MO Group Research Articles

Role of molybdenum in ameliorating busulfan-induced infertility in female mice

BackgroundMolybdenum (Mo) plays a crucial role in regulating normal physiological function. However, its potential effect on female infertility has received little attention. MethodsIn this study, we explored the potential molecular mechanisms of Mo’s action on mouse ovaries and oocytes by establishing a busulfan-induced infertility model. Adult female Kunming mice were randomly divided into three groups: control, +busulfan, and +busulfan+Mo. After 30 days of busulfan treatment [Myleran, 20 mg/kg body weight ip], mice in the busulfan+Mo group were provided with 7.5 mg/L Mo per day in drinking water for an additional 42 days. On day 72, we examined the morphology of the oocytes and ovarian tissue after H&E staining, measured the concentrations of serum hormones by ELISA, and detected Bax, Bcl-2, caspase-3 and caspase-9 by immunohistochemical staining and western immunoblotting. We also assessed the oxidative stress in cells by measuring the activity of the antioxidant enzyme, SOD, the concentrations of MDA and LDH, and the percentage of apoptotic cells using kits. The number of litters born was counted after mating with male mice, and the organ coefficients were calculated after weighing on an analytic balance. ResultsResults showed that Mo treatment restored female reproductive hormone levels to near normal. Mo also significantly inhibited the mitochondrial stress-induced expression of apoptotic proteins. ConclusionOur findings demonstrate that Mo treatment at a dose of 7.5 mg/L can ameliorate busulfan-induced infertility in female mice. These data may provide a reference for the development of treatments for female infertility.

Positive effects of a mixture of fish oil and soybean oil as a dietary lipid source on the ovarian development and health of female giant river prawn, Macrobrachium rosenbergii broodstock

Lipids are key nutrients that affect the development of the ovary in aquatic animals. This study aimed to investigate the effects of different lipid sources on the ovarian development and health of Macrobrachium rosenbergii broodstock. The M. rosenbergii broodstock, with an initial body weight of 8.07±0.74 g, were fed diets containing 5 % fish oil (FO), soya bean oil (SO), rapeseed oil (RO), coconut oil (CO), and a 1:1 mixture of fish oil and soybean oil (MO) as lipid sources for a period of 56 days. The results indicated that there were no significant differences in survival rate (SR) and hepatopancreatic index (HSI) among the different groups (P > 0.05). However, the specific growth rate (SGR) and gonadosomatic index (GSI) in the MO group were significantly higher than other groups (P < 0.05). Additionally, fatty acid levels in diets directly influenced the fatty acid composition of prawn hepatopancreas, showing a similar trend to that observed in the diet itself. Furthermore, compared to the other trial groups, haemolymph levels of 17-β estradiol (E2) and progesterone (PROG) were significantly increased in the MO group (P < 0.05). The ovarian section also exhibited better histomorphology and larger oocyte diameter in this group. Moreover, total antioxidant capacity was significantly increased in the MO group (P < 0.05). Saturated fatty acids in RO and CO groups could promote the expression of lipid synthesis-related genes fatty acid synthase (fas) and acetyl-CoA carboxylase (acc), concurrently suppressing the expression of lipid catabolism-related genes acyl-CoA oxidase-1 (acox-1) and AMP-activated protein kinase alpha (ampkα) (P < 0.05). Conversely, polyunsaturated fatty acids in the MO group significantly up-regulated the expression levels of fatty acid binding protein-3 (fabp-3) and peroxisome proliferator-activated receptor gamma (pparγ) (P < 0.05). Based on the findings of hepatopancreatic tissue structure, it was determined that the use of a single vegetable oil resulted in some damage to the hepatopancreatic tissue structure of M. rosenbergii broodstock, leading to increased oxidative stress. In conclusion, it is recommended that a 1:1 mixture of fish oil and soybean oil be used as a dietary lipid source to effectively meet the nutritional requirements during the ovarian development period of M. rosenbergii broodstock. This combination also enhances antioxidant properties, promotes the synthesis of haemolymph steroid hormones and lipid metabolism in female prawns, thereby facilitating ovarian development and overall health of M. rosenbergii broodstock.

Global Leadership Initiative on Malnutrition-defined malnutrition coexisting with visceral adiposity predicted worse long-term all-cause mortality among inpatients with decompensated cirrhosis

Background/objectivesMalnutrition coexisting with abdominal adipose tissue accumulation bring a double burden on prognosis. More recently, the Global Leadership Initiative on Malnutrition (GLIM) has reached a novel consensus concerning the diagnostic criteria, that is, a two-step modality combining nutritional risk screening and subsequent phenotypic/etiologic parameters for comprehensive evaluation in hopes of harmonizing the malnutrition diagnosis. We aimed to elucidate their synergistic impact among inpatients with decompensated cirrhosis concerning long-term mortality.Subjects/methodsMalnutrition, visceral obesity, and visceral adiposity were defined by the Global Leadership Initiative on Malnutrition (GLIM), visceral fat area (VFA), and visceral to subcutaneous adipose tissue area ratio (VSR) on computed tomography, respectively. Accordingly, the patients were categorized into different groups given their nutritional status and visceral obesity/adiposity. Multivariate Cox regression was performed to identify independent risk factors associated with 1-year all-cause mortality. Kaplan–Meier curves with log-rank tests were compared among distinct groups.ResultsTotally, 295 patients were recruited. GLIM, VFA, and VSR identified 131 (44.4%), 158 (53.6%), and 59 (20%) patients with malnutrition, visceral obesity and visceral adiposity, respectively. Malnutrition coexisted with visceral obesity in 55 (MO group) relative to visceral adiposity in 40 patients (MA group). Multivariate Cox analysis showed that MA (hazard ratio: 2.48; 95% confidence interval: 1.06, 5.79; P = 0.036) was independently associated with dire outcome rather than MO. Moreover, patients with cirrhosis in the MA group had the worst survival status when compared with other groups (log-rank test: P < 0.001).ConclusionsThe current study indicated that coexisting GLIM-defined malnutrition and VSR-defined visceral adiposity were in relation to worse long-term mortality among inpatients. It is imperative to delicately manage nutritional status and provide personalized treatment in this vulnerable subgroup for achieving better prognosis.

