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Neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) is an E3 ubiquitin ligase that has been reported to participate in multiple cellular procedures by regulating of substrate ubiquitination and subsequent protein degradation. A great amount of evidence has demonstrated that NEDD4L mainly functions as a tumor suppressor in most cancer types, while it also acts as an oncogene in a few cancers. In this review, we summarize the potential role of NEDD4L in carcinogenesis and the related underlying molecular mechanism to improve our understanding of its functions in the tumorigenesis of human malignancies. Developing clinical drugs targeting NEDD4L could be a potential therapeutic strategy for cancer therapy in the future.

Background: There have been no systemic studies about right heart filling pressure and right ventricular (RV) distensibility in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Therefore, we aimed to explore combinations of echocardiographic indices to assess the stages of RV diastolic dysfunction.Methods and Results: We recruited 32 healthy volunteers and 71 patients with CTEPH. All participants underwent echocardiography, cardiac catheterization (in patients with CTEPH), and a 6-min walk test (6MWT). The right atrial (RA) end-systolic area was adjusted for body surface area (BSA) (indexed RA area). RV global longitudinal diastolic strain rates (SRs) and RV ejection fraction (EF) were measured by speckle tracking and three-dimensional echocardiography (3D echo), respectively. All 71 patients with CTEPH underwent pulmonary endarterectomy. Of the 71 patients, 52 (73%) had decreased RV systolic function; 12 (16.9%), 26 (36.6%), and 33 (46.5%) patients had normal RV diastolic pattern, abnormal relaxation (stage 1), and pseudo-normal patterns (stage 2), respectively. The receiver operating characteristic curve analysis showed that the optimal cut-off values of early diastolic SR 8.8 cm2/BSA had the best accuracy in identifying patients with RV diastolic dysfunction, with 87% sensitivity and 82% specificity. During a mean follow-up of 25.2 months after pulmonary endarterectomy, the preoperative indexed RA area was shown as an independent risk factor of the decreased 6MWT distance.Conclusions: Measuring early diastolic SR and indexed RA area would be useful in stratifying RV diastolic function.

Ovarian cancer ranks as the fifth most common cause of cancer-related death in females. The molecular mechanisms of ovarian carcinogenesis need to be explored in order to identify effective clinical therapies for ovarian cancer. Recently, multi-omics approaches have been applied to determine the mechanisms of ovarian oncogenesis at genomics (DNA), transcriptomics (RNA), proteomics (proteins), and metabolomics (metabolites) levels. Multi-omics approaches can identify some diagnostic and prognostic biomarkers and therapeutic targets for ovarian cancer, and these molecular signatures are beneficial for clarifying the development and progression of ovarian cancer. Moreover, the discovery of molecular signatures and targeted therapy strategies could noticeably improve the prognosis of ovarian cancer patients.

Pepper is an important vegetable in the world. In this work, mRNA and ncRNA transcriptome profiles were applied to understand the heterosis effect on the alteration in the gene expression at the seedling and flowering stages between the hybrid and its parents in Capsicum chinense. Our phenotypic data indicated that the hybrid has dominance in leaf area, plant scope, plant height, and fruit-related traits. Kyoto Encyclopedia of Genes and Genomes analysis showed that nine members of the plant hormone signal transduction pathway were upregulated in the seedling and flowering stages of the hybrid, which was supported by weighted gene coexpression network analysis and that BC332_23046 (auxin response factor 8), BC332_18317 (auxin-responsive protein IAA20), BC332_13398 (ethylene-responsive transcription factor), and BC332_27606 (ethylene-responsive transcription factor WIN1) were candidate hub genes, suggesting the important potential role of the plant hormone signal transduction in pepper heterosis. Furthermore, some transcription factor families, including bHLH, MYB, and HSF were greatly over-dominant. We also identified 2,525 long ncRNAs (lncRNAs), 47 micro RNAs (miRNAs), and 71 circle RNAs (circRNAs) in the hybrid. In particular, downregulation of miR156, miR169, and miR369 in the hybrid suggested their relationship with pepper growth vigor. Moreover, we constructed some lncRNA–miRNA–mRNA regulatory networks that showed a multi-dimension to understand the ncRNA relationship with heterosis. These results will provide guidance for a better understanding of the molecular mechanism involved in pepper heterosis.

