Improving ranging performance of SiPM LiDAR in low SNR conditions through an echo processing method and laser pulse modulation.

Due to its numerous advantages such as high gain and low operating bias, the silicon photomultiplier (SiPM) holds great potential in LiDAR applications. However, it is more jittery at weak echoes and more sensitive to ambient light, making its ranging performance at low signal-to-noise ratios (SNRs) severely deteriorated. To enhance the ranging performance of SiPM LiDAR under low SNR, a novel echo processing method, to the best of our knowledge, was proposed based on the statistical property of SiPM responses and validated under relatively intensive sunlight (>50k l x) using a self-developed LiDAR system. At the same time, laser pulse width modulation and multi-pulse laser emission are used in ranging experiments to maximize the advantages of this method. It has shown that increasing the laser pulse width within a certain range can improve ranging performance, and that emitting multiple laser pulses improves ranging performance more significantly. Utilizing a three-pulse laser with a peak power of only 3.2 W, a target 122 m away was ranged with a precision of 6.53 cm with only five accumulations.

Effects of bamboo shoots (Phyllostachys edulis) dietary fibers prepared by different processes on the adsorption characteristics of polyphenols.

In this work, adopting bamboo shoots as raw materials, three kinds of bamboo shoots dietary fibers were prepared by physical, chemical, and enzymatic methods, termed BSPDF, BSCDF, and BSEDF, respectively, and then investigating their adsorption characteristics for polyphenols through soaked them in different concentrations and different types of polyphenol solutions. The results of the adsorption kinetics showed that the adsorption amounts of polyphenols significantly increased during the initial 30 s of soaking, and the subsequent adsorption rate became slower and slower achieving adsorption kinetics after 2 hr. Moreover, their adsorption isotherms met well with the Langmuir model, but differences in saturated adsorption capacity and adsorption rate. More impressively, the maximum adsorption capacities Qmax of them to polyphenols followed the order of catechin > phlorizin dihydrate > chlorogenic acid > gallic acid. In addition, BSPDF, BSCDF and BSEDF all could adsorb a large amount of free catechin with the saturated adsorption capacity of 15.77, 14.69 and 16.76 mg/g, respectively and which exhibited blue and green characteristic fluorescence emission signals in the presence of catechin. Therefore, compared with the other two methods, the enzymatic hydrolysis method retains the spatial network structure of the fibrils, has a larger surface area and porosity, retains the original bound phenol of fibrils, with stronger physiological activity and more potential applications. PRACTICAL APPLICATIONS: Polyphenols are easy to oxidize in vitro, and are easily affected by gastric acid and various enzymes in vivo, which reduce their physiological activity. However, dietary fibers can resist the destruction of various enzymes and acids in the gastrointestinal tract. It is increasingly being realized that dietary fibers play a very important role in adsorbing polyphenols into its network structure, which can achieve the purpose of protecting polyphenols. In this contest, the bamboo shoots dietary fibers prepared by different methods had different adsorption characteristics for polyphenols. The aim of current study was to compare the saturated adsorption capacity of three kinds of dietary fibers to polyphenols, and screen suitable processing technology. We believed that our findings could be to provide basis for the development of new functional foods.

A randomized phase II, open-label and multicenter study of combination regimens of bortezomib at two doses by subcutaneous injection for newly diagnosed multiple myeloma patients.

