Shuangdan Jiedu Decoction improved LPS-induced acute lung injury by regulating both cGAS-STING pathway and inflammasome.

ETHNOPHARMACOLOGICAL RELEVANCE: Shuangdan Jiedu Decoction (SJD) is a formula composed of six Chinese herbs with heat-removing and detoxifying, antibacterial, and anti-inflammatory effects, which is clinically used in the therapy of various inflammatory diseases of the lungs including COVID-19, but the therapeutic material basis of its action as well as its molecular mechanism are still unclear. AIM OF THE STUDY: The study attempted to determine the therapeutic effect of SJD on LPS-induced acute lung injury (ALI), as well as to investigate its mechanism of action and assess its therapeutic potential for the cure of inflammation-related diseases in the clinical setting. MATERIALS AND METHODS: We established an ALI model by tracheal drip LPS, and after the administration of SJD, we collected the bronchoalveolar lavage fluid (BALF) and lung tissues of mice and examined the expression of inflammatory factors in them. In addition, we evaluated the effects of SJD on the cyclic guanosine monophosphate-adenosine monophosphate synthase -stimulator of interferon genes (cGAS-STING) and inflammasome by immunoblotting and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: We demonstrated that SJD was effective in alleviating LPS-induced ALI by suppressing the levels of pro-inflammatory cytokines in the BALF, improving the level of lung histopathology and the number of neutrophils, as well as decreasing the inflammatory factor-associated gene expression. Importantly, we found that SJD could inhibit multiple stimulus-driven activation of cGAS-STING and inflammasome. Further studies showed that the Chinese herbal medicines in SJD had no influence on the cGAS-STING pathway and inflammasome alone at the formulated dose. By increasing the concentration of these herbs, we observed inhibitory effects on the cGAS-STING pathway and inflammasome, and the effect exerted was maximal when the six herbs were combined, indicating that the synergistic effects among these herbs plays a crucial role in the anti-inflammatory effects of SJD. CONCLUSIONS: Our research demonstrated that SJD has a favorable protective effect against ALI, and its mechanism of effect may be associated with the synergistic effect exerted between six Chinese medicines to inhibit the cGAS-STING and inflammasome abnormal activation. These results are favorable for the wide application of SJD in the clinic as well as for the development of drugs for ALI from herbal formulas.

Effects of salinity and betaine addition on anaerobic granular sludge properties and microbial community succession patterns in organic saline wastewater.

In this study, the effects of different salinity gradients and addition of compatible solutes on anaerobic treated effluent water qualities, sludge characteristics and microbial communities were investigated. The increase in salinity resulted in a decrease in particle size of the granular sludge, which was concentrated in the range of 0.5-1.0 mm. The content of EPS (extracellular polymeric substances) in the granular sludge gradually increased with increasing salinity and the addition of betaine (a typical compatible solute). Meanwhile, the microbial community structure was significantly affected by salinity, with high salinity reducing the diversity of bacteria. At higher salinity, Patescibacteria and Proteobacteria gradually became the dominant phylum, with relative abundance increasing to 13.53% and 12.16% at 20 g/L salinity. Desulfobacterota and its subordinate Desulfovibrio, which secrete EPS in large quantities, dominated significantly after betaine addition.Their relative abundance reached 13.65% and 7.86% at phylum level and genus level. The effect of these changes on the treated effluent was shown as the average chemical oxygen demand (COD) removal rate decreased from 82.10% to 79.71%, 78.01%, 68.51% and 64.55% when the salinity gradually increased from 2 g/L to 6, 10, 16 and 20 g/L. At the salinity of 20 g/L, average COD removal increased to 71.65% by the addition of 2 mmol/L betaine. The gradient elevated salinity and the exogenous addition of betaine played an important role in achieving stability of the anaerobic system in a highly saline environment, which provided a feasible strategy for anaerobic treatment of organic saline wastewater.

Integrating carbon quantum dots with oxygen vacancy modified nickel-based metal organic frameworks for photocatalytic CO2 reduction to CH4 with approximately 100 % selectivity.

