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1.
Plant Cell ; 36(4): 919-940, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38180963

RESUMO

Soil salinity results in oxidative stress and heavy losses to crop production. The S-acylated protein SALT TOLERANCE RECEPTOR-LIKE CYTOPLASMIC KINASE 1 (STRK1) phosphorylates and activates CATALASE C (CatC) to improve rice (Oryza sativa L.) salt tolerance, but the molecular mechanism underlying its S-acylation involved in salt signal transduction awaits elucidation. Here, we show that the DHHC-type zinc finger protein DHHC09 S-acylates STRK1 at Cys5, Cys10, and Cys14 and promotes salt and oxidative stress tolerance by enhancing rice H2O2-scavenging capacity. This modification determines STRK1 targeting to the plasma membrane or lipid nanodomains and is required for its function. DHHC09 promotes salt signaling from STRK1 to CatC via transphosphorylation, and its deficiency impairs salt signal transduction. Our findings demonstrate that DHHC09 S-acylates and anchors STRK1 to the plasma membrane to promote salt signaling from STRK1 to CatC, thereby regulating H2O2 homeostasis and improving salt stress tolerance in rice. Moreover, overexpression of DHHC09 in rice mitigates grain yield loss under salt stress. Together, these results shed light on the mechanism underlying the role of S-acylation in RLK/RLCK-mediated salt signal transduction and provide a strategy for breeding highly salt-tolerant rice.


Assuntos
Oryza , Tolerância ao Sal , Tolerância ao Sal/genética , Oryza/metabolismo , Peróxido de Hidrogênio/metabolismo , Homeostase , Dedos de Zinco , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
2.
Plant Cell ; 35(9): 3604-3625, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37325884

RESUMO

Catalase (CAT) is often phosphorylated and activated by protein kinases to maintain hydrogen peroxide (H2O2) homeostasis and protect cells against stresses, but whether and how CAT is switched off by protein phosphatases remains inconclusive. Here, we identified a manganese (Mn2+)-dependent protein phosphatase, which we named PHOSPHATASE OF CATALASE 1 (PC1), from rice (Oryza sativa L.) that negatively regulates salt and oxidative stress tolerance. PC1 specifically dephosphorylates CatC at Ser-9 to inhibit its tetramerization and thus activity in the peroxisome. PC1 overexpressing lines exhibited hypersensitivity to salt and oxidative stresses with a lower phospho-serine level of CATs. Phosphatase activity and seminal root growth assays indicated that PC1 promotes growth and plays a vital role during the transition from salt stress to normal growth conditions. Our findings demonstrate that PC1 acts as a molecular switch to dephosphorylate and deactivate CatC and negatively regulate H2O2 homeostasis and salt tolerance in rice. Moreover, knockout of PC1 not only improved H2O2-scavenging capacity and salt tolerance but also limited rice grain yield loss under salt stress conditions. Together, these results shed light on the mechanisms that switch off CAT and provide a strategy for breeding highly salt-tolerant rice.


Assuntos
Oryza , Catalase/genética , Catalase/metabolismo , Oryza/metabolismo , Peróxido de Hidrogênio/metabolismo , Proteína Fosfatase 1/metabolismo , Tolerância ao Sal/genética , Homeostase , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
3.
Circulation ; 150(2): 91-101, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38742915

