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.

Investigation of sex determination in starry flounder(Platichthys stellatus)reveals sex chromosome evolution in Pleuronectiformes and identifies a sex-specific marker

The identification of sex chromosomes is fundamental for exploring the mechanism and evolution of sex determination.Platichthys stellatus,a species exhibiting clear sexual dimorphism and homomorphic chromosome pairs,has received limited research concerning its sex determination mechanisms.Clarifying the sex chromosome of P.stellatus will enhance our understanding of sex chromosome evolution in Pleuronectiformes.This study employed whole-genome resequencing to investigate the sex chromosome and sex determination system in P.stellatus.Notably,Chr23 was identified as the sex chromosome in P.stellatus,with the sex-determining region(SDR)occupying 48.1%of the chromosome and featuring an XX/XY system.Sex chromosome turnover was observed within Pleuronectiformes,with P.stellatus,Verasper variegatus,and Hippoglossus hippoglossus sharing a common ancestral karyotype.No inversions were detected within the SDR of P.stellatus,although chromosomal rearrangements between sex chromosomes and autosomes were identified.Additionally,a sex-specific marker for P.stellatus was ascertained,enabling genetic sex identification,with significant implications for improving breeding programs and aquaculture practices.

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.

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.

Isolation and Biological Determination of Bacillus thuringiensis with High Toxicity in Soil of Changbai Mountain Area

[Objective] This study was conducted to isolate and screen new Bacillus thuringiensis （Bt） strains against Lepidoptera insecticides. [Method] Bt strains were isolated from soil of Changbai Mountain area by temperature screening method, and highly-toxic Bt stains were then selected by biological determination and toxicity de- termination. [Result] From 150 soil samples, 18 Bt isolates were isolated, with an average isolation rate of 12.0%. Specifically, the isolation rate from mountain field was 8.5 %, and the isolation rate from farmland was 16.2%. The results of activity determination showed that there were17, 5 and 4 strains showing lethality rate over 90% against Plutel/a xylosrel/a, Spodoptera litura and Spodptera exigua, respectively, and among them, strain YNI-1 exhibited high activity against all the 3 kinds of in- sects. The results of toxicity determination showed that strain YNl-lhad the best fast-acting property against S.litura and S. exigua; strains with high toxicity against S. exigua were YN6-2〉YN1-1〉YN4-2〉YN2-6 sequentially; and toxicity of strains against S. /itura was in order of YN4-4〉YN1-1 〉YN6-1 〉YN4-1 〉YN2-1. [Conclusion] According to activity determination and toxicity determination, strain YN1-1 was screened as the target strain with wide spectrum, fast-acting property and high toxi- city.

Optimal urban EV charging station site selection and capacity determination considering comprehensive benefits of vehicle-station-grid

This paper presents an optimization model for the location and capacity of electric vehicle(EV)charging stations.The model takes the multiple factors of the“vehicle-station-grid”system into account.Then,ArcScene is used to couple the road and power grid models and ensure that the coupling system is strictly under the goal of minimizing the total social cost,which includes the operator cost,user charging cost,and power grid loss.An immune particle swarm optimization algorithm(IPSOA)is proposed in this paper to obtain the optimal coupling strategy.The simulation results show that the algorithm has good convergence and performs well in solving multi-modal problems.It also balances the interests of users,operators,and the power grid.Compared with other schemes,the grid loss cost is reduced by 11.1%and 17.8%,and the total social cost decreases by 9.96%and 3.22%.

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.

On simulation of precise orbit determination of HY-2 with centimeter precision based on satellite-borne GPS technique

The HY-2 satellite carrying a satellite-borne GPS receiver is the first Chinese radar altimeter satellite, whose radial orbit determination precision must reach the centimeter level. Now HY-2 is in the test phase so that the observations are not openly released. In order to study the precise orbit determination precision and procedure for HY-2 based on the satellite- borne GPS technique, the satellite-borne GPS data are simulated in this paper. The HY-2 satellite-borne GPS antenna can receive at least seven GPS satellites each epoch, which can validate the GPS receiver and antenna design. What＇s more, the precise orbit determination processing flow is given and precise orbit determination experiments are conducted using the HY-2-borne GPS data with both the reduced-dynamic method and the kinematic geometry method. With the 1 and 3 mm phase data random errors, the radial orbit determination precision can achieve the centimeter level using these two methods and the kinematic orbit accuracy is slightly lower than that of the reduced-dynamic orbit. The earth gravity field model is an important factor which seriously affects the precise orbit determination of altimeter satellites. The reduced-dynamic orbit determination experiments are made with different earth gravity field models, such as EIGEN2, EGM96, TEG4, and GEMT3. Using a large number of high precision satellite-bome GPS data, the HY-2 precise orbit determination can reach the centimeter level with commonly used earth gravity field models up to above 50 degrees and orders.

