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Creating oxide interfaces with precise chemical specificity at the atomic layer level is desired for the engineering of quantum phases and electronic applications, but highly challenging, owing partially to the lack of in situ tools to monitor the chemical composition and completeness of the surface layer during growth. Here we report the in situ observation of atomic layer-by-layer inner potential variations by analysing the Kikuchi lines during epitaxial growth of strontium titanate, providing a powerful real-time technique to monitor and control the chemical composition during growth. A model combining the effects of mean inner potential and step edge density (roughness) reveals the underlying mechanism of the complex and previously not well-understood reflection high-energy electron diffraction oscillations observed in the shuttered growth of oxide films. General rules are proposed to guide the synthesis of atomically and chemically sharp oxide interfaces, opening up vast opportunities for the exploration of intriguing quantum phenomena at oxide interfaces.

The aim of this study is to perform proteomic and metabolomic analyses in bilateral renal pelvis urine of patients with unilateral uric acid kidney stones to identify the specific urinary environment associated with uric acid stone formation. Using cystoscopy-guided insertion of ureteral catheters, bilateral renal pelvis urine samples are collected. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is employed to identify differentially expressed proteins and metabolites in the urine environment. Differentially expressed proteins and metabolites are further analyzed for their biological functions and potential metabolic pathways through Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In the urine from the stone-affected side, eight differential proteins were significantly upregulated, and six metabolites were dysregulated. The uric acid stone urinary environment showed an excess of α-ketoisovaleric acid and 3-methyl-2-oxovaleric acid, which may contribute to the acidification of the urine. Functional and pathway analyses indicate that the dysregulated metabolites are mainly associated with insulin resistance and branched chain amino acid metabolism., (© 2024. The Author(s).)

Objective: To develop a comprehensive framework for selecting outcomes in evaluating the clinical efficacy of Chinese herbal injections and to scientifically select outcomes for the clinical randomized controlled trial (RCT) of Tan-Re-Qing injection intervening AECOPD., Methods: A comprehensive literature review and consensus methods, including focus groups and Delphi surveys, were utilized., Results: Literature analysis identified 513 publications, encompassing regulatory guidance, guidelines, expert consensus, and RCTs. Initial dimensions include clinical efficacy, safety, and health economics. Primary outcomes should align with study objectives. Recommended evaluation domains include death, treatment outcome, future impact, quality of life, and safety. Commonly recommended outcomes comprise mortality, arterial blood gases, CAT, exacerbation frequency, adverse events, and lung function. Network meta-analysis identified specific therapeutic efficacy markers (white blood cell count, IL-6, IL-8). Quality of life assessment recommended SF-12, EQ-5D, or CAT. Emphasis on AECOPD frequency and lung function was noted. Delphi survey yielded 41 outcomes across various domains for evaluating Tan-Re-Qing in AECOPD., Conclusion: The findings contribute to developing a robust and reliable trial design for Tan-Re-Qing injection in AECOPD. The methodology employed in this study ensures a systematic and comprehensive approach to the selection of outcomes for the clinical evaluation of future studies in this field.

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Tian-Wei Zhang, Li Xing, Jun-Long Tang, Jing-Xiao Lu, Chun-Xiao Liu. Marchantin M Induces Apoptosis of Prostate Cancer Cells Through Endoplasmic Reticulum Stress. Med Sci Monit, 2015; 21: 3570-3576. DOI: 10.12659/MSM.894476.

The environmental pollution and health hazards caused by the extensive use of organophosphorus flame retardants (OPFRs) have become a problem of wide concern around the world. As a typical OPFR, 2-ethylhexyl diphenyl phosphate (EHDPP) can be detected in water, atmosphere, soil and other environmental media. It widely exists in production and life and can accumulate in organisms, causing great risks the ecosystem and human health. This paper reviews the research of EHDPP domestically and abroad, and summarizes the physicochemical properties of EHDPP and the population situation of occupational exposure, environmental exposure, and population exposure in recent years. Besides, it summarizes the toxic effects and mechanisms of EHDPP, including acute toxicity, hepatotoxicity, neurotoxicity, reproductive and developmental toxicity, and carcinogenesis effects. This paper also proposes the future direction of toxicity and health risks of EHDPP, which provides a theoretical basis for further research on environmental hazards and safety evaluation of EHDPP.

Background: The use of 3D-printed pelvic prosthesis for postoperative reconstruction after pelvic tumor resection has become one of the primary reconstruction methods the incidence of complications related to postoperative prosthesis reconstruction is high. Drawing on the failure of the type of bone tumor reconstruction in Henderson,the occurrence of postoperative complications was explored to take advantage of the design improvement of the 3D-printed prosthesis of subsequent pelvic tumors., Methods: The data for patients who underwent 3D-printed pelvic tumor prostheses in the Department of Bone and Soft Tissue Surgery at the Affiliated Cancer Hospital of Guangxi Medical University from January 2019 to October 2022 were collected and analyzed., Results: The median follow-up time for all patients was 15.99 months (1.33-31.16 months). At the most recent follow-up,all patients were alive,with an average Musculoskeletal Tumor Society (MSTS) score of 21.46 (17 to 26 points). Local recurrence occurred in two cases (15.3%), metastasis in four cases (30.7%), and complications in 10 cases (76.9%). Early complications after surgery were primarily local wound fissure, deep tissue infection, and postoperative neuralgia. Later complications included loose dissolution of internal fixation, postoperative prosthetic dislocation, and postoperative gluteal middle muscle gait., Conclusion: 3D printing personalized design pelvic tumor prosthesis is an effective way to reconstruct, and designing pelvic 3D printed tumor prosthesis with the help of Henderson's bone tumor reconstruction failure concept may help bone tumor surgeons develop better pelvic tumor prosthesis., 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 © 2023 Liu, Yang, Zhang, Tan and Yuan.)