E-cadherin plays a pivotal role in cancer progression, including the epithelial-mesenchymal transition (EMT) process and tumor metastasis. Loss of E-cadherin contributes to enhanced invasion and metastasis in human cancers. Therefore, restoring E-cadherin could be a potential approach for cancer therapy. Multiple natural compounds have been shown to possess anti-tumor activities through the regulation of key molecules in signaling pathways, including E-cadherin. In this review, we describe the numerous compounds that restore the expression of E-cadherin in genital and urinary malignancies. We further discuss the potential anti-tumor molecular mechanisms of these agents as the activators of E-cadherin in genital and urinary cancers. Although these compounds exhibit their potential to inhibit the development and progression of cancers, there are several challenges to developing them as therapeutic drugs for cancer patients. Poor bioavailability in vivo is the main disadvantage of these compounds. Modification of compound structures has produced actual improvements in bioavailability. Nanoparticle-based delivery systems could be useful to deliver the agents to targeted organs. These compounds could be new promising therapeutic agents for the treatment of human genital and urinary cancers. Further investigations are required to determine the safety and side effects of natural compounds using animal models prior to clinical trials. Keywords: E-cadherin, EMT, invasion, cancer, natural agents, therapy

Abstract Emerging evidence shows that epithelial-mesenchymal transition (EMT) plays a crucial role in tumor invasion, metastasis, cancer stem cells, and drug resistance. Data obtained thus far have revealed that F-box proteins are critically involved in the regulation of the EMT process and stem cell differentiation in human cancers. In this review, we will briefly describe the role of EMT and stem cells in cell metastasis and drug resistance. We will also highlight how numerous F-box proteins govern the EMT process and stem cell survival by controlling their downstream targets. Additionally, we will discuss whether F-box proteins involved in drug resistance are associated with EMT and cancer stem cells. Targeting these F-box proteins might be a potential therapeutic strategy to reverse EMT and inhibit cancer stem cells and thus overcome drug resistance in human cancers.

The endosymbiotic Wolbachia bacteria frequently cause cytoplasmic incompatibility (CI) in their insect hosts, where Wolbachia-infected males cross with uninfected females, leading to no or fewer progenies, indicating a paternal modification by Wolbachia. Recent studies have identified a Wolbachia protein, CidB, containing a DUB (deubiquitylating enzyme) domain, which can be loaded into host sperm nuclei and involved in CI, though the DUB activity is not necessary for CI in Drosophila melanogaster. To investigate whether and how Wolbachia affect protein ubiquitination in testes of male hosts and are thus involved in male fertility, we compared the protein and ubiquitinated protein expressions in D. melanogaster testes with and without Wolbachia. A total of 643 differentially expressed proteins (DEPs) and 309 differentially expressed ubiquitinated proteins (DEUPs) were identified to have at least a 1.5-fold change with a p-value of Wolbachia. Four genes coding for DEUPs in ubiquitin proteasome pathways were knocked down, respectively, in Wolbachia-free fly testes. Among them, Rpn6 and Rpn7 knockdown caused male sterility, with no mature sperm in seminal vesicles. These results reveal deubiquitylating effects induced by Wolbachia infection, suggesting that Wolbachia can widely deubiquitinate proteins that have crucial functions in male fertility of their hosts, but are not involved in CI. Our data provide new insights into the regulatory mechanisms of endosymbiont/host interactions and male fertility.

Kinematically aligned total knee replacements have been shown to better restore physiological kinematics than mechanical alignment and also offer good postoperative satisfaction. The purpose of this study is to evaluate the extent to which an inclined joint line in a kinematically aligned knee can alter the postoperative kinematics. A multi-body dynamic simulation was used to identify kinematic changes in the joint. To accurately compare mechanical alignment, kinematic alignment and a natural knee, a “standard” patient with neutral alignment of the lower extremities was selected for modeling from a joint database. The arthroplasty models in this study were implanted with a single conventional cruciate-retaining prosthesis. Each model was subjected to a flexion movement and the anteroposterior translation of the femoral condyles was collected for kinematic analysis. The results showed that the mechanical alignment model underwent typical paradoxical anterior translation of the femoral condyles. Incorporating an inclined joint line in the model did not prevent the paradoxical anterior translation, but a 3° varus joint line in the kinematic alignment model could reduce the peak value of this motion by about 1 mm. Moreover, the inclined joint line did not restore the motion curve back to within the range of the kinematic curve of the natural knee. The results of this study suggest that an inclined joint line, as in the kinematic alignment model, can slightly suppress paradoxical anterior translation of the femoral condyles, but cannot restore kinematic motions similar to the physiological knee. This finding implies that prostheses intended to be used for kinematic alignment should be designed to optimize knee kinematics with the intention of restoring a physiological motion curve.

With the rapid development of science and technology, social competition becomes more and more fierce, and work pressure becomes more and more intense. The problem of sleep has become a disease of modern civilization, and in order to alleviate sleep problems and improve sleep quality, related research methods are constantly updated, and there are more and more ways to address these problems. In this paper, we propose a dynamic assisted sleep light that adjusts the color temperature, illuminance, and frequency of change by controlling the backlight of the smart mobile device, so that the user experiences an improved quality of sleep. In this study, the methods of subjective questionnaire survey and non-subjective physiological parameter measurement were adopted for analysis. The results showed that the continuous use of the light source could continuously enhance the user’s delta energy during sleep and promote the improvement of sleep quality.

