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This study was to evaluate the application of automatic measurement based on convolutional neural network (CNN) technology in intracavitary ultrasound cine of anterior pelvic. A total of 500 patients who underwent pelvic floor ultrasound examination at Peking University Shenzhen Hospital from July 2021 to February 2022 were retrospectively retrieved by the picture archiving and communication system (PACS) system, and 300 cases were used as a training set. The training set was labeled by three experienced ultrasound physicians to train CNN models and develop an automatic measurement software. The remaining 200 cases were used as a test set. Automatic measurement software identified relevant anatomical structures frame by frame and determined the two frames with the greatest difference, calculated the bladder neck descent (BND), urethral rotation angle (URA), and retrovesical angle (RA). Meanwhile, two experienced ultrasound physicians evaluated the resting frame and the maximum Valsalva frame on the cines by manual visual evaluation, labeled the anatomical structures in the corresponding frame, such as the inferoposterior margin of pubic symphysis, the mid‐axis of pubic symphysis, bladder contour, and urethra in the front, and calculated BND, URA, and RA. Considering that the residual urine volume (RUV) in the bladder may affect the results, enrolled patients were grouped according to the RUV (10–50 mL, 50–100 mL, and >100 mL). The consistency of the results by automatic measurement and manual visual evaluation was evaluated using the intraclass correlation coefficient (ICC) and the Bland–Altman graph. Of the 200 cases in the test set, 120 cases were successfully identified by the CNN automatic software with a 60% recognition rate. In the case of successful identification, the ICC of manual visual evaluation measurement and automatic measurement was 0.936 (BND), 0.911 (URA), 0.756 (RA in rest), and 0.877 (RA at maximum Valsalva), respectively. In addition, the RUV had a negligible effect on the consistency. The Bland–Altman plot shows the proportion of samples outside the limit was below 5%. CNN‐based automatic measurement software exhibited high reliability in anterior pelvic measurement, which results in a significantly enhanced measurement efficiency.

Doxorubicin is a common chemotherapeutic agent in clinic, but myocardial toxicity limits its use. Fibroblast growth factor (FGF) 10, a multifunctional paracrine growth factor, plays diverse roles in embryonic and postnatal heart development as well as in cardiac regeneration and repair. In this study we investigated the role of FGF10 as a potential modulator of doxorubicin-induced cardiac cytotoxicity and the underlying molecular mechanisms. Fgf10+/−mice and an inducible dominant negative FGFR2b transgenic mouse model (Rosa26rtTA; tet(O)sFgfr2b) were used to determine the effect of Fgf10hypomorph or blocking of endogenous FGFR2b ligands activity on doxorubicin-induced myocardial injury. Acute myocardial injury was induced by a single injection of doxorubicin (25 mg/kg, i.p.). Then cardiac function was evaluated using echocardiography, and DNA damage, oxidative stress and apoptosis in cardiac tissue were assessed. We showed that doxorubicin treatment markedly decreased the expression of FGFR2b ligands including FGF10 in cardiac tissue of wild type mice, whereas Fgf10+/−mice exhibited a greater degree of oxidative stress, DNA damage and apoptosis as compared with the Fgf10+/+control. Pre-treatment with recombinant FGF10 protein significantly attenuated doxorubicin-induced oxidative stress, DNA damage and apoptosis both in doxorubicin-treated mice and in doxorubicin-treated HL-1 cells and NRCMs. We demonstrated that FGF10 protected against doxorubicin-induced myocardial toxicity via activation of FGFR2/Pleckstrin homology-like domain family A member 1 (PHLDA1)/Akt axis. Overall, our results unveil a potent protective effect of FGF10 against doxorubicin-induced myocardial injury and identify FGFR2b/PHLDA1/Akt axis as a potential therapeutic target for patients receiving doxorubicin treatment.

