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We report an unconventional I 2 -catalyzed cascade reaction for the synthesis of angular triquinane derivatives with a fused heterocycle skeleton, leveraging enaminones and anilines as simple acyclic precursors. The key to success lies in I 2 functioning as a polar-reversal catalyst, which alters the reactivity at the α-position of the enaminone and facilitates the first hexa-functionalization of an enaminone along with the formation of highly congested continuous stereocenters.

Insect pheromones are critical chemical signals that regulate intraspecific behavior and play a key role in the dynamic monitoring and control of pest populations. Historically, research on insect pheromones has primarily focused on lipid-based compounds. However, terpenes and terpenoids, which are widely occurring classes of bioactive compounds, also play significant roles in insect pheromone blends. Over 50 terpene and terpenoid-based pheromones have been identified in over 52 insect species, spanning various orders such as Coleoptera, Hymenoptera, Blattodea, Hemiptera, Diptera, and Lepidoptera. These compounds are associated with several types of pheromones, including female or male sex pheromones, aggregation pheromones, alarm pheromones, and aphrodisiac pheromones. Terpenes and terpenoids may act as either primary or secondary components of pheromone blends and influence a wide range of critical insect behaviors. They play essential roles in the physiological and ecological adaptation of insects to their environment. This review provides a comprehensive overview of current research on terpene and terpenoid-based pheromones in insects, examining their structures, types, and physiological and ecological functions. Additionally, we propose future research directions to guide the application of these pheromones in insect behavioral regulation and pest management, while advocating for their broader use in insect pest monitoring and control., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. 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.)

Defluorinative cyclization of CF 3 -alkenes has emerged as a reliable strategy for crafting intricate polycyclic frameworks. In this study, a facile defluorinative bicyclization approach was developed for the construction of 4 H ,5 H -pyrano[3,2- c ]chromenes under mild conditions involving a sequence of intramolecular cyclization and intermolecular defluoroheterocyclization. A variety of polysubstituted 4 H ,5 H -pyrano[3,2- c ]chromenes featuring C2-fluorine could be synthesized in good yields with excellent tolerance toward various functional groups. Moreover, the introduction of a C-F bond provides additional possibilities for further modification of this skeleton. The product features aggregation-induced emission (AIE) characteristics after simple modification, which is promising for chemical and biomedical imaging.

A facile one-pot synthetic method has been developed for constructing 6- oxa -spiro[4.5]decane skeletons by merging the ring-opening of benzo[ c ]oxepines and formal 1,2-oxygen migration reactions. More than 30 examples of the 6- oxa -spiro[4.5]decane derivatives have been synthesized under transition-metal-free conditions.

A three-component annulation reaction and trifluoromethylation for the construction of 3-(trifluoromethyl)-4 H -pyrans using β-CF 3 -1,3-enynes, BrCF 2 CO 2 Et, and sulfoxonium ylides as readily available substrates has been developed. This metal-free process involves two C-F bond cleavages of β-CF 3 -1,3-enynes and a CF 3 group generated in situ from BrCF 2 CO 2 Et. This method is applicable to the late-stage modification of pharmaceutically active molecules.

Background: According to the population statistics in 2023, there were 110000 people aged over 100 years in China, and the experience of using Paxlovid (nirmatrelvir/ritonavir) for centenarians is particularly valuable. This article reports our experience of using Paxlovid in a centenarian with the novel coronavirus disease 2019 (COVID-19) infection., Case Summary: A 103-year-old female with mild COVID-19 and renal insufficiency was given sufficient Paxlovid for 2 days and a half dose for 3 days. During treatment, the patient was complicated with lung infection and heart failure, and nucleic acid remained positive. After expert consultation, a full dose of Paxlovid was given again on the 9th day of admission for 2 days and a half dose for 3 days. Meanwhile, anti-heart failure and antibiotics were administered; the heart failure and pulmonary infection were improved. Finally, on the 33 th day of admission, nucleic acid turned negative, body temperature returned to normal, cough and sputum, fatigue, poor appetite and other symptoms basically improved. The patient was given Paxlovid via nasal feeding for 2 courses without deterioration of liver and kidney function, diarrhea, nausea and vomiting, myalgia, chest tightness and other side effects, and was discharged from hospital with good recovery., Conclusion: This case suggests that Paxlovid can be used cautiously in centenarians with renal insufficiency and two courses of treatment can be considered in patients with persistent positive nucleic acid., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

A novel process using N -benzylhydroxylamine hydrochloride as a "C1N1 synthon" in [2+2+1] cyclization for the construction of 1,2,5-trisubstituted imidazoles has been described for the first time. The key to realizing this process lies in capturing arylamines by in situ generated novel acyl ketonitrone intermediates. Subsequent tautomerization activates the α-C(sp 3 )-H of N -benzylhydroxylamines, and thus breaks through its inherent reaction mode and achieves N , α-C site-selective cyclization. Furthermore, this method enables scale-up synthesis and late-stage modification of complex molecules.

The performance of biochar (BC) in reducing the transport of antibiotics under field conditions has not been sufficiently explored. In repacked sloping boxes of a calcareous soil, the effects of different BC treatments on the discharge of three relatively weakly sorbing antibiotics (sulfadiazine, sulfamethazine, and florfenicol) via runoff and drainage were monitored for three natural rain events. Surface application of 1 % BC (1 %BC-SA) led to the most effective reduction in runoff discharge of the two sulfonamide antibiotics, which can be partly ascribed to the enhanced water infiltration. The construction of 5 % BC amended permeable reactive wall (5 %BC-PRW) at the lower end of soil box was more effective than the 1 %BC-SA treatment in reducing the leaching of the most weakly sorbing antibiotic (florfenicol), which can be mainly ascribed to the much higher plant available and drainable water contents in the 5 %BC-PRW soil than in the unamended soil. The results of this study highlight the importance of BC's ability to regulate flow pattern by modifying soil hydraulic properties, which can make a significant contribution to the achieved reduction in the transport of antibiotics offsite or to groundwater., 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 B.V. All rights reserved.)

