Compositionally graded III-nitride alloys: building blocks for efficient ultraviolet optoelectronics and power electronics.

Wide bandgap aluminum gallium nitride (AlGaN) semiconductor alloys have established themselves as the key materials for building ultraviolet (UV) optoelectronic and power electronic devices. However, further improvements to device performance are lagging, largely due to the difficulties in precisely controlling carrier behavior, both carrier generation and carrier transport, within AlGaN-based devices. Fortunately, it has been discovered that instead of using AlGaN layers with fixed Al compositions, by grading the Al composition along the growth direction, it is possible to (1) generate high-density electrons and holes via polarization-induced doping; (2) manipulate carrier transport behavior via energy band modulation, also known as 'band engineering'. Consequently, such compositionally graded AlGaN alloys have attracted extensive interest as promising building blocks for efficient AlGaN-based UV light emitters and power electronic devices. In this review, we focus on the unique physical properties of graded AlGaN alloys and highlight the key roles that such graded structures play in device exploration. Firstly, we elaborate on the underlying mechanisms of efficient carrier generation and transport manipulation enabled by graded AlGaN alloys. Thereafter, we comprehensively summarize and discuss the recent progress in UV light emitters and power electronic devices incorporating graded AlGaN structures. Finally, we outline the prospects associated with the implementation of graded AlGaN alloys in the pursuit of high-performance optoelectronic and power electronic devices.

The Cry48Aa N-terminal Domain is Responsible for Cry48Aa-Cry49Aa Interaction in Lysinibacillus sphaericus Toxin.

The Cry48Aa/Cry49Aa binary toxin from Lysinibacillus sphaericus is composed of a three-domain Cry-like toxin (Cry48Aa) and a binary-like protein (Cry49Aa) that work together to kill Culex quinquefasciatus mosquito larvae through a novel interaction between its two components. The aim of this study was to identify the functional regions of Cry48Aa that were involved in the interaction with Cry49Aa. Eight Cry48Aa truncated fragments were constructed from both N- and C-termini and expressed in Escherichia coli. Only the individual or combined N69K truncated fragment, a Cry48Aa N-terminal derivative consisting of three domains, showed larvicidal activity against C. quinquefasciatus larvae, while the other fragments exhibited significant loss of biological activity. Far-Western dot blot analysis showed that Cry48Aa N-terminal regions had the ability to bind to Cry49Aa protein. These results demonstrate that the N-terminal domain of Cry48Aa plays a crucial role in responsible for the full virulence to mosquito larvae and the interaction with Cry49Aa as a binary toxin.

Pure curcumin increases the expression of SOCS1 and SOCS3 in myeloproliferative neoplasms through suppressing class I histone deacetylases.

Suppressors of cytokine signaling, SOCS1 and SOCS3, are important negative regulators of Janus kinase 2/signal transducers and activators of transcription signaling, which is constitutively activated in myeloproliferative neoplasms (MPNs) and leukemia. Curcumin has been shown to possess anticancer activity through different mechanisms. However, whether curcumin can regulate the expression of SOCS1 and SOCS3 is still unknown. Here, we found that curcumin elevated the expression of SOCS1 and SOCS3 via triggering acetylation of histone in the regions of SOCS1 and SOCS3 promoter in K562 and HEL cells. As a novel histone deacetylases (HDACs) inhibitor, curcumin inhibited HDAC enzyme activities and decreased the levels of HDAC1, 3 and 8 but not HDAC2. Knockdown of HDAC8 by small interfering RNA markedly elevated the expression of SOCS1 and SOCS3. Moreover, ectopic expression of HDAC8 decreased the levels of SOCS1 and SOCS3. Thus, HDAC8 plays an important role in the modulation of SOCS1 and SOCS3 by curcumin. Also, trichostatin A (TSA), an inhibitor of HDACs, increased the levels of SOCS1 and SOCS3. Furthermore, curcumin increased the transcript levels of SOCS1 and SOCS3 and significantly inhibited the clonogenic activity of hematopoietic progenitors from patients with MPNs. Finally, curcumin markedly inhibited HDAC activities and decreased HDAC8 levels in primary MPN cells. Taken together, our data uncover a regulatory mechanism of SOCS1 and SOCS3 through inhibition of HDAC activity (especially HDAC8) by curcumin. Thus, being a relative non-toxic agent, curcumin may offer a therapeutic advantage in the clinical treatment for MPNs.

