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• A matrix structure driven strategy for sparse matrix problems under the heterogeneous computing framework. • A novel parallel algorithm designed for sparse matrix–matrix multiplication problem based on exploit of shared memory. • A GPU-accelerated parallel state estimation algorithm for large-scale power system. The rapid development of the power grid brings more computational burden to the online state monitoring of the power system. State estimation (SE), the key fundamental part as well as the cornerstone of other applications, requires urgent improvement in its computing efficiency. Recently, the graphics processing unit (GPU) provides potentials for computationally intensive tasks. This paper proposes a GPU-based matrix structure driven (MSD) strategy for the Weighted Least Squares (WLS) state estimator. In this scheme, structures of all the sparse matrices are determined on CPU in advance and numerical calculations are completed during each iteration, with carefully-tuned kernels on GPU. Besides, a novel parallel algorithm is designed to tackle the sparse matrix–matrix multiplication (SPMM) problem, where shared memory is exploited to a great extent for performance improvement. Case studies verify the superiority of the framework and results show that the proposed MSD-SE solution is 4.97 times faster than the CPU-based SE solution on a 27723-bus system. [ABSTRACT FROM AUTHOR]

The superimposed foreland basins mainly develop in central-western China, namely the Himalayan foreland basins superimposed on the Indo-China foreland basins. Previous research on hydrocarbon migration predominantly focused on the typical foreland basins and the fore-deep depression of superimposed foreland basins. As a result of multi-superimposition, large hydrocarbon potentials in the slope zones are evaluated, and the hydrocarbon migration shows significant differences with those in the typical foreland basins. Moreover, the hydrocarbon migration models in the slope zone of superimposed foreland basins are poor analyzed. The Chepaizi High in the South Junggar Basin, a typical slope of superimposed foreland basin, has been taken into consideration. Several points have been ascertained. 1) Multistage charging and readjustment events should be the predominant characters. 2) The combination of multi-type sand-bodies, multistage faults and unconformities have formed step- or "Z"-shaped migration pathways spatially. 3) Hydrocarbons migrated from the areas of high oil potential in the fore-deep depression to those of low oil potential in the slope. 4) The migration models of the J 1 b, K 1 q, N 1 s 1 , and N 1 s 2 have been established. Hydrocarbon reservoirs in the slope zones show the shallow accumulation from deep/distal sources with multiple reservoirs vertically and multi-charging and -readjustments chronologically. 5) The areas of (Wells SM3, C53-C90, and CF2), (Wells SM5, C80, and CF13), and (Wells K8, HG4, SM4, and CF2) can be the favorable targets for the J 1 b, K 1 q, and N 1 s, respectively. • Z-shaped and step-shaped composite hydrocarbon migration pathways. • High oil potential located in the fore-deep depression. • Hydrocarbons migrated from the fore-deep depression to the slope. • Multistage migration histories and multistage readjustments in the slope. • Hydrocarbon charged from deep sources and over long distances. [ABSTRACT FROM AUTHOR]

Electrochemiluminescence (ECL) analysis stands out among various analytical methods due to its exceptional sensitivity and accuracy. However, the poor solubility of most ECL probes limits their effectiveness in aqueous environments. To address this challenge, we developed a water-soluble anion-π + ECL luminophore, DPBC-OTS. With its remarkable water solubility and electron transfer characteristics, the study detailed revealed that DPBC-OTS exhibited excellent ECL performance in the infrared region. Additionally, leveraging ion electrostatic interactions, the DPBC-OTS-based ECL system achieved ultrasensitive detection of the organic fluorine pollutant PFOA, with a detection limit as low as 28.9 nM. This study not only enhances ECL performance in aqueous media through the introduction of the anion-π + compound but also highlights the significant potential of ECL in the trace detection of organic fluorine pollutants.

Tartary buckwheat (Fagopyrum tataricum), a functional grain known for its medicinal and nutritional properties, has garnered significant attention due to its high flavonoid content and unique health benefits. Heat stress during the flowering stage can lead to sterility in Tartary buckwheat, resulting in reduced yields. This study investigates the effects of a treatment (30/27 °C for 7 days) on flower development, fertility, stress physiology, and gene expression in Tartary buckwheat, while also validating the efficacy of hormone treatments in alleviating the negative effects of heat stress. The results show that fertilization in Tartary buckwheat typically occurs within 3-5 days post-anthesis. By the 5th day, the stamen length in the heat-treated group was reduced by 13.89% compared to the control, while pistil length increased by 35.44%. Heat stress delayed the pistil stigma's transition into its highly receptive phase and caused a significant reduction in pollen viability by 15.25% after 5 days of treatment. Furthermore, after 7 days of treatment, the levels of H 2 O 2 and O 2 - increased by 44.9% and 37.2%, respectively. However, Tartary buckwheat mitigated the impact of oxidative damage by enhancing the enzymatic activity of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). Transcriptome analysis revealed that heat stress significantly suppressed the expression of genes in hormone signaling pathways, such as indole-3-acetic acid (IAA), gibberellin (GA), and jasmonic acid (JA). Under heat treatment conditions, exogenous hormone application significantly regulated the dynamics of flower development. Specifically, after 3 days of heat treatment, all hormone treatments significantly inhibited the abnormal elongation of stamens, with GA notably suppressing the abnormal elongation of pistils. After 5 days, GA significantly promoted stamen elongation, while IAA and jasmonic acid (JA) significantly inhibited the abnormal elongation of pistils. After 7 days, all three hormone treatments significantly promoted stamen elongation and effectively inhibited abnormal pistil growth. These results suggest that under heat stress conditions, GA plays a key role in promoting stamen elongation, while IAA and JA inhibit the abnormal elongation of the pistil. Prolonged high temperatures can impair the function of floral organs, while JA treatment on the seventh day of heat treatment effectively restored pistil receptivity and significantly improved pollen vitality. In summary, this study provides in-depth insights into the mechanisms by which heat stress affects flower development in Tartary buckwheat, offering theoretical foundations and practical guidance for reducing the impact of heat stress on buckwheat yield., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Masson SAS. All rights reserved.)

