The recent human infection with avian influenza virus revealed that H9N2 influenza virus is the gene donor for H7N9 and H10N8 viruses infecting humans. The crucial role of H9N2 viruses at the ...animal-human interface might be due to the wide host range, adaptation in both poultry and mammalian, and extensive gene reassortment. As the most prevalent subtype of influenza viruses in chickens in China, H9N2 also causes a great economic loss for the poultry industry, even under the long-term vaccination programs. The history, epidemiology, bio- logical characteristics, and molecular determinants of H9N2 influenza virus are reviewed in this paper. The contribution of H9N2 genes, especially RNP genes, to the infection of humans needs to be investigated in the future.
Programmed death protein 1 (PD1) is a common immunosuppressive member on the surface of T cells and plays an imperative part in downregulating the immune system and advancing self-tolerance. Its ...ligand programmed cell death ligand 1 (PDL1) is overexpressed on the surface of malignant tumor cells, where it binds to PD1, inhibits the proliferation of PD1-positive cells, and participates in the immune evasion of tumors leading to treatment failure. The PD1/PDL1-based pathway is of great value in immunotherapy of cancer and has become an important immune checkpoint in recent years, so understanding the mechanism of PD1/PDL1 action is of great significance for combined immunotherapy and patient prognosis. The inhibitors of PD1/PDL1 have shown clinical efficacy in many tumors, for example, blockade of PD1 or PDL1 with specific antibodies enhances T cell responses and mediates antitumor activity. However, some patients are prone to develop drug resistance, resulting in poor treatment outcomes, which is rooted in the insensitivity of patients to targeted inhibitors. In this paper, we reviewed the mechanism and application of PD1/PDL1 checkpoint inhibitors in tumor immunotherapy. We hope that in the future, promising combination therapy regimens can be developed to allow immunotherapeutic tools to play an important role in tumor treatment. We also discuss the safety issues of immunotherapy and further reflect on the effectiveness of the treatment and the side effects it brings.
It is of great practical significance to explore the green development path of regional economy and environment. In this paper, Yangtze River Economic Belt in China was selected as the research ...objects, entropy method and coupling coordination degree model were used to calculate and analyse the ecological and economic changes and coordination degree. The results show that the condition of ecology and economy of the Yangtze River Economic Belt are on the rise, and the overall economy is developing rapidly. Although the economy of some regions is on the rise, it is still relatively backward. The ecological situation has been improved, the improvement range is small, and there are regional differences. Overall, the coordination degree of ecological economy has improved, but there are also spatial differences. In order to promote the coordinated development of ecological economy in the Yangtze River Economic Belt, it is suggested to strengthen the treatment of ecological environment pollution, build a modern economic system and promote green development.
Protein/antibody therapeutics have exhibited the advantages of high specificity and activity even at an extremely low concentration compared to small molecule drugs. However, they are accompanied by ...unfavorable physicochemical properties such as fragile tertiary structure, large molecular size, and poor penetration of the membrane, and thus the clinical use of protein drugs is hindered by inefficient delivery of proteins into the host cells. To overcome the challenges associated with protein therapeutics and enhance their biopharmaceutical applications, various protein‐loaded nanocarriers with desired functions, such as lipid nanocapsules, polymeric nanoparticles, inorganic nanoparticles, and peptides, are developed. In this review, the different strategies for intracellular delivery of proteins are comprehensively summarized. Their designed routes, mechanisms of action, and potential therapeutics in live cells or in vivo are discussed in detail. Furthermore, the perspective on the new generation of delivery systems toward the emerging area of protein‐based therapeutics is presented as well.
Intracellular protein delivery is a powerful tool for a wide array of therapeutic purposes. Various nanoparticle‐based systems for intracellular delivery of proteins are comprehensively summarized. Their designed routes, action mechanisms, and potential therapeutics are discussed in detail. Furthermore, the perspective of new generation delivery systems toward the emerging area of protein‐based therapeutics is presented.
Coalbed methane (CBM) drilling and completion technologies (DCTs) are significant basis for achieving efficient CBM exploration and exploitation. Characteristics of CBM reservoirs vary in different ...regions around the world, thereby, it is crucial to develop, select and apply the optimum DCTs for each different CBM reservoir. This paper firstly reviews the development history of CBM DCTs throughout worldwide and clarifies its overall development tendency. Secondly, different well types and its characteristics of CBM exploitation are summarized, and main application scopes of these well types are also discussed. Then, the key technologies of CBM drilling (directional drilling tools, measurement while drilling, geo-steering drilling, magnetic guidance drilling, underbalanced drilling and drilling fluids), and the key technologies of CBM completion (open-hole, cavity and under-ream completion, cased-hole completion, screen pipe completion and horizontal well completion) are summarized and analyzed, it is found that safe, economic and efficient development of CBM is inseparable from the support of advanced technologies. Finally, based on the current status of CBM development, the achievements, existing challenges and future prospects are summarized and discussed from the perspective of CBM DCTs.
