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The abscisic acid (ABA) receptor PYR/PYL/RCAR, located upstream of the ABA signaling pathway, recognizes ABA signals and initiates the primary process of signal transduction. In our previous study, we found that the PYL4 gene in tomato plants was significantly upregulated after exogenous treatment with the hormone ABA. The present study used virus-induced gene silencing (VIGS) to further elucidate the role of the PYL4 gene in response to drought in tomato (Solanum lycopersicum) plants. Under the drought treatment, the SlPYL4-silenced plants wilted faster than the control plants did. Physiological indicators showed that the total reactive oxygen species (ROS) content and superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) activities of the SlPYL4-silenced plants were lower than those of the control plants after 3 and 6 h of drought stress treatment. After 3 h of drought treatment, hydrogen peroxide (H2O2) and superoxide anion (O2−.) accumulated much more in the leaves of the SlPYL4-silenced plants than in the leaves of the control plants. These results indicated that PYL4 plays a positive role in drought tolerance in tomato plants. Our results also suggest that SlPYL4 is located upstream of the ABA pathway to regulate the expression of PP2C, SnRK, and AREB/ABF genes.

ZFP91 positively regulates IL-1β production in macrophages and may be a potential therapeutic target to treat inflammatory-related diseases. We investigated whether this process is modulated by convallatoxin, which is a cardiac glycoside isolated from the traditional Chinese medicinal plant Adonis amurensis Regel et Radde.In vitro, the mechanisms by which convallatoxin inhibits ZFP91-regulated IL-1β expression were investigated using molecular docking, western blotting, RT-PCR, ELISA, immunofluorescence and immunoprecipitation assays.In vivo, mice liver injury was induced by an intraperitoneal injection of D-GalN and LPS, colitis was induced by oral administration of dextran sulfate sodium (DSS) in drinking water and peritonitis was induced by an intraperitoneal injection of alum.We confirmed that convallatoxin inhibited the release of IL-1β by down-regulating ZFP91. Importantly, we found that convallatoxin significantly reduced K63-linked polyubiquitination of pro-IL-1β regulated by ZFP91 and decreased the efficacy of pro-IL-1β cleavage. Moreover, convallatoxin suppressed ZFP91-mediated activation of the non-canonical cysteine-requiring aspartate protease-8 (caspase-8) inflammasome and MAPK signalling pathways in macrophages. Furthermore, we showed that ZFP91 promoted the assembly of the caspase-8 inflammasome complex, whereas convallatoxin treatment reversed this result. Mice in vivo studies further demonstrated that convallatoxin ameliorated D-GalN/LPS-induced liver injury, DSS-induced colitis and alum-induced peritonitis by down-regulating ZFP91.We show for the first time that convallatoxin-mediated inhibition of ZFP91 is an important regulatory event that prevents inappropriate inflammatory responses to maintain immune homeostasis. This mechanism provides new insight for the development of convallatoxin as a novel anti-inflammatory drug targeting ZFP91.This article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc.

Continuous increase in CO2 emissions results in global warming, thus causing harm to human health and ecosystem. Although many studies investigated the impacts of CO2, how to quantify and analyze them in different regions is a key problem that needs to be solved. Based on the popular ReCiPe 2016 model for life cycle assessment, ReCiPe-Carbon-in-China (RC) model, an evaluation model suitable for quantifying the harm caused by CO2 in China, was established. In RC model, the impact of temperature rise on ischemic heart disease and stroke was quantified, and a new model was constructed to quantify the impact of inland floods caused by temperature rise on human health. The results show that compared with that of ReCiPe 2016 model, the maximum range value of perspectives of RC model in terms of human health dropped from 297% to 47%, and the harm caused by CO2 to human health and ecosystem reduced significantly. These results are in line with China's actual condition. As a carbon-intensive industry, the cement clinker production was analyzed integratively with life cycle assessment theory to verify the effectiveness of RC model, and several optimized measures were put forward to reduce CO2 emissions for a more sustainable cement clinker production.

Germline heterozygous gain-of-function (GOF) mutation of NFKBIA, encoding IκBα, would affect the activation of NF-κB pathway and cause an autosomal dominant (AD) form of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID). Here we reported a Chinese patient with a heterozygous N-terminal truncation mutation of NFKBIA/IκBα, she presented recurrent fever, infectious pneumonia and chronic diarrhea with EDA-ID. Impaired NF-κB translocation and IL1R and TLR4 pathway activation were revealed in this patient. The findings suggested that the truncation mutation of IκBα caused medium impaired of activation of NF-κB but the early death. Furthermore, we reviewed all the reported patients with NFKBIA mutation to learn more about this disease.

Oxidative stress inflicts mitochondrial dysfunction, which has been recognized as a key driver of intestinal diseases. Resveratrol (RSV) and its derivative pterostilbene (PTS) are natural antioxidants and exert a protective influence on intestinal health. However, the therapeutic effects and mechanisms of RSV and PTS on oxidative stress-induced mitochondrial dysfunction and intestinal injury remain unclear. The present study used porcine and cellular settings to compare the effects of RSV and PTS on mitochondrial redox homeostasis and function to alleviate oxidative stress-induced intestinal injury. Our results indicated that PTS was more potent than RSV in reducing oxidative stress, maintaining intestinal integrity, and preserving the mitochondrial function of diquat-challenged piglets. In the in vitro study, RSV and PTS protected against hydrogen peroxide (H2O2)-induced mitochondrial dysfunction in intestinal porcine enterocyte cell line (IPEC-J2) by facilitating mitochondrial biogenesis and increasing the activities of mitochondrial complexes. In addition, both RSV and PTS efficiently mitigated mitochondrial oxidative stress by increasing sirtuin 3 protein expression and the deacetylation of superoxide dismutase 2 and peroxiredoxin 3 in H2O2-exposed IPEC-J2 cells. Furthermore, RSV and PTS preserved mitochondrial membrane potential, which restrained the release of cytochrome C from mitochondria to the cytoplasm and caspase-3 activation and further reduced apoptotic rates in H2O2-exposed IPEC-J2 cells. Mechanistically, depletion of sirtuin 1 (SIRT1) abrogated RSV's and PTS's benefits against mitochondrial reactive oxygen species overproduction, mitochondrial dysfunction, and apoptosis in H2O2-exposed IPEC-J2 cells, suggesting that SIRT1 was required for RSV and PTS to protect against oxidative stress-induced intestinal injury. In conclusion, RSV and PTS improve oxidative stress-induced intestinal injury by regulating mitochondrial redox homeostasis and function via SIRT1 signaling pathway. In offering this protection, PTS is superior to RSV.

