Nur77 improves ovarian function in reproductive aging mice by activating mitophagy and inhibiting apoptosis.

Reproductive aging not only affects the fertility and physical and mental health of women but also accelerates the aging process of other organs. There is an urgent need newfor novel mechanisms, targets, and drugs to break the vicious cycle of mitochondrial dysfunction, redox imbalance, and germ cell apoptosis associated with ovarian aging. Autophagy, recognized as a longevity mechanism, has recently become a focal point in anti-aging research. Although mitophagy is a type of autophagy, its role and regulatory mechanisms in ovarian aging, particularly in age-related ovarian function decline, remain unclear. Nerve growth factor inducible gene B (Nur77) is an early response gene that can be stimulated by oxidative stress, DNA damage, metabolism, and inflammation. Recent evidence recommends that decreased expression of Nur77 is associated with age-related myocardial fibrosis, renal dysfunction, and Parkinson's disease; however, its association with ovarian aging has not been studied yet. We herein identified Nur77 as a regulator of germ cell senescence, apoptosis, and mitophagy and found that overexpression of Nur77 can activate mitophagy, improve oxidative stress, reduce apoptosis, and ultimately enhance ovarian reserve in aged mice ovaries. Furthermore, we discovered an association between Nur77 and the AKT pathway through String and molecular docking analyses. Experimental confirmation revealed that the AKT/mTOR signaling pathway is involved in the regulation of Nur77 in ovarian function. In conclusion, our results suggest Nur77 as a promising target for preventing and treating ovarian function decline related to reproductive aging.

Analysis of Fertility Prognosis and Risk Factors in Patients Post-Gestational Trophoblastic Disease.

To retrospectively analyze the fertility outcomes and prognosis of gestational trophoblastic disease (GTD) patients, providing a basis for targeted fertility guidance and counseling. 82 GTD patients of childbearing age who received treatment at the Obstetrics and Gynecology Department of Lanzhou University First Hospital from January 2016 to January 2023 were stratified into re-pregnancy (n = 20) and non-re-pregnancy (n = 33) cohorts based on their pregnancy outcomes. The impacts of various factors on pregnancy outcomes were subsequently evaluated, encompassing the rates of subsequent pregnancies, live births, miscarriages, ectopic pregnancies, and ongoing pregnancies. Finally, logistics regression model was employed to analyze the risk factors affecting re-pregnancy in GTD patients. The study delineated those patients with different GTD pathologies had varying re-pregnancy rates (mole, erosive mole and choriocarcinoma accounted for 66.04%, 30.19% and 3.77%, respectively). Treatment predominantly involved uterine curettage, with fewer cases receiving chemotherapy alone or in conjunction with curettage accounted for 67.92%, 5.66%, and 26.42%, respectively. The average chemotherapy frequency was 4.59 ± 2.43 sessions, and a majority sought reproductive counseling. Re-pregnancy occurred in 37.74% of patients. The live birth rate was 65.00%, with miscarriage and ectopic pregnancy rates at 25.00% and 5.00% respectively. Logistic regression analysis pinpointed the absence of pre-pregnancy counseling as a significant independent risk factor for re-pregnancy in GTD patients (p < 0.05). While chemotherapy may influence ovarian function, with the majority of patients desiring children post-recovery, pregnancy rates remain high. Fertility counseling significantly enhances re-pregnancy success rates in GTD survivors, emphasizing its recommendation for those aiming to conceive post-recovery.

Hydrogel Loaded with Extracellular Vesicles: An Emerging Strategy for Wound Healing.

An increasing number of novel biomaterials have been applied in wound healing therapy. Creating beneficial environments and containing various bioactive molecules, hydrogel- and extracellular vesicle (EV)-based therapies have respectively emerged as effective approaches for wound healing. Moreover, the synergistic combination of these two components demonstrates more favorable outcomes in both chronic and acute wound healing. This review provides a comprehensive discussion and summary of the combined application of EVs and hydrogels to address the intricate scenario of wounds. The wound healing process and related biological mechanisms are outlined in the first section. Subsequently, the utilization of EV-loaded hydrogels during the wound healing process is evaluated and discussed. The moist environment created by hydrogels is conducive to wound tissue regeneration. Additionally, the continuous and controlled release of EVs from various origins could be achieved by hydrogel encapsulation. Finally, recent in vitro and in vivo studies reported on hydrogel dressings loaded with EVs are summarized and challenges and opportunities for the future clinical application of this therapeutic approach are outlined.

