Lymphocytes in Patients with Chronic Active Epstein-Barr Virus Disease Exhibited Elevated PD-1/PD-L1 Expression and a Prevailing Th2 Immune Response.

Background And Objectives: Chronic active Epstein-Barr virus disease (CAEBV) is a proliferative disease of EBV+ T or natural killer (NK) cells with an unclear pathogenesis. This study aimed to examine the frequency and exhaustion levels of lymphocyte subsets in patients with CAEBV to further investigate the pathogenesis. Methods: Using flow cytometry, we detected the frequency, expression levels of programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1), and EBV infection status of peripheral T subsets and NK cells in patients with CAEBV and healthy individuals. Results: 24 patients and 15 healthy individuals were enrolled in this study. Patients showed notably higher expression levels of PD-1 and PD-L1 in peripheral T subsets and NK cells compared to healthy individuals (P < 0.05). EBV+ lymphocytes exhibited significantly higher PD-L1 expression levels than EBV- lymphocytes. Additionally, the frequency of effector memory T (Tem) cells was significantly increased in patients, and the PD-L1 expression level was positively correlated with the EBV load. Besides, helper T cell 2 (Th2) immune bias, also favoring EBV amplification, was found in patients, including increased Th2 cell frequency, enhanced response capacity, and elevated serum levels of associated cytokines. The distribution and PD-1 expression levels of peripheral T subsets returned to normal in patients who responded to PD-1 blockade therapy. Conclusions: The up-regulation of the PD-1/PD-L1 pathway of peripheral T and NK cells and Th2 immune predominance jointly promoted EBV replication and the development of CAEBV. PD-1 blockade therapy reduced the PD-1 expression level of lymphocytes and helped normalize the distribution of the T subsets.

Case Report: HAVCR2 mutation-associated Hemophagocytic lymphohistiocytosis.

Germline HAVCR2 mutation has been reported to be associated with subcutaneous panniculitis-like T-cell lymphoma (SPTCL) leading to Hemophagocytic lymphohistiocytosis (HLH). Several studies have indicated that HAVCR2 mutation can cause HLH even in the absence of lymphoma, though the exact mechanism remains unclear. In this article, we reported five cases of HAVCR2 mutation-associated HLH. Our analysis revealed an elevated level of IL-1RA in the serum of these patients. Furthermore, we investigated the potential mechanisms underlying HLH associated with HAVCR2 mutation based on changes in cytokine levels. Our findings suggest that HAVCR2 mutation may represent a distinct genetic defect underlying HLH, differing from traditional primary HLH.

Pixel level spatial variability modeling using SHAP reveals the relative importance of factors influencing LST.

As an important indicator of the regional thermal environment, land surface temperature (LST) is closely related to community health and regional sustainability in general, and is influenced by multiple factors. Previous studies have paid scant attention to spatial heterogeneity in the relative contribution of factors underlying LST. In this study of Zhejiang Province, we investigated the key factors affecting daytime and nighttime annual mean LST and the spatial distribution of their respective contributions. The eXtreme Gradient Boosting tree (XGBoost) and Shapley Additive exPlanations algorithm (SHAP) approach were used in combination with three sampling strategies (Province-Urban Agglomeration -Gradients within Urban Agglomeration) to detect spatial variation. The results reveal heterogenous LST spatial distribution with lower LST in the southwestern mountainous region and higher temperatures in the urban center. Spatially explicit SHAP maps indicate that latitude and longitude (geographical locations) are the most important factors at the provincial level. In urban agglomerations, factors associated with elevation and nightlight are shown to positively impact daytime LST in lower altitude regions. In the urban centers, EVI and MNDWI are the most notable influencing factors on LST at night. Under different sampling strategies, EVI, MNDWI, NL, and NDBI affect LST more prominently at smaller spatial scales as compared to AOD, latitude and TOP. The SHAP method proposed in this paper offers a useful means for management authorities in addressing LST in a warming climate.

Forward volume scattering function (0.03°-60°) measured using an oblique-incidence particle sizer.

The forward volume scattering function (VSF) is an inherent optical property important in ocean lidar and underwater imaging and communication. The scattered power within 60° contains >90% of total scattered power, making it essential for determining the asymmetry parameter g. Thus, the new oblique-incidence-design Bettersize BT-3000 particle sizer was utilized to measure forward VSF (0.03°-60°) synchronously. A double-exponential model was then used to construct the full-angle-range VSF (0°-180°). The g value calculated therefrom had an uncertainty of <1%. Calibration was implemented using 11-µm beads alone, and the BT-3000's performance was validated.

