Anomalous staged hot-electron acceleration by two-plasmon decay instability in magnetized plasmas.

We present a staged hot-electron acceleration mechanism of the two-plasmon decay (TPD) instability in the transverse magnetic field under the parameters relevant to inertial confinement fusion experiments. After being accelerated by the forward electron plasma wave (FEPW) of TPD, the hot-electrons can be anomalously accelerated again by the backward electron plasma wave (BEPW) of TPD and then obtain higher energy. Moreover, the surfatron acceleration mechanism of TPD in the magnetic field is also confirmed, the electrons trapped by the TPD daughter EPWs are accelerated in the direction along the wave front. Interestingly, the velocity of electrons accelerated by surfing from the FEPW is quite easily close to the BEPW phase velocity, which markedly enhances the efficiency of the staged acceleration. The coexistence of these two acceleration mechanisms leads to a significant increase of energetic electrons generated by TPD in the magnetic field. Meanwhile the EPWs are dissipated, TPD instability is effectively suppressed, and the laser transmission increases.

Kinetic model and Vlasov simulation verification of two-ion decay instability.

A kinetic theory is developed to describe the longitudinal decay of two-ion decay (TID): The pump ion-acoustic wave (IAW) decays into two daughter IAWs with a longer wavelength. The instability growth rate and threshold are given by the theory. Both the simulations of full kinetic Vlasov and hybrid Vlasov (kinetic ions and Boltzmann electrons) are employed to verify the theory and have a high quantitative agreement with the theory for 8≤ZT_{e}/T_{i}≤15, where Z is the ion charge number and T_{i}(T_{e}) is the ion (electron) temperature. The kinetic model developed here solves a long-standing problem that the simple fluid theory underestimates growth rate by a factor of 2∼3. Also, a reasonable explanation is given to the typical characteristics of TID that the dependence curves of subharmonic growth rate γ and wave number k.

[Application study of stool-based methylated SDC2 test in the screening of colorectal neoplasms for physical examination population].

Objective: To investigate the value of stool-based methylated SDC2 test in physical examination population for the screening of colorectal neoplasms. Methods: Using the prospective cohort study method, from December 2020 to November 2021, 2 107 participants from the First People's Hospital of Xiushui County, Jiangxi Province were enrolled, consisted of 1 012 males and 1 094 females, aged 20-90 years with the median age of 49 years old. Fresh stool samples were collected and SDC2 DNA methylation tests were carried out as the primary screening method. The participants with positive results were recommended to undergo colonoscopy, and those who were negative were followed up by telephone. The positive rate of screening, the compliance of colonoscopy, and the detection of colorectal lesions were analyzed by chi-square test. Combined the follow-up results of negative subjects, the value of SDC2 DNA methylation test for the screening of colorectal neoplasms was evaluated. Results: Among the 2 107 participants, 2 106 completed the SDC2 methylation test. 113 participants (5.4%) were positive. The positive rate of primary screening increased with age significantly (χ2=32.135, P<0.001). Out of 113 cases, 72 (63.7%) underwent colonoscopy examinations. Finally, 3 (4.2%) cases of colorectal cancer, 12 (16.7%) cases of advanced adenoma, 31 (43.1%) cases of non-advanced adenoma, and 16 (22.2%) cases of non-adenomatous polyp were detected. The positive predictive value (PPV) of stool-based SDC2 DNA methylation test for intestinal lesions and colorectal neoplasms were 86.1% and 63.9%, respectively. Among the 1 374 follow-up participants, the negative predictive value (NPV) of this test for intestinal lesions and colorectal neoplasms were 97.7% and 99.4%, respectively. Conclusion: Primary stool-based SDC2 DNA methylation test and subsequent colonoscopy examination can effectively find colorectal neoplasms. This strategy may be a potential tool for the screening of colorectal neoplasms in general risk population.

[Clinical application of multi-electrode synchronous radiofrequency ablation via switching controller for treating large hepatocellular carcinoma].

