic data,and the characteristics of structural intermediates.展开更多
文摘Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells.To be excited,the development of ionizable drug delivery systems(IDDSs)has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019(COVID-19)in 2021.Compared with conventional cationic gene vectors,IDDSs can decrease the toxicity of carriers to cell membranes,and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures.Despite the progress,there remain necessary requirements for designing more efficient IDDSs for precise gene therapy.Herein,we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms.The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of plasmid DNA(pDNA)and four kinds of RNA.In particular,organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity.We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future,and indicate ideas for developing next generation gene vectors.
基金supported by National Key R&D Program of China(2021YFA0909900)Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education(TMIT2024Y01,China)+4 种基金Liaoning Province Applied Basic Research Program(2022JH2/101300097,China)Liaoning Province Department of Education Project(LJKMZ20221365,China)National Postdoctoral Foundation of China(2023M730375)Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(GZC20240050,China)Outstanding youth fund of Shenyang Pharmaceutical University(YQ202208,China).
文摘Tailored lipid nanoparticles(LNPs)-mediated small interfering RNA(siRNA)nanomedicines show promise in treating liver disease,such as acute liver injury(ALI)and non-alcoholic steatohepatitis(NASH).However,constructing LNPs that address biosafety concerns,ensure efficient delivery,and target specific hepatic subcellular fractions has been challenging.To evade above obstacles,we develop three novel self-degradable“gemini-like”ionizable lipids(SS-MA,SS-DC,SS-MH)by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head.Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release,improving both biosafety and siRNA delivery efficiency.Furthermore,the distance of ester bond and tertiary amino head significantly influences the LNPs’pKa,thereby affecting endosomal escape,hemolytic efficiency,absorption capacity of ApoE,uptake efficiency of hepatocytes and liver accumulation.We also develop the modified-mannose LNPs(M-LNP)to target liver macrophages specifically.The optimized M-MH_LNP@TNFa exhibits potential in preventing ALI by decreasing tumor necrosis factor a(TNFa)levels in the macrophages,while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2(DGAT2)in the hepatocytes.Our findings provide new insights into developing novel highly effective and low-toxic“gemini-like”ionizable lipids for constructing LNPs,potentially achieving more effective treatment for hepatic diseases.
基金This work was supported by the Ligue Nationale Contre le Cancer(L.P.,Z.L.)China Scholarship Council(W.L.,L.D.)+2 种基金Italian Association for Cancer Research(IG17413)(S.P.)the French National Research Agency under the frame of the H2020 Era-Net EURONANOMED European Research projects“Target4Cancer”,“NANOGLIO”,“TARBRAINFECT”,“NAN4-TUM”(L.P.),and H2020 NMBP“SAFE-N-MEDTECH”(L.P.)This article is based upon work from COST Action CA 17140“Cancer Nanomedicine from the Bench to the Bedside”supported by COST(European Cooperation in Science and Technology).
文摘Gene therapy using small interfering RNA(siRNA)is emerging as a novel therapeutic approach to treat various diseases.However,safe and efficient siRNA delivery still constitutes the major obstacle for clinical implementation of siRNA therapeutics.Here we report an ionizable supramolecular dendrimer vector,formed via self-assembly of a small amphiphilic dendrimer,as an effective siRNA delivery system with a favorable safety profile.By virtue of the ionizable tertiary amine terminals,the supramolecular dendrimer has a low positively charged surface potential and no notable cytotoxicity at physiological pH.Nonetheless,this ionizable feature imparted sufficient surface charge to the supramolecular dendrimer to enable formation of a stable complex with siRNA via electrostatic interactions.The resulting siRNA/dendrimer delivery system had a surface charge that was neither neutral,thus avoiding aggregation,nor too high,thus avoiding cytotoxicity,but was sufficient for favorable cellular uptake and endosomal release of the siRNA.When tested in different cancer cell lines and patient-derived cancer organoids,this dendrimer-mediated siRNA delivery system effectively silenced the oncogenes Myc and Akt2 with a potent antiproliferative effect,outperforming the gold standard vector,Lipofectamine 2000.Therefore,this ionizable supramolecular dendrimer represents a promising vector for siRNA delivery.The concept of supramolecular dendrimer nanovectors via self-assembly is new,yet easy to implement in practice,offering a new perspective for supramolecular chemistry in biomedical applications.
