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The recent discovery of superconductivity in infinite-layer nickelates generates tremendous research endeavors, but the ground state of their parent compounds is still under debate. Here, we report experimental evidences for the dominant role of Kondo scattering in the underdoped Nd1-xSrxNiO2 thin films. A resistivity minimum associated with logarithmic temperature dependence in both longitudinal and Hall resistivities are observed in the underdoped Nd1-xSrxNiO2 samples before the superconducting transition. At lower temperatures down to 0.04 K, the resistivities become saturated, following the prediction of the Kondo model. A linear scaling behavior $\sigma _{{\boldsymbol{xy}}}^{{{\boldsymbol AHE}}}{\rm{\ }}\sim{\rm{\ }}{\sigma }_{{\boldsymbol{xx}}}$ between anomalous Hall conductivity $\sigma _{{\boldsymbol{xy}}}^{{\boldsymbol{AHE}}}$ and conductivity ${\sigma }_{{\boldsymbol{xx}}}{\rm{\ }}$is revealed, verifying the dominant Kondo scattering at low temperature. The effect of weak (anti-)localization is found to be secondary. Our experiments can help clarifying the basic physics in the underdoped Nd1-xSrxNiO2 infinite-layer thin films.

Adenosine is an immunosuppressive factor that limits anti-tumor immunity through the suppression of multiple immune subsets including T cells via activation of the adenosine A2A receptor (A2AR). Using both murine and human chimeric antigen receptor (CAR) T cells, here we show that targeting A2AR with a clinically relevant CRISPR/Cas9 strategy significantly enhances their in vivo efficacy, leading to improved survival of mice. Effects evoked by CRISPR/Cas9 mediated gene deletion of A2AR are superior to shRNA mediated knockdown or pharmacological blockade of A2AR. Mechanistically, human A2AR-edited CAR T cells are significantly resistant to adenosine-mediated transcriptional changes, resulting in enhanced production of cytokines including IFNγ and TNF, and increased expression of JAK-STAT signaling pathway associated genes. A2AR deficient CAR T cells are well tolerated and do not induce overt pathologies in mice, supporting the use of CRISPR/Cas9 to target A2AR for the improvement of CAR T cell function in the clinic., Activation of the adenosine receptor A2AR is associated with suppression of T cell function in the tumor microenvironment. To overcome immunosuppression, here the authors show that CRISPR/Cas9 mediated deletion of A2AR enhances CAR T cell effector functions without altering memory or persistence properties, improving CAR-T mediated tumor control in pre-clinical models.

Orthopedic infection is a serious complication in surgeries and remains a great challenge in clinics. Here, the natural antimicrobial compound vanillic acid-loaded gold nanospheres/mesoporous silica nanoparticles (VA@Au-MSNs) were fabricated for chemo-photothermal synergistic therapy to orthopedic infections. The shape and morphology of Au-MSN and VA@Au-MSN were observed by scanning electron microscopy and transmission electron microscopy. The properties of VA@Au-MSN or related components were characterized by dynamic light scattering, thermogravimetric analysis, Brunauer–Emmett–Teller (BET) analysis, and photothermal analysis. Vanillic acid released from VA@Au-MSN was detected in phosphate-buffered saline. A cytotoxicity test and an antibacterial assessment were performed to explore the biosafety and antibacterial activity of VA@Au-MSN, respectively. The results showed that Au-MSN possessed a high BET surface area (458 m2/g). After loading vanillic acid, the BET surface area reduced to 72 m2/g. The loading efficiency of Au-MSN was 18.56%. Under 808 nm laser irradiation, the temperature at the wound site injected with the Au-MSN solution in the mouse increased from 24 to 60 °C within about 12 s. Also, the high temperature could promote the release of vanillic acid from VA@Au-MSN. Additionally, VA@Au-MSN has no obvious cytotoxicity to MC3T3-E1 cells, but the generated local hyperthermia and the VA released from VA@Au-MSN had excellent antibacterial activity against Staphylococcus aureus in a synergistic way. In conclusion, the VA@Au-MSN with biosafety and excellent antibacterial performance might be applied for the treatment of orthopedic infection.

