ObjectiveBola-like short peptides exhibit novel self-assembly properties due to the formation of peptide dimers via hydrogen bonding interactions between their C-terminals. In this configuration, hydrophilic amino acids are distributed at both terminals, making these peptides behave similarly to Bola peptides. The electrostatic repulsive interactions arising from the hydrophilic amino acids at each terminal can be neutralized, thereby greatly promoting the lateral association of β-sheets. Consequently, assemblies with significantly larger widths are typically the dominant nanostructures for Bola-like peptides. To investigate the effect of hydrophilic amino acids on the self-assembly behavior of Bola-like peptides, the peptides Ac-RI₃-CONH₂ and Ac-HI₃-CONH₂ were designed and synthesized using the Bola-like peptide Ac-KI₃-CONH₂ as a template. Their self-assembly behavior was systematically examined. MethodsAtomic force microscopy (AFM) and transmission electron microscopy (TEM) were employed to characterize the morphology and size of the assemblies. The secondary structures of the assemblies were analyzed using circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy. Small-angle neutron scattering (SANS) was used to obtain detailed structural information at a short-length scale. Based on these experimental results, the effects of hydrophilic amino acids on the self-assembly behavior of Bola-like short peptides were systematically analyzed, and the underlying formation mechanism was explored. ResultsThe aggregation process primarily involved three steps. First, peptide dimers were formed through hydrogen bonding interactions between their C-terminals. Within these dimers, the hydrophilic amino acids K, R, and H were positioned at both terminals, enabling the peptides to self-assemble in a manner similar to Bola peptides. Next, β-sheets were formed via hydrogen bonding interactions along the peptide backbone. Finally, self-assemblies were generated through the lateral association of β-sheets. The results demonstrated that both Ac-KI₃-CONH₂ and Ac-RI₃-CONH₂ could self-assemble into double-layer nanotubes with diameters of approximately 200 nm. These nanotubes were formed by the edge fusion of helical ribbons, which initially emerged from twisted ribbons. Notably, the primary assemblies of these peptides exhibited opposite chirality: nanofibers formed by Ac-KI₃-CONH₂ displayed left-handed chirality, whereas those formed by Ac-RI₃-CONH₂ exhibited right-handed chirality. This reversal in torsional direction was primarily attributed to the different abilities of K and R to form hydrogen bonds with water. In contrast, Ac-HI₃-CONH₂ formed narrower twisted ribbons with a significantly reduced width of approximately 30 nm, which was attributed to the strong steric hindrance caused by the imidazole rings. The multilayer height of these ribbons was mainly due to the unique structure of the imidazole rings, which can function as both hydrogen bond donors and acceptors, thereby promoting aggregate growth in the vertical direction. ConclusionThe final morphology of the self-assemblies resulted from a delicate balance of various non-covalent interactions. By altering the types of hydrophilic amino acid residues in Bola-like short peptides, the relative strength of non-covalent interactions that drive assembly formation can be effectively regulated, allowing precise control over the morphology and chirality of the assemblies. This study provides a simple and effective approach for constructing diverse self-assemblies and lays a theoretical foundation for the development of functional biomaterials.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Objective To investigate the correlation between serum leptin level and body mass index(BMI)in in-fants with cyanosis congenital heart disease,and the relationship between leptin and Ob gene receptor(Ob-R)and hypoxia-inducible factor 1α(HIF-1α)in myocardium.Methods A total of 52 children under 6 months of age with congenital heart disease who underwent surgical treatment in the Department of Congenital Heart Surgery,Fuwai Hospital from January 2019 to October 2020 were included in this study.According to the arterial partial pressure of oxygen(PaO2)of 90 mmHg,they were divided into cyanotic group(n=30)and acyanotic group(n=22).Their height and weight were collected to calculate BMI.The serum leptin level was measured by ELISA.The ex-pressions of HIF-1α and Ob-R in myocardial tissue were detected by RT-PCR and Western blot.In animal mod-el,SD rats were divided into normoxia group and hypoxia intervention group,which were subjected to continuous hypoxia(10％ O2)for 4 weeks.The hypoxia intervention group received intraperitoneal injection of HIF-1α in-hibitor digoxin(2 mg/kg)daily from the 14 th to 21st day of hypoxia,respectively.The body weight of rats was recorded,and the expressions of HIF-1α and Ob-R were detected by RT-qPCR and Western blot.Results Com-pared with the acyanosis group,the cyanosis group had a significantly lower BMI(P<0.05)and a lower leptin/BMI ratio(leptin/BMI)(P<0.05).Spearman correlation analysis confirmed that serum leptin in the circulatory system was positively correlated with BMI(P<0.05).In the cyanosis group,the expression of Ob-R increased with the upregulation of HIF-1α,showing a positive correlation.In animal model,with the down-regulation of HIF-1α expression in digoxin injection,the Ob-R level was significantly lower than that in the control group(P<0.05),the trend of weight loss was significantly inhibited(P<0.05).The right ventricular hypertrophy in-dex was significantly lower than that in the control group(P<0.05).Conclusions HIF-1α regulates the expres-sion of Ob-R in myocardial tissue,and the mechanism of its association with leptin and Ob-R may help to find new therapeutic target for improving the prognosis of infants with congenital heart disease.

