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The peptide hormone kisspeptin, signaling via its receptor, KISS1R, decreases hepatic steatosis and protects against metabolic dysfunction-associated steatotic liver disease (MASLD). Enhanced de novo lipogenesis (DNL) contributes to MASLD. Here, we investigated whether kisspeptin treatment in obese, diabetic mice directly attenuates DNL. DNL was assessed in kisspeptin-treated mouse livers, using a mouse model of MASLD, (DIAMOND mice), employing 2H2O-enriched water, mass spectrometry analysis, and transcriptomic profiling. Gene and protein expression were evaluated in primary hepatocytes and livers. Additionally, hepatic Kiss1r expression was increased in DIAMOND mice, following which various biochemical and metabolic assessments were employed. Metabolic tracing in kisspeptin-treated steatotic livers demonstrated a decrease in the DNL of free fatty acids (FFAs), known to be associated with diabetes, steatosis, and hepatocellular carcinoma. Transcriptomic profiling of kisspeptin-treated livers identified disruption of key metabolic pathways, the most prominent being a decrease in fatty acid metabolism, and downregulation of Cidea, a key regulator of lipid droplet formation. Kisspeptin treatment of FFA-loaded primary mouse hepatocytes significantly decreased Cidea expression. Mechanistically, we found that kisspeptin administration decreased levels of transcription factor SREBP-1c, a crucial regulator of DNL, and CIDEA. Thus, enhanced KISS1R signaling limits hepatic DNL, suggesting a crucial role in restricting MASLD.

In this paper we investigate the use of sucrose as a reducing agent for the carbothermal reduction in spent ternary cathode materials. During this process, lithium from the cathode material is converted into water-soluble Li2CO3, while the high-valent transition metals are reduced to insoluble metallic elements and oxides. The influence of various pyrolysis temperatures, sucrose dosages, and pyrolysis times on the reduction degree of high-valent metals. Furthermore, the influence of leaching conditions on lithium recovery efficiency is examined. Under the optimal conditions of a pyrolysis temperature of 650 °C, a sucrose dosage of 15 wt.%, a pyrolysis time of 30 min, a leaching solid–liquid ratio of 30 g/L, and a leaching time of 30 min, the lithium leaching rate reaches 97.9%. Characterization via XRD, XPS and SEM reveals that sucrose serves as an effective carbothermal reducing agent. It facilitates the reduction of high-valent transition metals to insoluble metallic elements and oxides while simultaneously enabling the recovery of lithium as Li2CO3. Consequently, this method achieves an efficient separation of lithium from other metallic elements. Compared to traditional recycling processes, it avoids the low lithium recovery rates often associated with subsequent separation steps.

Patients with gastric and esophageal (GE) adenocarcinoma tumors in which the oncogene ERBB2 has been amplified are routinely treated with a combination of cytotoxic chemotherapy and the ERBB2-directed antibody trastuzumab; however, the addition of trastuzumab, even when tested in a selected biomarker-positive patient population, provides only modest survival gains. To investigate the potential reasons for the modest impact of ERBB2-directed therapies, we explored the hypothesis that secondary molecular features of ERBB2-amplified GE adenocarcinomas attenuate the impact of ERBB2 blockade. We analyzed genomic profiles of ERBB2-amplified GE adenocarcinomas and determined that the majority of ERBB2-amplified tumors harbor secondary oncogenic alterations that have the potential to be therapeutically targeted. These secondary events spanned genes involved in cell-cycle regulation as well as phosphatidylinositol-3 kinase and receptor tyrosine kinase signaling. Using ERBB2-amplified cell lines, we demonstrated that secondary oncogenic events could confer resistance to ERBB2-directed therapies. Moreover, this resistance could be overcome by targeting the secondary oncogene in conjunction with ERBB2-directed therapy. EGFR is commonly coamplified with ERBB2, and in the setting of ERBB2 amplification, higher EGFR expression appears to mark tumors with greater sensitivity to dual EGFR/ERBB2 kinase inhibitors. These data suggest that combination inhibitor strategies, guided by secondary events in ERBB2-amplified GE adenocarcinomas, should be evaluated in clinical trials.

