Calcineurin suppresses rat H9c2 cardiomyocyteprotective autophagy under chronic intermittent hypoxia by downregulating the AMPK pathway.

Calcineurin plays a key role in cardiovascular pathogenesis by exerting pro-apoptotic effects in cardiomyocytes. However, whether calcineurin can regulate cardiomyocyte autophagy under conditions of chronic intermittent hypoxia (CIH) remains unclear. Here, we showed that CIH induced calcineurin activity in H9c2 cells, which attenuated adenosine monophosphate-activated protein kinase (AMPK) signaling and inhibited autophagy. In H9c2 cells, autophagy levels, LC3 expression, and AMPK phosphorylation were significantly elevated under conditions of CIH within 3 days. However, after 5 days of CIH, these effects were reversed and calcineurin activity and apoptosis were significantly increased. The calcineurin inhibitor 17-Allyl-1,14-dihydroxy-12-[2-(4-hydroxy-3-methoxycyclohexyl) -1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo- [22.3.1.04,9]octacos-18- ene-2,3,10,16-tetrone (FK506) restored AMPK activation and LC3 expression and attenuated CIH-induced H9c2 cell apoptosis. In contrast, calcineurin overexpression significantly attenuated the increase in LC3 expression and enhanced H9c2 cell apoptosis under conditions of CIH. Calcineurin inhibition failed to induce autophagy or alleviate apoptosis in H9c2 cells expressing a kinase-dead K45R AMPK mutant. Autophagy inhibition abrogated the protective effects of FK506-mediated calcineurin inhibition. These results indicate that calcineurin suppresses adaptive autophagy during CIH by downregulating AMPK activation. Our findings reveal the underlying mechanism of calcineurin and autophagy regulation during H9c2 cell survival under conditions of CIH and may provide a new strategy for preventing CIH-induced cardiomyocyte damage.

An Overview of Naphthylimide as Specific Scaffold for New Drug Discovery.

Naphthylimides play a pivotal role as aromatic heterocyclic compounds, serving as the foundational structures for numerous pharmacologically significant drugs. These drugs encompass antibacterial, antifungal, anticancer, antimalarial, antiviral, anti-inflammatory, antithrombotic, and antiprotozoal agents. The planar and heteroaromatic characteristics of naphthylimides grant them a strong ability to intercalate into DNA. This intercalation property renders naphthylimide derivatives highly valuable for various biological activities. The advantageous pharmacological activity and ease of synthesis associated with naphthylimides and their derivatives provide significant benefits in the design and development of new compounds within this class. Currently, only a few such molecules are undergoing preclinical and clinical evaluations. In this paper, we have compiled the literature on naphthylimides reported by researchers from 2006 to 2024. Our focus lies on exploring the pharmacological activities of their analogues from a drug development and discovery perspective, while examining their structure-activity relationship and mechanisms of action.

CircDNAJC11 interacts with TAF15 to promote breast cancer progression via enhancing MAPK6 expression and activating the MAPK signaling pathway.

BACKGROUND: Breast cancer (BC) is a common malignant tumor in women worldwide. Circular RNA (circRNA) has been proven to play a critical role in BC progression. However, the exact biological functions and underlying mechanisms of circRNAs in BC remain largely unknown. METHODS: Here, we first screened for differentially expressed circRNAs in 4 pairs of BC tissues and adjacent non-tumor tissues using a circRNA microarray. Functionally, gain- and loss-of-function experiments in vitro and in vivo showed that circDNAJC11 promoted BC cell proliferation, migration, invasion, and tumor growth. Mechanistically, RNA pull-down, mass spectrum, RNA immunoprecipitation, fluorescence in situ hybridization assays, and rescue experiments were executed. RESULTS: We found that circDNAJC11 was significantly upregulated in triple-negative breast cancer tissues and cells. Clinical data revealed that the high expression of circDNAJC11 was closely correlated with a poor prognosis of BC patients and could be an independent risk factor for BC prognosis. Functionally, gain- and loss-of-function experiments in vitro and in vivo showed that circDNAJC11 promoted BC cell proliferation, migration, invasion, and tumor growth. Mechanistically, RNA pull-down, mass spectrum, RNA immunoprecipitation, fluorescence in situ hybridization assays, and rescue experiments were executed. We demonstrated that circDNAJC11 combined with TAF15 to promote BC progression via stabilizing MAPK6 mRNA and activating the MAPK signaling pathway. CONCLUSIONS: The circDNAJC11/TAF15/MAPK6 axis played a crucial role in the progression and development of BC, suggesting that circDNAJC11 might be a novel biomarker and therapeutical target for BC.

