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Abstract The SARS-CoV-2 Omicron variant evades most currently approved neutralizing antibodies (nAbs) and caused drastic decrease of plasma neutralizing activity elicited by vaccination or prior infection, urging the need for the development of pan-variant antivirals. Breakthrough infection induces a hybrid immunological response with potentially broad, potent and durable protection against variants, therefore, convalescent plasma from breakthrough infection may provide a broadened repertoire for identifying elite nAbs. We performed single-cell RNA sequencing (scRNA-seq) and BCR sequencing (scBCR-seq) of B cells from BA.1 breakthrough-infected patients who received 2 or 3 previous doses of inactivated vaccine. Elite nAbs, mainly derived from the IGHV2–5 and IGHV3-66/53 germlines, showed potent neutralizing activity across Wuhan-Hu-1, Delta, Omicron sublineages BA.1 and BA.2 at picomolar NT50 values. Cryo-EM analysis revealed diverse modes of spike recognition and guides the design of cocktail therapy. A single injection of paired antibodies cocktail provided potent protection in the K18-hACE2 transgenic female mouse model of SARS-CoV-2 infection.

Abstract Inspired by the cartilage-bone structure in natural joints, soft-hard integrated materials have received extensive attention, which are the most promising candidates for artificial joints due to their combination of excellent load-bearing properties and lubricating properties. The latest progress showed that the combination of hydrogel and titanium alloy can realize a bionic natural joint lubrication system on the surface of titanium alloy. However, obtaining a tough interface between the hydrogel (soft and wet) and the titanium substrate (hard and dry) is still a great challenge. Here, we designed a “soft (hydrogel)-hard (Ti6Al4V)” integrated material with outstanding combination, which simulates the structure and function of cartilage-bone in the natural joint. The load-bearing properties, binding performance, and tribological behaviors for different forms of the soft-hard integrated materials were investigated. The results showed that the hydrogel layer and Ti6Al4V substrate possess ultra-high interfacial toughness (3,900 J/m2). In addition, the combination of the hydrogel layer and Ti6Al4V substrate provided a good lubrication system to endow the “soft (hydrogel)-hard (Ti6Al4V)” integrated material with high load-bearing and excellent tribological properties. Therefore, this study provided an effective strategy for prolonging the service life of Ti6Al4V in the biomedical field.

Acute myeloid leukemia (AML) and T cell acute lymphoblastic leukemia (T-ALL) are two of the most prevalent hematological malignancies diagnosed among adult leukemia patients, with both being difficult to treat and associated with high rates of recurrence and mortality. In the present study, bioinformatics approaches were used to analyze both of these types of leukemia in an effort to identify characteristic gene expression patterns that were subsequently validated via Raman spectroscopy. For these analyses, four Gene Expression Omnibus datasets (GSE13204, GSE51082, GSE89565, and GSE131184) pertaining to acute leukemia were downloaded, and differentially expressed genes (DEGs) were then identified through comparisons of AML and T-ALL patient samples using the R Bioconductor package. Shared DEGs were then subjected to Gene Ontology (GO) enrichment analyses and were used to establish a protein-protein interaction (PPI) network analysis. In total, 43 and 129 upregulated and downregulated DEGs were respectively identified. Enrichment analyses indicated that these DEGs were closely tied to immune function, collagen synthesis and decomposition, inflammation, the synthesis and decomposition of lipopolysaccharide, and antigen presentation. PPI network module clustering analyses further led to the identification of the top 10 significantly upregulated and downregulated genes associated with disease incidence. These key genes were then validated in patient samples via Raman spectroscopy, ultimately confirming the value of these genes as tools that may aid the differential diagnosis and treatment of AML and T-ALL. Overall, these results thus highlight a range of novel pathways and genes that are linked to the incidence and progression of AML and T-ALL, providing a list of important diagnostic and prognostic molecular markers that have the potential to aid in the clinical diagnosis and treatment of these devastating malignancies.

