Host MOV10 is induced to restrict herpes simplex virus 1 lytic infection by promoting type I interferon response.

Moloney leukemia virus 10 protein (MOV10) is an interferon (IFN)-inducible RNA helicase implicated in antiviral activity against RNA viruses, yet its role in herpesvirus infection has not been investigated. After corneal inoculation of mice with herpes simplex virus 1 (HSV-1), we observed strong upregulation of both MOV10 mRNA and protein in acutely infected mouse trigeminal ganglia. MOV10 suppressed HSV-1 replication in both neuronal and non-neuronal cells, and this suppression required the N-terminus, but not C-terminal helicase domain of MOV10. MOV10 repressed expression of the viral gene ICP0 in transfected cells, but suppressed HSV-1 replication independently of ICP0. MOV10 increased expression of type I IFN in HSV-1 infected cells with little effect on IFN downstream signaling. Treating the cells with IFN-α or an inhibitor of the IFN receptor eliminated MOV10 suppression of HSV-1 replication. MOV10 enhanced IFN production stimulated by cytoplasmic RNA rather than DNA. IKKε co-immunoprecipitated with MOV10 and was required for MOV10 restriction of HSV-1 replication. Mass spectrometry identified ICP27 as a viral protein interacting with MOV10. Co-immunoprecipitation results suggested that this interaction depended on the RGG box of ICP27 and both termini of MOV10. Overexpressed ICP27, but not its RGG-Box deletion mutant, rendered MOV10 unable to regulate HSV-1 replication and type I IFN production. In summary, MOV10 is induced to restrict HSV-1 lytic infection by promoting the type I IFN response through an IKKε-mediated RNA sensing pathway, and its activity is potentially antagonized by ICP27 in an RGG box dependent manner.

Heisenberg-limited spin squeezing in a hybrid system with silicon-vacancy centers.

In this paper, we investigate the spin squeezing in a hybrid quantum system consisting of a Silicon-Vacancy (SiV) center ensemble coupled to a diamond acoustic waveguide via the strain interaction. Two sets of non-overlapping driving fields, each contains two time-dependent microwave fields, are applied to this hybrid system. By modulating these fields, the one-axis twist (OAT) interaction and two-axis two-spin (TATS) interaction can be independently realized. In the latter case the squeezing parameter scales to spin number as ξ R2∼1.61N -0.64 with the consideration of dissipation, which is very close to the Heisenberg limit. Furthermore, this hybrid system allows for the study of spin squeezing generated by the simultaneous presence of OAT and TATS interactions, which reveals sensitivity to the parity of the number of spins Ntot, whether it is even or odd. Our scheme enriches the approach for generating Heisenberg-limited spin squeezing in spin-phonon hybrid systems and offers the possibility for future applications in quantum information processing.

Quantum Phase Transitions in Optomechanical Systems.

In this Letter, we investigate the ground state properties of an optomechanical system consisting of a coupled cavity and mechanical modes. An exact solution is given when the ratio η between the cavity and mechanical frequencies tends to infinity. This solution reveals a coherent photon occupation in the ground state by breaking continuous or discrete symmetries, exhibiting an equilibrium quantum phase transition (QPT). In the U(1)-broken phase, an unstable Goldstone mode can be excited. In the model featuring Z_{2} symmetry, we discover the mutually (in the finite η) or unidirectionally (in η→∞) dependent relation between the squeezed vacuum of the cavity and mechanical modes. In particular, when the cavity is driven by a squeezed field along the required squeezing parameter, it enables modifying the region of Z_{2}-broken phase and significantly reducing the coupling strength to reach QPTs. Furthermore, by coupling atoms to the cavity mode, the hybrid system can undergo a QPT at a hybrid critical point, which is cooperatively determined by the optomechanical and light-atom systems. These results suggest that this optomechanical system complements other phase transition models for exploring novel critical phenomena.

Human umbilical cord mesenchymal stem cells alleviate fatty liver ischemia-reperfusion injury by activating autophagy through upregulation of IFNγ.

