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Background: Preoperative immune-inflammatory condition influencing the metabolism of malignancies. We sought to investigate the prognostic value of a novel immune-inflammatory metabolic marker, the monocyte-to-high-density lipoprotein ratio (MHR), in patients with locally advanced pancreatic cancer. Methods: A retrospective analysis was conducted on the clinical data of 118 patients with locally advanced pancreatic cancer and obstructive jaundice who underwent allogeneic vascular replacement pancreaticoduodenectomy in our hospital from Apr. 2011 to Dec. 2023. To assess the predictive capacity of immune-inflammatory metabolic marker, we utilized the area under the receiver operating characteristic curve (AUC-ROC) and assessed the predictive potential of MHR in forecasting outcomes through both univariate and multivariate Cox proportional hazard analyses. Results: The area under AUC for MHR in predicting 1-year postoperative survival was 0.714, with an optimal cutoff value of 1.184, yielding a sensitivity of 78.9% and specificity of 66.2%. Based on this cutoff value, patients were divided into a low MHR group (MHR ≤1.184, n = 61) and a high MHR group (MHR >1.184, n = 57). The median survival times for the low and high MHR groups were 27.0 months and 12.0 months, respectively (χ2 = 30.575, p < 0.001), and the median DFS were 18.0 months and 8.0 months, respectively (χ2 = 26.330, p < 0.001). Univariate and multivariate analyses indicated that preoperative MHR, preoperative creatinine, operation duration, and TNM stage were independent predictors of postoperative mortality, while preoperative MHR, preoperative creatinine, and TNM stage were independent predictors of postoperative recurrence risk. Conclusion: MHR, as an independent immune-inflammatory metabolic predictor of OS and DFS in patients with advanced PC after pancreaticoduodenectomy. Early monitoring and reduction of MHR may be of great significance in improving prognosis.

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Background: The nutritional status and coagulation function of peritoneal dialysis (PD) patients are closely associated with their prognosis. This study aims to investigate the prognostic value of the albumin-to-fibrinogen ratio (AFR) on mortality in PD patients and to establish a prognostic prediction model based on AFR. Methods: We retrospectively collected data from 148 PD patients treated at our hospital between Oct. 2011 and Dec. 2021. Using the "survminer" package in R, we determined the optimal cutoff value for AFR and divided the patients into low-AFR and high-AFR groups. The primary endpoint of this study was overall survival (OS). Univariate and multivariate Cox analyses were used to assess the impact of AFR and other factors on prognosis, and a corresponding prognostic prediction model was constructed using a nomogram, which was evaluated through ROC curves, the c-index, and calibration plots. Results: The optimal cutoff value for AFR was 9.06. In the entire cohort, 30 patients (20.2%) were classified into the low-AFR group. Compared to the high-AFR group, patients in the low-AFR group were older, had lower total urine output over 24 h, higher blood urea nitrogen, higher total protein and urinary microalbumin levels, and longer remission times (p < 0.05). They also had a poorer OS (HR: 1.824, 95%CI: 1.282-2.594, p < 0.05). Multivariate Cox analysis indicated that AFR was an independent prognostic factor for OS (HR: 1.824, 95% CI: 1.282-2.594, p < 0.05). A prognostic prediction model based on AFR, age, and cause of ESRD was successfully validated for predicting OS in PD patients. Conclusion: AFR represents a potential prognostic biomarker for PD patients. The prognostic prediction model based on AFR can provide accurate OS predictions for PD patients, aiding clinicians in making better-informed decisions.

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In this editorial, we comment on the article by Cao et al. Through applying isobaric tags for relative and absolute quantification technology coupled with liquid chromatography-tandem mass spectrometry, the researchers observed significant differential expression of 47 proteins when comparing serum samples from pregnant women with gestational diabetes mellitus (GDM) to the healthy ones. GDM symptoms may involve abnormalities in inflammatory response, complement system, coagulation cascade activation, and lipid metabolism. Retinol binding protein 4 and angiopoietin like 8 are potential early indicators of GDM. GDM stands out as one of the most prevalent metabolic complications during pregnancy and is linked to severe maternal and fetal outcomes like pre-eclampsia and stillbirth. Nevertheless, none of the biomarkers discovered so far have demonstrated effectiveness in predicting GDM. Our topic was designed to foster insights into advances in the application of proteomics for early prenatal screening of GDM.

