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Background: Chronic myeloid leukemia (CML) is one of the most common adult leukemias. The considerable negative changes in its acute phase and the adverse drug effects could lead to poor prognosis. N6-methyladenine (m6A) modification plays an important regulatory role in physiological and pathological processes. KIAA1429 is an important m6A regulator, but the biological role of KIAA1429 in CML is still unclear. Methods: RT-qPCR and Western blot were used to analyze the differential expression of KIAA1429 in CML clinical samples and cell lines. CCK-8, EdU staining, flow cytometry, Transwellassay, cellular morphology evaluation, and liquid chromatography-mass spectrometry (LC-MS) were further implemented to assess the changes in the biological functions of CML cell lines with KIAA1429 knockdown or overexpression. In addition, subcutaneous tumorigenesis experiment in nude mice was performed for in vivo function assessment. The combination of MeRIP-seq and mRNA-seq predicted that RAB27B is a downstream target gene of KIAA1429. RIP-qPCR, RNA stability analysis, SELECT, and “rescue” experiments were then conducted to explore the mechanisms underlying the regulation of KIAA1429/m6A/YTHDF1 axis on RAB27B. Finally, the inhibitory effects of rucaparib on KIAA1429 and CML were explored in vitro and in vivo. Results: The m6A and KIAA1429 expression was significantly upregulated in patients with blast phase CML. KIAA1429 was found to regulate the total level of RNA m6A modification in the CML cells and to promote the malignant biological behaviors of CML cells, including proliferation, migration, and imatinib resistance. Inhibiting KIAA1429 in CML cells regulated the stability of RAB27B mRNA through the m6A/YTHDF1 axis, consequently inhibiting CML proliferation and drug efflux, and ultimately increasing cell sensitivity to imatinib. Rucaparib suppressed the expression of KIAA1429 and CML cell proliferation, and promoted cell apoptosis. The combined use of rucaparib and imatinib enhanced the sensitivity of CML cells to imatinib. Rucaparib inhibited the tumorigenesis capability of CML cells in vivo. Conclusions: Elevated KIAA1429 expression in the blast phase of CML enhanced the stability of RAB27B mRNA through the m6A/YTHDF1 axis to upregulate RAB27B expression, and thus promoting CML progression. Therefore, rucaparib exerts inhibitory effects on KIAA1429 expression and CML progression.

This work investigates the high-voltage linear multi-string LED driving scheme for three-phase AC power grids and confirms the superiority and practicality of this scheme in lighting applications for the first time. Three-phase AC power amplifies the excellent performance of linear multi-string LED driving systems in comparison to single-phase AC power. Based on the features of the rectified voltage waveform in the three-phase AC power supply, the LED distributions of the linear multi-string LED driving scheme were calculated with a unique optimization method to balance LED power and driving efficiency within ± 10% voltage fluctuations. And a double-string LED lighting system was constructed as a module prototype with the capability of scaling up. The experimental results exhibit high driving efficiency (~ 94% @380V line voltage), high power factor (~ 0.952), flicker-free, and high reliability at an extremely low cost (~$0.005/W).

This paper mainly focuses on the problems of attack detection and reconstruction of cyber physical systems (CPS) under dynamic load altering attacks (D-LAA). Taking the smart grid as an example, firstly, the power system subjected to the attack is modeled as a power CPS through system characteristics to provide conditions for attack detection. On this basis, we assume that two vulnerable loads are attacked simultaneously to investigate the impact of the attack on the system. Secondly, a robust sliding mode observer is designed to implement attack reconstruction with the residual signal generated by the observer. After that, an attack detection logic is applied to complete the attack detection by comparing the threshold with the residual. Finally, a three generators and six buses power system is given as an example to verify the feasibility of attack detection and reconstruction by using the real-time simulation platform built by StarSim and MT respectively. The simulation results are given in this paper.

