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Background: Modular organization reflects the activity patterns of our brain. Different disease states may lead to different activity patterns and clinical features. Early onset depression (EOD) and late onset depression (LOD) share the same clinical symptoms, but have different treatment strategies and prognosis. Thus, explored the modular organization of EOD and LOD might help us understand their pathogenesis.Method: The study included 82 patients with late life depression (EOD 40, LOD 42) and 90 healthy controls. We evaluated the memory, executive function and processing speed and performed resting-stage functional MRI for all participants. We constructed a functional network based on Granger causality analysis and carried out modularity, normalized mutual information (NMI), Phi coefficient, within module degree z-score, and participation coefficient analyses for all the participants.Result: The Granger function network analysis suggested that the functional modularity was different among the three groups (Pauc = 0.0300), and NMI analysis confirmed that the partition of EOD was different from that of LOD (Pauc = 0.0190). Rh.10d.ROI (polar frontal cortex) and Rh.IPS1.ROI (dorsal stream visual cortex) were shown to be the potential specific nodes in the modular assignment according to the Phi coefficient (P = 0.0002, Pfdr = 0.0744 & P = 0.0004, Pfdr = 0.0744).Conclusion: This study reveal that the functional modularity and partition were different between EOD and LOD in Granger function network. These findings support the hypothesis that different pathological changes might exist in EOD and LOD.

Summary: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into an unprecedented global pandemic. Nucleoside analogs, such as Remdesivir and Favipiravir, can serve as the first-line broad-spectrum antiviral drugs by targeting the viral polymerases. However, the underlying mechanisms for the antiviral efficacies of these drugs are far from well understood. Here, we reveal that Favipiravir, as a pyrazine derivative, could be incorporated into the viral RNA products by mimicking both adenine and guanine nucleotides. This drug thus inhibits viral replication mainly by inducing mutations in progeny RNAs, different from Remdesivir or other RNA-terminating nucleoside analogs that impair the elongation of RNA products. We further determined the cryo-EM structure of Favipiravir bound to the replicating polymerase complex of SARS-CoV-2 in the pre-catalytic state. This structure provides a missing snapshot for visualizing the catalysis dynamics of coronavirus polymerase, and reveals an unexpected base-pairing pattern between Favipiravir and pyrimidine residues that may explain its capacity for mimicking both adenine and guanine nucleotides. These findings shed light on the mechanism of coronavirus polymerase catalysis and provide a rational basis for developing antiviral drugs to combat the SARS-CoV-2 pandemic.

Robot detection, recognition, positioning, and other applications require not only real-time video image information but also the distance from the target to the camera, that is, depth information. This paper proposes a method to automatically generate any monocular camera depth map based on RealSense camera data. By using this method, any current single-camera detection system can be upgraded online. Without changing the original system, the depth information of the original monocular camera can be obtained simply, and the transition from 2D detection to 3D detection can be realized. In order to verify the effectiveness of the proposed method, a hardware system was constructed using the Micro-vision RS-A14K-GC8 industrial camera and the Intel RealSense D415 depth camera, and the depth map fitting algorithm proposed in this paper was used to test the system. The results show that, except for a few depth-missing areas, the results of other areas with depth are still good, which can basically describe the distance difference between the target and the camera. In addition, in order to verify the scalability of the method, a new hardware system was constructed with different cameras, and images were collected in a complex farmland environment. The generated depth map was good, which could basically describe the distance difference between the target and the camera.

BackgroundOur previous study in animal models revealed that bilirubin could induce Aβ formation and deposition. Bilirubin may be important in neurodegenerative dementia with Aβ deposition. Hence, lowering the concentration of the free bilirubin capable of crossing the blood brain–barrier may benefit the treatment of Alzheimer’s disease (AD).ObjectivesThe objectives of this study were to examine the change in the serum bilirubin and albumin concentrations of dementia patients with Aβ deposition, and to determine the effects of intravenous administration of albumin in the treatment of AD.MethodsBilirubin and albumin concentrations in dementia patients with Aβ deposition were examined. Cell viability and apoptosis were determined in dopaminergic neuron-like cells MN9D treated with bilirubin in the presence of diverse concentrations of serum. Human albumin at a dose of 10 g every 2 weeks for 24 weeks was administered intravenously to AD patients to examine the effect of albumin on AD symptoms.ResultsSignificantly higher indirect bilirubin (IBIL) concentrations, lower albumin concentrations, and higher ratio of IBIL to albumin (IBIL/ALB) were observed in dementia patients with Aβ deposition, including AD, dementia with Lewy bodies, and general paresis of insane. In vitro assays showed that bilirubin-induced injury in cultured dopaminergic neuron-like cells negatively depends on the concentration of serum in the culture medium. General linear model with repeated measures analysis indicated a main effect of group on the change in albumin concentrations and Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL) scores, and the main effect of time and group, and group-by-time interaction on the change of Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB) scores. Analysis of the combined data of the entire 28 weeks of assessment period using the area under curve convincingly showed significantly improvements in the change of albumin concentrations, ADCS-ADL scores, and CDR-SB scores.ConclusionIBIL and the IBIL/ALB ratio are significantly higher in dementia patients with Aβ deposition, and intravenous administration of albumin is beneficial to AD treatment.Trial RegistrationThe intervention study was registered at http://www.chictr.org.cn (ChiCTR-IOR-17011539). Date of registration: June 1, 2017.

