Puberty Blocker and Aging Impact on Testicular Cell States and Function.

Spermatogonial stem cell (SSC) acquisition of meiotogenetic state during puberty to produce genetically diverse gametes is blocked by drugs collectively referred as 'puberty blocker' (PB). Investigating the impact of PB on juvenile SSC state and function is challenging due to limited tissue access and clinical data. Herein, we report largest clinically annotated juvenile testicular biorepository with all children with gender dysphoria on chronic PB treatment highlighting shift in pediatric patient demography in US. At the tissue level, we report mild-to-severe sex gland atrophy in PB treated children. We developed most extensive integrated single-cell RNA dataset to date (>100K single cells; 25 patients), merging both public and novel (52 month PB-treated) datasets, alongside innovative computational approach tailed for germ cells and evaluated the impact of PB and aging on SSC. We report novel constitutional ranges for each testicular cell type across the entire age spectrum, distinct effects of treatments on prepubertal vs adult SSC, presence of spermatogenic epithelial cells exhibiting post-meiotic-state, irrespective of age, puberty status, or PB treatment. Further, we defined distinct effects of PB and aging on testicular cell lineage composition, and SSC meiotogenetic state and function. Using single cell data from prepubertal and young adult, we were able to accurately predict sexual maturity based both on overall cell type proportions, as well as on gene expression patterns within each major cell type. Applying these models to a PB-treated patient that they appeared pre-pubertal across the entire tissue. This combined with the noted gland atrophy and abnormalities from the histology data raise a potential concern regarding the complete 'reversibility' and reproductive fitness of SSC. The biorepository, data, and research approach presented in this study provide unique opportunity to explore the impact of PB on testicular reproductive health.

A facile N-doped NiFe(B) (Oxy)hydroxide monolithic electrode for enhanced water oxidation.

N-doped NiFe(B) (oxy)hydroxide can promote the catalytic activity for an alkaline oxygen evolution reaction (OER) significantly, but fabrication is difficult. Herein, we introduced a B-induction route to the N-NiFe(B) (oxy)hydroxide monolithic electrode under a relatively low temperature. We observed an excellent catalytic performance benefiting from an optimal electronic structure, enlarged surface area and improved hydrophilicity. Moreover, this mild protocol could be extended to fabricate an S-doped NiFe-based catalyst. This research could aid large-scale manufacture.

Radical-Mediated Decarboxylative C-C and C-S Couplings of Carboxylic Acids via Iron Photocatalysis.

Despite the significant success of decarboxylative radical reactions, the catalytic systems vary considerably upon different radical acceptors, requiring renewed case-by-case reaction optimization. Herein, we developed an iron catalytic condition that enables the highly efficient decarboxylation of various carboxylic acids for a range of radical transformations. This operationally simple protocol was amenable to a wide array of radical acceptors, delivering structurally diverse oxime ethers, alkenylation, alkynylation, thiolation, and amidation products in useful to excellent yields (>40 examples, up to 95% yield).

The characteristics of H6 against Microcystis aeruginosa.

Algal bloom caused by Microcystis aeruginosa has always been the focus of attention; microbial algal control has the advantages of significant effect, low investment cost, and environmental friendliness; the use of microbial technology to inhibit the bloom has a broad prospect for development. In this study, a strain of Enterobacterium algicidal bacteria screened from a river was used to study the algicidal characteristics against Microcystis aeruginosa using SEM, 3-D EEM and zeta potential. The results showed that the optimal dosage (v/v) of the strain was 5% and the removal rate of algal cells was 70% after 7 days. When the algal density was OD680nm = 0.3, the removal rate of algal cells reached 83% after 7 days. In the pH range of 5 ~ 11, the removal rate of algal cells was 70 ~ 80% after 7 days. Algicidal bacteria H6 is mainly indirect algae lysis and is supplemented by direct algae lysis. Algicidal bacteria H6 removes algicidal substances by secreting high temperature resistant algicidal substances and algicidal products are humic acids. Algicidal bacterium H6 was a strain of Enterobacterium with good algicidal effect in a wide pH range, which enriched the bacterial resources in the control of cyanobacteria bloom in water. The high temperature resistance of the algae-soluble substance secreted by the algae-soluble substance provided convenience for the subsequent preparation and application of bacterial powder.

