Growth differentiation factor 11 regulates high glucose-induced cardiomyocyte pyroptosis and diabetic cardiomyopathy by inhibiting inflammasome activation.

BACKGROUND: Diabetic cardiomyopathy (DCM) is a crucial complication of long-term chronic diabetes that can lead to myocardial hypertrophy, myocardial fibrosis, and heart failure. There is increasing evidence that DCM is associated with pyroptosis, a form of inflammation-related programmed cell death. Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor ß superfamily, which regulates oxidative stress, inflammation, and cell survival to mitigate myocardial hypertrophy, myocardial infarction, and vascular injury. However, the role of GDF11 in regulating pyroptosis in DCM remains to be elucidated. This research aims to investigate the role of GDF11 in regulating pyroptosis in DCM and the related mechanism. METHODS AND RESULTS: Mice were injected with streptozotocin (STZ) to induce a diabetes model. H9c2 cardiomyocytes were cultured in high glucose (50 mM) to establish an in vitro model of diabetes. C57BL/6J mice were preinjected with adeno-associated virus 9 (AAV9) intravenously via the tail vein to specifically overexpress myocardial GDF11. GDF11 attenuated pyroptosis in H9c2 cardiomyocytes after high-glucose treatment. In diabetic mice, GDF11 alleviated cardiomyocyte pyroptosis, reduced myocardial fibrosis, and improved cardiac function. Mechanistically, GDF11 inhibited pyroptosis by preventing inflammasome activation. GDF11 achieved this by specifically binding to apoptosis-associated speck-like protein containing a CARD (ASC) and preventing the assembly and activation of the inflammasome. Additionally, the expression of GDF11 during pyroptosis was regulated by peroxisome proliferator-activated receptor α (PPARα). CONCLUSION: These findings demonstrate that GDF11 can treat diabetic cardiomyopathy by alleviating pyroptosis and reveal the role of the PPARα-GDF11-ASC pathway in DCM, providing ideas for new strategies for cardioprotection.

The radiomics features of the temporal lobe region related to menopause based on MR-T2WI can be used as potential biomarkers for AD.

Menopause may be an important pathogenic factor for Alzheimer's disease (AD). The M1 polarization of microglia and neuroinflammatory responses occur in the early pathogenetic stages of AD. Currently, no effective monitoring markers are available for AD's early pathological manifestations. Radiomics is an automated feature generation method for the extraction of hundreds of quantitative phenotypes (radiomics features) from radiology images. In this study, we retrospectively analyzed the magnetic resonance T2-weighted imaging (MR-T2WI) on the temporal lobe region and clinical data of both premenopausal and postmenopausal women. There were three significant differences were identified for select radiomic features in the temporal lobe between premenopausal and postmenopausal women, i.e. the texture feature Original-glcm-Idn (OI) based on the Original image, the filter-based first-order feature Log-firstorder-Mean (LM), and the texture feature Wavelet-LHH-glrlm-Run Length Nonuniformity (WLR). In humans, these three features were significantly correlated with the timing of menopause. In mice, these features were also different between the sham and ovariectomy (OVX) groups and were significantly associated with neuronal damage, microglial M1 polarization, neuroinflammation, and cognitive decline in the OVX groups. In AD patients, OI was significantly associated with cognitive decline, while LM was associated with anxiety and depression. OI and WLR could distinguish AD from healthy controls. In conclusion, radiomics features based on brain MR-T2WI scans have the potential to serve as biomarkers for AD and noninvasive monitoring of pathological progression in the temporal lobe of the brain in women undergoing menopause.

Variations in mitochondrial DNA coding and D-loop region are associated with early embryonic development defects in infertile women.

