Ferroptosis-related LINC02535/has-miR-30c-5p/EIF2S1 axis as a novel prognostic biomarker involved in immune infiltration and progression of PDAC.

BACKGROUND: PDAC, also known as pancreatic ductal adenocarcinoma, is often diagnosed at a late stage due to nonspecific symptoms and a distinct lack of reliable biomarkers for timely diagnosis. Ferroptosis, a novel non-apoptotic cell death mode discovered in recent years, is strongly linked to the progression of PDAC and the evasion of the immune system. The objective of this study is to discover a novel ceRNA biomarker associated with ferroptosis and investigate its possible molecular mechanisms and therapeutic potential in PDAC. METHODS: Based on the FerrDb and TCGA databases, the R survival package was used to screen for ferroptosis-related mRNAs associated with PDAC prognosis. The ferroptosis-related ceRNA network was identified by miRTarBase, miRNet, and starBase and visualized using Cytoscape. The LASSO regression analysis was used to build a risk model associated with ceRNA. Additionally, we investigated the correlation between the ceRNA axis and the infiltration of immune cells in PDAC by employing the ssGSEA algorithm. Spearman correlation analysis was used to investigate the association between the ceRNA network and the expression levels of immune checkpoint genes in PDAC. The prediction of potential medications for PAAD patients with high risk scores was conducted using the R package oncoPredict and the Genomics of Drug Sensitivity in Cancer (GDSC) repository. Expression levels of LINC02535 in clinical specimens and PDAC cell lines were determined using qRT-PCR. CCK-8, colony formation, EdU, wound healing, and transwell assays were performed to assess the impact of reducing LINC02535 on the growth, migration, and invasion of PDAC cell lines BxPC3 and PANC1. RESULTS: We first discovered a new LINC02535/miR-30c-5p/EIF2S1 axis associated with ferroptosis and created a prognostic nomogram for predicting overall survival. Meanwhile, the risk scores of the LINC02535/miR-30c-5p/EIF2S1 axis associated with ferroptosis were linked to immune subtypes in PDAC. The high immune infiltration subtype exhibited elevated ceRNA risk scores and EIF2S1 expression. The correlation analysis revealed a positive correlation between ceRNA risk scores and four immune cells, namely Activated CD4 T cell, Memory B cell, Neutrophil, and Type 2 T helper cell, as well as four immune checkpoint genes, namely CD274, HAVCR2, PDCD1LG2, and TIGIT. The analysis of drug sensitivity indicated that individuals with a high-risk score may exhibit greater sensitivity to inhibitors targeting MEK1/2 compared to those with a low-risk score. In our validation experiments, it was observed that the expression of LINC02535 was increased in both PDAC tissues and cell lines. Additionally, the inhibition of LINC02535 resulted in decreased proliferation, migration, and invasion of PDAC cells. Rescue experiments demonstrated that LINC02535 promoted PDAC cell growth and metastasis by upregulating EIF2S1 expression. CONCLUSION: To summarize, a novel ferroptosis-associated LINC02535/miR-30c-5p/EIF2S1 ceRNA network for PDAC patients was established. The analysis of this network's functionality offers potential insights for clinical decision-making and the advancement of precision medicine.

Commiphora myrrha n-hexane extract suppressed breast cancer progression through induction of G0/G1 phase arrest and apoptotic cell death by inhibiting the Cyclin D1/CDK4-Rb signaling pathway.

Background: Breast cancer (BC) is one of the most frequently observed malignancies globally, yet drug development for BC has been encountering escalating challenges. Commiphora myrrha is derived from the dried resin of C. myrrha (T. Nees) Engl., and is widely adopted in China for treating BC. However, the anti-BC effect and underlying mechanism of C. myrrha remain largely unclear. Methods: MTT assay, EdU assay, and colony formation were used to determine the effect of C. myrrha n-hexane extract (CMHE) on the proliferation of human BC cells. Cell cycle distribution and apoptosis were assessed via flow cytometry analysis. Moreover, metastatic potential was evaluated using wound-scratch assay and matrigel invasion assay. The 4T1 breast cancer-bearing mouse model was established to evaluate the anti-BC efficacy of CMHE in vivo. RNA-sequencing analysis, quantitative real-time PCR, immunoblotting, immunohistochemical analysis, RNA interference assay, and database analysis were conducted to uncover the underlying mechanism of the anti-BC effect of CMHE. Results: We demonstrated the significant inhibition in the proliferative capability of BC cell lines MDA-MB-231 and MCF-7 by CMHE. Moreover, CMHE-induced G0/G1 phase arrest and apoptosis of the above two BC cell lines were also observed. CMHE dramatically repressed the metastatic potential of these two cells in vitro. Additionally, the administration of CMHE remarkably suppressed tumor growth in 4T1 tumor-bearing mice. No obvious toxic or side effects of CMHE administration in mice were noted. Furthermore, immunohistochemical (IHC) analysis demonstrated that CMHE treatment inhibited the proliferative and metastatic abilities of cancer cells, while also promoting apoptosis in the tumor tissues of mice. Based on RNA sequencing analysis, quantitative real-time PCR, immunoblotting, and IHC assay, the administration of CMHE downregulated Cyclin D1/CDK4-Rb signaling pathway in BC. Furthermore, RNA interference assay and database analysis showed that downregulated Cyclin D1/CDK4 signaling cascade participated in the anti-BC activity of CMHE. Conclusion: CMHE treatment resulted in the suppression of BC cell growth through the stimulation of cell cycle arrest at the G0/G1 phase and the induction of apoptotic cell death via the inhibition of the Cyclin D1/CDK4-Rb pathway, thereby enhancing the anti-BC effect of CMHE. CMHE has potential anti-BC effects, particularly in those harboring aberrant activation of Cyclin D1/CDK4-Rb signaling.

