The correlation between sperm percentage with a small acrosome and unexplained in vitro fertilization failure.

PURPOSE: Since the unexplained in vitro fertilization failure occurs frequently, it is of great importance and clinical value to identify potential underlying predictors. This study aimed to explore whether the percentage of sperm with a small acrosome was correlated with unexplained in vitro fertilization failure. METHODS: A new acrosomal function evaluation index (the percentage of sperm with a small acrosome) was introduced into the analysis of sperm morphology. The association between the index and acrosome function by acrosin activity detection test and acrosome reaction test was investigated. In addition, the correlation with unexplained in vitro fertilization failure was further explored. Finally, the ROC curve was used to analyze the diagnostic efficacy on the failure of in vitro fertilization and the cutoff value was calculated. RESULTS: As the increasing of the percentage of sperm with a small acrosome, the value of acrosin activity, acrosome reaction rate, and in vitro fertilization rate were reduced, with a statistically significant difference (P < 0.05). The index in the low fertilization rate group was significantly higher than that in the normal fertilization rate group (P < 0.05). Finally, the results of ROC curve found that when the index was 43.5%, the sensitivity and specificity were 74.2% and 95.3%, respectively. CONCLUSION: The percentage of sperm with a small acrosome was positively correlated with unexplained in vitro fertilization failure, which could be potentially used as a prognostic index for the failure of in vitro fertilization. TRIAL REGISTRATION: [Ethics review acceptance No IIT20210339B].

Study on the Consistency Between Automatic Measurement Based on Convolutional Neural Network Technology and Manual Visual Evaluation in Intracavitary Ultrasonic Cine of Anterior Pelvic.

OBJECTIVES: This study was to evaluate the application of automatic measurement based on convolutional neural network (CNN) technology in intracavitary ultrasound cine of anterior pelvic. METHODS: 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. RESULTS: 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%. CONCLUSIONS: CNN-based automatic measurement software exhibited high reliability in anterior pelvic measurement, which results in a significantly enhanced measurement efficiency.

Establishment and Validation of a Transdermal Drug Delivery System for the Anti-Depressant Drug Citalopram Hydrobromide.

To enhance the bioavailability and antihypertensive effect of the anti-depressant drug citalopram hydrobromide (CTH) we developed a sustained-release transdermal delivery system containing CTH. A transdermal diffusion meter was first used to determine the optimal formulation of the CTH transdermal drug delivery system (TDDS). Then, based on the determined formulation, a sustained-release patch was prepared; its physical characteristics, including quality, stickiness, and appearance, were evaluated, and its pharmacokinetics and irritation to the skin were evaluated by applying it to rabbits and rats. The optimal formulation of the CTH TDDS was 49.2% hydroxypropyl methyl cellulose K100M, 32.8% polyvinylpyrrolidone K30, 16% oleic acid-azone, and 2% polyacrylic acid resin II. The system continuously released an effective dose of CTH for 24 h and significantly enhanced its bioavailability, with a higher area under the curve, good stability, and no skin irritation. The developed CTH TDDS possessed a sustained-release effect and good characteristics and pharmacokinetics; therefore, it has the potential for clinical application as an antidepressant.

[Methods for research on structures and functions of traditional Chinese medicine proteins].

Traditional Chinese medicine proteins(TCMPs) not only have nutritional values and biological activities but also serve as key enzymes in the synthesis of pharmacodynamic components in traditional Chinese medicines. They play a role in the synthesis of pharmacodynamic components by regulating biosynthesis and selective synthesis pathways and controlling drug quality and stability. The recent years have witnessed great progress in the research on the structures and functions of proteins using various methods and technologies. However, the research on the structures and functions of TCMPs lags behind. Therefore, it is urgent to study the structures and functions of TCMPs using modern means to promote the discovery of innovative drugs based on TCMPs and clarify the synthesis pathways of pharmacodynamic components. This study introduces the latest techniques for studying protein structures and functions, including spectroscopy, mass spectrometry, nuclear magnetic resonance, X-ray crystal diffraction, microscopy, and structure prediction. Furthermore, this paper introduces the methods for protein functional studies, including liquid chromatography-mass spectrometry, co-immunoprecipitation, yeast two-hybrid, and pull-down assay. By systematically reviewing these techniques and methods, this paper provides technical references for the structural identification and functional studies of TCMPs, with the aim of promoting the in-depth exploration of the structures and functions of TCMPs.