Optimal Embryo Selection: The Irreplaceable Role of the Embryologist in an Age of Advancing Technology.

Background: Time-lapse incubators allow for ongoing evaluation of embryos without culture condition disruption. The use of time-lapse incubation has been shown to improve outcomes either by improving overall conditions or providing additional information to aid in embryo selection for transfer. Time-lapse incubators can also utilise morphokinetic models to rank embryos based on morphokinetic parameters. We sought to compare a morphokinetic model for embryo comparison to traditional morphologic evaluation. Aims: The aim of the study is to compare a morphokinetic model for embryo comparison to traditional morphologic evaluation. Settings and Design: This is a retrospective cohort design. Materials and Methods: Embryos cultured in a time-lapse culture system that had traditional morphologic evaluation, morphokinetic modelling and known live birth outcomes were included in this study. Embryos with unknown competence were excluded, including when two embryos were transferred with a single live birth resulted. Statistical Analysis Used: Receiver operating characteristic (ROC) curves were determined for both the morphologic analysis and the morphokinetic model on culture day 3 and day 5. Using the ROC-determined cutoff that optimised both sensitivity and specificity, a binary outcome for each test was analysed using agreement statistics to determine if one method of embryo evaluation was superior to the other. Results: Morphological and morphokinetic grading were both predictive of embryo competence on days 3 and 5. However, on day 3, morphologic grading was superior to morphokinetic grading with area under the curve (AUC) of 0.66 (P < 0.001) and 0.58 (P = 0.009), respectively. Contrarily, on day 5, the morphokinetic model had a higher AUC of 0.65 (P = 0.03) compared to the morphologic grading, AUC 0.56 (P = 0.02). Conclusion: Traditional morphology was noted to be a better diagnostic tool (higher AUC) on culture day 3 while a morphokinetic model was superior on day 5.

Quality control of Platycodon grandiflorum (Jacq.) A. DC. based on value chains and food chain analysis.

Platycodon grandiflorum (Jacq.) A. DC. has been proposed as a medicine and food homology, thus playing an important role in disease prevention and health promotion, with great potential for research and value in clinical application. We aimed to analyze stakeholders' production behavior and financial performance from a value chain (VC) perspective and provide a basis for improving the quality of P. grandiflorum and the interests of stakeholders. P. grandiflorum collected from different producing areas were chemically analyzed, and the quality of platycodin D was evaluated. Rstudio3.6.0 was used to analyze the correlation between total platycodins (as platycodin D, platycoside E, and platycodin D3) and platycodin D in P. grandiflorum, providing the basis for quality control of P. grandiflorum. In addition, we studied the anti-inflammatory and anti-cancer activities of P. grandiflorum extract under different links. Based on the food chain energy pyramid, the transfer efficiency of active components of P. grandiflorum in different links was studied. Accordingly, 10 different types of VCs were determined in producing P. grandiflorum. Our results show that vertical coordination has led to a more consistent traceability system and strict regulation of supply chains.

Radical Phosphorylation of Aliphatic C-H Bonds via Iron Photocatalysis.

The synthesis of tertiary phosphines(III) has been a long-standing challenge in synthetic chemistry because of inevitable issues including harsh conditions, sensitive organometallic reagents, and prefunctionalized substrates in traditional synthesis. Herein, we report a strategically novel C(sp3)-H bond phosphorylation that enables the assembly of structurally diverse tertiary phosphines(III) from industrial phosphine(III) sources under mild photocatalytic conditions. The merger of ligand-to-metal charge transfer (LMCT) of FeCl3 with the hydrogen atom-transfer (HAT) process is the key for the generation of alkyl radicals from hydrocarbons. Strikingly, this catalytic system can be successfully applied for the polymerization of electron-deficient alkenes.

The characteristics of nano-micron calcite particles/common bacteria complex and its interfacial interaction.