Occupational health and safety are critical in promoting the wellness of organizations and employees. The COVID-19 pandemic is one of the most life-threatening viruses encountered in recent history, providing a unique opportunity for research to examine factors that drive employee safety behavior. Drawing from terror management theory, we propose and test a moderated mediation model using data collected from employees working during a peak of the pandemic. We identify two sources of influence - one external (i.e., media exposure), and one internal (i.e., HR practices) to the organization - that shape employees' mortality salience and safety behaviors. We find that COVID-19 HR practices significantly moderate the relationship between daily COVID-19 media exposure and mortality salience, with media exposure positively associated with mortality salience at lower levels of HR practices but its effects substituted by higher levels of HR practices. Moreover, our results also show that mortality salience spurs safety behaviors, with age moderating this relationship such that younger - but not older - employees are more likely to engage in safety behaviors due to mortality salience. Taken together, we offer theoretical implications for the safety behavior literature and practical implications for organizations faced with health crises or having employees who commonly work in hazardous conditions.

Cyclic AMP (cAMP) is a ubiquitous second messenger that transduces signals from cellular receptors to downstream effectors. Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, devotes a considerable amount of coding capacity to produce, sense, and degrade cAMP. Despite this fact, our understanding of how cAMP regulates Mtb physiology remains limited. Here, we took a genetic approach to investigate the function of the sole essential adenylate cyclase in Mtb H37Rv, Rv3645. We found that lack of rv3645 resulted in increased sensitivity to numerous antibiotics by a mechanism independent of substantial increases in envelope permeability. We made the unexpected observation that rv3645 is conditionally essential for Mtb growth only in the presence of long-chain fatty acids, a host-relevant carbon source. A suppressor screen further identified mutations in the atypical cAMP phosphodiesterase rv1339 that suppress both fatty-acid and drug sensitivity phenotypes in strains lacking rv3645. Using mass spectrometry, we found that Rv3645 is the dominant source of cAMP under standard laboratory growth conditions, that cAMP production is the essential function of Rv3645 in the presence of long-chain fatty acids, and that reduced levels of cAMP result in increased antibiotic susceptibility. Our work defines rv3645 and cAMP as central mediators of intrinsic multidrug resistance and fatty acid metabolism in Mtb and highlights the potential utility of small molecule modulators of cAMP signaling.

Ventricular arrhythmia is one of the main causes of sudden cardiac death, especially after myocardial ischemia. Previous studies have shown that Chai-Hu-San-Shen capsule (CHSSC) can reduce the incidence of ventricular arrhythmias following myocardial ischemia, however, the mechanisms of it are unclear. In present study, we explored the mechanism of CHSSC ameliorates ventricular arrhythmia following myocardial ischemia via inhibiting the CaMKII/FKBP12.6/RyR2/Ca

ImportanceHepatitis B surface antigen (HBsAg) reportedly increases the risk of distant metastasis among patients with nasopharyngeal carcinoma (NPC). However, the associated potential interaction and changes in hazard ratios (HRs) between HBsAg and different plasma Epstein-Barr (EBV) DNA levels are unknown. Moreover, the potential HBsAg-positive–associated NPC metastatic mechanism remains unclear.ObjectiveTo investigate the prognostic value and biological associations of HBsAg and plasma EBV DNA levels on distant metastasis in patients with NPC.Design, Setting, and ParticipantsRetrospective cohort study performed at Sun Yat-sen University Cancer Center between January 2010 and January 2013. A total of 792 patients with nonmetastatic NPC were enrolled. The median (range) follow-up time was 62.1 (1.4-83.4) months. Of these patients, 17.8% presented with HBsAg positivity. Cytological experiments were performed to evaluate the role of HBsAg in the invasion and migration of EBV-positive NPC cells. Data analysis was performed from July 2020 to April 2021.Main Outcomes and MeasuresThe primary end point was distant metastasis–free survival. Association rules were used to identify new rules related to distant metastasis. Interaction plots, univariate and multivariate Cox regression analyses, stratification analysis, and quantification using HRs were conducted. Additionally, cell migration and invasion assays, as well as Western blotting, were performed in the cytological validation.ResultsAmong the 792 patients, 576 (72.7%) were male, with a median (IQR) age of 45 (38-53) years. The HBsAg-positive group exhibited a significant interaction and increased risk of distant metastasis when plasma EBV DNA cutoff levels were 1.5 × 1000 copies/mL or greater. The HR was 9.16 (95% CI, 2.46-34.14) when the plasma EBV DNA load reached 6 × 1000 copies/mL, which was higher than that in patients with stage IV disease (HR, 2.01; 95% CI, 1.13-3.56; P = .02). In cytological experiments, HBsAg promoted epithelial-mesenchymal transition by upregulating vimentin and fibronectin in EBV-positive NPC cells in vitro, thereby promoting invasion and migration of EBV-positive NPC cells.Conclusions and RelevanceIn this cohort study, the observed synergistic association between HBsAg and plasma EBV DNA load represented a novel potential mechanism underlying the increased risk of distant metastasis in patients with NPC. Hence, attention should be paid to patients with NPC with HBsAg positivity, especially when the plasma EBV DNA level is 6 × 1000 copies/mL or greater. Consideration of this synergistic association will contribute to more accurate individualized management.

