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Abstract Objective To investigate the effects of different drug treatments on uterine artery blood flow parameters, serum placental growth factor (PLGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and sFlt-1/PLGF in patients with recurrent spontaneous abortion and to explore the predictive value of uterine artery blood flow parameters, serum PLGF, sFlt-1, and sFlt-1/PLGF for pregnancy outcomes. Methods This retrospective cohort study included 173 patients who experienced recurrent spontaneous abortion and 100 control patients. Patients with recurrent spontaneous abortion were divided into an aspirin group (75 patients), aspirin combined with low molecular weight heparin (LMWH) group (68 patients), and non-drug group (30 patients) based on different drug treatments. Uterine artery blood flow parameters at gestational weeks 30-31+6 were monitored for the four groups, and serum samples were collected at gestational weeks 30-31+6 to measure the levels of serum PLGF and sFlt-1 and calculate the sFlt-1/PLGF ratio. Results 1. Uterine artery blood flow parameters at gestational weeks 30-31+6 were significantly greater in the non-drug group than in the aspirin group, combined drug group, and control group (p

Introduction: The objective of the study was to compare the effects of orthodontic microimplant anchorage (MIA) and conventional extraoral arch anchorage (EAA) on tooth structure and oral inflammatory response in patients with Class II Division I malocclusion. Methods: A total of 104 patients with Class II malocclusion were enrolled and were randomly assigned to receive MIA or EAA treatments. Clinical efficacy was assessed at 6 months after treatment by measuring molar shift, convex distance, and hinge angle difference between maxillary and mandibular incisors. X-ray was performed for tissue evaluations. The levels of cell adhesion molecule-1 (CAM-1), matrix metalloproteinase-2 (MMP-2), and proinflammatory cytokines in gingival sulcus fluid were measured using enzyme-linked immunosorbent assay to assess inflammatory responses to the implants. Results: Our study demonstrated superior efficacy of MIA compared to EAA in terms of overall efficacy, molar shift, convex distance between upper and middle incisors, as well as hinge angle difference between upper and middle incisors. MIA also showed greater efficacy in reducing tissue fix-point measurements, including saddle point–nasal root point–superior alveolar seat point (SNA), alveolar seat point–nasal root point–inferior alveolar seat point (ANB), overlying (OJ), and overbite (OB). Conclusions: MIA is a novel orthodontic treatment that showed stronger efficacy in inducing molar shift and correcting soft/hard tissue positions, whilst generating suppressed inflammatory responses. Our study could have significant implications for practice in the orthodontic treatment of Class II malocclusion.

The carbon catabolite repression 4-negative on TATA-less transcription complex subunit 3 gene ( CONT3 ) plays a key role in regulating the mRNA transcription and protein translation of other genes. Mutations in CONT3 have also recently been implicated as a causative factor of intellectual developmental disorder with speech delay, autism, and dysmorphic facies (IDDSADF). However, to date, only a few CONT3 mutations have been reported to be associated with IDDSADF-related diseases. In the present case, we report a Chinese patient with developmental delay, verbal regression, and facial dysmorphism, in whom cerebral magnetic resonance imaging showed an expansion of the lateral ventricle. The patient was diagnosed with an IDDSADF-related disease caused by a de novo c.1616_1623del mutation in exon 14 of CONT3 , which was confirmed by whole-exome sequencing and direct Sanger sequencing. This case report is the first known documentation of a pathogenic mutation at the c.1616_1623del locus of CONT3 in the worldwide population. It provides a critical theoretical basis for the specific gene-based diagnosis of IDDSADF-related diseases and expands the mutation profile of CONT3 .

Renal ischemia-reperfusion (I/R) injury leads to irreversible brain damage with serious consequences. Activation of oxidative stress and release of inflammatory mediators are considered potential pathological mechanisms. Butylphthalide (NBP) has anti-inflammatory and antioxidant effects on I/R injuries. However, it is unclear whether NBP can effectively mitigate renal I/R secondary to brain injury as well as its mechanism, which are the aims of this study. Both renal I/R injury rats and oxygen and glucose deprivation cell models were established and pre-intervened NBP. The Morris water maze assay was used to detect behavior. Hippocampal histopathology and function were examined after renal I/R. Apoptosis and tube-forming capacity of brain microvascular endothelial cells (BMVECs) were tested. Immunohistochemistry and Western blot were used to measure protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) pathway and NOD-like receptor C2 (NOD2)/Mitogen-activated protein kinases (MAPK)/Nuclear factor kappa-B (NF-κB) pathway. NBP treatment attenuated renal I/R-induced brain tissue damage and learning and memory dysfunction. NBP treatment inhibited apoptosis and promoted blood-brain barrier restoration and microangiogenesis. Also, it decreased oxidative stress levels and pro-inflammatory factor expression in renal I/R rats. Furthermore, NBP enhanced BMVECs’ viability and tube-forming capacity while inhibiting apoptosis and oxidative stress. Notably, the alleviating effects of NBP were attributed to Nrf2/HO-1 pathway activation and NOD2/MAPK/NF-κB inhibition. This study demonstrates that NBP maintains BBB function by activating the Nrf2/HO-1 pathway and inhibiting the NOD2/MAPK/NF-κB pathway to suppress inflammation and oxidative stress, thereby alleviating renal I/R-induced brain injury.

