QiDongNing induces lung cancer cell apoptosis via triggering P53/DRP1-mediated mitochondrial fission.

Non-small-cell lung cancer (NSCLC) is a major cause of worldwide cancer death, posing a challenge for effective treatment. Our previous findings showed that Chinese herbal medicine (CHM) QiDongNing (QDN) could upregulate the expression of p53 and trigger cell apoptosis in NSCLC. Here, our objective was to investigate the mechanisms of QDN-induced apoptosis enhancement. We chose A549 and NCI-H460 cells for validation in vitro, and LLC cells were applied to form a subcutaneous transplantation tumour model for validation in more depth. Our findings indicated that QDN inhibited multiple biological behaviours, including cell proliferation, cloning, migration, invasion and induction of apoptosis. We further discovered that QDN increased the pro-apoptotic BAX while inhibiting the anti-apoptotic Bcl2. QDN therapy led to a decline in adenosine triphosphate (ATP) and a rise in reactive oxygen species (ROS). Furthermore, QDN elevated the levels of the tumour suppressor p53 and the mitochondrial division factor DRP1 and FIS1, and decreased the mitochondrial fusion molecules MFN1, MFN2, and OPA1. The results were further verified by rescue experiments, the p53 inhibitor Pifithrin-α and the mitochondrial division inhibitor Mdivi1 partially inhibited QDN-induced apoptosis and mitochondrial dysfunction, whereas overexpression of p53 rather increased the efficacy of the therapy. Additionally, QDN inhibited tumour growth with acceptable safety in vivo. In conclusion, QDN induced apoptosis via triggering p53/DRP1-mediated mitochondrial fission in NSCLC cells.

circUBE3C modulates myoblast development by binding to miR-191 and upregulating the expression of p27.

Noncoding RNAs, including miRNAs (microRNAs) and circRNAs (circular RNA), are crucial regulators of myoblast proliferation and differentiation during muscle development. However, the specific roles and molecular mechanisms of circRNAs in muscle development remain poorly understood. Based on the existing circRNA-miRNA-mRNA network, our study focuses on circUBE3C, exploring its differential expression in fetal and adult muscle tissue of the cattle and investigating its impact on myoblast proliferation, apoptosis, and differentiation. The functional analysis of overexpression plasmids and siRNAs (small interfering RNAs) targeting circUBE3C was comprehensively evaluated by employing an array of advanced assays, encompassing CCK-8 (cell counting kit-8), EdU (5-ethynyl-20-deoxyuridine), flow cytometry, western blot analysis, and RT-qPCR. In vivo investigations indicated that overexpression of circUBE3C impedes the process of skeletal muscle regeneration. Mechanistically, we demonstrated that circUBE3C interacts with miR-191 and alleviates the suppression of p27 through cytoplasmic separation, bioinformatics prediction, dual-luciferase reporter assay, and RIP (RNA immunoprecipitation). Our findings indicate that the novel circRNA circUBE3C competitively binds to miR-191, thereby inhibiting proliferation and promoting apoptosis in bovine primary myoblasts and unveiling a regulatory pathway in bovine skeletal muscle development. These findings expand our understanding of circRNA functions in mammals and provide a basis for further exploration of their role in myogenesis and muscle diseases.

Targeting tumour surface collage with hydrogel probe: a new strategy to enhance intraoperative imaging sensitivity and stability of bladder cancer.

PURPOSE: The incomplete resection of non-muscle invasive bladder cancer (NMIBC) augments the risk of disease recurrence. Imaging-guided surgery by molecular probes represents a pivotal strategy for mitigating postoperative recurrence. Traditional optical molecular probes, primarily composed of antibodies/peptides targeting tumour cells and fluorescent groups, are challenged by the high heterogeneity of NMIBC cells, leading to inadequate probe sensitivity. We have developed a collagen-adhesive probe (CA-P) to target the collagen within the tumour microenvironment, aiming to address the issue of insufficient imaging sensitivity. METHODS: The distribution characteristics of collagen in animal bladder cancer models and human bladder cancer tissues were explored. The synthesis and properties of CA-P were validated. In animal models, the imaging performance of CA-P was tested and compared with our previously reported near-infrared probe PLSWT7-DMI. The clinical translational potential of CA-P was assessed using human ex vivo bladder tissues. RESULTS: The distribution of collagen on the surface of tumour cells is distinct from its expression in normal urothelium. In vitro studies have demonstrated the ability of the CA-P to undergo a "sol-gel" transition upon interaction with collagen. In animal models and human ex vivo bladder specimens, CA-P exhibits superior imaging performance compared to PLSWT7-DMI. The sensitivity of this probe is 94.1%, with a specificity of 81%. CONCLUSION: CA-P demonstrates the capability to overcome tumour cell heterogeneity and enhance imaging sensitivity, exhibiting favorable imaging outcomes in preclinical models. These findings provide a theoretical basis for the application of CA-P in intraoperative navigation for NMIBC.

