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Abstract Two-dimensional (2D) magnetic materials are of not only fundamental scientific interest but also promising candidates for numerous applications. However, so far only a few intrinsic magnets with long-ranged order down to the 2D limit have been experimentally established. Here, we report that the intrinsic 2D ferromagnetism can be realized in van der Waals (vdW) Fe3GaTe2 nanoflake down to monolayer. By measuring the Hall resistance and magnetoresistance, we demonstrate that the Fe3GaTe2 monolayer exhibits 2D hard ferromagnetism with record-high Cure temperature (T c) of 240 K for the monolayer of known intrinsic ferromagnets. Both of square-shaped hysteresis loops with near-vertical jump in anomalous Hall effect (AHE) and the negative magnetoresistance (NMR) behavior with an applied out-of-plane magnetic field reveal robust perpendicular magnetic anisotropy (PMA) in Fe3GaTe2 nanoflakes down to the monolayer limit. Furthermore, we find the intrinsic mechanism that stems from the Berry curvature of electronic bands dominates AHE of nanoflakes in the low temperature range. Our results not only provide an excellent candidate material for next-generation spintronic applications, but also open up a platform for exploring physical mechanisms in 2D ferromagnetism.

Vitis amurensis grape cultivars and hybrids are mainly used to make wines in Northeast Asia with a cold winter. Anthocyanidin glucosylation at 5-O position catalyzed by 5-O-glucosyltransferase (5GT) in grape skins is crucial for color stability of red wines. To study 5GT functions in anthocyanidin diglucosides synthesis of V. amurensis, 20 5GTs were preliminarily identified from a genome-wide characterization of the UDP-glycosyltransferase family according to the reported 5GTs, which were also performed phylogenetic and bioinformatics analysis. Two important 5GTs, Vitvi0900582.t01 and Vitvi05g01269.t01, were screened through analyses of anthocyanidin diglucosides accumulation and gene expression in berry skins of three representative grape cultivars with significant differences in anthocyanin glycosylation. Fourteen alleles of each of the 5GTs were cloned from 14 V. amurensis cultivars and hybrids as well as from V. vinifera ‘Cabernet Sauvignon’, and sequence analysis and functional prediction were performed. From three perspectives of phenotype, transcriptional level, and genotype, it has been found that the functional allele at the Vitvi0900582.t01 locus of Chr 9 played a decisive role in the synthesis of abundant anthocyanidin diglucosides in V. amurensis. In addition, the trace anthocyanidin diglucosides detected in V. vinifera ‘Cabernet Sauvignon’ were led by the functional allele at the Vitvi05g01269.t01 locus of Chr 5. This study provides preliminary data for further research on the regulatory mechanism of anthocyanidin diglucosides in the grapes with the V. amurensis pedigree to improve their wine quality in future breeding efforts.

Molecular iron phthalocyanine (FePc) bearing a single‐atom Fe–N4 moiety is a high‐profile non‐platinum catalyst toward the oxygen reduction reaction (ORR), but its unsatisfactory activity and inadequate stability hinder the practical application. Herein, a novel strategy by hybridizing FePc with fullerene‐derived intrinsic defect‐rich carbon to improve its ORR activity and stability is reported. Via alkali‐assisted thermal pyrolysis, C60 molecules are disintegrated into tiny fragments that then restructure into pentagon‐ and edge‐rich carbon (FC). Utilizing FC as a support of FePc leads to a significantly improved ORR activity compared to other supports including reduced graphene oxide and carbon nanotube that hold distinct structural features. The optimized FePc/FC with a Fe loading of 3 wt% presents a half‐wave potential of 0.917 V, far beyond that of Pt/C (0.846 V), via selective four‐electron ORR pathway and excellent stability under accelerated stress test. The practical applicability of FePc/FC is also demonstrated as a high‐performing cathode catalyst of aqueous zinc–air batteries. It is, for the first time, explicitly disclosed that strong interactions between FePc molecules and intrinsic carbon defects (e.g., pentagons and edges) not only strengthen the anchoring effect of supported FePc but also enhance the intrinsic ORR activity of single‐atom Fe–N4 sites.

Abstract Immune checkpoint blockade (ICB) has shown considerable promise for treating various malignancies, but only a subset of cancer patients benefit from immune checkpoint inhibitor therapy because of immune evasion and immune-related adverse events (irAEs). The mechanisms underlying how tumor cells regulate immune cell response remain largely unknown. Here we show that hexokinase domain component 1 (HKDC1) promotes tumor immune evasion in a CD8+ T cell-dependent manner by activating STAT1/PD-L1 in tumor cells. Mechanistically, HKDC1 binds to and presents cytosolic STAT1 to IFNGR1 on the plasma membrane following IFNγ-stimulation by associating with cytoskeleton protein ACTA2, resulting in STAT1 phosphorylation and nuclear translocation. HKDC1 inhibition in combination with anti-PD-1/PD-L1 enhances in vivo T cell antitumor response in liver cancer models in male mice. Clinical sample analysis indicates a correlation among HKDC1 expression, STAT1 phosphorylation, and survival in patients with hepatocellular carcinoma treated with atezolizumab (anti-PD-L1). These findings reveal a role for HKDC1 in regulating immune evasion by coupling cytoskeleton with STAT1 activation, providing a potential combination strategy to enhance antitumor immune responses.

Abstract Objective To explore the factors influencing C-reactive protein (CRP) status in neonates on admission after birth. Methods 820 newborns born and hospitalized at Xiangya Hospital of Central South University from Jan. 2020 to Dec. 2020 were retrospectively analyzed. Maternal medical history and medication use during pregnancy, neonatal demographic information and status at birth were collected through the electronic medical record system. Statistical software was used to analyze the possible relationship between perinatal factors and CRP on admission after birth. Results A total of 820 neonates were analyzed, including 463 males and 357 females with a mean gestational age (GA) of 36.07 ± 3.30 weeks. (1) Multifactor Logistic regression analysis: larger GA (OR: 1.13, 95%CI: 1.00-1.28, P = 0.042), premature rupture of membranes (PROM) ≥ 18 h (OR: 2.39, 95%CI: 1.35–4.23, P = 0.003) and maternal autoimmune diseases (OR: 5.30, 95%CI: 2.15–13.07, P

Abstract Background To investigate the association between sex and neonatal respiratory distress syndrome (NRDS). Methods Neonates born at our hospital and transferred to the neonatal department within 1 h were retrospectively analyzed. Depending on whether they developed NRDS during their hospital stay, the neonates was divided into NRDS and non-NRDS groups. There were 142 neonates in the NRDS group (95 males and 47 females) and 310 neonates in the non-NRDS group (180 males and 140 females). The neonates’ data on gestational age (GA), sex, birth weight, white blood cell count (WBC), platelet count (PLT), C-reactive protein (CRP), total immunoglobulin M (total IgM), gestational diabetes mellitus(GDM), antenatal steroids use, meconium-stained amniotic fluid, and preterm premature rupture of membranes(PPROM) were gathered. Results 452 neonates (265 males and 187 females) were involved for the purpose of collecting basic characteristic. Multivariate analysis, males had a 1.87 times higher risk of NRDS than females (P