The long-term stability of perovskite solar cells (PSCs) remains an issue impeding their commercialization. Generally, polycrystalline perovskite thin films have many defects on the grain boundaries, which affect the optoelectronic performance and stability of the devices under moisture, heat, illumination, and the presence of an electric field condition. The O-donor Lewis base is often employed to regulate the performance of PSCs such as carbonyl and carboxyl compounds. Herein, we have developed a concept of radical molecular modulation using the O-donor group for high-performance perovskite photovoltaic devices. The judiciously designed radical modulators 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), which located at the perovskite grain boundary through interaction with the perovskite surface sites, effectively passivated the surface defects while templating the formation of large grain crystal and high-quality perovskite thin films. Accordingly, the optimized TEMPO-modulated PSCs achieved a power conversion efficiency of 20.73% with superior stability. This work makes an important contribution for exploring the effect of radical in perovskites to improve the performance of PSCs and other optoelectronic devices.

Summary: The ongoing global pandemic of coronavirus disease 2019 (COVID-19) has caused a huge number of human deaths. Currently, there are no specific drugs or vaccines available for this virus (SARS-CoV-2). The viral polymerase is a promising antiviral target. Here, we describe the near-atomic-resolution structure of the SARS-CoV-2 polymerase complex consisting of the nsp12 catalytic subunit and nsp7-nsp8 cofactors. This structure highly resembles the counterpart of SARS-CoV with conserved motifs for all viral RNA-dependent RNA polymerases and suggests a mechanism of activation by cofactors. Biochemical studies reveal reduced activity of the core polymerase complex and lower thermostability of individual subunits of SARS-CoV-2 compared with SARS-CoV. These findings provide important insights into RNA synthesis by coronavirus polymerase and indicate adaptation of SARS-CoV-2 toward humans with a relatively lower body temperature than the natural bat hosts.

Selenium (Se) is a beneficial element to plants and an essential element to humans. Colonization by arbuscular mycorrhizal fungi (AMF) and supply of phosphorus (P) fertilizer may affect the bioavailability of Se in soils and the absorption of Se by plants. To investigate the interaction between AMF and P fertilizer on the transformation of soil Se fractions and the availability of Se in the rhizosphere of alfalfa, we conducted a pot experiment to grow alfalfa in a loessial soil with three P levels (0, 5, and 20 mg kg-1) and two mycorrhizal inoculation treatments (without mycorrhizal inoculation [−AMF] and with mycorrhizal inoculation [+AMF]), and the interaction between the two factors was estimated with two-way ANOVA. The soil in all pots was supplied with Se (Na2SeO3) at 1 mg kg-1. In our results, shoot Se concentration decreased, but plant Se content increased significantly as P level increased and had a significant positive correlation with AMF colonization rate. The amount of total carboxylates in the rhizosphere was strongly affected by AMF. The amounts of rhizosphere carboxylates and alkaline phosphatase activity in the +AMF and 0P treatments were significantly higher than those in other treatments. The concentration of exchangeable-Se in rhizosphere soil had a positive correlation with carboxylates. We speculated that rhizosphere carboxylates promoted the transformation of stable Se (iron oxide-bound Se) into available Se forms, i.e. exchangeable Se and soluble Se. Colonization by AMF and low P availability stimulated alfalfa roots to release more carboxylates and alkaline phosphatase. AMF and P fertilizer affected the transformation of soil Se fractions in the rhizosphere of alfalfa.

Heavy metals have caused serious environmental issues, which are enriched during open-cast coal mining. It is urgent to develop sustainable remediation materials to protect and restore the contaminated soil and aquifers in mining areas. The feasibility of applying Pisha sandstone (PS) and Na+-modified Pisha sandstone (Na-PS) for adsorption of heavy metals was evaluated. Na-PS exhibited maximum Cd(II) and Cu(II) removal rates of 65.9% and 99.8%, respectively, exceeding the corresponding values for PS (8.2% and 1.3%, respectively) in 1 × 10−3 M solution. Efficient heavy metals adsorption occurred in the pH range 5.0–6.0. The adsorption of Cu(II) and Cd(II) on PS and Na-PS was characterized by kinetic models and adsorption isotherms and was well represented by pseudo-second-order kinetics (R2 > 0.99) and the Langmuir and Freundlich isotherm models. The values of the thermodynamic parameters indicated that the interactions were spontaneous endothermic reactions. Binary solutions adsorption isotherms indicated that the linearity of the adsorption amount and initial concentration of Cu(II) and Cd(II) was better in certain ranges and the adsorbents were selective towards Cu(II) rather than Cd(II). Therefore, PSs can be used as excellent adsorbents for Cu(II) and Cd(II) remediation from contaminated surface water.

