Despite breakthroughs in immunotherapy for solid tumors, significant variations in treatment efficacy persist. Up to 80% of cancer patients suffer from malnutrition, which leads to: lymphoid atrophy and reduced T-cell reserves; deficiency of substrates required for T-cell activation and expansion; concurrent inflammation hindering T-cell infiltration into tumors; and cachexia accelerating PD-1 antibody clearance. Clinical studies confirm that severe malnutrition significantly impairs immune responses and increases the risk of treatment toxicity. Therefore, implementing standardized nutritional therapy is crucial for optimizing the reserve, activation, expansion, and infiltration capacity of immune cells, thereby providing a sound immune system foundation for immunotherapy. Immunonutrition therapy, by enhancing immunonutrients such as arginine, omega-3 polyunsaturated fatty acids, and nucleotides, reduces the secretion of pro-inflammatory mediators and promotes T-cell activation and proliferation. This enhances anti-tumor immune responses, prolongs survival, and advances cancer treatment towards multimodal combination and precision approaches.

Travelling wave structures for lossless ion manipulations(TW-SLIM)employ travelling wave electric fields to propel ions forward,enabling exceptionally long transmission paths and holding great potential for applications in material transportation and separation.In this study,different from previous studies focusing on the transport performance of macromolecules such as proteins in TW-SLIM,the transmission performance of small molecules(<200 amu)was investigated and analyzed in the turning TW-SLIM through the COMSOL simulation platform,to explore the influence of electrostatic field of protective electrode and radio frequency(RF)electric field on ion transport efficiency,and obtain the optimal value.Compared to macromolecules,small molecules required lower voltage amplitudes from guard electrodes but stricter requirements in terms of the peak-to-peak amplitude and frequency of RF voltage for lossless transmission.Using dimethyl methylphosphonate(DMMP)as a sample and testing it on the TW-SLIM experimental platform,when the protective voltage amplitude was 5 V and the peak-to-peak voltage of the radio-frequency electrode was 440 V at 1.5 MHz,the ion transmission efficiency reached 100%,achieving lossless transmission.The experimental results provided valuable references for application of TW-SLIM in separation and detection of small molecular substances,such as explosives and drugs.

Clustered regularly interspaced short palindromic repeats-associated proteins(CRISPR-Cas)system has emerged as a next-generation nucleic acid detection tool due to its precise gene editing capabilities and exhibits high specificity and significant potential for application in the diagnosis of pathogen.However,the inherent shortcomings of CRISPR-Cas,including insufficient sensitivity of the traditional CRISPR-Cas system,complex operation of the CRISPR-Cas system combined with amplification,and limited capability for multi-target detection,have significantly constrained its practical applications in clinical settings.With the advantages of miniaturization,integration and automation,microfluidics has emerged as a promising tool for advancing the development of point-of-care testing(POCT)platforms.The integration of microfluidic technology with CRISPR-Cas system not only enhances the detection throughput and efficiency significantly,but also drives innovation in the development of portable POCT devices.In this paper,a comprehensive review of the research advancements of CRISPR-Cas nucleic acid detection platform facilitated by microfluidic technology was presented,with a focus on their application in detection of pathogens associated with clinical disease.This study aimed to explore emerging molecular diagnostic methodologies and offered novel insights for future research in clinical pathogen detection.

