Dynamical modelling of viral infection and cooperative immune protection in COVID-19 patients.

Once challenged by the SARS-CoV-2 virus, the human host immune system triggers a dynamic process against infection. We constructed a mathematical model to describe host innate and adaptive immune response to viral challenge. Based on the dynamic properties of viral load and immune response, we classified the resulting dynamics into four modes, reflecting increasing severity of COVID-19 disease. We found the numerical product of immune system's ability to clear the virus and to kill the infected cells, namely immune efficacy, to be predictive of disease severity. We also investigated vaccine-induced protection against SARS-CoV-2 infection. Results suggested that immune efficacy based on memory T cells and neutralizing antibody titers could be used to predict population vaccine protection rates. Finally, we analyzed infection dynamics of SARS-CoV-2 variants within the construct of our mathematical model. Overall, our results provide a systematic framework for understanding the dynamics of host response upon challenge by SARS-CoV-2 infection, and this framework can be used to predict vaccine protection and perform clinical diagnosis.

Molecular Classification of Endometrial Endometrioid Carcinoma With Microcystic Elongated and Fragmented Pattern.

The studies on the molecular classification of endometrioid carcinoma (EC) with microcystic, elongated, and fragmented (MELF) pattern invasion are limited. In this study, 77 cases of ECs with MELF patterns in Chinese women were collected. The molecular classification of the fifth edition of the World Health Organization was used to classify the molecular subtypes using immunohistochemistry staining (mismatch repair [MMR]-immunohistochemistry: MSH2, MSH6, MLH1, and PMS2; p53) and Sanger sequencing targeted POLE . The results showed that the prevalence of the 4 molecular subtypes in EC with MELF pattern was 6.5% (5/77) for POLE mutation, 20.8% (16/77) for MMR deficient, 11.7% (9/77) for p53-mutant, and 61.0% (47/77) for no specific molecular profile. The clinicopathological characteristics of each subtype were compared. The p53-mutant and no specific molecular profile subgroups were associated with higher International Federation of Gynecology and Obstetrics stage and International Federation of Gynecology and Obstetrics grade, deeper myometrial invasion, lymphovascular space invasion, lymph node metastasis, and absence of tumor-infiltrating lymphocytes, whereas the POLE mutation and MMR deficient subgroups were associated with lower aggressive features and prominent tumor-infiltrating lymphocytes. Progression-free survival showed that the p53-mutant and no specific molecular profile subgroups had a poorer prognosis than the POLE mutation and MMR deficient subgroups. However, lymph node metastasis was an independent factor associated with a higher risk of disease recurrence in multivariate analysis. In conclusion, ECs with MELF patterns can be divided into 4 molecular subtypes with discrepancies in aggressive clinicopathological characteristics and tumor-infiltrating lymphocytes. Molecular classification has clinical significance in a morpho-molecular approach for ECs with MELF patterns.

Ericoid mycorrhizal fungi mediate the response of ombrotrophic peatlands to fertilization: a modeling study.

Ericaceous shrubs adapt to the nutrient-poor conditions in ombrotrophic peatlands by forming symbiotic associations with ericoid mycorrhizal (ERM) fungi. Increased nutrient availability may diminish the role of ERM pathways in shrub nutrient uptake, consequently altering the biogeochemical cycling within bogs. To explore the significance of ERM fungi in ombrotrophic peatlands, we developed the model MWMmic (a peat cohort-based biogeochemical model) into MWMmic-NP by explicitly incorporating plant-soil nitrogen (N) and phosphorus (P) cycling and ERM fungi processes. The new model was applied to simulate the biogeochemical cycles in the Mer Bleue (MB) bog in Ontario, Canada, and their responses to fertilization. MWMmic_NP reproduced the carbon(C)-N-P cycles and vegetation dynamics observed in the MB bog, and their responses to fertilization. Our simulations showed that fertilization increased shrub biomass by reducing the C allocation to ERM fungi, subsequently suppressing the growth of underlying Sphagnum mosses, and decreasing the peatland C sequestration. Our species removal simulation further demonstrated that ERM fungi were key to maintaining the shrub-moss coexistence and C sink function of bogs. Our results suggest that ERM fungi play a significant role in the biogeochemical cycles in ombrotrophic peatlands and should be considered in future modeling efforts.

