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Hypertension (HT) is a major cause of intracerebral hemorrhage (ICH), and hypertensive cerebral hemorrhage (HCH) has a serious impact on life quality of patients and gives society a heavy burden. This study investigated the key genes involved in HT and HCH. Three patients with HT, three with HCH, and three healthy individuals were recruited in the present study. Shared and specific differentially expressed genes (DEGs) in HT and HCH were identified using RNA sequencing and bioinformatics analysis. Functional annotation and protein–protein interaction (PPI) network construction of HT- and HCH-specific DEGs were conducted. Estimation of cell infiltration, drug prediction, and real-time qPCR (RT-qPCR) validation were performed. Compared with the controls, 502 and 1649 DEGs were identified in the HT and HCH groups, respectively. Among them, 378 DEGs were HT-specific and 633 DEGs were HCH-specific, and a total of 1771 DEGs were identified between HT and HCH. In addition, there were fewer immune cell types that differed significantly among the three groups. The RT-qPCR validation results in human subjects and cell models were generally consistent with the sequencing results. Our study may make a contribution for the understanding of the specific mechanisms of HT and HCH. Highlights Hypertension (HT) is a major cause of intracerebral hemorrhage (ICH), and hypertensive cerebral hemorrhage (HCH) has a serious impact on life quality of patients. A total of 502 and 1649 DEGs were obtained in HT and HCH, and 1771 DEGs were obtained between HT and HCH. Doxycycline, fasudil and propylthiouracil were predicted as potential drugs for HT and HCH. Our study may make a contribution for the understanding of the specific mechanisms of HT and HCH and representing a potential novel strategy for HT and HCH treatment.

IntroductionTrichoderma species establish symbiotic relationships with plants through both parasitic and mutualistic mechanisms. While some Trichoderma species act as plant pathogenic fungi, others utilize various strategies to protect and enhance plant growth.MethodsPhylogenetic positions of new species of Trichoderma were determined through multi-gene analysis relying on the internal transcribed spacer (ITS) regions of the ribosomal DNA, the translation elongation factor 1-α (tef1-α) gene, and the RNA polymerase II (rpb2) gene. Additionally, pathogenicity experiments were conducted, and the aggressiveness of each isolate was evaluated based on the area of the cross-section of the infected site.ResultsIn this study, 13 Trichoderma species, including 9 known species and 4 new species, namely, T. delicatum, T. robustum, T. perfasciculatum, and T. subulatum were isolated from the diseased tubers of Gastrodia elata in Yunnan, China. Among the known species, T. hamatum had the highest frequency. T. delicatum belonged to the Koningii clade. T. robustum and T. perfasciculatum were assigned to the Virens clade. T. subulatum emerged as a new member of the Spirale clade. Pathogenicity experiments were conducted on the new species T. robustum, T. delicatum, and T. perfasciculatum, as well as the known species T. hamatum, T. atroviride, and T. harzianum. The infective abilities of different Trichoderma species on G. elata varied, indicating that Trichoderma was a pathogenic fungus causing black rot disease in G. elata.DiscussionThis study provided the morphological characteristics of new species and discussed the morphological differences with phylogenetically proximate species, laying the foundation for research aimed at preventing and managing diseases that affect G. elata.

IntroductionThe unique red blood cell (RBC) properties that characterize the rare neuroacanthocytosis syndromes (NAS) have prompted the exploration of osmotic gradient ektacytometry (Osmoscan) as a diagnostic tool for these disorders. In this exploratory study, we assessed if Osmoscans can discriminate NAS from other neurodegenerative diseases.MethodsA comprehensive assessment was conducted using Osmoscan on a diverse group of patients, including healthy controls (n = 9), neuroacanthocytosis syndrome patients (n = 6, 2 VPS13A and 4 XK disease), Parkinson’s disease patients (n = 6), Huntington’s disease patients (n = 5), and amyotrophic lateral sclerosis patients (n = 4). Concurrently, we collected and analyzed RBC indices and patients’ characteristics.ResultsStatistically significant changes were observed in NAS patients compared to healthy controls and other conditions, specifically in osmolality at minimal elongation index (Omin), maximal elongation index (EImax), the osmolality at half maximal elongation index in the hyperosmotic part of the curve (Ohyper), and the width of the curve close to the osmolality at maximal elongation index (Omax-width).DiscussionThis study represents an initial exploration of RBC properties from NAS patients using osmotic gradient ektacytometry. While specific parameters exhibited differences, only Ohyper and Omax-width yielded 100% specificity for other neurodegenerative diseases. Moreover, unique correlations between Osmoscan parameters and RBC indices in NAS versus controls were identified, such as osmolality at maximal elongation index (Omax) vs. mean cellular hemoglobin content (MCH) and minimal elongation index (EImin) vs. red blood cell distribution width (RDW). Given the limited sample size, further studies are essential to establish diagnostic guidelines based on these findings.

AbstractBackground/Aims Colorectal cancer is the third leading cause of death in patients with cancers in America. Monensin has represented anti-cancer effect on various human cancer cells. We seek to investigate the effect of monensin on proliferation of human colorectal cancer cells and explore whether IGF1R signaling pathway is involved in anti-cancer mechanism of monensin.Methods Cell proliferation and migration were assessed by crystal violet staining and cell wounding assay respectively. Cell apoptosis was analyzed by Hoechst 33258 staining and flow cytometry. Cell cycle progression was detected with the use of flow cytometry. Cancer-associated pathways were assessed with the use of pathway-specific reporters. Gene expression was detected by touchdown-quantitative real-time PCR. Inhibition of IGF1R was tested by immunofluorescence staining. Inhibition of IGF1R signaling was accomplished by adenovirus-mediated expression of IGF1.Results We found that monensin not only effectively inhibited cell proliferation, cell migration as well as cell cycle progression, but also induced apoptosis and G1 arrest in human colorectal cancer cells. Monensin was shown to target multiple cancer-related signaling pathways such as Elk1, AP1, as well as Myc/max, and suppressed IGF1R expression via increasing IGF1 in colorectal cancer cells.Conclusion Monensin could suppressed IGF1R expression via increasing IGF1 in colorectal cancer cells. It has the potential to be repurposed as an anti-colorectal cancer agent, but further studies are still required to investigate the detailed mechanisms of monensin underlying its anti-cancer motion.Key MessagesMonensin inhibits the cell proliferation and the migration, induces apoptosis and inhibits cell cycle progression in human colorectal cancer cells.Monensin may exert anti-cancer activity by targeting multiple signaling pathways, including the IGF1R signaling pathway.Monensin has the potential to be repurposed as an anti-colorectal cancer agent.

