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Amino acids are the building blocks of protein synthesis. They are structural elements and energy sources of cells necessary for normal cell growth, differentiation and function. Amino acid metabolism disorders have been linked with a number of pathological conditions, including metabolic diseases, cardiovascular diseases, immune diseases, and cancer. In the case of tumors, alterations in amino acid metabolism can be used not only as clinical indicators of cancer progression but also as therapeutic strategies. Since the growth and development of tumors depend on the intake of foreign amino acids, more and more studies have targeted the metabolism of tumor-related amino acids to selectively kill tumor cells. Furthermore, immune-related studies have confirmed that amino acid metabolism regulates the function of effector T cells and regulatory T cells, affecting the function of immune cells. Therefore, studying amino acid metabolism associated with disease and identifying targets in amino acid metabolic pathways may be helpful for disease treatment. This article mainly focuses on the research of amino acid metabolism in tumor-oriented diseases, and reviews the research and clinical research progress of metabolic diseases, cardiovascular diseases and immune-related diseases related to amino acid metabolism, in order to provide theoretical basis for targeted therapy of amino acid metabolism.

Cornus officinalis Sieb. et Zucc. is part of the genus Cornus of the family Cornaceae . Ripening and dry fruits ( Corni Fructus ) are recognized as an essential herb medicine in the traditional Chinese medicine (TCM) and have been widely used for over 2000 years. This review provides a comprehensive summary of Corni Fructus (CF), including the botany, phytochemistry, traditional use, and current pharmacological activities. According to the basic theory of TCM, CF usually participates in various Chinese medicinal formulae to exert the essential roles in replenishing liver and kidney, arresting seminal emission and sweat. Based on modern pharmacological studies, about 90 compounds have been isolated and identified from CF. In vivo and in vitro experimental studies indicate that CF exhibits extensive pharmacological activities including hypoglycemic, antioxidant, anti-inflammatory, anticancer, neuroprotective, hepatoprotective, and nephroprotective activities. However, only about 18% of chemical constituents in CF were tested. It means the potential pharmacological activities and clinical values of CF need to be further investigated.

Inspired by the recent discovery of the doubly charmed tetraquark state Tcc+ by the LHCb Collaboration, we perform a systematic study of masses and strong decays of open charm hexaquark states Σc(∗)Σc(∗). Taking into account heavy quark spin symmetry breaking, we predict several bound states of isospin I=0, I=1, and I=2 in the one boson exchange model. Moreover, we adopt the effective Lagrangian approach to estimate the decay widths of Σc(∗)Σc(∗)→ΛcΛc and their relevant ratios via the triangle diagram mechanism, which range from a few MeV to a few tens of MeV. We strongly recommend future experimental searches for the Σc(∗)Σc(∗) hexaquark states in the ΛcΛc invariant mass distributions.

Objectives Thrombospondin 1 (THBS1) is known to play a key role in tumor metastasis, and aberrant DNA methylation is one of the mechanisms regulating THBS1. The present study investigated whether methylated THBS1 in circulating cell‐free DNA from preoperative peritoneal lavage fluid (PPLF) and peripheral blood could be used as a potential biomarker for predicting peritoneal dissemination in gastric cancer (GC) patients. Methods The status of THBS1 methylation was detected by quantitative methylation‐specific PCR (MSP) in tumor tissues, paired PPLF, and serum from 92 GC patients. The correlation between methylated THBS1 levels and peritoneal dissemination of GC was studied, and its diagnostic value for predicting peritoneal dissemination was clarified by the receiver operating characteristic (ROC) curve. Results Aberrant THBS1 methylation in tumor tissues was significantly higher than that in paracancerous normal tissues (p < 0.0001). No THBS1 methylation was found in 40 healthy controls, and partial methylation was detected in 3 of 48 patients with chronic non‐atrophic gastritis. The frequency of THBS1 methylation in pairing PPLF and serum from 92 GC patients was 52.2% (48/92) and 58.7% (54/92), respectively. The results of methylated THBS1 in pairing PPLF and serum were similar to those of tumor tissues. Aberrant THBS1 methylation in tumor tissues and pairing PPLF or serum was closely related to peritoneal dissemination, tumor progression, and poor prognosis (all p < 0.0001). Conclusion Circulating methylated THBS1 DNAs in PPLF/serum may predict peritoneal dissemination, a potential poor prognostic factor for GC patients. Postoperative recurrence of gastric cancer usually occurs in the peritoneum, and peritoneal dissemination and recurrence are the main causes of poor prognosis. Therefore, it is very necessary to find a biomarker that can predict peritoneal dissemination of gastric cancer cells. Here, we found that THBS1 methylation levels in preoperative serum or peritoneal fluid can accurately predict peritoneal dissemination and suggest a poor prognosis in patients with gastric cancer.

