In this study, we formulate a rapid, scalable and reproducible in vitro model of 3D MTS for drug screening purposes, and the cytotoxicity results showed an enhanced 5-FU resistance of HeLa carcinoma cells in 3D MTSs than 2D monolayer culture.In order to reveal the molecular mechanisms that drive 5-FU resistance in 3D HeLa carcinoma cells, a multi-omics study was applied to discover hidden biological regularities. We found that in the 3D MTSs mitochondrial function-related proteins and the metabolites of the tricarboxylic acid cycle were significantly decreased, and the cellular metabolism was shifted towards glycolysis. The differences in the protein synthesis, processing, and transportation between 2D monolayer cultures and 3D MTSs was significant, mainly in the heat shock protein family, with the upregulation of protein folding function in endoplasmic reticulum, which promoted the maintenance of ER homeostasis in the 3D MTSs. In addition, at the transcript and protein level, the expression of extracellular matrix proteins (e.g., laminin and collagen) were up-regulated in the 3D MTSs, which enhanced the physical barrier of drug penetration.

In this study, the effect of sodium tungstate on aerobic digestion of waste sewage sludge (WSS) was investigated. Interestingly, enhanced methane production was found according to the increased concentration of sodium tungstate to WSS. Acidogenesis stage was influenced by sodium tungstate because the amount of acetate decreased whereas that of isobutyrate increased during the anaerobic digestion of WSS supplemented with sodium tungstate. Since acetate consumed with time during the anaerobic digestion of WSS, the pH of WSS increased in the presence of sodium tungstate. The analyses of methanogenesis via acetoclastic and hydrogentrophic methanogens indicate that methane production from acetate was high in the WSS with sodium tungstate. In addition, the addition of sodium tungstate to the initial fresh WSS did not enhance methane production from acetate; therefore, sodium tungstate may increase the number of acetoclastic methanogens rather than promote the catalytic reaction related to the methane production. The analyses of archaeal population supported that acetoclastic methanogens (mostly Methanosaeta) increased from 3.02% to 31.20% in the presence of sodium tungstate. Furthermore, the addition of sodium tungstate enhanced the growth of Methanosarcina acetivorans C2A. Taken together, sodium tungstate increases methane production via the anaerobic digestion of WSS by increasing the activity of acetoclastic methanogenesis.

SARS coronavirus 2 (SARS-CoV-2) in the viral spike (S) encoding a SARS-COV-2 SPIKE D614G mutation protein predominate over time in locales revealing the dynamic aspects of its key viral processes where it is found, implying that this change enhances viral transmission. In this paper, we strongly combine topology geometric methods for generalized formalisms of k-nearest neighbors as a Tipping–Ogilvie and Machine Learning application within the quantum computing context targeting the atomistic level of the protein apparatus of the SARS-COV-2 viral characteristics. In this effort, we propose computer-aided rational drug design strategies efficient in computing docking usage, and powerful enough to achieve very high accuracy levels for this in-silico effort for the generation of AI-Quantum designed molecules of GisitorviffirnaTM, Roccustyrna_gs1_TM, and Roccustyrna_fr1_TM ligands targeting the COVID-19-SARS-COV-2 SPIKE D614G mutation by unifying Molecular Pairs (MMP), Lindenbaum-Tarski logical spaces and Adaptive Weighted KNN Positioning for Matched Bemis and Murko (BM) driven eigenvalue statements into Shannon entropy quantities as composed by Tipping–Ogilvie driven Machine Learning potentials on a (DFT) ℓneuron(ι):=φ∘D∘R2∘S∘R1 02(1+∑=1{−ℏ20<≡===〈ψ⁎∣∣ψ⁎〉=∑Ni,j=1⟨ψi∣∣(ˆ−ρˆ0)∣∣ψj⟩∑Ni,j=1δij−∑Ni,j=1⟨ψi∣∣ρˆ0∣∣ψj⟩N−Tr[ρˆρˆ0]−∑Ni=1,j≠i⟨ψi∣∣ρˆ0∣∣ψj⟩1−2ℜ∑Ni=1,j

