The association between the baseline bone resorption marker CTX and incident dysglycemia after 4 years

Bone is an endocrine organ involved in modulating glucose homeostasis. The role of the bone formation marker osteocalcin （OCN） in predicting diabetes was reported, but with conflicting results. No study has explored the association between baseline bone resorption activity and incident diabetes or prediabetes during follow-up. Our objective was to examine the relationship between the baseline bone resorption marker crosslinked C-telopeptide of type I collagen （CTX） and glycemic dysregulation after 4 years. This longitudinal study was conducted in a university teaching hospital. A total of 195 normal glucose tolerant （NGT） women at baseline were invited for follow-up. The incidence of diabetes and prediabetes （collectively defined as dysglycemia） was recorded. A total of 128 individuals completed the 4-year study. The overall conversion rate from NGT to dysglycemia was 31.3%. The incidence of dysglycemia was lowest in the middle tertile [16.3% （95% confidence interval （CI）, 6.8%-30.70/0）] compared with the lower [31.0% （95% CI, 17.2%-46.1%）] and upper [46.5% （95% CI, 31.2%-62.6%）] tertiles of CTX, with a significant difference seen between the middle and upper tertiles （P = 0.002 5）. After adjusting for multiple confounding variables, the upper tertile of baseline CTX was associated with an increased risk of incident dysglycemia, with an odds ratio of 7.09 （95% CI, 1.73-28.99） when the middle tertile was the reference. Osteoclasts actively regulate glucose homeostasis in a biphasic model that moderately enhanced bone resorption marker CTX at baseline provides protective effects against the deterioration of glucose metabolism, whereas an overactive osteoclastic function contributes to an increased risk of subsequent dysglycemia.

A new fast heat treatment process for cast A356 alloy motorcycle wheel hubs

The normal T6 heat treatment process for cast A356 alloy generally requires about 15 h. This longperiod procedure increases greatly the manufacturing cost and decreases the productivity in practical production. In this study, a new short-time heat treatment process with only 30 min solution time at 540℃ was developed for the production of motorcycle wheel hubs in order to reduce heat treatment time. Comparisons on microstructure evaluation and mechanical properties, such as tensile strength and ductility, were made between this new fast process and the conventional T6 heat treatment. The results revealed that this new heat treatment process enabled the spheroidization of the eutectic silicon thoroughly, while minimizing the growth of eutectic silicon. The A356 alloy after this new short-time heat treatment shows nearly equal mechanical properties compared with the same alloy heat treated in a normal T6 heat treatment. This investigation makes it possible to significantly improve the efficiency of heat treatment on A356 alloy and, at the same time, improve the mechanical properties of the alloy.

A Comparison Study of Deep Galerkin Method and Deep Ritz Method for Elliptic Problems with Different Boundary Conditions

Recent years have witnessed growing interests in solving partial differential equations by deep neural networks,especially in the high-dimensional case.Unlike classical numerical methods,such as finite difference method and finite element method,the enforcement of boundary conditions in deep neural networks is highly nontrivial.One general strategy is to use the penalty method.In the work,we conduct a comparison study for elliptic problems with four different boundary conditions,i.e.,Dirichlet,Neumann,Robin,and periodic boundary conditions,using two representative methods:deep Galerkin method and deep Ritz method.In the former,the PDE residual is minimized in the least-squares sense while the corresponding variational problem is minimized in the latter.Therefore,it is reasonably expected that deep Galerkin method works better for smooth solutions while deep Ritz method works better for low-regularity solutions.However,by a number of examples,we observe that deep Ritz method can outperform deep Galerkin method with a clear dependence of dimensionality even for smooth solutions and deep Galerkin method can also outperform deep Ritz method for low-regularity solutions.Besides,in some cases,when the boundary condition can be implemented in an exact manner,we find that such a strategy not only provides a better approximate solution but also facilitates the training process.

