Exploring the role of histone deacetylase and histone deacetylase inhibitors in the context of multiple myeloma: mechanisms, therapeutic implications, and future perspectives.

Histone deacetylase inhibitors (HDACis) are a significant category of pharmaceuticals that have developed in the past two decades to treat multiple myeloma. Four drugs in this category have received approval from the U.S. Food and Drug Administration (FDA) for use: Panobinonstat (though canceled by the FDA in 2022), Vorinostat, Belinostat and Romidepsin. The efficacy of this group of drugs is attributed to the disruption of many processes involved in tumor growth through the inhibition of histone deacetylase, and this mode of action leads to significant anti-multiple myeloma (MM) activity. In MM, inhibition of histone deacetylase has many downstream consequences, including suppression of NF-κB signaling and HSP90, upregulation of cell cycle regulators (p21, p53), and downregulation of antiapoptotic proteins including Bcl-2. Furthermore, HDACis have a variety of direct and indirect oxidative effects on cellular DNA. HDAC inhibitors enhance normal immune function, thereby decreasing the proliferation of malignant plasma cells and promoting autophagy. The various biological effects of inhibiting histone deacetylase have a combined or additional impact when used alongside other chemotherapeutic and targeted drugs for multiple myeloma. This helps to decrease resistance to treatment. Combination treatment regimens that include HDACis have become an essential part of the therapy for multiple myeloma. These regimens incorporate drugs from other important classes of anti-myeloma agents, such as immunomodulatory drugs (IMiDs), conventional chemotherapy, monoclonal antibodies, and proteasome inhibitors. This review provides a comprehensive evaluation of the clinical efficacy and safety data pertaining to the currently approved histone deacetylase inhibitors, as well as an explanation of the crucial function of histone deacetylase in multiple myeloma and the characteristics of the different histone deacetylase inhibitors. Moreover, it provides a concise overview of the most recent developments in the use of histone deacetylase inhibitors for treating multiple myeloma, as well as potential future uses in treatment.

The oncogenic and immunological roles of histidine triad nucleotide-binding protein 1 in human cancers and their experimental validation in the MCF-7 cell line.

Background: Histidine triad nucleotide binding protein 1 (HINT1) is a haplo-insufficient tumor suppressor gene that plays a significant role in cell proliferation and survival. However, to date, no systematic pan-cancer analysis has been conducted to explore its function in prognosis, and its oncogenic and immunological roles. We also analyzed the role of HINT1 in breast cancer (BC) progression in vitro. Methods: An analysis of the HINT1 expression pattern was performed using the TIMER database. The infiltration of immune cells into several cancer types was also studied using the Xena Shiny tool. To determine the relationship between stemness and the expression of HINT1 mRNA, the Spearman correlation test was used with the SangerBox tool. The correlation between HINT1 and functional states in various cancers was determined from the CancerSEA database. The potential role of HINT1 in BC oncogenesis was also investigated by Western blot and Annexin V/PI assays. Results: The Cancer Genome Atlas pan-cancer data analysis suggested that HINT1 was extensively altered in most tumor tissues but not in most adjacent normal tissues. A high expression of HINT1 was associated with the decreased infiltration of cluster of differentiation (CD)4+ T cells. Importantly, increased HINT1 expression was also associated with a large majority of tumors with high stemness and lower stromal, immune, and estimate scores. Further, the expression of HINT1 was significantly associated with the tumor mutational burden (TMB) and microsatellite instability (MSI) in certain tumor types. Finally, HINT1 overexpression was found to impair BC progression by promoting cell apoptosis. HINT1 upregulation also reduced the expression of microphthalmia transcription factor (MITF) and ß-catenin in BC Michigan Cancer Foundation-7 (MCF-7) cells, and the phosphorylation of protein kinase B (p-Akt). Conclusions: The present study showed that HINT1 plays an oncogenic role in various cancers and could also be used as a biomarker for BC.

Correlation between circulating tumor cells and different molecular biological characteristics in breast cancer patients.

