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Yu-Guo Yuan,1,2,* Ya-Xin Zhang,1,* Song-Zi Liu,1,* Abu Musa Md Talimur Reza,3 Jia-Lin Wang,1,2 Ling Li,1,2 He-Qing Cai,1,2 Ping Zhong,1 Il-Keun Kong4 1College of Veterinary Medicine, Yangzhou University, Yangzhou, People’s Republic of China; 2Jiangsu Co-Innovation Center of Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, People’s Republic of China; 3Department of Molecular Biology and Genetics Faculty of Basic Sciences, Gebze Technical University, Kocaeli, Republic of Turkiye; 4Division of Applied Life Science (BK21 Four), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju, Gyeongnam Province, Republic of Korea*These authors contributed equally to this workCorrespondence: Yu-Guo Yuan; Il-Keun Kong, Email yyg9776430@163.com; ikong7900@gmail.comIntroduction: The increasing industrial and biomedical utilization of graphene oxide silver nanoparticles (GO-AgNPs) raises the concern of nanosafety: exposure to the AgNPs or GO-AgNPs increases the generation of reactive oxygen species (ROS), causes DNA damage and alters the expression of whole transcriptome including mRNA, miRNA, tRNA, lncRNA, circRNA and others. Although the roles of different RNAs in epigenetic toxicity are being studied during the last decade, but still we have little knowledge about the role of circle RNAs (circRNAs) in epigenetic toxicity.Methods: Rabbit fetal fibroblast cells (RFFCs) were treated with 0, 8, 16, 24, 32 and 48 μg/mL GO-AgNPs to test the cell viability and 24 μg/mL GO-AgNPs was selected as the experimental dose. After 24 h treatment with 24 μg/mL GO-AgNPs, the level of ROS, malondialdehyde (MDA), superoxide dismutase (SOD), intracellular ATP, glutathione peroxidase (GPx), and glutathione reductase (Gr) were measured in the RFFCs. High-throughput whole transcriptome sequencing was performed to compare the expression of circRNAs, long non-coding RNAs (lncRNA) and mRNA between 24 μg/mL GO-AgNPs-treated RFFCs and control cells. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to validate the accuracy of circRNA sequencing data. Bioinformatics analyses were performed to reveal the potential functional roles and related pathways of differentially expressed circRNAs, lncRNA and mRNA and to construct a circRNA–miRNA–mRNA interaction network.Results: We found that 57 circRNAs, 75 lncRNAs, and 444 mRNAs were upregulated while 35 circRNAs, 21 lncRNAs, and 186 mRNAs were downregulated. These differentially expressed genes are mainly involved in the transcriptional mis-regulation of cancer through several pathways: MAPK signaling pathway (circRNAs), non-homologous end-joining (lncRNAs), as well as PPAR and TGF-beta signaling pathways (mRNAs).Conclusion: These data revealed the potential roles of circRNAs in the GO-AgNPs induced toxicity through oxidative damage, which would be the basis for further research to determine their roles in the regulation of different biological processes.Keywords: circRNAs, GO-AgNPs, oxidative stress, epigenetic toxicity

Background: Novel tuppherapeutic strategies are urgently required to improve clinical outcomes of gastric cancer (GC). KIF15 cooperates with KIF11 to promote bipolar spindle assembly and formation, which is essential for proper sister chromatid segregation. Therefore, we speculated that the combined inhibition of KIF11 and KIF15 might be an effective strategy for GC treatment. Hence, to test this hypothesis, we aimed to evaluate the combined therapeutic effect of KIF15 inhibitor KIF15-IN-1 and KIF11 inhibitor ispinesib in GC. Methods: We validated the expression of KIF11 and KIF15 in GC tissues using immunohistochemistry and immunoblotting. Next, we determined the effects of KIF11 or KIF15 knockout on the proliferation of GC cell lines. Finally, we investigated the combined effects of the KIF11 and KIF15 inhibitors both in vitro and in vivo. Results: KIF11 and KIF15 were overexpressed in GC tissues than in the adjacent normal tissues. Knockout of either KIF11 or KIF15 inhibited the proliferative and clonogenic abilities of GC cells. We found that the KIF15 knockout significantly increased ispinesib sensitivity in GC cells, while its overexpression showed the opposite effect. Further, using KIF15-IN-1 and ispinesib together had a synergistic effect on the antitumor proliferation of GC both in vitro and in vivo. Conclusion: This study shows that the combination therapy of inhibiting KIF11 and KIF15 might be an effective therapeutic strategy against gastric cancer.

