Intramolecular Hydrogen Bonds Assisted Construction of Planar Tricyclic Structures for Insensitive and Highly Thermostable Energetic Materials.

Safety is fundamental for the practical development and application of energetic materials. Three tricyclic energetic compounds, namely, 1,3-di(1H-tetrazol-5-yl)-1H-1,2,4-triazol-5-amine (ATDT), 5'-nitro-3-(1H-tetrazol-5-yl)-2'H-[1,3'-bi(1,2,4-triazol)]-5-amine (ATNT), and 1-(3,4-dinitro-1H-pyrazol-5-yl)-3-(1H-tetrazol-5-yl)-1H-1,2,4-triazol-5-amine (ATDNP), were effectively synthesized through a simple two-step synthetic route. The introduction of intramolecular hydrogen bonds resulted in excellent molecular planarity for the three new compounds. Additionally, they exhibit regular crystal packing, leading to numerous intermolecular hydrogen bonds and π-π interactions. Benefiting from planar tricyclic structural features, ATDT, ATNT, and ATDNP are insensitive (IS > 60 J, FS = 360 N) when exposed to external stimuli. Furthermore, ATNT (Td = 361.1 °C) and ATDNP (Td = 317.0 °C) exhibit high decomposition temperatures and satisfying detonation performance. The intermolecular hydrogen bonding that produced this planar tricyclic molecular structure serves as a model for the creation of innovative multiple heterocycle energetic materials with excellent stability.

The HEAT repeat protein HPO-27 is a lysosome fission factor.

Lysosomes are degradation and signalling centres crucial for homeostasis, development and ageing1. To meet diverse cellular demands, lysosomes remodel their morphology and function through constant fusion and fission2,3. Little is known about the molecular basis of fission. Here we identify HPO-27, a conserved HEAT repeat protein, as a lysosome scission factor in Caenorhabditis elegans. Loss of HPO-27 impairs lysosome fission and leads to an excessive tubular network that ultimately collapses. HPO-27 and its human homologue MROH1 are recruited to lysosomes by RAB-7 and enriched at scission sites. Super-resolution imaging, negative-staining electron microscopy and in vitro reconstitution assays reveal that HPO-27 and MROH1 self-assemble to mediate the constriction and scission of lysosomal tubules in worms and mammalian cells, respectively, and assemble to sever supported membrane tubes in vitro. Loss of HPO-27 affects lysosomal morphology, integrity and degradation activity, which impairs animal development and longevity. Thus, HPO-27 and MROH1 act as self-assembling scission factors to maintain lysosomal homeostasis and function.

Ethical leadership and TMT decision-making of corporate social responsibility - a perspective of self-determination theory.

This study examines the impact of ethical leadership on top management team (TMT) decision-making regarding corporate social responsibility (CSR), considering the mediating role of TMT passion and the moderating role of performance stress. The study distinguishes between TMT harmonious and obsessive work passion and categorizes CSR as proactive and reactive. The findings reveal the following: (1) Ethical leadership positively influences proactive CSR, with TMT harmonious work passion acting as a positive mediator and TMT obsessive work passion playing a negative mediating role; (2) ethical leadership positively affects reactive CSR, with both TMT harmonious and obsessive work passion serving as positive mediators; (3) performance stress diminishes the impact of ethical leadership on TMT harmonious work passion; however, it amplifies the effect on TMT obsessive work passion. Consequently, the mediating effect of TMT harmonious work passion weakens, while the mediating effect of TMT obsessive work passion strengthens. This study emphasizes the significant role of TMT in CSR strategic decision-making and proposes a novel mediating mechanism through which ethical leadership drives CSR decision-making by considering TMT work passion. These findings reconcile the theoretical-practical conflict and have important theoretical and practical implications for enterprises in fulfilling their social responsibility.

Multilayer Perceptron Algorithm-Assisted Flexible Piezoresistive PDMS/Chitosan/cMWCNT Sponge Pressure Sensor for Sedentary Healthcare Monitoring.

