Mandarin fish von Hippel-Lindau protein regulates the NF-κB signaling pathway via interaction with IκB to promote fish ranavirus replication

The von Hippel-Lindau tumor suppressor protein(VHL),an E3 ubiquitin ligase,functions as a critical regulator of the oxygen-sensing pathway for targeting hypoxia-inducible factors.Recent evidence suggests that mammalian VHL may also be critical to the NF-κB signaling pathway,although the specific molecular mechanisms remain unclear.Herein,the roles of mandarin fish(Siniperca chuatsi)VHL(scVHL)in the NF-κB signaling pathway and mandarin fish ranavirus(MRV)replication were explored.The transcription of scVHL was induced by immune stimulation and MRV infection,indicating a potential role in innate immunity.Dual-luciferase reporter gene assays and reverse transcription quantitative PCR(RT-qPCR)results demonstrated that scVHL evoked and positively regulated the NF-κB signaling pathway.Treatment with NF-κB signaling pathway inhibitors indicated that the role of scVHL may be mediated through scIKKα,scIKKβ,scIκBα,or scp65.Co-immunoprecipitation(Co-IP)analysis identified scIκBαas a novel target protein of scVHL.Moreover,scVHL targeted scIκBαto catalyze the formation of K63-linked polyubiquitin chains to activate the NF-κB signaling pathway.Following MRV infection,NF-κB signaling remained activated,which,in turn,promoted MRV replication.These findings suggest that scVHL not only positively regulates NF-κB but also significantly enhances MRV replication.This study reveals a novel function of scVHL in NF-κB signaling and viral infection in fish.

Exploring the effect of fingertip aero-haptic feedforward cues in directing eyes-free target acquisition in VR

Background The sense of touch plays a crucial role in interactive behavior within virtual spaces,particularly when visual attention is absent.Although haptic feedback has been widely used to compensate for the lack of visual cues,the use of tactile information as a predictive feedforward cue to guide hand movements remains unexplored and lacks theoretical understanding.Methods This study introduces a fingertip aero-haptic rendering method to investigate its effectiveness in directing hand movements during eyes-free spatial interactions.The wearable device incorporates a multichannel micro-airflow chamber to deliver adjustable tactile effects on the fingertips.Results The first study verified that tactile directional feedforward cues significantly improve user capabilities in eyes-free target acquisition and that users rely heavily on haptic indications rather than spatial memory to control their hands.A subsequent study examined the impact of enriched tactile feedforward cues on assisting users in determining precise target positions during eyes-free interactions,and assessed the required learning efforts.Conclusions The haptic feedforward effect holds great practical promise in eyeless design for virtual reality.We aim to integrate cognitive models and tactile feedforward cues in the future,and apply richer tactile feedforward information to alleviate users'perceptual deficiencies.

快速HE染色在周围型肺癌穿刺活检快速现场细胞学评价中的应用

背景与目的快速现场评价(rapid on-site evaluation,ROSE)是在活检术中同步实施的标本快速细胞学染色和评价技术。迪夫(Diff-Quik,DQ)染色是快速现场细胞学评价(cytological ROSE,C-ROSE)最常用的染色方法,但国内大部分病理医生不使用DQ染色进行现场细胞学判读,因此难以开展C-ROSE。本研究拟在周围型肺癌穿刺活检过程中分别使用快速苏木素-伊红(hematoxylin-eosin,HE)染色和DQ染色进行C-ROSE,评估快速HE染色在C-ROSE中的应用价值。方法对300例术前拟诊周围型肺癌患者实施胸部计算机断层扫描(computed tomography,CT)引导肺活检,随机分成两组且分别使用快速HE染色和DQ染色,进行C-ROSE判读,并对两种染色方法进行比较和评价。结果C-ROSE与组织病理诊断符合率为96.7%。快速HE染色的中位时间为160 s,而DQ染色为120 s,两组存在统计学差异(P<0.001)。但两组的肺活检时间、组织病理符合率、细胞学标本脱片率和严重不良反应发生率均无统计学差异(P>0.05)。结论在周围型肺癌活检过程中,两种染色方法均能满足C-ROSE要求,快速HE染色可应用于C-ROSE,且更符合国内临床需求,具有潜在的推广价值。

Mass spectrometry-based serum peptide profiling in hepatocellular carcinoma with bone metastasis

AIM: To investigate the potential of serum peptides as a diagnostic tool for hepatocellular carcinoma (HCC) with bone metastasis.

