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Abstract Optimizing thermoelectric conversion efficiency requires the compromise of electrical and thermal properties of materials, which are hard to simultaneously improve due to the strong coupling of carrier and phonon transport. Herein, a one-pot approach realizing simultaneous second phase and Cu vacancies modulation is proposed, which is effective in synergistically optimizing thermoelectric performance in copper sulfides. Multiple lattice defects, including nanoprecipitates, dislocations, and nanopores are produced by adding a refined ratio of Sn and Se. Phonon transport is significantly suppressed by multiple mechanisms. An ultralow lattice thermal conductivity is therefore obtained. Furthermore, extra Se is added in the copper sulfide for optimizing electrical transport properties by inducing generating Cu vacancies. Ultimately, an excellent figure of merit of ~1.6 at 873 K is realized in the Cu1.992SSe0.016(Cu2SnSe4)0.004 bulk sample. The simple strategy of inducing compositional and structural modulation for improving thermoelectric parameters promotes low-cost high-performance copper sulfides as alternatives in thermoelectric applications.

Tyrosine kinase inhibitors (TKIs) have emerged as the first-line small molecule drugs in many cancer therapies, exerting their effects by impeding aberrant cell growth and proliferation through the modulation of tyrosine kinase-mediated signaling pathways. However, there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites, which may render patients with compromised immune function susceptible to diverse infections despite receiving theoretically efficacious anticancer treatments, alongside other potential side effects or adverse reactions. Therefore, an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods, clinical pharmacokinetics, and therapeutic drug monitoring of different TKIs. This paper provides a comprehensive overview of the advancements in pretreatment methods, such as protein precipitation (PPT), liquid-liquid extraction (LLE), solid-phase extraction (SPE), micro-SPE (μ-SPE), magnetic SPE (MSPE), and vortex-assisted dispersive SPE (VA-DSPE) achieved since 2017. It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography (HPLC) and high-resolution mass spectrometry (HRMS) methods, capillary electrophoresis (CE), gas chromatography (GC), supercritical fluid chromatography (SFC) procedures, surface plasmon resonance (SPR) assays as well as novel nanoprobes-based biosensing techniques. In addition, a comparison is made between the advantages and disadvantages of different approaches while presenting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

Abstract Normal high-density lipoprotein (nHDL) can induce angiogenesis in healthy individuals. However, HDL from patients with coronary artery disease undergoes various modifications, becomes dysfunctional (dHDL), and loses its ability to promote angiogenesis. Here, we identified a long non-coding RNA, HDRACA, that is involved in the regulation of angiogenesis by HDL. In this study, we showed that nHDL downregulates the expression of HDRACA in endothelial cells by activating WW domain-containing E3 ubiquitin protein ligase 2, which catalyzes the ubiquitination and subsequent degradation of its transcription factor, Kruppel-like factor 5, via sphingosine 1-phosphate (S1P) receptor 1. In contrast, dHDL with lower levels of S1P than nHDL were much less effective in decreasing the expression of HDRACA. HDRACA was able to bind to Ras-interacting protein 1 (RAIN) to hinder the interaction between RAIN and vigilin, which led to an increase in the binding between the vigilin protein and proliferating cell nuclear antigen (PCNA) mRNA, resulting in a decrease in the expression of PCNA and inhibition of angiogenesis. The expression of human HDRACA in a hindlimb ischemia mouse model inhibited the recovery of angiogenesis. Taken together, these findings suggest that HDRACA is involved in the HDL regulation of angiogenesis, which nHDL inhibits the expression of HDRACA to induce angiogenesis, and that dHDL is much less effective in inhibiting HDRACA expression, which provides an explanation for the decreased ability of dHDL to stimulate angiogenesis.

Benzodiazepines (BDZs) are used in clinics for anxiolysis, anticonvulsants, sedative hypnosis, and muscle relaxation. They have high consumptions worldwide because of their easy availability and potential addiction. They are often used for suicide or criminal practices such as abduction and drug-facilitated sexual assault. The pharmacological effects of using small doses of BDZs and their detections from complex biological matrices are challenging. Efficient pretreatment methods followed by accurate and sensitive detections are necessary. Herein, pretreatment methods for the extraction, enrichment, and preconcentration of BDZs as well as the strategies for their screening, identification, and quantitation developed in the past five years have been reviewed. Moreover, recent advances in various methods are summarized. Characteristics and advantages of each method are encompassed. Future directions of the pretreatment and detection methods for BDZs are also reviewed.

The ground motion intensity measure is a key parameter affecting the accuracy of probabilistic seismic demand analysis (PSDA). This paper uses the incremental dynamic analysis (IDA) results of 12 three-dimensional reinforced concrete (RC) high-rise structures to explore the efficiency and sufficiency of a spectral acceleration Sa(T) intensity measure (IM) in a continuous period T (0–8 s). Subsequently, the effects of higher modes and period softening on the results are investigated. Controlling periods – that is, the lower and upper bounds of periods – across the spectrum are also examined in order to propose an optimal IM Sa,GM that considers the effects of higher modes and nonlinear softening on the seismic responses of three-dimensional high-rise buildings. Finally, the proposed optimal IM Sa,GM is compared to the widely used IM of spectral acceleration at the first-mode period Sa(T1) of the structure and the improved IM Sa¯, which considers the first n modes in the field, based on the criteria of efficiency, practicality, sufficiency, proficiency, and scaling robustness. The results indicate that the efficiency and sufficiency of the IM Sa(T) fluctuate with increasing periods T and are affected by higher modes and period softening. Furthermore, the proposed optimal IM Sa,GM exhibits a significant decrease in dispersion with respect to the structural response (efficiency) and scores higher on sufficiency, practicality, proficiency, and effectivity robustness than the IMs Sa(T1) and Sa¯.