The phyllosphere is a vital yet often neglected habitat hosting diverse microorganisms with various functions. However, studies regarding how the composition and functions of the phyllosphere microbiome respond to agricultural practices, like nitrogen fertilization, are limited. This study investigated the effects of long-term nitrogen fertilization with different levels (CK, N90, N210, N330) on the functional genes and pathogens of the rice phyllosphere microbiome. Results showed that the relative abundance of many microbial functional genes in the rice phyllosphere was significantly affected by nitrogen fertilization, especially those involved in C fixation and denitrification genes. Different nitrogen fertilization levels have greater effects on fungal communities than bacteria communities in the rice phyllosphere, and network analysis and structural equation models further elucidate that fungal communities not only changed bacterial-fungal inter-kingdom interactions in the phyllosphere but also contributed to the variation of biogeochemical cycle potential. Besides, the moderate nitrogen fertilization level (N210) was associated with an enrichment of beneficial microbes in the phyllosphere, while also resulting in the lowest abundance of pathogenic fungi (1.14 %). In contrast, the highest abundance of pathogenic fungi (1.64 %) was observed in the highest nitrogen fertilization level (N330). This enrichment of pathogen due to high nitrogen level was also regulated by the fungal communities, as revealed through SEM analysis. Together, we demonstrated that the phyllosphere fungal communities were more sensitive to the nitrogen fertilization levels and played a crucial role in influencing phyllosphere functional profiles including element cycling potential and pathogen abundance. This study expands our knowledge regarding the role of phyllosphere fungal communities in modulating the element cycling and plant health in sustainable agriculture., 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. Published by Elsevier B.V.)

An unconventional [1 + 1 + 1 + 1 + 1 + 1] annulation process was developed for the construction of β,β-dithioketones by merging C-C and C-S bond cleavage. In this reaction, rongalite concurrently served as triple C1 units, dual sulfur(II) synthons, and a reductant for the first time. Mechanism investigation indicated that the reaction involved the self-mediated valence state change of rongalite. By performing this step-economical method, the challenging construction of C 5 -substituted 1,3-dithiane can be achieved under mild and simple conditions.

Though the evidence for antibiotic resistance spread via plant microbiome is mounting, studies regarding antibiotic resistome in the plant seed, a reproductive organ and important food resource, are still in their infancy. This study investigated the effects of long-term organic fertilization on seed bacterial endophytes, resistome, and their intergenerational transfer in the microcosm. A total of 99 antibiotic resistance genes (ARGs) and 26 mobile genetic elements (MGEs) were detected by high-throughput quantitative PCR. The amount of organic fertilizer applied was positively correlated to the number and relative abundance of seed-associated ARGs and MGEs. Moreover, the transmission of ARGs from the rhizosphere to the seed was mainly mediated by the shared bacteria and MGEs. Notably, the rhizosphere of progeny seedlings derived from seeds harboring abundant ARGs was found to have a higher relative abundance of ARGs. Using structural equation models, we further revealed that seed resistome and MGEs were key factors affecting the ARGs in the progeny rhizosphere, implying the seed was a potential resistome reservoir for rhizosphere soil. This study highlights the overlooked role of seed endophytes in the dissemination of resistome in the soil-plant continuum, and more attention should be paid to plant seeds as vectors of ARGs within the "One-Health" framework.

Herein, we disclose a straightforward approach to access transition-metal-free reductive N -formylation of nitroarenes. This reaction integrates the dual role of rongalite, which acts as a reductant and a C1 building block concurrently. This provides an alternative method for the synthesis of N -aryl formamides from nitroarenes, including the construction of a C-N bond. The utility of this protocol was demonstrated by scale-up synthesis and late-stage functionalizations of complex molecules.

Background: Large cell lung carcinoma (LCLC) is an exceptionally aggressive disease with a poor prognosis. At present, little is known about the molecular pathology of LCLC., Methods: Ultra-deep sequencing of cancer-related genes and exome sequencing were used to detect the LCLC mutational in 118 tumor-normal pairs. The cell function test was employed to confirm the potential carcinogenic mutation of PI3K pathway., Results: The mutation pattern is determined by the predominance of A > C mutations. Genes with a significant non-silent mutation frequency (FDR) < 0.05) include TP53 (47.5%), EGFR (13.6%) and PTEN (12.1%). Moreover, PI3K signaling (including EGFR, FGRG4, ITGA1, ITGA5, and ITGA2B) is the most mutated pathway, influencing 61.9% (73/118) of the LCLC samples. The cell function test confirmed that the potential carcinogenic mutation of PI3K pathway had a more malignant cell function phenotype. Multivariate analysis further revealed that patients with the PI3K signaling pathway mutations have a poor prognosis (P = 0.007)., Conclusions: These results initially identified frequent mutation of PI3K signaling pathways in LCLC and indicate potential targets for the treatment of this fatal type of LCLC., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

A concise and efficient hydrodefluorination process was developed for the synthesis of gem -difluoroalkenes. This reaction employs rongalite as a masked proton source and does not require any additional catalysts or reductants. Notably, trifluoromethyl alkenes having both terminal and internal double bonds are compatible with this process, allowing for a wider range of substrates. The successful late-stage functionalizations of pharmaceuticals and gram-scale syntheses were used to demonstrate the viability of this method.

Introduction: The mechanism of internet game addiction is unclear. Whether anxiety mediates between resourcefulness and internet game addiction and whether gender affect its mediation role have not been studied previously., Methods: A total of 4,889 college students from a college in southwest China were included in this study to complete the investigation, in which three questionnaires were used for evaluation., Results: Pearson's correlation analysis indicated a remarkable negative correlation between resourcefulness with internet game addiction and anxiety, as well as a significant positive correlation between anxiety and this addiction. The structural equation model confirmed the mediation role of anxiety. The multi-group analysis confirmed the moderating role of gender in the mediation model., Discussion: These findings have advanced the results of existing studies, indicating the buffering effect of resourcefulness on internet game addiction and revealing the potential mechanism of this relationship., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Zhong, Luo, He, Lin, Zauszniewski, Zhou, Chen, Wu, Wang, Li, Tang, Li, Wu and Luo.)