With the high intensification of poultry breeding, a series of diseases caused by pathogenic bacteria threaten the health of poultry and human. Among them, poultry diseases induced by Escherichia coli cause significant economic loss every year. The aim of this study was to investigate the effects of dietary supplementation with Artemisia annua L. polysaccharide (AAP) on the growth performance and intestinal barrier function of broilers with Escherichia coli (E. coli) challenge. A total of 256 one-day-old chicks were randomly assigned to four treatment groups: control group (fed basal diet), AAP group (fed basal diet supplemented with AAP), E. coli group (fed basal diet and orally administered E. coli), AAP + E. coli group (fed basal diet supplemented with AAP and orally administered E. coli). Dietary AAP supplementation elevated the BW, ADG and ADFI in non-challenged broilers. AAP also increased the apparent metabolic rate of EE and Ca in E. coli-challenged broilers. Moreover, AAP not only enhanced the serum IgA content but also decreased the serum and jejunum content of IL-6, as well as the jejunum level of IL-1β in non-challenged broilers. AAP also down-regulates the mRNA level of inflammatory factors (IL-1β, IL-6, and TNF-α) by inhibiting the mRNA expression of TLR4 and MyD88 in intestinal NF-κB signaling pathway of E. coli-challenged broilers. Meanwhile, AAP up-regulates the activity and mRNA level CAT by down-regulating the mRNA level of Keap1 in intestinal Nrf2 signaling pathway of E. coli-challenged broilers, and decreased serum MDA concentration. AAP significantly elevated the mRNA level of CAT, SOD and Nrf2 in jejunal of non-challenged broilers. Interestingly, AAP can improve intestinal physical barrier by down-regulating serum ET content, increasing the jejunal villus height/crypt depth (VH/CD) and ZO-1 mRNA level in broilers challenged by E. coli. AAP also elevated the VH/CD and the mRNA level of Occludin, ZO-1, Mucin-2 in non-challenged broilers. Importantly, AAP reshaped the balance of jejunum microbiota in E. coli-challenged broilers by altering α diversity and community composition. In summary, AAP ameliorated the loss of growth performance in broilers challenged with E. coli, probably by regulating the intestinal permeability and mucosa morphology, immune function, antioxidant ability, and microbiota.

Abstract Background Studies have shown that a significant percentage of patients with obstructive sleep apnea (OSA) do not tolerate continuous positive airway pressure (CPAP) therapy and long-term use may be as low as 30%. Given the lower levels of symptoms and health-related risks, patients with mild sleep apnea may be at even higher risk for non-adherence to long term CPAP. The purpose of our study was to investigate the prevalence and associations of long-term CPAP adherence in first time users with mild sleep apnea diagnosed by home sleep apnea testing (HSAT). Methods We identified all the patients who were diagnosed with mild sleep apnea (5 =

Abstract Objective To compute penetrance and recurrence risk using a genome‐wide PRS (including and excluding the APOE region) in families with Alzheimer's disease. Methods Genotypes from the National Institute on Aging Late‐Onset Alzheimer's Disease Family‐Based Study and a study of familial Alzheimer's disease in Caribbean Hispanics were used to compute PRS with and without variants in the 2 MB region flanking APOE. PRS was calculated in using clumping/thresholding and Bayesian methods and was assessed for association with Alzheimer's disease and age at onset. Penetrance and recurrence risk for carriers in highest and lowest PRS quintiles were compared separately within APOE‐ε4 carriers and non‐carriers. Results PRS excluding the APOE region was strongly associated with clinical and neuropathological diagnosis of AD. PRS association with AD was similar in participants who did not carry an APOE‐ε4 allele (OR = 1.74 [1.53–1.91]) compared with APOE‐ε4 carriers (1.53 [1.4–1.68]). Compared to the lowest quintile, the highest PRS quintile had a 10% higher penetrance at age 70 (p = 0.0006) and a 20% higher penetrance at age 80 (p

Decision-making and planning are the core aspects of autonomous driving systems. These factors are crucial for improving the safety, driving experience, and travel efficiency of autonomous vehicles. Intersections are crucial nodes in urban road traffic networks. The objective of this study is to comprehensively review the latest issues and research progress in decision-making and planning for autonomous vehicles in intersection environments. This paper reviews the research progress in the behavioral prediction of traffic participants in terms of machine learning-based behavioral prediction, probabilistic model behavioral prediction, and mixed-method behavioral prediction. Then, behavioral decision-making is divided into reactive decision-making, learning decision-making, and interactive decision-making, each of which is analyzed. Finally, a comparative analysis of motion planning and its applications is performed from a methodological viewpoint, including search, sampling, and numerical methods. First, key issues and major research progress related to end-to-end decision-making and path planning are summarized and analyzed. Second, the impact of decision-making and path planning on the intelligence level of autonomous vehicles in intersecting environments is discussed. Finally, future development trends and technical challenges are outlined.

Rice paddy soil is a hotspot of antibiotic resistance genes (ARGs) due to the application of organic fertilizers. However, the temporal dynamics of ARGs in rice paddy soil and its flooded water during the growing season remain underexplored. In this study, a microcosm experiment was conducted to explore the ARG profiles in a long term (130 days) flooded two-phase manure-amended soil–water system. By using high-throughput quantitative PCR array, a total of 23–98 and 34–85 ARGs were detected in the soil and overlying water, respectively. Regression analysis exhibited significant negative correlations between ARG profile similarities and flooding duration, indicating that flooding significantly altered the resistome (P

Abstract Objective Evaluation of serum neurofilament light chain (sNfL), measured using high‐throughput assays on widely accessible platforms in large, real‐world MS populations, is a critical step for sNfL to be utilized in clinical practice. Methods Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is a network of healthcare institutions in the United States and Europe collecting standardized clinical/imaging data and biospecimens during routine clinic visits. sNfL was measured in 6974 MS and 201 healthy control (HC) participants, using a high‐throughput, scalable immunoassay. Results Elevated sNfL levels for age (sNfL‐E) were found in 1238 MS participants (17.8%). Factors associated with sNfL‐E included male sex, younger age, progressive disease subtype, diabetes mellitus, impaired renal function, and active smoking. Higher body mass index (BMI) was associated with lower odds of elevated sNfL. Active treatment with disease‐modifying therapy was associated with lower odds of sNfL‐E. MS participants with sNfL‐E exhibited worse neurological function (patient‐reported disability, walking speed, manual dexterity, and cognitive processing speed), lower brain parenchymal fraction, and higher T2 lesion volume. Longitudinal analyses revealed accelerated short‐term rates of whole brain atrophy in sNfL‐E participants and higher odds of new T2 lesion development, although both MS participants with or without sNfL‐E exhibited faster rates of whole brain atrophy compared to HC. Findings were consistent in analyses examining age‐normative sNfL Z‐scores as a continuous variable. Interpretation Elevated sNfL is associated with clinical disability, inflammatory disease activity, and whole brain atrophy in MS, but interpretation needs to account for comorbidities including impaired renal function, diabetes, and smoking.

