Transcriptomic changes in the microsporidia proliferation and host responses in congenitally infected embryos and larvae.

Congenital infection caused by vertical transmission of microsporidia N. bombycis can result in severe economic losses in the silkworm-rearing industry. Whole-transcriptome analyses have revealed non-coding RNAs and their regulatory networks in N. bombycis infected embryos and larvae. However, transcriptomic changes in the microsporidia proliferation and host responses in congenitally infected embryos and larvae remains unclear. Here, we simultaneously compared the transcriptomes of N. bombycis and its host B. mori embryos of 5-day and larvae of 1-, 5- and 10-day during congenital infection. For the transcriptome of N. bombycis, a comparison of parasite expression patterns between congenital-infected embryos and larva showed most genes related to parasite central carbon metabolism were down-regulated in larvae during infection, whereas the majority of genes involved in parasite proliferation and growth were up-regulated. Interestingly, a large number of distinct or shared differentially expressed genes (DEGs) were revealed by the Venn diagram and heat map, many of them were connected to infection related factors such as Ricin B lectin, spore wall protein, polar tube protein, and polysaccharide deacetylase. For the transcriptome of B. mori infected with N. bombycis, beyond numerous DEGs related to DNA replication and repair, mRNA surveillance pathway, RNA transport, protein biosynthesis, and proteolysis, with the progression of infection, a large number of DEGs related to immune and infection pathways, including phagocytosis, apoptosis, TNF, Toll-like receptor, NF-kappa B, Fc epsilon RI, and some diseases, were successively identified. In contrast, most genes associated with the insulin signaling pathway, 2-oxacarboxylic acid metabolism, amino acid biosynthesis, and lipid metabolisms were up-regulated in larvae compared to those in embryos. Furthermore, dozens of distinct and three shared DEGs that were involved in the epigenetic regulations, such as polycomb, histone-lysine-specific demethylases, and histone-lysine-N-methyltransferases, were identified via the Venn diagram and heat maps. Notably, many DEGs of host and parasite associated with lipid-related metabolisms were verified by RT-qPCR. Taken together, simultaneous transcriptomic analyses of both host and parasite genes lead to a better understanding of changes in the microsporidia proliferation and host responses in embryos and larvae in N. bombycis congenital infection.

Non-coding RNAs identification and regulatory networks in pathogen-host interaction in the microsporidia congenital infection.

BACKGROUND: The interaction networks between coding and non-coding RNAs (ncRNAs) including long non-coding RNA (lncRNA), covalently closed circular RNA (circRNA) and miRNA are significant to elucidate molecular processes of biological activities and interactions between host and pathogen. Congenital infection caused by vertical transmission of microsporidia N. bombycis can result in severe economic losses in the silkworm-feeding industry. However, little is known about ncRNAs that take place in the microsporidia congenital infection. Here we conducted whole-transcriptome RNA-Seq analyses to identify ncRNAs and regulatory networks for both N. bombycis and host including silkworm embryos and larvae during the microsporidia congenital infection. RESULTS: A total of 4,171 mRNAs, 403 lncRNA, 62 circRNAs, and 284 miRNAs encoded by N. bombycis were identified, among which some differentially expressed genes formed cross-talk and are involved in N. bombycis proliferation and infection. For instance, a lncRNA/circRNA competing endogenous RNA (ceRNA) network including 18 lncRNAs, one circRNA, and 20 miRNAs was constructed to describe 14 key parasites genes regulation, such as polar tube protein 3 (PTP3), ricin-B-lectin, spore wall protein 4 (SWP4), and heat shock protein 90 (HSP90). Regarding host silkworm upon N. bombycis congenital infection, a total of 14,889 mRNAs, 3,038 lncRNAs, 19,039 circRNAs, and 3,413 miRNAs were predicted based on silkworm genome with many differentially expressed coding and non-coding genes during distinct developmental stages. Different species of RNAs form interacting network to modulate silkworm biological processes, such as growth, metamorphosis and immune responses. Furthermore, a lncRNA/circRNA ceRNA network consisting of 140 lncRNAs, five circRNA, and seven miRNAs are constructed hypothetically to describe eight key host genes regulation, such as Toll-6, Serpin-6, inducible nitric oxide synthase (iNOS) and Caspase-8. Notably, cross-species analyses indicate that parasite and host miRNAs play a vital role in pathogen-host interaction in the microsporidia congenital infection. CONCLUSION: This is the first comprehensive pan-transcriptome study inclusive of both N. bombycis and its host silkworm with a specific focus on the microsporidia congenital infection, and show that ncRNA-mediated regulation plays a vital role in the microsporidia congenital infection, which provides a new insight into understanding the basic biology of microsporidia and pathogen-host interaction.

