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Lin Chen,1,2,5 Hongyun Huang,3 Haitao Xi,4,5 Gengsheng Mao3 1Medical Center, Tsinghua University, 2Tsinghua University Yuquan Hospital, 3General Hospital of Chinese People's Armed Police Forces, 4Beijing Rehabilitation Hospital of Capital Medical University, 5Beijing Hongtianji Neuroscience Academy, Beijing, People’s Republic of China Abstract: Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disease characterized by progressive paralysis and motor neuron death. In addition to symptomatic managements such as ventilation and nutritional support, neurorestorative therapies have demonstrated anti-neurodegenerative potential and may improve quality of life for patients. Currently, clinical neurorestorative strategies include pharmacological management (granulocyte colony stimulating factor), neuromodulatory intervention (repetitive transcranial magnetic and cortical stimulation), cell transplantation (bone marrow stromal cells, olfactory ensheathing cells, granulocyte colony stimulating factor-mobilized peripheral blood stromal cells, hematopoietic stem and progenitor cells, neural stem/progenitor cells, CD133+ cells and CD34+ cells), bioengineering and tissue engineering therapy, and combined neurorehabilitative treatment. In this review, we describe the latest progress in clinical neurorestorative management of amyotrophic lateral sclerosis and discuss the underlying evidence base. Keywords: amyotrophic lateral sclerosis, neurorestorative treatment, cell transplantation, clinical trial

The space nuclear reactor cooled by heat pipes has become the preferred choice for future space missions and deep space exploration missions. The use of low-enriched uranium (LEU) is promoted to achieve the goal of nuclear non-proliferation worldwide. In this study, a lithium heat pipe cooled space reactor with LEU (HP-LEU) was proposed based on Heat Pipes-Segmented Thermoelectric Module Converters (HP-STMCs), with the addition of moderators. The HP-LEU employs yttrium hydride (YH2) as the moderator and 19.9 % enriched uranium nitride (UN) as the fuel. The neutronics analysis has been performed on the HP-LEU reactor and the results have showed that the HP-LEU has a lifetime of more than 12 years. Two control systems have been applied in the reactor and have demonstrated the capacity to independently regulate and shut down the reactor. The total temperature reactivity coefficients are consistently negative, indicating that the HP-LEU reactor is inherently safe during operation. During normal operation, the temperatures of the materials are all acceptable. This study can serve as a reference for lithium heat pipe cooled space reactors with LEU.

ABSTRACT: Objectives: ZR-202-CoV and ZR-202a-CoV are novel recombinant vaccines containing 25 µg of the prototype (Wuhan strain) or B.1.351 strain (Beta variant) SARS-CoV-2 S-protein expressed in CHO cells, respectively, adjuvanted with Al(OH)3 and CpG-ODN. We assessed their safety and immunogenicity in this Phase I, randomized, observer-blind, controlled study in Mali. Design: Sixty healthy 18–55-year-old adults randomized 1:1:1 received two doses of ZR-202-CoV, ZR-202a-CoV, or ComirnatyⓇ 28 days apart. Primary outcome measures were solicited and unsolicited adverse events (AEs) including AESI (Adverse Events of Special Interest); secondary outcome was immunogenicity measured as SARS-CoV-2 specific neutralizing antibodies. Participants were followed up for 1 year. Results: Injection site pain and headache were the most frequent solicited local and systemic AEs, respectively. No unsolicited AEs or SAEs related to vaccination were reported during the study period. Although most participants had detectable neutralizing antibodies at baseline robust immune responses were observed in all vaccine groups after the first dose with no further increase after the second dose. Cross-neutralizing antibody responses against Beta, Delta, and Omicron BA.5 variants were similar in magnitude after ZR-202-CoV, ZR-202a-CoV and ComirnatyⓇ. Conclusions: Similar reactogenicity and immunogenicity profiles of ZR-202-CoV, ZR-202a-CoV and ComirnatyⓇ support further clinical investigation in a wider population.

Background: Barium, as a heavy divalent alkaline earth metal, can be found in various products such as rodenticides, insecticides, depilatories, and fireworks. Barium can be highly toxic upon both acute and chronic exposure. The toxicity of barium compounds is dependent on their solubility. Both suicidal and accidental exposures to soluble barium can cause toxicity. Case summary: We report a case characterized by two different wide QRS complex tachycardia in a patient with acute barium poisoning, one due to barium-induced ventricular tachycardia (VT) under hypokalemia and, subsequently, sino-ventricular conduction with intraventricular conduction delay due to hyperkalemia after aggressive potassium supplementation. The latter may be misdiagnosed as VT for the history of acute barium poisoning and the absence of peaked T wave in hyperkalemia. Of note, another hemodynamically unstable VT and profound hypokalemia occurred during the potassium-lowering therapy, which, in addition to barium poisoning, may also be due to the iatrogenic hypokalemia. We also observed the prominent T-U waves at serum potassium of 4.6 mM 12 hours after admission, which may indicate that barium had not been completely cleared from the plasma at that moment. There are some parallels to the Andersen-Tawil syndrome with prominent T-U waves and risk of ventricular tachycardias. To our knowledge, this is the first case report of conversion from hypokalemia to hyperkalemia, and in a short moment, from hyperkalemia to hypokalemia, in acute barium poisoning. Conclusion: In addition to profound hypokalemia secondary to acute barium poisoning, hyperkalemia may also occur after aggressive potassium supplementation. A more careful rather than too aggressive potassium supplementation may be suitable in these cases of hypokalemia due to an intracellular shift of potassium. And a iatrogenic hypokalemia risk in the treatment of rebound hyperkalemia in barium poisoning must be considered.

Efficient translation mediated by the 5′ untranslated region (5′ UTR) is essential for the robust efficacy of mRNA vaccines. However, the N1-methyl-pseudouridine (m1Ψ) modification of mRNA can impact the translation efficiency of the 5′ UTR. We discovered that the optimal 5′ UTR for m1Ψ-modified mRNA (m1Ψ–5′ UTR) differs significantly from its unmodified counterpart, highlighting the need for a specialized tool for designing m1Ψ–5′ UTRs rather than directly utilizing high-expression endogenous gene 5′ UTRs. In response, we developed a novel machine learning-based tool, Smart5UTR, which employs a deep generative model to identify superior m1Ψ–5′ UTRs in silico. The tailored loss function and network architecture enable Smart5UTR to overcome limitations inherent in existing models. As a result, Smart5UTR can successfully design superior 5′ UTRs, greatly benefiting mRNA vaccine development. Notably, Smart5UTR-designed superior 5′ UTRs significantly enhanced antibody titers induced by COVID-19 mRNA vaccines against the Delta and Omicron variants of SARS-CoV-2, surpassing the performance of vaccines using high-expression endogenous gene 5′ UTRs.

Accompanied by the accelerated growth rate of chickens, the quality of chicken meat has deteriorated in recent years. Wooden breast (WB) is a severe myopathy affecting meat quality, and its pathophysiology depends on gene expression and intercellular interactions of various cell types, which are not yet fully understood. We have performed a comprehensive transcriptomic and metabolomic atlas of chicken WB muscle. Our data showed a significant increase in the number of immune cells, WB muscle displayed a unique cluster of macrophages (cluster 11), distinct from the M1 and M2 macrophages. Regarding the myocytes, the most significant differences were the decrease in cell number and the intensification of fatty deposits. Satellite cells were involved in muscle repair and regeneration producing more collagen. Interestingly, the interaction network in the WB group was weaker compared to that in normal breast muscle. Additionally, we found six key differential metabolites across 22 pathways. When WB occurs, myocytes and endothelial cells undergo apoptosis, macrophages are activated and exert immune functions, satellite cells participate in muscle rebuilding and repair, and the content of metabolites undergoes significant changes. This cell transcriptome profile provides an essential reference for future studies on the development and remodeling of WB.