Catalytic activation of carbohydrates as formaldehyde equivalents for Stetter reaction with enones.

We disclose the first catalytic activation of carbohydrates as formaldehyde equivalents to generate acyl anions as one-carbon nucleophilic units for a Stetter reaction. The activation involves N-heterocyclic carbene (NHC)-catalyzed C-C bond cleavage of carbohydrates via a retro-benzoin-type process to generate the acyl anion intermediates. This Stetter reaction constitutes the first success in generating formal formaldehyde-derived acyl anions as one-carbon nucleophiles for non-self-benzoin processes. The renewable nature of carbohydrates, accessible from biomass, further highlights the practical potential of this fundamentally interesting catalytic activation.

Shifts in composition and function of bacterial communities reveal the effect of small barriers on nitrous oxide and methane accumulation in fragmented rivers.

Rivers are often blocked by barriers to form different habitats, but it is not clear whether this change will affect the accumulation of N2O and CH4 in rivers. Here, low barriers (less than 2 m, LB) increased N2O concentration by 1.13 times and CH4 decreased by 0.118 times, while high barriers (higher than 2 m, less than 5 m high, HB) increased N2O concentration by 1.19 times and CH4 by 2.76 times. Co-occurrence network analysis indicated LB and HB can promote the enrichment of Cyanobium and Chloroflexi, further limiting complete denitrification and increasing N2O accumulation. The LB promotes methanotrophs (Methylocystis, Methylophilus, and Methylotenera) to compete with denitrifiers (Pseudomonas) in water, and reduce CH4 accumulation. While the HB can promote the methanotrophs to compete with nitrifiers (Nitrosospira) in sediment, thus reducing the consumption of CH4. LB and HB reduce river velocity, increase water depth, and reduce dissolved oxygen (DO), leading to enrichment of nirS-type denitrifiers and the increase of N2O concentration in water. Moreover, the HB reduces DO concentration and pmoA gene abundance in water, which can increase the accumulation of CH4. In light of the changes in the microbial community and variation in N2O and CH4 accumulation, the impact of fragmented rivers on global greenhouse gas emissions merits further study.

[Clinical study of correlation between the expression of ICBP90 and hematopoietic suppression in patients with chronic benzene poisoning].

OBJECTIVE: To observe the change of ICBP90 expression in patients with chronic benzene poisoning and explore the correlation between the expression of ICBP90 and benzene-induced hematotoxicity. METHODS: The bone marrow samples were from 13 chronic benzene poisoning cases with hematopoietic suppression, 11 chronic benzene poisoning cases with hematopoietic regeneration and 10 controls. Western-blot was applied to detect the ICBP90 expression in bone marrow mononuclear cells (BMNCs). The correlation between ICBP90 expression and hematopoietic suppression in patients with chronic benzene poisoning was analyzed. RESULTS: The ICBP90 expression of BMNCs in 13 chronic benzene poisoning cases with hematopoietic suppression was significantly lower than that in controls (P < 0.01). The ICBP90 expression of BMNCs in 11 chronic benzene poisoning cases with hematopoietic regeneration was significantly higher than those in controls and 13 chronic benzene poisoning cases with hematopoietic suppression (P < 0.05 or P < 0.01), respectively. There were good correlations between the expression of ICBP90 and white blood cell and platelet counts in patients with chronic benzene poisoning (r(1) = 0.555,P = 0.006; r(2) = 0.854,P < 0.01). CONCLUSION: The ICBP90 expression of BMNCs in the chronic benzene poisoning cases with hematopoietic suppression decreased significantly, and the ICBP90 expression of BMNCs in the chronic benzene poisoning cases with hematopoietic regeneration increased significantly. There was good correlation between hematopoietic suppression and ICBP90 expression in patients with chronic benzene poisoning.

