Paraneoplastic neurological syndrome with positive anti-Hu and anti-Yo antibodies: A case report.

BACKGROUND: Paraneoplastic neurological syndrome (PNS) is a rare complication in patients with cancer. PNS can affect the central, peripheral, autonomic nervous system, neuromuscular junction, or muscles and cause various neurological symptoms. Anti-Yo antibody-positive neurological paraneoplasms and anti-Hu antibody-positive neurological paraneoplasms are common, but coexistence of both types has not been described in the literature. CASE SUMMARY: Here we present a rare case of paraneoplastic neuropathy occurring in both breast and lung cancers. A 55-year-old woman was admitted to our hospital with unsteadiness while walking. The patient had a history of breast cancer two years previously. Chest computed tomography revealed a 4.6 cm × 3.6 cm mass in the right lung, which was diagnosed as small-cell lung cancer (SCLC). Blood test was positive for anti-Yo antibodies, and the cerebrospinal fluid was positive for both anti-Yo and anti-Hu antibodies, and the neurological symptoms were considered to be related to the paraneoplasm. The patient was treated with a course of intravenous immunoglobulin, without noticeable improvement. After being discharged from hospital, the patient underwent regular chemotherapy for SCLC and periodic reviews. The patient's neurological symptoms continued to deteriorate at the follow-up visit in April 2021. CONCLUSION: This case suggests the possibility of two types of tumors appearing simultaneously with two paraneoplastic antibodies. The clinical appearance of two or more paraneoplastic tumors requires additional attention.

Experimental study of bubble dynamics in the neighbourhood of a vertical incomplete boundary.

The bubbles have been widely used in biomedical field, military and chemical industry. The liquid jet generated by the bubble collapse through an orifice is utilized in needle-free injections and inkjet printing. In this paper we devised synchronized triggering equipment, experimentally investigated the mechanism in the interaction of an electric-spark generated a single bubble and a vertical wall with an air-back opening. Detailed observations were recorded and described for bubble oscillation, migration, jetting, as well as the high-speed water spike penetrating through the opening. The results revealed that there was a critical value of the bubble-wall distance, below which the bubble was directed away from the incomplete boundary, while the bubble may tear from the middle for larger distance. As the distance varied, we studied the volume of the water that rushed through the opening, the velocity at the tip of the water spike, and the center of the bubble as well as the migration of the bubble boundary. This work reveals that the high-speed water spike caused by the bubble may be a potential threat to the structures, specifically for cases with a small opening size and short bubble-boundary distance.

Diabetes-Induced H3K9 Hyperacetylation Promotes Development of Alzheimer's Disease Through CDK5.

The connection between diabetes and Alzheimer's disease (AD) is not fully determined. Hyperphosphorylation of tau protein is mediated by binding and stabilization of truncated p25 with cyclin-dependent kinase-5 (CDK5) in AD. We recently showed that diabetes-associated hyperglycemia increased the CDK5 levels to promote development of AD. Here, we examined the underlying mechanisms. Hyperglycemia and glucose intolerance were induced in rats that had received a low dose of streptozotocin (STZ) and a high fat diet (HFD). Compared to the control rats that received no STZ and normal diet-fed, the STZ + HFD rats exhibited poorer performance in the behavioral test and showed hyperacetylation of H3K9 histone on CDK5 promoter, likely resulting from upregulation of a histone acetyltransferase, GCN5. Inhibition of acetylation of H3K9 histone by a specific GCN5 inhibitor, MB3, attenuated activation of CDK5, resulting in decreased tau phosphorylation in rat brain and improved performance of the rats in the behavior test. Thus, these data suggest that diabetes may promote future development of AD through hyperacetylation of H3K9 histone on CDK5 promoter.

Transcriptome Based System Biology Exploration Reveals Homogeneous Tumorigenicity of Alimentary Tract Malignancy.

Malignancies of alimentary tract include esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), colon adenocarcinoma (COAD), and rectum adenocarcinoma (READ). Despite of their similarities in cancer development and progression, there are numerous researches concentrating on single tumor but relatively little on their common mechanisms. Our study explored the transcriptomic data of digestive tract cancers from The Cancer Genome Atlas database, yielding their common differentially expressed genes including 1,700 mRNAs, 29 miRNAs, and 362 long non-coding RNAs (lncRNAs). There were 12 mRNAs, 5 miRNAs, and 16 lncRNAs in the core competitive endogenous RNAs network by RNA-RNA interactions, highlighting the prognostic nodes of SERPINE1, hsa-mir-145, and SNHG1. In addition, the weighted gene co-expression network analysis (WGCNA) illustrated 20 gene modules associated with clinical traits. By taking intersections of modules related to the same trait, we got 67 common genes shared by ESCA and READ and screened 5 hub genes, including ADCY6, CXCL3, NPBWR1, TAS2R38, and PTGDR2. In conclusion, the present study found that SERPINE1/has-mir-145/SNHG1 axis acted as promising targets and the hub genes reasoned the similarity between ESCA and READ, which revealed the homogeneous tumorigenicity of digestive tract cancers at the transcriptome level and led to further comprehension and therapeutics for digestive tract cancers.