112 Effects of maternal body condition on colostrum, foal weight, and foal IgG concentration

Abstract Foals are born with little to no immunity and rely on maternal colostrum to develop adequate circulating immunoglobulin G (IgG) concentrations in the periparturient period. Colostrum directly impacts the health of the foal, and there are limited data assessing how maternal metabolism and body condition impacts IgG in colostrum and in the foal postnatally. To determine the influence of maternal body condition score (BCS) and cresty neck score (CNS) on glucose and insulin metabolism in the pregnant mare, colostrum composition, and colostrum and foal IgG concentrations, light breed mares (n = 6) were divided into two groups based on BCS and CNS at 315 ± 0.45 d of gestation. The groups were identified as moderately obese (MO; n = 3, BCS) and lean (LN; n = 3). Mares were fasted overnight and then underwent an intravenous (iv) glucose tolerance test at 315 ± 0.45 d gestation. Blood samples were collected at -30, -15 and 0 min and mares were administered dextrose iv [0.3 g/kg body weight (BW)] over 3.7 ± 0.17 min followed by an intravenous infusion of insulin (0.3 mU/kg BW) 20-min later. Additional blood samples were collected 2, 5, 10, 15, 20, 25, 30, 45, 60, and 120 min after initiation of dextrose infusion. At parturition, a colostrum sample was collected before foals nursed and analyzed for protein and fat, and IgG concentration. A foal blood sample was collected 18 h after birth to determine passive transfer of IgG. Placental, mare, and foal weights were measured at birth. Data were analyzed using a t-test with significance at P ≤ 0.05 and a tendency at 0.05 &amp;lt; P ≤ 0.10. The MO group had greater BCS (P = 0.01) and CNS (P = 0.01) than the LN group. Moderately obese mares tended to have 9% greater glucose area under the curve (AUC) after dextrose (P = 0.10) and a 9% greater glucose AUC after insulin infusion (P = 0.10) than LN mares. Colostrum IgG concentrations, and protein and fat content (P ≥ 0.3) did not differ between groups. Foal serum IgG concentrations, foal BW, and placental weights were similar between groups (P ≥ 0.8). The ratios between foal BW and placenta weight, and between foal BW and mare BW were similar between groups (P ≥ 0.3). Moderately obese maternal BCS and CNS scores may decrease maternal glucose clearance during late gestation but did not impact colostrum quality or foal IgG concentrations within 24 h postpartum. As the equine fetus matures later in gestation than other livestock species and relies heavily on glucose uptake from the placenta, it is critical to increase our understanding of the impacts of maternal obesity and glucose clearance on foal development and pre- and post-natal health.

Effect of orally administered B. subtilis-cNK-2 on growth performance, immunity, gut health, and gut microbiome in chickens infected with Eimeria acervulina and its potential as an alternative to antibiotics

This study investigated the best oral delivery strategy (gavage or feed) for the B. subtilis expressing the chicken anti-microbial peptide cNK-2 (B. subtilis-cNK-2) in comparison to monensin, in chickens challenged with Eimeria acervulina (E. acervulina). A total of 120 broiler chickens were randomly allocated into 5 treatment groups in a completely randomized design: 1) uninfected chickens fed with basal diet (NC), 2) E. acervulina-infected chickens fed a basal diet (PC), 3) E. acervulina-infected chickens fed a basal diet supplemented with 90 mg monensin/kg feed (MO), 4) E. acervulina-infected chickens fed a basal diet and orally gavaged with B. subtilis-cNK-2 at 1 × 1010 cfu/d (CNK-O), and 5) E. acervulina-infected chickens fed a basal diet mixed with B. subtilis-cNK-2 at 1 × 1010 cfu/kg feed (CNK-F). The challenge consisted of 5,000 sporulated E. acervulina oocysts through oral gavage on d 15. Body weights were measured on d 7, 14, 21, and 23. Duodenal tissue and digesta samples were collected at 6 d postinfection (dpi) to assess the gut integrity, oxidative stress, mucosal immunity, and the gut microbiome. Fecal samples were collected from 6 to 8 dpi to enumerate the oocyst shedding. Chickens in the CNK-O group showed improved (P < 0.05) growth performance, gut integrity, and mucosal immunity compared to PC, comparable to chickens in the MO group. Chickens in the MO, CNK-F, and CNK-O treatment groups all showed lower (P < 0.05) oocyst shedding compared to PC chickens. Moreover, distinct cytokine profile, oxidative stress measures, tight junction proteins, and shifts in the gut microbiome with associated functional changes were observed in all challenge groups. In conclusion, we showed that the oral administration of B. subtilis-cNK-2 improved growth performance, enhanced local protective immunity, and reduced fecal oocyst shedding in broiler chickens infected with E. acervulina, demonstrating potential use of B. subtilis-cNK-2 as an alternative to antibiotics to protect chickens against coccidiosis.

