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This paper focused on the point-of-interest (POI) recommendation task. Recently, graph representation learning-based POI recommendation models have gained significant attention due to the powerful modeling capacity of graph structural data. Despite their effectiveness, we have found that recent methods struggle to effectively utilize information from POIs that have not been checked in, which could limit their performance. Hence, in this paper, we proposed a new model, named the multi-contextual graph contrastive learning (MCGCL) model, which introduces the contrastive learning into graph representation learning-based methods. First, MCGCL extracts interactions between POIs under different contextual factors from user check-in records using predefined graph structure information. Next, it samples important POI sets from different contextual factors using a random walk-based method. Then, it introduces a new contrastive learning loss that incorporates contextual information into traditional contrastive learning to enhance its ability to capture contextual information. Finally, MCGCL employs a graph neural network (GNN) model to learn representations of users and POIs. Extensive experiments on real-world datasets have demonstrated the effectiveness of MCGCL on the POI recommendation task compared to representative POI recommendation approaches.

Due to the majority of time people spent indoors, indoor air quality is not only critical to people's health, comfort, but can also significantly influence occupants perception on indoor environment. Air quality is closely related to many factors including thermal parameters, pollutant concentrations, and ventilation performance. However, the current building indoor air quality evaluation method is based the objective measurement of indoor parameters, without considering occupants’ subjective perception. This paper is aimed at summarizing a profound review on the PAQ evaluation method. Comparisons among various PAQ evaluating methods with advantages, similarities and differences were conducted. Analysis of literatures about indoor air quality in Chinese residential buildings field is also summarized, and discussion on the subjective influence of temperature and relative humidity, ventilation performance, volatile organic compounds (VOCs) concentration, and particulate matters on perceived air quality is carried out.

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Type 3 resistant starch from Canna edulis (Ce-RS3) is an insoluble dietary fiber which could improve blood lipids in animals, but clinically robust evidence is still lacking. We performed a double-blind randomized controlled trial to assess the effects of Ce-RS3 on lipids in mild hyperlipidemia. One hundred and fifteen patients were included followed the recruitment criteria, and were randomly allocated to receive Ce-RS3 or placebo (native starch from Canna edulis) for 12 weeks (20 g/day). In addition to serum lipids, complete blood counts, serum inflammatory factors, antioxidant indexes, and dietary survey, 16 S rRNA sequencing technique was utilized to analyze the gut microbiota alterations. Targeted quantitative metabolomics (TQM) was used to detect metabolite changes. Compared with the placebo, Ce- RS3 significantly decreased levels of total cholesterol, lowdensity lipoprotein cholesterol, and non-high-density lipoprotein cholesterol, and increased the glutathione peroxidase. Based on the 16 S rRNA sequencing, TQM, the correlation analysis, as well as the Kyoto Encyclopedia of Genes (KEGG) and Genomes and Human Metabolome Database (HMDB) analysis, we found that Ce-RS3 could increase the abundances of genera Faecalibacterium and Agathobacter, while reduce the abundances of genera norank_f_Ruminococcaceae and Christensenellaceae_R-7_ group to regulate phenylalanine metabolism, which could reduce the fatty acid biosynthesis and fatty acid elongation in the mitochondria to lower blood lipids. Conclusively, we firstly confirmed the feasibility of Ce-RS3 for clinical application, which presents a novel, effective therapy for the mild hyperlipidemia. (Chictr. org. cn. Clinical study on anti-mild hyperlipidemia of Canna edulis RS3 resistant starch, ID Number: ChiCTR2200062871).

