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Here, we report a differential ring array of piezoelectric micromachined ultrasonic transducers (pMUTs) for ultralong-range detection. Among them, the differential structure is used to improve the sensitivity of the device, and the ring array is used to improve the generated sound intensity. The synergy between the differential structure and the ring array improves the acoustic performance of pMUTs. The piezoelectric material adopts aluminum nitride (AlN) thin film compatible with complementary metal–oxide–semiconductor (CMOS) process. The resonant frequency of the device (80 kHz), the piezoelectric film radius ( $500 \mu \text{m}$ ), and the top electrode ratio were optimized using the finite element method. Compared to pMUTs with central circular electrodes, the differential structure provides two times the low-frequency drive sensitivity and two times the center displacement at the resonant frequency. Seven elements with differential structure were used to form a ring pMUTs array, and the size of the ring pMUTs array was $5\times5$ mm2. Further research shows that the ring pMUTs array can achieve a very large range ( $\ge 0.6$ m) detection, and the range error is less than 2.4 mm. The differential ring pMUTs array provides a valuable reference for obstacle avoidance, flow measurement, liquid-level measurement, and other fields.

Leigh syndrome (LS)/Leigh-like syndrome (LLS) is one of the most common mitochondrial disease subtypes, caused by mutations in either the nuclear or mitochondrial genomes. Here, we identified a novel intronic mutation (c.82-2 A > G) and a novel exonic insertion mutation (c.290dupT) in TMEM126Bfrom a Chinese patient with clinical manifestations of LLS. In silico predictions, minigene splicing assays and patients’ RNA analyses determined that the c.82-2 A > G mutation resulted in complete exon 2 skipping, and the c.290dupT mutation provoked partial and complete exon 3 skipping, leading to translational frameshifts and premature termination. Functional analysis revealed the impaired mitochondrial function in patient-derived lymphocytes due to severe complex I content and assembly defect. Altogether, this is the first report of LLS in a patient carrying mutations in TMEM126B. Our data uncovers the functional effect and the molecular mechanism of the pathogenic variants c.82-2 A > G and c.290dupT, which expands the gene mutation spectrum of LLS and clinical spectrum caused by TMEM126Bmutations, and thus help to clinical diagnosis of TMEM126Bmutation‐related mitochondrial diseases.

As advanced thermal management materials, aerogels have great research value in the fields of engineering insulation, pipeline transportation, and packaging insulation. The composite interaction of the two-phase interface and the construction of a porous structure have an important impact on the thermal properties. Herein, a novel HANRs/SAB composite aerogel was prepared using sodium alginate (SA) with hydroxyapatite nanorods (HANRs), combined with boric acid crosslinking and freeze drying. In the prepared sample, the calcium ions in HANRs and SA formed the first layer of binding force and the chemical crosslinking of sodium alginate with boric acid formed the second layer of strong binding force, which effectively supported the skeleton of the aerogel and enhanced the overall mechanical properties. The modulus and maximum compressive strength of the obtained HANRs/SAB aerogel were 2.39 and 0.75 MPa, respectively, while the bulk density was 0.038–0.068 g·cm–3. Based on the prominent physical structure, the as-prepared HANRs/SAB aerogel exhibited good thermal insulation (∼35.15 mW·m–1·K–1) and outstanding flame retardant performance. Flame-retardant boric acid and high-thermal stability HANRs could effectively prevent heat transfer and organic combustion, thus resulting in an extremely low smoke gas release (11.3 m2m–2). Therefore, the low-cost biopolymer composite aerogel based on a crosslinking strategy has broad application prospects in the field of thermal insulation and flame retardancy.