Background: Emerging evidence has demonstrated that SPOP functions as an oncoprotein in kidney cancer to promote tumorigenesis by ubiquitination-mediated degradation of multiple regulators of cellular proliferation and apoptosis. However, the detailed molecular mechanism underlying the oncogenic role of SPOP in kidney tumorigenesis remains elusive. Methods: Multiple approaches such as Co-IP, Transfection, RT-PCR, Western blotting, and animal studies were utilized to explore the role of SPOP in kidney cancer. Findings: Here we identified LATS1, a critical component of the Hippo tumour suppressor pathway, as a novel ubiquitin substrate of SPOP. We found that LATS1 interacted with Cullin3, and depletion of Cullin 3 upregulated the abundance of LATS1 largely via prolonging LATS1 protein half-life. Mechanistically, SPOP specifically interacted with LATS1, and promoted the poly-ubiquitination and subsequent degradation of LATS1 in a degron-dependent manner. As such, over-expression of SPOP promoted cell proliferation partly through regulating cell cycle distribution in kidney cancer cells. Furthermore, SPOP also promoted kidney cancer cell invasion via degrading LATS1. Interpretation: Our study provides evidence for a novel mechanism of SPOP in kidney cancer progression in part through promoting degradation of the LATS1 tumour suppressor.

Objectives. To observe the effect of avβ3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. Background. Percutaneous transluminal coronary angioplasty (PTCA) is currently the preferred method for the treatment of coronary heart disease. However, vascular restenosis still occurs after PTCA treatment, severely affecting the clinical efficacy of PTCA. Integrin avβ3, which is widely expressed on various cell surfaces, plays an important role in the proliferation and migration of VSMCs. Methods. In this experiment, we used systematic evolution of ligands by exponential enrichment (SELEX) to screen out avβ3 ssDNA, which has high affinity and specificity to the avβ3 protein. MTT, Transwell, and cell scratch assays were carried out to examine the effect of avβ3 ssDNA on the proliferation and migration of VSMCs. Flow cytometry was performed to detect apoptosis and cell cycle progression. The effect of avβ3 ssDNA on the Ras-phosphatidylinositol-4,5-bisphosphate 3-kinase/mitogen-activated protein kinase (PI3K/MAPK) signaling pathway was evaluated by quantitative reverse transcription polymerase chain reaction and western blot. Results. In the present study, we found that avβ3 ssDNA significantly decreased the expression of osteopontin, focal adhesion kinase, Ras, p-PI3K, and p-MAPK at both mRNA and protein levels (P

This paper focuses on the dynamic response of three asymmetric and nonlinear packaging systems (ANPSs) of practical transport package under random excitation. Next to presenting the displacement probability density functions (PDFs) of ANPSs derived through FPK equations, the influences of the excitation grades and the characteristic parameters (such as the damping, the nonlinear stiffness, and the strain) of packaging cushion materials on the response are discussed in detail. Then, the generalized PDFs of the response peaks are defined and examined by three common distributions. The investigation shows that “inverse excitation cushion factors” (IECFs) have a significance on effecting the displacement PDFs approaching different distributions. Most PDFs of the unilateral response peaks approach Rayleigh distributions and present non-Gaussian characters. The present methods are verified through the validation numerical solutions. Furthermore, the application of the scheme for fatigue damage evaluation of the transport package is carried out.

It has been conjectured that gravity may emerge from an entropic force arising on a holographic screen due to its purportedly intrinsic thermodynamic properties. Here, the authors test this conjecture by demonstrating that this key assumption of entropic force is inconsistent with general relativity.

Aluminum matrix composites reinforced with SiC particles (SiC p ) were prepared by electromagnetic stirring. This article aims to study the effects of SiC p addition on microstructure and mechanical properties of SiC p /ZL105, finally leading to expended range for ZL105 alloy application. Microstructural studies were carried out by optical microscope, scanning electron microscopy, and energy dispersive spectrometer. Tensile and hardness tests were conducted in order to identify mechanical properties. It was found that addition of 1.5 wt% SiC p causes the refined microstructure (including primary α-Al and eutectic Si) and reduced secondary dendrite arm spacing of α-Al matrix (12.6 μm). Compared to the ZL105 alloy, the ultimate tensile strength, elongation, and hardness of the composite with 1.5 wt% SiC p were increased by 24.6%, 37.3%, and 27.0%, respectively. The improved mechanical properties can mainly be attributed to the refinement of primary α-Al and eutectic Si, and uniformed dispersion of SiC p . Furthermore, the effects of voltage and agitation frequency of magnetic field on microstructure of composites were discussed.