Elevated PGT promotes proliferation and inhibits cell apoptosis in preeclampsia by Erk signaling pathway.

Prostaglandins participate in maternal recognition of pregnancy, implantation and maintenance of gestation. Prostaglandin transporter (PGT), as a candidate molecule of prostaglandin carriers, might be involved in the pathogenesis of preeclampsia. In preeclampsia (PE) patients' placental tissue, we identified PGT by RNA sequencing, measured its expression pattern by quantitative real-time PCR and Western blot. PGT was found to be upregulated in preeclamptic placental tissue. The expression pattern of PGT in PE was double confirmed by eight Gene Expression Omnibus (GEO) databases. In abortion tissues at 6-8 weeks, we then observed the cellular location of PGT by Immunofluorescence technique (IF) and found PGT located in trophoblast cell of the placenta of early pregnancy. In vitro studies revealed that forced expression of PGT in HTR8/Sveno cell inhibited its apoptosis, but promoted its proliferation by activating Erk signaling. In vivo study, we used reduced uterine perfusion pressure (RUPP) rat model and L-NAME-induced preeclampsia-like rats to study the possible role of PGT in preeclampsia. And PGT was found to be upregulated in both preeclampsia rat models by Immunohistochemical (IHC) staining. Newly identified PGT plays an important role in trophoblast proliferation via Erk signaling, providing new insights for understanding the pathogenesis of PE.

Coffee Grounds-Doped Alginate Porous Materials for Efficient Solar Steam Generation.

Solar steam generation (SSG) devices have emerged as one of the promising technologies for seawater desalination to meet the worldwide demand for clean water. Herein, we fabricated a new monolithic SSG system derived from waste coffee grounds (CG) through a simple carbonization followed by a freeze-drying process (named as CCGA). The as-prepared CCGA possesses a porous structure with superhydrophilic, abundant porosity (81.7%); low thermal conductivity (0.129 W m-1 K-1) in a wet state; low apparent density (25 mg cm-3); and broad sunlight absorption in a wet state (ca. 93%). The combination of its carbon nature and abundant porous structure endowed barrier-free water transmission channels, a self-floating property, and a superb photothermal conversion performance to the SSG. The temperature of the CCGA's upper surface can reach up to 42.6 °C under 1 sun irradiation, and for pure water, the evaporation rate of CCGA can be up to 1.486 kg m-2 h-1, corresponding to a good photothermal conversion efficiency of 86.96%. It also exhibits an excellent desalination capability; e.g., the photothermal conversion efficiency of CCGA in NaCl (20 wt %) brine is measured to be 75.77% under 1 sun irradiation, and the fresh water obtained from artificial seawater can achieve the WHO's standard for domestic water. With the advantages of low cost and a simple preparation process, such biomass-based CCGA materials may have great potential as an efficient SSG device for seawater desalination.

Porphyrin-Based Conjugated Microporous Polymers for Highly Efficient Adsorption of Metal Ions.

