Tobacco as a promising crop for low-carbon biorefinery.

Energy crops play a vital role in meeting future energy and chemical demands while addressing climate change. However, the idealization of low-carbon workflows and careful consideration of cost-benefit equations are crucial for their more sustainable implementation. Here, we propose tobacco as a promising energy crop because of its exceptional water solubility, mainly attributed to a high proportion of water-soluble carbohydrates and nitrogen, less lignocellulose, and the presence of acids. We then designed a strategy that maximizes biomass conversion into bio-based products while minimizing energy and material inputs. By autoclaving tobacco leaves in water, we obtained a nutrient-rich medium capable of supporting the growth of microorganisms and the production of bioproducts without the need for extensive pretreatment, hydrolysis, or additional supplements. Additionally, cultivating tobacco on barren lands can generate sufficient biomass to produce approximately 573 billion gallons of ethanol per year. This approach also leads to a reduction of greenhouse gas emissions by approximately 76% compared to traditional corn stover during biorefinery processes. Therefore, our study presents a novel and direct strategy that could significantly contribute to the goal of reducing carbon emissions and global sustainable development compared to traditional methods.

Bank erosion under the impacts of fluvial erosion, frost heaving/freeze-thaw process of rivers in seasonal frozen regions.

Bank erosion is a key feature of channel evolution in alluvial rivers, and will occur under the combined effect of hydraulic erosion and frost heave/freeze-thaw process of rivers in seasonal frozen regions. However, most research on bank erosion modeling has seldom considered the impact of the frost heave/freeze-thaw process. Therefore, the variation in the mechanical characteristics of riverbank soil under the freeze-thaw cycle was investigated firstly in the current research and then used in the modeling of bank erosion processes at typical sections of the Songhua River. Additionally, a sensitivity analysis of riverbank stability was conducted using orthogonal experiments. The results indicate that after 7 freeze-thaw cycles, the soil cohesion and internal friction angle of bank soil decreased by about 10%-47 % and 9%-19 %, respectively. Unlike lowland rivers, bank erosion of rivers in seasonal frozen regions is more likely to occur during the rising water period. The frost heaving/freeze-thaw process will make the bank stability safety coefficient Fs more quickly decrease to the unstable critical value. As compared with the case without considering the frost heaving/freeze-thaw process, the mass failure occurred in advance when the frost heaving/freeze-thaw process was considered, and the calculated bank erosion volume was increased by 11%-51 %, agreeing better with the measured value. The sensitivity ranking of the four influencing factors on riverbank stability under freezing-thawing conditions is as follows: river stage > groundwater level > cohesion > internal friction angle. The current study can provide a reference for research on bank erosion and channel evolution of rivers in seasonal frozen regions.

Seasonal and interannual variations of nutrients in the Subei Shoal and their implication for the world's largest green tide.

The world's largest "green tide" (Ulva prolifera) has occurred every year since 2007 in the Yellow Sea. The Subei Shoal area is thought to be the origin of the green tide. Based on field data from 2016 to 2023, seasonal and interannual variations of dissolved nutrients and their ecological effects in the Subei Shoal were analyzed. Spatial distribution of dissolved inorganic nitrogen (DIN), dissolved inorganic phosphorus (DIP) and dissolved silicate (DSi) showed clear terrestrial sources, while ammonia (NH4-N) and dissolved organic nitrogen (DON) were not solely controlled by terrestrial sources. The seasonal variations of NH4-N, DIN, DON, DIP and DSi concentrations were significant, and the interannual variations of DIN, DON, DIP and DSi concentrations showed general decreasing trends from 2016 to 2023. The key factors affecting the seasonal and interannual variations of DIN and DIP concentrations were terrestrial input, aquaculture wastewater discharge, atmospheric deposition, submarine groundwater discharge and macroalgae absorption, while the dominant factor determining the variations of DSi concentrations was terrestrial input. NH4-N and DON concentrations were mainly influenced by aquaculture wastewater discharge and the absorption and release of macroalgae. The high nutrient concentrations in the Subei Shoal throughout the year provided sufficient material basis for the growth of Ulva prolifera in the source area of green tide outbreak.

Bis-benzylisoquinoline alkaloids inhibit African swine fever virus internalization and replication by impairing late endosomal/lysosomal function.

