Model informed precision medicine of Chinese herbal medicines formulas-A multi-scale mechanistic intelligent model

Recent trends suggest that Chinese herbal medicine formulas(CHM formulas)are promising treatments for complex diseases.To characterize the precise syndromes,precise diseases and precise targets of the precise targets between complex diseases and CHM formulas,we developed an artificial intelligence-based quantitative predictive algorithm(DeepTCM).DeepTCM has gone through multilevel model calibration and validation against a comprehensive set of herb and disease data so that it accurately captures the complex cellular signaling,molecular and theoretical levels of traditional Chinese medicine(TCM).As an example,our model simulated the optimal CHM formulas for the treatment of coronary heart disease(CHD)with depression,and through model sensitivity analysis,we calculated the balanced scoring of the formulas.Furthermore,we constructed a biological knowledge graph representing interactions by associating herb-target and gene-disease interactions.Finally,we experimentally confirmed the therapeutic effect and pharmacological mechanism of a novel model-predicted intervention in humans and mice.This novel multiscale model opened up a new avenue to combine“disease syndrome”and“macro micro”system modeling to facilitate translational research in CHM formulas.

高旋二维弹道修正弹的角运动特性

为研究高旋二维弹道修正弹舵控后的攻角与速度偏角的特性,通过在无控弹角运动基础上增加控制组件提供的控制力和力矩,建立了其角运动方程,对起始扰动作用、瞬时控制力作用、长时间控制力作用下的弹丸攻角、速度偏角规律进行了分析。数值计算结果表明:高旋二维弹道修正弹受瞬时控制力作用时,产生的平衡攻角、平均速度偏角的方向与瞬时控制力方向大致相反;在固定方位舵控力长时间作用下,平衡攻角、平均速度偏角方向与控制力方向近似成180°,相差一个小的角度;攻角运动是由舵控力产生相反方向的攻角与重力产生向右的动力平衡角合成的,该攻角运动规律将影响弹道的质心运动。研究结果为高旋二维弹道修正弹的控制策略与控制方案设计提供了理论依据与参考。

Diamonds, Super-Reduced and Crustal Minerals in Chromitites of the Hegenshan and Sartohay Ophiolites, Central Asian Orogenic Belt, China

The Central Asian Orogenic Belt(CAOB)is a huge tectonic mélange that lies between the North China Craton and the Siberian Block.It is composed of multiple orogenic belts,continental fragments,magmatic and metamorphic rocks,suture zones and discontinuous ophiolite belts.Although the Hegenshan and Sartohay ophiolites are separated by nearly 3000 km and lie in completely different parts of the CAOB,they are remarkably similar in many respects.Both are composed mainly of serpentinized peridotite and dunite,with minor gabbro and sparse basalt.They both host significant podiform chromitites that consist of high-Al,refractory magnesiochromite with Cr#s[100Cr/(Cr+Al)]averaging<60.The Sartohay ophiolite has a zircon U-Pb age of ca.300 Ma and has been intruded by granitic plutons of similar age,resulting in intense hydrothermal activity and the formation of gold-bearing listwanites.The age of the Hegenshan is not firmly established but is thought to have formed in the Carboniferous.Like many other ophiolites that we have investigated in other orogenic belts,the chromitites in these two bodieshave abundant diamonds,as well as numerous super-reduced and crustal minerals.The diamonds are mostly,colorless to pale yellow,200-300μm across and have euhedral to anhedral shapes.They all have low carbon isotopes(δ14C=-18 to-29)and some have visible inclusions.These are accompanied by numerous super-reduced minerals such as moissanite,native elements(Fe,Cr,Si,Al,Mn),and alloys(e.g.,Ni-Mn-Fe,Ni-Fe-Al,Ni-Mn-Co,Cr-Ni-Fe,Cr-Fe,Cr-Fe-Mn),as well as a wide range of oxides,sulfides and silicates.Grains of zircon are abundant in the chromitites of both ophiolites and range in age from Precambrian to Cretaceous,reflecting both incorporation of old zircons and modification of grains by hydrothermal alteration.Our investigation confirms that high-Al,refractory chromitites in these two ophiolites have the same range of exotic minerals as high-Cr metallurgical chromitites such as those in the Luobusa ophiolite of Tibet.These collections of exotic minerals in ophiolitic chromitites indicate complex,multi-stage recycling of oceanic and continental crustal material at least to the mantle transition zone,followed by uprise and emplacement of the peridotites into relatively shallow ophiolites.

