Stroke is the second leading cause of disability and mortality worldwide,imposing a substantial socioeconomic burden on individuals and healthcare systems.Annually,approximately 14 million people experience stroke,wit...Stroke is the second leading cause of disability and mortality worldwide,imposing a substantial socioeconomic burden on individuals and healthcare systems.Annually,approximately 14 million people experience stroke,with ischemic stroke comprising nearly 85%of cases,of which 10%to 20%involve large vessel occlusions.Currently,recombinant tissue plasminogen activator(tPA)remains the only approved pharmacological intervention.However,its utility is limited due to a narrow therapeutic window and low recanalization rates,making it applicable to only a minority of patients.Therefore,there is an urgent need for novel therapeutic strategies,including pharmacological advancements and combinatory treatments.Small-molecule natural medicines,particularly those derived from traditional Chinese herbs,have demonstrated significant therapeutic potential in ischemic stroke management.These compounds exert multiple neuroprotective effects,such as antioxidation,anti-inflammatory action,and inhibition of apoptosis,all of which are critical in mitigating stroke-induced cerebral damage.This review comprehensively examines the pathophysiology of acute ischemic stroke(AIS)and highlights the recent progress in the development of small-molecule natural medicines as promising therapeutic agents for cerebral ischemic stroke.展开更多
OBJECTIVE:To explore if Hewei Jiangni granule(和胃降逆颗粒,HWJNG)could regulate esophageal hypersensitivity via stromal interaction molecule 1(STIM1)/transient receptor potential vanilloid subfamily member 1(TRPV1)pat...OBJECTIVE:To explore if Hewei Jiangni granule(和胃降逆颗粒,HWJNG)could regulate esophageal hypersensitivity via stromal interaction molecule 1(STIM1)/transient receptor potential vanilloid subfamily member 1(TRPV1)pathway.METHODS:Qualitative analysis of HWJNG was analysis by high performance of liquid and gas chromatography.In vivo,animal model of non-erosive reflux disease(NERD)was established by fructose intake and restraint stress.HWJNG and Omeprazole were administered by gavage to the drug intervention group.Reflux and visceral hypersensitivity were analyzed by pathological changes,PH value test,mechanical paw withdrawal threshold,thermal withdrawal latency and mast cells(MCs)degranulation.In vitro,substance P(SP)-induced P815 cells and dorsal root ganglion(DRG)cells were cocultured.Expression in both mice and cells of STIM1,TRPV1,and esophageal visceral hypersensitivity-related gastrointestinal neurochemicals were validated by enzyme linked immunosorbent assays,quantitative realtime polymerase chain reaction(qRT-PCR)and Western blot.Moreover,overexpression and small interfering RNA against STIM1 were utilized to verify of the role of HWJNG in DRG cells.RESULTS:HWJNG significantly suppressed intercellular space widening,injury of mitochondrial,MCs degranulation,mechanical allodynia and heat neuropathic sensory and increased pH value of esophageal mucosa in NERD mice.HWJNG inhibited expression of visceral hypersensitivityrelated gastrointestinal neurochemicals in esophageal mucosa and activated P815 cells,and expression of the STIM1,TRPV1 and related neurotransmitters in DRG and DRG cells.STIM1 siRNA and HWJNG both reduced P815 cells adhesion to DRGs cells and Ca2+flow into the cytoplasmic space of DRG cells.Furthermore,HWJNG could reversed STIM1 overexpression induced upregulation of TRPV1.CONCLUSION:HWJNG suppressed intercellular space widening in NERD mice,stabilized MCs and restored neuronal hyperexcitability by regulating visceral hypersensitivity via STIM1/TRPV1 pathway.展开更多
Acceptor-donor-acceptor(A-D-A)type molecules,of which the novel non-fused azacyclic end-group pyrazoli-nones were modified with chlorine substitution on the phenyl ring,were synthesized.The non-fused azacyclic end-gro...Acceptor-donor-acceptor(A-D-A)type molecules,of which the novel non-fused azacyclic end-group pyrazoli-nones were modified with chlorine substitution on the phenyl ring,were synthesized.The non-fused azacyclic end-group py-razolinones have the advantages of simple synthesis steps,low cost and environmental friendliness,compared to the classical end-group dicyanomethyleneindianone.The properties of the synthesized A-D-A type molecules with non-fused azacyclic end groups were characterized by theoretical calculation,UV-vis absorption,cyclic voltammetry,X-ray diffraction and space charge limited current.It is shown that the strong UV-vis absorptions of the synthesized A-D-A type molecules are located in the wavelength range of 500~700 nm,with a moderate band gap of nearly 1.7 eV.At the same time,the influence of end-group chlorination on the properties of A-D-A type molecules was compared and explored.It is proven that this kind of A-D-A type molecule with non-fused azacyclic end groups has the potential to be applied as interfacial modified layer of the active layer in perovskite solar cell devices.展开更多
A tetranuclear Ln(Ⅲ)-based complex:[Dy_(4)(dbm)_(4)(L)_(6)(μ_(3)-OH)_(2)]·CH_(3)CN(1)(HL=5-[(4-methylbenzylidene)amino]quinolin-8-ol,Hdbm=dibenzoylmethane)was manufactured and its structure was characterized in...A tetranuclear Ln(Ⅲ)-based complex:[Dy_(4)(dbm)_(4)(L)_(6)(μ_(3)-OH)_(2)]·CH_(3)CN(1)(HL=5-[(4-methylbenzylidene)amino]quinolin-8-ol,Hdbm=dibenzoylmethane)was manufactured and its structure was characterized in detail.Xray diffraction analysis shows that complex 1 belongs to the monoclinic crystal system and its space group is P2_1/n,which contains a rhombic Dy_(4)core.Magnetic measurements of 1 suggest it possesses extraordinary single-molecule magnet(SMM)behavior.Its energy barrier U_(eff)/k_(B)was 116.7 K,and the pre-exponential coefficient τ_(0)=1.05×10~(-8)s.CCDC:2359322.展开更多
The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration.Axons and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are...The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration.Axons and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start networks.Here we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal cells.In this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)cDNA.To investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were used.Neurite outgrowth is evaluated through the segmentation and measurement of neural processes.These neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite growth.These neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal HT22.DDQ-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-tubulin.Additionally,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic outgrowth.Our findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara cteristics.The key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.展开更多