OBJECTIVE--Glycogen synthase kinase (GSK)-3β plays an important role in cardiomyopathies. Cardiac-specific metallothionein-overexpressing transgenic (MT-TG) mice were highly resistant to diabetes-induced cardiomyopathy. Therefore, we investigated whether metallothionein cardiac protection against diabetes is mediated by inactivation of GSK-3β. RESEARCH DESIGN AND METHODS--Diabetes was induced with streptozotocin in both MT-TG and wild-type mice. Changes of energy metabolism-related molecules, lipid accumulation, inflammation, nitrosative damage, and fibrotic remodeling were examined in the hearts of diabetic mice 2 weeks, 2 months, and 5 months after the onset of diabetes with Western blotting, RT-PCR, and immunohistochemical assays. RESULTS--Activation (dephosphorylation) of GSK-3β was evidenced in the hearts of wild-type diabetic mice but not MT-TG diabetic mice. Correspondingly, cardiac glycogen synthase phosphorylation, hexokinase II, PPARα and PGC-1α expression, which mediate glucose and lipid metabolisms, were significantly changed along with cardiac lipid accumulation, inflammation (TNF-α plasminogen activator inhibitor 1 [PAI-1], and intracellular adhesion molecule 1 [ICAM-1]), nitrosative damage (3-nitrotyrosin accumulation), and fibrosis in the wild-type diabetic mice. The above pathological changes were completely prevented either by cardiac metallothionein in the MT-TG diabetic mice or by inhibition of GSK-3β activity in the wild-type diabetic mice with a GSK-3β-specific inhibitor. CONCLUSIONS--These results suggest that activation of GSK-3β plays a critical role in diabetes-related changes in cardiac energy metabolism, inflammation, nitrosative damage, and remodeling. Metallothionein inactivation of GSK-3β plays a critical role in preventing diabetic cardiomyopathy., Metallothionein, a potent antioxidant, protects against diabetic cardiomyopathy (1-5). However, the mechanisms by which metallothionein protects the heart from diabetes are largely unknown (6). The diabetic heart is characterized by [...]

Peripheral nerve injury (PNI), one of the most common concerns following trauma, can result in a significant loss of sensory or motor function. Restoration of the injured nerves requires a complex cellular and molecular response to rebuild the functional axons so that they can accurately connect with their original targets. However, there is no optimized therapy for complete recovery after PNI. Supplementation with exogenous growth factors (GFs) is an emerging and versatile therapeutic strategy for promoting nerve regeneration and functional recovery. GFs activate the downstream targets of various signaling cascades through binding with their corresponding receptors to exert their multiple effects on neurorestoration and tissue regeneration. However, the simple administration of GFs is insufficient for reconstructing PNI due to their short half‑life and rapid deactivation in body fluids. To overcome these shortcomings, several nerve conduits derived from biological tissue or synthetic materials have been developed. Their good biocompatibility and biofunctionality made them a suitable vehicle for the delivery of multiple GFs to support peripheral nerve regeneration. After repairing nerve defects, the controlled release of GFs from the conduit structures is able to continuously improve axonal regeneration and functional outcome. Thus, therapies with growth factor (GF) delivery systems have received increasing attention in recent years. Here, we mainly review the therapeutic capacity of GFs and their incorporation into nerve guides for repairing PNI. In addition, the possible receptors and signaling mechanisms of the GF family exerting their biological effects are also emphasized.

Recent studies showed that rapamycin improved diabetic complications. Here, we investigated the metabolic effects of rapamycin in type 2 diabetes model (T2DM) mice. Mice were treated with a daily intraperitoneal injection of rapamycin at 2 mg/kg or vehicle only for 3 weeks and were maintained on a high‐fat diet. The treated diabetic mice exhibited decreased body weight, blood glucose levels, and fat mass. FGF21 expression was suppressed in C57B/L6 mice, but adiponectin expression increased both in FGF21 KO and C57B/L6 mice. These results suggest that rapamycin may alleviate FGF21 resistance in mice on a high‐fat diet. The reduction of adipose tissue mass of the diabetic mice may be due to the increased adiponectin.

Overestimation of nitrogen (N) uptake requirement is one of the driving forces of the overuse of N fertilization and the low efficiency of N use in China. In this study, we collected data from 1 844 site-years of rice (Oryza sativaL.) under various rotation cropping systems across the Yangtze River Valley. Selected treatments included without (N0 treatment) and with N application (N treatment) which were recommended by local technicians, with a wide grain range of 1.5–11.9 t ha−1. Across the 1 844 site-years, over 96% of the sites showed yield increase (relative yield>105%) with N fertilization, and the increase rates decreased from 78.9 to 16.2% within the lowest range <4.0 to the highest >6.5 t ha−1. To produce one ton of grain, the rice absorbed approximately 17.8 kg N in the N0 treatment and 20.4 kg N in the N treatment. The value of partial factor productivity by N (PFPN) reached a range of 35.2–51.4 kg grain kg−1with N application under the current recommended N rate. Averaged recovery rate of N (REN) was above 36.0% in yields below 6.0 t ha−1and lower than 31.7% in those above 6.0 t ha−1. Soil properties only affected yield increments within low rice yield levels (<5.5 t ha−1). There is a poor relationship between N application rates and indigenous nitrogen supply (INS). From these observations and considering the local INS, we concluded there was a great potential for improvement in regional grain yield and N efficiency.

