Riesz transform on manifolds with ends of different volume growth for 1<p<21<p<2

Let $M_1$, $\cdots$, $M_\ell$ be complete, connected and non-collapsed manifolds of the same dimension, where $2\le \ell\in\mathbb{N}$, and suppose that each $M_i$ satisfies a doubling condition and a Gaussian upper bound for the heat kernel. If each manifold $M_i$ has volume growth either bigger than two or equal to two, then we show that the Riesz transform \nabla \L^{-1/2} is bounded on $L^p(M)$ for each $1<p<2$ on the gluing manifold $M=M_1\#M_2\#\cdots \# M_\ell$.Comment: 38p

Ferroptosis as a promising therapeutic strategy for melanoma

Malignant melanoma (MM) is the most common and deadliest type of skin cancer and is associated with high mortality rates across all races and ethnicities. Although present treatment options combined with surgery provide short-term clinical benefit in patients and early diagnosis of non-metastatic MM significantly increases the probability of survival, no efficacious treatments are available for MM. The etiology and pathogenesis of MM are complex. Acquired drug resistance is associated with a pool prognosis in patients with advanced-stage MM. Thus, these patients require new therapeutic strategies to improve their treatment response and prognosis. Multiple studies have revealed that ferroptosis, a non-apoptotic form of regulated cell death (RCD) characterized by iron dependant lipid peroxidation, can prevent the development of MM. Recent studies have indicated that targeting ferroptosis is a promising treatment strategy for MM. This review article summarizes the core mechanisms underlying the development of ferroptosis in MM cells and its potential role as a therapeutic target in MM. We emphasize the emerging types of small molecules inducing ferroptosis pathways by boosting the antitumor activity of BRAFi and immunotherapy and uncover their beneficial effects to treat MM. We also summarize the application of nanosensitizer-mediated unique dynamic therapeutic strategies and ferroptosis-based nanodrug targeting strategies as therapeutic options for MM. This review suggests that pharmacological induction of ferroptosis may be a potential therapeutic target for MM

Effect of a Traditional Chinese Medicine combined therapy on adolescent idiopathic scoliosis: a randomized controlled trial

AbstractObjectiveTo evaluate the effectiveness of a combined Traditional Chinese Medicine (TCM) therapy versus conventional treatment on adolescent idiopathic scoliosis.MethodsOne hundred twenty outpatients with mild and moderate adolescent idiopathic scoliosis were randomly divided into a TCM group (TCMG) and a brace group (CG). TCMG patients underwent Daoyin, Tuina, and acupotomology therapies. CG patients were treated with a Milwaukee brace. Each patient's Cobb angle was measured after 12 and 24 months of treatment, and pulmonary function was determined after 12 months of treatment. Average electromyogram (AEMG) ratio of the surface electromyogram was measured after 6 and 12 months of treatment and followed-up after 18 and 24 months.ResultsThe Cobb angle significantly decreased in both groups after 12 months of treatment compared with before treatment (P < 0.05). The percentages of original Cobb angle in TCMG and CG were 51.4% and 47.8% (P > 0.05) after 12 months and 62.5% and 34.7% (P < 0.05) after 24 months, respectively. Pulmonary function significantly improved after 12 months in TCMG (P < 0.05) but significantly decreased in CG (P < 0.05). The AEMG ratio was significantly lower (P < 0.01) and tended to remain at 1 after stopping treatment in TCMG, but increased in CG (P < 0.05).ConclusionTCM combined therapy can prevent the progression of scoliosis. The AEMG ratio is a promising index that could replace radiography in the evaluation of treatment effect and progression in scoliosis

Fabrication of ultrahigh-density nanowires by electrochemical nanolithography

An approach has been developed to produce silver nanoparticles (AgNPs) rapidly on semiconductor wafers using electrochemical deposition. The closely packed AgNPs have a density of up to 1.4 × 1011 cm-2 with good size uniformity. AgNPs retain their shape and position on the substrate when used as nanomasks for producing ultrahigh-density vertical nanowire arrays with controllable size, making it a one-step nanolithography technique. We demonstrate this method on Si/SiGe multilayer superlattices using electrochemical nanopatterning and plasma etching to obtain high-density Si/SiGe multilayer superlattice nanowires

NFIX Circular RNA Promotes Glioma Progression by Regulating miR-34a-5p via Notch Signaling Pathway