IntroductionResistant starch (RS) has garnered attention for its health benefits, including modulating the gut microbiota and promoting the production of short-chain fatty acids (SCFAs).MethodsThis study investigates structural changes of type 3 resistant starch from Canna edulis (CE) during in vitro simulated digestion and explores its health-relevant properties using healthy individuals’ fecal microbiota.ResultsCE, prepared with a RS content of 59.38%, underwent a comprehensive analysis employing X-ray diffraction (XRD), fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). During simulated digestion, XRD analysis demonstrated a significant rise in CE’s relative crystallinity from 38.92 to 49.34%. SEM illustrated the transition of CE from a smooth to a rough surface, a notable morphological shift. Post-digestion, CE was introduced into microbial fermentation. Notably, propionic acid and valeric acid levels significantly increased compared to the control group. Furthere more, beneficial Bifidobacterium proliferated while pathogenic Escherichia-Shigella was suppressed. When comparing CE to the well-known functional food fructo-oligosaccharide (FOS), CE showed a specific ability to support the growth of Bifidobacterium and stimulate the production of short-chain fatty acids (SCFAs) without causing lactic acid accumulation.DiscussionCE demonstrates potential as a functional health food, with implications for gut health enhancement and SCFAs production.

Abstract Ailanthus altissima var. erythrocarpa is an A. altissima variety with high economic, ecological and ornamental value, but there have been no reports on the development of SSR primers for it. According to the SSR primer information provided by the transcriptome of A. altissima var. erythrocarpa, 120 individuals with different redness levels were used to screen polymorphic primers. Transcriptomic analysis revealed 10,681 SSR loci, of which mononucleotide repeats were dominant (58.3%), followed by dinucleotide and trinucleotide repeats (16.6%, 15.1%) and pentanucleotide repeats (0.2%). Among 140 pairs of randomly selected primers, nineteen pairs of core primers with high polymorphism were obtained. The average number of alleles (Na), average number of effective alleles (Ne), average Shannon’s diversity index (I), average observed heterozygosity (Ho), average expected heterozygosity (He), fixation index (F) and polymorphic information content (PIC) were 11.623, 4.098, 1.626, 0.516, 0.696, 0.232 and 0.671, respectively. Nineteen EST-SSR markers were used to study the genetic diversity and population structure of A. altissima var. erythrocarpa. The phylogenetic tree, PCoA, and structure analysis all divided the tested resources into two categories, clearly showing the genetic variation between individuals. The population showed high genetic diversity, mainly derived from intraspecific variation. Among nineteen pairs of primers, 4 pairs (p33, p15, p46, p92) could effectively distinguish and be used for fingerprinting of the tested materials. This study is of great significance for genetic diversity analysis and molecular-assisted breeding of A. altissima var. erythrocarpa.

Background: A diet high in purines can impair the function of the gut microbiota and disrupt purine metabolism, which is closely associated with the onset of hyperuricemia. Dietary regulation and intestinal health maintenance are key approaches for controlling uric acid (UA) levels. Investigating the impacts of fermented foods offers potential dietary interventions for managing hyperuricemia. Methods: In this study, we isolated a strain with potent UA-degrading capabilities from “Jiangshui”, a fermented food product from Gansu, China. We performed strain identification and assessed its probiotic potential. Hyperuricemic quails, induced by a high-purine diet, were used to assess the UA degradation capability of strain JS-3 by measuring UA levels in serum and feces. Additionally, the UA degradation pathways were elucidated through analyses of the gut microbiome and fecal metabolomics. Results: JS-3, identified as Lacticaseibacillus paracasei, was capable of eliminating 16.11% of uric acid (UA) within 72 h, rapidly proliferating and producing acid within 12 h, and surviving in the gastrointestinal tract. Using hyperuricemic quail models, we assessed JS-3’s UA degradation capacity. Two weeks after the administration of JS-3 (2 × 108 cfu/d per quail), serum uric acid (SUA) levels significantly decreased to normal levels, and renal damage in quails was markedly improved. Concurrently, feces from the JS-3 group demonstrated a significant degradation of UA, achieving up to 49% within 24 h. 16S rRNA sequencing revealed JS-3’s role in gut microbiota restoration by augmenting the probiotic community (Bifidobacterium, Bacteroides unclassified_f-Lachnospiraceae, and norank_fynorank_o-Clostridia_UCG-014) and diminishing the pathogenic bacteria (Macrococus and Lactococcus). Corresponding with the rise in short-chain fatty acid (SCFA)-producing bacteria, JS-3 significantly increased SCFA levels (p < 0.05, 0.01). Additionally, JS-3 ameliorated metabolic disturbances in hyperuricemic quails, influencing 26 abnormal metabolites predominantly linked to purine, tryptophan, and bile acid metabolism, thereby enhancing UA degradation and renal protection. Conclusions: For the first time, we isolated and identified an active probiotic strain, JS-3, from the “Jiangshui” in Gansu, used for the treatment of hyperuricemia. It modulates host–microbiome interactions, impacts the metabolome, enhances intestinal UA degradation, reduces levels of SUA and fecal UA, alleviates renal damage, and effectively treats hyperuricemia without causing gastrointestinal damage. In summary, JS-3 can serve as a probiotic with potential therapeutic value for the treatment of hyperuricemia.

