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In this study, we investigated the occurrence of organophosphate esters (OPEs) in the surface water and sediments of the Xiangjiang (XJ) River, a drinking water source of Changsha City. The total concentrations of five detected OPEs (Σ 5 OPEs) in surface water and tap water were 6.07-25.3 ng L -1 (average 14.9 ± 4.98 ng L -1 ), and 23.6 ng L -1 , respectively, and four detected OPEs (Σ 4 OPEs) in sediments were 3.74-27.5 ng g -1 dw (average 12.1 ± 6.48 ng g -1 dw). Tris-2-chloroisopropyl phosphate (TCIPP) was the dominant contributor in water and sediment samples, accounting for over 40% of ΣOPEs. A particular flood event during July-August 2020 reduced the level of OPEs in river water, leading to generally uniform OPE concentrations in surface water and sediment samples from the upper, middle, and lower reaches of XJ. Principal component analysis-multiple linear regression (PCA-MLR) results indicated that the main sources of OPEs in the surface water and sediments of XJ were emissions of waste-water treatment plants and anthropocentric activities. The results of ecological and human health risk assessments indicated that all OPEs posed a low or negligible ecological risk for algae, daphnia, and fish, and negligible risk for human health. Interestingly, the concentration and human health risk of OPEs in a composite tap water sample was generally higher than those in river water samples, indicating possible OPE contamination from water treatment processes or transportation through pipe networks., 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 © 2021 Elsevier B.V. All rights reserved.)

Background: Adequate flap volume is key to maintaining oral function after oral cancer surgery. This study aimed to evaluate changes in radial forearm free flap (RFFF) volumes after 1 year of follow-up following ablative tumor surgery in the head and neck., Methods: A prospective study that recorded the clinical data of 20 patients with head and neck cancer who underwent RFFF reconstruction. Magnetic resonance (MR) and Mimics Research 19.0 software were used to measure the RFFF volumes at 1, 3, 6, and 12 postoperative months., Results: Compared with one postoperative month, the RFFF volume decreased by 15.5%, 29.4%, and 42.0% at 3, 6, and 12 months, respectively, after surgery. A significant positive correlation between postoperative radiotherapy and RFFF volume changes was detected., Conclusion: The volume of RFFF decreases with time. It is recommended to use overcorrection, with a 40% increase in RFFF volume, to reconstruct head and neck tumor-related defects., (© 2021 Wiley Periodicals LLC.)

Organophosphate esters (OPEs) are typical industrial additives widely applied in various industrial and household products, but they may pollute drinking water. In the present study, the occurrence of OPEs in drinking water was analyzed. For this purpose, 25 drinking water samples were collected from households in 25 cities in China. The concentrations of OPEs were accurately determined according to a high-throughput organic analysis testing combined with high-volume solid phase extraction (Hi-throat/Hi-volume SPE) technique. Through this technique, nine OPEs were detected, with spiked recoveries from 77% to 101%, and their total concentrations (ΣOPEs) ranging from 46.8 to 251 (average 126) ng L -1 . The detection frequencies of the selected OPEs determined via Hi-throat/Hi-volume SPE were 88.0%-100%, which are much higher than those previously reported. The limit of detections of the OPEs was low at < 0.01 ng L -1 , which could be mainly attributed to the high volume of accumulated drinking water (>20 L). OPEs in drinking water presented a decreasing trend from cities in coastal provinces to inland cities of China. Redundancy analysis showed that the concentrations of OPEs in drinking water were significantly influenced by economic-demographic influencing factors. The non-carcinogenic and lifetime carcinogenic risks (non-CR and CR) of the analyzed OPEs in drinking water were negligible for urban residents in China., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To analyze the hub genes affecting the solely bone marrow relapse of childish acute B-cell lymphoblastic leukemia (B-ALL)., Methods: The high-throughput RNA sequencing data were downloaded from TCGA database, the differentially expressed genes were screened by DESeq2 package of R, and the differentially expressed genes were grouped by GO function enrichment analysis and KEGG pathway enrichment analysis. Further, the data of STRING database and Cytoscape software were used to construct protein interaction network, screen hub genes and highly interaction protein sub network, perform GO and KEGG analysis of the hub genes and protein sub network respectively. JASPAR database was used to screen the upstream transcription factor of the hub gene promoter. Survival analysis based on the expression of hub genes was performed with clinical information attached to TCGA database. The bone marrow samples and clinical data of the patients were collected, the analysis results of hub genes were verified through clinical samples., Results: 847 differentially expressed genes were collected, including 813 up-regulated genes, 34 down-regulated genes, 11 hub genes were screened out. The results of survival analysis showed that RPS5、RPS15、RPL23、RPL35、RPS8、RPS27A、RPS3、RPL9、RPS21、RPS7 and RPL38 showed significant effect on the survival of the children, and ZNF460 might be involved in their regulation. The high expressions of RPS3, RPS15, RPS8, RPS27A, and RPS21 had been verified in clinical samples of solely bone marrow relapsed patients., Conclusion: RPS3, RPS15, RPS8, RPS27A, RPS21 can be used as biomarkers to indicate the malignant event of solely bone marrow relapse, which may be regulated by ZNF460.

Traumatic brain injury (TBI) is the leading cause of mortality and disability in young people and may lead to the development of progressive neurodegeneration, such as that observed in chronic traumatic encephalopathy. We have recently found that the conformation-specific cis phosphorylated form of tau (cis P-tau) is a major early driver of neurodegeneration after TBI. However, not much is known about how cis P-tau is regulated in TBI. In this study, we demonstrated a novel critical role of death-associated protein kinase 1 (DAPK1) in regulating cis P-tau induction after TBI. We found that DAPK1 is significantly upregulated in mouse brains after TBI and subsequently promotes cis P-tau induction. Genetic deletion of DAPK1 in mice not only significantly decreases cis P-tau expression, but also effectively attenuates neuropathology development and rescues behavioral impairments after TBI. Mechanistically, DAPK1-mediated cis P-tau induction is regulated by the phosphorylation of Pin1 at Ser71, a unique prolyl isomerase known to control the conformational status of P-tau. Furthermore, pharmacological suppression of DAPK1 kinase activity dramatically decreases the levels of Pin1 phosphorylated at Ser71 as well as cis P-tau after neuronal stress. Thus, DAPK1 is a novel regulator of TBI that, in combination with its downstream targets, has a major impact on the development and/or outcome of TBI, and targeting DAPK1 might offer a potential therapeutic impact on TBI-related neurodegenerative diseases., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Genetic testing is the gold standard for exploring the etiology of congenital hearing loss. Here, we enrolled 137 Chinese patients with congenital hearing loss to describe the molecular epidemiology by using 127 gene panel testing or 159 variant testing. Sixty-three deaf children received 127 gene panel testing, while seventy-four patients received 159 variant testing. By use of 127 gene panel testing, more mutant genes and variants were identified. The most frequent mutant genes were GJB2 , SLC26A4 , MYO15A , CDH23 , and OTOF . By analyzing the patients who received 127 gene panel testing, we found that 51 deaf children carried variants which were not included in 159 variant testing. Therefore, a large number of patients would be misdiagnosed if only 159 variant testing is used. This study highlights the advantage of 127 gene panel testing, and it suggests that broader genetic testing should be done to identify the genetic etiology of congenital hearing loss., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 Le Xie et al.)

Background: When redox balance is lost in the brain, oxidative stress can cause serious damage that leads to neuronal loss, in congruence with neurodegenerative diseases. Aucubin (AU) is an iridoid glycoside and that is one of the active constituents of Eucommia ulmoides, has many pharmacological effects such as anti-inflammation, anti-liver fibrosis, and anti-atherosclerosis., Purpose: The present study aimed to evaluate the inhibitory effects of AU on cell oxidative stress against hydrogen peroxide (H 2 O 2 )-induced injury in SH-SY5Y cells in vitro., Methods: SH-SY5Y cells were simultaneously treated with AU and H 2 O 2 for 24 h. Cell viability was measured by CCK-8. Additionally, mitochondrial membrane depolarization, reactive oxygen species (ROS) generation, and cell apoptosis were measured by flow cytometry., Results: The results showed that AU can significantly increase the H 2 O 2 -induced cell viability and the mitochondrial membrane potential, decrease the ROS generation, malondialdehyde (MDA), and increase glutathione (GSH) contents and the superoxide dismutase (SOD) activity. We also found that H 2 O 2 stimulated the production of nitric oxide (NO), which could be reduced by treatment with AU through inhibiting the inducible nitric oxide synthase (iNOS) protein expression. In H 2 O 2 -induced SH-SY5Y cells, the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) content and cell apoptosis were significantly reduced by AU treatment through nuclear factor E2-related factor 2/hemo oxygenase-1 (Nrf2/HO-1) activation, inhibiting the expression of p-NF-κB/NF-κB and down-regulating MAPK and Bcl-2/Bax pathways., Conclusion: These results indicate that AU can reduce inflammation and oxidative stress through the NF-κB, Nrf2/HO-1, and MAPK pathways., (Copyright © 2021. Published by Elsevier GmbH.)