During a survey of soil fungi collected from Yunnan Province, China, two new species of Exophiala, E. yunnanensis and E. yuxiensis, were isolated from the soil of karst rocky desertification (KRD). The DNA sequences of these respective strains, including internal transcribed spacers (ITS), large subunit nuclear ribosomal RNA (LSU rRNA), partial small subunit (SSU) and β-tubulin (tub2) were sequenced and compared with those from species closely-related to Exophiala. Exophiala yunnanensis differs from the phylogenetically closely related E. nagquensis and E. brunnea by its smaller aseptate conidia. Exophiala yuxiensis is phylogenetically related to E. lecanii-corni, E. lavatrina and E. mali, but can be distinguished from them by its larger conidia. Full descriptions, illustrations and phylogenetic positions of E. yunnanensis and E. yuxiensis were provided.

The Gárdos channel (KCNN4) and Piezo1 are the best-known ion channels in the red blood cell (RBC) membrane. Nevertheless, the quantitative electrophysiological behavior of RBCs and its heterogeneity are still not completely understood. Here, we use state-of-the-art biochemical methods to probe for the abundance of the channels in RBCs. Furthermore, we utilize automated patch clamp, based on planar chips, to compare the activity of the two channels in reticulocytes and mature RBCs. In addition to this characterization, we performed membrane potential measurements to demonstrate the effect of channel activity and interplay on the RBC properties. Both the Gárdos channel and Piezo1, albeit their average copy number of activatable channels per cell is in the single-digit range, can be detected through transcriptome analysis of reticulocytes. Proteomics analysis of reticulocytes and mature RBCs could only detect Piezo1 but not the Gárdos channel. Furthermore, they can be reliably measured in the whole-cell configuration of the patch clamp method. While for the Gárdos channel, the activity in terms of ion currents is higher in reticulocytes compared to mature RBCs, for Piezo1, the tendency is the opposite. While the interplay between Piezo1 and Gárdos channel cannot be followed using the patch clamp measurements, it could be proved based on membrane potential measurements in populations of intact RBCs. We discuss the Gárdos channel and Piezo1 abundance, interdependencies and interactions in the context of their proposed physiological and pathophysiological functions, which are the passing of small constrictions, e.g., in the spleen, and their active participation in blood clot formation and thrombosis.

Intestinal cancers are developed from intestinal epithelial stem cells (ISCs) in intestinal crypts through a multi-step process involved in genetic mutations of oncogenes and tumor suppressor genes. ISCs play a key role in maintaining the homeostasis of gut epithelium. In 2009, Sato et al established a three-dimensional culture system, which mimicked the niche microenvironment by employing the niche factors, and successfully grew crypt ISCs into organoids or Mini-guts in vitro. Since then, the intestinal organoid technology has been used to delineate cellular signaling in ISC biology. However, the cultured organoids consist of heterogeneous cell populations, and it was technically challenging to introduce genomic changes into three-dimensional organoids. Thus, there was a technical necessity to develop a two-dimensional ISC culture system for effective genomic manipulations. In this study, we established a conditionally immortalized mouse intestinal crypt (ciMIC) cell line by using a piggyBac transposon-based SV40 T antigen expression system. We showed that the ciMICs maintained long-term proliferative activity under two-dimensional niche factor-containing culture condition, retained the biological characteristics of intestinal epithelial stem cells, and could form intestinal organoids in three-dimensional culture. While in vivo cell implantation tests indicated that the ciMICs were non-tumorigenic, the ciMICs overexpressing oncogenic β-catenin and/or KRAS exhibited high proliferative activity and developed intestinal adenoma-like pathological features in vivo. Collectively, these findings strongly suggested that the engineered ciMICs should be used as a valuable tool cell line to dissect the genetic and/or epigenetic underpinnings of intestinal tumorigenesis.

The family Microthyriaceae is represented by relatively few mycelial cultures and DNA sequences; as a result, the taxonomy and classification of this group of organisms remain poorly understood. During the investigation of the diversity of aquatic hyphomycetes from southern China, several isolates were collected. These isolates were cultured and sequenced and a BLAST search of its LSU sequences against data in GenBank revealed that the closest related taxa are in the genus Microthyrium. Phylogenetic analyses, based on the combined sequence data from the internal transcribed spacers (ITS) and the large subunit (LSU), revealed that these isolates represent eight new taxa in Microthyriaceae, including two new genera, Antidactylaria gen. nov. and Isthmomyces gen. nov. and six new species, Antidactylaria minifimbriata sp. nov., Isthmomyces oxysporus sp. nov., I. dissimilis sp. nov., I. macrosporus sp. nov., Triscelophorus anisopterioideus sp. nov. and T. sinensis sp. nov. These new taxa are described, illustrated for their morphologies and compared with similar taxa. In addition, two new combinations are proposed in this family.

BackgroundApart from bactericidal effects, anti-tuberculosis drugs can interfere with the host’s immune system. In this study, we analyzed the role of delamanid (DLM), an inhibitor of mycolic acid synthesis of mycobacterial cell wall, on human macrophages.MethodsBased on a cohort of multidrug-resistant tuberculosis (MDR-TB) patients treated with DLM, the levels of C-reaction protein (CRP) and cytokines in the plasma were monitored using immunoturbidimetric assay and flow cytometry, respectively. We investigated the role of DLM on CXCL10 expression in U937 cell model using the following methods: cell viability assay, reverse transcription-quantitative polymerase chain reaction, enzyme linked immunosorbent assay, immunoblot, and transwell co-culture assay.ResultsA total of 23 MDR-TB patients were included, comprising of 13 patients treated with optimized background therapeutic regimen (OBR) plus DLM regimen (OBR+DLM) and 10 patients treated with OBR plus placebo. DLM administration was associated with a significant reduce in circulating CRP level. Correspondingly, after treatment, the level of CXCL10 in patients treated with OBR+DLM was significantly lower than that with control. Using cell model, DLM dramatically suppressed CXCL10 expression, which majorly depended on inhibiting the JAK/STAT pathway, and impaired the migration of PBMCs.ConclusionOur data firstly demonstrate that DLM suppresses CXCL10 expression via regulation of JAK2/STAT1 signaling and correlates with reduced inflammation in MDR-TB patients. DLM could be used as a potential drug for immunotherapy of patients with overactive immune response due to CXCL10.

Objective: WFQ-228 is a novel developed fluoroquinolone (FQ) displaying potent antimicrobial activity against various clinical isolates of pathogens, including FQ-resistant isolates. The aim was to comparatively analyze in vitro susceptibilities of WFQ-228, levofloxacin (LFX), and moxifloxacin (MFX) against Mycobacterium tuberculosis (MTB) isolates, especially with gyrA mutations. Methods: We selected a panel of 75 MTB isolates, consisting of 25 FQ-susceptible and 50 FQ-resistant isolates determined by conventional drug susceptibility testing. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of FQs to MTB isolates were assessed. Results: MFX exhibited the most potent activity against FQ-susceptible MTB, demonstrating a MIC50 of 0.031 mg/L, which was lower than that of LFX and WFQ-228. Against FQ-resistant MTB isolates, the MIC50 of WFQ-228 was higher than that of MFX but lower than that of LFX. For WFQ-228, there was a significant overlap existing in the MIC distributions between the probable susceptible (PS) and probable resistant (PR) groups. Six out of 50 PR isolates were classified as susceptible based on a proposed critical concentration (CC) of 0.5 mg/L, yielding a poor sensitivity of 88.0%. These discordant isolates had GyrA substitution in Ala90Val, Ser91Pro, and Asp94Tyr. Additionally, MFX exhibited bactericidal activity against MTB isolates without gyrA mutations, which was significantly higher than that of isolates with gyrA mutations. Conclusion: WFQ-228 is more efficacious than LFX in isolates with specific mutations conferring low-level FQ resistance. The bactericidal effect is noted more frequently in FQ-susceptible isolates than FQ-resistant isolates for MFX.

