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Traditional treatments against advanced non-small cell lung cancer (NSCLC) with high morbidity and mortality continue to be dissatisfactory. Given this situation, there is an urgent requirement for alternative modalities that provide lower invasiveness, superior clinical effectiveness, and minimal adverse effects. The combination of photodynamic therapy (PDT) and immunotherapy gradually become a promising approach for high-grade malignant NSCLC. Nevertheless, owing to the absence of precise drug delivery techniques as well as the hypoxic and immunosuppressive characteristics of the tumor microenvironment (TME), the efficacy of this combination therapy approach is less than ideal. In this study, we construct a novel nanoplatform that indocyanine green (ICG), a photosensitizer, loads into hollow manganese dioxide (MnO2) nanospheres (NPs) (ICG@MnO2), and then encapsulated in PD-L1 monoclonal antibodies (anti-PD-L1) reprogrammed exosomes (named ICG@MnO2@Exo-anti-PD-L1), to effectively modulate the TME to oppose NSCLC by the synergy of PDT and immunotherapy modalities. The ICG@MnO2@Exo-anti-PD-L1 NPs are precisely delivered to the tumor sites by targeting specially PD-L1 highly expressed cancer cells to controllably release anti-PD-L1 in the acidic TME, thereby activating T cell response. Subsequently, upon endocytic uptake by cancer cells, MnO2catalyzes the conversion of H2O2to O2, thereby alleviating tumor hypoxia. Meanwhile, ICG further utilizes O2to produce singlet oxygen (1O2) to kill tumor cells under 808 nm near-infrared (NIR) irradiation. Furthermore, a high level of intratumoral H2O2reduces MnO2to Mn2+, which remodels the immune microenvironment by polarizing macrophages from M2 to M1, further driving T cells. Taken together, the current study suggests that the ICG@MnO2@Exo-anti-PD-L1 NPs could act as a novel drug delivery platform for achieving multimodal therapy in treating NSCLC.

Tianhuang Formula (THF) is a hospital formula summarized by Professor Jiao Guo's 30 years of clinical experience. Some studies have shown that it can alleviate dyslipidemia in the body. The purpose of this study is to confirm whether THF can improve non-alcoholic fatty liver diseases (NAFLD) in type 2 diabetic mice induced by high-fat diet (HFD)/streptomycin (STZ) and to clarify its potential mechanism.

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Pancreatic cancer (PC) is the fourth leading cause of cancer death, and the 5 year survival rate is only 4%. Chemotherapy is the treatment option for the majority of PC patients diagnosed at an advanced stage, whereas the desmoplastic stroma of PC could block the perfusion of chemotherapeutic agents to tumor tissues and contribute generally to chemoresistance. Therefore, the clinical status of PC calls for an urgent exploration in the effective treatment strategy. Chemo-phototherapy is an emerging modality against malignant tumors, but owing to the low targeting ability of theranostic agents or unspecific accumulation in the tumor region, majority of chemo-phototherapy techniques have disappointing therapeutic efficiencies. Herein, we have explored CD71-specific targeting aptamers and paclitaxel (PTX)-modified polydopamine (PDA) nanospheres with the conjugation of peptidomimetic AV3 (termed Apt-PDA@PTX/AV3 bioconjugates) to specifically target and combat PC in vivo by synergistic chemo-phototherapy. After the delivery of nanotheranostic agents to the tumor microenvironment (TME) or subsequent endocytic uptake by PC cells, a simultaneous release of AV3 and PTX from Apt-PDA@PTX/AV3 bioconjugates via near-infrared (NIR) irradiation can decrease desmoplastic stroma to enhance tumor perfusion and tumor-killing effects. Meanwhile, PDA cores utilize NIR laser to create unendurable hyperthermia within TME to “cook” tumors. Taken together, the current study finally suggests that our Apt-PDA@PTX/AV3 bioconjugates could act as a novel therapeutic approach by synergistic chemo-phototherapy for the programmable inhibition of PC.

