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Abstract The diagnosis of Autism Spectrum Disorder (ASD) is mainly based on some diagnostic scales and evaluations by professional doctors, which may have limitations such as subjectivity, time, and cost. This research introduces a novel assessment and auto-identification approach for autistic children based on the appearance of children, which is a relatively objective, fast, and cost-effective approach. Initially, a custom social interaction scenario was developed, followed by a facial data set (ACFD) that contained 187 children, including 92 ASD and 95 children typically developing (TD). Using computer vision techniques, some appearance features of children including facial appearing time, eye concentration analysis, response time to name calls, and emotional expression ability were extracted. Subsequently, these features were combined and machine learning methods were used for the classification of children. Notably, the Bayes classifier achieved a remarkable accuracy of 94.1%. The experimental results show that the extracted visual appearance features can reflect the typical symptoms of children, and the automatic recognition method can provide an auxiliary diagnosis or data support for doctors.

Abstract Background 46,XX complete gonadal dysgenesis (46,XX-CGD) is a rare disorder of sexual development (DSD) characterized by primary amenorrhea and a lack of spontaneous pubertal development in individuals with a 46,XX karyotype despite the presence of female internal and external genitalia due to failure of bilateral ovarian development. The condition is genetically heterogeneous, and in most cases, its etiology is unknown. Determining the genetic cause would provide insights into potential targets for genetic diagnosis and counseling. Methods To clarify the molecular mechanisms of 46,XX complete gonadal dysgenesis in the population of China, whole-exome sequencing (WES) was performed on DNA samples from patients with 46,XX-CGD. In silico analysis was conducted to predict the pathogenicity of the variants. Results We recruited 20 patients with 46,XX-CGD and identified 8 variants in 6 genes, including three homozygous variants in MCM9, POF1B, and PSMC3IP; compound heterozygous variants in TWNK; and three heterozygous variants in TP63 and INSRR, from 7 patients. These variants included 3 recurrent variants and 5 novel variants. Conclusions This study identified several novel variants, broadening the variant spectrum of 46,XX-CGD. 46,XX-CGD is a genetically heterogeneous condition, and WES is a powerful tool for determining its genetic etiology. The results of this study will aid researchers and clinicians in genetic counseling and suggest that WES is valuable for detecting 46,XX-CGD, which may lead to early interventions for patients.

Background and aims: Patients with peripheral artery disease (PAD) presented overall muscle weakness and reduced physical performance. Previous study focused on the impact of muscle weakness on outcomes of established PAD, however the relationship between compromised muscle function and incident PAD remained unclear. Methods: A prospective study involving 430,886 participants aged 40–69 y from UK biobank was conducted. The main outcome was incident PAD. Grip strength and walking pace were used as indicators for muscle function. Grip strength was measured using a Jamar J00105 hydraulic hand dynamometer, while walking pace was self-reported by the participants. Cox proportional hazard models were employed to investigate the relationship between grip strength, walking pace, and incident PAD. Results: A total of 430,886 individuals were included in the final analysis. The mean age of the participants were 56.44 years, and 55.3 % were female. Over a median follow-up period of 13.81 years, 5,661 participants developed PAD. Higher grip strength, whether absolute or relative, exhibited a dose-dependent inverse association with incident PAD. Each 1 kg increment in absolute grip strength and each 0.01 kg/kg increase in relative grip strength were associated with reduced PAD risk by 2 % (HR: 0.98; 95 % CI [0.97–0.98]) and 83 % (HR: 0.17; 95 % CI [0.13–0.23]), respectively. Slow walking pace significantly correlated with increased PAD risk, while brisk walking pace was associated with decreased PAD risk. Conclusion: Absolute grip strength, relative grip strength and walking pace were inversely associated with the risk of incident PAD.

The traditional Chinese medicine (TCM) formulation Shengqiyichang Decoction (SQYCD) has been reported to stimulate host immunity, and it has been administered for the treatment of colorectal cancer (CRC). Here, we applied network and bioinformatics analyses to elucidate the mechanisms by which SQYCD ameliorates CRC and validated its modes of action via in vivo and in vitro experiments. We identified 46 active compounds in SQYCD and selected 237 proteins as potential therapeutic targets in CRC, most notably p38 mitogen-activated protein kinase (p38⍺). Bioinformatics analyses demonstrated differential expression in CRC tissues and prognostic value of the genes encoding TNFα, MAPK14, CASP-3, MAPK1, AKT1, PRKACA, VEGF, IL-6, EGFR and ESR1. We then plotted receiver operating curves (ROC) and time-ROC for the differentially expressed genes (DEGs) ESR1 and AKT1 to predict the progress of CRC. We speculated that the AKT/p38α-MAPK signaling pathway is associated with the clinical prognosis of CRC. In a mouse model, we found that SQYCD inhibits CRC tumor growth by increasing CD4+ and CD8+ T cell abundance and decreasing the ratio of T-regulatory cells (Tregs) in the tumor microenvironment. In cultured mouse CRC cells, SQYCD selectively upregulated levels of the CRC-associated protein lymphocyte antigen 6 family member G6D, while the AKT activator SC-79 reversed this effect. The discoveries made herein suggest that SQYCD exerts a therapeutic effect in CRC by inhibiting Treg recruitment via inhibition of the AKT/p38α/LY6G6D signaling axis.

Abstract BackgroundAllergic diseases are associated with an increased susceptibility to respiratory tract infections. Although allergen immunotherapy (AIT) alters the course of allergies, there is limited evidence from clinical practice demonstrating its ability to enhance the host defense against pathogens. ObjectiveThe aim of this study was to investigate the protective effect of AIT against viral infection in patients with allergic rhinitis (AR) and allergic asthma (AS) based on clinical evidence. MethodsA multicenter, questionnaire-based survey was conducted during a tremendous surge in COVID-19 cases between February 10, 2023, and March 15, 2023, in 81 centers across China recruiting healthy volunteers and patients with AR and AS to investigate the clinical outcomes of COVID-19 infection. ResultsOf 10,151 participants recruited in the survey, 3654 patients and 2192 healthy volunteers who tested positive for COVID-19 were included in this analysis after screening. Overall, no significant differences in COVID-19 outcomes were observed between patients and healthy volunteers. An additional 451 patients were excluded due to their use of biologics as the sole add-on treatment, leaving 3203 patients in the further analysis. Of them, 1752 were undergoing routine medication treatment (RMT; the RMT group), whereas 1057 and 394 were receiving AIT and a combination of AIT and omalizumab (OMA) as adjunct therapies to RMT, respectively (AIT+RMT and AIT+OMA+RMT groups). The AIT group showed milder COVID-19 symptoms, shorter recovery periods, and a lower likelihood of hospitalization or emergency department visits than the RMT group (all PPPP ConclusionsOur multicenter observational study provides valuable clinical evidence supporting the protective effect of AIT against COVID-19 infection in patients with AR and AS.

Abstract Background Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated. Methods The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation. Results DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, l-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota. Conclusion DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

As the reform of electricity marketization advances, the virtual power plant (VPP), as an emerging market participant, is being progressively incorporated into the trading scope of both the electricity spot market (ESM) and the reserve market (RM). Due to its flexible regulation capabilities, the bidding strategies of VPPs in the electricity market are complex and variable, presenting new challenges to the joint operation of power markets. In this context, first, based on the interactive game relationships among multiple market entities under the operating mechanisms of the spot and reserve markets, this paper designs a principal-follower game framework for transactions in these markets with the VPP as the main entity. Second, it constructs a two-level joint optimized bidding strategy model for VPP participation in the spot and reserve markets, where the inner layer is the VPP’s optimized bidding strategy model aiming to maximize the total revenue from the spot and reserve markets; the outer layer is the spot and reserve market clearing model targeting the minimization of the total electricity purchasing cost for society. Finally, the simulation case analysis shows that the proposed method can achieve joint optimal operation of the electricity spot and reserve markets by considering the VPP bidding strategy, resulting in a 1.42% reduction in the total electricity purchase cost of the power market.