Members of Plectosphaerella inhabit different substrates, including plants, soil and insects, and most species are pathogens causing large losses in agriculture. During a survey of endophytic fungi in aquatic plants in southwest China, 112 strains of Plectosphaerella were isolated, representing two new species, P. endophytica sp. nov. and P. sichuanensis sp. nov., as well as two known species, P. cucumerina and P. pauciseptata. The novel taxa are described and illustrated here using combined morphological and multi-locus phylogenetic (LSU-ITS-TEF-1α-TUB2) analyses. Our result revealed Plectosphaerella species inhabiting within aquatic plants in southwest China, and the separation frequency of each species was presented.

The species within the family Cunninghamellaceae are widely distributed and produce important metabolites. Morphological studies along with a molecular phylogeny based on the internal transcribed spacer (ITS) and large subunit (LSU) of ribosomal DNA revealed two new species in this family from soils in China, that is, Absidia ovalispora sp. nov. and Cunninghamella globospora sp. nov. The former is phylogenetically closely related to Absidia koreana, but morphologically differs in sporangiospores, sporangia, sporangiophores, columellae, collars, and rhizoids. The latter is phylogenetically closely related to Cunninghamella intermedia, but morphologically differs in sporangiola and colonies. They were described and illustrated.

Deep learning-based salient object detection (SOD) methods have made great progress in recent years. However, most deep learning-based methods suffer from coarse object boundaries and expensive computations, especially in detecting objects with complex shapes. This paper presents an accurate and efficient SOD method that is based on a novel double-branch network that includes a body branch and an edge branch. To obtain an accurate edge, an edge profile enhancement module (EPEM) is embedded in the edge branch. In addition, a fusion feedback module (FFM) is embedded to integrate features from the two branches. To address the problem of expensive computations, channel attention module (CAM) is included to restrain redundant feature channels. Thus, the speed of the inference step can be improved with little reduction in the boundary accuracy. Experimental results on 9 datasets demonstrate that the proposed method performs favorably against 8 state-of-the-art methods in terms of both accuracy and efficiency. Additionally, our method achieves excellent detection results for objects with complex shapes.

ObjectivesIn this study, we conducted a systematic review to determine tuberculosis (TB) incidence due to immunotherapy with programmed cell death protein-1 (PD-1)/PD ligand (PD-L1) blockade in cancer patients.MethodsWe searched PubMed, Cochrance Library, Excerpt Medica Database (Embase), ClinicalTrials.gov, Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure Database (CNKI), Wanfang and China Science and Technology Journal Database to identify studies between January 1, 2000 and April 30, 2021, on the reports of TB cases in patients treated with PD-1/PD-L1 blockade. Methodological quality of eligible studies was assessed, and random-effect model meta-analysis was performed to generate the pooled incidence estimate of TB cases in patients undergoing PD-1/PD-L1 therapy.ResultsWe initially identified 745 records, of which 27 studies ultimately met the inclusion criteria and were included in our meta-analysis. A total of 35 TB cases occurred among patients treated with PD-1/PD-L1 blockade. Nivolumab (51.4%) was the most frequently used PD-1/PD-L1 blockade for cancer treatment. In addition, pulmonary TB was the most common form of tuberculosis seen in 77.1% cases. Clinical outcomes were recorded in 18 patients, of whom 77.8% were cured or achieved remission, and 22.2% were died of TB. Pooled analysis determined that the TB rate in this population was 2,000 cases per 100,000 persons, and the estimated rate for TB associated with PD-1/PD-L1 blockade was 35 times higher than that in the general population.ConclusionTo conclude, our results demonstrate that the clinical use of PD-1/PD-L1 inhibitors significantly increases risk of TB reactivation. An extremely high mortality rate due to TB disease is noted in the patients with PD-1/PD-L1 blockade.

Long-term fertilization is known to impact the biodiversity and community structures of soil organisms, which are responsible for multiple soil ecosystem functions (multifunctionality). However the relationship between the alterations of soil organisms and ecosystem multifunctionality remains unclear, especially in the case of long-term fertilization. To explore the contribution of soil organismal biodiversity and community structures to ecosystem multifunctionality, we took soil samples from a nearly 25-year field fertilization experiment. Organic matter significantly improved the soil ecosystem multifunctionality. Ecosystem multifunctionality was found to be closely linked to the biodiversity and communities of soil organisms within the major ecological clustering of soil organisms (Module 1) according to the trophic co-occurrence network, rather than the entire community of soil organisms. This indicated that ecological clusters of soil organisms within the network were critical in maintaining soil ecosystem multifunctionality. The application of organic fertilization could enrich specialized soil organisms and increase interactions of soil organisms in the ecological cluster. As a result, our findings emphasize the role of ecological clusters in the soil organismal co-occurrence network in controlling soil multifunctionality after long-term fertilization, presenting a novel perspective on the link between soil biodiversity and ecosystem multifunctionality.

During a mycological survey of aquatic hyphomycetes on submerged decaying leaves in southwest China, a distinct new fungus was collected. The collection was cultured and sequenced and a BLAST search of its ITS and LSU sequence against data in GenBank revealed a dothideomycetous affiliation, with the closest related taxa in the genus Neodactylaria. Phylogenetic analyses of a multigene matrix containing sequences from four genes (LSU, SSU, rpb2, and tef1), representing broad groups of Dothideomycetes, revealed its placement within Dothideomycetes, but without a supported familial or ordinal affiliation. Based on further phylogenetic analyses and morphological investigations, the new fungus is described here as a new species of Neodactylaria, N. simaoensis sp. nov., and placed in a new family Neodactylariaceae fam. nov. and a new order Neodactylariales ord. nov.

Organic rheology modifiers, especially superplasticizers and viscosity-modifying admixtures (VMAs), have become key components for the workability optimization of modern concrete. The development of these admixtures is crucial to the further performance improvement of modern concrete under different casting and service conditions. Many of the former reviews have summarized research advances in respect of these admixtures from chemical and material perspectives, focusing on the effects of structure and the performance. In this paper, from a rheological perspective, an overview is provided of the microscale behavior of polycarboxylate (PCE) superplasticizers and VMAs (e.g., adsorption, conformation, and bridging) in terms of the evolution of the microstructure of the paste, the effect of chemical structure on the yield stress, the apparent viscosity and thixotropy of cement-based materials, and the structure design of these admixtures. Most importantly, in addition to a general discussion with assumptions (monolayer adsorption of a “flat” conformation, with each molecule on a single particle; statistical polymer composition), special conditions (e.g., preferential adsorption, depletion effects, hydration modification effects, and the polydispersity of the polymer composition) are discussed. Newly developed admixtures, realized through regulation of the microscale behavior, and by the modification of adsorption, topological structure, and molecular frame, are introduced.