Objective The immune responses of COVID-19 convalescent patients have not been well described. Methods Blood from thirty COVID-19 convalescent patients who were virus-free were collected. Their clinical laboratory findings and SARS-CoV-2-specific humoral and cellular immunity were detected. Results At 283 days after diagnosis of SARS-CoV-2 infection, the levels of clinical laboratory indicators and lymphocyte subtypes returned to normal levels. However, the ratio of memory/naive CD4+ T lymphocytes cells was greater in COVID-19 convalescent patients and severe COVID-19 convalescent patients, when compared with that in healthy blood donors (P=0.0135) and non-severe patients (P=0.0431), respectively. The levels of anti-SARS-CoV-2-IgM (P=0.014), S1-IgM (P=0.0004) and RBD-IgM (P=0.0002) in severe COVID-19 patients were all significantly greater than those in non-severe COVID-19 patients. When the serums of COVID-19 convalescent patients were diluted as 1:125, the predictive of serum neutralization capabilities were persistent in all patients. SARS-CoV-2-specific T cells were generated and maintained in majority of tested convalescent COVID-19 patients, regardless of the severity of disease in acute phase. Conclusion At 283 days after diagnosis of SARS-CoV-2 infection, specific cellular and humoral immunity against SARS-CoV-2 could be detectable. The severity of disease in acute phase cannot affect the strength of cellular and humoral immunity in convalescent phase.

BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmissible among people，and the critical cases are still tough to treat, even leading to death. METHODS We retrospectively collected the clinical data of all the critical patients admitted to the Three Gorges Hospital(Chongqing, China) from Jan 20, 2020 to Feb 16, 2020 , whom were divided into improved group and worsen group. At last, we analyzed and compared the differences in laboratory indexes and length of hospital stay of the two groups. RESULT 46 cases were enrolled in the study. Comorbid conditions were present in 25 cases (54.3%). Most cases had symptoms, such as fever, cough, sputum, shortness of breath and dyspnea. The worsen group had a higher APACHE II score of 14(range from 5 to 23) than improved group(5, range from 3 to 7)(p<0.05). 32(69.6%) cases had low level lymphocyte counts (<1.0×109/L), including 8(66.7%) worsen group patients and 24(70.6%) improved group patients. The worsen group was 14.3(range from 8.21 to 18) with the ratio of neutrophil counts to lymphocyte counts, higher than that in improved group((7.33, range from 4.71 to 14.35)(p<0.05). There were faster respiratory frequencies in worsen group(23, range from 20 to 24.75) (p<0.05). And the worsen group had a lower OI(156.5, range from 74.25 to 233) than the other group(206, range from 177.5 to 242.75)(p<0.05). CONCLUSIONS Initial lower lymphocytes and higher APACHE II scores might be relative to the poor prognosis. And most of severe or critical patients had underlying diseases.

Interleukin-11 is a pleiotropic cytokine that is known to play an important role in the progression of various forms of cancer by modulating the survival and proliferation of tumour cells. IL11 also demonstrates a structural homology to IL6 - the predominant cytokine involved in COVID-19. This makes IL11 a potential therapeutic target in both diseases. This study aimed to evaluate the impact of two mutations- R135E and R190E on the stability of IL11. Any changes in the interaction of IL11 with its receptor IL11Rα, induced by the two mutations were also determined with the help of techniques such as molecular modelling, molecular docking, and molecular dynamics simulations. Our analysis revealed that the two mutations cause a small decrease in the overall stability of IL11, which was evident by the increased atomic fluctuations in the mutated regions. Moreover, mutation R135E led to an increase in the binding affinity of IL11 with IL11Rα and the formation of a more stable complex in comparison to the wild-type protein and its receptor. Mutation R190E led to the formation of a less stable complex than the wild-type which suggests a decrease in the binding affinity between IL11 and IL11Rα.

