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Background and Objectives: Maintenance hemodialysis (MHD) patients are at a higher risk of cardiovascular disease (CVD), a common complication and leading cause of death. Persistent micro-inflammation is a unique feature of MHD. Given the established role of inflammation in the pathogenesis of atherosclerosis, this study aims to explore whether novel inflammatory markers (inflammation index) can serve as independent risk factors for CVD in MHD patients., Methods: A cross-sectional survey was conducted on patients from three dialysis centers, categorized into a CVD and non-CVD group based on medical history, laboratory tests, and physical examination. Fasting blood samples were collected from all participants for indicator testing., Results: The analysis of 209 patients revealed that 104 had concurrent CVD. Patients in the CVD group were significantly older and exhibited higher anxiety and depression scores. Forward stepwise multivariate logistic regression results identified the inflammation index neutrophil-to-lymphocyte ratio (NLR) (OR = 1.27, 95% CI 1.082-1.491, P < 0.05) and systemic immune-inflammation index (SII) (OR = 1.001, 95% CI 1.0001-1.002, P < 0.05) as independent risk factors for CVD in MHD patients. Receiver operating characteristic (ROC) curve analysis demonstrated that SII, platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and NLR all possess predictive diagnostic values for CVD events in this patient population., Conclusions: Hemodialysis centers can utilize simple and cost-effective inflammatory markers to proactively identify patients at risk of CVD. Future research into how inflammation contributes to CVD in MHD is required., Competing Interests: Declarations Ethics approval and informed consent The Ethics Committee of Dongzhimen Hospital, Affiliated with the Beijing University of Chinese Medicine, approved this study (2024DZMEC-313–02), and all enrolled patients signed valid informed consent forms. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The crosstalk between endoplasmic reticulum and mitochondria is of significance in apoptosis, in which cytochrome b 5 (Cyt b 5 ) is thought to be a major target for cytochrome c (Cyt c) upon its release from the mitochondria. In the absence of Cyt b 5 , the role of interactions of Cyt c with CYP-dependent monooxygenase system in apoptotic regulation was explored in this study. NADPH-dependent and Cyt c-induced formation of reactive oxygen species (ROS) and NADPH-independent Cyt c unfolding were revealed. With the aid of a CPR inhibitor and CYP antibodies, the interactions among Cyt c, cytochrome P450 reductase (CPR) and cytochrome P450 (CYP) are evidenced, which are found crucial for monooxygenase-derived ROS formation. The underlying structural basis of Cyt c-CYP complex was unveiled by molecular dynamics simulations. This study provides novel insights into how Cyt c regulates ROS formation through the interactions with CPR and CYP, and is implicated for a deeper understanding of the regulation mechanism in the mitochondria-endoplasmic reticulum apoptotic pathway., 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 Elsevier B.V. All rights reserved.)

This work investigates the observer-based asynchronous boundary stabilization for a kind of stochastic Markovian reaction-diffusion neural networks with exogenous disturbances. Specifically, parameter uncertainties are considered in the drift item. First, a hidden Markov model is introduced that guarantees the observer modes run asynchronously with the system modes. It should be noted that the asynchronous observer constructed in this work only uses the boundary measurement information. Then a nonfragile asynchronous observer-based boundary controller is designed. Taking advantage of inequality techniques and stochastic analysis method, sufficient criterion is provided to satisfy input-to-state exponentially mean-square stability, and the asynchronous boundary observer/controller gains are further derived. As a special case, the synchronous observer-based boundary stabilization is also obtained. Finally, a numerical example is exploited to manifest the validity of the established results.

Exploring the structural basis of membrane proteins is significant for a deeper understanding of protein functions. In situ analysis of membrane proteins and their dynamics, however, still challenges conventional techniques. Here we report the first attempt to immobilize membrane protein complexes on surface-enhanced Raman scattering (SERS)-active supports, titanium dioxide-coated silver (Ag@TiO 2 ) nanoparticles. Biocompatible immobilization of microsomal monooxygenase complexes is achieved through lipid fission and fusion. SERS activity of the Ag@TiO 2 nanoparticles enables in situ monitoring of protein-protein electron transfer and enzyme catalysis in real time. Through SERS fingerprints of the monooxygenase redox centers, the correlations between these protein-ligand interactions and reactive oxygen species generation are revealed, providing novel insights into the molecular mechanisms underlying monooxygenase-mediated apoptotic regulation. This study offers a novel strategy to explore structure-function relationships of membrane protein complexes and has the potential to advance the development of novel reactive oxygen species-inducing drugs for cancer therapy.

In traditional multienzyme random co-immobilization, it is difficult to precisely locate and regulate the relative positions between two enzyme molecules, resulting in low cascade efficiency between the two enzymes and limiting the application of multienzyme cascade catalysis technology. This study prepared PVAC@Y-dsDNA@GOD/HRP magnetic co-immobilized multienzyme by constructing a three-pronged DNA scaffold for co-coupling glucose oxidase (GOD) and horseradish peroxidase (HRP), which achieved directional co-immobilization of dual enzymes and precise regulation of inter-enzyme distance. Compared with traditional random co-immobilization of multienzyme, PVAC@Y-dsDNA@GOD/HRP could shorten the distance between GOD and HRP to the nanoscale and form substrate channeling, which greatly improved the cascade activity between the two enzymes. The inter-enzyme spacing between GOD and HRP could be precisely regulated by changing the length of DNA strands. When the inter-enzyme spacing was 10.08 nm, PVAC@Y-dsDNA@GOD/HRP exhibited high cascade activity of 707 U/mg. The inter-enzyme spacing that was too large or too small would reduce the cascade activity, indicating a distance-dependence of multienzyme cascade activity. PVAC@Y-dsDNA@GOD/HRP showed good reusability, indicating that the three-pronged DNA scaffold constructed by DNA double strands hybridization could firmly immobilize enzyme on carrier, with less enzyme leakage., 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 Elsevier B.V. All rights reserved.)

Obstructive sleep apnea (OSA) leads to chronic intermittent hypoxia (CIH) and is not well addressed by current therapies. The genioglossus (GG) is the largest upper airway dilator controlling OSA pathology, making its repair a potential treatment. This study investigates dental pulp stem cells (DPSCs) in repairing GG injury in a CIH mouse model. We induced DPSCs to myogenic lineage cells (iDPSCs) and transplanted them into GG of CIH mice. DPSCs/iDPSCs grafts improved EMG GG and muscle type transitions while reducing tumor necrosis factor α (TNF-α), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) levels, improving body weight. Moreover, iDPSCs increased Pax7 + /Ki67 + and human-derived STEM121 cells in the GG compared with DPSCs. DPSCs/iDPSCs enhanced Desmin + myotube formation in myoblasts under hypoxia in vitro , with iDPSCs increased human-derived myogenic markers and nuclei in myotubes. These results indicate that iDPSCs, beyond their paracrine effects like DPSCs, directly participate in myogenic differentiation, supporting the potential use of DPSCs for OSA treatment., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Three-dimensional (3D) Na 2 Ti 3 O 7 flower (NTF) systems were synthesized, followed by sputter coating with silver (Ag) nanoparticles to increase surface-enhanced Raman scattering (SERS) activity. By varying the sputtering time, SERS activity of the Ag-decorated NTF (NTF-Ag) structures was optimized. Furthermore, the theoretical evidence from finite difference time domain (FDTD) simulations confirmed that an appropriate density of Ag particles increased the electromagnetic field contribution. The electromagnetic field contribution is high because the special petal-shaped structure can promote multiple reflections and scattering, thus providing efficient resonance absorption for charge-transfer (CT) and exciton enhancements. Highly SERS-active NTF-Ag composites were developed and exploited for the detection of malachite green (MG), a model contaminant in the food industry. The detection limit of this method for MG reached 3.78 × 10 -10 M, with a standard deviation of homogeneity of 6.83 %. This method was successfully applied to detect MG on crucian carp skin, and it showed high recovery, indicating that it can serve as a practical method for MG evaluation. All results demonstrated that the prepared NTF-Ag composite has great potential in the application of SERS-based contamination assessment in the food industry., 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 Elsevier B.V. All rights reserved.)