The microstructure and hardness of rheo-forming AZ91-Y alloy before and after solution treatment (ST) have been investigated by means of optical microscope (OM), scanning electron microscope (SEM) equipped with energy dispersive spectroscopy (EDS), X-ray diffraction (XRD) and Vickers. The experimental results showed that the β-Mg17Al12 phase of alloy was nearly dissolved after ST for 5 min. With the increasing of ST duration to 28 h, both the primary and secondarily solidified α-Mg grains faded away. At the same time, the alloy exhibited a much smoother surface due to the diffusion of solute atoms (Al). During ST, the thermal stable phase of Al2Y produced by ultrasonic vibration retained its size and morphology. As the ST duration was increased, the alloy hardness decreased sharply at first, and then gradually reached a minimum level. The alloy’s appropriate ST duration at 410 °C was approximately 28 h.

In this paper, the effect of heat treatment (solution treatment and artificial aging) on the microstructure and properties of as-cast Al5Si1Cu0.5Mg aluminum alloy and its composite reinforced with 1.5 wt.% SiC particles was studied. The results showed that at 520 °C the optimal solution time for the aluminum alloy and its composite is 9 h and 6 h, respectively. After solution treatment, the microstructure of these two materials consists of a uniform distribution of nearly spherical eutectic Si and skeletal γ phase, furthermore, the composite eutectic Si phase is smaller and γ phase is more dispersed. After artificial aging at 175 °C for 6 h, the microstructure of the composite is more dispersed and finer than that of the aluminum alloy on the whole and Al2Cu is precipitated. After heat treatment, the microhardness, ultimate tensile strength, and elongation of the aluminum alloy and its composite are higher than those of the as-casts. At the same time, the morphology of tensile fracture surface changes very much from a large area of cleavage plane to a large number of dimples and the tearing ridges become thicker for both the aluminum alloy and its composite.

In this study, we demonstrate a novel H2O2 activatable photosensitizer (compound 7) which contains a diiodo distyryl boron dipyrromethene (BODIPY) core and an arylboronate group that quenches the excited state of the BODIPY dye by photoinduced electron transfer (PET). The BODIPY-based photosensitizer is highly soluble and remains nonaggregated in dimethyl sulfoxide (DMSO) as shown by the intense and sharp Q-band absorption (707 nm). As expected, compound 7 exhibits negligible fluorescence emission and singlet oxygen generation efficiency. However, upon interaction with H2O2, both the fluorescence emission and singlet oxygen production of the photosensitizer can be restored in phosphate buffered saline (PBS) solution and PBS buffer solution containing 20% DMSO as a result of the cleavage of the arylboronate group. Due to the higher concentration of H2O2 in cancer cells, compound 7 even with low concentration is particularly sensitive to human cervical carcinoma (HeLa) cells (IC50 = 0.95 μM) but hardly damage human embryonic lung fibroblast (HELF) cells. The results above suggest that this novel BODIPY derivative is a promising candidate for fluorescence imaging-guided photodynamic cancer therapy.

Microstickies in whitewater have caused serious deterioration of paper quality and low efficiency of paper machine runnability. To solve this problem it is necessary to master the characteristics of various aspects of microstickies. In this study, the physicochemical properties and size distribution of microstickies in whitewater of three typical kinds of waste papers, old newspaper (ONP), old book paper (OBP), and mixed office wastepaper (MOW), were investigated by conventional methods and a modified Flow Cytometry Method (FCM). The results showed that white water microstickies in different kinds of waste paper have different characteristics. This is a premise for analyzing stickies problems. Furthermore, in a certain kind of waste paper, the physicochemical properties and the direct determination of size and number of microstickies particle in whitewater can be combined together and taken as a whole to account for more phenomena or deduce more mechanisms, such as agglomeration and deposition, etc.

Ethyl levulinate (EL) can be produced from bio-based levulinic acid (LA) and ethanol. Experimental investigations were conducted to evaluate and compare the performances and exhaust emission levels of ethyl levulinate as an additive to conventional diesel fuel, with EL percentages of 5%, 10%, 15% (with 2% n-butanol), and 20% (with 5% n-butanol), in a horizontal single-cylinder four stroke diesel engine. Brake-specific fuel consumptions of the EL-diesel blends were about 10% higher than for pure diesel because of the lower heating value of EL. NOx and CO2 emissions increased with engine power with greater fuel injections, but varied with changing EL content of the blends. CO emissions were similar for all of the fuel formulations. Smoke emissions decreased with increasing EL content.

