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MAPbBr 3 single crystal is coated with FAPbI 3 film through the half-cladding method, which forms the laterally structured heterojunction. In comparison with pure MAPbBr 3 single crystal, the optoelectronic properties of the heterojunction exhibit a rare dual narrowband detection characteristic located at excitonic absorption of respective MAPbBr 3 and FAPbI 3 due to the different penetration depth of light photodetection. In addition, as the applied bias voltage decreases, the charge collection efficiency at the shorter wavelength range also decreases. The self-power characteristics of the device can be attributed to the existence of the built-in electric field in the heterojunction, achieving a detectivity of 5.38 × 1012 Jones for red light at 0 V. And the fast response time without an external electric field is 6.6 × 10−2 s, which is much shorter than the reported MAPbI 3 /MAPbBr 3 heterojunction photodetector. Our results pave the way for the simple synthesis of MAPbBr 3 /FAPbI 3 heterojunction and their applications in photodiode and a high-performance photodetector with a fast response. [Display omitted] • First reported MAPbBr 3 single crystal coated with FAPbI3 film forms the laterally structured heterojunction. • a rare dual narrowband detection characteristic located at excitonic absorption of respective MAPbBr 3 and FAPbI 3. • Response time without an external electric field is 6.6 × 10−2 s. [ABSTRACT FROM AUTHOR]

In this work, the Pb2+ substitution with Zn2+ in CsPbI 3 perovskite nanocrystals (PNCs) is partially achieved to improve the optoelectronic properties through temperature-pressure assisted crystallization approach. The spectral and dynamic exciton recombination for zinc alloyed CsPbI 3 PNCs are probed with steady-state/time-resolved PL (TRPL), transient absorption (TA) techniques. Compared with pure CsPbI 3 PNCs, PLQY can be boosted to 60% when incorporating the optimal amount of ZnI 2 in the synthesis, and long-term thermal stability are obtained in a series of red-emitting alloyed CsPbI 3 PNCs. Simultaneously, the change of exciton binding energy and average optical phonon energy indicate that weaker nonradiative transition for exciton recombination of zinc alloyed CsPbI 3 PNCs than those of CsPbI 3 PNCs. TRPL and TA spectroscopy are used to understand the photoinduced carrier relaxation processes. The carrier dynamics reveal that the coupling between Zn-induced lowest excited state and exciton trapping state is promoted in zinc alloyed CsPbI 3 PNCs, which can significantly enhance the efficiency of excitonic recombination. The improved performance of PLQY and thermal stability makes these zinc alloyed CsPbI 3 PNCs as appropriate perovskite materials for efficient optoelectronic devices. Image 1 • CsPbI 3 PNCs by Zn incorporation are synthesized by pressure-temperature assisted crystallization method. • The PL properties of pure and zinc alloyed CsPbI 3 PNCs are investigated by various spectroscopic techniques. • The carrier dynamics reveal that the coupling between the Zn-induced lowest excited state and exciton trapping state is promoted in zinc alloyed CsPbI 3 PNCs. [ABSTRACT FROM AUTHOR]

Cs 2 Ag x Na 1-x InCl 6 microcrystals (MCs) are synthesized using a solvothermal method. The regular variation of Na incorporation is characterized according to the intensity change of the X-ray diffraction and ultraviolet visible absorption peaks. Temperature-dependent photoluminescence (PL) properties of Cs 2 Ag x Na 1-x InCl 6 MCs are studied by use of steady-state PL and time-resolved PL (TRPL) measurements. From steady-state PL, it is verified that the white-light emission primarily originates from self-trapped excitons (STEs) at low temperature (80–290 K). When the electron-phonon interactions become stronger, STEs are promoted to generate from free excitons (FEs). And the high temperature-dependent (293–450 K) PL reveals the thermal quenching process. Temperature-dependent TRPL demonstrates that the change of lifetimes is attributed to band-edge FEs state and STEs state. It is found that the electrically-driven PL decreases to 70% then becomes stable from 0 to 120 min when light-emitting diodes (LEDs) are fabricated to explore the thermal stability. Our results suggest these white-emission Cs 2 Ag x Na 1-x InCl 6 MCs can be used as excellent materials for LEDs and provide reference to engineer such MCs toward practical optoelectronic applications. Image 1 • Temperature-dependent photoluminescence are studied to verify the white emission from self-trapped excitons. • Temperature-dependent TRPL demonstrates that the change of lifetimes is due to band-edge free excitons and STEs state. • We fabricated LED to study the stability of electrically-driven PL, indicating better application of this material. [ABSTRACT FROM AUTHOR]