In recent years, with the large-scale and high-intensity mining of coal resources, the problem of water accumulation in mining areas with high groundwater levels has become particularly prominent, which has had a serious impact on the surrounding ecological environment. In order to provide scientific basis for the restoration of the ecological environment, the study on the temporal and spatial evolution characteristics and influencing factors of the coal mining subsidence area with high groundwater level were carried out. Taking the whole mining area of Anhui Province as the research subject, based on Landsat TM/OLI remote sensing data, the NDWI and visual interpretation method were used to conduct surveys on the water accumulation area in the subsidence area from 1995 to 2020 (22 periods ) and 12 months in 2020 (12 periods) and the spatial information of waterlogging in the coal mining subsidence area in Anhui Province in recent 25 years was obtained. Combined with hydrological and rainfall data, the factors affecting the spatio-temporal evolution of waterlogging in the subsidence area were analyzed and discussed. The results show that: ① In the past 25 years, the area of accumulated water in the coal mining subsidence area in Anhui Province has been growing in three stages: slow, fast and stable. During the study period, the average stagnant area increased by about 6 times, from 18.95 km2 to 118.09 km2, with an average annual increase of 3.97 km2. ② From the time scale, the evolution of accumulation area in the subsidence area can be divided into three stages: the first stage (1995—2005), due to the fact that most of the accumulation water has not yet stabilized initially, the growth rate is relatively slow, with an average annual growth rate of 4.65%; In the second stage (2005—2013), based on the rapid growth of coal mining, the area of accumulation water has also entered a period of rapid growth, with an average annual growth rate of 6.64%; In the third stage (2013—2020), the growth rate has begun to decrease, and the accumulation water has gradually stabilized, with an average annual growth rate of 3.42%. From the spatial scale, the accumulation water is mainly concentrated in Huainan and Huaibei cities, accounting for about 70% of the total accumulated water area. ③The long-term factor for the change of the water accumulation is coal mining volume, while the main influencing factor in short time scale is atmospheric rainfall. ④The logistic regression curve was used to establish a prediction model for the water accumulation area of coal mining subsidence in Anhui Province. It is predicted that the coal mining subsidence water area in Anhui Province will still be in a low-speed growth stage in the future. By 2030, the accumulation area in the dry season will reach about 130 km2. The high-precision water accumulation information in the subsidence area was obtained, and its temporal and spatial evolution laws and influencing factors were analyzed, which can provide a scientific basis for the treatment of water accumulation in the coal mining subsidence area with high groundwater level and the ecological restoration of the subsidence area.

Nearly half of human cancers harbor p53 mutations, and mutant p53 (mutp53) promotes carcinogenesis, metastasis, tumor recurrence and chemoresistance. mutp53 is observed in 30% of breast carcinomas, including triple‐negative breast cancer (TNBC), and thus mutp53 is a promising target for treatment of TNBC. In this study, we investigated the effect of a phosphatidylinositide 3 kinase/mammalian target of rapamycin dual inhibitor, NVP‐BEZ235 (BEZ235), on two TNBC cell lines with mutp53: MDA‐MB‐231 and MDA‐MB‐468. Cell growth, migration and colony‐formation abilities were detected by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium bromide, scratch assay, transwell and soft agar assay, revealing that BEZ235 can inhibit the growth, migration and colony‐formation abilities of TNBC cells. In addition, BEZ235 caused degradation of mutp53 in these cells. We investigated the underlying mechanism by inhibiting proteasome function using MG132 and inhibiting autophagy using 3‐methyladenine and shRNAs. We observed that BEZ235 may induce autophagy through repression of the Akt/mammalian target of rapamycin signaling pathway. The observed interplay between mutp53 and autophagy in TNBC cells was examined further by knockdown of ATG5 and ATG7, revealing that degradation of mutp53 induced by BEZ235 may be independent of the ubiquitin–proteasome pathway and autophagy mediated by ATG5 and ATG7. Moreover, we found evidence of positive feedback between mutp53 and autophagy in TNBC cells. In conclusion, BEZ235 may exert antitumor effects against TNBC cells by targeting mutp53, and this may have implications for the development of future therapies.

