Topical delivery of a human single-domain antibody targeting IL-33 to inhibit mucosal inflammation.

Addressing mucosal inflammatory disorders in the ocular surface or respiratory system remains a formidable challenge owing to the limited penetration of biological therapeutics across epithelial barriers. In this study, we explored the potential of human single-domain antibodies (UdAbs) as topical therapeutics for the targeted modulation of interleukin-33 (IL-33) in two mucosal-associated inflammatory disorders. The anti-IL-33 UdAb A12 demonstrated potent inhibition of the IL-33-mediated signaling pathway, despite not potently blocking the IL-33 receptor interaction.

Enhancing vaccine half-life as a novel strategy for improving immune response durability of subunit vaccines.

Vaccines are widely regarded as one of the most effective strategies for combating infectious diseases. However, significant challenges remain, such as insufficient antibody levels, limited protection against rapidly evolving variants, and poor immune durability, particularly in subunit vaccines, likely due to their short in vivo exposure. Recent advances in extending the half-life of protein therapeutics have shown promise in improving drug efficacy, yet whether increasing in vivo persistence can enhance the efficacy of subunit vaccines remains underexplored.

Breviane Spiroditerpenoids with Anti-inflammatory and Antiviral Activities from Deep-Sea-Derived Fungus sp. F59.

Twelve new breviane spiroditerpenoids, namely, chrysobreviones A-L (-), together with seven structurally related analogues (-) were isolated from the EtOAc extract of the fermented cultures of deep-sea-derived fungus sp. F59. These structures including absolute configurations were resolved on the basis of extensive analysis of NMR spectroscopic data and HRESIMS, in association with experimental and calculated ECD data as well as the modified Mosher's method.

Fully human single-domain antibody targeting a highly conserved cryptic epitope on the Nipah virus G protein.

Nipah virus infection, one of the top priority diseases recognized by the World Health Organization, underscores the urgent need to develop effective countermeasures against potential epidemics and pandemics. Here, we identify a fully human single-domain antibody that targets a highly conserved cryptic epitope situated at the dimeric interface of the Nipah virus G protein (receptor binding protein, RBP), as elucidated through structures by high-resolution cryo-electron microscopy (cryo-EM). This unique binding mode disrupts the tetramerization of the G protein, consequently obstructing the activation of the F protein and inhibiting viral membrane fusion.

Infection associated with CDK4/6 inhibitors: a pharmacovigilance analysis of the FDA adverse event reporting system database.

Introduction: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are first-line treatments for hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer. With their increasing clinical use, infection-related adverse events (AEs) associated with CDK4/6 inhibitors have been widely reported in recent years. This study aimed to analyze the occurrence of infections associated with the CDK4/6 inhibitors (palbociclib, ribociclib and abemaciclib) based on the real-world data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Hydrogel microrobots for biomedical applications.

Recent years have witnessed a surge in the application of microrobots within the medical sector, with hydrogel microrobots standing out due to their distinctive advantages. These microrobots, characterized by their exceptional biocompatibility, adjustable physico-mechanical attributes, and acute sensitivity to biological environments, have emerged as pivotal tools in advancing medical applications such as targeted drug delivery, wound healing enhancement, bio-imaging, and precise surgical interventions. The capability of hydrogel microrobots to navigate and perform tasks within complex biological systems significantly enhances the precision, efficiency, and safety of therapeutic procedures.

Semisynthesis of homogeneous spike RBD glycoforms from SARS-CoV-2 for profiling the correlations between glycan composition and function.

Vaccines have been the primary remedy in the global fight against coronavirus disease 2019 (COVID-19). The receptor-binding domain (RBD) of the spike protein, a critical viral immunogen, is affected by the heterogeneity of its glycan structures and relatively low immunogenicity. Here, we describe a scalable synthetic platform that enables the precise synthesis of homogeneously glycosylated RBD, facilitating the elucidation of carbohydrate structure-function relationships.

