Search

Feng Qin,1,2 Mingxing Wang,1,2 Jibing Qiu,1,2 Jinbao Guo1,2 1The Changzhou Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, People’s Republic of China; 2Department of Otorhinolaryngology, Changzhou Third People’s Hospital, Changzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Jinbao Guo, Department of Otorhinolaryngology, Changzhou Third People’s Hospital, 300 Lanling North Road, Changzhou, Jiangsu, People’s Republic of China, 213000, Email cz3ent@163.comPurpose: To explore the relationship between hyperlipidemia and full-frequency idiopathic sudden sensorineural hearing loss (FFHL).Patients and Methods: A total of 145 FFHL patients admitted from September 2021 to May 2024 were analyzed. Eighty-five patients with hyperlipidemia and 60 patients with normal serum lipids statistically analyze the patient’s gender, age, onset time, accompanying symptoms, and serum lipids. Measure the pure tone hearing threshold before and after treatment, and calculate the average increase in hearing threshold. Compare the correlation between various factors and prognosis.Results: The hyperlipidemia group had a higher proportion of males (P=0.043) and vertigo (P=0.044) compared to the control group, while other information between the two groups lacked statistical significance. Effective patients (n=44) in the hyperlipidemia group showed significant differences in vertigo (P=0.020), age (P=0.032), and onset (P=0.030) compared to ineffective patients (n=41). Analysis showed that these were independent correlated factors affecting prognosis. Other indicators, including serum lipids, have no significance in predicting the prognosis of patients with hyperlipidemia and complete frequency decline in hearing loss.Conclusion: Patients with hyperlipidemia have higher rates of males and vertigo. The age, onset, and vertigo of patients with hyperlipidemia are related to prognosis, while various lipid indicators are not related to the prognosis of sudden hearing loss.Keywords: hyperlipidemia, idiopathic sudden sensorineural hearing loss, full frequency hearing loss

Xinling Zhao,1,2,&ast; Huijin Jie,3,&ast; Jun Wang,1 Yu Liu,4 Yilin Liu,2 Fuyi Qin,2 Qing Long,2 Xi Hou,5 Xin-Wen Zhang,6 Wenzhi Wu,7 Xiaoqin Wu,2 Jing Li,8 Yong Zeng2 1Department of Clinical Psychology, People’s Hospital of Chongqing Liang Jiang New Area, Chongqing, People’s Republic of China; 2Department of Psychiatry, the Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Haining Fourth People’s Hospital, Haining, People’s Republic of China; 4Department of Psychiatry, the First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 5Department of Clinical Psychology, The Sixth Affiliated Hospital of Kunming Medical University, Yuxi, People’s Republic of China; 6Department of Psychiatry, Hong He Second People’s Hospital, Jian Shui, People’s Republic of China; 7Faculty of psychology, Beijing Normal University, Beijing, People’s Republic of China; 8Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Li; Yong Zeng, Email lijingjingjing222@163.com; zengyong@kmmu.edu.cnBackground: Adolescents with major depressive (MDD) episodes associated with childhood trauma have a poorer response to treatment and a higher risk of suicide. The underlying etiology is unclear. Brain-derived neurotrophic factor (BDNF) could improve depressive symptoms by down-regulating mammalian target of rapamycin (mTOR) signaling pathways, which was involved in adverse environmental stimuli during neurodevelopment. BDNF and mTOR have not been reported simultaneously in adolescents with major depressive episodes associated with childhood trauma.Methods: Childhood Trauma Questionnaire-Short Form (CTQ-SF), Children’s Depression Inventory (CDI) and Children’s Depression Rating Scale-Revised (CDRS-R) were used to evaluate the recruited adolescents with major depression episodes. Serum BDNF and p-mTOR levels were measured by ELISA in 31 adolescents with major depression episodes with childhood trauma and 18 matched healthy control.Results: The serum levels of BDNF were significantly lower (p< 0.001); and the serum levels of p-mTOR were high (p=0.003) in the adolescents with the first episode of major depressive episode accompanied by childhood trauma. Of the 31 adolescents with major depressive episodes, 17 had suicide or self-injury. Compared with the healthy control group, the serum levels of BDNF in patients with suicide or self-injury were lower than those without suicide or self-injury(p< 0.001); the serum levels of p-mTOR were higher than those without suicide or self-injury (p=0.01). While in patients without suicide or self-injury, only serum p-mTOR was significantly higher than that in healthy group (p=0.028). BDNF was negatively correlated with CDRS-R (r=− 0.427, p=0.006), p-mTOR was positively correlated with CDI (r=0.364, p=0.048). According to Receiver Operating Characteristic Curve (ROC), the combination of serum BDNF and p-mTOR levels have better diagnostic value.Conclusion: Neurotrophic and signaling pathways, involving BDNF and p-mTOR, may play a role in adolescent MDD with a history of childhood trauma, especially patients with suicide and self-injury tendencies.Keywords: brain-derived neurotrophic factor, p-mTOR, major depressive disorder, suicide, adolescent, childhood trauma

