BACKGROUND:Artificially synthesized hydroxyapatite ceramic granules are widely used in clinical practice to repair large-volume bone defects.However,the osteogenic effect of hydroxyapatite ceramic granules prepared by high-temperature sintering is limited by their low degradability and bioactivity. OBJECTIVE:To prepare biomimetically precipitated nanocrystalline calcium phosphate granules by a novel low-temperature deposition technique,and to characterize their physicochemical properties and cytocompatibility. METHODS:Biomimetically precipitated nanocrystalline calcium phosphate granules were prepared using a modified supersaturated calcium phosphate mineralization solution and a repeated settling and decantation washing method.Hydroxyapatite bioceramic granules were used as the control.The morphology and phase composition of the granules were characterized by scanning electron microscopy,X-ray diffraction,and Fourier transform infrared spectroscopy.The specific surface area,porosity distribution,hardness and hydrophilicity of the granules were characterized by BET-N2 method,hardness test,and contact angle test.The adsorption properties of the granules for bovine serum albumin and fetal bovine serum protein were determined by bicinchoninic acid assay.The two kinds of granules or granule extracts were co-cultured with human umbilical cord mesenchymal stem cells,and the cell proliferation was detected by MTT assay. RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the surface of the two kinds of particles was slightly rough and accompanied by tiny particles,the surface of the hydroxyapatite bioceramic particles was dense and smooth,and the biomimetically precipitated nanocrystalline calcium phosphate granules were mainly composed of needle/plate crystals with non-uniform nanometer size,and formed a nanopore structure between the crystals.X-ray diffraction and Fourier transform infrared spectroscopy exhibited that compared with hydroxyapatite bioceramic granules,biomimetically precipitated nanocrystalline calcium phosphate granules had smaller crystalline particles,lower crystallinity,and more binding water and carbonic acid groups.Compared with hydroxyapatite bioceramic granules,biomimetically precipitated nanocrystalline calcium phosphate granules had higher specific surface area,better hydrophilicity,lower hardness,and higher protein adsorption capacity.(2)The results of MTT assay showed that the two kinds of granule extracts had no cytotoxicity,human umbilical cord mesenchymal stem cells survived well on the surface of the two kinds of granules,and the biomimetically precipitated nanocrystalline calcium phosphate granules had stronger cell proliferation activity.(3)These findings indicate that compared with hydroxyapatite bioceramic granules,biomimetically precipitated nanocrystalline calcium phosphate granules have better physicochemical properties and cytocompatibility.

Autophagy is an important mechanism to maintain cellular function and metabolism,whereas ab-normal autophagy can cause the advent and worsening of various diseases.N6-Methyladenosine(m6A)RNA methylation is a reversible RNA modification,which is regulated by m6A methyltransferase,m6A demethylase and m6A-binding protein.Studies have shown that autophagy-related genes promote or attenuate autophagy level dependent on the regulation of m6A,and then participate in the process of diseases.This paper reviews the progress of m6A modification regulatory enzymes and their binding proteins in regulating cell autophagy to provide reference for future researches.

Myocardial infarction is the most common cause of heart failure,and myocardial remodeling can occur after infarction,thus contributing to the progression of heart failure.The occurrence of post-infarction ventricular remode-ling is closely related to m6A methylation.m6A methylation is a reversible and highly dynamic process.This process is mainly mediated by m6A methylation positive and negative regulatory enzymes and is involved in the occurrence of post-in-farction myocardial remodeling through mechanisms such as cellular autophagy.This article mainly reviews relevant litera-ture in recent years.Firstly,a brief introduction is given to m6A methylation,followed by an introduction to the role of m6A methylase in regulating myocardial remodeling.Finally,a summary analysis is conducted on the mechanism of m6A methylation in regulating myocardial remodeling from the perspectives of autophagy,inflammation,cell apoptosis,calcium ion homeostasis,extracellular matrix remodeling,and ferroptosis.The feasibility of using m6A methylation serological de-tection as a diagnostic tool for myocardial remodeling after myocardial infarction is discussed,in order to provide reference for related research.