Background: This study sought to detect the number of circulating tumor cells (CTCs) in breast cancer patients, and examine the relationship between CTCs and molecular biological characteristics. Methods: From June 2016 to June 2018, 150 female patients with invasive breast cancer detected by CTCs at the Department of Breast Surgery, Fudan University Cancer Hospital were enrolled in this study. The patients had an average age of 52.6±7.8 (range, 35-77) years. Routine pathological and immunohistochemical examinations were performed on tissues obtained during surgery. In this study, CTCs were detected using the immunomagnetic bead negative enrichment technique (i.e., the Cyttel technique). The measurement data are expressed by x ± s, and were compared by t-tests. A univariate analysis of variance was used to compare differences between groups. The count data are expressed as the absolute value, and the test χ2 or Fisher's exact test were used to compare differences. Results: There were 109 cases of positive CTC (≥3 CTCs/4 mL) (72.7%), and 41 cases of negative CTC (<3 CTCs/4 mL) (27.3%). There were no significant differences in terms of age and menopausal status between the two groups (P>0.05). There was no significant difference in the positive rate of CTC in T1, T2, and T3 and above patients (P>0.05). There was no significant difference in the CTC positive rate between ER positive and negative patients, PR positive and negative patients, and Ki-67 ≥14% and <14% patients (P>0.05). However, there was a statistical difference in the positive rate of CTC between human epidermal growth factor receptor 2 (HER-2) positive and negative patients (P<0.05). There was no significant difference in the CTC positive rate among patients with Luminal A type, B type, HER-2 overexpression type, and triple negative breast cancer (TNBC) (P>0.05). There was no significant difference in the positive rate of CTC among patients with invasive ductal carcinoma, invasive lobular carcinoma, and other types of invasive carcinoma (P>0.05). Conclusions: It can be concluded that there is a relationship between CTC and HER-2 expression, which has certain predictive value for patients with positive HER-2 expression, thus predicting poor prognosis.

Role of SLC39A6 in the development and progression of liver cancer.

Liver cancer is one of the most common malignant solid tumor types worldwide. The solute carrier (SLC)39A family is a main member of the SLC group of membrane transport proteins, which transfer zinc to the cytoplasm when cells are depleted of zinc; thus, it may provide a novel therapeutic target for human cancer. However, the prognostic value of SLC39A genes in patients with liver cancer has remained elusive. Therefore, the present study aimed to explore whether SLC39A family genes are associated with the survival rate of patients with liver cancer and to investigate the role of key genes of the SLC39A family in liver cancer. The mRNA expression of the SLC39A family in liver cancer was obtained from the UALCAN database. Survival curve analysis was performed to investigate the prognostic value of SLC39A family genes in the overall survival of patients with liver cancer. In addition to the bioinformatics analysis, SLC39A6 was knocked down in HepG2 and Hep3B cells to examine the effect on the proliferation, migration and invasion of liver cancer cells. The results suggested that SLC39A6 was significantly upregulated in liver cancer tissues compared with normal liver tissues. High expression of SLC39A6 was significantly associated with poor overall survival of patients with liver cancer. Furthermore, knockdown of SLC39A6 inhibited the proliferation, migration and invasion of liver cancer cells in vitro and in vivo. Collectively, the results of the present study suggested that SLC39A6 may be a promising prognostic biomarker for liver cancer and is associated with the proliferation, migration and invasion of liver cancer.

Use of targeted therapy and immunotherapy for the treatment of yolk sac tumors in extragonadal pelvic sites: two case reports.

We present the clinicopathologic features and treatments of two cases of extragonadal yolk sac tumor (EGYST) detected in young females, including one in the myometrium admitted in 2013 and another in the serosal layer of the anterior wall of uterus admitted in 2019. The following details were recorded: patient age, clinical presentation, tumor location, International Federation of Gynecology and Obstetrics (FIGO) stage (where applicable), histologic patterns including Schiller-Duval (SD) bodies, other germ cell or somatic components, immunoperoxidase results, treatment, and outcome. The patients were aged 18 and 32 years old, both displayed the clinical manifestation of pain in the lower abdomen, tumor sizes were 10 and 8 cm, respectively, and alpha-fetoprotein (AFP) was significantly increased (1,210-20,251.0 ng/mL). Both participants underwent surgery and typical SD bodies were observed in postoperative pathology. Immunohistochemistry (IHC) results indicated that they were AFP positive (+) and Sal-like protein 4 (SALL4) (+). Both patients received multi-line chemotherapy after surgery, and participant 2 received targeted therapy and immunotherapy. At 36 months after surgery, one patient died, and the other was still receiving treatment. The benefit of germ cell appropriate chemotherapy in somatically derived EGYST has not been fully elucidated. Our report first showed that it is possible to reduce the recurrence rate and improve the prognosis of patients with EGYST by adding targeted therapy and immunotherapy (bevacizumab + tislelizumab) to traditional chemotherapy regimens.