Laser Direct Writing of Flexible Thermal Flow Sensors.

Thin film-based thermal flow sensors afford applications in healthcare and industries owing to their merits in preserving initial flow distributions. However, traditional thermal flow sensors are primarily applied to track flow intensities based on hot-wire or hot-film sensing mechanisms due to their relatively facile device configurations and fabrication strategies. Herein, a calorimetric thermal flow sensor is proposed based on laser direct writing to form laser-induced graphene as heaters and temperature sensors, resulting in monitoring both flow intensities and orientations. Via homogeneously surrounding spiral heaters with multiple temperature sensors, the device exhibits high sensitivity (∼162 K·s/m) at small flows with an extended flow detection range (∼25 m/s). Integrating the device with a data-acquisition board and a dual-mode graphical user interface enables wirelessly and dynamically monitoring respiration and the motion of robotic arms. This versatile flow sensor with facile manufacturing affords potentials in health inspection, remote monitoring, and studying hydrodynamics.

Regulation of Mycobacterium biofilm development and novel measures against antibiotics resistance.

Currently, there are over 170 recognized species of Mycobacterium, the only genus in the family Mycobacteriaceae. Organisms belonging to this genus are quite diverse with respect to their ability to cause disease in humans. The Mycobacterium genus includes human pathogens (Mycobacterium tuberculosis complex and Mycobacterium leprae) and environmental microorganisms known as non-tuberculosis mycobacteria (NTM). A common pathogenic factor of Mycobacterium is the formation of biofilms. Bacterial biofilms are usually defined as bacterial communities attached to the surface, and are also considered as shared spaces of encapsulated microbial cells, including various extracellular polymeric substrates (EPS), such as polysaccharides, proteins, amyloid proteins, lipids, and extracellular DNA (EDNA), as well as membrane vesicles and humic like microorganisms derived refractory substances. The assembly and dynamics of the matrix are mainly coordinated by second messengers, signaling molecules, or small RNAs. Fully deciphering how bacteria provide structure for the matrix, thereby promoting extracellular reactions and benefiting from them, remains a challenge for future biofilm research. This review introduces a five step development model for biofilms and a new model for biofilm formation, analyses the pathogenicity of biofilms, their interactions with bacteriophages and host immune cells, and the key genes and regulatory networks of mycobacterial biofilms, as well as mycobacterial biofilms and drug resistance, in order to provide a basis for clinical treatment of diseases caused by biofilms.

Associations between vision impairment and multimorbidity among older Chinese adults: results from the China health and retirement longitudinal study.

BACKGROUND: Although several studies have reported the relationship between vision impairment (VI) and multimorbidity in high-income countries, this relationship has not been reported in low- and middle-income countries. This study aimed to explore the relationship between VI with multimorbidity and chronic conditions among the elderly Chinese population. METHODS: The cross-sectional analysis was applied to data from the China Health and Retirement Longitudinal Study (CHARLS) in 2018. A total of 8,108 participants ≥ 60 years old were included, and 15 chronic conditions were used in this study. Logistic regression analysis was used to analyze the relationship between VI with multimorbidity and chronic conditions. RESULTS: The prevalence of 15 chronic conditions and multimorbidity was higher among the elderly with VI than those without VI. After adjusting for demographic and socioeconomic confounders, 10 chronic conditions were associated with VI (all P < 0.05). Furthermore, positive association was observed between VI and one (odds ratio [OR]: 1.52; 95% confidence intervals [95%CI]: 1.16-2.00; P = 0.002), two (OR: 2.09; 95%CI: 1.61-2.71; P < 0.001), three (OR: 2.87; 95%CI: 2.22-3.72; P < 0.001), four (OR: 3.60; 95%CI: 2.77-4.69; P < 0.001), and five or more (OR: 5.53; 95%CI: 4.32-7.09; P < 0.001) chronic conditions, and the association increased as the number of chronic conditions (P for trend < 0.001). Sensitivity analysis stratified by gender, education, smoking status, and annual per capita household expenditure still found VI to be positively associated with multimorbidity. CONCLUSIONS: For patients older than 60 years, VI was independently associated with multimorbidity and various chronic conditions. This result has important implications for healthcare resource plans and clinical practice, for example, increased diabetes and kidney function screening for patients with VI.