Cadmium (Cd) is one of the most toxic heavy metal elements to the environment, which seriously threatens the safe production of food crops. In this study, we identified a novel function of the cytomembrane TaSFT2L protein in wheat (Triticum aestivum). Expression of the TaSFT2Lgene in yeast showed no transport activities for Cd, which could explain the role of TaSFT2Lin metal tolerance. It was observed that increased autophagic activity in roots caused by silencing of TaSFT2Lenhanced Cd tolerance. Transgenic wheat revealed that RNA interference (RNAi) lines enhanced the wheat growth concerning the increased shoot or root elongation, dry weight, and chlorophyll accumulation. Furthermore, RNAi lines decreased root-to-grain Cd translocation in wheat by nearly 68% and Cd accumulation in wheat grains by 53%. Meanwhile, the overexpression lines displayed a compromised growth response and increased Cd accumulation in wheat tissues, compared to wild type. These findings show that TaSFT2Lis a key gene involved in regulation of Cd translocation in wheat, and its silencing to form transgenic wheat can inhibit Cd accumulation. This has the ability to alleviate the food chain-associated impact of environmental pollution on human health.

Developing efficient, low-price non-noble metal-based electrocatalysts for overall water splitting in alkaline medium remains a formidable challenge. In our work, Cr-doped CoP/Fe2P (Cr-CoP/Fe2P) flower-like microsphere was synthesized through a simple hydrothermal and phosphating process. The resulting Cr-CoP/Fe2P electrocatalyst shows significantly enhanced oxygen evolution reaction performance (262 mV @ 10 mA cm−2) and has a satisfactory hydrogen evolution reaction performance (114 mV @ 10 mA cm−2), coupled with favorable stability in an alkaline medium. Furthermore, when assembling Cr-CoP/Fe2P into an electrolytic cell, the two-electrode system can provide a current density of 10 mA cm−2at a voltage of 1.61 V. At high current density, the performance of the electrolytic cell composed of Cr-CoP/Fe2P is superior to that of noble metal catalyst electrode pair. Electronic structure analysis and various characterizations confirm that Cr doping and the formation of CoP/Fe2P heterogeneous interfaces redistribute the electron densities of the active sites, enlarge the specific surface area, and enhance the aerophobicity of the catalysts, thereby improving the electrocatalytic property. This work provides a referable method for engineering highly efficient and stable non-noble polymetallic phosphides, which serve as bifunctional electrocatalyst for overall water splitting.

The demand for high quality and effective manufacturing has raised the need for defect identification in friction stir welding. This work aims to identify the tunnel defect inside the welded joint based on the feature of in-situ force signals. First, we measured the traverse force (Fx), lateral force (Fy) and plunge force (Fz) during the welding process and analyzed the variation characteristic of the force signals for the joints with and without tunnel defect. Then, fast Fourier transform was utilized to obtain the frequency components of the force signal for analyzing the cause of the waveform distortion of the welding force, which showed a direct relationship with the occurrence of the tunnel defect in the joint. The combination result of the frequency components indicated that the waveform distortion of Fxand Fyfor the defective joint was mainly influenced by the first harmonic and third harmonic. Thus, a defect detection indicator was proposed by calculating the normalization ratio of the amplitudes of the third harmonic and first harmonic. Tshe best accuracy of the indicator from Fxfor identifying the tunnel defect reached 96.42%. Furthermore, the simulation results of the FSW process provide a physical understanding of material flow and defect formation indicated by the first harmonic and third harmonic of Fx, which helps explain the high accuracy of the proposed indicator from Fxsignal in the detection of tunnel defect.

The novel coronavirus (COVID-19) is spreading globally due to its super contagiousness, and the pandemic caused by it has caused serious damage to the health and social economy of all countries in the world. However, conventional diagnostic methods are not conducive to large-scale screening and early identification of infected persons due to their long detection time. Therefore, there is an urgent need to develop a new COVID-19 test method that can deliver results in real time and on-site. In this work, we develop a fast, ultra-sensitive, and multi-functional plasmonic biosensor based on surface-enhanced infrared absorption for COVID-19 on-site diagnosis. The genetic algorithm intelligent program is utilized to automatically design and quickly optimize the sensing device to enhance the sensing performance. As a result, the quantitative detection of COVID-19 with an ultra-high sensitivity (1.66%/nm), a wide detection range, and a diverse measurement environment (gas/liquid) is achieved. In addition, the unique infrared fingerprint recognition characteristics of the sensor also make it an ideal choice for mutant virus screening. This work can not only provide a powerful diagnostic tool for the ultra-rapid, label-free, and multi-functional detection of COVID-19 but also help gain new insights into the field of label-free and ultrasensitive biosensing.

