Transcription factor OsbZIP10 modulates rice grain quality by regulating OsGIF1.

Understanding and optimizing the process of grain filling helps the quest to maximize rice (Oryza sativa L.) seed yield and quality, yet the intricate mechanisms at play remain fragmented. Transcription factors (TFs) are major players in the gene networks underlying the grain filling process. Here, we employed grain incomplete filling (OsGIF1)/cell wall invertase 2, a key gene involved in grain filling, to explore its upstream TFs and identified a bZIP family TF, OsbZIP10, to be a transcriptional activator of OsGIF1. Rice grains of the knockouts of OsbZIP10 showed increased white-core rates but lower amylose content (AC), leading to better eating and cooking qualities in all genetic backgrounds investigated, though the impact of mutations in OsbZIP10 on grain weight depended on genetic background. Multi-omics analyses suggested that, in addition to OsGIF1, multiple genes involved in different biological processes contributing to grain filling were targeted by OsbZIP10, including OsAGPS1, a gene encoding the ADP-Glc pyrophosphorylase (AGPase) small subunit, and genes contributing to homeostasis of reactive oxygen species. Distinct genetic make-up was observed in OsbZIP10 between japonica and indica rice varieties, with the majority varieties of each subspecies belonging to two different haplotypes that were closely associated with AC. Overexpressing the haplotype linked to high-AC in the low-AC genetic background increased AC. Overall, this study sheds crucial light on the significance of the OsbZIP10-OsGIF1 module in the determination of rice grain quality, offering a potential avenue for genetic engineering of rice to produce seeds with tailored attributes.

N-acyl homoserine lactones (AHLs) enhanced removal of cadmium and other pollutants by algae-bacteria consortia.

Signal transduction is an important mode of algae-bacteria interaction, in which bacterial quorum sensing (QS) may affect microalgal growth and metabolism. Currently, little is known whether acyl homoserine lactones (AHLs) released by bacteria can affect the pollutant removal by algae-bacteria consortia (ABC). In this study, we constructed ABC using Chlorella vulgaris (Cv) with two AHLs-producing bacteria and investigated their performance in the removal of multiple pollutants, including chemical oxygen demand (COD), total nitrogen (TN), phosphorus (P), and cadmium (Cd). The AHLs-producing bacteria, namely Agrobacterium sp. (Ap) and Ensifer adherens (Ea), were capable of forming a symbiosis with C. vulgaris. Consortia of Cv and Ap with ratio of 2:1 (Cv2-Ap1) showed the optimal growth promotion and higher removal of Cd, COD, TN, and P compared to the C. vulgaris monoculture. Cv2-Ap1 ABC removed 36.1-47.5% of Cd, 94.5%-94.6% COD, 37.1%-56.0% TN, and 90.4%-93.5% P from the culture medium. In addition, increase of intracellular neutral lipids and extracellular protein, as well as the types of functional groups on cell surface contributed to Cd removal and tolerance in the Cv2-Ap1 ABC. Six AHLs were detected in the Cv2-Ap1 culture. Among these, 3OC8-HSL and 3OC12-HSL additions promoted the ABC growth and enhanced their Cd accumulation. These findings may contribute to further understanding of AHL-mediated communication between algae and bacteria and provide support bioremediation efforts of metal-containing wastewater.

Disinfectant polyhexamethylene guanidine triggered simultaneous efflux pump antibiotic- and metal-resistance genes propagation during sludge anaerobic digestion.

The environmental transmission of antibiotic resistance genes (ARGs) and metal resistance genes (MRGs) exerted devastating threats to global public health, and their interactions with other emerging contaminants (ECs) have raised increasing concern. This study investigated that the abundances of ARGs and MRGs with the predominant type of efflux pump were simultaneously increased (8.4-59.1%) by disinfectant polyhexamethylene guanidine (PHMG) during waste activated sludge (WAS) anaerobic digestion. The aggregation of the same microorganisms (i.e., Hymenobacter and Comamonas) and different host bacteria (i.e., Azoarcus and Thauera) were occurred upon exposure to PHMG, thereby increasing the co-selection and propagation of MRGs and ARGs by vertical gene transfer. Moreover, PHMG enhanced the process of horizontal gene transfer (HGT), facilitating their co-transmission by the same mobile genetic elements (20.2-223.7%). Additionally, PHMG up-regulated the expression of critical genes (i.e., glnB, trpG and gspM) associated with the HGT of ARGs and MRGs (i.e., two-component regulatory system and quorum sensing) and exocytosis system (i.e., bacterial secretion system). Structural equation model analysis further verified that the key driver for the simultaneous enrichment of ARGs and MRGs under PHMG stress was microbial community structure. The study gives new insights into the aggravated environmental risks and mechanisms of ECs in sludge digestion system, providing guidance for subsequent regulation and control of ECs.

