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Objective: To evaluate the value of the malignant subregion-based texture analysis in predicting Ki-67 status in breast cancer., Materials and Methods: The dynamic contrast-enhanced magnetic resonance imaging data of 119 histopathologically confirmed breast cancer patients (81 patients with high Ki-67 expression status) from January 2018 to February 2023 in our hospital were retrospectively collected. According to the enhancement curve of each voxel within the tumor, three subregions were divided: washout subregion, plateau subregion, and persistent subregion. The washout subregion and the plateau subregion were merged as the malignant subregion. The texture features of the malignant subregion were extracted using Pyradiomics software for texture analysis. The differences in texture features were compared between the low and high Ki-67 expression cohorts and then the receiver operating characteristic (ROC) curve analysis to evaluate the predictive performance of texture features on Ki-67 expression. Finally, a support vector machine (SVM) classifier was constructed based on differential features to predict the expression level of Ki-67, the performance of the classifier was evaluated using ROC analysis and confirmed using 10-fold cross-validation., Results: Through comparative analysis, 51 features exhibited significant differences between the low and high Ki-67 expression cohorts. Following feature reduction, 5 features were selected to build the SVM classifier, which achieved an area under the ROC curve (AUC) of 0.77 (0.68-0.87) for predicting the Ki-67 expression status. The accuracy, sensitivity, and specificity were 0.76, 0.80, and 0.68, respectively. The average AUC from the 10-fold cross-validation was 0.72 ± 0.14., Conclusion: The texture features of the malignant subregion in breast cancer were potential biomarkers for predicting Ki-67 expression level in breast cancer, which might be used to precisely diagnose and guide the treatment of breast cancer., 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 Hua, Wenwen, Huijuan, Ting and Jin.)

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC., Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821., Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group., Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile., Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project., Competing Interests: We declare no competing interests., (© 2024 Published by Elsevier Ltd.)

Root architecture and function are critical for plants to secure water and nutrient supply from the soil, but environmental stresses alter root development. The phytohormone jasmonic acid (JA) regulates plant growth and responses to wounding and other stresses, but its role in root development for adaptation to environmental challenges had not been well investigated. We discovered a novel JA Upregulated Protein 1 gene (JAUP1) that has recently evolved in rice and is specific to modern rice accessions. JAUP1 regulates a self-perpetuating feed-forward loop to activate the expression of genes involved in JA biosynthesis and signalling that confers tolerance to abiotic stresses and regulates auxin-dependent root development. Ectopic expression of JAUP1 alleviates abscisic acid- and salt-mediated suppression of lateral root (LR) growth. JAUP1 is primarily expressed in the root cap and epidermal cells (EPCs) that protect the meristematic stem cells and emerging LRs. Wound-activated JA/JAUP1 signalling promotes crosstalk between the root cap of LR and parental root EPCs, as well as induces cell wall remodelling in EPCs overlaying the emerging LR, thereby facilitating LR emergence even under ABA-suppressive conditions. Elevated expression of JAUP1 in transgenic rice or natural rice accessions enhances abiotic stress tolerance and reduces grain yield loss under a limited water supply. We reveal a hitherto unappreciated role for wound-induced JA in LR development under abiotic stress and suggest that JAUP1 can be used in biotechnology and as a molecular marker for breeding rice adapted to extreme environmental challenges and for the conservation of water resources., (© 2024 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Background: Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial., Objective: To evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia., Methods: MIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12-75 years with severe asthma receiving medium-to-high-dose inhaled corticosteroid/long-acting β 2 -agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/μL; <300/μL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 second (pre-BD FEV 1 ) and total asthma symptom score (TASS). Safety was evaluated ≤ Week 56., Results: Of 695 patients randomized, 473 had baseline bEOS ≥300/μL (benralizumab n = 236; placebo n = 237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], p < 0.0001) and significantly improved pre-BD FEV 1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], p < 0.0001) and TASS (LSD -0.25 [-0.45, -0.05], p = 0.0126) versus placebo. In patients with baseline bEOS <300/μL, there were numerical improvements in AAER, pre-BD FEV 1 , and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population., Conclusions: MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Nanshan Zhong reports financial support was provided by AstraZeneca. Kefang Lai reports financial support was provided by AstraZeneca. Dejun Sun reports financial support was provided by AstraZeneca. Ranran Dai reports financial support was provided by AstraZeneca. Ronnie Samoro reports financial support was provided by AstraZeneca. Hae-Sim Park reports financial support was provided by AstraZeneca. Annika Astrand reports a relationship with AstraZeneca that includes: employment and equity or stocks. David Cohen reports a relationship with AstraZeneca that includes: employment and equity or stocks. Maria Jison reports a relationship with AstraZeneca that includes: employment and equity or stocks. Vivian H Shih reports a relationship with AstraZeneca that includes: employment and equity or stocks. Viktoria Werkstrom reports a relationship with AstraZeneca that includes: employment and equity or stocks. Yuhui Yao reports a relationship with AstraZeneca that includes: employment and equity or stocks. Yajuan Zhang reports a relationship with AstraZeneca that includes: employment and equity or stocks. Wenying Zheng reports a relationship with AstraZeneca that includes: employment and equity or stocks. Tanya Jandu and Helen Brereton of inScience Communications, Springer Healthcare Ltd, UK, provided medical writing support, which was funded by AstraZeneca. If there are other authors, they 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.)

Background and Purpose: Intracranial plaque enhancement (IPE) identified by contrast-enhanced vessel wall MR imaging (VW-MR imaging) is an emerging marker of plaque instability related to stroke risk, but there was no standardized timing for postcontrast acquisition. We aim to explore the optimal postcontrast timing by using multiphase contrast-enhanced VW-MR imaging and to test its performance in differentiating culprit and nonculprit lesions., Materials and Methods: Patients with acute ischemic stroke due to intracranial plaque were prospectively recruited to undergo VW-MR imaging with 1 precontrast phase and 4 consecutive postcontrast phases (9 minutes and 13 seconds for each phase). The signal intensity (SI) values of the CSF and intracranial plaque were measured on 1 precontrast and 4 postcontrast phases to determine the intracranial plaque enhancement index (PEI). The dynamic changes of the PEI were compared between culprit and nonculprit plaques on the postcontrast acquisitions., Results: Thirty patients with acute stroke (aged 59 ± 10 years, 18 [60%] men) with 113 intracranial plaques were included. The average PEI of all intracranial plaques significantly increased (up to 14%) over the 4 phases. There was significantly increased PEI over the 4 phases for culprit plaques (an average increase of 23%), but this was not observed for nonculprit plaques. For differentiating culprit and nonculprit plaques, we observed that the performance of IPE in the second postcontrast phase (cutoff = 0.83, AUC = 0.829 [0.746-0.893]) exhibited superior accuracy when compared with PEI in the first postcontrast phase (cutoff = 0.48; AUC = 0.768 [0.680-0.843]) ( P = .022)., Conclusions: A 9-minute delay of postcontrast acquisition can maximize plaque enhancement and better differentiate between culprit and nonculprit plaques. In addition, culprit and nonculprit plaques have different enhancement temporal patterns, which should be evaluated in future studies., (© 2024 by American Journal of Neuroradiology.)

Aim: Liver fibrosis remains a great challenge in the world. Spinosin (SPI), a natural flavonoid-C-glycoside, possesses various pharmacological activities including anti-inflammatory and anti-myocardial fibrosis effects. In this study, we investigate whether SPI can be a potential lead for the treatment of liver fibrosis and explore whether the orphan nuclear receptor Nur77, a negative regulator of liver fibrosis development, plays a critical role in SPI's action., Methods: A dual luciferase reporter system of α-SMA was established to evaluate the effect of SPI on hepatic stellate cell (HSC) activation in LX2 and HSC-T6 cells. A mouse model of CCl 4 -induced liver fibrosis was used to test the efficacy of SPI against liver fibrosis. The expression levels of Nur77, inflammatory cytokines and collagen were determined by Western blotting and qPCR. Potential kinase pathways involved were also analyzed. The affinity of Nur77 with SPI was documented by fluorescence titration., Results: SPI can strongly suppress TGF-β1-mediated activation of both LX2 and HSC-T6 cells in a dose-dependent manner. SPI increases the expression of Nur77 and reduces TGF-β1-mediated phosphorylation levels of ASK1 and p38 MAPK, which can be reversed by knocking out of Nur77. SPI strongly inhibits collagen deposition (COLA1) and reduces inflammatory cytokines (IL-6 and IL-1β), which is followed by improved liver function in the CCl 4 -induced mouse model. SPI can directly bind to R515 and R563 in the Nur77-LBD pocket with a Kd of 2.14 μM., Conclusion: Spinosin is the major pharmacological active component of Ziziphus jujuba Mill. var. spinosa which has been frequently prescribed in traditional Chinese medicine. We demonstrate here for the first time that spinosin is a new therapeutic lead for treatment of liver fibrosis by targeting Nur77 and blocking the ASK1/p38 MAPK signaling pathway., Competing Interests: Declaration of competing interest 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 Elsevier B.V. All rights reserved.)