Bruton tyrosine kinase inhibitors preserve anti-CD19 chimeric antigen receptor T-cell functionality and reprogram tumor micro-environment in B-cell lymphoma.

BACKGROUND AIMS: Combination therapy is being actively explored to improve the efficacy and safety of anti-CD19 chimeric antigen receptor T-cell (CART19) therapy, among which Bruton tyrosine kinase inhibitors (BTKIs) are highly expected. BTKIs may modulate T-cell function and remodel the tumor micro-environment (TME), but the exact mechanisms involved and the steps required to transform different BTKIs into clinical applications need further investigation. METHODS: We examined the impacts of BTKIs on T-cell and CART19 phenotype and functionality in vitro and further explored the mechanisms. We evaluated the efficacy and safety of CART19 concurrent with BTKIs in vitro and in vivo. Moreover, we investigated the effects of BTKIs on TME in a syngeneic lymphoma model. RESULTS: Here we identified that the three BTKIs, ibrutinib, zanubrutinib and orelabrutinib, attenuated CART19 exhaustion mediated by tonic signaling, T-cell receptor (TCR) activation and antigen stimulation. Mechanistically, BTKIs markedly suppressed CD3-ζ phosphorylation of both chimeric antigen receptor and TCR and downregulated the expression of genes associated with T-cell activation signaling pathways. Moreover, BTKIs decreased interleukin 6 and tumor necrosis factor alpha release in vitro and in vivo. In a syngeneic lymphoma model, BTKIs reprogrammed macrophages to the M1 subtype and polarized T helper (Th) cells toward the Th1 subtype. CONCLUSIONS: Our data revealed that BTKIs preserved T-cell and CART19 functionality under persistent antigen exposure and further demonstrated that BTKI administration was a potential strategy for mitigating cytokine release syndrome after CART19 treatment. Our study lays the experimental foundation for the rational application of BTKIs combined with CART19 in clinical practice.

Integrating a Ferroelectric Interface with a Well-Tuned Electronic Structure in Lithium-Rich Layered Oxide Cathodes for Enhanced Lithium Storage.

Li-rich layered oxides (LLOs) are considered promising candidates for new high-energy-density cathode materials for next-generation power batteries. However, their large-scale applications are largely hindered by irreversible Li/O loss, structural degradation, and interfacial side reactions during cycling. Herein, we demonstrate an integration strategy that tunes the electronic structure by La/Al codoping and constructs a ferroelectric interface on the LLOs surface through Bi0.5Na0.5TiO3 (BNT) coating. Experimental characterization reveals that the synergistic effect of the ferroelectric interface and the well-tuned electronic structure can not only promote the diffusion of Li+ and hinder the migration of On- but also suppress the lattice volume changes and reduce interfacial side reactions at high voltages up to 4.9 V vs Li+/Li. As a result, the modified material shows enhanced initial capacities and retention rates of 224.4 mAh g-1 and 78.57% after 500 cycles at 2.0-4.65 V and 231.7 mAh g-1 and 85.76% after 200 cycles at 2.0-4.9 V at 1C, respectively.

Utility of wood ash, paper sludge and biochar for the mitigation of greenhouse gases emissions from acid boreal soils.