Based on the composite pollution of atmospheric microbial aerosol, this paper selects the calcite/bacteria complex as the research object which was prepared by calcite particles and two common strains of bacteria (Escherichia coli, Staphylococcus aureus) in the solution system. The morphology, particle size, surface potential, and surface groups of the complex were explored by modern analysis and testing methods, with an emphasis on the interfacial interaction between calcite and bacteria. The SEM, TEM, and CLSM results showed that the morphology of the complex could be divided into three types: bacteria adhering to the surface or edge of micro-CaCO3, bacteria aggregating with nano-CaCO3, and single nano-CaCO3 wrapping bacteria. The complex's particle size was about 2.07 ~ 192.4 times larger than the original mineral particles, and the nano-CaCO3/bacteria complex's particle size variation was caused by the fact that nano-CaCO3 has agglomeration in solution. The surface potential of the micro-CaCO3/bacteria complex (isoelectric point pH = 3.0) lies between micro-CaCO3 and bacteria, while the surface potential of the nano-CaCO3/bacteria complex (isoelectric point pH = 2.0) approaches the nano-CaCO3. The complex's surface groups were based primarily on the infrared characteristics of calcite particles, accompanied by the infrared characteristics of bacteria, displaying the interfacial interaction from the protein, polysaccharides, and phosphodiester groups of bacteria. The interfacial action of the micro-CaCO3/bacteria complex is mainly driven by electrostatic attraction and hydrogen bonding force, while the nano-CaCO3/bacteria complex is guided by surface complexation and hydrogen bonding force. The increase in the ß-fold/α-helix ratio of the calcite/S. aureus complex indicated that the secondary structure of bacterial surface proteins was more stable and the hydrogen bond effect was strong than the calcite/E. coli complex. The findings are expected to provide basic data for the mechanism research of atmospheric composite particles closer to the real environment.

Haploid Parthenogenetic Embryos Exhibit Unique Stress Response to pH, Osmotic and Oxidative Stress.

Preimplantation-stage embryos are susceptible to various types of stress when cultured in vitro. Parthenogenetic embryos that lack spermatozoa contribution exhibit aberrant developmental dynamics due to their uniparental origin. Herein, we assessed whether the absence of paternal genome affects the susceptibility of the embryos to pH, osmotic and oxidative stress. Haploid parthenogenetic embryos (HPE) (activated oocytes with 1 pronucleus and 2 polar bodies) were generated by incubating cumulus oocyte complexes of Swiss albino mice with 10 mM strontium chloride for 3 h. Normally fertilized embryos (NFE) (fertilized oocytes with 2 pronuclei and 2 polar bodies) were derived using in vitro fertilization. At 2-cell stage, both HPE and NFE were exposed to various stressors including pH (6.8 to 8.2), osmotic (isotonic, hypotonic, and hypertonic), and peroxidatic oxidative (H2O2, 25 µM) stress. Endoplasmic reticulum stress response, mitochondrial membrane potential, and the rate of blastocyst development were assessed. HPE were susceptible to alteration in the pH that was well tolerated by NFE. Similarly, HPE displayed remarkable difference in sensitivity to hypertonic stress and oxidative stress compared to NFE. The results clearly indicate that the oocytes that develop into embryos in the absence of paternal contribution are more vulnerable to environmental stressors, further highlighting the importance of spermatozoa contribution and/or the ploidy status in mitigating these stressors and towards healthy early embryo development.

Vitrification versus slow freezing of human ovarian tissue: a systematic review and meta-analysis of histological outcomes.

A systematic review and meta-analysis of pertinent literature published from 2006 to January 2022 were conducted to study and compare vitrification and slow freezing, the two prominent methods of ovarian tissue cryopreservation. The primary outcome measures for this study were (1) proportion of intact primordial follicles, (2) proportion of intact stromal cells, (3) proportion of DNA fragmentation in primordial follicles, and (4) mean primordial follicle density. This meta-analysis of 19 studies revealed a significantly greater proportion of intact stromal cells in vitrified tissue versus slow-frozen tissue. No significant differences upon pooled analyses were observed between the two cryopreservation methods with respect to the proportion of intact primordial follicles, proportion of DNA fragmentation, or mean primordial follicle density. Due to differences seen in stromal cell viability, vitrification may be a preferred option to preserve histology of tissue. However, more work should be done to compare the two freezing techniques with less heterogeneity caused by patients, samples, and protocols.

