Palmitic acid impairs human and mouse placental function by inhibiting trophoblast autophagy through induction of acyl-coenzyme A-binding protein (ACBP) upregulation.

STUDY QUESTION: Can exposure to palmitic acid (PA), a common saturated fatty acid, modulate autophagy in both human and mouse trophoblast cells through the regulation of acyl-coenzyme A-binding protein (ACBP)? SUMMARY ANSWER: PA exposure before and during pregnancy impairs placental development through mechanisms involving placental autophagy and ACBP expression. WHAT IS KNOWN ALREADY: High-fat diets, including PA, have been implicated in adverse effects on human placental and fetal development. Despite this recognition, the precise molecular mechanisms underlying these effects are not fully understood. STUDY DESIGN, SIZE, DURATION: Extravillous trophoblast (EVT) cell line HTR-8/SVneo and human trophoblast stem cell (hTSC)-derived EVT (hTSCs-EVT) were exposed to PA or vehicle control for 24 h. Female wild-type C57BL/6 mice were divided into PA and control groups (n = 10 per group) and subjected to a 12-week dietary intervention. Afterward, they were mated with male wild-type C57BL/6 mice and euthanized on Day 14 of gestation. Female ACBPflox/flox mice were also randomly assigned to control and PA-exposed groups (each with 10 mice), undergoing the same dietary intervention and mating with ACBPflox/floxELF5-Cre male mice, followed by euthanasia on Day 14 of gestation. The study assessed the effects of PA on mouse embryonic development and placental autophagy. Additionally, the role of ACBP in the pathogenesis of PA-induced placental toxicity was investigated. PARTICIPANTS/MATERIALS, SETTING, METHODS: The findings were validated using real-time PCR, Western blot, immunofluorescence, transmission electron microscopy, and shRNA knockdown approaches. MAIN RESULTS AND THE ROLE OF CHANCE: Exposure to PA-upregulated ACBP expression in both human HTR-8/SVneo cells and hTSCs-EVT, as well as in mouse placenta. PA exposure also induced autophagic dysfunction in HTR-8/SVneo cells, hTSCs-EVT, and mouse placenta. Through studies on ACBP placental conditional knockout mice and ACBP knockdown human trophoblast cells, it was revealed that reduced ACBP expression led to trophoblast malfunction and affected the expression of autophagy-related proteins LC3B-II and P62, thereby impacting embryonic development. Conversely, ACBP knockdown partially mitigated PA-induced impairment of placental trophoblast autophagy, observed both in vitro in human trophoblast cells and in vivo in mice. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Primary EVT cells from early pregnancy are fragile, limiting research use. Maintaining their viability is tough, affecting data reliability. The study lacks depth to explore PA diet cessation effects after 12 weeks. Without follow-up, understanding postdiet impacts on pregnancy stages is incomplete. Placental abnormalities linked to elevated PA diet in embryos lack confirmation due to absence of control groups. Clarifying if issues stem solely from PA exposure is difficult without proper controls. WIDER IMPLICATIONS OF THE FINDINGS: Consuming a high-fat diet before and during pregnancy may result in complications or challenges in successfully carrying the pregnancy to term. It suggests that such dietary habits can have detrimental effects on the health of both the mother and the developing fetus. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by the National Natural Science Foundation of China (82171664, 82301909) and the Natural Science Foundation of Chongqing Municipality of China (CSTB2022NS·CQ-LZX0062, cstc2019jcyj-msxmX0749, and cstc2021jcyj-msxmX0236). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

miR-181d-5p, which is upregulated in fetal growth restriction placentas, inhibits trophoblast fusion via CREBRF.