Background Multiple sclerosis is a chronic autoimmune inflammatory demyelinating disorder of the central nervous system. The clinical presentation supported by characteristic findings on MRI forms the backbone of the current diagnostic criteria. This study was aimed to investigate the efficacy based on MRI outcomes of FDA approved disease-modifying therapies (DMTs) for relapsing-remitting MS (RRMS). Materials and Methods We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCTs) of DMTs. The outcome measures were the change from baseline in the number of T2, T1 and/or gadolinium-enhancing (Gd+) lesions in brain MRI performed at 12 months to 24 months. We performed a network meta-analysis using the frequentist approach in STATA version 16.0. Results We identified 26 RCTs for final analysis. Interferon β-1a and placebo were the most common comparison treatment. Dimethyl fumarate (DMF) 480 mg was more effective in reducing the Gd+ lesions and T1 lesions. Pegylated interferon β1a 250 mcg was relatively better in reducing T2 lesions. The treatment ranking showed that DMF 480 mg/720 mg and interferon β1b 250 mcg were more efficacious (0.9, 0.8 and 0.8 in SUCRA, respectively) for Gd+ lesions; pegylated interferon β1b 250 mcg and DMF 480 mg/720 mg were more efficacious (1.0, 0.9 and 0.9 in SUCRA, respectively) for T2 lesions and dimethyl fumarate 480 mg/720 mg were more effective (0.9 in SUCRA both, respectively) for T1 lesions. Conclusion Dimethyl fumarate 480 mg and pegylated interferon β1a 250 mcg demonstrated favourable MRI outcomes in patients with the RRMS

Seamless modification of bacteria chromosome is widely performed both in theoretical and in practical research, such as functional genome analysis and metabolic engineering. For this purpose, excellent counter-selection marker genes with high selection stringency are urgent needed. Lysis gene E from bacteriophage PhiX174, which is of universal and powerful killing effect on Gram-negative strains, was developed and optimized as a generic counter-selection marker in this paper. Lysis gene E was firstly constructed under the control of pL promoter. At high temperature such as 42 °C, inducible expression of Lysis gene E could effectively promote the death of Escherichia coli MG1655. Seamless modification using E as a counter-selection marker also successfully conducted with high ration of positive recombinants. It also works in another Gram-negative strain Serratia marcescens under the control of Arac/PBAD regulatory system. Through combining lysis gene E and kil, the selection stringency frequency of pL-kil-sd-E cassette in E. coli arrived at 4.9×10−8 and 3.2×10−8 at two test loci, which is very close to the best counter-selection system, inducible toxins system. Under the control of Arac/PBAD, selection stringency of PBAD-kil-sd-E in S. marcescens arrived mostly at the level of 10−7 at four test loci. By introducing araC gene harboring plasmid pKDsg-ack, 5- to 18- fold improvement of selection stringency was observed at all these loci, and a surprising low selection stringency frequency 4.9×10−9 was obtained at marR-1 locus. This is the lowest selection stringency frequency for counter-selection reported so far. Similarly, at araB locus of E. coli selection stringency frequency of PBAD-kil-sd-E was improved 170- fold to 3×10−9 after introducing plasmid pKDsg-ack. In conclusion, we have developed and optimized a newly universal counter-selection marker based on lysis gene E. The best selection stringency of this new marker exceeds the inducible toxins system several fold. We provide a valuable counter-selection marker with high selection stringency to the genome editing toolbox.

A document by Yeshey Dorjey. Click on the document to view its contents.

Nitrogen (N) or phosphorus (P) bioavailability constrain the magnitude of terrestrial carbon uptake and plant growth in tropical and subtropical regions, while carbon metabolism is coupled with plant hydraulic systems; therefore, nutrient availability changes are likely to exacerbate or alleviate drought-induced plant mortality. Most studies have neglected the hydraulic failure risk degree and are limited to single species fertilization experiments. We aimed to fill this gap by examining how variation in the relative P availability to N, as reflected by foliar N:P ratios, influences plant hydraulic failure risk degree across a broad range of species by collecting published data and conducting field experiments. The results demonstrated that increasing relative P availability to N would decrease the hydraulic safety margin (increase hydraulic failure risk) by regulating the leaf area: stem area ratio and changing vessel wall reinforcement. This study suggests that forests would potentially face increasing drought-induced mortality if relative P availability is increased through human activities including fertilization, while the mortality risk would decrease with a decrease in relative P availability due to heavy N deposition in tropical and subtropical regions. Relative P availability should be considered when assessing the forests vulnerability to global change.

