EBV abortive lytic cycle promotes nasopharyngeal carcinoma progression through recruiting monocytes and regulating their directed differentiation.

Epstein-Barr virus (EBV) is associated with several types of human cancer including nasopharyngeal carcinoma (NPC). The activation of EBV to the lytic cycle has been observed in advanced NPC and is believed to contribute to late-stage NPC development. However, how EBV lytic cycle promotes NPC progression remains elusive. Analysis of clinical NPC samples indicated that EBV reactivation and immunosuppression were found in advanced NPC samples, as well as abnormal angiogenesis and invasiveness. To investigate the role of the EBV lytic cycle in tumor development, we established a system that consists of two NPC cell lines, respectively, in EBV abortive lytic cycle and latency. In a comparative analysis using this system, we found that the NPC cell line in EBV abortive lytic cycle exhibited the superior chemotactic capacity to recruit monocytes and polarized their differentiation toward tumor-associated macrophage (TAM)-like phenotype and away from DCs, compared to EBV-negative or EBV-latency NPC cells. EBV-encoded transcription activator ZTA is responsible for regulating monocyte chemotaxis and TAM phenotype by up-regulating the expression of GM-CSF, IL-8, and GRO-α. As a result, TAM induced by EBV abortive lytic cycle promotes NPC angiogenesis, invasion, and migration. Overall, this study elucidated the role of the EBV lytic life cycle in the late development of NPC and revealed a mechanism underlying the ZTA-mediated establishment of the tumor microenvironment (TME) that promotes NPC late-stage progression.

A new lysosome-targeted fluorescent probe for hydrogen peroxide based on a benzothiazole derivative.

As an important member of reactive oxygen species, hydrogen peroxide (H2O2) plays a key role in oxidative stress and cell signaling. Abnormal levels of H2O2 in lysosomes can induce damage or even loss of lysosomal function, leading to certain diseases. Therefore, real-time monitoring of H2O2 in lysosomes is very important. In this work, we designed and synthesized a novel lysosome-targeted fluorescent probe for H2O2-specific detection based on a benzothiazole derivative. A morpholine group was used as a lysosome-targeted unit and a boric acid ester was chosen as the reaction site. In the absence of H2O2, the probe exhibited very weak fluorescence. In the presence of H2O2, the probe showed an increased fluorescence emission. The fluorescence intensity of the probe for H2O2 displayed a good linear relationship in the concentration range of H2O2 from 8.0 × 10-7 to 2.0 × 10-4 mol·L-1. The detection limit was estimated to be 4.6 × 10-7 mol·L-1 for H2O2. The probe possessed high selectivity, good sensitivity and short response time for the detection of H2O2. Moreover, the probe had almost no cytotoxicity and had been successfully applied to confocal imaging of H2O2 in lysosomes of A549 cells. These results illustrated that the developed fluorescent probe in this study could provide a good tool for the determination of H2O2 in lysosomes.

Effect of enzymatic hydrolysis of arabinoxylan on the quality of frozen dough during the subfreezing process.

BACKGROUND: The objective of this investigation was to examine the impact of enzymatic hydrolysis of arabinoxylan (AX) on frozen dough quality under subfreezing conditions. The dough was subjected to freezing at -40 °C for 2 h and then stored at -9, -12, and -18 °C for 15 days. The water loss, freezable water content, water migration, and microstructure of the dough were measured. RESULTS: The dough containing 0.8% cellulase enzymatically hydrolyzed AX (CAX) required the shortest duration when traversing the maximum ice-crystal formation zone (6.5 min). The dough with xylanase enzymatically hydrolyzed AX (XAX) demonstrated a faster freezing rate than the dough with CAX. The inclusion of both XAX and CAX in the dough resulted in the lowest freezable water loss and reduced freezable water content and free-water content levels, whereas the inclusion of xylanase-cellulase combined with enzymatically hydrolyzed AX resulted in higher free-water content levels. The textural properties of the subfreezing temperature dough were not significantly different from the dough stored at -18 °C and sometimes even approached or surpassed the quality observed in the control group rather than the dough stored at -18 °C. In addition, the gluten network structure remains well preserved in XAX- and CAX-containing doughs with minimal starch damage. CONCLUSION: The enzymatic hydrolysis of AX from wheat bran can be used as a useful additive to improve the quality of frozen dough. © 2024 Society of Chemical Industry.

