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Abstract Carbon‐based fiber materials are widely used in aerospace, military, and electronics owing to their outstanding comprehensive properties. However, the high degree of crystallization and chemical inertness of their surfaces impede the coloring of such materials by traditional dyeing methods, thereby limiting their application in a broader field. Exploring advanced micro/nano‐processing technology for colored carbon‐based fiber materials has become a growing interdisciplinary research area in recent years. Therefore, this review comprehensively discusses the structure‒color‒function relationships of carbon‐based fiber materials. The structure of carbon‐based fiber materials and their properties responsible for challenges in coloring by traditional dyeing methods are discussed. Moreover, the color‐generating mechanisms underlying the display of structural colors by living organisms due to fundamental optical phenomena, including thin/multilayer‐film interference, diffraction grating, scattering, and photonic crystals, are described. Furthermore, recent progress in bio‐inspirated colored carbon‐based fiber materials prepared via advanced micro/nanoscale manufacturing strategies is reviewed. In addition, emerging applications of colored carbon‐based fiber materials in various fields are presented. Finally, the possible challenges and future directions for the design, large‐scale production, and application of colored carbon‐based fiber materials and their composites are discussed, aiming to promote the material design of innovative next‐generation systems and research in the advanced material and related engineering fields.

To investigate the effects of administering fermented milk with live Bifidobacterium lactis Y6 on intestinal health in people with digestive dysfunction, a dietary intervention experiment was conducted. Volunteers with digestive problems were selected to consume 200 mL Y6 fermented milk daily for 4 weeks. Clinical scores were performed before and after the intervention, the Illumina PE300 sequencing platform was used to perform high-throughput sequencing of 16S rDNA PCR product fragments of fecal microorganisms in volunteers, the content of short-chain fatty acids (SCFAs) in feces was determined using gas chromatography. The results showed that drinking Y6 fermented milk had a significant improvement on clinical symptoms caused by digestive dysfunction (P

Aramid fibers (AFs) are widely applied as structural material, cordage, and versatile protection in many harsh environments, including space and deep sea. However, intense ultraviolet (UV)/ irradiation, high/low temperatures, and/or chemical solvent with strong acid/alkali/corrosion feature seriously affect their mechanical properties, thus severely shorten the life cycle of AF-based products. Inspiration by the principle of multiple refractions and partly reflections, an innovative strategy by depositing of laminated Al2O3/TiO2 composite onto the surface of poly(m-phenylene isophthalamide) (PMIA) via atomic layer deposition (ALD) technique was presented. The tenacity of ALD-coated PMIA only decreases by ∼ 8 %, and the yellowness index (YI) only increasing to 129.24 %, far lower than 321.63 % of pristine PMIA fabric under the combination of intense UV irradiation (4260 W/m2) and high temperature (200 °C + ) for 6 h, which equals to continuous strong sunlight exposure for approximately 7.5 years. Meanwhile, ultraviolet protection factor (UPF) value increased to 126.4, which is double that of the pristine PMIA fabric, exhibiting an impressive UV-resistance property. Furthermore, the ALD-coated PMIAs also shows a significant enhancement in both chemical and thermal stabilities. In all, this work not only forge a new route for the functionalization of fibrous materials, but also exhibits great promise for next generation advanced composite material and cutting-edge equipment in harsh environment.

Abstract Background Patients with non‐small‐cell lung cancer (NSCLC) and uncommon EGFR alterations typically have worse treatment outcomes than patients with classically EGFR‐mutated NSCLC. This study aimed to investigate the efficacy and safety of PD‐1 blockade with sintilimab plus anti‐angiogenic treatment with anlotinib in patients with NSCLC harboring uncommon EGFR mutations. Methods Patients with metastatic NSCLC harboring uncommon EGFR mutations after two previous treatments, including a platinum‐based chemotherapy regimen and a targeted treatment (or chemotherapy only for patients harboring EGFR ex20ins), received sintilimab combined with anlotinib. The primary endpoint was objective response rate (ORR). Results At data cutoff (September 27, 2022), median follow‐up was 22.3 months (range, 1.2–37.6). Among 21 enrolled patients, 12 had EGFR ex20ins and nine had other uncommon EGFR mutations such as L861Q, G719A, and G709X. Overall, eight patients (38.1%) achieved an objective response, and 18 (85.7%) achieved disease control. Median (95% CI) progression‐free survival (PFS) was 7.0 (5.4–8.6) months, and median overall survival (OS) was 20.0 (15.6–24.4) months. The 12‐month PFS rate (95% CI) was 22.2% (7.4–42.0), and the 12‐month OS rate was 66.7% (42.5–82.5). Patients harboring EGFR ex20ins had similar ORR and PFS to those with other mutations. Six patients (28.6%) experienced grade 3 treatment‐related adverse events (TRAEs); hand‐foot syndrome was the most common grade 3 TRAE (2 patients; 9.5%). No grade ≥4 TRAEs were observed. Conclusions The combination of sintilimab and anlotinib demonstrated durable efficacy and was generally well tolerated in patients with NSCLC and uncommon EGFR mutations who had received prior standard‐of‐care treatments. (ClinicalTrials.gov identifier: NCT04790409).

BackgroundQL1604 is a humanized immunoglobulin G4 monoclonal antibody against programmed cell death protein 1. This first-in-human, open-label phase I study aimed to investigate the safety and tolerability and to identify the recommended doses of QL1604 for future studies. Pharmacokinetics/pharmacodynamics (PK/PD) and preliminary antitumor activity were also assessed.MethodsPatients with advanced or metastatic solid tumors who failed or had no standard therapies available were recruited. In the dose-escalation phase, patients were treated with QL1604 at 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg intravenously once every 2 weeks (Q2W) in an accelerated titration with a traditional 3 + 3 design, followed by a dose-expansion phase at 3 mg/kg Q2W, 3 mg/kg once every 3 weeks (Q3W), 10 mg/kg Q2W and a fixed dose of 200 mg Q3W. Dose-limiting toxicities (DLTs) were assessed during the first 28 days after the first dose of study drug. Adverse events (AEs) were graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0, and antitumor activity of QL1604 was evaluated by investigators on the basis of Response Evaluation Criteria in Solid Tumors version 1.1.ResultsA total of 35 patients with advanced or metastatic solid tumors were enrolled. DLTs were reported in one patient at the dose level of 3 mg/kg Q2W (grade 3 immune-mediated myositis and myasthenia gravis), and maximum tolerated dose was not reached. The most frequent treatment-related AEs (≥10%) were fatigue (37.1%), anemia (22.9%), increased blood thyroid-stimulating hormone (17.1%), increased aspartate aminotransferase (AST) (17.1%), increased alanine aminotransferase (ALT) (14.3%), decreased white blood cell (WBC) count (11.4%), rash (14.3%), and pruritus (14.3%). AEs leading to discontinuation of QL1604 occurred in three of the 35 patients (8.6%). Partial responses (PRs) occurred in seven patients, resulting in an objective response rate of 20.0% (7/35). Single dose of QL1604 exhibited a dose-dependent increase in the exposure ranging from 0.3 mg/kg to 10 mg/kg. Mean receptor occupancy (RO) for QL1604 at the dose of 3 mg/kg (Q2W and Q3W) and 200 mg (Q3W) was greater than 80% during cycle 1 after one infusion.ConclusionQL1604 monotherapy exhibited favorable safety, PK, and signal of antitumor activity in patients with advanced or metastatic solid tumors, and the results supported further clinical studies of QL1604. On the basis of the safety, PK, and RO data, the recommended dosage for further clinical trials is 3 mg/kg or a fixed dose of 200 mg given every 3 weeks.Clinical Trial Registrationhttps://classic.clinicaltrials.gov/ct2/show/NCT05649761?term=QL1604&draw=2&rank=1, identifier NCT05649761.

Due to its limited intelligence and abilities, machine learning is currently unable to handle various situations thus cannot completely replace humans in real-world applications. Because humans exhibit robustness and adaptability in complex scenarios, it is crucial to introduce humans into the training loop of artificial intelligence (AI), leveraging human intelligence to further advance machine learning algorithms. In this study, a real-time human-guidance-based (Hug)-deep reinforcement learning (DRL) method is developed for policy training in an end-to-end autonomous driving case. With our newly designed mechanism for control transfer between humans and automation, humans are able to intervene and correct the agent’s unreasonable actions in real time when necessary during the model training process. Based on this human-in-the-loop guidance mechanism, an improved actor-critic architecture with modified policy and value networks is developed. The fast convergence of the proposed Hug-DRL allows real-time human guidance actions to be fused into the agent’s training loop, further improving the efficiency and performance of DRL. The developed method is validated by human-in-the-loop experiments with 40 subjects and compared with other state-of-the-art learning approaches. The results suggest that the proposed method can effectively enhance the training efficiency and performance of the DRL algorithm under human guidance without imposing specific requirements on participants’ expertise or experience.

Abstract Previous small-size studies reported BRAF-mutated NSCLC patients have comparable sensitivity to immune checkpoint inhibitors (ICIs). However, how BRAF mutation affects the tumor immune microenvironment (TIME) is unknown. We performed Nanostring-panel RNA sequencing to evaluate TIME in 57 BRAF mutated and wild-type (WT) NSCLC specimens (cohort A). The efficacy of ICI monotherapy or combined therapies was determined in 417 patients with WT and BRAF mutated NSCLC (cohort B). We found that BRAF-mutant tumors had similar ratios of CD8+ T cells to Tregs, the balance of cytotoxicity gene expression signatures and immune suppressive features, and similar ICI-response-related biomarkers to WT NSCLC. A similar TIME pattern was observed between the BRAF V600E and Non-V600E subgroups of NSCLC. The further retrospective study confirmed that treatment with ICI monotherapy or combined therapies resulted in similar overall survival (OS) (HR: 0.85; 95% CI, 0.56 to 1.30; p = 0.47) and progress-free survival (PFS) (HR: 1.02; 95% CI, 0.72 to 1.44; p = 0.91) of patients with WT (n = 358) and BRAF mutant (n = 59) NSCLC. Similarly, both patients with BRAF V600E or Non-V600E NSCLC had similar responses to immunotherapy. Our findings support that BRAF mutation did not modulate TIME in NSCLC and therapeutic responses to ICIs. Patients with NSCLC harboring BRAF mutation should not be denied treatment with ICIs.

In order to understand the current situation and measures of physical training of volleyball team in higher vocational colleges, this paper takes the current situation of physical training of volleyball team in Higher Vocational Colleges as the object, starting with the physical training of volleyball team in Higher Vocational Colleges as the starting point, using the methods of literature review, questionnaire survey, expert interview and mathematical statistics, briefly discusses the concept of physical training of volleyball team in Higher Vocational Colleges at this stage, and analyzes the current stage of vocational colleges This paper analyzes the performance of insufficient physical training of college volleyball team, and introduces the new concept of physical training to analyze the optimization measures of physical training of volleyball team in higher vocational colleges. It is concluded that the basic situation of volleyball players in higher vocational colleges is not different, which has no great impact on physical training, but the physical training lacks certain scientificity, and the training mode is relatively single, and the training plan is not targeted. Through scientific physical training, we can improve the competitive ability of volleyball players in higher vocational colleges. Therefore, physical fitness is an important component of the competitive ability of volleyball players in higher vocational colleges, and good physical quality is the key for volleyball players in Higher Vocational Colleges to have high-level technology and obtain good sports results.

An ultraviolet (UV)-protective cotton fabric has been developed by combining tannic acid and copper ions (TA-Cu) on cotton fabrics. The structure and properties of TA-Cu and cotton fabrics finished with TA-Cu were characterized by Fourier-transform infrared spectroscopy, ultraviolet-visible spectroscopy, scanning electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The UV resistance and laundering durability of modified cotton fabrics were measured. The cotton fabric finished with tannic acid showed a maximum UV-protection factor value of 44.5, which was further improved by chelation with copper ions. The cotton fabric finished by the TA-Cu exhibits a UV-protection factor value of up to 172.1 and a UV transmittance of less than 1.5% when the concentration of tannic acid and copper ions was 0.1 mmol/L. The as-prepared cotton fabrics retained their UV resistance after laundering. This study proposes an eco-friendly anti-UV treatment for cotton fabrics and a novel application for tannic acid and copper ions to imbue fabrics with UV protection.

BackgroundThe circulating predictive factors for the outcomes of advanced non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs) remain elusive. We aimed to assess the predictive value of circulating cytokines for outcomes.MethodsSerum samples of 102 advanced-stage NSCLC patients who underwent immunotherapy were collected at baseline. The relative levels of 37 cytokines were detected. PD-L1 expression was also analyzed.ResultsHigher serum CXCL12 levels (top 33%) were a poor predictive biomarker for durable clinical benefit (DCB) (23.5% vs. 72.1%, p

Abstract Background Determining the tissue of origin (TOO) is essential for managing cancer of unknown primary (CUP). In this study, we evaluated the concordance between genome profiling and DNA methylation analysis in determining TOO for lung-specific CUP and assessed their performance by comparing the clinical responses and survival outcomes of patients predicted with multiple primary or with metastatic cancer. Methods We started by retrospectively screening for CUP patients who presented with both intra- and extrathoracic tumors. Tumor samples from included patients were analyzed with targeted sequencing with a 520-gene panel and targeted bisulfite sequencing. TOO inferences were made in parallel via an algorithm using genome profiles and time interval between tumors and via machine learning-based classification of DNA methylation profiles. Results Four hundred patients were screened retrospectively. Excluding patients definitively diagnosed with conventional diagnostic work-up or without available samples, 16 CUP patients were included. Both molecular approaches alone enabled inference of clonality for all analyzed patients. Genome profile enabled TOO inference for 43.8% (7/16) patients, and the percentage rose to 68.8% (11/16) after considering inter-tumor time lag. On the other hand, DNA methylation analysis was conclusive for TOO prediction for 100% (14/14) patients with available samples. The two approaches gave 100% (9/9) concordant inferences regarding clonality and TOO identity. Moreover, patients predicted with metastatic disease showed significantly shorter overall survival than those with multiple primary tumors. Conclusions Genome and DNA methylation profiling have shown promise as individual analysis for TOO identification. This study demonstrated the feasibility of incorporating the two methods and proposes an integrative scheme to facilitate diagnosing and treating lung-specific CUPs.

Abstract Accumulating evidence indicates that inflammation and nutrition status are associated with clinical outcomes in patients with various malignancies. This study aimed to evaluate the prognostic significance of the pretreatment platelet to albumin ratio (PAR) in esophageal squamous cell carcinoma (ESCC) patients undergoing definitive radiotherapy. A total of 470 patients who underwent definitive radiotherapy with or without chemotherapy were enrolled. The optimal cut-off values of PAR and other indicators were determined by the X-tile. The Kaplan–Meier method, multivariate analyses Cox regression were conducted to identify the association between those indicators and the survival outcomes. The median follow-up time was 23.5 months. The optimal cut-off value of PAR was 5.7 × 109 and patients were stratified as the low PAR group and the high PAR group. In the univariate analysis, a low overall survival rate was significantly associated with T stage (P = 0.005), TNM stage (P

Abstract Bone morphogenetic protein 1 (BMP1) belongs to the astacin/BMP1/tolloid-like family of zinc metalloproteinases, which play a fundamental role in the development and formation of extracellular matrix (ECM). BMP1 mediates the cleavage of carboxyl terminal (C-term) propeptides from procollagens, a crucial step in fibrillar collagen fiber formation. Blocking BMP1 by small molecule or antibody inhibitors has been linked to anti-fibrotic activity in the preclinical models of skin, kidney and liver fibrosis. Therefore, we reason that BMP1 may be important for the pathogenesis of lung fibrosis and BMP1 could be a potential therapeutic target for progressive fibrotic disease such as idiopathic pulmonary fibrosis (IPF). Here, we observed the increased expression of BMP1 in both human IPF lungs and mouse fibrotic lungs induced by bleomycin. Furthermore, we developed an inducible Bmp1 conditional knockout (cKO) mouse strain. We found that Bmp1 deletion does not protect mice from lung fibrosis triggered by bleomycin. Moreover, we found no significant impact of BMP1 deficiency upon C-term propeptide of type I procollagen (CICP) production in the fibrotic mouse lungs. Based on these results, we propose that BMP1 is not required for lung fibrosis in mice and BMP1 may not be considered a candidate therapeutic target for IPF.

Abstract Background Brain metastasis is a common and lethal complication of non-small cell lung cancer (NSCLC). It is mostly diagnosed only after symptoms develop, at which point very few treatment options are available. Therefore, patients who have an increased risk of developing brain metastasis need to be identified early. Our study aimed to identify genomic and epigenomic biomarkers for predicting brain metastasis risk in NSCLC patients. Methods Paired primary lung tumor tissues and either brain metastatic tissues or cerebrospinal fluid (CSF) samples were collected from 29 patients with treatment-naïve advanced NSCLC with central nervous system (CNS) metastases. A control group comprising 31 patients with advanced NSCLC who died without ever developing CNS metastasis was also included. Somatic mutations and DNA methylation levels were examined through capture-based targeted sequencing with a 520-gene panel and targeted bisulfite sequencing with an 80,672 CpG panel. Results Compared to primary lung lesions, brain metastatic tissues harbored numerous unique copy number variations. The tumor mutational burden was comparable between brain metastatic tissue (P = 0.168)/CSF (P = 0.445) and their paired primary lung tumor samples. Kelch-like ECH-associated protein (KEAP1) mutations were detected in primary lung tumor and brain metastatic tissue samples of patients with brain metastasis. KEAP1 mutation rate was significantly higher in patients with brain metastasis than those without (P = 0.031). DNA methylation analysis revealed 15 differentially methylated blocks between primary lung tumors of patients with and without CNS metastasis. A brain metastasis risk prediction model based on these 15 differentially methylated blocks had an area under the curve of 0.94, with 87.1% sensitivity and 82.8% specificity. Conclusions Our analyses revealed 15 differentially methylated blocks in primary lung tumor tissues, which can differentiate patients with and without CNS metastasis. These differentially methylated blocks may serve as predictive biomarkers for the risk of developing CNS metastasis in NSCLC. Additional larger studies are needed to validate the predictive value of these markers.

Herein, a comprehensive examination of the effect of concentration on graphene oxide (GO) photoluminescence (PL) is presented. It is found that GO exhibits a concentration‐induced redshift and white light PL for GO aqueous dispersions, and displays visible–NIR PL for a 3D GO foam (3DGOF) corresponding to the high‐concentration‐limit of GO. It is deduced that the effect of the coupling between the GO sheets gives rise to the observed redshift, and hopping and tunneling effects result in the saturation of the PL redshift and then the PL quenching. Due to the intense interactions and coupling of the GO sheets, the modification of the GO surface state increases the energy of the π* state and/or makes the high‐energy level appear and therefore gives rise to the blue light component. Consequently, high concentrations of GO aqueous dispersion lead to the appearance of combined white light. For 3DGOF, electron–hole radiation recombination in laser‐induced plasma and GO bandgap may be responsible for the observed visible–NIR PL. Based on its tunable PL in the visible–NIR region of the spectrum and the induced white light PL, GO has huge potential for applications in graphene‐based optoelectronics and biomedicine.

BackgroundSmall-cell lung cancer (SCLC) is the most lethal cancer. With the development of chemotherapy and radiotherapy, brain metastasis (BM) emerged as one most predominant treatment failure. However, the factors affecting BM have not been identified completely. The purpose of this study was to investigate the risk factors involved in the development of BM in patients with limited-stage small-cell lung cancer (LS-SCLC) following definitive thoracic radiotherapy (TRT) and to provide a reference for the planning of a clinical treatment strategy.MethodsThe clinical data of patients with LS-SCLC treated with neoadjuvant chemotherapy (NAC) followed by TRT were collected and retrospectively reviewed. The factors affecting BM, BM-free survival (BMFS) and overall survival (OS) rates were analyzed statistically.ResultsA total of 152 patients with LS-SCLC fulfilled the inclusion criteria were reviewed. Following TRT, 31 (20.4%) patients achieved CR, 90 (59.2%) patients reached PR, 31 (20.4%) patients maintained SD, and no patients developed PD. The OS at 1, 3, and 5 years was 80.6, 34.2, and 19.4%, respectively. Multivariate analyses indicated that the greatest dimension of primary tumor (Dmax-T) and short-term response to TRT were risk factors affecting BM. The clinical N stage (cN), greatest dimension of metastatic nodes (Dmax-N), short-term response to TRT, and adjuvant chemotherapy (AC) were identified as independent factors correlated with OS.ConclusionsPoor short-term response to TRT and huger Dmax-T were risk factors for BM. AC following TRT improved patient survival, but not decreased BM. However, due to the limitations associated with the retrospective design of the present study, further prospective clinical trials are required to confirm these conclusions.

Photoacoustic microscopy (PAM) and optical coherence tomography (OCT) are sensitive to optical absorption and scattering characteristics, respectively. As such, the integration of these two modalities in order to combine important complementary information has garnered much attention. Due to the relatively low axial resolution of PAM, PAM and OCT dual modality systems generally have a large resolution gap, especially for reflection mode systems. In this study, based on a wide-band transparent pure-optical ultrasonic detector, we developed a dual modality system (PAM-OCT system) in which PAM has a similar spatial resolution (i.e. several micrometers in both the lateral and axial directions) to OCT. In addition, due to the optical transparency advantage, the integrated system works in reflection mode, which is ideal for in vivo biomedical imaging. We successfully imaged the skin of a mouse hindlimb, which cannot be done by a transmission mode dual modality system. Our work demonstrates this dual modality system has potential in biomedical studies with complementary imaging contrasts.

Background/Aims: Cyclin-dependent kinase 6 (CDK6) regulates inflammatory response and cell differentiation. This study sought to determine whether CDK6 and miR-320c co-regulate chondrogenesis and inflammation. Methods: Utilizing quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC), CDK6 and miR-320c expression were assessed in a micromass culture of human bone mesenchymal stem cells that underwent chondrogenesis in vitro as well as in chondrocytes from E16.5 mouse forelimbs. Normal chondrocytes were transfected with miR-320c mimic, miR-320c inhibitor, or CDK6-siRNA. Luciferase reporter assay results confirmed that miR-320c directly targets CDK6 by interacting with the 3′-untranslated region (3′-UTR) of its mRNA. qRT-PCR, Western blotting, and Cell Counting Kit-8 were subsequently used to evaluate the effects of miR-320c overexpression and CDK6 inhibition on inflammatory factor expression, as well as to investigate the effects of NF-kB and MAPK signaling pathway activation on IL-1β-induced chondrocyte inflammation. Results: Our results show that miR-320c expression increased during the middle stage and decreased during the late stage of hBMSC chondrogenic differentiation. In contrast, CDK6 expression decreased during the middle stage and increased during the late stage of hBMSC chondrogenic differentiation. Moreover, CDK6 expression increased in severe OA cartilage and in hypertrophic chondrocytes of mouse forelimbs at E16.5. Results of the luciferase reporter assay showed that miR-320c modulated CDK6 expression by binding to the 3′-UTR of its mRNA. miR-320c overexpression and CDK6 inhibition repressed IL-1β-induced expression of inflammatory factors and regulated the NF-kB signaling pathway. Conclusion: CDK6 and miR-320c co-regulate hBMSC chondrogenesis and IL-1β-induced chondrocyte inflammation through the NF-kB signaling pathway, suggesting that miR-320c and CDK6 inhibitors can be used to repress catabolism in human chondrocytes.

Abstract Background WNT5A is known to be involved in the pathogenesis of osteoarthritis. This study investigated the molecular mechanism of exosomal miR-92a-3p and WNT5A in chondrogenesis and cartilage degeneration. Methods Exosomal miR-92a-3p expression was assessed in vitro in a human mesenchymal stem cell (MSC) model of chondrogenesis and in normal and OA primary human chondrocytes (PHCs). MSCs and PHCs were treated with exosomes derived from MSC-miR-92a-3p (MSC-miR-92a-3p-Exos) or its antisense inhibitor (MSC-anti-miR-92a-3p-Exos), respectively. Small interfering RNAs (siRNAs) and luciferase reporter assay were used to reveal the molecular role of exosomal miR-92a-3p and WNT5A in chondrogenesis. The protective effect of exosomes in vivo was measured using Safranin-O and Fast Green staining and immunohistochemical staining. Results Exosomal miR-92a-3p expression was elevated in the MSC chondrogenic exosome, while it was significantly reduced in the OA chondrocyte-secreted exosome compared with normal cartilage. Treatment with MSC-miR-92a-3p-Exos promoted cartilage proliferation and matrix genes expression in MSCs and PHCs, respectively. In contrast, treatment with MSC-anti-miR-92a-3p-Exos repressed chondrogenic differentiation and reduced cartilage matrix synthesis by enhancing the expression of WNT5A. Luciferase reporter assay demonstrated that miR-92a-3p suppressed the activity of a reporter construct containing the 3’-UTR and inhibited WNT5A expression in both MSCs and PHCs. MSC-miR-92a-3p-Exos inhibit cartilage degradation in the OA mice model. Conclusions Our results suggest that exosomal miR-92a-3p regulates cartilage development and homeostasis by directly targeting WNT5A. This indicates that exosomal miR-92a-3p may act as a Wnt inhibitor and exhibits potential as a disease-modifying osteoarthritis drug.

Abstract Background Fundus fluorescein angiography (FFA) imaging is a standard diagnostic tool for many retinal diseases such as age-related macular degeneration and diabetic retinopathy. High-resolution FFA images facilitate the detection of small lesions such as microaneurysms, and other landmark changes, in the early stages; this can help an ophthalmologist improve a patient’s cure rate. However, only low-resolution images are available in most clinical cases. Super-resolution (SR), which is a method to improve the resolution of an image, has been successfully employed for natural and remote sensing images. To the best of our knowledge, no one has applied SR techniques to FFA imaging so far. Methods In this work, we propose a SR method-based pipeline for FFA imaging. The aim of this pipeline is to enhance the image quality of FFA by using SR techniques. Several SR frameworks including neighborhood embedding, sparsity-based, locally-linear regression and deep learning-based approaches are investigated. Based on a clinical FFA dataset collected from Second Affiliated Hospital to Xuzhou Medical University, each SR method is implemented and evaluated for the pipeline to improve the resolution of FFA images. Results and conclusion As shown in our results, most SR algorithms have a positive impact on the enhancement of FFA images. Super-resolution forests (SRF), a random forest-based SR method has displayed remarkable high effectiveness and outperformed other methods. Hence, SRF should be one potential way to benefit ophthalmologists by obtaining high-resolution FFA images in a clinical setting.

Background/Aims: Long noncoding RNAs (lncRNAs) play important roles in stem cell differentiation. However, their role in osteogenesis of human adipose-derived stem cells (ASCs), a promising cell source for bone regeneration, remains unknown. Here, we investigated the expression profile and potential roles of lncRNAs in osteogenic differentiation of human ASCs. Methods: Human ASCs were induced to differentiate into osteoblasts in vitro, and the expression profiles of lncRNAs and mRNAs in undifferentiated and osteogenic differentiated ASCs were obtained by microarray. Bioinformatics analyses including subgroup analysis, gene ontology analysis, pathway analysis and co-expression network analysis were performed. The function of lncRNA H19 was determined by in vitro knockdown and overexpression. Quantitative reverse transcription polymerase chain reaction was utilized to examine the expression of selected genes. Results: We identified 1,460 upregulated and 1,112 downregulated lncRNAs in osteogenic differentiated human ASCs as compared with those of undifferentiated cells (Fold change ≥ 2.0, P < 0.05). Among these, 94 antisense lncRNAs, 85 enhancer-like lncRNAs and 160 lincRNAs were further recognized. We used 12 lncRNAs and 157 mRNAs to comprise a coding-non-coding gene expression network. Additionally, silencing of H19 caused a significantly increase in expression of osteogenesis-related genes, including ALPL and RUNX2, while a decrease was observed after H19 overexpression. Conclusion: This study revealed for the first time the global expression profile of lncRNAs involved in osteogenic differentiation of human ASCs and provided a foundation for future investigations of lncRNA regulation of human ASC osteogenesis.

Colony-stimulating factor 1 (CSF1) and interleukin 34 (IL34) signal via the CSF1 receptor to regulate macrophage differentiation. Studies in IL34- or CSF1-deficient mice have revealed that IL34 function is limited to the central nervous system and skin during development. However, the roles of IL34 and CSF1 at homeostasis or in the context of inflammatory diseases or cancer in wild-type mice have not been clarified in vivo. By neutralizing CSF1 and/or IL34 in adult mice, we identified that they play important roles in macrophage differentiation, specifically in steady-state microglia, Langerhans cells, and kidney macrophages. In several inflammatory models, neutralization of both CSF1 and IL34 contributed to maximal disease protection. However, in a myeloid cell-rich tumor model, CSF1 but not IL34 was required for tumor-associated macrophage accumulation and immune homeostasis. Analysis of human inflammatory conditions reveals IL34 upregulation that may account for the protection requirement of IL34 blockade. Furthermore, evaluation of IL34 and CSF1 blockade treatment during Listeria infection reveals no substantial safety concerns. Thus, IL34 and CSF1 play non-redundant roles in macrophage differentiation, and therapeutic intervention targeting IL34 and/or CSF1 may provide an effective treatment in macrophage-driven immune-pathologies.

A superwicking Ti-6Al-4V alloy material with a hierarchical capillary surface structure was fabricated using femtosecond laser. The basic capillary surface structure is an array of micropillars/microholes. For enhancing its capillary action, the surface of the micropillars/microholes is additionally structured by regular fine microgrooves using a technique of laser-induced periodic surface structures (LIPSS), providing an extremely strong capillary action in a temperature range between 23 °C and 80 °C. Due to strong capillary action, a water drop quickly spreads in the wicking surface structure and forms a thin film over a large surface area, resulting in fast evaporation. The maximum water flow velocity after the acceleration stage is found to be 225–250 mm/s. In contrast to other metallic materials with surface capillarity produced by laser processing, the wicking performance of which quickly degrades with time, the wicking functionality of the material created here is long-lasting. Strong and long-lasting wicking properties make the created material suitable for a large variety of practical applications based on liquid-vapor phase change. Potential significant energy savings in air-conditioning and cooling data centers due to application of the material created here can contribute to mitigation of global warming.

A chatter vibration in milling process results in poor surface finish and machining efficiency. To avoid the chatter vibration, the stability lobe diagram (SLD) which is the function of tool point frequency response functions (FRFs) is adopted to predict the chatter-free machining parameters. However, the tool point FRF varies with the changes of machining positions and feed directions within machine tool work volume. Considering this situation, this paper presents a method to predict the position and feed direction-dependent tool point FRF. First, modal parameters of the tool point FRFs obtained at some typical positions and feed directions are identified by the modal theory and matrix transformation method. With the sample information, a back propagation (BP) neural network whose inputs are the position coordinates and feed angle and outputs are the modal parameters can be trained with the aid of the particle swarm optimization (PSO) algorithm. Then, modal parameters corresponding to any position and feed direction can be predicted by the trained BP neural network and used to reorganize the tool point FRFs with the modal fitting technique. A case study was performed on a real vertical machining center to demonstrate the accurate prediction of position and feed direction-dependent tool point FRFs. Furthermore, the position and feed direction-dependent milling stability was researched and origin-symmetric distributions of the limiting axial cutting depths at each machining position were observed.

Capillary flow of water in an array of open nanotextured microgrooves fabricated by femtosecond laser processing of silicon is studied as a function of temperature using high-speed video recording. In a temperature range of 23–80 °C, the produced wicking material provides extremely fast liquid flow with a maximum velocity of 37 cm/s in the initial spreading stage prior to visco-inertial regime. The capillary performance of the material enhances with increasing temperature in the inertial, visco-inertial, and partially in Washburn flow regimes. The classic universal Washburn’s regime is observed at all studied temperatures, giving the evidence of its universality at high temperatures as well. The obtained results are of great significance for creating capillary materials for applications in cooling of electronics, energy harvesting, enhancing the critical heat flux of industrial boilers, and Maisotsenko cycle technologies.

Recently, the immune checkpoint inhibitors which target programmed death-1 (PD-1)/PD-1 ligand (PD-L1) have made a breakthrough in the treatment of advanced non-small cell lung cancer. Researches on immune checkpoint inhibitors have been rapidly implemented in various types of lung cancer, such as small cell lung cancer and locally advanced non-small cell lung cancer. These inhibitors have been applied in combination with other treatment strategies, including chemotherapy, targeting therapy and radiotherapy. However, there are still many problems to be solved, such as searching for ideal biomarkers, exploring different combination treatment models, and identifying the potential mechanisms of primary or secondary drug resistance. Along with these problems to be successfully solved, the immune checkpoint inhibitors will have broader applications in lung cancer therapy.

Background and objective Gemcitabine-platinum-combined with chemotherapy is the most common treatment for advanced non-small cell lung cancer (NSCLC). Gemcitabine is administered once a week in a general three-week schedule. In the present study, gemcitabine is administered on d1 and d5 to improve compliance, and the efficacy and safety of the improved regimen is evaluated in untreated patients with advanced NSCLC. Methods A total of 83 patients were enrolled between October 2007 and October 2009. In each cycle, gemcitabine was administered at a dose of 1,000 mg/m2-1,250 mg/m2 via a 30 min intravenous infusion on d1 and d5 followed by cisplatin at a dose of 75 mg/m2 or carboplatin (AUC=5) on d1 every three weeks. At least two cycles of chemotherapy were completed in each case, and clinical response and toxicity of the regimen were observed. Results The objective response rate was 37.3%. The median progression free survival and overall survival time were 6.1 months and 15.0 months, respectively. The one-year and two-year survival rates were 57.8% and 16.2%, respectively. Myelosuppression and gastrointestinal responses were the main toxicities. The incidence of grade 3/4 of leucopenia, hypohemia, and thrombocytopenia were 26.5%, 10.8% and 7.2%, respectively. A total of 27.5% of the patients in the cisplatin group had grade 3/4 gastrointestinal responses. Treatment related deaths were not observed in this study. Conclusion The regimen is active and well-tolerated in untreated patients with advanced NSCLC. Further randomized controlled studies are necessary.

A ternary copolymer of 2-acrylamide-2-methyl propane sulfonic acid (AMPS), acrylamide (AM), and allyl alcohol polyoxyethylene ether (APEG) with a side chain polyoxyethylene ether (C2H4O)n SJ-1 were designed and synthesized in this work. Good temperature resistance and salt tolerance of “–SO3-” of AMPS, strong absorption ability of “amino-group” of AM, and good hydrability of side chain polyoxyethylene ether (C2H4O)n of APEG provide SJ-1 excellent properties as a fluid loss additive. The chemical structure of ternary copolymer was characterized by Fourier transform infrared (FTIR) spectroscopy. The molecular weight and its distribution were determined by gel permeation chromatography (GPC). The API fluid loss of drilling fluid decreased gradually with the increasing concentration of NaCl and CaCl2 in the mud system. SJ-1 was applied well in the drilling fluid even at a high temperature of 220°C. Results of zeta potential of modified drilling fluid showed the dispersion stability of drilling fluid system. Scanning electron microscopy (SEM) analysis showed the microstructure of the surface of the filter cake obtained from the drilling fluid modified by SJ-1.

To investigate the impact of clinical target volume (CTV) shape and size on CTV to planning target volume (PTV) margin expansion.Using numerical integration methods, margins accounting for random errors and systematic errors were calculated for CTVs of different shapes and sizes. We use k(r-95) and k(s-95) to represent the coefficients, for random errors and systematic errors, respectively, that ensure that every point of the CTV receives ≥95% of the prescribed dose.The part of the margin accounting for random errors depends on CTV shape and size; generally, a convex part of a CTV would have a larger margin than a concave part. However, the part of the margin accounting for systematic errors is independent of CTV shape and size.CTV shape and size should be considered when generating a PTV. For a complex CTV, the margins of the various parts of the CTV are different and related to local forms.

Oil-based drilling fluid is used more and more in the field of oil and gas exploration. However, because of unrecyclable treating agent and hard treatment conditions, the traditional treating technologies of waste oil-based drilling fluid have some defects, such as waste of resource, bulky equipment, complex treatment processes, and low oil recovery rate. In this work, switchable deoiling agent (SDA), as a novel surfactant for treatment of waste oil-based drilling fluid, was synthesized by amine, formic acid, and formaldehyde solution. With this agent, the waste oil-based drilling fluid can be treated without complex process and expensive equipment. Furthermore, the agent used in the treatment can be recycled, which reduces waste of resource and energy. The switch performance, deoiling performance, structural characterization, and mechanisms of action are studied. The experimental results show that the oil content of the recycled oil is higher than 96% and more than 93% oil in waste oil-based drilling fluid can be recycled. The oil content of the solid residues of deoiling is less than 3%.