Monogenean infection of the internal organs is extremely rare when compared to external infections. This study describes mass mortality of Nile tilapia ( Oreochromis niloticus L.) originating from co-infection with Enterogyrus spp. and Aeromonas jandaei following transport stress. The first fish deaths occurred on day 1 post-transport, while cumulative mortality reached approximately 90% by day 10 post-stocking. An atypical amount of pale (whitish) faeces floating on the surface of the water as well as typical clinical signs of motile Aeromonas septicemia, were reported. Adult monogeneans and countless eggs of monogeneans were found in the stomachs and the intestines of both moribund and dead fish, respectively. Two strains of A. jandaei were isolated from the kidneys. Scanning electron microscope microphotographs of the stomach revealed the presence of numerous monogeneans penetrating deep into the gastric tissue, and diffuse lesions filled with bacilliform bacteria. Histopathological examination showed multifocal eosinophilic infiltrate, gastric gland and epithelial necrosis with sloughed necrotic debris in the lumen. This is the first report of co-infection by Enterogyrus spp. and A. jandaei in Nile tilapia and the first report of E. coronatus, E. foratus, and E. malbergi parasitizing tilapia in Brazil. These findings indicate that synergic co-infection by Monogenean stomach parasites ( E. coronatus, E. foratus, and E. malbergi) and A. jandaei may induce high mortalities in tilapia following transport stress.

Objective: The present study aimed to evaluate the extent of family physicians’ anxiety about the viral epidemic and work-related stress associated with the viral epidemic as well as examining the effects of COVID-19 vaccination on such situations. Methods: The data collection forms, including SAVE-9 scale in order to assessand examine the extent of anxiety and stress, prepared for this cross-sectional study were converted into an online questionnaire form and sent to the physicians working as family physicians in different provinces of Turkey between December 2020 - March 2021 via e-mails and communication groups. The responses of 500 family physicians, who were accessible through this method and volunteered to participate in the study, were recorded to be analysed. Results: Of all the 500 family physicians in this study, 40.6% of them were found to be in a state of anxiety about the viral epidemic. While there was a significant decline in the scores of anxiety about the viral epidemic in the subgroup after vaccination, there was no statistically significant change in work-related stress scores. Conclusion: Family physicians have been suffering anxiety due to the pandemic. The vaccination has a positive impact on anxiety.

Although programmed cell death protein-1 (PD-1) is expressed on CD4+ T, CD8+ T and B cells, the T cell expression of PD-1 and macrophages’ expression of its ligands- PD-L1 and PD-L2 increase during leishmaniasis. The PD-1/PD-L1 interaction induces T cell anergy, T cell apoptosis and exhaustion, diversion of T cells toward TH2 and T-reg cells and inhibition of M1 macrophage activities by suppression of nitric oxide (NO) and reactive oxygen species (ROS) production. These changes exacerbate Leishmania infection. As PD-L1-deficient, but not PD-L2-deficient, mice were protected against L. mexicana infection, differential roles have been proposed for PD-L1 and PD-L2 in mouse models of leishmaniasis. Blockade of PD-1/PD-L1 interaction in various in vitro and Leishmania-infected mouse, hamster and dog models enhanced IFN-γ and NO production, reduced IL-10 and TGF-β generation, promoted T cell proliferation and decreased parasite burden. Blockage of PD-1/PD-L1 axis can be considered as a potential therapeutic strategy to restore protective immunity during leishmaniasis, particularly in drug-resistant cases.

