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. .

Risk Factors for Mortality in Critically Ill Patients with Coagulation Abnormalities:A Retrospective Cohort Study

Objective Coagulation abnormalities are common and prognostically significant in intensive care units(ICUs)and are associated with increased mortality.This study aimed to explore the association between the levels of coagulation markers and the risk of mortality among ICU patients with coagulation abnormalities.Methods This retrospective study investigated patients with coagulation abnormalities in the ICU between January 2021 and December 2022.The initial point for detecting hemostatic biomarkers due to clinical assessment of coagulation abnormalities was designated day 0.Patients were followed up for 28 days,and multivariate logistic regression analysis was utilized to identify risk factors for mortality.Results Of the 451 patients analyzed,115 died,and 336 were alive at the end of the 28-day period.Multivariate analysis revealed that elevated thrombin-antithrombin complex(TAT),tissue plasminogen activator inhibitor complex(tPAIC),prolonged prothrombin time,and thrombocytopenia were independent risk factors for mortality.For nonovert disseminated intravascular coagulation(DIC)patients,older age and thrombocytopenia were associated with increased risks of mortality,whereas elevated levels of plasminα2-plasmin inhibitor complex(PIC)were found to be independent predictors of survival.In patients with overt DIC,elevated levels of tPAIC were independently associated with increased risks of mortality.Nevertheless,thrombocytopenia was independently associated with increased risks of mortality in patients with pre-DIC.Conclusion Coagulation markers such as the TAT,tPAIC,PIC,and platelet count were significantly associated with mortality,underscoring the importance of maintaining a balance between coagulation and fibrinolysis.These findings highlight the potential for targeted therapeutic interventions based on specific coagulation markers to improve patient outcomes.

Comparison between sepsis-induced coagulopathy and sepsis-associated coagulopathy criteria in identifying sepsis-associated disseminated intravascular coagulation

BACKGROUND:Disseminated intravascular coagulation(DIC)is associated with increased mortality in sepsis patients.In this study,we aimed to assess the clinical ability of sepsis-induced coagulopathy(SIC)and sepsis-associated coagulopathy(SAC)criteria in identifying overt-DIC and preDIC status in sepsis patients.METHODS:Data from 419 sepsis patients were retrospectively collected from July 2018 to December 2022.The performances of the SIC and SAC were assessed to identify overt-DIC on days 1,3,7,or 14.The SIC status or SIC score on day 1,the SAC status or SAC score on day 1,and the sum of the SIC or SAC scores on days 1 and 3 were compared in terms of their ability to identify pre-DIC.The SIC or SAC status on day 1 was evaluated as a pre-DIC indicator for anticoagulant initiation.RESULTS:On day 1,the incidences of coagulopathy according to overt-DIC,SIC and SAC criteria were 11.7%,22.0%and 31.5%,respectively.The specificity of SIC for identifying overt-DIC was significantly higher than that of the SAC criteria from day 1 to day 14(P<0.05).On day 1,the SIC score with a cut-off value>3 had a significantly higher sensitivity(72.00%)and area under the curve(AUC)(0.69)in identifying pre-DIC than did the SIC or SAC status(sensitivity:SIC status 44.00%,SAC status 52.00%;AUC:SIC status 0.62,SAC status 0.61).The sum of the SIC scores on days 1 and 3 had a higher AUC value for identifying the pre-DIC state than that of SAC(0.79 vs.0.69,P<0.001).Favorable effects of anticoagulant therapy were observed in SIC(adjusted hazard ratio[HR]=0.216,95%confidence interval[95%CI]:0.060–0.783,P=0.018)and SAC(adjusted HR=0.146,95%CI:0.041–0.513,P=0.003).CONCLUSION:The SIC and SAC seem to be valuable for predicting overt-DIC.The sum of SIC scores on days 1 and 3 has the potential to help identify pre-DIC.

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.

Effects of Coagulation and Ozonation Pretreatments on Biochemical Treatment of Fluid Catalytic Cracking Wastewater

Fluid catalytic cracking (FCC) salty wastewaters, containing quaternary ammonium compounds (QACs), are very difficult to treat by biochemical process. Anoxic/oxic (A/O) biochemical system, based on nitrification and denitrification reactions, was used to assess their possible biodegradation. Because of the negative effects of high salt concentration (3%), heavy metals and toxic organic matter on microorganisms’ activities, some techniques consisting of dilution, coagulation and flocculation, and ozonation pretreatments, were gradually tested to evaluate chemical oxygen demand (COD), ammonia-nitrogen (ammonia-N) and total nitrogen (TN) removal rates. In this process of FCC wastewater, starting with university-domesticated sludge, the ammonia-N and TN removal rates were worst. However, when using domesticated SBR’s sludge and operating with five-fold daily diluted influent (thus reducing salt concentration), the ammonia-N removal reached about 57% while the TN removal rate was less than 37% meaning an amelioration of the nitrification process. However, by reducing the dilution factors, these results were inflected after some days of operation, with ammonia-N removal decreasing and TN barely removed meaning a poor nitrification. Even by reducing heavy metals concentration with coagulation/flocculation process, the results never changed. Thereafter, by using ozonation pre-treatment to degrade the detected organic matter of di-tert-butylphenol and certain isoparaffins, COD, ammonia-N and TN removal rates reached 92%, 62% and 61%, respectively. These results showed that the activities of the microorganisms were increased, thus indicating a net denitrification and nitrification reactions improvement.

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.