(1) Background: Odor identification (OI) dysfunction is a potential predictor of developing dementia in late life depression (LLD). However, it is not clear whether patients with early onset depression (EOD) and late onset depression (LOD) may exhibit different OI dysfunctions. The aim of this study was to compare OI between EOD patients and LOD patients and its relationship with cognitive function. (2) Methods: A total of 179 patients with LLD and 189 normal controls were recruited. Participants underwent clinical assessment, olfactory testing, and comprehensive neuropsychological assessment. The OI scores of EOD patients and LOD patients were compared, and correlation analyses and mediation analyses were used to explore the relationship between OI and cognition. (3) Result: LOD patients exhibited lower OI scores than EOD patients and normal controls (NCs). Additionally, the LOD patients exhibited a higher percentage of OI dysfunction than the EOD patients. Moreover, OI scores were associated with global cognition, memory, language, and visuospatial ability in the EOD group (p < 0.05) but were not associated with any cognitive score in the LOD patients (p > 0.05). Finally, the scores of the Auditory Verbal Learning Test Immediate recall and Boston Naming Test exhibited a partially mediating effect on the difference in OI scores between the EOD and LOD patients. (4) Conclusions: LOD patients exhibited worse OI than EOD patients, and their difference in OI was mediated by their memory and language function.

Abstract Background Genetic defects in the mitochondrial aminoacyl-tRNA synthetase are important causes of mitochondrial disorders. VARS2 is one of the genes encoding aminoacyl-tRNA synthetases. Recently, an increasing number of pathogenic variants of VARS2 have been reported. Case presentation We report the novel compound heterozygous pathogenic VARS2 mutations c.643 C > T (p. His215Tyr) and c.1354 A > G (p. Met452Val) in a female infant who presented with poor sucking at birth, poor activity, hyporeflexia, hypertonia, persistent pulmonary hypertension of newborn (PPHN), metabolic acidosis, severe lactic acidosis, expansion and hypertrophic cardiomyopathy. These heterozygous mutations were carried individually by the proband’s parents and elder sister; the two mutations segregated in the family and were the cause of the disease in the proband.The c.643 C > T (p. His215Tyr) mutation was not described in the ExaC, GNomAD and 1000 Genomes Project databases, and the frequency of c.1354 A > G (p. Met452Val) was

Keratin 76 (Krt76) is an epithelial differentiation marker that is downregulated in oral squamous cell carcinomas, correlating with poor prognosis. Here the authors show that genetic ablation of Krt76 in a mouse model results in increased susceptibility to carcinogenesis via enhanced accumulation of Tregs.

Abstract Background The fatty acid composition of B. napus’ seeds determines the oil’s nutritional and industrial values, and affects seed germination. Many studies have reported correlations among C16:0, C18:0, C18:1, C18:2 and C18:3 based on phenotypic data; however, the genetic basis of the fatty acid composition in B. napus is still not well understood. Results In this study, unconditional and conditional quantitative trail locus (QTL) mapping analyses were conducted using a recombinant inbred line in six environments. In total, 21 consensus QTLs each for C16:0, C18:0 and C18:2, 16 for C18:1 and 22 for C18:3 were detected by unconditional mapping. The QTLs with overlapping confidence intervals were integrated into 71 pleiotropically unique QTLs by meta-analysis. Two major QTLs, uuqA5–6 and uuqA5–7, simultaneously affected the fatty acids, except C18:0, in most of environments, with the homologous genes fatty acid desaturase 2 (FAD2) and glycerol-3-phosphate sn-2-acyltransferase 5 (GPAT5) occurring in the confidence interval of uuqA5–6, while phosphatidic acid phosphohydrolase 1 (PAH1) was assigned to uuqA5–7. Moreover, 49, 30, 48, 60 and 45 consensus QTLs were detected for C16:0, C18:0, C18:1, C18:2 and C18:3, respectively, by the conditional mapping analysis. In total, 128 unique QTLs were subsequently integrated from the 232 conditional consensus QTLs. A comparative analysis revealed that 63 unique QTLs could be identified by both mapping methodologies, and 65 additional unique QTLs were only identified in conditional mapping. Conclusions Thus, conditional QTL mapping for fatty acids may uncover numerous additional QTLs that were inhibited by the effects of other traits. These findings provide useful information for better understanding the genetic relationships among fatty acids at the QTL level.

