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Abstract Background The symbiosis between arbuscular mycorrhizal fungi (AMF) and plants often stimulates plant growth, increases agricultural yield, reduces costs, thereby providing significant economic benefits. AMF can also benefit plants through affecting the rhizosphere microbial community, but the underlying mechanisms remain unclear. Using Rhizophagus intraradices as a model AMF species, we assessed how AMF influences the bacterial composition and functional diversity through 16 S rRNA gene sequencing and non-targeted metabolomics analysis in the rhizosphere of aluminum-sensitive soybean that were inoculated with pathogenic fungus Nigrospora oryzae and phosphorus-solubilizing fungus Talaromyces verruculosus in an acidic soil. Results The inoculation of R. intraradices, N. oryzae and T. verruculosus didn’t have a significant influence on the levels of soil C, N, and P, or various plant characteristics such as seed weight, crude fat and protein content. However, their inoculation affected the structure, function and nutrient dynamics of the resident bacterial community. The co-inoculation of T. verruculosus and R. intraradices increased the relative abundance of Pseudomonas psychrotolerans, which was capable of N-fixing and was related to cry-for-help theory (plants signal for beneficial microbes when under stress), within the rhizosphere. R. intraradices increased the expression of metabolic pathways associated with the synthesis of unsaturated fatty acids, which was known to enhance plant resistance under adverse environmental conditions. The inoculation of N. oryzae stimulated the stress response inside the soil environment by enriching the polyene macrolide antifungal antibiotic-producing bacterial genus Streptomyces in the root endosphere and upregulating two antibacterial activity metabolic pathways associated with steroid biosynthesis pathways in the rhizosphere. Although inoculation of pathogenic fungus N. oryzae enriched Bradyrhizobium and increased soil urease activity, it had no significant effects on biomass and N content of soybean. Lastly, the host niches exhibited differences in the composition of the bacterial community, with most N-fixing bacteria accumulating in the endosphere and Rhizobium vallis only detected in the endosphere. Conclusions Our findings demonstrate that intricate interactions between AMF, associated core fungi, and the soybean root-associated ecological niches co-mediate the regulation of soybean growth, the dynamics of rhizosphere soil nutrients, and the composition, function, and metabolisms of the root-associated microbiome in an acidic soil.

Compared to the middle and shallow strata, the engineering geological characteristics of Weirong deep shale gas are more complex, with the four characteristics of high ground stress, high horizontal stress difference, high plasticity, and high formation pressure. The complex engineering geological characteristics bring three major challenges: difficulty in forming complex fracture networks, difficulty in supporting and maintaining artificial fractures, and frequent occurrence of abnormal situations such as casing deformation. The specific performance result is the low single well EUR after gas well fracturing. Through unremitting exploration and practice, the fracturing technology has been continuously improved in the process of discovering and solving problems, and a series of measures of "fine optimization, real-time warning, operating pace control, and W-shaped well network" for preventing casing deformation and increasing post fracturing output has been formed based on the concept of balanced fracturing. The technology has been promoted and applied in 39 wells, and the fracturing effect has been continuously improved, with an average EUR increase of 500×104 m3 per well, and a decrease of casing deformation rate from 42.4% in 2022 to 16.67% at present. Due to the impact of the production of adjacent old wells on the production of newly fractured production wells, the output of new wells after fracturing is lower than the previous stage. With the existing well spacing of 400 m (Phase Ⅰ)/300 m (Phase Ⅱ), there is room for reduction and optimization in fracturing scale. Subsequent new wells should be differentiated and optimized based on remaining reserves, and research on fracturing technology shall be carried out continuously, achieving the beneficial development of Weirong deep shale gas.