Background Non-alcoholic fatty liver disease (NAFLD) is a frequently occurring clinical disease, which could be treated by traditional Chinese medicine. However, the effects and mechanisms of xiao-zhi-fang (XZF) alone or in combination with fructooligosaccharides (FOS) on NAFLD remains unclear. Methods This study established the NAFLD mouse model by feeding with a high-fat diet and by administering with XZF and/or FOS. Moreover, the fat content in the liver tissues was evaluated by oil red O and hematoxylin and eosin staining, and the liver function indices were examined using a biochemical analyzer. Changes in the intestinal flora were monitored using 16S rRNA gene sequencing. The results of the current study showed that the alanine aminotransferase, aspartate aminotransferase, total triglyceride, total cholesterol levels, and the amount of lipid accumulation were markedly elevated in NAFLD mice. Results XZF alone or in combination with FOS significantly reduced lipid accumulation in the liver and blood lipid levels in NAFLD mice. Moreover, XZF alone or in combination with FOS notably altered the intestinal flora structure in NAFLD mice. Consequently, 17 operational taxonomic units were decreased and nine were increased in the XZF and/or FOS groups. Conclusions FOS may accelerate the intestinal microecological balance in NAFLD mice after treatment with XZF by promoting intestinal flora growth, thereby enhancing the therapeutic effect of XZF on NAFLD.

The construction of intelligent near-infrared (NIR) fluorophores for high specificity to cancer cells and application in multiple therapeutic modalities is crucial for precise cancer diagnostic and therapy. In this study, an aggregation-induced emission-active NIR fluorophore (TACQ) with mitophagy-modulating activity was synthesized and developed for mitochondrial targeting multimodal cancer theranostics. The strengthened push-pull interaction extended the emission of TACQ into the NIR-II region (>1000 nm). Further, the rotor structure and twisted molecular conformation enables nanoaggregates of TACQ to balance the radiative and nonradiative decays to simultaneously exhibit bright NIR emission, high photothermal conversion efficiency (55%), and efficient generation of reactive oxygen species. The lipocationic property of TACQ allows it to selectively accumulate in the mitochondria of cancer cells. TACQ can induce mitophagy and block mitophagic flux facilitating cancer cell apoptosis. Both in vitro and in vivo evaluations revealed that TACQ is an efficient theranostic agent for NIR fluorescence and photothermal imaging-guided synergistic chemo-photothermal and photodynamic therapy.

The oxygen evolution reaction (OER) is critical for many clean energy conversion and storage technologies because it contributes the electrons required for converting renewable electricity into value-added chemicals. Electrocatalysts can promote the sluggish oxygen evolution process involving four-electron transfer. Herein, we prepare mesoporous spinel oxide nanosheets and develop an efficient strategy using Fe substitution to enable mesoporous NiCo2O4 nanosheets to generate superior active centers for the OER. Additionally, the iron substitution also promotes the preoxidation of Co/Ni and facilitates the formation of active species. Raman spectroscopy data reveal that the active species of mesoporous NiCo2O4 nanosheets for the OER is NiCo2O4 itself, and the active species of Fe substitution in NiCo2O4 nanosheets are Ni(Co) oxyhydroxides. Therefore, the iron substitution is beneficial to facilitate the transformation of spinel NiCo2O4 into active Ni(Co) oxyhydroxides under OER conditions. Owing to the mesoporous nanosheet structure and the formation of oxyhydroxide active species, the optimized mesoporous Fe0.2Ni0.8Co2O4 nanosheet catalyst exhibits a low overpotential of 270 mV to deliver a current density of 10 mA cm-2 and a small Tafel slope of 39 mV dec-1 for the oxygen evolution reaction in alkaline media.

Traditional dyeing process of cotton has caused a large amount of wastewater with high salt content, which seriously damages the ecological environment. In this work, cotton fabric was modified with 3-chloro-2-hydroxypropyl trimethyl ammonium chloride in order to decrease the electrostatic repulsion with the anionic dyes. A systematic optimization of the process has been performed. The acid dyes were applied instead of the common reactive dyes to dye the modified fabrics. The advantage of the high dye-uptake of acid dyes is studied. The levelness of the fabric dyed by reactive dyes and acid dyes were compared. The adsorption process and the bindings between the modified fabric and anionic acid dyes were further explored. The dyeing process were optimized. Finally, the dye-uptake of the modified fabric dyed by optimized conditions achieves to about 92%, which is comparable to traditional cotton dyeing process.

Understanding factors associated with disease severity and mortality from coronavirus disease (COVID-19) was critical for effective risk stratification. We aimed to investigate the association between biomarkers of clinical laboratory tests, including serum C-reactive protein (CRP), serum amyloid protein (SAA), lactate dehydrogenase (LDH), and D-dimer (DD) and poor prognosis of COVID-19. We have searched many studies on COVID-19 on PubMed (Medline), Web of Science and Cochrane until 1 March 2021. The interest of this study was original articles reporting on laboratory testing projects and outcome of patients with COVID-19 that comprises mortality, acute respiratory distress syndrome (ARDS), need for care in an intensive care unit (ICU), and severe COVID-19. After synthesizing all data, we performed meta-analysis of random effects, and determined mean difference (MD) and standard mean difference at the biomarker level for different disease severity. A total of 7,739 patients with COVID-19 were pooled from 32 studies. CRP was significantly associated with poor prognosis of COVID-19 (SMD = 0.98, 95% CI = (0.85, 1.11), p < .001). Elevated SAA was associated with an increased composite poor outcome in COVID-19 (SMD = 1.06, 95% CI = (0.39, 1.72), p = .002). An elevated LDH was associated with a composite poor outcome (SMD = 1.18, 95% CI = (1.00, 1.36), p < .001). Patients with a composite poor outcome had a higher DD level (SMD = 0.91, 95% CI = (0.79, 1.02), p < .001). This meta-analysis showed that elevated serum CRP, SAA, LDH, and DD were associated with a poor outcome in COVID-19.