Background: JAK/STAT3 is one of the critical signaling pathways involved in the occurrence and development of hepatocellular carcinoma (HCC). BBI608 (Napabucasin), as a novel small molecule inhibitor of STAT3, has shown previously excellent anti-HCC effects in vitro and in mouse models. However, low bioavailability, high cytotoxicity and other shortcomings limit its clinical application. In this study, PLGA was selected to prepare Napabucasin PLGA nanoparticles (NPs) by solvent evaporation method, overcoming these limitations and improving the passive targeting effect that nanoparticle mediated. Base on this, we systematically evaluated the anti-HCC effect of Napabucasin-PLGA NPs and explored the underlying mechanisms., Methods: Napabucasin-PLGA NPs were prepared by solvent evaporation method. CCK-8 assay, Annexin V/PI double staining, RT-qPCR, colony formation assay, and Western blotting were performed to evaluate the anti-HCC effect of Napabucasin-PLGA NPs in vitro. Proliferation assay and migration assay were used to detect the effects of Napabucasin-PLGA NPs-treated HCC-TAMs on tumor biological characteristics of HCC cells. Flow cytometry was used to detect anti-HCC immune responses induced by Napabucasin-PLGA NPs in vivo., Results: Our results demonstrated that Napabucasin-PLGA NPs could improve the bioavailability of Napabucasin and enhance Napabucasin-mediated the anti-HCC effects in vitro and in vivo with no significant drug toxicity. In addition to the direct inhibitory effects on the tumor biological characteristics of HCC cells, Napabucasin-PLGA NPs could promote the polarization of macrophages from tumor-promoting M2-type to anti-tumor M1-type, improving the tumor immune microenvironment and augmenting T cell-mediated anti-tumor responses. The underlining mechanisms showed Napabucasin-PLGA NPs suppressed the STAT3/FAO signaling axis in HCC-induced tumor-associated macrophages (TAMs)., Conclusions: These findings demonstrated Napabucasin-PLGA NPs is a potential therapeutic candidate for HCC, and provided a new theoretical and experimental basis for further development and clinical application of Napabucasin., Competing Interests: Declarations. Ethics approval and consent to participate: All animal protocols and experiments were approved by the Institutional Animal Care and Use Committee of Shandong University, China, and complied with the Guide for the Care and Use of Laboratory Animals. Consent for publication: All contributing authors agreed to the publication of this article. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

S-scheme Fe 2 O 3 /g-C 3 N 4 heterojunctions were successfully fabricated by the ultrasonic assistance method to remove norfloxacin (NOR) under visible light irradiation. The synthesized catalysts were well studied through various techniques. The obtained Fe 2 O 3 /g-C 3 N 4 heterojunctions exhibited an optimal photocatalytic degradation of 94.7% for NOR, which was 1.67 and 1.28 times higher than using Fe 2 O 3 and g-C 3 N 4 alone, respectively. In addition, the kinetic constant of NOR removal with Fe 2 O 3 /g-C 3 N 4 composites was about 0.6631 h -1 , and NOR photo-deegradation was still 86.7% after four cycles. The enhanced photocatalytic activity may be mainly attributed to the formation of S-scheme Fe 2 O 3 /g-C 3 N 4 heterojunctions with built-in electric fields, which were beneficial to the separation and transfer of photostimulated charge carriers. Furthermore, a possible photo-degradation mechanism of NOR for S-scheme Fe 2 O 3 /g-C 3 N 4 heterojunctions is described.

Tumor malignancy highly depends on the stiffness of tumor matrix, which mainly consists of collagen. Despite the destruction of tumor matrix is conducive to tumor therapy, it causes the risk of tumor metastasis. Here, metal-anesthetic network-coated dormant collagenase-producing Clostridium is constructed to simultaneously destruct tumor matrix and inhibit tumor metastasis. By metal-phenolic complexation and π-π stacking interactions, a Fe 3+ -propofol network is formed on bacterial surface. Coated dormant Clostridium can selectively germinate and rapidly proliferate in tumor sites due to the ability of carried Fe 3+ ions to promote bacterial multiplication. Intratumoral colonization of Clostridium produces sufficient collagenases to degrade tumor collagen mesh and the loaded propofol restrains tumor metastasis by inhibiting tumor cell migration and invasion. Meanwhile, the delivered Fe 3+ ions are reduced to the Fe 2+ form by intracellular glutathione, thereby inducing potent Fenton reaction to trigger lipid peroxidation and ultimate ferroptosis of tumor cells. In addition to a satisfactory safety, a single intratumoral injection of coated dormant Clostridium not only effectively retards the growth of established large primary tumors, but also significantly suppresses distal lung metastasis in two different orthotopic tumor models. This work proposes a strategy to develop advanced therapeutics for malignant tumor treatment and metastasis prevention., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Organic-inorganic metal halides have attracted great attention due to their tunable structural and spectroscopic properties. Here, two organic-inorganic hybrid manganese bromides, (TEMA) 2 MnBr 4 (TEMA = triethylmethylammonium) and (TEBA) 2 MnBr 4 (TEBA = benzyltriethylammonium), are synthesized using the evaporation crystallization method. Following a heat-induced phase transition at 363 K, the structure and optical properties of (TEMA) 2 MnBr 4 change but return to their initial state upon cooling to room temperature, as confirmed by X-ray diffraction, photoluminescence (PL), and Raman spectra. Meanwhile, (TEBA) 2 MnBr 4 , with a larger Mn-Mn distance, exhibits a higher photoluminescence quantum yield of 98.1% and greater thermal quenching temperature. However, due to the poorer thermal stability of the organic cation, the crystal melts at 400 K, leading to fluorescence quenching. White LEDs based on (TEMA) 2 MnBr 4 and (TEBA) 2 MnBr 4 are successfully fabricated with color rendering indices of 97.4 and 97.2, respectively. The investigation provides deep insights into the structural and optical properties of (TEMA) 2 MnBr 4 and (TEBA) 2 MnBr 4 , advancing research for LED display design by tuning organic cations.

