Abstract
Block A is a 2016-2017 production block. After infilling, block 1,2 and 3 are divided into three segments, block 4 is divided into two segments, block 4 is divided into two segments, and ...block 4 is not divided into segments, that is, Gaotaizi first segment. With the increase of well pattern density and the increase of vertical upper strata, the whole injection-production relationship becomes more complex and the dynamic adjustment is more difficult. By integrating the static data, we can determine the dominant wells and the dominant zones among the well groups, and find out the dominant channel of each zone by comparing the seepage capacity in each direction of the water coming from the sub-zone. To further subdivide the connecting types, and finally determine the dominant channel of each sedimentary unit by combining the reservoir thickness, well spacing and source direction. For the case of multiple well patterns interacting with each other, aiming at the sections of the dominant wells and formations which are in the front of the sequence and are easy to be overinjected. For the interval in the middle of the sequence of dominant wells and formations, the water injection volume fluctuates frequently and needs to be checked and matched. For the interval in which the sequence of dominant wells and formations is backward, the measures of increasing injection are adopted. It has important guiding significance for efficient development of Gaotaizi reservoir in the later stage of ultra-high water cut.
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.
Coronaviruses (CoVs) have formerly been regarded as relatively harmless respiratory pathogens to humans. However, two outbreaks of severe respiratory tract infection, caused by the severe acute ...respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), as a result of zoonotic CoVs crossing the species barrier, caused high pathogenicity and mortality rates in human populations. This brought CoVs global attention and highlighted the importance of controlling infectious pathogens at international borders. In this review, we focus on our current understanding of the epidemiology, pathogenesis, prevention, and treatment of SARS-CoV and MERS-CoV, as well as provides details on the pivotal structure and function of the spike proteins (S proteins) on the surface of each of these viruses. For building up more suitable animal models, we compare the current animal models recapitulating pathogenesis and summarize the potential role of host receptors contributing to diverse host affinity in various species. We outline the research still needed to fully elucidate the pathogenic mechanism of these viruses, to construct reproducible animal models, and ultimately develop countermeasures to conquer not only SARS-CoV and MERS-CoV, but also these emerging coronaviral diseases.
Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It is unclear whether ...convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. Rhesus macaques reinfected with the identical SARS-CoV-2 strain during the early recovery phase of the initial SARS-CoV-2 infection did not show detectable viral dissemination, clinical manifestations of viral disease, or histopathological changes. Comparing the humoral and cellular immunity between primary infection and rechallenge revealed notably enhanced neutralizing antibody and immune responses. Our results suggest that primary SARS-CoV-2 exposure protects against subsequent reinfection in rhesus macaques.
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•HBN and CBN were added to the epoxy resin as binary nanofillers.•The BN nanoparticles modified by polydopamine displayed great dispersibility.•The tribological mechanisms of HBN and ...CBN were systematically studied.
Hexagonal boron nitride and cubic boron nitride were modified by polydopamine to improve dispersion in epoxy resin (EP). The average coefficient of friction (COF) of EP-HBN@PDA coating decreased under dry and seawater condition compared to EP indicating BN possessed self-lubricating effect. COF decreased with CBN content raising in seawater, because seawater removed debris including BN particles and CBN with high hardness improved rigidity of coatings. Wear rates of EP-CBN@PDA coating decreased by 68.88% and 97.95% compared to EP-HBN@PDA, and binary-filled coating performed excellently under seawater, it revealed CBN was more effective than HBN in improving load carrying capacity of coatings.
Graphene nanosheets are impermeable to chemical molecules and electrical conductivity. Thus, they are attractive candidates to enhance an epoxy zinc rich coating with a significant anticorrosion ...performance. Several studies focus on investigating the role of graphene in reinforcing the corrosion resistance of the coatings. However, there is a paucity of study that analyzing the anticorrosion relationship between the feature of graphene and epoxy zinc rich coating. The present study reported on epoxy zinc rich coatings with enhanced anticorrosion performance via embedding reduced graphene oxide/graphene oxide (rGO/GO) nanosheets. Thus, rGO and GO were prepared from natural graphite powder via the modified Hummers method. The results of Raman, XPS, FT-IR, SPM, and TEM analyses revealed the quintessential structure and morphology of rGO and GO. In addition, results from electrochemical measurements and the scanning vibrating electrode technique indicated that rGO effectively enhanced the cathodic protection duration of epoxy zinc rich coatings. rGO nanosheets exhibited dual functions that were identified in two aspects. First, the impermeable barrier role was exerted by including prepared rGO nanosheets into the polymer matrix. Second, superior electrical conductivity was utilized since the rGO nanosheets improved the efficiency of the electrical connection between the zinc particles and steel substrate.
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•Well-designed rGO nanosheets were used for enhancing anticorrosion.•rGO can enhance the cathodic protection duration of epoxy zinc rich coating.•rGO endowed composite coating exhibited optimal anticorrosion capability.•SVET confirmed the cathodic protection property of the coating.
