Biology of Hippo signaling pathway:Skeletal muscle development and beyond

Global demand for farm animals and their meat products i.e.,pork,chicken and other livestock meat,is steadily incresing.With the ongoing life science research and the rapid development of biotechnology,it is a great opportunity to develop advanced molecular breeding markers to efficiently improve animal meat production traits.Hippo is an important study subject because of its crucial role in the regulation of organ size.In recent years,with the increase of research on Hippo signaling pathway,the integrative application of multi-omics technologies such as genomics,transcriptomics,proteomics,and metabolomics can help promote the in-depth involvement of Hippo signaling pathway in skeletal muscle development research.The Hippo signaling pathway plays a key role in many biological events,including cell division,cell migration,cell proliferation,cell differentiation,cell apoptosis,as well as cell adhesion,cell polarity,homeostasis,maintenance of the face of mechanical overload,etc.Its influence on the development of skeletal muscle has important research value for enhancing the efficiency of animal husbandry production.In this study,we traced the origin of the Hippo pathway,comprehensively sorted out all the functional factors found in the pathway,deeply analyzed the molecular mechanism of its function,and classified it from a novel perspective based on its main functional domain and mode of action.Our aim is to systematically explore its regulatory role throughout skeletal muscle development.We specifically focus on the Hippo signaling pathway in embryonic stem cell development,muscle satellite cell fate determination,myogenesis,skeletal muscle meat production and organ size regulation,muscle hypertrophy and atrophy,muscle fiber formation and its transformation between different types,and cardiomyocytes.The roles in proliferation and regeneration are methodically summarized and analyzed comprehensively.The summary and prospect of the Hippo signaling pathway within this article will provide ideas for further improving meat production and muscle deposition and developing new molecular breeding technologies for livestock and poultry,which will be helpful for the development of animal molecular breeding.

Electrochemical synthesis of trimetallic nickel-iron-copper nanoparticles via potential-cycling for high current density anion exchange membrane water-splitting applications

Hydrogen is known for its elevated energy density and environmental compatibility and is a promising alternative to fossil fuels.Alkaline water electrolysis utilizing renewable energy sources has emerged as a means to obtain high-purity hydrogen.Nevertheless,electrocatalysts used in the process are fabricated using conventional wet chemical synthesis methods,such as sol-gel,hydrothermal,or surfactantassisted approaches,which often necessitate intricate pretreatment procedures and are vulnerable to post-treatment contamination.Therefore,this study introduces a streamlined and environmentally conscious one-step potential-cycling approach to generate a highly efficient trimetallic nickel-iron-copper electrocatalyst in situ on nickel foam.The synthesized material exhibited remarkable performance,requiring a mere 476 mV to drive electrochemical water splitting at 100 mA cm^(-2)current density in alkaline solution.Furthermore,this material was integrated into an anion exchange membrane watersplitting device and achieved an exceptionally high current density of 1 A cm^(-2)at a low cell voltage of2.13 V,outperforming the noble-metal benchmark(2.51 V).Additionally,ex situ characterizations were employed to detect transformations in the active sites during the catalytic process,revealing the structural transformations and providing inspiration for further design of electrocatalysts.

Metabolite acetyl-L-carnitine participates in Bifidobacterium animalis F1-7 to ameliorate atherosclerotic inflammation by downregulating theTLR4/NF-κB pathway

This study aimed to explore the effect of Bifidobacterium animalis F1-7 on the improvement of atherosclerotic inflammation.Arteriosclerosis model ApoE^(-/-)mice were orally administered with B.animalis F1-7 for 12 weeks.The probiotic intervention reduced the plaque areas in aorta and the accumulation of macrophages,and downregulated the expression of toll-like receptor 4(TLR4)/nuclear factorκB(NF-κB)pathway to reduce the levels of inflammatory factors.The widely-targeted metabolomics analysis showed that acetyl-L-carnitine(ALC)in the intestine of atherosclerotic mice was significantly increased after B.animalis F1-7 intervention.Correlation analysis proved that ALC was associated with atherosclerotic inflammatory response.By using oxidized low density lipoprotein induced macrophage foam cells,we further verified that ALC could reduce lipid accumulation and inflammatory response in foam cells by downregulating the TLR4/NF-κB pathway.Finally,our results revealed that B.animalis F1-7 upregulated the metabolite ALC to downregulate the inflammatory responses,leading to the reduction of plaque accumulation of atherosclerosis.