Elevated serum macrophage migration inhibitory factor levels correlate with benign paroxysmal positional vertigo and recurrence events.

Objective: We aimed to assess the possible relations between serum levels of macrophage migration inhibitory factor (MIF), a central cytokine of the innate immunity and inflammatory response, and benign paroxysmal positional vertigo (BPPV) risk and BPPV recurrence events.Methods: In the present study, 154 patients with BPPV, and 100 age-and sex-matched control subjects were enrolled in the study. All the patients and controls underwent a complete audio-vestibular test battery including the Dix-Hallpike maneuver and supine roll test. In the BPPV group, measurements of MIF levels were repeated 1 month after the vertigo attack. The patients were also divided into the recurrence group and the nonrecurrence group in the 1-year follow-up.Results: The serum levels of MIF in patients with BPPV were higher than in those controls (13.9[interquartile range {IQR}, 8.9-18.4] ng/ml vs. 9.8[7.8-11.8]; P<0.001). As a continuous variable, MIF was associated with increased risk of BPPV (odds ratio [OR] 1.21, 95% confidence interval [CI]: 1.11-1.39; P=0.004) in multiple regression analyses. Recurrent attacks of BPPV were reported in 35 patients, and those patients had higher levels of MIF than those patients were not recurrence (18.0[IQR, 13.6-22.2] ng/ml vs. 12.6[9.3-16.8] ng/ml). In multivariate models comparing the second (Q2), third (Q3) and fourth(Q4) quartiles against the first (Q1) quartile of MIF, levels of MIF in Q4 were associated with recurrent BPPV, and the odds were increased by approximately 305% (OR = 4.05; 95%CI: 1.65-15.44; P=0.009).Conclusions: Elevated MIF is positively correlated with BPPV risk and BPPV recurrence events, requiring further efforts to clarify the exact mechanism.

Genetic analysis of roots and shoots in rice seedling by association mapping.

The vigorous shoots and roots help to improve drought resistance and post-transplanting recovery in rice seedlings (Oryza sativa L.). Hundreds of loci related to root system have been identified recently, but little research has been done on shoot traits, and the relationship between roots and shoots development is also still unclear. The objective of this study was to identify associated loci for roots and shoots in rice seedlings as well as to screen pleiotropic QTLs involved in coordinated development of roots and shoots. Using mini core collection of 273 cultivated rice accessions and 280 simple-sequence repeat markers, we investigated six traits [root length (RL), root thickness (RT), root weight (RW), shoot length (SL), shoot weight (SW) and ratio of root-to-shoot mass] in seedlings. Study was performed in hydroponic medium and genetic analysis was performed by association mapping using general linear model (GLM) with population structure (Q) and mixed linear model (MLM) involving Q and familial relatedness (K). Two subgroups indica and japonica showed significant differences in RT, RW and SW. Maximum correlation was observed between RW and SW. Using GLM 65 QTLs for root and 43 QTLs associated with shoot traits were detected. Among them, seven QTLs were present between RL and RW and five common QTLs were detected between SL and SW with high phenotypic variation effects (PVEs). Two key pleiotropic QTLs were also identified involved in collaborative development of roots and shoots in rice seedlings. Importantly, 17 and 10 QTLs were identified for root and shoot traits respectively in both studies of GLM and MLM. More common QTLs with high PVEs between root and shoot traits suggested that longitudinal growth (RL and SL) played an important role in accumulation of biomass (RW and SW). Considering the obvious phenotypic differences and fewer common QTLs between indica and japonica, we suggested that there could be different mechanisms of seedling development between both subpopulations. Key pleiotropic QTLs and QTLs identified for root and shoot traits in both studies of GLM and MLM could be preferentially used in marker-assisted breeding for strong rice seedling.

Hantavirus Gc induces long-term immune protection via LAMP-targeting DNA vaccine strategy.