Chimeric antigen receptor (CAR) T cell therapy has been highly successful in hematological malignancies leading to their US Food and Drug Administration (FDA) approval. However, the efficacy of CAR T cells in solid tumors is limited by tumor-induced immunosuppression, leading to the development of combination approaches, such as adjuvant programmed cell death 1 (PD-1) blockade. Current FDA-approved methods for generating CAR T cells utilize either anti-CD3 and interleukin (IL)-2 or anti-CD3/CD28 beads, which can generate a T cell product with an effector/exhausted phenotype. Whereas different cytokine preconditioning milieu, such as IL-7/IL-15, have been shown to promote T cell engraftment, the impact of this approach on CAR T cell responses to adjuvant immune-checkpoint blockade has not been assessed. In the current study, we reveal that the preconditioning of CAR T cells with IL-7/IL-15 increased CAR T cell responses to anti-PD-1 adjuvant therapy. This was associated with the emergence of an intratumoral CD8(+)CD62L(+)TCF7(+)IRF4(–) population that was highly responsive to anti-PD-1 therapy and mediated the vast majority of transcriptional and epigenetic changes in vivo following PD-1 blockade. Our data indicate that preservation of CAR T cells in a TCF7(+) phenotype is crucial for their responsiveness to adjuvant immunotherapy approaches and should be a key consideration when designing clinical protocols.

Anthracnose is a serious fungal disease that primarily infects strawberry roots and stolons during development. Here, 91 isolates from different areas of Zhejiang province, China, were collected. Morphological characteristics were analyzed, and a phylogenetic analysis based on multiple genes (actin, internal transcribed spacer, calmodulin, glyceraldehyde-3-phosphate dehydrogenase, and chitin synthase) was performed. We found that all of the Colletotrichum species causing strawberry anthracnose belonged to the Colletotrichum gloeosporioides complex. Among them, we identified 48 isolates of C. fructicola, 21 isolates of C. siamense, 13 isolates of C. gloeosporioides, and 9 isolates of C. aenigma. C. siamense was distributed in the central and eastern regions of Zhejiang province (Hangzhou, Jinhua, Shaoxing, Ningbo, and Taizhou). This is the first report of C. siamense causing strawberry anthracnose in Zhejiang province. C. fructicola was the most dominant species causing strawberry anthracnose in Zhejiang province. We identified the four species causing strawberry anthracnose in Zhejiang province, which will improve our understanding of the strawberry anthracnose epidemic and will benefit the development of future control measures.

hine Muscat, with its excellent quality and unique Muscat aroma, is emerging as one of the most profitable table grape cultivars in Asia. However, in-depth analysis of the cultivar’s aroma profile before berries are harvest-ready is lacking. The aroma components and their concentrations undergo substantial changes during berry ripening, which provides an opportunity for producing some juice/wine products with special flavour. In this study, the evolution of free and bound aroma compounds in Shine Muscat grapes was analysed from EL-35 to EL-38. The main aroma attributes of harvest-ready berries were: ‘green’, ‘sweet’, ‘floral’ and ‘fruity’. The headspace SPME-GC-MS analysis revealed that alcohols were the most abundant free and bound compounds in Shine Muscat. Furthermore, the free forms of hexanal, β-damascenone, and (E, Z)-2,6-nonadienal determined the aroma characteristics of the grapes directly, while the bound forms of β-damascenone, (E, Z)-2,6-nonadienal, and 2-hexanol determined the aroma of Shine Muscat that cannot to be smelled directly. Taking all indicators together, we believe that picking Shine Muscat grapes at EL-37 (when a minimum TSS of 17% has been reached) maintains its fine aroma characteristics. These results lay the foundation for the further development, utilisation and study of the aroma characteristics of Shine Muscat grapes.

