Elastic properties of transition metal dioxides: XO2_{2}(X=Ru, Rh, Os, Ir)

The elastic properties of rutile transition metal dioxides XO$_{2}$ (X=Ru, Rh, Os, and Ir) are investigated using first-principles calculations based on density functional theory. Elastic constants, bulk modulus, shear modulus, and Young's modulus as well as Possion ratio are given. OsO$_2$ and IrO$_2$ show strong incompressibility. The hardness estimated for these dioxides shows that they are not superhard solids. The obtained Debye temperatures are comparative to those of transition metal dinitrides or diborides.Comment: 14pages,2 figures,4 tables. To be published in Int. J. Mod. Phys.

Discovery of multiple lead compounds as M2 inhibitors through the focused screening of a small primary amine library.

The discovery of new anti-influenza drugs is urgent, particularly considering the recent threat of swine flu. In this study, the influenza virus M2 protein was expressed in HEK293 cells and shown to have selective ion channel activity for monovalent ions. The anti-influenza virus drug amantadine hydrochloride significantly attenuated the inward current induced by hyperpolarization of HEK293 cell membranes. Although adamantine derivatives are the only M2 drugs for influenza virus A, their use is limited in the US due to drug resistance. Here we report the discovery of multiple M2 inhibitor lead compounds that were rapidly generated through focused screening of a small primary amine library. The screen was designed using a scaffold-hopping strategy based on amantadine. This study suggests that an antiviral compound directed against a conserved motif may be more useful than amantadine in inhibiting viral replication

Sequence Characterization and Spatiotemporal Expression Patterns of PbS

Many flowering plants exhibit an important intraspecific reproductive barrier phenomenon, that is, self-incompatibility (SI), in which S-RNase genes play a significant role. To clarify the specific function of S-RNase genes in Chinese pears, the full length cDNA of PbS (26) -RNase was isolated by rapid amplification of cDNA ends (RACE) technology from Chinese white pear (Pyrus bretschneideri) cultivar “Hongpisu.” The cDNA sequence for PbS (26) -RNase was deposited in GenBank under accession number EU081888. At the amino acid level, the PbS (26) -RNase displayed the highest similarity (96.9%) with PcSa-RNase of P. communis, and only seven amino acid differences were present in the two S-RNases. Phylogenetic analysis of rosaceous S-RNases indicated that the PbS (26) -RNase clustered with maloideous S-RNases, forming a subfamily-specific not a species-specific group. The PbS (26) -RNase gene was specifically expressed in the style but not other tissues/organs. The expression level of the PbS (26) -RNase gene rapidly increased at bell balloon stage (BBS), and then it dropped after pollination. However, the abundance of the PbS (26) -RNase gene transcript in the style was greater after cross-pollination than after self-pollination. In addition, a method for rapidly detecting the PbS (26) -RNase gene was developed via allele-specific primers design. The present study could provide a scientific basis for fully clarifying the mechanism of pear SI at the molecular level

The core inflammatory factors in patients with major depressive disorder: a network analysis

IntroductionThe symptoms of major depressive disorder (MDD) vary widely. Psycho-neuro-inflammation has shown that MDD’s inflammatory factors can accelerate or slow disease progression. This network analysis study examined the complex interactions between depressed symptoms and inflammatory factors in MDD prevention and treatment.MeasuresWe gathered participants’ inflammatory factor levels, used the Hamilton Depression Scale (HAMD-17), and network analysis was used to analyzed the data. Network analysis revealed the core inflammatory (nodes) and their interactions (edges). Stability and accuracy tests assessed these centrality measures’ network robustness. Cluster analysis was used to group persons with similar dimension depressive symptoms and examine their networks.ResultsInterleukin-1β (IL-1β) is the core inflammatory factor in the overall sample, and IL-1β—interleukin-4 (IL-4) is the strongest correlation. Network precision and stability passed. Network analysis showed significant differences between Cluster 1 (with more severe anxiety/somatization and sleep disruption) and Cluster 3 (with more severe retardation and cognitive disorders), as well as between Cluster 2 (with more severe anxiety/somatization, sleep disruption and body weight) and Cluster 3. IL-1β is the core inflammatory factor in Cluster 1 and Cluster 2, while tumor necrosis factor alpha (TNF-α) in Cluster 3.ConclusionIL-1β is the central inflammatory factor in the network, and there is heterogeneity in the core inflammatory factor of MDD with specific depressive dimension symptoms as the main manifestation. In conclusion, inflammatory factors and their links should be prioritized in future theoretical models of MDD and may provide new research targets for MDD intervention and treatment

Phylogenetic and molecular characterization of coxsackievirus A24 variant isolates from a 2010 acute hemorrhagic conjunctivitis outbreak in Guangdong, China

