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The performance of organic‐inorganic hybrid solar cells (HSCs) can be improved by modifying the hole transport layer (HTL). Poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) is the most active HTL material in organic‐inorganic HSCs and has been widely studied. Nevertheless, charge transfer in PEDOT:PSS is limited and inefficient due to the presence of the weak ionic conductor PSS. Moreover, the working function of the PEDOT:PSS film and the passivation of the PSS at the Si/PEDOT:PSS interface play a crucial role in carrier separation. The focus of this work is to explore a universal modification method to simultaneously achieve improved charge transport and interfacial passivation capability when using PEDOT:PSS as HTL. By combining bilayer design and simple solution posttreatment, the direct current conductivity (σdc) and work function of the HTL based on PEDOT:PSS are increased to 765 S cm−1 and 5.00 eV, respectively. The organic‐inorganic HSCs prepared using this approach achieve a photovoltaic conversion efficiency (PCE) of 12.33%, achieving a 16.54% improvement over untreated devices. [ABSTRACT FROM AUTHOR]

With the introduction of the concept of dopant‐free carrier‐selective contact for c‐Si photovoltaics, Si‐based heterojunction solar cells can greatly reduce production costs by optimizing the manufacturing process while maintaining high power conversion efficiency. Compared with processes that rely on complex vacuum equipment, low‐temperature solution processing has many advantages over conventional silicon solar cells. However, research on low‐cost and high‐efficiency solar cells based on p‐type crystalline silicon is relatively rare. From the point of view regards energy band matching, the inorganic metal oxide semiconductor material ZnO is well suited for low‐cost solution method studies due to its easy preparation, very high transmittance in the visible spectrum, low cost, and suitable energy levels matching p‐Si. Herein, ZnO is spin coated on the back of p‐Si to form a heterojunction, together with spin coating of PEDOT:PSS on the front side as the hole transport layer and passivation layer, a PEDOT:PSS/p‐Si/ZnO‐structured p‐Si‐based backcontact hybrid solar cell is successfully fabricated at low temperature (≤135 °C) via solution process with a PCE of 9.77% (Voc = 0.56 V, Jsc = 25.99 mA cm−2, fill factor = 67.10%). This work provides a promising approach for fabricating high‐performance and low‐cost silicon‐based heterojunction solar cells. [ABSTRACT FROM AUTHOR]

Aluminum scandium nitride (Al1−xScxN) film has drawn considerable attention owing to its enhanced piezoelectric response for micro-electromechanical system (MEMS) applications. Understanding the fundamentals of piezoelectricity would require a precise characterization of the piezoelectric coefficient, which is also crucial for MEMS device design. In this study, we proposed an in situ method based on a synchrotron X-ray diffraction (XRD) system to characterize the longitudinal piezoelectric constant d33 of Al1−xScxN film. The measurement results quantitatively demonstrated the piezoelectric effect of Al1−xScxN films by lattice spacing variation upon applied external voltage. The as-extracted d33 had a reasonable accuracy compared with the conventional high over-tone bulk acoustic resonators (HBAR) devices and Berlincourt methods. It was also found that the substrate clamping effect, leading to underestimation of d33 from in situ synchrotron XRD measurement while overestimation using Berlincourt method, should be thoroughly corrected in the data extraction process. The d33 of AlN and Al0.9Sc0.1N obtained by synchronous XRD method were 4.76 pC/N and 7.79 pC/N, respectively, matching well with traditional HBAR and Berlincourt methods. Our findings prove the in situ synchrotron XRD measurement as an effective method for precise piezoelectric coefficient d33 characterization. [ABSTRACT FROM AUTHOR]

Sandwich structures with optimized foam core have received considerable attention. The objective of this study is to investigate the indentation of sandwich beams with a two-layer core gradation. An analytical model is developed to predict the large indentation deflections of sandwich beams with two-layer metal foam cores subjected to the concentrated loading. Analytical predictions are compared with finite element simulations and good agreement is obtained. The effects of face sheet strength, core strength, and thickness ratio on the initial failure load of sandwich beams with core gradation are discussed in detail. The results show that through variation of the core thickness ratio and core strength ratio, the failure mode of sandwich beams could be controlled. Meanwhile, the load-carrying and energy absorption capacity of the sandwich beams can also be improved. This work is useful in the core design of the sandwich structures. [ABSTRACT FROM AUTHOR]