Embryo Blastomere Exclusion Identified in a Time-Lapse Culture System Is Associated with Embryo Ploidy.

This study examined blastomere exclusion which is seen during embryo development and could represent imperfect cell division or a mechanism of aneuploidy correction. This was a retrospective cohort study which included embryos cultured in a time-lapse incubator undergoing preimplantation genetic testing for aneuploidy (PGT-A) with trophectoderm biopsy. Embryos were evaluated for blastomere exclusion early in development, late in development, both, or neither. Blastomere exclusion was compared to embryo ploidy. Embryos with no blastomere exclusion had an aneuploidy rate of 52.9%, while embryos displaying blastomere exclusion at any stage had an aneuploidy rate of 68.5% (p < .001). Early blastomere exclusion was not significantly associated with an increased aneuploidy risk (59.2% vs. 52.9% in no blastomere exclusions; p = 0.22). However, embryos with late blastomere exclusion were significantly more likely to be aneuploid, compared to embryos with no blastomere exclusions (77.5% vs. 52.9%; p < 0.001) as were embryos with both early + late blastomere exclusions (71.2% vs. 52.9%; p < 0.001). Upon restricting the analysis to aneuploid embryos, the presence of any blastomere exclusion was not significantly associated with complex aneuploidy, defined as 2 more affected chromosomes (43.9% vs. 38.7%; p = 0.28). However, the proportion with adverse embryo genetics significantly increased with the timing of blastomere exclusion (38.7%, 37%, 45.5%, and 50% for none, early, late, and early + late; p = 0.043). Late blastomere exclusion or a combination of both early + late blastomere exclusion was associated with an increased risk of aneuploid embryo genetics. Embryo selection using time-lapse culture systems should incorporate these findings when untested embryos are transferred.

Outdoor Atmospheric Micro-/Nanomineral-Mediated Organochlorine Pesticides in Sichuan Basin, China: Adsorption, Occurrence, and Risk Assessment.

Atmospheric micro-/nanominerals play an important role in the adsorption, enrichment, and migration of organochlorine pesticides (OCPs). In the present study, the correlations between OCPs and minerals in outdoor atmospheric dustfall were investigated, and the correlations were used to speculate the source of p,p'-(dicofol+dichlorobenzophenone [DBP]), which is the sum of p,p'-dicofol and p,p'-DBP. Atmospheric dustfall samples were collected from 53 sites in the Chengdu-Deyang-Mianyang economic region in the Sichuan basin. In this region, 24 OCPs were analyzed by gas chromatography-tandem mass spectrometry. The average concentration of 24 OCPs was 51.2 ± 27.4 ng/g. The results showed that the concentration of Σ24 OCPs in urban areas was higher than that in suburban areas (p < 0.05). Minerals in atmospheric dustfall were semiquantitatively analyzed by X-ray diffraction. The primary minerals were quartz, calcite, and gypsum. A Spearman correlation analysis of OCPs and minerals showed that low-volatility OCPs could be adsorbed by minerals in atmospheric dustfall. A density functional theory simulation verified that p,p'-(dicofol+DBP) in atmospheric dustfall was primarily derived from the p,p'-dicofol adsorbed by gypsum. Isomeric ratio results suggested that the samples had weathered lindane and chlordane profiles and confirmed that residents in the Sichuan basin used technical dichlorodiphenyltrichloroethane. Finally, the OCPs were evaluated to determine the potential risk of cancer in adults and children from OCP exposure. Exposure to OCPs via atmospheric dustfall was safe for adults. The cancer risk for children exposed to OCPs was slightly lower than the threshold value (10-6 ) under a high dust ingestion rate, which poses a concern. Environ Toxicol Chem 2023;42:594-604. © 2022 SETAC.

The human embryonic genome is karyotypically complex, with chromosomally abnormal cells preferentially located away from the developing fetus.