Henan is the main agricultural province in China and is the top producer of wheat, representing 25% of the national wheat output. Henan has been the top province in terms of total food crop production since 2000. So, agricultural residue resources, which could provide material for future social and economic development, are abundant in Henan. But the province is facing critical problems from burning agricultural residues. Both efficient use and environmental protection of the resources are beginning to receive more attention. This study assessed the agricultural residue resources available for utilization and examined recent development targets in Henan. Agricultural residues were estimated for the base year 2009. Approximately 59.12 million tonnes of agricultural residues were consumed in various ways, and the average percentage of agricultural residue utilization was 70.07%. Agricultural residue is mainly used as a fertilizer, an energy source, industrial material, forage, and as feedstock for edible fungi. Short-term targets were provided for the development of suitable uses for agricultural residues through several demonstration projects, which will help to increase the efficient use of agricultural residue in Henan, China.

To evaluate the shock characteristics of critical component for a nonlinear packaging system, a new concept of three-dimensional shock spectrum was proposed. Three key coordinate parameters, such as the nondimensional pulse duration, the frequency parameter ratio and the ratio of the maximum response acceleration to the peak pulse acceleration, were governed in a novel dynamical mathematical model. It is shown that the shock response of critical component is weakened owning to the decrease in the defined system parameter. Furthermore, at low frequency parameter ratio, the enhancement of the damping ratio of the critical component leads to the decrease in the peak of the shock response, which can also be reduced by the increase in damping ratio of cushioning pad at both lower and higher frequency parameter ratios. The discussion and analysis provide some insights into the design of cushioning packaging as well.

Cu_{x}Bi_{2}Se_{3} hosts both topological surface states and bulk superconductivity. It has been identified recently as a topological superconductor (TSC) with an extraordinary nematic, i.e., C_{2}-symmetric superconducting state and odd-parity pairing. Here, using scanning tunneling microscopy, we directly examine the response of the superconductivity of Cu_{x}Bi_{2}Se_{3} to magnetic field. Under out-of-plane fields (B_{⊥}), we discover elongated magnetic vortices hosting zero-bias conductance peaks consistent with the Majorana bound states expected in a TSC. Under in-plane fields (B_{//}), the average superconducting gap exhibits twofold symmetry with field orientation; the long C_{2} symmetry axes are pinned to the dihedral mirror planes under B_{//}=0.5 T but rotate slightly under B_{//}=1.0 T. Moreover, a nodeless Δ_{4x} gap structure is semiquantitatively determined for the first time. Our data paint a microscopic picture of the nematic superconductivity in Cu_{x}Bi_{2}Se_{3} and pose strong constraints on theory.

This paper investigated the influence of heat treatment (T6) on the dry sliding wear behavior of SiCp/Al-5Si-1Cu-0.5Mg composite that was fabricated by electromagnetic stirring method. The wear rates and friction coefficients were measured using a pin-on-disc tribometer under loads of 15–90 N at dry sliding speeds of 100 r/min, 200 r/min, and 300 r/min, over a sliding time of 15 min. The worn surfaces and debris were examined using a scanning electron microscope and was analyzed with an energy dispersive spectrometer. The experimental results revealed that SiCp/Al-5Si-1Cu-0.5Mg alloy treated with T6 exhibited lower wear rate and friction coefficient than the other investigated alloys. As the applied load increased, the wear rate and friction coefficient increased. While, the wear rate and friction coefficient decreased with the sliding speed increasing. The morphology of the eutectic silicon was spheroidal after the T6 heat treatment. SiCp particles and Al2Cu phase can be considered as the main raisons for improving the wear behavior. Abrasion and oxidation were the wear mechanisms at low load levels. However, the wear mechanisms at high load levels were plastic deformation and delamination.

Quaternary climatic factors have played a significant role in population divergence and demography. Here we investigated the phylogeography of Osteomeles schwerinae, a dominant riparian plant species of the hot/warm-dry river valleys of the Hengduan Mountains (HDM), Qinling Mountains (QLM) and Yunnan-Guizhou Plateau (YGP). Three chloroplast DNA (cpDNA) regions (trnD-trnT, psbD-trnT, petL-psbE), one single copy nuclear gene (glyceraldehyde 3-phosphate dehydrogenase; G3pdh), and climatic data during the Last Interglacial (LIG; c. 120-140 ka), Last Glacial Maximum (LGM; c. 21 ka), and Current (c. 1950-2000) periods were used in this study. Six cpDNA haplotypes and 15 nuclear DNA (nDNA) haplotypes were identified in the 40 populations of O. schwerinae. Spatial Analysis of Molecular Variance, median-joining networks, and Bayesian phylogenetic trees based on the cpDNA and nDNA datasets, all suggested population divergence between the QLM and HDM-YGP regions. Our climatic analysis identified significant heterogeneity of the climatic factors in the QLM and HDM-YGP regions during the aforementioned three periods. The divergence times based on cpDNA and nDNA haplotypes were estimated to be 466.4-159.4 ka and 315.8-160.3 ka, respectively, which coincide with the time of the weakening of the Asian monsoons in these regions. In addition, unimodal pairwise mismatch distribution curves, expansion times, and Ecological Niche Modeling suggested a history of population expansion (rather than contraction) during the last glaciation. Interestingly, the expansion times were found being well consistent with the intensification of the Asian monsoons during this period. We inferred that the divergence between the two main lineages is probably caused by disruption of more continuous distribution because of weakening of monsoons/less precipitation, whilst subsequent intensification of the Asian monsoons during the last glaciation facilitated the expansion of O. schwerinae populations.

