The inherent factors influencing the growth of lithium (Li) dendrites and the kinetics of Li + migration in polymer electrolytes lie in the electron cloud density distribution in the electrolyte. Localized electrons accumulation can trigger the uneven Li + deposition, ultimately leading to battery failure. To address this critical challenge, the concept of p–π conjugation and B–O sp 2 hybridization is innovatively incorporated into covalent organic frameworks (COFs) to mitigate local interfacial Li + accumulation and improve Li + migration kinetics in electrolytes by electron delocalization. Furthermore, perfluoroalkyl group with virtues of superior electron regulating capabilities and improved electrochemical‐window, is strategically grafted to better match high‐voltage cathodes. Under the synergistic role of electron regulation, the electrolyte with pπ–sp 2 ‐COF significantly improves overall electrochemical performance of solid‐state batteries. Thus, regulating electron density via p‐π conjugation and B‐O sp 2 hybridization promises to open new avenues for the development of COFs‐modified polymer electrolytes in solid‐state batteries.

In the present study, by building on the previous development of a DC-SIGN-targeting virus-like structure (VLS) vaccine platform and a comprehensive characterization of SARS-CoV-2 structural biology, particularly insights into the role of the nucleocapsid (N) protein in eliciting cytotoxic T lymphocyte (CTL) responses during infection, we designed a SARS-CoV-2 virion-mimetic structural vaccine that encapsulates an mRNA encoding the spike S1 antigen complexed with N protein complexes, with S1 proteins loaded on its surface. This characterized virion-mimetic structural vaccine not only induces the production of high-efficiency antibodies against both the spike and N proteins but also elicits robust S1-specific and N-specific CTL responses in animal models. Furthermore, the generated antibodies exhibit cross-reactive neutralizing activity against multiple SARS-CoV-2 variants and provide protective immunity against challenge with mutant viruses in immunized hosts. This SARS-CoV-2 virion-mimetic structure effectively recapitulates natural infection pathways, comprehensively activating the innate immune system and thereby creating an optimal microenvironment for eliciting potent and broad-spectrum adaptive immune responses.

Sepsis is a leading cause of mortality among patients in intensive care units (ICUs), with no specific treatments for sepsis available in clinical practice. In this study, we report the discovery of compound A12, a tanshinone derivative featuring a covalent warhead, which demonstrates potent anti-inflammatory effects both in vitro and in vivo. In a lipopolysaccharide-induced mouse model of endotoxemia and acute systemic inflammation, A12 significantly reduces levels of TNF-α, IL-6, and IL-12. Distinct from current anti-inflammatory small molecules, A12 presents a unique mechanism, covalently binding to DNAJC9, thereby modulating the HSP complex and inhibiting the downstream inflammatory response. This work represents the first application of covalent drug design principles to the structural modification of the natural product tanshinone, and reveals the previously unrecognized role of DNAJC9 in inflammatory diseases, offering a novel therapeutic target for management of sepsis-associated acute systemic inflammation.

How to efficiently explore chemical space to discover new compounds remains an important challenge in drug discovery. In this work, we introduce a Transformation strategy that enables efficient, scaffold-guided exploration of sub-chemical space around known bioactive molecules to obtain broad-spectrum inhibitors capable of targeting multiple proteins with related binding pockets. The core concept is to retain a validated binding scaffold responsible for essential target interactions, while systematically modifying peripheral regions to rapidly access nearby chemical space associated with target variability and functional optimization. We applied this strategy to the 3C-like protease (3CLpro), a conserved enzyme present in multiple coronaviruses and a key target for broad-spectrum antiviral development. Key pharmacophoric features of the SARS-CoV-2 3CLpro inhibitor Leritrelvir were preserved as the core scaffold to maintain critical active-site interactions, while non-essential regions were iteratively transformed within a defined sub-chemical space to generate structurally diverse analogues. Using this, several novel compounds were designed, synthesized and evaluated. Compounds 7c and 7d exhibited potent inhibition of SARS-CoV-2 3CLpro. Notably, compound 7c showed broad-spectrum antiviral activity, maintaining potency comparable to Leritrelvir against β-coronavirus 3CLpro, while demonstrating improved inhibition against α-coronavirus HCoV-NL63 3CLpro. Its anti-SARS-CoV-2 activity was essentially equivalent to Leritrelvir, while its anti-HCoV-NL63 activity was superior. Overall, these results demonstrate that the Transformation strategy is an effective and generalizable framework for scaffold-guided chemical space exploration, particularly suitable for multi-target systems such as viral proteases, where conserved scaffolds maintain baseline activity, while sub-chemical space exploration enables optimization of potency, spectrum coverage, and resistance mitigation.