Abstract Background Cognitive reserve (CR) has been linked to dementia, yet its influence on the risk of depression and related outcomes remains unknown. We aimed to examine the association of CR with depression and subsequent dementia or death, and to assess the extent to which CR is related to depression-free survival. Methods Within the UK Biobank, 436,232 participants free of depression and dementia were followed. A comprehensive CR indicator (low, moderate, and high) was created using latent class analysis based on information on education, occupation, mentally passive sedentary behavior, social connection, confiding with others, and leisure activities. Depression, dementia, and survival status were ascertained through self-reported medical history and/or linkages to medical records. Data were analyzed using multi-state Markov model and Laplace regression. Results Over a median follow-up of 12.96 years, 16,560 individuals developed depression (including 617 with subsequent dementia) and 28,655 died. In multivariable multi-state models, compared with low CR, high CR was associated with lower risk of depression (hazard ratio 0.53 [95% confidence interval 0.51–0.56]) and lower risk of post-depression dementia (0.55 [0.34–0.88]) or death (0.69 [0.55–0.88]) in middle-aged adults (aged

Unlike animals, plants exhibit more complexity of sexual morphs. The genetic mechanism underlying plant sex is a hot research topic in plant biology. In recent decades, advanced theories have been put forth on plant sex determination, but experimental proof is scarce. In recent years, vast achievements have been made to reveal the genetic mechanisms underlying sex separation of plants at the molecular level. Although the sex determination mechanisms have been clarified only in a limited number of plant species thus far, the discoveries offer us an opportunity to understand the genetic mechanisms triggering the separation of plant sexes. This paper reviewed the different aspects of the advanced studies on plant sex evolution and the molecular mechanisms underlying plant sex separation.

Abstract Plant roots significantly influence soil microbial diversity, and soil microorganisms play significant roles in both natural and agricultural ecosystems. Although the genetically modified (GM) crops with enhanced insect and herbicide resistance are thought to have unmatched yield and stress resistance advantages, thorough and in‐depth case studies still need to be carried out in a real‐world setting due to the potential effects of GM plants on soil microbial communities. In this study, three treatments were used: a recipient soybean variety Jack, a triple transgenic soybean line JD321, and the glyphosate‐treated JD321 (JD321G). Three sampling stages (flowering, seed filling and maturing), as well as three host niches of soybean rhizosphere [intact roots (RT), rhizospheric soil (RS) and surrounding soil (SS)] were established. In comparison to Jack, the rhizospheric soil of JD321G had higher urease activity and lower nitrite reductase at the flowering stage. Different treatments and different sampling stages existed no significant effects on the compositions of microbial communities at different taxonomic levels. However, at the genus level, the relative abundance of three plant growth‐promoting fungal genera (i.e. Mortierella, Chaetomium and Pseudombrophila) increased while endophytic bacteria Chryseobacterium and pathogenic bacteria Streptomyces decreased from the inside to the outside of the roots (i.e. RT → RS → SS). Moreover, two bacterial genera, Bradyrhizobium and Ensifer were more abundant in RT than in RS and SS, as well as three species, Agrobacterium radiobacter, Ensifer fredii and Ensifer meliloti, which are closely related to nitrogen‐fixation. Furthermore, five clusters of orthologous groups (COGs) associated to nitrogen‐fixation genes were higher in RT than in RS, whereas only one COG annotated as dinitrogenase iron‐molybdenum cofactor biosynthesis protein was lower. Overall, the results imply that the rhizosphere host niches throughout the soil–plant continuum largely control the composition and function of the root‐associated microbiome of triple transgenic soybean.

Introduction: Flat dosing regimen has recently been approved for programmed death receptor-1 (PD-1) inhibitors including toripalimab, nivolumab and pembrolizumab. The objective of this study is to provide pharmacological evidence for a flat dosing regimen of toripalimab by assessing the efficacy and safety profile of a 240 mg Q3W flat dose relative to the currently approved 3 mg/kg Q2W.Methods: A population pharmacokinetic (PopPK) model was established based on 1,014 evaluable patients in 13 clinical studies. The exposure-objective response rate (ORR, n = 234) and exposure-safety (n = 152) analyses were performed by logistic regression. Three safety endpoints including grade ≥ 3 adverse events (AEs), treatment-related grade ≥ 3 AEs, and AEs leading to study drug discontinuation were evaluated. Progression-free survival (PFS, n = 234) was evaluated using a Cox proportional hazard model with the Kaplan-Meier survival curve.Results: The PK profiles of toripalimab are best described by a two-compartment model with time-varying clearance characterized by a sigmoidal maximum effect (Emax) function. Simulations for the first dose and steady-state exposures for the 240 mg Q3W dosing regimen were comparable to those for the 3 mg/kg Q2W dosing regimen with 95% exposure coverage ranging from 88% to 96%. The exposure-safety analysis showed that the probability of an adverse event occurring did not increase with increases in toripalimab exposure. A flat exposure-response relationship for ORR was identified. The Kaplan–Meier survival curve showed that exposure was a predictor for PFS; however, no difference in treatment benefit was demonstrated across exposure quantiles using a Cox proportional hazard model.Discussion: This study revealed that toripalimab exposure of 240 mg Q3W dosing regimen was comparable to 3 mg/kg Q2W dosing regimen. The safety and efficacy E-R results of 240 mg Q3W is flat. Hence, the 240 mg Q3W dosing regimen is determined to be a preferred therapeutic dosage for toripalimab due to the convenience of flat dose.