Abstract: Dendritic cells (DCs) have been identified as the most effective antigen-presenting cell (APC), much attention has been directed toward the use of DCs in vaccine strategies for the treatment of cancer or chronic virus infection. B7-H1 (PD-L1) is a ligand for programmed cell death-1 (PD-1) and does not bind to other CD28 family members, it is expressed on resting and upregulated on activated B, T, myeloid, and dendritic cells (DCs). The overwhelming number of studies supports the role of B7-H1 as a negative regulator of T cell responses. RNA interference (RNAi) is a mechanism for sequence-specific posttranscriptional inhibition of gene expression via double stranded RNA molecules and it has recently been applied to mammalian cells with the use of small interfering RNAs (siRNAs). In the study, transfection of DCs with siRNA specific for B7-H1 gene resulted in the blockade of the expression of B7-H1 on DCs. The allostimulatory activity of DCs could be enhanced by silencing of B7-H1 on DCs. Blockade of B7-H1 on DCs inhibited the production of IFN-γ and IL-10 but not IL-2 and IL-4 in mixed lymphocyte reaction (MLR). HBV specific peptide-pulsed DCs could break tolerance and trigger specific CTL responses, the level of HBsAg and HBV DNA in sera of HBV transgenic mice decreased, whereas blockade of B7-H1 on DCs augmented the effects. These data strongly support the concept that blockade of B7-H1 can enhance DC-mediated antiviral immune responses. [Copyright &y& Elsevier]

Abstract: DNA vaccines could induce protective immune responses in several animal models. Many strategies have been employed to improve the effect of nucleic acid vaccines. LIGHT is a member of the TNF superfamily and functions as a co-stimulatory molecule for T cell proliferation. In the study, the immunogenicity in the induction of humoral and cellular immune responses by HBV DNA vaccine and the adjuvant effect of LIGHT were studied in a murine model. The eukaryotic expression plasmid pcDNA-L was constructed by inserting mouse LIGHT gene into the vector pcDNA3.1(+). In vitro expression of LIGHT was detected by RT-PCR and indirect immunofluorescence assay in transfected HeLa cells. MLR assay showed that LIGHT-transfected DCs induced markedly higher allogeneic lymphocyte proliferation than pcDNA-transfected DCs and untreated DCs at all dilutions. After BALB/c mice were immunized by three intramuscular injections of the HBV DNA vaccine plasmids alone or in combination with LIGHT expression plasmids, the different levels of anti-HBV immune responses were measured comparable to the control groups immunized with parent plasmid pcDNA or PBS. The HBsAg-specific splenocytes proliferation and specific cytotoxic activities of splenic CTLs in the coinoculation group were both significantly higher than those in the HBV DNA single inoculation group, and an enhancement of antibody response was also observed in the coinoculation group compared with the single inoculation group. Taken together, coimmunization of HBV DNA vaccine plasmids and LIGHT expression plasmids can elicit stronger humoral and cellular immune responses in mice than HBV DNA vaccine plasmids alone, and LIGHT may be an effective immunological adjuvant in HBV DNA vaccination. [Copyright &y& Elsevier]

Abstract: Numerous strategies have been employed in an attempt to improve the immunogenicity and efficacy of nucleic acid vaccines. In the present study, the immunogenicity in the induction of humoral and cellular immune responses to HIV-1 DNA vaccine expressing a chimeric gene of gag and gp120 and the adjuvant effect of IFN-α on HIV-1 DNA vaccine were studied in a murine model. The DNA vaccine plasmid pVAX1-gag-gp120 and eukaryotic expression plasmid pVAX1-IFN were constructed by inserting the chimeric gene of gag and gp120 of HIV-1 and IFN-α into the downstream of CMV promoter of eukaryotic expression vector pVAX1, respectively. In vitro expression detected by RT-PCR and Western blotting showed that the genes of interest could be expressed in transfected HeLa cells. After BALB/c mice were immunized by three intramuscular inoculations of the HIV-1 DNA vaccine plasmids alone or in combination with IFN-α expression plasmids, the different levels of anti-HIV-1 humoral and cellular responses were measured comparable to the control groups immunized with pVAX1-IFN, parent plasmid pVAX1 or PBS. The percentage of CD3+CD4+ and CD3+CD8+ subgroups of spleen T lymphocytes and the specific cytotoxicity activities of splenic CTLs in the coinoculation group were significantly higher than those in the separate inoculation group, and an enhancement of antibody response was also observed in the coinoculation group compared with the separate inoculation group. Take together, coadministration of HIV-1 DNA vaccine plasmids and IFN-α expression plasmids can elicit stronger humoral and cellular immune responses in mice than HIV-1 DNA vaccine plasmids alone, and IFN-α can be an effective immunological adjuvant in DNA vaccination against HIV-1. [Copyright &y& Elsevier]