The long non-coding telomeric RNA transcript TERRA, in the form of an RNA–DNA duplex, regulates telomere recombination. In a screen for nucleases that affects telomere recombination, mutations in DNA2, EXO1, MRE11 and SAE2 cause severe delay in type II survivor formation, indicating that type II telomere recombination is mediated through a mechanism similar to repairing double-strand breaks. On the other hand, mutation in RAD27 results in early formation of type II recombination, suggesting that RAD27 acts as a negative regulator in telomere recombination. RAD27 encodes a flap endonuclease that plays a role in DNA metabolism, including replication, repair and recombination. We demonstrate that Rad27 suppresses the accumulation of the TERRA-associated R-loop and selectively cleaves TERRA of R-loop and double-flapped structures in vitro. Moreover, we show that Rad27 negatively regulates single-stranded C-rich telomeric DNA circles (C-circles) in telomerase-deficient cells, revealing a close correlation between R-loop and C-circles during telomere recombination. These results demonstrate that Rad27 participates in telomere recombination by cleaving TERRA in the context of an R-loop or flapped RNA–DNA duplex, providing mechanistic insight into how Rad27 maintains chromosome stability by restricting the accumulation of the R-loop structure within the genome.

Purpose. To assess the outcomes of balanced orbital decompression for chorioretinal folds (CRFs) with and without optic disc edema (ODE) in dysthyroid optic neuropathy (DON). Method. A retrospective, interventional study was performed at Sun Yat-sen Memorial Hospital from April 2018 to November 2021. We collected the medical records of 13 patients (24 eyes) with DON and CRFs. Then, we divided them into the ODE group (15 eyes, 62.5%) and the non-ODE group (NODE group, 9 eyes, 37.5%). The valid ophthalmic examination parameters of 8 eyes in each group after balanced orbital decompression were compared at the 6-month follow-up. Results. The mean best corrected visual acuity (BCVA, 0.29 ± 0.27 ) and visual field-mean deviation (VF-MD, − 6.55 ± 3.71 dB) in the ODE group were significantly worse than those in the NODE group ( 0.06 ± 0.15 and − 3.49 ± 1.56 dB; all p < 0.01 ). Six months after orbital decompression, all parameters were found to have significantly improved in both groups, including BCVA and VF-MD (all p < 0.05 ). Moreover, the improvement amplitude of BCVA ( p = 0.020 ) in the ODE group was significantly greater than that in the NODE group. There was no difference in BCVA between the ODE group ( 0.13 ± 0.19 ) and the NODE group ( 0.10 ± 0.13 ). The disc edema of all eyes (8/8 eyes, 100%) in the ODE group was completely mitigated after orbital decompression. The CRF resolution of 2 eyes (2/8 eyes, 25%) in the ODE group and no eyes in the NODE group was mitigated. Conclusions. Balanced orbital decompression can significantly improve visual functions and eliminate optic disc edema in DON patients, whether CRF relieves or not.

In the tandem hydroformylation–acetalization catalyzed by an Ir-catalyst, water as the hydrogen source can inhibit the hydrogenation of olefins, and a catalytic amount of AlCl3 as a promoter can promote acetalization.

Impairment of innate immune cell function and metabolism underlies immunosuppression in sepsis; however, a promising therapy to orchestrate this impairment is currently lacking. In this study, high levels of NOD-like receptor family CARD domain containing-3 (NLRC3) correlated with the glycolytic defects of monocytes/macrophages from septic patients and mice that developed immunosuppression. Myeloid-specific NLRC3 deletion improved macrophage glycolysis and sepsis-induced immunosuppression. Mechanistically, NLRC3 inhibits nuclear factor (NF)-κB p65 binding to nuclear factor of activated T cells 5 (NFAT5), which further controls the expression of glycolytic genes and proinflammatory cytokines of immunosuppressive macrophages. This is achieved by decreasing NF-κB activation-co-induced by TNF-receptor-associated factor 6 (TRAF6) or mammalian target of rapamycin (mTOR)-and decreasing transcriptional co-activator p300 activity by inducing NLRC3 sequestration of mTOR and p300. Genetic inhibition of NLRC3 disrupted the NLRC3-mTOR-p300 complex and enhanced NF-κB binding to the NFAT5 promoter in concert with p300. Furthermore, intrapulmonary delivery of recombinant adeno-associated virus harboring a macrophage-specific NLRC3 deletion vector significantly improved the defense of septic mice that developed immunosuppression upon secondary intratracheal bacterial challenge. Collectively, these findings indicate that NLRC3 mediates critical aspects of innate immunity that contribute to an immunocompromised state during sepsis and identify potential therapeutic targets.

