Hypoxia Reversion and STING Pathway Activation through Large Mesoporous Nanozyme for Near-Infrared-II Light Amplified Tumor Polymetallic-Immunotherapy.

cGAS/STING pathway, which is highly related to tumor hypoxia, is considered as a potential target for remodeling the immunosuppressive microenvironment of solid tumors. Metal ions, such as Mn, activate the cGAS/STING pathway, but their efficacy in cancer therapy is limited by insufficient effect on immunogenic tumor cell death of a single ion. Here, we evaluate the association between tumor hypoxia and cGAS/STING inhibition and report a polymetallic-immunotherapy strategy based on large mesoporous trimetal-based nanozyme (AuPdRh) coordinated with Mn (Mn@AuPdRh) to activate cGAS/STING signaling for robust adaptive antitumor immunity.

Photothermal-Based Multiplex Nested Digital PCR System for Rapid Detection of Foodborne Pathogens.

The rapid and sensitive detection of foodborne pathogens is crucial for ensuring food safety. Among virus testing methods, polymerase chain reaction (PCR) has served as the gold-standard technique in most food safety regulation organizations. However, to enhance the speed and efficiency of PCR, novel approaches are continually being explored.

CXCL5 activates CXCR2 in nociceptive sensory neurons to drive joint pain and inflammation in experimental gouty arthritis.

Gouty arthritis evokes joint pain and inflammation. Mechanisms driving gout pain and inflammation remain incompletely understood. Here we show that CXCL5 activates CXCR2 expressed on nociceptive sensory neurons to drive gout pain and inflammation.

Liensinine, a Novel and Food-Derived Compound, Exerts Potent Antihepatoma Efficacy via Inhibiting the Kv10.1 Channel.

Plant metabolites from natural product extracts offer unique advantages against carcinogenesis in the development of drugs. The target-based virtual screening from food-derived compounds represents a promising approach for tumor therapy. In this study, we performed virtual screening to target the presumed inhibitor-binding pocket and identified a highly potent Kv10.

Corydaline binds to a druggable pocket of hEAG1 channel and inhibits hepatic carcinoma cell viability.

Ether-à-go-go (EAG) potassium channels play a crucial role in the regulation of neuronal excitability and cancer progression, rendering them potential drug targets for cancer therapy. However, the scarcity of information regarding the selection sites on hEAG1 has posed a challenge in the discovery of new hEAG1 inhibitors. In this study, we introduced a novel natural product, corydaline, which selectively inhibits the hEAG1 channel without sensitivity to other KCNH channels.

Inhibitory effect of daidzein on the calcium-activated chloride channel TMEM16A and its anti-lung adenocarcinoma activity.

TMEM16A is highly expressed in a variety of tumor cells and is involved in the growth and metastasis of malignancies. It has been established that down-regulation of TMEM16A expression or functional activity can inhibit tumor cells growth. However, there is a lack of targeted inhibitors with high efficiency and low toxicity.

Liposome-Templated Green Synthesis of Mesoporous Metal Nanostructures with Universal Composition for Biomedical Application.

Porous noble metal nanoparticles have received particular attention recently for their unique optical, thermal, and catalytic functions in biomedicine. However, limited progress has been made to synthesize such porous metallic nanostructures with large mesopores (≥25 nm). Here, a green yet facile synthesis strategy using biocompatible liposomes as templates to mediate the formation of mesoporous metallic nanostructures in a controllable fashion is reported.

Self-Association of ACE-2 with Different RBD Amounts: A Dynamic Simulation Perspective on SARS-CoV-2 Infection.

Transmissibility of SARS-CoV-2 initially relies on its trimeric Spike-RBDs to tether the ACE-2 on host cells, and enhanced self-association of ACE-2 engaged with Spike facilitates the viral infection. Two primary packing modes of Spike-ACE2 heteroproteins exist potentially due to discrepant amounts of RBDs loading on ACE-2, but the resultant self-association difference is inherently unclear. We used extensive coarse-grained dynamic simulations to characterize the self-association efficiency, the conformation relevance, and the molecular mechanism of ACE-2 with different RBD amounts.

Correction: Delivery mechanism of doxorubicin by PEG-DPPE micelles on membrane invasion by dynamic simulations.

Correction for 'Delivery mechanism of doxorubicin by PEG-DPPE micelles on membrane invasion by dynamic simulations' by Lina Zhao , , 2023, , 16114-16125, https://doi.org/10.1039/D2CP05946K.

Delivery mechanism of doxorubicin by PEG-DPPE micelles on membrane invasion by dynamic simulations.

Exploiting micelles of polyethylene glycol-dipalmitoylglycerophosphoethanolamine (PEG-DPPE) as a drug delivery approach is of great promise for improving therapeutic targeting and the half-lives of drugs. To optimize the micelle carriers, pending issues concerning the kinetics underlying the carrier-membrane interplay and the specific contributions of the micelle hydrophobic/hydrophilic components remain to be addressed. Relying on MARTINI coarse-grain (CG) molecular dynamics simulations, we explored the carrier-membrane fusion dynamics of PEG-DPPE micelles with different PEG repetitions in delivering doxorubicin (DOX).

Molecular basis of PIP2-dependent conformational switching of phosphorylated CD44 in binding FERM.

Association of the cellular adhesive protein CD44 and the N-terminal (FERM) domain of cytoskeleton adaptors is critical for cell proliferation, migration, and signaling. Phosphorylation of the cytoplasmic domain (CTD) of CD44 acts as an important regulator of the protein association, but the structural transformation and dynamics mechanism remain enigmatic. In this study, extensive coarse-grained simulations were employed to explore the molecular details in the formation of CD44-FERM complex under S291 and S325 phosphorylation, a modification path known to exert reciprocal effects on the protein association.

