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    Disciplines / Research questions

    医学

    55 个研究主题 · 216 个问题

    睡眠阻塞性疾病成因、发病机制及诊治研究3 个问题

    1. A validated, operational, multi-domain definition of surgical success and failure in adult obstructive sleep apnea surgery

    2. Translating PALM phenotypic-cause characterization of obstructive sleep apnea into routine clinical measurement and mechanism-targeted therapy (unresolved issues identified by Eckert et al., 2013)

    3. Definitive randomized evaluation of drug-induced sleep endoscopy–directed treatment planning in children with conventional obstructive sleep apnea–hypopnea syndrome

    糖尿病微血管并发症的早期干预3 个问题

    1. Can early diabetic retinal neurodysfunction, measured by multifocal ERG implicit-time delays, be causally validated and therapeutically modified to prevent vascular diabetic retinopathy?

    2. Mechanism of the glycemic legacy effect (metabolic memory) after early intensive glucose control in type 2 diabetes

    3. Determinants of renal failure in type 2 diabetes beyond hypertension and hyperglycemia: the nonalbuminuric pathway

    天然免疫与获得性免疫分工合作、互相调控的基础是什么4 个问题

    1. Molecular mechanism of the hypothalamus–fat axis linking innate TNF signaling to rapid peripheral T- and B-cell expansion, and its failure in obesity

    2. Determinants of antibody-mediated compensation versus inflammatory disease after innate immune lesions in host-microbiota mutualism

    3. Division of labor between innate lymphoid cells and adaptive T helper cells in GM-CSF-mediated mucosal protection during intestinal inflammation in Crohn's disease

    4. Mechanisms by which adaptive immunity restrains tonic ILC-derived IFN-γ and type 1 polarization of innate lymphoid cells during intestinal homeostasis

    天然无结构的蛋白质的机制7 个问题

    1. Generalizing localized versus distributed interactions in disordered-protein phase separation: a general sequence-to-threshold mapping beyond minimal two-letter models

    2. General mechanism of coupled folding and binding of intrinsically disordered proteins: mapping and predicting encounter-complex-mediated folding versus conformational selection across IDP–partner systems

    3. Coupled binding and folding of intrinsically disordered proteins: quantitative atomistic kinetics and the mechanism of rapid folding-upon-binding in the NCBD/ACTR pair

    4. Cellular mechanism of complex coacervation by the nephrin intracellular domain: endogenous polycationic partners and the structural nature of dense-phase adhesions

    5. General applicability of the disordered binding mechanism of small-molecule stabilisation of intrinsically disordered proteins, and experimental validation of its predicted kinetics

    6. Whether and how soft disorder regions contribute to human disease through disruption of disorder-mediated interactions

    7. Functional mechanism of the intrinsically disordered N-terminal region of Mycobacterium tuberculosis ChiZ in cell division

    微小RNA表达调控规律、网络及其生物学意义3 个问题

    1. In vivo prevalence and quantitative significance of miRNA/ceRNA crosstalk at the protein level

    2. Do endogenous competing RNAs reach miRNA derepression thresholds in vivo: physiological prevalence of competition-based ceRNA regulation and its locus-specific genetic test

    3. Mechanism and physiological scope of target mRNA-driven biogenesis of cognate microRNAs in human cells

    为何研制HIV等疫苗迄今难以成功6 个问题

    1. Maturation of eOD-GT8-primed VRC01-class broadly neutralizing antibody precursors to broad neutralization of native HIV-1 by sequential booster immunization in humans

    2. Determinants of HIV-1 broadly neutralizing antibody induction: unresolved host-population, subtype-structural, and exposure-dependence components

    3. Prospective test of whether focusing CD8+ T cell responses on highly networked HIV epitopes confers protection

    4. Eliciting heterologous Tier-2 neutralization breadth in humans with native-like HIV-1 envelope SOSIP.664 trimers: immunogen redesign, regimen design, and the fate of autologous responses

    5. After the mosaic Ad26 HIV-1 vaccine efficacy failures: mechanistic immune correlates of protection in humans, predictive validity of the rhesus SHIV challenge model, and elicitation of tier-2 broadly neutralizing antibodies

    6. Human translation of N332-GT germline-targeting sequential vaccination to induce BG18-class broadly neutralizing antibodies against HIV-1

    细胞中的染色体如何维持自己的特性2 个问题

    1. How is centromere identity established de novo and inherited across generations in the Caenorhabditis elegans maternal germ line?