Heart failure (HF) is a complex clinical syndrome caused by various cardiovascular diseases. Its main pathogenesis includes cardiomyocyte loss, myocardial energy metabolism disorder, and activation of cardiac inflammation. Due to the clinically unsatisfactory treatment of heart failure, different mechanisms need to be explored to provide new targets for the treatment of this disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a gene mainly related to familial hypercholesterolemia, was discovered in 2003. Aside from regulating lipid metabolism, PCSK9 may be involved in other biological processes such as apoptosis, autophagy, pyroptosis, inflammation, and tumor immunity and related to diabetes and neurodegenerative diseases. Recently, clinical data have shown that the circulating PCSK9 level is significantly increased in patients with heart failure, and it is related to the prognosis for heart failure. Furthermore, in animal models and patients with myocardial infarction, PCSK9 in the infarct margin area was also found to be significantly increased, which further suggested that PCSK9 might be closely related to heart failure. However, the specific mechanism of how PCSK9 participates in heart failure remains to be further explored. The purpose of this review is to summarize the potential mechanism of PCSK9's involvement in heart failure, thereby providing a new treatment strategy for heart failure., Competing Interests: Conflict of interest statement The authors declare no conflict of interest, financial or otherwise., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

An unprecedented [1+1+1+1+1+1] annulation process has been developed for the construction of tetrahydro-2 H -thiopyran 1,1-dioxides. Notably, rongalite acted as a tethered C-S synthon in this reaction and can be chemoselectively used as triple C1 units and as a source of sulfone. Mechanistic investigation indicated that two different carbon-increasing models are involved in this reaction in which rongalite serves as C1 units.

Background: Polyarthritis is the most frequent clinical manifestation in antisynthetase syndrome (ASS) forms of idiopathic inflammatory myositis and may be misdiagnosed as rheumatoid arthritis (RA), particularly in patients with seronegative RA (SNRA). It is unclear whether there is an overlap between ASS and RA, or if ASS sometimes mimics RA. Pulmonary hypertension (PAH) is common in connective tissue diseases (CTDs). However, published reports on CTD-PAH do not include overlapping CTDs, and its incidence and impact on patient prognosis are unclear., Case Summary: We report the case of a 63-year-old woman who presented with a 3-mo history of symptom aggravation of recurrent symmetrical joint swelling and pain that had persisted for over 10 years. The patient was diagnosed with RA and interstitial lung disease. The patient repeatedly presented to the hospital's respiratory and rheumatology departments with arthralgia, plus shortness of breath after activity. Relevant tests indicated that anti-CCP and RF remained negative, while anti-J0-1 and anti-Ro-52 were strongly positive. It was not until recently that we recognized that this could be an unusual case of SNRA with concurrent ASS. Joint pain was relieved after regular anti-rheumatic treatment. Chest computed tomography scans showed that pulmonary interstitial changes did not progress significantly over several years; however, they showed gradual widening of the pulmonary artery, and cardiac ultrasound indicated elevated pulmonary artery systolic pressure. The prescribed treatment of PAH was not effective in improving shortness of breath., Conclusion: Overlap of RA and ASS may be missed. Further research is necessary to facilitate early diagnosis, effective evaluation, and prognosis., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Lung adenocarcinoma (LUAD) is one of the most prevalent forms of lung cancer. Competitive endogenous RNA (ceRNA) plays an important role in the pathogenesis of lung cancer. Phosphatase and tensin homolog (PTEN) is one of the most frequently deleted tumour suppressor genes in LUAD. The present study aimed to identify a novel PTEN-associated-ceRNA regulatory network and identify potential prognostic markers associated with LUAD. Transcriptome sequencing profiles of 533 patients with LUAD were obtained from TCGA database, and differentially expressed genes (DEGs) were screened in LUAD samples with PTEN high- (PTEN high ) and low- (PTEN low ) expression. Eventually, an important PTEN-related marker was identified, namely, the LINC00460/miR-150-3p axis. Furthermore, the predicted target genes (EME1/HNRNPAB/PLAUR/SEMA3A) were closely related to overall survival and prognosis. The LINC00460/miR-150-3p axis was identified as a clinical prognostic factor through Cox regression analysis. Methylation analyses suggested that abnormal regulation of the predicted target genes might be caused by hypomethylation. Furthermore, immune infiltration analysis showed that the LINC00460/miR-150-3p axis could alter the levels of immune infiltration in the tumour immune microenvironment, and promote the clinical progression of LUAD. To specifically induce PTEN deletion in the lungs, we constructed an STP mouse model (SFTPC-rtTA/tetO-cre/Pten flox/+ ). Quantitative PCR (qPCR) and immunohistochemical (IHC) analysis were used to detect predicted target genes. Therefore, we revealed that the PTEN-related LINC00460/miR-150-3p axis based on ceRNA mechanism plays an important role in the development of LUAD and provides a new direction and theoretical basis for its targeted therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xin, Shen, Jiang, Liu, Li, Hou, Wu, Jia, Wu, Fu, Ma and Jiang.)

Pd-catalyzed cascade hydroarylation and C-H germylation of nonterminal alkenes and aryl iodides enabled by hydroxyl assistance have been developed. The key step in this C-H germylation cascade is the formation of a highly reactive oxo-palladacycle intermediate, which markedly restrained the β-H elimination process. Mechanistically, control experiments indicated that the hydroxyl group played an important role in this process. This transformation shows excellent reactivity and selectivity for most substrates investigated.

In this paper, the authors report the fabrication of a sensitive deep ultraviolet (DUV) photodetector by using an individual GaSe nanobelt with a thickness of 52.1 nm, which presents the highest photoresponse at 265 nm illumination with a responsivity and photoconductive gain of about 663 A W -1 and 3103 at a 3 V bias, respectively, comparable to or even better than other reported devices based on conventional wide bandgap semiconductors. According to the simulation, this photoelectric property is associated with the wavelength-dependent absorption coefficient of the GaSe crystal, for which incident light with shorter wavelengths will be absorbed near the surface, while light with longer wavelengths will have a larger penetration depth, leading to a blueshift of the absorption edge with decreasing thickness. Further finite element method (FEM) simulation reveals that the relatively thin GaSe nanobelt exhibits an enhanced transversal standing wave pattern compared to its thicker counterpart at a wavelength of 265 nm, leading to an enhanced light-matter interaction and thereby more efficient photocurrent generation. The device can also function as an effective image sensor with acceptable spatial resolution. This work will shed light on the facile fabrication of a high-performance DUV photodetector from non-ultrawide bandgap semiconductors., (© 2022 Wiley-VCH GmbH.)

In this work, we report on the synthesis of InSe nanobelts through a catalyst-free chemical vapor deposition (CVD) growth approach. A remarkable blue shift of the peak photoresponse was observed when the thickness of the InSe nanobelt decreases from 562 to 165 nm. Silvaco Technology Computer Aided Design (TCAD) simulation reveals that such a shift in spectral response should be ascribed to the wavelength-dependent absorption coefficient of InSe, for which incident light with shorter wavelengths will be absorbed near the surface, while light with longer wavelengths will have a greater penetration depth, leading to a red shift of the absorption edge for thicker nanobelt devices. Considering the above theory, three kinds of photodetectors sensitive to blue (450 nm), green (530 nm), and red (660 nm) incident light were achieved by tailoring the thickness of the nanobelts, which can enable the spectral reconstruction of a purple "H" pattern, suggesting the potential application of 2D layered semiconductors in full-color imaging.

Objectives: No approved pharmacotherapies are available for patients with interstitial pneumonia with autoimmune features (IPAF). In the present work, we aimed to evaluate the efficacy and safety of pirfenidone for the treatment of IPAF., Methods: A retrospective cohort study consisting of patients who met diagnostic criteria for IPAF was performed after a multidisciplinary review, and the patients receiving pirfenidone were compared with those in the non-pirfenidone group. The baseline data and diagnostic characteristics of patients were assessed. Pulmonary function and prednisone dose were analysed by a mix-effects model., Results: A total of 184 patients, who met the diagnostic criteria of IPAF, were divided into two groups: pirfenidone group (n=81) and non-pirfenidone group (n=103). Patients in the pirfenidone group had a lower forced vital capacity (FVC%, p<0.001) and a lower diffusion capacity for carbon monoxide (DLCO%, p=0.003). The pirfenidone group exhibited a greater increase of FVC% at 6 (p=0.003), 12 (p=0.013), and 24 (p=0.003) months. After adjustment for sex, age, UIP pattern, baseline FVC% and DLCO%, patients in the pirfenidone group continued to show a greater improvement in FVC% (χ2(1)=4.59, p=0.032). Subgroup analysis identified superior therapeutic effects of pirfenidone in patients with dosage >600 mg/day (p=0.010) and medication course >12 months (p=0.007). Besides, the pirfenidone group had a lower prednisone dose than the non-pirfenidone group after 12 months of treatment (p=0.002). Moreover, 17 patients (19.32%) experienced side effects after taking pirfenidone, including one case of anaphylactic shock., Conclusions: Pirfenidone (600-1,800 mg/day) might help improve FVC, with an acceptable safety and tolerability profile in IPAF patients.

Primary lung cancer is one of the most common malignant tumors in China. Approximately 60% of lung cancer patients have distant metastasis at the initial diagnosis, so it is necessary to find new tumor markers for early diagnosis and individualized treatment. Tumor markers contribute to the early diagnosis of lung cancer and play important roles in early detection and treatment, as well as in precision medicine, efficacy monitoring, and prognosis prediction. The pathological diagnosis of lung cancer in small biopsy specimens determines whether there are tumor cells in the biopsy and tumor type. Because biopsy is traumatic and the compliance of patients with multiple biopsies is poor, liquid biopsy has become a hot research direction. Liquid biopsies are advantageous because they are nontraumatic, easy to obtain, reflect the overall state of the tumor, and allow for real-time monitoring. At present, liquid biopsies mainly include circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. This review introduces the research progress and clinical application prospect of liquid biopsy technology for lung cancer., (© 2022. The Author(s).)

Rongalite has been used in several challenging synthetic transformations with operationally simple and effective protocols. However, the employment of multiple characteristics of rongalite in synthetic chemistry is comparatively little known. Herein we report a separate-embedding type sulfonylmethylation of sulfoxonium ylides in which rongalite concurrently acted as a sulfone source, C1 synthon, radical initiator, and potential reducing reagent for the first time. Notably, this facile and easy-handling reaction does not require a catalyst or prefunctionalized sulfonylmethylation reagents.

Drug resistance is a key factor in the treatment failure of clinical non-small cell lung cancer (NSCLC) patients after adjuvant chemotherapy. Here, our results provide the first evidence that eukaryotic translation initiation factor 2b subunit delta (EIF2B4)-Stratifin (SFN) fusion and increased SFN expression are associated with chemotherapy tolerance and activation of the phosphatidylinositol 3 kinase/v-akt murine thymoma viral oncogene (PI3K/Akt) signaling pathway in NSCLC patients, suggesting that SFN might have potential prognostic value as a tumor biomarker for the prognosis of patients with NSCLC., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

We examined the effect of microRNA-320b (miR-320b) on tumor growth and angiogenesis in lung cancer and also determined its downstream molecular mechanisms. Lung cancer tissues and adjacent non-cancerous tissues were collected from 66 patients with lung cancer. miR-320b expression was experimentally determined to be expressed at low level in cancer tissues. The results of gain-of-function experiments suggested that miR-320b overexpression suppressed cancer cell invasion, tube formation, tumor volume and angiogenesis in xenografted nude mice. Hepatocyte nuclear factor 4 gamma (HNF4G) was identified as a target of miR-320b based on in silico analysis. Dual-luciferase reporter gene assays further identified the binding relationship between HNF4G and miR-320b. Lung cancer tissues exhibited increased expression of HNF4G and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Meanwhile, HNF4G knockdown suppressed IGF2BP2 expression, thereby repressing cancer cell invasion and tube formation. Furthermore, IGF2BP2 modified m6A to increase the expression of thymidine kinase 1 (TK1), thus promoting angiogenesis. In nude mice, restoration of TK1 reversed the suppressive effect of miR-320b overexpression on tumor growth rate and CD31 expression. In conclusion, miR-320b suppresses lung cancer growth and angiogenesis by inhibiting HNF4G, IGF2BP2 and TK1., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

We studied the application of a mobile terminal application program in endotracheal tube (ETT) cuff pressure measurement to improve the implementation rate of scientific ETT cuff pressure measurement and to ensure that the pressure falls within the recommended range. A pre-post controlled study lasting for 18 months was undertaken in a 40-bed general intensive care unit (GICU). This included a 6-month baseline period (baseline group) and a 6-month intervention period (intervention group). The mobile terminal application program was applied to monitor the cuff pressure of endotracheal intubation as an intervention measure during the intervention period. ETT pressure was the main outcome measure, while gender, age, causes for ICU admission, sedation score, duration of prior intubation, size of ETT, and number of VAP patients were secondary outcomes. ETT cuff pressure was monitored 742 times in both the baseline group and the intervention group. A total of 56.9% of the cuff pressure measurements in the baseline group were within the recommended range, while 78.4% of measurements in the intervention group were within the recommended range, reflecting a statistically significant difference (P < 0.05). The application of the mobile terminal application program used for ETT cuff pressure measurement could improve the percentage of ETT cuff pressure measurements falling within the recommended range.

