The cystine knot (CK) motif comprises an internal ring formed by two disulfide bonds and their connecting backbone segments which is threaded by a third disulfide bond .It is present in peptides and proteins of a variety of species ,in-cluding fungi ,plants ,marine molluscs ,insects and spiders .CK polypeptide is one of the ideal model molecules for drug design and molecular engineering research because of its stable structure and variety of bioactivities .Here we summarized the main structural features of both inhibitor cystine knot (ICK) peptide and cyclic cystine knot (CCK) peptide ,including primary se-quence ,topology ,permutation ,synthesis and folding characteristics ,as well as its applications on drug design and molecular engineering .

Objective To explore the research hotspots and trends in the field of cognitive dysfunction after aneurysmal subarachnoid hemorrhage (aSAH) based on bibliometric analysis. Methods Tools such as VoSviewer, CiteSpace, and the R language Bibliometrix package were utilized to conduct a bibliometric analysis of literature related to cognitive dysfunction after aSAH retrieved from the Web of Science Core Collection (WoSCC) database, spanning from January 1, 1991, to December 31, 2023. Results A total of 262 articles involving 44 countries, 443 institutions, and 1, 328 authors were screened based on the search strategy. The United States was the country with the highest number of articles (72) and the most international collaboration. The University of Toronto was the most productive institution (18 articles). Neurosurgery and World Neurosurgery were the journals with the highest number of publications in this field, each contributing 15 articles. The articles published in Stroke were the highest in total citation frequency, with 1, 222 citations. MACDONALD R L was the most prolific author in this field (17 articles), while WONG G K C had the highest co-citation frequency (179 times). Currently, the research hotspots in cognitive dysfunction after aSAH focused on early brain injury (EBI), delayed cerebral ischemia (DCI), and cerebral vasospasm (CV). The mechanism of DCI's impact on cognitive dysfunction after aSAH represented one of the research trends in this field. Conclusion The current research hotspots in the field of cognitive dysfunction after aSAH concentrate on pathophysiological processes such as EBI, CV, and DCI. The exploration of mechanisms underlying pathophysiological changes after aSAH remains a focal point for future research in this area.

OBJECTIVETo investigate the effect of Src kinase inhibitor PP2 on hypoxia/reoxygenation (H/R) injury in rat astrocytes in vitro.

METHODSIn vitro cultured rat astrocytes were exposed to hypoxia for 8 h followed by reoxygenation for 24 h with or without pretreatment with PP2 (10 µmol/L) for 24 h before H/R injury. MTT assay and flow cytometry were used to detect the viability and apoptosis of the exposed astrocytes, respectively, and the protein expressions of Src, Bax, and Bcl-2 in the cells were determined using Western blotting.

RESULTSPP2 pretreatment significantly increased the viability and decreased the apoptosis rate of rat astrocytes exposed to H/R injury (P<0.01). Western blotting showed that H/R injury caused increased expression of Src kinase, which was lowered by PP2 pretreatment. The ratio of Bax/bcl-2 in the astrocytes increased after H/R injury, and was significantly decreased by PP2 pretreatment (P<0.01).

CONCLUSIONPP2 protects rat astrocytes from H/R injury possibly by inhibiting the expression of Src kinase and activating the anti-apoptotic mechanisms in the cells.

Animals ; Apoptosis ; Astrocytes ; pathology ; Cell Hypoxia ; Cells, Cultured ; Flow Cytometry ; Pyrimidines ; pharmacology ; Rats ; src-Family Kinases ; antagonists & inhibitors

OBJECTIVETo determine the expression of connexin 43 (Cx43) protein and explore the functional modulation of gap junction intercellular communication in astrocytes.

METHODSCultured neonatal SD rat astrocytes were divided into normal control group, all-trans retinoic acid (ATRA) group (treated with 10 µmol/L ATRA for 24 h) and oleamide group (treated with 25 µmol/L oleamide for 2 h). Western blotting and immunofluorescence assay were used to detect total cellular Cx43 protein expression and Cx43 expression on the surface of the astrocytes, respectively. Parachute assay was used to evaluate the functional changes of gap junction intercellular communication of the astrocytes.

RESULTSCompared with the normal control cells, ATRA treatment resulted in a significantly increased expression of total Cx43 protein in the astrocytes (P<0.01), and oleamide significantly suppressed its expression (P<0.01). Similarly, ATRA obviously enhanced while oleamide suppressed Cx43 protein expression on the surface of the astrocytes. The gap junction intercellular communication of the astrocytes was enhanced by ATRA (P<0.01) and inhibited by oleamide (P<0.01).