In this work, a floating electrode is employed to generate a stable large-area diffuse discharge plasma under an open oxygen-rich environment. The discharge image and the optical emission spectra of the N2(C-B), N 2 + (B-X), N2(B-A), and O(3p–3s, 777 nm) are measured to analyze the morphological and optical characteristics of the discharge. The effects of applied voltage, gas flow rate, and electrode gap on the reactive species, vibrational temperature and rotational temperature are investigated, and the discharge mode is discussed by simulating the electrostatic field before the breakdown. It is found that the changes of applied voltage and electrode gap causes the transition of the discharge modes among corona mode, diffuse discharge mode and spark mode. It is shown that the floating electrode can inhibit the transition from discharge to spark mode to a certain extent, which is conducive to maintaining the stability of discharge. As is vividly illustrated in this study, the increase of applied voltage or the decrease of electrode gap contributes to the generation of more active particles, such as N2(C) and N 2 + (B). Furthermore, the Joule heating effect becomes more evident with the increased applied voltage when the electrode gap is 15 and 20 mm. Moreover, as the applied voltage increases, the vibrational temperature increases at the electrode gap of 25 mm.

This work investigates a novel pulsating DC high-voltage linear driving scheme for GaN-based Light-emitting diode (GaN LED) general lighting to save costs and alleviate flicker. The superiority and practicality of this scheme in three-phase AC power grids were demonstrated for the first time. Compared to applications for single-phase AC grids, linear driving of GaN LEDs for three-phase AC grids can provide superior performance for general lighting. The DC component of the three-phase AC rectified voltage reaches 90.7%, which effectively alleviates the flicker problem. In this paper, we balanced GaN LED power and driving efficiency by optimizing the GaN LED distribution of the linear multi-string GaN LED driving scheme while taking the effects of grid voltage fluctuations into account. In addition, we constructed a double-string GaN LED lighting system as a modular prototype with scalability. The experimental results exhibit high driving efficiency (~94% @380 V line voltage), high power factor (~0.952), flicker-free, and high reliability at a very low cost (~$0.005/W).

HighlightsAlkaline hydrolysis is an effective way of managing livestock carcasses.The hydrolysates can be aerobically treated to prepare a nutrient solution.Mixing the nutrient solution with a traditional fertilizer increases lettuce quality.The fertilizer expenses of hydroponic lettuce growth can be reduced by 50%.Abstract. Animal mortality management is an essential part of livestock production. Choosing a proper method to handle mortalities is essential for preventing the spread of animal diseases and maintaining the sustainability of livestock facilities. The objectives of this study were (1) to test the efficacy of alkaline hydrolysis at ambient conditions to dispose of piglet mortalities, and (2) to demonstrate if the hydrolysates of the alkaline hydrolysis process could be used to grow lettuce hydroponically. Three alkaline concentrations (1M, 2M, and 4M) were tested to hydrolyze piglet mortalities. The pH of all alkaline solutions stayed above 12.8 for 31 days, which could eliminate all the pathogens that might concern swine producers based on previous studies. The hydrolysates were neutralized using corn silage with a pH of 3.9 ±0.2 and aerobically treated for 15 days. After aerobic treatment, mixing 20× diluted hydrolysates with 2× diluted control (commercially available fertilizer) provided the highest yields (on average, 18.2% more fresh weight compared to control). This mixture also yielded the highest chlorophyll and total soluble sugar content. We concluded that alkaline treatment of piglet mortalities at ambient temperature and pressure was feasible, and the neutralized and aerobically treated hydrolysates could be used to grow lettuce, reducing the risk of environmental releases. Keywords: Alkaline hydrolysis, Hydroponic, Hydrolysate, Livestock, Mortality, Real-time sensors.