Exocytosis of a single cell has been extensively researched in recent years due to its close association with numerous diseases. However, current methods only investigate exocytosis at either the single-cell or multiple-cell level, and a method for simultaneously studying exocytosis at both levels has yet to be established. In this study, a combined device incorporating ultramicroelectrode (UME) electrochemistry and surface plasmon resonance (SPR) was developed, enabling the simultaneous monitoring of single-cell and multiple-cell exocytosis. PC12 cells were cultured directly on the SPR sensing Au film, with a carboxylated carbon nanopipette (c-CNP) electrode employed for electrochemical detection in the SPR reaction cell. Upon exocytosis, the released dopamine diffuses onto the inner wall of c-CNP, undergoing an electrochemical reaction to generate a current peak. Concurrently, exocytosis can also induce changes in the refractive index of the Au film surface, leading to the SPR signal. Consequently, the device enables real-time monitoring of exocytosis from both single and multiple cells with a high spatiotemporal resolution. The c-CNP electrode exhibited excellent resistance to protein contamination, high sensitivity for dopamine detection, and the capability to continuously monitor dopamine exocytosis over an extended period. Analysis of both SPR and electrochemical signals revealed a positive correlation between changes in the SPR signal and the frequency of exocytosis. This study introduces a novel method and platform for the simultaneous investigation of single-cell and multiple-cell exocytosis.

Sodium-ion batteries (SIBs) have significant potential for applications in portable electric vehicles and intermittent renewable energy storage due to their relatively low cost. Currently, hard carbon (HC) materials are considered commercially viable anode materials for SIBs due to their advantages, including larger capacity, low cost, low operating voltage, and inimitable microstructure. Among these materials, renewable biomass-derived hard carbon anodes are commonly used in SIBs. However, the reports about biomass hard carbon from basic research to industrial applications are very rare. In this paper, we focus on the research progress of biomass-derived hard carbon materials from the following perspectives: (1) sodium storage mechanisms in hard carbon; (2) optimization strategies for hard carbon materials encompassing design, synthesis, heteroatom doping, material compounding, electrolyte modulation, and presodiation; (3) classification of different biomass-derived hard carbon materials based on precursor source, a comparison of their properties, and a discussion on the effects of different biomass sources on hard carbon material properties; (4) challenges and strategies for practical of biomass-derived hard carbon anode in SIBs; and (5) an overview of the current industrialization of biomass-derived hard carbon anodes. Finally, we present the challenges, strategies, and prospects for the future development of biomass-derived hard carbon materials.

AbstractHDAC6 regulates the expression and activity of various tumor-related proteins, but currently there is no selective inhibitor targeting HDAC6 for clinical application. In order to discover novel HDAC6 inhibitors, virtual screening methods comprised of pharmacophore based virtual screening, molecular docking and molecular dynamics (MD) simulations were employed. 15 molecules were obtained after virtual screening. After in vitro bioassays, two of the hits showed inhibition activity against HDAC6, among which the inhibition activity of G1 to HDAC6 reached 81% at concentration of 20 μM. In addition, the inhibitory activity against HDAC1 and HDAC10 demonstrated that G1 and G10 were highly selective to HDAC6. The analysis of the binding modes of G1 and G10 provides a reference for further development of highly active HDAC6 inhibitors. Communicated by Ramaswamy H. Sarma

Hypomyelinating leukodystrophies (HLDs) are a rare group of disorders characterized by myelin deficit of the brain-based on MRI. Here, we studied 20 patients with unexplained HLD to uncover their genetic etiology through whole-exome sequencing (WES). Trio-based WES was performed for 20 unresolved HLDs families after genetic tests for the PLP1 duplication and a panel of 115 known leukodystrophy-related genes. Variants in both known genes that related to HLDs and promising candidate genes were analyzed. Minigene splicing assay was conducted to confirm the effect of splice region variant. All 20 patients were diagnosed with HLDs clinically based on myelin deficit on MRI and impaired motor ability. Through WES, in 11 of 20 trios, 15 causative variants were detected in seven genes TUBB4A, POLR1C, POLR3A, SOX10, TMEM106B, DEGS1, and TMEM63A. The last three genes have just been discovered. Of 15 variants, six were novel. Using minigene splicing assay, splice variant POLR3Ac.1770 + 5 G > C was proved to disrupt the normal splicing of intron 13 and led to a premature stop codon at position 618 (p.(P591Vfs*28)). Our analysis determined the molecular diagnosis of 11 HLDs patients. It emphasizes the heterogenicity of HLDs, the diagnostic power of trio-based WES for HLDs. Comprehensive analysis including a focus on candidate genes helps to discover novel disease-causing genes, determine the diagnosis for the first time, and improve the yield of WES. Moreover, novel mutations identified in TUBB4A, POLR3A, and POLR1Cexpand the mutation spectrum of these genes.