Objective: To investigate the application and clinical significance of different memory phenotypes of γδ T-cell subsets in the clinical diagnosis of pulmonary tuberculosis., Methods: In total, 42 patients with tuberculosis (TB) according to the diagnostic criteria for tuberculosis (WS288-2017) who were treated at the Infectious Diseases Hospital affiliated with Soochow University from February 2023 to July 2023 were enrolled. Additionally, 16 patients with latent TB infection (LTBI) and 20 healthy controls (HCs) were included. Flow cytometry was used to measure the expression levels of γδ T cells, Vδ1 T-cell subsets/Vδ2 T-cell subsets, naive (CD45RA + CD27 + ) cells, central memory (CD45RA-CD27 + ) cells, effector memory (CD45RA-CD27 - ) cells, and terminally differentiated (CD45RA + CD27 - ) cells in the peripheral blood. The expression levels at different stages of TB infection were compared., Results: There were no significant differences in peripheral blood γδ T cells or Vδ1 T cells among the HC, LTBI and TB groups. The proportion of CD45RA-CD27+Vδ2 T cells in TB patients was significantly lower than that in HCs and LTBI patients, but the proportion of CD45RA + CD27-Vδ2 T cells was greater. ROC curve analysis revealed that CD45RA-CD27+Vδ2 T cells (AUC), CD45RA + CD27-Vδ2 T cells (AUC), and the combination of both (AUC) were effective in differentiating TB patients from LTBI patients., Conclusion: The proportions of CD45RA-CD27+Vδ2 T cells and CD45RA + CD27-Vδ2 T cells are potential biomarkers for the diagnosis of active TB infection and are helpful for distinguishing active TB infection from LTBI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

In this manuscript, an efficient self-reinforcing technology-solid hot drawing (SHD) technology-was combined with green processing supercritical carbon dioxide (SC-CO 2 ) foaming technology to promote poly (l-lactic acid) (PLLA) to form an oriented micropore structure. In addition, Polydimethylsiloxane (PDMS), with a high affinity of CO 2 and biological safety, was introduced to enhance the nucleation effect in SC-CO 2 foaming and co-regulate the uniformity of oriented micropores' structure. The results showed that orientation induced PLLA crystallization, so the tensile strength was improved; the maximum tensile strength of the oriented micropores' PLLA reached 151.2 MPa. Furthermore, the micropores mainly improved the toughness; the maximum elongation at break reached 148.3%. It is worth mentioning that PDMS can form an antibacterial film on the surface of the material, so that the material has a continuous antibacterial effect.

Introduction: Pulmonary tuberculosis (PTB) remains one of the deadliest infectious diseases. Understanding PTB immunity is of potential value for exploring immunotherapy for treating chemotherapy-resistant PTB. CD4 + CD25 + Foxp3 + regulatory T cells (Tregs) are key players that impair immune responses to Mycobacteria tuberculosis (MTB). Currently, the intrinsic factors governing Treg expansion and influencing the immunosuppressive attributes of Tregs in PTB patients are far from clear., Methods: Here, we employed flow cytometry to determine the frequency of Tregs and the expression of B and T lymphocyte attenuator (BTLA) and its ligand, herpesvirus entry mediator (HVEM), on Tregs in patients with active PTB. Furthermore, the expression of conventional T cells and of programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) on Tregs in patients with active PTB was determined. We then examined the characteristics of BTLA/HVEM expression and its correlation with Treg frequency and PD-L1 and PD-1 expression on Tregs in PTB patients., Results: The frequency of Tregs was increased in PTB patients and it had a relevance to PTB progression. Intriguingly, the axis of cosignal molecules, BTLA and HVEM, were both downregulated on the Tregs of PTB patients compared with healthy controls (HCs), which was the opposite of their upregulation on conventional T cells. Unexpectedly, their expression levels were positively correlated with the frequency of Tregs, respectively. These seemingly contradictory results may be interpreted as follows: the downregulation of BTLA and HVEM may alleviate BTLA/HVEM cis -interaction-mediated coinhibitory signals pressing on naïve Tregs, helping their activation, while the BTLA/HVEM axis on effector Tregs induces a costimulatory signal, promoting their expansion. Certainly, the mechanism underlying such complex effects remains to be explored. Additionally, PD-L1 and PD-1, regarded as two of the markers characterizing the immunosuppressive attributes and differentiation potential of Tregs, were upregulated on the Tregs of PTB patients. Further analysis revealed that the expression levels of BTLA and HVEM were positively correlated with the frequency of PD-1 + Tregs and PD-L1 + Tregs, respectively., Conclusion: Our study illuminated distinct characteristics of BTLA/HVEM axis expression on Tregs and uncovered its impact on the expansion and attributes of Tregs in patients with active PTB. Therefore, blockade of the BTLA/HVEM axis may be a promising potential pathway to reduce Treg expansion for the improvement of anti-MTB immune responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tang, Shen, Gao, Zhang, Feng, Zhang, Huang and Wang.)