Nimodipine, a calcium antagonist, exert beneficial neurovascular protective effects in clinic. Recently, Calcium channel blockers (CCBs) was reported to protect against liver fibrosis in mice, while the exact effects of Nimodipine on liver injury and hepatic fibrosis remain unclear. In this study, we assessed the effect of nimodipine in Thioacetamide (TAA)-induced liver fibrosis mouse model. Then, the collagen deposition and liver inflammation were assessed by HE straining. Also, the frequency and phenotype of NK cells, CD4 + T and CD8 + T cells and MDSC in liver and spleen were analyzed using flow cytometry. Furthermore, activation and apoptosis of primary Hepatic stellate cells (HSCs) and HSC line LX2 were detected using α-SMA staining and TUNEL assay, respectively. We found that nimodipine administration significantly attenuated liver inflammation and fibrosis. And the increase of the numbers of hepatic NK and NKT cells, a reversed CD4 + /CD8 + T ratio, and reduced the numbers of MDSC were observed after nimodipine treatment. Furthermore, nimodipine administration significantly decreased α-SMA expression in liver tissues, and increased TUNEL staining adjacent to hepatic stellate cells. Nimodipine also reduced the proliferation of LX2, and significantly promoted high level of apoptosis in vitro. Moreover, nimodipine downregulated Bcl-2 and Bcl-xl, simultaneously increased expression of JNK, p-JNK, and Caspase-3. Together, nimodipine mediated suppression of growth and fibrogenesis of HSCs may warrant its potential use in the treatment of liver fibrosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Chronic hepatitis B virus (HBV) infection is a global health problem that substantially increases the risk of developing liver disease. The development of a novel strategy to induce anti-HB seroconversion and achieve a long-lasting immune response against chronic HBV infection remains challenging. Here, we found that chronic HBV infection affected the signaling pathway involved in STING-mediated induction of host immune responses in dendritic cells (DCs) and then generated a lymph node-targeted nanovaccine that co-delivered hepatitis B surface antigen (HBsAg) and cyclic diguanylate monophosphate (c-di-GMP) (named the PP-SG nanovaccine). The feasibility and efficiency of the PP-SG nanovaccine for CHB treatment were evaluated in HBV-carrier mice. Serum samples were analyzed for HBsAg, anti-HBs, HBV DNA, and alanine aminotransferase levels, and liver samples were evaluated for HBV DNA and RNA and HBcAg, accompanied by an analysis of HBV-specific cellular and humoral immune responses during PP-SG nanovaccine treatment. The PP-SG nanovaccine increased antigen phagocytosis and DC maturation, efficiently and safely eliminated HBV, achieved a long-lasting immune response against HBV reinjection, and disrupted chronic HBV infection-induced immune tolerance, as characterized by the generation and multifunctionality of HBV-specific CD8 + T and CD4 + T cells and the downregulation of immune checkpoint molecules. HBV-carrier mice immunized with the PP-SG nanovaccine achieved partial anti-HBs seroconversion. The PP-SG nanovaccine can induce sufficient and persistent viral suppression and achieve anti-HBs seroconversion, rendering it a promising vaccine candidate for clinical chronic hepatitis B therapy., (© 2024. The Author(s).)

The development of temperature-sensitive sensors upgraded by poly(N-isopropylacrylamide) (PNIPAM) represents a significant stride in enhancing performance and tailoring thermoresponsiveness. In this study, an array of temperature-responsive electrochemical sensors modified with different PNIPAM-based copolymer films were fabricated via a "coating and grafting" two-step film-forming technique on screen-printed platinum electrodes (SPPEs). Chemical composition, grafting density, equilibrium swelling, surface wettability, surface morphology, amperometric response, cyclic voltammograms, and other properties were evaluated for the modified SPPEs, successively. The modified SPPEs exhibited significant changes in their properties depending on the preparation concentrations, but all the resulting sensors showed excellent stability and repeatability. The modified sensors demonstrated favorable sensitivity to hydrogen peroxide and L-ascorbic acid. Furthermore, notable temperature-induced variations in electrical signals were observed as the electrodes were subjected to temperature fluctuations above and below the lower critical solution temperature (LCST). The ability to reversibly respond to temperature variations, coupled with the tunability of PNIPAM's thermoresponsive properties, opens up new possibilities for the design of sensors that can adapt to changing environments and optimize their performance accordingly.

Immune system imbalances contribute to the pathogenesis of several different diseases, and immunotherapy shows great therapeutic efficacy against tumours and infectious diseases with immune-mediated derivations. In recent years, molecules targeting the programmed cell death protein 1 (PD-1) immune checkpoint have attracted much attention, and related signalling pathways have been studied clearly. At present, several inhibitors and antibodies targeting PD-1 have been utilized as anti-tumour therapies. However, increasing evidence indicates that PD-1 blockade also has different degrees of adverse side effects, and these new explorations into the therapeutic safety of PD-1 inhibitors contribute to the emerging concept that immune normalization, rather than immune enhancement, is the ultimate goal of disease treatment. In this review, we summarize recent advancements in PD-1 research with regard to immune normalization and targeted therapy., (© 2024 John Wiley & Sons Ltd.)

Synergistic phototherapy stands for superior treatment prospects than a single phototherapeutic modality. However, the combined photosensitizers often suffer from incompatible excitation mode, limited irradiation penetration depth, and lack of specificity. We describe the development of upconversion dual-photosensitizer-expressing bacteria (UDPB) for near-infrared monochromatically excitable combination phototherapy. UDPB are prepared by integrating genetic engineering and surface modification, in which bacteria are encoded to simultaneously express photothermal melanin and phototoxic KillerRed protein and the surface primary amino groups are derived to free thiols for biorthogonal conjugation of upconversion nanoparticles. UDPB exhibit a near-infrared monochromatic irradiation-mediated dual-activation characteristic as the photothermal conversion of melanin can be initiated directly, while the photodynamic effect of KillerRed can be stimulated indirectly by upconverted visible light emission. UDPB also show living features to colonize hypoxic lesion sites and inhibit pathogens via bacterial community competition. In two murine models of solid tumor and skin wound infection, UDPB separately induce robust antitumor response and a rapid wound healing effect.

