Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of aggressive T-cell lymphomas with no treatment consensus and poor prognosis. We herein described an extraordinary refractory ca...Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of aggressive T-cell lymphomas with no treatment consensus and poor prognosis. We herein described an extraordinary refractory case of PTCL-NOS with widely involvement of subcutaneous tissue, which showed an excellent response to Semustine personal- ized chemotherapy based on the detection finding of positive O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation. This is the first english report to indicate that single nitrosourea agent such as Semustine may have good efficacy and safety for widespread subcutaneous involvement of PTCL-NOS with positive MGMT promoter methylation.展开更多
Objectives: To conduct health risk assessment of drinking water pesticide residues and its annual trend analysis in Shenzhen City. Methods: The samples of product water, pipe water and secondary supply water from 2011...Objectives: To conduct health risk assessment of drinking water pesticide residues and its annual trend analysis in Shenzhen City. Methods: The samples of product water, pipe water and secondary supply water from 2011 to 2013 were collected and analyzed. The evaluation models of health risk assessments for children and adults on the 12 non-carcinogenic materials (namely heptachlor, pentachlorophenol, hexachlorocyclohexane, hexachlorobenzene, DDT, malathion, glyphosate, dimethoate, bentazone, atrazine, chlorothalonil, furadan) were recommended by the U.S. Environmental Protection Agency (US EPA). Results: The results showed that the maximums of the measured indicators in the above were controlled in accordance with the National Health Standards (GB5749-2006) published by Ministry of Health in China. The adults and children’s health indices (HIs) of the 12 non-carcinogenic materials were greater than 1 (2.323 - 6.312). Dimethoate residue in factory and peripheral water was the largest risks of harm among the non-carcinogenic pollutants measured. And its HIi (Its Hli) was also greater than 1 (1.995 - 5.094) and followed by hexachlorobenzene and heptachlor. Annual rising trend on health risk of the 12 pesticide residues indicated that their HIT on adults was 2323. 18 × 10-3 in 2011, 2340. 18 × 10-3 in 2012 and 2431. 97 × 10-3 in 2013, and HIT on children was 2965. 07 × 10-3 in 2011, 2986. 77 × 10-3 in 2012 and 3103. 93 × 10-3 in 2013, respectively. This study also suggested that the average risk of peripheral water samples (HIT was equal to 2619. 64 × 10-3) was greater than the factory samples’ (HIT was the same as 2366. 92 × 10-3), and the children’s health risk was greater than the adults’. Conclusions: Health risks of drinking water pesticide residues in Shenzhen have exceeded the threshold values. The dimethoate was the main hazard and had been rising annually, and the children’s health risk was greater than the adults’.展开更多
The combination of immunotherapy and chemotherapy is regarded as a promising approach for the treatment of certain types of cancer. However, the underlying mechanisms need to be fully investigated to guide the design ...The combination of immunotherapy and chemotherapy is regarded as a promising approach for the treatment of certain types of cancer. However, the underlying mechanisms need to be fully investigated to guide the design of more efficient protocols for cancer chemoimmunotherapy. It is well known that danger-associated molecular patterns （DAMPs） can activate immune cells, including dendritic cells （DCs）, via Toll-like receptors （TLRs）; however, the role of DAMPs released from chemical drug-treated tumor cells in the activation of the immune response needs to be further elucidated. Here, we found that colorectal cancer （CRC） cells treated with oxaliplatin （OXA） and/or 5-fluorouracil （5-Fu） released high levels of high-mobility group box 1 （HMGB1） and heat shock protein 70 （HSP70）. After OXA/5-Fu therapy, the sera of CRC patients also exhibited increased levels of HMGB1 and HSP70, both of which are well-known DAMPs. The supernatants of dying CRC cells treated with OXA/5-Fu promoted mouse and human DC maturation, with upregulation of HLA-DR, CD80 and CD86 expression and enhancement of IL-lp, TNF-a, MIP-la, MIP-lp, RANTES and IP-IO production. Vaccines composed of DCs pulsed with the supernatants of chemically stressed CRC cells induced a more significant IFN-y-producing Thl response both in vitroand in vivo. However, the supernatants of chemically stressed CRC cells failed to induce phenotypic maturation and cytokine production in TLR4-deficient DCs, indicating an essential role of TLR4 in DAMP-induced DC maturation and activation. Furthermore, pulsing with the supernatants of chemically stressed CRC cells did not efficiently induce an IFN-y-producing Thl response in TLR4-deficient DCs. Collectively, these results demonstrate that DAMPs released from chemically stressed cancer cells can activate DCs viaTLR4 and enhance the induction of an anti-tumor T-cell immune response, delineating a clinically relevant immuno-adjuvant pathway triggered by DAMPs.展开更多