Background: Psoriasis is a relapsing chronic inflammatory skin disease where Treg cells appeared to be impaired. CD4+CD25+FoxP3+Treg cells play vital role in immune tolerance. Upon peripheral activation its functional capacity can be altered. Transcription factor Foxp3 is the accepted marker of Treg cell, but it cannot be used to isolate cells for functional studies. Among different functional markers, CD127 (IL-7Rα) a surface marker of activated T cell can be used to see the functional status of CD4+CD25+FoxP3+Treg cells. Aim: The aim of the study was to provide an overview of the immune phenotype of Treg cells in peripheral blood of psoriasis patient with respect to healthy control, and to analyze their association with disease severity and duration. Materials and methods: This cross-sectional study comprising 35 psoriasis patients and 35 healthy controls. Demographical details were recorded, and severity was assessed by Psoriasis Area and Severity Index (PASI) scoring. Peripheral blood mononuclear cells were separated by Ficoll-Hypaque density centrifugation and circulating Treg cells were quantified by flowcytometric immunophenotyping. Results: Increased circulatory CD4+CD25+FoxP3+Treg and CD4+CD25+FoxP3+CD127+/pTreg and decreased CD4+CD25+FoxP3+CD127-/tTreg cells were seen in psoriasis patients. CD4+CD25+FoxP3+ cells increased only with disease severity whereas CD4+CD25+FoxP3+CD127-/tTreg tends to increase with both disease severity and duration. Conclusion: These findings suggest that accumulation of peripherally activated dysfunctional regulatory cells contribute to pathology of psoriasis, which in turn supports the autoimmune model of disease pathogenesis. It will not only help to evaluate patients’ status more preciously but also pave novel ways for immune therapy.

we show that there exists a homeomorphism f between X^* Fan-Gottesman compactification of T_3-topological space (X,τ) and the canonical extension (X ̵̂,(U(β) ) ̵̂ ) of the pre-uniform space (X,U(β)). Therefore we also showed that X^* Fan-Gottesman compactification T_3-topological space (X,τ) can be viewed as the completion of certain pre-uniform space (X,U(β)).

Hainan Island in south China is a key part of the globally important Indo-Burma biodiversity hotspot, while the origin and maintenance of its species richness remains largely unexplored. In this study, we combined nuclear ITS and cpDNA trnL-trnF and ycf1b sequences to evaluate the genetic structure and phylogeographic patterns of the Hainan-endemic Primulina heterotricha (Gesneriaceae). The results showed significant phylogeographic patterns with low within-population genetic diversity and significant genetic differentiation among populations (Fst = 0.708 ± 0.319 and 0.826 ± 0.209 for nrDNA and cpDNA). Three clades were identified with little gene flow (Nm << 1 for nrDNA and cpDNA), which is supported by our STRUCTURE v.2.3.4 analyses. Our analyses detected two vicariance events at c. 0.83 and c. 0.48 Myr, and suggest that these three genetically-separated groups were isolated by two big rivers (Changhua River and Wanglou River), that likely acted as barriers to gene flow. The magnitude of isolation was positively correlated to the size of the rivers, with the greater barrier effect associated with the larger Changhua River. Our results highlight for the first time the critical role of riverine isolation in the patterns of intraspecific evolution of plant populations on Hainan Island.

Aim: Invasive alien species present a serious threat to the world’s ecosystems and livelihoods. The aim of this paper was to review the negative and positive impacts of Prosopis juliflora (Sw.) DC on the Kenyan and Ethiopian Ecosystems. Location: Kenya and Ethiopia Methods: Thirty-one publications were used to write this paper. The articles were identified through keyword searches such as Prosopis juliflora, invasive species, impacts, livelihoods, and ecosystems using google scholar guided by the above-mentioned categories and forward searches of publications that cited relevant articles helped in gathering publications. Results: We found out that Prosopis juliflora was introduced to Kenya and Ethiopia to tackle desertification, to ensure the self-sufficiency of wood products and to conserve water and soil in the semi-arid areas. Years later, this species has turned invasive; although the communities in infested areas have realized some benefits from this tree such as obtaining timber, charcoal, firewood, shelter, livestock feed from its pods; the negative impacts of this tree have far outweighed the positives. Notably, this invasive plant has significantly impacted agricultural and livestock productivity because it invaded the pasturelands and farmlands. For instance, the negative health implications for livestock significantly reduce their productivity. Similarly, this plant has reduced the diversity of the native trees, herbaceous, and grasses because of its ability to outcompete them. Control methods such as biological, mechanical, chemical, and control by utilization have been tried but none have so far been effective in controlling this invasive plant. Main Conclusions: Our results showed that Prosopis juliflora is a serious invader that has a huge potential of invading the arid and semi-arid lands of Kenya and Ethiopia. Therefore, stakeholders at all levels need to put in place integrated management strategies to reduce the spread and the negative impacts of this species.

