Lung cancer is the most common malignant tumor worldwide, ranking first in both incidence and mortality rates. According to the latest statistics from the International Agency for Research on Cancer (IARC), approximately 2.5 million new cases and around 1.8 million deaths from lung cancer occurred in 2022, placing a tremendous burden on global healthcare systems. The high mortality rate of lung cancer is closely linked to its subtle early symptoms, which often lead to diagnosis at advanced stages. This not only complicates treatment but also results in substantial economic losses. Current treatment options for lung cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy, and immunotherapy. Among these, immunotherapy has emerged as the most groundbreaking advancement in recent years, owing to its unique antitumor mechanisms and impressive clinical benefits. Unlike traditional therapies such as radiotherapy and chemotherapy, immunotherapy activates or enhances the patient’s immune system to recognize and eliminate tumor cells. It offers advantages such as more durable therapeutic effects and relatively fewer toxic side effects. The main approaches to lung cancer immunotherapy include immune checkpoint inhibitors, tumor-specific antigen-targeted therapies, adoptive cell therapies, cancer vaccines, and oncolytic virus therapies. Among these, immune checkpoint inhibitors and tumor-specific antigen-targeted therapies have received approval from the U.S. Food and Drug Administration (FDA) for clinical use in lung cancer, significantly improving outcomes for patients with advanced non-small cell lung cancer. Although other immunotherapy strategies are still in clinical trials, they show great potential in improving treatment precision and efficacy. This article systematically reviews the latest research progress in lung cancer immunotherapy, including the development of novel immune checkpoint molecules, optimization of treatment strategies, identification of predictive biomarkers, and findings from recent clinical trials. It also discusses the current challenges in the field and outlines future directions, such as the development of next-generation immunotherapeutic agents, exploration of more effective combination regimens, and the establishment of precise efficacy prediction systems. The aim is to provide a valuable reference for the continued advancement of lung cancer immunotherapy.

Under the background of carbon peaking and carbon neutrality goals, the Ministry of Ecology and Environment, together with 15 national ministries and commissions, has formulated the Implementation Plan on Establishing a Carbon Footprint Management System, and it is urgent for traditional Chinese medicine(TCM) pharmaceutical enterprises to carry out research on carbon footprint accounting methods of related products. Based on the life cycle assessment(LCA) theory, taking mulberry leaf extract produced by a certain enterprise as an example, this study analyzed the carbon footprint of TCM extracts during the life cycle. The results show that for every 1 kg of product produced, the carbon emissions from the stages of raw material acquisition, transportation, and extract production are-20.569, 1.205, and 173.577 kgCO_2eq(CO_2 equivalent), respectively. The carbon footprint of the product is 154.213 kgCO_2eq·kg~(-1). In addition, the carbon emission is the highest in the production stage, in which the consumption of ethanol solvents makes the greatest contribution to the carbon footprint, accounting for 25.71%, more than one-fourth of the total carbon footprint. The second contribution was from the treatment process of TCM residues, accounting for 19.67%, closely followed by wastewater treatment(17.71%), the consumption of hot steam(17.43%), and drinking water(16.90%). The consumption of electric power and packaging materials has a smaller carbon emission of 2.58%. In particular, the carbon emission caused by the consumption of packaging materials is only 0.04%, which is negligible. The results of the study are expected to provide a reference for TCM enterprises to carry out research on the carbon footprint of products, offer ideas for collaborative innovation in reducing pollution and carbon emissions throughout the entire industry chain of TCM, and develop new quality productivity of modern TCM industry based on green and low-carbon manufacturing.
Morus/chemistry* ; Plant Leaves/chemistry* ; Carbon Footprint ; Drugs, Chinese Herbal/chemistry* ; Plant Extracts/analysis* ; Medicine, Chinese Traditional

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

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*

This study investigated the potential pathogenicity and genetic characteristics of ST314 Salmonella Kentucky(S.Ken-tucky)isolates from a broiler slaughterhouse.Antimicrobial susceptibility testing and whole-genome sequencing(WGS)were used to determine antimicrobial resistance,virulence factors,and the presence of antimicrobial resistance genes(ARGs)and mobile genetic elements(MGEs)among the isolates.The three multidrug resistant(MDR)isolates exhibited high resistance to multiple antimicrobial agents.The F4-2S strain exhibited resistance to 14 drugs across seven categories,whereas the F4T strain showed resistance to 13 drugs in the same number of categories.In contrast,the Y23 strain was resistant to nine drugs in six categories.Notably,F4-2S dem-onstrated high homology with F4T:both possessed 13 ARGs distributed across nine categories,in addition to a wide range of virulence factors,including secretion systems and effector proteins.The presence of IncR and IncX1 plasmids significantly enhanced both the antimicrobial resistance and pathogenicity of the isolates.The genome map of Y23 revealed a chromosome alongside two plasmids.The chromosome containedonly one resistance gene but several virulence factors,including the type III secretion system(T3SS),which is crucial for bacterial invasion.The plasmid pY23-1 contained eight types of 19 ARGs.Comparative analysis indicated that pY23-1 ex-hibited high homology with pZ1323SSL0055 and pSAL-045,all of which contained multiple ARGs,thus suggesting critical roles of these genes in the evolution of bacterial resistance.In conclusion,ST314 S.Kentucky demonstrated a complex mechanism of resis-tance coupled with significant pathogenic potential.The ARGs and MGEs in the plasmid contributed to the emergence and dissemina-tion of antimicrobial resistance.The multiple virulence factors present in the chromosome may be key factors driving the increasing virulence of ST314 S.Kentucky.