As a typical machine olfactory system index, the accuracy of hybrid gas identification and concentration detection is low. This paper proposes a novel hybrid gas identification and concentration ...detection method. In this method, Kernel Principal Component Analysis (KPCA) is employed to extract the nonlinear mixed gas characteristics of different components, and then K-nearest neighbour algorithm (KNN) classification modelling is utilized to realize the recognition of the target gas. In addition, this method adopts a multivariable relevance vector machine (MVRVM) to regress the multi-input nonlinear signal to realize the detection of the concentration of the hybrid gas. The proposed method is validated by using CO and CH₄ as the experimental system samples. The experimental results illustrate that the accuracy of the proposed method reaches 98.33%, which is 5.83% and 14.16% higher than that of principal component analysis (PCA) and independent component analysis (ICA), respectively. For the hybrid gas concentration detection method, the CO and CH₄ concentration detection average relative errors are reduced to 5.58% and 5.38%, respectively.
Novel two-dimensional (2D) Nb
2
C nanosheets were successfully prepared through a simple lultrasonic and magnetic stirring treatment from the original accordion-like powder. To further study their ...water-lubrication properties and deal with common oxidation problems, Nb2C nanosheets with different oxidation degrees were prepared and achieved long-term stability in deionized water. Scanning electron microscope (SEM), transmission electron microscope (TEM), scanning probe microscope (SPM), X-ray powder diffraction (XRD), Raman, and X-ray photoelectron spectrometer (XPS) experiments were utilized to characterize the structure, morphology, and dispersion of Nb
2
C nanosheets with different degrees of oxidation. The tribological behaviors of Nb
2
C with different degrees of oxidation as additives for water lubrication were characterized using a UMT-3 friction testing machine. The wear scars formed on the 316 steel surface were measured using three-dimensional (3D) laser scanning confocal microscopy. The tribological results showed that a moderately oxidized Nb
2
C nanosheet, which owned the composition of Nb
2
C/Nb
2
O
5
/C, displayed excellent tribological performance, with the friction coefficient (COF) decreasing by 90.3% and a decrease in the wear rate by 73.1% compared with pure water. Combining the TEM and Raman spectra, it was shown that Nb
2
O
5
nanoparticles filled in the worn zone, and the layered Nb
2
C and C were adsorbed into the surface of the friction pair to form a protective lubricating film. This combined action resulted in an excellent lubricating performance.
The scanning vibration mirror system drives the scanning mirror fixed to it through the oscillation of the motor shaft, so as to control the reflected light to form a dynamic variable light path. The ...vibration mirror scanning system has higher controllability than the fixed optical path system and has been widely used.In this dissertation, after establishing the models of the core components of the scanning vibration mirror system, the mathematical model of the whole system is established.On this basis, simulation and theoretical analysis show that the system has some shortcomings, such as small bandwidth, low dynamic tracking accuracy, and the comprehensive dynamic performance of the system is easily affected by the input of external interference branches. A series correction controller and three closed-loop controller are designed for the above problems, respectively, and the control effects of the two controllers on the scanning vibration mirror system are studied through simulation experiments. By comparing the output response results of the system under the action of sinusoidal signals of different frequencies, it can be seen that the comprehensive effect of the three closed-loop controllers is better. Under the action of step signals, the overshoot of the three closed-loop correction controller correction system is 21.5% higher than that of the series controller correction system, the adjustment time is 82.7% less, and the steady-state error is significantly smaller. Therefore, it indicates that the three closed-loop correction system has good rapidity and steady-state accuracy.
Understanding how potent neutralizing antibodies (NAbs) inhibit SARS-CoV-2 is critical for effective therapeutic development. We previously described BD-368-2, a SARS-CoV-2 NAb with high potency; ...however, its neutralization mechanism is largely unknown. Here, we report the 3.5-Å cryo-EM structure of BD-368-2/trimeric-spike complex, revealing that BD-368-2 fully blocks ACE2 recognition by occupying all three receptor-binding domains (RBDs) simultaneously, regardless of their “up” or “down” conformations. Also, BD-368-2 treats infected adult hamsters at low dosages and at various administering windows, in contrast to placebo hamsters that manifested severe interstitial pneumonia. Moreover, BD-368-2’s epitope completely avoids the common binding site of VH3-53/VH3-66 recurrent NAbs, evidenced by tripartite co-crystal structures with RBDs. Pairing BD-368-2 with a potent recurrent NAb neutralizes SARS-CoV-2 pseudovirus at pM level and rescues mutation-induced neutralization escapes. Together, our results rationalized a new RBD epitope that leads to high neutralization potency and demonstrated BD-368-2’s therapeutic potential in treating COVID-19.
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•BD-368-2 blocks all three ACE2 binding sites regardless of RBD spatial conformations•BD-368-2 treats severely infected hamsters at low dosages and various dose windows•New cocktail design based on BD-368-2 neutralizes escaping SARS-CoV-2 mutants
Du et al. showed how a potent COVID-19 antibody, BD-368-2, interacts with the SARS-CoV-2 spike trimer to neutralize the virus and effectively treat severely infected hamsters. They further demonstrated how BD-368-2 can be paired with additional antibodies to form a cocktail that prevents the evolution of viral escape mutants.
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