STUDY QUESTION: Are chromosome abnormalities detected at Day 3 post-fertilization predominantly retained in structures of the blastocyst other than the inner cell mass (ICM), where chromosomally normal cells are preferentially retained? SUMMARY ANSWER: In human embryos, aneuploid cells are sequestered away from the ICM, partly to the trophectoderm (TE) but more significantly to the blastocoel fluid within the blastocoel cavity (Bc) and to peripheral cells (PCs) surrounding the blastocyst during Day 3 to Day 5 progression. WHAT IS KNOWN ALREADY: A commonly held dogma in all diploid eukaryotes is that two gametes, each with 'n' chromosomes (23 in humans), fuse to form a '2n' zygote (46 in humans); a state that remains in perpetuity for all somatic cell divisions. Human embryos, however, display high levels of chromosomal aneuploidy in early stages that reportedly declines from Day 3 (cleavage stage) to Day 5 (blastocyst) post-fertilization. While this observation may be partly because of aneuploid embryonic arrest before blastulation, it could also be due to embryo 'normalization' to a euploid state during blastulation. If and how this normalization occurs requires further investigation. STUDY DESIGN, SIZE, DURATION: A total of 964 cleavage-stage (Day 3) embryos underwent single-cell biopsy and diagnosis for chromosome constitution. All were maintained in culture, assessing blastulation rate, both for those assessed euploid and aneuploid. Pregnancy rate was assessed for those determined euploid, blastulated and subsequently transferred. For those determined aneuploid and blastulated (174 embryos), ICM (all 174 embryos), TE (all 174), Bc (47 embryos) and PC (38 embryos) were analyzed for chromosome constitution. Specifically, concordance with the original Day 3 diagnosis and determination if any 'normalized' to euploid karyotypes within all four structures was assessed. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients (144 couples) were undergoing routine preimplantation genetic testing for aneuploidy in three IVF clinical settings. Cleavage-stage biopsy preceded chromosome analysis by next-generation sequencing. All patients provided informed consent. Additional molecular testing was carried out on blastocyst embryos and was analyzed for up to four embryonic structures (ICM, TE, Bc and PC). MAIN RESULTS AND THE ROLE OF CHANCE: Of 463/964 embryos (48%) diagnosed as euploid at Day 3, 70% blastulated (leading to a 59% pregnancy rate) and 30% degenerated. Conversely, of the 501 (52%) diagnosed as aneuploid, 65% degenerated and 35% (174) blastulated, a highly significant difference (P < 0.0001). Of the 174 that blastulated, the ratio of '(semi)concordant-aneuploid' versus 'normalized-euploid' versus 'other-aneuploid' embryos was, respectively, 39%/57%/3% in the ICM; 49%/48%/3% in the TE; 78%/21%/0% in the PC; and 83%/10%/5% in the Bc. The TE karyotype therefore has a positive predictive value of 86.7% in determining that of the ICM, albeit with marginally higher aneuploid rates of abnormalities (P = .071). Levels of abnormality in Bc/PC were significantly higher (P < 0.0001) versus the ploidy of the ICM and TE and nearly all chromosome abnormalities were (at least partially) concordant with Day 3 diagnoses. LIMITATIONS, REASONS FOR CAUTION: The results only pertain to human IVF embryos so extrapolation to the in vivo situation and to other species is not certain. We acknowledge (rather than lineage-specific survival, as we suggest here) the possibility of other mechanisms, such as lineage-specific movement of cells, during blastulation. Ethical considerations, however, make investigating this mechanism difficult on human embryos. WIDER IMPLICATIONS OF THE FINDINGS: Mosaic human cleavage-stage embryos can differentiate into a euploid ICM where euploid cell populations predominate. Sequestering of aneuploid cells/nuclei to structures no longer involved in fetal development has important implications for preimplantation and prenatal genetic testing. These results also challenge previous fundamental understandings of mitotic fidelity in early human development and indicate a complex and fluid nature of the human embryonic genome. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by Organon Pharmaceuticals and Merck Serono by grants to W.G.K. W.G.K. is also an employee of AdvaGenix, who could, potentially, indirectly benefit financially from publication of this manuscript. R.C.M. is supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number R35GM133747. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. D.K.G. provides paid consultancy services for Care Fertility. TRIAL REGISTRATION NUMBER: : N/A.