Prostate-specific Antigen Nadir and Cancer-Control Outcomes in Real-world Apalutamide-treated Metastatic Hormone-Sensitive Prostate Cancer Patients: A Single-Center Analysis

Background and objectiveCurrently available post hoc phase 3 trial–derived data suggest better cancer-control outcomes in apalutamide-treated metastatic hormone-sensitive prostate cancer (mHSPC) patients achieving an (ultra)low prostate-specific antigen (PSA) nadir. This study aims to validate ultralow PSA nadir cutoffs. MethodsRelying on an institutional prostate cancer database, 107 eligible patients were yielded. The currently available PSA nadir cutoffs (SWOG trial: <0.2 ng/ml; ultralow TITAN trial: ≤0.02 vs 0.02–0.2 vs >0.2 ng/ml) and PSA responses (≥99%) were tested for time to castration-resistant prostate cancer (ttCRPC) and overall survival (OS) in mHSPC patients treated with apalutamide. Finally, comparisons were made against abiraterone mHSPC treatment. Key findings and limitationsOverall, 107 mHSPC patients treated with apalutamide at a median age of 68 yr and baseline PSA of 29 ng/ml were included. The highest proportion of included patients (40.2%) achieved an ultralow PSA nadir of ≤0.02 ng/ml. Patients reaching the SWOG 9346–defined PSA nadir of <0.2 ng/ml and ultralow PSA nadir of ≤0.02 ng/ml harbored the longest time to metastatic castration-resistant prostate cancer (mCRPC) and OS (all p < 0.05). Moreover, 80% of mHSPC patients treated with apalutamide achieved a PSA response of ≥99%. These patients also harbored better time to mCRPC and OS outcomes, relative to patients with a <99% PSA response (both p < 0.05). In the second step of analyses, a comparison against abiraterone patients showed a significantly higher rate of achieving an ultralow PSA nadir of ≤0.02 ng/ml: 40.2% versus 8.8% for apalutamide versus abiraterone, resulting in a significantly longer ttCRPC for the apalutamide-treated (37 mo) than for the abiraterone-treated (22 mo) group (p = 0.001), even after multivariable adjustment and in sensitivity analyses for high-risk mHSPC patients only. The study is limited by its retrospective design. Conclusions and clinical implicationsIn the real-world setting, most mHSPC patients treated with apalutamide achieve an ultralow PSA nadir, which is associated with better cancer-control outcomes. Moreover, a PSA response of ≥99% predicts better outcomes. In head-to-head comparisons, apalutamide achieves better PSA kinetics and ttCRPC outcomes than abiraterone. Patient summaryA prostate-specific antigen (PSA) nadir of <0.02 ng/ml and PSA responses ≥99% are associated with better cancer-control outcomes in metastatic hormone-sensitive prostate cancer patients treated with apalutamide.

Effect of herbal irrigants on surface roughness of intraradicular dentin using quantitative method of 3D surface texture analysis

Replacing the conventional endodontic irrigants with herbal agents could avoid complications associated with using sodium hypochlorite (NaOCl). Endodontic irrigants alter the surface roughness of the dentinal wall surface, which affects sealer mechanical retention. This study aimed to assess the effect of experimental herbal Moringa oleifera and orange peel extract irrigant on intraradicular dentin (IRD) surface roughness using quantitative 3D surface analysis by scanning electron microscopy (SEM) regarding the smear layer assessment. Sixty human root sections were divided into four groups (n = 15): NaOCl combined with 17% ethylenediaminetetraacetic acid (EDTA); negative control (saline); moringa extract (MO); and orange oil (OO). SEM images were assessed quantitatively for surface roughness (Ra) in the coronal, middle, and apical IRD. The data were analysed by Kruskal–Wallis, Friedman, and Dunn’s tests. All groups showed statistically significant differences (P = 0.007). MO exhibited significantly greater Ra values at the coronal, middle, and apical root levels than OO (P = 0.007, 0.009, and 0.046, respectively). There was no significant change in Ra values at various root levels within each group at P = 0.091, 0.819, 0.819, and 0.549 for the EDTA, saline, MO, and OO groups. Considerable (IRD) surface roughness analysis makes Moringa extract a promising herbal endodontic irrigant alternative to the NaOCl plus EDTA regimen.

