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Abstract Background Gorham-Stout disease (GSD) is a very rare disorder characterized by massive osteolysis of poorly understood aetiology. The association between GSD involving the skull base and cerebrospinal fluid (CSF) leakage has been reported in the literature. However, few cases of CSF leakage and Chiari-like tonsillar herniation in GSD involving the spine have been reported. Case presentation We present the case of a 20-year-old man with GSD involving the thoracic and lumbar spine, which caused CSF leakage and Chiari-like tonsillar herniation. The patient underwent four spinal surgeries for osteolytic lesions of the spine over a 10-year period. Here, we discuss the possible aetiology of the development of CSF leakage. Epidural blood patch (EBP) was performed at the T11-T12 level to repair the CSF leakage. After EBP treatment, rebound intracranial hypertension (RIH) developed, and tonsillar herniation disappeared 2 months later. Conclusions GSD involving the spine with CSF leakage and Chiari-like tonsillar herniation is relatively rare. For patients who have undergone multiple spinal surgeries, minimally invasive treatment is an alternative treatment for CSF leakage. EBP can repair CSF leakage secondary to GSD and improve chronic brain sagging, with reversibility of Chiari-like malformations.

Battery lifetime prediction is critical to successfully introducing new products to the market, and a long testing time will affect the promotion of the product. In this paper, the ambient temperature (25–45 ℃), charge cut-off voltage (CCOV) (4.2–4.4 V), and discharge rate (0.5–2C) to performance degradation of LiMn0.6Fe0.4PO4 and LiNi0.5Co0.2Mn0.3O2 (LMFP/NCM) composite cathode batteries are revealed by the accelerated life test. The results indicated that the CCOV in the range of 4.3 - 4.4 V was significant. The discharge rate effect was less affected (no more than 2C). Furthermore, single stress factor and multi-stress factor models consisting of temperature, discharge rate, CCOV, and state of health (SOH) for cycle life prediction are developed based on the revised Arrhenius equation and the inverse power law equation. It is shown that the proposed life model can accurately predict battery capacity degradation, and the estimation error is less than 2%. The developed model helps to predict the lifetime of the battery under different SOH and optimize the operation conditions of the battery. [ABSTRACT FROM AUTHOR]

Obesity is acknowledged as a significant risk factor for various metabolic diseases, and the inhibition of human pancreatic lipase (hPL) can impede lipid digestion and absorption, thereby offering potential benefits for obesity treatment. Anthraquinones is a kind of natural and synthetic compounds with wide application. In this study, the inhibitory effects of 31 anthraquinones on hPL were evaluated. The data shows that AQ7, AQ26, and AQ27 demonstrated significant inhibitory activity against hPL, and exhibited selectivity towards other known serine hydrolases. Then the structure-activity relationship between anthraquinones and hPL was further analysed. AQ7 was found to be a mixed inhibition of hPL through inhibition kinetics, while AQ26 and AQ27 were effective non-competitive inhibition of hPL. Molecular docking data revealed that AQ7, AQ26, and AQ27 all could associate with the site of hPL. Developing hPL inhibitors for obesity prevention and treatment could be simplified with this novel and promising lead compound. [ABSTRACT FROM AUTHOR]

Plants have the potency to regenerate adventitious roots from aerial organs after detachment. In Arabidopsis thaliana, de novo root regeneration (DNRR) from leaf explants is triggered by wounding signaling that rapidly induces the expression of the ETHYLENE RESPONSE FACTOR (ERF) transcription factors ERF109 and ABR1 (ERF111). In turn, the ERFs promote the expression of ASA1, an essential enzyme of auxin biosynthesis, which contributes to rooting by providing high levels of auxin near the wounding side of the leaf. Here, we show that the loss of the epigenetic regulator ULTRAPETALA1 (ULT1), which interacts with Polycomb and Trithorax Group proteins, accelerates and reinforces adventitious root formation. Expression of ERF109 and ASA1 was increased in ult1 mutants, whereas ABR1 was not significantly changed. Cultivation of explants on media with exogenous auxin equates adventitious root formation in wild-type with ult1 mutants, suggesting that ULT1 negatively regulates DNRR by suppressing auxin biosynthesis. Based on these findings, we propose that ULT1 is involved in a novel mechanism that prevents overproliferation of adventitious roots during DNRR.