MRG15 aggravates sepsis-related liver injury by promoting PCSK9 synthesis and secretion.

OBJECTIVE: Disorders of lipid oxidation play an important role in organ damage, and lipid metabolites are associated with inflammation and coagulation dysfunction in sepsis. However, the specific molecular mechanism by which lipid metabolism-related proteins regulate sepsis is still unclear. The aim of this study is to investigate the role of mortality factor 4-like protein 1 (MORF4L1, also called MRG15), a hepatic lipid metabolism related gene, in sepsis-induced liver injury. METHODS: In the mouse sepsis models established by cecal ligation and puncture (CLP) and lipopolysaccharide (LPS), the impact of pretreatment with the MRG15 inhibitor argatroban on sepsis-related liver injury was investigated. In the LPS-induced hepatocyte sepsis cell model, the effects of MRG15 overexpression or knockdown on hepatic inflammation and lipid metabolism were studied. Additionally, in a co-culture system of hepatocytes and macrophages, the influence of MRG15 knockdown in hepatocytes on the synthesis and secretion of inflammation-related protein PCSK9 as well as its effect on macrophage activation were examined. RESULTS: Studies have shown that MRG15 expression was increased in septicemia mice and positively correlated with lipid metabolism and inflammation. However, knockdown of MRG15 ameliorates sepsis-induced hepatocyte injury. Increased MRG15 in LPS-stimulated hepatocytes promotes PCSK9 synthesis and secretion, which induces macrophage M1 polarization and exacerbates the inflammatory response. Agatroban, an inhibitor of MRG15, ameliorates sepsis-induced liver injury in mice by inhibiting MRG15-induced lipid metabolism disorders and inflammatory responses. CONCLUSIONS: In sepsis, increased MRG15 expression in hepatocytes leads to disturbed hepatic lipid metabolism and induces macrophage M1 polarization by secreting PCSK9, ultimately exacerbating liver injury.

Boswellia carterii n-hexane extract suppresses breast cancer growth via induction of ferroptosis by downregulated GPX4 and upregulated transferrin.

Breast cancer (BC) remains a significant health concern for women globally, prompting the relentless pursuit of novel therapeutic modalities. As a traditional Chinese medicine, Boswellia carterii has been extensively used to treat various cancers, such as BC. However, the anti-BC effect and underlying mechanism of Boswellia carterii remain largely unclear. The aim of this study is to explore the therapeutic effect of Boswellia carterii n-hexane extract (BCHE) against BC as well as its underlying mechanism. The present study showed that BCHE significantly suppressed the viability of human BC cells. Moreover, BCHE exhibited potent anti-BC activity in vivo with no significant toxic effects. Additionally, BCHE induced ferroptosis via increased Transferrin expression and the intracellular accumulation of Fe2+, as well as decreased glutathione peroxidase 4 (GPX4) expression and the upregulation of reactive oxygen species (ROS)-induced lipid peroxidation in BC cells. In vivo experimental results also demonstrated that BCHE effectively induced ferroptosis through GPX4 downregulation and Transferrin upregulation in tumor-bearing mice. Overall, BCHE inhibited the growth of BC cells by inducing ferroptosis mediated by modulating the iron accumulation pathway and the lipid peroxidation pathway. Therefore, BCHE could serve as a potential ferroptosis-targeting drug for treating BC.

Efficient catalytic oxidation of formaldehyde by defective g-C3N4-anchored single-atom Pt: A DFT study.