Attack Resilient True Random Number Generators Using Ferroelectric-Enhanced Stochasticity in 2D Transistor.

By harnessing the physically unclonable properties, true random number generators (TRNGs) offer significant promises to alleviate security concerns by generating random bitstreams that are cryptographically secured. However, fundamental challenges remain as conventional hardware often requires complex circuitry design, showing a predictable pattern that is susceptible to machine learning attacks. Here, a low-power self-corrected TRNG is presented by exploiting the stochastic ferroelectric switching and charge trapping in molybdenum disulfide (MoS2 ) ferroelectric field-effect transistors (Fe-FET) based on hafnium oxide complex. The proposed TRNG exhibits enhanced stochastic variability with near-ideal entropy of ≈1.0, Hamming distance of ≈50%, independent autocorrelation function, and reliable endurance cycle against temperature variations. Furthermore, its unpredictable feature is systematically examined by machine learning attacks, namely the predictive regression model and the long-short-term-memory (LSTM) approach, where nondeterministic predictions can be concluded. Moreover, the generated cryptographic keys from the circuitry successfully pass the National Institute of Standards and Technology (NIST) 800-20 statistical test suite. The potential of integrating ferroelectric and 2D materials is highlighted for advanced data encryption, offering a novel alternative to generate truly random numbers.

Driver mutations in ADGRL3 are involved in the evolution of ependymoma.

Although there have been recent advances in the molecular pathology of ependymomas, little is known about the underlying molecular evolution during its development. Here, we assessed the clinical, pathological and molecular evolutionary process of ependymoma recurrence in a 9-year-old patient who had seven recurrences of supratentorial ependymoma and died from intracranial multiregional recurrences at the age of 19 years old. Whole-genome sequencing (WGS) of 7 tumor samples (1 primary and 6 subsequent recurrent tumors) was performed to elucidate the mutation landscape and identify potential driver mutations for tumor evolution. The genetic profiles of the seven tumor specimens showed significant heterogeneity and suggested a highly branched evolutionary pattern. The mutational signatures and chromothripsis changed with treatments. Strikingly, adhesion G protein-coupled receptor L3 (ADGRL3, also known as Latrophilins 3, LPNH3) was found to be consistently mutated during the entire disease process. However, Sanger sequencing of other 78 ependymoma patients who underwent surgery at our institution showed no genetic alteration of ADGRL3, as found in the present case. The mRNA levels of ADGRL3 were significantly lower in ependymomas (n = 36), as compared with normal brain tissue (n = 3). Grade III ependymomas had the lowest ADGRL3 expression. Moreover, ependymomas with lower mRNA level of ADGRL3 had shorter overall survival. Our findings, therefore, demonstrate a rare evolutionary process of ependymoma involving ADGRL3.

Improving the cell-membrane-penetrating activity of globins by introducing positive charges on protein surface: A case study of sperm whale myoglobin.