An analysis of 24 144 norovirus sequences from Asia and Russia deposited in GenBank between 1995 and 2023 was conducted,to understand the temporal and spatial variations in norovirus genotypes in these regions.Norovirus sequences from Asia and Russia were downloaded in FASTA format from GenBank for the years 1995-2023,and analyzed in Excel,R language,and GraphPad Prism for data visualization.The number of norovirus sequences submitted to GenBank increased annually from 2004 and peaked in 2015.Notably,China and Japan contributed 62.3％of all submitted norovirus sequences.These sequences encompassed 31 capsid genotypes(C-type),with GⅠ accounting for 9％and GⅡ accounting for 90％.Additionally,49 polymerase types(P-type)were identified,along with 68 combinations of CP types;among the analyzed recombinant sequences(4 460 entries in total),approxi-mately 41％belonged to three predominant recombinant strains:GⅡ.2[P16],GⅡ.4[P31],and GⅡ.4[P16].This analysis provides valuable insights into the distribution characteristics of norovirus genotypes across Asia and Russia over time,thereby supporting vac-cine design and evaluation efforts.

Microphthalmos is a congenital ocular developmental anomaly that manifests as a significant reduction in the size of eyes,and is often combined with various ocular disorders such as cataract.Due to its special intraocular anatomical features,the risk of intraoperative and postoperative complications of cataract surgery in microphthalmos is usually high.Combined with subscleral sclerectomy,peripheral iridectomy,and anterior segment vitrectomy,the incidence of the pre-existing complications in cataract surgery has decreased,meanwhile,the additional procedures may also bring new complications.In-depth understanding of the research progress of cataract surgery in microphthalmos and the prevention of complications is of great guiding significance to improve surgical outcomes,and can reduce the incidence of postoperative complications such as uveal effusion syndrome,secondary glaucoma and corneal edema,and promote personalized treatments for microphthalmos patients who suffered from cataract.

Aim To verify the mechanism of action of Carthami Flos-Lycopodii Herba in treating KOA carti-lage inflammation based on network pharmacology and in vitro and in vivo experiments.Methods The effec-tive ingredients of Carthami Flos-Lycopodii Herba were screened through the database,the core targets of"drug disease"were analyzed,and pathway enrichment analy-sis and molecular docking verification were conducted.Experimental verification:Primary chondrocytes were extracted from mice and divided into the control group,IL-1β group,treatment group,and treatment+TLR4 agonist group.CCK-8 method was used to screen the optimal intervention concentration of Carthami Flos-Ly-copodii Herba.ELISA was used to detect the content of inflammatory factors in chondrocytes.Western blot was employed to detect the protein expression related to cellular pathways.Subsequently,a KOA mouse model was constructed using the DMM method.After admin-istration,the knee joint injury of mice was evaluated u-sing safranin O-green staining.ELISA was used to de-tect the levels of inflammatory factors in serum.West-ern blot was employed to detect collagen Ⅱ,MMP13,Aggrecan,and apoptosis related protein expression in cartilage tissue.TUNEL staining was used to detect the apoptosis rate of cells.Results A total of 26 active ingredients of Carthami Flos-Lycopodii Herba were screened,as well as 123 potential targets for treating KOA.The enrichment analysis results indicated that it mainly involved mechanisms such as Toll like receptors and cell apoptosis.The experimental results showed that Carthami Flos-Lycopodii Herba alleviated the in-flammatory response of chondrocytes and affected the expression of pathway related proteins.Compared with KOA mice,safflower stretched muscle grass could im-prove cartilage damage and reduce the concentration of serum inflammatory factors,regulate the expression of collagen Ⅱ,MMP13,Aggrecan,and apoptosis related proteins in cartilage tissue,and reduce the fluorescence intensity of TUNEL staining in the tissue.Conclusions Carthami Flos-Lycopodii Herba can improve KOA cartilage inflammation,and its mechanism may be relat-ed to the TLR4/MyD88/NF-κB signaling pathway.

This study was aimed at understanding the prevalence and drug resistance status of Salmonella of waterfowl ori-gin in the Guangdong region in the past decade,to guide prevention and control efforts.The drug-sensitive paper slide method was used to conduct drug susceptibility testing on 314 waterfowl-originating Salmonella strains isolated from 238 waterfowl farms in the Guangdong region from 2013 to 2023.The isolated Salmonella strains were most resistant to penicillin,amoxicil-lin,cefradine,and cefazolin in the β-lactam group;sulphadoxine dimethylpyrimidine in the sulphonamide group;and tetracy-cline in the tetracycline group.The resistance rates ranged from 73.57％to 89.49％.The highest sensitivity was observed to amikacin,gentamicin,and kanamycin in the aminoglycoside group,and norfloxacin in the quinolone group,with susceptibility rates all exceeding 50％.The 280 strains of Salmonella showed multi-drug resistance to six classes of antimicrobial drugs and high resistance(as much as 60.83％)to five drug classes.Correlation analysis revealed the highest correlations for florfenicol with gentamicin,and for amoxicillin with penicillin(r=0.650 for both),followed by gentamicin with kanamycin(r=0.620).Salmonella resistance in waterfowl in Guangdong Province was generally severe and showed a complex pattern of drug resist-ance.Detection of waterfowl pathogens should be strengthened to prevent the spread of drug-resistant bacteria and support ra-tional use of antibiotics.This work provides a reference for Salmonella prevention and control in waterfowl farms.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.