Background Lignocellulosic biomass is an attractive and sustainable alternative to petroleum-based feedstock for the production of a range of biochemicals, and pretreatment is generally regarded as indispensable for its biorefinery. However, various inhibitors that severely hinder the growth and fermentation of microorganisms are inevitably produced during the pretreatment of lignocellulose. Presently, there are few reports on a single microorganism that can detoxify or tolerate toxic mixtures of pretreated lignocellulose hydrolysate while effectively transforming sugar components into valuable compounds. Alternatively, microbial coculture provides a simpler and more efficacious way to realize this goal by distributing metabolic functions among different specialized strains. Results In this study, a novel synthetic microbial consortium, which is composed of a responsible for detoxification bacterium engineered Pseudomonas putida KT2440 and a lactic acid production specialist Bacillus coagulans NL01, was developed to directly produce lactic acid from highly toxic lignocellulosic hydrolysate. The engineered P. putida with deletion of the sugar metabolism pathway was unable to consume the major fermentable sugars of lignocellulosic hydrolysate but exhibited great tolerance to 10 g/L sodium acetate, 5 g/L levulinic acid, 10 mM furfural and HMF as well as 2 g/L monophenol compound. In addition, the engineered strain rapidly removed diverse inhibitors of real hydrolysate. The degradation rate of organic acids (acetate, levulinic acid) and the conversion rate of furan aldehyde were both 100%, and the removal rate of most monoaromatic compounds remained at approximately 90%. With detoxification using engineered P. putida for 24 h, the 30% (v/v) hydrolysate was fermented to 35.8 g/L lactic acid by B. coagulans with a lactic acid yield of 0.8 g/g total sugars. Compared with that of the single culture of B. coagulans without lactic acid production, the fermentation performance of microbial coculture was significantly improved. Conclusions The microbial coculture system constructed in this study demonstrated the strong potential of the process for the biosynthesis of valuable products from lignocellulosic hydrolysates containing high concentrations of complex inhibitors by specifically recruiting consortia of robust microorganisms with desirable characteristics and also provided a feasible and attractive method for the bioconversion of lignocellulosic biomass to other value-added biochemicals.

Ampelopsin, a flavonoid with a wide variety of biological activities, has been proposed to be a potent antitumor agent. However, the mechanism by which Ampelopsin shows anti-breast cancer activity remains unclear. Therefore, this study will explore the mechanism of Ampelopsin's anti-breast cancer activity by culturing MDA-MB-231 and MCF-7 breast cancer cells. Cell Counting Kit-8 (CCK-8) method and plate cloning method were used to detect the proliferation inhibition of breast cancer cells. Fluorescence microscopy was used to detect mitochondrial membrane potential (MMP). 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) method was used to determine the content of intracellular reactive oxygen species (ROS). Hoechst 33258 staining was used to detect the apoptotic morphological changes. Transmission electron microscope was used to observe the mitochondrial structure. Western blot was used to detect the protein expression of Bax and Bcl-2. The results showed that Ampelopsin could significantly inhibit the proliferation of breast cancer cells, and promote cells apoptosis. In addition, the occurrence of apoptosis in breast cancer cells was associated with mitochondrial dysfunction, including the loss of mitochondrial membrane potential, the production of large amounts of reactive oxygen species, and the up-regulation of Bax/Bcl-2 expression. In conclusion, Ampelopsin-induced mitochondria damage leads to loss of mitochondria membrane potential, overproduction of ROS and activation of Bax, increasing mitochondria membrane permeability and ultimately inducing breast cell apoptosis. These findings provided a new perspective on the role of Ampelopsin in breast cancer prevention and treatment.

Achieving the transition metal-catalysed pyridine C3-H alkenylation, with pyridine as the limiting reagent, has remained a long-standing challenge. Previously, we disclosed that the use of strong coordinating bidentate ligands can overcome catalyst deactivation and provide Pd-catalysed C3 alkenylation of pyridines. However, this strategy proved ineffective when using pyridine as the limiting reagent, as it required large excesses and high concentrations to achieve reasonable yields, which rendered it inapplicable to complex pyridines prevalent in bioactive molecules. Here we report that a bifunctional N-heterocyclic carbene-ligated Ni-Al catalyst can smoothly furnish C3-H alkenylation of pyridines. This method overrides the intrinsic C2 and/or C4 selectivity, and provides a series of C3-alkenylated pyridines in 43-99% yields and up to 98:2 C3 selectivity. This method not only allows a variety of pyridine and heteroarene substrates to be used as the limiting reagent, but is also effective for the late-stage C3 alkenylation of diverse complex pyridine motifs in bioactive molecules.

Mei-Qi Xu,1,2 Yan-Li Hao,1,2 Jing-Ru Wang,1,2 Zhuo-Yue Li,1,2 Hui Li,1 Zhen-Han Feng,1,2 Hui Wang,1,2 Jing-Wen Wang,1,2 Xuan Zhang1,2 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People’s Republic of ChinaCorrespondence: Xuan ZhangDepartment of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, Beijing, 100191, People’s Republic of ChinaTel +86-10-82805765Fax +86-10-8280576Email xuanzhang@bjmu.edu.cnPurpose: Small molecule modified antitumor drug conjugate nanoparticles have the advantages of high drug loading, simple synthesis and preparation, and better biocompatibility. Due to the large demand for exogenous α-linolenic acid (ALA) by tumor cells, we synthesized α-linolenic acid-paclitaxel conjugate (ALA-PTX) and prepared α-linolenic acid-paclitaxel conjugate nanoparticles (ALA-PTX NPs), in order to obtain better tumor cellular uptake and antitumor activity in vitro and in vivo.Methods: We synthesized and characterized ALA-PTX, and then prepared and characterized ALA-PTX NPs. The cellular uptake, uptake pathways, intracellular behavior, in vitro and in vivo antitumor activity of ALA-PTX NPs were evaluated.Results: The size of ALA-PTX NPs was approximately 110.7± 1.7 nm. The drug loading was approximately 90% (w/w) with CrEL-free and organic solvent-free characteristics. The cellular uptake of ALA-PTX NPs was significantly higher than that of PTX injection by MCF-7, MCF-7/ADR and HepG2 cells. In these three cell lines, the cellular uptake of ALA-PTX NPs at 6h was approximately 1.5– 2.6 times higher than that of PTX injection. ALA-PTX NPs were ingested through clathrin-mediated endocytosis, then transferred to lysosomes, and could dissolve in cells to play an antitumor activity. The in vitro and in vivo antitumor activity of ALA-PTX NPs was confirmed in MCF-7/ADR and HepG2 cell models and tumor-bearing nude mouse models.Conclusion: ALA-PTX NPs developed in our study could provide a new method for the preparation of nano-delivery systems suitable for antitumor therapy that could increase tumor cellular uptake and enhance antitumor activity.Keywords: α-linolenic acid, α-linolenic acid-paclitaxel conjugate, α-linolenic acid-paclitaxel conjugate nanoparticles, cellular uptake, antitumor activity