P-510 The impact of the severe male factor in the egg donation cycles using preimplantation genetic test for aneuploidy

Abstract Study question Does severe male factor affect the euploidy rate and IVF outcomes in donor egg ICSI cycles using PGT-A? Summary answer Severe male factor affects the euploidy rate in egg donation cycles, however, no statistical differences were reported in live birth and cumulative live birth rate. What is known already Around 50% of couples seeking fertility treatment have male-factor infertility. Intracytoplasmic sperm injection (ICSI) relies on evaluating sperm morphology, but the direct relationship between semen quality and embryonic potential remains unclear. Evidence indicates that poor semen characteristics correlate with an increase in aneuploidy rate of spermatozoa. Therefore, pregenetic testing for aneuploidies (PGT-A) is recommended in cases of male factor infertility. The relationship between aneuploidy rates and abnormal sperm remains a debated topic. The use of the egg donation model offers a valuable chance to isolate the male-related factor and evaluate its influence on the occurrence of embryonic aneuploidies. Study design, size, duration This is a retrospective, observational, cohort study including all European IVI clinics. The study included egg donation cycles using pre-implantation genetic testing for aneuploidies (PGT-A) generated in IVI clinics from January 2017 until December 2023. 690 egg donation cycles were included in the study, N = 202 in the group with sperm &amp;lt; 5mil/ml, N = 102 in the sperm group with 5-15 mil/ml and N = 386 in the group with sperm &amp;gt;15 mil/ml. Participants/materials, setting, methods The study included women between 30-49 years undergoing egg-donor cycles, using fresh/frozen sperm Sperm samples were derived after 2-5 days of abstinence. The cycles of egg donation were divided into three groups according to sperm concentration, severe oligozoospermia (SO, &amp;lt; 5mil/ml), moderate oligozoospermia (MO, between 5-15 mil/ml), and control group(&amp;gt;15 mil/ml). Trophectoderm biopsy was performed on day 5 or 6 and subsequent analysis used the next sequencing generation (NGS). Single euploid blastocyst transfers were included. Main results and the role of chance The fertilization rate was decreased in SO (73.33 ± 16.19) than in the MO group (79.07 ±12.45) and control group (77.80 ±14.72) p = 0.0047. The number of blastocysts was higher in the control (5.80 ± 2.72) and MO (5.97± 2.78) than in the SO group (4.99 ± 2.40), p = &amp;lt;0.001. The number of euploid blastocysts was decreased in SO (3.21 ± 2.07) than in the control (4.09 ± 2.41) and MO group (4.05 ± 2.15), p = &amp;lt;0.001. The euploidy rate of SO decreased (63.32 ±26.39) compared to the control (69.67 ± 25.08) and MO group (68.55 ± 20.37), p = 0.012. The logistic regression model included possible confounders (male age, age donor, male BMI, sperm motility, sperm morphology and sperm concentration) that showed no effect on the euploidy rate. The pregnancy rate was similar across the groups 69.77% vs 66.05% vs 66.23%, p = 0.54. No statistical differences were reported for the clinical pregnancy rate 62.79% vs 61.73% vs 58.40%, p = 0.44, and the live birth rate 62.79% vs 61.73% vs 58.40%, p = 0.44. 48.05 vs 46.38% vs 42.64%, p = 0.37. No differences were reported in the miscarriage rate (p = 0.37) and CLBR (p = 0.26). Limitations, reasons for caution The retrospective nature of the study and the sample size represent the principal limitations of the study. The clinical reason for severe male factors was not considered in the study. Wider implications of the findings SO affects the quality affect the early embryonic potential through an increase in aneuploidy, despite no clinical effects.The use of PGT-A in case of severe male factor remains not justified in the egg donation.Future prospective multi-center studies are needed to highlight the effect of sperm quality on early embryonic potential. Trial registration number not applicable

OBTAINING HUMATE-, NITROGEN AND MOLYBDENUM-CONTAINING LIQUID ORGANOMINERAL FERTILIZERS

The presence of humic substances (HS) and microelements in liquid organomineral fertilizers (LOMF) makes it possible to balance the mineral nutrition of plants and thereby increase the agricultural crops yield. The use of such fertilizers significantly increases the efficiency and reduces the costs of using mineral fertilizers. The aim of this work is to study the patterns of new types LOMF obtaining process, including macro- and microelements and physiologically active humic substances, and its composition and properties. Methods. Chemical analysis, inductively coupled plasma atomic emission spectrometer, infrared spectroscopy. Results and discussion. The processes of synthesis of LOMF through the interaction of sodium humate and ammonium heptamolybdate tetrahydrate were studied. Analysis of obtained results showed the same nature of the composition dependence and properties of the obtained LOMF on time. It was found that increasing the time from 10 to 120 min leads to an increase in the yield of humic acids (HAdaf) to 40.08%, the N content to 4.62% and Mo to 0.17%, the amount of COOH to 1.80 mg-eq/g and OHphen. groups – up to 0.71 mg-eq/g. It has been shown that with an increase in S:L ratio from 0.3:100 to 0.7:100, the HAdaf decreases to 36.97%, and the N and Mo contents increase, respectively, to 6.0 and 0.37%. Conclusion. The regularities of the time influence and S:L ratios on the composition and properties of LOMF samples have been established. It has been shown that an increase in time and S:L ratio contributes to an increase in the content of N and Mo, the carboxyl and phenolic hydroxyl groups. The changes in these parameters have different effects on the HAdaf. The presence of HS, N, Mo, COOH and OHphen groups in the resulting products allows them to be used in agriculture and for restoring soil fertility.

Mutation profiles and outcomes of patients with acute myeloid leukemia with autoimmune disease.

