Sex Determination in Homo sapiens as a Multi-Step Process: Potential for Development of Variants and Sex Differences in Disease Risk

Reproduction via cis-binary mechanisms appears to have evolved fairly early in the evolution of complex organisms, and a system committed to prior to evolution of humans. While the evolution of a chromosomal-specific approach has been a successful strategy for survival of a large variety of species including humans, the fidelity of sex determination leading to 100% cis-binary outcomes is not achieved in many species, with evidence for homosexual or bisexual behaviour evident in more than 1500 species. Thus, such outcomes indicates that sex determination is a multi-step process and not a single event, and as such, could lead to the appearance of variants during the process which developed much earlier than humans. Variants could arise either due to intrinsic variation in the steps of determination, or also be influenced by environmental factors of a biological or psychological nature. In contrast to homosexual variants which do not require interventions such as hormone therapy or surgery, expression of gender dysphoria, is more based in psychology, but also has biological underpinnings and can be influenced by such hormonal interventions and surgery. While the numbers of those with gender dysphoria is small (~0.6% - 1.0% of population), the attention given to this issue raises the possibility of biological and psychological environmental factors impacting the emergence of some of those expressing gender dysphoria. Furthermore, transitioning from male-to-female or female-to-male can have consequences regarding disease risks latter in life, including the appearance of autoimmune diseases. This review will attempt to review some of the evidence regarding sex determination, discuss why the system has potentially not been improved upon during evolution, how a potential role for sex chromosome function on neurodevelopment may be central to variation in humans, and how commitment to the current strategy is likely integrated into other sex-related events such as puberty, pregnancy, and menopause to ensure species survival. It will also discuss how variants in sex determination could contribute to sex differences in disease risk and how epigenetic modifications could play a role in such risk. .

Silencing transformer and transformer-2 in Zeugodacus cucurbitae causes defective sex determination with inviability of most pseudomales

transformer is a switch gene for sex determination in many insects, which cooperates with transformer-2 that is expressed in both sexes to regulate female differentiation, particularly in dipterans. Zeugodacus cucurbitae(Coquillett) is a very destructive pest worldwide, however, its sex determination pathway remains largely uncharacterized. Here, we show that the female sex ratio is sharply reduced with knockdown of either transformer or transformer-2 by RNA interference in early embryos of Z. cucurbitae. Most of the males grown from the embryos with transient transformer and transformer-2 suppression mated with wild-type females and produced mixed sex progeny, with one exception that produced only female progeny, and all of the few remaining males failed to mate with wild-type females and produced no progeny. The exceptional male and those males with mating failure were XX pseudomales as determined by the detection of Y chromosome-linked Maleness-on-the-Y, indicating that most XX pseudomales are not viable. The phenotypes of transformer and transformer-2 suggest that they play a key role in regulating sex determination and are required for female sexual development of Z. cucurbitae. Our results will be beneficial to the understanding of sex determination in Z. cucurbitae and can facilitate the development of genetic sexing strains for its biological control.

Relative orbit determination algorithm of space targets with passive observation

Angles-only relative orbit determination for space non-cooperative targets based on passive sensor is subject to weakly observable problem of the relative state between two spacecraft. Previously, the evidence for angles-only observability was found by using cylindrical dynamics, however, the solution of orbit determination is still not provided. This study develops a relative orbit determination algorithm with the cylindrical dynamics based on differential evolution. Firstly, the relative motion dynamics and line-of-sight measurement model for nearcircular orbit are established in cylindrical coordinate system.Secondly, the observability is qualitatively analyzed by using the dynamics and measurement model where the unobservable geometry is found. Then, the angles-only relative orbit determination problem is modeled into an optimal searching frame and an improved differential evolution algorithm is introduced to solve the problem. Finally, the proposed algorithm is verified and tested by a set of numerical simulations in the context of highEarth and low-Earth cases. The results show that initial relative orbit determination(IROD) solution with an appropriate accuracy in a relative short span is achieved, which can be used to initialize the navigation filter.