The inefficiency of grain refinement processes has traditionally been attributed to the limited utilization of heterogeneous nucleation particles within master alloy systems, resulting in the formation of abundant inactive particles. This study aims to investigate the alternative influences of particles by incorporating external micrometer-sized TiB2 particles into the grain refinement process. Through a series of experiments, the refinement efficiency, grain refinement mechanism, and resultant microstructure of TiB2 particle-induced grain refinement specimens are comprehensively examined using various microscopy and analytical techniques, including polarization microscopy (OM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and transmission electron microscopy (TEM). Our findings demonstrate a direct correlation between increased levels of TiB2 particles and enhanced grain refinement efficiency. Moreover, the microstructure analysis reveals the distribution of TiB2 particles along grain boundaries, forming a coating due to self-assembly phenomena, while regions with a lower particle content may exhibit irregular grain structures. DSC analysis further confirms reduced undercooling, indicating the occurrence of heterogeneous nucleation events. However, TEM observations suggest that heterogeneous nucleation is not significantly influenced by the growth restriction factor attributed to TiAl3 2DC compounds. The grain refinement mechanism involving TiB2 particles is elucidated to entail both heterogeneous nucleation and physical growth restriction effects. Specifically, a reduction in average grain size is attributed not only to heterogeneous nucleation but also to the physical growth restriction effect facilitated by the TiB2 particle coating. This study offers insights into leveraging particles that do not participate in heterogeneous nucleation within master alloy-based grain refinement systems.

Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid commonly used for treating cholestatic liver disease. However, its efficacy on non-alcoholic steatohepatitis (NASH) was controversial. This study aimed to investigate the impact of a high dosage of UDCA on a mouse model of NASH. Forty 6-week-old mice were fed a high-fat high-cholesterol (HFHC) diet for 12 weeks to establish a mouse model of NASH, and then divided into four groups: two groups transitioned to a normal diet, and the other two groups maintained the HFHC diet. Each group was administered a daily dosage of 300 mg/kg of UDCA or saline for a period of 8 weeks. The 16 s ribosomal RNA genes extracted from mice fecal pellets were sequenced using next-generation sequencing techniques. Serum bile acid profiles were quantified using liquid chromatography electrospray ionization tandem mass spectrometry method. The results showed that UDCA treatment ameliorated liver inflammation, without affecting liver fibrosis. UDCA treatment reduced the relative abundance of the genera Bacteroides, Parabacteroides, and Intestinimonas, whereas increased the relative abundance of the genera norank_f_Muribaculaceae and Parasutterella in the HFHC-maintaining groups. The serum levels of total bile acids and total primary bile acids increased, whereas those of endogenous primary bile acids decreased after UDCA treatment. Correlation analysis showed that primary bile acids were negatively correlated with the genera norank_f_Christensenellaceae and unclassified_f_Ruminococcaceae. In conclusion, a high dosage of UDCA can alleviate liver inflammation, probably by modifying the composition of gut microbiota and serum bile acid profiles in NASH mice.

Spirulina is widely known as the “Super Nutritious Food of the Future” due to its exceptional nutritional properties. In this article, we investigated the effects of fermentation using a combination of Lactobacillus acidophilus KDB-03 and Kluyveromyces marxianus GDMCC 2.119 on Spirulina. Fermentation significantly increased the total flavonoid and phenol levels in Spirulina, and enhanced the 2,2-diphenyl-1-picrylhydrazyl free radical scavenging capacity and ferric-reducing antioxidant power. Untargeted ultra-performance liquid chromatography-electrospray tandem mass spectrometry-based metabolomics and gas chromatography-ion mobility spectrometry analysis revealed alterations in the metabolites and flavor components of fermented Spirulina (FS). Furthermore, a mice experiment demonstrated that FS could effectively alleviate metabolism-associated fatty liver disease (MAFLD) by regulating liver metabolism, intestinal flora, and facilitating communication between the liver and gut. These findings suggest that fermentation could be a innovative approach to enhance the diversity of Spirulina products, and potentially be used as a strategy for the prevention and treatment of MAFLD.

Abstract Purpose We assessed the efficiency of low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) incorporated biomimetic calcium phosphate on β-tricalcium phosphate (β-TCP) (rhBMP-2/BioCaP/β-TCP) on bone formation in a model of socket preservation using cone beam computed tomography (CBCT) scanning and histological examination. Methods Forty patients undergoing minimally invasive single-root tooth extraction for dental implantation were randomized to three groups according to the material used for socket preservation: filling with rhBMP-2/BioCaP/β-TCP, β-TCP, or natural healing (kept unfilled) (controls). The alveolar sockets (including the control group) were covered by two-layer collagen membranes and sutured. Two CBCT scans were taken, one immediately after socket preservation procedure (baseline) and another 6 weeks later. Gray values (GVs) obtained from CBCT were recorded. During insertion of the dental implant, biopsies were taken and analyzed histologically for new bone formation, residual material, and unmineralized bone tissue at the core of the biopsy. Results The mean (± standard deviation) changes of GVs of the CBCT scans at the central area of filled materials were as follows: 373.19 ± 157.16 in the rhBMP-2/BioCaP/β-TCP group, 112.26 ± 197.25 in the β-TCP group, and -257 ± 273.51 in the control group. The decrease of GVs in the rhBMP-2/BioCaP/β-TCP group as compared with the β-TCP group was statistically significant (P

Better torque performance and higher reliability have long been the focus of research for slotted limited-angle torque motors (LATMs), which are primarily used to position first-stage valves in electrohydraulic servosystems. This paper presents a high reliability axial-flux slotted LATM with quasi-Halbach array for torque performance improvement including constant torque range (CTR) and output torque. Firstly, the structure with two sets of windings and the operation principle of the proposed slotted LATM is analyzed. Secondly, a brief design procedure is presented, the structure selections of open slot and double-stator single-rotor (DSSR) interior rotor with surface mounted quasi-Halbach permanent magnet (PM) array are illustrated, and the geometric parameters are optimized to obtain the optimal design of the proposed slotted LATM. Then, 3-D finite-element method (FEM) is employed to compare the proposed slotted LATM with the conventional surface mounted PM slotted LATM in terms of cogging torque, no-load back EMF, and output torque, and the results show that the proposed LATM with quasi-Halbach array has a 10% improvement in output torque and a 25% improvement in CTR. Meanwhile, the flux linkages and torque performance of the two sets of windings under various conditions verify good magnetic isolation. Finally, prototypes of two different rotor types are manufactured and a series of experiments are performed to validate the analysis.

In order to minimize the disparity between visible and infrared modalities and enhance pedestrian feature representation, a cross-modality person re-identification method is proposed, which integrates modality generation and feature enhancement. Specifically, a lightweight network is used for dimension reduction and augmentation of visible images, and intermediate modalities are generated to bridge the gap between visible images and infrared images. The Convolutional Block Attention Module is embedded into the ResNet50 backbone network to selectively emphasize key features sequentially from both channel and spatial dimensions. Additionally, the Gradient Centralization algorithm is introduced into the Stochastic Gradient Descent optimizer to accelerate convergence speed and improve generalization capability of the network model. Experimental results on SYSU-MM01 and RegDB datasets demonstrate that our improved network model achieves significant performance gains, with an increase in Rank-1 accuracy of 7.12% and 6.34%, as well as an improvement in mAP of 4.00% and 6.05%, respectively.