Simulation and visualization of the displacement between CO2 and formation fluids at pore-scale levels and its application to the recovery of shale gas

This article reports recent developments and advances in the simulation of the CO2-formation fluid displacement behaviour at the pore scale of subsurface porous media. Roughly, there are three effective visualization approaches to detect and observe the CO2-formation fluid displacement mechanism at the micro-scale, namely, magnetic resonance imaging, X-ray computed tomography and fabricated micromodels, but they are not capable of investigating the dis- placement process at the nano-scale. Though a lab-on-chip approach for the direct visualization of the fluid flow behaviour in nanoscale channels has been developed using an advanced epi-fluorescence microscopy method combined with a nanofluidic chip, it is still a qualitative analysis method. The lattice Boltzmann method （LBM） can simulate the CO2 displacement processes in a two-dimensional or three-dimensional （3D） pore structure, but until now, the CO2 displace- ment mechanisms had not been thoroughly investigated and the 3D pore structure of real rock had not been directly taken into account in the simulation of the CO2 displacement process. The status of research on the applications of CO2 displacement to enhance shale gas recovery is also analyzed in this paper. The coupling of molecular dynamics and LBM in tandem is proposed to simulate the CO2-shale gas displacement process based on the 3D digital model of shale obtained from focused ion beams and scanning electron microscopy.

Application of Newcastle disease virus in the treatment of colorectal cancer

Colorectal cancer (CRC) is one of the main reasons of tumor-related deaths worldwide.At present,the main treatment is surgery,but the results are unsatisfactory,and the prognosis is poor.The majority of patients die due to liver or lung metastasis or recurrence.In recent years,great progress has been made in the field of tumor gene therapy,providing a new treatment for combating CRC.As oncolytic viruses selectively replicate almost exclusively in the cytoplasm of tumor cells and do not require integration into the host genome,they are safer,more effective and more attractive as oncolytic agents.Newcastle disease virus (NDV) is a natural RNA oncolytic virus.After NDV selectively infects tumor cells,the immune response induced by NDV’s envelope protein and intracellular factors can effectively kill the tumor without affecting normal cells.Reverse genetic techniques make NDV a vector for gene therapy.Arming the virus by inserting various exogenous genes or using NDV in combination with immunotherapy can also improve the anti-CRC capacity of NDV,and good results have been achieved in animal models and clinical treatment trials.This article reviews the molecular biological characteristics and oncolytic mechanism of NDV and discusses in vitro and in vivo experiments on NDV anti-CRC capacity and clinical treatment.In conclusion,NDV is an excellent candidate for cancer treatment,but more preclinical studies and clinical trials are needed to ensure its safety and efficacy.

Targeted Antimicrobial Therapy Against Streptococcus mutans Establishes Protective Non-cariogenic Oral Biofilms and Reduces Subsequent Infection

Aim Dental biofilms are complex communities composed largely of harmless bacteria. Certain pathogenic species including Streptococcus mutans （S. mutans） can become predominant when host factors such as dietary sucrose intake imbalance the biofilm ecology. Current approaches to control S. mutans infection are not pathogen-specific and eliminate the entire oral community along with any protective benefits provided. Here, we tested the hypothesis that removal of S. mutans from the oral community through targeted antimicrobial therapy achieves protection against subsequent S. mutans colonization. Methodology Controlled amounts of S. mutans were mixed with S. mutans-free saliva, grown into biofilms and visualized by antibody staining and cfu quantization. Two specifically-targeted antimicrobial peptides （STAMPs） against S. mutans were tested for their ability to reduce S. mutans biofilm incorporation upon treatment of the inocula. The resulting biofilms were also evaluated for their ability to resist subsequent exogenous S. mutans colonization. Results S. mutans colonization was considerably reduced （9 ± 0.4 fold reduction, P=0.01） when the surface was preoccupied with saliva-derived biofilms. Furthermore, treatment with S. mutans-specific STAMPs yielded S. mutans-deficient biofilms with significant protection against further S. mutans colonization （5 minutes treatment： 38 ± 13 fold reduction P=0.01; 16 hours treatment： 96 ± 28 fold reduction P=0.07）. Conclusion S. mutans infection is reduced by the pre- sence of existing biofilms. Thus maintaining a healthy or ＂normal＂ biofilm through targeted antimicrobial therapy （such as the STAMPs） could represent an effective strategy for the treatment and prevention of S. mutans colonization in the oral cavity and caries progression.