Objective To evaluate the placement feasibility and safety of the newly designed retropharyngeal reduction plate by cadaveric test and to perform morphometric trajectory analysis. Methods The five cadaveric specimens with intact atlantoaxial joint were enrolled in this study. They were used for simulating the placement process and evaluating the placement feasibility of the retropharyngeal reduction plate. The atlantoaxial dislocation (AAD) of five cadaveric specimens were obtained by proper external force after dissecting ligaments. The retropharyngeal reduction plate was placed on atlantoaxial joint of cadaveric specimens. The X‐ray and three‐dimensional (3D) spiral CT were used for evaluating the placement safety of retropharyngeal reduction plate. The DICOM data was obtained after 3D spiral CT scanning for the morphometric trajectory analysis. Results The reduction plates were successfully placed on the atlantoaxial joint of five cadaveric specimens through the retropharyngeal approach, respectively. The X‐ray and 3D spiral CT showed the accurate screw implantation and satisfying plate placement. The length of the left/right atlas screw trajectory (L/RAT) was, respectively, 1.73 ± 0.01 cm (LAT) and 1.71 ± 0.02 cm (RAT). The length of odontoid screw trajectory (OST) was 1.38 ± 0.02 cm. The length of the left/right axis screw trajectory (L/RAXT) was, respectively, 1.67 ± 0.02 cm (LAXT) and 1.67 ± 0.01 cm (RAXT). There was no statistical significance between left side and right side in terms of AT and AXT (P > 0.05). The angles of atlas screw trajectory angle (ASTA), axis screw trajectory angle (AXSTA), and odontoid screw trajectory angle (OSTA) were 38.04° ± 2.03°, 56.92° ± 2.66°, and 34.78° ± 2.87°, respectively. Conclusion The cadaveric test showed that the retropharyngeal reduction plate is feasible to place on the atlantoaxial joint, which is also a safe treatment choice for atlantoaxial dislocation. The meticulous preoperative planning of screw trajectory based on individual differences was also vital to using this technique.

AIM: To describe the clinical heterogeneity of patients with novel mutations in BEST1. METHODS: All the members in the two Chinese families underwent detailed clinical evaluations including best-corrected visual acuity, slit-lamp examination, applanation tonometry, and dilated fundus examination. Fundus autofluorescence, fundus fluorescein angiography, spectral-domain optical coherence tomography, electrooculography, and electroretinogram were also performed. Genomic DNA was extracted from venous blood for all the participants. The targeted next-generation sequencing of inherited retinal disease-associated genes was conducted to identify the causative mutation. RESULTS: A novel BEST1 missense mutation c.41T>C (p.Leu14Ser) was identified in Family 1. It was co-segregated with the phenotype of best vitelliform macular dystrophy (BVMD) and bioinformatics analysis confirmed it was harmful. Another novel BEST1 frameshift mutation c.345_346insGGCAAGGACG (p.Glu119Glyfs*116) and a novel USH2A missense mutation c.12560G>A, p.Arg4187His were identified in family 2 with retinitis pigmentosa (RP), which might interact and lead to the phenotype of RP. CONCLUSION: Two novel mutations in the BEST1 gene in two unrelated families with distinct phenotypes and BEST1 mutation accompanied with USH2A mutation would result in RP, which could be enormously helpful in understanding the pathogenesis of the inherited retinal disease caused by a BEST1 mutation.

Abstract Seed deterioration during rice seed storage can lead to seed vigor loss, which adversely affects agricultural production, the long-term preservation of germplasm resources, and the conservation of species diversity. However, the mechanisms underlying seed vigor maintenance remain largely unknown. In this study, 16 hybrid rice combinations were created using four sterile lines and four restorer lines that have been widely planted in southern China. Following artificial aging and natural aging treatments, germination percentage and metabolomics analysis by gas chromatography–mass spectrometry was used to identify the metabolite markers that could accurately reflect the degree of aging of the hybrid rice seeds. Significant differences in the degree of seed deterioration were observed among the 16 hybrid rice combinations tested, with each hybrid combination having a different germination percentage after storage. The hybrid rice combination with the storage-resistant restorer line Guanghui122 exhibited the highest germination percentage under both natural and artificial storage. A total of 89 metabolic peaks and 56 metabolites were identified, most of which were related to primary metabolism. Interestingly, the content of galactose, gluconic acid, fructose and glycerol in the seeds increased significantly during the aging process. Absolute quantification indicated that galactose and gluconic acid were highly significantly negatively correlated with the germination percentage of the seeds under the different aging treatments. The galactose content was significantly positively correlated with gluconic acid content. Additionally, glycerol showed a significant negative correlation with the germination percentage in most hybrid combinations. Based on the metabolomics analysis, metabolite markers that could accurately reflect the aging degree of hybrid rice seeds were identified. Galactose and gluconic acid were highly significantly negatively correlated with the germination percentage of the seeds, which suggested that these metabolites could constitute potential metabolic markers of seed vigor and aging. These findings are of great significance for the rapid and accurate evaluation of seed aging degree, the determination of seed quality, and the development of molecular breeding approaches for high-vigor rice seeds.