STK17B promotes the progression of ovarian cancer.

BACKGROUND: Protein kinase is increasingly receiving widespread attention because of its role in the tumor progression. Serine/threonine protein kinase (STK) is an important family involved in the development of a variety of cancers. Many studies have shown that serine/threonine kinase 17B (STK17B) is highly expressed in a variety of malignant tumors and participate in proliferation and metastasis. However, the exact function of STK17B remains uncertain in ovarian cancer. Our study aims to investigate whether STK17B plays a role in the occurrence and development of epithelial ovarian cancer. METHODS: We employed quantitative reverse transcription polymerase chain reaction to detect the relative expression of STK17B in ovarian cancer tissues. STK17B was down-regulated and up-regulated in ovarian cancer cell lines by small interfering RNA and overexpressed plasmid, respectively. The effects of STK17B on proliferation, invasion and migration of ovarian cancer cells in vitro were analyzed by CCK-8 test, Transwell test, scratch test and EDU test. The tumorigenicity of subcutaneous xenograft tumor in nude mice to study the role of STK17B in tumorigenesis in vivo. Western Blotting analysis revealed that STK17B and EMT. RESULTS: STK17B expression was significantly increased in ovarian cancer tissues. The STK17B silencing suppressed cell progression, while the overexpression of STK17B promoted progression in vivo or in vitro. Western bolt showed that STK17B increased the invasion and migration of ovarian cancer cell by promoting the EMT process. CONCLUSIONS: STK17B was highly expressed in epithelial ovarian cancer tissues and increased the proliferation, invasion and migration of ovarian cancer cells by promoting EMT process.

Impact of surgeon work duration prior to distal pancreatectomy on perioperative outcomes: a propensity score matching analysis.

BACKGROUND: Surgeons are likely to get progressively fatigued during the course of a normal workday. The objective of this study was to evaluate the impact of surgeon work duration prior to performing distal pancreatectomy (DP) on the perioperative outcome, especially frequency of grade II or higher grade postoperative complications. METHODS: Patients undergoing DP for all causes were divided into two groups according to surgeon work hours prior to performing DP: group A (less than 5 h) and group B (5-10 h). Propensity score matching (PSM) analysis (1:1) were performed to balance the baseline characteristics between the two groups. Intraoperative complications were compared between the two groups. Postoperative complications and their severity were followed up for 60 days and mortality for 90 days. The study was powdered to identify a 15% difference in the incidence of grade II or higher grade complications. RESULTS: By using PSM analysis, the patients in group A (N = 202) and group B (N = 202) were well matched regarding demographics, comorbidities, operative technique, pancreatic texture and pathology. There was no significant difference in the incidence of grade II or higher grade complications between the two groups. There was no difference in clinically relevant postoperative pancreatic fistula, percutaneous drainage, readmission, reoperation, or morality. Group B was associated with a higher incidence of intraoperative organ injury, which could be managed successfully during the operation. CONCLUSION: The retrospective study demonstrated that the surgeon work duration did not significantly affect the clinical outcome of DP.

Reducing LncRNA-5657 expression inhibits the brain inflammatory reaction in septic rats.

Our preliminary study found that the long noncoding RNA (LncRNA)-5657 can reduce the expression of inflammatory factors during inflammatory reactions in rat glial cells. However, the role played by LncRNA-5657 during septic brain injury remains unclear. In the present study, rat models of septic encephalopathy were established by cecal ligation and puncture, and then the rats were treated with a hippocampal injection small hairpin RNA (shRNA) against LncRNA-5657 (sh-LnCRNA-5657). The sh-LncRNA-5657 treatment reduced the level of neuronal degeneration and necrosis in the rat hippocampus, reduced the immunoreactivities of aquaporin 4, heparanase, and metallopeptidase-9, and lowered the level of tumor necrosis factor-alpha. Glial cells were pre-treated with sh-LncRNA-5657 and then treated with 1 µg/mL lipopolysaccharide. Sh-LncRNA-5657 transfection decreased the expression of LncRNA-5657 in lipopolysaccharide-treated glial cells and decreased the mRNA and protein levels of tumor necrosis factor-alpha, interleukin-1ß, and interleukin-6. These findings suggested that LncRNA-5657 expression can significantly reduce the inflammatory reaction during septic encephalopathy and induce protective effects against this disease. This study was approved by the Institutional Ethics Committee at the First Affiliated Hospital of Nanchang University of China (approval No. 2017-004) in 2017.