Nasopharyngeal carcinoma (NPC) is a type of head and neck tumor with noticeable regional and ethnic differences. It is associated with Epstein-Barr virus infection and has a tendency for local and distant metastasis. NPC is also highly sensitive to radiotherapy and chemotherapy. Over 70% of patients present with locoregionally advanced disease, and distant metastasis is the primary reason for treatment failure. A signal transducer and activator of transcription 3 (STAT3) promotes NPC oncogenesis through mechanisms within cancerous cells and their interactions with the tumor microenvironment, which is critical in the initiation, progression, and metastasis of NPC. Further, p-STAT3 is strongly associated with advanced NPC. Recent research on STAT3 has focused on its expression at the center of various oncogenic pathways. Here, we discuss the role of STAT3 in NPC and its potential therapeutic inhibitors and analogs for the treatment and control of NPC.

Xinjiang is one of the world’s most sensitive and vulnerable regions to climate change. However, little is known about the current status and changes in thermal comfort conditions in this area. Using the Universal Thermal Climate Index (UTCI) derived from the newly available high-resolution dataset HiTiSEA, the spatial–temporal pattern and changes thereof over annual and seasonal scales across Xinjiang from 1981 to 2019 were evaluated. The results reveal that the distribution and change of thermal comfort in Xinjiang have apparent regional heterogeneity and seasonal characteristics. Across all scales, 7 of 10 UTCI thermal stress categories were observed, from slight cold stress to strong heat stress. Annually, the mean UTCI is 3 °C and has significantly increased at 0.37 °C decade−1. The mean number of comfortable days (CDs) is 114 days, with a range from 0 to 189 days. On the space scale, the Tarim Basin experiences the highest UTCI value, while the Ili River Valley, the north side of the Tianshan Mountains, and the peripheral areas of the Tarim Basin have a higher number of CDs. Seasonally, summer has the highest UTCI value, while winter is the lowest. The trend for all seasons is upward, and spring increases fastest. Results also indicate that air temperature has a positive correlation with climate comfort, and the influence of air temperature on climate comfort is most significant. Further research indicates that the range and intensity of population exposure to uncomfortable climates in Xinjiang have increased. The distribution and expansion of population exposure are similar to the population density. These findings contribute to a systematic understanding of the local climate environment and can be helpful for the assessment of the impact of climate change and optimize tourism development.

The antioxidant enzyme system is the main defense system responsible for maintaining cellular reactive oxygen species (ROS) homeostasis and normal plant growth and development after saline stress. In this study, we identified and characterized the members of the SOD, APX and CAT gene families of the antioxidant enzyme system in Gymnocarpos przewalskii, using plant physiology and molecular biology methods, and analyzed the pattern of enzyme activity in response to NaCl stress. It was found that seven, six and two genes of SOD, APX and CAT gene families, respectively, were expressed in the leaf tissue of G. przewalskii, in which most of the genes were significantly upregulated under NaCl stress, and the enzymatic activities were in accordance with the gene expression. Three positive selection sites in the GpCAT1 gene can increase the hydrophilicity of the GpCAT1 protein, increase the volume of the active site and increase the affinity for H2O2, thus improving the catalytic efficiency of GpCAT1. The results of the present study provide new insights for further investigations of the evolution and function of the SOD, APX and CAT gene families in G. przewalskii and their essential roles under salt stress, and the findings will be useful for revealing the molecular mechanism of salt tolerance and breeding of salt-tolerant plants.

