Proteolysis-targeting chimera-doxorubicin conjugate nanoassemblies for dual treatment of EGFR-TKI sensitive and resistant non-small cell lung cancer.

Proteolysis-targeting chimeras (PROTACs) have emerged as a promising strategy for targeted protein degradation and drug discovery. However, traditional PROTACs face inherent limitations and may also contribute to induce drug resistance. These challenges have driven the development of innovative strategies to overcome these obstacles.

Associations between surrogate insulin resistance indexes and osteoarthritis: NHANES 2003-2016.

Insulin resistance (IR) and abdominal obesity are key in osteoarthritis (OA) development. The triglyceride glucose (TyG) index, along with indicators such as the visceral adiposity index (VAI), and lipid accumulation product (LAP), are increasingly used to measure IR. This study aims to explore the associations between surrogate IR indexes and OA, assessing their diagnostic efficacy within American populations.

Development and validation of a new nomogram for self-reported OA based on machine learning: a cross-sectional study.

Developing a new diagnostic prediction model for osteoarthritis (OA) to assess the likelihood of individuals developing OA is crucial for the timely identification of potential populations of OA. This allows for further diagnosis and intervention, which is significant for improving patient prognosis. Based on the NHANES for the periods of 2011-2012, 2013-2014, and 2015-2016, the study involved 11,366 participants, of whom 1,434 reported a diagnosis of OA.

[Construction of regional ecological security pattern based on the "sensitivity-importance-connectivity" framework: A case study of Guizhou Province].

The construction of an ecological security pattern is crucial to maintain ecosystem health and stability, with great significance for regional sustainable development. Following the research paradigm of "ecological source areas-ecological resistance surfaces-ecological corridors", based on the index framework of "sensitivity-importance-connectivity", we identified the ecological source areas, generated the ecological resistance surface through graded weighting of underlying surface factors and point of interest (POI) method, determined the ecological corridor, pinch point, and obstacle area using circuit theory, and constructed the ecological security pattern of Guizhou Pro-vince. Results showed that the areas of extremely sensitive of rocky desertification and soil erosion and the areas of extremely important areas of water resources forming, soil and water conservation and biodiversity in Guizhou Pro-vince were generally small and distributed differently, accounting for 1.

[Differences in components and anti-inflammatory and analgesic activities of two phase states of Wuzhuyu Decoction].

This study rapidly identified and quantified the chemical components of the Wuzhuyu Decoction nanophase(WZYD-N) and suspension phase(WZYD-S) using ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry(UPLC-QQQ-MS/MS). Based on preliminary pharmacodynamic experiments and network pharmacology analysis, the differential anti-inflammatory and analgesic activities of WZYD-N and WZYD-S were explored to understand their pharmacodynamic basis. WZYD-N and WZYD-S were separated by differential centrifugation-dialysis, and their particle size, Zeta potential, PDI, and morphology were characterized by dynamic light scattering and transmission electron microscopy.

NIR-II AIE Liposomes for Boosting Type-I Photodynamic and Mild-Temperature Photothermal Therapy in Breast Cancer Treatment.

Phototheranositcs has recently aroused extreme attention due to its exceptional advantages. However, the poor photothernostic efficiency, limited penetration depth, strong oxygen-dependence, and inevitable damage to normal tissue of conventional photothernostic materials severely hindered their total theranostic efficacy. Herein, a series of near-infrared second (NIR-II) photosensitizers (PSs) featuring aggregation-induced emission (AIE), NIR-II fluorescence imaging (FLI), type I photodynamic therapy (PDT) and mild-temperature photothermal therapy (PTT) are constructed through dual-strategy methods combining donor group engineering and fluorination engineering.

Donor-acceptor-donor type AIEgens based on thieno[3.4-c]pyrrole-4,6-dione: Synthesis, electropolymerization, and electrochromism.

Photoelectric functional materials with electrochemical reversible activity and fluorescence intensities have attracted significant interest due to their wide range of applications in optoelectronic devices. In this work, a series of photoresponsive and electroactive monomers based on thieno[3.4-c]pyrrole-4,6-dione (TPD) are synthesized and characterized.