CRISPR-based tran-scription regulators(CRISPR-TRs)have revolutionized the field of synthetic biol-ogy by enabling tar-geted activation or repression of any de-sired gene.However,the majority of exist-ing inducible CRI...CRISPR-based tran-scription regulators(CRISPR-TRs)have revolutionized the field of synthetic biol-ogy by enabling tar-geted activation or repression of any de-sired gene.However,the majority of exist-ing inducible CRISPR-TRs are limited by their dependence on specific sequences,which restricts their flex-ibility and controllability in genetic engineering applications.In this study,we proposed a novel strategy to construct sequence-independent inducible CRISPR-TRs,which is achieved by the design of stem loop 2 in the single guide RNA(sgRNA).Under this strategy,by utiliz-ing toehold-mediated strand displacement(TMSD)reactions between small endogenous molecules(miR-20a and TK1 mRNA)and bridge RNA(bRNA)to link bRNA with sgRNA,we achieved synergistic transcriptional activation of VP64 and p65-HSF1 in response to en-dogenous molecules.To enable response to exogenous molecules,we added response se-quences and bRNA sequences to the 5'end of sgRNA to block sgRNA activity,and achieved activation of sgRNA by shearing the response sequence,called sequential unlimited interlock-ing(SUI).Compared with conventional sequence-restricted interlocking(spacer-blocking hairpin(SBH)),the transcriptional activation ratio between response and non-response to the Cas6A protein using our approach was increased by 2.28-fold.Our work presents a modular and versatile framework for endogenous and exogenous molecule-responsive CRISPR-TRs in mammalian cells,without limitations imposed by sequence dependence.展开更多
In the last few years,research on advanced ultrafast photonic devices has attracted great interest from laser physicists.As a semiconductor material with excellent nonlinear saturation absorption characteristics,Ga As...In the last few years,research on advanced ultrafast photonic devices has attracted great interest from laser physicists.As a semiconductor material with excellent nonlinear saturation absorption characteristics,Ga As has been used in solidstate and fiber lasers as a mode-locker.However,the pulse widths that have been reported in the searchable published literature are all long and the shortest is tens of picoseconds.Femtosecond pulse widths,desired for a variety of applications,have not yet been reported in Ga As-based pulsed lasers.In this work,we further explore the nonlinear characteristics of Ga As that has been magnetron sputtered onto the surface of a tapered fiber and its application in the generation of femtosecond lasing via effective dispersion optimization and nonlinearity management.With the enhanced interaction between evanescent waves and Ga As nanosheets,mode-locked soliton pulses as short as 830 fs are generated at repetition rates of 4.64 MHz.As far as we know,this is the first time that femtosecond-level pulses have been generated with a Ga As-based saturable absorber.In addition,soliton molecules,including in the dual-pulse state,are also realized under stronger pumping.This work demonstrates that Ga As-based photonic devices have good application prospects in effective polymorphous ultrashort pulsed laser generation.展开更多
Soliton molecules are fascinating phenomena in ultrafast lasers which have potential for increasing the capacity of fiber optic communication.The investigation of reliable materials will be of great benefit to the gen...Soliton molecules are fascinating phenomena in ultrafast lasers which have potential for increasing the capacity of fiber optic communication.The investigation of reliable materials will be of great benefit to the generation of soliton molecules.Herein,an all-fiber laser cavity was built incorporating carbon nanotubes-based saturable absorber.Mode-locked pulses were obtained at 1565.0 nm with a 60 dB SNR and a 4.5 W peak power.Soliton molecules were subsequently observed after increasing the pump power and tuning polarization state in the same cavity,showing variable separation of pulses between 4.87 and 25.76 ps.Furthermore,these tunable soliton molecules were verified and investigated through numerical simulation,where the tuning of pump power and polarization state were simulated.These results demonstrate that soliton molecules are promising to be applied in optical communication,where carbon nanotube-based mode-locked fiber lasers serve as a reliable platform for the generation of these soliton molecules.展开更多
The task of molecule generation guided by specific text descriptions has been proposed to generate molecules that match given text inputs.Mainstream methods typically use simplified molecular input line entry system(S...The task of molecule generation guided by specific text descriptions has been proposed to generate molecules that match given text inputs.Mainstream methods typically use simplified molecular input line entry system(SMILES)to represent molecules and rely on diffusion models or autoregressive structures for modeling.However,the one-to-many mapping diversity when using SMILES to represent molecules causes existing methods to require complex model architectures and larger training datasets to improve performance,which affects the efficiency of model training and generation.In this paper,we propose a text-guided diverse-expression diffusion(TGDD)model for molecule generation.TGDD combines both SMILES and self-referencing embedded strings(SELFIES)into a novel diverse-expression molecular representation,enabling precise molecule mapping based on natural language.By leveraging this diverse-expression representation,TGDD simplifies the segmented diffusion generation process,achieving faster training and reduced memory consumption,while also exhibiting stronger alignment with natural language.TGDD outperforms both TGM-LDM and the autoregressive model MolT5-Base on most evaluation metrics.展开更多
Biomolecular condensates,also known as membraneless organelles,play a crucial role in cellular organization by concentrating or sequestering biomolecules.Despite their importance,synthetically mimicking these organell...Biomolecular condensates,also known as membraneless organelles,play a crucial role in cellular organization by concentrating or sequestering biomolecules.Despite their importance,synthetically mimicking these organelles using non-peptidic small organic molecules has posed a significant challenge.The present study reports the discovery of D008,a self-assembling small molecule that sequesters a unique subset of RNA-binding proteins.Analysis and screening of a comprehensive collection of approximately 1 million compounds in the Chinese National Compound Library(Shanghai)identified 44 self-assembling small molecules in aqueous solutions.Subsequent screening of the focused library,coupled with proteome analysis,led to the discovery of D008 as a small organic molecule with the ability to condensate a specific subset of RNA-binding proteins.In vitro experiments demonstrated that the D008-induced sequestration of RNA-binding proteins impeded mRNA translation.D008 may offer a unique opportunity for studying the condensations of RNA-binding proteins and for developing an unprecedented class of small molecules that control gene expression.展开更多