Amyloid cross-seeding between Ab and hIAPP in relation to the pathogenesis of Alzheimer and type 2 diabetes

Amyloid cross-seeding of different amyloid proteins is considered as a highly possible mechanism for exacerbating the transmissible pathogenesis of protein misfolding disease(PMDs)and for explaining a molecular link between different PMDs,including Alzheimer disease(AD)and type 2 diabetes(T2D),AD and Parkinson disease(PD),and AD and prion disease.Among them,AD and T2D are the most prevalent PMDs,affecting millions of people globally,while Ab and hIAPP are the causative peptides responsible for AD and T2D,respectively.Increasing clinical and epidemiological evidences lead to a hypothesis that the cross-seeding of Ab and hIAPP is more biologically responsible for a pathological link between AD and T2D.In this review,we particularly focus on(i)the most recent and important findings of amyloid cross-seeding between Ab and hIAPP from in vitro,in vivo,and in silico studies,(ii)a mechanistic role of structural compatibility and sequence similarity of amyloid proteins(beyond Ab and hIAPP)in amyloid cross-seeding,and(iii)several current challenges and future research directions in this lessstudied field.Review of amyloid cross-seeding hopefully provides some mechanistic understanding of amyloidogenesis and inspires more efforts for the better design of next-generation drugs/strategies to treat different PMDs simultaneously.

Development and evaluation of a safe and effective sugar-free herbal lollipop that kills cavity-causing bacteria

Dental caries （tooth decay） is caused by a specific group of cariogenic bacteria, like Streptococcus mutans, which convert dietary sugars into acids that dissolve the mineraI in tooth structure. Killing cariogenic bacteria is an effective way to control or prevent tooth decay. In a previous study, we discovered a novel compound （Glycyrrhizol A）, from the extraction of licorice roots, with strong antimicrobial activity against cariogenic bacteria. In the current study, we developed a method to produce these specific herbal extracts in large quantities, and then used these extracts to develop a sugar-free lollipop that effectively kills cariogenic bacteria like Streptococcus mutans. Further studies showed that these sugar-free lollipops are safe and their antimicrobial activity is stable. Two pilot human studies indicate that a brief application of these lollipops （twice a day for ten days） led to a marked reduction of cariogenic bacteria in oral cavity among most human subjects tested. This herbal lollipop could be a novel tool to promote oral health through functional foods.

Application of photodynamic therapy in cancer: challenges and advancements

Although great achievements have been made in the past decades in medicine,cancer remains a worldwide public health issue.Surgery is usually accompanied by shortcomings such as residual lesions and poor treatment effects,and the successive appearance of other treatment methods,such as radiotherapy and chemotherapy,has not changed the postoperative recurrence rate,toxicity,and side effects.However,the advent of photodynamic therapy has greatly improved this situation.Photodynamic therapy is an emerging tumor diagnosis and treatment technology with good application prospects,photodynamic therapy uses a specific wavelength of light to excite a photosensitizer to generate reactive oxygen species,damage tumor blood vessels and promote tumor cell apoptosis,exerting an anti-tumor effect.Photodynamic therapy has become a new clinical anti-tumor therapy due to its clear efficacy,few side effects,and easy use in combination with other therapies.In this review,we summarized the main mechanism,current challenges,and advancements of photodynamic therapy.