As one type of promising material, porous organic polymers (POPs) have been widely used in sodium-ion battery (SIB) electrodes on account of their environmental friendliness and adjustable pore diameter. However, their capacity and rate performance require further improvement. Herein, a conjugated porous polymer (PQ-POP), containing an azaacene-deficient electron-deficient system, was synthesized by a simple condensation reaction. The conjugated and N-containing heteroaromatic structure improves the conductivity, charge-transfer efficiency, and physicochemical stability. Also, the porous polymeric framework shows a large specific surface area and high porosity, providing a large contact area with electrolytes and reducing the diffusion distance. Therefore, PQ-POP exhibits very good electrochemical properties. Besides its superior reversible specific capacity of 245 mAh g-1, PQ-POP also shows remarkable cycling stability, maintaining almost 100% after 1000 cycles at 4 A g-1. At 10 A g-1, its capacity holds steady at 202 mAh g-1, outperforming many similar materials. The sodium ion storage mechanism of PQ-POP was confirmed by in situ FTIR and XPS experiments. In order to broaden the application of PQ-POP in SIBs, the electrochemical performance of PQ-POP as the negative electrode and Na3V2(PO4)3 as the positive electrode were employed to assemble a full cell, where, even at 3 A g-1, the full cell based on PQ-POP//Na3V2(PO4)3 maintained 101 mAh g-1 of the capacity with nearly 100% coulomb efficiency, highlighting its potential in energy storage applications and providing perspectives into designing advanced POP electrodes for SIBs.

Schistosomiasis remains a major public health concern in Africa, despite global efforts to eliminate the disease by 2030. This study estimates the burden, trends, and inequalities of schistosomiasis in Africa from 1990 to 2021, and projects future prevalence to inform the WHO’s elimination strategies. Data from the Global Burden of Disease Study (GBD 2021) were used to calculate annual average percentage change (AAPC) and annual percentage change (APC), with spatial global autocorrelation analysis performed to examine temporal and spatial trends. Five modeling algorithms were constructed to predict disease burden in Africa from 2022 to 2041. The age-standardized prevalences rate (ASPR) of schistosomiasis in Africa decreased from 18,495.51 per 100,000 in 1990 to 9,461.76 per 100,000 in 2021. The total number of cases, disability-adjusted life-years (DALYs), and mortality accounted for 84.25%, 87.92% and 87.28% of the global totals, respectively. ARIMA modeling predicts that by 2030, the ASPR will reach 3.99%. Despite progress, the burden remains significant, and intensified efforts are needed, particularly in high-burden regions like West Africa, to meet the WHO’s 2030 elimination targets.

Solid‐state lithium batteries have attracted significant interest due to their potential to enhance the safety and energy density of modern energy storage systems. However, challenges such as low ionic conductivity and poor interfacial compatibility have hindered their widespread adoption. In this study, a novel hydrogen‐bonded organic framework (HOF) composite polymer electrolyte (HCPG@SPE) is developed by integrating trimesic acid and melamine‐based HOFs with a natural polymer matrix composed of gelatin and chitosan. The hydrogen‐bonding interactions between the matrix and HOF in HCPG@SPE impart remarkable mechanical strength and thermal stability. Additionally, due to the weak interactions between HOF and lithium‐ions, and its anion adsorption capacity, HCPG@SPE effectively generates more free lithium‐ions, facilitating their migration while inhibiting anion movement. Electrochemical tests revealed that HCPG@SPE exhibited high ionic conductivity (5.74 × 10⁻ 3 S cm⁻¹ at 30 °C), a favorable lithium‐ion transference number (0.71), and an extended electrochemical stability window (5.4 V). Additionally, lithium metal batteries utilizing this electrolyte achieved outstanding performance, with LFP| HCPG@SPE| Li cells retaining 98% capacity after 1000 cycles at 5 C, and NCM811| HCPG@SPE| Li cells demonstrating stable cycling for 700 cycles at 1 C. The results suggest that the HOF‐based composite electrolyte holds significant promise for next‐generation high‐performance solid‐state lithium batteries.