The recently demonstrated methods for cooling and trapping diatomic molecules offer new possibilities for precision searches in fundamental physical theories.Here,we propose to study the variations of the fine-structu...The recently demonstrated methods for cooling and trapping diatomic molecules offer new possibilities for precision searches in fundamental physical theories.Here,we propose to study the variations of the fine-structure constant(α=e^(2)/(hc)) and the proton-to-electron mass ratio(μ=m_(p)/m_(e)) with time by taking advantage of the nearly degenerate rovibrational levels in the electronic states of the magnesium fluoride(MgF) molecule.Specifically,due to the cancellation between the fine-structure splitting and the rovibrational intervals in the different MgF natural isotopes,a degeneracy occurs for A^(2)П_(3/2)(v'=0,J'=18.5,-) and A^(2)П_(1/2)(v "=0,J" =20.5,-).We find that using the nearly degenerate energy level of such states can be 104 times more sensitive than using a pure rotational transition to measure the variations of α and μ.To quantify the small gap between A^(2)П_(3/2)(v'=0,J'=18.5,-) and A^(2)П_(1/2)(v "=0,J" =20.5,-),special transitions of choice are feasible:X^(2)Σ_(1/2)~+(v=0,J=19.5,+) to A^(2)П_(3/2)(v'=0,J'=18.5,-) and X^(2)Σ_(1/2)~+(v=0.J=19.5,+)to A^(2)П_(1/2)(v "=0,J" =20.5,-).In addition,we estimate the frequency uncertainties caused by the narrow linewidth,Zeeman shift,Stark shift,Doppler broadening and blackbody radiation.展开更多
Molecular high-order harmonic spectroscopy is a significant advancement in ultrafast science, enabling the measurement of multielectron dynamics with attosecond temporal resolution. The fine structures observed in the...Molecular high-order harmonic spectroscopy is a significant advancement in ultrafast science, enabling the measurement of multielectron dynamics with attosecond temporal resolution. The fine structures observed in the molecular harmonic spectrum provide crucial insights into the structural or multielectron dynamical effects induced by intense laser fields. In this study, we measure the high-order harmonic spectrum of aligned CO_(2) molecules contributed from short trajectories. Two distinct groups of minima are identified in the plateau region. Our findings indicate that the deeper-lying molecular orbitals and two-center interference play significant roles in molecular harmonic generation. The results pave the way for advancing the understanding of multielectron dynamics in polyatomic molecules under intense laser fields.展开更多
Immunotherapy has transformed cancer treatment,marked by the approval of numerous antibody-based drugs.However,the limitations of antibodies in pharmacokinetics including long half-lives,limited oral bioavailability a...Immunotherapy has transformed cancer treatment,marked by the approval of numerous antibody-based drugs.However,the limitations of antibodies in pharmacokinetics including long half-lives,limited oral bioavailability and immunogenicity,have prompted the pursuit of small molecule-based immunotherapy.Traditional drug discovery strategies,which focus on blocking protein activity through inhibitors,face persistent hurdles,such as reliance on accessible binding pockets,poor selectivity,and the emergence of drug resistance.Targeted protein degradation(TPD)technologies have emerged as powerful tools to address these limitations,offering significant therapeutic advantages over conventional inhibition strategies,particularly for historically "undruggable" targets.In recent years,small molecule-based protein degraders have rapidly advanced in cancer immunotherapy.In this review,we highlight recent progress in TPD-driven small-molecule drug discovery and summarize the application of these technologies in cancer immunotherapy,including degraders targeting PD-1/PD-L1,chemokine receptors,IDO1,AhR,and others.展开更多
An in-depth understanding of the hydration mechanism of tricalcium silicate is an important basis for optimizing cement strength development.In this study,the adsorption of water molecules onto the M3-C3S(001)surface ...An in-depth understanding of the hydration mechanism of tricalcium silicate is an important basis for optimizing cement strength development.In this study,the adsorption of water molecules onto the M3-C3S(001)surface at different water coverage levels(θ=1/5,2/5,3/5,4/5,and 1)was investigated using first-principles calculations.The results demonstrate that the conclusions obtained for single water molecule adsorption cannot be fully applied to multiple water molecule adsorption.The total adsorption energies become more negative with increasing water coverage,while the average adsorption energy of each water molecule becomes more positive with increasing water coverage.The water–water interactions reduce the water–surface interactions and are responsible for the anticooperative adsorption of multiple water molecules onto M3-C_(3)S(001).The formation of Ca–OH(–Ca)bonds favors the detachment of Ca from co-valent oxygen,which reveals the significant role of dissociative adsorption.This work aims to extend the water adsorption study on M3-C3S(001)from single water molecule adsorption to multiple water molecule adsorption,providing more detailed insights into the initial water reaction on the C3S surface.展开更多
Cancer is a serious global health issue,and exploring effective treatment methods is of great significance for cancer prevention and control.Carbon monoxide(CO),as an important gas signaling molecule in the life syste...Cancer is a serious global health issue,and exploring effective treatment methods is of great significance for cancer prevention and control.Carbon monoxide(CO),as an important gas signaling molecule in the life system,has been proven to have good anti-cancer effects.However,how to controllably,safely,and effectively deliver CO to the tumor site for clinical treatment remains a challenge.Herein,a new metal-free CO-releasing molecule COR-XAC was developed for controlling CO release and cancer therapy.COR-XAC is based on the hybrid of 3-hydroxyl flavone and oxanthracene fluorophores,showing visible light-controlled CO-releasing properties and near-infrared(NIR)ratiometric fluorescence changes at 690 and 760 nm.COR-XAC shows low cytotoxicity and can be successfully applied to release CO in cells and tumors,and the CO-releasing and delivery process could be monitored by its own NIR ratiometric fluorescence changes.More importantly,the anti-cancer performance of COR-XAC was evaluated in 4T1 tumor mice,and it was found that COR-XAC plus light illumination showed excellent tumor inhibition effect,which provided a promising new effective method for cancer treatment.展开更多