Cryo-electron tomography elucidates annular intraluminal configurations in Caenorhabditis elegans microtubules.

Background Information: Microtubules serve as integral components in cellular operations such as cell division, intracellular trafficking, and cellular architecture. Composed of tubulin protein subunits, these hollow tubular structures have been increasingly elucidated through advanced cryo-electron microscopy (Cryo-EM), which has unveiled the presence of microtubule inner proteins (MIPs) within the microtubular lumen.

Results: In the present investigation, we employ a synergistic approach incorporating high-pressure freezing, cryo-focused ion beam milling, and Cryo-electron tomography (Cryo-ET) to interrogate the in situ architecture of microtubules in Caenorhabditis elegans larvae.

Overview of Panax ginseng and its active ingredients protective mechanism on cardiovascular diseases.

Ethnic Pharmacological Relevance: Panax ginseng is a traditional Chinese herbal medicine used to treat cardiovascular diseases (CVDs), and it is still widely used to improve the clinical symptoms of various CVDs. However, there is currently a lack of summary and analysis on the mechanism of Panax ginseng exerts its cardiovascular protective effects. This article provides a review of in vivo and in vitro pharmacological studies on Panax ginseng and its active ingredients in reducing CVDs damage.

Folate-PEG-PROTAC Micelles for Enhancing Tumor-Specific Targeting Proteolysis In Vivo.

Proteolysis targeting chimeras (PROTACs) technology is rapidly developed as a novel and selective medicinal strategy for the degradation of cellular proteins in cancer therapy. However, the applications of PROTACs as heterobifunctional molecules are largely limited by high molecular weight, low bioavailability, poor permeability, insufficient targeting, and low efficacy in vivo. Herein, self-assembling micelles of FA-PEG-PROTAC are designed for cancer cell selective targeting and reductive-response proteolysis in tumor-bearing mice.

Recent Advances in Understanding the Regulatory Mechanism of Plasma Membrane H+-ATPase through the Brassinosteroid Signaling Pathway.

The polyhydroxylated steroid phytohormone brassinosteroid (BR) controls many aspects of plant growth, development and responses to environmental changes. Plasma membrane (PM) H+-ATPase, the well-known PM proton pump, is a central regulator in plant physiology, which mediates not only plant growth and development, but also adaptation to stresses. Recent studies highlight that PM H+-ATPase is at least partly regulated via the BR signaling.

The combined application of ear acupuncture in the treatment of allergic rhinitis: A meta-analysis.

Objective: Meta-analysis was used to evaluate the clinical efficacy of auricular acupressure in the treatment of allergic rhinitis.

Methods: Randomised controlled trials (RCTS) on the treatment of allergic rhinitis with ear acupuncture were searched by computer in PubMed, Cochrane Library, Embase、Web of Science、China National Knowledge Infrastructure (CNKI), Wanfang Database (Wanfang), VIP database, and China Biomedical Literature Service System (CBM). The search time was from the establishment of the database to September 18, 2022.

Vimentin regulates nuclear segmentation in neutrophils.

Granulocytes are indispensable for various immune responses. Unlike other cell types in the body, the nuclei of granulocytes, particularly neutrophils, are heavily segmented into multiple lobes. Although this distinct morphological feature has long been observed, the underlying mechanism remains incompletely characterized.

HIF-1α regulates the cell viability in radioiodine-resistant papillary thyroid carcinoma cells induced by hypoxia through PKM2/NF-κB signaling pathway.

The curative treatment options for papillary thyroid cancer (PTC) encompass surgical intervention, radioactive iodine administration, and chemotherapy. However, the challenges of radioiodine (RAI) resistance, metastasis, and chemotherapy resistance remain inadequately addressed. The objective of this study was to investigate the protective role of hypoxia-inducible factor-1α (HIF-1α) in I-resistant cells and a xenograft model under hypoxic conditions, as well as to explore potential mechanisms.

Heterologous expression of a deacetylase and its application in L-glufosinate preparation.