PURPOSE: Fetal growth restriction (FGR) is a common complication characterized by impaired placental function and unfavorable pregnancy outcomes. This study aims to elucidate the expression pattern of miR-181d-5p in FGR placentas and explore its effects on trophoblast fusion. METHODS: The expression pattern of miR-181d-5p in human FGR placentas were evaluated using qRT-PCR. Western blot, qRT-PCR, and Immunofluorescence analysis were performed in a Forskolin (FSK)-induced BeWo cell fusion model following the transfection of miR-181d-5p mimic or inhibitor. Potential target genes for miR-181d-5p were identified by screening miRNA databases. The interaction between miR-181d-5p and Luman/CREB3 Recruitment Factor (CREBRF) was determined through a luciferase assay. Moreover, the effect of CREBRF on BeWo cell fusion was examined under hypoxic conditions. RESULTS: Aberrant up-regulation of miR-181d-5p and altered expression of trophoblast fusion makers, including glial cell missing 1 (GCM1), Syncytin1 (Syn1), and E-cadherin (ECAD), were found in human FGR placentas. A down-regulation of miR-181d-5p expression was observed in the FSK-induced BeWo cell fusion model. Transfection of the miR-181d-5p mimic resulted in the inhibition of BeWo cell fusion, characterized by a down-regulation of GCM1 and Syn1, accompanied by an up-regulation of ECAD. Conversely, the miR-181d-5p inhibitor promoted BeWo cell fusion. Furthermore, miR-181d-5p exhibited negative regulation of CREBRF, which was significantly down-regulated in the hypoxia-induced BeWo cell model. The overexpression of CREBRF was effectively ameliorated the impaired BeWo cell fusion induced by hypoxia. CONCLUSIONS: Our study demonstrated that miR-181d-5p, which is elevated in FGR placenta, inhibited the BeWo cell fusion through negatively regulating the expression of CREBRF.

[Isolation and quantification of a 17-epi-dammarane triterpenoid rhuslactone from roots of Rhus chinensis and its preventive effects on coronary heart disease and thrombosis in zebrafish].

Based on mass spectrometry(MS)-guided separation strategy, compound 1 was obtained from the roots of Rhus chinensis. By comprehensive analysis of high resolution-electrospray ionization-mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR) data, and quantum chemical calculation of NMR(qcc-NMR) parameters, compound 1 was elucidated as rhuslactone, a 17-epi-dammarane triterpenoid with a rare 17α-side chain. An HPLC-ELSD method for its quantification in R. chinensis was established and adopted for the quantification of rhuslactone in different batches of R. chinensis. Rhuslactone displayed a good linear relationship within the range of 0.021 3-1.07 µmol·mL~(-1 )(r=0.997 6), and the average recovery was 99.34% [relative standard deviation(RSD) 2.9%). Moreover, the results of the evaluation test of the preventive effects of rhusalctone on coronary heart disease(CHD) and thrombosis showed that rhuslactone(0.11 nmol·mL~(-1)) significantly alleviated heart enlargement and venous congestion and increased cardiac output(CO), blood flow velocity(BFV), and heart rate, thereby reducing thrombus formation in zebrafish with CHD. The effects of rhuslactone on CO and BFV were superior to that of digoxin(1.02 nmol·mL~(-1)), and its effect on improving heart rate was comparable to that of digoxin. This study provides experimental references for the isolation, identification, quality control, and application of rhuslactone from R. chinensis against CHD. It is worth mentioning that this study has discussed some omissions in the determination of the stereochemistry of C-17 in dammarane triterpenoids in the present coursebook Chemistry of Chinese Medicine and some research papers, that is, the compound may be 17-epi-dammarane triterpenoid. This paper has also proposed steps for the establishment of C-17 stereochemistry.

MicroRNA cargo of extracellular vesicles released by skeletal muscle fibro-adipogenic progenitor cells is significantly altered with disuse atrophy and IL-1ß deficiency.