Pollinosis is one of the common allergic diseases, and its morbidity continues to increase. Studies have demonstrated that air pollution is a key environmental factor that leads to the increased prevalence of pollinosis. Air pollutants and pollen allergens exert synergistic effects in stimulating allergic responses in susceptible individuals. In this article, we analyzed the relationship between air pollution and pollinosis based on the latest studies, and elaborated potential mechanisms on how air pollution increases the incidence of pollinosis and aggravates allergic reactions. Air pollutants can increase both pollen production and the levels of allergenic proteins, and enhance allergenicity of pollen allergens through structural alterations or chemical modifications. The potential mechanisms of air pollutants exacerbating pollen allergies are as follows: Air pollutants may disrupt the barrier function of the respiratory epithelium and facilitate the penetration of pollen allergens into deeper tissues. Additionally, they may accelerate the process of the release of pollen allergy-related cytokines, promoting T helper 2 (Th2) cell differentiation and exacerbating inflammatory responses in the airways. Given the limitations of existing research, future prospective studies are needed to explore the effects of mixed pollutants and different types of pollutants on pollen, and the response mechanisms of allergy-related cells and cytokines to different pollutant categories. The findings would provide a comprehensive understanding of the impacts of air pollution on pollen allergies and scientific evidence for effective protection of the heath of pollinosis patients.

The cryopreservation of Anthurium andraeanum germplasm resources is extremely important for the production and selection of new varieties. At present, the cryopreservation procedure for the callus of A. andraeanum has not been established. In this study, the leaves of A. andraeanum were used as explants to culture the callus. The cryopreservation procedure of the callus by vitrification was initially established by using the orthogonal experimental method of four factors and three levels in the preculture, loading, and dehydration steps. Furthermore, the vitrification-based cryopreservation was optimized by changing the preculture temperature and loading solution and adding exogenous substances to the plant vitrification solution (PVS2). In this procedure, the callus was precultured at 25 °C for 2 d, and loaded in 50% PVS2 at 25 °C for 60 min. The callus was dehydrated with PVS2 containing 0.08 mM reduced glutathione (GSH) at 0 °C for 60 min. After rapid-cooling in liquid nitrogen for 1 h, it was rapid-warming in a water bath at 40 °C for 90 s and unloaded for 30 min. After 1 d of recovery, the cell relative survival rate of the cryopreserved callus was 64.60%. The results provide a valuable basic and effective method for the long-term conservation of A. andraeanum germplasm resources.

This study investigates the electrical characteristics observed in n-channel and p-channel ferroelectric field effect transistor (FeFET) devices fabricated through a similar process flow with 10 nm of ferroelectric hafnium zirconium oxide (HZO) as the gate dielectric. The n-FeFETs demonstrate a faster complete polarization switching compared to the p-channel counterparts. Detailed and systematic investigations using TCAD simulations reveal the role of fixed charges and interface traps at the HZO-interfacial layer (HZO/IL) interface in modulating the subthreshold characteristics of the devices. A characteristic crossover point observed in the transfer characteristics of n-channel devices is attributed with the temporary switching between ferroelectric-based operation to charge-based operation, caused by the pinning effect due to the presence of different traps. This experimental study helps understand the role of charge trapping effects in switching characteristics of n- and p-channel ferroelectric FETs.

Background: Diallyl trisulfide (DATS), a compound derived from garlic, has been demonstrated its anti-cancer properties. While it has been shown to inhibit the expression of epidermal growth factor receptor (EGFR) in various cancers, its effects on osteosarcoma (OS) cells remain unclear. This study aimed to investigate the impacts of DATS on OS cells growth, migration, invasion, epithelial-mesenchymal transition (EMT) and autophagy, as well as its underlying mechanisms which was involving in the EGFR/PI3K/AKT/mTOR pathway. Methods: In this study, human osteosarcoma cells (143B) were treated with different concentrations of DATS (10, 50, 100 and 200 μM) for 24 and 48 h, respectively. Cell viability was measured using CCK8, the half lethal concentration was selected for the following experiments. Wound healing and transwell assays were performed to evaluate migration and invasion abilities, while flow cytometry was used to measure apoptosis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting, and confocal imaging were employed to analyze the related mRNA and protein expression levels of epithelial-mesenchymal transition (EMT), EGFR/Phosphoinositide 3 kinase (PI3K)/AKT/Mammalian target of rapamycin (mTOR) signaling pathway and autophagy-related markers. Results: DATS significantly inhibited proliferation, migration and EMT in osteosarcoma cells. Additionally, DATS promoted cell apoptosis and induced autophagy, which could be rescued by the autophagy inhibitor 3-methyladenine (3-MA). Moreover, DATS treatment led to the inactivation of the EGFR/PI3K/AKT/mTOR pathway in osteosarcoma cells. Conclusions: This study demonstrated that DATS inhibited osteosarcoma cell growth, migration and EMT, but inducing apoptosis and autophagy. These effects were mediated by the inactivation of the EGFR/PI3K/AKT/mTOR signaling pathway. These findings suggested that DATS could serve as a potential therapeutic agent for osteosarcoma treatment.

BackgroundAging is an important factor in the development of Alzheimer’s disease (AD). The senescent cells can be recognized and removed by NK cells. However, NK cell function is gradually inactivated with age. Therefore, this study used senescence as an entry point to investigate how NK cells affect AD.MethodsThe study validated the correlation between cognition and aging through a prospective cohort of the National Health and Nutrition Examination Survey database. A cellular trajectory analysis of the aging population was performed using single-cell nuclear transcriptome sequencing data from patients with AD and different ages. The genome-wide association study (GWAS) cohort of AD patients was used as the outcome event, and the expression quantitative trait locus was used as an instrumental variable. Causal associations between genes and AD were analyzed by bidirectional Mendelian randomization (MR) and co-localization. Finally, clinical cohorts were constructed to validate the expression of key genes.ResultsA correlation between cognition and aging was demonstrated using 2,171 older adults over 60 years of age. Gene regulation analysis revealed that most of the highly active transcription factors were concentrated in the NK cell subpopulation of AD. NK cell trajectories were constructed for different age populations. MR and co-localization analyses revealed that CHD6 may be one of the factors influencing AD.ConclusionWe explored different levels of AD and aging from population cohorts, single-cell data, and GWAS cohorts and found that there may be some correlations of NK cells between aging and AD. It also provides some basis for potential causation.

Early life nutritional supplementation can significantly improve pigeon health. Both the nutritional crops of parental pigeons and the intestinal development of squabs play key roles in the growth rate of squabs. Tea polyphenols (TPs), as natural plant extracts, exhibit potential biological activities. However, the impact of TPs on the intestinal function of squabs is not known. This study evaluated the effects of TPs on growth performance, immunity, antioxidation, and intestinal function in squabs. A total of 432 young pigeons (1 day old) were divided into four groups: a control group (fed a basic diet) and three treatment groups (low, medium, and high dose groups; 100, 200, and 400 mg/kg TPs, respectively). On the 28th day, samples of serum, mucosal tissue, and digests from the ileum of squabs were collected for analysis. The results revealed that TP supplementation significantly reduced the feed-to-meat ratio and improved the feed utilization rate and serum biochemical indices in squabs. Additionally, it enhanced the intestinal barrier function of birds by promoting intestinal development and integrity of tight junctions and regulating digestive enzyme activities and intestinal flora. Mechanistically, TPs activated the Nrf2-ARE signaling pathway, which may be associated with improved antioxidant and immune responses, correlating with an increased abundance of Candida arthritis and Corynebacterium in the ileum.