Root-associated fungal microbiota, which inhabit the rhizosphere, rhizoplane and endosphere, have a profound impact on plant growth and development. Sorghum bicolor (L.) Moench, also called broomcorn or sweet sorghum, is a multipurpose crop. The comparison between annual and perennial sweet sorghum cultivars in terms of plant growth, as well as their interactions with belowground fungal microbiota, is still poorly understood, although there has been growing interest in the mutualism between annual sweet sorghum and soil bacteria or bacterial endophytes. In this study, the perennial sweet sorghum cultivar N778 (N778 simply) and its control lines TP213 and TP60 were designed to grow under natural field conditions. Bulk soil, rhizosphere soil and sorghum roots were collected at the blooming and maturity stages, and then the fungal microbiota of those samples were characterized by high-throughput sequencing of the fungal ITS1 amplicon. Our results revealed that the alpha diversity of the fungal microbiota in rhizosphere soil and root samples was significantly different between N778 and the two control lines TP213 and TP60 at the blooming or maturity stage. Moreover, beta diversity in rhizosphere soil of N778 was distinct from those of TP213 and TP60, while beta diversity in root samples of N778 was distinct from those of TP213 but not TP60 by PCoA based on Bray–Curtis and WUF distance metrics. Furthermore, linear discriminant analysis (LDA) and multiple group comparisons revealed that OTU4372, a completely unclassified taxon but with symbiotroph mode, was enriched in sorghum roots, especially in N778 aerial roots at the blooming stage. Our results indicate that Cladosporium and Alternaria, two fungal genera in the rhizosphere soil, may also be dominant indicators of sorghum yield and protein content in addition to Fusarium at the maturity stage and imply that the perennial sweet sorghum N778 can primarily recruit dominant psychrotolerant bacterial taxa but not dominant cold-tolerant fungal taxa into its rhizosphere to support its survival below the freezing point.

Transgenic technology has been widely applied to crop development, with genetically modified (GM) maize being the world’s second-largest GM crop. Despite the fact that rhizosphere bacterial and fungal populations are critical regulators of plant performance, few studies have evaluated the influence of GM maize on these communities. Plant materials used in this study included the control maize line B73 and the mcry1Ab and mcry2Ab dual transgenic insect-resistant maize line 2A-7. The plants and soils samples were sampled at three growth stages (jointing, flowering, and maturing stages), and the sampling compartments from the outside to the inside of the root are surrounding soil (SS), rhizospheric soil (RS), and intact root (RT), respectively. In this study, the results of alpha diversity revealed that from the outside to the inside of the root, the community richness and diversity declined while community coverage increased. Morever, the different host niches of maize rhizosphere and maize development stages influenced beta diversity according to statistical analysis. The GM maize line 2A-7 had no significant influence on the composition of microbial communities when compared to B73. Compared to RS and SS, the host niche RT tended to deplete Chloroflexi, Gemmatimonadetes and Mortierellomycota at phylum level. Nitrogen-fixation bacteria Pseudomonas, Herbaspirillum huttiense, Rhizobium leguminosarum, and Sphingomonas azotifigens were found to be enriched in the niche RT in comparison to RS and SS, whilst Bacillus was found to be increased and Stenotrophomonas was found to be decreased at the maturing stage as compared to jointing and flowering stages. The nitrogen fixation protein FixH (clusters of orthologous groups, COG5456), was found to be abundant in RT. Furthermore, the pathogen fungus that causes maize stalk rot, Gaeumannomyces radicicola, was found to be abundant in RT, while the beneficial fungus Mortierella hyalina was found to be depleted in RT. Lastly, the abundance of G. radicicola gradually increased during the development of maize. In conclusion, the host niches throughout the soil-plant continuum rather than the Bt insect-resistant gene or Bt protein secretion were primarily responsible for the differential assembly of root-associated microbial communities in GM maize, which provides the theoretical basis for ecological agriculture.