The Carboniferous volcanic reservoirs in the Shixi area of the Junggar Basin are complex and diverse. Identifying the characteristics and main factors controlling high-quality volcanic reservoirs is the key to increasing oil and gas reserves and production in this area. Through core observations, thin section identification, physical property and pore structure analyses, combined with production data, the main controlling factors and development modes of high-quality reservoirs were analysed. The results show that the Carboniferous strata in the Shixi area mainly contain andesite and dacite of overflow facies, followed by volcanic breccia and tuff of explosive facies. Volcanic reservoirs in the study area are high-porosity–low-permeability and medium-porosity–low-permeability reservoirs. Volcanic breccia of explosive facies has the best physical properties, showing the characteristics of high porosity and medium permeability. The reservoir space is mainly composed of gas cavities, corrosion pores and fractures, among which the corrosion pores are the most important reservoir spaces of the Carboniferous volcanic rocks. Lithology and lithofacies, weathering and corrosion, and fractures are the main factors controlling the development of high-quality volcanic reservoirs. Volcanic rocks that had experienced weathering and denudation for a long time developed a large number of secondary corrosion pores due to the corrosion of soluble minerals or volcanic ash. Fractures further improved the physical properties, causing volcanic rocks to eventually develop into weathering crust reservoirs. The physical properties of the volcanic rocks far away from the weathering crust were improved through primary gas cavities and structural fractures, and these volcanic rocks eventually developed into the inner reservoir.

Graph convolutional networks (GCNs) are a promising approach for addressing the necessity for long-range information in hyperspectral image (HSI) classification. Researchers have attempted to develop classification methods that combine strong generalizations with effective classification. However, the current HSI classification methods based on GCN present two main challenges. First, they overlook the multi-view features inherent in HSIs, whereas multi-view information interacts with each other to facilitate classification tasks. Second, many algorithms perform a rudimentary fusion of extracted features, which can result in information redundancy and conflicts. To address these challenges and exploit the strengths of multiple features, this paper introduces an adaptive multi-feature fusion GCN (AMF-GCN) for HSI classification. Initially, the AMF-GCN algorithm extracts spectral and textural features from the HSIs and combines them to create fusion features. Subsequently, these three features are employed to construct separate images, which are then processed individually using multi-branch GCNs. The AMG-GCN aggregates node information and utilizes an attention-based feature fusion method to selectively incorporate valuable features. We evaluated the model on three widely used HSI datasets, i.e., Pavia University, Salinas, and Houston-2013, and achieved accuracies of 97.45%, 98.03%, and 93.02%, respectively. Extensive experimental results show that the classification performance of the AMF-GCN on benchmark HSI datasets is comparable to those of state-of-the-art methods.