PURPOSE: Combinations of bortezomib (Velcade), cyclophosphamide and dexamethasone have shown significant efficacy and safety for patients of newly diagnosed multiple myeloma (NDMM). In this study, we compared the efficacy and safety of modified VCD regimens with novel changes in bortezomib dose and schedule for NDMM. METHODS: Eighty-five NDMM patients from multiple centers were randomly assigned to a high-dose (1.6 mg/m2) (group A) or a low-dose (1.3 mg/m2) (group B) bortezomib, administrated on days 1, 6, 11, and 16 subcutaneously in a 4-week cycle for nine cycles, combined with 40 mg dexamethasone on bortezomib days and cyclophosphamide 300 mg/m2 on days 1-3 intravenously. RESULTS: After four cycles, complete response (CR) or better in group A (43.6%) was higher than that in group B (12.8%) (P = 0.002). During induction, for patients with R-ISS stage III, the CR or better rate in group A was superior to that in group B (P = 0.01). Of patients < 65, the CR or better rate of group A was superior to that of group B (P = 0.004). Rapid onset of CR occurred in group A (P < 0.01). Meanwhile, rate of 3-4 diarrhea was higher in group A (P = 0.03), which caused higher rate of dose reduction for patients ≥ 65 (P = 0.041). No significant difference between the two groups in PFS and OS. CONCLUSIONS: The studied high-dose VCD as induction regimen had an improved CR rate, especially in patients < 65 or with R-ISS stage III, and is feasible for young and high-risk patients. Trial registration ClinicalTrials.gov: NCT02086942.

Mechanistic toxicity of DEHP at environmentally relevant concentrations (ERCs) and ecological risk assessment in the Three Gorges Reservoir Area, China.

Di-(2-ethylhexyl) phthalate (DEHP) associated in vitro/vivo toxicity at current environmentally relevant concentration (ERC) with attendant ecological risks in the Three Gorges Reservoir Area (TGRA) is still elusive. Responding to this challenge, a novel integrated study based on analytical and biological assays was designed to elucidate the underlying mechanisms for toxicity of DEHP and its ecological risks at ERC. In this study, GC-MS analysis showed that the highest environmental concentration of DEHP in the TGRA surface water was nearly double that of WHO and USEPA standards. Both distribution and ecological risk decreased from the upper to middle and lower reaches of the TGRA. In vitro toxicity was assessed by cell viability and DNA damage assays: DEHP exposure at ERCs (100-800 µg/L) caused significant reduction in cell viability and elevated DNA damage. Further, DEHP exposure above 400 µg/L resulted in enhanced migration behavior of cancer cells. For in vivo toxicity assessment, short term acute exposure (7 d, 400 µg/L) apparently activated the PI3K-AKT-mTOR pathway, and chronic low-level exposure (3 months, 10-33 µg/L) suppressed the hypothalamus pituitary thyroid (HPT) axis pathway in zebrafish. In addition, acute low-level exposure (5 d, 33-400 µg/L) to DEHP increased aryl hydrocarbon receptor (AhR) activity in Tg(cyp1a:gfp) zebrafish in a concentration-dependent manner. In short, DEHP at ERC has extended potential to induce diverse in vitro and in vivo toxicity at concentrations that also cause impairment of biochemical function in aquatic species of the TGRA.

New toxicogenetic insights and ranking of the selected pharmaceuticals belong to the three different classes: A toxicity estimation to confirmation approach.

Tetracycline hydrochloride (TH), indomethacin (IM), and bezafibrate (BF) belong to the three different important classes of pharmaceuticals, which are well known for their toxicity and environmental concerns. However, studies are still elusive to highlight the mechanistic toxicity of these pharmaceuticals and rank them using both, the toxicity prediction and confirmation approaches. Therefore, we employed the next generation toxicity testing in 21st century (TOX21) tools and estimated the in vitro/vivo toxic endpoints of mentioned pharmaceuticals, and then confirmed them using in vitro/vivo assays. We found significant resemblance in the results obtained via both approaches, especially in terms of in vivo LC50 s and developmental toxicity that ranked IM as most toxic among the studied pharmaceuticals. However, TH appeared most toxic with the lowest estimated AC50s, the highest experimental IC50s, and DNA damages in vitro. Contrarily, IM was found as congener with priority concern to activate the Pi3k-Akt-mTOR pathway in vitro at concentrations substantially lower than that of TH and BF. Further, IM exposure at lower doses (2.79-13.97 µM) depressed the pharmaceuticals detoxification phase I (CYP450 s), phase II (UGTs, SULTs), and phase III (TPs) pathways in zebrafish, whereas, at relatively higher doses, TH (2.08-33.27 µM) and BF (55.28-884.41 µM) partially activated these pathways, which ultimately caused the developmental toxicity in the following order: IM > TH > BF. In addition, we also ranked these pharmaceuticals in terms of their particular toxicity to myogenesis, hematopoiesis, and hepatogenesis in zebrafish embryos. Our results revealed that IM significantly affected myogenesis, hematopoiesis, and hepatogenesis, while TH and BF induced prominent effects on hematopoiesis via significant downregulation of associated genetic markers, such as drl, mpx, and gata2a. Overall, our findings confirmed that IM has higher toxicity than that of TH and BF, therefore, the consumption of these pharmaceuticals should be regulated in the same manner to ensure human and environmental safety.

