Thymectomy is routinely carried out in patients with myasthenia gravis (MG) and thymomas. However, there is still a dispute as to whether MG patients with thymic hyperplasia should undergo ...thymectomy. We aimed to investigate the pathological findings in the thymus in patients with co-existing MG and thymic hyperplasia or thymomas treated with thymectomy, as well as effects of immunosuppression. Thirty-three patients with MG were selected and grouped accordingly: patients with no thymic abnormalities, patients with thymic hyperplasia, and patients with thymomas. All patients were treated with methylprednisolone alongside immunosuppression. A separate cohort of 24 MG patients with thymic hyperplasia or thymomas and treated with thymectomy were selected. As controls, 5 patients with thymomas or thymic carcinoma without MG were selected. Expression of CD5, extracellular regulated protein kinases1/2 mitogen activated protein kinase (ERK1/2MAPKs) and CD95 ligand (FasL) in the thymus was examined. Methylprednisolone and immunosuppressive therapy are highly effective in MG patients with normal thymus tissue and MG patients with thymic hyperplasia compared to MG patients with thymomas alone. CD5 expression was highest in MG patients with thymic hyperplasia, correlating with expression of ERK1/2MAPKs. FasL expression was similar across all groups. Thymomas may be distinguished from thymic hyperplasia by expression of CD5 and ERK1/2MAPKs. Thymectomy is the preferred treatment for MG patients with thymomas but may not be necessary in MG patients with thymic hyperplasia who are treated with immunosuppressive therapy.
It was previously reported that cytokines and neurotoxins released from activated inflammatory cells induced the loss of projecting dopaminergic neurons in the substantia nigra, which triggered the ...pathogenesis of PD. The present study investigated the effect of treatment with tetramethylpyrazine (TMP) on the central cytokine synthesis, striatal dopamine content and glutamatergic transmission, and behavioral performance in the rotarod task in mice injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Treatment with TMP significantly improved the behavioral performance in the rotarod task in mice injected with MPTP. It also decreased the upregulation of cytokines (tumor necrosis factor-α and interleukin-1β) in the substantia nigra and striatum in these modeled mice. Furthermore, treatment with TMP significantly improved the dopamine deficits and attenuated the upregulation of striatal basal glutamatergic strength in the striatum of mice injected with MPTP. These results indicated that TMP might serve as a novel approach for the treatment of patients with PD.
Display omitted
•The ore-associated Kaladawan granite yielded zircon U–Pb age of 476.1±3.3Ma.•The granites are highly fractionated I-type.•The ore field was formed in an active continental ...margin.•The deposits in Kaladawan are skarn-type.
The Kaladawan Fe–Mo ore field (Altyn, Xinjiang) in Northwest (NW) China contains six deposits, with a total reserve of 60Mt Fe and 10Kt Mo metal. The orebodies are hosted in lower Paleozoic andesite, dacite, phyllite and marble with well-developed skarn alteration. The Kaladawan granites are newly U–Pb dated to be Early Ordovician (476.1±3.3Ma), largely coeval with the Fe–Mo mineralization (molybdenite Re–Os: 480.3±3.2Ma). The granites contain high SiO2, K2O and Al2O3, low TiO2, MgO and CaO, with high K2O/Na2O ratios (1.26–1.58) and A/CNK values (1.00–1.08), showing peraluminous high-K calc-alkaline affinity. The rocks are characterized by large ion lithophile element (LILE) and light rare earth element (LREE) enrichments and depletions of Sr, Ba, Nb, Ta, Ti and P, and with negative Eu anomalies. The rocks have initial 87Sr/86Sr ratios of 0.7066 to 0.7112 and εNd(t) values of −1.4 to −1.1, with TDM2(Nd) ages of 1.32–1.30Ga. Zircon εHf(t) values range from 2.9 to 6.4, with TDM2(Hf) ages of 1.26–1.04Ga. The new geochemical and isotopic data suggest that the Kaladawan granites are highly fractionated I-type, and likely formed by fractional crystallization of a magma that was derived from partial melting of a mixture of crustal and mantle materials. Deposits in the Kaladawan Fe–Mo field are skarn-type and may have occurred in an active continental margin, via the contact metamorphism and metasomatic reaction between granite-derived fluids and the wall rocks.