Antibiotic resistance is a serious global health concern that may have significant social and financial consequences. Methicillin-resistant Staphylococcus aureus (MRSA) infection is responsible for substantial morbidity and leads to the death of 21.8% of infected patients annually. A lack of novel antibiotics has prompted the exploration of therapies targeting bacterial virulence mechanisms. The two-component signal transduction system (TCS) enables microbial cells to regulate gene expression and the subsequent metabolic processes that occur due to environmental changes. The YycFG TCS in S. aureus is essential for bacterial viability, the regulation of cell membrane metabolism, cell wall synthesis and biofilm formation. However, the role of YycFG-associated biofilm organization in S. aureus antimicrobial drug resistance and gene regulation has not been discussed in detail. We reviewed the main molecules involved in YycFG-associated cell wall biosynthesis, biofilm development and polysaccharide intercellular adhesin (PIA) accumulation. Two YycFG-associated regulatory mechanisms, accessory gene regulator (agr) and staphylococcal accessory regulator (SarA), were also discussed. We highlighted the importance of biofilm formation in the development of antimicrobial drug resistance in S. aureus infections. Data revealed that inhibition of the YycFG pathway reduced PIA production, biofilm formation and bacterial pathogenicity, which provides a potential target for the management of MRSA-induced infections.

On-orbit space technology is used for tasks such as the relative navigation of non-cooperative targets, rendezvous and docking, on-orbit assembly, and space debris removal. In particular, the pose estimation of space non-cooperative targets is a prerequisite for studying these applications. The capabilities of a single sensor are limited, making it difficult to achieve high accuracy in the measurement range. Against this backdrop, a non-cooperative target pose measurement system fused with multi-source sensors was designed in this study. First, a cross-source point cloud fusion algorithm was developed. This algorithm uses the unified and simplified expression of geometric elements in conformal geometry algebra, breaks the traditional point-to-point correspondence, and constructs matching relationships between points and spheres. Next, for the fused point cloud, we proposed a plane clustering-method-based CGA to eliminate point cloud diffusion and then reconstruct the 3D contour model. Finally, we used a twistor along with the Clohessy–Wiltshire equation to obtain the posture and other motion parameters of the non-cooperative target through the unscented Kalman filter. In both the numerical simulations and the semi-physical experiments, the proposed measurement system met the requirements for non-cooperative target measurement accuracy, and the estimation error of the angle of the rotating spindle was 30% lower than that of other, previously studied methods. The proposed cross-source point cloud fusion algorithm can achieve high registration accuracy for point clouds with different densities and small overlap rates.

Abstract A multifunctional fluorescent probe BHN-Fe3O4@SiO2 nanostructure for Fe3+ was designed and developed. It has a good selective response to Fe3+ with fluorescence quenching and can be recycled using an external magnetic field. With adding EDTA (2.5 × 10−5 M) to the consequent product Fe3+-BHN-Fe3O4@SiO2, Fe3+ can be removed from the complex, and its fluorescence probing ability recovers, which means that this constituted on-off type fluorescence probe could be reversed and reused. At the same time, the probe has been successfully applied for quantitatively detecting Fe3+ in a linear mode with a low limit of detection 1.25 × 10−8 M. Furthermore, the BHN-Fe3O4@SiO2 nanostructure probe is successfully used to detect Fe3+ in living HeLa cells, which shows its great potential in bioimaging detection.

Rapeseed is a very important oil crop in China; however, its production is challenging due to the absence of effective weed management strategies. This is predominantly because of a shortage of herbicide resistance genes. Acetohydroxyacid synthase (AHAS) herbicides inhibit AHAS, a key enzyme involved in branched-chain amino acid synthesis that is required for plant growth. A rapeseed line designated M342 with AHAS herbicide resistance was developed through seed mutagenesis and was studied to assess the level and mode of inheritance of the resistance and to identify the molecular basis of resistance. M342 possessed a high level of cross-resistance to sulfonylureas (SUs) and imidazolinones (IMIs). This resistance was due to AHAS insensitivity to these herbicides and was inherited as a dominant trait conferred by a single nuclear-encoded gene. Molecular analysis revealed the presence of a Trp574Leu mutation in M342, and an allele-specific cleaved amplified polymorphic sequence (AS-CAPS) marker was developed and cosegregated with herbicide resistance in the F2, BC1, and BC2 populations. This mutation altered the transcript levels of BnAHAS1 and BnAHAS3 in M342 compared with those in the wild type, but it did not affect the agronomic or quality traits. The simple genetic inheritance of this mutation and the availability of the cleaved amplified polymorphic sequence (CAPS) marker and herbicide resistance gene should facilitate the development of herbicide-resistant rapeseed cultivars for effective weed control in China.