Iberiotoxin and clofilium regulate hyperactivation, acrosome reaction, and ion homeostasis synergistically during human sperm capacitation.

Potassium channels play essential roles in the regulation of male fertility. However, potassium channels mediating K+ currents in human sperm (IKSper ) remain controversial. Besides SLO3, the SLO1 potassium channel is a potential candidate for human sperm KSper. This study intends to elucidate the function of SLO1 potassium channel during human sperm capacitation. Human sperm were treated with iberiotoxin (IbTX, a SLO1 specific inhibitor) and clofilium (SLO3 inhibitor) separately or simultaneously during in vitro capacitation. A computer-assisted sperm analyzer was used to assess sperm motility. The sperm acrosome reaction (AR) was analyzed using fluorescein isothiocyanate-conjugated Pisum sativum agglutinin staining. Sperm protein tyrosine phosphorylation was studied using western blotting. Intracellular Ca2+ , K+ , Cl- , and pH were analyzed using ion fluorescence probes. Independent inhibition with IbTX or clofilium decreased the sperm hyperactivation, AR, and protein tyrosine phosphorylation, and was accompanied by an increase in [K+ ]i , [Cl- ]i , and pHi , but a decrease in [Ca2+ ]i . Simultaneously inhibition with IbTX and clofilium lower sperm hyperactivation and AR more than independent inhibition. The increase in [K+ ]i , [Cl- ]i , and pHi , and the decrease in [Ca2+ ]i were more pronounced. This study suggested that the SLO1 potassium channel may have synergic roles with SLO3 during human sperm capacitation.

Reversible Single-Crystal-to-Single-Crystal Transformation of a Coordination Polymer through Solar-Switchable Cycloaddition and Cycloreversion Reaction.

Reversible covalent reactions within crystalline complexes are powerful tools for the design and developing of new generation of reusable smart materials. In this work, a unique photoreactive olefin-containing metal-organic coordination polymer [Ag2(2,3-ppe)2(1,3-bdc)]n (1) was prepared by the hydrothermal reaction between AgNO3, 1-(2-pyridyl)-2-(3-pyridyl)ethylene (2,3-ppe), and 1,3-benzenedicarboxylic acid (1,3-H2bdc). When exposed to sunlight, 1 can undergo single-crystal-to-single-crystal (SCSC) transformation to form [Ag2(dpdpcb)(1,3-bdc)]n (1a, dpdpcb = 1,3-di(2-pyridyl)-2,4-di(3-pyridyl)cyclobutane) through a [2 + 2] cycloaddition reaction. 1a can regenerate into 1 via the cycloreversion reaction based on the thermal effect of sunlight. Such a metal-organic complex exhibits interesting fluorescence switching behavior during the unprecedented fully solar-controlled reversible SCSC reaction, which makes it possible to be applied to the fields of optical memory storage and anti-counterfeiting.

Potential metal-related strategies for prevention and treatment of COVID-19.

Abstract: The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed severe threats to human health, public safety, and the global economy. Metal nutrient elements can directly or indirectly take part in human immune responses, and metal-related drugs have served as antiviral drugs and/or enzyme inhibitors for many years, providing potential solutions to the prevention and treatment of COVID-19. Metal-based drugs are currently under a variety of chemical structures and exhibit wide-range bioactivities, demonstrating irreplaceable advantages in pharmacology. This review is an intention to summarize recent progress in the prevention and treatment strategies against COVID-19 from the perspective of metal pharmacology. The current and potential utilization of metal-based drugs is briefly introduced. Specifically, metallohydrogels that have been shown to present superior antiviral activities are stressed in the paper as potential drugs for the treatment of COVID-19.

Hsp90 modulates human sperm capacitation via the Erk1/2 and p38 MAPK signaling pathways.

