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Abstract Background Melanoma proliferation is partly attributed to dysregulated lipid metabolism. The effectiveness of lipid-lowering drugs in combating cutaneous melanoma (CM) is a subject of ongoing debate in both in vitro and clinical studies. Method This study aims to evaluate the causal relationship between various lipid-lowering drug targets, namely 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR, targeted by statins), Proprotein convertase subtilisin/kexin type 9 (PCSK9, targeted by alirocumab and evolocumab), and Niemann-Pick C1-like 1 (NPC1L1, targeted by ezetimibe), and the outcomes of cutaneous melanoma. To mimic the effects of lipid-lowering drugs, we utilized two genetic tools: analysis of polymorphisms affecting the expression levels of drug target genes, and genetic variations linked to low-density lipoprotein cholesterol levels and drug target genes. These variations were sourced from genome-wide association studies (GWAS). We applied Summary-data-based Mendelian Randomization (SMR) and Inverse Variance Weighted Mendelian Randomization (IVW-MR) to gauge the effectiveness of these drugs. Results Our findings, with SMR results showing an odds ratio (OR) of 1.44 (95% CI: 1.08–1.92; P = 0.011) and IVW-MR results indicating an OR of 1.56 (95% CI: 1.10–2.23; P = 0.013), demonstrate a positive correlation between PCSK9 expression and increased risk of CM. However, no such correlations were observed in other analyses. Conclusion The study concludes that PCSK9 plays a significant role in the development of CM, and its inhibition is linked to a reduced risk of the disease.

ObjectivesChina’s National Health Service Items Standard (NHSIS) establishes a relative value system and plays an important role in pricing. However, there are few empirical evaluations of the objectivity of the NHSIS-estimated relative value.MethodsThis paper presents a comparison between physician work relative value units (wRVUs) estimates for 70 common surgical procedures from NHSIS and those from the U.S. Medicare Physician Fee Schedule (MPFS). We defined the ratio of the wRVUs for sample procedures to the benchmark procedure (inguinal hernia repair) as a standardized relative value unit (SRVU), which was used to standardize the data for both schedules. We examined the variances in the ranking and quantification of SRVUs across specialties and procedures, as well as how SRVUs impact procedure reimbursement prices between the two schedules.ResultsThere was no systematic difference between MHSIS-estimated SRVUs and MPFS-estimated, but the dispersion of MPFS-estimated SRVU was greater than that of MHSIS-estimated, and the discrepancies increased with surgical risk and technical complexity. The discrepancies of SRVUs were significant in cardiothoracic procedures. Additionally, whether SRVUs were based on MPFS or MHSIS, there was a positive association between them and payment prices. However, in terms of the impact of SRVUs on payment pricing, the NHSIS system was lower than the MPFS system.ConclusionChina has made incremental progress in estimating the relative value of healthcare services, but there are shortcomings in valuation methods and their impact on pricing. The modular assessment method should be considered as a component to optimize reform.

Burkholderia gladioli pv. cocovenenans is a serious safety issue in black fungus due to the deadly toxin, bongkrekic acid. This has triggered the demand for an efficient toxigenic phenotype recognition method. The objective of this study is to develop an efficient method for the recognition of toxin-producing B. gladioli strains. The potential of multilocus sequence typing and a back propagation neural network for the recognition of toxigenic B. cocovenenans was explored for the first time. The virulent strains were isolated from a black fungus cultivation environment in Qinba Mountain area, Shaanxi, China. A comprehensive evaluation of toxigenic capability of 26 isolates were conducted using Ultra Performance Liquid Chromatography for determination of bongkrekic acid and toxoflavin production in different culturing conditions and foods. The isolates produced bongkrekic acid in the range of 0.05–6.24 mg/L in black fungus and a highly toxin-producing strain generated 201.86 mg/L bongkrekic acid and 45.26 mg/L toxoflavin in co-cultivation with Rhizopus oryzae on PDA medium. Multilocus sequence typing phylogeny (MLST) analysis showed that housekeeping gene sequences have a certain relationship with a strain toxigenic phenotype. We developed a well-trained, back-propagation neutral network for prediction of toxigenic phenotype in B. gladioli based on MLST sequences with an accuracy of 100% in the training set and an accuracy of 86.7% in external test set strains. The BP neutral network offers a highly efficient approach to predict toxigenic phenotype of strains and contributes to hazard detection and safety surveillance.