Objective: To explore the preliminary clinical efficacy and safety of multi-electrode synchronous radiofrequency ablation via switching controller for treating large hepatocellular carcinoma. Methods: A total of 20 patients with large hepatocellular carcinoma from minimally invasive Interventional department of Sun Yat-sen University Cancer Center were enrolled in this retrospective study from December 2013 to December 2014.The procedures were conducted with multi-electrode synchronous radiofrequency ablation via switching controller under CT guidance.The necrosis rate of tumor was assessed by the following imaging examination.The single factor analysis of variance (ANOVA) was employed to compare the total bilirubin, albumin, renal function, blood coagulation function before and after ablation, to evaluate the safety of treatment. Result: Twenty patients with a total of 31 lesions accepted 23 times ablation procedures using multi-electrode synchronous radiofrequency ablation via switching controller.The recent evaluation after treatment was as followed: complete necrosis rate 51.6% (16/31), nearly complete necrosis rate 22.6% (7/31), partial necrosis rate 9.7% (3/31), treatment effectiveness rate (necrosis rate > 50%) 83.9%.The necrosis rate which was less than half volume of the tumor was only seen in 5 cases with huge hepatocellular carcinoma (16.1%). No dead cases appeared after ablation procedures.The patients' total bilirubin elevated moderately after ablation procedures and reversed to normal level after liver function protection treatment.There were no statistical differences of renal function and blood coagulation function before and after ablation.After ablation procedures, 5 cases (21.7%, 5/23) appeared fever, 6 cases (26.1%) with vomiting, only 3 cases (13.0%, 3/23) with moderately severe pain in 3 days after ablation and remitted after taking oral analgesics in one week. Conclusion: The clinical efficacy of multi-electrode synchronous radiofrequency ablation via switching controller for large hepatocellular carcinoma is satisfactory with guaranteed security, which can be a choice for treating large hepatocellular carcinoma.

Leptin promotes apoptosis and inhibits autophagy of chondrocytes through upregulating lysyl oxidase-like 3 during osteoarthritis pathogenesis.

OBJECTIVE: Leptin has been found highly expressed in human osteoarthritis. We aimed to explore the possible effects and mechanisms of leptin on the apoptosis and autophagy of chondrocytes during osteoarthritis pathogenesis. METHODS: Gene expression profile from osteoarthritis affected and preserved cartilage were downloaded from NCBI's Gene Expression Omnibus database (GSE57218). Lysyl oxidase-like 3 (LOXL3) mRNA expression in cartilage tissues and leptin concentration in joint synovial fluid (SF) was measured in samples from 45 osteoarthritis patients and 25 healthy donors by real-time PCR and radioimmunoassay, respectively. Rat osteoarthritis model was induced by anterior cruciate ligament transection (ACLT). The expression of apoptosis regulators and autophagy markers were detected by Western blot. Cell survival and cell apoptosis were identified by CCK-8 and flow cytometry, respectively. RESULTS: Re-analysis on GSE57218 indicated that LOXL3 mRNA was upregulated in osteoarthritis affected cartilage. LOXL3 mRNA was upregulated in osteoarthritis patients, which was positively correlated with SF leptin concentration. Similar results were obtained in rat osteoarthritis model. Moreover, ACLT surgery led to a significant increase in the protein levels of cleaved caspase 3, and a notable decrease in the protein levels of Bcl-2, LC3 II/LC3 I and Beclin1. Silencing of LOXL3 in ACLT and leptin treated primary chondrocytes significantly inhibited cell apoptosis, and promoted cell proliferation and autophagy. Moreover, overexpression of LOXL3 remarkably inhibited autophagy of chondrocytes via activating mTORC1. CONCLUSIONS: LOXL3, a downstream of leptin, stimulated the apoptosis, but inhibited the autophagy of chondrocytes. LOXL3 is a potential therapy target for osteoarthritis.

Human dCTP pyrophosphatase 1 promotes breast cancer cell growth and stemness through the modulation on 5-methyl-dCTP metabolism and global hypomethylation.

Human DCTPP1 (dCTP pyrophosphatase 1), also known as XTP3-transactivated protein A, belongs to MazG-like nucleoside triphosphate pyrophosphatase (NTP-PPase) superfamily. Being a newly identified pyrophosphatase, its relevance to tumorigenesis and the mechanisms are not well investigated. In the present study, we have confirmed our previous study that DCTPP1 was significantly hyperexpressed in breast cancer and further demonstrated its strong association with tumor progression and poor prognosis in breast cancer. Knockdown of DCTPP1 in breast cancer cell line MCF-7 cells remarkably retarded proliferation and colony formation in vitro. The capacity of mammosphere formation of MCF-7 was suppressed with the silence of DCTPP1, which was consistent with the enhanced mammosphere-forming ability in DCTPP1-overexpressed MDA-MB-231 cells. To further dissect the mechanisms of DCTPP1 in promoting tumor cell growth and stemness maintenance, its biochemical properties and biological functions were investigated. DCTPP1 displayed bioactive form with tetrameric structure similar to other MazG domain-containing pyrophosphatases based on structure simulation. A substrate preference for dCTP and its methylated or halogen-modified derivatives over the other canonical (deoxy-) NTPs was demonstrated from enzymatic assay. This substrate preference was also proved in breast cancer cells that the intracellular 5-methyl-dCTP level increased in DCTPP1-deficient MCF-7 cells but decreased in DCTPP1-overexpressed MDA-MB-231 cells. Moreover, global methylation level was elevated in DCTPP1-knockdown MCF-7 cells or mammosphere-forming MCF-7 cells but decreased significantly in DCTPP1-overexpressed MDA-MB-231 cells and its mammospheres. Our results thus indicated that human DCTPP1 was capable of modulating the concentration of intracellular 5-methyl-dCTP. This in turn affected global methylation, contributing to a known phenomenon of hypomethylation related to the cancer cell growth and stemness maintenance. Our current investigations point to the pathological functions of DCTPP1 overexpression in breast cancer cells with aberrant dCTP metabolism and epigenetic modification.