MB4-2/MB4-3 transcripts of IGH-MMSET fusion gene in t(4;14)pos multiple myeloma indicate poor prognosis.

Multiple myeloma (MM) patients with t(4;14) is a heterogeneous group. Prognostic tools capable of predicting the outcome of patients are currently lacking. The MM SET domain (MMSET) protein is universally overexpressed and has been suggested to have an important tumorigenic role. This study analyzed whether the overexpression of full-length (MB4-1) or truncated forms (MB4-2 and MB4-3) of MMSET influence the prognosis of t(4;14)pos MM patients. A total of 53 symptomatic t(4;14)pos MM patients were retrospectively analyzed. RT-PCR was performed using cDNA from purified CD138+ bone marrow plasma cells to analyze expression and clinical significance of the IGH-MMSET fusion transcripts corresponding to MB4-1, MB4-2 and MB4-3 breakpoints. Among the patients, 25 (47.2%), 12 (22.6%) and 16 (30.2%) had the MB4-1, MB4-2 and MB4-3 breakpoints, respectively. When adjusted to the established prognostic variables including del(17p), ISS stage, serum LDH and serum calcium levels, the pooled MB4-2/MB4-3 subgroup remained a powerful independent adverse factor for PFS (P=0.013) and OS (P=0.029). Bortezomib-based therapy significantly improved the survival of the MB4-1 subgroup but could not overcome the negative effect of the MB4-2/MB4-3 breakpoints. Our results indicate that MB4-2/MB4-3 breakpoints with truncated forms of MMSET define a subset of t(4;14)posMM with poor prognosis.

Potential health risk of heavy metals in the leather manufacturing industries in Sialkot, Pakistan.

This is a systematical report on the potential health risk of heavy metals from the leather industries in Pakistan based on multiple biological matrices of the exposed workers and indoor dust samples. The adverse impacts of heavy metals on the oxidative enzyme and their risks to workers' health were also explored. Our results indicated that the level of Cr in indoor industrial dust was more than twice, compared to the background household dust. Blood, urine and hair samples of exposed workers showed significantly high concentrations of heavy metals, compared to those in the control group. Superoxide dismutase (SOD) level in the blood samples expressed significant positive correlation with Cr and Ni. Total hazard quotients (HQs)/hazard index (HI) were >1, and Cr (VI) exhibited higher cancer risks than that of Cd in the exposed workers. In addition, the PCA-MLR analysis confirmed that the industrial sections; cutting, shivering/crusting, and stitching were the principal contributors of heavy metals in the biological entities of the workers. Taken together, our results highlighted the occupationally exposed groups would likely to experience the potential health risks due to excessive exposure to the heavy metals from the leather industries.

Perturbation effect of reduced graphene oxide quantum dots (rGOQDs) on aryl hydrocarbon receptor (AhR) pathway in zebrafish.

