Intracerebroventricular injection of RFRP-3 delays puberty onset and stimulates growth hormone secretion in female rats.

BACKGROUND: Puberty onset is a complex, organized biological process with multilevel regulation, and its physiopathological mechanisms are yet to be elucidated. RFRP-3, the mammalian ortholog to gonadotropin-inhibitory hormone, is implicated in inhibiting the synthesis and release of gonadotropin in mammals. However, it is unclear whether RFRP-3 participates in regulating pubertal development. METHODS: This study investigated the functional significance and regulatory mechanism of hypothalamic RFRP-3 neuropeptide in the onset of puberty in young female rats. On postnatal day 22, we implanted cannulas into the lateral ventricles of female rat pups. From postnatal day 28 to postnatal day 36, the intracerebroventricular injection of RFRP-3, or vehicle, was conducted twice a day. To investigate whether puberty onset was affected, we examined the body weight, age of vaginal opening, serum hormone levels, uterus and ovary development, and hypothalamic Kiss-1 mRNA expression. RESULTS: Intracerebroventricular injection of RFRP-3 significantly decreased the serum concentrations of luteinizing hormone and estradiol, delayed uterine maturation, and postponed the time of vaginal opening. This study suggests that RFRP-3 can delay the onset of puberty in young female rats; the expression of Kiss-1 mRNA is potently inhibited in the RFRP-3 group. Moreover, our data show that RFRP-3 elevates serum growth hormone levels. CONCLUSIONS: These data suggest that intracerebroventricular injection of RFRP-3 significantly delays the onset of puberty in female rats. Additionally, RFRP-3 may be associated with prepubertal rise in the secretion of growth hormone.

Ultrasonic Non-Destructive Detection Method for Residual Stress in Rotary Forging Aluminum Alloy Plates.

Aluminum alloy plates are widely used to manufacture large-scale integral structure parts in the field of aerospace. During the forming and processing of aluminum alloy plates, different degrees of residual stress are inevitably produced. Fast and accurate detection of residual stress is very essential to ensuring the quality of these plates. In this work, the longitudinal critically refracted (LCR) wave detection method based on a one-transmitter and double-receiver (OTDR) transducer and the finite element simulation were employed to obtain the residual stress. Aluminum alloy plates with different deformation amounts were fabricated by rotary forging to obtain different residual stress states. Results reveal that the plate formed by rotary forging is in a stress state of central tension and edge compression. As the deformation increases from 20% to 60%, the peak residual tensile stress increases from 156 MPa to 262 MPa, and there is no significant difference in the peak compressive stress. When the deformation reaches 60%, the difference in the residual stresses at different depths is less than 13%, which indicates that the plastic deformation zone basically penetrates the entire longitudinal cross-section of the plate. The maximum deviation between measurement and FE is 61 MPa, which means the experimental data are in good agreement with the FE results.

Precise Shrink Fitting Design of the High Strength Gear Mold for the Precision Forging of Noncircular Spur Bevel Gears.

Shrink fitting of forging mold (SFFM) is an effective method for improving mold strength, extending the mold's service life and reducing the manufacturing cost of forging mold. However, due to the asymmetric geometry and complex stress distribution, the precise design of SFFM for the precision forging of noncircular bevel gears is very difficult. In this paper, a new precise design method of SFFM for the precision forging of noncircular bevel gears is proposed, which mainly includes the following five parts. First, a new design method for the mold parting surface-the curved surface parting method-is proposed to design the forging mold of noncircular spur bevel gears. Then, new dimension design methods for the gear mold and shrink rings based on the uniform shrinkage force are proposed. Third, a new design method for the inhomogeneous interference value between shrink rings and the gear mold is developed to provide a precise, uniform shrinkage force. After that, a strength correction method for the shrink-fitted gear mold is proposed to ensure the gear mold and shrink rings have sufficient strength both in the assembly process of the shrink-fitted gear mold and precision in the forging process of noncircular spur bevel gears. Ultimately, finite element simulations and verification experiments are performed to verify the proposed precise design method of SFFM for the precision forging of noncircular bevel gears. The precise design method of SFFM proposed in this paper is not only applicable to the precise design of the high-strength gear mold for noncircular bevel gears, but can also provide a valid reference for the precise design of the high-strength mold for other complicated asymmetric parts.

Grain Refinement Mechanism of 5A06 Aluminum Alloy Sheets during Cold Rotary Forging.

This paper studies the grain refinement mechanisms of 5A06 aluminum alloy sheets in cold rotary forging (CRF). The results show that the grains are clearly refined from 25.1 µm to 11.8 µm during the CRF process. The grain refinement mechanism can be divided into two modes: (1) The grains with a small Schmid factor (SF) are activated by multi-slip systems, and dense dislocations are segregated along the boundaries of interior regions with different slip systems, which results in a rapidly increasing strain localization along these boundaries. Since the strain localization restrains the coordinate slip deformation between different interior regions, the grains are directly separated into several finer grains. (2) The grains with a large SF are primarily activated by a single slip system, and the dislocation migrates smoothly along most microband boundaries. Then, a more severe lattice rotation causes a transformation to a hard orientation and multi-slip system activation, which contributes to an increase in the rapid misorientation across microband boundaries and thus promotes significant SF grain refinement.