Canna edulis Ker-Gawl is a versatile crop that integrates food, energy, and feed in China. The rhizome is a traditional Chinese medicine with a long history. However, there are few studies on chemical components. Crude plant extracts are a complex mixture of several biologically active secondary metabolites. Therefore, rapid and accurate identification and quantification are critical in phytochemical analysis. An efficient approach based on ultrahigh-performance liquid chromatography coupled with Q-Exactive Orbitrap tandem mass spectrometry (UHPLC Q-Exactive Orbitrap MS) was used to analyze the chemical components systematically. We used retention time, accurate molecular weight, parent peaks, fragment peaks, fragmentation characteristics, comparative analysis with the literature, reference standards, and standard databases, including ChemSpider, mzVault, MassBank, and mzCloud. A total of 54 chemical constituents were identified from the methanol extract of the rhizome, including 36 organic acids (with six phenolic acids), three phenols, one sugar (and its derivatives), one coumarin, one triterpenoid, ten N-containing organic compounds (including seven amino acids), and two other compounds. Moreover, three compounds were quantitatively analyzed and a methodological study of the three components was carried out. The established method provided satisfactory precision and accuracy, acceptable recovery, good linearity, and a reasonable detection limit. The UHPLC Q-Exactive Orbitrap MS method was used for the first time to accurately, quickly, and systematically characterize the compounds of the rhizome, revealing the pharmacodynamic substances and providing a theoretical basis for its quality control, in-depth research, and development.

Bicluster mining has been frequently studied in the data mining field. Because column constant biclusters (CCB) can be transformed to be discriminative rules, they have been widely applied in various fields. However, no research on incrementally mining CCB has been reported in the literature. In real situations, due to the limitation of computation resources (such as memory), it is impossible to mine biclusters from very large datasets. Therefore, in this study, we propose an incremental mining CCB method. CCB can be deemed as a special case of frequent pattern (FP). Currently the most frequently used method for incrementally mining frequent patterns is FP tree based method. In this study, we innovatively propose an incremental mining CCB method with modified FP tree data structure. The technical contributions lie in two aspects. The first aspect is that we propose a modified FP tree data structure, namely Feature Value Sorting Frequent Pattern (FVSFP) tree that can be easily maintained. The second aspect is that we innovatively design a method for mining CCB from FVSFP tree. To verify the performance of the proposed method, it is tested on several datasets. Experimental results demonstrated that the proposed method has good performance for incrementally handling a newly added dataset.

mTORC1 expression is increased during ageing of muscle, and on the other hand, its activation promotes muscle hypertrophy. Here, the authors assess whether mTORC1 has positive or negative effects on ageing, and show that its long-term inhibition preserves muscle mass and function and neuromuscular junction integrity, whereas muscle-specific activation is associated with sarcopenia.

Abstract Background Triple-negative breast cancer (TNBC) is a kind of malignant tumor with higher recurrence and metastasis rate. According to historical records, the dry rhizomes Cyperus rotundus L. could be ground into powder and mixed with ginger juice and wine for external application for breast cancer. We studied the effect of the ethanol extract of Cyperus rotundus L. (EECR) on TNBC cells and found its’ apoptosis-inducing effect with a dose-relationship. But the function mechanism of EECR on TNBC is still mysterious. Hence, the present research aimed to detect its function mechanism at the small molecule level through ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) metabolomics. Methods The CCK-8 assay and the Annexin V-FITC/PI assay were applied to test the effect of EECR on MDA-MB-231 cells and MDA-MB 468 cells at various concentrations of 0, 200, 400, and 600 μg/ml. UPLC-Q-TOF-MS/MS based metabolomics was used between the control group and the EECR treatment groups. Multivariate statistical analysis was used to visualize the apoptosis-inducing action of EECR and filtrate significantly changed metabolites. Results The apoptosis-inducing action was confirmed and forty-nine significantly changed metabolites (VIP > 1, p 1.2 or FC