Land-use change in the boreal forest region leads to agriculture to be carried out on acid, shallow and low fertility soils. To correct soil fertility and promote crop productivity, manure and inorganic fertilizers are added, increasing the risk for greenhouse gas emissions (GHGE). To reduce the reliance on synthetic soil amendments while taking advantage of locally relevant industrial by-products, wood ash (WA) and paper sludge (SL) have been proposed as soil amendments for a range of soil types. We posited that amending soils with WA, SL and biochar will improve soil health parameters and fertility of boreal soils. Microbial activity resulting to nitrogen losses and availability were assessed. WA had a stronger ameliorative effect on acid boreal soils compared to SL. Both WA and SL increased soil microbial biomass and basal respiration resulting in higher net mineralization and thus significant increases in CO2 emissions. Co-application of urea with WA or SL further increased net mineralization compared to when used independently. Conversely, the biochar's effect was short-lived and not significant. Nevertheless, addition of biochar was shown to reduce CO2 emissions in all cases except in WA amended soils. No significant differences were observed in CH4 emissions across all treatments. WA and SL may improve soil fertility and quality but could also contribute significantly to GHG emissions in acid boreal soils. Further research is recommended to assess the mitigating effect of various biochar feedstocks on GHG emissions when co-applied with WA and SL.

The Role of the Acetylcholine System in Common Respiratory Diseases and COVID-19.

As an indispensable component in human beings, the acetylcholine system regulates multiple physiological processes not only in neuronal tissues but also in nonneuronal tissues. However, since the concept of the "Nonneuronal cholinergic system (NNCS)" has been proposed, the role of the acetylcholine system in nonneuronal tissues has received increasing attention. A growing body of research shows that the acetylcholine system also participates in modulating inflammatory responses, regulating contraction and mucus secretion of respiratory tracts, and influencing the metastasis and invasion of lung cancer. In addition, the susceptibility and severity of respiratory tract infections caused by pathogens such as Mycobacterium Tuberculosis and the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can also correlate with the regulation of the acetylcholine system. In this review, we summarized the major roles of the acetylcholine system in respiratory diseases. Despite existing achievements in the field of the acetylcholine system, we hope that more in-depth investigations on this topic will be conducted to unearth more possible pharmaceutical applications for the treatment of diverse respiratory diseases.

Asymmetric Exchange Interaction Induces Highly Efficient Alkaline Hydrogen Evolution in RhFe Bimetallene.

An RhFe bimetallene with Fe atoms doped into Rh host for efficient hydrogen evolution reaction (HER), is constructed. When two doped Fe atoms occupy neighboring asymmetric spatial positions, their asymmetric exchange interaction drives electron hopping between the dxy orbital of a Fe atom and the dz 2 orbital of its neighboring Fe atom to push the d band center closer to the Fermi level as a result of electronic state reconstruction. The designed bimetallene with thickness of 0.77 nm (5 atomic layers), possesses excellent HER performance. The low overpotentials of 24.4 and 34.6 mV are achieved at the 10 and 100 mA cm-2 current densities in 1 m KOH solution, respectively. An ultra-low Tafel slope of 8.9 mV dec-1 shows that this kind of RhFe bimetallene is of an ultrafast kinetic process. This work provides a strategy for designing HER catalysts with double metal composites.

Heterogeneity of programmed death-ligand 1 expression and infiltrating lymphocytes in paired resected primary and metastatic non-small cell lung cancer.

Metastatic tumors (MTs) may show different characteristics of the immune microenvironment from primary tumors (PTs) in non-small cell lung cancer (NSCLC). The heterogeneity of immune markers in metastatic NSCLC and its associated factors has not been well demonstrated. In this study, 64 surgically resected specimens of paired PTs and MTs were obtained from 28 patients with NSCLC. Multiplex immunofluorescence (mIF; panel including programmed death-ligand 1 (PD-L1), Cytokeratin, CD8, and CD68) was performed on whole sections. The heterogeneity of the immune contexture of PD-L1 expression, infiltrating lymphocytes, and immune-to-tumor cell distances was quantified via digital image analysis. In a quantitative comparison of MTs and corresponding PTs, MTs showed higher PD-L1 expression levels, lower density of CD8+ cytotoxic T lymphocytes (CTLs), and longer spatial distance between CTLs and tumor cells. Subgroup analysis, which associated clinical factors, revealed that the heterogeneity of immune markers was more obvious in extrapulmonary, metachronous, and treated MTs, while fewer differences were observed in intrapulmonary, synchronous, and untreated MTs. In particular, MTs showed significantly higher PD-L1 expression and lower lymphocyte infiltration in metastatic NSCLC with EGFR mutations. Prognosis analysis showed that an increased density of CD8+ CTLs in MTs was associated with better overall survival (OS). Therefore, significant discrepancies in PD-L1 expression and lymphocyte infiltration in metastatic NSCLC are most likely associated with temporal heterogeneity with a history of anti-treatment and correlated with EGFR mutations. The detection of immune markers in re-obtained metastatic specimens may be required for immunotherapy prediction in these patients with metastatic NSCLC.

