2-Methylcitrate cycle: a well-regulated controller of Bacillus sporulation.

Bacillus thuringiensis is the most widely used eco-friendly biopesticide, containing two primary determinants of biocontrol, endospore and insecticidal crystal proteins (ICPs). The 2-methylcitrate cycle is a widespread carbon metabolic pathway playing a crucial role in channelling propionyl-CoA, but with poorly understood metabolic regulatory mechanisms. Here, we dissect the transcriptional regulation of the 2-methylcitrate cycle operon prpCDB and report its unprecedented role in controlling the sporulation process of B. thuringiensis. We found that the transcriptional activity of the prp operon encoding the three critical enzymes PrpC, PrpD, and PrpB in the 2-methylcitrate cycle was negatively regulated by the two global transcription factors CcpA and AbrB, while positively regulated by the LysR family regulator CcpC, which jointly account for the fact that the 2-methylcitrate cycle is specifically and highly active in the stationary phase of growth. We also found that the prpD mutant accumulated 2-methylcitrate, the intermediate metabolite of the 2-methylcitrate cycle, which delayed and inhibited sporulation at the early stage. Thus, our results not only revealed sophisticated transcriptional regulatory mechanisms for the metabolic 2-methylcitrate cycle but also identified 2-methylcitrate as a novel regulator of sporulation in B. thuringiensis.

Synergistic enhancement of bone regeneration by LMP-1 and HIF-1α delivered by adipose derived stem cells.

OBJECTIVES: To investigate the effect of the combination of LMP-1 and HIF-1α delivered by adipose-derived stem cells (ADSCs) on osteogenesis in vitro and in vivo. RESULTS: Cells expressing both LMP-1 and HIF-1α genes had elevated mRNA expression of BMP-2, RunX2, alkaline phosphatase, osteocalcin, collagen I and alkaline phosphatase activity compared to cells from other groups. Furthermore, mineralization at day 14 in the cells expressing both LMP-1 and HIF-1α was significantly higher than in all the other groups. In vivo, H&E staining and immunohistochemical analysis of the cell-scaffolds also showed more ectopic bone formation at 4 weeks compared to other groups. More new vessel formation was apparent in the pLVX-rHIF-1α and pLVX-rLMP-1-rHIF-1α groups. CONCLUSION: LMP-1 and HIF-1α gene delivery synergistically enhanced the osteo-differentiation of ADSCs in vitro and promoted osteogenesis in vivo compared with LMP-1 alone or HIF-1α alone.

The metabolic regulation of sporulation and parasporal crystal formation in Bacillus thuringiensis revealed by transcriptomics and proteomics.

Bacillus thuringiensis is a well-known entomopathogenic bacterium used worldwide as an environmentally compatible biopesticide. During sporulation, B. thuringiensis accumulates a large number of parasporal crystals consisting of insecticidal crystal proteins (ICPs) that can account for nearly 20-30% of the cell's dry weight. However, the metabolic regulation mechanisms of ICP synthesis remain to be elucidated. In this study, the combined efforts in transcriptomics and proteomics mainly uncovered the following 6 metabolic regulation mechanisms: (1) proteases and the amino acid metabolism (particularly, the branched-chain amino acids) became more active during sporulation; (2) stored poly-ß-hydroxybutyrate and acetoin, together with some low-quality substances provided considerable carbon and energy sources for sporulation and parasporal crystal formation; (3) the pentose phosphate shunt demonstrated an interesting regulation mechanism involving gluconate when CT-43 cells were grown in GYS medium; (4) the tricarboxylic acid cycle was significantly modified during sporulation; (5) an obvious increase in the quantitative levels of enzymes and cytochromes involved in energy production via the electron transport system was observed; (6) most F0F1-ATPase subunits were remarkably up-regulated during sporulation. This study, for the first time, systematically reveals the metabolic regulation mechanisms involved in the supply of amino acids, carbon substances, and energy for B. thuringiensis spore and parasporal crystal formation at both the transcriptional and translational levels.

Pure platelet-rich plasma promotes semaphorin-3A expression: a novel insight to ameliorate intervertebral disk degeneration in vitro.