Integration of MnO2 Nanosheets with Pd Nanoparticles for Efficient CO2 Electroreduction to Methanol in Membrane Electrode Assembly Electrolyzers.

It remains a challenge to design a catalyst with high selectivity at a large current density toward CO2 electrocatalytic reduction (CO2ER) to a single C1 liquid product of methanol. Here, we report the design of a catalyst by integrating MnO2 nanosheets with Pd nanoparticles to address this challenge, which can be implemented in membrane electrode assembly (MEA) electrolyzers for the conversion of CO2ER to methanol. Such a strategy modifies the electronic structure of the catalyst and provides additional active sites, favoring the formation of key reaction intermediates and their successive evolution into methanol. The optimal catalyst delivers a Faradaic efficiency of 77.6 ± 1.3% and a partial current density of 250.8 ± 4.3 mA cm-2 for methanol during CO2ER in an MEA electrolyzer by coupling anodic oxygen evolution reaction with a full-cell energy efficiency achieving 29.1 ± 1.2% at 3.2 V. This work opens a new avenue to the control of C1 intermediates for CO2ER to methanol with high selectivity and activity in an MEA electrolyzer.

Epstein-Barr Virus LMP1-Activated mTORC1 and mTORC2 Coordinately Promote Nasopharyngeal Cancer Stem Cell Properties.

Epstein-Barr virus (EBV) is associated with several malignant diseases, including Burkitt's lymphoma, nasopharyngeal carcinoma (NPC), certain types of lymphomas, and a portion of gastric cancers. The virus-encoded oncoprotein, LMP1, induces the epithelial-to-mesenchymal transition (EMT), leading to cancer stem cell formation. In the current study, we investigated how LMP1 contributes to cancer stem cell development in NPC. We found that LMP1 plays an essential role in acquiring cancer stem cell (CSC) characteristics, including tumor initiation, metastasis, and therapeutic resistance by activating the PI3K/mTOR/Akt signaling pathway. We dissected the functions of distinct signaling (mTORC1 and mTORC2) in the acquisition of different CSC characteristics. Side population (SP) formation, which represents the chemotherapy resistance feature of CSC, requires mTORC1 signaling. Tumor initiation capability is mainly attributed to mTORC2, which confers on NPC the capabilities of proliferation and survival by activating mTORC2 downstream genes c-Myc. Both mTORC1 and mTORC2 enhance cell migration and invasion of NPC cells, suggesting that mTORC1/2 coregulate metastasis of NPC. The revelation of the roles of the mTOR signaling pathways in distinct tumorigenic features provides a guideline for designing efficient therapies by choosing specific mTOR inhibitors targeting mTORC1, mTORC2, or both to achieve durable remission of NPC in patients. IMPORTANCE LMP1 endows NPC to gain cancer stem cell characteristics through activating mTORC1 and mTORC2 pathways. The different mTOR pathways are responsible for distinct tumorigenic features. Rapamycin-insensitive mTORC1 is essential for CSC drug resistance. NPC tumor initiation capacity is mainly attributed to mTORC2 signaling. mTORC1 and mTORC2 coregulate NPC cell migration and invasion. The revelation of the roles of mTOR signaling in NPC CSC establishment has implications for novel therapeutic strategies to treat relapsed and metastatic NPC and achieve durable remission.

EBV latent membrane proteins promote hybrid epithelial-mesenchymal and extreme mesenchymal states of nasopharyngeal carcinoma cells for tumorigenicity.