6536 Background: Therapy-related acute myeloid leukemia (t-AML) defines a group of patients who develop AML after being treated with chemotherapy or radiation therapy. Most of these patients have a history of malignancy, but some have exposure to cytotoxic therapy for non-cancerous conditions such as autoimmune diseases (AD). This study looked at the characteristics, genetics, and outcomes of patients with AD and AML. Methods: This study included patients diagnosed with AML from 1999 - 2019. AML was divided into 4 groups: de novo AML, AD- AML (AML after AD diagnosis), t-AML (excluding AD-AML), secondary AML (s-AML) (AML arising out of myelodysplastic syndrome or myeloproliferative neoplasm). All molecular data were obtained via next generation sequencing (NGS) of genes frequently observed to be mutated in AML and analyzed using Chi-square test. BUM method was used to control false-discovery rate (FDR) at 8%. Overall survival (OS) and progression free survival (PFS) were estimated by Kaplan-Meier method and compared using log rank test. Results: A total of 1587 pts were included: 10.1% (n=160) with AD-AML, 71.3% (n=1131) de novo AML, 13.1% sAML (n=208) and 5.6% t-AML (n=88). The median age at diagnosis was 54.5 years; 54% were male; 67.3% received intensive induction therapy (Intensive defined as a 7+3 regimen). Cytogenetic (CG) data were available for 97.3% pts. According to MRC 2010 classification, CG were favorable in 14%, intermediate in 57%, and poor in 28% of the pts. The most prevalent AD were Crohn's/ulcerative colitis (n=30, 17%) and rheumatoid arthritis (n=23, 13%); 10.6% of pts had 2 disorders. In AD-AML group, the median age at diagnosis of first AD was 53 years; the median interval from AD diagnosis to AML was 82.5 months (mo); the majority of pts (56.25%) did not receive treatment (not including steroids) for their AD; 23.8% of pts were treated with immunomodulating agents, 23.1% with cytotoxic agents and 15% with anti-inflammatory agents; 20.1% received ≥ 2 drug classes. Poor risk CG were more common in AD-AML than in de novo AML (30% vs. 12.2%, p&lt;.0001). Mutations in NF1 were more common in AD-AML (9.7%) than in de novo (2.7%), sAML (1.0%), and t-AML (2.7%, p=0.024). FLT3 mutations were less common in AD-AML (9.5%) than in de novo (36.1%) and t-AML (33.3%, p=0.004). Mutations in SRSF2 were more common in AD-AML (20.3%) than in de novo (12.3%) and sAML (8.8%, p=0.119). Median PFS varied among de novo (8 mo), AD-AML (6 mo) and t-AML (5 mo) groups. For the AD-AML grp, the median OS was 9 months; less than the de novo AML (11 mo), and greater than t-AML (6 mo) and sAML (6 mo, p&lt;0.0001). Conclusions: Patients with AML and a prior history of AD have CG profile and outcomes similar to those with t-AML but with distinct molecular features (i.e. NF1 and SRSF2). These findings need to be validated in large series; however, they suggest that the MAPK signaling pathway as well as spliceosome inhibitors might be a future focus of investigation in pts with AD-AML.

Chronic cypermethrin induced toxicity and molecular fate assessment within common carp (Cyprinus carpio) using multiple biomarkers approach and its novel therapeutic detoxification

Cypermethrin (CYP) is a chemical of emerging concern which has persistent and bioaccumulating impacts as it can be found extensively in freshwater ecosystem and agricultural products. It has exposure risk and toxic effects over human edible fish, as common carp. Four groups were designed for toxicity assessment and detoxification approach: control group (CL), CYP exposure group (CYP), CYP + 10% M. oleifera leaves and 10% M. oleifera seeds (CMO group), 10% M. oleifera leaves and 10% M. oleifera seeds (MO group). Trial period was forty days during which cohort of 240 fish in CYP and CMO group was exposed to 1/5 of 96h LC50 of CYP (0.1612 μg/L). CYP-exposed carp exhibited lower growth parameters, but carp fed with 10% M. oleifera seeds and leaves showed significant improvement in growth rate (SGR, RGR) and weight gain (WG) as compared to the control group. CYP exposure negatively affected haemato-biochemical parameters. Moreover, CYP exposure also led to oxidative stress, damaged immunological parameters, genotoxicity and histopathological damage in liver and intestinal cells. Whereas, M. oleifera supplementation has ameliorated these conditions. Thereby, supplementation with M. oleifera is potential and novel therapeutic detoxication approach for common carp and human health against persistent and bioaccumulating emerging chemicals.

Monolithic hybrid abutment crowns: Influence of crown height, crown morphology and material on the implant-abutment complex.

This in vitro study investigated the influence of material selection, crown morphology, and vertical crown height on the biomechanical behavior of monolithic hybrid abutment crowns (HACs). Ninety implants were embedded in accordance with ISO standard 14801; ninety HACs were mounted (N=90). Monolithic crowns with varying group-specific designs were luted using titanium bases. HACs were fabricated from monolithic lithium disilicate ceramic (LD) or zirconia-reinforced lithium silicate ceramic (ZLS). The crown morphology was either maxillary premolar (LD_PM, ZLS_PM) or molar (LD_MO). The three groups were further divided into three subgroups of ten specimens, each designed with a small (7.5 mm), middle (10.5 mm), and high (13.5 mm) configuration of crown heights (N=10). A load-to-failure test at 30° off-axis was conducted using a universal testing machine until failure. For statistical analysis, Kolmogorov-Smirnov and Mann-Whitney U tests were conducted (P < 0.05). All LD_MO groups presented the highest failure values (808.7 to 947.9 N), followed by the LD_PM (525.8 to 722.8 N) and ZLS_PM groups (312.6 to 478.8N). A comparison between LD and ZLS materials (P < 0.001) as well as the crown morphology (P < 0.001) showed significant differences in failure values. The values in the subgroups of ZLS_PM (low, middle, high) decreased as the crown height increased. The fracture modes showed no consistent patterns across the test groups. Material selection, crown morphology, and vertical crown height appear to be important factors that may influence the clinical failure values and patterns of HACs.