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management., (© 2023. Asian Pacific Association for the Study of the Liver.)

Liver fibrosis remains a global health challenge due to its rapidly rising prevalence and limited treatment options. The orphan nuclear receptor Nur77 has been implicated in regulation of autophagy and liver fibrosis. Targeting Nur77-mediated autophagic flux may thus be a new promising strategy against hepatic fibrosis. In this study, we synthesized four types of Nur77-based thiourea derivatives to determine their anti-hepatic fibrosis activity. Among the synthesized thiourea derivatives, 9e was the most potent inhibitor of hepatic stellate cells (HSCs) proliferation and activation. This compound could directly bind to Nur77 and inhibit TGF-β1-induced α-SMA and COLA1 expression in a Nur77-dependent manner. In vivo, 9e significantly reduced CCl 4 -mediated hepatic inflammation response and extracellular matrix (ECM) production, revealing that 9e is capable of blocking the progression of hepatic fibrosis. Mechanistically, 9e induced Nur77 expression and enhanced autophagic flux by inhibiting the mTORC1 signaling pathway in vitro and in vivo. Thus, the Nur77-targeted lead 9e may serve as a promising candidate for treatment of chronic liver fibrosis., 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 Inc. All rights reserved.)

Objectives: This study aims to investigate the high-risk factors for osteonecrosis of the femoral head (ONFH) after internal fixation with multiple cannulated compression screws for adult femoral neck fractures and to construct a prediction model., Patients and Methods: Between from January 2012 and December 2020, a total of 268 patients (138 males, 130 females; mean age: 53±10 years; range, 23 to 70 years) with ONFH who had complete follow-up data were included. Closed reduction in combination with open reduction were performed. All patients received internal fixation with multiple cannulated compression screws and were assigned to ONFH and non-ONFH groups. Logistic regression model was utilized to identify independent risk factors for postoperative ONFH, followed by constructing a nomogram prediction model. The predictive ability of the model was evaluated by receiver operating characteristic curve, Hosmer-Lemeshow test, and calibration curve., Results: Multivariate analysis revealed that older age (odds ratio [OR]: 2.307, 95% confidence interval [CI]: 1.295-4.108], Charlson Comorbidity Index (CCI) ≥2 (OR: 2.214, 95% CI: 1.035-4.739), fracture displacement (OR: 2.426, 95% CI: 1.122-5.247), unsatisfactory reduction (OR: 2.629, 95% CI: 1.275-5.423), postoperative removal of internal fixation implant (OR: 2.200, 95% CI: 1.051-4.604) were independent risk factors for postoperative ONFH (p<0.05). The nomogram prediction model constructed based on these clinical characteristics showed high predictive value (AUC=0.807) and consistency (p>0.05)., Conclusion: Age, comorbidity index, fracture type, reduction quality and postoperative removal of internal fixation implant are of utmost importance for postoperative ONFH in patients with femoral neck fractures. The established nomogram prediction model can accurately predict the occurrence of postoperative ONFH.

Rationale: Patients who have myasthenia gravis or dermatomyositis show clinical signs of muscular weakening. Ocular muscle involvement is uncommon, and symmetrical proximal limb weakness is the typical presentation of dermatomyositis. However, the earliest and most noticeable sign in those with myasthenia gravis is extraocular muscular paralysis. Dermatomyositis is frequently complicated by malignancy, and the common malignancies associated with dermatomyositis vary by region and ethnicity, while thymoma is relatively rare. About 10% to 15% of people with myasthenia gravis have thymoma, which is involved in the etiology of the disease., Patient Concerns: A 68-year-old female presented with ocular muscle weakness for 10 days that manifested as bilateral blepharoptosis with the phenomenon of "light in the morning and heavy in the evening." Imaging examination showed anterior mediastinal thymic tumor with metastasis., Diagnoses: After a thorough physical examination, we discovered bilateral upper limbs with grade IV muscle strength and the typical rash of dermatomyositis. In combination with elevated serum kinase levels and electromyography suggesting myogenic damage, the patient was finally diagnosed as dermatomyositis with multiple metastases of thymoma., Interventions: The patient received oral hydroxychloroquine sulfate, topical corticosteroids, and tacrolimus ointment, but these did not work very well. Subsequently, the patient underwent surgery combined with radiotherapy for the thymoma., Outcomes: Muscle weakness in the patient improved after effective treatment of tumor, and the rash mostly disappeared., Conclusion: Ocular muscle weakness and thymoma are more common in myasthenia gravis, but we cannot ignore the possibility of dermatomyositis. To further establish the diagnosis, a thorough physical examination and laboratory findings are required. Further tumor screening should be performed for patients with dermatomyositis. Early detection and management of possible tumors are essential to the treatment of dermatomyositis linked to malignancies., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The geochemistry of Li and Li isotopes is a promising tracer of chemical weathering processes for both modern and ancient times. Therefore, accurate and precise determination of the isotopic composition of Li is required for a large variety of complex geological samples with different Li concentrations and matrix/Li ratios. Especially, geochemical studies of precious geological samples with ultra-low lithium content and high matrix. In this study, the accuracy and the precision corresponding to Li isotopic measurements of low-level samples using multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) with membrane desolvation introduction system was evaluated. The method of MC-ICP-MS with membrane desolvation and a high-sensitivity X-skimmer cone, together with a simple one-step column separation enabled the high-precision isotopic analysis of Li quantities as small as 2 ng. The long-term instrumental external reproducibility of δ 7 Li values for the L-SVEC and SPEX-Li were 0.0 ± 0.1‰ ( n = 20) and 12.1 ± 0.4‰ ( n = 20), respectively. Based on the measurements on a series of international reference materials over the last two years. The measured δ 7 Li values for the standards with a variety of matrices, including BHVO-2, AGV-2 and seawater (NASS-6). The δ 7 Li values of BHVO-2 (4.58 ± 0.35‰), AGV-2 (6.85 ± 0.40‰) and NASS-6 (30.88 ± 0.20‰) are in agreement with the published data within the uncertainty. We also present analytical results for South China Sea surface seawater water, meteorite, limestones and rain water. These results demonstrate the validity of the method for obtaining highly precise and accurate outcomes., Competing Interests: 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., (This journal is © The Royal Society of Chemistry.)

Hepatic fibrosis remains a great challenge clinically. The orphan nuclear receptor Nur77 is recently suggested as the critical regulator of transforming growth factor-β (TGF-β) signaling, which plays a central role in multi-organic fibrosis. Herein, we optimized our previously reported Nur77-targeted compound 9 h for attempting to develop effective and safe anti-hepatic fibrosis agents. The critical pharmacophore scaffold of pyridine-carbonyl-hydrazine-1-carboxamide was retained, while the naphthalene ring was replaced with an aromatic ring containing pyridyl or indole groups. Four series of derivatives were thus generated, among which the compound 16f had excellent binding activity toward Nur77-LBD (K D  = 470 nM) with the best inhibitory activity against the TGF- β 1 activation of hepatic stellate cells (HSCs) and low cytotoxicity to normal mice liver AML-12 cells (IC 50  > 80 μM). In mice, 16f displayed potent activity against CCl 4 -induced liver fibrosis with improved liver function. Mechanistically, 16f-mediated inactivation of HSC and suppression of liver fibrosis were associated with its enhancement of autophagic flux in a Nur77-dependent manner. Together, 16f was identified as a potential anti-liver fibrosis agent. Our study suggests that Nur77 may serve as a critical anti-hepatic fibrosis target., 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. Published by Elsevier Inc.)