INTRODUCTION: Intervertebral disk degeneration (IVDD) can be effectively treated using platelet-rich plasma (PRP). While the exact process is fully understood, it is believed that using pure PRP (P-PRP) without leukocytes is a better option for preventing IVDD. Semaphorin-3A (Sema3A), an inhibitor of angiogenesis and innervation, is essential for preserving IVDD's homeostasis. Whether PRP prevents IVDD by modifying Sema3A has yet to receive much research. This work aims to clarify how P-PRP affects Sema3A when IVDD develops in vitro. METHODS: Nucleus pulposus cells (NPCs) isolated from 8-week-old male Sprague-Dawley rats were exposed to 10 ng/ml IL-1ß and then treated with P-PRP or leukocyte platelet-rich plasma (L-PRP) in vitro, followed by measuring cell proliferation, apoptosis and microstructures, inflammatory gene and Sema3A expression, as well as anabolic and catabolic protein expression by immunostaining, quantitative real-time polymerase chain reaction (qPCR), western blot, and enzyme-linked immunosorbent assay (ELISA). RESULTS: In comparison with L-PRP, P-PRP had a higher concentration of growth factors but a lower concentration of inflammatory substances. P-PRP increased the proliferation of NPCs, while IL-1 relieved the amount of apoptosis due to its intervention. Anabolic genes, aggrecan, and collagen II had higher expression levels. MMP-3 and ADAMTS-4, two catabolic or inflammatory genes, showed lower expression levels. Sema3A activity was enhanced after P-PRP injection, whereas CD31 and NF200 expression levels were suppressed. CONCLUSIONS: P-PRP enhanced the performance of NPCs in IVDD by modifying the NF-κB signaling pathway and encouraging Sema3A expression, which may offer new therapy options for IVDD. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The findings provide a new therapeutic target for the treatment of IVDD and show a novel light on the probable mechanism of PRP and the function of Sema3A in the progression of IVDD.

Topological Alterations of Working Memory Impairment in Aged Patients With Vascular Dementia.

Aneurysmal subarachnoid hemorrhage (aSAH) is a common disease causing vascular dementia. Survivors often suffer from cognitive impairment especially working memory deficit. Currently, lack of theoretical support limits the improvement of cognitive intervention or rehabilitation. It is unclear how the large-scale network differs and to what extent is the brain network affected? Our study aims to provide novel information about the topological characteristics of brain organization, especially "small-world" property. A total of 62 aSAH patients are enrolled in this study. They are divided into two groups according to the syndrome of working memory deficit. Their working memory function is evaluated by TMT-B and AVLT (Chinese version). Functional MRI scan is also performed for detecting resting-state cortical plasticity. We utilized ICA to extract functional sub-networks including working memory network from imaging data. And then we establish binarized network and calculate the small-worldness property as well as local and global efficiency of networks. aSAH group with working memory deficit shows no significant difference of clustering coefficient with control group. Our study discovered significant decrease of characteristic path length indicating an increase of overall routing efficiency. We reason that patients with working memory deficit have to recruit more neuronal resources and thus develops higher overall routing efficiency of local network. This study provides novel information about the neural alterations of aSAH patients with working memory deficit. It might contribute to the understanding of neural mechanism and the improvement of current intervention for vascular dementia.

Detection of Escherichia coli enoyl-ACP reductase using biarsenical-tetracysteine motif.

Although the tetracysteine (TC) motif has been used as a tag, the binding stability between TC motif and biarsenical reagent against extreme conditions as well as its capacity as a quantitative tag remains not well developed. To reveal these problems, we chose enoyl-acyl carrier protein reductase (FabI), which was involved in the final step of elongation in the bacterial fatty acid biosynthesis, to be tagged by the TC motif. Taking enhanced green fluorescent protein (EGFP) tagged FabI as a control, we investigated the activities of various TC tagged FabIs (N-terminus, C-terminus, or both N- and C-terminus TC motif). The results showed that all the TC tagged FabIs had high enzyme activities while the EGFP tagged FabI exhaustively lost the activity. Beside this, the characteristics of the tag, including labeling stability against extreme conditions, capacity for quantitative analysis, and ability for in-cell labeling, were also investigated. We demonstrated for the first time that the binding between FlAsH reagent and TC motif was stable against high pressure, high field strength, high temperature, and ultrasound. Furthermore, we verified the potential of TC motif for quantitative analysis of target protein by different approaches, including SDS-PAGE, spectrofluorometry (SPF), and capillary zone electrophoresis (CZE).