Genomic alterations in oral multiple primary cancers

Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n=202) and oral MPCs (n=34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in MPCs.Moreover, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8, TP53 and MUC16, in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A. Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.

Numerical Investigation of an Idealized Total Cavopulmonary Connection Physiology Assisted by the Axial Blood Pump With and Without Diffuser

In order to improve the surgical treatment of the congenital heart disease patient with single ventricle defect,two axial flow blood pumps,one with diffuser and the other without diffuser,were designed and virtually implanted into an idealized total cavopulmonary connection(TCPC)model to form two types of Pump-TCPC physiological structure.Computational fluid dynamics(CFD)simulationswere performed to analyze the variations of the hemodynamic characteristics,such as flow field,wall shear stress(WSS),oscillatory shear index(OSI),relative residence time(RRT),between the two Pump-TCPC models.Numerical results indicate that the Pump-TCPC with diffuser has better flow field stability,less damage on endothelial cell of vessel wall,and lower risk of vascular injury and thrombosis formation than that without diffuser.

Effect of the Wall Thickness of the Vessel on FFRCT of Carotid Artery Stenosis

Fractional flow reserve(FFR)computed from computed tomography angiography(CTA),i.e.,FFRCT has been used in the clinic as a noninvasive parameter for functional assessment of coronary artery stenosis.It has also been suggested to be used in the assessment of carotid artery stenosis.The wall thickness of the vessel is an important parameter when establishing a fluid-structure coupling model of carotid stenosis.This work studies the effect of the vessel wall thickness on hemodynamic parameters such as FFRCT in carotid stenosis.Models of carotid stenosis are established based on CTA image data using computer-aided design software.It is assumed that the vessel wall is a linear elastic and isotropic material,and the blood an incompressible Newtonian fluid.Under the pulsating flow condition,ANSYS Transient Structural and CFX are used to simulate the blood flow of fluid-structure coupling in the carotid stenosis model in order to obtain hemodynamic parameters and the corresponding FFRCT.The results show that when the elastic modulus of the vessel wall is fixed,FFRCT will decrease with the increase of the wall thickness.Similarly,FFRCT will decrease with the increase of the elastic modulus when the wall thickness is fixed.The difference in hemodynamic parameters such as FFRCT,however,is relatively small if the stiffness of the two models are close.The results demonstrate that the effect of the vessel wall thickness,especially for a model with small elastic modulus,should be taken into account in using FFRCT for functional assessment of carotid stenosis.Moreover,under the linear elasticity and isotropic material assumptions,the stiffness coefficient may replace the elastic modulus and wall thickness as a parameter reflecting material property of the vessel wall in the carotid stenosis model.

Analysis of the Errors in the Chinese Students’Composition

Writing is a complicated process and being able to write well is usually considered to be the last skill in language learning.Teachers firstly need to find out the errors the Chinese students made in their English writing process in order to improve students’writing ability.Errors are common characteristic of language acquisition and learning.Via studying the types of errors on the basis of error analysis theory,the author hopes to seek an effective approach to the teaching of English writing.

A New Thioimide-Based Fluorescent ＇Turn-On＇ and Chromogenic Chemodosimeter in Acetonitrile and Its Nanoparticles in Water for Highly Selective and Sensitive Detection of Hg^2＋

A new thioimide-based fluorescent ‘turn-on’ and chromogenic chemodosimeter for highly selective and sensitive detection of Hg^2＋ has been developed. The dual response of Hg^2＋ was not only in the marked color change of the solution from dark green to colorless, but also in the significant enhancement of the fluorescent intensity of the chemodosimeter in aqueous acetonitrile. Moreover, when the chemodosimeter was assembled into nanoparticles, it could also exhibit remarkably dual response of color change and fluorescence enhancement for detection of Hg^2＋.