Erratum to "Effect of Nephropathy Prescription I on the Expression of Angptl3 and Podocyte-Associated Protein in Mice with Adriamycin-Induced Nephropathy".

[This corrects the article DOI: 10.1155/2022/9921679.].

Numerical Simulation of Intelligent Fuzzy Closed-Loop Control Method for Radial-Axial Ring Rolling Process of Super-Large Rings.

During the radial-axial ring rolling (RARR) process of super-large rings, abnormal deformation states such as instability and out of circularity often lead to rolling termination and quality fluctuation of ring products. In this work, an intelligent fuzzy closed-loop control method for RARR process of super-large rings is proposed, i.e., the ring's offset adaptive fuzzy control (ROAFC) based on the regulation of the axial roll's rotational speed and the ring's circularity fuzzy control (RCFC) based on the regulation of the mandrel's feed speed. In addition, a recursive average filtering algorithm is added to smooth the axial roll's rotational speed and the mandrel's feed speed according to the actual situation. Using the ABAQUS/Explicit software and its subroutine VUAMP, the intelligent fuzzy controller of the ring's offset and circularity in the RARR process is designed, and the finite element (FE) model for RARR process of a Φ10 m super-large ring with an integrated intelligent fuzzy control algorithm is established. The variation laws of the ring's offset and circularity error in the RARR process are studied with regard to different control methods such as conventional planning control (CPC), ROAFC, RCFC, and comprehensive control of ROAFC combined with RCFC (ROAFC + RCFC). The results obtained show that, compared with the CPC, the ring's offset is reduced by 84.6% and the circularity error is decreased by 51.9% in the RARR process utilizing comprehensive control of ROAFC + RCFC. The research results provide methodological guidance for realizing the intelligent forming of super-large rings.

Effect of Nephropathy Prescription I on the Expression of Angptl3 and Podocyte-Associated Protein in Mice with Adriamycin-Induced Nephropathy.

Objective: This study aimed to investigate the effects of Nephropathy Prescription I on the expression of angptl3, nephrin, and podocin, in addition to its protective effects on podocytes in mice with adriamycin-induced nephropathy. Methods: BALB/c mice were randomly divided into the control (C), adriamycin (Model or M), adriamycin + Nephropathy Prescription I (M + Z), adriamycin + prednisone acetate (M + S), and adriamycin + Nephropathy Prescription I + prednisone acetate groups (M + Z + S). All mice except those in the C group in the experimental groups were treated with a single tail vein injection of adriamycin. The urine albumin-creatinine ratio was measured before model establishment and on the 7th day, 14th day, 21st day, and 28th day of doxorubicin injection. All the mice were sacrificed on the 29th day. Blood samples were collected to observe biochemical indicators in the serum. The morphological structure and podocyte ultrastructure in the kidney were observed using light and electron microscopy, respectively. The expression of angptl3, nephrin, and podocin at the mRNA and protein levels was detected by real-time PCR and western blotting, respectively. Results: Following modeling with adriamycin, albuminuria was observed in urine samples in the first week, and the urinary protein/creatinine ratio increased maximally in the fourth week in the M group (P < 0.05). In contrast, the urinary protein/creatinine ratio significantly decreased (P < 0.05) in the third week in the (M + Z) group compared to that in the M group. Similarly, this ratio decreased in the (M + S) and (M + Z + S) groups compared to that in the M group throughout the experiment. Compared with the C group, serum albumin content and the expression of nephrin and podocin decreased (P < 0.05), whereas blood lipid level and the expression of angptl3 increased (P < 0.05) in the M group. Glomerular foot process fusion was observed in this group using electron microscopy. In all the intervention groups, serum albumin content and the expression of nephrin and podocin increased (P < 0.05), whereas blood lipid level and the expression of angptl3 decreased (P < 0.05), with alleviated glomerular foot process injury observed particularly in the (M + Z + S) group. Conclusion: The Nephropathy Prescription I can alleviate albuminuria, increase serum albumin levels, lower blood lipid levels, and reduce the fusion of foot processes of podocytes in mice with adriamycin-induced nephropathy. The protective effects of the Nephropathy Prescription I may function by reducing Angptl3 expression and increasing nephrin and podocin expression.

Precocious Puberty and the Lin28/Let7 Pathway: The Therapeutic Effect of the Nourishing "Yin" and Purging "Fire" Traditional Chinese Medicine Mixture in a Rat Model.