Potency of the pandemic on air quality: An urban resilience perspective.

Since the outbreak of COVID-19 pandemic, the lockdown policy across the globe has brought improved air quality while fighting against the coronavirus. After the closure, urban air quality was subject to emission reduction of air pollutants and rebounded to the previous level after the potency period of recession. Different response patterns exhibit divergent sensitivities of urban resilience in regard to air pollution. In this paper, we investigate the post-lockdown AQI values of 314 major cities in China to analyse their differential effects on the influence factors of urban resilience. The major findings of this paper include: 1) Cities exhibit considerable range of resilience with their AQI values which are dropped by 21.1% per day, took 3.97 days on average to reach the significantly decreased trough point, and reduced by 49.3% after the lockdown initiatives. 2) Mega cities and cities that locate as the focal points of transportation for nearby provinces, together with those with high AQI values, were more struggling to maintain a good air quality with high rebounds. 3) Urban resilience shows divergent spatial sensitivities to air pollution controls. Failing to consider multi-dimensional factors besides from geomorphological and economical activities could lead to uneven results of environmental policies. The results unveil key drivers of urban air pollution mitigation, and provide valuable insights for prediction of air quality in response to anthropogenic interference events under different macro-economic contexts. Research findings in this paper can be adopted for prevention and management of public health risks from the perspective of urban resilience and environmental management in face of disruptive outbreak events in future.

Study on the Durability of Bamboo Fiber Asphalt Mixture.

To evaluate the durability of bamboo fiber asphalt mixture using four gradation schemes, the durability of the bamboo fiber asphalt mixture is studied considering three aspects: ageing durability, freeze-thaw cycle durability and fatigue durability through the Marshall test, indoor ageing test, uniaxial compression test, low-temperature bending test, immersion Marshall test, freeze-thaw splitting test and four-point bending fatigue test. Nonfiber asphalt mixture and lignin fiber asphalt mixture were used as control groups. The results show that the addition of plant fiber can effectively improve the durability of asphalt mixture. Bamboo fiber modified asphalt mastic has good ductility and adhesion due to its rough surface and good oil absorption performance. Bamboo fiber asphalt mixture has better and more stable low-temperature ageing durability and moisture ageing durability than lignin fiber asphalt mixture, but its mechanical property is weaker than the latter. The improvement effect of the two fibers on the freeze-thaw cycle durability of asphalt mixture is basically the same. Bamboo fiber can improve the flexibility of the mixture and delay the development of cracks so that the mixture has good fatigue durability. The smaller the void ratio, the thicker the asphalt film, and the denser the structure of the mixture, the better the durability. The durability of the stone mastic asphalt (SMA) gradation mixture is better than that of asphalt concrete (AC) gradation. The material composition and aggregate gradation of plant fiber asphalt mixture have a great influence on its durability. In the future, it is necessary to establish a multiparameter comprehensive evaluation index system among fiber type and properties, mixture gradation and durability so as to realize the directional regulation of the durability of different fiber asphalt mixtures. Bamboo fiber is a reliable substitute for lignin fiber, and further research on improving its surface properties and dispersion uniformity can be carried out in the future.

DAXX inhibits cancer stemness and epithelial-mesenchymal transition in gastric cancer.

BACKGROUND: DAXX is a transcription repressor that has been implicated in several types of cancers, but its role in the development of gastric cancer remains unknown. METHODS: We analysed the expression of DAXX in 83 pairs of gastric cancer samples, including neoplastic and adjacent tissues, and correlated the expression levels with clinical stages. We also investigated the molecular mechanisms by which DAXX downregulation promotes cancer growth using both in vitro and in vivo models. RESULTS: DAXX was downregulated in advanced gastric cancer samples. The expression of DAXX inversely correlates with that of cancer stem cell markers CD44 and Oct4 in gastric cancer lines. DAXX overexpression in gastric cancer cells inhibited migration, invasion and epithelial- mesenchymal transition (EMT). The inhibition of EMT was achieved through the repression of SNAI3, a key inducer of EMT, by recruiting HDAC-1 into the nucleus. Using a xenograft mouse model, we demonstrated that the MKN45 cells formed smaller tumours when DAXX was overexpressed. Wild-type AGS cells were not able to form tumours in nude mice, but in contrast, formed visible tumours when DAXX was silenced in the cells. CONCLUSION: We for the first time demonstrated that DAXX functions as a tumour suppressor in gastric cancer by inhibiting stem cell growth and EMT.

Preparation and Properties of Wood Tar-based Rejuvenated Asphalt.