Soft tissue fabrication using digital light processing remains challenging. Here the authors present a molecular cleavage approach to achieve high-performance bioprinting of constructs with tissue-matching mechanical properties and structural complexity.

Abstract Inaccuracies in intraoperative and preoperative measurements and estimations may lead to adverse outcomes such as patient-prosthesis mismatch. We aim to measure the relation between different dimensions of the atrioventricular valve complex in explanted porcine heart models. After a detailed physical morphology study, a cast of the explanted heart models was made using silicon-based materials. Digital models were obtained from three-dimensional scanning of the casts, showing the measured annulopapillary distance was 2.50 ± 0.18 cm, and 2.75 ± 0.36 cm for anterior and posterior papillary muscles of left ventricle, respectively. There was a significant linear association between the mitral annular circumference to anterior–posterior distance (p = 0.003, 95% CI 0.78–3.06), mitral annular circumference to interpapillary distance (p = 0.009, 95% CI 0.38–2.20), anterior–posterior distance to interpapillary distance (p = 0.02, 95% CI 0.10–0.78). Anterior–posterior distance appeared to be the most important predictor of mitral annular circumference compared to other measured distances. The mean length of the perpendicular distance of the tricuspid annulus, a, was 2.65 ± 0.54 cm; b was 1.77 ± 0.60 cm, and c was 3.06 ± 0.55 cm. Distance c was the most significant predictor for tricuspid annular circumference (p = 0.006, 95% CI 0.28–2.84). The anterior–posterior distance measured by three-dimensional scanning can safely be used to predict the annular circumference of the mitral valve. For the tricuspid valve, the strongest predictor for the circumference is the c-distance. Other measurements made from the positively correlated parameters may be extrapolated to their respective correlated parameters. They can aid surgeons in selecting the optimal prosthesis for the patients and improve procedural planning.

Objective: The beneficial effect of angiotensin(1–7) (Ang(1–7)), via the ac tivation of its receptor, MAS-1, has been noted in diabetes treatment; however, how Ang(1–7) or MAS-1 affects insulin secretion remains elusive and whether the endoge nous level of Ang(1–7) or MAS-1 is altered in diabetic individuals remains unexplored. We recently identified an important role of cystic fibrosis transmembrane conductance regu lator (CFTR), a cAMP-activated Cl− channel, in the regulation of insulin secretion. Here, we tested the possible involvement of CFTR in mediating Ang(1–7)’s effect on insulin se cretion and measured the level of Ang(1–7), MAS-1 as well as CFTR in the blood of in dividuals with or without type 2 diabetes. Methods: Ang(1–7)/MAS-1/CFTR pathway was determined by specific inhibito rs, gene manipulation, Western blotting as well as insulin ELISA in a pancreatic β-cell line, RINm5F. Human blood samples were collected from 333 individuals with (n = 197) and without (n = 136) type 2 diabetes. Ang(1–7), MAS-1 and CFTR levels in the human blood were determined by ELISA. Results: In RINm5F cells, Ang(1–7) induced intracellular cAMP increase, cAMP-response element binding protein (CREB) activation, enhanced CFTR expres sion and potentiated glucose-stimulated insulin secretion, which were abolished by a selective CFTR inhibitor, RNAi-knockdown of CFTR, or inhibition of MAS-1. In human subjects, the blood levels of MAS-1 and CFTR, but not Ang(1–7), were significantly higher in i ndividuals with type 2 diabetes as compared to those in non-diabetic healthy subjects. In addition, blood levels of MAS-1 and CFTR were in significant positive correlation in ty pe-2 diabetic but not non-diabetic subjects. Conclusion: These results suggested that MAS-1 and CFTR as key players in mediating Ang(1–7)-promoted insulin secretion in pancreatic β-cells; MAS-1 and CFTR are positively correlated and both upregulated in type 2 diabetes.