The sampling technique is commonly used in research investigations to more accurately estimate data with greater precision, at a lower cost and in less time. In plant DUS (distinctness, uniformity, and stability) testing, many quantitative characteristic data usually need to be obtained through individual measurements. However, there is currently no scientific method for determining the appropriate sampling size. The minimum number of testing samples for DUS testing was calculated based on the theory of sample size in descriptive studies and was validated through simple random sampling. The results show that the quantitative characteristics for the edible mushroom Shiitake (Lentinula edodes) in DUS testing were uniform. The calculated results show that 10 fruiting bodies for a single measurement were sufficient. Furthermore, the outcomes of the random sampling revealed that the mean of 10 samples did not significantly differ from the mean of all data. When the sample size exceeded 10, Cohen’s kappa statistic suggested that the conclusion of distinctness was very close to the near-perfect agreement. Reducing the number of samples did not affect the uniform assessment. This study suggests that the theory of sample size in descriptive studies could be applied to calculate the minimum sample size in DUS testing, and for Shiitake DUS testing, measuring 10 fruiting bodies was sufficient.

Content addressable memory (CAM) is widely used in associative search tasks due to its parallel pattern matching capability. As more complex and data‐intensive tasks emerge, it is becoming increasingly important to enhance CAM density for improved performance and better area efficiency. To reduce the area overheads, various nonvolatile memory (NVM) devices, such as ferroelectric field‐effect transistors (FeFETs), are used in CAM design. Herein, a novel ultracompact 1FeFET CAM design that enables parallel associative search and in‐memory hamming distance calculation is used, as well as a multibit CAM for exact search using the same CAM cell. The proposed CAM design leverages the 1FeFET1R structure, and compact device designs that integrate the series resistor current limiter into the intrinsic FeFET structure are demonstrated to turn the 1FeFET1R structure into an effective 1FeFET cell. A two‐step search operation of the proposed binary and multibit 1FeFET CAM array through both experiments and simulations is proposed, showing a sufficient sensing margin despite unoptimized FeFET device variation. In genome pattern matching applications, using the hyperdimensional computing paradigm, the design results in a 89.9× speedup and 66.5× improvement in energy efficiency over the state‐of‐the‐art alignment tools on GPU.

Maximizing rice yield potential has always been the focus of high-yield rice cultivation research. For high-yield rice cultivation and breeding, more research into the link between yield and yield components is essential. In this experiment, 38 rice varieties with different yield types and 185 rice varieties as materials were chosen. The relationships between yield and yield components were studied. The regulation effects of total nitrogen application rate (TNAR) on yield and yield components were observed. The results showed that (1) the grain yield of high-yield varieties was 189.3−195.6%, 76.1−77.7%, and 27.0−28.7% higher than that of super-low-yield, low-yield, and medium-yield varieties, respectively. Compared with rice varieties with other yield types, rice varieties with high-yield type have a higher total number of spikelets. (2) The spikelet number per panicle and total number of spikelets were significantly positively linked with grain yield, but significantly negatively correlated with filled grains and grain weight. (3) With an increase in TNAR (0−340 kg ha−1), the panicles, spikelet number per panicle, and total spikelets of rice varieties with different yield types increased gradually, and the filled grains and grain weight decreased gradually. The higher the TNAR, the more obvious the decrease in filled grains and grain weight. The grain yield of rice varieties with different yield types was the highest under the TNAR at 250 kg ha−1. The main factor contributing to its high yield was the substantial increase in total spikelets. The above results showed that increasing the spikelet number per panicle and total spikelets played a material role in improving rice yield.

Objectives: The aim of this study was to investigate the dose-response relationship of admission fasting glucose (FBG) with corona virus disease 2019 (COVID-19) mortality and to further evaluate potential interactions of hyperglycemia with inflammation and hypercoagulation on COVID-19 outcomes. Methods: This retrospective study included 2555 consecutively hospitalized patients with COVID-19, until death or discharge, in Wuhan Union hospital between January 1 and April 9, 2020. The poor early outcomes included admission to intensive care unit, intubation, and deaths occurring within 28 days. We used splines nested in Cox regression to visualize dose-response associations and generalized additive models to fit three-dimensional (3D) trend plots for joint effects of FBG with markers of inflammation and coagulation. Results: J-shaped associations existed between hospitalized mortality or poor early outcomes and FBG with a nadir at 5 mmol/L, which were more evident in women. 3D plots demonstrated significant joint effect trends, and patients with hyperglycemia and high neutrophil-lymphocyte ratio, C-reactive protein, lactate dehydrogenase, procalcitonin, d-dimer, and interleukin-6 had 7.4-25.3-fold risks; the proportions of joint associations attributed to additive interactions reached 30% to 54%. Conclusions: FBG was associated with hospitalized mortality and poor early outcomes in a J-shaped manner, and a combination of hyperglycemia, inflammation, hypercoagulation, and cytokines conferred a dramatically higher risk.

Background: Complete androgen insensitivity syndrome (CAIS, OMIM; 300068) is a disorder of sex development with X-linked recessive inheritance. Cases of CAIS usually present as female phenotype, with primary amenorrhea and/or inguinal hernia. Family aggregation is a rare scenario.Methods: This study is a retrospective analysis of CAIS cases in a three-generation pedigree. The patients’ genomes were determined by sequencing the androgen receptor (AR) gene. The clinical data of the patients, including manifestations, hormone levels, and AR variants, were analyzed.Results: Sixteen people in this family were involved. A deletion variant (c.1847_1849del; p. Arg616del) was identified in exon 3 of AR, which encodes the DNA binding domain. Until now, four patients and four carriers have been identified in three generations of this family. All the patients live as female, and one has developed gonadal malignancy.Conclusion: The present study identified a deletion variant in three generations of a family with CAIS, including four carriers and four patients. This study verified the genetic pattern and the corresponding clinical characteristics of CAIS. Furthermore, a case with gonadal malignancy was discovered. The information on diagnosis and treatment in this pedigree is useful for prenatal diagnosis and genetic counseling of similar families.

Hardware security is importance with outsourcing of integrated circuit fabrication to various foundries. Here, the authors propose a compact encryption logic based on the active interconnects constructed with ferroelectric field-effect transistors.