Hot water mobilizes the metabolism of energy, soluble sugar, cell wall, and phenolics to cope with chilling injury in postharvest snap beans.

BACKGROUND: Snap beans (Phaseoulus vulgaris L.) are very sensitive to low temperature during postharvest storage. Pitting, rusting, and water-soaked patches are typical chilling injury (CI) symptoms of snap beans. The appearance of these symptoms reduces the storage quality of snap beans. The energy, soluble carbohydrates, cell wall, and phenolic metabolisms of refrigerated snap beans and their relationship to CI treated with 35 °C hot water (HW) were investigated. RESULTS: HW treatment reduced CI index and electrolyte leakage and increased the contents of soluble solids, titratable acidity, and chlorophyll. HW treatment maintained higher activities of proton ATPase, calcium ATPase, and cytochrome c oxidase, which resulted in the accumulation of more adenosine triphosphate, adenosine diphosphate, and energy charge. The accumulation of soluble sugar induced by HW treatment was correlated with the stimulation of sucrose phosphate synthase and sucrose synthase. The prevention effect of HW treatment on the degradation of cell wall components was related to the inhibition of pectin methylesterase and cellulase. HW-induced phenol accumulation is associated with an increase in shikimate dehydrogenase, phenylalanine ammonia lyase, cinnamate-4-hydroxylase, and 4-coumarine-coenzyme A ligase, as well as a decrease in polyphenol oxidase. CONCLUSION: The alleviating effect of HW on CI is due to its regulation of energy, soluble sugar, cell wall, and phenolic metabolism. Therefore, HW treatment may be an effective means to reduce CI of snap beans. © 2024 Society of Chemical Industry.

Molecular-level periodic arrays of long-chain poly(3-hexylthiophene-2,5-diyl) driven by an electric field.

Two-dimensional (2D) periodic arrays of conductive polymers represent attractive platforms for wiring functional molecules into the integrated circuits of molecular electronics. However, the large-scale assembly of polymer periodic arrays at the molecular level faces challenges such as curling, twisting, and aggregation. Here, we assembled the periodic arrays of long-chain poly(3-hexylthiophene-2,5-diyl) (P3HT, Mw = 65 k) at the solid-liquid interface by applying an electric field, within which the charged chain segments were aligned. Atomic force microscopy (AFM) imaging revealed that individual P3HT chains assemble into monolayers featuring face-on orientation, extended chain conformation and isolated packing, which is thermodynamically more stable than folded chains in 2D polycrystals. The assembly process is initiated with the formation of disordered clusters and progresses through voltage-dependent nucleation and growth of extended-chain arrays, wherein continuous conformational adjustments along the nucleation pathway exhibit dependence on the cluster size.

Dexamethasone Long-Term Controlled Release from Injectable Dual-Network Hydrogels with Porous Microspheres Immunomodulation Promotes Bone Regeneration.

