Property Enhancement of Waste Printed Circuit Boards Powders Reinforced Polypropylene by In Situ Magnesium Hydroxide Impregnation from Waste Lye.

Using alkali pretreatment can effectively remove residual variable-valence metals from non-metallic powder (WPCBP) in waste printed circuit boards. However, substantial amounts of waste lye are generated, which causes secondary pollution. On this basis, this study innovatively utilized waste alkali lye to prepare nano-magnesium hydroxide. When the dispersant polyethylene glycol 6000 was used at a dosage of 3 wt.% of the theoretical yield of magnesium hydroxide, the synthesized nano-magnesium hydroxide exhibited well-defined crystallinity, good thermal stability and uniform particle size distribution, with a median diameter of 197 nm. Furthermore, the in situ method was selected to prepare WPCBP/Mg(OH)2 hybrid filler (MW) and the combustion behavior, thermal and mechanical properties of PP blends filled with MW were evaluated. The combustion behavior of the PP/MW blends increased with the increasing hybrid ratio of Mg(OH)2, and the MW hybrid filler reinforced PP blends showed better thermal and mechanical properties compared to the PP/WPCBP blends. Furthermore, the dynamic mechanical properties of the PP/MW blends were also increased due to the improved interfacial adhesion between the MW fillers and PP matrix. This method demonstrated high economic and environmental value, providing a new direction for the high value-added utilization of WPCBP.

Inhibition of SAT1 alleviates chondrocyte inflammation and ferroptosis by repressing ALOX15 expression and activating the Nrf2 pathway.

Aims: Osteoarthritis (OA) is the most common chronic pathema of human joints. The pathogenesis is complex, involving physiological and mechanical factors. In previous studies, we found that ferroptosis is intimately related to OA, while the role of Sat1 in chondrocyte ferroptosis and OA, as well as the underlying mechanism, remains unclear. Methods: In this study, interleukin-1ß (IL-1ß) was used to simulate inflammation and Erastin was used to simulate ferroptosis in vitro. We used small interfering RNA (siRNA) to knock down the spermidine/spermine N1-acetyltransferase 1 (Sat1) and arachidonate 15-lipoxygenase (Alox15), and examined damage-associated events including inflammation, ferroptosis, and oxidative stress of chondrocytes. In addition, a destabilization of the medial meniscus (DMM) mouse model of OA induced by surgery was established to investigate the role of Sat1 inhibition in OA progression. Results: The results showed that inhibition of Sat1 expression can reduce inflammation, ferroptosis changes, reactive oxygen species (ROS) level, and lipid-ROS accumulation induced by IL-1ß and Erastin. Knockdown of Sat1 promotes nuclear factor-E2-related factor 2 (Nrf2) signalling. Additionally, knockdown Alox15 can alleviate the inflammation-related protein expression induced by IL-1ß and ferroptosis-related protein expression induced by Erastin. Furthermore, knockdown Nrf2 can reverse these protein expression alterations. Finally, intra-articular injection of diminazene aceturate (DA), an inhibitor of Sat1, enhanced type II collagen (collagen II) and increased Sat1 and Alox15 expression. Conclusion: Our results demonstrate that inhibition of Sat1 could alleviate chondrocyte ferroptosis and inflammation by downregulating Alox15 activating the Nrf2 system, and delaying the progression of OA. These findings suggest that Sat1 provides a new approach for studying and treating OA.

Perceived Determinants of Health-Related Behaviors Among Patients with Coronary Heart Disease After Percutaneous Coronary Intervention: A Longitudinal Qualitative Study.