Highland barley, also called "qingke" in Tibetan, is mainly cultivated in the Tibetan Plateau of China and has been used as a major staple food for Tibetans. Recently, Fusarium head blight (FHB) of qingke was frequently observed around the Brahmaputra River in Tibet. Considering the importance of qingke for Tibetans, the assessment of Fusarium mycotoxin contamination is essential for food safety. In this study, a total of 150 freshly harvested qingke grain samples were obtained from three regions around the Brahmaputra River in Tibet (China) in 2020. The samples were investigated for the occurrence of 20 Fusarium mycotoxins using high-performance liquid chromatography-tandem mass spectrometry (HPLC‒MS/MS). The most frequently occurring mycotoxin was enniatin B (ENB) (46%), followed by enniatin B 1 (ENB 1 ) (14.7%), zearalenone (ZEN) (6.0%), enniatin A 1 (ENA 1 ) (3.3%), enniatin A (ENA) (1.3%), beauvericin (BEA) (0.7%), and nivalenol (NIV) (0.7%). Due to the increase in altitude, the cumulative precipitation level and average temperature decreased from the downstream to the upstream of the Brahmaputra River; this directly correlated to the contamination level of ENB in qingke, which gradually decreased from downstream to upstream. In addition, the level of ENB in qingke obtained from qingke-rape rotation was significantly lower than that from qingke-wheat and qingke-qingke rotations (p < 0.05). These results disseminated the occurrence of Fusarium mycotoxins and provided further understanding of the effect of environmental factors and crop rotation on Fusarium mycotoxins., (© 2023. The Author(s) under exclusive licence to Society for Mycotoxin (Research Gesellschaft für Mykotoxinforschung e.V.) and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Although the current conventional treatment strategies for esophageal carcinoma (EC) have been proven effective, they are often accompanied by serious adverse events. Therefore, it is still necessary to continue to explore new therapeutic strategies for EC to improve the clinical outcome of patients., Aim: To elucidate the clinical efficacy of concurrent chemoradiotherapy (CCRT) with thalidomide (THAL) and S-1 (tegafur, gimeracil, and oteracil potassium capsules) in the treatment of EC as well as its influence on serum tumor markers (STMs)., Methods: First, 62 patients with EC treated at the Zibo 148 Hospital between November 2019 and November 2022 were selected and grouped according to the received treatment. Among these, 30 patients undergoing CCRT with cis-platinum and 5-fluorouracil were assigned to the control group (Con), and 32 patients receiving CCRT with THAL and S-1 were assigned to the research group (Res). Second, inter-group comparisons were carried out with respect to curative efficacy, incidence of drug toxicities, STMs [carbohydrate antigen 125 (CA125) and macrophage inflammatory protein-3α (MIP-3α)], angiogenesis-related indicators [vascular endothelial growth factor (VEGF); VEGF receptor-1 (VEGFR-1); basic fibroblast growth factor (bFGF); angiogenin-2 (Ang-2)], and quality of life (QoL) [QoL core 30 (QLQ-C30)] after one month of treatment., Results: The analysis showed no statistical difference in the overall response rate and disease control rate between the two patient cohorts; however, the incidences of grade I-II myelosuppression and gastrointestinal reactions were significantly lower in the Res than in the Con. Besides, the post-treatment CA125, MIP-3α, VEGF, VEGFR-1, bFGF, and Ang-2 Levels in the Res were markedly lower compared with the pre-treatment levels and the corresponding post-treatment levels in the Con. Furthermore, more evident improvements in QLQ-C30 scores from the dimensions of physical, role, emotional, and social functions were determined in the Res., Conclusion: The above results demonstrate the effectiveness of THAL + S-1 CCRT for EC, which contributes to mild side effects and significant reduction of CA125, MIP-3α, VEGF, VEGFR-1, bFGF, and Ang-2 Levels, thus inhibiting tumors from malignant progression and enhancing patients' QoL., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Stereotactic ablative radiotherapy (SABR) has been increasingly used for the treatment of inoperable early-stage non-small cell lung cancer (NSCLC). It has been shown to provide promising local control (LC) and toxicity in prospective trials. However, randomized trials have shown conflicting results in terms of whether SABR confers an overall survival (OS) advantage compared to conventionally fractionated radiotherapy (CFRT). A systematic review of Medline and Embase (inception to December 2020) was performed on early-stage NSCLC patients randomized to SABR versus CFRT. Two independent reviewers screened titles, abstracts, and manuscripts. A random-effects model was used to estimate treatment effects. Toxicity outcomes were compared by the Cochran-Mantel-Haenszel test. Individual patient data were digitally approximated and pooled as secondary analysis. The literature search identified 1494 studies, and 16 studies were included for full-text review. Two randomized trials were identified, including a total of 203 patients, of which 115 (57%) received SABR, and 88 (43%) received CFRT. The weighted mean age was 74 years and 48% of patients were male. Most patients had T1 cancers (67%). Stereotactic ablative radiotherapy was not associated with a significant improvement in OS (hazard ratio: 0.84; 95% confidence interval (CI) 0.34-2.08, p=0.71). There was no significant difference in LC between SABR and CFRT (relative risk: 0.59; CI 0.28-1.23, p=0.16). Of the commonly reported adverse events, one grade 4 toxicity of dyspnea was reported for SABR, while all others i.e., grade 3 or higher toxicities were similar. Stereotactic ablative radiotherapy demonstrated less esophagitis, dyspnea, and skin reaction of any grade. Despite widespread adoption and extensive single-arm prospective and retrospective studies suggesting its benefit, this systematic review and meta-analysis of randomized trials fail to confirm improvements in LC, OS, and toxicity profile of SABR over CFRT in early NSCLC. This small study is likely underpowered to detect clinically significant differences., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2023, Mutsaers et al.)

Background: This study examined the postoperative follow-up attendance of oral squamous cell carcinoma (OSCC) patients, evaluated some of the factors associated with it, and assessed its relationship with early detection of postoperative disease progression., Methods: An exploratory retrospective cohort study of 430 OSCC patients was conducted. We examined associations of follow-up attendance within the first year after surgery with selected demographic and clinical factors, and with early detection of disease progression., Results: The mean number of follow-up visits within the first year after surgery was 3.9 out of the 12 recommended at our center; few patients were fully adherent. Age ≥70 years, unmarried status, high education level, and negative history of surgery for premalignant or malignant lesions from oral cavity or other sites were significantly associated with lower follow-up attendance. Greater follow-up attendance was significantly associated with early detection of disease progression during the first year after surgery (p = 0.025)., Conclusions: Adherence to follow-up visits was poor. Several sociodemographic and clinical factors were related to follow-up attendance, greater follow-up attendance was significantly associated with early detection of disease progression, and these should be further explored in future research., (© 2023 Wiley Periodicals LLC.)

Introduction: Neobladder urolithiasis is a rare but important delaying complication of orthotopic urinary diversion. We report a case of Hem-o-Lok (HOLC) migration into the neobladder with giant stone formation after orthotopic neobladder cystectomy., Case Report: We report a case of a 57-year-old man with frequent urination and occasional discharge of stones 3 years after a laparoscopic orthotopic neobladder cystectomy. Computed tomography revealed a large round 3.5 cm calculus. An endoscopic neocystolitholapaxy was performed, and a Hem-o-Lok was found in the center of the stone., Conclusion: We described the case presentation, treatment and analysis of etiology of stone formation to avoid such complication., (© 2023. The Author(s).)

This study investigates how proxy solicitation and director ownership jointly affect directors' career consequences in Taiwan. We report that assent votes partly arising from proxies without shareholder voice increase the likelihood of departure for directors with higher ownership in firms soliciting proxies, especially for busy directors. Since proxy votes do not build extra reputation, this generates no spillover effect for both non-busy and busy directors. Overall, we support the arguments based on prior studies that votes holding information on shareholder voice have implications on directors' careers. Furthermore, different board seats provide unequal incentives for busy directors., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Circadian rhythm (CR) disruption contributes to tumor initiation and progression, however the pharmacological targeting of circadian regulators reversely inhibits tumor growth. Precisely controlling CR in tumor cells is urgently required to investigate the exact role of CR interruption in tumor therapy. Herein, based on KL001, a small molecule that specifically interacts with the clock gene cryptochrome (CRY) functioning at disruption of CR, we fabricated a hollow MnO 2 nanocapsule carrying KL001 and photosensitizer BODIPY with the modification of alendronate (ALD) on the surface (H-MnSiO/K&B-ALD) for osteosarcoma (OS) targeting. The H-MnSiO/K&B-ALD nanoparticles reduced the CR amplitude in OS cells without affecting cell proliferation. Furthermore, nanoparticles-controlled oxygen consumption by inhibiting mitochondrial respiration via CR disruption, thus partially overcoming the hypoxia limitation for photodynamic therapy (PDT) and significantly promoting PDT efficacy. An orthotopic OS model demonstrated that KL001 significantly enhanced the inhibitory effect of H-MnSiO/K&B-ALD nanoparticles on tumor growth after laser irradiation. CR disruption and oxygen level enhancement induced by H-MnSiO/K&B-ALD nanoparticles under laser irradiation were also confirmed in vivo. This discovery first demonstrated the potential of CR controlling for tumor PDT ablation and provided a promising strategy for overcoming tumor hypoxia., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