Mitochondrial DNA (mtDNA) plays a critical role in oocyte maturation, fertilization, and early embryonic development. Defects in mtDNA may determine the alteration of the mitochondrial function, affecting cellular oxidative phosphorylation and ATP supply, leading to impaired oocyte maturation, abnormal fertilization, and low embryonic developmental potential, ultimately leading to female infertility. This case-control study was established to investigate the correlation between mtDNA variations and early embryonic development defects. Peripheral blood was collected for next-generation sequencing from women who suffered the repeated failures of in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) cycles due to early embryonic development defects as well as in-house healthy controls, and the sequencing results were statistically analyzed for all subjects. This study found that infertile women with early embryonic development defects carried more mtDNA variants, especially in the D-loop region, ATP6 gene, and CYTB gene. By univariate logistic regression analysis, 16 mtDNA variants were associated with an increased risk of early embryonic development defects (OR > 1, p < 0.05). Furthermore, we identified 16 potentially pathogenic mtDNA variants only in infertile cases. The data proved that mtDNA variations were associated with early embryonic development defects in infertile Chinese women.

Supraphysiologic doses of 17ß-estradiol aggravate depression-like behaviors in ovariectomized mice possibly via regulating microglial responses and brain glycerophospholipid metabolism.

BACKGROUND: 17ß-Estradiol (E2) is generally considered neuroprotective in humans. However, the current clinical use of estrogen replacement therapy (ERT) is based on the physiological dose of E2 to treat menopausal syndrome and has limited therapeutic efficacy. The efficacy and potential toxicity of superphysiological doses of ERT for menopausal neurodegeneration are unknown. METHODS: In this study, we investigated the effect of E2 with a supraphysiologic dose (0.5 mg/kg, sE2) on the treatment of menopausal mouse models established by ovariectomy. We performed the open field, Y-maze spontaneous alternation, forced swim tests, and sucrose preference test to investigate behavioral alterations. Subsequently, the status of microglia and neurons was detected by immunohistochemistry, HE staining, and Nissl staining, respectively. Real-time PCR was used to detect neuroinflammatory cytokines in the hippocampus and cerebral cortex. Using mass spectrometry proteomics platform and LC-MS/ MS-based metabolomics platform, proteins and metabolites in brain tissues were extracted and analyzed. BV2 and HT22 cell lines and primary neurons and microglia were used to explore the underlying molecular mechanisms in vitro. RESULTS: sE2 aggravated depression-like behavior in ovariectomized mice, caused microglia response, and increased proinflammatory cytokines in the cerebral cortex and hippocampus, as well as neuronal damage and glycerophospholipid metabolism imbalance. Subsequently, we demonstrated that sE2 induced the pro-inflammatory phenotype of microglia through ERα/NF-κB signaling pathway and downregulated the expression of cannabinoid receptor 1 in neuronal cells, which were important in the pathogenesis of depression. CONCLUSION: These data suggest that sE2 may be nonhelpful or even detrimental to menopause-related depression, at least partly, by regulating microglial responses and glycerophospholipid metabolism.

Comparative analysis of the vaginal microbiome of healthy and polycystic ovary syndrome women: a large cross-sectional study.

RESEARCH QUESTION: What are the different features of the vaginal microbiome (VMB) between patients with polycystic ovary syndrome (PCOS) and healthy women? DESIGN: A cross-sectional study was conducted at a single academic university-affiliated centre. A total of 1446 participants were recruited (PCOS group, n =713, control group, n = 733). Vaginal swabs were analysed using 16S rRNA gene sequencing. The diversity and composition of the microbiome were compared between the PCOS group and the control group. Microbial interaction networks and functional prediction were investigated. RESULTS: The PCOS group had a higher alpha diversity than the control group (Shannon P = 0.03, Simpson P = 0.02), and higher intra-group variability was observed in PCOS group (P < 2.2E-16). At the genus level, the proportion of Lactobacillus decreased (85.1% versus 89.3%, false discovery rate [FDR] = 0.02), whereas the proportion of Gardnerella vaginalis and Ureaplasma increased in the PCOS group (5.1% versus 3.3%, FDR = 0.006; 1.2% versus 0.6%, FDR = 0.002, respectively). Lactobacillus acidophilus, Prevotella buccalis and G. vaginalis were identified as the main differential species. L. acidophilus was positively correlated with serum levels of anti-Müllerian hormone (AMH), and triglyceride (P = 2.01E-05, P = 0.004, respectively). P. buccalis was negatively correlated with serum levels of AMH and testosterone (P = 0.002, P = 0.003, respectively). G. vaginalis was positively correlated with serum levels of AMH, oestradiol and progesterone (P = 0.004, P = 0.005, P = 0.03, respectively). The VMB interaction network indicated that Lactobacillus crispus, Prevotella timonensis, and P. buccalis could be key drivers in the PCOS group. Overall, 55 predicted genes were found to be differentially abundant between PCOS and the control (FDRs < 0.25). CONCLUSIONS: The PCOS group had a higher diversity of vaginal microbiome and showed an enhanced level of heterogeneity. The proportion of Lactobacillus in the PCOS group decreased, whereas the proportions of Gardnerella and Ureaplasma increased. These results warrant further research that can validate the correlation between PCOS and VMB.