β-Ga2O3, with excellent bandgap, breakdown field, and thermal stability properties, is considered to be one of the most promising candidates for power devices including field-effect transistors (FETs) and for other applications such as Schottky barrier diodes (SBDs) and solar-blind ultraviolet photodetectors. Ohmic contact is one of the key steps in the β-Ga2O3 device fabrication process for power applications. Ohmic contact techniques have been developed in recent years, and they are summarized in this review. First, the basic theory of metal–semiconductor contact is introduced. After that, the representative literature related to Ohmic contact with β-Ga2O3 is summarized and analyzed, including the electrical properties, interface microstructure, Ohmic contact formation mechanism, and contact reliability. In addition, the promising alternative schemes, including novel annealing techniques and Au-free contact materials, which are compatible with the CMOS process, are discussed. This review will help our theoretical understanding of Ohmic contact in β-Ga2O3 devices as well as the development trends of Ohmic contact schemes.

BackgroundMental health disorders in systemic lupus erythematosus (SLE) are gradually getting recognized; however, less is known regarding the actual structure and compositional alterations in gut microbiome and metabolism and the mechanisms of how they affect depression development in SLE patients.MethodsTwenty-one SLE patients with depression (SLE-d), 17 SLE patients without depression (SLE-nd), and 32 healthy controls (HC) were included in this study. Fecal samples were collected for 16S rRNA gene sequencing and ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) based metabolomics.ResultsThe structure of gut microbiome in the SLE-d group changed compared with that in the other two groups. The microbiome composition of SLE-d group showed decreased species richness indices, characterized by low ACE and Chao1 indices, a decrease in the ratio of phylum Firmicutes to Bacteroidetes, genus Faecalibacterium and Roseburia. A downregulation of the metabolite fexofenadine involved in bile secretion was positively correlated with the genus Faecalibacterium, Subdoligranulum and Agathobacter. Compared with the SLE-nd group, the SLE-d group had elevated serum levels of IL-2 and IL-6 and decreased BDNF. Interestingly, abundance of the genus Faecalibacterium and Roseburia was negatively correlated with IL-6, abundance of the genus Roseburia was negatively correlated with IL-2, and abundance of the genus Bacteroides was positively correlated with IL-2.ConclusionThis study identified specific fecal microbes and their metabolites that may participate in the development of SLE-d. Our findings provide a new perspective for improving depression in SLE patients by regulating the gut–brain axis.

Pluripotent stem-cells are slowly dividing cells giving rise to daughter cells that can either differentiate to new tissues and organs, or remain stem-cells. In plants, stem-cells are located in specific niches of the shoot and root apical meristems (SAMs and RAMs). After ablation of stem-cell niches, pluripotent meristematic cells can establish new stem-cells, whereas the removal of the whole meristem destructs the regeneration process. In tissue cultures, after detached plant organs are transferred to rooting or callus induction medium (G5 or CIM), vasculature-associated pluripotent cells (VPCs) immediately start proliferation to form adventitious roots or callus, respectively, while other cell types of the organ explants basically play no part in the process. Hence, in contrast to the widely-held assumption that all plant cells have the ability to reproduce a complete organism, only few cell types are pluripotent in practice, raising the question how pluripotent stem-cells differ from differentiated cells. It is now clear that, in addition to gene regulatory networks of pluripotency factors and phytohormone signaling, epigenetics play a crucial role in initiation, maintenance and determination of plant stem-cells. Although, more and more epigenetic regulators have been shown to control plant stem-cell fate, only a few studies demonstrate how they are recruited and how they change the chromatin structure and transcriptional regulation of pluripotency factors. Here, we highlight recent breakthroughs but also revisited classical studies of epigenetic regulation and chromatin dynamics of plant stem-cells and their pluripotent precursor-cells, and point out open questions and future directions.