To analyze the influence of the distance between tunnels at the bridge-tunnel junction in the mountainous area on the driving safety under crosswind, a vehicle dynamics model is established by Carsim software. Under the conditions of different driving speeds (60km/h, 80km/h and 100km/h), different wind scales (level 6-9) and three alignment combinations of the tunnels (tunnel-straight road-tunnel, tunnel-curving road-tunnel, tunnel-the combination of straight and curves road-tunnel), the vehicle's lateral offset and lateral force coefficient are used as evaluation indexes to study the influence of distance between tunnels on driving safety. When the distance is small, the lateral offset and lateral force coefficient of vehicle driving on the bridge-tunnel junction increase firstly and then decrease as the distance increases. But the changes of the lateral offset and lateral force coefficient are not synchronized, and the peak value of the lateral force coefficient occurs earlier than the lateral offset. Finally, the minimum safety spacing of each condition and speed limits for different distances are proposed. Under the condition of the straight-tunnel, 20m distance between tunnels cannot ensure the driving safety when the wind scale reaches level 9, and the road should be closed. Under the conditions of the curve and the combination of straights and curves, driving safety cannot be maintained at each spacing at wind scale level 8 and 9, and the road should be closed. However, when the wind speed is level 6 or 7, speed limits can be adopted to ensure driving safety. The results suggest that vehicles' lateral offset and lateral force coefficient can be effectively reduced by reducing the driving speed or increasing the distance between tunnels, so the risk of accidents caused by the crosswind can be reduced.

The pth moment stability of stochastic Markov jump systems (SMJSs) with time-delays and polynomial growth was investigated in this paper. Both the involved time-delays and polynomial growth are mod...

Natural product celastrol is known to have various biological activities, yet its molecular targets that correspond to many activities remain unclear. Here, we used multiple mass-spectrometry-based approaches to identify catechol-O-methyltransferase (COMT) as a major binding target of celastrol and characterized their interaction comprehensively. Celastrol was found to inhibit the enzymatic activity of COMT and increased the dopamine level in neuroendocrine chromaffin cells significantly. Our study not only revealed a novel binding target of celastrol but also provided a new scaffold and cysteine hot spot for developing new generation COMT inhibitors in combating neurological disorders.

Ultraviolet photodissociation (UVPD) experiments of protonated tryptamine ([Tryp+H]+) have been implemented by a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer combined with a ...

Purpose The aim of this study was to prepare and evaluate betulinic acid nanosuspension (BA-NS) for new drug delivery to enhance its solubility and in vitro anti-tumor activity. Methods BA-NS was formulated by an anti-solvent precipitation method using the Box-Behnken design (BBD). Particle size (PS) and Zeta potential were measured by laser particle size analysis. The drug solid state after freeze drying was characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and Fourier transform infrared spectroscopy (FTIR) after freeze drying. The saturation solubility and dissolution rate were determined by solubility assay and in vitro dissolution studies, respectively. The in vitro cytotoxicity assay was performed using 3-(4,5-dimethylthiazole)-2,5-diphenltetraazolium bromide (MTT) method. Results The PS was 129.7±12.2 nm having a Zeta potential of -28.1±4.5 mV and the polydispersity index (PDI) was 0.231±0.013, which confirmed that the nanosuspension was in the stable amorphous state. A series of characterization experiments demonstrated that nanoparticles retained original effective structure and existed as spherical or near-spherical nanoparticles in the nanosuspension, but the drug transferred from the crystal state to the amorphous state. The form of lyophilized BA-NS was very successful in enhancing the dissolution rate in PH-dependent way. The cytotoxicity assay revealed that BA-NS could significantly enhance the in vitro anti-proliferation against tumor cells compared to the BA suspension (BA-S). Conclusion The BA-NS can remarkably improve solubility and in vitro antitumor activity, which seems very promising for the treatment of cancers in practical application.