RESUMO

BACKGROUND: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention. METHODS: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore. Patients were randomized to receive either cangrelor or placebo initiated before the primary percutaneous coronary intervention procedure on top of oral ticagrelor. The key exclusion criteria included presenting <6 hours of symptom onset; previous MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance. The primary efficacy end point was acute MI size by cardiovascular magnetic resonance within the first week expressed as percentage of the left ventricle mass (%LVmass). Microvascular obstruction was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety end point was Bleeding Academic Research Consortium-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test (reported as median [first quartile-third quartile]), and categorical variables were compared by Fisher exact test. A 2-sided P<0.05 was considered statistically significant. RESULTS: Of 209 recruited patients, 164 patients (78%) completed the acute cardiovascular magnetic resonance scan. There were no significant differences in acute MI size (placebo, 14.9% [7.3-22.6] %LVmass versus cangrelor, 16.3 [9.9-24.4] %LVmass; P=0.40) or the incidence (placebo, 48% versus cangrelor, 47%; P=0.99) and extent of microvascular obstruction (placebo, 1.63 [0.60-4.65] %LVmass versus cangrelor, 1.18 [0.53-3.37] %LVmass; P=0.46) between placebo and cangrelor despite a 2-fold decrease in platelet reactivity with cangrelor. There were no Bleeding Academic Research Consortium-defined major bleeding events in either group in the first 48 hours. CONCLUSIONS: Cangrelor administered at the time of primary percutaneous coronary intervention did not reduce acute MI size or prevent microvascular obstruction in patients with ST-segment-elevation MI given oral ticagrelor despite a significant reduction of platelet reactivity during the percutaneous coronary intervention procedure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03102723.


Assuntos
Monofosfato de Adenosina , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Masculino , Feminino , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Pessoa de Meia-Idade , Método Duplo-Cego , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Monofosfato de Adenosina/administração & dosagem , Idoso , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/administração & dosagem , Resultado do Tratamento , Singapura , Ticagrelor/uso terapêutico , Ticagrelor/administração & dosagem
4.
Opt Express ; 32(5): 6800-6813, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38439377

RESUMO

Digital mask projection lithography (DMPL) technology is gaining significant attention due to its characteristics of free-mask, flexibility, and low cost. However, when dealing with target layouts featuring sizes smaller than the wavelength scale, accurately producing resist patterns that closely match the target layout using conventional methods to design the modulation coefficients of digital masks produced by spatial light modulators (SLM) becomes challenging. Here, we present digital inversion lithography technology (DILT), which offers what we believe to be a novel approach to reverse engineer the modulation coefficients of digital masks. In the case of binary amplitude modulation, DILT achieves a remarkable reduction in pattern errors (PE), reaching the original 0.26. At the same time, in the case of the gray amplitude modulation, the PE can be reduced to the original 0.05, which greatly improves the high-fidelity transfer of the target layout. This significant improvement enhances the accuracy of target design transfer. By leveraging the capabilities of DILT, DMPL can now attain higher precision and reliability, paving the way for more advanced applications in the field of micro-nano device manufacturing.

5.
Opt Lett ; 49(4): 810-813, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38359188

RESUMO

When the critical dimension (CD) of resist patterns nears the resolution limit of the digital micromirror device (DMD) maskless projection lithography (DMD-MPL), significant distortion can emerge in the silicon wafer due to the optical proximity effect (OPE). The significant distortion (breakpoints, line-end scaling, corner rounding, etc.) between resist patterns and target patterns results in reduced lithographic quality. To address this issue, we have proposed a pixel-based optical proximity correction (PB-OPC) method used for the hot-spot patterns with subwavelength sizes specifically designed for DMD-MPL. Employing an end-to-end learning neural network, the PB-OPC algorithm is both straightforward and efficient. A well-trained U-net framework facilitates the mapping from unoptimized masks to optimized masks. Experimental exposure trials have demonstrated that this method not only corrects OPC in general patterns but also effectively rectifies hot-spot patterns. The pattern error (PE) value can be reduced by about 30% in the design layouts. We believe this approach holds the potential to enhance the resolution and fidelity of resist patterns in DMD maskless lithography.