BACKGROUND: Heat shock protein 90 (Hsp90) is a highly abundant eukaryotic molecular chaperone that plays important roles in client protein maturation, protein folding and degradation, and signal transduction. Previously, we found that both Hsp90 and its co-chaperone cell division cycle protein 37 (Cdc37) were expressed in human sperm. Hsp90 is known to be involved in human sperm capacitation via unknown underlying mechanism(s). As Cdc37 was a kinase-specific co-chaperone of Hsp90, Hsp90 may regulate human sperm capacitation via other kinases. It has been reported that two major mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase 1/2 (Erk1/2) and p38, are expressed in human sperm in the same locations as Hsp90 and Cdc37. Phosphorylated Erk1/2 has been shown to promote sperm hyperactivated motility and acrosome reaction, while phosphorylated p38 inhibits sperm motility. Therefore, in this study we explored whether Hsp90 modulates human sperm capacitation via the Erk1/2 and p38 MAPK signaling pathways. METHODS: Human sperm was treated with the Hsp90-specific inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) during capacitation. Computer-assisted sperm analyzer (CASA) was used to detect sperm motility and hyperactivation. The sperm acrosome reaction was analyzed by using fluorescein isothiocyanate-conjugated Pisum sativum agglutinin (PSA-FITC) staining. The interactions between Hsp90, Cdc37, Erk1/2 and p38 were assessed using co-immunoprecipitation (Co-IP) experiments. Western blotting analysis was used to evaluate the levels of protein expression and phosphorylation. RESULTS: Human sperm hyperactivation and acrosome reaction were inhibited by 17-AAG, suggesting that Hsp90 is involved in human sperm capacitation. In addition, Co-IP experiments revealed that 17-AAG reduced the interaction between Hsp90 and Cdc37, leading to the dissociation of Erk1/2 from the Hsp90-Cdc37 protein complex. Western blotting analysis revealed that levels of Erk1/2 and its phosphorylated form were subsequently decreased. Decreasing of Hsp90-Cdc37 complex also affected the interaction between Hsp90 and p38. Nevertheless, p38 dissociated from the Hsp90 protein complex and was activated by autophosphorylation. CONCLUSIONS: Taken together, our findings indicate that Hsp90 is involved in human sperm hyperactivation and acrosome reaction. In particular, Hsp90 and its co-chaperone Cdc37 form a protein complex with Erk1/2 and p38 to regulate their kinase activity. These results suggest that Hsp90 regulates human sperm capacitation via the Erk1/2 and p38 MAPK signaling pathways.

Crystallographic Visualization of a Guest-Induced Solar-Driven Cycloaddition Reaction Based on a Recyclable Nonporous Coordination Polymer.

Stimuli-responsive solids with adjustable photophysical properties are particularly attractive because they can be used as smart materials in anticounterfeiting, information storage, holographic imaging, and other fields. Herein, we report a unique nonporous coordination polymer, {[Ag(3,3'-dpe)](2,2'-Hbpdc)}n (1; 3,3'-dpe = 1,2-dipyridin-3-ylethene and 2,2'-H2bpdc = 2,2'-biphenyldicarboxylic acid), that can convert to an extremely photoreactive compound, 1·H2O·MeCN (MeCN = acetonitrile), through guest capture. Upon irradiation of sunlight, 1·H2O·MeCN can transform to {[Ag(3,3'-tpcb)0.5](2,2'-Hbpdc)(H2O)(MeCN)}n (2·H2O·MeCN; 3,3'-tpcb = 1,2,3,4-tetrapyridin-3-ylcyclobutane). 2·H2O·MeCN can lose its solvent molecules to form 2 and further return to 1 at high temperature. Accompanied by direct visualization based on multistep single-crystal-to-single-crystal conversions, the recyclable crystalline solid exhibits remarkable fluorescence changes, which makes it a supramolecular switch for application in multiple anticounterfeiting.

Activation of VEGF receptors in response to UVB promotes cell proliferation and melanogenesis of normal human melanocytes.

VEGF receptors (VEGFRs) are high-affinity receptors for VEGF and signaling via VEGFRs extends beyond the classical roles in blood vessel formation. We previously showed VEGFRs were also expressed in epidermal keratinocytes and activation of VEGFR-2 by ultraviolet B (UVB) was involved in the pro-survival mechanism. Here, we show that both VEGF165 and UVB enhanced the expression of VEGFRs (including VEGFR-1, VEGFR-2 and NRP-1) in normal human melanocytes, and increased expression of VEGFRs by UVB was mediated through hypoxia and oxidative stress. Also, VEGF165 and UVB promoted tyrosine phosphorylation of VEGFR-1 and VEGFR-2, and UVB-induced phosphorylation of VEGFR-1 and VEGFR-2 required PKA but not P38 MAPK. In addition, UVB and VEGF165 contributed to the over-expression of melanogenic proteins in melanocytes, which could be reduced by neutralization of VEGFR-1 and/or VEGFR-2. UVB, but not VEGF165 promoted cell proliferation, while neutralization of VEGFR-1 and/or VEGFR-2 abolished this effect. UVB showed stronger than VEGF165 in promoting tyrosinase activity and melanin production, while neutralization of VEGFR-2 was stronger in reducing these effects than that of VEGFR-1. Furthermore, tranexamic acid (TA) decreased tyrosinase activity and melanin production via inhibiting activation of VEGFRs and subsequent expression of melanogenic proteins in melanocytes. Taken together, we demonstrate that VEGFRs are functionally involved in UVB-induced melanogenesis, and TA can inhibit melanogenesis at least in part by targeting VEGFRs in melanocytes.