Patterned growth of periodic perovskite film arrays is essential for application in sensing devices and integrated optoelectronic systems. Herein, we report on patterned growth of addressable perovskite photodetector arrays through an uncured polydimethylsiloxane (PDMS) oligomer-assisted solution-processed approach, in which a periodic hydrophilic/hydrophobic substrate replicating the predesigned patterns of the PDMS stamp was formed due to the migration of uncured siloxane oligomers in the PDMS stamp to the intimately contacted substrate. By using this technique, MAPbI 3 film photodetector arrays with neglectable pixel-to-pixel variation, a responsivity of 2.83 A W -1 , specific detectivity of 5.4 × 10 12 Jones, and fast response speed of 52.7/57.1 μs (response/recovery time) were achieved. An 8 × 8 addressable photodetector array was further fabricated, which functioned well as a real-time image sensor with reasonable spatial resolution. It is believed that the proposed strategy will find potential application in large-scale fabrication of other photodetector arrays, which might be potentially important for future integrated optoelectronic devices.

Lung cancer has high incidence and mortality rates, in which lung squamous cell carcinoma (LUSC) is a primary type of non-small cell lung carcinoma (NSCLC). The aim of our study was to discover long non-coding RNAs (lncRNAs) associated with diagnose and prognosis for LUSC. RNA sequencing data obtained from LUSC samples were extracted from The Cancer Genome Atlas database (TCGA). Two prognosis-associated lncRNAs (including SFTA1P and LINC00519) were selected from LUSC samples, and the expression levels were also verified to be associated abnormal in LUSC clinical samples. Our findings demonstrate that lncRNAs SFTA1P and LINC00519 exert important functions in human LUSC and may serve as new targets for LUSC diagnosis and therapy., Competing Interests: None., (AJTR Copyright © 2021.)

Purpose: Vitamin D deficiency has been linked to overt thyroid diseases. Data on the effects of vitamin D status on thyroid function in children are less examined. The goal of the present study was to explore the association between serum 25-hydroxyvitamin D [25(OH)D] levels and thyroid function parameters in early childhood., Patients and Methods: This was a cross-sectional study involving record-linkage of children's data of routine health check-ups for promoting early childhood development at Guangdong Women and Children's Hospital; 2869 children aged 6-24 months were included from January 2015 to May 2017. Serum 25(OH)D, thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels were measured using the electrochemiluminescence immunoassay., Results: The study population had a mean serum 25(OH)D level of 79.7 ± 28.1 nmol/L and 12.5% vitamin D deficiency and 36.0% insufficiency rates. The rates of thyroid dysfunctions detected were 2.9% hypothyroidism, 4.2% subclinical hypothyroidism, 0.9% hyperthyroidism, and 1.7% subclinical hyperthyroidism among the previously healthy children aged 6 to 24 months. Serum 25(OH)D levels had no significant correlation with TSH (r = 0.022, P = 0.236), FT3 (r = 0.014, P = 0.440) and FT4 (r = -0.059, P = 0.056) levels. No significant difference in the levels of thyroid hormones was found between the different quartiles of 25(OH)D level. Vitamin D deficiency [25(OH)D < 50 nmol/L] was associated with hypothyroidism (adjusted odds ratio = 2.16, 95% confidence interval: 1.18-3.94) but not with subclinical hypothyroidism, hyperthyroidism, and subclinical hyperthyroidism., Conclusion: Vitamin D deficiency is slightly associated with hypothyroidism. No associations were found between serum 25(OH)D levels and thyroid-related measures (TSH, FT3, and FT4) in previously healthy children aged 6-24 months., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Guo et al.)

Background: Brown adipose tissue (BAT) has been regarded as a potential target organ to combat obesity and related metabolic disorders. However, the effect of BAT activation on the development of diabetic kidney disease (DKD) remains unclear., Methods: Diabetic mice were induced by streptozotocin (STZ) combined with a high-fat diet. To activate BAT, mice were administered 1 mg/kg per day, i.p., CL316,243, a β 3 -adrenergic receptor agonist, for 4 weeks. Blood glucose, serum lipids, adipokines, 24-hour urinary albumin, 8-hydroxydeoxyguanosine (8-OHdG), and circulating microRNA (miRNA) levels were analyzed, in addition to renal pathology. Histological changes (fibrosis, inflammation) were evaluated in the kidneys, as was the expression of oxidative stress-related genes. Renal signaling pathways (fibroblast growth factor [Fgf]21/β-klotho/FGF receptor 1c and AMP-activated protein kinase[AMPK]/sirtuin 1 [Sirt1]/peroxisome proliferator-activated receptor-γ coactivator-1α [Pgc1α]) were also evaluated., Results: Compared with untreated STZ-diabetic mice, CL316,243 treatment reduced blood glucose, albeit not significantly (20.58 ± 3.55 vs 23.60 ± 3.90 mM), and significantly decreased triglycerides and low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol. Simultaneously, BAT activation significantly decreased 24-hour urinary albumin (34.21 ± 6.28 vs 70.46 ± 15.81 μg/24 h; P < 0.05) and 8-OHdG, improved renal fibrosis, inflammation, and oxidative stress, and ameliorated renal morphological abnormalities. In addition to enhancing BAT activity, CL316,243 significantly increased serum adiponectin concentrations and renal Fgf21 sensitivity, and reactivated the renal AMPK/Sirt1/Pgc1α signaling pathway. Furthermore, CL316,243 treatment increased levels of some circulating miRNAs and downregulated expression of their target genes in the kidney., Conclusions: Activating BAT could improve kidney injury in diabetic mice via metabolic improvements and renal AMPK activation by beneficial adipokines and miRNAs., (© 2019 The Authors. Journal of Diabetes published by John Wiley & Sons Australia, Ltd and Ruijin Hospital, Shanghai Jiaotong University School of Medicine.)

An efficient rhodium-catalyzed enantioselective arylation of isatin-derived N -Boc ketimines with arylboroxines has been developed using H 8 -BINOL-derived phosphite-olefin as a chiral ligand. This method allows access to a broad variety of valuable tetrasubstituted 3-amino-2-oxindole derivatives in good yields (up to 98%) with excellent enantioselectivities (up to 98% ee).

A rhodium/sulfur-olefin complex catalyzed asymmetric 1,2-addition of arylboronic acids to six-membered 1,2,6-thiadiazinane 1,1-dioxide-type cyclic imines to access highly optically active sulfamides (95-99% ee) has been developed. By taking advantage of the simple functional group transformations, an interesting array of valuable chiral 1,3-diamines with different substitution patterns can be readily obtained in a highly enantioenriched manner.