The capture and elimination of anions and cations from water have attracted a great deal of attention and are quite vital for clean production and environmental remediation. In this work, we present the synthesis of four porphyrin (Por)-based conjugated microporous polymers (CMPs, namely, Por-CMP-1-4), which were produced through a Sonogashira-Hagihara linked response using porphyrin and acetylene aromatic compounds as building blocks and used as absorbents to eliminate metal ions from water. The as-synthesized Por-CMP-1-4 exhibit an amorphous porous structure and outstanding caloric and physicochemical properties. Taking advantage of their larger specific surface areas, i.e., 541.47, 614.58, 382.38, and 677.90 m2 g-1 for Por-CMP-1-4, respectively, and their chelating active site that originated from the porphyrin ring, Por-CMP-1-4 show better Zn2+, Cu2+, and Pb2+ adsorption ability. Among them, Por-CMP-3 has the greatest adsorbability of 640 mg g-1 for Zn2+, with an adsorption efficiency of 80%, whereas its adsorption capacities for Cu2+ and Pb2+ ions were both 334 mg g-1, with an adsorption efficiency of 42% for Cu2+ and Pb2+. Employing Por-CMP-3 as a representative example, its adsorption kinetics has been systematically investigated. The adsorption behavior of Por-CMP-3 with respect to the Zn2+ ion is shown to exhibit pseudo-first-order kinetics and Langmuir isotherm modes. Meanwhile, the adsorption mechanism is discussed in detail, and it was thought it might be chelation, in which the nitrogen atoms with a single pair of electrons on the porphyrin ring interacted with metal ions to form stable chelation coordination bonds, thus removing metal ions selectively and effectively. Furthermore, Por-CMP-3 exhibited good reusability, retaining 60% of its Zn2+ removal rate after four continuous adsorptions.

Expression and Clinical Significance of KLRG1 and 2B4 on T Cells in the Peripheral Blood and Tumour of Patients with Cervical Cancer.

BACKGROUND: Killer cell lectin-like receptor G1 (KLRG1) and 2B4 play important roles in the immune regulation and immune tolerance to tumor cells by inhibiting T cell function. However, the clinical relevance of KLRG1 and 2B4 to cervical cancer remains to be understood. METHODS: We measured the frequency of KLRG1+ or 2B4+ cells in CD4+ or CD8 + T cells derived from peripheral blood or tumour biopsies in cervical cancer patients by flow cytometry. RESULTS: Compared with healthy controls, the level of KLRG1 and 2B4 on CD8 + T cells in the blood of the patients increased significantly (P = .0056 and .0441). KLRG1 level on CD8 + T cells and 2B4 level on CD4 + T cells in peripheral blood were significantly higher than in tumor tissues (P < .0001 and P = .0003). Higher KLRG1 level on blood-derived CD8 + T cells was observed in patients older than 54 years (P = .001) or tested to be HPV-negative (P = .026). Tumor-infiltrated CD8 + T cells demonstrated elevated KLRG1 level in patients having pelvic lymph node metastasis (P = .016). Increased 2B4 level on blood-derived CD8 + T cells was also observed in patients older than 54 years (P < .001). KLRG1 expression on both CD4 + T (P = .0158) and CD8 + T (P = .0187) cells in the peripheral blood increased after radiotherapy. CONCLUSION: KLRG1 level on T cells was related to age and HPV in patients with cervical cancer, while 2B4 level on T cells was related to age, underlying their roles in the host immune response to cervical cancer. Radiotherapy can improve the immune function of patients.

Discovery of novel 4-arylamino-quinazoline derivatives as EGFRL858R/T790M inhibitors with the potential to inhibit the non-small cell lung cancers.

Three series of quinazoline derivatives (7a-j, 8a-o, 9a-l) were designed and synthesized as EGFRL858R/T790M inhibitors. Series 7a-j and 8a-o are urea and thiourea derivatives while category 9a-l contain the Michael receptor active warhead. Most of the compounds exhibited excellent anti-proliferative activity in vitro against several cancer cell lines, including non-small cell lung cancer (NSCLC) cell lines A549 and H1975, among which 14 compounds had strong antiproliferative activity against A549 and H1975 cancer cells. What's more, they also showed moderate to excellent kinase inhibitory activity against EGFRWT and EGFRL858R/T790M. 8o exhibited the best kinase inhibitory activity with IC50 values of 0.8, 2.7 nM against EGFRWT and EGFRL858R/T790M, respectively. Moreover, AO single staining and Annexin V-FITC/PI staining results also indicated that both 8o and 9b significantly induced apoptosis in A549 cells. 8o arrested the cell cycle at S phase and 9b arrested the cell cycle at G1 phase.