Indoor volatile formaldehyde is a serious health hazard. The development of low-temperature and efficient nonhomogeneous oxidation catalysts is crucial for protecting human health and the environment but is also quite challenging. Single-atom catalysts (SACs) with active centers and coordination environments that are precisely tunable at the atomic level exhibit excellent catalytic activity in many catalytic fields. Among two-dimensional materials, the nonmagnetic monolayer material g-C3N4 may be a good platform for loading single atoms. In this study, the effect of nitrogen defect formation on the charge distribution of g-C3N4 is discussed in detail using density functional theory (DFT) calculations. The effect of nitrogen defects on the activated molecular oxygen of Pt/C3N4 was systematically revealed by DFT calculations in combination with molecular orbital theory. Two typical reaction mechanisms for the catalytic oxidation of formaldehyde were proposed based on the Eley-Rideal (E-R) mechanism. Pt/C3N4-V3N was more advantageous for path 1, as determined by the activation energy barrier of the rate-determining step and product desorption. Finally, the active centers and chemical structures of Pt/C3N4 and Pt/C3N4-V3N were verified to have good stability at 375 K by determination of the migration energy barriers and ab initio molecular dynamics simulations. Therefore, the formation of N defects can effectively anchor single-atom Pt and provide additional active sites, which in turn activate molecular oxygen to efficiently catalyze the oxidation of formaldehyde. This study provides a better understanding of the mechanism of formaldehyde oxidation by single-atom Pt catalysts and a new idea for the development of Pt as well as other metal-based single-atom oxidation catalysts.

[Comparative analysis of efficacy of different forms of Galli Gigerii Endothelium Corneum on functional dyspepsia in rats based on composition-pharmacodynamics].

A systematic evaluation of the differences in the chemical composition and efficacy of the different forms of Galli Gigerii Endothelium Corneum(GGEC) was conducted based on modern analytical techniques and a functional dyspepsia(FD) rat model, which clarifies the material basis of the digestive efficacy of GGEC. Proteins, enzymes, polysaccharides, amino acids, and flavonoids in GGEC powder and decoction were determined respectively. The total protein of the powder and decoction was 0.06% and 0.65%, respectively, and the pepsin and amylase potency of the powder was 27.03 and 44.05 U·mg~(-1) respectively. The polysaccharide of the decoction was 0.03%, and there was no polysaccharide detected in the powder. The total L-type amino acids in the powder and decoction were 279.81 and 8.27 mg·g~(-1) respectively, and the total flavonoid content was 59.51 µg·g~(-1). Enzymes and flavonoids were not detected in the decoction. The powder significantly reduced nutrient paste viscosity, while the decoction and control group showed no significant reduction in nutrient paste viscosity. FD rat models were prepared by iodoacetamide gavage and irregular diet. The results showed that both powder and decoction significantly increased the gastric emptying effect, small intestinal propulsion rate, digestive enzymes activity, gastrin(GAS), motilin(MTL), ghrelin(GHRL) and reduced vasoactive intestinal peptide(VIP), 3-(2-ammo-nioethyl)-5-hydroxy-1H-indolium maleate(5-HT), and somatostatin(SST) content in rats(P<0.05, P<0.01). Comparison of GGEC decoction and powder administration between groups of the same dosage level showed that gastrointestinal propulsion and serum levels of GAS, GHRL, VIP, and SST in the powder group were significantly superior to those in the decoction and that the gastrointestinal propulsion, as well as serum levels of MTL, GAS, and GHRL were slightly higher than those of the decoction with two times its raw dose, and the serum levels of SST, 5-HT, and VIP in the powder group were slightly lower than those of the decoction with two times its raw dose. In conclusion, both decoction and powder have therapeutic effects on FD, but there is a significant difference between the two effects. Under the same dosage, the digestive efficacy of the powder is significantly better than that of the decoction, and the decoction needs to increase the dosage to compensate for the efficacy. It is hypothesized that the digestive efficacy of the GGEC has a duality, and the digestive active ingredients of the powder may include enzymes and L-type amino acids, while the decoction mainly relies on L-type amino acids to exert its efficacy. This study provides new evidence to investigate the digestive active substances of the GGEC and to improve the effectiveness of the drug in the clinic.

Pipelle Endometrial Sampling With a Full Bladder Compared With Standard Care: A Randomized Controlled Trial.

OBJECTIVE: To compare insertion failure rates for Pipelle endometrial sampling with a full bladder compared with the standard process (not taking into account bladder status) without cervical manipulation. METHODS: A single-masked randomized trial was conducted in a single tertiary care center from July 2021 to January 2022. Two hundred fourteen participants aged 18 years or older who were scheduled for outpatient Pipelle endometrial sampling were randomized: 107 each to having a full bladder (by oral water intake) or standard process (without delayed sampling and bladder status not taken into account). Women with known cervical stenosis, gynecologic malignancy, uterine anomalies, leiomyoma distorting the uterine cavity, acute cervicitis, urge bladder dysfunction, intense anxiety, need for anesthesia or analgesic before the procedure, positive pregnancy test, or previous failed office endometrial sampling were excluded. The primary outcome was the insertion failure rate of endometrial sampling at first attempt. Secondary outcomes were pain during procedure, satisfaction score, analgesia use, procedure duration, and need for cervical manipulation. Factoring in a baseline insertion failure rate of 30.0%, relative risk of 0.45, α of 0.05, 80.0% power, and a dropout rate of 10.0%, we needed 107 participants in each arm. RESULTS: The insertion failure rate was significantly lower in the full bladder group compared with standard process: 25 of 107 (23.4%) compared with 45 of 107 (42.1%) (relative risk 0.56, 95% CI, 0.37-0.84; number needed to treat to benefit 6.0, 95% CI, 3.20-15.70). Pain score (median) during the procedure (interquartile range) was 4 (3-6) compared with 5 (3-8) ( P =.004); patient satisfaction score was 8 (7-9) compared with 7 (4-8) ( P <.001); and mean±SD procedure duration was 3.0±2.4 compared with 4.7±2.9 minutes ( P <.001) for the full bladder and standard process arm, respectively. Other secondary outcomes of cervical laceration, analgesia use, and adequacy of endometrial tissue for histopathologic assessment were not significantly different between groups. CONCLUSION: Pipelle endometrial sampling with a full bladder reduces the initial insertion failure rate, procedure-related pain, and duration of sampling and increases patient satisfaction compared with the standard process. CLINICAL TRIAL REGISTRATION: ISRCTN, ISRCTN33938192.