Comprehensive assessment of deceased donor kidneys with clinical characteristics, pre-implant biopsy histopathology and hypothermic mechanical perfusion parameters is highly predictive of delayed graft function.

Background: Due to the current high demand for transplant tissue, an increasing proportion of kidney donors are considered extended criteria donors, which results in a higher incidence of delayed graft function (DGF) in organ recipients. Therefore, it is important to fully investigate the risk factors of DGF, and establish a prediction system to assess donor kidney quality before transplantation.Methods: A total of 333 donation after cardiac death kidney transplant recipients were included in this retrospective study. Both univariate and multivariate analyses were used to analyze the risk factors of DGF occurrence. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of variables on DGF posttransplant.Results: The donor clinical scores, kidney histopathologic Remuzzi scores and hypothermic mechanical perfusion (HMP) parameters (flow and resistance index) were all correlated. 46 recipients developed DGF postoperatively, with an incidence of 13.8% (46/333). Multivariate logistic regression analysis of the kidney transplants revealed that the independent risk factors of DGF occurrence post-transplantation included donor score (OR = 1.12, 95% CI 1.06-1.19, p < 0.001), Remuzzi score (OR = 1.21, 95% CI 1.02-1.43, p = 0.029) and acute tubular injury (ATI) score (OR = 4.72, 95% CI 2.32-9.60, p < 0.001). Prediction of DGF with ROC curve showed that the area under the curve was increased to 0.89 when all variables (donor score, Remuzzi score, ATI score and HMP resistance index) were considered together.Conclusions: Combination of donor clinical information, kidney pre-implant histopathology and HMP parameters provide a more accurate prediction of DGF occurrence post-transplantation than any of the measures alone.

A novel robust adsorbent for efficient oil/water separation: Magnetic carbon nanospheres/graphene composite aerogel.

Recently, graphene aerogels (GAs) have attracted considerable research attention in oil/water separation owing to their remarkable properties. However, the serious stacking of graphene oxide nanosheets (GO) would lead to low adsorption capacity and poor recyclability. For the first time, with alkaline ammonium citrate as reducing agent and nitrogen source, the point-to-face contact between magnetic carbon nanospheres (MCNS) and graphene sheets was adopted to effectively inhibit the aggregation of graphene sheets. Nitrogen-doped magnetic carbon nanospheres/graphene composite aerogels (MCNS/NGA) were fabricated under weakly alkaline conditions by one-step hydrothermal in-situ electrostatic self-assembling strategy. The aerogels have low density, super-elasticity (up to 95 % compression), high specific surface area (787.92 m2 g-1) and good magnetic properties. Therefore, they exhibit adsorption capacity in the range of 187-537 g g-1 towards various organic solvents and oils, superior to most reported materials to date. In addition, thanks to their good mechanical properties, excellent thermal stability and flame retardancy, they can be regenerated by squeezing, distillation and combustion. More importantly, magnetic control technology can be adopted to realize oriented adsorption and facilitate recycling of organic solvents and oils in extreme environments.

Comparative iTRAQ proteomics revealed proteins associated with lobed fin regeneration in Bichirs.