Background Programmed death ligand 1 (PD-L1) is a ligand for the inhibitory programmed cell death protein 1 (PD-1), which are targeted by several anti-PD-1 and PD-L1 drugs for a variety of human cancers. However, only a few studies have evaluated PD-L1 expression in esophageal squamous cell carcinoma (ESCC) with a large Chinese cohort. Our present study is to evaluate the association of PD-L1 expression with clinicopathological features on ESCC. Methods Using tissue microarray and immunohistochemistry, PD-L1 expression on tumor cells and tumor-infiltrating immune cells was studied in 378 advanced ESCC patients without neoadjuvant chemoradiotherapy. Its correlation with clinicopathological parameters was analyzed. Results PD-L1 was expressed on 29.9% (113/378) ESCC tumor cells and 40.2% (152/378) tumor-infiltrating immune cells. PD-L1 expression in tumor cells was significantly correlated with age, degree of differentiation, T stage, N stage and metachronous hematogenous metastasis, and PD-L1 expression in tumor-infiltrating immune cells was significantly associated with N stage ( P  < 0.05). Patients with PD-L1 expression in tumor cells had poor disease-free survival (Hazard ratio [HR] = 1.436, P  = 0.009). There was a positive association between tumor cells and tumor-infiltrating immune cells for PD-L1 expression ( r  = 0.16, P  = 0.002). However, PD-L1 expression in tumor-infiltrating immune cells was not significantly correlated with disease-free survival and overall survival. Conclusions PD-L1 expression in tumor cells and tumor infiltrating immune cells is not only an indicator for immunotherapy, but also significantly related with age, differentiation, stage, metastasis and disease free survival.

Background The BRAFV600E mutation is valuable for the diagnosis, prognosis, and therapy of papillary thyroid cancer (PTC). However, studies related to this mutation have involved only a small number of patients. Therefore, we performed a large‐scale analysis from a single institute to evaluate the accuracy of combined fine‐needle aspiration (FNA) and BRAFV600E mutation tests for PTC diagnosis. Methods A total of 4600 patients with thyroid nodules who underwent both FNA cytology and BRAFV600E mutation analysis on FNA specimens were enrolled. The association between the BRAFV600E mutation and clinicopathological features was analyzed. A separate analysis was performed for the 311 patients who underwent repeated FNA for comparison of cytological evaluation and BRAFV600E mutation results. The diagnostic efficacy of the BRAFV600E mutation test and cytologic diagnoses was evaluated for 516 patients who underwent preoperative FNA tests in comparison with conclusive postoperative histopathologic results. Results The cytology results of all 4600 FNA samples were categorized according to The Bethesda System for Reporting Thyroid Cytology (TBSRTC) stages I–VI, which accounted for 11.76%, 60.02%, 6.46%, 3.61%, 6.71%, and 11.43% of the samples, respectively. The BRAFV600E mutation was detected in 762 (16.57%) FNA samples, with rates of 1.48%, 0.87%, 20.20%, 3.01%, 66.02%, and 87.81% for TBSRTC I–VI lesions, respectively. Among the 311 repeat FNA cases, 81.0% of the BRAFV600E‐positive and 4.3% of the BRAFV600E‐negative specimens with an initial indication of cytological non‐malignancy were ultimately diagnosed as malignant by repeat FNA (p < 0.001). Among the 516 patients who underwent thyroidectomy, the sensitivity and specificity of the BRAFV600E mutation test alone for PTC diagnosis were 76.71% and 100.0%, respectively, which increased to 96.62% and 88.03%, respectively, when combining the BRAFV600E mutation test with cytology. BRAFV600E mutation was significantly associated with lymph node metastasis (p < 0.001), but not with age, gender, or tumor size. Conclusions The BRAFV600E mutation test in FNA samples has potential to reduce false negatives in PTC diagnosis, and therefore plays an important role in the diagnosis of thyroid nodules, especially those with an indeterminate or nondiagnostic cytology, which should be considered for repeat FNA. BRAFV600E mutation test in fine‐needle aspiration (FNA) will reduce the false negative. BRAF test on FNA samples plays an important role in diagnosis of thyroid nodules, especially indeterminate or nondiagnostic cytology initially which is considered to receive repeat FNA.