Groundwater pollution resulting from leachate leakage at landfill sites has garnered significant attention. Investigating the migration of pollutants from these landfills to adjacent groundwater is crucial for understanding the diffusion patterns and extent of contamination. It is imperative to develop cost-effective yet highly efficient tracer techniques to aid landfill operators in monitoring groundwater contamination stemming from their operations. The primary objective of this research was to compare the roles of conservative tracers sodium (Na+) and chloride (Cl−), and conventional pollutants permanganate oxidation (CODMn), ammonium nitrogen (NH4+-N), lead (Pb), and zinc (Zn) in assessing pollution levels from municipal solid waste landfills to groundwater. For this purpose, a typical municipal solid landfill was selected to investigate the origin of Cl−, groundwater quality, and spatiotemporal variations of multiple contaminations. Geochemistry analyses revealed that Na–Cl and Ca–HCO3 were the dominant groundwater type in this study and landfill was the primary source of Cl− in groundwater, with an average contribution of 78 %. Groundwater in proximity to the landfill (5#, 2#, 22#, 23#) exhibited elevated concentrations of Na+ (15.6–914.0 mg/L), Cl− (8.9–1352.0 mg/L), CODMn (0.54–95.9 mg/L), and NH4+-N (0.33–49.0 mg/L), yet demonstrated reduced levels of Pb (0.2–391.0 μg/L) and Zn (2.0–112.8 μg/L). In contrast, groundwater located at a considerable distance from the landfill (13#, 18#, 15#, 26#) displayed the inverse trend, with relatively low concentration of Na+ (3.2–8.5 mg/L), Cl− (0.1–0.7 mg/L), CODMn (0.28–4.78 mg/L), and NH4+-N (0.03–0.52 mg/L), but increased levels of Pb (1.2–483.0 μg/L) and Zn (1.6–357.0 μg/L). The primary determinant of groundwater quality near the landfill was NH4+-N, with the highest pollution index (Pi) of 492.85, whereas Pb was the predominant factor affecting water quality in areas distant from the landfill, with the highest pollution index (Pi) of 10.9. While no discernible seasonal variation was detected for all pollutants, spatial variation can be observed that pollution levels decreased progressively with increasing distance from the landfill, a trend particularly corroborated by the conservative Cl− and Na+ measurements. This research suggests that conservative ions, such as Cl− and Na+, exhibit superior efficacy in tracing the pollution range from municipal solid landfills to groundwater. Therefore, monitoring these conservative ions in groundwater can yield a more precise understanding of the extent of groundwater contamination originated from landfills.

Accurate and non-destructive estimation of leaf chlorophyll content (LCC) is crucial for optimizing cotton production. This study enhances the SCOPE model by integrating unmanned aerial vehicle (UAV)-derived multispectral data with leaf area index (LAI) from LiDAR data, significantly improving precision of LCC estimation, particularly during crucial growth stages of cotton. We construct and analyze three cost functions: COST1, which relies solely on spectral data; COST2, which incorporates direct LAI inputs; and COST3, which adjusts for LAI measurement uncertainties by combining spectral term with an error term representing the squared relative error between measured and model-estimated LAI. Our findings indicate that while COST1 establishes a baseline, COST2 and COST3 provide more accurate LCC estimations. COST3, validated against theoretical data, field-measured cotton datasets, and an additional maize dataset, proves most robust, maintaining consistent accuracy across all growth stages especially when considering input data uncertainties. This highlights the importance of integrating appropriate forms of LAI in cost functions to refine LCC estimation. Future research should focus on improving data acquisition quality and developing more advanced cost functions to advance LCC estimation further.

The frequent occurrence of urban floods (UFs) poses significant threats to citizens’ lives and the national economy. Utilizing machine learning to assess urban flood susceptibility (UFS) provides valuable decision support for UF management. However, the precision of current studies is usually influenced by the variability of temporal factors like extreme rainfall, which limits the accurate identification of urban flood-susceptible regions (UFSRs). To address this issue, we present a novel approach that leverages the spatiotemporal distribution and characteristics of UFS to accurately identify UFSRs. In our case study of the Greater Bay Area (GBA) in China, we employed the Random Forest to assess the spatiotemporal distribution of UFS. We then used the Savitzky-Golay filter to correct UFS data based on the UFS time series from 2011 to 2020. The Theil-Sen median slope, Mann-Kendall test, and Hurst analysis were used to explore the spatiotemporal patterns of UFS. Shapley additive explanation was applied to quantify the contribution of selected variables. Our findings include: (1) UFS in the GBA demonstrates a rising trend, with high susceptibility areas increasing from 6.3 % in 2011 to 7.4 % in 2020; (2) UFSRs, covering approximately 11 % of the GBA, are primarily concentrated in the cities located around the central GBA; and (3) human behavior factors have a more significant influence on UF than natural ones. We believe the presented framework for the accurate extraction of UFSRs provides valuable decision support for sustainable city development.

Tibetan sheep play a vital role in the livelihoods of herders and are an important part of the ecosystem of the Tibetan Plateau. In order to study the characteristics of the gut microorganisms of Tibetan sheep at high altitude, this study employed macrogenomic techniques to analyse the diversity and differences in the gut flora of Tibetan sheep in different regions of high altitude and high cold. The results demonstrated that at the phylum level, the dominant phylum in the ileo-cecum segment of Tibetan sheep in Qilian, Henan and Gonghe counties was identical, namely Euryarchaeota, Firmicutes and Ascomycota. At the level of the archaebacterial genus, the dominant bacteria of the ileocecal segment of Tibetan sheep in Qilian County, Henan County and Gonghe County were Methanobrevibacter. At the level of bacterial genus, the dominant bacteria of Tibetan sheep ileocecal in Qilian County and Henan County were Bacteroides, while in Gonghe County, the dominant bacteria were Bifidobacterium. At the level of fungal genus, there were notable differences in the abundance of Tibetan sheep ileocecal genus across different regions. However, the abundance of cecum genus exhibited a more consistent trend across regions. From the perspective of functional prediction, the metabolic pathways enriched in the intestinal segments of Tibetan sheep in different regions were found to be identical, with the relative abundance of each functional gene also being essentially uniform. This result will provide a foundation for further research on the mechanism of action of gut microbes in ruminants at high altitude and alpine regions.

This study aims to investigate the influence of different fiber types, lengths, and contents on their performance in freeze-thaw environments. Indoor freeze-thaw tests were conducted to evaluate the flexural strength, compressive strength, and mass loss of fiber-reinforced geopolymer materials. Additionally, SEM and XRD analyses were performed to examine the internal structure of the geopolymer composites. The results demonstrated that the incorporation of different fibers significantly improved various properties, particularly the flexural strength of the specimens. With an increasing number of freeze-thaw cycles, surface cracks became more prominent in the geopolymer specimens, leading to a gradual decrease in frost resistance. However, the addition of an appropriate amount of fiber effectively enhanced frost resistance. Following freeze-thaw exposure, an increase in fiber content initially resulted in a decrease and subsequently an increase in relative flexural strength, compressive strength, and mass loss. Notably, studies revealed that polypropylene fibers with a length of 9 mm and a content of 0.9 % exhibited minimal mass and strength loss. SEM analysis indicated uniform distribution of fibers within the geopolymer matrix, contributing to improved flexural strength and enhanced frost resistance in fiber-reinforced structures. XRD results indicate that red mud-slag based geopolymers produce high-strength hydrated calcium (aluminosilicate) silicate and hematite phases, which enhances the mechanical properties and durability of the specimens. In conclusion, this study highlights that incorporating suitable fibers can enhance the durability and performance of red mud-slag based geopolymers under freeze-thaw conditions. The findings provide valuable insights for optimizing fiber type, length, and content to achieve superior mechanical properties and frost resistance in geopolymer composites.