Quantum algorithms offer more enhanced computational efficiency in comparison to their classical counterparts when solving specific tasks.In this study,we implement the quantum permutation algorithm utilizing a polar ...Quantum algorithms offer more enhanced computational efficiency in comparison to their classical counterparts when solving specific tasks.In this study,we implement the quantum permutation algorithm utilizing a polar molecule within an external electric field.The selection of the molecular qutrit involves the utilization of field-dressed states generated through the pendular modes of SrO.Through the application of multi-target optimal control theory,we strategically design microwave pulses to execute logical operations,including Fourier transform,oracle U_(f)operation,and inverse Fourier transform within a three-level molecular qutrit structure.The observed high fidelity of our outcomes is intricately linked to the concept of the quantum speed limit,which quantifies the maximum speed of quantum state manipulation.Subsequently,we design the optimized pulse sequence to successfully simulate the quantum permutation algorithm on a single SrO molecule,achieving remarkable fidelity.Consequently,a quantum circuit comprising a single qutrit suffices to determine permutation parity with just a single function evaluation.Therefore,our results indicate that the optimal control theory can be well applied to the quantum computation of polar molecular systems.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
Soliton molecules(SMs),bounded and self-assembled of particle-like dissipative solitons,exist with versatile mutual interactions and manifest substantial potential in soliton communication and optical data storage.How...Soliton molecules(SMs),bounded and self-assembled of particle-like dissipative solitons,exist with versatile mutual interactions and manifest substantial potential in soliton communication and optical data storage.However,controllable manipulation of the bounded molecular patterns remains challenging,as reaching a specific operation regime in lasers generally involves adjusting multiple control parameters in connection with a wide range of accessible pulse dynamics.An evolutionary algorithm is implemented for intelligent control of SMs in a 2μm ultrafast fiber laser mode locked through nonlinear polarization rotation.Depending on the specifications of the merit function used for the optimization procedure,various SM operations are obtained,including spectra shape programming and controllable deterministic switching of doublet and triplet SMs operating in stationary or pulsation states with reconfigurable temporal separations,frequency locking of pulsation SMs,doublet and SM complexes with controllable pulsation ratio,etc.Digital encoding is further demonstrated in this platform by employing the self-assembled characteristics of SMs.Our work opens up an avenue for active SM control beyond conventional telecom bands and brings useful insights into nonlinear science and applications.展开更多
Exploring multifunctional interfacial modifiers is an effective approach to addressing interface issues in perovskite solar cells(PSCs)and improving device performance and stability.While most interfacial modifiers fo...Exploring multifunctional interfacial modifiers is an effective approach to addressing interface issues in perovskite solar cells(PSCs)and improving device performance and stability.While most interfacial modifiers focus on passivating defects at the interfaces,there has been limited investigation into the relationship between molecular design and interfacial charge dynamics.This work introduces resonance molecules with a push-pull effect for interfacial modification,allowing for synergistic regulation of passivation effects and charge dynamics.Specifically,FCz-PO,which includes an electron-withdrawing fluorine atom,exhibits superior passivation but poor molecular stacking and charge extraction.In contrast,MCz-PO,featuring an electron-donating methoxy group,provides effective passivation,wellordered molecular packing,and efficient charge extraction and transport.Consequently,PSCs using MCz-PO achieve high power conversion efficiency(PCE)of 24.74%and excellent operational stability.This study suggests that resonance structures can be an effective molecular design strategy for developing interfacial modifiers with both strong passivation capabilities and well-regulated charge dynamics.展开更多
[Objectives]To explore the synthetic process of PD-L1 small molecule inhibitors,focusing on optimizing key reaction conditions and synthetic routes.[Methods]By analyzing the pharmacophore design of PD-L1 small molecul...[Objectives]To explore the synthetic process of PD-L1 small molecule inhibitors,focusing on optimizing key reaction conditions and synthetic routes.[Methods]By analyzing the pharmacophore design of PD-L1 small molecule inhibitors and combining the optimization of synthetic methods and the improvement of reaction conditions,an efficient synthetic process was developed.[Results]Through optimization of reaction conditions,not only were the purity and yield of the products improved,but the inhibitory activity of the compounds was also significantly enhanced.Some compounds demonstrated strong anti-tumor effects in both in vitro and in vivo models.[Conclusions]This study aims to provide theoretical support and technical guidance for the efficient synthesis of small molecule inhibitors,offering new ideas and practical foundations for drug development in tumor immunotherapy.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82174010 and 81973512)。
文摘Stroke is the second leading cause of disability and mortality worldwide,imposing a substantial socioeconomic burden on individuals and healthcare systems.Annually,approximately 14 million people experience stroke,with ischemic stroke comprising nearly 85%of cases,of which 10%to 20%involve large vessel occlusions.Currently,recombinant tissue plasminogen activator(tPA)remains the only approved pharmacological intervention.However,its utility is limited due to a narrow therapeutic window and low recanalization rates,making it applicable to only a minority of patients.Therefore,there is an urgent need for novel therapeutic strategies,including pharmacological advancements and combinatory treatments.Small-molecule natural medicines,particularly those derived from traditional Chinese herbs,have demonstrated significant therapeutic potential in ischemic stroke management.These compounds exert multiple neuroprotective effects,such as antioxidation,anti-inflammatory action,and inhibition of apoptosis,all of which are critical in mitigating stroke-induced cerebral damage.This review comprehensively examines the pathophysiology of acute ischemic stroke(AIS)and highlights the recent progress in the development of small-molecule natural medicines as promising therapeutic agents for cerebral ischemic stroke.