Background Prediction of lymph node metastasis (LNM) is critical for individualized management of papillary thyroid carcinoma (PTC) patients to avoid unnecessary overtreatment as well as undesired under-treatment. Artificial intelligence (AI) trained by thyroid ultrasound (US) may improve prediction performance. Methods From September 2017 to December 2018, patients with suspicious PTC from the first medical center of the Chinese PLA general hospital were retrospectively enrolled to pre-train the multi-scale, multi-frame, and dual-direction deep learning (MMD-DL) model. From January 2019 to July 2021, PTC patients from four different centers were prospectively enrolled to fine-tune and independently validate MMD-DL. Its diagnostic performance and auxiliary effect on radiologists were analyzed in terms of receiver operating characteristic (ROC) curves, areas under the ROC curve (AUC), accuracy, sensitivity, and specificity. Results In total, 488 PTC patients were enrolled in the pre-training cohort, and 218 PTC patients were included for model fine-tuning ( n  = 109), internal test ( n  = 39), and external validation ( n  = 70). Diagnostic performances of MMD-DL achieved AUCs of 0.85 (95% CI: 0.73, 0.97) and 0.81 (95% CI: 0.73, 0.89) in the test and validation cohorts, respectively, and US radiologists significantly improved their average diagnostic accuracy (57% vs. 60%, P  = 0.001) and sensitivity (62% vs. 65%, P  < 0.001) by using the AI model for assistance. Conclusions The AI model using US videos can provide accurate and reproducible prediction of cervical lymph node metastasis in papillary thyroid carcinoma patients preoperatively, and it can be used as an effective assisting tool to improve diagnostic performance of US radiologists. Trial registration We registered on the Chinese Clinical Trial Registry website with the number ChiCTR1900025592.

The three pentaquark states, Pc(4312), Pc(4440) and Pc(4457), discovered by the LHCb Collaboration in 2019, are often interpreted as D¯(∗)Σc molecules. Together with their four D¯(∗)Σc∗ partners dictated by heavy quark spin symmetry they represent a complete multiplet of hadronic molecules of D¯(∗)Σc(∗). The pentaquark states were observed in the J/ψp invariant mass distributions of the Λb→J/ψpK decay. It is widely recognized that to understand their nature, other discovery channels play an important role. In this work, we investigate two three-body decay modes of the D¯(∗)Σc(∗) molecules. The tree-level modes proceed via off-shell Σc(∗) baryons, D¯(∗)Σc(∗)→D¯(∗)Σc(∗)→Λcπ→D¯(∗)Λcπ, while the triangle-loop modes proceed through D¯∗Σc(∗)→J/ψNπ, ηcNπ via D¯Σc(∗) rescattering to J/ψN and ηcN. Our results indicate that the decay widths of the Pc(4457) and D¯(∗)Σc∗ states into D¯(∗)Λcπ are several MeV, as a result can be observed in the upcoming Run 3 and Run 4 of LHC. The partial decay widths into D¯(∗)Λcπ of the Pc(4312) and Pc(4440) states range from tens to hundreds of keV. In addition, the partial decay widths of D¯∗Σc molecules into J/ψNπ and ηcNπ are several keV and tens of keV, respectively, and the partial decay widths of D¯∗Σc∗ molecules into J/ψNπ vary from several keV to tens of keV. In particular, we show that the spin-5/2 D¯∗Σc∗ state can be searched for in the J/ψNπ and D¯∗Λcπ invariant mass distributions, while the latter one is more favorable. These three-body decay modes of the pentaquark states are of great value to further observations of the pentaquark states and to a better understanding of their nature.