This study aimed to prepare icariside I (ICS I) and icariside II (ICS II) from

The low gain avalanche detectors (LGADs) are thin sensors with fast charge collection which in combination with internal gain deliver an outstanding time resolution of about 30 ps. High collision rates and consequent large particle rates crossing the detectors at the upgraded Large Hadron Collider (LHC) in 2028 will lead to radiation damage and deteriorated performance of the LGADs. The main consequence of radiation damage is loss of gain layer doping (acceptor removal) which requires an increase of bias voltage to compensate for the loss of charge collection efficiency and consequently time resolution. The Institute of High Energy Physics (IHEP), Chinese Academy of Sciences (CAS) has developed a process based on the Institute of Microelectronics (IME), CAS capability to enrich the gain layer with carbon to reduce the acceptor removal effect by radiation. After 1 MeV neutron equivalent fluence of 2.5$\times$10$^{15}$ n$_{eq}$/cm$^{2}$, which is the maximum fluence to which sensors will be exposed at ATLAS High Granularity Timing Detector (HGTD), the IHEP-IME second version (IHEP-IMEv2) 50 $μ$m LGAD sensors already deliver adequate charge collection > 4 fC and time resolution < 50 ps at voltages < 400 V. The operation voltages of these 50 $μ$m devices are well below those at which single event burnout may occur.

Objective Thyroid hormone autoantibody (THAb) is a common antibody in autoimmune disease and can interfere with the detection of thyroid hormone (TH). There was no research reporting the prevalence of THAb in Chinese and the rate of THAb interfering with TH detection. Methods We collected 114 patients with autoimmune thyroid disease (AITD) (Hashimoto's thyroiditis, 57 cases; Graves’ disease, 57 cases), 106 patients with nonthyroid autoimmune diseases (NTAID), and 120 healthy subjects. According to the presence or absence of thyroid antibodies, patients with NTAID were divided into two groups: NTAID‐AITD and NTAID groups. Radioimmunoprecipitation technique was used to detect THAb in all subjects. TH was detected on Abbot and Roche platforms in patients with positive THAb. Results The prevalence of THAb was 22.8% in Hashimoto's thyroiditis and 45.6% in Graves’ disease. The prevalence of THAb in AITD group was lower than that in NTAID or NTAID‐AITD groups (34.2% vs. 61.5%, p = 0.014; 34.2% vs. 71.3%, p, We firstly investigated THAb in Chinese patients, and we found the prevalence of THAb in AITD patients was lower than that in NTAID patients. Although THAb has a high frequency in various autoimmune diseases, the rate of THAb interfering with thyroid hormone detection was only 9.18%.

Mycobacterium tuberculosis (Mtb) infection is notoriously difficult to treat. Treatment efficacy is limited by Mtb’s intrinsic drug resistance, as well as its ability to evolve acquired resistance to all antituberculars in clinical use. A deeper understanding of the bacterial pathways that govern drug efficacy could facilitate the development of more effective therapies to overcome resistance, identify new mechanisms of acquired resistance, and reveal overlooked therapeutic opportunities. To define these pathways, we developed a CRISPR interference chemical-genetics platform to titrate the expression of Mtb genes and quantify bacterial fitness in the presence of different drugs. Mining this dataset, we discovered diverse and novel mechanisms of intrinsic drug resistance, unveiling hundreds of potential targets for synergistic drug combinations. Combining chemical-genetics with comparative genomics of Mtb clinical isolates, we further identified numerous new potential mechanisms of acquired drug resistance, one of which is associated with the emergence of a multidrug-resistant tuberculosis (TB) outbreak in South America. Lastly, we make the unexpected discovery of an “acquired drug sensitivity.” We found that the intrinsic resistance factor whiB7 was inactivated in an entire Mtb sublineage endemic to Southeast Asia, presenting an opportunity to potentially repurpose the macrolide antibiotic clarithromycin to treat TB. This chemical-genetic map provides a rich resource to understand drug efficacy in Mtb and guide future TB drug development and treatment.