Long-lasting, controlled-release, and minimally invasive injectable platforms that provide a stable blood concentration to promote bone regeneration are less well developed. Using hexagonal mesoporous silica (HMS) loaded with dexamethasone (DEX) and poly(lactic-co-glycolic acid) (PLGA), we prepared porous DEX/HMS/PLGA microspheres (PDHP). In contrast to HMS/PLGA microspheres (HP), porous HMS/PLGA microspheres (PHP), DEX/PLGA microspheres (DP), and DEX/HMS/PLGA microspheres (DHP), PDHP showed notable immuno-coordinated osteogenic capabilities and were best at promoting bone mesenchymal stem cell proliferation and osteogenic differentiation. PDHP were combined with methacrylated silk (SilMA) and sodium alginate (SA) to form an injectable photocurable dual-network hydrogel platform that could continuously release the drug for more than 4 months. By adjusting the content of the microspheres in the hydrogel, a zero-order release hydrogel platform was obtained in vitro for 48 days. When the microsphere content was 1%, the hydrogel platform exhibited the best biocompatibility and osteogenic effects. The expression levels of the osteogenic gene alkaline phosphatases, BMP-2 and OPN were 10 to 15 times higher in the 1% group than in the 0% group, respectively. In addition, the 1% microsphere hydrogel strongly stimulated macrophage polarization to the M2 phenotype, establishing an immunological milieu that supports bone regrowth. The aforementioned outcomes were also observed in vivo. The most successful method for correcting cranial bone abnormalities in SD rats was to use a hydrogel called SilMA/SA containing 1% drug-loaded porous microspheres (PDHP/SS). The angiogenic and osteogenic effects of this treatment were also noticeably greater in the PDHP/SS group than in the control and blank groups. In addition, PDHP/SS polarized M2 macrophages and suppressed M1 macrophages in vivo, which reduced the local immune-inflammatory response, promoted angiogenesis, and cooperatively aided in situ bone healing. This work highlights the potential application of an advanced hydrogel platform for long-term, on-demand, controlled release for bone tissue engineering.

Synthesis of azelaic acid copolyester plasticizers and their application in PVC.

A series of 2-methyl-1,3-propanediol (MPO) modified azelaic acid and hexylene glycol copolyester (PHMAZ) plasticizers with varying contents were synthesized using a direct esterification melt polycondensation method, and their structures were characterized systematically. Analysis using infrared spectroscopy and nuclear magnetic resonance spectroscopy confirmed the synthesis of the designed copolyester structure. Gel permeation chromatography (GPC) tests indicated that the number average molecular weight of each copolyester sample ranged between 2000 and 3000. These copolyesters were used to plasticize polyvinyl chloride (PVC) resin, and the glass transition temperature of the plasticized PVC samples was tested using a differential scanning calorimeter (DSC). Further characterization of the plasticizing effects was conducted using an electronic universal testing machine. The research results showed that as the content of MPO increased, the plasticizing effect of the copolyester initially increased and then decreased. Specifically, the copolyester containing 45% MPO, PHMAZ-45, demonstrated the best plasticizing effect on PVC, with the glass transition temperature of the plasticized PVC system around -35 °C, elongation at break at 908.4%, and a plasticizing efficiency of 254.5%. Additionally, this new type of copolyester plasticizer uses bio-based raw materials, exhibits excellent plasticizing effects, and the preparation process is stable and controllable. It holds promising potential to replace traditional volatile and toxic phthalate esters, presenting significant industrial application value.

PDTC improves cognitive impairment in LPS-induced ARDS by regulating miR-181c/NF-κB axis-mediated neuroinflammation.

BACKGROUND: Cognitive impairment is a severe complication of acute respiratory distress syndrome (ARDS). Emerging studies have revealed the effects of pyrrolidine dithiocarbamate (PDTC) on improving surgery-induced cognitive impairment. The major aim of the study was to investigate whether PDTC protected against ARDS-induced cognitive dysfunction and to identify the underlying mechanisms involved. METHODS: The rat model of ARDS was established by intratracheal instillation of lipopolysaccharide (LPS), followed by treatment with PDTC. The cognitive function of rats was analyzed by the Morris Water Maze, and pro-inflammatory cytokines were assessed by quantitative real-time PCR, enzyme-linked immunosorbent assay, and western blot assays. A dual-luciferase reporter gene assay was performed to identify the relationship between miR-181c and its target gene, TAK1 binding protein 2 (TAB2). RESULTS: The results showed that PDTC improved cognitive impairment and alleviated neuroinflammation in the hippocampus in LPS-induced ARDS model. Furthermore, we demonstrated that miR-181c expression was downregulated in the hippocampus of the ARDS rats, which was restored by PDTC treatment. In vitro studies showed that miR-181c alleviated LPS-induced pro-inflammatory response by inhibiting TAB2, a critical molecule in the nuclear factor (NF)-κB signaling pathway. CONCLUSION: PDTC improves cognitive impairment in LPS-induced ARDS by regulating miR-181c/NF-κB axis-mediated neuroinflammation, providing a potential opportunity for the treatment of this disease.