Recently, the health problems faced by sedentary workers have received increasing attention. In this study, a pressure sensor based on a poly(dimethylsiloxane) (PDMS)/carboxylated chitosan (CCS)/carboxylated multiwalled carbon nanotube (cMWCNT) sponge was prepared to realize a portable, sensitive, comfortable, and noninvasive healthcare monitoring system for sedentary workers. The proposed piezoresistive pressure sensor exhibited exceptional sensing performances with high sensitivity (147.74 kPa-1), an ultrawide detection range (22 Pa to 1.42 MPa), and reliable stability (over 3000 cycles). Furthermore, the obtained sensor displayed superior capability in detecting various human motion signals. Based on the 4 × 4 sensing array and multilayer perceptron (MLP) algorithm model, a smart cushion was developed to recognize five types of sitting postures and supply timely reminders to sedentary workers. The piezoresistive sponge pressure sensor proposed in this study reveals promising potential in the fields of wearable electronics, healthcare monitoring, and human-machine interface applications.

TPOAb positivity can impact ovarian reserve, embryo quality, and IVF/ICSI outcomes in euthyroid infertile women.

The aim of this study was to investigate the effects of positive anti-thyroid peroxidase (TPO) antibodies on fertility, embryo quality, and pregnancy outcomes in women with normal thyroid function. A cross-sectional study of 1223 infertile women who received assisted reproductive technology (ART) treatment for the first time was conducted at our hospital from January 2019 to March 2022. Overall, 263 infertile women were included, comprising 263 cycles and 1813 embryos, and were divided into a positive group and a control group based on TPO antibody levels. The positive group was further divided into two subgroups according to the median antibody titer, and the therapeutic indices and pregnancy outcomes for each group were compared. The results showed that the AMH level in the positive group was significantly lower than that in the control group (2.37 (1.26-3.63) ng/ml vs. 3.54 (1.74-5.41) ng/ml, p < 0.001). The high-quality embryo rate (40.04% vs. 45.49%, p = 0.034) and live birth rate (23.26% vs. 36.16, p = 0.035) of the positive group were lower than those of the control group; the miscarriage rate was higher than that of the control group (37.50% vs. 17.95%, p = 0.035). The live birth rate in the low-titer group was significantly higher than that in the high-titer group (32.56% vs. 13.95%, p = 0.041). Studies have shown that positive anti-thyroid peroxidase antibodies are associated with a decreased ovarian reserve and decreased embryo quality. High titers of anti-thyroid peroxidase antibodies can reduce the live birth rate.

Increased serine synthesis in cumulus cells of young infertile women with diminished ovarian reserve.