Currently, the alteration of external factors during crude oil extraction easily disrupts the thermodynamic equilibrium of asphaltene, resulting in the continuous flocculation and deposition of asphaltene molecules in crude oil. This accumulation within the pores of reservoir rocks obstructs the pore throat, hindering the efficient extraction of oil and gas, and consequently, affecting the recovery of oil and gas resources. Therefore, it is crucial to investigate the principles of asphaltene deposition inhibition and the synthesis of asphaltene inhibitors. In recent years, the development of nanotechnology has garnered significant attention due to its unique surface and volume effects. Nanoparticles possess a large specific surface area, high adsorption capacity, and excellent suspension and catalytic abilities, exhibiting unparalleled advantages compared with traditional organic asphaltene inhibitors, such as sodium dodecyl benzene sulfonate and salicylic acid. At present, there are three primary types of nanoparticle inhibitors: metal oxide nanoparticles, organic nanoparticles, and inorganic nonmetal nanoparticles. This paper reviews the recent advancements and application challenges of nanoparticle asphaltene deposition inhibition technology based on the mechanism of asphaltene deposition and nano-inhibitors. The aim was to provide insights for ongoing research in this field and to identify potential future research directions.

Here we report on the development and comprehensive evaluations of an mRNA vaccine for chronic hepatitis B (CHB) treatment. In two different HBV carrier mouse models generated by viral vector-mediated HBV transfection (pAAV-HBV1.2 and rAAV8-HBV1.3), this vaccine demonstrates sufficient and persistent virological suppression, and robust immunogenicity in terms of induction of strong innate immune activation, high-level virus-specific antibodies, memory B cells and T cells. mRNA platform therefore holds prospects for therapeutic vaccine development to combat CHB., (© 2024. The Author(s).)

The genus Apium, belonging to the family Apiaceae, comprises roughly 20 species. Only two species, Apium graveolens and Apium leptophyllum, are available in China and are both rich in nutrients and have favorable medicinal properties. However, the lack of genomic data has severely constrained the study of genetics and evolution in Apium plants. In this study, Illumina NovaSeq 6000 and Nanopore sequencing platforms were employed to identify the mitochondrial genomes of A. graveolens and A. leptophyllum . The complete lengths of the mitochondrial genomes of A. graveolens and A. leptophyllum were 263,017 bp and 260,164 bp, respectively, and contained 39 and 36 protein-coding genes, five and six rRNA genes, and 19 and 20 tRNA genes. Consistent with most angiosperms, both A. graveolens and A. leptophyllum showed a preference for codons encoding leucine (Leu). In the mitochondrial genome of A. graveolens , 335 SSRs were detected, which is higher than the 196 SSRs found in the mitochondrial genome of A. leptophyllum . Studies have shown that the most common RNA editing type is C-to-U, but, in our study, both A. graveolens and A. leptophyllum exhibited the U-C editing type. Furthermore, the transfer of the mitochondrial genomes of A. graveolens and A. leptophyllum into the chloroplast genomes revealed homologous sequences, accounting for 8.14% and 4.89% of the mitochondrial genome, respectively. Lastly, in comparing the mitochondrial genomes of 29 species, it was found that A. graveolens , A. leptophyllum , and Daucus carota form a sister group with a support rate of 100%. Overall, this investigation furnishes extensive insights into the mitochondrial genomes of A. graveolens and A. leptophyllum , thereby enhancing comprehension of the traits and evolutionary patterns within the Apium genus. Additionally, it offers supplementary data for evolutionary and comparative genomic analyses of other species within the Apiaceae family.

Edaravone (EDA), a strong novel free radical scavenger, have been demonstrated to exert neurovascular protective effects clinically. Furthermore, EDA can suppress the lung injury, pulmonary fibrosis and skin fibrosis, while the precise effects and mechanisms of EDA on liver injury and fibrosis remain unclear. The effects of EDA on the Thioacetamide (TAA)-induced liver fibrosis were evaluated by sirius red staining, α-SMA immunohistochemistry. The percentages of immune cell subsets were analyzed by flow cytometry. Immunofluorescence assay was performed to identify the fibrotic properties of hepatic stellate cells (HSCs). Western blot and qPCR were used to detect the levels of liver fibrosis-related molecules and IL-1β. EDA displayed a hepatic protective role in TAA-induced chronic liver fibrosis via inhibiting monocyte/macrophages recruitment and IL-1β production of macrophages. Mechanically, EDA inhibited of NF-κB signal pathway and reactive oxygen species (ROS) production in macrophages. Moreover, EDA treatment indirectly suppressed the activation of HSCs by decreasing the IL-1β secretion of macrophages. Together, EDA protects against TAA-induced liver fibrosis via decreasing the IL-1β production of macrophages, thereby providing a feasible solution for clinical treatment of liver fibrosis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Qiuju Han reports was provided by National Natural Science Foundation of China., (Copyright © 2022. Published by Elsevier B.V.)