Anoectochilus roxburghii is an important Chinese herbal medicine plant belonging to Orchidaceae and known as Jinxianlian. This orchid is cultivated and mostly adopted to treat diabetes and hepatitis. About 2 billion artificially cultivated seedlings of Jinxianlian are required each year and approximately $600 million in fresh A. roxburghii seedlings is produced in China. From 2011, sporadic occurrence of stem rot on Jinxianlian have been observed in greenhouses in Jinhua City (N29°05', E119°38'), Zhejiang Province. In 2018, nearly 30% of seedlings of Jinxianlian grown in greenhouse conditions were affected by stem rot in Jinhua City. Symptoms initially occurred in the stem at the soil line causing dark discoloration lesions, rotted tissues, wilting, and eventually leading to the death of the plants. A total of 23 diseased seedlings collected from seven different greenhouses were surface sterilized with 1.5% sodium hypochlorite for 3 min, then rinsed in water. Pieces of tissues disinfected from each sample were plated on 2% potato dextrose agar (PDA), and incubated at 25°C in the dark for 5 days (Kirk et al. 2008). A total of 19 isolates were recovered. They developed colonies with purple mycelia and beige or orange colors after 7 days of incubation under 25°C on PDA and carnation leaf agar (CLA) media (Kirk et al. 2008; Zhang et al. 2016). Colonies on PDA had an average radial growth rate of 3.1 to 4.0 mm /d at 25°C. Colony surface was pale vinaceous, floccose with abundant aerial mycelium. On CLA, aerial mycelium was sparse with abundant bright orange sporodochia forming on the carnation leaves. Microconidia were hyaline and oval-ellipsoid to cylindrical (3.7 to 9.3 × 1.3 to 2.9 μm) (n=19). Macroconidia were 3 to 5 septate and fusoid-subulate with a pedicellate base (27.4 to 35.6 × 3.2 to 4.2 μm) (n=19). These morphological features were consistent with Fusarium oxysporum (Sun et al. 2008; Lombard et al., 2019). To confirm the identification based on these morphological features, the internal transcribed spacer region (ITS) and translation elongation factor1 (TEF) were amplified from the DNA of 3 out of 19 isolates chosen at random respectively using the set primer ITS1/ITS4 and EF1/ EF2 (Sun, S., et al. 2018; Lombard et al., 2019). BLAST analysis revealed that the ITS sequences (OK147619, OK147620, OK147621) had 99% identity to that of F. oxysporum isolate JJF2 (GenBank MN626452) and TEF sequence (OK155999, OK156000, OK156001) had 100% identity to that of F. oxysporum isolate gss100 (GenBank MH341210). A multilocus phylogenetic analysis by Bayesian inference (BI) and maximum likelihood (ML) trees based on ITS and TEF indicated that the pathogen grouped consistently with F. oxysporum. Three out of 19 isolates chosen at random were selected to evaluate pathogenicity. Uninfected healthy A. roxburghii seedlings about 40 day-old planted in sterilized substrates were sprayed with distilled water containing 2 x 106 conidia per ml suspensions as inoculums, and plants sprayed with distilled water alone served as controls. Plants were then incubated at 25°C and 85% relative humidity. Ten plants were inoculated for each isolate. After 10 days, all plants inoculated developed stem rot symptoms, while control plants remained healthy. Cultures of Fusarium spp. were re-isolated only from inoculated plants with the frequency of 100% and re-identified by morphological characteristics as F. oxysporum, fulfilling Koch's postulates. To the best of our knowledge, this is the first report of F. oxysporum causing stem rot on A. roxburghii seedlings. As F. oxysporum is a devastating pathogenic fungus with a broad host range, measures should be taken in advance to manage stem rot of A. roxburghii.

Purpose: Response rates to immune checkpoint blockade (ICB; anti-PD-1/anti-CTLA-4) correlate with the extent of tumor immune infiltrate, but the mechanisms underlying the recruitment of T cells following therapy are poorly characterized. A greater understanding of these processes may see the development of therapeutic interventions that enhance T-cell recruitment and, consequently, improved patient outcomes. We therefore investigated the chemokines essential for immune cell recruitment and subsequent therapeutic efficacy of these immunotherapies. Experimental Design: The chemokines upregulated by dual PD-1/CTLA-4 blockade were assessed using NanoString-based analysis with results confirmed at the protein level by flow cytometry and cytometric bead array. Blocking/neutralizing antibodies confirmed the requirement for key chemokines/cytokines and immune effector cells. Results were confirmed in patients treated with immune checkpoint inhibitors using single-cell RNA-sequencing (RNA-seq) and paired survival analyses. Results: The CXCR3 ligands, CXCL9 and CXCL10, were significantly upregulated following dual PD-1/CTLA-4 blockade and both CD8+ T-cell infiltration and therapeutic efficacy were CXCR3 dependent. In both murine models and patients undergoing immunotherapy, macrophages were the predominant source of CXCL9 and their depletion abrogated CD8+ T-cell infiltration and the therapeutic efficacy of dual ICB. Single-cell RNA-seq analysis of patient tumor-infiltrating lymphocytes (TIL) revealed that CXCL9/10/11 was predominantly expressed by macrophages following ICB and we identified a distinct macrophage signature that was associated with positive responses to ICB. Conclusions: These data underline the fundamental importance of macrophage-derived CXCR3 ligands for the therapeutic efficacy of ICB and highlight the potential of manipulating this axis to enhance patient responses.