Direct-sowing establishment method has great significance in improving winter oilseed rape (Brassica napusL.) production and guaranteeing edible oil security in China. However, nutrient responses on direct sown winter oilseed rape (DOR) performance and population development dynamic are still not well understood. Therefore, five on-farm experiments were conducted in the reaches of the Yangtze River (RYR) to determine the effects of nitrogen (N), phosphorus (P), and potassium (K) deficiencies on population density, dry matter production, nutrient uptake, seed yield, and yield components of DOR plants. Four fertilization treatments included the balanced NPK application treatment (NPK, 180 kg N, 39.3 kg P, 100 kg K, and 1.8 kg borax ha−1) and three nutrient deficiency treatments based on the NPK treatment, i.e., –N, –P, and –K. The results indicated that DOR population density declined gradually throughout the growing season, especially at over-wintering and pod-development stages. Nutrient deficiency decreased nutrient concentration in DOR plants, limited dry matter production and nutrient uptake, and thereby exacerbated density reduction during plants growth. The poor individual growth and reduced population density together decreased seed yield in the nutrient deficiency treatment. Averaged across all the experiments, seed yield reduced 61% by N deficiency, 38.3% by P deficiency, and 14.4% by K deficiency. The negative effects of nutrient deficiency on DOR performances followed the order of –N>–P>–K, and the effects were various among different nutrient deficiencies. Although N deficiency improved DOR emergence, but it seriously limited dry matter production and nutrient uptake, which in turn led to substantial plants death and therefore resulted in a very low harvested density. The P deficiency significantly reduced initial density, limited plants growth, and exacerbated density reduction. The K deficiency mainly decreased individual growth and yield, but did not affect density dynamic. Our results highlighted the importance of balanced NPK application in DOR production, suggesting that management strategy of these nutrients should be comprehensively considered with an aim to build an appropriate population structure with balanced plant density and individual growth.

Based upon the synopsis of software requirement development, this paper describes the practices of user requirements exploitation, product requirements exploitation, requirements analysis and validation, and then puts forward engineering process relation and requirement development practice. Meanwhile, further works are brought forward. This will benefit the software requirement development of information system.

In this study, a regional power planning optimization model (RPPOM) is developed considering the environmental cost and the restriction of resource and environment, based on interval linear programming and mixed integer linear programming. Model is applied to a case study on the power planning in Henan province, and scenario analysis is conducted. Interval solutions associated with scenario of pollution control have been obtained. They can be used for generating decision alternatives and helping decision makers identify desired power policies for power planning to meet the growth in electricity demand considering the constraints of resources and environment with a minimized system cost. Scenario analysis of environmental pollution control at different levels can also be tackled.

Introduction:Though many agents have therapeutic potentials for brain diseases, few have been used in clinical environments because of the brain barriers. As an effective interventional technique, ultrasound (US) could be a potentially feasible approach to disrupt the blood-brain barrier (BBB) and deliver therapeutic agents into the brain.Areas covered:This article reviews up-to-date ultrasound-mediated strategies in opening the brain barriers for drug brain delivery. The mechanisms and problems of these approaches are discussed, as well as the challenges and potentials associated with the ultrasound-mediated strategies that are currently available or under development.Expert opinion:Despite recent successes in opening the blood brain barrier (BBB) via microbubble-enhanced focused ultrasound, the exact mechanisms of how the barrier is disrupted, remains unknown. A complete understanding of the mechanisms involved in the ultrasound-mediated disruption of the BBB and improving the efficiency of drug delivery to targeted brain regions can greatly facilitate the successful development and translation of the technology.

Attitude measurement of the drill bit is the key for horizontal directional drilling, which determines the final positioning accuracy. As for disadvantages of existing algorithms, a method is proposed to get the azimuth, the inclination, and the tool face angle based on gyros. In order to improve attitude measurement accuracy, a quaternion-based attitude complementary filter algorithm is adopted. The accelerometer and magnetometer are used to measure the components of the earth’s gravity field and magnetic field to compensate for gyro drift errors over time, while the gyro ensures the stability of the drill with dynamic acceleration and enhances the robustness of the system. Detailed analysis and simulation results are presented. Results show that the quaternion-based attitude complementary filter algorithm using multiple MARG (Magnetic, Angular Rate, Gravity) sensors can effectively reduce the gyro drift errors and make the attitude measurement error less than +/-0.3 degree.