Chloroplast biogenesis requires the coordinated expression of chloroplast and nuclear genes.Here, we show that EMB1270, a plastid-localized pentatricopeptide repeat(PPR) protein, is required for chloroplast biogenesis...Chloroplast biogenesis requires the coordinated expression of chloroplast and nuclear genes.Here, we show that EMB1270, a plastid-localized pentatricopeptide repeat(PPR) protein, is required for chloroplast biogenesis in Arabidopsis thaliana.Knockout of EMB1270 led to embryo arrest,whereas a mild knockdown mutant of EMB1270 displayed a virescent phenotype. Almost no photosynthetic proteins accumulated in the albino emb1270 knockout mutant. By contrast, in the emb1270 knockdown mutant, the levels of ClpP1 and photosystem I(PSI) subunits were significantly reduced, whereas the levels of photosystem II(PSII) subunits were normal. Furthermore, the splicing efficiencies of the clpP1.2,ycf3.1, ndhA, and ndhB plastid introns were dramatically reduced in both emb1270 mutants. RNA immunoprecipitation revealed that EMB1270 associated with these introns in vivo. In an RNA electrophoretic mobility shift assay(REMSA), a truncated EMB1270 protein containing the 11 Nterminal PPR motifs bound to the predicted sequences of the clpP1.2, ycf3.1, and ndhA introns.In addition, EMB1270 specifically interacted with CRM Family Member 2(CFM2). Given that CFM2 is known to be required for splicing the same plastid RNAs, our results suggest that EMB1270 associates with CFM2 to facilitate the splicing of specific group II introns in Arabidopsis.展开更多
文摘Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of aggressive T-cell lymphomas with no treatment consensus and poor prognosis. We herein described an extraordinary refractory case of PTCL-NOS with widely involvement of subcutaneous tissue, which showed an excellent response to Semustine personal- ized chemotherapy based on the detection finding of positive O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation. This is the first english report to indicate that single nitrosourea agent such as Semustine may have good efficacy and safety for widespread subcutaneous involvement of PTCL-NOS with positive MGMT promoter methylation.
文摘Objectives: To conduct health risk assessment of drinking water pesticide residues and its annual trend analysis in Shenzhen City. Methods: The samples of product water, pipe water and secondary supply water from 2011 to 2013 were collected and analyzed. The evaluation models of health risk assessments for children and adults on the 12 non-carcinogenic materials (namely heptachlor, pentachlorophenol, hexachlorocyclohexane, hexachlorobenzene, DDT, malathion, glyphosate, dimethoate, bentazone, atrazine, chlorothalonil, furadan) were recommended by the U.S. Environmental Protection Agency (US EPA). Results: The results showed that the maximums of the measured indicators in the above were controlled in accordance with the National Health Standards (GB5749-2006) published by Ministry of Health in China. The adults and children’s health indices (HIs) of the 12 non-carcinogenic materials were greater than 1 (2.323 - 6.312). Dimethoate residue in factory and peripheral water was the largest risks of harm among the non-carcinogenic pollutants measured. And its HIi (Its Hli) was also greater than 1 (1.995 - 5.094) and followed by hexachlorobenzene and heptachlor. Annual rising trend on health risk of the 12 pesticide residues indicated that their HIT on adults was 2323. 18 × 10-3 in 2011, 2340. 18 × 10-3 in 2012 and 2431. 97 × 10-3 in 2013, and HIT on children was 2965. 07 × 10-3 in 2011, 2986. 77 × 10-3 in 2012 and 3103. 93 × 10-3 in 2013, respectively. This study also suggested that the average risk of peripheral water samples (HIT was equal to 2619. 64 × 10-3) was greater than the factory samples’ (HIT was the same as 2366. 92 × 10-3), and the children’s health risk was greater than the adults’. Conclusions: Health risks of drinking water pesticide residues in Shenzhen have exceeded the threshold values. The dimethoate was the main hazard and had been rising annually, and the children’s health risk was greater than the adults’.