6.
Opt Lett ; 48(11): 3087-3090, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37262287

RESUMO

The Dammann grating (DG), which redistributes a collimated laser beam into a spot array with a uniform intensity, is a widely adopted approach for profile measurement. Conventional DGs for dense spot projection are binary phase gratings with precisely designed groove structures, which suffer from low efficiency, poor uniformity, and a hard-to-fabricate fine feature size when utilized for a large field of view (FOV). Here, we propose a new, to the best of our knowledge, hybrid DG architecture consisting of two different grating periods which effectively generates an engineering M2 × N2 spot array with a non-complex structural design. As a proof-of-concept, a dual-period hybrid DG with a two-scale grating period ratio of 11.88 µm/95.04 µm (∼1/8) is designed and fabricated as a means to generate a dense 72 × 72 diffraction spot array with a FOV of 17° × 17°. In addition, the DG exhibits superior performance, with a high efficiency (>60%) and a low non-uniformity (<18%) at a wavelength of 532 nm. This kind of hybrid DG constructed from photoresist patterns with a minimum feature size of ∼1.2 µm can be perfectly fabricated by maskless projection lithography for large-scale and low-cost production. The proposed dual-period hybrid DG can pave the way for depth-perception-related applications such as face unlocking and motion sensing.

7.
J Oral Pathol Med ; 52(7): 583-592, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36829264

RESUMO

BACKGROUND: Oral tongue squamous cell carcinoma tends to metastasize to cervical lymphatic nodes early which leads to a 50% drop of survival rate. CXCL1 could be secreted by LNMTca8113 cell induced lymphatic endothelial cells and promoted LNMTca8113 cell migration. The current study aimed to further explore the effect of CXCL1 on the proliferation and migration abilities of tongue cancer cells and the prognostic value of serum CXCL1 in oral tongue squamous cell carcinoma. METHODS: Cell proliferation and migration ability were analysed by CCK8 assays and transwell migration assays. Immunofluorescence technique was used to show cytoskeleton. GST pull-down assay was applied to quantify the activation of GTPases. Blood samples of patients were collected and clinicopathological characteristics were analysed. RESULTS: CXCL1 could promote cancer cell proliferation in appropriate concentration by PI3K/AKT pathway. It also regulated the activation of Rho GTPases to mediate the rearrangements of cytoskeleton to promote tumour cell migration. Level of plasma CXCL1 could predict the possibility of early lymphatic metastasis and had a predictive value in progression-free survival and overall survival. CONCLUSIONS: CXCL1 could promote oral cancer cell proliferation, migration and invasion in vitro and contributed theoretical knowledge for the target selection in molecular targeted therapy. Level of plasma CXCL1 might serve as a biomarker for prognosis in oral tongue squamous cell carcinoma patients.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias da Língua , Humanos , Neoplasias da Língua/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Fosfatidilinositol 3-Quinases , Linhagem Celular Tumoral , Prognóstico , Movimento Celular , Proliferação de Células , Quimiocina CXCL1
8.
J Craniofac Surg ; 34(5): 1464-1467, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37410573

RESUMO

The reconstruction of buccal-penetrating defects remains challenging. The present study aims to explore the application value of the lateral arm free flap (LAFF) on the reconstruction of buccal-penetrating defects with the hope of providing a better option for clinical practice. Nineteen patients with this kind of issue posed by either tumor resections or deformities in the craniofacial regions were recruited in this study, and LAFF was employed to reconstruct these defects by double folding and individually designing the flap. All the flaps prepared for these subjects in our study survived, and the postoperative assessment of these subjects receiving LAFF revealed that this approach to managing buccal-penetrating defects is able to achieve satisfactory results in terms of appearance and functional recovery. Therefore, our study suggests that LAFF is 1 of the promising flaps to reconstruct the buccal-penetrating defects.