A cross-cultural comparison is made of delay discounting in samples of participants from Chile and China. Comparisons are made based on previous literature that suggests that individuals from an Asian culture should be willing to postpone delayed rewards more than are individuals from a Latin American culture. To test the cross-cultural validity of a hyperbolic discounting model, the model was fitted to both data sets. Additionally, a self-enhancement measure was evaluated as a potential mediator between culture of origin and delay discounting. Seventy-eight college students from China and 120 college students from Chile, with similar demographic backgrounds, discounted hypothetical monetary outcomes using an adjusting-amount titration procedure. Additionally, participants completed a self-enhancement measure. Age, academic major, gender, and grade point average were controlled. Chilean participants discounted much more steeply than Chinese nationals did. No support was obtained for the mediation of self-enhancement between culture of origin and degree of delay discounting. In both samples, delay discounting was better described by a hyperboloid than an exponential function, the only exception being the $10,000 condition in which the medians for Chilean participants' present subjective value were equally well explained by a hyperboloid and an exponential function., (© 2023 Society for the Experimental Analysis of Behavior.)

Lithium-sulfur batteries (LSBs) are some of the most promising energy storage systems to break the ceiling of Li-ion batteries. However, the notorious shuttle effect and slow redox kinetics give rise to low sulfur utilization and discharge capacity, poor rate performance, and fast capacity decay. It is proved that the reasonable design of the electrocatalyst is one of the important ways to improve the electrochemical performance of LSBs. Here, a core-shell structure with gradient adsorption capacity for reactants and sulfur products was designed. The Ni nanoparticles core coated with graphite carbon shell was prepared by one-step pyrolysis of Ni-MOF precursors. The design takes advantage of the principle that the adsorption capacity decreases from the core to the shell, and the Ni core with strong adsorption capacity is easy to attract and capture soluble lithium polysulfide (LiPS) during the discharge/charging process. This trapping mechanism prevents the diffusion of LiPSs to the outer shell and effectively inhibits the shuttle effect. In addition, the Ni nanoparticles within the porous carbon, as the active center, expose most of the inherent active sites to the surface area, thus achieving a rapid transformation of LiPSs, significantly reducing the reaction polarization, and improving the cyclic stability and reaction kinetics of LSB. Therefore, the S/Ni@PC composites exhibited excellent cycle stability (a capacity of 417.4 mA h g -1 for 500 cycles at 1C with a fading rate of 0.11%) and outstanding rate performance (1014.6 mA h g -1 at 2C). This study provides a promising design solution of Ni nanoparticles embedded in porous carbon for high-performance, safe and reliable LSB., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The Taiyuan Xishan Ecological Restoration Zone is located in the west of Taiyuan City and belongs to the Xishan Coalfield. Due to the resource development activity of coal mining, which is caused by coal gangue accumulation, surface vegetation degradation, bare surfaces, and other phenomena, it is most common in this area. These have an impact on the surface ecology; however, after ecological restoration, the surface ecology has been greatly improved. There are many extraction models of vegetation coverage based on pixel dichotomology combined with multispectral vegetation index, but we believe that the combination of visible light vegetation index to construct models is relatively unexplored. The main problem of how to use the RGB image data in order to quickly and accurately extract vegetation coverage information is still under investigation and needs researchers' attention. In this paper, through selecting the vegetation coverage as the evaluation index of ecological restoration effect, a new RGB vegetation coverage CIVE calculation model is innovatively proposed to solve the above problem, and on the basis of this model, the vegetation cover change analysis is carried out in the Xishan ecological restoration area of Taiyuan. According to the analysis of vegetation coverage change, relevant paper data, and the characteristics of multiple historical remote sensing images, the ecological restoration area of Taiyuan Xishan is divided into six typical areas. Through empirical evaluation, we summarize and analyze these six typical areas, which can provide typical demonstration roles for other ecological restoration areas. Our findings suggest that the proposed CIVE model realizes the extraction of vegetation cover information and long-term series dynamic monitoring of vegetation coverage.

Hypoxia reprograms cancer stem cells. Nur77, an orphan nuclear receptor, highly expresses and facilitates colorectal cancer (CRC) stemness and metastasis under a hypoxic microenvironment. However, safe and effective small molecules that target Nur77 for CSC depletion remain unexplored. Here, we report our identification of the ginsenoside compound K (CK) as a new ligand of Nur77. CK strongly inhibits hypoxia-induced CRC sphere formation and CSC phenotypes in a Nur77-dependent manner. Hypoxia induces an intriguing Nur77-Akt feed-forward loop, resulting in reinforced PI3K/Akt signaling that is druggable by targeting Nur77. CK directly binds and modulates Nur77 phosphorylation to block the Nur77-Akt activation loop by disassociating Nur77 from the p63-bound Dicer promoter. The transcription of Dicer that is silenced under a hypoxia microenvironment is thus reactivated by CK. Consequently, the expression and processing capability of microRNA let-7i-5p are significantly increased, which targets PIK3CA mRNA for decay. The in vivo results showed that CK suppresses cancer stemness and metastasis without causing significant adverse effects. Given that the majority of FDA-approved and currently clinically tested PI3K/Akt inhibitors are reversible ATP-competitive kinase antagonists, targeting Nur77 for PI3K/Akt inactivation may provide an alternative strategy to overcoming concerns about drug selectivity and safety. The mechanistic target identification provides a basis for exploring CK as a promising nutraceutical against CRC.

Hepatocellular carcinoma (HCC) commonly possesses chronical elevation of IRE1α-ASK1 signaling. Orphan nuclear receptor Nur77, a promising therapeutic target in various cancer types, is frequently silenced in HCC. In this study, we show that cryptomeridiol (Bkh126), a naturally occurring sesquiterpenoid derivative isolated from traditional Chinese medicine Magnolia officinalis , has therapeutic efficacy in HCC by aggravating the pre-activated UPR and activating the silenced Nur77. Mechanistically, Nur77 is induced to sense IRE1α-ASK1-JNK signaling and translocate to the mitochondria, which leads to the loss of mitochondrial membrane potential (Δψm). The Bkh126-induced aggravation of ER stress and mitochondrial dysfunction result in increased cytotoxic product of reactive oxygen species (ROS). The in vivo anti-HCC activity of Bkh126 is superior to that of sorafenib, currently used to treat advanced HCC. Our study shows that Bkh126 induces Nur77 to connect ER stress to mitochondria-mediated cell killing. The identification of Nur77 as a molecular target of Bhk126 provides a basis for improving the leads for the further development of anti-HCC drugs.

Purpose: Early detection and prognostic prediction of hepatocellular carcinoma (HCC) remain a great challenge. In this study, we explored the role and diagnostic significance of stanniocalcin 2 (STC2), recently identified as a secretory protein, in HCC., Methods: STC2 mRNA and protein in HCC tissues were examined by qRT-PCR and immunohistochemistry. The regulatory role of HCC growth by STC2 was evaluated in vitro and in vivo. Serum STC2 levels were determined in HCC patients and compared to those with liver cirrhosis (LC) and normal controls (NC). The difference and significance of STC2 levels between groups were analyzed by Mann-Whitney U -test. The diagnostic value of serum STC2 in detecting early HCC was assayed with receiver operating characteristics (ROC). The association of STC2 with overall survival (OS) was determined with Kaplan-Meier method., Results: STC2 was elevated in about 77.1% HCC patients and correlated with advanced tumor progression. Overexpression or knockdown of STC2 stimulated or suppressed HCC colony formation and xenograft tumor growth. AKT activation played a critical role in tumor-promoting effect of STC2. The median level of serum STC2 in HCC patients (n = 98, 2086.6 ng/L) was 2.6-fold and 4.2-fold that in LC patients (n = 42, 801.9 ng/L) and NC (n = 26, 496.9 ng/L), respectively. A cut-off value 1493 ng/L for STC2 could distinguish early HCC from LC with a sensitivity of 76.9% and a specificity of 76.2%, both of which were superior to AFP at 20 μg/L (sensitivity 69.2%, specificity 52.4%). STC2 was positive in 77.8% (14/18) AFP-negative patients. High STC2 level was correlated with poor overall and disease specific survival., Conclusion: STC2 is upregulated in both tumor and serum of HCC patients, and its overexpression promotes HCC via AKT pathway. STC2 possesses a diagnostic significance and may serve as an auxiliary biomarker of AFP for detecting early HCC., Competing Interests: The authors have declared no conflicts of interest for this work., (© 2022 Wu et al.)

Current wound healing models generally employ full-thickness or irregular split wounds. Consequently, assessing the type of healing at varying wound depths and determining the deepest level at which wounds can regenerate has been a challenge. We describe a wound model that allows assessment of the healing process over a continuous gradient of wound depth, from epidermal to full-thickness dermal loss. Further, we investigate whether green fluorescent protein-labeled bone marrow mesenchymal stem cells (BM-MSCs/GFP) transplantation could regenerate deeper wounds that might otherwise lead to scar formation. A wound gradient was created on the back of 120 Sprague Dawley rats, which were randomized into the BM-MSCs/GFP and control group. These were further subdivided into 6 groups where terminal biopsies of the healing wounds were taken at days 1, 3, 5, 7, 14, and 21 post-operatively. At each observed time point, the experimental animals were anesthetized and photographed, and depending on the group, the animals euthanized and skin taken for rapid freezing, haemotoxylin and eosin staining, and vascular endothelial growth factor (VEGF) immunohistochemistry. We found the deepest layer to regenerate in the control group was at the level of the infundibulum apex, while in the BM-MSCs/GFP group this was deeper, at the opening site of sebaceous duct at hair follicle in which had the appearance of normal skin and less wound contraction than the control group ( P value less than .05). The expression of VEGF in BM-MSCs/GFP group was higher than that in control group ( P value less than .05). The number of vessels increased from 2.5 ± 0.2/phf of control group to 5.0 ± 0.3/phf of BM-MSCs/GFP ( P value less than .05). The progressively deepening wound model we described can identify the type of wound repair at increasing depths. Further, topical transplantation of BM-MSCs/GFP significantly improved regeneration of deeper wounds from infundibulum apex (maximum depth of control group regeneration) to the opening site of sebaceous duct at hair follicle level., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2020 The Author(s).)

Objective: The aims of this study were to characterize the evolution of routine blood values within the first 10 days of illness and coronary artery outcome in infants < 8 months with Kawasaki disease (KD) and to identify risk factors for coronary artery aneurysm (CAA)., Methods: Laboratory data, clinical features and coronary artery outcomes from 78 infants < 8 months old and 86 patients between 8 months and 7 years old were retrospectively analyzed. Logistic regression analysis was conducted to evaluate the potential risk factors for CAA., Results: Infants < 8 months old were more likely to present with incomplete KD (37.2% vs 4.7%, P < 0.001), erythema and induration at the BCG inoculation site (24.4% vs 3.5%, P < 0.001) and CAA (47.4% vs 15.1%, P < 0.001) even with timely diagnosis and treatment with intravenous immunoglobulin (IVIG) compared with patients ≥8 months old. Clinical feature related to diagnostic criteria for KD including bilateral conjunctival injection, oral changes, unilateral cervical lymphadenopathy and extremity changes were less common in the younger group. During the acute phase, the percentage neutrophils and neutrophil to lymphocyte ratio [NLR] peaked on median illness day 3, followed by white blood cell (WBC) and CRP on median illness day 4, hemoglobin on median illness day 7 and platelet count on median illness day 9. CAA occurred on median illness day 6 and regressed on median illness day 28. Multivariate logistic regression analysis revealed that the peak percentage neutrophils (odds ratio [OR] per 0.1: 1.597, 95% confidence interval [CI]: 1.041-2.452, P = 0.032) and the peak platelet count (OR per 10 × 10 9 /L: 1.029, 95% CI: 1.004-1.055, P = 0.024) were independent risk factors for CAA. Hemoglobin on the 5th day was associated with persistent CAA at 1 year after KD onset., Conclusion: Factors associated with CAA include a high peak percentage neutrophils, increased peak platelet count, and reduced hemoglobin within 4-6 days during the acute phase of KD. Therefore, this population should receive primary therapy with IVIG and adjunctive anti-inflammatory medications., (© 2021. The Author(s).)

The aging of the immune system is not only an inevitable result but also an important cause of physical aging. The aging of the immune system is rooted in the aging of hematopoietic cells (HSCs), which manifests as decreasing functionality of the adaptive immune system and the innate immune system. C57BL/6 mice of different ages were collected in this study to better understand the changes in the structures of the innate and adaptive immune systems in individuals of different ages and the distribution and changes in immune cells with stem cell properties. The immune cells of the innate and adaptive immune systems, including DCs, monocytes, macrophages, CD4 + T lymphocytes, CD8 + T lymphocytes, and B lymphocytes, were assessed, and the proportions of cells with stem cell properties among these immune cell populations were also tested. Overall, immune cells in the peripheral blood, spleen, and bone marrow of mice exhibit certain regular properties with increasing age. The trend of changes in immune cells in different immune organs differs with age. The changes in lymphocytes in the peripheral blood are more sensitive. Their proportions increase slowly with age and then decrease rapidly to a very low level (less than 5%) after a certain point (9 or 13 months old). Nine to 13 months of age is the most critical time point for assessing changes in the immune system of mice and the most critical time point for detecting changes in the proportion of stem cells. After 13 months of age, the balance and stability of stem cells in mice are disrupted, and animals begin to age rapidly. The ratio of Ly6A to E + CD117 + cells in the peripheral blood, particularly lymphocytes involved in adaptive immunity, represents a specific marker for predicting immune senescence and body senescence., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objectives: Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) plays a critical role in the success of lumbar spinal fusion with autogenous bone graft. This study aims to explore the role and specific mechanism of miR-34c-5p in osteogenic differentiation of BMSCs., Methods and Results: Rabbit model of lumbar fusion was established by surgery. The osteogenic differentiation dataset of mesenchymal stem cells was obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed miRNAs were analyzed using R language (limma package). The expressions of miR-34c-5p, miR-199a-5p, miR-324-5p, miR-361-5p, RUNX2, OCN and Bcl-2 were determined by qRT-PCR and Western blot. ELISA, Alizarin red staining and CCK-8 were used to detect the ALP content, calcium deposition and proliferation of BMSCs. The targeted binding sites between miR-34c-5p and Bcl-2 were predicted by the Target database and verified using dual-luciferase reporter assay. MiR-34c-5p expression was higher in rabbit lumbar fusion model and differentiated BMSCs than normal rabbit or BMSCs. The content of ALP and the deposition of calcium increased with the osteogenic differentiation of BMSCs. Upregulation of miR-34c-5p reduced cell proliferation and promoted ALP content, calcium deposition, RUNX2 and OCN expression compared with the control group. The effects of miR-34c-5p inhibitor were the opposite. In addition, miR-34c-5p negatively correlated with Bcl-2. Upregulation of Bcl-2 reversed the effects of miR-34c-5p on ALP content, calcium deposition, and the expressions of RUNX2 and OCN., Conclusions: miR-34c-5p could promote osteogenic differentiation and suppress proliferation of BMSCs by inhibiting Bcl-2.

Mangostin, which has the function of anti-inflammatory, antioxidant, and anticancer, etc, is one of the main active ingredients of the hull of the mangosteen. The main objective of the study was to elucidate its anti-cancer function and possible mechanism. α-Mangostin was separated and structurally confirmed. MTT method was used to check the effect of mangostin on breast cancer cell proliferation. Then the effect of α-Mangostin on the transcriptional activity of RXRα was tested by dual-luciferase reporter gene assay. And Western blot (WB) was used to detect the expression of apoptosis-related proteins or cell cycle-associated proteins after treatment. Also, this study was to observe the effects of α-Mangostin on the invasion of breast cancer cell line MDA-MB-231. α-Mangostin regulates the downstream effectors of the PI3K/AKT signaling pathway by degrading RXRα/tRXRα. α-Mangostin can trigger PARP cleavage and induce apoptosis, which may be related to the induction of upregulated BAX expression and downregulation of BAD and cleaved caspase-3 expression in MDA-MB-231 cells through blockade of AKT signaling. The experiments verify that α-Mangostin have evident inhibition effects of invasion and metastasis of MDA-MB-231 cells. Cyclin D1 was involved in the anticancer effects of α-Mangostin on the cell cycle in MDA-MB-231 cells. α-Mangostin induces apoptosis, suppresses the migration and invasion of breast cancer cells through the PI3K/AKT signaling pathway by targeting RXRα, and cyclin D1 has involved in this process., 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 © 2021 Zhu, Li, Ning, Yuan, Zhong, Wu, Zeng.)

Non-small cell lung cancer (NSCLC), a commonly diagnosed lung cancer, is characterized by a high incidence of metastatic spread to the brain, which adversely impacts prognosis. The present study aimed to assess the value of combined dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) in predicting the treatment outcomes of whole-brain radiotherapy (WBRT) and gefitinib in brain metastases from non-small cell lung cancer (NSCLC) from the perspectives of response rate and short- and long-term efficacy. These results suggested that the indicators measured by DCE-MRI combined with DWI can be used as key imaging-derived markers that predicted the efficacy of WBRT combined with gefitinib in NSCLC patients with brain metastases. Specifically, patients with higher ΔADC mid and ΔADC post values showed better treatment outcomes. ROC curve analysis indicated ADC post , ΔADC post , ΔADC post (%), and tumor regression rate as the best predictors of efficacy of WBRT combined with gefitinib in these patients. The short-term and long-term effects noted were also significant. Taken together, the findings of this study reveal that tumor regression rate, ADC post , ΔADC post , and ΔADC post (%) can be used as important imaging indicators that predict the therapeutic effect of WBRT combined with gefitinib in NSCLC patients with brain metastases., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2021 Chengyu Ye et al., published by De Gruyter.)

The incidence of type 2 diabetes (T2D) is increasing at an alarming rate worldwide. Bariatric surgical procedures, such as the vertical sleeve gastrectomy and Roux-en-Y gastric bypass, are the most efficient approaches to obtain substantial and durable remission of T2D. The benefits of bariatric surgery are realized through the consequent increased satiety and alterations in gastrointestinal hormones, bile acids, and the intestinal microbiota. A comprehensive understanding of the mechanisms by which various bariatric surgical procedures exert their benefits on T2D could contribute to the design of better non-surgical treatments for T2D. In this review, we describe the classification and evolution of bariatric surgery and explore the multiple mechanisms underlying the effect of bariatric surgery on insulin resistance. Based upon our summarization of the current knowledge on the underlying mechanisms, we speculate that the gut might act as a new target for improving T2D. Our ultimate goal with this review is to provide a better understanding of T2D pathophysiology in order to support development of T2D treatments that are less invasive and more scalable., Competing Interests: Conflict-of-interest statement: The authors declare having no conflict of interests for this article., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

We previously reported 5-((8-methoxy-2-methylquinolin-4-yl)amino)-1H-indole- 2-carbohydrazide derivatives as new Nur77 modulators. In this study, we explored whether the 8-methoxy-2-methylquinoline moiety and bicyclic aromatic rings at the N'-methylene position were critical for their antitumor activity against hepatocellular carcinoma (HCC). For this purpose, a small library of 5-substituted 1H-indole-2-carbohydrazide derivatives was designed and synthesized. We found that the 8-methoxy-2-methylquinoline moiety was a fundamental structure for its biological function, while the introduction of the bicyclic aromatic ring into the N'-methylene greatly improved its anti-tumor effect. We found that the representative compound 10E had a high affinity to Nur77. The K D values were in the low micromolar (2.25-4.10 μM), which were coincident with its IC 50 values against the tumor cell lines (IC 50  < 3.78 μM). Compound 10E could induce autophagic cell death of liver cancer cells by targeting Nur77 to mitochondria while knocking down Nur77 greatly impaired anti-tumor effect. These findings provide an insight into the structure-activity relation of Quinoline-Indole-Schiff base derivatives and further demonstrate that antitumor agents targeting Nur77 may be considered as a promising strategy for HCC therapy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The large-scale and controllable synthesis of novel N-doped three-dimensional (3D) carbon nanocage-decorated carbon skeleton sponges (Co-NCMS) is introduced. These Co-NCMS were highly active and durable non-noble metal catalysts for the oxygen reduction reaction (ORR). This hybrid electrocatalyst showed high ORR activity with a diffusion-limiting current of 5.237 mA·cm -2 in 0.1 M KOH solution through the highly efficient 4e - pathway, which was superior to that of the Pt/C catalyst (4.99 mA·cm -2 ), and the ORR Tafel slope is ca. 67.7 mV·dec -1 at a high potential region, close to that of Pt/C. Furthermore, Co-NCMS exhibited good ORR activity in acidic media with an onset potential comparable to that of the Pt/C catalyst. Most importantly, the prepared catalyst showed much higher stability and better methanol tolerance in both alkaline and acidic solutions. The power density obtained in a proton exchange membrane fuel cell was as high as 0.37 W·cm -2 at 0.19 V compared with 0.45 W·cm -2 at 0.56 V for the Pt/C catalyst. In Co-NCMS, the N-doped carbon nanocages facilitated the diffusion of the reactant, maximizing the exposure of active sites on the surface and protecting the active metallic core from oxidation. This made Co-NCMS one of the best non-noble metal catalysts and potentially offers an alternative approach for the efficient utilization of active transition metals in electrocatalyst applications., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Background: Glioma is the most common primary intracranial tumor and is associated with poor prognosis. Identifying effective biomarkers for glioma is particularly important. MXRA5, a secreted glycoprotein, is involved in cell adhesion and extracellular matrix remodeling and has been reported to be expressed in many cancers. However, the role and mechanism of action of MXRA5 in gliomas remain unclear. This study was aimed at investigating the role of MXRA5 at the transcriptome level and its clinical prognostic value., Methods: In this study, RNA microarray data of 301 glioma patients from the Chinese Glioma Genome Atlas (CGGA) were collected as a training cohort and RNA-seq data of 702 glioma samples from The Cancer Genome Atlas (TCGA) were used for validation. We analyzed the clinical and molecular characteristics as well as the prognostic value of MXRA5 in glioma. In addition, the expression level of MXRA was evaluated in 28 glioma tissue samples., Results: We found that MXRA5 expression was significantly upregulated in high-grade gliomas and IDH wild-type gliomas compared to controls. Receiver operating characteristic (ROC) analysis showed that MXRA5 is a potential marker of the mesenchymal subtype of glioblastoma multiforme (GBM). We found that MXRA5 expression is highly correlated with immune checkpoint molecule expression levels and tumor-associated macrophage infiltration. High MXRA5 expression could be used as an independent indicator of poor prognosis in glioma patients., Conclusion: Our study suggests that MXRA5 expression is associated with the clinicopathologic features and poor prognosis of gliomas. MXRA5 may play an important role in the immunosuppressive microenvironment of glioma. As a secreted glycoprotein, MXRA5 is a potential circulating biomarker for glioma, deserving further investigation., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 Jin-Zhang Sun et al.)

The transcription factor NF-YB (nuclear factor-YB) family is a subfamily of the nuclear factor Y (NF-Y), which plays an important role in regulating plant growth, development and participates in various stress responses. Although the NF-Y family has been studied in many species, it is still obscure in Eucalyptus grandis . In this study, 23 EgNF-YB genes in eucalyptus were identified and unevenly distributed on 11 chromosomes. Phylogenetic analysis showed the EgNF-YB genes were divided into two clades, LEC-1 type and non-LEC1 type. The evolution of distinct clades was relatively conservative, the gene structures were analogous, and the differences of genetic structures among clades were small. The expression profiles showed that the distinct EgNF-YB genes were highly expressed in diverse tissues, and EgNF-YB4/6/13/19/23 functioned in response to salinity, heat and cold stresses. Our study characterized the phylogenetic relationship, gene structures and expression patterns of EgNF-YB gene family and investigated their potential roles in abiotic stress responses, which provides solid foundations for further functional analysis of NF-YB genes in eucalyptus.

Background: Colorectal cancer (CRC) and the associated metastatic lesions are reported to be hypoxic. Hypoxia is a common feature in the tumor microenvironment and a potent stimulant of CRC. We have identified a regulatory role of Nur77 on Akt activation to enhance β-catenin signaling essential for CRC progression under hypoxic conditions. Methods: The functional role of Nur77 in hypoxia-induced EMT was examined by scattering assays to monitor the morphologies of CRC cell lines under 1% O 2 . Sphere formation assays were performed to investigate whether Nur77 induced cancer stem cell-like properties in hypoxic CRC cells. The expression of various epithelial-to-mesenchymal transition (EMT) and stemness markers was analyzed by qPCR and Western blotting. Finally, Nur77 function and signaling in vivo was ascertained in subcutaneous tumor xenograft or liver metastasis model in nude mice using CRC cells stably transfected with appropriate constructs. Results: Herein, we show, for the first time, that Nur77 is a novel regulator of microRNA biogenesis that may underlie its significant tumor-promoting activities in CRC cells under hypoxia. Mechanistically, Nur77 interacted with the tumor suppressor protein p63, leading to the inhibition of p63-dependent transcription of Dicer, an important miRNA processor and subsequent decrease in the biogenesis of let-7i-5p which targeted the 3'UTR of p110α mRNA and regulated its stability. Knockdown of Nur77 or overexpression of let-7i-5p inhibited the tumor metastasis in vivo . Conclusion: Our data uncovered a novel mechanistic link connecting Nur77, Akt, and invasive properties of CRC in the hypoxic microenvironment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

A bound state between a quantum emitter (QE) and surface plasmon polaritons (SPPs) can be formed, where the excited QE will not relax completely to its ground state and is partially stabilized in its excited state after a long time. We develop some theoretical methods for investigating this problem and show how to form such a bound state and its effect on the non-Markovian decay dynamics. We put forward an efficient numerical approach for calculating the analytical part of the self-energy for frequency below the lower energy threshold. We also propose an efficient formalism for obtaining the long-time value of the excited-state population without calculating the eigenfrequency of the bound state or performing a time evolution of the system, in which the probability amplitude for the excited state in the steady limit is equal to one minus the integral of the evolution spectrum over the positive frequency range. With the above two quantities obtained, we show that the non-Markovian decay dynamics of an initially excited QE can be efficiently obtained by the method based on the Green's function expression for the evolution operator when a bound state exists. A general criterion for identifying the existence of a bound state is presented. The performances of the above methods are numerically demonstrated for a QE located around a metal nanosphere and in a gap plasmonic nanocavity. Numerical results show that these methods work well and the QE becomes partially stabilized in its excited state at a long time for the transition dipole moment beyond its critical value. In addition, it is also found that this critical value is heavily dependent on the distance between the QE and the metal surface, but nearly independent on the size of the nanosphere or the rod. Our methods can be utilized to understand the suppressed decay dynamics for a QE in an open quantum system and provide a general picture on how to form such a bound state.

Objective: The aim of this study was to update the epidemic situation of dengue fever (DF) and provide new insights for the consideration of disease control in Fujian province, China., Methods: Details about DF cases in Fujian reported during 2004-2017 were collected and analyzed. The envelope (E) genes of isolates of dengue virus (DENV) were sequenced for phylogenetic analysis., Results: The number of imported DF cases had increased dramatically since 2013, and the source regions expanded from Southeast Asia to South Asia, America, Oceania, and Africa, as well as the surrounding provinces. This resulted in local outbreaks and indigenous cases of DF that occurred more frequently, with 10 of 13 local outbreaks and 85.9% (1,252/1,458) of indigenous cases reported in 2013-2017. Compared with only two coastal cities before 2013, four coastal and one inland city in 2013-2017 experienced the local DF outbreaks. The phylogenetic analysis of E genes confirmed that the import of DENV, not only from abroad but also from the surrounding provinces, played an important role in dissemination and local outbreaks of DF in Fujian., Conclusions: The frequent import of DF cases from not only abroad but also the surrounding provinces resulted in increased incidence, frequent local outbreaks, and expansion of distribution in Fujian in recent years. There is a need for urgent measures to improve disease control in this province., (Copyright © 2020 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Rationale : Glycogen synthase kinase-3β (GSK-3β) plays key roles in metabolism and many cellular processes. It was recently demonstrated that overexpression of GSK-3β can confer tumor growth. However, the expression and function of GSK-3β in hepatocellular carcinoma (HCC) remain largely unexplored. This study is aimed at investigating the role and therapeutic target value of GSK-3β in HCC. Methods : We firstly clarified the expression of GSK-3β in human HCC samples. Given that deviated retinoid signalling is critical for HCC development, we studied whether GSK-3β could be involved in the regulation. Since sorafenib is currently used to treat HCC, the involvement of GSK-3β in sorafenib treatment response was determined. Co-immunoprecipitation, GST pull down, in vitro kinase assay, luciferase reporter and chromatin immunoprecipitation were used to explore the molecular mechanism. The biological readouts were examined with MTT, flow cytometry and animal experiments. Results : We demonstrated that GSK-3β is highly expressed in HCC and associated with shorter overall survival (OS). Overexpression of GSK-3β confers HCC cell colony formation and xenograft tumor growth. Tumor-associated GSK-3β is correlated with reduced expression of retinoic acid receptor-β (RARβ), which is caused by GSK-3β-mediated phosphorylation and heterodimerization abrogation of retinoid X receptor (RXRα) with RARα on RARβ promoter. Overexpression of functional GSK-3β impairs retinoid response and represses sorafenib anti-HCC effect. Inactivation of GSK-3β by tideglusib can potentiate 9- cis -RA enhancement of sorafenib sensitivity (tumor inhibition from 48.3% to 93.4%). Efficient induction of RARβ by tideglusib/9- cis- RA is required for enhanced therapeutic outcome of sorafenib, which effect is greatly inhibited by knocking down RARβ. Conclusions : Our findings demonstrate that GSK-3β is a disruptor of retinoid signalling and a new resistant factor of sorafenib in HCC. Targeting GSK-3β may be a promising strategy for HCC treatment in clinic., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Ginseng is a group of cosmopolitan plants with more than a dozen species belonging to the genus Panax in the family Araliaceae that has a long history of use in traditional Chinese medicine (TCM). Among the bioactive constituents extracted from ginseng, ginseng saponins are a group of natural steroid glycosides and triterpene saponins found exclusively throughout the plant. Studies have shown that these ginseng saponins play a significant role in exerting multiple therapeutic effects. This review covers their chemical structure and classification, as well as their pharmacological activities, including their regulatory effects on immunomodulation, their anticancer effects, and their functions in the central nervous and cardiovascular systems. The general benefits of ginseng saponins for boosting physical vitality and improving quality of life are also discussed. The review concludes with fruitful directions for future research in the use of ginseng saponins as effective therapeutic agents.

Organ-specific colonization suggests that specific cell-cell recognition is essential. Yet, very little is known about this particular interaction. Moreover, tumor cell lodgement requires binding under shear stress, but not static, conditions. Here, we successfully isolate the metastatic populations of cancer stem/tumor-initiating cells (M-CSCs). We show that the M-CSCs tether more and roll slower than the non-metastatic (NM)-CSCs, thus resulting in the preferential binding to the peritoneal mesothelium under ascitic fluid shear stress. Mechanistically, this interaction is mediated by P-selectin expressed by the peritoneal mesothelium. Insulin-like growth factor receptor-1 carrying an uncommon non-sulfated sialyl-Lewis x (sLe x ) epitope serves as a distinct P-selectin binding determinant. Several glycosyltransferases, particularly α1,3-fucosyltransferase with rate-limiting activity for sLe x synthesis, are highly expressed in M-CSCs. Tumor xenografts and clinical samples corroborate the relevance of these findings. These data advance our understanding on the molecular regulation of peritoneal metastasis and support the therapeutic potential of targeting the sLe x -P-selectin cascade.

Due to both the hidden nature and the irreversibility of Alzheimers disease (AD), it has become the killer of the elderly and is thus the focus of much attention in the medical field. Radiologists compare the predicted brain age with the ground truth in order to provide a preliminary analysis of AD, which helps doctors diagnose AD as early in its development as possible. In this paper, a transfer learning-based method of predicting brain age using MR images and dataset of a public brain was proposed. In order to get the best transfer results, we froze different layers and only fine-tuned the remaining layers. We used three planes of brain MR images together to predict age for the first time and experiment results showed that the proposed method performs better than the state-of-the-art method under mean absolute error metric by 0.6 years. In addition, to explore the relationship between brain MR images of different planes and predicted age accuracy, we used three different planes of brain MR images to predict age respectively for the first time and found that sagittal plane MR images outperformed two other planes in age estimation. Finally, our research identified, the effective regions that contribute to brain age estimation for cognitively normal individuals and for AD patients with deep learning. For AD patients, the effective region is mainly concentrated in the frontal lobe of the brain, verifying the relevant medical conclusions about AD.

Objective: In this work, the relationship between octamer binding transcription factor 4 (OCT-4) expression and the clinicopathological features of cervical cancer (CC) is evaluated in detail. Methods: The library databases Pubmed, Embase, Cochrane library, Wan Fang and Chinese National Knowledge Infrastructure (CNKI) were searched for research related to these concepts published from the time the databases were established until May 2018. The obtained studies are screened, extracted, and evaluated according to the inclusion and exclusion criteria, and meta-analysis is carried out via RevMan 5.3. Results: Ten case-control studies, including 408 cases of CC, 164 cases of cervical intraepithelial neoplasia (CIN), and 148 cases of normal cervix, are included in the analysis. Results show that OCT-4 levels are statistically significantly different between the CC and normal cervical tissue groups (odds ratio (OR) = 15.59, 95% confidence interval (CI): 8.70, 27.94), the CC and CIN groups (OR = 5.64, 95% CI: 3.23, 9.86), the CIN and normal cervical tissues groups (OR = 7.13, 95% CI: 2.41, 21.05), and the CC well/moderately differentiated and poorly differentiated groups (OR = 0.44, 95% CI: 0.24, 0.81). OCT-4 is not statistically significantly different between CIN I + II and CIN III tissues (OR = 0.40, 95% CI: -0.02, 0.81), the CC lymphatic and non-lymphatic metastasis groups (OR = 1.93, 95% CI: 0.83, 4.47), the FIGO I and FIGO II groups (OR = 0.79, 95% CI: 0.29, 2.13), and the adenocarcinoma and squamous cell carcinoma groups (OR = 1.55, 95% CI: 0.70, 3.44). Conclusions: The available evidence suggests that OCT-4 expression is associated with CC malignancy and histological differentiation. This finding, however, is subject to quantitative studies and quality tests., (© 2019 The Author(s).)

Objective- The topographical distribution of atherosclerosis in vasculature underscores the importance of shear stress in regulating endothelium. With a systems approach integrating sequencing data, the current study aims to explore the link between shear stress-regulated master transcription factor and its regulation of endothelial cell (EC) function via epigenetic modifications. Approach and Results- H3K27ac (acetylation of histone 3 lysine 27)-ChIP-seq (chromatin immunoprecipitation followed by high throughput sequencing), ATAC-seq (an assay for transposase-accessible chromatin-sequencing), and RNA-seq (RNA-sequencing) were performed to investigate the genome-wide epigenetic regulations in ECs in response to atheroprotective pulsatile shear stress (PS). In silico prediction revealed that KLF4 binding motifs were enriched in the PS-enhanced H3K27ac regions. By integrating PS- and KLF4-modulated H3K27ac, we identified 18 novel PS-upregulated genes. The promoter regions of these genes showed an overlap between the KLF4-enhanced assay for transposase-accessible chromatin signals and the PS-induced H3K27ac peaks. Experiments using ECs isolated from mouse aorta, lung ECs from EC-KLF4-TG versus EC-KLF4-KO mice, and atorvastatin-treated ECs showed that ITPR3 (inositol 1,4,5-trisphosphate receptor 3) was robustly activated by KLF4 and statins. KLF4 ATAC-qPCR (quantitative polymerase chain reaction) and ChIP-qPCR further demonstrated that a specific locus in the promoter region of the ITPR3 gene was essential for KLF4 binding, H3K27ac enrichment, chromatin accessibility, RNA polymerase II recruitment, and ITPR3 transcriptional activation. Deletion of this KLF4 binding locus in ECs by using CRISPR-Cas9 resulted in blunted calcium influx, reduced expression of endothelial nitric oxide synthase, and diminished nitric oxide bioavailability. Conclusions- These results from a novel multiomics study suggest that KLF4 is crucial for PS-modulated H3K27ac that allow the transcriptional activation of ITPR3. This novel mechanism contributes to the Ca 2+ -dependent eNOS (endothelial nitric oxide synthase) activation and EC homeostasis.

Human dental pulp stem cells (hDPSCs) are primarily derived from the pulp tissues of permanent third molar teeth. They were widely used in human bone tissue engineering. It was previously indicated that microRNA (miR) expressions are closely associated with hDPSCs development. However, the specific effect of miR-488 on hDPSCs still remains unclear. In this study, we aimed to investigate effects of miR-488 on the differentiation of hDPSCs into odontoblast cells through the p38 mitogen-activated protein kinases (MAPK) signaling pathway by binding to MAPK1. The hDPSCs were isolated and cultured in vitro. Dual-luciferase reporter gene assay was performed to test the relationship between MAPK1 (p38) and miR-488. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to detect the mRNA and protein expressions of p38 MAPK signaling pathway-related genes (MAPK1, Ras, and Mitogen-activated protein kinase kinase 3/6 [MKK3/6]), along with expressions of dentin Sialophosphoprotein (DSPP), alkaline phosphatase (ALP), and osteonectin (OCN). ALP staining and alizarin red staining were conducted to detect ALP activity and degree of mineralization. Initially, we found that MAPK1 was the target gene of miR-488. Besides, downregulation of miR-488 was observed to stimulate the p38 MAPK signaling pathway and to increase the messenger RNA and protein expressions of DSPP, ALP, and OCN. Furthermore, ALP activity and formation of a mineralized nodule in hDPSCs were enhanced upon downregulation of miR-488. The aforementioned findings provided evidence supporting that downregulation of miR-488 promotes odontoblastic differentiation of hDPSCs through the p38 MAPK signaling pathway by targeting MAPK1, paving the basis for further study about hDPSCs., (© 2018 Wiley Periodicals, Inc.)

Retinoic acid receptors (RARs) are ligand-dependent transcription factors of nuclear hormone receptor superfamily (NR). They are important pharmacological targets and current drug development paradigms are largely based on their nuclear transcription mechanism (genomic action). However, the side effects and limited therapeutic efficacy of retinoid-like drugs with such strategy remain a problem in clinical practice. Increasing evidences have demonstrated that many NRs including RARs can act outside the nucleus in a transcription-independent manner (non-genomic action), which are often implicated in human pathological conditions, suggesting that targeting to the non-genomic signaling of NRs is an alternative method for drug discovery. We recently reported that acacetin could antagonize the non-genomic action of RARγ via tipping the balance of AKT-p53 driven by RARγ from tumor promoting to tumor suppressive effect. This chapter provides methodology for identification of acacetin as a ligand and regulator of non-genomic signaling of RARγ. These laboratory protocols should be helpful for those researchers and beginners who are passionate about identifying chemical leads to probe the non-genomic roles of RARs and other NRs for developing new therapeutic technologies.

In many individuals with renal cell carcinoma (RCC), a hereditary cause may have contributed to cancer development. Various risk factors can be suggestive of a genetic contribution, including early disease onset, multifocal or bilateral tumors, family history of RCC, and personal/family history of other benign or malignant tumors. Genetic counseling and understanding of the entire family tree are the first steps in evaluation and will determine if the patient should proceed with testing. Methods of testing have changed to next-generation sequencing, which allows multiple genes to be evaluated together. The results of testing have significant implications for the individual and his or her family members. Screening of the kidney and at-risk organs ensues, with most algorithms focused on early diagnosis and intervention to limit morbidity and mortality of disease manifestations. A comprehensive clinical program that can offer multidisciplinary care is useful for several complex cancer syndromes. Management of localized and advanced hereditary kidney cancers may differ from the sporadic forms of RCC. Knowledge of the genetics can have significant management implications and if necessary genetic evaluation can be expedited to allow treatment decisions.