Newly isolated halotolerant Aspergillus sp. showed high diesel degradation efficiency under high salinity environment aided with hematite.

The contamination of saline soil with hazardous petroleum hydrocarbons is a common problem across coastal areas globally. Bioaugmentation combined with chemical treatment is an emerging remediation technique, but it currently shows low efficiency under high saline environments. In this study, we screened and used a novel halotolerant lipolytic fungal consortium (HLFC) combined with hematite (Fe2O3) for the bioremediation of diesel contaminated saline soils. The changes in total petroleum hydrocarbons (TPH) concentrations, enzyme activity, and microbial diversity were compared among different treatments (HLFC, hematite, hematite-HLFC, and control). The results showed that TPH degradation was significantly (P < 0.05) enhanced in hematite-HLFC (47.59-88.01%) and HLFC (24.26-72.04%) amended microcosms across all salinity levels, compared to the treatments of hematite (23.71-66.26%) and control (6.39-55.20%). TPH degradation was positively correlated with lipase and laccase enzyme activities, electrical conductivity, and the water holding capacity of the soil. Analyses of the microbial community structure showed that microbial richness decreased, while evenness increased in HLFC and hematite-HLFC treatments. The relative abundances of Alicyclobacillus, Sediminibacillus, Alcanivorax, Penicillium, Aspergillus, and Candida genera were significantly high in hematite-HLFC and HLFC amended microcosms. Our findings provide a promising new microbial-based technique, which can degrade TPH efficiently in saline soil.

Women With a History of Primary Infertility and Increased Rates of Bilateral Oophorectomy.

OBJECTIVE: To evaluate the association of primary infertility with subsequent bilateral oophorectomy and hysterectomy, using a population-based cohort of women with primary infertility and age-matched women in a referent group. METHODS: The Rochester Epidemiology Project record-linkage system was used to assemble a population-based cohort of women with primary infertility diagnosed between 1980 and 1999 (index date). Women were age-matched (±1 year) 1:1 to women without a history of infertility or hysterectomy at the index date (referent group). Cox proportional hazards models were fit to compare long-term risks of bilateral oophorectomy and hysterectomy, respectively, between women with infertility and women in the referent group. RESULTS: Among both groups of 1,001 women, the mean age at the index date was 29.2±4.4 years. Median duration of follow-up was 23.7 years for both groups. Women with primary infertility were 1.7 times (adjusted hazard ratio [aHR] 1.69, 95% CI 1.22-2.33) more likely to undergo bilateral oophorectomy compared with women in the referent group. In a sensitivity analysis that excluded women with a diagnosis of infertility related to endometriosis and their matched referent group participants, this association persisted (aHR 1.50, 95% CI 1.06-2.14). Women with primary infertility did not have a significant increased risk of hysterectomy (aHR 0.98, 95% CI 0.79-1.23). However, risk of hysterectomy was increased in those with primary infertility related to endometriosis (aHR 1.94, 95% CI 1.12-3.34). We observed that women with primary infertility were more likely to undergo hysterectomy with bilateral oophorectomy. Women in the referent group were more likely to undergo hysterectomy with ovarian conservation. Few women in either group had isolated bilateral oophorectomy. CONCLUSION: Primary infertility, with and without a diagnosis of endometriosis, is associated with an increased risk of bilateral oophorectomy. In women with endometriosis-related infertility, there is an association with future hysterectomy. These findings represent important confounders in the evaluation of long-term health outcomes related to primary infertility.

Distinctions in PCOS Induced by Letrozole Vs Dehydroepiandrosterone With High-fat Diet in Mouse Model.