    2. Mechanism and generality of active CENP-A centromere maintenance in quiescent cells

    小分子化合物的药效活性预测2 个问题

    1. Making QSAR models activity-cliff-aware: pair-based training, representations beyond fingerprints, generalisable error–cliff coupling, and prospective validation of activity-cliff prediction

    2. Closing the multimodal fusion gap in compound activity prediction from chemical structure, Cell Painting morphology, and L1000 transcriptomics

    炎性复合体是如何活化并在炎性疾病中发挥作用的4 个问题

    1. Cardiolipin-mediated NLRP3 inflammasome activation: the molecular mechanism of the cardiolipin-NLRP3 interaction, its cooperation with mitochondrial DNA, and the decision between inflammasome activation and apoptosis

    2. Molecular mechanism by which 2′3′-cGAMP activates the AIM2/NLRP3 inflammasome: the activation-step role of STING, direct cGAMP–inflammasome interactions, and AIM2–NLRP3 cooperation within a single inflammasome focus

    3. Causal contribution of TNF-α–mediated NLRP3 inflammasome activation to psoriasis-associated systemic inflammation and cardiovascular comorbidity in vivo

    4. Mechanism of K+^+-efflux-independent NLRP3 inflammasome activation by imidazoquinolines (imiquimod/CL097): the complete cellular target set, the triggering combination of biochemical consequences, and the relay from ROS to NLRP3 assembly

    炎症性肠病的发病机制和生物治疗的研究3 个问题

    1. Prospective validation of therapeutic drug monitoring–guided clinical decision making at secondary loss of response to biologic therapy in inflammatory bowel disease

    2. Mechanism and Translational Significance of Biological-Therapy-Induced Restoration of the Intestinal Innate Lymphoid Cell Subset Equilibrium in Inflammatory Bowel Disease

    3. Genetic and microbial modulation of the ubiquitin–proteasome system in inflammatory bowel disease: causal alleles at the CYLD–NOD2 and USP-family loci, the molecular mechanism of AIEC-driven proteasome modulation, and its pathophysiological and therapeutic validation

    疫苗有效抗原成分的选择2 个问题

    1. Validating and developability-prioritizing the positive-unlabeled-learning-predicted vaccine candidate antigens of Plasmodium falciparum

    2. Unresolved development path for CASS-identified Neisseria gonorrhoeae vaccine antigens: efficacy beyond mouse colonization, candidate characterization, population coverage, commensal safety, formulation, and human correlates of protection

    疫苗佐剂研发中的挑战4 个问题

    1. Mechanism and Th1 reprogramming of pristine mesoporous carbon hollow-sphere vaccine adjuvants

    2. Mechanism and protective value of MF59 adjuvant-driven enhancement of anti-hemagglutinin antibody affinity and epitope breadth in influenza vaccination

    3. Whether parenteral SLA-SE adjuvantation elicits functional mucosal antibodies in humans: the unresolved translational questions from a mouse ETEC vaccine study

    4. Validated, internationally accepted safety-evaluation framework for vaccine adjuvants: separating immunostimulation from toxic reactogenicity, establishing cross-species extrapolation, and building a shared safety evidence base

    针灸效应的规律及机制2 个问题

    1. Frequency-dependent mechanisms of electroacupuncture analgesia in neuropathic pain: causal validation of the serotonergic hypothesis for kilohertz (18 kHz) stimulation, frequency generalization, and long-term durability

    2. The upstream mechanism by which mechanical stimulation at a distal acupoint remotely induces mTOR-independent autophagic clearance of aggregation-prone proteins in the brain

    肿瘤干细胞与多药耐药3 个问题

    1. Selection versus inducible regulation: the molecular basis of post-chemotherapy MDR1/BCRP elevation in surviving breast cancer stem cells and its therapeutic interception

    2. Origin and therapeutic exploitation of MDR1-dependent chemoresistance in MYC-driven hepatic cancer stem cells

    3. Does Oct-4/POU5F1 directly drive the ABC-transporter multidrug-resistance program of chronic myeloid leukemia cells?

    重要病毒入侵的分子机制5 个问题

    1. Mapping the cholesterol-dependent hemifusion pathway switch of influenza virus entry onto the native late endosomal membrane