Purpose: Studies had reported some influencing factors of health behavior among patients with coronary heart disease(CHD) after percutaneous coronary intervention(PCI). However, considering that human perceptions are complex, unrestricted and dynamically changing. A longitudinal qualitative study was conducted to explore the determinants of health-related behaviors of patients after PCI and dynamic changes of these determinants at the 1st, 3rd, and 6th months. Patients and Methods: Using purposive sampling, 18 patients undergoing PCI were interviewed. The conventional content analysis method was used to identify categories and subcategories. Semi-structured, face-to-face or telephone in-depth interviews were conducted at the cardiology unit of a tertiary referral hospital in Yunnan Province, China from March 2022 to January 2023. Results: Seven categories with some subcategories were constructed from the data, categorized into three domains. Firstly, individual factors include (i) Personal coping with healthy lifestyle requirements (tried but failed; I can do it), (ii) individual perception and feeling toward disease (knowing about the disease; belief of cure; fears of relapse), and (iii) personal benefits (improved health; meaning of life). Secondly, social factors include (i) social facilitators (family resources; healthcare support), (ii) social barriers (inconvenient medical care service; conflicting information). Finally, cultural factors include (i) way of living (dietary habits; key roles of yan (cigarette) and jiu (alcohol) in Chinese society), (ii) way of thinking (fatalism and Confucian familism). Conclusion: The determinants of health-related behaviors of patients after PCI are multifaceted and dynamic. Different interventions should be formulated to promote patients' adherence to health behaviors. Moreover, priority should be given to the impact of traditional Chinese philosophy on the health behaviors of patients after PCI, and the health promotion program for these patients should be culturally sensitive. In addition, future research should further explore the determinants of health behaviors among diverse ethnic minorities after PCI, which has not been fully inquired in this study.

DMT1-mediated iron overload accelerates cartilage degeneration in Hemophilic Arthropathy through the mtDNA-cGAS-STING axis.

INTRODUCTION: Excess iron contributes to Hemophilic Arthropathy (HA) development. Divalent metal transporter 1 (DMT1) delivers iron into the cytoplasm, thus regulating iron homeostasis. OBJECTIVES: We aimed to investigate whether DMT1-mediated iron homeostasis is involved in bleeding-induced cartilage degeneration and the molecular mechanisms underlying iron overload-induced chondrocyte damage. METHODS: This study established an in vivo HA model by puncturing knee joints of coagulation factor VIII gene knockout mice with a needle, and mimicked iron overload conditions in vitro by treatment of Ferric ammonium citrate (FAC). RESULTS: We demonstrated that blood exposure caused iron overload and cartilage degeneration, as well as elevated expression of DMT1. Furthermore, DMT1 silencing alleviated blood-induced iron overload and cartilage degeneration. In hemophilic mice, articular cartilage degeneration was also suppressed by intro-articularly injection of DMT1 adeno-associated virus 9 (AAV9). Mechanistically, RNA-sequencing analysis indicated the association between iron overload and cGAS-STING pathway. Further, iron overload triggered mtDNA-cGAS-STING pathway activation, which could be effectively mitigated by DMT1 silencing. Additionally, we discovered that RU.521, a potent Cyclic GMP-AMP Synthase (cGAS) inhibitor, successfully suppressed the downward cascades of cGAS-STING, thereby protecting against chondrocyte damage. CONCLUSION: Taken together, DMT1-mediated iron overload promotes chondrocyte damage and murine HA development, and targeted DMT1 may provide therapeutic and preventive approaches in HA.

pH-Responsive Hyaluronic Acid Nanomicelles for Photodynamic /Chemodynamic Synergistic Therapy Trigger Immunogenicity and Oxygenation.

Cancer metastasis and invasion are closely related to tumor cell immunosuppression and intracellular hypoxia. Activation of immunogenicity and intracellular oxygenation are effective strategies for cancer treatment. In this study, multifunctional nanomicelle hyaluronic acid and cinnamaldehyde is self-assembled into nanomicelles (HPCNPs) were constructed for immunotherapy and tumor cell oxygenation. The Schiff base was constructed of HPCNPs with pyropheophorbide a-Cu (PPa-Cu). HPCNPs are concentrated in tumor sites under the guidance of CD44 proteins, and under the stimulation of tumor environment (weakly acidic), the Schiff base is destroyed to release free PPa. HPCNPs with photodynamic therapeutic functions and chemokinetic therapeutic functions produce a large number of reactive oxygen species (1O2 and •OH) under exogenous (laser) and endogenous (H2O2) stimulations, causing cell damage, and then inducing immunogenic cell death (ICD). ICD markers (CRT and ATP) and immunoactivity markers (IL-2 and CD8) were characterized by immunofluorescence. Downregulation of Arg1 protein proved that the tumor microenvironment changed from immunosuppressive type (M2) to antitumor type (M1). The oxidation of glutathione by HPCNP cascades to amplify the concentration of reactive oxygen species. In situ oxygenation by HPCNPs based on a Fenton-like reaction improves the intracellular oxygen level. In vitro and in vivo experiments demonstrated that HPCNPs combined with an immune checkpoint blocker (α-PD-L1) effectively ablated primary tumors, effectively inhibited the growth of distal tumors, and increased the oxygen level in tumor cells.