The aim of the present study was to assess the practical diagnostic value of whole-exome sequencing (WES) in patients with different phenotypes and to explore possible strategies to increase the capability of WES in identifying disease-causing genes. A total of 1,360 patients (aged from 1 day to 42 years old) with manifestations of genetic diseases were genotyped using WES and statistical analysis was performed on the results obtained. Within this cohort, the overall positive rate of identification of a disease-causing gene alteration was 44.41%. The positive identification rate where trio-samples were used (from the proband and both parents) was higher than that where a single proband sample was used (50.00 vs. 43.71%), and 604 positive cases with 150 genetic syndromes, 510 genes and 718 mutations were detected. Missense mutations were the most common variations (n=335, 45.27%) and visual or auditory abnormalities (58.51%) had the highest rate of association with a genetic abnormality. The positive detection rate of WES was elevated with the increase in the number of clinical symptoms from 1 to 8. The present study indicated that WES may be used as a valuable tool in the clinic and the positive rate depends more on the professional experience of clinicians rather than on the analytical capabilities of the data analyst. At the same time, particular attention must be paid to certain possible factors (such as the age of the patients as well as possible exon deletions), which may affect the diagnostic rate while applying this process., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Zhang et al.)

Background: With the gradual popularity of relatively novel medial sural artery perforator flap (MSAPF), robust studies are needed to compare the surgical outcomes of MSAPF versus multiple free soft flaps (MFSFs) to verify the advantages and disadvantages of MSAPF., Methods: The authors searched PubMed, Web of Science, EMBASE, Cochrane Library, Chinese BioMedical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI) until September, 2020, to identify studies that compared surgical outcomes of MSAPF and MFSFs. Two authors followed the PRISMA guidelines, individually extracted the data and performed the quality assessments. Survival rate of flaps, satisfaction degree of patients in recipient and donor site, skin grafting, and morbidity of recipient and donor site were evaluated., Results: A total of 441 cases from 7 studies were included in our analysis. No significant differences were found regarding survival rate of flaps, recipient morbidity, and recipient satisfaction degree between the 2 groups. However, MSAPF group was significantly superior to MFSFs group in terms of skin grafting, morbidity, and satisfaction degree of donor site., Conclusion: Our meta-analysis showed that the MSPAF and MFSFs groups were similar in terms of survival rate of flaps, recipient morbidity, and recipient satisfaction degree. Medial sural artery perforator flap group was superior to MFSFs group in terms of morbidity and satisfaction degree of donor site. The results may prove that MSAPF is gaining popularity for a reason and is a good choice for repairing soft tissue defects., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by Mutaz B. Habal, MD.)

Background: To determine risk factors for intestinal necrosis in intussusception cases among children with failed non-surgical reduction for intussusception., Methods: Totally, 540 hospitalized individuals with unsuccessful air-enema reduction in our hospital between November 2010 and November 2020 were assessed in this retrospective study. The 540 intussusception cases were divided into the intestinal necrosis and non-intestinal necrosis groups. Haemostatic parameters, demographic and clinical features were assessed. Predictors of intestinal necrosis were examined by univariable and multivariable logistic regression analyses., Results: Of the 540 patients included, 113 showed intestinal necrosis. This intestinal necrosis group had a longer duration of symptom or length of illness, younger ages, higher platelet counts, fibrinogen amounts and d-dimer levels (all P = 0.000) compared with the non-intestinal necrosis group. Multivariable analysis revealed that duration of symptom (odds ratio (OR) 1.12; 95% confidence interval (CI) 1.16-1.23, P = 0.000), fibrinogen (OR 1.26; 95% CI 1.10-1.31, P = 0.010) and d-dimer (OR 2.07; 95% CI 1.91-2.28, P = 0.000) independently predicted intestinal necrosis in individuals undergoing surgical reduction for intussusception. Receiver operating characteristic curve analysis showed that d-dimer amounts had the largest area under the curve for predicting intestinal necrosis., Conclusion: On admission, long duration of symptom, high fibrinogen and d-dimer levels are critical risk factors for intestinal necrosis development in children with unsuccessful non-surgical reduction. d-Dimer levels have the best predictive value for intestinal necrosis., (© 2021 Royal Australasian College of Surgeons.)

Immunotherapy has revolutionized cancer treatment, however, not all tumor types and patients are completely responsive to this approach. Establishing predictive pre-clinical models would allow for more accurate and practical immunotherapeutic drug development. Mouse models are extensively used as in vivo system for biomedical research. However, due to the significant differences between rodents and human, it is impossible to translate most of the findings from mouse models to human. Pharmacological development and advancing personalized medicine using patient-derived xenografts relies on producing mouse models in which murine cells and genes are substituted with their human equivalent. Humanized mice (HM) provide a suitable platform to evaluate xenograft growth in the context of a human immune system. In this review, we discussed recent advances in the generation and application of HM models. We also reviewed new insights into the basic mechanisms, pre-clinical evaluation of onco-immunotherapies, current limitations in the application of these models as well as available improvement strategies. Finally, we pointed out some issues for future studies., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objective: To quantitatively study the biomechanical parameters of Bachuorounian manipulation in the treatment of humeral epicondylitis, and discuss the effects of individual characteristics on the biomechanical parameters were discussed., Methods: From July 2019 to February 2020, 40 patients with external humeral epicondylitis were selected, including 18 males and 22 females, ranging in age from 20 to 50 years old, with an average of (34.37±8.41) years old;and the course of disease ranged from 1 to 11 months, with a mean of (6.05±2.71) months. The biomechanical parameters of the elbow joint of the affected side were measured by using the biomechanical sensor. At thesame time, the individual characteristic parameters of patients were collected to analyze the influence of different individual characteristics of patients on biomechanical parameters., Results: The results of mechanical analysis in each stage of the bachuorounian manipulation were as follows:the rolling back rotation force was (31.17±2.99) N;the buckling bending drawing force was (44.99±2.38) N;the rolling pre rotation force was (31.03±2.75) N;and stretching drawing force was (48.75±2.09) N. The correlation analysis between the parameters showed that there was a significant positive correlation between the buckling bending drawing force and the stretching drawing force parameters, and a significant positive correlation between the rolling force back-rotation force and the rolling pre-rotation force parameters. The multivariate linear regression analysis on the parameters of influencing factors and manipulative biomechanics showed that there was a significant correlation between body weight and rolling back-rotation force, significant correlation between elbow tenderness and the buckling bending drawing force, and significant correlation between disease duration and the stretching drawing force., Conclusion: The bachuorounian manipulation of humeral epicondylitis has a certain range of operating force. Manipulation of each stage has a correlation and systematic. The patient's weight, elbow tenderness and disease course are important factors affecting the bachuorounian manipulation.

Background: Subclinical hypothyroidism (SCH) has recently been acknowledged as an independent risk factor for coronary artery disease (CAD). However, the characteristics of CAD in patients with SCH are not fully understood. This study aims to evaluate the features of CAD in patients with SCH using coronary computed tomographic angiography (CCTA)., Materials and Methods: From 1 April, 2018 to 30 June, 2020, 234 consecutive SCH patients with coronary plaques identified on CCTA were included retrospectively. They were further subdivided into different degree of SCH groups (mild SCH vs. moderate SCH vs. severe SCH: 143 vs 62 vs 28) and different gender groups (men with SCH vs. women with SCH:116 vs 118). The distributions and types of plaques, luminal narrowing, segment involvement scores (SIS) and segment stenosis scores (SSS) were evaluated and compared among the different groups., Results: Patients with severe SCH had fewer calcified plaques (0.7 ± 0.9 vs. 2.0 ± 1.9, p < 0.001) and more non-calcified plaques (0.9 ± 1.0 vs. 0.3 ± 0.5, p < 0.001) than those with mild SCH. As the SCH condition worsened, the proportion of non-calcified plaques significantly increased. Whereas there were no significant discrepancies in SIS and SSS among patients with different grades of SCH (all p > 0.05). Men with SCH had higher SIS (3.9 ± 2.3 vs. 3.0 ± 2.3, p = 0.004) and SSS (7.8 ± 5.4 vs. 5.4 ± 3.0, p = 0.002) than women. Multivariate logistic and linear regression analysis demonstrated that grades of SCH (Moderate SCH, odds ratio [OR] 2.11; 95% CI 1.03-4.34, p = 0.042; severe SCH, OR: 10.00; 95% CI 3.82-26.20, p < 0.001, taken mild SCH as a reference) was independently associated with the presence of non-calcified plaques, whereas sex (B: 1.67; 95% CI 0.27-3.10, p = 0.009) was independently associated with SSS., Conclusions: Severe SCH is associated with non-calcified plaques, and men with SCH have higher total plaque burden than women. We suggest that it is important to evaluate for coronary plaque in SCH patients, especially those with severe SCH and men with SCH.

Artificial intelligence (AI) transforms medical images into high-throughput mineable data. Machine learning algorithms, which can be designed for modeling for lesion detection, target segmentation, disease diagnosis, and prognosis prediction, have markedly promoted precision medicine for clinical decision support. There has been a dramatic increase in the number of articles, including articles on ultrasound with AI, published in only a few years. Given the unique properties of ultrasound that differentiate it from other imaging modalities, including real-time scanning, operator-dependence, and multi-modality, readers should pay additional attention to assessing studies that rely on ultrasound AI. This review offers the readers a targeted guide covering critical points that can be used to identify strong and underpowered ultrasound AI studies., 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 Kuang, Hu, Li, Chen and Lu.)

Background: We aimed to explore the value of combining real-time three-dimensional echocardiography (RT-3DE) and myocardial contrast echocardiography (MCE) in the left ventricle (LV) evaluating myocardial dysfunction in type 2 diabetes mellitus (T2DM) patients. Patients and Methods: A total of 58 T2DM patients and 32 healthy individuals were selected for this study. T2DM patients were further divided into T2DM without microvascular complications ( n = 29) and T2DM with microvascular complications ( n = 29) subgroups. All participants underwent RT-3DE and MCE. The standard deviation (SD) and the maximum time difference (Dif) of the time to the minimum systolic volume (Tmsv) of the left ventricle were measured by RT-3DE. MCE was performed to obtain the perfusion measurement of each segment of the ventricular wall, including acoustic intensity (A), flow velocity (β), and A·β. Results: There were significant differences in all Tmsv indices except for Tmsv6-Dif among the three groups (all P < 0.05). After heart rate correction, all Tmsv indices of the T2DM with microvascular complications group were prolonged compared with the control group (all P < 0.05). The parameters of A, β, and A·β for overall segments showed a gradually decreasing trend in three groups, while the differences between the three groups were statistically significant (all P < 0.01). For segmental evaluation of MCE, the value of A, β, and A·β in all segments showed a decreasing trend and significantly differed among the three groups (all P < 0.05). Conclusions: The RT-3DE and MCE can detect subclinical myocardial dysfunction and impaired myocardial microvascular perfusion. Left ventricular dyssynchrony occurred in T2DM patients with or without microvascular complications and was related to left ventricular dysfunction. Myocardial perfusion was reduced in T2DM patients, presenting as diffuse damage, which was aggravated by microvascular complications in other organs., 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 Li, Lv, Liu, Zeng, Ye, Li, Fan, Lin, Huang and Yao.)

Contrary to conventional Tamm plasmon (TP) absorbers of which narrow absorptance peaks will shift toward short wavelengths (blueshift) as the incident angle increases for both transverse magnetic (TM) and transverse electric (TE) polarizations, here we theoretically and experimentally achieve nonreciprocal absorption in a planar photonic heterostructure composed of an isotropic epsilon-near-zero (ENZ) slab and a truncated photonic crystal for TM polarization. This exotic phenomenon results from the interplay between ENZ and material loss. And the boundary condition across the ENZ interface and the confinement effect provided by the TP can enhance the absorption in the ENZ slab greatly. As a result, a strong and nonreciprocal absorptance peak is observed experimentally with a maximum absorptance value of 93% in an angle range of 60∼70°. Moreover, this TP absorber shows strong angle-independence and polarization-dependence. As the characteristics above are not at a cost of extra nanopatterning, this structure is promising to offer a practical design in narrowband thermal emitter, highly sensitive biosensing, and nonreciprocal nonlinear optical devices.

Compelling evidence supports vascular contributions to cognitive impairment and dementia (VCID) including Alzheimer's disease (AD), but the underlying pathogenic mechanisms and treatments are not fully understood. Cis P-tau is an early driver of neurodegeneration resulting from traumatic brain injury, but its role in VCID remains unclear. Here, we found robust cis P-tau despite no tau tangles in patients with VCID and in mice modeling key aspects of clinical VCID, likely because of the inhibition of its isomerase Pin1 by DAPK1. Elimination of cis P-tau in VCID mice using cis-targeted immunotherapy, brain-specific Pin1 overexpression, or DAPK1 knockout effectively rescues VCID-like neurodegeneration and cognitive impairment in executive function. Cis mAb also prevents and ameliorates progression of AD-like neurodegeneration and memory loss in mice. Furthermore, single-cell RNA sequencing revealed that young VCID mice display diverse cortical cell type-specific transcriptomic changes resembling old patients with AD, and the vast majority of these global changes were recovered by cis-targeted immunotherapy. Moreover, purified soluble cis P-tau was sufficient to induce progressive neurodegeneration and brain dysfunction by causing axonopathy and conserved transcriptomic signature found in VCID mice and patients with AD with early pathology. Thus, cis P-tau might play a major role in mediating VCID and AD, and antibody targeting it may be useful for early diagnosis, prevention, and treatment of cognitive impairment and dementia after neurovascular insults and in AD., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Pancreatic cancer is a highly malignant type of cancer and its treatment remains a major challenge. The novel recombinant protein TNF-related apoptosis-inducing ligand (TRAIL)-Mu3 has been shown to exert stronger tumor inhibitory effects in colon cancer in vitro and in vivo compared with TRAIL. The present study investigated the antitumor effects of TRAIL-Mu3 on pancreatic cancer cells, and the possible mechanisms were further examined. Compared with TRAIL, TRAIL-Mu3 exhibited significantly higher cytotoxic effects on pancreatic cancer cell lines. The inhibitory effect of TRAIL-Mu3 on the viability of PANC-1 cells was shown to be a caspase-dependent process. The affinity of TRAIL-Mu3 to PANC-1 cell membranes was significantly enhanced compared with TRAIL. In addition, TRAIL-Mu3 upregulated death receptor (DR) expression in PANC-1 cells and promoted the redistribution of DR5 in lipid rafts. Western blotting results demonstrated that TRAIL-Mu3 activated the caspase cascade in a faster and more efficient manner compared with TRAIL in PANC-1 cells. Therefore, TRAIL-Mu3 enhanced the antitumor effects in pancreatic cancer cells by strengthening the apoptotic signaling pathway. The present study indicated the potential of TRAIL-Mu3 for the treatment of pancreatic cancer., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Huang et al.)

Objective: To study the clinical features and prognosis of children with acute megakaryocytic leukemia (AMKL) and the clinical effect of acute myeloid leukemia 03 (AML03) regimen for the treatment of pediatric AMKL., Methods: The clinical data were collected from 47 children with AMKL who were diagnosed from May 2011 to December 2019. The treatment outcomes and prognostic factors were analyzed. The Kaplan-Meier method and the log-rank test were used for survival analysis., Results: Among the 47 children with AMKL, 22 with non-Down syndrome-AMKL were treated by the AML03 regimen, with a median follow-up time of 11.4 months. For the 22 non-Down syndrome-AMKL patients, the remission rate of bone marrow cytology was 85% and the negative rate of minimal residual disease (MRD) was 79% after induction Ⅱ, with a 2-year overall survival (OS) rate of (50±13)% and a 2-year event-free survival (EFS) rate of (40±12)%. The group with positive immunophenotypic marker CD56 had significantly lower 2-year EFS and OS rates than the group with negative CD56 ( P < 0.05). The group without remission of bone marrow cytology after induction Ⅱ had significantly lower 2-year EFS and OS rates than the group with remission ( P < 0.05). The group with positive MRD after induction Ⅱ had a significantly lower 2-year EFS rate than the group with negative MRD ( P < 0.05). There was no significant difference in 2-year OS and EFS rates between the patients with transplantation and those without transplantation ( P > 0.05)., Conclusions: Children with AMKL tend to have a low remission rate and a poor prognosis. Positive immunophenotypic marker CD56, bone marrow cytology during early treatment response, and MRD results are important factors influencing the prognosis. Allogeneic hematopoietic stem cell transplantation has no significant effect on the prognosis of AMKL.

Engineering nanoheterostructures (NHs) plays a key role in exploring novel or enhanced physicochemical properties of nanocrystals. Despite previously reported synthetic methodologies, selective synthesis of NHs to achieve the anticipated composition and interface is still challenging. Herein, we presented a colloidal strategy for the regioselective construction of typical Ag-Co 2 P NHs with precisely controlled location of Ag nanoparticles (NPs) on unique chemically transformed Co 2 P nanorods (NRs) by simply changing the ratio of different surfactants. As a proof-of-concept study, the constructed heterointerface-dependent hydrogen evolution reaction (HER) catalysis was demonstrated. The multiple Ag NP-tipped Co 2 P NRs exhibited the best HER performance, due to their more exposed active sites and the synergistic effect at the interfaces. Our results open up new avenues in rational design and fabrication of NHs with delicate control over the spatial distribution and interfaces between different components.

As an important trace element, iron plays an essential role in many biology processes like cell proliferation, metabolism, and mitochondrial function. However, the disruption of iron homeostasis tends to cells death and human diseases due to it servers as mediator to promote the production of reactive oxygen species (ROS). In this review, first we introduced the mechanism of complex iron-mediated ROS involved in apoptosis, necroptosis, ferroptosis and pyroptosis. Next, we discussed the controversial role of excess iron and iron deficiency in tumor. Finally, we discussed the anti-cancer effects of iron on both sides, and novel iron-related strategies. This review outlined the mechanisms and regulation of iron homeostasis and iron-mediated ROS in tumors, and discussed the iron-related treatments., Competing Interests: None., (AJCR Copyright © 2021.)

Bisphenol A (BPA) is a well-known xenoestrogen, and UV/H 2 O 2 advanced oxidation process (AOP) is one of the most effective technologies to remove BPA from water. Using BPA spiked tap water, a batch-scale photochemical experiment was conducted to investigate whether BPA can pose a genotoxicity concern during the medium pressure (MP) UV/H 2 O 2 treatment and the post-chloramination. Samples at different UV exposure and post-chloramination durations were collected and analyzed by CALUX® gene reporter assays regarding estrogen receptor α (ERα) and p53 transcriptional activity. MP UV/H 2 O 2 process did not cause extra estrogenic effects from the degradation of BPA, whereas genotoxicity occurred when the treated water was exposed with monochloramine. Seven frequently reported nitrogenous disinfection byproducts (N-DBPs) were detected, but none of them were responsible for the observed genotoxicity. Employed with gas chromatography-quadrupole time-of-flight mass spectrometry (GC-QTOF-MS), four compounds possibly contributed to the genotoxicity were tentatively identified and two of them with aminooxy- or cyano- group were considered as "new" N-DBPs. This study demonstrated that by-products differ from their parent compounds in toxicity can be formed in the UV oxidation with post-disinfection process, which should become a cause for concern., Competing Interests: Declaration of competing interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Congenital deafness is one of the most common causes of disability in humans, and more than half of cases are caused by genetic factors. Mutations of the MYO15A gene are the third most common cause of hereditary hearing loss. Using next-generation sequencing combined with auditory tests, two novel compound heterozygous variants c.2802&#95;2812del/c.5681T>C and c.5681T>C/c.6340G>A in the MYO15A gene were identified in probands from two irrelevant Chinese families. Auditory phenotypes of the probands are consistent with the previously reported for recessive variants in the MYO15A gene. The two novel variants, c.2802&#95;2812del and c.5681T>C, were identified as deleterious mutations by bioinformatics analysis. Our findings extend the MYO15A gene mutation spectrum and provide more information for rapid and precise molecular diagnosis of congenital deafness., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 Xiao-Hui Wang et al.)

Pin1 is a unique isomerase that regulates protein conformation and function after phosphorylation. Pin1 aberration contributes to some neurological diseases, notably Alzheimer's disease, but its role in epilepsy is not fully understood. We found that Pin1-deficient mice had significantly increased seizure susceptibility in multiple chemical inducing models and developed age-dependent spontaneous epilepsy. Electrophysiologically, Pin1 ablation enhanced excitatory synaptic transmission to prefrontal cortex (PFC) pyramidal neurons without affecting their intrinsic excitability. Biochemically, Pin1 ablation upregulated AMPA receptors and GluA1 phosphorylation by acting on phosphorylated CaMKII. Clinically, Pin1 was decreased significantly, whereas phosphorylated CaMKII and GluA1 were increased in the neocortex of patients with epilepsy. Moreover, Pin1 expression restoration in the PFC of Pin1-deficient mice using viral gene transfer significantly reduced phosphorylated CaMKII and GluA1 and effectively suppressed their seizure susceptibility. Thus, Pin1-CaMKII-AMPA receptors are a novel axis controlling epileptic susceptibility, highlighting attractive new therapeutic strategies., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

This study aimed to explore whether APOC1 expression has a function in the biological behavior of clear cell renal cell carcinoma (ccRCC) cells and its possible mechanism. Bioinformatics analysis of data TCGA and OnComine was conducted to explore the expression pattern and prognostic value of APOC1, as well as the relationship between APOC1 expression and clinical indicators. Loss- and gain- of APOC1 function assays were carried out to assess the biological functions of APOC1. Western blotting was applied to detect protein expression. We revealed that APOC1 was upregulated in ccRCC tissues. APOC1 expression was related to gender, grade, pathologic-T, pathologic-stage, and pathologic-M in patients with ccRCC. Meanwhile, Kaplan-Meier analysis evidenced that the high APOC1 expression indicated unfavorable outcomes of ccRCC. Functional experiments in vitro revealed that upregulation of APOC1 in UT33A cells promoted cell proliferation, invasion, and migration, while downregulation of APOC1 in 786-O cells had the opposite effect. Furthermore, epithelial mesenchymal transition (EMT) was activated in cells with upregulated APOC1 but inhibited in cells with down-regulated APOC1. Collectively, our data suggested that APOC1 was overexpressed in ccRCC cells and promoted the malignant biological behaviors and EMT of ccRCC cells., (© 2020 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

Realizing a polarization-insensitive broadband optical absorber plays a key role in the implementation of microstructure optoelectrical devices with on-demand functionalities. However, the challenge is that most of these devices involve the constituent metals, thus suffering from poor chemical and thermal stability and a complicated manufacturing process. In addition, the extreme contrast between the negative (metallic) and positive (dielectric) real parts of the constituent permittivities can cause additional problems in the design of structural devices. Based on these facts, this work proposes a design of planar broadband one-dimensional structure based on Fibonacci geometry. Experimental results show that the proposed planar structure exhibits high absorptivity behavior independent of polarization and angle in the wavelength range of 300-1000 nm. The absorptivity remains more than 80% when the incident angle is 60°. This proof-of-concept represents a new strategy for realizing non-metallic broadband optical absorbers with advantages of polarization-independence, low-cost, and wide-field-of-view and paves the way for light manipulation under harsh conditions.

Objective: Middle-age patients with retinal detachment (RD) exhibit a loss of visual information, and previous studies of functional magnetic resonance imaging (fMRI) have demonstrated abnormal spontaneous activity in the RD brain. Therefore, this study assessed changes in local functional connectivity density (lFCD) and long-range functional connectivity density (longFCD) in middle-age RD patients during resting-state FC., Methods: In total, 32 middle-age patients with RD (18 men and 14 women), and 32 age-, sex-, and education-matched normal controls (NCs) (18 men and 14 women) were recruited and underwent functional magnetic resonance examination in the resting state. Two-sample t test was performed to compare lFCD and longFCD between groups. Receiver operating characteristic (ROC) curves were generated to distinguish middle-age RD patients from NCs., Results: Compared with NCs, middle-age RD patients demonstrated increased lFCD values in the right inferior temporal gyrus, and increased longFCD values in the bilateral inferior frontal gyri, left superior and middle frontal gyrus, bilateral inferior temporal gyri, and left cerebellum posterior lobe. Middle-age RD patient exhibited decreased lFCD values in the left cuneus, right lingual gyrus, and left middle frontal gyrus. They also had lower longFCD values in the left lingual gyrus and left inferior occipital gyrus. ROC curve analysis showed excellent accuracy of the specific areas under the curve., Conclusion: Our results reveal that middle-age RD patients exhibited variations of binarized lFCD and longFCD in specific brain areas, which provides insight into the pathological mechanism of RD patients with acute visual loss., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: The typical enhancement patterns of hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS) are hyper-enhanced in the arterial phase and washed out during the portal venous and late phases. However, atypical variations make a differential diagnosis both challenging and crucial. We aimed to investigate whether machine learning-based ultrasonic signatures derived from CEUS images could improve the diagnostic performance in differentiating focal nodular hyperplasia (FNH) and atypical hepatocellular carcinoma (aHCC)., Patients and Methods: A total of 226 focal liver lesions, including 107 aHCC and 119 FNH lesions, examined by CEUS were reviewed retrospectively. For machine learning-based ultrasomics, 3,132 features were extracted from the images of the baseline, arterial, and portal phases. An ultrasomics signature was generated by a machine learning model. The predictive model was constructed using the support vector machine method trained with the following groups: ultrasomics features, radiologist's score, and combination of ultrasomics features and radiologist's score. The diagnostic performance was explored using the area under the receiver operating characteristic curve (AUC)., Results: A total of 14 ultrasomics features were chosen to build an ultrasomics model, and they presented good performance in differentiating FNH and aHCC with an AUC of 0.86 (95% confidence interval [CI]: 0.80, 0.89), a sensitivity of 76.6% (95% CI: 67.5%, 84.3%), and a specificity of 80.5% (95% CI: 70.6%, 85.9%). The model trained with a combination of ultrasomics features and the radiologist's score achieved a significantly higher AUC (0.93, 95% CI: 0.89, 0.96) than that trained with the radiologist's score (AUC: 0.84, 95% CI: 0.79, 0.89, P < 0.001). For the sub-group of HCC with normal AFP value, the model trained with a combination of ultrasomics features, and the radiologist's score remain achieved the highest AUC of 0.92 (95% CI: 0.87, 0.96) compared to that with the ultrasomics features (AUC: 0.86, 95% CI: 0.74, 0.89, P < 0.001) and radiologist's score (AUC: 0.86, 95% CI: 0.79, 0.91, P < 0.001)., Conclusions: Machine learning-based ultrasomics performs as well as the staff radiologist in predicting the differential diagnosis of FNH and aHCC. Incorporating an ultrasomics signature into the radiologist's score improves the diagnostic performance in differentiating FNH and aHCC., Competing Interests: XL was employed by GE Healthcare. The remaining 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 Li, Lv, Zheng, Ruan, Hu, Chen, Huang, Li, Zhang, Xie, Kuang, Lu, Zhuang and Wang.)

Objective: To investigate the clinical efficacy and superiority of direct lateral interbody fusion combined with posterior percutaneous screw fixation in the treatment of lumbar tuberculosis., Methods: From June 2013 to August 2016, the clinical data of 83 patients with lumbar tuberculosis were retrospectively analyzed, including 55 males and 28 females, aged from 27 to 72 (49.5±13.5) years. These 83 patients were divided into two groups according to different operation methods, 35 cases in group A were treated with direct lateral interbody fusion combined with posterior percutaneous screw fixation;48 cases in group B were treated with anterior traditional extraperitoneal debridement combined with posterior internal fixation. After operation, regular quadruple antituberculosis drugs were continued for 18 months. The operation time, intraoperative blood loss, hospital stay, bone graft fusion time and complications were compared between the two groups. Visual analogue score (VAS) of lumbar pain, Oswestry Disability Index (ODI), sagittal Cobb angle, erythrocyte sedimentation rate (ESR) and C-reactive protein(CRP) values before and after operation were analyzed., Results: The operation was successfully completed in both groups, and the operation mode was not changed during operation. The operation time, intraoperative blood loss and hospital stay were (149.4±13.3) min, (354.3±69.0) ml, (9.4±1.6) d in group A and(116.8±10.0) min, (721.9±172.3) ml, (11.8±1.7) d in group B, respectively, with significant difference between the two groups ( P <0.05). The follow up time was (24.2±5.1) months in group A and (24.0±5.0) months in group B, there was no significant difference between two groups ( P >0.05). At the follow-up of 4 months after operation, one patient in group A was found to have enlarged psoas major abscess on the contralateral side, and was cured after secondary operation. No sinus formation, cerebrospinal fluid leakage, internal fixation loosening, fracture or distal junction kyphosis were found during follow-up. The fusion time was (5.1±1.6) months in group A and (5.1± 1.7) months in group B, there was no significant difference between two groups ( P >0.05). The VAS, ODI score, sagittal Cobb angle, ESR and CRP value of the lesion segment at the last follow-up of the two groups were significantly improved ( P <0.05), but there was no significant difference between two groups ( P >0.05)., Conclusion: The two kinds of operation can obtain satisfactory clinical effect. Direct lateral interbody fusion combined with posterior percutaneous screw fixation can reduce intraoperative blood loss and hospital stay, which is conducive to early rehabilitation of patients.

Sudden sensorineural hearing loss (SSNHL) is a common emergency in the world. Increasing evidence of imbalance of oxidant-antioxidant were found in SSNHL patients. Steroids combined with antioxidants may be a potential strategy for the treatment of SSNHL. In cochlear explant experiment, we found that N-acetylcysteine (NAC) combined with dexamethasone can effectively protect hair cells from oxidative stress when they were both at ineffective concentrations alone. A clinic trial was designed to explore whether oral NAC combined with intratympanic dexamethasone (ITD) as a salvage treatment has a better therapeutic effect. 41 patients with SSNHL were randomized to two groups. 23 patients in control group received ITD therapy alone, while 18 patient s in NAC group were treated with oral NAC and ITD. The patients were followed-up on day 1st (initiation of treatment) and day 14th. Overall, there was no statistical difference in final pure-tone threshold average (PTA) improvement between those two groups. However, a significant hearing gain at 8,000 Hz was observed in NAC group. Moreover, the hearing recovery rates of NAC group is much higher than that in control group. These results demonstrated that oral NAC in combination with ITD therapy is a more effective therapy for SSNHL than ITD alone., 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 Bai, Chen, Xu, Jin, Niu, Xie, Qiu, Liu and Sun.)

Osteosarcoma (OS) is the most common primary bone malignancy in the adolescent population. MAFG (v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog G) forms a heterodimer with Nrf2 (NF-E2-related factor 2), binding to antioxidant response element (ARE), which is required for Nrf2 signaling activation. We found that MAFG mRNA and protein expression is significantly elevated in human OS tissues as well as in established and primary human OS cells. In human OS cells, MAGF silencing or knockout (KO) largely inhibited OS cell growth, proliferation, and migration, simultaneously inducing oxidative injury and apoptosis activation. Conversely, ectopic overexpression of MAFG augmented OS cell progression in vitro . MicroRNA-4660 (miR-4660) directly binds the 3' untranslated region (UTR) of MAFG mRNA in the cytoplasm of OS cells. MAFG 3' UTR luciferase activity and expression as well as OS cell growth were largely inhibited with forced miR-4660 overexpression but augmented with miR-4660 inhibition. In vivo , MAGF short hairpin RNA (shRNA) or forced overexpression of miR-4660 inhibited subcutaneous OS xenograft growth in severe combined immunodeficient mice. Furthermore, MAFG silencing or miR-4660 overexpression inhibited OS xenograft in situ growth in proximal tibia of the nude mice. In summary, MAFG overexpression-driven OS cell progression is inhibited by miR-4660. The miR-4660-MAFG axis could be novel therapeutic target for human OS., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

IL-4 induces Akt activation in macrophages, required for full M2 (alternative) polarization. We examined the roles of Gαi1 and Gαi3 in M2 polarization using multiple genetic methods. Methods and Results: In MEFs and primary murine BMDMs, Gαi1/3 shRNA, knockout or dominant negative mutations attenuated IL-4-induced IL4Rα endocytosis, Gab1 recruitment as well as Akt activation, leaving STAT6 signaling unaffected. Following IL-4 stimulation, Gαi1/3 proteins associated with the intracellular domain of IL-4Rα and the APPL1 adaptor, to mediate IL-4Rα endosomal traffic and Gab1-Akt activation in BMDMs. In contrast, gene silencing of Gαi1/3 with shRNA or knockout resulted in BMDMs that were refractory to IL-4-induced M2 polarization. Conversely, Gαi1/3-overexpressed BMDMs displayed preferred M2 response with IL-4 stimulation. In primary human macrophages IL-4-induced Akt activation and Th2 genes expression were inhibited with Gαi1/3 silencing, but augmented with Gαi1/3 overexpression. In Gαi1/3 double knockout (DKO) mice, M2 polarization, by injection of IL-4 complex or chitin, was potently inhibited. Moreover, in a murine model of asthma, ovalbumin-induced airway inflammation and hyperresponsiveness were largely impaired in Gαi1/3 DKO mice. Conclusion: These findings highlight novel and essential roles for Gαi1/3 in regulating IL-4-induced signaling, macrophage M2 polarization and allergic asthma response., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The aim of our study was to detect the expression of KIF23 in human bladder cancer tissues and to assess the potential role of KIF23 in bladder cancer progression. The expression of KIF23 and the correlation with bladder cancer patients were explored using the TCGA database. Additionally, IHC assays were also performed to detect KIF23 expression in 95 bladder cancer tissues and corresponding non-tumor tissues collected in our hospital. Colony formation, MTT, and flow cytometry (FCM) assays were performed to detect its effects on bladder cancer cell proliferation and apoptosis, respectively. An animal model was developed to found the effects of KIF23 on tumor growth in mice. Data showed that the KIF23 expression was upregulated in human bladder cancer tissues. The expression of KIF23 was correlated with the prognosis and clinicopathological features, including T stage (p=0.022) and recurrence (p=0.020), of bladder cancer patients. KIF23 depletion inhibited the proliferation of bladder cancer cells, stimulated apoptosis, and suppressed tumor growth in mice. We demonstrated the involvement of KIF23 in bladder cancer progression and provided a promising therapeutic target for the treatment of bladder cancer.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and it carries a poor prognosis. Clarifying the pathologic mechanisms of this disease will be beneficial for the diagnosis and treatment of HCC. LncRNA MEG8 is involved in several tumors but its role in HCC progression remains unknown. This study was designed to explore the role and regulatory mechanisms of MEG8 in HCC progression. MTT, EdU, wound-healing, and transwell assays were employed to analyze the proliferation, migration, and invasion of HCC cells. A luciferase assay was utilized to confirm the predicted binding site. RNA immunoprecipitation and co-immunoprecipitation were employed to verify the binding between MEG8 and miR-367-3p as well as 14-3-3ζ and TGFβR1. Real-time PCR and western blot were employed to detect the expression of interesting genes. Results revealed that MEG8 was increased in HCC tissues and cells, and was correlated with the poor prognosis of HCC patients. Inhibiting MEG8 significantly repressed the HCC cells' ability to proliferate, migrate, and invade. Moreover, MEG8 sponged miR-367-3p to upregulate 14-3-3ζ, the binding of which suppressed TGFβR1 degradation, thereby enhancing TGFβ signaling. In conclusion, this work exposed a novel role and regulatory mechanism of MEG8 in HCC and provided new insight into the treatment of HCC.

Cisplatin resistance is one of the main causes of chemotherapy failure and tumor progression in non-small cell lung cancer (NSCLC). Emodin has been demonstrated to induce NSCLC cell apoptosis and act as a potential cancer therapeutic agent. However, whether emodin could affect NSCLC cell sensitivity toward cisplatin remains unclear. The present study aimed to determine the effect of emodin and cisplatin combination on the chemosensitivity of NSCLC cells. A549 and H460 cells were treated with different concentrations of cisplatin and/or emodin. Cell Counting Kit-8, fluorescence microscopy, immunofluorescence assays and flow cytometry were used to determine cell proliferation, drug efflux, DNA damage level and cell apoptosis, respectively. P-glycoprotein (Pgp) and multidrug resistance-associated protein 1 (MRP1) expression was detected by western blotting. The results demonstrated that emodin and cisplatin inhibited the proliferation of A549 and H460 cells. Furthermore, emodin inhibited the drug efflux in A549 and H460 cells in a dose-dependent manner. In addition, emodin enhanced cisplatin-induced apoptosis and DNA damage in A549 and H460 cells. Emodin also decreased Pgp expression in A549 and H460 cells in a dose-dependent manner; however, it had no effect on MRP1 expression. Taken together, the results from the present study demonstrated that emodin can increase A549 and H460 cell sensitivity to cisplatin by inhibiting Pgp expression. Emodin may therefore be considered as an effective adjuvant for cisplatin treatment., (Copyright: © Peng et al.)

The applications of hydrogels in biomedical field has been since multiple decades. Discoveries in biology and chemistry render this platform endowed with much engineering potentials and growing continuously. Novel approaches in constructing these materials have led to the production of complex hybrid hydrogels systems that can incorporate both natural and synthetic polymers and other functional moieties for mediated cell response, tunable release kinetic profiles, thus they are used and research for diverse biomedical applications. Recent advancement in this field has established promising techniques for the development of biorelevant materials for construction of hybrid hydrogels with potential applications in the delivery of cancer therapeutics, drug discovery, and re-generative medicines. In this review, recent trends in advanced hybrid hydrogels systems incorporating nano/microstructures, their synthesis, and their potential applications in tissue engineering and anticancer drug delivery has been discussed. Examples of some new approaches including click reactions implementation, 3D printing, and photopatterning for the development of these materials has been briefly discussed. In addition, the application of biomolecules and motifs for desired outcomes, and tailoring of their transport and kinetic behavior for achieving desired outcomes in hybrid nanogels has also been reviewed., 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 Cai, Chen, Fu, Du, Yang, Mou and Hu.)

An organocatalyzed enantiodivergent synthesis of a multifunctionalized spirooxindole-norcamphor scaffold via a [4 + 2]-annulation between cyclic α, β -unsaturated ketone and methylene indolinones has been established. The presence of CaCl 2 in DMF could reverse the enantioselectivity to facilely deliver the enantiomers of the corresponding spirooxindoles. Both enantiomers of the corresponding spirooxindoles were obtained in excellent yield and diastereo-/enantioselectivity by employing one single prolinosulfonamide catalyst.

Oncolytic virotherapy (OVT) is a promising approach in cancer immunotherapy. Oncolytic viruses (OVs) could be applied in cancer immunotherapy without in-depth knowledge of tumor antigens. The capability of genetic modification makes OVs exciting therapeutic tools with a high potential for manipulation. Improving efficacy, employing immunostimulatory elements, changing the immunosuppressive tumor microenvironment (TME) to inflammatory TME, optimizing their delivery system, and increasing the safety are the main areas of OVs manipulations. Recently, the reciprocal interaction of OVs and TME has become a hot topic for investigators to enhance the efficacy of OVT with less off-target adverse events. Current investigations suggest that the main application of OVT is to provoke the antitumor immune response in the TME, which synergize the effects of other immunotherapies such as immune-checkpoint blockers and adoptive cell therapy. In this review, we focused on the effects of OVs on the TME and antitumor immune responses. Furthermore, OVT challenges, including its moderate efficiency, safety concerns, and delivery strategies, along with recent achievements to overcome challenges, are thoroughly discussed.