Lithium metal is regarded as an ideal anode material for high-energy-density batteries due to its high theoretical capacity and low electrochemical potential. However, its practical application is hindered by unstable electrode-electrolyte interfaces and lithium dendrite growth. Covalent organic frameworks (COFs), with ordered ion transport channels and abundant lithiophilic sites, offer a promising solution by facilitating uniform lithium deposition, suppressing dendrites, and mitigating side reactions. This review presents a comprehensive overview of the application of COFs in various battery components for regulating interfacial chemistry and inhibiting dendrite growth. The design concepts and synthesis techniques of COFs are explained in detail, and the discussion of present issues and potential future research avenues is included in the end.

BACKGROUND:Previous studies have highlighted the critical role of the Yes associated protein 1 - TEA domain transcription factor (YAP1-TEAD) interaction in the progression of oral cancer. However, there remains a lack of direct disruptors targeting the YAP1-TEAD protein interaction and a detailed investigation of their effects on oral cancer. Therefore, we aimed to rationally design peptide YAP1-TEAD protein interaction disruptors through computational methods and explore the effects of direct disruption of the YAP1-TEAD interaction in oral squamous cell carcinoma (OSCC). METHODS:Peptide-based computational residue scanning was employed to design peptide disruptors of YAP1-TEAD interaction by analyzing the effects of mutations on binding affinity and stability. Molecular dynamics (MD) simulations were performed to assess the binding affinity and stability from a dynamic perspective. Surface plasmon resonance (SPR) assays were used to assess the in vitro binding affinities. After three rounds of iterative optimization, two with the highest affinities of this series of disruptors were applied to OSCC cell lines to investigate the primary effects of direct disruption of the YAP1-TEAD interaction. RESULTS:The expression of YAP1, TEADs, and four downstream transcriptional targets were significantly higher in OSCC tissues compared to paired normal tissues. The design and evaluation of YAP1-TEAD disruptors were conducted using computational residue scanning, MD simulations, and SPR assays. After three rounds of optimization, YTPD9 and YTPD11 demonstrated the highest affinities, with binding affinities 10 times more than that of the wildtype YAP1. When applied to OSCC cell lines, the disruptors exhibited a limited effect on cell proliferation, but they were able to inhibit the abilities of migration and invasion effectively. CONCLUSION:This study developed a series of peptide disruptors targeting YAP1-TEAD protein interaction through computational simulations and in vitro experiments. The biological evaluation of two of these disruptors in OSCC confirmed that direct disruption of the YAP1-TEAD primarily affects the migration and invasion ability of oral cancer.

Introduction: Strategic investment in new interventions is crucial for controlling and eliminating NTDs. However, selecting the optimal intervention combination is challenging, especially with limited resources and urgent disease transmission. Hybrid models offer a flexible framework for simulating intervention scenarios, but their use in NTDs control remains underexplored. Objectives: To propose a novel One Health-driven framework to guide and accelerate the elimination of NTDs. Methods: The proposed simulation framework consists of three parts: the disease dynamics model (the white box), the emulation process (the black box with supervised machine learning methods), and their joint contribution to optimizing the intervention strategy (the grey box). We demonstrate how this optimized strategy supports the development of new disease intervention tools using clonorchiasis as an example. Results: The comparison of several simulators consistently indicated that Gaussian process is the best machine learning core function. A disease model emulator with high-precision prediction ability was developed through extensive training. Optimizing intervention measures showed that chemotherapy was most effective, but long-term repeated chemotherapy carries the risk of drug resistance and economic burden. Fish vaccination addresses this contradiction. After five years of application, fish vaccination alone (99% efficacy) reduced prevalence by 34.16%, while the combination of chemotherapy and fish vaccination reduced it by 86.24%. The combination of chemotherapy and fish vaccination, both with 85.74% coverage, achieved all health goals in six scenarios. Conclusions: In resource-limited settings, eliminating clonorchiasis requires quantitative consideration of intervention strategies and cost-effectiveness. The combination of chemotherapy and fish vaccination has shown long-term benefits and is expected to help eliminate the disease. This innovative framework provides a theoretical basis and technological pipeline for research and development (R&D) investment, as well as the development of new intervention measures and/or products in countries with limited resources.

