Due to the heterogeneity of tumors,single phototherapy cannot completely ablate tumors and inhibit tumor metastasis.To overcome these,we formulated targeted and multifunctional polymersomes ABC@ICGIMQ-LHRH(AIRL)that e...Due to the heterogeneity of tumors,single phototherapy cannot completely ablate tumors and inhibit tumor metastasis.To overcome these,we formulated targeted and multifunctional polymersomes ABC@ICGIMQ-LHRH(AIRL)that encapsulated Toll-like receptor(TLR)7/8 agonist imiquimod(IMQ)and photosensitizer indocyanine green(ICG)in the hydrophobic layer as well as bubble-generator NH_(4)HCO_(3) in the hydrophilic cavity to inhibit the growth of primary and distant tumors,and prevent tumor metastasis through synergistic photoimmunotherapy.The AIRL polymersomes exhibited uniform and stable size,and high drug encapsulation efficiency,acid/reduction/laser responsiveness,excellent photothermal conversion efficiency,effective reactive oxygen species generation,high tumor accumulation.AIRL could be effectively internalized by dendritic cells(DCs),achieve lysosome escape and enhance DCs maturation.The synergistic photoimmunotherapy via AIRL polymersomes remarkably promoted the differentiation and activation of T cells,elevated strong systemic immune response to eradicate primary tumors and inhibit the growth of distant tumors.Simultaneously,the endurable immunological memory prevented tumor metastasis,which provided a promising nanoplatform for the combination therapy of cancer.展开更多
Immunostimulatory therapies based on pattern recognition receptors(PRRs)have emerged as an effective approach in the fight against cancer,with the ability to recruit tumor-specific lymphocytes in a low-immunogenicity ...Immunostimulatory therapies based on pattern recognition receptors(PRRs)have emerged as an effective approach in the fight against cancer,with the ability to recruit tumor-specific lymphocytes in a low-immunogenicity tumor environment.The agonist cyclic dinucleotides(CDNs)of the stimulator of interferon gene(STING)are a group of very promising anticancer molecules that increase tumor immunogenicity by activating innate immunity.However,the tumor immune efficacy of CDNs is limited by several factors,including relatively narrow cytokine production,inefficient delivery to STING,and rapid clearance.In addition,a single adjuvant molecule is unable to elicit a broad cytokine response and thus cannot further amplify the anticancer effect.To address this problem,two or more agonist molecules are often used together to synergistically enhance immune efficacy.In this work,we found that a combination of the STING agonist CDGSF and the Toll-like receptor 7/8(TLR7/8)agonist 522 produced a broader cytokine response.Subsequently,we developed multicomponent nanovaccines(MCNVs)consisting of a PC7A polymer as a nanocarrier encapsulating the antigen OVA and adjuvant molecules.These MCNVs activate bone marrow-derived dendritic cells(BMDCs)to produce multiple proinflammatory factors that promote antigen cross-presentation to stimulate specific antitumor Tcell responses.In in vivo experiments,we observed that MCNVs triggered a strong T-cell response in tumor-infiltrating lymphocytes,resulting in significant tumor regression and,notably,a 100%survival rate in mice through 25 days without other partnering therapies.These data suggest that our nanovaccines have great potential to advance cancer immunotherapy with increased durability and potency.展开更多
<strong>Introduction:</strong> Surgical management takes place, after a certain period of evolution, on particularly severe forms of secondary hyperparathyroidism, resistant to medical treatment. Subtotal ...<strong>Introduction:</strong> Surgical management takes place, after a certain period of evolution, on particularly severe forms of secondary hyperparathyroidism, resistant to medical treatment. Subtotal parathyroidectomy is an effective technique in the treatment of these disorders. <strong>Method:</strong> Our study is retrospective of 33 cases of hyperparathyroidism secondary to chronic renal failure in dialysis patients operated by the 7/8 technique. Identified over a period of 10 years (January 2010 to December 2019), in the ENT department of the Fann University Hospital. <strong>Results:</strong> Out of 33 cases of secondary hyperparathyroidism, the