Excitation-contraction coupling (ECC) is the process by which electrical excitation of muscle is converted into force generation. Depolarization of skeletal muscle resting potential contributes to failure of ECC in diseases such as periodic paralysis, intensive care unit acquired weakness and possibly fatigue of muscle during vigorous exercise. When extracellular K+ is raised to depolarize the resting potential, failure of ECC occurs suddenly, over a narrow range of resting potentials. Simultaneous imaging of Ca2+ transients and recording of action potentials (APs) demonstrated failure to generate Ca2+ transients when APs peaked at potentials more negative than –30mV. An AP property that closely correlated with failure of the Ca2+ transient was the integral of AP voltage with respect to time. Simultaneous recording of Ca2+ transients and APs with electrodes separated by 1.6mm revealed AP conduction fails when APs peak below –21mV. We hypothesize propagation of APs and generation of Ca2+ transients are governed by distinct AP properties: AP conduction is governed by AP peak, whereas Ca2+ release from the sarcoplasmic reticulum is governed by AP integral. The reason distinct AP properties may govern distinct steps of ECC is the kinetics of the ion channels involved. Na channels, which govern propagation, have rapid kinetics and are insensitive to AP width (and thus AP integral) whereas Ca2+ release is governed by gating charge movement of Cav1.1 channels, which have slower kinetics such that Ca2+ release is sensitive to AP integral. The quantitative relationships established between resting potential, AP properties, AP conduction and Ca2+ transients provide the foundation for future studies of failure of ECC induced by depolarization of the resting potential.

The performance of Chinese-named entity recognition (NER) has improved via word enhancement or new frameworks that incorporate various types of external data. However, for Chinese NER, syntactic composition (in sentence level) and inner regularity (in character-level) have rarely been studied. Chinese characters are highly sensitive to sentential syntactic data. The same Chinese character sequence can be decomposed into different combinations of words according to how they are used and placed in the context. In addition, the same type of entities usually have the same naming rules due to the specificity of the Chinese language structure. This paper presents a Kcr-FLAT to improve the performance of Chinese NER with enhanced semantic information. Specifically, we first extract different types of syntactic data, functionalize the syntactic information by a key-value memory network (KVMN), and fuse them by attention mechanism. Then the syntactic information and lexical information are integrated by a cross-transformer. Finally, we use an inner regularity perception module to capture the internal regularity of each entity for better entity type prediction. The experimental results show that with F1 scores as the evaluation index, the proposed model obtains 96.51%, 96.81%, and 70.12% accuracy rates on MSRA, resume, and Weibo datasets, respectively.

Miao is an important ethnic minority in China. Miao medicine (MM) is a pivotal of traditional Chinese medicine. It is an accumulation of the Miao people’s experience fighting against diseases for thousands of years and has been an important part of the Miao culture. The origin of MM is closely related to Miao culture, customs, and habits. MM gradually formed a traditional medical theoretical system with obvious regional characteristics, distinctive cultural characteristics, and unique efficacy. In this paper, we introduce and review the unique theoretical system of MM, including the basic theory of MM, the theory of medicine, nature, taste, and channel tropism, and the theory of entering the shelf. In addition, we summarize the development of MM to provide an overview of the theoretical characteristics and industrialisation of MM that is accessible to everyone.

With increasing air pollution, chronic bronchitis (CB) has become a major public health problem worldwide. Previous studies have shown beneficial effects of Bergenin (Ber) on chronic bronchitis. To facilitate understanding of the pathogenesis underlying CB as well as to elucidate the Ber therapeutic mechanism, it is crucial to confirm the rational biomarkers of CB and its treatment. This study aimed to investigate the preventive chronic bronchitis mechanism of Ber by applying a serum metabolomics strategy. In this study, 18 Sprague-Dawley rats were randomly divided into three groups,with six rats in each group. Rats from the CB and Ber groups were exposed to tobacco smoke for 1 hd−1 (1 h per day) for 28 days. Ber was administered orally to Ber rats 3 h after exposure every day, and the others were administered water. According to the morphometric analysis of the airway epithelium and the count of white blood cells in the bronchoalveolar lavage fluid, Ber suppressed the infiltration of inflammatory cells, inhibited the secretion of mucus, and reduced white blood cells in bronchoalveolar lavage fluid. The metabolic profiles of sera were analyzed by multivariate statistical analyses, including PCA, PLS-DA and OPLS-DA models, and revealed that the levels of thirteen metabolites were significantly changed and identified as potential biomarkers in the CB group and Ber group. The results suggested that the therapeutic mechanism of Ber may be related to the regulation of dysfunctions in glycerophospholipid, tryptophan, arginine and proline metabolism induced by CB, and changes in arachidonic acid metabolism.

