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Synthetic biomaterials can be used as instructive biological milieus to guide cellular behaviour and function. To further realize this application, we synthesized a series of structurally similar hydrogels and tested their ability to modulate angiogenesis. Hydrogels were synthesized from poly(DTE-co-x% DT carbonate) crosslinked by y% poly(ethylene glycol) (PEG). Hydrogel desaminotyrosyl tyrosine (DT) contents (x%) ranged from 10-100%, and crosslink densities (y% PEG-crosslinker) ranged from 5-80%. The hydrogels were fashioned into porous scaffolds with highly interconnected macro- and micro-pore (>100 and

Carbendazim abuse in agriculture can lead to the residue in water and food, which may bring about adverse effects to human's health. In this study, we report the solvothermal synthesis of free-metal single TT-COF with one-step strategy and the TT-COF-based electrochemical sensor is fabricated for the further sensing of carbendazim. The TT-COF possesses high surface area, excellent conductivity and outstanding electrocatalytic activity. Therefore, the TT-COF/GCE is applied for the determination of carbendazim with CV and DPV techniques. This TT-COF/GCE sensor shows wide linear range of 0.005-5 μM and the low limit of detection (LOD) of 2.21 nM towards the detection of carbendazim. More importantly, the projected TT-COF/GCE sensor demonstrates satisfactory recoveries by estimating carbendazim in apple, tomato and pear juice real samples., 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 Ltd. All rights reserved.)

Covalent organic frameworks (COFs) can be rationally designed with functional organic ligands to improve the electrochemical responsiveness of the electrode toward certain medicinal compounds. In this study, we synthesized a COF-Ni electrocatalyst material, which is formed by covalent coupling of electron-rich 2,3,6,7-tetrakis (4-formylphenyl) tetrakis (4-imidazolyl) (TTF-4CHO) and hole-rich 5,10,15,20-tetrakis (4-aminophenyl) porphyrin nickel(II) (TAPP-Ni). The reasonable electron transfer path design, the large specific surface area of the COF and the physical properties of ordered nanopores, as well as the Ni-N 4 bond as a highly active catalytic center, allow the COF-Ni material modified electrode to exhibit excellent sensing performance for acetaminophen (ACOP). The detection limit for ACOP is as low as 47.6 nM, with a linear range of 1-1500 μM, which is better than for most of the reported sensors. With superior interference resistance and good stability performance, COF-Ni is a highly suited electrode modification material for real-world sample detection, which provided a new perspective for application of COF materials in drug analysis.

Background: Sepsis is a lethal disease due to uncontrolled inflammatory responses. Macrophages play an important role in sepsis-associated inflammation. Jing Si Herbal Tea (JSHT) is a plant-based regimen with anti-inflammatory properties designed to treat respiratory diseases; however, its underlying therapeutic mechanism remains unclear. This study aimed to investigate the effects of JSHT on macrophage polarization and inflammatory signaling in lipopolysaccharide (LPS)-induced inflammation to provide therapeutic approaches for inflammatory diseases. Methods: RAW264.7 cells were stimulated with LPS (1 µg/mL for 16 h) to induce inflammatory responses and treated by JSHT (0.0125% concentration for 4 h) in the experimental groups (Control, JSHT, LPS, Pre-JSHT, and Post-JSHT groups). We investigated the protein and cytokine expression levels using western blotting and enzyme-linked immunosorbent assay (ELISA). Macrophage morphology was observed using immunofluorescence staining. The polarization surface markers were detected by flow cytometry. Results: In the LPS group, the expressions of the inflammatory signaling (pERK, pJNK, and nuclear NFκB) and the pro-inflammatory cytokine levels (TNF-α, IL-1β, and IL-6) were significantly increased, with M1 polarization (CD68+/CD80+) compared to the Control group. In the Pre-JSHT and Post-JSHT groups, the expressions of the inflammatory signaling and the pro-inflammatory cytokine levels were significantly decreased, with a higher M2 polarization ratio (CD163+/CD206+) compared to the LPS group. RAW264.7 cells exhibited filopodia protruding from the cell surface in the LPS group, which were inhibited in the Pre-JSHT and Post-JSHT groups. Conclusions: LPS induced M1 polarization with elevated inflammatory signaling and cytokine levels, while JSHT not only decreased M1 polarization but also promoted M2 polarization with decreased inflammatory responses. We propose JSHT as a potential anti-inflammatory agent against LPS-induced inflammation., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

HLA-A*02:407 differs from HLA-A*02:01:01:01 by one nucleotide substitution in codon 109 in exon 3., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In this research, the TT-COF(Fe)@NH 2 -CNTs was innovatively prepared through a post-modification synthetic process functionalized TT-COF@NH 2 -CNTs with active site (Fe), where TT-COF@NH 2 -CNTs was prepared via a one-pot strategy using 5,10,15,20-tetrakis (para-aminophenyl) porphyrin (TTAP), 2,3,6,7-tetra (4-formylphenyl) tetrathiafulvalene (TTF) and aminated carbon nanotubes (NH 2 -CNTs) as raw materials. The complex TT-COF(Fe)@NH 2 -CNTs material possessed porous structures, outstanding conductivity and rich catalytic sites. Thus, it can be adopted to construct electrochemical sensor with glassy carbon electrode (GCE). The TT-COF(Fe)@NH 2 -CNTs/GCE can selectively detect luteolin (Lu) with a wide linear plot ranging from 0.005 to 3 μM and a low limit of detection (LOD) of 1.45 nM (S/N = 3). The Lu residues in carrot samples were determined using TT-COF(Fe)@NH 2 -CNTs sensor and UV-visible (UV-Vis) approach. This TT-COF(Fe)@NH 2 -CNTs/GCE sensor paves the way for the quantification of Lu through a cost-efficient and sensitive electrochemical approach, which can make a significant step in the sensing field based on crystalline COFs., 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.)

Purpose: The purpose of this study was to investigate the correlation between podocyte related biomarker cofilin-1 and renal function, and explore the value of cofilin-1 in predicting the risk of renal adverse prognosis in IgA nephropathy (IgAN)., Methods: Patients with primary IgAN diagnosed by initial renal biopsy performed in our hospital from January 2019 to February 2022 were included. This study was a prospective cohort study. All IgAN patients were detected the expression of cofilin-1 and other related biomarkers (RhoA, NGAL) in urine by enzyme-linked immunosorbent assay (ELISA) and follow-up at least 6 months. We also collected baseline clinicopathologial data of IgAN. The decreased renal function group was defined as baseline eGFR < 60 ml/min/1.73m 2 . Logistic and Cox regression model were used to analyze the correlation among cofilin-1 and renal prognosis., Results: 133 IgAN patients were included, with a male-to-female ratio of 1.25:1 and an age of 37.67 ± 13.78 years, as well as an average of eGFR was 71.63 (40.42,109.33) ml/min/1.73m 2 . 56 patients (42.1%) had decreased renal function at baseline, with the average of eGFR was 34.07 (16.72, 49.21) ml/min/1.73 m 2 . 12 of which developed to renal adverse prognosis. The average of follow-up time was 22.035 ± 8.992 months. The multivariate regression analysis showed that increased urinary cofilin-1 was an independent risk factor associated with baseline renal function decline and renal adverse prognosis in IgAN patients (P < 0.05). ROC curves showed great efficacy of urinary cofilin-1 levels in diagnosing baseline renal function decline and predicting renal adverse prognosis (the area under the ROC curve was 0.708 and 0.803)., Conclusion: Cofilin-1 as a novel biomarker of podocyte lesion is closely related to renal function decline in IgAN. Cofilin-1 has certain clinical value in predicting the risk of renal adverse prognosis. Podocyte fusion affects the renal prognosis of IgAN., (© 2024. The Author(s).)