Artificial intelligence-assisted system for precision diagnosis of PD-L1 expression in non-small cell lung cancer.

Standardized programmed death-ligand 1 (PD-L1) assessment in non-small cell lung cancer (NSCLC) is challenging, owing to inter-observer variability among pathologists and the use of different antibodies. There is a strong demand for the development of an artificial intelligence (AI) system to obtain high-precision scores of PD-L1 expression in clinical diagnostic scenarios. We developed an AI system using whole slide images (WSIs) of the 22c3 assay to automatically assess the tumor proportion score (TPS) of PD-L1 expression based on a deep learning (DL) model of tumor detection. Tests were performed to show the diagnostic ability of the AI system in the 22c3 assay to assist pathologists and the reliability of the application in the SP263 assay. A robust high-performance DL model for automated tumor detection was devised with an accuracy and specificity of 0.9326 and 0.9641, respectively, and a concrete TPS value was obtained after tumor cell segmentation. The TPS comparison test in the 22c3 assay showed strong consistency between the TPS calculated with the AI system and trained pathologists (R = 0.9429-0.9458). AI-assisted diagnosis test confirmed that the repeatability and efficiency of untrained pathologists could be improved using the AI system. The Ventana PD-L1 (SP263) assay showed high consistency in TPS calculations between the AI system and pathologists (R = 0.9787). In conclusion, a high-precision AI system is proposed for the automated TPS assessment of PD-L1 expression in the 22c3 and SP263 assays in NSCLC. Our study also indicates the benefits of using an AI-assisted system to improve diagnostic repeatability and efficiency for pathologists.

Major pathologic response assessment and clinical significance of metastatic lymph nodes after neoadjuvant therapy for non-small cell lung cancer.

For neoadjuvant therapy in patients with non-small cell lung cancer, the major pathologic response of primary tumors may be an assessable and reliable surrogate measure of survival. Few studies have examined the pathologic evaluation of metastatic lymph node responses and their prognostic significance. This retrospective study enrolled 336 patients with non-small cell lung cancer (squamous cell carcinoma, n = 216; adenocarcinoma, n = 120) treated with neoadjuvant therapy including chemotherapy (n = 316) and targeted therapy (adenocarcinoma, n = 20). The treatment response of the primary tumor and lymph node metastases (LNM) were pathologically assessed according to the multidisciplinary recommendations of the International Association for the Study of Lung Cancer. The relationship of overall survival (OS) and disease-free survival (DFS) with the responses of the primary tumor or LNM was analyzed. The optimal cutoff value of the residual viable tumor (%RVT) of the primary tumor was 12% for both OS (P < 0.001) and DFS (P < 0.001). The pathologic assessment identified LNM in 208 patients. The optimal %RVT cutoff value in LNM was 8% for both OS (P = 0.003) and DFS (P < 0.001). The Spearman's rank correlation coefficient between primary tumors and corresponding LNM was 0.487 for %RVT (P < 0.001), which indicated a positive correlation. On multivariable analysis, an RVT of the primary tumor ≤12% was an independent prognostic factor for improved OS (P = 0.024), whereas an RVT of LNM ≤ 8% was an independent prognostic factor for increased DFS (P = 0.018). Furthermore, in the neoadjuvant chemotherapy group, the optimal %RVT cutoff values for OS in patients with squamous cell carcinoma and adenocarcinoma in the primary tumor were 12% and 58%, respectively. Considering its convenience and operability in clinical application, a 10% threshold RVT value can be used for prognostic evaluation of LNM and primary tumors of squamous cell carcinoma histology; further studies are needed to confirm the optimal cutoff value for primary tumors of adenocarcinoma.