Abstract Background Bacterial pathogens are a major cause of childhood community acquired lower respiratory tract infections (CA-LRTIs), and few data described the impact of antimicrobial resistance on children with CA-LRTIs. This study aims to investigate the antimicrobial resistance in common bacterial agents among hospitalized children with CA-LRTIs between 2011 and 2016 in Dongguan, China. Methods Sputum samples were collected from hospitalized children (0–5 years old) with CA-LRTIs in Dongguan Children’s Hospital. Bacterial pathogens were detected using traditional culture methods, and disc diffusion tests were used to determine antibiotic resistance. Results Among the 2360 samples analyzed, 342 (14.5%) were positive for bacterial infection. The most prevalent pathogen was MSSA (2.3%), followed by MRSA (1.5%), E. coli (1.7%), E. coli ESBLs (1.2%), K. pneumonia ESBLs (1.5%), K. pneumonia (1.4%) and S. pneumonia (1.3%). Of the hospitalized patients with bacteria causing of CA-LRTIs, 90.1% were less than 1-year-old. MSSA and MRSA were more commonly isolated in infants less than 3 months. E. coli, K. pneumonia and K. pneumonia ESBLs were more common bacteria causing CA-LRTIs in infants less than 1 month. Resistance levels to penicillins, fluoroquinolones, macrolides, cephalosporins, carbapenems and vancomycin varied in different bacteria. Conclusions S. aureus, E coli and K. pneumonia were the common bacterial isolates recovered from chidren with CA-LTRIs during 2011–2015. Age group of under 1 year old was at a high risk of bacterial infections. Many isolates showed antibiotic resistance level was associated with antibiotic usage in clinic. Increasing surveillance of antibiotic resistance is urgently needed and develops better strategies to cure the antibiotic abuse in China.

Abstract Background Porcine Deltacoronavirus (PDCoV) is a newly emerged enteropathogenic coronavirus that causes diarrhea and mortality in neonatal piglets. PDCoV has spread to many countries around the world, leading to significant economic losses in the pork industry. Therefore, a rapid and sensitive method for detection of PDCoV in clinical samples is urgently needed. Results In this study, we developed a single-tube one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay specific for nucleocapsid gene to diagnose and monitor PDCoV infections. The detection limit of RT-LAMP assay was 1 × 101 copies of PDCoV, which was approximately 100-fold more sensitive than gel-based one-step reverse transcription polymerase chain reaction (RT-PCR). This assay could specifically amplify PDCoV and had no cross amplification with porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine kobuvirus (PKoV), porcine astrovirus (PAstV), porcine reproductive and respiratory syndrome virus (PRRSV), classic swine fever virus (CSFV), and porcine circovirus type 2 (PCV2). By screening a panel of clinical specimens (N = 192), this method presented a similar sensitivity with nested RT-PCR and was 1–2 log more sensitive than conventional RT-PCR in detection of PDCoV. Conclusions The RT-LAMP assay established in this study is a potentially valuable tool, especially in low-resource laboratories and filed settings, for a rapid diagnosis, surveillance, and molecular epidemiology investigation of PDCoV infections. To the best of our knowledge, this is the first work for detection of newly emerged PDCoV with LAMP technology.

How to extract characteristic parameters from vibration signals with noise is a key problem of bearing fault diagnosis. A novel method based on Morlet wavelet-Singular Value Decomposition（ SVD） and Variable Predictive Model based Class Discriminate（ VPMCD） was proposed in this paper aiming to solve this problem. Firstly,Morlet wavelet transform was used to pre-process the signals in the time domain to obtain a time-frequency coefficient matrix,then SVD was applied to the matrix to remove noise and extract the weak fault information in the corresponding dimensions according to the singular value curvature spectrum; Secondly,the signal components near the optimal meature were selected,and the Shannon energy entropy were used as the characteristic parameters to construct the feature vectors,which were then used to establish the fault identification model based on VPMCD. Finally,5-fold cross validation method and Jackknife test method were adopted to verify the proposed method,and the results have demonstrated its effectiveness.

Bacillus thuringiensis subspecies morrisoni strain HD12, whose genome harbors multiple insecticidal protein-encoding genes, includes eight cry genes, as indicated by genome sequencing. This strain produces crystals that are toxic to lepidopteran species. These crystal inclusions were purified by sucrose gradients and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), followed by liquid chromatography-mass spectrometry, and found to contain five proteins (Cry1Da, Cry1Ae, Cry1Bb, Cry1Fb, and Cry1Ja). The transcriptional activities of the cry1Da, cry1Ae, cry1Bb, cry1Fb, and cry1Ja promoters indicated that transcription of cry1Da is controlled by SigE; however, the other four cry genes were found to be controlled by both SigE and SigK. The activities of the cry1Ja and cry1Fb promoters were the strongest among the five genes studied. These promoters were therefore used to direct the expression of the Cry1Ac- and Cry2Ab-encoding genes concurrently in a single strain. Our findings indicate that promoters with the same transcriptional profile may be used to direct the expression of different cry genes in one strain. Our results are expected to be valuable for the construction of strains with efficient expression of multiple cry genes in order to overcome current limitations associated with the application of B. thuringiensis-based insecticides.