Fuxun Zhang1,2 &ast;, Yang Xiong1,2 &ast;, Feng Qin,1 Jiuhong Yuan1,2 1Andrology Laboratory, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiuhong Yuan, Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China, Email jiuhongyuan2107@163.comAbstract: The meaning of sleep has puzzled people for millennia. In modern society, short sleep duration is becoming a global problem. It has been established that short sleep duration can increase the risk of several diseases, such as cardiovascular and metabolic diseases. Currently, a growing body of research has revealed a possible link between sleep disorders and erectile dysfunction (ED). However, the mechanisms linking short sleep duration and ED are largely unknown. Thus, we provide a review of clinical trials and animal studies. In this review, we propose putative pathways connecting short sleep duration and ED, including neuroendocrine pathways and molecular mechanisms, aiming to pave the way for future research. Meanwhile, the assessment and improvement of sleep quality should be recommended in the diagnosis and treatment of ED patients.Keywords: erectile dysfunction, molecular mechanisms, sleep disorder, short sleep duration, signaling pathway

Yang Yao,1,2,* Xinggen Fang,1,* Jinlong Yuan,1 Feiyun Qin,1 Tao Yu,1 Dayong Xia,1,3 Zhenbao Li,1 Niansheng Lai1,3 1Department of Neurosurgery, First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, 241001, Anhui Province, People’s Republic of China; 2Department of Nursing, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, 241001, Anhui Province, People’s Republic of China; 3Key Laboratory of Non-Coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu, 241001, Anhui Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Niansheng Lai; Zhenbao LiDepartment of Neurosurgery, First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), 2 West Zheshan Road, Wuhu, 241001, Anhui Province, People’s Republic of ChinaTel +86-15155308793Fax +86-05535739594Email mlns@wnmc.edu.cn; zhenbaoli123@126.comObjective: Aneurysmal subarachnoid hemorrhage (aSAH) is a severe form of stroke characterized by high rates of mortality and disability. Identifying circulating biomarkers is helpful to improve outcomes. In this study, for the first time, we identify interleukin-6 (IL-6) in cerebrospinal fluid (CSF) small extracellular vesicles (sEVs) as potential biomarkers for prognosis of aSAH.Methods: We extracted small extracellular vesicles from the CSF of 103 aSAH patients and 40 healthy controls in a prospective observational study. Subsequently, we measured IL-6sEVs levels using an enzyme-linked immunosorbent assay. Results were statistically analyzed to determine the function of IL-6sEVs for disease monitoring of aSAH.Results: CSF IL-6 sEVs showed distinct pattern differences between healthy controls and aSAH patients. The concentration of IL-6sEVs in CSF is significantly correlated with the severity of aSAH patients. The areas under the receiver operating characteristic curves of IL-6sEVs for identifying severe aSAH patient from aSAH patients were 0.900. After multivariate logistic regression analysis, IL-6sEVs were associated with neurological outcome at 1 year. IL-6sEVs levels were greater and positively associated with disease processes and outcome.Conclusion: There is a neuroinflammatory cascade in aSAH patients. IL-6sEVs in CSF may be a biomarker for the progression of aSAH.Keywords: subarachnoid hemorrhage, cerebrospinal fluid, small extracellular vesicles, interleukin-6, biomarker