Objective: The present study aimed to explore the association between NFIX circular RNA (circNFIX) and miR-34a-5p in glioma. Furthermore, this study investigated the influence that circNFIX has on glioma progression through the upregulation of NOTCH1 via the Notch signaling pathway by sponging miR-34a-5p.Methods: We applied five methods, CIRCexplorer2, circRNA-finder, CIRI, find-circ and MapSplice2, to screen for circRNAs with differential expression between three glioma tissue samples and three paired normal tissue samples. The GSEA software was used to confirm whether significantly different pathways were activated or inactivated in glioma tissues. The binding sites between circNFIX and miR-34a-5p were confirmed by TargetScan. QRT-PCR and western blot were used to measure the relative expression levels of circNFIX, miR-34a-5p and NOTCH and identify their correlation in glioma. RNA immunoprecipitation (RIP) validated the binding relationship between circNFIX and miR-34a-5p, while the targeted relationship between NOTCH1 and miR-34a-5p was verified by a dual luciferase reporter assay. Cell viability and mobility were examined by a CCK-8 assay and wound healing assay, and a flow cytometry assay was employed to analyze cell apoptosis. The nude mouse transplantation tumor experiment verified that si-circNFIX exerted a suppressive effect on glioma progression in vivo.Results: Twelve circRNAs were differentially expressed between the tissue types. Of those, circNFIX was the sole circRNA to be overexpressed in glioma among the five methods of finding circRNAs. In addition, the Notch signaling pathway was considerably upregulated in tumor tissues compared with the paired normal brain tissues. It was determined that circNFIX acted as a sponge of miR-34a-5p, a miRNA that targeted NOTCH1. Downregulation of circNFIX and upregulation of miR-34a-5p both inhibited cell propagation and migration. Furthermore, a miR-34a-5p inhibitor neutralized the suppressive effect of si-circNFIX on glioma cells. Si-circNFIX and miR-34a-5p mimics promoted cell apoptosis. Moreover, it was demonstrated in vivo that si-circNFIX could suppress glioma growth by regulating miR-34a-5p and NOTCH1.Conclusion: CircNFIX was markedly upregulated in glioma cells. CircNFIX could regulate NOTCH1 and the Notch signaling pathway to promote glioma progression by sponging miR-34a-5p via the Notch signaling pathway. This finding provided a deeper insight into the function of circNFIX in human glioma cancer progression

Multiple organ infection and the pathogenesis of SARS

After >8,000 infections and >700 deaths worldwide, the pathogenesis of the new infectious disease, severe acute respiratory syndrome (SARS), remains poorly understood. We investigated 18 autopsies of patients who had suspected SARS; 8 cases were confirmed as SARS. We evaluated white blood cells from 22 confirmed SARS patients at various stages of the disease. T lymphocyte counts in 65 confirmed and 35 misdiagnosed SARS cases also were analyzed retrospectively. SARS viral particles and genomic sequence were detected in a large number of circulating lymphocytes, monocytes, and lymphoid tissues, as well as in the epithelial cells of the respiratory tract, the mucosa of the intestine, the epithelium of the renal distal tubules, the neurons of the brain, and macrophages in different organs. SARS virus seemed to be capable of infecting multiple cell types in several organs; immune cells and pulmonary epithelium were identified as the main sites of injury. A comprehensive theory of pathogenesis is proposed for SARS with immune and lung damage as key features

Sciences of the USA 1418 -1421 ͉ PNAS

The discovery of the block-like structure of linkage disequilibrium (LD) in human populations holds the promise of delineating the etiology of common diseases. However, understanding the magnitude, mechanism, and utility of between-population LD sharing is critical for future genome-wide association studies. In this study, substantial LD sharing between six non-African populations was observed, although much less between African-American and non-African, based on 20,000 SNPs of chromosome 21. We also demonstrated the respective roles of recombination and demographic events in shaping LD sharing. Furthermore, we showed that the haplotype-tagged SNPs chosen from one population are portable to the others in East Asia. Therefore, we concluded that the magnitude of LD sharing between human populations justifies the use of representative populations for selecting haplotypetagged SNPs in genome-wide association studies of complex diseases. bottleneck ͉ genetic distance ͉ association study ͉ common disease ͉ genetic variant C omprehensive testing of the association between genetic variations in the human genome and common diseases holds the promise of delineating the genetic architecture of these diseases (1-5). Substantial sharing of the boundaries and specific haplotypes of linkage disequilibrium (LD) blocks between populations was observed (6). However, variations of haplotype and LD across populations were also reported, raising concerns on its practical hindrance for genomewide testing of association (7-9). Conflicting observations on the magnitude of LD sharing between human populations, therefore, call for a careful examination of the following three questions, which are fundamental in developing strategies for genomewide testing of association. First, measurement of LD sharing between populations should be made independent of the definition of LD blocks, which introduce inconsistent block boundaries (10). Second, the mechanisms that shape LD sharing between populations are yet to be fully explored although the roles of recombination hotspots and demographic events have been implicated To address the aforementioned questions, we typed Ͼ20,000 SNPs on chromosome 21 in seven populations: three representative continental populations [African-American (AFR), European (EUR), and Han Chinese (HAN)] and four other major East Asian (EA) populations. This design allows a close examination of LD sharing between continental groups as well as those within East Asia. In this report, we measured the LD sharing between populations independent of the definition of LD block; and we showed that bottleneck events play a critical role in shaping the LD sharing between Africans and nonAfricans, but much less so between non-Africans. An important question for applying HapMap results to disease studies is how tagSNPs selected from a HapMap population will be ported to disease studies performed in other populations. In this study, we showed that tagSNPs selected from representative continental populations are indeed portable to the others in the same continent for association studies, at least in East Asia, with reasonable efficiency. In addition, we proposed a simple guideline that allows a quick evaluation of the portability of tagSNPs between populations by typing a small number of SNPs. Results Overall 26,112 SNPs were selected and typed in this study, and the data from 19,060 SNPs passed the quality control criteria and were used for further analyses. The SNPs and quality control criteria for SNP selection are described in Materials and Methods. Seven world populations, including EUR, AFR, and five EA populations, were studied. The five EA populations, i.e., HAN, Miao (HMJ), Zhuang (CCY), Wa (WBM), and Uighur (UIG), represent five major linguistic families spoken in East Asia. Preservation of LD between populations, i.e., LD sharing (S, or S AB when the population A was given as reference), is measured by the proportion of SNP pairs in LD in one population (population A or the reference) that are also in LD in another (population B). In this study, LD sharing was estimated without invoking the inference of haplotype blocks; therefore, the measure is independent of the definition of haplotype blocks. LD between two loci was measured in r 2 (16). Detail for the measure of LD sharing is described in Materials and Methods. LD sharing between EAs ranges from 63-74% for r 2 Ն 0.1 and 70-84% for r 2 Ն 0.5 (se