Electrospun nanofibers have been widely employed in bone tissue engineering for their ability to mimic the micro to nanometer scale network of the native bone extracellular matrix. However, the dense fibrous structure and limited mechanical support of these nanofibers pose challenges for the treatment of critical size bone defects. In this study, we propose a facile approach for creating a three-dimensional scaffold using interconnected electrospun nanofibers containing melatonin (Scaffold@MT). The hypothesis posited that the sponge-like Scaffold@MT could potentially enhance bone regeneration and angiogenesis by modulating mitochondrial energy metabolism. Melatonin-loaded gelatin and poly-lactic-acid nanofibers were fabricated using electrospinning, then fragmented into shorter fibers. The sponge-like Scaffold@MT was created through a process involving homogenization, low-temperature lyophilization, and chemical cross-linking, while maintaining the microstructure of the continuous nanofibers. The incorporation of short nanofibers led to a low release of melatonin and increased Young's modulus of the scaffold. Scaffold@MT demonstrated positive biocompatibility by promoting a 14.2 % increase in cell proliferation. In comparison to the control group, Scaffold@MT significantly enhanced matrix mineralization by 3.2-fold and upregulated the gene expression of osteoblast-specific markers, thereby facilitating osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs). Significantly, Scaffold@MT led to a marked enhancement in the mitochondrial energy function of BMMSCs, evidenced by elevated adenosine triphosphate (ATP) production, mitochondrial membrane potential, and protein expression of respiratory chain factors. Furthermore, Scaffold@MT promoted the migration of human umbilical vein endothelial cells (HUVECs) and increased tube formation by 1.3 times compared to the control group, accompanied by an increase in vascular endothelial growth factor (VEGFA) expression. The results of in vivo experiments indicate that the implantation of Scaffold@MT significantly improved vascularized bone regeneration in a distal femur defect in rats. Micro-computed tomography analysis conducted 8 weeks post-surgery revealed that Scaffold@MT led to optimal development of new bone microarchitecture. Histological and immunohistochemical analyses demonstrated that Scaffold@MT facilitated bone matrix deposition and new blood vessel formation at the defect site. Overall, the utilization of melatonin-loaded nanofiber sponges exhibits significant promise as a scaffold that promotes bone growth and angiogenesis, making it a viable option for the repair of critical-sized bone defects.

Objective: The study aims to investigate the causal relationship between cheese intake and caries occurrence by a two-sample Mendelian randomization method (TSMR). Methods: Data from a genome-wide association study (GWAS) on cheese intake as an exposure factor were collected, and dental caries was the outcome variable, appropriate SNPs were selected as instrumental variables (IVs). The TSMR was analyzed by the inverse variance weighting (IVW) method, weighted median method, MR-Egger regression method, simple model and weighted model. Results: We identified forty-four single-nucleotide polymorphisms (SNPs) in the gene encoding group-specific component (cheese) that were associated with cheese intake, and IVW was adopted. The IVW method supported a relationship between cheese intake and the risk of dental caries occurrence[OR,1.00(95 %CI,0.99–1.00), P = 0.039

In high-intensity farming, swiftly and accurately adjusting the proportion of artificially reared pollinators according to the flowering phenology of crops is vital. This adjustment is essential for sustaining crop yields without disrupting the ecological niche of native pollinators. Although advancements in remote sensing provide practical means to gather data on crop coverage and extent, identifying insect-pollinated crops during their initial flowering to guide the deployment of managed pollinators is an underexamined research area. Here, we tested the capability of utilizing Sentinel-2 satellite images combined with a deep learning model to map crop fields during the initial flowering stage of insect-pollinated crops in Zhaosu County, Xinjiang, China. Specifically, we examined rapeseed fields by employing 12 neural network designs to identify images of the initial flowering stage. Different network combinations of three convolutional neural network (CNN) models (U-Net, PSPNet, and DeepLab V3) and four different backbone networks (ResNet-18, ResNet-34, ResNet-50, and ResNet-101) were explored to determine the most effective model for detecting rapeseed fields at the initial flowering stage. A comparison was conducted with Sentinel-2 images obtained at the peak stage of rapeseed flowering. Our results suggest that the use of a deep learning model in combination with Sentinel-2 image data can successfully identify rapeseed fields at the initial flowering stage, thereby offering preliminary insights for the strategic introduction of managed pollinators. The PSPNet model emerged as the superior choice for the identification of rapeseed fields, exhibiting high accuracy in both detection and boundary recognition, with F1 scores of 88.17 % and an intersection over union (IoU) of 53.11 % during initial flowering and F1 scores of 93.33 % with an IoU of 53.49 % during peak flowering. The planting area of rapeseed fields detected by the model in Zhaosu County was 122.16 km2, distributed within an area of 1068 km2. These findings can provide foundational data for informed decisions regarding artificial pollinator supplementation, helping to sustain the health and stability of agricultural ecosystems.

Summary: Mounting evidence supports the role of neuroinflammation in radiation-induced brain injury (RIBI), a chronic disease characterized by delayed and progressive neurological impairment. Asparagine endopeptidase (AEP), also known as legumain (LGMN), participates in multiple malignancies and neurodegenerative diseases and may potentially be involved in RIBI. Here, we found AEP expression was substantially elevated in the cortex and hippocampus of wild-type (Lgmn+/+) mice following whole-brain irradiation. Lgmn knockout (Lgmn−/−) alleviated neurological impairment caused by whole-brain irradiation by suppressing neuronal senescence. Bulk RNA and metabolomic sequencing revealed AEP’s involvement in the antigen processing and presentation pathway and neuroinflammation. This was further confirmed by co-culturing Lgmn+/+ primary neurons with the conditioned media derived from irradiated Lgmn+/+ or Lgmn−/− primary microglia. Furthermore, esomeprazole inhibited the enzymatic activity of AEP and RIBI. These findings identified AEP as a critical factor of neuroinflammation in RIBI, highlighting the prospect of targeting AEP as a therapeutic approach.

Human adenovirus (HAdV) infection is a major cause of respiratory disease, yet no antiviral drugs have been approved for its treatment. Herein, we evaluated the antiviral and anti-inflammatory effects of cyclin-dependent protein kinase (CDK) inhibitor indirubin-3′-monoxime (IM) against HAdV infection in cells and a transgenic mouse model. After evaluating its cytotoxicity, cytopathic effect reduction, antiviral replication kinetics, and viral yield reduction assays were performed to assess the anti-HAdV activity of IM. Quantitative real-time polymerase chain reaction (qPCR), quantitative reverse transcription PCR (qRT-PCR), and western blotting were used to assess the effects of IM on HAdV DNA replication, transcription, and protein expression, respectively. IM significantly inhibited HAdV DNA replication as well as E1A and Hexon transcription, in addition to significantly suppressing the phosphorylation of the RNA polymerase II C-terminal domain (CTD). IM mitigated body weight loss, reduced viral burden, and lung injury, decreasing cytokine and chemokine secretion to a greater extent than cidofovir. Altogether, IM inhibits HAdV replication by downregulating CTD phosphorylation to suppress viral infection and corresponding innate immune reactions as a promising therapeutic agent.