Abstract Background Dihydroartemisinin (DHA), a derivate of artemisinin, is an effective antimalarial agent. DHA has been shown to exert anticancer activities to numerous cancer cells in the past few years, while the exact molecular mechanisms remain to be elucidated, especially in esophageal cancer. Methods Crystal violet assay was conducted to determine the cell viability of human esophageal cancer cell line Eca109 treated with DHA. Tumor-bearing nude mice were employed to evaluate the anticancer effect of DHA in vivo. Soft agar and crystal violet assays were used to measure the tumorigenicity of Eca109 cells. Flow cytometry was performed to evaluate ROS or cell cycle distribution. GFP-LC3 plasmids were delivered into Eca109 cells to visualize autophagy induced by DHA under a fluorescence microscope. The mRNA and protein levels of each gene were tested by qRT-PCR and western blot, respectively. Results Our results proved that DHA significantly reduced the viability of Eca109 cells in a dose- and time-dependent manner. Further investigation showed that DHA evidently induced cell cycle arrest at the G2/M phase in Eca109 cells. Mechanistically, DHA induced intracellular ROS generation and autophagy in Eca109 cells, while blocking ROS by an antioxidant NAC obviously inhibited autophagy. Furthermore, we found that telomere shelterin component TRF2 was down-regulated in Eca109 cells exposed to DHA through autophagy-dependent degradation, which could be rescued after autophagy was blocked by ROS inhibition. Moreover, the DNA damage response (DDR) was induced obviously in DHA treated cells. To further explore whether ROS or autophagy played a vital role in DHA induced cell cycle arrest, the cell cycle distribution of Eca109 cells was evaluated after ROS or autophagy blocking, and the results showed that autophagy, but not ROS, was essential for cell cycle arrest in DHA treated cells. Conclusion Taken together, DHA showed anticancer effect on esophageal cancer cells through autophagy-dependent cell cycle arrest at the G2/M phase, which unveiled a novel mechanism of DHA as a chemotherapeutic agent, and the degradation of TRF2 followed by DDR might be responsible for this cell phenotype.

Chronic arsenic exposure is associated with the increased risk of several types of cancer, among which, lung cancer is the most deadly one. Nuclear factor erythroid 2 like 1 (NFE2L1), a transcription factor belonging to CNC-bZIP family, regulates multiple important cellular functions in response to acute arsenite exposure. However, the role of NFE2L1 in lung cancer induced by chronic arsenite exposure is unknown. In this study, we firstly showed that chronic arsenite exposure (36 weeks) led to epithelial-mesenchymal transition (EMT) and malignant transformation in human bronchial epithelial cells (BEAS-2B). During the process of malignant transformation, the expression of long isoforms of NFE2L1 (NFE2L1-L) was elevated. Thereafter, BEAS-2B cells with NFE2L1-L stable knockdown (NFE2L1-L-KD) was chronically exposed to arsenite. As expected, silencing of NFE2L1-L gene strikingly inhibited the arsenite-induced EMT and the subsequent malignant transformation. Additionally, NFE2L1-L silencing suppressed the transcription of EMT-inducer SNAIL1 and increased the expression of E-cadherin. Conversely, NFE2L1-L overexpression increased SNAIL1 transcription but decreased E-cadherin expression. Collectively, our data suggest that NFE2L1-L promotes EMT by positively regulating SNAIL1 transcription, and is involved in malignant transformation induced by arsenite.

Sesquiterpenes constitute the principal components of the genus Ainsliaea, encompassing guaiane, germacrane, eudesmane, and polymer sesquiterpene lactones types. These secondary metabolites exhibit diverse pharmacological activities, including antitumor, antibacterial, anti-inflammatory, antiviral, antioxidant, hepatoprotective, and neuroprotective effects. Through a comprehensive literature search of the Web of Science, PubMed, SciFinder, and CNKI databases, it was discovered that there are as many as 145 main sesquiterpenoids in the genus Ainsliaea. However, the nuclear magnetic resonance (NMR) data for the sesquiterpenes in this genus have not been systematically compiled and summarized. Therefore, this review aims to highlight the chemical structures, NMR data, and pharmacological activities of sesquiterpenes in Ainsliaea. By meticulously analyzing published scholarly literature, our goal is to provide a solid foundation for further exploration of new sesquiterpenes and extensive utilization of this genus.