Copy number variation of bovine S100A7 as a positional candidate affected body measurements.

Beef production is closely related to the national economy and the attention has been paid to the improvement of beef cattle by molecular markers associated. Copy number variations (CNVs) recently have been gained many researches and recognized as an important source of genetic variation. Extensive studies have indicated that CNVs have effects on a large range of economic traits by a wide range of gene copy number alteration. S100A7 is a member of S100 family which is a famous family of Ca2+-binding proteins. S100A7 plays a crucial role in many important phenotypes (progress) including inflammatory diseases, psoriasis, obesity, etc. The aim of our study was to explore the phenotypic effects of CNV located in the S100A7 gene of bovine chromosome 3. We detected S100A7 CNV by qPCR in different cattle breeds, including Qinchuan cattle, Yunling cattle, Xianan cattle and a crossbred group Pinan. The copy number was identified as gain, normal and loss type, our results showed that the gain type was the main type in three types of S100A7 CNV of the whole tested breeds. After CNV detection, association analysis between S100A7 CNV and growth traits was carried out in four cattle breeds. We found significant effects of the CNV on cattle growth traits with differently preferred CNV types such as gain type with better chest depth (p = 0.043) in QC, loss type with better body length (p = 0.008) and rump width (p = 0.014) in YL, normal with better chest girth (p = 0.001), gain with better waist width (p = 0.001) and rump width (p = 0.044) in PN. These results suggested that the S100A7 CNV could affect the phenotypic traits and be used as a promising genetic marker for cattle molecular breeding.

Insertion/deletions within the bovine FoxO1 gene and their association analysis with growth traits in three Chinese cattle breeds.

FOXO1 (FKHR) gene, as a transcription factor, plays a vital role in animal growth and development, participating in many biological processes. The aim of this study was to ascertain Insertion/deletions (Indels) polymorphism within bovine FoxO1 gene in 679 Chinese adult cows and associate them with stature traits. Two Indels (named as Indel-3 and Indel-4, recorded as rs383545622 and rs525318770 in NCBI, respectively) were successfully genotyped by the Once PCR method, which was reliable, rapid and cost effective for simultaneous detection of two or more Indels. Indel-3 and Indel-4 were located at the second intron. All four different haplotypes (H1: D3D4, H2: I3D4, H3: D3I4, H4: I3I4) could be identified, and the D (del-) allele, DD (del-/del-) genotype and D3D4 haplotype retained the highest frequency. However, individuals with DI (D3I3, D4I4 or H1H4/H2H3 genotype) showed significantly better phenotypic traits than those with the other genotypes in Nanyang cattle, showing a hybrid vigor. The results implied that this DI genotype can be applied to early selective breeding to improve the productivity of Nanyang cattle. Our results suggested that these two Indels within the bovine FoxO1 gene might be used as genetic markers for marker-assisted selection (MAS) in cattle breeding and genetics.

Gas Chromatography-Mass Spectrometry-Based Cerebrospinal Fluid Metabolomics to Reveal the Protection of Coptisine against Transient Focal Cerebral Ischemia-Reperfusion Injury via Anti-Inflammation and Antioxidant.

