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Global warming intensifies atmospheric water vapor transport between ocean and land, which increases the likelihood of extreme precipitation and floods. However, accurate estimations of water vapor exchange between ocean and land are difficult due to the lack of available data and effective methods. This study developed a novel eightdirection- vector decomposition algorithm for calculating water vapor flux between ocean and land based on the ERA5 reanalysis dataset, and the results showed that global water vapor exchange between ocean and land had significantly increased in the past 40 years, except for Antarctica. During 1980-2018, the average annual net water vapor inflow from ocean to land (Qnet) was 44.68×1015 kg/yr, and Qnet increased at a rate of 1.48×1015 kg/yr per decade. The intensified atmospheric water vapor exchange between ocean and land was directly caused by the increase of atmospheric water vapor content, which largely depended on the rising air temperature, and it was found that water vapor flux between ocean and land increased by over 8%/K with the increasing air temperature at the global average. This study also identified El Niño-Southern Oscillation (ENSO) as an important contributor to the global ocean-land water vapor exchange anomalies. A strong El Niño event (MEI=1) can result in a 1.36×1015 kg/yr (3.03%) decrease in Qnet , and a strong La Nina event (MEI=-1) can increase Qnet by 1.38×1015 kg/yr (3.09%). The eight-direction-vector decomposition algorithm was effective in ocean-land water vapor flux estimations at different spatial and temporal scales, which could provide great insights into the mechanisms of extreme precipitation events.

At present, the traditional phase unwrapping algorithm is difficult to balance the accuracy and unwrapping efficiency. The traditional phase unwrapping algorithm is difficult to balance the accuracy and efficiency in the phase unwrapping experiments of simulated and measured topographic interferograms. In this paper, the phase unwrapping technology will be studied under the framework of deep learning theory according to the development trend of InSAR intelligence. A phase unwrapping algorithm based on deep GAN is proposed. The model structure includes dense convolution layer blocks and series structure, so that the network can achieve a better balance between feature extraction and detail preservation of interferogram. This is helpful to improve the phase unwrapping accuracy and training efficiency of the network. The experimental results show that the algorithm has a good expansion effect on the interferogram with high signal-to-noise ratio. The synthesis algorithm makes full use of the advantages of the branch cutting method and the finite element method. The phase reliable region and unreliable region are determined, and the transmission of phase error from the unreliable region to reliable region is effectively avoided. The accuracy of the phase unwrapping results in the reliable region is ensured, and the overall phase unwrapping convergence accuracy is greatly improved.

Conventional hepatic artery and portal vein clamping strategies can prevent blood loss and ischemia-reperfusion liver injury, and such preventative measures are the key to successful liver surgery. However, ischemic-induced damage to cholangiocytes is rarely considered. Here, we aimed to investigate the effect of different hepatic inflow interruption methods on bile duct injury. Forty rats were randomly grouped as sham, Pringle maneuver (PM) and hepatic arterial blood flow open (HAFO) groups. We evaluated liver histology and function in liver sections, and biliary histology, cholangiocyte apoptosis and proliferation, cytokine production, and bile composition. RNA sequencing is performed to explore possible molecular mechanisms. The Blood-biliary barrier permeability and tight junctions were analyzed by HRP injection, immunofluorescence staining and analysis of ZO-1 expression by immunoblotting. HAFO significantly attenuated ischemia-induced liver injury and decreased ALT, ALP, TBIL, and DBIL levels in serum. The histopathological observations showed that bile duct injury in the PM group was more serious than that in the HAFO group. The numbers of apoptotic biliary epithelial cells in HAFO-treated rat bile ducta were lower than those in the PM group. RNA-seq showed that tight junctions may be related to the mechanism underlying the protective effect of HAFO, as shown by the reduced HRP levels and increased ZO-1 and claudin-1/3 expression in the HAFO group compared to the PM group. Compared with PM, HAFO alleviated the ischemic injury to the biliary system, which was characterized by decreased biliary epithelial cell apoptosis, reduced inflammatory responses and decreased blood-biliary-barrier permeability.