Interface-enhanced thermoelectric output power in CrN/SrTiO_(3-x) heterostructure

Thermoelectric devices enable direct conversion between thermal and electrical energy.Recent studies have indicated that the thin film/substrate heterostructure is effective in achieving high thermoelectric performance via decoupling the Seebeck coefficient and electrical conductivity otherwise adversely inter-dependent in homogenous bulk materials.However,the mechanism underlying the thin film/substrate heterostructure thermoelectricity remains unclear.In addition,the power output of the thin film/substrate heterostructure is limited to the nanowatt scale to date,falling short of the practical application requirement.Here,we fabricated the CrN/SrTiO_(3-x) heterostructures with high thermoelectric output power and outstanding thermal stability.By varying the CrN film thickness and the reduction degree of CrN/SrTiO_(3-x) substrate,the optimized power output and the power density have respectively reached 276μWand 10^(8) mW/cm^(2) for the 30 nm CrN film on a highly reduced surface of CrN/SrTiO_(3-x) under a temperature difference of 300 K.The performance enhancement is attributed to the CrN/CrN/SrTiO_(3-x) heterointerface,corroborated by the band bending as revealed by the scanning Kelvin probe microscopy.These results will stimulate further research efforts towards interface thermoelectrics.

Bluetooth-based authentication system for ambient intelligence

According to the requirement of natural human-computer interaction for Ambient Intelligence （Aml）, a Bluetoothbased authentication technique is provided. An authentication network combining advantages of Bluetooth ad hoc network with the Ethernet is introduced first in detail. Then we propose a Bluetooth badge for storing the user＇s identification information. Finally, the authentication system based on Bluetooth badge and authentication network is introduced. It is demonstrated experimentally that the Bluetooth-based authentication technique can authenticate the user automatically.

Effect of a disposable endoscope precleaning kit in the cleaning procedure of gastrointestinal endoscope:A multi-center observational study

BACKGROUND Precleaning is a key step in endoscopic reprocessing.AIM To develop an effective and economic endoscope cleaning method by using a disposable endoscope bedside precleaning kit.METHODS Altogether,228 used gastrointestinal endoscopes were selected from five high-volume endoscopy units and precleaned by a traditional precleaning bucket(group T)or a disposable endoscope bedside precleaning kit(group D).Each group was further subdivided based on the replacement frequency of the cleaning solution,which was replaced every time in subgroups T1 and D1 and every several times in subgroups Ts and Ds.The adenosine triphosphate(ATP)level and residual proteins were measured three times:Before and after precleaning and after manual cleaning.RESULTS After precleaning,the precleaning kit significantly reduced the ATP levels(P=0.034)and has a more stable ATP clearance rate than the traditional precleaning bucket.The precleaning kit also saved a quarter of the cost of enzymatic detergent used during the precleaning process.After manual cleaning,the ATP levels were also significantly lower in the precleaning kit group than in the traditional precleaning bucket group(P<0.05).Meanwhile,the number of uses of the cleaning solution(up to four times)has no significant impact on the cleaning effect(P>0.05).CONCLUSION Considering its economic cost and cleaning effect,the use of a disposable endoscope bedside precleaning kit can be an optimal option in the precleaning stage with the cleaning solution being replaced several times in the manual cleaning stage.

Challenges and response to pandemics as seen in a One Health perspective

The global pandemic caused by the coronavirus disease 2019 not only exposed the fragility of global preparedness and response to public health emergence,but also illustrated the fragmentation and gaps of research and development ecosystem.This emphasizes the need for planned actions against the potentiality of new pandemics and requires research to better understand how viruses bridge the animal/human divide making human-to-human transmission of new diseases possible.Major challenges to response to new epidemics under the current health framework reside in the so called 4-CC approach that focuses on Concept,Communication,Coherence,and Continuity.There is a need to also add a One Health perspective with emphasis on governance,surveillance,capacity building and multi-disciplinary research to achieve a holistic and better integrated system.Using a regulatory framework to equip professionals might facilitate the function of a multi-sector approach that recognizes the value of their mandates and a One Health approach in their work.Collaborative,multisectoral actions under the global regulations and guidance would make evidence-based One Health approaches sustainable and accessible to everyone.