Pancreatic cancer is one of the most aggressive human tumors in the United States. Curcumin, a polyphenol derived from the Curcuma longa plant, has been reported to exert its antitumor activity in pancreatic cancer. However, the molecular mechanisms of curcumin-mediated tumor suppressive function have not been fully elucidated. In the current study, we explore whether curcumin exhibits its anti-cancer function through inhibition of oncoprotein cell division cycle 20 (Cdc20) in pancreatic cancer cells. We found that curcumin inhibited cell growth, enhanced apoptosis, induced cell cycle arrest and retarded cell invasion in pancreatic cancer cells. Moreover, we observed that curcumin significantly inhibited the expression of Cdc20 in pancreatic cancer cells. Furthermore, our results demonstrated that overexpression of Cdc20 enhanced cell proliferation and invasion, and abrogated the cytotoxic effects induced by curcumin in pancreatic cancer cells. Consistently, downregulation of Cdc20 promoted curcumin-mediated anti-tumor activity. Therefore, our findings indicated that inhibition of Cdc20 by curcumin could be useful for the treatment of pancreatic cancer patients.

Synovial fibroblasts (SF) play a central role in the inflammatory and destructive process in rheumatoid arthritis (RA). High-mobility group box chromosomal protein 1 (HMGB1) or lipopolysaccharide (LPS) alone failed to induce significant changes in proliferation of cultured SF from RA patients, but premixed HMGB1 with LPS (HMGB1-LPS) significantly facilitated SF proliferation. HMGB1 alone failed to induce IL-6, MMP-3, and MMP-13 production in cultured SF but greatly enhanced LPS-induced expression of IL-6, MMP-3, and MMP-13 at both mRNA and protein levels. HMGB1-LPS synergistically upregulated TLR4 and receptor for advanced glycation endproducts (RAGE) expression on the surface of SF. Both blockers of TLR4 and RAGE significantly inhibited the synergistic effects of HMGB1-LPS on the production of IL-6 and MMPs, but blocking antibodies to TLR2 failed. HMGB1-LPS synergistically increased intracellular levels of phosphorylated p38 and phosphorylated IκB. Furthermore, both NF-κB inhibitor Bay11-7085 and p38 inhibitor SB203580 significantly suppressed the enhanced production of IL-6 and MMPs induced by HMGB1-LPS. In conclusion, HMGB1 acts in synergy with LPS to upregulate TLR4 and RAGE expression on the surface of SF in RA and then to augment IL-6, MMP-3, and MMP-13 production, which depends on p38 MAPK and NF-κB activation.

In the title compound, C8H6N4O3S, the dihedral angle between the pyrazine rings is 85.04 (1)°. In the crystal, molecules are arranged along the a axis and are linked by C—H...N hydrogen bonds and pyrazine–pyrazine π–π interactions [centroid–centroid distance = 3.800 (1) Å, forming an infinite chain array. The chains are connected by C—H...O(oxide) hydrogen bonds into layers lying parallel to the ab plane. Along the c axis, the layers are stacked and linked through C—H...O(sulfonyl) interactions, forming a three-dimensional network.

In the title complex, {[Cd(CH3COO)2(C11H8N2O)(H2O)]·2H2O}n, the CdII ion adopts an O5N2 pentagonal–bipyramidal coordination geometry with four acetate O atoms and one water O atom at the equatorial sites and two pyridine N atoms at the axial sites. The (pyridin-3-yl)(pyridin-4-yl)methanone ligand acts in a μ2-bridging mode, linking the metal atoms, leading to an infinite chain along [-110]. O—H...O hydrogen bonds involving the lattice water molecules connect these chains into a three-dimensional network.

In the title molecular salt, C11H10N2O2+·2ClO4−, the complete cation is generated by crystallographic twofold symmetry. The dihedral angle between the pyridyl rings is 67.07 (7)°. The crystal structure features N—H...Cl hydrogen bonds, forming sheets in the ab plane.