Vegetation composition modulates the interaction of climate warming and elevated nitrogen deposition on nitrous oxide flux in a boreal peatland.

Northern peatlands with large organic nitrogen (N) storage have the potential to be N2 O hotspots under climate warming, elevated N deposition, and vegetation composition change caused by climate change. However, the interactions of these three factors and the primary controls on N2 O fluxes in peatlands are not well-known. Here, the three factors were manipulated in a boreal bog in western Newfoundland, Canada for 5 years. We found that warming mitigated the positive N effect on N2 O fluxes in the mid-growing season under intact vegetation owing to the increase of available N uptake by vegetation and less N for N2 O production. In contrast, warming strengthened the N effect on N2 O fluxes in the early growing season under the absence of graminoids or shrubs, which could be attributed to the increase of available carbon and nitrogen for N2 O production. It should be noted that these effects were not observed under the condition of low carbon availability. In addition, gross primary production was found as a critical control on N2 O fluxes under N addition. Our findings emphasize that the interaction of abiotic (warming and elevated nitrogen deposition) and biotic factors (vegetation composition change) on N2 O fluxes should be taken into account in order to project N2 O fluxes in peatland ecosystems accurately.

A Review of Artificial Intelligence in Precise Assessment of Programmed Cell Death-ligand 1 and Tumor-infiltrating Lymphocytes in Non-Small Cell Lung Cancer.

Advances in immunotherapy have increased the need for stratified predictive biomarkers in patients with non-small cell lung cancer. However, precise evaluation of tumor tissue-based immune biomarkers, such as programmed cell death-ligand 1 (PD-L1) and the characteristics of tumor infiltrating lymphocytes (TILs), is a challenge in clinical practice. In recent years, the digitization of whole-slide images of tissue has accelerated the implementation of artificial intelligence (AI) approaches in tumor pathology and provided an opportunity to use AI tools to improve the interpretation of immune biomarkers. This review describes the current challenges in the assessment of PD-L1 scoring and TILs and demonstrates the role of AI in helping pathologists integrate PD-L1 and biomarkers of the tumor immune microenvironment. Computer-aided PD-L1 scoring is highly consistent with pathologists and reduces the variation among interobservers, providing a promising diagnostic tool in pathology clinics. In addition, applications of image analysis algorithms, in combination with multiplex staining, enable in-depth quantitative and spatial analysis of the broader tumor microenvironment. Upon combining digital pathology and AI, an automatic analysis system of PD-L1 and TILs, which was established using a set of digital staining images and deep learning algorithms, might be an effective way to overcome the challenges in the precise assessment of immune biomarkers.

Fluorine Triggered Surface and Lattice Regulation in Anatase TiO2- x Fx Nanocrystals for Ultrafast Pseudocapacitive Sodium Storage.

Sodium-ion batteries (SIBs) have been considered as one of the most promising secondary battery techniques for large-scale energy storage applications. However, developing appropriate electrode materials that can satisfy the demands of long-term cycling and high energy/power capabilities remains a challenge. Herein, a fluorine modulation strategy is reported that can trigger highly active exposed crystal facets in anatase TiO2- x Fx , while simultaneously inducing improved electron transfer and Na+ diffusion via lattice regulation. When tested in SIBs, the optimized fluorine doped TiO2- x Fx nanocrystals exhibit a high reversible capacity of 275 mA h g-1 at 0.05 A g-1 , outstanding rate capability (delivering 129 mA h g-1 at 10 A g-1 ), and remarkable cycling stability with 91% capacity retained after 6000 cycles at 2 A g-1 . Importantly, the optimized TiO2- x Fx nanocrystals are dominated by pseudocapacitive Na+ storage, which can be attributed to the fluorine induced surface and lattice regulation, enabling ultrafast electrode kinetics.