This paper examines the effects and mechanism paths of monetary policy on firms' "short-term debt for long-term investment (SDFLI)" behavior using panel data of Chinese A-share listed firms from 2007-2019. The findings indicate that loose monetary policy suppresses corporate SDFLI behavior by lengthening corporate credit maturity structure through the credit maturity structure channel. In addition, heterogeneity analysis shows that loose monetary policy significantly inhibits the SDFLI behavior of state-owned enterprises(SOEs), non-high-tech firms, and firms in regions with high bank competition levels through the credit term structure channel, and the monetary policy credit term structure channel fails for non-state-owned enterprises(non-SOEs), high-tech firms, and firms in regions with low bank competition levels. The results of the heterogeneity analysis validate the plausibility that monetary policy affects firms' SDFLI behavior through the credit term structure channel.

Ling-Ling Xu,1– 4,&ast; Yao Yan,1– 3,&ast; Yu-Min Yuan,1– 3 Ying Li,1– 3 Jun Jiang,1– 3 Li-Cai Zhang1– 3 1Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, People’s Republic of China; 3NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou, People’s Republic of China; 4Department of Anesthesiology, Nanjing Gaochun People’s Hospital, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li-Cai Zhang, Email licaizhang001@163.comObjective: To assess the receptors of TRPV1 and GABAB1 receptors that were colocalized in cerebrospinal fluid contacting nucleus (CSF-contact nucleus) of chronic inflammatory pain (CIP) rats bringing inspiration for reducing chronic pain.Methods: A rat model of CIP was constructed by plantar injection of complete Freund’s adjuvant (CFA), and the paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured 1, 3, 5, 7, 10, and 14 days after plantar injection. In the first part of the experiment, rats with CIP were divided into the immunofluorescence group and the coimmunoprecipitation (Co-IP) group (n = 6). Rats in the immunofluorescence group were injected with the retrograde tracer CB conjugated with Alexa Fluor 594 into the lateral ventricle two days before the injection of CFA into the plantar surface of the left paw. Three days later, rats that exhibited hyperalgesia were perfused, and their brains were extracted and used for double immunofluorescence staining of the CSF-contacting nucleus. Rats in the Co-IP group were anesthetized and dissected 3 days after CFA injection, and fresh brain segments containing the CSF-contacting nucleus were collected for Co-IP to assess the colocalization of TRPV1 and GABAB1 in the CSF-contacting nucleus (n = 6). In the second part of the experiment, SD rats were divided into the normal saline group (control group) and the CFA group. Fresh CSF-contacting nucleus-containing tissues were collected for Western blot analysis 3 days after plantar injection to observe the changes in TRPV1 and GABAB1 expression in the CSF-contacting nucleus.Results: TRPV1 and GABAB1 were co-expressed in the CSF-contacting nucleus in rats with CIP, and their expression was upregulated.Conclusion: TRPV1 and GABAB1 in the CSF-contacting nucleus are jointly involved in CIP in rats, and there is a direct or indirect link between TRPV1 and GABAB1.Keywords: cerebrospinal fluid-contacting nucleus, TRPV1 receptor, GABAB1 receptor, chronic inflammatory pain

Single-cell interrogation with the solid-state nanoprobes enables understanding of the linkage between cellular behavior and heterogeneity. Herein, inspired by the charge property of the organic molecular probe (OMP), a generic ionic current rectification (ICR) single-cell methodology is established, exemplified by subcellular detection of glutathione (GSH) with high selectivity, sensitivity, and recyclability. The as-developed nanosensor can transduce the subcellular OMP-GSH interaction via a sensitive ionic response, which stems from the superior specificity of OMP and its essential charge property. In addition, the nanosensor exhibits good reversibility, since the subsequent tandem reaction after the recognition can well recover the sensing surface. Given the diverse structures and tailorable charge properties of OMP, this work underpins a new and general method of OMP-based ICR single-cell analysis.