Liver ischemia-reperfusion injury (IRI) is an important factor affecting the prognosis of liver transplantation, and extended criteria donors (e.g., steatosis donor livers) are considered to be more sensitive to ischemia-reperfusion injury in liver transplantation. Currently, the application of human umbilical cord mesenchymal stem cells (hMSCs) has great promise in the treatment of various injuries in the liver. This study aimed to investigate the therapeutic role and mechanism of hMSCs in fatty liver IRI. After more than 8 weeks of high-fat chow feeding, we constructed a fatty liver mouse model and established ischemic injury of about 70% of the liver. Six hours after IRI, liver injury was significantly alleviated in hMSCs-treated mice, and the expression levels of liver enzyme, inflammatory factor TNF-α, and apoptotic proteins were significantly lower than those of the control group, which were also significant in pathological sections. Transcriptomics analysis showed that IFNγ was significantly upregulated in the hMSCs group. Mechanistically, IFNγ, which activates the MAPK pathway, is a potent agonist that promotes the occurrence of autophagy in hepatocytes to exert a protective function, which was confirmed by in vitro experiments. In summary, hMSCs treatment could slow down IRI in fatty liver by activating autophagy through upregulation of IFNγ, and this effect was partly direct.

Animal models of hepatitis E infection: Advances and challenges.

Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis worldwide. Although most of HEV infections are asymptomatic, some patients will develop the symptoms, especially pregnant women, the elderly, and patients with preexisting liver diseases, who often experience anorexia, nausea, vomiting, malaise, abdominal pain, and jaundice. HEV infection may become chronic in immunosuppressed individuals. In addition, HEV infection can also cause several extrahepatic manifestations. HEV exists in a wide range of hosts in nature and can be transmitted across species. Hence, animals susceptible to HEV can be used as models. The establishment of animal models is of great significance for studying HEV transmission, clinical symptoms, extrahepatic manifestations, and therapeutic strategies, which will help us understand the pathogenesis, prevention, and treatment of hepatitis E. This review summarized the animal models of HEV, including pigs, monkeys, rabbits, mice, rats, and other animals. For each animal species, we provided a concise summary of the HEV genotypes that they can be infected with, the cross-species transmission pathways, as well as their role in studying extrahepatic manifestations, prevention, and treatment of HEV infection. The advantages and disadvantages of these animal models were also emphasized. This review offers new perspectives to enhance the current understanding of the research landscape surrounding HEV animal models.

Chlorogenic acid alleviates renal fibrosis by reducing lipid accumulation in diabetic kidney disease through suppressing the Notch1 and Stat3 signaling pathway.

AIMS: Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study was to investigate the effect and mechanism of chlorogenic acid (CA) on reducing renal lipid accumulation and improving DKD renal fibrosis. METHODS: This study evaluated the effects of CA on renal fibrosis, lipid deposition and lipid metabolism by constructing in vitro and in vivo models of DKD, and detected the improvement of Notch1 and Stat3 signaling pathways. Molecular docking was used to predict the binding between CA and the extracellular domain NRR1 of Notch1 protein. RESULTS: In vitro studies have shown that CA decreased the expression of Fibronectin, α-smooth muscle actin (α-SMA), p-smad3/smad3, alleviated lipid deposition, promoted the expression of carnitine palmitoyl transferase 1 A (CPT1A), and inhibited the expression of cholesterol regulatory element binding protein 1c (SREBP1c). The expression of Notch1, Cleaved Notch1, Hes1, and p-stat3/stat3 were inhibited. These results suggested that CA might reduce intercellular lipid deposition in human kidney cells (HK2) by inhibiting Notch1 and stat3 signaling pathways, thereby improving fibrosis. Further, in vivo studies demonstrated that CA improved renal fibrosis and renal lipid deposition in DKD mice by inhibiting Notch1 and stat3 signaling pathways. Finally, molecular docking experiments showed that the binding energy of CA and NRR1 was -6.6 kcal/mol, which preliminarily predicted the possible action of CA on Notch1 extracellular domain NRR1. CONCLUSION: CA reduces renal lipid accumulation and improves DKD renal fibrosis by inhibiting Notch1 and stat3 signaling pathways.

Serum extracellular vesicle-derived ASS1 is a promising predictor for the occurrence of HEV-ALF.