In the mononuclear title complex, [Ag(C10H6N4)2]ClO4, the AgI ion is surrounded by two 5-(pyridin-2-yl)pyrazine-2-carbonitrile ligands, forming a considerably distorted square-planar N4-coordination geometry, with two short and two long Ag—N distances. Each perchlorate anion links two mononuclear coordination units through C—H...O(perchlorate) hydrogen bonding, forming an infinite tape structure along [110]. Intermolecular π–π stacking interactions between adjacent pyridine and pyrazine rings [centroid–centroid distances of 3.777 (3) and 3.879 (2) Å] further assemble the tape motifs into a three-dimensional supramolecular structure.

In the mononuclear title complex, [Pt(CH3)Cl(C25H23N2P)], the N-benzyl-N-(diphenylphosphanylmethyl)pyridin-2-amine functions as a bidentate ligand with the pyridyl N atom and the phosphine P atom chelating the PtII ion, forming a six-membered metallocycle. The PtII atom adopts a square-planar coordination geometry with one methyl group and one chloride ligand bonding to the metal center in a cis relationship. C—H...π and C—H...Cl interactions help to consolidate the packing.

In the mononuclear title complex, [Pt(C7H7)2(C8H12)], the PtII ion exhibits a square-planar coordination geometry defined by two methylphenyl ligands and the mid-points of the two π-coordinated double bonds of cycloocta-1,5-diene. The two methylphenyl groups have a cis relationship with a C—Pt—C bond angle of 88.54 (18)° and a dihedral angle between the mean planes of the benzene rings of 83.87 (1)°. Each complex molecule links to four symmetry-related ones through intermolecular C—H...π interactions, forming a layer almost parallel to the bc plane.

Transplantation of olfactory ensheathing cells (OECs) has emerged as a very promising therapy for spinal cord injury (SCI). Also, local delivery of NT-3 can counteract pathological events and induce a regenerative response after SCI. Supplement of exogenetic NT-3 might be a new approach to SCI repair. In this study, we examined the therapeutic effect of rat NT-3 gene-modified OECs transplantation on SCI. Rat NT-3 gene was transfected into OECs using a retroviral system. The engineered NT-3-OECs were tested for their ability to express and secrete biologically active NT-3 in vitro. Then NT-3-OECs were implanted into contused T9 spinal cord of the adult rats. Their ability of survival and NT-3 production was examined. The effect of axon regeneration was evaluated at the morphological level and promotion of locomotor functional recovery were assessed. The result showed that genetically modified OECs were capable of surviving and producing NT-3 in vivo to significantly improve the recovery after SCI.

We study the global asymptotic stability of the equilibrium point for the fractional difference equation xn+1=(axn-lxn-k)/(α+bxn-s+cxn-t), n=0,1,…, where the initial conditions x-r,x-r+1,…,x1,x0 are arbitrary positive real numbers of the interval (0,α/2a),l,k,s,t are nonnegative integers, r=max⁡⁡{l,k,s,t} and α,a,b,c are positive constants. Moreover, some numerical simulations are given to illustrate our results.

Objective Methods Results Conclusion Lower limb discrepancy (LLD) was frequently observed in patients with idiopathic scoliosis (IS), potentially associated with etiopathogenesis. Although sole lifts had been proposed as a conservative treatment for IS, evidence supporting their efficacy was limited. This study aimed to assess the effects of sole lift intervention on pediatric patients with mild IS, specifically focusing on thoracolumbar/lumbar (TL/L) curvature.Twenty patients, with an average age of 12.3 ± 3.1 years and presenting mild TL/L curve (15.6° ± 6.2°), were selected from a pool of 267 pediatric IS patients in the outpatient of our spine center from February 2023 to August 2023. Inclusion criteria comprised a main TL/L curve ranging between 10° and 40°, the lower limb positioned at the convexity of the main curve, and LLD of less than 2 cm; individuals requiring bracing or surgical intervention were excluded. Custom sole lifts were used to address the shorter lower limb with the objective of leveling the pelvis. Radiographic evaluations were conducted both before and after intervention using standing full spine posteroanterior radiographs and full leg length radiographs. Statistical analysis was undertaken to evaluate curve correction and its associations with other influencing factors.The mean structural and functional LLD were 7.1 ± 4.5 mm and 7.1 ± 4.1 mm, respectively. Among the 20 patients, four exhibited structural LLD greater than 10 mm. The average follow‐up duration was 6.4 ± 1.9 months (range: 3–8 months). Following sole lift intervention (7.0 ± 3.0 mm), a significant reduction was observed in the TL/L curve compared to the pre‐sole lifting measurements (15.6° ± 6.2° vs. 12.1° ± 7.2°, p < 0.001), as well as a notable decrease in the thoracic curve (12.2° ± 4.0° vs. 8.6° ± 6.3°, p = 0.064). Nine patients experienced a significant curve reduction of ≥5°, while eight showed a reduction between 0° and 5°; however, two patients exhibited no change in curve magnitude. Furthermore, the correction rate of the TL/L curve correlated significantly with functional LLD (r = −0.484, p = 0.030) and pelvic obliquity (r = −0.556, p = 0.011), highlighting the active pelvic compensation in maintaining balance between the spine and lower limbs. Conversely, no significant correlation was observed between curve correction and structural LLD (p > 0.05). Additionally, even after adjusting for other influencing factors, the TL/L Cobb angle remained significantly different between pre‐ and post‐sole lifting (p = 0.037).This study confirmed the effectiveness of sole lift intervention in correcting TL/L and thoracic curves among the mild IS children with a main TL/L curve, providing a supplementary conservative treatment option for patients with the lower limb at the convexity of the main curve. Moreover, our findings underscored the active compensation of the lower limbs and the pelvis in the etiopathogenesis of IS, highlighting the importance of considering their influence in treatment strategies. [ABSTRACT FROM AUTHOR]