Recently, the development of composite materials composed of magnetic materials and MXene has attracted significant attention. However, the thickness and microwave absorption performance of the composite is still barely satisfactory. In this work, the C-N@NiFe2O4@MXene/Ni nanocomposites were successfully synthesized in situ by hydrothermal and calcination methods. Benefiting from the introduction of the carbon-nitrogen(C-N) network structure, the overall dielectric properties are improved effectively, consequently reducing the thickness of the composite while maintaining excellent absorption performance. As a result, the minimum reflection loss of C-N@NiFe2O4@MXene/Ni can reach −50.51 dB at 17.3 GHz at an ultralow thickness of 1.5 mm, with an effective absorption bandwidth of 4.95 GHz (13.02–18 GHz). This research provides a novel strategy for materials to maintain good absorption performance at an ultralow thickness level.

Excess large and unstable air bubbles can reduce the compressive strength of hardened concrete, and traditional defoamers always fail because of adsorption and encapsulation on cement with the progress of cement hydration in later stages. It is necessary to develop a novel defoamer that shows a sustained defoaming ability in fresh concrete. A novel slow-release defoamer for concrete using porous nanoparticles as carriers is reported for the first time. The porous nanoparticles/polyether defoamer composite (SiO2-Def) was prepared via sol-gel method. SiO2-Def is a spherical composite nanoparticle with a size range of 160–200 nm and a uniform pore size distribution. SiO2-Def shows a high load rate of about 16.4% and an excellent release under an alkali and salt environment. It has a weak initial defoaming ability but shows a sustained defoaming ability with time, so that it can avoid the failures of defoamers and eliminate harmful bubbles entrained during the processes of pumping and transportation. Moreover, SiO2-Def produced a higher compressive strength of the hardened cement mortars.

In this study, a series of polyether-type defoamers for concrete which consist of the same alkyl chain (hydrophobic part) but different polyether chains (hydrophilic part) was prepared, and the structure–property relationship of the defoamers was investigated for the first time. Using oleyl alcohol (OA) as the starting agent (alkyl chain), the polyether defoamers with different polyether chains were prepared by changing the amount and sequence of ethylene oxide (EO) and propylene oxide (PO) units. The properties of different defoamers were tested in aqueous solutions, and fresh and hardened mortars; the structure–property relationship of the defoamers was thus studied. The results indicated that the defoaming capacity of the polyether defoamers decreased with an increased EO amount, and the defoamers linked with both EO and PO units (PO before EO) had a stronger defoaming capacity than those linked with EO only. This study is beneficial for the development and applications of novel synthetic polyether-type defoamers for concrete.

Self-compacting concrete (SCC) is an extremely flowable concrete, which increases the probability of segregation and bleeding. Viscosity-modifying admixtures (VMAs) have been developed to improve the stability of SCC. Synthetic polymer VMAs have excellent water solubility and stability, and can be easily chemically prepared and modified. In this work, a series of copolymers based on anionic 2-acrylamido-2-methyl-propanesulfonic acid (AMPS) and nonionic N, N-dimethyl acrylamide (DMAA), with similar molecular weights but different charge densities, were prepared. The effect of the charge density of the anionic polymers on the fluidity, rheological property, and adsorption behavior of the cement pastes was investigated. The action mechanism of the polymers was discussed. The results indicate that the charge density of anionic polymer VMAs is of great significance for the development of cost-effective SCCs with good rheological properties.

Fluoride-containing alkali-free setting accelerators are a common type of admixture used in tunnel shotcrete but few studies in the literature focus on the effect of their fluoride compounds on the setting and hardening properties of accelerated cement paste under low environment temperatures. Tunnel shotcrete in cold regions or winter construction periods would be obviously influenced by low environment temperatures, especially for its fast setting and quick support applications. The objective of this work is to evaluate the early age hydration behavior of different accelerated cement pastes under 20 °C and 5 °C environment temperatures. In this study, setting time measurement, early age strength development, hydration ion leaching concentration, isothermal calorimetry, X-ray diffraction, and ESEM were performed on cement systems prepared with a non-fluoride alkali-free accelerator (aluminum sulfate solution with over 60% solid content) and a designed fluoride-containing alkali-free setting accelerator (aluminum sulfate and fluoride compound). The results showed that the fluorides obtained in alkali-free accelerators promote C3S dissolution and massive ettringite needles together with monosulfoaluminate (AFm) hydrate formation, thus leading to a quicker setting effect and low sensitivity to low environment temperatures than in non- fluoride groups. However, the rate of mechanical strength development of cement pastes hydrated within 24 h was decreased obviously when fluorine-containing alkali-free accelerator was used. This phenomenon is mainly related to the crystallization of thin-plate shape calcium fluoride (CaF2) formations and promoted conversion of ettringite to monosulfoaluminate hydrate in the accelerating period, thus weakening the denseness of C-S-H gel and inhibiting alite further hydration.

Aquatic ecosystems contain tremendous plant and microbial diversity. However, little is known about endophyte diversity in aquatic plants. In this study, we investigated the diversity of endophytic fungi in aquatic plants in southwest China using both culture-based and culture-independent high-throughput sequencing methods. A total of 1,689 fungal isolates belonging to three phyla and 154 genera were obtained from 15,373 plant tissue segments of 30 aquatic plant species. The most abundant endophytic fungi were those in ascomycete genera Aspergillus, Ceratophoma, Fusarium, Penicillium, Phoma and Plectosporium. No difference in fungal isolation rates was observed among tissues from roots, stems, and leaves. Twenty tissue samples from three most common plant species were further subjected to culture-independent meta-barcode sequencing. The sequence-based analyses revealed a total of 1,074 OTUs belonging to six fungal phyla and 194 genera. Among the three plants, Batrachium bungei harbored the highest number of OTUs. Besides, a total of 66 genera were detected by two methods. Both the culture-dependent and independent methods revealed that aquatic plants in southwest China have abundant endophytic fungal diversity. This study significantly expands our knowledge of the fungal community of aquatic plants.

Two new species of the genus Verruconis, V. hainanensis and V. pseudotricladiata, were described using combined morphological and DNA sequence data. The DNA sequences of respective strains including nuclear ribosomal DNA genes (nuSSU, ITS, nuLSU) and fragments of three protein-coding genes (ACT1, BT2, TEF1) were sequenced and compared with those from closely-related species to genera Ochroconis and Verruconis (Family Sympoventuriaceae, Order Venturiales). Morphologically, both species showed typical ampulliform conidiophores and conidiogenous cells, features not seen in other species of Verruconis. The conidia of V. hainanensis are fusiform and those of V. pseudotricladiata are Y or T shaped, similar to old members of a closely-related genus Scolecobasidium. The addition of these two new species provides a new perspective on the heterogeneity of Scolecobasidium.

