Miracle-dz/UniFAR-FTUs huggingface dataset:
PD-1/LAG-3 bispecific antibody potentiates T cell activation and increases antitumor efficacy

Several clinical studies demonstrate that there exist other immune checkpoints overexpressed in some PD-1 inhibitor-resistant tumor patients. Among them, Lymphocyte-activation gene 3 (LAG-3) is one of the important immune checkpoint molecules and has been clinically demonstrated to have synergistic anti-tumor effects in combination with PD-1 antibody. In this study, we designed a novel ‘knob-in-hole’ PD-1/LAG-3 bispecific antibody (BsAb) YG-003D3. In conclusion, the BsAb maintained the similar affinity and thermal stability to the parental antibody, and the BsAb structure can be independent of each other in the process of double-target recognition, and the recognition activity will not be affected. Moreover, the BsAb can not only target PD-1 and LAG-3 on single cell simultaneously, but also bridge the two kinds of cells expressing PD-1 and LAG-3, so as to release the ‘brake system of immune checkpoints’ and activate immune cells to exert anti-tumor effects more effectively. Especially in the PBMCs activation assay, YG-003D3 induced stronger IFN-γ, IL-6, and TNF-α secretion compared to anti-PD-1 or anti-LAG-3 single drug group or even combined drug group. In the tumor killing experiment of PBMC in vitro, YG-003D3 has a better ability to activate PBMC to kill tumor cells than anti-PD-1 or anti-LAG-3 single drug group or even combined drug group, and the killing rate is as high as 20%. In a humanized PD-1/LAG-3 transgenic mouse subcutaneous tumor-bearing model, YG-003D3 showed good anti-tumor activity, even better than that of the combination group at the same molar concentration. Further studies have shown that YG-003D3 could significantly alter the proportion of immune cells in the tumor microenvironment. In particular, the proportion of CD45+, CD3+ T, CD8+ T cells in tumor tissue and the proportion of CD3+ T, CD8+ T, CD4+ T cells in peripheral blood were significantly increased. These results suggest that YG-003D3 exerts a potent antitumor effect by activating the body ‘s immune system. In summary, the BsAb YG-003D3 has good anti-tumor activity, which is expected to become a novel drug candidate for cancer immunotherapy.
The influence of the interaction between platform types and consumer types on the purchase intention of live streaming

Under the background of the rapid development of live streaming shopping industry, diversified live streaming platforms have emerged one after another. This study aims to explore the interaction effect of platform types (live streaming embedded in e-commerce platforms/LSEEC vs. e-commerce integrated into live streaming platforms/ECILS) and consumer types (goal-driven consumers vs. recreational consumers) on purchase intention. To verify the effect, this study firstly conducted a laboratory experiment (Study 1), and then carried out a questionnaire survey through the Internet (Study 2). The results indicate that the interaction effect of platform types and consumer types exists (Study 1) and thinking patterns play a mediating role (Study 2): for goal-driven consumers, LSEEC platforms are more likely to stimulate their rational thinking and enhance their purchase intention; for recreational consumers, ECILS platforms are more likely to stimulate their emotional thinking and enhance their purchase intention. The findings expand the depth of research related to live streaming platforms, deepen the understanding of the thinking patterns in live streaming shopping decision-making, and have certain guiding significance for the strategic formulation of enterprises.
Recent advances in sustainable and safe marine engine operation with alternative fuels

Pursuing net-zero emission operations in the shipping industry are quintessential for this sector to mitigate the environmental impact caused by hydrocarbon fuel combustion. Significant contributions to this are expected from the substitution of conventional marine fuels by alternative, emission-free fuels with lower emission footprints. This study aims to conduct a comprehensive literature review for delineating the main characteristics of the considered alternative fuels, specifically focusing on hydrogen, methanol, and ammonia, which have recently attracted attention from both industry and academia. This study comparatively assesses the potential of using these fuels in marine engines, and their subsequent performance characteristics as well as the associated environmental benefits. In addition, the required storage conditions, space, as well as the associated costs, are reviewed. Special attention is given to the safety characteristics and requirements for each alternative fuel. The results of this study demonstrate that the environmental benefits gained from alternative fuel use are pronounced only when renewable energy is considerably exploited for their production, whereas the feasibility of each fuel depends on the vessel type used and pertinent storage constraints. Hydrogen, ammonia, and methanol are considered best-fit solutions for small scale shipping, requiring minimal on-board storage. In addition, the need for comparative assessments between diesel and alternative fuels is highlighted and sheds light on marine engines’ operational characteristics. Moreover, using combinations of alternative and diesel fuels is identified as a direction towards decarbonisation of the maritime sector; intensifying the need for optimisation studies on marine engine design and operation. This study concludes with recommendations for future research directions, thus contributing to fuel research concepts that can facilitate the shipboard use of alternative fuels.
An update on angiotensin-converting enzyme 2 structure/functions, polymorphism, and duplicitous nature in the pathophysiology of coronavirus disease 2019: Implications for vascular and coagulation disease associated with severe acute respiratory syndrome coronavirus infection