Abstract Shikonin and its derivatives are the main components of traditional Chinese medicine, Zicao. The pharmacological potential of shikonin and its derivatives have been extensively studied. Yet, less is known about the microbial assemblages associated with shikonin producing Borage plants. We studied microbial profiles of two Borage species, Echium plantagineum (EP) and Lithospermum erythrorhizon (LE), to identify the dynamics of microbial colonization pattern within three rhizo-compatments and two distinct soil types. Results of α and β-diversity via PacBio sequencing revealed significantly higher microbial richness and diversity in the natural soil along with a decreasing microbial gradient across rhizosphere to endosphere. Our results displayed genotype and soil type–dependent fine-tuning of microbial profiles. The host plant was found to exert effects on the physical and chemical properties of soil, resulting in reproducibly different micro-biota. Analysis of differentially abundant microbial OTUs displayed Planctomycetes and Bacteroidetes to be specifically enriched in EP and LE rhizosphere while endosphere was mostly prevailed by Cyanobacteria. Network analysis to unfold co-existing microbial species displayed different types of positive and negative interactions within different communities. The data provided here will help to identify microbes associated with different rhizo-compartments of potential host plants. In the future, this might be helpful for manipulating the keystone microbes for ecosystem functioning.

Abstract Background A key component of the 2009 medical reform in China was the change to family doctor (FD) policy practice. However, this led to an increased workload for primary health-care workers (PHCWs) at community health service centres. Their increasing workload may play a significant role in affecting PHCWs’ health. Methods A questionnaire survey was conducted in Hongkou district of Shanghai amongst PHCWs including family doctors (FDs), family nurses (FNs), public health doctors (PHDs), and other PHCWs in early 2019. Ordered logistic regression models (Models 1 to 3) were performed to explore the differing health status amongst PHCWs, and their respective influential factors were also tested (Models 4 to 7). Results Five hundred sixty-two valid questionnaires were collected with a response rate of 96.4%. Other PHCWs’ (OR = 2.03; 95% CI: 1.163–3.560) and FNs’ (OR = 1.98; 95% CI: 1.136–3.452) self-rated health (SRH) were significantly better than that of FDs. In terms of FNs, the OR of SRH for those who strongly perceived the extra workload brought by FD-contracted services was only 12.0% (95% CI: 0.018–0.815) of that of the no-pressure group. Similarly, FNs with stronger work pressure had worse SRH, i.e., compared with “no” pressure, the SRH ORs for “neutral,” “strong,” and “very strong” evaluations of work pressure were 0.002 (95% CI: 0.000–0.055), 0.001 (95% CI: 0.000–0.033), and 0.000 (95% CI: 0.000–0.006), respectively. Information technology (IT) systems and performance incentives were suggested to improve SRH for FNs, while the former was found to be negatively correlated with other PHCWs. After one unit increase in the PHDs’ team/department support, their OR was 10.7 times (95% CI: 1.700–67.352) higher. In addition, policy support had a negative effect on SRH for PHDs. The OR of “good” assessments of cultural environments was 25.98 times (95% CI: 1.391–485.186) higher than that of “very poor” for Other PHCWs. Conclusions The influences of FD policy practice on FNs’ SRH were the most significant amongst PHCWs, rather than FDs’ as expected. The significant factors of SRH were varied over different occupational categories, that is team/department support and policy support (though negative) for PHDs, IT system and incentive for FNs, facility and equipment for FDs, and culture environment for other PHCWs respectively.