Prognostic value and immune regulatory role of dynamin 1-like in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is the most common histological subtype of non-small cell lung cancer (NSCLC), with poor treatment outcomes worldwide. Dynamin-related protein 1 (DRP1), which is encoded by the dynamin 1-like () gene, acts as a regulator of mitochondrial fission and plays crucial roles in tumor initiation and progression. However, the clinical value and immune regulation of in LUAD have not been explored.

Multimode microdimer robot for crossing tissue morphological barrier.

Swimming microrobot energized by magnetic fields exhibits remotely propulsion and modulation in complex biological experiment with high precision. However, achieving high environment adaptability and multiple tasking capability in one configuration is still challenging. Here, we present a strategy that use oriented magnetized Janus spheres to assemble the microdimer robots with two magnetic distribution configurations of head-to-side configuration (HTS-config) and head-to-head configuration (HTH-config), achieving performance of multiple tasks through multimode transformation and locomotion.

A novel prognostic classification integrating lipid metabolism and immune co-related genes in acute myeloid leukemia.

Background: As a severe hematological malignancy in adults, acute myeloid leukemia (AML) is characterized by high heterogeneity and complexity. Emerging evidence highlights the importance of the tumor immune microenvironment and lipid metabolism in cancer progression. In this study, we comprehensively evaluated the expression profiles of genes related to lipid metabolism and immune modifications to develop a prognostic risk signature for AML.

Small molecular inhibitors for KRAS-mutant cancers.

Three rat sarcoma (RAS) gene isoforms, KRAS, NRAS, and HRAS, constitute the most mutated family of small GTPases in cancer. While the development of targeted immunotherapies has led to a substantial improvement in the overall survival of patients with non-KRAS-mutant cancer, patients with RAS-mutant cancers have an overall poorer prognosis owing to the high aggressiveness of RAS-mutant tumors. KRAS mutations are strongly implicated in lung, pancreatic, and colorectal cancers.

The emerging role of copper in depression.

Copper (Cu) is an essential trace element in the brain and serves as an important cofactor for numerous enzymes involved in a wide range of biochemical processes including neurobehavioral, mitochondrial respiration, and antioxidant effects. Recent studies have demonstrated that copper dyshomeostasis is tightly associated with the development of depression by inducing oxidative stress and inflammatory responses. However, these findings have remained controversial so far.

ARHGAP9 knockdown promotes lung adenocarcinoma metastasis by activating Wnt/β-catenin signaling pathway via suppressing DKK2.

This study aims to elucidate the effect of ARHGAP9 on lung adenocarcinoma (LUAD) metastasis, and preliminarily explore its molecular mechanism. As a result, we found that ARHGAP9 was downregulated and correlated with poor prognosis of LUAD. ARHGAP9 knockdown promoted LUAD cell proliferation, migration and invasion, inhibited cell apoptosis and reduced G0G1 cell cycle arrest, in contrast to the results of ARHGAP9 overexpression.

Tumor necrosis factor-related lncRNAs predict prognosis and immunotherapy response for patients with lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) has become one of the most lethal cancers, for which the recurrence and survival rates remain unfavorable. The tumor necrosis factor (TNF) family is involved in tumorigenesis and tumor progression. Various long non-coding RNAs (lncRNAs) play important roles by mediating the TNF family in cancer.

Metabolomics Identifies a Panel of Diagnostic Biomarkers for Early Human Embryonic Development Arrest.

Early embryonic development arrest (EEDA) is a unique form of early spontaneous abortion in pregnant women, which is previously suggested to be associated with metabolic abnormalities. Noninvasive biomarkers would significantly improve its diagnosis and clinical outcome. Here, we performed a targeted metabolomics study in plasma from EEDA patients ( = 27) and normal pregnant women (NPW, = 27) using liquid chromatography coupled with mass spectrometry (LC-MS) to identify potential diagnostic marker metabolites.