Effects of Doxorubicin, Epirubicin, and Liposomal Doxorubicin (Anthracycline) on cardiac function in patients with osteosarcoma and their influencing factors.

OBJECTIVE: The objective of this study was to investigate the impact of Doxorubicin, Epirubicin, and Liposomal Doxorubicin (Anthracycline) on cardiac function in osteosarcoma patients and analyze the factors influencing this effect. METHODS: A retrospective study was conducted on 165 osteosarcoma patients admitted to our hospital from January 2020 to December 2022. Based on the chemotherapy regimen, the patients were divided into two groups: the control group (n = 62) treated with Cisplatin and cyclophosphamide, and the observation group (n = 103) treated with Doxorubicin, Epirubicin, and Liposomal Doxorubicin (Anthracycline). The general records of both groups were analyzed, and left ventricular ejection fraction (LVEF) was evaluated through echocardiography before and after chemotherapy. Blood cTnT and CK-MB levels were measured using immunoluminescence. The incidence of adverse reactions during chemotherapy was also analyzed. Univariate analysis was performed to identify patients with cardiotoxic events, and multiple logistic regression analysis was done to study the effects of Doxorubicin, Epirubicin, Liposomal Doxorubicin, and their dosages on cardiotoxicity in patients. RESULTS: The general records between the two groups showed no significant differences (P > 0.05). However, at the fourth cycle of chemotherapy, the observation group exhibited a lower LVEF (P < 0.05), and a higher percentage of LVEF decrease compared to the control group (P < 0.05). Moreover, the observation group had higher levels of blood cTnT and CK-MB (P < 0.05). The incidence of cardiotoxicity in the observation group was also higher (P < 0.05), but no significant differences were seen in other adverse reaction rates (P > 0.05). The occurrence of cardiotoxicity was found to be related to the choice and dosage of chemotherapy drugs (P < 0.05), but not significantly correlated with age, sex, and mediastinal irradiation in patients (P > 0.05). Furthermore, the use of Doxorubicin, Epirubicin, and Liposomal Doxorubicin in chemotherapy, as well as an increase in their dosages, was found to elevate the risk of cardiotoxicity in osteosarcoma patients (P < 0.05). However, age, sex, and mediastinal radiation were not significantly associated with cardiotoxicity in osteosarcoma patients (P > 0.05). CONCLUSION: We demonstrated that Doxorubicin, Epirubicin, Liposomal Doxorubicin (Anthracycline), and other drugs adversely affected cardiac function in osteosarcoma patients, increasing the risk of cardiac toxicity. Therefore, close monitoring of cardiac function during chemotherapy is crucial, and timely adjustments to the chemotherapy regimen are necessary. In addition, rational control of drug selection and dosage is essential to minimize the occurrence of cardiac toxicity.

Label-free assessment of pathological changes in pancreatic intraepithelial neoplasia by biomedical multiphoton microscopy.

Pancreatic intraepithelial neoplasia (PanIN) is the most common precursor lesion that has the potential to progress to invasive pancreatic cancer, and early and rapid detection may offer patients a chance for treatment before the development of invasive carcinoma. Therefore, the identification of PanIN holds significant clinical importance. In this study, we first used multiphoton microscopy (MPM) combining two-photon excitation fluorescence and second-harmonic generation imaging to label-free detect PanIN and attempted to differentiate between normal pancreatic ducts and different grades of PanIN. Then, we also developed an automatic image processing strategy to extract eight morphological features of collagen fibers from MPM images to quantify the changes in collagen fibers surrounding the ducts. Experimental results demonstrate that the combination of MPM and quantitative information can accurately identify normal pancreatic ducts and different grades of PanIN. This study may contribute to the rapid diagnosis of pancreatic diseases and may lay the foundation for further clinical application of MPM.

MiR-548t-5p regulates pancreatic ductal adenocarcinoma metastasis through an IL-33-dependent crosstalk between cancer cells and M2 macrophages.