The Impact of Sleep Determination on Procrastination before Bedtime:The Role of Anxiety

Objective:The importance of good sleep for energy recovery and overall physical and mental health cannot be overstated.However,the increasing competitiveness of society,diversifying lifestyles,and the rapid spread of the internet and electronic devices have significantly impacted people’s sleep patterns,particularly through bedtime procrastination.Therefore,this study aims to investigate the relationship and underlying mechanisms between sleep determination,anxiety,and bedtime procrastination among the Chinese population.Method:The study utilized data from a national survey—the China Residents’Sleep Condition Survey(November 2021,with 6,037 participants).By constructing mediation and moderation models,it analyzed the relationship and mechanisms between sleep determination and bedtime procrastination,highlighting the dual role of anxiety:as a mediator between sleep determination and bedtime procrastination,and as a moderator of their relationship.Results:There was a negative correlation between sleep determination and bedtime procrastination;anxiety was related to an increase in bedtime procrastination behaviors;In the interplay between sleep determination and pre-bedtime procrastination,the regulatory effect of anxiety is found to be more pronounced than its intermediary role,with anxiety significantly diminishing the inverse relationship between sleep determination and procrastination before bedtime.Conclusion:Bedtime procrastination can lead to sleep issues,thus reducing sleep quality.Enhancing sleep determination or alleviating pre-sleep anxiety can help inhibit bedtime procrastination behaviors.Intervening and reducing bedtime procrastination is one of the effective measures to improve sleep quality.

Research Progress on Purification Process, Content Determination and Pharmacological Action of Atractylodin

Atractylodis Rhizoma comes from the dry rhizome of Atractylis lancea or Atractylodes chinensis in the Compositae family,and it is suitable for preventing and treating diseases such as cold,edema,night blindness and rheumatic arthralgia.Atractylodin is the main active component extracted and isolated from Atractylodis Rhizoma.A large number of studies have found that atractylodin has excellent drug activity in improving gastrointestinal emptying,anti-inflammation,inhibiting malignant tumor and reducing blood lipid.In this paper,the purification process and pharmacological activity of Atractylodin were summarized to provide a theoretical basis for basic research,clinical application and further development and utilization of atractylodin.

Determination of Chlorogenic Acid,Geniposide,Total Flavonoids and Total Triterpenes in Wulan-13

[Objectives]This study was conducted to establish a method for the determination of chlorogenic acid,geniposide,total flavonoids and total triterpenes in Wulan-13.[Methods]The contents of chlorogenic acid and geniposide were determined by HPLC,and the contents of total flavonoids and total triterpenes were determined by an ultraviolet spectrophotometer.[Results]There was a good linear relation between the mass of chlorogenic acid reference substance and the peak area in the range of 0.05-0.45μg,and the regression equation was Y=2524.1X+3.1943,(r=0.9998).A good linear relationship was found between the mass of gardenoside reference substance and the peak area in the range of 0.776-6.984μg,and the regression equation was Y=1670.5X+64.804,(r=0.9998).There was also a good linear relation between the mass of rutin reference substance and its absorbance in the range of 0.00808-0.04848 mg,and the regression equation was Y=12.916X+0.014,(r=0.999).The mass of oleanolic acid reference substance had a good linear relation with its absorbance in the range of 0.00418-0.0209 mg,and the regression equation was Y=51.89X-0.0839,(r=0.9991).[Conclusions]The content determination method is simple,reliable and reproducible,and suitable for controlling the contents of chlorogenic acid,geniposide,total flavonoids and total triterpenes in Wulan-13.