A large-scale study reveals 24-h operational rhythms in hospital treatment.

Hospitals operate 24 h a day, and it is assumed that important clinical decisions occur continuously around the clock. However, many aspects of hospital operation occur at specific times of day, including medical team rounding and shift changes. It is unclear whether this impacts patient care, as no studies have addressed this. We analyzed the daily distribution of ∼500,000 doses of 12 separate drugs in 1,546 inpatients at a major children's hospital in the United States from 2010 to 2017. We tracked both order time (when a care provider places an electronic request for a drug) and dosing time (when the patient receives the drug). Order times were time-of-day-dependent, marked by distinct morning-time surges and overnight lulls. Nearly one-third of all 103,847 orders for treatment were placed between 8:00 AM and 12:00 PM. First doses from each order were also rhythmic but shifted by 2 h. These 24-h rhythms in orders and first doses were remarkably consistent across drugs, diagnosis, and hospital units. This rhythm in hospital medicine coincided with medical team rounding time, not necessarily immediate medical need. Lastly, we show that the clinical response to hydralazine, an acute antihypertensive, is dosing time-dependent and greatest at night, when the fewest doses were administered. The prevailing dogma is that hospital treatment is administered as needed regardless of time of day. Our findings challenge this notion and reveal a potential operational barrier to best clinical care.

Demonstration study of bypass multipond wetland system to enhance river water quality.

This study focused on the water quality of a river in Wuhan City, China, which is surrounded by ponds that were transformed into a bypass multipond wetland system to improve river water quality. The bypass multipond wetland system included surface-flow artificial wetlands, modified partition ponds, aeration reoxygenation ponds, ecological ponds, and other processes. After the stable operation of the process, the water transparency was higher than 60 cm and the dissolved oxygen (DO) was higher than 5 mg/L, while the ammonia nitrogen (NH3-N) concentration was less than 1.0 mg/L, total phosphorus (TP) was lower than 0.2 mg/L, and chemical oxygen demand (COD) was lower than 20 mg/L, achieving the treatment target. After monitoring the results of each process, the process which best enhanced the water transparency enhancement was the surface-flow of the artificial wetlands and ecological ponds. The aeration reoxygenation pond had the best effect on DO enhancement. The processes that most affected NH3-N and TP removal were the surface-flow artificial wetlands and ecological ponds. The modified parthenogenic pond had the greatest effect on COD removal. The bypass multipond wetland system not only improved the river water quality but also enhanced the river landscape, and can act as a reference for similar river water quality improvement actions.

Perinatal Transmission of 2019 Coronavirus Disease-Associated Severe Acute Respiratory Syndrome Coronavirus 2: Should We Worry?

We present 2 cases of coronavirus disease 2019 (COVID-19)-associated severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the third trimester of pregnancy. Both mothers and newborns had excellent outcomes. We failed to identify SARS-CoV-2 in all of the products of conception and the newborns. This report provided evidence of low risk of intrauterine infection by vertical transmission of SARS-CoV-2.

Case series of 20 pregnant women with 2019 novel coronavirus disease in Wuhan, China.