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AIM: To investigate the current situation and influencing factors of self-management ability in dry eye patients in west China. METHODS: A total of 265 patients clinically diagnosed with dry eye received a convenience survey questionnaire at West China Hospital of Sichuan University. All participants completed the rating scale of health self-management skill for adults (AHSMSRS), Huaxi Emotional-Distress Index (HEI), e-health literacy scale (e-HEALS) and Brief Illness Perception Questionnaire (Brief-IPQ). A generalized linear model was employed to establish a multivariate linear model with demographic data, psychological state, e-HEALS, and illness perception as independent variables and health self-management skill score as the dependent variable. RESULTS: The mean score for health self-management skill was 165.58±15.79. Multivariate analysis revealed that advanced age, better illness perception and improved psychological state were associated with better health self-management ability among dry eye patients. Furthermore, the health self-management ability of patients with a disease duration less than 1y was found to be higher compared to those with a disease duration exceeding 1y. CONCLUSION: The health self-management ability of dry eye patients in west China is relatively high. Age, duration of disease, illness perception and psychological state are the influencing factors on the health self-management ability of dry eye patients.

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There is no definitive approach for assessing mesenteric ischemia and determining the optimal timing for endovascular intervention in the management of spontaneous isolated dissection of the superior mesenteric artery (SISMAD). A 56-year-old male with acute abdominal pain was diagnosed with SISMAD. After evaluating mesenteric ischemia through mesenteric fractional flow reserve (FFR), FFR was 0.72, and the patient was recommended conservative treatment for SISMAD, which involves fasting, total parenteral nutrition, and anticoagulation. The patient's syndrome was relieved after conservative treatment for 14 days without stent implantation. Over the next 5 years, no recurrence of abdominal pain or worsening of SISMAD was observed in the patient. Assessing the severity of mesenteric ischemia can be done through mesenteric FFR. Upon confirmation of the exclusion of risks related to dilatation or rupture of SISMAD aneurysm, an approach in favor of conservative management for SISMAD may indeed be considered pragmatic when the FFR exceeds 0.72.

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Retinal degenerative diseases were a large group of diseases characterized by the primary death of retinal ganglion cells (RGCs). Recent studies had shown an interaction between autophagy and nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasomes, which may affect RGCs in retinal degenerative diseases. The NLRP3 inflammasome was a protein complex that, upon activation, produces caspase-1, mediating the apoptosis of retinal cells and promoting the occurrence and development of retinal degenerative diseases. Upregulated autophagy could inhibit NLRP3 inflammasome activation, while inhibited autophagy can promote NLRP3 inflammasome activation, which leaded to the accelerated emergence of drusen and lipofuscin deposition under the neurosensory retina. The activated NLRP3 inflammasome could further inhibit autophagy, thus forming a vicious cycle that accelerated the damage and death of RGCs. This review discussed the relationship between NLRP3 inflammasome and autophagy and its effects on RGCs in age-related macular degeneration, providing a new perspective and direction for the treatment of retinal diseases.

