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Objectives: We aimed to evaluate the analytical performance of second-trimester maternal serum screening in China, and to compare if there are differences in sigma levels across different methods and months. Methods: A retrospective study was conducted to assess the analytical quality levels of laboratories by calculating the Sigma metrics with prenatal screening biomarkers: AFP, Total β-hCG, free β-hCG, uE3. Data from 591 laboratories were selected. Sigma metrics were computed using the formula: Sigma metrics(σ) = (%TEa - |%Bias|)/%CV. The Friedman test and Mann-Whitney test were used to compare differences across various methods and different months. The Hodges–Lehmann was used for determining 95 % confidence intervals of pseudo-medians. Results: Only uE3 showed significant monthly variations in sigma calculations. However, around 8 % of laboratories across all four analytes demonstrated sigma levels both above 6 and below 3 in different months. Laboratories utilizing time-resolved fluorescence methods significantly outperformed those using chemiluminescence in sigma level. For AFP, the pseudo-median difference between these methods lies within a 95 % confidence interval of (−3.22, −1.93), while for uE3, it is at (−2.30, −1.40). Notably, the median sigma levels for all analytes reached the 4-sigma threshold, with free β-hCG even attaining the 6-sigma level. Conclusion: With current standards, China's second-trimester maternal serum screening is of relatively high analytical quality, and variations in sigma levels exist across different months and methods.

Background: To investigate changes in the immunophenotypes of androgen receptor (AR), prostate-specific antigen (PSA), synaptophysin (Syn), chromogranin A (CgA), p53 and Ki-67 after neoadjuvant endocrine therapy (NET) for prostate cancer (PCa) and to analyze their clinical significance. Methods: Paired paraffin samples were collected from 40 PCa patients before and after NET, and immunohistochemistry were used to detect AR, PSA, Syn, CgA, p53 and Ki-67 expression. Based on The Cancer Genome Atlas (TCGA), Kaplan‒Meier survival curves were plotted for analysis of PSA and Ki-67 expression in relation to progression-free survival (PFS). Results: After NET, the mean scores for PSA and Ki-67 expression in PCa patients were lower than those before NET (P

Acrolein (ACR) is a ubiquitous environmental pollutant and byproduct of lipid peroxidation that has been implicated in male infertility. However, the molecular mechanisms underlying ACR-induced toxicity in Sertoli cells remain unclear. Given its role in inducing oxidative stress, we examined whether ferroptosis, an iron-dependent form of regulated cell death, could mediate ACR toxicity in Sertoli cells. We also tested if hydrogen sulfide (H2S), which has antioxidant and ACR detoxifying properties, could protect Sertoli cells from ACR-induced ferroptosis. ACR exposure decreased Sertoli cell viability, increased protein carbonylation and p38 MAPK phosphorylation, indicating oxidative injury. ACR also depleted glutathione (GSH), downregulated the cystine importer SLC7A11, increased intracellular ferrous iron (Fe2+) and lipid peroxidation, suggesting activation of ferroptosis. Consistently, the ferroptosis inhibitor deferoxamine (DFO) markedly attenuates ACR-induced cell death. Further studies revealed that ACR-induced ferroptotic changes were prevented by exogenous H2S and exaggerated by inhibition of endogenous H2S production. Furthermore, H2S also suppressed GPX4 inhibitor RSL3-induced intracellular ACR accumulation and ferroptosis. In summary, our study demonstrates that ACR induces ferroptotic cell death in Sertoli cells, which can be prevented by H2S through multiple mechanisms. Targeting the H2S pathway may represent a therapeutic strategy to mitigate ACR-induced Sertoli cell injury and preserve male fertility.