Polycystic ovarian syndrome (PCOS) is a complex health condition associated with metabolic disturbances and infertility. Recent data suggest that the prevalence of PCOS is increasing among women globally, although the etiology of these trends is undefined. Consequently, preclinical models that better reflect the biology of PCOS are urgently needed to facilitate research that can lead to the discovery of prevention strategies or improved management. The existing animal models have several limitations as they do not reflect all the PCOS features metabolically and/or phenotypically. Therefore, there is no clear consensus on the use of appropriate animal model and selection of the most appropriate PCOS-inducing agent. To that end, we have established a Swiss albino mouse model of PCOS based on 3 weeks of daily treatment with letrozole (50 µg/day; intraperitoneal) and dehydroepiandrosterone (DHEA, 6 mg/100 g body weight; subcutaneous) in 5-week-old female mice fed on normal or high-fat diet (HFD). Mice were regularly assessed for body weight, blood glucose, and estrous cycle. Three weeks after drug administration, mice were sacrificed and assessed for blood-based metabolic parameters as well as ovarian function. Our results indicate that DHEA combined with HFD produces changes mimicking those of clinical PCOS, including elevated serum testosterone and luteinizing hormone, dyslipidemia, poor ovarian microenvironment, and development of multiple ovarian cysts, recapitulating cardinal features of PCOS. In comparison, normal diet and/or letrozole produced fewer features of PCOS. The data from the experimental models presented here can improve our understanding of PCOS, a growing concern in women's health.

MAPK Signaling Pathway Is Essential for Female Reproductive Regulation in the Cabbage Beetle, Colaphellus bowringi.

The mitogen-activated protein kinase (MAPK) signaling pathway is a well-conserved intracellular signal transduction pathway, and has important roles in mammalian reproduction. However, it is unknown whether MAPK also regulates insect reproductive mechanisms. Therefore, we investigated the role of the MAPK signaling pathway in ovarian growth and oviposition in the cabbage beetle Colaphellus bowringi, an economically important pest of Cruciferous vegetables. As an initial step, 14 genes from the extracellular regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK (P38) cascades were knocked down using RNA interference (RNAi). The results revealed that RNAi knockdown of MAPK-ERK kinase (MEK), ERK, Kinase suppressor of RAS 2 (KSR2), and P38 induced ovarian development stagnation, low fecundity, and decreased longevity, which indicate that ERK and P38 signaling pathways are important for female C. bowringi survival and reproduction. The potential regulatory role of ERK and P38 pathways in the female reproductive process was investigated using quantitative real-time PCR. We found that ERK pathway possibly regulated ecdysone biosynthesis and P38 pathway possibly involved in the germline stem cell (GSC) development and differentiation. Our findings demonstrated the importance of the MAPK signaling pathway in the female reproduction of insects, and further enhanced the molecular mechanism of female reproductive regulation in insects.

Effects of Koumiss on Intestinal Immune Modulation in Immunosuppressed Rats.

Koumiss is a traditional fermented dairy product with health and medicinal benefits. It is very popular in the Inner Mongolia Autonomous Region of China. The results of relevant studies have shown that koumiss can regulate the gastrointestinal environment, improve the absorption of nutrients, improve the body's intolerance to lactose, enhance the body's immunity, prevent scurvy and atherosclerosis, and aid in the treatment of tuberculosis. However, there are no systematic reports on the effects of koumiss on immunity. In this study, we aimed to decipher the effects of koumiss on intestinal immune modulation. We used liquid chromatography-tandem mass spectrometry (LC-MS) analysis to determine the composition of Koumiss. Using Compound Discoverer software, we compared the mass spectrometry data with the compound information in the online databases ChemSpider and mzCloud to intelligently identify the main chemical components of koumiss. Additionally, we used Mass Frontier small molecule fragmentation libraryTM to determine the structure of fragment ions. A total of 21 components were identified, which clarified the chemical basis of koumiss. These 21 compounds were then used to perform molecular docking with immune-related targets, such as TNF, IL2, IL10, etc. The results indicated good docking activity between most of the compounds and the targets. Then, an immunosuppressive rat model was used to determine the therapeutic effect of koumiss. The results of this study showed that koumiss could, to a certain extent, correct the atrophy of the thymus and spleen in immunosuppressed model rats. The number of leukocytes, lymphocytes, and the CD4+/CD8+ ratio of peripheral blood lymphocytes was also increased. In addition, it could effectively improve the structure of the small intestinal mucosa, which shows that koumiss has a positive effect on the intestinal immune function of immunosuppressed rats. These findings provide an experimental basis for the development and utilization of koumiss as a therapeutic product.