AIM: To evaluate perinatal outcomes regarding clinical presentation in pregnancy and the vertical transmission potential of COVID-19. METHODS: Clinical records, laboratory findings, and chest computed tomography (CT) scans were retrospectively reviewed from 20 pregnant patients with laboratory-confirmed COVID-19 who were admitted to Renmin Hospital of Wuhan University and The Third Hospital of Wuhan, from Jan 20 to Mar 16, 2020, including three in the first-trimester, two in the second-trimester, and 15 in the third-trimester. Evidence of vertical transmission was assessed by testing for neonatal throat swab samples. The pathological changes of COVID-19 on the placenta is evaluated by hematoxylin-eosin staining. RESULTS: The most common symptoms of the pregnant women with SARS-CoV-2 infection were fever and cough, which is comparable to the nonpregnant adults with COVID-19 infection. Nobody was transferred to intensive care unit (ICU) for treatment and there were no maternal and neonatal deaths. However, there was one case with induced abortions on first-trimester (due to pregnant woman's concerns about COVID-19), one diagnosed with ectopic pregnancy, no intrauterine fetal deaths during the study period. Delivery occurred in 15 patients in the third trimester. Their incidence of preterm birth was 20%. Three of the four preterm births were spontaneous. The average length of stay was 20.77 days. No neonatal SARS-CoV-2 infection was detected. There were two placentas found with acute chorioamnionitis, one showed normal placenta morphology. CONCLUSION: In this case series study, COVID-19 had no short-term adverse effect on pregnant women except premature birth. The vertical transmission of SARS-CoV-2 did not occur in our study.

Effects of resveratrol on reducing spermatogenic dysfunction caused by high-intensity exercise.

BACKGROUND: Long-term high-intensity exercise can lead to reproductive endocrine and spermatogenic dysfunction. This research is to investigate the effect of resveratrol on the reduction of reproductive dysfunction induced by high-intensity exercise, and to screen relevant factors and signal transduction pathways. METHODS: Rats were randomly divided into three groups, a control group, an intensive exercise group (IE group), and a resveratrol-treated group (RSV group). After 9 weeks of exercise, the sperm density and reproductive hormone concentrations were measured, along with antioxidation, inflammatory cytokine production, and histological analyses performed for each group. In addition, a proteomics analysis of the IE group and RSV group were conducted. RESULTS: We found that compared with the control group, the average sperm density (P < 0.05) and testosterone concentration (P < 0.05) in the IE group decreased significantly. Additionally, in testis tissue the concentration of the inflammatory cytokines IL-6 (P < 0.01) and TNF-α (P < 0.01) increased significantly. Also, a significant decrease in superoxide dismutase (SOD) activity (P < 0.01) and a significant increase in the malondialdehyde (MDA) concentration (P < 0.01) were noted. In the RSV group, the average sperm density (P < 0.01), testosterone (P < 0.01) and follicle stimulating hormone (FSH) levels (P < 0.01) all increased in comparison to the IE group, and the concentration of IL-6 (P < 0.01) and TNF-α (P < 0.01) were found to be significantly decreased. Compared with the IE group, the SOD activity in the RSV group was significantly increased (P < 0.01), while the MDA content decreased (P < 0.01). Furthermore, histological analysis showed that the number of spermatogenic epithelial cells in the RSV group was higher than that of the IE group. There were a number of spermatogenic regulatory proteins identified in the proteomics analysis, including Clusterin, Piwi like homolog 1 (Piwil1), Zona pellucida binding protein (Zpbp), Heat shock-related 70 kDa protein 2 (Hspa2), Centrin 1, and Bardet-Biedl syndrome 2 protein (Bbs2). It was found that the proteins that differed between the two groups were mainly involved in pathways such as complement and coagulation cascades, the extracellular matrix-receptor interactions, etc. CONCLUSIONS: The present study demonstrates that after high-intensity exercise, the inflammatory cascade in the tissue of the testis increases with decreased resistance to oxidation and disordered spermatogenic function. Resveratrol can improve the reproductive dysfunction of rats that was induced by high-intensity exercise. It mostly promotes reproductive function by increasing testosterone secretion, reducing the inflammatory response, improving the antioxidant capacity, affecting the expression of spermatogenic regulatory proteins, and enhancing the signal transduction pathway of spermatogenesis.