African swine fever (ASF), caused by the African swine fever virus (ASFV), is a highly infectious disease afflicting domestic pigs and wild boars. It exhibits an alarming acute infection fatality rate of up to 100%. Regrettably, no commercial vaccines or specific drugs for combating this disease are currently available. This study evaluated the anti-ASFV activities in porcine alveolar macrophages, 3D4/21 cells, and PK-15 cells of four bis-benzylisoquinoline alkaloids (BBAs): cepharanthine (CEP), tetrandrine, fangchinoline, and iso-tetrandrine. Furthermore, we demonstrated that CEP, which exhibited the highest selectivity index (SI = 81.31), alkalized late endosomes/lysosomes, hindered ASFV endosomal transport, disrupted virus uncoating signals, and thereby inhibited ASFV internalization. Additionally, CEP disrupted ASFV DNA synthesis, leading to the inhibition of viral replication. Moreover, berbamine was labeled with NBD to synthesize a fluorescent probe to study the cellular location of these BBAs. By co-staining with Lyso-Tracker and lysosome-associated membrane protein 1, we demonstrated that BBAs target the endolysosomal compartments for the first time. Our data together indicated that BBAs are a class of natural products with significant inhibitory effects against ASFV infection. These findings suggest their potential efficacy as agents for the prevention and control of ASF, offering valuable references for the identification of potential drug targets.IMPORTANCEThe urgency and severity of African swine fever (ASF) underscore the critical need for effective interventions against this highly infectious disease, which poses a grave threat to domestic pigs and wild boars. Our study reveals the potent anti-African swine fever virus (ASFV) efficacy of bis-benzylisoquinoline alkaloids (BBAs), particularly evident in the absence of progeny virus production under a 5 µM concentration treatment. The structural similarity among cepharanthine, tetrandrine, fangchinoline, and iso-tetrandrine, coupled with their analogous inhibitory stages and comparable selectivity indexes, strongly suggests a shared antiviral mechanism within this drug category. Further investigation revealed that BBAs localize to lysosomes and inhibit the internalization and replication of ASFV by disrupting the endosomal/lysosomal function. These collective results have profound implications for ASF prevention and control, suggesting the potential of the investigated agents as prophylactic and therapeutic measures. Furthermore, our study offers crucial insights into identifying drug targets and laying the groundwork for innovative interventions.

Ionizable STING-Activating Nanoadjuvants Enhance Tumor Immunogenicity and Potentiate Immunotherapy Efficacy in Solid Tumors.

Therapeutic strategies that induce inflammatory responses in immunologically "cold" tumors have the potential to improve immunotherapeutic outcomes. Pharmacologically activating the stimulator of interferon gene (STING) pathway induces innate immunity, subsequently enhancing tumor immunogenicity. Here, we developed a nanoadjuvant with tumor-restricted pharmacology that rapidly activated STING and reshaped the tumor microenvironment. The non-nucleotide STING agonist MSA-2 was chemically engineered with a piperazine motif linked by a saturated hydrocarbon chain of varying lengths to produce ionizable prodrugs that were further developed into nanoadjuvants. Compared with state-of-the-art liposomes, the nanoadjuvant displayed prolonged retention in the circulation and improved intratumoral delivery. In the acidic tumor microenvironment, the nanoadjuvant underwent polyethylene glycol deshielding, enabling efficient extravasation and penetration into tumors. Concomitantly, the STING prodrug escaped from the endo/lysosome compartment to partition into the cytosol for spontaneous esterase-catalyzed drug activation. In mouse models of syngeneic and chemically induced colorectal cancers, nanoparticle treatment provoked robust STING-mediated antitumor immunity, shifting the tumor immune landscape from immunosuppressed to tumoricidal. Additionally, the nanoadjuvant demonstrated antitumor efficacy in triple-negative breast cancer, which was further enhanced by the addition of immune checkpoint inhibitors. Collectively, this study demonstrates the safety and immune-stimulating effects of a STING-activating nanoadjuvant, supporting the clinical evaluation of this STING immunotherapeutic alone and in combination with other immunotherapies. Significance: STING-activating nanoadjuvants rationally engineered using an ionizable prodrug approach for systemic administration are well-tolerated and yield durable antitumor immune responses, providing a potential immunotherapeutic strategy to improve cancer treatment.