Development of biomarkers for predicting the occurrence of hepatitis E virus related-acute liver failure (HEV-ALF) is conducive to prevention and early intervention. Serum samples from 250 HEV-ALF patients, 250 patients with acute hepatitis E (AHE) and 250 health controls (HCs) were collected. We assessed the predictive ability of extracellular vesicle (EV)-derived argininosuccinate synthase 1 (ASS1) levels for HEV-ALF occurrence. Serum EVs were successfully isolated. EV-derived ASS1 levels in the HEV-ALF patients were significantly higher than those in the AHE patients and HCs. In HEV-ALF patients, EV-derived ASS1 levels were positively correlated with the number of failed organs and disease progression. The logistical regression showed that EV-derived ASS1 level is an independent risk factor for HEV-ALF, and orthogonal partial least squares discriminant analysis (OPLS-DA) also suggested that EV-derived ASS1 level has high predictive capability. Besides, the area under the curve (AUC) of EV-derived ASS1 level to predict HEV-ALF occurrence was 0.728 (0.684-0.772) with the sensitivity and specificity being 72.80% and 64.80%, which had a high decision-making ability. Furthermore, there existed no significant difference between the age ≥60 and age <60 groups in EV-derived ASS1 levels. Serum EV-derived ASS1 level is a promising predictor for the occurrence of HEV-ALF.

Universal Time-Dependent Control Scheme for Realizing Arbitrary Linear Bosonic Transformations.

We study the implementation of arbitrary excitation-conserving linear transformations between two sets of N stationary bosonic modes, which are connected through a photonic quantum channel. By controlling the individual couplings between the modes and the channel, an initial N-partite quantum state in register A can be released as a multiphoton wave packet and, successively, be reabsorbed in register B. Here we prove that there exists a set of control pulses that implement this transfer with arbitrarily high fidelity and, simultaneously, realize a prespecified N×N unitary transformation between the two sets of modes. Moreover, we provide a numerical algorithm for constructing these control pulses and discuss the scaling and robustness of this protocol in terms of several illustrative examples. By being purely control-based and not relying on any adaptations of the underlying hardware, the presented scheme is extremely flexible and can find widespread applications, for example, for boson-sampling experiments, multiqubit state transfer protocols, or in continuous-variable quantum computing architectures.

Radiomics in the diagnosis and treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumor. At present, early diagnosis of HCC is difficult and therapeutic methods are limited. Radiomics can achieve accurate quantitative evaluation of the lesions without invasion, and has important value in the diagnosis and treatment of HCC. Radiomics features can predict the development of cancer in patients, serve as the basis for risk stratification of HCC patients, and help clinicians distinguish similar diseases, thus improving the diagnostic accuracy. Furthermore, the prediction of the treatment outcomes helps determine the treatment plan. Radiomics is also helpful in predicting the HCC recurrence, disease-free survival and overall survival. This review summarized the role of radiomics in the diagnosis, treatment and prognosis of HCC.

Factors affecting acceptance of organ donation in mainland China: A national cross-sectional study.

AIMS AND OBJECTIVES: To explore the acceptances and associated influences of organ donation in mainland China. BACKGROUND: The shortage of organ donors has limited the development of organ transplantation in China. It is important to recognise the target population who has high intention to donate their organs may change the status. DESIGN: We conducted a cross-sectional, multi-stage sampling study collected demographic data and individuals' willingness to accept organ donation. METHODS: A stepwise linear regression analysis was adopted to evaluate the factors related to the attitudes toward organ donation. RESULTS: We collected 11,031 valid samples for the survey. The willingness to donate organs among Chinese residents averaged 56.93 points. To be specific, males (ß = -.03), religious believers (ß = -.01) and parents with a different number of children (all: ß = -.04) are less willing to donate their organs. Respondents who live in an urban area (ß = .03), have higher education level (High school or junior college ß = .04, Bachelor degree or above ß = .09), feel anxious (mild, moderate ß = .02), feel pressured (moderate, severe ß = .08), have higher scores of the Short-Form Health Literacy Instrument (HLS-SF12) (ß = .31), The Self-Management Scale (SHMS) (ß = .16), EuroQol Five Dimensions Questionnaire (EQ-5D) (ß = .04) and EuroQol Visual Analogue Scale (EQ-VAS) (ß = .24), are more positive to donate. CONCLUSIONS: This study firstly discusses the public acceptance of organ donation through a nationwide sample around China. In this study, we discovered that Chinese residents' acceptance level of organ donation and that gender, house, anxiety, pressure, social support and health literacy were the main influencing factors on residents' attitudes. RELEVANCE TO CLINICAL PRACTICE: To figure out the Chinese public acceptance and its influencing factors of organ donation can help nurse transplant coordinators to recognise the target population and the obstacles of organ donation. PATIENT OR PUBLIC CONTRIBUTION: At the phase of collecting data, participants were recruited to fill the questionnaires.

