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Gene fusions can drive tumor development for multiple types of cancer. Currently, many drugs targeting gene fusions are being approved for clinical application. At present, tyrosine receptor kinase (TRK) inhibitors targeting neurotrophic tyrosine receptor kinase (NTRK) gene fusions are among the first "tumor agnostic" drugs approved for pan-cancer use. Representative TRK inhibitors, including larotrectinib and entrectinib, have shown high efficacy for many types of cancer. At the same time, several second-generation drugs designed to overcome first-generation drug resistance are undergoing clinical development. Due to the rarity of NTRK gene fusions in common cancer types and technical issues regarding the complexity of fusion patterns, effectively screening patients for TRK inhibitor treatment in routine clinical practice is challenging. Different detection methods including immunohistochemistry, fluorescence in situ hybridization, reverse transcription-polymerase chain reaction, and (DNA and/or RNA-based) next-generation sequencing have pros and cons. As such, recommending suitable tests for individual patients and ensuring the quality of tests is essential. Moreover, at present, there is a lack of systematic review for the clinical efficacy and development status of first- and second-generation TRK inhibitors. To resolve the above issues, our expert group has reached a consensus regarding the diagnosis and treatment of NTRK gene fusion solid tumors, aiming to standardize clinical practice with the goal of benefiting patients with NTRK gene fusions treated with TRK inhibitors.

Vascular endothelium dysfunction plays an important role in oncological and pulmonary diseases. Endothelial barrier dysfunction is the initial step of pulmonary vascular remodeling (PVR) and pulmonary arterial hypertension. Upregulation of a pro-autophagy protein Atg101 in the endothelial cells triggered a cascade of intracellular events that leads to endothelial dysfunction through apoptosis. Herein, we proposed a strategy that used endothelial targeting DNA nanostructures to deliver Atg101 siRNA (siAtg101) as a safe, biocompatible "band-aid" to restore pulmonary arterial endothelial barrier integrity within the intricate milieu of pulmonary cells and the pulmonary vasculature. The siAtg101 and aptamer conjugated DNA nanostructures were found to attenuate hypoxia-induced pulmonary endothelial leakiness with surprisingly high selectivity and efficacy. Further

Human epidermal growth factor receptor 2 (HER2) possesses tyrosine kinase activity and participates in cell growth, differentiation and migration, and survival. Its alterations, mainly including mutations, amplifications, and overexpression are associated with poor prognosis and are one of the major drivers in non-small cell lung cancer (NSCLC). Several clinical trials had been investigating on the treatments of HER2-altered NSCLC, including conventional chemotherapy, programmed death 1 (PD-1) inhibitors, tyrosine kinase inhibitors (TKIs) and antibody-drug conjugates (ADCs), however, the results were either disappointing or encouraging, but inconsistent. Trastuzumab deruxtecan (T-DXd) was recently approved by the Food and Drug Administration as the first targeted agent for treating HER2-mutant NSCLC. Effective screening of patients is the key to the clinical application of HER2-targeted agents such as TKIs and ADCs. Various testing methods are nowadays available, including polymerase chain reaction (PCR), next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), etc. Each method has its pros and cons and should be reasonably assigned to appropriate patients for diagnosis and guiding treatment decisions. To help standardize the clinical workflow, our expert group reached a consensus on the clinical management of HER2-altered NSCLC, focusing on the diagnosis and treatment strategies.

Herein, a strategy is proposed to simultaneously deliver the small-molecule drug metformin and siRNA with self-assembled DNA nanostructures. The biomedical application of DNA nanostructures is highly promising but still in its infancy. DNA nanostructures as drug delivery vehicles are conventionally synthesized in a magnesium-containing buffer. We propose using an anticancer drug to assemble DNA nanostructures and deliver them with siRNA for synergistic anticancer therapy. The metformin cargo induces DNA self-assembly into well-defined, uniform nanostructures, producing a drug–DNA nanocomplex with multiple functionalities for cancer therapy. Both tile-based and DNA origami structures can be assembled with metformin. The as-prepared metformin/DNA nanocomplex showed high structural and thermal stability and enzymatic resistance in physiological settings. The metformin in the nanocomplex and the KRASG12C siRNA exerted a strong, synergistic antitumor effect against KRAS-mutated non-small cell lung cancer (NSCLC) both in vitro and in vivo by suppressing the RAS/AKT/mTOR and AMPK/AKT/mTOR signaling pathways. The current study suggests that the assembly of complex DNA nanomaterials with carefully chosen small molecules is key to endowing DNA nanostructures with new functionalities and subsequently expanding their applications in multidisciplinary research fields.