Background: The Malaysian government reacted to the pandemic’s economic effect with the Prihatin Rakyat Economic Stimulus Package (ESP) to cushion the novel coronavirus 2019 (COVID-19) impact on households. The ESP consists of cash assistance, utility discount, moratorium, Employee Provident Fund (EPF) cash withdrawals, credit guarantee scheme and wage subsidies. A survey carried out by the Department of Statistics Malaysia (DOSM) shows that households prefer different types of financial assistance. These preferences forge the need to effectively customise ESPs to manage the economic burden among low-income households. In this study, a recommender system for such ESPs was designed by leveraging data analytics and machine learning techniques. Methods: This study used a dataset from DOSM titled “Effects of COVID-19 on the Economy and Individual - Round 2,” collected from April 10 to April 24, 2020. Cross-Industry Standard Process for Data Mining was followed to develop machine learning models to classify ESP receivers according to their preferred subsidies types. Four machine learning techniques—Decision Tree, Gradient Boosted Tree, Random Forest and Naïve Bayes—were used to build the predictive models for each moratorium, utility discount and EPF and Private Remuneration Scheme (PRS) cash withdrawals subsidies. The best predictive model was selected based on F-score metrics. Results: Among the four machine learning techniques, Gradient Boosted Tree outperformed the rest. This technique predicted the following: moratorium preferences with 93.8% sensitivity, 82.1% precision and 87.6% F-score; utilities discount with 86% sensitivity, 82.1% precision and 84% F-score; and EPF and PRS with 83.6% sensitivity, 81.2% precision and 82.4% F-score. Households that prefer moratorium subsidies did not favour other financial aids except for cash assistance. Conclusion: Findings present machine learning models that can predict individual household preferences from ESP. These models can be used to design customised ESPs that can effectively manage the financial burden of low-income households.

Background: The Malaysian government reacted to the pandemic’s economic effect with the Prihatin Rakyat Economic Stimulus Package (ESP) to cushion the novel coronavirus 2019 (COVID-19) impact on households. The ESP consists of cash assistance, utility discount, moratorium, Employee Provident Fund (EPF) cash withdrawals, credit guarantee scheme and wage subsidies. A survey carried out by the Department of Statistics Malaysia (DOSM) shows that households prefer different types of financial assistance. These preferences forge the need to effectively customise ESPs to manage the economic burden among low-income households. In this study, a recommender system for such ESPs was designed by leveraging data analytics and machine learning techniques. Methods: This study used a dataset from DOSM titled “Effects of COVID-19 on the Economy and Individual - Round 2,” collected from April 10 to April 24, 2020. Cross-Industry Standard Process for Data Mining was followed to develop machine learning models to classify ESP receivers according to their preferred subsidies types. Four machine learning techniques—Decision Tree, Gradient Boosted Tree, Random Forest and Naïve Bayes—were used to build the predictive models for each moratorium, utility discount and EPF and Private Remuneration Scheme (PRS) cash withdrawals subsidies. The best predictive model was selected based on F-score metrics. Results: Among the four machine learning techniques, Gradient Boosted Tree outperformed the rest. This technique predicted the following: moratorium preferences with 93.8% sensitivity, 82.1% precision and 87.6% F-score; utilities discount with 86% sensitivity, 82.1% precision and 84% F-score; and EPF and PRS with 83.6% sensitivity, 81.2% precision and 82.4% F-score. Households that prefer moratorium subsidies did not favour other financial aids except for cash assistance. Conclusion: Findings present machine learning models that can predict individual household preferences from ESP. These models can be used to design customised ESPs that can effectively manage the financial burden of low-income households.