Objective To investigate the effects and mechanism of Zhachong Shisanwei Pills on rats with cerebral ischemia.Methods Totally 75 rats were randomly divided into sham-operation group,model group,positive drug group(Ginaton,21.6 mg/kg),and Zhachong Shisanwei Pills low-,medium-,and high-dosage groups(81,162,324 mg/kg).Each treatment group was given the corresponding drug by gavage for 5 days.On the 6th day,a cerebral ischemia rat model was prepared by suture method.After 24 hours of modeling,the drugs were given in the same manner for 2 days.Neurological function scoring,horizontal beam walking scoring,and grip strength testing were performed on rats.TTC staining was used to detect the cerebral infarction rate,HE staining and Nissl staining were used to observe the morphology of brain tissue.TUNEL staining was used to detect the apoptosis rate of brain tissue cells.Differential genes in the treatment of cerebral ischemia using Zhachong Shisanwei Pills were screened by transcriptomics,and RT-qPCR,immunohistochemistry and Western blot were used to detect differential gene mRNA and protein expression.Results Compared with the sham-operation group,the model group rats showed a decrease in neurological function scores,horizontal beam walking scores,grip strength,an increase in cerebral infarction rate,neuronal nucleus condensation,vacuolar changes,widened intercellular spaces,the number of Nissl bodies reduced,and the apoptosis rate increased(P<0.01,P<0.001);compared with the model group,the Zhachong Shisanwei Pills medium-dosage group showed an increase in neurological function score,horizontal beam walking score,and grip strength in rats,a decrease in cerebral infarction rate,a lower degree of neuronal damage,an increase in the number of Nissl bodies,and a decrease in cell apoptosis rate(P<0.05,P<0.01).Transcriptome and bioinformatics analysis screened the Hippo signaling pathway related to the anti-cerebral ischemia effect of Zhachong Shisanwei Pills.The key genes of this pathway,mammalian sterile line 20 like kinase(MST1)1,Yes related protein(YAP)1,large tumor suppressor kinase(LATS)1,and TEA domain family member(TEAD)1 were detected.The results showed that the expression of MST1 mRNA and protein in brain tissue of model rats significantly increased,while the expressions of YAP1,LATS1,TEAD1 mRNA and protein significantly decreased;Zhachong Shisanwei Pills could down-regulate the expression of MST1 in brain tissue of model rats,and up-regulate the expressions of YAP1,LATS1 and TEAD1.Conclusion Zhachong Shisanwei Pills may exert anti-cerebral ischemia effects through the Hippo signaling pathway.

Humans ; HIV-1/genetics* ; Anti-Retroviral Agents/therapeutic use* ; Mutation/genetics* ; Treatment Failure ; HIV Infections/genetics* ; Drug Resistance, Viral/genetics* ; Anti-HIV Agents/therapeutic use* ; Genotype

Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy. Isocitrate dehydrogenases (IDHs) are a class of key proteins in energy metabolism, including IDH1, IDH2, and IDH3, which are involved in the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG). Mutants of IDH1 or IDH2 can produce d-2-hydroxyglutarate (D-2HG) with α-KG as the substrate, and then mediate the occurrence and development of cancer. At present, no IDH3 mutation has been reported. The results of pan-cancer research showed that IDH1 has a higher mutation frequency and involves more cancer types than IDH2, implying IDH1 as a promising anti-cancer target. Therefore, in this review, we summarized the regulatory mechanisms of IDH1 on cancer from four aspects: metabolic reprogramming, epigenetics, immune microenvironment, and phenotypic changes, which will provide guidance for the understanding of IDH1 and exploring leading-edge targeted treatment strategies. In addition, we also reviewed available IDH1 inhibitors so far. The detailed clinical trial results and diverse structures of preclinical candidates illustrated here will provide a deep insight into the research for the treatment of IDH1-related cancers.

Objective:To analyze the preoperative and postoperative color Doppler ultrasonographic features of Abernethy malformation in children, and to investigate the value of ultrasound diagnosis of Abernethy malformation and postoperative complications.Methods:A retrospective analysis was performed on the clinical and ultrasound data of twelve cases of Abernethy malformation confirmed by surgical treatment in the General Surgery Department of the Children′s Hospital Affiliated to Capital Institute of Pediatrics from February 2017 to November 2021. A comparison was made between preoperative ultrasound and intraoperative portal vein angiography after shunt ligation to explore the accuracy of preoperative ultrasound in diagnosing Abernethy malformation; The common location of thrombosis after shunt ligation was summarized by comparing postoperative ultrasound with CT angiography.Results:Preoperative ultrasonography showed no main portal vein or cable shape in 9 cases, and they were diagnosed as probable Abernethy type Ⅰ; The main portal vein was narrow in 3 cases, and they were diagnosed as Abernethy type Ⅱ. The main portal veins of 11 case were developing and they were confirmed as Abernethy malformation type Ⅱ by portal vein angiography after blocking of portosystemic shunt; the main portal vein of 1 case was not developing which was confirmed as Abernethy type Ⅰ. The classification accuracy of preoperative ultrasound diagnosis of Abernethy malformation was 33.3%. Preoperative ultrasound diagnosis of shunt vessel location: the coarse inferior mesenteric veins of 7 cases flowed into the iliac vein, the coarse inferior mesenteric vein of 1 case flowed into the inferior vena cava, splenic vein and superior mesenteric vein converged and flowed into inferior vena cava in 2 cases, splenic vein and left renal vein communicated in 2 cases. The location of shunt vessels diagnosed by portal vein X-ray angiography was basically consistent with preoperative ultrasonography. At the same time, inferior mesenteric vein shunt combined with tortuous and dilated vein network on colorectal surface was observed. After ligation of shunt vessels, all of shunt vessels were occluded or thrombolized in varying degrees.Splenic vein retropancreatic segment of three cases occured secondary thrombosis, and one case of blocked portal vein occured secondary cavernous change. All the thrombi were confirmed by CT angiography.Conclusions:①The main portal vein of Abernethy malformation type Ⅱ is tenuous, and is easily misdiagnosed Abernethy malformation type Ⅰ by preoperative ultrasound examination; ②Preoperative ultrasound can determine the location of Abernethy malformed shunt vessels; ③The shunt between the inferior mesenteric vein-iliac vein/inferior vena cava should be emphatically explored in children with recurrent hematochezia; ④Postoperative ultrasound can detect portal vein thrombosis early and provide help for clinical anticoagulant therapy.