Density functional theory-based screening of Ti4C3O2-loaded single atoms for efficient selective catalytic oxidation of formaldehyde.

Indoor formaldehyde (HCHO) pollution poses a major risk to human health. Low-temperature catalytic oxidation is an effective method for HCHO removal. The high activity and selectivity of single atomic catalysts provide a possibility for the development of efficient non-precious metal catalysts. In this study, the most stable single-atom catalyst Ti-Ti4C3O2 was screened by density functional theory among many single atomic catalysts with two-dimensional (2D) monolayer Ti4C3O2 as the support. The computational results show that Ti-Ti4C3O2 is highly selective to HCHO and O2 in complex environments. The HCHO oxidation reaction pathways are proposed based on the Eley-Rideal (E-R) and Langmuir-Hinshelwood (L-H) mechanisms. According to the reaction energy and energy span models, the E-R mechanism has a lower maximum energy barrier and higher catalytic efficiency than the L-H mechanism. In addition, the stability of the Ti-Ti4C3O2 structure and active center was verified by diffusion energy barrier and ab initio molecular dynamics simulations. The above results indicate that Ti-Ti4C3O2 is a promising non-precious metal catalyst. The present study provides detailed theoretical insights into the catalytic oxidation of HCHO by Ti-Ti4C3O2, as well as an idea for the development of efficient non-precious metal catalysts based on 2D materials.

The interactions between traditional Chinese medicine and gut microbiota in cancers: Current status and future perspectives.

The gut microbiota, known as the "forgotten organ" and "human second genome," comprises a complex microecosystem. It significantly influences the development of various tumors, including colorectal, liver, stomach, breast, and lung cancers, through both direct and indirect mechanisms. These mechanisms include the "gut-liver" axis, the "lung-intestine" axis, and interactions with the immune system. The intestinal flora exhibits dual roles in cancer, both promoting and suppressing its progression. Traditional Chinese medicine (TCM) can alter cancer progression by regulating the intestinal flora. It modifies the intestinal flora's composition and structure, along with the levels of endogenous metabolites, thus affecting the intestinal barrier, immune system, and overall body metabolism. These actions contribute to TCM's significant antitumor effects. Moreover, the gut microbiota metabolizes TCM components, enhancing their antitumor properties. Therefore, exploring the interaction between TCM and the intestinal flora offers a novel perspective in understanding TCM's antitumor mechanisms. This paper succinctly reviews the association between gut flora and the development of tumors, including colorectal, liver, gastric, breast, and lung cancers. It further examines current research on the interaction between TCM and intestinal flora, with a focus on its antitumor efficacy. It identifies limitations in existing studies and suggests recommendations, providing insights into antitumor drug research and exploring TCM's antitumor effectiveness. Additionally, this paper aims to guide future research on TCM and the gut microbiota in antitumor studies.

Preoperative free access to water compared to fasting for planned cesarean under spinal anesthesia: a randomized controlled trial.