Yun Liu,1,* Ying-Ling Miao,2,* Feng Qin,1 Cen Cao,1 Xiao-Lin Yu,1 Yu-Han Wu,1 Tian-Lu Wang,1 Ruo-Gu Xu,1 Liu Zhao,3 Fan Wu,1 Zheng-Chuan Zhang,1 Jia-Min Yang,1 Yang Yang,1 Xin Xie,1 Li-Ming Zhang,2 Fei-Long Deng1 1Department of Oral Implantology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 2School of Materials Science and Engineering, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 3School of Chemistry, Beihang University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-Ming ZhangSchool of Materials Science and Engineering, Sun Yat-Sen University, No. 135, Xingang Xi Road, Guangzhou 510275, People’s Republic of ChinaTel +86 020-84112354Email ceszhlm@mail.sysu.edu.cnFei-Long DengDepartment of Oral Implantology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, No. 56, Lingyuan Xi Road, Guangzhou 510000, People’s Republic of ChinaTel +86 020-83863002Email dengfl@mail.sysu.edu.cnBackground: Critical-sized bone defects raise great challenges. Zein is of interest for bone regeneration, but it has limited ability to stimulate cell proliferation. In this regard, a poly (aspartic acid) (PAsp)-zein hybrid is promising, as PAsp can promote rat bone marrow stromal cell (rBMSCs) proliferation and osteogenic differentiation. This research aimed to develop electrospun PAsp-modified zein nanofibers to realize critical-sized bone defects repair.Methods: Three groups of PAsp-modified zein nanofibers were prepared, they were PAsp grafting percentages of 0% (zein), 5.32% (ZPAA-1), and 7.63% (ZPAA-2). Using rBMSCs as in vitro cell model and SD rats as in vivo animal model, fluorescence staining, SEM, CCK-8, ALP, ARS staining, μCT and histological analysis were performed to verify the biological and osteogenic activities for PAsp-modified zein nanofibers.Results: As the Asp content increased from 0% to 7.63%, the water contact angle decreased from 129.8 ± 2.3° to 105.5 ± 2.5°. SEM, fluorescence staining and CCK-8 assay showed that ZPAA-2 nanofibers had a superior effect on rBMSCs spreading and proliferation than did zein and ZPAA-1 nanofibers, ALP activity and ARS staining showed that ZPAA-2 can improve rBMSCs osteogenic differentiation. In vivo osteogenic activities was evaluated by μCT analysis, HE, Masson and immunohistochemical staining, indicating accelerated bone formation in ZPAA-2 SD rats after 4 and 8 weeks treatment, with a rank order of ZPAA-2 > ZPAA-1 > zein group. Moreover, the semiquantitative results of the Masson staining revealed that the maturity of the new bone was higher in the ZPAA-2 group than in the other groups.Conclusion: Electrospun PAsp-modified zein can provide a suitable microenvironment for osteogenic differentiation of rBMSCs, as well as for bone regeneration; the optimal membrane appears to have a PAsp grafting percentage of 7.63%.Keywords: electrospun, osteogenesis, poly (aspartic acid), zein

Fenju Qin,1,2 Tao Shen,1 Honglong Cao,3 Junchao Qian,4 Dan Zou,1 Mingkang Ye,1 Hailong Pei21Department of Biotechnology and Bioengineering, Suzhou University of Science and Technology, Suzhou 215009, People’s Republic of China; 2School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, People’s Republic of China; 3School of Electronic & Information Engineering, Soochow University, Suzhou 215006, People’s Republic of China; 4Jiangsu Key Laboratory for Environment Functional Materials, Suzhou University of Science and Technology, Suzhou 215009, People’s Republic of ChinaIntroduction: The ratio of Ce3+,/Ce4+, in their structure confers unique functions on cerium oxide nanoparticles (CeO2NPs) containing rare earth elements in scavenging free radicals and protecting against oxidative damage. The potential of CeO2NPs to protect testosterone synthesis in primary mouse Leydig cells during exposure to 1,800 MHz radiofrequency (RF) radiation was examined in vitro.Methods: Leydig cells were treated with different concentrations of CeO2NPs to identify the optimum concentration for cell proliferation. The cells were pretreated with the optimum dose of CeO2NPs for 24 hrs and then exposed to 1,800 MHz RF at a power density of 200.27 μW/cm2, (specific absorption rate (SAR), 0.116 W/kg) for 1 hr, 2 hrs, or 4 hrs. The medium was used to measure the testosterone concentration. The cells were collected to determine the antioxidant indices (catalase [CAT], malondialdehyde [MDA], and total antioxidant capacity [T-AOC]), and the mRNA expression of the testosterone synthase genes (Star, Cyp11a1, and Hsd-3β) and clock genes (Clock, Bmal1, and Rorα).Results: Our preliminary result showed that 128 μg/mL CeO2NPs was the optimum dose for cell proliferation. Cells exposed to RF alone showed reduced levels of testosterone, T-AOC, and CAT activities, increased MDA content, and the downregulated genes expression of Star, Cyp11a1, Hsd-3β, Clock, Bmal1, and Rorα. Pretreatment of the cells with 128 μg/mL CeO2NPs for 24 hrs followed by RF exposure significantly increased testosterone synthesis, upregulated the expression of the testosterone synthase and clock genes, and increased the resistance to oxidative damage in Leydig cells compared with those in cells exposed to RF alone.Conclusion: Exposure to 1,800 MHz RF had adverse effects on testosterone synthesis, antioxidant levels, and clock gene expression in primary Leydig cells. Pretreatment with CeO2NPs prevented the adverse effects on testosterone synthesis induced by RF exposure by regulating their antioxidant capacity and clock gene expression in vitro. Further studies of the mechanism underlying the protective function of CeO2NPs against RF in the male reproductive system are required.Keywords: CeO2NPs radiofrequency radiation, Leydig cell, testosterone synthesis, clock genes, antioxidant