The present study aims to investigate the effects of the nourishing "Yin" and purging "Fire" Traditional Chinese Medicine (TCM) herb mixture on precocious puberty and TCM may act through hypothalamic Lin28/let7 pathway expression in the precocious puberty model rats. Meanwhile, to confirm the relationship between Lin28/let7 pathway and puberty by overexpression Lin28a, in the first part of this study, female rats were randomly allocated into untreated controls, the precocious puberty (PP) model group, the PP control group, and the PP + TCM group. Rats on postnatal day 5 were injected danazol to establish the PP model. From days 15 to 35, the rats in the TCM group were given the TCM twice daily. Vaginal opening, sex-related hormones, and body and reproductive organ weights were measured, and the expressions of hypothalamic Lin28a and Lin28b mRNA and let7a and let7b miRNA were detected. In addition, in the second part, the effects of overexpression of Lin28a on the vaginal opening time were evaluated. In the two parts of the study, we found that, at the onset of puberty, a decrease in ovary weight, an increase in the serum levels of luteinizing hormone and progesterone, and increased expression levels of hypothalamic Lin28b mRNA were observed in the PP + TCM group compared to the PP model group. The vaginal opening time was significantly delayed upon overexpression of Lin28a. Above all, the mechanism by which the TCM treats precocious puberty is thus likely to be associated with inhibition of the hypothalamic Lin28/let7 signaling pathway and our findings provide in-depth insight into the relationship between the overexpression of Lin28a gene in the hypothalamus and the onset of puberty.

Effectiveness of ZiYin Xiehuo granules and Zishen Qinggan granules on partial precocious puberty in girls: a multicenter, randomized, single-blind, controlled trial.

OBJECTIVE: To evaluate the effect of ZiYin Xiehuo granules (ZYXH) and Zishen Qinggan granules (ZSQG) on partial precocious puberty (PPP). METHODS: This was a multicenter, randomized, single-blind, positive-controlled trial. A total of 143 patients were assigned to either the ZYXH group or the ZSQG group using a random number table. The ZYXH group received ZYXH three times daily for 6 months and the ZSQG group received ZSQG three times daily for 6 months. Mammary nucleus diameter; the results of uterus, ovarian, and maximum follicle measures; and Chinese medicine symptom pattern scores were compared at baseline and after 3 months and 6 months of treatment. RESULTS: After 3 months' treatment, there were no significant differences between the two groups in mammary nucleus index changes (left 3.4 ± 3.1 vs 3.5 ± 3.1, P = 0.790; right 3.0 ± 2.9 vs 3.6 ± 3.0, P = 0.719). The uterine volume in the ZYXH group was smaller than that in the ZSQG group (2.1 ± 1.6 vs 2.6 ± 2.2, P = 0.006). There were no significant between-group differences in ovarian volume and maximum follicular diameter on either side (ovarian volume: left 1.2 ± 0.7 vs 1.3 ± 0.6, P = 0.8; right 1.2 ± 0.7 vs 1.4 ± 1.1, P = 0.984; maximum follicular diameter: left 3.9 ± 1.7 vs 3.5 ± 2.2, P = 0.158; right 3.5 ± 1.7 vs 3.9 ± 2.1, P = 0.314). CONCLUSION: ZYXH granules and ZSQG granules both affected the size of the mammary nucleus in girls with PPP, and improved Chinese medicine symptom patterns. ZYXH granules showed slight advantages over ZSQG granules in terms of the decrease in the size of the uterus, ovaries, and ovarian follicles.

Effect of Nourishing "Yin" Removing "Fire" Chinese Herbal Mixture on Hypothalamic Mammalian Target of Rapamycin Expression during Onset of Puberty in Female Rats.

Aim. The present study aims to investigate the effects of nourishing "Yin" removing "Fire" (NYRF) Chinese herbal mixture on puberty onset and hypothalamic mTOR expression in female rats. Materials and Methods. Forty female 20-day-old Sprague-Dawley rats were randomly divided into Chinese herbal mixture (CHM) and normal saline (NS) groups. Rats in CHM and NS were treated with NYRF mixture and normal saline, respectively, from d22. Rats in each group were sacrificed on d28, d31, and d34. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), and estradiol (E2) levels were analyzed by ELISA. Hypothalamic mTOR mRNA expression levels were determined by RT-PCR and hypothalamic p-mTOR protein levels were assayed by western blot. Results. The vaginal opening time in CHM group was significantly delayed (P < 0.05). On d31, in comparison with NS group, the coefficients of uteri and ovaries, levels of serum LH and E2, and the expression levels of hypothalamic mTOR mRNA and p-mTOR protein were significantly lower in CHM group (P < 0.05). Conclusion. The mechanism by which the nourishing "Yin" removing "Fire" Chinese herbal mixture delays puberty onset may be associated with the inhibition of the hypothalamic mTOR signaling.