文摘The electrochemical behavior of ionizable drugs (Amitriptyline, Diphenhydramine and Trihexyphene- dyl) at the water/1,2-dichloroethane interface with the phase volume ratio (r = Vo/Vw) equal to 1 are investigated by cyclic voltammetry. The system is composed of an aqueous droplet supported at an Ag/AgCl disk electrode and it was covered with an organic solution. In this manner, a conventional three-electrode potentiostat can be used to study the ioni-zable drugs transfer process at a liquid/liquid interface. Physicochemical parameters such as the formal transfer potential, the Gibbs energy of transfer and the standard par-tition coefficients of the ionized forms of these drugs can be evaluated from cyclic voltammograms obtained. The ob-tained results have been summarized in ionic partition dia-grams, which are a useful tool for predicting and interpret-ing the transfer mechanisms of ionizable drugs at the liq-uid/liquid interfaces and biological membranes.
基金Project suppoted by the Excellent Young Scientist Award from the National Natural Science Foundation of Chinathe Natural Science Foundation of Liaoning Province.
文摘The migration mechanism of ionizable compounds in capillary electrochromatography (CEC) is more complicated than in high performance liquid chromatography (HPLC) due to the involvement of electrophoresis and the second chemical equilibrium. The separation mechanism of ionizable compounds in CEC has been studied theoretically. The electrochromatographic capacity factors of ions ( k * ) in CEC and in the pressurized CEC are derived by phenomenologi-cal approach. The influence of pH, voltage, pressure on k * is discussed. In addition, the k * of weak acid and weak base are derived based on acid-base equilibrium and the influence of pH on k is studied theoretically.
基金supported by the National Key Research and Development Program of China(No.2019YFA0905200)the National Natural Science Foundation of China(No.82072045)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.KYCX23_1504).
文摘Messenger ribonucleic acid(mRNA)-based therapeutics hold great prospects in disease treatment and lipid nanoparticles(LNPs)are the most extensively applied non-viral platform for RNA delivery in clinics.Despite the clinical success of LNPs as vehicles have been achieved,developing LNPs with enhanced mRNA transmembrane delivery and transfection efficiency in a non-toxic manner is highly desirable and challenging.In this study,we designed a series of new ionizable amino lipids with piperazinederived headgroups and constructed a group of LNPs to promote the transfection activity of mRNA cargos.Among them,LNP formulated with lipid 10(L10-LNP)can efficiently package mRNA and perform superior transfection efficiency both in vitro and in vivo,which is mainly attributed to the improved intracellular uptake and effective endosomal escape.We verified that a single administration of L10-LNP packaging interleukin(IL)-12 mRNA induced tumor shrink and even regression by robust activation of immune effector CD8^(+)T cells and stimulating the generation of IFN-γwithout causing systemic toxicity,which provides a promising platform for clinical cancer immunotherapy.
基金supported by the National Natural Science Foundation of China (Grant Nos.12325406,92261201,12404305,and W2512072)the Shaanxi Province Natural Science Fundamental Research Project (Grant Nos.2023JC-XJ-03 and23JSQ013)the China Postdoctoral Science Foundation (Grant Nos.BX20240286 and 2024M7625)。
文摘Abiotic oxygen formation predates photosynthesis,sustaining early chemical evolution,yet its elementary mechanisms remain contested.Here,we show the production pathways for molecular oxygen from doubly ionized carbon dioxide upon electron-impact.Through fragment ions and electron coincidence momentum imaging,we unambiguously determine the ionization mechanism by measuring the projectile energy loss in association with the C^(+) +O_(2)^(+) channel.Further potential energy and trajectory calculations enable us to elucidate the dynamical details of this fragmentation process,in which a bond rearrangement pathway is found to proceed via the structural deformation to a triangular intermediate.Moreover,we demonstrate a further roaming pathway for the formation of O_(2)^(+) from CO_(2)^(+) 2,in which a frustrated C-O bond cleavage leaves the O atom without sufficient energy to escape.The O atom then wanders around varied configuration spaces of the flat potential energy regions and forms a C-O-O_(2)^(+) intermediate prior to the final products C^(+) +O_(2)^(+).Considering the large quantities of free electrons in interstellar space,the processes revealed here are expected to be significant and should be incorporated into atmospheric evolution models.