Pleocatenata, a new genus, is introduced with its type species, Pleocatenata chiangraiensis, which was isolated from withered twigs of two medicinal plants, Clerodendrum quadriloculare (Blanco) Merr (Verbenaceae) and Tarenna stellulata (Hook.f.) Ridl (Rubiaceae) in northern Thailand. The genus is characterized by mononematous, septate, brown or dark brown conidiophores, monotretic conidiogenous cells and catenate, obclavate, olivaceous to blackish brown conidia. Phylogenetic analysis of combined LSU, SSU, tef1-α, rpb2 and ITS sequence data showed Pleocatenata forms a distinct phylogenetic lineage in Pleosporales, Dothideomycetes. Therefore, we treat Pleocatenata as Pleosporales genera incertae sedis based on morphology and phylogenetic analyses. Descriptions and illustrations of the new taxa are provided, and it is compared with morphologically similar genera.

In this study, we investigated the serum vitamin D level in overweight individuals and its correlation with the incidence of nonalcoholic fatty liver disease (NAFLD). Between May 2020 and May 2021, the Department of Gastroenterology at the People's Hospital of Henan University of Traditional Chinese Medicine treated a total of 321 outpatients and inpatients with NAFLD, who were included in the NAFLD group, while 245 healthy ageand gender-matched individuals were included in the control group. All the data were collected for the relevant indices, including fasting plasma glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, alanine transaminase, and 25-hydroxy vitamin D (25[OH]D. The patients with NAFLD were divided into the normal BMI group, the overweight group, and the obese group, according to the body mass index, and the 25(OH)D levels were compared between the different groups. Spearman's correlation analysis was performed to analyze the correlation between the serum 25(OH)D level and NAFLD. Regarding the serum 25 (OH)D level, it was lower in the NAFLD group than in the control group ([18.36 + 1.41] µg/L vs [22.33 + 2.59] µg/L, t = -5.15, P<0.001), and was lower in the overweight group than in the normal group ([18.09 ± 5.81] µg/L vs [20.60 ± 4.16] µg/L, t = 0.26, P = 0.041). The serum 25(OH)D level was thus negatively correlated with the incidence of NAFLD in overweight individuals (r = 0.625, P<0.05). In conclusion, the level of 25(OH)D decreased in patients with NAFLD with increasing BMI (normal, overweight, obese). [ABSTRACT FROM AUTHOR]

Abstract In this paper, identifying the initial value for high dimension heat equation with inhomogeneous source on a spherical symmetric domain is investigated. The truncation regularization method is a powerful technique for solving this inverse problem. We prove the convergence estimates between the regularization solution and the exact solution under the prior and the posterior regularization parameter choice rulers. A numerical example is presented to validate the effectiveness of this method.

Renal ischemia-reperfusion (I/R) injury leads to irreversible brain damage with serious consequences. Activation of oxidative stress and release of inflammatory mediators are considered potential pathological mechanisms. Butylphthalide (NBP) has anti-inflammatory and antioxidant effects on I/R injuries. However, it is unclear whether NBP can effectively mitigate renal I/R secondary to brain injury as well as its mechanism, which are the aims of this study. Both renal I/R injury rats and oxygen and glucose deprivation cell models were established and pre-intervened NBP. The Morris water maze assay was used to detect behavior. Hippocampal histopathology and function were examined after renal I/R. Apoptosis and tube-forming capacity of brain microvascular endothelial cells (BMVECs) were tested. Immunohistochemistry and Western blot were used to measure protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) pathway and NOD-like receptor C2 (NOD2)/Mitogen-activated protein kinases (MAPK)/Nuclear factor kappa-B (NF-κB) pathway. NBP treatment attenuated renal I/R-induced brain tissue damage and learning and memory dysfunction. NBP treatment inhibited apoptosis and promoted blood-brain barrier restoration and microangiogenesis. Also, it decreased oxidative stress levels and pro-inflammatory factor expression in renal I/R rats. Furthermore, NBP enhanced BMVECs' viability and tube-forming capacity while inhibiting apoptosis and oxidative stress. Notably, the alleviating effects of NBP were attributed to Nrf2/HO-1 pathway activation and NOD2/MAPK/NF-κB inhibition. This study demonstrates that NBP maintains BBB function by activating the Nrf2/HO-1 pathway and inhibiting the NOD2/MAPK/NF-κB pathway to suppress inflammation and oxidative stress, thereby alleviating renal I/R-induced brain injury. [ABSTRACT FROM AUTHOR]