Assuntos
Retalhos de Tecido Biológico , Neoplasias Bucais , Procedimentos de Cirurgia Plástica , Humanos , Retalhos de Tecido Biológico/cirurgia , Neoplasias Bucais/cirurgia , Recuperação de Função Fisiológica
9.
Zhongguo Zhong Yao Za Zhi ; 48(2): 465-471, 2023 Jan.
Artigo em Zh | MEDLINE | ID: mdl-36725236

RESUMO

The present study observed the regulatory effect of total flavonoids of Ziziphora clinopodioides on autophagy and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathways in ApoE~(-/-) mice and explored the mechanism of total flavonoids of Z. clinopodioides against atherosclerosis(AS). ApoE~(-/-) mice were fed on a high-fat diet for eight weeks to induce an AS model. The model mice were randomly divided into a model group, a positive control group, and low-, medium-and high-dose groups of total flavonoids of Z. clinopodioides, while C57BL/6J mice fed on a common diet were assigned to the blank group. The serum and aorta samples were collected after intragastric administration for 12 weeks, and the serum levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C), and high density lipoprotein-cholesterol(HDL-C) were detected by an automatic biochemical analyzer. The serum expression levels of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), matrix metalloproteinase-2(MMP-2), and matrix metalloprotei-nase-9(MMP-9) were detected by enzyme-linked immunosorbent assay(ELISA). Oil red O staining was used to observe the aortic plaque area in mice. Hematoxylin-eosin(HE) staining was used to observe the aortic plaque and pathological changes in mice. The expression of P62 and LC3 in the aorta was detected by the immunofluorescence method. The protein expression of LC3Ⅱ/Ⅰ, Beclin-1, P62, p-PI3K, p-Akt, and p-mTOR in the aorta of mice was detected by Western blot. The results showed that compared with the blank group, the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2 and MMP-9 in the model group were significantly increased(P<0.01 or P<0.05), the content of HDL-C was decreased(P<0.05), intra-aortic plaque area was enlarged(P<0.01), the expression of LC3 in the aorta was significantly down-regulated, P62 expression was up-regulated(P<0.01 or P<0.05), the expressions of LC3Ⅱ/Ⅰ and Beclin-1 in the aortic lysate were significantly down-regulated, and the expressions of p-PI3K, p-Akt, p-mTOR and P62 were significantly increased(P<0.01). The medium-and high-dose groups of total flavonoids of Z. clinopodioides could reduce the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2, and MMP-9 in AS model mice(P<0.01 or P<0.05), and increase the content of HDL-C(P<0.01 or P<0.05). The aortic plaque area of mice after middle and high doses of total flavonoids of Z. clinopodioides was significantly reduced(P<0.01), the content of foam cells decrease, and the narrowing of the lumen decreased. The total flavonoids of Z. clinopodioides significantly increased the expression of LC3 in the aorta and the expression of LC3Ⅱ/Ⅰ and Beclin-1 in the lysate, and decreased the expression of P62 in the aorta and the expression of p-PI3K, p-Akt, p-mTOR and P62 in the lysate(P<0.01 or P<0.05). The results showed that the total flavonoids of Z. clinopodioides could improve the content of blood lipids and inflammatory factors, and reduce the generation of foam cells and plaques in aortic tissue, and the mechanism may be related to the regulation of PI3K/Akt/mTOR signaling pathway.


Assuntos
Aterosclerose , Placa Aterosclerótica , Animais , Camundongos , Apolipoproteínas E , Aterosclerose/tratamento farmacológico , Aterosclerose/genética , Proteína Beclina-1 , LDL-Colesterol , Molécula 1 de Adesão Intercelular , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/genética , Molécula 1 de Adesão de Célula Vascular/genética
10.
Mol Cancer ; 21(1): 37, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35130920