Deoxynivalenol (DON) is a prominent mycotoxin showing significant accumulation in cereal plants during infection by the phytopathogen Fusarium graminearum. It is a virulence factor that is important in the spread of F. graminearumwithin cereal heads, and it causes serious yield losses and significant contamination of cereal grains. In recent decades, genetic and genomic studies have facilitated the characterization of the molecular pathways of DON biosynthesis in F. graminearumand the environmental factors that influence DON accumulation. In addition, diverse scab resistance traits related to the repression of DON accumulation in plants have been identified, and experimental studies of wheat–pathogen interactions have contributed to understanding detoxification mechanisms in host plants. The present review illustrates and summarizes the molecular networks of DON mycotoxin production in F. graminearumand the methods of DON detoxification in plants based on the current literature, which provides molecular targets for crop improvement programs. This review also comprehensively discusses recent advances and challenges related to genetic engineering-mediated cultivar improvements to strengthen scab resistance. Furthermore, ongoing advancements in genetic engineering will enable the application of these molecular targets to develop more scab-resistant wheat cultivars with DON detoxification traits.

Global energy crisis and climate change have caused widespread concern about the development of the biomass energy industry. China has committed to exploring feasible policies to promote the development of the biomass energy industry. To analyze the impact of China’s energy tax subsidy policy (ETS) on the development of densified biomass fuel (DBF) industry, this study constructs a partial equilibrium model of the densified biomass fuel industry sector to quantitatively evaluate and optimize the effect of China’s current ETS policy based on the compilation of input–output table for the biomass energy industry sector in China. The results indicate that 1) under the current policy scenario, the price of DBF in China decreased by 15.05%, the supply increased by 40.75%, and the demand increased by 18.62%, while the price of raw biomass (RB) decreased by 14.75%, the supply increased by 42.44%, and the demand increased by 29.41%, and the revenue of enterprises increased by 20.42%. However, compared to China’s 13th Five-Year Plan national DBF development target, there is still a supply and demand gap of 16,560,549 tons. 2) under the optimized policy scenario premised on accomplishing the Chinese government’s DBF development goals, the price of DBF in China decreased by 6.9%, supply increased by 128.5%, and demand increased by 44.5%, while the price of raw biomass decreased by 7.84%, supply increased by 133.34%, demand increased by 45.71%, and corporate earnings rose by 112.1% but required the government to pay extremely high tax benefits and financial subsidies for this, which is not feasible in actual economic operation. Therefore, to support the sustainable development of the DBF industry, relevant departments should not only set the mandatory total target but also pursue production quality and market construction.

Panax notoginseng, a traditional Chinese medicine, exerts beneficial effect on diabetic kidney disease (DKD), but its mechanism is not well clarified. In this study we investigated the effects of ginsenoside Rb1 (Rb1), the main active ingredients of Panax notoginseng, in alleviating podocyte injury in diabetic nephropathy and the underlying mechanisms. In cultured mouse podocyte cells, Rb1 (10 μM) significantly inhibited high glucose-induced cell apoptosis and mitochondrial injury. Furthermore, Rb1 treatment reversed high glucose-induced increases in Cyto c, Caspase 9 and mitochondrial regulatory protein NOX4, but did not affect the upregulated expression of aldose reductase (AR). Molecular docking analysis revealed that Rb1 could combine with AR and inhibited its activity. We compared the effects of Rb1 with eparestat, a known aldose reductase inhibitor, in high glucose-treated podocytes, and found that both alleviated high glucose-induced cell apoptosis and mitochondrial damage, and Rb1 was more effective in inhibiting apoptosis. In AR-overexpressing podocytes, Rb1 (10 μM) inhibited AR-mediated ROS overproduction and protected against high glucose-induced mitochondrial injury. In streptozotocin-induced DKD mice, administration of Rb1 (40 mg·kg−1·d−1, ig, for 7 weeks) significantly mitigated diabetic-induced glomerular injuries, such as glomerular hypertrophy and mesangial matrix expansion, and reduced the expression of apoptotic proteins. Collectively, Rb1 combines with AR to alleviate high glucose-induced podocyte apoptosis and mitochondrial damage, and effectively mitigates the progression of diabetic kidney disease.