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BACKGROUND: Infectious diseases, such as COVID-19, are high-risk factors for delirium. However, the implementation of nonpharmacological interventions faces major challenges during an infectious disease pandemic. AIMS: To evaluate the effect of the nurse-led Hospital Elder Life Program (NL-HELP) on delirium reduction among delirious patients with COVID-19. DESIGN: A single-blind randomized clinical trial. METHODS: This study recruited 122 delirious patients with COVID-19 from internal medicine wards at West China Hospital in China between January 30 and March 31, 2023. Participants were randomized to the NL-HELP group (n = 62) or the usual care group (n = 60). Patients in the intervention group received the NL-HELP protocol three times daily for 7 days. Patients in the control group received usual care. The primary outcome was the absence/presence of delirium during the intervention period measured by the 3-min Diagnostic Confusion Assessment Method. RESULTS: Fewer patients remained delirious in the NL-HELP group than in the control group. There were significantly more delirium-free days in the NL-HELP group than in the usual care group. There were no statistically significant differences between the two groups in terms of delirium severity, length of hospital stay, delirium at 30 days after discharge, 30-day readmission, 30-day mortality, physical function or quality of life. CONCLUSIONS: This study demonstrated that NL-HELP could reduce the presence of delirium in delirious patients. No effect was observed in terms of shortening the length of hospital stay, reducing 30-day mortality, or improving quality of life. IMPACT: NL-HELP may be effective in reducing the presence of delirium in delirious patients. Further research is needed to determine whether the NL-HELP can improve patient outcomes (e.g. mortality and quality of life) in a larger study. PATIENT OR PUBLIC CONTRIBUTION: Caregivers of delirious patients were invited to provide intervention strategies to prevent or abate delirium, including environmental management, orientation communications and identification of alert signs. TRIAL REGISTRATION: This study was prospectively registered at the Chinese Clinical Trial Registry (https://www.chictr.org.cn/) Identifier: ChiCTR2300067874.

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The study investigated the effect of Compound Shougong Powder(CSGP) on the biological functions of triple-negative breast cancer(TNBC) cells and whether its mechanism of action was related to the epithelial-mesenchymal transition(EMT) signaling pathway. TNBC cells(MDA-MB-231 and BT-549) were treated with different concentrations of CSGP-containing serum. MTS assay was used to detect the effect of CSGP on the proliferation of TNBC cells. The EdU staining was used to detect the effect of CSGP on the proliferation of TNBC cells. Flow cytometry was used to examine the impact of CSGP on apoptosis of TNBC cells. Wound-healing and Transwell assays were used to evaluate the effects of different concentrations of CSGP on the migration and invasion capabilities of TNBC cells. RNA sequencing technology was utilized to elucidate its mechanism. Subsequently, qRT-PCR was performed to measure the mRNA expression levels of E-cadherin, N-cadherin, Slug, Snail, Vimentin, Twist, Zinc finger E-box-Binding homeobox 1(Zeb1), and Zinc finger E-box-Binding homeobox 2(Zeb2). Western blot was used to assess the protein expression levels of Slug, Vimentin, and E-cadherin. After intervention with CSGP, the proliferation of MDA-MB-231 and BT-549 cells significantly decreased, while the apoptosis rate markedly increased. The expression levels of the epithelial marker protein E-cadherin significantly increased, while the expression levels of the EMT-related transcription factors Slug and Vimentin showed a decrease. In conclusion, CSGP inhibits the EMT, thereby suppressing the malignant progression of TNBC.