Globins are heme proteins such as hemoglobin (Hb), myoglobin (Mb) and neuroglobin (Ngb), playing important roles in biological system. In addition to normal functions, zebrafish Ngb was able to penetrate cell membranes, whereas less was known for other globin members. In this study, to improve the cell-membrane-penetrating activity of globins, we used sperm whale Mb as a model protein and constructed a quadruple mutant of G5K/Q8K/A19K/V21K Mb (termed 4K Mb), by introduction of four positive charges on the protein surface, which was designed according to the amino acid alignment with that of zebrafish Ngb. Spectroscopic and crystallographic studies showed that the four positively charged Lys residues did not affect the protein structure. Cell-membrane-penetrating essay further showed that 4K Mb exhibited enhanced activity compared to that of native Mb. This study provides valuable information for the effect of distribution of charged residues on the protein structure and the cell-membrane-penetrating activity of globins. Therefore, it will guide the design of protein-based biomaterials for biological applications.

Survival Benefit from Surgical Resection in Lung Cancer Patients with Brain Metastases: a Single-Center, Propensity-Matched Analysis Cohort Study.

BACKGROUND: Brain metastases (BMs) are the most serious complication of lung cancer, affecting the prognosis of lung cancer patients, and pose distinct clinical challenges. This study was designed to explore the prognostic factors related to lung cancer BM and the value of surgical resection in BMs from lung cancer. METHODS: A retrospective analysis was performed on 714 patients with lung cancer BMs screened between January 2010 and January 2018 at the Sun Yat-sen University Cancer Center. A 1:1 propensity score matching analysis was performed to reduce the potential bias between the surgery and the nonsurgery group. In both the raw and the propensity-score matched dataset, univariate and multivariate Cox proportional hazards regression analyses were used to evaluate risk factors for survival. RESULTS: After matching, 258 patients (129 surgery, 129 no surgery) were analyzed. Multivariate analyses after propensity score matching demonstrated that surgical resection was an independent protective factor for overall survival (OS), and older age, lower Karnofsky Performance Scale (KPS) score, and extracranial metastases were independent risk factors for worse OS. Patients without extracranial metastases, without synchronous BM and with a single BM had a better prognosis. CONCLUSIONS: The findings showed that surgical resection, age, KPS score, and extracranial metastases are independent prognostic factors for predicting the OS of patients with lung cancer BMs, and surgical resection for brain metastatic lesions could significantly improve the OS. However, only certain groups of patients with BMs can benefit from intracranial lesion resection, such as no extracranial metastases and metachronous metastases.

The application of fluorescein sodium for the resection of medulloblastoma.

INTRODUCTION: Surgical resection of medulloblastoma (MB) remains a challenge. At present, a variety of tracers have been used for intraoperative tumor visualization. However, there are few reports on the intraoperative visualization of MB. Hence, we reported our experience of applying fluorescein sodium (FS) in MB surgery. METHODS: We retrospectively analyzed the clinical information of patients with MB confirmed by surgery and pathology from January 2016 to December 2020 from Sun Yat-sen University Cancer Center. A total of 62 patients were enrolled, of which 27 received intraoperative FS and 35 did not. The intraoperative dose of FS was 3 mg/kg. RESULTS: Among the 62 patients, 42 were males, and twenty were females. The age of onset in the FS group was 9.588 ± 7.322, which in the non-fluorescein sodium group was 13.469 ± 10.968, p = 0.198. We did not find significant differences in tumor location, tumor size, tumor resection, tumor histology, and preoperative symptoms (hydrocephalus, headache, vomit, balance disorder) between the groups. There was no significant difference in the postoperative symptoms (hydrocephalus, headache, vomiting, balance disorder, and cerebellar mutism). However, patients in the FS group had a relatively low incidence of balance disorder and cerebellar mutism. There was definite fluorescence of tumor in all cases of the FS group, and even the tiny metastatic lesion was visible. No case had side effects related to the use of FS. CONCLUSIONS: FS is safe and effective in MB surgery. Whether the application of FS for surgery can reduce complications remains to be studied in the future.