基金National Natural Science Foundation of China:Study on the Molecular Mechanism of the Regulation of Crypt Goblet Cell Pyroptosis and Exocytosis to Repair Ulcerative Colitis Mucus Barrier by the Method of Clearing and Opening the Xuanfu from the Perspective of"Xuanfu-Crypt"(No.82305143),and National Natural Science Foundation of China:Exploring the Molecular Mechanism of"Hewei Jiangni Fang"Intervention in Non-erosive Reflux Disease Esophageal Hypersensitivity from the Perspective of Mas-related Gene X2/Stromal Interaction Molecule 1/Cell Adhesion Molecule 1 Pathway Regulation of Mast Cell/Dorsal Root Ganglion Communication based on the"Xinkai-Kujiang"Method(No.82374401)。
文摘OBJECTIVE:To explore if Hewei Jiangni granule(和胃降逆颗粒,HWJNG)could regulate esophageal hypersensitivity via stromal interaction molecule 1(STIM1)/transient receptor potential vanilloid subfamily member 1(TRPV1)pathway.METHODS:Qualitative analysis of HWJNG was analysis by high performance of liquid and gas chromatography.In vivo,animal model of non-erosive reflux disease(NERD)was established by fructose intake and restraint stress.HWJNG and Omeprazole were administered by gavage to the drug intervention group.Reflux and visceral hypersensitivity were analyzed by pathological changes,PH value test,mechanical paw withdrawal threshold,thermal withdrawal latency and mast cells(MCs)degranulation.In vitro,substance P(SP)-induced P815 cells and dorsal root ganglion(DRG)cells were cocultured.Expression in both mice and cells of STIM1,TRPV1,and esophageal visceral hypersensitivity-related gastrointestinal neurochemicals were validated by enzyme linked immunosorbent assays,quantitative realtime polymerase chain reaction(qRT-PCR)and Western blot.Moreover,overexpression and small interfering RNA against STIM1 were utilized to verify of the role of HWJNG in DRG cells.RESULTS:HWJNG significantly suppressed intercellular space widening,injury of mitochondrial,MCs degranulation,mechanical allodynia and heat neuropathic sensory and increased pH value of esophageal mucosa in NERD mice.HWJNG inhibited expression of visceral hypersensitivityrelated gastrointestinal neurochemicals in esophageal mucosa and activated P815 cells,and expression of the STIM1,TRPV1 and related neurotransmitters in DRG and DRG cells.STIM1 siRNA and HWJNG both reduced P815 cells adhesion to DRGs cells and Ca2+flow into the cytoplasmic space of DRG cells.Furthermore,HWJNG could reversed STIM1 overexpression induced upregulation of TRPV1.CONCLUSION:HWJNG suppressed intercellular space widening in NERD mice,stabilized MCs and restored neuronal hyperexcitability by regulating visceral hypersensitivity via STIM1/TRPV1 pathway.
文摘Acceptor-donor-acceptor(A-D-A)type molecules,of which the novel non-fused azacyclic end-group pyrazoli-nones were modified with chlorine substitution on the phenyl ring,were synthesized.The non-fused azacyclic end-group py-razolinones have the advantages of simple synthesis steps,low cost and environmental friendliness,compared to the classical end-group dicyanomethyleneindianone.The properties of the synthesized A-D-A type molecules with non-fused azacyclic end groups were characterized by theoretical calculation,UV-vis absorption,cyclic voltammetry,X-ray diffraction and space charge limited current.It is shown that the strong UV-vis absorptions of the synthesized A-D-A type molecules are located in the wavelength range of 500~700 nm,with a moderate band gap of nearly 1.7 eV.At the same time,the influence of end-group chlorination on the properties of A-D-A type molecules was compared and explored.It is proven that this kind of A-D-A type molecule with non-fused azacyclic end groups has the potential to be applied as interfacial modified layer of the active layer in perovskite solar cell devices.
文摘A tetranuclear Ln(Ⅲ)-based complex:[Dy_(4)(dbm)_(4)(L)_(6)(μ_(3)-OH)_(2)]·CH_(3)CN(1)(HL=5-[(4-methylbenzylidene)amino]quinolin-8-ol,Hdbm=dibenzoylmethane)was manufactured and its structure was characterized in detail.Xray diffraction analysis shows that complex 1 belongs to the monoclinic crystal system and its space group is P2_1/n,which contains a rhombic Dy_(4)core.Magnetic measurements of 1 suggest it possesses extraordinary single-molecule magnet(SMM)behavior.Its energy barrier U_(eff)/k_(B)was 116.7 K,and the pre-exponential coefficient τ_(0)=1.05×10~(-8)s.CCDC:2359322.
基金supported by NIH grants AG079264(to PHR)and AG071560(to APR)。
文摘The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration.Axons and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start networks.Here we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal cells.In this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)cDNA.To investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were used.Neurite outgrowth is evaluated through the segmentation and measurement of neural processes.These neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite growth.These neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal HT22.DDQ-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-tubulin.Additionally,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic outgrowth.Our findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara cteristics.The key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.
基金supported by the National Natural Science Foundation of China(No.22073090,No.21991132,No.52021002)the National Key R&D Program of China(No.2020YFA0710700)the Funds of Youth Innovation Promotion Association,and the Fundamental Research Funds for the Central Universities(WK3450000009).