In this work, a single-layered graphene (SLG)/Au-nanoparticles (NPs)-based Love wave biosensor was prepared for detection of Staphylococcus aureus(S. aureus) gene sequences. The annealing process was proposed to obtain a larger-area interface with ssDNA. The sensitivity was verified by detecting S. aureusgene sequences with a linear detection ranging from 0 to 10 nmol/L, where the limit of detection (LOD) was only 12.4 pg/mL. The stable state of the biosensors based on SLG/Au NPs in the liquid phase could be kept for more than 0.5 h (±0.1°), and the specificity was verified by detecting noncomplementary ssDNA and one- and three-base mismatched ssDNA. The results of our study suggest that a Love wave biosensor based on SLG/Au NPs hold great potential in clinical testing and diagnosis.

Regulating plant density is an important practice to improve winter wheat productivity under limited irrigation in North China Plain. Field experiments were carried out over two seasons (2014–15 and 2015–16) under three plant densities (Dh: 480–570, Dm: 360–390, Dl: 240–270 104plants hm−2) and three irrigation levels (W0: no irrigation; W1: irrigated 80.0 mm only at the jointing stage, which also means limited irrigation; W2: irrigated 60.0 mm each at the jointing and the flowering stages). Results showed that higher numbers of spikes and higher yield were obtained at high density than that at low density under limited irrigation. Under the same irrigation, wheat culms at ripening stage and the proportion of main stem spikes increased with plant density increasing, along with the increasing of transportation amount, transportation rate, and contribution rate of pre-anthesis storage material to grain. But accumulation amount and contribution rate of post-anthesis dry matter, which was influenced by irrigation level, showed a declining trend with increasing plant density under W2 and W1. Therefore, (1) under limited water condition, yield loss could be compensated by increasing contribution rate of pre-anthesis storage material to grain with increasing plant density. (2) Meantime, under the same limited water condition, higher plant densities could promote nitrogen accumulation in grain and plant of wheat, which was significantly correlation to wheat yield. (3) Considering water and nitrogen use efficiency, medium plant density (Dm) is recommended in wet years, high plant density (Dh) may be considered to increase wheat yield in dry years.

Cancer can be considered the result of a series of genetic variations that lead to a normal cell being transformed into a malignant one while avoiding cell death—atypical characteristics of tumor development. Although a large number of genomics and epigenetic alterations have been identified in cells undergoing apoptotic, autophagic or necrotic cell death, the treatment of cancer remains thought-provoking. Pyroptosis is differentiated from other types of programmed cell death and is mainly activated by Caspase-1. To initiate pyroptosis, cells receive specific “death” messages, produce cytokines, swell, burst, and ultimately die. The deficiency of Caspase-1 expression may lead to inflammation-mediated tumor progression. Hence, the molecular mechanisms for the Caspase-1 activation in tumor tissues are yet to be exploited extensively. This review aims to summarise the latest discoveries about pyroptosis and its new exciting role in inducing cancer cell death.

Cobalamin G (cblG) and cobalamin J (cblJ) defects are rare disorders of cbl metabolism caused by MTRand ABCD4mutations, respectively. Patients with atypical biochemical features can be missed by current newborn screening using tandem mass spectrometry (MS/MS), in which total homocysteine (tHCY) in dried blood spots (DBS) is not a primary biomarker. Two Chinese patients suspected of cbl defect but missed by newborn screening were studied. Using comprehensive metabolic analyses including MS/MS assay for tHCY in DBS, slightly low methionine in Patient 1, methymalonic aciduria in Patient 2, and homocysteinemia in both patients were detected, and DBS tHCY of two patients were obviously elevated (59.22 μmol/L, 17.75 μmol/L) compared to 140 healthy controls (2.5th–97.5th percentile, 1.05–8.22 μmol/L). Utilizing whole-exome sequencing, we found two novel MTRvariants c.871C>T (p.Pro291Ser) and c.1771C>T (p.Arg591*) in Patient 1, and a ABCD4homozygous variant c.423C>G (p.Asn141Lys) in Patient 2. Our study identified the first cblG patient and cblJ patient in mainland China, and highlighted comprehensive metabolic analyses and genetic tests in patients suspected of cbl defects. It also indicated that supplementary MS/MS assay for tHCY in DBS may be practical for early diagnosis of homocysteinemia, without repeated blood sampling.

Following publication of the original article, the authors noticed some errors in Figs. 1–3. The correct figures can be found in the correction.

Following publication of the original article, the authors noticed some errors in Figs. 1–3. The correct figures can be found in the correction.

Friction stir additive manufacturing (FSAM) was performed successfully using 2 mm thick sheets of 2195-T8 aluminum-lithium alloy. The influence of the tool pin shape and process parameters on the interfacial bonding features among the additive manufactured layers was discussed, and the effects of interfacial defects on the performances of the additive build were analyzed based on microstructures, hardness profiles, and mechanical property evaluations. It is shown that the shape of the tool pin is one of the key factors in influencing the bonding interface between two manufactured layers. The cylindrical pin and the conical pin with three flats are not suitable for the FSAM process since very poor material mixing features are produced along the bonding interface. Although the material mixing degree of bonding interface is obviously improved at the advancing side (AS) interface of the nugget zone (NZ) by using the convex featured pin or the pin with three concave arc grooves, the material mixing degree at the retreating side (RS) interface of the NZ is always insufficient. Meanwhile, the weak-bonding defects along the bonding interfaces could be formed, which are originated from the hooking defects on the RS. The weak-bonding defects are related to the oxides and impurities existing at the original bonding interfaces as well as the insufficient stirring action of the tool pin. The back and forth double passes welding is one of the effective methods to improve the material mixing in the whole NZ and eliminate the hooking defects extending into the NZ. The welding rotation speeds of 800, 900 and 1000 rpm for giving welding speed of 100 mm/min were used in the additive manufacturing processes of 2195-T8 aluminum-lithium alloy, in which the optimum microstructure is obtained with the rotation speed of 800 rpm. The soften degree for the multilayered build is obvious, and the hardness profiles across the different bonding interfaces are always uneven. Meanwhile, compared with the AS interface, the fluctuation of the hardness value at the RS interface is greater. The mechanical properties of the multilayered build are inhomogeneous, and the maximum tensile strength of the multilayered build is only reached the 56.6% of the base metal. The mechanical properties are closely associated with the soften tendency of the material and the degree of the amelioration of weak-bonding defect along the bonding interface.

Liver fibrosis is a worldwide clinical issue. The activation of hepatic stellate cells (HSCs) is the central event during the hepatic fibrotic response. However, the exact mechanisms related to HSC activation and the connection between hepatocytes and HSCs remain unclear. We elucidated the mechanism by which the nuclear-damage-associated molecular pattern molecule, high-mobility group box 1 (HMGB1) was released from the impaired hepatocytes and induced endoplasmic reticulum stress to activate HSCs. In this work, we demonstrated that HMGB1 can be released from hepatocytes and the released HMGB1 activates the HSCs via ER stress at the transcriptional level which was dependent on the activation of both the TLR4 and RAGE signaling pathways rather than the TLR2 signaling pathway. HMGB1 induction of proinflammatory cytokines interleukin (IL)-1β and IL-18 release was dependent on ER stress. In vivo, stable inhibition of HMGB1 suppressed liver fibrosis. These results suggest that under damage condition, HMGB1 can be secreted from injured hepatocytes and activates TLR4- and RAGE signaling pathways to induce ER stress which activates HSCs. Moreover, HMGB1 can produce multiple inflammatory mediators through ER stress, which, in turn, promote liver fibrosis.