STUDY QUESTION: What are the differences in gene expression of cumulus cells (CCs) between young women with diminished ovarian reserve (DOR) and those of similar age with normal ovarian reserve (NOR)? SUMMARY ANSWER: Gene expression and metabolome profiling analysis demonstrate that the de novo serine synthesis pathway (SSP) is increased in the CCs of young women with DOR. WHAT IS KNOWN ALREADY: The incidence of DOR has risen, tending to present at younger ages. Its mechanisms and aetiologies are still poorly understood. Abnormal metabolism is present in luteinized CCs of patients with DOR. Previous studies have revealed that mitochondrial dysfunction and impaired oxidative phosphorylation in CCs are related to DOR in women of advanced age. The pathogenic mechanisms likely differ between young women with DOR and cases associated with advanced maternal age. Several studies have examined amino acid metabolism in the follicle, with a focus on embryo development, but less information is available about CCs. The physiological significance of de novo serine synthesis in follicles and oocytes remains largely unknown. STUDY DESIGN, SIZE, DURATION: CC samples were obtained from 107 young infertile women (age <38 years) undergoing ICSI, from July 2017 to June 2019, including 54 patients with DOR and 53 patients with NOR. PARTICIPANTS/MATERIALS, SETTING, METHODS: Oocyte development data were analysed retrospectively. Comprehensive genome-wide transcriptomics of CCs was performed. Differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to categorize the functions of the DEGs and identify significantly enriched pathways. The transcript and protein levels of key enzymes involved in serine synthesis were verified in additional samples using quantitative real-time PCR (qRT-PCR) (n = 10) and capillary western blotting (n = 36). Targeted metabolomics of amino acids in CC extracts was performed by ultrahigh-performance liquid MS (UHPLC-MS/MS). MAIN RESULTS AND THE ROLE OF CHANCE: The number of oocytes (2.4 ± 2.2 versus 12.1 ± 5.3) and metaphase II oocytes (2.1 ± 2.0 versus 9.9 ± 4.9) retrieved was significantly decreased in the DOR versus the NOR group, respectively (P < 0.0001). The rates of fertilization (80.7% versus 78.8%), viable embryos (73.7% versus 72.5%), and high-quality embryos (42.8% versus 49.0%) did not differ between the DOR and NOR groups, respectively (P > 0.05). A total of 95 DEGs were found by transcriptome sequencing. GO and KEGG analyses demonstrated that the DEGs were linked to amino acid metabolism and suggested significantly higher activity of the de novo SSP in the CCs of young women with DOR. Further qRT-PCR and capillary western blotting revealed that key enzymes (PHGDH, PSAT1, PSPH, and SHMT2) involved in de novo serine synthesis were upregulated, and UHPLC-MS/MS analysis showed increases in serine and glycine (a downstream product of serine) levels in the CCs of young patients with DOR. Our data clearly demonstrate that the de novo SSP, which diverts 3-phosphoglycerate from glycolysis to serine synthesis, was upregulated in young DOR CCs. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Regarding the reproductive capacity of young patients DOR, the pregnancy outcomes were not analysed. The sample size was limited, and only women undergoing ICSI were examined since this was a prerequisite for the acquisition of CCs, which may cause selection bias. The exact mechanisms by which the SSP in CCs regulates ovarian reserve still require further study. WIDER IMPLICATIONS OF THE FINDINGS: Our research presents new evidence that alterations of the SSP in CCs of young infertile women are associated with DOR. We believe this is a significant contribution to the field, which should be key for understanding the cause and mechanisms of ovarian hypofunction in young women. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the Ministry of Science and Technology of China (2018YFC1005001) and National Natural Science Foundation of China (31601197). There were no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Plasma-Induced Formation of Pt Nanoparticles with Optimized Surface Oxidation States for Methanol Oxidation and Oxygen Reduction Reactions to Achieve High-Performance DMFCs.

Plasma treatment and reduction are used to synthesize Pt nanoparticles (NPs) on nitrogen-doped carbon nanotubes (p-Pt/p-NCNT) with a low Pt content. In particular, the plasma treatment is used to treat the NCNT to give it with more surface defects, facilitating a better growth of the Pt NPs, while the plasma reduction produces the Pt NPs with a reduced fraction of the surface atoms at the high oxidation states, increasing the catalytic activities of the p-Pt@p-NCNT. Even at the low Pt content (7.8 wt.%), the p-Pt@p-NCNT shows superior catalytic activities and good stabilities for methanol oxidation reaction (MOR) and oxygen reduction reaction (ORR). The density functional theory (DFT) calculations indicate that the defects generated in the plasma treatment can help the growth of the Pt NPs on the NCNTs, leading to the stronger electronic coupling between Pt and NCNT and the increased stability of the catalyst. The plasma reduction can give the Pt NPs with optimized surface oxidation states, decreasing the energy barriers of the rate-determining steps for MOR and ORR. When used as the anode and cathode catalysts for the direct methanol fuel cells (DMFCs), the p-Pt@p-NCNT exhibits a higher maximum power density of 81.9 mW cm-2  at 80 °C and shows good durability.

