Abnormal changes of bone metabolism markers with age in children with cerebral palsy

Cerebral palsy (CP) is a broad range of diseases with permanent and nonprogressive motor impairments, carrying a high cost for both the individual and the society. The characteristics of low bone mineral density and high risk of fractures suggest that bone metabolism disorders are present in CP. This study aims to investigate the association between indicators of bone metabolism and children with CP. A total of 139 children (75 children with CP and 64 healthy controls) were included in this cross-sectional study. Participants were divided into three age groups (0–2 years, 2.1–4 years, and 4.1–7 years). All children with CP were diagnosed according to clinical criteria and furtherly divided into clinical subtypes. The levels of total procollagen type I N-terminal propeptide (TPINP), N-MID osteocalcin (OC), beta-crosslaps (β-CTX), 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH) in the serum were measured with corresponding detection kits according to the manufacturer's instructions. Serum levels of TPINP and 25-OHD were lower with older age, whereas β-CTX and PTH were higher with older age. In the CP group, TPINP (age 0–2 years and 2.1–4 years) and OC (age 2.1–4 years) levels were higher, while β-CTX (age 2.1–4 years and 4.1–7 years) and PTH (age 2.1–4 years) values were lower than the control group. In addition, there were no statistically significant differences in the levels of these indicators among the CP subgroups with different clinical characteristics. Our study shows that bone turnover markers, indicators of bone metabolism, in children with CP differ significantly from healthy controls. The indicators we studied changed with age, and they did not correlate with disease severity

Unconventional secretion of unglycosylated ORF8 is critical for the cytokine storm during SARS-CoV-2 infection

Coronavirus disease 2019 is a respiratory infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence on the pathogenesis of SARS-CoV-2 is accumulating rapidly. In addition to structural proteins such as Spike and Envelope, the functional roles of non-structural and accessory proteins in regulating viral life cycle and host immune responses remain to be understood. Here, we show that open reading frame 8 (ORF8) acts as messenger for inter-cellular communication between alveolar epithelial cells and macrophages during SARS-CoV-2 infection. Mechanistically, ORF8 is a secretory protein that can be secreted by infected epithelial cells via both conventional and unconventional secretory pathways. Conventionally secreted ORF8 is glycosylated and loses the ability to recognize interleukin 17 receptor A of macrophages, possibly due to the steric hindrance imposed by N-glycosylation at Asn78. However, unconventionally secreted ORF8 does not undergo glycosylation without experiencing the ER-Golgi trafficking, thereby activating the downstream NF-κB signaling pathway and facilitating a burst of cytokine release. Furthermore, we show that ORF8 deletion in SARS-CoV-2 attenuates inflammation and yields less lung lesions in hamsters. Our data collectively highlights a role of ORF8 protein in the development of cytokine storms during SARS-CoV-2 infection

Clinical and Microbiological Characteristics of a Community-Acquired Carbapenem-Resistant Escherichia coli ST410 Isolate Harbouring blaNDM-5-Encoding IncX3-Type Plasmid From Blood

Objectives: The aim of this research was to investigate the clinical and microbiological characteristics of a case of community-acquired carbapenem-resistant Escherichia coli isolated from a patient with a bloodstream infection in China.Methods:Escherichia coli Huamei202001 was recovered from the first blood culture from a patient hospitalised in China. An antimicrobial susceptibility test was performed, and the genome was sequenced on an Illumina HiSeq X 10 platform with a 150-bp paired-end approach. The generated sequence reads were assembled using Unicycler, and the whole genome sequence data were analysed using bioinformatics tools. Moreover, the patient and her main family members obtained a faecal sample screening test for CRE, the positive strain was further isolated and the identification and antimicrobial susceptibility testing was performed.Results:Escherichia coli Huamei202001 belonged to sequence type 410. In addition, a blaNDM-5-encoding IncX3-type plasmid was responsible for the spreading of carbapenem resistance. Only the patient was detected as having a positive faecal sample screening test for CRE. Strain Fec01 was identified as E. coli, and the antibiotic susceptibility profile was the same as that of E. coli Huamei202001.Conclusions:Escherichia coli Huamei202001 is defined as community-acquired carbapenem-resistant Enterobacteriaceae. The clone ST410 that harbours the blaNDM-5-encoding IncX3-type plasmid is causing new high-risk clones globally. Thus, infection control measures should be strengthened to curb the dissemination of IncX3