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Samples of ambient volatile organic compounds （VOCs） were collected using SUMMA canisters at three Country Control Sites in Shijiazhuang during the spring of 2019, 2021, and 2022, which were detected using gas chromatography/mass spectrometry （GC/MS）. To investigate the characteristics and temporal variations of VOCs mass concentration levels, the online monitoring data of ozone （O3） and PM2.5 at the same site were also collected. Subsequently, the ozone formation potential （OFP） and secondary organic aerosol formation potential （SOAFP） were utilized to assess the chemical activity of VOCs. Additionally, the potential source areas of VOCs in spring in Shijiazhuang were further identified using the potential source contribution factor （PSCF） method and concentration weight trajectory analysis （CWT）. Hence, the major VOCs sources were evaluated with the VOCs initial mixing ratio. The results demonstrated that the averaged concentration of VOCs during the polluted period and clean period of spring in Shijiazhuang were 191.17 µg·m-3 and 122.18 µg·m-3, respectively. Meanwhile, the OFP was 361.23 µg·m-3 during the polluted period and 266.96 µg·m-3 during the clean period, whereas the SOAFP was 1.98 µg·m-3 and 1.61 µg·m-3, respectively. Therefore, effective control of benzene, toluene, ethylbenzene, and xylene （BTEX） is crucial for reducing PM2.5 and O3 pollution. Based on the results obtained from weight PSCF and CWT, the potential source areas of VOCs were further identified to be primarily located in the eastern Yuhua District, the high-tech district, and the northern Luancheng District of Shijiazhuang. These areas were influenced not only by local emissions but also by transport from neighboring regions, in which consistency between the CWT and PSCF results further supported these findings. Furthermore, the results obtained from the benzene/toluene/ethylbenzene （B/T/E） and xylene/benzene （X/B） ratios indicated that the main sources of VOCs in Shijiazhuang in spring were vehicle exhaust sources and burning sources, leading to a more serious air mass aging phenomenon. Hence, controlling vehicle emissions and implementing regional cooperative measures are the effective strategies for optimizing the air quality of Shijiazhuang.

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Circular RNAs (circRNAs) have emerged as essential regulators in cardiovascular disease, including acute myocardial infarction (AMI). This study investigated the role of circRNA Pum1_0014 in myocardial infarction (MI) and its underlying mechanisms using an H9C2 cell model. Through Sanger sequencing, nucleic acid electrophoresis, RNase R, and transcriptional inhibition experiments, Pum1_0014 was identified as a novel circRNA. The cell localization of circRNA Pum1_0014 was detected by qPCR and fluorescence in situ hybridization, and the results revealed that circRNA Pum1_0014 is predominantly located in the cytoplasm. StarBase (URL: http://starbase.sysu.edu.cn/) and TargetScan (URL: https://www.targetscan.org/vert_80/) were used to predict circRNA Pum1_0014 targeting miRNAs and miRNA targeting mRNA, and the results identified miR-146a-5p as a potential target of Pum1_0014, which in turn targets NF2. The plasmid encoding the mutant circRNA Pum1_0014 or the 3'UTR mutant NF2 was constructed, and the interaction between Pum1_0014 and miR-146a-5p or miR-146a-5p and NF2 was detected by luciferase reporter gene assay. The results confirmed the interactions between Pum1_0014, miR-146a-5p, and NF2. In the MI cell model, upregulation of circRNA Pum1_0014 and NF2 and downregulation of miR-146a-5p were observed. Knockdown of circRNA Pum1_0014 inhibited NF2 expression and activated the VEGF/PAK1 pathway, reducing cardiomyocyte apoptosis. Conversely, inhibition of miR-146a-5p and overexpression of NF2 had opposite effects. These findings suggest that circRNA Pum1_0014 acts through the miR-146a-5p/NF2 axis to reduce cardiomyocyte apoptosis in MI via the VEGF/PAK1/NF2 pathway.

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Chronic kidney disease (CKD) is a clinical syndrome characterized by persistent renal function decline. Renal fibrosis is the main pathological process in CKD, but an effective treatment does not exist. Stratifin (SFN) is a highly-conserved, multi-function soluble acidic protein. Therefore, this study explored the effects of SFN on renal fibrosis. First, we found that SFN was highly expressed in patients with CKD, as well as in renal fibrosis animal and cell models. Next, transforming growth factor-beta 1 (TGF-ß1) induced injury and fibrosis in human renal tubule epithelial cells, and SFN knockdown reversed these effects. Furthermore, SFN knockdown mitigated unilateral ureteral obstruction (UUO)-induced renal tubular dilatation and renal interstitial fibrosis in mice. Liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS), co-immunoprecipitation (Co-IP), and immunofluorescence co-localization assays demonstrated that SFN bound the non-muscle myosin-encoding gene, myosin heavy chain 9 (MYH9), in the cytoplasm of renal tubular epithelial cells. MYH9 knockdown also reduced Col-1 and α-SMA expression, which are fibrosis markers. Finally, silencing SFN decreased MYH9 expression, alleviating renal fibrosis. These results suggest that SFN promotes renal fibrosis in CKD by interacting with MYH9. This study may provide potential strategies for the treatment of CKD.