It has been known for many years that the angiotensin-converting enzyme 2 (ACE2) is a cell surface enzyme involved in the regulation of blood pressure. More recently, it was proven that the severe acute respiratory syndrome coronavirus (SARS-CoV-2) interacts with ACE2 to enter susceptible human cells. This functional duality of ACE2 tends to explain why this molecule plays such an important role in the clinical manifestations of coronavirus disease 2019 (COVID-19). At the very start of the pandemic, a publication from our Institute (entitled “ACE2 receptor polymorphism: susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome”), was one of the first reviews linking COVID-19 to the duplicitous nature of ACE2. However, even given that COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin system (RAS), we were still far from understanding the complexity of the mechanisms which are controlled by ACE2 in different cell types. To gain insight into the physiopathology of SARS-CoV-2 infection, it is essential to consider the polymorphism and expression levels of the ACE2 gene (including its alternative isoforms). Over the past 2 years, an impressive amount of new results have come to shed light on the role of ACE2 in the pathophysiology of COVID-19, requiring us to update our analysis. Genetic linkage studies have been reported that highlight a relationship between ACE2 genetic variants and the risk of developing hypertension. Currently, many research efforts are being undertaken to understand the links between ACE2 polymorphism and the severity of COVID-19. In this review, we update the state of knowledge on the polymorphism of ACE2 and its consequences on the susceptibility of individuals to SARS-CoV-2. We also discuss the link between the increase of angiotensin II levels among SARS-CoV-2-infected patients and the development of a cytokine storm associated microvascular injury and obstructive thrombo-inflammatory syndrome, which represent the primary causes of severe forms of COVID-19 and lethality. Finally, we summarize the therapeutic strategies aimed at preventing the severe forms of COVID-19 that target ACE2. Changing paradigms may help improve patients’ therapy.
Processes and mechanisms of vegetation ecosystem responding to climate and ecological restoration in China

Vegetation is an essential component of the earth’s surface system and its dynamics is a clear indicator of global climate change. However, the vegetation trends of most studies were based on time-unvarying methods, cannot accurately detect the long-term nonlinear characteristics of vegetation changes. Here, the ensemble empirical mode decomposition and the Breaks for Additive Seasonal and Trend algorithm were applied to reconstruct the the normalized difference vegetation index (NDVI) data and diagnose spatiotemporal evolution and abrupt changes of long-term vegetation trends in China during 1982–2018. Residual analysis was used to separate the influence of climate and human activities on NDVI variations, and the effect of specific human drivers on vegetation growth was obtained. The results suggest that based on the time-varying analysis, high vegetation browning was masked by overall vegetation greening. Vegetation growth in China experienced an abrupt change in the 1990s and 2000s, accounting for 50% and 33.6% of the whole China respectively. Of the area before the breakpoint, 45.4% showed a trend of vegetation decrease, which was concentrated mainly in east China, while 43% of the area after the breakpoint also showed vegetation degradation, mainly in northwest China. Climate was an important driving force for vegetation change in China. It played a positive role in south China, but had a negative effect in northwest China. The impact of human activities on vegetation growthchanged from an initial negative influence to a positive one. In terms of human activities, an inverted-U-shaped relation was detected between CO2 emissions and vegetation growth; that is, the fertilization effect of CO2 had a certain threshold. Once that threshold was exceeded, it would hinder vegetation growth. Population density had a slight constraint on vegetation growth, and the implementation of ecological restoration projects (e.g., the Grain for Green Program) can promote vegetation growth to a certain extent.
Allelopathy and its application as a weed management tool: A review

Weeds are a serious threat to crop production as they interfere with the crop growth and development and result in significant crop losses. Weeds actually cause yield loss higher than any other pest in crop production. As a result, synthetic herbicides have been widely used for weed management. Heavy usage of synthetic herbicides, however, has resulted in public concerns over the impact of herbicides on human health and the environment. Due to various environmental and health issues associated with synthetic herbicides, researchers have been exploring alternative environmentally friendly means of controlling weed. Among them, incorporating allelopathy as a tool in an integrated weed management plan could meaningfully bring down herbicide application. Allelopathy is a biological phenomenon of chemical interaction between plants, and this phenomenon has great potential to be used as an effective and environmentally friendly tool for weed management in field crops. In field crops, allelopathy can be applied through intercropping, crop rotation, cover crops, mulching and allelopathic water extracts to manage weeds. Accumulating evidence indicates that some plant species possess potent allelochemicals that have great potential to be the ecofriendly natural herbicides. This review is intended to provide an overview of several allelopathic species that release some form of the potent allelochemical with the potential of being used in conventional or organic agriculture. Further, the review also highlights potential ways allelopathy could be utilized in conventional or organic agriculture and identify future research needs and prospects. It is anticipated that the phenomenon of allelopathy will be further explored as a weed management tool, and it can be a part of a sustainable, ecological, and integrated weed management system.
Design strategies for composite matrix and multifunctional polymeric scaffolds with enhanced bioactivity for bone tissue engineering