Reasonable structural design and composition control are the dominant factors for tuning the electromagnetic absorbing properties of materials. In this paper, microspheres composed of NiO, Ni, and Co3O4 nanoparticles (NCMO) were successfully synthesized using a mild oxidation method. Benefiting from the multi-component composition and a unique microstructure, the RLmin of CNMO can reach −46.8 dB at 17 GHz, with an effective absorption bandwidth of 4.1 GHz (13.9–18 GHz). The absorbing properties and the absorbing mechanism analysis showed that the microsphere-structured NCMO composed of multi-component nanoparticles enhanced the interface polarization, thereby improving the absorption performance. This research provides a new avenue for MOF-derived oxide materials with excellent electromagnetic wave absorbing properties.

Fungi in the genus Trichoderma are widely distributed in China, including in Yunnan province. In this study, we report three new soil-inhabiting species in Trichoderma, named as T. kunmingense, T. speciosum and T. zeloharzianum. Their colony and mycelial morphology, including features of asexual states, were described. For each species, their DNA sequences were obtained from three loci, the internal transcribed spacer (ITS) regions of the ribosomal DNA, the translation elongation factor 1-α encoding gene (tef1) and the gene encoding the second largest nuclear RNA polymerase subunit (rpb2). Our analyses indicated that the three new species showed consistent divergence amongst each other and from other known and closely related species. Amongst the three, T. speciosum and T. kunmingense belong to the Viride Clade. Specifically, T. speciosum is related to three species – T. hispanicum, T. samuelsii and T. junci and is characterised by tree-like conidiophores, generally paired branches, curved terminal branches, spindly to fusiform phialides and subglobose to globose conidia. In contrast, T. kunmingense morphologically resembles T. asperellum and T. yunnanense and is distinguished by its pyramidal conidiophores, ampulliform to tapered phialides, discrete branches and ovoidal, occasionally ellipsoid, smooth-walled conidia. The third new species, T. zeloharzianum, is a new member of the Harzianum Clade and is closely associated with T. harzianum, T. lixii and T. simmonsii but distinguished from them by having smaller, subglobose to globose, thin-walled conidia.

Manure, which contains large amounts of antibiotics and antibiotic resistance genes (ARGs), is widely used in agricultural soils and may lead to the evolution and dispersal of ARGs in the soil environment. In the present study, soils that received manure or chemical fertilizers for 15 years were sampled on the North China Plain (NCP), which is one of the primary areas of intensive agriculture in China. High-throughput quantitative PCR and sequencing technologies were employed to assess the effects of long-term manure or chemical fertilizer application on the distribution of ARGs and microbial communities. A total of 114 unique ARGs were successfully amplified from all soil samples. Manure application markedly increased the relative abundance and detectable numbers of ARGs, with up to 0.23 copies/16S rRNA gene and 81 unique ARGs. The increased abundance of ARGs in manure-fertilized soil was mainly due to the manure increasing the abundance of indigenous soil ARGs. In contrast, chemical fertilizers only moderately affected the diversity of ARGs and had no significant effect on the relative abundance of the total ARGs. In addition, manure application increased the abundance of mobile genetic elements (MGEs), which were significantly and positively correlated with most types of ARGs, indicating that horizontal gene transfer via MGEs may play an important role in the spread of ARGs. Furthermore, the application of manure and chemical fertilizers significantly affected microbial community structure, and variation partitioning analysis showed that microbial community shifts represented the major driver shaping the antibiotic resistome. Taken together, our results provide insight into the long-term effects of manure and chemical fertilization on the dissemination of ARGs in intensive agricultural ecosystems.

Ageratina adenophora is one of the most invasive weeds in China. Following an outbreak in Yunnan in the 1960s, A. adenophora has been spreading in Southwest China at tremendous speed. Previous research indicated A. adenophora contained many Colletotrichum species as endophytes. In this study, we investigated the diversity of Colletotrichum in healthy and diseased leaves of the invasive plant A. adenophora and several surrounding crops in Yunnan, Guangxi, and Guizhou provinces in China, and obtained over 1000 Colletotrichum strains. After preliminary delimitation using the internal transcribed spacer region (ITS) sequences, 44 representative strains were selected for further study. Their phylogenetic positions were determined by phylogenetic analyses using combined sequences of ITS, actin (ACT), chitin synthase (CHS-1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and beta-tubulin (TUB2). Combined with morphological characteristics, 14 new Colletotrichum species were named as C. adenophorae, C. analogum, C. cangyuanense, C. dimorphum, C. gracile, C. nanhuaense, C. nullisetosum, C. oblongisporum, C. parvisporum, C. robustum, C. simulanticitri, C. speciosum, C. subhenanense, and C. yunajiangense.

Colletotrichum species are plant pathogens, saprobes, and endophytes in many economically important hosts. Many studies have investigated the diversity and pathogenicity of Colletotrichum species in common ornamentals, fruits, and vegetables. However, Colletotrichum species occurring in aquatic plants are not well known. During the investigation of the diversity of endophytic fungi in aquatic plants in southwest China, 66 Colletotrichum isolates were obtained from aquatic plants there, and 26 of them were selected for sequencing and analyses of actin (ACT), chitin synthase (CHS-1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the internal transcribed spacer (ITS) region, and β-tubulin (TUB2) genomic regions. Based on morphological characterization and multi-locus phylogenetic analyses, 13 Colletotrichum species were recognized, namely, C. baiyuense sp. nov., C. casaense sp. nov., C. demersi sp. nov., C. dianense sp. nov., C. fructicola, C. garzense sp. nov., C. jiangxiense, C. karstii, C. philoxeroidis sp. nov., C. spicati sp. nov., C. tengchongense sp. nov., C. vulgaris sp. nov., C. wuxuhaiense sp. nov. Two species complexes, the C. boninense species complex and C. gloeosporioides species complex, were found to be associated with aquatic plants. Pathogenicity tests revealed a broad diversity in pathogenicity and aggressiveness among the eight new Colletotrichum species.

Classicula sinensis, isolated from decaying leaves from Mozigou, Chongqing Municipality, China, is described as a new species. The new species is a member of basidiomycetous aquatic hyphomycetes which represent a small proportion of all aquatic hyphomycetes. This species falls within the genus Classicula (Classiculaceae, Pucciniomycotina) and is closely related to C. fluitans, based on multiple gene sequence analyses. Morphologically, it is characterised by the apical, hyaline, obclavate or navicular conidia with several hair-like lateral appendages and by its holoblastic and monoblastic conidiogenesis, with a flat un-thickened conidiogenous locus. Clamp connections and haustorial branches were often observed in culture.