Prolonged dual antiplatelet therapy improves clinical outcomes in high-risk patients implanted with sirolimus-eluting stents.

BACKGROUND: Although a science advisory recommending 12 months of dual antiplatelet therapy after drug-eluting stents implantation was published recently, the optimal duration of dual antiplatelet therapy has not yet been precisely determined. HYPOTHESIS: Prolonged dual antiplatelet therapy can improve clinical outcomes in high-risk patients implanted with sirolimus-eluting stents. METHODS: The patients implanted with sirolimus-eluting stents were assigned into standard clopidogrel therapy group (clopidogrel 75 mg/d for 12 mo) and prolonged clopidogrel therapy group (clopidogrel 75 mg/d for 18 mo). Long-term aspirin (100 mg/d) therapy was adopted in both groups. The primary endpoint was very late stent thrombosis. RESULTS: After 12 months, 24 patients were excluded because of major adverse cardiovascular events (MACEs). Three hundred and thirty six patients surviving without MACEs were further followed up for 6 months. Between 12 and 18 months, in 160 patients with standard clopidogrel therapy, 5.6% had very late stent thrombosis. In contrast, in 176 patients with prolonged clopidogrel therapy, 1.1% had very late stent thrombosis (p<0.01, versus standard clopidogrel therapy group). CONCLUSIONS: Prolonged dual antiplatelet therapy may be beneficial to prevent very late stent thrombosis after sirolimus-eluting stents implantation in high-risk patients.

Esthetic outcomes of socket-shield technique for immediate implantation in the maxillary anterior zone and its effect on gingival morphology / 中国基层医药

Objective:To investigate the esthetic outcomes of socket-shield technique (SST) for immediate implantation in the maxillary anterior zone and its effect on gingival morphology.Methods:This case-control study included 75 patients with maxillary anterior tooth defects who were treated at Huzhou Central Hospital between January 2019 and September 2021. Based on their respective treatment methods, these patients were divided into two groups: SST implantation ( n = 30) and immediate implantation ( n = 45). All patients were followed up for 1 year. During this period, the thickness of the labial plate, pink esthetic score, probing depth, and patient satisfaction were compared between the two groups. Results:At 6 and 12 months post-surgery, the SST group exhibited significantly lower labial plate bone resorption [(0.24 ± 0.07) mm, (0.41 ± 0.10) mm] compared with the immediate implantation group [(0.56 ± 0.11) mm, (0.86 ± 0.15) mm, t = 14.12, 14.41, both P < 0.001]. Furthermore, at both time points, the SST group scored significantly higher in curvature, height, color, and texture of the labial gingival margin using the pink esthetic score scale ( t6 months = 7.13, 6.38, 5.45, 4.92; t12 months = 3.43, 2.92, 7.50, 6.25, all P < 0.05). The mesial and distal papilla scores did not differ significantly between the SST and immediate implantation groups at various time points (all P > 0.05). However, at 6 months post-surgery, the periodontal probing depth in the SST group was (1.21 ± 0.06) mm, which was significantly lower than the corresponding value of (1.92 ± 0.07) mm in the immediate implantation group ( t = 45.49, P < 0.001). By 12 months post-surgery, no significant difference in periodontal probing depth was observed between the two groups ( P > 0.05). Additionally, there was no significant difference in patient satisfaction between the SST and immediate implantation groups ( P > 0.05). Conclusion:SST effectively addresses insufficient labial bone mass and prevents bone resorption. Additionally, it is advantageous for restoring the morphology of the labial alveolar process and soft tissue level. Clinically, its application produces similar results to immediate implantation.

Effect of colchicine on LPS induced endothelial mesenchymal transformation and its mechanism / 中国药理学通报