In order to explore the applicability of the rejuvenated asphalt with wood tar as the main raw material, the orthogonal test was used to determine the optimal ratio of wood tar-based rejuvenator. The physical properties, rheological properties and components of matrix asphalt, aged asphalt, wood tar-based rejuvenated asphalt and commercial RA-102# rejuvenated asphalt were tested and compared. The results show that the optimal ratio of wood tar-based rejuvenator is 15wt% wood tar, 0.3wt% biomass fiber, 5wt% plasticizer, 0.3wt% compatibilizer, and 1wt% stabilizer of the mass of aged asphalt. Wood tar-based rejuvenator can restore the physical properties of the aged asphalt to meet the specification requirements. The synergistic effect of biomass fiber and plasticizer make the wood tar-based rejuvenated asphalt has good resistance to accumulated permanent deformation, but its low-temperature cracking resistance needs to be further improved. During the rejuvenation process of aged asphalt, the colloidal state changes from gel-state to sol-state, characterizing that the viscosity of asphalt decreased and the fluidity increased. Wood tar-based rejuvenator can react with aged asphalt to weaken the vibration strength of carbonyl and sulfoxide groups, so as to realize the recovery of service performance. Wood tar-based rejuvenator has better environmental protection and applicability, which is worthy of further study and promotion.

CLIC4 abrogation promotes epithelial-mesenchymal transition in gastric cancer.

Chloride intracellular channel protein 4 (CLIC4) has been implicated in different types of cancers, but the role of CLIC4 in the development of gastric cancer (GC) remains unknown. We analyzed the expression of CLIC4 in 102 pairs of gastric adenocarcinomas by western blot and real-time PCR. Our data revealed that the expression of CLIC4 is reduced in GC tumor tissues compared with adjacent normal tissues. The expression levels of CLIC4 correlate inversely with the clinical stage of GC. CLIC4 expression is lowest in MKN45 cells, which have the highest tumorigenic potential and express the highest levels of cancer stem cell markers CD44 and OCT4, compared with N87 and AGS cells. Exogenous overexpression of CLIC4 downregulated the expression of CD44 and OCT4, and inhibited migration, invasion and epithelial-mesenchymal transition (EMT). Moreover, anchorage-independent growth of GC cells was decreased and the cells became more sensitive to 5-fluorouracil and etoposide treatment when CLIC4 was overexpressed. The ability of N87 cells to form tumors in nude mice was enhanced when CLIC4 was silenced. We, for the first time, demonstrate that CLIC4 suppresses tumor growth by inhibiting cancer cell stemness and EMT.

The Accumulated Response of Deciduous Liquidambar formosana Hance and Evergreen Cyclobalanopsis glauca Thunb. Seedlings to Simulated Nitrogen Additions.

Nitrogen depositions in the Yangtze River Delta have is thought to shift the coexistence of mixed evergreen and deciduous species. In this study, the seedlings of the dominant evergreen species Cyclobalanopsis glauca Thunb. and the deciduous species Liquidambar formosana Hance from the Yangtze River Delta were chosen to test their responses to simulated N additions using an ecophysiological approach. N was added to the tree canopy at rates of 0 (CK), 25 kg N ha-1 year-1 (N25), and 50 kg N ha-1 year-1 (N50). The leaf N content per mass (N m, by 44.03 and 49.46%) and total leaf chlorophyll content (Chl, by 72.15 and 63.63%) were enhanced for both species, and C. glauca but not L. formosana tended to allocate more N to Chl per leaf area (with a higher slope). The enhanced N availability and Chl promoted the apparent quantum yield (AQY) significantly by 15.38 and 43.90% for L. formosana and C. glauca, respectively. Hydraulically, the increase in sapwood density (ρ) for L. formosana was almost double that of C. glauca. Synchronous improved sapwood specific hydraulic conductivity (K S, by 37.5%) for C. glauca induced a significant reduction in stomatal conductance (g s) (p < 0.05) in the N50 treatments, which is in contrast to the weak varied g s accompanied by a 59.49% increase in K S for L. formosana. As a result, the elevated maximum photosynthesis (A max) of 12.19% for L. formosana in combination with the increase in the total leaf area (indicated by a 37.82% increase in the leaf area ratio-leaf area divided by total aboveground biomass) ultimately yielded a 34.34% enhancement of total biomass. In contrast, the A max and total biomass were weakly promoted for C. glauca. The reason for these distinct responses may be attributed to the lower water potential at 50% of conductivity lost (P 50) for C. glauca, which enables higher hydraulic safety at the cost of a weak increase in Amax due to the stomatal limitation in response to elevated N availability. Altogether, our results indicate that the deciduous L. formosana would be more susceptible to elevated N availability even if both species received similar N allocation.