Fen Qin,1,* Quan Wang,2,* Chunlian Zhang,1 Caiyun Fang,1 Liping Zhang,1 Hailin Chen,1 Mi Zhang,3 Fei Cheng3 1Department of Obstetrics and Gynecology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China; 2Department of Stomatology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China; 3Department of Cardiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China *These authors contributed equally to this work Purpose: Antifungal drugs are used frequently in the treatment of vulvovaginal candidiasis (VVC), but have shown controversial results. In this study, we aimed to evaluate the effectiveness of different antifungal drugs in the treatment of VVC and to provide an evidence-based reference for clinical use.Methods: The published studies on the effectiveness of antifungal drugs in the treatment of VVC (up to April 2018) were retrieved from PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov. We sifted through the literature according to Patients, Interventions, Comparisons and Outcomes principle, extracted data on the basic characteristics of the study, and evaluated the quality of included studies. We used R software for statistical analysis.Results: In total, 41 randomized controlled trials were included in this meta-analysis. The relative risk of VVC associated with ten drugs, including placebo, fluconazole, clotrimazole, miconazole, itraconazole, ketoconazole, econazole, butoconazole, terbinafine, and terconazole, was analyzed. The following drugs appeared to show more efficacy than placebo in the treated patients: fluconazole (OR =6.45, 95% CrI 4.42–9.41), clotrimazole (OR =2.99, 95% CrI 1.61–5.55), miconazole (OR =5.96, 95% CrI 3.17–11.2), itraconazole (OR =2.29, 95% CrI 1.21–4.33), ketoconazole (OR =2.40, 95% CrI 1.55–3.71), butoconazole (OR =1.18, 95% CrI 1.06–1.31), and terconazole (OR =5.60, 95% CrI 2.78–11.3). The value of surface under the cumulative ranking curve of each drug was as follows: placebo (0.5%), fluconazole (91.5%), clotrimazole (61.8%), miconazole (33.8%), itraconazole (50.5%), ketoconazole (42.8%), econazole (46.8%), butoconazole (82.2%), terbinafine (20.9%), and terconazole (65.0%).Conclusion: Antifungal drugs are effective in the treatment of VVC. Fluconazole appeared to be the best drug for the treatment of VVC according to our analysis. Keywords: vulvovaginal candidiasis, antifungal drugs, randomized controlled trials, network meta-analysis

Wanan Yang,1 Houde Dai,2 Yong He,1 Fengqing Qin1 1School of Computer and Information Engineering, Yibin University, Yibin, Sichuan, People's Republic of China; 2Quanzhou Institute of Equipment Manufacturing, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Quanzhou, People's Republic of China Abstract: Wireless capsule endoscope achieved great success, however, the maneuvering of wireless capsule endoscope is challenging at present. A magnetic driving instrument, including two bar magnets, a stepper motor, a motor driver, a motor controller, and a power supplier, was developed to generate rotational magnetic fields. Permanent magnet ring, magnetized as S and N poles radially and mounted spiral structure on the surface, acted as a capsule. The maximum torque passing to the capsule, rotational synchronization of capsule and motor, and the translational speed of capsule, were measured in ex vivo porcine large intestine. The experimental results illustrate that the rotational movement of the spiral-type capsule in the intestine is feasible and the cost of the magnetic driving equipment is low. As a result, the solution is promising in the future controllability. Keywords: wireless capsule endoscope, magnet ring, magnetic driving, spiral structure, torque