With potent herbicidal activity, biocatalysis synthesis of L-glufosinate has drawn attention. In present research, NAP-Das2.3, a deacetylase capable of stereoselectively resolving N-acetyl-L-glufosinate to L-glufosinate mined from Arenimonas malthae, was heterologously expressed and characterized.

[Microbial production of S-adenosyl-l-methionine: a review].

S-adenosyl-l-methionine (SAM) is ubiquitous in living organisms and plays important roles in transmethylation, transsulfuration and transamination in organisms. Due to its important physiological functions, production of SAM has attracted increasing attentions. Currently, researches on SAM production mainly focus on microbial fermentation, which is more cost-effective than that of the chemical synthesis and the enzyme catalysis, thus easier to achieve commercial production.

PHLDA1 is a P53 target gene involved in P53-mediated cell apoptosis.

Pleckstrin homeolike domain, family A, member 1 (PHLDA1) is a multifunctional protein that plays diverse roles in A variety of biological processes, including cell death, and hence its altered expression has been found in different types of cancer. Although studies have shown a regulatory relationship between p53 and PHLDA1, the molecular mechanism is still unclear. Especially, the role of PHLDA1 in the process of apoptosis is still controversial.

Biomedical named entity recognition based on fusion multi-features embedding.

Background: With the exponential increase in the volume of biomedical literature, text mining tasks are becoming increasingly important in the medical domain. Named entities are the primary identification tasks in text mining, prerequisites and critical parts for building medical domain knowledge graphs, medical question and answer systems, medical text classification.

Objective: The study goal is to recognize biomedical entities effectively by fusing multi-feature embedding.

In situ snapshots along a mammalian selective autophagy pathway.

Selective macroautophagy (hereafter referred to as autophagy) describes a process in which cytosolic material is engulfed in a double membrane organelle called an autophagosome. Autophagosomes are carriers responsible for delivering their content to a lytic compartment for destruction. The cargo can be of diverse origin, ranging from macromolecular complexes to protein aggregates, organelles, and even invading pathogens.

The Microbiota-Dependent Treatment of Wuzhuyu Decoction for Chronic Migraine Model Rat Associated with Anxiety-Depression Like Behavior.

We previously found that Wuzhuyu Decoction (WZYD) could affect central and peripheral 5-HT to relieve hyperalgesia in chronic migraine (CM) model rats, possibly related to gut microbiota. However, the exact role of gut microbiota has not been elucidated. Accumulating evidence points to the possibility of treating central nervous system disease via the gut-brain axis.

Effects of chronic heat stress on the immunophenotyping of lymphocytes in immune organs of growing pigs.

This study aimed to investigate the effects of chronic heat stress on the immunophenotyping of lymphocytes in immune organs of growing pigs. A single-factor randomized block design was used, and 15 healthy growing large white barrows (5 litters, 3 pigs/litter) with similar body weight (40.8 kg) were assigned into 3 groups (5 pigs in each group).

An Ensemble Semantic Textual Similarity Measure Based on Multiple Evidences for Biomedical Documents.

With the increasing volume of the published biomedical literature, the fast and effective retrieval of the literature on the sequence, structure, and function of biological entities is an essential task for the rapid development of biology and medicine. To capture the semantic information in biomedical literature more effectively when biomedical documents are clustered, we propose a new multi-evidence-based semantic text similarity calculation method. Two semantic similarities and one content similarity are used, in which two semantic similarities include MeSH-based semantic similarity and word embedding-based semantic similarity.

Improvement of S-adenosyl-L-methionine production in S by atmospheric and room temperature plasma-ultraviolet compound mutagenesis and droplet microfluidic adaptive evolution.

To improve S-Adenosyl-L-methionine (a compound with important physiological functions, SAM) production, atmospheric and room temperature plasma and ultraviolet-LiCl mutagenesis were carried out with strain ZY 1-5. The mutants were screened with ethionine, L-methionine, nystatin and cordycepin as screening agents. Adaptive evolution of a positive mutant UV6-69 was further performed by droplet microfluidics cultivation with ethionine as screening pressure.