This study aims to investigate the feasibility of using hyperspectral remote sensing technique by visible-near infrared spectroradiometer (VNIR, FieldSpec HandHeld 2) for rapid water monitoring of heavy metal, followed by comparison of different spectral preprocessing methods for the development of quantitative predictive model. The water samples evaluated in this study were prepared in our laboratory by dilution of stock solutions. Heavy metals of lead (Pb), zinc (Zn) and copper (Cu) in the range of concentration between 100 to 2000 mg/L were selected as the target samples in this study. The sensitive bands for the target metals were characterized in the range from 800 nm to 1075 nm, based on the reflectance spectral data. Spectral data for developing of the quantitative predictive model was first preprocessed with first derivative and logarithm transformation, followed by establishing of the prediction model using multivariate linear regression (MLR). It was observed that increase in the number of sensitive bands for the MLR can significantly improve the adjusted R2 for the model. The prediction model for Cu was found to have the highest adjusted R2 of 0.92 and least normalized root mean square error (NRMSE) of 0.065, while using the reflectance values of 7 sensitive bands. This result could be attributed to the blue color characteristic of the solution, whereas the others remain clear. Additionally, the first derivative transformation was determined as the best method for predicting Pb, whereas the logarithm transformation provided the best outcomes for predicting Cu and Zn.

The function of MR1-restricted mucosal-associated invariant T (MAIT) cells in tumor immunity is unclear. Here we show that MAIT cell-deficient mice have enhanced NK cell-dependent control of metastatic B16F10 tumor growth relative to control mice. Analyses of this interplay in human tumor samples reveal that high expression of a MAIT cell gene signature negatively impacts the prognostic significance of NK cells. Paradoxically, pre-pulsing tumors with MAIT cell antigens, or activating MAIT cells in vivo, enhances anti-tumor immunity in B16F10 and E0771 mouse tumor models, including in the context of established metastasis. These effects are associated with enhanced NK cell responses and increased expression of both IFN-γ-dependent and inflammatory genes in NK cells. Importantly, activated human MAIT cells also promote the function of NK cells isolated from patient tumor samples. Our results thus describe an activation-dependent, MAIT cell-mediated regulation of NK cells, and suggest a potential therapeutic avenue for cancer treatment., Mucosal-associated invariant T (MAIT) cells facilitate anti-microbial responses, but their functions in cancer protection is unclear. Here the authors show that activated MAIT cells induce an IFN-γ transcriptome in natural killer (NK) cells and enhance NK-dependent anti-cancer immunity in mice, thereby hinting a new avenue for cancer therapy.

Currently, the role of Pannexin-1, a homomeric membrane hemichannel on the neuron cell membrane, in the development of spinal cord injury (SCI) is largely unknown. Herein, we assessed the contribution of Panx1 in the development of SCI. The SCI in vitro model was established using rat primary spinal neurocytes treated with hydrogen peroxide (H2O2). Effects of Panx1 overexpression or depletion in spinal neurocytes were analyzed by lentivirus-mediated transfection of Panx1 and interference sh-Panx1. Decreased cell viability was seen in SCI cells, which was further enhanced under Panx1 overexpression and mitigated by Panx1 deficiency. H2O2 induced an increase of intracellular Ca2+ signal and upregulated level of the proapoptotic protein Bax, and apoptosis pathway proteins including cleaved Caspase-3 and PARP1, which was enhanced by Panx1 overexpression or attenuated by Panx1 depletion. On the other hand, H2O2 treatment suppressed the level of antiapoptotic protein Bcl-2, which was further decreased by Panx1 overexpression or mitigated by Panx1 depletion. The results indicate that Panx1 was involved in the intracellular Ca2+ overload of SCI cells by accelerating extracellular Ca2+ influx, which promoted the apoptosis of spinal neurocytes through Ca2+ dependent pathways, thus aggravating the secondary injury of SCI.

Undissolved gas bubbles, which are widely formed in marine sediments, could modify the behavior of the soil. To date, the cyclic behavior of fine-grained gassy soil has been rarely studied,...