In this study, a novel rapid immunochromatographic (IC) test for African swine fever virus (ASFV) antibodies is presented. An immunochromatographic test (IC) is a detection technique that combines membrane chromatography with immunolabeling. This approach saves time for antibody preparation, resulting in a shorter production cycle. p54 is an important structural protein of African swine fever, and an ideal protein for serotype diagnosis. Gold nanoparticles are attached to the ASFV p54-Fc fusion protein, and the ASFV-specific antigen p54 and Staphylococcus aureus protein A (SPA) are labeled on a nitrocellulose membrane, at positions T and C, respectively. We developed a SPA double sandwich IC test strip, and assessed its feasibility using ASFV p54 and p54-Fc fusion proteins as antigens. ASFV p54 and p54-Fc fusion proteins were expressed and purified. A sandwich cross-flow detection method for p54, which is the primary structural protein of ASFV, was established, using colloidal gold conjugation. Our method can detect ASFV antibodies in field serum samples in about 15 min using a portable colloidal gold detector, demonstrating high specificity and sensitivity (1:320), and the coincidence rate was 98% using a commercial ELISA kit. The dilution of the serum sample can be determined by substituting the absorbance (T-line) interpreted by portable devices into the calibration curve function formula of an African swine fever virus standard serum. In summary, our method is rapid, cost-effective, precise, and highly selective. Additionally, it introduces a new approach for constructing IC test strips using SPA protein without antibody preparation, making it a reliable on-site antibody test for ASFV.

Beijing, the capital of China, is experiencing a serious lack of water, which is becoming a main factor in the restriction of the development of the social economy. Due to the low economic efficiency and high consumption proportion of agricultural water use, the relationship between economic growth and agricultural water use is worth investigating. The “decoupling” index is becoming increasingly popular for identifying the degree of non-synchronous variation between resource consumption and economic growth. However, few studies address the decoupling between the crop water consumption and agricultural economic growth. This paper involves the water footprint (WF) to assess the water consumption in the crop production process. After an evaluation of the crop WF in Beijing, this paper applies the decoupling indicators to examine the occurrence of non-synchronous variation between the agricultural gross domestic product (GDP) and crop WF in Beijing from 1981 to 2013. The results show that the WF of crop production in 2013 reduced by 62.1% compared to that in 1980 — in total, 1.81 × 109 m 3 . According to the decoupling states, the entire study period is divided into three periods. From 1981 to 2013, the decoupling states represented seventy-five percent of the years from 1981 to 1992 (Period I) with a moderate decoupling degree, more than ninety percent from 1993 to 2003 (Period II) with a very strong decoupling degree and moved from non-decoupling to strong decoupling from 2004 to 2013 (Period III). Adjusting plantation structure, technology innovation and raising awareness of water-saving, may promote the decoupling degree between WF and agricultural GDP in Beijing.

The peptide hormone kisspeptin attenuates liver steatosis, metabolic dysfunction-associated steatohepatitis (MASH), and fibrosis in mouse models by signaling via the kisspeptin 1 receptor (KISS1R). However, whether kisspeptin impacts fibrogenesis in the human liver is not known. We investigated the impact of a potent kisspeptin analog (KPA) on fibrogenesis using human precision-cut liver slices (hPCLS) from fibrotic livers from male patients, in human hepatic stellate cells (HSCs), LX-2, and in primary mouse HSCs. In hPCLS, 48 h and 72 h of KPA (3 nM, 100 nM) treatment decreased collagen secretion and lowered the expression of fibrogenic and inflammatory markers. Immunohistochemical studies revealed that KISS1R is expressed and localized to HSCs in MASH/fibrotic livers. In HSCs, KPA treatment reduced transforming growth factor b (TGFβ)-the induced expression of fibrogenic and inflammatory markers, in addition to decreasing TGFβ-induced collagen secretion, cell migration, proliferation, and colony formation. Mechanistically, KISS1R signaling downregulated TGFβ signaling by decreasing SMAD2/3 phosphorylation via the activation of protein phosphatases, PP2A, which dephosphorylates SMAD 2/3. This study revealed for the first time that kisspeptin reverses human hepatic fibrogenesis, thus identifying it as a new therapeutic target to treat hepatic fibrosis.

