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As an important kind of clustering protocols in wireless sensor networks (WSNs), LEACH and its variants have been demonstrated to efficiently balance the energy consumption, simplify the routing task and extend the network lifetime. Especially, the multi-hop LEACH type protocols have proved to be effective approaches for high energy efficiency, reliability as well as scalability. However, data transmission in hop-by-hop mode increases the energy consumption and end-to-end delay. In this paper, an improved multi-hop LEACH protocol based on fuzzy logic called IMF-LEACH is proposed, which uses a fuzzy logic controller with residual energy, length of data, and distance to BS as fuzzy descriptors to determine the hop count. Moreover, the hop count is used for each CH to find its optimal next-hop intermediate CH with more residual energy and less number of members. Simulations are conducted in MATLAB to evaluate the performance of the proposed protocol, and the results show that IMF-LEACH maximizes the network lifetime and outperforms its counterparts consistently. &nbsp

Malignant glioma, especially glioblastoma (GBM), has historically been associated with a low survival rate. The hyperactivation of STAT3 played a key role in GBM initiation and resistance to therapy; thus, there is an urgent requirement for novel STAT3 inhibitors. BP-1-102 was recently reported as a biochemical inhibitor of STAT3, but its roles and mechanism in biological behavior of glioma cells were still unclear. In this study, the effects of BP-1-102 on proliferation, apoptosis, invasion and neurosphere formation of glioma cell were investigated. Our results indicated that BP-1-102 inhibited the proliferation of U251 and A172 cells, and their IC50 values were 10.51 and 8.534 μM, respectively. Furthermore, BP-1-102 inhibited the invasion and migration abilities of U251 and A172 cells by decreasing the expression of matrix metallopeptidase 9, and induced glioma cell apoptosis by decreasing the expression of B-cell lymphoma-2. BP-1-102 also inhibited the formation of neurosphere. Mechanically, BP-1-102 reduced the phosphorylation of STAT3 and the p-STAT3's nuclear translocation in glioma cells. Thus, this study herein provided a potential drug for glioma therapy.

A classification system for endocervical adenocarcinoma (ECA) based on high-risk human papillomavirus (HPV) status has been established; however, the immunohistochemical markers distinguishing HPV-independent and HPV-associated ECAs have not been fully described. Here, we aimed to characterize ECA immunopathological features.We evaluated the immunohistochemical profile of CLDN18, CDX2, PAX8, p16, p53, and CEA in 60 ECAs comprising 10 HPV-independent ECAs and 50 HPV-associated ECAs. Both the membranous and nuclear expression levels of CLDN18 were analyzed.Membranous CLDN18 (CLDN18 [M]) was found to be expressed in the mucinous epithelium of all HPV-independent ECAs, including eight gastric-type ECAs (G-ECAs), one endometrioid ECA, and one clear cell ECA, but no nuclear CLDN18 (CLDN18 [N]) expression was detected in HPV-independent ECAs. Among HPV-associated ECAs, CLDN18 (M) expression levels in intestinal-type (I-ECAs) and usual-type ECAs (U-ECAs) were significantly different from those in invasive stratified mucin-producing (iSMILE) carcinomas (p = 0.036). Positive CLDN18 (M) staining was present in 55.6% (5/9) of intestinal-type and 39.4% (13/33) of usual-type ECAs and was not present in iSMILE ECAs. Silva pattern C cancers expressed higher levels of CLDN18 (M) than Silva pattern A and B cancers (p = 0.004), whereas the CLDN18 (N) expression levels in cancers showing Silva pattern A were significantly higher than those in cancers exhibiting Silva patterns B and C (p 0.001).Membranous CLDN18 is expressed in ECAs and is particularly frequently expressed in HPV-independent ECAs, and membranous CLDN18 expression has potential as a therapeutic target. Nuclear staining of CLDN18 is a new immunohistochemical marker for diagnosing Silva pattern A HPV-associated ECAs and is associated with a good prognosis. Further studies should investigate the therapeutic and prognostic significance of membranous and nuclear CLDN18 expression and develop a related test that can be implemented in the clinical evaluation of ECAs.

The SARS-CoV-2 pandemic is currently causing an unprecedented global health emergency since its emergence in December 2019. In December 2021, the FDA granted emergency use authorization to nirmatrelvir, a SARS-CoV-2 main protease inhibitor, for treating infected patients. This peptidomimetic is designed with a nitrile warhead, which forms a covalent bond to the viral protease. Herein, we investigate nirmatrelvir analogs with different warheads and their inhibitory activities. In addition, antiviral activities against human alphacoronavirus 229E was also investigated along with a cell-based assay. We discovered that the hydroxymethylketone and ketobenzothiazole warheads were equipotent to the nitrile warhead, suggesting that these analogs can also be used for treating coronavirus infections.