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This study explores the effects of Trib3 gene knockout on adult male rat spermatogenesis. Using CRISPR/Cas9, we knocked out the Trib3 gene in Wistar rats. Results indicate altered expression of PLZF, ID4, and c-KIT in knockout rats, suggesting impaired spermatogonial stem cell proliferation and differentiation. Histological analysis reveals reduced seminiferous tubule area and decreased spermatocyte numbers. Mating experiments demonstrate reduced offspring rates after the second self-mating in knockout rats. SYCP3, a meiosis marker, shows elevated expression in knockout rat testes at 14 days postpartum, suggesting an impact on reproductive processes. ELISA results indicate decreased testosterone, FSH, and FGF9 levels in knockout rat testicular tissues. In conclusion, Trib3 gene deletion may impede spermatogonial self-renewal and promote differentiation through the FSH-FGF9- c-KIT interaction and p38MAPK pathway, affecting reproductive capacity. These findings contribute to understanding the molecular mechanisms regulating spermatogenesis.

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Folsomia candida is a tiny soil-living arthropod belonging to the Collembola, which is an outgroup to Insecta. It resembles insects as having a pair of antennae and three pairs of thorax legs, while it also possesses three abdominal appendages: a ventral tube located in the first abdominal segment (A1), a retinaculum in A3, and a furca in A4. Collembolan Ubx and AbdA specify abdominal appendages, but they are unable to repress appendage marker gene Dll. The genetic basis of collembolan appendage formation and the mechanisms by which Ubx and AbdA regulate Dll transcription and appendage development remains unknown. In this study, we analysed the developmental transcriptomes of F. candida and identified candidate appendage formation genes, including Ubx (FcUbx). The expression data revealed the dominance of Dll over Ubx during the embryonic 3.5 and 4.5 days, suggesting that Ubx is deficient in suppressing Dll at early appendage formation stages. Furthermore, via electrophoretic mobility shift assays and dual luciferase assays, we found that the binding and repression capacity of FcUbx on Drosophila Dll resembles those of the longest isoform of Drosophila Ubx (DmUbx_Ib), while the regulatory mechanism of the C-terminus of FcUbx on Dll repression is similar to that of the crustacean Artemia franciscana Ubx (AfUbx), demonstrating that the function of collembolan Ubx is intermediate between that of Insecta and Crustacea. In summary, our study provides novel insights into collembolan appendage formation and sheds light on the functional evolution of Ubx. Additionally, we propose a model that collembolan Ubx regulates abdominal segments in a context-specific manner.

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AIM: To study the effect of the NLRP3/autophagy pathway on the photoreceptor inflammatory response and the protective mechanism of CY-09 and astaxanthin (AST). METHODS: ICR mice were intraperitoneally injected NaIO3, CY-09, AST successively and divided into 5 groups, including the control, NaIO3, NaIO3+CY-09, NaIO3+AST, and NaIO3+CY-09+AST groups. Spectral domain optical coherence tomography and flash electroretinogram were examined and the retina tissues were harvested for immunohistochemistry, enzyme linked immunosorbent assay (ELISA), and Western blotting. Retinal pigment epithelium cell line (ARPE-19 cells) and mouse photoreceptor cells line (661W cells) were also treated with NaIO3, CY-09, and AST successively. Cell proliferation was assessed by cell counting kit-8 (CCK-8) assay. Apoptosis was analyzed by flow cytometry. Changes in autophagosome morphology were observed by transmission electron microscopy. Quantitative polymerase chain reaction (qPCR) was used to detect NLRP3 and caspase-1. NLRP3, caspase-1, cleaved caspase-1, p62, Beclin-1, and LC3 protein levels were measured by Western blotting. IL-1ß and IL-18 were measured by ELISA. RESULTS: Compared with the control group, the activity of NaIO3-treated 661W cells decreased within 24 and 48h, apoptosis increased, NLRP3, caspase-1, IL-1ß and IL-18 levels increased, and autophagy-related protein levels increased (P<0.05). Compared with NaIO3 group, CY-09 and AST inhibited apoptosis (P<0.05), reduced NLRP3, caspase-1, IL-1ß and IL-18 expression (P<0.05), and inhibited autophagy. Compared with the other groups, CY-09 combined with AST significantly decreased NLRP3 expression and inhibited the expression of the autophagy-related proteins p62, Beclin-1, and LC3 in vitro and in vivo (P<0.05). CONCLUSION: CY-09 and AST inhibit NaIO3-induced inflammatory damage through the NLRP3/autophagy pathway in vitro and in vivo. CY-09 and AST may protect retina from inflammatory injury.