Membrane proteins are involved in a variety of dynamic cellular processes and exploration of the structural basis of membrane proteins is of significance for a better understanding of their functions. In situ analysis of membrane proteins and their dynamics is, however, challenging for conventional techniques. Surface-enhanced Raman spectroscopy (SERS) is powerful in protein structural characterization, allowing for sensitive, in-situ and real-time identification and dynamic monitoring under physiological conditions. In this review, the applications of SERS in probing membrane proteins are outlined, discussed and prospected. It starts with a brief introduction to membrane proteins, SERS theories and SERS-based strategies that commonly-used for membrane proteins. How to assemble phospholipid biolayers on SERS-active materials is highlighted, followed by respectively discussing about direct and indirect strategies for membrane protein sensing. SERS-based monitoring of protein-ligand interactions is finally introduced and its potential in biomedical applications is discussed in detail. The review ends with critical discussion about current challenges and limitations of this research field, and the promising perspectives in both fundamental and applied sciences., 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 Elsevier B.V. All rights reserved.)

Objective: Maintenance hemodialysis (MHD) patients suffer from enormous physical, mental stress and poor quality of life, so an increasing number of patients are in a long-term state of depression. A prominent feature of MHD patients is chronic persistent inflammation, which is also an important mechanism for the onset of depression. Therefore, finding economically convenient inflammatory markers to predict and diagnose the onset of depression in MHD patients is of great value. As a novel inflammatory marker, systemic immune inflammation index (SII) can more comprehensively reflect the inflammation and immunity level of patients. This study aims to explore the relationship between SII and depressive symptoms in MHD patients., Methods: A cross-sectional study was conducted on 206 MHD patients from three dialysis centers. Based on the Hospital Anxiety and Depression Scale (HADS) scores, patients were divided into non-depression and depression groups. Inter group comparison and multivariate logistic regression analysis were performed to determine whether SII is an independent risk factor for depression in MHD patients. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of SII on depression symptoms in MHD patients., Results: According to the HADS scale score, 38.83% of the included patients were in a state of depression. After adjusting for all confounding factors, MHD patients with SII>963.93 had a 4.709 times higher risk of depression than those with SII ≤ 478.32 (OR=4.709, 95% CI 1.821-12.178, P<0.01). ROC analysis showed that SII>685.11 was the best cutoff value for MHD depression patients, and the area under the curve (AUC) was 0.681., Conclusions: High SII is an independent risk factor for depressed MHD patients and an ideal inflammatory marker for predicting and identifying depression in MHD patients as assessed by the HADS scale., 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 Han, Zhang, Kong, Liu, Zhang and Ren.)

Based on phylogenetic analysis, Candolleomyces (Psathyrellaceae, Agaricales) was established with Psathyrella candolleana as the type species. The basidiomes range from small to large and are typically terrestrial, lignicolous, and rarely fimicolous. We analysed the Candolleomyces species collected during five years in China, and based on morphological and molecular data (nrITS, nrLSU, and tef-1α ), we propose seven new Candolleomyces species viz. C. brevisporus , C. gyirongicus , C. lignicola , C. luridus , C. shennongdingicus , C. shennongjianus , and C. sichuanicus . Full descriptions, colour photographs, illustrations, phylogenetic analyses results, and comparisons with related Candolleomyces species of the new taxa are provided. This study enriches the species diversity of Candolleomyces in China.

Objective: To assess the capability of seven reference medical laboratories to detect BCR::ABL1 p210 transcription levels and to compare the results among those laboratories. Methods: The interlaboratory comparison was carried out in two stages. The samples were prepared by the reference laboratory. The quantitative values of BCR::ABL1 p210 of the comparison samples covered 0.001%-0.01%, 0.01%-0.1%, 0.1%-1%, 1%-10% and>10% in each stage. Real-time quantitative PCR (RT-PCR) and dPCR (digital PCR) were used to examine the samples. The conversion factor (CF) was calculated and validated for each laboratory. Results: In the RT-PCR comparison, one laboratory was failed to detect BCR::ABL1 p210 in fourteen samples at the first stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.133-0.338) and 95% limits of agreement within ±5 folds (upper limit 0.147-0.785, lower limit -0.770--0.109), and the corresponding CF values were calculated and validated. In the dPCR comparison, one laboratory did not report results at the second stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.026-0.267) and 95% limits of agreement within±5 folds (upper limit 0.084-0.991, lower limit -0.669--0.135), and the corresponding CF values were calculated and validated. The samples with BCR::ABL1 p210 quantitative values of 0.01%-0.1%, 0.1%-1%, 1%-10% and >10% could be detected by both RT-PCR and qPCR. When the quantitative value of BCR::ABL1 p210 was 0.001%-0.01%, the detection rate of dPCR was higher than that of RT-PCR (85.56% vs. 68.00%). Conclusions: A good consistency is present among various laboratories. The quantitative value of BCR::ABL1 p210 is comparable among laboratories as shown by the CF value conversion. For quantitative detection of BCR::ABL1 p210 deep molecular reaction, dPCR has a higher positive detection rate and more advantages than RT-PCR. To ensure the accuracy and reproducibility of the BCR::ABL1 p210 test, it is imperative for every laboratory to enhance their daily quality control practices.

Background: Periodontitis is a common oral disease and the chronic inflammation caused by it may influence the development of cancers in the upper gastrointestinal tract. Many observational studies have established a relationship between the two, but the results are not entirely consistent., Methods: Two-sample MR was performed using publicly available genome-wide association studies data for periodontitis, oral, gastric and oesophagal cancers. The Inverse Variance Weighting (IVW) method serves as the primary method, with MR Egger, Weighted Median, Simple Model and Weighted Model Algorithm methods as complementary methods to assess genetic causal associations. Cochran Q-test, MR-Egger regression and MR polytropic residuals and outliers were used to assess heterogeneity and horizontal pleiotropy., Results: IVW results did not support a causal association between periodontitis and oral (OR = 1.00, 95% CI: 1.00, 1.00) and oesophagal cancer (OR = 1.00, 95% CI: 1.00, 1.00). Similarly, there was again no causal association between periodontitis and gastric cancer, which was integrated with an OR of 1.04 (95% CI: 0.97, 1.12). Complementary method results were consistent with IVW and heterogeneity and horizontal pleiotropy were not found in most studies., Conclusions: The findings of our MR study do not support a causal relationship between periodontitis and oral, gastric and oesophagal cancers., (© 2024 Australian Dental Association.)

Insect protein extract is one of the high-quality protein sources and is frequently viewed as a potential nutrition alternative. However, a more precise method for protein measurement is still needed due to protein overestimation by the Kjeldahl method due to the presence of a large amount of chitin in insects. Therefore, we demonstrated the monitoring of chitin and protein extracted from yellow mealworm larvae through the information on molecular vibration obtained using Raman spectroscopy and infrared (IR) spectroscopy. The NH vibration at 3475 cm -1 is the characteristic peak of chitin in defatted product observed in the Raman spectra. The nitrogen-to-protein conversion factor in protein extracted from larvae by the Raman method was determined based on the NH vibration and found to be 5.66 ± 0.01. We also compared these experimental data to theoretical Raman and IR spectra and determined the possible reasons for why nitrogen elements in chitin affect the determination of protein content. The method of sequentially removing fat and protein could provide more accurate quantification of protein and chitin. Raman spectroscopy is feasible for various types of insects with high chitin content. Compared with the Kjeldahl method, the Raman method is a faster and more accurate measurement method. Moreover, it provides the content of impurities, purity, and structural information., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Obesity can affect periodontal tissues and exacerbate periodontitis. Pyroptosis, a newly identified type of inflammatory cell death, is involved in the development of periodontal inflammation. The saturated fatty acid palmitic acid (PA) is elevated in obese patients. The effect of PA on pyroptosis in periodontal ligament cells (PDLCs) and its underlying mechanisms remain unknown., Materials and Methods: Human PDLCs were isolated from healthy individuals and cultured for experiments. The effects of PA on PDLC pyroptosis and the underlying mechanisms were examined by transmission electron microscopy, quantitative real-time PCR and western blotting., Results: The morphology of PDLCs in the PA group indicated pyroptotic characteristics, including swollen cells, plasma membrane rupture and changes in subcellular organelles. PA induced inflammatory responses in PDLCs, as indicated by an increase in IL-1β in the cell culture supernatant. Furthermore, we found that the pyroptosis-related proteins caspase-1, caspase-4 and GSDMD were involved in PA-induced cell death. GSDMD and caspase-4 inhibitors alleviated pyroptotic death of PDLCs. Moreover, PA promoted NF-κB P65 phosphorylation. A NF-κB inhibitor decreased IL-1β expression and partly rescued cell death induced by PA., Conclusion: PA activated the NF-κB pathway and induced the inflammatory response in PDLCs. Caspase-4/GSDMD mediated PDLC pyroptosis induced by PA., (© 2023 Wiley Periodicals LLC.)

Ferroptosis and apoptosis are two types of regulated cell death that are closely associated with the pathophysiological processes of many diseases. The significance of ferroptosis-apoptosis crosstalk in cell fate determination has been reported, but the underlying molecular mechanisms are poorly understood. Herein mitochondria-mediated molecular crosstalk is explored. Based on a comprehensive spectroscopic investigation and mass spectrometry, cytochrome c-involved Fenton-like reactions and lipid peroxidation are revealed. More importantly, cytochrome c is found to induce ROS-independent and cardiolipin-specific lipid peroxidation depending on its redox state. In situ Raman spectroscopy unveiled that erastin can interrupt membrane permeability, specifically through cardiolipin, facilitating cytochrome c release from the mitochondria. Details of the erastin-cardiolipin interaction are determined using molecular dynamics simulations. This study provides novel insights into how molecular crosstalk occurs around mitochondrial membranes to trigger ferroptosis and apoptosis, with significant implications for the rational design of mitochondria-targeted cell death reducers in cancer therapy.

The selective interaction of cytochrome c (Cyt c ) with cardiolipin (CL) is involved in mitochondrial membrane permeabilization, an essential step for the release of apoptosis activators. The structural basis and modulatory mechanism are, however, poorly understood. Here, we report that Cyt c can induce CL peroxidation independent of reactive oxygen species, which is controlled by its redox states. The structural basis of the Cyt c -CL binding was unveiled by comprehensive spectroscopic investigation and mass spectrometry. The Cyt c -induced permeabilization and its effect on membrane collapse, pore formation, and budding are observed by confocal microscopy. Moreover, cytochrome c oxidase dysfunction is found to be associated with the initiation of Cyt c redox-controlled membrane permeabilization. These results verify the significance of a redox-dependent modulation mechanism at the early stage of apoptosis, which can be exploited for the design of cytochrome c oxidase-targeted apoptotic inducers in cancer therapy.

In situ analysis of membrane protein-ligand interactions under physiological conditions is of significance for both fundamental and applied science, but it is still a big challenge due to the limits in sensitivity and selectivity. Here, we demonstrate the potential of surface-enhanced resonance Raman spectroscopy (SERRS) for the investigation of membrane protein-protein interactions. Lipid biolayers are successfully coated on silver nanoparticles through electrostatic interactions, and a highly sensitive and biomimetic membrane platform is obtained in vitro. Self-assembly and immobilization of the reduced cytochrome b 5 on the coated membrane are achieved and protein native biological functions are preserved. Owing to resonance effect, the Raman fingerprint of the immobilized cytochrome b 5 redox center is selectively enhanced, allowing for in situ and real-time monitoring of the electron transfer process between cytochrome b 5 and their partners, cytochrome c and myoglobin. This study provides a sensitive analytical approach for membrane proteins and paves the way for in situ exploration of their structural basis and functions.

Sensitive and multiple detection of the biomarkers of type 1 diabetes mellitus (T1DM) is vital to the early diagnosis and clinical treatment of T1DM. Herein, we developed a SERS-based biosensor using polyvinylidene fluoride (PVDF) membranes as a flexible support for the detection of glutamic acid decarboxylase antibodies (GADA) and insulin autoantibodies (IAA). Two kinds of silver-gold core-shell nanotags embedded with Raman probes and attached with GADA or IAA antibodies were synthesized to capture the targets, enabling highly sensitive and highly selective detection of GADA and IAA. The embedded Raman probes sandwiched between silver and gold layers guaranteed spectral stability and reliability. Moreover, the utilization of two Raman probes enables simultaneous and multiplexing detection of both GADA and IAA, improving the detection accuracy for T1DM. The proposed SERS-based method has been proven feasible for clinical sample detection, demonstrating its great potential in sensitive, reliable, and rapid diagnosis of T1DM.

The crosstalk between mitochondria and endoplasmic reticula plays a crucial role in apoptotic pathways in which reactive oxygen species (ROS) produced by microsomal monooxygenase (MMO) are believed to accelerate cytochrome c release. Herein, we successfully demonstrate the potential of surface-enhanced resonance Raman spectroscopy (SERRS) for monitoring MMO-derived ROS formation and ROS-mediated cytochrome c release. Silver nanoparticles coated with nickel shells are used as both Raman signal enhancers and electron donors for cytochrome c. SERRS of cytochrome c is found to be sensitive to ROS, allowing for in situ probing of ROS formation with a cell death inducer. Label-free evaluation of ROS-induced apoptosis is achieved by SERRS-based monitoring of cytochrome c release in living cells. This study verifies the capability of SERRS for label-free, in situ, and real-time monitoring of the mitochondria-endoplasmic reticulum crosstalk in apoptosis and provides a novel strategy for the rational design and screening of ROS-inducing drugs for cancer treatment.

Oral submucous fibrosis (OSF) is a potentially malignant disorder of the oral mucosa; however, whether and how the fibrotic matrix of OSF is involved in the malignant transformation of epithelial cells remains unknown. Herein, oral mucosa tissue from patients with OSF, OSF rat models, and their controls were used to observe the extracellular matrix changes and epithelial-mesenchymal transformation (EMT) in fibrotic lesions. Compared with controls, oral mucous tissues from patients with OSF showed an increased number of myofibroblasts, a decreased number of blood vessels, and increased type I and type III collagen levels. In addition, the oral mucous tissues from humans and OSF rats showed increased stiffness, accompanied by increased EMT activities of epithelial cells. The EMT activities of stiff construct-cultured epithelial cells were increased significantly by exogenous piezo-type mechanosensitive ion channel component 1 (Piezo1) activation, and decreased by yes-associated protein (YAP) inhibition. During ex vivo implantation, oral mucosal epithelial cells of the stiff group showed increased EMT activities and increased levels of Piezo1 and YAP compared with those in the sham and soft groups. These results indicate that increased stiffness of the fibrotic matrix in OSF led to increased proliferation and EMT of mucosal epithelial cells, in which the Piezo1-YAP signal transduction is important., (Copyright © 2023 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Osteoarthritis is a degenerative disease characterized by abnormal neurovascularization at the osteochondral junctions, the regulatory mechanisms of which remain poorly understood. In the present study, a murine osteoarthritic model with augmented neurovascularization at the osteochondral junction is used to examine this under-evaluated facet of degenerative joint dysfunction. Increased extracellular RNA (exRNA) content is identified in neurovascularized osteoarthritic joints. It is found that the amount of exRNA is positively correlated with the extent of neurovascularization and the expression of vascular endothelial growth factor (VEGF). In vitro binding assay and molecular docking demonstrate that synthetic RNAs bind to VEGF via electrostatic interactions. The RNA-VEGF complex promotes the migration and function of endothelial progenitor cells and trigeminal ganglion cells. The use of VEGF and VEGFR2 inhibitors significantly inhibits the amplification of the RNA-VEGF complex. Disruption of the RNA-VEGF complex by RNase and polyethyleneimine reduces its in vitro activities, as well as prevents excessive neurovascularization and osteochondral deterioration in vivo. The results of the present study suggest that exRNAs may be potential targets for regulating nerve and blood vessel ingrowth under physiological and pathological joint conditions., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