Progesterone and AdipoQ Receptor 3 (PAQR3) is a member of the AdipoQ receptor. Our previous studies have found that PAQR3 plays a role as a candidate inhibitor in cardiac adenocarcinoma, breast cancer, gastric cancer and colorectal cancer, but the systematic analysis of PAQR3 in tumors is currently lacking. The objective of this study was to investigate the prognostic and therapeutic value of PAQR3 in 31 tumors. Through the analysis of TCGA, UALCAN, GEO, GEPIA2, TIMER, Kaplan–Meier plotter, TISIDB and other databases, it was found that the expression level of PAQR3 changed significantly in different tumor types, and the expression level of Neuroblastoma was very high. And the level of Prostate adenocarcinoma is low. In addition, the expression level of PAQR3 in Cholangiocarcinoma, Esophageal carcinoma, Head and neck squamous carcinoma, Liver Hepatocellular Carcinoma, Lung Adenocarcinoma and Lung squamous cell carcinoma was significantly higher than that in normal tissues. However, the expression level of PAQR3 in Breast Cancer, Kidney Renal Clear Cell Carcinoma, Kidney renal papillary cell carcinoma, Prostate Adenocarcinoma, Rectum Adenocarcinoma, Thyroid Cancer and Uterine Corpus Endometrial Carcinoma was lower than that in normal tissues. Subsequently, we explored the value of PAQR3 as a prognostic indicator of cancer. In Acute Myeloid Leukemia, Lower-grade Glioma and Glioblastoma, Pediatric Low-grade Gliomas, Kidney Chromophobe, and Thyroid Cancer, PAQR3 expression was positively correlated with OS and DSS, while in Rectum Adenocarcinoma, PAQR3 expression was negatively correlated with OS. PAQR3 high expression group Lower-grade Glioma and Glioblastoma, Pediatric Low-grade Gliomas, Uveal Melanoma, Kidney Chromophobe and DFI were positively correlated. PAQR3 can be used as a risk factor for the prognosis of multiple tumors. Then, we discussed the correlation between PAQR3 and immunology, and found that PAQR3 has a wide range of mutations in various tumor types, the most common mutation type is missense mutation, and common mutation types also include amplification, depth deletion, splicing, truncation and structural variation. Among the tumor samples with PAQR3 alterations, mutation occurred in all tumor samples except prostate adenocarcinoma and adrenal cortical carcinoma, head and neck squamous cell carcinoma, brain low-grade glioma, and kidney clear cell carcinoma, while esophageal adenocarcinoma had the highest total alteration frequency. PAQR3 was strongly associated with CNV in 18 tumors, particularly in Ovarian cancer, Lung squamous cell carcinoma, and Adenoid cystic carcinoma. On the other hand, PAQR3 has a higher SNV frequency in Uterine Corpus Endometrial Carcinoma, Skin Cutaneous Melanoma and Lung Adenocarcinoma, among which Uterine Corpus Endometrial Carcinoma has the highest SNV frequency. These results showed that PAQR3 expression levels were significantly correlated with tumor mutation load, microsatellite instability, neoantigens, and purity. In summary, PAQR3 can affect the tumor microenvironment and has potential for chemotherapy. Finally, we investigated the role of PAQR3 in tumor resistance and found that the expression of PAQR3 affects the efficacy of multiple chemotherapy drugs. Based on these studies, we found that PAQR3 plays an important role in cancer and has potential in tumor diagnosis and prognosis.