Develop and evaluate a deep learning-based automatic meningioma segmentation method for preoperative meningioma differentiation using radiomic features.A retrospective multicentre inclusion of MR examinations (T1/T2-weighted and contrast-enhanced T1-weighted imaging) was conducted. Data from centre 1 were allocated to training (n = 307, age = 50.94 ± 11.51) and internal testing (n = 238, age = 50.70 ± 12.72) cohorts, and data from centre 2 external testing cohort (n = 64, age = 48.45 ± 13.59). A modified attention U-Net was trained for meningioma segmentation. Segmentation accuracy was evaluated by five quantitative metrics. The agreement between radiomic features from manual and automatic segmentations was assessed using intra class correlation coefficient (ICC). After univariate and minimum-redundancy-maximum-relevance feature selection, L1-regularized logistic regression models for differentiating between low-grade (I) and high-grade (II and III) meningiomas were separately constructed using manual and automatic segmentations; their performances were evaluated using ROC analysis.Dice of meningioma segmentation for the internal testing cohort were 0.94 ± 0.04 and 0.91 ± 0.05 for tumour volumes in contrast-enhanced T1-weighted and T2-weighted images, respectively; those for the external testing cohort were 0.90 ± 0.07 and 0.88 ± 0.07. Features extracted using manual and automatic segmentations agreed well, for both the internal (ICC = 0.94, interquartile range: 0.88-0.97) and external (ICC = 0.90, interquartile range: 0.78-70.96) testing cohorts. AUC of radiomic model with automatic segmentation was comparable with that of the model with manual segmentation for both the internal (0.95 vs. 0.93, p = 0.176) and external (0.88 vs. 0.91, p = 0.419) testing cohorts.The developed deep learning-based segmentation method enables automatic and accurate extraction of meningioma from multiparametric MR images and can help deploy radiomics for preoperative meningioma differentiation in clinical practice.• A deep learning-based method was developed for automatic segmentation of meningioma from multiparametric MR images. • The automatic segmentation method enabled accurate extraction of meningiomas and yielded radiomic features that were highly consistent with those that were obtained using manual segmentation. • High-grade meningiomas were preoperatively differentiated from low-grade meningiomas using a radiomic model constructed on features from automatic segmentation.

The development and application of cell-based biosensors (CBBs) provides a convenient strategy for rapid detection of target analytes. The CBBs had been widely applied in the fields of food safety, environment monitoring, and medicine diagnosis due to their advantages of short response time, easy operation, low toxicity, and portability. However, the CBBs based on two-dimensional (2D) cultured cells in-vitro suffer from a lower cell viability and isolated physiology, which had blocked the accurate evaluations of these biosensors. With the development of nanotechnology and three-dimensional (3D) printing technology, cells fixed in a 3D biosensor or a 3D microenvironment have shown great improvement in the sensitivity and detection authenticity than conventional CBBs. To promote the further development of CBBs, in this paper, we reviewed the related technologies used to construct 3D bionic cell chips including organic/inorganic agents and operating approaches suitable for constructing 3D cell cultural microenvironment. Then, the applications of 3D bionic cell chip based on microbial and mammalian cell biosensors in food safety field were discussed during recent ten years. Finally, the current challenges and further directions were summarized and prospected.

Acute myeloid leukemia (AML) is a complex hematologic malignancy. Survival rate of AML patients is low. N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) play important roles in AML tumorigenesis and progression. However, the relationship between lncRNAs and biological characteristics of AML, as well as how lncRNAs influence the prognosis of AML patients, remain unclear. In this study. In this study, Pearson correlation analysis was used to identify lncRNAs related to m6A regulatory genes, namely m6A-related lncRNAs. And we analyzed their roles and prognostic values in AML. m6A-related lncRNAs associated with patient prognosis were screened using univariate Cox regression analysis, followed by systematic analysis of the relationship between these genes and AML clinicopathologic and biologic characteristics. Furthermore, we examined the characteristics of tumor immune microenvironment (TIME) using different IncRNA clustering models. Using LASSO regression, we identified the risk signals related to prognosis of AML patients. We then constructed and verified a risk model based on m6A-related lncRNAs for independent prediction of overall survival in AML patients. Our results indicate that risk scores, calculated based on risk-related signaling, were related to the clinicopathologic characteristics of AML and level of immune infiltration. Finally, we examined the expression level of TRAF3IP2-AS1 in patient samples through real-time polymerase chain reaction analysis and in GEO datasets, and we identified a interaction relationship between SRSF10 and TRAF3IP2-AS1 through in vitro assays. Our study shows that m6A-related lncRNAs, evaluated using the risk prediction model, can potentially be used to predict prognosis and design immunotherapy in AML patients.