Identification of a druggable pocket of the calcium-activated chloride channel TMEM16A in its open state.

The calcium-activated chloride channel TMEM16A is a potential drug target to treat hypertension, secretory diarrhea, and several cancers. However, all reported TMEM16A structures are either closed or desensitized, and direct inhibition of the open state by drug molecules lacks a reliable structural basis. Therefore, revealing the druggable pocket of TMEM16A exposed in the open state is important for understanding protein-ligand interactions and facilitating rational drug design.

Computational and experimental studies of salvianolic acid A targets 3C protease to inhibit enterovirus 71 infection.

Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease caused by enterovirus (EV) infection. EV71 is one of the major pathogens causing hand, foot, and mouth disease and is more likely to cause exacerbation and death than other enteroviruses. Although a monovalent vaccine for EV71 has been developed, there are no clinically available anti-EV71 specific drugs.

Drug repurposing and molecular mechanisms of the antihypertensive drug candesartan as a TMEM16A channel inhibitor.

TMEM16A, a Ca-activated chloride channel (CaCC), and its pharmacological inhibitors can inhibit the growth of lung adenocarcinoma cells. However,the poor efficacy, safety, and stability of TMEM16A inhibitors limit the development of these agents. Therefore, finding new therapeutic directions from already marketed drugs is a feasible strategy to obtain safe and effective therapeutic drugs.

Synergistic effect of Ag and Cu on improvingbiological properties of KTiOnanowires for potential biomedical applications.

The development of novel antibacterial nano-materials with synergistic biological effects has attracted extensive interest of the researchers. In the study, 0.5 mol% Ag and 0.

Molecular mechanism of ion channel protein TMEM16A regulated by natural product of narirutin for lung cancer adjuvant treatment.

Cancer chemotherapy drugs are widely criticized for their serious side effects and low cure rate. Therefore, adjuvant therapy as a combination with chemotherapy administration is being accepted by many patients. However, unclear drug targets and mechanisms limit the application of adjuvant treatment.

General mechanism of spider toxin family I acting on sodium channel Nav1.7.

Various peptide toxins in animal venom inhibit voltage-gated sodium ion channel Nav1.7, including Nav-targeting spider toxin (NaSpTx) Family I. Toxins in NaSpTx Family I share a similar structure, i.

Multi-target tracheloside and doxorubicin combined treatment of lung adenocarcinoma.

Chemotherapy is one of the main methods for malignant lung cancer treatment. However, the side effects of chemotherapy drugs are serious and it is prone to drug resistance. Therefore, multi-drug combination chemotherapy is popular in lung cancer treatment.

Near-Infrared Light-Responsive Nanoinhibitors for Tumor Suppression through Targeting and Regulating Anion Channels.

The gated state of anion channels is involved in the regulation of proliferation and migration of tumors. Specific regulators are urgently needed for efficacious cancer ablation. For this purpose, it is essential to understand the molecular mechanisms of interaction between the regulators and anion channels and apply this knowledge to regulate anion channels.

Carrier-free nanoprodrug for p53-mutated tumor therapy via concurrent delivery of zinc-manganese dual ions and ROS.

Human cancers typically express a high level of tumor-promoting mutant p53 protein (Mutp53) with a minimal level of tumor-suppressing wild-type p53 protein (WTp53). In this regard, inducing Mutp53 degradation while activating WTp53 is a viable strategy for precise anti-tumor therapy. Herein, a new carrier-free nanoprodrug (.

Caffeic Acid, an Active Ingredient in Coffee, Combines with DOX for Multitarget Combination Therapy of Lung Cancer.

Adjuvant diet therapy is an important means of comprehensive treatment of cancer. It is recognized by patients for its high safety, painlessness, and ease to operate. However, the development of adjuvant dietary therapy is limited by unclear targets and unclear anticancer mechanisms.

Molecular mechanism of CD44 homodimerization modulated by palmitoylation and membrane environments.

The homodimerization of CD44 plays a key role in an intercellular-to-extracellular signal transduction and tumor progression. Acylated modification and specific membrane environments have been reported to mediate translocation and oligomerization of CD44; however, the underlying molecular mechanism remains elusive. In this study, extensive molecular dynamics simulations are performed to characterize the dimerization of palmitoylated CD44 variants in different bilayer environments.

Polyisocyanide hydrogels with tunable nonlinear elasticity mediate liver carcinoma cell functional response.

Hepatocellular carcinoma development is closely related to the changes in tissue mechanics induced by excess collagen deposition and crosslinking, which leads to liver fibrosis and malignant progression. The role of matrix stiffness has been widely assessed using various linearly elastic materials. However, the liver, like many soft tissues, also exhibits nonlinear elasticity by strain-stiffening, allowing cells to mechanically interact with their micromilieus which has attracted much attention in cellular processes recently.

A Review on the Role of TRP Channels and Their Potential as Drug Targets_An Insight Into the TRP Channel Drug Discovery Methodologies.

Transient receptor potential (TRP) proteins are a large group of ion channels that control many physiological functions in our body. These channels are considered potential therapeutic drug targets for various diseases such as neurological disorders, cancers, cardiovascular disease, and many more. The Nobel Prize in Physiology/Medicine in the year 2021 was awarded to two scientists for the discovery of TRP and PIEZO ion channels.

Anoctamin 1 controls bone resorption by coupling Cl channel activation with RANKL-RANK signaling transduction.

Osteoclast over-activation leads to bone loss and chloride homeostasis is fundamental importance for osteoclast function. The calcium-activated chloride channel Anoctamin 1 (also known as TMEM16A) is an important chloride channel involved in many physiological processes. However, its role in osteoclast remains unresolved.