Kernel size, one of the traits that determine wheat yield, is controlled by multiple quantitative trait loci. Polish wheat (Triticum polonicum) has elongated and plump kernel and is a valuable material for breeding high-yielding wheat cultivars. However, genes or loci determining kernel length (KL) in Polish wheat are unknown. We identified and validated a major KL gene, KL-PW, at the P1 locus in Polish wheat. KL-PW is VRT-A2, which encodes a MIKC-type MADS-box protein (MADS55). An insertion/deletion mutation in intron 1 of VRT-A2PW led to an alternatively spliced transcript, VRT-A2PW2. Quantitative PCR analysis showed that VRT-A2PW was more highly expressed in developing seeds than was VRT-A2Ailanmai. Brassinosteroid (BR) sensitivity experiment and the expression of BR-related genes indicated that VRT-A2PW functions as a positive regulator of BR responses. VRT-A2PW significantly increased KL of wheat. These findings not only reveal the molecular basis of KL-PW in controlling KL, but also provide a valuable genetic resource for increasing kernel size in wheat.

Purpose: We have developed a PEGylated transferrin-conjugated liposomes (PTf-Ls) system for the combined tumor imaging and targeted delivery of the IFN-γ–inducible protein-10 (IP-10) gene in a single macromolecular construct. Here, we characterize and analyze the use of this system in a mouse model of breast cancer.Experimental Design: The biophysical and cell transfection properties of PTf-Ls were determined through a series of in vitro experiments. A nude mouse/breast cancer cell line xenograft model (mouse xenograft model) was used to image the tumor internalization of fluorescently labeled PTf-Ls. The clinical use of the system was tested by treating tumor-bearing mice with PTf-Ls loaded with IP-10 plasmid DNA or fluorescent lipoplexes.Results: The resulting 165-nm liposomes (zeta potential = −10.6 mV) displayed serum resistance, low cytotoxicity (in vivo fluorescence and bioluminescence analyses. Tumor fluorescence increased gradually up to 26 hours, whereas background fluorescence decreased to near-baseline levels. Treatment of mice with PTf-Ls entrapped pcDNA3.1-IP-10 suppressed tumor growth in mice by 79% on day 50 and increased the mean survival time of mice. Fluorescent pcDNA-IP-10–entrapped PTf-Ls showed good properties for simultaneous tumor-targeted imaging and gene-specific delivery in an animal tumor model.Conclusions: Our developed transferrin-conjugated liposome system possesses promising characteristics for tumor-targeting, imaging, and gene therapy applications. Clin Cancer Res; 19(15); 4206–17. ©2013 AACR.

Supplementary Figures - PDF file 1800K, Figure S1: Transmission electron microscopy images of P-Ls (A), P-Ls entrapped; Figure S2: High-resolution X-ray photoelectron spectra on nitrogen of Lipid mixture (A), P-Ls (B), PTf-Ls (C) and sulfur atom of PTf-Ls (D); Figure S3: Confocal fluorescence images showing uptake of rhodamine-labeled PTf-Ls by MCF-7 cells. DAPI/nuclei (blue), rhodamine (red); Figure S4: Fluorescence micrographs and differential interference contrast (DIC) images of HeLa cells incubated with PTf-Ls entrapped pEGFP-N1 for 5 h (A), or pretreated for 1 h with 4 microg (B) or 40 microg (C) of transferrin in 1 mL of medium containing 10 % FBS for competition experiment. Images were taken 48 h after transfection; Figure S5: Fluorescence micrographs of HeLa cells transfected with PTf-Ls entrapped pEGFP-N1 (100�x magnification). (A and B) Images taken 48 h after transfection without (A) or with (B) FBS. (C) EGFP expression 24 h after transfection with PTf-Ls entrapped pEGFP-N1 with FBS. (D) EGFP expression 48 h after transfection with PTf-Ls entrapped pEGFP-N1 with FBS; Figure S6: Fluorescence micrographs of HeLa cells incubated with PTf-Ls entrapped pEGFP-N1 for 5 h (I), 24 h (II) or 48 h (III, the transfection medium was changed once at 24 h) (200�x, magnification); Figure S7: Dynamic light scattering particle size distributions for liposomes prepared on 4 June 2011 P-Ls (1) and PTf-Ls (2) or 11 August 2012 P-Ls (2) & PTf-Ls (4), respectively; Figure S8: Cytotoxicity of P-Ls and PTf-Ls measured at 4 h and 24 h after the addition of P-Ls or PTf-Ls to HeLa or MCF-7 cells; Figure S9: Cell cycle profiles of liposome-transfected HeLa cells. Numbers in figure indicate the percentage of cells in each cell cycle phase. Untreated group (A), HeLa cells transfected with P-Ls (B) or PTf-Ls (C)

Supplementary Tables - PDF file 87K, Table S1. Physical properties of liposomes Top: Concentrations of ethanol and Ca2+ for optimized liposome preparation. Bottom: Diameters and surface potentials of P-Ls entrapped pcDNA3.1-IP-10 and PTf-Ls entrapped pcDNA3.1-IP-10 prepared by Method III; Table S2. Chemical composition of liposome surfaces from XPS analysis; Table S3. Serum stability of PTf-Ls entrapped pcDNA3.1-IP-10