Mutation analysis of tubulin beta 8 class VIII in infertile females with oocyte or embryonic defects.

Variants of tubulin beta 8 class VIII (TUBB8) have been shown to be associated with female infertility characterized by oocyte or embryonic defects. To further investigate the mutational spectrum of TUBB8 and the prevalence of variants, we performed Sanger sequencing of TUBB8 on a total of 115 infertile females who had undergone repeated in vitro fertilization cycles with oocyte or embryonic defects and 200 healthy controls. A total of 31 variants which were absent from the controls were identified in 36 unrelated individuals, accounting for a large proportion of this cohort (31.3%). All of the variants including heterozygous/homozygous missense variants and a heterozygous frameshift insertion variant were at conserved sites and predicted to be deleterious. Besides, these variants had diverse phenotypic effects, including not only oocyte maturation arrest, fertilization failure, and early embryonic arrest, but also multi-pronuclei (MPN) formation, which is a new phenotype associated with TUBB8 variants. Overall, this study reveals a large number of variants of the TUBB8 gene in infertile females with oocyte or embryonic defects. Our results not only broaden the mutational and phenotypic spectra of TUBB8 variants, but also further confirm the critical role of TUBB8 in oocyte maturation, fertilization, and early embryonic development.

Increased risk of metabolic dysfunction in children conceived by assisted reproductive technology.

AIMS/HYPOTHESIS: Assisted reproductive technology (ART) is the most widely used treatment for infertility and has resulted in millions of births worldwide. The safety of the offspring has been of the utmost concern. Previous studies suggested an increase in metabolic disorders in offspring later in life. The aim of the present study was to investigate metabolic changes at age 6-10 years in offspring conceived as a result of in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI). METHODS: A total of 380 children born from IVF/ICSI and a matched control group of 380 naturally conceived children, all aged 6-10 years, were recruited. Anthropometric measures, ultrasound and serum tests were performed for body mass, glucose metabolism and lipid profiles, and examination of vasculature structure. RESULTS: The children conceived by ART showed significantly higher fasting blood glucose and serum insulin levels and HOMA-IR (adjusted ß [95% CI]: fasting blood glucose 0.49 [0.42, 0.55]; loge-transformed insulin 0.28 [0.20, 0.35]; loge-transformed HOMA-IR 0.38 [0.30, 0.46]), as well as a lower HOMA-B and serum apolipoprotein A (ApoA) levels (adjusted ß [95% CI]: loge-transformed HOMA-B -0.19 [-0.27, -0.11]; ApoA -0.17 [-0.21, -0.13]), when compared with the control group. Furthermore, the ultrasound scan indicated elevated carotid intima-media thickness in children conceived by ART (ß 0.13 [95% CI 0.12, 0.13]). CONCLUSIONS/INTERPRETATION: Children conceived by IVF/ICSI have a less favourable glucose and cardiovascular metabolic profile in childhood when compared with naturally conceived children. The underlying mechanisms and potential long-term consequences need to be elucidated in future studies. Graphical abstract.

A genome-wide association study identifies FSHR rs2300441 associated with follicle-stimulating hormone levels.