Complexing self-assembled DNA nanostructures with various functional guest species is the key to unlocking new and exciting biomedical applications. Cationic guest species not only induce magnesium-free DNA to self-assemble into defined structures but also endow the final complex nanomaterials with new properties. Herein, we propose a novel strategy that employs naturally occurring cationic amino acids to induce DNA self-assembly into defined nanostructures. Natural l-arginine and l-lysine can readily induce the assembly of tile-based DNA nanotubes and DNA origami sheets in a magnesium-free manner. The self-assembly processes are demonstrated to be pH- and concentration-dependent and are achieved at constant temperatures. Moreover, the assembled DNA/amino acid complex nanomaterials are stable at a physiological temperature of 37 °C. Substituting l-arginine with its D form enhances its serum stability. Further preliminary examination of this complex nanomaterial platform for biomedical applications indicates that DNA/amino acids exhibit distinct cellular uptake behaviors compared with their magnesium-assembled counterparts. The nanomaterial mainly clusters around the cell membrane and might be utilized to manipulate molecular events on the membrane. Our study suggests that the properties of DNA nanostructures can be tuned by complexing them with customized guest molecules for a designed application. The strategy proposed herein might be promising to advance the biomedical applications of DNA nanostructures., Graphical abstract Image 1, Highlights • A “noncanonical DNA self-assembly” strategy is proposed. • Cationic amino acids can assemble DNA nanostructures in a magnesium-free system. • The complex nanomaterial exhibited high structural and serum stability. • DNA nanostructures can be engineered with customized guest molecules for multiple applications.

Pulmonary artery vascular endothelial dysfunction plays a pivotal role in the occurrence and progression of pulmonary vascular remodeling (PVR). To address this, aberrantly expressed non-coding microRNAs (miRNAs) are excellent therapeutic targets in human pulmonary artery endothelial cells (HPAECs). Here, we discovered and validated the overexpression of miRNA-152 in HPAECs under hypoxia and its role in endothelial cell dysfunction. We constructed a framework nucleic acid nanostructure that harbors six protruding single-stranded DNA segments that can fully hybridize with miRNA-152 (DNT-152). DNT-152 was efficiently taken up by HPAECs with increasing time and concentration; it markedly induced apoptosis, and inhibited HPAEC growth under hypoxic conditions. Mechanistically, DNT-152 silenced miRNA-152 expression and upregulated its target gene Meox2, which subsequently inhibited the AKT/mTOR signaling pathway. These results indicate that miRNA-152 in HPAECs may be an excellent therapeutic target against PVR, and that framework nucleic acids with carefully designed sequences are promising nanomedicines for noncancerous cells and diseases.

Micro-milling is a low-cost, efficient, and high-precision machining method for manufacturing tiny parts, and has significant application value in various fields. In order to meet the high-accuracy requirements, several composite micro-milling methods have been proposed. However, these methods cannot change surface characteristics of materials, and poor permeability of cooling medium on the tool-workpiece interface remains unsolved. Atmospheric pressure plasma jet can efficiently improve surface wettability without obviously changing surface microstructures and may have promising application potential in machining of difficult-to-cut materials. Here, we propose to induce atmospheric pressure plasma jet to the micro-milling area to improve machinability and surface quality of TC4 titanium alloy. The influences of plasma jet on material wettability and mechanical property are firstly investigated by conducting plasma modification and tensile experiments. Then, micro-milling experiments of TC4 titanium alloy are performed under different atmospheres (dry, nitrogen jet, plasma jet, minimum quantity lubrication, and plasma jet + minimum quantity lubrication). The experimental results indicate that plasma jet can promote material fracture of TC4 titanium alloy, as well as reduce cutting force and cutting temperature, thereby obtaining better surface quality.