Amoeba-Inspired Magnetic Venom Microrobots.

Nature provides a successful evolutionary direction for single-celled organisms to solve complex problems and complete survival tasks - pseudopodium. Amoeba, a unicellular protozoan, can produce temporary pseudopods in any direction by controlling the directional flow of protoplasm to perform important life activities such as environmental sensing, motility, predation, and excretion. However, creating robotic systems with pseudopodia to emulate environmental adaptability and tasking capabilities of natural amoeba or amoeboid cells remains challenging.

Breaking through Barriers: Ultrafast Microbullet Based on Cavitation Bubble.

Micromotors hold great promise for extensive practical applications such as those in biomedical domains and reservoir exploration. However, insufficient propulsion of the micromotor limits its application in crossing biological barriers and breaking reservoir boundaries. In this study, an ultrafast microbullet based on laser cavitation that can utilize the energy of a cavitation bubble and realize its own hurtling motion is reported.

Clinical significance and immune landscape of cuproptosis-related lncRNAs in kidney renal clear cell carcinoma: a bioinformatical analysis.

Background: Kidney renal clear cell carcinoma (KIRC) is considered an immunogenic tumor. Cuproptosis is a newly identified copper-induced regulated cell death that relies on mitochondria respiration. Long noncoding RNAs (lncRNAs) have emerged as significant players in tumorigenesis and metastasis.

Chaetoglobosin E inhibits tumor growth and promotes the anti-tumor efficacy of cytotoxic drugs in esophageal squamous cell carcinoma by targeting PLK1.

Background: Currently, there is no satisfactory treatment available for esophageal squamous cell carcinoma (ESCC), and thus, there is a pressing need to develop effective drugs. Chaetoglobosin E, a cytochalasan alkaloid derived from metabolites of 375, is a chaetoglobosin with intense anti-tumor activity. Therefore, revealing its anti-tumor mechanism for the application of cytochalasans is crucial.

A reporting quality evaluation of the clinical practice guidelines for bladder cancer based on the RIGHT checklist.

Background: The Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist was developed to improve the reporting quality in clinical practice guidelines (CPGs). CPGs could provide the recommendations for key clinical issues with alternative care options and adherence to them could improve the outcomes. And, high reporting quality CPGs can assist health workers to incorporate the best evidence into the individual practice.

An EGFR/HER2-targeted conjugate sensitizes gemcitabine-sensitive and resistant pancreatic cancer through different SMAD4-mediated mechanisms.

Chemoresistance limits its clinical implementation for pancreatic ductal adenocarcinoma (PDAC). We previously generated an EGFR/HER2 targeted conjugate, dual-targeting ligand-based lidamycin (DTLL), which shows a highly potent antitumor effect. To overcome chemoresistance in PDAC, we aim to study DTLL efficacy when combined with gemcitabine and explore its mechanisms of action.

First Nerve-Related Immunoprobe for Guidance of Renal Denervation through Colocalization of NIR-II and Photoacoustic Bioimaging.

Nerve-related fluorophores generally locate in the visible or near-infrared region with shallow penetration depth and easy uptake by surrounding tissues. Prolonging the optical window promotes resolution by minimizing photoscattering and eliminating autofluorescence for NIR-II (second near infrared; 1000-1700 nm) and photoacoustic bioimaging. In addition, combination of the two could help in colocalization of targets at the 3D level.

A distinct lipid metabolism signature of acute myeloid leukemia with prognostic value.

Background: Acute myeloid leukemia (AML) is a highly aggressive hematological malignancy characterized by extensive genetic abnormalities that might affect the prognosis and provide potential drug targets for treatment. Reprogramming of lipid metabolism plays important roles in tumorigenesis and progression and has been newly recognized a new hallmark of malignancy, and some related molecules in the signal pathways could be prognostic biomarkers and potential therapeutic targets for cancer treatment. However, the clinical value of lipid metabolism reprogramming in AML has not been systematically explored.