Pipersarmenoids, new amide alkaloids from Piper sarmentosum.

A chemical investigation of the aerial parts of Piper sarmentosum resulted in the isolation and identification of 14 amide alkaloids, including three new amide alkaloids, pipersarmenoids A - C (1-3), three new natural amide alkaloids, pipersarmenoids D - F (4-6), and 8 known analogues, N-p-coumaroyltyramine (7), piperlotine C (8), piperlotine D (9), pellitorine (10), sarmentine (11), aurantiamide acetate (12), 1-cinnamoyl pyrrolidine (13) and sarmentamide B (14). Their structures were determined by spectroscopic analysis including HRESIMS and 1D and 2D NMR. The cytotoxicity, neuroinflammation-inhibiting and acetylcholinesterase (AChE) inhibitory activities of those compounds were tested. Compounds 1, 2 and 12 inhibited NO production induced by LPS in BV2 cells with IC50 values of 9.36, 12.53 and 10.77 µM, respectively. Moreover, 1, 2, 7 and 11 showed moderate inhibitory activity on AChE with IC50 values ranging from 37.56 to 48.84 µM.

Intertwined role of mechanism identification by DFT-XAFS and engineering considerations in the evolution of P adsorbents.

Adsorption method exhibits promising potential in effectively removal of phosphate from wastewater, yet it faces tremendous challenges in practical application. Limited comprehension of adsorption mechanisms and the lack of evaluation method for scaling up application are the two main obstacles. To fully realize the practical application of P adsorbents, we reviewed advanced tools, including density functional theory (DFT) and/or X-ray absorption fine structure (XAFS) to elucidate mechanisms, underscored the significance of thermodynamics and kinetics in engineering design, and proposed strategies for regenerating and reusing P adsorbents. Specifically, we delved into the utilization of DFT and XAFS to gain insights into adsorption mechanisms, focusing on active site verification and molecular interaction configurations. Additionally, we explored precise calculation methods for adsorption thermodynamics and adsorption kinetics, encompassing thermodynamic equilibrium constants, reactor selection, and the regeneration, recovery, and disposal of P adsorbents. Our comprehensive review aims to serve as a guiding light in advancing the development of highly efficient P adsorbents for engineering applications.

Streamlined Full-Length Total RNA Sequencing of Paraformaldehyde-Fixed Brain Tissues.

Paraformaldehyde (PFA) fixation is the preferred method for preserving tissue architecture for anatomical and pathological observations. Meanwhile, PFA reacts with the amine groups of biomolecules to form chemical cross-linking, which preserves RNA within the tissue. This has great prospects for RNA sequencing to characterize the molecular underpinnings after anatomical and pathological observations. However, RNA is inaccessible due to cross-linked adducts forming between RNA and other biomolecules in prolonged PFA-fixed tissue. It is also difficult to perform reverse transcription and PCR, resulting in low sequencing sensitivity and reduced reproducibility. Here, we developed a method to perform RNA sequencing in PFA-fixed tissue, which is easy to use, cost-effective, and allows efficient sample multiplexing. We employ cross-link reversal to recover RNA and library construction using random primers without artificial fragmentation. The yield and quality of recovered RNA significantly increased through our method, and sequencing quality metrics and detected genes did not show any major differences compared with matched fresh samples. Moreover, we applied our method for gene expression analysis in different regions of the mouse brain and identified unique gene expression profiles with varied functional implications. We also find significant dysregulation of genes involved in Alzheimer's disease (AD) pathogenesis within the medial septum (MS)/vertical diagonal band of Broca (VDB) of the 5×FAD mouse brain. Our method can thus increase the performance of high-throughput RNA sequencing with PFA-fixed samples and allows longitudinal studies of small tissue regions isolated by their in situ context.