文摘CRISPR-based tran-scription regulators(CRISPR-TRs)have revolutionized the field of synthetic biol-ogy by enabling tar-geted activation or repression of any de-sired gene.However,the majority of exist-ing inducible CRISPR-TRs are limited by their dependence on specific sequences,which restricts their flex-ibility and controllability in genetic engineering applications.In this study,we proposed a novel strategy to construct sequence-independent inducible CRISPR-TRs,which is achieved by the design of stem loop 2 in the single guide RNA(sgRNA).Under this strategy,by utiliz-ing toehold-mediated strand displacement(TMSD)reactions between small endogenous molecules(miR-20a and TK1 mRNA)and bridge RNA(bRNA)to link bRNA with sgRNA,we achieved synergistic transcriptional activation of VP64 and p65-HSF1 in response to en-dogenous molecules.To enable response to exogenous molecules,we added response se-quences and bRNA sequences to the 5'end of sgRNA to block sgRNA activity,and achieved activation of sgRNA by shearing the response sequence,called sequential unlimited interlock-ing(SUI).Compared with conventional sequence-restricted interlocking(spacer-blocking hairpin(SBH)),the transcriptional activation ratio between response and non-response to the Cas6A protein using our approach was increased by 2.28-fold.Our work presents a modular and versatile framework for endogenous and exogenous molecule-responsive CRISPR-TRs in mammalian cells,without limitations imposed by sequence dependence.
基金Project supported by the National Natural Science Foundation of China(Grant No.12164030)Young Science and Technology Talents of Inner Mongolia,China(Grant No.NJYT22101)+1 种基金the Central Government Guides Local Science,the Technology Development Fund Projects(Grant No.2023ZY0005)the Science and Technology Plan Projects of Inner Mongolia Autonomous Region of China(Grant No.2023KYPT0012)。
文摘In the last few years,research on advanced ultrafast photonic devices has attracted great interest from laser physicists.As a semiconductor material with excellent nonlinear saturation absorption characteristics,Ga As has been used in solidstate and fiber lasers as a mode-locker.However,the pulse widths that have been reported in the searchable published literature are all long and the shortest is tens of picoseconds.Femtosecond pulse widths,desired for a variety of applications,have not yet been reported in Ga As-based pulsed lasers.In this work,we further explore the nonlinear characteristics of Ga As that has been magnetron sputtered onto the surface of a tapered fiber and its application in the generation of femtosecond lasing via effective dispersion optimization and nonlinearity management.With the enhanced interaction between evanescent waves and Ga As nanosheets,mode-locked soliton pulses as short as 830 fs are generated at repetition rates of 4.64 MHz.As far as we know,this is the first time that femtosecond-level pulses have been generated with a Ga As-based saturable absorber.In addition,soliton molecules,including in the dual-pulse state,are also realized under stronger pumping.This work demonstrates that Ga As-based photonic devices have good application prospects in effective polymorphous ultrashort pulsed laser generation.
基金supported by Beijing Natural Science Foundation(Grant Nos.1252023 and QY24141)the Aeronautical Science Foundation of China(No.2024Z073051005)+1 种基金the State Key Laboratory of Advanced Optical Communication Systems and Networks,Chinathe National College Students Innovation and Entrepreneurship Training Program.
文摘Soliton molecules are fascinating phenomena in ultrafast lasers which have potential for increasing the capacity of fiber optic communication.The investigation of reliable materials will be of great benefit to the generation of soliton molecules.Herein,an all-fiber laser cavity was built incorporating carbon nanotubes-based saturable absorber.Mode-locked pulses were obtained at 1565.0 nm with a 60 dB SNR and a 4.5 W peak power.Soliton molecules were subsequently observed after increasing the pump power and tuning polarization state in the same cavity,showing variable separation of pulses between 4.87 and 25.76 ps.Furthermore,these tunable soliton molecules were verified and investigated through numerical simulation,where the tuning of pump power and polarization state were simulated.These results demonstrate that soliton molecules are promising to be applied in optical communication,where carbon nanotube-based mode-locked fiber lasers serve as a reliable platform for the generation of these soliton molecules.
基金supported in part by the National Natural Science Foundation of China(Grant Nos.62476247 and 62072409)the“Pioneer”and“Leading Goose”R&D Program of Zhejiang(Grant No.2024C01214)the Zhejiang Provincial Natural Science Foundation(Grant No.LR21F020003).
文摘The task of molecule generation guided by specific text descriptions has been proposed to generate molecules that match given text inputs.Mainstream methods typically use simplified molecular input line entry system(SMILES)to represent molecules and rely on diffusion models or autoregressive structures for modeling.However,the one-to-many mapping diversity when using SMILES to represent molecules causes existing methods to require complex model architectures and larger training datasets to improve performance,which affects the efficiency of model training and generation.In this paper,we propose a text-guided diverse-expression diffusion(TGDD)model for molecule generation.TGDD combines both SMILES and self-referencing embedded strings(SELFIES)into a novel diverse-expression molecular representation,enabling precise molecule mapping based on natural language.By leveraging this diverse-expression representation,TGDD simplifies the segmented diffusion generation process,achieving faster training and reduced memory consumption,while also exhibiting stronger alignment with natural language.TGDD outperforms both TGM-LDM and the autoregressive model MolT5-Base on most evaluation metrics.
基金supported by JSPS(No.22H00350 to M.U.)Ministry of Health&Welfare,Republic of Korea(Korea Health Technology R&D Project through the Korea Health Industry Development Institute,No.HI19C1234 to H.K.)+3 种基金JST(the Establishment of University Fellowships towards the Creation of Science Technology Innovation,No.JPMJFS2123 to K.T.)supported and inspired by the International Collaborative Research Program of Institute for Chemical Research,Kyoto University(No.2024-84)Kyoto University On-Site Lab(Fudan-Kyoto Shanghai Lab)the international and interdisciplinary environments of JSPS CORE-to-CORE Program“Asian Chemical Biology Initiative”.