To clear the agricultural non-point source effects on wetland water environment and the purification efficiency of wetland on non-point pollution. Use the fuzzy comprehensive evaluation method to analyze the water quality conditions of three different urban wetland of Harbin in north shore of Songhua river which affected by human Agriculture activities. Selected Wanbao wetland goose island and sun island water quality monitoring, monitoring time was in October 2004, May 2005, August 2005, and April 2008, a total of four times. The results shown that Wanbao wetland meets water quality planning V water, Goose Island and the sun island meets quality planning IV water. According to fuzzy coefficient can compare the three places wetland water pollution by heavy degree to light for Wanbao wetland > Sun island wetland > Goose island wetland. From upstream to downstream water purification by wetlands, water quality gradually improved.

For the sake of understanding the deterioration behavior of concrete in actual railway tunnel structures subjected to aggressive sulfate medium in practice, detailed field investigations and tested analysis on sprayed concrete linings of approximately 40-year-old railway tunnels in environments containing sulfate ion were carried out, respectively. The results show that the deterioration of concretes in the investigated area is serious, which involves complicated physicochemical process between the sulfate salt and concrete. Among them, the secondary sulfate minerals such as gypsum formation under very high concentration sulfate ion condition by accumulating and evaporation process dominate, followed by the crystallization of sulfate salt and formation of thaumasite.

The amino acid at the 119th position of human basic fibroblast growth factor (hbFGF), lysine (K119), is a critical component for its mitogenic activity. However, little is known about the effects of the characteristics of this residue including charge on the mitogenic activity of hbFGF. Herein, this basic residue was replaced with neutral glutamine residue and acidic glutamic acid residue to construct mutants hbFGFK119Qand hbFGFK119E, respectively. The mutants were produced by BL21(DE3)/pET3c expression system and purified to homogeneity by ionic exchange and heparin affinity chromatography from the supernatant of bacteria lysate. The mitogenic activity analysis showed that neutralization of charge at the 119th residue diminished the mitogenic activity of hbFGF, whereas change of positive charge to negative charge at this residue had no significant effect on its mitogenic activity. Further MAP kinase activation assay revealed that the influence of different charge at the 119th position on the mitogenic activity of hbFGF was related to the signal molecular activation in MAPK pathway. It was deduced that the charge, either positive or negative, at the 119th position of hbFGF is crucial for its full mitogenic activity.

Four naturally rare 5,6,7-trimethoxy-2,3-cis-dihydroflavonols (3–6) and two 5,6,7-trimethoxy-2,3-trans-dihydroflavonols (7–8) were designed and synthesized. Their antioxidative properties were evaluated by way of examining their scavenging capacities towards DPPH and O2− free radicals, as well as by measuring their inhibitory ability against LPO. Both the 2,3-trans and the 2,3-cis conformers exhibited certain quenching abilities to DPPH and O2− radicals, while most of the synthetic dihydroflavonols demonstrated remarkable inhibition to LPO.

Twelve 23-esterified silybin derivatives with different patterns of substituents such as aromatic and aliphatic groups (1–12) were designed and synthesized. The antioxidative properties of these compounds were evaluated. The modified silybin analogues exhibited improved inhibitory effects against rat liver homogenate lipid peroxidation compared to silybin, with exception of the trimethoxylated ester (5) and the aliphatic one (9). Compounds 3, 5, 7, 8 and 11 displayed their protective properties on DNA cleavage in a dose-dependent manner.

Proliferating cells express cyclins, cell cycle regulatory proteins that regulate the activity of cyclin-dependent kinases (CDKs). The actions of CDKs are regulated by specific inhibitors, the CDK inhibitors (CDKIs), which are comprised of the Cip/Kip and INK4 families. Expression of the Cip/Kip CDKI 1B (Cdkn1b, encoding protein CDKN1B, also called p27kip1) in developing Leydig cells (LCs) has been reported, but the function of CDKN1B in LCs is unclear. The goal of the present study was to determine the effects of CDKN1B on LC proliferation and steroidogenesis by examining these parameters in Cdkn1bknockout (Cdkn1b−/−) mice. LC proliferation was measured by bromodeoxyuridine incorporation. Testicular testosterone levels, mRNA levels, and enzyme activities of steroidogenic enzymes were compared in Cdkn1b−/−and Cdkn1b+/+mice. The labeling index of LCs in Cdkn1b−/−mice was 1.5% ± 0.2%, almost 7-fold higher than 0.2% ± 0.08% (P< 0.001) in the Cdkn1b+/+control mice. LC number per testis in Cdkn1b−/−mice was 2-fold that seen in the Cdkn1b+/+control mice. However, testicular testosterone levels, mRNA levels of steroidogenic acute regulatory protein (Star), cholesterol side-chain cleavage enzyme (Cyp11a1), and 3beta-hydroxtsteroid dehydrogenase 6 (Hsd3b6), and their respective proteins, were significantly lower in Cdkn1b−/−mice. We conclude that deficiency of CDKN1B increased LC proliferation, but decreased steroidogenesis. Thus, CDKN1B is an important regulator of LC development and function.