Over the past few decades, various bioactive material-based scaffolds were investigated and researchers across the globe are actively involved in establishing a potential state-of-the-art for bone tissue engineering applications, wherein several disciplines like clinical medicine, materials science, and biotechnology are involved. The present review article’s main aim is to focus on repairing and restoring bone tissue defects by enhancing the bioactivity of fabricated bone tissue scaffolds and providing a suitable microenvironment for the bone cells to fasten the healing process. It deals with the various surface modification strategies and smart composite materials development that are involved in the treatment of bone tissue defects. Orthopaedic researchers and clinicians constantly focus on developing strategies that can naturally imitate not only the bone tissue architecture but also its functional properties to modulate cellular behaviour to facilitate bridging, callus formation and osteogenesis at critical bone defects. This review summarizes the currently available polymeric composite matrices and the methods to improve their bioactivity for bone tissue regeneration effectively.
Commentary: A GSH/CB dual-controlled self-assembled nanomedicine for high-efficacy doxorubicin-resistant breast cancer therapy

With great interest, we read the paper A GSH/CB dual-controlled self-assembled nanomedicine for high-efficacy doxorubicin-resistant breast cancer therapy published in the Frontiers in Pharmacology (Yang et al., 2021). In the study, Yang et al developed a glutathione (GSH)/cathepsin B (CB) dual-controlled precursor of a cyclic disulfidebridged peptide (cyclic-1a). It could form a supramolecular hydrogel to overcome the drug resistance in breast cancer. Overall, this is an excellent study, but some issues need to be discussed here. In Yang’s report, the human breast cancer MCF7 cells were used to determine the anticancer efficacy of cyclic-1a. The results showed that various concentrations of cyclic1a promoted the apoptosis of MCF-7 doxorubicin resistant cells in a dose-dependent manner. Moreover, the total caspase-3 protein markedly down-regulated, while cleaved caspase-3 protein up-regulated significantly after treatment with cyclic-1a (Figure 4C and Figure 5E). However, it is well known that theMCF-7 cells do not express caspase-3 (Jänicke et al., 1998; Friedrich et al., 2001; Ferguson et al., 2003; Jänicke, 2009). The lack of caspase-3 in MCF-7 cells is caused by a forty-seven base pair deletion within exon 3 of the CASP-3 gene. It leads to skip the exon during pre-mRNA splicing and introduce a premature stop OPEN ACCESS
A comprehensive review of drying meat products and the associated effects and changes

Preserving fresh food, such as meat, is significant in the effort of combating global food scarcity. Meat drying is a common way of preserving meat with a rich history in many cultures around the globe. In modern days, dried meat has become a well enjoyed food product in the market because of its long shelf-life, taste and health benefits. This review aims to compile information on how the types of meat, ingredients and the used drying technologies influence the characteristics of dried meat in physicochemical, microbial, biochemical and safety features along with technological future prospects in the dried meat industry. The quality of dried meat can be influenced by a variety of factors, including its production conditions and the major biochemical changes that occur throughout the drying process, which are also discussed in this review. Additionally, the sensory attributes of dried meat are also reviewed, whereby the texture of meat and the preference of the market are emphasized. There are other aspects and concerning issues that are suggested for future studies. It is well-known that reducing the water content in meat helps in preventing microbial growth, which in turn prevents the presence of harmful substances in meat. However, drying the meat can change the characteristics of the meat itself, making consumers concerned on whether dried meat is safe to be consumed on a regular basis. It is important to consider the role of microbial enzymes and microbes in the preservation of their flavor when discussing dried meats and dried meat products. The sensory, microbiological, and safety elements of dried meat are also affected by these distinctive changes, which revolve around customer preferences and health concerns, particularly how drying is efficient in eliminating/reducing hazardous bacteria from the fish. Interestingly, some studies have concentrated on increasing the efficiency of dried meat production to produce a safer range of dried meat products with less effort and time. This review compiled important information from all available online research databases. This review may help the food sector in improving the efficiency and safety of meat drying, reducing food waste, while maintaining the quality and nutritional content of dried meat.
Dynamic Deep Learning ?