Prognostic significance of cyclinD1 amplification and the co-alteration of cyclinD1/pRb/ppRb in patients with esophageal squamous cell carcinoma.

CyclinD1/pRb/ppRb is one of the most important pathways regulating the cell cycle, and related with the development of many cancers. However, the co-alteration of CyclinD1/pRb/ppRb in esophageal squamous cell carcinomas is less understood. This study aims to analyze the combined prognostic significance of cyclinD1 (CCND1) DNA amplification and the co-alteration of CCND1/pRb/ppRB in patients with esophageal squamous cell carcinoma. CCND1 DNA amplification and the protein expression of CCND1, pRb, and ppRb on 100 tumor specimens and 11 normal tissues were detected using real-time quantitative reverse transcription polymerase chain reaction and immunohistochemistry, respectively. Their prognosis significance was analyzed by Kaplan-Meier method. We found that 41% of the patients had CCND1 DNA amplification, which had a short survival time compared with the patients without CCND1 amplification (25.63 months vs. not reached, P=0.007). The patients with the co-alternation of CCND1(+) /pRb(-) /ppRb(+) protein expression levels have a poorer overall survival than the others (11.4 vs. 43.4 months, P=0.001). Cox regression analysis showed that the co-alternation of CCND1/pRb/ppRb and CyclinD1 amplification were the two most independent prognosis factors of patients with esophageal cancer. These findings suggested that CCND1 amplification and co-alternation of CCND1(+) /pRb(-) /ppRb(+) may play a crucial role in the prognostic evaluation of patients with esophageal cancer, and the patients with CCND1(+) /pRb(-) /ppRb(+) have the worst prognosis in all the patients. The results also indicated that the patients with CCND1 amplification or co-alternation of CyclinD1(+) /pRb(-) /ppRb(+) might be the preponderant people for therapy targeting the CCND1/pRb/ppRb pathway in the future.

Development of a foot scanner for assessing the mechanical properties of plantar soft tissues under different bodyweight loading in standing.

Mechanical properties of plantar soft tissues are important characteristics of the foot and are prone to being affected by foot pathologies such as diabetes. Therefore, it is of great importance to measure the mechanical properties of plantar soft tissues in vivo. However, such measurement in previous studies is mostly conducted in foot without loading and there is a paucity of instrument available which can assess the foot mechanical properties under a weight-loading status. In this study, a foot scanner incorporating a tissue ultrasound palpation (indentation) system (TUPS) which could assess the mechanical properties of plantar soft tissues under different body-weight loading was developed. The movement of the foot could also be monitored in real time during the indentation test to improve the test reliability. Preliminary tests were conducted on ten normal subjects at the heel region under various loading of the bodyweight. The results showed that the thickness decreased by 12.0% (from 13.83±2.52 mm to 12.10±1.95 mm) while the stiffness increased by 83.4% (from 40.0±20.7 kPa to 69.0±26.0 kPa) when the loading increased from 0% to 80% of the bodyweight (both p<0.001, repeated measure one-way ANOVA). Therefore, our system has been demonstrated to be useful in studying the loading dependence of mechanical properties of plantar soft tissues. Potential applications of the system in clinical studies for characterization and monitoring of foot pathologies such as ageing and diabetes are discussed at the end of this note.

Construction of the HBV S-ecdCD40L fusion gene and effects of HBV S-ecdCD40L modification on function of dendritic cells.

