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.

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.

Maleness-on-the-Y(MoY) orthologue is a key regulator of male sex determination in Zeugodacus cucurbitae(Diptera:Tephritidae)

The initiation of sex differentiation in insects is regulated by primary sex determination signals.In the Medfly Ceratitis capitata and other tephritids,Maleness-on-the-Y(MoY) is the master gene for male sex determination.However,the primary signal in Zeugodacus cucurbitae(Coquillett),a very destructive tephritid pest across the world,remains ambiguous.In this study,we have isolated and characterized the Medfly MoY homolog in Z.cucurbitae,ZcMoY.ZcMOY protein shows high sequence conservation to its homologs in Bactrocera species.ZcMoY transcription begins and peaks at very early embryonic stages and then becomes undetectable except the testes and heads of day 1 male adults.Silencing ZcMoY in early embryos by RNAi causes abnormal external genitalia and interior reproductive organs,giving rise to intersexes and feminization of XY individuals.The expression pattern and knockdown phenotypes of ZcMoY indicate that ZcMoY plays a key role in regulating sex determination of Z.cucurbitae males.Our findings will help the understanding of sex determination in Z.cucurbitae and facilitate the development of genetic sexing strains in its biological control.

X-ray在鱼体组织及微量元素检测中的应用

鱼类硬质组织物,特别是骨骼支持鱼体和保护其体内器官的组织,对其进行特征检测分析是研究鱼类游泳运动、鱼类解剖、鱼体建模等的数据基础。随着X-ray技术的发展和国产设备的广泛应用,其仪器设备成本明显降低,使得X-ray在渔业研究与自动化生产中的应用成为可能。首先介绍了X-ray技术的基本原理与其在鱼体组织检测中的应用,X-ray技术在鱼体组织及微量元素检测中的应用主要分为鱼类组织器官的无损检测和鱼体微量元素检测两部分,其中分别介绍了包括照相法、数字成像法、衍射技术和吸收光谱法等X-ray技术;然后综述其在鱼体组织器官建模、鱼骨检测、鱼类化石研究、鱼耳石分析和鱼体微量元素检测方面的应用,总结了Xray在渔业领域应用中存在的问题;最后对X-ray的渔业应用方向进行展望。

The Soft X-ray Imager(SXI)on the SMILE Mission

The Soft X-ray Imager(SXI)is part of the scientific payload of the Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)mission.SMILE is a joint science mission between the European Space Agency(ESA)and the Chinese Academy of Sciences(CAS)and is due for launch in 2025.SXI is a compact X-ray telescope with a wide field-of-view(FOV)capable of encompassing large portions of Earth’s magnetosphere from the vantage point of the SMILE orbit.SXI is sensitive to the soft X-rays produced by the Solar Wind Charge eXchange(SWCX)process produced when heavy ions of solar wind origin interact with neutral particles in Earth’s exosphere.SWCX provides a mechanism for boundary detection within the magnetosphere,such as the position of Earth’s magnetopause,because the solar wind heavy ions have a very low density in regions of closed magnetic field lines.The sensitivity of the SXI is such that it can potentially track movements of the magnetopause on timescales of a few minutes and the orbit of SMILE will enable such movements to be tracked for segments lasting many hours.SXI is led by the University of Leicester in the United Kingdom(UK)with collaborating organisations on hardware,software and science support within the UK,Europe,China and the United States.