Yiwen Wang,* Fei Qin,* Haina Tan, Yan Zhang, Miao Jiang, Mei Lu, Xin Yao School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Carboxymethyl-β-cyclodextrin (CMβ-CD)-modified glycol chitosan (GCS) nanoparticles (GCS-CMβ-CD NPs) were synthesized, and their pH-sensitive drug-release properties were investigated. GCS-CMβ-CD NPs could encapsulate doxorubicin hydrochloride (DOX), and the encapsulation efficiency and loading capacity increased with the amount of CMβ-CD. Drug-release studies indicate that DOX released was greater in acidic medium (pH 5.0) than in weakly basic medium (pH 7.4). The mechanism underlying the pH-sensitive properties of the carrier was analyzed. Finally, the MCF-7 (human breast cancer) and SW480 cell lines (human colon cancer) were used to evaluate the cytotoxicity of the NPs. The drug-loaded carriers show good inhibition of the growth of cancer cells compared with free DOX, and the carriers have good biocompatibility. In addition, the drug-loaded NPs have sustained drug-release properties. All these properties of the newly synthesized GCS-CMβ-CD NPs suggest a promising potential as an effective anticancer drug-delivery system for controlled drug release. Keywords: MCF-7, SW480, surface plasmon resonance, encapsulation efficiency, loading capacity, cell viability

Fei Qin,1,* Yun Ma,1,* Xiao Li,2 Xian Wang,1 Yuanyi Wei,1 Chuqi Hou,3 Si Lin,1 Lianbing Hou,1 Chengxi Wang4 1Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, 2Department of Pharmacy, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, 3Department of Pharmacology, Southern Medical University, 4Department of Pharmacology, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Up to 90% of patients develop adhesion following laparotomy. Upregulating fibrinolysis within the peritoneum reduces adhesions. Tanshinone IIA (Tan IIA) promotes fibrinolysis in hepatic fibrosis and the cardiovascular system and may play a role in preventing adhesions. We report preparation and characterization of liquid nanoparticles of Tan IIA for intravenous administration and investigate its feasibility in clinical practice. Tan IIA liquid nanoparticles (Tan IIA-NPs) were prepared using the emulsion/solvent evaporation method. Adhesions were induced in Sprague–Dawley rats by injuring the parietal peritoneum and cecum, followed by intravenous administration of various Tan IIA-NP dosages. The adhesion scores for each group were collected 7 days after the initial laparotomy. The activity of tissue-type plasminogen activator (tPA) was measured from the peritoneal lavage fluid. The messenger RNA and protein expression levels of plasminogen activator inhibitor-1 (PAI-1) were measured by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. TGF-β1 and collagen I expressions were measured immunohistochemically in the ischemic tissues. The effects of Tan IIA-NPs and free-Tan IIA on tPA and PAI-1 were measured in vitro in TGF-β1-induced HMrSV5 cells. Tan IIA-NPs exhibited small particle size, high encapsulation efficiency, good stability for storage, and safety for intravenous administration. Tan IIA-NPs were effective in preventing adhesion. Tan IIA-NPs increased tPA activity in peritoneal lavage fluid, and tPA mRNA and protein expression, and decreased PAI-1 mRNA and protein expression in the ischemic tissues. Moreover, Tan IIA-NPs decreased TGF-β1 and collagen I expressions in the ischemic tissues. Tan IIA-NPs administered via tail veins upregulated fibrinolysis in the peritoneum. In vitro studies showed that these effects may be mediated by the TGF-β signal pathway. Keywords: peritoneal fibrinolysis, tissue-type plasminogen activator, plasminogen activator inhibitor-1