Expression of epithelial-mesenchymal transition regulators TWIST, SLUG and SNAIL in follicular thyroid tumours may relate to widely invasive, poorly differentiated and distant metastasis.

AIMS: To assess the expression of epithelial-mesenchymal transition (EMT) regulators in follicular thyroid tumours. METHODS AND RESULTS: The expression of E-cadherin (E-CAD) and transcription factors TWIST, SLUG and SNAIL in follicular thyroid tumours was examined by immunohistochemistry in tissue samples, including 18 follicular adenomas (FA), 12 minimally invasive follicular thyroid carcinomas (MI-FTC), 16 widely invasive follicular thyroid carcinomas (WI-FTC), 10 poorly differentiated follicular thyroid carcinomas (PDTC) and six anaplastic thyroid carcinomas (ATC). Metastatic tumour tissues from six of these cases were also examined. The results showed an increasing expression trend of EMT regulators in a panel of follicular tumour cases with a spectrum of morphological subtypes from low- to high-risk malignancy. The expression of EMT regulators was higher in the WI-FTC, PDTC and ATC groups but focal and lower in the FA and MI-FTC groups. Different expression intensity of E-CAD and EMT regulators at the tumour centre part and the invasive front (IF) was observed. The loss of E-CAD and expression of EMT regulators was significantly correlated with distant metastasis and vascular invasion (VI) in the well-differentiated follicular carcinoma (WD-FTC), and six tumours of metastatic sites also showed variables positive for EMT regulators. The disease-free survival analysis showed an apparent relationship between the expression of EMT regulators and the tumour disease-free outcomes in WD-FTC. CONCLUSIONS: Our study supported the role of EMT in the development of follicular thyroid carcinoma and indicated that EMT regulatory proteins may play an important role in WD-FTC that are widely invasive and exhibit distant metastasis.

BAMBI regulates macrophages inducing the differentiation of Treg through the TGF-ß pathway in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by continuous flow limitation and the immune system including macrophages and regulatory T lymphocytes (Tregs) is involved in COPD pathogenesis. In our previous study, we investigated that TGF-ß/BAMBI pathway was associated with COPD by regulating the balance of Th17/Treg. However, the role of bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), a pseudoreceptor of TGF-ß signalling pathway, in regulating the immune system of COPD patients has not been fully studied. Hence, we speculate that the pseudoreceptor BAMBI may play roles in the regulation of M2 macrophages to induce the differentiation of CD4+ naïve T cells into Tregs and influence the immune response in COPD. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy nonsmokers (n = 12), healthy smokers (n = 10) and COPD patients (n = 20). Naïve CD4+ T cells and monocytes-induced macrophages were used for coculture assays. The phenotypic characteristics of macrophages and Tregs were determined by flow cytometry. The expression levels of BAMBI and the TGF-ß/Smad pathway members in M2 macrophages were measured by a Western blot analysis. The monocyte-derived macrophages were stimulated with cigarette smoke extract (CSE, concentration of 0.02%) to simulate the smoking process in humans. pCMV-BAMBI was transfected into monocyte-derived M2 macrophages for subsequent co-culture assays and signalling pathway analysis. RESULTS: Our results showed that M2 macrophages could induce the differentiation of Tregs through the TGF-ß/Smad signalling pathway. In addition, monocyte-derived macrophages from COPD patients highly expressed BAMBI, and had a low capacity to induce Tregs differentiation. The expression of BAMBI and the forced expiratory volume in 1 second (FEV1%) were negatively correlated in COPD. Furthermore, overexpression of BAMBI promoted the conversion of M2 macrophages to M1 macrophages via the TGF-ß/Smad pathway. CONCLUSIONS: We demonstrated that BAMBI could promote the polarization process of M2 macrophages to M1 macrophages via the TGF-ß/Smad signalling pathway and that overexpression of BAMBI could decrease the ability of M2 macrophages to induce Treg differentiation. These findings may provide a potential mechanism by which blocking BAMBI could improve immune function to regulate COPD inflammatory conditions.