The excellent photophysical and electrochemical properties of porphyrins have inspired widespread interest in the realm of electrochemiluminescence (ECL). The aggregation-caused deficiency of ECL emission in aqueous solution, however, still severely impedes further applications. Herein, a molecule with a donor-acceptor (D-A) configuration, ATPP-Cou, consisting of monoaminoporphyrin as an electron donor and coumarin as an electron acceptor, was designed as an ECL luminophore to address the susceptibility of the porphyrin to aggregation-caused quenching (ACQ) in aqueous solution. ATPP-Cou demonstrated a three-fold enhanced ECL signal compared to pristine ATPP. Despite the acknowledged significance of intramolecular charge transfer (ICT) in generating excited states in ECL, there is a lack of quantitative descriptions. Herein, intensity-modulated photocurrent spectroscopy (IMPS) and scanning photoelectrochemical microscopy (SPECM) were utilized to validate the influence of ICT on the enhancement performance of D-A type ECL molecules. Additionally, ATPP-Cou was also developed as a probe for the successful detection of Cu 2+ in aqueous solution. The present study not only enriches the repertoire of efficient porphyrin-based ECL luminophores applicable in aqueous environments but also exemplifies the successful integration of novel measurement techniques to provide more comprehensive insights into the underlying mechanisms responsible for improved ECL performance., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Cytochromes P450 (P450s or CYPs) are the most important phase I metabolic enzymes in the human body and are responsible for metabolizing ∼75% of the clinically used drugs. P450-mediated metabolism is also closely associated with the formation of toxic metabolites and drug-drug interactions. Therefore, it is of high importance to predict if a compound is the substrate of a given P450 in the early stage of drug development. In this study, we built the multitask learning models to simultaneously predict the substrates of five major drug-metabolizing P450 enzymes, namely, CYP3A4, 2C9, 2C19, 2D6, and 1A2, based on the collected substrate data sets. Compared to the single-task model and conventional machine learning models, the multitask fingerprints and graph neural networks model achieved superior performance with the average AUC values of 90.8% on the test set. Notably, the multitask model demonstrated its good performance on the small amount of substrate data sets such as CYP1A2, 2C9, and 2C19. In addition, the Shapley additive explanation and the attention mechanism were used to reveal specific substructures associated with P450 substrates, which were further confirmed and complemented by the substructure mining tool and the literature.

The development of dual linkage covalent organic frameworks (DL-COFs) is fundamentally important for creating diversified structures and functions. Herein, imine-hydrazone DL-COFs were synthesized for the first time. Three novel imine-hydrazone DL-COFs have been constructed with bifunctional molecule 4-amino-2-methoxybenzohydrazide as the key building block via imine and hydrazone condensations simultaneously.

This article reports a case of mediastinal lymph node tuberculosis with no obvious symptoms and a concealed focus. This patient, a 33-year-old male, suffered from pain behind the sternum after eating. He underwent three gastroscopic examinations and two fine needle punctures guided by ultrasound gastroscopy but was not diagnosed. Chest-enhanced CT revealed a mediastinal mass compressing the adjacent esophagus, suggesting the possibility of enlarged lymph nodes. Furthermore, T cells from patients infected with tuberculosis tested positive. Ultrasound bronchoscopy revealed enlarged lymph nodes in area 7, and then EBUS-TBNA was performed in that region. Only a few scattered lymphocytes and necrotic tissue were found under the biopsy microscope. The EBUS-TBNA biopsy Xpert MTB/RIF showed low positive results, and the EBUS-TBNA puncture fluid Xpert MTB/RIF was positive. Therefore, he was diagnosed with mediastinal lymph node tuberculosis. After antituberculosis treatment with the 2HREZ/10HRE regimen, the patient's pain behind the sternum gradually alleviated, and the enlarged mediastinal lymph nodes gradually narrowed., Competing Interests: The author reports no conflicts of interest in this work., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Artificial enzymes with high stability, adjustable catalytic activity, controllable preparation, and good reproducibility have been widely studied. Noble metal nanozymes, particularly gold nanoparticles (Au NPs), exhibit good catalytic activity, but their stability is poor. In this study, zeolitic imidazolate framework-8 (ZIF-8) was used as a carrier for Au NPs, thus improving the utilization efficiency and conservation stability of the nanozymes. A ZIF-8/Au nanocomposite with peroxidase activity and a raspberry-shaped structure was synthesized. In the assay, ZIF-8/Au catalyzed the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to a blue product oxidized TMB (oxTMB). Glutathione (GSH) selectively inhibited this reaction, with a detection limit of 0.28 µM and linear range of 0.5-60 µM. Using the photo and chromaticity analysis functions, we developed a portable analysis method using a smartphone equipped with a camera module as a detection terminal for a wide range of rapid screening techniques for GSH. Preparation of raspberry-shaped ZIF-8/Au improved the catalytic activity of Au NPs and good results were demonstrated in serum, which suggests their promising application under physiological conditions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Cytochrome P450 (CYP) enzymes are involved in the metabolism of approximately 75% of marketed drugs. Inhibition of the major drug-metabolizing P450s could alter drug metabolism and lead to undesirable drug-drug interactions. Therefore, it is of great significance to explore the inhibition of P450s in drug discovery. Currently, machine learning including deep learning algorithms has been widely used for constructing in silico models for the prediction of P450 inhibition. These models exhibited varying predictive performance depending on the use of machine learning algorithms and molecular representations. This leads to the difficulty in the selection of appropriate models for practical use. In this study, we systematically evaluated the conventional machine learning and deep learning models for three major P450 enzymes, CYP3A4, CYP2D6, and CYP2C9 from several perspectives, such as algorithms, molecular representation, and data partitioning strategies. Our results showed that the XGBoost and CatBoost algorithms coupled with the combined fingerprint/physicochemical descriptor features exhibited the best performance with Area Under Curve (AUC)  of 0.92, while the deep learning models were generally inferior to the conventional machine learning models (average AUC reached 0.89) on the same test sets. We also found that data volume and sampling strategy had a minor effect on model performance. We anticipate that these results are helpful for the selection of molecular representations and machine learning/deep learning algorithms in the P450 model construction and the future model development of P450 inhibition., (© 2024 John Wiley & Sons Ltd.)