IL-33 has been associated with pro- and anticancer functions in cancer. However, its role in pancreatic cancer metastasis remains unknown. This study aimed to explore the role of miR-548t-5p/IL-33 axis in the metastasis of pancreatic cancer. Luciferase activity assay, qRT-PCR, Western blot and ELISA were performed to prove whether IL-33 is the target of miR-548t-5p. In vivo metastasis assay and cellular transwell assay were performed to explore the role of miR-548t-5p/IL-33 axis in the invasion and metastasis of pancreatic cancer. Co-culture experiments and immunohistochemistry were performed to observe whether IL-33 affects cell invasion and metastasis dependent on the involvement of M2 macrophages. THP-1 cell induction experiment and flow cytometry were performed to explore the effect of IL-33 on macrophage polarization. CCK-8, colony formation, cell apoptosis, cell cycle, cell wound healing and transwell assay were performed to investigate the effect of IL-33 induced M2 macrophages on cell malignant biological behavior by coculturing pancreatic cancer cells with the conditioned medium (CM) from macrophages. We found that miR-548t-5p regulated the expression and secretion of IL-33 in pancreatic cancer cells by directly targeting IL-33 mRNA. IL-33 secreted by cancer cells promoted the recruitment and activation of macrophages to a M2-like phenotype. In turn, IL-33 induced M2 macrophages promoted the migration and invasion of cancer cells. Moreover, IL-33 affected pancreatic cancer cell invasion dependent on the involvement of M2 macrophages in the co-culture system. Thus, our study suggested that manipulation of this IL-33-dependent crosstalk has a therapeutic potential for the treatment of pancreatic cancer metastasis.

Effect of different loads on facet joint motion during lumbar lateral bending in sitting position.

OBJECTIVE: To study the effect of weight-bearing on lumbar facet joint during lateral bending in sitting position. METHODS: Ten normal healthy people (5 males and 5 females) aged 25-39 years (mean 32 ± 4.29 years) were recruited. CT scanning was used to reconstruct the lumbar spine model, and then dual fluoroscopic image system (DFIS) was used to restore the lumbar facet joint movement in sitting position. Finally, the lumbar facet joint translation distance and rotation angle were measured. RESULTS: In L3-4 level, the displacement of right facet joint in Y-axis was the smallest at 0.05 ± 0.40 mm, the displacement of 0 kg left facet joint in X-axis was the largest at 1.68 ± 0.85 mm, and the rotation angle was - 0.57 ± 1.43° to 5.66 ± 2.70° at 10 kg; in L4-5 level, the displacement of right facet joint in Y-axis was the smallest at 10 kg, - 0.13 ± 0.91 mm, and the displacement of left facet joint in Z-axis was the largest at - 2.11 ± 0.88 mm, and the rotation angle was 0.21 ± 2.14° to 7.89 ± 2.59° at 10 kg; in L5-S1 level, the displacement of right facet joint in Y-axis was the smallest at 10 kg, - 0.17 ± 1.10 mm, and the displacement of 0 kg left facet joint in X-axis was the largest at 2.19 ± 2.28 mm, and the rotation angle was 0.03 ± 2.02° to 3.98 ± 0.37°. CONCLUSION: In sitting position, weight-bearing has certain influence on the displacement of facet joints during lumbar lateral bending movement, and this influence occurs simultaneously in translation and rotation; the left and right facet joints are not symmetrical during lumbar lateral bending movement.

A qualitative study on patients' and health care professionals' perspectives regarding care delivered during CIED operation.

BACKGROUND: Cardiac implantable electronic devices (CIEDs) has proven to be an invaluable tool in the practice of cardiology. Patients who have undergone CIED surgery with local anesthesia may result in fear, insecurity and suffering. Some studies have put efforts on ways to improve intraoperative experience of patients with local anesthesia, but researches concerning experiences of CIED patients during surgery is in its infancy. METHODS: Based on semi-structured and in-depth interviews, a qualitative design was conducted in a tertiary general hospital in China from May 2022 to July 2023.Purposeful sampling of 17 patients received CIED surgery and 20 medical staff were interviewed. Thematic analysis with an inductive approach was used to identify dominant themes. RESULTS: Four themes emerged from the data: (1) Safety and success is priority; (2) Humanistic Caring is a must yet be lacking; (3) Paradox of surgery information given; (4) Ways to improve surgery experiences in the operation. CONCLUSIONS: Intraoperative care is significant for CIED surgery. To improve care experience during surgery, healthcare professionals should pay attention to patients' safety and the factors that affecting humanistic caring in clinical practice. In addition, information support should consider information-seeking styles and personal needs. Besides, the four approaches presented in this study are effective to improve the intraoperative care experience.