A pH-responsive polymer Eudragit S-100 has been found to assist in correct folding of FGF-2 (fibroblast growth factor-2) denatured with 8mol/L urea and 10mmol/L dithiothreitol at pH 7.2. The refolding of FGF-2 was performed by directly diluting denatured FGF-2 into a refolding buffer containing Eudragit S-100. The ability of Eudragit S-100 to enhance protein refolding level was investigated using MTT method, fluorescence emission spectroscopy and reverse phase HPLC. On the other hand, the result shows the ability of Eudragit S-100 to enhance the refolding level of protein is due to the interaction between Eudragit S-100 and positively charged FGF-2.

Three new compounds, including one chloro-furoeremophilanoid (1), one eremophiladiolide (2), a rare dimer of nor-furoeremophilanoid, ligulatrovine A (3), and a known furoeremophilanolide (4), were isolated from Ligularia atroviolacea. The structures of compounds 1–4were elucidated by spectroscopic methods including 1D and 2D NMR experiments as well as X-ray diffraction study.

Three new diarylheptanoids, i.e., sodium(5S,2E)-1,7-bis(4-hydroxyphenyl)-1-hydroxy-2-hepten-5-sulfonate (1), sodium(5R,2E)-1,7-bis(4-hydroxyphenyl)-1-hydroxy-2-hepten-5-sulfonate (2) and 3,5-diacetoxy-1-(3-methoxy-4,5-dihydroxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane (3) were isolated from the rhizomes of Zingiber officinale. The structures of the new compounds were elucidated on the basis of spectroscopic methods. The antioxidant activities of 3 were assayed by in vitro models involving DPPH free radicals and superoxide anion radicals.

Both zinc and copper are essential minerals that are required for various cellular functions. Although these metals are essential, they can be toxic at excess amounts, especially in certain genetic disorders. Zinc and copper homeostasis results from a coordinated regulation by different proteins involved in uptake, excretion and intracellular storage/trafficking of these metals. Apart from zinc transporters (ZnT) families and Cu-ATPase, metallothionein is an important storage protein for zinc and copper. Metallothioneins are intracellular polypeptides with a remarkable ability to bind metallic ions. These proteins bind both essential metals indispensable for the organism and also toxic metals (e.g. cadmium or lead). Metallothioneins play a critical role to maintain zinc and copper homeostasis. In this review, we summarize the toxicity of zinc and copper and the potential treatment for zinc or copper toxicity by zinc- or copper-specific chelators as well as strategy to upregulate metallothionein.

Zinc (Zn) is an essential mineral that is required for various cellular functions. Its abnormal metabolism is related to certain disorders such as diabetic complications. Oxidative stress has been considered as the major causative factor for diabetic cardiomyopathy. Zn has a critical antioxidant action in protecting the heart from various oxidative stresses. Zn deficiency was found to be a risk factor for cardiac oxidative damage and supplementation with Zn provides a significant prevention of oxidative damage to the heart. Diabetes causes a significant systemic oxidative stress and also often is accompanied by Zn deficiency that increases the susceptibility of the heart to oxidative damage. Therefore, there is a strong rationale to consider the strategy of Zn supplementation to prevent or delay diabetic cardiomyopathy. This short article collects the preliminary evidence, based on our own studies and those by others, for a preventive effect of Zn supplementation on diabetes-induced injury to the heart in animals and under in vitro conditions. Possible mechanisms by which Zn supplementation prevents diabetic heart disease are discussed. They include an antioxidant action of Zn, insulin function and metallothionein induction. In the final section, the future of Zn supplementation for diabetic patients is also briefly discussed. Although Zn supplementation has not been clinically used to prevent diabetic complications, because several issues need to be addressed, the fact that Zn supplementation is being used clinically for other disorders encourages us to explore its direct clinical application for the prevention of diabetic cardiomyopathy.