Supplementary Methods - PDF file 121K, Supplementary Methods

Objective Gestational diabetes mellitus (GDM) is a serious complication in pregnancy. Despite controlling the plasma glucose levels with dietary intervention (GDM-D) or insulin therapy (GDM-I), children born of diabetic mothers suffer more long-term complications from childhood to early adulthood. Placental circulation and nutrient exchange play a vital role in fetal development. Additionally, placental endothelial function is an indicator of vascular health, and plays an important role in maintaining placental circulation for nutrient exchange. This study was conducted to assess changes in fetal endothelial dysfunction in GDM under different interventions during pregnancy. Methods The primary human umbilical vein endothelial cells (HUVECs) were obtained from normal pregnant women (n = 11), GDM-D (n = 14), and GDM-I (n = 12) patients. LC-MS/MS was used to identify differentially expressed proteins in primary HUVECs among the three groups, after which Bioinformatics analysis was performed. Glucose uptake, ATP level, apoptosis, and differentially expressed proteins were assessed to investigate changes in energy metabolism. Results A total of 8174 quantifiable proteins were detected, and 142 differentially expressed proteins were identified after comparing patients with GDM-D/GDM-I and healthy controls. Of the 142, 64 proteins were upregulated while 77 were downregulated. Bioinformatics analysis revealed that the differentially expressed proteins were involved in multiple biological processes and signaling pathways related to cellular processes, biological regulation, and metabolic processes. According to the results from KEGG analysis, there were changes in the PI3K/AKT signaling pathway after comparing the three groups. In addition, there was a decrease in glucose uptake in the GDM-I (P P Conclusion In summary, endothelial dysfunction occurred in pregnancies with GDM even though the plasma glucose levels were controlled, and this dysfunction might be related to the degree of glucose tolerance. The energy dysfunction might be related to the regulation of the AKT/AMPK/mTOR signaling pathway.

Introduction Myometrial invasion is a prognostic factor for lymph node metastases and decreased survival in non-endometrioid endometrial carcinoma patients. Herein, we explored the mode of myometrial invasion diagnosis in FIGO stage I non-endometrioid carcinoma and evaluated the differences in diagnostic efficiency among intraoperative frozen section (IFS), intraoperative gross examination (IGE), magnetic resonance imaging (MRI), and computed tomography (CT) in clinical practice. Finally, we suggested which test should be routinely performed. Method This was a historical cohort study nationwide with 30 centers in China between January 2000 and December 2019. Clinical data, including age, histology, method of myometrial invasion evaluation (MRI, CT, IGE, and IFS), and final diagnosis of postoperative paraffin sections, were collected from 490 non-endometrioid endometrial carcinoma (serous, clear cell, undifferentiated, mixed carcinoma, and carcinosarcoma) women in FIGO stage I. Results Among the 490 patients, 89.59% presented myometrial invasion. The methods reported for myometrial invasion assessment were IFS in 23.47%, IGE in 69.59%, MRI in 37.96%, and CT in 10.20% of cases. The highest concordance was detected between IFS and postoperative paraffin sections (Kappa = 0.631, accuracy = 93.04%), followed by IGE (Kappa = 0.303, accuracy = 82.40%), MRI (Kappa = 0.131, accuracy = 69.35%), and CT (Kappa = 0.118, accuracy = 50.00%). A stable diagnostic agreement between IFS and the final results was also found through the years (2000–2012: Kappa = 0.776; 2013–2014: Kappa = 0.625; 2015–2016: Kappa = 0.545; 2017–2019: Kappa = 0.652). Conclusion In China, the assessment of myometrial invasion in non-endometrioid endometrial carcinoma is often performed via IGE, but the reliability is relatively low in contrast to IFS. In clinical practice, IFS is a reliable method that can help accurately assess myometrial invasion and intraoperative decision-making (lymph node dissection or not). Hence, it should be routinely performed in non-endometrioid endometrial carcinoma patients.

The Yangtze River Economic Belt (YEB) and the Yellow River Ecological Economic Belt (YREB) surround the two biggest inland rivers and emit the greatest amount of carbon emissions in China. In order to implement China’s dual carbon goal, this research applies a Meta-frontier DN-DEA model, including the carbon reduction factor (CRF), to assess the emission efficiency of energy, CO2, and atmospheric pollutants for a total of 19 regions in YEB and YREB from 2011 to 2017. The synergistic climate risk control efficiency of atmospheric pollutants in the two economic belts are verified by tests for CO2 and three atmospheric pollutants emission elasticity coefficient and Kendall’s coordination coefficient. The results are as follows: First, the overall efficiencies of the two economic belts are both improved by over 30% when subject to CRF. YREB has great potential for carbon emission reduction, and the growth rate of its overall efficiency is higher than that of YEB. Second, YEB’s input term efficiency performs better affected by CRF, while YREB’s environmental pollution control input is insufficient. Third, CO2 and atmospheric pollutants emission efficiencies are significantly improved in YEB, while the environmental regulation of YREB is not obvious for the climate co-benefit of CO2 and atmospheric pollutants. Lastly, high level of climate co-benefit has revealed in YEB during 2011 to 2016, while in 2017 it plummets sharply. Conversely, YREB maintains a stable climate co-benefit.