Fibro-adipogenic progenitor cells (FAPs) are a population of stem cells in skeletal muscle that play multiple roles in muscle repair and regeneration through their complex secretome; however, it is not well understood how the FAP secretome is altered with muscle disuse atrophy. Previous work suggests that the inflammatory cytokine IL-1ß is increased in FAPs with disuse and denervation. Inflammasome activation and IL-1ß secretion are also known to stimulate the release of extracellular vesicles (EVs). Here, we examined the microRNA (miRNA) cargo of FAP-derived, platelet-derived growth factor receptor A (PDGFRα+) EVs from hindlimb muscles of wild-type and IL-1ß KO mice after 14 days of single-hindlimb immobilization. Hindlimb muscles were isolated from mice following the immobilization period, and PDGFRα+ extracellular vesicles were isolated using size-exclusion chromatography and immunoprecipitation. Microarrays were performed to detect changes in miRNAs with unloading and IL-1ß deficiency. Results indicate that the PDGFRα+, FAP-derived EVs show a significant increase in miRNAs, such as miR-let-7c, miR-let-7b, miR-181a, and miR-124. These miRNAs have previously been demonstrated to play important roles in cellular senescence and muscle atrophy. Furthermore, the expression of these same miRNAs was not significantly altered in FAP-derived EVs isolated from the immobilized IL-1ß KO. These data suggest that disuse-related activation of IL-1ß can mediate the miRNA cargo of FAP-derived EVs, contributing directly to the release of senescence- and atrophy-related miRNAs. Therapies targeting FAPs in settings associated with muscle disuse atrophy may therefore have the potential to preserve muscle function and enhance muscle recovery.

A decrease in cluster of differentiation 2 expression on natural killer cells is associated with polycystic ovary syndrome but not influenced by metformin in a mouse model†.

PROBLEM: Natural killer (NK) cells from the peripheral blood and spleen represent the source from which various tissues replenish their immune cell populations. Hyperandrogenism and high interleukin-2 (IL-2) levels are factors present in polycystic ovary syndrome (PCOS). These factors and metformin, one of the commonest medications used in treating PCOS, may have an impact on NK cells. However, this is presently unknown. Here, we aimed to assess the distribution of peripheral blood and splenic NK cells and their CD2 and CD94 expression patterns in a PCOS mouse model and test whether metformin could reverse these effects. METHOD OF STUDY: Four mouse groups were designed as follows (n = 15/group): control, PCOS, PCOS plus vehicle, PCOS plus metformin. Dehydroepiandrosterone and a high-fat diet were administered to induce the PCOS mouse model. Flow cytometry was used to analyze the expressions of CD2 and CD94 on peripheral blood and splenic NK cells. RESULTS: PCOS mice had a low surface-density of CD2 on peripheral blood NK cells and a decreased percentage of CD2+ splenic NK cells. Metformin administration did not significantly influence these changes; however, it reduced the splenic NK cell counts. CONCLUSIONS: Our findings proved the association of PCOS with an altered expression of CD2 on peripheral blood and splenic NK cells and that of metformin with a lowered splenic NK cell reserve in PCOS conditions. These findings could further unlock key mechanisms in PCOS pathophysiology and in the mechanism of action of metformin, towards improving PCOS management.

[HADHA Inhibits the Migration and Invasion of HTR-8/SVneo Cells by Regulating PI3K/AKT Signaling Pathway].

Objective: To explore the effects of hydroxyacyl-CoA dehydrogenase alpha subunit (HADHA) on the migration and invasion of HTR-8/SVneo cells, a human trophoblast cell line, and its potential mechanism of action. Methods: Immunofluorescence staining was done to evaluate the expression levels of HADHA in samples of normal villi and recurrent spontaneous abortion (RSA) villi at 6-8 weeks. Lentiviral infection system was used to construct stable HTR-8/SVneo cell lines with HADHA overexpression and knockdown. Western blot, qRT-PCR, Wound-healing assay, and Transwell assay were used to determine the effect of HADHA on the migration and invasion of HTR-8/SVneo cells and the expression of relevant genes. Transcriptome sequencing and bioinformatics analysis were done to screen for the potential target genes and signaling pathways regulated by HADHA. The specific molecular mechanism of how HADHA regulates the migration and invasion of HTR-8/SVneo cells was examined by adding the inhibitor of protein kinase B (PKB/AKT). Results: HADHA was highly expressed in extravillous trophoblasts (EVT) of RSA villus samples as compared with samples from the normal control group. In HTR-8/SVneo cells overexpressing HADHA, the expression levels of migration and invasion-related genes, including HLA-G, MMP2, MMP9, and NCAD, were decreased (P<0.01,P<0.05), and the migration and invasion abilities of HTR-8/SVneo cells were weakened (P<0.05). HADHA knockdown increased the expression levels of HLA-G, MMP2, MMP9, and NCAD (P<0.01, P<0.05), and promoted the migration and invasion of HTR-8/SVneo cells (P<0.05). In addition, HADHA overexpression decreased the phosphorylation levels of PI3K and AKT (P<0.05) and inhibited the PI3K/AKT signaling pathway. HADHA knockdown activated the PI3K/AKT signaling pathway. When MK-2206, an AKT inhibitor, was added to stable HTR-8/SVneo cell lines with HADHA knockdown, the migration and invasion of the cells were significantly reduced. Conclusion: HADHA inhibits the migration and invasion of HTR-8/SVneo cells by inhibiting the PI3K/AKT signaling pathway.