We examined the effect of dendritic cells engineered to express an HBV S antigen CD40L fusion gene (HBV S-ecdCD40L). The DNA of HBV S gene and the cDNA of the extracellular domain of human CD40 ligand were linked by cloning. Peripheral blood mononuclear cells (PBMC) from healthy adults were incubated and induced into dendritic cells (DC) in presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-4(IL-4). The DCs were transfected the novel construct, and the impact of the expressed clone assessed. We find that, compared with control groups, modification of DCs with HBV S-ecdCD40L fusion gene resulted in the activation of DCs with upregulated expression of immunologically important cell surface molecules (CD80, CD86 and HLA-DR) and proinflammatory cytokines (IL-12). The DCs modified with HBV S-ecdCD40L are able to stimulate enhanced allogeneic T-cell proliferation in vitro. Thus, the fusion gene HBV S-ecdCD40L can promote DC's activation and enhance its function and may prove to be the foundation for a new type of hepatitis B vaccine.

Evidence for the absence of mutations at GJB3, GJB4 and LOR in progressive symmetrical erythrokeratodermia.

BACKGROUND: Progressive symmetrical erythrokeratodermia (PSEK) is a rare inherited cornification disorder characterized by symmetrical erythematous hyperkeratotic plaques. The genetic basis for PSEK is not clear. PSEK shares many clinical features with erythrokeratodermia variabilis (EKV), which is associated with mutations in genes coding for gap junction beta (GJB) 3 and 4. A mutation in the loricrin gene (LOR) was found in patients with PSEK, who were members of a family with Vohwinkel syndrome. It would therefore be of interest to determine if PSEK is also caused by mutations in these genes. AIM: To examine the mutation status of GJB3, GJB4 and LOR in patients with PSEK and in control subjects. METHODS: Genomic DNA samples from 25 patients with PSEK and 56 healthy controls were examined by sequencing analysis of the coding sequences of GJB3, GJB4 and LOR. RESULTS: There were no mutations found in any of these three genes. CONCLUSIONS: PSEK is a disorder distinct from EKV, and the true pathogenesis of PSEK remains unknown.

Fine mapping of the disseminated superficial porokeratosis locus to a 2.7 Mb region at 18p11.3.

Disseminated superficial porokeratosis (DSP) is an autosomal dominant epidermal keratinization disorder. The genetic basis for DSP has not been clearly elucidated. We previously mapped the locus for DSP to a large region (5.7 Mb) at 18p11.3 in a four-generation Chinese family with DSP, but no gene responsible for porokeratosis has been identified to date. To narrow the critical region for DSP, thereby facilitating the identification of this disease gene and possibly leading to an understanding of the pathogenesis of porokeratosis, genotyping was performed on the same Chinese family with DSP using nine heterozygous single-nucleotide polymorphism markers at 18p11.3. We found the locus of DSP to be located within a 2.7 Mb region between markers rs58085394 and rs238533. Our study provides a map location for isolation of a gene causing DSP.

Nanofibrous scaffold engineering using electrospinning.

Scaffold plays a critical role in tissue engineering where it provides necessary structural support for the cells to accommodate and to guide their growth in the three dimensional space into a specific tissue. Therefore, engineering scaffolds favorable for cell/tissue growth is of great importance and a pre-requisite for scaffold-based tissue engineering. Electrospinning is a versatile method that has been recently adapted in engineering nano-fibrous scaffolds that mimic the structural features of biological extracellular matrix (ECM). It offers many advantages over conventional scaffold methodologies, for example, capable of producing ultra-fine fibers with high porosity, high spatial orientation, high aspect ratio, and high surface area, which are highly required for the initial cell attachment, tissue formation, and continued function. Considering these astonishing merits, this article emphasis on nano-fibrous scaffold engineering by electrospinning.

Characterization of the surface biocompatibility of the electrospun PCL-collagen nanofibers using fibroblasts.

The effect of nanofiber surface coatings on the cell's proliferation behavior was studied. Individually collagen-coated poly(epsilon-caprolactone) (PCL) nanofibers (i.e., Collagen-r-PCL in the form of a core-shell structure) were prepared by a coaxial electrospinning technique. A roughly collagen-coated PCL nanofibrous matrix was also prepared by soaking the PCL matrix in a 10 mg/mL collagen solution overnight. These two types of coated nanofibers were then used to investigate differences in biological responses in terms of proliferation and cell morphology of human dermal fibroblasts (HDF). It was found that coatings of collagen on PCL nanofibrous matrix definitely favored cells proliferation, and the efficiency is coating means dependent. As compared to PCL, the HDF density on the Collagen-r-PCL nanofiber membrane almost increased linearly by 19.5% (2 days), 22.9% (4 days), and 31.8% (6 days). In contrast, the roughly collagen-coated PCL increased only by 5.5% (2 days), 11.0% (4 days), and 21.0% (6 days). SEM observation indicated that the Collagen-r-PCL nanofibers encouraged cell migration inside the scaffolds. These findings suggest that the Collagen-r-PCL nanofibers can be used as novel functional biomimetic nanofibers toward achieving excellent integration between cells and scaffolds for tissue engineering applications.

