Chelator boosted tumor-retention and pharmacokinetic properties: development of 64Cu labeled radiopharmaceuticals targeting neurotensin receptor.

PURPOSE: Accumulating evidence suggests that neurotensin (NTS) and neurotensin receptors (NTSRs) play key roles in lung cancer progression by triggering multiple oncogenic signaling pathways. This study aims to develop Cu-labeled neurotensin receptor 1 (NTSR1)-targeting agents with the potential for both imaging and therapeutic applications. METHOD: A series of neurotensin receptor antagonists (NRAs) with variable propylamine (PA) linker length and different chelators were synthesized, including [64Cu]Cu-CB-TE2A-iPA-NRA ([64Cu]Cu-4a-c, i = 1, 2, 3), [64Cu]Cu-NOTA-2PA-NRA ([64Cu]Cu-4d), [64Cu]Cu-DOTA-2PA-NRA ([64Cu]Cu-4e, also known as [64Cu]Cu-3BP-227), and [64Cu]Cu-DOTA-VS-2PA-NRA ([64Cu]Cu-4f). The series of small animal PET/CT were conducted in H1299 lung cancer model. The expression profile of NTSR1 was also confirmed by IHC using patient tissue samples. RESULTS: For most of the compounds studied, PET/CT showed prominent tumor uptake and high tumor-to-background contrast, but the tumor retention was strongly influenced by the chelators used. For previously reported 4e, [64Cu]Cu-labeled derivative showed initial high tumor uptake accompanied by rapid tumor washout at 24 h. The newly developed [64Cu]Cu-4d and [64Cu]Cu-4f demonstrated good tumor uptake and tumor-to-background contrast at early time points, but were less promising in tumor retention. In contrast, our lead compound [64Cu]Cu-4b demonstrated 9.57 ± 1.35, 9.44 ± 2.38 and 9.72 ± 4.89%ID/g tumor uptake at 4, 24, and 48 h p.i., respectively. Moderate liver uptake (11.97 ± 3.85, 9.80 ± 3.63, and 7.72 ± 4.68%ID/g at 4, 24, and 48 h p.i.) was observed with low uptake in most other organs. The PA linker was found to have a significant effect on drug distribution. Compared to [64Cu]Cu-4b, [64Cu]Cu-4a had a lower background, including a greatly reduced liver uptake, while the tumor uptake was only moderately reduced. Meanwhile, [64Cu]Cu-4c showed increased uptake in both the tumor and the liver. The clinical relevance of NTSR1 was also demonstrated by the elevated tumor expression in patient tissue samples. CONCLUSIONS: Through the side-by-side comparison, [64Cu]Cu-4b was identified as the lead agent for further evaluation based on its high and sustained tumor uptake and moderate liver uptake. It can not only be used to efficiently detect NTSR1 expression in lung cancer (for diagnosis, patient screening, and treatment monitoring), but also has the great potential to treat NTSR-positive lesions once chelating to the beta emitter 67Cu.

The epidemiology of alcohol burns at a major burn centre in North China.

This study was designed to explore the epidemiological characteristics and potential preventive strategies of alcohol burns. In this five-year, retrospective study, 163 patients with alcohol burns (admitted from 1 January 2015 to 31 May 2020 were included. There was a male-to-female ratio of 1.1:1, a mean age of 34.1±16.8 years, and a mean burn size of 13.3±13.7% total body surface area (TBSA). The number of patients with alcohol burns was similar year by year during the five-year period. Just over half of patients (n=84, 51.5%) sustained a third-degree burn injury, which was significantly associated with a longer hospital stay and the need for surgery. The most prevalent aetiology was cupping (n=49, 29.5%), followed by cooking hotpot (n=37, 22.7%). Of the patients, seven (4.29%) sustained injuries during experiments at school and one patient sustained injury when using alcohol spray for disinfection against COVID-19. The incidence of facial burn injury (n=105, 64.4%) was significantly higher than previously reported data (33.2%). The result of the study showed that cupping and hotpot were the main causes of alcohol burns in Beijing, which should be taken into consideration for prevention. It is necessary to strengthen safety management of classes at school where experiments are undertaken and to educate the general public on the proper means of disinfecting against COVID-19.