The Impact of Delayed Radical Prostatectomy on Recurrence Outcomes After Initial Active Surveillance: Results from a Large Institutional Cohort

Background and objectiveActive surveillance (AS) of prostate cancer (PCa) involves regular monitoring for disease progression. The aim is to avoid unnecessary treatment while ensuring appropriate and timely treatment for those whose disease progresses. AS has emerged as the standard of care for low-grade (Gleason grade 1, GG 1) PCa. Opponents are concerned that initial undersampling and delay of definitive management for patients with GG 2 disease may lead to adverse outcomes. We sought to determine whether the timing for definitive management of GG 2 PCa, either upfront or after initial AS, affects recurrence outcomes after radical prostatectomy (RP). MethodsParticipants were diagnosed with cT1–2N0/xM0/x, prostate-specific antigen (PSA) <20 ng/ml, and GG 1–2 PCa between 2000 and 2020 and underwent immediate RP for GG 2 or AS followed by delayed RP on upgrading to GG 2. The outcome was recurrence-free survival (RFS) after surgery, with recurrence defined as either biochemical failure (2 PSA measurements ≥0.2 ng/ml) or a second treatment. Multivariable Cox proportional-hazards regression models were used to calculate associations between the timing for definitive RP and the risk of recurrence, adjusted for age at diagnosis, percentage of positive biopsy cores (PPC), PSA density, PSA before RP, year of diagnosis, surgical margins, genomic risk score, and prostate MRI findings. Key findingsOf the 1259 men who met the inclusion criteria, 979 underwent immediate RP after diagnosis of GG 2, 190 underwent RP within 12 mo of upgrading to GG 2 on AS, and 90 men underwent RP >12 mo after upgrading to GG 2. The 5-yr RFS rates were 81% for the immediate RP group, 80% for the delayed RP ≤12 mo, and 70% for the delayed RP >12 mo group (univariate log-rank p = 0.03). Cox multivariable regression demonstrated no difference in RFS outcomes between immediate RP for GG 2 disease and delayed RP after upgrading on AS. PPC (hazard ratio [HR] per 10% increment 1.08, 95% confidence interval [CI] 1.02–1.15; p = 0.01) and PSA before RP (HR 1.06, 95% CI 1.03–1.09; p < 0.01) were significantly associated with the risk of recurrence. Conclusions and clinical implicationsPPC and PSA before RP, but not the timing of definitive surgery after upgrade to GG 2, were associated with the risk of PCa recurrence after RP on multivariable analysis. These findings support the safety of AS and delayed definitive therapy for a subset of patients with GG 2 disease. Patient summaryIn a large group of 1259 patients with low-grade prostate cancer, we found that delaying surgical treatment after an initial period of active surveillance resulted in no differences in prostate cancer recurrence. Our results support the safety of active surveillance for low-grade prostate cancer.

Reduction in retinal microvascular perfusion during migraine attacks.

To determine if there are changes in structure and function of the retinal vasculature during and between migraine attacks using optical coherence tomography angiography (OCTA). Migraine attacks commonly include visual symptoms, but the potential role of the retina in these symptoms is not well understood. OCTA is a rapid, non-invasive imaging technique that is used to visualize the retinal microvasculature with high spatial resolution in a clinical setting. In this study we used OCTA to quantify different features of the retinal vasculature in patients with migraine during and between attacks, as well as in healthy controls (HCs). We performed a prospective cohort study of 37 patients with migraine with aura (MA) (median [interquartile range, IQR] age of 37 [14] years, 86% female) and 30with migraine without aura (MO) (median [IQR] age of 37 [17] years, 77% female) and 20 HCs (median [IQR] age of 35 [7] years, 50% female). Macular OCTA scans were obtained for all participants for the interictal analysis. In 12 MA and eight MO, scans were captured both during and outside of migraine attacks and five HCs had initial and repeat scans. In addition to analyzing the morphology of the foveal avascular zone, we calculated the vessel flux index (VFI), which is an indicator of retinal perfusion and conventional metrics (such as vessel area density) in the foveal and parafoveal regions. There was a significant difference in the parafoveal VFI in the ictal state between the groups (p = 0.009). During migraine attacks there was a significant reduction in the parafoveal region VFI in MA (-7%, 95% confidence interval [CI] -10% to -4%; p = 0.006) and MO (-7%, 95% CI -10% to -3%; p = 0.016) from their interictal baseline as compared to the change between repeat scans in HCs (2%, 95% CI -3% to 7%). Interictally, there was a mean (standard deviation [SD]) 13% (10%) (p = 0.003) lower blood perfusion in the MA group as compared to the MO group in the foveal region (mean [SD] 0.093 [0.023] vs. 0.107 [0.021], p = 0.003). Interictal analysis also revealed higher circularity in the superficial foveal avascular zone in the MA group compared with the MO group (mean [SD] 0.686 [0.088] vs. 0.629 [0.120], p = 0.004). In addition, interictal analysis of the patients with MA or MO and unilateral headache showed increased retinal vascular parameters consistent with greater perfusion in the eye ipsilateral to the side of the pain as compared with the contralateral eye. These results indicate that perfusion is reduced in MA and MO in the parafoveal retina during the ictal period. Interictally, the foveal retina in MA has reduced perfusion when compared to the foveal retina in MO. Patients with unilateral headache showed interictal asymmetry of retinal perfusion between eyes. These results indicate that changes in retinal perfusion could be a part of migraine pathophysiology, and that distinct retinal vascular signatures identified with OCTA could represent biomarkers for migraine.