Cytochrome P450 3A4 (CYP3A4) is one of the most important drug-metabolizing enzymes in the human body and is well known for its complicated, atypical kinetic characteristics. The existence of multiple ligand-binding sites in CYP3A4 has been widely recognized as being capable of interfering with the active pocket through allosteric effects. The identification of ligand-binding sites other than the canonical active site above the heme is especially important for understanding the atypical kinetic characteristics of CYP3A4 and the intriguing association between the ligand and the receptor. In this study, we first employed mixed-solvent molecular dynamics (MixMD) simulations coupled with the online computational predictive tools to explore potential ligand-binding sites in CYP3A4. The MixMD approach demonstrates better performance in dealing with the receptor flexibility compared with other computational tools. From the sites identified by MixMD, we then picked out multiple sites for further exploration using ensemble docking and conventional molecular dynamics (cMD) simulations. Our results indicate that three extra sites are suitable for ligand binding in CYP3A4, including one experimentally confirmed site and two novel sites.

Competing Interests: The authors have no funding or conflicts of interest to disclose.

Exploring novel electrochemiluminescence (ECL) molecules with high efficiency and good stability in aqueous solutions is crucial for achieving highly sensitive detection of analytes. However, developing chiral luminophores with efficient ECL performance is still a challenge. Herein, we first uncover that artemisinin (ART), a well-known chiral antimalarial drug, features a strong ECL emission at 726 nm with the assistance of a co-reactant potassium persulfate (K 2 S 2 O 8 ), and an ECL efficiency of 195.3%, compared to that of standard Ru(bpy) 3 Cl 2 /K 2 S 2 O 8 . Mechanistic studies indicate that the strong ECL signal of ART is generated when the excited state formed by the reduction of ART peroxide bonds and combination with persulfate returns to the ground state. Significantly, we found that the ECL sensor based on chiral ART could efficiently identify and detect chiral cysteine (Cys) through ECL signals, with a lower limit of detection of 3.7 nM for l-Cys. Density functional theory calculations and scanning electrochemical microscopy technology further confirm that the disparity in the ECL signals is attributed to the different affinity between chiral ART and d/l-Cys, resulting in distinct electron transfer rates. The study demonstrates a new role of ART in ECL investigation and for the first time, achieves the development of ART for the enantioselective recognition and sensitive detection of chiral substances. This will be of vital significance for ECL and chirality research., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Nuclear Dbf2-related kinase 1 (NDR1) is a nuclear Dbf2-related (NDR) protein kinase family member, which regulates cell functions and participates in cell proliferation and differentiation through kinase activity. NDR1 regulates physiological functions by interacting with different proteins. Protein-protein interactions (PPIs) are crucial for regulating biological processes and controlling cell fate, and as a result, it is beneficial to study the actions of PPIs to elucidate the pathological mechanism of diseases. The previous studies also show that the expression of NDR1 is deregulated in numerous human cancer samples and it needs the context-specific targeting strategies for NDR1. Thus, a comprehensive understanding of the direct interaction between NDR1 and varieties of proteins may provide new insights into cancer therapies. In this review, we summarize recent studies of NDR1 in solid tumors, such as prostate cancer and breast cancer, and explore the mechanism of action of PPIs of NDR1 in tumors., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: To assist doctors in making better treatment decisions and improve patient prognosis, it is important to determine which therapy modalities are suitable for various forms of idiopathic hypertrophic cranial pachymeningitis (IHCP)., Methods: All cases were received from the hospital medical record system, and some follow-up information was gathered through telephone follow-up., Results: A total of 26 patients, 14 men and 12 women, with ages ranging from 20 to 73 years and a mean of 47.42 years, were included in the research. Regular types were less likely to recur than irregular and nodular types, focal types were less likely to recur than diffuse types, and corticosteroid-refractory types were more likely to recur than corticosteroid-sensitive types., Conclusions: The extent and shape of the lesion and susceptibility to corticosteroids are potential factors that could influence recurrence. Futhermore, this paper also proposes the fibroblasts as a new therapeutic target which may improve the quality of prognostic survival of patients., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The precisely modulated synthesis of programmable light-emitting materials remains a challenge. To address this challenge, we construct four tetraphenylethylene-based supramolecular architectures (SA, SB, SC, and SD), revealing that they exhibit higher electrochemiluminescence (ECL) intensities and efficiencies than the tetraphenylethylene monomer and can be classified as highly efficient and precisely modulated intramolecular aggregation-induced electrochemiluminescence (PI-AIECL) systems. The best-performing system (SD) shows a high ECL cathodic efficiency exceeding that of the benchmark tris(2,2'-bipyridyl)ruthenium(II) chloride in aqueous solution by nearly six-fold. The electrochemical characterization of these architectures in an organic solvent provides deeper mechanistic insights, revealing that SD features the lowest electrochemical band gap. Density functional theory calculations indicate that the band gap of the guest ligand in the SD structure is the smallest and most closely matched to that of the host scaffold. Finally, the SD system is used to realize ECL-based cysteine detection (detection limit=14.4 nM) in real samples. Thus, this study not only provides a precisely modulated supramolecular strategy allowing chromophores to be controllably regulated on a molecular scale, but also inspires the programmable synthesis of high-performance aggregation-induced electrochemiluminescence emitters., (© 2023 Wiley-VCH GmbH.)

Confinement effects in highly porous nanostructures can effectively adjust the selectivity and kinetics of electrochemical reactions, which can boost the methanol oxidation reaction (MOR). In this work, carbonized ZIF-8-confined hollow PtCo nanospheres (PtCo@carbonized ZIF-8) were fabricated using a facile strategy. A monodisperse confined region was successfully prepared, and the dispersion of the PtCo nanoparticles (NPs) could be precisely regulated, allowing for the effective tuning of the confined region. Thus, the precise regulation of the catalytic reaction was achieved. Importantly, hollow PtCo NPs were prepared using a method based on the Kirkendall effect, and their forming mechanism was systematically investigated. Because of the confinement effects of carbonized zeolitic imidazolate framework-8 (ZIF-8), the crystal and electronic structures of the PtCo NPs were able to be effectively tuned. Our electrochemical results show that PtCo@carbonized ZIF-8 composites manifest a higher mass activity (1.4 A mg Pt -1 ) and better stability compared to commercial Pt/C.

Bismuth vanadate (BiVO 4 ) has been considered a promising photoactive material in photoelectrochemical (PEC) water-splitting systems. However, the performance of BiVO 4 -based photoanodes is currently unsatisfactory, indicating the need for new architectural designs to improve their efficiency. In this paper, a porphyrin-phosphazene polymer (THPP-HCCP) was synthesized with a sizeable conjugated structure, and Ag particles were deposited on its surface as an organic-inorganic composite interface improvement layer. The deposition of the composite polymer film on BiVO 4 resulted in a significant increase in photocurrent density, reaching up to 2.2 mA cm -2 (1.23 V vs. RHE), almost three times higher than pristine BiVO 4 , which benefits from the synergistic effect of Ag nanoparticles and porphyrin-phosphazene. Furthermore, photophysical and intensity-modulated photocurrent analysis demonstrated that the Ag-THPP-HCCP heterostructures could broaden the light-absorbing range and facilitate hole transfer to the semiconductor surface, resulting in an improved water oxidation process. The dynamic charge transport behavior of Ag-THPP-HCCP/BiVO 4 was investigated using scanning photoelectrochemical microscopy, which showed that the rate constant ( K eff ) exhibits an almost 4-fold increase compared to pristine BiVO 4 , indicating a significant improvement in the transport of photogenerated holes. This experiment presents a novel strategy for designing high-efficiency polymer-based photoanodes.

Purpose: To investigate the factors influencing the volume of the olfactory bulb (OB) in patients with post-viral olfactory dysfunction (PVOD)., Methods: We collected 92 olfactory bulb volumes from patients with PVOD who underwent a sinus computed tomographic and magnetic resonance imaging (MRI) scan of the head and collected clinical information including gender, age, disease course, minimal cross-sectional area, nasal airway resistance, and olfactory function. OB volume was measured in MRI and the scans were evaluated according to the Lund-Mackay (LM) scoring system., Results: Male patients with PVOD had a larger OB volume (β = 0.284, P < 0.05). OB volume was smaller in patients with a longer course of olfactory dysfunction (β = - 0.254, P < 0.05). According to the LM scoring system, patients with a higher anterior ethmoidal sinus score had smaller OB volume (β = - 0.476, P < 0.05)., Conclusions: The study revealed that gender, disease course, and the score of anterior ethmoidal sinusitis can affect the OB volume in patients with PVOD., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bladder cancer is the second most prevalent urological malignancy. It's a big contributor to cancer-related deaths throughout the globe. Researchers discovered that the hedgehog signaling (HhS) pathway contributed to the onset and spread of many different kinds of cancer. Nevertheless, the present understanding of the function of HhS in the bladder cancer molecular landscape is incomplete. Raw data were gotten from the IMvigor210, the Gene Expression Omnibus, and The Cancer Genome Atlas databases. Bioinformatics was used to examine the HhS score of each sample, and the enrichment of differentially expressed genes (DEGs), differentiation characteristics, immunological infiltration, and metabolic activity. The HhS prognostic signature was developed with significant assistance from the least absolute shrinkage and selection operator regression and Cox regression. An HhS-related nomogram was developed to assist in the prediction of patients' survival probability. We found that HhS was linked to poor prognosis in bladder cancer, and its activation was linked to the Basal subtype of bladder cancer. Bladder cancer with high HhS activity has higher glycolysis, nucleotide metabolism, amino acid metabolism, and other cancer-promoting metabolic activities. Furthermore, HhS mediates an immunosuppressive microenvironment in bladder cancer on the basis that HhS negatively correlates with the CD8 + T cells and correlates positively with immune checkpoints and T cell exhaustion scores. Finally, an HhS-related signature was developed for predicting the prognosis of patients with bladder cancer. Targeting HhS may be a potential therapy choice for bladder cancer., (© 2023. The Author(s).)