Chronic hepatitis B (CHB) infection remains a serious public health problem worldwide; however, the relationship between cholesterol levels and CHB remains unclear. We isolated peripheral blood mononuclear cells from healthy blood donors and CHB patients to analyze free cholesterol levels, lipid raft formation, and cholesterol metabolism-related pathways. Hepatitis B virus (HBV)-carrier mice were generated and used to confirm changes in cholesterol metabolism and cell-surface lipid raft formation in dendritic cells (DCs) in the context of CHB. Additionally, HBV-carrier mice were immunized with a recombinant HBV vaccine (rHBVvac) combined with lipophilic statins and evaluated for vaccine efficacy against HBV. Serum samples were analyzed for HBsAg, anti-HBs, and alanine aminotransferase levels, and liver samples were evaluated for HBV DNA and RNA and HBcAg. CHB reduced free cholesterol levels and suppressed lipid raft formation on DCs in patients with CHB and HBV-carrier mice, whereas administration of lipophilic statins promoted free cholesterol accumulation and restored lipid rafts on DCs accompanied by an enhanced antigen-presentation ability in vitro and in vivo. Cholesterol accumulation on DCs improved the rHBVvac-mediated elimination of serum HBV DNA and intrahepatic HBV DNA, HBV RNA, and HBcAg and promoted the rHBVvac-mediated generation and polyfunctionality of HBV-specific CD11a hi CD8α lo cells, induction of the development of memory responses against HBV reinfection, and seroconversion from HBsAg to anti-HBs. The results demonstrated the important role of cholesterol levels in DC dysfunction during CHB, suggesting that strategies to increase cholesterol accumulation on DCs might enhance therapeutic vaccine efficacy against HBV and support development toward clinical CHB treatment., (© 2022. The Author(s), under exclusive licence to CSI and USTC.)

Sorafenib is the first-line treatment for advanced hepatocellular carcinoma (HCC). However, it is difficult to alleviate this disease process using single-agent chemotherapy. Using combination therapies for advanced HCC has become a major trend. Given that STAT3 overexpression is involved in chemotherapy resistance and the immune escape of HCC cells, it has become a potential therapeutic target for HCC in recent years. GEO database analysis showed that STAT3 levels in tumor tissues from non-responders were significantly higher than those in responders to sorafenib. Our studies demonstrated that STAT3 knockdown promoted sorafenib-induced ER stress-induced apoptosis. Importantly, the DNA released by dead HCC cells stimulated the cGAS-STING signaling pathway in CD103 + DCs and promoted type I interferon production, thus, enhancing the anti-tumor function of CD8 + T and NK cells. In conclusion, our results revealed that the combination strategy of sorafenib and STAT3 knockdown might be a potential treatment strategy for HCC, directly and efficiently disturbing the tumor features of HCC cells while improving the tumor microenvironment via the cGAS-STING-Type I IFNs axis of DCs, inducing anti-HCC immune responses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this study., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Benefiting from the easily adjustable optical properties of perovskite, CsPbBr 3 nanocrystals (NCs) are considered to show their advantages in the field of display. Here, we report that a selective laser irradiation is used to induce CsPbBr 3 nanostructural reshaping and then yielding a morphological change. Under 360 or 405 nm laser irradiation, a hierarchical crystal growth process occurs for the fabricated CsPbBr 3 nanoplatelets (NPLs), which are first arranged in a side-by-side manner and reshaped into nanorods (NRs), and then NRs are arranged in the face-to-face manner to reshape into NCs. The entire process is monitored optically and microscopically, which showed that crystal growth relies on seeking a dynamic balance between heat dissipation and accumulation under laser irradiation. The heat on NPLs generated by laser irradiation dissipated with a low dissipation rate and thus led to temperature rising and lattice breaking, which turned out to be the driving force for the crystal growth in CsPbBr 3 NPLs. This feasible laser irradiation-assisted method provides for crystal growth a reliable and scalable route toward the preparation of perovskite functional materials.

In this Letter, erbium (Er 3+ ) and ytterbium (Yb 3+ ) codoped perovskite Cs 2 Ag 0.6 Na 0.4 In 0.9 Bi 0.1 Cl 6 microcrystal (MC) is synthesized and demonstrated systematically to the most prospective optical temperature sensing materials. A dual-mode thermometry based on fluorescence intensity ratio and fluorescence lifetime provides a self-reference and highly sensitive temperature measurement under dual wavelength excitation at a temperature from 300 to 470 K. Combined with the white-light emission derived from self-trapped excitons (STEs), the characteristic emission peak of Er 3+ ions can be observed under 405 nm laser excitation. The fluorescence intensity ratio (FIR) between perovskite and Er 3+ is used as temperature-dependent probe signal, of which maximum value for relative and absolute sensitivities reaches to 1.40% K -1 and 8.20 × 10 -2 K -1 . Moreover, Er 3+ luminescence becomes stronger with the feeding Yb 3+ increasing under 980 nm laser excitation. The energy transfer of Er 3+ and Yb 3+ is revealed by power-dependent photoluminescence (PL) spectroscopy, and the involved upconversion mechanism pertains to the two-photon excitation process. The results reveal that the Er 3+ /Yb 3+ codoped lead-free double perovskite MC is a good candidate for a thermometric material for the novel dual-mode design.