Frost damage to concrete can make concrete beams more vulnerable under seismic forces. However, research on the seismic performance of frost-damaged reinforced concrete (RC) beams is still in its infancy. In this paper, the effects of freeze–thaw cycles (FTCs) and concrete strength on the seismic performance of frost-damaged RC beams are studied using an artificial rapid freeze–thaw climate and pseudo–static test in sequence. The seismic resistance of frost-damaged RC beams is assessed in the following respects: general damage behavior and failure pattern, hysteresis response, displacement, strength, cumulative energy consumption, and shear component. It turns out that, with the increase in the number of FTCs (NFTCs), the load and displacement under different characteristic states, ductility ratio, and cumulative energy consumption decrease stage by stage, while the shear distortion and the contribution of shear displacement under the entire cyclic loading process are progressively enhanced. Simultaneously, the strength of the cracking point is more susceptible to FTC action than to yield and peak points, and the declining rate of strength under different characteristic points gradually increases. Based on the test results, a calculation formula for the skeleton curve of frost-damaged RC beam–column is established, taking the influences of the pristine concrete strength, NFTCs, and axial force ratio into account.

In this research, a series of 3-(pyridine-3-yl)-2-oxazolidinone derivatives was designed, synthesized, and evaluated for in vitro antibacterial activity, which included bacteriostatic, morphological, kinetic studies, and molecular docking. The results demonstrated that compounds 21b, 21d, 21e and 21f exhibited strong antibacterial activity similar to that of linezolid toward five Gram-positive bacteria. After observing the effect of the drug on the morphology and growth dynamics of the bacteria, the possible modes of action were predicted by molecular docking. Furthermore, the antibiofilm activity and the potential drug resistance assay was proceeded. These compounds exhibited universal antibiofilm activity and compound 21d showed significant concentration-dependent inhibition of biofilm formation. Compound 21d also showed a stable effect on S. pneumoniae (ATCC 49619) with less drug resistance growth for 15 days, which is much longer than that of linezolid. Overall, these results can be used to guide further exploration of novel antimicrobial agents.

Arteriosclerosis obliterans (ASO) is characterized by arterial narrowing and blockage due to atherosclerosis, influenced by endothelial dysfunction and inflammation. This research focuses on exploring the role of MAGOH-DT, a long noncoding RNA, in mediating endothelial cell dysfunction through endothelial-mesenchymal transition (EndMT) under inflammatory and hyperglycemic stimuli, aiming to uncover potential therapeutic targets for ASO. Differential expression of lncRNAs, including MAGOH-DT, was initially identified in arterial tissues from ASO patients compared to healthy controls through lncRNA microarray analysis. Validation of MAGOH-DT expression in response to tumor necrosis factor-alpha (TNF-α) and high glucose (HG) was performed in human umbilical vein endothelial cells (HUVECs) using RT-qPCR. The effects of MAGOH-DT and HNRPC knockdown on EndMT were assessed by evaluating EndMT markers and TGF-β2 protein expression with Western blot analysis. RNA-immunoprecipitation assays were used to explore the interaction between MAGOH-DT and HNRPC, focusing on their role in regulating TGF-β2 translation. In the results, MAGOH-DT expression is found to be upregulated in ASO and further induced in HUVECs under TNF-α/HG conditions, contributing to the facilitation of EndMT. Silencing MAGOH-DT or HNRPC is shown to inhibit the TNF-α/HG-induced increase in TGF-β2 protein expression, effectively attenuating EndMT processes without altering TGF-β2 mRNA levels. In conclusion, MAGOH-DT is identified as a key mediator in the process of TNF-α/HG-induced EndMT in ASO, offering a promising therapeutic target. Inhibition of MAGOH-DT presents a novel therapeutic strategy for ASO management, especially in cases complicated by diabetes mellitus. Further exploration into the therapeutic implications of MAGOH-DT modulation in ASO treatment is warranted. [ABSTRACT FROM AUTHOR]

Endothelial-to-mesenchymal transition (EndMT), the process by which an endothelial cell (EC) undergoes a series of molecular events that result in a mesenchymal cell phenotype, plays an important role in atherosclerosis. 1-Palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC), derived from the oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine, is a proinflammatory lipid found in atherosclerotic lesions. Whether POVPC promotes EndMT and how simvastatin influences POVPC-mediated EndMT remains unclear. Here, we treated human umbilical vein ECs with POVPC, simvastatin, or both, and determined their effect on EC viability, morphology, tube formation, proliferation, and generation of NO and superoxide anion (O2•−). Expression of specific endothelial and mesenchymal markers was detected by immunofluorescence and immunoblotting. POVPC did not affect EC viability but altered cellular morphology from cobblestone-like ECs to a spindle-like mesenchymal cell morphology. POVPC increased O2− generation and expression of alpha-smooth muscle actin, vimentin, Snail-1, Twist-1, transforming growth factor-beta (TGF-β), TGF-β receptor II, p-Smad2/3, and Smad2/3. POVPC also decreased NO production and expression of CD31 and endothelial NO synthase. Simvastatin inhibited POVPC-mediated effects on cellular morphology, production of O2•− and NO, and expression of specific endothelial and mesenchymal markers. These data demonstrate that POVPC induces EndMT by increasing oxidative stress, which stimulates TGF-β/Smad signaling, leading to Snail-1 and Twist-1 activation. Simvastatin inhibited POVPC-induced EndMT by decreasing oxidative stress, suppressing TGF-β/Smad signaling, and inactivating Snail-1 and Twist-1. Our findings reveal a novel mechanism of atherosclerosis that can be inhibited by simvastatin.