Abstract: DNA vaccines have a demonstrated ability to induce humoral and cellular immune responses in animal models and humans. To analyze the immunogenicity of HIV-1 DNA vaccine which expressing the chimeric gene gag-gp120 of Chinese prevalent HIV-1 strain and the immunoregulatory activity of IL-6, DNA vaccine plasmid pVAX1-gag-gp120 and eukaryotic expression plasmid pVAX1-IL6 were constructed and the expression in vitro was detected by RT-PCR and Western blotting, the results showed that the gene of interest expressed in the transfected HeLa cells. To explore the immune response in mice coinoculated with HIV-1 DNA vaccine and IL-6 expression plasmid, BALB/c mice were injected i.m. with eukaryotic expression plasmid pVAX1-IL6 and DNA vaccine plasmid pVAX1-gag-gp120. The specific humoral and cellular immunity in mice could be induced by inoculating separately HIV-1 DNA vaccine plasmid or coinoculating with IL-6 expression plasmid, and the specific killing activities of spleen CTL and the level of serum antibodies in the coinoculation group were significantly higher than those in the separate inoculation group. These results strongly support the use of IL-6 as a cytokine adjuvant in DNA vaccination. [Copyright &y& Elsevier]

Abstract: The acquired immunodeficiency syndrome (AIDS) has now become one of the most serious infectious disease in the world, the safe and effective AIDS vaccines would be the best tools to control the disease. Fowlpox virus has been studied recently as a potential vector for the delivery of heterologous vaccine antigen. In this study, a recombinant fowlpox virus coexpressing gp120 of Chinese prevalent HIV-1 strain and IL-2 was constructed and the cellular immune responses against HIV-1 gp120 in BALB/c mice were evaluated. Chinese vaccine strain 282E4 of fowlpox virus was used as the vector to construct the recombinant fowlpox virus (rFPV) coexpressing HIV-1 gp120 and IL-2 via homologous recombination, and the recombinant virus was identified by PCR and Western blotting. The specific DNA fragment was amplified by PCR from the genomes of rFPV. Western blotting analysis showed that HIV-1 gp120 and IL-2 was expressed not only in chicken embryo fibroblast (CEF) cells infected by rFPV, but also in mammalian cells infected by rFPV. After the recombinant fowlpox virus was inoculated into BALB/c mice, specific CTL activities in the immunized mice were detected in the spleen. The results demonstrated that rFPV had good immunogenicity and could induce BALB/c mice to produce specific cellular immunity. IL-2 played a role of immunoadjuvant and enhanced the cellular immune response. The study provides the basis for the preparation of a Chinese vaccine candidate against HIV-1. [Copyright &y& Elsevier]

CD19-specific CAR-T immunotherapy has been extensively studied for the treatment of B-cell lymphoma. Recently, cholesterol metabolism has emerged as a modulator of T lymphocyte function and can be exploited in immunotherapy to increase the efficacy of CAR-based systems. Acetyl-CoA acetyltransferase 1 (ACAT1) is the major cholesterol esterification enzyme. ACAT1 inhibitors previously shown to modulate cardiovascular diseases are now being implicated in immunotherapy. In the present study, we achieved knockdown of ACAT1 in T cells via RNA interference technology by inserting ACAT1-shRNA into anti-CD19-CAR-T cells. Knockdown of ACAT1 led to an increased cytotoxic capacity of the anti-CD19-CAR-T cells. In addition, more CD69, IFN-γ, and GzmB were expressed in the anti-CD19-CAR-T cells. Cell proliferation was also enhanced in both antigen-independent and antigen-dependent manners. Degranulation was also improved as evidenced by an increased level of CD107a. Moreover, the knockdown of ACAT1 led to better anti-tumor efficacy of anti-CD19 CAR-T cells in the B-cell lymphoma mice model. Our study demonstrates novel CAR-T cells containing ACAT1 shRNA with improved efficacy compared to conventional anti-CD19-CAR-T cells in vitro and in vivo. [ABSTRACT FROM AUTHOR]