<p>Abstract</p> <p>Background</p> <p>Acute hemorrhagic conjunctivitis is a common disease in China. As a notifiable disease, cases are registered by ophthalmologists on the AHC surveillance system. An AHC outbreak caused by CA24v was observed in Guangdong Province in 2007 by the National Disease Supervision Information Management System. Three years later, a larger outbreak occurred in Guangdong during the August-October period (2010). To characterize the outbreak and compare the genetic diversity of CA24v, which was determined to be the cause of the outbreak, the epidemiology and the molecular characterization of CA24v were analyzed in this study.</p> <p>Results</p> <p>A total of 69,635 cases were reported in the outbreak. 73.5% of index cases originated from students, children in kindergarten and factory workers, with the ≦ 9 age group at the highest risk. The male to female ratio was 1.84:1 among 0-19 years. 56 conjunctival swabs were collected to identify the causative agent from five cities with the AHC outbreak. 30 virus strains were isolated, and two of the genomes had the highest identity values (95.8%) with CA24v genomes. Four CA24v genotypes were identified by phylogenetic analysis for the VP1 and 3C regions. CA24v which caused the outbreak belonged to genotype IV. Furthermore, full nucleotide sequences for four representative isolates in 2010 and 2007 were determined and compared. 20 aa mutations, two nt insertions and one nt deletion were observed in the open reading frame, with 5'- and 3'- UTR respectively between them.</p> <p>Conclusions</p> <p>CA24v was determined to be the pathogen causing the outbreak and belongs to genotype IV. VP1 is more informative than 3C^Profor describing molecular epidemiology and we hypothesize that accumulative mutations may have promoted the outbreak.</p

CagA-positive Helicobacter pylori may promote and aggravate scrub typhus

Helicobacter pylori (H. pylori) infection may alter the host’s resistance to tsutsugamushi disease pathogens through the Th1 immune response, leading to potential synergistic pathogenic effects. A total of 117 scrub typhus cases at Beihai People’s Hospital and affiliated hospitals of Youjiang University for Nationalities and Medical Sciences were studied from January to December 2022, alongside 130 healthy individuals forming the control group. All participants underwent serum H. pylori antibody testing. The prevalence of H. pylori infection was significantly higher among scrub typhus patients (89.7%) compared to healthy individuals (54.6%) (p &lt; 0.05). Moreover, type I H. pylori infection was notably more prevalent in scrub typhus cases (67.5%) compared to healthy individuals (30%) (p &lt; 0.05). Multifactorial analysis demonstrated type I H. pylori infection as an independent risk factor for scrub typhus (adjusted odds ratio: 2.407, 95% confidence interval: 1.249–4.64, p = 0.009). Among scrub typhus patients with multiple organ damage, the prevalence of type I H. pylori infection was significantly higher (50.6%) than type II H. pylori infection (15.4%) (χ2 = 4.735, p = 0.030). These results highlight a higher incidence of H. pylori infection in scrub typhus patients compared to the healthy population. Additionally, type I H. pylori strain emerged as an independent risk factor for scrub typhus development. Moreover, individuals infected with type I H. pylori are more susceptible to multiple organ damage. These findings suggest a potential role of H. pylori carrying the CagA gene in promoting and exacerbating scrub typhus

Infection of inbred BALB/c and C57BL/6 and outbred Institute of Cancer Research mice with the emerging H7N9 avian influenza virus

A new avian-origin influenza virus A (H7N9) recently crossed the species barrier and infected humans; therefore, there is an urgent need to establish mammalian animal models for studying the pathogenic mechanism of this strain and the immunological response. In this study, we attempted to develop mouse models of H7N9 infection because mice are traditionally the most convenient models for studying influenza viruses. We showed that the novel A (H7N9) virus isolated from a patient could infect inbred BALB/c and C57BL/6 mice as well as outbred Institute of Cancer Research (ICR) mice. The amount of bodyweight lost showed differences at 7 days post infection (d.p.i.) (BALB/c mice 30%, C57BL/6 and ICR mice approximately 20%), and the lung indexes were increased both at 3 d.p.i. and at 7 d.p.i.. Immunohistochemistry demonstrated the existence of the H7N9 viruses in the lungs of the infected mice, and these findings were verified by quantitative real-time polymerase chain reaction (RT-PCR) and 50% tissue culture infectious dose (TCID50) detection at 3 d.p.i. and 7 d.p.i.. Histopathological changes occurred in the infected lungs, including pulmonary interstitial inflammatory lesions, pulmonary oedema and haemorrhages. Furthermore, because the most clinically severe cases were in elderly patients, we analysed the H7N9 infections in both young and old ICR mice. The old ICR mice showed more severe infections with more bodyweight lost and a higher lung index than the young ICR mice. Compared with the young ICR mice, the old mice showed a delayed clearance of the H7N9 virus and higher inflammation in the lungs. Thus, old ICR mice could partially mimic the more severe illness in elderly patients. </p