Early postnatal defects in neurogenesis in the 3xTg mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder leading to dementia. The hippocampus, which is one of the sites where neural stem cells reside and new neurons are born, exhibits the most significant neuronal loss in AD. A decline in adult neurogenesis has been described in several animal models of AD. However, the age at which this defect first appears remains unknown. To determine at which stage, from birth to adulthood, the neurogenic deficits are found in AD, we used the triple transgenic mouse model of AD (3xTg). We show that defects in neurogenesis are present as early as postnatal stages, well before the onset of any neuropathology or behavioral deficits. We also show that 3xTg mice have significantly fewer neural stem/progenitor cells, with reduced proliferation and decreased numbers of newborn neurons at postnatal stages, consistent with reduced volumes of hippocampal structures. To determine whether there are early changes in the molecular signatures of neural stem/progenitor cells, we perform bulk RNA-seq on cells sorted directly from the hippocampus. We show significant changes in the gene expression profiles at one month of age, including genes of the Notch and Wnt pathways. These findings reveal impairments in neurogenesis very early in the 3xTg AD model, which provides new opportunities for early diagnosis and therapeutic interventions to prevent neurodegeneration in AD.

Initial stage of carbonization of iron during hydrocarbons dissociation: a molecular dynamics study.

The carbonization of iron is a very important early phenomenon in the field of heterogeneous catalysis and the petrochemical industry, but the mechanism is still controversial. In this work, the carbonization mechanism and carbonization structure of iron nanoparticles by different carbon sources (CH4, C2H6, C2H4, C2H2) were systematically investigated using the reactive molecular dynamics method. The results show that saturated alkanes are dehydrogenated while adsorbed, but unsaturated olefins and alkynes undergo bond-breaking while adsorbed. The C-H bond is more likely to break than the C-C bond. Hydrocarbons with high carbon content have a strong ability to carbonize Fe nanoparticles under the same conditions. For C2H4 and C2H2, the C atoms generated from dissociation form a large number of long carbon chains intertwined with branched chains and multiple carbon rings. The C2 species formed by C2H2 after complete dehydrogenation diffuse rapidly to the interior of the nanoparticles, releasing the surface active sites and accelerating the carbonization process. Carbon-rich iron carbides (FeCx) with different Fe/C ratios were obtained by carbonization with different carbon sources. In addition, the Fe(110) surface exhibits the strongest carburizing ability. These findings provide systematic insights into the initial stages of metal Fe carburization.

Metal-Free Electrochemically Reductive Deuteration of C═N Bonds with D2O toward Deuterated Amines.

Environmentally friendly and highly efficient synthesis of α-deuterated amines is achieved via a concise electrochemical process using D2O as deuterium source without any external reductants or catalysts. Various imines are compatible, affording the desired products in high yields and D-incorporation. Gram-scale synthesis and flow-cell electrochemistry technology are used to synthesize deuterated pharmaceutical amines and their intermediates. Mechanistic studies reveal a plausible process, including the formation of carbanion species followed by deuterium atom transfer.

Effect of advanced paternal age on reproductive outcomes in IVF cycles of non-male-factor infertility: a retrospective cohort study.

Advanced paternal age has been overlooked, and its effect on fertility remains controversial. Previous studies have focused mainly on intracytoplasmic sperm injection (ICSI) cycles in men with oligozoospermia. However, few studies have reported on men with semen parameters within reference ranges. Therefore, we conducted a retrospective cohort study analyzing the reproductive outcomes of couples with non-male-factor infertility undergoing in vitro fertilization (IVF) cycles. In total, 381 cycles included were subgrouped according to paternal age (<35-year-old, 35-39-year-old, or ≥40-year-old), and maternal age was limited to under 35 years. Data on embryo quality and clinical outcomes were analyzed. The results showed that fertilization and high-quality embryo rates were not significantly different (all P > 0.05). The pregnancy rate was not significantly different in the 35-39-year-old group (42.0%; P > 0.05), but was significantly lower in the ≥40-year-old group (26.1%; P < 0.05) than that in the <35-year-old group (40.3%). Similarly, the implantation rate significantly decreased in the ≥40-year-old group (18.8%) compared with that in the <35-year-old group (31.1%) and 35-39-year-old group (30.0%) (both P < 0.05). The live birth rate (30.6%, 21.7%, and 19.6%) was not significantly different across the paternal age subgroups (<35-year-old, 35-39-year-old, and ≥40-year-old, respectively; all P > 0.05), but showed a declining trend. The miscarriage rate significantly increased in the 35-39-year-old group (44.8%) compared with that in the <35-year-old group (21.0%; P < 0.05). No abnormality in newborn birth weight was found. The results indicated that paternal age over 40 years is a key risk factor that influences the assisted reproductive technology success rate even with good semen parameters, although it has no impact on embryo development.