基金supported in part by National R&D Program for Major Research Instruments of China(No.62027814)。
文摘This study focuses on a 60 V trench MOSFET device designed for operation in space radiation environments.By increasing the bulk region concentration and placing the etched gate trench after the P+implantation process,we successfully reduced the threshold voltage shift from 6.5 to 2.2 V under a total dose of 400 krad(Si)^(60)Co,allowing the device to operate normally.Structurally,by embedding the source metal in the active and terminal regions,the device demonstrated current degradation without experiencing single-event burnout when subjected to a drain voltage of 60 V and a linear energy transfer value of 75.4 MeV·cm^(2)∕mg from tantalum-ion incidence.TCAD simulations verified that the embedded source metal effectively suppressed parasitic transistor conduction and eliminated the base-region expansion effect,thereby lowering the maximum temperature from 8000 to 1400 K.The irradiation effects of the embedded source metal in the terminal region were also investigated,which can improve the reverse recovery and ensure that the terminal metal does not melt prematurely,thereby significantly enhancing the radiation hardness of the device.
基金supported by the National Natural Science Foundation of China(22325602,22521201,22176060,and 22406142)the"National Key R&D Program of China"(SQ2024YFA1211001)+3 种基金the Program of Shanghai Academic/Technology Research Leader(23XD1421000)Key Laboratory of Functional Inorganic Material Chemistry(Heilongjiang University)Ministry of Education(KIM-0-2025017)State Key Laboratory of Water Pollution Control and Green Resource Recycling Foundation(PCRRF250014).
文摘The efficient and sustainable removal of refractory high ionization potential(high-IP)organic pollutants remains challenging due to their redox inertness and poor interfacial electron transfer.Herein,we report a suspended photo-Fenton membrane (2D-C_(3)N_(4)/Fe-N-C/GO) that circumvents these limitations via a self-sufficient oxidant generation pathway,enabling low-carbon abatement of high-IP pollutants.This multifunctional architecture couples the visible-light-driven production of hydrogen peroxide(H_(2)O_(2)) by two-dimensional carbon nitride(2D-C_(3)N_(4)) with the Fe-N-C mediated adsorption and activation of electron-deficient species via pyridinic N-Fe^(2+)/Fe^(3+) redox pairs.Under light irradiation,photogenerated electrons continuously regenerate Fe^(2+) from Fe^(3+),sustaining reactive oxygen species(·OH)production and promoting efficient oxidative mineralization.The system demonstrates robust long-term performance in both synthetic and real wastewater matrices,achieving superior degradation and chemical oxygen demand(COD)removal.Life cycle assessment(LCA)confirms its environmental superiority over conventional homogeneous Fenton processes,with markedly reduced carbon emissions and ecological impacts.This work offers a mechanistically insightful and practically viable platform for the green,efficient,and durable remediation of high-IP organic pollutants,providing conceptual guidance for next-generation catalytic wastewater treatment technologies.
基金supported by the National Natural Science Foundation of China(U2241221).
文摘This article introduces a novel 20 V radiation-hardened high-voltage metal-oxide-semiconductor field-effect transistor(MOSFET)driver with an optimized input circuit and a drain-surrounding-source(DSS)structure.The input circuit of a conventional inverter consists of a thick-gate-oxide n-type MOSFET(NMOS).These conventional drivers can tolerate a total ionizing dose(TID)of up to 100 krad(Si).In contrast,the proposed comparator input circuit uses both a thick-gate-oxide p-type MOSFET(PMOS)and thin-gate-oxide NMOS to offer a high input voltage and higher TID tolerance.Because the thick-gate-oxide PMOS and thin-gate-oxide NMOS collectively provide better TID tolerance than the thick-gate-oxide NMOS,the circuit exhibits enhanced TID tolerance of>300 krad(Si).Simulations and experimental date indicate that the DSS structure reduces the probability of unwanted parasitic bipolar junction transistor activation,yielding a better single-event effect tolerance of over 81.8 MeVcm^(2)mg^(-1).The innovative strategy proposed in this study involves circuit and layout design optimization,and does not require any specialized process flow.Hence,the proposed circuit can be manufactured using common commercial 0.35μm BCD processes.
基金supported by the National Special Fund for the Development of Major Research Equipment and Instrument(No.2020YFF01014503)the Young Taishan Scholars(No.tsqn201909039)the College 20 Project fromJi Nan Science&Technology Bureau(No.2021GXRC058).