Background: Uterine malformations can be divided into the dysmorphic uterus (U1); septate uterus (U2); bicorporeal uterus (U3); hemi-uterus (U4) and hypoplastic uterus (U5) with clinical significance ranging from mild to severe. This study aims to investigate whether different types of uterine malformations in infertile patients who have undergone hysteroscopic and laparoscopic surgery are associated with different pregnancy outcomes. Methods: This is a retrospective study of patients with uterine malformations and infertility admitted to the Department of Gynecology of Peking Union Medical College Hospital between January 2003 and December 2020. Patients were followed through 31 October 2021. Those lost to follow-up or who had not tried to become pregnant were excluded. Fertility outcomes included pregnancy rate, live birth rate and miscarriage rate. Fertility outcomes among patients experiencing different uterine anomalies were compared using one-way analysis of variance (ANOVA). Results: A total of 161 patients were included, of whom 62 (38.5%) had no other infertility-related factors except a uterine malformation. The rate of concomitant endometriosis (36.0%) was significantly higher than among the non-specific infertile population (p < 0.05). One hundred seventeen patients achieved a total of 151 pregnancies postoperatively. The total pregnancy rate was 77.5%, and the live birth rate was 73.4%. The pregnancy and miscarriage rates in patients with uterine septum with a single cervix were 76.0% and 15.5%, respectively; 75.0% and 37.5% among patients with unicornuate uterus with a single cervix; 88.9% and 9.5% among patients with uterine septum with a double cervix; 100% and 25% among patients with uterus duplex with double cervix; and 50% and 25% among patients with bicornuate uterus with a single cervix. Patients were grouped into either the septum group or the unicornuate uterus group dependent on the ability to enlarge the uterine cavity by surgery. The pregnancy rates for the two groups were 78.1% and 80.6%, respectively, with no significant difference noted (p = 0.599), although there was a significant difference in the miscarriage rate (14.4% vs. 33.3%) (p = 0.002). Conclusion: This retrospective analysis can help to illustrate differences in pregnancy outcomes of different types of uterine malformations although it lacked a proper control group. The non-obstructive uterine malformation may not be a dominant cause of infertility, and the volume of the uterine cavity may be a key factor leading to first-trimester miscarriage, rather than an important causative factor for infertility.

An accurate and reliable estimation of photovoltaic models holds immense significance within the realm of energy systems. In pursuit of this objective, a Boosting Flower Pollination Algorithm (BFPA) was introduced to facilitate the robust identification of photovoltaic model parameters and enhance the conversion efficiency of solar energy into electrical energy. The incorporation of a Gaussian distribution within the BFPA serves the dual purpose of conserving computational resources and ensuring solution stability. A population clustering strategy is implemented to steer individuals in the direction of favorable population evolution. Moreover, adaptive boundary handling strategies are deployed to mitigate the adverse effects of multiple individuals clustering near problem boundaries. To demonstrate the reliability and effectiveness of the BFPA, it is initially employed to extract unknown parameters from well-established single-diode, double-diode, and photovoltaic module models. In rigorous benchmarking against eight control methods, statistical tests affirm the substantial superiority of the BFPA over these controls. Furthermore, the BFPA successfully extracts model parameters from three distinct commercial photovoltaic cells operating under varying temperatures and light irradiances. A meticulous statistical analysis of the data underscores a high degree of consistency between simulated data generated by the BFPA and observed data. These successful outcomes underscore the potential of the BFPA as a promising approach in the field of photovoltaic modeling, offering substantial enhancements in both accuracy and reliability.

IntroductionComplete 17α-hydroxylase deficiency (17OHD) is relatively common, with typical juvenile female genitalia, severe hypertension, hypokalemia, and the absence of sexual development, but partial (or non-classical) 17OHD (p17OHD) is extremely rare. The p17OHD patients can present with a broad spectrum of symptoms in 46,XX karyotype including various degree of spontaneous breast development after puberty, recurrent ovarian cysts, oligomenorrhea and infertility depending on specific gene mutations and other influencing factors.MethodsThis paper is a retrospective analysis of p17OHD cases from 1997 to 2021 in a Chinese tertiary hospital. Eight patients were recruited from unrelated families according to clinical data. Genotypes of patients were determined by sequencing the CYP17A1 genes. Clinical characteristics were summarized based on manifestations, hormone profiles, and responses to treatments.ResultsAll seven post-pubertal patients had abnormal menses. All patients had enlarged multilocular ovaries, and six (6/8) had a history of ovarian cystectomy prior to a definite diagnosis of p17OHD. All eight patients’ sex hormone levels were in accord to hypogonadism with mildly elevated follicle-stimulating hormone levels, and oral contraceptives effectively suppressed the ovarian cysts. Of the four patients who underwent plasma renin activity tests, all showed results below the reference range. Fourteen alleles with a CYP17A1 mutation were found. Exon 6 was the most frequent mutation site (5/14), and four out of these five mutations were c.985_987delTACinsAA, being the most common one. In Case 2, c.1220dupA was a newly reported mutation of CYP17A1.Conclusions46,XX p17OHD patients were born with highly fragile ovarian reserve due to diverse mutations of CYP17A1. However, their multi-ovarian cysts can be managed conservatively for fertility preservation. This study focuses on p17OHD in 46,XX by locating the complex genetic causes in novel mutations, summarizing the puzzling spectrum of clinical manifestations, and illustrating the significance of fertility preservation in these scarce cases.

BackgroundAlzheimer’s disease is the most common neurodegenerative disease worldwide. Metabolic syndrome is the most common metabolic and endocrine disease in the elderly. Some studies have suggested a possible association between MetS and AD, but few studied genes that have a co-diagnostic role in both diseases.MethodsThe microarray data of AD (GSE63060 and GSE63061 were merged after the batch effect was removed) and MetS (GSE98895) in the GEO database were downloaded. The WGCNA was used to identify the co-expression modules related to AD and MetS. RF and LASSO were used to identify the candidate genes. Machine learning XGBoost improves the diagnostic effect of hub gene in AD and MetS. The CIBERSORT algorithm was performed to assess immune cell infiltration MetS and AD samples and to investigate the relationship between biomarkers and infiltrating immune cells. The peripheral blood mononuclear cells (PBMCs) single-cell RNA (scRNA) sequencing data from patients with AD and normal individuals were visualized with the Seurat standard flow dimension reduction clustering the metabolic pathway activity changes each cell with ssGSEA.ResultsThe brown module was identified as the significant module with AD and MetS. GO analysis of shared genes showed that intracellular transport and establishment of localization in cell and organelle organization were enriched in the pathophysiology of AD and MetS. By using RF and Lasso learning methods, we finally obtained eight diagnostic genes, namely ARHGAP4, SNRPG, UQCRB, PSMA3, DPM1, MED6, RPL36AL and RPS27A. Their AUC were all greater than 0.7. Higher immune cell infiltrations expressions were found in the two diseases and were positively linked to the characteristic genes. The scRNA-seq datasets finally obtained seven cell clusters. Seven major cell types including CD8 T cell, monocytes, T cells, NK cell, B cells, dendritic cells and macrophages were clustered according to immune cell markers. The ssGSEA revealed that immune-related gene (SNRPG) was significantly regulated in the glycolysis-metabolic pathway.ConclusionWe identified genes with common diagnostic effects on both MetS and AD, and found genes involved in multiple metabolic pathways associated with various immune cells.

JAK/STAT signaling pathways are closely associated with multiple biological processes involved in cell proliferation, apoptosis, inflammation, differentiation, immune response, and epigenetics. Abnormal activation of the STAT pathway can contribute to disease progressions under various conditions. Moreover, tofacitinib and baricitinib as the JAK/STAT inhibitors have been recently approved by the FDA for rheumatology disease treatment. Therefore, influences on the STAT signaling pathway have potential and perspective approaches for diverse diseases. Chinese herbs in traditional Chinese medicine (TCM), which are widespread throughout China, are the gold resources of China and have been extensively used for treating multiple diseases for thousands of years. However, Chinese herbs and herb formulas are characterized by complicated components, resulting in various targets and pathways in treating diseases, which limits their approval and applications. With the development of chemistry and pharmacology, active ingredients of TCM and herbs and underlying mechanisms have been further identified and confirmed by pharmacists and chemists, which improved, to some extent, awkward limitations, approval, and applications regarding TCM and herbs. In this review, we summarized various herbs, herb formulas, natural compounds, and phytochemicals isolated from herbs that have the potential for regulating multiple biological processes via modulation of the JAK/STAT signaling pathway based on the published work. Our study will provide support for revealing TCM, their active compounds that treat diseases, and the underlying mechanism, further improving the rapid spread of TCM to the world.