Targeting the BRD4/FOXO3a/CDK6 Axis Sensitizes AKT Inhibition in Luminal Breast Cancer

BRD4 assembles transcriptional machinery at gene super-enhancer regions and governs the expression of genes that are critical for cancer progression. However, it remains unclear whether BRD4-mediated gene transcription is required for tumor cells to develop drug resistance. Our data show that prolonged treatment of luminal breast cancer cells with AKT inhibitors induces FOXO3a dephosphorylation, nuclear translocation, and disrupts its association with SirT6, eventually leading to FOXO3a acetylation as well as BRD4 recognition. Acetylated FOXO3a recognizes the BD2 domain of BRD4, recruits the BRD4/RNAPII complex to the CDK6 gene promoter, and induces its transcription. Pharmacological inhibition of either BRD4/FOXO3a association or CDK6 significantly overcomes the resistance of luminal breast cancer cells to AKT inhibitors in vitro and in vivo. Our study reports the involvement of BRD4/FOXO3a/CDK6 axis in AKTi resistance and provides potential therapeutic strategies for treating resistant breast cancer

Blood transcriptome reveals immune and metabolic-related genes involved in growth of pasteurized colostrum-fed calves

The quality of colostrum is a key factor contributing to healthy calf growth, and pasteurization of colostrum can effectively reduce the counts of pathogenic microorganisms present in the colostrum. Physiological changes in calves fed with pasteurized colostrum have been well characterized, but little is known about the underlying molecular mechanisms. In this study, key genes and functional pathways through which pasteurized colostrum affects calf growth were identified through whole blood RNA sequencing. Our results showed that calves in the pasteurized group (n = 16) had higher body height and daily weight gain than those in the unpasteurized group (n = 16) in all months tested. Importantly, significant differences in body height were observed at 3 and 4 months of age (p &lt; 0.05), and in daily weight gain at 2, 3, and 6 months of age (p &lt; 0.05) between the two groups. Based on whole blood transcriptome data from 6-months old calves, 630 differentially expressed genes (DEGs), of which 235 were upregulated and 395 downregulated, were identified in the pasteurized compared to the unpasteurized colostrum groups. Most of the DEGs have functions in the immune response (e.g., CCL3, CXCL3, and IL1A) and metabolism (e.g., PTX3 and EXTL1). Protein-protein interaction analyses of DEGs revealed three key subnetworks and fifteen core genes, including UBA52 and RPS28, that have roles in protein synthesis, oxidative phosphorylation, and inflammatory responses. Twelve co-expression modules were identified through weighted gene co-expression network analysis. Among them, 17 genes in the two modules that significantly associated with pasteurization were mainly involved in the tricarboxylic acid cycle, NF-kappa B signaling, and NOD-like receptor signaling pathways. Finally, DEGs that underwent alternative splicing in calves fed pasteurized colostrum have roles in the immune response (SLCO4A1, AKR1C4, and MED13L), indicative of potential roles in immune regulation. Results from multiple analytical methods used suggest that differences in calf growth between the pasteurized and unpasteurized groups may be due to differential immune activity. Our data provide new insights into the impact of pasteurization on calf immune and metabolic-related pathways through its effects on gene expression

Characteristics of SARS-CoV-2 Omicron BA.5 variants in Shanghai after ending the zero-COVID policy in December 2022: a clinical and genomic analysis

IntroductionAn unprecedented surge of Omicron infections appeared nationwide in China in December 2022 after the adjustment of the COVID-19 response policy. Here, we report the clinical and genomic characteristics of SARS-CoV-2 infections among children in Shanghai during this outbreak.MethodsA total of 64 children with symptomatic COVID-19 were enrolled. SARS-CoV-2 whole genome sequences were obtained using next-generation sequencing (NGS) technology. Patient demographics and clinical characteristics were compared between variants. Phylogenetic tree, mutation spectrum, and the impact of unique mutations on SARS-CoV-2 proteins were analysed in silico.ResultsThe genomic monitoring revealed that the emerging BA.5.2.48 and BF.7.14 were the dominant variants. The BA.5.2.48 infections were more frequently observed to experience vomiting/diarrhea and less frequently present cough compared to the BF.7.14 infections among patients without comorbidities in the study. The high-frequency unique non-synonymous mutations were present in BA.5.2.48 (N:Q241K) and BF.7.14 (nsp2:V94L, nsp12:L247F, S:C1243F, ORF7a:H47Y) with respect to their parental lineages. Of these mutations, S:C1243F, nsp12:L247F, and ORF7a:H47Y protein were predicted to have a deleterious effect on the protein function. Besides, nsp2:V94L and nsp12:L247F were predicted to destabilize the proteins.DiscussionFurther in vitro to in vivo studies are needed to verify the role of these specific mutations in viral fitness. In addition, continuous genomic monitoring and clinical manifestation assessments of the emerging variants will still be crucial for the effective responses to the ongoing COVID-19 pandemic