Long non-coding RNAs (lncRNAs) play vital roles in the pathogenesis and development of multiple cancers, including osteosarcoma (OS). The present study aims to investigate the role of LINC00665 in OS progression.The expression levels of LINC00665 and miR-3619 were assessed by RT-qPCR. The correlation between LINC00665 and miR-3619 expression was evaluated by Pearson's correlation analysis. The interaction between LINC00665 and miR-3619 was predicted by starBase, which was further confirmed by Luciferase reporter assay and RIP assay. The viability, invasion, and migration of OS cells were analyzed by CCK-8 and transwell assays.LINC00665 expression was upregulated in OS tissues and cell lines, and the high level of LINC00665 was associated with poor prognosis in OS. Moreover, LINC00665 knockdown attenuated the viability, invasion, and migration of OS cells. In addition, miR-3619 was demonstrated to be a target of LINC00665. Overexpression of miR-3619 inhibited OS progression, while this effect was abolished by the upregulation of LINC00665.We demonstrated that LINC 00665 accelerated OS development by targeting miR-3619. These findings might provide potential treatment strategies for patients with OS.

The purpose of this study was to investigate the role of microRNA-488-3p in the proliferation, invasion and migration of lung cancer cells and to further explore the potential regulatory mechanisms.MicroRNA-488-3p expression in 46 pairs of tumor tissue and paracancerous tissue specimens collected from non-small cell lung cancer (NSCLC) patients were measured through quantitative real-time polymerase chain reaction (qRT-PCR) method, and the interplay between microRNA-488-3p expression and some clinical indicators of these subjects was also analyzed. In addition, microRNA-488-3p overexpression models were constructed in NSCLC cell lines, and then Cell Counting Kit-8 (CCK-8) test and transwell assays were carried out to evaluate the effect of microRNA-488-3p on the NSCLC cell functions. Furthermore, bioinformatics analysis and luciferase reporter gene assay were carried out to uncover the potential interaction between microRNA-488-3p and its downstream gene ADAM9.QPCR results revealed that microRNA-488-3p showed a significant lower expression in NSCLC tissue samples than in adjacent normal ones. In comparison to patients with high expression of microRNA-488-3, patients with low expression of microRNA-488-3 exhibited higher incidence of lymph node or distant metastasis and lower survival rate. In vitro cell experiments showed that, in comparison to control group, overexpression of microRNA-488-3p significantly weakened the proliferation ability as well as the invasion and migration of NSCLC cells. Subsequently, a significant increase in ADAM9 expression in NSCLC tissue samples was found, which indicated its negative correlation with microRNA-488-3p. In addition, cell recovery experiment demonstrated that overexpression of ADAM9 could counteract the impact of microRNA-488-3p upregulation on the proliferation and invasion ability of NSCLC cells, and the two may thus together affect the malignant progression of NSCLC.It can be concluded that microRNA-488-3p, which is associated with the incidence of metastasis in NSCLC patients, can inhibit the malignant progression of NSCLC cells by modulating ADAM9 expression.

The use of optical properties as key parameters has been widely used in water quality monitoring, which accelerates the advances of remote sensing in the field of environmental monitoring. Current analytical methods for determining heavy metals in water include flame atomic absorption spectrometry (FAAS), atomic adsorption spectrophotometry (AAS) and inductively coupled plasma (ICP) spectroscopy, which typically require use of chemicals for sample processing and pretreatment as well as high capital input for analysis. Therefore, this study aims at investigating the potential of using non-destructive approaches for rapid water monitoring of heavy metal from green chemistry perspective. The proposed non-destructive sensing techniques include X-ray fluorescence spectrometer (XRF) and visible-near infrared spectroradiometer (VNIR). The former is an elemental analyser specifically for elements with relatively high atomic number, and the latter measures the reflectance or transmittance from samples. Heavy metals of lead (Pb), zinc (Zn) and copper (Cu) were selected as the target water constitutes in the study. The results from the analysis were then be used for determining a correlation model through chemometric approaches. Our results demonstrated that both of the target metals could be analysed via the proposed analytical methods. Reasonable agreements between the measurements from XRF and ICP were observed, whereas moderate correlations were perceived for simple linear regression model using spectral information from VNIR. Results from this study are expected to provide useful information on rapid identification of metal-polluting sources.