Background Leucine-rich repeat sequence domains are known to mediate protein‒protein interactions. Recently, some studies showed that members of the leucine rich repeat containing (LRRC) protein superfamily may become new targets for the diagnosis and treatment of tumours. However, it is not known whether any of the LRRC superfamily genes is expressed in the stroma of ovarian cancer (OC) and is associated with prognosis. Methods The clinical data and transcriptional profiles of OC patients from the public databases TCGA (n = 427), GTEx (n = 88) and GEO (GSE40266 and GSE40595) were analysed by R software. A nomogram model was also generated through R. An online public database was used for auxiliary analysis of prognosis, immune infiltration and protein‒protein interaction (PPI) networks. Immunohistochemistry and qPCR were performed to determine the protein and mRNA levels of genes in high-grade serous ovarian cancer (HGSC) tissues of participants and the MRC-5 cell line induced by TGF-β. Results LRRC15 and LRRC32 were identified as differentially expressed genes from the LRRC superfamily by GEO transcriptome analysis. PPI network analysis suggested that they were most enriched in TGF-β signalling. The TCGA-GTEx analysis results showed that only LRRC15 was highly expressed in both cancer-associated fibroblasts (CAFs) and the tumour stroma of OC and was related to clinical prognosis. Based on this, we developed a nomogram model to predict the incidence of adverse outcomes in OC. Moreover, LRRC15 was positively correlated with CAF infiltration and negatively correlated with CD8 + T-cell infiltration. As a single indicator, LRRC15 had the highest accuracy (AUC = 0.920) in predicting the outcome of primary platinum resistance. Conclusions The LRRC superfamily is related to the TGF-β pathway in the microenvironment of OC. LRRC15, as a stromal biomarker, can predict the clinical prognosis of HGSC and promote the immunosuppressive microenvironment. LRRC15 may be a potential therapeutic target for reversing primary resistance in OC.

Background The vast majority of ovarian mucinous carcinomas are metastatic tumours derived from nonovarian primary cancers, typically gastrointestinal neoplasms. Therapy targeting claudin18.2 might be used in gastric, gastroesophageal junction and pancreatic cancers with high expression of claudin18.2. In this study, we aimed to profile the expression of claudin18.2 in primary ovarian mucinous carcinoma (POMC) and metastatic gastrointestinal mucinous carcinoma (MGMC). Methods Immunohistochemistry was used to detect claudin 18.2 expression in whole tissue sections of ovarian mucinous carcinomas, including 32 POMCs and 44 MGMCs, 23 of which were derived from upper gastrointestinal primary tumours and 21 of which were derived from lower gastrointestinal primary tumours. Immunohistochemical studies for claudin18.2, SATB2, PAX8, CK7 and CK20 were performed in all 76 cases. Results Among 76 primary and metastatic mucinous carcinomas, claudin18.2 was expressed in 56.6% (43/76) of cases. MGMCs from the upper gastrointestinal tract, including 22 derived from primary stomach tumours and one derived from a pancreas tumour, were positive for claudin 18.2 in 69.5% (16/23) of cases. MGMCs from the lower gastrointestinal tract, including 10 derived from primary appendiceal cancer and 11 derived from colorectal cancers, showed no claudin18.2 expression (0/21). The expression rate of claudin18.2 in primary ovarian mucinous neoplasms, including 22 primary ovarian mucinous carcinomas and 10 primary ovarian borderline mucinous tumours, was 84.4% (27/32). The common immunophenotypic characteristics of POMCs, upper gastrointestinal tract-derived MGMCs, and lower gastrointestinal tract-derived MGMCs were claudin18.2 + /PAX8 + /SATB2- (17/32), claudin18.2 + /PAX8-/SATB2- (16/23) and claudin18.2-/PAX8-/SATB2 + (19/21), respectively. Conclusion Claudin18.2 is highly expressed in POMCs and MGMCs derived from upper gastrointestinal tract primary tumours; therefore, claudin18.2-targeted therapy might serve as a potential therapeutic strategy for POMCs and MGMCs from the upper gastrointestinal tract.

``Effective robustness'' measures the extra out-of-distribution (OOD) robustness beyond what can be predicted from the in-distribution (ID) performance. Existing effective robustness evaluations typically use a single test set such as ImageNet to evaluate ID accuracy. This becomes problematic when evaluating models trained on different data distributions, e.g., comparing models trained on ImageNet vs. zero-shot language-image pre-trained models trained on LAION. In this paper, we propose a new effective robustness evaluation metric to compare the effective robustness of models trained on different data distributions. To do this we control for the accuracy on multiple ID test sets that cover the training distributions for all the evaluated models. Our new evaluation metric provides a better estimate of the effectiveness robustness and explains the surprising effective robustness gains of zero-shot CLIP-like models exhibited when considering only one ID dataset, while the gains diminish under our evaluation.

The slowing down of Moore's law has driven the development of unconventional computing paradigms, such as specialized Ising machines tailored to solve combinatorial optimization problems. In this paper, we show a new application domain for probabilistic bit (p-bit) based Ising machines by training deep generative AI models with them. Using sparse, asynchronous, and massively parallel Ising machines we train deep Boltzmann networks in a hybrid probabilistic-classical computing setup. We use the full MNIST dataset without any downsampling or reduction in hardware-aware network topologies implemented in moderately sized Field Programmable Gate Arrays (FPGA). Our machine, which uses only 4,264 nodes (p-bits) and about 30,000 parameters, achieves the same classification accuracy (90%) as an optimized software-based restricted Boltzmann Machine (RBM) with approximately 3.25 million parameters. Additionally, the sparse deep Boltzmann network can generate new handwritten digits, a task the 3.25 million parameter RBM fails at despite achieving the same accuracy. Our hybrid computer takes a measured 50 to 64 billion probabilistic flips per second, which is at least an order of magnitude faster than superficially similar Graphics and Tensor Processing Unit (GPU/TPU) based implementations. The massively parallel architecture can comfortably perform the contrastive divergence algorithm (CD-n) with up to n = 10 million sweeps per update, beyond the capabilities of existing software implementations. These results demonstrate the potential of using Ising machines for traditionally hard-to-train deep generative Boltzmann networks, with further possible improvement in nanodevice-based realizations.