The electrical microenvironment plays an important role in bone repair. However, the underlying mechanism by which electrical stimulation (ES) promotes bone regeneration remains unclear, limiting the design of bone microenvironment-specific electroactive materials. Herein, by simple co-incubation in aqueous suspensions at physiological temperatures, biocompatible regenerated silk fibroin (RSF) is found to assemble into nanofibrils with a β-sheet structure on MXene nanosheets, which has been reported to inhibit the restacking and oxidation of MXene. An electroactive hydrogel based on RSF and bioencapsulated MXene is thus prepared to promote efficient bone regeneration. This MXene/RSF hydrogel also acts as a piezoresistive pressure transducer, which can potentially be utilized to monitor the electrophysiological microenvironment. RNA sequencing is performed to explore the underlying mechanisms, which can activate Ca 2+ /CALM signaling in favor of the direct osteogenesis process. ES is found to facilitate indirect osteogenesis by promoting the polarization of M2 macrophages, as well as stimulating the neogenesis and migration of endotheliocytes. Consistent improvements in bone regeneration and angiogenesis are observed with MXene/RSF hydrogels under ES in vivo . Collectively, the MXene/RSF hydrogel provides a distinctive and promising strategy for promoting direct osteogenesis, regulating immune microenvironment and neovascularization under ES, leading to re-establish electrical microenvironment for bone regeneration., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Objective: To systematically evaluate the efficacy and safety of pembrolizumab (PD-1/PD-L inhibitor) and adjuvant chemotherapy to treat NSCLC and provide evidence-based reference for clinical use., Methods: By searching the Cochrane Library, EMBASE, PubMed, and Web of Science, according to the inclusion criteria, literature selection, data extraction, and quality evaluation were carried out for the included literature. The I 2 test was used to evaluate heterogeneity between studies, and the meta-analysis was performed using RevMan 5.3 software provided by Cochrane., Results: Finally, 14 relevant documents meeting the standards were included. It is a statistical difference in one-year survival rate [OR = 1.50, 95% CI (1.28, 1.76), P < 0.00001, I 2 = 0%, Z = 4.99]; overall response rate[OR =1.57, 95% CI (1.29, 1.90), P < 0.00001, I 2 = 0%, Z = 4.58]; progression-free survival [OR = 2.99, 95% CI (2.29, 3.91), P < 0.00001, I 2 = 26%, Z = 8.00]; and overall survival [OR = 1.38, 95% CI (1.07, 1.78), P = 0.01, I 2 = 46%, Z = 2.50] and reduces the incidence of adverse drug reactions [OR = 2.54, 95% CI (1.99, 3.25), P < 0.00001, I 2 = 69%, Z = 7.43]., Conclusion: Pembrolizumab adjuvant chemotherapy is effective in the treatment of advanced NSCLC, but attention should be paid to the occurrence of adverse reactions in clinical. Due to the limitations of the methodology included in the study, this conclusion required more validation of large-sample RCT., Competing Interests: We define that all authors have not been involved in a set of conditions affecting our professional judgment concerning the validity of research, and we are not influenced by financial gain., (Copyright © 2022 Wei-wei Guo et al.)

Extremely fast-charging lithium-ion batteries are highly desirable to shorten the recharging time for electric vehicles, but it is hampered by the poor rate capability of graphite anodes. Here, we present a previously unreported particle size and electrode porosity dual-gradient structure design in the graphite anode for achieving extremely fast-charging lithium ion battery under strict electrode conditions. We develop a polymer binder-free slurry route to construct this previously unreported type particle size-porosity dual-gradient structure in the practical graphite anode showing the extremely fast-charging capability with 60% of recharge in 10 min. On the basis of dual-gradient graphite anode, we demonstrate extremely fast-charging lithium ion battery realizing 60% recharge in 6 min and high volumetric energy density of 701 Wh liter -1 at the high charging rate of 6 C.

High-voltage spinel cobalt-free LiNi 0.5 Mn 1.5 O 4 (LNMO) is one of the most promising cathode candidates for next-generation lithium-ion batteries (LIBs) due to its high specific capacity, high operating voltage, and low cost. However, inferior electronic conductivity, transition metal dissolution, and fast capacity degradation of LNMO, especially in high mass loading for high areal capacity, are the critical material challenges for its practical application. Herein, trace multiple Cr-Fe-Cu elements doping of LiNi 0.45 Cr 0.0167 Fe 0.0167 Cu 0.0167 Mn 1.5 O 4 (CFC0.5-LNMO) cathode is achieved by a blow-spinning strategy to exhibit very stable cycling at a practical level of areal capacity up to 3 mAh cm -2 . It is demonstrated that the Cu, Fe, and Cr doping into the LNMO lattice can suspend the Mn dissolution and improve the Li ion diffusivity and electronic conductivity of the LNMO host. As a result, the obtained CFC0.5-LNMO cathode exhibits an excellent rate performance (1.75 mAh cm -2 at 1C) and long cycling stability under an areal capacity of 3 mAh cm -2 (78% capacity retention over 300 cycles at 0.5C)., (© 2022 Wiley-VCH GmbH.)

Poor immunogenicity and compromised T cell infiltration impede the application of immune-checkpoint blockade (ICB) immunotherapy for osteosarcoma (OS). Although autophagy is involved in enhancing the immune response, the synergistic role of autophagy in ICB immunotherapy and the accurate control of autophagy levels in OS remain elusive and challenging. Here, we designed a pH-sensitive autophagy-controlling nanocarrier, CUR-BMS1166@ZIF-8@PEG-FA (CBZP), loading a natural derivative, curcumin (CUR), to boost the immunotherapeutic response of PD-1/PD-L1 blockade by activating immunogenic cell death (ICD) via autophagic cell death, and BMS1166 to inhibit the PD-1/PD-L1 interaction simultaneously, enhancing the tumor immunogenicity and sensitizing the antitumor T cell immunity. After entering tumor cells, the pH-sensitive nanoparticles induced autophagy and decreased the intracellular pH, which in turn further facilitated the release of CUR to enhance autophagic activity. Transferring CBZP to orthotopic OS tumor-bearing mice showed powerful antitumor effects and established long-term immunity against tumor recurrence, accompanied by enhanced dendritic cell maturation and tumor infiltration of CD8 + T lymphocytes. Collectively, CBZP exhibited synergistic effects in treating OS by combining ICD induction with checkpoint blockade, thereby shedding light on the use of autophagy control as a potential clinical therapy for OS., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Night shift workers with disordered rhythmic mechanical loading are more prone to intervertebral disc degeneration (IDD). Our results showed that circadian rhythm (CR) was dampened in degenerated and aged NP cells. Long-term environmental CR disruption promoted IDD in rats. Excessive mechanical strain disrupted the CR and inhibited the expression of core clock proteins. The inhibitory effect of mechanical loading on the expression of extracellular matrix genes could be reversed by BMAL1 overexpression in NP cells. The Rho/ROCK pathway was demonstrated to mediate the effect of mechanical stimulation on CR. Prolonged mechanical loading for 12 months affected intrinsic CR genes and induced IDD in a model of upright posture in a normal environment. Unexpectedly, mechanical loading further accelerated the IDD in an Light-Dark (LD) cycle-disrupted environment. These results indicated that intrinsic CR disruption might be a mechanism involved in overloading-induced IDD and a potential drug target for night shift workers., (© 2021. The Author(s).)