Sinomenine Hydrochloride Can Ameliorate Benign Prostatic Hyperplasia by Lowering the 5α-Reductase 2 Level and Regulating the Balance between the Proliferation and Apoptosis of Cells.

Benign prostatic hyperplasia (BPH) is a chronic disease that affects the quality of life of older males. Sinomenine hydrochloride (SIN) is the major bioactive alkaloid isolated from the roots of the traditional Chinese medicinal plant Sinomenium acutum Rehderett Wilson. We wondered if the SIN administration exerted a regulatory effect on BPH and its potential mechanism of action. Mice with testosterone propionate-induced BPH subjected to bilateral orchiectomy were employed for in vivo experiments. A human BPH cell line (BPH-1) was employed for in vitro experiments. SIN administration inhibited the proliferation of BPH-1 cells (p < 0.05) by regulating the expression of androgen-related proteins (steroid 5-alpha reductase 2 (SRD5A2), androgen receptors, prostate-specific antigen), apoptosis-related proteins (B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax)) and proliferation-related proteins (proliferating cell nuclear antigen (PCNA), mammalian target of rapamycin, inducible nitric oxide synthase) in vitro. SIN administration decreased the prostate-gland weight coefficient (p < 0.05) and improved the histological status of mice suffering from BPH. The regulatory effects of SIN administration on SRD5A2, an apoptosis-related protein (Bcl-2), and proliferation-related proteins (PCNA, matrix metalloproteinase-2) were consistent with in vitro data. SIN exerted a therapeutic effect against BPH probably related to lowering the SRD5A2 level and regulating the balance between the proliferation and apoptosis of cells. Our results provide an important theoretical basis for the development of plant medicines for BPH therapy.

The diagnostic and prognostic value of serum exosome-derived carbamoyl phosphate synthase 1 in HEV-related acute liver failure patients.

Early diagnosis and prognosis evaluation are of great significance to hepatitis E virus (HEV)-related acute liver failure (HEV-ALF) patients. We collected serum samples from 200 health controls (HCs), 200 patients with acute hepatitis E (AHE), and 200 HEV-ALF patients to evaluate serum exosome-derived carbamoyl phosphate synthase 1 (CPS1) levels and determine its diagnostic and prognostic value. The exosome-derived CPS1 levels in the HEV-ALF group were significantly higher than those in the AHE and HCs groups. The AUC of exosome-derived CPS1 to predict the occurrence of HEV-ALF was 0.850 (0.811-0.883). Both logistical regression and orthogonal partial least squares discriminant analysis (OPLS-DA) showed that exosome-derived CPS1 is an independent risk factor for HEV-ALF. The exosome-derived CPS1 levels were positively correlated with organ failure and the outcomes in HEV-ALF patients. The exosome-derived CPS1 levels in the worsening group were significantly higher than those in the fluctuating and the improving groups. The AUC of serum exosome-derived CPS1 to predict 30-day mortality was 0.829 (0.770-0.879), which was significantly greater than that of the Child-Pugh, KCH, and MELD models. The level of serum exosome-derived CPS1 might serve as a promising diagnostic and prognostic biomarker for HEV-ALF patients, which may provide better guidance for the diagnosis, prognosis, and treatment of HEV-ALF patients.

Deterministic generation of entanglement states between Silicon-Vacancy centers via acoustic modes.