Advances in Ubiquitination and Proteostasis in Retinal Degeneration.

Retinal degeneration (RD) is a group of chronic blinding diseases characterised by progressive retinal cell death. As the disease progresses, vision deteriorates due to retinal cell death and impaired retinal integrity, eventually leading to complete loss of vision. Therefore, the function and environmental homeostasis of the retina have an important impact on the pathogenesis and treatment of RD. Ubiquitination, as a complex post-translational modification process, plays an essential role in maintaining retinal homeostasis and normal function. It covalently combines ubiquitin with protein through a series of enzyme-mediated reactions, and participates in cell processes such as gene transcription, cell cycle process, DNA repair, apoptosis and immune response. At the same time, it plays a central role in protein degradation. There are two major protein degradation systems in eukaryotic cells: the ubiquitin-proteasome system and the autophagy-lysosomal system. The protein degradation pathway maintains retinal protein homeostasis by reducing abnormal protein accumulation in the retina through two modes of degradation. Either dysregulation of ubiquitination or disruption of protein homeostasis may lead to the development of RD. This article aims to comprehensively review recent research progress on ubiquitin-related genes, proteins and protein homeostasis in the pathogenesis of RD, and to summarize the potential targeted therapy strategies for it. The review is expected to provide valuable guidance for further development and application of ubiquitination in RD.

Role of cspA on the Preparation of Escherichia coli Competent Cells by Calcium Chloride Method.

One of the fundamental techniques in genetic engineering is the creation of Escherichia coli competent cells using the CaCl2 method. However, little is known about the mechanism of E. coli competence formation. We have previously found that the cspA gene may play an indispensable role in the preparation of E. coli DH5α competent cells through multiomics analysis. In the present study, the cellular localization, physicochemical properties, and function of the protein expressed by the cspA gene were analyzed. To investigate the role of the cspA gene in E. coli transformation, cspA-deficient mutant was constructed by red homologous recombination. The growth, transformation efficiency, and cell morphology of the cspA-deficient strain and E. coli were compared. It was found that there were no noticeable differences in growth and morphology between E. coli and the cspA-deficient strain cultured at 37°C, but the mutant exhibited increased transformation efficiencies compared to E. coli DH5α for plasmids pUC19, pET-32a, and p1304, with enhancements of 2.23, 2.24, and 3.46 times, respectively. It was proved that cspA gene is an important negative regulatory gene in the CaCl2 preparation of competent cells.

Bibliometric analysis of traditional Chinese medicine in the treatment of inflammatory bowel disease.

OBJECTIVE: This study conducts a bibliometric analysis of literature on the treatment of inflammatory bowel disease (IBD) with traditional Chinese medicine (TCM) to explore its research status, hotspots, and development trends, providing ideas and references for further research. METHOD: We screened literature for treating IBD with TCM from the Web of Science Core Collection (WOSCC), and used the VOSviewer software (1.6.18) to discover cooperation among countries, institutions, authors, and information on journals, keywords, etc. We use the CiteSpace software (6.2.R2) to analyze co-citation and burst discovery of references. RESULTS: In all, 440 relevant literature papers were searched and screened from the WOSCC database. The results showed that the number of publications concerning treating IBD with TCM has shown a significant growth in the past decade. China is far ahead in terms of article output, occupying a dominant position. The institution with the most published articles is Nanjing University of Traditional Chinese Medicine. The authors who have published most of the articles are Dai Yancheng, Shi Rui, and Zhou Lian. The Journal of Ethnopharmacology published maximum articles in this field, while Gastroenterology was the most cited journal. Ungaro et al.'s article entitled "Ulcerative colitis" (https://doi.org/10.1016/S0140-6736(16)32126-2), published in The Lancet in 2017 was the most cited study. The high-frequency keywords mainly include ulcerative colitis, inflammation, NF-κB, expression, traditional Chinese medicine, gut microbiota, activation, mice, cells, etc. CONCLUSIONS: The research heat for treating IBD with TCM has risen over the past decade, with studies focusing on three main aspects: clinical studies of TCM, basic pharmacology, and animal experimental research. The research hotspot shifted from pathogenesis, clinical study of TCM, basic pharmacology, and complementary therapies to the study of network pharmacology and the mechanism of action of TCM related to gut microbiota. Network pharmacology and gut microbiota are at the frontiers of research and turning to be the future research trends to provide new insights and ideas for further research for treating IBD with TCM.