Global hybrid simulations of soft X-ray emissions in the Earth’s magnetosheath

Earth’s magnetopause is a thin boundary separating the shocked solar wind plasma from the magnetospheric plasmas,and it is also the boundary of the solar wind energy transport to the magnetosphere.Soft X-ray imaging allows investigation of the large-scale magnetopause by providing a two-dimensional(2-D)global view from a satellite.By performing 3-D global hybrid-particle-in-cell(hybrid-PIC)simulations,we obtain soft X-ray images of Earth’s magnetopause under different solar wind conditions,such as different plasma densities and directions of the southward interplanetary magnetic field.In all cases,magnetic reconnection occurs at low latitude magnetopause.The soft X-ray images observed by a hypothetical satellite are shown,with all of the following identified:the boundary of the magnetopause,the cusps,and the magnetosheath.Local X-ray emissivity in the magnetosheath is characterized by large amplitude fluctuations(up to 160%);however,the maximum line-of-sight-integrated X-ray intensity matches the tangent directions of the magnetopause well,indicating that these fluctuations have limited impact on identifying the magnetopause boundary in the X-ray images.Moreover,the magnetopause boundary can be identified using multiple viewing geometries.We also find that solar wind conditions have little effect on the magnetopause identification.The Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)mission will provide X-ray images of the magnetopause for the first time,and our global hybrid-PIC simulation results can help better understand the 2-D X-ray images of the magnetopause from a 3-D perspective,with particle kinetic effects considered.

Comparison between Double Crystals X-ray Diffraction and Micro-Raman Measurement on Composition Determination of High Ge Content Si_(1-x)Ge_(x) Layer Epitaxied on Si Substrate

It is important to acquire the composition of Si1-xGex layer, especially that with high Ge content, epitaxied on Si substrate. Two nondestructive examination methods, double crystals X-ray diffraction （DCXRD） and micro-Raman measurement, were introduced comparatively to determine x value in Si1-xGex layer, which show that while the two methods are consistent with each other when x is low, the results obtained from double crystals X-ray diffraction are not credible due to the large strain relaxation occurring in Si1-xGex layers when Ge content is higher than about 20%. Micro-Raman measurement is more appropriate for determining high Ge content than DCXRD.

Finding the magnetopause location using soft X-ray observations and a statistical inverse method

Variability in the location and shape of the dayside magnetopause is attributed to magnetic reconnection,a fundamental process that enables the transfer of mass,energy,and momentum from the solar wind into the magnetosphere.The spatial and temporal properties of the magnetopause,under varying solar and magnetospheric conditions,remain largely unknown because empirical studies using in-situ observations are challenging to interpret.Global wide field-of-view(FOV)imaging is the only means to simultaneously observe the spatial distribution of the plasma properties over the vast dayside magnetospheric region and,subsequently,quantify the energy transport from the interplanetary medium into the terrestrial magnetosphere.Two upcoming missions,ESA/CAS SMILE and NASA’s LEXI will provide wide-field imagery of the dayside magnetosheath in soft X-rays,an emission generated by charge exchange interactions between high charge-state heavy ions of solar wind origin and exospheric neutral atoms.High-cadence two-dimensional observations of the magnetosheath will allow the estimation of dynamic properties of its inner boundary,the magnetopause,and enable studies of its response to changes in the solar wind dynamic pressure and interplanetary magnetic field orientation.This work introduces a statistically-based estimation approach based on inverse theory to estimate the spatial distribution of magnetosheath soft X-ray emissivities and,with this,identify the location of the magnetopause over the Sun−Earth line.To do so,we simulate the magnetosheath structure using the MHD-based OpenGGCM model and generate synthetic soft X-ray images using LEXI’s orbit and attitude information.Our results show that 3-D estimations using the described statistically-based technique are robust against Poisson-distributed shot noise inherent to soft X-ray images.Also,our proposed methodology shows that the accuracy of both three-dimensional(3-D)estimation and the magnetopause standoff distance calculation highly depends on the observational point.

Two methods for separating the magnetospheric solar wind charge exchange soft X-ray emission from the diffuse X-ray background