EBV-encoded LMPs are consistently detected in nasopharyngeal carcinoma (NPC). Recent evidence suggests potential roles of LMP1 and LMP2A in Epithelial-to-mesenchymal transition (EMT) process in NPC. EMT engages in the generation and maintenance of cancer stem cells (CSCs) and confers on cancer cells increased tumor-initiating and metastatic potential, and higher resistance to anticancer therapies. However, how LMP1 and LMP2A regulate the EMT process to generate cells with different EMT states and its implications for tumor progression remain unclear. Here we report that LMP1 and LMP2A promote EMT that drives NPC cells from the epithelial-like state (E) (CD104+, CD44low) to epithelial-mesenchymal hybrid (E/M) state (CD104+, CD44high). Furthermore, LMP2A possesses an additional function in stabilizing LMP1 and increasing the level of LMP1 in NPC cells. The elevated LMP1 further forces the EMT to generate extreme-mesenchymal (xM) state cells (CD104-, CD44high). To define the tumorigenic features of cancer stem cells at different states in the EMT spectrum, E, E/M and xM subpopulations were isolated and tested for tumorigenic capability in a tumor xenograft animal model. We found that the cells with E/M phenotypes possess the highest tumor initiating capacity. However, the xM subpopulation exhibits increased vasculogenic mimicry, a hallmark of metastatic cancers. Taken together, coordinated action of LMP1 and LMP2A generates an array of intermediate subpopulations in the EMT spectrum that are responsible for distinct tumorigenic features of NPC such as tumor-initiation, vasculogenesis, and metastasis.

Deep learning-based lesion detection and severity grading of small-bowel Crohn's disease ulcers on double-balloon endoscopy images.

BACKGROUND AND AIMS: Double-balloon endoscopy (DBE) is widely used in diagnosing small-bowel Crohn's disease (CD). However, CD misdiagnosis frequently occurs if inexperienced endoscopists cannot accurately detect the lesions. The CD evaluation may also be inaccurate owing to the subjectivity of endoscopists. This study aimed to use artificial intelligence (AI) to accurately detect and objectively assess small-bowel CD for more refined disease management. METHODS: We collected 28,155 small-bowel DBE images from 628 patients from January 2018 to December 2022. Four expert gastroenterologists labeled the images, and at least 2 endoscopists made the final decision with agreement. A state-of-the-art deep learning model, EfficientNet-b5, was trained to detect CD lesions and evaluate CD ulcers. The detection included lesions of ulcer, noninflammatory stenosis, and inflammatory stenosis. Ulcer grading included ulcerated surface, ulcer size, and ulcer depth. A comparison of AI model performance with endoscopists was performed. RESULTS: The EfficientNet-b5 achieved high accuracies of 96.3% (95% confidence interval [CI], 95.7%-96.7%), 95.7% (95% CI, 95.1%-96.2%), and 96.7% (95% CI, 96.2%-97.2%) for the detection of ulcers, noninflammatory stenosis, and inflammatory stenosis, respectively. In ulcer grading, the EfficientNet-b5 exhibited average accuracies of 87.3% (95% CI, 84.6%-89.6%) for grading the ulcerated surface, 87.8% (95% CI, 85.0%-90.2%) for grading the size of ulcers, and 85.2% (95% CI, 83.2%-87.0%) for ulcer depth assessment. CONCLUSIONS: The EfficientNet-b5 achieved high accuracy in detecting CD lesions and grading CD ulcers. The AI model can provide expert-level accuracy and objective evaluation of small-bowel CD to optimize the clinical treatment plans.

Over 70 % Faradaic Efficiency for CO2 Electroreduction to Ethanol Enabled by Potassium Dopant-Tuned Interaction between Copper Sites and Intermediates.

It is highly desired yet challenging to steer the CO2 electroreduction reaction (CO2 ER) toward ethanol with high selectivity, for which the evolution of reaction intermediates on catalytically active sites holds the key. Herein, we report that K doping in Cu2 Se nanosheets array on Cu foam serves as a versatile way to tune the interaction between Cu sites and reaction intermediates in CO2 ER, enabling highly selective production of ethanol. As revealed by characterization and simulation, the electron transfer from K to Se can stabilize CuI species which facilitate the adsorption of linear *COL and bridge *COB intermediates to promote C-C coupling during CO2 ER. As a result, the optimized K11.2% -Cu2 Se nanosheets array can catalyze CO2 ER to ethanol as a single liquid product with high selectivity in a potential area from -0.6 to -1.2 V. Notably, it offers a Faradaic efficiency of 70.3 % for ethanol production at -0.8 V with as is stable for 130 h.

The mTOR inhibitor manassantin B reveals a crucial role of mTORC2 signaling in Epstein-Barr virus reactivation.