Genome-Wide Characterization and Comparative Genomic Analysis of the Serpin Gene Family in Microsporidian Nosema bombycis.

Microsporidia are ubiquitous in the environment, infecting almost all invertebrates, vertebrates, and some protists. The microsporidian Nosema bombycis causes silkworms pébrine disease and leads to huge economic losses. Parasite secreted proteins play vital roles in pathogen-host interactions. Serine protease inhibitors (serpins), belonging to the largest and most broadly distributed protease inhibitor superfamily, are also found in Microsporidia. In this study, we characterized 19 serpins (NbSPNs) in N. bombycis; eight of them were predicted with signal peptides. All NbSPN proteins contain a typical conserved serpin (PF00079) domain. The comparative genomic analysis revealed that microsporidia serpins were only found in the genus Nosema. In addition to N. bombycis, a total of 34 serpins were identified in another six species of Nosema including N. antheraeae (11), N. granulosis (8), Nosema sp. YNPr (3), Nosema sp. PM-1 (3), N. apis (4), and N. ceranae (5). Serpin gene duplications in tandem obviously occurred in Nosema antheranae. Notably, the NbSPNs were phylogenetically clustered with serpins from the Chordopoxvirinae, the subfamily of Poxvirus. All 19 NbSPN transcripts were detected in the infected midgut and fat body, while 19 NbSPN genes except for NbSPN12 were found in the transcriptome of the infected silkworm embryonic cell line BmE-SWU1. Our work paves the way for further study of serpin function in microsporidia.

Pioglitazone alleviates cisplatin nephrotoxicity by suppressing mitochondria-mediated apoptosis via SIRT1/p53 signalling.

Pioglitazone (PIO) attenuates cisplatin nephrotoxicity whereas the underlying mechanism remains unknown. Apoptosis is associated with mitochondrial dysfunction and SIRT1 activation can decrease cell apoptosis in cisplatin nephrotoxicity. Therefore, we explored whether the protective effect of PIO in cisplatin nephrotoxicity is achieved by suppressing mitochondria-mediated apoptosis through SIRT1/p53 signalling regulation. Cell viability, apoptosis, survival rate, renal pathology and function were examined. Moreover, we also analysed the expression of SIRT1, Acetyl-p53, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitochondrial permeability transition pore (mPTP) opening, adenosine triphosphate (ATP) and apoptosis-related protein in vivo and in vitro. Pioglitazone treatment significantly increased cell viability, promoted SIRT1-p53 interaction, upregulated Bcl-2 expression, activated SIRT1 and elevated mitochondrial ATP synthesis after cisplatin treatment. However, PIO decreased the generation of ROS, opening of mPTP, dissipation of MMP and translocation of cytochrome c after cisplatin treatment. Pioglitazone also reduced the activation of caspase-3 and caspase-9, lowered the ratio of Bax/Bcl-2, attenuated kidney pathological damage and dysfunction, down-regulated the expression of Acetyl-p53, PUMA-α and Bax and abated cell apoptosis after cisplatin treatment. The SIRT1 inhibitor, EX527, clearly reversed the protective effects of PIO. These results implied PIO attenuated cisplatin nephrotoxicity by suppressing mitochondria-mediated apoptosis through regulating SIRT1/p53 signalling.

Clinical characteristics of 31 hemodialysis patients with 2019 novel coronavirus: a retrospective study.