Abstract Background Extracellular vesicles (EVs) have been revealed to facilitate the development of oral squamous cavity cell carcinoma (OCSCC), while its supporting role in lymph node metastases is under continuous investigation. This study aimed to examine the function of cancer-associated fibroblasts (CAF)-derived EVs (CAF-EVs) during lymph node metastasis in OCSCC and the mechanisms. Methods CAF were isolated from OCSCC tissues of patients, and CAF-EVs were extracted and identified. EdU, colony formation, wound healing, and Transwell assays were performed. The OCSCC cells before and after CAF-EVs treatment were injected into mice to probe the effects of CAF-EVs on tumor growth and lymph node metastasis, respectively. The effect of CAF-EVs treatment on transcriptome changes in OCSCC cells was analyzed. Clinical data of patients with OCSCC were analyzed to determine the prognostic significance of the selected genes. Finally, loss-of-function assays were conducted to corroborate the involvement of polycomb complex protein BMI-1 (BMI1) and integrin beta1 (ITGB1). Results CAF-EVs promoted the malignant behavior of OCSCC cells and accelerated tumor growth and lymph node metastasis in mice. CAF-EVs significantly increased the expression of BMI1 and ITGB1, and the expression of BMI1 and ITGB1 was negatively correlated with the overall survival and relapse-free survival of OCSCC patients. Knockdown of BMI1 or ITGB1 in OCSCC cells abated the promoting effects of CAF-EVs in vitro and in vivo. Conclusion CAF-EVs elicited the metastasis-promoting properties in OCSCC by elevating BMI1 and ITGB1, suggesting that BMI1 and ITGB1 could be potential biomarkers and therapeutic targets for OCSCC.

Abstract TNF receptor-associated factors (TRAFs) are signaling adaptor proteins that play a crucial role in regulating cellular receptors’ signaling transduction to downstream pathways and exert multifaceted roles in regulating signaling pathways, cell survival, and carcinogenesis. The 13-cis-retinoic acid (RA), an active metabolite of vitamin A, exhibits anti-cancer properties, but the development of retinoic acid resistance poses a challenge in clinical application. This study aimed to investigate the relationship between TRAFs and retinoic acid sensitivity in various cancers. Here, we revealed that TRAFs’ expression varied significantly across The Cancer Genome Atlas (TCGA) cancer cohorts and human cancer cell lines. Additionally, inhibiting TRAF4, TRAF5, or TRAF6 improved retinoic acid sensitivity and reduced colony formation in ovarian cancer and melanoma cells. Mechanistically, knocking down TRAF4, TRAF5, or TRAF6 in retinoic acid-treated cancer cell lines increased the levels of procaspase 9 and induced cell apoptosis. Further in vivo studies using the SK-OV-3 and MeWo xenograft models confirmed the anti-tumor effects of TRAF knockdown combined with retinoic acid treatment. These findings support that combination therapy with retinoic acid and TRAF silencing may offer significant therapeutic advantages in treating melanoma and ovarian cancers.

Male infertility is a global concern, with a noticeable increase in the decline of spermatogenesis and sperm quality. However, there are limited clinically effective treatments available. This study aimed to investigate the potential effectiveness of puerarin in treating male infertility, which leads to gonadal changes. The results obtained from various analyses such as CASA, immunofluorescence, DIFF-Quick, hematoxylin and eosin (H&E), and periodic acid-Schiff (PAS) staining demonstrated that puerarin supplementation significantly alleviated the busulfan-induced reduction in spermatogenesis and sperm quality in both young and adult mice. Furthermore, puerarin exhibited a marked improvement in the damage caused by busulfan to the architecture of seminiferous tubules, causal epididymis, blood-testicular barrier (BTB), as well as spermatogonia and Sertoli cells. Similarly, puerarin significantly reduced the levels of total antioxidant capacity (T-AOC), malondialdehyde (MDA), and caspase-3 in the testes of busulfan-induced mice, as determined by microplate reader analysis. Additionally, RNA-seq data, RT-qPCR, and western blotting revealed that puerarin restored the abnormal gene expressions induced by busulfan to nearly healthy levels. Notably, puerarin significantly reversed the impact of busulfan on the expression of marker genes involved in spermatogenesis and oxidative stress. Moreover, puerarin suppressed the phosphorylation of p38, ERK1/2, and JNK in the testes, as observed through testicular analysis. Consequently, this study concludes that puerarin may serve as a potential alternative for treating busulfan-induced damage to male fertility by inactivating the testicular MAPK pathways. These findings may pave the way for the use of puerarin in addressing chemotherapy- or other factors-induced male infertility in humans.