Discharge coefficient of vertical sluice gates with broad crested weir under free-submerged orifice flows using best subset regression.

Accurate calculation of flow discharge for sluice gates is essential in irrigation, water supply, and structure safety. The measurement of discharge with the requirement of distinguishing flow regimes is not conducive to application. In this study, a novel approach that considers both free and submerged flow was proposed. The energy-momentum method was employed to derive the coefficient of discharge. Subsequently, the discharge coefficient was determined through the experiment which was performed on the physical model of a vertical sluice gate with a broad-crested weir. Feature engineering, incorporating dimensional analysis, feature construction, and correlation-based selection were performed. The best subset regression method was employed to develop regression equations of the discharge coefficient with the generated features. The derived formula was applied to compute the discharge coefficient in the vertical sluice gate and determine the flow discharge. The accuracy of adopted method was assessed by comparing it with recent studies on submerged flow, and the results demonstrate that the developed approach achieves a high level of accuracy in calculating flow discharge. The coefficient of determination for the calculated flow rate is 0.993, and the root mean square percentage error is 5.04%.

Chemically engineered mTOR-nanoparticle blockers enhance antitumour efficacy.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly prevalent and deadly type of cancer, and although pharmacotherapy remains the cornerstone of treatment, therapeutic outcomes are often unsatisfactory. Pharmacological inhibition of mammalian target of rapamycin (mTOR) has been closely associated with HCC regression. METHODS: Herein, we covalently conjugated AZD8055, a potent mTORC1/2 blocker, with a small panel of unsaturated fatty acids via a dynamically activating linkage to enable aqueous self-assembly of prodrug conjugates to form mTOR nanoblockers. Cell-based experiments were carried out to evaluate the effects of the nanoblocker against hepatocellular carcinoma (HCC) cells. The orthotopic and subcutaneous HCC mouse models were established to examine its antitumour activity. FINDINGS: Among several fatty acids as promoieties, linoleic acid-conjugated self-assembling nanoblocker exhibited optimal size distribution and superior physiochemical properties. Compared with free agents, PEGylated AZD8055 nanoblocker (termed AZD NB) was pharmacokinetically optimized after intravenous administration. In vivo investigations confirmed that AZD NB significantly suppressed tumour outgrowth in subcutaneous HCCLM3 xenograft, Hepatoma-22, and orthotopic Hepa1-6 liver tumour models. Strikingly, treatment with AZD NB, but not free agent, increased intratumour infiltration of IFN-γ+CD8+ T cells and CD8+ memory T cells, suggesting a potential role of the mTOR nanoblocker to remodel the tumour microenvironment. Overall, a single conjugation with fatty acid transformed a hydrophobic mTOR blocker into a systemically injectable nanomedicine, representing a facile and generalizable strategy for improving the therapeutic index of mTOR inhibition-based cancer therapy. INTERPRETATION: The mTOR inhibition by chemically engineered nanoblocker presented here had enhanced efficacy against tumours compared with the pristine drug and thus has the potential to improve the survival outcomes of patients with HCC. Additionally, this new nanosystem derived from co-assembling of small-molecule prodrug entities can serve as a delivery platform for the synergistic co-administration of distinct pharmaceutical agents. FUNDING: This work was supported by the National Natural Science Foundation of China (32171368,81721091), the Zhejiang Provincial Natural Science Foundation of China (LZ21H180001), the Jinan Provincial Laboratory Research Project of Microecological Biomedicine (JNL-2022039c and JNL-2022010B), State Key Laboratory for Diagnosis and Treatment of Infectious Diseases (zz202310), and Natural Science Foundation of Shandong Province (ZR2023ZD59).

Generation of a human iPSC line from a Parkinson's disease patient with a novel CHCHD2 mutation (p.R145Q).