Multivalent HA DNA Vaccination Protects against Highly Pathogenic H5N1 Avian Influenza Infection in Chickens and Mice

Sustained outbreaks of highly pathogenic avian influenza (HPAI) H5N1 in avian species increase the risk of reassortment and adaptation to humans. The ability to contain its spread in chickens would reduce this threat and help maintain the capacity for egg-based vaccine production. While vaccines offer the potential to control avian disease, a major concern of current vaccines is their potency and inability to protect against evolving avian influenza viruses.The ability of DNA vaccines encoding hemagglutinin (HA) proteins from different HPAI H5N1 serotypes was evaluated for its ability to elicit neutralizing antibodies and to protect against homologous and heterologous HPAI H5N1 strain challenge in mice and chickens after DNA immunization by needle and syringe or with a pressure injection device. These vaccines elicited antibodies that neutralized multiple strains of HPAI H5N1 when given in combinations containing up to 10 HAs. The response was dose-dependent, and breadth was determined by the choice of the influenza virus HA in the vaccine. Monovalent and trivalent HA vaccines were tested first in mice and conferred protection against lethal H5N1 A/Vietnam/1203/2004 challenge 68 weeks after vaccination. In chickens, protection was observed against heterologous strains of HPAI H5N1 after vaccination with a trivalent H5 serotype DNA vaccine with doses as low as 5 microg DNA given twice either by intramuscular needle injection or with a needle-free device.DNA vaccines offer a generic approach to influenza virus immunization applicable to multiple animal species. In addition, the ability to substitute plasmids encoding different strains enables rapid adaptation of the vaccine to newly evolving field isolates

Geostress effect on resistivity and its relevant correction method

For reservoirs with abnormally high pressure and high geostress, formation resistivity can be greatly affected. This increase of resistivity resulting from high stress causes errors in the identification of reservoir fluids. In order to investigate the effect of stress on resistivity, resistivity measurement was conducted simultaneously with triaxial testing to obtain rock resistivity under high temperature and high pressure. The changes of resistivity and resistivity increasing coefficient with horizontal differential stress and minimum horizontal stress were revealed from experiments. Besides, field data were analyzed to show the main influencing factors of formation resistivity under reservoir conditions. In addition, a new resistivity correction model for high geostress formation was derived in this work. The interpretation results are in good agreement with well testing data in the Keshen area of the Tarim oilfield, China

Weld defect classification in radiographic images using unified deep neural network with multi-level features

Deep neural network (DNN) exhibits state-of-the-art performance in many fields including weld defect classification. However, there is still a large room for improving the classification performance over the generic DNN models. In this paper, a unified deep neural network with multi-level features is proposed for weld defect classification. Firstly, we define 11 weld defect features as inputs of our proposed classification model. Not limited to geometric and intensity features, 4 features based on the intensity contrast between weld defect and its background are proposed in this paper. Secondly, we construct a novel deep learning framework: a unified deep neural network, where multi-level features of each hidden layer are fused by the last hidden layer to predict the type of weld defect comprehensively. In addition, we investigate pre-training and fine-turning strategies to get better generalization performance with small dataset. Comparing with other classification methods like SVM and generic DNN model, our framework takes full advantage of multi-level features extracted from each hidden layer, an outstanding performance is shown where the classification accuracy is improved by 3.18% and 4.33% on the test dataset, to reach 91.36%