Objective:To investigate the value of ADC derived from DWI combined with texture analysis derived from T 2WI fat suppressed images in distinguishing benign and malignant soft tissue tumors. Methods:The MRI and DWI images of 94 patients with soft tissue tumors (44 cases with malignant and 50 cases with benign) confirmed by pathology were analyzed retrospectively in the First Affiliated Hospital of USTC West District. ADC values of solid components were measured at GE ADW4.6 workstation. The texture features were extracted by manually drawing the ROI on the maximum level of the T 2WI fat suppressed images; the ADC values and texture parameters between the two groups were statistically analyzed by SPSS17.0, and the multivariate logistic regression model were conducted to analyze and calculate the diagnostic performance. Results:ADC value of benign and malignant soft tissue tumors was (1.6±0.3)×10 -3 mm 2/s, (1.2±0.5)×10 -3 mm 2/s, respectively, and the difference was statistically significant( t=-5.382, P<0.05). Taking 1.28×10 -3 mm 2/s as the critical value, the area under curve (AUC) for the diagnosis of benign and malignant soft tissue tumors was 0.783, the sensitivity was 92.00%, and the specificity was 65.91%. Among the texture features, the AUC of frequency size, skewness, Inertia All Direction_offset7, Inverse Difference Moment angle0_offset1, Inverse Difference Moment angle0_offset7 and Haralick Correlation All Direction_offset4_SD distinguishing benign and malignant soft tissue tumors were 0.825, 0.739, 0.826, 0.816, 0.820 and 0.783, respectively. The AUC, sensitivity and specificity of the best predictive model distinguishing benign and malignant soft tissue tumors were 0.930, 88.00% and 86.36% respectively using multivariate logistic regression analysis. Conclusion:ADC combined with texture analysis is of great value in preoperative differentiation of benign and malignant soft tissue tumors.

SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used anti-viral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further and studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.

Linalool is an important monoterpene, and widely used in food, pharmaceutical and cosmetic industry. The low concentration in plants and the difficulties in extraction restrict its large scale production. Saccharomyces cerevisiae can provide the monoterpene precursor, geranyl diphosphate (GPP) through its endogenous isoprenoid pathway. Therefore, it could be used as the host for monoterpene production. However, the weak metabolic flux through the isoprenoid pathway leads to the insufficient supply of GPP, and results in low monoterpene productivity. In order to increase the metabolic flux, we constructed the integrated expression plasmid pRS305-tHMG1 and free expression plasmid pYLIS-IDI1 to enhance the expression levels of isopentenyl diphosphate isomerase (IDI1) and a truncated 3-hydroxyl-3-methylglutaryl-CoA reductase gene (tHMG1). The two plasmids were separately transformed into S. cerevisiae CEN.PK2-1C, resulting in strains LS01 and LS02. The plasmid pYLIS-IDI1 was further transformed into strain LS01, resulting in strain LS03. GC-MS analysis showed that the linalool concentration was increased by 1.3 times and reached (127.71 +/- 7.68) microg/L. In conclusion, enhancement of the supply of GPP precursors through the regulation of isoprenoid pathway could increase the linalool production in S. cerevisiae.
Biosynthetic Pathways ; genetics ; Butadienes ; metabolism ; Hemiterpenes ; metabolism ; Monoterpenes ; metabolism ; Pentanes ; metabolism ; Saccharomyces cerevisiae ; genetics ; metabolism