Solar-light-driven reduction of CO2 into renewable fuels has great potential in the production of sustainable energy, addressing the energy crisis and environmental problems simultaneously. However, it is a significant challenge to achieve high selectivity for the conversion of CO2 into CH4, which is a type of fuel with a high calorific value. Herein, carbon quantum dots (CQDs) were integrated with an oxygen vacancy modified nickel-based metal organic frameworks (NiMOFs) to form the CQDs-X/NiMOFV series, which exhibited superior performance for CO2 photoreduction into CH4 compared with pure NiMOFs in the presence of hole scavengers under visible light irradiation. The highest yielding rate of CH4 (1 mmol g-1 h-1) and selectivity (97.58 %) were obtained using a CQDs-25/NiMOFV catalyst. Most importantly, in diluted CO2 atmosphere, the yield of CH4 was almost unchanged and the selectivity of CH4 over CQDs-25/NiMOFV was higher than that in pure CO2. The superior performance of CQDs-25/NiMOFV may be attributed to the following two factors: (i) both CQDs and oxygen vacancies facilitate the transmission of electrons to promote the eight-electron reaction producing CH4, and (ii) oxygen vacancies can act as the electron trap to capture the photogenerated electrons to react with adsorbed CO2 on Ni2+. This study offers a valuable strategy for designing efficient photocatalysts to convert CO2 into CH4 with superior selectivity.

Expression and Significance of the Circular RNA circ_0001438 in the Development of Gastric Cancer.

Gastric cancer has become a great challenge to human health in the world. We studied the expression and role of the circular RNA 0001438 (circ_0001438) with the aim of finding a biomarker to assess the prognosis of gastric cancer. Through a polymerase chain reaction, circ_0001438 expression in gastric cancer was detected. Chi-square test, multi-factor Cox regression, and Kaplan-Meier analyses were used to determine the association between circ_0001438 and the patients' clinical condition and prognosis. Using the luciferase reporter gene system, the interaction between circ_0001438 and miR-1290 was analyzed, and the regulatory impact of circ_0001438/miR-1290 on the activity of gastric cancer cells was examined flowing the Transwell assay and CCK8 assay. In gastric cancer tissues and cells, circ_0001438 expression was downregulated, and miR-1290 expression was upregulated and the two were negatively correlated. miR-1290 inhibitors were transfected and significantly increased the activity of circ_0001438 luciferase, while miR-1290 mimics decreased the activity. Overexpression of circ_0001438 decreased miR-1290 expression and inhibited the proliferation and metastasis of gastric cancer cells, which was reversed when miR-1290 mimics were transfected. Additionally, there was a correlation between circ_0001438 expression and lymph node metastases, tumor size, and TNM stage of gastric cancer. Low circ_0001438 expression predicts poor prognosis of gastric cancer patients. circ_0001438 is a biomarker for tumor development and clinical prognosis in gastric cancer. It works by downregulating miR-1290 to control the activity of gastric cancer cells.

Remimazolam attenuates lipopolysaccharide-induced neuroinflammation and cognitive dysfunction.