OBJECTIVE: To explore the correlation between different personality characteristics and self-management attitude such as medication, exercise and diet in patients with type 2 diabetes mellitus. METHODS: The patients with type 2 diabetes mellitus from 4 Community Healthcare Services and 22 affiliated community stations of Tongzhou District and Shunyi District of Beijing were selected as subjects. The Chinese big five personality inventory and the self-designed scale including the attitudes of medication, exercise and diet were used in the study. RESULTS: In this study, 642 subjects were finally included, among whom the sex ratio of male and female was basically the same, 61.21% were over 61 years old. In this study, different genders had differences in neurotic personality (P

Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer, with an unfavorable prognosis of 5-year survival rates. It is of great clinical significance to further search for more efficacious and novel targets for diagnosis and therapeutic strategies. This study aimed at clarifying the role of long non-coding RNA (lncRNA) NORAD in proliferation, invasion and migration and tumor growth of NSCLC.In this study, mRNA levels of lncRNA NORAD were examined by RT-PCR. CCK-8 assay was applied to test cell viability. Furthermore, wound healing assay and transwell assay were performed to detect the migration and invasion of A549 cells, respectively. Immunohistochemistry was applied to assess the levels of CXC chemokine receptor (CXCR) 4 and CXC chemokine ligand (CXCL) 12. Mice models of NSCLC in vivo were exploited to further examine the potential role of NORAD in tumor growth. Key proteins related to Ras homolog gene family member A (RhoA) GTPase/Rho-associated kinase (RhoA/ROCK) pathway were determined by Western blot.NORAD has elevated the levels in NSCLC tissues and cells. NORAD interference dramatically inhibited tumor growth and suppressed A549 cell proliferation, migration and invasion by downregulating CXCR4 and CXCL12 expression. RhoA/ROCK signaling pathway was activated in NSCLC.This study revealed that the downregulation of lncRNA NORAD could slow down the progression of NSCLC by regulating CXCR4 and RhoA/ROCK signaling pathway.

The origins and phylogeny of different sheep breeds has been widely studied using polymorphisms within the mitochondrial hypervariable region. However, little is known about the mitochondrial DNA (mtDNA) content and phylogeny based on mtDNA protein-coding genes. In this study, we assessed the phylogeny and copy number of the mtDNA in eight indigenous (population size, n=184) and three introduced (n=66) sheep breeds in China based on five mitochondrial coding genes (COX1, COX2, ATP8, ATP6 and COX3). The mean haplotype and nucleotide diversities were 0.944 and 0.00322, respectively. We identified a correlation between the lineages distribution and the genetic distance, whereby Valley-type Tibetan sheep had a closer genetic relationship with introduced breeds (Dorper, Poll Dorset and Suffolk) than with other indigenous breeds. Similarly, the Median-joining profile of haplotypes revealed the distribution of clusters according to genetic differences. Moreover, copy number analysis based on the five mitochondrial coding genes was affected by the genetic distance combining with genetic phylogeny; we also identified obvious non-synonymous mutations in ATP6 between the different levels of copy number expressions. These results imply that differences in mitogenomic compositions resulting from geographical separation lead to differences in mitochondrial function.

The UL13 protein of the duck enteritis virus (DEV), predicted to encode a Ser/Thr protein kinase, belongs to the family of conserved herpesvirus protein kinases (CHPK), which plays an important role in herpesvirus proliferation. In this study, truncated UL13 was expressed as a fusion protein of approximately 44 kDa using a prokaryotic expression system, and this protein was used to generate a specific anti-UL13 antibody. This antibody detected UL13 starting at 4 h post infection in duck embryonic fibroblast cells and identified UL13 to be present in both the cytoplasm and the nucleus. UL13 RNA was found to be transcribed starting at 2 h post infection, and the synthesis of the UL13 mRNA was found to be sensitive to the protein synthesis inhibitor cycloheximide (CHX) and tolerant of the DNA polymerase inhibitor ganciclovir (GCV). Its nuclear location and status as an early gene suggested that DEV UL13 might play important roles in DEV replication, which was confirmed by comparing the proliferation of a UL13-knockout mutant virus, a revertant virus, and the parent virus in cell culture. The specific mechanisms of UL13 in viral replication need to be further studied.