The interferometric radar altimeter (IRA) is an innovative remote sensing sensor that enables the observation of mesoscale and submesoscale (meso–submesoscale) ocean dynamic phenomena. The charge-neutral atmosphere introduces path delay and bending in signal propagation. In this study, three types of sea surface height (SSH) errors caused by charge-neutral atmosphere propagation path for IRA were identified: differential delay error (DDE), path delay error (PDE), and path bending error (PBE). Among them, DDE exhibits a proportionality to the negative zenith neutral delay (ZND) and demonstrates a significant increase with the incident angle; PDE is solely reliant on the ZND; PBE is like DDE in trend and magnitude resembling a ramp. Intriguingly, PBE exhibits insensitivity to variations in the charge-neutral atmosphere, behaving more like a systematic error. Theoretically, PBE leads to an increase in the SSH error of about 1.2 cm at far range for SWOT. The ZND spectrum fitted from the Jason-3 zenith delay correction data is additionally utilized to simulate the spatial distribution of ZND anomaly within the SWOT observation swaths. Then, the impact of PDE anomaly (PDEA), PBE, and DDE anomaly (DDEA) on the observation performance of SWOT is also considered in conjunction with SSH data provided by HYCOM. The findings indicate that both PDEA and PBE significantly reduce IRA's performance in oceanic phenomena, while the impact of DDEA can be disregarded. The PBE can distort the sea surface trend and increases the mean sea level within the range, requiring further attention. Significance Statement: This paper focuses on how the signal path affects the accuracy of measuring sea surface height (SSH) using the interferometric radar altimeter (IRA) in the charge-neutral atmosphere. The present paper defines three types of SSH errors caused by propagation path to IRA, namely, differential delay error (DDE), path delay error (PDE), and path bending error (PBE). Three types of SSH errors will make a significant impact on the altimetry performance of IRA. Among them, PDE spatial anomaly and PBE will reduce the expected observation performance of the meso–submesoscale ocean phenomena in IRA's swath, while PBE has not received enough attention in previous studies. Therefore, the research will provide a theoretical basis for IRA to correct the above SSH errors. [ABSTRACT FROM AUTHOR]

The impact of ocean surface waves on wind stress at the air–sea interface under low to moderate wind conditions was systematically investigated based on a simple constant flux model and flux measurements obtained from two coastal towers in the East China Sea and South China Sea. It is first revealed that the swell-induced perturbations can reach a height of nearly 30 m above the mean sea surface, and these perturbations disturb the overlying airflow under low wind and strong swell conditions. The wind profiles severely depart from the classical logarithmic profiles, and the deviations increase with the peak wave phase speeds. At wind speeds of less than 4 m s−1, an upward momentum transfer from the wave to the atmosphere is predicted, which is consistent with previous studies. A comparison between the observations and model indicates that the wind stress calculated by the model is largely consistent with the observational wind stress when considering the effects of surface waves, which provides a solution for accurately calculating wind stress in ocean and climate models. Furthermore, the surface waves at the air–sea interface invalidate the traditional Monin–Obukhov similarity theory (MOST), and this invalidity decreases as observational height increases. [ABSTRACT FROM AUTHOR]

The microenvironment of most tumors is complex, comprising numerous aspects of immunosuppression. Several studies have indicated that the adrenergic system is vital for controlling immunological responses. In the context of the tumor microenvironment, nor-adrenaline (NA) is poured in by innervating nerves and tumor tissues itself. The receptors for nor-adrenaline are present on the surfaces of cancer and immune cells and are often involved in the activation of pro-tumoral signaling pathways. Beta2-adrenergic receptors (β2-ARs) are an emerging class of receptors that are capable of modulating the functioning of immune cells. β2-AR is reported to activate regulatory immune cells and inhibit effector immune cells. Blocking β2-AR increases activation, proliferation, and cytokine release of T lymphocytes. Moreover, β2-AR deficiency during metabolic reprogramming of T cells increases mitochondrial membrane potential and biogenesis. In the view of the available research data, the immunosuppressive role of β2-AR in T cells presents it as a targetable checkpoint in CAR-T cell therapies. In this review, we have abridged the contemporary knowledge about adrenergic-stress-mediated β2-AR activation on T lymphocytes inside tumor milieu. [ABSTRACT FROM AUTHOR]