OBJECTIVE: Remimazolam, a novel benzodiazepine, is widely used as an anesthetic in endoscopic procedures; however, its effects on cognitive function remain unclear, limiting its broader application in general anaesthesia. Neuroinflammation is a well-established key factor in the etiology and progression of cognitive dysfunction, including conditions such as Alzheimer's disease, Parkinson's disease, postoperative delirium, and postoperative cognitive dysfunction. Preclinical studies have demonstrated that remimazolam exerts anti-inflammatory and neuroprotective effects, and clinical reports indicate a reduced incidence of postoperative delirium in patients treated with remimazolam. Nevertheless, whether remimazolam improves cognitive function through its anti-inflammatory properties remains uncertain. This study aimed to investigate the neuroprotective effects of remimazolam and its underlying mechanism in a lipopolysaccharide (LPS)-induced model of neuroinflammation, neuronal injury, and cognitive dysfunction METHODS: C57BL/6 J male mice were administered LPS intraperitoneally to establish a model of neuroinflammation-induced cognitive impairment. A subset of mice received remimazolam via intraperitoneal injection 30 minutes prior to LPS administration. Cognitive performance was evaluated using behavioural tests, including the Morris Water Maze (MWM), Novel Object Recognition (NOR) test, and Open Field Test (OFT). Hippocampal tissues were analyzed by haematoxylin-eosin (HE) staining to assess structural changes. Inflammatory markers, including Interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α, were quantified using enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR. Immunofluorescence was used to detect translocator protein (TSPO) and markers of microglia activation (IBA-1, CD16/32, and CD206). RESULTS: (1) Remimazolam reversed LPS-induced cognitive deficits, as evidenced by shorter spatial exploration latency and increased platform crossings in the MWM, and an elevated recognition index in the NOR test. (2) Remimazolam improved hippocampal morphology, reducing LPS-induced neuronal damage. (3) Remimazolam significantly decreased levels of hippocampal inflammatory cytokines, inhibited microglial activation, promoted M2-type microglia polarization, and increased TSPO expression. CONCLUSION: Remimazolam demonstrated neuroprotective and anti-neuroinflammatory effects in a mouse model of LPS-induced cognitive impairment. These effects are likely mediated through the regulation of TSPO, which inhibits microglial activation and promotes the polarization of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype.

Controlling lamination and directional growth of ß-sheets via hydrophobic interactions: The strategies and insights.

The self-assembling morphologies of proteins, nucleic acids, and peptides are well correlated with their functioning in biological systems. In spite of extensive studies for the morphologies regulating, the directional control of the assembly morphology structure for the peptides still remains challenging. Here, the directional structure control of a bola-like peptide Ac-KIIF-CONH2 (KIIF) was realized by introducing different amount of acetonitrile to the system. The morphologies were characterized by transmission electron microscopy (TEM) and atomic force microscopy (AFM), and the secondary structure was evaluated by circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR). The results demonstrated that the introducing of different amount of acetonitrile has significantly tuned the hydrophobic interactions amongst the side chains, thus affecting the self-assembling morphologies. As acetonitrile content increased, the assemblies changed from nanotubes to helical/twisted ribbons and then to thin fibrils, with a steady decrease in the width. In contrast, the assemblies changed from thin fibrils to helical/twisted ribbons, and then to matured nanotubes, exhibiting a steady increase in the width with peptide concentration increasing. Complementary molecular dynamics (MD) simulations demonstrated the important role of acetonitrile in controlling the hydrophobic interactions, providing microscopic evidence for the structure transition process. We believe such observations provide important insights into the design and fabrication of functional materials with controlled shape and size.

Silk protein: A novel antifungal and edible coating for strawberry preservation.

In this study, an antimicrobial component, silk protease inhibitors (SPIs), was extracted from discarded silkworm cocoons, and a suitable degumming method for obtaining regenerated silk fibroin (SF) was screened. An edible antimicrobial coating was prepared by mixing SPIs with SF for evaluation of potential in strawberries preservation. Results demonstrated that SPI could effectively inhibit mycelial growth and spore germination. The alkaline protease method exhibited the highest degumming rate of 24.4 %. The SPI-SF coating exhibited excellent mechanical properties, high water vapor permeability, and easy washability. Within 10 days, seedlings treatment with SPI-SF coating solution showed a germination rate of 94.3 %, and exhibited good biocompatibility with HepG2 cells. Coating with SPI-SF led to increase in the storage period of strawberries to 10-14 days, concurrent with considerable reduction in decay rate at room temperature. Conclusively, this study demonstrates the potential of SPI-SF edible coating in strawberries preservation.

Estimation of gaseous polycyclic aromatic hydrocarbons (PAHs) and characteristics of atmospheric PAHs at a traffic site in Kanazawa, Japan.