Succinate dehydrogenase inhibitors (SDHIs) have become one of the fastest growing classes of new fungicides since entering the market, and have attracted increasing attention as a result of their unique structure, high activity and broad fungicidal spectrum. The mechanism of SDHIs is to inhibit the activity of succinate dehydrogenase, thereby affecting mitochondrial respiration and ultimately killing pathogenic fungi. At present, they have become popular varieties researched and developed by major pesticide companies in the world. In the review, we focused on the mechanism, the history, the representative varieties, structure–activity relationship and resistance of SDHIs. Finally, the potential directions for the development of SDHIs were discussed. It is hoped that this review can strengthen the individuals’ understanding of SDHIs and provide some inspiration for the development of new fungicides.

We report precise TCAD simulations of IHEP-IME-v1 Low Gain Avalanche Diode (LGAD) calibrated by secondary ion mass spectroscopy (SIMS). Our setup allows us to evaluate the leakage current, capacitance, and breakdown voltage of LGAD, which agree with measurements' results before irradiation. And we propose an improved LGAD Radiation Damage Model (LRDM) which combines local acceptor removal with global deep energy levels. The LRDM is applied to the IHEP-IME-v1 LGAD and able to predict the leakage current well at -30 $^{\circ}$C after an irradiation fluence of $ \Phi_{eq}=2.5 \times 10^{15} ~n_{eq}/cm^{2}$. The charge collection efficiency (CCE) is under development.

This paper presents a modeling method for high power dielectric resonator (DR) filter. An efficient and accurate model for DR filter is developed by preserving only the necessary information of the generalized scattering matrix (GSM) for each junction of the filter structure. Doing so, the sizes of the GSMs are dramatically reduced for the training and testing of the neural network (NN) models of each critical junction of the DR filter. The neural models are subsequently connected using a transmission line model for each mode in a cylindrical dielectric rod with conductor housing. Calculations of the propagation constant for each mode are given. The final model contains NN and transmission line models and is thus very fast. The method is described in details using a Ku-band high power DR filter. Efficiency and accuracy of the model are demonstrated through comparison with full-wave simulations and measurements. Excellent agreements are observed for both near-band and wide-band results.

Single-stranded DNA (ssDNA) is widely generated during DNA metabolisms including DNA replication, repair and recombination and is susceptible to digestion by nucleases and secondary structure formation. It is vital for DNA metabolism and genome stability that ssDNA is protected and stabilized, which are performed by the major ssDNA-binding protein, and replication protein A (RPA) in these processes. In addition, RPA-coated ssDNA also serves as a protein-protein-binding platform for coordinating multiple events during DNA metabolisms. However, little is known about whether and how the formation of RPA-ssDNA platform is regulated. Here we highlight our recent study of a novel RPA-binding protein, Regulator of Ty1 transposition 105 (Rtt105) in Saccharomyces cerevisiae, which regulates the RPA-ssDNA platform assembly at replication forks. We propose that Rtt105 functions as an "RPA chaperone" during DNA replication, likely also promoting the assembly of RPA-ssDNA platform in other processes in which RPA plays a critical role.

Patients with nasopharyngeal carcinoma (NPC) who have hepatitis B virus (HBV) infection tend to be treated with induction chemotherapy (IC) due to a higher metastasis rate. However, additional IC may lead to immunosuppression and can negatively affect the prognosis. We evaluated whether receiving IC improved the prognosis of patients with NPC co-infected with HBV, on the basis of concurrent chemoradiotherapy (CCRT).This large-scale retrospective cohort study included data of patients with pathologically confirmed NPC that were collected from two hospitals between January 2010 and March 2014. Patients were followed-up every 3 months during the first 2 years and once every 6 months thereafter. Univariate analysis identified confounding factors associated with prognosis. Stage-based subgroup analyses and 1:1 random-matched pair analyses were performed to compare the survival differences between patients treated with IC + CCRT and those treated with CCRT alone.Among the 1,076 enrolled patients, 16.6% were hepatitis B surface antigen (HBsAg)-positive. Among HBsAg-positive patients with stage II/III/IV NPC, distant metastasis-free survival (DMFS) (79.3%Compared with CCRT alone, IC + CCRT negatively affects DMFS and PFS in patients with NPC with chronic HBV infection. We advocate withholding IC but administering stronger initial treatment in NPC patients complicated with HBV infection.