The rare sugar D-allulose is a potential replacement for sucrose with a wide range of health benefits. Conventional production involves the employment of the Izumoring strategy, which utilises D-allulose 3-epimerase (DAEase) or D-psicose 3-epimerase (DPEase) to convert D-fructose into D-allulose. Additionally, the process can also utilise D-tagatose 3-epimerase (DTEase). However, the process is not efficient due to the poor thermotolerance of the enzymes and low conversion rates between the sugars. This review describes three newly identified DAEases that possess desirable properties for the industrial-scale manufacturing of D-allulose. Other methods used to enhance process efficiency include the engineering of DAEases for improved thermotolerance or acid resistance, the utilization of Bacillus subtilis for the biosynthesis of D-allulose, and the immobilization of DAEases to enhance its activity, half-life, and stability. All these research advancements improve the yield of D-allulose, hence closing the gap between the small-scale production and industrial-scale manufacturing of D-allulose.

One approach to cell expansion is to use large hydrogel for growing a large number of cells. Nanofibrillar cellulose (NFC) hydrogel has been used for human induced pluripotent stem cell (hiPSCs) expansion. However, little is known about the status of hiPSCs at the single cell level inside large NFC hydrogel during culture. To understand the effect of NFC hydrogel property on temporal–spatial heterogeneity, hiPSCs were cultured in 0.8 wt% NFC hydrogel with different thicknesses with the top surface exposed to the culture medium. The prepared hydrogel exhibits less restriction in mass transfer due to the presence of macropores and micropores interconnecting the macropores. More than 85% of cells at different depths survive after 5 days of culture inside 3.5 mm thick hydrogel. Biological compositions at different zones inside the NFC gel were examined over time at a single-cell level. A dramatic concentration gradient of growth factors estimated in the simulation along 3.5 mm NFC hydrogel could be a reason for the spatial–temporal heterogeneity in protein secondary structure and protein glycosylation and pluripotency loss at the bottom zone. pH change caused by the lactic acid accumulation over time leads to changes in cellulose charge and growth factor potential, probably another reason for the heterogeneity in biochemical compositions. This study may help to develop optimal conditions for producing high-quality hiPSCs in large nanofibrillar cellulose hydrogel at scale.

Semantic segmentation over three-dimensional (3D) intra-oral mesh scans (IOS) is an essential step in modern digital dentistry. Many existing methods usually rely on a limited number of labeled samples as annotating IOS scans is time consuming, while a large-scale dataset of IOS is not yet publicly available due to privacy and regulatory concerns. Moreover, the local data heterogeneity would cause serious performance degradation if we follow the conventional learning paradigms to train local models in individual institutions. In this study, we propose the FedTSeg framework, a federated 3D tooth segmentation framework with a deep graph convolutional neural network, to resolve the 3D tooth segmentation task while alleviating data privacy issues. Moreover, we adopt a general privacy-preserving mechanism with homomorphic encryption to prevent information leakage during parameter exchange between the central server and local clients. Extensive experiments demonstrate that both the local and global models trained with the FedTSeg framework can significantly outperform models trained with the conventional paradigm in terms of the mean intersection over union, dice coefficient, and accuracy metrics. The FedTSeg framework can achieve better performance under imbalanced data distributions with different numbers of clients, and its overall performance is on par with the central model trained with the full dataset aggregated from all distributed clients. The data privacy during parameter exchange of FedTSeg is further enhanced with a homomorphic encryption process. Our work presents the first attempts of federated learning for 3D tooth segmentation, demonstrating its strong potential in challenging federated 3D medical image analysis in multi-centric settings.