Designing and building artificial nanodevices and nanoarchitectures in living systems are extremely intriguing subjects in nanotechnology and synthetic biology. Taking advantage of cellular machinery and endogenous biomacromolecules, such as proteins, is key to achieving the precise and sophisticated manipulation of nanoarchitectures. In this study, we proposed a protein-mediated DNA self-assembly strategy in a molecular crowding environment. By carefully controlling the surface charge of basic nuclear proteins in a crowding environment that mimicked the intracellular environment, we demonstrated that highly positively charged protamine can assemble individual DNA strands into defined structures similar to a catalytic process manner. Successful self-assembly required an optimized protamine surface charge and a crowding environment; otherwise, this self-assembly was impossible. Polyacrylamide gel electrophoresis (PAGE), atomic force microscopy (AFM), and dynamic light scattering (DLS) results showed that tile-based DNA tubular structures, tetrahedra, and two dimensional DNA origami structures were successfully assembled. We inferred that the assembly process occurred between the arginine-rich domain of protamine and DNA strands that repeatedly interacted with each other in the viscous system. The current study provides a potential strategy to construct nanodevices in living systems and presents an alternative protein-DNA interaction for the potential fabrication of protein-DNA hybrid nanomaterials.

Treatment with the Toll‑like receptor 7 (TLR7) agonist, resiquimod (R848), is effective in various types of cancer, such as breast, pancreatic and colorectal cancer. The reported antitumor effect of R848 in lung cancer is considered to be achieved by targeting macrophages. In the present study, it was demonstrated that TLR7 expression on various immune cell types initially rises, then declines in the late stage of lung cancer. Intraperitoneal injection of R848 resulted in a reduction in tumor burden and prolonged survival in both subcutaneous and metastatic lung cancer models in C57BL/6 mice. Initial treatment with R848 at an early stage was found to be the optimal choice. Systemic injection of R848 promoted the activation of innate and adaptive immune responses. Systemic administration of R848 upregulated TLR7 expression in dendritic cells (DCs) and enhanced the activation of DCs and natural killer (NK) cells. Moreover, this treatment also resulted in increased production of T helper cell‑associated cytokines in serum, including IFN‑γ, TNF‑α and IL‑2. In addition, continuous treatment with R848 increased the proportion of DCs, NK and CD8

In order to solve the problem of low efficiency and high cost in designing inserts with groove, finite element simulation (FEM) method has been employed to directly simulate the chip breaking condition. However, the current methods tend to involve a large number of cutting experiments and a user subroutine program used for secondary development, causing inconveniency in engineering application. Here, we propose a high-efficient three-dimensional (3D) FEM method to analyze the chip breakage properties of complicate-grooved insert. For the simulation, a three-dimensional cutting simulation model is established by Deform 3D FE package, and the Johnson-Cook (J-C) material constitutive model and Cockcroft-Latham (C-L) ductile fracture criterion are adopted. To verify the validity of the model, the simulations and corresponding turning experiments of AISI 1045 steel are performed with complicate-grooved insert at several combination groups of cutting depth and feed rate. The estimated chip morphology, chip breaking process, and cutting force from the simulation are in good consistency with those from the experiments. Additionally, the comparisons between the simulations and corresponding turning experiments with complicate-grooved insert and flat rake insert are conducted. The results show that the chip breaking groove can significantly change the chip flow angle and the chip geometry and that the complicate-grooved insert can more efficiently promote chip breakage than the flat rake insert. Therefore, the 3D FEM method proposed can be used to effectively investigate the chip formation mechanism and chip breakage properties and has promising application prospects in complicate-grooved insert design and cutting parameter optimization.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a condition with an imbalanced inflammatory response and delayed resolution of inflammation. Macrophage polarization plays an important role in inflammation and resolution. However, the mechanism of macrophage polarization in ALI/ARDS is not fully understood. We found that mice with lipopolysaccharide administration developed lung injury with the accumulation of extracellular cold-inducible RNA-binding protein (eCIRP) in the lungs. eCIRP, as a damage-associated molecular pattern (DAMP), inhibited M2 macrophage polarization, thereby tipping the balance toward inflammation rather than resolution. Anti-CIRP antibodies reversed such phenotypes. The levels of macrophage erythropoietin (EPO) receptor (EPOR) were reduced after eCIRP treatment. Myeloid-specific EPOR-deficient mice displayed restrained M2 macrophage polarization and impaired inflammation resolution. Mechanistically, eCIRP impaired Rab26, a member of Ras superfamilies of small G proteins, and reduced the transportation of surface EPOR, which resulted in macrophage polarization toward the M1 phenotype. Moreover, EPO treatment hardly promotes M2 polarization in Rab26 knockout (KO) macrophages through EPOR. Collectively, macrophage EPOR signaling is impaired by eCIRP through Rab26 during ALI/ARDS, leading to the restrained M2 macrophage polarization and delayed inflammation resolution. These findings identify a mechanism of persistent inflammation and a potential therapy during ALI/ARDS.