Dalbergia odorifera T. Chen (family Fabaceae) is one of four prized species of mahogany plant in China. In June 2017, an investigation of the condition of anthracnose was carried out on apporximately 333 hectares of D. odorifera plantations in Haikou City, Hainan Province (110.19°E, 20.03°N). Approximately 40% of D. odorifera plants had disease symptoms. Lesions on leaves were brown to grayish-white containing black dots and dark-brown borders, occasionally surrounded by a yellowish-green halo. Leaf spots generally occurred along the edge of the leaf. Severely infected leaves became withered and died. Hyphal growth was recovered from symptomatic leaf tissue, surface-sterilized with a 75% ethanol solution for 30s, rinsed with sterile distilled water, plated on potato dextrose agar (PDA), and incubated at 26°C in the dark. The representative isolate JXHTC19 was recovered by transferring a hyphal tip to a fresh PDA plate to obtain a pure culture. Fungal colonies had white aerial mycelium initially, turning pale gray after 3 days. At 7 days, colonies had a cottony appearance ranging from white to dark gray with orange masses of conidia. The colony surface was slimy and aerial mycelium was sparse. Isolates displayed single-celled, cylindrical, hyaline conidia that were rounded at both ends, and were 9.7 - 16.4 μm long (avg. 13.5 μm) × 3.6 - 6.2 μm wide (vg. 4.8 μm) (n = 100). To further identify the fungus, genomic DNA was extracted from single conidial cultures of JXHTC19. The rDNA internal transcribed spacer (ITS) region, glutamine synthetase (GS) gene, partial sequence of glyceraldeyde-3-phosphate dehydrogenase-like (GAPDH) gene, actin (ACT) gene, and beta-tubulin (TUB2) gene were amplified using the primer pairs ITS4/ITS5, GS-F/GS-R, GDF1/GDR1, ACT-512F/ACT-783R, and TUB2-T1/Bt-2b (Weir et al 2012), respectively. The results showed that the ITS, GS, GAPDH, ACT and TUB2 genes of the target strain (JXHTC19) have 100%, 95%, 100%, 97% and 98% sequence homology with C. brevisporum, respectively. The sequences obtained were deposited in GenBank (MF993572, MN737615, MN737614, MG515612, and MG515615[LJ1]). All five sequences were analyzed together with representative sequences from type or ex-type specimens of the Colletotrichum genus (Yang et al. 2011, Weir et al. 2012) and a phylogenetic tree was generated via the neighbor-joining method using MEGA6. The tree placed the isolate in the same group as C. brevisporum. Thus, both morphological and molecular characteristics identified the pathogen as C. brevisporum. To verify Koch's postulates, two-year-old leaves of healthy potted D. odorifera plants (n = 6) were inoculated with a spore suspensions of JXHTC19 that contained 105 conidia/ml. Plants were sprayed with water to serve as mock-inoculated controls [LJ2](Garibaldi et al, 2020). Six plants per treatment were used in each test. The test was repeated once.Plants were incubated in moist chambers at 26°C and monitored daily for symptom development. After five days, eleven of twelve isolates [LJ3]caused lesions on all inoculated plants, whereas no symptoms developed on the mock-inoculated controls. Koch's postulates were fulfilled by reisolating the same fungus and verifying its colony and morphological characters as C. brevisporum. To our knowledge, this is the first report of this species causing anthracnose of D. odorifera in China. Corresponding measures must be adopted to manage this disease such as reducing the planting density of D. odorifera and increasing the species diversity of undergrowth vegetation. These results could help develop better monitoring and management practices for this disease.

The macrophage-related immune response is an important component of the cochlear response to different exogenous stresses, including noise, ototoxic antibiotics, toxins, or viral infection. However, the role of the immune response in hereditary deafness caused by genetic mutations is rarely explored. GJB2 , encoding connexin 26 (Cx26), is the most common deafness gene of hereditary deafness. In this study, two distinct Cx26-null mouse models were established to investigate the types and underlying mechanisms of immune responses. In a systemic Cx26-null model, macrophage recruitment was observed, associated with extensive cell degeneration of the cochlear epithelium. In a targeted-cell Cx26-null model, knockout of Cx26 was restricted to specific supporting cells (SCs), which led to preferential loss of local outer hair cells (OHCs). This local OHC loss can also induce a macrophage-related immune response. Common inflammatory factors, including TNF-α, IL-1β, Icam-1, Mif, Cx3cr1, Tlr4, Ccl2, and Ccr2, did not change significantly, while mRNA of Cx3cl1 was upregulated. Quantitative immunofluorescence showed that the protein expression of CX3CL1 in Deiters cells, a type of SC coupled with OHCs, increased significantly after OHC death. OHC loss caused the secondary death of spiral ganglion neurons (SGNs), while the remaining SGNs expressed high levels of CX3CL1 with infiltrated macrophages. Taken together, our results indicate that CX3CL1 signaling regulates macrophage recruitment and that enhancement of macrophage antigen-presenting function is associated with cell degeneration in Cx26-null mice., 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 Xu, Chen, Xie, Qiu, Bai, Liu, Zhang, Wang, Jin, Sun and Kong.)

Background: Renal cell carcinoma (RCC) is a clinically common tumor in the urinary system, showing an upward trend of both incidence and mortality. Apolipoprotein C1 (APOC1) has been identified as a vital regulator in tumor progression. This study aims to uncover the biological function of APOC1 in RCC process and the underlying mechanism., Methods: Differential levels of APOC1 in RCC samples and normal tissues in a downloaded TCGA profile and clinical samples collected in our center were detected by quantitative reverse transcription PCR (qRT-PCR). The prognostic value of APOC1 in RCC was assessed by depicting Kaplan-Meier survival curves. After intervening APOC1 level by transfection of sh-APOC1 or oe-APOC1, changes in phenotypes of RCC cells were examined through CCK-8, colony formation, Transwell assay and flow cytometry. Subsequently, protein levels of EMT-related genes influenced by APOC1 were determined by Western blot. The involvement of the Wnt3a signaling in APOC1-regulated malignant process of RCC was then examined through a series of rescue experiments. Finally, a RCC xenograft model was generated in nude mice, aiming to further clarify the in vivo function of APOC1 in RCC process., Results: APOC1 was upregulated in RCC samples. Notably, its level was correlated to overall survival of RCC patients, displaying a certain prognostic value. APOC1 was able to stimulate proliferative, migratory and invasive abilities in RCC cells. The Wnt3a signaling was identified to be involved in APOC1-mediated RCC process. Notably, Wnt3a was able to reverse the regulatory effects of APOC1 on RCC cell phenotypes. In vivo knockdown of APOC1 in xenografted nude mice slowed down the growth of RCC., Conclusions: APOC1 stimulates the malignant process of RCC via targeting the Wnt3a signaling.

Aims: Lysine acetyltransferase 6B (KAT6B), is a histone acetyltransferase implicated to have a role in tumor suppression. However, the relationship between KAT6B and hepatocellular carcinoma (HCC) is unclear. The purpose of this study was to detect the expression of KAT6B in HCC tissues and analyze its connection with the clinicopathological features of HCC., Methods: First, we performed immunohistochemical staining on 250 HCC tissues and 222 non-tumor liver tissues to examine the expression of KAT6B.Then the relation between KAT6B expression and clinicopathological parameters was analyzed by chi-square test, and the overall survival analysis was conducted by Kaplan-Meier survival method. In addition, based on the Oncomine expression array online and the UALCAN database, we compared KAT6B expression differences between normal liver tissues and HCC tissues more broadly., Results: Compared with normal tissues, KAT6B expression was significantly lower in HCC tissues. Low KAT6B expression was found to be related to gender, AFP level, and tumor size. According to the online database, KAT6B expression was found to be decreased in HCC tissues and high in normal tissues., Conclusions: Lower expression of KAT6B is associated with poor prognosis of HCC, and KAT6B may be a potential tumor suppressor in liver cancer.