Stray dogs as indicators of Toxoplasma gondii distributed in the environment: the first report across an urban-rural gradient in China

<p>Abstract</p> <p>Background</p> <p>Toxoplasmosis is an important parasitic zoonosis caused by the protozoan <it>Toxoplasma gondii </it>that is distributed world-wide and infects a variety of hosts. However, the prevalence of <it>T. gondii </it>in the environment (such as soil, water and food) is largely unknown. Due to the technical difficulty in oocyst counting directly, an alternative assay using the serologic status of <it>T. gondii </it>in free-living animals, such as stray or free-living dogs, as an indicator, can be used to evaluate environmental contamination indirectly, as they are exposed to the same risk of infection as humans and other animals.</p> <p>Results</p> <p>In the present study, 231 stray or free-living dogs across an urban-rural gradient were examined to assess the frequency of <it>T. gondii </it>in the environment. Specific antibodies to <it>T. gondii </it>were found in 93 dogs (40.3%) by enzyme-linked immunosorbent assay (ELISA), and no statistically significant differences were observed in seroprevalences of <it>T. gondii </it>between urban dogs (38.7%) and rural dogs (41%) (<it>p </it>> 0.05).</p> <p>Conclusions</p> <p>A high seroprevalence of <it>T. gondii </it>in stray or free-living dogs in the present study indicates that there would be a wide distribution and a constant infection pressure of <it>T. gondii </it>across an urban-rural gradient, and the oocysts of <it>T. gondii </it>in the environment would be an important source of infection for humans and other animals both in urban and rural areas in China.</p

Subacute Combined Degeneration, Pernicious Anemia and Gastric Neuroendocrine Tumor Occured Simultaneously Caused by Autoimmune Gastritis

Subacute combined degeneration (SCD) is a relatively rare myelopathy mainly caused by vitamin B12 (VitB12) deficiency. There are many causes contributing to VitB12 deficiency. Autoimmune gastritis might lead to severe VitB12 malabsorption and in its advanced stage pernicious anemia (PA) may occur. Besides, long-term hypergastrinemia arising from achlorhydria in autoimmune gastritis is associated with neuroendocrine tumors (NETs). Patients diagnosed with SCD coexistent with PA and NET are seldomly reported. We describe a 34-year-old woman with an initial complaint of progressive fatigue, weakness and numbness in her limbs and disturbed gait. Physical examination revealed appearance of anemia, ataxia, decrease of superficial and deep sense, and positive Babinski’s sign. Laboratory tests disclosed macrocytic anemia, elevated intrinsic factor antibody and spinal MRI showed extensive T2-weighted hyperintensity in the dorsal columns. A gastric polyp was revealed by gastroscopy and histology showed an NET in the background of severe atrophic gastritis. Symptoms of the patient were relieved by a multidisciplinary therapy. In patients with SCD, PA should be suspected and prompt further investigations to elucidate causes and direct treatment

Agonist-Dependent Potentiation of Vanilloid Receptor Transient Receptor Potential Vanilloid Type 1 Function by Stilbene Derivatives □ S

ABSTRACT Transient receptor potential vanilloid type 1 (TRPV1) is a nonselective cation channel activated by capsaicin, low pH, and noxious heat and plays a key role in nociception. Understanding mechanisms for functional modulation of TRPV1 has important implications. One characteristic of TRPV1 is that channel activity induced by either capsaicin or other activators can be sensitized or modulated by factors involving different cell signaling mechanisms. In this study, we describe a novel mechanism for the modulation of TRPV1 function: TRPV1 function is modulated by 4,4Ј-diisothiocyanatostilbene-2,2Ј-disulfonic acid (DIDS) and its analogs. We found that, in rat dorsal root ganglion neurons, although DIDS did not induce the activation of TRPV1 per se but drastically increased the TRPV1 currents induced by either capsaicin or low pH. DIDS also blocked the tachyphylaxis of the low pH-induced TRPV1 currents. 4-Acetamido-4Ј-isothiocyanatostilbene-2,2Ј-disulfonic acid (SITS), a DIDS analog, failed to enhance the capsaicin-evoked TRPV1 current but increased the low pH-evoked TRPV1 currents, with an effect comparable with that of DIDS. SITS also blocked the low pH-induced tachyphylaxis. DIDS also potentiated the currents of TRPV1 channels expressed in human embryonic kidney 293 cells, with an effect of left-shifting the concentrationresponse curve of the capsaicin-induced TRPV1 currents. This study demonstrates that DIDS and SITS, traditionally used chloride channel blockers, can modify TRPV1 channel function in an agonist-dependent manner. The results provide new input for understanding TRPV1 modulation and developing new modulators of TRPV1 function