The BAHD acyltransferase family is a unique class of plant proteins that acylates plant metabolites and participates in plant secondary metabolic processes. However, the BAHD members in Lithospermum erythrorhizon remain unknown and uncharacterized. Although the heterologously expressed L. erythrorhizon BAHD family member LeSAT1 in Escherichia coli has been shown to catalyze the conversion of shikonin to acetylshikonin in vitro, its in vivo role remains unknown. In this study, the characterization, evolution, expression patterns, and gene function of LeBAHDs in L. erythrorhizon were explored by bioinformatics and transgenic analysis. We totally identified 73 LeBAHDs in the reference genome of L. erythrorhizon. All LeBAHDs were phylogenetically classified into five clades likely to perform different functions, and were mainly expanded by dispersed and WGD/segmental duplication. The in vivo functional investigation of the key member LeBAHD1/LeSAT1 revealed that overexpression of LeBAHD1 in hairy roots significantly increased the content of acetylshikonin as well as the conversion rate of shikonin to acetylshikonin, whereas the CRISPR/Cas9-based knockout of LeBAHD1 in hairy roots displayed the opposite trend. Our results not only confirm the in vivo function of LeBAHD1/LeSAT1 in the biosynthesis of acetylshikonin, but also provide new insights for the biosynthetic pathway of shikonin and its derivatives.

The phytohormone auxin plays a pivotal role in the regulation of plant growth and development, including vascular differentiation and tree growth. The auxin/indole-3-acetic acid (Aux/IAA) and auxin response transcription factor (ARF) genes are key components of plant auxin signaling. To gain more insight into the regulation and functional features of Aux/IAA and ARF genes during these processes, we identified 38 AUX/IAA and 34 ARF genes in the genome of Salix suchowensis and characterized their gene structures, conserved domains, and encoded amino acid compositions. Phylogenetic analysis of some typical land plants showed that the Aux/IAA and ARF genes of Salicaceae originated from a common ancestor and were significantly amplified by the ancestral eudicot hexaploidization event and the “salicoid” duplication that occurred before the divergence of poplar and willow. By analyzing dynamic transcriptome profiling data, some Aux/IAA and ARF genes were found to be involved in the regulation of plant growth, especially in the initial plant growth process. Additionally, we found that the expression of several miR160/miR167-ARFs was in agreement with canonical miRNA–ARF interactions, suggesting that miRNAs were possibly involved in the regulation of the auxin signaling pathway and the plant growth process. In summary, this study comprehensively analyzed the sequence features, origin, and expansion of Aux/IAA and ARF genes, and the results provide useful information for further studies on the functional involvement of auxin signaling genes in the plant growth process.

Pipe routing and clamp layout for aeroengine are NP-hard computational problems and complex engineering design processes. Besides space constraints and engineering rules, there are assembly constraints between pipes and clamps, which usually lead to repeatedly modifications between pipe routing and clamp layout designs. In order to solve the problems of assembly constraints and design coupling between them, an integrated optimization method for pipe routing and clamp layout is proposed. To this end, the MOALO (multiobjective ant lion optimizer) algorithm is modified by introducing the levy flight strategy to improve the global search performance and convergence speed, and it is further used as a basic computation tool. The integrated optimization method takes pipe and clamp as a whole system and then solves the Pareto solution set of pipe-clamp layouts by using improved MOALO, where the pipe path, clamp position, and rotation angle are selected as decision variables and are further optimized. Inspired by engineering experience, a clamp-based pipe path mechanism considering regular nodes is established to deal with assembly constraint problem. The proposed method comprehensively considers engineering rules of pipe routing and clamp layout and realizes the overall layout optimization of pipe-clamp system while guaranteeing the assembly constraints between pipes and clamps. Finally, some numerical computations and routing examples are conducted to demonstrate the feasibility and effectiveness of the proposed method.

Abstract Background This study aimed to investigate the expression of P90 Ribosomal Protein S6 kinase 4 (RSK4) in colorectal cancer cells and its biological function. Methods We selected early SW480 and HCT116 colorectal cancer cell lines, using Lipofectamine™ 2000 transfection reagent carrying RSK4 gene transfected into cells to establish the colorectal cancer cell lines with high expression of RSK4. RT-PCR and western blot (WB) analysis confirmed RSK4 expression in SW480 and HCT116 cancer cell lines. We used methylthiazoltetrazolium (MTT) assay and flow cytometry to detect the proliferation of colorectal cancer cells. After transfection of RSK4, the effect of RSK4 on the RNA levels associated with epithelial–mesenchymal transition (EMT) of colorectal cancer cells was analyzed by real-time fluorescence quantitative PCR and the expression of EMT-related protein was detected by WB analysis. Results After transfection of RSK4 overexpression, the MTT assay detected that RSK4 could significantly inhibit the growth of colorectal cancer cells in vitro; flow cytometry detected that S-phase cells decreased significantly, and G0/1 cells increased significantly (P