Nanocarbon materials are emerging as alternative activators of peroxymonosulfate (PMS) for organics decomposition. However, the relatively low activity and complex syntheses hindered their practical application and innovation with respect to rational design of carbocatalysts is highly desired. Herein, an in situ replication and transformation strategy was employed to facilely convert porous Fe3O4 microspheres into novel Fe/N codoped large-pore mesoporous carbon spheres (M‑Fe/NC) as Fenton-like catalysts for PMS activation. Benefiting from the abundance of active sites induced by dual heteroatom doping, the enhanced active site exposure due to the unique mesoporous structure, and the high stability of carbon component, the derived M‑Fe/NC was superior to the pristine Fe3O4 for PMS activation to degrade various organics and was efficient over a wide pH range (2-9). Compared with the proposed mechanisms of previous reports, both radical (surface-bound SO4- and OH) and nonradical (1O2 and direct oxidation) pathways are involved in the M‑Fe/NC/PMS system. Furthermore, experimental observations in combination with DFT calculations reveal that graphitic N and FeN4 sites serve as dual reaction centers in the catalysis. This research opened an avenue for development of novel multi-doped carbocatalysts used to activate PMS for sustainable remediation.

Herein, an ultramild block polymerization strategy was employed to precisely control the exposure of structural terminations in the skeleton of covalent triazine-based frameworks (CTFs). The generated structural terminations with cyano (–CN) and hydroxy (–OH) groups (STCHs) could serve as not only the optimal adsorption sites for enriching targets, but also π-conjugated electron donor–acceptor dyads to accelerate the charge transfer. With spatial separation of charge localization sites, STCH-CTF exhibited a photoactivity of 2.5–4 times higher than that of pristine CTFs in the simultaneous oxidation of bisphenol A (BPA) and the reduction of hexavalent chromium (Cr(VI)).

Purpose: Immunoassay is susceptible to interference by other substances in the serum. The main substances interfering with thyroid function testing include heterophilic antibody, biotin, thyroid hormone autoantibody, and Macro-TSH. We reported a patient with fraudulently elevated FT4 and TSH and described various common experimental methods used to explore the existence of substances interfering with thyroid function testing.Methods and Results: FT4 and TSH were significantly lower when measured on the Architect platform (FT4: 7.09 pmol/L, TSH: 58.94 µIU/ml). Polyethylene glycol precipitation showed lower FT4 and TSH, suggesting the presence of a high molecular weight interfering substance. Heterophile blocking tube study showed heterophilic antibody interfered with TSH detection. 125I-hTSH binding study and radioimmunoprecipitation assay indicated that the patient didn’t contain anti-TSH autoantibody. The new generation of Elecsys immunoassay kit indicated that biotin interfered with TSH detection. Radioimmunoprecipitation assay showed that all four kinds of thyroid hormone autoantibodies were positive. After reviewing 24 literatures, we provided the diagnostic strategy for investigation of interferences with thyroid function immunoassays.Conclusion: We reported a case with falsely elevated TSH due to the combined action of heterophilic antibody and biotin and fraudulently elevated FT4 caused by thyroid hormone autoantibody. When there is a discrepancy between thyroid function and clinical manifestation, the presence of immunoassay interference with one or more indicators needs to be considered.

Introduction: Thyroid-stimulating hormone receptor (TSHR) is widely expressed in human tissues and cells. TSHR is not only involved in thyroid disease but also in the neuroendocrine-immune regulatory network. However, no study has exclusively focused on the expression and function of TSHR in natural killer (NK) cells. Methods: We studied TSHR expression using reverse transcription PCR to verify TSHR mRNA transcripts in human and mouse NK cells. Human and mouse thyroid and liver tissues as well as peripheral blood mononuclear cells (PBMCs) or spleen lymphoid cells (SLCs) were used as controls. The TSHR protein levels in NK-92 cells were determined by immunofluorescence staining. The function of TSHR in NK cells was investigated by measuring the TSH-stimulated cAMP levels. Results: TSHR mRNA was detected in human and mouse NK cells as well as in NK-92 cells and had the same sequence as that of thyroid-derived, PBMC-derived, and liver-derived mRNA. The TSHR protein was also expressed in the cell membrane of NK-92 cells. Furthermore, the cAMP levels in NK-92 cells were significantly higher after adding 102 mIU/mL of bovine TSH at p < 0.05, which stimulated cAMP production in NK-92 cells. Conclusions: Our findings confirm that TSHR is present and functional in NK cells and provide key clues for the potential regulatory effects of TSH on TSHR in NK cells in the immune system.