Aim:The purpose of this study was to determine the host risk factors associated with mortality in COVID-19 patients who are hospitalized for pneumonia, and also, to find a COVID-19 mortality score based on these. Methods:All patients diagnosed as confirmed or probable COVID-19 pneumonia whom hospitalised in our Chest Diseases Education and Research Hospital between March 11, 2020 and October 1,2020 were enrolled. The optimal cut-off values, sensitivity and specificity values and odds ratios to be used in mortality prediction of the novel scoring system created from these parameters were calculated by ROC analysis according to the area under the curve and Youden index. Results:Over 422 patients (n: 51 mortal, n: 371 survivors) univariate regression analysis showed that age, male gender, smoking, comorbidity, and using ACE inhibitor were prognostic host risk factors for COVID-19-related mortality. Using this analysis, a novel scoring model Co-AMSCA (Age, Male, Smoking history, Comorbidity, ACE inh)was established. The cut-off value of this scoring system (including only host risk factors), which determines the mortality risk in patients, was 3.5 points with 88.4% sensitivity and 65.5 % specificity (AUC = 0.761, 95% CI 0.697-0.826, P < .001) (Figure 1). The mortality risk in patients with a Co-AMSCA mortality score above 3.5 points was 7.8 times higher than patients with lower than 3.5 (OR= 7.8; P < .001).In multivariate logistic regression analysis, older age and smoking (smoker/ex-smoker) were found to be important risk factors for mortality (OR = 12.09; 95% CI 2,564-57,054 P =0.004 and OR = 3.1; 95% CI 1,381-7,295; P = 0.007,respectively). Counclusion:We created a simple mortality score, which is easily calculated and does not require laboratory and time.This study showed that by using Co-AMSCA mortality score that has only host risk factors achieved a prediction of mortality in COVID-19 patients who are hospitalized for pneumonia.

The present study has been carried to investigate the interaction and effect of plasma activated water (PAW) on pea seeds. PAW is produced with the interaction of air plasma with water that forms reactive oxygen-nitrogen species in it. Our results with surface morphological study shows that PAW treatment removes the wax from the surface of peas and modifies their hydrophobic surface to hydrophilic. Wettability study shows decrease in water contact angle with seed surface after PAW treatment. Also, PAW treatment improves germination rate, viability index and mean germination time compared to control. Further, the study reveals that the grown plants have higher roots and shoots length, fresh and dry weight, increased chlorophyll ‘a’ and higher sugar and protein concentration compared to control. Although electrolytic and phenolic leakage from pea leaves did not show any significant difference in PAW and control-treated seeds, results obtained from antioxidant analysis clearly show an increased antioxidant enzymatic (SOD, CAT, APX, and POD) activity mainly in the roots in seedlings grown from seeds treated with PAW. However, no significant difference in H2O2 concentration in the pea plant was observed. Hence, our study indicates potential role of seed pre-treatment with PAW to improve germination and plant growth.