Aim To investigate the effect of colchicine on lipopolysaccharide (LPS) induced endothelial to mesenchymal transition (EndMT) in human umbilical vein vascular endothelial cells (HUVECs) and its related mechanisms. Methods The EndMT model was established by treating HUVECs with LPS. Cell proliferation rate was detected by CCK-8 assay, cytotoxicity was detected by LDH assay, and the optimal drug concentration was screened. The cells were divided into the normal control group, the normal control + colchicine (10 nmol • L) group, the LPS (10 mg • L) model group, and the LPS + colchicine (10 nmol • L) group. The morphologic changes of the cells were observed under an inverted microscope, the cell migration ability was detected by Transwell assay, and the ability of tube formation was analyzed by tube formation assay. The expression of endothelial markers (CD31/ VE-cadherin) and mesenchymal cell markers (a-SMA/FSP-1) were detected by Western blot. NF-KB inhibitor was used to detect the changes in related signaling pathways. Results CCK-8 and LDH experiments showed that 10 nmol • L colchicine was the optimal concentration. LPS could induce morphological changes in HUVECs, and colchicine could reverse morphological changes in HUVECs to a certain extent. Transwell experiment showed that the migration ability of HUVECs in the LPS treatment group was significantly enhanced (P < 0. 05), and colchicine could significantly reverse this phenomenon (P < 0. 05) . Tube formation experiment showed that LPS decreased the endothelial tube formation ability of HUVECs (P < 0. 05), while colchicine treatment markedly improved LPS-induced tube formation defects (P < 0. 05) . Western blot assay showed that after colchicine co-cultured with LPS, the expression levels of CD31 and VE-cadherin significantly increased compared with the model group (P < 0. 05), while the expression levels of a-SMA and FSP-1 significantly decreased compared with the model group (P < 0. 05) . During the induction of EndMT by LPS, colchicine could inhibit the activation of the NF-KB/Snail signaling pathway. Conclusions Colchicine can effectively inhibit EndMT induced by LPS, and the mechanism may be related to the regulation of the NF-KB/Snail signaling pathway.

[Percutaneously full endoscopic decompressive laminectomy with precise localization for the treatment of lumbar spinal stenosis].

OBJECTIVE: To explore the feasibility of full endoscopic fenestration (FE-FE) via interlaminar approach for the treatment of lumbar spinal stenosis (LSS), and meanwhile, to analyze the related practicability and clinical outcome. METHODS: Referring to the traditional laminectomy and decompression, the lumbar spinal canal decompression was performed by using the water-medium spinal endoscopy (named FE-FE technique). Thirty-seven patients with LSS treated by FE-FE technique were retrospectively analyzed. There were 19 males and 18 females, aged from 55 to 83 years old with an average of (67.1±18.9) years. Visual analogue scale(VAS), Japanese Orthopaedic Association Scores(JOA), Oswestry Disability Index (ODI) and 36-Item Short-Form Health Survey (SF-36) were recorded. The patient's conscious pain and recovery of neurological function were observed, and the clinical efficacy was evaluated according to the improvement rate of JOA score. RESULTS: All 37 patients were followed up for 8 to 24 months with an average of (13.7±6.1) months. The postoperative follow-up and clinical evaluation for conscious pain and neurological function recovery showed that VAS, JOA, ODI and SF-36 scores were significantly improved compared with those before surgery(P<0.05). According to the improvement rate of JOA score to evaluate the clinical effects, at 6 months after opertion, the results were excellent in 17 cases, good in 13 cases, fair in 5 cases, and poor in 2 cases;and the last follow-up, the results were excellent in 19 cases, good in 13 cases, fair in 4 cases, and poor in 1 case. Postoperative imaging showed significant expansion of spine canal volume, and the followed-up clinical symptoms were improved satisfactorily, with the relief of lumbago and leg pain, improvement of daily life quality, and increased adaptability to social activities and no serious complications. CONCLUSIONS: Precise localization is the key to complete the canal decompression under full endoscopic surgery. FE-FE technique can effectively enlarge the narrow lumbar canal with less trauma, positive efficacy, safety and reliability. FE-FE has a broad application prospect though large cases and multi-center studies need to be further carried out.

Electrically controlled mass transport into microfluidic droplets from nanodroplet carriers with application in controlled nanoparticle flow synthesis.

Microfluidic droplets have been applied extensively as reaction vessels in a wide variety of chemical and biological applications. Typically, once the droplets are formed in a flow channel, it is a challenge to add new chemicals to the droplets for subsequent reactions in applications involving multiple processing steps. Here, we present a novel and versatile method that employs a high strength alternating electrical field to tunably transfer chemicals into microfluidic droplets using nanodroplets as chemical carriers. We show that the use of both continuous and cyclic burst square wave signals enables extremely sensitive control over the total amount of chemical added and, equally importantly, the rate of addition of the chemical from the nanodroplet carriers to the microfluidic droplets. An a priori theoretical model was developed to model the mass transport process under the convection-controlled scenario and compared with experimental results. We demonstrate an application of this method in the controlled preparation of gold nanoparticles by reducing chloroauric acid pre-loaded in microfluidic droplets with l-ascorbic acid supplied from miniemulsion nanodroplets. Under different field strengths, l-ascorbic acid is supplied in controllable quantities and addition rates, rendering the particle size and size distribution tunable. Finally, this method also enables multistep synthesis by the stepwise supply of miniemulsions containing different chemical species. We highlight this with a first report of a three-step Au-Pd core-shell nanoparticle synthesis under continuous flow conditions.