Evaluating combined bevacizumab and XELOX in advanced colorectal cancer: Serum markers carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 199 analysis.

BACKGROUND: Colorectal cancer ranks third and second among common and fatal cancers. The treatment of metastatic colorectal cancer (mCRC) is generally based on XELOX in clinical practice, which includes capecitabine (CAP) and oxaliplatin. Serum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125 and CA199 are prognostic factors for various tumors. AIM: To investigate evaluating combined bevacizumab (BEV) and XELOX in advanced colorectal cancer: Serum markers CEA, CA125, CA199 analysis. METHODS: In this retrospective study, a total of 94 elderly patients diagnosed with mCRC were recruited and subsequently categorized into two groups based on the distinct treatment modalities they received. The control group was treated with XELOX plus CAP (n = 47), while the observation group was treated with XELOX plus CAP and BEV (n = 47). Several indexes were assessed in both groups, including disease control rate (DCR), incidence of adverse effects, serum marker levels (CEA, CA125, and CA19) and progression-free survival (PFS). RESULTS: After 9 wk of treatment, the serum levels of CEA, CA199 and CA125 in the observation group were significantly lower than those in the control group (P < 0.05). Moreover, the PFS of the observation group (9.12 ± 0.90 mo) was significantly longer than that of the control group (6.49 ± 0.64 mo). Meanwhile, there was no statistically significant difference in the incidence of adverse reactions and DCR between the two groups during maintenance therapy (P > 0.05). CONCLUSION: On the basis of XELOX treatment, the combination of BEV and CAP can reduce serum tumor marker levels and prolong PFS in patients with mCRC.

Ethnobotanical study on medicinal plants used by the Yi people in Xiaoliangshan, Yunnan Province, SW China.

ETHNOPHARMACOLOGICAL RELEVANCE: The Yi people in the Xiaoliangshan region in southwest China have a unique practice of combining ritual treatment and traditional medicine to care for patients. Despite increasing urbanization in the area, they have managed to preserve their distinctive lifestyle and extensive knowledge of traditional medicinal plants, setting them apart from other regions. However, there is a lack of systematic documentation on the knowledge of traditional medicinal plants used by the Yi people in Xiaoliangshan. AIM OF THE STUDY: This research aims to achieve the following objectives: 1. Document the diversity of medicinal plants used by the Yi people and explore their therapeutic usages. 2. Evaluate and analyze the main types of diseases with a high incidence in the local area and identify the types of medicinal plants used to treat these diseases. 3. Explore the underlying geographical and human factors influencing both disease prevalence and medicinal plant usage. METHODS: Ethnobotanical research methods were used to record and analyze the medicinal plants used by the Yi in Xiaoliangshan. Experts identified all plant specimens collected during ethnobotanical field surveys. The types of diseases treated by medicinal plants were classified according to the International Classification of Primary Care -2nd. RESULTS: A total of 125 medicinal plants were recorded after interviewing 193 participants. Of the medicinal plants identified, those with over 100 use reports were Paris polyphylla (202 use reports), Taxillus sutchuenensis (183), Artemisia indica (149), and Papaver somniferum (113). A total of 14 disease categories were recorded, with those related to the following categories having higher Informant Consensus factor values (ICF ≥0.85): Pregnancy, Childbearing, Family Planning, General and Unspecified, Urological, Respiratory, Musculoskeletal, and Skin. The highest quantity of medicinal plants is utilized to improve specific diseases and health problems, namely those related to Digestion, Skin, and Musculoskeletal. Fewer plant species were utilized for diseases or health issues associated with Eyes, Psychological, or Pregnancy, Childbearing, and Family Planning. The use reports from the informants also revealed how some medicinal plants are used to treat a variety of diseases or health issues. For instance, Malva pusilla is used for inducing abortion, treating postpartum hemorrhage, and joint sprains; Artemisia indica is used for treating malaria; Argentina lineata is used to remedy tuberculosis and malaria. Taxillus sutchuenensis is used for dealing with cold, pneumonia, and other ailments. CONCLUSIONS: The Yi people in Xiaoliangshan have a rich knowledge of traditional medicinal plants. Decoction and wine brewing are the most common processing methods used for these plants, which are utilized to treat a wide range of diseases. The characteristics of the medicinal use of the Yi people reflects the alpine mountainous environment in which they live, and their medical practices are closely related to traditional healing culture. This study enhances our understanding of the Yi traditional medicine via documentation and offers a valuable reference for future research and the development of new drugs.