Graphene quantum dots (GQDs) has been widely used in enormous fields, however, the inherent molecular mechanism of GQDs for potential risks in biological system is still elusive to date. In this study, the outstanding reduced graphene quantum dots (rGOQDs) with the QY as high as 24.62% were successfully synthesized by the improved Hummers method and DMF hydrothermal treatment approach. The rGOQDs were N-doped photoluminescent nanomaterials with functional groups on the surface. The fluorescent bio-imaging was performed by exposing zebrafish in different concentrations of the as-prepared rGOQDs, and the distribution of rGOQDs was successfully observed. Moreover, the developmental toxicity and genotoxicity were evaluated to further investigate the potential hazard of rGOQDs. The result indicated that rGOQDs were responsible for the dose-dependent abnormalities on the development of zebrafish. Since the real-time polymerase chain reaction (RT-PCR) results showed that the expression of cyp1a was the highest expression in the selected genes and significantly up-regulated 8.49 fold in zebrafish, the perturbation of rGOQDs on aryl hydrocarbon receptor (AhR) pathway was investigated by using the Tg(cyp1a:gfp) zebrafish for the first time. The results demonstrated that rGOQDs significantly increased the green fluorescent protein (GFP) expression promoted by cyp1a in a dose-dependent manner, which was also further confirmed by the western blotting. This study offered an opportunity to reveal the potential hazards of in vivo bio-probes, which provided a valuable reference for investigating the graphene-based materials on the disturbance of AhR pathway in biological organisms.

[Acute Promyelocytic Leukemia Developed during Imatinib Therapy for Gastrointestinal Stromal Tumors].

OBJECTIVE: To investigate the clinicopathologic and molecular characteristics of acute promyelocytic leukemia(APL) developed during imatinib therapy for gastrointestinal stromal tumors(GIST). METHODS: A 49-year-old woman was hospitalized for abdominal pain. The abdominal CT revealed a gastric mass. Laparoscopic resection of the tumor was performed. The histopathologic analysis showed poorly differentiated malignant cell infiltration with epithelioid features. Immunohistochemistry staining of these cells was positive for CD117 and CD34. GIST was confirmed and imatinib treatment was given. RESULTS: After 1 year,the patient developed progressive pancytopenia. Bone marrow aspirate showed marked hyperplasia of bone marrow cells with 92.5% promyelocyte, consistent with APL. Cytogenetic analysis demonstrated t(15;17)(q22;q21) as the sole abnormality. PML/RARα fusion gene was positive and Kit mutation was negative. After combined treatment with ATRA, arsenic trioxide and idarubicin, patient achieved cytogenetic and molecular remission. CONCLUSION: The metachronous coexistence of GIST with APL is uncommon. The potential nonrandom association and causal relationship between these malignancies remained to be investigated. Further studies would be necessary to clarify the relationship between imatinib and secondary malignancies in GIST patients.

[Clinical and Immunophenotypic Properties of Small Cell Variant of T-cell Prolymphocytic Leukemia].

OBJECTIVE: To investigate the clinical, morphologic and immunophenotypic properties of the patients with small cell variant of T-cell prolymphocytic leukaemia(T-PLL). METHODS: Peripheral blood and bone marrow cytomorphologic and immunophenotypic examination, and T-cell receptor(TCR) gene rearrangement detection were used to verify the diagnosis for 2 patients with lymphocytosis. Two patients were treated with combined chemotherapeutic protocol based on fludarabine. RESULTS: At diagnosis of case 1, the main lymphocytes of peripheral blood smear were the small mature lymphocytes without nucleoli. The immunophenotype of the cells was CD3+CD5+CD7+CD4+CD8+TCRα/ß+. The patient achieved complete remission after treatment with combined with CTX of fludarabine. The disease relapsed at 32 months after diagnosis. The abnormal lymphocytes were medium-sized ones with a visible nucleolus. Immunophenotyping showed that the leukemic cells were predominantly CD8 positive(CD3+CD5+CD7+CD4-CD8+TCRα/ß+). Both the peripheral blood and bone marrow cells of case 2 were predominanthy the mature lymphocytes, and their immunophenotype was HLA-DR+CD7+CD5+CD4+CD3+CD2+CD56+cCD3+TCRα/ß+. The combined fludarabine therapy was ineffective. CONCLUSION: Immunophenotypical switch from CD4+CD8+ to CD4-CD8+ may be associated with a poor response to chemotherapy. CD56 expression is an independent poor prognostic factor for primary refractory disease in T-PLL and may be considered for implementing risked-adapted therapeutic strategies.

Diverse toxicological risks of PAHs in surface water with an impounding level of 175m in the Three Gorges Reservoir Area, China.