Diagnostic value of multimodal ultrasound imaging in differentiating benign and malignant TI-RADS category 4 nodules.

BACKGROUND: Differential diagnosis of benign and malignant thyroid imaging reporting and data system category 4 (TI-RADS-4) nodules can be difficult using conventional ultrasound (US). This study aimed to evaluate whether multimodal ultrasound imaging can improve differentiation and characterization of benign and malignant TI-RADS-4 nodules. METHODS: Multimodal ultrasound imaging, including US, superb microvascular imaging (SMI), and real-time elastography (RTE), were performed on 196 TI-RADS-4 nodules (78, benign; 118, malignant) in 170 consecutive patients. The sensitivity, specificity, accuracy, false negative rate (FNR), and false positive rate (FPR) of each single method and that of multimodal US imaging were determined by comparison with surgical pathology results. RESULTS: The sensitivity, specificity, accuracy, FNR, and FPR for US were 65.25%, 69.23%, 66.84%, 34.75%, 30.77%, respectively; for SMI were 77.97%, 93.59%, 84.18%, 22.03%, 6.41%, respectively; RTE, 80.51%, 84.62%, 82.14%, 19.49%, 15.38%; and for multimodal US imaging were 94.08%, 87.18%, 91.33%, 6.93%, 12.82%, respectively. The areas under the received operating characteristic curve for US, SMI, RTE, and multimodal US imaging in evaluating benign and malignant TI-RADS-4 nodules were 67.2%, 84.40%, 86.60%, and 95.50%, respectively. CONCLUSIONS: The initial clinical results suggest that multimodal US imaging improves the diagnostic accuracy of TI-RADS-4 nodules and provides additional information for differentiating malignant and benign nodules.

Association between left ventricular ejection fraction and Kawasaki disease shock syndrome.

OBJECTIVE: This study was performed to explore the clinical features of Kawasaki disease shock syndrome and analyse the association between the left ventricular ejection fraction and Kawasaki disease shock syndrome. METHODS: We retrospectively reviewed the medical records of all consecutive inpatients with Kawasaki disease at Wenzhou Medical University Second Affiliated Hospital and Yuying Children's Hospital in Wenzhou, China from January 2009 to December 2016. We compared the clinical characteristics, laboratory data, and left ventricular ejection fraction between patients with and without Kawasaki disease shock syndrome and analysed the effect of the left ventricular ejection fraction on Kawasaki disease shock syndrome under different clinical conditions of Kawasaki disease. RESULTS: In total, 1147 patients were diagnosed with Kawasaki disease. Of these 1147 patients, 17 were diagnosed with Kawasaki disease shock syndrome; 68 patients admitted to the hospital at the same time, ±2 weeks, with Kawasaki disease but without Kawasaki disease shock syndrome served as the control group. Compared with the control group, the Kawasaki disease shock syndrome group had a significantly higher incidence of coronary artery lesions, cardiac troponin I concentration, N-terminal prohormone of brain natriuretic peptide concentration, neutrophil count and ratio, alanine aminotransferase concentration, aspartate aminotransferase concentration, and C-reactive protein concentration and a significantly lower platelet count, serum albumin concentration, and left ventricular ejection fraction. A low left ventricular ejection fraction was associated with Kawasaki disease shock syndrome under different conditions of Kawasaki disease. CONCLUSION: Among patients with Kawasaki disease, cardiac injury is more likely in those with Kawasaki disease shock syndrome than without, and a low left ventricular ejection fraction may be associated with the development of Kawasaki disease shock syndrome.

Proteomics analysis of intensive exercise-induced disorders of gametogenesis in the testis using isobaric tags for relative and absolute quantification (iTRAQ) analysis.