A hybrid composed of MoS2, reduced graphene oxide and gold nanoparticles for voltammetric determination of hydroquinone, catechol, and resorcinol.

A ternary hybrid composed of molybdenum disulfide (MoS2), reduced graphene oxide (rGO) and gold nanoparticles (AuNPs@MoS2-rGO) was prepared and used for voltammetric detection of hydroquinone (HQ), catechol (CC) or resorcinol (RC). The composition and structure of the hybrid were characterized in detail. The electrochemical behaviors of a glassy carbon electrode (GCE) modified with the hybrid towards the oxidation of HQ, CC, and RC were investigated using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The results revealed 3D MoS2 is active for the catalytic oxidation of these isomers. Additional integration with rGO and AuNPs further improves catalysis due to their synergistic interaction. The enhanced catalysis leads to oxidation of HQ, CC and RC at 0.074 V, 0.178 V, and 0.527 V (vs. Ag/AgCl; by CV) with reduced overpotential (20-100 mV) and 8-fold or 3-fold increased peak current compared to those obtained on MoS2/GCE, or MoS2-rGO/GCE, respectively. Selective detection of one isomer in the presence of the other two was realized by DPV. The linear ranges are 0.1-950 µM, 3-560 µM, and 40-960 µM for HQ, CC, and RC, and the detection limits are 0.04 µM, 0.95 µM, and 14.6 µM, respectively. The sensor also shows good selectivity and displays satisfactory recovery for real sample analysis. Graphical abstract Schematic illustration of the preparation of AuNPs@MoS2-rGO hybrid by hydrothermal growth of MoS2-rGO and subsequent electrodeposition of gold nanoparticles (AuNPs), and its application for selective detection of hydroquinone, catechol and resorcinol by voltammetry.

Morphologic and Immunohistochemical Study of Clear Cell Carcinoma of the Uterine Endometrium and Cervix in Comparison to Ovarian Clear Cell Carcinoma.

Endometrial clear cell carcinoma (ECCC) and clear cell adenocarcinoma of the cervix (CCAC) are uncommon gynecologic cancers that have morphologic and phenotypic features similar to ovarian clear cell carcinoma (OCCC), but the 3 entities may not be completely identical. This study identified the morphologic and phenotypic characteristics and the differences between ECCC and CCAC in comparison to OCCC. The morphologic features of 16 ECCCs, 7 CCACs, and 22 OCCCs are described. The immunoprofiles of hepatocyte nuclear factor (HNF) 1ß, napsin A, estrogen, progesterone, p53, and Ki-67 were assessed. The results confirm that clear cell carcinomas of the gynecologic tract have a similar spectrum of histopathologic features with the exception that ECCCs have focal solid components more often than CCACs and OCCCs and ECCCs have a slightly higher average mitotic index. Similar to OCCCs, both ECCCs and CCACs were positive for HNF1ß and napsin A, and rarely expressed estrogen and progesterone. HNF1ß was a sensitive marker for clear cell carcinoma at all 3 sites. Napsin A was less sensitive in ECCCs than in OCCCs (56.3% vs. 90.9%, P=0.021). The average Ki-67 index was higher in ECCCs than in OCCCs (52.6% vs. 39.1%) in hotspot scoring, and more ECCC cases had a higher expression (56.3% vs. 22.7%). Diffuse p53 expression, which is associated with TP53 mutation, was observed slightly more often in ECCCs than in OCCCs (25% vs. 9.1%). Our findings revealed morphologic and immunophenotypic similarities and differences among different gynecologic clear cell carcinomas, which may help in improving diagnosis and knowledge of CCC in the female genital tract.