Modern agriculture has gained significant economic benefits worldwide with the use of genetically modified (GM) technologies. While GM crops provide convenience to humans, their biosafety has attracted increasing concern. In this study, the Illumina MiSeq was used to perform a high-throughput sequencing of the V3-V4 hypervariable regions of 16S rRNA gene (16S rDNA) amplicons to compare the rhizosphere bacterial communities of the EPSPS/GAT dual transgenic glyphosate-tolerant soybean line Z106, its recipient variety ZH10, and Z106 with glyphosate application (Z106G) during flowering, seed filling, and maturing stages under field settings. At each of the three stages, the alpha and beta diversity of rhizosphere bacterial communities revealed no significant differences between ZH10, Z106, and Z106G. However, some bacterial taxa demonstrated a greater proportional contribution, particularly the nitrogen-fixing rhizobium Ensifer fredii, in the rhizospheric soil of Z106 at the seed filling and maturing stages, when compared to ZH10 and Z106G. The present study therefore suggests that the EPSPS/GAT dual transgenic line Z106 and exogenous glyphosate application have a minimal effect on the composition of the soybean rhizosphere bacterial community but have no impact on the structure of the rhizosphere microbial community during a single planting season.

Although arsenite [As(III)] is non-essential and toxic for plants, it is effectively absorbed through various transporters into the roots. Here we identified a calcium-dependent protein kinase (CPK31) response for As(III) tolerance in Arabidopsis. We identified CPK31 as an interacting protein of a nodulin 26-like intrinsic protein (NIP1;1), an aquaporin involved in As(III) uptake. Similarly to the nip1;1 mutants, the loss-of-function mutants of CPK31 improved the tolerance against As(III) but not As(V), and accumulated less As(III) in roots than that of the wild-type plants. The promoter-β-glucuronidase and quantitative Real-Time PCR analysis revealed that CPK31 displayed overlapping expression profiles with NIP1;1 in the roots, suggesting that they might function together in roots. Indeed, the cpk31 nip1;1 double mutants exhibited stronger As(III) tolerance than cpk31 mutants, but similar to nip1;1 mutants, supporting the idea that CPK31 might serve as an upstream regulator of NIP1;1. Furthermore, transient CPK31 overexpression induced by dexamethasone caused the decrease in As(III) tolerance of transgenic Arabidopsis lines. These findings reveal that CPK31 is a key factor in As(III) response in plants.

It has been shown that Faecalibacterium prausnitzii (F. prausnitzii), one of the dominant intestinal bacterial flora, may protect colonic mucosa against the development of inflammation and subsequent inflammatory bowel disease (IBD), with the underlying mechanisms being unclear.The impacts of F. prausnitzii and its metabolites on IL-23/Th17/IL-17 pathway markers were determined in human monocytes and a rat model of colitis induced by 2,4,6-trinitrobenzene sulfonic acid. F. prausnitzii and its culture medium (containing complete metabolites) were used to treat the rats in vivo, as well as rat splenocytes and human monocytes in vitro. Inflammatory cytokines were measured in colon tissue, plasma and cell culture medium.The culture supernatant of F. prausnitzii increased plasma anti-Th17 cytokines (IL-10 and IL-12)and suppressed IL-17 levels in both plasma and colonic mucosa, with ameliorated colonic colitis lesions. This inhibition of IL-17 release has also been observed in both rat splenocytes and human venous monocytes in vitro. The culture supernatant of F. prausnitzii also suppressed Th17 cell differentiation induced by cytokines (TGF-ß and IL-6) and bone marrow-derived dendritic cells (BMDCs) in vitro. The metabolites of F. prausnitzii in the culture supernatant exert a stronger anti-inflammatory effect than the bacterium itself. F. prausnitzii protected the colon mucosa against the development of IBD by its metabolites, suggesting a promising potential for the use of F. prausnitzii and its metabolic products in the treatment of IBD.