Case report: ISL2 is involved in malignant transformation in a patient with multiple relapsed oligodendroglioma

The majority of oligodendrogliomas exhibit an intrinsic tendency to develop into malignant high-grade tumors. Angiogenesis is a major factor contributing to the malignant transformation of oligodendroglioma, and its molecular regulatory mechanism needs further study. We provide a case report of an oligodendroglioma patient with two recurrences whose disease progressed from WHO grade II to grade III. We showed that the expression of insulin gene enhancer protein (ISL2) and its angiogenic ability were positively correlated with the progression of oligodendroglioma. In Low-grade glioma (LGG) patients, including oligodendroglioma patients, overexpression of ISL2 was correlated with poor prognosis, and this correlation was not affected by gender or isocitrate dehydrogenase 1(IDH1) mutation status. ISL2 expression and ISL2-mediated angiogenic pathway activity are ideal biomarkers for the malignant transformation of oligodendroglioma. Anti-ISL2 therapy is also a potential treatment option for malignantly transformed oligodendroglioma

Association of the KLF14 rs4731702 SNP and Serum Lipid Levels in the Guangxi Mulao and Han Populations

The objective of the present study was to detect the association of the rs4731702 single nucleotide polymorphism (SNP) and serum lipid levels in the Guangxi Mulao and Han populations. A total of 727 subjects of Mulao and 740 subjects of Han Chinese were included. Serum low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) B levels were higher in Mulao than in Han ( &lt; 0.05). The T allele carriers had higher serum LDL-C and ApoAI levels in Mulao, whereas they had lower high-density lipoprotein cholesterol (HDL-C) levels and ratio of ApoAI to ApoB in Han ( &lt; 0.05) than the T allele noncarriers. Subgroup analyses showed that the T allele carriers had higher HDL-C, LDL-C, and ApoAI levels in Mulao males and lower ApoAI levels and ratio of ApoAI to ApoB in Han males than the T allele noncarriers. The subjects with TT genotype in Han females also had higher total cholesterol, LDL-C, ApoAI, and ApoB levels than the subjects with CT or CC genotype. Serum lipid parameters were also correlated with several environmental factors in both ethnic groups. The differences in the association of KLF14 rs4731702 SNP and serum lipid levels between the two ethnic groups might partly result from different gene-environmental interactions

First-principles study of electronic structures and optical properties of Cu, Ag, and Au-doped anatase TiO2

We perform first-principles calculations to investigate the band structure, density of states, optical absorption, and the imaginary part of dielectric function of Cu, Ag, and Au-doped anatase TiO2 in 72 atoms systems. The electronic structure results show that the Cu incorporation can lead to the enhancement of d states near the uppermost of valence band, while the Ag and Au doping cause some new electronic states in band gap of TiO2. Meanwhile, it is found that the visible optical absorptions of Cu, Ag, and Au-doped TiO2, are observed by analyzing the results of optical properties,.which locate in the region of 400-1000 nm. The absorption band edges of Cu, Ag, and Au-doped TiO2 shift to the long wavelength region compared with the pure TiO2. Furthermore, according to the calculated results, we propose the optical transition mechanisms of Cu, Ag, and Au-doped TiO2, respectively. Our results show that the visible light response of TiO2 can be modulated by substitutional doping of Cu, Ag, and Au.Comment: 12 pages, 6 figures, 43 reference