Cold stress is a major environmental factor affecting plant growth and development. Although some plants have developed resistance to cold stress, the molecular mechanism underlying it is poorly understood. Here, we identified cold tolerance gene in cotton (Gossypium hirsutum L.) using genome-wide association study (GWAS) with 200 cotton accessions collected from different regions, and identified variations of a short chain alcohol dehydrogenase gene GhSAD1 that response to cold stress. The virus induced gene silencing (VIGS) and Arabidopsis overexpression experiments showed that GhSAD1 roles in cold-stress response.GhSAD1HapB introduction considerably increased cold tolerance in Arabidopsis transgenic plants, whereas GhSAD1HapA plants exhibited cold-sensitive phenotype. GhSAD1HapB silencing plants exhibited a decrease of abscisic acid (ABA) content and overexpression GhSAD1HapB in Arabidopsis increased ABA content. Additionally, we found that GhSAD1HapB regulated cold stress responses through the activity of c-repeat binding factor, which binds to the promoter region of the gene and regulates ABA signalling pathway under cold conditions. Overexpression of GhSAD1HapB induced cold-regulated (COR) genes expression and improved anti-cold metabolites under cold stress. Collectively, the findings of the study contribute to our understanding of the underlying mechanism of GhSAD1 in cold-stress response in cotton. Moreover, GhSAD1 could serve as candidate gene in improving crop stress

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nt that are involved in the pathogenesis and development of various cancers including B cell acute lymphoblastic leukemia (B–ALL). To determine whether lncRNAs are involved in B-ALL, we analyzed the expression profile of lncRNAs and mRNAs in B-ALL. We performed RNA sequencing of 10 non-leukemic blood disease donors and 10 B-ALL patients for Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Interactions among mRNAs were predicted using the STRING database. The RNA-seq data of lncRNAs and mRNAs were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Potential functions of subtype-specific lncRNAs were determined by using coexpression-based analysis on distally (trans-pattern) located protein-coding genes. A total of 1813 differentially expressed genes (DEGs) and 2203 lncRNAs were identified. Moreover, 10 dysregulated lncRNAs and 10 mRNAs were randomly selected, and further assessed by RT-qPCR in vitro. Go and KEGG analysis demonstrated that the differentially expressed mRNAs were most closely associated with myeloid leukocyte activation and in transcriptional misregulation in cancer, respectively. In addition, co-expression analysis demonstrated that these lncRNAs, including MSTRG.27994.3, MSTRG.21740.1, ENST00000456341, MSTRG.14224.1 and MSTRG.20153.1, may mediate the pathogenesis and development of B-ALL via lncRNA-mRNA network interactions. These results showed that several mRNAs and lncRNAs are aberrantly expressed in the bone marrow of B-ALL patients and play potential roles in B-ALL development, and be useful for diagnostic and/or prognostic purposes in pediatric B–ALL.

This article considers the problem of predicting the amount/number of claims that have been incurred but not reported, say IBNR, and reported but not settled, say RBNS. Using the delay probabilities, calculated by the ZIGM distribution, it predicts both IBNR’s and RBNS’ loss reserves and the corresponding mean square error. The practical application of our findings are applied against a real data.

Objectives: Cochlear implant is the only solution of profound sensorineural hearing loss. The round window implant provides minimal injury to the inner ear, and may preserve the residual hearing, and the key to insert the electrode array is to expose the round window, but displaced facial nerve may hinder the visualization of the round window. The aim of the study was to expose the round window and preserve the full function of facial nerve with endoscopic assistant. Design: Cases with variant facial nerve were observed with rigid endoscopy. The locations of round window were assessed by endoscopy and we performed retrofacial approach, or using “suspended” facial nerve technology to expose the round window by shifting the facial nerve posteriorly. Paticipants: Three cases were collected with variant facial nerve, two cases performed retrofacial approach, one case performed “suspended” facial nerve technology. Results: All cases inserted electrode array in round window and preserve the residual hearing, and none of the cases suffered facial nerve injury, chorda tympani nerve injury, misplacement of the electrode array, and other complications. Conclusion: Rigid endoscopy can provide a clear vision of round window, and assistant the electric array insertion during cochlear implant surgery.

In this paper, we discuss the existence of $IS$-asymptotically $\omega$-periodic mild L-quasi-solutions for a class of fractional evolution equations with non-instantaneous impulses. Under a new concept of upper and lower solutions, a new monotone iterative technique is constructed, and the necessary conditions for the existence of extremal coupled mild $L$-quasi-solutions are obtained. Finally, an example is given to illustrate the effectiveness of our theoretical results.