Objective: To investigate the potential miRNA targeting FGF18, and its role in regulating the proliferation, apoptosis and inflammation in human primary chondrocytes., Methods: The normal human chondrocytes were induced by IL-1β to mimic OA in vitro . qPCR and Western blotting were performed to evaluate the expression of FGF18. Target Scan analysis was performed to predict the miRNA targeting FGF18. Then, the expression of miR-590-5p was quantified by qPCR in IL-1β-induced chondrocytes. After transfection of miR-590-5p mimics or inhibitors, CCK-8 assay was conducted to determine the cell viability and apoptosis-related proteins, and cartilage degeneration related biomarkers were assayed by qPCR and Western blotting. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 were determined by ELISA. The targeting relationship between miR-590-5p and FGF18 was assayed by luciferase reporter assay in IL-1β-induced chondrocytes., Results: Target Scan analysis predicted that FGF18 is directly targeted by miR-590-5p. miR-590-5p was up-regulated, whereas FGF18 expression was inhibited in IL-1β-induced chondrocytes. miR-590-5p mimics reduced the expression of FGF18 protein, inhibited the cell viability of chondrocytes, and promoted secretion of inflammatory factors in chondrocytes, while miR-590-5p inhibitors increased FGF18 levels in IL-1β-treated chondrocytes. Furthermore, expression of inflammatory factors in chondrocytes was reduced by miR-590-5p inhibitors. The luciferase reporter assay showed that miR-590-5p could target FGF18., Conclusions: miR-590-5p promotes OA progression by targeting FGF18, which serves as a potential therapeutic target for OA., Competing Interests: None., (AJTR Copyright © 2021.)

Background: Tumour-associated macrophages (TAMs) in the tumour microenvironment (TME) can promote the progression of hepatocellular carcinoma (HCC). Some tumours can be suppressed by targeting Wnt2b in tumour cells. However, the role of Wnt2b in HCC is still unknown. In particular, the role of Wnt2b-mediated signal activation in macrophage polarization in the HCC microenvironment, and the regulatory effect between Wnt and glycolysis in TAMs has not been described., Methods: The expression of Wnt2b in TAMs was detected by qPCR and immunofluorescence. Wnt2b/β-catenin interference in HCC-TAMs was performed by lentivirus carrying targeted shRNA or TLR9 agonist. Markers related to macrophage polarization and the changes of key glycolytic enzymes expression were detected by flow cytometry and qPCR. ECAR was analysed by Seahorse analyser. MTT assay, wound healing assay, western blotting were used to evaluate the promoting effect of different HCC-TAMs on the proliferation, migration and EMT of HCC in vitro. Tumour cells and different HCC-TAMs were injected via subcutaneously into immunodeficient mice to assess the effects of CpG ODN, Wnt2b, or β-catenin on HCC-TAMs in tumour growth in vivo., Results: Polarization-promoting factors derived from HCC cells upregulated the expression of Wnt2b in macrophages, which promoted the polarization of TAMs to M2-like macrophages by activating Wnt2b/β-catenin/c-Myc signalling. Furthermore, this process was associated with the activation of glycolysis in HCC-TAMs. These HCC-TAMs could promote the development of EMT, proliferation, and migration of HCC. In addition to silencing Wnt2b or β-catenin expression, TLR9 agonist CpG ODN downregulated the level of glycolysis and inhibited the M2 polarization of HCC-TAMs, reversing the tumour-promoting effects of TAMs in vitro and vivo., Conclusions: As a potential target for HCC therapy, Wnt2b may play an important regulatory role for the functions of TAMs in the TME. Moreover, the TLR9 agonist CpG ODN might act as a Wnt2b signal inhibitor and can potentially be employed for HCC therapy by disturbing Wnt2b/β-catenin/c-Myc and inhibiting glycolysis in HCC-TAMs.

Tumors can be classified as cold or hot according to the degree of immune cell infiltration into tumor tissues; cold tumors are insensitive to either chemotherapy or immunotherapy and are associated with poor prognosis. Recent studies have shown that STAT3 signaling molecules hinder the conversion of cold to hot tumors by regulating immunosuppressive molecule secretion and immunosuppressive cell functions. This review aims to present the most recent studies on how STAT3 regulates cold tumor formation and discuss its research status in cancer therapy. We also present insight for designing new therapeutic strategies to "heat" tumors and provide a reference for tumor immunotherapy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Cs 4 PbBr 6 /CsPbBr 3 perovskite composites are fabricated by room-temperature one-pot mixing synthesis, which is short in time, free from inert gases and delivers a high product yield. Temperature-dependent photoluminescence shows that a larger exciton binding energy of 291.1 meV exhibits better thermal stability compared with that of pure Cs 4 PbBr 6 and CsPbBr 3 materials. The CIE chromaticity coordinates (0.1380, 0.7236) of green LEDs designed with Cs 4 PbBr 6 /CsPbBr 3 perovskite composites show almost no variation under driving current changing from 5 to 30 mA. Furthermore, the ground Cs 4 PbBr 6 /CsPbBr 3 perovskite composites mixed with red emitting K 2 SiF 6 :Mn 4+ phosphor are dropped and casted on a blue-emitting InGaN chip. The white light emitting diodes (WLEDs) are presented, which have good luminous efficiency of 65.33 lm W -1 at 20 mA, a correlated color temperature of 5190 K, and the white gamut with chromaticity coordinate of (0.3392, 0.3336). According to the state of art, these excellent characteristics observed are much superior to the reported results of conventional perovskite-based WLEDs, which demonstrate the immense potential and great prospect of Cs 4 PbBr 6 /CsPbBr 3 perovskite composites to replace conventional phosphors in lighting devices., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Here, Cs 4 PbBr 6 microcrystals (MCs) are synthesized using a two-phase liquid-liquid immiscible method. In order to unravel the bright green photoluminescence (PL) mechanism for in-situ Cs 4 PbBr 6 MCs, the thermal stability of PL spectra for the supernatant and precipitate of reactants is investigated comparatively. Exciton binding energy, exciton-phonon (EP) coefficient and PL lifetime all indicate that the PL of the precipitate has similar temperature dependence as that of the supernatant. It is found that, according to its structural and optical characteristics, the supernatant of the reactants is CsPbBr 3 nanocrystals (NCs). We also find that the bright green PL from the precipitate of the reactants is due to CsPbBr 3 NCs embedded into Cs 4 PbBr 6 MCs. Experimental results further reveal the size of CsPbBr 3 NCs embedded into Cs 4 PbBr 6 MCs is larger than that of CsPbBr 3 NCs in the supernatant. The surface passivation of the composites can thus help to suppress the thermal quenching of PL for CsPbBr 3 NCs, which opens a new avenue for enhancing the thermal stability of PL for perovskite NCs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