Purpose: The central nervous mechanism of acute tinnitus is different from that of chronic tinnitus, which may be related to the difference of cerebral blood flow (CBF) perfusion in certain regions. To verify this conjecture, we used arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) in this study to compare the CBF alterations of patients with acute and chronic tinnitus.Methods: The current study included patients with chronic tinnitus (n = 35), acute tinnitus (n = 30), and healthy controls (n = 40) who were age-, sex-, and education-matched. All participants underwent MRI scanning and then ASL images were obtained to measure CBF of the entire brain and analyze the differences between groups as well as the correlations with tinnitus characteristics.Results: The chronic tinnitus group showed increased z-CBF in the right superior temporal gyrus (STG) and superior frontal gyrus (SFG) when compared with the acute tinnitus patients. Further connectivity analysis found enhanced CBF connectivity between the right STG and fusiform gyrus (FG), the right SFG and left middle occipital gyrus (MOG), as well as the right parahippocampal gyrus (PHG). Moreover, in the chronic tinnitus group, the tinnitus handicap questionnaire (THQ) score was positively correlated with the normalized z-CBF of right STG (r = 0.440, p = 0.013).Conclusion: Our results confirmed that the CBF changes in some brain regions were different between acute and chronic tinnitus patients, which was correlated with certain tinnitus characteristics. This is of great value to further research on chronicity of tinnitus, and ASL has a promising application in the measurement of CBF.

Globally, mountains have suffered enormous biodiversity loss and habitat degradation due to climate change and human activities. As an agent of biodiversity, evaluating habitat quality (HQ) change is an indispensable key step for regional ecological security and human well-being enhancement, especially for fragile mountain ecosystems in arid areas. In this study, we aimed to propose an integrated framework coupled with the Normalized Difference Vegetation Index (NDVI) and Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST)-HQ module to improve the effectiveness and accuracy of HQ estimation. We highlighted the Tianshan Mountains in Xinjiang as an example to validate the model, as it is a typical representative of mountain ecosystems in the temperate arid zone. Specifically, we aimed to assess the spatiotemporal dynamics of HQ over the past two decades and investigate its influencing factors using a geographical detector model. The results show that, first, grassland and unused land were the main land-use types in the study area. The land-use transitions were mainly concentrated in grassland, woodland, water body, and unused land. Second, the total area of very important habitats and general habitats accounted for over 70% of the Tianshan Mountains. The average HQ decreased from 0.5044 to 0.4802 during 1995–2015. Third, the HQ exhibited significant spatial differentiation, and the Ili River Valley and Kaidu River Basin were the hot spots, while the south and east of the Tianshan Mountains were the cold spots. Habitat quality was strongly related to the terrain gradient, with an inverted “U” type. Protected areas of different categories played a vital role in biodiversity conservation. Finally, soil type, land-use change, precipitation, temperature, and grazing intensity were the dominant factors in response to HQ change for both the total Tianshan Mountains and sub-regions, followed by elevation, the relief degree of the land surface, gross domestic product, population density, and distance to tourism attractions. The interaction effects of the influencing factors were improved compared to the effects of the individual factors in each zone. Furthermore, these results provide decision-making criteria for formulating a scientific and systematic protection of ecology and restoration planning systems to enhance the capacity to address climate change.

The difference of multi-label classification from traditional classification is that an instance may associate a set of labels simultaneously. In recent study, some scholars have proposed that the information which derives from the query instance's nearest neighbors, can be useful when predicting the labels of the query instance. On the basis of their research, we propose a new approach to multi-label classification, which employs neural tensor network (NTN) to explore the relations among the labels of neighbors and classify the query instance with these correlations. This method utilizes the correlations and interdependencies between labels and leverages the potential of data. Experiments on real data show that our method can achieve good performance in multi-label classification.