The Seminiferous Epithelial Cycle of Spermatogenesis: Role of Non-receptor Tyrosine Kinases.

Non-receptor tyrosine kinases (NRTKs) are implicated in various biological processes including cell proliferation, differentiation, survival, and apoptosis, as well as cell adhesion and movement. NRTKs are expressed in all mammals and in different cell types, with extraordinarily high expression in the testis. Their association with the plasma membrane and dynamic subcellular localization are crucial parameters in their activation and function. Many NRTKs are found in endosomal protein trafficking pathways, which suggests a novel mechanism to regulate the timely junction restructuring in the mammalian testis to facilitate spermiation and germ cell transport across the seminiferous epithelium.

Src family kinases (SFKs) and cell polarity in the testis.

Non-receptor Src family kinases (SFKs), most notably c-Src and c-Yes, are recently shown to be expressed by Sertoli and/or germ cells in adult rat testes. Studies have shown that SFKs are involved in modulating the cell cytoskeletal function, and involved in endocytic vesicle-mediated protein endocytosis, transcytosis and/or recycling as well as intracellular protein degradation events. Furthermore, a knockdown to SFKs, in particular c-Yes, has shown to induce defects in spermatid polarity. These findings, coupled with emerging evidence in the field, thus prompt us to critically evaluate them to put forth a developing concept regarding the role of SFKs and cell polarity, which will become a basis to design experiments for future investigations.

Tranexamic Acid Inhibits Angiogenesis and Melanogenesis in Vitro by Targeting VEGF Receptors.

Melasma is a common but complex skin condition concerning cosmetic problems. Tranexamic acid (TA) has been proved to be effective in treatment of melasma with still unclear mechanisms. Here, we show that VEGF165 enhanced the expression of VEGF receptors (VEGFRs, including VEGFR-1, VEGFR-2 and NRP-1) in human umbilical vein endothelial cells (HUVECs), which was attenuated by TA. VEGF165 also promoted tyrosine phosphorylation of VEGFR-1 and VEGFR-2 in HUVECs, which was again abolished by TA. TA further showed similar effects to neutralization of VEGFR-1 and VEGFR-2 in inhibiting cell proliferation, migration, invasion and tube formation of HUVECs induced by VEGF165, suggesting that TA could inhibit angiogenesis by targeting VEGFRs in HUVECs. In addition, VEGF165 enhanced the expression of VEGFRs and promoted tyrosine phosphorylation of VEGFR-1 and VEGFR-2 in normal human melanocytes, which were also attenuated by TA. Furthermore, TA showed similar effects to neutralization of VEGFR-1 and VEGFR-2 in inhibiting tyrosinase activity, melanin production and even melanogenic proteins induced by VEGF165, suggesting that TA could reduce melanogenesis via inhibiting activation of VEGFRs and subsequent expression of melanogenic proteins in melanocytes. Taken together, we demonstrate that TA can inhibit angiogenesis and melanogenesis in vitro at least in part by targeting VEGFRs, which may offer a new understanding of the pathogenesis of melasma as well as the molecular mechanism for TA in treatment of the disease.

Helicobacter pylori infection is associated with elevated galactose-deficient IgA1 in IgA nephropathy.