Coptisine (Cop) exerts a neuroprotective effect on central nervous system disease, particularly ischemic stroke. However, its protective mechanism is still unclear. This study aimed to investigate the protective effect of Cop on cerebral ischemia-reperfusion (IR) rats with a middle cerebral artery occlusion model by integrating a gas chromatography-mass spectrometry (GC-MS)-based metabolomics approach with biochemical assessment. Our results showed that Cop could improve neurobehavioral function and decrease the ischemia size in IR rats. In addition, Cop was found to decrease inflammatory mediators (e.g., prostaglandin D2 (PGD2) and tumor necrosis factor-α (TNF-α) and attenuate oxidative stress response (e.g., increase the superoxide dismutase (SOD) expression and decrease 8-iso-PGF2α level). Furthermore, the GC-MS-based cerebrospinal fluid (CSF) metabolomics analysis indicated that Cop influenced the level of glycine, 2,3,4-trihydroxybutyric acid, oleic acid, glycerol, and ribose during IR injury. Cop exhibited a good neuroprotective effect against cerebral IR injury and metabolic alterations, which might be mediated through its antioxidant and anti-inflammatory properties.

USP18-mediated protein deISGylation and its role in tuberculosis and other infectious diseases.

The transcription of interferon-stimulated gene 15 (isg15) is induced by type I interferons. ISG15 can covalently modify target proteins through the sequential action of enzymesE1, E2, and E3, a process known as ISGylation. The ISGylation of host proteins is widely involved in immune responses, such as host antiviral defence. Ubiquitin-specific protease 18 (USP18), as a deubiquitinase (DUB), can remove ISG15 conjugated to target proteins and inhibit host immune responses by suppressing the type I interferon signaling. The dynamic balance between ISGylation and deISGylation mediated by ISG15 or USP18 respectively plays a significant role in the tuberculosis. Furthermore, similar to ISG15, USP18 is extensively involved in virus-host interaction. In this review, we summarize the roles of ISGylation and deISGylation in tuberculosis and other important diseases mediated by ISG15 and USP18 respectively, underlying regulator network. Further studies in this aspect will inspire new host-targeted strategies to control important diseases such as tuberculosis.

Deletions in GSN gene associated with growth traits of four Chinese cattle breeds.

The aim of this study was to assess the potential of 21 bp mutation in the second intron of the GSN gene as a molecular marker-assisted by exploring the effect of 21 bp mutation on growth traits in four beef cattle breeds. Gelsolin (GSN), a member of the superfamily of gel proteins, is involved in the regulation of a variety of cellular activities in the organism and plays an important function in cell motility, apoptosis, signal transduction and inflammatory responses. Gelatin can not only negatively regulate the pro-apoptotic effect of P53 protein, but also promote apoptosis by blocking the interaction between actin and deoxyribonuclease, so, the GSN gene was selected as a candidate gene in this study. In this study, a 21 bp mutation on the second intron to the GSN gene was verified in 573 individuals of Yunling (YL, n = 220), Jiaxian (JX, n = 140), Xianan (XN, n = 114) and Qinchuan (QC, n = 97) cattle breeds using Once PCR and agarose gel electrophoresis. The association analysis of polymorphisms in the GSN gene with growth traits in four breeds was revealed: in YL cattle, the heart girth and forehead size of heterozygous ID genotype were significantly higher than II genotype (P < 0.05). In JX cattle, the withers height, body length and heart girth of II and ID genotype were significantly highest than DD genotype (P < 0.01); the height at hip cross and height at sacrum of II genotype was significantly highest than DD genotype (P < 0.01), but ID genotype was significantly higher than DD genotype. In XN cattle, the abdominal girth and circumference of the cannon bone of II genotype were significantly higher than ID genotype (P < 0.05). In QC cattle, the hucklebone width of ID genotype was significantly the highest than II genotype (P < 0.01). The results suggest that GSN may be an important candidate gene and that a 21 bp mutation on the second intron to the GSN gene can be used for molecular marker-assisted selection of four beef cattle breeds.

Recent progress in the optical detection of pathogenic bacteria based on noble metal nanoparticles.

Pathogenic bacteria have become a huge threat to social health and economy for their frighteningly infectious and lethal capacity. It is quite important to make a diagnosis in advance to prevent infection or allow a rapid treatment after infection. Noble metal nanoparticles, due to their unique physicochemical properties, especially optical properties, have drawn a great attention during the past decades and have been widely applied into all kinds of fields related to human health. By utilizing these noble metal nanoparticles, optical diagnosis platforms towards pathogenic bacteria have emerged continually, providing highly sensitive, selective, and particularly facile detection tools for clinic or point-of-care diagnosis. This review summarizes the recent development in this field. It begins with a brief introduction of pathogenic bacteria and noble metal nanoparticles. And then, optical detection methods are systematically discussed in three distinct aspects. In addition to these proof-of-concept methods, corresponding algorithms and point-of-care detection devices are also described. Finally, the review ends up with subjective views on present limitations and some appropriate advice for future research directions.