Anthracnose is a serious fungal disease that primarily infects strawberry roots and stolons during development. Here, 91 isolates from different areas of Zhejiang province, China, were collected. Morphological characteristics were analyzed, and a phylogenetic analysis based on multiple genes (actin, internal transcribed spacer, calmodulin, glyceraldehyde-3-phosphate dehydrogenase, and chitin synthase) was performed. We found that all of the

CRISPR/Cas9 technologies have revolutionized our understanding of gene function in complex biological settings, including T cell immunology. Current CRISPR-mediated gene editing strategies in T cells require in vitro stimulation or culture that can both preclude the study of unmanipulated naive T cells and alter subsequent differentiation. In this study, we demonstrate highly efficient gene editing within uncultured primary naive murine CD8+ T cells by electroporation of recombinant Cas9/sgRNA ribonucleoprotein immediately prior to in vivo adoptive transfer. Using this approach, we generated single and double gene knockout cells within multiple mouse infection models. Strikingly, gene deletion occurred even when the transferred cells were left in a naive state, suggesting that gene deletion occurs independent of T cell activation. Finally, we demonstrate that targeted mutations can be introduced into naive CD8+ T cells using CRISPR-based homology-directed repair. This protocol thus expands CRISPR-based gene editing approaches beyond models of robust T cell activation to encompass both naive T cell homeostasis and models of weak activation, such as tolerance and tumor models.

Background Although his bundle pacing (HBP) can achieve physiological electrical activation of the ventricles, its clinical use is limited by lower success rates, high and unstable pacing thresholds and loss of capture. Left bundle branch pacing (LBBP) has been proved to be able to correct Left bundle branch block (LBBB) and generate a narrower QRS duration than conventional RV pacing. However, its effects on ventricular synchronism and contraction function remains unknown. The current study is aimed to compare the echocardiographic characteristics between HBP and LBBP, and to explore whether LBBP leads to a comparable cardiac synchrony and deformation in comparison with HBP. Methods Forty-six pacing-indicated patients were prospectively enrolled. Twenty-nine patients underwent LBBP (17 male patients, mean age 69.6±13.7yrs, the LBBP group) and 17 patients underwent HBP (13 male patients, mean age 70.4±14.7yrs, the HBP group). LBBP was achieved by trans-septal method in the basal ventricular septum. Left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV), left ventricular ejection fraction (LVEF), and tricuspid annulus plane systolic excursion (TAPSE) were obtained. Strains and time to peak strains of right ventricular free wall and 16 left ventricle segments were analyzed using two-dimensional speckle tracking echocardiography (2D STE). The standard deviation of time to peak strains of 16 left ventricular segments was calculated as PSD. Results Compared to the baseline, time to peak longitudinal strain (TTPS) of apical septum, apical lateral wall were shortened after 6 months of HBP, while they didn't change significantly after 6 months of LBBP. After pacemaker implantation, the LBBP group had a delayed TTPS of apical septum, apical lateral wall and basal RV free wall than the HBP group (LBBP vs. HBP: apical septum,358.44±61.98ms vs. 296.43±29.47ms; apical lateral wall, 373.11±55.80ms vs. 299.00±83.45ms; basal RV free wall, 404.31±72.93ms vs. 334.50±39.95ms, all p0.05). Compared to the baseline, global left ventricular longitudinal strain (LVGLS) and longitudinal strain of RV free wall (RVLS) were deteriorated after 6 months of HBP, while they were preserved in the LBBP group. After 6-month pacing, LVGLS and RVLS were significantly stronger in the LBBP group than those in the HBP group. (LVGLS, −16.10±3.75% vs. −13.18±4.11%; RVLS, −17.50±5.46% vs. −13.70±4.35%, both p Conclusion Patients received LBBP had a comparable left ventricular synchronism and a better myocardial contraction compared to patients with HBP. LBBP may be a promising alternative pacing strategy. Two-dimensional STE is more sensitive than conventional echocardiography in assessing cardiac synchrony and segmental deformation.

目的 探讨我国GATA2突变相关儿童原发性骨髓增生异常综合征（MDS）的发生情况、临床特点及分子生物学特征。 方法 回顾性分析2007年1月至2018年1月129例儿童原发性MDS患者临床资料，采用二代测序技术检测GATA2及髓系恶性肿瘤相关基因突变情况。分析基因突变谱及其与临床表现型的关系。 结果 在所有129例患者中，11例（8.5%）检出GATA2胚系突变。在50例MDS伴原始细胞增高（MDS-EB）和急性髓系白血病伴MDS相关改变（AML-MRC）患者中，GATA2胚系突变占14.0%。GATA2突变多位于第二个锌指（ZF2）区。多因素分析结果显示，SETBP1体细胞突变（P=0.041，OR=9.003，95%CI 1.098~73.787）和独立的7号染色体单体（P=0.002，OR=24.835，95%CI 3.305~186.620）与GATA2胚系突变显著相关。与GATA2野生型的患者相比，GATA2突变型患者中位发病年龄更大[8（1~16）岁对6岁（1月龄~18岁），P=0.035]，更易伴有7号染色体单体（72.7%对5.2%，P