Sorafenib plus triplet therapy with venetoclax, azacitidine and homoharringtonine for refractory/relapsed acute myeloid leukemia with FLT3-ITD: A multicenter phase 2 study.

BACKGROUND: Patients with relapsed or refractory acute myeloid leukemia (R/R AML) and FLT3-internal tandem duplication (FLT3-ITD) respond infrequently to salvage chemotherapy. OBJECTIVE: To investigate the efficacy of sorafenib plus triplet therapy with venetoclax, azacitidine, and homoharringtonine (VAH) as a salvage therapy in this population. METHODS: This multicenter, single-arm, phase 2 study was conducted at 12 hospitals across China. Eligible patients had R/R AML with FLT3-ITD (aged 18-65 years) who were treated with VAH. The primary endpoint was composite complete remission (CRc) after two cycles. Secondary outcomes included the overall response rate (ORR), safety, and survival. RESULTS: Between July 9, 2020, and March 19, 2022, 58 patients were assessed for eligibility, 51 of whom were enrolled. The median patient age was 47 years (interquartile range [IQR] 31-57). CRc was 76.5% with ORR of 82.4%. At a median follow-up of 17.7 months (IQR, 8.7-24.7), the median duration of CRc was not reached (NR), overall survival was 18.1 months (95% confidence interval [CI], 11.8-NR) and event-free survival was 11.4 months (95% CI, 5.6-NR). Grade 3 or 4 adverse events occurring in ≥10% of patients included neutropenia in 47 (92.2%), thrombocytopenia in 41 (80.4%), anemia in 35 (68.6%), febrile neutropenia in 29 (56.9%), pneumonia in 13 (25.5%), and sepsis in 6 (11.8%) patients. Treatment-related death occurred in two (3.9%) patients. CONCLUSIONS: The sorafenib plus VAH regimen was well tolerated and highly active against R/R AML with FLT3-ITD. This regimen may be a suitable therapeutic option for this population, but larger population trials are needed to be explored. TRIAL REGISTRATION: Clinical Trials Registry: NCT04424147.

Bariatric surgery induces pancreatic cell transdifferentiation as indicated by single-cell transcriptomics in Zucker diabetic rats.

AIMS: Bariatric surgery results in rapid recovery of glucose control in subjects with type 2 diabetes mellitus. However, the underlying mechanisms are still largely unknown. The present study aims to clarify how bariatric surgery modifies pancreatic cell subgroup differentiation and transformation in the single-cell RNA level. METHODS: Male, 8-week-old Zucker diabetic fatty (ZDF) rats with obesity and diabetes phenotypes were randomized into sleeve gastrectomy (Sleeve, n = 9), Roux-en-Y gastric bypass (RYGB, n = 9), and Sham (n = 7) groups. Two weeks after surgery, the pancreas specimen was further analyzed using single-cell RNA-sequencing technique. RESULTS: Two weeks after surgery, compared to the Sham group, the metabolic parameters including fasting plasma glucose, plasma insulin, and oral glucose tolerance test values were dramatically improved after RYGB and Sleeve procedures (p < .05) as predicted. In addition, RYGB and Sleeve groups increased the proportion of pancreatic ß cells and reduced the ratio of α cells. Two multiple hormone-expressing cells were identified, the Gcg+/Ppy + and Ins+/Gcg+/Ppy + cells. The pancreatic Ins+/Gcg+/Ppy + cells were defined for the first time, and further investigation indicates similarities with α and ß cells, with unique gene expression patterns, which implies that pancreatic cell transdifferentiation occurs following bariatric surgery. CONCLUSIONS: For the first time, using the single-cell transcriptome map of ZDF rats, we reported a comprehensive characterization of the heterogeneity and differentiation of pancreatic endocrinal cells after bariatric surgery, which may contribute to the underlying mechanisms. Further studies will be needed to elucidate these results.

ATGL promotes colorectal cancer growth by regulating autophagy process and SIRT1 expression.