The complement system plays a key role in opsonization and immune clearance of engineered nanoparticles. Understanding the efficiency, inter-subject, and inter-strain differences of complement opsonization in preclinical species can help with translational nanomedicine development and improve our ability to model complement response in humans. Dextran-coated superparamagnetic iron oxide (SPIO) nanoparticles and a wide range of non-magnetic iron oxide nanoparticle formulations are widely used in magnetic resonance imaging and as clinically approved iron supplements. Previously we found that opsonization of SPIO nanoworms (NW) with the third complement protein (C3) proceeds mostly via the alternative pathway in humans, and via the lectin pathway in mice. Here, we studied the pathway and efficiency of opsonization of 106 nm SPIO NW with C3 in different preclinical species and commonly used laboratory strains. In sera of healthy human donors (n = 6), C3 opsonization proceeded exclusively through the alternative pathway. On the other hand, the C3 opsonization in dogs (6 breeds), rats (4 strains) and mice (5 strains) sera was either partially or completely dependent on the complement Ca2+-sensitive pathways (lectin and/or classical). Specifically, C3 opsonization in sera of Long Evans rat strain, and mouse strains widely used in nanomedicine research (BALB/c, C57BL/6 J, and A/J) was only through the Ca2+-dependent pathways. Dogs and humans had the highest between-subject variability in C3 opsonization levels, while rat and mouse sera showed the lowest between-strain variability. Furthermore, using a panel of SPIO nanoparticles of different sizes and dextran coatings, we found that the level of C3 opsonization (C3 molecules per milligram Fe) in human sera was lower than in animal sera. At the same time, there was a strong predictive value of complement opsonization in dog and rat sera; nanoparticles with higher C3 deposition in animals showed higher deposition in humans, and vice versa. Notably, the opsonization decreased with decreasing size in all sera. The studies highlight the importance of the consideration of species and strains for predicting human complement responses (opsonization) towards nanomedicines.

Background. Hypertrophic scar (HS) is a benign fibroproliferative skin disease resulting from an aberrant wound healing process and can cause aesthetic and functional damage to patients. Currently, there is no ideal treatment to treat this disease. Galangin, a natural active bioflavonoid compound, is suggested to inhibit fibrosis and proliferation in certain cells. Methods. In this study, we found Galangin could attenuate abnormal scar formation in an HS rabbit ear model. Additionally, the HE staining shows Galangin reduced scar elevation index (SEI) and Masson’s trichrome staining changed collagen deposition. Results. The expressions of type I collagen, type III collagen, and TGF-β1 were much lower under a proper dose of Galangin treatment, and Smad7 expression was also enhanced, which are examined by real-time PCR, immunohistochemistry, and western blot. Conclusion. Our data indicated that Galangin can alleviate dermal scarring via the TGF-β/Smad signaling pathway probably by upregulating Smad 7 expression and, thus, suppressing the expression of type I and type III collagens and TGF-β1.

Selective photocatalysis is a very promising direction to improve the activities of photocatalysts. Combining the technique of molecular imprinting (MIP) with heterogeneous photocatalysis can be an appealing approach to achieve our aim. Herein, using the MIP technique, the monoclinic MIP-BiVO4 was successfully synthesized by the presence of rhodamine B (RhB) during the hydrothermal synthesis. The synthesized MIP-BiVO4 possessed better adsorptive and photocatalytic activities than pristine BiVO4. RhB added in the synthesis process worked as a template and served a crucial role in the formation of the MIP-BiVO4 morphology. The photoelectrochemical analysis verified the superiority of MIP-BiVO4 sample in the transfer and separation of the electron–hole pairs. Holes played the most crucial role in the degradation of the pollutants. The effective approach combining MIP technique in the synthesis of photocatalysts would provide some guidance to selective photocatalysis field for designing and synthesizing highly efficient photocatalysts.

γ-Aminobutyric acid (GABA), a signal molecule, is regarded as the intersection node of carbon and nitrogen metabolism, and its contributions to flavonoid metabolism in tea plant growth and development remain unclear. The correlation between the GABA shunt and flavonoid metabolism in tea plants is worth to explore. Secondary metabolites and their correlations with the taste of tea soup made from tea plants (Camellia sinensis) during different seasons were investigated. Related secondary metabolites and transcript profiles of genes encoding enzymes in the GABA shunt, flavonoid pathway and polyamine biosynthesis were measured throughout the tea plant growth seasons and after exogenous GABA applications. In addition, the abundance of differentially expressed proteins was quantified after treatments with or without exogenous GABA. The tea leaves showed the highest metabolite concentrations in spring season. CsGAD, CsGABAT, CsSPMS, CsODC, CsF3H and CsCHS were found to be important genes in the GABA and anthocyanin biosynthesis pathways. GABA and anthocyanin concentrations showed a positive correlation, to some extent, CsF3H and CsCHS played important roles in the GABA and anthocyanin biosynthesis.

A novel method for the synthesis of 3-monohalooxindoles by acidolysis of isatin-derived 3-phosphate-substituted oxindoles with haloid acids was developed. This synthetic strategy involved the preparation of 3-phosphate-substituted oxindole intermediates and SN1 reactions with haloid acids. This new procedure features mild reaction conditions, simple operation, good yield, readily available and inexpensive starting materials, and gram-scalability.