Impact of major different variants of papillary thyroid microcarcinoma on the clinicopathological characteristics: the study of 1041 cases.

BACKGROUND: The incidence of papillary thyroid microcarcinoma (PTMC) has been increasing globally in the past few decades. PTMC does not have a distinctive morphology that results in differences in biological behavior. The aim of this study was to classify PTMCs according to the morphological features and explore the relationship with clinicopathological characteristics. Additionally, we sought to evaluate whether different variants of PTMC can be an independent predictor for lymph mode metastasis when considering other risk factors. METHODS: Between December 2014 and December 2015, 1041 PTMC cases undergoing surgical resection at Tianjin Medical University Cancer Institute and Hospital were reviewed retrospectively. Statistical analysis was performed to investigate the independent factors for lymph node metastasis in PTMC. RESULTS: Conventional variant PTMC (CPTMC), follicular variant PTMC (FPTMC), and encapsulated variant PTMC (EnPTMC) were major variants in PTMC, collectively accounting for 96.7% of the entire PTMC cohort.There were significant differences in clinicopathological characteristics among the three major variants. The frequency of aggressive parameters was significantly different among the three variants, including tumor size, minimal extrathyroidal extension (minimal ETE), and lymph node metastasis (all P < 0.05), being highest in CPTMC, lowest in EnPTMC, and intermediate in FPTMC. FPTMC (OR = 0.642, P = 0.003) and EnPTMC (OR = 0.540, P = 0.041) were independent protective factors for lymph node metastasis (LNM). In contrast, male gender (OR = 1.836, P = 0.000), age less than 45 years (OR = 1.457, P = 0.009), tumor size greater than 0.5 cm (OR = 1.453, P = 0.007), calcification (OR = 1.465, P = 0.016), minimal ETE (OR = 1.801, P = 0.001), and multifocality (OR = 1.721, P = 0.000) were independent risk factors for LNM. CONCLUSIONS: The present study demonstrates the distinct biological behaviors of the three major PTMC variants and establishes an aggressive order of CPTMC â‰« FPTMC > EnPTMC. It is necessary to take into consideration variant-related risks and other independent predictors for the determination of lymphadenectomy in patients with PTMC.

Carbon accumulation and sequestration of lakes in China during the Holocene.

Understanding the responses of lake systems to past climate change and human activity is critical for assessing and predicting the fate of lake carbon (C) in the future. In this study, we synthesized records of the sediment accumulation from 82 lakes and of C sequestration from 58 lakes with direct organic C measurements throughout China. We also identified the controlling factors of the long-term sediment and C accumulation dynamics in these lakes during the past 12 ka (1 ka = 1000 cal yr BP). Our results indicated an overall increasing trend of sediment and C accumulation since 12 ka, with an accumulation peak in the last couple of millennia for lakes in China, corresponding to terrestrial organic matter input due to land-use change. The Holocene lake sediment accumulation rate (SAR) and C accumulation rate (CAR) averaged (mean ± SE) 0.47 ± 0.05 mm yr(-1) and 7.7 ± 1.4 g C m(-2)  yr(-1) in China, respectively, comparable to the previous estimates for boreal and temperate regions. The SAR for lakes in the East Plain of subtropical China (1.05 ± 0.28 mm yr(-1) ) was higher than those in other regions (P < 0.05). However, CAR did not vary significantly among regions. Overall, the variability and history of climate and anthropogenic interference regulated the temporal and spatial dynamics of sediment and C sequestration for lakes in China. We estimated the total amount of C burial in lakes of China as 8.0 ± 1.0 Pg C. This first estimation of total C storage and dynamics in lakes of China confirms the importance of lakes in land C budget in monsoon-influenced regions.