BACKGROUND: Polypterus senegalus can fully regenerate its pectoral lobed fins, including a complex endoskeleton, with remarkable precision. However, despite the enormous potential of this species for use in medical research, its regeneration mechanisms remain largely unknown. METHODS: To identify the differentially expressed proteins (DEPs) during the early stages of lobed fin regeneration in P. senegalus, we performed a differential proteomic analysis using isobaric tag for relative and absolute quantitation (iTRAQ) approach based quantitative proteome from the pectoral lobed fins at 3 time points. Furthermore, we validated the changes in protein expression with multiple-reaction monitoring (MRM) analysis. RESULTS: The experiment yielded a total of 3177 proteins and 15,091 unique peptides including 1006 non-redundant (nr) DEPs. Of these, 592 were upregulated while 349 were downregulated after lobed fin amputation when compared to the original tissue. Bioinformatics analyses showed that the DEPs were mainly associated with Ribosome and RNA transport, metabolic, ECM-receptor interaction, Golgi and endoplasmic reticulum, DNA replication, and Regulation of actin cytoskeleton. CONCLUSIONS: To our knowledge, this is the first proteomic research to investigate alterations in protein levels and affected pathways in bichirs' lobe-fin/limb regeneration. In addition, our study demonstrated a highly dynamic regulation during lobed fin regeneration in P. senegalus. These results not only provide a comprehensive dataset on differentially expressed proteins during the early stages of lobe-fin/limb regeneration but also advance our understanding of the molecular mechanisms underlying lobe-fin/limb regeneration.

B-Cell Activating Factor Predicts Acute Rejection Risk in Kidney Transplant Recipients: A 6-Month Follow-Up Study.

B cell activating factor (BAFF) belonging to TNF family is a cytokine that enhances B-cell proliferation and differentiation. Recently, It has been suggested that BAFF might be a potential therapeutic target for treating autoimmune disease. However, the relationship between BAFF and allograft rejection is controversial, and the clinical significance of BAFF in predicting allograft rejection need to be further explored. We conducted 6-month follow-up study to confirm the hypothesis that BAFF might be a risk factor for predicting acute rejection in kidney transplant recipients. At the end of the study, a total of 155 kidney transplant recipients were recruited from October 2015 to October 2017, and classified into acute rejection group (n = 34) and stable renal function group (n = 121) according to their clinical course. We demonstrate that the serum BAFF levels when acute rejection occurred was significantly higher than that in the stable renal function group (2426.19 ± 892.19 vs. 988.17 ± 485.63 pg/mL, P < 0.05). BAFF expression was significantly enhanced in the membrane and cytoplasm of renal tubule epithelial cells in the transplant kidney tissue with acute rejection, and a positive correlation between BAFF and C4d expression was also observed (r = 0.880, P = 0.001). ROC analyses highlight the superiority of serum BAFF level before transplant over those on other post-transplant days in prediction of acute rejection episodes. The sensitivity, specificity and AUC (area under curve) were 83.3, 89.5, and 0.886%, respectively. Kaplan-Meier survival analysis showed that recipients with higher pretransplant BAFF levels had higher acute rejection incidence (P = 0.003). In conclusion, we have identified that BAFF levels are associated with the acute rejection and could be a promising biomarker to predict kidney transplant rejection risks.

Mitochondrial DNA plays an important role in lung injury induced by sepsis.

The effects and mechanisms of mitochondrial DNA (mtDNA) in the development of sepsis-induced lung injury is not well understood. In our present study, we studied the mtDNA effects in sepsis-induced lung injury model, in vitro and in vivo. Compared with the Normal group, the lung histopathological score, the number of positive apoptosis cell, wet/dry (W/D) ratio and TNF-α, IL-1ß, and IL-6 concentrations of lipopolysaccharides (LPSs) and mtDNA groups were significantly increased (P < 0.001, respectively). Meanwhile, the lung histopathological score, positive W/D ratio, number of apoptosis cell and tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6 concentrations of LPS + mtDNA and small interfering RNA (siRNA)-NC + LPS + mtDNA groups were significantly upregulated compared with those of LPS group (P < 0.05, respectively). However, the lung histopathological score, the number of positive apoptosis cell, W/D ratio and TNF-α, IL-1ß, and IL-6 concentrations were significantly improved within the toll-like receptor (TLR9)siRNA + LPS + mtDNA group compared with the LPS group (P < 0.01, respectively). The TLR9, MyD88, and NF-κB proteins or gene expressions of the LPS group and mtDNA group were significantly upregulated compared with those of Normal group by Western blot analysis or immunohistochemistry assay (P < 0.01, respectively), and the TLR9, MyD88, and NF-κB proteins or gene expressions of LPS + mtDNA and siRNA-NC + LPS + mtDNA groups were significantly enhanced compared with those of LPS group (P < 0.05, respectively). However, the TLR9, MyD88, and NF-κB proteins or gene expressions of TLR9siRNA + LPS + mtDNA group were significantly suppressed compared with those of the LPS group (P < 0.01, respectively). In conclusion, mtDNA could provoke lung injury induced by sepsis via regulation of TLR9/MyD88/NF-κB pathway in vitro and in vivo.