Appropriate expression of P57kip2 drives trophoblast fusion via cell cycle arrest.

The syncytiotrophoblast, derived from cytotrophoblast fusion, is responsible for maternal-fetal exchanges, secretion of pregnancy-related hormones, and fetal defense against pathogens. Inadequate cytotrophoblast fusion can lead to pregnancy disorders, such as preeclampsia and fetal growth restriction. However, little is known about the mechanism of cytotrophoblast fusion in both physiological and pathological pregnancy conditions. In this study, P57kip2 (P57), a cell cycle-dependent kinase inhibitor that negatively regulates the cell cycle, was found to be up-regulated during the process of syncytialization in both primary trophoblast cells and BeWo cells. Co-immunofluorescence with proliferation markers Ki67 and Cyclin-CDK factors further showed that P57 specifically localizes in the post-mitotic cytotrophoblast subtype of the early pregnancy villi. Overexpression of P57 promoted trophoblast syncytialization by arresting the cell cycle at the G1/G0 phase and inhibiting proliferation. Blocking of the cell cycle through a serum starvation culture resulted in an enhancement of cytotrophoblast fusion and the up-regulation of P57. In both spontaneous cytotrophoblast fusion and forskolin-induced BeWo cell fusion models, an initial up-regulation of P57 was observed followed by a subsequent down-regulation. These findings indicate that proper expression of P57 at cytotrophoblast differentiation nodes plays an important role in trophoblast syncytialization.

An Improved Bluetooth Indoor Positioning Method Using Dynamic Fingerprint Window.

The weighted K-nearest neighbor algorithm (WKNN) is easily implemented, and it has been widely applied. In the large-scale positioning regions, using all fingerprint data in matching calculations would lead to high computation expenses, which is not conducive to real-time positioning. Due to signal instability, irrelevant fingerprints reduce the positioning accuracy when performing the matching calculation process. Therefore, selecting the appropriate fingerprint data from the database more quickly and accurately is an urgent problem for improving WKNN. This paper proposes an improved Bluetooth indoor positioning method using a dynamic fingerprint window (DFW-WKNN). The dynamic fingerprint window is a space range for local fingerprint data searching instead of universal searching, and it can be dynamically adjusted according to the indoor pedestrian movement and always covers the maximum possible range of the next positioning. This method was tested and evaluated in two typical scenarios, comparing two existing algorithms, the traditional WKNN and the improved WKNN based on local clustering (LC-WKNN). The experimental results show that the proposed DFW-WKNN algorithm enormously improved both the positioning accuracy and positioning efficiency, significantly, when the fingerprint data increased.

Anti-Cancer Effects of Emodin on HepG2 Cells as Revealed by 1H NMR Based Metabolic Profiling.

Hepatic carcinoma is one of the most common cancers in the world, with a high incidence. Emodin is an anthraquinone derived from Polygonum multiflorum Thunb, possessing anti-cancer activity. The purpose of this study is to investigate the anti-cancer effect of different dosages of emodin on HepG2 cells using a 1H NMR based metabolic approach complemented with qRT-PCR and flow cytometry to identify potential markers and discover the targets to explore the underlying mechanism. Emodin can dose-dependently inhibit the growth of HepG2 cells, perturb cell cycle progression, down-regulate the expression of genes and proteins related to glycolysis, and trigger intracellular ROS generation. Orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA) and correlation network analysis of the 1H NMR data showed significant changes in many endogenous metabolites after emodin exposure concerning oxidative stress and disturbances in amino acid and energy metabolism. These findings are helpful to understand the anti-cancer mechanism of emodin and provide a theoretical basis for its future application and development.