Overexpression of Kdm6b induces testicular differentiation in a temperature-dependent sex determination system

In reptiles,such as the red-eared slider turtle(Trachemys scripta elegans),gonadal sex determination is highly dependent on the environmental temperature during embryonic stages.This complex process,which leads to differentiation into either testes or ovaries,is governed by the finely tuned expression of upstream genes,notably the testis-promoting gene Dmrt1 and the ovary-promoting gene Foxl2.Recent studies have identified epigenetic regulation as a crucial factor in testis development,with the H3K27me3 demethylase KDM6B being essential for Dmrt1 expression in T.s.elegans.However,whether KDM6B alone can induce testicular differentiation remains unclear.In this study,we found that overexpression of Kdm6b in T.s.elegans embryos induced the male development pathway,accompanied by a rapid increase in the gonadal expression of Dmrt1 at 31°C,a temperature typically resulting in female development.Notably,this sex reversal could be entirely rescued by Dmrt1 knockdown.These findings demonstrate that Kdm6b is sufficient for commitment to the male pathway,underscoring its role as a critical epigenetic regulator in the sex determination of the red-eared slider turtle.

Determination of Benzoylaconitine Compounds in the Decoctions of Aconiti Lateralis Radix Praeparata(Heishun Pieces),Trichosanthis Fructus and Their Combination

[Objectives]This study was conducted to determine the contents of benzoylmesaconine,benzoylaconitine and benzoylhypacoitine in the decoctions of Heishun pieces,Trichosanthis Fructus and their combination.[Methods]Heishun pieces,Trichosanthis Fructus and their combination were extracted for different time periods,and then grouped.HPLC was performed using an Agilent ZORBAX SB-C 18 chromatographic column(4.6 mm×250 mm,5μm)and acetonitrile-0.02 mol/L sodium dihydrogen phosphate as the mobile phase at a flow rate of 1 mL/min and a column temperature of 30℃,and the sample volume was 20μL.The detection wavelength was 230 nm.[Results]The total amounts of benzoylmesaconine,benzoylaconitine and benzoylhypacoitine in the single decoction group of Heishun pieces were all significantly different from those in the combined decoction group at corresponding time.[Conclusions]The total content of the benzoylaconitine type increased significantly after the combined decoction of Heishun pieces and Fructus Trichosanthis,which proves the scientificity of"eighteen incompatible medicaments,19 counteraction"in traditional Chinese medicine to some extent.

TLC Identification of Yao Medicine Pileostegia tomentellal and Extraction Technology and Content Determination of Umbelliferone

[Objectives]To establish a TLC and content determination method of Pileostegia tomentellal,with umbelliferone as the indicator component.[Methods]TLC identification was performed by silica gel G thin layer plate with n-hexane-ethyl acetate(4:3)as the developing agent,and the plate was examined by UV lamp(365 nm).The umbelliferone content was determined by HPLC:Inertsil ODS-3 C 18 column(4.60 mm×250 mm,5μm);mobile phase acetonitrile-0.2%phosphoric acid gradient elution;detection wavelength 320 nm,flow rate 1.0 mL/min,column temperature 30℃,injection volume 10μL.[Results]The chromatogram of P.tomentellal showed the same color spot in the same position as that of reference medicinal material,and the spot was clear with good specificity.Umbelliferone showed a good linear relationship when the injection volume was 2.63-131.27μg/mL(R^(2)=0.9997).The average recovery of umbelliferone in the low,middle and high adding groups of P.tomentellal was 99.57%and the RSD was 2.15%.[Conclusions]The method can effectively identify Yao medicine P.tomentellal and accurately determine the content of umbelliferone in medicinal materials,which will provide a scientific basis for the development and utilization of medicinal resources of Yao medicine P.tomentellal.

Frequentist and Bayesian Sample Size Determination for Single-Arm Clinical Trials Based on a Binary Response Variable: A Shiny App to Implement Exact Methods

Sample size determination typically relies on a power analysis based on a frequentist conditional approach. This latter can be seen as a particular case of the two-priors approach, which allows to build four distinct power functions to select the optimal sample size. We revise this approach when the focus is on testing a single binomial proportion. We consider exact methods and introduce a conservative criterion to account for the typical non-monotonic behavior of the power functions, when dealing with discrete data. The main purpose of this paper is to present a Shiny App providing a user-friendly, interactive tool to apply these criteria. The app also provides specific tools to elicit the analysis and the design prior distributions, which are the core of the two-priors approach.