CRC is a common malignant tumor in the gastrointestinal tract, and its incidence has increased significantly in recent years. Several studies revealed that lipid metabolism reprogramming contributed to tumorigenicity and malignancy by interfering with energy production, membrane formation, and signal transduction in cancers. ATGL is a kind of hydroxy fatty acid ester of fatty acid synthase, and its role in tumor remains controversial. We compared levels of adipose triglyceride lipase (ATGL) in human CRC specimens to adjacent specimens. To validate the effect of ATGL on the proliferation ability of CRC, CCK8 assay and clone formation assay were performed. To evaluate whether autophagy process takes part in the effect of ATGL on CRC proliferation, the value of LC3-II/LC3-I was detected by western blot and we blocked the SIRT1 to detect value of LC3-II/LC3-I and p62 via western blot. In the end, we detected the value of SIRT1 in CRC specimens. We found that ATGL showed high expression in CRC and positively correlated with clinical stage, indicating poor prognosis of CRC. Moreover, ATGL significantly promoted tumor cell proliferation in vitro. Mechanistically, ATGL promoted CRC cells proliferation by blocking mTOR signaling pathway and activating autophagy process. Further, ATGL regulated autophagy process through triggering SIRT1 expression. Our results reveal that ATGL promotes colorectal cancer growth by up regulating autophagy process and SIRT1 expression.

Identification of potential diagnostic and prognostic biomarkers for breast cancer based on gene expression omnibus.

BACKGROUND: Breast cancer is regarded as a highly malignant neoplasm in the female population, posing a significant risk to women's overall well-being. The prevalence of breast cancer has been observed to rise in China, accompanied by an earlier age of onset when compared to Western countries. Breast cancer continues to be a prominent contributor to cancer-related mortality and morbidity among women, primarily due to its limited responsiveness to conventional treatment modalities. The diagnostic process is challenging due to the presence of non-specific clinical manifestations and the suboptimal precision of conventional diagnostic tests. There is a prevailing uncertainty regarding the most effective screening method and target populations, as well as the specificities and execution of screening programs. AIM: To identify diagnostic and prognostic biomarkers for breast cancer. METHODS: Overlapping differentially expressed genes were screened based on Gene Expression Omnibus (GSE36765, GSE10810, and GSE20086) and The Cancer Genome Atlas datasets. A protein-protein interaction network was applied to excavate the hub genes among these differentially expressed genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, as well as gene set enrichment analyses, were conducted to examine the functions of these genes and their potential mechanisms in the development of breast cancer. For clarification of the diagnostic and prognostic roles of these genes, Kaplan-Meier and Cox proportional hazards analyses were conducted. RESULTS: This study demonstrated that calreticulin, heat shock protein family B member 1, insulin-like growth Factor 1, interleukin-1 receptor 1, Krüppel-like factor 4, suppressor of cytokine signaling 3, and triosephosphate isomerase 1 are potential diagnostic biomarkers of breast cancer as well as potential treatment targets with clinical implications. CONCLUSION: The screening of biomarkers is of guiding significance for the diagnosis and prognosis of the diseases.

Terpenoids from Euphorbia helioscopia and Their Cytotoxic Activities against H1975 Cells.

Three previously undescribed diterpenoids, helioscopnoids A-C, and eight known compounds were isolated from the whole plants of Euphorbia helioscopia. Their structures were established by extensive analysis of spectra and data comparison with previous literatures. Among them, compound 4 was identified as 24,24-dimethoxy-25,26,27-trinoreuphan-3ß-ol with revised configurations of C-13, C-14, and C-17 (13R*, 14R*, 17R*). Cytotoxicity assays revealed that all compounds exhibited varying levels of cytotoxicity against H1975 cells, with compound 9 displaying the most potent activity, as indicated by cell viability rates of 18.13 % and 20.76 % at concentrations of 20 µM and 5 µM, respectively. This study expands the understanding of E. helioscopia terpenoids' structural diversity and biological activities, contributing to the exploration of potential therapeutic applications.

Sesquiterpenes from Carpesium faberi triggered ROS-induced apoptosis and protective autophagy in hepatocellular carcinoma cells.