文摘Formic and acetic acids are the most abundant gaseous organic acids and play the key role in the atmospheric chemistry.In iodine-adduct chemical ionizationmass spectrometry(CIMS),the low utilization efficiency of methyl iodide and humidity interference are two major issues of the vacuum ultraviolet(VUV)lamp initiated CIMS for on-line gaseous formic and acetic acids analysis.In this work,we present a new CIMS based on VUV lamp,and the ion-molecular reactor is separated into photoionization and chemical ionization zones by a reducer electrode.Acetone was added to the photoionization zone,and the VUV photoionization acetone provided low-energy electrons for methyl iodide to generate I−,and the addition of acetone reduced the amount of methyl iodide by 2/3.In the chemical ionization zone,a headspace vial containing ultrapure water was added for humidity calibration,and the vial changes the sensitivity as a function of humidity from ambiguity to well linear correlation(R2>0.95).With humidity calibration,the CIMS can quantitatively measure formic and acetic acids in the humidity range of 0%-88%RH.In this mode,limits of detection of 10 and 50 pptv are obtained for formic and acetic acids,respectively.And the relative standard deviation(RSD)of quantitation stability for 6 days were less than 10.5%.This CIMS was successfully used to determine the formic and acetic acids in the underground parking and ambient environment of the Shandong University campus(Qingdao,China).In addition,we developed a simple model based formic acid concentration to assess vehicular emissions.
基金financial supports from National Key Research and Development Program of China(2024YFB3613900)National Natural Science Foundation of China(W2412044)+1 种基金Russian Science Foundation(25-4900154)Fundamental Research Funds for the Central Universities(63253214)。
文摘Accidental exposure to overdose ionizing radiation will inevitably lead to severe biological damage,thus detecting and localizing radiation is essential.Traditional measurement techniques are generally restricted to the detection range of few centimeters,posing a great risk to operators.The prospect in remote sensing makes femtosecond laser filament technology a great candidate for constructively addressing this challenge.Here we propose a novel filament-based ionizing radiation sensing method,and clarify the interaction mechanism between filaments and ionizing radiation from systematic experiment to microscopic theory.Specifically,it is demonstrated that the energetic electrons produced byαradiation in air can be effectively accelerated within the filament,serving as seed electrons,which will enhance nitrogen fluorescence.The extended nitrogen fluorescence lifetime of~1 ns is also observed.Lastly,the combined microscopic model was elaborately established to quantitatively explain the modulation of nitrogen fluorescence emission from filament by ionizing radiation.These findings provide insights into the intricate interaction among ultra-strong light field,plasma and energetic particle beam,potentially suggesting a promising novel avenue for remote sensing of ionizing radiation.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFE0134200)the National Natural Science Foundation of China(Grant Nos.12474343,12174147,and 12074142)the Natural Science Foundation of Jilin Province,China(Grant No.20220101016JC)。
文摘Strong feld-induced nonsequential double ionization(NSDI)is a signifcant multi-electron phenomenon that provides crucial insights into understanding electron correlation and multiple ionization of atoms and molecules,but it is typically unattainable in a circularly polarized laser pulse,especially for long-wavelength lasers.We present evidence that NSDI can occur in the presence of a near-infrared or beyond laser pulse by introducing a bowtie-nanotip.The laser-induced local plasmon can alter the local ellipticity of the feld,thereby enabling NSDI through elliptical trajectories that facilitate recollisions with parent atoms.An oval-shaped momentum distribution of recoiled ions provides evidence for the modifcation of trajectories by the aligned nanotips.Our study introduces an innovative control knob to manipulate NSDI and electron dynamics through the utilization of nanostructures.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFA1602502)the National Natural Science Foundation of China(Grant No.12450404)。
文摘We present a fully time-dependent quantum wave packet evolution method for investigating molecular dynamics in intense laser fields.This approach enables the simultaneous treatment of interactions among multiple electronic states while simultaneously tracking their time-dependent electronic,vibrational,and rotational dynamics.As an illustrative example,we consider neutral H_(2)molecules and simulate the laser-induced excitation dynamics of electronic and rotational states in strong laser fields,quantitatively distinguishing the respective contributions of electronic dipole transitions(within the classical-field approximation)and non-resonant Raman processes to the overall molecular dynamics.Furthermore,we precisely evaluate the relative contributions of direct tunneling ionization from the ground state and ionization following electronic excitation in the strong-field ionization of H_(2).The developed methodology shows strong potential for performing high-precision theoretical simulations of electronic-vibrational-rotational state excitations,ionization,and dissociation dynamics in molecules and their ions under intense laser fields.