Mutations in CHCHD2 have been reported to be associated with familial Parkinson's disease (PD). We generated a human induced pluripotent stem cell (hiPSC) line by reprogramming dermal fibroblasts from a PD patient harboring a novel CHCHD2 mutation (c.434G > A, p.R145Q). This line exhibited human embryonic stem cell (hESC)-like clonal morphology, expression of undifferentiated stem cell markers, a normal karyotype and trilineage differentiation capacity and thus the potential to serve as a model for further investigating the underlying molecular mechanisms of CHCHD2 function in PD.

Visual analysis of global hemorrhagic fever with renal syndrome research from 1980 to 2022: Based on CiteSpace and VOSviewer.

OBJECTIVE: The development and current state of hemorrhagic fever with renal syndrome (HFRS) over the past 40 years are analyzed in this study, along with explored and discovered the hotspots and frontiers in the field, which serve as the foundation for future investigation. METHODS: CiteSpace and VOSviewer analysis software were used to visually analyze the literature data on HFRS from 1980 to 2022, including the annual number of publications, countries and research institutions, authors, co-cited literature and keywords. RESULTS: The number of pertinent papers published in the field of HFRS displayed an overall upward trend from 1980 to 2022. The United States, China, Germany, Sweden, and France are the top 5 countries in terms of publishing volume, with high intermediate centrality mainly concentrated in Europe and the United States. The top 10 co-occurring keywords were hemorrhagic fever, renal syndrome, infection, virus, epidemic, nephropathia epidemical, disease, hantavirus, outbreak, and transmission. According to keyword cluster analysis, there were 4 main research fields. In the HFRS-related study, there were mainly 21 notable keywords and "Korean hemorrhagic fever" had the highest hemorrhagic value (28.87). CONCLUSION: The United States, China, Germany, Sweden and other countries attached great importance to the HFRS-related research. Moreover, the collaboration between authors and institutions in various collaborator clusters should be strengthened. In recent decades, investigations have focused on the study of viral infection and the clinical symptoms and pathophysiology of HFRS. Future research may concentrate on factors affecting host population distribution and density, such as vaccine development and meteorological factors pertaining to virus transmission.

[Application Progress of Resting-State Functional Magnetic Resonance Imaging in Study of Default Mode Network in Patients with Vascular Cognitive Impairment].

Vascular cognitive impairment（VCI） is a group of syndromes ranging from mild cognitive impairment to dementia caused by cerebrovascular disease, due to the lack of sensitivity and specific biomarkers, it is difficult to identify and diagnose early. Abnormal connectivity is observed in brain regions of patients with vascular cognitive disorders, locates mainly in the default mode network（DMN）, and changes in their abnormal functional connectivity correlated with the degree of patients' cognitive impairment. Resting-state functional magnetic resonance imaging(rs-fMRI) is a commonly used method to detect the internal activity of the brain at resting state. The use of various rs-fMRI to study abnormal changes in the DMN in patients with VCI is useful to further investigate the pathogenesis of VCI and provide an objective basis for imaging. This article mainly reviews the application of rs-fMRI in the DMN in patients with VCI, bringing new perspectives for the correct diagnosis and assessment of VCI.

METTL3-mediated HSPA9 m6A modification promotes malignant transformation and inhibits cellular senescence by regulating exosomal mortalin protein in cervical cancer.

The role of RNA methyltransferase 3 (METTL3) in tumor progression when tethered to aberrantly expressed oncogenes remains unknown. In especial, the correlation between cervical cancer (CCa)-derived exosomes and m6A methylation in malignant traits of cervical epithelium is currently elusive. Mortalin expression was found to be up-regulated in plasma exosomes isolated from CCa patients. Furthermore, mortalin gained increased mRNA stability and enhanced translation efficiency via the m6A methylation in the HSPA9 mRNA 3'UTR, which was catalysed by METTL3 in CCa cells. Exosomal mortalin overexpression significantly promoted the proliferation, migration and invasion of CCa both in vitro and in vivo. Additionally, exosome-encapsulated mortalin suppressed cellular senescence and facilitated malignant transformation by blocking nuclear transport of p53, thereby preventing the p53-Gadd45A interaction and resulting in inactivation of p53. Our studies demonstrated the significant role of METTL3 mediated exosomal mortalin in malignant transformation and cellular senescence suppression of CCa. Exosomal mortalin could clinically serve as a potential early-diagnosis biomarker and therapeutic target for CCa given its abundance and propensity to be found.