Myeloid-derived suppressor cells (MDSCs) are a major component of the immunosuppressive tumor microenvironment (TME) and have been recognized as a contributing factor to inflammation-related cancers. However, the molecular mechanisms of MDSCs accumulation and activation remain elusive. We previously showed that the proinflammatory molecule S100A9 in TME exerts a tumor-promoting effect in colorectal carcinoma (CRC). In this report, we investigated the effect and molecular mechanisms of S100A9 on the accumulation and immunosuppressive function of MDSCs in CRC. Elevated S100A9 and MDSCs were found in tumor tissue and peripheral blood from CRC patients. Circulating S100A9 and MDSCs were positively associated to each other, and both S100A9 and MDSCs were correlated to neoplastic progression. Using a CRC cell line LoVo-induced MDSCs model, we found that S100A9 stimulated chemotaxis and activation but not viability of MDSCs. Mechanistic studies demonstrated that activation of RAGE-mediated p38 MAPK and TLR4-mediated NF-κB signaling pathways were involved in S100A9-induced chemotaxis and MDSCs activation, respectively. Furthermore, ROC analysis showed that combination detection of S100A9 and MDSCs was superior to individual detection of these two factors for diagnosing CRC patients with advanced staging and lymphatic metastasis, which yielded an area under the ROC curve (AUC) of 0.92 with 86.7% sensitivity and 86.4% specificity, and an AUC of 0.82 with 75% sensitivity and 77.1% specificity, respectively. Collectively, our study suggests that the S100A9 plays a pivotal role in immunosuppressive TME by stimulating MDSCs chemotaxis and activation, and combination detection of S100A9 and MDSCs may serve as a potential marker for diagnosis of CRC progression.

Regulatory T cells (Tregs) are a subpopulation of T cells that maintain immunological tolerance. In inflammatory responses the function of Tregs is tightly controlled by several factors including signaling through innate receptors such as Toll like receptors and anaphylatoxin receptors allowing an effective immune response to be generated. Protease-activated receptors (PARs) are another family of innate receptors expressed on multiple cell types and involved in the pathogenesis of autoimmune disorders. Whether proteases are able to directly modulate Treg function is unknown. Here, we show using two complimentary approaches that signaling through PAR-4 influences the expression of CD25, CD62L, and CD73, the suppressive capacity, and the stability of Tregs, via phosphorylation of FoxO1 and negative regulation of PTEN and FoxP3. Taken together, our results demonstrate an important role of PAR4 in tuning the function of Tregs and open the possibility of targeting PAR4 to modulate immune responses.

The present research aims to identify the main peculiar economics of professional team sports, reflect on whether they apply to esports, and derive some implications. To achieve this aim, two sequential snowballing literature reviews were conducted. First, the literature on the peculiar economics of professional team sports was reviewed and assessed by the authors, based on their degree of distinctiveness and how core they are for the sector. Second, based on the main peculiar economics identified, a similar process considering economic aspects in the esports literature was conducted. The first review enabled the identification of 50 peculiar economics of professional team sports, of which 12 were assessed as the most distinctive and core to the sector. These 12 main peculiar economics were then considered in relation to the esports literature. This second review enabled the identification of some economic similarities and differences between sports and esports, before deriving some implications.

To date, two genotypes, i.e., genotype 1 (G1) and genotype 2 (G2), of porcine epidemic diarrhea virus (PEDV) have been identified in swine, while the cross protection between the G2a and G1a subgenotypes is undetermined. Hence, in the present study, we attempted to observe a comparative pathogenicity and cross protection of G1a (CV777) and G2a (CH/JX/01) PEDVs. Initially pregnant sows were vaccinated twice with the two kinds of inactivated G1a- and G2a-based PEDV vaccines, respectively and the delivered neonatal piglets were challenged with prototype isolates of G1a and G2a PEDVs, and then the pathogenicity and cross-protection in neonatal piglets were observed. The results showed that CH/JX/01, a highly virulent and dominant G2a PEDV strain currently circulating in China had more severe pathogenicity in vitro and in vivo, and induced more strong immune responses, including higher titers of sIgA in maternal milk than that induced by CV777 PEDV, a prototype of G1a PEDV strain. All piglets from the sows immunized with CH/JX/01 could not only survive when challenged with the homologous PEDV, but also be fully protected when challenged with heterogenous G1a PEDV. In contrast, the piglets from the sows immunized with CV777 could be protected when challenged with homologous PEDV and only partially protected when challenged with heterologous G2a strain of PEDV (CH/JX/01). The findings of this study provide new insights into the pathogenicity, antigenicity, and immunogenicity of currently circulating wild type G2a PEDV, which might be valuable for the development of novel PEDV vaccine candidates with improved efficacy.