average age of our patients was 51.24 years with a sex ratio of 0.43. Causal nephropathy was dominated by nephro-angiosclerosis, which was found in 27.27% of cases. Bone pain found in 23 patients or 69.69% was the predominant clinical sign. The average calcemia was 92.7 mg/l. Parathormone was dosed in all our patients and the average was 1611.05 ng/l. The consequences were clinically marked by recurrent paresis in one patient. No case of hematoma or postoperative infection was found. On the biological level 10 patients or 30.30% had a transient hypocalcaemia. The results were marked by a drop in PTH in 23 patients or 78.78% of cases. <strong>Conclusion:</strong> Subtotal parathyroidectomy remains an effective and beneficial therapeutic method for kidney failure patients with secondary hyperparathyroidism.展开更多
A 900 MHz fractional-N synthesizer is designed for the UHF transceiver. The VCO with a 4 bits capacitor bank covers 823–1061 MHz that implements 16（2^4）sub-bands. A 7/8 dual-modulus prescaler is implemented with a ...A 900 MHz fractional-N synthesizer is designed for the UHF transceiver. The VCO with a 4 bits capacitor bank covers 823–1061 MHz that implements 16（2^4）sub-bands. A 7/8 dual-modulus prescaler is implemented with a phase-switching circuit and high-speed flip–flops, which are composed of source coupled logic. The proposed synthesizer phase-locked loop is demonstrated with a 50 k Hz band width by a low 12.95 MHz reference clock, and offers a better phase noise and band width tradeoff. To reduce the out-band phase noise, a 4-levels 3-order single-loop sigma–delta modulator is applied. When its relative frequency resolution is settled to 10^-6, the testing results show that the phase noises are –120.6 dBc/Hz at 1 MHz and –95.0 dBc/Hz at 100 k Hz. The chip is2.1 mm^2 in UMC 0.18μm CMOS. The power is 36 m W at a 1.8 V supply.展开更多
1.care about,care for,take care of (1)这三个动词短语均可表示"喜欢…‘关心"之意,后接n.或v.-ing形式作宾语。He cared nothing about/for skating.他对滑冰没有兴趣。In our class,we care for/about each other.
1.Complete the map of each site based on what you hear on the tape. 1)based on what you hear on the tape是过去分词短语,在句子中作定语,修饰site。be based on意为"以……为根据"。This novel is based on historica...1.Complete the map of each site based on what you hear on the tape. 1)based on what you hear on the tape是过去分词短语,在句子中作定语,修饰site。be based on意为"以……为根据"。This novel is based on historical facts.展开更多
基金financially supported by National Natural Science Foundation of China(Nos.82172090,82302390 and 82072059)CAMS Innovation Fund for Medical Sciences(Nos.2021-I2M-1-058 and 2022-I2M-1-023)+3 种基金China Postdoctoral Science Foundation(No.2022M720502)Tianjin Municipal Natural Science Foundation(No.22JCQNJC00070)CAMS Union Young Scholars Support Program(No.2022051)Fundamental Research Funds for the Central Universities(No.2019PT320028)。
文摘Due to the heterogeneity of tumors,single phototherapy cannot completely ablate tumors and inhibit tumor metastasis.To overcome these,we formulated targeted and multifunctional polymersomes ABC@ICGIMQ-LHRH(AIRL)that encapsulated Toll-like receptor(TLR)7/8 agonist imiquimod(IMQ)and photosensitizer indocyanine green(ICG)in the hydrophobic layer as well as bubble-generator NH_(4)HCO_(3) in the hydrophilic cavity to inhibit the growth of primary and distant tumors,and prevent tumor metastasis through synergistic photoimmunotherapy.The AIRL polymersomes exhibited uniform and stable size,and high drug encapsulation efficiency,acid/reduction/laser responsiveness,excellent photothermal conversion efficiency,effective reactive oxygen species generation,high tumor accumulation.AIRL could be effectively internalized by dendritic cells(DCs),achieve lysosome escape and enhance DCs maturation.The synergistic photoimmunotherapy via AIRL polymersomes remarkably promoted the differentiation and activation of T cells,elevated strong systemic immune response to eradicate primary tumors and inhibit the growth of distant tumors.Simultaneously,the endurable immunological memory prevented tumor metastasis,which provided a promising nanoplatform for the combination therapy of cancer.
基金supported by the National Key R&D Program of China(Nos.2019YFA0904200 and 2018YFA0507600)Tsinghua University Spring Breeze Fund(No.2020Z99CFY042)the National Natural Science Foundation of China(No.92053108).