As a severe metabolic disease, type 2 diabetes mellitus (T2DM) has aroused increasing public attentions. Resistant starch 3 (RS3), as a starch resistant to enzymatic hydrolysis owing to its special structure, has a good effect on improving insulin resistance and reducing blood sugar in T2DM patients. However, the possible mechanisms were barely interpreted yet. In our research, we aimed to evaluate the effects and the possible mechanisms of RS3 on the treatment of T2DM. ICR mice treated with high-fat diet (HFD) for eight weeks, and then injected with streptozotocin (STZ) (100 mg/kg) to establish the T2DM. We choose the mice with the fast blood glucose (FBG) more than 11 mmol/L as T2DM. After treated for 11 weeks the relevant data was analyzed. According to the results, the FBG was dramatically reduced (p

Abstract In this paper, we present an extended alternating proximal penalization algorithm for the modified multiple-sets feasibility problem. For this method, we first show that the sequences generated by the algorithm are summable, which guarantees that the distance between two adjacent iterates converges to zero, and then we establish the global convergence of the algorithm provided that the penalty parameter tends to zero.

Abstract In this paper, we present a family of conjugate gradient projection methods for solving large-scale nonlinear equations. At each iteration, it needs low storage and the subproblem can be easily solved. Compared with the existing solution methods for solving the problem, its global convergence is established without the restriction of the Lipschitz continuity on the underlying mapping. Preliminary numerical results are reported to show the efficiency of the proposed method.

Background: Tibetan medicinal substances (TMS) has a complete theory that is based on five source doctrines. The theories of “Liuwei”, “Baxing”, “Shiqi Gongxiao”, and “Sanhuawei” constitute the prominent core components of the five source doctrines with significant Tibetan characteristics. Objective: This review summarizes the existing literature on the metabolomics and its use in TMS and offers recommendations for future research. Methods: Studies on TMS and the application of metabolomics on TMS are reviewed and summarized. The shortcomings of existing studies and recommendations for future studies are discussed. Conclusions: The recent researches have studied on the theory of TMS. Metabolomics will be increasingly applied to the identification of compounds in TMS, and the resultant detection of biomarkers will help elucidate the metabolic pathways of these substances.

The aim of this paper was to seek an efficient method to preparative separation of alkaloid compounds from Aconitum coreanum (Guanbaifu), a well-known traditional Chinese medicinal plant for heart disease. Seven alkaloid compounds were successfully purified by pH-zone-refining counter-current chromatography with two-phase solvent system of petroleum ether–ethyl acetate–methanol–water (5:5:1:9, v/v/v/v), 10 mM triethylamine in upper phase and 10 mM hydrochloric acid in lower phase. From 3.5 g of crude extract, 356 mg of Guanfu base I, 578 mg of Guanfu base A, 74 mg of atisine, 94 mg of Guanfu base F, 423 mg of Guanfu base G, 67 mg of Guanfu base R and 154 mg of Guanfu base P were obtained with the purity of 96.40%, 97.2%, 97.5%, 98.1%, 98.9%, 98.3% and 98.4%. Their chemical structures were identified by TOF-MS and 1H-NMR. This study indicated that pH-zone-refining counter-current chromatography was an efficient method for separating the kind of alkaloids with low absorbance values.