By introducing the orbital angular momentum (OAM) eigenfunctions of the pulsed beam and two-frequency mutual coherence function in oceanic turbulence, we establish the received probability distribution of OAM modes of the ultrashort Laguerre-Gaussian pulsed beam propagating through oceanic turbulence. Our results show that the higher rate of dissipation of kinetic energy per unit mass of fluid, larger inner scale, smaller ratio of temperature and salinity contributions to the refractive index spectrum, or lower dissipation rate of the mean-squared temperature will cause the smaller pulse duration by its full-width half-maximum. The pulse duration has a weak dependence on the OAM quantum number. In addition, the smaller OAM quantum number and the larger transmission distance cause the smaller pulse delay. Our results will be useful for vortex pulsed beam in the optical ocean communication and remote sensing. Keywords: Vortex beams, Pulse, Oceanic turbulence, Orbital angular momentum, Optical communication

Developmental dyslexia is a complex reading and writing disorder with strong genetic components. In previous genetic studies about dyslexia, a number of candidate genes have been identified. These include DCDC2, which has repeatedly been associated with developmental dyslexia in various European and American populations. However, data regarding this relationship are varied according to population. The Uyghur people of China represent a Eurasian population with an interesting genetic profile. Thus, this group may provide useful information about the association between DCDC2 gene polymorphisms and dyslexia. In the current study, we examined genetic data from 392 Uyghur children aged 8–12 years old from the Xinjiang Uyghur Autonomous Region of China. Participants included 196 children with dyslexia and 196 grade-, age-, and gender-matched controls. DNA was isolated from oral mucosal cell samples and fourteen single nucleotide polymorphisms (rs6456593, rs1419228, rs34647318, rs9467075, rs793862, rs9295619, rs807701, rs807724, rs2274305, rs7765678, rs4599626, rs6922023, rs3765502, and rs1087266) in DCDC2 were screened via the SNPscan method. We compared SNP frequencies in five models (Codominant, Dominant, Recessive, Heterozygote advantage, and Allele) between the two groups by means of the chi-squared test. A single-locus analysis indicated that, with regard to the allele frequency of these polymorphisms, three SNPs (rs807724, rs2274305, and rs4599626) were associated with dyslexia. rs9467075 and rs2274305 displayed significant associations with developmental dyslexia under the dominant model. rs6456593 and rs6922023 were significantly associated with developmental dyslexia under the dominant model and in the heterozygous genotype. Additionally, we discovered that the T-G-C-T of the four-marker haplotype (rs9295619-rs807701-rs807724-rs2274305) and the T-A of the two-marker haplotype (rs3765502-1087266) were significantly different between cases and controls. Thus, we conclude that DCDC2 gene polymorphisms are associated with developmental dyslexia in Chinese Uyghur children.

This study focuses on the impact of regional land use land morphology on carbon emissions from a regional perspective. The study first quantifies the land morphology of the Yangtze River Delta region from 2005 to 2017 by calculating a series of parameters. These parameters include city scale, shape complexity, shape fragmentation, spatial aggregation and spatial diversity. Then, a panel data model of these parameters and overall urban carbon emissions was developed and analyzed by multiple linear regression. It was found that city scale spatial diversity had significant positive effects on carbon emissions in the Yangtze River Delta region, while the complexity of urban shape had a negative effect. Based on these findings, the study proposes that in terms of overall urban structure, it is necessary to strengthen and improve the degree of compact clustering of morphology and functions, and advocate a highly connected "polycentric" agglomeration cluster model; within cities, the complexity and fragmentation of land morphology should be reduced through a "narrow roads and small blocks" transportation model. [ABSTRACT FROM AUTHOR]

Due to the excellent electrical transmission and potentially excellent thermoelectric (TE) performance, digenite (Cu _1.8 S) has attracted more attentions. The combination of mechanical alloying (MA) and spark plasma sintering (SPS) was widely used in preparing Cu _1.8 S bulk material, while the TE properties for pure sample were still low. Therefore, it’s worth to search a suitable synthesis method to enhance the thermoelectric performance for pristine Cu _1.8 S material. In this study, high-density bulk samples of copper sulfide (CS) were fabricated by solid states reaction method combined with SPS at different temperatures. When the SPS temperature was over 873 K, large amounts of sulfur volatilization lead to the appearance of Cu _1.96 S second phase and it was considered to have great influence on the thermoelectric performances. The result reveals that the increased sintering temperature could affect the density and grain size of the bulk samples. The highest ZT value of 0.54 was obtained at 773 K for the sample sintered at 773 K, which is also the highest ZT value for the pristine Cu _1.8 S in the literature.

Keloid scars are often considered aesthetically unattractive and frustrating problems that occur following injuries. They cause functional and cosmetic deformities, displeasure, itching, pain, and psychological stress and possibly affect joint movement. The combination of these factors ultimately results in a compromised quality of life and diminished functional performance. Various methods have been implemented to improve keloid scars using both surgical and non-surgical approaches. However, it has proven to be a challenge to identify a universal treatment that can deliver optimal results for all types of scars. Through a PubMed search, we explored most of the literature that is available about the intralesional injection treatment of hypertrophic scars and keloids and highlights both current (corticosteroid, 5-fluorouracil, bleomycin, interferon, cryotherapy and verapamil) and future treatments (interleukin-10 and botulinum toxin type A). The reference lists of retrieved articles were also analysed. Information was gathered about the mechanism of each injection treatment, its benefits and associated adverse reactions, and possible strategies to address adverse reactions to provide reliable guidelines for determining the optimal treatment for particular types of keloid scars. This article will benefit practitioners by outlining evidence-based treatment strategies using intralesional injections for patients with hypertrophic scars and keloids.