Natural mineral and industrial solid waste-based adsorbent for perfluorooctanoic acid and perfluorooctane sulfonate removal from surface water: Advances and prospects.

PER: and polyfluorinated alkyl substances, especially perfluorooctanoic acid and perfluorooctane sulfonic acid (PFOX), have attracted considerable attention lately because of their widespread occurrence in aquatic environment and potential biological toxicity to animals and human beings. The development of economical, efficient, and engineerable adsorbents for removing PFOX in water has become one of the research focuses. This review summarized the recent progress on natural mineral and industrial solid based adsorbent (NM&ISW-A) and removal mechanisms concerning PFOX onto NM&ISW-A, as well as proposed the current challenges and future perspectives of using NM&ISW-A for PFOX removal in water. Kaolinite and montmorillonite are usually used as model clay minerals for PFOX removal, and have been proved to adsorb PFOX by ligand exchange and electrostatic attraction. Fe-based minerals, such as goethite, magnetite, and hematite, have better PFOX adsorption capacity than clay minerals. The adsorbent prepared from industrial solid waste by high temperature roasting has great potential application prospects. Fabricating nanomaterials, amination modification, surfactant modification, fluorination modification, developing versatile composites, and designing special porous structure are beneficial to improve the adsorption performance of PFOX onto NM&ISW-A by enhancing the specific surface area, positive charge, and hydrophobicity. Electrostatic interaction, hydrophobic interaction, hydrogen bond, ligand and ion exchange, and self-aggregation (formation of micelle or hemimicelle) are the main adsorption mechanisms of PFOX by NM&ISW-A. Among them, electrostatic and hydrophobic interactions play a considerable role in the removal of PFOX by NM&ISW-A. Therefore, NM&ISW-A with electrostatic functionalities and considerable hydrophobic segments enables rapid, efficient, and high-capacity removal of PFOX. The future directions of NM&ISW-A for PFOX removal include the preparation and regeneration of engineerable NM&ISW-A, the development of coupling technology for PFOX removal based on NM&ISW-A, the in-depth research on adsorption mechanism of PFOX by NM&ISW-A, as well as the development of NM&ISW-A for PFOX alternatives removal. This review paper would be helpful the comprehensive understanding of NM&ISW-A potential for PFOX removal and the PFOX removal mechanisms, and identifies the gaps for future research and development.

A united framework modeling of spatial-temporal characteristics for county-level agricultural carbon emission with an application to Hunan in China.

Effectively tackling extreme climate change requires sound knowledge about carbon emissions and their driving forces. Currently, agricultural carbon emission assessment often deals with its inventory, efficiency, determinants, and response independently, which will leave out the complex interactions among its various components, thus there is a lack of comprehensive, scalable, comparable explanations for agricultural carbon emissions. Herein, we introduce an integrated agricultural carbon emission assessment framework (IEDR): Inventory (I) × Efficiency (E) × Determinants (D) × Response (R), which was then applied to an illustration for the county-level agricultural carbon emissions in Hunan Province, China. Results show that: (1) Agricultural carbon emission inventory (ACEI) increased from 20.06 × 106 tC in 2006 to 21.99 × 106 tC in 2014 and decreased to 19.07 × 106 tC by 2020, depicting a fluctuating trend. Meanwhile, there was remarkable spatial heterogeneity, with higher ACEI in the North and South than in the East and West. (2) Agricultural carbon emission efficiency (ACEE) increased from 0.8520 in 2006 to 0.8992 in 2020, depicting a growing trend driven by technological progress. Spatially distributed in contrast to ACEI, regions with higher ACEE were located in the eastern and western areas. (3) ACEI was negatively correlated with ACEE (-0.657), indicating that increasing ACEE is a key strategy for reducing emissions. (4) The natural environment, rural development level, and policy support had critical impacts on ACEE and ACEI. In particular, the cultivated area and rural water affairs development were significant influences on ACEE and ACEI. Given the externalities of carbon emissions and its important public goods characteristics of the atmosphere, local carbon issues are also global concerns. Therefore, the case study of the IEDR model not only validates this theoretical paradigm and realizes regional responsibility for global carbon reduction but also supports and expands the theoretical and empirical corpus in the field of agricultural carbon emissions and efficiency, providing insights and references for other global regions facing similar challenges.

Spatial distance between tumor and lymphocyte can predict the survival of patients with resectable lung adenocarcinoma.

Background and objective: Spatial interaction between tumor-infiltrating lymphocytes (TILs) and tumor cells is valuable in predicting the effectiveness of immune response and prognosis amongst patients with lung adenocarcinoma (LUAD). Recent evidence suggests that the spatial distance between tumor cells and lymphocytes also influences the immune responses, but the distance analysis based on Hematoxylin and Eosin (H&E) -stained whole-slide images (WSIs) remains insufficient. To address this issue, we aim to explore the relationship between distance and prognosis prediction of patients with LUAD in this study. Methods: We recruited patients with resectable LUAD from three independent cohorts in this multi-center study. We proposed a simple but effective deep learning-driven workflow to automatically segment different cell types in the tumor region using the HoVer-Net model, and quantified the spatial distance (DIST) between tumor cells and lymphocytes based on H&E-stained WSIs. The association of DIST with disease-free survival (DFS) was explored in the discovery set (D1, n = 276) and the two validation sets (V1, n = 139; V2, n = 115). Results: In multivariable analysis, the low DIST group was associated with significantly better DFS in the discovery set (D1, HR, 0.61; 95 % CI, 0.40-0.94; p = 0.027) and the two validation sets (V1, HR, 0.54; 95 % CI, 0.32-0.91; p = 0.022; V2, HR, 0.44; 95 % CI, 0.24-0.81; p = 0.009). By integrating the DIST with clinicopathological factors, the integrated model (full model) had better discrimination for DFS in the discovery set (C-index, D1, 0.745 vs. 0.723) and the two validation sets (V1, 0.621 vs. 0.596; V2, 0.671 vs. 0.650). Furthermore, the computerized DIST was associated with immune phenotypes such as immune-desert and inflamed phenotypes. Conclusions: The integration of DIST with clinicopathological factors could improve the stratification performance of patients with resectable LUAD, was beneficial for the prognosis prediction of LUAD patients, and was also expected to assist physicians in individualized treatment.

Multiple non-covalent-interaction-directed supramolecular double helices: the orthogonality of hydrogen, halogen and chalcogen bonding.

In this study, a benzoselenadiazole- and pyridine-bifunctionalized hydrogen-bonded arylamide foldamer was synthesized. A co-crystallization experiment with 1,4-diiodotetrafluorobenzene showed that a new type of supramolecular double helices, which were induced by three orthogonal interactions, namely, three-center hydrogen bonding (O⋯H⋯O), I⋯N halogen bonding and Se⋯N chalcogen bonding, have been constructed in the solid state. This work presents a novel instance of multiple non-covalent interactions that work together to construct supramolecular architectures.

Targeting STING in dendritic cells alleviates psoriatic inflammation by suppressing IL-17A production.

Psoriasis is a common chronic inflammatory skin disease driven by the aberrant activation of dendritic cells (DCs) and T cells, ultimately leading to increased production of cytokines such as interleukin (IL)-23 and IL-17A. It is established that the cGAS-STING pathway is essential for psoriatic inflammation, however, the specific role of cGAS-STING signaling in DCs within this context remains unclear. In this study, we demonstrated the upregulation of cGAS-STING signaling in psoriatic lesions by analyzing samples from both clinical patients and imiquimod (IMQ)-treated mice. Using a conditional Sting-knockout transgenic mouse model, we elucidated the impact of cGAS-STING signaling in DCs on the activation of IL-17- and IFN-γ-producing T cells in psoriatic inflammation. Ablation of the Sting hampers DC activation leads to decreased numbers of IL-17-producing T cells and Th1 cells, and thus subsequently attenuates psoriatic inflammation in the IMQ-induced mouse model. Furthermore, we explored the therapeutic potential of the STING inhibitor C-176, which reduces psoriatic inflammation and enhances the anti-IL-17A therapeutic response. Our results underscore the critical role of cGAS-STING signaling in DCs in driving psoriatic inflammation and highlight a promising psoriasis treatment.

Comparative Bleeding Risk of Brand Vs Generic Rivaroxaban in Elderly Inpatients with Atrial Fibrillation.

Objective: Atrial fibrillation (AF) is the most common abnormal heart rhythm in elderly patients. Rivaroxaban has been widely used for stroke prevention. The anticoagulant response to rivaroxaban increases with age, which may make elderly patients susceptible to adverse outcomes resulting from small differences in bioavailability between generic and brand products. Methods: We designed a cohort study of ≥65-year-old inpatients with AF. Sociodemographic and laboratory measures of qualified patients who received brand or generic rivaroxaban for at least 72 hours at the study hospital from January 2021 to June 2023 were collected retrospectively. The primary outcome was the incidence of bleeding. Results: A total of 1008 qualifying patients were included for analysis, with 626 (62.1%) receiving brand rivaroxaban and 382 (37.9%) receiving generic rivaroxaban. After propensity score matching and weighting to account for confounders, the odds ratios comparing brand vs generic rivaroxaban (95% confidence intervals) for the bleeding was 1.15 (0.72-1.82). Results from subgroup analyses of patients with age ≥85, HAS-BLED score ≥ 3, containment of antiplatelet drugs, and female patients were consistent with the primary analysis. Conclusion: It provides evidence regarding the clinical safety outcome of generic rivaroxaban in the elderly AF population that may be particularly susceptible to adverse outcomes resulting from small allowable differences in pharmacokinetics.

miR-1246-overexpressing exosomes improve UVB-induced photoaging by activating autophagy via suppressing GSK3ß.

Stem cell paracrine has shown potential application in skin wound repair and photoaging treatment. Our previous study demonstrated that miR-1246-overexpressing Exosomes (OE-EXs) isolated from adipose-derived stem cells (ADSCs) showed superior photo-protecting effects on UVB-induced photoaging than that of the vector, however, the underlying mechanism was unclear. The simultaneous bioinformatics analysis indicated that miR-1246 showed potential binding sites with GSK3ß which acted as a negative regulator for autophagy. This study was aimed to explore whether OE-EXs ameliorate skin photoaging by activating autophagy via targeting GSK3ß. The results demonstrated that OE-EXs significantly decreased GSK3ß expression, enhanced autophagy flux and autophagy-related proteins like LC3II, while suppressed p62 expression. Meanwhile, OE-EXs markedly reversed the levels of intracellular ROS, MMP-1, procollagen type I and DNA damage in human skin fibroblasts caused by UVB irradiation, but the ameliorating effects were significantly inhibited when 3-Methyladenine (3-MA) was introduced to block the autophagy pathway. Further, OE-EXs could reverse UVB-induced wrinkles, epidermal hyperplasia, and collagen fibers reduction in Kunming mice, nevertheless, the therapeutical effects of OE-EXs were attenuated when it was combinative treated with 3-MA. In conclusion, OE-EXs could cure UVB induced skin photoaging by activating autophagy via targeting GSK3ß.

Maternal circadian rhythm disruption affects neonatal inflammation via metabolic reprograming of myeloid cells.

Disruption of circadian rhythm during pregnancy produces adverse health outcomes in offspring; however, the role of maternal circadian rhythms in the immune system of infants and their susceptibility to inflammation remains poorly understood. Here we show that disruption of circadian rhythms in pregnant mice profoundly aggravates the severity of neonatal inflammatory disorders in both male and female offspring, such as necrotizing enterocolitis and sepsis. The diminished maternal production of docosahexaenoic acid (DHA) and the impaired immunosuppressive function of neonatal myeloid-derived suppressor cells (MDSCs) contribute to this phenomenon. Mechanistically, DHA enhances the immunosuppressive function of MDSCs via PPARγ-mediated mitochondrial oxidative phosphorylation. Transfer of MDSCs or perinatal supplementation of DHA relieves neonatal inflammation induced by maternal rhythm disruption. These observations collectively demonstrate a previously unrecognized role of maternal circadian rhythms in the control of neonatal inflammation via metabolic reprograming of myeloid cells.