Casticin Attenuates Stemness in Cervical Cancer Stem-Like Cells by Regulating Activity and Expression of DNMT1 / 中国结合医学杂志

OBJECTIVE@#To explore whether casticin (CAS) suppresses stemness in cancer stem-like cells (CSLCs) obtained from human cervical cancer (CCSLCs) and the underlying mechanism.@*METHODS@#Spheres from HeLa and CaSki cells were used as CCSLCs. DNA methyltransferase 1 (DNMT1) activity and mRNA levels, self-renewal capability (Nanog and Sox2), and cancer stem cell markers (CD133 and CD44), were detected by a colorimetric DNMT activity/inhibition assay kit, quantitative real-time reverse transcription-polymerase chain reaction, sphere and colony formation assays, and immunoblot, respectively. Knockdown and overexpression of DNMT1 by transfection with shRNA and cDNA, respectively, were performed to explore the mechanism for action of CAS (0, 10, 30, and 100 nmol/L).@*RESULTS@#DNMT1 activity was increased in CCSLCs compared with HeLa and CaSki cells (P<0.05). In addition, HeLa-derived CCSLCs transfected with DNMT1 shRNA showed reduced sphere and colony formation abilities, and lower CD133, CD44, Nanog and Sox2 protein expressions (P<0.05). Conversely, overexpression of DNMT1 in HeLa cells exhibited the oppositive effects. Furthermore, CAS significantly reduced DNMT1 activity and transcription levels as well as stemness in HeLa-derived CCSLCs (P<0.05). Interestingly, DNMT1 knockdown enhanced the inhibitory effect of CAS on stemness. As expected, DNMT1 overexpression reversed the inhibitory effect of CAS on stemness in HeLa cells.@*CONCLUSION@#CAS effectively inhibits stemness in CCSLCs through suppression of DNMT1 activation, suggesting that CAS acts as a promising preventive and therapeutic candidate in cervical cancer.

Genomic analysis reveals genes affecting distinct phenotypes among different Chinese and western pig breeds.

The differences in artificial and natural selection have been some of the factors contributing to phenotypic diversity between Chinese and western pigs. Here, 830 individuals from western and Chinese pig breeds were genotyped using the reduced-representation genotyping method. First, we identified the selection signatures for different pig breeds. By comparing Chinese pigs and western pigs along the first principal component, the growth gene IGF1R; the immune genes IL1R1, IL1RL1, DUSP10, RAC3 and SWAP70; the meat quality-related gene SNORA50 and the olfactory gene OR1F1 were identified as candidate differentiated targets. Further, along a principal component separating Pudong White pigs from others, a potential causal gene for coat colour (EDNRB) was discovered. In addition, the divergent signatures evaluated by Fst within Chinese pig breeds found genes associated with the phenotypic features of coat colour, meat quality and feed efficiency among these indigenous pigs. Second, admixture and genomic introgression analysis were performed. Shan pigs have introgressed genes from Berkshire, Yorkshire and Hongdenglong pigs. The results of introgression mapping showed that this introgression conferred adaption to the local environment and coat colour of Chinese pigs and the superior productivity of western pigs.