Electrochemical Oxidation Enables Regioselective 1,3-Hydroxyfunctionalization of Cyclopropanes.

The direct construction of 1,3-hydroxyfunctionalized molecules is still a significant challenge, as they can currently be obtained through multiple synthetic steps. Herein, we report a general and efficient 1,3-hydroxyfunctionalization of arylcyclopropanes by electrochemical oxidation with a strategic choice of nucleophiles and H2O. 1,3-Amino alcohols, 1,3-alkynyl alcohols, 1,3-hydroxyesters, and 1,3-halo alcohols are achieved with high levels of chemo- and regio-selectivity, opening a new dimension for 1,3-difunctionalization reaction.

An innovated elastic compression hemostasis technique for extremity excision in patients with extensive burns: A prospective clinical randomized controlled trial.

OBJECTIVE: To introduce an innovative elastic compression hemostasis technique for extremity excision in extensively burnt patients and investigate its effectiveness. METHODS: Ten patients were included and divided into 2 groups: the control group (4 patients, 12 extremities) receiving the conventional hemostasis technique and the experimental group (6 patients, 14 extremities) receiving the innovative technique. General data of the patients were collected, excision size measured, hemostasis time recorded, average blood loss per 1% total body surface area of the excised wound calculated, incidence of subcutaneous hematoma and take rate determined. RESULTS: The 2 groups had no statistical difference in the baseline data. Average blood loss per 1% total body surface area of the excised wound in the upper and the lower extremities was (62.1 ± 11.5) mL and (35.6 ± 11.0) mL in the experimental group, significantly less than (94.3 ± 6.9) mL and (82.3 ± 6.2) mL in the control group; a reduction of 34.1% and 56.8% respectively. Hemostasis time in the upper and the lower extremities were (5.0 ± 0.7) min/1% total body surface area and (2.6 ± 0.3) min/1% total body surface area, respectively, in the experimental group, significantly less than (7.4 ± 0.6) min/1% total body surface area and (4.0 ± 0.9) min/1% total body surface area in the control group; a reduction of 31.8% and 34.9% respectively. The incidences of subcutaneous hematoma were 7.1% and 8.3%, and the take rate (85.9 ± 6.0)% and (86.5 ± 4.8)% in the experimental and the control group, respectively, with no statistically significant differences. CONCLUSION: The innovative elastic compression hemostasis technique is a reliable new method that significantly reduces blood loss during extremity excision in patients with extensive burns and is worth wider understanding and application.

Functional and aesthetic outcomes of abdominal full-thickness skin grafts in paediatric postburn digital and palmar flexion contractures.

The study aimed to assess the functional and aesthetic outcomes of abdominal full-thickness skin grafts (FTSGs) in paediatric postburn digital and palmar flexion contractures. The digital and palmar functions and aesthetics of 50 children who met the criteria were evaluated at pre-operation, the 3rd- and 12th-month post-operation, respectively. In the evaluation, the Vancouver Scar Scale (VSS), total active movement (TAM), and Jebsen-Taylor Hand Function Test (JHFT) were used. The contralateral, unaffected hand served as the criteria for functional recovery. The complications of donor sites were observed, and the take rate of skin grafts was calculated. The VSS scores at the 3rd and 12th months post-operation were lower than those before the operation. The TAM of each finger was improved at the 3rd and 12th months post-operation, compared with that before the operation. There was a significant difference in the time to complete the JHFT between the affected hand and the unaffected at the 3rd month post-operation, but no significant difference between them at the 12th month post-operation. The excellent and good take rate of the skin grafts was 90.00%.No donor site complications were observed. The abdominal FTSGs are effective in repairing paediatric digital and palmar scar contractures, with satisfying functional and aesthetic results, especially in large defects after scar release and resection.

Characteristics and aetiology of low-temperature burns in Beijing of China.