Objectives The second-generation integrase strand transfer inhibitor (INSTI) bictegravir is becoming accessible in low- and middle-income countries (LMICs), and another INSTI, cabotegravir, has recently been approved as a long-acting injectable. Data on bictegravir and cabotegravir susceptibility in raltegravir-experienced HIV-1 subtype A- and D-infected patients carrying drug resistance mutations (DRMs) remain very scarce in LMICs. Patients and methods HIV-1 integrase (IN)-recombinant viruses from eight patients failing raltegravir-based third-line therapy in Uganda were genotypically and phenotypically tested for susceptibility to bictegravir and cabotegravir. Ability of these viruses to integrate into human genomes was assessed in MT-4 cells. Results HIV-1 IN-recombinant viruses harbouring single primary mutations (N155H or Y143R/S) or in combination with secondary INSTI mutations (T97A, M50I, L74IM, E157Q, G163R or V151I) were susceptible to both bictegravir and cabotegravir. However, combinations of primary INSTI-resistance mutations such as E138A/G140A/G163R/Q148R or E138K/G140A/S147G/Q148K led to decreased susceptibility to both cabotegravir (fold change in EC50 values from 429 to 1000×) and bictegravir (60 to 100×), exhibiting a high degree of cross-resistance. However, these same IN-recombinant viruses showed impaired integration capacity (14% to 48%) relative to the WT HIV-1 NL4-3 strain in the absence of drug. Conclusions Though not currently widely accessible in most LMICs, bictegravir and cabotegravir offer a valid alternative to HIV-infected individuals harbouring subtype A and D HIV-1 variants with reduced susceptibility to first-generation INSTIs but previous exposure to raltegravir may reduce efficacy, more so with cabotegravir.

A mixture of sucrose (Suc) and citric acid (Cit) was added as a pretreatment agent to regulate the crispy texture of explosion-puffing-dried (EPD) yellow peach slices and ensure color and sensory p...

Intracerebral haemorrhage (ICH) can be a catastrophic event; even if the initial stages of the pathology were well-managed, a number of patients experience varied residual neurological deficits following the insult. Ferroptosis is a recently identified type of cell demise which is tightly linked to the neurological impairment associated with ICH. In the current work, the prophylactic impact of scalp acupuncture (SA) therapy on autologous blood injection murine models of ICH was investigated in order to establish whether SA could mitigate the secondary damage arising following ICH by moderating ferroptosis. The pathophysiological mechanisms associated with this process were also explored. Ludmila Belayev tests were utilised for the characterisation of neurological damage. Haematoxylin–eosin staining was employed in order to determine the cerebral impact of the induced ICH. Malondialdehyde (MDA) and iron titres in peri-haemorrhagic cerebral tissues were appraised using purchased assay kits. Transmission electron microscopy delineated mitochondrial appearances within nerve cell bodies from the area of haemorrhage. Western blotting techniques were utilised to assay the degree of protein expression of NeuN, sequestosome 1 (p62), nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1). The frequencies of Nrf2, GPX4 and FTH1 positive cells, respectively, were documented with immunohistochemical staining. The results demonstrated that therapy with SA after ICH mitigated MDA and iron sequestration, diminished the appearance of contracted mitochondria with increased outer mitochondrial membrane diameter within the nerve cell bodies, and suppressed neuronal ferroptosis. The pathways responsible for these effects may encompass amplified p62, Nrf2, GPX4 and FTH1 expression, together with decreased Keap1 expression. Application of SA reduced identified neurobehavioural abnormalities after ICH; no disparities were observed between the consequences of SA therapy and deferoxamine delivery. It can be surmised that intervention with SA enhanced recovery after ICH by triggering the antioxidant pathway, p62/Keap1/Nrf2, and causing FTH1 and GPX4 upregulation, factors that participate in diminishing excess iron and thus in mitigating lipid peroxidation insults arising from ferroptosis following ICH. Supplementary Information The online version contains supplementary material available at 10.1007/s12031-021-01890-y.

There are many defects in the post finishing flame-retardant modification of polyester–cotton (CT) fabric, leading to shortcomings such as single function and low flame-retardant efficiency, which still need to be solved urgently. Herein, a bio-based flame-retardant and antibacterial coating consisting of phytic acid and DL-arginine was deposited on CT fabrics using layer-by-layer assembly to obtain a flame-retardant and antibacterial CT fabric. Fourier transform infrared spectroscopy confirmed that the assembled coating was successful deposited on the CT fabric. The thermogravimetric analysis revealed that the number of bilayers had no significant effect on the degradation temperature of the coated CT fabric; however, it significantly improved the charring effect of the sample, wherein the char rate of the CT fabric coated with 20 bilayers increased from 0.11 to 8.67 wt% compared with uncoated CT fabric at 700°C. In addition, the limiting oxygen index of the CT fabric coated with 20 bilayers increased to 32.0 ± 0.3%. Furthermore, the vertical results revealed that the CT fabric coated with five bilayers attained the UL-94 V-1 grade. The heat release rate (HRR) and the total heat release (THR) of the coated CT fabric were significantly decreased compared to those of the uncoated CT fabric. In particular, the HRR and THR of the CT fabric coated with five bilayers reduced by 28.97% and 30.49%, respectively. Furthermore, the coated CT fabric exhibited an obvious antibacterial effect on Staphylococcus aureus, and the inhibitory ring increased from 0 to 4.0 mm with an increase in bilayers to 20. This study describes a facile method of flame-retardant and antibacterial modification of CT fabric using biological materials.

Background Immune thrombocytopenia (ITP) is an autoimmune disease characterized as a low platelet count resulting from immune-mediated platelet destruction. Dimethyl fumarate (DMF) is widely applied for the treatment of several autoimmune diseases with immunosuppressive effect. However, whether it ameliorates ITP is unclear. This study aims to evaluate whether DMF has a preventive effect on ITP in mice. Methods DMF (30, 60 or 90 mg/kg body weight) was intraperitoneally injected into mice followed by injection of rat anti-mouse integrin GPIIb/CD41antibody to induce ITP. Peripheral blood was isolated to measure platelet count and spleen mononuclear cells were extracted to measure Th1 and Treg cells along with detecting the levels of IFN-γ, and TGFβ-1 in plasma and CD68 expression in spleen by immuohistochemical staining. Additionally, macrophage cell line RAW264.7 was cultured and treated with DMF followed by analysis of cell apoptosis and cycle, and the expression of FcγRI, FcγRIIb and FcγRIV mRNA. Results DMF significantly inhibited antiplatelet antibody-induced platelet destruction, decreased Th1 cells and the expression of T-bet and IFN-γ, upregulated Treg cells and the expression of Foxp3 and TGF-β1 as well as reduced CD68 expression in the spleen of ITP mouse. DMF-treated RAW264.7 cells showed S-phase arrest, increased apoptosis and downregulated expression of FcγRI and FcγRIV. Meanwhile, in vitro treatment of DMF also decreased the expression of cyclin D1 and E2, reduced Bcl-2 level and increased Bax expression and caspase-3 activation. Conclusions In conclusion, DMF prevents antibody-mediated platelet destruction in ITP mice possibly through promoting apoptosis, indicating that it might be used as a new approach for the treatment of ITP.

A self-supporting catalyst consisting of 1D/2D vertical molybdenum disulfide@titanium dioxide/nitrogen-doped carbon nanofiber (MoS2@TiO2/NCNFs) was prepared and tested. It showed efficient hydrogen peroxide (H2O2) decomposition to generate hydroxyl radical ( OH) and degradation of various pollutants under solar irradiation. The contribution of the increase in MoS2 edges for decomposing H2O2 was 0.0698 min−1. That is 9.83 times the rate of the original MoS2 edges resulting from the vertical structure. Specially, the catalyst degraded various aromatic pollutants even in the dark by releasing electrons stored in its graphite component to realize “memory catalysis”. Also, it exhibited high degradation efficiency under outdoor solar irradiation. The catalyst was easily separated from the treated water, avoiding complex separation processes. All these features suggest this catalyst has great potential in practical water and sewage treatment applications.

Cell-cell communication is critical for bacterial survival in natural habitats, in which miscellaneous regulatory networks are encompassed. However, elucidating the interaction networks of a microbial community has been hindered by the population complexity. This study reveals that γ-butyrolactone (GBL) molecules from Streptomyces species, the major antibiotic producers, can directly bind to the acyl-homoserine lactone (AHL) receptor of Chromobacterium violaceum and influence violacein production controlled by the quorum sensing (QS) system. Subsequently, the widespread responses of more Gram-negative bacterial AHL receptors to Gram-positive Streptomyces signaling molecules are unveiled. Based on the cross-talk between GBL and AHL signaling systems, combinatorial regulatory circuits (CRC) are designed and proved to be workable in Escherichia coli (E. coli). It is significant that the QS systems of Gram-positive and Gram-negative bacteria can be bridged via native Streptomyces signaling molecules. These findings pave a new path for unlocking the comprehensive cell-cell communications in microbial communities and facilitate the exploitation of innovative regulatory elements for synthetic biology.

A copper-catalyzed four-component chloro-arylsulfonylation of styrene derivatives with aryldiazonium tetrafluoroborates, lithium chloride, and ex-situ generated sulfur dioxide (from SOgen) is presented. This sulfonylation features good functional group compatibility, mild reaction conditions, excellent regioselectivity, and good yields. The robustness and potential of this method have also been successfully demonstrated by a gram-scale reaction. Based on experimental study, a radical-involved mechanism is proposed for the transformation.

Background In recent years, protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitors have been widely studied as important agricultural herbicides. Our research effort was focused on the design and synthesis of novel PPO inhibitor herbicides, done through the linking of a diphenylether pyridine bioisostere structure to substituted coumarins, which aims to enhance environmental and crop safety while retaining high efficacy. The work done in our research are the design and synthesize of a series of phenoxypyridine derivatives. Results In this work, a total of 21 compounds were synthesized via acylation reactions and all the compounds were characterized using IR, 1 H-NMR, 13 C-NMR, and high-resolution mass spectra. The respective configuration of compound IV-6 and IV-12 were also confirmed using single crystal X-ray diffraction. The bioassay results showed that the title compounds displayed notable herbicidal activity, especially compound IV-6 which displayed better herbicidal activity in greenhouse and field experiments, crop selectivity and safety for cotton and soybean as compared to that of the commercial herbicide oxyfluorfen. Conclusion The present work revealed that the compound IV-6 deserves further attention as the candidate structure of novel and safe herbicide. This article is protected by copyright. All rights reserved.

Elevated circulating trimethylamine N-oxide (TMAO) concentrations have been observed in patients with chronic kidney disease (CKD). We aimed to systematically estimate and quantify the association between TMAO concentrations and kidney function. The PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science databases were systematically searched from 1995 to 1 June, 2020, for clinical studies on circulating TMAO concentrations and kidney function indicators. We used R software to conduct meta-analyses of the extracted data. A cumulative meta-analysis was applied to test whether health status affected the pooled effect value. Meta-regression and subgroup analyses were performed to identify possible sources of heterogeneity. Ultimately, we included a total of 32 eligible clinical studies involving 42,062 participants. In meta-analyses of continuous-outcome variables, advanced CKD was associated with a 67.9 μmol/L (95% CI: 52.7, 83.2; P < 0.01) increase in TMAO concentration, and subjects with high concentrations of TMAO had a 12.9 mL/(min·1.73 m(2)) (95% CI: −16.6, −9.14; P < 0.01) decrease in glomerular filtration rate (GFR). In meta-analyses of the correlations, TMAO was strongly inversely correlated with GFR [Fisher's z-transformed correlation coefficient (ZCOR): −0.45; 95% CI: −0.58, −0.32; P < 0.01] and positively associated with the urine albumin-to-creatinine ratio (UACR; ZCOR: 0.26; 95% CI: 0.08, 0.43; P < 0.01), serum creatinine (sCr; ZCOR: 0.43; 95% CI: 0.28, 0.58; P < 0.01), urine albumin excretion rate (UAER; ZCOR: 0.06; 95% CI: 0.04, 0.09; P < 0.01), blood urea (ZCOR: 0.50; 95% CI: 0.29, 0.72; P < 0.01), blood uric acid (ZCOR: 0.32; 95% CI: 0.25, 0.38; P < 0.01), and serum cystatin C (CysC; ZCOR: 0.47, 95% CI: 0.44, 0.51; P < 0.01). This is the first systematic review and meta-analysis to reveal a negative association between circulating TMAO concentrations and kidney function.

Acute stress relates to high prevalence of anxiety, depression or even sudden death. Although dopaminergic system in amygdala-medial prefrontal cortex (mPFC) circuit is hyper-responsive to stress-induced anxiety, the mechanisms that control anxiety still remains unanswered. Here, the acute restraint stress model(ARS) was established to develop anxiety-like behavior. The D2-dopamine receptor (D2R) availability in amygdala and mPFC was assessed using [18F]-fallypride positron emission tomography(PET) and immunohistochemical assay. We revealed that ARS paradigm was successfully established, as evidenced by elevated plus-maze test(EPM) and increased corticosterone release. Moreover, PET imaging displayed elevated D2R availability in the amygdala and mPFC in ARS as compared to that in the naives. PET imaging combined with immunohistochemical assay confirmed that amygdaloid D2R was significantly implicated in stress-induced anxiety. Our findings delivered valuable insights into neuromechanism of amygdaloid D2R underlying stress-induced anxiety and might have important implications for developing therapeutics for anxiety by targeting amygdaloid D2R.