Size-fractionated particulate matter (PM2.5 and PM>2.5) was collected at a traffic site in Kanazawa, Japan in a seasonal sampling work in 2020. Nine polycyclic aromatic hydrocarbons (4- to 6-ring PAHs) were determined in fine and coarse particles. The gas/particle partitioning coefficients (Kp) of the PAHs were calculated from the supercooled liquid vapour pressure and octanol-air partitioning coefficient based on the relationships obtained in previous traffic pollution-related studies. Gaseous PAHs were estimated by Kp and the concentrations of PM and particulate PAHs. The concentrations of total PAHs were 32.5, 320.1 and 5646.2 pg/m3 in the PM>2.5, PM2.5 and gas phases, respectively. Significant seasonal trends in PAHs were observed (particle phase: lowest in summer, gas phase: lowest in spring, particle and gas phase: lowest in spring). Compared to 2019, the total PAH concentrations (in particles) decreased in 2020, especially in spring and summer, which might be due to reduced traffic trips during the COVID-19 outbreak. The incremental lifetime cancer risk (ILCR) calculated from the toxic equivalent concentrations relative to benzo[a]pyrene (BaPeq) was lower than the acceptable limit issued by the US Environmental Protection Agency, indicating a low cancer risk in long-term exposure to current PAH levels. It is notable that gaseous PAHs considerably contributed to BaPeq and ILCR (over 50%), which highlighted the significance of gaseous PAH monitoring for public health protection. This low-cost estimation method for gaseous PAHs can be expected to reliably and conveniently obtain PAH concentrations as a surrogate for traditional sampling in the future work.

A rare prenylated isoflavone-quinone from the roots of Flemingia philippinensis.

In order to make more rational use of Flemingia Philippinensis, a systematic separation from the roots of F. philippinensis was performed in the current study. The investigation of chemical constituents resulted in the isolation of a rare prenylated isoflavone-quinone, fleminquinone A (1), together with four known analogues (2-5). Their structures were established by extensive physical and spectroscopic data analysis. Anti-inflammatory activities of the isolated compounds were evaluated in lipopolysaccharide induced mouse mononuclear macrophage leukemia cells RAW 264.7 model. Compound 1 exhibited significant inhibitory effects on LPS-induced NO production and COX-2. Compound 1 also significantly affected the levels of inflammatory cytokines.

Deciphering the oncogenic potential of ADAM9 in hepatocellular carcinoma through bioinformatics and experimental approaches.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. This study investigates the role and mechanisms of ADAM9 as a biomarker and potential therapeutic target in HCC. Utilizing RNA-sequencing data and clinicopathological characteristics from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we conducted survival and meta-analyses, functional enrichment, and immune infiltration studies. Additionally, we evaluated the effects of ADAM9 silencing on HCC cell proliferation, migration, and invasion through in vitro experiments. Our results demonstrate that high ADAM9 expression is associated with poor prognosis and increased immune infiltration in HCC patients. Furthermore, ADAM9 knockdown significantly inhibited tumor cell proliferation and migration. These findings indicate that ADAM9 is a promising prognostic biomarker and potential therapeutic target in HCC. In conclusion, ADAM9 could offer avenues for developing strategies to inhibit tumor progression and improve patient outcomes.

Association between blood heavy metals and diabetic kidney disease among type 2 diabetic patients: a cross-sectional study.

Studies on the correlation of exposure to metals with diabetic kidney disease (DKD) is scarce, especially concerning the impact of mixed metals on DKD. This study aimed to explore the association of blood heavy metals with DKD risk among type 2 diabetes mellitus (T2DM) patients. This cross-sectional study enrolled patients with T2DM in NHANES 2011-2020. ICP‒MS was applied to detect five metals, namely, Pb, Cd, Hg, Se and Mn, in blood. At the same time, the impacts of exposure to single and mixed metals on DKD were assessed using multivariable logistic regression, WQS, and BKMR models. The relationship was examined based on age, sex, BMI, hypertension, smoking status and PIR. Totally 2362 participants were enrolled for final analysis. Among them, 634 (26.84%) patients undergoing T2DM had DKD. Logistic regression indicated that, Pb (Q4: OR [95% CI]: 1.557 [1.175, 2.064]) was related to DKD when all covariates were adjusted. The WQS analysis, which was set in a positive directional mode, suggested that Pb was correlated positively with a higher incidence of DKD. In BKMR analysis, linear dose‒response curves were generated for Pb when fixing the other metals in the 50th percentile. In addition, exposure to mixed metals was significantly positively related to DKD. Subgroup analysis during logistic regression demonstrated that Pb was significantly and positively related to DKD in females, over 50 years, those with over 25 kg/m2, no hypertension, no smoking status and under PIR. Serum albumin (ALB) did not regulate the indirect impact of blood Pb on DKD risk. The results showed that the increased mixed metal concentration may lead to an increased DKD risk among patients with T2DM. Blood Pb is positively related to the DKD risk in diabetic patients, especially, in females, over 50 years, those with over 25 kg/m2, no hypertension, no smoking status and under PIR in T2DM patients. According to our observations, Pb absorption at least slightly influences DKD occurrence and progression. More studies are needed to validate the results in this work and illustrate the relevant biological mechanism.