Background/Aims: Periodontitis is a prevalent chronic inflammatory disease caused by enhanced inflammation induced by dysbiotic microbes forming on subgingival tooth sites, which may disturb the balance of the microbial composition in the biofilm and finally result in the progressive destruction of the periodontal ligament and alveolar bone with periodontal pocket formation and/or gingival recession. Methods: To elucidate the correlation between subgingival microbiome and IgAN incidence in CP (chronic periodontitis at severe levels) patients, subgingival plaque samples were collected from CP patients without IgAN (Control) and CP patients with IgAN (Disease). 16S rRNA sequencing and comparative analyses of plaque bacterial microbiome between Control and Disease were performed. Results: Subgingival microbial diversity in Disease was a little higher than that in Control. Besides, significant differences were found in subgingival microbiome between Disease and Control. Compared with that in Control, at phylum level, the abundances of Proteobacteria and Actinobacteria were significantly higher while the abundances of Bacteroidetes, Fusobacteria, Spirochaetae, Synergistetes, and Saccharibacteria were significantly lower in Disease; at class level, the abundances of Betaproteobacteria, Bacilli, Actinobacteria, Flavobacteriia, and Gammaproteobacteria were significantly higher while the abundances of Bacteroidia, Fusobacteriia, Negativicutes, Clostridia, and Spirochaetes were significantly lower in Disease; at genus level, the abundances of Bergeyella, Capnocytophaga, Actinomyces, Corynebacterium, Comamonas, Lautropia, and Streptococcus were significantly higher while the abundances of Treponema and Prevotella were significantly lower in Disease. Conclusions: Our data indicated a correlation between the changes in subgingival microbial structure and IgAN incidence in CP patients, which might be used to predict IgAN incidence in CP patients.

Pancreatic beta cell dysfunction caused by metabolic and inflammatory stress contributes to the development of type 2 diabetes (T2D). Butyrate, produced by the gut microbiota, has shown beneficial effects on glucose metabolism in animals and humans and may directly affect beta cell function, but the mechanisms are poorly described. The aim of this study was to investigate the effect of butyrate on cytokine-induced beta cell dysfunction in vitro. Mouse islets, rat INS-1E, and human EndoC-βH1 beta cells were exposed long-term to non-cytotoxic concentrations of cytokines and/or butyrate to resemble the slow onset of inflammation in T2D. Beta cell function was assessed by glucose-stimulated insulin secretion (GSIS), gene expression by qPCR and RNA-sequencing, and proliferation by incorporation of EdU into newly synthesized DNA. Butyrate protected beta cells from cytokine-induced impairment of GSIS and insulin content in the three beta cell models. Beta cell proliferation was reduced by both cytokines and butyrate. Expressions of the beta cell specific genes Ins, MafA, and Ucn3 reduced by the cytokine IL-1β were not affected by butyrate. In contrast, butyrate upregulated the expression of secretion/transport-related genes and downregulated inflammatory genes induced by IL-1β in mouse islets. In summary, butyrate prevents pro-inflammatory cytokine-induced beta cell dysfunction.

A new species, Colletotrichum menglaense, isolated from air in Mengla, Xishuangbanna, Yunnan Province, China, was characterized and described combining morphological characteristics and multigene phylogenetic analysis. Morphologically, it is characterized by oblong, sometimes slightly constricted, micro-guttulate conidia and simple obovoid to ellipsoidal appressoria. Phylogenetic analysis of the ITS, ACT, CHS, and GAPDH sequences showed that C. menglaense belongs to the C. gloeosporioides complex. The pathogenicity of C. menglaense on fruits of several crop plants, including strawberry, orange, grape, tomato, and blueberry, was tested and confirmed by the re-isolation of C. menglaense.

During the investigation of endophytic fungi diversity in aquatic plants and the fungal diversity in soil in southwest China, we obtained 208 isolates belonging to Trichoderma, including 28 isolates as endophytes from aquatic plants and 180 isolates as saprobes from soil, respectively. Finally, 23 new species of Trichoderma are recognized by further studies. Their phylogenetic positions are determined by sequence analyses of the combined partial sequences of translation elongation factor 1-alpha (tef1) and gene encoding of the second largest nuclear RNA polymerase subunit (rpb2). The results revealed that the 23 new species are distributed in nine known clades. The morphology and culture characteristics are observed, described and illustrated in detail. Distinctions between the new species and their close relatives were compared and discussed. These include: Trichoderma achlamydosporum, T. amoenum, T. anaharzianum, T. anisohamatum, T. aquatica, T. asiaticum, T. asymmetricum, T. inaequilaterale, T. inconspicuum, T. insigne, T. obovatum, T. paraviride, T. pluripenicillatum, T. propepolypori, T. pseudoasiaticum, T. pseudoasperelloides, T. scorpioideum, T. simile, T. subazureum, T. subuliforme, T. supraverticillatum, T. tibetica, and T. uncinatum.

Gastrodia elata is a well-known medicinal and heterotrophic orchid. Its germination, limited by the impermeability of seed coat lignin and inhibition by abscisic acid (ABA), is triggered by symbiosis with fungi such as Mycena spp. However, the molecular mechanisms of lignin degradation by Mycena and ABA biosynthesis and signaling in G. elata remain unclear. In order to gain insights into these two processes, this study analyzed the transcriptomes of these organisms during their dynamic symbiosis. Among the 25 lignin-modifying enzyme genes in Mycena, two ligninolytic class II peroxidases and two laccases were significantly upregulated, most likely enabling Mycena hyphae to break through the lignin seed coats of G. elata. Genes related to reduced virulence and loss of pathogenicity in Mycena accounted for more than half of annotated genes, presumably contributing to symbiosis. After coculture, upregulated genes outnumbered downregulated genes in G. elata seeds, suggesting slightly increased biological activity, while Mycena hyphae had fewer upregulated than downregulated genes, indicating decreased biological activity. ABA biosynthesis in G. elata was reduced by the downregulated expression of 9-cis-epoxycarotenoid dioxygenase (NCED-2), and ABA signaling was blocked by the downregulated expression of a receptor protein (PYL12-like). This is the first report to describe the role of NCED-2 and PYL12-like in breaking G. elata seed dormancy by reducing the synthesis and blocking the signaling of the germination inhibitor ABA. This study provides a theoretical basis for screening germination fungi to identify effective symbionts and for reducing ABA inhibition of G. elata seed germination.

Circuit-specific signaling of ventral tegmental area (VTA) dopamine neurons drives different aspects of motivated behavior, but the neuromodulatory control of these circuits is unclear. We tested the actions of co-expressed lateral hypothalamic peptides, orexin A (oxA) and dynorphin (dyn), on projection-target-defined dopamine neurons in mice. We determined that VTA dopamine neurons that project to the nucleus accumbens lateral shell (lAcbSh), medial shell (mAcbSh), and basolateral amygdala (BLA) are largely non-overlapping cell populations with different electrophysiological properties. Moreover, the neuromodulatory effects of oxA and dyn on these three projections differed. OxA selectively increased firing in lAcbSh- and mAcbSh-projecting dopamine neurons. Dyn decreased firing in the majority of mAcbSh- and BLA-projecting dopamine neurons but reduced firing only in a small fraction of those that project to the lAcbSh. In conclusion, the oxA-dyn input to the VTA may drive reward-seeking behavior by tuning dopaminergic output in a projection-target-dependent manner.