The artificial enzymes at the atomic level have shown great potential in chemical biology and nanomedicine, and modulation of catalytic selectivity is also critical to the application of nanozymes. In this work, atomic precision Ag25clusterzymes protected by single- and dual-ligand were developed. Further, the catalytic activity and selectivity of Ag25clusterzymes were modulated by adjusting doping elements and ligand. The Ag24Pt1shows more prominent antioxidant activity characteristics in the dual-ligand system, while the Ag24Cu1possesses the superoxide dismutase-like (SOD-like) activity regardless of the single- or dual-ligand system, indicating modulated catalytic selectivity. In vitroexperiments showed the Ag24Pt1-D can recover radiation induced DNA damages and eliminate the excessive reactive oxygen species (ROS) generated from radiation. Subsequent in vivoradiation protection experiments reveal that Ag24Cu1-S and Ag24Pt1-D can improve the survival rate of irradiated mice from 0 to 40% and 30%, respectively. The detailed biological experiments confirm that the Ag24Cu1-S and Ag24Pt1-D can recover the SOD and 3,4-methylenedioxyamphetamine (MDA) levels via suppressing the chronic inflammation reaction. Nearly 60% of Ag24Cu1-S and Ag24Pt1-D can be excreted after a 1 day injection, and no obvious toxicological reactions were observed 30 days after injection.

A dual‐view 3‐D display with multiple resolutions is proposed. The proposed 3‐D display consists of a 2‐D display panel and a parallax barrier. The parallax barrier can project the parallax image on the 2‐D display panel into views and form several viewing zones. By making viewing zones overlapping, the proposed 3‐D display can improve the resolution of the image in the overlapped area and provide multiple resolutions. Finally, the resolution is improved at the center area of a viewing zone, where there is high‐probability viewing position of the observers. A prototype is developed to verify the principle. The experimental results show that the proposed 3‐D display can improve resolution. Viewing zones overlapping is applied to improve resolution of dual‐view 3‐D display and provide multiple resolutions. The viewing zones overlapping is achieved by projecting viewing zones with different width to the same position. A prototype with two kinds of resolution is also fabricated.

For this study, a Sb2WO6/Bi4O5I2composite material was successfully prepared via a precipitation-calcination method. The Sb2WO6/Bi4O5I2heterostructure enhanced the light absorption and facilitated the separation of charge carriers. Under simulated sunlight exposure, the removal rates of tetracycline (TC) and doxycycline hyclate (DOX·HCl) reached 88.2% and 83.9%, respectively, over an optimized SWB2 composite (theoretical mole ratio of Sb2WO6: BiOI was 1.5:10). Further, the total organic carbon (TOC) removal rates were 37.6% and 33.7%, respectively. The experiments explored various parameters including catalyst dosage, initial concentrations of TC and DOX·HCl, solution pH, and common inorganic ions. The TC and DOX·HCl degradation pathways were speculated. Furthermore, SWB2 demonstrated remarkable stability and cyclability under simulated sunlight. Trapping experiments and electron paramagnetic resonance (EPR) tests revealed that •O2-played a major role as a free radical in the photocatalytic process, while h+and •OH also had significant contributions. Based on in-situ XPS, trapping experiments, EPR test, band bending analysis, and SPV tests, the formation of S-scheme heterojunction between Sb2WO6and Bi4O5I2was inferred. This study provides insights into the design strategy of S-scheme heterojunctions between Aurivillius-type compounds and bismuth-rich halide bismuth oxide, which is informative for the development of advanced environmental remediation concepts.

Mosquito-borne Japanese encephalitis virus (JEV) causes serious illness worldwide and is associated with high morbidity and mortality. To identify potential host therapeutic targets, a high-throughput receptor tyrosine kinase small interfering RNA library screening was performed with recombinant JEV particles.