Deguelin is a rotenoid of the flavonoid family, which can be extracted from Lonchocarpus, Derris, or Tephrosia. It possesses the inhibition of cancer cell proliferation by inducing apoptosis through regulating the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, the NF-κB signaling pathway, the Wnt signaling pathway, the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway and epidermal growth factor receptor (EGFR) signaling, activating the p38 mitogen-activated protein kinase (MAPK) pathway, repression of Bmi1, targeting cyclooxygenase-2 (COX-2), targeting galectin-1, promotion of glycogen synthase kinase-3β (GSK3β)/FBW7-mediated Mcl-1 destabilization and targeting mitochondria via down-regulating Hexokinases II-mediated glycolysis, PUMA-mediation, which are some crucial molecules which modulate closely cancer cell growth and metastasis. Deguelin inhibits tumor cell propagation and malignant transformation through targeting angiogenesis, targeting lymphangiogenesis, targeting focal adhesion kinase (FAK), inhibiting the CtsZ/FAK signaling pathway, targeting epithelial-mesenchymal transition (EMT), the NF-κB signaling pathway, regulating NIMA-related kinase 2 (NEK2). In addition, deguelin possesses other biological activities, such as targeting cell cycle arrest, modulation of autophagy, inhibition of hedgehog pathway, inducing differentiation of mutated NPM1 acute myeloid leukemia etc. Therefore, deguelin is a promising chemopreventive agent for cancer therapy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To examine the clinical features and prognostic value of TP53 mutation in circulating tumor DNA(ctDNA) of Chinese prostate cancer patients. Methods: A prospective cohort of 239 prostate cancer patients diagnosed in the Department of Urology, Fudan University Shanghai Cancer Center from May 2018 to June 2019 was included. The age of diagnosis was(65.4±7.6) years(range: 45 to 85 years). Clinical data were collected from patient diagnosis and treatment records as well as follow-up surveys. TP53 mutations in plasma were detected by target sequence capture and second-generation sequencing. The relationship between TP53 mutation status and progression-free survival(PFS) was analyzed in patients who received any treatment lines. Kaplan-Meier analysis was performed in different subgroups, survival curves were drawn, and Log-rank test was used for comparison. Cox regression models were used to estimate multivariate adjusted HR and 95 %CI associated with PFS. Results: In the cohort, 15.9%(38/239) patients had TP53 mutation. Patients with TP53 mutations had a higher rate of metastases initially diagnosed with prostate cancer (78.9% (30/38) vs. 60.2% (121/201), χ²=4.829, P= 0.028), as well as a higher rate of castration resistance (68.4% (26/38) vs. 42.8% (86/201), χ²=8.434, P= 0.004). Kaplan-Meier analysis revealed a median androgen-deprivation therapy-PFS of 13.0 months in patients with TP53 mutation and 17.0 months in patients with TP53 wild-type. The median abiraterone-PFS was 4.7 months for patients with TP53 mutation and 11.0 months for TP53 wild-type patients. The median docetaxel-PFS was 3.0 months in patients with TP53 mutation and 5.0 months in patients with TP53 wild-type. TP53 mutation was the undependent prognosis factor of PFS in patients treated with abiraterone( HR =2.23, 95 %CI : 1.26 to 3.94, P= 0.006) and docetaxel( HR =1.92, 95 %CI : 1.01 to 3.66, P= 0.047) had significant differences in PFS. Conclusions: TP53 mutations were associated with the presence of metastasis and castration resistance, and were also an independent prognostic factor for progression-free survival in patients treated with abiraterone and docetaxel.

Based on the standard method of dendrochronology, we examined the tree-ring width index of two dominant tree species in the Altay Mountains, China, including Picea obovata and Larix sibirica . We analyzed the basal area increments (BAI) of those two species and the relationships between their radial growth and the climatic factors, which were compared in similar habitats. The results showed that the BAI of P. obovata was greater than L. sibirica , but the radial growth rate of L. sibirica was greater. In recent 60 years, the radial growth of P. obovata negatively correlated with high temperature in the fast growing stage of previous year, while the high temperature in June of current year promoted the radial growth of L. sibirica. There was a significantly negative correlation between radial growth of L. sibirica with temperature in January of current year. The sensitivity of tree growth to climate showed an obvious increase after an abrupt climate change under the background of recent warming and wetting trend in mid-1980s. Results of the moving correlation analysis showed that the response of the radial growth of P. obovata and L. sibirica to temperature and precipitation were enhanced under the background of climate change in the study area.

We constructed standard tree-ring-width chronology of Picea likiangensis var. rubescens for the Larima sampling site in the Ganzi Prefecture, Sichuan Province, by the single-free detren-ding method. The results showed that there was significant and positive correlation between the tree-ring chronology and March-August 1-month scale standardized precipitation and evapotranspiration index (SPEI1) of Yajiang region. The variation of the March-August SPEI1 sequence for 1942-2008 was reconstructed based on the current and last year sequences of the tree-ring chronology, with an explained variation of 42.8%. The newly reconstructed series mainly represented the variation of SPEI1 in the low-frequency domain over the historical period. Three wet periods were found in 1442-1465, 1516-1601 and 1836-2008, while the two intervals were dry periods for the March-August SPEI1 reconstruction in the Yajiang region of West Sichuan Plateau. There was a significant drying trend in 1456-1762 for the reconstructed sequence, a significant wetting trend in 1455-1762, while the wetting trend was the most significant in 1959-2008. Mutation test showed that the sudden changes from dry to wet for the March-August SPEI1 reconstructions occurred in 1512, 1733, 1767, 1831, 1941, 1957 and 1975, while that in 1684 and 1961 was the opposite. The comparison with surrounding region showed a good coherence of variations in the low-frequency domain among the SPEI1 reconstruction for the Yajiang region, the annual precipitation reconstruction for the northeastern Tibetan Plateau, and the SPEI05 reconstruction for the northern slope of the eastern Qilian Mountains. The reconstructed sequence well represented the variation of the March-August SPEI1 in the northeastern Tibetan Plateau and the southern Qinhai Province.

Although autophagy may be beneficial for maintaining the metabolic balance of the extracellular matrix (ECM) in the nucleus pulposus (NP) and its vitality under inflammation, the underlying mechanism still remains unclear. A previous study found that autophagy activation stimulated the release of exosomes in normal chondrocytes, which are located in a similar avascular environment and share many common features with those of nucleus pulposus cells (NPCs). This study explored the protective effect on matrix degradation in the NP by exosomes derived from autophagy-activated NPCs and exosomal microRNAs. NPCs-derived exosomes (NPCs-Exos) were isolated from culture medium of either normal NPCs or rapamycin-treated NPCs and quantified by nanoparticle tracking analysis. The effect of rapamycin-treated NPC-derived exosomes on NPCs were assessed by coculture with interleukin 1β (IL-1β)-stimulated NPCs. After examination of six major proteinases of the ECM, matrix metalloproteinase 13 (MMP-13) was chosen for further study. miR-27a, which targets MMP-13, was investigated through previous studies and bioinformatics tool. The levels of miR-27a were upregulated in both rapamycin-treated NPCs and their exosomes, compared to the control. When exosomal miR-27a was transferred into NPCs, it alleviated IL-1β-induced degradation of the NPC ECM by targeting MMP-13. Autophagy activation may promote the release of NPCs-derived exosomes and thereby prevent the NPC matrix from degradation. Autophagy activation also alleviates intervertebral disc degeneration (IDD), at least partly via exosomal miR-27a, which restrains MMP-13 expression under IL-1β stimulation. Our work elucidates a new mechanism for how autophagy may participate in preventing IDD, which may be a promising therapeutic strategy., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Background: Exosomes may contain excess cellular components released by cells in response to harmful external stimuli to maintain cellular homeostasis. Inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), can induce cell apoptosis, alter cellular component expression levels, and stimulate exosome release. In this study, we examined whether exosomes released from nucleus pulposus cells (NPCs) under inflammatory conditions could induce normal NP cell apoptosis in rats and its underlining mechanism., Methods: Exosomes were isolated from TNF-α-treated NPCs and used to treat normal NPCs. The effects were assessed by flow cytometry and western blot analysis. Anti-apoptotic insulin-like growth factor-1 (IGF-1) expression in NPCs was assessed by western blot analysis. Given the exosomal miRNAs might be the key factors of exosomes, bioinformatics approaches and quantitative real-time polymerase chain reaction (qRT-PCR) were used to identify IGF-1-regulating micro RNAs (miRNAs), including miR-16. Luciferase reporter assay assessed miR-16 regulation of IGF-1 and IGF-1 receptor (IGF-1R). NPCs were transfected with miR-16 mimic, and exosomes were applied to normal NPCs. NPCs were pretreated with 10 ng/mL TNF-α, transfected with miR-16 inhibitors, and the exosomes were isolated. Cell and exosome miR-16 levels were detected by qRT-PCR. Western blot analysis determined IGF-1, IGF-1R, and apoptotic marker levels in exosome-treated NPCs., Results: Exosomes from TNF-α-treated NPCs induced apoptosis in normal NPCs and repressed IGF-1 expression. Exosomal miR-16 regulated IGF-1 and induced NPC apoptosis. The dual-luciferase reporter assay revealed that miR-16 binds the 3' untranslated regions (3'-UTRs) of IGF-1 and IGF-1R. Exosomal miR-16 repressed IGF-1 and the IGF-1R/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway which therefore induced NPC apoptosis. Rescue experiments using miR-16 inhibitors further validated these findings., Conclusions: The inflammatory factor TNF-α stimulated exosome release from NPCs, which induced the apoptosis of normal NPCs through the actions of exosomal miR-16. Exosomal miR-16 directly repressed the anti-apoptotic IGF-1/IGF-1R pathway, increasing the apoptosis of NPCs., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-227). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Decorin (Dcn) is a member of the class I small leucine-rich proteoglycans, whose expression in the nucleus pulposus (NP) of intervertebral discs (IVDs) has been shown to increase with aging in humans and sheep. Dcn induces autophagy in endothelial cells; however, its precise role in NP and IVD degeneration during aging is not well understood. We addressed this question in the present study by treating rat nucleus pulposus cells (NPCs) with different concentrations of Dcn. The Western blot analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling assay results showed that Dcn treatment induced autophagy and decreased apoptosis caused by interleukin (IL)-1β application. This effect was dependent on the protein kinase B/mechanistic target of rapamycin (mTOR)/p70 S6 kinase signaling. Dcn treatment also decreased the expression of matrix metalloproteinase-3 and -13 and decreased the IL-1β-induced attenuation of collagen type II and aggrecan levels. The role of Dcn in stimulating autophagy was further supported by the fact that the observed effects were abrogated by knocking down autophagy-related protein 7 with Atg7 small interfering RNA. Thus, Dcn protects NPCs in IVDs from IL-1β-induced apoptosis and degeneration by promoting autophagy through mTOR signaling., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Taking windfall woods of Picea schrenkiana in the southern mountainous area of the Ili Prefecture as the research object, tree-ring density chronologies were developed from the discs for maximum density (MXD), minimum density (MID), mean earlywood density (EWD), and mean latewood density (LWD) at five different stem heights (1.3, 5, 10, 15 and 20 m) to examine the climatic responses of tree-ring density by correlation analysis with local meteorological data. The results showed that there was a good coherence among the four types of tree-ring density chronologies for the same stem height, which was relatively significant for the data from 10, 15 and 20 m. The LWD had good coherence among different stem heights, while the climatic responses of tree-ring density at different stem heights varied. The MXD and LWD at 15 m were sensitive to mean tempera-ture from July to September in the previous year and from May to September in the current year. It might underestimate the response of P. schrenkiana to temperature if we sample tree-ring at 1.3 m.

Objective: To explore the value of the concentration of adenosine triphosphate (ATP) in CD4(+)T lymphocytes in predicting repeated respiratory tract infections (RRTI) in silicosis patients. Methods: In April 2020, 614 silicosis patients admitted from March 2016 to March 2018 were included in the study, and they were divided into the RRTI group ( n =105) and the non RRTI group ( n =509) according to whether the occurrence of RRTI, another 30 healthy cases taken from body check were served as control group, and the concentrations of ATP produced by CD4(+)T lymphocytes was measured by ImmuKnow assay, and were compared between the three groups. And drawed the receiver operating characteristic (ROC) curve, and the Logistic regression analysis was used to explore the risk factors of RRTI. Results: The incidence of RRTI in silicosis patients was 17.10% (105/614) . The concentration of ATP produced by CD4(+)T lymphocytes in the RRTI group [ (260.42±90.36) mg/L] was significantly lower than that in the non RRTI group [ (413.66±138.74) mg/L] ( t =-10.849, P <0.01) . The area under the ROC curve was 0.834, the cutoff value was 284 mg/L, the sensitivity was 0.88, and the specificity was 0.83. Logistic regression analysis showed that the concentration of ATP produced by CD4(+)T lymphocytes≤284 mg/L, impaired pulmonary ventilation function, serum albumin<40 g/L and diabetes were the risk factors of RRTI in silicosis patients ( OR =2.126, 1.217, 1.164, 1.125, P <0.05) . Conclusion: Low CD4(+)T lymphocyte ATP value was a risk factor of RRTI in silicosis patients, and can predict the risk of RRTI in patients with silicosis.

In recent years, the research of spatiotemporal clustering of disease is attracting more and more attention, which plays an important role in understanding the temporal and spatial distribution characteristics of diseases, and can provide references for the etiology exploration and prevention and control of diseases. In order to better understand the research methods of spatiotemporal clustering of diseases and its application progress, this paper summarizes the statistical methods commonly used in relevant researches at demestic and abroad from three aspects of temporal clustering, spatial clustering and spatiotemporal clustering of diseases.

Opinion Statement: Recent phase II clinical trials suggest that stereotactic ablative radiation therapy (SABR) can potentially improve survival for patients with oligometastatic cancer. However, these studies have mostly enrolled primaries other than gynecologic malignancies. While level I evidence is limited, recent publications exploring the use of SABR for oligometastatic gynecologic cancers have indicated a potential role for this treatment in para-aortic lymph node recurrences, and in visceral and brain metastases. The use of SABR for recurrences in the pelvis presents a number of challenges as these patients have often received previous radiation treatment. In these settings, care must be taken to avoid trespassing normal tissue tolerance with SABR leading to toxicity, especially as the potential benefit of SABR in this setting is not based on high-level evidence. Although SABR is feasible and in general safe for oligometastatic gynecologic malignancies, insufficient data are available to indicate whether it is associated with improved survival. Clinical judgment that incorporates patient and tumor factors is needed to determine if SABR is appropriate for selecting patients. Future directions include combining SABR with novel systemic therapies, determining optimal sequencing of treatments, and generating more robust randomized data pertaining to the use of SABR for oligometastatic gynecologic cancers.

Lithium cobalt oxide (LiCoO 2 ) possesses an attractive theoretical specific capacity (274 mAh g -1 ) and high discharge voltage (∼4.2 V vs Li + /Li). However, only a half of the theoretical capacity of LiCoO 2 is available in commercialized lithium ion batteries because of the intrinsic structural instability and detrimental interface of LiCoO 2 at the charging voltage over 4.2 V. Here, a facile blow-spinning synthetic method is developed to realize precise doping and simultaneous self-assembly coating of LiCoO 2 particles, achieving a record performance among present LiCoO 2 cathodes. Owing to the spatial confinement effect of microfibers fabricated by blow-spinning, homogeneously Mn and La doped in the LiCoO 2 host and uniformly Li-Ti-O segregated at the LiCoO 2 surface can be realized in every batch of samples. It is demonstrated that the Mn and La codoping can suspend the intrinsic instability and increase the Li + diffusivity of the LiCoO 2 host, and the Ti-based coating can stabilize the interface of LiCoO 2 particles at the charging voltage up to 4.5 V. As a result, the obtained comodified LiCoO 2 cathode shows the best rate performance (1.85 mAh cm -2 at 2C) and longest cycling stability under an areal capacity of 2.04 mAh cm -2 (83% capacity retention over 300 cycles at 0.3C), in comparison to previously reported LiCoO 2 cathodes.

There is one circadian clock in the central nervous system and another in the peripheral organs, and the latter is driven by an autoregulatory molecular clock composed of several core clock genes. The height, water content, osmotic pressure and mechanical characteristics of intervertebral discs (IVDs) have been demonstrated to exhibit a circadian rhythm (CR). Recently, a molecular clock has been shown to exist in IVDs, abolition of which can lead to stress in nucleus pulposus cells (NPCs), contributing to intervertebral disc degeneration (IDD). Autophagy is a fundamental cellular process in eukaryotes and is essential for individual cells or organs to respond and adapt to changing environments; it has also been demonstrated to occur in human NPCs. Increasing evidence supports the hypothesis that autophagy is associated with CR. Thus, we review the connection between CR and autophagy and the roles of these mechanisms in IDD.

The commercial ceramic nanoparticle coated microporous polyolefin separators used in lithium batteries are still vulnerable under external impact, which may cause short circuits and consequently severe safety threats, because the protective ceramic nanoparticle coating layers on the separators are intrinsically brittle. Here, a nacre-inspired coating on the separator to improve the impact tolerance of lithium batteries is reported. Instead of a random structured ceramic nanoparticle layer, ion-conductive porous multilayers consisting of highly oriented aragonite platelets are coated on the separator. The nacre-inspired coating can sustain external impact by turning the violent localized stress into lower and more uniform stress due to the platelet sliding. A lithium-metal pouch cell using the aragonite platelet coated separator exhibits good cycling stability under external shock, which is in sharp contrast to the fast short circuit of a lithium-metal pouch cell using a commercial ceramic nanoparticle coated separator., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To establish a series of three-dimensional measurement methods of nasolabial soft tissue for maxillary protrusion patients by using 3dMD camera, and to evaluate preoperative and postoperative changes of the nasolabial soft tissue., Methods: Three-dimensional facial photos of 30 female patients with maxillary protrusion [average age, (27.33±2.54) years] were taken by 3dMD camera preoperatively and at the end of postoperative 6 months or more. Then, 3dMD patient software was used to locate the selected landmarks at nasolabial region on the three-dimensional photos. Ten measurements, including soft tissue line distance, angle, curve distance and postoperative three-dimensional volume changes were measured twice with one week interval by 3 investigators, respectively. A standard consistency test calculated by the correlation coefficients (ICC) was performed between two sets of data (including all of the 10 measurements) for each investigator and among the three investigators to verify the repeatability., Results: The average maxillary incisor retraction distance of the 30 subjects was (5.13±0.99) mm, and the average follow-up time was (11.07±5.11) months. The standard consistency test was performed between the two sets of data for each investigator, and the correlation coefficients (ICC) of the 10 measurements were all over 0.8 for each investigator (P>0.05). The standard consistency test was performed among the three surveyors, with the result that the ICC of the width of the bilateral inner canthus, the height of the nose, the height of nasal tip, nasolabial angle, philtrum length, the curve height of upper vermilion and the height of upper lip were greater than 0.8 (P>0.05), and the ICC of the distance between SbalSbal, length of nasal dorsum and three-dimensional volume change of upper lip were 0.680, 0.627 and 0.528, respectively (P>0.05)., Conclusion: 3dMD camera and 3dMD patient software can be used to measure and analyze the three-dimensional morphology of the nasolabial soft tissue for patients with maxillary protrusion preoperatively and postoperatively, and it is relatively accurate and reliable. However, the repeatability of three-dimensional positioning of the nasal tip point and the Sbal is slightly worse resulting in the lower value of the ICC of the distance between SbalSbal and length of nasal dorsum, as well as the upper lip three-dimensional volume change after the operation.

Purpose: We examined whether female authorship, traditionally underrepresented in the radiation oncology (RO) literature, has improved during the past decade, and whether the introduction of double-blind peer review (where reviewers are blinded to author names and vice-versa) improved female authorship rates., Methods: We analyzed authorship lists during a 10-year period (2007-2016) from the 2 highest impact-factor RO journals: The International Journal of Radiation Oncology, Biology, Physics (IJROBP) and Radiotherapy and Oncology (R&O). From each journal, 20 articles per year were randomly selected. Gender trends of the first, second, last, and collaborating authors (defined as all other positions), were analyzed. A one-sample proportion test was used to compare US female senior authorship (2012-2016) with the 2015 benchmark for female US academic radiation oncologists (30.6%)., Results: Across 400 articles, the mean ± standard deviation percentage of female authors was 30.9% ± 22.0% with 34.8% of first, 36.7% of second, and 25.4% of last authors being female. The total percentage of female authors per year increased from 2007 to 2016 ( P = .005), with no significant increase in the percentage of first ( P = .250), second ( P = .063), or last ( P = .213) female authors. Double-blind peer review was associated with an increase in the mean percentage of female authors (2007-2011: 27.4% vs 2012-2016: 34.0%; P = .012). The proportion of US female senior authors in the latter period (27.6%) and the proportion of female US academic radiation oncologists (30.6%) were not significantly different ( P = .570)., Conclusions: Although the percentage of female authors in RO has increased during the past decade, this did not correspond to a higher representation of women in high-profile authorship positions. Introduction of double-blind peer review was associated with a rise in female authorship. The proportion of female US senior authors and academic radiation oncologists is similar, suggesting that senior authorship rates are approaching appropriate levels in the United States., (© 2019 The Author(s).)

Using highly dispersed metal fluoride nanoparticles to construct a uniform fluorinated alloy type interfacial layer on the surface of Li metal anodes is realized by an ex situ solution chemical modification method. The fluorinated alloy-type interfacial layer can effectively inhibit the growth of undesirable Li dendrites while enhancing the performance of Li metal anodes., (This journal is © The Royal Society of Chemistry 2019.)

Purpose: Some recent studies have suggested a relationship between cardiac dose and mortality in non-small cell lung cancer (NSCLC), but others have reported conflicting data. The goal of this study was to conduct a systematic review and meta-analysis to provide an evidence-based estimate of the relationship between cardiac dose and mortality in these patients., Methods and Materials: A systematic review of MEDLINE (PubMed) and Embase databases (inception to January 2018) was performed according to PRISMA guidelines. Studies that evaluated cardiac dosimetric factors in patients with NSCLC and included outcomes of cardiac events, cardiac mortality, and/or overall survival were identified., Results: From 5614 patients across 22 studies, a total of 214 cardiac dosimetric parameters (94 unique) were assessed as possible predictors of cardiac toxicity or death. Assessed predictors included general (eg, mean heart dose [MHD]), threshold-based (eg, heart V5), and anatomic-based (eg, atria, ventricles) dosimetric factors. The most commonly analyzed parameters were MHD, heart V5, and V30. Most studies did not make corrections for multiplicity of testing. For overall survival, V5 was found to be significant on multivariable analysis (MVA) in 1 of 11 studies and V30 in 2 of 12 studies; MHD was not significant in any of 8 studies. For cardiac events, V5 was found to be significant on multivariable analysis in 1 of 2 studies, V30 in 1 of 3 studies, and MHD in 2 of 4 studies. A meta-analysis of the data could not be performed because most negative studies did not report effect estimates., Conclusions: Consistent heart dose-volume parameters associated with overall survival of patients with NSCLC were not identified. Multiplicity of testing is a major issue and likely inflates the overall risk of type I errors in the literature. Future studies should specify predictors a priori, correct for multiplicity of testing, and report effect estimates for nonsignificant variables., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Two-dimensional (2D) boron nitride nanosheets (BNNSs) were chemically exfoliated from bulk boron nitride and coated onto the surface of a poly(ethylene oxide) (PEO)-based electrolyte through a dry-pressing transfer process. The fabricated BNNSs coating formed a robust interfacial layer to improve the chemical and mechanical stability of the PEO-based electrolyte, leading to the enhanced performance of solid-state Li metal batteries.

Objective: To study the relationship between Sonic hedgehog (Shh) associated single-nucleotide polymorphism (SNP) and non-syndromic cleft lip and/or palate (NSCL/P), and to explore the risk factors of cleft lip and/or palate. Many studies suggest that the pathogenesis of NSCL/P could be related to genes that control early development, in which the Shh signaling pathway plays an important role., Methods: Peripheral blood was collected from 197 individuals (100 patients with NSCL/P and 97 healthy controls). Haploview software was used for haplotype analysis and Tag SNP were selected, based on the population data of Han Chinese in Beijing of the international human genome haplotype mapping project. A total of 27 SNP were selected for the 4 candidate genes of SHH, PTCH1, SMO and GLI2 in the Shh signaling pathway. The genotypes of 27 SNP were detected and analyzed by Sequenom mass spectrometry. The data were analyzed by chi-squared test and an unconditional Logistic regression model., Results: The selected SNP basically covered the potential functional SNP of the target genes, and its minimum allele frequency (MAF) was >0.05: GLI2 73.5%, PTCH1 91.0%, SMO 100.0%, and SHH 75.0%. It was found that the genotype frequency of SNP (rs12674259) located in SMO gene and SNP (rs2066836) located in PTCH1 gene were significantly different between the NSCL/P group and the control group. Linkage disequilibrium was also found on 3 chromosomes (chromosomes 2, 7 and 9) where the 4 candidate genes were located. However, in the analysis of linkage imbalance haplotype, there was no significant difference between the disease group and the control group., Conclusion: In China, NSCL/P is the most common congenital disease in orofacial region. However, as it is a multigenic disease and could be affected by multiple factors, such as the external environment, the etiology of NSCL/P has not been clearly defined. This study indicates that Shh signaling pathway is involved in the occurrence of NSCL/P, and some special SNP of key genes in this pathway are related to cleft lip and/or palate, which provides a new direction for the etiology research of NSCL/P and may provide help for the early screening and risk prediction of NSCL/P.

Lithium metal is one of the most promising anode materials for high-energy-density Li batteries. However, low stability caused by dendrite growth and volume change during cycling hinders its practical application. Herein, we report an ingenious design of bio-inspired low-tortuosity carbon with tunable vertical micro-channels to be used as a host to incorporate nanosized Sn/Ni alloy nucleation sites, which can guide Li metal's plating/stripping and meanwhile accommodate the volume change. The pore sizes of the vertical channels of the carbon host can be regulated to investigate the structure-performance correlation. After compositing Li, the bio-inspired carbon host with the smallest pore size (∼14 μm) of vertical channels exhibits the lowest overpotential (∼18 mV at 1 mA cm -2 ), most stable tripping/plating voltage profiles, and best cycling stability (up to 500 cycles) in symmetrical cells. Notably, the carbon/Li composite anode is more rewarding than Li foil when coupled with LiFePO 4 in full cells, exhibiting a much lower polarization effect, better rate capability and higher capacity retention (90.6% after 120 cycles). This novel bio-inspired design of a low-tortuosity carbon host with nanoalloy coatings may open a new avenue for fabricating advanced Li-metal batteries with high performance., (© The Author(s) 2018. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Objective: To investigate the effects of basic fibroblast growth factor (bFGF) on healing of Mycobacterium tuberculosis infective wound in New Zealand rabbit after debridement. Methods: Thirty-two New Zealand rabbits (3 to 4 months old, no matter male or female) were intradermally injected with 0.1 mL of complete Freund's adjuvant on the buttocks. Six weeks later, each rabbit was injected with 0.5 mL 5×10(7) colony forming unit/mL Bacillus Calmette - Guerin on both sides of the back to reproduce the model of Mycobacterium tuberculosis infective wound in New Zealand rabbit. After successful modeling, the 32 rabbits were divided into growth factor (GF) group, antituberculosis drug (AD) group, combined treatment (CT) group, and blank control (BC) group according to the random number table, with 8 rabbits in each group. After a complete debridement, the wounds of rabbits in group GF were treated with recombinant bovine bFGF gel (300 IU/cm(2,) about 0.45 g for each wound), the wounds of rabbits in group AD were covered with gauze which was impregnated with 6 mL isoniazid injection and 0.15 g rifampicin powder-injection, the wounds of rabbits in group CT were covered with gauze which was impregnated with isoniazid injection and rifampicin powder-injection after being treated with recombinant bovine bFGF gel as before, the wounds of rabbits in group BC were covered with sterile gauze, with dressing change of once every two days until the wounds were completely healed. Immediately after surgery and on post surgery day (PSD) 7, 14, 21, and 28, the wounds of rabbits in each group were observed with naked eyes and photos. On PSD 7, 14, 21, and 28, the wound healing rate was calculated and the complete healing time of wound was recorded. On PSD 7, 14, 21, and 28, the tissue samples of wound edge were collected for histomorphological observation with hematoxylin and eosin staining and Masson staining. On PSD 21, the number of microvessels was counted with immunohistochemical method. On PSD 7, 14, 21, and 28, the content of hydroxyproline in wound edge was determined by enzyme-linked immunosorbent assay. The numbers of samples of above-mentioned experiments were all 8. Data were processed with analysis of variance for repeated measurement, analysis of variance of factorial design, one-way analysis of variance, least significant difference test and Bonferroni correction. Results: (1) The rabbits in four groups all survived to the end of experiment. Immediately after surgery, edema was observed in basal wounds of rabbits in the four groups. On PSD 7, the wounds of rabbits in the 4 groups were contracted with scabs and less edema. The wounds of rabbits in groups GF and CT became redder. On PSD 14, the wounds of rabbits in the 4 groups contracted obviously. There were no obvious exudates in wounds of rabbits in groups AD and CT, while 1 wound of rabbit in group GF and 2 wounds of rabbits in group BC became red and swelling with purulent exudates. On PSD 21, wounds of rabbits in groups GF and CT were basically healed, while 2 wounds of rabbits in group BC healed slowly with purulent secretion. On PSD 28, wounds of rabbits in the 4 groups were basically healed, while 2 wounds of rabbits in group BC hardly healed with redness and swelling. (2) From PSD 7 to 28, the wound healing rates of rabbits in groups GF, AD, and CT were significantly higher than those in group BC ( P <0.05). On PSD 14 and 21, the wound healing rates of rabbits in groups GF and CT were significantly higher than those in group AD ( P <0.05). From PSD 7 to 28, the wound healing rates of rabbits in group GF were close to those in group CT ( P >0.05). (3) The complete healing time of wounds of rabbits in groups GF, AD, and CT was significantly shorter than that in group BC ( P <0.05). The complete healing time of wounds of rabbits in groups GF and CT was significantly shorter than that in group AD ( P <0.05). The complete healing time of wounds of rabbits in group GF was close to that in group CT ( P >0.05). (4) On PSD 7, a large number of inflammatory cells infiltration were observed in wound tissue of rabbits in the 4 groups and a few epithelial cells were observed in wound tissue of rabbits in groups GF, AD, and CT. On PSD 14, more epithelial cells were observed in wound tissue of rabbits in groups GF and CT, and an obvious reduction of inflammatory cells infiltration was observed in wound tissue of rabbits in groups AD and CT. On PSD 21, there was a complete wound tissue structure and distinctive nuance of dyeing in wound tissue of rabbits in groups GF and CT while thinner new epithelium in wound tissue of rabbits in groups AD and BC, and inflammatory cell infiltration was observed in wound tissue of rabbits in group BC. On PSD 28, there was a complete wound tissue structure in wound tissue of rabbits in the 4 groups, the new epithelium in wound tissue of rabbits in groups GF, AD, and CT was thicker than that in group BC. (5) On PSD 7 and 14, the quantity of collagen fibers in wound tissue of rabbits in groups GF and CT was larger than that in the other two groups. On PSD 21, a large quantity of fibroblasts and well reorganized collagen fibers were observed in wound tissue of rabbits in groups GF and CT, a moderate quantity of fibroblasts and collagen fibers in a random arrangement were observed in wound tissue of rabbits in group AD, and a little quantity of fibroblasts and collagen fibers were observed in wound tissue of rabbits in group BC. On PSD 28, the quantity of collagen fibers in wound tissue of rabbits in the 4 groups was close to that of normal skin tissue, and the collagen fibers performed more well reorganized in wound tissue of rabbits in groups GF and CT. (6) On PSD 21, the numbers of microvessels per 200-time visual field in wound edge of rabbits in groups GF (31.6±1.2), AD (27.5±1.3), and CT (32.8±1.6) were significantly higher than the number in group BC (22.3±1.7, P <0.05). The numbers of microvessels in wound edge of rabbits in groups GF and CT were significantly higher than the number in group AD ( P <0.05). The number of microvessels in wound edge of rabbits in group GF was close to that in group CT ( P >0.05). (7) On PSD 7 and 28, there were no statistically significant differences in content of hydroxyproline in wound edge of rabbits in the 4 groups ( F =0.916, 1.752, P >0.05). On PSD 14 and 21, the content of hydroxyproline in wound edge of rabbits in groups GF, AD, and CT was significantly higher than that in group BC ( P <0.05). The content of hydroxyproline in the wound edge of rabbits in groups GF and CT was significantly higher than that in group AD ( P <0.05). The content of hydroxyproline in the wound edge of rabbits in group GF was close to that in group CT ( P >0.05). Conclusions: bFGF can be used solely or combined with AD to promote Mycobacterium tuberculosis infective wound healing in New Zealand rabbit after complete debridement of wound, which is better than single use of AD.

Ultrathick electrode design is a promising strategy to enhance the specific energy of Li-ion batteries (LIBs) without changing the underlying materials chemistry. However, the low Li-ion conductivity caused by ultralong Li-ion transport pathway in traditional random microstructured electrode heavily deteriorates the rate performance of ultrathick electrodes. Herein, inspired by the vertical microchannels in natural wood as the highway for water transport, the microstructures of wood are successfully duplicated into ultrathick bulk LiCoO 2 (LCO) cathode via a sol-gel process to achieve the high areal capacity and excellent rate capability. The X-ray-based microtomography demonstrates that the uniform microchannels are built up throughout the whole wood-templated LCO cathode bringing in 1.5 times lower of tortuosity and ≈2 times higher of Li-ion conductivity compared to that of random structured LCO cathode. The fabricated wood-inspired LCO cathode delivers high areal capacity up to 22.7 mAh cm -2 (five times of the existing electrode) and achieves the dynamic stress test at such high areal capacity for the first time. The reported wood-inspired design will open a new avenue to adopt natural hierarchical structures to improve the performance of LIBs., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: We designed a phase i study of concurrent chemoradiotherapy (ccrt) with docetaxel (D) and cisplatin (C), followed by consolidation dc, for unresectable stage iii non-small cell lung cancer (nsclc)., Methods: Patients with histologically proven and unresectable stage iii nsclc were eligible. During ccrt, C was given every 3 weeks (75 mg/m 2 ) and D given weekly. The starting dose of D was 20 mg/m 2 , escalated in cohorts of 3 to define the maximum tolerated dose (mtd). Radiotherapy was prescribed to a dose of 60 Gy in 30 fractions. This was followed by 2 cycles of consolidation dc, which were dose escalated if ccrt was tolerated., Results: Twenty-six patients were enrolled, with 1 excluded following evidence of metastatic disease. Nineteen patients completed both phases of treatment. There were 7 grade 3 events during ccrt (5 esophagitis, 2 nausea), and 8 grade 3 events during consolidation (2 neutropenia, 2 leukopenia, 1 esophagitis, 2 nausea, and 1 pneumonitis). Three patients had grade 4 neutropenia. No patients died due to toxicities. The mtd of concurrent weekly D was 20 mg/m 2 . Consolidation D and C were each dose escalated to 75 mg/m 2 in 8 patients. The median overall survival (os) and progression-free survival (pfs) of all patients were 33.6 months and 17.2 months, respectively, with median follow-up of 26.6 months (range 0.43-110.8)., Conclusions: The use of docetaxel 20 mg/m 2 weekly and cisplatin 75 mg/m 2 every 3 weeks concurrent with thoracic radiotherapy, followed by consolidation docetaxel and cisplatin, both given at 75 mg/m 2 every 3 weeks, appears to be safe in this phase i trial.

Objective: Events occurring during the initial phase of human immunodeficiency virus (HIV) infection are intriguing because of their dramatic impact on the subsequent course of the disease. In particular, the relationship between myeloid-derived suppressor cells (MDSCs) and HIV pathogenesis in primary infection remains unknown and the mechanism of MDSCs in HIV infection are incompletely defined., Methods: The frequency of MDSC expression in patients with primary HIV infection (PHI) and chronic HIV infection was measured, and the association with disease progression was studied. Programmed death-ligand 1 (PD-L1) and galectin-9 (Gal-9) expression on MDSCs was measured and in vitro blocking experiments were performed to study the role of PD-L1 in MDSCs' inhibition., Results: We found increased levels of HLA-DRCD14CD33CD11b granulocytic(G)-MDSCs in PHI individuals compared with normal controls, which correlated with viral loads and was negatively related to CD4 T-cell levels. When cocultured with purified G-MDSCs, both proliferation and interferon-γ secretion by T cell receptor (TCR)-stimulated CD8 T cells from HIV-infected patients were significantly inhibited. We also demonstrated that PD-L1, but not Gal-9, expression on HLA-DRCD14CD33CD11b cells increased during HIV infection. The suppressive activity of G-MDSCs from HIV-infected patients was attenuated by PD-L1 blockade., Conclusions: We found a significant increase in G-MDSCs in PHI patients that was related to disease progression and PD-L1 was used by MDSCs to inhibit CD8 T cells in HIV infection. Our data improve the understanding of HIV pathogenesis in PHI.

Nanostructured metal sulfide-amine hybrid materials have attracted attention because of their unique properties and versatility as precursors for functional inorganic nanomaterials. However, large-scale synthesis of metal sulfide-amine hybrid nanomaterials is limited by hydrothermal and solvothermal preparative reaction conditions; consequently, incorporation of such materials into functional nanomaterials is hindered. An amine molecule-assisted refluxing method was used to synthesize highly uniform zinc sulfide⋅(diethylenetriamine) 0.5 (ZnS⋅(DETA) 0.5 ) hybrid nanosheets and nanobelts in a large scale. The obtained ZnS⋅(DETA) 0.5 hybrid nanomaterials can be used as efficient precursors to fabricate functional ZnS nanomaterials and carbon encapsulated sulfur (S@C) nanocomposite cathodes for Li-S batteries., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Separators, necessary components to isolate cathodes and anodes in Li/Na-ion batteries, are consumed in large amounts per year; thus, their sustainability is a concerning issue for renewable energy storage systems. However, the eco-efficient and environmentally friendly fabrication of separators with a high mechanical strength, excellent thermal stability, and good electrolyte wettability is still challenging. Herein, we reported the fabrication of a new type of separators for Li/Na-ion batteries through the self-assembly of eco-friendly chitin nanofibers derived from prawn shells. We demonstrated that the pore size in the chitin nanofiber membrane (CNM) separator can be tuned by adjusting the amount of pore generation agent (sodium dihydrogen citrate) in the self-assembly process of chitin nanofibers. By optimizing the pore size in CNM separators, the electrochemical performance of the LiFePO 4 /Li half-cell with a CNM separator is comparable to that with a commercialized polypropylene (PP) separator. More attractively, the CNM separator showed a much better performance in the LiFePO 4 /Li cell at 120 °C and Na 3 V 2 (PO 4 ) 3 /Na cell than the PP separator. The proposed fabrication of separators by using natural raw materials will play a significant contribution to the sustainable development of renewable energy storage systems.