With the rapid development of meteorology, there requires a great need to better forecast dew point temperatures contributing to mild building surface and rational chemical control, while researches on time series forecasting barely catch the attention of meteorology. This paper would employ the seasonal-trend decomposition-based simplified dendritic neuron model (STLDNM*) to predict the dew point temperature. We utilize the seasonal-trend decomposition based on LOESS (STL) to extract three subseries from the original sequence, among which the residual part is considered as an input of an improved dendritic neuron model (DNM*). Then the back-propagation algorithm (BP) is used for training DNM* and the output is added to another two series disposed. Four datasets, which record dew points of four cities, along with eight algorithms are put into the experiments for comparison. Consequently, the combination of STL and simplified DNM achieves the best speed and accuracy. [ABSTRACT FROM AUTHOR]

Background: NK cell is one of innate immune cells and can protect the body from cancer-initiating cells. It has been reported that GPR116 receptor is involved in inflammation and tumors. However, the effect of GPR116 receptor on the NK cells remains largely unclear. Results: We discovered that GPR116−/− mice could efficiently eliminate pancreatic cancer through enhancing the proportion and function of NK cells in tumor. Moreover, the expression of GPR116 receptor was decreased upon the activation of the NK cells. Besides, GPR116−/− NK cells showed higher cytotoxicity and antitumor activity in vitro and in vivo by producing more GzmB and IFNγ than wild-type (WT) NK cells. Mechanistically, GPR116 receptor regulated the function of NK cells via Gαq/HIF1α/NF-κB signaling pathway. Furthermore, downregulation of GPR116 receptor promoted the antitumor activity of NKG2D-CAR-NK92 cells against pancreatic cancer both in vitro and in vivo. Conclusions: Our data indicated that GPR116 receptor had a negatively effect on NK cell function and downregulation of GPR116 receptor in NKG2D-CAR-NK92 cells could enhance the antitumor activity, which provides a new idea to enhance the antitumor efficiency of CAR NK cell therapy. [ABSTRACT FROM AUTHOR]

Compared with co-polarized (HH/VV) normalized radar cross-section (NRCS) backscattered from the sea surface, there is no saturation phenomenon in cross-polarized (HV/VH) NRCS when wind speed is greater than about 20 m/s, so cross-polarized synthetic aperture radar (SAR) images can be used for high wind speed monitoring. In this work, a new geophysical model function (GMF) is proposed to describe the relation of the C-band cross-polarized NRCS with wind speed and radar incidence angle. Here, sixteen ScanSAR wide mode SAR images acquired by RADARSAT-2 (RS-2) under tropical cyclone (TC) conditions and the matching wind speed data from the European Centre for Medium-Range Weather Forecasts (ECMWF) and the Stepped-Frequency Microwave Radiometer (SFMR) are collected and divided into datasets A and B. Dataset A is used for analyzing the effects of the wind field and radar incidence angle on the reference noise-removed cross-polarized NRCS, and for proposing the new GMF for each sub-swath of the SAR images, while dataset B is used to retrieve wind speed and evaluate the validity of the new GMF. The comparisons between the wind speeds retrieved by the new GMF and the collocated ECMWF and SFMR data demonstrate the excellent performance of the new GMF for wind speed retrieval. To analyze the universality of the new GMF, wind speed retrievals based on 32 Sentinel-1A/B (S-1A/B) extra-wide-swath (EW) mode images acquired under TC conditions are also compared with the collocated wind speeds measured by the Soil Moisture Active Passive (SMAP) radiometer, and the retrieved wind speeds have RMSE of 3.667 m/s and a bias of 2.767 m/s. The successful applications in high wind speed retrieval of different tropical cyclones again supports the availability of the new GMF. [ABSTRACT FROM AUTHOR]