Hemorrhagic fever with renal syndrome (HFRS) occurs widely throughout Eurasia. Unfortunately, there is no effective treatment, and prophylaxis remains the best option against the major pathogenic agent, hantaan virus (HTNV), which is an Old World hantavirus. However, the absence of cellular immune responses and immunological memory hampers acceptance of the current inactivated HFRS vaccine. Previous studies revealed that a lysosome-associated membrane protein 1 (LAMP1)-targeting strategy involving a DNA vaccine based on the HTNV glycoprotein Gn successfully conferred long-term immunity, and indicated that further research on Gc, another HTNV antigen, was warranted. Plasmids encoding Gc and lysosome-targeted Gc, designated pVAX-Gc and pVAX-LAMP/Gc, respectively, were constructed. Proteins of interest were identified by fluorescence microscopy following cell line transfection. Five groups of 20 female BALB/c mice were subjected to the following inoculations: inactivated HTNV vaccine, pVAX-LAMP/Gc, pVAX-Gc, and, as the negative controls, pVAX-LAMP or the blank vector pVAX1. Humoral and cellular immunity were assessed by enzyme-linked immunosorbent assays (ELISAs) and 15-mer peptide enzyme-linked immunospot (ELISpot) epitope mapping assays. Repeated immunization with pVAX-LAMP/Gc enhanced adaptive immune responses, as demonstrated by the specific and neutralizing antibody titers and increased IFN-γ production. The inactivated vaccine induced a comparable humoral reaction, but the negative controls only elicited insignificant responses. Using a mouse model of HTNV challenge, the in vivo protection conferred by the inactivated vaccine and Gc-based constructs (with/without LAMP recombination) was confirmed. Evidence of pan-epitope reactions highlighted the long-term cellular response to the LAMP-targeting strategy, and histological observations indicated the safety of the LAMP-targeting vaccines. The long-term protective immune responses induced by pVAX-LAMP/Gc may be due to the advantage afforded by lysosomal targeting after exogenous antigen processing initiation and major histocompatibility complex (MHC) class II antigen presentation trafficking. MHC II-restricted antigen recognition effectively primes HTNV-specific CD4+ T-cells, leading to the promotion of significant immune responses and immunological memory. An epitope-spreading phenomenon was observed, which mirrors the previous result from the Gn study, in which the dominant IFN-γ-responsive hot-spot epitopes were shared between HLA-II and H2d. Importantly, the pan-epitope reaction to Gc indicated that Gc should be with potential for use in further hantavirus DNA vaccine investigations.

Hypoxia upregulates HIG2 expression and contributes to bevacizumab resistance in glioblastoma.

Hypoxia contributes to the maintenance of stem-like cells in glioblastoma (GBM), and activates vascular mimicry and tumor resistance to anti-angiogenesis treatments. The present study examined the expression patterns and biological significance of hypoxia-inducible protein 2 (HIG2, also known as HILPDA) in GBM. HIG2 was highly expressed in gliomas and was correlated with tumor grade, and high HIG2 expression independently predicted poor GBM patient prognosis. HIG2 was upregulated during hypoxia and by hypoxia mimics, and HIG2 knockdown in GBM cells inhibited cell proliferation and invasion. HIF1α bound to the HIG2 promoter and increased its expression in GBM cells, and HIG2 upregulated HIF1α expression. Reconstruction of a HIG2-related molecular network using bioinformatics methods revealed that HIG2 is closely correlated with angiogenesis genes, such as VEGFA, in GBM. HIG2 levels positively correlated with VEGFA in GBM samples. In addition, treatment of transplanted xenograft nude mice with bevacizumab (anti-angiogenesis therapy) resulted in HIG2 upregulation at late stages. We conclude that HIG2 is overexpressed in GBM and upregulated by hypoxia, and is a potential novel therapeutic target. HIG2 overexpression is an independent prognostic indicator and may promote tumor resistance to anti-angiogenesis treatments.

Domestication and geographic origin of Oryza sativa in China: insights from multilocus analysis of nucleotide variation of O. sativa and O. rufipogon.

Previous studies have indicated that China is one of the domestication centres of Asian cultivated rice (Oryza sativa), and common wild rice (O. rufipogon) is the progenitor of O. sativa. However, the number of domestication times and the geographic origin of Asian cultivated rice in China are still under debate. In this study, 100 accessions of Asian cultivated rice and 111 accessions of common wild rice in China were selected to examine the relationship between O. sativa and O. rufipogon and thereby infer the domestication and evolution of O. sativa in China through sequence analyses of six gene regions, trnC-ycf6 in chloroplast genomes, cox3 in mitochondrial genomes and ITS, Ehd1, Waxy, Hd1 in nuclear genomes. The results indicated that the two subspecies of O. sativa (indica and japonica) were domesticated independently from different populations of O. rufipogon with gene flow occurring later from japonica to indica; Southern China was the genetic diversity centre of O. rufipogon, and the Pearl River basin near the Tropic of Cancer was the domestication centre of O. sativa in China.

Simple sequence repeat analysis of genetic diversity in primary core collection of peach (Prunus persica).