文摘This work describes the discharge characteristics and acetone degradation with plasma under different electric fields based on a coaxial cylindrical dielectric barrier discharge(DBD)device energized by pulsed power.It is found that the segmented electrodes with appropriate spacing in coaxial cylindrical DBD are beneficial to the plasma ionization.In this work,the plasma distribution,discharge thermal effect,ionization of reactive species,and acetone degradation performance in coaxial cylindrical DBD with different segmented electrodes are systematically investigated.The experimental results show that segmented electrodes with a certain distance can cause additional ionization in the non-electrode-covered region between adjacent electrodes,thus enlarging the plasma region compared with a single electrode with equivalent total electrode length.The additional ionization involved the inner volume discharge between the quartz tubes and the outer surface discharge along the surface of the external quartz tube.The spatial distributions of the inner volume discharge and external surface discharge were predominantly governed by the radial and axial components of the inter-electrode electric field,respectively.The external surface discharge exhibited significant suppression when the electrode spacing was<1.5 mm,and it reached its maximum length at 3 mm spacing.When the electrode distance increased to 7-9 mm,a weak ionizing region appeared in the middle of the adjacent electrodes,which could be attributed to the gradual attenuation of the radial component with the increasing electrode spacing.A higher thermal effect and better oxidation of acetone to CO_(x)(CO and CO_(2))were achieved with the segmented electrode;the dual-segment configuration(3 mm per electrode)achieved a reactor temperature of 63.4℃,representing a 10℃enhancement over comparable single-electrode systems.Similarly,the CO_(2)and CO concentration reached 328.8 mg/m3and 105.7 mg/m3,respectively,in two 3 mm long segmented electrodes,which was an increase of 12.2%and 25.6%,respectively,compared with the single electrode.Notably,considering the equivalent ionization of the inner discharge with different electrodes,the enhanced thermal effects and CO_(x)conversion efficiency directly correlate with the expanded plasma zone induced by electrode segmentation.This work provides critical insights into optimizing electrode configurations for efficient plasma-assisted volatile organic compound degradation systems.
基金financially supported by the Fundamental Research Funds for the Central Universities (No. WHU 2042024kf0009)National Key Research and Development Program of China (No. 2021YFC2700700)the National Natural Science Foundation of China (Nos. 22074111, 22004093)。
文摘Accurate classification of pulmonary nodules is critical for early diagnosis of lung cancer. However, non-invasive and accurate diagnosis of benign and malignant pulmonary nodules faces great challenges. In this study, we develop a nano zero-valent iron(nZVI)-assisted laser desorption/ionization mass spectrometry(LDI MS) platform, which enables ultra-high-throughput acquisition of abundant metabolic fingerprint information of serum in negative ion mode. We further recruit a large-scale multicenter prospective cohort and collect 1099 serum samples from participants with benign and malignant nodules. The accurate machine learning models are built and validated based on n ZVI-assisted LDI MS metabolomics to achieve efficient classification of benign and malignant nodules. Using our established stacking ensemble learning model, the AUC of the ROC curve for benign and malignant lung nodule classification can be as high as 0.9, and the sensitivity can reach 85.5%, which is significantly better than existing clinical models. This work provides an integrated workflow from detection technology to diagnostic models for biomarkerbased pulmonary nodule diagnosis, which would be widely used in rapid and large-scale screening of pulmonary nodules.
文摘Introduction: The use of radioactive radiations in healthcare facilities must comply with radioprotection safety rules in order to avoid threatening the health of workers and patients. This study aimed to assess the working conditions, the protective measures and the medical monitoring of workers directly involved in X-ray work at hospitals in Douala, Cameroon. Materials and Methods: A descriptive cross-sectional study was carried out during the 1st quarter of 2018, across various state and private health facilities of the city of Douala. Sampling was non-random, based on convenience and all the willing participants that fulfilled the inclusion criteria were enrolled. Quantitative analyses were conducted using EPI INFO 7.0 software and the results were presented in both univariate and bivariate forms. Results: The sample consisted of 56 men and 31 women with a mean age of 34.75 ± 8.77 years. X-ray technicians were over-represented (41.38%). Day/night shift work was the main work pattern (68.96%). The distribution of work zones A&B was known by 87.5% of the participants. Hazard warning signs were effective in work zones A and B (75.86%), and the walls of the premises were also reinforced in these work zones (88.51%), but the use of radiation dosimeters was rare (9.20%). Radiation aprons (94.30%) and hand-held dosimeters (63.20%) were the most commonly used personal protective equipment. The majority of the participants did not benefit from medical follow-up by an occupational health specialist (62.1%). Conclusion: The implementation of radiation protection measures remains a significant concern in Douala based health facilities, and requires stricter administrative controls and sanctions to prevent serious health consequences for exposed staff.