AIM: Novel coronavirus pneumonia (COVID-19) has become pandemic. It brings serious threat to hemodialysis (HD) patients. Therefore, we carried out a study on the clinical characteristics of HD patients with COVID-19. METHODS: We retrospectively analyzed the data of 31 HD patients with COVID-19. The clinical features of patients include epidemiology, clinical symptoms, laboratory and imaging test, treatment and prognosis. RESULTS: 61.3% were severe, and 38.7% were mild. 83.9% had a close contact history with COVID-19 patients. The average age was 62.3 years comprising of 58.1% men and 41.9% women. Ninety percent had chronic diseases except ESRD. Clinical symptoms include cough (85%), fever (43%), and shortness of breath (48.4%), etc. Complications included ARDS (25.8%), AHF (22.6%), and septic shock (16.1%), etc. 64.5% of patients had remission, and 35.5% of patients had no remission with 6.5% deaths. Compared with the baseline before infection, HD patients with COVID-19 had lower lymphocytes, albumin and glucose, and higher D-dimer, albumin, phosphorus, lactate dehydrogenase, and CRP. There was no significant correlation between the neutrophils/lymphocytes ratio and the severity of the disease. CONCLUSIONS: Compared with the reported general population, the HD patients are susceptible to COVID-19 infection, especially older men and those with other underlying diseases. Moreover, HD patients have more severe infection and inflammation with less symptoms and worse outcome. COVID-19 infection can cause dialysis patients lower immunity, stronger inflammation, malnutrition, and internal environment disorder. Neutrophils/lymphocytes ratio does not reflect the severity of the HD patients with COVID-19.

The Proton Dissociation of Bio-Protic Ionic Liquids: [AAE]X Amino Acid Ionic Liquids.

[AAE]X composed of amino acid ester cations is a sort of typically "bio-based" protic ionic liquids (PILs). They possess potential Brønsted acidity due to the active hydrogens on their cations. The Brønsted acidity of [AAE]X PILs in green solvents (water and ethanol) at room temperature was systematically studied. Various frameworks of amino acid ester cations and four anions were investigated in this work from the viewpoint of structure-property relationship. Four different ways were used to study the acidity. Acid dissociation constants (pKa) of [AAE]X determined by the OIM (overlapping indicator method) were from 7.10 to 7.73 in water and from 8.54 to 9.05 in ethanol. The pKa values determined by the PTM (potential titration method) were from 7.12 to 7.82 in water. Their Hammett acidity function (H0) values (0.05 mol·L-1) were about 4.6 in water. In addition, the pKa values obtained by the DFT (proton-transfer reactions) were from 7.11 to 7.83 in water and from 8.54 to 9.34 in ethanol, respectively. The data revealed that the cationic structures of [AAE]X had little effect and the anions had no effect on the acidity of [AAE]X. At the same time, the OIM, PTM, Hammett method and DFT method were reliable for determining the acidic strength of [AAE]X in this study.

[Experimental studies for noninvasive assessment of portal vein pressure based on contrast enhanced subharmonic sonographic imaging].

Portal hypertension (PHT) is a common complication of liver cirrhosis, which could be measured by the means of portal vein pressure (PVP). However, there is no report about an effective and reliable way to achieve noninvasive assessment of PVP so far. In this study, firstly, we collected ultrasound images and echo signals of different ultrasound contrast agent (UCA) concentrations and different pressure ranges in a low-pressure environment based on an in vitro simulation device. Then, the amplitudes of the subharmonics in the echo signal were obtained by ultrasound grayscale image construction and fast Fourier transform (FFT). Finally, we analyzed the relationship between subharmonic amplitude (SA) and bionic portal vein pressure (BPVP) through linear regression. As a result, in the pressure range of 7.5-45 mm Hg and 8-20 mm Hg, the linear correlation coefficients (LCC) between SA and BPVP were 0.927 and 0.913 respectively when the UCA concentration was 1∶3 000, and LCC were 0.737 and 0.568 respectively when the UCA concentration was 1∶6 000. Particularly, LCC was increased to 0.968 and 0.916 respectively while the SAs of two UCA concentrations were used as the features of BPVP. Therefore, the results show a good performance on the linear relationship between SA and BPVP, and the LCC will be improved by using SAs obtained at different UCA concentrations as the features of BPVP. The proposed method provides reliable experimental verification for noninvasive evaluation of PVP through SA in clinical practice, which could be a guidance for improving the accuracy of PVP assessment.