The standard approach to deep learning has been first to design the network architecture manually, then train the network with data. Architecture design remains an art that requires manual input by machine-learning experts. A number of methods have been suggested for automating architecture design. Among the earliest dynamic models, one finds the cascade-correlation architecture [3], which adds one hidden neuron at a time while freezing the network to avoid catastrophic forgetting. Progressive neural networks [6] add new layers of neurons successively while blocking changes to those parts of the network that were trained on earlier data, so that previously acquired knowledge is retained. Other incremental methods exist: e.g., based on incremental training of an autoencoder whereby neurons are added either in response to high failure rate with new data [7] or based on reconstruction error [2]. AdaNet [1] gradually extends its network based on evaluation and selection among candidate sub-networks. A dynamically expandable network [4] expands its capacity via network split and duplication operations, retraining the old network only when necessary. Despite the advent of such methods, architecture design remains on the whole a manual exercise based on some predefined heuristics. Moreover, these methods tend to be computationally inefficient, involving extensive search among alternative architectures or repeated training of dense architectures with randomly initialized parameters. We propose a principled dynamic approach for deep learning that starts as a blank slate and develops a deep neural network gradually, in a fully automatic and energy-efficient manner.
Proper orthogonal decomposition methods for noise reduction in particle-based transport calculations

Proper orthogonal decomposition techniques to reduce noise in the reconstruction of the distribution function in particle-based transport calculations are explored. For two-dimensional steady-state problems, the method is based on low rank truncations of the singular value decomposition of a coarse-grained representation of the particle distribution function. For time-dependent two-dimensional problems or three-dimensional time-independent problems, the use of a generalized low-rank approximation of matrices technique is proposed. The methods are illustrated and tested with Monte Carlo particle simulation data of plasma collisional relaxation and guiding-center transport with collisions in a magnetically confined plasma in toroidal geometry. It is observed that the proposed noise reduction methods achieve high levels of smoothness in the particle distribution function by using significantly fewer particles in the computations.
A Novel Visual Servoing Approach For Keeping Feature Points Within The Field-at-View

In this paper, an eye-in-hand visual servoing strategy for keeping feature points within the FOV(field-of-view) is proposed. We first specify the FOV constraint which must be satisfied to keep the feature points within the FOV. It is expressed as the inequality relationship between (ⅰ) the LOS(line-of-sight) angles of the center of the feature points from the optical axis of the camera and (ⅱ) the distance between the object and the camera. We then design a nonlinear feedback controller which decouples linearly the translational and rotational control loops. Finally, we show that appropriate choice of the controller gains assures to satisfy the FOV constraint. The main advantage of our approach over the previous ones is that the trajectory of the camera is smooth and circular-like. Furthermore, ours can be applied to the large camera displacement problem.
Robust H
∞ Control in Fast Atomic Force Microscopy

This paper develops a robust H ∞ method for fast tracking position control problems arising in an atomic force microscope (AFM). A commercial type NT‐MDT AFM is used to generate 3D images of scanned material surfaces at high speeds and accuracies. A major component of this AFM is a piezoelectric tube actuator used for position control in three directions. Due to the nature of the piezoelectric actuator, there is nonlinear hysteresis present which affects the AFM scanning qualities. The original commercial AFM uses traditional proportional‐integral‐derivative position control and can only obtain good quality images for scanning rates under about 20 Hz in both the x and y directions.
Aeroacoustic computations using a high-order shock-capturing scheme

For aeroacoustic computations in the supersonic regime, it is necessary to use a numerical scheme that can represent shock waves without generating spurious numerical oscillations. The centered schemes that are usually used with success in the subsonic case, combined with a selective filtering, will generally oscillate in the presence of discontinuities. A new class of shock-capturing schemes, the one-step monotonicity-preserving schemes, combine the high accuracy and the nonoscillating property. It is thus a good candidate for supersonic aeroacoustic applications. The good spectral properties of these schemes are illustrated in the scalar linear case. Results of aeroacoustic test problems for the Euler and Navier-Stokes equations are compared with a dispersion-relation-preserving scheme. The application to a supersonic cavity flow, which induces a complex pattern of moving shocks, shows that the one-step monotonicity-preserving schemes capture the moving discontinuities without spurious oscillations and preserve a high accuracy at the same time.
Collective Modes of Photoexcited Electron-Hole Plasmas in GaAs

Light scattering spectra of photoexcited electron-hole plasmas in GaAs show features due to the multicomponent nature of the plasma, and also specific to the presence of holes. At low energies, \ensuremath{\sim}5 meV, we observe a Landau-damped acoustic plasma mode. At higher energies inter-valence-band transitions of the photoexcited holes modify the spectra of coupled optic-plasmon-LO-phonon modes.