BACKGROUND: Contemporary guidance for preoperative feeding allows solids up to 6 hours and clear fluids up to 2 hours before anesthesia. Clinical trial evidence to support this approach for cesarean delivery is lacking. Many medical practitioners continue to follow conservative policies of no intake from midnight to the time of surgery, especially in pregnant women. OBJECTIVE: This study aimed to evaluate the pragmatic approach of permitting free access to water up to the call to dispatch to the operating theater vs fasting from midnight in preoperative oral intake restriction for planned cesarean delivery under spinal anesthesia on perioperative vomiting and maternal satisfaction. STUDY DESIGN: A randomized controlled trial was conducted in the obstetrical unit of the University of Malaya Medical Centre from October 2020 to May 2022. A total of 504 participants scheduled for planned cesarean delivery were randomized: 252 undergoing preoperative free access to water up to the call to dispatch to the operating theater (intervention group) and 252 undergoing fasting from midnight (fasting arm). The primary outcomes were perioperative vomiting and maternal satisfaction. Analyses were performed using t test, Mann-Whitney U test, and chi-square test, as appropriate. RESULTS: Of note, 9 of 252 patients (3.6%) in the intervention group and 24 of 252 patients (9.5%) in the control group had vomiting at up to 6 hours after completion of cesarean delivery (relative risk, 0.38; 95% confidence interval, 0.18-0.79; P=.007), and the maternal satisfaction scores (0-10 visual numerical rating scale) were 9 (interquartile range, 8-10) in the intervention group and 5 (interquartile range, 3-7) in the control group (P<.001). Assessed before dispatch to the operating theater, feeling of thirst was reported by 69 of 252 patients (27.4%) in the intervention group and 134 of 252 patients (53.2%) in the control group (relative risk, 0.52; 95% confidence interval, 0.41-0.65; P<.001), capillary glucose levels were 4.8±0.7 mmol/L in the intervention group and 4.9±0.8 mmol/L in the control group (P=.048), and preoperative intravenous fluid hydration was commenced in 49 of 252 patients (19.4%) in the intervention group and 76 of 252 patients (30.2%) in the control group (relative risk, 0.65; 95% confidence interval, 0.47-0.88; P=.005). In the operating theater, ketone was detected in the catheterized urine in 38 of 252 patients (15.1%) in the intervention group and 78 of 252 patients (31.0%) in the control group (relative risk, 0.49; 95% confidence interval, 0.25-0.59; P<.001), and the numbers of doses of vasopressors needed to correct hypotension were 2.3±1.7 in the intervention group and 2.7±2.2 in the control (P=.009). The recommendation rates for preoperative oral intake regimen to a friend were 95.2% (240/252) in the intervention group and 39.7% (100/252) in the control group (relative risk, 2.40; 95% confidence interval, 2.06-2.80; P<.001), in favor of free access to water. Other assessed maternal and neonatal outcomes were not different. CONCLUSION: Compared with fasting, free access to water in planned cesarean delivery reduced perioperative vomiting and was strongly favored by women. In addition, several pre- and intraoperative secondary outcomes were improved. However, postcesarean delivery recovery and neonatal outcomes were not different.

Self bladder emptying compared with Foley catheter placement for planned cesarean delivery: a randomized controlled trial.

BACKGROUND: The global cesarean delivery rate is high and continues to increase. A bladder catheter is usually placed for the cesarean delivery because a distended bladder is assumed to be at higher risk of injury during surgery and to compromise surgical field exposure. Preliminary data suggest that self bladder emptying (no catheter) at cesarean delivery may have advantages and be safe. OBJECTIVE: This study aimed to compare the effects of self bladder emptying and indwelling Foley bladder catheterization for planned cesarean delivery on the rate of postpartum urinary retention and maternal satisfaction. STUDY DESIGN: A randomized controlled trial was conducted in a tertiary university hospital from January 10, 2022 to March 22, 2023. A total of 400 participants scheduled for planned cesarean delivery were randomized: 200 each to self bladder emptying or indwelling Foley catheter. The primary outcomes were postpartum urinary retention (overt and covert) and maternal satisfaction with allocated bladder care. Analyses were performed using t test, Mann-Whitney U test, chi-square test, or Fisher exact test, as appropriate. Logistic regression was used to adjust for differences in characteristics. RESULTS: Postpartum urinary retention rates were 1 per 200 (0.6%) and 0 per 200 (P>.99) (a solitary case of covert retention) and maternal satisfaction scores (0-10 visual numerical rating scale), expressed as median (interquartile range) were 9 (8-9.75) and 8 (8-9) (P=.003) in the self bladder emptying and indwelling Foley catheter arms, respectively. Regarding secondary outcomes, time to flatus passage, satisfactory ambulation, urination, satisfactory urination, satisfactory breastfeeding, and postcesarean hospital discharge was quickened in the self bladder emptying group. Pain scores at first urination were decreased and no lower urinary tract symptom was more likely to be reported with self bladder emptying. Surgical field view, operative blood loss, duration of surgery, culture-derived urinary tract infection, postvoid residual volume, and pain score at movement were not different. There was no bladder injury. CONCLUSION: Self bladder emptying increased maternal satisfaction without adversely affecting postpartum urinary retention. Recovery was enhanced and urinary symptoms were improved. The surgeon was not impeded at operation. No safety concern was found.

E3 ubiquitin ligase FBXW11 as a novel inflammatory biomarker is associated with immune infiltration and NF-κB pathway activation in pancreatitis and pancreatic cancer.