PurposeTo explore the genotypes and allele frequencies of α, β and α+β thalassemias in Li minorities, which resided in Hainan Province of China for a long time.MethodsIn the present study, 1,438 newborns of the Li minority were collected from January 2020 to April 2021. The genotypes of thalassemia were detected by fluorescence PCR and verified by flow-through hybridization PCR analyses. Rare genotypes were detected by restriction fragment length polymorphism electrophoresis and Sanger DNA sequencing.ResultsAmong 1,438 participants, 1,024 (71.2%) were diagnosed with any kind of thalassemia. Among all thalassemia carriers, 902 (88.09%) subjects were diagnosed with α-thalassemia, and 18 subtypes of α-thalassemia were detected, with the top three genotypes being −α4.2/αα (25.39%), −α3.7/αα (22.62%) and αWSα/αα (16.96%). Thirty-two (3.13%) patients were β-thalassemia carriers, and 6 types of β-thalassemia genotypes were detected. The top two genotypes were βCD41–42/βN (46.88%) and β−28/βN (18.75%). Additionally, 90 (8.79%) cases were α + β-thalassemia, and the top two genotypes were −α3.7/αα, βCD41–42/βN (30.00%) and −α4.2/αα, βCD41–42/βN (26.67%). Furthermore, two genotypes (−α4.2/HKαα and βCD76 GCT > CCT/βN) were first identified in Hainan Province, and βCD76 GCT > CCT/βN was first identified in China.ConclusionNewborns of Li have a higher prevalence of thalassemia for a long period, and further education on the impact of thalassemia, follow-up studies of the clinical manifestation and treatment and proper intervention methods should be designed to reduce the burden of thalassemia and enhance the quality of life in Li newborns.

Abstract Real‐time monitoring of three‐dimensional stress in the field is an effective approach to detect evolving stress in roof rock and to evaluate rock bursts risk. However, the sensors or data transmission cables may be damaged due to the volatile environment found in coal mines, which can lead to the loss of relevant monitoring data, and some critical information for rock burst prediction may be missed entirely. A number of methods that use historical data to predict missing data or future structural states have been proposed. However, the performance of these methods is poor when the training data are insufficient owing to lack of data. To address this issue, a methodology framework is proposed to predict the mining‐induced stress when some monitoring data are missing. The framework uses a long short‐term memory neural network integrated with the transfer learning method. The proposed method can transfer the knowledge learned from complete monitored data of adjacent sensor to target sensor to boost forecasting. A case study has been conducted to evaluate the method. The results show that the developed model can significantly improve the prediction performance for the target domain, which can be improved further by increasing the size of the target domain training data available.

The study of the mechanical properties and failure behaviors for coal with different bedding structures at various medium strain rates is of great importance for revealing the mechanism of rock burst. In our study, we systematically analyze the uniaxial compressive strength (UCS), acoustic emission (AE) characteristics, failure pattern, and risk of rock burst on coal specimens with two bedding orientations under ranged in strain rates from 10−4 s−1 to 10−2 s−1. The results reflect that and the bedding direction and the strain rates significantly affect the UCS and failure modes of coal specimens. The UCS of coal specimens with loading directions perpendicular to bedding planes (horizontal bedding) increases logarithmically with increasing strain rate while the UCS increases first and then decreases of coal specimens with loading directions parallel to bedding planes (vertical bedding). The AE cumulative energy of the specimens with horizontal bedding is an order of magnitude higher than that of specimens with vertical bedding. However, it is independent of the strain rates. The energy release rates of these two types of bedded coal specimens increase in a power function as the strain rate increases. The coal specimens with horizontal bedding show violent failure followed by the ejection of fragments, indicating a high risk of rock burst. On the other hand, the coal specimens with vertical bedding exhibit a tensile splitting failure with a low risk of rock burst. Strain localization is a precursor of coal failure, and the concentration area of local principal strain is highly consistent with the initial damage area, and the area where the principal strain gradient is significantly increased corresponds to the fracture initiation area.

Roof rocks in coal mines are subjected to the combination of in situ stresses and dynamic stresses induced by mining activities. Understanding the mechanical properties of roof rocks under static and dynamic loads at medium strain rates is of great significance to revealing the mechanism of rock bursts. In this study, we employ the digital image correlation (DIC) technique to investigate the energy concentration and dissipation behaviors, failure mode, and deformation characteristics of roof rocks under combined static and dynamic loads. Our results show that both the static pre-stress and dynamic loading rate have significant effects on the uniaxial compressive strength of rock specimens. From the energy principle, when the static pre-stress is the same, both elastic strain energy density and dissipated energy density increase with increasing dynamic loading rate. The hazard of rock bursts increases with decreasing static pre-stress and increasing dynamic loading rate. At higher dynamic loading rates, more cracks are generated, and the failure becomes more violent. The crack initiation, propagation and coalescence processes are identified, and the failure mode is closely related to the evolution of the global principal strain field of the rock specimens.

