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The construction of "zero-free cities" is an effective plan to achieve the carbon peak plan, reduce pollution and carbon emissions, and promote a circular economy. Based on the WARM model and Emission factor method, the total carbon emission reduction of solid waste sources and disposal in each field during the implementation of the zero-free city policy in Chongqing （2017-2021） was calculated, and the total carbon emission reduction of solid waste in each field in 2025 was predicted by scenario. The results showed that： ① After the implementation of cleaner production and green manufacturing policies in Chongqing, the generation intensity of general industrial solid waste decreased to 0.20 t·（10 4 yuan） -1 in 2021, and the carbon emission reduction in the industrial sector had been increasing since 2020. Due to the growth of the economy and living level, the per capita production of food waste, domestic waste, and e-waste increased, failing to reduce emissions at the source in these areas. In addition, the promotion of green food and organic agricultural products and the restriction of the use of chemical fertilizers and pesticides could be strengthened to further reduce source emissions in the agricultural field. ② General industrial solid waste, construction waste, and straw were the key areas to achieve carbon emission reduction, and their carbon emission reductions were predicted to increase to 2 796.64×10 4 , 538.54×10 4 , and 99.07×10 4 t in 2021. Respectively, reducing the landfill volume in the above fields is the key to emission reduction. In the field of daily life, the collection and transportation of solid waste should be improved, the sorting process and disposal facilities should be refined, and the resource recycling rate should be improved to reduce its carbon emissions. Due to the improvement of the collection level and the application of straw feed and fertilizer, the carbon emission reduction of straw and agricultural film is generally rising, and the proportion of straw and livestock manure directly returned to the field should be reduced in the agricultural field, and the allocation of biomass disposal facilities to promote the co-disposal of the two may be the best means of carbon emission reduction. ③ In 2025, the predicted carbon emission reductions in Chongqing under the BAU scenario and the PLAN scenario were 2 289.78×10 4 and 2 750.31×10 4 t, respectively, indicating that the upgrading and transformation of local industries and the large-scale scale of the renewable resources industry have achieved good carbon reduction benefits. With the construction and improvement of various waste disposal facilities in 2025, the carbon emission reduction of the solid waste disposal process in various fields will continue to increase, but the carbon emissions of hazardous waste, municipal sludge, and livestock and poultry manure will still be in a state of growth due to the possible increase in total output in the future.

Background: In arrhythmogenic cardiomyopathy (ACM), left ventricle-dominant presentation has poorer outcomes than right-dominant presentation, suggesting that interventricular functional disparity might play a role in patients' prognosis. However, the prognostic impact of ventricular functional discordance in ACM patients remains unknown., Purpose: To assess whether ventricular functional disparity measured as ventricular discordance index, defined as the ratio of right-ventricular ejection fraction (RVEF) to left-ventricular ejection fraction (LVEF), might reveal prognostic disparities between phenotypes and offer added risk stratification value., Study Type: Retrospective., Subjects: A total of 222 patients with ACM (mean age 44 ± 16 years, 144 males) from three centers were included., Field Strength/sequence: 3-T, cine imaging., Assessment: Ventricular discordance index was calculated using cine-derived RVEF and LVEF, for which a threshold was determined using Youden J index. Clinically ventricular discordance was defined as ventricular discordance index above the threshold. The major adverse cardiac events (MACE), was defined as sudden cardiac death, appropriate implantable cardioverter-defibrillator intervention, and aborted cardiac arrest. International task diagnostic force criteria and the 5-year risk score were evaluated., Statistical Tests: The prognostic implications of ventricular discordance index and clinically ventricular discordance were evaluated using multivariable Cox analysis. P < 0.05 indicated the statistical significance., Results: During a median follow-up of 50 months, 81 (37%) patients experienced MACE. The ventricular discordance index was independently associated with MACE (hazard ratio [HR]: 1.49; 95% confidence interval [CI]: 1.23-1.82). Patients classified under clinically ventricular discordance experienced higher MACE rates and were less likely to meet the task force structural criteria. clinically ventricular discordance was independently associated with MACE (adjusted HR: 2.2; 95% CI: 1.36-3.55). Clinically ventricular discordance, LV involvement and the 5-year risk score in combined reclassified 20.3% of patients compared to 2015 task force classification., Data Conclusion: Ventricular discordance was associated with MACE in ACM, potentially providing prognostic value beyond the 5-year risk score., Level of Evidence: 3 TECHNICAL EFFICACY: 5., (© 2024 International Society for Magnetic Resonance in Medicine.)

Extracellular membrane proteins are crucial for mediating cell attachment, recognition, and signal transduction in the testicular microenvironment, particularly germline stem cells. Cadherin 18 (CDH18), a type II classical cadherin, is primarily expressed in the nervous and reproductive systems. Here, we investigated the expression of CDH18 in neonatal porcine prospermatogonia (ProSGs) and murine spermatogonial stem cells (SSCs). Disruption of CDH18 expression did not adversely affect cell morphology, proliferation, self-renewal, or differentiation in cultured porcine ProSGs, but enhanced cell adhesion and prolonged cell maintenance. Transcriptomic analysis indicated that the down-regulation of CDH18 in ProSGs significantly up-regulated genes and signaling pathways associated with cell adhesion. To further elucidate the function of CDH18 in germ cells, Cdh18 knockout mice were generated, which exhibited normal testicular morphology, histology, and spermatogenesis. Transcriptomic analysis showed increased expression of genes associated with adhesion, consistent with the observations in porcine ProSGs. The interaction of CDH18 with β-catenin and JAK2 in both porcine ProSGs and murine SSCs suggested an inhibitory effect on the canonical Wnt and JAK-STAT signaling pathways during CDH18 deficiency. Collectively, these findings highlight the crucial role of CDH18 in regulating cell adhesion in porcine ProSGs and mouse SSCs. Understanding this regulatory mechanism provides significant insights into the testicular niche.

Background: The prognostic value of left ventricular (LV) myocardial trabecular complexity on cardiovascular magnetic resonance (CMR) in dilated cardiomyopathy (DCM) remains unknown. This study aimed to evaluate the prognostic value of LV myocardial trabecular complexity using fractal analysis in patients with DCM., Methods: Consecutive patients with DCM who underwent CMR between March 2017 and November 2021 at two hospitals were prospectively enrolled. The primary endpoints were defined as the combination of all-cause death and heart failure hospitalization. The events of cardiac death alone were defined as the secondary endpoints.LV trabeculae complexity was quantified by measuring the fractal dimension (FD) of the endocardial border based on fractal geometry on CMR. Cox proportional hazards regression and Kaplan-Meier survival analysis were used to examine the association between variables and outcomes. The incremental prognostic value of FD was assessed in nested models., Results: A total of 403 patients with DCM (49.31 ± 14.68 years, 69% male) were recruited. After a median follow-up of 43 months (interquartile range, 28-55 months), 87 and 24 patients reached the primary and secondary endpoints, respectively. Age, heart rate, New York Heart Association functional class >II, N-terminal pro-B-type natriuretic peptide, LV ejection fraction, LV end-diastolic volume index, LV end-systolic volume index, LV mass index, presence of late gadolinium enhancement, global FD, LV mean apical FD, and LV maximal apical FD were univariably associated with the outcomes (all P < 0.05). After multivariate adjustment, LV maximal apical FD remained a significant independent predictor of outcome [hazard ratio = 1.179 (1.116, 1.246), P < 0.001]. The addition of LV maximal apical FD in the nested models added incremental prognostic value to other common clinical and imaging risk factors (all <0.001; C-statistic: 0.84-0.88, P < 0.001)., Conclusion: LV maximal apical FD was an independent predictor of the adverse clinical outcomes in patients with DCM and provided incremental prognostic value over conventional clinical and imaging risk factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Safely expanding indications for cellular therapies has been challenging given a lack of highly cancer-specific surface markers. Here we explore the hypothesis that tumor cells express cancer-specific surface protein conformations that are invisible to standard target discovery pipelines evaluating gene or protein expression, and these conformations can be identified and immunotherapeutically targeted. We term this strategy integrating cross-linking mass spectrometry with glycoprotein surface capture 'structural surfaceomics'. As a proof of principle, we apply this technology to acute myeloid leukemia (AML), a hematologic malignancy with dismal outcomes and no known optimal immunotherapy target. We identify the activated conformation of integrin β 2 as a structurally defined, widely expressed AML-specific target. We develop and characterize recombinant antibodies to this protein conformation and show that chimeric antigen receptor T cells eliminate AML cells and patient-derived xenografts without notable toxicity toward normal hematopoietic cells. Our findings validate an AML conformation-specific target antigen and demonstrate a tool kit for applying these strategies more broadly., (© 2023. The Author(s).)

Purpose: To evaluate the feasibility of using mpMRI image features predicted by AI algorithms in the prediction of clinically significant prostate cancer (csPCa)., Materials and Methods: This study analyzed patients who underwent prostate mpMRI and radical prostatectomy (RP) at the Affiliated Hospital of Jiaxing University between November 2017 and December 2022. The clinical data collected included age, serum prostate-specific antigen (PSA), and biopsy pathology. The reference standard was the prostatectomy pathology, and a Gleason Score (GS) of 3 + 3 = 6 was considered non-clinically significant prostate cancer (non-csPCa), while a GS ≥ 3 + 4 was considered csPCa. A pre-trained AI algorithm was used to extract the lesion on mpMRI, and the image features of the lesion and the prostate gland were analyzed. Two logistic regression models were developed to predict csPCa: an MR model and a combined model. The MR model used age, PSA, PSA density (PSAD), and the AI-predicted MR image features as predictor variables. The combined model used biopsy pathology and the aforementioned variables as predictor variables. The model's effectiveness was evaluated by comparing it to biopsy pathology using the area under the curve (AUC) of receiver operation characteristic (ROC) analysis., Results: A total of 315 eligible patients were enrolled with an average age of 70.8 ± 5.9. Based on RP pathology, 18 had non-csPCa, and 297 had csPCa. PSA, PSAD, biopsy pathology, and ADC value of the prostate outside the lesion (ADC prostate ) varied significantly across different ISUP grade groups of RP pathology (P < 0.001). Other clinical variables and image features did not vary significantly across different ISUP grade groups (P > 0.05). The MR model included PSAD, the ratio of ADC value between the lesion and the prostate outside the lesion (ADC lesion/prostate ), the signal intensity ratio of DWI between the lesion and the prostate outside the lesion (DWI lesion/prostate ), and the ratio of DWI lesion/prostate to ADC lesion/prostate . The combined model included biopsy pathology, ADC lesion/prostate , mean signal intensity of the lesion on DWI (DWI lesion ), DWI signal intensity of the prostate outside the lesion (DWI prostate ), and signal intensity ratio of DWI between the lesion and the prostate outside the lesion (DWI lesion/prostate ). The AUC of the MR model (0.830, 95% CI 0.743, 0.916) was not significantly different from that of biopsy pathology (0.820, 95% CI 0.728, 0.912, P = 0.884). The AUC of the combined model (0.915, 95% CI 0.849, 0.980) was higher than that of the biopsy pathology (P = 0.042) and MR model (P = 0.031)., Conclusion: The aggressiveness of prostate cancer can be effectively predicted using AI-extracted image features from mpMRI images, similar to biopsy pathology. The prediction accuracy was improved by combining the AI-extracted mpMRI image features with biopsy pathology, surpassing the performance of biopsy pathology alone., (© 2023. The Author(s).)

Precise targeting of large transgenes to T cells using homology-directed repair has been transformative for adoptive cell therapies and T cell biology. Delivery of DNA templates via adeno-associated virus (AAV) has greatly improved knockin efficiencies, but the tropism of current AAV serotypes restricts their use to human T cells employed in immunodeficient mouse models. To enable targeted knockins in murine T cells, we evolved Ark313, a synthetic AAV that exhibits high transduction efficiency in murine T cells. We performed a genome-wide knockout screen and identified QA2 as an essential factor for Ark313 infection. We demonstrate that Ark313 can be used for nucleofection-free DNA delivery, CRISPR-Cas9-mediated knockouts, and targeted integration of large transgenes. Ark313 enables preclinical modeling of Trac-targeted CAR-T and transgenic TCR-T cells in immunocompetent models. Efficient gene targeting in murine T cells holds great potential for improved cell therapies and opens avenues in experimental T cell immunology., Competing Interests: Declaration of interests J.A., W.A.N., J.E., and A.A. are co-inventors on a patent application filed on the subject matter of this study. A.A. is a cofounder and board member at StrideBio and TorqueBio. J.E. is a compensated co-founder at Mnemo Therapeutics and a compensated scientific advisor to Cytovia Therapeutics. J.E. owns stocks in Mnemo Therapeutics and Cytovia Therapeutics. J.E. has received a consulting fee from Casdin Capital, Resolution Therapeutics and Treefrog Therapeutics. The J.E. lab has received research support from Cytovia Therapeutics, Mnemo Therapeutics, and Takeda Pharmaceutical Company., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Capturing CO 2 and subsequently converting into valuable chemicals has attracted extensive attention. Herein, a series of biomass-based N-rich porous carbon materials with high specific surface area and pore volume were prepared using biomass waste soybean dregs as precursors. The nitrogen content was up to 4 % with different forms in the carbon skeleton such as pyridine-N, pyrrole-N. The synergistic effect of ultra-micropore (pore size <0.7 nm) and N-containing groups endowed the materials with a high CO 2 adsorption capacity, reaching 6.3 and 3.6 mmol g -1 at 0 and 25 °C under atmospheric pressure, respectively. In addition, the sufficient interaction between N-containing groups and CO 2 was demonstrated by solid-state nuclear magnetic resonance spectroscopy, and the captured CO 2 was possibly activated in the form of carbamate, which is conducive to subsequent conversion. Therefore, the supported catalyst with the as-synthetic porous carbon material as the carrier and Zn II as catalytic sites was prepared and successfully applied for carboxylative cyclization of propargylic amine with CO 2 to afford the 3-benzyl-5-methyleneoxazolidin-2-one. The results showed that CO 2 capture and in-situ conversion work effectively to produce highly value-added chemicals. In this process, the captured CO 2 could be activated and fixed into chemicals in mild conditions. More importantly, the energy consumption in CO 2 desorption and adsorbent regeneration could be avoided. The valorization of both solid waste and CO 2 to valuable chemicals provides an elegant strategy of killing three birds with one stone., (© 2022 Wiley-VCH GmbH.)

Background: There is no remedial strategy other than definitive chemoradiotherapy for patients with advanced esophageal squamous cell carcinoma (ESCC) who are not eligible to undergo surgical treatment., Aim: To introduce a novel therapy called endoscopic debulking resection (EdR) followed by additive chemoradiotherapy (CRT) and evaluate its efficacy and safety., Methods: Advanced, inoperable ESCC patients between 1 January 2015 and 30 December 2019 were investigated retrospectively. Patients who received EdR followed by CRT were deemed the EdR + CRT group and those without CRT were deemed the EdR group. Overall survival (OS), progression-free survival (PFS), and adverse events were evaluated., Results: A total of 41 patients were enrolled. At a median follow-up of 36 mo (range: 1-83), the estimated 1-, 2-, and 3-year cumulative OS rates of patients who underwent EdR plus additive CRT were 92.6%, 85.2%, and 79.5%, respectively, which were higher than those of patients who underwent EdR alone (1-year OS, 83.3%; 2-year OS, 58.3%; 3-year OS, 50%; P = 0.05). The estimated 2-year cumulative PFS rate after EdR + CRT was 85.7%, while it was 61.5% after EdR ( P = 0.043). According to the univariate and multivariate Cox regression analyses, early clinical stage (stage ≤ IIB) and additive CRT were potential protective factors for cumulative OS. No severe adverse events were observed during the EdR procedure, and only mild to moderate myelosuppression and radiation pneumonia were observed in patients who underwent additive CRT after EdR., Conclusion: EdR plus CRT is an alternative strategy for selective advanced inoperable ESCC patients., Competing Interests: Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: To evaluate the effects of manganese superoxide dismutase (Mn-SOD) from thermophilic bacterium HB27 (name as Tt-SOD) on chemical cystitis., Methods: Control and experimental rats were infused by intravesical saline or hydrochloric acid (HCl) on the first day of the experiments. Saline, sodium hyaluronate (SH) or Tt-SOD were infused intravesically once a day for three consequent days. On the fifth day, the rats were weighted and sacrificed following a pain threshold test. The bladder was harvested for histological and biochemical analyses., Results: Tt-SOD could reduce the bladder index, infiltration of inflammatory cells in tissues, serum inflammatory factors and SOD levels, mRNA expression of inflammatory factors in tissues, and increase perineal mechanical pain threshold and serum MDA and ROS levels in HCl-induced chemical cystitis. Furthermore, Tt-SOD alleviated inflammation and oxidative stress by the negative regulation of the NF-κB p65 and p38 MAPK signaling pathway., Conclusions: Intravesical instillation of Tt-SOD provides protective effects against HCl-induced cystitis., (© 2021. The Author(s).)

Purpose: This study aimed at exploring the feasibility and reproducibility of CCT for the measurement of Left Atrial (LA) strain and volume compared with transthoracic echocardiography (TTE) in pediatric patients with congenital heart disease (CHD)., Materials and Methods: The present study included 43 postoperative patients with CHD (7.39 ± 3.64 years, 56% male) who underwent clinically indicated CCT, and all patients underwent additional TTE on the same day. LA strain and volume parameters were measured by dedicated software. The correlation and agreement of LA strain and volume parameters were assessed using Pearson's correlation coefficient and Bland-Altman analysis. Intra-class correlation coefficients (ICC) were used to assess CCT intra-observer and inter-observer reproducibility., Results: All strain parameters of CCT were lower compared to TTE (reservoir strain: 28.37 ± 6.92 vs. 32.15 ± 8.15, respectively; conduit strain: 21.33 ± 6.46 vs. 24.23 ± 7.75, respectively; booster strain: 7.04 ± 2.74 vs. 7.92 ± 3.56). While the volume parameters of CCT were higher compared to TTE (LAV: 29.60 ± 19.01 vs. 25.66 ± 17.60, respectively; LAVi: 30.36 ± 22.31 vs. 28.63 ± 19.25, respectively). Both LA strain and volume measurements showed good correlation and agreement between the two modalities ( r = 0.63-0.87, p < 0.001). CT-derived LA strain and volume measurements showed good intra- and inter-observer reproducibility using prototype software ( ICC = 0.78-0.96)., Conclusions: CCT was feasible for measuring LA strain and volume with good correlation and high reproducibility as compared with TTE. As a complementary modality, CCT can regard as an accepted method in the evaluation of LA function in pediatric patients with CHD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xie, Chen, Hu, Ouyang, Guo, Sun, Wang, Qiu, Zhang, Zhang, Fu and Zhong.)

Background: Vortex formation time (VFT) had been considered a useful marker for assessing diastolic performance. the VFT assessment of diastolic function using four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) has not been used in repair of tetralogy of Fallot (rTOF) patient. The aims of this study were as follows: (I) establish reference ranges for VFT measurements in healthy children and adolescents using 4D flow CMR imaging; and (II) analyze VFT parameters to assess diastole dysfunction in rTOF patients group., Methods: We acquired the CMR data was of 62 healthy participants (aged 6-18 years; male: 40, female: 22) and 20 patients with rTOF (aged 10-13 years; male: 15, female: 5) using 4D flow and cine sequence in routine chamber view. The VFT was calculated based on comparison of different algorithms from cine measurements (VFT volume ) and 4D flow measurements (VFT blood ). Then, VFT measurements were compared to subject peak filling rate (PFR), age, and cardiac mass using simple linear regression and multiple regression analyses. Data were also categorized according to age for VFT and cardiac functional assessment comparisons between 3 age groups (Group 1: 6-9 years; Group 2: 10-13 years; Group 3: 14-18 years). The correlation of VFT and cardiac function parameters were analyzed in the rTOF group., Results: Normal mean value of VFT volume and VFT blood were 4.25±0.92 and 3.77±1.11 in healthy children participants. The VFT volume was correlated with VFT blood (r=0.61, P<0.001). There was a moderately significant correlation between VFT volume and PFR (r=0.46, P<0.001) and between VFT blood and PFR (r=0.47, P<0.001), age (r=0.41, P=0.002) and left ventricular (LV) mass (r=0.48, P<0.001). Multiple regression analyses demonstrated that VFT volume was independently associated with PFR (T=2.239; P<0.05) and VFT blood (T=4.361; P<0.001). There was a significant difference in VFT volume between healthy controls and rTOF patients (5.44±1.93 vs. 4.27±0.88, P=0.018)., Conclusions: The VFT measurements showed that the LV that had appropriate space to form the optimal vortex ring in normal children and adolescents aged 6-18 years old. The VFT volume could potentially be helpful in improving our understanding of LV diastolic dysfunction in rTOF patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-22-67/coif). All authors report technical assistance from Gaston Vogel and Qiuchen Wang (Pie Medical Imaging Corporation Netherlands), and statistical assistance from Tingfan Wu (GE Healthcare). The authors have no other conflicts of interest to declare., (2022 Translational Pediatrics. All rights reserved.)

We investigated the therapeutic effects of superoxide dismutase (SOD) from thermophilic bacterium HB27 on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and its underlying mechanisms. A Sprague-Dawley rat model of CP/CPPS was prepared and then administered saline or Thermus thermophilic (Tt)-SOD intragastrically for 4 weeks. Prostate inflammation and fibrosis were analyzed by hematoxylin and eosin staining, and Masson staining. Alanine transaminase (ALT), aspartate transaminase (AST), serum creatinine (CR), and blood urea nitrogen (BUN) levels were assayed for all animals. Enzyme-linked immunosorbent assays (ELISA) were performed to analyze serum cytokine concentrations and tissue levels of malondialdehyde, nitric oxide, SOD, catalase, and glutathione peroxidase. Reactive oxygen species levels were detected using dichlorofluorescein diacetate. The messenger ribonucleic acid (mRNA) expression of tissue cytokines was analyzed by reverse transcription polymerase chain reaction (RT-PCR), and infiltrating inflammatory cells were examined using immunohistochemistry. Nuclear factor-κB (NF-κB) P65, P38, and inhibitor of nuclear factor-κBα (I-κBα) protein levels were determined using western blot. Tt-SOD significantly improved histopathological changes in CP/CPPS, reduced inflammatory cell infiltration and fibrosis, increased pain threshold, and reduced the prostate index. Tt-SOD treatment showed no significant effect on ALT, AST, CR, or BUN levels. Furthermore, Tt-SOD reduced inflammatory cytokine expression in prostate tissue and increased antioxidant capacity. This anti-inflammatory activity correlated with decreases in the abundance of cluster of differentiation 3 (CD3), cluster of differentiation 45 (CD45), and macrophage inflammatory protein 1α (MIP1α) cells. Tt-SOD alleviated inflammation and oxidative stress by reducing NF-κB P65 and P38 protein levels and increasing I-κBα protein levels. These findings support Tt-SOD as a potential drug for CP/CPPS., Competing Interests: None

A hybrid photocatalytic assembly with Ni poly-pyridine polymers binding on CdS quantum dots was developed via thiophene immobilization. The fabricated hybrid assembly facilitated efficient charge separation, and each component endowed great synergy. As a result, a high syngas production rate was achieved over 5500 μmol g cat -1  h -1 from photocatalytic CO 2 reduction under visible-light irradiation, accompanied by an adjustable H 2 /CO ratio ranging from 4 : 1 to 1 : 3. A novel hybrid assembly was described for syngas synthesis with boosted activity and controlled selectivity, which provides a profile to ingeniously understand molecular-level design for photocatalysts., (© 2022 Wiley-VCH GmbH.)

Background: Anal squamous cell carcinoma (ASCC) is a rare malignant tumor with increasing incidence. The goal of our study was to analyze the treatment outcome and prognostic factors of ASCC in South China in the past half-century., Methods: This study retrospectively included 59 patients with ASCC admitted from 1975 to 2018 in Sun Yat-sen University cancer center. The clinical records and follow-up information of all patients were collected. Survival analysis and univariate and multivariate regression analyses were performed using the "survival" and "survminer" packages of R software., Results: In 59 patients, 5 patients had distant metastasis at diagnosis. Among 54 M0 stage patients, 33 patients received chemoradiotherapy (CRT), 19 patients received local surgery, and 2 patients refused curative treatment and received the best supportive treatment (BST). The most common grade 3-4 acute toxicities during treatment were myelosuppression and radiation dermatitis. The median follow-up time was 32 months. For the whole group, the 3-year and 5-year overall survival (OS) rates and disease-free survival (DFS) were 71.1% and 63.6%, and 73.4% and 69.0%, respectively. Multivariate regression analysis showed that the T3-4 stage was an independent prognostic risk factor for OS, progression-free survival (PFS), and DFS. And M1 was an independent prognostic risk factor for PFS and DFS. Patients in stage M0 mainly treated with CRT had better local control than those mainly treated with surgery (p = 0.027). For M0 patients, induction chemotherapy combined with CRT tends to prolong OS compared with CRT alone (p = 0.26). The 3-year colostomy-free survival for the whole group was 81.1%., Conclusions: CRT is recommended as the first choice for the treatment of M0 stage ASCC. Induction chemotherapy may bring better survival benefits for some patients. Patients with ASCC in China seem to have a better local control rate, which suggested different treatment strategies may be needed in China., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: This study sought to develop and validate a lens opacities classification system based on ultrasound biomicroscopy (UBM) imaging to grade pediatric cataracts., Methods: The study was conducted at Guangzhou Children's Hospital, Guangzhou Women and Children's Medical Center. UBM images of patients at the hospital from September 2013 to November 2014 were used in this study. We summarized the characteristics of lenticular opacification in each of the following 4 zones: the anterior capsule (A); the cortex (C); the nucleus (N); and the posterior capsule (P). The UBM data and intraoperative videos were compared, and sensitivity, specificity, accuracy, and positive and negative predictive values were determined for our Lens Opacities Classification System based on UBM for Pediatric Cataracts (LOCS-UP) detection. Two physicians classified pediatric cataracts (anterior capsule, cortex, and posterior capsule) by extracting 146 images from the UBM database. Patients' data were recorded to calculate the kappa coefficients. The LOCS-UP was developed., Results: Under this standard, all types of pediatric cataracts can be classified and acquired a code by the LOCS-UP. The LOCS-UP had the highest sensitivity (100%) and specificity (98.96%) in naming the anterior capsule and the lowest sensitivity (50%) and specificity (89.59%) in naming the posterior capsule. Its consistency at naming the anterior capsule was satisfactory (Kappa coefficient: 0.70), and it was also able to name the nucleus, cortex, and posterior capsule (0.56, 0.58, and 0.48, respectively)., Conclusions: LOCS-UP could name pediatric cataracts by providing an unique digital encoding, which could reflect characteristics exactly for different local lens anomalies to all kinds of pediatric cataract patients. This method provides detailed and accurate information about Patients' lenses., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/qims-20-1028). The authors have no conflicts of interest to declare., (2021 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Cell state transitions control the functional behavior of cancer cells. Epithelial-to-mesenchymal transition (EMT) confers cancer stem cell-like properties, enhanced tumorigenicity and drug resistance to tumor cells, while mesenchymal-epithelial transition (MET) reverses these phenotypes. Using high-throughput chemical library screens, retinoids are found to be potent promoters of MET that inhibit tumorigenicity in basal-like breast cancer. Cell state transitions are defined by reprogramming of lipid metabolism. Retinoids bind cognate nuclear receptors, which target lipid metabolism genes, thereby redirecting fatty acids for β-oxidation in the mesenchymal cell state towards lipid storage in the epithelial cell state. Disruptions of key metabolic enzymes mediating this flux inhibit MET. Conversely, perturbations to fatty acid oxidation (FAO) rechannel fatty acid flux and promote a more epithelial cell phenotype, blocking EMT-driven breast cancer metastasis in animal models. FAO impinges on the epigenetic control of EMT through acetyl-CoA-dependent regulation of histone acetylation on EMT genes, thus determining cell states.

Purpose: We explored the feasibility and reproducibility of cardiac computed tomography (CCT)-derived left ventricular (LV) global strain in postoperative children
with congenital heart disease (CHD) and compared its correlation and agreement with transthoracic echocardiography (TTE)., Methods: Fifty-one patients (28 males, 23 females) were included who underwent clinically indicated retrospective electrocardiography-triggered CCT. and all patients underwent additional TTE on the same day. LV global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were measured. Correlations of global strains between CCT and TTE were assessed using Pearson's correlation coefficient. Intra-class correlation coefficients (ICC) were used to assess CCT intra-observer and inter-observer reproducibility., Results: GLS and GCS were not significantly different between CCT and TTE (GLS: -23.54 ± 3.24 vs. -23.85 ± 3.72, respectively, p = 0.415; GCS: -28.21 ± 3.55 vs. -28.79 ± 3.69, respectively, p = 0.155). GRS was significantly different between CCT and TTE (60.79 ± 15.11 vs. 41.73 ± 4.27, respectively, p < 0.001). There was good correlation between CCT- and TTE-derived GLS (r = 0.70, p < 0.001) and GCS (r = 0.68, p < 0.001), but GRS showed no correlation between CCT and TTE (r = 0.09, p = 0.54). CCT-derived global strain showed good intra- and inter-observer reproducibility (ICC = 0.86-0.92), except the inter-observer reproducibility for GRS (ICC = 0.77)., Conclusions: CCT was feasible for postoperative evaluation of LV global strain in pediatric patients with CHD with sufficient reproducibility. CCT-derived global strain can provide additional information in selected CHD patients with poor acoustic windows and who are intolerant to or have contraindications for cardiac magnetic resonance., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To explore the differences between hematological phenotypes of patients with different genotypes in gene mutations and deletion α- thalassemia., Methods: By screening the α- thalassemia gene test results in the First Affiliated Hospital, Sun Yat-Sen University from January 2015 to April 2020, the patients with mutation and deletion α- thalassemia were obtained, then the differences between hematological phenotypes of patients with different genotypes were analyzed., Results: There were 96 patients with mutation combined with deletion α- thalassemia from the results of 24 054 α- thalassemia patients screened out, including 79 patients with non-deletion Hb H disease (α T α/-- SEA ) and 17 patients with mild α- thalassemia (α T α/-α), the incidence was 0.42%. Except the number of red blood cells (RBC) and mean corpuscular volume (MCV), the hemoglobin (Hb) concentration, hematocrit (Ht), average red blood cell hemoglobin concentration (MCHC), average red blood cell hemoglobin amount (MCH), average red blood cell volume (MCV) of the patients with α T α/--SEA genotype were significantly lower than those with α T α/-α genotype. The Hb of the patients with α CS α/-- SEA and α QS α/-- SEA genotype was (86±20)g/L and (84±9)g/L, respectirely, which was significantly lower than (114±16) g/L of α WS α/-- SEA genotype (P<0.05); The MCHC of patients with α CS α/-- SEA and α QS α/-- SEA genotype was (278.8±8.5) g/L and (282.1±21.1)g/L, respectirely, which was also significantly lower than (315.4±19.5) g/L of α WS α/-- SEA genotype (P<0.05); There was no significant difference between the patients with α CS α/-- SEA and α QS α/-- SEA genotype in hematological phenotypes. Except MCH and MCV, there was no significant differences between the patients with α WS α/-- SEA and α T α/-α genotype in RBC, Hb, and Ht. The result of Hb A 2 was (2.3±0.9)% for only 27 patients who performed electrophoretic analysis. There was no significant difference between the patients with α T α/-- SEA and α T α/-α genotype in Hb A 2 , aslo among 3 types of the patients with α T α/-- SEA genotype., Conclusion: The hematological phenotype changes caused by α WS α/-- SEA genotype are similar to those of mild α- thalassemia, and both of them are significantly lighter than those patients with α CS α/-- SEA and α QS α/-- SEA genotype.

Objective: We explored the feasibility of cardiac computed tomography (CCT) to evaluate postoperative ventricular function in children with congenital heart disease (CHD) and evaluated the accuracy and reproducibility of CCT using cardiac magnetic resonance (CMR) as a reference., Methods: Thirty-two postoperative children with CHD (20 boys and 12 girls) who underwent CMR and CCT were enrolled. Left and right ventricular ejection fraction, end-diastolic volume, end-systolic volume, stroke volume, and cardiac index were measured using cardiac function analysis software. Cardiac function data were compared between CMR and CCT. The agreement between the 2 modalities was assessed using a Bland-Altman analysis. Intraclass correlation coefficients were used to assess intraobserver and interobserver reproducibility in CCT functional measurements., Results: All functional parameters showed no significant difference (P > 0.05) and were well-correlated (r > 0.5, P < 0.05) between CMR and CCT. The mean values of all ventricular function parameters in CCT were higher compared with CMR. As indicated by 95% limits of agreement, left ventricular function parameters showed a better level of agreement compared with right ventricular function parameters between the 2 modalities. Intraobserver and interobserver reproducibility were excellent in CCT measurements for all functional parameters (intraclass correlation coefficient > 0.9)., Conclusions: Compared with the criterion standard of CMR, CCT is feasible for assessing postoperative ventricular function with sufficient diagnostic accuracy and reproducibility in children with CHD. In addition to its important role regarding anatomical characterization, CCT is a suitable alternative and convenient follow-up tool that can be used to functional evaluation in children who are intolerant with CMR or have contraindications to CMR., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The aim of this study is to explore the feasibility of using a non-sedation protocol for the evaluation of neonatal congenital heart disease by using 16-cm wide-detector CT with a low radiation dose. Thirty-four neonates (group 1) were enrolled to undergo cardiac CT without sedation between August 2018 and March 2019. The control group (group 2) comprising 20 inpatient neonates was sedated. Cardiac CT was performed using 16-cm area detector 320-row CT with free breathing and prospective ECG-triggering scan mode. The examination completion time, radiation dose, and image quality were compared between the groups. The results of cardiac CT for patients in group 1 who underwent surgery were compared with surgical findings. Intergroup differences in body weight, age, examination completion time, radiation dose, and image quality evaluation were not significant. There was no significant difference in oxygen saturation before and after the examination in group 1. In all, 98 separate cardiovascular abnormalities in 27 group 1 patients were confirmed using surgical reports. The overall sensitivity, specificity, positive predictive value, and negative predictive value of cardiac CT were 94.90%, 100.0%, 100.0%, and 98.53%. The non-sedation protocol can be applied in neonates with congenital heart disease by using 16-cm wide-detector CT with a low radiation dose. Based on the image quality obtained, non-sedative examination did not extend the examination completion time and helped avoid the possible side effects of sedative drugs., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature.)

Adipogenesis of bone marrow mesenchymal stem cells (MSCs) promotes chemoresistance of acute myeloid leukaemia (AML) cells. MSCs from AML patients (AML-MSCs) display enhanced adipogenesis compared with bone marrow MSCs from healthy donors. However, the precise molecular mechanism by which adipogenesis of MSCs from AML marrow differs from normal counterparts remains obscure. We found that METTL3 significantly inhibits MSC adipogenesis. Here, we aimed to identify the molecular mechanism linking METTL3 and MSC adipogenesis. Analysis of m 6 A epigenetic changes in MSCs determined via RIP-qPCR and MeRIP-qPCR indicated that METTL3 affects AKT protein expression in MSCs by mediating m 6 A modification of AKT1-mRNA. Downregulated METTL3 expression in AML-MSCs induced an increase in AKT protein, resulting in enhanced MSC adipogenesis, thereby contributing to chemoresistance in AML cells. Therefore, targeting AKT regulation by mRNA modification in MSC adipogenesis might provide a novel therapeutic strategy to overcome AML chemoresistance., (© 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Background: Patients with locally advanced sigmoid colon cancer (LASCC) have limited treatment options and a dismal prognosis with poor quality of life. This retrospective study aimed to further evaluate the feasibility and efficacy of neoadjuvant chemoradiotherapy (NACRT) followed by surgery as treatment for select patients with unresectable LASCC., Methods: We studied patients with unresectable LASCC who received NACRT between November 2010 and April 2019. The NACRT regimen consisted of intensity modulated radiotherapy (IMRT) of 50 Gy to the gross tumor and positive lymphoma node and 45 Gy to the clinical target volume. Capecitabine‑based chemotherapy was administered every 2 (mFOLFOX6) or 3 weeks (CAPEOX). Surgery was scheduled 6-8 weeks after radiotherapy., Results: Seventy‑two patients were enrolled in this study. Patients had a regular follow-up (median, 41.1 months; range, 8.3-116.5 months). Seventy‑one patients completed NACRT, and sixty-five completed surgery. Resection with microscopically negative margins (R0 resection) was achieved in 64 patients (88.9%). Pathologic complete response was observed in 15 patients (23.1%), and multivisceral resection was necessary in 38 patients (58.3%). The cumulative probability of 3-year overall survival (OS) and progression-free survival (PFS) were 75.8 and 70.7%, respectively., Conclusions: For patients with unresectable LASCC, neoadjuvant chemoradiotherapy is feasible, surgery can be performed safely and may result in increased survival and organ preservation rates.

Background: Ubiquitin-conjugating enzyme E2W (UBE2W) is a protein-coding gene that has an important role in ubiquitination and may be vital in the repair of DNA damage. However, studies on the prognostic value of UBE2W and its correlation with tumor-infiltrating immune cells in multiple cancers have not been addressed., Methods: We investigated UBE2W expression in the Oncomine database, the Tumor Immune Estimation Resource (TIMER), TNMplot database. Then, the clinical prognostic value of UBE2W was analyzed via online public databases. Meanwhile, we explored the correlation between UBE2W and DNA repair associate genes expression and DNA methyltransferase expression by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA). By using the same method, the correlation between UBE2W and tumor-infiltrating immune cells was explored. Genomic Profiles of UBE2W in breast cancer (BRCA) were accessed in cBioPortal (v3.5.0). Functional proteins associated network was analyzed by STRING database (v11.0)., Results: UBE2W was abnormally expressed and significantly correlated with mismatch repair (MMR) gene mutation levels, DNA methyltransferase, and BRCA1/2 expression in breast cancer. High expression of UBE2W may promote the tumor immunosuppression and metastasis, induce endocrine therapy resistance and deteriorate outcomes of patients with breast cancer. These findings suggest that UBE2W could be a potential biomarker of prognosis and tumor-infiltrating immune cells. Besides, RBX1 may be a new E3 that was regulated by UBE2W., Conclusions: Ubiquitin E2 UBE2W is a potential prognostic biomarker and is correlated with immune infiltration in BRCA.

In the last few decades, the incidences of obesity and related metabolic disorders worldwide have increased dramatically. Major pathophysiology of obesity is termed "lipotoxicity" in modern western medicine (MWM) or "dampness-heat" in traditional Chinese medicine (TCM). "Dampness-heat" is a very common and critically important syndrome to guild clinical treatment in TCM. However, the pathogenesis of obesity in TCM is not fully clarified, especially by MWM theories compared to TCM. In this review, the mechanism underlying the action of TCM in the treatment of obesity and related metabolic disorders was thoroughly discussed, and prevention and treatment strategies were proposed accordingly. Hypoxia and inflammation caused by lipotoxicity exist in obesity and are key pathophysiological characteristics of "dampness-heat" syndrome in TCM. "Dampness-heat" is prevalent in chronic low-grade systemic inflammation, prone to insulin resistance (IR), and causes variant metabolic disorders. In particular, the MWM theories of hypoxia and inflammation were applied to explain the "dampness-heat" syndrome of TCM, and we summarized and proposed the pathological path of obesity: lipotoxicity, hypoxia or chronic low-grade inflammation, IR, and metabolic disorders. This provides significant enrichment to the scientific connotation of TCM theories and promotes the modernization of TCM., 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 Zhang, Sheng, Xie, Luo, Xue, Xu and Chen.)

Background: The management of unresectable locally advanced colon cancer (LACC) remains controversial, as resection is not feasible. The goal of this study was to evaluate the treatment outcomes and toxicity of neoadjuvant chemoradiotherapy (NACRT) followed with surgery and adjuvant chemotherapy in patients with unresectable radically LACC., Methods: We included patients who were diagnosed at our institution, 2010-2018. The neoadjuvant regimen consisted of radiotherapy and capecitabine/ 5-fluorouracil-based chemotherapy., Results: One hundred patients were identified. The median follow-up time was 32 months. The R0 resection rate, adjusted nonmultivisceral resection rate and bladder preservation rate were 83.0, 43.0 and 83.3%, respectively. The pCR and clinical-downstaging rates were 18, and 81.0%%, respectively. The 3-year PFS and OS rates for all patients were 68.6 and 82.1%, respectively. Seventeen patients developed grade 3-4 myelosuppression, which was the most common adverse event observed after NACRT. Tumor perforation occurred in 3 patients during NACRT. The incidence of grade 3-4 surgery-related complications was 7.0%. Postoperative anastomotic leakage was observed in 3 patients., Conclusions: NACRT followed by surgery was feasible and safe for selected patients with LACC, and can be used as a conversion treatment to achieve satisfactory downstaging, long-term survival and quality of life, with acceptable toxicities.

Background: The watch-and-wait strategy offers a non-invasive therapeutic alternative for rectal cancer patients who have achieved a clinical complete response (cCR) after chemoradiotherapy. This study aimed to investigate the long-term clinical outcomes of this strategy in comparation to surgical resection., Methods: Stage II/III rectal adenocarcinoma patients who received neoadjuvant chemoradiotherapy and achieved a cCR were selected from the databases of three centers. cCR was evaluated by findings from digital rectal examination, colonoscopy, and radiographic images. Patients in whom the watch-and-wait strategy was adopted were matched with patients who underwent radical resection through 1:1 propensity score matching analyses. Survival was calculated and compared in the two groups using the Kaplan-Meier method with the log rank test., Results: A total of 117 patients in whom the watch-and-wait strategy was adopted were matched with 354 patients who underwent radical resection. After matching, there were 94 patients in each group, and no significant differences in term of age, sex, T stage, N stage or tumor location were observed between the two groups. The median follow-up time was 38.2 months. Patients in whom the watch-and-wait strategy was adopted exhibited a higher rate of local recurrences (14.9% vs. 1.1%), but most (85.7%) were salvageable. Three-year non-regrowth local recurrence-free survival was comparable between the two groups (98% vs. 98%, P = 0.506), but the watch-and-wait group presented an obvious advantage in terms of sphincter preservation, especially in patients with a tumor located within 3 cm of the anal verge (89.7% vs. 41.2%, P < 0.001). Three-year distant metastasis-free survival (88% in the watch-and-wait group vs. 89% in the surgical group, P = 0.874), 3-year disease-specific survival (99% vs. 96%, P = 0.643) and overall survival (99% vs. 96%, P = 0.905) were also comparable between the two groups, although a higher rate (35.7%) of distant metastases was observed in patients who exhibited local regrowth in the watch-and-wait group., Conclusion: The watch-and-wait strategy was safe, with similar survival outcomes but a superior sphincter preservation rate as compared to surgery in rectal cancer patients achieving a cCR after neoadjuvant chemoradiotherapy, and could be offered as a promising conservative alternative to invasive radical surgery.

Objectives: The relationship between the 18 FDG PET-CT maximum standard uptake value (SUVmax) and the type of lung adenocarcinoma is still not established. The aim of this study was to investigate the relationship between SUVmax value and histological grade and pathological subtype of lung adenocarcinoma, and to determine the optimum SUVmax cutoffs for distinguishing different histological grades., Materials and Methods: The data of 618 lung adenocarcinoma patients were retrospectively analyzed. The relationship between SUVmax measured on preoperative 18 FDG-PET-CT and the histological grade and pathological subtype was examined. The Kruskal-Wallis test was used to compare differences among groups, and the Bonferroni-Dunn test for pairwise comparison among groups. ROC analysis was applied to determine the optimal cut-off values for distinguishing different groups. In addition, the cut-off value was verified in an independent cohort of 85 consecutive lung adenocarcinoma cases., Results: The SUVmax was significantly different between the low, intermediate, and high-grade groups(p < .001). SUVmax value increased with increase in the degree of malignancy. The optimal cut-off value for identifying low-grade tumors was 2.01 (sensitivity 90.4%, specificity 86.9%, area under the curve [AUC] = 0.928, 95% confidence interval: 0.91-0.95; p < .001). The optimal cutoff SUVmax value for identifying high-grade tumors was 7.41 (sensitivity 79.8%, specificity 73.5%, AUC = 0.830, 95% confidence interval: 0.79-0.87; p < .001). The validation experiment showed that the coincidence rate was 88.89% in the low-level group, 64.15% in the middle-level group, and 78.57% in the high-level group., Conclusion: SUVmax can be used to predict pathological subtype and histological grade of lung adenocarcinoma. Thus, 18 FDG PET-CT can serve as a noninvasive tool for precise diagnosis and help in the preoperative formulation of patient-specific treatment strategies., (Copyright © 2020 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Small regulatory RNAs (sRNAs) finely control gene expression in prokaryotes and synthetic sRNA has become a useful high-throughput approach to tackle current challenges in metabolic engineering because of its many advantages compared to conventional gene knockouts. In this review, we first focus on the modular structures of sRNAs and rational design strategies of synthetic sRNAs on the basis of their modular structures. The wide applications of synthetic sRNAs in bacterial metabolic engineering, with or without the aid of heterogeneously expressed Hfq protein, were also covered. In addition, we give attention to the improvements in implementing synthetic sRNAs, which make the synthetic sRNA strategy universally applicable in metabolic engineering and synthetic biology. KEY POINTS: • Synthetic sRNAs can be rationally designed based on modular structures of natural sRNAs. • Synthetic sRNAs were widely used for metabolic engineering in various microorganisms. • Several technological improvements made the synthetic sRNA strategy more applicable.

In vivo cell fate reprogramming has emerged as a new method for understanding cell plasticity and as potential treatment for tissue regeneration. Highly efficient and precise reprogramming requires fully understanding of the transcriptomes which function within different cell types. Here, we adopt weighted gene co-expression network analysis (WGCNA) to explore the molecular mechanisms of self-renewal in several well-known stem cell types, including embryonic stem cells (ESC), primordial germ cells (PGC), spermatogonia stem cells (SSC), neural stem cells (NSC), mesenchymal stem cells (MSC), and hematopoietic stem cells (HSC). We identified 37 core genes that were up-regulated in all of the stem cell types examined, as well as stem cell correlated gene co-expression networks. The validation of the co-expression genes revealed a continued protein-protein interaction network that included 823 nodes and 3113 edges. Based on the topology, we identified six densely connected regions within the continued protein-protein interaction network. The SSC specific genes Itgam , Cxcr6 , and Agtr2 bridged four densely connected regions that consisted primarily of HSC-, NSC-, and MSC-correlated genes. The expression levels of identified stem cell related transcription factors were confirmed consistent with bioinformatics prediction in ESCs and NSCs by qPCR. Exploring the mechanisms underlying adult stem cell self-renewal will aid in the understanding of stem cell pool maintenance and will promote more accurate and efficient strategies for tissue regeneration and repair., (Copyright © 2020 Wang, Li, Hou, Song, Xie and Shen.)

Obesity-induced inflammation, characterized by augmented infiltration and altered balance of macrophages, is a critical component of systemic insulin resistance. Chemokine-chemokine receptor system plays a vital role in the macrophages accumulation. CC-Chemokine Receptor-like 2 (Ccrl2) is one of the receptors of Chemerin, which is a member of atypical chemokine receptors (ACKR) family, reported taking part in host immune responses and inflammation-related conditions. In our study, we found ccrl2 expression significantly elevated in visceral adipose tissue (VAT) of high fat diet (HFD) induced obese mice and ob/ob mice. Systemic deletion of Ccrl2 gene aggravated HFD induced obesity and insulin resistance and ccrl2 -/- mice showed aggravated VAT inflammation and increased M1/M2 macrophages ratio, which is due to the increase of macrophages chemotaxis in Ccrl2 deficiency mice. Cumulatively, these results indicate that Ccrl2 has a critical function in obesity and obesity-induced insulin resistance via mediating macrophages chemotaxis., (© 2020 Chongqing Medical University. Production and hosting by Elsevier B.V.)

Background: Right ventricular dilation and dysfunction is a common long-term complication in patients with repaired pulmonary stenosis (rPS). Additionally, abnormal right and left ventricular interactions have been reported in right-sided heart defect after intervention, including in pulmonary stenosis., Purpose: To analyze ventricular strain, remodeling, and left and right ventricular interactions in rPS patients with preserved right ventricular ejection fraction (RVEF) compared with healthy children using cardiac magnetic resonance., Study Type: A cross-sectional study., Population: In all, 34 rPS patients and 10 healthy children volunteers (controls)., Field Strength/sequence: 3.0T/2D balanced steady-state free precession (2D b-SSFP) cine, late gadolinium enhancement (LGE), and 2D phase contrast (2D-PC)., Assessment: Pulmonary regurgitation (PR) fractions of the main pulmonary artery, biventricular volumes, masses, function, and cardiac strain., Statistical Tests: Mann-Whitney U-test, t-test, Pearson correlation coefficients, Spearman's correlation coefficients, and intraclass correlation coefficients analysis were performed., Results: For group analysis, the right ventricular (RV) global circumferential strain and radial strain were significantly increased in patients when compared with controls (-13.57 ± 2.69 vs. -5.91 ± 3.16, P < 0.001; 25.31 ± 8.12 vs. 9.87 ± 5.32, P < 0.001, respectively). The fraction of PR displayed moderate correlation with right ventricular end-diastolic volume index (RVEDVi) (r = 0.452, P = 0.022). RVEDVi and mass index were larger in patients vs. control (104.92 ± 27.46 vs. 85.15 ± 11.98, P = 0.016; 18.28 ± 4.95g/m 2 vs. 11.67 ± 2.14 g/m 2 , P < 0.001, respectively). Patients presented with preserved left ventricular ejection function, but was lower than healthy controls (60.89% ± 4.89% vs. 65.95% ± 4.56%, P = 0.006). Regional circumferential strain of segment 3 of left ventricle (LV) were significantly decreased in patients (-7.79 ± 6.52 vs. -13.56 ± 3.22, P = 0.003)., Data Conclusion: Compensated increased RV strain, myocardial remodeling of RV, and adverse right and left ventricular interactions occur in rPS patients with preserved RVEF. The decreased interventricular septum strain may lead to impaired LV function due to RV dilation as a result of PR., Level of Evidence: 3 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;52:129-138., (© 2020 International Society for Magnetic Resonance in Medicine.)

Objective: Hepatitis B virus X protein (HBx) is a pivotal factor for HBV-induced hepatitis. Herein, we sought to investigate HBx-mediated NLR pyrin domain containing 3 (NLRP3) inflammasome activation and pyroptosis under oxidative stress., Methods: The effect of HBx on the NLRP3 inflammasome was analyzed by enzyme-linked immunosorbent assays, quantitative reverse transcription-polymerase chain reaction, western blotting, and immunofluorescence in hepatic HL7702 cells. Pyroptosis was evaluated by western blotting, lactate dehydrogenase release, propidium iodide staining, and transmission electron microscopy. NLRP3 expression in the inflammasome from liver tissues was assessed by immunohistochemistry., Results: In hydrogen peroxide (H 2 O 2 )-stimulated HL7702 cells, HBx triggered the release of pro-inflammatory mediators apoptosis-associated speck-like protein containing a CARD (ASC), interleukin (IL)-1β, IL-18, and high-mobility group box 1 (HMGB1); activated NLRP3; and initiated pro-inflammatory cell death (pyroptosis). HBx localized to the mitochondria, where it induced mitochondrial damage and production of mitochondrial reactive oxygen species (mitoROS). Treatment of HL7702 cells with a mitoROS scavenger attenuated HBx-induced NLRP3 activation and pyroptosis. Expression levels of NLRP3, ASC, and IL-1β in liver tissues from patients were positively correlated with HBV DNA concentration., Conclusions: The NLRP3 inflammasome was activated by elevated mitoROS levels and mediated HBx-induced liver inflammation and hepatocellular pyroptosis under H 2 O 2 -stress conditions.

A poly(St-co-EGDMA)@poly(4-vinylpyridine-co-EGDMA) composite polymer was synthesised by precipitation reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymer was investigated as a sorbent for extraction of synthetic food dyes: ponceau 4R, tartrazine, sunset yellow, brilliant blue and erythrosine from soft drinks. The morphology and composition of the polymer were characterized and confirmed respectively by scanning electron microscopy and Fourier-transform infrared spectroscopy. The pH dependence experiment revealed that the adsorption of food dyes by the polymer was pH dependent and the maximum adsorption was achieved at pH 3. Adsorption between the polymer and the dyes was mainly due to electrostatic interaction. Under the optimized pH conditions, the polymer was saturated with the dye solutions at a concentration of about 200 μg mL-1 and exhibited a maximum adsorption capacity of 9 μg mg-1. The values were higher than those for polyamide, a sorbent used in the standard method. The recovery from the real samples of the three spiked concentrations 10, 50 and 100 μg mL-1 was respectively within the ranges of 83.2-107.2%, 94.5-110.7% and 79.2-111.5%, with a SD within ±4%. The sorbent could be reused more than 10 times with a recovery higher than 80%. The small volume requirement of the sample and sorbent during the sample pre-treatment, indicated that poly(St-co-EGDMA)@poly(4-vinylpyridine-co-EGDMA) was a potential material for food dye extraction in an environment-friendly and economical manner.

Hepatitis B virus × protein (HBx) serves an important role in the pathogenesis of the hepatitis B virus infection. Previous studies have reported that the interaction between HBx and hepatocyte mitochondria is an important factor leading to liver cell injury and apoptosis, ultimately inducing the formation of liver cancer. In the present study, a mouse model expressing HBx was constructed using hydrodynamic in vivo transfection based on the interaction between HBx and cytochrome c oxidase (COX) subunit III. The specific mechanism of HBx-induced oxidative stress in mouse hepatocytes and the subsequent effect on mitochondrial function and inflammatory injury was assessed. The results demonstrated that HBx reduced the activity of COX and the expression of superoxide dismutase and upregulated the expression of malondialdehyde, NF-κB and phospho-AKT, thus increasing oxidative stress. In addition, HBx induced an increase in interleukin (IL)-6, IL-1β and IL-18 expression levels, which created an inflammatory microenvironment in the liver, further promoting hepatocyte inflammatory injury. Therefore, it was proposed that HBx may affect hepatocyte mitochondrial respiration by reducing the activity of cytochrome c oxidase, leading to mitochondrial dysfunction and inducing hepatocyte inflammation and injury., (Copyright: © Ling et al.)

Breast cancer is the most common cancer observed in adult females, worldwide. Due to the heterogeneity and varied molecular subtypes of breast cancer, the molecular mechanisms underlying carcinogenesis in different subtypes of breast cancer are distinct. Recently, long noncoding RNAs (lncRNAs) have been shown to be oncogenic or play important roles in cancer suppression and are used as biomarkers for diagnosis and therapy. In this study, we identified 134 lncRNAs and 6,414 coding genes were differentially expressed in triple-negative (TN), human epidermal growth factor receptor 2- (HER2-) positive, luminal A-positive, and luminal B-positive breast cancer. Of these, 37 lncRNAs were found to be dysregulated in all four subtypes of breast cancers. Subtypes of breast cancer special modules and lncRNA-mRNA interaction networks were constructed through weighted gene coexpression network analysis (WGCNA). Survival analysis of another public datasets was used to verify the identified lncRNAs exhibiting potential indicative roles in TN prognosis. Results from heat map analysis of the identified lncRNAs revealed that five blocks were significantly displayed. High expressions of lncRNAs, including LINC00911, CSMD2-AS1, LINC01192, SNHG19, DSCAM-AS1, PCAT4, ACVR28-AS1, and CNTFR-AS1, and low expressions of THAP9-AS1, MALAT1, TUG1, CAHM, FAM2011, NNT-AS1, COX10-AS1, and RPARP-AS1 were associated with low survival possibility in TN breast cancers. This study provides novel lncRNAs as potential biomarkers for the therapeutic and prognostic classification of different breast cancer subtypes., 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 © 2020 Xiao-Xiao Li et al.)

Purpose: Radiotherapy is an effective treatment for many types of cancer in clinical settings. Gel dosimetry has the potential to record three-dimensional (3D) dose distribution compared to a conventional ion chamber. As the elasticity of the gel is altered after irradiation due to gel polymerization, we aim to measure the dose recorded in gel dosimetry with ultrasonic shear wave elasticity imaging (SWEI), a nondestructive and quantitative elasticity imaging tool., Methods: In this study, a cylindrical N-isopropylacrylamide (NIPAM) polymer gel with a diameter of 10 cm and a height of 10 cm and with cellulose as an ultrasonic scatterer was irradiated by a linear accelerator with the irradiation parameters of 6 MV x-ray, dose rate of 100 cGy/min and field size of 10  ×  20 mm 2 . The six gel phantoms were irradiated with the dose of 0, 1, 3, 5, 8, or 10 Gy. The gel phantoms were measured with SWEI at 24, 36, and 48 h after x-ray irradiation. The two-dimensional (2D) shear wave velocity and Young's modulus maps corresponding to x-ray dose distribution were reconstructed following a time-of-flight reconstruction from a set of time-series displacement maps. The spatial resolution of the reconstructed SWEI image is ~1 mm., Results: Our results show that the elastic modulus increases linearly as irradiation dose increases (R 2  = 0.94 at 24 h, R 2  = 0.98 at 36 h, R 2  = 0.98 at 48 h), suggesting that the gel elasticity is highly associated with x-ray irradiation dose at 36 h post irradiation, and the dose resolution was 0.66 kPa/Gy. From the 3D elastic modulus maps, the dose distribution along the depth and lateral direction can be reflected in the NIPAM gel dosimetry using SWEI as well., Conclusions: In this study, the irradiated NIPAM gel phantom was quantitatively measured with SWEI for the first time to read the dose distribution recorded in the gel dosimetry. The results suggest that the gel elasticity is highly associated with x-ray irradiation dose. In the future, 2D/or 3D dose distribution from intensity modulated radiotherapy (IMRT) or other potential particle radiotherapy will be measured and reconstructed with SWEI and compared with the dose map from a treatment planning system (TPS) in the clinic., (© 2020 American Association of Physicists in Medicine.)

Objective: To investigate the effect of the long chain non-coding RNA H19 (lncRNA H19) on the invasion and migration of oral cancer cells and its related molecular mechanism., Methods: The expression levels of lncRNA H19, miR-107, and cyclin-dependent kinase 6 (CDK6) in the immortalized oral epithelial cell line HIOEC and the oral cancer cell line CAL27 were detected by real-time quantitative polymerase chain reaction. CAL27 cells were transfected with siRNA H19, miR-107 mimics, pcDNA H19, or anti-miR-107, and the effects of H19 and miR-107 on the invasion and migration of cells were examined via Transwell assay. The TargetScan database predicted the targeting of H19, miR-107, and CDK6. Double luciferase reporter gene assay was performed to detect interactions among H19, miR-107, and CDK6. Western blot analysis was conducted to examine the effects of H19 and miR-107 on the protein level of the target gene CDK6., Results: Compared with that in HIOEC cells, the expression of H19 was significantly increased in CAL27 cells (P<0.05). After transfection with siRNA H19, the expression of H19 decreased, and the invasion and migration ability of CAL27 cells were inhibited (P<0.05). H19 could bind specifically to the 3'-UTR of miR-107 to modulate the expression of miR-107. Compared with that in HIOEC cells, the expression of miR-107 significantly decreased in CAL27 cells (P<0.05). The expression of miR-107 increased after transfection with siRNA H19, and anti-mir-107 co-transfection could promote the invasion and migration ability of siRNA H19 in CAL27 cells (P<0.05). Compared with that in HIOEC cells, CDK6 expression significantly increased in CAL27 cells (P<0.05), and the expression level of the gene was coregulated by H19 and miR-107 (P<0.05)., Conclusions: lncRNA H19 plays an important role in the development of oral cancer. It can regulate the invasion and migration of oral cancer cells by targeting the miR-107/CDK6 signaling axis.

Purpose: To evaluate the outcomes of 45 Gy/15 fractions/once-daily and 45 Gy/30 fractions/twice-daily radiation schemes utilizing intensity-modulated radiation therapy (IMRT) in extensive stage small cell lung cancer (SCLC), and to build up a new radiobiological model for tumor control probability (TCP) considering multiple biological effects., Methods: Fifty-eight consecutive patients diagnosed with extensive stage SCLC, treated with chemotherapy and chest irradiation, were retrospectively reviewed. Thirty-seven received hyperfractionated IMRT (Hyper-IMRT, 45 Gy/30 fractions/twice-daily) and 21 received hypofractionated IMRT (Hypo-IMRT, 45 Gy/15 fractions/once-daily). Local progression-free survival (LPFS) and overall survival (OS) were calculated and compared. An extended linear-quadratic (LQ) model, LQRG, incorporating cell repair, redistribution, reoxygenation, regrowth and Gompertzian tumor growth was created based on the clinical data. The TCP model was reformulated to predict LPFS. The classical LQ and TCP models were compared with the new models. Akaike information criterion (AIC) was used to assess the quality of the models., Results: The 2-year LPFS (34.1% vs 27.9%, p = 0.44) and OS (76.9% vs 76.9%, p = 0.26) were similar between Hyper- and Hypo-IMRT patients. According to the LQRG model, the α/β calculated was 9.2 (95% confidence interval: 8.7-9.9) Gy after optimization. The average absolute and relative fitting errors for LPFS were 9.1% and 18.7% for Hyper-IMRT, and 8.8% and 16.2% for Hypo-IMRT of the new TCP model, compared with 29.1% and 62.3% for Hyper-IMRT, and 30.7% and 65.3% for Hypo-IMRT of the classical model., Conclusions: Hypo- and Hyper-IMRT resulted in comparable local control in the chest irradiation of extensive stage SCLC. The LQRG model has better performance in predicting the TCP (or LPFS) of the two schemes., (Copyright © 2019. Published by Elsevier B.V.)

A four-step route for the synthesis of 2-methoxyestradiol (5) starting from 17β-estradiol (1) has been achieved with a 51% overall yield. The key step was the ruthenium-catalyzed ortho-C(sp 2 )-H bond hydroxylation of aryl carbamates. Using dimethyl carbamate as the directing group, [RuCl 2 (p-cymene)] 2 as the catalyst, PhI(OAc) 2 as the oxidant and trifluoroacetate/trifluoroacetic anhydride (1:1) as the co-solvent, the hydroxyl group could be singly installed at the 2-position of 3-dimethylcarbamoyloxyestradiol (2) with 65% yield. Subsequent methylation of hydroxy and removal of dimethyl carbamate afforded 2-methoxyestradiol (5)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A high-content GABA was found in Sojae Semen Praeparatum(SSP), which is a famous traditional Chinese medicine and officially listed in Chinese Pharmacopoeia. To screen out and identify GABA-producing microbes from samples at different time points during the fermenting process of SSP, traditional microbiological methods combined with molecular biological methods were used to study the predominant GABA-producing microorganisms existing in the fermenting process of SSP. This study would lay a foundation for further studying the processing mechanism of SSP. The fermenting process of SSP was based on Chinese Pharmacopoeia(2010 edition), and samples were taken at different time points during the fermenting process of SSP. The bacteria and fungi from samples at different time points in the fermenting process of SSP were cultured, isolated and purified by selective medium, and dominant strains were selected. The dominant bacteria were cultured in the designated liquid medium to prepare the fermentation broths, and GABA in the fermentation broth was qualitatively screened out by thin-layer chromatography. The microbial fermentation broth with GABA spots in the primary screening was quantitatively detected by online pre-column derivatization and high performance liquid chromatography established in our laboratory. GABA-producing microorganisms were screened out from predominant strains, and their GABA contents in fermentation broth were determined. The DNA sequences of GABA-producing bacteria and fungi were amplified using 16S rDNA and 18S rDNA sequences by PCR respectively. The amplified products were sequenced, and the sequencing results were identified through NCBI homology comparison. Molecular biological identification was made by phylogenetic tree constructed by MEGA 7.0 software. Through the homology comparison of NCBI and the construction of phylogenetic tree by MEGA 7.0 software, nine GABA-producing microorganisms were screened out and identified in this study. They were Bacillus subtilis, Enterococcus faecium, E. avium, Aspergillus tamarii, A. flavus, A. niger, Cladosporium tenuissimum, Penicillium citrinum and Phanerochaete sordida respectively. For the first time, nine GABA-producing microorganisms were screened out and identified in the samples at different time points during the fermenting process of SSP in this study. The results indicated that multiple predominant GABA-producing microorganisms exist in the fermenting process of SSP and may play an important role in the formation of GABA.