Liver fibrosis is a worldwide clinical issue. The activation of hepatic stellate cells (HSCs) is the central event during the hepatic fibrotic response. However, the exact mechanisms related to HSC activation and the connection between hepatocytes and HSCs remain unclear. We elucidated the mechanism by which the nuclear-damage-associated molecular pattern molecule, high-mobility group box 1 (HMGB1) was released from the impaired hepatocytes and induced endoplasmic reticulum stress to activate HSCs. In this work, we demonstrated that HMGB1 can be released from hepatocytes and the released HMGB1 activates the HSCs via ER stress at the transcriptional level which was dependent on the activation of both the TLR4 and RAGE signaling pathways rather than the TLR2 signaling pathway. HMGB1 induction of proinflammatory cytokines interleukin (IL)-1β and IL-18 release was dependent on ER stress. In vivo, stable inhibition of HMGB1 suppressed liver fibrosis. These results suggest that under damage condition, HMGB1 can be secreted from injured hepatocytes and activates TLR4- and RAGE signaling pathways to induce ER stress which activates HSCs. Moreover, HMGB1 can produce multiple inflammatory mediators through ER stress, which, in turn, promote liver fibrosis.

SLC26A3encodes a Cl−/HCO3−ion transporter that is also known as downregulated in adenoma (DRA) and is involved in HCO3−/mucus formation. The role of DRA in the epithelial barrier has not been previously established. In this study, we investigated the in vivo and in vitro mechanisms of DRA in the colon epithelial barrier. Immunofluorescence (IF) and co-immunoprecipitation (co-IP) studies reveal that DRA binds directly to tight junction (TJ) proteins and affects the expression of TJ proteins in polarized Caco-2BBe cells. Similarly, DRA colocalizes with ZO-1 in the intestinal epithelium. Knockdown or overexpression of DRA leads to alterations in TJ proteins and epithelial permeability. In addition, TNF-α treatment downregulates DRA by activating NF-кB and subsequently affecting intestinal epithelial barrier integrity. Furthermore, overexpression of DRA partly reverses the TNF-α-induced damage by stabilizing TJ proteins. Neutralization of TNF-α in dextran sulfate sodium (DSS)-induced colitis mice demonstrates improved the outcomes, and the therapeutic effect of the TNF-α neutralizing mAb is mediated in part by the preservation of DRA expression. These data suggest that DRA may be one of the therapeutic targets of TNF-α. Moreover, DRA delivered by adenovirus vector significantly prevents the exacerbation of colitis and improves epithelial barrier function by promoting the recovery of TJ proteins in DSS-treated mice. In conclusion, DRA plays a role in protecting the epithelial barrier and may be a therapeutic target in gut homeostasis.

SLC26A3encodes a Cl−/HCO3−ion transporter that is also known as downregulated in adenoma (DRA) and is involved in HCO3−/mucus formation. The role of DRA in the epithelial barrier has not been previously established. In this study, we investigated the in vivo and in vitro mechanisms of DRA in the colon epithelial barrier. Immunofluorescence (IF) and co-immunoprecipitation (co-IP) studies reveal that DRA binds directly to tight junction (TJ) proteins and affects the expression of TJ proteins in polarized Caco-2BBe cells. Similarly, DRA colocalizes with ZO-1 in the intestinal epithelium. Knockdown or overexpression of DRA leads to alterations in TJ proteins and epithelial permeability. In addition, TNF-α treatment downregulates DRA by activating NF-кB and subsequently affecting intestinal epithelial barrier integrity. Furthermore, overexpression of DRA partly reverses the TNF-α-induced damage by stabilizing TJ proteins. Neutralization of TNF-α in dextran sulfate sodium (DSS)-induced colitis mice demonstrates improved the outcomes, and the therapeutic effect of the TNF-α neutralizing mAb is mediated in part by the preservation of DRA expression. These data suggest that DRA may be one of the therapeutic targets of TNF-α. Moreover, DRA delivered by adenovirus vector significantly prevents the exacerbation of colitis and improves epithelial barrier function by promoting the recovery of TJ proteins in DSS-treated mice. In conclusion, DRA plays a role in protecting the epithelial barrier and may be a therapeutic target in gut homeostasis.

Activation of the platelet-derived growth factor (PDGF)/PDGF beta receptor (PDGFβR) axis has a critical role in liver fibrosis. However, the mechanisms that regulate the PDGF signaling are yet to be elucidated. The present study demonstrates that paired related homeobox protein 1 (Prrx1) is involved in PDGF-dependent hepatic stellate cell (HSCs) migration via modulation of the expression of metalloproteinases MMP2 and MMP9. PDGF elevated the level of Prrx1 through the activation of ERK/Sp1 and PI3K/Akt/Ets1 pathways. In vivo, an adenoviral-mediated Prrx1 shRNA administration attenuated liver fibrosis in thioacetamide-induced fibrotic models. These studies reveal a role of Prrx1 as a modulator of PDGF-dependent signaling in HSCs, and inhibiting its expression may offer a therapeutic approach for hepatic fibrosis.

Activation of the platelet-derived growth factor (PDGF)/PDGF beta receptor (PDGFβR) axis has a critical role in liver fibrosis. However, the mechanisms that regulate the PDGF signaling are yet to be elucidated. The present study demonstrates that paired related homeobox protein 1 (Prrx1) is involved in PDGF-dependent hepatic stellate cell (HSCs) migration via modulation of the expression of metalloproteinases MMP2 and MMP9. PDGF elevated the level of Prrx1 through the activation of ERK/Sp1 and PI3K/Akt/Ets1 pathways. In vivo, an adenoviral-mediated Prrx1 shRNA administration attenuated liver fibrosis in thioacetamide-induced fibrotic models. These studies reveal a role of Prrx1 as a modulator of PDGF-dependent signaling in HSCs, and inhibiting its expression may offer a therapeutic approach for hepatic fibrosis.

Mutiview plus associated depth information form a typical 3D video representation. Depth map of each frame in a video sequence is usually estimated by stereo matching approaches separately. As a result it has weak temporal consistency. In this paper, we propose a novel framework based on spatio-temporal Markov Random Fields. It enforces temporal correlation by employing additional state in the graphical model. Improved belief propagation-sequential algorithm is exploited as an efficient optimization scheme to minimize the energy function. The experimental results demonstrate that the proposed method produces dependable depth maps in both spatial and temporal domain.

Abstract??An investigation was made to study the processes of fed-batch cultures of a hybridoma cell line in chemically defined protein-free media. First of all, a strong growth-associated pattern was correlated between the production of MAb and growth of cells through the kinetic studies of batch cultures, suggesting the potential effectiveness of extending the duration of exponential growth in the improvement of MAb titers. Second, compositions of amino acids in the feeding solution were balanced stepwisely according to their stoichiometrical correlations with glucose uptake in batch and fed-batch cultures. Moreover, a limiting factor screening revealed the constitutive nature of Ca2+and Mg2+for cell growth, and the importance of their feeding in fed-batch cultures. Finally, a fed-batch process was executed with a glucose uptake coupled feeding of balanced amino acids together with groups of nutrients and a feeding of CaCl2and MgCl2concentrate. The duration of exponential cell growth was extended from 70?h in batch culture and 98?h in fed-batch culture without Ca2+/Mg2+feeding to 117?h with Ca2+/Mg2+feeding. As a result of the prolonged exponential cell growth, the viable and total cell densities reached 7.04???106and 9.12???106cells ml?1, respectively. The maximal MAb concentration achieved was increased to approximately eight times of that in serum supplemented batch culture.

We propose a new mechanism, parallel quantum Zeno dynamics, to dissipatively prepare all Bell entangled states of the two-qubit system in the context of cavity quantum electrodynamics. This mechanism can provide two transition channels between ground states and two different dark states simultaneously, which efficiently speeds up the stabilization of the entanglement and suppresses the adverse influence of surrounding environments. In addition, there is no need for the initialization of quantum states and the Clauser-Horne-Shimony-Holt inequality can be violated in a finite temperature bath. The experimental feasibility is also studied by the state-of-the-art technique and a high fidelity about 99% can be achieved.