In the present study we screened a panel of regulatory proteins associated with gametogenesis disorders in the testis that are induced by intensive exercise. Four-week-old Sprague-Dawley male rats were randomly divided into three groups: a control group, a no-load exercise group and an intensive exercise group. Rats in the control group were free to move in their cage. Rats in the no-load exercise and intensive exercise groups swam for 60minday-1, six times each week, for a total 9-week exercise regimen; rats in the intensive exercise group swam with a load of 6% body mass. After the last exercise session (or at the end of the 9-week period), a sperm count, reproductive hormone assays, histological analysis of the testis and proteomics analysis were performed for each rat. Mean (±s.d.) sperm concentration was significantly lower in the intensive exercise group than in the control and no-load exercise groups (1.36±0.63 vs 2.12±0.53 and 2.57±0.48×106 spermatozoa mL-1 respectively; P<0.05). Serum testosterone concentrations were also significantly lower in the intensive exercise group (P<0.01), whereas gonadotrophin-releasing hormone, LH and FSH concentrations were slightly decreased in the intensive exercise group, but not significantly (P>0.05). Histological analysis showed that the number of spermatogenic cells in the seminiferous tubules was lower in the intensive exercise group than in the control and no-load exercise groups. Proteomics analysis identified 54 proteins that were differentially expressed between the control and intensive exercise groups (31 downregulated, 23 upregulated). Pathway enrichment analysis showed that ribosome and extracellular matrix-receptor interaction pathways play an important role in the signal transduction of testicular gametogenic disorders. Four differentially expressed proteins that were involved in the regulation of reproduction were identified by bioinformatics analysis and validated by targeted mass spectrometry analysis, namely vimentin, collagen α-1(I) chain, fatty acid-binding protein 9 and 40S ribosomal protein S3a. The data suggest that changes in the abundance of differentially expressed proteins after long-term intensive exercise affect the cycle and progression of spermatogenesis, resulting in spermatogenic disorders.

[Aerobic exercise improves spermatogenesis of male rats: Results of iTRAQ-based proteomic analysis of the testis tissue].

OBJECTIVE: To investigate the effect of aerobic exercise on the spermatogenic function of male rats and screen out differentially expressed proteins related to spermatonesis-regulation by proteomic analysis. METHODS: We randomly divided 24 SD male rats into groups A (non-exercise control), B (exercise), and C (weight-bearing exercise), those in the latter two groups made to swim for 60 minutes a day and those in group C bearing a load 3% of the body weight, both 6 times a week for 9 weeks. At 24 hours after the last exercise, we obtained the sperm count, measured the levels of such serum reproductive hormones as testosterone (T), luteotrophic hormone (LH), follicle-stimulating hormone (FSH), and gonadotrophin-releasing hormone (GnRH), and employed isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis of the testicular tissue. RESULTS: Compared with group A, group C showed significant increases in sperm concentration (ï¼»2.12 ± 0.43ï¼½ vs ï¼»3.54 ± 0.52ï¼½ ×106/ml, P <0.01) and the levels of serum LH (ï¼»35.99 ± 2.90ï¼½ vs ï¼»38.96 ± 1.34ï¼½ IU/L, P <0.01) and T (ï¼»19.99 ± 0.25ï¼½ vs ï¼»21.36 ± 0.53ï¼½ nmol/L, P <0.01), but no statistically significant differences in GnRH (ï¼»623.95 ± 41.44ï¼½ vs ï¼»641.82 ± 42.78ï¼½ ng/L, P >0.05) and FSH (ï¼»20.49 ± 2.44ï¼½ vs ï¼»22.29 ± 2.31ï¼½ IU/L, P >0.05). No significant changes were observed in sperm concentration or reproductive hormone levels in group B as compared with A. Group B exhibited obviously more mature sperm and cell layers in the seminiferous epithelium than group A. A total of 47 differentially expressed proteins were identified, of which 37 were up-regulated and the other 10 down-regulated. In addition, another 5 significantly differentially expressed proteins closely related to reproductive function were identified, including up-regulated Anx A1, GPX3, Rimbp3, and Dpy19l2 and down-regulated CYP17. Enrichment analysis showed that the differentially expressed proteins were mainly involved in extracellular matrix-receptor interaction, protein digestion and absorption, and focal adhesion pathways. CONCLUSIONS: Proper-intensity exercise can improve the spermatogenic function of rats. Aerobic exercise promotes spermatogenesis mainly by up-regulating the expressions of the proteins related to the production and differentiation of spermatozoa.