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Stress is an emotional state caused by an unexpected external environmental change or stimulus, and several experiments have demonstrated its negative impact on ovarian function, ultimately affecting reproductive ability. Melatonin (MT) has been shown to facilitate oocyte maturation and enhance ovarian function by regulating mitochondrial function. However, the specific effect and underlying molecular mechanisms of MT on stress-induced ovarian dysfunction remain largely unknown. In this study, we established a mouse model of chronic unpredictable mild stress (CUMS) to investigate its impact on ovarian function. Our findings revealed that CUMS led to premature ovarian insufficiency (POI) in mice, characterized by a reduction in follicle numbers and decreased levels of anti-Müllerian hormone (AMH) and bone morphogenetic protein 15 (BMP15). Furthermore, CUMS caused decreased expression of mitochondrial fission protein 1 (FIS1) and enhanced level of mitochondrial fusion protein optic atrophy 1(OPA1), mitofusin1(MFN1), as well as nucleus-encoded protein succinate dehydrogenase complex A (SDHA), reflecting mitochondrial dyshomeostasis. Additionally, CUMS resulted in excessive autophagy and apoptosis. However, MT reversed these effects and improved ovarian damage. Importantly, the protective effects of MT were mediated through the inhibition of the eIF2α-AFT4 pathway. Overall, this study provides valuable insights into the treatment of POI caused by CUMS.

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Background: Previous studies have shown that serotonin and its receptors are widely distributed in mammalian reproductive tisssues and play an important role in embryonic development. However, the specific effects of the serotonergic system on embryonic arrest (EA) and the underlying mechanism require further investigation. Methods: Chorionic villi were collected from patients with EA and healthy pregnant women. Western blotting (WB) and immunohistochemistry (IHC) were used to detect serotonin receptor 1B (HTR1B) levels and evaluate mitochondrial function. Additionally, HTR-8/SVneo cells were transfected with an HTR1B overexpression plasmid. Quantitative real-time polymerase chain reaction(qRT-PCR), Cell Counting Kit-8 (CCK-8), and wound healing assays were utilized to evaluate mitophagy level, cell proliferation and cell migration, respectively. Results: We discovered elevated HTR1B levels in the chorionic villi of the patients with EA compared to controls. Concurrently, we observed enhanced levels of nucleus-encoded proteins including mitofilin, succinate dehydrogenase complex subunit A (SDHA), and cytochrome c oxidase subunit 4 (COXIV), along with the mitochondrial fusion protein optic atrophy 1(OPA1), fission proteins mitochondrial fission protein 1(FIS1) and mitochondrial fission factor (MFF) in the EA group. Additionally, there was an excessive mitophagy levels in EA group. Furthermore, a notable activation of mitogen-activated protein kinase (MAPK) signaling pathway proteins including extracellular regulating kinase (ERK), c-Jun N-terminal kinase (JNK), and P38 was observed in the EA group. By overexpressing HTR1B in HTR-8/SVneo cells, we observed a significant reduction in cell proliferation and migration. HTR1B overexpression also caused an increase in levels of SDHA and FIS1, as well as an upregulation of mitophagy. Notably, the ERK inhibitor U0126 effectively mitigated these effects. Conclusion: These findings show that HTR1B influences mitochondrial homeostasis, promoting excessive mitophagy and impairing cell proliferation and migration by activating the MAPK signalling pathway during post-implantation EA. Therefore, HTR1B may serve as a potential therapeutic target for patients with EA.