CONCLUSIONATRA and oleamide can modulate gap junction intercellular communication of the astrocytes possibly by regulating the expression of Cx43 protein.

Animals ; Astrocytes ; metabolism ; Cell Communication ; drug effects ; Cells, Cultured ; Connexin 43 ; metabolism ; Gap Junctions ; metabolism ; Oleic Acids ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Tretinoin ; pharmacology

Objective:To evaluate the clinical value of NG-Test Carba5 for rapid detection of carbapenemases produced by carbapenem-resistant Enterobacteriaceae (CRE) strains. Methods:A total of 1 210 CRE strains were collected during 2018-2022 from 77 hospitals in 21 provinces of China and were subjected to NG-Test Carba5 for rapid detection of carbapenemase. The whole genome sequencing (WGS) analysis was referenced as the gold standard method.Results:Overall, the NG-Test Carba5 demonstrated excellent performance in detection of five kinds of carbapenemases [Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), imipenemase metallo-β-lactamase (IMP), Verona integron-encoded metallo-beta-lactamase (VIM) and oxacillinase-48-type carbapenemases(OXA-48)] from CRE strains, with a sensitivity of 98.47% (1 161/1 179), specificity of 100% (31/31), and positive predictive value of 100% (1 161/1 161). The sensitivity for detection of NDM, IMP, OXA and VIM reached 100% (307/307), and 97.70% (763/781) for KPC. For 11 strains carrying blaKPC-25, blaKPC-78, or blaKPC-93, NG-Test Carba5 reported positive KPC detection (11/11). For strains carrying blaKPC-33 and blaKPC-77, however, NG-Test Carba5 delivered negative results. Additionally, for those strains co-producing two or three kinds of carbapenemases, NG-Test Carba5 was able to report all of the targets with a sensitivity of 100% (91/91). Conclusions:NG-Test Carba5 showed excellent performance in rapid and accurate detection of carbapenemases from CRE strains. Nonetheless, for those strains with negative results, some other phenotypic and genotypic methods should be implemented alongside to avoid missing targets.

Objective To investigate the effect of Src kinase inhibitor PP2 on hypoxia/reoxygenation (H/R) injury in rat astrocytes in vitro. Methods In vitro cultured rat astrocytes were exposed to hypoxia for 8 h followed by reoxygenation for 24 h with or without pretreatment with PP2 (10 μmol/L) for 24 h before H/R injury. MTT assay and flow cytometry were used to detect the viability and apoptosis of the exposed astrocytes, respectively, and the protein expressions of Src, Bax, and Bcl-2 in the cells were determined using Western blotting. Results PP2 pretreatment significantly increased the viability and decreased the apoptosis rate of rat astrocytes exposed to H/R injury (P<0.01). Western blotting showed that H/R injury caused increased expression of Src kinase, which was lowered by PP2 pretreatment. The ratio of Bax/bcl-2 in the astrocytes increased after H/R injury, and was significantly decreased by PP2 pretreatment (P<0.01). Conclusion PP2 protects rat astrocytes from H/R injury possibly by inhibiting the expression of Src kinase and activating the anti-apoptotic mechanisms in the cells.

Objective To investigate the effect of Src kinase inhibitor PP2 on hypoxia/reoxygenation (H/R) injury in rat astrocytes in vitro. Methods In vitro cultured rat astrocytes were exposed to hypoxia for 8 h followed by reoxygenation for 24 h with or without pretreatment with PP2 (10 μmol/L) for 24 h before H/R injury. MTT assay and flow cytometry were used to detect the viability and apoptosis of the exposed astrocytes, respectively, and the protein expressions of Src, Bax, and Bcl-2 in the cells were determined using Western blotting. Results PP2 pretreatment significantly increased the viability and decreased the apoptosis rate of rat astrocytes exposed to H/R injury (P<0.01). Western blotting showed that H/R injury caused increased expression of Src kinase, which was lowered by PP2 pretreatment. The ratio of Bax/bcl-2 in the astrocytes increased after H/R injury, and was significantly decreased by PP2 pretreatment (P<0.01). Conclusion PP2 protects rat astrocytes from H/R injury possibly by inhibiting the expression of Src kinase and activating the anti-apoptotic mechanisms in the cells.