The small organic molecule electro-oxidation (OMEO) and the hydrogen evolution (HER) are two important half-reactions in direct liquid fuel cells (DLFCs) and water electrolyzers, respectively, whose performance is largely hindered by the low activity and poor stability of electrocatalysts. Herein, we demonstrate that a simple phosphorization treatment of commercially available palladium-nickel (PdNi) catalysts results in multifunctional ternary palladium nickel phosphide (PdNiP) catalysts, which exhibit substantially enhanced electrocatalytic activity and stability for HER and OMEO of a number of molecules including formic acid, methanol, ethanol, and ethylene glycol, in acidic and/or alkaline media. The improved performance results from the modification of electronic structure of palladium and nickel by the introduced phosphorus and the enhanced corrosion resistance of PdNiP. The simple phosphorization approach reported here allows for mass production of highly-active OMEO and HER electrocatalysts, holding substantial promise for their large-scale application in direct liquid fuel cells and water electrolyzers.

BACKGROUND: Some scholars have found that dermal papilla spheroid–derived exosomes could promote the development of hair follicles. However, whether adipose-derived stem cell exosomes (ADSC-Exos) have a similar effect on hair growth has not been determined yet. Thus, the purpose of this article was to detect whether ADSC-Exos could promote hair regeneration. METHODS: Adipose-derived stem cells (ADSCs) were isolated from 6-week-old C57BL/6 mice. Then, ADSC-Exos were isolated from the ADSCs. Western blotting was used to detect specific exosome markers. The particle size and distribution of the exosomes were analyzed by NanoSight dynamic light scattering. A total of 12 nude mice were randomly divided into two groups (n = 6 each): the ADSC-Exos group and the control group. For the control group, a mixture of freshly isolated dermal cells (DCs) and epidermal cells (ECs) was grafted. For the ADSC-Exos group, a mixture of DCs, ECs, and 50 μg/ml of ADSC-Exos was grafted. Gross evaluation of the hair regeneration was carried out 2–3 weeks after the transplantation, and the graft site was harvested for histology at the third week. RESULTS: The existence of exosomes derived from ADSCs was evidenced by CD63, ALX1, and CD9 expression. Two or three weeks after the grafting, the number of regenerated hairs in the ADSC-Exos group was higher than that in the control group (p

It was observed in this work that application of Pb and B[a]P co-exposure significantly (p

The deactivation issue arising from alkali poisoning over catalysts is still a challenge for the selective catalytic reduction of NOx by NH3. Herein, improved NOx reduction in the presence of alkaline metals over phosphate-modified Fe2O3/TiO2 catalysts has been originally demonstrated via tailoring the reaction paths by in situ creating alkali-poisoning sites. The introduction of phosphate results in the partial formation of iron phosphate species and makes the catalyst to mainly exhibit the characteristics of FePO4, which is responsible for the widened temperature window and enhanced alkali resistance. The tetrahedral [FeO4]/[PO4] structures in iron phosphate act as the Bronsted acid sites to increase the catalyst surface acidity. In addition, the formation of an Fe-O-P structure enhances the redox ability and increases surface adsorbed oxygen. Furthermore, the created phosphate groups (PO43-) serving as alkali-poisoning sites preferentially combine with potassium so that iron species on the active sites are protected. Therefore, the enhanced NH3 species adsorption capacity, improved redox ability, and active nitrate species remaining in the phosphate-modified Fe2O3/TiO2 catalyst ensure the de-NOx activity after being poisoned by alkali metals through the Langmuir-Hinshelwood reaction pathway. Hopefully, this novel strategy could provide an inspiration to design novel catalysts to control NOx emission with extraordinary resistance to alkaline metals.

The programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway is abnormally expressed in cervical cancer cells. Moreover, PD-1/PD-L1 blockade reduces the apoptosis and exhaustion of T cells and inhibits the development of malignant tumors. Usnic acid is a dibenzofuran compound originating from Usnea diffracta Vain and has anti-inflammatory, antifungal, and anticancer activities. However, the molecular mechanism of its antitumor effects has not been fully elucidated. In this work, we first observed that usnic acid decreased the expression of PD-L1 in HeLa cells and enhanced the cytotoxicity of co-cultured T cells toward tumor cells. Usnic acid inhibited PD-L1 protein synthesis by reducing STAT3 and RAS pathways cooperatively. It was subsequently shown that usnic acid induced MiT/TFE nuclear translocation through the suppression of mTOR signaling pathways, and promoted the biogenesis of lysosomes and the translocation of PD-L1 to the lysosomes for proteolysis. Furthermore, usnic acid inhibited cell proliferation, angiogenesis, migration, and invasion, respectively, by downregulating PD-L1, thereby inhibiting tumor growth. Taken together, our results show that usnic acid is an effective inhibitor of PD-L1 and our study provide novel insights into the mechanism of its anticancer targeted therapy.

To explore whether acupuncture can improve sleep disturbance, cognitive impairment and emotional disorders caused by sleep deprivation, and its association with the attenuation of oxidative stress injury in prefrontal cortex. Fifty-two male Sprague-Dawley rats were randomly divided into a control group (n=10), a model group (n=14), a manual acupuncture (MA) group (n=14), and a sham-MA group (n=14). All the groups were established as sleep deprivation models via the modified multiple platform method, except for the control group. Rats in both the MA group and the sham-MA group received corresponding intervention, respectively. After modeling and intervention, the four groups received three behavioral tests, namely sleep monitoring, by comprehensive lab animal monitoring system (CLAMS), Morris water maze (MWM) test and open-field test (OFT), followed by oxygen free radical level test and Western blot (WB) detection for the expression levels of Bax and Bcl-2. The MA group derived more sleep time within 24 h than either the model group or the sham-MA group (both P 0.05), and the escape latency was significantly shorter in these three groups than that in the model group (all P