Design and synthesis of matrine derivatives for anti myocardial ischemia-reperfusion injury by promoting angiogenesis.

Myocardial ischemia/reperfusion (MI/R) is a common cardiovascular disease that seriously affects the quality of life and prognosis of patients. In recent years, matrine has attracted widespread attention in the treatment of cardiovascular diseases. This study designed, synthesized, and characterized 20 new matrine derivatives and studied their protective effects on ischemia-reperfusion injury through in vivo and in vitro experiments. Based on cellular assays, most newly synthesized derivatives have a certain protective effect on Hypoxia/Reoxygenation (H/R) induced H9C2 cell damage, with compound 22 having the best activity and effectively reducing cell apoptosis and necrosis. In vitro experimental data shows that compound 22 can significantly reduce the infarct size of rat myocardium and improve cardiac function after MI/R injury. In summary, compound 22 is a new potential cardioprotective agent that can promote angiogenesis and enhance antioxidant activity by activating ADCY5, CREB3l4, and VEGFA, thereby protecting myocardial cell apoptosis and necrosis induced by MI/R.

Prognostication of colorectal cancer liver metastasis by CE-based radiomics and machine learning.

The liver is the most common organ for the formation of colorectal cancer metastasis. Non-invasive prognostication of colorectal cancer liver metastasis (CRLM) may better inform clinicians for decision-making. Contrast-enhanced computed tomography images of 180 CRLM cases were included in the final analyses. Radiomics features, including shape, first-order, wavelet, and texture, were extracted with Pyradiomics, followed by feature engineering by penalized Cox regression. Radiomics signatures were constructed for disease-free survival (DFS) by both elastic net (EN) and random survival forest (RSF) algorithms. The prognostic potential of the radiomics signatures was demonstrated by Kaplan-Meier curves and multivariate Cox regression. 11 radiomics features were selected for prognostic modelling for the EN algorithm, with 835 features for the RSF algorithm. Survival heatmap indicates a negative correlation between EN or RSF risk scores and DFS. Radiomics signature by EN algorithm successfully separates DFS of high-risk and low-risk cases in the training dataset (log-rank test: p < 0.01, hazard ratio: 1.45 (1.07-1.96), p < 0.01) and test dataset (hazard ratio: 1.89 (1.17-3.04), p < 0.05). RSF algorithm shows a better prognostic implication potential for DFS in the training dataset (log-rank test: p < 0.001, hazard ratio: 2.54 (1.80-3.61), p < 0.0001) and test dataset (log-rank test: p < 0.05, hazard ratio: 1.84 (1.15-2.96), p < 0.05). Radiomics features have the potential for the prediction of DFS in CRLM cases.

Screening, expression and anti-tumor functional identification of anti-LAG-3 nanobodies.

OBJECTIVE: To screen and obtain specific anti-lymphocyte activation gene-3 (LAG3) nanobody sequences, purify and express recombinant anti-LAG3 nanobody, and verify its effect on promoting T cells to kill tumor cells. METHODS: Based on the camel derived natural nanobody phage display library constructed by the research group, the biotinylated LAG3 antigen was used as the target, and the anti-LAG3 nanobody sequences were screened by biotin-streptavidin liquid phase screening, phage-ELISA and sequencing. The sequence-conjµgated human IgG1 Fc fragment was obtained, the recombinant anti-LAG3 nanobody expression vector was constructed, the expression of the recombinant anti-LAG3 nanobody was induced by IPTG and purified, and the characteristics and functions of the recombinant anti-LAG3 nanobody were verified by SDS-PAGE, Western blot, cytotoxicity assay, etc. RESULTS: One anti-LAG3 nanobody sequence was successfully screened, and the corresponding recombinant anti-LAG3 nanobody-expressing bacteria were constructed. The results of SDS-PAGE, Western blot and cytotoxicity assay showed that the recombinant anti-LAG3 nanobody was successfully expressed, which was specific, and it could promote the killing ability of T cells against tumor cells, and the optimal concentration was 200 µg/mL. CONCLUSION: The recombinant anti-LAG3 nanobody screened and expressed has specific and auxiliary anti-tumor cell effects, which lays a foundation for its subsequent application.