To evaluate the safety of ivermectin microemulsion injection, 100 Wistar rats were injected intraperitoneally at 0.38 g/kg, 0.19 g/kg, and 0.1 g/kg for 14 days. The 14-day repeated toxicity test of ivermectin microemulsion injection was systematically evaluated by clinical observation, organ coefficient, hematological examination, clinical chemistry examination, and histopathological examination. The results showed that no rats died during the test. At the initial stage of treatment, the rats in the high dose group had mild clinical reaction, which disappeared after 4 days. Clinical chemistry showed that the high dose of ivermectin microemulsion could cause significant changes in ALT and LDH parameters in male rats; high and medium doses could increase the liver coefficients of male and female rats. The toxic target organ may be the liver as indicated by histopathological findings. No significant toxic injury was found in the heart, liver, spleen, lung, kidney, brain, ovary, and testes of all groups of rats. No drug-related toxic effects were found at low doses, and thus the NOVEL of ivermectin microemulsion injection was 0.19 g/kg., Competing Interests: S-yX was employed by the company China Agricultural Vet. Bio. Biomedical Co., Ltd. The remaining 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 © 2020 Dong, Xing, Zhang and Zhou.)

The chloride diffusivity of concrete is an important parameter for assessing the long-term durability of coastal concrete structures. The purpose of this paper is to present a three-dimensional random walk algorithm (RWA) for estimating the chloride diffusivity of concrete. By analyzing the size distribution of aggregates, the equivalent interfacial transition zone (ITZ) thickness is derived in an analytical manner. Each aggregate is combined with the surrounding ITZ to construct an equivalent aggregate model (EAM) and the chloride diffusivity is formulated. It is found that the equivalent ITZ thickness decreases with the increase of practical ITZ thickness and aggregate volume fraction. The aggregate gradation influences the equivalent ITZ thickness to a certain extent. The relative chloride diffusivity of the equivalent aggregate is almost directly and inversely proportional to the equivalent ITZ thickness and the aggregate radius, respectively. The numerical results show that, when the EAM is adopted, the computational time is greatly reduced. With the EAM, concrete can be modeled as a two-phase material and the chloride diffusivity is estimated by applying the RWA. It is shown that, with the increase of mean square displacement and number of Brownian particles, the average chloride diffusivity of concrete approaches a stable value. Finally, through comparison with experimental data, the validation of the RWA is preliminarily verified.

Background: Autosomal recessive cutis laxa type IC (ARCL IC, MIM: #613177) results from a mutation in the LTBP4 gene (MIM: #604710) on chromosome 19q13., Case Presentation: A 28-day-old Chinese infant with generalized cutis laxa accompanied by impaired pulmonary, gastrointestinal, genitourinary, retinal hemorrhage, abnormality of coagulation and hyperbilirubinemia was admitted to our hospital. To find out the possible causes of these symptoms, whole-exome sequencing was performed on the infant. Two novel pathogenic frame-shift variants [c.605&#95;606delGT (p.Ser204fs * 8) and c.1719delC (p.Arg574fs * 199)] of the LTBP4 gene associated with ARCL IC were found which was later verified by Sanger sequencing. The pathogenicity of mutations was subsequently assessed by several software programs and databases. In addition, an analytical review on the clinical phenotypes of the disease previously reported in literature was performed., Conclusions: This is the first report of a Chinese infant with ARCL IC in China due to novel pathogenic variations of LTBP4. Our study extends the cutis laxa type IC mutation spectrum as well as the phenotypes associated with the disease in different populations.

High-polluting industries are regarded as the main sources of air pollutant emissions and the major factors that significantly destroy the ecological environment. Corporate innovation in high-polluting industries improves the energy consumption efficiency and reduces the emission of air pollutant, which mitigates the conflict between environment and economy. Using the sample of China's listed firms from 2010 to 2017, this study examines the impact of corporate social responsibility (CSR) and financialization on corporate innovation in high-polluting industries. The results show that there is a positive association between CSR and corporate innovation, while there is a negative association between financialization and corporate innovation. Furthermore, the financialization of high-polluting firms can alleviate the promotion role of CSR in the innovation process. The financialization of state-owned enterprises in high-polluting industries may not have a crowding-out effect on research and development (R&D), but it can limit the R&D promotion effect of CSR engagements. In contrast, the financialization of non-state-owned enterprises will hinder corporate innovation, but it will not affect the association between CSR and technology innovation. We also find that the financialization of high-polluting firms with low financial constraints can alleviate the promotion role of CSR engagements in innovation. Meanwhile, the CSR engagements of high-polluting firms with high financial constraints play a stronger role in corporate innovation. During the implementation of environmental policies, the negative association between financialization and corporate innovation has been strengthened. Our findings can encourage high-polluting firms to make more efforts in environmental protection and social stability.

Context: Curcumin has shown efficacy in promoting radiosensitivity combined with radiotherapy. However, the role and mechanism of curcumin on radiosensitivity in laryngeal squamous cell cancer (LSCC) is largely unknown. Objective: The aim of our study is to explore the role of IKKγ-NF-κB signaling in curcumin enhancing LSCC cell radiosensitivity in vitro . Materials and methods: Curcumin and X-ray were used to induce cell DNA damage and apoptosis, or inhibit cell clone formation. IKKγ siRNA and plasmid were used to change IKKγ expression. The CCK8 assay was used to detect cell viability. Clone formation ability was analyzed using a clonogenic assay, cell apoptosis was examined using flow cytometry, an immunofluorescence assay was used to detect DNA damage, while mRNA and protein levels were assayed using real time PCR and western blotting, respectively. Results: Curcumin significantly enhanced irradiation-induced DNA damage and apoptosis, while weakening clone-forming abilities of LSCC cell line Hep2 and Hep2-max. Compared to Hep2 cells, Hep2-max cells are more sensitive to curcumin post-irradiation. Curcumin suppressed irradiation-induced NF-κB activation by suppressing IKKγ expression, but not IKKα and IKKβ. Overexpression of IKKγ decreased irradiation-induced DNA damage and apoptosis, while promoting clone-forming abilities of Hep2 and Hep2-max cells. IKKγ overexpression further increased expression of NF-κB downstream genes, Bcl-XL, Bcl-2, and cyclin D1. Conversely, IKKγ silencing enhanced irradiation-induced DNA damage and apoptosis, but promoted clone formation in Hep2 and Hep2-max cells. Additionally, IKKγ silencing inhibited expression of Bcl-XL, Bcl-2, and cyclin D1. Conclusions: Curcumin enhances LSCC radiosensitivity via NF-ΚB inhibition by suppressing IKKγ expression.

Background: IgA nephropathy (IgAN) is one of the most common forms of primary glomerulonephritis. Recent studies have indicated that small noncoding RNAs, such as tRNA-derived small RNAs (tsRNAs), might be novel biomarkers for glomerulonephritis. We therefore investigated the potential roles and possible functions of the tsRNAs in IgAN., Method: Peripheral blood mononuclear cells (PBMCs) were extracted from blood samples of the patients with IgAN and healthy control groups. The expression profiles of tsRNAs were assessed by small RNA sequencing (RNA-Seq) in PBMCs of the IgAN and control groups. Dysregulated tsRNAs were selected for validation by quantitative real-time polymerase chain reaction (qRT-PCR). Target gene prediction and enrichment were performed by bioinformatics analysis., Results: The results revealed that 143 significantly upregulated and 202 significantly downregulated tsRNAs were differentially altered in the IgAN group compared with the control group. Five upregulated tsRNAs (tRF-Val-AAC-007, tRF-Ala-AGC-063, tRF-Gln-CTG-010, tRF-Tyr-GTA-011 and tRF-Thr-AGT-007) and 3 downregulated tsRNAs (tiRNA-Val-TAC-004, tRF-Gly-CCC-005 and tRF-His-GTG-006) were selected for validation by qRT-PCR; the results were consistent with the sequencing data. Gene Ontology (GO) analysis revealed that the target genes predicted by upregulated tsRNAs were mostly enriched in "nucleic acid metabolic process,' "intracellular part,' and "ion binding,' whereas the target genes predicted by downregulated tsRNAs were mostly enriched in "regulation of cellular component organization,' "membrane-bound organelle,' and "ion binding.' Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the target genes predicted by upregulated tsRNAs were mostly enriched in "herpes simplex virus 1 infection,' whereas the target genes predicted by downregulated tsRNAs were mostly enriched in "circadian rhythm CONCLUSIONS:: The present study confirmed the differential expression of tsRNAs in patients with IgAN, and these dysregulated tsRNAs might be novel potential targets for the diagnosis and treatment of IgAN.