Coptisine protects against transient focal cerebral ischaemic injury by regulation of arachidonic acid metabolism.

OBJECTIVES: Coptisine (Cop), an alkaloid isolated from Rhizoma Coptidis, has a protective effect against central nervous system diseases such as cerebral ischaemia-reperfusion (IR). Dysregulations in fatty acids metabolism are associated with neuroprotection and neuroinflammation. However, the effect of Cop on fatty acids metabolomics during anti-IR remains unclear. METHODS: Cerebral IR rats were established by middle cerebral artery occlusion, and the therapeutic effect of Cop was evaluated by 2, 3, 5-triphenytetrazolium chloride staining and neurological deficits scores. By liquid chromatography-tandem mass spectrometry (LC-MS/MS), fatty acids metabolomics analysis in ischaemic hemisphere and serum were investigated. RESULTS: We observed Cop (2 mg/kg/qd) was able to reduce cerebral infarct size and ameliorate the neurological function score. Meanwhile decrease in tumour necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) after Cop treatment. Compared with control, down-regulation of cyclopentenone PGs (e.g., PGA2, PGJ2, and 15-deoxy- delta-12,14-PGJ2) was observed in cerebral IR, but upregulation of them when followed by Cop treatment. Similarly, we found the ratios of 14,15-dihydroxyeicosatrienoic acid(14,15-DHET)/arachidonic acid and 11,12-DHET/arachidonic acid was lower in cerebral IR injury relative to control, while their ratios were increased after Cop treatment. CONCLUSION: Our results indicated that Cop protect against cerebral IR injury, and its mechanism might be closely associated with antiinflammation and the regulation of arachidonic acid metabolism.

Gut microbiota influence on lung cancer risk through blood metabolite mediation: from a comprehensive Mendelian randomization analysis and genetic analysis.

Background: Gut microbiota (GM) and metabolic alterations play pivotal roles in lung cancer (LC) development and host genetic variations are known to contribute to LC susceptibility by modulating the GM. However, the causal links among GM, metabolite, host genes, and LC remain to be fully delineated. Method: Through bidirectional MR analyses, we examined the causal links between GM and LC, and utilized two-step mediation analysis to identify potential mediating blood metabolite. We employed diverse MR methods, including inverse-variance-weighted (IVW), weighted median, MR-Egger, weighted mode, and simple mode, to ensure a robust examination of the data. MR-Egger intercept test, Radial MR, MR-PRESSO, Cochran Q test and Leave-one-out (LOO) analysis were used for sensitivity analyses. Analyses were adjusted for smoking, alcohol intake frequency and air pollution. Linkage disequilibrium score regression and Steiger test were used to probe genetic causality. The study also explored the association between specific host genes and the abundance of gut microbes in LC patients. Results: The presence of Bacteroides clarus was associated with an increased risk of LC (odds ratio [OR] = 1.07, 95% confidence interval [CI]: 1.03-1.11, p = 0.012), whereas the Eubacteriaceae showed a protective effect (OR = 0.82, 95% CI: 0.75-0.89, p = 0.001). These findings remained robust after False Discovery Rate (FDR) correction. Our mediator screening identified 13 blood metabolites that significantly influence LC risk after FDR correction, underscoring cystine and propionylcarnitine in reducing LC risk, while linking specific lipids and hydroxy acids to an increased risk. Our two-step mediation analysis demonstrated that the association between the bacterial pathway of synthesis of guanosine ribonucleotides and LC was mediated by Fructosyllysine, with mediated proportions of 11.38% (p = 0.037). LDSC analysis confirmed the robustness of these associations. Our study unveiled significant host genes ROBO2 may influence the abundance of pathogenic gut microbes in LC patients. Metabolic pathway analysis revealed glutathione metabolism and glutamate metabolism are the pathways most enriched with significant metabolites related to LC. Conclusion: These findings underscore the importance of GM in the development of LC, with metabolites partly mediating this effect, and provide dietary and lifestyle recommendations for high-risk lung cancer populations.