Lytic replication of Epstein-Barr virus (EBV) is not only essential for its cell-to-cell spread and host-to-host transmission, but it also contributes to EBV-induced oncogenesis. Thus, blocking EBV lytic replication could be a strategy for managing EBV-associated diseases. Previously, we identified a series of natural lignans isolated from the roots of Saururus chinensis (Asian lizard's tail) that efficiently block EBV lytic replication and virion production with low cytotoxicity. In this study, we attempted to elucidate the molecular mechanism by which these lignans inhibit EBV lytic replication. We found that a representative compound, CSC27 (manassantin B), inhibits EBV lytic replication by suppressing the expression of EBV immediate-early gene BZLF1 via disruption of AP-1 signal transduction. Further analysis revealed that manassantin B specifically blocks the mammalian target of rapamycin complex 2 (mTORC2)-mediated phosphorylation of AKT Ser/Thr protein kinase at Ser-473 and protein kinase Cα (PKCα) at Ser-657. Using phosphoinositide 3-kinase-AKT-specific inhibitors for kinase mapping and shRNA-mediated gene silencing, we validated that manassantin B abrogates EBV lytic replication by inhibiting mTORC2 activity and thereby blocking the mTORC2-PKC/AKT-signaling pathway. These results suggest that mTORC2 may have utility as an antiviral drug target against EBV infections and also reveal that manassantin B has potential therapeutic value for managing cancers that depend on mTORC2 signaling for survival.

Efficacious CO2 Adsorption and Activation on Ag Nanoparticles/CuO Mesoporous Nanosheets Heterostructure for CO2 Electroreduction to CO.

It is an ongoing pursuit for researchers to precisely control the catalyst's surface for high-performance CO2 electrochemical reduction (CO2ER). In this work, CuO mesoporous nanosheets (CuO MNSs) with rough edges decorated by small Ag nanoparticles (Ag NPs) with a tunable amount of Ag were synthesized on a Cu foil at normal atmospheric temperature through two-step solution-phase reactions for CO2ER to CO. In this special Ag NPs/CuO MNSs heterostructure, the mesoporous CuO NSs with rough edges favored gas infiltration, while decorated Ag NPs expanded the active sites for CO2 molecule adsorption. Ag NPs endowed Ag NPs/CuO MNSs with good electrical conductivity and promoted the adsorbed CO2 molecules to obtain electrons from the catalyst. Especially, the Ag-CuO interface stabilized the *COOH intermediate with strong bonding, which is important in boosting CO2ER to CO. The optimal Ag1.01%/CuO can catalyze CO2ER to CO with a Faradaic efficiency of 91.2% and a partial current density of 10.5 mA cm-2 at -0.7 V. Moreover, it exhibited prominent catalytic stability, retaining 97.8% of the initial current density and 97.6% of the original Faradaic efficiency for CO after 12 h of testing at -0.7 V. Notably, the Faradaic efficiency of CO on Ag1.01%/CuO can retain over 80% in the potential area from -0.6 to -0.9 V, embodying its high selectivity for CO. This work develops precious metal/metal oxide heterostructures with a low precious metal loading for efficacious CO2ER to CO and beyond.

A multi-conformational virtual screening approach based on machine learning targeting PI3Kγ.

Nowadays, more and more attention has been attracted to develop selective PI3Kγ inhibitors, but the unique structural features of PI3Kγ protein make it a very big challenge. In the present study, a virtual screening strategy based on machine learning with multiple PI3Kγ protein structures was developed to screen novel PI3Kγ inhibitors. First, six mainstream docking programs were chosen to evaluate their scoring power and screening power; CDOCKER and Glide show satisfactory reliability and accuracy against the PI3Kγ system. Next, virtual screening integrating multiple PI3Kγ protein structures was demonstrated to significantly improve the screening enrichment rate comparing to that with an individual protein structure. Last, a multi-conformational Naïve Bayesian Classification model with the optimal docking programs was constructed, and it performed a true capability in the screening of PI3Kγ inhibitors. Taken together, the current study could provide some guidance for the docking-based virtual screening to discover novel PI3Kγ inhibitors.

Mono-ubiquitylated ORF45 Mediates Association of KSHV Particles with Internal Lipid Rafts for Viral Assembly and Egress.