The inhibition of YTHDF3/m6A/LRP6 reprograms fatty acid metabolism and suppresses lymph node metastasis in cervical cancer.

The lipid synthesis of fatty acid (FA) represents a significant hallmark in the occurrence and progression of malignant tumor, which are associated with lymph node (LN) metastasis. Elucidation of the molecular mechanisms underlying LN metastasis could provide therapeutic strategies for cervical cancer (CCa). N6-Methyladenosine (m6A), the most prevalent and abundant RNA modification, exerts specific regulatory control over a series of oncogene expressions. This study demonstrated a clinical correlation between the upregulation of the m6A reader YTHDF3 and LN metastasis, thereby contributing to poor overall survival probability (OS) among CCa patients. The mechanistic investigation revealed that SREBF1 transcriptionally activated YTHDF3 expression by binding to its promoter. Functional experiments demonstrated that the upregulation of YTHDF3 significantly enhanced the in vitro proliferative, migratory, and invasive capacities of CCa cells, while also promoting lymphangiogenesis and facilitating LN metastasis in vivo. Mechanistically, the upregulation of LRP6 through YTHDF3-mediated m6A modification resulted in increased expression of FASN and ACC1, leading to both lipolysis of lipid droplets and synthesis of free fatty acid. Ultimately, this promoted fatty acid metabolism and enhanced LN metastasis by activating the LRP6-YAP-VEGF-C axis, which could induce lymphangiogenesis in CCa. Our study highlighted that YTHDF3 can serve as a promising therapeutic target and predictive biomarker for CCa patients with LN metastasis.

NAT10/ac4C/FOXP1 Promotes Malignant Progression and Facilitates Immunosuppression by Reprogramming Glycolytic Metabolism in Cervical Cancer.

Immunotherapy has recently emerged as the predominant therapeutic approach for cervical cancer (CCa), driven by the groundbreaking clinical achievements of immune checkpoint inhibitors (ICIs), such as anti-PD-1/PD-L1 antibodies. N4-acetylcytidine (ac4C) modification, catalyzed by NAT10, is an important posttranscriptional modification of mRNA in cancers. However, its impact on immunological dysregulation and the tumor immunotherapy response in CCa remains enigmatic. Here, a significant increase in NAT10 expression in CCa tissues is initially observed that is clinically associated with poor prognosis. Subsequently, it is found that HOXC8 activated NAT10 by binding to its promoter, thereby stimulating ac4C modification of FOXP1 mRNA and enhancing its translation efficiency, eventually leading to induction of GLUT4 and KHK expression. Moreover, NAT10/ac4C/FOXP1 axis activity resulted in increased glycolysis and a continuous increase in lactic acid secretion by CCa cells. The lactic acid-enriched tumor microenvironment (TME) further contributed to amplifying the immunosuppressive properties of tumor-infiltrating regulatory T cells (Tregs). Impressively, NAT10 knockdown enhanced the efficacy of PD-L1 blockade-mediated tumor regression in vivo. Taken together, the findings revealed the oncogenic role of NAT10 in initiating crosstalk between cancer cell glycolysis and immunosuppression, which can be a target for synergistic PD-1/PD-L1 blockade immunotherapy in CCa.

Chemically programmed STING-activating nano-liposomal vesicles improve anticancer immunity.

The often immune-suppressive tumor microenvironment (TME) may hinder immune evasion and response to checkpoint blockade therapies. Pharmacological activation of the STING pathway does create an immunologically hot TME, however, systemic delivery might lead to undesired off-target inflammatory responses. Here, we generate a small panel of esterase-activatable pro-drugs based on the structure of the non-nucleotide STING agonist MSA-2 that are subsequently stably incorporated into a liposomal vesicle for intravenous administration. The pharmacokinetic properties and immune stimulatory capacity of pro-drugs delivered via liposomes (SAProsomes) are enhanced compared to the free drug form. By performing efficacy screening among the SAProsomes incorporating different pro-drugs in syngeneic mouse tumor models, we find that superior therapeutic performance relies on improved delivery to the desired tumor and lymphoid compartments. The best candidate, SAProsome-3, highly stimulates secretion of inflammatory cytokines and creates a tumoricidal immune landscape. Notably, upon application to breast cancer or melanoma mouse models, SAProsome-3 elicits durable remission of established tumors and postsurgical tumor-free survival while decreasing metastatic burden without significant systemic toxicity. In summary, our work establishes the proof of principle for a better targeted and more efficient and safe STING agonist therapy.