Molybdenum and cadmium cause blood–testis barrier dysfunction through ROS-mediated NLRP3 inflammasome activation in sheep

In this study, 24 healthy male sheep were divided into four groups: the control group, Mo group (45 mg Mo·kg-1·BW), Cd group (1 mg Cd·kg-1·BW), and Mo + Cd group (45 mg Mo·kg-1·BW + 1 mg Cd·kg-1·BW). The experiment was last for 50 d. The results showed that Mo and Cd co-exposure induced histopathological changes and ultrastructural damage, decreased the mRNA and protein expression levels of BTB (blood-testis barrier)-related factors (CX-43, ZO-1, OCLN) (P < 0.05) and the T-SOD and CAT activity (P < 0.05), increased the MDA content (P < 0.05) and the proinflammatory factors levels (P < 0.05) in sheep testes. Moreover, the results showed that a sharp decline in BTB-related factors and antioxidase activity, and a significant increase in reactive oxygen species (ROS) levels (P < 0.05) and the expression levels of NLRP3 inflammasome-related factors (P < 0.05) in primary Sertoli cells (SCs) under Mo and Cd co-exposure. However, treatment with a ROS scavenger or NLRP3 inflammasome inhibitors could relieve BTB damage and oxidative injury, reduce the production of ROS (P < 0.05) and decrease the level of inflammatory factors (P < 0.05). Overall, these results indicated that Mo and Cd co-exposure reduced BTB-related protein levels and promoted ROS production and inflammatory reactions by activating the ROS/NLRP3 inflammasome pathway in sheep testes, which eventually induced reproductive toxicity.

Co-exposure to molybdenum and cadmium evokes necroptosis and decreases apoptosis in duck myocardium

Superfluous molybdenum (Mo) and cadmium (Cd) in the environment are detrimental to organisms through their accumulation. The NF-κB/TNF-α axis plays a vital part in regulating necroptosis and apoptosis. However, the impacts of Mo and/or Cd on myocardium injury in ducks and the function of NF-κB/TNF-α axis are not clear in the process. In this research, ducks exposed to different dosages of Mo and/or Cd were applied as the study object. The findings substantiated that the accumulation of Mo and/or Cd caused elements imbalance and necroptosis in myocardial tissue. As p-NF-κB/TNF-α expression up-regulated, RIPK1/RIPK3/p-MLKL expression significantly increased in all treatment groups, while the expression of c-caspase-8/3 markedly decreased. Moreover, apoptosis rate obviously decreased in Cd treated groups and clearly elevated in Mo group. Mitochondria-mediated apoptosis was activated by excessive Mo and inhibited by Mo + Cd, but Cd exposure alone had little effect on it. Collectively, our research confirmed that Mo and/or Cd evoked necroptosis via NF-κB/TNF-α axis, and decreased death receptor-mediated apoptosis in duck myocardium, the impacts of Mo and/or Cd on mitochondrial-mediated apoptosis were different. These results are significant for studying toxicology of Mo and/or Cd and preserving the ecosystem.

Effects of Pera Orange Juice and Moro Orange Juice in Healthy Rats: A Metabolomic Approach.

Sixty male Wistar rats were allocated into 3 groups: control (C), Pera orange juice (PO), and Moro orange juice (MO). PO and MO groups received Pera orange juice or Moro orange juice, respectively, and C received water with maltodextrin (100 g/L). Echocardiogram and euthanasia were performed after 4 weeks. Plasma metabolomic analysis was performed by high-resolution mass spectrometry. Type I collagen was evaluated in picrosirius red-stained slides and matrix metalloproteinase (MMP)-2 activity by zymography. MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2, TIMP-4, type I collagen, and TNF-α protein expression were evaluated by Western blotting. We differentially identified three metabolites in PO (N-docosahexaenoyl-phenylalanine, diglyceride, and phosphatidylethanolamine) and six in MO (N-formylmaleamic acid, N2-acetyl-L-ornithine, casegravol isovalerate, abscisic alcohol 11-glucoside, cyclic phosphatidic acid, and torvoside C), compared to controls, which are recognized for their possible roles in cardiac remodeling, such as extracellular matrix regulation, inflammation, oxidative stress, and membrane integrity. Cardiac function, collagen level, MMP-2 activity, and MMP-9, TIMP-2, TIMP-4, type I collagen, and TNF-α protein expression did not differ between groups. Ingestion of Pera and Moro orange juice induces changes in plasma metabolites related to the regulation of extracellular matrix, inflammation, oxidative stress, and membrane integrity in healthy rats. Moro orange juice induces a larger number of differentially expressed metabolites than Pera orange juice. Alterations in plasma metabolomics induced by both orange juice are not associated with modifications in cardiac extracellular matrix components. Our results allow us to postulate that orange juice may have beneficial effects on pathological cardiac remodeling.