Collaborative Testing in Practical Laboratories: An Effective Teaching-Learning Method in Histology.

This article presents an experimental teaching and learning program used in histology with first-year students in the second term in the Faculty of Biology at Huanghuai University, China. Eighty-six students were divided randomly into two groups (n=43 per group). Tests were conducted at the end of each practical laboratory (10 laboratories in total) in which collaborative testing was used in the experimental group and traditional testing in the control group. To assess achievement, a final examination in histology was carried out at the end of the course. To determine students' attitude to the teaching styles, a questionnaire survey was conducted at the end of the term. Results showed that students preferred the collaborative testing format. In the experimental group, students' scores were significantly higher than those of students in the control group in final examinations. These findings indicate that collaborative testing enhances student learning and understanding of the material taught, and suggest that collaborative testing is an effective teaching-learning method in histology.

Effect of resveratrol on restoring spermatogenesis in experimental cryptorchid mice and analysis of related differentially expressed proteins.

The present study aimed to evaluate the effect of trans-Resveratrol on spermatogenesis. Male Kunming suckling mice (10 days old) were surgically rendered cryptorchid and subcutaneously injected with trans-Resveratrol at doses of 5, 10, 20, and 40 µg/g/day as groups I, II, III, and IV, respectively, for 35 days. Animals in the control group received 10 µL/mouse/day of olive oil. Serum estradiol, testosterone, FSH, and LH levels were measured on day 45. Tissue analysis and sperm morphological abnormalities analysis were done. Results showed that in the control group and group I only spermatogonia and primary spermatocytes were present, whereas spermatogenesis was totally restored in groups II, III, and IV. Sperm counts in groups III and IV were remarkably higher than the control group (P<0.05). The morphological abnormalities in resveratrol-treated groups were higher than the mature mice. Serum estradiol levels in the resveratrol-treated groups were not significantly different from the control group, but were lower than the mature mice (P<0.05). There was no significant difference in serum testosterone levels between the resveratrol-treated groups and mature mice, but the levels in the resveratrol-treated groups was significantly lower than the control group (P<0.05). No significant influence of trans-Resveratrol was observed on serum FSH levels in all cryptorchid mice. Serum LH levels in groups I, II, and III were higher than the control group. These results indicate that trans-Resveratrol restores spermatogenesis in cryptorchid mice. In addition, proteomic analysis between the 20 µg/g/day resveratrol-treated group and the control group was carried out, and five kinds of proteins (BAF250, ZFP261, CHD1L, RBBP9, and SOHLH2) were identified. The expression of SOHLH2 increased, while that of BAF250, ZFP261, CHD1L, and RBBP9 decreased in the 20 µg/g/day resveratrol-treated group, indicating that SOHLH2 may contribute to testicular germ cell differentiation.

Collaborative quiz-based teaching strategy in histology.

In the present article we introduce a teaching strategy used in a histology course with first-year students in the first term of their studies at the Faculty of Veterinary Medicine at Huanghuai University, China. Forty students were randomly divided into two sections (n=20/section). Students in the first section were taught using a collaborative quiz-based strategy (the experimental section), and students in the second section were taught using a traditional teaching strategy (the control section). To assess achievement of learning, a final examination was carried out at the end of the course. To determine students' attitudes toward the teaching strategy used, a questionnaire was conducted at the end of the term. Results showed that students preferred the collaborative quiz-based teaching strategy. The final-examination scores of students in the experimental section were significantly higher than those of students in the control section (p<.05), which indicates that the collaborative quiz-based strategy results in better performance on examinations compared to the traditional histology course.