Tinnitus refers to sound perception in the absence of external sound stimulus. It has become a worldwide problem affecting all age groups especially the elderly. Tinnitus often accompanies hearing loss and some mood disorders like depression and anxiety. The comprehensive adverse effects of tinnitus on people determine the severity of tinnitus. Understanding the mechanisms of tinnitus and related discomfort may be beneficial to the prevention and treatment, and then getting patients out of tinnitus distress. Functional magnetic resonance imaging (fMRI) is a powerful technique for characterizing the intrinsic brain activity and making us better understand the tinnitus neural mechanism. In this article, we review fMRI studies published in recent years on the neuroimaging mechanisms of tinnitus. The results have revealed various neural network alterations in tinnitus patients, including the auditory system, limbic system, default mode network, attention system, and some other areas involved in memory, emotion, attention, and control. Moreover, changes in functional connectivity and neural activity in these networks are related to the perception, persistence, and severity of tinnitus. In summary, the neural mechanism of tinnitus is a complex regulatory mechanism involving multiple networks. Future research is needed to study these neural networks more accurately to refine the tinnitus models.

Taking metropolitan areas as space carriers has become the engine of the Chinese government in its promotion of high-quality development, and this has also become an important measure by which to balance regional development. We used Zipf’s law and the gravity model to study the urban scale distribution characteristics of the Kashgar Metropolitan Area (KMA) in this paper. We also constructed a spatial structure judgment vector for the KMA and put forward the development objectives of different circles. The findings show the following: (1) large cities have a high primacy of development, while small and medium-sized cities are underdeveloped. At present, the KMA is a concentrated monocentric-pattern metropolitan area, with Kashgar City as its core city. (2) The urban built-up area of Kashgar City is expanding to the east and south, where it has broken through the administrative boundary and become integrated with the urban built-up area of Shule County. The spatial structure characteristics of the KMA have been further clarified. The KMA forms three circles: core, middle, and outer. (3) Tumxuk City, Bachu County, Yecheng County, Shache County, and other counties are far from the core city and cannot be connected with Kashgar, but they are closely related to the surrounding cities, forming the Bachu–Tumxuk Urban Group and the Shache–Zepu–Yecheng Urban Group. This study contributes to the understanding of the characteristics of urban scale distribution and the spatial structure of metropolitan areas in arid regions, as well as providing guidance for the formulation of policies for the development of different circles in the KMA.

Abstract Medium manganese austenitic steel (MMAS) fabricated through the hot rolling process has been used in the mining, military, and mechanical industries. In this paper, the abrasion performance and hardening mechanism were measured under a series of impact energies. The impact wear was tested at different impact energies from 0.5 J to 6 J using a dynamic load abrasive wear tester (MLD-10). Microstructure and surface morphologies were analyzed using scanning electron microscopy, X-Ray diffraction, and transmission electron microscopy. The results suggest that MMSA has the best wear resistance at 3.5 J and the worst wear resistance at 1.5 J. Furthermore, the wear mechanism and worn surface microstructure change with different impact energies. There are small differences between a large amount of martensite on the worn surfaces under different impact energies and the shapes of dislocation and twins change with different impact energies.

Evapotranspiration (ET) estimation has been one of the most challenging problems in recent decades for hydrometeorologists. In this study, a nonparametric approach to estimate terrestrial evaporation was evaluated using both model simulation and measurements from three sites. Both the model simulation and the in situ evaluation at the Tiger Bush Site revealed that this approach would greatly overestimate ET under dry conditions (evaporative fraction smaller than 0.4). For the evaluation at the Tiger Bush Site, the difference between ET estimates and site observations could be as large as 130 W/m2. However, this approach provided good estimates over the two crop sites. The Nash-Sutcliffe coefficient (E) was 0.9 and 0.94, respectively, for WC06 and Yingke. A further theoretical analysis indicates the nonparametric approach is very close to the equilibrium evaporation equation under wet conditions, and this can explain the good performance of this approach at the two crop sites in this study. The evaluation indicates that this approach needs more careful appraisal and that its application in dry conditions should be avoided.