Abstract Background Repetitive transcranial magnetic stimulation (rTMS) is acknowledged to be crucial to manage freezing of gait (FOG) and cognitive impairment for patients with Parkinson's disease (PD), but its effectiveness is unclear. Objective To determine the effects of rTMS on FOG and cognitive function in people with PD and to investigate potential factors that modulate the rTMS effects. Methods Databases searched included PubMed, Web of Science, EMBASE, and the Cochrane Library from inception to December 31, 2021. Eligible studies include a controlled randomized clinical trial of rTMS intervention for FOG and cognitive dysfunction in PD patients. The weighted mean difference (WMD) with 95% confidence intervals (CI) were calculated with fixed‐effects models. The outcome of the study included gait and cognitive assessments. Results Sixteen studies with a total of 419 patients were included. Fixed‐effects analysis revealed that rTMS was effective in improving freezing of gait questionnaire scores (short‐term effect: WMD = −0.925, 95% CI: −1.642 to −0.209, p = .011; long‐term effect: WMD = −2.120, 95% CI: −2.751 to −1.489, p = .000), 10‐m walking time (short‐term effect: WMD = −0.456, 95% CI: −0.793 to −0.119, p = .008; long‐term effect: WMD = −0.526, 95% CI: −0.885 to −0.167, p = .004), Timed Up‐and‐Go scores (short‐term effect: WMD = −1.064, 95% CI: −1.555 to −0.572, p = .000; long‐term effect: WMD = −1.097, 95% CI: −1.422 to −0.772, p = .000), Montreal cognitive assessment (WMD = 3.714, 95% CI: 2.567 to 4.861, p = .000), and frontal assessment battery (WMD = −0.584, 95% CI: −0.934 to −0.234, p = .001). Conclusions RTMS showed a beneficial effect on FOG and cognitive dysfunction in parkinsonism. However, the optimal rTMS protocol has not been determined and further high‐quality studies are needed.

Metabolic reprogramming is a vital hallmark of cancer, and it provides the necessary energy and biological materials to support the continuous proliferation and survival of tumor cells. NR4A1 is belonging to nuclear subfamily 4 (NR4A) receptors. NR4A1 plays diverse roles in many tumors, including melanoma, colorectal cancer, breast cancer, and hepatocellular cancer, to regulate cell growth, apoptosis, metastasis. Recent reports shown that NR4A1 exhibits unique metabolic regulating effects in cancers. This receptor was first found to mediate glycolysis via key enzymes glucose transporters (GLUTs), hexokinase 2 (HK2), fructose phosphate kinase (PFK), and pyruvate kinase (PK). Then its functions extended to fatty acid synthesis by modulating CD36, fatty acid-binding proteins (FABPs), sterol regulatory element-binding protein 1 (SREBP1), glutamine by Myc, mammalian target of rapamycin (mTOR), and hypoxia-inducible factors alpha (HIF-1α), respectively. In addition, NR4A1 is involving in amino acid metabolism and tumor immunity by metabolic processes. More and more NR4A1 ligands are found to participate in tumor metabolic reprogramming, suggesting that regulating NR4A1 by novel ligands is a promising approach to alter metabolism signaling pathways in cancer therapy. Basic on this, this review highlighted the diverse metabolic roles of NR4A1 in cancers, which provides vital references for the clinical application.

Abstract Background Malignant struma ovarii (MSO) is a unique type of ovarian malignancy that data on the survival outcome is limited and management strategy remains controversial due to its extreme rarity. Methods To investigate the clinical characteristics and treatment options in patients with MSO confined to the ovary, while also evaluating the recurrent-free survival (RFS) and overall survival (OS) rate in this population, a retrospective study was conducted. One hundred twenty-five cases of MSO confined to the ovary were enrolled and their clinical characteristics, treatment strategies, and results of follow-up were analyzed. OS and RFS were assessed by Kaplan-Meier analyses and Cox regression models. Results The most common pathological subtype in this cohort was papillary carcinoma (44.8%). Other reported subtypes, in order of prevalence, were follicular variant of papillary carcinoma, follicular carcinoma, and mixed follicular-papillary carcinoma. Surgical treatment options varied in this cohort that 8.0% of the patients received ovarian cystectomy, 33.6% underwent unilateral salpingo-oophorectomy (USO), 5.6% received bilateral salpingo-oophorectomy (BSO), 21.6% received total abdominal hysterectomy with BSO (TAH/BSO), and 17.6% were treated with debulking surgery; 20.0% of them received radioiodine therapy (RAI). Twenty-seven patients experienced recurrence with a median RFS of 14.0 years (95% confidence interval [CI], 9.5–18.5). The 5-year and 10-year recurrent rate were 27.1, 35.2%, respectively. Eight patients died during follow-up, with five attributed to MSO; the 5-year, 10-year, and 20-year OS rate was 95.3, 88.7 and 88.7%, respectively. However, the univariate and multivariate Cox regression showed no potential risk factor for RFS and OS. Conclusion Patients with MSO confined to the ovary had an excellent survival outcome, despite varied treatment strategies, and the recurrent rate was relatively high. We recommend USO as the preferred surgical option in this population since more aggressive surgery does not improve outcomes and the benefits of RAI are uncertain.

The determination of the grades and interval of quantitative characteristics is an important job while we draft new distinctness, uniformity and stability (DUS) test guidelines. Grading criteria should be adjusted because of the effect of year and site; it is also a key task to establish applicable criteria in the DUS test. Excellent criteria will improve the accuracy of the DUS evaluation. In this study, we analyzed the variability and distribution patterns of nine quantitative characteristics of 251 anthurium varieties. Three methods were used to establish the grade criteria: the two standard deviation methods, the two LSD0.05 methods and the multiple comparison method. The results showed that the coefficient of variation within varieties varied from 6.96% to 10.11%. The quantitative characteristics observed in this study did not follow a normal distribution, except spadix thickness at the middle and spathe size. In most characteristics, the standard deviations and LSD0.05 were similar, except for spathe size. The state interval set by multiple comparison methods for every characteristic was variable, and its mean was about 1.25 times that of the other two methods. The process of establishing grading criteria using the multiple comparison method was simpler, and the criteria were more accurate, with a lower error rate.

Abstract Background Cryopreservation is the best way for long-term in vitro preservation of plant germplasm resources. The preliminary studies found that reactive oxygen species (ROS) induced oxidative stress and ice-induced membrane damage are the fundamental causes of cell death in cryopreserved samples. How to improve plant cryopreservation survival rate is an important scientific issue in the cryobiology field. Results This study found that the survival rate was significantly improved by adding single-wall carbon nanotubes (SWCNTs) to plant vitrification solution (PVS) in cryopreservation of Agapanthus praecox embryogenic callus (EC), and analyzed the oxidative response of cells during the control and SWCNTs-added cryopreservation protocol. The SWCNTs entered EC at the step of dehydration and mainly located around the cell wall and in the vesicles, and most of SWCNTs moved out of EC during the dilution step. Combination with physiological index and gene quantitative expression results, SWCNTs affect the ROS signal transduction and antioxidant system response during plant cryopreservation. The EC treated by SWCNTs had higher antioxidant levels, like POD, CAT, and GSH than the control group EC. The EC mainly depended on the AsA-GSH and GPX cycle to scavenge H2O2 in the control cryopreservation, but depended on CAT in the SWCNTs-added cryopreservation which lead to low levels of H2O2 and MDA. The elevated antioxidant level in dehydration by adding SWCNTs enhanced cells resistance to injury during cryopreservation. The ROS signals of EC were balanced and stable in the SWCNTs-added cryopreservation. Conclusions The SWCNTs regulated oxidative stress responses of EC during the process and controlled oxidative damages by the maintenance of ROS homeostasis to achieve a high survival rate after cryopreservation. This study is the first to systematically describe the role of carbon nanomaterial in the regulation of plant oxidative stress response, and provided a novel insight into the application of nanomaterials in the field of cryobiology.