Background: Post-hepatectomy liver failure (PHLF) is the most common postoperative complication and the leading cause of death after hepatectomy. The albumin-bilirubin (ALBI) score and nutritional risk index (NRI) have been shown to assess end-stage liver disease and predict PHLF and patient survival. We hypothesized that the ALBI score and NRI interact in the prediction of PHLF., Aim: To analyze the interaction between the ALBI score and NRI in PHLF in patients with hepatocellular carcinoma., Methods: This retrospective study included 186 patients who underwent hepatectomy for hepatocellular carcinoma at the Affiliated Hospital of Youjiang Medical University for Nationalities between January 2020 and July 2023. Data on patient characteristics and laboratory indices were collected from their medical records. Univariate and multivariate logistic regression were performed to determine the interaction effect between the ALBI score and NRI in PHLF., Results: Of the 186 patients included in the study, PHLF occurred in 44 (23.66%). After adjusting for confounders, multivariate logistic regression identified ALBI grade 2/3 [odds ratio (OR) = 73.713, 95% confidence interval (CI): 9.175-592.199] and NRI > 97.5 (OR = 58.990, 95%CI: 7.337-474.297) as risk factors for PHLF. No multiplicative interaction was observed between the ALBI score and NRI (OR = 0.357, 95%CI: 0.022-5.889). However, the risk of PHLF in patients with ALBI grade 2/3 and NRI < 97.5 was 101 times greater than that in patients with ALBI grade 1 and NRI ≥ 97.5 (95%CI: 56.445-523.839), indicating a significant additive interaction between the ALBI score and NRI in PHLF., Conclusion: Both the ALBI score and NRI were risk factors for PHLF, and there was an additive interaction between the ALBI score and NRI in PHLF., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Gastric cancer (GC) is the most common malignant tumor and ranks third for cancer-related deaths among the worldwide. The disease poses a serious public health problem in China, ranking fifth for incidence and third for mortality. Knowledge of the invasive depth of the tumor is vital to treatment decisions., Aim: To evaluate the diagnostic performance of double contrast-enhanced ultrasonography (DCEUS) for preoperative T staging in patients with GC by comparing with multi-detector computed tomography (MDCT)., Methods: This single prospective study enrolled patients with GC confirmed by preoperative gastroscopy from July 2021 to March 2023. Patients underwent DCEUS, including ultrasonography (US) and intravenous contrast-enhanced ultrasonography (CEUS), and MDCT examinations for the assessment of preoperative T staging. Features of GC were identified on DCEUS and criteria developed to evaluate T staging according to the 8 th edition of AJCC cancer staging manual. The diagnostic performance of DCEUS was evaluated by comparing it with that of MDCT and surgical-pathological findings were considered as the gold standard., Results: A total of 229 patients with GC (80 T1, 33 T2, 59 T3 and 57 T4) were included. Overall accuracies were 86.9% for DCEUS and 61.1% for MDCT ( P < 0.001). DCEUS was superior to MDCT for T1 (92.5% vs 70.0%, P < 0.001), T2 (72.7% vs 51.5%, P = 0.041), T3 (86.4% vs 45.8%, P < 0.001) and T4 (87.7% vs 70.2%, P = 0.022) staging of GC., Conclusion: DCEUS improved the diagnostic accuracy of preoperative T staging in patients with GC compared with MDCT, and constitutes a promising imaging modality for preoperative evaluation of GC to aid individualized treatment decision-making., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Rationale and Objectives: To develop a monitoring model using radiomics analysis based on longitudinal B-mode ultrasound (BUS) and shear wave elastography (SWE) to early predict pathological response to neoadjuvant chemotherapy (NAC) in breast cancer patients., Materials and Methods: In this prospective study, 112 breast cancer patients who received NAC between September 2016 and March 2022 were included. The BUS and SWE data of breast cancer were obtained prior to treatment as well as after two and four cycles of NAC. Radiomics features were extracted followed by measuring the changes in radiomics features compared to baseline after the second and fourth cycles of NAC (△R [C2], △R [C4]), respectively. The delta radiomics signatures were established using a support vector machine classifier., Results: The area under receiver operating characteristic curve (AUC) values of △R BUS (C2) and △R BUS (C4) for predicting the response to NAC were 0.83 and 0.84, while those of △R SWE (C2) and △R SWE (C4) were 0.88 and 0.90, respectively. △R SWE exhibited significantly superior performance to △R BUS for predicting NAC response (Delong test, p < 0.01). No significant differences were observed in the performances between △R (C2) and △R (C4) based on BUS or SWE data. The longitudinal dual-modal ultrasound radiomics (LDUR) model had an excellent discrimination, good calibration and clinical usefulness, with the AUC, sensitivity and specificity of 0.97, 95.52% and 91.11%, respectively., Conclusion: The LDUR model achieved excellent performance in predicting the pathological response to chemotherapy during the early stages of NAC for breast cancer., 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 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Objective: This study examined changes in wound symptoms and the health-related quality of life (HRQoL) of patients with newly diagnosed malignant fungating wounds, and explored the factors that impacted the changes in HRQoL., Method: This prospective longitudinal study included patients from three hospitals in China who had been diagnosed with malignant fungating wounds. Questionnaires were used to assess patients' HRQoL and their wound symptoms at the time of diagnosis (T0), as well as at one, three and six (T1, T2 and T3, respectively) months following the treatment period. Factors related to changes in HRQoL were analysed using generalised estimating equation models., Results: A total of 162 patients were included in the study. The patients reported low overall HRQoL. In three health-related dimensions (functional status, social relations and mental health), patients reported lower functional status at the time of wound diagnosis (T0), which then increased slowly with treatment over time. A lower QoL was associated with odour, exudate, bleeding, pruritus, a low performance status and the need for the dressing of wounds., Conclusion: The HRQoL of patients with malignant fungating wounds exhibited significant changes across different periods. It is thus of great importance to formulate pragmatic, patient and family-centred palliative wound care management strategies.

Copper ions (Cu 2+ ) play an essential role in various cellular functions, including respiration, nerve conduction, tissue maturation, oxidative stress defense, and iron metabolism. Covalent organic frameworks (COFs) are a class of porous crystalline materials with directed structural designability and high stability due to the combination of different monomers through covalent bonds. In this study, we synthesized a porphyrin-tetrathiazole COF (TT-COF(Zn)) with Zn-porphyrin and tetrathiafulvalene (TTF) as monomers and used it as a photoactive material. The strong light absorption of metalloporphyrin and the electron-rich properties of supplied TTF contribute to its photoelectrochemical performance. Additionally, the sulfur (S) in the TTF can coordinate with Cu 2+ . Based on these properties, we constructed a highly sensitive photoelectrochemical sensor for detecting Cu 2+ . The sensor exhibited a linear range from 0.5 nM to 500 nM ( R 2 = 0.9983) and a detection limit of 0.15 nM for Cu 2+ . Notably, the sensor performed well when detecting Cu 2+ in water samples.