Prognostic impact of number of examined lymph nodes on survival of patients with appendiceal neuroendocrine tumors

BACKGROUND The prognosis of patients with appendiceal neuroendocrine tumors(ANETs) is related to lymph node(LN) metastasis and other factors.However,it is unclear how the number of examined LNs(ELNs) impact on survival.AIM To determine the factors affecting the cancer-specific survival(CSS) of patients with ANET and to evaluate the impact of the number of ELNs on survival.METHODS A total of 4583 ANET patients were analyzed in the Surveillance,Epidemiology,and End Results database.Univariate survival analysis was used to identify factors related to survival and the optimal number of ELNs and lymph node ratio(LNR) were determined by the Kaplan–Meier method.The survival difference was determined by CSS.RESULTS Except for sex,the other factors,such as age,year,race,grade,histological type,stage,tumor size,ELNs,LNR,and surgery type,were associated with prognosis.The 3-,5-,and 10-year CSS rates of ANET patients were 91.2%,87.5,and 81.7%,respectively(median follow-up period of 31 mo and range of 0-499 mo).There was no survival difference between the two surgery types,namely,local resection and colectomy or greater,in both stratifications of tumor size ≥ 2 cm(P = 0.523)and < 2 cm(P = 0.068).In contrast to patients with a tumor size < 2 cm,those with a tumor size ≥ 2 cm were more likely to have LN metastasis(χ~2 = 378.16,P < 0.001).The optimal number of ELNs was more than 11,7,and 18 for all patients,nodenegative patients,and node-positive patients,respectively.CSS rates of patients with a larger number of ELNs were significantly improved(≤ 10 vs ≥ 11,χ~2 =20.303,P < 0.001;≤ 6 vs ≥ 7,χ~2 = 11.569,P < 0.001;≤ 17 vs ≥ 18,χ~2 = 21.990,P < 0.001;respectively).ANET patients with an LNR value ≤ 0.16 were more likely to have better survival than those with values of 0.17-0.48(χ~2 = 48.243,P < 0.001) and 0.49-1(χ~2 = 168.485,P < 0.001).CONCLUSION ANET ≥ 2 cm are more likely to develop LN metastasis.At least 11 ELNs are required to better evaluate the prognosis.For patients with positive LN metastasis,18 or more LNs need to be detected and lower LNR values(LNR ≤ 0.16) indicate a better survival prognosis.

A statistical sensing method by utilizing Wi-Fi CSI subcarriers:Empirical study and performance enhancement

In modern Wi-Fi systems,channel state information(CSI)serves as a foundational support for various sensing applications.Currently,existing CSI-based techniques exhibit limitations in terms of environmental adaptability.As such,optimizing the utilization of subcarrier CSI stands as a critical avenue for enhancing sensing performance.Within the OFDM communication framework,this work derives sensing outcomes for both detection and estimation by harnessing the CSI from every individual measured subcarrier,subsequently consolidating these outcomes.When contrasted against results derived from CSI based on specific extraction protocols or those obtained through weighted summation,the methodology introduced in this study offers substantial improvements in CSI-based detection and estimation performance.This approach not only underscores the significance but also serves as a robust exemplar for the comprehensive application of CSI.

p53 upregulated by HIF-la promotes hypoxiainduced G2/M arrest and renal fibrosis in vitro and in vivo