A borehole deformation sensor for long-term stress monitoring in coal mine rock based on optical fiber Bragg gratings (FBGs) is presented. The sensor converts borehole deformation into optical fiber strain by using four rings. For each ring, two FBGs are bonded with the ring to measure the borehole deformation, and a reference FBG free from mechanical load is introduced to remove the temperature effect. Two simple checks on the test data can be performed to improve the test accuracy. Laboratory and field tests were conducted to validate the accuracy and long-term performance of the sensor. The results show that the sensor is capable of measuring stress in rock with good accuracy, and it performs well over a long period of time in coal mines. The developed sensor provides an approach for the long-term monitoring of stress changes in coal mine rock.

This paper investigates the finite-time leader-following consensus problem for multi-agent systems with switching topologies. First of all, consider the characteristic of failures, a failure distribution model which is more in line with the actual situation is established, and a semi-Markov chain is used to describe the topology switching of the multi-agent system, in which the transfer rate is time-varying. Secondly, based on the past state information, a topology-dependent consensus protocol is established, then the fault-tolerant consensus problem of leader-following multi-agent is transformed into the issue of system stability, according to the mode-dependent Lyapunov function and the finite time stochastic theorem, the sufficient conditions for the stability of the closed-loop system and the constraints of average residence time are obtained. In addition, an initial-state based $ {H_\infty } $ H ∞ performance index is proposed to reduce the influence of zero initial conditions on the system. Finally, a numerical example is provided to show the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

The incidence of Alzheimer's disease (AD) has been increasing in recent years as the world's population ages, which poses a significant challenge to public health. Due to the complexity of pathogenesis of AD, currently there is no effective treatment for it. In recent years, cell and gene therapy has attracted widespread attention in the treatment of neurodegenerative diseases. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) represent a novel cell-free therapy with numerous advantages over cell-based therapies owing to their low immunogenicity and high safety profile. We summarize recent progress in the application of EVs for treating AD and the specific mechanisms and outline the underlying mechanisms. We also explore various methods for optimizing the function of MSC-EVs, including gene editing, modifying stem cell culture conditions and peptide modification. In addition, we discuss the therapeutic potentials of MSC-EVs, as well as the obstacles that currently impede their clinical utilization. [ABSTRACT FROM AUTHOR]

A novel yttrium complex [Y(HIA)3(H2O)2]n·nYCl3 (HIA = isonicotinic acid) has been synthesized via a hydrothermal reaction and characterized by single crystal X-ray diffraction technique. The title complex features a one-dimensional (1-D) chain-like structure. A solid state photoluminescence measurement revealed that there is one strong emission peak at 487 nm. These peak can be assigned to the characteristic electronic transition and stacking effect inside the ligand. The title complex shows CIE (Commission Internationale de I' Éclairage) chromaticity coordinates in the blue region (0.1049, 0.1221). At the same time, the title complex has a wide band gap of 2.03 eV, which was revealed by a solid-state UV/Vis diffuse reflection experiment. [ABSTRACT FROM AUTHOR]

A novel up-conversion luminescence tetranuclear sodium complex [Na4(5-(carboxymethyl 2-oxo-propyl) amino isophthalic acid)(H2O)9] is synthesized by a solvothermal reaction, and its crystal structure is determined by single-crystal X-ray diffraction. The title complex crystallizes as a triclinic system with the P 1 ¯ space group and exists as an isolated tetranuclear complex. Numerous intermolecular hydrogen bonds and van der waals forces form a three-dimensional supramolecular network. Solid-state diffuse reflectance data show that there is a wide optical band gap of 2.91 eV. The solid-state photoluminescence spectrum reveals that the complex shows an up-conversion emission in the blue region of the light spectrum. Time-dependent density functional theory calculations reveal that this emission can be attributed to ligand-to-ligand charge transfer. [ABSTRACT FROM AUTHOR]