IntroductionImmune therapy has ushered in a new era of tumor treatment, at the expense of immune-related adverse events, including rare but fatal adverse cardiovascular events, such as myocarditis. Steroids remain the cornerstone of therapy for immune-related myocarditis, with no clear consensus on additional immunosuppressive treatment for steroid-refractory cases yet.Case reportHere, we report a patient with stage IV nasopharyngeal carcinoma who developed immune-related myocarditis in the fourth course of therapy with immune checkpoint inhibitors. The patient presented with precordial discomfort with elevation of cardiac enzymes and interleukin-6, atypical electrocardiographic abnormalities, and reduced left ventricular ejection fraction. Coronary computed tomography angiography excluded the possibility of acute coronary syndrome. The therapy with tofacitinib targeting the Janus kinase-signal transducer and activator of transcription signal pathway was successfully conducted, since there was no significant improvement in troponin under high-dose steroid and intravenous immunoglobulin treatment. The patient recovered without major adverse cardiac events during hospitalization.DiscussionThe safety and efficacy of tofacitinib in a patient with steroid-refractory immune-related myocarditis were investigated, hoping to provide a basis for prospective therapeutic strategies. Tofacitinib led to remarkable remissions in primary autoimmune disease by blocking the inflammatory cascade, indicating its potential therapeutic use in immune-related adverse events.

BackgroundWe evaluated the cost-effectiveness of the screening in mainland China for Alzheimer’s disease (AD) patients aged over 60.MethodsIndividuals in mainland China, received an initial screening by questionnaire on mental state, and those with scores deemed suspicious for AD were referred to diagnostic tests. A 9-state Markov model was developed to simulate the disease progression of a cohort of 100,000 subjects aging from 60 to 80. In addition, several scenarios were analyzed to assess the robustness under different screening frequency, starting age, the duration of drug effects, and the health status of subjects.ResultsThe ICER of AD screening was 26413.77 USD per QALY [quality-adjusted life-year (QALY)] compared with no screening. The number of deaths and severe AD cases who did not receive treatment averted by screening accounted for 0.076 and 0.006% of the total population, respectively, and the net monetary benefit was 128.29 USD per capita. Under the thresholds of one and three times the gross domestic product per capita, the probability of screening being cost-effective was approximately 18 and 77%, respectively. The ICER decreased to 18132.96USD per QALY when the drug effect was prolonged, and increased when the frequency of screening was increased, the starting age was postponed, and patients suffering from comorbidities were more. However, the number of severe AD cases and deaths declined when the screening frequency increased.ConclusionScreening for AD in individuals over 60 can reduce the numbers of severe AD cases and deaths and may be cost-effective, depending on factors such as screening frequency, starting age of screening, and duration of drug effects. Additionally, mild cognitive impairment (MCI) is an important stage at which the burden of progression to AD may be reduced and the cost-effectiveness of screening may be improved.

The identification of geochemical anomalies in oil and gas indicators is a fundamental task in oil and gas exploration, as the process of oil and gas accumulation is a low probability event. Machine learning algorithms for anomaly detection are applicable to the identification of oil and gas geochemical anomalies related to oil and gas accumulation. However, when using oil and gas indicators for anomaly detection, the diversity of these indicators often leads to the influence of the indicator redundancy on the identification of such features. Therefore, it is particularly important to select appropriate oil and gas indicators for anomaly detection. In this study, a hybrid model combining unsupervised machine learning methods and singularity analysis methods was used to evaluate oil and gas indicator anomalies using geochemical data from the Taiwan Strait Basin. The models used in this study include the singularity index model, the principal component model combined with the singularity index model, and the cluster analysis combined with the principal component model and the singularity index model. PCA models can reduce the dimensions of the data and retain as much information as possible. CLA divides data samples into different groups, so that samples within the same group are more similar and samples between different groups are less similar. LSP is mainly used for measuring the setting and singular degree of local anomalies in multi-scale geochemistry, geophysics, and other types of local anomalies, and it has a unique advantage in extracting low and weak anomalies and nonlinear characteristics. The results of the study show that the results obtained using the CLA-PCA-LSP hybrid model are very similar to those obtained by performing PCA on the entire index and then calculating the singularity index. This also verifies that, for the study areas of the Jiulongjiang Depression and Jinjiang Depression, we can select oil and gas indicators that are favorable for exploration analysis, without including all indicators in the analysis scope, thereby improving the computational efficiency. The application of a singularity analysis method and generalized self-similarity principle in extracting the geochemical information of oil and gas indicators in the Taiwan Strait Basin highlights key technologies such as the identification of weak anomalies, decomposition of composite anomalies, and integration of spatial information. The combination anomalies delineated by the singularity analysis method and S-A method not only reflect the spatial relationship with known oil and gas reservoir distribution, but also show the multiple combination anomalies in unknown areas, providing favorable guidance for the next exploration direction in the Taiwan Strait Basin. [ABSTRACT FROM AUTHOR]