We propose a scheme to entangle Silicon-Vacancy (SiV) centers embedded in a diamond acoustic waveguide. These SiV centers interact with acoustic modes of the waveguide via strain-induced coupling. Through Morris-Shore transformation, the Hilbert space of this hybrid quantum system can be factorized into a closed subspace in which we can deterministically realize the symmetrical Dicke states between distant SiV centers with high fidelity. In addition, the generation of entangled Dicke states can be controlled by manipulating the strength and frequency of the driving field applied on SiV centers. This protocol provides a promising way to prepare multipartite entanglement in spin-phonon hybrid systems and could have broad applications for future quantum technologies.

FAEE exerts a protective effect against osteoporosis by regulating the MAPK signalling pathway.

CONTEXT: Ferulic acid ethyl ester (FAEE) is abundant in Ligusticum chuanxiong Hort. (Apiaceae) and grains, and possesses diverse biological activities; but the effects of FAEE on osteoporosis has not been reported. OBJECTIVE: This study investigated whether FAEE can attenuate osteoclastogenesis and relieve ovariectomy-induced osteoporosis via attenuating mitogen-activated protein kinase (MAPK). MATERIALS AND METHODS: We stimulated RAW 264.7 cells with receptor activator of NF-κB ligand (RANKL) followed by FAEE. The roles of FAEE in osteoclast production and osteogenic resorption of mature osteoclasts were evaluated by tartrate resistant acid phosphatase (TRAP) staining, expression of osteoclast-specific genes, proteins and MAPK. Ovariectomized (OVX) female Sprague-Dawley rats were administered FAEE (20 mg/kg/day) for 12 weeks to explore its potential in vivo, and then histology was undertaken in combination with cytokines analyses. RESULTS: FAEE suppressed RANKL-induced osteoclast formation (96 ± 0.88 vs. 15 ± 1.68) by suppressing the expression of osteoclast-specific genes, proteins and MAPK signalling pathway related proteins (p-ERK/ERK, p-JNK/JNK and p-P38/P38) in vitro. In addition, OVX rats exposed to FAEE maintained their normal calcium (Ca) (2.72 ± 0.02 vs. 2.63 ± 0.03, p < 0.05) balance, increased oestradiol levels (498.3 ± 9.43 vs. 398.7 ± 22.06, p < 0.05), simultaneously reduced levels of bone mineral density (BMD) (0.159 ± 0.0016 vs. 0.153 ± 0.0025, p < 0.05) and bone mineral content (BMC) (0.8 ± 0.0158 vs. 0.68 ± 0.0291, p < 0.01). DISCUSSION AND CONCLUSIONS: These findings suggested that FAEE could be used to ameliorate osteoporosis by the MAPK signalling pathway, suggesting that FAEE could be a potential therapeutic candidate for osteoporosis.

A method identifying key optimisation points for aircraft seat comfort.

Seating is the overriding factor influencing aircraft cabin comfort. To efficiently enhance seat comfort, this paper proposes a method to identify key optimisation points for seat comfort. Seat discomfort indicators are recognised based on a comparison of perceived performance with expectation. Confirmatory factor analysis is used to explore the latent variables of discomfort indicators, and a structural model was used to analyse correlations between latent variables. Finally, the most important latent variable influencing seat comfort was clarified. Analysis results of survey data from narrow-body aircraft show that seat discomfort indicators centre on the physical performance of the seat and include four latent variables: support performance, personal space, contact surface features, and safety and stability. Support performance determines body posture while travelling and is the overriding latent variable influencing seat comfort. This research establishes aircraft seat discomfort indicators, latent variables formed through the mutual linkage of discomfort indicators, and the structural relations between latent variables. The results can assist in the formulation of comfort optimisation procedures for aircraft seats. Practitioner summary: A method identifying the key points of aircraft seat comfort optimisation was proposed, which includes three steps: recognising discomfort indicators, exploring the relationship between discomfort indicators, and confirming the most important variable influencing seat comfort. Results provide guidance for aircraft seat optimisation. Abbreviations: SEM: structural equation modelling; EFA: exploratory factor analysis; CFA: confirmatory factor analysis; PA-OV: path analysis with observed variables; CR: construct reliability; AVE: average variance extracted; CMIN: likelihood-ratio chi-square; DF: degrees of freedom; GFI: goodness-of -fit index; AGFI: adjusted goodness-of -fit index; RMSEA: root mean square error of approximation; NNFI: non-normed fit index; RFI: relative fit index; CFI: comparative fit index; CN: critical N.