Quantifying the evapotranspiration (ET) water consumption characteristics of typical vegetation [Robinia pseudoacacia (single vegetation), mixed plantations of Robinia pseudoacacia and Platycladus orientalis (double-mixed vegetation), and natural grassland (multiple-mixed vegetation)] in the Chinese Loess Plateau has both theoretical and practical significance. However, the proportionality and inverse hypotheses of ET, namely, the FAO-56 method and generalized complementary relationship (GCR), have limitations when used individually to estimate ET, evaporation (E), and transpiration (T). This study explores the feasibility of scaling water stress coefficient (Ks) using calibration-free or parameterized GCR for different vegetation types and quantities. The single crop coefficient (Kc) curves and basal crop coefficient adjustment (Kcb-a/Kcb-p) curves of typical vegetation were defined and validated to partition ET without soil moisture usage. The results revealed that both curves exhibited polynomial functional response relationships to the week ordinal (WO) of the growing season within a complete hydrological cycle (with 0.60 < R2 < 0.78 at the 0.01 significance level). By expressing the soil evaporation coefficient (Ke) as a function of Ks, Kc, and Kcb, the calibration-free combined method (combining the GCR and the FAO-56 method – GCR/FAO-56) demonstrated superior simulation performance for E, T, and ET across different vegetation types with an average Nash–Sutcliff Efficiency of 0.71 during the validation period compared to that of the parameterized method, with the highest sensitivity in E simulation. The simulated E, T, and ET values closely matched the actual values and maintained the order of Robinia pseudoacacia > mixed plantation > natural grassland during the growing season. The average biases for E, T, and ET during the validation period were 18.5, 7.0, and 25.5 mm, respectively, in Robinia pseudoacacia; 10.8, 11.1, and 19.7 mm in mixed plantation; and 2.7, 7.0, and 19.6 mm in natural grassland. The overall T/ET ratios for both plantations exceeded 51.07%, with mixed plantation being higher, surpassing 70% in dry years and exhibiting minimal variation in T (44.4 mm) across hydrological years. However, T/ET ratios in natural grassland were < 0.5, indicating that E was the primary form of water consumption. Average relative biases of the simulated and actual T/ET values were only 1.76%, 2.53%, and 1.87% for Robinia pseudoacacia, mixed plantation, and natural grassland, respectively. Furthermore, the accuracy of the calibration-free combined method increased with the number of vegetation species during the validation period. This study extended and discussed the feasibility in typical vegetation of combining the positive and negative correlation principles of evapotranspiration and further provided a possibility for how to partition ET with a fewer dataset [Rn, u, Tavg, RH or Td, P, LAI] without soil moisture, and also provided scientific suggestions for future vegetation restoration as well as water resources management.

The repair of critical-sized bone defects poses a significant challenge due to the absence of periosteum, which plays a crucial role in coordinating the processes of osteogenesis and vascularization during bone healing. Herein, we hypothesized that melatonin-encapsuled silk Fibronin electrospun nanofibers (SF@MT) could provide intrinsic induction of both osteogenesis and angiogenesis, thereby promoting vascularized bone regeneration. The sustained release of melatonin from the SF@MT nanofibers resulted in favorable biocompatibility and superior osteogenic induction of bone marrow mesenchymal stem cells (BMMSCs). Interestingly, melatonin promoted the migration and tube formation of human umbilical vein endothelial cells (HUVECs) in a BMMSC-dependent manner, potentially through the upregulation of vascular endothelial growth factor (VEGFA) expression in SF@MT-cultured BMMSCs. SF@MT nanofibers enhanced the BMMSC-mediated angiogenesis by activating the PI3K/Akt signaling pathway. In vivo experiments indicated that the implantation of SF@MT nanofibers into rat critical-sized calvarial defects significantly enhances the production of bone matrix and the development of new blood vessels, leading to an accelerated process of vascularized bone regeneration. Consequently, the utilization of melatonin-encapsulated silk Fibronin electrospun nanofibers shows great promise as a potential solution for artificial periosteum, with the potential to regulate the coupling of osteogenesis and angiogenesis in critical-sized bone defect repair.

Urban Flood (UF) and Urban Heat Island (UHI) become prevalent “urban diseases” currently. Previous studies usually regarded UF and UHI as separate issues that requires respective concentration; however, UF and UHI are inextricably connected so that they should be considered together. Hence, this paper proposes a spatiotemporal framework to link UF and UHI by developing an Urban Flood Heat Island (UFHI) index, taking the Greater Bay Area (GBA) in China as the study case. Random Forest (RF) classifier and Urban-Rural Dichotomy were selected to compute the spatiotemporal distribution of UF susceptibility (UFS) and UHI intensity (UHII), respectively. Theil-Sen Median Slope, Mann-Kendall Test, and Hurst analysis were used to explore the spatiotemporal variation pattern of the UF-UHI joint risk. Spatial Durbin Model was used to compute the correlation between UFS and UHII. RF regressor was employed to quantify the contribution of the common driving factors. We found: (1) UFS and UHII are spatiotemporally correlated, thus UHII can be used as a control variable for the refined UFS assessments, (2) the areas with the UF-UHI joint risk of persistently significant increase (∼7.9 %) majorly distributed in the central region, (3) according to the contributions of factors, UF and UHI in the GBA could be effectively alleviated by breaking the continuous impervious surfaces by introducing blue-green structures. This study offers a new perspective for the effective alleviation of UF and UHI, which would be helpful for the sustainable development of cities in developing countries where human and material sources are limited.

In this study, the Sn58Bi-xMg (x = 0, 0.2, 0.4, 0.6, 0.8, 1.0) composite solders were synthesized to explore the impact of Mg particles. The study examined the wettability, thermal properties, mechanical properties, microstructure, and growth of interfacial IMC (intermetallic compound) of composite solder. Experimental results showed that adding Mg particles had no significant impact on the melting point of Sn58Bi solder. However, increasing the Mg content increased the undercooling of the solder. Moreover, the incorporation of Mg particles resulted in a consistent rise in the coefficient of thermal expansion (CTE) of the composite solder, ranging from 11.4 × 10−6/°C to 15.6 × 10−6/°C. It was worth noting that including Mg particles enhanced the wetting ability of Sn58Bi alloy on Cu substrates. With a 0.4 % addition of Mg particles, the wetting area could be increased by 60.14 %, and the lowest wetting angle was approximately 10.43°. Adding Mg particles resulted in an amelioration in the brittleness of the Bi-rich phase within the solder matrix, coupled with a decrease in both the thickness of IMC and the grain size at the joint interface. Compared to the joints without mixed Mg particles, the shear strength of Sn58Bi-0.4Mg solder joints and the microhardness of the alloy increased by 30 % and decreased by 10 %, respectively. Also, the presence of dimples within the fracture indicated a rise in the ductility of the solder joints. Overall, adding 0.4 wt% Mg particles in this experiment resulted in a more effective modification of the Sn58Bi solder comprehensive properties.

There are currently approximately 4000 mutations in the SARS-CoV-2 S protein gene and emerging SARS-CoV-2 variants continue to spread rapidly worldwide. Universal vaccines with high efficacy and safety urgently need to be developed to prevent SARS-CoV-2 variants pandemic. Here, we described a novel self-assembling universal mRNA vaccine containing a heterologous receptor-binding domain (HRBD)-based dodecamer (HRBDdodecamer) against SARS-CoV-2 variants, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (B.1.1.28.1), Delta (B.1.617.2) and Omicron (B.1.1.529). HRBD containing four heterologous RBD (Delta, Beta, Gamma, and Wild-type) can form a stable dodecameric conformation under T4 trimerization tag (Flodon, FD). The HRBDdodecamer -encoding mRNA was then encapsulated into the newly-constructed LNPs consisting of a novel ionizable lipid (4N4T). The obtained universal mRNA vaccine (4N4T-HRBDdodecamer) presented higher efficiency in mRNA transfection and expression than the approved ALC-0315 LNPs, initiating potent immune protection against the immune escape of SARS-CoV-2 caused by evolutionary mutation. These findings demonstrated the first evidence that structure-based antigen design and mRNA delivery carrier optimization may facilitate the development of effective universal mRNA vaccines to tackle SARS-CoV-2 variants pandemic.