High-mobility group box 1 (HMGB1) protein can impair phagocyte function by suppressing the macrophage-mediated clearance of apoptotic cells (ACs), thereby delaying inflammation resolution in the lungs and allowing the progression of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, the precise mechanism underlying this HMGB1-mediated inhibition of efferocytosis remains unknown. The aim of this study was to determine the effect of HMGB1 on macrophage-mediated efferocytosis. We discovered that HMGB1 prevented efferocytosis by bone marrow-derived macrophages (BMDMs) and suppressed the expression of Ras-related GTP-binding protein 43 (Rab43), a member of the Ras-associated binding (Rab) family. The downregulation of Rab43 expression resulted in impaired clearance of apoptotic thymocytes by BMDMs. Subsequent analysis of HMGB1-treated and Rab43-deficient BMDMs revealed the inhibited transport of cluster of differentiation 91 (CD91), a phagocyte recognition receptor, from the cytoplasm to the cell surface. Notably, Rab43 directly interacted with CD91 to mediate its intercellular trafficking. Furthermore, Rab43 knockout delayed the inflammation resolution and aggravated the lung tissue damage in mice with ALI. Therefore, our results provide evidence that HMGB1 impairs macrophage-mediated efferocytosis and delays inflammation resolution by suppressing the Rab43-regulated anterograde transport of CD91, suggesting that the restoration of Rab43 levels is a promising strategy for attenuating ALI and ARDS in humans.

Nickel-based superalloy Inconel 718 is one of the hardest materials owing to its high hardness and additional physical properties. It is the most commonly used superalloy in gas turbine, aerospace, and automobile sectors. Micro-milling is generally employed for precision manufacturing of tiny structures, but it is difficult to obtain good surface quality with micro-milling Inconel 718 because of its excellent mechanical properties like high strength and hardness. Atmospheric pressure cold plasma jet can effectively improve surface wettability without changing surface micromorphology, which is expected to have positive lubricating effects in micro-machining of difficult-to-cut materials. In addition, minimum quantity lubrication can induce coolants into the machining area more efficiently, and is especially appropriate for micro-machining. In this paper, we propose a composite micro-milling method combining plasma jet and minimum quantity lubrication to machine Inconel 718. The effect of plasma jet on machinability is investigated by performing micro-milling experiments under different atmospheres (dry, nitrogen jet, plasma jet, minimum quantity lubrication, and plasma + minimum quantity lubrication). Surface roughness, cutting forces, and residual stress are the measures using corresponding techniques. The results indicate that the atmospheric pressure cold plasma jet can efficiently improve surface quality and reduce cutting forces of Inconel 718.