Culex quinquefasciatus alpha-glucosidase serves as a putative receptor of the Cry48Aa toxin from Lysinibacillus sphaericus.

The Cry48Aa/Cry49Aa toxin of Lysinibacillus sphaericus shows specific toxicity towards larvae of Culex spp. Individual Cry48Aa and Cry49Aa subunits interact with distinct target sites in the larval midgut and overcome the resistance of Culex to the Bin toxin. However, the toxin-binding proteins have not yet been identified. The present study aimed to identify Cry48Aa-binding proteins in Culex quinquefasciatus. Pulldown assays using C. quinquefasciatus midgut brush-border membrane fractions (BBMFs) identified a class of proteins, including aminopeptidases (APNs), protease m1 zinc metalloproteases, alkaline phosphatases (ALPs), and maltases, that could be potentially involved in the mode of action of this toxin. RNA interference analysis showed that silenced larvae treated with dsRNA of the alpha-glucosidase (named Glu71) gene were more tolerant of the Cry48Aa/Cry49Aa toxin, which induced less than 20% mortality. The amino acid sequence of Glu71 exhibited 42% identity with Cqm1/Cpm1, which acted as a Bin toxin receptor. Toxin binding assays showed that Cry48Aa had a high specific binding capacity for the Glu71 protein, whereas Cry49Aa exhibited no specific binding. Overall, our results showed that Glu71 is a Cry48-binding protein involved in Cry48Aa/Cry49Aa toxicity.

Encapsulins from Ca. Brocadia fulgida: An effective tool to enhance the tolerance of engineered bacteria (pET-28a-cEnc) to Zn2.

Zn2+ is largely discharged from many industries and poses a severe threat to the environment, making its remediation crucial. Encapsulins, proteinaceous nano-compartments, may protect cells against environmental stresses by sequestering toxic substances. To determine whether hemerythrin-containing encapsulins (cEnc) from anammox bacteria Ca. Brocadia fulgida can help cells deal with toxic substances such as Zn2+, we transferred cEnc into E.coli by molecular biology technologies for massive expression and then cultured them in media with increasing Zn2+ levels. The engineered bacteria (with cEnc) grew better and entered the apoptosis phase later, while wild bacteria showed poor survival. Furthermore, tandem mass tag-based quantitative proteomic analysis was used to reveal the underlying regulatory mechanism by which the genetically-engineered bacteria (with cEnc) adapted to Zn2+ stress. When Zn2+ was sequestered in cEnc as a transition, the engineered bacteria presented a complex network of regulatory systems against Zn2+-induced cytotoxicity, including functions related to ribosomes, sulfur metabolism, flagellar assembly, DNA repair, protein synthesis, and Zn2+ efflux. Our findings offer an effective and promising stress control strategy to enhance the Zn2+ tolerance of bacteria for Zn2+ remediation and provide a new application for encapsulins.

Proteomics reveals the enhancing mechanism for eliminating toxic hydroxylamine from water by nanocompartments containing hydroxylamine oxidase.

Hydroxylamine (NH2OH) is a potentially toxic pollutant when it is present in water, as it can damage both bacteria and the human body. It is still difficult to eliminate the toxic NH2OH in water. Here, we showed that the model bacterium (Escherichia coli) with nanocompartments encapsulated with hydroxylamine oxidase (HAO) can remove NH2OH from water. In addition, the removal efficiency of NH2OH by genetically modified bacteria (with HAO-nanocompartments) was 3.87 mg N L-1 h-1, and that of wild-type bacteria (without HAO-nanocompartments) was only 1.86 mg N L-1 h-1. Label-free quantitative proteomics indicated that the nanocompartments containing HAO enhanced bacterial activity by inducing the up-regulation of proteins involved in stress and stimulus responses, and decreased their intracellular NH2OH concentration. Moreover, the synthesis of proteins involved in energy metabolism, gene expression, and other processes in bacterial was enhanced under hydroxylamine stress, and these changes increased the resistance of bacterial to NH2OH. This work can aid our understanding of the toxic effects of NH2OH on bacteria as well as the development of new approaches to eliminate NH2OH in water.

[Toxicity Management and Efficacy Evaluation of BCMA-CART in the Treatment of Relapsed and Refractory Multiple Myeloma].

OBJECTIVE: To investigate the toxicity management and efficacy evaluation of BCMA-chimeric antigen receptor T cells(CART) in the treatment of relapsed and refractory multiple myeloma (MM). METHODS: The efficacy and adverse reactions of 21 patients with MM who received BCMA-CART treatment at the First Affiliated Hospital of Wenzhou Medical University from December 2017 to September 2020 were evaluated, and the efficacy assessment and survival analysis for high-risk patients and non-high-risk patients were evaluated. RESULTS: After infusion of BCMA-CART cells in 21 MM patients, the number of effective cases was 17, of which the complete remission (sCR/CR) was 10, and the partial remission (VGPR/PR) was 7. The median OS time for all patients was 19.4 months, and the median PFS time was 7.9 months. The number of patients with extramedullary disease(EMD), high-risk genetics, and ISS stage Ⅲ were 5, 15 and 8, and the effective number was 3, 11 and 6, respectively. The treatment of 3 patients without high-risk factors was effective. The median OS and median PFS of patients with EMD were 14.2 and 2.5 months, respectively, which were shorter than those of patients without EMD (19.4 months and 8.9 months, respectively). The median OS and median PFS of patients with high-risk cytogenetic factors and ISS Ⅲ were not significantly different from those of non-high-risk patients. Cytokine release syndrane (CRS) occurred in 20 patients, of which 14 cases were Grade 1 CRS, while 6 were Grade 2, no CRS of Grade 3 or above occurred. IL-6 receptor inhibitors were used in 9 patients. All CRS were controlled effectively, and no patients had neurological toxicity. CONCLUSION: BCMA-CART is a certain curative effect in the treatment of relapsed and refractory multiple myeloma, and the adverse reactions can be well controlled through close monitoring and timely treatment.

Bacterially self-assembled encapsulin nanocompartment for removing silver from water.

Compartmentalization can protect cells from the interference of external toxic substances by sequestering toxic products. We hypothesized that proteinaceous nanocompartments may be a feasible candidate material to be added to genetically modified bacteria for the sequestration of toxic environmental products, which would open up a new bioremediation pathway. Here, we showed that the model bacterium (Escherichia coli) with self-assembling nanocompartments can remove silver (Ag) from water. Transmission electron microscopy and energy dispersive X-ray (TEM-EDX) analysis showed that the nanocompartments combined stably with silver in vitro. In addition, when exposed to 30 µM AgNO3, the survival rate of genetically modified bacteria (with nanocompartments) was 86%, while it was just 59% in the wild-type bacteria (without nanocompartments). Label-free quantitative proteomics indicated that the nanocompartments enhanced bacterial activity by inducing the up-regulation of protein processing and secondary metabolites, and decreased their intracellular silver concentration, both of which contributed to their increased resistance to toxic silver. This study on nanocompartments has contributed to a deeper understanding of how bacteria respond to environmental stressors like heavy metal pollutants in water. The technology promises to provide a new strategy for recycling heavy metals from sewage.

Interaction between CD9 and PI3K­p85 activates the PI3K/AKT signaling pathway in B­lineage acute lymphoblastic leukemia.

Our previous study has shown that CD9 knockdown could suppress cell proliferation, adhesion, migration and invasion, and promote apoptosis and the cytotoxicity of chemotherapeutic drugs in the B­lineage acute lymphoblastic leukemia (B­ALL) cell line SUP­B15. In this study, we further investigated the molecular mechanism underlying the effects of CD9 on leukemic cell progression and the efficacy of chemotherapeutic agents in B­ALL cells. Using the CD9­knockdown SUP­B15 cells, we demonstrated that the silencing of the CD9 gene significantly reduced the expression of phosphorylated­phosphatidylinositol­3 kinase (p­PI3K), phosphorylated­protein kinase B (p­AKT), P­glycoprotein (P­gp), multidrug resistance­associated protein 1 (MRP1), breast cancer resistance protein (BCRP), matrix metalloproteinase 2 (MMP2) and phosphorylated­focal adhesion kinase (p­FAK). In addition, glutathione S­transferase (GST) pull­down assay showed the binding between CD9 and both PI3K­p85α and PI3K­p85ß in vitro, while co­immunoprecipitation assay showed the binding between CD9 and both PI3K­p85α and PI3K­p85ß in vivo. Furthermore, the PI3K/AKT inhibitor LY294002 mirrored the effects of CD9 knockdown in SUP­B15 cells. Taken together, these findings demonstrated that CD9 activates the PI3K/AKT signaling pathway through direct interaction with PI3K­p85 in B­ALL cells. Our data provide evidence for the inhibition of the PI3K/AKT pathway as a novel therapeutic option in CD9 antigen­positive B­ALL.

Synergistic apoptosis induction in leukemic cells by miR-15a/16-1 and arsenic trioxide.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate target gene expression through translation repression or messenger RNA degradation. MiR-15a and 16-1 form a cluster at the chromosomal region 13q14, which is frequently deleted or down-regulated in chronic lymphocytic leukemia. Arsenic trioxide (As(2)O(3), ATO) has been successfully applied to treat acute promyelocytic leukemia (APL). Its combination with other drugs presented therapeutic activities in hematologic and solid tumors. Here we investigated the potential synergy between miR-15a/16-1 and ATO on Bcr-Abl positive leukemic K562 cells. In this study, we found that combination of miR-15a/16-1 and ATO synergistically induced growth inhibition and apoptosis in K562 cells. The apoptosis, at least in part, through regulating mitochondrial function including the release of cytochrome c and loss of mitochondrial transmembrane potential, also activation of caspase-3 and degradation of poly-adenosine diphosphate-ribose polymerase. However, the expression of Bcr-Abl was not affected by ATO and/or miR-15a/16-1. Moreover, apoptotic synergy between miR-15a/16-1 and ATO was observed in Bcr-Abl negative leukemic cell lines and primary leukemic cells. Taken together, these findings suggested that the combined regiment of miR-15a/16-1 and ATO might be a potential therapeutic remedy for the treatment of leukemia.

A self-assembled nanocompartment in anammox bacteria for resisting intracelluar hydroxylamine stress.

Anammox bacteria play an important role in the global nitrogen cycle, but research on anammoxosome structure is still in its initial stages. In particular, the anammox bacteria genome contains nanocompartments gene loci. However, the function and structure of the nanocompartments in anammox bacteria is poorly understood. We apply genetic engineering to demonstrate the self-assembled nanocompartments of anammox bacteria. The encapsulin shell protein (cEnc) and cargo protein hydroxylamine oxidoreductase (HAO) can self-assemble to form regular nanocompartments (about 128 nm in diameter) in vitro. Cell growth curve tests show that nanocompartments help model bacteria resist hydroxylamine (NH2OH) stress. Batch test results and transcriptional data show that cEnc and HAO are highly expressed in response to the negative effects of NH2OH on anammox efficiency, predicting a potential role of nanocompartments in helping anammox bacteria resist NH2OH stress. These findings improve our understanding of the mechanisms by which anammox bacteria respond to harmful environmental metabolites.

[Effect of Hydroxylamine on Community of ANAMMOX Sludge].