The discharge mode has a great influence on the energy consumption of electric vehicles, especially at cold environment, soak in cold environment will lead to the decrease of the temperature of the vehicle/battery, resulting in the increase of energy consumption. In this paper, a segmented driving energy consumption test method was designed according to the real road discharge low of private vehicle, and the continuous and segmented energy consumption tests were carried out on the laboratory drum under −10 °C. From the perspective of energy flow, the differences of driving energy consumption, air conditioner energy consumption and brake energy recovery under the two test methods are analyzed. Results shown that soak in cold environment will cause the energy consumption of driving and air conditioner to increase by 5.5% and 43.8%, respectively, and also lead to a 17.1% decrease in brake recovery energy.

In order to study the influence of high and low temperature environments on the energy consumption of battery electric vehicles, this paper takes Tianjin as an example to collect the actual road data of 8 battery electric passenger cars for eight months. It determines the correlation between each characteristic parameter and energy consumption based on the maximum mutual information coefficient of short stroke segments, of which the average driving speed correlation is the highest, which is 0.785. Given the two factors that have a greater impact on energy consumption in high and low temperature environments: driving resistance and air conditioning on motion and idle energy consumption analysis, the study shows that in terms of driving resistance, high temperature and low temperature energy consumption are reduced and increased by 5.4% and 13.3% respectively relative to normal temperature; The energy consumption of high temperature and low temperature air conditioner switching on increased by 17.12% and 47.48% respectively compared with the air conditioner off.

Heavy vehicles have higher driving time and NOx emission level under low-load scenarios. Developing and inducting corresponding test cycle into emission valuation and certification standards is an effective method to improve translation from test emission results to real-world emission control benefits. At present, China is short of systematic research and achievements in this field. Present certification cycle failed to evaluate low-load emission. In America, CARB firstly applied least-square method to fit the multi-modal normal distribution with moving window average load, thus defined low-load data set. Secondly, applied K-means clustering method to classify and identity typical low-load driving scenarios. Thirdly, applied model to translate vehicle profile to construct low-load profile library. Finally, selected and combined representative profiles to construct the Low-load test cycle (LLC). Further more, by engine dynamo meter test and model simulation, LLC was used to evaluate the after treatment system and improve emission control technology under low-load scenarios. This paper comprehensively studied the overall process of cycle construction, verification and application, explained in detail the technical details of cycle construction routine, thus, provided practical technical support for development of China’s low-load test cycle.

Multiple system atrophy (MSA) is a rare form of adult-onset α-synucleinopathy. Meige syndrome, identified as bilateral blepharospasm and oromandibular dystonia, is a type of focal dystonic movement disorder. This case report aims to highlight the clinical features of multiple system atrophy associated with Meige syndrome in a patient. Additionally, we aim to provide the treatment experience in a patient with Meige syndrome as this is an extremely rare clinical case.

Microbially derived, protein-based biopesticides have become a vital element in pest management strategies. Vip3 family proteins from Bacillus thuringiensis have distinct characteristics from known insecticidal Cry toxins and show efficient insecticidal activity against several detrimental lepidopteran pests. They are considered to be a promising toxic candidate for the management of various detrimental pests. In this study, we found that in addition to the preliminary digestion sites lysine, there are multiple cleavage activation sites in the linker region between domain I (DI) and DII of Vip3Aa. We further demonstrated that by adding more cleavage sites between DI and DII of Vip3Aa, its proteolysis efficiency by midgut proteases can be significantly increased, and correspondingly enhance its insecticidal activity against Spodoptera frugiperda and Helicoverpa armigera larvae. Our study promotes the understanding of the insecticidal mechanism of Vip3 proteins and illustrates an easily implementable strategy to increase the insecticidal potency of Vip3Aa. This facilitates their potential future development and efficient application for sustainable agriculture.

Summary: Background: Metropolitan areas have complex trade linkages internally and externally. This complexity stimulates the unequal spatial transfer of environmental health consequences, economy, and employment embodied in internal trade or trade with the outside regions, resulting in unequal exchange. Existing research has rarely discussed this issue at a refined scale, hindering targeted inequity alleviation policies. Methods: We conducted a mixed-methods study, focusing on the most polluted metropolitan area in the world, the Beijing-Tianjin-Hebei region of China, and developed an integrated modelling framework to downscale the analysis of the trade-driven unequal transfer of PM2·5- related premature deaths, value added, and job opportunities to the city scale within Beijing-Tianjin-Hebei. The study couples a nested Multi-Regional Input-Output model table containing data from 13 Beijing-Tianjin-Hebei cities and 28 outer provinces in 2017 with a bottom-up emission inventory, value added and employment statistical data, the Weather Research and Forecasting-Comprehensive Air Quality Model with Extensions, the Global Exposure Mortality Model, and human capital methods. We also constructed two indices measuring unequal exchanges between PM2·5-related deaths and economic and employment gains embodied in trades between cities in Beijing-Tianjin-Hebei and trades with outside regions. Findings: The Beijing-Tianjin-Hebei region as a single entity shifted 14 985 (95% CI 12 800–16 948) net deaths to regions outside the Beijing-Tianjin-Hebei through trade, most of which occurred in the central region of China. The industrial-based peripheral Beijing-Tianjin-Hebei cities suffered the most serious inequities when trading with other Beijing-Tianjin-Hebei cities and outside regions. While gaining equivalent local jobs, these industrial-based peripheral cities had 250% higher PM2·5-related deaths (10·2 PM2·5-related deaths for obtaining 1000 local jobs) than core cities (2·9 PM2·5-related deaths for obtaining 1000 local jobs) and 57·7% higher PM2·5-related deaths than agricultural-based peripheral cities (6·5 PM2·5-related deaths for obtaining 1000 local jobs). While gaining equivalent value added, industrial-based peripheral cities had 50·6% higher PM2·5-related deaths (¥13·9 of reduced human capital due to PM2·5-related premature deaths to obtain ¥1000 local value added) than core cities (¥9·2 of reduced human capital due to PM2·5-related premature deaths to obtain ¥1000 local value added) and 67·4% higher PM2·5-related deaths than agricultural-based peripheral cities (¥8·3 of reduced human capital due to PM2·5-related premature deaths to obtain ¥1000 local value added). Interpretation: Treating metropolitan areas as a single entity obscured internal heterogeneity, potentially misleading policy makers into imposing strict regulations on the whole metropolitan area to alleviate the inequities it posed on outside regions. However, several peripheral Beijing-Tianjin-Hebei cities were disadvantaged in their trade with core Beijing-Tianjin-Hebei cities and outside regions. Therefore, policies should be tailored for particular cities within metropolitan areas. Future targeted policies should include, but not be limited to, making ecological compensations and incorporating the environment and health costs into the price of pollution-intensive goods and services. Funding: National Key Research and Devlopment Program of China, National Natural Science Foundation of China, and Jiangsu Natural Science Foundation

Fusion-associated small transmembrane (FAST) proteins can promote cell fusion, alter membrane permeability and trigger apoptosis to promote virus proliferation in orthoreoviruses. However, it is unknown whether FAST proteins perform these functions in aquareoviruses (AqRVs). Non-structural protein 17 (NS17) carried by grass carp reovirus Honghu strain (GCRV-HH196) belongs to the FAST protein family, and we preliminarily explored its relevance to virus infection. NS17 has similar domains to FAST protein NS16 of GCRV-873, comprising a transmembrane domain, a polybasic cluster, a hydrophobic patch and a polyproline motif. It was observed in the cytoplasm and the cell membrane. Overexpression of NS17 enhanced the efficiency of cell-cell fusion induced by GCRV-HH196 and promoted virus replication. Overexpression of NS17 also led to DNA fragmentation and reactive oxygen species (ROS) accumulation, and it triggered apoptosis. The findings illuminate the functions of NS17 in GCRV infection, and provide a reference for the development of novel antiviral strategies.