Evaluation on Potential Ecological Risk of Heavy Metals in Soil from Penglai Fairyland Park

This study aims at evaluating the heavy metals pollution in soil collected from Penglai Fairyland Park in Guiyang,and predicting the harm of heavy metals to human health. Based on the background value of soil in Guizhou and Soil Environment Quality Standard( GB15618-1995),by using the geoaccumulation index method and Hakanson potential ecological risk assessment method,we research pollution characteristics and ecological risk of heavy metals in soil from the study area. The results show that from the index of geoaccumulation,the pollution level of heavy metals in agricultural soil from Penglai Fairyland Park is in the order of Ni > Cu > Hg > Cd > As > Zn > Cr > Pb. From the potential ecological harm index evaluation,soil is at slight ecological risk level in the park and the potential ecological hazard degree is in the order of Hg > Cd > Ni > As > Cu > Cr > Pb > Zn. The soil ecological environment in research area is only mildly damaged. Thus,the soil in research area is at the level of security,and it is suitable for cultivation of crops and less harmful to human health.

Prevalence and serotype distribution of nasopharyngeal carriage of Streptococcus pneumoniae among healthy children under 5 years of age in Hainan Province, China

Background The thirteen-valent pneumococcal conjugate vaccine(PCV13)is not included in the national immu-nization program and is administered voluntarily with informed consent in China.In preparation for assessing the impact of pilot introduction in Hainan Province,we conducted a carriage study among children under 5 years of age from four locations in Hainan Province,China.Methods From March to June 2022,nasopharyngeal(NP)swabs,collected from healthy children aged younger than 59 months who lived in the 4 different locations(Haikou,Wanning,Baisha and Qiongzhong)in Hainan Province,were tested for pneumococcus using conventional culture.Pneumococcal isolates were serotyped using the Quel-lung reaction.Risk factors associated with pneumococcal colonization were assessed using univariate analysis and multivariable logistic regression adjusting for age,daycare attendance and other factors.Results Pneumococcus was isolated in 710(30.4%)of the 2333 children enrolled.Of 737 pneumococci,29 serotypes were identifed;60.9%were PCV13 serotypes;the most common vaccine serotypes were 6B(20.4%),19F(13.0%),6A(11.9%)and 23F(6.1%);and the most common nonvaccine serotypes were 23A(12.9%),34(6.1%)and nontypeable(NT)pneumococci(5.6%).Children vaccinated with PCV13 had lower carriage(17.7%vs 32.5%;P=0.0001)and fewer PCV13 serotypes(41.9%vs 62.7%;P=0.0017)compared to unimmunized children.After adjustment,NP carriage Was higher among children attending daycare(aOR=2.3,95%CI:1.7-3.2),living in rural areas(aOR=1.4,95%CI:1.1-1.8),living with siblings(aOR=1.3,95%CI:1.0-1.6)and whose mothers had completed senior high/technical sec-ondary school(aOR=1.5,95%CI:1.1-2.0).In contrast,completion of 3-4 doses of PCV13 were associated with a lower carriage rate(aOR=0.6,95%CI:0.4-0.9).Conclusions We established the baseline of pneumococcal carriage,serotype distribution and PCV13 immuni-zation rates among healthy children under 5 years of age in Hainan Province,prior to the introduction of PCV13 into the national immunization program.The high proportion of PCV13 serotypes suggests that PCV13 introduction will likely have a substantial impact on pneumococcal carriage in Hainan Province.