At present, the anaerobic ammonium oxidation (ANAMMOX) process has the advantages of high efficiency, low energy consumption, and low sludge quantity, and it therefore has broad application prospects in sewage nitrogen removal. Hydroxylamine is not only an intermediate product of ANAMMOX metabolism but also an inhibitor. However, the effect of hydroxylamine on the activity of ANAMMOX is not clear. Therefore, we investigated the ANAMMOX activity under the condition of adding different concentrations of hydroxylamine (40-80 mg·L-1) through a hydroxylamine batch experiment. It was found that hydroxylamine can inhibit ANAMMOX activity. However, it was impossible to determine the threshold of ANAMMOX bacteria to hydroxylamine. Next, the mRNA levels of hydrazine oxidase (HZO) in different reactors were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR), and it was found that the expression levels of HZO peak and then decrease with an increase of hydroxylamine concentration. It was suggested that the tolerated hydroxylamine concentration was within 60-70 mg·L-1 for 3.12 g·L-1 ANAMMOX granular sludge. Moreover, a 16S rRNA high-throughput sequencing method was used to analyze the structure and function of ANAMMOX granules in microbial communities in the reactor. It was found that the addition of an appropriate concentration of hydroxylamine (50 mg·L-1) helped to enhance the cellular motility of bacteria and promoted the composition of ANAMMOX bacteria, providing a better ecological balance.

Normal Absolute Monocyte Count at the Time of Relapse is Associated with Improved Survival After First Salvage Therapy in Adult Patients with Early Relapsed B-Lineage Acute Lymphoblastic Leukemia.

BACKGROUND: Peripheral monocytes, a key cell type for innate immunity, have been shown to be associated with survival in various types of hematological malignancies. However, no previous studies regarding the prognostic impact of peripheral absolute monocyte count (AMC) in early relapsed B-lineage acute lymphoblastic leukemia (B-ALL) have been reported. METHODS: Forty-nine cases of early relapsed adult B-ALL were reviewed. The upper (0.80 × 109/L) and lower limits (0.12 × 109/L) of the normal value for AMC were used as cut-off points. Kaplan-Meier curves and Log rank test were used for comparison of overall survival (OS). The univariate and multivariate Cox proportional hazards models were used for investigating the factors associated with OS. RESULTS: More than half (59.2%) of all patients showed a normal AMC (0.12-0.80 × 109/L). The median follow-up was 5.3 months from the start of first salvage therapy. Univariate analysis revealed that normal AMC (versus low/high AMC) at the time of relapse was a prognostic factor for improved OS (P = 0.021). On multivariate analysis, normal AMC (versus low/high AMC) at the time of relapse remained an independent prognostic factor for improved OS (hazard ratio = 0.43, P = 0.030). CONCLUSION: AMC at the time of relapse, which can be easily derived from routine clinical laboratory testing of complete blood count, might be used as a prognostic marker for survival outcomes in adult patients with early relapsed B-ALL.

Burkitt lymphoma-associated network construction and important network motif analysis.

Biological and medical researchers have discovered numerous transcription factors (TFs), microRNAs (miRNAs) and genes associated with Burkitt lymphoma (BL) through individual experiments; however, their regulatory mechanisms remain unclear. In the present study, BL-dysregulated and BL-associated networks were constructed to investigate these mechanisms. All data and regulatory associations were from known data resources and literature. The dysregulated network consisted of dysregulated TFs, miRNAs and genes, and partially determined the pathogenesis mechanisms underlying BL. The BL-associated network consisted of BL-associated TFs, miRNAs and genes. It has been indicated that the network motif consisted of TFs, miRNAs and genes serve potential functions in numerous biological processes within cancer. Two of the most studied network motifs are feedback loop (FBL) and feed-forward loop (FFL). The important network motifs were extracted, including the FBL motif, 3-nodes FFL motif and 4-nodes motif, from BL-dysregulated and BL-associated networks, and 10 types of motifs were identified from BL-associated network. Finally, 26/31 FBL motifs, 45/75 3-nodes FFL motifs and 54/94 4-nodes motifs were obtained from the dysregulated/associated networks. A total of four TFs (E2F1, NFKB1, E2F4 and TCF3) exhibit complicated regulation associations in BL-associated networks. The biological network does not demonstrate the dysregulated status for healthy people. When the individual becomes unwell, their biological network exhibits a dysregulated status. If the dysregulated status is regulated to a normal status by a number of medical methods, the diseases may be treated successfully. BL-dysregulated networks serve important roles in pathogenesis mechanisms underlying BL regulation of the dysregulated network, which may be an effective strategy that contributes to gene therapy for BL.