Cellulose is often described as a mixture of crystalline and amorphous material. A large part of the general understanding of the chemical, biochemical and physical properties of cellulosic materials is thought to depend on the consequences of the ratio of these components. For example, amorphous materials are said to be more reactive and have less tensile strength but comprehensive understanding and definitive analysis remain elusive. Ball milling has been used for decades to increase the ratio of amorphous material. The present work used 13 techniques to follow the changes in cotton fibers (nearly pure cellulose) after ball milling for 15, 45 and 120 min. X-ray diffraction results were analyzed with the Rietveld method; DNP (dynamic nuclear polarization) natural abundance 2D NMR studies in the next paper in this issue assisted with the interpretation of the 1D analyses in the present work. A conventional NMR model’s paracrystalline and inaccessible crystallite surfaces were not needed in the model used for the DNP studies. Sum frequency generation (SFG) spectroscopy also showed profound changes as the cellulose was decrystallized. Optical microscopy and field emission-scanning electron microscopy results showed the changes in particle size; molecular weight and carbonyl group analyses by gel permeation chromatography confirmed chemical changes. Specific surface areas and pore sizes increased. Fourier transform infrared (FTIR) and Raman spectroscopy also indicated progressive changes; some proposed indicators of crystallinity for FTIR were not in good agreement with our results. Thermogravimetric analysis results indicated progressive increase in initial moisture content and some loss in stability. Although understanding of structural changes as cellulose is amorphized by ball milling is increased by this work, continued effort is needed to improve agreement between the synchrotron and laboratory X-ray methods used herein and to provide physical interpretation of the SFG results.

Objectives To investigate the function of PAQR3 in gastric cardia adenocarcinoma (GCA) and understand the possible mechanism of PAQR3 in regulating epithelial–mesenchymal transition (EMT). Methods We detected PAQR3 protein in 146 GCA tissues and paired normal adjacent tissues (PNTs) specimens using immunohistochemical analysis, and explored its clinical significance. The expression levels of PAQR3 protein in 20 GCA tissues, their paired PNTs, HGC27, SGC7901, and GES‐1 cells were analyzed by Western blot. Wild‐type PAQR3 was overexpressed in HGC27 cells. The effects of PAQR3 overexpression on the function of HGC27 cells and its underlying mechanisms were then analyzed through a series of cell and molecular biology experiments. Results PAQR3 was significantly down‐regulated in GCA tissues when compared with paired PNTs (p < 0.0001). The expression level of PAQR3 in GCA tissues was significantly negatively correlated with Helicobacter pylori infection (p = 0.000), venous invasion (p = 0.000), invasion depth (p = 0.000), lymph node metastasis (p = 0.022), tumor stage (p = 0.000), and patient survival (p = 0.009). Downregulation of PAQR3 was highly correlated with increased EMT signature and activated TGF‐β/Smad pathway in GCA tissues. Overexpression of PAQR3 in HGC27 cells negatively regulates its cellular functions, such as cell proliferation and migration, and suppresses EMT. Mechanistically, overexpression of PAQR3 significantly down‐regulates the protein expression levels of TGF‐1, p‐Smad2, and p‐Smad3 in HGC27 cells. Conclusion PAQR3 was significantly down‐regulated in GCA tissues, HGC27, and SGC7901 cells. PAQR3 significantly inhibits the proliferation, migration, and invasion of HGC27 cells. Mechanistically, PAQR3 can inhibit the EMT process in HGC27 cells by regulating TGF‐β/Smad signaling pathway. PAQR3 as a novel tumor suppressor gene can inhibit multiple tumorigenesis and development by regulating multiple signaling pathways, but whether PAQR3 can regulate TGF‐β signaling to influence the progression of GCA is unknown. In this study, we found that PAQR3 expression was lower in GCA tissues, HGC27, and SGC7901 cells. PAQR3 can inhibit the proliferation, migration, and invasion of HGC27 cells. Mechanistically, PAQR3 was able to inhibit the epithelial–mesenchymal transition (EMT) process in HGC27 cells through regulating TGF‐β/Smad signaling.

Background Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined. Methods We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP. Results Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity. Conclusions We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment.