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Hong-Xia Duan, Xiu-Mei Wang, Yue Guo, Ling Wei, Rui-Xia Hao, Zhen-Shan Guo Department of Surgery, Shanxi Bethune Hospital (Shanxi Academy of Medical Sciences), Taiyuan, Shanxi, People’s Republic of ChinaCorrespondence: Hong-Xia Duan, Department of Surgery, Shanxi Bethune Hospital (Shanxi Academy of Medical Sciences), No. 99 Longcheng Street, Taiyuan, Shanxi, People’s Republic of China, Tel +86-3518379228, Email Duan_hongxia@yeah.netObjective: To investigate the application of a multidisciplinary collaboration model to optimise the configuration management of orthopaedic external device sets in general hospitals.Methods: A pretest–post-test study design was used. Sixty patients who underwent unilateral total knee arthroplasty and 60 patients who underwent posterior lumbar interbody fusion between March and May 2022 were recruited as the control stage. Additionally, a total of 120 patients, 60 of each, who underwent the two procedures between September and November 2022, were recruited as the experimental stage. For the control stage, conventional external equipment management was used, and for the experimental stage, an external device management programme was implemented based on multidisciplinary collaboration with the control stage. Based on the PDSA cycle, the configuration management of orthopaedic external device sets was optimised, and the differences in collating and counting external devices, nurses’ overtime in the external device stage and orthopaedic surgeon satisfaction were compared between the two stages.Results: Compared with the control stage, the collation count took less time (8.65 ± 0.25 min vs 5.37 ± 0.13 min; 13.55 ± 1.10 min vs 7.85 ± 0.82 min), the number of overtime hours was shorter (175.80 ± 12.19 min vs 96.68 ± 13.66 min) and orthopaedic surgeon satisfaction was improved (4.58 ± 0.62 vs 4.10 ± 0.68; 4.33 ± 0.73 vs 3.87 ± 0.77; 4.20 ± 0.71 vs 3.82 ± 0.71; 4.12 ± 0.69 vs 3.87 ± 0.72; 4.05 ± 0.68 vs 3.79 ± 0.68) in the experimental stage (all P < 0.05).Conclusion: Multidisciplinary collaboration offers various benefits for optimising the configuration of external device sets, such as reducing the time taken for the preoperative sorting and counting of external devices, enhancing nurses’ work efficiency and improving surgeons’ job satisfaction; therefore, it is worthy of reference in clinical practice.Keywords: operating theatre, optimisation configuration, external instruments, item counting, scientific management, work efficiency

Xin Xin, Wei Liu, Zhe-Ao Zhang, Ying Han, Ling-Ling Qi, Ying-Ying Zhang, Xin-Tong Zhang, Hong-Xia Duan, Li-Qing Chen, Ming-Ji Jin, Qi-Ming Wang, Zhong-Gao Gao, Wei Huang State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People’s Republic of ChinaCorrespondence: Zhong-Gao Gao; Wei HuangState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing, 100050, People’s Republic of ChinaTel +86-10-63026505Email zggao@imm.ac.cn; huangwei@imm.ac.cnBackground: Glioma is the most common primary malignant brain tumor with a dreadful overall survival and high mortality. One of the most difficult challenges in clinical treatment is that most drugs hardly pass through the blood–brain barrier (BBB) and achieve efficient accumulation at tumor sites. Thus, to circumvent this hurdle, developing an effectively traversing BBB drug delivery nanovehicle is of significant clinical importance. Rabies virus glycoprotein (RVG) is a derivative peptide that can specifically bind to nicotinic acetylcholine receptor (nAChR) widely overexpressed on BBB and glioma cells for the invasion of rabies virus into the brain. Inspired by this, RVG has been demonstrated to potentiate drugs across the BBB, promote the permeability, and further enhance drug tumor-specific selectivity and penetration.Methods: Here, we used the RVG15, rescreened from the well-known RVG29, to develop a brain-targeted liposome (RVG15-Lipo) for enhanced BBB permeability and tumor-specific delivery of paclitaxel (PTX). The paclitaxel-cholesterol complex (PTX-CHO) was prepared and then actively loaded into liposomes to acquire high entrapment efficiency (EE) and fine stability. Meanwhile, physicochemical properties, in vitro and in vivo delivery efficiency and therapeutic effect were investigated thoroughly.Results: The particle size and zeta potential of PTX-CHO-RVG15-Lipo were 128.15 ± 1.63 nm and − 15.55 ± 0.78 mV, respectively. Compared with free PTX, PTX-CHO-RVG15-Lipo exhibited excellent targeting efficiency and safety in HBMEC and C6 cells, and better transport efficiency across the BBB in vitro model. Furthermore, PTX-CHO-RVG15-Lipo could noticeably improve the accumulation of PTX in the brain, and then promote the chemotherapeutic drugs penetration in C6luc orthotopic glioma based on in vivo imaging assays. The in vivo antitumor results indicated that PTX-CHO-RVG15-Lipo significantly inhibited glioma growth and metabasis, therefore improved survival rate of tumor-bearing mice with little adverse effect.Conclusion: Our study demonstrated that the RVG15 was a promising brain-targeted specific ligands owing to the superior BBB penetration and tumor targeting ability. Based on the outstanding therapeutic effect both in vitro and in vivo, PTX-CHO-RVG15-Lipo was proved to be a potential delivery system for PTX to treat glioma in clinic.Keywords: glioma, blood–brain barrier, RVG15, liposome, paclitaxel

Qing Zhang,1 Hu-Xinyue Duan,1 Ruo-Lan Li,1 Jia-Yi Sun,2 Jia Liu,1 Wei Peng,1 Chun-Jie Wu,1 Yong-Xiang Gao3 1School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, People’s Republic of China; 2Innovation Research Institute, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, People’s Republic of China; 3School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, People’s Republic of ChinaCorrespondence: Chun-Jie WuSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, People’s Republic of ChinaTel +86-28-61801001Email wucjcdtcm@163.comYong-Xiang GaoSchool of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, People’s Republic of ChinaTel +86-28-61801001Email gaoyxcdtcm@126.comBackground and Objectives: Guizhi-Shaoyao-Zhimu decoction (GSZD) is often applied to control rheumatoid arthritis (RA), gout, osteoarthritis, etc. In this study, bioinformatic analysis and experimental verification were used to uncover the integral mechanism profile of GSZD against RA.Materials and Methods: The chemical compositions of GSZD were identified by UPLC-QTOF-MS/MS. MH7A cell model was established to screen active compounds in GSZD, and potential targets of these compounds were predicted through online database retrieval. The differential expression genes (DEGs) in synovial tissue of RA patients and normal controls were retrieved from the GEO database. DEGs and the predicated compounds targets were overlapped, and the overlapped genes were subsequently enriched by GO and KEGG analysis. The pathways with significant enrichments were further experimentally verified.Results: A total of 19 constituents were identified from GSZD, and 11 compounds showed obviously antiproliferative effects on MH7A cells with IC50 < 100 μg/mL. Bioinformatic analysis indicated that IL-1β, IL-6, MAPK8, JAK2, CXCL8, and CASP3 were the main targets of GSZD, and the integral pharmacological mechanisms profile of GSZD might be related to anti-inflammation and proapoptosis. GSZD can promote the loss of mitochondrial membrane potential (MOMP) and induce apoptosis in MH7A cells. Furthermore, in vitro experiments showed GSZD can not only downregulate mRNA expressions of IL-1β (p< 0.05), IL-6 (p< 0.05), MMPs (p< 0.05) and CCL5 (p< 0.05) but also inhibit the nuclear transcription of NF-κB. GSZD also reduced the expressions of Bcl-2 (p< 0.05), JAK2 (p< 0.05), STAT-3 (p< 0.05), whereas increase Bax (p< 0.05), Caspase-3 (p< 0.05) and caspase-9 (p< 0.05).Conclusion: Collectively, inducing synovial fibroblast apoptosis and inhibiting inflammatory response are two important ways for GSZD to RA, and our study proved bioinformatic analysis combined with experimental verification is a feasible method to explore the drug targets and mechanism of actions of TCMs.Keywords: apoptosis, anti-inflammatory, bioinformatic analysis, rheumatoid arthritis, Guizhi-Shaoyao-Zhimu decoction

Ruo-Lan Li,1 Li-Ying He,1 Qing Zhang,1 Jia Liu,1 Feng Lu,1 Hu-Xin-Yue Duan,1 Lin-Hong Fan,1 Wei Peng,1 Yong-Liang Huang,2 Chun-Jie Wu1 1School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, People’s Republic of China; 2Pharmacy Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, People’s Republic of ChinaCorrespondence: Yong-Liang Huang; Chun-Jie Wu Tel +86-28-6180-1001Email ld10000@126.com; wucjcdtcm@163.comAbstract: HIF-1α is an important factor regulating oxygen balance in mammals, and its expression is closely related to various physiological and pathological conditions of the body. Because HIF-1α plays an important role in the occurrence and development of cancer and other diseases, it has become an enduring research hotspot. At the same time, natural medicines and traditional Chinese medicine compounds have amazing curative effects in various diseases related to HIF-1 subtype due to their unique pharmacological effects and more effective ingredients. Therefore, in this article, we first outline the structure of HIF-1α and the regulation related to its expression, then introduce various diseases closely related to HIF-1α, and finally focus on the regulation of natural medicines and compound Chinese medicines through various pathways. This will help us understand HIF-1α systematically, and use HIF-1α as a target to discover more natural medicines and traditional Chinese medicines that can treat related diseases.Keywords: HIF-1α, disease, natural medicine, traditional Chinese medicine

Germinal matrix-intraventricular hemorrhage (GM-IVH) is a detrimental neurological complication that occurs in preterm infants, especially in babies born before 32 weeks of gestation and in those with a very low birth weight. GM-IVH is defined as a rupture of the immature and fragile capillaries located in the subependymal germinal matrix zone of the preterm infant brain, and it can lead to detrimental neurological sequelae such as posthemorrhagic hydrocephalus (PHH), cerebral palsy, and other cognitive impairments. PHH following GM-IVH is difficult to treat in the clinic, and no levelone strategies have been recommended to pediatric neurosurgeons. Several cellular and molecular mechanisms of PHH following GM-IVH have been studied in animal models, but no effective pharmacological strategies have been used in the clinic. Thus, a comprehensive understanding of molecular mechanisms, potential pharmacological strategies, and surgical management of PHH is urgently needed. The present review presents a synopsis of the pathogenesis, diagnosis, and cellular and molecular mechanisms of PHH following GM-IVH and explores pharmacological strategies and surgical management., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Physio-biochemical regulations governing crop growth period are pivotal for drought adaptation. Yet, the extent to which functionality of arbuscular mycorrhizal fungi (AM fungi) varies across different stages of maize growth under drought conditions remains uncertain. Therefore, periodic functionality of two different AM fungi i.e., Rhizophagus irregularis SUN16 and Glomus monosporum WUM11 were assessed at jointing, silking, and pre-harvest stages of maize subjected to different soil moisture gradients i.e., well-watered (80% SMC (soil moisture contents)), moderate drought (60% SMC), and severe drought (40% SMC). The study found that AM fungi significantly (p < 0.05) affected various morpho-physiological and biochemical parameters at different growth stages of maize under drought. As the plants matured, AM fungi enhanced root colonization, glomalin contents, and microbial biomass, leading to increased nutrient uptake and antioxidant activity. This boosted AM fungal activity ultimately improved photosynthetic efficiency, evident in increased photosynthetic pigments and photosynthesis. Notably, R. irregularis and G. monosporum improved water use efficiency and mycorrhizal dependency at critical growth stages like silking and pre-harvest, indicating their potential for drought resilience to stabilize yield. The principal component analysis highlighted distinct plant responses to drought across growth stages and AM fungi, emphasizing the importance of early-stage sensitivity. These findings underscore the potential of incorporating AM fungi into agricultural management practices to enhance physiological and biochemical responses, ultimately improving drought tolerance and yield in dryland maize cultivation., 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 Masson SAS. All rights reserved.)

Non-hydraulic root source signaling (nHRS) is a unique positive response to soil drying in the regulation of plant growth and development. However, it is unclear how the nHRS mediates the tradeoff between source and sink at the late growth stages and its adaptive mechanisms in primitive wheat. To address this issue, a root-splitting design was made by inserting solid partition in the middle of the pot culture to induce the occurrence of nHRS using four wheat cultivars (MO1 and MO4, diploid; DM22 and DM31, tetraploid) as materials. Three water treatments were designed as 1) both halves watered (CK), 2) holistic root system watered then droughted (FS), 3) one-half of the root system watered and half droughted (PS). FS and PS were designed to compare the role of the full root system and split root system to induce nHRS. Leaves samples were collected during booting and anthesis to compare the role of nHRS at both growth stages. The data indicated that under PS treatment, ABA concentration was significantly higher than FS and CK, demonstrating the induction of nHRS in split root design and nHRS decreased cytokinin (ZR) levels, particularly in the PS treatment. Soluble sugar and proline accumulation were higher in the anthesis stage as compared to the booting stage. POD activity was higher at anthesis, while CAT was higher at the booting stage. Increased ABA (nHRS) correlated with source-sink relationships and metabolic rate (i.e., leaf) connecting other stress signals. Biomass density showed superior resource acquisition and utilization capabilities in both FS and PS treatment as compared to CK in all plants. Our findings indicate that nHRS-induced alterations in phytohormones and their effect on source-sink relations were allied with the growth stages in primitive wheat., (© 2024. The Author(s).)

Macrophages are phenotypically and functionally diverse in the tumor microenvironment (TME). However, how to remodel macrophages with a protumor phenotype and how to manipulate them for therapeutic purposes remain to be explored. Here, we show that in the TME, RARγ is downregulated in macrophages, and its expression correlates with poor prognosis in patients with colorectal cancer (CRC). In macrophages, RARγ interacts with tumor necrosis factor receptor-associated factor 6 (TRAF6), which prevents TRAF6 oligomerization and autoubiquitination, leading to inhibition of nuclear factor κB signaling. However, tumor-derived lactate fuels H3K18 lactylation to prohibit RARγ gene transcription in macrophages, consequently enhancing interleukin-6 (IL-6) levels in the TME and endowing macrophages with tumor-promoting functions via activation of signal transducer and activator of transcription 3 (STAT3) signaling in CRC cells. We identified that nordihydroguaiaretic acid (NDGA) exerts effective antitumor action by directly binding to RARγ to inhibit TRAF6-IL-6-STAT3 signaling. This study unravels lactate-driven macrophage function remodeling by inhibition of RARγ expression and highlights NDGA as a candidate compound for treating CRC., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

It is crucial to clarify the physiological responses of wheat (T. aestivum) plants to source-sink manipulation and assimilation transportation under drought stress during domestication of dryland wheat. In this research, a two-year field experiment was conducted using nine wheat cultivars in a semiarid site of northwest China. The source-sink manipulation treatments including defoliation of flag leaves and 50% removal of ears were applied at the anthesis stage under two levels of drought stress conditions i.e. progressive water supply (PWS) and rainfed drought treatment (RDT). Our results indicated that drought stress reduced the dry weight of leaves, sheaths and stems, as well as caused a significant yield reduction. High ploidy wheat exhibits a greater capacity to sustain higher grain yields when subjected to drought stress, primarily due to its stronger buffer capacity between source supply and sink demand. All wheat species with different ploidy levels had a certain degree of source limitation and sink restriction. During the domestication of wheat, the type of source and sink might be ploidy-dependent with progressive water deficit, but similar interactive relationships. The source-sink ratio of tetraploid species was the largest, while that of hexaploid species was the lowest., 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 Masson SAS. All rights reserved.)

Background: Robotic camera holders can overcome the shortcomings of human assistants, such as shaking and accidental rotation in endoscopic surgery. Robotic camera holder is not affected by the operation time and surgical position and reduces the size of the team. However, there is still controversy over the practicality of robotic camera holders., Material and Methods: We searched PubMed, Web of Science, Embase, Cochrane Library PubMed, Embase, Cochrane Library and Web of Science. The last database search was performed on 30 April 2022. Two reviewers independently reviewed the studies., Results: A total of eight studies ( n  = 698, 354 controls and 344 robotic camera holders) were included in our analysis. The results showed that the robotic camera holder significantly outperformed human assistants on the frequency of lens cleaning (SMD, -0.48; 95% CI, -0.90 to -0.05) and inappropriate movements (MD, -3.57; 95% CI, -4.93 to -2.21). There was no difference in total operation time (MD, 6.99; 95% CI, -2.47 to 16.72), preparation time (MD, 2.43; 95% CI, -0.32 to 5.18) or blood loss (MD, 34.47; 95% CI, -8.05 to 76.98) between the robotic camera holder and human assistant. However, the robotic camera holder was significantly slower in the core operation (MD, 5.06; 95% CI, 1.18 to 8.94), and surgeons had mixed reviews of robotic systems., Conclusions: The robotic camera holder provided the surgeon with a highly stable environment. Although the robotic camera holder will not increase the total time, it still needs to improve the core operation time. There is much room for improvement in robotic camera holders. Further development of devices with intuitive control systems and a greater range of motion will be required to accommodate more complex surgeries.

Despite the great interest in carborane-containing molecules, there is a lack of literature on the generation of central chiralities, via catalytic asymmetric transformations using prochiral carboranyl substrates. Herein, we have synthesized novel optically active icosahedral carborane-containing diols via Sharpless catalytic asymmetric dihydroxylation of carborane-derived alkenes, under mild conditions. The reaction showed a good substrate scope with 74-94% yields and 92->99% ee. This synthetic approach facilitated the creation of two adjacent stereocenters respectively located at the α,β-position of o -carborane cage carbon, with a single syn -diastereoisomer. In addition, the obtained chiral carborane-containing diol product can be transformed to cyclic sulfate and can subsequently undergo a nucleophilic substitution and reduction to obtain the unexpected nido -carboranyl derivatives of chiral amino alcohols in the form of zwitterions.