Background: Under the current pandemic of Corona Virus Disease 2019 (COVID-19), The relationship between fatigue and COVID-19 has been found. Infection with COVID-19 is associated with fatigue long after the acute phase of COVID-19. Understanding the association of thyroid hormones levels with post-COVID condition, such as fatigue, is necessary to improve quality of life. Methods: This population-based cohort study was conducted in Dalian, China, from December 2022, to March 2023, using a Yidu Core platform in the First Affiliated Hospital of Dalian Medical University, that integrates medical records, laboratory tests, and all diagnosis and treatment information based on patients in hospital. Eligible individuals were 40 patients with COVID-19, Divided them into fatigue group and non-fatigue group following up by telephone using the FS-14 scale after 6 months. The primary outcomes were the diagnoses of fatigue. The association between thyroid hormones levels and post-COVID condition, such as fatigue, was assessed using logistic regression analysis. Results: Compared with the non-fatigue group, the FT3 level in fatigue group was lower (p<0.05). FT3 was negatively correlated with fatigue after 6 months (OR 0.257, p<0.05). After adjusting for confounding factors such as age and gender, low FT3 was a risk factor for fatigue in patients with COVID-19, (OR 0.225, p<0.05). And the FT3 is less than 2.47 mol/L, it is the best critical value for predicting long-term fatigue, with a sensitivity of 92.3% and a specificity of 48.1%. Conclusions: Most people still have fatigue 6 months after COVID-19 infection. FT3 serves as the important index to predict fatigue in patients with COVID-19. it should be closely monitored during infection. [ABSTRACT FROM AUTHOR]

The thermal safety of lithium-ion batteries has garnered significant attention due to its pivotal role in the field of new energy. In this work, a three-dimensional electrochemical-thermal coupling model based on the P2D model was established for predicting the thermal performance. The charge-discharge and temperature rise experiments via 18650 cylindrical Li[Ni0.6Co0.2Mn0.2]O2 / graphite batteries are designed to confirm the rationality of the model. The simulation results show that the highest temperature of the battery surface during discharging at 1 C and 4 C are 42.85 °C and 61.25 °C, and the experimental results are 42.50 °C and 62.85 °C, respectively. The electrode heat generation mainly comes from the reaction heat of cathode and anode during 1 C charge process, the maximum power is 1.2 W and 0.6 W, respectively. In the discharge process, the cathode dominates the reaction contribution of 1.02 W and the reaction heat power from the anode is only 0.016 W. The capacity of heat dissipation can be increased by enhancing the convective heat transfer coefficient and air velocity within a reasonable range. The proposed electrochemical-thermal coupling model is valuable to evaluate the heat behavior and promote the battery development. [ABSTRACT FROM AUTHOR]