Achieving diverse colours in superhydrophobic surfaces is of interest in academic research and industrial applications. The current methods used to prepare coloured surfaces tend to be complicated, expensive or difficult to control the coloured areas and tune the colours. The study reports an efficient and low-cost electrolytic colouring method for the preparation of robust coloured superhydrophobic Al surfaces. The surfaces are firstly electrochemically etched and anodised before electrolytic colouring is performed. Colours of the superhydrophobic surfaces can be easily tuned by adjusting the anodisation time, and the colouring areas can be well controlled with the combination of mask technology. The corrosion behaviour and abrasion resistance of the coloured superhydrophobic surfaces are characterised by polarisation curves and abrasion tests. The results demonstrate that the coloured superhydrophobic surfaces possess excellent corrosion and abrasion resistances, indicating their application potential in industrial fields.

Objective. Coronavirus disease 2019 (COVID-19) is a considerable global public health threat. This study sought to investigate whether blood glucose (BG) levels or comorbid diabetes are associated with inflammatory status and disease severity in patients with COVID-19. Methods. In this retrospective cohort study, the clinical and biochemical characteristics of COVID-19 patients with or without diabetes were compared. The relationship among severity of COVID-19, inflammatory status, and diabetes or hyperglycemia was analyzed. The severity of COVID-19 in all patients was determined according to the diagnostic and treatment guidelines issued by the Chinese National Health Committee (7th edition). Results. Four hundred and sixty-one patients were enrolled in our study, and 71.58% of patients with diabetes and 13.03% of patients without diabetes had hyperglycemia. Compared with patients without diabetes ( n = 366 ), patients with diabetes ( n = 95 ) had a higher leucocyte count, neutrophil count, neutrophil to lymphocyte ratio (NLR), and erythrocyte sedimentation rate (ESR). There was no association between severity of COVID-19 and known diabetes adjusted for age, sex, body mass index (BMI), known hypertension, and coronary heart disease. The leucocyte count, NLR, and C-reactive protein (CRP) level increased with increasing BG level. Hyperglycemia was an independent predictor of critical (OR 4.00, 95% CI 1.72-9.30) or severe (OR 3.55, 95% CI 1.47-8.58) COVID-19, and of increased inflammatory levels (high leucocyte count (OR 4.26, 95% CI 1.65-10.97), NLR (OR 2.76, 95% CI 1.24-6.10), and CRP level (OR 2.49, 95% CI 1.19-5.23)), after adjustment for age, sex, BMI, severity of illness, and known diabetes. Conclusion. Hyperglycemia was positively correlated with higher inflammation levels and more severe illness, and it is a risk factor for the increased severity of COVID-19. The initial measurement of plasma glucose levels after hospitalization may help identify a subset of patients who are predisposed to a worse clinical course.

Background and aims: Asthma–chronic obstructive pulmonary disease (COPD) overlap (ACO) is poorly recognized in China. Our study determined the distribution of ACO and its clinical characteristics among patients (aged ⩾40 years) with airflow limitation at Chinese tertiary hospitals. Methods: This cross-sectional, non-interventional study (NCT02600221), conducted between December 2015 and October 2016 in 20 Tier-3 Chinese hospitals, included patients aged ⩾40 years with post-bronchodilator (BD) FEV1/FVC 1/FVC) Results: In 2003 patients (mean age 62.30 ± 9.86 years), distribution of ACO, COPD and asthma were 37.40%, 48.50% and 14.10%, respectively. Proportions of patients with A, B, C and D grouping were 11.70%, 31.00%, 6.90% and 50.30% as per GOLD 2017, whereas they were 15.10%, 51.10%, 3.60% and 30.20% as per GOLD 2015. Similar clinical symptoms were reported in all three groups. A higher percentage of ACO patients presented with dyspnea, wheezing and chest tightness. Compared with the COPD group, a greater proportion of ACO patients reported wheezing (74.6% and 65.40%), while a lower proportion in the ACO group reported cough (79.40% versus 82.70%) and expectoration (76.50% versus 81.60%). Blood eosinophil count ⩾0.3 × 109/L was observed in 34.6% of ACO patients. The clinical recognition rate of ACO was 31.4%. Conclusion: Despite ACO affecting two-fifths of the study population, the initial diagnosis rate was low at 6% in China, thus warranting concerted efforts to improve ACO diagnosis. ClinicalTrials.gov: [ClinicalTrials.gov identifier: NCT02600221] registered 22 October 2015, https://clinicaltrials.gov/ct2/show/NCT02600221 The reviews of this paper are available via the supplemental material section.