The clinical outcomes of induction chemotherapy followed by radiotherapy vs. chemoradiotherapy in locally advanced hypopharyngeal squamous cell carcinoma: A retrospective study.

Background: Stage III and IVA-B hypopharyngeal carcinoma presents a substantial risk of recurrence and metastasis. The treatment strategy remains uncertain. The objective of this observational study was to compare the outcomes of induction chemotherapy followed by radiotherapy (ICRT) and induction chemotherapy followed by chemoradiotherapy (ICCRT) in the treatment of locally advanced hypopharyngeal squamous cell carcinoma. Methods: 58 patients with stage III and IVA-B hypopharyngeal squamous cell carcinoma treated with ICRT (n = 26) or ICCRT (n = 32) were enrolled in the study. Baseline variables and toxicity rates were compared by Chi-squared test. Survival curves were constructed by the Kaplan-Meier method and compared by log-rank test. Multivariate Cox proportional hazard analysis was performed to evaluate the potential survival effects. Results: There were no significant differences in gender, age, smoking, drinking, T category, N category, overall stage, induction chemotherapy schemes and cycles between the two groups. The median follow-up time was 36.3 months (range, 2.3-97.5 months). The 2-year recurrence-free survival (RFS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and the 1-year, 2-year overall survival (OS) expressed no significant differences between the two groups. Furthermore, induction chemotherapy regimen of TPF achieved better OS than TP or PF (hazard ratio [HR] 0.395, 95 % confidence interval [CI] 0.178-0.879; P = 0.023), OS of patients in N2-3 category was worse than N0-1 (HR 2.594, 95 % CI 1.230-5.471; P = 0.012). In addition, the grade 3-4 therapy-associated toxicities during radiotherapy were higher in the chemoradiotherapy group than in radiotherapy alone group (P = 0.020). Conclusion: Following induction chemotherapy in patients with stage III/IVA-B hypopharyngeal squamous cell carcinoma, the concurrent chemoradiotherapy regimen provided similar survival rates with radiotherapy alone. Meanwhile, the incidence of treatment-related side effects during radiotherapy after induction chemotherapy were lower than that during chemoradiotherapy.

Impact of chronic stress on intestinal mucosal immunity in colorectal cancer progression.

Chronic stress is a significant risk factor that contributes to the progression of colorectal cancer (CRC) and has garnered considerable attention in recent research. It influences the distribution and function of immune cells within the intestinal mucosa through the "brain-gut" axis, altering cytokine and chemokine secretion and creating an immunosuppressive tumor microenvironment. The intestine, often called the "second brain," is particularly susceptible to the effects of chronic stress. Cytokines and chemokines in intestinal mucosal immunity（IMI） are closely linked to CRC cells' proliferation, metastasis, and drug resistance under chronic stress. Recently, antidepressants have emerged as potential therapeutic agents for CRC, possibly by modulating IMI to restore homeostasis and exert anti-tumor effects. This article reviews the role of chronic stress in promoting CRC progression via its impact on intestinal mucosal immunity, explores potential targets within the intestinal mucosa under chronic stress, and proposes new approaches for CRC treatment.

Clonal hematopoiesis of indeterminate potential: the root cause of, and fertile ground for, hematological malignancies.