Objective: This study aimed to investigate the demographic and clinicopathological characteristics, and survival outcomes of subglottic Squamous Cell Carcinoma (SCC) based on the Surveillance, Epidemiology, and End Results (SEER) database., Methods: Demographic and clinicopathological information, including age, sex, race, tumor size, histologic grade, clinical/TNM stage, tumor invasion extent, Lymph Node Metastasis (LNM) extent, size of metastatic lymph nodes, LNM ratio and treatment data, of 842 subglottic SCC patients diagnosed between 1996 and 2016 were acquired. Kaplan-Meier survival analyses were performed to assess the effects of clinicopathological characteristics, treatment modalities, surgical procedures, and adjuvant therapies on overall survival and cancer-specific survival., Results: Subglottic SCC was more frequent among males aged 60-70 years, with low-grade but locally advanced lesions without local or distant metastases. Age and several primary tumor/LNM related variables were independent risk factors for overall survival and cancer specific survival. Advanced-stage and high-grade disease led to unfavorable prognosis. The most common treatment modality and surgical procedure were surgery plus radiotherapy and total laryngectomy, respectively. Surgery plus radiotherapy provided favorable 5-year survival outcomes, while total laryngectomy had the worst. Surgery plus adjuvant therapy showed better survival outcomes than surgery alone., Conclusion: This study confirmed the rarity of subglottic SCC. Patients with subglottic SCCs suffered poor prognosis especially for those with advanced-stage or high-grade lesions. The prognosis of subglottic SCC remained poor over the years, despite recent progress in cancer therapies. Surgery plus adjuvant therapy improved the survival outcome. Although larynx preservation surgery was beneficial for early-stage disease, total laryngectomy was favored for patients with advanced tumors., Level of Evidence: Level 4., (Copyright © 2021 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

The intriguing aggregation-induced emission has recently been applied in the electrochemiluminescence, called aggregation-induced electrochemiluminescence (AIE-ECL), which is conducive to solving the water insolubility and aggregation-caused quenching for most organic luminescence probes. However, AIE-ECL still has the problems of low luminous efficiency and limited practical application. In this work, we disclosed the AIE-ECL properties of 1,2,3-triaryl-substituted indenes containing rigid structures. Experimental and theoretical investigations demonstrated that such a rigid structure could significantly enhance the aromaticity and stability and thereby the luminescence performance of these indenes. Moreover, according to the finding of hydrogen/deuterium exchange for active hydrogen in indene under electrical excitation, ultrasensitive detection for D 2 O in H 2 O was realized by such an indene-based AIE-ECL system. Our research not only provided an attractive strategy to enhance the luminescence property for an AIE-active luminophore but also established a superior sensor toward D 2 O.

Objective: To investigate the role of the supraorbital ethmoidal cell（SOEC） in identifying the frontal sinus ostium（FO） and the anterior ethmoidal artery（AEA） in endoscopic sinus surgery, and to evaluate the clinical significance of a proposed endoscopic classification of AEA. Methods: The clinical data of 116 patients with chronic rhinosinusitis were collected. Thirty-six patients（47 sides） with SOEC and DraftⅡA frontal sinusotomy were included. The radiological-anatomical relationship between SOECs and FO, AEAs were recorded. Endoscopic classification of AEA was proposed according to the relationship between the AEA and the ethmoidal roof（EF）: type 1, the AEA prominence did not extend beyond the lateral one-third of the EF; type 2, that exceed the lateral one-third but not beyond two-thirds of the EF; type 3, that exceed the lateral two-thirds of the EF. Results: The incidence of SOECs was 26.1%（47/180） of the DraftⅡA operating sides. On computed tomography images, seven sides of FO were occupied by supra agger frontal cells or supra bulla frontal cells; the other 40 sides（85.1%） were immediately anterior to the SOECs. The AEAs were 100% located near the posterior margins of SOECs with 6（12.8%） running under the EF and 41（87.2%） low-lying distant from the EF. Under endoscopy, the identification rate of SOECs was 89.4%（42/47）, and five（10.6%） SOECs were not confirmed due to edematous mucosa, bleeding, and other reasons. The identification rate of the AEA was 76.6%（36/47）, of which type 1, type 2 and type 3 accounted for 41.7%（15/36）, 38.9%（14/36） and 19.4%（7/36） respectively. After removing the frontoethmoidal cells, all the FO were located anteriorly or anteromedially to the SOECs. All the identified AEAs were located in the posterior boundary of the SOEC openings at the level of the anterior ethmoidal foramen. Conclusion: The SOEC is a reliable landmark for locating the FO and the AEA in endoscopic sinus surgery. The new endoscopic classification of AEA helps the surgeon dissect the frontoethmoidal region precisely., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Natural killer (NK) cells provide important host defense against herpesvirus infections and influence subsequent T cell control of replication and maintenance of latency. NK cells exhibit phases of expansion, contraction and memory formation in response to the natural mouse pathogen murine cytomegalovirus (MCMV). Innate and adaptive immune responses are tightly regulated in mammals to avoid excess tissue damage while preventing acute and chronic viral disease and assuring resistance to reinfection. Caspase (CASP)8 is an autoactivating aspartate-specific cysteine protease that initiates extrinsic apoptosis and prevents receptor interacting protein (RIP) kinase (RIPK)1-RIPK3-driven necroptosis. CASP8 also promotes death-independent signal transduction. All of these activities make contributions to inflammation. Here, we demonstrate that CASP8 restricts NK cell expansion during MCMV infection but does not influence NK memory. Casp8 -/- Ripk3 -/- mice mount higher NK response levels than Casp8 +/- Ripk3 -/- littermate controls or WT C57BL/6 J mice, indicating that RIPK3 deficiency alone does not contribute to NK response patterns. MCMV m157-responsive Ly49H + NK cells support increased expansion of both Ly49H - NK cells and CD8 T cells in Casp8 -/- Ripk3 -/- mice. Surprisingly, hyperaccumulation of NK cells depends on the pronecrotic kinase RIPK1. Ripk1 -/- Casp8 -/- Ripk3 -/- mice fail to show the enhanced expansion of lymphocytes observed in Casp8 -/- Ripk3 -/- mice even though development and homeostasis are preserved in uninfected Ripk1 -/- Casp8 -/- Ripk3 -/- mice. Thus, CASP8 naturally regulates the magnitude of NK cell responses in response to infection where strong activation signals depend on another key regulator of death signaling, RIPK1. In addition, the strong NK cell response promotes survival of effector CD8 T cells during their expansion. Thus, hyperaccumulation of NK cells and crosstalk with T cells becomes amplified in the absence of extrinsic cell death machinery.