As the common pathological basis of various cardiovascular diseases, the morbidity and mortality of atherosclerosis (AS) have increased in recent years. Unfortunately, there are still many problems in the treatment of AS, and the prevention and treatment of the disease is not ideal. Up to now, the occurrence and development of AS can roughly include endothelial cell dysfunction, vascular smooth muscle cell proliferation, inflammation, foam cell production, and neoangiogenesis. Among them, endothelial dysfunction, as an early event of AS, plays a particularly important role in promoting the development of AS. In addition, oxidative stress occurs throughout the causes of endothelial dysfunction. Some previous studies have shown that flavonoids derived from herbal medicines are typical secondary metabolites. Due to its structural presence of multiple active hydroxyl groups, it is able to exert antioxidant activity in diseases. Therefore, in this review, we will search PubMed, Web of Science, Elesvier, Wliey, Springer for relevant literature, focusing on flavonoids extracted from herbal medicines, and summarizing how they can prevent endothelial dysfunction by inhibiting oxidative stress. Meanwhile, in our study, we found that flavonoid represented by quercetin and naringenin showed superior protective effects both in vivo and in vitro , suggesting the potential of flavonoid compounds in the treatment of AS., 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 Li, Wang, Duan, Qian, Zhang, He and Li.)

As a type of metalloproteinase, matrix metalloproteinases (MMPs) can be divided into collagenase, gelatinase, stromelysins, membrane-type (MT)-MMPs and heterogeneous subgroups according to their structure and function. MMP contents in the human body are strictly regulated, and their synthesis, activation and inhibition processes should be kept in a certain balance; otherwise, this would result in the occurrence of various diseases. Rheumatoid arthritis (RA) is a known immune-mediated systemic inflammatory disease that is affected by a variety of endogenous and exogenous factors. In RA development, MMPs act as important mediators of inflammation and participate in the degradation of extracellular matrix substrates and digestion of fibrillar collagens, leading to the destruction of joint structures. Interestingly, increasing evidence has suggested that herbal medicines have many advantages in RA due to their multitarget properties. In this paper, literature was obtained through electronic databases, including the Web of Science, PubMed, Google Scholar, Springer, and CNKI (Chinese). After classification and analysis, herbal medicines were found to inhibit the inflammatory process of RA by regulating MMPs and protecting joint structures. However, further preclinical and clinical studies are needed to support this view before these herbal medicines can be developed into drugs with actual application to the disease., 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 Li, Duan, Liang, Huang, Wang, Zhang, Wu, Liu and Peng.)

Spring viremia of carp virus (SVCV) usually be considered as one of the serious in viral diseases of aquaculture, and DNA vaccine with novel delivery mechanism or adjuvant has proven to be a promising and effective strategy to control aquatic animal diseases. In this study, the mannose-modified chitosan, a carrier system for vaccine delivery, were used to developed a chitosan-encapsulated DNA vaccine (CS-M-G) against SVCV, then investigated immune response induced by the vaccine. Our results showed that CS-M-G was confirmed the spherical or elliptical with even distribution and ranging from approximately 50 to 150 nm in size, the expression of the antigen gene could still be detected after 21 d post vaccination. The CS-M-G induces the highest antibody levels in the 20 μg dose group which is about 3 times than naked plasmid group at 21 d post vaccination, and still hold a higher level than control group at 28 d post vaccination. On the side, strongest protection with relative percent survival of 62.1% in the 20 μg CS-M-G group, which could produce significantly higher enzyme activities and up-regulated expression of immune-associated genes than control group. Thus, our results indicate that DNA vaccine loaded with mannose-modified chitosan induces strong immune response and provided an effective protection against SVCV infection, may be helpful and extended for developing more aquatic animal vaccines in the future., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Neurodegenerative disease is a progressive neurodegeneration caused by genetic and environmental factors. Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) are the three most common neurodegenerative diseases clinically. Unfortunately, the incidence of neurodegenerative diseases is increasing year by year. However, the current available drugs have poor efficacy and large side effects, which brings a great burden to the patients and the society. Increasing evidence suggests that occurrence and development of the neurodegenerative diseases is closely related to the mitochondrial dysfunction, which can affect mitochondrial biogenesis, mitochondrial dynamics, as well as mitochondrial mitophagy. Through the disruption of mitochondrial homeostasis, nerve cells undergo varying degrees of apoptosis. Interestingly, it has been shown in recent years that the natural agents derived from herbal medicines are beneficial for prevention/treatment of neurodegenerative diseases via regulation of mitochondrial dysfunction. Therefore, in this review, we will focus on the potential therapeutic agents from herbal medicines for treating neurodegenerative diseases via suppressing apoptosis through regulation of mitochondrial dysfunction, in order to provide a foundation for the development of more candidate drugs for neurodegenerative diseases from herbal medicine., 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 Li, Wang, Duan, Zhang, Guo, Wu and Peng.)

Insect pest chitinases are potential target for developing new insect growth regulators. Piperine was found first to inhibit the insect chitinase ( Of Chi-h) from Ostrinia furnacalis (Asian corn borer) in this work, except for previously reported Of ChtI. Novel piperonyl-tethered rhodanine derivatives 7a - j were rationally designed with piperine as lead and synthesized by introducing a unique rhodanine moiety into the piperine scaffold based on the similar binding cavity of Of ChtI and Of Chi-h. Compared to piperine, compounds 7a - j showed approximately 100- to 400-fold or 110- to 210-fold higher inhibitory capacity against two chitinases, respectively. Molecular mechanism studies indicated that π interactions are crucial for improving inhibitory activity against two chitinases due to the introduction of the conjugated rhodanine ring. Moreover, compounds 7a - c could dramatically inhibit the growth and development of O. furnacalis larvae by in vivo activity evaluation. This study provides novel piperonyl-tethered rhodanine derivatives inhibiting dual chitinases as insect growth regulator candidates.

Atherosclerosis, as a chronic inflammatory response, is one of the main causes of cardiovascular diseases. Atherosclerosis is induced by endothelial cell dysfunction, migration and proliferation of smooth muscle cells, accumulation of foam cells and inflammatory response, resulting in plaque accumulation, narrowing and hardening of the artery wall, and ultimately leading to myocardial infarction or sudden death and other serious consequences. Flavonoid is a kind of natural polyphenol compound widely existing in fruits with various structures, mainly including flavonols, flavones, flavanones, flavanols, anthocyanins, isoflavones, and chalcone, etc. Because of its potential health benefits, it is now used in supplements, cosmetics and medicines, and researchers are increasingly paying attention to its role in atherosclerosis. In this paper, we will focus on several important nodes in the development of atherosclerotic disease, including endothelial cell dysfunction, smooth muscle cell migration and proliferation, foam cell accumulation and inflammatory response. At the same time, through the classification of flavonoids from fruits, the role and potential mechanism of flavonoids in atherosclerosis were reviewed, providing a certain direction for the development of fruit flavonoids in the treatment of atherosclerosis drugs., 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 Li, Wang, Liu, Duan, Zhang, Zhang, Peng, Huang and Wu.)

Background: The interactions between nanoparticles (NPs) and plasma proteins form a protein corona around NPs after entering the biological environment, which provides new biological properties to NPs and mediates their interactions with cells and biological barriers. Given the inevitable interactions, we regard nanoparticle‒protein interactions as a tool for designing protein corona-mediated drug delivery systems. Herein, we demonstrate the successful application of protein corona-mediated brain-targeted nanomicelles in the treatment of glioma, loading them with paclitaxel (PTX), and decorating them with amyloid β-protein (Aβ)-CN peptide (PTX/Aβ-CN-PMs). Aβ-CN peptide, like the Aβ 1-42 peptide, specifically binds to the lipid-binding domain of apolipoprotein E (ApoE) in vivo to form the ApoE-enriched protein corona surrounding Aβ-CN-PMs (ApoE/PTX/Aβ-CN-PMs). The receptor-binding domain of the ApoE then combines with low-density lipoprotein receptor (LDLr) and LDLr-related protein 1 receptor (LRP1r) expressed in the blood-brain barrier and glioma, effectively mediating brain-targeted delivery., Methods: PTX/Aβ-CN-PMs were prepared using a film hydration method with sonication, which was simple and feasible. The specific formation of the ApoE-enriched protein corona around nanoparticles was characterized by Western blotting analysis and LC-MS/MS. The in vitro physicochemical properties and in vivo anti-glioma effects of PTX/Aβ-CN-PMs were also well studied., Results: The average size and zeta potential of PTX/Aβ-CN-PMs and ApoE/PTX/Aβ-CN-PMs were 103.1 nm, 172.3 nm, 7.23 mV, and 0.715 mV, respectively. PTX was efficiently loaded into PTX/Aβ-CN-PMs, and the PTX release from rhApoE/PTX/Aβ-CN-PMs exhibited a sustained-release pattern in vitro. The formation of the ApoE-enriched protein corona significantly improved the cellular uptake of Aβ-CN-PMs on C6 cells and human umbilical vein endothelial cells (HUVECs) and enhanced permeability to the blood-brain tumor barrier in vitro. Meanwhile, PTX/Aβ-CN-PMs with ApoE-enriched protein corona had a greater ability to inhibit cell proliferation and induce cell apoptosis than taxol. Importantly, PTX/Aβ-CN-PMs exhibited better anti-glioma effects and tissue distribution profile with rapid accumulation in glioma tissues in vivo and prolonged median survival of glioma-bearing mice compared to those associated with PMs without the ApoE protein corona., Conclusions: The designed PTX/Aβ-CN-PMs exhibited significantly enhanced anti-glioma efficacy. Importantly, this study provided a strategy for the rational design of a protein corona-based brain-targeted drug delivery system. More crucially, we utilized the unfavorable side of the protein corona and converted it into an advantage to achieve brain-targeted drug delivery., (© 2021. The Author(s).)