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) play critical roles in female reproduction, while the underlying genetic basis is poorly understood. Genome-wide association studies (GWASs) of FSH and LH levels were conducted in 2590 Chinese females including 1882 polycystic ovary syndrome (PCOS) cases and 708 controls. GWAS for FSH level identified multiple variants at FSHR showing genome-wide significance with the top variant (rs2300441) located in the intron of FSHR. The A allele of rs2300441 led to a reduced level of FSH in the PCOS group (ß = -.43, P = 6.70 × 10-14 ) as well as in the control group (ß = -.35, P = 6.52 × 10-4 ). In the combined sample, this association was enhanced after adjusting for the PCOS status (before: ß = -.38, P = 1.77 × 10-13 ; after: ß = -.42, P = 3.33 × 10-16 ), suggesting the genetic effect is independent of the PCOS status. The rs2300441 explained sevenfold higher proportion of the FSH variance than the total variance explained by the two previously reported FSHR missense variants (rs2300441 R2 = 1.40% vs rs6166 R2 = 0.17%, rs6165 R2 = 0.03%). GWAS for LH did not identify any genome-wide significant associations. In conclusion, we identified genome-wide significant association between variants in FSHR and circulating FSH first, with the top associated variant rs2300441 might be a primary contributor at the population level.

Variation analysis of tousled like kinase 1 gene in patients with sporadic premature ovarian insufficiency.

Tousled like kinase 1 (TLK1), a member of DNA repair family, participates in the regulation of chromatin assembly and is associated with early menopause and premature ovarian insufficiency (POI) in European women. However, whether the sequence variant in the TLK1 gene was causative for POI is still elusive. Here we performed direct sequencing of the TLK1 gene in 192 patients with sporadic POI. All exons and exon-intron boundaries of TLK1 were amplified and sequenced. Six known single-nucleotide polymorphisms were identified in POI, including rs149844334, rs11553951, rs757600673, rs2277339, rs113416007 and rs17283147. No novel variant was identified, which indicates that sequence variants in the coding region of TLK1 might be uncommon in Chinese women with POI. The role of TLK1 in POI pathogenesis needs to be further explored in larger cohorts from Chinese and other ethnic populations.

Variation analysis of SOX8 gene in Chinese men with non-obstructive azoospermia or oligozoospermia.

Sox8, encoding a SRY-related HMG box transcription factor, is essential in Sertoli cells for germ cell differentiation via regulation of integrity of the blood-testis barrier (BTB) as well as Sertoli-germ cell adhesion. Inactivation of Sox8 gene in mice causes postnatal progressive spermatogenic failure, resulting in male infertility. This study aims to investigate whether variants of SOX8 contribute to pathogenesis of idiopathic non-obstructive azoospermia (NOA) or oligozoospermia. A case-control genetic study was conducted in which all exons and exon-intron boundaries of SOX8 gene were screened in 190 NOA and 139 oligozoospermia cases by Sanger sequencing. The detected variants were examined in 284 normospermic controls. Nine known single-nucleotide polymorphisms (SNPs) of SOX8 gene were identified, and four of them exist simultaneously in oligo/azoospermia patients. A comparison of allele/genotype frequencies of these variants showed no significant difference between oligo/azoospermia cases and controls. The results indicate that deleterious variants in SOX8 gene may not be a common cause for oligo/azoospermia in Chinese men. Considering ethnic diversity, SOX8 could not be ruled out as a candidate gene for male infertility. The role of SOX8-mediated Sertoli cell function and BTB integrity played in the pathogenesis of male infertility needs to be further explored in other populations.

Dennd1a, a susceptibility gene for polycystic ovary syndrome, is essential for mouse embryogenesis.