Herpesviruses acquire their envelope by budding into the lumen of cytoplasmic membrane vesicles. This process is initiated by component(s) on viral particles, which recognize the budding site where the viral glycoproteins are present and recruit cellular cargo transport and sorting machinery to the site to complete the budding process. Proteins in the tegument layer, connecting capsid and envelope, are candidates for the recognition of budding sites on vesicle membrane and induction of budding and final envelopment. We examined several outer and matrix tegument proteins of Kaposi's sarcoma-associated herpesvirus (KSHV) and found that ORF45 associates with lipid rafts (LRs) of cellular membrane. LRs are membrane micro-domains, which have been implicated as relay stations in intracellular signaling and transport including viral entry and virion assembly. The ability of ORF45 to target LR is dependent on the mono-ubiquitylation of ORF45 at Lys297 as the mutation at Lys297 (K297R) abolished LR-association of ORF45. The K297R mutation also impairs ORF45 and viral particle co-localization with trans-Golgi network and endosomes, but facilitates ORF45 and viral particles co-localizing with lysosomes. More importantly, the recombinant KSHV carrying ORF45 K297R mutant (BAC-K297R) was found severely defective in producing mature and infectious virion particles in comparison to wild type KSHV (BAC16). Taken together, our results reveal a new function of KSHV tegument protein ORF45 in targeting LR of host cell membrane, promoting viral particles co-localization with trans-Golgi and endosome vesicles and facilitating the maturation and release of virion particles, suggesting that ORF45 plays a role in bringing KSHV particles to the budding site on cytoplasmic vesicle membrane and triggering the viral budding process for final envelopment and virion maturation.

Type 2 diabetes, insulin treatment and prognosis of breast cancer.

BACKGROUND: The aim of our study was to investigate whether pre-existing type 2 diabetes and insulin therapy have an impact on the prognosis of breast cancer patients. METHODS: We performed a retrospective analysis of 462 type 2 diabetic breast cancer patients and 1644 non-diabetic breast cancer patients treated in our institute from January 2005 to August 2010. Patients were divided by diabetes status and insulin use. The clinicopathological characteristics and clinical outcomes of patients within 5 years following breast cancer diagnosed were analysed. RESULTS: Diabetic patients tended to have higher body mass index and higher histological grade tumours. Five-year disease-free survival and overall survival were reduced in diabetic patients (P < 0.001), and diabetes was an independent predictor for an increased risk of breast cancer relapse and death within 5 years (P < 0.001). Insulin treatment was associated with reduced 5-year disease-free survival and overall survival (P < 0.05); the risk of 5-year relapse and breast cancer mortality in the insulin group increased compared to that of non-insulin group after adjusting for age, tumour size, histological grade, oestrogen receptor, progesterone receptor, chemotherapy and hormone therapy (P < 0.05). After adjusting for age and other factors, the risk of breast cancer relapse was also increased in the insulin subgroup, while the risk of breast cancer mortality did not increase statistically. CONCLUSIONS: Type 2 diabetes and insulin treatment might be independently associated with poorer prognosis of breast cancer. However, caution is needed when interpreting our results, and further investigations are needed. Copyright © 2016 John Wiley & Sons, Ltd.

Surface roughness prediction model and experimental results based on multi-wavelength fiber optic sensors.

The surface roughness prediction model based on a support vector machine was proposed and the multi-wavelength fiber optic sensor was established. The specimens with different surface roughness selected as the test samples were analyzed by using the prediction model when the incident wavelengths were 650 nm and 1310 nm, respectively. The working distance of 2.5 mm ~3.5 mm was chosen as the optimum measurement distance. The experimental results indicate that the error range of surface roughness is 0.74% ~7.56% at 650 nm, and the error range of surface roughness is 1.03% ~5.92% at 1310 nm. The average relative error is about 2.669% at 650 nm, while it is about 2.431% at 1310 nm. The error of roughness measurement is less than 3% by using the model, which is acceptable. The error of surface roughness based on the prediction model is smaller than that by using the characteristic curves between surface roughness and the scattering intensity ratio.

Drosophila Smt3 negatively regulates JNK signaling through sequestering Hipk in the nucleus.