Arbuscular mycorrhizal fungus (AMF) is widely viewed as an ecosystem engineer to help plants adapt to adverse environments. However, a majority of the previous studies regarding AMF's eco-physiological effects are mutually inconsistent. To clarify this fundamental issue, we conducted an experiment focused on wheat (Triticum aestivum L.) plants with or without AMF (Funneliformis mosseae) inoculation. Two water regimes (80% and 40% field water capacity, FWC80 (CK) and FWC40 (drought stress) and four planting densities (6 or 12 plants per pot as low densities, 24 or 48 plants per pot as high densities) were designed. AMF inoculation did not show significant effects on shoot biomass, grain yield, and water use efficiency (WUE) under the low densities, regardless of water regimes. However, under the high densities, AMF inoculation significantly decreased shoot biomass, grain yield and WUE in FWC80, while it significantly increased these parameters in FWC40, showing density and/or moisture-dependent effects of AMF on wheat performance. In FWC40, the relationships between reproductive biomass (y-axis) vs. vegetative biomass (x-axis) (R-V), and between grain biomass (y-axis, sink) vs. leaf biomass (x-axis, source) fell into a typical allometric pattern (α > 1, P < 0.001), and the AMF inoculation significantly increased the values of α. Yet in FWC80, they were in an isometric pattern (α ≈ 1, P < 0.001) and AMF addition had no significant effects on α. Similarly, AMF did not significantly change the isometric relationship between leaf biomass (i.e., metabolic rate) and shoot biomass (body size) in FWC80, while it significantly decreased the α of allometric relationship between both of them in FWC40 (α > 1, P < 0.001). We therefore, sketched a generalized model of R-V and sink-source relationships as affected by AMF, in which AMF inoculation might enhance the capabilities of sink acquisition and utilization under drought stress, while having no significant effect under the well watered conditions. Our findings demonstrate dual density- and moisture-dependent effects of AMF on plant development and provide new insights into current ecological applications of AMF as an ecosystem engineer., (© 2021 by the Ecological Society of America.)

Spring viraemia of carp (SVC) caused by spring viraemia of carp virus (SVCV) can infect almost all fish of cyprinids, which bring huge economic losses to aquaculture. Glycoprotein (G), as the most important antigenic determinant protein of SVCV, is widely considered as an effective method against SVCV. In our previous study, we found that G3 (131 aa) is the potential dominant antigen epitope that induces strong immune responses similar to G protein (510 aa). Here, in order to further improve the immune effect, we reported a subunit vaccine (PEG-G3) constructed by PEG-modified dominant epitope protein (G3). The results of serum antibody production, enzyme activities and immune-related genes expression showed that PEG-G3 induces significantly stronger immune protective responses against SVCV than G3. PEG modification significantly increased the serum antibody level of the vaccine, which increased significantly after immunization and reached the peak at 21 day post-vaccination. T-AOC and AKP activities in the lowest concentration group (5 μg) of PEG-G3 were significantly higher than those in the highest concentration group (20 μg) of G3. In PEG-G3 group, the expression of almost all genes increased at least 4 times compared with the control group. After 14-day challenge, the RPS (relative percentage survival) of the highest concentration of PEG-G3 group was 53.6%, while that of G3 group is 38.9%. Therefore, this work shows that PEG modification and dominant epitope screening may be effective methods to improve the immune protective effect of vaccines and to resist the infection of aquatic animal viral diseases., (© 2021 John Wiley & Sons Ltd.)

Background: The effectiveness of bronchial thermoplasty (BT) has been reported in patients with severe asthma. This study compared the effects of BT and cryoballoon ablation (CBA) therapy on the airway smooth muscle (ASM)., Methods: Eight healthy male beagle dogs were included in this experiment. In the preliminary experiment, one dog received BT treatment for both lower lobe bronchus, another dog received CBA treatment for 7 s on the upper and lower lobe of right bronchus, and 30 s on the left upper and lower lobe. The treatments were performed twice at an interval of 1 month. In subsequent experiments, the right lower lobe bronchus was treated with BT, and the left lower lobe bronchus was treated with CBA. The effects of treatment were observed after 1 (n = 3) month and 6 months (n = 3). Hematoxylin-eosin staining, Masson trichrome staining, and immunohistochemical staining were used to compare the effects of BT and CBA therapy on the ASM thickness, collagen fibers synthesis, and M3 receptor expression after treatment. One-way analysis of variance with Dunnett post hoc test was used to analyze the differences among groups., Results: In the preliminary experiment, the ASM ablation effect of 30-s CBA was equivalent to that of 7-s CBA (ASM thickness: 30.52 ± 7.75 μm vs. 17.57 ± 15.20 μm, P = 0.128), but the bronchial mucociliary epithelium did not recover, and large numbers of inflammatory cells had infiltrated the mucosal epithelium at 1-month post-CBA with 30-s freezing. Therefore, we chose 7 s as the CBA treatment time in our follow-up experiments. Compared with the control group (35.81 ± 11.02 μm), BT group and CBA group (13.41 ± 4.40 μm and 4.81 ± 4.44 μm, respectively) had significantly decreased ASM thickness after 1 month (P < 0.001). Furthermore, the ASM thickness was significantly lower in the 1-month post-CBA group than in the 1-month post-BT group (P = 0.015). There was no significant difference in ASM thickness between the BT and CBA groups after six months (9.92 ± 4.42 μm vs. 7.41 ± 7.20 μm, P = 0.540). Compared with the control group (0.161 ± 0.013), the average optical density of the ASM M3 receptor was significantly decreased in 6-month post-BT, 1-month post-CBA, and 6-month post-CBA groups (0.070 ± 0.022, 0.072 ± 0.012, 0.074 ± 0.008, respectively; all P < 0.001). There was no significant difference in the average optical density of ASM M3 receptor between the BT and CBA therapy groups after six months (P = 0.613)., Conclusions: CBA therapy effectively ablates the ASM, and its ablation effect is equivalent to that of BT with a shorter onset time. A neural mechanism is involved in both BT and CBA therapy., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: DNA Polymerase Theta (POLQ) is a DNA polymerase involved in error-prone translesion DNA synthesis (TLS) and error-prone repair of DNA double-strand breaks (DSBs), whose function in hepatocellular carcinoma has not been investigated., Methods: In the present study, both the data collected from the Cancer Genome Atlas (TCGA) and our group's results showed higher POLQ expression in HCC tissues than the para-cancerous tissues, which was associated with higher malignancy and poor prognosis. POLQ knockdown HCC cell model (shPOLQ) was constructed along with the corresponding negative control (shCtrl) through lentivirus infection for loss-of-function study., Results: We found that, upon knockdown of POLQ, the proliferation and migration of HCC cells decreased and apoptosis percentage increased. Moreover, the percentage of cells in G2 phase significantly increased in shPOLQ group compared with shCtrl group. Xenografts in mice grafted with shPOLQ cells grew much slower than that transplanted with shCtrl cells, and expressed lower Ki67 level. Furthermore, an apoptosis-related signaling array was used to explore the involvement of downstream signaling pathways, suggesting the enhanced phosphorylation of HSP27 and JNK, and the de-activation of mTOR, PRAS40, ERK1/2 and STAT3 pathways., Conclusions: Collectively, our study revealed that POLQ may participate in the development of HCC, depletion of which may be a promising treatment strategy for HCC., (© 2021. The Author(s).)

The insect chitinase Of ChtI from the agricultural pest Ostrinia furnacalis (Asian corn borer) is a promising target for green insecticide design. Of ChtI is a critical chitinolytic enzyme for the cuticular chitin degradation at the stage of molting. In this study, piperine, a natural amide compound isolated from black pepper, Piper nigrum L., was discovered for the first time to have inhibitory activity toward Of ChtI. The compound-enzyme interaction was presumed to take place between the piperine benzo[ d ][1,3] dioxole skeleton and subsite -1 of the substrate-binding pocket of Of ChtI. Hence, on the basis of the deduced inhibitory mechanism and crystal structure of the substrate-binding cavity of Of ChtI, compounds 5a - f were designed and synthesized by introducing a butenolide scaffold into the lead compound piperine. The enzymatic activity assay indicated that compounds 5a - f ( K i = 1.03-2.04 μM) exhibited approximately 40-80-fold higher inhibitory activity than the lead compound piperine ( I ) ( K i = 81.45 μM) toward Of ChtI. The inhibitory mechanism of the piperonyl butenolide compounds was elucidated by molecular dynamics, which demonstrated that the introduced butenolide skeleton improved the binding affinity to Of ChtI. Moreover, the in vivo activity assay indicated that these compounds also displayed moderate insecticidal activity toward O. furnacalis . This work introduces the natural product piperine as a starting point for the development of novel insecticides targeting Of ChtI.

Objectives: Postoperative intestinal obstruction is a common postoperative complication with typical symptoms of abdominal pain, vomiting, abdominal distension and constipation. The principal aim of this paper is to provide a full-scale review on the categories and characteristics of postoperative intestinal obstruction, pathophysiology, effects and detailed mechanisms of compounds and monomers from traditional Chinese medicine for treating postoperative intestinal obstruction. Moreover, the possible development and perspectives for future research are also analyzed., Methods: Literature regarding postoperative intestinal obstruction as well as the anti-pio effect of aqueous extracts and monomers from traditional Chinese medicine in the last 20 years was summarized., Key Findings: To date, approximately 30 compounds and 25 monomers isolated from traditional Chinese medicine including terpenes, alkaloids, polysaccharides, flavonoids, phenylpropanoids and quinones, have exerted significant antipio effect. This paper reviews the effective doses, models, detailed mechanisms, and composition of these traditional Chinese medicine compounds, as well as the structure of these monomers. Moreover, challenges existed in the current investigation and further perspectives were discussed as well, hoping to provide a reference for future clinical treatment of postoperative intestinal obstruction and the development of new drugs., Conclusions: Above all, the convincing evidence from modern pharmacology studies powerfully supported the great potential of traditional Chinese medicine in the management of postoperative intestinal obstruction. Regrettably, less attention was currently paid on the mechanisms of traditional Chinese medicine compounds and monomers with antipio effect. Consequently, future study should focus on monomer-mechanism and structure-function relationship., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The extreme climate events such as El Nino seriously threaten crop production and agro-ecological sustainability because of the aggravated environmental stresses worldwide, particularly in sub-Saharan Africa. To address this issue, we investigated the effects of dual plastic film and straw mulching in ridge-furrow (RF) system on wheat productivity, soil carbon and nitrogen stocks in a semiarid area in Kenya from 2015 to 2017. The experimental site represents a typical semiarid continental monsoon climate, and soil type is chromic vertisols. Field experiment with randomized block design consisted of six RF treatments as follows: 1) dual black plastic film and straw mulching (RFbS), 2) dual transparent plastic film and straw mulching (RFtS), 3) sole black plastic film mulching (RFb), 4) sole transparent plastic mulching RF (RFt), 5) sole straw mulching (RFS) and 6) no mulching (CK). The results indicated that seasonal dynamics of rainfall and air temperature fit in with the weather type of El Nino over four growing seasons. RFbS, RFtS, RFb and RFt significantly increased soil water storage (SWS), topsoil temperature, aboveground biomass, grain yield and water use efficiency across four growing seasons (p < 0.05) as compared with CK. Among all the treatments, RFbS and RFtS achieved the greatest SWS, AgB, grain yield and WUE, owing to improved soil hydro-thermal status in both treatments. Critically, RFbS and RFtS significantly improved soil organic carbon and total nitrogen, soil bulk density and the C:N ratio following four growing seasons, comparing with other treatments (p < 0.05). Besides, RFbS and RFtS gave the highest economic returns among all treatments. For the first time, we found that dual plastic film and straw mulching could serve as a sustainable land management to boost wheat productivity and improve soil quality under El Nino in semiarid areas of SSA., 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 © 2020 Elsevier B.V. All rights reserved.)

A simple chiral primary-tertiary diamine derived from C 2 -symmetric 1,2-diphenylethane-1,2-diamine as the organocatalyst in combination with the trifluoroacetic acid additive for the asymmetric Mannich reaction of cyclic N- sulfonyl trifluoromethylated ketimines and methyl ketones afforded the desired product with high enantioselectivity (73-96% ee). The reactions proceeded well for a variety of different substituted cyclic N -sulfonyl trifluoromethyl ketimines and various alkyl methyl ketones, providing access to diverse enantioenriched benzo-fused cyclic sulfamidate N -heterocycles bearing a trifluoromethylated α-tetrasubstituted carbon stereocenter. This study also investigated the diastereoselective reduction of the carbonyl group and ring cleavage reduction of the sulfamidate group of the corresponding Mannich product.

Zanthoxylum bungeanum pericarp is a commonly used herbal medicine in China with effects of anti-inflammatory and analgesic, improving learning and memory ability, while hydroxy- α -sanshool (HAS) is the most important active ingredient of Z. bungeanum pericarps. The purpose of this study was to investigate the neuroprotective effect of HAS and its related possible mechanisms using a H 2 O 2 -stimulated PC12 cell model. CCK-8 assay results showed that HAS had a significant protective effect on H 2 O 2 -stimulated PC12 cells without obvious cytotoxicity on normal PC12 cells. Flow cytometry and fluorescence microscope (DAPI staining and DCFH-DA staining) indicated that HAS could reduce the H 2 O 2 -induced apoptosis in PC12 cells via reduction of intracellular ROS and increase of mitochondrial membrane potential (MMP). Subsequently, results of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) determination suggested that HAS could increase the enzyme activities of SOD, CAT, and GSH-Px whereas it could decrease the MDA contents in H 2 O 2 -stimulated PC12 cells. Furthermore, the western blotting assays showed that HAS could upregulate the expressions of p-PI3k, Akt, p-Akt, and Bcl-2, while it could downregulate the expressions of cleaved caspase-3 and Bax in H 2 O 2 -stimulated PC12 cells. Collectively, it could be concluded according to our results that HAS possesses protective potentials on H 2 O 2 -stimulated PC12 cells through suppression of oxidative stress-induced apoptosis via regulation of PI3K/Akt signal pathway., Competing Interests: There are no conflicts of interest associated with this paper., (Copyright © 2020 Ruo-Lan Li et al.)

Background: The aphid alarm pheromone, (E)-β-farnesene (EβF), is a natural product secreted from the aphid cornicle as a signal to warn companions of danger. Odorant binding proteins (OBPs) are the vital targets in insect signal transduction pathways. To improve bioactivity of EβF as more economic and stable aphid control agents, EβF derivatives containing an active substructure, salicylic acid moiety, were designed, synthesized, and evaluated for their bioactivities in a structure-function study under laboratory conditions., Results: EβF derivatives, (E)-3,7-dimethylocta-2,6-dien-1-yl-2-hydroxy-3-methylbenzoate and (E)-3,7-dimethylocta-2,6-dien-1-yl-2-hydroxy-3-methoxybenzoate showed outstanding aphid-repellent activity at a dose of 5 μg against Acyrthosiphon pisum (repellency proportions of 67.3% and 71.2%, respectively) and Myzus persicae (repellency proportions of 80.0% and 74.4%, respectively) in laboratory. EβF and most of its derivatives bound strongly to ApisOBP9 with a higher affinity than those of the reported potential targets AphisOBP3 and ApisOBP7. The binding affinities to these three ApisOBPs were generally consistent with the in vivo aphid-repellent activity. A molecular docking study suggested that the hydrophobic effect was crucial for the interactions between the derivatives and the OBPs., Conclusion: New EβF derivatives containing salicylic acid moiety and their repellent activity, binding mechanism with three potential OBPs are presented. A new OBP, ApisOBP9, was characterized as a potential EβF and EβF derivatives binding protein for the first time. The hydrophobic nature of these analogues is responsible for their activity. Two analogues 3b and 3e with outstanding aphid-repellent activity could be new leads for aphid control agents., (© 2020 Society of Chemical Industry.)

Insect odorant-binding proteins (OBPs) play key roles in transport odors to receptors and contribute to insect survival. The cooperative interaction of HoblOBP1 and HoblOBP2 in Holotrichia oblita Faldermann (Coleoptera: Melolonthidae) could increase their binding capacity for ligands. In present study, molecular docking results showed that OBP1/OBP2 complex formed a large binding pocket and interacted with the ligands by hydrogen bonds and hydrophobic interactions. Then, nine amino acids for single site mutations, three paired for double sites, and negative control were mutated into alanine successfully by site-directed mutagenesis. Finally, fluorescence binding assays of these mutants showed that breaking one or two pairs of hydrogen bonds between HoblOBP1 and HoblOBP2 or formed with the ligands significantly decrease the binding affinity with the ligands. However, hydrophobic site mutants still showed slight binding affinity to the ligands. Therefore, the three pairs of hydrogen bonds involved in heterodimer formation and the five hydrogen bonding sites in binding pocket played a key role in response to odors in H. oblita. Our findings may promote further understanding of the mechanisms underlying OBP dimer formation and the role of OBP dimers in odor perception and discrimination., (Copyright © 2019 Elsevier B.V. All rights reserved.)

An enantioselective (3+2) cycloaddition of enals and cyclic N-sulfonyl trifluoromethyl ketimines via N-heterocyclic carbene-catalyzed homoenolate addition is described. This reaction can efficiently construct fused N-heterocycle γ-lactams bearing two adjacent chiral centers with >20 : 1 dr and 94-99% ee, with one chiral center as a trifluoromethylated α-tetrasubstituted carbon stereocenter.

Tumor-associated angiogenesis plays a critical role in the pathogenesis of cholangiocarcinoma (CCA). In this study, we examined the biological effects and molecular mechanisms of transcription factor 21 (TCF21) on CCA-associated angiogenesis. TCF21 expression was compared between 15 pairs of peritumor normal tissues and CCA tissues and also between normal bile duct epithelial cells and two CCA cell lines (QBC-939 and TFK-1) using real-time PCR and Western blot. With the use of both CCA cell lines as the model system, we stably expressed TCF21 by lentiviral transduction (Lv-TCF21). In vivo, we monitored xenograft growth from different CCA cells, measured tumor-associated angiogenesis by histological analysis, and determined the expressions and circulatory levels of VEGFA and PDGF-BB by immunohistochemistry and ELISA, respectively. In vitro, we assessed the effects of conditioned medium collected from different CCA cells on the viability, migration, and tube formation of endothelial cells and explored the significance of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), as well as ERK1/2 signaling in this process. TCF21 was significantly downregulated in CCA tissues or cell lines. Ectopic expression of TCF21 in CCA cells inhibited xenograft growth or tumor-associated angiogenesis in vivo and targeted the expression and secretion of proangiogenic factors, VEGFA and PDGF-BB. In vitro, the conditioned medium collected from Lv-TCF21 CCA cells significantly reduced the viability, migration, and tube formation of endothelial cells. On the molecular level, the targeting of PI3K/Akt and ERK1/2 signaling mediated the anti-angiogenic activity of TCF21. TCF21 presents growth-inhibitory and anti-angiogenic activities, and thus the elevation of TCF21 expression may provide therapeutic benefits for CCA. NEW & NOTEWORTHY Transcription factor 21 (TCF21) is downregulated in cholangiocarcinoma (CCA) tissues or cells. TCF21 inhibits the growth of xenografts derived from CCA cells. TCF21 suppresses in vivo tumor-associated angiogenesis. TCF21 targets expression and production of proangiogenic factors from CCA cells. The targeting of phosphatidylinositol 3-kinase/protein kinase B and ERK1/2 signaling mediates the anti-angiogenesis of TCF21.

Interleukin-6 (IL-6) is a multifunctional cytokine that has been implicated in the etiology of cancer. Several case-control studies have been conducted to assess the association of IL-6 -174G>C (rs1800795) polymorphism with the risk of cervical cancer, yet with conflicting conclusions. To derive a more precise estimation of the relationship, we performed this meta-analysis updated to June 2018. A total of seven original publications were identified covering IL-6 -174G>C (rs1800795) polymorphism. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the relationship strengths. Statistically significant relationship was observed between IL-6 -174G>C polymorphism and cervical cancer risk (OR = 0.61, 95% CI: 0.40-0.94 for GG vs. CC, and OR = 0.77, 95% CI: 0.64-0.93 for G vs. C). Moreover, the significant association was found among Asians (OR = 0.46, 95% CI: 0.29-0.75 for GG vs. CC, and OR = 0.70, 95% CI: 0.57-0.89 for G vs. C); hospital-based subgroup (OR = 0.53, 95% CI: 0.38-0.72 for GG vs. CC, and OR = 0.73, 95% CI: 0.61-0.87 for G vs. C); and Hardy-Weinberg equilibrium ≤0.05 (OR = 0.56, 95% CI: 0.37-0.86 for GG vs. GC, and OR = 0.66, 95% CI: 0.47-0.93 for G vs. C). This meta-analysis showed the evidence that the IL-6 -174G>C polymorphism was a low-penetrance susceptibility variant for cervical cancer. Further large-scale case-control studies are needed to confirm these results., (© 2018 The Author(s).)

Ultraviolet absorbing chemicals (UV filters) are widely used in personal care products for protecting human skin and hair from damage by UV radiation. Although these substances are released into the environment during production and consumption processes, little is known about their genotoxicity effects. Our previous studies have shown that benzophenone-type UV filters exhibited acute toxicity on three species of aquatic organisms. Mutagenesis by benzophenone (BP) and benzophenone-1(BP-1) was tested in the present study by the Salmonella typhimurium /reverse mutation assay (Ames assay). All the positive reverse mutations occurred in the absence of the S9 liver extract system for both chemicals. From BP, positive mutation effects on the TA102 strain at doses of 0.05 μg/plate and 0.5 μg/plate were detected. From BP-1, positive mutation effects on the TA97 strain at doses of 0.05 μg/plate and 0.5 μg/plate, and on the TA100 strain at a dose of 0.5 μg/plate, were detected. A mixture of BP and BP-1 exhibited mutagenicity on the TA97 and TA100 strains. For the TA97 strain, the positive mutation results were detected at 10% and 50% of the mixture. For the TA100 strain, the results were detected when the mixture was at 5% and 10%. In the mixture at 5%, the concentrations of BP and BP-1 were 3.5 μg/plate and 14 μg/plate, respectively. In the 10% mixture, the doses of BP and BP-1 were 7 μg/plate and 28 μg/plate, respectively. In the 50% mixture, the doses of BP and BP-1 were 35 μg/plate and 140 μg/plate, respectively. The mixture test results suggested that there was antagonism in mutagenicity between BP and BP-1.

Pheromone binding proteins (PBPs) are widely distributed in insect antennae, and play important roles in the perception of sex pheromones. However, the detail mechanism of interaction between PBPs and odorants remains in a black box. Here, a predicted 3D structure of PBP1 of the serious agricultural pest, Helicoverpa armigera (HarmPBP1) was constructed, and the key residues that contribute to binding with the major sex pheromone components of this pest, (Z)-11- hexadecenal (Z11-16:Ald) and (Z)-9- hexadecenal (Z9-16:Ald), were predicted by molecular docking. The results of molecular simulation suggest that hydrophobic interactions are the main linkage between HarmPBP1 and the two aldehydes, and four residues in the binding pocket (Phe12, Phe36, Trp37, and Phe119) may participate in binding with these two ligands. Then site-directed mutagenesis and fluorescence binding assays were performed, and significant decrease of the binding ability to both Z11-16:Ald and Z9-16:Ald was observed in three mutants of HarmPBP1 (F12A, W37A, and F119A). These results revealed that Phe12, Trp37, and Phe119 are the key residues of HarmPBP1 in binding with the Z11-16:Ald and Z9-16:Ald. This study provides new insights into the interactions between pheromone and PBP, and may serve as a foundation for better understanding of the pheromone recognition in moths.

N,N'-Dialkylbarbituric acids as cyclic malonamide donors were successfully used in the enantioselective Michael addition reaction of enones. Using cinchona alkaloid-based bifunctional squaramide as an organocatalyst, this Michael reaction of N,N'-di-tert-butylbarbituric acid with various enones features a highly enantioselective (91-99% ee) production of the corresponding optically active 5-substituted barbituric acid derivatives. The transformations of the Michael product for the barbituric acid structural unit were realized in two ways, deprotection to remove the N-tert-butyl group and alkylation to produce 5,5-disubstituted barbituric acid derivatives.

The present study aimed to evaluate the diagnostic and prognostic value of Tat-interacting protein 30 (HTATIP2/TIP30) levels alone and in combination with α-fetoprotein (AFP) for the evaluation of hepatocellular carcinoma (HCC) patients. ELISA and immunohistochemical measurements on the serum and tissue of HTATIP2/TIP30 protein from HCC patients and normal controls were made. Receiver operating characteristic (ROC) curve analyses of AFP and HTATIP2/TIP30 were performed, as well as logistic regression analysis of APF combined with HTATIP2/TIP30. Log-rank analysis was used to correlate the prognosis with various levels of HTATIP2/TIP30. HTATIP2/TIP30 levels were significantly lower in the HCC group compared with the control group (4.50±2.63 vs. 9.50±2.04 ng/ml, P<0.001). ROC analysis revealed an optimal cut-off point at 7.27 ng/ml HTATIP2/TIP30 for separating the HCC from the control groups. The sensitivity and specificity were 84.6 and 93.7% (P<0.001), respectively. ROC areas of HTATIP2/TIP30 (0.928, P<0.001) were significantly higher than those for AFP (P<0.001). The area under the curve of the HTATIP2/TIP30 and AFP combination was 0.950 (P<0.001). Log-rank tests revealed that the recurrence-free survival time of the group with HTATIP2/TIP30>5.71 ng/ml was significantly higher than that of the control group (P<0.001). This is the first study to demonstrate that HTATIP2/TIP30 levels in serum may be an effective biomarker for the diagnosis and prognosis of HCC.

The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic biliary tract cancers. However, the exact benefits from the recognized regime are still dismal. We thus elicit this study in an attempt to analyze whether targeted therapy coupled with various chemotherapy could produce improvement of survival benefits. The clinical trials were searched electronically from databases till July 2016 published in English and Chinese. Nine hundred and sixty-four patients from 7 trials were identified in our analysis. The overall analysis achieved a significantly higher overall response rate (ORR) among the patients treated with targeted drugs plus chemotherapy than chemotherapy alone (OR=1.87; 95% CI: 1.37-2.57; P=0.000), but failed in the overall progression-free survival (PFS) [mean difference (MD)=0.63; 95% CI:-0.45-1.72; P=0.26] and overall survival (OS) (MD=-0.67; 95% CI:-2.54-1.20; P=0.49). In the sub analysis, better ORR was obtained with the addition of EGFR (OR=1.75; 95% CI: 1.20-2.56; P=0.004) and VEGFR (OR=2.5; 95% CI: 1.28-4.87; P=0.007) targeted therapy. Furthermore, the sub analysis of EGFR target showed an significant improvement on PFS (MD=1.36; 95% CI: 0.29-2.43; P=0.01). No significant differences were observed in the incidences of neutropenia (OR=1.37; 95% CI: 0.89-2.12), thrombocytopenia (OR=1.40; 95% CI: 0.83-2.39), anemia (OR=1.21; 95% CI: 0.62-2.38), peripheral neuropathy (OR=1.52; 95% CI: 0.81-2.88), increased AST/ALT (OR=1.40; 95% CI: 0.82-2.39) as well as fatigue (OR=1.65; 95% CI: 0.96-2.84) in either of the treatment groups. In conclusion, better ORR associated with chemotherapy combined with targeted therapy (both targeting EGFR and VEGF) is found in the present meta-analysis without the cost of increased unacceptable toxicities, but regretfully not for the OS. The sub-analysis of targeting EGFR instead of VEGF obtains a superior PFS. Otherwise, there is no statistically significant difference in the overall PFS between the combination regime and chemotherapy alone. Given the paucity of favorable data, we need further studies to characterize optimal targeted agents to confirm the potential value to biliary tract cancer.

The lung cancer incidence in the Xuanwei and neighboring region, Yunnan, China, is among the highest in China and is attributed to severe air pollution with high benzo(a)pyrene levels. We systematically and comparatively analyzed DNA methylation alterations at genome and gene levels in Xuanwei lung cancer tissues and cell lines, as well as benzo(a)pyrene-treated cells and mouse samples. We obtained a comprehensive dataset of genome-wide cytosine-phosphate-guanine island methylation in air pollution-related lung cancer samples. Benzo(a)pyrene exposure induced multiple alterations in DNA methylation and in mRNA expressions of DNA methyltransferases and ten-11 translocation proteins; these alterations partially occurred in Xuanwei lung cancer. Furthermore, benzo(a)pyrene-induced DKK2 and EN1 promoter hypermethylation and LPAR2 promoter hypomethylation led to down-regulation and up-regulation of the genes, respectively; the down-regulation of DKK2 and EN1 promoted the cellular proliferation. Thus, DNA methylation alterations induced by benzo(a)pyrene contribute partially to abnormal DNA methylation in air pollution-related lung cancer, and these DNA methylation alterations may affect the development and progression of lung cancer. Additionally, vitamin C and B6 can reduce benzo(a)pyrene-induced DNA methylation alterations and may be used as chemopreventive agents for air pollution-related lung cancer.

Aryl ketones represent problematic substrates for asymmetric Mannich reactions due to a large steric hindrance exhibited by such compound species. A highly enantioselective direct Mannich reaction of aryl methyl ketones with cyclic imine benzo[e][1,2,3]oxathiazine 2,2-dioxides could be successfully carried out utilizing a combination of cinchona alkaloid-derived primary amines with trifluoroacetic acid (TFA); the primary amines feature a superior catalytic efficacy over secondary amines with a variety of sterically hindered carbonyl compounds as substrates. The reaction proceeded well with various cyclic imines in 89-97 % ee and with various aryl methyl ketones in 85-98 % ee. Moreover, the aryl carbonyl of a Mannich product could be transformed to ketoxime, which further undergoes a Beckmann rearrangement to produce an amide compound while maintaining enantioselectivity., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We explored the effects of flurbiprofen axetil on interleukin (IL)-2 and IL-6 levels in postoperative patients with colorectal cancer. A total of 120 patients (American Society of Anesthesiologists I and II) scheduled to undergo colorectal cancer surgery were randomly divided into 3 groups (N = 40 in each group): flurbiprofen axetil group (group F), morphine group (group M), and tramadol group (group T). Group M received 0.1 mg/kg morphine, group T received 1.5 mg/kg tramadol, and group F received 1.5 mg/kg flurbiprofen axetil. Patients in the 3 groups were administered treatments through intravenous injection 10 min before surgery. Serum IL-2 and IL-6 levels were detected. Postoperative adverse reactions were recorded, such as nausea, vomiting, and pruritus. The serum IL-6 level of the 3 groups increased 3 h after surgery. Compared with group M, IL-6 level was higher in group T and group F at 1 day after the surgery, and the differences between group M and the other groups were significant (P < 0.05). Moreover, the incidence of adverse reactions was significantly different among 3 groups (P < 0.05). Flurbiprofen axetil promoted the secretion of IL-2 and inhibited IL-6; additionally, flurbiprofen axetil may have a lower incidence of adverse reactions compared to other treatments.

In a previous study, we found that ERGIC3 was a novel lung cancer-related gene by screening libraries of differentially expressed genes. In this study, we developed a new murine monoclonal antibody (mAb) against ERGIC3. This avid antibody (6-C4) is well suited for immunohistochemistry, immunoblotting and solid-phase immunoassays. Furthermore, we systematically investigated expressions of ERGIC3 in a broad variety of normal human tissues and various types of tumors by immunohistochemistry. In normal human tissues, 6-C4 reacted only in some epithelial cells, such as hepatocytes, gastrointestinal epithelium, ducts and acini of the pancreas, proximal and distal tubules of the kidney, and mammary epithelial cells; however, most normal human tissues were not stained. Moreover, almost all carcinomas that originated from the epithelial cells were positive for 6-C4, whereas all sarcomas were negative. Notably, 6-C4 strongly stained non-small cell lung cancer (NSCLC) cells but did not react with normal lung tissues. Hence, ERGIC3 mAb could be used in histopathological diagnosis and cytopathological testing to detect early-stage NSCLC. We also studied the mechanisms of ERGIC3 regulation in vitro and in vivo by means of bioinformatics analysis, luciferase reporter assay, miRNA expression profiling and miRNA transfection. Results showed that miR-203a downregulation induced ERGIC3 overexpression in NSCLC cells., (© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.)

Objectives: Cytotoxic T-lymphocyte antigen-4 (CTLA4, CD152) is one of the most fundamental immunosuppressive cytokines that inhibits T-cell activation and terminates the T-cell response by blocking signals stimulated via CD28. A number of studies have assessed the association between CTLA-4 +6230G/A polymorphism and cancer risk. However, the results remain controversial., Methods: In the present study, we performed a meta-analysis to derive a more precise estimation of the relationship. A comprehensive literature search was performed using the PubMed database for relevant articles published (updated to November 21, 2013). Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of the association., Results: A total of 13 articles with 14 studies were selected for this meta-analysis, including 4,489 cases and 4,715 controls. Combined analysis revealed no associations between CTLA-4 +6230G/A polymorphism and cancer risk. However, in stratified analysis by cancer type, we found that CTLA-4 +6230G/A polymorphism was associated with the risk of breast cancer (AA vs. AG + GG: OR = 0.77, 95 % CI 0.60-0.97, P = 0.03; AA vs. GG: OR = 0.66, 95 % CI 0.46-0.95, P = 0.02) and cervical cancer (AA vs. AG + GG: OR = 0.56, 95 % CI 0.42-0.75, P < 0.01). Additionally, in subgroup analysis based on ethnicity, significant association was also found between the CTLA-4 +6230G/A polymorphism and cancer risk in the Asian population (AA vs. AG + GG: OR = 0.71, 95 % CI 0.59-0.84, P < 0.01)., Conclusion: This meta-analysis indicates that CTLA-4 +6230G/A polymorphism may be associated with a decreased risk of breast cancer and cervical cancer in Chinese population.