Abstract Background Recent studies have demonstrated that synthetic dsRNAs may produce therapeutic effects in a target-independent manner through stimulation of the toll-like receptor-3 (TLR3)/interferon pathway; as a result, angiogenesis and proliferation of tumor cells are inhibited. Thus, this pathway may become a potential target of dsRNA in tumor suppression. In this study, we evaluated the role of synthetic dsRNA as a TLR3 synergist and by combining with sorafenib in anti-hepatocellular carcinoma (HCC) in vitro and in vivo. Methods Four dsRNAs were designed and synthesized. One of them that was capable of activating TLR3 most effectively in human HCC cell line (HepG2.2.15) was selected as a TLR3 synergist (called BM-06). Subsequently, the expression of proteins relating to TLR3 signaling pathway, such as NF-κB, caspase 8 survivin, bcl-2 and PCNA affected by BM-06, sorafenib alone or in combination, was compared. The migration, proliferation and apoptosis of HepG2.2.15 cells were evaluated in presence of BM-06, sorafenib alone or in combination of both. The similar treatments were also applied in an SD rat primary HCC model. Results qRT-PCR data showed that the expression of TLR3 and NF-κB in HepG2.2.15 cells was enhanced. BM-06 was selected as a TLR3 synergist capable of activating the TLR3/interferon pathway most effective among 4 synthetic dsRNAs. The migration and proliferation were significantly inhibited in treated HepG2.2.15 cells with BM-06 or Sorafenib alone as compared with PBS-sham control (P

BackgroundA thinned anterolateral thigh (ALT) flap is often harvested to achieve optimal skin resurfacing. Several techniques have been described to thin an ALT flap including an adipocutaneous flap, an adipofascial flap and delayed debulking.MethodsBy systematically reviewing all of the available literature in English and French, the present manuscript attempts to identify the common surgical indications, complications and donor site morbidity of the adipofascial variant of the ALT flap. The studies were identified by performing a systematic search on Medline, Ovid, EMBASE, the Cochrane Database of Systematic Reviews, Current Contents, PubMed, Google, and Google Scholar.ResultsThe study selection process was adapted from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, and 15 articles were identified using the study inclusion criteria. These articles were then reviewed for author name(s), year of publication, flap dimensions and thickness following defatting, perforator type, type of transfer, complications, thinning technique, number of cases with a particular area of application and donor site morbidity.ConclusionsThe adipofascial variant of the ALT flap provides tissue to fill large defects and improve pliability. Its strong and safe blood supply permits adequate immediate or delayed debulking without vascular complications. The presence of the deep fascia makes it possible to prevent sagging by suspending and fixing the flap for functional reconstructive purposes (e.g., the intraoral cavity). Donor site morbidity is minimal, and thigh deformities can be reduced through immediate direct closure or liposuction and direct closure. A safe blood supply was confirmed by the rate of secondary flap debulking.

Objective To explore the clinical features, genetic characters and the importance of prenatal diagnosis in spinocerebellar ataxia 3 (SCA3) patients. Methods SCA3/ATXN3 gene was determined by using PCR and segmental analysis techniques in 2 patients among a SCA3 Chinese Han family which included 9 patients in four generations. One patient was the proband's fetus. The clinical characters were also documented and analyzed in this family. Results There were 9 patients in this family with autosomal dominant inheritance feature. The initial symptoms in all affected members except the fetus were the gait disorders accompanied by dysphasia. Inability of upward gaze and bilateral Barbinski's signs were noted in proband. The onset age became earlier from generation to generation in this family which was around 50 year⁃old, 40 to 45 year⁃old, 28 year⁃old in generation Ⅰ, Ⅱ and Ⅲ, respectively. CAG repeats in SCA3/ATXN3 allele were 77 in proband, as well as in the fetus, while the normal SCA3/ATXN3 allele CAG repeats were less than 44. Conclusion SCA3 is the most frequent subtype of SCA in Asian. Unsteadiness of gait are first noted in most patients accompanied by other different symptoms and signs. Genetic anticipation was found in SCA3. But gene analysis revealed less dynamic mutation frequence in this family. Since there was no effective treatment in SCA3, hereditary consultation and prenatal diagnosis play an important role in disease prevention and hereditary. DOI：10.3969/j.issn.1672⁃6731.2012.03.010

Three new pimarane diterpenes, eutypellenoids A–C (1–3), together with a known compound, eutypenoid C (4), were isolated from the culture extract of Eutypella sp. D-1 derived from the Arctic region. Compounds 1–3 possessed an uncommon tetrahydrofuran-fused pimarane diterpene skeleton. The structures of all compounds were determined by detailed spectroscopic analysis, electronic circular dichroism (ECD) analysis, as well as a comparison with the literature data. Antibacterial, antifungal, and cytotoxic activities of these compounds were evaluated. Compound 2 displayed antibacterial activity against Staphylococcus aureus and Escherichia coli with MIC values of 8 and 8 μg/mL, respectively. Additionally, compound 2 showed antifungal activity against Candida parapsilosis, Candida albicans, Candida glabrata, and Candida tropicalis with MIC values of 8, 8, 16, and 32 μg/mL, respectively. Furthermore, compound 2 exhibited moderate cytotoxic activity against HCT-116 cell line with IC50 value of 3.7 μM.

Background: In the last 3 decades, liposuction has become a mainstay of the plastic surgeon’s armamentarium, and the technique has evolved considerably. We retrospectively review all of the liposuction procedures that we performed over the past 20 years. Methods: The principles of superficial 3-dimensional liposuction with respect to preoperative, intraoperative, and postoperative management of patients scheduled to undergo liposuction of the hips, flanks, and thighs were described. Results: A total of 4000 patient charts were reviewed. The results indicated that 50 patients experienced a postsurgical seroma that was resolved after syringe aspirations. One patient developed a major mycobacterial infection that was resolved after antibiotic therapy. Twenty patients complained of minor asymmetries that were corrected 6 months later under local anesthesia; 18 patients suffered from minor skin irregularities, which improved after lipofilling. In 6 cases, transient hyperpigmentation (6–12 months) of the skin before the use of suction drainages in the removal of large adiposities in patients with light skin was experienced, and in 2 cases, transient paresthesia (8 and 10 months) was experienced. No skin necrosis, deep vein thrombosis, or death occurred. Conclusions: If performed correctly, 3-dimensional superficial liposuction of the trunk, hips, and thighs can yield very satisfying outcomes because of the excellent contour and the enhanced skin retraction provided by the thin cutaneous adipose flap. Three-dimensional liposuction is a reliable method with proven results. A careful application of the technique combined with accurate surgical planning, a thorough preoperative explanation of real expectations, and postoperative care is crucial.