The efficacy of CAR-T cell therapy has been hindered by several factors that are intrinsic to the tumor microenvironment. Many strategies are being employed to overcome these barriers and improve immunotherapies efficacy. Interleukin (IL)− 4 is a cytokine released by tumor cells inside the tumor microenvironment and it can oppose T cell effector functions via engagement with the IL-4 receptor on the surface of T cells. To overcome IL-4-mediated immunosuppressive signals, we designed a novel inverted cytokine receptor (ICR). Our novel CAR construct (4/15NKG2D-CAR), consisted of an NKG2D-based chimeric antigen receptor, co-expressing IL-4R as an extracellular domain and IL-15R as a transmembrane and intracellular domain. In this way, IL-4R inhibitory signals were converted into IL-15R activation signals downstream. This strategy increased the efficacy of NKG2D-CAR-T cells in the pancreatic tumor microenvironment in vitro and in vivo. 4/15NKG2D-CAR-T cells exhibited increased activation, degranulation, cytokine release, and cytotoxic ability of NKG2D-CAR-T cells against IL-4+ pancreatic cell lines. Furthermore, 4/15NKG2D-CAR-T cells exhibited more expansion, less exhaustion, and an increased percentage of less differentiated T cell phenotypes in vitro when compared with NKG2D-CAR-T cells. That is why IL-4R/IL-15R-modified CAR-T cells eradicated more tumors in vivo and outperformed NKG2D-CAR-T cells. Thus, we report here a novel NKG2D-CAR-T cells that could overcome IL-4-mediated immunosuppression in solid tumors. [Display omitted] • IL-4R activation inhibits CAR-T cell function. • 4/15-ICR successfully inverted IL-4 negative signals. • 4/15-ICR improved anti-tumor efficacy of CAR-T therapy in vitro and in vivo. [ABSTRACT FROM AUTHOR]

2a-c. Inside the YBH, seawater temperatures ranged from 14.8 to 30.0 °C, and salinities from 33.4 to 34.5 PSU. Previously, the oldest reported seawater in the open ocean was in the deep North Pacific, with ages ranging from 1000 to 1850 a [[10]]; these are much younger than the seawater at the bottom of the YBH. When the water temperature inside the YBH is higher than at the surface, young surface seawater could replace this relatively warm water mass via cooling convection. [Extracted from the article]

Objective: Nutritional factors such as extensively hydrolyzed casein (eHC) have been proposed to exert anti-inflammatory activity and affect clinical outcomes such as tolerance development in cow's milk allergy. Granzyme B (GrB) induces apoptosis in target cells and also controls the inflammatory response. Whether eHC could affect the activity of granzyme B and play a role in GrB-mediated inflammatory responses in vitro was unknown. Methods: The activity of GrB was measured using the substrate Ac-IEPD-pNA. Inflammatory responses were induced with GrB in HCT-8 and THP-1 cells, and pro-inflammatory cytokines were determined at the transcriptional and protein level. Results: GrB could induce the expression of IL-1β in HCT-8 cells, and IL-8 and MCP-1 in THP-1 cells, respectively. Interestingly, GrB acted synergistically on LPS-induced inflammation in HCT-8 cells and eHC reduced pro-inflammatory responses in both GrB and LPS-mediated inflammation. Further analyses revealed that eHC could inhibit the biological activities and cytotoxic activities of GrB and then could reduce GrB-mediated inflammatory response. Conclusion: The results from the current study suggest that anti-inflammatory activity of extensively hydrolyzed casein is, to a certain extent, mediated through modulation of granzyme B activity and responses. [ABSTRACT FROM AUTHOR]

The immunogenicity and efficacy of a DNA vaccine can be greatly enhanced when a gene adjuvant is used. LIGHT, a member of TNF superfamily, can function as a costimulatory molecule for human naïve T cells to proliferate and can be a potential gene adjuvant. In the current study, the eukaryotic expression plasmid pcDNA-nef was constructed by inserting a full-length nef gene into pcDNA3.1(+), and an in vitro transfection experiment suggested that the nef gene could be expressed successfully in mammalian cells. BALB/c mice were immunized with HIV-1 nef DNA vaccine plasmids alone or in combination with LIGHT expression plasmids, and the specific humoral and cellular immune responses were measured. The data showed that HIV-1 nef DNA vaccine plasmids could induce anti-Nef antibodies, Nef-specific lymphocyte proliferation and CTL activity, whereas stronger specific immune responses were induced in mice when co-immunizing with HIV-1 nef DNA vaccine plasmids and LIGHT expression plasmids, suggesting that the eukaryotic expression vector encoding HIV-1 nef is capable of inducing specific immune responses towards HIV-1 Nef and that LIGHT could be considered as a gene adjuvant for HIV-1 DNA vaccination. [ABSTRACT FROM AUTHOR]