Clinical findings in 111 cases of influenza A (H7N9) virus infection.

BACKGROUND: During the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread among humans in China. Data were lacking on the clinical characteristics of the infections caused by this virus. METHODS: Using medical charts, we collected data on 111 patients with laboratory-confirmed avian-origin influenza A (H7N9) infection through May 10, 2013. RESULTS: Of the 111 patients we studied, 76.6% were admitted to an intensive care unit (ICU), and 27.0% died. The median age was 61 years, and 42.3% were 65 years of age or older; 31.5% were female. A total of 61.3% of the patients had at least one underlying medical condition. Fever and cough were the most common presenting symptoms. On admission, 108 patients (97.3%) had findings consistent with pneumonia. Bilateral ground-glass opacities and consolidation were the typical radiologic findings. Lymphocytopenia was observed in 88.3% of patients, and thrombocytopenia in 73.0%. Treatment with antiviral drugs was initiated in 108 patients (97.3%) at a median of 7 days after the onset of illness. The median times from the onset of illness and from the initiation of antiviral therapy to a negative viral test result on real-time reverse-transcriptase-polymerase-chain-reaction assay were 11 days (interquartile range, 9 to 16) and 6 days (interquartile range, 4 to 7), respectively. Multivariate analysis revealed that the presence of a coexisting medical condition was the only independent risk factor for the acute respiratory distress syndrome (ARDS) (odds ratio, 3.42; 95% confidence interval, 1.21 to 9.70; P=0.02). CONCLUSIONS: During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).

Spatial and temporal characteristics of insulator contaminations revealed by daily observations of equivalent salt deposit density.

The accurate estimation of deposits adhering on insulators is of great significance to prevent pollution flashovers which cause huge costs worldwide. Researchers have developed sensors using different technologies to monitor insulator contamination on a fine time scale. However, there is lack of analysis of these data to reveal spatial and temporal characteristics of insulator contamination, and as a result the scheduling of periodical maintenance of power facilities is highly dependent on personal experience. Owing to the deployment of novel sensors, daily Equivalent Salt Deposit Density (ESDD) observations of over two years were collected and analyzed for the first time. Results from 16 sites distributed in four regions of Hubei demonstrated that spatial heterogeneity can be seen at both the fine and coarse geographical scales, suggesting that current polluted area maps are necessary but are not sufficient conditions to guide the maintenance of power facilities. Both the local emission and the regional air pollution condition exert evident influences on deposit accumulation. A relationship between ESDD and PM10 was revealed by using regression analysis, proving that air pollution exerts influence on pollution accumulations on insulators. Moreover, the seasonality of ESDD was discovered for the first time by means of time series analysis, which could help engineers select appropriate times to clean the contamination. Besides, the trend component shows that the ESDD increases in a negative exponential fashion with the accumulation date (ESDD = a - b × exp(-time)) at a long time scale in real environments.

Enrichment and characterization of an anaerobic cellulolytic microbial consortium SQD-1.1 from mangrove soil.