RESUMO

PURPOSE: The overall response of cisplatin-based chemotherapy in bladder urothelial carcinoma (BUC) remains unsatisfactory due to the complex pathological subtypes, genomic difference, and drug resistance. The genes that associated with cisplatin resistance remain unclear. Herein, we aimed to identify the cisplatin resistance associated genes in BUC. EXPERIMENTAL DESIGN: The cytotoxicity of cisplatin was evaluated in six bladder cancer cell lines to compare their responses to cisplatin. The T24 cancer cells exhibited the lowest sensitivity to cisplatin and was therefore selected to explore the mechanisms of drug resistance. We performed genome-wide CRISPR screening in T24 cancer cells in vitro, and identified that the gene heterogeneous nuclear ribonucleoprotein U (HNRNPU) was the top candidate gene related to cisplatin resistance. Epigenetic and transcriptional profiles of HNRNPU-depleted cells after cisplatin treatment were analyzed to investigate the relationship between HNRNPU and cisplatin resistance. In vivo experiments were also performed to demonstrate the function of HNRNPU depletion in cisplatin sensitivity. RESULTS: Significant correlation was found between HNRNPU expression level and sensitivity to cisplatin in bladder cancer cell lines. In the high HNRNPU expressing T24 cancer cells, knockout of HNRNPU inhibited cell proliferation, invasion, and migration. In addition, loss of HNRNPU promoted apoptosis and S-phase arrest in the T24 cells treated with cisplatin. Data from The Cancer Genome Atlas (TCGA) demonstrated that HNRNPU expression was significantly higher in tumor tissues than in normal tissues. High HNRNPU level was negatively correlated with patient survival. Transcriptomic profiling analysis showed that knockout of HNRNPU enhanced cisplatin sensitivity by regulating DNA damage repair genes. Furthermore, it was found that HNRNPU regulates chemosensitivity by affecting the expression of neurofibromin 1 (NF1). CONCLUSIONS: Our study demonstrated that HNRNPU expression is associated with cisplatin sensitivity in bladder urothelial carcinoma cells. Inhibition of HNRNPU could be a potential therapy for cisplatin-resistant bladder cancer.


Assuntos
Antineoplásicos , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Carcinoma de Células de Transição/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo U , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
11.
Opt Express ; 30(2): 2131-2142, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35209360

RESUMO

In many integrated optics systems, grating couplers are a key component of interfacing the external light source with in-plane photonic devices. Grating couplers with dual-band capability are often desired for expanding the operation spectrum of photonic systems. Here, we propose and theoretically investigate, for the first time, a 4.95 µm-8.5 µm dual-band grating coupler on a Ge-on-SOI platform. In addition to conventional structures, Bragg gratings are introduced to two wavelength division directions for crosstalk suppression. With this design, the simulated coupling efficiencies have respectively reached 59.93% and 46.38% for the 4.95 µm and 8.5 µm bands. This mid-infrared dual-band grating coupler may be useful for defense and environmental monitoring applications.

12.
Opt Express ; 30(4): 4692-4705, 2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35209445

RESUMO

In digital micromirror device (DMD)-based projection photolithography, the throughput largely depends on the effectiveness of the laser energy utilization, which is directly correlated to the diffraction efficiency of DMD. Here, to optimize the DMD diffraction efficiency and thus the laser energy utilization, we calculate the diffraction efficiencies Ediffraction of DMD with various pitch sizes at wavelengths ranging from 200 nm to 800 nm, using the two-dimensional blazed grating diffraction theory. Specifically, the light incident angle is optimized for 343 nm laser and 7.56 µm pitch-size DMD, and the maximum single-order diffraction efficiency Ediffraction is increased from 40% to 96%. Experimentally, we use the effective energy utilization ηeff = Ediffraction,(m,n)/Σ[Ediffraction,(m,n)] at the entrance pupil plane of the objective to verify the effectiveness of the optimized illumination angle in a lithography illumination system with parallel beams of two wavelengths (343 nm and 515 nm). The ηeff of a "blaze" order at a 34° angle of incidence can be optimized up to 88%. The experimental results are consistent with the tendency of the calculated results, indicating that this optimization model can be used to improve the energy utilization of projection lithography with the arbitrarily designable wavelengths and the DMD's pitch size.