The effects of addition of minor amount of (0.5 wt.%) antimony (Sb) or gadolinium (Gd) and combined addition of Sb and Gd (0.5 wt.%, respectively) on the hot tearing susceptibility (HTS) of Mg-5Al-3Ca alloy were investigated experimentally using a “T-shaped” hot tearing measuring system. Various solidification parameters of the alloys were measured and calculated through thermal analysis experiments. The microstructure, grain size, and morphology of the crack zone were characterized by scanning electron microscopy and electron backscatter diffraction, and the crystal phases of the alloys were analyzed by X-ray diffraction and energy-dispersive X-ray spectroscopy. The results showed that the addition of 0.5 wt.% Gd resulted in the increase in the vulnerable temperature range (Tv) and reduced the eutectic structure content that could participate in feeding, thereby improving the HTS of the alloy. However, addition of 0.5 wt.% Sb or combined addition of Gd and Sb (0.5 wt.%, respectively) to the Mg-5Al-3Ca alloy shortened the Tv and improved the skeleton strength of the alloy, thereby reducing HTS. Moreover, significantly refined structure of Mg-5Al-3Ca-0.5Gd-0.5Sb alloy improved the feeding ability of the eutectic structure, thus the alloy exhibited the lowest HTS.

As a typical feature of a reservoir, heterogeneity is the main reason for low oil recovery and the poor effect of acidizing measures. Diversion is the main measure to improve the acidizing effect. Over the years, technological progress has mainly focused on the material development of diverting agents. In this study, the diverting effect and influencing factors for a viscous fluid were systematically studied by the heterogeneous dual-core flooding experiment. The results are as follows: First, increasing the displacement pressure in heterogeneous reservoirs can improve the diverting effect, which is consistent with maximum differential pressure and injection rate (MADPIR) theory, but the diverting effect is weak. The injection pressure difference is increased by 50 times, and the diverting effect is improved by 16.27% at most. Second, taking a viscous fluid as the stimulation fluid can partially realize the diversion for heterogeneous reservoir and further improve the acidizing effect, and the breaking through PV can be improved by 78% at most. Using a viscous fluid as a diverting agent can achieve 100% balanced acid injection. Third, compared with a viscoelastic surfactant, a relatively uniform and stable polymer solution as the diverting agent has the possibility to completely block the low-permeability layer. So, a 5% viscoelastic surfactant as the diverting agent is more suitable for acidizing. Finally, any diverter injected into the formation will enter all layers. The conclusion that the diverting agent only enters the high-permeability layer but not the low-permeability layer is not tenable. Diverting acidizing is only effective for near-well zones, which is difficult to fundamentally solve the seepage problem of heterogeneous reservoirs.

Cholesterol overloading stress damages normal cellular functions in hepatocytes and induces metabolic disorders to facilitate the development of multiple diseases, including cardiovascular diseases, which seriously degrades the life quality of human beings. Recent data suggest that the Berberis vulgaris L. extract berberine is capable of regulating cholesterol homeostasis, which is deemed as potential therapeutic drug for the treatment of cholesterol overloading-associated diseases, but its detailed functions and molecular mechanisms are still largely unknown. In the present study, we evidenced that berberine suppressed cell apoptosis in high-cholesterol-diet mice liver and cholesterol-overloaded mice hepatocytes. Also, cholesterol overloading promoted reactive oxygen species (ROS) generation to trigger oxidative damages in hepatocytes, which were reversed by co-treating cells with both berberine and the ROS scavenger N-acetylcysteine (NAC). Moreover, the underlying mechanisms were uncovered, and we validated that berberine downregulated Keap1, and upregulated Nrf2 to activate the anti-oxidant Nrf2/HO-1 signaling pathway in cholesterol overloading-treated hepatocytes, and both Keap1 upregulation and Nrf2 downregulation abrogated the suppressing effects of berberine on cell apoptosis in the hepatocytes with cholesterol exposure. Taken together, we concluded that berberine activated the anti-oxidant Keap1/Nrf2/HO-1 pathway to eliminate cholesterol overloading-induced oxidative stress and apoptotic cell death in mice hepatocytes, and those evidences hinted that berberine might be used as putative therapeutic drug for the treatment of cholesterol overloading-associated cardiovascular diseases.