Supplemental material, Author_Response_1_1 for Current situation of asthma–COPD overlap in Chinese patients older than 40 years with airflow limitation: a multicenter, cross-sectional, non-interventional study by Jian Kang, Jinping Zheng, Baiqiang Cai, Fuqiang Wen, Wanzhen Yao, Xiaoju Zhang, Yan Chen, Guansong Wang, Wen Li and Jie Cao in Therapeutic Advances in Respiratory Disease

Supplemental material, Supplementary_Tables for Current situation of asthma–COPD overlap in Chinese patients older than 40 years with airflow limitation: a multicenter, cross-sectional, non-interventional study by Jian Kang, Jinping Zheng, Baiqiang Cai, Fuqiang Wen, Wanzhen Yao, Xiaoju Zhang, Yan Chen, Guansong Wang, Wen Li and Jie Cao in Therapeutic Advances in Respiratory Disease

Supplemental material, Reviewer_1,_v.1 for Current situation of asthma–COPD overlap in Chinese patients older than 40 years with airflow limitation: a multicenter, cross-sectional, non-interventional study by Jian Kang, Jinping Zheng, Baiqiang Cai, Fuqiang Wen, Wanzhen Yao, Xiaoju Zhang, Yan Chen, Guansong Wang, Wen Li and Jie Cao in Therapeutic Advances in Respiratory Disease

Programmable DNA nanostructure self-assembly offers great potentials in nanomedicine, drug delivery, biosensing, and bioimaging. However, due to the intrinsically negatively charged DNA backbones, the instability of DNA nanostructures in physiological settings poses serious challenges to their practical applications. To overcome this challenge, a strategy that combines the magnesium-free DNA self-assembly and functionalization is proposed in this study. We hypothesize that naturally abundant spermidine may not only mediate the self-assembly of DNA nanostructures, but also shield them from harsh physiological environments. As a proof of concept, a DNA nanoprism is designed and synthesized successfully through spermidine. It is found that spermidine can mediate the isothermal self-assembly of DNA nanoprisms. Compared to conventional Mg2+-assembled DNA nanostructures, the spermidine-DNA nanoprism complex shows higher thermal stability and better enzymatic resistance than Mg2+-assembled DNA nanoprisms, and more importantly, it has a much higher cellular uptake efficacy in multiple cancerous cell lines. The internalization mechanism is identified as clathrin-mediated endocytosis. To demonstrate the suitability of this new nanomaterial for biomedical applications, an mTOR siRNA, after being conjugated into the complex, is efficiently delivered into cancer cells and shows excellent gene knockdown efficacy and anticancer capability. These findings indicate that the spermidine-DNA complex nanomaterials might be a promising platform for biomedical applications in the future.

Superhydrophobic surfaces with hydrophilic patterns have great application potential in various fields, such as microfluidic systems and water harvesting. However, many reported preparation methods involve complicated devices and/or masks, making fabrication of these patterned surfaces time-consuming and inefficient. Here, we propose a highly efficient, simple, and maskless microplasma jet (MPJ) treatment method to prepare hydrophilic patterns such as dots, lines, and curves on superhydrophobic aluminum substrates. Contact angles, sliding angles, adhesive forces, and droplet impact behavior of the created patterns are investigated and analyzed. The prepared "dot" patterns exhibit great water adhesion, whereas the "line" patterns show anisotropic adhesion. Additionally, the MPJ treatment does not obviously change the surface structures, which makes it possible to achieve repeatable patterning on one substrate. The adhesion behavior of these patterns could be adjusted using MPJs with different diameters. MPJs with larger diameters are efficient for the creation of patterns with high water adhesion, which can be potentially used for open-channel lab-on-chip systems (e.g., continuous water transportation), whereas MPJs with smaller diameters are preferable in preparing patterns with low water adhesion for diverse applications in biomedical fields (e.g., lossless liquid droplet mixing and cell screening).