This article concerns with the asynchronous boundary control for a class of Markov jump reaction-diffusion neural networks (MJRDNNs). In consideration of nonsynchronous behavior between the system modes and controller modes, a novel asynchronous boundary control design is proposed for MJRDNNs. Based on the designed asynchronous boundary controller, a sufficient criterion is established to ensure the stochastic finite-time boundedness for the considered MJRDNNs by constructing a Lyapunov-Krasovskii functional and utilizing Wirtinger-type inequality. Then, a sufficient condition is acquired to guarantee that MJRDNNs are stochastic finite-time bounded with H ∞ performance. Finally, a numerical example is provided to illustrate the effectiveness of the proposed design method.

We wished to summarize the clinical features of common variable immunodeficiency (CVID) complicated by non-cirrhotic portal hypertension (NCPH) and to deepen our understanding of it. The case data of CVID complicated with NCPH admitted to Peking Union Medical College Hospital from January 1983 to May 2021 were analyzed retrospectively to summarize their clinical characteristics. Six patients with CVID combined with NCPH (three of each sex; 16-45 years) were assessed. Four patients had portal hypertension. All patients had anemia, splenomegaly, a normal serum level of albumin and transaminases, and possibly increased levels of alkaline phosphatase and gamma-glutamyl transpeptidase. Two patients were diagnosed with esophagogastric fundic varices by gastroscopy. Two patients underwent splenectomy (which improved hematologic abnormalities partially). Four patients had autoimmune disease. Two cases were diagnosed with nodular regenerative hyperplasia (NRH) upon liver biopsy. Six patients were administered intravenous immunoglobulin-G (0.4-0.6 g/kg bodyweight) once every 3-4 weeks as basic therapy. Often, CVID complicated with NCPH has: (1) The manifestations of portal hypertension as the primary symptom. (2) Autoimmune-related manifestations. Imaging can provide important diagnostic clues. The etiology may be related to hepatic NRH and splenomegaly due to recurrent infections.

Introduction: Acute lung injury (ALI) is a common and devastating respiratory disease associated with uncontrolled inflammatory response and transepithelial neutrophil migration. In recent years, a growing number of studies have found that Ardisiae Japonicae Herba (AJH) has a favorable anti-inflammatory effect. However, its serum material basis and molecular mechanism are still unknown in ALI treatment. In this study, metabolomics and network analysis of serum pharmacochemistry were used to explore the therapeutic effect and molecular mechanism of AJH against lipopolysaccharide (LPS)-induced ALI. Methods: A total of 12 rats for serum pharmacochemistry analysis were randomly divided into the LPS group and LPS + AJH-treated group (treated with AJH extract 20 g/kg/d), which were administered LPS (2 mg/kg) by intratracheal instillation and then continuously administered for 7 days. Moreover, 36 rats for metabolomic research were divided into control, LPS, LPS + AJH-treated (5, 10, and 20 g/kg/d), and LPS + dexamethasone (Dex) (2.3 × 10 -4  g/kg/d) groups. After 1 h of the seventh administration, the LPS, LPS + AJH-treated, and LPS + Dex groups were administered LPS by intratracheal instillation to induce ALI. The serum pharmacochemistry profiling was performed by UPLC-Orbitrap Fusion MS to identify serum components, which further explore the molecular mechanism of AJH against ALI by network analysis. Meanwhile, metabolomics was used to select the potential biomarkers and related metabolic pathways and to analyze the therapeutic mechanism of AJH against ALI. Results: The results showed that 71 serum components and 18 related metabolites were identified in ALI rat serum. We found that 81 overlapping targets were frequently involved in AGE-RAGE, PI3K-AKT, and JAK-STAT signaling pathways in network analysis. The LPS + AJH-treated groups exerted protective effects against ALI by reducing the infiltration of inflammatory cells and achieved anti-inflammatory efficacy by significantly regulating the interleukin (IL)-6 and IL-10 levels. Metabolomics analysis shows that the therapeutic effect of AJH on ALI involves 43 potential biomarkers and 14 metabolic pathways, especially phenylalanine, tyrosine, and tryptophan biosynthesis and linoleic acid metabolism pathways, to be influenced, which implied the potential mechanism of AJH in ALI treatment. Discussion: Our study initially elucidated the material basis and effective mechanism of AJH against ALI, which provided a solid basis for AJH application., 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 © 2023 Han, Tian, Liu, Zhao, Liu, Hu, Feng and Li.)

In multienzymes cascade reaction, the inter-enzyme spacing is supposed to be a factor affecting the cascade activity. Here, a simple and efficient Y-shaped DNA scaffold is assembled using two partially complementary DNA single strands on magnetic microspheres, which is used to coimmobilize glucose oxidase (GOD) and horseradish peroxidase (HRP). As a result, on poly(vinyl acetate) magnetic microspheres (PVAC), GOD/HRP-DNA@PVAC multienzyme system is obtained, which can locate GOD and HRP accurately and control the inter-enzyme distance precisely. The distance between GOD and HRP is regulated by changing the length of DNA strand. It showed that the cascade activity is significantly distance-dependent. Moreover, the inter-enzyme spacing is not the closer the better, and too short distance would generate steric hindrance between enzymes. The cascade activity reached the maximum value of 967 U mg -1 at 13.6 nm, which is 3.5 times higher than that of free enzymes. This is ascribed to the formation of substrate channeling., (© 2023 Wiley-VCH GmbH.)

Objective: To explore the relevant factors of work-related musculoskeletal disorders (WMSDs) among dentists through Meta analysis, providing a basis for the prevention and control of WMSDs among dentists. Methods: In April 2022, cross-sectional research literatures on the prevalence correlation of WMSDs among Chinese dentists were searched in databases such as China National Knowledge Infrastructure, Wanfang, VIP, PubMed, Web of Science, and Em Base database. The search was conducted from the establishment of the database until April 2022, literatures were selected using keywords such as musculoskeletal disorders and dentists. To extract gender, age, length of service, disease classification and other related influencing factors as indicator, and prevalence was selected as the outcome indicator. After evaluating the quality of the literatures, RevMan 5.3 software was used to calculate the combined RD (95% CI ) values of the included literatures. Results: A total of 15 articles were included, with a total sample size of 3646 people. Meta analysis results showed that the prevalence of WMSDs among dentists in China was 80%, and the top three parts of the incidence rates were 65% of the waist, 58% of the neck, and 50% of the back. Gender, age, length of service, region and disease classification all increased the risk of WMSDs, and the combined effect size were 75%, 78%, 71%, 77% and 82% respectively ( P <0.05) . Conclusion: The occurrence of WMSDs among dentists in China is related to multiple factors such as gender, age, length of service and disease classification. The above risk factors should be taken into account in the workplace and preventive measures should be actively implemented to prolong the working life of dentists.

Background: Urinary bladder cancer (UBC) is a common malignancy of the urinary tract; however, the mechanism underlying its high recurrence and responses to immunotherapy remains unclear, making clinical outcome predictions difficult. Epigenetic alterations, especially DNA methylation, play important roles in bladder cancer development and are increasingly being investigated as biomarkers for diagnostic or prognostic predictions. However, little is known about hydroxymethylation since previous studies based on bisulfite-sequencing approaches could not differentiate between 5mC and 5hmC signals, resulting in entangled methylation results., Methods: Tissue samples of bladder cancer patients who underwent laparoscopic radical cystectomy (LRC), partial cystectomy (PC), or transurethral resection of bladder tumor (TURBT) were collected. We utilized a multi-omics approach to analyze both primary and recurrent bladder cancer samples. By integrating various techniques including RNA sequencing, oxidative reduced-representation bisulfite sequencing (oxRRBS), reduced-representation bisulfite sequencing (RRBS), and whole exome sequencing, a comprehensive analysis of the genome, transcriptome, methylome, and hydroxymethylome landscape of these cancers was possible., Results: By whole exome sequencing, we identified driver mutations involved in the development of UBC, including those in FGFR3, KDMTA, and KDMT2C. However, few of these driver mutations were associated with the down-regulation of programmed death-ligand 1 (PD-L1) or recurrence in UBC. By integrating RRBS and oxRRBS data, we identified fatty acid oxidation-related genes significantly enriched in 5hmC-associated transcription alterations in recurrent bladder cancers. We also observed a series of 5mC hypo differentially methylated regions (DMRs) in the gene body of NFATC1, which is highly involved in T-cell immune responses in bladder cancer samples with high expression of PD-L1. Since 5mC and 5hmC alternations are globally anti-correlated, RRBS-seq-based markers that combine the 5mC and 5hmC signals, attenuate cancer-related signals, and therefore, are not optimal as clinical biomarkers., Conclusions: By multi-omics profiling of UBC samples, we showed that epigenetic alternations are more involved compared to genetic mutations in the PD-L1 regulation and recurrence of UBC. As proof of principle, we demonstrated that the combined measurement of 5mC and 5hmC levels by the bisulfite-based method compromises the prediction accuracy of epigenetic biomarkers., (© 2023. The Author(s).)

The evidential reasoning (ER) rule has been widely applied in the multiple attribute decision making (MADM), which makes the decision-making process transparent and credible by using a belief structure. To improve the ability of the ER rule in dealing with the interval uncertainty, a new interval ER (IER) rule is proposed in this article. The interval uncertainty is described as the interval grade in the new frame of discernment (FoD) to model the local ignorance. It is proved that the IER rule is a generalization of the ER rule. To study the influence of perturbation on the IER rule, the perturbation is first introduced to the belief structure, and the perturbation analysis (PA) is conducted for the IER rule. An optimization model is established to estimate the perturbation threshold, which can measure the effectiveness of the inference result under perturbation. Two numerical examples and a case study are carried out, respectively, to show the implementation process of the proposed IER rule and validate its effectiveness in different decision-making scenarios.

Objective: To detect the body surface temperature of the relevant back- shu points in patients with chronic persistent asthma by infrared thermal imaging technology, and observe the specific changes of the body surface temperature of the relevant back- shu points under the condition of lung disease., Methods: Forty-five patients with chronic persistent asthma (observation group) and 45 healthy subjects (control group) were selected. The body surface temperature of bilateral Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) were measured by BK-MT02A medical infrared thermography., Results: The body surface temperature of bilateral Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) in the observation group was higher than that in the control group ( P <0.01, P <0.05). The body surface temperature of bilateral Feishu (BL 13) and Geshu (BL 17) was higher than that of ipsilateral Pishu (BL 20) and Shenshu (BL 23) in the two groups ( P <0.01, P <0.05). There was no statistically significant difference in body surface temperature between ipsilateral Feishu (BL 13) and Geshu (BL 17), between ipsilateral Pishu (BL 20) and Shenshu (BL 23) ( P >0.05)., Conclusion: The pathological increase of body surface temperature of Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) in patients with chronic persistent asthma indicates that above acupoints have specificity in reflecting lung diseases. The Feishu (BL 13) and Geshu (BL 17), which have significantly increased body surface temperature, not only provide objective basis for the pathological pathogenesis of "deficiency in origin and excess in symptom" in patients with chronic persistent asthma, but also reflect the different expressions of different acupoints on the same meridian for the lung diseases.

Obstructive sleep apnea (OSA) is a sleep-related breathing disorder characterized by intermittent and recurrent upper airway collapse during sleep that leads to chronic intermittent hypoxia (CIH). The genioglossus (GG) is the largest dilator muscle, which controls the upper airway and plays an important role in OSA pathology. Elucidating its genetic alterations may help identify potential targets for OSA. However, the genetic aspects of the GG in CIH mice remain unclear. Here, we have conducted an RNA sequencing (RNA-Seq) analysis to assess the differentially expressed genes (DEGs) in the GG between CIH mice and normoxia (NOR) mice. A total of 637 DEGs were identified to be dysregulated in CIH mice compared with control mice. Bioinformatics analysis showed that the DEGs were related to various physiological processes, such as the endogenous stimulus responses, cellular component organization and metabolic processes. Extracellular matrix (ECM)-receptor interaction was the top KEGG pathway in the environmental information processing category with high significance and large fold changes. From the gene weight distributions of collagen (Col)-related biological processes (BPs), we found several significant DEGs, such as Col1a1, Col1a2, Mmp2, Col3a1, Col5a1, Fmod, and Col5a2. A PPI network showed that Col1a1 was linked to ECM-receptor interactions, responses to reactive oxygen species (ROS) and Col-related BPs. It was verified in vivo and in vitro that hypoxia can induce excess ROS and reduce Col expression levels. Moreover, we found NAC can effectively scavenge ROS and restore collagen synthesis. These findings contribute to a better understanding of the mechanisms linking OSA and upper airway muscle injury and may help identify potential therapeutic targets., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Oral submucous fibrosis (OSF) is a chronic, inflammatory and potentially malignant oral disorder. Its pathophysiology is extremely complex, including excessive collagen deposition, massive inflammatory infiltration, and capillary atrophy. However, the existing clinical treatment methods do not fully take into account all the pathophysiological processes of OSF, so they are generally low effective and have many side effects. In the present study, we developed an injectable sodium hyaluronate/45S5 bioglass composite hydrogel (BG/HA), which significantly relieved mucosal pallor and restricted mouth opening in OSF rats without any obvious side effects. The core mechanism of BG/HA in the treatment of OSF is the release of biologically active silicate ions, which inhibit collagen deposition and inflammation, and promote angiogenesis and epithelial regeneration. Most interestingly, silicate ions can overall regulate the physiological environment of OSF by down-regulating α-smooth muscle actin (α-SMA) and CD68 and up-regulating CD31 expression, as well as regulating the expression of pro-fibrotic factors [transforming growth factor-β1 (TGF-β1), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and tissue inhibitors of metalloproteinase-1 (TIMP-1)] and anti-fibrotic factors [interleukin-1β (IL-1β)] in macrophage. In conclusion, our study shows that BG/HA has great potential in the clinical treatment of OSF, which provides an important theoretical basis for the subsequent development of new anti-fibrotic clinical preparations. STATEMENT OF SIGNIFICANCE: : Oral submucous fibrosis (OSF) is a chronic, inflammatory and potentially malignant mucosal disease with significant impact on the quality of patients' life. However, the existing clinical treatments have limited efficacy and many side effects. There is an urgent need for development of specific drugs for OSF treatment. In the present study, bioglass (BG) composited with sodium hyaluronate solution (HA) was used to treat OSF in an arecoline-induced rat model. BG/HA can significantly inhibit collagen deposition, regulate inflammatory response, promote angiogenesis and repair damaged mucosal epithelial cells, and thereby mitigate the development of fibrosis in vivo., 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 © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objectives: Investigate the biomechanical characteristics in tracheostomized patients with aspiration following acquired brain injury (ABI) and further explore the relationship between the biomechanical characteristics and aspiration. Methods: This is a single-center cross-sectional study. The tracheostomized patients with aspiration following ABI and age-matched healthy controls were recruited. The biomechanical characteristics, including velopharynx (VP) maximal pressure, tongue base (TB) maximal pressure, upper esophageal sphincter (UES) residual pressure, UES relaxation duration, and subglottic pressure, were examined by high-resolution manometry and computational fluid dynamics simulation analysis. The penetration−aspiration scale (PAS) score was evaluated by a videofluoroscopic swallowing study. Results: Fifteen healthy subjects and fifteen tracheostomized patients with aspiration following ABI were included. The decreased VP maximal pressure, increased UES residual pressure, and shortened UES relaxation duration were found in the patient group compared with the control group (p < 0.05). Furthermore, the subglottic pressure significantly decreased in patients (p < 0.05), while no significant difference was found in TB maximal pressure between groups (p > 0.05). In addition, in the patient group, VP maximal pressure (rs = −0.439; p = 0.015), UES relaxation duration (rs = −0.532; p = 0.002), and the subglottic pressure (rs = −0.775; p < 0.001) were negatively correlated with the PAS score, while UES residual pressure (rs = 0.807; p < 0.001) was positively correlated with the PAS score (p < 0.05), the correlation between TB maximal pressure and PAS score (rs = −0.315; p = 0.090) did not reach statistical significance. Conclusions: The biomechanical characteristics in tracheostomized patients with aspiration following ABI might manifest as decreased VP maximal pressure and subglottic pressure, increased UES residual pressure, and shortened UES relaxation duration, in which VP maximal pressure, UES relaxation duration, subglottic pressure, and UES residual pressure were correlated with aspiration.