The aim of this study is to explore the inhibitory effects of RNA interference (RNAi) targeting NET-1 or combined with sorafenib on HCC in vitro and in vivo and the possible underlying mechanisms. The expressions of NET-1 mRNA and protein were detected by RT-QPCR and western blot. The ability of proliferation was determined by CCK-8 assay. Apoptosis was examined by flow cytometry (FCM). Abilities of migration and invasion were measured by scratch-wound assay and transwell assay. MHCC97H cells with stable transfection of NET-1shRNA were injected subcutaneously to prepare nude mice model of HCC and Caspase-3, Caspase-8, and Caspase-9 mRNAs of tumor tissues in different groups were examined. NET-1 mRNA and protein were reduced sharply in MHCC97H cells transfected with NET-1shRNA. The abilities of proliferation and migration were inhibited and apoptosis was promoted in either NET-1shRNA or sorafenib as compared with untreated cells in vitro and in vivo (P

Background. Recent studies suggest that mutation of the slow delayed rectifier potassium channel (IKs) contributes to familial atrial fibrillation (FAF). In the current study, we identified common genetic variants of KCNQ1 and explored the potential association between KCNQ1 polymorphism with lone AF (LAF). Methods. Clinical data and blood samples were collected from 190 Han Chinese patients with sporadic AF and matched healthy controls. Variants of the KCNQ1 gene were identified using single-strand conformational polymorphism (SSCP) analysis. A case-control association study in KCNQ1 identified six known single-nucleotide polymorphisms (SNPs) during SSCP screening of the 190 LAF patients and 190 healthy controls. Results. One of the SNPs in KCNQ1 was strongly associated with LAF; significant allelic association was detected rs59233444 (P=0.013, OR=1.469, 95% confidence interval (CI): 1.083–1.993). A multiple regression analysis indicated that rs59233444 is an independent risk factor for LAF. Twelve new variants were identified in KCNQ1, including one in the 5′-UTR, two in the 3′-UTR, six in introns, two synonymous substitutions, and one missense substitution. Variants c.1009C>T, c.1860C>T, and c.+2285C>T were not present in the 190 controls, and the others were identified in controls at various frequencies. Conclusions. rs59233444, a common SNP but not mutation in the coding regions of the KCNQ1 gene, is a risk factor for LAF in Chinese Han population.

The veined rapa whelk (Rapana venosa) is an economically important gastropod in China, but is considered as an invasive species globally. Only a few studies have examined the R. venosa genome, a genomewide survey is necessary for improving our understanding of the genome structure and size of this organism. Microsatellite markers are powerful tools for characterizing germplasms, genetic diversity and kinship among individuals. The resultant data are applicable to breeding efforts in commercial aquaculture or for understanding invasion mechanisms. Here, we investigated the genome structure of R. venosa on an Illumina Hi-seq platform with ∼92× sequencing depth. We performed a K-mer analysis to estimate genome size, repeat sequences and heterozygosity. Clean reads were de novo assembled for the identification of simple-sequence repeat (SSR) loci that are suitable as markers. The estimated genome size of R. venosa was 2200.07 Mb, with a 1.41% heterozygosity rate and 67.04% repeats. We detected 5,477,450 simple-sequence repeats (SSRs), with 3,400,602 loci present as pure tandem repeats and 2,076,848 as compound motifs. We further selected and characterized 28 polymorphic markers in 78 individuals from Dandong, Laizhou, Weihai and Zhoushan in China. The range of alleles was 2-28 and the observed heterozygosity was 0.2857-0.8676. The data obtained from our genomic survey will aid the design of R. venosa whole-genome sequencing projects and advance the identification of SSR markers. Both these developments are valuable for further studies on ecological, evolutionary and genetic breeding in R. venosa. [ABSTRACT FROM AUTHOR]

Background The vascularization of the distal portions of transferred tissue represents the most critical factor in the success of reconstructive surgery. In recent years, indocyanine green (ICG) fluorescence imaging techniques have been applied during surgery to evaluate flap perfusion. However, this investigation has found that there is little consensus regarding the standard dose of ICG as well as the pre-operative requirements of ICG allergy testing. The aim of this study is to summarize the applications of ICG to tissue transfers and safe dosing practices and to provide insight to the possible adverse effects of ICG on flap surgery with the goal of helping clinicians apply ICG safely and efficiently to tissue transfer procedures. Methods A literature search was performed using, Wiley InterScience, and Springer with the key words, 'Flap,' 'indocyanine green,' 'surgery,' and related mesh words for all publications between 2005 and 2015. Title and abstract screening was performed using predefined in- and exclusion criteria. Results Seventy-three articles were included. These were classified as "application of ICG in flap surgery" and "the security of applying ICG in flap surgery". Conclusions ICG fluorescence imaging preoperatively facilitates the detection of perforators in tissue flaps with thickness <20 mm, aids in the evaluation of flap microcirculation and perfusion, and allows surgeons to select dominant cutaneous nerves while evaluating the quality of vascular anastomoses and locating thromboses. The literature also concluded that potential allergic reactions to ICG should be taken into consideration. [ABSTRACT FROM AUTHOR]