Construction of universal quantitative models for the determination of cefoperazone sodium/sulbactam sodium for injection from different manufacturers using near-infrared reflectance spectroscopy

To develop near-infrared （NIR） reflectance spectroscopic methods for the quantitative analysis of cefoperazone sodium/ sulbactam sodium from different manufacturers for injection powder medicaments. Various powders of cefoperazone sodium/ sulbactam sodium were directly analyzed by non-destructive NIR reflectance spectroscopy using the spectrometer EQUINOX55. Two quantitative methods via integrating sphere （IS） and fiberoptic probe （FOP） models were explored from 6 batches of commercial samples and 42 batches of laboratory samples at a content ranging from 30% to 70% for cefoperazone and 60% to 20% for sulbactam. The root mean square errors of cross validation （RMSECV） and the root mean square errors of prediction （RMSEP） of IS were 1.79% and 2.85%, respectively, for cefoperazone sodium, and were 1.86% and 3.08%, respectively, for sulbactam sodium; and those of FOP were 2.93% and 2.92%, respectively, for cefoperazone sodium, and were 2.23% and 3.01%, respectively, for sulbactam sodium. Based on the ICH guidelines and Ref. 12, the quantitative models were then evaluated in terms of specificity, linearity, accuracy, precision, robustness and model transferability. The non-destructive quantitative NIR methods used in this study are applicable for rapid analysis of injectable powdered drugs from different manufacturers.

Research into Uncertainty in Measurement of Seawater Chemical Oxygen Demand by Potassium Iodide-Alkaline Potassium Permanganate Determination Method

Using the glucose and L-glutamic-acid to prepare the standard substance according to the ratio of 1：1, and the artificial seawater and the standard substance to prepare a series of standard solutions, the distribution pattern of uncertainty in measurement of seawater COD is obtained based on the measured results of the series of standard solutions by the potassium iodide-alkaline potassium permanganate determination method. The distribution pattern is as follows： Uncertainty in measurement is big and not constant at the high end, but small and constant at the low end.

Genetic Determination and Exogenous Influence in Sex Differentiation in Crustacean

The mechanisms of sex determination and the influence of exogenous factors on sex differentiation in crustacean were reviewed in the paper.Most of crustecea have not obviously sex chromosome.Androgenic gland was reported as the most important sex differentiation factors,implanting or cuting AG can change the sexal characterization of larval in crustacean.Although sex differentiation of crustacean is determined by gene,it is affected by exogenous factors such as parasite,photoperiod,temperature or hormone.Most cultured species have different body weight and length between male and female,this can be used in aquaculture to produce all male or female crusteceans to improve the production.

Improved mean-shift-based pitch determination

The underlying principle of pitch determination based on the mean shift algorithm is studied, and the cause of pitch error propagation in the original pseudo code is analyzed. The problem of error propagation is solved by choosing an appropriate initial pitch candidate F00. The theoretical choice guideline in a pitch epoch is obtained as ensuring the true pitch F0 satisfying F00/2 〈 F0 〈 3F00/2. The validity of the choice guideline is verified by the F00 experiment. Meanwhile, the algorithm is extended to the pitch determination in the noisy case and compared with the method of subharmonic-to-harmonic ratio （SHR）. The experimental results show that the improved algorithm bears comparison with SHR and it runs much faster than SHR.

ENGINEERING REALIZATION OF MULTIPLE ANTENNA GPS IN ATTITUDE DETERMINATION INTEGRATED SYSTEM

A multiple antenna GPS system integrated with MEMS-based INS is proposed by data fusion. The system is applied to attitude determination due to its high accuracy, the high output rate, low latency, quick initialization, and good robustness and redundancy. The mathematical method for realizing the system is given. The system can provide attitude and other navigation information even without GPS measurement for a period of time. Experimental results show that, under the condition of 200 Hz, the attitude, the position, the velocity, the acceleration, and the angular rate can achieve 0. 08°/s, 1.5 m, 0. 1 m/s, 0. 12 m/s^2 and 0. 1°/s.

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.

Effects of Different Pretreatment Methods on Determination of Microelements in Feed

[ Objective] To study the effects of different pretreatment methods on determination of microelement in feed and thus find the best pre treatment method for each microetement, t Method] The samples （concentrated feeding stuff and fodder） were pretreated through throe methods, that is, dry incineration method, HNOs HCIO, wetdecomposition method and microwave digestion method. Then the content of seven kinds of mi croelement （AI, Ca, Cu, Fe, Mn, Se and Zn） was determined by inductively coupled plasma atomic emission spectrometer （ICPAES）. I Result] These three methods were all suitable for the determination of Cu, Mn and Zn in concentrated feeding stuff and the determination of Cu and Ca in fodder. The content of Cu and Ca was higher in fodder detected by HNO3 HCIO, wetdecomposition method. The microwave digestion method was suitable for the determination of AI and Ca in concentrated feeding stuff and the determination of AI, Fe, Mn and Zn in fodder. The dry incinera tion method was fit for the determination of Fe in concentrated feeding stuff. [ Condusionl The content of different microelements should be deter mined after the feed is treated with different Ioretreatment methods.