Objective To evaluate the safety and efficacy of splenectomy with distal pancreatectomy during cytoreductive surgery in epithelial ovarian cancer(EOC).Methods A total of 17 patients from Zhongshan Hospital,Fudan University and the First Affiliated Hospital of University of Science and Technology of China(Anhui Provincial Hospital)received splenectomy with distal pancreatectomy during cytoreductive surgery in EOC were recruited.Their clinicopathological characteristics,postoperative complications and survival situation were retrospective analyzed.Results Of the 17 patients,there were 13 primary cases and 4 recurrent cases.Eleven cases(64.7%)had preoperative imaging finding with metastatic lesions in the splenic hilum,among whom 6 cases had distal pancreas metastasis during the operation.The drainage was placed in the splenic fossa for the measurement of amylase levels in drain fluid and was removed after 8(3-12)days.There were 4 patients had postoperative pancreatic fistula(POPF)of grade A,3 patients had POPF of grade B and no POPF of grade C occurred.The 2 patients with POPF of grade B improved after percutaneous drainage,and the rest recovered with somatostatin,antibiotic drugs and medicines without perioperative mortality.The interval between surgery to chemotherapy was 17.5(13-37)days.The median follow-up time was 14(4-64)months and the median progression-free survival was 10(5-32)months.Conclusion Splenectomy with distal pancreatectomy as part of cytoreduction surgery in EOC is needed for optimal resection,and the complication of pancreatic fistula could be managed conservatively.

OBJECTIVE: To investigate a new noninvasive diagnostic model for nonalcoholic fatty liver disease (NAFLD) based on features of tongue images. METHODS: Healthy controls and volunteers confirmed to have NAFLD by liver ultrasound were recruited from China-Japan Friendship Hospital between September 2018 and May 2019, then the anthropometric indexes and sampled tongue images were measured. The tongue images were labeled by features, based on a brief protocol, without knowing any other clinical data, after a series of corrections and data cleaning. The algorithm was trained on images using labels and several anthropometric indexes for inputs, utilizing machine learning technology. Finally, a logistic regression algorithm and a decision tree model were constructed as 2 diagnostic models for NAFLD. RESULTS: A total of 720 subjects were enrolled in this study, including 432 patients with NAFLD and 288 healthy volunteers. Of them, 482 were randomly allocated into the training set and 238 into the validation set. The diagnostic model based on logistic regression exhibited excellent performance: in validation set, it achieved an accuracy of 86.98%, sensitivity of 91.43%, and specificity of 80.61%; with an area under the curve (AUC) of 0.93 [95% confidence interval (CI) 0.68-0.98]. The decision tree model achieved an accuracy of 81.09%, sensitivity of 91.43%, and specificity of 66.33%; with an AUC of 0.89 (95% CI 0.66-0.92) in validation set. CONCLUSIONS The features of tongue images were associated with NAFLD. Both the 2 diagnostic models, which would be convenient, noninvasive, lightweight, rapid, and inexpensive technical references for early screening, can accurately distinguish NAFLD and are worth further study.
Humans ; Non-alcoholic Fatty Liver Disease/diagnostic imaging* ; Ultrasonography ; Anthropometry ; Algorithms ; China