An environment-friendly graphene reinforced slag-based nanocomposite (GRSN) was synthesized by incorporation of two-dimensional lamellar graphene into the alkali-activated blast-furnace slag-based cementitious-material (ABSC), and firstly used as an excellent catalyst for solar photocatalytic hydrogen generation. The mechanical testing results indicated that the compressive and flexural strengths of ABSC were prominently reinforced by the incorporation of graphene. The X-ray diffraction (XRD) results showed that the GRSN powder mainly contained the network structure of calcium silicate hydrate (CSH) and calcium aluminate hydrate (CAH). The photoluminescence spectra implied that the separation efficiency of photo-excited electrons and holes increased with the increasing graphene. The yield of hydrogen gradually ascended with the amount of graphene incorperated. The highest H2 yield of 1928.6 µmol/g for 0.02GRSN sample is ascribed to the synergistic effect of graphene and semiconductor oxides of TiO2 and Fe2O3 deriving from the ABSC. [ABSTRACT FROM AUTHOR]

Population-based cancer survival is an improved index for evaluating the overall efficiency of cancer health services in a given region. The current study analysed the observed survival and relative survival of leading cancer sites from a population-based cancer registry between 1972 and 2011 in Qidong, China. A total of 92,780 incident cases with cancer were registered and followed-up for survival status. The main sites of the cancer types, based on the rank order of incidence, were the liver, stomach, lung, colon and rectum, oesophagus, breast, pancreas, leukaemia, brain and central nervous system (B and CNS), bladder, blood [non-Hodgkin's lymphoma (NHL)] and cervix. For all malignancies combined, the 5-year observed survival was 13.18% and the relative survival was 15.80%. Females had higher observed survival and relative survival (19.32 and 22.71%, respectively) compared with males (9.63 and 11.68%, respectively). The cancer sites with the highest five-year relative survival rates were the female breast, bladder, cervix and colon and rectum; followed by NHL, stomach, B and CNS cancer and leukaemia. The poorest survival rates were cancers of oesophagus, lung, pancreas and liver. Higher survival rates were observed in younger patients compared with older patients. Cancers of the oesophagus, female breast and bladder were associated with higher survival in middle-aged groups. Improved survival rates in the most recent two 5-year calendar periods were identified for stomach, lung, colon and rectum, oesophagus, female breast and bladder cancer, as well as leukaemia and NHL. The observations of the current study provide the opportunity for evaluation of the survival outcomes of frequent cancer sites that reflects the changes and improvement in a rural area in China. [ABSTRACT FROM AUTHOR]

Glioblastoma is the mostcommonmalignant brain tumor and has a poor prognosis. Tachykinin receptor neurokinin-1 (NK1R) is a promising target in glioblastoma therapy because of its overexpression in human glioblastoma. NK1R agonists promote glioblastoma cell growth, whereas NK1R antagonists efficiently inhibit cell growth both in vitro and in vivo. However, the molecular mechanisms involved in these effects are incompletely understood. β-Arrestins (ARRBs) serve as scaffold proteins and adapters to mediate intracellular signal transduction. Here we show that the ARRB1-mediated signaling pathway is essential for NK1-mediated glioblastoma cell proliferation. ARRB1 knockdown significantly inhibited NK1-mediated glioblastoma cell proliferation and induced G2/M phase cell cycle arrest. ARRB1 knockdown cells showed remarkable down-regulation of CDC25C/CDK1/cyclin B1 activity. We also demonstrated that ARRB1 mediated prolonged phosphorylation of ERK1/2 and Akt in glioblastoma cells induced by NK1R activation. ERK1/2 and Akt phosphorylation are involved in regulating CDC25C/CDK1/cyclin B1 activity. The lack of long-term ERK1/2 and Akt activation in ARRB1 knockdown cells was at least partly responsible for the delayed cell cycle progression and proliferation. Moreover, we found that ARRB1-mediated ERK1/2 and Akt phosphorylation regulated the transcriptional activity of both NF-κB and AP-1, which were involved in cyclin B1 expression. ARRB1 deficiency increased the sensitivity of glioblastoma cells to the treatment of NK1R antagonists. Taken together, our results suggest that ARRB1 plays an essential role in NK1R-mediated cell proliferation and G2/M transition in glioblastoma cells. Interference with ARRB1-mediated signaling via NK1R may have potential significance for therapeutic strategies targeting glioblastoma. [ABSTRACT FROM AUTHOR]

Background Limited flap survival area is the main disadvantage of prefabricated flaps. To deal with this problem, surgical delay is the common method to achieve a better prognosis. This method requires multiple surgeries with the known associated burdens. We have developed a new strategy, ex vivo delay, utilizing the pathophysiology of surgical delay while avoiding the need for multiple surgeries. Methods We created a rodent animal model utilizing a two-stage operation of a prefabricated abdominal flap. The rats were randomly divided into three groups (n = 6 per group): group A, the control group (no intervention), group B, delayed by the ex-vivo delay device, and group C, delayed using surgical delay technique. Data were collected according to macroscopic analysis, near-infrared fluorescence imaging, and capillary densities. Results According to the macroscopic analysis, groups B and C had a significantly larger flap survival area compared with group A, but group B had a significantly smaller survival area than group C. The near-infrared fluorescence imaging showed the perfusion areas of group B and C to be larger than that of group A. Histologically, groups B and C had a significantly higher capillary density than group A. The vessel caliber in group C was larger than that of groups A and B. Conclusions The ex vivo delay strategy successfully increased flap survival area. This strategy worked by establishing ischemia and enhancing neovascularization. Further improvements in the surgical technique could produce outcomes similar to those seen with surgical delay. [ABSTRACT FROM AUTHOR]