Background: Mucosal immunity plays an important role in the pathogenesis of IgA nephropathy (IgAN). This study aimed to investigate if infection of Helicobacter pylori (H. pylori), a common bacteria in the gastrointestinal tract, associated with IgAN.Methods: This study included 261 patients with IgAN and 46 healthy controls. Clinical information and plasma samples were collected from patients and healthy controls. H. pylori infection was confirmed by western blot. Plasma IgA1 and galactose-deficient IgA1 (Gd-IgA1) levels were detected by specific enzyme-linked immunosorbent assay.Results: Total H. pylori infection rates showed no statistical differences between IgAN patients and healthy controls, but the infection rates of type I H. pylori in IgAN patients were significantly higher than those in healthy controls (44.4 vs. 28.3%, p = 0.040). Compared with uninfected patients, the systolic blood pressure, 24-h proteinuria, and blood urea nitrogen levels were significantly higher in patients with H. pylori infection (126.0 ± 15.5 vs. 119.6 ± 14.5 mmHg, p = 0.010; 1.8 ± 2.7 vs. 1.2 ± 1.4 g/24h, p = 0.013; 7.9 ± 5.4 vs. 6.7 ± 3.9 µmol/L, p = 0.042), especially in patients with type I infection (126.5 ± 15.4 vs. 119.6 ± 14.5 mmHg, p = 0.002; 1.9 ± 2.9 vs. 1.2 ± 1.4 g/24 h, p = 0.033; 8.1 ± 5.6 vs. 6.7 ± 3.9 µmol/L, p = 0.041). Similarly, patients with IgAN and type I H. pylori infection showed higher plasma Gd-IgA1 levels than uninfected patients (5.5 ± 2.2 vs. 4.5 ± 2.2 µg/mL, p = 0.037).Conclusions: Virulent type I H. pylori infection is more common in patients with IgAN. Patients with IgAN and type I H. pylori infection showed lower renal function and higher underglycosylation of plasma IgA1.

Comparison of interleukin-6, interleukin-10, procalcitonin and C-reactive protein in identifying high-risk febrile illness in pediatric cancer patients: A prospective observational study.

The aim of this study is to systematically compare the performance of C-reactive protein (CRP), procalcitonin (PCT) and serum cytokines in identifying pediatric cancer patients with high-risk infection. A prospective observational study was performed from January 2014 through December 2016. Consecutive pediatric cancer patients who experienced febrile illness during hospitalization were enrolled. The CRP, PCT, interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were determined within 6 h of fever onset. A total of 3118 episodes of febrile illness were included, with 13.1% episodes documented as bloodstream infection (BSI) and 3.5% diagnosed as septic shock. Patients with BSI presented much higher levels of PCT, IL-6, IL-10 and TNF-α than patients with other types of fever and have much higher incidence of septic shock (11.2% vs. 2.3%, P < 0.001). IL-6 and IL-10 showed better performance in identifying patients with gram-negative bacteremia (GNB) and septic shock than CRP and PCT, respectively. The area under the curve (AUCs) of receiver operating characteristic (ROC) curve for septic shock prediction were 0.65, 0.78, 0.89 and 0.87 for CRP, PCT, IL-6 and IL-10, respectively. Furthermore, elevation of IL-6 and IL-10 were strongly associated with the development of GNB and septic shock. Our results indicate that BSI, especially GNB, is a high-risk form of infection which results in high incidence of septic shock. IL-6 and IL-10 performance better than CRP and PCT in identifying patients with high-risk febrile illness.

Emerging role for SRC family kinases in junction dynamics during spermatogenesis.

SRC family kinases (SFKs) are known regulators of multiple cellular events, including cell movement, differentiation, proliferation, survival and apoptosis. SFKs are expressed virtually by all mammalian cells. They are non-receptor protein kinases that phosphorylate a variety of cellular proteins on tyrosine, leading to the activation of protein targets in response to environmental stimuli. Among SFKs, SRC, YES and FYN are the ubiquitously expressed and best studied members. In fact, SRC, the prototypical SFK, was the first tyrosine kinase identified in mammalian cells. Studies have shown that SFKs are regulators of cell junctions, and function in endocytosis and membrane trafficking to regulate junction restructuring events. Herein, we briefly summarize the recent findings in the field regarding the role of SFKs in the testis in regulating spermatogenesis, particularly in Sertoli-Sertoli and Sertoli-germ cell adhesion. While it is almost 50 years since the identification of the oncogene v-Src encoded by Rous sarcoma transforming virus, the understanding of SFK involvement during spermatogenesis in the testis remains far behind that in other epithelia and tissues. The goal of this review is to bridge this gap.