BACKGROUND: Pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) is an aggressive disease with an overall poor prognosis. Pancreatitis is a major risk factor for the development of PDAC. Due to the lack of reliable and accurate biomarkers, the diagnosis, treatment, and prognosis of PDAC face great challenges. It is of great significance to elucidate the pathogenesis of PDAC and explore novel inflammatory biomarkers. METHODS: We identified E3 ubiquitin ligases associated with pancreatic inflammation by combining multiple GEO datasets and UbiNet 2.0, and integrating the WGCNA algorithm and Limma R package. A risk score model for PDAC patients was established by using LASSO regression. We investigated the correlation between FBXW11 and immune cell infiltration using CIBERSORT, mMCP-counter, ImmuCellAI-mouse, QUANTISEQ, and TIMER algorithms, based on GEO, ArrayExpress, and TCGA datasets. We used Ubibrowser 2.0 to predict potential substrates for FBXW11. WikiPathway, MSigDB Hallmark, and Elsevier pathway analysis of FBXW11 key substrates were also performed using the EnrichR database. We detected protein expression through IHC, immunofluorescence, and western blot in the cerulein-induced acute pancreatitis mouse model. RESULTS: We first identified that FBXW11 exhibited a clear tendency to gradually increase in normal, pancreatitis, and PDAC patients. The validation analysis revealed that the FBXW11 protein exhibited significantly high expression in cerulein-induced acute pancreatitis mice, with its distribution primarily observed in the cytoplasm. Simultaneously, we developed a risk model utilizing the genes associated with FBXW11 to forecast the outcome of patients with PDAC and the likelihood of pancreatitis advancing to pancreatic cancer. Functional analysis showed that FBXW11, as a novel inflammatory biomarker, had a significant positive correlation with macrophage infiltration and the NF-κB signaling pathway. Finally, the western blot assay of the NF-κB signaling pathway in pancreatic tissues demonstrated that high activation of NF-κB was correlated with high expression of FBXW11. CONCLUSIONS: Our research not only provides evidence for FBXW11 as a novel inflammatory biomarker but also provides new insights into the research and clinical treatment of pancreatic cancer.

Interfering with the AKT/mTOR/STAT3/ID1 signaling axis with usenamine A restrains the proliferative and invasive potential of human hepatocellular carcinoma cells.

BACKGROUND: Usenamine A, a novel natural compound initially isolated from the lichen Usnea longissima, has exhibited promising efficacy against hepatoma in prior investigation. Nevertheless, the underlying mechanisms responsible for its antihepatoma effects remain unclear. Furthermore, the role of the AKT/mechanistic target of the rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3)/inhibitor of differentiation/DNA binding 1 (ID1) signaling axis in hepatocellular carcinoma (HCC), and the potential anti-HCC effects of drugs targeting this pathway are not well understood. METHODS: CCK-8 assay was used to investigate the effects of usenamine A on the proliferation of human HCC cells. Moreover, the effects of usenamine A on the invasion ability of human HCC cells were evaluated by transwell assay. In addition, expression profiling analysis, quantitative real-time PCR, immunoblotting, immunohistochemistry (IHC) analysis, RNAi, immunoprecipitation, and chromatin immunoprecipitation (ChIP) assay were used to explore the effects of usenamine A on the newly identified AKT/mTOR/STAT3/ID1 signaling axis in human HCC cells. RESULTS: Usenamine A inhibited the proliferation and invasion of human HCC cell lines (HepG2 and SK-HEP-1). Through the analysis of gene expression profiling, we identified that usenamine A suppressed the expression of ID1 in human HCC cells. Furthermore, immunoprecipitation experiments revealed that usenamine A facilitated the degradation of the ID1 protein via the ubiquitin-proteasome pathway. Moreover, usenamine A inhibited the activity of STAT3 in human HCC cells. ChIP analysis demonstrated that STAT3 positively regulated ID1 expression at the transcriptional level in human HCC cells. The STAT3/ID1 axis played a role in mediating the anti-proliferative and anti-invasive impacts of usenamine A on human HCC cells. Additionally, usenamine A suppressed the STAT3/ID1 axis through AKT/mTOR signaling in human HCC cells. CONCLUSION: Usenamine A displayed robust anti-HCC potential, partly attributed to its capacity to downregulate the AKT/mTOR/STAT3/ID1 signaling pathway and promote ubiquitin-proteasome-mediated ID1 degradation. Usenamine A has the potential to be developed as a therapeutic agent for HCC cases characterized by abnormal AKT/mTOR/STAT3/ID1 signaling, and targeting the AKT/mTOR/STAT3 signaling pathway may be a viable option for treating patients with HCC exhibiting elevated ID1 expression.

"Bubble-Diode" Breathable Electrodes for Fast Gas Transport.

Bubbles arising from wild gas evolution commonly exist in electrochemical systems, particularly in water electrolysis and rechargeable aqueous batteries (e. g., Zn-air batteries). Substantial energy dissipation occurs due to the obstruction of active sites and ion-conducting pathways by evolving bubbles. Efforts are made to elucidate effective strategies for fast gas transport, most of which focus on minimizing bubble size and facilitating their timely detachment through complex techniques such as constructing super-hydrophilic nano-structure electrodes, flowing electrolytes, and ultrasonic oscillation. Recently, an innovative, facile, and highly efficient method utilizing a breathable electrode design to promote gaseous molecules to the external environment emerges as a promising approach since it avoids remarkable bubble accumulation while remaining free of additional accessories. This paper highlights the origin and evolution of this promising design. Starting with introducing the basic concept of traditional breathable electrodes based on hydrophobic polymer networks and discussing the current progress made in underlying mechanisms, a detailed description of the advanced design inspired by a "bubble-diode" concept with superior breathability follows. This Concept aims to contribute to a deep understanding of this technology and paves the way for further advancements in this renewable energy era.