Effects of Heavy Metal Stress on Physiology, Hydraulics, and Anatomy of Three Desert Plants in the Jinchang Mining Area, China.

The physiological mechanisms and phytoremediation effects of three kinds of native quinoa in a desert mining area were studied. We used two different types of local soils (native soil and tailing soil) to analyze the changes in the heavy metal content, leaf physiology, photosynthetic parameters, stem hydraulics, and anatomical characteristics of potted quinoa. The results show that the chlorophyll content, photosynthetic rate, stomatal conductance, and transpiration rate of Kochia scoparia were decreased, but intercellular CO2 concentration (Ci) was increased under heavy metal stress, and the net photosynthetic rate (Pn) was decreased due to non-stomatal limitation. The gas exchange of Chenopodium glaucum and Atriplex centralasiatica showed a decrease in Pn, stomatal conductance (Gs), and transpiration rate (E) due to stomatal limitation. The three species showed a similar change in heavy metal content; they all showed elevated hydraulic parameters, decreased vessel density, and significantly thickened vessel walls under heavy metal stress. Physiological indicators such as proline content and activity of superoxide dismutase (SOD) and peroxidase (POD) increased, but the content of malondialdehyde (MDA) and glutathione (GSH), as well as catalase (CAT) activity, decreased in these three plants. Therefore, it can be concluded that these three species of quinoa, possibly the most dominant 30 desert plants in the region, showed a good adaptability and accumulation capacity under the pressure of heavy metal stress, and these plants can be good candidates for tailings remediation in the Jinchang desert mining area.

Phytoremediation Potential and Physiological Mechanisms Underlying Metallic Extraction of Suaeda glauca, Artemisia desertorum, and Atriplex canescens.

Mining activities have led to serious environmental (soil erosion, degradation of vegetation, and groundwater contamination) and human health (musculoskeletal problems, diarrheal conditions, and chronic diseases) issues at desert mining areas in northwest China. Native plant species grown naturally in desert regions show a unique tolerance to arid and semiarid conditions and are potential candidates for soil phytoremediation. Here, an ex situ experiment involving pot planting of seedlings of three native plant species (Suaeda glauca, Artemisia desertorum, and Atriplex canescens) was designed to explore their phytoremediation potential and the underlying physiological mechanism. For Zn and Cu, the three plants were all with a biological accumulation coefficient (BAC) greater than 1. For Cd, Ni, and Pb, Atriplex canescens had the highest bioaccumulation concentrations (521.52, 862.23, and 1734.59 mg/kg), with BAC values (1.06, 1.30, 1.25) greater than 1, which indicates that Atriplex canescens could be a broad-spectrum metal extraction plant. Physiological analysis (antioxidation, extracellular secretions, photosynthesis, and hydraulics) showed that the three desert plants exploited their unique strategy to protect against the stress of complex metals in soils. Moreover, the second growing period was the main heavy metal accumulation and extraction stage concomitant with highest water use efficiency (iWUE). Taken together, the three desert plants exhibited the potent heavy metal extraction ability and physiological and ecological adaptability to a harsh polluted environment in arid desert areas, providing potential resources for the bioremediation of metal-contaminated soils in an arid and semiarid desert environment.

Role of pyroglutamic acid in cumulus cells of women with polycystic ovary syndrome.