Field Load Test Based SHM System Safety Standard Determination for Rigid Frame Bridge

The deteriorated continuous rigid frame bridge is strengthened by external prestressing. Static loading tests wereconducted before and after the bridge rehabilitation to verify the effectiveness of the rehabilitation process. Thestiffness of the repaired bridge is improved, and the maximum deflection of the load test is reduced from 37.9 to27.6 mm. A bridge health monitoring system is installed after the bridge is reinforced. To achieve an easy assessmentof the bridge’s safety status by directly using transferred data, a real-time safety warning system is createdbased on a five-level safety standard. The threshold for each safety level will be determined by theoretical calculationsand the outcomes of static loading tests. The highest risk threshold will be set at the ultimate limit statevalue. The remaining levels, namely middle risk, low risk, and very low risk, will be determined usingreduction coefficients of 0.95, 0.9, and 0.8, respectively.

Determination of Salvianolic Acid B in Yiqi Huayu Prescription by HPLC

[Objectives]To determine the content of salvianolic acid B in Yiqi Huayu Prescription by HPLC.[Methods]The chromatographic column was ZORBAX Eclipse Plus C 18(4.6 nm×250 nm,5μm);the mobile phase was acetonitrile-0.1%phosphoric acid(21:79),the detection wavelength was 286 nm,the column temperature was 30℃,and the flow rate was 1.0 mL/min.A method for determination of salvianolic acid B in Yiqi Huayu Prescription was established.[Results]The linear relationship of salvianolic acid B was good in the range of 0.0214-0.4064 mg/mL.The regression equation was Y=5995.98984 X-0.07332,r=0.9999.The average recovery rate was 98.88%(RSD=1.6%).[Conclusions]The method is reliable,accurate and specific,and can be used for the determination of salvianolic acid B in Yiqi Huayu Prescription.

基于区域分解的并行SIMPLER算法研究

在同位网格上建立了基于重叠型区域分解的并行SIMPLER算法,给出了区域划分和数据交换的实施细则.并在集群系统下通过对顶盖驱动方腔流进行模拟验证了算法的可靠性.数值结果表明,加速比成线性增加,随着计算规模的增大,并行效率可达到95%以上.

聚合物熔体双尺度模型和SIMPLER方法在收缩流中的应用

采用宏细观双尺度模型描述了聚合物熔体的流动行为,实现了聚合物熔体宏观流变和细观哑铃大分子尺度间信息的传递。采用基于交错网格的SIMPLER-FDMS对双尺度模型进行求解,成功地计算了粘弹性熔体在4∶1平板收缩流动中的速度、压力以及应力的分布,得到了与实验数据和Renardy理论渐近分析结果相一致的结果。从而说明宏细观双尺度模型和基于交错网格的SIMPLER-FDMS算法在粘弹性熔体流动行为的数值模拟中是合理的和可行的。

基于SIMPLER与PISO的流场改进算法

提出了一种用于求解传热与流动问题的新算法—SIMPLEXT方法。该算法采用SIMPLER算法思想耦合初始压力场和速度场,采用PISO算法策略来实现压力场和速度场同时更好地满足动量方程和连续性方程,且兼顾考虑邻点速度修正值对所计算点速度修正值的影响及源项与速度场之间的同步性。通过对方腔顶盖驱动流的数值模拟验证了算法及程序的可靠性和有效性,特别当网格加密到128×128以后,SIMPLEXT算法仍然收敛的突出优越性是SIMPLE等算法无法比拟的。

Determination of Isoflavone from Soybean Lines Cultivated in Jilin Province and Correlation Analysis between Isoflavone Content and Soybean Quality