The impounding level of 175m for the Three Gorges Reservoir (TGR) is of vital importance for efficient flood control, power generation and convenient navigation in China. However, little is known about the spatial distribution and toxicological risks of major pollutants in the Three Gorges Reservoir Area (TGRA) at that stage. The aim of this study is to probe the ubiquitous polycyclic aromatic hydrocarbons (PAHs) contamination and toxicological impacts in the surface water of the TGRA at the highest water impoundment level of 175m. Our results showed that the Æ©PAHs levels ranged from 83 to 1631ng/L in the upper reaches, 354 to 1159ng/L in the middle reaches, and 23 to 747ng/L in the lower reaches of the TGRA. Source apportionment of PAHs indicated that coal combustion, industrial emissions, heavy traffic, agriculture and shipping activities were the primary sources. Compositional pattern highlighted >85% dominancy of low molecular weight (LMW) PAHs in the reservoir. Risk assessment based on risk quotients (RQs) implied moderate to high ecological risks: the upper reaches>the middle reaches>the lower reaches. However, gene expression profiles portrayed contrary scenario because of the presence of relatively higher footprints of high molecular weight (HMW) PAHs in the middle and the lower reaches, which was confirmed by Cox hazard proportional model. Moreover, the transgenic zebrafish Tg(cyp1a:gfp) induced by PAHs also expressed stronger fluorescent signals in the middle and lower reaches. Taken together, different approaches were employed to firstly reveal the real status of ecological toxicity of PAHs and explore the underlying mechanisms at the highest impounding level of 175m in the TGRA.

[Clinicopathologic Characteristics and Outcome of Isolated Ovarian Relapse in Adolescent with Acute Lymphoblastic Leukemia].

OBJECTIVE: To investigate the clinicopathologic characteristics,diagnosis and treatment of isolated ovarian relapse of acute lymphoblastic leukemia(ALL). METHODS: A 16-year-old girl presented with complaints of bone and joint pain. The peripheral blood and bone marrow(BM) smears showed 32% and 72% blasts, respectively, which were myeloperoxidase-negative. The blasts were positive for HLA-DR, TdT, CD10, CD19, CD22 and cCD79a and negative for CD34, CD5, CD7, CD13, CD33, CD56 and MPO detected by flow cytometry. BM cytogenetic analysis and fusion gene screening revealed t(1;19)(q23;p13) and E2A/PBX1. She was diagnosed as B-cell acute lymphoblastic leukemia (B-ALL) and was treated with CALGB8811 protocol. She presented lower abdominal pain with intermittent colick at 7 months after complete remission. The pelvic ultrasound showed a lobulated mixed echogenic mass in the right ovary, and an exploratory laparotomy was performed. RESULTS: Pathologic examination and immunohistochemistry of resected ovarian tumor revealed extensive infiltration by lymphoblasts with positive for TdT, CD20, CD43 and CD79a. Further investigations failed to reveal any other extramedullary involvement. Hemogram, peripheral blood and bone marrow smear examination were unremarkable at the same time. The isolated extramedullary ovarian relapse of ALL was confirmed. Simultaneous, the detection of minimal residual disease by multiparametric flow cytometry showed positive with 5.0×10-4. The reinduction chemotherapy including a high-dose methotrexate and cytarabine was given to the patients. She experienced the second ovarian relapse after 1 year and refused further treatment. CONCLUSION: Although uncommon, ovarian recurrence after chemotherapy for ALL should be considered in the patients with suggestive symptoms. Screening by pelvic ultrasonography may be valuble for early detection of pelvic disease in ALL.

Altitudinal variation in age and body size in Yunnan pond frog (Pelophylax pleuraden).