Fertility trends and comparisons in a historical cohort of US women with primary infertility.

BACKGROUND: There is growing interest in long-term outcomes following infertility and infertility treatment. However, there are few detailed longitudinal cohorts available for this work. This study aimed to assemble a historical cohort of women with primary infertility and age-matched controls to evaluate fertility trends, sequelae, and sociodemographic differences. Described here are cohort group characteristics and associated reproductive trends over time. METHODS: A population-based historical cohort was created using the Rochester Epidemiology Project (REP) record-linkage system (Olmsted County, MN). The cohort included women aged 18-50 with a diagnosis of primary infertility between January 1, 1980, and December 31, 1999. As part of a case-control study, we identified 1:1 age-matched female controls from the same community and era. RESULTS: A total of 1001 women with primary infertility and 1001 age-matched controls were identified. The women with primary infertility were significantly more likely to be married, college educated, use barrier contraception, and non-smokers compared to age-matched controls. The incidence of primary infertility increased from 14 to 20 per 10,000 person years from 1980-1985 to 1995-1999. Ovulatory dysfunction and unexplained infertility were the most common causes of primary infertility and clomiphene was the most widely used fertility medication. Rates of in vitro fertilization (IVF) increased from 1.8% during 1980-1985 to 26.0% during 1995-1999. CONCLUSION: Women with primary infertility were found to have unique sociodemographic characteristics compared to age-matched control women, which is consistent with previous research. The incidence of diagnosed primary infertility increased from 1980 to 1999, as did use of IVF.

This study aimed to assemble a historic cohort of women with primary infertility and age-matched control women. The cohort included 1001 women with primary infertility diagnosed between 1980 and 1999 and 1001 age-matched controls from the same community and era. This cohort demonstrated baseline differences between the primary infertility and control groups, including differences in marital status, education, use of barrier contraception and smoking status. Additionally, the cohort showed an increased incidence in diagnosis of primary infertility from 1980 to 1999. Creation of this cohort will enable future research focused on long-term outcomes following primary infertility diagnosis and treatment.

Outcomes of embryo transfers performed by Reproductive Endocrinology and Infertility fellows vs. faculty: an 11-year retrospective review.

OBJECTIVE: To compare the clinical pregnancy rate (CPR) and live birth rate (LBR) of embryo transfer episodes (ETEs) performed by Reproductive Endocrinology and Infertility fellows vs. those of ETEs performed by faculty physicians. DESIGN: Retrospective cohort analysis. SETTING: Academic reproductive endocrinology and infertility practice. PATIENT(S): In total, 3,073 ETEs for 1,488 unique patients were performed by fellows or faculty physicians between January 2009 and January 2020. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate and LBR. RESULT(S): Fifteen fellows performed 1,225 (39.9%) of 3,073 ETEs after completing 30 mock transfers. On comparing outcomes among fellowship years (FY1, FY2, and FY3), CPR (44.1% vs. 43.2% vs. 45.7%, respectively, P = .83) and LBR (39.1% vs. 38.1% vs. 38.4%, respectively, P = .97) were not significantly different. Fellowship year 1 fellows' initial 30 ETEs vs. all the remaining FY1 ETEs had a significantly higher CPR (48.1% vs. 40.5%, respectively, P = .030) and LBR (45.4% vs. 34.3%, respectively, P = .001). There were no significant differences between faculty versus fellow ETEs in terms of CPR (43.0% vs. 45.0%, respectively, P = .30) or LBR (37.3% vs. 39.8%, respectively, P = .16), even after adjusting for patient age, body mass index, primary infertility diagnosis, autologous vs. donor oocyte, fresh vs. frozen embryo, number of embryos transferred, type of transfer catheter, and year of transfer (P = .32 for CPR, P = .22 for LBR). CONCLUSION(S): Appropriately trained FY1 fellows had success rates maintained throughout all FYs. There were no significant differences in clinical outcomes between fellow- and faculty-performed transfers. These data demonstrated that allowing fellows to perform live embryo transfers is not detrimental to clinical outcomes.