An algorithm was developed to expand the surface air temperature and air humidity to a larger spatial domain, based on the fact that the variation of surface air temperature and air humidity is controlled jointly by the local turbulence and the horizontal advection. This study proposed an algorithm which considers the advective driving force outside the thermal balance system and the turbulent driving force and radiant driving force inside the thermal balance system. The surface air temperature is determined by a combination of the surface observations and the regional land surface temperature observed from a satellite. The average absolute difference of the algorithm is 0.65 degree and 0.31 mb, respectively, for surface air temperature and humidity expansion, which provides a promising approach to downscale the two surface meteorological variables.

It is challenging to assimilate the evapotranspiration product (EP) retrieved from satellite data into land surface models (LSMs). In this paper, a perturbed ensemble Kalman filter (PEKF) and à trous wavelet transform (AWT) integrated method are proposed to implement the evapotranspiration assimilation. In this method, the AWT is used to decompose the EPs into multiple channels since it is very powerful in fusing high frequency spatial information of multisource data, and then the Kalman filter is performed in the AWT domain. The proposed method combines the advantages of the PEKF that is capable of accommodating model error and observation error, and the AWT can effectively perform multiresolution fusion. Assimilation experiment conducted with the Noah model and the EP retrieved from the MODIS data shows that the proposed method performs better than the traditional ensemble Kalman filter (EnKF) and PEKF methods. The analysis results fit well with the evapotranspiration observation at two field sites with different land surface conditions. These indicate that the proposed method is promising for assimilating regional scale satellite retrieved EP into LSMs.

Based on the crop water stress index (CWSI) concept, a new model was proposed to account for advection to estimate evapotranspiration. Both local scale evaluation with sites observations and regional scale evaluation with a remote dataset from Landsat 7 ETM+ were carried out to assess the performance of this model. Local scale evaluation indicates that this newly developed model can effectively characterize the daily variations of evapotranspiration and the predicted results show good agreement with the site observations. For all the 6 corn sites, the coefficient of determination (R2) is 0.90 and the root mean square difference (RMSD) is 58.52W/m2. For all the 6 soybean sites, the R2 and RMSD are 0.85 and 49.46W/m2, respectively. Regional scale evaluation shows that the model can capture the spatial variations of evapotranspiration at the Landsat-based scale. Clear spatial patterns were observed at the Landsat-based scale and are closely related to the dominant land covers, corn and soybean. Furthermore, the surface resistance derived from instantaneous CWSI was applied to the Penman-Monteith equation to estimate daily evapotranspiration. Overall, results indicate that this newly developed model is capable of estimating reliable surface heat fluxes using remotely sensed data.

Radiotherapy is widely used as the first-line treatment for nasopharyngeal carcinoma (NPC). However, the resistance of some patients to treatment lowers its clinical effectiveness. Compared to typical epithelial cells, NPC markedly lowers the Ras-association domain family 1A (RASSF1A) protein expression. RASSF1A overexpression sensitizes NPC cells to radiotherapy. Mechanistically, RASSF1A promotes the expression of Forkhead box O3a (FoxO3a) in the nucleus and inhibits the Nuclear factor E2-related factor 2 (Nrf2) signaling pathway via binding to the Kelch-like ECH-associated protein 1 (Keap1) promoter. Through elevating intracellular ROS levels, RASSF1A overexpression inhibits the expression of thioredoxin reductase 1 (TXNRD1), a crucial Nrf2 target gene, and increases NPC sensitivity to radiation. Immunohistochemical staining of NPC tissue sections revealed that the expression of RASSF1A is negatively correlated with that of TXNRD1. The traditional Chinese medicine component andrographolide (AGP), which induces RASSF1A expression, increased the sensitivity of NPC cells to radiotherapy in vitro and in vivo. Our findings implied that RASSF1A increases the sensitivity of NPC to radiation by increasing FoxO3a expression in the nucleus, inhibiting the Nrf2/TXNRD1 signaling pathway, and elevating intracellular ROS levels. AGP targets RASSF1A and may be a promising adjuvant sensitizer for enhancing radiosensitivity in NPC. [ABSTRACT FROM AUTHOR]