The apetalous trait of rapeseed (Brassica napus, AACC, 2n = 38) is important for breeding an ideal high-yield rapeseed with superior klendusity to Sclerotinia sclerotiorum. Currently, the molecular mechanism underlying the apetalous trait of rapeseed is unclear. In this study, 14 petal regulators genes were chosen as target genes (TGs), and the expression patterns of the 14 TGs in the AH population, containing 189 recombinant inbred lines derived from a cross between apetalous “APL01” and normal “Holly,” were analyzed in two environments using qRT-PCR. Phenotypic data of petalous degree (PDgr) in the AH population were obtained from the two environments. Both quantitative trait transcript (QTT)-association mapping and expression QTL (eQTL) analyses of TGs expression levels were performed to reveal regulatory relationships among TGs and PDgr. QTT mapping for PDgr determined that PLURIPETALA (PLP) was the major negative QTT associated with PDgr in both environments, suggesting that PLP negatively regulates the petal development of line “APL01.” The QTT mapping of PLP expression levels showed that CHROMATIN-REMODELING PROTEIN 11 (CHR11) was positively associated with PLP expression, indicating that CHR11 acts as a positive regulator of PLP expression. Similarly, QTT mapping for the remaining TGs identified 38 QTTs, associated with 13 TGs, and 31 QTTs, associated with 10 TGs, respectively, in the first and second environments. Additionally, eQTL analyses of TG expression levels showed that 12 and 11 unconditional eQTLs were detected in the first and second environment, respectively. Based on the QTTs and unconditional eQTLs detected, we presented a hypothetical molecular regulatory network in which 14 petal regulators potentially regulated the apetalous trait in “APL01” through the CHR11-PLP pathway. PLP acts directly as the terminal signal integrator negatively regulating petal development in the CHR11-PLP pathway. These findings will aid in the understanding the molecular mechanism underlying the apetalous trait of rapeseed.

Two-component regulatory systems (TCSs) play pivotal roles in bacteria sensing many different stimuli from environment. Here, we investigated the role of the LytSR TCS in spore formation in Bacillus thuringiensis (Bt) subsp. kurstaki HD73. lacZ gene fusions revealed that the transcription of the downstream genes, lrgAB, encoding two putative membrane-associated proteins, is regulated by LytSR. The sporulation efficiency of a lytSR mutant was significantly lower than that of wild-type HD73. A confocal microscopic analysis demonstrated that LytSR modulates the process of forespore engulfment. Moreover, the transcription of the lytSR operon is regulated by the mother-cell transcription factor SigE, whereas the transcription of the sporulation gene spoIIP was reduced in the lytSR mutant, as demonstrated with a β-galactosidase activity assay. These results suggest that LytSR modulates forespore engulfment by affecting the transcription of the spoIIP gene in Bt.

Patients with late-life depression (LLD) have a higher incident of developing dementia, especially individuals with memory deficits. However, little is known about the white matter characteristics of LLD with memory deficits (LLD-MD) in the human connectome, especially for the rich-club coefficient, which is an indicator that describes the organization pattern of hub in the network. To address this question, diffusion tensor imaging of 69 participants [15 LLD-MD patients; 24 patients with LLD with intact memory (LLD-IM); and 30 healthy controls (HC)] was applied to construct a brain network for each individual. A full-scale battery of neuropsychological tests were used for grouping, and evaluating executive function, processing speed and memory. Rich-club analysis and global network properties were utilized to describe the topological features in each group. Network-based statistics (NBS) were calculated to identify the impaired subnetwork in the LLD-MD group relative to that in the LLD-IM group. We found that compared with HC participants, patients with LLD (LLD-MD and LLD-IM) had relatively impaired rich-club organizations and rich-club connectivity. In addition, LLD-MD group exhibited lower feeder and local connective average strength than LLD-IM group. Furthermore, global network properties, such as the shortest path length, connective strength, efficiency and fault tolerant efficiency, were significantly decreased in the LLD-MD group relative to those in the LLD-IM and HC groups. According to NBS analysis, a subnetwork, including right cognitive control network (CCN) and corticostriatal circuits, were disrupted in LLD-MD patients. In conclusion, the disease effects of LLD were prevalent in rich-club organization. Feeder and local connections, especially in the subnetwork including right CCN and corticostriatal circuits, were further impaired in those with memory deficits. Global network properties were disrupted in LLD-MD patients relative to those in LLD-IM patients.