Assessment of ctDNA in CSF may be a more rapid means of assessing surgical outcomes than plasma ctDNA in glioblastoma.

We aimed to develop a high-throughput deep DNA sequencing assay of cerebrospinal fluid (CSF) to identify clinically relevant oncogenic mutations that contribute to the development of glioblastoma (GBM) and serve as biomarkers to predict patients' responses to surgery. For this purpose, we recruited five patients diagnosed with highly suspicious GBM according to preoperative magnet resonance imaging. Subsequently, patients were histologically diagnosed with GBM. CSF was obtained through routine lumbar puncture, and plasma from peripheral blood was collected before surgery and 7 days after. Fresh tumor samples were collected using routine surgical procedures. Targeted deep sequencing was used to characterize the genomic landscape and identify mutational profile that differed between pre-surgical and post-surgical samples. Sequence analysis was designed to detect protein-coding exons, exon-intron boundaries, and the untranslated regions of 50 genes associated with cancers of the central nervous system. Circulating tumor DNAs (ctDNAs) were prepared from the CSF and plasma from peripheral blood. For comparison, DNA was isolated from fresh tumor tissues. Non-silent coding variants were detected in CSF and plasma ctDNAs, and the overall minor allele frequency (MAF) of the former corresponded to an earlier disease stage compared with that of plasma when the tumor burden was released (surgical removal). Gene mutation loads of GBMs significantly correlated with overall survival (OS, days) (Pearson correlation = -0.95, P = 0.01). We conclude that CSF ctDNAs better reflected the sequential mutational changes of driver genes compared with those of plasma ctDNAs. Deep sequencing of the CSF of patients with GBM may therefore serve as an alternative clinical assay to improve patients' outcomes.

Catalyst-free direct cross-dehydrogenative coupling of imidazoheterocycles with glyoxal hydrates: an efficient approach to 1,2-diketones.

An efficient and convenient methodology for catalyst-free cross-dehydrogenative coupling of imidazoheterocycles with glyoxal hydrates in good yields was developed. This methodology exhibits a broad substrate scope and excellent functional group tolerance and offers a straightforward means to produce different heterocycles such as imidazoheterocyclic quinoxaline, imidazoheterocyclic hydantoin and imidazoheterocyclic α-keto ketamine under relatively mild conditions. Biological evaluation showed that the most potent compound 3m possesses significant in vitro antiproliferative activities against human-derived lung cancer cell lines with an IC50 value of 14.8 µM.

Copper-catalyzed C-H/N-H cross-coupling reactions for the synthesis of 3-heteroaryl quinoxalin-2(1H)-ones.

An effective copper-catalyzed direct C-H/N-H cross-coupling of quinoxalin-2(1H)-ones with diverse unprotected 2-quinoxalinones and 2-quinolinones has been developed. This protocol provides a convenient route, with broad substrate scope, good functional group tolerance, and high atom economy, to various important quinoxalin-2(1H)-one-containing biheteroaryls, which are privileged structures in many biologically active compounds.

Fluorescein sodium-guided biopsy or resection in primary central nervous system lymphomas with contrast-enhancing lesion in MRI.