BACKGROUND: The DENND1A has been identified as a guanine nucleotide exchange factor for small GTPase Rab35, which functions in endocytic trafficking to mediate the recycling of selective cargos. Genetic alterations within the DENND1A gene have been implicated in human disease such as polycystic ovary syndrome (PCOS). However, the role of DENND1A in developmental and reproductive processes is largely unknown. RESULTS: Using Dennd1a gene knockout mice, we uncovered that homogeneous Dennd1a-/- mutants died around embryonic day (E) 14.5. The brain of Dennd1a-/- embryos exhibited defects, partially attributed to the dysregulation of cell division and survival in the telencephalon. The transcription of Fgf8 mRNA was ectopically elevated in the dorsal midline of telencephalon, concomitant with a decrease of active ß-catenin and Axin2 in the brain of Dennd1a-/- embryos. During liver morphogenesis, the ablation of Dennd1a impaired hepatic cell proliferation, the differentiation of hepatocyte, and hepatic hematopoiesis. In addition, loss of Dennd1a also affected the development of primordial germ cells. CONCLUSIONS: We demonstrate that Dennd1a, a susceptibility gene for PCOS, is essential for embryogenesis, probably through the mediation of endocytic recycling of selective cargos that are involved in cell signaling crucial for the development of multiple embryonic organ systems.

[Ecological benefits of Gastrodia elata-Phallus impudicus sequential planting pattern].

Gastrodia elata is a kind of precious traditional Chinese medicine. In the process of cultivation of G. elata, due to the influence of continuous cropping obstacles and other factors, the fungus materials and land that have been planted with G. elata are often abandoned, resulting in a great waste of resources. Based on the planting characteristics of G. elata and Phallus impudicus and the previous research experience in ecological agriculture, this paper analyzed the ecological adaptability characteristics of G. elata and P. impudicus, and summarized the key techniques of the G. elata-P. impudicus sequential planting pattern. Keeping track of the planting area, fungus-growing materials consumption and market sales of G. elata-P. impudicus sequential planting pattern, the ecological benefits of G. elata-P. impudicus sequential planting pattern from the aspects of utilization rate of fungus-growing materials were analyzed, the value of land resources per unit area, ecological environmental protection, labor cost and economic benefits were consi-dered. The technical principle of G. elata-P. impudicus sequential planting pattern was expounded according to their ecological habit, the season of harvest and planting, the difference of composition of fungus-growing materials, and the microbial ecology. The sequential planting pattern of G. elata-P. impudicus not only realized the double production of medicinal materials and edible fungi, reduced the waste of old fungus-growing materials, but also transformed the energy from nutrition-supplied fungi to edible and medicinal fungi, which guaranteed the ecological recycling and utilization of G. elata in the process of cultivation.

Direct Nanomachining on Semiconductor Wafer By Scanning Electrochemical Microscopy.

Scanning electrochemical microscopy (SECM) is one of the most important instrumental methods of modern electrochemistry due to its high spatial and temporal resolution. We introduced SECM into nanomachining by feeding the electrochemical modulations of the tip electrode back to the positioning system, and we demonstrated that SECM is a versatile nanomachining technique on semiconductor wafers using electrochemically induced chemical etching. The removal profile was correlated to the applied tip current when the tip was held stationary and when it was moving slowly (<20 µm s-1 ), and it followed Faraday's law. Both regular and irregular nanopatterns were translated into a spatially distributed current by the homemade digitally controlled SECM instrument. The desired nanopatterns were "sculpted" directly on a semiconductor wafer by SECM direct-writing mode. The machining accuracy was controlled to the sub-micrometer and even nanometer scales. This advance is expected to play an important role in electrochemical nanomachining for 3D micro/nanostructures in the semiconductor industry.

Research of laser-induced damage of aluminum alloy 5083 on micro-arc oxidation and composite coatings treatment.

The laser-induced damage of aluminum alloy 5083 is affected by its surface treatment. Here, we investigate the effects of aluminum alloy's ability of laser-induced damage on micro-arc oxidation and composite coatings treatment. Results demonstrate a distinct difference of damage parameters on laser pulse duration at 355 nm between micro-arc oxidation and composite coatings treatment on aluminum alloy, including the laser-induced damage threshold, particulate pollutants for different surface treatment, and the damage morphology, respectively. We now find that the threshold of laser-induced damage is improved a lot through simulative calculation and experiments. Furthermore, the experimental results suggests that surface treatment contribute to the number of particulate pollutants and the microstructure of damaged pit.