Emergency risk management for landslide dam breaks in 2018 on the Yangtze River,China

In October and November of 2018,the upper reach of the Yangtze River was blocked twice by landslide dams.A large landslide dam on a major river can impound a huge amount of water and trigger catastrophic flooding once it fails,imposing great risk to the downstream communities.Considering the chain of large dams and densely populated cities along the river,there is an urgent need to improve the system resilience of the Yangtze River to the landslide dam break hazard.This study presents a basin-scale emergency risk management framework based on an overtopping-erosion based dam failure model and a 1-D flood routing analysis model.Basin-wide inundation and detailed flood risk analyses are carried out considering engineering risk mitigation measures,which will facilitate the decision-making on future emergency risk mitigation plans.The proposed framework is applied to the landslide dam on the Yangtze River in November 2018.Results show that excavating a 15 m-depth diversion channel could effectively mitigate the flood risk of downstream areas.Further mitigation measures,including evacuation,removal of obstacles in the river,and preparation of certain intercept capacity in downstream reservoirs,are suggested based on the hazard chain risk analysis.The mitigation results in the case prove the effectiveness of the proposed framework.The incorporation of open-access global databases enables the application of the framework to any large river basin worldwide.

Targeting of AUF1 to vascular endothelial cells as a novel anti-aging therapy

Background Inhibition of aging of vascular endothelial cells （VECs） may delay aging and prolong life. The goal of this study was to prepare anti-CD31 monoclonal antibody conjugated PEG-modified liposomes containing the AU-rich region connecting factor 1 （AUF1） gene （CD31-PILs-AUF1） and to explore the effects of targeting CD31-PILs-AUF1 to aging VECs. Methods The mean particle sizes of various PEGylated immunoliposomes （PILs） were measured using a Zetasizer Nano ZS. Gel retardation assay was used to confirm whether PILs had encapsulated the AUF1 plasmid successfully. Fluorescence microscopy and flow cytometry were used to quantify binding of CD31-PILs-AUF1 to target cells. Flow cytometry was also used to analyze the cell cycles of aging bEnd3 cells treated with CD31-PILs-AUF1. We also developed an aging mouse model by treating mice with D-galactose. Enzyme-linked immunosorbent assay （ELISA） was used to evaluate the levels of interleuldn-6 （IL-6） and tumor necrosis factor-or （TNF-ct）. The malondialdehyde （MDA） and the superoxide dismutase （SOD） levels were detected by commercial kits. Hematoxylin-eosin （HE） staining was used to determine whether treatment with CD31-PILs-AUF 1 was toxic to the mice. Results CD31-PILs-AUF 1 specifically could targeted bEnd3 VECs and increased the percentage of cells in the S and G2/M phases of aging bEnd3 cells. ELISA showed that content of the IL-6 and TNF-ct decreased in CD31-PILs-AUF1 group. The level of SOD increased, whereas MDA decreased in the CD31-PILs-AUF1 group. Additionally, CD31-PILs-AUF 1 was not toxic to the mice. Conclusion CD31-PILs-AUF 1 targets VECs and may delay their senescence.

Pulmonary arterial hyper-tension in a patient with hereditary hemorrhagic telangiectasia and family gene analysis:A case report

BACKGROUND Hereditary hemorrhagic telangiectasia(HHT)is a rare autosomal dominant genetic disease.Very few patients suffering from HHT present with associated pulmonary arterial hypertension(PAH),which may result in a poor prognosis.Here,we report a case of HHT with PAH.The patient’s clinical manifestations and treatment as well as genetic analysis of family members are reviewed,in order to raise awareness of this multimorbidity.CASE SUMMARY A 45-year-old Chinese woman was admitted to the hospital to address a complaint of intermittent shortness of breath,which had lasted over the past 2 years.She also had a 30-year history of recurrent epistaxis and 5-year history of anemia.She reported that the shortness of breath had aggravated gradually over the 2 years.Physical examination discovered anemia and detected gallop rhythm in the precordium.Chest computerized tomography and cardiac ultrasound demonstrated PAH and hepatic arteriovenous malformation.The formal clinical diagnosis was HHT combined with PAH.The patient was treated with ambrisentan and her condition improved for a time.She died half a year after the diagnosis.Genetic testing revealed the patient and some family members to carry an activin A receptor-like type 1 mutation(c.1232G>A,p.Arg411Gln);the family was thus identified as an HHT family.CONCLUSION We report a novel gene mutation(c.1232G>A,p.Arg411Gln)in a Chinese HHT patient with PAH.