ObjectiveTo observe the effect of Weichang'an prescription-containing serum on ferroptosis of human gastric cancer cells and explore the possible mechanism. MethodsSD rats were administrated with 18， 36， 72 g·kg^-1·d^-1 Weichang'an prescription by gavage for preparation of serum samples containing different doses of Weichang'an prescription， which were then used to treat MKN-45 cells. The cell proliferation was examined by the cell counting kit-8 （CCK-8）. In addition， inhibitors of apoptosis， necroptosis， and ferroptosis were added， and the survival of the cells treated with the serum samples was observed. The fluorescent probe dichlorodihydrofluorescein diacetate （DCF-DA） and the lipid peroxidation sensor C11-BODIPY were employed to detect the intracellular levels of reactive oxygen species （ROS） and lipid peroxidation， respectively. The levels of ferrous ion （Fe²⁺）， glutathione （GSH）， and malondialdehyde （MDA） were detected by enzyme-linked immunosorbent assay （ELISA）. Real-time PCR and Western blotting were employed to determine the expression of nuclear factor erythroid 2-related factor 2 （Nrf2）， aldo-keto reductase family 1 member B1 （AKR1B1）， glutathione peroxidase 4 （GPX4）， acyl-CoA synthetase long-chain family member 4 （ACSL4）， signal transducer and activator of transcription 3 （STAT3）， and mitogen-activated protein kinase （MAPK）. ResultsCompared with the blank group， Weichang'an prescription-containing serum decreased the viability of MKN-45 cells （P<0.05， P<0.01） in a time- and dose-dependent manner. Compared with the Weichang'an prescription group， the apoptosis inhibitor+Weichang'an prescription group and the ferroptosis inhibitor+Weichang'an prescription group showed increased cell viability （P<0.05， P<0.01）. Compared with the blank group， Weichang'an prescription elevated the levels of ROS， lipid peroxidation， and intracellular Fe²⁺ and MDA （P<0.05， P<0.01） and lowered the level of GSH （P<0.05， P<0.01） in a dose-dependent manner. Compared with the blank group， Weichang'an prescription down-regulated the mRNA and protein levels of Nrf2， AKR1B1， and GPX4 （P<0.05， P<0.01） and up-regulated the mRNA and protein levels of ACSL4 （P<0.05， P<0.01） in a dose-dependent manner. Compared with the blank group， Weichang'an prescription down-regulated the protein levels of p-STAT3 and p-ERK （P<0.05， P<0.01） in a dose-dependent manner. ConclusionThe Weichang'an prescription-containing serum can promote the ferroptosis and inhibit the proliferation of MKN-45 cells by regulating the STAT3 and MAPK pathways.

Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.

This study predicts the quality markers(Q-markers) for the cough-relieving and phlegm-expelling effects of Kening Granules based on pharmacodynamics, plasma drug chemistry, network pharmacology, and pharmacokinetics. Strong ammonia solution spray and phenol red secretion assays were employed to evaluate the cough-relieving and phlegm-expelling effects of Kening Granules. Twentysix absorbed prototype components of Kening Granules were identified by ultra high performance liquid chromatography coupled with QExactive Plus quadrupole/Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Plus Orbitrap HRMS). Through network pharmacology, 11 potential active components were screened out for the cough-relieving and phlegm-expelling effects of Kening Granules. The 11 components acted on 40 common targets such as IL6, TLR4, and STAT3, which mainly participated in PI3K/Akt, HIF-1, and EGFR signaling pathways. Pharmacokinetic quantitative analysis was performed for 7 prototype components. Three compounds including azelaic acid, caffeic acid, and vanillin were identified as Q-markers for the cough-relieving and phlegm-expelling effects of Kening Granules based on their effectiveness, transmissibility, and measurability. The results of this study are of great significance for clarifying the pharmacological substance basis, optimizing the quality standards, and promoting the clinical application of Kening Granules.
Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Cough/blood* ; Male ; Humans ; Animals ; Rats ; Rats, Sprague-Dawley ; Biomarkers/blood* ; Quality Control ; Chromatography, High Pressure Liquid ; Antitussive Agents/chemistry*

Nine novel compounds, comprising seven tetrahydroanthraquinones (auxarthrolones A-G, 1-7), a γ-butenolide glycoside (malfilamentoside E, 26), and a γ-butenolide (auxarthrolide A, 27), together with eighteen known compounds (8-25) were isolated from rice-based solid culture of Auxarthron umbrinum (A. umbrinum) DSM3193 using the one strain many compounds (OSMAC) approach. The structural elucidation of these compounds was accomplished through nuclear magnetic resonance (NMR), mass spectrometry (MS), and NMR calculation combined with DP4+ analysis or MAEΔΔδ parameter, while the absolute configurations of new compounds were established through single-crystal X-ray diffraction, electronic circular dichroism (ECD) spectroscopic data analysis and/or chemical derivatization. Austrocortilutein (10) and auxarthrol H (14) demonstrated moderate cytotoxicity against U87 and U251 [half maximal inhibitory concentration (IC₅₀) 3.5-12.1 μmol·L^-1]. Additionally, auxarthrolone A (1), auxarthrol H (14), eupolyphagin B (15), and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (17) exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid, thus demonstrating fibroblast proliferation-promoting activity.
4-Butyrolactone/pharmacology* ; Molecular Structure ; Anthraquinones/pharmacology* ; Humans ; Animals ; Mice ; Cell Line, Tumor ; Magnetic Resonance Spectroscopy

OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

OBJECTIVE: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351). METHODS: K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot. RESULTS: Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks. CONCLUSION These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals ; COVID-19/genetics* ; Mice ; Brain/metabolism* ; Apoptosis ; Mice, Inbred C57BL ; SARS-CoV-2/physiology* ; Pyroptosis ; Gene Expression Profiling ; Transcriptome ; Male ; Female