Approximately 20% of colorectal cancer (CRC) patients present with metastasis at diagnosis. Among Stage I-III CRC patients who undergo surgical resection, 18% typically suffer from distal metastasis within the first three years following initial treatment. The median survival duration after the diagnosis of metastatic CRC (mCRC) is only 9 mo. mCRC is traditionally considered to be an advanced stage malignancy or is thought to be caused by incomplete resection of tumor tissue, allowing cancer cells to spread from primary to distant organs; however, increasing evidence suggests that the mCRC process can begin early in tumor development. CRC patients present with high heterogeneity and diverse cancer phenotypes that are classified on the basis of molecular and morphological alterations. Different genomic and nongenomic events can induce subclone diversity, which leads to cancer and metastasis. Throughout the course of mCRC, metastatic cascades are associated with invasive cancer cell migration through the circulatory system, extravasation, distal seeding, dormancy, and reactivation, with each step requiring specific molecular functions. However, cancer cells presenting neoantigens can be recognized and eliminated by the immune system. In this review, we explain the biological factors that drive CRC metastasis, namely, genomic instability, epigenetic instability, the metastatic cascade, the cancer-immunity cycle, and external lifestyle factors. Despite remarkable progress in CRC research, the role of molecular classification in therapeutic intervention remains unclear. This review shows the driving factors of mCRC which may help in identifying potential candidate biomarkers that can improve the diagnosis and early detection of mCRC cases., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Sensitive and convenient determination of gallic acid (GA) is vital for food safety. Here, a novel porphyrin (Cu)-based covalent organic framework named as COF(Cu) was successfully synthesized by condensing pre-metalated 5,10,15,20-tetrakis (para-aminophenyl) porphyrin copper (II) and 2,3,6,7-tetra (4-formylphenyl) tetrathiafulvalene ligands. By combining the advantages of porphyrin with tetrathiafulvalene, it may be possible to create a COF with an intrinsically effective charge-transfer channel. In addition, the Cu-N 4 type in the COF(Cu) can be regarded as the single-site electrocatalyst. Benefiting from these advantages, the COF(Cu) based electrochemical sensor demonstrated outstanding response to gallic acid (GA). Under the optimal conditions by square wave voltammetry technique, the COF(Cu) modified electrode showed a wide linear range (0.01-1000 μM), a low detection limit (2.81 nM), good reproducibility, acceptable selectivity as well as high stability. Moreover, the established approach was adopted to detect GA in real tea samples with good recoveries, indicating that the COF(Cu) based electrochemical sensor may pave the way for the application in food analysis., 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 © 2023 Elsevier B.V. All rights reserved.)

HLA-A*02:405 differs from HLA-A*02:06:01:01 by one nucleotide substitution in codon 161 in exon 3., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Rationale and Objectives: To carry out radiomics analysis/deep convolutional neural network (CNN) based on B-mode ultrasound (BUS) and shear wave elastography (SWE) to predict response to neoadjuvant chemotherapy (NAC) in breast cancer patients., Materials and Methods: In this prospective study, 255 breast cancer patients who received NAC between September 2016 and December 2021 were included. Radiomics models were designed using a support vector machine classifier based on US images obtained before treatment, including BUS and SWE. And CNN models also were developed using ResNet architecture. The final predictive model was developed by combining the dual-modal US and independently associated clinicopathologic characteristics. The predictive performances of the models were assessed with five-fold cross-validation., Results: Pretreatment SWE performed better than BUS in predicting the response to NAC for breast cancer for both the CNN and radiomics models (P < 0.001). The predictive results of the CNN models were significantly better than the radiomics models, with AUCs of 0.72 versus 0.69 for BUS and 0.80 versus 0.77 for SWE, respectively (P = 0.003). The CNN model based on the dual-modal US and molecular data exhibited outstanding performance in predicting NAC response, with an accuracy of 83.60% ± 2.63%, a sensitivity of 87.76% ± 6.44%, and a specificity of 77.45% ± 4.38%., Conclusion: The pretreatment CNN model based on the dual-modal US and molecular data achieved excellent performance for predicting the response to chemotherapy in breast cancer. Therefore, this model has the potential to serve as a non-invasive objective biomarker to predict NAC response and aid clinicians with individual treatments., 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 © 2023 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

The information tranfered among individual animals can be shared by a network, which is consisted of the sender, the receiver, and the extra bystander of the communication signals. The bystanders can read and use the signal that is not sent directly to them and make use of it to interfere with the sender and the receiver, which is known as "audience effects" in the research area of animal behaviors. The processes of mate choice and mating of animals occur mainly in the network that is composed of the particular species. Increasing evidence show that the audience effects play an important role in regulating mating preference and mating strategy, resulting in changes in species evolution. Here, we review the role of audience effects on animal mate choice and evolution by clarifying the definition and functional explanations of audience effects, the factors contributing to audience effects, as well as the different impacts of audience effects on males and females. It would provide novel ideas to study the impacts of audience effects on mate choice and species evolution in the future.

ZnO/TiO 2 catalysts with different ZnO contents have been prepared through equal volume impregnation method, characterized by XRD, SEM, Py-IR, ICP, XPS, NH 3 -TPD and N 2 adsorption/desorption, and evaluated in the synthesis of polycarbonate diol (PCDL) through transesterification. The results showed that titanium zinc oxide formed in these catalysts, and the content of acidic sites varied with the ZnO content, and ZnO/TiO 2 (10%) has the highest acid amount. The ZnO/TiO 2 (20%) with medium acidic sites showed the highest catalytic activity. The synthesis process of polycarbonate glycol was also optimized. Under the optimal reaction conditions, the yield of PCDL was 72.5%, and the M n reached 4829 g mol -1 with a PDI of 1.6., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

This study aims to observe the effect of chlorogenic acid(CGA) on microRNA(miRNA) in the process of protecting against N-acetyl-p-aminophenol(APAP)-induced liver injury. Eighteen C57BL/6 mice were randomly assigned into a normal group, a model group(APAP, 300 mg·kg~(-1)), and a CGA(40 mg·kg~(-1)) group. Hepatotoxicity of mice was induced by intragastric administration of APAP(300 mg·kg~(-1)). The mice in the CGA group were administrated with CGA(40 mg·kg~(-1)) by gavage 1 h after APAP administration. The mice were sacrificed 6 h after APAP administration, and plasma and liver tissue samples were collected for the determination of serum alanine/aspartate aminotransferase(ALT/AST) level and observation of liver histopathology, respectively. MiRNA array combined with real-time PCR was employed to discover important miRNAs. The target genes of miRNAs were predicted via miRWalk and TargetScan 7.2, verified by real-time PCR, and then subjected to functional annotation and signaling pathway enrichment. The results showed that CGA administration lowered the serum ALT/AST level elevated by APAP and alleviate the liver injury. Nine potential miRNAs were screened out from the microarray. The expression of miR-2137 and miR-451a in the liver tissue was verified by real-time PCR. The expression of miR-2137 and miR-451a was significantly up-regulated after APAP administration, and such up-regulated expression was significantly down-regulated after CGA administration, consistent with the array results. The target genes of miR-2137 and miR-451a were predicted and verified. Eleven target genes were involved in the process of CGA protecting against APAP-induced liver injury. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment with DAVID and R language showed that the 11 target genes were enriched in Rho protein-related signal transduction, vascular patterning-related biological processes, binding to transcription factors, and Rho guanyl-nucleotide exchange factor activity. The results indicated that miR-2137 and miR-451a played an important role in the inhibition of CGA on APAP-induced hepatotoxicity.

The discovery and in-depth study of non-biocatalytic applications of active biomolecules are essential for the development of biomimicry. Here, the effect of intermolecular hydrogen-bonding traction on the CO 2 photoactivation performance of adenine nucleobase by means of an adenine-containing model system (AMOF-1-4) is uncovered. Remarkably, the hydrogen-bonding schemes around adenines are regularly altered with the increase in the alkyl (methyl, ethyl, isopropyl, and tert-butyl) electron-donating capacity of the coordinated aliphatic carboxylic acids, and thus, lead to a stepwise improvement in CO 2 photoreduction activity. Density functional theory calculations demonstrate that strong intermolecular hydrogen-bonding traction surrounding adenine can obviously increase the adenine-CO 2 interaction energy and, therefore, result in a smoother CO 2 activation process. Significantly, this work also provides new inspiration for expanding the application of adenine to more small-molecule catalytic reactions., (© 2022 Wiley-VCH GmbH.)

Objective: To determine the ability of conventional ultrasound (US) combined with shear wave elastography (SWE) to reveal axillary status after neoadjuvant chemotherapy (NAC) in breast cancer patients., Methods: From September 2016 to December 2021, 201 patients with node-positive breast cancer who underwent NAC were enrolled in this prospective study. Conventional US features of axillary lymph nodes and SWE characteristics of breast lesions after NAC were analyzed. The diagnostic performances of US, SWE, and their combination were assessed using multivariate logistic regression and receiver operator characteristic curve (ROC) analyses., Results: The area under the ROC curve (AUC) for the ability of conventional US features to determine axillary status after NAC was 0.82, with a sensitivity of 85.23%, a specificity of 67.39%, and an accuracy of 76.11%. Shear wave velocity (SWV) displayed moderate performance for predicting axilla status after NAC with SWV mean demonstrating an AUC of 0.85. Cortical thickness and shape of axillary nodes and SWV mean of breast tumors were independently associated with axillary nodal metastasis after NAC. Compared to conventional US, the combination of conventional US of axillary lymph nodes with SWE of breast lesions achieved a significantly higher AUC (0.90 vs 0.82, p < 0.01, Delong's test) with a sensitivity of 87.50%, improved specificity of 82.61% and accuracy of 85.00%., Conclusions: Breast SWE was independently associated with residual metastasis of axillary node after NAC in patients with initially diagnosed positive axilla. Combining SWE with conventional US showed good diagnostic performance for axillary node disease after NAC., Key Points: • Breast SWE can serve as a supplement to axilla US for the evaluation of the axilla after NAC. • The combination of axilla US with breast SWE may be a promising method to facilitate less-invasive treatment in patients receiving NAC., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Temporomandibular disorder (TMD) is an umbrella term for pain and dysfunction of the temporomandibular joint (TMJ) and its associated structures. Patients with TMD show changes in TMJ kinematics and masticatory muscle activation. TMD is commonly comorbid with non-specific chronic neck pain (NCNP), which may be one of the risk factors for TMD., Objectives: This study aimed to investigate whether patients with NCNP have altered TMJ kinematics and masticatory muscle activity., Methods: This was a cross-sectional exploratory study including 19 healthy participants and 20 patients with NCNP but without TMD symptoms. TMJ kinematics was measured during mouth opening and closing, jaw protrusion and jaw lateral deviation. Surface electromyography was used to record the muscle activity of the anterior temporalis, masseter, sternocleidomastoid and upper trapezius while clenching. Furthermore, cervical posture, cervical range of motion (ROM) and pressure-pain threshold of the neck and masticatory muscles were measured., Results: Compared with the healthy group, the NCNP group showed significantly reduced upper cervical rotation ROM (p = .041) and increased condylar path length (p = .02), condylar translation (opening p = .034, closing p = .011) and mechanical pain sensitivity of the upper trapezius (p = .018). Increased condylar translation was significantly correlated with reduced upper cervical mobility and poor cervical posture (r = -0.322 to -0.397; p = .012-.046)., Conclusion: Increased condylar translation and path length in patients with NCNP may indicate poor control of TMJ articular movement, which may result from neck pain or may be a compensation for limited neck mobility. Evaluation of excessive TMJ translation may be considered in patients with NCNP., (© 2022 John Wiley & Sons Ltd.)

Background: Microwave ablation (MWA) is an effective treatment option for patients with primary liver cancer. However, it has been reported that the MWA procedure induces a hepatic inflammatory response and injury, which may negatively affect the efficacy of MWA. As such, the discovery of reliable markers to monitor the patient's response to MWA is needed. Golgi protein 73 (GP73) has been shown to be associated with chronic liver disease. To date, the potential value of serum GP73 in the dynamic monitoring during MWA of liver cancer remains unclear., Aim: To examine the effects of MWA on the serum levels of GP73 in patients with primary liver cancer., Methods: A total of 150 primary liver cancer patients with a single small lesion (≤ 3 cm in diameter) were retrospectively enrolled spanning the period between January 2016 and October 2018. All of the patients received MWA for the treatment of primary liver cancer. Serum GP73, alpha-fetoprotein (AFP), and widely used liver biochemical indicators [serum albumin, total bilirubin (TBIL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)] were compared before MWA and at different time points, including 1, 2, and 4 wk following the ablation procedure., Results: Complete tumor ablation was achieved in 95.33% of the patients at 1 mo after MWA. The 1-, 2-, and 3-year disease-free survival rates were 74.67%, 59.33%, and 54.00%, respectively. The serum AFP levels were significantly decreased at 1, 2, and 4 wk after MWA; they returned to the normal range at 12 wk after MWA; and they remained stable thereafter during follow-up in those cases without recurrence. In contrast, the serum GP73 levels were significantly increased at 1 and 2 wk after MWA. The serum GP73 levels reached the peak at 2 wk after MWA, started to decline after hepatoprotective treatment with glycyrrhizin and reduced glutathione, and returned to the pretreatment levels at 12 and 24 wk after MWA. Notably, the changes of serum GP73 in response to MWA were similar to those of TBIL, ALT, and AST., Conclusion: Serum GP73 is markedly increased in response to MWA of liver cancer. Thus, serum GP73 holds potential as a marker to monitor MWA-induced inflammatory liver injury in need of amelioration., Competing Interests: Conflict-of-interest statement: Xu ZJ has received research funding from the Military Medical Science and Technology Committee of China, No. 14MS095, and grants from the Quanzhou Science and Technology Planning Project, No. 2017Z018, during the conduct of the study., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: We sought to identify the absolute risk of specific HPV genotype for cervical intraepithelial neoplasia grade 2/3 or worse (CIN2+/3+) and to develop a risk-based management strategy in an HPV-positive population., Methods: HPV genotyping was performed based on a 3-year cervical cancer screening cohort. The study endpoints were histologic CIN2+/3+. The prevalence of specific HPV genotype was calculated by minimum, any type, and hierarchical attribution estimate. The absolute CIN2+/3+ risks of specific HPV genotype were estimated and risk-based management strategy was established according to the American Society for Colposcopy and Cervical Pathology guideline. The efficacy of conventional and risk-based management strategies for non-16/18 HPVs were further evaluated., Results: Eligible data were available for 8,370 women with a median age of 48 years (interquartile range, 42-53 years). At baseline, there were 1,062 women with HPV-positive disease, including 424 with multiple and 639 with single infections. CIN2+/3+ cases represented 113/74, 23/8, 20/7, and 52/31 patients at baseline and first-, second-, and third-year visits, respectively. Women with multiple HPV infections at baseline were more prone to persistent infection than those with single infection (P<.0001). HPV16 and HPV52 were the top 2 ranking among baseline and 3-year cumulative CIN2+/3+ cases. Based on the absolute risk of specific HPV genotype combined with cytology for CIN2+/3+, all non-16/18 HPVs were divided into 4 risk-stratified groups. Compared with conventional strategy, the risk-based strategy had higher specificity (P=.0000) and positive predictive value (P=.0322) to detect CIN3+ and needed fewer colposcopies for each CIN3+ case., Conclusions: Based on our study findings, we propose a new extended HPV genotyping protocol, which would provide a better strategy for achieving precise risk-based management of HPV-positive populations.

The rapid development of bioengineering technology has introduced Fc-fusion proteins, representing a novel kind of recombinant protein, as promising biopharmaceutical products in tumor therapy. Numerous related anti-tumor Fc-fusion proteins have been investigated and are in different stages of development. Fc-fusion proteins are constructed by fusing the Fc-region of the antibody with functional proteins or peptides. They retain the bioactivity of the latter and partial properties of the former. This structural and functional advantage makes Fc-fusion proteins an effective tool in tumor immunotherapy, especially for the recruitment and activation of natural killer (NK) cells, which play a critical role in tumor immunotherapy. Even though tumor cells have developed mechanisms to circumvent the cytotoxic effect of NK cells or induce defective NK cells, Fc-fusion proteins have been proven to effectively activate NK cells to kill tumor cells in different ways, such as antibody-dependent cell-mediated cytotoxicity (ADCC), activate NK cells in different ways in order to promote killing of tumor cells. In this review, we focus on NK cell-based immunity for cancers and current research progress of the Fc-fusion proteins for anti-tumor therapy by activating NK cells., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Glioblastoma multiform (GBM) is a highly aggressive primary brain tumor. Exosomes derived from glioma cells under a hypoxic microenvironment play an important role in tumor biology including metastasis, angiogenesis and chemoresistance. However, the underlying mechanisms remain to be elucidated. In this study, we aimed to explore the role of connexin 43 on exosomal uptake and angiogenesis in glioma under hypoxia. U251 cells were exposed to 3% oxygen to achieve hypoxia, and the expression levels of HIF-1α and Cx43, involved in the colony formation and proliferation of cells were assessed. Exosomes were isolated by differential velocity centrifugation from U251 cells under normoxia and hypoxia (Nor-Exos and Hypo-Exos), respectively. Immunofluorescence staining, along with assays for CCK-8, tube formation and wound healing along with a transwell assay were conducted to profile exosomal uptake, proliferation, tube formation, migration and invasion of HUVECs, respectively. Our results revealed that Hypoxia significantly up-regulated the expression of HIF-1α in U251 cells as well as promoting proliferation and colony number. Hypoxia also increased the level of Cx43 in U251 cells and in the exosomes secreted. The uptake of Dio-stained Hypo-Exos by HUVECs was greater than that of Nor-Exos, and inhibition of Cx43 by 37,43 gap27 or lenti-Cx43-shRNA efficiently prevented the uptake of Hypo-Exos by recipient endothelial cells. In addition, the proliferation and total loops of HUVECs were remarkably increased at 24 h, 48 h, and 10 h after Hypo-Exos, respectively. Notably, 37,43 gap27, a specific Cx-mimetic peptide blocker of Cx37 and Cx43, efficiently alleviated Hypo-Exos-induced proliferation and tube formation by HUVECs. Finally, 37,43 gap27 also significantly attenuated Hypo-Exos-induced migration and invasion of HUVECs. These findings demonstrate that exosomal Cx43 contributes to glioma angiogenesis mediated by Hypo-Exos, and suggests that exosomal Cx43 might serve as a potential therapeutic target for glioblastoma., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

A novel deep-ultraviolet and dual-emission carbon nanodots (DUCDs)-based dual-channel ratiometric probe was prepared by a one-pot environmental-friendly hydrothermal process using guanidine as the only starting material for sensing polyphenol in tea sample (TPPs). Under the exposure to TPPs, the DUCDs not only provided a characteristic colorimetric response to TPPs, but also displayed TPPs-sensitive ratiometric fluorescence quenching. The detection mechanism was proved to be that enrichment-specific hydroxyl sites (e.g., -NH 2 and -COOH) of DUCDs can specifically react with phenolic hydroxyl groups of TPPs to generate dynamic amide and carboxylate bonds by dehydration and/or condensation reaction. As a result, a new carbon nanomaterial with decrement of surface passivation groups, inherent light-absorbing, and invalid fluorescence emission was generated. The ratio (FL 297nm /FL 395nm ) of fluorescence intensity at 297 nm and 395 nm of DUCDs excited at 275 nm decreased with increasing TPPs concentration. The linearity range was 5.0 ng/mL to 100 µg/mL with a detection limit (DL) of 3.5 ± 0.04 ng/mL for TPPs (n = 3, 3σ/k). Colorimetry of DUCDs, best measured as absorbance at 320 nm, was increased linearly in the TPP concentration range 200 ng/mL-200 µg/mL with a DL of 94.7 ± 0.04 ng/mL (n = 3, 3σ/k). The probe was successfully applied to the determination of TPPs in real tea samples, showing potential application prospects in food analysis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

An electrochemical sensor for sensitive sensing of acyclovir (ACV) was designed by using the reduced graphene oxide-TiO 2 -Au nanocomposite-modified glassy carbon electrode (rGO-TiO 2 -Au/GCE). Transmission electron microscopy, X-ray diffractometer, and X-ray photoelectron spectroscopy were used to confirm morphology, structure, and composition properties of the rGO-TiO 2 -Au nanocomposites. Cyclic voltammetry and linear sweep voltammetry were used to demonstrate the analytical performance of the rGO-TiO 2 -Au/GCE for ACV. As a result, rGO-TiO 2 -Au/GCE exerted the best response for the oxidation of ACV under the pH of 6.0 PB solution, accumulation time of 80 s at open-circuit, and modifier amount of 7 µl. The oxidation peak currents of ACV increased linearly with its concentration in the range of 1-100 µM, and the detection limit was calculated to be 0.3 µM (S/N = 3). The determination of ACV concentrations in tablet samples also demonstrated satisfactory results., 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 © 2022 Lu, Li, Kong, Wei, Zhang, Li, Fang and Wang.)

Background: Declined cognitive function interferes with dual-task walking ability and may result in falls in older adults with mild cognitive impairment (MCI). The mind-body exercise, Tai Chi (TC), improves cognition and dual-task ability. Exergaming is low-cost, safe, highly scalable, and feasible. Whether the effects of exergaming-based TC is beneficial than traditional TC has not been investigated yet., Objectives: The objective of this study was to investigate effects of exergaming-based TC on cognitive function and dual-task walking among older adults with MCI., Methods: Fifty patients with MCI were randomly assigned to an exergaming-based TC (EXER-TC) group, a traditional TC (TC) group, or a control group. The EXER-TC and TC groups received 36 training sessions (three, 50-min sessions per week) during a 12-week period. The control group received no intervention and were instructed to maintain their usual daily physical activities. The outcome variables measured included those related to cognitive function, dual-task cost (DTC), and gait performance., Results: The EXER-TC and TC groups performed better than the control group on the Chinese version of the Stroop Color and Word Test, the Trail Making Test Parts A and B, the one-back test, gait speed, and DTC of gait speed in cognitive dual-task conditions after training. However, there were no significant differences between the EXER-TC and TC groups. Compared with the control group, only the EXER-TC group experienced beneficial effects for the Montreal Cognitive Assessment., Conclusion: EXER-TC was comparable to traditional TC for enhancement of dual-task gait performance and executive function. These results suggested that the EXER-TC approach has potential therapeutic use in older adults with MCI., 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 © 2022 Liu, Cheng, Wei and Liao.)

This study aimed to investigate the effects of selenium (Se) on the expression of Toll-like receptor (TLR) 2 and pyrin domain-containing protein (NLRP)3 inflammasome in macrophages infected by Staphylococcus aureus (S. aureus). RAW 264.7 macrophages were treated with 2 μmol/L Na 2 SeO 3 for 12 h before infection with S. aureus for 2 h. Through Western blot, qRT-PCR, and ELISA analysis, the core molecules of TLR2 signaling pathway and NLRP3 inflammasome in RAW 264.7 macrophages were detected. Results showed that Se significantly reduced the elevated mRNA expression of TLR2, myeloid differentiation factor-88 (Myd88), NLRP3, Caspase-recruitment domain (ASC), and Caspase-1 induced by S. aureus. Furthermore, compared with I group, the protein expression of TLR2, Myd88, NLRP3, ASC, and Caspase-1 were suppressed in T group. In addition, the mRNA and protein expression of interleukin-1 beta (IL-1β) induced by S. aureus were also decreased after Se treatment. In conclusion, Se inhibits S. aureus-induced inflammation by suppressing the activation of the TLR2 signaling pathway and NLRP3 inflammasome in RAW 264.7 macrophages., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rhododendron henanense subsp. lingbaoense is endemic in China. The cpDNA of R. henanense subsp. lingbaoense is a typical quadripartite structure with a length of 208,015 bp, including a large single-copy region of 110,593 bp and a small single-copy region of 2606 bp separated by a pair of identical inverted repeat regions of 47,408 bp each. The chloroplast genome contains 119 genes, including 86 protein-coding genes, four ribosomal RNA genes, and 29 transfer RNA genes. The phylogenetic analysis of R. henanense subsp. lingbaoense showed a relatively close relationship with Rhododendron delavayi ., Competing Interests: No potential conflict of interest was reported by the authors., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Uremic toxins (UTs) are mainly produced by protein metabolized by the intestinal microbiota and converted in the liver or by mitochondria or other enzymes. The accumulation of UTs can damage the intestinal barrier integrity and cause vascular damage and progressive kidney damage. Together, these factors lead to metabolic imbalances, which in turn increase oxidative stress and inflammation and then produce uremia that affects many organs and causes diseases including renal fibrosis, vascular disease, and renal osteodystrophy. This article is based on the theory of the intestinal-renal axis, from bench to bedside, and it discusses nonextracorporeal therapies for UTs, which are classified into three categories: medication, diet and supplement therapy, and complementary and alternative medicine (CAM) and other therapies. The effects of medications such as AST-120 and meclofenamate are described. Diet and supplement therapies include plant-based diet, very low-protein diet, probiotics, prebiotics, synbiotics, and nutraceuticals. The research status of Chinese herbal medicine is discussed for CAM and other therapies. This review can provide some treatment recommendations for the reduction of UTs in patients with chronic kidney disease.

Multidimensional fabrication of metal-organic frameworks (MOFs) into multilevel channel integrated devices are in high demanded for Li-S separators. Such separators have advantages in pore-engineering that might fulfill requirements such as intercepting the diffusing polysulfides and improving the Li + /electrolyte transfer in Li-S batteries. However, most reported works focus on the roles of MOFs as ionic sieves for polysulfides while offering limited investigation on the tuning of Li + transfer across the separators. A photoinduced heat-assisted processing strategy is proposed to fabricate MOFs into multidimensional devices (e.g., hollow/Janus fibers, double-or triple-layer membranes). For the first time, a triple-layer separator with stepped-channels has been designed and demonstrated as a powerful separator with outstanding specific capacity (1365.0 mAh g -1 ) and cycling performance (0.03 % fading per cycle from 100 th to 700 th cycle), which is superior to single/double-layer and commercial separators. The findings may expedite the development of MOF-based membranes and extend the scope of MOFs in energy-storage technologies., (© 2021 Wiley-VCH GmbH.)

Glioblastoma is the most common and aggressive brain tumor and it is characterized by a high mortality rate. Temozolomide (TMZ) is an effective chemotherapy drug for glioblastoma, but the resistance to TMZ has come to represent a major clinical problem, and its underlying mechanism has yet to be elucidated. In the present study, the role of exosomal connexin 43 (Cx43) in the resistance of glioma cells to TMZ and cell migration was investigated. First, higher expression levels of Cx43 were detected in TMZ‑resistant U251 (U251r) cells compared with those in TMZ‑sensitive (U251s) cells. Exosomes from U251s or U251r cells (sExo and rExo, respectively) were isolated. It was found that the expression of Cx43 in rExo was notably higher compared with that in sExo, whereas treatment with rExo increased the expression of Cx43 in U251s cells. Additionally, exosomes stained with dioctadecyloxacarbocyanine (Dio) were used to visualized exosome uptake by glioma cells. It was observed that the uptake of Dio‑stained rExo in U251s cells was more prominent compared with that of Dio‑stained sExo, while 37,43 Gap27, a gap junction mimetic peptide directed against Cx43, alleviated the rExo uptake by cells. Moreover, rExo increased the IC 50 of U251s to TMZ, colony formation and Bcl‑2 expression, but decreased Bax and cleaved caspase‑3 expression in U251s cells. 37,43 Gap27 efficiently inhibited these effects of rExo on U251s cells. Finally, the results of the wound healing and Transwell assays revealed that rExo significantly enhanced the migration of U251s cells, whereas 37,43 Gap27 significantly attenuated rExo‑induced cell migration. Taken together, these results indicate the crucial role of exosomal Cx43 in chemotherapy resistance and migration of glioma cells, and suggest that Cx43 may hold promise as a therapeutic target for glioblastoma in the future.

Background and Objective: At present, the deficiency of β-cell function is progressive in patients with type 2 diabetes mellitus. Exenatide cannot only control blood glucose well, but also promotes the regeneration and proliferation of islet β-cells and improves the function of β cells. However, it needs to be given twice a day, and there are many adverse reactions such as nausea. PEGylated exenatide (study code: PB-119) needs to be administered only once a week. The purpose of this experiment was to evaluate the safety, pharmacokinetics and pharmacodynamics of an escalating dose regimen of subcutaneous PEGylated exenatide injections in healthy subjects., Methods: Twelve healthy young adult subjects in each group received once-weekly subcutaneous injections of 165 μg, 330 μg, and 660 μg PEGylated exenatide for 6 weeks. Plasma drug concentration was determined in venous blood collected across selected time points. Safety and tolerability were evaluated by monitoring adverse events, laboratory parameters, and electrocardiogram. Blood glucose, insulin,  glucagon and C peptide were monitored at different time points to evaluate the pharmacodynamics of PEGylated exenatide., Results: A total of 11, 10, and 12 subjects completed the study in 165 µg, 330 µg, and 660 µg dose groups, respectively. After 6 consecutive weeks of administration, the t 1/2 in the 165 μg, 330 μg, and 660 µg dose groups was 55.67 ± 11.03 h, 56.99 ± 21.37 h, and 54.81 ± 13.87 h, respectively. The C avg was 4.22 ± 0.78 ng/ml, 6.03 ± 1.43 ng/ml, and 10.50 ± 3.06 ng/ml, respectively. AUCss was 708.59 ± 131.87 h•ng/ml, 1012.63 ± 240.79 h•ng/ml, and 1763.81 ± 514.50 h•ng/ml, respectively. The accumulation index was 1.15 ± 0.07, 1.17 ± 0.11, and 1.14 ± 0.07. The CLss/F was 241.25 ± 51.13 ml/h, 341.53 ± 73.62 ml/h, and 450.06 ± 313.76 ml/h, respectively. A total of 10 of 36 (27.78%) subjects in the three dose groups developed specific antibodies after consecutive subcutaneous injections of PEGylated exenatide. The C avg and C max were higher than those of antibody-negative subjects. Furthermore, in antibody-positive subjects, CLss/F, t 1/2 , AUC τ , accumulation index, MRT (0-inf) and other parameters were lower than those of antibody-negative subjects. In the 165 μg dose group, two subjects (16.67%) experienced 4 adverse events. In the 330 μg dose group, no subjects reported adverse events. In the 660 μg dose group, 8 subjects (66.67%) reported 16 adverse events, which were mostly gastrointestinal. There were no significant changes in the pharmacodynamic parameters except the glucagon level at day 36 in the 660 µg dose group, the 2h postprandial insulin and C peptide levels at day 36 and day 50 in the 165 μg dose group compared with baseline (- 1 day)., Conclusion: A once-weekly subcutaneous injection of 165 µg and 330 µg PEGylated exenatide is safe. No significant effects on blood glucose or pancreatic hormone levels were observed in the subjects within these dose groups. The pharmacokinetic parameters of PEGylated exenatide may be affected by immunogenicity., Clinical Trials Registration: The study is registered at clinicaltrials.gov (No. NCT03062774).

The mixed-ligand strategy is one of the important methods for preparing new materials and regulating the properties of materials. In this work, by introducing different auxiliary ligands (ALs), we have obtained a series of mixed-ligand uranyl complexes ( 1 - 6 ) from a flexible biphenyltetracarboxylic acid (H 4 bptc) with an adjustable orthogonal conformation and studied the influence of different organic base molecules on the coordination and assembly of H 4 bptc with a uranyl cation. It is found that the coordinated ALs, including 4,4'-bipyridine-1,1'-dioxide and 1,10-phenanthroline, partially occupy the coordination sites of the uranyl center and directly affect the molecular conformations and uranyl coordination of flexible bptc linkers. On the other hand, noncoordinated ALs such as protonated 4,4'-bipyridine ([H 2 (4,4'-bpy)] 2+ ) or dimethylammonium, which work as counterions in the form of encapsulated guests or hydrogen-bonded templates, also have a nonnegligible impact on the conformation and coordination of bptc linkers. Most interestingly, the AL-mediated evolution of uranyl coordination by the bptc linker and coordination geometry of the uranyl center is clearly observed, which suggests the adaptability of flexible bptc linkers to take suitable molecular configurations and uranyl coordination modes so as to adapt to the external regulator agents and varying environment. The physicochemical characterization of these uranyl compounds, especially photoluminescence, is addressed and discussed, and the results reveal that compound 5 has the potential to serve as a multifunctional radiation detection material for UV light and X-ray radiation.

Background: Recent studies have proved the important role of many oncogenic long non-coding RNAs (lncRNAs) in the progression of pancreatic cancer, but little is known about the mechanisms of tumor suppression in pancreatic cancer., Aim: To evaluate the function of tumor suppressor lncRNA C9orf139 in pancreatic cancer progression and to study the underlying mechanism., Methods: We assigned 54 patients with pancreatic ductal adenocarcinoma treated at our hospital to the patient group and 30 normal subjects undergoing physical examination to the control group. RT-qPCR was used to measure the relative expression of C9orf139 in the tissue and serum of patients, in an attempt to investigate the prognostic value of C9orf139 in pancreatic cancer patients. The luciferase reporter gene assay was performed to determine the interaction between C9orf139 and miR-663a. The biological function of C9orf139 was assessed by in vitro assays and in vivo subcutaneous tumor formation tests in animal models. To figure out the molecular mechanism of C9orf139 to act on miR-663a/Sox12, RNA pull-down, Western blot assay, RNA immunoprecipitation assay, and co-immunoprecipitation assay were performed., Results: C9orf139 level significantly increased in the tissue and serum of patients, which had clinical diagnostic value for pancreatic cancer. Patients with high C9orf139 expression had a higher risk of progressing to stage III + IV, lymph node metastasis, and poor differentiation. Cox regression analysis suggested that C9orf139, tumor-node-metastasis stage, and lymph node metastasis were independent prognostic factors in patients. The underlying mechanism of C9orf139 was that it promoted the growth of pancreatic cancer cells by modulating the miR-663a/Sox12 axis., Conclusion: C9orf139 is highly expressed in pancreatic cancer, qualified to be used as a potential diagnostic and prognostic marker for pancreatic cancer. Its promotion of pancreatic cancer cell growth is achieved by mediating the miR-663a/Sox12 axis., Competing Interests: Conflict-of-interest statement: All the authors have no conflict of interest related to the manuscript., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Inflammatory response mediated by microglia plays a key role in cerebral ischemia-reperfusion injury. This study intends to probe the role of lncRNA SNHG4 in regulating the inflammatory response of the microglia during cerebral ischemia reperfusion., Materials and Methods: Blood samples and cerebrospinal fluid samples were collected from acute cerebral infarction (ACI) patients and healthy controls. The middle cerebral artery occlusion (MCAO) models were constructed with rats. LPS induction and oxygen-glucose deprivation methods were respectively applied to simulate the activation of microglia in vitro. qRT-PCR was employed to determine the expressions of SNHG4, miR-449c-5p and related inflammatory factors in vivo and in vitro. The inflammatory responses of the microglia subject to the varied expressions of SNHG4 and miR-449c-5p were detected. Luciferase assays were conducted to verify the crosstalk involving SNHG4, miR-449c-5p and STAT6., Results: Compared with the control group, the expression of SNHG4 derived from the samples of ACI patients and the microglia of MCAO group were remarkably down-regulated, but the expression of miR-449c-5p was dramatically up-regulated. Overexpression of SNHG4 and knock-down of miR-449c-5p could inhibit the expression of pro-inflammatory cytokine in the microglia and promote the expression of anti-inflammatory factors. Meanwhile, the phospho-STAT6 was up-regulated, whereas the knock-down of SNHG4 and over-expression of miR-449c-5p in microglia had the opposite effects. Luciferase assay confirmed that SNHG4 could target miR-449c-5p, while miR-449c-5p could target STAT6., Conclusion: SNHG4 can regulate STAT6 and repress inflammation by adsorbing miR-449c-5p in microglia during cerebral ischemia-reperfusion injury., Competing Interests: The authors declare that they have no competing interests., (© 2020 Zhang et al.)