Overexpression of netrin-1 improves neurological outcomes in mice following transient middle cerebral artery occlusion

Netrin-1(NT-1)is one of the axon-guiding molecules that are critical for neuronal development.Because of its structural homology to the endothelial mitogens,NT-1 may have similar effects on vascular network formation.NT-1 was shown to be able to stimulate the proliferation and migration of human cerebral endothelial cells in vitro and also promote focal neovascularization in adult brain in vivo.In the present study,we reported the delivery of NT-1 using an adeno-associated virus(AAV)vector(AAV-NT-1)into mouse brain followed by transient middle cerebral artery occlusion(tMCAO).We found that AAV vectors did not elicit a detectable inflammatory response,cell loss or neuronal damage after brain transduction.The level of NT-1 was increased in the AAV-NT-1-transduced tMCAO mice compared with the control mice.Furthermore,the neurobehavioral outcomes were significantly improved in AAV-NT-1-transduced mice compared with the control animals(P<0.05)7 days after tMCAO.Our data suggests that NT-1 plays a neuronal function recovery role in ischemic brain and that NT-1 gene transfer might present a valuable approach to treat brain ischemic disorders.

A Neural Circuit Mechanism Controlling Breathing by Leptin in the Nucleus Tractus Solitarii

Leptin,an adipocyte-derived peptide hormone,has been shown to facilitate breathing.However,the central sites and circuit mechanisms underlying the respiratory effects of leptin remain incompletely understood.The present study aimed to address whether neurons expressing leptin receptor b(LepRb)in the nucleus tractus solitarii(NTS)contribute to respiratory control.Both chemogenetic and optogenetic stimulation of LepRb-ex-pressing NTS(NTS^(LepRb))neurons notably activated breathing.Moreover,stimulation of NTS^(LepRb) neurons projecting to the lateral parabrachial nucleus(LPBN)not only remarkably increased basal ventilation to a level similar to that of the stimulation of all NTS^(LepRb) neurons,but also activated LPBN neurons projecting to the preBotzinger complex(preBotC).By contrast,ablation of NTS^pRb neurons projecting to the LPBN notably eliminated the enhanced respiratory effect induced by NTSLepRb neuron stimulation.In brainstem slices,bath application of leptin rapidly depolarized the membrane potential,increased the spontaneous firing rate,and accelerated the Ca2+transients in most NTSLepRb neurons.Therefore,leptin potentiates breathing in the NTS most likely via an NTS-LPBN-preBdtC circuit.

A 220 GHz dynamic frequency divider in 0.5μm InP DHBT technology

A high performance 3 inch 0.5 μm InP DHBT technology with three interconnecting layers has been developed.The epitaxial layer structure and geometry parameters of the device were carefully studied to get the required performances.The 0.5 × 5 μm^2 InP DHBTs demonstrated ft = 350 GHz,f（max） = 532 GHz and BV（CEO） = 4.8 V,which were modeled using Agilent-IIBT large signal model.As a benchmark circuit,a dynamic frequency divider operating from 110 to 220 GHz has been designed,fabricated and measured with this technology.The ultra-high-speed 0.5 μm InP DHBT technology offers a combination of ultra-high-speed and high breakdown voltage,which makes it an ideal candidate for next generation 100 GHz＋ mixed signal integrated circuits.

Palladium-catalyzed cascade synthesis of spirocyclic oxindoles via regioselective C2-H arylation and C8-H alkylation of naphthalene ring

A simultaneous C2-H arylation and C8-H alkylation of naphthalene ring has been achieved by palladiumcatalyzed cascade reaction of N-(2-halophenyl)-2-(naphthalen-1-yl)acrylamides with aryl iodides,which provides an efficient method for synthesizing various aryl-substituted spirocyclic oxindoles.The protocol enables three C-C bonds formation via an intramolecular Heck reaction and sequentially regioselective C-H bond activation.

An investigation of the DC and RF performance of InP DHBTs transferred to RF CMOS wafer substrate

This paper investigated the DC and RF performance of the In P double heterojunction bipolar transistors（DHBTs）transferred to RF CMOS wafer substrate.The measurement results show that the maximum values of the DC current gain of a substrate transferred device had one emitter finger,of 0.8μm in width and 5μm in length,are changed unobviously,while the cut-off frequency and the maximum oscillation frequency are decreased from 220to 171 GHz and from 204 to 154 GHz,respectively.In order to have a detailed insight on the degradation of the RF performance,small-signal models for the In P DHBT before and after substrate transferred are presented and comparably extracted.The extracted results show that the degradation of the RF performance of the device transferred to RF CMOS wafer substrate are mainly caused by the additional introduced substrate parasitics and the increase of the capacitive parasitics induced by the substrate transfer process itself.