Two recombinant plasmids, pUTA2P1 and pUTAL3CP1, were constructed by inserting structural protein precursor P1-2A and proteinase 3C of foot-and-mouth disease virus (FMDV) into fowl-pox virus (FPV) recombinant vectors pUTA-2 and pUTA-16-LacZ respectively, and two recombinant FPVs (vUTA2P1 and vUTAL3CP1) screened by the RT-PCR, IFA assay and Western blotting assay were obtained successfully. Mice injected respectively with rFPVs were induced high level specific anti. FMDV antibodies, increasing of T subtypes, and higher cytotoxicities of splenocytes than those of control groups. These results indicated that a new method was used to construct a potential candidate vaccine of FMDV. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA), a degenerative joint disorder, has been reported as the most common cause of disability worldwide. The production of inflammatory cytokines is the main factor in OA. Previous studies have been reported that obeticholic acid (OCA) and OCA derivatives inhibited the release of proinflammatory cytokines in acute liver failure, but they have not been studied in the progression of OA. In our study, we screened our small synthetic library of OCA derivatives and found T-2054 had anti-inflammatory properties. Meanwhile, the proliferation of RAW 264.7 cells and ATDC5 cells were not affected by T-2054. T-2054 treatment significantly relieved the release of NO, as well as mRNA and protein expression levels of inflammatory cytokines (IL-6, IL-8 and TNF-α) in LPS-induced RAW 264.7 cells. Moreover, T-2054 promoted extracellular matrix (ECM) synthesis in TNF-α-treated ATDC5 chondrocytes. Moreover, T-2054 could relieve the infiltration of inflammatory cells and degeneration of the cartilage matrix and decrease the levels of serum IL-6, IL-8 and TNF-α in DMM-induced C57BL/6 mice models. At the same time, T-2054 showed no obvious toxicity to mice. Mechanistically, T-2054 decreased the extent of p-p65 expression in LPS-induced RAW 264.7 cells and TNF-α-treated ATDC5 chondrocytes. In summary, we showed for the first time that T-2054 effectively reduced the release of inflammatory mediators, as well as promoted extracellular matrix (ECM) synthesis via the NF-κB-signaling pathway. Our findings support the potential use of T-2054 as an effective therapeutic agent for the treatment of OA. [ABSTRACT FROM AUTHOR]