LaMg6Ga6S16: a chemical stable divalent lanthanide chalcogenide.

Divalent lanthanide inorganic compounds can exhibit unique electronic configurations and physicochemical properties, yet their synthesis remains a great challenge because of the weak chemical stability. To the best of our knowledge, although several lanthanide monoxides epitaxial thin films have been reported, there is no chemically stable crystalline divalent lanthanide chalcogenide synthesized up to now. Herein, by using octahedra coupling tetrahedra single/double chains to construct an octahedral crystal field, we synthesized the stable crystalline La(II)-chalcogenide, LaMg6Ga6S16. The nature of the divalent La2+ cations can be identified by X-ray photoelectron spectroscopy, X-ray absorption near-edge structure and electron paramagnetic resonance, while the stability is confirmed by the differential thermal scanning, in-situ variable-temperature powder X-ray diffraction and a series of solid-state reactions. Owing to the particular electronic characteristics of La2+(5d1), LaMg6Ga6S16 displays an ultrabroad-band green emission at 500 nm, which is the inaugural instance of La(II)-based compounds demonstrating luminescent properties. Furthermore, as LaMg6Ga6S16 crystallizes in the non-centrosymmetric space group, P-6, it is the second-harmonic generation (SHG) active, possessing a comparable SHG response with classical AgGaS2. In consideration of its wider band gap (Eg = 3.0 eV) and higher laser-induced damage threshold (5×AgGaS2), LaMg6Ga6S16 is also a promising nonlinear optical material.

An FOF1-ATPase motor-embedded chromatophore as a nanorobot for overcoming biological barriers and targeting acidic tumor sites.

Despite the booming progress of anticancer nanomedicines in the past two decades, precise tumor-targetability and sufficient tumor-accumulation are less successful and still require further research. To tackle this challenge, herein we present a biomolecular motor (FOF1-ATPase)-embedded chromatophore as nanorobot to efficiently overcome biological barriers, and thoroughly investigate its chemotactic motility, tumor-accumulation ability and endocytosis. Chromatophores embedded with FOF1-ATPase motors were firstly extracted from Thermus thermophilus, then their properties were fully characterized. Specifically, two microfluidic platforms (laminar flow microchip and tumor microenvironment (TME) microchip) were designed and developed to fully investigate the motility, tumor-accumulation ability and endocytosis of the chromatophore nanorobot (CN). The results from the laminar flow microchip indicated that the obtained CN possessed the strongly positive chemotaxis towards protons. And the TME microchip experiments verified that the CN had a desirable tumor-accumulation ability. Cellular uptake experiments demonstrated that the CN efficiently promoted the endocytosis of the fluorescence DiO into the HT-29 cells. And the in vivo studies revealed that the intravenously administered CN exhibited vigorous tumor-targetability and accumulation ability as well as highly efficient antitumor efficacy. All the results suggested that FOF1-ATPase motors-embedded CN could be promising nanomachines with powerful self-propulsion for overcoming physiological barriers and tumor-targeted drug delivery. STATEMENT OF SIGNIFICANCE: In this study, we demonstrated that FOF1-ATPase-embedded chromatophore nanorobots exhibit a strong proton chemotaxis, which not only plays a key role in tumor-targetability and accumulation, but also promotes tumor tissue penetration and internalization. The results of in vitro and in vivo studies indicated that drug-loaded chromatophore nanorobots are capable to simultaneously accomplish tumor-targeting, accumulation, penetration and internalization for enhanced tumor therapy. Our study provides a fundamental basis for further study on FOF1-ATPase-embedded chromatophore as tumor-targeting drug delivery systems that have promising clinical applications. It offers a new and more efficient delivery vehicle for cancer related therapeutics.

Multiple Immunomodulatory Strategies Based on Targeted Regulation of Proprotein Convertase Subtilisin/Kexin Type 9 and Immune Homeostasis against Hepatocellular Carcinoma.