文摘Biomolecular condensates,also known as membraneless organelles,play a crucial role in cellular organization by concentrating or sequestering biomolecules.Despite their importance,synthetically mimicking these organelles using non-peptidic small organic molecules has posed a significant challenge.The present study reports the discovery of D008,a self-assembling small molecule that sequesters a unique subset of RNA-binding proteins.Analysis and screening of a comprehensive collection of approximately 1 million compounds in the Chinese National Compound Library(Shanghai)identified 44 self-assembling small molecules in aqueous solutions.Subsequent screening of the focused library,coupled with proteome analysis,led to the discovery of D008 as a small organic molecule with the ability to condensate a specific subset of RNA-binding proteins.In vitro experiments demonstrated that the D008-induced sequestration of RNA-binding proteins impeded mRNA translation.D008 may offer a unique opportunity for studying the condensations of RNA-binding proteins and for developing an unprecedented class of small molecules that control gene expression.
基金Project supported by the National Natural Science Foundation of China (Grant Nos. 12174115,11834003,and 91836103)。
文摘The recently demonstrated methods for cooling and trapping diatomic molecules offer new possibilities for precision searches in fundamental physical theories.Here,we propose to study the variations of the fine-structure constant(α=e^(2)/(hc)) and the proton-to-electron mass ratio(μ=m_(p)/m_(e)) with time by taking advantage of the nearly degenerate rovibrational levels in the electronic states of the magnesium fluoride(MgF) molecule.Specifically,due to the cancellation between the fine-structure splitting and the rovibrational intervals in the different MgF natural isotopes,a degeneracy occurs for A^(2)П_(3/2)(v'=0,J'=18.5,-) and A^(2)П_(1/2)(v "=0,J" =20.5,-).We find that using the nearly degenerate energy level of such states can be 104 times more sensitive than using a pure rotational transition to measure the variations of α and μ.To quantify the small gap between A^(2)П_(3/2)(v'=0,J'=18.5,-) and A^(2)П_(1/2)(v "=0,J" =20.5,-),special transitions of choice are feasible:X^(2)Σ_(1/2)~+(v=0,J=19.5,+) to A^(2)П_(3/2)(v'=0,J'=18.5,-) and X^(2)Σ_(1/2)~+(v=0.J=19.5,+)to A^(2)П_(1/2)(v "=0,J" =20.5,-).In addition,we estimate the frequency uncertainties caused by the narrow linewidth,Zeeman shift,Stark shift,Doppler broadening and blackbody radiation.
基金Project supported by the National Natural Science Foundation of China (Grant Nos. 92250306 and 12304302)the Natural Science Foundation of Jilin Province, China (Grant Nos. YDZJ202101ZYTS157 and YDZJ202201ZYTS314)the Scientific Research Foundation of Jilin Province Education Department, China (Grant No. JJKH20230283KJ)。
文摘Molecular high-order harmonic spectroscopy is a significant advancement in ultrafast science, enabling the measurement of multielectron dynamics with attosecond temporal resolution. The fine structures observed in the molecular harmonic spectrum provide crucial insights into the structural or multielectron dynamical effects induced by intense laser fields. In this study, we measure the high-order harmonic spectrum of aligned CO_(2) molecules contributed from short trajectories. Two distinct groups of minima are identified in the plateau region. Our findings indicate that the deeper-lying molecular orbitals and two-center interference play significant roles in molecular harmonic generation. The results pave the way for advancing the understanding of multielectron dynamics in polyatomic molecules under intense laser fields.
基金supported by the National Natural Science Foundation of China(No.82173668,82373706).
文摘Immunotherapy has transformed cancer treatment,marked by the approval of numerous antibody-based drugs.However,the limitations of antibodies in pharmacokinetics including long half-lives,limited oral bioavailability and immunogenicity,have prompted the pursuit of small molecule-based immunotherapy.Traditional drug discovery strategies,which focus on blocking protein activity through inhibitors,face persistent hurdles,such as reliance on accessible binding pockets,poor selectivity,and the emergence of drug resistance.Targeted protein degradation(TPD)technologies have emerged as powerful tools to address these limitations,offering significant therapeutic advantages over conventional inhibition strategies,particularly for historically "undruggable" targets.In recent years,small molecule-based protein degraders have rapidly advanced in cancer immunotherapy.In this review,we highlight recent progress in TPD-driven small-molecule drug discovery and summarize the application of these technologies in cancer immunotherapy,including degraders targeting PD-1/PD-L1,chemokine receptors,IDO1,AhR,and others.
基金supported by the Young Elite Scientists Sponsorship Program by CAST(No.2023QNRC001)Natural Science Foundation of Hunan Province,China(No.2024JJ2074)supported in part by the High Performance Computing Center of Central South University,China and the Pawsey Supercomputing Centre with funding from the Australian Government and the Government of Western Australia.
文摘An in-depth understanding of the hydration mechanism of tricalcium silicate is an important basis for optimizing cement strength development.In this study,the adsorption of water molecules onto the M3-C3S(001)surface at different water coverage levels(θ=1/5,2/5,3/5,4/5,and 1)was investigated using first-principles calculations.The results demonstrate that the conclusions obtained for single water molecule adsorption cannot be fully applied to multiple water molecule adsorption.The total adsorption energies become more negative with increasing water coverage,while the average adsorption energy of each water molecule becomes more positive with increasing water coverage.The water–water interactions reduce the water–surface interactions and are responsible for the anticooperative adsorption of multiple water molecules onto M3-C_(3)S(001).The formation of Ca–OH(–Ca)bonds favors the detachment of Ca from co-valent oxygen,which reveals the significant role of dissociative adsorption.This work aims to extend the water adsorption study on M3-C3S(001)from single water molecule adsorption to multiple water molecule adsorption,providing more detailed insights into the initial water reaction on the C3S surface.