BACKGROUND:Congenital deafness is one of the most distressing disorders affecting humanity and exhibits a high incidence worldwide. Most cases of congenital deafness in the Chinese population are caused by defects in a limited number of genes. A convenient and reliable method for detecting common deafness-related gene mutations in the Chinese population is required. METHODS:We developed a PCR-reverse dot blot (RDB) assay for screening 20 hotspot mutations of GJB2, GJB3, SLC26A4, and MT-RNR1, which are common non-syndromic hearing loss (NSHL)-associated genes in the Chinese population. The PCR-RDB assay consists of multiplex PCR amplifications of 10 fragments in the target sequence of the four above-mentioned genes in wild-type and mutant genomic DNA samples followed by hybridization to a test strip containing allele-specific oligonucleotide probes. We applied our method to a set of 225 neonates with deafness gene mutations and 30 normal neonates. RESULTS:The test was validated through direct sequencing in a blinded study with 100% concordance. CONCLUSIONS:The results demonstrated that our reverse dot blot assay is a reliable and effective genetic screening method for identifying carriers and individuals with NSHL among the Chinese population.

The Gram-positive pathogen Bacillus cereus is able to grow in chains of rod-shaped cells, but the regulation of chaining remains largely unknown. Here, we observe that glucose-grown cells of B. cereus ATCC 14579 form longer chains than those grown in the absence of glucose during the late exponential and transition growth phases, and identify that the clhAB2 operon is required for this chain lengthening phenotype. The clhAB2 operon is specific to the B. cereus group (i.e., B. thuringiensis, B. anthracis and B. cereus) and encodes two membrane proteins of unknown function, which are homologous to the Staphylococcus aureus CidA and CidB proteins involved in cell death control within glucose-grown cells. A deletion mutant (ΔclhAB2) was constructed and our quantitative image analyses show that ΔclhAB2 cells formed abnormal short chains regardless of the presence of glucose. We also found that glucose-grown cells of ΔclhAB2 were significantly wider than wild-type cells (1.47 μm ±CI95% 0.04 vs 1.19 μm ±CI95% 0.03, respectively), suggesting an alteration of the bacterial cell wall. Remarkably, ΔclhAB2 cells showed accelerated autolysis under autolysis-inducing conditions, compared to wild-type cells. Overall, our data suggest that the B. cereus clhAB2 operon modulates peptidoglycan hydrolase activity, which is required for proper cell shape and chain length during cell growth, and down-regulates autolysin activity. Lastly, we studied the transcription of clhAB2 using a lacZ transcriptional reporter in wild-type, ccpA and codY deletion-mutant strains. We found that the global transcriptional regulatory protein CodY is required for the basal level of clhAB2 expression under all conditions tested, including the transition growth phase while CcpA, the major global carbon regulator, is needed for the high-level expression of clhAB2 in glucose-grown cells.

Acetohydroxyacid synthase (AHAS), also called acetolactate synthase, is a key enzyme involved in the first step of the biosynthesis of the branched-chain amino acids valine, isoleucine and leucine. Acetohydroxyacid synthase-inhibiting herbicides (AHAS herbicides) are five chemical families of herbicides that inhibit AHAS enzymes, including imidazolinones (IMI), sulfonylureas (SU), pyrimidinylthiobenzoates, triazolinones and triazolopyrimidines. Five AHAS genes have been identified in rapeseed, but little information is available regarding the role of miRNAs in response to AHAS herbicides. In this study, an AHAS herbicides tolerant genotype and a sensitive genotype were used for miRNA comparative analysis. A total of 20 small RNA libraries were obtained of these two genotypes at three time points (0h, 24 h and 48 h) after spraying SU and IMI herbicides with two replicates. We identified 940 conserved miRNAs and 1515 novel candidate miRNAs in Brassica napus using high-throughput sequencing methods combined with computing analysis. A total of 3284 genes were predicted to be targets of these miRNAs, and their functions were shown using GO, KOG and KEGG annotations. The differentiation expression results of miRNAs showed almost twice as many differentiated miRNAs were found in tolerant genotype M342 (309 miRNAs) after SU herbicide application than in sensitive genotype N131 (164 miRNAs). In additiond 177 and 296 miRNAs defined as differentiated in sensitive genotype and tolerant genotype in response to SU herbicides. The miR398 family was observed to be associated with AHAS herbicide tolerance because their expression increased in the tolerant genotype but decreased in the sensitive genotype. Moreover, 50 novel miRNAs from 39 precursors were predicted. There were 8 conserved miRNAs, 4 novel miRNAs and 3 target genes were validated by quantitative real-time PCR experiment. This study not only provides novel insights into the miRNA content of AHAS herbicides tolerant rapeseed in response to AHAS herbicides, but also demonstrates that miRNAs may be involved in AHAS herbicides tolerance.