RNA with 5'-triphosphate (3p-RNA) is recognized by RNA sensor RIG-I (retinoic acid-inducible gene I protein). Previously, we reported that small interfering RNA targeting HBx (3p-siHBx) could confer potent anti-hepatitis B virus (HBV) efficacy via HBx silencing and RIG-I activation. However, the characteristics of innate and adaptive immunity especially exhaustion profiles in the liver microenvironment in response to 3p-siHBx therapy have not been fully elucidated. Here, we observed that 3p-siHBx more significantly inhibited HBV replication in vivo. 3p-siHBx enhanced natural killer (NK) cell activation with KLRG1 and CD69 upregulation and interferon (IFN)-γ secretion. 3p-siHBx significantly reversed the exhaustion phenotype of CD8 + T cells, and augmented CD8 + T cell activation and function. Importantly, 3p-siHBx disrupted the differentiation of myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg), accompanied by the reduction of the immunosuppressive cytokines interleukin (IL)-10 and transforming growth factor (TGF)-β. 3p-siHBx also enhanced dendritic cell maturation. Further investigation showed that RIG-I was involved in 3p-siHBx-induced IFN-α, IFN-β, and IFN-λ production. Moreover, RIG-I activation in HBV + hepatocytes would improve the recruitment of CD8 + T cells and NK cells. These results reveal that 3p-siHBx therapy can improve the immune microenvironment in HBV-carrier liver and inhibit HBV replication, indicating the potential utility of RIG-I ligands as molecular adjuvants for viral vaccines or candidate drugs., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The HMBOX1 (Homeobox Containing 1) gene was first isolated from the human pancreatic cDNA libraries and is widely expressed in many tissues. Previously, we detected high expression of HMBOX1 in the liver, but its function was unclear. In this study, hepatocyte-specific HMBOX1 knockout mice (Hm △hep mice) were generated and used to characterize the function of HMBOX1 in the LPS/D-GalN-induced acute liver failure model. HMBOX1-knockout exhibits exacerbated liver injury induced by LPS/D-GalN, accompanied with high levels of inflammatory cytokines both in the liver and in circulation. Further investigation demonstrated that HMBOX1 negatively regulates NF-κB signal transduction. Therefore, HMBOX1-knockout in hepatocytes promotes CCL2 expression through the activation of NF-κB signaling, which enhanced the infiltration of macrophages into the liver. In addition, the decrease of HMBOX1 in hepatocytes promotes the activation of macrophages, upregulating CD80 and MHCⅡ, as well as inflammatory factors TNF-α and IL-6. Importantly, overexpression of HMBOX1 rescued liver injury in Hm △hep mice. These findings indicate that HMBOX1 in hepatocytes acts as a key immunosuppressive factor for inflammation and plays a critical protective role in LPS/D-GalN-induced liver injury., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Hepatitis B virus (HBV) infection is a severe threat to public health, which can be prevented by prophylactic vaccination. Here, we tested nanogels carriers in the prophylactic effect of hepatitis B surface antigen (HBsAg) vaccine. HBsAg nanogels (Ng) were prepared using chitosan (CS) and poly-γ-glutamic acid (γ-PGA). Positively charged Ng (+) and negatively charged Ng (-) were prepared by adjusting the CS and γ-PGA proportion. Dendritic cells (DCs) maturation in mice immunized with HBsAg Ng (+) and HBsAg Ng (-) could be augmented in response to pAAV/HBV1.2 plasmid challenge. Single-dose immunization with HBsAg Ng (+) induced HBsAg specific-antibodies. HBsAg Ng (+) immunized mice cleared HBsAg and restored anti-HBs production after pAAV/HBV1.2 plasmid challenge. Single-dose HBsAg Ng (+) induced humoral and cellular immunity, and could induce effector memory T cells. Single-dose HBsAg Ng (-) favored the induction of cellular immunity, and induced central memory T cells and effector memory T cells. However, HBsAg elimination was similar between HBsAg Ng (+)- and HBsAg Ng (+) plus HBsAg Ng (-)-immunized mice. Zeta potential measurements showed that HBsAg Ng (+) were more stable than HBsAg Ng (-). Therefore, Ng (+) are desirable HBsAg prophylactic vaccine carriers, providing long-term protection against HBV, and are a good choice to study and apply weakly immunostimulatory antigens., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Evidence suggests that exosomes can transfer genetic material between cells. However, their roles in hepatitis B virus (HBV) infection remain unclear. Here, we report that exosomes present in the sera of chronic hepatitis B (CHB) patients contained both HBV nucleic acids and HBV proteins, and transferred HBV to hepatocytes in an active manner. Notably, HBV nucleic acids were detected in natural killer (NK) cells from both CHB patients and healthy donors after exposure to HBV-positive exosomes. Through real-time fluorescence microscopy and flow cytometry, 1,1'-dioctadecyl-3,3,3',3',-tetramethylindodicarbocyanine, 4-chlorobenzenesulfnate salt (DiD)-labeled exosomes were observed to interact with NK cells and to be taken up by NK cells, which was enhanced by transforming growth factor-β treatment. Furthermore, HBV-positive exosomes impaired NK-cell functions, including interferon (IFN)-γ production, cytolytic activity, NK-cell proliferation and survival, as well as the responsiveness of the cells to poly (I:C) stimulation. HBV infection suppressed the expression of pattern-recognition receptors, especially retinoic acid inducible gene I (RIG-I), on NK cells, resulting in the dampening of the nuclear factor κB(NF-κB) and p38 mitogen-activated protein kinase pathways. Our results highlight a previously unappreciated role of exosomes in HBV transmission and NK-cell dysfunction during CHB infection.