Diabetes and its related metabolic disorders have been reported as the leading comorbidities in patients with coronavirus disease 2019 (COVID-19). This clinical study aims to investigate the clinical features, radiographic and laboratory tests, complications, treatments, and clinical outcomes in COVID-19 patients with or without diabetes. This retrospective study included 208 hospitalized patients (≥ 45 years old) with laboratory-confirmed COVID-19 during the period between 12 January and 25 March 2020. Information from the medical record, including clinical features, radiographic and laboratory tests, complications, treatments, and clinical outcomes, were extracted for the analysis. 96 (46.2%) patients had comorbidity with type 2 diabetes. In COVID-19 patients with type 2 diabetes, the coexistence of hypertension (58.3% vs 31.2%), coronary heart disease (17.1% vs 8.0%), and chronic kidney diseases (6.2% vs 0%) was significantly higher than in COVID-19 patients without type 2 diabetes. The frequency and degree of abnormalities in computed tomography (CT) chest scans in COVID-19 patients with type 2 diabetes were markedly increased, including ground-glass opacity (85.6% vs 64.9%, P < 0.001) and bilateral patchy shadowing (76.7% vs 37.8%, P < 0.001). In addition, the levels of blood glucose (7.23 mmol·L−1(interquartile range (IQR): 5.80–9.29) vs 5.46 mmol·L−1(IQR: 5.00–6.46)), blood low-density lipoprotein cholesterol (LDL-C) (2.21 mmol·L−1(IQR: 1.67–2.76) vs 1.75 mmol·L−1(IQR: 1.27–2.01)), and systolic pressure (130 mmHg (IQR: 120–142) vs 122 mmHg (IQR: 110–137)) (1 mmHg = 133.3 Pa) in COVID-19 patients with diabetes were significantly higher than in patients without diabetes (P < 0.001). The coexistence of type 2 diabetes and other metabolic disorders is common in patients with COVID-19, which may potentiate the morbidity and aggravate COVID-19 progression. Optimal management of the metabolic hemostasis of glucose and lipids is the key to ensuring better clinical outcomes. Increased clinical vigilance is warranted for COVID-19 patients with diabetes and other metabolic diseases that are fundamental and chronic conditions.

In this paper, we proposed a light field resampling method for generating elemental image array (EIA) of integral imaging. The proposed method can break through the constraints between parameters of traditional integral imaging record device and display device and allow to generate a new set of EIA suited to be displayed in an integral imaging display device with arbitrary parameters from any given recorded EIA. Three‐dimensional display results show the correctness and superiority of the proposed method. In this paper, we proposed a light field resampling method for generating elemental image array of integral imaging. It consists of two steps that are 3D coordinates restoration and light field resampling. The proposed method can generate a new set of EIA suited to be displayed in an integral imaging display device with arbitrary parameters from any given recorded EIA.

Obesity has an important influence on health conditions, causing a multitude of complications and comorbidities, and drug therapy is considered to be one of the treatment strategies. Nowadays, there is increasing interest in the study of intestinal microbiota regulation of obesity; also, an increasing number of agricultural and sideline products have been found to have anti-obesity potential. In the present review, we summarize an overview of current known and potential anti-obesity oligosaccharides and their molecular structures. We describe their anti-obesity potential activity and the molecular structure associated with this activity, the regulation of intestinal microbiota composition and its mechanism of action, including regulation of the short-chain fatty acid (SCFA) pathway and altering bile acid (BA) pathway. This review will provide new ideas for us to develop new anti-obesity functional foods.

Supplemental Digital Content is available in the text.

Lassa virus (LASV) is an enveloped, negative-sense RNA virus that causes Lassa hemorrhagic fever. Successful entry of LASV requires the viral glycoprotein 1 (GP1) to undergo a receptor switch from its primary receptor alpha-dystroglycan (α-DG) to its endosomal receptor lysosome-associated membrane protein 1 (LAMP1). A conserved histidine triad in LASV GP1 has been reported to be responsible for receptor switch. To test the hypothesis that other non-conserved residues also contribute to receptor switch, we constructed a series of mutant LASV GP1 proteins and tested them for binding to LAMP1. Four residues, L84, K88, L107, and H170, were identified as critical for receptor switch. Substituting any of the four residues with the corresponding lymphocytic choriomeningitis virus (LCMV) residue (L84N, K88E, L10F, and H170S) reduced the binding affinity of LASV GP1 for LAMP1. Moreover, all mutations caused decreases in glycoprotein precursor (GPC)-mediated membrane fusion at both pH 4.5 and 5.2. The infectivity of pseudotyped viruses bearing either GPCL84Nor GPCK88Edecreased sharply in multiple cell types, while L107F and H170S had only mild effects on infectivity. Using biolayer light interferometry assay, we found that all four mutants had decreased binding affinity to LAMP1, in the order of binding affinity is L84N > L107F > K88E > H170S. The four amino acid loci identified for the first time in this study have important reference significance for the in-depth investigation of the mechanism of receptor switching and immune escape of LASV occurrence and the development of reserve anti-LASV infection drugs.