Hypoxia plays an important role in the genesis and progression of renal fibrosis.The underlying mechanisms, however, have not been sufficiently elucidated. We examined the role of p53 in hypoxia-induced renal fibrosis in cell culture (human and rat renal tubular epithelial cells) and a mouse unilateral ureteral obstruction (UUO) model. Cell cycle of tubular cells was determined by flow cytometry, and the expression of profibrogenic factors was determined by RT-PCR, immunohistochemistry, and western blotting. Chromatin immunoprecipitation and luciferase reporter experiments were performed to explore the effect of HIF-lα on p53 expression. We showed that, in hypoxic tubular cells, p53 upregulation suppressed the expression of CDK1 and cyclins Bl and DI, leading to cell cycle (G2/M) arrest (or delay) and higher expression of TGF-β, CTGF, collagens, and fibronectin. p53 suppression by siRNA or by a specific p53 inhibitor (PIF-α) triggered opposite effects preventing the G2/M arrest and profibrotic changes. In vivo experiments in the UUO model revealed similar antifibrotic results following intraperitoneal administration of PIF-α(2.2 mg/kg). Using gain-of-function, loss-of-function, and luciferase assays, we further identified an HRE3 region on the p53 promoter as the HIF-lα-binding site. The HIF-la-HRE3 binding resulted in a sharp transcriptional activation of p53. Collectively, we show the presence of a hypoxia-activated, p53-responsive profibrogenic pathway in the kidney. During hypoxia, p53 upregulation induced by HIF-la suppresses cell cycle progression, leading to the accumulation of G2/M cells, and activates profibrotic TGF-β and CTGF-mediated signaling pathways, causing extracellular matrix production and renal fibrosis.

Serum uric acid and risk of incident diabetes in middle-aged and elderly Chinese adults: prospective cohort study

The association between serum uric acid and the risk of incident diabetes in Chinese adults remains unknown.This study aimed to investigate this association in a community-dwelling population aged≥40 years in Shanghai,China.Oral glucose tole3rance test was conducted during baseline and follow-up visits.Relative risk regression was utilized to examine the associations between baseline gender-specific serum uric acid levels and incident diabetes risk.A total of 613(10.3%)incident diabetes cases were identified during the follow-up visit after 4.5 years.Fasting plasma glucose,postload glucose,and glycated hemoglobin A1c during the follow-up visit progressively increased across the sex-specific quartiles of serum uric acid(all Ps<0.05).The incidence rate of diabetes increased across the quartiles of serum uric acid(7.43%,8.77%,11.47%,and 13.43%).Multivariate adjusted regression analysis revealed that individuals in the highest quartile had 1.36-fold increased risk of diabetes compared with those in the lowest quartile of serum uric acid(odds ratio(95%confidence interval)=1.36(1.06−1.73)).Stratified analysis indicated that the association was only observed in women.Accordingly,serum uric acid was associated with the increased risk of incident diabetes among middle-aged and elderly Chinese women.

Decreasing intraocular pressure significantly improves retinal vessel density,cytoarchitecture and visual function in rodent oxygen induced retinopathy

We attempted to explore a noninvasive,easily applicable and economically affordable therapy for retinopathy of prematurity(ROP).Rat pups were raised in 80%oxygen from postnatal day 7 to P12,and returned to room air.Travoprost eye drops were administered twice a day for 7 days,to reduce intraocular pressure(IOP)by about 20%.Immunohistochemical staining was performed to visualize vessel endothelial cells,to analyze retinal neurons and cytoarchitecture.Behavioral experiments were carried out to test visual acuity and contrast sensitivity.At the end of the 7-day treatment,the number of vessels extending to the vitreous body was significantly reduced and retinal vessel density increased.This improvement was maintained to the end of the12 th week.In the central retina of the model group,the horizontal cells were completely wiped out,the outer plexiform layer was undetectable,and the rod bipolar cell dendrites sprouted into the outer nuclear layer.The treatment partially reverted these architectural changes.Most importantly,behavioral experiments revealed significantly improved visual acuity and contrast sensitivity in the treated group.Therefore,reducing IOP could potentially serve as a safe and economical measure to treat ROP.

Heterologous biosynthesis of medicarpin using engineered Saccharomyces cerevisiae