New Omicron subvariants continue to emerge throughout the world. In particular, the XBB subvariant, which is a recombinant virus between BA.2.10.1.1 and BA.2.75.3.1.1.1, as well as the BA.2.3.20 and ...BR.2 subvariants that contain mutations distinct from BA.2 and BA.2.75, are currently increasing in proportion of variants sequenced. Here we show that antibodies induced by 3-dose mRNA booster vaccination as well as BA.1- and BA.4/5-wave infection effectively neutralize BA.2, BR.2, and BA.2.3.20 but have significantly reduced efficiency against XBB. In addition, the BA.2.3.20 subvariant exhibits enhanced infectivity in the lung-derived CaLu-3 cells and in 293T-ACE2 cells. Overall, our results demonstrate that the XBB subvariant is highly neutralization resistant, which highlights the need for continued monitoring of the immune escape and tissue tropism of emerging Omicron subvariants.
Display omitted
•3-dose mRNA vaccination-induced antibodies barely neutralize XBB•BA.1 and BA.4/5 infection-induced antibodies weakly neutralize XBB•BR.2 and BA.2.3.20 have similar neutralization to the parental BA.2•BA.2.3.20 exhibits enhanced infectivity in the lung-derived CaLu-3 cells
Faraone et al. investigate the infectivity and neutralization of Omicron subvariants BR.2, BA.2.3.20, and XBB. They show remarkable neutralization escape by XBB, but not BR.2 and BA.2.3.20, for 3-dose mRNA vaccination or natural BA.1 or BA.4/5 infection. BA.2.3.20 also exhibits enhanced infectivity in the lung-derived CaLu-3 cells.
AIM: To identify the genetic defects of a Chinese patient with sporadic retinitis pigmentosa(RP).METHODS: Ophthalmologic examinations were performed on the sporadic RP patient, 144 genes associated ...with retinal diseases were scanned with capture next generation sequencing(CNGS) approach.Two heterozygous mutations in PDE6B were confirmed in the pedigree by Sanger sequencing subsequently. The carrier frequency of PDE6B mutations of reported PDE6B mutations based on the available two public exome databases(1000 Genomes Project and ESP6500 Genomes Project) and one in-house exome database was investigated.RESULTS: We identified compound heterozygosity of two novel nonsense mutations c.1133G>A(p.W378X) and c.2395C>T(p.R799X) in PDE6B, one reported causative gene for RP. Neither of the two mutations in our study was presented in three exome databases. Two mutations(p.R74 C and p.T604I) in PDE6B have relatively high frequencies in the ESP6500 and in-house databases,respectively, while no common dominant mutation in each of the database or across all databases.CONCLUSION: We demonstrates that compound heterozygosity of two novel nonsense mutations in PDE6B could lead to RP. These results collectively point to enormous potential of next-generation sequencing in determining the genetic etiology of RP and how various mutations in PDE6B contribute to the genetic heterogeneity of RP.
The Kaladawan Fe–Mo ore field in Altyn (Xinjiang Province, NW China) contains six Fe (–Mo) deposits, with total proven reserves of 60Mt Fe and 10,000t Mo. Tabular, lensoidal and stratiform orebodies ...occur in the Cambrian foliated marble, phyllite, carbonaceous slate, chlorite–sericite schist and quartz–sericite schist along the exocontact zone of the Kaladawan granite. Skarns are extensively developed and dominated by garnet, pyroxene, epidote, tremolite and actinolite, with minor chlorite, zoisite, quartz and calcite. Ore minerals are mainly magnetite and molybdenite. Five alteration and mineralization stages (I–V) were identified: the prograde (I) and retrograde (II) skarns are characterized by assemblages of garnet–pyroxene and epidote–tremolite–actinolite, respectively, intruded and replaced by mineral assemblages of magnetite–epidote–zoisite (III), quartz–sulfides (IV) and calcite–chlorite (V) in younging order. The Kaladawan garnet contains more andradite (61.2–94.4mol%) than grossularite (37.5–5.0mol%). Pyroxene is Mg-rich and Fe-poor, with an endmember range of 55.4–94.7mol% diopside and 42.5–4.7mol% hedenbergite. Amphibole comprises mainly tremolite and actinolite. The Kaladawan skarn mineral contents resemble typical skarn Fe and Mo deposits. In-situ LA-ICP-MS magnetite trace element analysis had identified unusually high Mg, Mo and Cr concentrations. The high Mo and the absence of molybdenite inclusions in magnetite suggest that the hydrothermal fluids may have been Mo-rich. The magnetite also contains similar (Ti+V) and (Al+Mn) values with typical skarn Fe deposits. Therefore, the Kaladawan Fe–Mo mineralization is best attributed to be skarn-type, and related to the Kaladawan granite intrusion.