Ovarian cancer (OC), particularly high-grade serous cancer (HGSC), is the leading cause of mortality among gynecological cancers owing to the treatment difficulty and high recurrence probability. As therapeutic drugs approved for OC, poly ADP-ribose polymerase inhibitors (PARPi) lead to synthetic lethality by inhibiting single-strand DNA repair, particularly in homologous recombination-deficient cancers. However, even PARPi have distinct efficacies and are prone to have drug resistance, the molecular mechanisms underlying the PARPi resistance in OC remain unclear. A patient-derived organoid platform was generated and treated with a PARPi to understand the factors associated with PARPi resistance. PARPi significantly inhibits organoid growth. After 72 h of treatment, both the size of organoids and the numbers of adherent cells decreased. Moreover, immunofluorescence results showed that the proportion of Ki67 positive cells significantly reduced. When the PARPi concentration reached 200 nM, the percentage of Ki67 + /4',6-diamidino-2-phenylindole (DAPI) cells decreased approximately 50%. PARPi treatment also affected the expression of genes involved in base excision repair and cell cycle. Functional assays revealed that PARPi inhibits cell growth by upregulating early apoptosis. The expression levels of several key genes were validated. In addition to previously reported genes, some promising genes FEN1 and POLA2 , were also be founded. The results demonstrate the complex effects of PARPi treatment on changes in potential genes relevant to PARPi resistance, and provide perspectives for further research on the PARPi resistance mechanisms.

Objective: To analyze the characteristics of full-field stimulus thresholds (FST) in patients with middle-and late-stage inherited retinal dystrophy (IRD), and to explore the feasibility of the FST test in evaluating the retinal function for IRD patients. Methods: It was a retrospective case series study. Twenty-eight patients with IRD whose full-field electroretinogram (ERG) results showed no electrical activity (20 patients) or a serious decrease in electrical activity (8 patients) were enrolled, including 17 males and 11 females, with a median age of 32 years. Ten normal controls were also enrolled. All eyes had a measurement of best corrected visual acuity (BCVA) and an ERG test. FST stimulated by red, blue and white lights were examined with an electrophysiological instrument. The decimal value of BCVA was converted to logarithm of the minimum angle of resolution. Data of the better eye of each participant were used for statistical analysis. Independent sample t -test was used to analyze the difference in FST among patients. Linear regression was used to analyze the correlation between FST, visual acuity and ERG amplitudes. Results: The BCVA of all eyes was 0.7±0.6. Under the stimulation of red, blue and white lights, the FST were(-27.0±7.1), (-47.4±12.2) and(-41.7±11.5) dB in the 8 eyes with decreased electrical activity, (-16.3±7.0), (-27.2±13.7) and(-23.5±12.5) dB in the 20 eyes with no electrical activity, and(-39.9±4.0), (-65.8±4.0) and(-58.5±3.4) dB in the 10 control eyes, respectively. The FST of IRD patients were higher than the normal controls. The FST with red, blue and white lasers in eyes with no electrical activity were higher than those with severely reduced electrical activity ( t =-3.472, -3.506, -3.433; all P =0.002). The BCVA was not correlated with the FST under the red, blue and white light stimulation in eyes with a serious reduction in electrical activity ( r =0.134, 0.011, 0.010; P =0.055, 0.601, 0.611). There was a linear correlation between the red light stimulus FST and the b-wave amplitude of flicker ERG response ( r =-0.591, P =0.026), but there was no significant correlation between other amplitudes and FST. Conclusions: The FST test is a supplementary method to evaluate the retinal function of patients with middle-and late-stage IRD. It can quantitatively reflect the function of rod and cone cell system. As the retinal function of IRD patients decreases, the FST gradually increase.

Precocious puberty in children is one of the common endocrine diseases in paediatrics. Epidemiological surveys have shown that the number of children with precocious puberty has significantly increased globally. Precocious puberty negatively affects the physical and mental health of children and may increase the risk of hypertension, diabetes, obesity and infertility in adulthood. Therefore, the initiating factors of adolescence have become core issues in the study of sexual development in children. Owing to developments in molecular genetics, many studies have been able to show that precocious puberty is mostly resulted in autosomal inheritance. For instance, makorin ring finger protein 3 gene (MKRN3) may be implicated in familial CPP. Gonadotropin-releasing hormone agonist (GnRHa) is the gold standard for treatment, but its safety still requires long-term evaluation and management. Traditional medicinal plants have been used in clinical treatments and in exploring novel treatment methods. From the collected datas, in Asia, traditional Chinese medicine treatment is based on the principles of nourishing Yin, lowering fire and draining fire from the liver to help precocious children and alleviate or delay the onset of precocious puberty by medicinal plants such as Anemarrhena asphodeloides Bge., Phellodendron amurense Rupr., Rehmannia glutinosa and Poria cocos Wolf. They play an important role in exploring the pharmacological mechanisms of precocious puberty treatment effects and drug development. Therefore, by elucidating the occurrence and development of precocious puberty, this review provides novel and valuable insights of paediatric endocrine therapy accessing the published researches on the effectiveness of traditional herbal medicine in the treatment of precocious puberty and its therapeutic mechanisms., Competing Interests: Conflict of Interest Statement The authors declare that there are no conflicts of interest., (Copyright © 2022. Published by Elsevier Masson SAS.)

Hyperoside (HP), as a natural product, can promote proliferation and differentiation of osteoblasts and presents a protective effect on ovariectomized (OVX) mice. However, the inhibitory effect of HP on osteoclasts (OCs) and the potential mechanism remain to be elucidated. In this study, it was found that HP could effectively inhibit the differentiation and bone resorption of OCs, and its intrinsic molecular mechanism was related to the inhibition of TRAF6/p38 MAPK signaling pathway. Therefore, HP could be a promising natural compound for lytic bone diseases.

The overexpression of specific biomarkers in serum is closely related to diseases, and accurate and sensitive detection of them is beneficial for the early diagnosis and treatment of cancer. In this study, we developed a novel surface-enhanced Raman spectroscopy (SERS)-based aptasensor to detect the prostate-specific antigen biomarkers, consisting of total prostate-specific antigen (PSA) and free prostate-specific antigen (f-PSA). A composite structure containing arrays of polystyrene colloidal sphere @Ag shell (PS@Ag) was fabricated as a SERS-active chip. A complementary DNA probe (SH-DNA) and PSA aptamer (Apt) were immobilised stepwise on the chip, followed by the binding of a Raman reporter methylene blue (MB) to the guanine base of the aptamer. PSA-Apt recognition causes the release of MB-Apt and a decrease in the SERS intensity of MB on the chip, which correlates with the PSA concentration. The proposed biosensor has high spectral reproducibility, selectivity, and sensitivity and successfully determines the PSA levels in serum samples collected from prostate cancer patients, demonstrating great potential for clinical diagnosis., 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 © 2022 Elsevier B.V. All rights reserved.)