ABSTRACTGestational diabetes mellitus (GDM) is characterized by the development of hyperglycemia and insulin resistance during the second or third trimester of pregnancy, associated with considerable risks to both the mother and developing fetus. Although emerging evidence suggests an association between the altered gut microbiota and GDM, remarkably little is known about the microbial and metabolic mechanisms that link the dysbiosis of the gut microbiota to the development of GDM. In this study, a metagenome-wide association study and serum metabolomics profiling were performed in a cohort of pregnant women with GDM and pregnant women with normal glucose tolerance (NGT). We identified gut microbial alterations associated with GDM and linked to the changes in circulating metabolites. Blood metabolite profiles revealed that GDM patients exhibited a marked increase in 2-hydroxybutyric acid and L-alpha-aminobutyric acid, but a decrease in methionine sulfoxide, allantoin, and dopamine and dopaminergic synapse, when compared with those in NGT controls. Short-chain fatty acid-producing genera, including Faecalibacterium, Prevotella, and Streptococcus, and species Bacteroides coprophilus, Eubacterium siraeum, Faecalibacterium prausnitzii, Prevotella copri, and Prevotella stercorea, were significantly reduced in GDM patients relative to those in NGT controls. Bacterial co-occurrence network analysis revealed that pro-inflammatory bacteria were over-represented as the core species in GDM patients. These microbial and metabolic signatures are closely associated with clinical parameters of glucose metabolism in GDM patients and NGT controls. In conclusion, we identified circulating dopamine insufficiency, imbalanced production of SCFAs, and excessive metabolic inflammation as gut microbiota-driven multiple parallel hits linked to GDM development. This work might explain in part the mechanistic link between altered gut microbiota and GDM pathogenesis, and suggest that gut microbiota may serve as a promising target to intervene in GDM.

Carbonylation with CO surrogates is one of the most common methods for introduction of carbonyl groups in ketone synthesis. However, arylhydrazides have not been used as an aryl source in this denitrogenative method even though they are cheap and accessible. Here, we report development of palladium catalysis for the three‐component reactions of arylboronic acids, CO‐surrogates (benzene‐1,3,5‐triyl triformate), and arylhydrazides under oxygen conditions to produce diaryl ketones. (Hetero)arylhydrazides, as well as (hetero)arylboronic acids are suitable reaction partners, and good functional group compatibility was achieved. This method could be used for streamlined synthesis of diaryl ketones, ketoprofen and fenofibrate. A Pd‐catalyzed oxidative carbonylation of arylhydrazines and phenylboronic acids which provides access to diaryl ketones with N2and H2O as the only byproducts is reported.

Macrophages play an important role in a wide variety of physiologic and pathologic processes. Plasticity and functional polarization are hallmarks of macrophages. Macrophages commonly exist in two distinct subsets: classically activated macrophages (M1) and alternatively activated macrophages (M2). M2b, a subtype of M2 macrophages, has attracted increasing attention over the past decade due to its strong immune‐regulated and anti‐inflammatory effects. A wide variety of stimuli and multiple factors modulate M2b macrophage polarization in vitro and in vivo. M2b macrophages possess both protective and pathogenic roles in various diseases. Understanding the mechanisms of M2b macrophage activation and the modulation of their polarization might provide a great perspective for the design of novel therapeutic strategies. The purpose of this review is to discuss current knowledge of M2b macrophage polarization, the roles of M2b macrophages in a variety of diseases and the stimuli to modulate M2b macrophage polarization. Review outlines the current knowledge of the stimuli of M2b macrophage polarization and the roles of these cells in diseases.