Chinese herbal medicine and acupuncture for insomnia in stroke patients: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Insomnia is highly prevalent in stroke patients; however, there is no ideal intervention. This systematic review examined the effect and safety of Chinese herbal medicine (CHM) and acupuncture on sleep in adults with stroke. METHODS: Six databases were searched from inception to June 2023 to identify randomised controlled trials (RCTs). The primary outcome was Pittsburgh Sleep Quality Index (PSQI) scores. Risk of bias and evidence quality was assessed. A pairwise random-effect meta-analysis was performed. RESULTS: A total of 54 RCTs published in 55 articles were finally included in the systematic review, including 35 of CHM and 19 of acupuncture therapies. Compared with placebo/sham procedure, CHM and acupuncture were more effective in improving PSQI scores. The evidence of moderate quality suggested that CHM outperformed benzodiazepine drugs (BZDs) while it presented an effect similar to that of non-BZDs in improving sleep quality. CHM and acupuncture also provided additional benefits to the patients treated with pharmacological agents alone. However, the evidence specific to individual CHM prescriptions lay in various factors and methodological quality, and the evidence on the comparative effectiveness between acupuncture and other therapies was conflicting or limited. CONCLUSIONS: Overall, CHM and acupuncture used alone or in combination with pharmacotherapy can safely improve sleep in stroke patients with insomnia. In the future, RCTs on outstanding CHM prescriptions and the comparative effectiveness research between acupuncture and other therapies are needed. REGISTRATION: PROSPERO No. CRD42020194029 and No. CRD42020194030.

Tannic acid crosslinked chitosan/gelatin/SiO2 biopolymer film with superhydrophobic, antioxidant and UV resistance properties for prematuring fruit packaging.

The environmental pollution caused by plastic films urgently requires the development of non-toxic, biodegradable, and renewable biopolymer films. However, the poor waterproof and UV resistance properties of biopolymer films have limited their application in fruit packaging. In this work, a novel tannic acid cross-linked chitosan/gelatin film with hydrophobic silica coating (CGTS) was prepared. Relying on the adhesion of tannic acid and gelatin to silica, the coating endows CGTS film with excellent superhydrophobic properties. Especially, the contact angle reaches a maximum value 152.6°. Meanwhile, tannic acid enhanced the mechanical strength (about 36.1 %) through the forming of hydrogen bonding and the network structure. The prepared CGTS films showed almost zero transmittance to ultraviolet light and exhibited excellent radical scavenging ability (∼76.5 %, DPPH). Hence, CGTS film is suitable as a novel multifunctional packaging material for the agriculture to protect premature fruits, or the food industry used in environments exposed to ultraviolet radiation and rainwater.

Cell-Membrane-Coated Metal-Organic Framework Nanocarrier Combining Chemodynamic Therapy for the Inhibition of Hepatocellular Carcinoma Proliferation.

Chemodynamic therapy (CDT) employs hydrogen peroxide (H2O2) within the tumor microenvironment (TME) to initiate the Fenton reaction and catalyze the generation of hydroxyl radicals (·OH) for targeted therapy. Metal ion-based nanomaterials have garnered significant attention as catalysts due to their potent anti-tumor effects. Hypoxia in the TME is often associated with cancer cell development and metastasis, with HIF-1α being a pivotal factor in hypoxia adaptation. In this study, an organic framework called MIL-101 (Fe) was designed and synthesized to facilitate H2O2-induced ·OH production while also serving as a carrier for the HIF-1α inhibitor Acriflavine (ACF). A biomimetic nanomedical drug delivery system named MIL-101/ACF@CCM was constructed by encapsulating liver cancer cell membranes onto the framework. This delivery system utilized the homologous targeting of tumor cell membranes to transport ACF, inhibiting HIF-1α expression, alleviating tumor hypoxia, and catalyzing ·OH production for effective tumor eradication. Both in vivo and in vitro experiments confirmed that combining ACF with chemotherapy achieved remarkable tumor inhibition by enhancing ROS production and suppressing HIF-1α expression.