Enrichment of microbial consortia provides an approach to simulate and investigate microbial communities in natural environments. In this study, a cellulolytic microbial consortium SQD-1.1 was enriched from mangrove soil of Qinglan port (Hainan, China) by 27 times continuous subcultivation under anaerobic static conditions. The consortium could completely degrade 0.2% (w/v) filter paper within 3 days and utilized it as the sole carbon source. PCR-denaturing gradient gel electrophoresis analysis revealed a stable microbial community structure in the incubation process of 10 days and in the procedure of subcultivation. Twenty-four operational taxonomic units belonging to seven phyla were obtained from the full-length 16S rRNA gene library. Five clones, closest related to the genera Alkaliflexus, Clostridium, Alistipes, Spirochaeta, and Trichococcus, were the predominant ones. Among them, M117, phylogeneticly showing high similarity (16S rRNA gene identity, 95.3%) with the cellulolytic anaerobic bacterium Clostridium straminisolvens CSK1(T), was the potential key cellulolytic bacterium. Using the plate cultivation method, 12 strains, including one potential new species and four potential new species of new genera, were isolated. The strain P2, corresponding to the most frequently detected clone (M05) in the 16S rRNA gene library, showed both CMCase and xylanase activity and may be another important cellulolytic bacterium. The findings of cellulase activity in cell pellet and cohesion and dockerin domains in metagenome data further suggested the potential of utilization of cellulosomes by the consortium to degrade cellulose. Consortium SQD-1.1 provides a candidate for investigating the mechanism of cellulose degradation under anoxic conditions in natural environments.

[CT and MRI findings in patients with autoimmune pancreatitis].

OBJECTIVE: To evaluate computed tomography (CT) and magnetic resonance imaging (MRI) findings in patients with autoimmune pancreatitis (AIP). METHODS: The imaging findings of pancreas and extra-pancreas in 24 patients with AIP were retrospectively reviewed. Among them, CT scan was performed in 18 patients, MRI in 11, and bGth CT and MRI in 10. RESULTS: The pancreas showed diffuse enlargement (25%, 6/24), focal enlargement (37. 5%, 9/24), combined enlargement (25%, 6/24) ,and no enlargement (12. 5%, 9/24). Unenhanced CT showed hypoattenuation in AIP area (n = 2) . After intravenous injection of contrast medium, 17 patients showed abnormal contrast enhancement in the affected pancreatic parenchyma, including hypoattenuation during the arterial phase (50%, 9/18) and hyper attenuation during the delayed phase (94. 4%, 17/18). Precontrast MRI showed abnormal signal intense (n =9), including hypointense on T1-weight images (T1 WI) (n = 7), hyperintense (n = 7) and hypointense (n = 2) on T2-weight images (TIWI). Enhanced MRI demonstrated abnormal contrast enhancement within lesions (n = 11), including hypoattenuation during the arterial phase (81. 8%, 9/11) and good enhancement during the delayed phase (100%, 11111). A capsule-like rim was seen around pancreas (37. 5%, 9/24), among which CT detected in 6 out of 18 patients and MRI found in 7 out of 11 patients.The main pancreatic duct lumen within lesions has no visualization (100%, 24/24) and upstream dilation of the main pancreatic duct (n = 8) , ranging from 2. 2 to 4. 5 mm(mean 3. 1 0. 47 mm) in diameter. Narrowing of the common bile duct was shown in 14 patients. Miscellaneous findings were: infiltration of extrapancreatic vein (n = 9) and artery (n = 1); mild fluid collection around pancreas (n = 2); pseudocysts (n = 3). Fourteen patients also presented one or more of the following extrapancreatic imaging findings: narrowing of the intra-hepatic bile duct or hilar duct (n = 5); thickening of gallbladder wall (n = 5); fibrosis in mesenteric (n = 2), in retroperitoneal (n = 2) and in ligamentum teres hepatis (n = 1); renal involvement (n = 3); peri-pancreatic or para-aortic lymphadenopathy (n = 10); and ulcerative colitis (n = 3). CONCLUSION: AIP display some characteristic CT and MRI imaging features: sausage-like change of the pancreas; capsule-like rims around lesions; delayed contrast enhancement in the affected pancreatic parenchyma; segment or diffuse pancreatic duct stenosis but mild upstream dilation and extrapancreatic organs involvement. CT and MRI findings combining with serological tests and pancreas biopsy can assist physicians to make accurate and timely diagnosis.

The utility of repeated computed tomography to track a foreign body penetrating the esophagus to the level of the thyroid gland.