High internal phase Pickering emulsions stabilised by ultrasound-induced soy protein-ß-glucan-catechin complex nanoparticles to enhance the stability and bioaccessibility of curcumin.

AIMS: To evaluate the potential applications of soy protein-glucan-catechin (SGC) complexes prepared with different ultrasound times in stabilising high internal phase Pickering emulsion (HIPPE) and delivering curcumin. METHODS: The SGC complexes were characterised by particle size, morphology, zeta potential, Fourier transform infra-red, and fluorescence spectroscopy. Formation and stability of curcumin emulsions were monitored by droplet size, microstructure, rheological property, lipid oxidation, and in vitro digestion. RESULTS: Short-time ultrasound-induced complexes (SGC-U15) exhibited a small size and wettability of ∼82.5°. The chemical stability and bioaccessibility of curcumin was greatly improved by SGC-U15-stabilised HIPPEs, even after 70 days of storage, heating at 100 °C for 30 min, ultraviolet irradiation for 120 min, and in vitro digestion, owing to the formation of elastic gel-like structure at the oil/water interfaces. CONCLUSION: Our findings may contribute to the design of emulsion-based delivery systems using ultrasound-induced protein-polysaccharide-polyphenol complexes.

Long-term variation in nutrients in the South Yellow Sea in response to anthropogenic inputs.

Based on historical data from 1976 to 2019, the effects of anthropogenic activities on long-term changes in nutrients and their ecological effects in the South Yellow Sea were investigated. The dissolved inorganic nitrogen (DIN) concentrations increased continuously from 1990 until the mid-2000s, followed by a shift from an upward trend to a downward trend. The phosphate (PO4-P) and silicate (SiO3-Si) concentrations also showed obvious interannual variations throughout the study period. The concentrations of DIN, PO4-P and SiO3-Si have decreased significantly in recent decade and more. These changes mainly resulted from the reduction in terrestrial input, while the main reason for the decrease in DIN and PO4-P concentrations is the reduction in anthropogenic input. The long-term nutrient changes in the South Yellow Sea have potential ecological impacts on green tide features.

Triple-Combination Immunogenic Nanovesicles Reshape the Tumor Microenvironment to Potentiate Chemo-Immunotherapy in Preclinical Cancer Models.

Immune checkpoint blockade (ICB) therapies have had a tremendous impact on cancer therapy. However, most patients harbor a poorly immunogenic tumor microenvironment (TME), presenting overwhelming de novo refractoriness to ICB inhibitors. To address these challenges, combinatorial regimens that employ chemotherapies and immunostimulatory agents are urgently needed. Here, a combination chemoimmunotherapeutic nanosystem consisting of a polymeric monoconjugated gemcitabine (GEM) prodrug nanoparticle decorated with an anti-programmed cell death-ligand 1 (PD-L1) antibody (αPD-L1) on the surface and a stimulator of interferon genes (STING) agonist encapsulated inside is developed. Treatment with GEM nanoparticles upregulates PD-L1 expression in ICB-refractory tumors, resulting in augmented intratumor drug delivery in vivo and synergistic antitumor efficacy via activation of intratumor CD8+ T cell responses. Integration of a STING agonist into the αPD-L1-decorated GEM nanoparticles further improves response rates by transforming low-immunogenic tumors into inflamed tumors. Systemically administered triple-combination nanovesicles induce robust antitumor immunity, resulting in durable regression of established large tumors and a reduction in the metastatic burden, coincident with immunological memory against tumor rechallenge in multiple murine tumor models. These findings provide a design rationale for synchronizing STING agonists, PD-L1 antibodies, and chemotherapeutic prodrugs to generate a chemoimmunotherapeutic effect in treating ICB-nonresponsive tumors.