Post-translational modification by the small ubiquitin-related modifier (SUMO) is important for a variety of cellular and developmental processes. However, the precise mechanism(s) that connects sumoylation to specific developmental signaling pathways remains relatively less clear. Here, we show that Smt3 knockdown in Drosophila wing discs causes phenotypes resembling JNK gain of function, including ectopic apoptosis and apoptosis-induced compensatory growth. Smt3 depletion leads to an increased expression of JNK target genes Mmp1 and puckered. We show that, although knockdown of the homeodomain-interacting protein kinase (Hipk) suppresses Smt3 depletion-induced activation of JNK, Hipk overexpression synergistically enhances this type of JNK activation. We further demonstrate that Hipk is sumolylated in vivo, and its nuclear localization is dependent on the sumoylation pathway. Our results thus establish a mechanistic connection between the sumoylation pathway and the JNK pathway through the action of Hipk. We propose that the sumoylation-controlled balance between cytoplasmic and nuclear Hipk plays a crucial role in regulating JNK signaling.

The role of cytolethal distending toxin in Glaesserella parasuis JS0135 strain infection: Cytotoxicity, phagocytic resistance and pathogenicity.

Glaesserella parasuis is an important porcine pathogen that commonly colonizes the upper respiratory tract of pigs and is prone to causing Glässer's disease under complex conditions. As yet, the disease has led to serious economic losses to the swine industry worldwide. Studies so far have found that several virulence factors are associated with the pathogenicity of G. parasuis, but the pathogenic mechanism is still not fully understood. Cytolethal distending toxin (CDT), a potential virulence factor in G. parasuis, is involved in cytotoxicity, serum resistance, adherence to and invasion of host cells in vitro. Here, to further investigate the pathogenic role of CDT during G. parasuis infection in vitro and in vivo, a double cdt1 and cdt2 deletion mutant (Δcdt1Δcdt2) without selectable marker was first generated in G. parasuis JS0135 strain by continuous natural transformations and replica plating. Morphological observation and lactate dehydrogenase assay showed that the Δcdt1Δcdt2 mutant was defective in cytotoxicity. Additionally, the Δcdt1Δcdt2 mutant was more susceptible to phagocytosis caused by 3D4/2 macrophages compared to the wild-type JS0135 strain. Moreover, by focusing on clinical signs, necropsy, bacterial recovery and pathological observation, we found that the deletion of cdt1 and cdt2 genes led to a significant attenuation of virulence in G. parasuis. Taken together, these findings suggest that as an important virulence factor, CDT can significantly affect the pathogenicity of G. parasuis.

Nonstoichiometry-Induced Self-Activated Phosphors for Dynamic Anti-counterfeiting Applications.

Optical signals with distinctive properties, such as contactless, fast response, and high identification, are harnessed to realize advanced anti-counterfeiting. However, the simultaneous attainment of multi-color, -temporal, and -modal luminescence performance remains a compelling and imperative pursuit. In our work, a temperature/photon-responded dynamic self-activated luminescence originating from nonstoichiometric Zn2GeO4 is developed with the modulation of intrinsic defects. The increased concentration of oxygen vacancies (VO••) contributes to an enhanced recombination of ZnGe″-VO••, ultimately improving the self-activated luminescence performance. Additionally, the photoluminescence (PL) color of the representative Zn2.2GeO4 sample changes from green to blue-white with the increased ultraviolet (UV) irradiation time. Concurrently, the emission color undergoes a variation from blue to green as the ambient temperature raises from 280 to 420 K. Remarkably, green long persistent luminescence (LPL) and photostimulated luminescence (PSL) behaviors are observed. Herein, this study elucidates a sophisticated anti-counterfeiting approach grounded in the dynamic luminescent attributes of nonstoichiometric Zn2GeO4, presenting a promising frontier for the evolution of anti-counterfeiting technologies.

Time-Frequency Characteristics and Evolution Law of Acoustic Emission Signals during the Deformation and Failure of Deformed Coal.