Hybrid Quantum Device with Nitrogen-Vacancy Centers in Diamond Coupled to Carbon Nanotubes.

We show that nitrogen-vacancy (NV) centers in diamond interfaced with a suspended carbon nanotube carrying a dc current can facilitate a spin-nanomechanical hybrid device. We demonstrate that strong magnetomechanical interactions between a single NV spin and the vibrational mode of the suspended nanotube can be engineered and dynamically tuned by external control over the system parameters. This spin-nanomechanical setup with strong, intrinsic, and tunable magnetomechanical couplings allows for the construction of hybrid quantum devices with NV centers and carbon-based nanostructures, as well as phonon-mediated quantum information processing with spin qubits.

Transcriptional Control: A Directional Sign at the Crossroads of Adult Hepatic Progenitor Cells' Fates.

Hepatic progenitor cells (HPCs) have a bidirectional potential to differentiate into hepatocytes and bile duct epithelial cells and constitute a second barrier to liver regeneration in the adult liver. They are usually located in the Hering duct in the portal vein region where various cells, extracellular matrix, cytokines, and communication signals together constitute the niche of HPCs in homeostasis to maintain cellular plasticity. In various types of liver injury, different cellular signaling streams crosstalk with each other and point to the inducible transcription factor set, including FoxA1/2/3, YB-1, Foxl1, Sox9, HNF4α, HNF1α, and HNF1ß. These transcription factors exert different functions by binding to specific target genes, and their products often interact with each other, with diverse cascades of regulation in different molecular events that are essential for homeostatic regulation, self-renewal, proliferation, and selective differentiation of HPCs. Furthermore, the tumor predisposition of adult HPCs is found to be significantly increased under transcriptional factor dysregulation in transcriptional analysis, and the altered initial commitment of the differentiation pathway of HPCs may be one of the sources of intrahepatic tumors. Related transcription factors such as HNF4α and HNF1 are expected to be future targets for tumor treatment.

Realm of hepatitis E: Challenges and opportunities.

Hepatitis E virus (HEV), responsible for widespread viral hepatitis, infects approximately 2.3 billion individuals globally, with a significant mortality burden in Asia. The virus, primarily transmitted through contaminated water and undercooked meat, is often underdiagnosed, particularly in immunocompromised patients. Current HEV treatments, while effective, are limited by adverse effects, necessitating research into safer alternatives. Moreover, HEV's extrahepatic manifestations, impacting the nervous and renal systems, remain poorly understood. This study underscores the imperative for enhanced HEV research, improved diagnostic methods, and more effective treatments, coupled with increased public health awareness and preventive strategies.

Harvesting Inertial Energy and Powering Wearable Devices: A Review.

Amidst the swift progression of microelectronics and Internet of Things technology, wearable devices are gradually gaining ground in the domains of human health monitoring. Recently, human bioenergy harvesting has emerged as a plausible alternative to batteries. This paper delves into harvesting human inertial energy that stimulates inertial masses through human motion and then transmutes the motion of the inertial masses into electrical energy. The inertial energy harvester is better suited for low-frequency and irregular human motion. This review first identifies the sources of human motion excitation that are compatible with inertial energy harvesters and then provides a summary of the operating principles and the comparisons of the commonly used energy conversion mechanisms, including electromagnetic, piezoelectric, and triboelectric transducers. The review thoroughly summarizes the latest advancements in human inertial energy-harvesting technology that are categorized and grouped based on their excitation sources and mechanical modulation methods. In addition, the review outlines the applications of inertial energy harvesters in powering wearable devices, medical health monitoring, and as mobile power sources. Finally, the challenges faced by inertial energy-harvesting technologies are discussed, and the review provides a perspective on the potential developments in the field.