Background/Aims: Ovarian cancer is the most lethal gynecologic malignancy, and there is an unmet clinical need to develop new therapies. Although showing promising anticancer activity, Niclosamide may not be used as a monotherapy. We seek to investigate whether inhibiting IGF signaling potentiates Niclosamide's anticancer efficacy in human ovarian cancer cells. Methods: Cell proliferation and migration are assessed. Cell cycle progression and apoptosis are analyzed by flow cytometry. Inhibition of IGF signaling is accomplished by adenovirus-mediated expression of siRNAs targeting IGF-1R. Cancer-associated pathways are assessed using pathway-specific reporters. Subcutaneous xenograft model is used to determine anticancer activity. Results: We find that Niclosamide is highly effective on inhibiting cell proliferation, cell migration, and cell cycle progression, and inducing apoptosis in human ovarian cancer cells, possibly by targeting multiple signaling pathways involved in ELK1/SRF, AP-1, MYC/MAX and NFkB. Silencing IGF-1R exert a similar but weaker effect than that of Niclosamide's. However, silencing IGF-1R significantly sensitizes ovarian cancer cells to Niclosamide-induced anti-proliferative and anticancer activities both in vitro and in vivo. Conclusion: Niclosamide as a repurposed anticancer agent may be more efficacious when combined with agents that target other signaling pathways such as IGF signaling in the treatment of human cancers including ovarian cancer.

Yunnan pine is the most important tree species in SW China in both economical and ecological terms, but it is often killed by pine shoot beetles (Tomicus spp.). Tomicus beetles are secondary pests in temperate regions and the aggressiveness of the beetles in SW China is considered to be due to the warm subtropical climates as well as the beetles’ virulent fungal associates. Here, we assessed the virulence of three blue-stain fungi (Leptographium wushanense, L. sinense and Ophiostoma canum) associated with pine shoot beetles to Yunnan pine (Pinus yunnanensis) in SW China. Following fungal inoculation, we measured necrotic lesion lengths, antioxidant enzyme activities and monoterpene concentrations in the stem phloem of Yunnan pine. Leptographium wushanense induced twice as long lesions as L. sinense and O. canum, and all three fungi induced significantly longer lesions than sterile agar control inoculations. The activity of three tested antioxidant enzymes (peroxidase, polyphenol oxidase, and superoxide dismutase) increased after both fungal inoculation and control inoculation. However, L. wushanense and L. sinense generally caused a greater increase in enzyme activities than O. canum and the control treatment. Fungal inoculation induced stronger increases in six major monoterpenes than the control treatment, but the difference was significant only for some fungus-monoterpene combinations. Overall, our results show that L. wushanense and L. sinense elicit stronger defense responses and thus are more virulent to Yunnan pine than O. canum. The two Leptographium species may thus contribute to the aggressiveness of their beetle vectors and could damage Yunnan pine across SW China if they spread from the restricted geographical area they have been found in so far.

Background/Aims: Liver is a vital organ and retains its regeneration capability throughout adulthood, which requires contributions from different cell populations, including liver precursors and intrahepatic stem cells. To overcome the mortality of hepatic progenitors (iHPs) in vitro, we aim to establish reversibly immortalized hepatic progenitor cells from mouse embryonic liver. Methods and Results: Using retroviral system to stably express SV40 T antigen flanked with Cre/LoxP sites, we establish a repertoire of iHP clones with varied differentiation potential. The iHP cells maintain long-term proliferative activity and express varied levels of progenitor markers (Pou5f1/Oct4 and Dlk) and hepatocyte markers (AFP, Alb and ApoB). Five representative iHP clones express hepatic/pancreatic transcription factors HNF3α/Foxa1, HNF3β/Foxa2, and HNF4α/MODY1. Dexamethasone is shown to promote the expression of hepatocyte markers AFP and TAT, along with ICG-uptake and glycogen storage functions in the iHP clones. Cre-mediated removal of SV40 T antigen reverses the proliferative activity of iHP cells. When iHP cells are subcutaneously implanted in athymic nude mice, no tumor formation is observed for up to 8 weeks. Conclusions: We demonstrate that the established iHP cells are stable, reversible, and non-tumorigenic hepatic progenitor-like cells, which should be valuable for studying liver organogenesis, metabolic regulations, and hepatic lineage-specific differentiation.

Ischemically damaged brain can be accompanied by secondary degeneration of associated axonal connections e.g. Wallerian degeneration. Diffusion tensor imaging (DTI) is widely used to investigate axonal injury but the cellular correlates of many of the degenerative changes remain speculative. We investigated the relationship of DTI of directly damaged cerebral cortex and secondary axonal degeneration in the cerebral peduncle with cellular alterations in pan-axonal neurofilament staining, myelination, reactive astrocytes, activation of microglia/macrophages and neuronal cell death. DTI measures (axial, radial and mean diffusivity, and fractional anisotropy (FA)) were acquired at hyperacute (3 h), acute (1 and 2 d) and chronic (1 and 4 week) times after transient cerebral hypoxia with unilateral ischemia in neonatal rats. The tissue pathology underlying ischemic and degenerative responses had a complex relationship with DTI parameters. DTI changes at hyperacute and subacute times were smaller in magnitude and tended to be transient and/or delayed in cerebral peduncle compared to cerebral cortex. In cerebral peduncle by 1 d post-insult, there were reductions in neurofilament staining corresponding with decreases in parallel diffusivity which were more sensitive than mean diffusivity in detecting axonal changes. Ipsilesional reductions in FA within cerebral peduncle were robust in detecting both early and chronic degenerative responses. At one or four weeks post-insult, radial diffusivity was increased ipsilaterally in the cerebral peduncle corresponding to pathological evidence of a lack of ontogenic myelination in this region. The detailed differences in progression and magnitude of DTI and histological changes reported provide a reference for identifying the potential contribution of various cellular responses to FA, and, parallel, radial, and mean diffusivity.

Using maltodextrin (MD) of different dextrose equivalent (DE) values, 1,3-propanesultone, and maleic anhydride as raw materials, a novel binary modified maltodextrin (BMMD) was synthesized and further applied as a water-reducing agent. Its structure was characterized by Fourier transform infrared (FT-IR) and UV. The rheological behavior of the sample solution and strengths for concrete were also determined and the adsorption was tested by TOC. The influence of the process parameters to degree of substitution (DS) and the dosage on the fluidity of cement paste were investigated. The results show that the optimal conditions of sulfonation were the MD of DE 15, m (sulfonated agent)/m (MD) of 1.4, the catalyst amount of 1% by mass MD, and the reaction time of 12 h; the optimal conditions of esterification were m (esterified agent)/m (SMD) of 0.6, the reaction temperature of 90°C, and the reaction time of 4 h. The optimal dosages of sulfonated maltodextrin (SMD) and BMMD were 0.475% and 0.45%, respectively. In this dosage, the main dispersion capacity of BMMD attributes to two kinds of anchoring groups (SO3- & COO-) and the appropriate molecular weight of MD.