BACKGROUND: Surgical procedures are critical in making a conclusive histopathological diagnosis of primary central nervous system lymphoma (PCNSL), which typically presents contrast-enhancing lesions in magnetic resonance imaging (MRI). The fluorescein sodium-guided technique could enhance tumor visibility. We reported a series of patients with PCNSL underwent fluorescein sodium-guided surgical procedures. PATIENTS AND METHODS: 12 patients clinically considered brain tumors underwent fluorescein sodium-guided surgery in Sun Yat-sen University Cancer Center from March 2016 to July 2017. The age of 4 female and 8 male patients ranges from 39 to 62 years. In 4 patients, corticosteroid had been prescribed before surgery due to intracranial hypertension. After injection of low dose of sodium fluorescein (3-5 mg/kg), the lesions with strong fluorescence staining were identified as the target area for biopsy or resection. RESULTS: Based on the targeted tissues with bright and homogenous fluorescence staining, all 12 patients were conclusively diagnosed as B cell non-Hodgkin's lymphoma (diffuse large cell). The specificity of the specimens sent for frozen section was 86.4% (19/22). No fluorescein sodium associated side effects were observed. CONCLUSION: Fluorescein sodium guided surgery is an effective and safe tool in biopsy or tumor resection in patients suspicious for PCNSL with preoperative MRI presented contrast-enhanced homogenous lesions. Such technique might still be considered in those patients who have been pretreated with corticosteroid.

Divergence of a Tandem Duplication of Manganese Superoxide Dismutase in Nosema bombycis.

Manganese superoxide dismutase (MnSOD) is a key enzyme in the protection of cells from oxidative stress. A tandem duplication of the MnSOD gene (NbMnSOD1 and NbMnSOD2) in the genome of Nosema bombycis, a parasite of the silkworm Bombyx mori, was previously identified. Here, we compare the protein structures of NbMnSOD1 and NbMnSOD2 and characterize these two proteins in terms of cellular localization, timing of transcription, protein structure, and enzyme activity. Despite a similarity in the primary sequence of NbMnSOD1 and NbMnSOD2, the latter shows a remarkable degree of amino acid sequence difference on the protein's surface and in the active site, where there is a substitution of a phenylalanine for a histidine in NbMnSOD2. Immuno-electron microscopy demonstrates that NbMnSOD1 is present in the cytosol of mature spores, whereas NbMnSOD2 is localized on the polar tube and the spore wall. Immunofluorescence confirms the localization of NbMnSOD2 on the polar tube of the germinated spore. Quantitative measurement of gene expression (qRT-PCR) demonstrates production of both alleles during the first day of infection followed by a dramatic decrease during the second to fourth day of infection. From the fifth day onward, the two alleles show a complementary pattern of expression. The qRT-PCR of the host manganese superoxide dismutase (BmMnSOD) shows a notable increase in transcription upon infection, leading to a three-fold spike by the first day of infection, followed by a decrease in transcription. Measurement of overall MnSOD activity shows a similar peak at day 1 followed by a decrease to a constant rate of enzyme activity. The differences in cellular localization and pattern of gene expression of NbMnSOD2 compared to NbMnSOD1, as well as the differences in protein structure seen for NbMnSOD2 compared to other microsporidial MnSODs, strongly suggest a unique, recently evolved role for NbMnSOD2.

Differences in Codon Usage Bias between Photosynthesis-Related Genes and Genetic System-Related Genes of Chloroplast Genomes in Cultivated and Wild Solanum Species.

Solanum is one of the largest genera, including two important crops-potato (Solanum tuberosum) and tomato (Solanum lycopersicum). In this study we compared the chloroplast codon usage bias (CUB) among 12 Solanum species, between photosynthesis-related genes (Photo-genes) and genetic system-related genes (Genet-genes), and between cultivated species and wild relatives. The Photo-genes encode proteins for photosystems, the photosynthetic electron transport chain, and RuBisCO, while the Genet-genes encode proteins for ribosomal subunits, RNA polymerases, and maturases. The following findings about the Solanum chloroplast genome CUB were obtained: (1) the nucleotide composition, gene expression, and selective pressure are identified as the main factors affecting chloroplast CUB; (2) all these 12 chloroplast genomes prefer A/U over G/C and pyrimidines over purines at the third-base of codons; (3) Photo-genes have higher codon adaptation indexes than Genet-genes, indicative of a higher gene expression level and a stronger adaptation of Photo-genes; (4) gene function is the primary factor affecting CUB of Photo-genes but not Genet-genes; (5) Photo-genes prefer pyrimidine over purine, whereas Genet-genes favor purine over pyrimidine, at the third position of codons; (6) Photo-genes are mainly affected by the selective pressure, whereas Genet-genes are under the underlying mutational bias; (7) S. tuberosum is more similar with Solanum commersonii than with Solanum bulbocastanum; (8) S. lycopersicum is greatly different from the analyzed seven wild relatives; (9) the CUB in codons for valine, aspartic acid, and threonine are the same between the two crop species, S. tuberosum and S. lycopersicum. These findings suggest that the chloroplast CUB contributed to the differential requirement of gene expression activity and function between Photo-genes and Genet-genes and to the performance of cultivated potato and tomato.