Abstract Background Adnexal torsion during pregnancy is a gynecological emergency. Delayed diagnosis and treatment can cause ovarian necrosis and fetal loss. This study assessed the clinical characteristics, treatment and outcomes of adnexal torsion in pregnant women. Methods A retrospective study was conducted at a tertiary center between January 2008 and January 2018. Eighty-two pregnant women with surgically confirmed adnexal torsion were included. The clinical characteristics, ultrasound data, surgical interventions and pregnancy outcomes were analyzed. Results The median age of the patients was 28 (range, 18–38) years. The median gestational age was 11 (range, 6–31) weeks: 53 (64.6%) were in the first trimester, 21 (25.6%) were in the second trimester, and 8 (9.8%) were in the third trimester. The most common symptoms and signs were sudden pelvic pain (100%) and adnexal or pelvic masses (97.6%), followed by nausea and vomiting (61%). The Doppler blood flow signal disappeared in 62.5% of the patients. Sixty-three (76.8%) patients underwent laparoscopy, and 29 (24.2%) underwent laparotomy. The median gestational age in patients undergoing laparotomy was higher than that in those undergoing laparoscopy (26 weeks vs 10 weeks, p

Abstract Background Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare congenital disease characterized by uterovaginal agenesis. The diagnosis of MRKH syndrome generally leads to considerable emotional burdens on patients. However, studies focusing on the psychological influence on patients are limited and of unsatisfactory quality. The aim of this study was to investigate the prevalence of depressive symptoms in Chinese patients with MRKH syndrome and to identify the factors associated with depressive symptoms. We recruited 141 patients with MRKH syndrome and 178 age-matched healthy women as control group in this cross-sectional study. Depressive symptoms were assessed by the Patient Health Questionnaire-9 (PHQ-9). Other parameters such as sociodemographic characteristics, treatment histories, personality traits, and attitudes toward femininity and offspring, were also gathered in the self-administered questionnaire. Results The PHQ-9 score was significantly higher in MRKH patient group than the age-matched control group (7.0 (4.5–11.0) vs. 6.0 (3.0–9.0)), median and IQRs) (P = 0.015). A total of 75.2% of MRKH patients suffered from depressive symptoms, and 34.0% reached a moderate to severe level, while the proportion in the control group was 61.2 and 24.2% respectively. Compared with other age groups, patients in their 20s scored higher on the PHQ-9. Patients with higher neuroticism levels in personality traits (OR 1.19 95% CI 1.11–1.28), negative self-evaluation of femininity (OR 3.964, 95% CI 1.371–11.464) and sexual dysfunction (OR 4.81 95% CI 1.24–18.72) (compared with those having no sexual activity) were more likely to exhibit depressive symptoms. Conclusions Three-quarters of MRKH patients show depressive symptoms, and one-third of these individuals are even at risk for depressive disorders. Therefore, depressive symptom screening and proper psychotherapy in MRKH patients are of great importance.

Abstract. Background:. As a congenital malformation that results in infertility and an inability to have vaginal intercourse, Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome places a considerable psychological burden on patients, which results in anxiety symptoms. However, only single case studies or a few small to medium-sized cross-sectional studies were identified to focus on anxiety symptoms in MRKH patients. Thus, the aim of this study was to explore the status of anxiety symptoms and the related factors in patients with MRKH syndrome. Methods:. This cross-sectional study involving 141 patients with MRKH syndrome and 178 healthy women was conducted from January 2018 to December 2018. All participants were required to complete a demographic questionnaire and the Generalized Anxiety Disorder 7-item scale (GAD-7), Patient Health Questionnaire-9, Eysenck Personality Questionnaire-Revised, Short Scale for Chinese, and Chinese Version of the Female Sexual Function Index. The main outcome was the anxiety symptoms measured by the GAD-7. Main outcome was compared between the MRKH syndrome group and the healthy control group. Then, we explored the related factors by comparing patients with and without anxiety symptoms. Results:. Of the respondents, 24.1% experienced moderate to severe anxiety symptoms. Patients with MRKH syndrome manifested more severe anxiety symptoms than healthy women. Negative self-evaluation of femininity (odds ratio [OR] 2.706, 95% confidence interval [CI] 1.010–7.247), neurotic personality traits (OR 1.100, 95% CI 1.029–1.175), and coexisting depressive symptoms (OR 4.422, 95% CI 1.498–13.049) were more prevalent in anxious patients. Conclusion:. The findings stress the importance of anxiety symptom screening in MRKH patients and identify patients at risk of anxiety symptoms, providing a possible basis for future intervention.

Huangqin is the dried root of Scutellaria baicalensis Georgi, which has been widely utilized for heat-clearing (Qingre) and dewetting (Zaoshi), heat-killed (Xiehuo) and detoxifying (Jiedu) in the concept of Traditional Chinese Medicine and is used for treating inflammation and cancer in clinical formulas. Neobaicalein (NEO) is of flavonoid isolated from Huangqin and has been reported to possess prominent anti-inflammatory effects in published work. Th17/Treg balance shift to Th17 cells is an essential reason for autoimmune inflammatory diseases. However, the role NEO plays in Th17 and Treg and the underlying mechanism has not been elucidated yet. Network pharmacology-based study revealed that NEO predominantly regulated IL-17 signaling pathway. Moreover, our result shown that NEO (3–30 μmol/L) down-regulated Th17 differentiation and cellular supernatant and intracellular IL-17A level and tumor necrosis factor α production in a concentration-dependent manner. The further mechanism research revealed that NEO also specifically inhibited phosphorylation of STAT3(Tyr725) and STAT4 (Y693) without influence on activation of STAT5 and STAT6 in splenocytes. Immunofluorescence results illuminated that NEO effectively blocked STAT3 translocated into nucleus. Interestingly, NEO at appreciated dose could only inhibit Th17 cell differentiation and have no effect on Treg differentiation. The present study revealed that NEO effectively inhibited Th17 cell differentiation through specifically blocking the activation of STAT3 signaling without inactivation of STAT5 and STAT6. Additional inhibitory effect on activation of STAT4 by NEO also suggested the potential for antagonism against Th1 differentiation. All work suggested that NEO may be a potential candidate for immunoregulation and treating autoimmune inflammatory diseases through inhibiting immune cell viability and T cell differentiation.

The accuracy of the simulation model has a profound impact on the optimal operation of the energy hubs (EHs). However, in many articles, the constant model of the efficiency of equipment is adopted to formulate the operation system, which would probably lead to a simplification of the simulation models. But, EHs are typically operated under off-design condition due to the fluctuations in cooling, heating, electricity requirement. Moreover, even though the off-design characteristics are considered, few studies have suggested comparing the differences between those two models by considering the operation cost. In order to assess the effect of the off-design characteristics of EH on the optimal operation accuracy in this paper, two test cases are performed on the fixed and variable load conditions, respectively. In addition, the individual effect of off-design characteristics of each equipment on the optimal operation cost of the EH is also investigated through four optimization runs. It is worth mentioning that the optimal operation problem of the EH considering the off-design characteristics and on-off status of the equipment is a mixed integer non-linear programming problem (MINLP). By testing the design and off-design models on the two cases, the results of simulation demonstrate that the optimal operation cost for the off-design model is larger than that for the design model. Nonetheless, in the aspect of the authenticity of the system operation strategy, the off-design model performs better than the design model. Furthermore, a larger relative error of the system operation cost between the two models can be observed when the EH is operated under a relatively lower load condition, revealing that the influence of off-design characteristic on the optimal operation of EHs is too significant to be neglected.