Exendin-4 attenuates high glucose-induced endothelial progenitor cell dysfunction by regulating SIRTl/p53 signaling pathway / 中国药理学通报

Aim To investigate the effect of Exendin-4 high glucose and the function of silent information reg- on endothelial progenitor cells ( EPCs) induced by ulator 1 (SIRT1 ).Methods EPCs were isolated and cultured by density gradient centrifugation from peripheral blood of healthy volunteers.Different concentrations of Exendin-4( 12.5, 50, 100, 200 (xmol • L"1) induced EPCs were respectively performed by activity test to select the appropriate concentration.The optimal concentrations of Exendin-4 and high glucose (25 mmol • L 1) were incubated together for 72 h to detect the functional activities of EPCs.The capabilities of migration, adhension and tube formation of EPCs in vitro were detected respectively.The levels of LDH and MDA in EPCs were detected.The mRNA expressions of TNF-a, 1L-1 p and IL-6 in EPCs were measured by real-time fluorescent quantitative PCR ( RT-qPCR ).The protein expression of SIRT1 , P53 and Ac-P53 in EPCs were determined by Western blot.Results Ex- endin-4 could increase the viability of EPCs induced by j J high glucose in a dose-dependent manner, especially for 50 (xmol • L "1 (P <0.05 ).Hie results of Western blot showed that the protein expression of SIRT1 was significantly enhanced by 50 |xmol • L"' Exendin-4 treatment ( P < 0.05 ).Compared with high glucose group, Exenclin-4 significantly increased the migration, adhesion, tube formation of EPCs (P<0.05) and decreased the level of LDH and MDA ( P < 0.05 ).The mRNA expression of TNF-cx, lL-(3 and IL-6 in EPCs also decreased (P < 0.05).However, the protective effects of Exendin-4 could he significantly blocked by SIRT1 inhibitor ( EX-527) (P<0.05).In addition, the S1HT1 agonist ( SHT1720 ) could also improve the dysfunction of EPCs induced by high glucose ( P < 0.05).Conclusions Exendin-4 can improve the viability of human EPCs, restore the EPCs normal function, reduce high glucose-induced oxidative damage, and reduce the releases of inflammatory cvtokines un- j j der high glucose condition, which may be related to the regulation of S1HT1/P53 signaling pathway.

Pathological characteristics and clinical prognosis of nodular sclerosis grade 2 of classic Hodgkin's lymphoma / 中华肿瘤杂志

Objective: To investigate the pathological characteristics and clinical prognosis of nodular sclerosis grade 2 of classic Hodgkin's lymphoma (cHL-NS2) in our cancer center. Methods: A retrospective collection of 23 cases of cHL-NS2 admitted in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from July 2008 to April 2019 was performed. Fifty-five cases of nodular sclerosis grade 1 of classical Hodgkin's lymphoma (cHL-NS1) during the same period were selected as control group. Survival curves were plotted using the Kaplan-Meier method, and Cox regression model was used to analyze the influencing factors for survival. Results: The median age of 23 cases of cHL-NS2 was 30 years old. Five cases had extra nodal invasion, and 19 cases were Ⅰ-Ⅱ stage based on Ann Arbor system. The pathological morphology of cHL-NS2 showed that the lymph node structure was completely destroyed and was divided into nodules by thick collagen. The tumor cells in the nodules were abundant and proliferated in sheets. The boundaries between the tumor cells were not clear. The incidence of tumor necrosis in cHL-NS2 was 43.5% (10/23), which was significantly higher than 18.2% (10/55) in cHL-NS1 (P=0.040). The 3-year progression-free survival (PFS) rate of patients in the cHL-NS2 group was 58.1%, which was significantly lower than 89.7% in the cHL-NS1 group (P=0.002). In all of 78 cases, the 3-year PFS rate of patients who did not obtain complete response (CR) was 67.1%, which was significantly lower than 92.2% in patients who achieved CR (P=0.030). Multivariate Cox regression analysis demonstrated that both cHL-NS2 and failure to obtain CR by first-line treatment were independent indicators for short PFS time (P<0.05). Conclusions: In cHL-NS2, the morphology of tumor cells are diverse, and tumor necrosis can be easily found. Under the current first-line treatments of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), cHL-NS2 is an independent indicator for worse PFS.

Metal artifact reduction through MVCBCT and kVCT in radiotherapy.

This study proposes a new method for removal of metal artifacts from megavoltage cone beam computed tomography (MVCBCT) and kilovoltage CT (kVCT) images. Both images were combined to obtain prior image, which was forward projected to obtain surrogate data and replace metal trace in the uncorrected kVCT image. The corrected image was then reconstructed through filtered back projection. A similar radiotherapy plan was designed using the theoretical CT image, the uncorrected kVCT image, and the corrected image. The corrected images removed most metal artifacts, and the CT values were accurate. The corrected image also distinguished the hollow circular hole at the center of the metal. The uncorrected kVCT image did not display the internal structure of the metal, and the hole was misclassified as metal portion. Dose distribution calculated based on the corrected image was similar to that based on the theoretical CT image. The calculated dose distribution also evidently differed between the uncorrected kVCT image and the theoretical CT image. The use of the combined kVCT and MVCBCT to obtain the prior image can distinctly improve the quality of CT images containing large metal implants.