Wanan Yang,1 Yan Li,2 Fengqing Qin11School of Computer and Information Engineering, 2Computer Science and Technology Institute, Yibin University, Yibin, People's Republic of ChinaAbstract: To actively maneuver a robotic capsule for interactive diagnosis in the gastrointestinal tract, visualizing accurate position and orientation of the capsule when it moves in the gastrointestinal tract is essential. A possible method that encloses the circuits, batteries, imaging device, etc into the capsule looped by an axially magnetized permanent-magnet ring is proposed. Based on expression of the axially magnetized permanent-magnet ring's magnetic fields, a localization and orientation model was established. An improved hybrid strategy that combines the advantages of particle-swarm optimization, clone algorithm, and the Levenberg–Marquardt algorithm was found to solve the model. Experiments showed that the hybrid strategy has good accuracy, convergence, and real time performance.Keywords: localization, permanent-magnet ring, robotic capsule, hybrid strategy

Xiao Li, Fei Qin, Li Yang, Liqian Mo, Lei Li, Lianbing Hou Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China Abstract: Targeted nanoparticle (NP) delivery vehicles are emerging technologies, the full potential of which has yet to be realized. Sulfatide is known to bind to extracellular matrix glycoproteins that are highly expressed in breast tumors. In this study, we report for the first time the combination of sulfatide and lipid perfluorooctylbromide NPs as a targeted breast cancer delivery vehicle for paclitaxel (PTX). PTX-sulfatide-containing lipid perfluorooctylbromide NPs (PTX-SNPs) were prepared using the emulsion/solvent evaporation method. PTX-SNPs exhibited a spherical shape, small particle size, high encapsulation efficiency, and a biphasic release in phosphate-buffered solution. The cytotoxicity study and cell apoptosis assay revealed that blank sulfatide-containing lipid perfluorooctylbromide NPs (SNPs) had no cytotoxicity, whereas PTX-SNPs had greater EMT6 cytotoxicity levels than PTX-lipid perfluorooctylbromide NPs (PTX-NPs) and free PTX. An in vitro cellular uptake study revealed that SNPs can deliver greater amounts of drug with more efficient and immediate access to intracellular targets. In vivo biodistribution measured using high-performance liquid chromatography confirmed that the PTX-SNPs can target breast tumor tissues to increase the accumulation of PTX in these tissues. The in vivo tumor inhibition ability of PTX-SNPs was remarkably higher than PTX-NPs and free PTX. Furthermore, toxicity studies suggested that the blank SNPs had no systemic toxicity. All results suggested that SNPs may serve as efficient PTX delivery vehicles targeting breast carcinoma. Keywords: perfluorooctylbromide nanoparticles, paclitaxel, drug delivery, targeting, antitumor efficacy

To understand the molecular mechanisms that mediate the anti-hepatitis B virus (HBV) effect of interferon (IFN) therapy, we conduct high-throughput bimolecular fluorescence complementation screening to identify potential physical interactions between the HBx protein and 145 IFN-stimulated genes (ISGs). Seven HBx-interacting ISGs have consistent and significant inhibitory effects on HBV replication, among which TRIM5γ suppresses HBV replication by promoting K48-linked ubiquitination and degradation of the HBx protein on the K95 ubiquitin site. The B-Box domain of TRIM5γ under overexpression conditions is sufficient to trigger HBx degradation and is responsible both for interacting with HBx and recruiting TRIM31, which is an ubiquitin ligase that triggers HBx ubiquitination. High expression levels of TRIM5γ in IFN-α-treated HBV patients might indicate a better therapeutic effect. Thus, our studies identify a crucial role for TRIM5γ and TRIM31 in promoting HBx degradation, which may facilitate the development of therapeutic agents for the treatment of patients with IFN-resistant HBV infection.

Zika virus (ZIKV) has become a public health threat due to its global transmission and link to severe congenital disorders. The host immune responses to ZIKV infection have not been fully elucidated, and effective therapeutics are not currently available. Herein, we demonstrated that cholesterol-25-hydroxylase (CH25H) was induced in response to ZIKV infection and that its enzymatic product, 25-hydroxycholesterol (25HC), was a critical mediator of host protection against ZIKV. Synthetic 25HC addition inhibited ZIKV infection in vitro by blocking viral entry, and treatment with 25HC reduced viremia and conferred protection against ZIKV in mice and rhesus macaques. 25HC suppressed ZIKV infection and reduced tissue damage in human cortical organoids and the embryonic brain of the ZIKV-induced mouse microcephaly model. Our findings highlight the protective role of CH25H during ZIKV infection and the potential use of 25HC as a natural antiviral agent to combat ZIKV infection and prevent ZIKV-associated outcomes, such as microcephaly.

New influenza vaccines that provide effective and broad protection are desperately needed. Live attenuated viruses are attractive vaccine candidates because they can elicit both humoral and cellular immune responses. However, recent formulations of live attenuated influenza vaccines (LAIVs) have not been protective. We combined high-coverage transposon mutagenesis of influenza virus with a rapid high-throughput screening for attenuation to generate W7-791, a live attenuated mutant virus strain. W7-791 produced only a transient asymptomatic infection in adult and neonatal mice even at doses 100-fold higher than the LD50 of the parent strain. A single administration of W7-791 conferred full protection to mice against lethal challenge with H1N1, H3N2, and H5N1 strains, and improved viral clearance in ferrets. Adoptive transfer of T cells from W7-791-immunized mice conferred heterologous protection, indicating a role for T cell-mediated immunity. These studies present an LAIV development strategy to rapidly generate and screen entire libraries of viral clones.

Chirality of materials are known to affect optical, magnetic and electric properties, causing a variety of nontrivial phenomena such as circular dichiroism for chiral molecules, magnetic Skyrmions in chiral magnets and nonreciprocal carrier transport in chiral conductors. On the other hand, effect of chirality on superconducting transport has not been known. Here we report the nonreciprocity of superconductivity-unambiguous evidence of superconductivity reflecting chiral structure in which the forward and backward supercurrent flows are not equivalent because of inversion symmetry breaking. Such superconductivity is realized via ionic gating in individual chiral nanotubes of tungsten disulfide. The nonreciprocal signal is significantly enhanced in the superconducting state, being associated with unprecedented quantum Little-Parks oscillations originating from the interference of supercurrent along the circumference of the nanotube. The present results indicate that the nonreciprocity is a viable approach toward the superconductors with chiral or noncentrosymmetric structures.

Electrospray (ES) has attracted significant interest due to its advantages in generating uniform droplets and enabling controlled deposition. However, the complex interactions and droplet motion mechanisms between fluids and electric fields are still not well understood. Herein, this study presents a three-dimensional numerical model based on the volume of fluid and Lagrangian approaches to simulate the ES process in the pulsed jet mode. The model accurately captures the morphology and the atomization characteristics in the pulsed jet mode of ES. The effects of voltage and Reynolds number on the length of the non-atomized zone (including quasi-static Taylor cone, transition zone, and jet), diameter of the jet breakup, and atomization characteristics are discussed. Also, the mechanism of atomized droplets is revealed by analyzing the magnitudes of different types of forces imposing on the droplets in the electric field. The results indicate that higher Reynolds numbers lead to increased length of non-atomized zone and diameter of jet breakup, while the elevated voltages enhance atomization. Electric and Coulomb forces are, respectively, the dominant forces of forming the jet and expanding the atomization angle. Coulomb force increases the atomization angle, and electric field force increases the velocity of atomized droplets. Gravity and drag-force effects are relatively negligible throughout the atomization process. These findings contribute to a better understanding of the electrospray mechanisms and provide insights for optimizing electrospray applications. [ABSTRACT FROM AUTHOR]

UnlabelledInfluenza virus mRNA synthesis by the RNA-dependent RNA polymerase involves binding and cleavage of capped cellular mRNA by the PB2 and PA subunits, respectively, and extension of viral mRNA by PB1. However, the mechanism for such a dynamic process is unclear. Using high-throughput mutagenesis and sequencing analysis, we have not only generated a comprehensive functional map for the microdomains of individual subunits but also have revealed the PA linker to be critical for polymerase activity. This PA linker binds to PB1 and also forms ionic interactions with the PA C-terminal channel. Nearly all mutants with five-amino-acid insertions in the linker were nonviable. Our model further suggests that the PA linker plays an important role in the conformational changes that occur between stages that favor capped mRNA binding and cleavage and those associated with viral mRNA synthesis.ImportanceThe RNA-dependent RNA polymerase of influenza virus consists of the PB1, PB2, and PA subunits. By combining genome-wide mutagenesis analysis with the recently discovered crystal structure of the influenza polymerase heterotrimer, we generated a comprehensive functional map of the entire influenza polymerase complex. We identified the microdomains of individual subunits, including the catalytic domains, the interaction interfaces between subunits, and nine linkers interconnecting different domains. Interestingly, we found that mutants with five-amino-acid insertions in individual linkers were nonviable, suggesting the critical roles these linkers play in coordinating spatial relationships between the subunits. We further identified an extended PA linker that binds to PB1 and also forms ionic interactions with the PA C-terminal channel.