Display omitted
•A new Fe–Mo field was discovered at Kaladawan in the Altyn Mountains.•The skarn minerals have compositions similar to those of typical iron deposits.•In-situ Trace elemental features of magnetite indicate a skarn origin.•The Mo mineralization and Mo-rich magnetite formed by Mo-rich hydrothermal fluids.•The Kaladawan Fe–Mo ore field is a skarn system.
To explore the association of ALOX5AP single nucleotide polymorphisms (SNPs) and haplotype with the occurrence of cerebral infarction in the Han population of northern China.
Blood samples were ...collected from 236 patients of Han ancestry with a history of cerebral infarction and 219 healthy subjects of Han ancestry with no history of cerebral infarction or cardiovascular disease. Applied Biosystems(®) TaqMan(®) SNP Genotyping Assays for SNP genotyping were used to determine the genotypes of 7 ALOX5AP SNP alleles (rs4073259, rs4769874, rs9315050, rs9551963, rs10507391, rs9579646, and rs4147064).
One SNP allele (A) of rs4073259 was significantly associated with development of cerebral infarction (P = 0.049). In comparison to control groups, haplotype rs9315050&rs9551963 AAAC OR (95% CI) = 1.53 (1.02-2.29), and genotypes rs4147064 CT OR (95% CI) = 1.872 (1.082-3.241), and rs9551963 AC OR (95% CI) = 2.015 (1.165-3.484) increased the risk of cerebral infarction in patients with hypertension. Genotype rs9579646 GG OR (95% CI) = 2.926 (1.18-7.251) increased the risk of, while rs4073259 GG OR (95% CI) = 0.381 (0.157-0.922) decreased the risk of cerebral infarction in patients with diabetes.
These results suggest the ALOX5AP SNP A allele in rs4073259 and genotype rs9579646 GG, rs9551963 AC, and haplotype rs9315050 & rs9551963 AAAC were associated with an increased risk of ischemic stroke in the Han population, while rs4073259 GG was associated with a decreased risk.
Phytochemical study of Orobanche cernua Loefling afforded 17 compounds, including eleven phenylpropanoid glycosides (1–11), two flavonoids (12, 13), one lignan (14), and three phenolic acids (15–17) ...were isolated from the fresh whole plant of O. cernua. Their structures were identified by spectroscopic analyses and by comparison of their spectral data with those reported in the literature. This is the first report of isolation of compounds (6, 8, 9, 11, 14–16) from O. cernua and compounds (14, 15) from the family Orobanchaceae, respectively. Compound 14 was obtained from natural source for the first time, the chemotaxonomic significance of these compounds was summarized.
•Seven compounds were isolated from Orobanche cernua Loefling for the first time.•Dimethyl 6,9,10-Trihydroxybenzoklxanthene-1,2-dicarboxylate is identified as a new natural product.•This is a first report of the presence of trans-ferulic acid and a lignan with benzoxanthene skeleton in Orobanchaceae.•Potential chemotaxonomic markers were summarized.
A novel phenylethanoid glycoside, 3′-O-methyl isocrenatoside (1), along with two known compounds, methyl caffeate (2) and protocatechuic aldehyde (3), were isolated from the fresh whole plant of ...Orobanche cernua Loefling. All the isolated compounds (1 – 3) were elucidated on the basis of spectroscopic analysis including IR, MS and NMR data. The cytotoxic activities of these compounds were evaluated. Results showed that 3′-O-methyl isocrenatoside (1) and methyl caffeate (2) exhibited significant cytotoxicity, with IC ₅₀ values of 71.89, 36.97 μg/mL and 32.32, 34.58 μg/mL against the B16F10 murine melanoma and Lewis lung carcinoma cell lines, respectively.
Orobanche cernua is one of the species of Orobanche in Orobanchaceae family, which has been used in folk medicines for boost immunity and relieve swelling. The present study aimed to analyse the ...chemical constituents of the essential oils (EO) from O. cernua by GC/MS and evaluate the cytotoxic activity in vitro. Twenty-eight compounds, representing 83.41 % of the total EO were identified and the major volatile components were diethylhexyl adipate (35.34 %), followed by 2-methylheptane (12.65 %), α-cadinol (7.25 %), diethylphthalate (5.17 %), dibutyl phthalate (4.07 %), 3-methylheptane (3.51 %) and 1-tetradecanol (3.39 %). The EO cytotoxicity on the tumor cell lines (SH-SY5Y and BV-2) was determined by MTT assay and cell imaging, the results indicated that the potent cytotoxic effects with the IC
50
values (55.89 μg/mL) in SH-SY5Y cells but weak in BV-2 cells with the IC
50
(482.1 μg/mL) for 24 h, respectively. This paper is the first report of the chemical composition and cytotoxic activity of EO from O. cernua.
PDF