Selenium Deficiency Aggravates Aflatoxin B1-Induced Immunotoxicity in Chick Spleen by Regulating 6 Selenoprotein Genes and Redox/Inflammation/Apoptotic Signaling.

BACKGROUND: Selenium (Se) plays a protective role in aflatoxin B1 (AFB1)-induced splenic immunotoxicity in chicks. OBJECTIVE: This study was designed to reveal the underlying mechanism of Se-mediated protection against AFB1-induced splenic injury in broilers. METHODS: Four groups of 1-d-old Cobb male broilers (n = 5 cages/diet, 6 chicks/cage) were arranged in a 3-wk 2 × 2 factorial design trial whereby they were fed an Se-deficient, corn- and soy-based diet [base diet (BD), 36 µg Se/kg], BD plus 1.0 mg AFB1/kg, BD plus 0.3 mg Se/kg, or BD plus 1.0 mg AFB1/kg and 0.3 mg Se/kg (as 2-hydroxy-4-methylselenobutanoic acid). Serum and spleen were collected at week 3 to assay for cytokines, histology, redox status, selected inflammation- and apoptosis-related genes and proteins, and the selenogenome. RESULTS: Dietary AFB1 induced growth retardation and spleen injury, decreasing (P < 0.05) body weight gain, feed intake, feed conversion efficiency, and serum interleukin-1ß by 17.8-98.1% and increasing (P < 0.05) the spleen index and serum interleukin-6 by 37.6-113%. It also reduced the splenic lymphocyte number, the white pulp region, and histiocyte proliferation in Se-adequate groups. However, Se deficiency aggravated (P < 0.05) these AFB1-induced alterations by 16.2-103%. Moreover, Se deficiency decreased (P < 0.05) splenic glutathione peroxidase (GPX) activity and glutathione-S transferase and glutathione concentrations by 35.6-89.4% in AFB1-exposed groups. Furthermore, Se deficiency upregulated (P < 0.05) the apoptotic (Caspase 3 and Caspase 9) and antimicrobial (ß defensin 1 and 2) genes, but downregulated (P < 0.05) antiapoptotic (B-cell lymphoma 2) and inflammatory (E3 ubiquitin-protein ligase CBL-B) genes at the mRNA and/or protein level in AFB1 supplementation groups. Additionally, Se deficiency downregulated (P < 0.05) GPX3, thioredoxin reductase 1 (TXNRD 1), GPX4, and selenoprotein (SELENO) S, and upregulated (P < 0.05) SELENOT and SELENOU in spleen in AFB1 administered groups. CONCLUSIONS: Dietary Se deficiency exacerbated AFB1-induced spleen injury in chicks, partially through the regulation of oxidative stress, inflammatory and apoptotic signaling, and 6 selenoproteins.

Novel distance-progesterone-combined selection approach improves human sperm quality.

BACKGROUND: Sperm selection is essential for the health of offspring conceived via assistive reproductive technology (ART). Various methods of sperm preparation for in vitro fertilization and intracytoplasmic sperm injection have been developed to acquire sperm with better quality and to avoid potential genetic disorders. However, current sperm processing and selection techniques bypass the natural selection that occurs during fertilization in vivo. The aim of this study was to present a novel distance-progesterone-combined selection approach with an original device based on the human female reproductive tract, and to report on its effectiveness based on sperm progressive motility, as well as chemotaxis. METHODS: A novel device with long distance channels which mimicked the female human reproductive system was designed and fabricated. This ready-to-be-used device was developed using a progesterone gradient and human tube fluid media. Sperm swam for 150 min in the device under conditions of 37 °C air temperature with 5% CO2 after separation from seminal plasma via discontinuous Percoll gradient treatment. The selected sperm were assessed for normal morphology using Diff-Quik staining. A chromatin diffusion assay assessed sperm for DNA fragments and apoptosis was assessed using annexin V-fluorescein isothiocyanate/propidium iodide fluorescent staining. RESULTS: Our distance-progesterone-combined sperm selection method was successfully established. After sperm were selected, the percentage of sperm with normal morphology increased (before vs. after selection, 11.2 ± 1.3% vs. 40.3 ± 6.6%, P = 0.000), the percentage of sperm with DNA fragmentation decreased (before vs. after selection, 15.4 ± 4.0% vs. 6.8 ± 3.3%, P = 0.001), and the percentage of sperm with apoptosis did not change significantly. CONCLUSIONS: Our newly-developed method is capable of successfully selecting sperm of high quality. The method will be benefit clinical ART practice as it can reduce sperm-related genetic risks.