Malignant glioma is a highly heterogeneous and invasive primary brain tumor characterized by high recurrence rates, resistance to combined therapy, and dismal prognosis. Glioma stem cells (GSCs) are likely responsible for tumor progression, resistance to therapy, recurrence, and poor prognosis owing to their high self-renewal and tumorigenic potential. As a family member of BMP signaling, bone morphogenetic protein4 (BMP4) has been reported to induce the differentiation of GSCs and neural stem cells (NSCs). However, the molecular mechanisms underlying the BMP4-mediated effects in these two cell types are unclear. In this study, we treated hGSCs and hNSCs with BMP4 and compared the phenotypic and transcriptional changes between these two cell types. Phenotypically, we found that the growth of hGSCs was greatly inhibited by BMP4, but the same treatment only increased the cell size of hNSCs. While the RNA sequencing results showed that BMP4 treatment evoked significantly transcriptional changes in both hGSCs and hNSCs, the profiles of differentially expressed genes were distinct between the two groups. A gene set that specifically targeted the proliferation and differentiation of hGSCs but not hNSCs was enriched and then validated in hGSC culture. Our results suggested that hGSCs and hNSCs responded differently to BMP4 stimulation. Understanding and investigating different responses between hGSCs and hNSCs will benefit finding partner factors working together with BMP4 to further suppress GSCs proliferation and stemness without disturbing NSCs., (© 2022. The Author(s).)

Acute-exacerbation chronic obstructive pulmonary disease (AECOPD) is mainly associated with acute respiratory tract infection. In recent years, a growing number of studies have found that Tanreqing capsule (TRQ) has a favorable anti-inflammatory effect. In this study, we used network pharmacology and pharmacodynamics to explore the molecular mechanism and effects of TRQ in AECOPD treatment. To further understand the molecular mechanism of TRQ in AECOPD treatment, we used the network pharmacology to predict components of TRQ, TRQ-related targets, AECOPD-related targets, and pathways. In addition, we used the cigarette-smoke/lipopolysaccharide -induced AECOPD experimental model in Sprague-Dawley rats (72 rats randomly divided into six groups [n = 12 each]: control, model, high-TRQ [TRQ-H], medium-TRQ [TRQ-M], low-TRQ, and dexamethasone [Dex]) to evaluate the therapeutic effects of TRQ and to verify the network pharmacology. We found that 59 overlapping targets based on component-and AECOPD-related targets were frequently involved in the advanced glycation end product-receptor for advanced glycation end product signaling pathway in diabetic complications, the phosphatidylinositol-3-kinase-protein kinase B signaling pathway, and the hypoxia-inducible factor 1 signaling pathway, which might play important roles in the anti-inflammatory mechanism of TRQ in AECOPD treatment. Moreover, TRQ groups exerted protective effects against AECOPD by reducing the infiltration of inflammatory cells. Meanwhile, TRQ-M and TRQ-H groups significantly downregulated or upregulated the expression of tumor necrosis factor, interleukin (IL) 6, C-reactive protein, IL10, and serum amyloid A, as key targets in network pharmacology, in the serum and bronchoalveolar lavage fluid to achieve anti-inflammatory efficacy. Our study showed that TRQ had better anti-inflammatory efficacy against AECOPD, and initially elucidated its molecular mechanism. Moreover, our study also provides a new strategy to explore effective mechanism of TRQ against AECOPD; and further studies are needed to validate the biological processes and pathways of TRQ against AECOPD., (© 2022. The Author(s).)

Additive manufacturing of fiber-reinforced polymers is one of the latest technical developments in composites manufacturing. However, there is a severe shortage of research into continuous fiber-reinforced polymers manufactured through stereolithography. For the first time, this article investigates the fracture properties of continuous carbon fiber-reinforced polymer produced by three-dimensional stereolithography printing. Compact tension (CT) specimens, both plain and fiber reinforced, were produced and tested systematically. The results showed a significant improvement in fracture toughness for fiber-reinforced specimens when compared with plain ones. The positioning of fiber bundles had a substantial effect on fracture properties, and a higher fracture toughness was reported for specimens with the fiber bundle placed closer to the crack tip. By increasing the number of fiber bundles, a significant increase in fracture toughness was reported when compared with the sample with a single fiber bundle, indicating a strong contribution of fiber volume. Also, the contribution appeared to be most effective when the fiber bundles were placed symmetrically in the thickness direction. The study is of importance and value for the development of the stereolithography technique in manufacturing continuous fiber-reinforced composites with enhanced mechanical properties., Competing Interests: No competing financial interests exist., (Copyright 2022, Mary Ann Liebert, Inc., publishers.)

Innovative application of surface-enhanced Raman scattering (SERS) for rapid and nondestructive analyses has been gaining increasing attention for food safety and quality. SERS is based on inelastic scattering enhancement from molecules located near nanostructured metallic surfaces and has many advantages, including ultrasensitive detection and simple protocols. Current SERS-based quality analysis contains composition and structural information that can be used to establish an electronic file of the food samples for subsequent reference and traceability. SERS is a promising technique for the detection of chemical, biological, and harmful metal contaminants, as well as for food poisoning, and allergen identification using label-free or label-based methods, based on metals and semiconductors as substrates. Recognition elements, including immunosensors, aptasensors, or molecularly imprinted polymers, can be linked to SERS tags to specifically identify targeted contaminants and perform authenticity analysis. Herein, we highlight recent studies on SERS-based quality and safety analysis for different foods categories spanning the whole food chain, 'from farm to table' and processing, genetically modified food, and novel foods. Moreover, SERS detection is a potential tool that ensures food safety in an easy, rapid, reliable, and nondestructive manner during the COVID-19 pandemic.

Malignant Glioma is characterized by strong self-renewal potential and immature differentiation potential. The main reason is that malignant glioma holds key cluster cells, glioma stem cells (GSCs). GSCs contribute to tumorigenesis, tumor progression, recurrence, and treatment resistance. Interferon-beta (IFN-β) is well known for its anti-proliferative efficacy in diverse cancers. IFN-β also displayed potent antitumor effects in malignant glioma. IFN-β affect both GSCs and Neural stem cells (NSCs) in the treatment of gliomas. However, the functional comparison, similar or different effects of IFN-β on GSCs and NSCs are rarely reported. Here, we studied the similarities and differences of the responses to IFN-β between human GSCs and normal NSCs. We found that IFN-β preferentially inhibited GSCs over NSCs. The cell body and nucleus size of GSCs increased after IFN-β treatment, and the genomic analysis revealed the enrichment of the upregulated immune response, cell adhesion genes and down regulated cell cycle, ribosome pathways. Several typical cyclin genes, including cyclin A2 (CCNA2), cyclin B1 (CCNB1), cyclin B2 (CCNB2), and cyclin D1 (CCND1), were significantly downregulated in GSCs after IFN-β stimulation. We also found that continuous IFN-β stimulation after passage further enhanced the inhibitory effect. Our study revealed how genetic diversity resulted in differential effects in response to IFN-β treatment. These results may contribute to improve the applications of IFN-β in anti-cancer immunotherapy. In addition, these results may also help to design more effective pharmacological strategies to target cancer stem cells while protecting normal neural stem cells., (© 2022. The Author(s).)