The advantage of a reconfigurable intelligent surface (RIS) is that it optimizes the wireless signal transmission environment. It can ameliorate the high loss of high-speed railway (HSR) millimeter-wave (mmWave) communications and increase signal strength by coherently superimposing signals at the receiving end through an appropriate beamforming design. In this paper, an mmWave multiple-input multiple-output communication system for HSR is discussed. The channel modeling takes into account the Doppler effect and the properties of mmWave channels. Aiming at the problem of high coupling of optimization variables, the singular value decomposition method is utilized to decouple them and to achieve the optimal active beamforming design. The original optimization problem is then rewritten into a more manageable form through a sequence of transformations. In order to overcome the restrictions imposed by non-convex constraints, the optimal RIS phase shift is directly calculated using the Riemann gradient descent (RGD) method. In this paper, spectral efficiency (SE) is taken as the optimization objective. Considering the fast time-varying environment of HSR, a step size selection scheme with easier convergence is adopted in the RGD method to complete the joint beamforming design. The numerical simulations demonstrate that the proposed solution outperforms the semi-definite relaxation scheme and the RIS-free auxiliary scheme in terms of SE performance and computational complexity.

To address challenges related to the inadequate representation and inaccurate discrimination of pedestrian attributes, we propose a novel method for person re-identification, which leverages global feature learning and classification optimization. Specifically, this approach integrates a Normalization-based Channel Attention Module into the fundamental ResNet50 backbone, utilizing a scaling factor to prioritize and enhance key pedestrian feature information. Furthermore, dynamic activation functions are employed to adaptively modulate the parameters of ReLU based on the input convolutional feature maps, thereby bolstering the nonlinear expression capabilities of the network model. By incorporating Arcface loss into the cross-entropy loss, the supervised model is trained to learn pedestrian features that exhibit significant inter-class variance while maintaining tight intra-class coherence. The evaluation of the enhanced model on two popular datasets, Market1501 and DukeMTMC-ReID, reveals improvements in Rank-1 accuracy by 1.28% and 1.4%, respectively, along with corresponding gains in the mean average precision (mAP) of 1.93% and 1.84%. These findings indicate that the proposed model is capable of extracting more robust pedestrian features, enhancing feature discriminability, and ultimately achieving superior recognition accuracy.

Histone deacetylase 6 (HDAC6) plays a crucial role in the acetylation of non-histone proteins and is notably implicated in angiogenesis, though its underlying mechanisms were previously not fully understood. This study conducted transcriptomic and proteomic analyses on vascular endothelial cells with HDAC6 knockdown, identifying endoglin (ENG) as a key downstream protein regulated by HDAC6. This protein is vital for maintaining vascular integrity and plays a complex role in angiogenesis, particularly in its interaction with bone morphogenetic protein 9 (BMP9). In experiments using human umbilical vein endothelial cells (HUVECs), the pro-angiogenic effects of BMP9 were observed, which diminished following the knockdown of HDAC6 and ENG. Western blot analysis revealed that BMP9 treatment increased SMAD1/5/9 phosphorylation, a process hindered by HDAC6 knockdown, correlating with reduced ENG expression. Mechanistically, our study indicates that HDAC6 modulates ENG transcription by influencing promoter activity, leading to increased acetylation of transcription factor SP1 and consequently altering its transcriptional activity. Additionally, the study delves into the structural role of HDAC6, particularly its CD2 domain, in regulating SP1 acetylation and subsequently ENG expression. In conclusion, the present study underscores the critical function of HDAC6 in modulating SP1 acetylation and ENG expression, thereby significantly affecting BMP9-mediated angiogenesis. This finding highlights the potential of HDAC6 as a therapeutic target in angiogenesis-related processes.

BackgroundMalnutrition is common in patients undergoing surgery for cancers and is a risk factor for postoperative outcomes. Body composition provides information for precise nutrition intervention in perioperative period for improving patients’ postoperative outcomes.ObjectionThe aim was to determine changes in parameters of body composition and nutritional status of cancer patients during perioperative period.MethodsA total of 92 patients diagnosed with cancer were divided into gastrointestinal and non-gastrointestinal cancer group according to different cancer types. The patients body composition assessed by bioelectrical impedance vector analysis (BIVA) on the day before surgery, postoperative day 1 and 1 day before discharge. The changes between two groups were compared and the correlation between body composition and preoperative serum nutritional indexes was analyzed.ResultsThe nutritional status of all patients become worse after surgery, and phase angle (PA) continued to decrease in the perioperative period. Fat-free mass (FFM), fat-free mass index (FFMI), skeletal muscle mass (SMM), extracellular water (ECW), total body water (TBW), hydration, and body cell mass (BCM) rise slightly and then fall in the postoperative period in patients with gastrointestinal cancer, and had a sustained increase in non-gastrointestinal patients, respectively (P

Objective Establishing biocompatible, biodegradable, osteoconductive, and osteoinductive bone materials remains a challenging subject in the research of bone healing and bone regeneration. Previously, we demonstrated the osteogenic and osteoconductive effects of biomimetic calcium phosphate (BioCaP) incorporating with Icariin and/or bone morphogenetic protein 2 (BMP‐2) at orthotopic sites. Methods By implanting the BioCaP granules incorporated Icariin and/or BMP‐2 into the dorsal subcutaneous pockets of adult male Sprague‐Dawley (S‐D) rats (6‐7 weeks old), we investigated the osteoinductive efficacy of the samples. Micro‐computed tomography(micro‐CT) observations and histological slices were used to verify the osteoinduction of this system on the 2nd and 5th week. Statistical significances was evaluated using Turkey's post hoc test of one‐way analysis of variance. Results The osteoinduction of the BioCaP incorporated with BMP‐2 or both agents was confirmed as expected. BioCaP with Icariin alone could not generate bone formation at an ectopic sites. Nevertheless, co‐administration of Icariin increased bone mineral density (BMD; p < 0.01) (628mg HA/cm3 vs 570mg HA/cm3) and completely changed the distribution of newly formed bone when compared with the granules with BMP‐2 alone, even though there was no significant difference in the volume of newly formed bone. In contrast, the BioCaP with both agents (37.86%) had significantly fewer remaining materials than the other groups by the end of the fifth week (53.22%, 53.62% and 48.22%) (p < 0.01). Conclusion The co‐administration of Icariin and BMP‐2 increased BMD changed the distribution of newly formed bone, and reduced the amount of remaining materials. Therefore, Icariin can stimulate BMP‐2 when incorporated into BioCaP granules at ectopic sites, which makes it useful for bone tissue engineering.

AbstractStrawberry has high nutritional and economic value and is an important horticultural crop widely cultivated worldwide. Strawberry anthracnose is the most harmful disease in strawberry production, which causes huge production losses every year. Mining disease resistance genes and breeding high-quality strawberry varieties are the fundamental way to solve the problem of strawberry anthracnose. In this study, transcriptome analysis and disease resistance-related genes mining were targeted on strawberry anthracnose. The main results are as follows: (1) A total of 100.45 Gb clean reads were obtained, with no less than 6.26 Gb for each sample; (2) The clean reads for each sample were aligned to the reference genome efficiently at 91.30% − 92.27%; (3) 93,042 genes were annotated; (4) 16 anti-anthracnose-related genes were identified, including FaAUX1, FaARF18, FaSAUR50, FaGH3.6, FaAHP1, FaARR (3, 5 and 11), FaPYR1, FaPYL11, FaPP2C (6, 16, 24, 37 and 51) and FaPR1. The above results can provide theoretical guidance for the molecular breeding of disease resistance of strawberry.