The rapid evolution of molecular representation methods has significantly advanced the drug discovery process. Advances in language models, graph-based representations, and novel learning strategies have greatly improved the ability to characterize molecules. These AI-driven strategies extend beyond traditional structural data, facilitating exploration of broader chemical spaces and accelerating scaffold hopping. This review summarizes key advancements, discusses their advantages over conventional techniques, and highlights challenges in data quality and real-world applications.

Metal ions play essential roles in living cells, yet their biological functions, which depend on intracellular concentrations, are not fully understood. Therefore, there is a critical need for efficient and sensitive methods to monitor metal ion levels in biological systems. Herein, we report the development of a fluorescent probe, 2-hydroxy-1-naphthaldehyde-(dithiophen-2-yl)ethanediamine (NS), for the precise and sensitive detection of intracellular Al3+ at concentrations as low as 3.92 × 10-8 M. The probe features a bifunctional thienyl ethanol ligand, consisting of two thiophene rings and a hydroxyl group, which forms stable coordination with Al3+. This interaction modifies the electron allocation within the ligand, suppressing the excited-state intramolecular proton transfer (ESIPT) mechanism and significantly increasing fluorescence intensity. Notably, in the presence of Al3+, compared to other ions, the fluorescence intensity of NS at 452 nm increases by 77-fold, with an exceptional sensitivity and selectivity for Al3+. Furthermore, the hydroxyl group enhances the probe's solubility and stability in aqueous solutions, making it highly effective for intracellular detection of Al3+ in prostate cancer RM-1 cells. The response mechanism is further investigated through 1H NMR and DFT studies, revealing the contributions of ESIPT, photoinduced electron transfer (PET), and CN isomerization to the probe's fluorescence behavior. This work provides a promising and advanced tool for ionobiology, opening new avenues for research into metal ion-related biological processes.

Low yields and quality defects in bayberry cultivation are primarily attributed to insufficient pollen supply and barriers to cross-pollination. To overcome the breeding bottleneck, this study focuses on the technology of chemically inducing male flower differentiation in female plants to establish a controllable pollen source system. Based on the previously observed phenomenon of female flower sex conversion, a systematic screening of chemical induction protocols for yingsi bayberry spring shoots was conducted. The results indicate that spraying uniconazole during the critical period of flower bud physiological differentiation (October–November) significantly induces the formation of functional male flowers in female plants, with pollen viability reaching 89.3 ± 2.1

Background: Oncomelania hupensis (O. hupensis), the unique intermediate host for Schistosoma japonicum, exerts a substantial influence on the risk of schistosomiasis. Being amphibious freshwater snails, the growth, development, and reproductive distribution of O. hupensis are intricately tied to climatic environmental variables. This study aims to predict O. hupensis habitat risks along the Yangtze River in China, considering multiple environmental factors. Methods: Data pertaining to the distribution of O. hupensis, including both presence and absence records, with the Jiangsu section of the Yangtze River basin for the period 2017-2021, were retrieved from the Jiangsu Schistosomiasis Control Information Platform. Ten machine learning algorithms and an ensemble model were used to explore environmental drivers. Three datasets (Snail_CLIM, Snail_TOPO, and Snail_ALL) incorporating climatic and topographic variables were examined for their impact on model accuracy. We conducted validation using the AUC and TSS metrics. Moreover, we utilized the data from the 2022 snail field survey for model external validation. Results: The findings demonstrate that snail_ALL, which incorporates both climatic and topographic variables, exhibits superior performance (ensemble model: sensitivity = 98.000, specificity = 95.960, AUC = 0.994). Among the ten model algorithms, Random Forest (RF) exhibited the highest degree of accuracy and stability (Snail_ALL: AUC = 1.000 +/- 0.000, TSS = 0.985 +/- 0.005). The key environmental factors affecting snail distribution included the distance to the nearest river, elevation, annual precipitation, and annual average pressure. High-risk areas manifested as two distinct concentrations: downstream of the Luhe District in Nanjing and at the confluence of Zhenjiang and Yangzhou. The results of 2022 field validation showed that over 90 % of the data points for snail breeding sites are concentrated in medium to high-risk areas. Conclusion: By selecting pertinent environmental variables and employing ensemble modeling techniques, we can accurately predict O. hupensis habitats. The resulting risk distribution map for snail habitats not only provides valuable insights but also serves as a guiding tool for targeted monitoring and control measures. The holds particular significance within the contest of the Yangtze River protection and restoration projects.