基金work was supported by the National Key Research and Development Program of China(Grant Nos.2023YFA1406200 and 2022YFA1405500)the National Natural Science Foundation of China(Grant Nos.12304021 and 52072188)+4 种基金Zhejiang Provincial Natural Science Foundation of China(Grant No.LQ23A040004)Program for Science and Technology Innovation Team in Zhejiang(Grant No.2021R01004)the Natural Science Foundation of Ningbo(Grant No.2022J091)the Program for Changjiang Scholars and Innovative Research Team in University(Grant No.IRT 15R23)Parts of calculations were performed at the Supercomputer Center of Ningbo University.
文摘The emergence of high-temperature superconductivity in hydrogen-rich compounds has opened up promising avenues for investigating unique hydrogen motifs that exhibit exceptional superconducting properties.Nevertheless,the requirement for extremely high synthesis pressures poses significant barriers to experimentally probing potential physical properties.Here,we have designed a structure wherein NH_(3)tetrahedra are intercalated into the body-centered cubic lattice of Yb,resulting in the formation of Yb(NH_(3))_(4).Our first-principles calculations reveal that metallic behavior emerges from the ionization of sp^(3)-hybridized s-bonds in NH_(3),which is enabled by electron transfer from ytterbium orbitals to NH_(3)anti-bonding s-orbitals.A distinctive feature of this structure is the Fermi surface nesting,which leads to optical phonon softening and consequently enhances electron-phonon coupling.The subsequent density-functional theory(DFT)calculations demonstrate that this I-43m phase of Yb(NH_(3))4 exhibits a superconducting critical temperature(T_(c))of 17.32 K under a modest pressure of 10 GPa.Our investigation presents perspectives on achieving phonon-mediated superconductivity at relatively low pressures,thereby opening up extensive possibilities for the attainment of high-temperature superconductivity in hydrogen-based superconducting systems with specific ionized molecular groups.
文摘Bone marrow serves as the life-long home for hemato-poietic stem cells(HSCs)and is the most radio-sensitive organ^([1]).Acute ionizing radiation exceeding 1 Gray(Gy)causes severe damage in bone marrow while no effective drug has been approved in clinical.In a recent work pub-lished in MedComm,Gao and her team reported,for the first time,cannabidiol(CBD)as an outstanding radioprotection agent targeting acute radiation-induced hematopoietic injury^([2]).Within two weeks post radiation,CBD can pro-mote the stemness of hematopoietic stem cells to a regular level.Using single-cell RNA sequencing(scRNA-seq)and functional assay,the authors decoded molecular changes underlying radiation-induced damage and CBD-induced recovery in HSCs.
基金supports by the National Natural Science Foundation of China(No.22174037)the Joint Funds of the Hunan Provincial Natural Science Foundation of China(No.2023JJ50255)+1 种基金Changsha Science and Technology Project(No.Z202269490128)National Key Research and Development Program of China(No.2023YFF0613400)are appreciated.
文摘Traditional electrospray ionization tandem mass spectrometry(ESI-MS^(n))has been a powerful tool in diverse research areas,however,it faces great limitations in the study of protein-small molecule interactions.In this article,the state-of-the-art temperature-controlled electrospray ionization tandem mass spectrometry(TC-ESI-MS^(n))is applied to investigate interactions between ubiquitin and two flavonol molecules,respectively.The combination of collision-induced dissociation(CID)and MS solution-melting experiments facilitates the understanding of flavonol-protein interactions in a new dimension across varying temperature ranges.While structural changes of proteins disturbed by small molecules are unseen in ESI-MS^(n),TC-ESI-MS^(n)allows a simultaneous assessment of the stability of the complex in both gas and liquid phases under various temperature conditions,meanwhile investigating the impact on the protein’s structure and tracking changes in thermodynamic data,and the characteristics of structural intermediates.