Medicarpin is an important bioactive compound with multiple medicinal activities,including anti-tumor,anti-osteoporosis,and anti-bacterial effects.Medicarpin is associated with pterocarpans derived from medicinal plants,such as Sophora japonica,Glycyrrhiza uralensis Fisch.,and Glycyrrhiza glabra L.However,these medicinal plants contain only low amounts of medicarpin.Moreover,the planting area for medicarpin-producing plants is limited;consequently,the current medicarpin supply cannot meet the high demands of medicinal markets.In this study,eight key genes involved in medicarpin biosynthesis were identified using comparative transcriptome and bioinformatic analyses.In vitro and in vivo enzymatic reaction confirmed the catalytic functions of candidate enzymes responsible for the biosynthesis of medicarpin and medicarpin intermediates.Further engineering of these genes in Saccharomyces cerevisiae achieved the heterologous biosynthesis of medicarpin using liquiritigenin as a substrate,with a final medicarpin yield of 0.82±0.18 mg/L.By increasing the gene copy numbers of vestitone reductase(VR)and pterocarpan synthase(PTS),the final medicarpin yield was increased to 2.05±0.72 mg/L.This study provides a solid foundation for the economic and sustainable production of medicarpin through a synthetic biology strategy.

A Second-Order Semi-Implicit Method for the Inertial Landau-Lifshitz-Gilbert Equation

Electron spins in magnetic materials have preferred orientations collectively and generate the macroscopic magnetization.Its dynamics spans over a wide range of timescales from femtosecond to picosecond,and then to nanosecond.The Landau-Lifshitz-Gilbert(LLG)equation has been widely used in micromagnetics simulations over decades.Recent theoretical and experimental advances have shown that the inertia of magnetization emerges at sub-picosecond timescales and contributes significantly to the ultrafast magnetization dynamics,which cannot be captured intrinsically by the LLG equation.Therefore,as a generalization,the inertial LLG(iLLG)equation is proposed to model the ultrafast magnetization dynamics.Mathematically,the LLG equation is a nonlinear system of parabolic type with(possible)degeneracy.However,the iLLG equation is a nonlinear system of mixed hyperbolic-parabolic type with degeneracy,and exhibits more complicated structures.It behaves as a hyperbolic system at sub-picosecond timescales,while behaves as a parabolic system at larger timescales spanning from picosecond to nanosecond.Such hybrid behaviors impose additional difficulties on designing efficient numerical methods for the iLLG equation.In this work,we propose a second-order semiimplicit scheme to solve the iLLG equation.The second-order temporal derivative of magnetization is approximated by the standard centered difference scheme,and the first-order temporal derivative is approximated by the midpoint scheme involving three time steps.The nonlinear terms are treated semi-implicitly using one-sided interpolation with second-order accuracy.At each time step,the unconditionally unique solvability of the unsymmetric linear system is proved with detailed discussions on the condition number.Numerically,the second-order accuracy of the proposed method in both time and space is verified.At sub-picosecond timescales,the inertial effect of ferromagnetics is observed in micromagnetics simulations,in consistency with the hyperbolic property of the iLLG model;at nanosecond timescales,the results of the iLLG model are in nice agreements with those of the LLG model,in consistency with the parabolic feature of the iLLG model.

冲绳海槽热液区可培养硫氧化细菌多样性及其硫氧化特性

冲绳海槽热液区独特的地质环境孕育了特殊的生物群落,硫氧化细菌作为生物地球化学循环的重要参与者在热液生态系统中发挥着至关重要的作用。【目的】通过硫氧化菌株的分离培养揭示冲绳海槽热液区可培养硫氧化细菌的多样性和硫氧化活性。【方法】采用多种培养基对冲绳海槽热液区不同沉积物样品中的硫氧化细菌进行富集培养和分离纯化;利用16S rRNA基因序列确定硫氧化细菌的分类地位并进行系统发育分析;采用碘量法对典型硫氧化菌株硫氧化活性进行检测。【结果】本研究从冲绳海槽热液区样品中共分离鉴定85株硫氧化细菌,分属于α-变形菌纲、γ-变形菌纲、放线菌门和厚壁菌门,优势属为氢弧菌属(Hydrogenovibrio)、拉布伦氏菌属(Labrenzia)、深海海旋菌属(Thalassospira)和海杆状菌属(Marinobacter)。硫氧化活性检测结果表明,7株典型硫氧化菌株对硫代硫酸钠的降解活性介于31%–100%之间,其中泰坦尼克号盐单胞菌SOB56 (Halomonas titanicae SOB56)、南极海杆状菌SOB93(Marinobacter antarcticus SOB93)、印度硫氧化粗杆菌SOB107 (Thioclava indica SOB107)和嗜温氢弧菌CJG136 (Hydrogenovibrio thermophiles CJG136)可以完全降解硫代硫酸钠。【结论】冲绳海槽热液区可培养硫氧化细菌的多样性丰富,为研究该热液区的硫循环过程提供了实验材料和理论基础,多种硫氧化活性菌株的获得极大地丰富了菌种资源,为探究深海热液区硫循环的能量代谢途径和分子机制奠定基础。