Reparative effect of different dietary additives on soybean meal-induced intestinal injury in yellow drum (Nibea albiflora).

Soybean meal (SBM) is an acceptable replacement for unsustainable marine fish meal (FM) in aquaculture. However, we previously reported that high dietary SBM supplementation causes intestinal inflammatory injury in yellow drum (Nibea albiflora). Accordingly, a 4-week SBM-induced enteritis (SBMIE) in yellow drum trial was conducted first, followed by a 4-week additive-supplemented reparative experiment to evaluate the reparative effect of five additives on SBMIE in yellow drum. The control diet comprised 50% FM protein substituted with SBM. The additive-supplemented diet was added with 0.02% curcumin (SBMC), 0.05% berberine (SBM-BBR), 0.5% tea polyphenols (SBM-TPS), 1% taurine (SBM-TAU), or 0.8% glutamine (SBM-GLU) based on the control diet, respectively. The weight gain (WG), specific growth rate (SGR), feed efficiency ratio (FER), and survival rate (SR) of fish fed the additive-supplemented diets were significantly higher than those of fish fed the SBM diet. The WG, SGR, and FER of fish fed the SBMC, SBM-GLU and SBM-TAU diets were significantly higher than those of fish fed other diets. Moreover, fish fed the additive-supplemented diets SBMC and SBM-GLU, exhibited significantly increased intestinal villus height (IVH), intestinal muscular thickness (IMRT), and intestinal mucosal thickness (IMLT) and significantly decreased crypt depth (CD) in comparison with those fed the SBM diets. The relative expression of intestinal tight junction factors (ocln, zo1), cytoskeletal factors (f-actin, arp2/3), and anti-inflammatory cytokines (il10, tgfb) mRNA was remarkably elevated in fish fed additive-supplemented diets than those of fish fed the SBM diet. Whereas, the relative expression of intestinal myosin light chain kinase (mlck) and pro-inflammatory cytokines (il1, il6, tnfa) mRNA was markedly lower in fish fed the additive-supplemented diets. The highest relative expression of intestinal ocln, f-actin, and arp2/3 and the lowest relative expression of intestinal mlck were found in fish fed the SBMC diet. Hence, all five dietary additives effectively repaired the intestinal injury induced by SBM, with curcumin exhibiting the strongest repair effect for SBMIE in yellow drum.

Biomimetic and bioinspired nano-platforms for cancer vaccine development.

The advent of immunotherapy has revolutionized the treating modalities of cancer. Cancer vaccine, aiming to harness the host immune system to induce a tumor-specific killing effect, holds great promises for its broad patient coverage, high safety, and combination potentials. Despite promising, the clinical translation of cancer vaccines faces obstacles including the lack of potency, limited options of tumor antigens and adjuvants, and immunosuppressive tumor microenvironment. Biomimetic and bioinspired nanotechnology provides new impetus for the designing concepts of cancer vaccines. Through mimicking the stealth coating, pathogen recognition pattern, tissue tropism of pathogen, and other irreplaceable properties from nature, biomimetic and bioinspired cancer vaccines could gain functions such as longstanding, targeting, self-adjuvanting, and on-demand cargo release. The specific behavior and endogenous molecules of each type of living entity (cell or microorganism) offer unique features to cancer vaccines to address specific needs for immunotherapy. In this review, the strategies inspired by eukaryotic cells, bacteria, and viruses will be overviewed for advancing cancer vaccine development. Our insights into the future cancer vaccine development will be shared at the end for expediting the clinical translation.

Thermal treatment enhances the resisting exercise fatigue effect of Phyllanthus emblica L.: novel evidence from tannin conversion in vitro, metabolomics, and gut microbiota community analysis.

Polyphenols are the main component of Phyllanthus emblica (PE). However, polyphenols are so easy to transform that it is unknown that how drying methods driven by heating affect the anti-fatigue effect of PE. This manuscript investigated the effects of five drying methods on the chemical composition transformation and anti-fatigue of PE, and discussed the action mechanism. The results suggested that the anti-fatigue effect of PE with hot-air-dried at 100 °C was the best, which was as 1.63 times as that with freeze-drying. Ellagic acid (EA) may be a key component of PE in anti-fatigue, and its mechanism of action may be related to regulating intestinal microbiota, protecting mitochondria, and regulating energy metabolism. This study first revealed the thermal transformation of polyphenols in PE, found the most effective strategy for enhancing the anti-fatigue function, and explores its action mechanism.

A review on the research progress of traditional Chinese medicine with anti-cancer effect targeting ferroptosis.