Lung cancer, which is typically diagnosed at later stages, is a leading cause of cancer death among both males and females given its highly invasive and rapidly metastasizing nature. Rho GTPase activating protein 15 (ARHGAP15) is a member of the RhoGAP family and functions in multiple biological processes, such as cell proliferation and migration. However, the effect of ARHGAP15 in lung cancer and its underlying molecular mechanisms remain unclear.In this study, immunohistochemistry and Real Time PCR were performed to detect ARHGAP15 expression in lung cancer tissues and cells. Proliferation, transwell, and Western blot assays were further performed to explore the role and underlying mechanism of ARHGAP15 in lung cancer.Reduced ARHGAP15 expression was observed in lung cancer tissues and cells. In vitro upregulation of ARHGAP15 in lung cancer cells strongly suppressed cell proliferation, migration, and invasion and was accompanied by reduced matrix metalloproteinase-2 (MMP2), MMP9, vascular endothelial growth factor (VEGF) expression, and the phosphorylation of the signal transducer and activator of transcription-3 (p-STAT3). In contrast, interleukin-6 (IL-6) had the opposite effect and the induction of IL-6 was counteracted by ARHGAP15 upregulation. In addition, the proliferation, migration, and cell invasion induced by ARHGAP15 silencing were potentially inhibited by the STAT3 inhibitor AG490 (100 µM), MMP2, MMP9, VEGF, and p-STAT3 levels decreased.These results suggest that ARGFAP15 suppressed the proliferation and metastasis of lung cancer cells, which may occur through the inhibition of MMP2, MMP9, and VEGF expression via the STAT3 pathway inactivation.

Previous studies have indicated that β2-adrenergic receptor (ADRB2) genetic polymorphism is related to the risk of asthma, but the results still have some controversy and uncertainty. To this end, the meta-analysis was performed, including all studies that can be used to assess the correlation between ADRB2 polymorphism and asthma susceptibility.The related papers on ADRB2 polymorphisms and asthma were systematically reviewed in databases of PubMed, EMBASE, Cochrane Library, and WanFang, Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were measured. The sensitivity analysis and publication bias were evaluated to investigate the correlation.This meta-analysis included 57 papers in total involving 11,157 cases and 12,281 controls. Results illustrated that the C79G variant genotypes owned a reduced effect on asthma susceptibility (G vs. C: OR=0.94, p=0.037). In the age stratification analysis, C79G polymorphism owned a reduced effect on asthma risk for children (GG vs. CC: OR=0.69, p=0.002; GG vs. CC+CG: OR=0.65, p0.001). Furthermore, in the ethnic stratification analysis, the C79G variant genotypes also owned a reduced effect on asthma in Asians (GG vs. CC: OR=0.80, p=0.027; GG vs. CC+CG: OR=0.81, p=0.02). Besides, for A46G polymorphism, the ethnic stratification analysis demonstrated that the A46G variant owned an increased effect on asthma susceptibility among Caucasians (G vs. A: OR=1.15, p=0.043). For C491T polymorphism, a considerable reduced effect was found between C491T and asthma susceptibility for children (CT vs. CC: OR=0.70, p=0.03). In the ethnic stratification analysis, the effect was also considerable in the Caucasian subjects.The present meta-analysis demonstrated that C79G and C491T polymorphism may be a defensive factor for asthma, while A46G polymorphism may be a risk factor for asthma among the Caucasian population.

Two stages, induction stage and pore-formed stage, were distinguished in Al2Au’s dealloying process in HCl solutions by OCP, SEM and XPS characterization. In induction stage, the Au state with binding energy 85.4 eV (labelled as Al2Au (I)) was transformed into the state 84.7 eV (Al2Au (II)); in pore-formed stage, nanoporous structure started to be formed, Al2Au (II) and residual Al2Au (I) were transformed into the state 83.7 eV (pure Au). Multi-resolution analysis on OCP noise revealed that the induction stage and pore-formed stage undergo different corrosion modes: the former is local corrosion and the latter is global corrosion.