This study was designed to analyse the characteristics and aetiology of low-temperature burns and explore the prevention and treatment strategies. In total, 206 patients hospitalised with low-temperature burns in a major burn center in Beijing from 2017 to 2021 were included. There were 35-49 cases per year, with an average of 41 ± 4.5 cases. The prevalence of low-temperature burns was higher in female than in male and are mainly resulted from two kinds of incidents: unintended burns from heat treatment (50.97%, 105/206) and improper use of heating devices to keep warm (43.69%, 90/206). Most cases occurred in autumn (33.01%, 68/206) and the least in spring (17.96%, 37/206); cases in summer (24.27%, 50/206) and winter (24.76%, 51/206) accounted for nearly a quadrant respectively. Low-temperature burns in summer were mainly unintended burns from heat treatment (80%, 40/50), whereas in autumn were mainly resulted from improper use of heating devices to keep warm (55.88%, 38/68), the difference was statistically significant (χ2  = 42.801, P < .001). Of all the cases, the burn size ranged from 0.2% to 5% TBSA, mostly less than 1% (85.92%, 177/206); third-degree burns accounted for 98.54% (203/206). Patients admitted after 3 weeks post-injury accounted for 42.23% (87/206). All patients were cured, and most of them were by surgeries (70.87%, 146/206). The results of the study show that low-temperature burn injury features a predictable morbidity among different seasons, a higher prevalence in adult women and a frequent occurrence at home. The wounds of low-temperature burns are often small in size but deep in depth, and can be easily misdiagnosed as superficial burns. However, most low-temperature burn wounds require surgical treatment. The study also suggests that based on the characteristics and aetiology of low-temperature burns, targeted prevention and treatment measures should be mapped out.

A novel skin grafting modality: prefabricated large sheet of postage-stamp autografts and allografts to repair extensive burn wounds; a prospective matched-control study.

BACKGROUND: The excessively long operative time has been the greatest barrier to the success of transplanting postage-stamp auto- and allografts directly and piece-by-piece onto extensive burn wounds. To solve this challenge, the authors present a novel grafting modality, that is, the prefabricated-large-sheet grafting that moves the labor-intensive and time-consuming process of grafts-positioning before grafting and thereby markedly shortens the operative time. METHODS: Twenty-one operations using the novel modality were performed on 11 patients with extensive deep burns. The grafting time using the novel modality was recorded and compared with that of the conventional piece-by-piece grafting. Eventually, the take rates of the two modalities were compared. RESULTS: All patients were healed and discharged. The average grafting time per unit area (100 cm2) of prefabricated-large-sheet grafting and piece-by-piece grafting were (0.41±0.09) min and (7.46±1.07) min, respectively, and the difference is statistically significant(P<0.001). The average take rate of the prefabricated sheets was (85.43±6.14)% and that of the piece-by-piece transplanted grafts was (87.29±5.23)% and there is no significant difference(P>0.05). CONCLUSIONS: The prefabricated-large-sheet grafting significantly reduces the intraoperative grafting time while ensures uniformity of the skin grafts and secures good outcomes, thereby making the intermingled transplantation of postage-stamp auto- and allografts, which has been an excellent modality per se but limited to repair small residual wounds, now feasible to repair extensive deep burn wounds. It is worth wider understanding and application in the treatment of extensive deep burns.

Platelet distribution width associated with short-term prognosis and cost in paediatrics with partial-thickness thermal burns: A retrospective comparative study.

Platelets exert important roles in burn wound healing and involving in inflammatory regulation and tissue repair. Platelet distribution width (PDW) is an indicator representing platelet morphology and activation. In this study, we try to evaluate the value of PDW in predicting short-term prognosis and cost of paediatrics with partial-thickness thermal burns. This retrospective study enrolled 73 children with partial-thickness thermal burns. The Ability of PDW to predict wound healing was evaluated by receiver operating characteristic (ROC) curve. All 73 patients were assigned into high and low PDW group according to optimal cut-off value from ROC curve. Associations between PDW and 2-weeks healing rate, time to wound healing, in-hospital cost and length of stay were evaluated. Furthermore, Univariate and multivariate logistic regression analysis were used to furtherly evaluate the significance of PDW in wound healing. We found that all baseline characteristics between groups were comparable (all P > .05). High PDW group had a significant higher 2-weeks wound healing rate than those with a low PDW (66.7% versus 32.6%, P < .01). Moreover, the mean time to wound healing of high PDW was obviously shorter than that of low PDW group (15.4 ± 10.1 vs 20.7 ± 10.9, P = .04). Univariate (OR: 0.24, 95%CI: 0.09-0.65, P < .01) and multivariate (OR: 0.15, 95CI%:0.05-0.52, P < .01) analysis confirmed PDW as an independent marker for wound healing. Patients in high PDW group had a significant lower medical burden than low PDW group, including in-hospital cost (13.7 ± 10.6 vs 21.9 ± 16.7, ×103RMB, P = .02) and length of stay (12.2 ± 8.8 vs 19.0 ± 10.8 days, P < .01). In conclusion, PDW can sever as a potential indictor to predict the short-term prognosis of paediatrics with partial thickness thermal burns.

The Imbalance of Mitochondrial Homeostasis of Peripheral Blood-Derived Macrophages Mediated by MAFLD May Impair the Walking Ability of Elderly Patients with Osteopenia.

Introduction: Many Asian cohort studies have shown that nonalcoholic fatty liver disease (NAFLD), now renamed as metabolic dysfunction-associated fatty liver disease (MAFLD), increases the risk of osteoporosis, yet the effect of MAFLD on elderly patients with osteopenia (OPe) has not been reported. Objective: This study aimed to explore the influence of MAFLD on the function of macrophages in patients with OPe. Methods: A total of 107 elderly OPe patients with or without MAFLD who visited the Huadong Hospital Affiliated to Fudan University (Shanghai, China) between January 1st, 2021, and September 30th, 2021, were evaluated for an interviewer-assisted questionnaire, as well as clinical and biological assessments. Results: Comparing two groups of elderly patients with the same bone mass level, we found that the six-minute walking distance (P = 0.012) and short physical performance battery (SPPB) score (P = 0.0029) of the elderly OPe patients with MAFLD are worse than those in OPe patients without MAFLD. Our results confirmed that the mitochondrial reactive oxygen species (mtROS) in peripheral blood of OPe patients with MAFLD was significantly higher than those without. We also observed the mitochondrial metabolism level of peripheral blood-derived macrophages in the included patients and peripheral blood macrophages in patients with MAFLD with more unbalanced mitochondrial dynamics of macrophages, more weakened mitochondrial respiratory capacity, and greater mitochondrial microstructure damage, when compared with the elderly patients without MAFLD. Conclusions: To conclude, our data revealed that MAFLD itself may aggravate the inflammatory state in elderly OPe people due to mitochondrial homeostasis imbalance of peripheral blood macrophages. Damaged monocyte-macrophages might trigger attenuation of the walking ability of OPe patients.

Four drug metabolism-related subgroups of pancreatic adenocarcinoma in prognosis, immune infiltration, and gene mutation.

We aimed to screen the drug metabolism-related subgroups of pancreatic adenocarcinoma (PAAD) and to study the prognosis, clinical features, immune infiltration, and gene mutation differences of different subtypes in PAAD patients. All 181 cases of PAAD samples and clinical characteristics data were downloaded from The Cancer Genome Atlas (TCGA). After matching the drug metabolism-related genes downloaded from PMID 33202946 with the TCGA dataset, the drug metabolism-related genes were initially obtained. Besides, univariate Cox regression analysis was used to screen the drug metabolism genes related to the prognosis of PAAD. Moreover, the construction of the protein-protein interaction (PPI) network and gene ontology were performed. The four subgroups of PAAD obtained from unsupervised clustering analysis were systematically analyzed, including prognostic, GSVA, immune infiltration, and gene mutation analysis. A total of 83 drug metabolism genes related to the prognosis of PAAD were obtained and enriched in 16 pathways. The PPI network was composed of 248 relationship pairs. Four subgroups that can identify different subtypes of PPAD were obtained, and there were significant differences in survival and clinical characteristics, mutation types, and immune infiltration abundance between subgroups. A total of 17 different pathways among the four subgroups involved in cell cycle, response to stimulants such as drugs, and transmembrane transport. In this study, the four subgroups related to the drug metabolism of PAAD were comprehensively analyzed, and the important role of drug metabolism-related genes in the immune infiltration and prognosis of PAAD were emphasized.

GC6mA-Pred: A deep learning approach to identify DNA N6-methyladenine sites in the rice genome.

MOTIVATION: DNA N6-methyladenine (6mA) is a pivotal DNA modification for various biological processes. More accurate prediction of 6mA methylation sites plays an irreplaceable part in grasping the internal rationale of related biological activities. However, the existing prediction methods only extract information from a single dimension, which has some limitations. Therefore, it is very necessary to obtain the information of 6mA sites from different dimensions, so as to establish a reliable prediction method. RESULTS: In this study, a neural network based bioinformatics model named GC6mA-Pred is proposed to predict N6-methyladenine modifications in DNA sequences. GC6mA-Pred extracts significant information from both sequence level and graph level. In the sequence level, GC6mA-Pred uses a three-layer convolution neural network (CNN) model to represent the sequence. In the graph level, GC6mA-Pred employs graph neural network (GNN) method to integrate various information contained in the chemical molecular formula corresponding to DNA sequence. In our newly built dataset, GC6mA-Pred shows better performance than other existing models. The results of comparative experiments have illustrated that GC6mA-Pred is capable of producing a marked effect in accurately identifying DNA 6mA modifications.

Long wavelength emission fluorescent probe for highly selective detection of cysteine in living cells.

We developed a fluorescent probe, named 2-(4-(acryloyloxy) phenyl)-4-(2-carboxyphenyl)-7-(diethylamino) chromenylium (PA-A), for detecting Cys using the -OH protection/deprotection strategy, which can react with Cys to form a red-emitting anthocyanidin derivative fluorophore. The probe has high selectivity to Cys over Hcy and GSH in phosphate buffer solution (PBS, 10 mM, pH = 7.4), high sensitivity, a low detection limit of 4.48 × 10-8 mol/L, and it can be recognized with the naked eye. Fluorescence imaging experiment of Cys with PA-A at the cellular successfully showed excellent tissue penetration.

Early childhood development and parental training interventions in rural China: a systematic review and meta-analysis.

INTRODUCTION: Inadequate care during early childhood can lead to long-term deficits in skills. Parenting programmes that encourage investment in young children are a promising tool for improving early development outcomes and long-term opportunities in low-income and middle-income regions, such as rural China. METHODS: We conducted a systematic review and a meta-analysis to investigate the prevalence of early developmental delays and stimulating parenting practices as well as the effect of parental training programmes on child development outcomes in rural China. We obtained data in English from EconPapers, PubMed, PsycARTICLES, Cochrane Library, Web of Science and Scopus (Elsevier) and in Chinese from China National Knowledge Infrastructure, Wanfang Data and VIP Information. We conducted frequentist meta-analyses of aggregate data and estimated random-effects meta-regressions. Certainty of evidence was rated according to the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: We identified 19 observational studies on the prevalence of developmental delays and stimulating parenting practices for children under 5 years of age (n=19 762) and ten studies on the impact of parental training programmes on early child development (n=13 766). Children's risk of cognitive, language and social-emotional delays in the rural study sites (covering 14 provinces mostly in Central and Western China) was 45%, 46%, and 36%, respectively. Parental training programmes had a positive impact on child cognition, language and social-emotional development. CONCLUSION: There is evidence to suggest that early developmental delay and the absence of stimulating parenting practices (ie, reading, storytelling and singing with children) may be prevalent across rural, low-income and middle-income regions in Central and Western China. Results support the effectiveness of parental training programmes to improve early development by encouraging parental engagement. TRIAL REGISTRATION NUMBER: This study was registered with PROSPERO (CRD42020218852).

Use of Fresh Scalp Allografts From Living Relatives for Extensive Deep Burns in Children: A Clinical Study Over 7 Years.

Conventionally, pediatric patients with major burns need frozen cadaveric allografts to save their lives. However, these allografts are insufficient in many burn units because of cultural and local governmental laws in China. This paper reported 22 pediatric patients with major burns who received fresh scalp allografts from their parents, siblings, or relatives from January 2011 to December 2017. These 22 pediatric patients sustained deep partial-thickness to full-thickness burns involving 40% total body surface area (TBSA) on average. Wounds were covered with fresh scalp allografts alone or with postage stamp autografts and fresh scalp allografts post excision. Data were collected from medical files of the treated patients, including sex, age, etiology of burn injury, abbreviated burn severity index (ABSI), and TBSA. Postoperative variables included early survival rate of skin grafts, mean time to rejection, length of hospital stay (LHS), healing time of donor sites, and follow-up complications of donors. The 1-year survival rate of the 22 pediatric patients included into the study was 100%. The early survival rate of the scalp allografts was similar to the autografts. The mean time to rejection was 15.5 ± 3.60 days. The average LHS was 58 days. All donor sites healed within 7.6 days on average, without scar formation, alopecia areata, or folliculitis. Following up data of the donors revealed a full psychological sense of accomplishment and no regrets of donating the scalp to save the burned children. Therefore, the use of fresh scalp allografts is a feasible alternative to save pediatric patients with major burns when frozen allografts are unavailable.