Low preoperative prognostic nutritional index predicts poor survival in patients with newly diagnosed high-grade gliomas.

Preoperative prognostic nutritional index (PNI) has been widely demonstrated to predict survival of patients with malignant tumors. Its utility in predicting outcomes in patients with high-grade gliomas (HGG) remains undefined. A retrospective study of 188 HGG patients was conducted. An optimal PNI cut-off value was applied to stratify patients into high PNI (≥52.55, n = 78) and low PNI (<52.55, n = 110) groups. Univariate and multivariate analysis was performed to identify prognostic factors associated with overall survival (OS) and progression free survival (PFS). The resulting prognostic models were externally validated using a demographic-matched cohort of 130 HGG patients. In the training set, PNI value was negatively correlated with age (p = 0.027) and tumor grade (p = 0.048). Both PFS (8.27 vs. 20.77 months, p < 0.001) and OS (13.57 vs. 33.23 months, p < 0.001) were significantly worse in the low PNI group. Strikingly, patients in high PNI group had a 52% decrease in the risk of tumor progression and 55% decrease of death relative to low PNI. Multivariate analysis further demonstrated PNI as an independent predictor for PFS (HR = 0.62, 95% CI 0.43-0.87) and OS (HR = 0.56, 95% CI 0.38-0.80). The PNI retained independent prognostic value in the validation set for both PFS (p = 0.013) and OS (p = 0.003). On subgroup analysis by tumor grade and treatment modalities, both PFS and OS were better for the patients with high PNI. The PNI is a potentially valuable preoperative marker for the survival of patients following HGG resection.

Comparative Analysis of the Proteins with Tandem Repeats from 8 Microsporidia and Characterization of a Novel Endospore Wall Protein Colocalizing with Polar Tube from Nosema bombycis.

As a common feature of eukaryotic proteins, tandem amino acid repeat has been studied extensively in both animal and plant proteins. Here, a comparative analysis focusing on the proteins having tandem repeats was conducted in eight microsporidia, including four mammal-infecting microsporidia (Encephalitozoon cuniculi, Encephalitozoon intestinalis, Encephalitozoon hellem and Encephalitozoon bieneusi) and four insect-infecting microsporidia (Nosema apis, Nosema ceranae, Vavraia culicis and Nosema bombycis). We found that the proteins with tandem repeats were abundant in these species. The quantity of these proteins in insect-infecting microsporidia was larger than that of mammal-infecting microsporidia. Additionally, the hydrophilic residues were overrepresented in the tandem repeats of these eight microsporidian proteins and the amino acids residues in these tandem repeat sequences tend to be encoded by GC-rich codons. The tandem repeat position within proteins of insect-infecting microsporidia was randomly distributed, whereas the tandem repeats within proteins of mammal-infecting microsporidia rarely tend to be present in the N terminal regions, when compared with those present in the C terminal and middle regions. Finally, a hypothetical protein EOB14572 possessing four tandem repeats was successfully characterized as a novel endospore wall protein, which colocalized with polar tube of N. bombycis. Our study provided useful insight for the study of the proteins with tandem repeats in N. bombycis, but also further enriched the spore wall components of this obligate unicellular eukaryotic parasite.