Clinical Efficacy and Gut Microbiota Regulating-Related Effect of Si-Jun-Zi Decoction in Postoperative Non-Small Cell Lung Cancer Patients: A Prospective Observational Study.

BACKGROUND: Postoperative non-small cell lung cancer (NSCLC) patients frequently encounter a deteriorated quality of life (QOL), disturbed immune response, and disordered homeostasis. Si-Jun-Zi Decoction (SJZD), a well-known traditional Chinese herbal formula, is frequently employed in clinical application for many years. Exploration is underway to investigate the potential therapeutic effect of SJZD for treating postoperative NSCLC. OBJECTIVE: To assess the efficacy of SJZD on QOLs, hematological parameters, and regulations of gut microbiota in postoperative NSCLC patients. METHODS: A prospective observational cohort study was conducted, enrolling 65 postoperative NSCLC patients between May 10, 2020 and March 15, 2021 in Yueyang Hospital, with 33 patients in SJZD group and 32 patients in control (CON) group. The SJZD group comprised of patients who received standard treatments and the SJZD decoction, while the CON group consisted of those only underwent standard treatments. The treatment period was 4 weeks. The primary outcome was QOL. The secondary outcomes involved serum immune cell and inflammation factor levels, safety, and alterations in gut microbiota. RESULTS: SJZD group showed significant enhancements in cognitive functioning (P = .048) at week 1 and physical functioning (P = .019) at week 4. Lung cancer-specific symptoms included dyspnea (P = .001), coughing (P = .008), hemoptysis (P = .034), peripheral neuropathy (P = .019), and pain (arm or shoulder, P = .020, other parts, P = .019) eased significantly in the fourth week. Anemia indicators such as red blood cell count (P = .003 at week 1, P = .029 at week 4) and hemoglobin (P = .016 at week 1, P = .048 at week 4) were significantly elevated by SJZD. SJZD upregulated blood cell cluster differentiation (CD)3+ (P = .001 at week 1, P < .001 at week 4), CD3+CD4+ (P = .012 at week 1), CD3+CD8+ (P = .027 at week 1), CD19+ (P = .003 at week 4), increased anti-inflammatory interleukin (IL)-10 (P = .004 at week 1, P = .003 at week 4), and decreased pro-inflammatory IL-8 (P = .004 at week 1, p = .005 at week 4). Analysis of gut microbiota indicated that SJZD had a significant impact on increasing microbial abundance and diversity, enriching probiotic microbes, and regulating microbial biological functions. CONCLUSIONS: SJZD appears to be an effective and safe treatment for postoperative NSCLC patients. As a preliminary observational study, this study provides a foundation for further research.

Management of Nontraumatic Spontaneous Renal Hemorrhage (Wünderlich Syndrome) through Robotic-Assisted Laparoscopic Nephrectomy: A Case Series.

BACKGROUND Wünderlich syndrome (WS) is a rare diagnosis of nontraumatic spontaneous renal hemorrhage into the subcapsular, perirenal, or pararenal spaces. Prompt and effective intervention is necessary for an accurate pathological diagnosis and preservation of life. In the current literature, open surgery is the primary option when conservative treatment fails, but there can be serious trauma and corresponding consequences. Herein, we present 3 cases of Wünderlich syndrome managed by robot-assisted laparoscopic nephrectomy via a retroperitoneal approach. CASE REPORT Patient 1 was a 44-year-old woman with right flank pain for 6 h. Patient 2 was a 53-year-old woman with a history of diabetes who had pain in her right flank pain and nausea for 1 day. Patient 3 was a 45-year-old man with left flank pain for 1 day. All cases of WS were confirmed by CT. All 3 patients were treated with retroperitoneal robot-assisted nephrectomy after conservative treatment failed. Pathological examination confirmed that patient 1 had angiomyolipoma, and patients 2 and 3 had renal clear cell carcinoma. At the 9-month follow-up, renal function was good and no evidence of recurrence or metastasis has been detected. CONCLUSIONS These cases have highlighted the importance of the clinical history and imaging findings in the diagnosis of Wünderlich syndrome, and show that rapid management can be achieved using robot-assisted laparoscopic nephrectomy. However, it is crucial to have a skilled surgical team and adequate preoperative preparation.