Objective: To evaluate the effect and cost-effectiveness of three commonly used molluscicides, 4% "Luo-wei" (tea-seed distilled saponins, TDS), 50% niclosamide ethanolamine salt wettable powder (NESWP), and 26% metaldehyde and niclosamide suspension concentrate (MNSC) in large-scale field application, so as to provide the references for formulating the strategy of snail control., Methods: The field test and parallel comparison were implemented. A marshland with Oncomelania hupensis snails of the Yangtze River was divided into 4 parts (10 hm 2 ) for the research, and three of them were experimental areas while the last one was a blank control area. The experimental areas were sprayed with 4% "Luo-wei", 50% NESWP and 26% MNSC respectively for 3 times and the interval was 1 week. Seven days after each spraying the effect of snail control was investigated, and the costs of molluscicides, labor, transportation, fuel consumption and mechanical loss were recorded. The cost of each molluscicide, snail mortality, snail density, and the cost of increasing 1% of snail mortality per 100 m 2 were analyzed and compared., Results: After the first, second and third spraying, the corrected snail mortality rates were 67.34%, 76.55% and 84.60% respectively in the 4% "Luo-wei" group; the corrected snail mortality rates were 64.71%, 75.17% and 83.89% respectively in the 50% NESWP group; the corrected snail mortality rates were 66.55%, 76.27% and 86.67% respectively in the 26% MNSC group. There was no significant difference among the 3 groups in the snail mortality at the same spraying time (χ 2 = 1.590, 0.571, 3.238, all P > 0.05) . In addition, along with the increase of the spraying times, the snail mortality of each group was increased significantly compared to that of the control group (χ 2 = 79.333, 94.718, 117.020, all P < 0.01) . After the first, second and third spraying, the reduction rates of snail density were 69.82%-86.60% in the 4% "Luo-wei" group, 68.66%-86.55% in the 50% NESWP group, and 71.89%-88.87% in the 26% MNSC group respectively. The decreasing amplitude of the snail density was more than 85% in all the experimental areas after 3 rounds of spraying molluscicide. The snail control costs per 100 hm 2 were 19.57, 11.97 Yuan and 10.47 Yuan in the 4% "Luo-wei" group, 50% NESWP group, and 26% MNSC group respectively. After the first, second and third spraying, the costs of increasing 1% of snail mortality per 100 m 2 were 0.30, 2.08 Yuan and 2.38 Yuan in the 4% "Luo-wei" group, 0.20, 1.10 Yuan and 1.32 Yuan in the 50% NESWP group, and 0.17, 1.04 Yuan and 0.97 Yuan in the 26% MNSC group respectively, and the cost-effectiveness was the highest at the first spraying in all the three groups., Conclusions: The effects of the three molluscicides for snail control are similar, but the efficacy of snail control is reduced as the spraying time increases.

Background: The aim of the study was to investigate the effect associated with the protein expression of VEGF, JAK2 and STAT3 on the clinicopathologic characteristics and prognosis in the development and progression of nasopharyngeal carcinoma (NPC)., Methods: Fifty NPC patients in addition to 20 patients with chronic nasopharyngitis (CNP) were recruited for the purposes of the study. Western blotting and immunohistochemistry methods were employed to evaluate the protein expressions of JAK2, STAT3 and VEGF in the NPC and CNP tissues, with their respective correlations with the clinicopathologic characteristics of NPC patients subsequently analyzed. Spearman's rank correlation coefficient and Kaplan-Meier method were conducted to evaluate the respective correlations of JAK2, STAT3 and VEGF with NPC as well as the survival rates of patients with NPC. Cox regression analyses was performed in determine the prognostic NPC factors., Results: Compared with the CNP tissues, the NPC tissues exhibited elevated levels of JAK2, STAT3 and VEGF which were subsequently determined to share a positive correlation with T stages, lymph node metastasis (LNM), N stages and clinical stages, while a negative correlation with survival rates were observed in the NPC patients. Positive correlations between the expressions of JAK2, STAT3 and VEGF were detected among the NPC tissues. NPC patients survival time with negative expressions of JAK2, STAT3 and VEGF were observed to be longer than that of NPC patients with positive expressions of JAK2, STAT3 and VEGF. T stage, LNM, N stage, clinical stage. The expressions of JAK2, STAT3 and VEGF were discovered to be independent risk factors associated with the prognosis of patients with NPC., Conclusion: The results obtained from the present study support the notion that higher expressions of JAK2, STAT3 and VEGF may be correlated with the clinicopathologic characteristics and prognosis of patients suffering from NPC.

Purpose Pembrolizumab provides durable antitumor activity in metastatic melanoma, including complete response (CR) in about 15% of patients. Data are limited on potential predictors of CR and patient disposition after pembrolizumab discontinuation after CR. We describe baseline characteristics and long-term follow-up in patients who experienced CR with pembrolizumab in the KEYNOTE-001 study ( ClinicalTrials.gov identifier: NCT01295827). Patients and Methods Patients with ipilimumab-naive or -treated advanced/metastatic melanoma received one of three dose regimens of pembrolizumab. Eligible patients who received pembrolizumab for ≥ 6 months and at least two treatments beyond confirmed CR could discontinue therapy. Response was assessed every 12 weeks by central Response Evaluation Criteria in Solid Tumors version 1.1. For this analysis, CR was defined per investigator assessment, immune-related response criteria, and potential predictors of CR were evaluated using univariate and multivariate analyses. Results Of 655 treated patients, 105 (16.0%) achieved CR after median follow-up of 43 months. At data cutoff, 92 patients (87.6%) had CR, with median follow-up of 30 months from first CR. Fourteen (13.3%) patients continued to receive treatment for a median of ≥ 40 months. Pembrolizumab was discontinued by 91 patients (86.7%), including 67 (63.8%) who proceeded to observation without additional anticancer therapy. The 24-month disease-free survival rate from time of CR was 90.9% in all 105 patients with CR and 89.9% in the 67 patients who discontinued pembrolizumab after CR for observation. Tumor size and programmed death-ligand 1 status were among the baseline factors independently associated with CR by univariate analysis. Conclusion Patients with metastatic melanoma can have durable complete remission after discontinuation of pembrolizumab, and the low incidence of relapse after median follow-up of approximately 2 years from discontinuation provides hope for a cure for some patients. The mechanisms underlying durable CR require further investigation.

Metabolic defects are common pathological phenomena following traumatic brain injury (TBI) which contribute to poor prognosis. Brain-derived neurotrophic factor (BDNF) is an important regulator of neuronal survival, development, function, and plasticity. This study was designed to investigate the potential effects of BDNF on TBI-induced metabolic defects and their underlying molecular mechanisms. BDNF was added into cultured neurons to a concentration of 25, 50, and 100 ng/ml, respectively, right after mechanical injury and metabolite levels were analyzed 4 h post injury. The mitochondrial phosphorylated cAMP response element-binding protein (pCREB) distribution and complex V synthesis, as well as their roles in metabolic defects, were evaluated. We found that exogenous BDNF improved metabolic defects, especially the uncoupling of oxidative phosphorylation. BDNF increased pCREB in mitochondrial inner membrane and matrix and promoted mitochondrial complex V synthesis. We also found that these results were negatively regulated by the mitochondrial permeability transition pore (MPTP) antagonist CsA and positively regulated by the MPTP agonist atractyloside. BDNF's protectional effects on metabolic defects were abolished by CREB knockout. When administrated in a dominant interfering CREB mutant (A-CREB) model, mitochondrial pCREB accumulation could still be observed, but the synthesis of complex V and alleviation of metabolic defects were repressed. Our data demonstrate that exogenous BDNF mitigates neuronal metabolic defects following mechanical injury by promoting the pCREB accumulation in mitochondrial inner membrane and matrix, which is regulated by MPTP opening, thus facilitating the synthesis of mitochondrial complex V.

Objectives: The aims of this study were to measure diameters of the cricoid ring and left main bronchus in Asian adult patients and to assess the accuracy of double lumen tube size selected according to cricoid and left main bronchus diameter, respectively., Design: Retrospective observational study., Setting: Academic, tertiary care hospital., Participants: Preoperative CT scans from 87 men and 94 women who had undergone general anesthesia for lung operations., Interventions: No intervention., Measurements and Main Results: The diameters of the cricoid ring and left main bronchus were measured from thoracic computed tomography images after correction of slant. The "best-fit" size of double lumen tube was determined by comparing diameter of the left main bronchus and cricoid ring with the diameter of the double lumen tube. Diameters of the cricoid ring and left main bronchus were both significantly greater in men compared with women (p < 0.0001). Shapes of cricoid rings were different between genders (p < 0.0001), while shapes of the left main bronchus were not significant different (p = 0.343). With reference to the "best fit" size, the rate of agreement of cricoid ring size, left main bronchus size, and height size for men were 100%, 100%, and 94.3%. For women, the rate of agreement of cricoid ring size, left main bronchus size, and height size were 94.7%, 63.8%, and 51.1%., Conclusions: The "best fit" size of a double lumen tube should be decided by a combination of diameters of the cricoid ring and the left main bronchus., (Copyright © 2017 Elsevier Inc. All rights reserved.)