In this study, the genetic diversity of 51 cultivars in the primary core collection of peach (Prunus persica (L.) Batsch) was evaluated by using simple sequence repeats (SSRs). The phylogenetic relationships and the evolutionary history among different cultivars were determined on the basis of SSR data. Twenty-two polymorphic SSR primer pairs were selected, and a total of 111 alleles were identified in the 51 cultivars, with an average of 5 alleles per locus. According to traditional Chinese classification of peach cultivars, the 51 cultivars in the peach primary core collection belong to six variety groups. The SSR analysis revealed that the levels of the genetic diversity within each variety group were ranked as Sweet peach > Crisp peach > Flat peach > Nectarine > Honey Peach > Yellow fleshed peach. The genetic diversity among the Chinese cultivars was higher than that among the introduced cultivars. Cluster analysis by the unweighted pair group method with arithmetic averaging (UPGMA) placed the 51 cultivars into five linkage clusters. Cultivar members from the same variety group were distributed in different UPGMA clusters and some members from different variety groups were placed under the same cluster. Different variety groups could not be differentiated in accordance with SSR markers. The SSR analysis revealed rich genetic diversity in the peach primary core collection, representative of genetic resources of peach.

[The PLS calibration model optimization and determination of rice protein content by near-infrared reflectance spectroscopy].

A hundred and ninety one representative brown rice samples from the Chinese Rice Genebank and the DH population derived from the cross of japonica upland rice IRAT109 with paddy rice Yuefu were selected for this study. Their protein content range was 5.90%-14.50%. Near-infrared diffusive spectroscopy (NIDRS) and partial least square (PLS) were used to determine protein content with different wavelength ranges and data preprocessing methods for regression and information extraction. The object function [R/(1+RMSECV)] of quantitative model was defined, and the samples of calibration and validation tests were classified by projective distribution of PLS loadings. These methods were applied to the optimization of the calibration model. It is demonstrated that the calibration model developed by the spectral data pretreatment of the first derivative + standard vector normalization with the same spectral region (5 000-9 000 cm(-1) resulted in the best determination of protein content in brown rice when the maximum values of the object function were reached. The maximum values of the object functions of calibration and validation sets were 0.701 and 0.687, respectively. Projective distributions of PLS loadings were used to validate the models, and the result was the same as that of validating model by object function [R/(1+RMSECV)].

[QTL analysis for lodging resistance in rice using a DH population under lowland and upland ecosystems].

A DH (doubled haploid) population derived from a cross between Japonica upland rice IRAT109 and Japonica paddy rice Yuefu,was used in this study. Three culm traits, basal culm thickness(BCT), culm length (CL) and culm strength (CS), of DH lines and their parents under upland and lowland ecosystems at milk stage were studied. There were very significant positive correlations between BCT and CL, between BCT and CS and between CL and CS. Data from upland and lowland ecosystems were analyzed respectively and jointly, based on a constructed molecular linkage map(including 94 RFLP markers and 71 SSR markers and covering 1 535. 1cM)and the software QTLmapper version 1.0. A total of nine additive QTLs and five pairs of epistatic QTLs associated with BCT, CL, and CS were found by data analysis respectively. Six additive QTLs and six pairs of epistatic QTLs associated with BCT and CL were detected by data analysis jointly. Six additive QTLs and one pair of epistatic QTLs were detected by both methods. Two additive QTLs and two pairs of epistatic QTLs ( bct1a, c/9, c/6a-c/6c and cs5-cs12) for culm traits with general contributions of over 30% to phenotypic variation might be useful for upland rice lodging resistance molecular breeding under upland ecosystem.

[Genetic diversity of common wild rice (Oryza rufipogon Griff) by using SSR markers and phenotypic traits in Guangxi Province].

In this paper, allelic variation and genetic diversity among geographies and growth habit types were studied by using 223 accessions of common wild rice primary core collection in Guangxi Province, with 34 SSR primers locating on 12 chromosomes of rice and 19 phenotypic traits. In the results, 24.91 alleles were detected per locus on average with a range from 7 to 48. Compared to the cultivated rice, the wild rice showed more allelic variations. The ratio of heterozygote of SSR locus was 32.01% on average, and it's range was 1.35% 81.31%. The frequency of heterozygote of SSR locus in Oryza rufipogon Griff was much higher than in Oryza sativa L. The geographical distribution of genetic diversity measured by SSR markers was not completely accordant with that by phenotypic traits. At DNA level, more wild rice individuals and higher genetic diversity were included within the area covering north latitude 22 degrees - 23 degrees and 23 degrees - 24 degrees (comprising Longan, Fusui, Yongning, Xiangzhou, Laibin, Xuanwu, Yulin and Guigang county), which formed the center of genetic diversity. But the center of genetic diversity at the phenotypic level located within north latitude 21 degrees - 22 degrees and 22 degrees - 23 degrees. Among the four growth habit types, the genetic diversity from high to low was found respectively in prostrate type, sloping type, slighting type, and erect type at both DNA and phenotypic levels.