Our previous work had demonstrated that UV/NaClO

Objective To establish and validate a predictive formula for calculating the possibility of developing delayed neurological sequelae (DNS) after acute carbon monoxide (CO) poisoning to facilitate better decision-making about treatment strategies. Methods This study retrospectively enrolled 605 consecutive patients who had been newly diagnosed with CO poisoning from the Central Hospital of Enshi Prefecture between January 1, 2015 and December 31, 2020. The cohort was randomly divided into two subgroups: the development cohort (n = 104) and validation cohort (n = 44). Univariate analysis and backward elimination of multivariate logistic regression were used to identify predictive factors, and a predictive formula was established. The performance was assessed using the area under the curve (AUC), the mean AUC of five-fold cross-validation, and calibration plots. Results The formula included four commonly available predictors: initial GCS score, duration of exposure, CK, and abnormal findings on MRI. We next created a formula to calculate the risk score for developing DNS: Risk score = −4.54 + 3.35 * (Abnormal findings on MRI = yes) - 0.51 * (Initial GCS score) + 0.65 * (Duration of exposure) + 0.01 * (CK). Then, the probability of developing DNS could be calculated: Probability of DNS = 1/(1 + e Risk score). The model revealed good discrimination with AUC, and mean AUC of fivefold cross-validation in two cohort, and the calibration plots showed good calibration. Conclusions This study established a prediction predictive formula for predicting developing of DNS, which could facilitate better decision-making about treatment strategies.

The copper phthalocyanine/single-walled carbon nanotube (CuPcI/SWCNT) hybrids were fabricated through doping the CuPc/SWCNT mixture using iodine vapor. It was found that both CuPc and SWCNTs were oxidized by iodine vapor resulting in great increase in carrier concentration. Moreover, the strong π-π conjugation interactions between CuPcI- and I-doped SWCNTs make the CuPcI molecules to assemble on the surface of SWCNTs in an ordered face-on packing, which benefits decreasing the carrier transport barrier across the CuPcI/SWCNT interfaces. The combination of iodine bidoping and the ordered face-on packing of CuPcI on the SWCNT surface realizes the synergetic enhancement of carrier concentration and carrier mobility and therefore the great improvement of electrical conductivity. The maximum electrical conductivity (6281 S cm-1) and thermoelectric power factor (∼304 μW m-1 K-2) at room temperature were obtained at a composition of 60 wt % SWCNTs. The power factor value is 3 orders of magnitude higher than the pure CuPcI and 1 order of magnitude higher than SWCNTs. Consequently, the highest ZT value of CuPc/SWCNT hybrids is up to 0.03, which is among the highest value of organic small-molecule complexes.

Identifying cell subpopulations conferring unfavorable prognosis in cancer holds clinical significance. Here, we sought to identify prognostic cell subsets and develop a novel, prognostic signature for head neck squamous cell carcinoma (HNSCC).Highly prognostic cell subpopulations in HNSCC were identified by integrating single-cell and bulk transcriptomic datasets. The prognostic signature and nomogram were developed by least absolute shrinkage and selection operator and multivariate Cox regression analyses based on significantly upregulated genes in this specific cell subpopulation, respectively. The qRT-PCR experiments were utilized for independent validation in our patient cohort.A specific cancer cell subset associated with unfavorable prognoses was identified. Functional dissections revealed that its transcriptional programs were significantly enriched in E2F, epithelial-to-mesenchymal transition, and glycolysis. A novel prognostic signature comprising six genes was developed and further validated. Risk scores based on qRT-PCR data robustly stratified patients into subgroups with distinct prognoses. A nomogram integrated from this signature and clinical stage had superior performance.Our model derived from integrative analyses of single-cell and bulk RNA-sequencing is a novel, robust prognostic biomarker for HNSCC.

The main objective of this study was to explore the changes in bacterial communities and antibiotic resistance genes (ARGs) in an integrated fixed-film activated sludge (IFAS)+magnetic coagulation process wastewater treatment plant (WWTP) in Xinjiang. The bacterial communities and ARGs in the influent, suspended activated sludge, attached biofilm, and effluent were studied using 16S rRNA gene sequencing and metagenomic sequencing. The results showed that the average relative abundances of Chloroflexi and Nitrospirae in activated sludge were 3.50% and 0.03%, respectively, and their relative abundances in biofilm reached 10.02% and 2.12%, respectively. The average removal rates of NH

The tongue is a complex multifunctional organ that interacts and senses both interoceptively and exteroceptively. Although it is easily visible to almost all of us it is relatively understudied and what is in the literature as regards taste mechanisms is often contradictory or is not comprehensively reported. The tongue is both a motor and a sensory organ: motor in that it is required for speech and mastication, and sensory in that it receives information to be relayed to the central nervous system pertaining to the safety and quality of the contents of the oral cavity. Additionally, the tongue and its taste apparatus form part of an innate immune surveillance system. For example, loss or alteration in taste perception can be an early indication of infection as became evident during the present global SARS-CoV-2 pandemic. Here we particularly emphasize the latest updates in the mechanisms of taste perception, taste bud formation and adult taste bud renewal, the presence, and effects of hormones on taste perception, review the understudied lingual immune system with specific reference to SARS-CoV-2, discuss nascent work on tongue microbiome, as well as addressing the effect of systemic disease on tongue structure and function, especially in relation to taste.