ObjectivesThe progressive impairment of β-cell function results in prolonged deterioration in patients with type 2 diabetes mellitus (T2DM). Interestingly, the finding on pancreatitis secondary to renal injury suggests that potential communication exists between kidney and pancreas. Therefore, we aimed to investigate cell division cycle 42 (Cdc42)-mediated podocyte apoptosis and its effect on insulin secretion in islet β-cells.MethodsType 2 diabetic nephropathy mouse models were established to identify the expression of Cdc42 in podocytes by immunohistochemistry. An in vitro co-culture of mouse podocyte MPC5 and β-TC6 cells was preliminarily established. Subsequently, podocyte apoptosis induced by high glucose and Cdc42 was detected by TUNEL staining and western blotting. In addition, the JNK pathway was examined to determine the mechanism of apoptosis in MPC5 cells. Finally, insulin secretion and expression in β-TC6 cells as well as malondialdehyde (MDA) and superoxide dismutase (SOD) levels in both cell types were examined after the regulation of Cdc42 in MPC5 cells.ResultsCdc42 was highly expressed in the podocytes of diabetic nephropathy mice. Exposure to 25 mM glucose for 48 h induced a significant upregulation of Cdc42, Bax, and cleaved caspase-3 as well as a decreased Bcl-2 expression. In addition, marked apoptosis of MPC5 cells was observed compared to normal glucose treatment. After transfection with Cdc42 plasmid, apoptosis of MPC5 cells was enhanced with an increased expression of p-JNK, whereas inhibition of Cdc42 significantly alleviated podocyte apoptosis accompanied by a downregulation of p-JNK. The glucose-stimulated insulin secretion level of β-TC6 cells decreased after the upregulation of Cdc42 in MPC5 cells. Immunofluorescence staining for insulin showed that co-culture with MPC5 cells carrying the Cdc42 plasmid significantly reduced insulin expression, whereas inhibition of Cdc42 in MPC5 cells alleviated the above-mentioned abnormality of β-TC6 cells. The expression of Cdc42 and p-p38 in β-TC6 cells increased following the upregulation of Cdc42 in MPC5 cells; this was concurrent with augmented MDA levels and decreased SOD activity. The opposite result was observed for Cdc42 knockdown in MPC5 cells.ConclusionsCdc42 in podocytes plays a crucial role in insulin secretion by β-cells, which may provide a new therapeutic target to prevent the vicious cycle of β-cell dysfunction in T2DM.

ObjectiveThis study aimed to evaluate the cost-effectiveness of the colorectal cancer screening in China, and that when the screening was implemented in a specific region.MethodsA 13-state Markov model was established to compare four screening protocols, including annual fecal immunochemical testing (FIT1), biennial fecal immunochemical testing (FIT2), electronic colonoscopy every 10 years (e-CSPY10), and electronic colonoscopy every 5 years (e-CSPY5), with no screening from the perspective of Chinese healthcare system. The model simulated the health states of a cohort of 100,000 average-risk individuals aging from 50 to 75. Additionally, scenarios including the implementation in a specific region, starting from 40, and incompletely successful treatment of cancer were also analyzed.ResultsAnnual and biennial FIT could save 8.13USD (US Dollar) and 44.96USD per person, and increase 0.0705QALYs (Quality-Adjusted Life Years) and 0.2341 QALYs compared with no screening, respectively. Annual FIT could decrease costs by 36.81USD per person and increase 0.1637 QALYs in comparison to biennial FIT. The results showed that both annual and biennial FIT for screening were dominant over no screening, and annual FIT was dominant over biennial FIT. The ICER (Incremental Cost-Effectiveness Ratio) for e-CSPY10 were 1183.51USD/QALY and 536.66USD/QALY compared with FIT1 and FIT2. The ICER for e-CSPY5 were 1158.16USD/QALY and 770.85USD/QALY compared with FIT1 and FIT2. And the ICER for e-CSPY5 relative to e-CSPY10 was 358.71USD/QALY. All the ICER values were lower than the economic threshold of 2021 Chinese GDP (Gross Domestic Product) per capita in 2021(12554.42USD).ConclusionsIt is worthwhile to popularize CRC screening in mainland China, as FIT always saving costs and colonoscopy is cost-effective. Regions with high income can take electronic colonoscopy every 10 years, or even every 5 years into consideration when determining the specific strategies.