Aims: Intraplaque neovascularization and foam cell infiltration contribute to the development of unstable plaque, leading to thromboembolism and stroke. Cell adhesion molecules (CAMs) have been reported to be involved in the progression of atherosclerosis and plaque vulnerability. The aim of this study was to assess the association of adhesion molecule CD146 with carotid plaque instability., Methods: We collected forty atherosclerotic plaques from 40 patients undergoing carotid endarterectomy. The clinical information of each patient was obtained, and the plaque morphology and characteristics were examined by the ultrasound. The CD146 expressions of the plaques were graded by using semiquantitative scales. The serum level of soluble form of CD146 was detected by enzyme-linked immunosorbent assay (ELISA)., Results: CD146 expression was mainly on the intraplaque blood vessels and infiltrated macrophages. The CD146 expression was strongly correlated with the matrix metalloproteinase-9(MMP-9)expressions (P < 0.001) in the plaques. Soluble CD146 (sCD146) was also elevated in patients with atherosclerotic plaques. There was significant correlation between the increased CD146 expression and sCD146 level (P = 0.0057). sCD146 correlated well with serum MMP-9 (P < 0.0044), IL-6 (P = 0.0044) and high sensitivity C-reactive protein (hsCRP) (P = 0.005)., Conclusions: Adhesion molecules CD146 and its soluble form strongly correlated with the development of inflammation of atherosclerosis and plaque instability. CD146 may be a promising biomarker for monitoring the development and instability of atherosclerotic plaque in patients with carotid diseases., (© 2014 John Wiley & Sons Ltd.)

X-ray repair cross complementing 1 (XRCC1) plays a key role in DNA repair, genetic instability and tumorigenesis. A series of epidemiological studies have examined associations between XRCC1 polymorphisms and cervical cancer risk, but the findings remain inconclusive. We searched three electronic databases (MEDLINE, EMBASE and CNKI) for studies on the association between XRCC1 polymorphisms and cervical cancer risk published before June 2013. Pooled odds ratio (OR) and 95 % confidence interval (CI) were calculated to estimate risk associations. A total of 28 case-control studies from 15 publications with 5,890 cervical cancer cases and 7,626 controls were identified. There was a significant association between rs25487 and cervical cancer risk in Asian populations (Dominant model: OR = 1.25, 95 % CI =1.04-1.50, P = 0.051 for heterogeneity test). After excluding three studies deviated from Hardy-Weinberg equilibrium, we observed a significant association of rs1799782 with cervical cancer risk in all populations and in Asian populations (Recessive model: OR = 1.62 and 1.72, 95 % CI = 1.22-2.14 and 1.29-2.30, P = 0.090 and 0.266 for heterogeneity test, respectively). However, there was no significant association between rs25489 and cervical cancer risk. These findings were further confirmed by false-positive report probability analysis. No publication bias was found by using the funnel plot and Egger's test. This meta-analysis provides strongly statistical evidence for the association between rs1799782 and cervical cancer risk, as well as its association with rs25487 only in Asian populations. However, single large, well-designed prospective studies are needed to confirm these findings.

The innate immune system coordinates the inflammatory response to pathogens. To do so, its cells must discriminate self from non-self utilizing receptors that identify molecules synthesized exclusively by microbes. Toll- like receptors have a crucial role in the detection of microbial infection in mammals and insects. In mammals, they have evolved to recognize conserved products unique to microbial metabolism. These include lipopolysaccharide (LPS), lipotechoic acids, and peptidoglycans (PGN). We show here that TLRs, including TLR2, are expressed on the THP-1 human leukemia cell line. Activation of TLR2 signaling in THP-1 by PGN induces the synthesis of various soluble factors and proteins including interleukin-1β, interleukin-8 and TNF-α and apoptosis of THP-1 with PGN dose and time dependence. Moreover , in this study we show that PGN induces apoptosis of THP-1 cells in a TNF-α-dependent manner. These findings indicate that TLR2 signaling results in a cascade leading to tumor apoptosis and differentiation, which may suggest new clinical prospects using TLR2 agonists as cytotoxic agents in certain cancers.

Objective: To understand the epidemiologic characteristics of endemic typhus in Baoshan city., Methods: Epidemiological data were collected and characteristics were analyzed. IgG antibody (Ab) of Rickettsia mooseri and Orientia tsutsugamushi in serum of patients were tested using both Weil-Felix and IFA method. The Rickettsia mooseri gltA gene, Rickettsia prowazekii gltA gene, Orientia tsutsugamushi 56 kDa protein gene, SFGR ompA gene, Ehrlichia sp. 16S rRNA gene and Anaplasma sp. 16S rRNA gene in spleen of mice were examined by PCR., Results: Fifty-eight endemic typhus cases were found in Longyang district of Baoshan city, during July to August, 2009. Among them, 48 cases were confirmed by clinical diagnosis and 10 cases by laboratory tests. The Ab of Orientia tsutsugamushi Karp serotype was detected in 3 cases from laboratory diagnosis. The spleen samples from 85 Rattus flavipectus were tested using PCR. Of them, 3 samples for Rickettsia mooseri gltA gene showed positive (positive rate was 3.5%), and the homology of 3 Rickettsia mooseri and Rickettsia mooseri Wilmington strain (GenBank U59714.1) was 100% through comparing gene sequence. The results of PCR for detecting Rickettsia prowazekii, Orientia tsutsugamushi, SFGR, Anaplasma sp. and Ehrlichia. sp were all negative., Conclusion: The outbreak of endemic typhus was confirmed in Longyang district of Baoshan city through epidemiological data, clinical diagnosis and laboratory tests. Rickettsia mooseri DNA was detected in the dominant Rattus flavipectus, suggesting that endemic typhus did exist in the local areas.

The aim of this study was to detect DNA damage during expansion ex vivo of umbilical cord blood (UCB) hematopoietic cells and explore the optimal harvest time for culture of CB hematopoietic cells. Mononuclear cells (MNCs) separated from UCB were cultured in a serum-free system supplemented with cytokines and colony forming units were assessed by semisolid culture at the same time. On day 0, 7, 14 and 21 cells were collected for single cell gel electrophoresis (SCGE) analysis and CFUs were also assayed by SCGE, CD34+ cells and CD133+ cells were quantitated by fluorescence-activated cell sorting (FACS). The results showed that the percentage of CD34+ and CD133+ cells was found to be highest after short-term culture (<14 days) and the cord blood DNA damage rate was observed to be less than 5.0% at earlier time points, but at day 21 the DNA damage rate was 28.2%, which was higher than that at day 0 (p=0.000), the tail length of the DNA comet was longer than that at day 0 (p=0.000). The tail lengths of DNA damage on other time points were not significantly different from that at day 0. It is concluded that the DNA damage rate is less than 5.0% after short-term (<14 days) culture of UCB cells ex vivo by using this method. After 14 days DNA damage rate increases significantly. The optimal harvest time of cord blood cells after culture ex vivo would be within 14 days.

Objective: To assess whether preservative-free 1% lidocaine is capable of destroying the LECs in age-related cataract (ARC) in order to provide scientific basis for pursuing safe and effective drugs to eliminate LECs in cataract surgery., Methods: Lens anterior capsule (LAC) specimens were collected from 75 patients (82 eyes) with age-related cataract (ARC), including forty males (44 eyes) and thirty-five females (38 eyes). The age range was 41 - 85 years, the mean age was 67.97 years. There were 34 cortical cataracts, 22 nuclear cataracts and 26 subcapsular cataracts. Capsule specimens were divided into 4 groups: balanced salt solution (BSS) group I and group II (exposed to BSS for 1 minute), lidocaine group (exposed to preservative-free 1% lidocaine for 1 minute) and the control group. Specimens were stained with trypan blue and alizarin red. Photomicrographs of each capsule were taken to observe the viability of LECs and to count the number of necrosis LECs. The pathologic changes of LECs were evaluated by histological methods (11 LAC, 22 pieces) as well as transmission and scanning electron microscopes (5 LAC, 10 pieces). In the control and BSS group I (23 LAC), one half of each capsule specimen was used for the control group and the other half was used for BSS group I. In lidocaine group and BSS group II (43 LAC), one half of each capsule specimen was used for lidocaine group and the other half was used for BSS group II., Results: The rate of necrosis LECs of the anterior capsules in the control group and BSS group I was (56.19 +/- 2.71)% and (57.23 +/- 1.98)%, respectively. The rate of necrosis LECs of the capsules in lidocaine group and BSS group II was (99.86 +/- 8.22)% and (57.64 +/- 7.00)%, respectively. Matching t-test showed that the rate of necrosis LECs in lidocaine group was greater than that in the BSS group II (t = 27.6781, P = 0.0000). There was no significant difference in the number of necrosis LECs between the control group and BSS group I (t = 2.0693, P = 0.0505). There was also no significant difference between males and females; between different cataract, types and between varying age groups (P > 0.05). After irrigated with lidocaine, LECs showed vacuoles and detached from the capsule, and many cavities appeared between the LECs and the capsule. The capsules of BSS and control group showed a normal layer of LECs attached to the capsule. Under transmission and scanning electron microscopes, in lidocaine group, the junction between the LECs and between the cells and the capsule were destroyed; many cells detached from the capsule and the rest arranged loosely. Some LECs dented and many vacuoles emerged, resulting in destruction of the cellular structures., Conclusion: Preservative-free 1% lidocaine may loose the junction between LECs and between the cells and the capsule, and also destroy cellular structures, resulting in degeneration and necrosis of the LECs.