Currently, most antioxidants do not show any favorable clinical outcomes in reducing myocardial ischemia-reperfusion (I/R) injury, suggesting an urgent need for exploring a new regulator of redox homeostasis in I/R hearts. Here, using heart-specific transgenic (TG) and knockdown (KD) mouse models, tumor susceptibility gene 101 (Tsg101) is defined as a novel cardiac-protector against I/R-triggered oxidative stress. RNA sequencing and bioinformatics data surprisingly reveal that most upregulated genes in Tsg101-TG hearts are transcribed by Nrf2. Accordingly, pharmacological inhibition of Nrf2 offsets Tsg101-elicited cardio-protection. Mechanistically, Tsg101 interacts with SQSTM1/p62 through its PRR domain, and promotes p62 aggregation, leading to recruitment of Keap1 for degradation by autophagosomes and release of Nrf2 to the nucleus. Furthermore, knockout of p62 abrogates Tsg101-induced cardio-protective effects during I/R. Hence, our findings uncover a previously unrecognized role of Tsg101 in the regulation of p62/Keap1/Nrf2 signaling cascades and provide a new strategy for the treatment of ischemic heart disease.

Loeys–Dietz syndrome (LDS) is a rare connective tissue genetic disorder that is caused by a pathogenic variant in genes of transforming growth factor (TGF) beta receptor 1 (TGFBR1), TGFBR2, mothers against decapentaplegic homolog 2 (SMAD2), SMAD3, TGFB2, or TGFB3. It is characterized by aggressive vascular pathology, aneurysms, arterial tortuosity, bifid uvula, hypertelorism, and cleft palate. Here we present a 42-year-old female patient with LDS. The patient underwent rapidly progressing artery aneurysms and life-threatening aortic dissection. Spontaneous fracture of the first metatarsal bone was noted in her medical record. Physical examination revealed a delayed wound healing on her left abdomen. Considering these clinical manifestations, we speculated that there was a genetic defect in the connective tissue, which provides strength and flexibility to structures such as bones, skins, ligaments, and blood vessels. Thus, whole exome sequencing (WES) was performed on the proband and revealed a heterozygous missense pathogenic variant (c.1613T > C/p.Val538Ala) in TGFBR2, which was a de novo variant in the proband as confirmed by the segregation analysis in parental samples. Although this variant was discovered and associated with the phenotype of LDS previously, the pathogenicity of the variant had not been confirmed by cellular functional assay yet. To further validate the effects of the variant in vitro, we assessed the canonical TGF-β signaling pathway in mutant cells. Our results showed that the p.Val538Ala variant significantly decreased TGF-β-induced gene transcription and the phosphorylation of Smad2, which were consistent with other pathogenic variants of TGFBR2. In conclusion, this study demonstrates that the p.Val538Ala pathogenic variant in TGFBR2 leads to aberrant TGF-β signaling and LDS in this patient.

Abstract Background Ovarian granulosa cell tumors (GCTs) are the most common type of potentially malignant ovarian sex cord-stromal tumor. GCTs often produce estrogen and/or progesterone; consequently, symptoms related to hyperestrogenism are common at diagnosis. Nonspecific symptoms or signs associated with this neoplasm include amenorrhea and changes in various sex hormone levels, which can be hard to diagnose or explain. The aims of this report were to describe a case of GCT with rare presentations and to review the pertinent literature. Case presentation A 33-year-old woman presented with secondary amenorrhea and elevated LH with normal FSH and low estradiol levels. Laparoscopy revealed an ovarian GCT, and the patient underwent left adnexectomy and platinum-based chemotherapy. Removal of the ovarian GCT resulted in the normalization of LH levels and a return to spontaneous menses. Conclusions The mechanisms responsible for elevations in serum LH due to GCTs require further investigation. However, addressing the patient’s clinical problems remains the most important treatment consideration.

Background: Cross-reactivity between pollen and plant foods results in low specificity of food-IgE and skin prick testing, which may cause over-diagnosis. A test that can accurately diagnose pollen-related food allergy and identify patients at risk of developing severe reactions is needed. This study evaluates basophil CD63 expression as a biomarker for diagnosis and predicting severity of mugwort pollen-related peach allergy. Methods: Based on their allergic reactions to peach, an oral allergy symptom group (OAS, n ​= ​15), a systemic reaction group (SR, n ​= ​23), a peach-sensitized but tolerant group (PST, n ​= ​21) and a non-peach-sensitized nonallergic group (NSE, n ​= ​10) were identified among mugwort pollen allergic patients. Measurements of specific IgE to peach and its components, and basophil activation test (BAT) were performed. Results: Upon stimulation with peach extract, BAT in peach-allergic patients (OAS and SR groups) showed a significant dose-dependent upregulation of CD63 compared with PST patients, but showed no difference between SR and OAS groups. BAT to Pru p 3 could discriminate not only between sensitization and clinical allergy, but also between OAS and systemic reactions. BAT to Pru p 3 revealed 92% sensitivity, 95% specificity, 92% positive predictive value, and 92% negative predictive value. Receiver operating characteristic curves showed that BAT to Pru p 3 had the largest area under the curve. Conclusions: In the diagnosis of mugwort pollen-related peach allergy, BAT to Pru p 3 is superior to testing for IgE specific for peach and its components. Additionally, basophil activation can predict clinical severity. Keywords: Basophil activation test, Peach extract, Pru p 3, Mugwort pollen allergy, Peach allergy

Background: Tetrahydrocurcumin (THC), an active metabolite of curcumin, has been reported to have similar biological effects to curcumin, but the mechanism of the antitumor activity of THC is still unclear. Methods: The present study was to investigate the antitumor effects and mechanism of THC in human breast cancer MCF-7 cells using the methods of MTT assay, LDH assay, flow cytometry analysis, and western blot assay. Results: THC was found to have markedly cytotoxic effect and antiproliferative activity against MCF-7 cells in a dose-dependent manner with the IC50 for 24 h of 107.8 μM. Flow cytometry analysis revealed that THC mediated the cell-cycle arrest at G0/G1 phase, and 32.8% of MCF-7 cells entered the early phase of apoptosis at 100 μM for 24 h. THC also dose-dependently led to apoptosis in MCF-7 cells via the mitochondrial pathway, as evidenced by the activation of caspase-3 and caspase-9, the elevation of intracellular ROS, a decrease in Bcl-2 and PARP expression, and an increase in Bax expression. Meanwhile, cytochrome C was released to cytosol and the loss of mitochondria membrane potential (Δψm) was observed after THC treatment. Conclusion: THC is an excellent source of chemopreventive agents in the treatment of breast cancer and has excellent potential to be explored as antitumor precursor compound.