Emerging evidence greatly implicates that microRNA-450a (miR-450a) plays an essential role in cancer pathobiology. While the pathological role of miR-450a in breast carcinogenesis remains enigmatic. Herein, we showed that miR-450a was lowly expressed in breast cancer cell lines compared with normal, and low miR-450a expression was associated with poor survival in patients with breast cancer. We revealed that miR-450a mimic transfected breast cancer cells (T47D and BT474) exhibited attenuated capacities of proliferation, migration, and invasion in vitro, and miR-450a suppressed T47D cell growth in a xenograft tumor model. Mechanistically, cAMP response element-binding protein 1 (CREB1) was negatively targeted by miR-450a, and CREB1 deletion mimicked the effects of miR-450a mimic treatment. Bioinformatics analysis further revealed that elevated expression of CREB1 correlated with poor prognosis in patients with breast cancer and miR-450a level was negatively correlated with CREB1 level in breast cancer. Additionally, miR-450a inhibited the phosphorylation of phosphatidylinositol 3-kinase/V-akt murine thymoma viral oncogene homolog (PI3K/AKT) and the activities of matrix metalloproteinase-2/9 (MMP-2/9). The following rescue assay indicated that CREB1 was implicated in the anti-tumoral effect of mR-450a in breast carcinoma. All these observations disclosed that miR-450a negatively regulates the growth and metastatic property of breast carcinoma cells., (© 2022 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Generation of reactive oxygen species (ROS) are possibly induced by the crosstalk between mitochondria and endoplasmic reticula, which is physiologically important in apoptosis. Cytochrome c (Cyt c) is believed to play a crucial role in such signaling pathway by interrupting the coupling within microsomal monooxygenase (MMO). In this study, the correlation of ROS production with the electron transfer between Cyt c and the MMO system is investigated by resonance Raman (RR) spectroscopy. Binding of Cyt c to MMO is found to induce the production of ROS, which is quantitatively determined by the in-situ RR spectroscopy reflecting the interactions of Cyt c with generated ROS. The amount of ROS that is produced from isolated endoplasmic reticulum depends on the redox state of the Cyt c, indicating the important role of oxidized Cyt c in accelerating apoptosis. The role of electron transfer from MMO to Cyt c in the apoptotic mitochondria-endoplasmic reticulum pathway is accordingly proposed. This study is of significance for a deeper understanding of how Cyt c regulates apoptotic pathways through the endoplasmic reticulum, and thus may provide a rational basis for the design of antitumor drugs for cancer therapy., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Here, we demonstrate the first example of 3-isothiocyanato thiobutyrolactone serving as a useful building block in the Michael/cyclization reaction with alkylidene pyrazolones for the enantioselective construction of optically active structural bispiro[pyrazolone-thiobutyrolactone] skeletons containing three contiguous stereocenters with two spiroquaternary stereocenters. These products were smoothly afforded in up to 90% yield, >20 : 1 dr and >99% ee with chiral squaramide as the catalyst under mild conditions. Notably, this is also the first example of the merger of a spirocyclic pyrazolone scaffold with a spirocyclic thiobutyrolactone scaffold, potentially useful in medicinal chemistry.

The present study explored the correlation between the hydrodynamic size(i.e., hydrated particle size) and the surface component distribution of spray-dried powder based on the binary system model of berberine hydrochloride and dextran. A variety of mixture solutions containing substances of different proportions were prepared, and the hydrated particle sizes of the solutions were measured by laser light scattering technique. Then the effects of molecular weight and mixing proportion on the particle size were analyzed. After the solutions were spray-dried, the surface components of spray-dried powder were determined by X-ray photoelectron spectroscopy. The changes of hydrated particle size of the two substances in different solutions were measured with the altered solution environments, and the distribution of surface components after spray-drying was observed. The results of particle size measurement showed that different solution environments would change the hydrodynamic size of substances. Specifically, the particle size of berberine hydrochloride increased with the increase in ionic strength and solution pH, while the particle size of dextran decreased with the increase in ionic strength and increased with the increase in solution pH. The results of surface components of the spray-dried powder indicated that berberine hydrochloride was prone to accumulate on the surface of particles during spray-drying because of its large hydrodynamic size. Therefore, hydrodynamic size is considered an important factor affecting the surface component distribution of spray-dried powder. As revealed by scanning electron microscopy of the particle morphology of spray-dried powder, the particles of berberine hydrochloride spray-dried powder were irregularly elliptic, and the particles of dextran and mixture spray-dried powders were irregularly spherical with the shrunken surface. Finally, the FT4 powder rheometer and DVS instrument were used to determine the stability, adhesion, and hygroscopicity of the powder. The results showed that when berberine hydrochloride was enriched on the surface, the adhesion of the mixture increased and the fluidity became worse, but the hygroscopicity was improved to a certain extent. In addition, as found by hygroscopic kinetic curve fitting of spray-dried powder, the hygroscopic behaviors of all spray-dried powder conformed to the double exponential function.

Background: Established neuroendocrine signals do not sufficiently account for the exercise-induced increase in glucose production. Using an innovative, yet classical cross-circulation procedure, we studied whether contracting muscle produces a factor that directly stimulates hepatic glycogenolysis. Methods: Isolated rat hindquarters were perfused in series with isolated livers. Results: Stimulation of the sciatic nerve of one or both legs resulted in an increase in force, which rapidly waned. During one-legged contractions, hepatic glucose production increased initially (from −0.9 ± 0.5 (mean ± SE) to 3.3 ± 0.7 µmol/min, p < 0.05). The peak did not differ significantly from that seen after 20 nM of epinephrine (5.1 ± 1.2 µmol/min, p > 0.05). In response to two-legged contractions, the increase in hepatic glucose production (to 5.4 ± 1.3 µmol/min) was higher (p < 0.05) and lasted longer than that seen during one-legged contractions. During contractions, peak hepatic glucose output exceeded concomitant hepatic lactate uptake (p < 0.05), and glucose output decreased to basal levels, while lactate uptake rose to a plateau. Furthermore, in separate experiments an increase in lactate supply to isolated perfused livers increased lactate uptake, but not glucose output. In intact rats, intra-arterial injection of extract made from mixed leg muscle elicited a prolonged increase (p < 0.05) in plasma glucose concentration (from 5.2 ± 0.1 mM to 8.3 ± 1.5 mM). In perfused livers, muscle extract increased glucose output dose dependently. Fractionation by chromatography of the extract showed that the active substance had a MW below 2000. Conclusion: This study provides evidence that contracting skeletal muscle may produce a hormone with a MW below 2000, which enhances hepatic glycogenolysis according to energy needs. Further chemical characterization is warranted.

Ethnopharmacological Relevance: The Bu-Fei formula (BFF) has a positive effect on chronic obstructive pulmonary disease (COPD). However, its therapeutic mechanisms against COPD remain unknown., Aim of the Study: To explore BFF's therapeutic effect on COPD and pharmacological mechanisms., Materials and Methods: First, the effect of BFF on rats with COPD was studied. Rats were randomly assigned to the blank, COPD, BFF treatment, and aminophylline (APL) treatment groups. From weeks 1-8, the COPD model was established by Klebsiella pneumoniae (KP) and cigarette smoke. Then, rats were given corresponding treatment for 8 weeks. The lung function of the rats was analyzed by whole-body plethysmography and pulmonary function testing, lung histopathology by electron microscopy and hematoxylin and eosin staining, and protein levels by immunohistochemistry. Next, the key components and targets of BFF in COPD were screened by network pharmacology analysis. Finally, the possible mechanism was verified through molecular docking and in vivo experiments., Results: BFF significantly improved lung function and lung histopathology in COPD rats and inhibit inflammation and collagen deposition in lung tissues. Also, 46 bioactive compounds and 136 BFF targets related to COPD were identified; among them, 3 compounds (quercetin, luteolin, and nobiletin) and 6 core targets (Akt1, BCL2, NF-κB p65, VEGFA, MMP9, and Caspase 8) were the key molecules associated with the mechanisms of BFF. The target enrichment analysis suggested that BFF's mechanisms might involve the apoptosis-related pathway; this possibility was supported by the molecular docking data. Lastly, BFF was indicated to increase the expression of core target genes and the production of apoptosis-related proteins., Conclusions: BFF affects COPD by regulating the apoptosis-related pathways and targets., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)