ObjectiveThis study aimed to investigate the effects of long-term hypoxic environment exposure on cognitive ability and neuroimaging characteristics in a highland population in China.MethodsHealth system workers in Maduo County (4,300 m above sea level) and Minhe County (1,700 m above sea level) were selected as research participants and divided into a high-altitude (HA) group and low-altitude (LA) group, respectively. Cognitive ability was assessed using the Montreal Cognitive Assessment (MoCA), Verbal Fluency Test (VFT), Symbol Digit Modalities Test (SDMT), Trail Making Test A and B (TMT), Digit Span Test (DST), and Rey Auditory Verbal Learning Test (RAVLT). All participants underwent a magnetic resonance imaging (MRI) scan, resting state functional MRI scan, and diffusion tensor imaging to clarify changes in regional gray matter (GM) volume, anisotropy index (FA), local consistency (ReHo), and low-frequency oscillation amplitude (ALFF).ResultsThe HA group had significantly lower MoCA, DST, VFT, RAVLT, and TMT scores compared to the control group. No significant differences were found in SDMT score. Furthermore, compared to the LA group, the HA group had significantly lower GM density of the left olfactory cortex, right medial orbital superior frontal gyrus, bilateral insula, left globus pallidus, and temporal lobe (left superior temporal gyrus temporal pole, bilateral middle temporal gyrus temporal pole, and right middle temporal gyrus). In terms of FA, compared with the LA group, the HA group had lower values for the corpus callosum, corpus callosum knee, bilateral radiative corona, and left internal capsule. The HA group had lower ALFF values of the left cerebellum, left putamen, left orbital inferior frontal gyrus, and left precuneus, but higher ALFF values of the left fusiform gyrus, bilateral inferior temporal gyrus, left orbital superior frontal gyrus and medial superior frontal gyrus, compared to the LA group. There was no significant group difference in ReHo values.ConclusionOur findings suggest that a chronic hypoxic environment can induce extensive cognitive impairment. Decreased GM density in multiple brain regions, damaged nerve fibers, and unbalanced neuronal activity intensity in different brain regions may be the structural and functional basis of cognitive impairment due to hypoxia.

In this paper, a color image encryption algorithm based on the fractional-order multi-scroll Chen chaotic system and DNA mutation principle is proposed. The dynamical performances of the fractional-order multi-scroll Chen chaotic system are analyzed by phase diagram, Lyapunov exponential spectrum and bifurcation diagram. Meanwhile, we realized the hardware circuit simulation of the chaotic system on the DSP platform. Based on comprehensive analysis, an image encryption algorithm is designed. In particular, a DNA algorithm with mutation effect has been introduced into the encryption algorithm. Finally, the performances of the designed encryption scheme are analyzed by key space, correlation coefficients, information entropy, histogram, differential attacks and robustness analysis. The experimental results prove that the algorithm has strong encryption capabilities and can withstand multiple decryption methods. The new color image encryption scheme proposed in this paper can realize the secure communication of digital images.

Hydrate plug in the drainage line is a serious flow assurance problem for the pilot production of offshore natural gas hydrates. Current research focuses on hydrate deposition in the annular flow and the oil-dominated system. The multiphase flow system in the drainage line is a water-dominated system which is normally a bubbly flow. In this work, a new model is developed to study the temperature and pressure field in the drainage line considering that the flow pattern is bubbly flow. Combining with the methane hydrate phase equilibrium curve, the hydrate formation region in the drainage line can be established. The hydrate formation region is enlarged with the ESP pressure increasing and the water production rate decreasing, since the ESP can supply extra pressures in the drainage line and the heat transfer phenomenon is enhanced between the drainage line and environment under the low water production rate condition. The model pointed out that the risk of hydrate formation rises up as the hydrate concentration increases beyond 6%. This study can lay a theoretical foundation for the efficient prevention of gas hydrates in the drainage line during offshore natural gas hydrate pilot or long-term production.

Spinal cord injury (SCI) causes devastating loss of function and neuronal death without effective treatment. (−)-Epigallocatechin-3-gallate (EGCG) has antioxidant properties and plays an essential role in the nervous system. However, the underlying mechanism by which EGCG promotes neuronal survival and functional recovery in complete spinal cord transection (ST) remains unclear.