A comprehensive study on the accretion and diagenesis of the Permian–Triassic boundary microbialites is conducive to a better understanding of the ecological community after the end-Permian mass extinction. Here we studied the special microbialite sequences at the Tianba section of Leye isolated carbonate platform, South China Block. The microbialites are shown as small columnar stromatolites, stromatolitic thrombolites, spotted thrombolites, and domical digitate thrombolites in an ascending order. Thin section analyses, coupled with cathodoluminescence photos and oxygen isotopic data, reveal that all types of microbially-mediated laminae/clots are partly recrystallized. Layers of the Polybessurus-like fossils commonly occur in the recrystallized fabrics of stromatolitic laminae. However, the Polybessurus-like fossils are rare in quantity and generally fragmentary and structureless in stromatolitic clots and spotted clots. Such taphonomic features are likely interpreted as the early decomposition by heterotrophic bacteria in an oxygen-depleted microenvironment caused by rapid accumulations of organic matter in the calm water. More enrichments of 13C in the laminae of stromatolite and in the clots of stromatolitic thrombolite and spotted thrombolite than in adjacent interstitial matrixes signify the photosynthesis-dominated isotopic fractionation during the growth of microbial communities. Rare calcimicrobial structures but many calcite crystal fans were found in the 13C-depleted digitate clots. These phenomena indicate that seawater on the carbonate platform was 12C-enriched and supersaturated, accelerating carbonate precipitations and decompositions of organic matter within the microbial community. Different preservations of the Polybessurus-like fossil revealed the complicated microbially-dominated sedimentation and post-depositional diagenesis in the abnormal seawater after the catastrophe.

Lipopolysaccharide (LPS) is an important pathogenic factor for sepsis which results in cardiovascular diseases and even mortality. Proanthocyanidin, one of the main components in grape seed, has a wide range of biological activities in various diseases. The mouse model was established by intraperitoneal injection with LPS. Grape seed proanthocyanidin (GSP) was administered continuously for 8 days. Our results showed that pre-treatment of GSP dramatically ameliorated the level of creatine kinase (CK) and lactate dehydrogenase (LDH) to defend against LPS-induced myocardial toxicity (p

Design and development of intelligent fire warning materials with rapid response capabilities has always been an urgent need for the safety of many flammable materials in their applications. Herein...

Space cooling and heating consume a large proportion of global energy, so passive thermal management materials (i.e., without energy input), especially dual-mode materials including cooling and heating bifunctions, are becoming more and more attractive in many areas. Herein, a function-switchable Janus membrane between cooling and heating consisting of a multilayer structure of polyvinylidene fluoride nanofiber/zinc oxide nanosheet/carbon nanotube/Ag nanowire/polydimethylsiloxane was fabricated for comprehensive thermal management applications. In the cooling mode, the high thermal radiation emissivity (89.2%) and sunlight reflectivity (90.6%) of the Janus membrane resulted in huge temperature drops of 8.2-12.6, 9.0-14.0, and 10.9 °C for a substrate, a closed space, and a semiclosed space, respectively. When switching to the heating mode, temperature rises of 3.8-4.6, 4.0-4.8, and 12.5 °C for the substrate, closed space, and semiclosed space, respectively, were achieved owing to the high thermal radiation reflectivity (89.5%) and sunlight absorptivity (74.1%) of the membrane. Besides, the Janus membrane has outstanding comprehensive properties of the membrane, including infrared camouflaging/disguising, electromagnetic shielding (53.1 dB), solvent tolerance, waterproof properties, and high flexibility, which endow the membrane with promising application prospects.

Epigallocatechin gallate (EGCG), the main polyphenolic substance in tea, exhibits well-known biological benefits. In order to improve fat solubility and bioavailability, a novel path for the lipase enzymatic transesterification synthesis of acylated EGCG derivatives in an ionic liquid solvent was established. The optimal reaction parameters were determined and a maximum conversion of the transesterification reaction was achieved at 98.65%. [Bmim][BF4] was the best reaction medium and the immobilized lipase Novozym 435 was the best catalyst. The enzyme was added to a final concentration of 2% (w/w, EGCG), and the reaction was performed at an optimum temperature of 70°C stirring for 10 h at 250 rpm. The most suitable acyl donor, vinyl acetate, and EGCG were mixed at a molar ratio of 90:1 for the reaction. The structure of the purified acetylated EGCG was determined to be 5″-O-acetyl-EGCG and 3″, 5″-2-O-acetyl-EGCG by mass spectrometry, NMR, and infrared analyses.

Background This study aimed to investigate the expression characteristics of ANGPTL8 in patients with primary nephrotic syndrome and its possible correlation with hyperlipidemia and proteinuria. Methods ANGPTL8 levels were determined using an enzyme-linked immunosorbent assay in 133 subjects with PNS and 60 healthy controls. Results Compared with healthy controls, subjects with primary nephrotic syndrome had higher levels of serum and urine ANGPTL8 (P P P P P P P = 0.002). Interestingly, the urine ANGPTL8 concentrations in membranous nephropathy and mesangial proliferative glomerulonephritis pathological types were different. Conclusions Serum and urine ANGPTL8 levels in primary nephrotic syndrome patients were correlated with blood lipid levels and proteinuria, respectively, suggesting that ANGPTL8 may play a role in the development of primary nephrotic syndrome hyperlipidemia and proteinuria.

Conventional C–H alkenylation with alkynes via low-valent transition-metal catalysis occurs at the C6 or C4 position of 2-pyridone with electron-deficient C–H bonds. A bifunctional ligand-bonded Ni...

Cancer immunotherapy is a strategy that is moving to the frontier of cancer treatment in the current decade. In this study, we show evidence that 3-(2-nitrophenyl) propionic acid-paclitaxel nanoparticles (NPPA-PTX NPs), act as immunogenic cell death (ICD) inducers, stimulating an antitumor response which results in synergistic antitumor activity by combining anti-PD-L1 antibody (aPD-L1) in vivo. To investigate the antitumor immunity induced by NPPA-PTX NPs, the expression of both ICD marker calreticulin (CRT) and high mobility group box 1 (HMGB1) were analyzed. In addition, the antitumor activity of NPPA-PTX NPs combined with aPD-L1 in vivo was also investigated. The immune response was also measured through quantitation of the infiltration of T cells and the secretion of pro-inflammatory cytokines. The results demonstrate that NPPA-PTX NPs induce ICD of MDA-MB-231 and 4T1 cells through upregulation of CRT and HMGB1, reactivating the antitumor immunity via recruitment of infiltrating CD3+, CD4+, CD8+ T cells, secreting IFN-γ, TNF-α, and the enhanced antitumor activity by combining with aPD-L1. These data suggest that the combined therapy has a synergistic antitumor activity and has the potential to be developed into a novel therapeutic regimen for cancer patients.