A Low-carbon Operation Optimization Method of ETG-RIES Based on Adaptive Optimization Spiking Neural P Systems

To enhance multi-energy complementarity and foster a low carbon economy of energy resources,this paper proposes an innovative low-carbon operation opti-mization method for electric-thermal-gas regional inte-grated energy systems.To bolster the low-carbon operation capabilities of such systems,a coordinated operation framework is presented that integrates carbon capture devices,power to gas equipment,combined heat and power units,and a multi-energy storage system.To address the challenge of high-dimensional constraint imbalance in the optimization process,a novel low-carbon operation opti-mization method is then proposed.The new method is based on an adaptive single-objective continuous optimiza-tion spiking neural P system,specifically designed for this purpose.Furthermore,simulation models of four typical schemes are established and employed to test and analyze the economy and carbon environmental pollution degree of the proposed system model,as well as the performance of the operation optimization method.Finally,simulation results show that the proposed method not only considers the economic viability of the target integrated energy sys-tem,but also significantly improves the wind power utilization and carbon reduction capabilities.

金融结构与环境污染:新结构环境金融的理论初探

基于新结构经济学视角,本文初步构建了一个金融结构与环境污染的发展、转型与运行的分析框架。研究认为,在发展层面,金融发展在不同的经济发展阶段对环境污染的影响不同,遵循环境库兹涅茨曲线机制。在运行层面,金融结构与发展阶段所对应的要素禀赋结构和产业技术结构的匹配程度越高,越有利于减少环境污染;相反,若金融结构偏离发展阶段所决定的最优金融结构,则扭曲的金融结构将加剧环境污染。在转型层面,政府发展战略是影响金融结构的重要因素,若发展战略违背比较优势,则会导致金融结构扭曲,进而加剧污染。

Puerarin, an isoflavone compound extracted from Gegen (Radix Puerariae Lobatae), modulates sclera remodeling caused by extremely low frequency electromagnetic fields

OBJECTIVE: To evaluate the protective effect of puerarin [an isoflavone compound extracted from Gegen(Radix Puerariae Lobatae)] in scleral remodeling induced by extremely low frequency electromagnetic fields(ELF-EMFs).METHODS: Human fetal scleral fibroblasts(HFSFs)were divided into 5 groups:(a) untreated controls;(b) cells treated with ELF-EMFs;(c) cells treated with ELF-EMFs and puerarin 0.1 μM;(d) cells treated with ELF-EMFs and puerarin 1 μM;(e) cells treated with ELF-EMFs and puerarin 10 μM. Cell proliferation activity was measured by the cell-counting kit-8 assay. Matrix metalloproteinase-2(MMP-2) activity was measured by gelatin enzymography.MMP-2 and collagenⅠ(COL1A1) m RNA, protein expression were measured by Real-Time polymerase chain reaction, Western blot analysis, respectively.RESULTS: Puerarin reduced the inhibition in cell proliferation, MMP-2 activity, m RNA, protein expression of HFSFs exposed to ELF-EMFs and enhanced the COL1A1 m RNA and protein expression.CONCLUSION: Puerarin was found to participate in the matrix remodeling process. It might be a potential agent for the treatment of extracellular matrix degradation of sclera associated with ocular conditions.

Controversial opinion:evaluation of EGR1 and LAMA2 loci for high myopia in Chinese populations