Solar wind charge exchange(SWCX)is the process of solar wind high-valence ions exchanging charges with neutral components and generating soft X-rays.Recently,detecting the SWCX emission from the magnetosphere is proposed as a new technique to study the magnetosphere using panoramic soft X-ray imaging.To better prepare for the data analysis of upcoming magnetospheric soft X-ray imaging missions,this paper compares the magnetospheric SWCX emission obtained by two methods in an XMM-Newton observation,during which the solar wind changed dramatically.The two methods differ in the data used to fit the diffuse X-ray background(DXB)parameters in spectral analysis.The method adding data from the ROSAT All-Sky Survey(RASS)is called the RASS method.The method using the quiet observation data is called the Quiet method,where quiet observations usually refer to observations made by the same satellite with the same target but under weaker solar wind conditions.Results show that the spectral compositions of magnetospheric SWCX emission obtained by the two methods are very similar,and the changes in intensity over time are highly consistent,although the intensity obtained by the RASS method is about 2.68±0.56 keV cm^(-2)s^(-1)sr^(-1)higher than that obtained by the Quiet method.Since the DXB intensity obtained by the RASS method is about 2.84±0.74 keV cm^(-2)s^(-1)sr^(-1)lower than that obtained by the Quiet method,and the linear correlation coefficient between the difference of SWCX and DXB obtained by the two methods in diffe rent energy band is close to-1,the diffe rences in magnetospheric SWCX can be fully attributed to the diffe rences in the fitted DXB.The difference between the two methods is most significant when the energy is less than 0.7 keV,which is also the main energy band of SWCX emission.In addition,the difference between the two methods is not related to the SWCX intensity and,to some extent,to solar wind conditions,because SWCX intensity typically va ries with the solar wind.In summary,both methods are robust and reliable,and should be considered based on the best available options.

SMILE soft X-ray Imager flight model CCD370 pre-flight device characterisation

Throughout the SMILE mission the satellite will be bombarded by radiation which gradually damages the focal plane devices and degrades their performance.In order to understand the changes of the CCD370s within the soft X-ray Imager,an initial characterisation of the devices has been carried out to give a baseline performance level.Three CCDs have been characterised,the two flight devices and the flight spa re.This has been carried out at the Open University in a bespo ke cleanroom measure ment facility.The results show that there is a cluster of bright pixels in the flight spa re which increases in size with tempe rature.However at the nominal ope rating tempe rature(-120℃) it is within the procure ment specifications.Overall,the devices meet the specifications when ope rating at -120℃ in 6 × 6 binned frame transfer science mode.The se rial charge transfer inefficiency degrades with temperature in full frame mode.However any charge losses are recovered when binning/frame transfer is implemented.

Estimating the subsolar magnetopause position from soft X-ray images using a low-pass image filter

The Lunar Environment heliospheric X-ray Imager(LEXI)and Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)missions will image the Earth’s dayside magneto pause and cusps in soft X-rays after their respective launches in the near future,to specify glo bal magnetic reconnection modes for varying solar wind conditions.To suppo rt the success of these scientific missions,it is critical to develop techniques that extract the magnetopause locations from the observed soft X-ray images.In this research,we introduce a new geometric equation that calculates the subsolar magnetopause position(RS)from a satellite position,the look direction of the instrument,and the angle at which the X-ray emission is maximized.Two assumptions are used in this method:(1)The look direction where soft X-ray emissions are maximized lies tangent to the magnetopause,and(2)the magnetopause surface near the subsolar point is almost spherical and thus RSis nea rly equal to the radius of the magneto pause curvature.We create synthetic soft X-ray images by using the Open Geospace General Circulation Model(OpenGGCM)global magnetohydrodynamic model,the galactic background,the instrument point spread function,and Poisson noise.We then apply the fast Fourier transform and Gaussian low-pass filte rs to the synthetic images to re move noise and obtain accurate look angles for the soft X-ray pea ks.From the filte red images,we calculate RS and its accuracy for different LEXI locations,look directions,and solar wind densities by using the OpenGGCM subsolar magnetopause location as ground truth.Our method estimates RS with an accuracy of<0.3 RE when the solar wind density exceeds>10 cm-3.The accuracy improves for greater solar wind densities and during southward interplanetary magnetic fields.The method ca ptures the magnetopause motion during southwa rd interplaneta ry magnetic field turnings.Consequently,the technique will enable quantitative analysis of the magnetopause motion and help reveal the dayside reconnection modes for dynamic solar wind conditions.This technique will suppo rt the LEXI and SMILE missions in achieving their scientific o bjectives.