Previous studies have demonstrated that both CS and LiCl possess anti-Alzheimer’s disease (AD) activities. We prepared chondroitin sulfate-Li (CS-Li) and investigated its effect on AD and explored the possible mechanisms both in vitro and in vivo. We found that CS-Li could inhibit amyloid β (Aβ) aggregation and protect SH-SY5Y cells from Aβ1-42-induced cytotoxicity in vitro. In D-gal and AlCl3-induced AD mouse model, CS-Li improves the spatial learning and memory abilities of AD mice, reverses the nuclear pyknosis and cell edema, and increases the survival rate of neurons in hippocampus of mice. Moreover, CS-Li significantly increased the levels of GSH-Px, Na+/K+-ATPase, and ChAT and decreased the levels of MDA and AchE in AD mice. Western blot results demonstrated that CS-Li could decrease the hyperphosphorylation of tau (Ser396/Ser404) by regulating the expression of p-GSK-3β (Ser9) and PP2A and inhibit the expression of proinflammatory factors through inhibiting NF-κB nuclear translocation by activating the MAPK signaling pathways. In a word, CS-Li can delay AD development through multitarget processes, including Aβ aggregation inhibition, oxidative stress damage, tau hyperphosphorylation, and inflammatory response, thereby improves learning and memory abilities.

Immune checkpoint inhibitors (ICIs) have successfully treated a number of different types of cancer, which is of great significance for cancer treatment. With the widespread use of ICIs in clinical practice, the increasing checkpoint inhibitor pneumonia (CIP) will be a challenge to clinicians. To guide the diagnosis and treatment of CIP, we conducted in-depth discussions based on the latest evidence, forming a consensus among Chinese experts on the multidisciplinary management of CIP.

This paper investigates the problem of fixed-time attitude coordinated control for multi-spacecraft systems with unknown external disturbance. Firstly, a distributed fixed-time observer is introduced to estimate the states of the virtual leader. The observer can track the leader completely in a fixed time without dependence on the initial conditions of the leader and observer. Then, we propose a novel nonsingular fixed-time sliding mode tracking controller to address the fixed-time attitude tracking problem. It is noteworthy that the requirement on initial conditions of spacecraft is removed in the proposed nonsingular sliding mode controller. Due to the robustness of sliding mode control, the influence of external disturbance can be eliminated, such that each spacecraft can track desired attitude trajectories precisely in a fixed time. Hence, the fixed-time attitude coordination for multiple spacecraft can be achieved. Finally, numerical simulation results and comparisons reveal the effectiveness of the proposed algorithms.

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.

Cell-free compounds of mesenchymal stem cells (MSCs) could be a safer and cheaper substitution for MSC transplantation and have gained substantial research interest for antiaging skin treatments. However, whether those bioactive components should be obtained from the cytoplasm or supernatant is yet to be determined. In this study, we examined the ingredients of the MSC cytoplasm extract (MSC-ex) and MSC supernatant (MSC-s) and evaluated their effect in a photoaging model. Although MSC-ex has a richer protein composition than MSC-s, the latter has a proteome associated with wound healing and blood vessel development. Over 85% of the proteins in MSC-s were also found in MSC-ex, including extracellular matrix protein and various growth factors. The results of real-time PCR and western blot also demonstrate that both MSC-s and MSC-ex can upregulate collagen, transforming growth factor β (TGF-β), and vascular endothelial growth factor (VEGF) and downregulate IL-1β and matrix metalloproteinase-1 (MMP-1), which were considered critical for antiphotoaging. This supports our observations in the Hematoxylin and Eosin (HE) and Masson staining assay that they have a comparable effect as MSCs in terms of enhancing dermal thickness, and stimulating collagen regeneration. Although MSC-s and MSC-ex showed a weaker immunosuppression effect than MSCs, moisture measurement showed that they repair damage more rapidly than MSCs. Furthermore, the histological results showed that MSC-s maintains a super effect on immunosuppression, epidermal repair, and angiogenesis. That may be associated with the higher content of laminin, TGF-β, and VEGF in MSC-s, as well as its super cytokine transcriptional regulation ability. Thus, both MSC-s and MSC-ex can safely and effectively promote the repair of skin light injury, similar to MSCs. Our findings can broaden the range of active factors available in cell-free treatment, determine the difference between MSC-s and MSC-ex, and provide a reference for the development of similar products in regenerative medicine.