The diagnostic value of one step nucleic acid amplification (OSNA) in differentiating lymph node metastasis of tumors: A systematic review and meta-analysis.

BACKGROUND: The aim of this study was clarify the diagnostic accuracy of one step nucleic acid amplification (OSNA) for differentiating metastatic lymph nodes from non-metastatic ones in patients with tumors (not including breast cancer). METHODS: A systematic literature search for original diagnostic studies was performed in PubMed. Findings were pooled by using combined effect models and hierarchic summary receiver operating characteristic curve models. Meta-regression analysis and threshold effect evaluating were performed to explore the sources of heterogeneity affected classification accuracy. RESULTS: 19 studies (803 positive and 4594 negative lymph nodes) were analyzed, including 4 different tumor types (head and neck cancers, gastrointestinal cancers, lung cancer and gynecological malignancies). In the studies of head and neck cancers the pooled sensitivity, specificity and area under the curve (AUC) of the OSNA method were 0.85(0.79-0.89), 0.96(0.92-0.98) and 0.91 (0.88-0.93), respectively. Similarly, the corresponding values in the studies of gastrointestinal cancers were 0.90(0.85-0.94), 0.96(0.94-0.98) and 0.97 (0.96-0.99), respectively. Because of limited number of studies, the other two tumor types were inestimable in the subsequent meta-analyses. CONCLUSIONS: Pooled data suggest that the OSNA assay has a high diagnostic accuracy for the detection of lymph node metastases. For wide spread implementation, additional studies on other different types of tumors are warranted.

Cyprininae phylogeny revealed independent origins of the Tibetan Plateau endemic polyploid cyprinids and their diversifications related to the Neogene uplift of the plateau.

Origin and diversification of the Tibetan polyploid cyprinids (schizothoracins) may help us to explore relationships between diversification of the cyprinids and the Tibetan Plateau uplift. Cyprininae phylogeny was analyzed using mitochondrial and nuclear DNA sequences to trace origins of polyploidy and diversifications of schizothoracins. Ancestral states reconstruction for ploidy levels indicated that the Cyprininae was diploid origin and the schizothoracin clades tetraploid origins. There were two diversification rate shifts along with diversification of the cyprinine fishes in response to the Tibetan uplift. The unusual diversification shifts were located to branches subtending the clades of Tibetan polyploid cyprinids. Our analyses suggested that (i) phylogeny of Cyprininae recovered two independent origins of the Tibetan polyploidy schizothoracins; (ii) diversifications of the schizothoracins were closely related to the Neogene uplift of the Tibetan plateau in the following ways: the relatively ancient Late Oligocene-Middle Miocene adaptive radiation may be associated with the uplift of the southern Tibet and Himalaya; the Middle Miocene-Early Pleistocene lineage-specific diversification broadly coincident with major phase of the Neogene Tibetan uplift; and the most recent Pleistocene diversification shift in Schizothorax closely coincident with the successive Kunlun-Huanghe and Gonghe movements of the Tibetan uplift and the glaciation-induced climate oscillations on the plateau.

Multifunctional nitrogen-doped graphene nanoribbon aerogels for superior lithium storage and cell culture.

Nitrogen-doped graphene nanoribbon aerogels (N-GNRAs) are fabricated through the self-assembly of graphene oxide nanoribbons (GONRs) combined with a thermal annealing process. Amino-groups are grafted to the surface of graphene nanoribbons (GNRs) by an epoxy ring-opening reaction. High nitrogen doping level (7.6 atm% as confirmed by elemental analysis) is achieved during thermal treatment resulting from functionalization and the rich edge structures of GNRs. The three dimensional (3D) N-GNRAs feature a hierarchical porous structure. The quasi-one dimensional (1D) GNRs act as the building blocks for the construction of fishnet-like GNR sheets, which further create 3D frameworks with micrometer-scale pores. The edge effect of GNRs combined with nitrogen doping and porosity give rise to good electrical conductivity, superhydrophilic, highly compressible and low density GNRAs. As a result, a high capacity of 910 mA h g(-1) is achieved at a current density of 0.5 A g(-1) when they are tested as anode materials for lithium ion batteries. Further cell culture experiments with the GNRAs as human medulloblastoma DAOY cell scaffolds demonstrate their good biocompatibility, inferring potential applications in the biomedical field.