Clonal hematopoiesis (CH) of indeterminate potential (CHIP), characterized by propagation of blood cell clones carrying somatic mutations in specific driver genes, is increasingly recognized as a critical factor in the development of hematological malignancies. This phenomenon, which often emerges with age, underscores the complex interplay between genetic predisposition and environmental influences in cancer initiation and progression. Recent years have witnessed significant advances in our understanding of the link between CHIP and hematological diseases. In this review, we provide a comprehensive overview of the features of CHIP and explore its role in promoting tumorigenesis and influencing treatment outcomes for blood cancers. Finally, we summarize current available tools for risk stratification and discuss management strategies for patients with CHIP.

High complex anal fistula managed by the modified transanal opening of the intersphincteric space via the inter-sphincteric approach: A case report.

BACKGROUND: High complex anal fistulas are epithelialized tunnels, with the main fistula piercing above the deep external sphincter and the internal opening approaching the dentate line. Conventional surgical procedures for high complex anal fistulas remove most of the external sphincter and damage the anorectal ring. Postoperative loss of anal function can cause physical and mental damage. Transanal opening of the intersphincteric space (TROPIS) is an effective procedure that completely preserves the external anal sphincter. However, its clinical application is limited by challenges in the localization of the internal opening of a fistula and the high risk of complications. On the basis of our clinical experience, we modified the TROPIS procedure for the treatment of treating high complex anal fistulas. CASE SUMMARY: A patient with a high complex anal fistula located above the anorectal ring underwent modified TROPIS, which involved sepsis drainage and identification of the internal opening in the intersphincteric space. The patient with the high complex anal fistula recovered well postoperatively, without any postoperative complications or anal dysfunction. Anal function returned to normal after 17 months of follow-up. CONCLUSION: The modified TROPIS procedure is the most minimally invasive surgery for anal fistulas that minimally impairs anal function. It allows the complete removal of infected anal glands and reduces the risk of postoperative complications. Modified TROPIS via the intersphincteric approach is an alternative sphincter-preserving treatment for high complex anal fistulas.

Predictive Value of White Matter Hyperintensities for Early Neurological Deterioration in Patients with Embolic Stroke of Undetermined Source.

Objective: To explore the role of white matter hyperintensities (WMH) in predicting early neurological deterioration (END) in patients with embolic stroke of undetermined source (ESUS) without reperfusion therapy. Methods: In a retrospective analysis, 111 acute ESUS patients not treated with reperfusion therapy were enrolled. WMH severity was evaluated using the Fazekas scale, with patients categorized into mild (Fazekas score ≤ 2) or moderate-to-severe (Fazekas score ≥ 3) WMH groups. Clinical data were compared between the groups, and END was monitored within 72 hours of hospital admission. The association between WMH and END was assessed using binary logistic regression. Results: Patients with moderate-to-severe WMH were significantly older (p = 0.001) and more likely to have a history of stroke (28.6% vs 10.5%, p = 0.017) compared to the mild WMH group. The END group (n=16) presented with higher baseline NIHSS scores and a greater prevalence of moderate-to-severe WMH (p < 0.05). Binary logistic regression identified moderate-to-severe WMH (OR = 4.012, 95% CI: 1.080-14.906, p = 0.038), smoking (OR = 4.368, 95% CI: 1.171-16.293, p = 0.028), and diabetes mellitus (OR = 3.986, 95% CI: 1.007-15.789, p = 0.049) as independent predictors of END in ESUS patients. Conclusion: Moderate-to-severe WMH is an independent risk factor for END in ESUS patients not receiving reperfusion therapy, highlighting the importance of considering WMH in the clinical evaluation and management of stroke patients.

NPF and sNPF can regulate the feeding behaviour and affect the growth and antioxidant levels of the rice brown planthopper, Nilaparvata lugens.