Cardiac cells can adapt to pathological stress-induced energy crisis by shifting from fatty acid oxidation to glycolysis. However, the use of glucose-insulin-potassium (GIK) solution in patients undergoing cardiac surgery does not alleviate ischemia/reperfusion (I/R)-induced energy shortage. This indicates that insulin-mediated translocation of glucose transporter-4 (Glut-4) is impaired in ischemic hearts. Indeed, cardiac myocytes contain two intracellular populations of Glut-4: an insulin-dependent non-endosomal pool (also referred to as Glut-4 storage vesicles, GSVs) and an insulin-independent endosomal pool. Tumor susceptibility gene 101 (Tsg101) has been implicated in the endosomal recycling of membrane proteins. In this study, we aimed to examine whether Tsg101 regulated the sorting and re-distribution of Glut-4 to the sarcolemma membrane of cardiomyocytes under basal and ischemic conditions, using gain- and loss-of-function approaches. Forced overexpression of Tsg101 in mouse hearts and isolated cardiomyocytes could promote Glut-4 re-distribution to the sarcolemma, leading to enhanced glucose entry and adenosine triphosphate (ATP) generation in I/R hearts which in turn, attenuation of I/R-induced cardiac dysfunction. Conversely, knockdown of Tsg101 in cardiac myocytes exhibited opposite effects. Mechanistically, we identified that Tsg101 could interact and co-localize with Glut-4 in the sarcolemma membrane of cardiomyocytes. Our findings define Tsg101 as a novel regulator of cardiac Glut-4 trafficking, which may provide a new therapeutic strategy for the treatment of ischemic heart disease.

In this paper, the mechanical characteristics of stabilizing piles embedded in layered bedrocks are studied both experimentally and numerically. The influence of soft and hard interbedded layers in the structure of the bedrock on the mechanical characteristics of stabilizing piles is particularly investigated. The discrete element method is used to numerically investigate the response of the stabilizing piles embedded in composite and inclined bedrocks. The simulation results and comparison with experimental data are presented to demonstrate the effectiveness and accuracy of the discrete element model. As the dip angle of the soft/hard interbedded bedrock layers increases from 0° to 45°, it is observed that the displacement of the embedded section of the stabilizing pile increases and reaches the maximum displacement at 45°. In the range of 45° to 75°, the influence of the dip angle of the layered bedrock on the displacement of the embedded section of the pile is gradually reduced.

Intrathoracic endotracheal metastasis from a very distant site is extremely rare. We report the first case of such a disease in a 68-year-old man with nasopharyngeal carcinoma who presented with a cough and hemoptysis 34 months after finishing radiotherapy. Prior to tracheal metastasis, he developed a solitary metastasis in the lung and underwent chemotherapy followed by radiotherapy. Computed tomography showed the presence of an enlarged lymph node in the para-aortic arch. Fiberoptic bronchoscopy revealed an endotracheal tumor 1 cm above the carina. Histological and immunohistochemical analyses confirmed its nasopharyngeal origin. He was treated with conventional radiotherapy and three-dimensional conformal radiotherapy; complete tumor remission was achieved. He died of nonmalignant disease with no signs of tumor recurrence 2 years after treatment completion. Radiotherapy may be an appropriate management approach to achieve long-term tumor control for this disease.

The simulation model is one of the key points affecting the optimal planning and operation of energy hubs (EHs). Since treating the efficiencies of generation units as constants would significantly simplify the calculation, only a simplified model is investigated in most research works. In this paper, aiming at optimizing the capacity configuration of an EH, we present a part-load characteristics-based (PLCB) model, in which the efficiencies of generation units will change with the fluctuating load. Based on the PLCB model, the accuracy of the EH model can be improved. Furthermore, a two-stage planning method is proposed to solve the optimal capacity configuration problem of the EH. Group Search Optimizer (GSO) is used to determine the optimal size in the first stage, and a mathematical programming method is applied to obtain the optimal operation of the EH in the second stage. Comparative studies using the PLCB model and the simplified model are performed to examine the impacts of equipment part-load characteristics on the sizing results. Simulation results indicate that the proposed model appears to have a better economic performance than the simplified model.

BACKGROUND: Transforming growth factor type-β (TGF-β)/Smad pathway plays an essential role in vascular fibrosis. Reactive oxygen species (ROS) generation also mediates TGF-β signaling-induced vascular fibrosis, suggesting that some sort of interaction exists between Smad and redox pathways. However, the underlying molecular mechanism is largely unknown. This study aims to investigate the influence of poly(ADP-ribose) polymerase 1 (PARP1), a downstream effector of ROS, on TGF-β signaling transduction through Smad3 pathway in rat vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: TGF-β1 treatment promoted PARP1 activation through induction of ROS generation in rat VSMCs. TGF-β1-induced phosphorylation and nuclear accumulation of Smad3 was prevented by treatment of cells with PARP inhibitor, 3-aminobenzamide (3AB) or N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-2-(N,N-dimethylamino)acetami (PJ34), or PARP1 siRNA. TGF-β1 treatment promoted poly(ADP-ribosy)lation of Smad3 via activation of PARP1 in the nucleus. Poly(ADP-ribosy)lation enhanced Smad-Smad binding element (SBE) complex formation in nuclear extracts and increased DNA binding activity of Smad3. Pretreatment with 3AB, PJ34, or PARP1 siRNA prevented TGF-β1-induced Smad3 transactivation and expression of Smad3 target genes, including collagen Iα1, collagen IIIα1 and tissue inhibitor of metalloproteinase 1, in rat VSMCs. CONCLUSIONS: PARP1 is indispensable for TGF-β1 induced Smad3 activation in rat VSMCs. Targeting PARP1 may be a promising therapeutic approach against vascular diseases induced by dysregulation of TGF-β/Smad3 pathway.

Aldehyde dehydrogenase isoform 1 (ALDH1) has been proved useful for the identification of cancer stem cells. However, our knowledge of the expression and activity of ALDH1 in common epithelial cancers and their corresponding normal tissues is still largely absent. Therefore, we characterized ALDH1 expression in 24 types of normal tissues and a large collection of epithelial tumor specimens (six cancer types, n = 792) by immunohistochemical staining. Using the ALDEFUOR assay, ALDH1 activity was also examined in 16 primary tumor specimens and 43 established epithelial cancer cell lines. In addition, an ovarian cancer transgenic mouse model and 7 murine ovarian cancer cell lines were analyzed. We found that the expression levels and patterns of ALDH1 in epithelial cancers are remarkably distinct, and they correlate with their corresponding normal tissues. ALDH1 protein expression levels are positively correlated with ALDH1 enzymatic activity measured by ALDEFLUOR assay. Long-term in vitro culture doesn't significantly affect ALDH1 activity in epithelial tumor cells. Consistent with research on other cancers, we found that high ALDH1 expression is significantly associated with poor clinical outcomes in serous ovarian cancer patients (n = 439, p = 0.0036). Finally, ALDH(br) tumor cells exhibit cancer stem cell properties and are resistant to chemotherapy. As a novel cancer stem cell marker, ALDH1 can be used for tumors whose corresponding normal tissues express ALDH1 in relatively restricted or limited levels such as breast, lung, ovarian or colon cancer.

The Phosphatidylinositol 3'-kinase is a key regulator in various cancer-associated signal transduction pathways. Genetic alterations of its catalytic subunit alpha, PIK3CA, have been identified in ovarian cancer. Our in vivo data suggests that PIK3CA activation is one of the early genetic events in ovarian cancer. However, its role in malignant transformation of ovarian surface epithelium (OSE) is largely unclear.Using the Müllerian inhibiting substance type II receptor (MISIIR) promoter, we generated transgenic mice that expressed activated PIK3CA in the Müllerian epithelium. Overexpression of PIK3CA in OSE induced remarkable hyperplasia, but was not able to malignantly transform OSE in vivo. The consistent result was also observed in primary cultured OSEs. Although enforced expression of PIK3CA could not induce OSE anchorage-independent growth, it significantly increased anchorage-independent growth of OSE transformed by mutant K-ras.While PIK3CA activation may not be able to initiate OSE transformation, we conclude that activation of PIK3CA may be an important molecular event contributing to the maintenance of OSE transformation initiated by oncogenes such as K-ras.