Mechanism and prevention of facial pressure injuries: A novel emergent strategy supported by a multicenter controlled study in frontline healthcare professionals fighting COVID-19.

Numerous healthcare professionals fighting COVID-19 worldwide are suffering from the protective respirators related facial pressure injuries. This study explored the mechanism and prevention of such injuries and devised a novel emergent strategy, which was supported by a multicenter self-controlled study in 1161 frontline healthcare professionals. In this study, according to the anatomy of the face and the characteristics of facial pressure injuries, a respirator liner was designed using a polyurethane foam to redistribute the pressure across the face. A preclinical crossover trial was performed on eight participants to evaluate its efficacy. The strategy was then widely applied among 11 100 healthcare workers in seven frontline hospitals, and 1161 of them were sampled for a questionnaire investigation. The preclinical crossover trial showed that the novel strategy was very effective in preventing facial pressure injuries. The questionnaire investigation showed that pain score, wearing disturbance, and the incidence of pressure injury in the healthcare professionals were significantly correlated with wearing time (all ρ = 0.986). The new strategy significantly reduced the incidence of pressure injury from 84.7% to 11.1%, pain score IQR from 5 (2) to 1 (2), and wearing disturbance rate from 91.6% to 6.3%, and the results analyzed according to individual hospitals or different wearing time showed similar trends (all P < .0005). The protective respirators related facial pressure injuries can be effectively mitigated with this emergent strategy, which has also been applied in some European hospitals and can be popularized to help more healthcare professionals who are combating COVID-19 on the frontlines.

RXH-Reactive 18F-Vinyl Sulfones as Versatile Agents for PET Probe Construction.

Efficient radiolabeling reactions are important chemical tools in biomedical research especially in probe construction. Herein, three 18F-labeled vinyl sulfones were prepared. In particular, 18F-PEG1-VS (((2-(2-(fluoro-18F)ethoxy)ethyl)sulfonyl)ethane) could not only allow chemoselective labeling of bioactive molecules containing -XH (X = S, NH) groups, but also react with red blood cells both in vitro and in living mice for potential cell tracking applications. In addition, these hydrophilic agents were found to cross the blood brain barrier (BBB) efficiently and localize at the cerebellum region. In summary, 18F-labeled vinyl sulfones provide a versatile platform for PET probe construction.

A Bioinformatics Tool for the Prediction of DNA N6-Methyladenine Modifications Based on Feature Fusion and Optimization Protocol.

DNA N6-methyladenine (6mA) is closely involved with various biological processes. Identifying the distributions of 6mA modifications in genome-scale is of great significance to in-depth understand the functions. In recent years, various experimental and computational methods have been proposed for this purpose. Unfortunately, existing methods cannot provide accurate and fast 6mA prediction. In this study, we present 6mAPred-FO, a bioinformatics tool that enables researchers to make predictions based on sequences only. To sufficiently capture the characteristics of 6mA sites, we integrate the sequence-order information with nucleotide positional specificity information for feature encoding, and further improve the feature representation capacity by analysis of variance-based feature optimization protocol. The experimental results show that using this feature protocol, we can significantly improve the predictive performance. Via further feature analysis, we found that the sequence-order information and positional specificity information are complementary to each other, contributing to the performance improvement. On the other hand, the improvement is also due to the use of the feature optimization protocol, which is capable of effectively capturing the most informative features from the original feature space. Moreover, benchmarking comparison results demonstrate that our 6mAPred-FO outperforms several existing predictors. Finally, we establish a web-server that implements the proposed method for convenience of researchers' use, which is currently available at http://server.malab.cn/6mAPred-FO.

Circular RNA circ-EGLN3 promotes renal cell carcinoma proliferation and aggressiveness via miR-1299-mediated IRF7 activation.