Predicting the mechanism of action of YQYYJD prescription in the treatment of non-small cell lung cancer using transcriptomics analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: The efficacy of the herbal formula Yiqi Yangyin Jiedu (YQYYJD) in the treatment of advanced lung cancer has been reported in clinical trials. However, the key anti-lung cancer herbs and molecular mechanisms underlying its inhibition of lung cancer are not well-understood. AIM OF THE STUDY: To identify the key anti-lung cancer herbs in the YQYYJD formula and investigate their therapeutic effect and potential mechanism of action in non-small cell lung cancer (NSCLC) using transcriptomics and bioinformatics techniques. MATERIALS AND METHODS: A mouse Lewis lung carcinoma (LLC) subcutaneous inhibitory tumor model was established with 6 mice in each group. Mice were treated with the YQYYJD split formula: Yiqi Formula (YQ), Yangyin Formula (YY), and Ruanjian Jiedu Formula (RJJD) for 14 days. The tumor volume and mouse weight were recorded, and the status of tumor occurrence was further observed by taking photos. The tumor was stained with hematoxylin-eosin to observe its histopathological changes. Immunohistochemistry was used to detect the expression of the proliferation marker Ki67 and the apoptotic marker Caspase-3 in tumor tissues. Flow cytometry was used to detect the number of CD4+ and CD8+ T cells and cytokines interleukin-2 (IL-2) and interferon-gamma (IFN-γ) in the spleen and tumor tissues. The differential genes of key drugs against tumors were obtained by transcriptome sequencing of tumors. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) enrichment analyses were performed on differential genes to obtain pathways and biological processes where targets were aggregated. TIMER2.0 and TISIDB databases were used to evaluate the impact of drugs on immune cell infiltration and immune-related genes. The binding activity of the key targets and compounds was verified by molecular docking. RESULTS: YQ, YY, and RJJD inhibited the growth of subcutaneous transplanted tumors in LLC mice to varying degrees and achieved antitumor effects by inhibiting the expression of tumor cell proliferation, apoptosis, and metastasis-related proteins. Among the three disassembled prescriptions, YQ better inhibited the growth of subcutaneous transplanted tumors in LLC mice, significantly promoted tumor necrosis, significantly increased the expression of Caspase-3 protein in tumor tissue, and significantly decreased the expression of Ki-67 (P < 0.05), thereby increasing the infiltration of CD8+ T cells. YQ significantly increased the expression of CD4+ and CD8+ T cells in tumor and splenic tissues of tumor-bearing mice and up-regulated the expression of IL-2 and IFN-γ. Transcriptome sequencing and bioinformatics results showed that after YQ intervention, differentially expressed genes were enriched in more than one tumor-related pathway and multiple immune regulation-related biological functions. There were 12 key immune-related target genes. CONCLUSION: YQ was the key disassembled prescription of YQYYJD, exerting significant antitumor effects and immune regulation effects on NSCLC. It may have relieved T cell exhaustion and regulated the immune microenvironment to exert antitumor effects by changing lung cancer-related targets, pathways, and biological processes.

Dual roles of AtNBR1 in regulating selective autophagy via liquid-liquid phase separation and recognition of non-ubiquitinated substrates in Arabidopsis.

Selective macroautophagy/autophagy in metazoans involves the conserved receptors NBR1 and SQSTM1/p62. Both autophagy receptors manage ubiquitinated cargo recognition, while SQSTM1 has an additional, distinct role of facilitating liquid-liquid phase separation (LLPS) during autophagy. Given that plants lack SQSTM1, it is postulated that plant NBR1 may combine activities of both metazoan NBR1 and SQSTM1. However, the precise mechanism by which plant NBR1 recognizes non-ubiquitinated substrates and its ability to undergo LLPS during selective autophagy remain elusive. Here, we implicate both the ZZ-type zinc finger motif and the four-tryptophan domain of Arabidopsis NBR1 (AtNBR1) in the recognition of non-ubiquitinated cargo proteins. Additionally, we reveal that AtNBR1 indeed undergoes LLPS prior to ATG8-mediated autophagosome formation, crucial for heat stress resistance in Arabidopsis. Our findings unveil the dual roles of AtNBR1 in both cargo recognition and LLPS during plant autophagy and advance our understanding of NBR1-mediated autophagy in plants compared to metazoans.Abbreviations: ATG8: autophagy 8; Co-IP: co-immunoprecipitation; EXO70E2: exocyst subunit EXO70 family protein E2; FRAP: fluorescence recovery after photobleaching; FW domain: four-tryptophan domain; GFP: green fluorescent protein; HS: heat stress; LLPS: liquid-liquid phase separation; LIR: LC3-interacting region; NBR1: next to BRCA1 gene 1; PAS: phagophore assembly site; PB1 domain: Phox and Bem1 domain; RFP: red fluorescent protein; ROF1: rotamase FKBP 1; SARs: selective autophagy receptors; UBA domain: ubiquitin-associated domain; Y2H: yeast two-hybrid; ZZ domain: ZZ-type zinc finger motif domain.