Water wettability patterns on superhydrophobic surfaces have been widely designed to meet requirements of many fields, such as lab-on-a-chip devices and bioengineering. However, these systems are easily invalidated by oily liquids. Therefore, oil wettability patterns, which have rarely been focused on, are urgently needed. In this work, the authors successfully control oil wettability of superoleophobic surface by an atmospheric pressure dielectric barrier discharge (DBD) plasma jet. The results indicate that oil wettability is strongly influenced by treatment time, applied voltage and distance between plasma jet outlet and samples. They find that superoleophobic surfaces can be modified to be superoleophilic within 15 s, and that small holes can be etched on the surfaces under high applied voltages. Then, superoleophobic-superoleophilic patterns are prepared via selective plasma jet irradiation on superoleophobic surfaces, and both directional and antigravity transport of water and oily liquids are thus realised without external electrical or magnetic field. Additionally, ageing experiments show that the plasma-treated areas can maintain the induced wettability for >30 days storing under normal ambients, demonstrating superior time stability. The results presented here show the potential of atmospheric pressure DBD plasma jet for rapid oil wettability control and fabrication of long-time-effective oil wettability patterns.

Autophagy plays a key role in pulmonary vascular remodeling via regulation of apoptosis and hyperproliferation of pulmonary arterial endothelial cells, which are the subject of increased attention. Autophagy-related 101 (ATG101) is an essential gene for the initiation of autophagy. Although the structure of ATG101 has been well-characterized, its exact biological function in autophagy is still unknown. In this study, an ATG101 single-stranded antisense RNA-loaded DNA triangular nanoparticle (ssATG101-TNP) is constructed to knock down the ATG101 gene expression. ssATG101-TNP can be effectively transfected into human pulmonary arterial endothelial cells (HPAECs) in time- and dose-dependent manners. Knockdown of ATG101 promotes cell apoptosis as well as inhibits cell autophagy and proliferation with hypoxic stimulation. Additionally, the hedgehog/Gli signal pathway is involved in ATG101-mediated macroautophagy and HPAEC proliferation. This study found that ATG101, an important member of the autophagy gene family, can regulate cell macroautophagy, apoptosis, and growth in HPAECs. ssATG101-TNP is demonstrated to be a nontoxic, highly efficient, gene-delivery vehicle for HPAECs. These findings also suggest that ATG101 might be a potential therapeutic target in diseases involving endothelial injury.

Peroxisome proliferator-activated receptor gamma (PPARγ) and miR-124 have been reported to play important roles in regulation of inflammation. However, the underlying anti-inflammatory mechanisms remain not well understood. In the present study, we demonstrated that the expression level of PPARγ is positively correlated with that of miR-124 in patients with sepsis. Activation of PPARγ upregulates miR-124 and in turn inhibits miR-124 target gene. PPARγ bound directly to PPRE in the miR-124 promoter region, and enhanced the promoter transcriptional activity. PPARγ-induced miR-124 is involved in the suppression of pro-inflammatory cytokine in vitro and in vivo. These results suggest that PPARγ-induced miR-124 inhibits the production of pro-inflammatory cytokines is a novel PPARγ anti-inflammatory mechanism and also indicate that miR-124 may be a potential therapeutic target for the treatment of inflammatory diseases.

G protein-coupled receptors (GPCRs) constitute a superfamily of cell surface receptors that regulate a variety of cell functions. As the cell surface is the functional destination for most GPCRs, the cell surface targeting process represents a crucial checkpoint in controlling the functionality of the receptors. However, the molecular mechanisms underlying the cell surface delivery of newly synthesized GPCRs remain poorly understood. In this review, we will highlight the role of Rab GTPases in GPCR cell surface transport, particularly post-Golgi traffic, and discuss the underlying molecular mechanisms.