The construction of large-scale renewable energy sources has caused challenges to frequency stability of power system. This paper presents a method to evaluate the frequency stability of power system with high penetration of renewables. Based on input-to-state stability (ISS) theory, security/stability indices reflecting the frequency stability of the system are established. In addition, a simplified analysis method of local input-to-state stability (LISS)/ local input-to-output stability (LIOS) attributes is proposed based on System Frequency Response (SFR) model. Case studies are performed to verify the validity of the proposed method, and the corresponding security/stability indices are calculated.

The massive construction of high voltage direct current (HVDC) makes the AC/DC interactions very complicated, which seriously affects transient voltage stability. To quantify the impact of the transmission capacity on transient voltage stability, a transient voltage stability analysis method suitable for the multi-send HVDC systems is proposed. Case studies are performed under different transmission capacity, and the corresponding security/stability indices are calculated.

Abstract The toxicokinetic (TK) model‐derived kinetic bioconcentration factor (BCFk) provides a quantitatively comparable index to estimate the bioaccumulation potential of nanoparticles (NPs) that barely reach thermodynamic equilibrium in aquatic organisms, but experimental data are limited for various NPs. In the present study, a machine learning model was applied to offer reliable in silico predictions for the dynamic body burden of diverse NPs to derive corresponding parameters for the TK model. The developed eXtreme Gradient Boosting‐derived TK (XGB‐TK) model was applied to predict BCFk results for a broad range of metallic or carbonaceous NPs, with an appreciable prediction R2 of 0.96. The BCFk values were predicted based on a random combination of selected variable features, revealing that their bioaccumulation potential showed an overall negative correlation with NP density or organism size. By applying importance analysis and partial dependence plots, NP density and organism size were revealed to be the top essential features that impact the bioaccumulation potential. The conjunctively used XGB‐TK model enabled a prior comparison for diverse NPs and straightforward derivation on the dependency of features, which could also guide the bioaccumulation mechanism exploration and experimental condition formulation.

Abstract Assessing plant diversity during community succession based on plant trait and phylogenetic features within a community (alpha scale) and among communities (beta scale) could improve our understanding of community succession mechanism. However, whether changes of community functional diversity at alpha and beta scale are structured by different traits and whether integrating plant traits and phylogeny can enhance the ability in detecting diversity pattern have not been studied in detail. Thirty plots representing different successional stages were established on the Loess Plateau of China and 15 functional traits were measured for all coexisting species. We first analyzed the functional alpha and beta diversity along succession by decomposing species trait into alpha and beta components and then integrated key traits with phylogenetic information to explore their roles in shaping species turnover during community succession. We found that functional alpha diversity increased along successional stages and was structured by morphological traits, while beta diversity decreased during succession and was more structured by stoichiometry traits. Phylogenetic alpha diversity showed congruent pattern with functional alpha diversity because of phylogenetic conservation of trait alpha components (variation within community), while beta diversity showed incongruent pattern due to phylogenetic randomness of trait beta components (variation among communities). Furthermore, only integrating relatively conserved traits (plant height and seed mass) and phylogenetic information can raise the detecting ability in assessing diversity change. Overall, our results reveal the increasing niche differentiation within community and functional convergence among communities with succession process, indicating the importance of matching traits with scale in studying community functional diversity and the asymmetry of traits and phylogeny in reflecting species ecological differences under long‐term selection pressures.

Abstract. COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely ranks among the deadliest diseases in human history. As with other coronaviruses, SARS-CoV-2 infection damages not only the lungs but also the heart and many other organs that express angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV-2. COVID-19 has upended lives worldwide. Dietary behaviors have been altered such that they favor metabolic and cardiovascular complications, while patients have avoided hospital visits because of limited resources and the fear of infection, thereby increasing out-hospital mortality due to delayed diagnosis and treatment. Clinical observations show that sex, age, and race all influence the risk for SARS-CoV-2 infection, as do hypertension, obesity, and pre-existing cardiovascular conditions. Many hospitalized COVID-19 patients suffer cardiac injury, acute coronary syndromes, or cardiac arrhythmia. SARS-CoV-2 infection may lead to cardiomyocyte apoptosis and necrosis, endothelial cell damage and dysfunction, oxidative stress and reactive oxygen species production, vasoconstriction, fibrotic and thrombotic protein expression, vascular permeability and microvascular dysfunction, heart inflammatory cell accumulation and activation, and a cytokine storm. Current data indicate that COVID-19 patients with cardiovascular diseases should not discontinue many existing cardiovascular therapies such as ACE inhibitors, angiotensin receptor blockers, steroids, aspirin, statins, and PCSK9 inhibitors. This review aims to furnish a framework relating to COVID-19 and cardiovascular pathophysiology.

Abstract A numerical modeling method is proposed for the melting process of Titanium metals of Titanium alloys powder preparation used for 3D printing. The melting process simulation, which involves the tight coupling between electromagnetic field, thermal field and fluid flow as well as deformation associated during the melting process, is conducted by adopting the finite element method. A two-way coupling strategy is used to include the interactions between these fields by incorporating the material properties dependent on temperature and the coupling terms. In addition, heat radiation and phase change are also considered in this paper. The arbitrary Lagrangian–Eulerian formulation is exploited to model the deformation of Titanium metal during the melting process. The distribution of electromagnetic flux density, eddy current density, temperature, and fluid flow velocity at different time can be determined by utilizing this numerical method. In a word, the method proposed in this paper provides a general way to predict the melting process of electrode induction melting gas atomization (EIGA) dynamically, and it also could be used as a reference for the design and optimization of EIGA.

Despite intensive effort was made to regenerate injured meniscus by cell-free strategies through recruiting endogenous stem/progenitor cells, meniscus regeneration remains a great challenge in clinic. In this study, we found decellularized meniscal extracellular matrix (MECM) preserved native meniscal collagen and glycosaminoglycans which could be a good endogenous regeneration guider for stem cells. Moreover, MECM significantly promoted meniscal fibrochondrocytes viability and proliferation, increased the expression of type II collagen and proteoglycans in vitro. Meanwhile, we designed 3D-printed polycaprolactone (PCL) scaffolds which mimic the circumferential and radial collagen orientation in native meniscus. Taken these two advantages together, a micro-structure and micro-environment dually biomimetic cell-free scaffold was manipulated. This cell-free PCL-MECM scaffold displayed superior biocompatibility and yielded favorable biomechanical capacities closely to native meniscus. Strikingly, neo-menisci were regenerated within PCL-MECM scaffolds which were transplanted into knee joints underwent medial meniscectomy in rabbits and sheep models. Histological staining confirmed neo-menisci showed meniscus-like heterogeneous staining. Mankin scores showed PCL-MECM scaffold could protect articular cartilage well, and knee X-ray examination revealed same results. Knee magnetic resonance imaging (MRI) scanning also showed some neo-menisci in PCL-MECM scaffold group. In conclusion, PCL-MECM scaffold appears to optimize meniscus regeneration. This could represent a promising approach worthy of further investigation in preclinical applications.