Aims Atrial fibrillation (AF) is a common arrhythmia with an important heritable aspect. The genetic factors underlying AF have not been fully elucidated. Methods and results We screened six candidate genes (CAV1, KCNJ2, KCNQ1, NKX2.5, PITX2, and TBX5) for novel mutations in 139 patients of Chinese descent with early-onset AF and 576 controls. Four missense TBX5 mutations, p.R355C, p.Q376R, p.A428S, and p.S372L, were identified in evolutionarily conserved regions. We did not find any mutations in CAV1, KCNJ2, KCNQ1, NKX2.5, and PITX2. These mutations increased the expression of atrial natriuretic peptide (ANP) and connexin-40 (CX40) in the primarily cultured rat atrial myocytes but did not alter the expression of cardiac structural genes, atrial myosin heavy chain-α (MHC-α) and myosin lightchain-2α (MLC-2α). Overexpression of p.R355C developed an atrial arrhythmia suggestive of paroxysmal AF in the zebrafish model. To replicate our findings, we screened TBX5 in 527 early-onset AF cases from the Massachusetts General Hospital AF study. A novel TBX5 deletion (ΔAsp118, p.D118del) was identified, while no TBX5 mutations were identified in 1176 control subjects. Conclusion Our results provide both genetic and functional evidence to support the contribution of TBX5 gene in the pathogenesis of AF. The potential mechanism of arrhythmia may be due in part to the disturbed expression of ANP and CX40. [ABSTRACT FROM AUTHOR]

Background: We present the clinical application of the sixth internal mammary artery perforator (IMAP) and superior epigastric artery perforator (SEAP) flaps for the treatment of defects resulting from the excision of large lower sternal and upper abdominal keloids. Perforator selection and flap design were based solely on preoperative multidetector-row computed tomographic angiography (MDCTA) of the areas adjacent to the soft tissue defects. Methods: Between January 2009 and June 2014, 15 patients with large, unstable keloids subject to recurrent inflammation and infections and with a history of multiple failed treatments underwent surgical excision and early postoperative radiation therapy. The defects were located in the upper abdomen (n = 6) or lower sternum (n = 9). All patients underwent preoperative MDCTA for perforator localization. Results: A total of 15 patients underwent keloid removal followed by IMAP (n = 10) and SEAP (n = 6) flap coverage combined with early postoperative low-dose radiation therapy (350 cGy/5 fractions/5 days or 400 cGy/4 fractions/4 days). Flap sizes ranged from 9 × 5 to 17 × 6 cm. Only one IMAP flap developed a 2 × 2 cm tip necrosis, which was managed with dressing changes. The remaining flaps healed uneventfully with no keloid recurrence at 23.4 months. In all cases, the perforator location determined by preoperative MDCTA was precisely consistent with the intraoperative findings. Conclusion: The sixth IMAP and SEAP flaps combined with early postoperative radiation therapy provided a valid and feasible approach for the surgical treatment of large keloids in the lower sternal and upper abdominal.MDCTA enabled detailed preoperative assessment of the perforators, facilitating both flap design and dissection, and saving operating time. Although longer follow-up is required, these preliminary results are encouraging. [ABSTRACT FROM AUTHOR]

Background: Totally laparoscopic distal gastrectomy (TLDG) has been developed in the hope of improving surgical quality and overcoming the limitations of conventional laparoscopic assisted distal gastrectomy (LADG) for gastric cancer. The aim of this study was to determine the extent of evidence in support of these ideals. Methods: A systematic review of the two operation types (LADG and TLDG) was carried out to evaluate short-term outcomes including duration of operation, retrieved lymph nodes, estimated blood loss, resection margin status, technical postoperative complications, and hospital stay. Results: Twelve non-randomized observational clinical studies involving 2,255 patients satisfied the eligibility criteria. Operative time was not statistically different between groups (P > 0.05). The number of retrieved lymph nodes and the resection margin length in TLDG were comparable with those in LADG. Estimated blood loss was significantly less in TLDG than that in LAG (P < 0.01). Compared to LADG, TLDG also involved lesser postoperative hospital stay (P < 0.01) and earlier time to soft diet intake (P < 0.05). Time to flatus and postoperative complications were similar for those two operative approaches. Conclusions: TLDG may be a technically safe, feasible, and favorable approach in terms of better cosmesis, less blood loss, and faster recovery compared with LADG. [ABSTRACT FROM AUTHOR]

In vitro and in vivo studies have identified that low-frequency ultrasound (US) and microbubbles (MBs) mediate tumor inhibitory effects. However, the application of US in the clinical setting remains unclear. The aim of the present study was to investigate the clinically therapeutic effect of 20 kHz US in combination with MBs for the treatment of hepatic carcinoma. A 71-year-old male with a hepatic malignant tumor was admitted to Nantong University Affiliated Nantong Tumor Hospital (Nantong, China). The patient was subsequently sonicated with 20 kHz US and MBs over a period of five days. The low-frequency US parameters were set at 20 kHz, 2 W/cm², duty cycle 40% (on 2 sec, off 3 sec) for a duration of 5 min each day for a total of five days. Computed tomography (CT), contrast-enhanced US (CEUS) and carbohydrate antigen 19-9 (CA19-9) tests were performed to evaluate the therapeutic effects. Although the tumor size increased marginally on CT from 5.4 to 5.6 cm after US treatment, the intensity and enhanced-areas on the CT scans and CEUS decreased. The abdominal lymph node decreased in size, from 2.2 to 1.9 cm, and CA19-9 levels decreased from the pretreatment value of 2,007 to 734 U/ml. Therapy with low-frequency US combined with MBs may exhibit an anti- vasculature effect and may be used as a palliative treatment for patients with unresectable hepatic malignant tumors. [ABSTRACT FROM AUTHOR]