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As a common inflammatory bowel disease, ulcerative colitis (UC) is featured with inflammation, oxidative damage, and the impairment of intestinal mucosal barrier, which bring threat to patients' quality of live. Hinesol, derived from Atractylodes lancea, is a unique sesquiterpenoid. Our study proposed to survey the effects and mechanism of hinesol in UC. UC mouse model was constructed using dextran sulfate sodium (DSS). Lipopolysaccharide (LPS) was applied for RAW264.7 cells stimulation to construct cell inflammatory model. The changes of disease activity index (DAI), body weight, colon length, and intestinal pathology in mice were analyzed to estimate the severity of colitis. Enzyme-linked immunosorbent assay was applied to check the changes of interleukin (IL)-1ß, IL-18, IL-6, and tumor necrosis factor (TNF)-α. The levels of myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-px), catalase (CAT), and malondialdehyde (MDA) were estimated by corresponding reagent kit. The changes of phosphorylated (p)-NF-κB P65, and p-IκBα, ZO-1, Occludin, Claudin-1, Src, XCL1, CCL2, and CXCL16 protein were examined using western blot. Flow cytometry and cell counting kit-8 assay were utilized for assessment of cell apoptosis and viability. We found that DSS reduced mice body weight, increased DAI, shorten colon length, and led to severe enteric mucosal injury, while hinesol improved the above symptoms induced by DSS. In DSS mice, hinesol raised the levels of ZO-1, Occludin, Claudin-1, SOD, GSH-px, and CAT and decreased the levels of TNF-α, IL-18, IL-1ß, IL-6, MPO, and MDA. Additionally, in DSS mice and LPS-stimulated RAW264.7 cells, hinesol inhibited the high expression of Src, XCL1, CCL2, CXCL16, p-NF-κB P65, and p-IκBα. The molecular docking showed that there was a good interaction between hinesol and Src. Moreover, in LPS-stimulated RAW 264.7 cells, Src overexpression partially reversed the inhibition of hinesol on cell apoptosis, pro-inflammatory factors, and oxidative stress. In conclusion, hinesol alleviated DSS-induced colitis, which might have a bearing on the inhibition of Src-mediated NF-κB and chemokine signaling pathway.

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INTRODUCTION: The Ribonucleoside-diphosphate Reductase subunit M2 (RRM2) is known to be overexpressed in various cancers, though its specific functional implications remain unclear. This aims to elucidate the role of RRM2 in the progression of Lung Adenocarcinoma (LUAD) by exploring its involvement and potential impact. METHODS: RRM2 data were sourced from multiple databases to assess its diagnostic and prognostic significance in LUAD. We evaluated the association between RRM2 expression and immune cell infiltration, analyzed its function, and explored the effects of modulating RRM2 expression on LUAD cell characteristics through laboratory experiments. RESULTS: RRM2 was significantly upregulated in LUAD tissues and cells compared to normal counterparts (p<0.05), with rare genetic alterations noted (approximately 2%). This overexpression clearly distinguished LUAD from normal tissue (area under the curve (AUC): 0.963, 95% confidence intervals (CI): 0.946-0.981). Elevated RRM2 expression was significantly associated with adverse clinicopathological characteristics and poor prognosis in LUAD patients. Furthermore, a positive association was observed between RRM2 expression and immune cell infiltration. Pathway analysis revealed a critical connection between RRM2 and the cell cycle signaling pathway within LUAD. Targeting RRM2 inhibition effectively suppressed LUAD cell proliferation, migration, and invasion while promoting apoptosis. This intervention also modified the expression of several crucial proteins, including the downregulation of CDC25A, CDC25C, RAD1, Bcl-2, and PPM1D and the upregulation of TP53 and Bax (p < 0.05). CONCLUSION: Our findings highlight the potential utility of RRM2 expression as a biomarker for diagnosing and predicting prognosis in LUAD, shedding new light on the role of RRM2 in this malignancy.