Metal oxides are commonly employed as electron transport layers (ETLs) for n-i-p perovskite solar cells (PSCs), but the presence of surface traps and their mismatched energy alignment with perovskites limits the corresponding device performance. Therefore, the interfacial modification of ETLs by functional molecules becomes an important strategy for tailoring the interfacial properties and facilitating an efficient charge extraction and transport in PSCs. However, an in-depth understanding of the influences of their molecular structures on the surface chemistry and electronic properties of ETLs is rarely discussed. Herein, three carboxylic acid-based molecules with different chemical structures were employed to modify the SnO

Altered glycan levels in serum have been associated with increased risk of cancer. In this study, we have developed and validated a HPLC-based method to analyze monosaccharide composition (D-mannose, Glucosamine, Galactosamine, Glucuronic acid, D-glucose, D-galactose, D-xylose, L-fucose) in human serum, with L-rhamnose, being used as internal standard. Monosaccharides obtained from hydrolyzed serum samples were derivatized by 1-Phenyl-3-methyl-5-pyrazolone. A ZORBAX XDB-C18 column(150×4.6mm) was used for chromatographic separation with 100 mM ammonium acetate buffer (NH4Ac-HAc, PH=5.5, solvent A), acetonitrile (ACN, solvent B) as a mobile phase. The calibration standard curves for the eight monosaccharides showed good linearity over the range of 2.5-500μg/mL with R2 > 0.995. The relative standard deviation values for intra-day and inter-day precision were ≤ 5.49%. Recovery was 69.01-108.96%. We observed that this column exhibited high specificity and selectivity to separate monosaccharides from serum. This method was then applied to quantitatively analyze the serum monosaccharide levels in 30 patients with endometrial cancer and 30 matched healthy controls. Statistical analysis indicated that the serum monosaccharide levels were significantly higher in patients compared with healthy controls (P value< 0.0001). Overall, we report here a simple, reliable, low-cost, and reproducible HPLC method for the separation and quantification monosaccharides in the human serum, which has potential value to serve as a screening marker for endometrial cancer.

Introduction: Myometrial invasion (≤/＞50%) is a prognostic factor for lymph node metastases and decreased survival in non-endometrioid endometrial carcinoma. Our aim was to explore the mode of myometrial invasion diagnosis in FIGO stage I non- endometrioid carcinoma and to evaluate differences of diagnostic efficiency among intraoperative frozen section, gross examination, MRI and CT in clinical practice and to suggest which one should be routinely performed. Method: This is a historical cohort study nationwide (thirty centers in China between January 2000 and December 2019). Clinical data including age, histology, method of myometrial invasion evaluation (MRI, CT, intraoperative gross examination, frozen section) and final diagnosis of postoperative paraffin section were collected from 490 non-endometrioid endometrial carcinoma (serous, clear cell and undifferentiated carcinoma, carcinosarcoma and mixed pathology) women in FIGO stage I. Results: Among the 490 patients, 89.59% were detected with myometrial invasion. The methods reported for myometrial invasion assessment were frozen section in 23.47%, gross examination in 69.59%, MRI in 37.96% and CT in 10.20% of cases. The concordance between intraoperative frozen section and postoperative paraffin section was the highest (Kappa = 0.631, accuracy = 93.04%), followed by gross examination (Kappa = 0.303, accuracy = 82.40%), MRI (Kappa = 0.131, accuracy = 69.35%), and CT (Kappa = 0.118, accuracy = 50.00%). A stable diagnostic agreement between frozen section and final results were found through years (2000–2012 Kappa = 0.776; 2013–2014 Kappa = 0.625; 2015–2016 Kappa = 0.545; 2017–2019 Kappa = 0.652). Conclusion: In China, the assessment of myometrial invasion in non-endometrioid endometrial carcinoma is most often performed with intraoperative gross examination, but the reliability is relatively low in contrast to intraoperative frozen section. In clinical practice, frozen section is a reliable method that can help myometrial invasion accurately assessing and intraoperative decision making (lymph node dissection or not). It should be performed routinely in patients with intrauterine non-endometrioid endometrial carcinoma.

Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability. By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research (ICR) mouse model, we found that a ferroptosis phenomenon may exist. Mice were divided into six groups and administered different doses of bisphenol A via intragastric gavage once daily for 45 consecutive days. Serum was then collected to determine the levels of superoxide dismutase and malondialdehyde. Epididymal sperm was also collected for semen analysis, and testicular tissue was collected for ferritin content determination, electron microscope observation of mitochondrial morphology, immunohistochemistry, real-time quantitative polymerase chain reaction, and western blot analysis. Exposure to bisphenol A was found to decrease sperm quality and cause oxidative damage, iron accumulation, and mitochondrial damage in the testes of mice. In addition, bisphenol A was confirmed to affect the expression of the ferroptosis-related genes, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), cyclooxygenase 2 (COX2), and acyl-CoA synthetase 4 (ACSL4) in mouse testicular tissues. Accordingly, we speculate that bisphenol A induces oxidative stress, which leads to the ferroptosis of testicular cells. Overall, the inhibition of ferroptosis may be a potential strategy to reduce male reproductive toxicity caused by bisphenol A.