The research on the time-frequency characteristics and evolution law of acoustic emission (AE) signals during deformed coal failure is more conducive to understand the damage mechanism of coal. In this study, the experiments of AE monitoring during the intact and deformed coal failure were first conducted under loading axial stress and unloading confining stress conditions. Based on the evolution characteristics of volume strain and AE event rate, the damage process of coal was divided into three stages: nonfracture development stage, stable development stage of fracture, and unstable development stage of fracture. The distribution and evolution of AE waveform time-frequency properties under different damage processes were then analyzed and discussed. Besides, the evolution of the average value of different time-frequency parameters per 200 s for the intact coal and per 25 s for the deformed coal was discussed. The results show that the amplitude of most AE events stabilizes in 40-50 dB during the intact and deformed coal failure. The average amplitude of the deformed coal has an approximate positive correlation with the loading stress. The percentage of AE events with longer duration and rise time increases suddenly before the peak stress for the intact coal and after the peak stress for the deformed coal, which corresponds to the abrupt increase property of the average duration and rise time. For the frequency properties, the peak frequency and frequency centroid of the intact coal are distributed within 50-125 and 75-150 kHz, with those of the deformed coal located within 20-120 and 80-130 kHz, respectively. The average peak frequency and frequency centroid of the intact coal show an upward trend except for the initial fracture closure stage, while the average peak frequency and average frequency centroid of the deformed coal present a downward trend before the peak stress and have a smaller growth after the peak stress. According to the above-mentioned analysis, the sudden increase of the average duration and rise time, the lower average peak frequency, and the lower frequency centroid can be regarded as the precursor for the instability and failure of deformed coal. This research can provide a new idea and theoretical guidance for the early warning of outbursts.

Differential expression of zinc finger CCHC-type superfamily proteins in thyroid carcinoma and their associations with tumor immunity.

BACKGROUND: The zinc-finger CCHC-type (ZCCHC) superfamily proteins are characterized by the shared sequence CX2-CX4-HX4-C and thought to own high affinity to single-stranded nucleic acids, particularly RNAs. In humans, a total of 24 ZCCHC proteins have been annotated in the HUGO Gene Nomenclature Committee (HGNC, https://www.genenames.org/ ) database with most of these members involved in multiple steps of RNA metabolism. Many studies have indicated that the ZCCHC genes play a regulatory role in the development and progression of solid tumors. To date, the expression pattern and prognostic value of ZCCHC factors in thyroid carcinomas have not been reported. METHODS: Bioinformatics analyses on the functions of ZCCHC factors in thyroid carcinoma (THCA) patients were performed based on various databases, i.e., TCGA, GEPIA, Kaplan-Meier Plotter, and TIMER. RESULTS: Compared with normal tissues, the expression of ZCCHC12 mRNA was significantly increased in THCA tissues. And it was associated with the overall survival of THCA patients, based on the Kaplan-Meier Plotter database. Furthermore, the expression levels of all ZCCHCs were correlated with tumor stages, implying its high relevance to THCA, specifically its immunity. CONCLUSION: The ZCCHC genes, represented by ZCCHC12, are differentially expressed in THCA staging. These genes are associated with immune infiltration of THCA and identified as the potential therapeutic targets for immunotherapy in THCA patients, which are possible novel biomarkers for the treatment of THCA.

Bidirectional motivated bimodal isothermal strand displacement amplifier with a table tennis-like movement for the ultrasensitive fluorescent and colorimetric detection of depression-related microRNA.

An increasing number of studies have highlighted the potential of microRNAs (miRNAs) as physiological indicators of major depressive disorder (MDD). Herein, we developed a bidirectional-motivated bimodal isothermal strand displacement amplifier (BB-ISDA) for the ultrasensitive fluorescent and colorimetric detection of MDD-related miRNA-132. In the BB-ISDA system, a pair of functionalized hairpin probes (HP1 and HP2) with nicking recognition sites are designed to recognize target miRNA. The recognition of target miRNA by HP1 (or HP2) generates copious numbers of nicked triggers by HP1 (or HP2)-based ISDA to recognize HP2 (or HP1) by autonomous strand polymerization, cleavage, and displacement, which in turn induces the subsequent generation of copious numbers of nicked G-quadruplex triggers by HP2 (or HP1)-based ISDA to recognize HP1 (or HP2) along a same line. After many cycles, this bidirectional motivated table-tennis-like movement amplifies the fluorescent signal from HP1 and the colorimetric signal from HP2, simultaneously. The dual-signal output pattern was cross-validated for sensing miRNA-132. Each of the detection modal shows the capability for qualitative and quantitative detection of miRNA-132 with high sensitivity and specificity. The adaptability of the bimodal mechanism was verified via the detection of target miRNA-132 from clinical human blood samples. We envision that this BB-ISDA with dual-signal output for accurate and reliable analysis of miRNA is promising for the molecular diagnosis of human mental diseases.