Docetaxel is one of the most commonly used drugs in prostate cancer (PCa) chemotherapy, but its therapeutic effect in PCa is usually limited due to its drug resistance. APOBEC3B is a DNA cytosine deaminase that can alter biological processes, including chemoresistance. APOBEC3B is upregulated in various cancers. However, the biological function and underlying regulation of APOBEC3B in PCa remain unclear. In this study, we explored the role of APOBEC3B in PCa chemoresistance and the molecular mechanism of its dysregulated expression. Our results revealed that APOBEC3B was upregulated in PCa docetaxel-resistant cells, while its knockdown significantly repressed cell proliferation and docetaxel resistance of PCa cells. Bioinformatics and luciferase report analysis showed that miR-138–5p targeted APOBEC3B. In addition, miR-138–5p overexpression impeded cell proliferation and docetaxel resistance in PCa, while miR-138–5p inhibitors reversed this process. Further studies showed that upregulation of APOBEC3B expression in docetaxel-resistant cells overexpressing miR-138–5p could desensitize PCa cells to docetaxel treatment. Taken together, miR-138–5p regulates PCa cell proliferation and chemoresistance by targeting the 3′-UTR of APOBEC3B, which may provide novel insights and therapeutic targets for the treatment of PCa.

Huangqi-Danshen decoction (HDD), a Chinese herbal preparation, is effective in clinical treatment of chronic kidney disease (CKD). However, the underlying mechanism remains to be clarified. In this study, we aimed to investigate the role of HDD in the regulation of renal glucose metabolism in a CKD mouse model. The 0.2% adenine-induced CKD mouse model was administered HDD extract at a dose of 6.8 g/kg/day for 4 weeks. Detection of renal glucose metabolites was performed by ultra-performance liquid chromatography-tandem mass spectrometry. The expression of renal fibrosis and glucose metabolism-related proteins was tested by Western blotting, immunohistochemistry, and immunofluorescence. The results showed that HDD treatment could significantly reduce serum creatinine (0.36 ± 0.10 mg/dL vs. 0.51 ± 0.07 mg/dL, P

Pulmonary fibrosis that occurs following lung injury is a progressive and fatal disease since continual damage to lung tissue triggers the dysregulated inflammation response and accompanying abnormal healing process. Pyroptosis of alveolar macrophages has been found to play an essential role in the deterioration of lung injury and fibrosis. However, the lack of inhibitors against this inflammatory cell death in macrophages and the dense stroma pose major barriers to lung injury and fibrosis treatment. Herein, we developed an albumin-based nanoformulation to realize active delivery of formononetin (FMN) to improve the treatment of lung injury and fibrosis. The obtained nanoparticle, FMN@BSA NPs, could efficiently accumulate at the impaired lesion benefiting from the leaky vasculatures and the affinity between albumin and the overexpressed SPARC protein. Through blocking the NLRP3 inflammasome-involved pyroptosis process of macrophages, FMN@BSA NPs remarkably improved lung function and prolonged animal survival in the bleomycin (BLM)-induced lung injury and fibrosis model without noticeable side effects. Meanwhile, we proved FMN as a pyroptosis inhibitor and the corresponding lipid metabolism-related mechanisms through multi-omics analysis. This study first employed an albumin-based nanoparticle to deliver the pyroptosis inhibitor to the impaired lung tissue actively, providing a promising strategy for lung injury and fibrosis treatment.

Objective: The aim of this systematic review was to evaluate the efficacy of laser therapy in temporomandibular disorders (TMD). Methods: Randomized controlled trials (RCTs) in regard to this issue were searched in electronic databases. Three investigators independently screened the eligible studies, and the quality of the included studies was assessed according to the risk of bias tool recommended by the Cochrane handbook. The primary outcome measure was the degree of pain, reported on a visual analog scale (VAS), and the secondary outcome measures were TMJ function, including maximum active vertical opening (MAVO), maximum passive vertical opening (MPVO), left and right lateral movement (LLE, RLE). Pooled effect sizes were calculated using random effects models and 95% confidence interval (95% CI). Results: A total of 28 randomized controlled trials were included. Laser therapy had a more significant effect in terms of VAS (SMD=﹣1.88; 95% CI=﹣2.46 to﹣1.30; P

The nanoindentation behavior of P92 steel with thermomechanical treatment under 3.5 MeV Fe13+ ion irradiation at room temperature, 400 and 700 °C was investigated. Pop-in behavior is observed for all the samples with and without irradiation at room temperature, while the temperature dependence of pop-in behavior is only observed in irradiated samples. The average load and penetration depth at the onset of pop-in increase as the irradiation temperature increases, in line with the results of the maximum shear stress. Irradiation induced hardening is exhibited for all irradiated samples, but there is a significant reduction in the hardness of sample irradiated at 700 °C in comparison to the samples irradiated at room temperature and 400 °C. The ratio of hardness to elastic modulus for all samples decreases with increasing penetration depth except for samples at 700 °C. With the increasing of irradiation temperature, the ratio of the irreversible work to the total work gradually decreases. In contrast, it increases for samples without irradiation.

Self-assembling carrier-free nanodrugs are attractive agents because they accumulate at tumor by an enhanced permeability and retention (EPR) effect without introduction of inactive substances, and some nanodrugs can alter the immune environment. We synthesized a peptidyl arginine deiminase 4 (PAD4) molecular inhibitor, ZD-E-1M. It could self-assembled into nanodrug ZD-E-1. Using confocal laser scanning microscopy, we observed its cellular colocalization, PAD4 activity and neutrophil extracellular traps (NETs) formation. The populations of immune cells and expression of immune-related proteins were determined by single-cell mass cytometry. ZD-E-1 formed nanoflowers in an acidic environment, whereas it formed nanospheres at pH 7.4. Accumulation of ZD-E-1 at tumor was pH-responsive because of its pH-dependent differences in the size and shape. It could enter the nucleus and bind to PAD4 to prolong the intracellular retention time. In mice, ZD-E-1 inhibited tumor growth and metastasis by inhibiting PAD4 activity and NETs formation. Besides, ZD-E-1 could regulate the ratio of immune cells in LLC tumor-bearing mice. Immunosuppressive proteins like LAG3 were suppressed, while IFN-γ and TNF-α as stimulators of tumor immune response were upregulated. Overall, ZD-E-1 is a self-assembling carrier-free nanodrug that responds to pH, inhibits PAD4 activity, blocks neutrophil extracellular traps formation, and improves the tumor immune microenvironment.

Background: EGFR amplification and/or mutation are found in more than half of the cases with glioblastoma. Yet, the role of chromatin interactions and its regulation of gene expression in EGFR-amplified glioblastoma remains unclear. Methods: In this study, we explored alterations in 3D chromatin organization of EGFR-amplified glioblastoma and its subsequent impact by performing a comparative analysis of Hi-C, RNA-seq, and whole-genome sequencing (WGS) on EGFR-amplified glioblastoma-derived A172 and normal astrocytes (HA1800 cell line). Results: A172 cells showed an elevated chromatin relaxation, and unexpected entanglement of chromosome regions. A genome-wide landscape of switched compartments and differentially expressed genes between HA1800 and A172 cell lines demonstrated that compartment activation reshaped chromatin accessibility and activated tumorigenesis-related genes. Topological associating domain (TAD) analysis revealed that altered TAD domains in A172 also contribute to oncogene activation and tumor repressor deactivation. Interestingly, glioblastoma-derived A172 cells showed a different chromatin loop contact propensity. Genes in tumorigenesis-associated signaling pathways were significantly enriched at the anchor loci of altered chromatin loops. Oncogene activation and tumor repressor deactivation were associated with chromatin loop alteration. Structure variations (SVs) had a dramatic impact on the chromatin conformation of EGFR-amplified glioblastoma-derived tumor cells. Moreover, our results revealed that 7p11.2 duplication activated EGFR expression in EGFR-amplified glioblastoma via neo-TAD formation and novel enhancer-promoter interaction emergence between LINC01446 and EGFR. Conclusions: The disordered 3D genomic map and multi-omics data of EGFR-amplified glioblastoma provide a resource for future interrogation of the relationship between chromatin interactions and transcriptome in tumorigenesis.