Osteosarcoma (OS) is an aggressive tumor with a rare incidence. Extended surgical resections are the prevalent treatment for OS, which may cause critical-size bone defects. These bone defects lead to dysfunction, weakening the post-surgical quality of patients’ life. Hence, an ideal therapeutic agent for OS should simultaneously possess anti-cancer and bone repair capacities. Curcumin (CUR) has been reported in OS therapy and bone regeneration. However, it is not clear how CUR suppresses OS development. Conventionally, CUR is considered a natural antioxidant in line with its capacity to promote the nuclear translocation of a nuclear transcription factor, nuclear factor erythroid 2 (NRF2). After nuclear translocation, NRF2 can activate the transcription of some antioxidases, thereby circumventing excess reactive oxygen species (ROS) that are deleterious to cells. Intriguingly, this research demonstrated that, in vitro, 10 and 20 μM CUR increased the intracellular ROS in MG-63 cells, damaged cells’ DNA, and finally caused apoptosis of MG-63 cells, although increased NRF2 protein level and the expression of NRF2-regulated antioxidase genes were identified in those two groups.

Iodoacetic acid (IAA) is one of the most common water disinfection byproducts (DBPs). Humans and animals are widely and continuously exposed to it. Many species of water DBPs are harmful to the reproductive system of organisms. Nevertheless, the potential effects of IAA exposure on testosterone and spermatogenesis in vivo remain ambiguous. Spermatogenous cells are the site of spermatogenesis, Leydig cells are the site of testosterone synthesis, and Sertoli cells build the blood–testis barrier (BTB), providing a stable environment for the aforementioned important physiological functions in testicular tissue. Therefore, we observed the effects of IAA on spermatogenic cells, Leydig cells, and Sertoli cells in the testis. In this study, we found that oral administration of IAA (35 mg/kg body weight per day for 28 days) in male mice increased serum LH levels and reduced sperm motility, affecting average path velocity and straight line velocity of sperm. In addition, IAA promoted the expression of γH2AX, a marker for DNA double-strand breaks. Moreover, IAA downregulated the protein expression of the scavenger receptor class B type 1 (SRB1), and decreased lipid droplet transport into Leydig cells, which reduced the storage of testosterone synthesis raw materials and might cause a drop in testosterone production. Furthermore, IAA did not affect the function of BTB. Thus, our results indicated that IAA exposure affected spermatogenesis and testosterone synthesis by inducing DNA damage and reducing lipid droplet transport.

Background Immune microenvironment is well recognized as a critical regulator across cancer types, despite its complex roles in different disease conditions. Intrahepatic cholangiocarcinoma (iCCA) is characterized by a tumor-reactive milieu, emphasizing a deep insight into its immunogenomic profile to provide prognostic and therapeutic implications.Methods We performed genomic, transcriptomic, and proteomic characterization of 255 paired iCCA and adjacent liver tissues. We validated our findings through H&E staining (n=177), multiplex immunostaining (n=188), single-cell RNA sequencing (scRNA-seq) (n=10), in vitro functional studies, and in vivo transposon-based mouse models.Results Integrated multimodule data identified three immune subgroups with distinct clinical, genetic, and molecular features, designated as IG1 (immune-suppressive, 25.1%), IG2 (immune-exclusion, 42.7%), and IG3 (immune-activated, 32.2%). IG1 was characterized by excessive infiltration of neutrophils and immature dendritic cells (DCs). The hallmark of IG2 was the relatively higher tumor-proliferative activity and tumor purity. IG3 exhibited an enrichment of adaptive immune cells, natural killer cells, and activated DCs. These immune subgroups were significantly associated with prognosis and validated in two independent cohorts. Tumors with KRAS mutations were enriched in IG1 and associated with myeloid inflammation-dominated immunosuppression. Although tumor mutation burden was relatively higher in IG2, loss of heterozygosity in human leucocyte antigen and defects in antigen presentation undermined the recognition of neoantigens, contributing to immune-exclusion behavior. Pathological analysis confirmed that tumor-infiltrating lymphocytes and tertiary lymphoid structures were both predominant in IG3. Hepatitis B virus (HBV)-related samples tended to be under-represented in IG1, and scRNA-seq analyses implied that HBV infection indeed alleviated myeloid inflammation and reinvigorated antitumor immunity.Conclusions Our study elucidates that the immunogenomic traits of iCCA are intrinsically heterogeneous among patients, posing great challenge and opportunity for the application of personalized immunotherapy.

The alloying elements play an important role in the strengthening of lead tin bronze alloy and steel. Similarly, the same is true in γ-Fe (110)/Cu (110) interface. In this investigation, the effect of Ni, Sn, and P alloying atoms on the adhesion electronic properties of γ-Fe (110)/Cu (110) heterogeneous interface were simulated by using first principle method. The bonding ability of γ-Fe (110)/Cu (110) doped interface and their influence on adhesion electronic properties of the interfaces was analyzed, it is found that Ni and P atoms ware apt to doped at the interface Cu slab in the γ-Fe (110)/Cu (110)-HCP interface, and the difficulty of atomic doping from easy to difficult was ranked as: P > Ni. However, the doping of Sn atoms was not conducive to the stability and bonding of γ-Fe (110)/Cu (110) - BT interface. Besides, The P atom and Ni atom doped interface shows covalent and metallic bond characteristic respectively, which improved the stability and adhesion of the interface. However, Sn atom doped interface hardly transfer the interfacial charge, which lead to the decrease of the bonding performance and the stability of interface.

Exposure to particulate matter (PM)2.5 in air pollution is a serious health issue worldwide. At present, effective prevention measures and modalities of treatment for PM2.5-caused lung toxicity are lacking. This study elucidated the protective effect of astragaloside IV (Ast), a natural product from Astragalus membranaceous Bunge, against PM2.5-caused lung toxicity and its possible molecular mechanisms. The mice model of lung toxicity was performed by intratracheal instillation of PM2.5 dust suspension. The investigation was performed with Ast or in combination with nigericin, which is a NOD-like receptor protein 3 (NLRP3) activator. The results revealed that PM2.5 lead significant lung inflammation and promoted the pyroptosis pattern of cell death by upregulating pro-inflammatory cytokines and causing oxidative stress related to the NLRP3 inflammasome-mediated pyroptosis pathway. Ast protected against PM2.5 resulted lung toxicity via suppressing NLRP3 inflammasome‐mediated pyroptosis via NLRP3/caspase-1 axis inhibition, thereby protecting the lung against PM2.5-induced lung inflammation and oxidative damage, eventually resulting in prolonged survival in mice. Nigericin partially reversed the protective effects of Ast. The present research provides new insights into the therapeutic potential of Ast, demonstrating that it might be a possible candidate for the prevention of PM2.5-caused respiratory diseases. Targeting the NLRP3 inflammasome might be a novel therapeutic tactic for PM2.5-caused respiratory diseases.

Abstract Dynamically updated and fine‐grained flooding maps are critical for situational awareness and decision support. However, traditional methods, such as eyewitness reports, remote sensing, and hydrology models, may fail to correspond with the rapidly changing urban hydrological environment. The presence of crowdsourced data (such as social media data) allows for timely and cost‐effective monitoring of flood hazards through collective observations; however, such data can be unreliable due to sample bias and low spatiotemporal resolution. Therefore, new measures to identify flood‐affected roads are desirable. In this study, we propose a methodology that leverages taxi GPS data to support post‐event flood mapping for the road network. This method can identify whether a significant reduction in the taxi passing rate for a road segment was related to precipitation, and automatically recognize the flood‐affected roads based on a logistic regression model. Using taxi GPS data in Shenzhen as an example, we derived the flood map of the road networks, and compared and validated the results. This study demonstrated the usefulness of taxi GPS data in generating high‐quality flood maps and the value of incorporating multiple data sources for sensing near real‐time flood in the city.

Background and AimFew non-invasive models were established to identify patients with non-alcoholic steatohepatitis (NASH). Liver biopsy remains the gold standard in the clinic. Decreased serum ceruloplasmin (CP) is reported in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to develop a non-invasive model incorporating CP for identifying NASH from NAFLD without type 2 diabetes mellitus (T2DM).MethodsA total of 138 biopsy-proven patients with NAFLD without T2DM were enrolled. The CP ratio was calculated for standardization as the CP value divided by the lower limit of normal. The clinical, anthropometric, biochemical, and histological parameters were compared between the low and high CP ratio groups divided by the median value. Multivariate logistic regression analysis was performed to develop a model for identifying NASH in patients with NAFLD.ResultsThe medians of the high (n = 69) and low (n = 69) CP ratio groups were 1.43 (1.28–1.61) and 1.03 (0.94–1.12), respectively. A comparison of the two groups showed that the severity of steatosis, hepatocellular ballooning, inflammation activity, fibrosis, and liver iron deposition decreased along with the CP ratio (p < 0.05). The median CP ratio of patients with NASH was significantly lower than those with NAFL [1.15 (1.01–1.41) vs. 1.33 (1.24–1.54), p = 0.001]. A novel model which consists of the CP ratio, BMI, and aspartate aminotransferase (AST) was developed. The AUCs of the model in discriminating NASH from NAFLD was 0.796 (0.694–0.899) and 0.849 (0.713–0.984) in the training and validation groups, and 0.836 (0.659–1.000), 0.833 (0.705–0.962), and 0.821 (0.612–1.000) in patients with normal serum alanine aminotransferase, AST, and both levels, respectively.ConclusionsDecreased CP ratio is associated with more severe histological activity, a diagnosis of NASH, and hepatic iron deposition among patients with NAFLD without T2DM. The CP ratio model could be served as a non-invasive approach to identifying patients with NASH, which might reduce the need for liver biopsy.

Abstract Background Increasing evidence supports a relationship between obesity and either infertility or subfertility in women. Most previous omics studies were focused on determining if the serum and follicular fluid expression profiles of subjects afflicted with both obesity-related infertility and polycystic ovary syndrome (PCOS) are different than those in normal healthy controls. As granulosa cells (GCs) are essential for oocyte development and fertility, we determined here if the protein expression profiles in the GCs from obese subjects are different than those in their normal-weight counterpart. Methods GC samples were collected from obese female subjects (n = 14) and normal-weight female subjects (n = 12) who were infertile and underwent in vitro fertilization (IVF) treatment due to tubal pathology. A quantitative approach including tandem mass tag labeling and liquid chromatography tandem mass spectrometry (TMT) was employed to identify differentially expressed proteins. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were then conducted to interrogate the functions and pathways of identified proteins. Clinical, hormonal, and biochemical parameters were also analyzed in both groups. Results A total of 228 differentially expressed proteins were noted, including 138 that were upregulated whereas 90 others were downregulated. Significant pathways and GO terms associated with protein expression changes were also identified, especially within the mitochondrial electron transport chain. The levels of free fatty acids in both the serum and follicular fluid of obese subjects were significantly higher than those in matched normal-weight subjects. Conclusions In GCs obtained from obese subjects, their mitochondria were damaged and the endoplasmic reticulum stress response was accompanied by dysregulated hormonal synthesis whereas none of these changes occurred in normal-weight subjects. These alterations may be related to the high FFA and TG levels detected in human follicular fluid.

Abstract First principle calculations were performed to investigate the structural, mechanical, electronic properties, and thermodynamic properties of three binary Mg–B compounds under pressure, by using the first principle method. The results implied that the structural parameters and the mechanical properties of the Mg–B compounds without pressure are well matched with the obtainable theoretically simulated values and experimental data. The obtained pressure–volume and energy–volume revealed that the three Mg–B compounds were mechanically stable, and the volume variation decreases with an increase in the boron content. The shear and volume deformation resistance indicated that the elastic constant Cij and bulk modulus B increased when the pressure increased up to 40 GPa, and that MgB7 had the strongest capacity to resist shear and volume deformation at zero pressure, which indicated the highest hardness. Meanwhile, MgB4 exhibited a ductility transformation behaviour at 30 GPa, and MgB2 and MgB7 displayed a brittle nature under all the considered pressure conditions. The anisotropy of the three Mg–B compounds under pressure were arranged as follows: MgB4 > MgB2 > MgB7. Moreover, the total density of states varied slightly and decreased with an increase in the pressure. The Debye temperature ΘD of the Mg–B compounds gradually increased with an increase in the pressure and the boron content. The temperature and pressure dependence of the heat capacity and the thermal expansion coefficient α were both obtained on the basis of Debye model under increased pressure from 0 to 40 GPa and increased temperatures. This paper brings a convenient understanding of the magnesium–boron alloys.

Antibiotics are essential for treating neonatal sepsis, but abuse or inappropriate use of antibiotics have harmful adverse effects. The inappropriate use of antibiotics has led to the significant increase in bacterial antimicrobial resistance in the neonatal intensive care unit (NICU). The aim of this study was to retrospectively analyze the changes in antibiotic usages in a NICU after the implementation of an antibiotic stewardship program and to determine the impact of this implementation on the short-term clinical outcomes of very low birth weight (VLBW) infants. The antibiotic stewardship program was initiated in the NICU in early 2015. For analysis, all eligible VLBW infants born from 1 January 2014 to 31 December 2016 were enrolled, and we classified the year 2014 as pre-stewardship, 2015 as during stewardship, and 2016 as post-stewardship. A total of 249 VLBW infants, including 96 cases in the 2014 group, 77 cases in the 2015 group, and 76 cases in the 2016 group, were included for final analysis. Empirical antibiotics were used in over 90% of VLBW infants in all three groups during their NICU stay. Over the 3-year period, the duration of an initial antibiotic course was significantly reduced. The proportion of patients receiving an initial antibiotic course for ≤3 days gradually increased (2.1% vs. 9.1% vs. 38.2%, p < 0.001), while the proportion of babies treated with an initial antibiotic course >7 days significantly decreased (95.8% vs. 79.2% vs. 39.5%, p < 0.001). The total days of antibiotic usage during the entire NICU stay also showed a significant reduction (27.0 vs. 21.0 vs. 10.0, p < 0.001). After adjusting for confounders, the reduction in antibiotic usage was associated with decreased odds of having an adverse composite short-term outcome (aOR = 5.148, 95% CI: 1.598 to 16.583, p = 0.006). To assess the continuity of antibiotic stewardship in the NICU, data from 2021 were also analyzed and compared to 2016. The median duration of an initial antibiotic course further decreased from 5.0 days in 2016 to 4.0 days in 2021 (p < 0.001). The proportion of an initial antibiotic course in which antibiotics were used for ≤3 days increased (38.2% vs. 56.7%, p = 0.022). Total antibiotic usage days during the entire NICU stay also decreased from 10.0 days in 2016 to 7.0 days in 2021 (p = 0.010). The finding of this study strongly suggests that restricting antibiotic use in VLBW infants is beneficial and can be achieved safely and effectively in China.