Traffic congestion is one of serious problems in cities; rainfalls would exacerbate traffic congestion, and thus result in huge economic losses. However, limited studies focused on how rainfalls influenced traffic congestion and its associated economic losses. Based on detailed hourly data, we estimated how traffic congestion index (TCI) changed with different rainfall intensities in the Beijing-Tianjin-Hebei (BTH) region, China, and we also explored their economic losses. The results illustrated that all cities presented the similar trend of daily traffic congestion, and morning peak occurred 2 hours later on holidays than workdays. Rainfall had significant impacts on traffic congestion for most time windows, except midnight. Traffic congestion increased with rainfall intensities, but smaller cities were more vulnerable to rainfall intensity than megacities. Rainfalls led to 0.98 billion yuan of extra economic losses in 2019, 38% of which occurred under heavy rainfalls. Traffic congestion in 2019 caused a total economic cost of 31.5 billion yuan in the BTH region (0.4% of its GDP), including the recurrent cost and economic losses due to rainfalls; besides, the social cost and direct cost contributed the same share of 49.4%, with 1.2% from the environmental costs. Considering future urban development and climate change, it is beneficial to establish the climate-resilient transportation system for avoiding future serious traffic congestion as well as huge economic losses in future.

As the pioneer of the Green Revolution in China, Guangdong province witnessed the improvement and spread of semi-dwarf Xian/Indica rice cultivars and possessed diverse rice germplasm of landrace and cultivars. A total of 517 accessions containing a core germplasm of 479 newly sequenced landraces and modern cultivars were used to reveal breeding signatures and key variations for regional genetic improvement of indica rice from Guangdong. Four subpopulations were identified in the collection, which including Ind IV as a novel subpopulation that not covered by previously released accessions. Modern cultivars of subpopulation Ind II were inferred to have less deleterious variations, especially in yield related genes. About 15 Mb genomic segments were identified as potential breeding signatures by cross-population likelihood method (XP-CLR) of modern cultivars and landraces. The selected regions spanning multiple yield related QTLs (quantitative trait locus) which identified by GWAS (genome-wide association studies) of the same population, and specific variations that fixed in modern cultivars of Ind II were characterized. This study highlights genetic differences between traditional landraces and modern cultivars, which revealed the potential molecular basis of regional genetic improvement for Guangdong indica rice from southern China.

Microorganisms play a vital role in human life. Therefore, microorganism detection is of great significance to human beings. However, the traditional manual microscopic detection methods have the disadvantages of long detection cycle, low detection accuracy in large orders, and great difficulty in detecting uncommon microorganisms. Therefore, it is meaningful to apply computer image analysis technology to the field of microorganism detection. Computer image analysis can realize high-precision and high-efficiency detection of microorganisms. In this review, first,we analyse the existing microorganism detection methods in chronological order, from traditional image processing and traditional machine learning to deep learning methods. Then, we analyze and summarize these existing methods and introduce some potential methods, including visual transformers. In the end, the future development direction and challenges of microorganism detection are discussed. In general, we have summarized 142 related technical papers from 1985 to the present. This review will help researchers have a more comprehensive understanding of the development process, research status, and future trends in the field of microorganism detection and provide a reference for researchers in other fields.