Spatiotemporal Variability of Soil Nitrogen in Relation to Environmental Factors in a Low Hilly Region of Southeastern China.

Soil total nitrogen (TN) plays a major role in agriculture, geochemical cycles and terrestrial ecosystem functions. Knowledge regarding the TN distribution is crucial for the sustainable use of soil resources. This paper therefore aims to characterize the spatiotemporal distribution of soil TN and improve the current understanding of how various factors influence changes in TN. Natural characteristics and remote sensing (RS) variables were used in conjunction with the random forest (RF) model to map the TN distribution in a low hilly region of southeastern China in 1979, 2004 and 2014. The means and changes of TN in different geographic regions and farmland protection regions were also analyzed. The results showed that: (1) the TN showed an increasing trend in the early periods and exhibited a decreasing trend from 2004 to 2014; (2) the geographic and RS variables played more important roles in predicting TN distribution than did the other variables; and (3) changes in the fertilization and crop planting structure caused by soil testing and formulated fertilization techniques (STFFT-Soil Testing and Formulated Fertilization Techniques) as well as farmland protection policies influenced the spatiotemporal variability of TN. Evidently, more attention should be focused on improving the quality and soil fertility in the surrounding low mountainous areas.

Runx1 promotes satellite cell proliferation during ischemia - Induced muscle regeneration.

RUNX1 is a transcription factor that is not expressed in uninjured muscles, but can be detected in denervated muscles, suggesting a role of RUNX1 in muscle's response to injury. However, the role of RUNX1 in muscle's response to ischemia has not been reported. Our study showed that Runx1 is up regulated in skeletal muscle during ischemia reperfusion induced injury. Over-expression of Runx1 in C2C12 cells inhibits myogenic differentiation, but promotes proliferation of myoblasts. Consistent with these findings, we found that Runx1 expression was decreased in differentiated satellite cells. Our results indicate that Runx1 regulates muscle regeneration by promoting proliferation of satellite cells.

Angiotensin-II-induced Muscle Wasting is Mediated by 25-Hydroxycholesterol via GSK3ß Signaling Pathway.

While angiotensin II (ang II) has been implicated in the pathogenesis of cardiac cachexia (CC), the molecules that mediate ang II's wasting effect have not been identified. It is known TNF-α level is increased in patients with CC, and TNF-α release is triggered by ang II. We therefore hypothesized that ang II induced muscle wasting is mediated by TNF-α. Ang II infusion led to skeletal muscle wasting in wild type (WT) but not in TNF alpha type 1 receptor knockout (TNFR1KO) mice, suggesting that ang II induced muscle loss is mediated by TNF-α through its type 1 receptor. Microarray analysis identified cholesterol 25-hydroxylase (Ch25h) as the down stream target of TNF-α. Intraperitoneal injection of 25-hydroxycholesterol (25-OHC), the product of Ch25h, resulted in muscle loss in C57BL/6 mice, accompanied by increased expression of atrogin-1, MuRF1 and suppression of IGF-1/Akt signaling pathway. The identification of 25-OHC as an inducer of muscle wasting has implications for the development of specific treatment strategies in preventing muscle loss.

Identification of specific biomarkers for gastric adenocarcinoma by ITRAQ proteomic approach.

The aim of this study was to identify biomarkers for gastric cancer (GC) by iTRAQ. Using proteins extracted from a panel of 4 pairs of gastric adenocarcinoma samples (stage III-IV, Her-2 negative), we identified 10 up regulated and 9 down regulated proteins in all four pairs of GC samples compared to adjacent normal gastric tissue. The up regulated proteins are mainly involved in cell motility, while the down regulated proteins are mitochondrial enzymes involved in energy metabolism. The expression of three up regulated proteins (ANXA1, NNMT, fibulin-5) and one of the down regulated proteins (UQCRC1) was validated by Western Blot in 97 GC samples. ANXA1 was up regulated in 61.36% of stage I/II GC samples compared to matched adjacent normal gastric tissue, and its expression increased further in stage III/IV samples. Knockdown of ANXA1 by siRNA significantly inhibited GC cell migration and invasion, whereas over expression of ANXA1 promoted migration and invasion. We found decreased expression of UQCRC1 in all stages of GC samples. Our data suggest that increased cell motility and decreased mitochondrial energy metabolism are important hallmarks during the development of GC.