BackgroundFood-borne trematodiases (FBTs), mainly encompassing clonorchiasis, fascioliasis, fasciolopsiasis, opisthorchiasis, and paragonimiasis, is a neglected public health problem, particularly in the WHO South-East Asia and the Western Pacific regions. This study evaluates the global, regional, and national disease burden of FBTs from 1990 to 2021 and projects trends to 2030, underscore the need for targeted prevention and control.MethodsUsing the Global Burden of Disease 2021 database, the crude and the age-standardized prevalence rate (ASPR) and age-standardized prevalence disability-adjusted life years rate (ASDR) of FBTs at the global, regional and national level from 1990 to 2021 were described. The pivotal years of trend changes were identified using joinpoint regression analysis. The effects of age, period, cohort on FBTs prevalence and correlation with the sociodemographic index (SDI) was analyzed. Finally, the worldwide disability-adjusted life years (DALYs) for FBTs, projected up to 2030 using the Bayesian age-period-cohort model, were analyzed.ResultsIn 2021, 44,466,329 FBTs cases [95% uncertainty interval (UI): 40,017,217, 50,034,921], and 998,028 DALYs [95% UI: 569,766, 1,638,112] were estimated across 17 countries. The Western Pacific region exhibited the highest ASPR and ASDR, with the values of 1649.26 (95% UI: 1461.95, 1881.64) and 36.54 (95% UI: 19.77, 64.16), respectively. From 1990 to 2021, Lao PDR, Thailand, and the Philippines showed the most substantial declines in FBTs, while Kazakhstan had the largest average annual percentage change in DALYs (- 6.60, 95% UI: - 7.10, - 6.10). High-middle and middle SDI countries exhibited higher burden, with ASDR values of 28.03 (95% UI: 15.41, 48.73) and 16.63 (95% UI: 9.32, 27.68), respectively. The disease burden was greater among males, peaking in the 50-59 age group. The projected ASDR in 2030 is 13.10 for males and 8.40 for females.ConclusionsFBTs remain a public health threat, with the global ASDR projected to remain stable, showing only a slight decrease by 2030. Low-income countries face ambiguous mortality rates and underestimated disease burdens, highlighting the need for improved surveillance. To achieve the 2030 NTD goal, comprehensive surveillance and integrated strategies derived using a One Health approach should be prioritized to control FBTs effectively.

TRAF2 and NCK interacting kinase (TNIK), a critical interacting protein kinase, is currently receiving wide attention. TNIK is found in various human body organs and tissues and participates in cell motility, proliferation, and differentiation. On the one hand, its aberrant expression is related to the onset and progression of numerous malignant tumors. On the other hand, TNIK is important in neuronal growth, proliferation, differentiation, and synaptic formation. Thus, the novel therapeutic strategies for targeting TNIK offer a promising direction for cancer, neurological or psychotic disorders. Here, we briefly summarized the biological information of TNIK, reviewed the role and regulatory mechanism in cancer and neuropsychiatric diseases, and introduced the research progress of inhibitors targeting TNIK. Taken together, this review hopes to contribute to the in-depth understanding of the function and regulatory mechanism of TNIK, which is of great significance for revealing the role of TNIK in the occurrence and treatment of diseases.