Fibrocystin/Polyductin (FPC) is encoded by PKHD1 which, when mutated, causes autosomal recessive polycystic kidney disease (ARPKD). FPC’s function and its role in cystogenesis are unknown. We describe that endogenous FPC undergoes complex proteolytic processing, generating three small C-terminal fragments (ICDs), one of which (ICD15) contains a novel mitochondrial targeting sequence that directs its translocation into mitochondria. Pkhd1 inactivation leads to aberrant ultrastructural morphology of mitochondria in proximal tubules of developing kidneys. FPC inactivation enhances renal cystogenesis and causes severe pancreatic cystogenesis in a Pkd1 mouse mutant with blocked G protein‐coupled receptor proteolysis site (GPS) cleavage of the Pkd1-encoded Polycystin-1 protein. Deletion of the ICD15 region, encoded by exon 67, is sufficient to enhance renal cystogenesis but does not cause pancreatic cystogenesis. Our results connect FPC, a ciliary protein, directly to a mitochondrial signaling pathway whose perturbation is implicated in PKD pathogenesis.

Highly specialized myrmecophagy (ant- and termite-eating) has independently evolved multiple times in species of various mammalian orders and represents a textbook example of phenotypic evolutionary convergence. We explored the mechanisms involved in this unique dietary adaptation and convergence through multi-omic analyses, including analyses of host genomes and transcriptomes, as well as gut metagenomes, in combination with validating assays of key enzymes’ activities, in the species of three mammalian orders (anteaters, echidnas and pangolins of the orders Xenarthra, Monotremata and Pholidota, respectively) and their relatives. We demonstrate the complex and diverse interactions between hosts and their symbiotic microbiota that have provided adaptive solutions for nutritional and detoxification challenges associated with high levels of protein and lipid metabolisms, trehalose degradation, and toxic substance detoxification. Interestingly, we also reveal their spatially complementary cooperation involved in degradation of ants’ and termites’ chitin exoskeletons. This study contributes new insights into the dietary evolution of mammals and the mechanisms involved in the coordination of physiological functions by animal hosts and their gut commensals.

Long-term indwelling catheters or stents often cause complications like infection, encrustation, hematuria, pain, and so on. The source of these problems is bacteria, which can form biofilms on the stents to reduce antibiotic sensitivity and produce urease to form encrustation by increasing the urine pH. Urinary tract infection (UTI) can aggravate the body damage and even seriously endanger lives, and the encrustation will block the stents, which can cause hydronephrosis and renal function damage. Therefore, the prevention of UTI and encrustation represents a great challenge in clinical ureteral stent uses. In this work, a clickable mussel-inspired peptide and antimicrobial peptide (AMP) were used to functionalize the commercial stents' surfaces to inhibit long-term infection and encrustation caused by bacteria. Copper (Cu) ions were used to coordinate the mussel-inspired peptide to improve the stability. The AMP with an azido group was clicked to the mussel-inspired Cu-coordinated peptide coating through click chemistry. The bio-inspired antibacterial coating was constructed with excellent stability, bactericidal properties, and improved biological compatibility. In in vitro and in vivo experiments, it was further found that the coating showed bactericidal and encrustation reduction abilities. This study thus developed an effective, safe, and stable AMP coating on urinary stents/catheters capable of long-term antibacterial and encrustation inhibition.

Wheat grown in cadmium (Cd)-contaminated soils easily accumulates more Cd in edible parts than the Chinese safety limit (0.1 mg/kg). FeCl

Objective Gestational diabetes mellitus (GDM) is a serious pregnancy complication. Even if the plasma glucose levels were controlled with dietary intervention (GDM-D) or insulin therapy (GDM-I), children from diabetes mothers have increased rates of CVD from childhood to early adulthood. Endothelial function is a barometer of vascular health. The study was conducted to find out the changes in fetal endothelial dysfunction in GDM under different interventions in pregnancies. The primary HUVECs were separated from human normal pregnant (n=6), GDM-D (n=6), and GDM-I (n=6), respectively. Methods LC-MS/MS was used to identify differentially expressed proteins of primary HUVECs among the three groups and bioinformatics analysis was then performed. Glucose uptake, ATP level, apoptosis, as well as differentially protein was assessed to identify how the energy metabolism changed. Results A total of 8174 quantifiable proteins were detected, and 142 differentially expressed proteins were found both in comparison between the patients with GDM-D/GDM-I and healthy controls. 64 proteins were upregulated, while 77 were downregulated. Bioinformatics analysis revealed that differentially expressed proteins are involved in multiple biological processes and signaling pathways related to cellular process, biological regulation, and metabolic process. The PI3K/AKT signaling pathway was changed among the three groups. Glucose uptake was decreased in GDM-I (pConclusions In summary, endothelial dysfunctions happened in pregnancies with GDM even though the plasma glucose levels were controlled. The energy dysfunction might be related to the regulation of the AKT/AMPK/mTOR signal pathway.

