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Purpose: Standard treatment for patients with unresectable locally advanced or metastatic soft-tissue sarcoma (LA/M STS) is chemotherapy based on anthracyclines, but patient tolerance of chemotherapy is limited. The present trial (NCT03792542) investigated the use of anlotinib as first-line treatment for patients with advanced STS, in particular liposarcoma., Patients and Methods: Eligible patients were previously untreated, pathologically confirmed, unresectable LA/M STS cases. Anlotinib was given orally at a dose of 12 mg once daily from days 1 to 14 every 3 weeks until disease progression or intolerable adverse events (AE) occurred. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate, and disease control rate (DCR). The safety profile was also evaluated., Results: Forty patients were enrolled from April 2019 to June 2022 and are included in the intention-to-treat analysis. The median PFS was 6.83 months [95% confidence interval (CI), 4.17-8.71] and the median OS 27.40 months (95% CI, 16.43-not evaluable); 1 patient reached partial response and 26 attained stable disease, with a DCR of 67.5% (27/40). Median PFS and OS times for liposarcoma patients were 8.71 and 16.23 months, respectively. Ten (25.0%) patients had treatment-related AEs ≥ grade 3, with in particular a higher incidence of hypertension (15.0%) and proteinuria (7.5%)., Conclusions: The findings suggest a potential benefit in using front-line anlotinib to treat patients with STS, who are not eligible for cytotoxic chemotherapy. Of note, the clinical outcomes for the liposarcoma subgroup of patients were encouraging. See related commentary by Napolitano et al., p. 4257., (©2024 The Authors; Published by the American Association for Cancer Research.)

Although copper-catalyzed amination of activated C(sp 3 )-H bonds through radical relay has been developed, amination of unactivated C(sp 3 )-H bonds is rare. Herein, copper-catalyzed intramolecular amination of remote unactivated C(sp 3 )-H bonds is reported. The reaction is conducted in a mild and effective manner with moderate to good yields, demonstrating broad tolerance toward various functional groups and exhibiting complete regio- and chemoselectivities. This innovation supplies novel synthetic pathways for the construction of saturated nitrogenated heterocycles.

The application of supermolecular naonostructures in the photocatalytic carbon dioxide reduction reaction (CO 2 RR) has attracted increasing attentions. However, it still faces significant challenges, such as low selectivity for multi-electron products and poor stability. Here, the cuprous oxide (Cu 2 O)-modified zinc tetraphenylporphyrin ultrathin nanosheets (ZnTPP NSs) are successfully constructed through the aqueous chemical reaction. Comprehensive characterizations confirm the formation of type-II heterojunction between Cu 2 O and ZnTPP in Cu 2 O@ZnTPP, and the electron transfer from Cu 2 O to ZnTPP through the Zn-O-Cu bond under the static contact. Under the visible-light irradiation (λ > 420 nm), the optimized Cu 2 O@ZnTPP sample as catalyst for photocatalytic CO 2 RR exhibits the methane (CH 4 ) evolution rate of 120.9 μmol/g/h, which is ∼ 4 and ∼ 10 times those of individual ZnTPP NSs (28.0 μmol/g/h) and Cu 2 O (12.8 μmol/g/h), respectively. Meanwhile, the CH 4 selectivity of ∼ 98.7 % and excellent stability can be achieved. Further experiments reveal that Cu 2 O@ZnTPP has higher photocatalytic conversion efficiency than Cu 2 O and ZnTPP NSs, and the photoinduced electron transfer from ZnTPP to Cu 2 O can be identified via the path of ZnTPP→ (ZnTPP•ZnTPP)*→ ZnTPP - → Zn-O-Cu → Cu 2 O. Consequently, Cu 2 O@ZnTPP exhibits a shorter electron-hole separation lifetime (3.3 vs. 9.3 ps) and a longer recombination lifetime (23.1 vs. 13.4 ps) than individual ZnTPP NSs. This work provides a strategy to construct the organic nanostructures for photocatalytic CO 2 RR to multi-electron products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In ORIENT-15 study, sintilimab plus chemotherapy demonstrated significant improvement on overall survival (OS) versus placebo plus chemotherapy in first-line treatment of advanced esophageal squamous cell carcinoma (ESCC). Here, we report effect of sintilimab plus chemotherapy on health-related quality of life (HRQoL) in patients with advanced ESCC., Methods: From December 14, 2018 to August 28, 2022, HRQoL was evaluated in all randomized patients using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30), EORTC Quality of Life Questionnaire Oesophageal Cancer Module 18 items (QLQ-OES18), and visual analogue scale (VAS) of the EuroQol five-dimensional five-level questionnaire (EQ-5D-5L). Mean scores of each scale were described by treatment group through week 60. Least-squares mean (LSM) score change from baseline through week 24 were analyzed using the mixed-model repeated-measures method. Time to the first onset of deterioration (TTD) and OS for each scale were estimated. Clinical Trials Registration: NCT03748134., Findings: As of August 28, 2022, 689 of 690 enrolled patients were assessed for HRQoL analysis (sintilimab group: 340, placebo group: 349). Median follow-up was 32.2 months. Differences in LSM favored sintilimab over placebo for QLQ-C30 social functioning (LSM difference: 3.06, 95% CI: 0.55 to 5.57; P = 0.0170), pain (-2.24, 95% CI: -4.30 to -0.17; P = 0.0337), fatigue (-2.24, 95% CI: -4.46 to -0.02; P = 0.0479), constipation (-3.27, 95% CI -5.49 to -1.05; P = 0.0039), QLQ-OES18 pain (-1.77, 95% CI -3.11 to -0.43; P = 0.0097), trouble swallowing saliva (-2.09, 95% CI: -3.77 to -0.42; P = 0.0146), and choked when swallowing (-3.23, 95% CI: -5.60 to -0.86; P = 0.0076). TTD favored sintilimab over placebo for QLQ-OES18 dysphagia (Hazard ratio [HR]: 0.76, 95% CI: 0.61-0.94, P = 0.0104), and trouble swallowing saliva (HR: 0.48, 95% CI: 0.35-0.67, P < 0.0001). Improved OS were observed in patients with better performance in several functioning and symptom scales of QLQ-C30 and QLQ-QES18., Interpretation: The statistically significant differences of several HRQoL scales and improvements in delayed deterioration observed in our study further support the use of sintilimab plus chemotherapy as first-line treatment for advanced ESCC., Funding: This study was funded by Innovent Biologics and was co-funded by Eli Lilly., Competing Interests: All authors reports receiving support from Innovent Biologics and Eli Lilly for the submitted work. LS reports receiving research funding from Innovent Biologics, Beijing Xiantong Biomedical Technology, Qilu Pharmaceutical, ZaiLab Pharmaceutical, Beihai Kangcheng (Beijing) Medical Technology, and Jacobio Pharmaceuticals; consultant fees from MSD, Merck, Mingji Biopharmaceutical, Haichuang Pharmaceutical, Herbour Biomed, and BI; honoraria from Hutchison Whampoa, Hengrui, ZaiLab, and CSTONE pharmaceutical; and serving as a consultant for Rongchang Pharmaceutical, ZaiLab, CSTONE Pharmaceutical, and BMS., (© 2024 The Author(s).)