Massive bleeding from a gastric artery pseudoaneurysm in hepatocellular carcinoma treated with atezolizumab plus bevacizumab: A case report

BACKGROUND The combination of atezolizumab(ATZ)and bevacizumab(BVZ)was approved as first-line systemic therapy for advanced hepatocellular carcinoma(HCC)owing to its superior rates of response and patient survival.However,ATZ+BVZ is associated with increased risk of upper gastrointestinal(GI)bleeding,including arterial bleeding,which is rare and potentially fatal.We present a case of massive upper GI bleeding from a gastric pseudoaneurysm in a patient with advanced HCC who had been treated with ATZ+BVZ.CASE SUMMARY A 67-year-old man presented with severe upper GI bleeding after atezolizumab(ATZ)+bevacizumab(BVZ)therapy for HCC.Endoscopy failed to detect the bleeding site.Digital subtraction angiography revealed a gastric artery pseudoaneurysm and contrast extravasation from the inferior splenic artery and a branch of the left gastric artery.Successful hemostasis was achieved with embolization.CONCLUSION HCC patients who have been treated with ATZ+BVZ should be followed for 3 to 6 mo to monitor for development of massive GI bleeding.Diagnosis may require angiography.Embolization is an effective treatment.

Effectiveness of an Indoor Air Pollution (IAP) Intervention on Reducing IAP and Improving Women’s Health Status in Rural Areas of Gansu Province, China

Given the deleterious health effects associated with indoor air pollution (IAP), this study was conducted to evaluate an IAP intervention in rural areas in Gansu, one of the poorest provinces of China. We selected 371 rural households to take part in intervention measures including stove improvement and health education. Eight of 371 households were selected to conduct IAP sampling. Four hundred and thirteen women in these households completed a questionnaire and 49 women took part in lung function tests. After the intervention, PM4 levels reduced from 455 μg/m3 to 200 μg/m3 and CO reduced from 3.40 ppm to 2.90 ppm in indoor air. The percentage of predicted value of FEV1 and FVC improved to some degree after the intervention, but all the parameters of lung function assessment did not show a significant change. Prevalence rates of several symptoms associated with IAP significantly declined in the study population, compared with baseline levels. Intervention measures combining stove improvement with health education were effective in reducing IAP levels. Women’s health status, including eye and respiratory symptoms, also showed improvement. However, the effect on lung function was not apparent and warranted additional follow-up. Similarly, evaluation of the long term effects of the IAP intervention will require future studies.

Acetalization strategy in biomass valorization: a review

Acetalization represents an appealing approach for the valorization of biobased platform molecules into valuable chemicals and fuels.Typically,it serves as both a synthesis tool for renewable cyclic acetals and a protection strategy to improve selectivity in biomass conversion.This contribution provides an overview on the application of the acetalization strategy in biomass valorization including synthesis of cyclic acetal fuel additives from the acetalization of biobased furanic compounds with biogenic ethylene glycol/glycerol and acetalization as a protection approach to improve product selectivity in biomass valorization.The latest progresses in the development of catalytic systems for the acetalization of biobased furanic compounds and biogenic ethylene glycol/glycerol are systematically summarized and discussed,with an emphasis on the reaction pathway,relationship between catalyst structures and their performance,and relevant catalytic mechanism.Moreover,the application of the acetalization strategy for protecting carbonyl groups/diol structure functionalities to improve the target products'selectivity in lignin depolymerization,5-hydroxymethylfurfural oxidation,sorbitol dehydration,and xylose hydrogenation is also highlighted.Eventually,the prospects and challenges in the synthesis of cyclic acetal fuel additives as well as applying acetalization as a protection strategy in biomass valorization are outlined.