Background: Preclinical and clinical evidence indicates that proton pump inhibitors (PPIs) may indirectly diminish the microbiome diversity, thereby reducing the effectiveness of immune checkpoint inhibitors (ICIs). Conversely, recent publications have shown that PPIs could potentially enhance the response to ICIs. The precise mechanism through which PPIs modulate the ICIs remains unclear. In this study, we discovered a novel molecular function of PPIs in regulating immune invasion, specifically through inducing PD‐L1 translocation in various tumor cells. Methods: C57BL/6 mice subcutaneous transplantation model is used to verify the potential efficacy of PPIs and PD‐L1 antibody. Western blotting analysis and phosphorylated chip are used to verify the alteration of PD‐L1‐related pathways after being treated with PPIs. The related gene expression is performed by qRT‐PCR and luciferase reporter analysis. We also collected 60 clinical patients diagnosed with esophageal cancer or reflux esophagitis and then detected the expression of PD‐L1 in the tissue samples by immunohistochemistry. Results: We observed that the IC50 of tumor cells in response to PPIs was significantly higher than that of normal epithelial cells. PPIs significantly increased the expression of PD‐L1 on cell membrane at clinically relevant concentrations. Furthermore, pre‐treatment with PPIs appeared to synergize the efficiency of anti‐PD‐L1 antibodies in mouse models. However, PPI administration did not alter the transcription or total protein level of PD‐L1 in multiple tumor cells. Using a phosphorylated protein chip, we identified that PPIs enhanced the phosphorylation of GSK3β, then leading to PD‐L1 protein translocation to the cell membranes. The capacity of PPIs to upregulate PD‐L1 was negated following GSK3β knockout. Furthermore, our clinical data showed that the PPIs use resulted in increased PD‐L1 expression in esophageal cancer patients. Conclusion: We mainly address a significant and novel mechanism that the usage of PPIs could directly induce the expression of PD‐L1 by inducing GSK3β phosphorylation and facilitate primary tumor progression and metastasis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Prostate cancer (PCa) is the most common malignant tumor in the male genitourinary system. Once PCa has metastasized, it is very difficult to cure. The purpose of this study was to investigate the prognostic risk factor analysis of patients with different prostate- specific antigen (PSA) levels in distant metastatic PCa. At the same time, we construct effective models for predicting the survival rate of prostate cancer patients. PATIENTS AND METHODS: Data on prostate cancer patients with the presence of distant metastases were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. PCa patients with distant metastases were categorized into two groups based on PSA levels, one with PSA <20 ng/mL and the other with PSA ≥20 ng/mL. Univariate and multivariate COX regression analyses were used to identify independent factors affecting the prognosis of the patients. A nomogram was constructed using the independent prognostic factors, and the results were evaluated using calibration curves, timeROC curves, and Kaplan-Meier curves. RESULTS: In the PSA <20 ng/mL group, there were a total of 1,832 patients. COX regression analysis showed that age, marital status, N stage, grade, Gleason score, and medical household income inflation were independent prognostic factors for overall survival (OS) in patients. In addition, we found that age, marital status, N stage, bone metastasis, grade, and Gleason score were independent prognostic factors for cancer-specific survival (CSS) in patients. In the PSA ≥20 ng/mL group, there were a total of 5,314 patients. It was found that age, ethnicity, marital status, bone metastasis, first malignant primary indicator, grade, Gleason score, and medical household income inflation were patients' independent prognostic factors for OS. For CSS, we found that age, ethnicity, marital status, T stage, radiotherapy, bone metastasis, Gleason score, and Median household income inflation were independent prognostic factors. Constructing a nomogram can accurately predict the prognosis of this group of patients. CONCLUSIONS: We found different independent prognostic factors for different PSA levels in patients with distant metastatic PCa. A new nomogram was constructed to predict OS and CSS in patients, which helps in clinical-assisted decision-making. [ABSTRACT FROM AUTHOR]