Enhancement of docosahexaenoic acid production by low-energy ion implantation coupled with screening method based on Sudan black B staining in Schizochytrium sp.

Schizochytrium sp. is a hopeful docosahexaenoic acid (DHA) producing candidate due to its rapid growth rate and high DHA proportion in total lipid content. In this study, low-energy ion implantation was applied to Schizochytrium sp. to induce high DHA-producing mutants. Screening these mutants by Sudan black B staining, a mutant strain S1 which showed a 61% improvement in DHA production than that of the parent strain was successfully selected. Subsequently, parameters of DHA production of mutant strain S1 were optimized in a 500-mL Erlenmeyer flask. Under the optimum fermentation conditions, the production of DHA and the percentage of DHA in total lipid of mutant strain S1 were 6.52g/L and 46.2%, respectively. This study provides an effective breeding strategy for improved DHA production of Schizochytrium sp. through combination of the novel mutagenesis technology, the effective screening method and fermentation optimization.

Role and treatment of ARIDIA in mutant tumors / 中国药理学通报

ARIDI A encodes a non-catalytic subunit of SWI/SNF chromosome remodeling complex BAF. Cancer genome sequencing data based on next-generation sequencing techniques have shown that ARIDIA is frequently mutated in a variety of cancers, up to 20% in some cancer types. A growing body of evidence shows that ARIDIA, as a tumor suppressor gene, affects the occurrence and development of cancers. ARIDIA plays an important role in cell cycle, DNA replication, DNA repair and transcriptional regulation, which might contribute to tumor formation, proliferation and migration. This review article mainly describes the research progress on ARIDIA in pan-cancer, as well as potential therapeutics, hoping to provide new ideas for the diagnosis and treatment of tumors.

Effect of Exendin-4 on endothelial progenitor cell function and AKT/eNOS signaling pathway in a mouse model of type 1 diabetes / 中国药理学通报

Aim To investigate the effect of Exendin4 on proliferation, migration, adhesion and senescence of endothelial progenitor cells (EPCs) in type I diabetic mice and its possible mechanism. Methods EPCs from 6-month diabetic mice were isolated and cultured by density gradient centrifugation. Cells were treated with different concentrations of Exendin-4 (1, 5, 10, 25 μmol · L

Application of PD-L1, PD-L2, CD30, CD23 and BCL-6 in Diagnosis and Prognostic Evaluation of Primary Mediastinal Large B-cell Lymphoma / 肿瘤防治研究

Objective To explore the application value of treatment-related markers PD-L1, PD-L2, CD30, CD23, BCL-2, BCL-6, MUM1 and GATA3 in the diagnosis and prognostic evaluation of primary mediastinal B-cell lymphoma(PMBL). Methods A retrospective study was conducted on 34 patients diagnosed with PMBL, and 31 patients with DLBCL-NOS which was not primary in the mediastinum were taken as control group. The expressions of 8 proteins were detected by IHC staining. Results The median percentages of tumor cells with PD-L1, PD-L2 and CD30 expression in PMBL group were 70% (30%, 90%), 25% (0, 70%) and 17.5% (0, 60%) respectively, which were significantly higher than those in the DLBCL-NOS group (P < 0.05). The positive rates of CD30 and CD23 in PMBL group were 61.76% (21/34) and 76.47% (26/34) respectively, significantly different with those in the DLBCL-NOS group (P=0.000). The survival curve of PMBL patients with CD30 or BCL-6 expression showed a trend of poor prognosis, despite the P value was > 0.05. Conclusion The high expression levels of PD-L1, PD-L2 and CD30 in PMBL are helpful to accurately identify more patients who may respond to immune or targeted therapy. Immunohistochemical staining of PD-L1, PD-L2, CD30 and CD23 is helpful for the differential diagnosis of PMBL and DLBCL-NOS. As candidate prognostic indicators of PMBL, CD30 and BCL-6 should be further studied in a larger number of samples.