Mutational analysis of IZUMO1R in women with fertilization failure and polyspermy after in vitro fertilization.

PURPOSE: The etiology of fertilization failure and polyspermy during assisted reproductive technology (ART) remains elusive. The aim of this study was to determine whether mutations in the IZUMO1 receptor (IZUMO1R) gene, which is essential for mammalian fertilization, contribute to the pathogenesis of fertilization failure or polyspermy in humans. METHODS: We recruited 215 female subjects with fertilization failure/poor fertilization, 330 females with polyspermy, and 300 matched controls. All subjects underwent IVF treatment. Peripheral blood DNA of cases was extracted and screened for mutations in IZUMO1R gene. RESULTS: Four rare single nucleotide polymorphisms (SNPs) of the IZUMO1R were identified among specimens from patients with fertilization failure and polyspermy but were absent in the 300 control subjects. These included a missense SNP (rs76779571 in exon 4), which was found in two fertilization failure patients, and a nonsynonymous SNP (rs61742524 in exon 1) and two synonymous SNPs (rs76781645 in exon 1 and rs377369966 in intron 2), which were found among three polyspermy cases. CONCLUSIONS: The variations in IZUMO1R might play a role in the pathogenesis of fertilization failure and polyspermy, and the putative functions and effects of these rare variants require further studies.

[Antagonistic effect of curcumin on lipid peroxidation of rats poisoned by paraquat].

OBJECTIVE: To explore the pathogenesis of paraquat poisoning and observe the change in lipid peroxidation of rats treated with different doses of curcumin. METHODS: A total of 50 8-week-old male Wistar rats (clean grade) were randomly divided into high-dose curcumin plus conventional treatment group, low-dose curcumin plus conventional treatment group, high-dose curcumin treatment group, poisoned group, and blank control group. Glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) levels in rat serum were measured at 1, 3, 7, 14, and 21 d post paraquat injection. RESULTS: Compared with the blank control group, other groups had significantly higher MDA levels but lower SOD, GSH-PX, and CAT activities. The high-dose, low-dose curcumin plus conventional treatment, and high-dose curcumin treatment groups had significantly lower serum lipid peroxidation levels compared with the poisoned group and among them the high-dose curcumin plus conventional treatment group had the most significant improvement. CONCLUSION: Curcumin can significantly decrease serum lipid peroxidation level in rats and inhibit and delay the occurrence and progression of the damage to the body.

[Inhibitory effects of curcumin on inflammatory cytokines in rats with paraquat poisoning].

OBJECTIVE: To explore the mechanism of paraquat (PQ) poisoning and to observe the changes in inflammatory cytokines in PQ-exposed rats treated in different ways. METHODS: Fifty 8-week-old clean male Wistar rats were randomly divided into high-dose curcumin plus conventional treatment group, low-dose curcumin plus conventional treatment group, high-dose curcumin group, PQ poisoning group, and blank control group. On days 1, 3, 5, 7, 14, and 21 after PQ exposure, serum levels of transforming growth factor-ß1(TGF-ß1) , tumor necrosis factor-α (TNF-α) , and interleukin-6 (IL-6) were measured. The pathological changes in lung tissue were evaluated by HE staining. RESULTS: Compared with the blank control group, the high-dose curcumin plus conventional treatment group, low-dose curcumin plus conventional treatment group, high-dose curcumin group, and PQ poisoning group had significantly increased serum levels of TGF-ß1, TNF-α, and IL-6 (P<0.05) , and the three cytokines in each group reached peak levels on day 14 after exposure. Compared with the PQ poisoning group, the high-dose curcumin group had significantly reduced serum levels of TGF-ß1, TNF-α, and IL-6 (P<0.05). On day 21 after exposure, there were no significant differences in serum levels of TGF-ß1, TNF-α, and IL-6 between the high-dose curcumin plus conventional treatment group and the low-dose curcumin plus conventional treatment group (P>0.05). The HE staining revealed alveolar inflammatory changes on days 1~7 and massive pulmonary fibrosis on days 14~21 in the high-dose curcumin plus conventional treatment group, low-dose curcumin plus conventional treatment group, high-dose curcumin group, and PQ poisoning group, but the above changes were milder in the high-dose curcumin group than in the PQ poisoning group. CONCLUSION: For rats with PQ poisoning, curcumin can significantly reduce inflammatory response and pathological changes in lung tissue and inhibit and delay the development and progression of body injury.