This study examined whether activity is a contributing factor to motor terminal degeneration in mice that overexpress the G93A mutation of the SOD1 enzyme found in humans with inherited motor neuron disease. Previously, we showed that overload of muscles accomplished by synergist denervation accelerated motor terminal degeneration in dogs with hereditary canine spinal muscular atrophy (HCSMA). In the present study, we found that SOD1 plantaris muscles overloaded for 2 months showed no differences of neuromuscular junction innervation status when compared with normally loaded, contralateral plantaris muscles. Complete elimination of motor terminal activity using blockade of sciatic nerve conduction with tetrodotoxin cuffs for 1 month also produced no change of plantaris innervation status. To assess possible effects of activity on motor terminal function, we examined the synaptic properties of SOD1 soleus neuromuscular junctions at a time when significant denervation of close synergists had occurred as a result of natural disease progression. When examined in glucose media, SOD1 soleus synaptic properties were similar to wildtype. When glycolysis was inhibited and ATP production limited to mitochondria, however, blocking of evoked synaptic transmission occurred and a large increase in the frequency of spontaneous mEPCs was observed. Similar effects were observed at neuromuscular junctions in muscle from dogs with inherited motor neuron disease (HCSMA), although significant defects of synaptic transmission exist at these neuromuscular junctions when examined in glucose media, as reported previously. These results suggest that glycolysis compensates for mitochondrial dysfunction at motor terminals of SOD1 mice and HCSMA dogs. This compensatory mechanism may help to support resting and activity-related metabolism in the presence of dysfunctional mitochondria and prolong the survival of SOD1 motor terminals.

One new monoterpene glycoside (1), one new phenyl glycoside (2), one new caffeoyl derivative (3), were isolated from Scindapsus officinalis (Roxb.) Schott., along with four known compounds (4–7). Structures of the isolated compounds were elucidated by extensive analysis of spectroscopic data, especially 2D NMR data and comparison with literatures. All isolates were evaluated for anti-inflammatory activity against nitric oxide (NO) production in vitro. Compounds 3 and 7 exhibited moderate inhibitory effects on NO production with IC50 values of 12.2 ± 0.8 and 18.9 ± 0.3 μM, respectively.

Spinal muscular atrophy is caused by loss of the SMN1 gene and retention of SMN2. The SMN2 copy number inversely correlates with phenotypic severity and is a modifier of disease outcome. The SMN2 gene essentially differs from SMN1 by a single nucleotide in exon 7 that modulates the incorporation of exon 7 into the final SMN transcript. The majority of the SMN2 transcripts lack exon 7 and this leads to a SMN protein that does not effectively oligomerize and is rapidly degraded. However the SMN2 gene does produce some full-length SMN and the SMN2 copy number along with how much full-length SMN the SMN2 gene makes correlates with severity of the SMA phenotype. However there are a number of discordant SMA siblings that have identical haplotypes and SMN2 copy number yet one has a milder form of SMA. It has been suggested that Plastin3 (PLS3) acts as a sex specific phenotypic modifier where increased expression of PLS3 modifies the SMA phenotype in females. To test the effect of PLS3 overexpression we have over expressed full-length PLS3 in SMA mice. To ensure no disruption of functionality or post-translational processing of PLS3 we did not place a tag on the protein. PLS3 protein was expressed under the Prion promoter as we have shown previously that SMN expression under this promoter can rescue SMA mice. High levels of PLS3 mRNA were expressed in motor neurons along with an increased level of PLS3 protein in total spinal cord, yet there was no significant beneficial effect on the phenotype of SMA mice. Specifically, neither survival nor the fundamental electrophysiological aspects of the neuromuscular junction were improved upon overexpression of PLS3 in neurons.

An extension of subgradient method for solving variational inequality problems is presented. A new iterative process, which relates to the fixed point of a nonexpansive mapping and the current iterative point, is generated. A weak convergence theorem is obtained for three sequences generated by the iterative process under some mild conditions.