13.
Opt Express ; 30(25): 45312-45326, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36522939

RESUMO

Neural network-based inverse lithography technology (NNILT) has been used to improve the computational efficiency of large-scale mask optimization for advanced photolithography. NNILT is now mostly based on labels, and its performance is affected by the quality of labels. It is difficult for NNILT to achieve high performance and extrapolation ability for mask optimization without using labels. Here, we propose a label-free NNILT (LF-NNILT), which is implemented completely without labels and greatly improves the printability of the target layouts and the manufacturability of the synthesized masks compared to the traditional ILT. More importantly, the optimization speed of LF-NNILT is two orders of magnitude faster than the traditional ILT. Furthermore, LF-NNILT is simpler to implement and can achieve better solvers to support the development of advanced lithography.


Assuntos
Redes Neurais de Computação , Impressão , Tecnologia
14.
Opt Express ; 30(20): 36791-36801, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36258601

RESUMO

Maskless lithography technologies have been developed and played an important role in the fabrication of functional micronano devices for microelectronics, biochips and photonics. Optical projection lithography based on digital micromirror device (DMD) is an efficient maskless lithography technology that can rapidly fabricate complex structures. The precise modulation of gap width by DMD maskless optical projection lithography (MOPL) using femtosecond laser becomes important for achieving micronano structures. Herein, we have investigated the relationship between the structure morphology and the light intensity distribution at the image plane by multi-slit diffraction model and Abbe imaging principle, and optimized the gap width more accurately by modulating exposure energy. The aperture diameter of the objective lens has a substantial effect on the pattern consistency. The continuously adjustable structural gap widths of 2144 nm, 2158 nm and 1703 nm corresponding to 6, 12, 24 pixels are obtained by varying the exposure energy in the home-built MOPL system. However, the ideal gap structure cannot be obtained only by adjusting the exposure energy when the gap width is small, such as 1 or 2 pixels. Furthermore, we have proposed an alternative way to achieve fine gap structures through the structural decomposition design and precise control of exposure energy in different regions without changing the MOPL optical system. This study would provide a promising protocol for fabricating gap microstructures with controllable configuration using MOPL technique.

15.
Cancer Cell Int ; 22(1): 128, 2022 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-35305624

RESUMO

BACKGROUND: While the correlation between PD-L1 expression and KRAS mutation has been previously reported in other solid tumors such as non-small cell lung cancer (NSCLC), whether PD-L1 can be modulated by ERK signaling downstream of KRAS in intrahepatic cholangiocarcinoma (iCCA) and the underlying molecular regulatory mechanism remain unclear. METHODS: The expression of ERK, p-ERK, PD-L1 and autophagy markers following KRAS knockdown or Ras/Raf/MEK/ERK signaling inhibitors treatment was examined in two human iCCA cell lines (HuCCT1 and RBE) using western blotting and immunofluorescence. Both pharmacological autophagy inhibitors and short-interfering RNA against ATG7 were applied to inhibit autophagy. The apoptosis rates of iCCA cell lines were detected by flow cytometry and CCK-8 after co-culturing with CD3/CD28-activated human CD8+ T lymphocytes. Immunohistochemistry was applied to detect the correlation of ERK, p-ERK and PD-L1 in 92 iCCA tissues. RESULTS: The present study demonstrated that the PD-L1 expression level was distinctly reduced in KRAS-mutated iCCA cell lines when ERK signaling was inhibited and ERK phosphorylation levels were lowered. The positive association between p-ERK and PD-L1 was also verified in 92 iCCA tissue samples. Moreover, ERK inhibition induced autophagy activation. Both inhibiting autophagy via autophagy inhibitors and genetically silencing the ATG7 expression partially reversed the reduced PD-L1 expression caused by ERK inhibition. In addition, ERK-mediated down-regulation of PD-L1 via autophagy pathways induced the apoptosis of iCCA cells when co-cultured with CD3/CD28-activated human CD8+ T lymphocytes in vitro. CONCLUSIONS: Our results suggest that ERK signaling inhibition contributes to the reduction of PD-L1 expression through the autophagy pathway in iCCA. As a supplement to anti-PD-1/PD-L1 immunotherapy, ERK-targeted therapy may serve as a potentially novel treatment strategy for human KRAS-mutated iCCA.