Respiratory disease caused by coronavirus infection remains a global health crisis. Although several SARS-CoV-2-specific vaccines and direct-acting antivirals are available, their efficacy on emerging coronaviruses in the future, including SARS-CoV-2 variants, might be compromised. Host-targeting antivirals provide preventive and therapeutic strategies to overcome resistance and manage future outbreak of emerging coronaviruses. Cathepsin L (CTSL) and calpain-1 (CAPN1) are host cysteine proteases which play crucial roles in coronaviral entrance into cells and infection-related immune response. Here, two peptidomimetic α-ketoamide compounds, 14a and 14b, were identified as potent dual target inhibitors against CTSL and CAPN1. The X-ray crystal structures of human CTSL and CAPN1 in complex with 14a and 14b revealed the covalent binding of α-ketoamide groups of 14a and 14b to C25 of CTSL and C115 of CAPN1. Both showed potent and broad-spectrum anticoronaviral activities in vitro, and it is worth noting that they exhibited low nanomolar potency against SARS-CoV-2 and its variants of concern (VOCs) with EC50 values ranging from 0.80 to 161.7 nM in various cells. Preliminary mechanistic exploration indicated that they exhibited anticoronaviral activity through blocking viral entrance. Moreover, 14a and 14b exhibited good oral pharmacokinetic properties in mice, rats and dogs, and favorable safety in mice. In addition, both 14a and 14b treatments demonstrated potent antiviral potency against SARS-CoV-2 XBB 1.16 variant infection in a K18-hACE2 transgenic mouse model. And 14b also showed effective antiviral activity against HCoV-OC43 infection in a mouse model with a final survival rate of 60%. Further evaluation showed that 14a and 14b exhibited excellent anti-inflammatory effects in Raw 264.7 mouse macrophages and in mice with acute pneumonia. Taken together, these results suggested that 14a and 14b are promising drug candidates, providing novel insight into developing pan-coronavirus inhibitors with antiviral and anti-inflammatory properties.

The molecular representation model is a neural network that converts molecular representations (SMILES, Graph) into feature vectors, and is an essential module applied across a wide range of artificial intelligence-driven drug discovery scenarios. However, current molecular representation models rarely consider the three-dimensional conformational space of molecules, losing sight of the dynamic nature of small molecules as well as the essence of molecular conformational space that covers the heterogeneity of molecule properties, such as the multi-target mechanism of action, recognition of different biomolecules, dynamics in cytoplasm and membrane. In this study, a new model named GeminiMol is proposed to incorporate conformational space profiles into molecular representation learning, which extracts the feature of capturing the complicated interplay between the molecular structure and the conformational space. Although GeminiMol is pre-trained on a relatively small-scale molecular dataset (39290 molecules), it shows balanced and superior performance not only on 67 molecular properties predictions but also on 73 cellular activity predictions and 171 zero-shot tasks (including virtual screening and target identification). By capturing the molecular conformational space profile, the strategy paves the way for rapid exploration of chemical space and facilitates changing paradigms for drug design.

The main protease (Mpro) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) represents a promising target for antiviral drugs aimed at combating COVID-19. Consequently, the development of Mpro inhibitor is an ideal strategy for combating the virus. In this study, we identified twenty-two dithiocarbamates (1 a-h), dithiocarbamate-Cu(II) complexes (2 a-hCu) and disulfide derivatives (2 a-e, 2 i) as potent inhibitors of Mpro, with IC50 value range of 0.09-0.72, 0.9-24.7, and 15.1-111 μM, respectively, through FRET screening. The enzyme kinetics, inhibition mode, jump dilution, and DTT assay revealed that 1 g may be a partial reversible inhibitor, while 2 d and 2 f-Cu are the irreversible and dose- and time-dependent inhibitors, potentially covalently binding to the target. Binding of 2 d, 2 f-Cu, and 1 g to Mpro was found to decrease the stability of the protein. Additionally, DTT assays and thermal shift assays indicated that 2 f-Cu and 2 d are the nonspecific and promiscuous cysteine protease inhibitor. ICP-MS implied that the inhibitory activity of 2 f-Cu may stem from the uptake of Cu(II) by the enzyme. Cytotoxicity assays demonstrated that 2 d and 1 g exhibit low cytotoxicity, whereas 2 f-Cu show certain cytotoxicity in L929 cells. Overall, this work presents two promising scaffolds for the development of Mpro inhibitors to combat COVID-19.