The plant UV-B photoreceptor UV RESISTANCE LOCUS 8 (UVR8) exists as a homodimer in its inactive ground state. Upon UV-B exposure, UVR8 monomerizes and interacts with a downstream key regulator, the CONSTITUTIVE PHOTOMORPHOGENIC 1/SUPPRESSOR OF PHYA (COP1/SPA) E3 ubiquitin ligase complex, to initiate UV-B signaling. Two WD40 proteins, REPRESSOR OF UV-B PHOTOMORPHOGENESIS 1 (RUP1) and RUP2 directly interact with monomeric UVR8 and facilitate UVR8 ground state reversion, completing the UVR8 photocycle. Here, we reconstituted the RUP-mediated UVR8 redimerization process in vitro and reported the structure of the RUP2-UVR8W285A complex (2.0 Å). RUP2 and UVR8W285A formed a heterodimer via two distinct interfaces, designated Interface 1 and 2. The previously characterized Interface 1 is found between the RUP2 WD40 domain and the UVR8 C27 subregion. The newly identified Interface 2 is formed through interactions between the RUP2 WD40 domain and the UVR8 core domain. Disruption of Interface 2 impaired UV-B induced photomorphogenic development in Arabidopsis thaliana. Further biochemical analysis indicated that both interfaces are important for RUP2-UVR8 interactions and RUP2-mediated facilitation of UVR8 redimerization. Our findings suggest that the two-interface-interaction mode is adopted by both RUP2 and COP1 when they interact with UVR8, marking a step forward in understanding the molecular basis that underpins the interactions between UVR8 and its photocycle regulators.

To expand crop planting areas, reestablishment of crop latitude adaptation based on genetic variation in photoperiodic genes can be performed, but it is quite time consuming. By contrast, a crop variety that already exhibits multi-latitude adaptation has the potential to increase its planting areas to be more widely and quickly available. However, the importance and potential of multi-latitude adaptation of crop varieties have not been systematically described. Here, combining daylength-sensing data with the cropping system of elite rice and maize varieties, we found that varieties with gradual daylength sensing coupled with optimum cropping modes have an enhanced capacity for multi-latitude adaptation in China. Furthermore, this multi-latitude adaptation expanded their planting areas and indirectly improved China’s nationwide rice and maize unit yield. Thus, coupling the daylength-sensing process with optimum cropping modes to enhance latitude adaptability of excellent varieties represents an exciting approach for deploying crop varieties with the potential to expand their planting areas and quickly improve nationwide crop unit yield in developing countries.

Summary: Genome-wide mapping of transcription factors (TFs) is critical to understand their functions. In chromatin immunoprecipitation (ChIP)-seq assay, it’s challenging to study recruitment of low-abundant TFs transiently boud to the genome. Here, we present an optimized protocol using ChIP Next-Gen Seq Sepharose (Staph-seq) to efficiently pull down chromatin complexes. The double size selection promotes sensitive capture of genome-wide protein-DNA associations while eliminating potential Staph A contamination, which is a common problem in protocols using Staph A cells.For complete details on the use and execution of this protocol, please refer to Tao et al. (2020).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

The inflammatory microenvironment created by macrophages has been proven critical for bone regeneration. Both tantalum nanoparticles and micron particles have been applied to bone tissue engineering and have achieved good efficacy, but their effects on immune microenvironment remain unclear. Herein, we explored the different effects between nano- and micro-tantalum particles on the innate immunity of macrophages in vitro and in vivo. RAW 264.7 ​cells were co-cultured with nano- and micro-tantalum particles under inflammatory conditions to evaluate the effects on the morphology and behavior of macrophages. Air pouch model was used to evaluate the material-induced macrophage polarization in vivo. Compared to the tantalum micron particles (TaMPs), the morphology of macrophages was more similar to the M2 phenotype in co-culture with tantalum nanoparticles (TaNPs). At the same time, the TaNPs could also decrease the gene expression of interleukin-1β (IL-1β), tumor necrosis factor-α(TNF-α), inducible nitric oxide synthase (iNOS), and increase the expression of transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10). Furthermore, the air pouch model showed more M2 macrophage infiltration under the intervention of TaNPs. Our findings demonstrated that TaNPs could significantly increase the polarization of M2 macrophages and decrease the macrophage polarization to the M1 phenotype under the inflammatory microenvironment, showing better immunomodulatory properties.

Bone nonunion or delayed union, caused by stripping or injuring of periosteum, is the most common sequelae of segmental bone defects. The preservation of periosteum, or the use of periosteal grafts, can significantly improve the integration of bone graft, speeding up the process of bone reconstruction. However, in most cases, periosteum cannot be preserved with bioactivity. Thus, it is pivotal to develop artificial periosteum. In this study, artificial periosteum of PLGA/MgO/Quercetin was prepared by electrospinning. PLGA/MgO/Quercetin membranes were shown to have a highly porous surface and microstructure, as observed by scanning electron microscopy. Along with excellent biocompatibility, PLGA/MgO/Quercetin membranes promoted cell proliferation and migration, as well as osteogenic differentiation of BMSCs (Bone marrow mesenchymal stem cells) in a dose-dependent manner through the activation of Wnt/β-Catenin pathway. The PLGA/MgO/Quercetin membranes, with an appropriate concentration of quercetin (

ABSTRACT: This experiment was conducted to investigate the antibacterial effects of essential oils (EO) in vitro and the influence of EO on growth performance, intestinal morphology and oxidation resistance and cecal microflora of yellow-feathered broilers. A total of 720 one-day-old male yellow feather broilers were randomly assigned into 4 treatments with 6 replicate cages of 30 broilers each. The groups were as follows: CON group (basal diet), EO200 group (basal diet + 200 mg/kg EO), EO400 group (basal diet + 400 mg/kg EO), and EO600 group (basal diet + 600 mg/kg EO). The experiment lasted for 48 d. Results showed that the growth and biofilm formation of avian pathogenic E. coli O78 and Salmonella pullorum were limited by adding EO to the diet (P < 0.05). Besides, birds fed with EO had greater (P < 0.05) average daily feed intake (ADFI), average daily gain (ADG), and body weight (BW) during d 1 to 21, 22 to 42, and 1 to 48 and lower (P < 0.05) feed: gain (F:G) than those fed with basal diet during d 22 to 42 and 1 to 48. Moreover, the activity of antioxidant enzyme and the intestinal permeability were improved in the EO400 and EO600 groups rather than the CON group on d 21 (P < 0.05). There were significant differences in cecal microbial composition and enrichment of metabolic pathways of birds among all groups by 16S-based sequencing. In summary, some dose of EO improved bacteriostatic ability, antioxidant ability, and intestinal health of broilers which contributed to the growth performance improvement of yellow-feathered broilers, which can be a promising antibiotic alternative for improving poultry production.

ABSTRACT: The objective of this study was to compare the immunomodulatory effects of the chicken soups prepared with the native free-range chickens and the commercial caged broilers in the immunosuppressive mice. The immunosuppressive mice model was established by the intraperitoneal injection of 100 mg of cyclophosphamide (CTX) per kg body weight. The powders of Gushi Chicken Soup (GCS), Honglashan Chicken Soup (HCS), and Cobb Broiler Soup (CBS) were prepared by high-pressure stewing followed by spray drying. The chicken soups' nutrient content and the effects of three chicken soups on the body weight, organ index, blood index, and serum cytokine and immunoglobulin contents in the immunosuppressive mice were determined. The three chicken soups promoted the recovery of immunosuppressive mice, but the expression mechanisms were different. The GCS was more effective than the HCS and CBS in restoring blood index, promoting cytokine secretion, and increasing immunoglobulin content (P < 0.05). The HCS stimulated the Th1-type immune response and promoted immunoglobulin secretion (P < 0.05), while the CBS increased the production of CD4+ and promoted the T-cell functions better than other soups (P < 0.05). Although soups from the native free-range chickens and the commercial caged broilers showed distinctly different mechanisms in promoting immunity, both could be used as potential immunomodulators.