Unplanned intraoperative hypothermia is a complication that can lead to a variety of negative outcomes, such as cardiovascular events. We aimed to develop and validate an intraoperative hypothermia risk prediction nomogram for patients with colorectal cancer undergoing laparoscopic colorectal procedures. We conducted a prospective cohort study with 1,091 patients (ie, 765 in the training cohort, 326 in the validation cohort) from October 2020 to November 2021. We included six predictors in the nomogram model: body mass index, diabetes diagnosis, ambient temperature, ambient humidity, duration of surgery, and use of a forced-air warmer. The model performed well, and the area under the curve was 0.855. These results, together with an external validation value, mean that health care professionals can use the nomogram to calculate the intraoperative hypothermia risk for patients undergoing laparoscopic colorectal procedures and make clinical decisions based on the results.

Major advances have been made to improve the sensitivity of mass analyzers, spectral quality, and speed of data processing enabling more comprehensive proteome discovery and quantitation. While focus has recently begun shifting toward robust proteomics sample preparation efforts, a high-throughput proteomics sample preparation is still lacking. We report the development of a highly automated universal 384-well plate sample preparation platform with high reproducibility and adaptability for extraction of proteins from cells within a culture plate. Digestion efficiency was excellent in comparison to a commercial digest peptide standard with minimal sample loss while improving sample preparation throughput by 20- to 40-fold (the entire process from plated cells to clean peptides is complete in ~300 min). Analysis of six human cell types, including two primary cell samples, identified and quantified ~4000 proteins for each sample in a single high-performance liquid chromatography (HPLC)–tandem mass spectrometry injection with only 100 – 10,000 cells, thus demonstrating universality of the platform. The selected protein was further quantified using a developed HPLC-multiple reaction monitoring method for HeLa digests with a heavy labeled internal standard peptide spiked in. Excellent linearity was achieved across different cell numbers indicating a potential for target protein quantitation in clinical research.

1. Sneha Butala, MD* 2. Lauren Pronman, DO*,† 3. Michelle Baechtold, MD‡ 4. Timmie R. Sharma, MD‡ 5. Rebecca Fish, MD§ 6. Qin Yao, MD§ 1. *Department of Pediatrics and 2. §Division of Neonatology and Perinatal Medicine, Department of Pediatrics, Rainbow Babies and Children's Hospital, Cleveland, OH 3. †Department of Genetics and Genomics and 4. ‡Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, OH A 24-year-old gravida 2 para 1 woman presents at 32 weeks’ gestation with vaginal bleeding concerning for placental abruption. The prenatal history is unclear because the mother obtained most of her prenatal care in Mexico. She precipitously gives birth to a female infant via breech vaginal delivery. On delivery, the infant is intubated and given 1 dose of surfactant due to respiratory failure. Apgar scores are 2 and 3 at 1 and 5 minutes, respectively. The birthweight is 1,900 g. A chest radiograph demonstrates diffuse severe alveolar opacity in bilateral lung fields consistent with severe respiratory distress syndrome. The infant is transported to a tertiary center and develops worsening hypoxia requiring 100% oxygen. The blood gas on admission reveals severe mixed respiratory and metabolic acidosis. The infant receives additional doses of surfactant and a prolonged period of respiratory support. The severity of the infant’s respiratory distress syndrome is disproportionate to the degree of prematurity. Pertinent physical examination findings include mottling of the skin with thick white scale. The scale is symmetrical, involving the scalp, shoulders, and extremities (Figs 1 and 2). External ear canals are not visible; they may be absent or occluded by the scale, which is also found around the nares. Thin erosions in rectangular shapes on her abdomen are noted where cardiac leads have been placed. Erosions are also found on the right side of the face near the endotracheal tube securement device and on the bilateral dorsum of feet. Auscultation of the lungs reveals coarse breath sounds and diffuse crackles bilaterally, without increased work of breathing, retractions, or nasal flaring. There is no collodion membrane, ectropion (outturning of the eyelids), or eclabium (outturning of the lips) present. Figure 1. Thick adherent scales and erosions on day 1. Figure 2. Thick adherent scales and erosions at 4 weeks. The complete blood …

With the rapid growth of digital music today, due to the complexity of the music itself, the ambiguity of the definition of music category, and the limited understanding of the characteristics of human auditory perception, the research on topics related to automatic segmentation of music is still in its infancy, while automatic music is still in its infancy. Segmentation is a prerequisite for fast and effective retrieval of music resources, and its potential application needs are huge. Therefore, topics related to automatic music segmentation have important research value. This paper studies an improved algorithm based on negative entropy maximization for well-posed speech and music separation. Aiming at the problem that the separation performance of the negative entropy maximization method depends on the selection of the initial matrix, the Newton downhill method is used instead of the Newton iteration method as the optimization algorithm to find the optimal matrix. By changing the descending factor, the objective function shows a downward trend, and the dependence of the algorithm on the initial value is reduced. The simulation experimental results show that the algorithm can separate the source signal well under different initial values. The average iteration time of the improved algorithm is reduced by 26.2%, the number of iterations is reduced by 69.4%, and the iteration time and the number of iterations are both small. Fluctuations within the range better solve the problem of sensitivity to the initial value. Experiments have proved that the new objective function can significantly improve the separation performance of neural networks. Compared with the existing music separation methods, the method in this paper shows excellent performance in both accompaniment and singing in separated music.