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide and 30% of patients with CRC experience metastasis. Patients with metastatic colorectal cancer (mCRC) have a 5-year overall survival rate of <10%. V-raf murine sarcoma viral oncogene homolog B1 ( BRAF ) and V-Ki-ras2 Kirsten ratsarcoma viral oncogene homolog ( KRAS ) mutations are mostly studied in mCRC, as clinical trials found that first-line chemotherapy with anti-epidermal growth factor receptor agent confers limited efficacy for mCRC. Treatment decisions for early-stage mCRC do not consider BRAF or KRAS mutations, given the dramatically poor prognosis conferred by these mutations in clinical trials. Thus, it is necessary to identify patients with mCRC harboring BRAF or KRAS mutations to formulate rational therapeutic strategies to improve prognosis and survival. BRAF and KRAS mutations occur in ∼10% and ∼44% of patients with mCRC, respectively. Although the survival rate of patients with mCRC has improved in recent years, the response and prognosis of patients with the aforementioned mutations are still poor. There is a substantial unmet need for prospective personalized therapies for patients with BRAF - or KRAS -mutant mCRC. In this review, we focus on BRAF and KRAS mutations to understand the mechanisms underlying resistance and improving the response rate, outcomes, and prognosis of patients with mCRC bearing these mutations and to discuss prospective personalized therapies for BRAF - and KRAS -mutant mCRC., (© The Author(s) 2020. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

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Background and Objective: Exenatide promotes insulin secretion and inhibits postprandial glucagon secretion. Polyethylene glycolated exenatide injection (PB-119), a derivative obtained by modification of exenatide, is more stable in metabolic behavior than exenatide in vivo. Our study aimed to evaluate the safety, tolerability and pharmacokinetic characteristics of polyethylene glycolated exenatide as a single subcutaneous injection in healthy volunteers., Methods: Seventy subjects were randomly assigned to 8 incremental dosage groups (2, 5, 10, 25, 50, 100, 200 and 400 µg). The 2- to 50-µg groups had 8 subjects in each group (the ratio of test preparation to placebo was 3:1), and the 100- to 400-µg groups had 10 subjects in each group (the ratio of test preparation to placebo was 4:1). All the subjects received a single subcutaneous injection of polyethylene glycolated exenatide and placebo according to the dosage groups. The tolerability test was conducted in the 2- to 10-µg groups. The pharmacokinetic test was carried out in the 25- to 400-µg groups, and plasma samples were collected to determine the pharmacokinetics of polyethylene glycolated exenatide. After medication, the vital signs of the subjects were monitored, and laboratory tests and electrocardiogram tests were carried out regularly in all the subjects., Results: All 70 subjects completed the experiment. Except for the 5-µg and 10-µg groups, the safety and tolerability tests showed no adverse reactions in the 2-µg to 50-µg groups. Several subjects in the 100-µg and 200-µg groups had tolerable gastrointestinal tract reactions, and all subjects in the 400-µg group experienced adverse reactions, mainly gastrointestinal tract reactions and liver dysfunction. The pharmacokinetics of polyethylene glycolated exenatide was studied in 36 subjects, which showed slow absorption, a mean peak time of 20-40 h, and a mean elimination half-life of 51-64 h., Conclusion: The administration of polyethylene glycolated exenatide injection at a single dose of 2-200 µg is safe and tolerable for healthy volunteers. Once-weekly polyethylene glycolated exenatide injection can be recommended., Clinical Trials Registration: The study was registered at clinicaltrials.gov (No. NCT02084251).

A nanocage coupling effect from a redox Ru II -Pd II metal-organic cage (MOC-16) is demonstrated for efficient photochemical H 2 production by virtue of redox-guest modulation of the photo-induced electron transfer (PET) process. Through coupling with photoredox cycle of MOC-16, tetrathiafulvalene (TTF) guests act as electron relay mediator to improve the overall electron transfer efficiency in the host-guest system in a long-time scale, leading to significant promotion of visible-light driven H 2 evolution. By contrast, the presence of larger TTF-derivatives in bulk solution without host-guest interactions results in interference with PET process of MOC-16, leading to inefficient H 2 evolution. Such interaction provides an example to understand the interplay between the redox-active nanocage and guest for optimization of redox events and photocatalytic activities in a confined chemical nanoenvironment., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Previous studies report that (-)-epigallocatechin-3-gallate (EGCG), the most abundant polyphenolic ingredient in green tea, has high efficacy against Alzheimer's disease (AD) in various in vivo and in vitro models. However, as a water-soluble component, how EGCG exerts its anti-AD effects in the brain was not elucidated. In the present study, we investigated the anti-AD mechanisms of EGCG in natural aging rats with cognitive impairments (CIs) assessed using Morris water maze. The rats were treated with EGCG (100 mg/kg per day, intragastrically) for 4 weeks. The expression of β-amyloid (Aβ 1-42 ) in the brain was detected with immunohistochemical staining. We showed that EGCG administration significantly ameliorated the CI in the aging rats with CI and decreased Aβ 1-42 plaque formation in their brains. Then we used an efficient ultra-performance liquid chromatography-tandem mass spectrometer method to evaluate EGCG concentrations in rat plasma and tissue distribution. We found that EGCG absorption was significantly increased in the aging with CI group compared with control young rats. After oral administration of EGCG (100 mg), EGCG could not be detected in the brain tissues of control young rats, but it was found in the brain tissue of aging rats with CI. By using Evans Blue assay, transmission electron microscopy, and Western blotting assay, we demonstrated that the permeability of blood-brain barrier (BBB) was significantly increased in aging rats with CI. These results suggest that the permeability change of BBB is the physiological structural basis for EGCG treatment to improve learning and memory, thus providing a solid evidence for EGCG druggability in anti-AD therapeutic field.

Neurodegenerative diseases (NDs) are characterized by the progressive loss of structure and function of neurons most common in elderly population, mainly including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). Neuroinflammation caused by microglia as the resident macrophages of the central nervous system (CNS) plays a contributory role in the onset and progression of NDs. Activated microglia, as in macrophages, to be heterogeneous, can polarize into M1 (pro-inflammatory) and M2 (anti-inflammatory) functional phenotypes. The former elaborate pro-inflammatory mediators promoting neuroinflammation and neuronal damage. In contrast, the latter generate anti-inflammatory mediators and neurotrophins that inhibit neuroinflammation and promote neuronal healing. Consistently, the regulation of microglial polarization from M1 to M2 phenotype appears as an outstanding therapeutic and preventive approach for NDs treatment. Although non-steroidal anti-inflammatory drugs (NSAIDs) currently used to alleviate M1 microglia-associated neuroinflammation responsible for the development of NDs, these drugs have different degrees of adverse effects and limited efficacy. As the advantages of novel structure, multi-target, high efficiency and low toxicity, natural products as the modulators of microglial polarization have attracted considerable concerns in the therapeutic areas of NDs. In this review, we mainly summarized the therapeutic potential of natural products and their various molecular mechanisms for NDs treatment through modulating microglial polarization. The aim of the current review is expected to be useful to develop innovative modulators of microglial polarization from natural products for the amelioration and treatment of NDs., (Copyright © 2019 Elsevier Ltd. All rights reserved.)