Dietary Silymarin Supplementation Alleviates Zearalenone-Induced Hepatotoxicity and Reproductive Toxicity in Rats.

Background: Zearalenone (ZEN) can cause serious defects in development and reproduction in humans and animals. Silymarin shows antioxidant and estrogenic effects. Objective: This study was conducted to determine if silymarin can antagonize ZEN-induced hepatic and reproductive toxicities. Methods: Thirty-five 21-d-old female Sprague-Dawley rats (n = 7/diet) were fed a control diet (Ctrl) or Ctrl plus 20 mg ZEN/kg or Ctrl plus 20 mg ZEN/kg with 100, 200, or 500 mg silymarin/kg for 6 wk. Serum, livers, ovaries, and uterus were collected at week 6 for biochemistry, hormone, and redox status and selected gene and protein assays. Results: The consumption of ZEN decreased (P < 0.05) the final body weight by 17.9%, induced liver injury, increased (P < 0.05) aspartate aminotransferase and alkaline phosphatase activities, and decreased (P < 0.05) total protein and albumin concentrations in serum by 16.7-40.6%. ZEN also caused reproductive toxicity, including decreased (P < 0.05) 17ß-estradiol and increased (P < 0.05) follicle-stimulating hormone concentrations in serum by 12.7-46.3% and induced histopathologic alterations in the liver, ovaries, and uterus. Interestingly, these alterations induced by ZEN were alleviated (P < 0.05) by silymarin supplementation at 100, 200, and 500 mg/kg. Moreover, silymarin supplementation at the 3 doses mitigated (P < 0.05) ZEN-induced impairment in hepatic glutathione peroxidase activity, total antioxidant capacity, and malondialdehyde concentration by 17.6-100%. Meanwhile, silymarin supplementation at all doses upregulated (P < 0.05) phospho-ribosomal protein S6 kinase 1 (p-RPS6KB1) and 3ß-hydroxysteroid dehydrogenase (HSD3B) by 43.0-121% but downregulated (P < 0.05) AMP-activated protein kinase (AMPK) and 3α-hydroxysteroid dehydrogenase (HSD3A) in the liver relative to the ZEN group by 11.2-40.6%. In addition, silymarin supplementation at all doses elevated (P < 0.05) HSD3B by 1.8- to 2.5-fold and decreased (P < 0.05) estrogen receptor 1 (ESR1), ATP binding cassette (ABC) c1, and Abcc5 in ovaries and the uterus by 10.7-63.2%. Conclusion: Dietary silymarin supplementation at 100, 200, and 500 mg/kg protected rats from ZEN-induced hepatotoxicity and reproductive toxicity, potentially through improvement in the antioxidant capacity and regulation in the genes related to protein synthesis, ZEN metabolism, hormone synthesis, and ABC transporters in the tissues.

Controllable Fluorescence Switching of a Coordination Chain Based on the Photoinduced Single-Crystal-to-Single-Crystal Reversible Transformation of a syn-[2.2]Metacyclophane.

The observation of a reversible chemical transformation corresponding to an external stimulus in the solid state is intriguing in the exploration of smart materials, which can potentially be applied in molecular machines, molecular switches, sensors, and data storage devices. The solid-state photodimerization reaction of 1,3-bis[2-(4-pyridyl)ethenyl]benzene (1,3-bpeb) in a one-dimensional coordination polymer {[Cd2(1,3-bpeb)2(4-FBA)4]·H2O}n (4-FBA = 4-fluorobenzoate) with 365 nm UV light afforded syn-tetrakis(4-pyridyl)-1,2,9,10-diethano[2.2]metacyclophane (syn-tpmcp) in quantitative yield via a single-crystal-to-single-crystal (SCSC) transformation. Upon irradiation with 254 nm UV light, an SCSC conversion from syn-tpmcp to 1,3-bpeb was also achieved in quantitative yield within the syn-tpmcp-supported coordination polymer {[Cd2(syn-tpmcp)(4-FBA)4]·H2O}n. In particular, accompanied by the reversible transformation between 1,3-bpeb and syn-tpmcp, the coordination chain exhibits photocontrollable fluorescence-switching behavior, which makes this intelligent material an appealing candidate for practical applications.