Characterization of chitosan film incorporated pine bark extract and application in carp slices packaging.

Active films based on chitosan incorporated with pine bark extract (PBE) were prepared and characterized. Subsequently, these films were utilized for packaging carp slices in refrigerated storage at 4 ± 1 °C. Analysis of the physicochemical properties and biological activity of the active films revealed that, except for water content, all assessed indices showed an increasing trend with an increase in the amount of supplemental PBE. As this trend progresses, scanning electron microscopy (SEM) analysis revealed deposition on the film surface accompanied by transverse lines and fractures, while the color of the film gradually changed from light yellow to reddish-brown. Fourier transform infrared spectroscopy (FTIR) indicated that the phenolic hydroxyl groups in PBE interacted with the hydrogen in the amino groups of chitosan molecules to form non-covalent bonds. X-ray diffraction analysis (XRD) showed that the reaction between PBE and chitosan altered the crystalline structure of chitosan molecules. Moreover, the analysis of the effects of active films on the pH, water-holding capacity, thiobarbituric acid values, and the total bacterial counts of carp slices revealed that in terms of preservation, films containing 30 % PBE were the most effective, using which the shelf life of carp slices could be extended by 50 %.

Iron-based materials functionalized with carbon and phosphorus recovered from sludge enhanced the formation of stable minerals to passivate lead and chromium in wastewater and soil.

The bioaccumulation and toxicity of heavy metals are serious threats to human activities and ecological health. The exploitation of environmentally friendly passivated materials is major importance for the remediation of heavy metal contaminated soil. This research developed a new type of environmental functional material with a core-shell structure, which is an iron-based material functionalized with phosphorus and carbon from sludge for heavy metal pollution remediation. The results indicated that the C/P@Fe exhibits excellent heavy metal removal ability, and the maximum removal rates of the two heavy metals in simulated wastewater could reach 100% under optimum reaction conditions. It also effectively converts the labile Cr/Pb into the stable fraction after 28 days of incubation, which increased the maximum residual fraction percentage of Cr and Pb by 32.43% and 160% in soil. Further analysis found that the carbon layer wrapped around the iron base could improve the electron transport efficiency of reducing iron, phosphorus and ferrum could react with heavy metal ions to form stable minerals, such as FeCr2O4, FeO·Cr2O3, Pb5(PO4)3OH, PbCO3, 2PbCO3·Pb(OH)2 and PbS, after reacting with C/P@Fe. The study demonstrated that the Iron-based materials functionalized with carbon and phosphorus from sludge provided a more efficient way to remove heavy metals.

Genome-wide identification of GH28 family and insight into its contributions to pod shattering resistance in Brassica napus L.

Rapeseed (Brassica napus L.), accounts for nearly 16% of vegetable oil, is the world's second produced oilseed. However, pod shattering has caused significant yield loses in rapeseed production, particularly during mechanical harvesting. The GH28 genes can promote pod shattering by changing the structure of the pod cell wall in Arabidopsis. However, the role of the GH28 gene family in rapeseed was largely unknown. Therefore, a genome-wide comprehensive analysis was conducted to classify the role of GH28 gene family on rapeseed pod shattering. A total of 37 BnaGH28 genes in the rapeseed genome were identified. These BnaGH28s can be divided into five groups (Group A-E), based on phylogenetic and synteny analysis. Protein property, gene structure, conserved motif, cis-acting element, and gene expression profile of BnaGH28 genes in the same group were similar. Specially, the expression level of genes in group A-D was gradually decreased, but increased in group E with the development of silique. Among eleven higher expressed genes in group E, two BnaGH28 genes (BnaA07T0199500ZS and BnaC06T0206500ZS) were significantly regulated by IAA or GA treatment. And the significant effects of BnaA07T0199500ZS variation on pod shattering resistance were also demonstrated in present study. These results could open a new window for insight into the role of BnaGH28 genes on pod shattering resistance in rapeseed.