Assessment of Causality Between Diet-Derived Antioxidants and Primary Open-Angle Glaucoma: A Mendelian Randomization Study.

Purpose: This study aimed to investigate the genetic causal relationships among diet-derived circulating antioxidants, primary open-angle glaucoma (POAG), and glaucoma-related traits using two-sample Mendelian randomization (MR). Methods: Genetic variants associated with diet-derived circulating antioxidants (retinol, ascorbate, ß-carotene, lycopene, α-tocopherol, and γ-tocopherol) were assessed as absolute and metabolic instrumental variables. POAG and glaucoma-related traits data were derived from a large, recently published genome-wide association study database; these traits included intraocular pressure (IOP), macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and vertical cup-to-disc ratio (vCDR). MR analyses were performed per outcome for each exposure. Results: We found no causal association between six diet-derived antioxidants and POAG using the International Glaucoma Genetics Consortium data. For absolute antioxidants, the odds ratios (ORs) ranged from 1.011 (95% confidence interval [CI], 0.854-1.199; P = 0.895) per natural log-transformed ß-carotene to 1.052 (95% CI, 0.911-1.215; P = 0.490) for 1 µmol/L of ascorbate. For antioxidant metabolites, the OR ranged from 0.998 (95% CI, 0.801-1.244; P = 0.989) for ascorbate to 1.210 (95% CI, 0.870-1.682; P = 0.257) for γ-tocopherol, using log-transformed levels. A similar result was obtained with the FinnGen Biobank. Furthermore, our results showed no significant genetic association between six diet-derived antioxidants and glaucoma-related traits. Conclusions: Our study did not support a causal association among six diet-derived circulating antioxidants, POAG, and glaucoma-related traits. This suggests that the intake of antioxidants may not have a preventive effect on POAG and offers no protection to retinal nerve cells. Translational Relevance: This study provides valid evidence regarding the use of diet-derived antioxidants for glaucoma patients.

Association of spouse's vision impairment with depressive symptoms and cognitive decline in partner: A nationally representative study in China.

BACKGROUND: Although several previous studies have reported on the relationship between vision impairment and caregiver mental health, mixed results were obtained, and only one study reported the association between spousal vision impairment and partner depression. Therefore, our study aimed to examine the association between spousal vision impairment and the partner's depressive symptoms and cognitive decline. METHODS: This cross-sectional study gathered baseline data from the China Health and Retirement Longitudinal Study (CHARLS) in 2011. A total of 10,956 couples were included in the study. Vision impairment was assessed by respondents' self-reported distance or near vision. Multivariate logistic and linear regression were conducted to evaluate the association between the spouse's vision impairment and the partner's depressive symptoms and cognitive function. RESULTS: The prevalence of partners with depressive symptoms was significantly higher among spouses with vision impairment than among those without (43.3 % vs. 32.5 %; P < 0.001), and cognitive function was significantly lower (spousal vision impairment 14.4 ± 4.5 vs. no spousal vision impairment 15.5 ± 4.6; P < 0.001). After fully adjusting for potential confounders, the partner had greater odds of depressive symptoms for spouses with vision impairment than for those without (odds ratio: 1.525; 95 % confidence interval [CI]: 1.387 to 1.677). Furthermore, spousal vision impairment was negatively associated with the partner's cognitive function (ß = -0.640; 95 % CI: -0.840 to -0.440). Sensitivity analysis was performed, and consistent results were obtained (all P < 0.05). LIMITATIONS: Visual function was assessed by self-reporting. CONCLUSIONS: A spouse's vision impairment is associated with depressive symptoms and cognitive decline in the partner. The findings imply the importance of considering the partner's mental health when managing their spouse's vision impairment.