16.
Surg Endosc ; 36(2): 1394-1406, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33782758

RESUMO

BACKGROUND: Due to technical challenges, single-site endoscopic thyroidectomy (SSET) is seldom reported and has been attempted in only limited cases. This large-scale study aimed to compare the clinical outcomes of standardized transareola SSET (TASSET) with those of conventional open thyroidectomy (COT) for thyroid cancer. METHODS: The data were prospectively collected, and case-match study was performed at a ratio of 1:1 according to age, sex, body mass index, lesion size, number of lesion foci, lesion side, recurrent laryngeal nerve (RLN) exploration and pathology. Two hundred eligible patients underwent TASSET, and the same number of patients was selected for propensity score matching from 2256 patients who underwent COT. Perioperative data, including surgical profile, oncological and traumatic burdens, and cosmetic satisfaction, were analyzed. RESULTS: No significant differences were observed in blood loss or drainage between TASSET and COT groups. There were no differences in operation time between TASSET and COT (106.39 ± 28.44 vs 102.55 ± 23.10 min, p = 0.154). A total of 3.63 ± 1.82 lymph nodes (LNs) were retrieved from CND with 0.96 ± 1.42 positive in TASSET. In COT, the total and positive LN yields were 3.77 ± 1.91 and 0.99 ± 1.40 (p = 0.445, p = 0.802). Cancer recurrence was not observed in either group. There were no differences in the occurrence of permanent and transient hoarseness or RLN injuries. Postoperative flap seroma or hematoma occurred in 12 TASSET patients and 58 COT patients (p < 0.001). The pain score, CRP level and ESR in TASSET group were lower than those in COT group. TASSET yielded significantly better incision recovery and cosmetic scores than did COT at both the proliferation and stabilization stages. CONCLUSIONS: TASSET is technically feasible and yields enhanced recovery with minimally invasive and cosmetic advantages without compromising the level of safety or cancer eradication.


Assuntos
Neoplasias da Glândula Tireoide , Tireoidectomia , Endoscopia/métodos , Humanos , Recidiva Local de Neoplasia/cirurgia , Duração da Cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos
17.
J Craniofac Surg ; 33(7): 2059-2062, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37771105

RESUMO

BACKGROUND: Ossifying fibroma is one of the common benign tumors that affect the appearance and functions of the jaw. Ossifying fibroma may exhibit a wide range of biological behaviors, leading to deformities involving the jaw and other secondary facial deformities. Hence, to improve the function of the jaw and the patient's general facial appearance (bearing in mind each patient's facial shape and, or appearance), the authors thus, however, used a ''one and a half"-barrel fibular bone graft to achieve the ideal height and radian of the bone graft. CASE PRESENTATION: Between July 2017 and January 2021, the authors retrospectively collected and analyzed clinical and surgical data from 39 patients who had undergone operations in our hospital. Twenty patients were operated on using our new surgical method, whereas 19 patients received conventional or debulking operation. Clinical factors associated with the operation were assessed, including classification of the jaw defects, perioperative complications, and postoperative outcomes. RESULTS: All the flaps ultimately survived. According to the postoperative satisfaction survey, patients who underwent reconstruction were satisfied with their postoperative facial appearance, with an average of 8.5 out of 10. Based on the preoperative clinical data, 26 patients had suitable bone grafts for dentures to improve their oral function. CONCLUSIONS: A ''one and a half''-barrel fibular bone graft effectively improves the facial appearance of patients and as well as provides an appropriate height and radian for the bone graft.