Mandarin-speaking Children With Cochlear Implants Face Challenges in Using F0 Expansion to Express Contrastive Focus.

OBJECTIVES: Children with cochlear implants (CIs) face challenges in perceiving fundamental frequency (F0) information because CIs do not transmit F0 effectively. In Mandarin, F0 can contrast meanings at the word level, that is, via lexical tones with distinct F0 contours, and signal contrastive relations between words at the utterance-level, that is, via contrastive focus with expanded F0 range and longer duration. Mandarin-speaking children with CIs have been reported to face challenges in producing distinct F0 contours across tones, but early implantation facilitates tonal acquisition. However, it is still unclear if utterance-level prosody, such as contrastive focus, is also challenging for these children, and if early implantation also offers benefits for focus production. Therefore, this study asked how accurately children with CIs can produce contrastive focus, and if early implantation leads to more accurate focus production, with acoustic patterns approaching that of children with typical hearing (TH). DESIGN: Participants included 55 Mandarin-speaking children (3 to 7 years) with CIs and 55 age-matched children with TH. Children produced noun phrases with and without contrastive focus, such as RED-COLORED cat versus red-colored cat. Three adult native listeners perceptually scored the productions as correct or incorrect. The "correct" productions were then acoustically analyzed in terms of F0 range and duration. RESULTS: Based on the perceptual scores, children with CIs produced focus with significantly lower accuracy (38%) than their TH peers (84%). The acoustic analysis on their "correct" productions showed that children with TH used both F0 and duration to mark focus, producing focal syllables with an expanded F0 range and long duration, and postfocal syllables with a reduced F0 range and short duration. However, children with CIs differed from children with TH in that they produced focal syllables with long duration but not an expanded F0 range, although they produced postfocal syllables with a reduced F0 range and short duration like their TH peers. In addition, early implantation correlated with the percept of more accurate focus productions and better use of F0 range in focal marking. CONCLUSIONS: This study finds that Mandarin-speaking children with CIs are still learning to apply appropriate acoustic cues to contrastive focus. The challenge appears to lie in the use of an expanded F0 range to mark focus, probably related to the limited transmission of F0 information through the CI devices. These findings thus have implications for parents and those working with children with CIs, showing that utterance-level prosody also requires speech remediation, and underscores the critical role of identifying problems early in the acquisition of F0 functions in Mandarin, not only at the word level but also at the utterance-level.

Differential mRNA and lncRNA Expression Profiles Associated with Early Pregnancy Loss in ART Patients.

Early pregnancy loss (EPL) is the most common complication in assisted reproductive technology (ART). However, the precise causes for nearly 50% patients remain unexplained. In the current study, we aimed to discover the differentially expressed profiling of mRNAs and lncRNAs by RNA sequencing (RNA-seq). Human chorionic villi tissues were collected from patients with EPL and natural control (NC) group. RNA sequencing (RNA-seq) of these specimens was performed for transcriptome analysis. As a result, we identified a total of 141 mRNAs and 137 lncRNAs that were significantly differentially expressed between villi tissues from EPL and NC. Functional enrichment analyses indicated enrichment of differentially expressed genes involved in pathways were associated with growth hormone receptor binding, PI3K-Akt signaling pathway, Jak-STAT signaling pathway, transcriptional misregulation in cancer, metabolic pathways and Rap1 signaling pathway. Additionally, the co-expression networks (lncRNA-miRNA-mRNA) was constructed based on the correlation analysis between the differentially expressed RNAs.7 mRNAs and 6 lncRNAs were successfully technically validated with RT-PCR. In conclusion, our results suggest a direction for the further study of EPL-related mRNAs and lncRNAs and may ultimately assist in understanding the pathogenesis of EPL.