Neuropeptide F (NPF) and short neuropeptide F (sNPF) are important neuropeptides and mainly affect feeding behaviour of insects. However, the regulation of insect feeding behaviour by NPF and sNPF appears to differ between species, and it is not clear how NPF and sNPF regulate the food intake of the brown planthopper (Nilaparvata lugens). Therefore, the functions of NPF and sNPF in regulating food intake and affecting the growth and antioxidant levels of N. lugens fed on host rice plants were investigated by knocking down NPF and sNPF respectively and simultaneously knocking down both of them by RNA interference. The results showed that NPF and sNPF were mainly expressed in the head of N. lugens, and N. lugens increased food intake after NPF and sNPF were knocked down, which was reflected in the prolonged duration of N4a and N4b waves in the electrical penetration graph (EPG) experiment after knocking down NPF and sNPF. In addition, knocking down NPF and sNPF led to the increase of body weight and mortality of N. lugens, and also led to the increase of antioxidant level of N. lugens. So it was concluded that NPF and sNPF could regulate food intake, maintain body weight stability and oxidative balance in N. lugens. Our study clarified the molecular mechanism of NPF and sNPF regulating feeding behaviour and affect the growth and antioxidant level of N. lugens.

Efficacy and safety of surufatinib in the treatment of patients with neuroendocrine tumor: a real-world study in Chinese population.

BACKGROUND: Neuroendocrine tumors (NETs) are rare neoplasms that originate from peptidergic neurons and neuroendocrine cells. Due to their increasing incidence, effective treatment strategies are required. Surufatinib, a novel small-molecule inhibitor with antiangiogenic and immunomodulatory effects, has shown promise in clinical trials for advanced NETs. However, the efficacy and safety of surufatinib are influenced by multiple factors, and there is currently a lack of sufficient real-world studies to explore these potential influencing factors. METHODS: We conducted a retrospective study on 133 patients with NETs who were treated with surufatinib at Sun Yat-sen University Cancer Center. Patients were histologically confirmed to have primary NETs. Statistical analyses, including Cox regression models and Kaplan-Meier curves, were conducted to assess the impact of the primary tumor site on progression-free survival (PFS) and overall survival (OS). RESULTS: Patients with gastroenteropancreatic NETs (GEP-NETs) exhibited significantly longer PFS and OS compared to extraGEP-NETs patients. Subgroup analyses also revealed variations in survival outcomes among patients with liver metastases depending on the primary tumor site. Adverse events (AEs), including proteinuria and increased bilirubin, were more common in GEP-NETs patients. These findings emphasize the importance of considering primary tumor site in treatment decisions for NETs. CONCLUSIONS: Primary tumor site is a critical factor influencing the efficacy of surufatinib in NETs. Clinicians should consider this factor when determining treatment strategies.

Alternative splicing in the genome of HPV and its regulation.

Persistent infection with high-risk human papillomavirus (HR-HPV) is the main cause of cervical cancer. These chronic infections are characterized by high expression of the HPV E6 and E7 oncogenes and the absence of the L1 and L2 capsid proteins. The regulation of HPV gene expression plays a crucial role in both the viral life cycle and rare oncogenic events. Alternative splicing of HPV mRNA is a key mechanism in post-transcriptional regulation. Through alternative splicing, HPV mRNA is diversified into various splice isoforms with distinct coding potentials, encoding multiple proteins and influencing the expression of HPV genes. The spliced mRNAs derived from a donor splicing site within the E6 ORF and one of the different acceptor sites located in the early mRNA contain E6 truncated mRNAs, named E6*. E6* is one of the extensively studied splicing isoforms. However, the role of E6* proteins in cancer progression remains controversial. Here, we reviewed and compared the alternative splicing events occurring in the genomes of HR-HPV and LR-HPV. Recently, new HPV alternative splicing regulatory proteins have been continuously discovered, and we have updated the regulation of HPV alternative splicing. In addition, we summarized the functions of known splice isoforms from three aspects: anti-tumorigenic, tumorigenic, and other cancer-related functions, including not only E6*, but also E6^E7, E8^E2, and so on. Comprehending their contributions to cancer development enhances insights into the carcinogenic mechanisms of HPV and explores the potential utility of alternative splicing in the diagnosis and treatment of cervical cancer.