Few non-invasive models were established for precisely identifying the immune tolerant (IT) phase from chronic hepatitis B (CHB). This study aimed to develop a novel approach that combined next-generation sequencing (NGS) and machine learning algorithms using our recently published viral quasispecies (QS) analysis package. 290 HBeAg positive patients from whom liver biopsies were taken were enrolled and divided into a training group (n = 148) and a validation group (n = 142). HBV DNA was extracted and QS sequences were obtained by NGS. Hierarchical clustering analysis (HCA) and principal component analysis (PCA) based on viral operational taxonomic units (OTUs) were performed to explore the correlations among QS and clinical phenotypes. Three machine learning algorithms, including K-nearest neighbour, support vector machine, and random forest algorithm, were used to construct diagnostic models for IT phase classification. Based on histopathology, 90 IT patients and 200 CHB patients were diagnosed. HBsAg titres for IT patients were higher than those of CHB patients (p

Objective: To explore immune-related feature genes in patients with dilated cardiomyopathy (DCM).Methods: Expression profiles from three datasets (GSE1145, GSE21610 and GSE21819) of human cardiac tissues of DCM and healthy controls were downloaded from the GEO database. After data preprocessing, differentially expressed genes (DEGs) were identified by the ‘limma’ package in R software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were then performed to identify biological functions of the DEGs. The compositional patterns of stromal and immune cells were estimated using xCell. Hub genes and functional modules were identified based on protein-protein interaction (PPI) network analysis by STRING webtool and Cytoscape application. Correlation analysis was performed between immune cell subtypes and hub genes. Hub genes with |correlation coefficient| > 0.5 and p value

Intrauterine hypoxia is a common complication during pregnancy and could increase the risk of cardiovascular disease in offspring. However, the underlying mechanism is controversial. Memantine, an NMDA receptor antagonist, is reported to be a potential cardio-protective agent. We hypothesized that antenatal memantine treatment could prevent heart injury in neonatal offspring exposed to intrauterine hypoxia. Pregnant rats were exposed to gestational hypoxia or antenatal memantine treatment during late pregnancy. Newborns were then sacrificed to assess multiple parameters. The results revealed that Intrauterine hypoxia resulted in declining birth weight, heart weight, and an abnormally high heart weight/birth weight ratio. Furthermore, intrauterine hypoxia caused mitochondrial structural, functional abnormalities and decreased expression of DRP1, and upregulation of NMDAR1 in vivo. Antenatal memantine treatment,an NMDARs antagonist, improved these changes. In vitro, hypoxia increased the glutamate concentration and expression of NMDAR1. NMDAR activation may lead to similar changes in mitochondrial function, structure, and downregulation of DRP1 in vitro. Pharmacological blockade of NMDARs by the non-competitive NMDA antagonist MK-801 or knockdown of the glutamate receptor NR1 significantly attenuated the increased mitochondrial reactive oxygen species and calcium overload-induced by hypoxia exposure. These facts suggest that memantine could provide a novel and promising treatment for clinical use in intrauterine hypoxia during pregnancy to protect the cardiac mitochondrial function in the offspring. To our best knowledge, our research is the first study that shows intrauterine hypoxia can excessively activate cardiac NMDARs and thus cause mitochondrial dysfunction.

Abstract Background Although metabolic associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide, the exact molecular mechanism of MAFLD progression remains unknown. In the present study, Tandem Mass Tag-labeled quantitative proteomic technology was used to elucidate the protein expression patterns of liver tissues in the progression of MAFLD, providing new potential therapeutic targets of it. Methods Five 6-week-old male C57BL/6 mice were fed with high fat diet (HFD) for 22 weeks to establish the MAFLD mouse models. Five C57BL/6 mice of the same age were fed with normal diet (ND) and taken as controls. Mice serum were sampled for biochemical tests, and livers were isolated for histopathological examinations. Six mouse liver samples (three from each group) were performed for proteomic analysis. Differentially expressed proteins were defined using fold change of > 1.5 or

Abstract Background Extended exposure to high concentrations of PM2.5 changes the human microbiota profile, which in turn may increase morbidity and mortality due to respiratory system damage. A balanced microecosystem is crucial to human health, and certain health-related problems may be addressed by effective microecosystem regulation. Recent studies have confirmed that probiotics may reduce the incidence of respiratory diseases. However, few studies have investigated probiotic treatment outcomes in subjects exposed to high concentrations of PM2.5. Methods This study is designed as a prospective, randomized, participants- and assessor-blinded, placebo-controlled trial. One hundred and twenty eligible volunteers recruited from October 2019 to July 2020 in downtown Chengdu, China, will be treated with either probiotics or placebo over 4 consecutive weeks. The primary outcome will be 16SrRNA sequencing assay data from nasal and intestinal secretions. Secondary outcomes will be pulmonary function, score on a gastrointestinal symptom rating scale, COOP/WONCA charts, and the Short-Form Health Survey 36 for quality of life. Results will be analyzed to assess differences in clinical efficacy between groups. Six-month follow-up examinations will evaluate the long-term value of probiotics on cardiovascular and respiratory disease end-point events. Discussion We will explore the characteristics of nasal and intestinal microbiota in a population with high exposure to PM2.5. Probiotics and placebo interventions will be tested for efficacy in microbial balance regulation, effects on lung and physical functions, and quality of life improvement. This study is expected to provide reliable evidence to support the widespread promotion of probiotics in clinical practice for the protection of individuals with high exposure to PM2.5. Trial registration Chinese Clinical Trial Registry ChiCTR1900025469 . Registered on 27 August 2019.

Abstract Background A virus community is the spectrum of viral strains populating an infected host, which plays a key role in pathogenesis and therapy response in viral infectious diseases. However automatic and dedicated pipeline for interpreting virus community sequencing data has not been developed yet. Results We developed Quasispecies Analysis Package (QAP), an integrated software platform to address the problems associated with making biological interpretations from massive viral population sequencing data. QAP provides quantitative insight into virus ecology by first introducing the definition “virus OTU” and supports a wide range of viral community analyses and results visualizations. Various forms of QAP were developed in consideration of broader users, including a command line, a graphical user interface and a web server. Utilities of QAP were thoroughly evaluated with high-throughput sequencing data from hepatitis B virus, hepatitis C virus, influenza virus and human immunodeficiency virus, and the results showed highly accurate viral quasispecies characteristics related to biological phenotypes. Conclusions QAP provides a complete solution for virus community high throughput sequencing data analysis, and it would facilitate the easy analysis of virus quasispecies in clinical applications.