Simple Summary: CD19-targeted chimeric antigen receptor (CAR) T (CD19-CAR-T) cell therapy usually causes B cell aplasia because of "on-target off-tumor" toxicity. The aim of the study was to assess the concept that the introduction of an inhibitory CAR (iCAR) into CAR-T cells could alleviate the side effect of CD19-CAR-T cell therapy. The results showed that CD19-CAR-T cells with a novel KIR (killer inhibitory receptor) /PD-1 (programmed death receptor-1)-based inhibitory CAR (iKP-19-CAR-T) exhibited more naïve, less exhausted phenotypes and preserved a higher proportion of central memory T cells (TCM). Furthermore, iKP-19-CAR-T cells exerted the similar level of cytotoxicity on CD19+HLA-C1− Burkitt's lymphoma cells compared to CD19-CAR-T cells while sparing CD19+HLA-C1+ healthy human B cells both in vitro and in the xenograft model. Our data demonstrates that the KIR/PD-1-based inhibitory CAR can be a promising strategy to avoid B cell aplasia caused by CD19-CAR-T cell therapy. B cell aplasia caused by "on-target off-tumor" toxicity is one of the clinical side effects during CD19-targeted chimeric antigen receptor (CAR) T (CD19-CAR-T) cells treatment for B cell malignancies. Persistent B cell aplasia was observed in all patients with sustained remission, which increased the patients' risk of infection. Some patients even died due to infection. To overcome this challenge, the concept of incorporating an inhibitory CAR (iCAR) into CAR-T cells was introduced to constrain the T cells response once an "on-target off-tumor" event occurred. In this study, we engineered a novel KIR/PD-1-based inhibitory CAR (iKP CAR) by fusing the extracellular domain of killer cell immunoglobulin-like receptors (KIR) 2DL2 (KIR2DL2) and the intracellular domain of PD-1. We also confirmed that iKP CAR could inhibit the CD19 CAR activation signal via the PD-1 domain and CD19-CAR-T cells bearing an iKP CAR (iKP-19-CAR-T) exerted robust cytotoxicity in vitro and antitumor activity in the xenograft model of CD19+HLA-C1− Burkitt's lymphoma parallel to CD19-CAR-T cells, whilst sparing CD19+HLA-C1+ healthy human B cells both in vitro and in the xenograft model. Meanwhile, iKP-19-CAR-T cells exhibited more naïve, less exhausted phenotypes and preserved a higher proportion of central memory T cells (TCM). Our data demonstrates that the KIR/PD-1-based inhibitory CAR can be a promising strategy for preventing B cell aplasia induced by CD19-CAR-T cell therapy. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T-cell therapy is a promising approach in treating solid tumors but the therapeutic effect is limited. Prostate cancer is a typical solid malignancy with invasive property and a highly immunosuppressive microenvironment. Ligands for the NKG2D receptor are primarily expressed on many cancer cells, including prostate cancer. In this study, we utilized NKG2D-based CAR to treat prostate cancer, and improved the therapeutic effect by co-expression of IL-7. The results showed that NKG2D-CAR T cells performed significantly increased cytotoxicity against prostate cancer compared to non-transduced T cells in vitro and in vivo. Moreover, the introduction of the IL-7 gene into the NKG2D-CAR backbone enhanced the production of IL-7 in an antigen-dependent manner. NKG2DIL7-CAR T cells exhibited better antitumor efficacy at 16 h and 72 h in vitro, and inhibited tumor growth in xenograft models more effectively. In mechanism, enhanced proliferation and Bcl-2 expression in CD8+ T cells, decreased apoptosis and exhaustion, and increased less-differentiated cell phenotype may be the reasons for the improved persistence and survival of NKG2DIL7-CAR T cells. In conclusion, these findings demonstrated that NKG2D is a promising option for CAR T-cell therapy on prostate cancer, and IL-7 has enhanced effect on NKG2D-based CAR T-cell immunotherapy, providing a novel adoptive cell therapy for prostate cancer either alone or in combination with IL-7. [ABSTRACT FROM AUTHOR]

Surfactant layers with viscoelastic properties floating on the water surface damp short gravity-capillary waves. Inspired by the known virtue of fish oil to still angry seas, a laboratory study has been made on wind wave generation and on the interaction between wind-waves, paddle-waves and airflow in a tank containing a thin fish oil film uniformly spread on the water surface. According to the Marangoni resonance-type damping mechanism, for oily surfaces the energy dissipation process is quite selective in wavenumbers, but its effects are not, since it spreads (although to a lesser extent) towards longer and shorter waves via nonlinear interactions and modification of the airflow profile. With a thin layer of oil on the surface, it is rather peculiar that in the wind-only condition (no paddle waves) the wave field does not grow from the rest condition. This equilibrium was altered by paddle (longer) waves, the generation and evolution of short waves (in clean water and with oil) being modified by their interaction with the orbital velocity of the longer waves and their effect on the airflow. Paddle waves did grow under the action of wind, how much being similar in clean and oily water conditions, a fact we ascribe to the similar distortion of the wind profile in the two cases. We have also found that wind-supported stress on the oily water surface was able to generate a surface current, whose magnitude turns out to be comparable to the one in clean water. Our results expand previous investigations on the same topic. We stress the benefit of experiments with surfactants to explore in detail the physics at, and the exchanges across, the wavy and no-wavy air-water interface. ReferenceBenetazzo, A., Cavaleri, L., Ma, H., Jiang, S., Bergamasco, F., Jiang, W., Chen, S., and Qiao, F.: Fish oil in a wave tank: a look at the air-water response, Ocean Sci. Discuss., https://doi.org/10.5194/os-2018-111, in review, 2019. [ABSTRACT FROM AUTHOR]