Fluorination is an effective process to open the band gap of graphene (Gr), which is beneficial to the development of optoelectronic devices working in wide wavelength. Herein, we report a dual-mode broadband photodetector (PD) by integrating fluorinated graphene (F-Gr) with silicon (Si). It is found that when working in photoconductive mode, the F-Gr/Si heterojunction exhibited a remarkable photoresponse over a wide spectral region from ultraviolet (UV), visible to near infrared (NIR) light with a high responsivity ( R) of 1.9 × 10 7 A W -1 and specific detectivity ( D*) of 4.4 × 10 12 Jones at 650 nm. Nonetheless, both parameters will be considerably reduced when the F-Gr/Si heterojunction works in the photodiode mode. In this mode, the I light / I dark ratio is as high as 2.0 × 10 5 and the response speed is accelerated by more than 3 orders of magnitude from about 5 ms to 6.3 μs. Notably, the responsivity of the device in the UV and NIR regions was remarkably enhanced in comparison with that of pristine Gr/Si-heterojunction-based devices. Considering the F-coverage-dependent band gap of the F-Gr revealed by the first-principle calculations, we believe that the enhancement was ascribed to the opening of the band gap in the partially fluorinated Gr, which is stabilized due to the configuration entropy as the temperature increases. The dual-mode PD enabled the simultaneous weak light detection and fast photodetection, which overcome the limitation of the traditional monomode PD.

We report the fabrication of KCu 7 S₄/Cu x O/Au devices with interfacial Cu x O layers of different thicknesses through the spontaneous oxidation of Cu film during deposition. Deposition was conducted with an electron-beam evaporation system under the deposition rate and the chamber pressure of 0.1 Å s -1 and 9.8×10 -3 Pa, respectively. X-ray diffraction and X-ray photoelectron spectroscopy characterizations reveal that the interfacial Cu x O layers mostly comprise Cu₂O and CuO. Electrical characterization reveals that the devices exhibit remarkably thickness-dependent resistive switching behavior. After undergoing an electroforming process under a high compliant current of 1000 μ A, the KCu 7 S₄/16 nm Cu x O/Au device exhibits stable bipolar resistive switching behavior with the set voltage of 0.58 V and reset voltage of -0.21 V, whereas the KCu 7 S₄/32 nm Cu x O/Au device only shows a hysteresis loop in the forward voltage regime. These findings are ascribed to the existence of high-insulation CuO, which is difficult to be softly broken down. Therefore, the depositional condition of Cu film and the thickness of the interfacial layer should be appropriately controlled for the effective performance of devices with Cu electrodes. The results may also provide guidance for the improvement of the performance and stability of Cu-based nonvolatile memory devices.

Controlled growth of high-quality patterned perovskite films on a large scale is essentially required for the application of this class of materials in functional integrated devices and systems. Herein, graphene-assisted hydrophilic-hydrophobic surface-induced growth of Cs-doped FAPbI 3 perovskite films with well-patterned shapes by a one-step spin-coating process is developed. Such a facile fabrication technique is compatible with a range of spin-coated perovskite materials, perovskite manufacturing processes, and substrates. By employing this growing method, controllable perovskite photodetector arrays are realized, which have not only prominent photoresponse properties with a responsivity and specific detectivity of 4.8 AW -1 and 4.2 × 10 12 Jones, respectively, but also relatively small pixel-to-pixel variation. Moreover, the photodetectors array can function as an effective visible light image sensor with a decent spatial resolution. Holding the above merits, the proposed technique provides a convenient and effective pathway for large-scale preparation of patterned perovskite films for multifunctional application purposes., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Herein, we demonstrate the use of heterostructures comprised of Co/β-Mo 2 C@N-CNT hybrids for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in an alkaline electrolyte. The Co can not only create a well-defined heterointerface with β-Mo 2 C but also overcomes the poor OER activity of β-Mo 2 C, thus leading to enhanced electrocatalytic activity for HER and OER. DFT calculations further proved that cooperation between the N-CNTs, Co, and β-Mo 2 C results in lower energy barriers of intermediates and thus greatly enhances the HER and OER performance. This study not only provides a simple strategy for the construction of heterostructures with nonprecious metals, but also provides in-depth insight into the HER and OER mechanism in alkaline solution., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The generation of transgenic chickens is of both biomedical and agricultural significance, and recently chicken transgenesis technology has been greatly advanced. However, major issues still exist in the efficient production of transgenic chickens. This study was designed to optimize the production of enhanced green fluorescence protein (EGFP)-transgenic broilers, including egg windowing at the blunt end (air cell) of egg, and the direct transfection of circulating primordial germ cells by microinjection of the Tol2 plasmid-liposome complex into the early embryonic dorsal aorta. For egg windowing, we discovered that proper manipulation of the inner shell membrane at the blunt end could improve the rate of producing G0 transgenic roosters. From 27 G0 roosters, we successfully collected semen with EGFP-positive sperms from 16 and 19 roosters after direct fluorescence observation and fluorescence-activated cell sorting analyses (13 detected by both methods), respectively. After artificial insemination using the G0 rooster with the highest number of EGFP fluorescent sperm, one G1 EGFP transgenic broiler (1/81, 1.23%) was generated. Our results indicate that appropriate egg windowing and screening of potentially transgene-positive roosters can improve the production of germline-transmitted transgenic birds.

High-performance photodetectors are desirable for various applications, including multi-wavelength image sensing, communication, and safety monitoring. In this study, we report the construction of a dual-surface plasmon-enhanced silicon Schottky photodetector using Au nanoparticles (NPs)/graphene/Au NPs hybrid structure as the electrode. It was found that the as-assembled device exhibited broad sensitivity, ranging from ultraviolet to near-infrared light (360-1330 nm) at room temperature, with a high response speed of 360 ns and a 3 dB bandwidth of 780 kHz at zero bias. Further theoretical simulation based on the finite-element method revealed that good device performance is associated with the contribution of the Au NPs/graphene/Au NPs electrode: intense dual-plasmonic resonance coupling is induced in a hybrid structure of two layers of metallic NPs separated by a uniform monolayer graphene. It not only can enhance light trapping and the localized electric field at the resonant and off-resonant wavelength regions, but is also beneficial for the tunneling of hot electrons. This work demonstrated the great potential of dual-plasmonic resonance coupling in optoelectronic devices and will lead to the development of advanced plasmonic devices.

Increasing evidence indicates that tumor-initiating cells (TICs) are responsible for the occurrence, development, recurrence, and development of the drug resistance of cancer. MicroRNA (miRNA) plays a significant functional role by directly regulating targets of TIC-triggered non-small-cell lung cancer (NSCLC), but little is known about the function of the miR-30 family in TICs. In this study, we found the miR-30 family to be downregulated during the spheroid formation of NSCLC cells, and patients with lower miR-30a/c expression had shorter overall survival (OS) and progression-free survival (PFS). Moreover, transmembrane 4 super family member 1 (TM4SF1) was confirmed to be a direct target of miR-30a/c. Concomitant low expression of miR-30a/c and high expression of TM4SF1 correlated with a shorter median OS and PFS in NSCLC patients. miR-30a/c significantly inhibited stem-like characteristics in vitro and in vivo via suppression of its target gene TM4SF1, and then it inhibited the activity of the mTOR/AKT-signaling pathway. Thus, our data provide the first evidence that TM4SF1 is a direct target of miR-30a/c and miR-30a/c inhibits the stemness and proliferation of NSCLC cells by targeting TM4SF1, suggesting that miR-30a/c and TM4SF1 may be useful as tumor biomarkers for the diagnosis and treatment of NSCLC patients., (Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

To investigate the expression level of microRNA-101-3p (miR-101-3p) and its possible association with progression, prognosis and chemotherapy in patients with non-small cell lung cancer (NSCLC), the Gene Expression Omnibus (GEO) database was used. Quantitative polymerase chain reaction was used to verify the expression in 327 NSCLC and 42 adjacent normal lung tissues, of which 42 viable tissues were paired with nearby normal lung tissues. Based on the Cox regression model, univariate and multivariate analyses were used to address the factors that had effects on overall survival (OS) and disease-free survival (DFS) rate. Data from the GEO database demonstrated that the miR-101-3p expression in NSCLC was downregulated, compared with normal lung cancer. Survival analysis through univariate and multivariate models indicated that the miR-101-3p expression level was a crucial risk factor for OS and DFS in patients with NSCLC. A number of clinical parameters were determined to be associated with miR-101-3p expression, including tumor diameter, lymph node metastasis and tumor-node-metastasis stage. Adjuvant chemotherapy with high expression of miR-101-3p was determined to increase OS and DFS in patients with NSCLC, compared with patients with de novo or low expression of miR-101-3p. The present results demonstrated that miR-101-3p expression levels were associated with NSCLC progression and prognosis, which indicated that miR-101-3p may serve as a biomarker for patients with NSCLC who have received adjuvant chemotherapy.

Near infrared light (NIR) photodetectors based on one-dimensional semiconductor nanowires have generated considerable interest due to their practical application in versatile fields. We present a facile yet efficient approach to rationally integrating KCu 7 S 4 semiconductor nanowires by the Langmuir-Blodgett (LB) technique. A self-powered near infrared (NIR) light photodetector is fabricated by transferring a close-packed KCu 7 S 4 nanowire monolayer to the surface of a silicon wafer. The as-fabricated Si/KCu 7 S 4 heterojunction with a close-packed and well-aligned nanowire array exhibits splendid photovoltaic performance when illuminated by NIR light, allowing the detection of NIR light without an exterior power supply. The photodetector exhibits a high sensitivity to NIR light (980 nm, 295.3 μW cm -2 ) with responsivity (R) 15 mA W -1 and detectivity (D*) 2.15 × 10 12 cm Hz 1/2 W -1 . Significantly, the device shows the capability to work under high pulsed light irradiation up to 50 kHz with a high-speed response (response time τ r 7.4 μs and recovery time τ f 8.6 μs). This facilitates the fabrication of low-cost and high-speed photodetectors and integrated optoelectronic sensor circuitry.

Biomimetic assembly of high-quality nanosheets into nacre-like structures can produce macroscopic films with favorable mechanical and optical performances due to the intrinsic properties and high level of ordering of the nanoscale building blocks. Natural ground mica is abundant and exhibits great application potential. However, large size and low aspect ratio greatly limit its biomimetic assembly. Moreover, exfoliation of ground mica into high-quality nanosheets remains a significant challenge. Here, we report that large-scale exfoliation of ground mica into mono- or few-layered mica nanosheets with a production rate of ~1.0 g h - 1 can be successfully achieved. The mica nanosheets are then assembled into strong biomimetic polymeric mica film that inherits the high electric insulation, excellent visible transmittance, and unique ultraviolet-shielding properties of natural mica. Its overall performance is superior to that of natural sheet mica and other biomimetic films, making the polymeric mica film a suitable substrate for flexible and transparent devices.

Increasing evidence has shown that microRNAs (miRNAs) play a significant functional role by directly regulating respective targets in cancer stem cell (CSC)-induced non-small cell lung cancer (NSCLC) progression and resistance to therapy. In this study, we found that hsa-miR-124a was downregulated during spheroid formation of the NSCLC cell lines SPC-A1 and NCI-H1650 and NSCLC tissues compared with normal lung cells and tissues. Patients with lower hsa-miR-124a expression had shorter overall survival (OS) and progression free survival (PFS). Moreover, ubiquitin-specific protease 14 (USP14) was confirmed to be a direct target of hsa-miR-124a. Furthermore, concomitant low hsa-miR-124a expression and high USP14 expression were correlated with a shorter median OS and PFS in NSCLC patients. Cellular functional analysis verified that the tumor suppressor hsa-miR-124a negatively regulated cell growth and self-renewal, and promoted apoptosis and gefitinib sensitivity of lung cancer stem cells by suppressing its target gene USP14. Our results provide the first evidence that USP14 is a direct target of hsa-miR-124a, and that hsa-miR-124a inhibits stemness and enhances the gefitinib sensitivity of NSCLC cells by targeting USP14. Thus, hsa-miR-124a and USP14 may be useful as tumor biomarkers for the diagnosis and treatment of NSCLC., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: In avian species, liver is the main site of de novo lipogenesis, and hepatic lipid metabolism relates closely to adipose fat deposition. Using our fat and lean chicken lines of striking differences in abdominal fat content, post-hatch lipid metabolism in both liver and adipose tissues has been studied extensively. However, whether molecular discrepancy for hepatic lipid metabolism exists in chicken embryos remains obscure., Results: We performed transcriptome and proteome profiling on chicken livers at five embryonic stages (E7, E12, E14, E17 and E21) between the fat and lean chicken lines. At each stage, 521, 141, 882, 979 and 169 differentially expressed genes were found by the digital gene expression, respectively, which were significantly enriched in the metabolic, PPAR signaling and fatty acid metabolism pathways. Quantitative proteomics analysis found 20 differentially expressed proteins related to lipid metabolism, PPAR signaling, fat digestion and absorption, and oxidative phosphorylation pathways. Combined analysis showed that genes and proteins related to lipid transport (intestinal fatty acid-binding protein, nucleoside diphosphate kinase, and apolipoprotein A-I), lipid clearance (heat shock protein beta-1) and energy metabolism (NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 and succinate dehydrogenase flavoprotein subunit) were significantly differentially expressed between the two lines., Conclusions: For hepatic lipid metabolism at embryonic stages, molecular differences related to lipid transport, lipid clearance and energy metabolism exist between the fat and lean chicken lines, which might contribute to the striking differences of abdominal fat deposition at post-hatch stages.

Objective: To investigate the protective effect of exendin-4 against diabetic cardiomyopathy in mice and explore the underlying mechanism., Methods: C57BL/6J mice were randomly divided into normal control group with normal diet and diabetic group with high-fat diet for 4 weeks before streptozotocin injection. The successfully established diabetic mouse models were divided into diabetic group with exendin-4 treatment and diabetic control group for daily treatment with intraperitoneal injection of 1 nmol/kg exendin-4 and saline of equivalent volume for 8 weeks, respectively. The physiological parameters such as blood glucose and body weight were recorded. RT-PCR was used to examine the transcription levels of genes related with myocardial hypertrophy and fibrosis and the genes related with mitochondrial functions including PGC1α, NRF and CytoC. The expressions of oxidative stress markers and Sirt1/PGC1 proteins were measured using Western blotting. and HE staining was used to observe the myocardial structural changes in the mice., Results: Compared with the normal control mice, the mice in diabetic control group showed significantly increased blood glucose and blood lipid levels (P<0.001), which were obviously improved by Exendin-4 treatment. The expressions of ANP, BNP, TGFβ1, CytoC1 and NOX1 were significantly increased (P<0.05) while Sirt1, PGC1α, NRF and SOD1 expression were markedly decreased in the myocardial tissue of the diabetic mice (P<0.05). Exendin-4 treatment resulted in obviously reduced expressions of ANP, BNP, TGFβ1, CytoC1 and NOX1 (P<0.05) and increased expressions of Sirt1, PGC1α, NRF and SOD1 (P<0.05) in the diabetic mice., Conclusions: Exendin-4 protects against myocardial injury in diabetic mice by improving mitochondrial function and inhibiting oxidative stress through the Sirt1/PGC1α signaling pathway.

A site-selective rhodium-catalyzed asymmetric 1,4-/1,2-addition of arylboronic acids to challenging α,β-unsaturated cyclic ketimines was realized through a ligand-controlled strategy. By employing different chiral olefin ligands, a ligand-controlled switch in the reaction regioselectivity was attained for the first time. The reactions allow the synthesis of highly valuable α,α-disubstituted chiral allylic amines and enantioenriched 1,4-adducts. Further product transformation provided easy access to various quaternary carbon-containing chiral amines and amino acid derivatives bearing multifunctional groups.

Objective: To investigate the prevalence, etiology and clinical characteristics of adrenal lesions detected by abdominal computed tomography (CT)., Methods: This retrospective study was conducted in patients with adrenal lesions detected by abdominal CT examinations in Nanfang Hospital between July, 2014 and June, 2015. The clinical data of the patients were collected for analysis of the demographics, comorbidities, imaging characteristics, biochemical profiles, clinical diagnosis and intervention., Results: A total of 939 patients with adrenal lesions were identified from 19 004 patients undergoing abdominal CT scan over the defined period. The mean age of the patients was 53.2 years and 560 of the patients were male. Among the total cases with adrenal lesions, the percentages of cases with adrenal masses tended to increase progressively with age. Endocrine studies were done in 270 of the total patients, which identified non-functioning masses in 38.9%, primary aldosteronism in 16.3%, Cushing's syndrome in 4.1%, subclinical Cushing's syndrome in 7.0%, and pheochromocytomas in 7.0% of the cases. Adrenal incidentalomas was detected in 191 patients, with a detection rate of 1.0% among the overall patients undergoing abdominal CT scans. Imaging study detected adenomas (70.3%), cortical carcinomas (2.4%), and metastases (0.5%). Of 191 patients with adrenal incidentalomas, only 76 (39.8%) underwent endocrine evaluation, including 34 with nonfunctioning adrenal masses, 17 with pheochromocytoma, 7 with primary aldosteronism, and 5 with subclinical Cushing's syndrome., Conclusion: s The overall detection rates of adrenal lesions and adrenal incidentalomas by abdominal CT were 4.9% and 1.0%, respectively, in our cohort of patients undergoing the examination over the defined period. Although most of the lesions were benign and nonfunctioning, malignant and functional lesions were also detected. As many as 60% of the patients with adrenal incidentalomas did not have hormonal testing. Clinicians need to have greater awareness of adrenal incidentalomas and standard protocol for its management should be established.

Proprotein convertase subtilisin/kexin type 9 (PCSK9), also known as neural apoptosis regulated convertase (NARC1), is a key modulator of cholesterol metabolism. PCSK9 increases the serum concentration of low-density lipoprotein cholesterol by escorting low-density lipoprotein receptors (LDLRs) from the membrane of hepatic cells into lysosomes, where the LDLRs are degraded. Owing to the importance of PCSK9 in lipid metabolism, considerable effort has been made over the past decade in developing drugs targeting PCSK9 to lower serum lipid levels. Nevertheless, some problems and challenges remain. In this review we first describes the structure and function of PCSK9 and its gene polymorphisms. We then discuss the various designs of pharmacological targets of PCSK9, including those that block the binding of PCSK9 to hepatic LDLRs (mimetic peptides, adnectins, and monoclonal antibodies), inhibit PCSK9 expression (the clustered regularly interspaced short palindromic repeats/Cas9 platform, small molecules, antisense oligonucleotides, and small interfering RNAs), and interfere with PCSK9 secretion. Finally, this review highlights future challenges in this field, including safety concerns associated with PCSK9 monoclonal antibodies, the limited utility of PCSK9 inhibitors in the central nervous system, and the cost-effectiveness of PCSK9 inhibitors.