Caspase-8 (CASP8) impacts antiviral immunity in expected as well as unexpected ways. Mice with combined deficiency in CASP8 and RIPK3 cannot support extrinsic apoptosis or RIPK3-dependent programmed necrosis, enabling studies of CASP8 function without complications of unleashed necroptosis. These extrinsic cell death pathways are naturally targeted by murine cytomegalovirus (MCMV)-encoded cell death suppressors, showing they are key to cell-autonomous host defense. Remarkably, Casp8 -/- Ripk3 -/- , Ripk1 -/- Casp8 -/- Ripk3 -/- and Casp8 -/- Ripk3 K51A/K51A mice mount robust antiviral T cell responses to control MCMV infection. Studies in Casp8 -/- Ripk3 -/- mice show that CASP8 restrains expansion of MCMV-specific natural killer (NK) and CD8 T cells without compromising contraction or immune memory. Infected Casp8 -/- Ripk3 -/- or Casp8 -/- Ripk3 K51A/K51A mice have higher levels of virus-specific NK cells and CD8 T cells compared to matched RIPK3-deficient littermates or WT mice. CASP8, likely acting downstream of Fas death receptor, dampens proliferation of CD8 T cells during expansion. Importantly, contraction proceeds unimpaired in the absence of extrinsic death pathways owing to intact Bim-dependent (intrinsic) apoptosis. CD8 T cell memory develops in Casp8 -/- Ripk3 -/- mice, but memory inflation characteristic of MCMV infection is not sustained in the absence of CASP8 function. Despite this, Casp8 -/- Ripk3 -/- mice are immune to secondary challenge. Interferon (IFN)γ is recognized as a key cytokine for adaptive immune control of MCMV. Ifngr -/- Casp8 -/- Ripk3 -/- mice exhibit increased lifelong persistence in salivary glands as well as lungs compared to Ifngr -/- and Casp8 -/- Ripk3 -/- mice. Thus, mice deficient in CASP8 and RIPK3 are more dependent on IFNγ mechanisms for sustained T cell immune control of MCMV. Overall, appropriate NK- and T cell immunity to MCMV is dependent on host CASP8 function independent of RIPK3-regulated pathways.

The magnitude of CD8 T cell responses against viruses is checked by the balance of proliferation and death. Caspase-8 (CASP8) has the potential to influence response characteristics through initiation of apoptosis, suppression of necroptosis, and modulation of cell death-independent signal transduction. Mice deficient in CASP8 and RIPK3 ( Casp8 -/- Ripk3 -/- ) mount enhanced peak CD8 T cell levels against the natural mouse pathogen murine cytomegalovirus (MCMV) or the human pathogen herpes simplex virus-1 compared with littermate control RIPK3-deficient or WT C57BL/6 mice, suggesting an impact of CASP8 on the magnitude of antiviral CD8 T cell expansion and not on contraction. The higher peak response to MCMV in Casp8 -/- Ripk3 -/- mice resulted from accumulation of greater numbers of terminally differentiated KLRG1 hi effector CD8 T cell subsets. Antiviral Casp8 -/- Ripk3 -/- T cells exhibited enhanced proliferation when splenocytes were transferred into WT recipient mice. Thus, cell-autonomous CASP8 normally restricts CD8 T cell proliferation following T cell receptor activation in response to foreign antigen. Memory inflation is a hallmark quality of the T cell response to cytomegalovirus infection. Surprisingly, MCMV-specific memory inflation was not sustained long-term in Casp8 -/- Ripk3 -/- mice even though these mice retained immunity to secondary challenge. In addition, the accumulation of abnormal B220 + CD3 + T cells in these viable CASP8-deficient mice was reduced by chronic MCMV infection. Combined, these data brings to light the cell death-independent role of CASP8 during CD8 T cell expansion in mice lacking the confounding impact of RIPK3-mediated necroptosis., Competing Interests: The authors declare no conflict of interest.