文摘Immunostimulatory therapies based on pattern recognition receptors(PRRs)have emerged as an effective approach in the fight against cancer,with the ability to recruit tumor-specific lymphocytes in a low-immunogenicity tumor environment.The agonist cyclic dinucleotides(CDNs)of the stimulator of interferon gene(STING)are a group of very promising anticancer molecules that increase tumor immunogenicity by activating innate immunity.However,the tumor immune efficacy of CDNs is limited by several factors,including relatively narrow cytokine production,inefficient delivery to STING,and rapid clearance.In addition,a single adjuvant molecule is unable to elicit a broad cytokine response and thus cannot further amplify the anticancer effect.To address this problem,two or more agonist molecules are often used together to synergistically enhance immune efficacy.In this work,we found that a combination of the STING agonist CDGSF and the Toll-like receptor 7/8(TLR7/8)agonist 522 produced a broader cytokine response.Subsequently,we developed multicomponent nanovaccines(MCNVs)consisting of a PC7A polymer as a nanocarrier encapsulating the antigen OVA and adjuvant molecules.These MCNVs activate bone marrow-derived dendritic cells(BMDCs)to produce multiple proinflammatory factors that promote antigen cross-presentation to stimulate specific antitumor Tcell responses.In in vivo experiments,we observed that MCNVs triggered a strong T-cell response in tumor-infiltrating lymphocytes,resulting in significant tumor regression and,notably,a 100%survival rate in mice through 25 days without other partnering therapies.These data suggest that our nanovaccines have great potential to advance cancer immunotherapy with increased durability and potency.
文摘<strong>Introduction:</strong> Surgical management takes place, after a certain period of evolution, on particularly severe forms of secondary hyperparathyroidism, resistant to medical treatment. Subtotal parathyroidectomy is an effective technique in the treatment of these disorders. <strong>Method:</strong> Our study is retrospective of 33 cases of hyperparathyroidism secondary to chronic renal failure in dialysis patients operated by the 7/8 technique. Identified over a period of 10 years (January 2010 to December 2019), in the ENT department of the Fann University Hospital. <strong>Results:</strong> Out of 33 cases of secondary hyperparathyroidism, the average age of our patients was 51.24 years with a sex ratio of 0.43. Causal nephropathy was dominated by nephro-angiosclerosis, which was found in 27.27% of cases. Bone pain found in 23 patients or 69.69% was the predominant clinical sign. The average calcemia was 92.7 mg/l. Parathormone was dosed in all our patients and the average was 1611.05 ng/l. The consequences were clinically marked by recurrent paresis in one patient. No case of hematoma or postoperative infection was found. On the biological level 10 patients or 30.30% had a transient hypocalcaemia. The results were marked by a drop in PTH in 23 patients or 78.78% of cases. <strong>Conclusion:</strong> Subtotal parathyroidectomy remains an effective and beneficial therapeutic method for kidney failure patients with secondary hyperparathyroidism.
文摘A 900 MHz fractional-N synthesizer is designed for the UHF transceiver. The VCO with a 4 bits capacitor bank covers 823–1061 MHz that implements 16（2^4）sub-bands. A 7/8 dual-modulus prescaler is implemented with a phase-switching circuit and high-speed flip–flops, which are composed of source coupled logic. The proposed synthesizer phase-locked loop is demonstrated with a 50 k Hz band width by a low 12.95 MHz reference clock, and offers a better phase noise and band width tradeoff. To reduce the out-band phase noise, a 4-levels 3-order single-loop sigma–delta modulator is applied. When its relative frequency resolution is settled to 10^-6, the testing results show that the phase noises are –120.6 dBc/Hz at 1 MHz and –95.0 dBc/Hz at 100 k Hz. The chip is2.1 mm^2 in UMC 0.18μm CMOS. The power is 36 m W at a 1.8 V supply.
文摘1.care about,care for,take care of (1)这三个动词短语均可表示"喜欢…‘关心"之意,后接n.或v.-ing形式作宾语。He cared nothing about/for skating.他对滑冰没有兴趣。In our class,we care for/about each other.
文摘1.Complete the map of each site based on what you hear on the tape. 1)based on what you hear on the tape是过去分词短语,在句子中作定语,修饰site。be based on意为"以……为根据"。This novel is based on historical facts.