Renal cell carcinoma (RCC) is a highly lethal cancer with increasing incidence worldwide. The purpose of the present study was to investigate the functions and molecular mechanisms of circular RNA (circRNA), circ-EGLN3, in RCC progression. The expression levels of circ-EGLN3 were assessed by a quantitative real-time polymerase chain reaction. Kaplan-Meier analysis was applied to uncover the prognostic role of circ-EGLN3 in patients with RCC. Cell viability was analyzed using cell counting kit-8 and cell apoptosis was assessed using flow cytometric experiment. Cell migratory and invasive abilities were determined by wound scratch and transwell experiments. Subcellular distribution detection was utilized to investigate the location of circ-EGLN3. Dual-luciferase reporter test was utilized for identifying the molecular mechanism of circ-EGLN3. The results indicated that circ-EGLN3 was elevated in RCC tissues and cell lines and predicted unfavorable prognosis for the patients with RCC. Silenced circ-EGLN3 hindered cell proliferation, migration, and invasion but facilitated apoptosis of RCC cells. Ectopic expressed circ-EGLN3 induced the opposite effects mentioned above. Mechanistically, circ-EGLN3 was mainly located at the cytoplasm. Circ-EGLN3 acted as a competing endogenous RNA (ceRNA) to enhance the IRF7 level via sponging miR-1299. Moreover, circ-EGLN3 mediated elevation of IRF7 is responsible for RCC cell proliferation and aggressiveness. Collectively, our study suggested that circ-EGLN3 knockdown suppressed RCC progression through acting as a ceRNA to regulate the IRF7 expression by targeting miR-1299. Circ-EGLN3 might be a potential therapeutic target for RCC management.

Bionic Preparation of CeO2-Encapsulated Nitrogen Self-Doped Biochars for Highly Efficient Oxygen Reduction.

This study reports the superior performance of novel carbonaceous materials, CeO2-encapsulated nitrogen-doped biochars [BC-Ce-X (X = 1 and 2)], for oxygen reduction reaction (ORR). The biomass precursor of this value-added biochar material was biomimetically prepared via a hydroponic operation in the Ce-enriched solution. The characterization results showed that CeO2 with large amounts of oxygen vacancies was stably embedded in the N self-doped biochars during the pyrolytic processes. The measured specific surface areas of cerium-free biochar (BC sample), BC-Ce-1, and BC-Ce-2 were 79, 566, and 518 m2/g, respectively. The BC-Ce-X (X = 1 and 2) showed excellent ORR performances with onset potentials of ∼0.90-0.91 V, which outperformed the commercial 10 wt % Pt/C and BC. Compared with Pt/C, the BC-Ce-2 had better methanol tolerance and stability. Also, BC-Ce-2 displayed excellent electrochemical activity for Zn/air batteries. Controlled experiments and density functional theoretical calculations illustrated the synergistic effect between the pyri-N/C centers and CeO2 with oxygen vacancies in ORR. The Lewis base sites, created by pyri-N and oxygen vacancies, greatly facilitated the chemisorption of O2 molecules.

SNX6 predicts poor prognosis and contributes to the metastasis of pancreatic cancer cells via activating epithelial-mesenchymal transition.

Pancreatic cancer remains a challenging disease with an overall cumulative 5-year survival rate around 6%. Though significant progress has been made in the availability of diagnostic techniques and treatment strategies, pancreatic cancer remains a disease of high mortality rate. Therefore, there is an urgent need for a better understanding of the molecular mechanisms that governs the oncogenesis and metastasis process of pancreatic cancer. In the present study, by using the Cancer Genome Atlas (TCGA) dataset analysis, we demonstrated that sorting nexin 6 (SNX6) serves as a biomarker for predicting prognosis of pancreatic cancer. In vitro studies demonstrated that silencing of SNX6 expression reduced cell proliferation, colony formation, invasion, and metastasis. Higher level of SNX6 helps maintain the mesenchymal properties, which renders migration and invasive capacities to pancreatic cancer cells. Moreover, in the process of TGF-ß-induced epithelial to mesenchymal transition (EMT), the expression level of SNX6 was increased, and silencing of SNX6 expression could inhibit the TGF-ß-induced EMT program. These results collectively uncovered a novel predictive marker for pancreatic cancer and provided the possible underlying molecular mechanism.