Background: ZBED1 (zinc finger BED-type containing 1) is a transcription factor. However, its expression, role and clinical significance in cancer are unclear. The purpose of this study is to investigate the expression of ZBED1 and its effect on the proliferation of gastric cancer (GC)., Methods: Quantitative PCR was used to detect the mRNA level of ZBED1 in GC tissues and normal gastric tissues. Proliferation and colony formation assays were conducted when ZBED1 was expressed ectopically or silenced by constructed vectors. Moreover, chemotherapy-drug induced apoptosis rates were examined by flow cytometry when ZBED1 was expressed ectopically or silenced., Results: The mRNA level of ZBED1 was significantly elevated in 10 out of 11 cases of GC tumor tissue specimens. Results of our analysis derived from a public clinical microarray database suggest that a high expression of ZBED1 predicts a poor outcome. ZBED1 promotes cell proliferation and colony formation. Moreover, ZBED1 decreased the chemosensitivity of GC cells., Conclusions: ZBED1 expression is up-regulated in GC cells. ZBED1 promotes proliferation and decreases the chemosensitivity of GC cells. ZBED1 may be a potential therapeutic target and predictive biomarker in gastric cancer., Competing Interests: None., (IJCEP Copyright © 2018.)

The execution of shock following high dose E. coli lipopolysaccharide (LPS) or bacterial sepsis in mice required pro-apoptotic caspase-8 in addition to pro-pyroptotic caspase-11 and gasdermin D. Hematopoietic cells produced MyD88- and TRIF-dependent inflammatory cytokines sufficient to initiate shock without any contribution from caspase-8 or caspase-11. Both proteases had to be present to support tumor necrosis factor- and interferon-β-dependent tissue injury first observed in the small intestine and later in spleen and thymus. Caspase-11 enhanced the activation of caspase-8 and extrinsic cell death machinery within the lower small intestine. Neither caspase-8 nor caspase-11 was individually sufficient for shock. Both caspases collaborated to amplify inflammatory signals associated with tissue damage. Therefore, combined pyroptotic and apoptotic signaling mediated endotoxemia independently of RIPK1 kinase activity and RIPK3 function. These observations bring to light the relevance of tissue compartmentalization to disease processes in vivo where cytokines act in parallel to execute diverse cell death pathways., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The complex interplay between caspase-8 and receptor-interacting protein (RIP) kinase RIP 3 (RIPK3) driving extrinsic apoptosis and necroptosis is not fully understood. Murine cytomegalovirus triggers both apoptosis and necroptosis in infected cells; however, encoded inhibitors of caspase-8 activity (M36) and RIP3 signaling (M45) suppress these antiviral responses. Here, we report that this virus activates caspase-8 in macrophages to trigger apoptosis that gives rise to secondary necroptosis. Infection with double-mutant ΔM36/M45mutRHIM virus reveals a signaling pattern in which caspase-8 activates caspase-3 to drive apoptosis with subsequent RIP3-dependent activation of mixed lineage kinase domain-like (MLKL) leading to necroptosis. This combined cell death signaling is highly inflammatory, greater than either apoptosis induced by ΔM36 or necroptosis induced by M45mutRHIM virus. IL-6 production by macrophages is dramatically increased during double-mutant virus infection and correlates with faster antiviral responses in the host. Collaboratively, M36 and M45 target caspase-8 and RIP3 pathways together to suppress this proinflammatory cell death. This study reveals the effect of antiviral programmed cell death pathways on inflammation, shows that caspase-8 activation may go hand-in-hand with necroptosis in macrophages, and revises current understanding of independent and collaborative functions of M36 and M45 in blocking apoptotic and necroptotic cell death responses.

Chordomas are rare, locally invasive tumors with characteristic expression of the T-box transcription factor Brachyury. Little is yet known of the molecular events involved in the development of these tumors. Bone morphogenesis protein 4 (BMP4) signaling, which acts upstream of Brachyury in embryonic development, has been implicated in carcinogenesis in multiple malignancies. To explore the role of the canonical BMP4/SMAD signaling pathway in the pathogenesis of chordoma, we investigated, in 40 skull base chordomas, the expression of three major components of the signaling axis: BMP4, phospho-SMAD5 and SMAD4. Immunostaining revealed positive expression in 70%, 52.5% and 90% of cases, respectively. Eighteen (45%) of patients exhibited concurrent positive expression of these markers, which we defined as "high" expression of the BMP4/SMAD signaling pathway. Interestingly, when we compared the pattern of expression with clinicopathological parameters, we found that high expression of the pathway was more often observed in larger tumors (≥ 4 cm) than smaller ones (P = 0.010), and correlated significantly with dural invasion (P = 0.024). The Kaplan-Meier log-rank test showed that the 5-year overall survival rate for patients with high expression of the pathway was significantly lower than those with low expression (71.4% vs. 90.2%, P = 0.010). In conclusion, our results demonstrate for the first time that overexpression of the BMP4/SMAD signaling pathway could predict poor clinical outcome in skull base chordomas, suggesting activation of this pathway is involved in chordoma pathogenesis.