BDNF improves axon transportation and rescues visual function in a rodent model of acute elevation of intraocular pressure

Optic neuropathies lead to blindness;the common pathology is the degeneration of axons of the retinal ganglion cells. In this study, we used a rat model of retinal ischemia-reperfusion and a one-time intravitreal brain-derived neurotrophic factor(BDNF)injection;then we examined axon transportation function, continuity, physical presence of axons in different part of the optic nerve, and the expression level of proteins involved in axon transportation. We found that in the disease model, axon transportation was the most severely affected, followed by axon continuity, then the number of axons in the distal and proximal optic nerve. BDNF treatment relieved all reductions and significantly restored function. The molecular changes were more minor,probably due to massive gliosis of the optic nerve, so interpretation of protein expression data should be done with some caution.The process in this acute model resembles a fast-forward of changes in the chronic model of glaucoma. Therefore, impairment in axon transportation appears to be a common early process underlying different optic neuropathies. This research on effective intervention can be used to develop interventions for all optic neuropathies targeting axon transportation.

Two-Level Additive Schwarz Methods Using Rough Polyharmonic Splines-Based Coarse Spaces

This paper introduces a domain decomposition preconditioner for elliptic equations with rough coefficients. The coarse space of the domain decomposition method is constructed via the so-called rough polyharmonic splines(RPS for short). As an approximation space of the elliptic problem, RPS is known to recover the quasi-optimal convergence rate and attain the quasi-optimal localization property. The authors lay out the formulation of the RPS based domain decomposition preconditioner, and numerically verify the performance boost of this method through several examples.

Lattice Boltzmann Model for Time-Fractional NonlinearWave Equations

In this paper,a lattice Boltzmann model with BGK operator(LBGK)for solving time-fractional nonlinear wave equations in Caputo sense is proposed.First,the Caputo fractional derivative is approximated using the fast evolution algorithm based on the sum-of-exponentials approximation.Then the target equation is transformed into an approximate form,and for which a LBGK model is developed.Through the Chapman-Enskog analysis,the macroscopic equation can be recovered from the present LBGK model.In addition,the proposed model can be extended to solve the time-fractional Klein-Gordon equation and the time-fractional Sine-Gordon equation.Finally,several numerical examples are performed to show the accuracy and efficiency of the present LBGK model.From the numerical results,the present model has a second-order accuracy in space.

Empathic Contagious Pain and Consolation in Laboratory Rodents:Species and Sex Comparisons

Dear Editor,In the past five years,we have developed a behavioral model of empathy for pain in rats[1-5].Experimentally,at least two types of behaviors associated with empathy for pain in rats can be identified,based on the evolutionary notion of the Russian doll model[6].One has been referred to as an observer's empathic consolation,which is driven by social interaction with a demonstrator in pain[3,7-9];the other is referred to as observational contagious pain(OCP or empathic transfer of pain)from a distressed object to a witnessing subject[1-3,5].

Image-Forming Visual Basis of Empathy for Pain in Mice

Dear Editor.Empathy for distress refers to the highly evolutionarilyconserved ability of humans and other social animals to feel,recognize,and understand others’painful conditions(pain,fear,and catastrophe)[1,2]and even benefit others by releasing distress through sharing,caring,and cooperation[1].In the past decade,several types of lower empathic response have been gradually identified and characterized in laboratory rodents(rats and mice),referred to as empathic contagious pain[3-5],observational fear learning[2],and contagious itch[6].