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Transcriptional reprogramming is critical for plant immunity. Several calmodulin (CaM)-binding protein 60 (CBP60) family transcription factors (TFs) in Arabidopsis (Arabidopsis thaliana), including CBP60g, Systemic Acquired Resistance Deficient 1 (SARD1), CBP60a, and CBP60b, are critical for and show distinct roles in immunity. However, there are additional CBP60 members whose function is unclear. We report here that Arabidopsis CBP60c-f, four uncharacterized CBP60 members, play redundant roles with CBP60b in the transcriptional regulation of immunity responses, whose pCBP60b-driven expression compensates the loss of CBP60b. By contrast, neither CBP60g nor SARD1 is inter-changeable with CBP60b, suggesting clade-specific functionalization. We further show that function of CBP60b clade TFs relies on DNA-binding domains (DBDs) and CaM-binding domains, suggesting that they are downstream components of calcium signaling. Importantly, we demonstrate that CBP60s encoded in earliest land plant lineage Physcomitrium patens and Selaginella moellendorffii, are functionally homologous to Arabidopsis CBP60b, suggesting that the CBP60b clade contains the prototype TFs of the CBP60 family. Furthermore, tomato and cucumber CBP60b-like genes rescue the defects of Arabidopsis cbp60b and activate the expression of tomato and cucumber SALICYLIC ACID INDUCTION DEFICIIENT2 (SID2) and ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) genes, suggesting that immune response pathways centered on CBP60b are also evolutionarily conserved. Together, these findings suggest CBP60b clade transcription factors are functionally conserved in evolution and positively mediate immunity.

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INTRODUCTION: Maternal smoking during pregnancy disturbs fetal lung development, and induces in their offspring childhood respiratory diseases. Whether it has a continued impact on offspring adult lung health and exerts a casual effect of chronic respiratory diseases (CRDs), remains uncertain. We seek to determine the causal relationships between maternal smoking around birth and offspring adult CRDs, using summary data from previously described cohorts. METHODS: Mendelian randomization (MR) study was used to analyze the genome-wide associations of maternal smoking around birth and offspring adult CRDs, including respiratory insufficiency, chronic obstructive pulmonary disease (COPD), related respiratory insufficiency, emphysema, COPD, COPD hospital admissions, early onset of COPD, later onset of COPD, asthma, idiopathic pulmonary fibrosis (IPF), lung cancer (LC), small cell lung carcinoma (SCLC), and lung squamous cell carcinoma (LUSC). RESULTS: After removing single-nucleotide polymorphisms (SNPs) associated with smoking by the offspring, maternal smoking around birth was associated with increased risk of offspring adult respiratory diseases (OR=1.14; 95% CI: 1.013-1.284; p=0.030), respiratory insufficiency (OR=2.413; 95% CI: 1.039-5.603; p=0.040), COPD (OR=1.14; 95% CI: 1.013-1.284; p=0.003), and asthma (OR=1.336; 95% CI: 1.161-1.538; p<0.001). Besides, maternal smoking during pregnancy was associated with a greater risk of LUSC (OR=1.229; 95% CI: 0.992-1.523; p=0.059) than the risk of IPF (OR=1.001; 95% CI: 0.999-1.003; p=0.224), LC (OR=1.203; 95% CI: 0.964-1.501; p=0.103), or SCLC (OR=1.11; 95% CI: 0.77-1.601; p=0.577). CONCLUSIONS: In this MR analysis, maternal smoking around birth caused a strong risk factor for the offspring to develop lung problems and CRDs in adulthood. The policy related to smoking cessation for mothers during pregnancy should be encouraged.