基金supported by the National Natural Science Foundation of China(Nos.22077044 and 21672080)the Natural Science Foundation of Hubei Province(No.2022CFA033)the funding from Wuhan Institute of Photochemistry and Technology(No.GHY2023KF008).
文摘Cancer is a serious global health issue,and exploring effective treatment methods is of great significance for cancer prevention and control.Carbon monoxide(CO),as an important gas signaling molecule in the life system,has been proven to have good anti-cancer effects.However,how to controllably,safely,and effectively deliver CO to the tumor site for clinical treatment remains a challenge.Herein,a new metal-free CO-releasing molecule COR-XAC was developed for controlling CO release and cancer therapy.COR-XAC is based on the hybrid of 3-hydroxyl flavone and oxanthracene fluorophores,showing visible light-controlled CO-releasing properties and near-infrared(NIR)ratiometric fluorescence changes at 690 and 760 nm.COR-XAC shows low cytotoxicity and can be successfully applied to release CO in cells and tumors,and the CO-releasing and delivery process could be monitored by its own NIR ratiometric fluorescence changes.More importantly,the anti-cancer performance of COR-XAC was evaluated in 4T1 tumor mice,and it was found that COR-XAC plus light illumination showed excellent tumor inhibition effect,which provided a promising new effective method for cancer treatment.
基金supported by the National Natural Science Foundation of China under Grant Nos.92265209,11174081 and 62305285the Natural Science Foundation of Chongqing under Grant No.CSTB2024NSCQ-MSX0643the Shanghai Municipal Science and Technology Major Project under Grant No.2019SHZDZX01。
文摘Quantum algorithms offer more enhanced computational efficiency in comparison to their classical counterparts when solving specific tasks.In this study,we implement the quantum permutation algorithm utilizing a polar molecule within an external electric field.The selection of the molecular qutrit involves the utilization of field-dressed states generated through the pendular modes of SrO.Through the application of multi-target optimal control theory,we strategically design microwave pulses to execute logical operations,including Fourier transform,oracle U_(f)operation,and inverse Fourier transform within a three-level molecular qutrit structure.The observed high fidelity of our outcomes is intricately linked to the concept of the quantum speed limit,which quantifies the maximum speed of quantum state manipulation.Subsequently,we design the optimized pulse sequence to successfully simulate the quantum permutation algorithm on a single SrO molecule,achieving remarkable fidelity.Consequently,a quantum circuit comprising a single qutrit suffices to determine permutation parity with just a single function evaluation.Therefore,our results indicate that the optimal control theory can be well applied to the quantum computation of polar molecular systems.
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.
基金supported by the Research Grants Council of the Hong Kong Special Administrative Region of China(Grant Nos.HKU 17212824,HKU 17210522,HKU C7074-21G,HKU R7003-21,and HKU 17205321)the Innovation and Technology Commission of the Hong Kong SAR Government(Grant Nos.MHP/073/20 and MHP/057/21),and the Health@InnoHK program.
文摘Soliton molecules(SMs),bounded and self-assembled of particle-like dissipative solitons,exist with versatile mutual interactions and manifest substantial potential in soliton communication and optical data storage.However,controllable manipulation of the bounded molecular patterns remains challenging,as reaching a specific operation regime in lasers generally involves adjusting multiple control parameters in connection with a wide range of accessible pulse dynamics.An evolutionary algorithm is implemented for intelligent control of SMs in a 2μm ultrafast fiber laser mode locked through nonlinear polarization rotation.Depending on the specifications of the merit function used for the optimization procedure,various SM operations are obtained,including spectra shape programming and controllable deterministic switching of doublet and triplet SMs operating in stationary or pulsation states with reconfigurable temporal separations,frequency locking of pulsation SMs,doublet and SM complexes with controllable pulsation ratio,etc.Digital encoding is further demonstrated in this platform by employing the self-assembled characteristics of SMs.Our work opens up an avenue for active SM control beyond conventional telecom bands and brings useful insights into nonlinear science and applications.
基金the financial support from the Natural Science Foundation of Xiamen,China(3502Z202373075)the National Natural Science Foundation of China(Grant nos.22175180,52311530673,22103013)+1 种基金the Natural Science Foundation of Fujian Province(No.2023J01527,2021J01184,2024J01189)the Start-up funding from Fujian Normal University(Y0720312K13)。
文摘Exploring multifunctional interfacial modifiers is an effective approach to addressing interface issues in perovskite solar cells(PSCs)and improving device performance and stability.While most interfacial modifiers focus on passivating defects at the interfaces,there has been limited investigation into the relationship between molecular design and interfacial charge dynamics.This work introduces resonance molecules with a push-pull effect for interfacial modification,allowing for synergistic regulation of passivation effects and charge dynamics.Specifically,FCz-PO,which includes an electron-withdrawing fluorine atom,exhibits superior passivation but poor molecular stacking and charge extraction.In contrast,MCz-PO,featuring an electron-donating methoxy group,provides effective passivation,wellordered molecular packing,and efficient charge extraction and transport.Consequently,PSCs using MCz-PO achieve high power conversion efficiency(PCE)of 24.74%and excellent operational stability.This study suggests that resonance structures can be an effective molecular design strategy for developing interfacial modifiers with both strong passivation capabilities and well-regulated charge dynamics.
文摘[Objectives]To explore the synthetic process of PD-L1 small molecule inhibitors,focusing on optimizing key reaction conditions and synthetic routes.[Methods]By analyzing the pharmacophore design of PD-L1 small molecule inhibitors and combining the optimization of synthetic methods and the improvement of reaction conditions,an efficient synthetic process was developed.[Results]Through optimization of reaction conditions,not only were the purity and yield of the products improved,but the inhibitory activity of the compounds was also significantly enhanced.Some compounds demonstrated strong anti-tumor effects in both in vitro and in vivo models.[Conclusions]This study aims to provide theoretical support and technical guidance for the efficient synthesis of small molecule inhibitors,offering new ideas and practical foundations for drug development in tumor immunotherapy.