Objective To observe the effect of a walking correcting tape on the kinematics and temporal-spatial indicators of gait after a stroke. Methods Thirty hemiplegic stroke survivors were randomly divided into a control group ( n=15) and a correcting tape group ( n=15) . In addition to their routine rehabilitation program, the control group received 30 minutes of walking training five times a week for 3 weeks with any necessary oral guidance and posture correction. The correcting tape group performed the same walking training assisted by a self-made walking correcting tape. Before and after the treatment, the kinematics and temporal-spatial indicators of both groups were quantified using three-dimensional gait analysis. Results After the treatment, the peak angles of hip and knee flex-ion were significantly higher in the taped group than in the control group and in the taped group before the treatment ( P≤0.05) . After the treatment, the walking speeds, stride frequencies and stride lengths of both groups were signifi-cantly better than before the treatment, but those of the former group were all significantly better than the latter ( P≤0.05 for both) . Conclusions Correcting tape can improve the peak angles of hip and knee flexion of hemiplegic legs and improve the walking capacity of stroke patients.

OBJECTIVE: To investigate the expression of LINC01106 in colorectal cancer and its role in regulating the proliferation and apoptosis of colorectal cancer cells. METHODS: We analyzed the data of LINC01106 expression levels in tumor tissues and normal tissues of patients with colorectal cancer in TCGA database and explored the association of LINC01106 expression level with the prognosis of the patients. Colorectal cancer SW480 cell lines with LINC01106 knockdown or overexpression were established, and their proliferation and apoptosis relative to the parental cells were evaluated using CCK-8 assay and flow cytometry, respectively. The expressions of p-STAT3, STAT3, and Bcl-2 in the cells were detected by immunoblotting. Nude mouse models bearing xenografts of SW480 cells with LINC01106 knockdown or na?ve SW480 cells were established to observe the effect of LINC01106 knockdown on the growth of SW480 cells . RESULTS: Analysis of the data from TCGA database showed that the expression level of LINC01106 was significantly higher in colorectal cancer tissues than in normal tissues, and LINC01106 expression level was significantly related to the prognosis of the patients ( < 0.05). Knockdown of LINC01106 significantly inhibited the proliferation and promoted apoptosis of SW480 cells ( < 0.05), while LINC01106 overexpression significantly promoted proliferation of the cells. LINC01106 knockdown in SW-480 cells obviously lowered the expressions of p- STAT3 and Bcl-2 and suppressed the growth of the xenograft in nude mice. CONCLUSIONS LINC01106 is significantly up-regulated in colorectal cancer tissue and is related to the prognosis of the patients. LINC01106 can regulate the proliferation and apoptosis of SW480 cells through STAT3/Bcl-2 signaling and may serve as a potential marker for the diagnosis and prognostic evaluation of colorectal cancer.

BACKGROUND: Thymic carcinomas (TCs) and thymic neuroendocrine neoplasms (TNENs) are two aggressive subtypes of thymic malignancy. Traditional therapy for advanced TCs and TNENs has limited outcome. New genomic profiling of TCs and TNENs might provide insights that contribute to the development of new treatment approaches. METHODS: We used gene panel sequencing technologies to investigate the genetic aberrations of 32 TC patients and 15 TNEN patients who underwent surgery at Shanghai Chest Hospital between 2015 and 2017. Patient samples were sequenced using a 324-gene platform with licensed technologies. In this study, we focused on clinically relevant genomic alterations (CRGAs), which are previously proven to be pathogenic alterations, to identify the pathology-specific mutational patterns, prognostic signatures of TCs and TNENs. RESULTS: The mutational profiles between TCs and TNENs were diverse. The genetic alterations that ranked highest in TCs were in CDKN2A, TP53, ASXL1, CDKN2B, PIK3C2G, PTCH1, and ROS1 , while those in TNENs were in MEN1, MLL2, APC, RB1 , and TSC2 . Prognostic analysis showed that mutations of ROS1, CDKN2A, CDKN2B, BRAF, and BAP1 were significantly associated with worse outcomes in TC patients, and that mutation of ERBB2 indicated shortened disease-free survival (DFS) and overall survival (OS) in TNEN patients. Further investigation found that the prognosis-related genes were focused on signal pathways of cell cycle control, chromatin remodeling/DNA methylation, phosphoinositide 3-kinases (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), and receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase (MAPK) signaling. CONCLUSION We profiled the mutational features of 47 Chinese patients with thymic malignancy of diverse pathologic phenotypes to uncover the integrated genomic landscape of these rare tumors, and identified the pathology-specific mutational patterns, prognostic signatures, and potential therapeutic targets for TCs and TNENs.
Humans ; Thymoma ; Protein-Tyrosine Kinases/genetics* ; Proto-Oncogene Proteins/genetics* ; China ; Thymus Neoplasms/pathology* ; Prognosis ; Neuroendocrine Tumors/pathology* ; Mutation/genetics*