Large-scale systematic patterns of body size are a basic concern of evolutionary biology. Identifying body size variation along altitudinal gradients may help us to understand the evolution of life history of animals. In this study, we investigated altitudinal variation in body size, age and growth rate in Chinese endemic frog, Pelophylax pleuraden. Data sampled from five populations covering an altitudinal span of 1413 to 1935 m in Sichuan province revealed that body size from five populations did not co-vary with altitudes, not following Bergmann's rule. Average adult SVL differed significantly among populations in males, but not in females. For both sexes, average adult age differed significantly among populations. Post-metamorphic growth rate did not co-vary with altitude, and females grew faster than males in all populations. When controlling the effect of age, body size did not differ among populations in both sexes, suggesting that age did not affect variation in body size among populations. For females, there may be other factors, such as the allocation of energy between growth and reproduction, that eliminated the effect of age on body size. To our minds, the major reason of body size variation among populations in male frogs may be related to individual longevity. Our findings also suggest that factors other than age and growth rate may contribute to size differences among populations.

Identification of a novel partner gene, TPR, fused to FGFR1 in 8p11 myeloproliferative syndrome.

The 8p11 myeloproliferative syndrome (EMS) is an aggressive neoplasm caused by the fusion of various partner genes to fibroblast growth factor receptor 1 (FGFR1). Various FGFR1 fusions are associated with subtly distinct disease phenotypes. Here, we report a new translocation at the FGFR1 locus in a patient who carried t(1;8)(q25;p11.2) and presented with myeloproliferative neoplasm-like symptoms. The patient was characterized by myeloid hyperplasia of bone marrow, markedly elevated numbers of monocytes, and normal to mildly elevated eosinophils. Initial fluorescent in situ hybridization analysis confirmed that FGFR1 in this patient was disrupted. Subsequent analysis led to the identification of a novel translocation, in which exon 23 of the translocated promoter region (TPR) gene at chromosome band 1q25 was fused to exon 13 of FGFR1 (RefSeq NM_0231102.2). The TPR portion of the fusion protein contains putative functional motifs including an N-terminal TprMet domain, nuclear pore complexes associating domain, and multiple coiled-coil domains. It is likely that one or more of the motifs from TPR contribute to dimerization, resulting in constitutive activation of the FGFR1 kinase domain. Our results further support a critical role of FGFR1 in the pathogenesis of EMS and may lead to more accurate diagnosis and potential targeted therapy.

[Clinic-pathologic characteristics of autoimmune diseases combined with non-Hodgkin's lymphoma].

This study was aimed to investigate the clinical characteristics and treatment of patients with autoimmune disease combined with non-Hodgkin lymphoma (NHL). The clinical characteristics and pathologic patterns of 6 patients with NHL who concurrently suffered from autoimmune diseases were analysed retrospectively from aspects of clinical course, pathologic features, and therapy. Treatment outcomes for autoimmune diseases and NHL were observed. The results showed that 6 patients included 4 females and 2 males, range in age from 28 to 65 years with a median age of 56 years. The autoimmune diseases are Sjogren's syndrome (SS, 2 cases), rheumatoid arthritis (RA, 2 cases), ulcerative colitis (UC, 1 case) and Crohn's disease (CD, 1 case). The NHL diseases located not only in the lymph node (n = 3) but also in extranodal sites (n = 3). Histologically, 3 cases were diffuse large B cell lymphoma (DLBCL), 2 cases were extranodal nasal NK/T lymphoma (ENKL) and 1 case was peripheral T cell lymphoma, not otherwise specified. Based on CD10, Bcl-6 and MUM1 expression patterns, all 3 DLBCL were classified as non-GC subtype. EBER positive tumor cells were detected in 2 case of ENKL. 5 patients achieved a complete remission (83%) and 1 patient was primary drug-resistant after CHOP chemotherapy or involved radiotherapy. Median survival from the time of lymphoma diagnosis was 3 years. 1 patient showed clinical improvement of the SS symptoms, 2 patients (CD and UC) showed stable state of disease and 2 patients with RA and 1 patient with SS needed continuing treatment for their autoimmune diseases after chemotherapy for NHL. It is concluded that the development of NHL is one of the most serious complications in patients with autoimmune diseases. There is an increased frequency of non-GC subtype DLBCL. CHOP combined with or without radiotherapy proves to be effective for autoimmune disease patients with aggressive NHL but ineffective for concurrent autoimmune diseases.