    2. Cellular Entry Receptors and Post-Entry Determinants of Broad Host Tropism in Flaviviruses

    3. Atomic structure of the paramyxovirus F–attachment protein (HN/H/G) triggering complex and the receptor-induced conformational cascade linking receptor binding to stalk exposure and F activation

    4. Coreceptor-triggered conformational transitions of the HIV-1 envelope glycoprotein trimer beyond the CD4-bound state: mechanism, stoichiometry, and geometry of CCR5/CXCR4 engagement

    5. Activation mechanism of the herpesvirus fusion glycoprotein B: the cellular trigger and its allosteric coupling to the domain V helix switch

    重要中药及天然药用生物资源活性成分的生物合成及其关键酶系统2 个问题

    1. The plant sterol side-chain-cleaving enzyme (P450scc) of cardenolide biosynthesis: catalytic mechanism, canonical CYP87A paralog functions, and identification in remaining lineages

    2. Unresolved biology of the morphinan O-demethylases T6ODM and CODM in opium poppy: in-planta roles of promiscuous demethylations, indirect acylcyclohexanedione action, the top1 lesion, structural basis of regioselectivity, and evolutionary origin

    子痫前期的发病机制3 个问题

    1. Mechanisms of divergent trophoblast invasion and apoptosis in placental bed spiral arteries: why is remodeling failed in early-onset preeclampsia/IUGR but enhanced in maternal anemia?

    2. Temporal hemodynamic origins of early and late preeclampsia: subtype trajectories before 24 weeks, the causal role of maternal body mass index, and postpartum cardiovascular consequences

    3. Open mechanistic core of the macrophage-orchestrated placental immune network in preeclampsia: how pro-inflammatory macrophages suppress granulocytic MDSCs, and the fetal antigen specificity of memory-like Th17 cells in recurrence

    组织工程、组织/器官生物学培养、原位再生，哪条道能捷足先登6 个问题

    1. Open barriers to a transplantable bioengineered liver from decellularized whole-liver scaffolds: complete endothelialization, non-thrombogenic perfusion, and clinical-scale recellularization

    2. Origin, temporal control, and immunovascular mechanisms of endogenous MSC recruitment by SDF-1α-loaded bone-regeneration scaffolds

    3. Long-term perfusion, circulatory connection, and vascular maturation of in vitro-generated human organoid vascular networks

    4. Generating a bioartificial heart with physiological conduction and pump function by whole-heart recellularization

    5. Host-neovascularization-driven maturation of transplanted human cardiac organoids: adult-equivalent contractile function and angiocrine mechanisms

    6. Functional maturation of human pluripotent stem cell-derived kidney organoids: sustained nephrogenesis and quantitative benchmarking against native human kidney

    HIV、流感病毒等是如何逃避免疫监控的8 个问题

    1. Mechanisms by which the latent HIV-1 reservoir persists under CD8+ T-cell surveillance, and the T-cell breadth and tissue trafficking required to prevent escape upon viral rebound

    2. Quantitative rules of viral glycan-shield immune evasion: how glycan occupancy, glycoform heterogeneity, and dynamics determine shield completeness and neutralization breadth, and whether the crowded-versus-dispersed glycan taxonomy generalizes beyond HIV-1 Env

    3. Context-dependent role of HIV-1 Env position 276 and its N-linked glycan in neutralization by CD4-binding-site broadly neutralizing antibodies

    4. Determinants and predictive value of immune-escape-driven glycan remodeling for broadly neutralizing antibody elicitation at HIV-1 envelope glycan-dependent epitopes

    5. Long-term evolutionary dynamics of waning-immunity-driven antigenic escape in respiratory viruses

    6. HIV-1 escape from combined V3-glycan broadly neutralizing antibody and host autologous antibody pressure: glycan-shift routes, fitness costs, and protective correlates for immunotherapy

    7. Differential antibody recognition and immune-driven evolution of the HIV-1 envelope V3-base GDIR–glycan site

    8. Therapeutic T-cell vaccination for durable post-ART control of HIV-1: overcoming archived escape variants, CD8+ breadth limits, and follicular-site trafficking barriers

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