PURPOSE: Polycystic ovary syndrome is a complex heterogeneous endocrine disorder associated with established metabolic abnormalities and is a common cause of infertility in females. Glutathione metabolism in the cumulus cells (CCs) of women with PCOS may be correlated to the quality of oocytes for infertility treatment; therefore, we used a metabolomics approach to examine changes in CCs from women with PCOS and oocyte quality. METHODS: Among 135 women undergoing fertility treatment in the present study, there were 43 women with PCOS and 92 without. CCs were collected from the two groups and levels of pyroglutamic acid were measured using LC-MS/MS followed by qPCR and Western blot analysis to examine genes and proteins involved in pyroglutamic acid metabolism related to glutathione synthesis. RESULTS: Women with PCOS showed increased levels of L-pyroglutamic acid, L-glutamate, and L-phenylalanine and decreased levels of Cys-Gly and N-acetyl-L-methionine. Gene expression of OPLAH, involved in pyroglutamic synthesis, was significantly increased in women with PCOS compared with those without. Gene expression of GSS was significantly decreased in women with PCOS and synthesis of glutathione synthetase protein was decreased. Expression of nuclear factor erythroid 2-related factor 2, involved in resistance to oxidative stress, was significantly increased in women with PCOS. CONCLUSIONS: CCs of women with PCOS showed high concentrations of pyroglutamic acid and reduced glutathione synthesis, which causes oxidative stress in CCs, suggesting that decreased glutathione synthesis due to high levels of pyroglutamic acid in CCs may be related to the quality of oocytes in women with PCOS.

Tri-explosophoric groups driven fused energetic heterocycles featuring superior energetic and safety performances outperforms HMX.

The design and synthesis of novel energetic compounds with integrated properties of high density, high energy, good thermal stability and sensitivities is particularly challenging due to the inherent contradiction between energy and safety for energetic compounds. In this study, a novel structure of 4-amino-7,8-dinitropyrazolo-[5,1-d] [1,2,3,5]-tetrazine 2-oxide (BITE-101) is designed and synthesized in three steps. With the help of the complementary advantages of different explosophoric groups and diverse weak interactions, BITE-101 is superior to the benchmark explosive HMX in all respects, including higher density of 1.957 g·cm-3, highest decomposition temperature of 295 °C (onset) among CHON-based high explosives to date and superior detonation velocity and pressure (D: 9314 m·s-1, P: 39.3 GPa), impact and friction sensitivities (IS: 18 J, FS: 128 N), thereby showing great potential for practical application as replacement for HMX, the most powerful military explosive in current use.

Recent progress on covalent organic framework materials as CO2 reduction electrocatalysts.

CO2 emission caused by fuel combustion and human activity has caused severe climate change and other subsequent pollutions around the world. Carbon neutralization via various novel technologies to alleviate the CO2 level in the atmosphere has thus become one of the major topics in modern research field. These advanced technologies cover CO2 capture, storage and conversion, etc., and electrocatalytic CO2 reduction reaction (CO2RR) by heterogeneous catalysts is among the most promising methods since it could utilize renewable energy and generate valuable fuels and chemicals. Covalent organic frameworks (COFs) represent crystalline organic polymers with highly rigid, conjugated structures and tunable porosity, which exhibit significant potential as heterogeneous electrocatalysts for CO2RR. This review briefly introduces related pioneering works in COF-based materials for electrocatalytic CO2RR in recent years and provides a basis for future design and synthesis of highly active and selective COF-based electrocatalysts in this direction.

Energetic Gem-dinitro Salts with Improved Thermal Stability by Incorporating with A Fused Building Block.

Thermal stability is one of the most significant properties for the safety of energetic materials, finding a stable skeleton with suitable energetic groups is always a primary test. In this work, an unusual aminohydrazone cyclization strategy was used in the synthesis of a new series of gem-dinitro 1,2,4-triazolo[4,3-b][1,2,4,5]-tetrazine compounds with desirable thermal stability (≥197 °C). All of the new compounds were fully characterized by infrared (IR), NMR, differential scanning calorimetry, single crystal X-ray diffraction, and elemental analysis. The decomposition temperature of potassium salt 2 is 288 °C, reaching the level of HMX. All of these performances have demonstrated the effective synthesis strategy for innovatively combining geminal dinitro groups with fused rings.

Dysregulated sphingolipid metabolism and autophagy in granulosa cells of women with endometriosis.