Cancer-related fatigue seriously affects the quality of life of cancer patients, yet few systematic reviews have evaluated the risk factors for cancer-related fatigue in patients with colorectal cancer. We therefore conducted a meta-analysis to assess the risk factors of cancer-related fatigue in patients with colorectal cancer.Literature databases, including PubMed, Ovid, Embase, the Cochrane Central Register of Controlled Trials, the Web of Science, the China National Knowledge Infrastructure, Wanfang, and VIP, were searched from their establishment to September 2021 to identify suitable studies. The quality of included studies was assessed using different tools and evaluated independently by two investigators. Review Manager version 5.4 (Cochrane Collaboration, London, UK) was used for statistical analysis, and sensitivity analysis was conducted.In total, 2642 articles were screened, and data from 25 studies involving 8733 subjects were included in this meta-analysis. After controlling for confounding variables, the following risk factors were associated with cancer-related fatigue: younger age, female sex, low physical activity level, a clinical stage of III or IV, surgery, chemotherapy, insomnia, pain, anxiety, and depression.Younger age, female sex, low physical activity level, a clinical stage of III or IV, chemotherapy, pain, insomnia, anxiety, and depression were identified as risk factors for cancer-related fatigue. Future research should focus on how multidisciplinary teams adopt targeted measures according to these risk factors to better reduce the incidence of cancer-related fatigue.

Background. Eosinophils were common inflammatory cells involved in the occurrence and development of various inflammatory diseases. Multiple recent studies have pointed to the increasingly important role of eosinophils in respiratory diseases. This article aims to compare the expression differences of blood eosinophil counts between asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO). Methods. Patients with asthma, COPD, and ACO who were seen in the First Affiliated Hospital of Guangzhou Medical University from January 2012 to June 2019 were included. We collected information such as age, gender, diagnosis, the eosinophil counts from the medical records. Moreover, the levels of 10 cytokines in the plasma of each group were detected by using the Meso Scale Discovery method. Results. We included 9787 patients with asthma, 15806 patients with COPD, and 831 ACO patients. From our results, it can be first found that eosinophil levels were age-related in the three diseases (asthma and ACO: p < 0.001 ; COPD: P = 0.001 ); in asthma and COPD, the number of eosinophils in males was more significant than that in females (asthma: p < 0.001 ; COPD: p = 0.012 ). Second, asthma patients had higher blood eosinophil counts than those with COPD and ACO ( p < 0.001 ). Moreover, we found out that eosinophil levels were highly expressed in the stable group of all three diseases. Finally, we found that most cytokines in ACO patients showed a downward trend when the level of eosinophils was low, whereas the results were reversed in asthma patients; 7 cytokines had similar trends in COPD and ACO patients. Conclusions. In conclusion, eosinophils have their own unique endotypes in asthma, COPD, and ACO patients, which were reflected in the fluctuation of their levels and changes in cytokine secretion.