Oligoasthenospermia is correlated with increased preeclampsia incidence in subfertile couples undergoing in vitro fertilization and embryo transfer: a secondary analysis of a randomized clinical trial.

OBJECTIVE: To evaluate whether intergroup differences in the risk of maternal pregnancy complications after in vitro fertilization (IVF) vary with male factor. DESIGN: A post hoc exploratory secondary analysis of data from a multicenter, randomized, controlled noninferiority trial (NCT03118141). SETTING: Academic fertility centers. PATIENT(S): A total of 1,131 subfertile women with complete recording of their male partner's semen parameters during the trial were enrolled. All participants underwent intracytoplasmic sperm injection followed by frozen embryo transfer (ET) as part of their assisted reproductive technology treatment protocol. INTERVENTION(S): Women were divided into the oligoasthenospermia (n = 405) and normospermia (n = 726) groups according to the quality of male sperm. MAIN OUTCOME MEASURE(S): Pregnancy complications, principally including the incidence of preeclampsia. RESULT(S): Notably, we found that the risk of maternal preeclampsia was significantly higher in the oligoasthenospermia group than in the normospermia group. After adjustments for confounding factors by multivariate logistic regression analysis, the incidence of preeclampsia in the oligoasthenospermia group was still significantly higher than that in the normospermia group (6.55% vs. 3.60%; odds ratio, 0.529; 95% confidence interval, 0.282-0.992). However, there were no significant differences in terms of embryo quality, cumulative live birth rate, other pregnancy complications, or neonatal outcomes between the 2 groups. CONCLUSION(S): Oligoasthenospermia was associated with a higher risk of maternal preeclampsia in subfertile couples undergoing IVF-ET treatment. In clinical practice, it is essential to thoroughly evaluate the sperm quality and quantity of male partners before IVF-ET. Further research is needed to establish the causal relationships between semen quality and adverse pregnancy complications, particularly preeclampsia, and explore potential interventions.

NVP-BHG712 alleviates ovariectomy-induced osteoporosis by modulating osteoclastogenesis.

Postmenopausal osteoporosis (PMOP) is closely related to the pathogenesis of osteoclasts, with the Cathepsin K (CTSK) protein playing a crucial role. Our study aimed to screen small molecule compounds targeting CTSK and evaluate their impact on PMOP. Through molecular docking, we identified NVP-BHG712 as significantly inhibiting osteoclast differentiation and bone resorption. NVP-BHG712 also effectively suppressed CTSK activity and exhibited strong binding affinity to CTSK protein. Furthermore, NVP-BHG712 regulated the expression of inflammatory factors and modulated the balance between M1 and M2 macrophage polarization. In the mouse model of ovariectomy-induced osteoporosis, NVP-BHG712 rescued bone loss by inhibiting excessive osteoclast activation. These findings suggest that NVP-BHG712 may be a promising treatment for pathological osteoporosis by alleviating osteoclast function.

A leveling method based on current feedback mode of scanning electrochemical microscopy.

Substrate leveling is an essential but neglected instrumental technique of scanning electrochemical microscopy (SECM). In this technical note, we provide an effective substrate leveling method based on the current feedback mode of SECM. By using an air-bearing rotary stage as the supporter of an electrolytic cell, the current feedback presents a periodic waveform signal, which can be used to characterize the levelness of the substrate. Tuning the adjusting screws of the tilt stage, substrate leveling can be completed in minutes by observing the decreased current amplitude. The obtained high-quality SECM feedback curves and images prove that this leveling technique is valuable in not only SECM studies but also electrochemical machining.