Role of Caveolin-1 on the molybdenum and cadmium exposure induces pulmonary ferroptosis and fibrosis in the sheep

Molybdenum (Mo) is an essential trace element that exists in all tissues of the human body, but excessive Mo intake has a toxic effect. Cadmium (Cd) is a widely known and harmful heavy metal that exists in the environment. Although studies on Mo and Cd are available, it is still unknown how the combination of Mo and Cd causes pulmonary injury. Forty-eight sheep that were 2 months old were chosen and randomly separated into four groups as follows: Control group, Mo group, Cd group, and Mo + Cd group. The experiment lasted 50 days. The results showed that Mo and/or Cd caused significant pathological damage and oxidative stress in the lungs of sheep. Moreover, Mo and/or Cd exposure could downregulate the expression levels of xCT (SLC7A11 and SLC3A2), GPX4 and FTH-1 and upregulate the expression levels of PTGS2 and NCOA4, which led to iron overload and ferroptosis. Ferroptosis induced Wnt/β-catenin-mediated fibrosis by elevating the expression levels of Caveolin-1 (CAV-1), Wnt 1, Wnt3a, β-catenin (CTNNB1), TCF4, Cyclin D1, mmp7, α-SMA (ACTA2), Collagen 1 (COL1A1) and Vimentin. These changes were particularly noticeable in the Mo and Cd combination group. In conclusion, these data demonstrated that Mo and/or Cd exposure led to lung ferroptosis by inhibiting the SLC7A11/GSH/GPX4 axis, which in turn increases CAV-1 expression and subsequently activates the Wnt/β-catenin pathway, leading to fibrosis in sheep lungs.

Molybdenum and cadmium co-induce necroptosis through Th1/Th2 imbalance-mediated endoplasmic reticulum stress in duck ovaries

Cadmium (Cd) and excess molybdenum (Mo) pose serious threats to animal health. Our previous study has determined that Cd and/or Mo exposure can cause ovarian damage of ducks, while the specific mechanism is still obscure. To further investigate the toxic mechanism of Cd and Mo co-exposure in the ovary, forty 8-day-old female ducks were randomly allocated into four groups for 16 weeks, and the doses of Cd and Mo in basic diet per kg were as follows: control group, Mo group (100 mg Mo), Cd group (4 mg Cd), and Mo + Cd group (100 mg Mo + 4 mg Cd). Cadmium sulfate 8/3-hydrate (CdSO4·8/3H2O) and hexaammonium molybdate ((NH4)6Mo7O24·4H2O) were the origins of Cd and Mo, respectively. At the 16th week of the experiment, all ovary tissues were collected for the detection of related indexes. The data indicated that Mo and/or Cd induced trace element disorders and Th1/Th2 balance to divert toward Th1 in the ovary, which activated endoplasmic reticulum (ER) stress and then provoked necroptosis through triggering RIPK1/RIPK3/MLKL signaling pathway, and eventually caused ovarian pathological injuries and necroptosis characteristics. The alterations of above indicators were most apparent in the joint group. Above all, this research illustrates that Mo and/or Cd exposure can initiate necroptosis through Th1/Th2 imbalance-modulated ER stress in duck ovaries, and Mo and Cd combined exposure aggravates ovarian injuries. This research explores the molecular mechanism of necroptosis caused by Mo and/or Cd, which reveals that ER stress attenuation may be a therapeutic target to alleviate necroptosis.

Molybdenum and/or cadmium induce NLRP3 inflammasome production by causing mitochondria-associated endoplasmic reticulum membrane dysfunction in sheep hepatocytes

Accumulation of the heavy metals molybdenum (Mo) and cadmium (Cd) in the liver can induce organelle damage and inflammation, resulting in hepatotoxicity. The effect of Mo and/or Cd on sheep hepatocytes was investigated by determining the relationship between the mitochondria-associated endoplasmic reticulum membrane (MAM) and NLRP3 inflammasome. Sheep hepatocytes were divided into four groups: the control group, Mo group (600 μM Mo), Cd group (4 μM Cd) and Mo + Cd group (600 μM Mo+4 μM Cd). The results showed that Mo and/or Cd exposure increased the levels of lactate dehydrogenase (LDH) and nitric oxide (NO) in the cell culture supernatant, elevated the levels of intracellular Ca2+ and mitochondrial Ca2+, downregulated the expression of MAM-related factors (IP3R, GRP75, VDAC1, PERK, ERO1-α, Mfn1, Mfn2, ERP44), shortened the length of the MAM and reduced the formation of the MAM structure, eventually causing MAM dysfunction. Moreover, the expression levels of NLRP3 inflammasome-related factors (NLRP3, Caspase1, IL-1β, IL-6, TNF-α) were also dramatically increased after Mo and Cd exposure, triggering NLRP3 inflammasome production. However, an IP3R inhibitor, 2-APB treatment significantly alleviated these changes. Overall, the data indicate that Mo and Cd coexposure leads to structural disruption and dysfunction of MAM, disrupts cellular Ca2+ homeostasis, and increases NLRP3 inflammasome production in sheep hepatocytes. However, the inhibition of IP3R alleviates NLRP3 inflammasome production induced by Mo and Cd.