Ying Li1,2 &ast;, Jia-Jing Lu1,2 &ast;, Xiao-Yuan Zhong1,2 &ast;, Ying-Yuan Yu1,2 &ast;, Ning Yu,1,2 Yu Wang,1,2 Xue-Mei Yi,1,2 Yang-Feng Ding,1,2 Yu-Ling Shi1,2 1Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Institute of Psoriasis, Tongji University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu-Ling Shi; Yang-Feng Ding, Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, 1278 Road, Shanghai, 200443, People’s Republic of China, Email shiyuling1973@tongji.edu.cn; dingyangfeng@hotmail.comBackground: Data pertaining to biologic agents used for treating psoriasis in real-world settings are lacking at present. To compare drug survival at 52 weeks for a range of biologics used to treat psoriasis under real-world conditions.Methods: This was a retrospective, single-center, observational study of a cohort of patients diagnosed with plaque psoriasis treated using ixekizumab, secukinumab, guselkumab, or adalimumab between January 2020 and December 2021. Baseline demographic characteristics, duration of psoriasis, and prior biological treatments for all patients were recorded. Drug survival rates were analyzed in different patient groups using Kaplan–Meier curves and Log rank tests.Results: In total, this study included 386 plaque psoriasis patients, of whom 70, 175, 36, and 105 were, respectively, treated using ixekizumab, secukinumab, guselkumab, and adalimumab. Over a 52-week period, the overall cumulative drug survival rates for ixekizumab, secukinumab, guselkumab, and adalimumab were 67.1%, 63.0%, 72.2%, and 37.1%, respectively. Lack of efficacy was the primary cause of discontinuation for these biologic therapies, followed by economic burden and adverse event incidence.Conclusion: These results suggest that guselkumab exhibited superior drug survival, drug survival outcomes for ixekizumab and secukinumab were comparable, and significantly better than those of adalimumab in China. Preventing a loss of drug efficacy represents a primary approach to improving biologic drug survival in psoriasis patients.Keywords: biologics, drug survival, real-world, psoriasis, ixekizumab, secukinumab, guselkumab, adalimumab

The Cu2+ in the drinking water has a very serious impact on human health and social ecology. Many countries have the policy on the Cu2+ concentration limitation in drinking water and the industrial Cu2+ emission standards for the treated wastewater. Scientists have developed many methods to remove Cu2+ from wastewater. Among all the adsorption method is widely used due to its high efficacy, feasibility and low cost. The adsorbent is critical to achieving superior Cu2+ removal result. In this paper, Fe3O4/carbon-graphene oxide nanocomposites (Fe3O4@C-GO) were prepared by a hydrothermal method. The Fe3O4@C-GO is the main absorbent to Cu2+ through chemisorption. The specific surface area of Fe3O4@C-GO dramatically increases from 16 m2/g of Fe3O4@C to 62 m2/g, which expands the Cu2+ absorption capacity up to 350 mg/g. Fe3O4 nanoparticles with about 12 nm in diameter are uniformly encapsulated in the C-GO matrix, and therefore the Fe3O4@C-GO can be easily separated from the solution via magnetics. This adsorbent is also very easily recovered by an external magnetic field from the treated wastewater and has high reusability.

The liver is one of the most frequent metastatic sites of breast cancer with a relatively poor prognosis. Systemic chemotherapy is an effective treatment but the efficacy is different between the subtypes of breast cancer. Percutaneous thermal ablation is considered to be a minimally invasive and effective local treatment for breast cancer liver metastases (BCLM). This case report described a patient with BCLM who adopted a strategy of systemic chemotherapy and repeated ultrasound (US) -guided percutaneous thermal ablation procedures. The survival time already reached 8 years till now with the metastases well-controlled and acceptable life quality was achieved.

Neural tube defect (NTD) is the most common and severe embryopathy causing embryonic malformation and even death associated with gestational diabetes mellitus (GDM). Leu-Pro-Phe (LPF) is an antioxidative tripeptide isolated from hydrolysates of corn protein. However, the biological activity of LPF in vivo and in vitro remains unclear. This study is aimed at investigating the protective effects of tripeptide LPF against NTD in the high glucose exposure condition and delineate the underlying biological mechanism. We found that LPF alleviated NTD in the high glucose-exposed chicken embryo model. In addition, DF-1 chicken embryo fibroblast was loaded with high glucose for induction of oxidative stress and abnormal O-GlcNAcylation in vitro. LPF significantly decreased accumulation of reactive oxygen species and content of malondialdehyde in DF-1 cells but increased the ratio of reduced glutathione and oxidized glutathione in chick embryo. Oxygen radical absorbance capacity results showed that LPF itself had good free radical scavenging capacity and could enhance antioxidant activity of the cell content. Mechanistic studies suggested that the resistance of LPF to oxidative damage may be related to promotion of NRF2 expression and nuclear translocation. LPF alleviated the overall O-GlcNAcylation level of cellular proteins under high glucose conditions and restored the level of Pax3 protein. Collectively, our findings indicate that LPF peptide could act as a nutritional supplement for the protection of development of embryonic neural tube affected by GDM.