Objectives: Facial nerve aberration is the most troublesome situation in congenital malformations of middle ear. The aim of our study is to investigate its imaging and clinical features as well as relevant choice of surgical techniques for hearing improvement. Methods: A retrospective study involving review of clinical data of 227 patients (256 ears) with congenital middle ear anomaly was undertaken, including preoperative computed tomography (CT) data, surgical records and videos. Results: Aberration involving intratemporal facial nerve was found in 82/256 ears (32.03%) with congenital middle ear anomaly. The most common forms of aberration included overhanging over the oval window (50/82 ears, 60.98%), bifurcation (3/82 ears, 3.66%) and transverse over the promontory (3/82 ears, 3.66%), counting for 68.29% (56/82) of the cases with facial nerve aberration. Concomitant stapes malformation was found in 76/82 ears (92.68%) and atresia or stenosis of the oval window in 27/82 ears (32.93%). In 9/82 ears (10.98%) both stapes and oval window was absent. Elective surgeries for the purpose of hearing improvement included stapodotomy + piston implantation, labyrinthotomy, labyrinthotomy + total ossicular replacement prosthesis (TORP) implantation and Vibrant Soundbridge (VSB) implantation. Conclusion: The majority of facial nerve aberration in congenital malformation of middle ear involves displacement of facial nerve, in addition to concomitant malformations of the stapes and/or oval window, which may influence the choice of surgery for hearing improvement. VSB implantation may be considered as a useful option. Keywords: Congenital middle ear anomaly, Facial nerve, Stapes, Oval window, Vibrant Soundbridge (VSB)

Abstract A facile one-step hydrothermal reaction was employed to synthesis an integrated bifunctional composite composed by a network structure of ZnS/ZnO/Ni(OH)2 nanosheets with ZnS/ZnO nanospheres in situ growing on Ni foam. The synergistic effect of these three substances make the composite having both improved electrochemical performances and photocatalytic activity. The ZnS/ZnO/Ni(OH)2-4mmol shows a high specific capacitance of 1173.8 F g−1 at 1 A g−1, as well as good rate capability and relatively stable cyclability. Using as photocatalyst, the methyl orange dye in solution can be completely decomposed under ultraviolet-visible radiation in about 80 min. And the composite is easy to be repeatedly used because bulk Ni foam was used as a carrier. Such a bifunctional composite material provides a new insight for energy storage and utilization as well as the water pollution treatment.

Surface electromyography (sEMG), as a key technology of non-invasive muscle computer interface, is an important method of human-computer interaction. We proposed a CNN-IndRNN (Convolutional Neural Network-Independent Recurrent Neural Network) hybrid algorithm to analyse sEMG signals and classify hand gestures. Ninapro’s dataset of 10 volunteers was used to develop the model, and by using only one time-domain feature (root mean square of sEMG), an average accuracy of 87.43% on 18 gestures is achieved. The proposed algorithm obtains a state-of-the-art classification performance with a significantly reduced model. In order to verify the robustness of the CNN-IndRNN model, a compact real¬time recognition system was constructed. The system was based on open-source hardware (OpenBCI) and a custom Python-based software. Results show that the 10-subject rock-paper-scissors gesture recognition accuracy reaches 99.1%.

Objective(s):Our recent report indicates that breviscapine play a protective role of the kidney by down-regulating transforming growth factor-β1(TGF-β1), α-smooth muscle actin (α-SMA) and alleviating interstitial fibrosis following unilateral ureteral obstruction (UUO). In this study, we investigate the effect of breviscapine on changes of renal water and sodium transport proteins in response to UUO. Materials and Methods: Male Sprague-Dawley rats were divided into 3 groups, sham group, UUO group and UUO treat with breviscapine. After 4, 7 and 14 days, histologic changes and interstitial collagen were determined microscopically following hematoxylin and eosin (H&E) and Masson's trichrome staining. The expression of Aquaporins (AQP-2) and γ-epithelial sodium channel (γ-ENaC) were investigated using immunohistochemistry and Western blot in each group. Results:Breviscapine treatment decrease the tubular injury index and the degree of interstitial collagen deposition significantly compared with the UUO group (P

The mesh matching method is proposed for clearance error and non point contact problem caused by mesh discretization in the finite element analysis rolling bearing. Firstly,the mesh matching and the importance of the matching to contact calculation in finite element analysis is expounded. Secondly,the mesh matched 3- D model of ball bearing is analyzed. Finally,the mesh matching and compacting is analyzed quantificationally based on a simplified model of bearing contact problems. The results show that,the mesh non-matching causes larger error for arcs and cambered surfaces contact problem,the effect of mesh matching is obvious; the mesh matching and compacting can significantly improve the accuracy of analysis for Hertz contact problem; a better analysis precision can be achieved when the mesh matched and non- compacted rolling bearing model is used. The study has a certain guiding significance for accurate finite element modeling and analysis of rolling bearing.