Ferroptosis is a non-apoptotic form of regulated cell death characterized by iron-dependent lipid peroxidation. It can be triggered by various mechanisms, including the glutathione peroxidase 4 (GPX4)-glutathione (GSH) axis, iron metabolism, lipid metabolism, the GTP cyclohydrolase 1 (GCH1)-tetrahydrobiopterin (BH4) pathway, and the ferroptosis suppressor protein 1 (FSP1)-coenzyme Q10 axis. The redox balance is disrupted when ferroptosis occurs in cells, which is fatal to cancer cells. Additionally, some tumor-associated genes are involved in ferroptosis. Hence, targeting ferroptosis might be an effective strategy for treating cancer. Several small-molecule compounds exhibit anti-tumor effects through ferroptosis, including sorafenib and altretamine, which induce ferroptosis by inhibiting System-Xc and GPX4 respectively, but many problems, such as poor druggability, still exist. Some studies have shown that many traditional Chinese medicine (TCM) induce ferroptosis by inhibiting GPX4, solute carrier family 7 member 11 (SLC7A11), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), or by increasing the expression of Acyl-CoA synthetase long-chain family member 4 (ACSL4), transferrin (TF), and transferrin receptor 1 (TFR1). These changes can lead to the lysosomal degradation of ferritin, accumulation of iron, lipid peroxidation and the production of reactive oxygen species (ROS), which in turn can promote anti-tumor activities or synergistic effects with chemotherapeutic drugs. In this study, we elucidated the underlying mechanisms of ferroptosis, and the anti-tumor pharmacology of TCM targeting ferroptosis including prescriptions, Chinese herbs, extracts, and natural compounds. Our findings might act as valuable reference for research on anti-tumor drugs targeting ferroptosis, especially those drugs developed from TCM.

Zyxin promotes hepatocellular carcinoma progression via the activation of AKT/mTOR signaling pathway.

Hepatocellular carcinoma (HCC) is a common malignancy that is driven by multiple genes and pathways. The aim of this study was to investigate the role and specific mechanism of the actin-interacting protein zyxin (ZYX) in HCC. We found that the expression of ZYX was significantly higher in HCC tissues compared to that in normal liver tissues. In addition, overexpression of ZYX in hepatoma cell lines (PLC/PRF/5, HCCLM3) enhanced their proliferation, migration and invasion, whereas ZYX knockdown had the opposite effects (SK HEP-1, Huh-7). Furthermore, the change in the expression levels of ZYX also altered that of proteins related to cell cycle, migration and invasion. Similar results were obtained with xenograft models. The AKT/mTOR signaling pathway is one of the key mediators of cancer development. While ZYX overexpression upregulated the levels of phosphorylated AKT/mTOR proteins, its knockdown had the opposite effect. In addition, the AKT inhibitor MK2206 neutralized the pro-oncogenic effects of ZYX on the HCC cells, whereas the AKT activator SC79 restored the proliferation, migration and invasion of HCC cells with ZYX knockdown. Taken together, ZYX promotes the malignant progression of HCC by activating AKT/mTOR signaling pathway, and is a potential therapeutic target in HCC.

The Role of Traditional Chinese Medicine in Cancer Immunotherapy: Current Status and Future Directions.

The tumor microenvironment (TME) plays an important role in the development of tumors. Immunoregulatory cells and cytokines facilitate cancer cells to avoid immune surveillance. Overexpression of immune checkpoint molecules such as CTLA-4 and PD-1/PD-L1 inhibits immune function and enables cancer cells to avoid clearance by the immune system. Thus, minimizing tumor immunosuppression could be an important strategy for cancer therapy. Currently, many immune checkpoint-targeted drugs, such as PD-1/PD-L1 inhibitors, have been approved for marketing and have shown unique advantages in the clinical treatment of cancers. The concept of "strengthening resistance to eliminate pathogenic factors" in traditional Chinese medicine (TCM) is consistent with the immunotherapy of cancer. According to previous studies, the role of TCM in tumor immunotherapy is mainly associated with the positive regulation of natural killer cells, CD8/CD4 T cells, dendritic cells, M2 macrophages, interleukin-2, tumor necrosis factor-[Formula: see text], and IFN-[Formula: see text], as well as with the negative regulation of Tregs, myeloid-derived suppressor cells, cancer-associated fibroblasts, PD-1/PD-L1, transforming growth factor-[Formula: see text], and tumor necrosis factor-[Formula: see text]. This paper summarizes the current research on the effect of TCM targeting the TME, and further introduces the research progress on studying the effects of TCM on immune checkpoints. Modern pharmacological studies have demonstrated that TCM can directly or indirectly affect the TME by inhibiting the overexpression of immune checkpoint molecules and enhancing the efficacy of tumor immunotherapy. TCM with immunomodulatory stimulation could be the key factor to achieve benefits from immunotherapy for patients with non-inflammatory, or "cold", tumors.