Radiotherapy is still one of the effective means for treatment of malignant tumors up to now. Particularly, it is an indispensable effective measure for treatment of some lymphoma patients. In routine work, radiation pneumonitis (RP) is the most significant complication of acute treatment-related toxicities in lung cancer; however, serious radioactive pneumonia is rare for the radiotherapy of neck lymphoma because the volume of the lungs affected by radiation dose was very small. We report a lymphoma case, where the patient had undergone radiotherapy for the bilateral neck and bilateral supraclavicular/infraclavicular area. Following completion of radiotherapy, the patient developed severe radiation pneumonitis.

The title compound, C19H19NO10, was obtained from the reaction of α-d-1-bromo-2,3,4-tri-O-acetylxylose with N-hydroxyphthalimide in the presence of potassium carbonate. The asymmetric unit contains two independent molecules, in which the O—CH—O—N torsion angles are 73.0 (4) and 65.0 (4)°. The hexapyranosyl rings adopt chair conformations and the substituent groups are in equatorial positions. In the crystal, molecules are linked by nonclassical C—H...O hydrogen bonds.

In the crystal structure of the title compound, C21H25NO11, the hexopyranosyl ring adopts a chair conformation and the five substituents are in equatorial positions. An intramolecular hydrogen bond between the amino group and a neighbouring carbonyl group is found. Two carbonyl groups are disordered and were refined using a split model.

The highly pathogenic avian influenza H5N1 virus can infect a variety of animals and continually poses a threat to animal and human health. While many genotypes of H5N1 virus can be found in chicken, few are associated with the infection of mammals. Characterization of the genotypes of viral strains in animal populations is important to understand the distribution of different viral strains in various hosts. This also facilitates the surveillance and detection of possible emergence of highly pathogenic strains of specific genotypes from unknown hosts or hosts that have not been previously reported to carry these genotypes.Two H5N1 isolates were obtained from lung samples of two raccoon dogs that had died from respiratory disease in China. Pathogenicity experiments showed that the isolates were highly pathogenic to chicken. To characterize the genotypes of these viruses, their genomic sequences were determined and analyzed. The genetic contents of these isolates are virtually identical and they may come from the same progenitor virus. Phylogenetic analysis indicated that the isolates were genetically closely related to genotype V H5N1 virus, which was first isolated in China in 2003, and were distinct from the dominant virus genotypes (e.g. genotype Z) of recent years. The isolates also contain a multibasic amino acid motif at their HA cleavage sites and have an E residue at position 627 of the PB2 protein similar to the previously-identified avian viruses.This is the first report that genotype V H5N1 virus is found to be associated with a mammalian host. Our results strongly suggest that genotype V H5N1 virus has the ability to cross species barriers to infect mammalian animals. These findings further highlight the risk that avian influenza H5N1 virus poses to mammals and humans, which may be infected by specific genotypes that are not known to infect these hosts.

In the title compound, C19H20Cl2O10, the hexopyranosyl ring adopts a chair conformation. The four substituents are in equatorial positions. The molecules arelinked via C—H...O contacts along the a axis.

The aim of this study was to investigate the molecular mechanism by which miR-497-5p regulates neuronal injury after ischemic stroke through the BDNF/TrkB/Akt signaling pathway. PC12 cells were used to construct a stroke injury model by oxygen-glucose deprivation/reoxygenation (OGD/R). The expression level of miR-497-5p was measured by RT-qPCR. CCK-8 kit was used to detect cell viability. Cell apoptosis and reactive oxygen species (ROS) were detected by flow cytometry. MDA and SOD detection kits were used to detect MDA content and SOD activity. A double luciferase reporter system was used to verify the targeting relationship between miR-497-5p and BDNF. The expression of BDNF, TrkB, p-TrkB, Akt and p-Akt was detected by Western blot. We have found that miR-497-5p expression was inhibited after treatment with OGD/R. Simultaneously, cell apoptosis, MDA content and ROS were upregulated, while cell viability and SOD were significantly decreased in PC12 cells. The effects of OGD/R on PC12 cells were reversed with the downregulation of miR-497-5p. A double luciferase reporter assay demonstrated that miR-497-5p negatively targets BDNF. BDNF inhibited cell apoptosis and oxidative stress injury in PC12 cells. These findings suggest that miR-497-5p aggravates neuronal injury in experimental model of ischemic stroke by inhibiting the BDNF/TrkB/PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]