Objective To construct a risk prediction model for liver cancer in patients with chronic hepatitis C based on seven different machine learning algorithms and select the optimal model. Methods A total of 236 patients with chronic hepatitis C were selected as the research subjects. Patients were divided into a case group and a control group according to whether liver cancer occurs. Prediction models were constructed based on seven machine learning algorithms including classification and regression tree, random forest, gradient boosting decision tree, extreme gradient boosting (XGBoost), logistic regression, K-near neighbor, and support vector machine. The Shapley additive explanations (SHAP) algorithm was used to interpret the best prediction model. Results Among the seven models, the XGBoost model had the best comprehensive prediction performance (accuracy of 0.933, sensitivity of 0.775, specificity of 0.960, area under the ROC curve of 0.956, F1 score of 0.764). The SHAP algorithm suggested that AFP, age, AST, diabetes, BMI, PLT, ALT, liver cysts, FIB-4, and gender contributed to the model decision and are the risk factors for liver cancer in patients with chronic hepatitis C. Conclusion This study develops an interpretable machine learning model based on the XGBoost algorithm, which has a good reference value for individualized monitoring of liver cancer in patients with chronic hepatitis C.

OBJECTIVE To evaluate the quality and existing problems of Compound Paracetamol and Chlorphenamine Tablets for Infant. METHODS Using legal standards to inspect sampled samples, and several analytical methods were subsequently established or improved for the exploratory research on related substances, assay, dissolution, subdivision characteristics of scored tablets, and genotoxic impurities. RESULTS All samples met the regulatory specification, and the pass rate was 100%. However, the control for related substances was lacking, and the method for assay and content uniformity was defective. The exploratory studies showed that the assay and content uniformity met the requirements, and the risk of related substances and genotoxic impurities was acceptable. As a divisible tablet, the subdivision characteristics could not meet the requirements of the scored tablet, and the dissolution performance of some enterprise samples could not meet the requirements of similar products in foreign pharmacopoeias. CONCLUSION The overall quality of this product is adequate. However, due to the early time on the market, some quality attributes no longer meet the requirements of current regulations or relevant guidelines. The manufacturers should further optimize the prescription and production process, referring to foreign similar products. The current specification needs to be revised and improved.

【Objective】 To explore the expression of USP9X in platelets and its effect on platelet function. 【Methods】 The expression of USP9X in human and mouse was evaluated by PCR and Western blot. Platelets from young and old mice were separated and prepared, and the expression of USP9X was detected. USP9X inhibitos were used to assess the regulation of USP9X in platelet function, including aggregation, ATP release and spreading. Platelet lysates were collected in different time points to evaluate the change of phosphorylation of Akt in USP9X inhibitors treated platelets. 【Results】 Both human and mouse platelets expressed USP9X. Compared to the young mice, the old mice showed significantly enhanced expression of USP9X(P<0.05). To assess the effect of USP9X on platelet function, USP9X inhibitor was used to pre-incubate platelets for 30 min and platelet function were examined later. Results showed that USP9X inhibitor significantly decreased platelet activation including aggregation, ATP release and spreading(P<0.05). Compared to the control group, the inhibitor treated group showed a significant decrease in the spreading area after 45 minutes. The Western blot results showed a significant decrease in Akt phosphorylation levels of platelets in the USP9X inhibitor treated group. 【Conclusion】 Both human and mouse platelet express USP9X, and inhibition of USP9X decreased platelet function including aggregation, ATP release and spreading. USP9X can also influence the phosphorylation of Akt. The inhibitor of USP9X may become a potential therapeutic target for thrombosis intervention.