[Objective]The aim of this study was to set up a high performance liquid chromatography for rapid determination of isoflavones from soybean and analyze the correlation between isofalvone content and protein or fat content. [Method]The isoflavones were firstly extracted by 80% methanol and then hydrolyzed at 100 ℃. The chromatographic separation adopted a reversed-phase C18 analytical column with binary high-pressure gradient elution,while its analysis time was 25 min and column temperature was 40 ℃. The diode array detector was used for monitoring with wavelength of 260 nm. The correlation between isofalvone content and protein or fat content was analyzed by data processing system Origin 6.0. [Result]The high performance liquid chromatograph for determination of isoflavones from soybean was verified to be accurate and reliable by methodology. The isoflavones of 85 soybean lines cultivated in Jilin Province were determined,and the results primarily showed the characters and ranges of isoflavones from soybean lines cultivated in Jilin Province,while the isoflavone content of soybeans ranged from 2.29 to 4.89 mg/g,and the average content was 3.36 mg/g. The isoflavone content of 5 soybean lines exceeded 4 mg/g,while there was a remarkably negative correlation between isoflavone content and protein content,and there was no significant positive correlation between isoflavone content and fat content. [Conclusion]The isoflavone content of soybean lines cultivated in Jilin Province is higher,so it is feasible for breeding the soybean lines with high isoflavone content and fat contetnt.

Krylov子空间法在SIMPLER算法中的求解性能分析

本文开发了Krylov子空间法中的Bi-CGSTAB、GMRES(m)、CGS、TFQMR及QMR方法的计算程序,并将其实施于SIMPLER算法作为其内迭代方法,针对CFD/NHT领域的问题,研究了它们的求解特性;发现: Bi-CGSTAB方法有着高效的收敛速度和良好的稳定性;N-S方程求解中不同方程不同m值的协调选取是GMRES(m)方法在CFD/NHT领域推广应用的关键;CGS和QMR方法易于中断;TFQMR方法收敛速度慢于其他方法,但能适用于更广泛问题的求解。

基于SIMPLER算法的多重网格方法研究

以二维方腔顶盖驱动流为模型,将多重网格方法和SIMPLER算法进行耦合,对不同雷诺数下多重网格加速SIMPLER算法和SIMPLER算法的计算效率进行了对比,数值计算表明:多重网格加速SIMPLER算法不仅能够解决SIMPLER算法不能准确模拟较高雷诺数流场的问题,而且其计算效率远远高于SIMPLER算法。本文也对松弛因子的选取、多重网格实现形式以及网格层数对多重网格加速SIMPLER算法的影响进行了研究,从而为多重网格加速SIMPLER算法的实施提供了计算技术。

一种改进的SIMPLER算法

利用改进的SIMPLER算法即环绕主节点的四个小控制体与推广的QUICK差分格式相结合 ,在非均匀同位网格上求解二维非定常流动与传热的控制方程 .以封闭方腔内的层流自然对流换热问题为例进行了数值模拟 ,计算结果与已有文献一致 ,且得出的平均努赛尔数的计算公式较以前的计算公式精度要高 。

Simultaneous Determination of Four Pesticide Residues in Fruit Juice by HPLC

[Objective] This study was conducted to develop a system for simultaneous determination of imidacloprid, diflubenzuron, thiabendazole and carbendazim in fruit juice by HPLC. [Method] Using acetonitrile as the extraction solvent, the pesticides in fruit juice were purified through a NH2 solid phase extraction （SPE） cartridge, then detected by HPLC. [Result] There was a good linear relationship between the peak area and the concentrations of imidacloprid, diflubenzuron, thiabendazole and carbendazim in a range of 0.05-5.0 μg/ml, and the linear correlation coefficient varied in a range of 0.999 0-0.999 8; the limit of detection for imidacloprid, diflubenzuron, thiabendazole and carbendazim was 0.003, 0.005, 0.003 and 0.007 mg/kg, respectively. The recovery rate of imidacloprid, diflubenzuron, thiabendazole and carbendazim standards added at three levels （0.1, 0.5 and 1.0 mg/kg） ranged from 82% to 107%, with RSD less than 4.5%. [Conclusion] The sensitivity, accuracy and precision of this method were able to meet the requirements for pesticide residue analysis.