文摘The combination of immunotherapy and chemotherapy is regarded as a promising approach for the treatment of certain types of cancer. However, the underlying mechanisms need to be fully investigated to guide the design of more efficient protocols for cancer chemoimmunotherapy. It is well known that danger-associated molecular patterns （DAMPs） can activate immune cells, including dendritic cells （DCs）, via Toll-like receptors （TLRs）; however, the role of DAMPs released from chemical drug-treated tumor cells in the activation of the immune response needs to be further elucidated. Here, we found that colorectal cancer （CRC） cells treated with oxaliplatin （OXA） and/or 5-fluorouracil （5-Fu） released high levels of high-mobility group box 1 （HMGB1） and heat shock protein 70 （HSP70）. After OXA/5-Fu therapy, the sera of CRC patients also exhibited increased levels of HMGB1 and HSP70, both of which are well-known DAMPs. The supernatants of dying CRC cells treated with OXA/5-Fu promoted mouse and human DC maturation, with upregulation of HLA-DR, CD80 and CD86 expression and enhancement of IL-lp, TNF-a, MIP-la, MIP-lp, RANTES and IP-IO production. Vaccines composed of DCs pulsed with the supernatants of chemically stressed CRC cells induced a more significant IFN-y-producing Thl response both in vitroand in vivo. However, the supernatants of chemically stressed CRC cells failed to induce phenotypic maturation and cytokine production in TLR4-deficient DCs, indicating an essential role of TLR4 in DAMP-induced DC maturation and activation. Furthermore, pulsing with the supernatants of chemically stressed CRC cells did not efficiently induce an IFN-y-producing Thl response in TLR4-deficient DCs. Collectively, these results demonstrate that DAMPs released from chemically stressed cancer cells can activate DCs viaTLR4 and enhance the induction of an anti-tumor T-cell immune response, delineating a clinically relevant immuno-adjuvant pathway triggered by DAMPs.
基金This study was supported by the National Natural Science Foundation of China(31100180,31470337,31570231)Shanghai Natural Science Foundation(18ZR1428200)+1 种基金The Fund of Innovation Program of Shanghai Municipal Education Commission(2021-01-07-00-02-E00117)Shanghai Engineering Research Center of Plant Germplasm Resources(17DZ2252700)。
文摘Chloroplast biogenesis requires the coordinated expression of chloroplast and nuclear genes.Here, we show that EMB1270, a plastid-localized pentatricopeptide repeat(PPR) protein, is required for chloroplast biogenesis in Arabidopsis thaliana.Knockout of EMB1270 led to embryo arrest,whereas a mild knockdown mutant of EMB1270 displayed a virescent phenotype. Almost no photosynthetic proteins accumulated in the albino emb1270 knockout mutant. By contrast, in the emb1270 knockdown mutant, the levels of ClpP1 and photosystem I(PSI) subunits were significantly reduced, whereas the levels of photosystem II(PSII) subunits were normal. Furthermore, the splicing efficiencies of the clpP1.2,ycf3.1, ndhA, and ndhB plastid introns were dramatically reduced in both emb1270 mutants. RNA immunoprecipitation revealed that EMB1270 associated with these introns in vivo. In an RNA electrophoretic mobility shift assay(REMSA), a truncated EMB1270 protein containing the 11 Nterminal PPR motifs bound to the predicted sequences of the clpP1.2, ycf3.1, and ndhA introns.In addition, EMB1270 specifically interacted with CRM Family Member 2(CFM2). Given that CFM2 is known to be required for splicing the same plastid RNAs, our results suggest that EMB1270 associates with CFM2 to facilitate the splicing of specific group II introns in Arabidopsis.