The HER2 oncogene was recently reported to be amplified and overexpressed in esophageal adenocarcinoma. However, the relationship of HER2 amplification in esophageal adenocarcinoma with prognosis has not been well defined. The scoring systems for clinically evaluating HER2 in esophageal adenocarcinoma are not established. The aims of the study were to establish a HER2 scoring system and comprehensively investigate HER2 amplification and overexpression in esophageal adenocarcinoma and its precursor lesion. Using a tissue microarray, containing 116 cases of esophageal adenocarcinoma, 34 cases of Barrett's esophagus, 18 cases of low-grade dysplasia and 15 cases of high-grade dysplasia, HER2 amplification and overexpression were analyzed by HercepTest and chromogenic in situ hybridization methods. The amplification frequency in an independent series of 116 esophageal adenocarcinoma samples was also analyzed using Affymetrix SNP 6.0 microarrays. In our studies, we have found that HER2 amplification does not associate with poor prognosis in total 232 esophageal adenocarcinoma patients by chromogenic in situ hybridization and high-density microarrays. We further confirm the similar frequency of HER2 amplification by chromogenic in situ hybridization (18%; 21 out of 116) and SNP 6.0 microarrays (16%, 19 out of 116) in esophageal adenocarcinoma. HER2 protein overexpression was observed in 12% (14 out of 116) of esophageal adenocarcinoma and 7% (1 out of 15) of high-grade dysplasia. No HER2 amplification or overexpression was identified in Barrett's esophagus or low-grade dysplasia. All HER2 protein overexpression cases showed HER2 gene amplification. Gene amplification was found to be more frequent by chromogenic in situ hybridization than protein overexpression in esophageal adenocarcinoma (18 vs 12%). A modified two-step model for esophageal adenocarcinoma HER2 testing is recommended for clinical esophageal adenocarcinoma HER2 trial.

Background The presence of dilated intercellular spaces in the stratified squamous lining of the esophagus is the pathognomonic feature of reflux esophagitis secondary to gastroesophageal reflux disease (GERD). In addition to stomach acid, bile salts are major constituents of gastroesophageal refluxate. The aim of our study was to determine the effect of bile salts cocktail at different pHs on epithelial junctions in an in vitro transwell model of stratified esophageal squamous epithelium. Discussion Human telomerase reverse transcriptase (hTERT) immortalized primary esophageal EPC1 cells were grown on polyester transwell surfaces in calcium-enriched media. The cells exhibited gradual stratification into an 11-layered squamous epithelium over 7 days, together with epithelial barrier function as indicated by increased transepithelial electrical resistance (TEER). This stratified epithelium demonstrated well-formed tight junctions, adherens junctions, and desmosomes as visualized by immunofluorescence and electron microscopy. When exposed to short pulses of bile salts at pH 5, but not either condition alone, there was loss of stratification and decrease in TEER, concomitant with disruption of adherens junctions, tight junctions, and desmosomes, leading to the appearance of dilated intercellular spaces. At the cellular level, bile salts at pH 5 activated the Wnt pathway (indicated by increased β-catenin Ser552 phosphorylation). Conclusion In conclusion, in our in vitro transwell model bile salts at pH 5, but not bile salts or media at pH 5 alone, modulate Wnt signaling, disrupt different junctional complexes, and cause increased permeability of stratified squamous esophageal epithelium. These changes approximate the appearance of dilated intercellular space similar to that found in GERD patients.