Hybrid argon plasma coagulation for the treatment of Barrett’s esophagus:A prospective,multicenter study

BACKGROUND The incidence of Barrett’s esophagus(BE)in China is lower compared to the Western populations.Hence,studies conducted in the Chinese population has been limited.The current treatment options available for BE treatment includes argon plasma coagulation(APC),radiofrequency ablation and cryoablation,all with varying degrees of success.AIM To determine the efficacy and safety of HybridAPC in the treatment of BE.METHODS The study cohort consisted of patients with BE who underwent HybridAPC ablation treatment.These procedures were performed by seven endoscopists from different tertiary hospitals.The duration of the procedure,curative rate,complications and recurrent rate by 1-year follow-up were recorded.RESULTS Eighty individuals were enrolled for treatment from July 2017 to June 2020,comprising of 39 males and 41 females with a median age of 54 years(range,30 to 83 years).The technical success rate of HybridAPC was 100%and the overall curative rate was 98.15%.No severe complications occurred during the operation.BE cases were classified as short-segment BE and long-segment BE.Patients with short-segment BE were all considered cured without complications.Thirty-six patients completed the one-year follow-up without recurrence.Twenty-four percent had mild dysplasia which were all resolved with one post-procedural treatment.The mean duration of the procedure was 10.94±6.52 min.CONCLUSION Treatment of BE with HybridAPC was found to be a simple and quick procedure that is safe and effective during the short-term follow-up,especially in cases of short-segment BE.This technique could be considered as a feasible alternative ablation therapy for BE.

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.

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.

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.

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.

Virus Removal by Iron Coagulation Processes

Waterborne viruses account for 30% to 40% of infectious diarrhea, and some viruses could persevere for some months in nature and move up to 100 m in groundwater. Using filtration setups, coagulation could lessen virus charges as an efficient pre-treatment for reducing viruses. This work discusses the present-day studies on virus mitigation using coagulation in its three versions i.e., chemical coagulation (CC), enhanced coagulation, and electrocoagulation (EC), and debates the new results of virus demobilization. The complexity of viruses as bioparticles and the process of virus demobilization should be adopted, even if the contribution of permeability in virus sorption and aggregation needs to be clarified. The information about virion permeability has been evaluated by interpreting empirical electrophoretic mobility (EM). No practical measures of virion permeability exist, a clear link between permeability and virion composition and morphology has not been advanced, and the direct influence of inner virion structures on surface charge or sorption has yet to be conclusively demonstrated. CC setups utilizing zero-valent or ferrous iron could be killed by iron oxidation, possibly using EC and electrooxidation (EO) methods. The oxidants evolution in the iron oxidation method has depicted promising findings in demobilizing bacteriophage MS2, even if follow-up investigations employing an elution method are needed to secure that bacteriophage elimination is related to demobilization rather than sorption. As a perspective, we could be apt to anticipate virus conduct and determine new bacteriophage surrogates following subtle aspects such as protein structures or genome size and conformation. The present discussion’s advantages would extend far beyond an application in CC—from filtration setups to demobilization by nanoparticles to modeling virus fate and persistence in nature.

Coagulation abnormalities and their relationship with bleeding manifestations in patients with dengue-A single center observational study

Objective:To evaluate coagulation abnormalities and their relationship with bleeding manifestations among patients with dengue.Methods:This observational study was conducted on 292 adult dengue patients who were admitted to a tertiary care hospital of Western India from July 2021 to June 2022.Coagulation tests including prothrombin time(PT),international normalized ratio(INR),activated partial thromboplastin time(aPTT),fibrinogen,and D-dimer were performed.Patients were monitored for bleeding manifestations.Results:Coagulation abnormalities were reported in 42.8%of the patients.Overall,prolonged aPTT was the most common coagulation abnormality(40.8%),followed by low fibrinogen(38.7%),raised D-dimer(31.2%),raised INR(26.0%)and prolonged PT(19.2%).Bleeding manifestations were present in 19.9%patients.PT,INR,aPTT and D-dimer levels were significantly higher(P<0.01)and fibrinogen level was significantly lower(P<0.001)in patients with bleeding compared to patients without bleeding.Patients with bleeding had a significantly higher rate of all coagulation abnormalities than patients without bleeding(P<0.01).Conclusions:Patients with bleeding showed a significantly higher frequency of coagulation abnormalities compared to patients without bleeding.Patients with dengue should be assessed for coagulation abnormalities.

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.

Soxllb regulates the migration and fate determination of Müller glia-derived progenitors during retina regeneration in zebrafish

The transcription factor Sox11 plays important roles in retinal neurogenesis during vertebrate eye development.However,its function in retina regeneration remains elusive.Here we report that Sox11 b,a zebrafish Sox11 homolog,regulates the migration and fate determination of Müller glia-derived progenitors(MGPCs)in an adult zebrafish model of mechanical retinal injury.Following a stab injury,the expression of Sox11 b was induced in proliferating MGPCs in the retina.Sox11 b knockdown did not affect MGPC formation at 4 days post-injury,although the nuclear morphology and subsequent radial migration of MGPCs were alte red.At 7 days post-injury,Sox11 b knockdown res ulted in an increased proportion of MGPCs in the inner retina and a decreased propo rtion of MGPCs in the outer nuclear layer,compared with controls.Furthermore,Sox11 b knockdown led to reduced photoreceptor regeneration,while it increased the numbe rs of newborn amacrines and retinal ganglion cells.Finally,quantitative polymerase chain reaction analysis revealed that Sox11 b regulated the expression of Notch signaling components in the retina,and Notch inhibition partially recapitulated the Sox11 b knockdown phenotype,indicating that Notch signaling functions downstream of Sox11 b.Our findings imply that Sox11 b plays key roles in MGPC migration and fate determination during retina regeneration in zebrafish,which may have critical im plications for future explorations of retinal repair in mammals.