Constructing payments for ecosystem services (PES) for inter-basin water transfer is one of the effective means to adjust the interest relationship and promote low-carbon development in the region. The inter-basin water transfer ecological compensation policy (IWTECP) in China is a PES project facing a series of problems. To this end, we applied contingent valuation method (CVM) to examine the willingness to pay (WTP) in water-receiving area and willingness to accept (WTA) in water-source area of the eastern route of South-to-North Water Transfer Project, China. The WTP and WTA values were 206.29 RMB/(person·year) (USD 32.37/(person·year)) and 443.29 RMB/(person·year) (USD 69.55/(person·year)) respectively. Bayesian network model was employed to explore the influencing factors, it was found that educational background, per capita monthly household income and the recognition of the importance of the project to the city or the country had the greater influence on WTP, while age, per capita monthly household income and the influence of project on personal life were the most influential factors on WTA. By comparing the influencing factors of WTP and WTA, the intention preference of the respondents was discussed. Then, SWOT matrix analysis method was adopted to put forward incentive mechanism from the perspectives of internal public background and external environmental policies. Our results could provide incentive policies for target groups of consumers, improve the efficiency of ecological protection, and promote the reform of the IWTECP.

The diversity of waterbirds is threatened, and haemosporidian parasite infection is considered one of the most important causative factors. However, to date, only a few studies focusing on specific parasite species have been carried out, which cannot reflect the general patterns at the community level. To test whether the reported haemosporidian diversity in waterbirds is underestimated, we estimated the prevalence and lineage diversity of avian haemosporidian parasites in 353 waterbirds from 26 species in the Tumuji National Nature Reserve, Northeast China, as well as the host-parasite associations. According to the molecular analysis of cytochrome b (cyt b) barcode sequences, 28.3% of the birds were infected by 49 distinct parasite lineages, including 11 Plasmodium, 12 Haemoproteus, and 26 Leucocytozoon lineages, of which 39 were novel. The highest prevalence was contributed by Leucocytozoon (13.31%), followed by Plasmodium (13.03%) and Haemoproteus (4.25%), which suggested that waterbirds were infected to a lesser extent by Haemoproteus than by the other two genera. Among the most sampled birds, species belonging to Anatidae appeared to be susceptible to Leucocytozoon but resistant to Plasmodium, while Rallidae presented the opposite pattern. On the phylogenetic tree, most of the Leucocytozoon lineages detected in Anatidae clustered together and formed two well-supported clades, while lineages restricted to Gruidae were distantly related to other parasites in all three genera. SW5 was the most abundant lineage and therefore might be a major threat to waterbirds; among the hosts, the common coot harboured the highest diversity of parasite lineages and thus could act as a reservoir for potential transmission. This is the first study of avian haemosporidian infections in a wild waterbird community in Asia. Our findings have doubled the number of lineages recorded in waterbirds, broadened our understanding of host-parasite associations, and addressed the importance of studying haemosporidian infections in wild waterbird conservation.

Phosvitin (PV) from egg yolk is an excellent substrate for the production of phosphopeptides, which have a strong calcium chelating capacity and promoting calcium absorption and bone mineralization. This study investigated the effect of PV hydrolysates produced using a effective preparation method (high temperature (121°C) and mild pressure (0.1 MPa), HTMP) or HTMP pretreatment and trypsin hydrolysis combination (HTMP-PV18) on the physiology of an osteoblast MC3T3-E1 cells line. The proliferation, apoptosis, and differentiation of MC3T3-E1 cells were analyzed using the CCK-8, flow cytometry, and RT-PCR reactions, respectively. Both the HTMP-PV and HTMP-PV18 increased the proliferation, and inhibited the apoptosis of MC3T3-E1 cells significantly. The HTMP-PV increased the proliferation of MC3T3-E1 cells by 147.12 ± 2.11% and the HTMP-PV18 by 136.43 ± 4.51%. In addition, the HTMP-PV and HTMP-PV18 effectively promoted the expression of genes related to the OPG/RANKL signaling channel during cell differentiation. This indicated that both the HTMP-PV and HTMP-PV18 have the potential to promote bone mineralization by improving the proliferation and differentiation of osteoblastic cells.

Rice, wheat and maize are the main staple food crops to ensure the food security in China with diversified climate condition, cropping system and environmental and socio-economic factors across provinces. Spatial variation of technical efficiency in farmers’ field is helpful to understand the potential to improve farmers’ yield given the inputs level and reduce the yield gap. The study is based on a large-scale farm household survey which covered 1 218 rice farmers, 3566 wheat farmers and 2 111 maize farmers in the main producing areas. The results indicate that rice farmers are with very high technical efficiency level, nearly 0.9 on average, with little room to improve the efficiency of agricultural inputs. Similar results have been found in wheat and maize farmers’ fields, although the technical efficiency levels are lower than that of rice farmers while still at a high level with obvious variation across regions. Farmers with higher yield level also achieve better technical efficiency in most locations. Both local environmental and socio-economic factors significantly affect farmers’ technical efficiency. In the context of urbanization and economic development, improved and new agricultural technologies need to be prioritized and facilitated to improve cereal yield at farm level.

Dual-cooled annular fuel allows a significant increase in power density while maintaining or improving safety margins. However, the dual-cooled design brings much higher Zircaloy charge in reactor core, which could cause a great threaten of hydrogen explosion during severe accidents. Hence, an innovative fuel combined dual-cooled annular geometry and SiC cladding was proposed for the first time in this study. Capabilities of fuel design and behavior simulation were developed for this new fuel by the upgrade of FROBA-ANNULAR code. Considering characteristics of both SiC cladding and dual-cooled annular geometry, the basic fuel design was proposed and preliminary proved to be feasible. After that, a design optimization study was conducted, and the optimal values of as-fabricated plenum pressure and gas gap sizes were obtained. Finally, the performance simulation of the new fuel was carried out with the full consideration of realistic operation conditions. Results indicate that in addition to possessing advantages of both dual-cooled annular fuel and accident tolerant cladding at the same time, this innovative fuel could overcome the brittle failure issue of SiC induced by pellet-cladding interaction.

ABSTRACT: The aim of the present study was to evaluate the effect of magnolol (MAG) on growth performance, meat quality, oxidative capacity, and intestinal microbiota in the yellow-feather broilers. A total of 360 one-day-old male yellow-feather broiler chicks were allocated into 5 groups of 6 replicates and 12 chickens per replicate, were fed a basal diet supplemented with 0 (Control group, CON), 100, 200, 300, or 400 mg/kg MAG for 51 d. The results showed that dietary supplementation with 200 and 300 mg/kg MAG increased the average daily gain (ADG) but decreased feed to gain ratio (F/G) during the overall periods (P < 0.05). Dietary MAG increased significantly the redness value (a∗) of the breast muscle (P < 0.05), and decreased the water loss rate and shear force of the breast meat (P < 0.05). MAG supplement reduced the malondialdehyde (MDA) levels, and increased the glutathione (GSH), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) levels in breast muscle and jejunum. PCR analysis showed that MAG increased the levels of NF-E2-related factor 2 (Nrf2), NAD(P)H/quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), glutathione-S transferase (GST), glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase modifier subunit (GCLM), and SOD expressions (P < 0.05). Analysis of differential enrichment of gut microbiota found that Faecalibacterium in the cecum of MAG supplemented broilers increased, and Coprobacillus has decreased (P < 0.05). In conclusion, MAG improved growth performance, meat quality of the broilers and antioxidant capacity, and modulated gut microbiota homeostasis.