Ten previously undescribed sesquiterpenes, carpespenes A-J (1-10), and eight known compounds (11-18), were isolated from the whole plants of Carpesium faberi. Their structures were established by extensive analysis of HRESIMS, NMR, and ECD spectra. Carpespene A (1) is eudesmanolide-type sesquiterpene lactone with an open five membered ring involving C-2 and C-3. Furthermore, compound 1 showed significant cytotoxic effects against four cancer cell lines with IC50 values from 8.20 to 18.45 µM, compared with the positive controls cisplatin and doxorubicin. Mechanistically, compound 1 induced apoptosis in the HepG2 cells by triggering excessive ROS accumulation. The latter however induced cytoprotective autophagy, which impaired the cytotoxicity of compound 1. Simultaneous antophagy inhibition with compound 1 treatment augmented the cytotoxic effects of the latter on HepG2 cells. Our findings further establish the structural diversity and bioactivity of sesquiterpenes, and provide an experimental basis for targeting cytoprotective autophagy as a potential chemotherapeutic strategy.

Detection of fibrotic changes in the progression of liver diseases by label-free multiphoton imaging.

Collagen fibers play an important role in the progression of liver diseases. The formation and progression of liver fibrosis is a dynamic pathological process accompanied by morphological changes in collagen fibers. In this study, we used multiphoton microscopy for label-free imaging of liver tissues, allowing direct detection of various components including collagen fibers, tumors, blood vessels, and lymphocytes. Then, we developed a deep learning classification model to automatically identify tumor regions, and the accuracy reaches 0.998. We introduced an automated image processing method to extract eight collagen morphological features from various stages of liver diseases. Statistical analysis showed significant differences between them, indicating the potential use of these quantitative features for monitoring fibrotic changes during the progression of liver diseases. Therefore, multiphoton imaging combined with automatic image processing method would hold a promising future in rapid and label-free diagnosis of liver diseases.

Corylifol A ameliorates muscle atrophy by inhibiting TAOK1/p38-MAPK/FoxO3 pathway in cancer cachexia.

BACKGROUND: Corylifol A (CYA) is one of the main active components of Psoralea corylifolia L. CYA had been reported to have ameliorating effects on dexamethasone-induced atrophy of C2C12 mouse skeletal myotubes, but its effects on cancer cachexia were unclear. Here, we checked the influence of CYA on muscle atrophy in cancer cachexia mice and tried to clarify its mechanisms. METHODS: C26 tumour-bearing mice were applied as the animal model to examine the effects of CYA in attenuating cachexia symptoms. The in vitro cell models of TNF-α-induced C2C12 myotubes or ad-mRFP-GFP-LC3B-transfected C2C12 myotubes were used to check the influence of CYA on myotube atrophy based on both ubiquitin proteasome system (UPS) and autophagy-lysosome system. The possible direct targets of CYA were searched using the biotin-streptavidin pull-down assay and then confirmed using the Microscale thermophoresis binding assay. The levels of related signal proteins in both in vitro and in vivo experiments were examined using western blotting and immunocytochemical assay. RESULTS: The administration of CYA prevented body weight loss and muscle wasting in C26 tumour-bearing mice without affecting tumour growth. At the end of the experiment, the body weight of mice treated with 30 mg/kg of CYA (23.59 ± 0.94 g) was significantly higher than that of the C26 model group (21.66 ± 0.56 g) with P < 0.05. The values of gastrocnemius muscle weight/body weight of mice treated with 15 or 30 mg/kg CYA (0.53 ± 0.02% and 0.54 ± 0.01%, respectively) were both significantly higher than that of the C26 model group (0.45 ± 0.01%) with P < 0.01. CYA decreased both UPS-mediated protein degradation and autophagy in muscle tissues of C26 tumour-bearing mice as well as in C2C12 myotubes treated with TNF-α. The thousand-and-one amino acid kinase 1 (TAOK1) was found to be the direct binding target of CYA. CYA inhibited the activation of TAOK1 and its downstream p38-MAPK pathway thus decreased the level and nuclear location of FoxO3. siRNA knockdown of TAOK1 or regulation of the p38-MAPK pathway using activator or inhibitor could affect the ameliorating effects of CYA on myotube atrophy. CONCLUSIONS: CYA ameliorates cancer cachexia muscle atrophy by decreasing both UPS degradation and autophagy. The ameliorating effects of CYA on muscle atrophy might be based on its binding with TAOK1 and inhibiting the TAOK1/p38-MAPK/FoxO3 pathway.