A new cyclic diarylheptanoid, 1,5-epoxy-3-hydroxy-1-(3-methoxy-4,5-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptane (1), as well as a new monoterpene, 10-O-β-d-glucopyranosyl-hydroxy cineole (2) were isolated from the rhizomes of Zingiber officinale. The structures of compounds 1 and 2 were established based on their spectral data. In addition, the antioxidant activities of these compounds were also measured.

Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne virus that carries a high fatality rate of 12%–50%. In-depth understanding of the SFTSV-induced pathogenesis mechanism is critical for developing effective anti-SFTS therapeutics. Here, we report transcriptomic analysis of blood samples from SFTS patients. We observe a strong correlation between inflammatory responses and disease progression and fatal outcome. Quantitative proteomic analysis of SFTSV infection confirms the induction of inflammation and further reveals virus-induced mitochondrial dysfunction. Mechanistically, SFTSV infection triggers BCL2 antagonist/killer 1 (BAK) upregulation and BAK/BCL2-associated X (BAX) activation, leading to mitochondrial DNA (mtDNA) oxidization and subsequent cytosolic release. The cytosolic mtDNA binds and triggers NLRP3 inflammasome activation. Notably, the BAK expression level correlates with SFTS disease progression and fatal outcome. These findings provide insights into the clinical features and molecular underpinnings of severe SFTS, which may aid in patient care and therapeutic design, and may also be conserved during infection by other highly pathogenic viruses.

Arginine deficiency is involved in thrombocytopenia and immunosuppression in severe fever with thrombocytopenia syndrome.

Normal numbers of adult Leydig cells per testis are maintained primarily from the normal proliferation of its progenitors. Postnatal development of Leydig cells in rodents can be divided into four distinct stages of differentiation: initially, fibroblast-like stem Leydig cells (SLCs) proliferate by postnatal days (PND) 7 to 14, and then they commit to fibroblast-like progenitor Leydig cells (PLCs) by PND14-21; subsequently, as immature Leydig cells (ILCs) by PND21-35, they acquire steroidogenic organelle structure and enzyme activities but metabolize most of the testosterone they produce; finally, as adult Leydig cells (ALCs) by PND90 they actively produce testosterone. Targeted gene deletion of insulin-like growth factor-I (IGFIKO) results in diminished numbers of adult Leydig cells and lower circulating testosterone levels in adult males. The aims of the present study were to determine dynamic proliferating and differentiating profiles of ALC population during postnatal period in IGFIKO mice. Testicular cells in mice were labeled by injection of BrDU and testes were collected by PND7, 14, 21, 28, 35, 56 and 90. Leydig cells were immunohistochemically stained using 3β-hydroxysteroid dehydrogenase (3β-HSD) antibody and analyzed. Putative SLCs become proliferative at PND7 and 14 in wild-typed testis with labeling index (LI) of 10.8 ± 4.6 (Mean ± SEM, n=10), LI of SLC greatly decreased through PND 21-56, and LI peaked for PLCs at PND 21 and LI for ILCs peaked at PND35. LI of SLCs did not change in IGFIKO mice (7.4 ± 3.3) compared to wild-type mice, while PLCs and ILCs did not proliferate through PND14 to PND90 in IGFIKO mouse testis. The Leydig cell number and cell size were significantly reduced in IGFIKO adult testis, e.g. at PND90, 980 ± 155 cells/mm2and 132.6 ± 6.4 μm2compared to 1876 ± 116 cells/mm2and 280.9 ± 10.6 μm2in wild-type testis, respectively. The differentiation of SLCs into PLCs was not affected since the numbers of PLCs formed at PND14 was the same with 161 ± 12 cells/mm2for mutant and 196 ± 36 cells/mm2for wild-type mice. However, the differentiation of PLCs into ILCs and ALCs were greatly delayed. At PND90, total Leydig cell numbers, percentage of PLCs increased from 1.06 ± 0.14 in wild-type mice to 20.4 ± 3.54 in IGFIKO mice. The present study demonstrated that the lacking of proliferation of PLCs and ILCs in IGFIKO mice accounted the reduced number of adult population of Leydig cells. Although the commitment of SLCs into PLCs was not affected in IGFIKO mice, the differentiation of PLCs into ALCs was significantly affected. The research was supported in part by NIH grant RO1 HD050570-01A2.