Schizophrenia is a complex psychiatric disorder with high genetic heterogeneity, however, the contribution of rare mutations to the disease etiology remains to be further elucidated. We herein performed exome sequencing in a Han Chinese schizophrenia family and identified a missense mutation (c.6724C>T, p.R2242C) in the teneurin transmembrane protein 4 ( TENM4 ) gene in the SCZD2 locus, a region previously linked to schizophrenia at 11q14-21. The mutation was confirmed to co-segregate with the schizophrenia phenotype in the family. Subsequent investigation of TENM4 exons 31, 32, and 33 adjacent to the p.R2242C mutation revealed two additional missense mutations in 120 sporadic schizophrenic patients. Residues mutated in these mutations, which are predicted to be deleterious to protein function, were highly conserved among vertebrates. These rare mutations were not detected in 1000 Genomes, NHLBI Exome Sequencing Project databases, or our in-house 1136 non-schizophrenic control exomes. Analysis of RNA-Seq data showed that TENM4 is expressed in the brain with high abundance and specificity. In line with the important role of TENM4 in central nervous system development, our findings suggested that increased rare variants in TENM4 could be associated with schizophrenia, and thus TENM4 could be a novel candidate gene for schizophrenia in the SCZD2 locus.

The inflammasome is a critical molecular complex that activates interleukin-1 driven inflammation in response to pathogen- and danger-associated signals. Germline mutations in the inflammasome sensor NLRP1 cause Mendelian systemic autoimmunity and skin cancer susceptibility, but its endogenous regulation remains less understood. Here we use a proteomics screen to uncover dipeptidyl dipeptidase DPP9 as a novel interacting partner with human NLRP1 and a related inflammasome regulator, CARD8. DPP9 functions as an endogenous inhibitor of NLRP1 inflammasome in diverse primary cell types from human and mice. DPP8/9 inhibition via small molecule drugs and CRISPR/Cas9-mediated genetic deletion specifically activate the human NLRP1 inflammasome, leading to ASC speck formation, pyroptotic cell death, and secretion of cleaved interleukin-1β. Mechanistically, DPP9 interacts with a unique autoproteolytic domain (Function to Find Domain (FIIND)) found in NLRP1 and CARD8. This scaffolding function of DPP9 and its catalytic activity act synergistically to maintain NLRP1 in its inactive state and repress downstream inflammasome activation. We further identified a single patient-derived germline missense mutation in the NLRP1 FIIND domain that abrogates DPP9 binding, leading to inflammasome hyperactivation seen in the Mendelian autoinflammatory disease Autoinflammation with Arthritis and Dyskeratosis. These results unite recent findings on the regulation of murine Nlrp1b by Dpp8/9 and uncover a new regulatory mechanism for the NLRP1 inflammasome in primary human cells. Our results further suggest that DPP9 could be a multifunctional inflammasome regulator involved in human autoinflammatory diseases., (© 2018 Zhong et al.)

Photosynthetic microalgae are of burgeoning interest in the generation of commercial bioproducts. Microalgae accumulate high lipid content under adverse conditions, which in turn compromise their growth and hinder their commercial potential. Hence, it is necessary to engineer microalgae to mitigate elevated lipid accumulation and biomass. In this study, we identified acetyl-CoA carboxylase (ACCase) in oleaginous microalga Phaeodactylum tricornutum (PtACC2) and expressed constitutively in the chloroplast to demonstrate the potential of chloroplast engineering. Molecular characterization of transplastomic microalgae revealed that PtACC2 was integrated, transcribed and expressed successfully, and localized in the chloroplast. Enzymatic activity of ACCase was elevated by 3.3-fold, and the relative neutral lipid content increased substantially by 1.77-fold, and lipid content reached up to 40.8% of dry weight. Accordingly, the number and size of oil bodies markedly increased. Fatty acid profiling showed that the content of monounsaturated fatty acids increased, while polyunsaturated fatty acids decreased. This method provides a valuable genetic engineering toolbox for microalgal bioreactors with industrial significance.

Calcium/calmodulin-dependent protein kinase II (CAMK2) plays fundamental roles in synaptic plasticity that underlies learning and memory. Here, we describe a new recessive neurodevelopmental syndrome with global developmental delay, seizures and intellectual disability. Using linkage analysis and exome sequencing, we found that this disease maps to chromosome 5q31.1-q34 and is caused by a biallelic germline mutation in CAMK2A . The missense mutation, p.His477Tyr is located in the CAMK2A association domain that is critical for its function and localization. Biochemically, the p.His477Tyr mutant is defective in self-oligomerization and unable to assemble into the multimeric holoenzyme. In vivo , CAMK2A H477Y failed to rescue neuronal defects in C. elegans lacking unc-43 , the ortholog of human CAMK2A. In vitro , neurons derived from patient iPSCs displayed profound synaptic defects. Together, our data demonstrate that a recessive germline mutation in CAMK2A leads to neurodevelopmental defects in humans and suggest that dysfunctional CAMK2 paralogs may contribute to other neurological disorders., Competing Interests: PC, FZ, SN, CB, KU, RZ, HL, AE, SN, WX, SA, ME, MS, MP, MA, BR No competing interests declared, (© 2018, Chia et al.)

Administration of exosomes derived from mesenchymal stromal cells (MSCs) could improve some neurologic conditions by transferring functional biomolecules to recipient cells. Furthermore, exosomes from hypoxic progenitor cells exerted better therapeutic effects in organ injury through specific cargoes. However, there are no related reports about whether exosomes derived from MSCs or hypoxia-preconditioned MSCs (PC-MSCs) could prevent memory deficits in Alzheimer disease (AD). In this study, the exosomes derived from MSCs or PC-MSCs were systemically administered to transgenic APP/PS1 mice. The expression of miR-21 in MSCs was significantly increased after hypoxic treatment. Injection of exosomes from normoxic MSCs could rescue cognition and memory impairment according to results of the Morris water maze test, reduced plaque deposition, and Aβ levels in the brain; could decrease the activation of astrocytes and microglia; could down-regulate proinflammatory cytokines (TNF-α and IL-1β); and could up-regulate anti-inflammatory cytokines (IL-4 and -10) in AD mice, as well as reduce the activation of signal transducer and activator of transcription 3 (STAT3) and NF-κB. Compared to the group administered exosomes from normoxic MSCs, in the group administered exosomes from PC-MSCs, learning and memory capabilities were significantly improved; the plaque deposition and Aβ levels were lower, and expression of growth-associated protein 43, synapsin 1, and IL-10 was increased; and the levels of glial fibrillary acidic protein, ionized calcium-binding adaptor molecule 1, TNF-α, IL-1β, and activation of STAT3 and NF-κB were sharply decreased. More importantly, exosomes from PC-MSCs effectively increased the level of miR-21 in the brain of AD mice. Additionally, replenishment of miR-21 restored the cognitive deficits in APP/PS1 mice and prevented pathologic features. Taken together, these findings suggest that exosomes from PC-MSCs could improve the learning and memory capabilities of APP/PS1 mice, and that the underlying mechanism may lie in the restoration of synaptic dysfunction and regulation of inflammatory responses through regulation of miR-21.-Cui, G.-H., Wu, J., Mou, F.-F., Xie, W.-H., Wang, F.-B., Wang, Q.-L., Fang, J., Xu, Y.-W., Dong, Y.-R., Liu, J.-R., Guo, H.-D. Exosomes derived from hypoxia-preconditioned mesenchymal stromal cells ameliorate cognitive decline by rescuing synaptic dysfunction and regulating inflammatory responses in APP/PS1 mice.

Alzheimer's disease (AD) is the main form of dementia and has a steadily increasing prevalence. As both oxidative stress and metal homeostasis are involved in the pathogenesis of AD, it would be interesting to develop a dual function agent, targeting the two factors. Curcumin, a natural compound isolated from the rhizome of Curcuma longa , is an antioxidant and can also chelate metal ions. Whether the complexes of curcumin with metal ions possess neuroprotective effects has not been evaluated. Therefore, the present study was designed to investigate the protective effects of the complexes of curcumin with Cu(II) or Zn(II) on hydrogen peroxide (H₂O₂)-induced injury and the underlying molecular mechanisms. The use of rat pheochromocytoma (PC12) cells, a widely used neuronal cell model system, was adopted. It was revealed that curcumin-Cu(II) complexes systems possessed enhanced O₂ ·- -scavenging activities compared to unchelated curcumin. In comparison with unchelated curcumin, the protective effects of curcumin-Cu(II) complexes systems were stronger than curcumin-Zn(II) system. Curcumin-Cu(II) or -Zn(II) complexes systems significantly enhanced the superoxide dismutase, catalase, and glutathione peroxidase activities and attenuated the increase of malondialdehyde levels and caspase-3 and caspase-9 activities, in a dose-dependent manner. The curcumin-Cu(II) complex system with a 2:1 ratio exhibited the most significant effect. Further mechanistic study demonstrated that curcumin-Cu(II) or -Zn(II) complexes systems inhibited cell apoptosis via downregulating the nuclear factor κB (NF-κB) pathway and upregulating Bcl-2/Bax pathway. In summary, the present study found that curcumin-Cu(II) or -Zn(II) complexes systems, especially the former, possess significant neuroprotective effects, which indicates the potential advantage of curcumin as a promising agent against AD and deserves further study., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.