Sheep horns are composed of bone and sheaths, and the BMPR1A gene is required for cartilage and osteogenic differentiation. Therefore, the BMPR1A gene may have a function related to the sheep horn, but its relationship with the sheep horn remains unclear. In this study, we first utilized RNA sequencing (RNA-seq) data to investigate the expression of the BMPR1A gene in different tissues and breeds of sheep. Second, whole-genome sequencing (WGS) data were used to explore the functional sites of the BMPR1A gene. Lastly, the allele-specific expression of the BMPR1A gene was explored. Our results indicate that BMPR1A gene expression is significantly higher in the normal horn groups than in the scurred groups. Importantly, this trend is consistent across several sheep breeds. Therefore, this finding suggests that the BMPR1A gene may be related to horn type. A total of 43 Single-Nucleotide Polymorphisms (SNPs) (F-statistics > 0.15) and 10 allele-specific expressions (ASEs) exhibited difference between the large and small horn populations. It is probable that these sites significantly impact the size of sheep horns. Compared to other polled species, we discovered ten amino acid sites that could influence horn presence. By combining RNA-seq and WGS functional loci results, we identified a functional site at position 40574836 on chromosome 25 that is both an SNP and exhibits allele-specific expression. In conclusion, we demonstrated that the BMPR1A gene is associated with horn type and identified some important functional sites which can be used as molecular markers in the breeding of sheep horns.

An efficient copper-catalyzed selective fluoromethylthiolation of an inert δ-C(sp 3 )-H bond in sulfonamides was reported. In the presence of a copper catalyst and PhSO 2 SR f , the radical generated through 1,5-hydrogen atom transfer (HAT) was sufficiently trapped by PhSO 2 SR f , instead of copper, which was prevalent in metal-catalyzed radical-relay processes, incorporating a fluoromethylthio group into molecules. The general substrate scope and mild conditions endowed the method with wide potential applications in pharmaceuticals and agrochemicals.

Background: Rhinitis is a complex condition characterized by various subtypes, including allergic rhinitis (AR), which involves inflammatory reactions. The objective of this research was to identify crucial genes associated with inflammatory response that are relevant for the treatment and diagnosis of AR., Methods: We acquired the AR-related expression datasets (GSE75011 and GSE50223) from the Gene Expression Omnibus (GEO) database. In GSE75011, we compared the gene expression profiles between the HC and AR groups and identified differentially expressed genes (DEGs). By intersecting these DEGs with inflammatory response-related genes (IRGGs), resulting in the identification of differentially expressed inflammatory response-related genes (DIRRGs). Afterwards, we utilized the protein-protein interaction (PPI) network, machine learning algorithms, namely least absolute shrinkage and selection operator (LASSO) regression and random forest, to identify the signature markers. We employed a nomogram to evaluate the diagnostic effectiveness of the method, which has been confirmed through validation using GSE50223. qRT-PCR was used to confirm the expression of diagnostic genes in clinical samples. In addition, a consensus clustering method was employed to categorize patients with AR. Subsequently, extensive investigation was conducted to explore the discrepancies in gene expression, enriched functions and pathways, as well as potential therapeutic drugs among these distinct subtypes., Results: A total of 22 DIRRGs were acquired, which participated in pathways including chemokine and TNF signaling pathway. Additionally, machine learning algorithms identified NFKBIA, HIF1A, MYC, and CCRL2 as signature genes associated with AR's inflammatory response, indicating their potential as AR biomarkers. The nomogram based on feature genes could offer clinical benefits to AR patients. We discovered two molecular subtypes, C1 and C2, and observed that the C2 subtype exhibited activation of immune- and inflammation-related pathways., Conclusions: NFKBIA, HIF1A, MYC, and CCRL2 are the key genes involved in the inflammatory response and have the strongest association with the advancement of disease in AR. The proposed molecular subgroups could provide fresh insights for personalized treatment of AR., 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 © 2024 Dai, Xia, Huai, Li, Zhou, Wang and Chen.)

Blood samples are easily obtained from sheep. Therefore, blood analysis can be a convenient method for evaluating reproductive traits in sheep by detecting genetic and metabolic changes in the ovary. By combining 167 RNA sequencing data and 60 untargeted metabolomics data, this study analyzed the relationship between genes and metabolites in the ovary and blood. The conjoint KEGG enrichment analysis enriched glutathione (GSH) metabolic pathways both in the ovary and blood. This finding provides an explanation for possible GSH metabolic processes in the ovary with metabolite exchange in the blood. The metabolite-gene-disease interaction network revealed a correlation between the expression of certain Bardet-Biedl syndrome (BBS) family genes in the ovary and blood. This indicates that BBS family genes, such as BBS10 in sheep blood, could be a potential biomarker for BBS. We investigated the relationship between BBS10 gene expression in the ovary and lambing numbers using whole-genome sequencing data from 450 ewes. Our findings suggest that g.112314188C>G may lead to decreased litter size in ewes carrying the FecB gene. These single nucleotide polymorphisms could be potential molecular markers for breeding sheep., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Doxorubicin (DOX) is the classic soft tissue sarcomas (STS) first-line treatment drug, while dose-dependent myelosuppression and cardiotoxicity limit its application in clinic. This research intends to apply DOX, which is also an inducer of immunogenic cell death as a part for "in situ vaccination" and conjointly uses PD-1 inhibitors to enhance antitumor efficacy. In order to achieve the sustained vaccination effect and real-time monitoring of distribution in vivo, the in situ forming and injectable hydrogel platform with the function of visualization is established for local delivery. The hydrogel platform is synthesized by hyaluronic acid-dopamine coordinated with gadolinium ions (Gd 2+ ). Gd 2+ provides the ability of magnetic resonance imaging, meanwhile further cross-linking the hydrogel network. Experiments show excellent ability of sustained release and imaging tracking for the hydrogel platform. In mouse STS models, the "in situ vaccination" hydrogels show the best effect of inhibiting tumor growth. Further analysis of tumor tissues show that "in situ vaccination" group can increase T cell infiltration, promote M1-type macrophage polarization and block elevated PD-1/PD-L1 pathway caused by DOX. These results are expected to prove the potential for synthesized hydrogels to achieve a universal platform for "in situ vaccination" strategies on STS treatments., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Considering the low indoor positioning accuracy and poor positioning stability of traditional machine-learning algorithms, an indoor-fingerprint-positioning algorithm based on weighted k-nearest neighbors (WKNN) and extreme gradient boosting (XGBoost) was proposed in this study. Firstly, the outliers in the dataset of established fingerprints were removed by Gaussian filtering to enhance the data reliability. Secondly, the sample set was divided into a training set and a test set, followed by modeling using the XGBoost algorithm with the received signal strength data at each access point (AP) in the training set as the feature, and the coordinates as the label. Meanwhile, such parameters as the learning rate in the XGBoost algorithm were dynamically adjusted via the genetic algorithm (GA), and the optimal value was searched based on a fitness function. Then, the nearest neighbor set searched by the WKNN algorithm was introduced into the XGBoost model, and the final predicted coordinates were acquired after weighted fusion. As indicated in the experimental results, the average positioning error of the proposed algorithm is 1.22 m, which is 20.26-45.58% lower than that of traditional indoor positioning algorithms. In addition, the cumulative distribution function (CDF) curve can converge faster, reflecting better positioning performance.

Nosiheptide is a bicyclic thiopeptide featuring an indole-containing side ring, which is biologically important in maintaining its potent antibacterial activity. By using mutational biosynthesis, the pharmaceutically significant benzothiophene was introduced into the nosiheptide biosynthetic pathway, resulting in the generation of three bioactive nosiheptide analogues with characteristic benzothiophene-containing side rings. Insights were provided into the transformation relationship of these analogues, which effectively improves the yield of S-NOS- 1 with favorable activity against Gram-positive pathogens.

In this study, a portable electrochemiluminescence sensor chip was designed for trenbolone (TBE) trace detection in environmental water. First, a stable ECL signal was obtained with low-toxicity 3,4,9,10-perylenetetracarboxylic acid (PTCA) as a luminophore and persulfate (S 2 O 8 2- ) as a coreactant. Second, hollow-structured Cu 2 MoS 4 was introduced as a coreaction accelerator to catalyze S 2 O 8 2- reduction. The reversible conversion of the mixed-valence transition metal ions in Cu 2 MoS 4 (Cu + /Cu 2+ and Mo 4+ /Mo 6+ ) greatly promoted the generation of the sulfate radical (SO 4 •- ). Meanwhile, the special porous structure of Cu 2 MoS 4 possessed a large specific surface area, thus enhancing its catalytic performance. Based on these enhancement mechanisms, a strong ECL signal was acquired, which improved the detection sensitivity of the constructed sensor. Importantly, a microfluidic chip was introduced for sensing detection, thereby improving the practicality of the sensor. The developed sensor chip was miniature and portable, exhibiting high sensitivity for TBE detection with a wide linear range (10 fg/mL-100 ng/mL) and lower detection limit (3.32 fg/mL). This was of great significance for timely and rapid analysis of steroid pollutants in natural water.