Background & Aims: Hepatitis B virus (HBV) has developed strategies to evade immune responses. However, the mechanisms involved remain unclear. The NLRP3 inflammasome plays crucial roles in antiviral host defense and its downstream factor IL-1β has been shown to inhibit HBV infection in vivo. This study aims to assess whether HBV can affect the NLRP3 inflammasome signaling pathways and shed light on the underlying mechanisms HBV utilizes to evade host innate immune responses., Methods: HBV inhibition of the lipopolysaccharide (LPS)-induced NLRP3 inflammasome activation was evaluated by Western blot, quantitative RT-PCR, flow cytometry and immunofluorescence., Results: Kupffer cells expressed significantly more NLRP3 and IL-1β after LPS stimulation; whereas, chronic HBV infection suppressed LPS-induced NLRP3 and pro-IL-1β expression as well as IL-1β maturation. This inhibitory activity is mediated by HBeAg, and is involved in the inhibition of NF-κB signal pathway and reactive oxygen species (ROS) production. The inhibitory effect of HBeAg was confirmed in patients with chronic hepatitis B (CHB) and hepatocellular carcinoma by comparing the levels of IL-1β and NLRP3-related proteins in para-carcinoma tissues from HBeAg-positive or negative patients. Moreover, chronic HBV infection increases the susceptibility of mice to S. typhimurium infection, possibly via inhibiting the NLRP3 inflammasome activation and IL-1β production., Conclusions: HBeAg inhibits LPS-induced NLRP3 inflammasome activation and IL-1β production via suppressing NF-κB pathway and ROS production. This finding provides a novel mechanism for HBV-mediated suppression of innate immune responses, and identifies new therapeutic targets for chronic HBV infection and related diseases., Lay Summary: HBeAg suppresses LPS-induced NLRP3 inflammasome activation and IL-1β production in two ways, one is to repress NLRP3 and pro-IL-1β expression via inhibiting NF-κB phosphorylation, and the other is to repress caspase-1 activation and IL-1β maturation via inhibiting ROS production. This effect contributes to the HBV persistence and immune tolerance., (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

An inadequate immune response of the host is thought to be a critical factor causing chronic hepatitis B virus (CHB) infection. Natural killer (NK) cells, as one of the key players in the eradication and control of viral infections, were functionally impaired in CHB patients, which might contribute to viral persistence. Here, we reported that HBV antigens HBsAg and HBeAg directly inhibited NK cell function. HBsAg and/or HBeAg blocked NK cell activation, cytokine production and cytotoxic granule release in human NK cell-line NK-92 cells, which might be related to the downregulation of activating receptors and upregulation of inhibitory receptor. Furthermore, the underlying mechanisms likely involved the suppression of STAT1, NF-κB and p38 MAPK pathways. These findings implicated that HBV antigen-mediated inhibition of NK cells might be an efficient strategy for HBV evasion, targeting the early antiviral responses mediated by NK cells and resulting in the establishment of chronic virus infection. Therefore, this study revealed the relationship between viral antigens and human immune function, especially a potential important interaction between HBV and innate immune responses., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Toll-like receptors (TLRs) can be expressed by tumor cells, and each TLR exhibits different biological functions. Evidences showed the activation of some certain TLRs could promote tumor progression. One of which TLR4 has been found to promote hepatocellular carcinoma (HCC) cells proliferation, but the detailed mechanism is still unknown. In the present study, we verified that TLR4 was functionally expressed on HCC cells, and TLR4 agonist lipopolysaccharide (LPS) could stimulate the proliferation and clone formation of HCC cells. Most importantly, we found a COX-2/PGE 2 /STAT3 positive feedback loop exists in HCC cells, which could be provoked by TLR4 activation. Consistently, the expression of TLR4, COX-2 and p-STAT3 Y705 was positively correlated with each other in liver tumor tissues from patients with primary HCC. Further investigation demonstrated this loop played a dominant role in TLR4-induced HCC cell proliferation and multidrug resistance (MDR) to chemotherapy. Inhibition of TLR4 or COX-2/PGE 2 /STAT3 loop would attenuate LPS-induced inflammation and proliferation of HCC cells, and enhance the sensitivity of HCC cells to chemotherapeutics in vitro. By using a primary HCC model, we observed COX-2/PGE 2 /STAT3 loop was significantly blocked in TLR4 -/- mice compared to wild type mice, and there was no obvious tumorgenesis sign in TLR4 -/- mice. Therefore, these findings provided the precise molecular mechanism of TLR4 signaling pathway involved in HCC progress, and suggested that TLR4 may be a promising target for HCC treatment.