OBJECTIVE: Foreign body (FB) ingestion is a common problem in otolaryngology. One uncommon complication of FB ingestion is penetration to the level of the thyroid gland. To our knowledge, only 21 such cases have been reported in the literature. Here, we report a case of an esophageal FB penetrating to the level of the right thyroid gland. CASE REPORT: The patient was a 38-year-old woman in whom an esophageal FB penetrated to the level of the right thyroid gland. We traced the path to the thyroid gland using repeated computed tomography (CT) scans and demonstrated the importance of multiplanar reconstruction in locating the FB and formulating a precise surgical plan. CONCLUSIONS: To our knowledge, this is the first report of repeat CT scans being used to demonstrate the migratory route, over time, of a FB penetrating through the esophagus to the level of the thyroid gland. Our results suggest that multiplanar reconstruction may play a key role in the precise diagnosis of a FB at the level of the thyroid gland and may help surgeons choose the best approach for removal.

A facile and on-site sensing strategy for phenolic compounds based on a novel nanozyme with high polyphenol oxidase-like activity.

Phenolic compounds (PCs) are diverse in nature and undergo complex migration and transformations in the environment, making it challenging to use techniques such as chromatography and other traditional methods to determine the concentration of PCs by separation, individual monitoring and subsequent addition. To address this issue, a facile and on-site strategy was developed to measure the concentration of PCs using a novel nanozyme with polyphenol oxidase-like activity. First, the nanozyme was designed by coordinating the asymmetric ligand nicotinic acid with copper to mimic the structure of mononuclear and trinuclear copper clusters of natural laccases. Subsequently, by introducing 2-mercaptonicotinic acid to regulate the valence state of copper, the composite nanozyme CuNA10S was obtained with significantly enhanced activity. Interestingly, CuNA10S was shown to have a broad substrate spectrum capable of catalyzing common PCs. Building upon the superior performance of this nanozyme, a method was developed to determine the concentration of PCs. To enable rapid on-site sensing, we designed and prepared CuNA10S-based test strips and developed a tailored smartphone sensing platform. Using paper strip sensors combined with a smartphone sensing platform with RGB streamlined the sensing process, facilitating rapid on-site analysis of PCs within a range of 0-100 µM. Our method offers a solution for the quick screening of phenolic wastewater at contaminated sites, allowing sensitive and quick monitoring of PCs without the need for standard samples. This significantly simplifies the monitoring procedure compared to more cumbersome large-scale instrumental methods.

Metabolic landscape and pathogenic insights: a comprehensive analysis of high ovarian response in infertile women undergoing in vitro fertilization.

BACKGROUND: In the realm of assisted reproduction, a subset of infertile patients demonstrates high ovarian response following controlled ovarian stimulation (COS), with approximately 29.7% facing the risk of Ovarian Hyperstimulation Syndrome (OHSS). Management of OHSS risk often necessitates embryo transfer cancellation, leading to delayed prospects of successful pregnancy and significant psychological distress. Regrettably, these patients have received limited research attention, particularly regarding their metabolic profile. In this study, we aim to utilize gas chromatography-mass spectrometry (GC-MS) to reveal these patients' unique serum metabolic profiles and provide insights into the disease's pathogenesis. METHODS: We categorized 145 infertile women into two main groups: the CON infertility group from tubal infertility patients and the Polycystic Ovary Syndrome (PCOS) infertility group. Within these groups, we further subdivided them into four categories: patients with normal ovarian response (CON-NOR group), patients with high ovarian response and at risk for OHSS (CON-HOR group) within the CON group, as well as patients with normal ovarian response (PCOS-NOR group) and patients with high ovarian response and at risk for OHSS (PCOS-HOR group) within the PCOS group. Serum metabolic profiles were analyzed using GC-MS. The risk criteria for OHSS were: the number of developing follicles > 20, peak Estradiol (E2) > 4000pg/mL, and Anti-Müllerian Hormone (AMH) levels > 4.5ng/mL. RESULTS: The serum metabolomics analysis revealed four different metabolites within the CON group and 14 within the PCOS group. Remarkably, 10-pentadecenoic acid emerged as a discernible risk metabolite for the CON-HOR, also found to be a differential metabolite between CON-NOR and PCOS groups. cysteine and 5-methoxytryptamine were also identified as risk metabolites for the PCOS-HOR. Furthermore, KEGG analysis unveiled significant enrichment of the aminoacyl-tRNA biosynthesis pathway among the metabolites differing between PCOS-NOR and PCOS-HOR. CONCLUSION: Our study highlights significant metabolite differences between patients with normal ovarian response and those with high ovarian response and at risk for OHSS within both the tubal infertility control group and PCOS infertility group. Importantly, we observe metabolic similarities between patients with PCOS and those with a high ovarian response but without PCOS, suggesting potential parallels in their underlying causes.