Abstract Background The dedifferentiation of chondrocytes and the unstable chondrogenic differentiation status of pluripotent mesenchymal stem cells (MSCs) are immense issues in cell-based articular cartilage repair and regenerative strategies. Here, to improve the cartilage characteristics of seed cells, a double biomimetic acellular cartilage extracellular matrix (ACECM)-oriented scaffold was used to mimic the cartilage microenvironment for human umbilical cord Wharton’s jelly-derived MSCs (hWJMSCs) and primary cartilage cells (pACs) to regenerate hyaline cartilage. Methods A double biomimetic ACECM-oriented scaffold was created from the cartilage extracellular matrix of pig articular cartilage using pulverization decellularization freeze-drying procedures. hWJMSCs and pACs were co-cultured at ratios of 50:50 (co-culture group, ACCC), 0:100 (ACAC group) and 100:0 (ACWJ group) in the ACECM-oriented scaffold, and the co-culture system was implanted in a caprine model for 6 months or 9 months to repair full-thickness articular cartilage defects. The control groups, which had no cells, comprised the blank control (BC) group and the ACECM-oriented scaffold (AC) group. Gross morphology and magnetic resonance imaging (MRI) as well as histological and biomechanical evaluations were used to characterize the cartilage of the repair area. Results Relative to the control groups, both the gross morphology and histological staining results demonstrated that the neotissue of the ACCC group was more similar to native cartilage and better integrated with the surrounding tissue. Measurements of glycosaminoglycan content and Young’s modulus showed that the repair areas had more abundant cartilage-specific content and significantly higher mechanical strength in the ACCC group than in the control groups, especially at 9 months. On MRI, the T2-weighted signal of the repair area was homogeneous, and the oedema signal disappeared almost completely in the ACCC group at 9 months. HLA-ABC immunofluorescence staining demonstrated that hWJMSCs participated in the repair and regeneration of articular cartilage and escaped surveillance and clearance by the caprine immune system. Conclusion The structure and components of double biomimetic ACECM-oriented scaffolds provided a cartilage-like microenvironment for co-cultured seed cells and enhanced the biomechanics and compositions of neotissue. This co-culture system has the potential to overcome the dedifferentiation of passage chondrocytes and the unstable chondrogenic differentiation status of MSCs.

The amino acid/auxin permease (AAAP) gene family plays a significant role in the long-distance amino acid transport and is involved in plant stress responses and various developmental processes. The functions of the AAAP family have been extensively discussed in multiple organisms, whereas detailed information of this family in strawberry (Fragaria vesca) has not been reported yet. In this study, we identified 45 AAAP genes in the strawberry genome. Phylogenetic analysis indicated that AAAPs from strawberry and Arabidopsis were clustered into eight groups. Expression analysis of the AAAP family showed that AAAP genes were expressed differentially in different developmental stages of flower and fruit, and were significantly induced after Colletotrichum gloeosporioides infection. Our study provides a comprehensive understanding of the strawberry AAAP family and demonstrates their potential roles in disease resistance, providing more reference for further research.

Ionospheric clutter is a major factor affecting the performance of high-frequency surface wave radar (HFSWR). Previous studies have been mainly focused on the development of ionospheric clutter suppression methods involving delicate signal processing techniques or additional antennas. However, ionospheric clutter originates from the interaction between HF waves and the ionosphere, thus it contains the characteristics of the latter. Therefore, ionospheric clutter can be analyzed to obtain the parameters of the reflecting ionosphere, expanding the value of HFSWR. This article presents the preliminary coordinated observation and analysis results of the characteristics of the ionosphere at mid-latitudes of China using both HFSWR and ionosonde. The results demonstrate the existence of an oblique skywave propagation path (0.5 jump, 1 jump, etc.) in addition to the vertical reflection path and ionosphere-ocean mixed path. HFSWR beams were also found split into an O-trace and an X-trace after entering the ionosphere. Furthermore, range-folded ionospheric echoes are related to the short-term thickening of the F2-layer, showing strong fluctuation in the range-Doppler spectrum of HFSWR. These observed characteristics of ionospheric echoes are useful for the development of an efficient ionospheric clutter suppression algorithm for HFSWR and further investigation of the ionospheric mechanisms at mid-latitudes.

Hexagonal crystal MgAlB _4 is a strengthening phase in Al matrix composites, which can significantly improve ultimate tensile strength. In this paper, the surface perform, interfacial bonding characteristic, fracture mechanism, and electronic properties of the Al(111)/MgAlB _4 (0001) interface were thoroughly investigated by the first principles method. The results reveal that the top-site and bridge-site configurations were more unstable than the hollow-site. Besides, from the calculated results of interfacial energy and work of adhesion, the hollow-stacked Al(111)/B(Al)-terminated/MgAlB _4 (0001) interface expresses stronger stability than other interfacial models, which is attributable to the higher work of adhesion and lower interfacial energy of the hollow-stacked Al(111)/B(Al)-terminated/MgAlB _4 (0001) interface. Analysis of electronic structure reveals that the Al-termination and Mg-termination Al(111)/MgAlB _4 (0001) interface presents Al-Al and Al-Mg metallic bonds at the interface, respectively, but the B(Al)-termination Al(111)/MgAlB _4 (0001) interface expresses strong Al-B covalent bonds characteristic, which leads to the highest interface stability. The results of tensile fracture revealed that the HCP stacked B(Al)-termination interface transferred the external stress to Al bulk, due to the Al-B covalent bond formed near the interface. Therefore, ceramic phase MgAlB _4 can effectively promote the particle reinforcement of Al matrix composites.

Osteosarcoma (OS), a primary malignant bone tumor, stems from bone marrow-derived mesenchymal stem cells (BMSCs) and/or committed osteoblast precursors. Distant metastases, in particular pulmonary and skeletal metastases, are common in patients with OS. Moreover, extensive resection of the primary tumor and bone metastases usually leads to bone defects in these patients. Bone morphogenic protein-2 (BMP-2) has been widely applied in bone regeneration with the rationale that BMP-2 promotes osteoblastic differentiation of BMSCs. Thus, BMP-2 might be useful after OS resection to repair bone defects. However, the potential tumorigenicity of BMP-2 remains a concern that has impeded the administration of BMP-2 in patients with OS and in populations susceptible to OS with severe bone deficiency (e.g., in patients with genetic mutation diseases and aberrant activities of bone metabolism). In fact, some studies have drawn the opposite conclusion about the effect of BMP-2 on OS progression. Given the roles of BMSCs in the origination of OS and osteogenesis, we hypothesized that the responses of BMSCs to BMP-2 in the tumor milieu may be responsible for OS development. This review focuses on the relationship among BMSCs, BMP-2, and OS cells; a better understanding of this relationship may elucidate the accurate mechanisms of actions of BMP-2 in osteosarcomagenesis and thereby pave the way for clinically safer and broader administration of BMP-2 in the future. For example, a low dosage of and a slow-release delivery strategy for BMP-2 are potential topics for exploration to treat OS.