Hydraulic fracturing and acid fracturing are very effective stimulation technologies and are widely used in unconventional reservoir development. Fracture height, as an essential parameter to describe the geometric size of a fracture, is not only the input parameter of two-dimensional fracturing models but also the output parameter of three-dimensional fracturing models. Accurate prediction of fracture height growth can effectively avoid some risks. For example, petroleum reservoirs produce a large amount of formation water because wrong fracture height prediction leads to the connection between the oil or gas reservoir and the water layer. Although some fracture height prediction models were developed, few models considered the effects of the plastic zone, induced stress, and heterogeneous multilayer formation and its interaction. Therefore, considering the influence of many factors, an improved fracture-equilibrium-height model was developed in this study. The successive over-relaxation iteration method and the displacement discontinuity method were used to solve the model. We investigated the effects of the geological and engineering factors on fracture height growth by using the model, and some important conclusions were obtained. The higher the fracture height, the larger the plastic zone size, and the more obvious its influence on fracture height propagation. High overlying or underlying in situ stress and fracture toughness and low fluid density played a positive role in limiting the growth of the fracture height. Induced stress caused by fracture 1 could not only inhibit the height growth of fracture 2 but also promote its growth. The model established in this paper could be coupled to a fracturing simulator to provide a more reliable fracture height prediction.

Estimation bias is an important index for evaluating the performance of reinforcement learning (RL) algorithms. The popular RL algorithms, such as Q -learning and deep Q -network (DQN), often suffer overestimation due to the maximum operation in estimating the maximum expected action values of the next states, while double Q -learning (DQ) and double DQN may fall into underestimation by using a double estimator (DE) to avoid overestimation. To keep the balance between overestimation and underestimation, we propose a novel integrated DE (IDE) architecture by combining the maximum operation and DE operation to estimate the maximum expected action value. Based on IDE, two RL algorithms: 1) integrated DQ (IDQ) and 2) its deep network version, that is, integrated double DQN (IDDQN), are proposed. The main idea of the proposed RL algorithms is that the maximum and DE operations are integrated to eliminate the estimation bias, where one estimator is stochastically used to perform action selection based on the maximum operation, and the convex combination of two estimators is used to carry out action evaluation. We theoretically analyze the reason of estimation bias caused by using nonmaximum operation to estimate the maximum expected value and investigate the possible reasons of underestimation existence in DQ. We also prove the unbiasedness of IDE and convergence of IDQ. Experiments on the grid world and Atari 2600 games indicate that IDQ and IDDQN can reduce or even eliminate estimation bias effectively, enable the learning to be more stable and balanced, and improve the performance effectively.

Overexpression of nuclear coactivator steroid receptor coactivator 1 (SRC-1) and aberrant activation of the Hedgehog (Hh) signaling pathway are associated with various tumorigenesis; however, the significance of SRC-1 in colorectal cancer (CRC) and its contribution to the activation of Hh signaling are unclear. Here, we identified a conserved Hh signaling signature positively correlated with SRC-1 expression in CRC based on TCGA database; SRC-1 deficiency significantly inhibited the proliferation, survival, migration, invasion, and tumorigenesis of both human and mouse CRC cells, and SRC-1 knockout significantly suppressed azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CRC in mice. Mechanistically, SRC-1 promoted the expression of GLI family zinc finger 2 (GLI2), a major downstream transcription factor of Hh pathway, and cooperated with GLI2 to enhance multiple Hh-regulated oncogene expression, including Cyclin D1, Bcl-2, and Slug. Pharmacological blockages of SRC-1 and Hh signaling retarded CRC progression in human CRC cell xenograft mouse model. Together, our studies uncover an SRC-1/GLI2-regulated Hh signaling looping axis that promotes CRC tumorigenesis, offering an attractive strategy for CRC treatment.