Study on the optimal time limit of frozen embryo transfer and the effect of a long-term frozen embryo on pregnancy outcome.

In this retrospective study conducted at Sichuan Jinxin Xinan Women and Children's Hospital spanning January 2015 to December 2021, our objective was to investigate the impact of embryo cryopreservation duration on outcomes in frozen embryo transfer. Participants, totaling 47,006 cycles, were classified into 3 groups based on cryopreservation duration: ≤1 year (Group 1), 1 to 6 years (Group 2), and ≥6 years (Group 3). Employing various statistical analyses, including 1-way ANOVA, Kruskal-Wallis test, chi-square test, and a generalized estimating equation model, we rigorously adjusted for confounding factors. Primary outcomes encompassed clinical pregnancy rate and Live Birth Rate (LBR), while secondary outcomes included biochemical pregnancy rate, multiple pregnancy rate, ectopic pregnancy rate, early and late miscarriage rates, preterm birth rate, neonatal birth weight, weeks at birth, and newborn sex. Patient distribution across cryopreservation duration groups was as follows: Group 1 (40,461 cycles), Group 2 (6337 cycles), and Group 3 (208 cycles). Postcontrolling for confounding factors, Group 1 exhibited a decreased likelihood of achieving biochemical pregnancy rate, clinical pregnancy rate, and LBR (OR < 1, aOR < 1, P < .05). Furthermore, an elevated incidence of ectopic pregnancy was observed (OR > 1, aOR > 1), notably significant after 6 years of freezing time [aOR = 4.141, 95% confidence intervals (1.013-16.921), P = .05]. Cryopreservation exceeding 1 year was associated with an increased risk of early miscarriage and preterm birth (OR > 1, aOR > 1). No statistically significant differences were observed in birth weight or sex between groups. However, male infant birth rates were consistently higher than those of female infants across all groups. In conclusion, favorable pregnancy outcomes align with embryo cryopreservation durations within 1 year, while freezing for more than 1 year may diminish clinical pregnancy and LBRs, concurrently elevating the risk of ectopic pregnancy and preterm birth.

A new metal ion chelator attenuates human tau accumulation-induced neurodegeneration and memory deficits in mice.

Neuronal neurofibrillary tangles containing Tau hyperphosphorylation proteins are a typical pathological marker of Alzheimer's disease (AD). The level of tangles in neurons correlates positively with severe dementia. However, how Tau induces cognitive dysfunction is still unknown, which leads to a lack of effective treatments for AD. Metal ions deposition occurs with tangles in AD brain autopsy. Reduced metal ion can improve the pathology of AD. To explore whether abnormally phosphorylated Tau causes metal ion deposition, we overexpressed human full-length Tau (hTau) in the hippocampal CA3 area of mice and primary cultured hippocampal neurons (CPHN) and found that Tau accumulation induced iron deposition and activated calcineurin (CaN), which dephosphorylates glycogen synthase kinase 3 beta (GSK3ß), mediating Tau hyperphosphorylation. Simultaneous activation of CaN dephosphorylates cyclic-AMP response binding protein (CREB), leading to synaptic deficits and memory impairment, as shown in our previous study; this seems to be a vicious cycle exacerbating tauopathy. In the current study, we developed a new metal ion chelator that displayed a significant inhibitory effect on Tau phosphorylation and memory impairment by chelating iron ions in vivo and in vitro. These findings provide new insight into the mechanism of memory impairment induced by Tau accumulation and develop a novel potential treatment for tauopathy in AD.