Mapping and dating the fresh moraines close to the termini of glaciers have significantly improved the understanding of glacier changes in the past millennium. However, it is challenging to ...reconstruct the continuous change of glaciers due to the fragmentary nature of the moraine record. We combine glacial modeling with geomorphological mapping and 10Be surface exposure dating of moraine boulders to reconstruct the fluctuations of two valley glaciers (Qiangyong Glacier and Karola West Valley Glacier) in the Mt. Noijin Kangsang area, southern Tibetan Plateau, during the Little Ice Age (LIA). We first constrain the formation age of the fresh moraine close to Qiangyong Glacier using 10Be surface exposure dating and re-analyze the six previously published 10Be exposure ages in front of the Karola West Valley Glacier. Then, the Open Global Glacier Model (OGGM) is used to simulate the continuous changes of the glaciers from 900 to 2000 CE based on the climate records of 8 General Circulation Models (GCMs). The simulated results are verified with mapped lengths and extents of the glaciers and reconstructed ice volumes using an ArcGIS-based flowline model, PalaeoIce. Four 10Be surface exposure ages indicate that the moraine close to Qiangyong Glacier was formed at 333 ± 44 a, corresponding to the LIA. The OGGM simulations show four major glacial advances of the two glaciers around 1281 CE, 1473 CE, 1666 CE, and 1837 CE, corresponding to four temperature depressions. The lengths, areas, and volumes of these two glaciers have retreated by 20.5%, 14.7%, and 36.5%, respectively, since the LIA. The OGGM-simulated glacier length and area changes are similar to the mapped results (< 3% differences). Adding to the uncertainties in the ice thickness estimate, the differences between the ice volumes reconstructed by OGGM and PalaeoIce are 6% and 12% for the LIA glaciers in the Karola West Valley and Qiangyong Valley, respectively. This study provides important insights into the response of glaciers to climate change over the past millennium on the southern Tibetan Plateau.
•We simulated the continuous changes of two glaciers on southern Tibet during the LIA.•The moraine close to Qiangyong Glacier was dated to LIA by 10Be exposure ages.•OGGM simulations reveal four LIA sub-stages around 1309, 1488, 1697, and 1866 CE.•OGGM-simulated changes of the two glaciers are similar to their mapped changes.
Controlling and managing surface source pollution depends on the rapid monitoring of total nitrogen in water. However, the complex factors affecting water quality (plant shading and suspended matter ...in water) make direct estimation extremely challenging. Considering the spectral response mechanisms of emergent plants, we coupled discrete wavelet transform (DWT) and fractional order discretization (FOD) techniques with three machine learning models (random forest (RF), bagging algorithm (bagging), and eXtreme Gradient Boosting (XGBoost)) to mine this potential spectral information. A total of 567 models were developed, and airborne hyperspectral data processed with various DWT scales and FOD techniques were compared. The effective information in the hyperspectral reflectance data were better emphasized after DWT processing. After DWT processing the original spectrum (OR), its sensitivity to TN in water was maximally improved by 0.22, and the correlation between FOD and TN in water was optimally increased by 0.57. The transformed spectral information enhanced the TN model accuracy, especially for FOD after DWT. For RF, 82% of the model R2 values improved by 0.02~0.72 compared to the model using FOD spectra; 78.8% of the bagging values improved by 0.01~0.53 and 65.0% of the XGBoost values improved by 0.01~0.64. The XGBoost model with DWT coupled with grey relation analysis (GRA) yielded the best estimation accuracy, with the highest precision of R2 = 0.91 for L6. In conclusion, appropriately scaled DWT analysis can substantially improve the accuracy of extracting TN from UAV hyperspectral images. These outcomes may facilitate the further development of accurate water quality monitoring in sophisticated global waters from drone or satellite hyperspectral data.
Mitocbondrial fusion is a highly coordinated process that mixes and unifies the mitochondrial compartment for normal mitochondrial functions and mitochondrial DNA inheritance. Dysregulated ...mitochondrial fusion causes mitochondrial fragmentation, abnormal mitochondrial physiology and inheritance, and has been causally linked with a number of neuronal diseases. Here, we identified a diterpenoid derivative 15-oxospiramilactone （$3） that potently induced mitochondrial fusion to restore the mitochondrial network and oxidative respiration in cells that are deficient in either Mfnl or Mfn2. A mitochondria-localized deubiquitinase USP30 is a target of $3. The inhibition of USP30 by $3 leads to an increase of non-degradative ubiquitination of Mfnl/2, which enhances Mfnl and Mfn2 activity and promotes mitochondrial fusion. Thus, through the use of an inhibitor of USP30, our study uncovers an unconventional function of non-degradative ubiquitination of Mfns in promoting mitochondrial fusion.
The formation of amide bonds is one of the most valuable transformations in organic synthesis. Beckmann rearrangement is a well-known method for producing secondary amides from ketoximes. This study ...demonstrates the rapid synthesis of ketoximes and amides in microdroplets. Many factors are found to affect the yield, such as microdroplet generation devices, temperature, catalysts, and concentrations of reactants. In particular, the temperature has a great influence on the synthesis of amide, which is demonstrated by a sharp ascendance to the yield when the temperature was increased to 45 °C. The best amide yield (93.3%) can be obtained by using coaxial flowing devices, a sulfonyl chloride compound as a catalyst, and heating to 55 °C in microdroplets. The yields can reach 78.7–91.3% for benzoylaniline and 87.2–93.4% for benzophenone oximes in several seconds in microdroplets compared to 10.1–66.1% and 82.5–93.3% in several hours in the bulk phase. Apart from the dramatically decreased reaction time and enhanced reaction yields, the microdroplet synthesis is also free of severe reaction environments (anhydrous and anaerobic conditions). In addition, the synthesis in microdroplets also saves reactants and solvents and reduces the waste amounts. All of these merits indicate that the microdroplet synthesis is a high-efficiency green methodology.
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