Assuntos
Fibroma Ossificante , Procedimentos de Cirurgia Plástica , Neoplasias Cranianas , Humanos , Fibroma Ossificante/cirurgia , Estudos Retrospectivos , Retalhos Cirúrgicos/cirurgia , Fíbula/transplante , Neoplasias Cranianas/cirurgia , Transplante Ósseo/métodos
18.
Nano Lett ; 21(9): 3915-3921, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33938760

RESUMO

The emerging demand for device miniaturization and integration prompts the patterning technique of micronano-cross-scale structures as an urgent desire. Lithography, as a sufficient patterning technique, has been playing an important role in achieving functional micronanoscale structures for decades. As a promising alternative, we have proposed and demonstrated the maskless optical projection nanolithography (MLOP-NL) technique for efficient cross-scale patterning. A minimum feature size of 32 nm, which is λ/12 super resolution breaking the optical diffraction limit, has been achieved by a single exposure. Furthermore, multiscale two-dimensional micronano-hybrid structures with the size over hundreds of micrometers and the precision at tens of nanometers have been fabricated by simply controlling the exposure conditions. The proposed MLOP-NL technique provides a powerful tool for achieving cross-scale patterning with both large-scale and precise configuration with high efficiency, which can be potentially used in the fabrication of multiscale integrated microsystems.


Assuntos
Impressão
19.
J Environ Manage ; 316: 115233, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35561497

RESUMO

Studies on the environmental impacts of China-African trade relations are scarce. To fill the gap, this research examines the effects of Sino-African trade relations on carbon dioxide (CO2) emissions intensity in Africa, employing panel quantile regression for 39 African countries over the period of 1992-2015. The results indicate that imports have a negative and significant effect on CO2 emissions intensity across all quantile distributions, whereas exports have a positive and significant effect, except at the 25th and 35th quantiles. The findings also confirm the inverted U-shaped environmental Kuznets curve hypothesis, particularly for countries at higher emissions points. The study also demonstrates that urbanisation and energy intensity positively affect CO2 intensity, while the effect of foreign direct investment is negative and significant, confirming the pollution halo hypothesis. Finally, policy implications are presented based on the findings of the study.


Assuntos
Dióxido de Carbono , Desenvolvimento Econômico , África , Dióxido de Carbono/análise , Investimentos em Saúde , Urbanização
20.
Plant Cell ; 30(5): 1100-1118, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29581216

RESUMO

Salt stress can significantly affect plant growth and agricultural productivity. Receptor-like kinases (RLKs) are believed to play essential roles in plant growth, development, and responses to abiotic stresses. Here, we identify a receptor-like cytoplasmic kinase, salt tolerance receptor-like cytoplasmic kinase 1 (STRK1), from rice (Oryza sativa) that positively regulates salt and oxidative stress tolerance. Our results show that STRK1 anchors and interacts with CatC at the plasma membrane via palmitoylation. CatC is phosphorylated mainly at Tyr-210 and is activated by STRK1. The phosphorylation mimic form CatCY210D exhibits higher catalase activity both in vitro and in planta, and salt stress enhances STRK1-mediated tyrosine phosphorylation on CatC. Compared with wild-type plants, STRK1-overexpressing plants exhibited higher catalase activity and lower accumulation of H2O2 as well as higher tolerance to salt and oxidative stress. Our findings demonstrate that STRK1 improves salt and oxidative tolerance by phosphorylating and activating CatC and thereby regulating H2O2 homeostasis. Moreover, overexpression of STRK1 in rice not only improved growth at the seedling stage but also markedly limited the grain yield loss under salt stress conditions. Together, these results offer an opportunity to improve rice grain yield under salt stress.


Assuntos
Oryza/metabolismo , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Regulação da Expressão Gênica de Plantas , Peróxido de Hidrogênio/metabolismo , Oryza/genética , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia , Fosforilação , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética , Estresse Fisiológico
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