Nanoarrays (NAs) with stable signal output have become the most promising photoelectrochemical (PEC) biosensing substrate. However, a general issue is that interfacial charge-carrier recombination in a single-component semiconductor cannot be easily prevented, resulting in a low photocurrent density. Herein, a biosensor utilizing a Ag-embedded TiO 2 -Ag 2 S nanojunction (TiO 2 -Ag-Ag 2 S) as a signal converter was developed for the detection of CD44 protein─a transmembrane glycoprotein highly expressed in breast cancer cells. The ternary Z-scheme heterojunction was prepared by a distinctive scheme in which the Ag layer is introduced onto the surface of rutile TiO 2 NAs by magnetron sputtering, whereas the Ag 2 S is rooted in the local sulfuration of Ag. With a sufficient density of oriented nanorods, TiO 2 -Ag-Ag 2 S exhibits a smooth photocurrent output and minimal variation among different batches; it is undoubtedly a satisfactory PEC sensing carrier, which enables highly specific identification of target CD44 on the surface of MDA-MB-231 cells due to DNA strand displacement reactions (SDRs) and host-guest recognition between hyaluronic acid (HA) and CD44. The biosensor shows a sensitive PEC response to CD44 over a wide range of 37 to 5.0 × 10 5 cells/mL. We can conclude that this approach will provide an alternative solution to breast cancer diagnosis.

Relying on the electrochemiluminescence (ECL) and microfluidic technology, an immunosensor chip with high bioactivity was designed for sensitive determination of cytokeratin 19 fragment 21-1 (CYFRA 21-1). The mesoporous nanomaterial Fe 3 O 4 @Cu@Cu 2 O as the co-reaction accelerator was used to catalyze the S 2 O 8 2- to produce more SO 4 •- to achieve the amplification of the ECL signal. In fact, the generating of SO 4 •- could not only be done with the aid of the reversible cycles of Fe 2+ and Fe 3+ and Cu + and Cu 2+ , but could be achieved also through the catalase-like function of Fe 3 O 4 . What is more, it has also been proved that Fe 3 O 4 @Cu@Cu 2 O exhibited better catalytic performance than single Fe 3 O 4 , Cu 2 O, and Cu@Cu 2 O, which supported its application in this system. In addition, a portable microfluidic immunosensor chip for CYFRA 21-1-sensitive determination was assembled, which showed high selectivity, sensitivity, and strong universality in clinical cancer screening and diagnosis. It should be noted that HWRGWVC (HWR) was introduced as the antibody fixator to improve the incubation and binding efficiency of the antibody, which increased the ECL intensity and improved the sensitivity of the immunosensor. This strategy provided a new idea for cancer identification and diagnosis in clinical medicine., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A signal-amplified electrochemiluminescent (ECL) sensor chip was developed for sensitive analysis of procalcitonin (PCT). Herein, we first prepared a self-enhanced luminophore, which enhanced ECL responses through intramolecular reactions. Second, Au-Pd bimetallic nanocrystals and mixed-valence Ce-based metal-organic frameworks (MOFs) were introduced as co-reaction promoters to facilitate the reduction of dissolved O 2 . Based on the synergistic catalysis of Au and Pd, the spontaneous cyclic reaction of Ce(III)/Ce(IV), and the high electrochemical active surface area of Ce(III, IV) MOF, a large number of superoxide anion radicals (O 2 •- ) and hydroxyl radicals (OH • ) were produced. Therefore, the luminescence efficiency of N -(aminobutyl)- N -(ethylisoluminol)-dissolved O 2 (ABEI-O 2 ) systems were greatly improved, providing a new prospect for the application of dissolved O 2 in ECL analysis. In addition, the affinity peptide ligands were used for the directional connection of antibodies to provide protection for the bioactivity of the proposed sensor. Finally, the microfluidic technology was applied to ECL analysis to integrate the three-electrode detection system into the self-assembled microfluidic chip, which realized the automation and portability of the detection process. The developed sensor showed high sensitivity for PCT detection with a detection limit of 3.46 fg/mL, which possessed positive significance for the clinical diagnosis of sepsis.

Objective: This study aims to determine outcomes and complications in functional reconstruction of soft tissue defects after surgical resection for soft tissue sarcomas (STSs) of extremities., Methods: A retrospective chart review was performed on patients with STSs of extremities from May 2015 to April 2019 who underwent radical resection of STSs and reconstruction of soft tissue defect with free vascularized anterolateral thigh flap (FVALTP). A minimum 3-month follow-up was required for all the patients. Patient demographics and comorbidities, flap characteristics, postoperative complications, and time to heal were recorded. The functional outcomes of the reconstructed limbs were assessed by the Musculoskeletal Tumour Society（MSTS） scoring system., Results: A total of 11 patients (four males and seven females) were included in the study. The mean age was 62 years (range: 29-84 years). The mean surface area was 151.4 cm 2 (range: from 64 cm 2 to 418cm 2 ). The mean operation time was 126 min (range: 95-296 min). The mean follow-up was 17.5 months (range: 6-34 months). The mean score of MSTS at last follow-up was 26.2 (range: 12-29). Incision healed by first intention in eight patients. Incision healed by second intention in three patients. A patient who had received preoperative radiotherapy experienced delayed union. After debridement, the patient successfully got union. Another two patients experienced marginal necrosis of flap due to vascular crisis. After 3-week dressing changes, the patients also got satisfactory union. One case suffered from vascular crisis during surgery in which the procedure was changed into skin grafting to cover resection site., Conclusion: FVALTP technique can be effectively applied to the reconstruction of soft tissue defect after STSs resection. The short-term follow-up indicated satisfactory functional outcome and low incidence of previously known complications. It was necessary to further validate its efficacy in reconstruction of soft tissue defect after malignant extremity soft tissue sarcoma resection., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Malignant Peripheral Nerve Sheath Tumor (MPNST) is a malignant mesenchymal tumor. The majority of MPNSTs are found in patients with neurofibromatosis type 1 (NF-1) who have a high-grade sarcoma. At the moment, there are just a few instances of low-grade MPNST caused by NF-1. We present a case of malignant transformation of NF-1 into low-grade MPNST in a patient with a long history of the disease. Multiple protruding masses with ulceration on the right shoulder and chest wall were discovered during physical examination. Complete tumor excision was done, followed by hematoxylin-eosin and immunohistochemical staining. A portion of the tumor had higher cellularity, hyperchromatic cell nuclei, and mitoses were seen in only five out of ten high-power fields. S-100 and vimentin were positive, whereas cytokeratin, desmin, SMA, and CD34 were negative. Ki-67 (MIB1) labeling index hot-spotting was around 25%. This was thought to be NF-1 malignant transformation into low-grade MPNST. Overall, knowing the clinical and pathologic characteristics of the disease, plus growing knowledge or experience with the condition, may improve preoperative diagnostic accuracy and extending survival time., Competing Interests: None., (IJCEP Copyright © 2021.)

Objective: To determine the expression of tyrosine protein kinase Met (c-MET), epidermal growth factor receptor (EGFR), and human epidermal growth factor receptor 2 (HER-2) in cases with gastric adenocarcinoma (GA)., Methods: The positive rates of the c-MET, EGFR, and HER-2 proteins between cancerous tissues and normal tissues sampled from 87 patients with GA were compared. The patients were assigned to different subgroups according to their clinicopathological characteristics and analyzed. Then the relationship between the above three indexes and the positive expression of Ki-67 were analyzed. In addition, the patients were assigned to positive and negative groups based on the situation of c-MET, EGFR and HER-2 proteins, and followed up for three years. These groups were compared in terms of recurrence-free survival, overall survival, and risks factors of prognosis., Results: The positive rates of c-MET, EGFR and HER-2 proteins in GA tissues were all higher than those in corresponding non-tumor tissues (all P<0.001), and the positive rates of them were greatly different in subgroups with different differentiation, invasion depth, TNM stage, lymph node metastasis (LNM), distant metastasis and presence of tumor thrombus (all P<0.05) and were positively correlated with the expression of Ki-67 protein (P<0.05). Moreover, the survival analysis results revealed lower recurrence-free survival and overall survival rates in groups with negative expression of c-MET, EGFR, and HER-2 than those in groups with positive expression of them (both P<0.001). Furthermore, the positive EGFR was an independent prognostic factor affecting the survival of patients with GA., Conclusion: The expression of c-MET, EGFR and HER-2 proteins is correlated with clinical characteristics of patients with GA, and patients with positive expression of them face a higher recurrence rate. Additionally, EGFR protein may affect patients' survival., Competing Interests: None., (AJTR Copyright © 2021.)

The aim of the present study was to investigate the neuroprotective effects of naringin on the memory impairment of hydrocortisone mice, and to elucidate the potential underlying molecular mechanisms. In the present study, a hydrocortisone model was constructed. Novel object recognition, Morris water maze and step‑down tests were performed in order to assess the learning and memory abilities of mice. Hematoxylin and eosin staining was used to observe pathological changes in the hippocampus and hypothalamus. Transmission electron microscopy was used to observe the ultrastructural changes in the hippocampus. Immunohistochemistry was used to detect the expression of ERα and ERβ. Western blotting was performed to detect the expression of each protein in the relevant system. It was found that naringin can significantly improve cognitive, learning and memory dysfunction in mice with hydrocortisone memory impairment. In addition, naringin can exert neuroprotective effects through a variety of mechanisms, including amyloid β metabolism, Tau protein hyperphosphorylation, acetylcholinergic system, glutamate receptor system, oxidative stress and cell apoptosis. Naringin can also affect the expression of phosphorylated‑P38/P38, indicating that the neuroprotective effect of naringin may also involve the MAPK/P38 pathway. The results of the present study concluded that naringin can effectively improve the cognitive abilities of mice with memory impairment and exert neuroprotective effects. Thus, naringin may be a promising target drug candidate for the treatment of Alzheimer's disease.

Acetylcholinesterase (AChE) is a key enzyme used to detect organophosphorus pesticide residues by the enzyme inhibition method. An accidental discovery of a mutant strain with AChE activity was made in our laboratory during the process of AChE expression by Pichia pastoris . The pPIC9K- Drosophila melanogaster acetylcholinesterase ( DmAChE ) -like expression vector was constructed by codon optimization of this mutant strain, which was transformed into P. pastoris GS115, and positive clones were selected on yeast peptone dextrose (YPD) plate with G418 at 4.0 mg/mL. The GS115-pPIC9K- DmAChE-like strain was subjected to 0.5% methanol induction expression for 120 h, with a protein band at 4.3 kDa found by the tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) pattern of the fermentation supernatant. After preliminary purification by ammonium sulfate precipitation, the enzyme activity was detected to be 76.9 U/(mL⋅min). In addition, the pesticide sensitivity test proved that DmAChE-like is selective and sensitive to organophosphorus pesticides.

The frequent and inappropriate use of antibiotics aggravate the variation and evolution of multidrug-resistant bacteria, posing a serious threat to public health. Nosiheptide (NOS) has excellent lethality against a variety of Gram-positive bacteria, however the physical and chemical drawbacks hamper its routine application in clinical practice. In this study, by using NOS as the starting material, a total of 15 NOS analogues (2a-4e) were semi-synthesized via its dehydroalanine residue reacting with monosubstituted anilines. In vitro antimicrobial susceptibilities of NOS and its analogues against two methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) clinical isolates were determined by broth microdilution assay to determine the minimum inhibitory concentration (MIC). Antimicrobial susceptibility testing data shown that most of the NOS analogues had a better antibacterial effect than the parent compound, with compound 3c exhibiting the highest antibacterial activity against VRE (MIC = 0.0078 mg/L) and MRSA (MIC < 0.0039 mg/L). Molecular docking of synthetic compounds was also performed to verify the binding interactions of NOS analogues with the target. Our data indicated that compound 3c possesses stronger and more complex intermolecular force than other analogues, which is consistent with the results of the biological activity evaluation. Overall, this study identified a number of potential antibacterial NOS analogues that could act as potent therapeutic agents for multidrug-resistant bacterial infections., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Nosiheptide (NOS) is a member of bicyclic thiopeptides possessing a biologically important indolic acid (IA) moiety appended onto the family-characteristic core system. The IA formation relies primarily on NosL, a radical S-adenosylmethionine (SAM) protein that catalyzes a complex rearrangement of the carbon side chain of l-tryptophan, leading to the generation of 3-methyl-2-indolic acid (MIA). Here, we establish an efficient mutational biosynthesis strategy for the structural expansion of the side-ring system of NOS. The nosL-deficient mutant Streptomyces actuosus SL4005 complemented by chemically feeding 6-fluoro-MIA is capable of accumulating two new products. The target product 6'-fluoro-NOS contains an additional fluorine atom at C6 of the IA moiety, in contrast with an unexpected product 6'-fluoro-NOSint that features an open side ring and a bis-dehydroalanine (Dha) tail. The newly obtained 6'-fluoro-NOS displayed equivalent or slightly reduced activities against the tested drug-resistant pathogens compared with NOS, but dramatically decreased water solubility compared with NOS. Our results indicate that the modification of the IA moiety of NOS not only affects its biological activity but also affects its activity which will be key considerations for further modification.

Objective: To determine the clinical outcome and complications associated with use of free vascularized fibular graft (FVFG) in the resection and reconstruction of extremity osteosarcoma (OS)., Methods: This is a retrospective study recruiting a consecutive series of 18 patients who had undergone resection of extremity OS between May 2009 and June 2017 in our clinic center. Reconstruction of the bone defect with FVFG was performed for each patient. Surgery-related complications and time of bone union were recorded at the follow-up visit. The functional outcome of the reconstructed limb was assessed with the musculoskeletal tumor society (MSTS) scoring system. Patients were further classified into low extremity group and upper extremity group according to the tumor location. The Student t-test was used to compare the surgical outcome between the two subgroups., Results: There were 11 males and seven females with an average age of 25.9 ± 14.2 years. The mean length of the bone resection was 11.9 ± 4.1 cm. The mean follow-up duration was 3.1 ± 1.2 years. As for tumor location, six cases were located in the femur, five in the tibia, four in the humerus, two in the ulna, and one in the radius. All the patients had successful graft healing at an average of 4.9 months after surgery. At the 2-year follow-up, an excellent functional outcome was observed in 88.9% of the patients (n = 16). The mean score of MSTS was 27.0 ± 4.6. Screw loosening and autograft fracture were observed in one patient with femur tumor, who had a low MSTS score of 11. Besides, there were three cases with delayed incision healing. Patients with lower extremity OS were found to have significantly longer duration of hospital stay and more blood loss than those with upper extremity OS. The incidence of postoperative complication was higher in the lower extremity group but with marginal significance (0% vs 36.3%, P = 0.1). There was no significant difference regarding time to bone union and the functional outcome as indicated by MSTS score., Conclusions: FVFG technique can be effectively applied to the reconstruction of bone defects after OS resection with satisfactory functional outcome and low incidence of complications., (© 2020 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Osteosarcoma is the most common bone tumor affecting both adolescents and children. Early detection is critical for the effective treatment of the disease. Derived from cancer cells, miR‑21 contained within exosomes in the tumor microenvironment may act on both cancer cells and the surrounding tumor microenvironment (TME), including immune cells, endothelial cells and fibroblasts. In human serum and plasm, the level of exosomal miR‑21 between osteosarcoma patients and healthy controls differs, supporting the role of miR‑21 as a biomarker for osteosarcoma. The involvement of a number of miR‑21 target genes in tumor progression suggests that miR‑21 may significantly affect the plasticity of cancer cells, leading to tumor progression, metastasis, angiogenesis and immune escape in osteosarcoma. Understanding the biogenesis and functions of exosomal miR‑21 is of great value for the diagnosis and therapy of cancer, including osteosarcoma. The present review discusses the role of miR‑21 in the tumor microenvironment, and in the development and progression of osteosarcoma, with an aim to summarize the functions of this miRNA in cancer.

Background: Human epidermal growth factor receptor 2 (HER2)-mutant lung cancer remains an orphan of specific targeted therapy. The variable responses to anti-HER2 therapies in these patients prompt us to examine impact of HER2 variants and co-mutations on responses to anti-HER2 treatments in lung cancer., Patients and Methods: Patients with stage IV/recurrent HER2-mutant lung cancers identified through next-generation sequencings were recruited from seven hospitals. The study comprised a cohort A to establish the patterns of HER2 variants and co-mutations in lung cancer and a cohort B to assess associations between HER2 variants, co-mutations, and clinical outcomes., Results: The study included 118 patients (cohort A, n = 86; cohort B, n = 32). Thirty-one HER2 variants and 35 co-mutations were detected. Predominant variants were A775&#95;G776insYVMA (49/118, 42%), G778&#95;P780dup (11/118, 9%), and G776delinsVC (9/118, 8%). TP53 was the most common co-mutation (61/118, 52%). In cohort B, objective response rates with afatinib were 0% (0/14, 95% confidence interval [CI], 0%-26.8%), 40% (4/10, 14.7%-72.6%), and 13% (1/8, 0.7%-53.3%) in group 1 (A775&#95;G776insYVMA, n = 14), group 2 (G778&#95;P780dup, G776delinsVC, n = 10), and group 3 (missense mutation, n = 8), respectively (p = .018). Median progression-free survival in group 1 (1.2 months; 95% CI, 0-2.4) was shorter than those in group 2 (7.6 months, 4.9-10.4; hazard ratio [HR], 0.009; 95% CI, 0.001-0.079; p < .001) and group 3 (3.6 months, 2.6-4.5; HR, 0.184; 95% CI, 0.062-0.552; p = .003). TP53 co-mutations (6.317; 95% CI, 2.180-18.302; p = .001) and PI3K/AKT/mTOR pathway activations (19.422; 95% CI, 4.098-92.039; p < .001) conferred additional resistance to afatinib., Conclusion: G778&#95;P780dup and G776delinsVC derived the greatest benefits from afatinib among HER2 variants. Co-mutation patterns were additional response modifiers. Refining patient population based on patterns of HER2 variants and co-mutations may help improve the efficacy of anti-HER2 treatment in lung cancer., Implications for Practice: Human epidermal growth factor receptor 2 (HER2)-mutant lung cancers are a group of heterogenous diseases with up to 31 different variants and 35 concomitant genomic aberrations. Different HER2 variants exhibit divergent sensitivities to anti-HER2 treatments. Certain variants, G778&#95;P780dup and G776delinsVC, derive sustained clinical benefits from afatinib, whereas the predominant variant, A775&#95;G776insYVMA, is resistant to most anti-HER2 treatments. TP53 is the most common co-mutation in HER2-mutant lung cancers. Co-mutations in TP53 and the PI3K/AKT/mTOR pathway confer additional resistance to anti-HER2 treatments in lung cancer. The present data suggest that different HER2 mutations in lung cancer, like its sibling epidermal growth factor receptor, should be analyzed independently in future studies., (© AlphaMed Press 2019.)

We herein report the functionalization of α-C-H in alcohols through cross-dehydrogenative coupling reactions. Selectfluor was used as a mild oxidant. In situ -generated HF participated in the reaction and no external strong acid was necessary. A variety of heteroaryl-substituted alcohols were achieved with good yields and with good functional group tolerance., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objectives: Previous genome-wide association study showed that GLDC/IL33 loci were associated with overall survival in patients with osteosarcoma (OS). We performed a replication study to explore whether variants of GLDC/IL33 are associated with the survival of OS patients and to further verify their functional role in the gene expression., Methods: A total of 216 patients with OS were enrolled. The overall survival time was calculated from the date of diagnosis till the date of last follow-up or mortality. Two SNPs were genotyped, including rs55933544 and rs74438701. OS specimens were obtained from 72 patients during surgery. The gene expression level of IL33 and GLDC was evaluated by qPCR. Patients were classified into two groups according to the 5-year overall survival (death/survival). The chi-square test was used to analyze difference of genotype frequency. The Student t -test was used to compare the gene expression level between different genotypes. Cumulative survival time was calculated by the Kaplan-Meier method and analyzed by the log-rank test., Results: Genotype TT of rs55933544 was significantly associated with the event of death (0.176 vs. 0.061, p  < 0.001). Patients with no risk allele T of rs55933544 showed a 5-year overall survival of 81.4% (110/141), which was significantly higher than an overall survival of 55.0% (29/54) for patients with one risk allele and 44.8% (12/21) for patients with two risk alleles ( p  < 0.01). Genotype TT of rs55933544 were indicative of remarkably lower expression of IL33 than genotype CC (0.00041 ± 0.00025 vs. 0.00065 ± 0.00031, p  = 0.04). Patients with low IL33 expression presented remarkably worse survival as compared with the patients with high IL33 expression ( p  < .01)., Conclusions: Variant rs55933544 was associated with the survival time of OS patients. IL33 may contribute to a poor prognosis of OS. Further investigation into the biological mechanisms by which IL33 influences the overall survival can shed light on the improvement of clinical outcome for OS patients., Competing Interests: No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript., (© 2019 Published by Elsevier GmbH.)

A cobalt and copper catalyzed reaction protocol has been developed to achieve the oxidative C-H/N-H annulation of benzamides containing an 8-aminoquinoline moiety as the directing group with ketones. Structurally diverse isoindolin-1-ones were furnished by the reaction of various substituent benzamides with ketones.

The sleep quality of patients with osteosarcoma (OS) was poorly understood. We aimed to evaluate the prevalence of sleep dysfunction in adolescent patients with OS using the Pittsburgh Sleep Quality Index (PSQI) and to further investigate the psychometric properties of the PSQI in this cohort of patients. Fifty four adolescent patients with OS who underwent chemotherapy treatment in our clinic centre were included. Sleep quality was assessed with the Chinese PSQI. Cronbach's alpha was calculated to evaluate the internal consistency. The confirmatory factor analysis (CFA) was used to determine the fitness of a two-factor structure. Sleep disturbance was observed in 57.4% (31/54) of the patients. Patients with the presence of metastasis or more than 2 cycles of chemotherapy were found to have remarkably higher median global score. The overall Cronbach's alpha was 0.87. The CFA showed an overall comparative fit index of 0.97, a root mean square error of approximation of 0.06 and a standardised root mean square residual of 0.07 respectively. PSQI was a reliable instrument to evaluate the sleep quality of adolescent patients with OS. Over half of the patients may experience sleep disturbance during the treatment. Early psychological interventions were recommended to improve the sleep quality of the patients., (© 2019 John Wiley & Sons Ltd.)

NosN is a radical S-adenosylmethionine protein observed in the biosynthesis of the bicyclic thiopeptide nosiheptide. Insights are provided in terms of the timing of NosN action, its catalytic mechanism, and its role in side ring formation. Beyond being a methyltransferase, NosN transforms a polythiazolyl peptide intermediate by functionalizing the S-conjugated indolic moiety to selectively build a C1 unit, form an ester linkage to the thiopeptide framework, and establish the side ring system specific for nosiheptide.

Variant rs7034162 in NFIB was reported to be associated with metastasis of osteosarcoma in European cases with genome-wide significance. Our purpose was to replicate the association of rs7034162 with the metastasis of osteosarcoma in the Chinese population and to further characterize the expression level of NFIB in osteosarcoma tissues. A total of 321 patients were included in this study. Variant rs7034162 was genotyped for each patient using the Taqman genotyping assay. Fifty-two cases of tumor tissues and adjacent normal tissues were collected during surgery. The χ 2 test was used to investigate the association of rs7034162 with the metastasis of osteosarcoma. The Student t test was used to compare the gene expression between patients with metastasis and those without metastasis. The messenger RNA expression level of NFIB was then compared among different genotypes of rs7034162 with 1-way analysis of variance test. Ninety-three patients were found to have metastasis. Patients with genotype AA had remarkably higher incidence of metastasis than those with genotype TT (34.4% vs 17.1%, P = .002). Patients with metastasis were found to have significantly higher rate of allele A than those without metastasis (53.2% vs 43.9%, P = .03). The messenger RNA expression of NFIB was significantly lower in tumor tissues of patients with metastasis than in those without metastasis (0.00035 ± 0.00017 vs 0.00063 ± 0.0025, P < .001). Compared to patients with genotype TT, those with genotype AA had remarkably decreased expression of NFIB (0.00033 ± 0.0014 vs 0.00067 ± 0.00037, P = .01). Single-nucleotide polymorphism rs7034162 was associated with metastasis of osteosarcoma in the Chinese population possibly via downregulation of NFIB . Further network analyses revealing the related pathways can help elucidate the molecular mechanism of distant metastasis in patients with osteosarcoma.

NUT carcinoma (NC) is an aggressive squamous tumor characterized by NUT gene rearrangement, and the most common fusion form is BRD4-NUT. However, NC diagnosis is difficult for its rareness and often being confused with a variety of poorly differentiated tumors. A 21-year-old Chinese woman was referred to our hospital for cough and intermittent fever. Chest computed tomography (CT) imaging revealed a left lobe hilar mass. Fiberoptic bronchoscopy results showed that tumor cells were poorly differentiated. In combination with immunohistochemistry staining, she was misdiagnosed with Ewing's sarcoma/primitive neuroectodermal tumor. Next-generation sequencing (NGS) revealing BRD4-NUT fusion, and NUT immunohistochemistry confirmed the diagnosis of NC. Subsequently, left pneumonectomy and lymph node dissection were performed, and the patient received pemetrexed and lobaplatin treatment. NGS technology played an important role in NC diagnosis in this case, and it may have clinical use for rare cancer diagnosis and guidance of potential targeted therapies.

The reaction of trifluoromethylated tertiary bromides with isonitriles induced by visible light is reported. Defluorination was avoided in a radical process. This method provides an efficient approach to compounds containing a trifluoromethylated quaternary carbon center, most of which show excellent potential to be agrochemicals. In addition, the bromides were prepared from perfluoroisobutylene, which is a waste from industry, after several steps. This reaction shows a feasible transfer of harmful waste into useful compounds.

Background: GIT1, a scaffold protein with ubiquitous multi-domain, is involved in many cellular processes. In recent years, it was proved that GIT1 participated in various tumors' growth or metastasis. However, the biological function of GIT1 in osteosarcoma is still unclear. In this study, we aimed to investigate the role and mechanism of GIT1 in osteosarcoma., Materials and Methods: Human osteosarcoma tissues were obtained to investigate the distribution of GIT1. Adequate osteosarcoma cells were stably infected with lentivirus to knockdown GIT1 level and then was used to carry out cell invasion and vascular endothelial growth factor (VEGF) assay in vitro. Orthotopic femoral osteosarcoma model was constructed to investigate the growth, invasion, and angiogenesis in vivo. Western blot was used to detect extracellular signal-regulated kinase (ERK1/2) activation and hypoxia-inducible factor-1 (HIF-1α) expression., Results: In this study, we found that GIT1 was distributed in human osteosarcoma tissues and highly expressed in osteosarcoma (OS) cells. Knockdown of GIT1 inhibited cell invasion and VEGF release in vitro and suppressed tumor growth, invasion, and angiogenesis in vivo. Furthermore, knockdown of GIT1 substantially downregulated the protein levels of p-ERK and HIF-1α in OST cells and inhibition of p-ERK by PD98059 could significantly decrease the expression of HIF-1α and concentration of VEGF in GIT1-shRNA-treated cells., Conclusion: GIT1 knockdown can effectively inhibit the growth, invasion, and angiogenesis of osteosarcoma. Thus, GIT1 might act as an oncogenic factor in osteosarcoma and could be a potential molecular target for osteosarcoma gene therapy., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Difluoromethylthiolation of aryldiazonium salts under photocatalytic conditions with a shelf-stable, easily prepared and inexpensive reagent, PhSO2SCF2H was described. A variety of difluoromethylthioethers were obtained utilizing aryldiazonium salts containing different functional groups. Aryldiazonium salts with a heteroarene moiety were tolerated. Fluorescence quenching experiments indicated that both oxidative and reductive quenching cycles occurred during this process.

Background: The role of Methylene tetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in the efficacy and toxicity of MTX-based therapy remains uncertain. Our purpose was to clarify whether these two polymorphisms are associated with the outcome of chemotherapy in a cohort of Chinese osteosarcoma (OS) patients treated by high-dose MTX., Methods: 109 OS patients who had sequentially received high-dose MTX therapy were included in this study. Plasma MTX level was measured routinely at 0, 24, 48 and 72 h after the administration of MTX. Two variants of MTHFR were genotyped using TaqMan SNP Genotyping Assay, including rs1801133 (C667T) and rs1801131 (A1298C). The extent of toxicity induced by MTX, including hematological toxicity, hepatic toxicity, renal toxicity and mucositis, was scored from grade 1 to 4. Severe toxicity was defined as a grade score of ≥3. Patients were dichotomized as follows: grade <3 or ≥3 for toxicity, and ≤0.2 µmol/L or >0.2 µmol/L for plasma MTX level at 72 h. The frequencies of genotypes and allele were compared between the dichotomized groups with the Chi-square test., Results: 24.8% (27/109) of the patients were found to have significantly high plasma MTX level at the 72 h. Patients with high MTX level at 72 h were found to have significantly higher frequency of genotype TT of rs1801133 (p = 0.002). As for rs1801131, no significant association was found with plasma MTX level. Patients with severe hepatic toxicity or mucositis were found to have remarkably higher incidence of genotype TT of rs1801133 than those with mild toxicity (33.3% vs. 14.8%, p = 0.04 for hepatic toxicity; 34.8% vs. 19.8%, p = 0.05 for mucositis)., Conclusions: Variant rs1801133 was confirmed to have remarkable influence on the MTX-induced toxicity. We recommend identification of the genotype of MTHFR variant prior to the application of high-dose MTX to OS patients, which could be an important predictor to screen severe toxicities and thus improve treatment outcomes.

Exosomes are extracellular vesicles with diameters of 30-100 nm that are key for intercellular communication. Almost all types of cell, including dendritic cells, T cells, mast cells, epithelial cells, neuronal cells, adipocytes, mesenchymal stem cells, and platelets, can release exosomes. Exosomes are present in human body fluids, such as urine, amniotic fluid, malignant ascites, synovial fluid, breast milk, cerebrospinal fluid, semen, saliva, and blood. Exosomes have biological functions in immune response, antigen presentation, intercellular communication, and RNA and protein transfer. This review provides a brief overview of the origin, morphological characteristics, enrichment and identification methods, biological functions, and applications in tissue engineering and neurological diseases of exosomes.

Objectives: Previous pharmacogenetics studies showed that genetic variants could be indicative of the response to chemotherapy. We aimed to investigate whether variants of FasL, MSH2, ABCC5, CASP3 and CYP3A4 are associated with the outcome after chemotherapy-based treatment in osteosarcoma., Methods: 132 osteosarcoma patients who had completed the neoadjuvant chemotherapy in our center were included. 5-year progression-free survival (PFS) was assessed from the initial treatment to the earliest sign of disease progression or death from any cause. 5 SNPs were genotyped using TaqMan SNP Genotyping Assay, including rs763110 of FasL, rs4638843 of MSH2, rs939338 of ABCC5, rs2720376 of CASP3 and rs4646437 of CYP3A4. Patients were classified into two groups according to the 5-year PFS (event/no event). The chi-square test was used to analyze difference of genotype frequency. Logistic regression analysis was used to determine the independent predictors of the PFS rate., Results: The overall 5-year PFS was 61.4% (81/132). Genotype TT/CT of rs763110 and genotype GG/AG of rs939338 were significantly associated with the event of 5-year PFS ( p  = 0.028 for rs763110; p  = 0.039 for rs939338). Patients with no risk allele showed a 5-year PFS of 73.7% (42/57), which was significantly higher than a PFS of 54.2% (26/48) for patients with one risk allele and 48.1% (13/27) for patients with two different risk alleles ( p  = 0.03). Logistic regression analysis showed that allele T of FasL rs763110 and allele G of ABCC5 rs939338 were independent risk factors of the 5-year PFS. The ORs were 2.14 (95%CI = 1.13-3.35, p  = 0.01) for rs763110 and 1.73 (95%CI = 1.05-2.52, p  = 0.03) for rs939338, respectively., Conclusions: The association of variants of FASL and ABCC5 with survival outcome after chemotherapy was validated in patients with osteosarcoma. Our findings may provide a new insight into a more personalized treatment for patients with osteosarcoma.

Rh(III)-catalyzed C(sp 3 )-H bond aminocarbonylation of 8-methylquinolines and isocyanates has been realized under mild conditions. This approach is applicable to different aryl and alkyl isocyanates, leading to the synthesis of various α-quinolinyl amide compounds in moderate to excellent yields. A plausible mechanism for this transformation is proposed according to the experimental results obtained.

The molecular mechanisms underlying the development of osteosarcoma (OS) are not fully understood. In this study, we investigated for the first time the clinical significance and biological activity of centrosomal protein 55 (CEP55) in OS. We found that CEP55 was overexpressed in OS, and the CEP55 expression level in OS was correlated with metastasis and poor prognosis. Through in vitro experiments, we confirmed that CEP55 knockdown significantly induced cell cycle arrest at G1 phase and suppressed OS cell proliferation, migration and invasion. In addition, CEP55 knockdown suppressed OS tumour growth in nude mice. Global gene expression profiling of CEP55-silenced MNNG/HOS cells showed that the AKT pathway might be involved in the regulation of OS cell activity. Two downstream factors of AKT signalling, CCND1 and FN1, were found to have significantly higher expression in tumour tissues, and their mRNA expression levels were strongly correlated with CEP55 expression. To conclude, our data suggest that CEP55 can be used as a prognostic marker for OS, highlighting the significance of CEP55 signalling as a putative therapeutic target.

Background: To investigate the effectiveness of tibiotalocalcaneal arthrodesis with a retrograde nail and allograft in limb salvage surgery for patients with distal tibia osteosarcoma., Methods: 5 patients diagnosed as distal tibia osteosarcoma underwent ankle arthrodesis with a retrograde nail in our hospital. During the follow-up, radiographic views of the ankle joint were taken in two planes to assess bone healing and axis alignment. Other measurements of outcomes included procedure-related complications, local recurrence, and metastasis. Functional outcomes were evaluated with the Musculoskeletal Tumor Society (MSTS) scoring system., Results: Postoperative complications occurred in 4 patients, including 4 cases of mild subcutaneous fluid and 1 case of screw breakage. All patients showed stable ankle and could stand or walk with the assistance of crutch before the complete union between allograft and host bone. One patient died due to multiple bone and pulmonary metastasis at 1 year after surgery. As for the other 4 patients, they were followed-up regularly for a mean period of 42 months. No local recurrence or distant metastasis occurred in any of these four patients. All the 4 patients expressed satisfaction with the outcome. According to MSTS scale, the mean postoperative functional score was 74.3%±4.4% (range, 70%-81%)., Conclusions: Intramedullary retrograde nail for distal tibia osteosarcoma could produce a satisfactory outcome in terms of functional results and complications. Excellent stabilization of the ankle joint can be achieved through this technique, as it allows patients to perform much earlier postoperative weight-bearing exercise., (Copyright © 2017 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

The present study aimed to isolate and characterize side population (SP) cells in the human lung cancer A549 cell line, and elucidate the molecular mechanism of SP cells underlying lung cancer. The SP and non-SP (NSP) cells in A549 cells were isolated and their differentiation was analyzed by fluorescence-activated cell sorting. An in vitro plate clone assay, Matrigel ® Transwell assay and chemoresistance analysis of the sorted SP and NSP cells were performed. In addition, the sorted SP and NSP cells were injected into BALB/c nude mice to detect their tumorigenic potential in vivo . The expression of ATP-binding cassette sub-family G member 2 (ABCG2) in transplanted tumors was detected by immunohistochemistry. The SP and NSP cells were successfully isolated. The results demonstrated that SP cells accounted for 1.09% of live A549 cells. SP cells produced SP and NSP cells, while NSP cells only produced NSP cells. In addition, SP cells formed more colonies, exhibited improved invasive ability and increased levels of chemoresistance compared with NSP cells in vitro . SP cells demonstrated a higher tumorigenic potential in BALB/c nude mice, and the number of ABCG2-positive cells in the SP xenograft tumors were significantly increased compared with that in the NSP xenograft tumors. The present study indicated that SP cells isolated from the human lung cancer A549 cell line demonstrated increased tumorigenicity, and improved invasive ability and chemoresistance compared with NSP cells. In addition, detection of ABCG2 expression may assist in predicting the chemotherapeutic outcome of patients, and serve as a target for treating lung cancer.

Background: Previous studies showed that genetic variant rs145204276 in the promoter region of GAS5 was associated with the development of human cancer including colorectal cancer and hepatocellular cancer. This study aimed to investigate the role of rs145204276 in the development of osteosarcoma (OS)., Methods: 132 OS patients and 1270 healthy controls were recruited for the genotyping analysis of rs145204276. Promoter methylation level of GAS5 was determined for all patients. The tumor tissues and the adjacent normal tissue were collected from 42 patients during surgery and the relative expression of GAS5 was then quantified by Real-time PCR. The Chi-square test was used to determine the difference of genotype and allele frequency between the patients and the controls. The gene expression and the percentage of methylation alleles were compared among different genotypes of rs145204276 with One-way ANOVA test., Results: Compared with the controls, patients were found to have significantly lower rate of genotype del/del (7.6% vs. 8.7%, p = 0.024). The frequency of allele del was significantly lower in the patients than in the controls (23.5% vs. 30.1%, p = 0.021). Compared with than patients with genotype ins/ins, those with genotype del/del had remarkably higher expression of GAS5 (0.0033 ± 0.0019 vs. 0.0018 ± 0.0006, p < 0.001). Patients with genotype del/del were found to have obviously hypermethylation at the 7th CpG site as compared with those with genotype ins/ins (38.7% ± 21.1% vs. 20.5% ± 8.2%, p < 0.001)., Conclusions: The genetic variant rs145204276 is functionally associated with the susceptibility of OS, which can function as a protective factor in the incidence of OS possibly through the regulation of GAS5.

Objective: The purpose of this study was to characterize diffusion tensor imaging (DTI) features of lumbar vertebras in adolescent idiopathic scoliosis (AIS) patients., Methods: Fifty-two AIS patients and 20 healthy volunteers underwent 3-T magnetic resonance scanning including DTI sequence. The fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values on the convex and concave sides of lumbar vertebras were obtained and compared., Results: The FA and ADC values differed significantly between the convex and concave side of lumbar vertebras in AIS (P < 0.01). The ADC values in AIS differed significantly with healthy volunteers (P < 0.01). The FA values on the convex side of L1 to L2 were significantly lower than L4 to L5 in AIS. The difference of FA values between the concave and convex sides of the apex vertebra correlated significantly with Cobb angle (r = 0.436, P < 0.01)., Conclusions: The convex and concave sides of lumbar vertebras in AIS patients showed different DTI features.

Objective: To compare the clinical effects of modified uvulopalatopharyngoplasty (UPPP) with low-temperature plasma with selective nasal cavity vasodilatation with tongue volume reduction for obstructive sleep apnea/hypopnea syndrome (OSAHS)., Methods: A retrospective analysis based on 156 patients with serious OSAHS was used for the evaluation. These patients were divided into 2 groups according to surgery methods according to 1:1.s. The patients in observation group accepted modified UPPP with low-temperature plasma and selective nasal cavity vasodilatation with tongue root volume reduction on the basis of fully preparation for surgery, while the patients in the control group accepted normal treatment. The clinic effects, operative complications, postoperative relapse, and other indexes were compared., Result: After 6 months of follow-up visit, the general effective rates of the observation group and control groups were 80.77% and 61.54%, the difference was statistically significant (P < 0.05). Besides, the rate complication occurrence in the observation group was also lower than that in the control group., Conclusion: The effect of modified UPPP with low-temperature plasma and selective nasal cavity vasodilatation with tongue volume reduction is satisfactory for patients with moderate and severe OSAHS after enough preparation.

A pair of enantioselective switchable bifunctional catalysts are shown to promote a range of conjugate addition reactions in up to 95 : 5 e.r. and 95% conversion. Each catalyst can be switched OFF using conditions that switch the other catalyst ON. Catalyst ON : OFF ratios of up to 98 : 2 and 1 : 99 were achieved, with a ratio of reaction rates of up to 16 : 1 between the ON and OFF states, maintained over complete ON-OFF-ON and OFF-ON-OFF cycles. However, simultaneous operation of the catalyst pair in the same reaction vessel, which in principle could allow product handedness to be switched by simple E - Z isomerisation of the catalyst pair, was unsuccessful. In this first generation complementary pair of enantioselective switchable organocatalysts, the OFF state of one catalyst inhibits the ON state of the other.

Aim: Recurrence of giant cell tumor of bone (GCTB) in the soft tissue is rarely seen in the clinical practice. This study aims to determine the prevalence of soft tissue recurrence of GCTB, and to characterize its radiographic features., Methods: A total of 291 patients treated by intralesional curettage for histologically diagnosed GCTB were reviewed. 6 patients were identified to have the recurrence of GCTB in the soft tissue, all of whom had undergone marginal resection of the lesion. Based on the x-ray, CT and MRI imaging, the radiographic features of soft tissue recurrence were classified into 3 types. Type I was defined as soft tissue recurrence with peripheral ossification, type II was defined as soft tissue recurrence with central ossification, and type III was defined as pure soft tissue recurrence without ossification. Demographic data including period of recurrence and follow-up duration after the second surgery were recorded for these 6 patients. Musculoskeletal Tumor Society (MSTS) scoring system was used to evaluate functional outcomes., Results: The overall recurrence rate was 2.1% (6/291). The mean interval between initial surgery and recurrence was 11.3 ± 4.1 months (range, 5-17). The recurrence lesions were located in the thigh of 2 patients, in the forearm of 2 patients and in the leg of the other 2 patients. According to the classification system mentioned above, 2 patients were classified with type I, 1 as type II and 3 as type III. After the marginal excision surgery, all patients were consistently followed up for a mean period of 13.4 ± 5.3 months (range, 6-19), with no recurrence observed at the final visit. All the patients were satisfied with the surgical outcome. According to the MSTS scale, the mean postoperative functional score was 28.0 ± 1.2 (range, 26-29)., Conclusions: The classification of soft tissue recurrence of GCTB may be helpful for the surgeon to select the appropriate imaging procedure to detect the recurrence. In addition, the marginal resection can produce a favorable outcome for the patients.

Background: The Musculoskeletal Tumor Society (MSTS) scoring system is a disease-specific instrument to determine the physical and mental health for patients with extremity sarcoma. This study aims to investigate the reliability and validity of the Chinese version of the MSTS, and to evaluate functional outcomes of the surgical treatment of lower extremity sarcoma using the Chinese MSTS., Methods: A cohort of 98 patients who had undergone surgery for lower extremity sarcoma were included. All the patients completed the clinical assessment with the Chinese MSTS and the Chinese Toronto Extremity Salvage Score (TESS). Assessment of psychometric properties was carried out through reliability and validity test. The reliability of Chinese MSTS was evaluated through test-retest analysis, inter-observer analysis and internal consistency. The inter-observer and test-retest reliability was analyzed with intra-class correlation coefficient (ICC). The internal consistency was evaluated by Cronbach's α, with a value >0.70 considered acceptable. The discriminant validity was evaluated through comparison of the MSTS score between patients undergoing amputation surgeries and those undergoing limb-salvage surgeries. The construct validity was evaluated with the factor analysis., Results: The mean MSTS score was 21.5 ± 7.1. The ICC was 0.91 (95% confidence interval (CI) = 0.85-0.96) for the test-retest reliability and 0.90 (95% CI = 0.86-0.93) for the inter-observer analysis. The test for internal consistency showed a Cronbach's α of 0.86 for the MSTS. Patients undergoing amputation surgery had remarkably lower MSTS score than patients undergoing limb-salvage surgeries (18.8 ± 5.4 vs. 23.5 ± 6.3, p = 0.005), which indicated a good discrinimant validity of the Chinese MSTS. The factor analysis indicated a 1-factor model with acceptable goodness of fit., Conclusions: The Chinese MSTS scoring system is a reliable and valid instrument with well-accepted psychometric properties. Through application of the Chinese MSTS, we demonstrated that patients receiving limb-salvage surgeries may have better functional outcome and QoL than those undergoing amputation surgeries.

Background: The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk has been extensively explored, but their results are conflicting rather than conclusive. To clarify the precise effects of MTHFR polymorphisms on the risk of breast cancer, a systemic review and most comprehensive meta-analysis of all available studies relating MTHFR rs1801133 gene polymorphism to the risk of breast cancer was conducted., Methods: Eligible articles were identified by search of databases including Medline (Mainly PubMed), Embase, Web of Science, Chinese Biomedical Literature database (CBM), CNKI and Wanfang Medical databases. Crude ORs with 95% CIs were used to assess the strength of association., Results: Finally, a total of 83 studies with 35,029 cases and 38,990 controls were included. Overall, MTHFR rs1801133 gene polymorphism was proved to contribute to the risk of breast cancer under all genetic models (TT vs. CC: Pheterogeneity <0.001, OR=1.141, 95%CI=1.065-1.222, P <0.001; TT vs. CT: Pheterogeneity <0.001, OR=1.085, 95%CI=1.021-1.154, P=0.009; TT + CT vs. CC: Pheterogeneity <0.001, OR=1.040, 95%CI=1.020-1.061, P <0.001; TT vs. CC + CT: Pheterogeneity <0.001, OR=1.131, 95%CI=1.052-1.215, P=0.0478; T allele vs. C allele: Pheterogeneity <0.001, OR=1.040, 95%CI=1.009-1.071, P=0.010)., Conclusions: The results of this meta-analysis suggest that MTHFR rs1801133 gene polymorphism may the therapeutic target for breast cancer.