Functional studies have suggested the important role of early growth response I （EGR1） and Laminin a2- chain （LAMA,？.） in human eye development. Genetic studies have reported a significant association of the single nu- cleotide polymorphism （SNP） in the LAMA2 gene with myopia. This study aimed to evaluate the association of the tagging SNPs （tSNPs） in the EGR1 and LAMA2 genes with high myopia in two independent Han Chinese populations. Four tSNPs （rs11743810 in the EGR1 gene; rs2571575, rs9321170, and rs1889891 in the LAMA2 gene） were se- lected, according to the HapMap database （http：//hapmap.ncbi.nlm.nih.gov）, and were genotyped using the ligase detection reaction （LDR） approach for 167 Hart Chinese nuclear families with extremely highly myopic offspring （〈-10.0 diopters） and an independent group with 485 extremely highly myopic cases （〈-10.0 diopters） and 499 con- trois. Direct sequencing was used to confirm the LDR results in twenty randomly selected subjects. Family-based association analysis was performed using the family-based association test （FBAT） software package （Version 1.5.5）. Population-based association analysis was performed using the Chi-square test. The association analysis power was estimated using online software （http：lldesign.cs.ucla.edu）. The FBAT demonstrated that all four tSNPs tested did not show association with high myopia （P〉0.05）. Haplotype analysis of tSNPs in the LAMA2 genes also did not show a significant association （P〉0.05）. Meanwhile, population-based association analysis also showed no significant asso- ciation results with high myopia （P〉0.05）. On the basis of our family- and population-based analyses for the Han Chinese population, we did not find positive association signals of the four SNPs in the LAMA2 and EGR1 genes with high myopia.

The deubiquitinating gene Usp29 is dispensable for fertility in male mice

The balanced actions between ubiquitination and deubiquitination precisely control the levels of various proteins vital for spermatogenesis. Ubiquitin-specific processing proteases(USPs) are the largest family of deubiquitinatingenzymes(DUBs),containing more than 50 members. So far, the functions of only a few USPs in male fertility have been studied, the roles of the majority are yet unknown. The present study aimed to explore the function of Usp29(ubiquitin-specific protease 29) in male fertility. We found that Usp29 showed predominant expression in mouse testis, and its m RNA expression started to increase at 14 days postpartum(dpp), with a peak at 28 and 35 dpp. Using CRISPR/Cas9 technology, we generated Usp29 knockout mice(Usp29^(–/–)). Usp29^(–/–)mice exhibited no overt developmental anomalies. Further examination revealed that Usp29^(–/–)mice had normal fertility and showed no detectable difference in the testis/body weight ratio, testicular and epididymal histology as well as epididymal sperm count from the wild-type littermates. Moreover, Usp29 is not a pseudogene in mice. Taken together, our study first reported that though Usp29 is predominantly expressed in the testis, it is not essential for male fertility in mice.

The prediction of external flow field and hydrodynamic force with limited data using deep neural network

Predicting the external flow field with limited data or limited measurements has attracted long-time interests of researchers in many industrial applications.Physics informed neural network(PINN)provides a seamless framework for combining the measured data with the deep neural network,making the neural network capable of executing certain physical constraints.Unlike the data-driven model to learn the end-to-end mapping between the sensor data and high-dimensional flow field,PINN need no prior high-dimensional field as the training dataset and can construct the mapping from sensor data to high dimensional flow field directly.However,the extrapolation of the flow field in the temporal direction is limited due to the lack of training data.Therefore,we apply the long short-term memory(LSTM)network and physics-informed neural network(PINN)to predict the flow field and hydrodynamic force in the future temporal domain with limited data measured in the spatial domain.The physical constraints(conservation laws of fluid flow,e.g.,Navier-Stokes equations)are embedded into the loss function to enforce the trained neural network to capture some latent physical relation between the output fluid parameters and input tempo-spatial parameters.The sparsely measured points in this work are obtained from computational fluid dynamics(CFD)solver based on the local radial basis function(RBF)method.Different numbers of spatial measured points(4–35)downstream the cylinder are trained with/without the prior knowledge of Reynolds number to validate the availability and accuracy of the proposed approach.More practical applications of flow field prediction can compute the drag and lift force along with the cylinder,while different geometry shapes are taken into account.By comparing the flow field reconstruction and force prediction with CFD results,the proposed approach produces a comparable level of accuracy while significantly fewer data in the spatial domain is needed.The numerical results demonstrate that the proposed approach with a specific deep neural network configuration is of great potential for emerging cases where the measured data are often limited.