Phylogeny and polyploidy: resolving the classification of cyprinine fishes (Teleostei: Cypriniformes).

Cyprininae is the largest subfamily (>1300 species) of the family Cyprinidae and contains more polyploid species (∼400) than any other group of fishes. We examined the phylogenetic relationships of the Cyprininae based on extensive taxon, geographical, and genomic sampling of the taxa, using both mitochondrial and nuclear genes to address the phylogenetic challenges posed by polyploidy. Four datasets were analyzed in this study: two mitochondrial gene datasets (465 and 791 taxa, 5604bp), a mitogenome dataset (85 taxa, 14,771bp), and a cloned nuclear RAG1 dataset (97 taxa, 1497bp). Based on resulting trees, the subfamily Cyprininae was subdivided into 11 tribes: Probarbini (new; Probarbus+Catlocarpio), Labeonini Bleeker, 1859 (Labeo & allies), Torini Karaman, 1971 (Tor, Labeobarbus & allies), Smiliogastrini Bleeker, 1863 (Puntius, Enteromius & allies), Poropuntiini (Poropuntius & allies), Cyprinini Rafinesque, 1815 (Cyprinus & allies), Acrossocheilini (new; Acrossocheilus & allies), Spinibarbini (new; Spinibarbus), Schizothoracini McClelland, 1842 (Schizothorax & allies), Schizopygopsini Mirza, 1991 (Schizopygopsis & allies), and Barbini Bleeker, 1859 (Barbus & allies). Phylogenetic relationships within each tribe were discussed. Two or three distinct RAG1 lineages were identified for each of the following tribes Torini, Cyprinini, Spinibarbini, and Barbini, indicating their hybrid origin. The hexaploid African Labeobarbus & allies and Western Asian Capoeta are likely derived from two independent hybridization events between their respective maternal tetraploid ancestors and Cyprinion.

Increased intracellular adenosine triphosphate level as an index to predict acute rejection in kidney transplant recipients.

BACKGROUND: Peripheral blood CD4+ T cell adenosine triphosphate (ATP) release has been reported to be an adjunct tool to evaluate global cellular immune response in solid-organ transplant recipients. However, the correlation between the ATP level and rejection was controversial. The aim of this prospective clinical study was to explore the association between the intracellular ATP level and the occurrence, progression, and treatment of acute rejection (AR) episodes, determine the predicting value of intracellular ATP level for AR in kidney transplant (KT) recipients. PATIENTS AND METHODS: In the period of October 2011 to October 2012, 140 KT recipients were recruited and followed for six months after transplantation. Patients were categorized into stable group and AR group according to their clinical course. Whole blood samples were collected pretransplantation, and at 7, 14, 21, and 28days, and at 2, 3, 4, 5 and 6months post-transplantation. Additional blood samples were obtained from AR patients on the day AR occurred, on the day before and 3 and 7days after intravenous anti-rejection therapy started, and on the day when AR reversed. The intracellular ATP in CD4+ T cells was detected by ImmuKnow Immune Cell Function Assay according to the manufacturer's instruction. The absolute number of CD4+ T cells and the trough levels of tacrolimus and cyclosporine were also measured. RESULTS: The ATP level detected on the day AR occurred (627.07±149.85ng/ml) was obviously higher than that of the stable group (320.48±149.11ng/ml, P<0.05). ATP value decreased to 265.35±84.33ng/m at the end of anti-rejection therapy, which was obviously lower than that measured on the day before the anti-rejection therapy started (665.87±162.85ng/ml, P<0.05). ROC analysis revealed that increased intracellular adenosine triphosphate level showed better sensitivity and specificity than those obtained using single time point detection (89.5% vs 85.0%;95.0% vs 88.9%). The best cutoff value was 172.55ng/ml. A positive correlation between the intracellular ATP level and absolute CD4+ T cell number (r=0.656, P<0.001) was found in the patients with CD4+ T cell counts <200/µl.