Industrial robots are widely used in various applications such as machining, painting, and welding. There is a pressing need for a fast and straightforward robot programming method, especially for surface-based tasks. At present, these tasks are time-consuming and expensive, and it requires an experienced and skilled operator to program the robot for a specific task. Hence, it is essential to automate the tool-path generation in order to eliminate the manual planning. This challenging research has attracted great attention from both industry and academia. In this paper, a tool-path generation method based on a mesh model is introduced. The bounding box tree and kd-tree are adopted in the algorithm to derive the tool path. In addition, the algorithm is integrated into an offline robot programming system offering a comprehensive solution for robot modeling, simulation, as well as tool-path generation. Finally, a milling experiment is performed by creating tool paths on the surface thereby demonstrating the effectiveness of the system.

We propose a dual-view integral imaging display using a polarizer. It consists of a display panel, a polarizer, a microlens array, and two pairs of polarizer glasses. The polarizer comprises the left and right subpolarizers whose polarization directions are orthogonal. Two kinds of elemental images are captured from different three-dimensional scenes and located on the left and right half of the display panel. The lights emitting from two kinds of elemental images are polarized by the left and right subpolarizers. The polarization directions of the two pairs of polarizer glasses used in the left and right viewing zones are the same as those of the right and left subpolarizers, respectively. Two different three-dimensional images are simultaneously viewed in the left and right viewing directions by wearing two pairs of polarizer glasses. A prototype of the proposed dual-view integral imaging display is developed, and the experimental results verify the hypothesis.

In this contribution, an efficient and green protocol for alcoholysis of waste polycarbonate (PC) using Lewis acidic ionic liquids (ILs) was first developed under mild and solvent-free conditions. The influence of Lewis acidity and reaction parameters on the catalytic activity were thoroughly studied. It showed that with only 5.0 mol % [Bmim]Cl·2.0FeCl3loading, 100% PC conversion with 97.2% bisphenol A (BPA) yield was efficiently obtained at 120 °C and n(CH3OH)/n(PC) = 6:1 for 3.0 h. The alcohol scopes for depolymerization of waste PC into BPA monomer were examined, and the moderate to excellent product yields were obtained under the optimized conditions. Also the [Bmim]Cl·2.0FeCl3catalyst could be reused five successive times without a significant decrease of the catalytic activity. Combining the kinetic study and the in situ FT-IR analysis, a feasible reaction mechanism was proposed.

An autostereoscopic 3D display with high brightness and low crosstalk is proposed. This display consists of a liquid crystal display (LCD) panel, a reflective light source (RLS), and a parallax barrier or lenticular lens. The RLS behind the LCD panel consists of a light source, a light guide plate, and a reflection cavity. The RLS can make light reflect continuously in the reflection cavity and exit from the slits on the cavity surface. The widths of these slits are narrower than those of the subpixels, so they can provide a low aperture ratio, which is helpful in obtaining low crosstalk. Because of the reflection cavity, the optical efficiency is higher than that using a single barrier. The parallax barrier or lenticular lens can project parallax images on the LCD panel into different directions. Then 3D images are formed. A prototype of the proposed 3D display having high brightness 3D images and low crosstalk is developed. The experimental results agree well with the theory.

Five coordination polymers, [Co(H3L)2(dib)]·1.5H2O(1), [Cu(H3L)2(dib)](2), [Co(H3L)(mtpy)]·DMF(3), [Ni(H3L)2(mtpy)(H2O)]·3DMF·H2O(4), and [Cd(H3L)2(pybim)]·1.5H2O(5), have been successfully prepared from 5,11,17,23-tetra-tert-butyl-25-(carboxymethoxy)calix[4]arene, metal salts, and N-donor auxiliary ligands under hydrothermal conditions[dib=1,4-di(1H-imidazol-1-yl)butane, pybim=2-(2'-pyridyl)benzimidazole, and mtpy=4'-(4- methylphenyl)-2,2':6',2''-terpyridine]. Structural analysis suggests that the metal ion first joins two organic carboxy-late ligands to form the independent units, which are further extended by the N-donor auxiliary ligand to give the final structure. Compounds 1and 2display 1D infinite chains bridged by a flexible bidentate dib ligand. Compounds 3―5, with multidentate chelate ligands, reveal discrete 0D units. Furthermore, in compounds 3and 5, 1D supramolecular architectures are exhibited due to π-πinteractions.