We evaluated metabolic profiles between cumulus cells (CCs) and mural granulosa cells (MGCs) derived from women with endometriosis to identify their correlations with oocyte quality. CCs and MGCs were collected from women with and without endometriosis undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. The metabolomics of CCs and MGCs were measured by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) followed by a quantitative polymerase chain reaction to further confirm the genes involved in the metabolic results. LC-MS/MS analysis revealed differences in 24 metabolites of CCs and 71 metabolites of MGCs between groups. Among them, five metabolites were upregulated and 19 metabolites were downregulated in CCs with endometriosis, whereas three metabolites were upregulated and 68 metabolites were downregulated in MGCs with endometriosis. Metabolites related to sphingolipid metabolism, which included palmitic acid (PA) and docosahexaenoic acid, increased significantly only in CCs with endometriosis, whereas sphingosine and PA were significantly downregulated in MGCs with endometriosis compared with CCs and MGCs without endometriosis. Gene expression involved in ceramide synthesis (CERS1, SPTL1, and SMPD1) and autophagy (BECN1, LAMP, and PC3) were significantly higher in CCs with endometriosis according to FASN, BECN1, and LAMP protein expressions. However, gene expression involved in ceramide synthesis (SPHK1, ASAH1, and SGPP1) and autophagy (BECN1, LAMP, and PC3) were significantly lower in MGCs with endometriosis, whereas CERS1 and UGCG expression increased. There are differences in sphingolipid metabolites in CCs and MGCs with endometriosis compared with women without endometriosis. These differences seem to be involved in the regulation of autophagic cell death in preovulatory follicles.

Mitochondrial dysfunction in cumulus cells is related to decreased reproductive capacity in advanced-age women.

OBJECTIVE: To reveal the relationship between mitochondrial function in cumulus cells (CCs) and the aging-related decline in ovarian function and reproductive capacity. DESIGN: Retrospective and transcriptome analysis of human tissue. SETTING: University hospital. PATIENT(S): A total of 186 infertile women with normal weight and no other diseases, including 86 young women (aged <38 years) with normal ovarian reserve and 100 advanced-age women (aged ≥38 years) with diminished ovarian reserve. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Embryo development data were analyzed. The mitochondrial ultrastructure of CCs was observed by transmission electron microscopy. Mitochondrial activity was detected by immunofluorescence. The per-CC mitochondrial deoxyribonucleic acid copy numbers and cellular adenosine triphosphate levels were quantified. Unbiased comprehensive genome-wide transcriptomics was performed. The functions of all annotated genes and biologic pathways were analyzed by the Kyoto Encyclopedia of Genes and Genomes. RESULT(S): Advanced-age women with diminished ovarian function had significantly fewer retrieved oocytes and lower embryo quality. The normal mitochondrial rate in CCs was significantly lower. In addition to mitochondrial morphology and structural changes, the fluorescence intensity of Fluo-3/AM was significantly higher, and that of MitoTracker was lower than that of young women with normal ovarian reserve, suggesting that age negatively affects the mitochondrial activity of CCs. The per-CC mitochondrial deoxyribonucleic acid copy number and adenosine triphosphate levels significantly decreased in the advanced-age group. The Kyoto Encyclopedia of Genes and Genomes analysis showed that differentially expressed genes were significantly enriched in the oxidative phosphorylation pathway. Additionally, most mitochondrially encoded genes related to oxidative phosphorylation were significantly down-regulated in the advanced-age group. CONCLUSION(S): We present current evidence that mitochondrial dysfunction in CCs may play a key role in the age-related decline in ovarian function and reproductive capacity.

Deep learning for microscopic examination of protozoan parasites.

The infectious and parasitic diseases represent a major threat to public health and are among the main causes of morbidity and mortality. The complex and divergent life cycles of parasites present major difficulties associated with the diagnosis of these organisms by microscopic examination. Deep learning has shown extraordinary performance in biomedical image analysis including various parasites diagnosis in the past few years. Here we summarize advances of deep learning in the field of protozoan parasites microscopic examination, focusing on publicly available microscopic image datasets of protozoan parasites. In the end, we summarize the challenges and future trends, which deep learning faces in protozoan parasite diagnosis.