[Comparison of effects of 5 and 20 Hz magnetic field on cerebral ischemia in rats].

OBJECTIVE: To compare the effects of 5 Hz and 20 Hz magnetic field on cerebral ischemia in rats. METHOD: After cerebral ischemia was produced by ligation of the left general carotid artery, rats were stimulated by magnetic fields of 5 Hz and 20 Hz respectively and pathological changes in neurocytes were observed. RESULT: (1) Different pathological changes were observed in different cells; (2) The extent of damage of pyramidal cells was milder in 5 Hz magnetic field groups than those in the control group, and the effect was not remarkable in the 20 Hz group; (3) The effect on astroglia was worse in 5 Hz group than that in control and 20 Hz group. CONCLUSION: Magnetic field stimulation influences cerebral ischemic reaction with frequency-dependency.

[c-fos expression in rat's vestibular nucleus under eccentric rotational stimulation].

OBJECTIVE: To investigate the c-fos expression in rat's vestibular nucleus under eccentric rotational stimulation and the effects of anti-motion sickness drug (PAPM) on this expression. METHOD: 19 SD rats were divided into three groups: A, B and C. A received as control. B was stimulated by eccentric rotation for 60 minutes. C received injection of PAPM through cavun abdominis 45 min before eccentric rotation. Immunohistochemical method and computerized image analysis were used to map locations of c-fos protein appeared in four vestibular nucleus and to count the masculine cells. RESULT: c-fos protein appeared in four vestibular nucleus areas after stimulation, and PAPM had no influence on this expression. CONCLUSION: It suggests that c-fos expression in vestibular nucleus is one of the important way in which vestibular nervous system reacts to outside stimulation and this expression has no direct relationship with the generation and development of motion sickness.

Antidiabetic effect of Oenanthe javanica flavone.

AIM: To study the antidiabetic effect of Oenanthe javanica flavone (OjF). METHODS: Mice were injected i.v. with alloxan 90 mg.kg-1 to induce diabetes. Blood glucose, serum lipid, and pancreatic amylase were determined with Automatic Biochemistry Analysor. Serum insulin was determined by radioimmunoassay. The pancreas and islets were examined under microscope. RESULTS: OjF 200 mg.kg-1 reduced the blood glucose in normal mice from 0.5 to 6 h after a single administration ig. OjF 200 and 400 mg.kg-1 ig daily for 10 d decreased the blood glucose in alloxan-induced hyperglycemic mice (P < 0.05, P < 0.01). OjF promoted the release of insulin both in normal and in diabetic mice. OjF decreased serum triglyceride and raised the lowered pancreatic amylases in diabetic mice (P < 0.01, P < 0.01). The islet-injured changes of OjF-treated group were similar to those of control in histology examination, but to a lesser degree. CONCLUSION: OjF possessed the hypoglycemic and hypotriglyceride actions, mainly concerned with promoting release of insulin from B-cells in islets of langerhans.

Prolactin and prolactin receptors in the lacrimal gland.

Light and electron microscopic immunocytochemistry, in situ hybridization and Dot Blot analysis revealed intracellular localization of prolactin-like molecules and prolactin mRNA in epithelial cells of the lacrimal glands of rabbits. There was also positive immunostaining for prolactin receptors on acinar cells and some interstitial cells. On Western blots of homogenates of whole lacrimal gland, isolated lacrimal acinar cells, isolated lacrimal interstitial cells and peripheral blood lymphocytes, prolactin antibody consistently labeled protein bands migrating at approximately 36 and 50 kD. These data confirm that lacrimal gland acinar cells produce endogenous prolactin-like molecules, but also express prolactin receptors. Since prolactin immunoreactivity has been detected in tear fluid and we found no accumulations of immunogold label in endocytic or transport vesicles, we hypothesize that the prolactin-like molecules in tear fluid originate primarily from synthesis within the acinar cells. We hypothesize further that prolactin from pituitary and other non-acinar cell origin has a modulating influence on acinar cell activity as well as immune function in the lacrimal gland, and that some of the prolactin-like molecules produced by the acinar cells contribute to these functions by autocrine/paracrine mechanisms.