Immunotherapy is the most promising systemic therapy for hepatocellular carcinoma. However, the outcome remains poor. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a role in altering cell-surface protein levels, potentially undermining the efficacy of immunotherapy against tumors. This highlights its potential as a target for antitumor therapy. Herein, CaCO3-based nanoparticles coencapsulated with DOX, an immunogenic cell death (ICD) inducer, and evolocumab was developed to enhanced the efficacy of immunotherapy. The obtained DOX/evolocumab-loaded CaCO3 nanoparticle (named DECP) exhibits a good capacity of acid neutralization and causes ICD of cancer cells. In addition, DECP is able to evaluate the cell-surface level of MHC-I, a biomarker that correlates positively with patients' overall survival. Upon intravenous injection, DECP accumulates within the tumor site, leading to growth inhibition of hepa1-6 bearing subcutaneous tumors. Specifically, DECP treatment causes augmented ratios of matured dendritic cells, tumor-infiltrating CD8+ T cells and natural killing cells, while concurrently depleting Foxp3+ regulatory T cells. Peritumoral delivery of DECP enhances the immune response of distant tumors and exhibits antitumor effects when combined with intravenous αPD-L1 therapy in a bilateral tumor model. This study presents CaCO3-based nanoparticles with multiple immunomodulatory strategies against hepatocellular carcinoma by targeting PCSK9 inhibition and modulating immune homeostasis in the unfavorable TME.

Characteristic analysis and fermentation optimization of a novel Aureobasidium pullulans RM1603 with high pullulan yield.

A high-yielding microbial polysaccharide-producing strain, named RM1603, was isolated from rhizosphere soil and identified by morphological and phylogenetic analysis. The extracellular polysaccharides (EPS) were identified by thin-layer chromatography and infrared spectroscopy. The fermentation conditions were optimized by single factor experiments in shake flasks and a 5-L fermentor. The results of morphological and phylogenetic tree analysis showed that RM1603 was a strain of Aureobasidium pullulans. Its microbial polysaccharide was identified as pullulan, and the EPS production capacity reached 33.07 ± 1.03 g L-1 in shake flasks. The fermentation conditions were optimized in a 5-L fermentor, and were found to encompass an initial pH of 6.5, aeration rate of 2 vvm, rotor speed of 600 rpm, and inoculum size of 2 %. Under these conditions, the pullulan yield of RM1603 reached 62.52 ± 0.24 g L-1. Thus, this study contributes RM1603 as a new isolation with high-yielding pullulan and potential application value in biotechnology.

Partial root-zone drying subsurface drip irrigation increased the alfalfa quality yield but decreased the alfalfa quality content.

Water shortage seriously restricts the development of grassland agriculture in arid land and dramatically impacts alfalfa (Medicago sativa L.) quality content and hay yield. Reasonable irrigation methods have the potential to enhance the alfalfa quality content, hay yield, and thus quality yield. Whether partial root-zone drying subsurface drip irrigation (PRDSDI) improves the alfalfa quality yield, quality content, and hay yield is still unknown compared with conventional subsurface drip irrigation (CSDI). The effects of PRDSDI compared with that of CSDI and the interaction with irrigation volume (10 mm/week, 20 mm/week, and 30 mm/week) on the alfalfa quality yield were investigated in 2017-2018 and explained the change in quality yield with the alfalfa quality content and hay yield. Here, the results showed that PRDSDI did not increase the alfalfa quality yield in 2 years. PRDSDI significantly increased acid detergent fiber by 13.3% and 12.2% in 2018 with 10-mm and 20-mm irrigation volumes and neutral detergent fiber by 16.2%, 13.2%, and 12.6% in 2017 with 10-mm, 20-mm, and 30-mm irrigation volumes, respectively. PRDSDI significantly decreased the crude protein by 5.4% and 8.4% in 2018 with 10-mm and 20-mm irrigation volumes and relative feed value by 15.0% with 20-mm irrigation volume in 2017 and 9.8% with 10-mm irrigation volume in 2018, respectively. In addition, PRDSDI significantly increased the alfalfa average hay yield by 49.5% and 59.6% with 10-mm and 20-mm irrigation volumes in 2018, respectively. Our results provide a counterexample for PRDSDI to improve crop quality. Although there was no significant improvement in average quality yield by PRDSDI, the positive impact of average hay yield on quality yield outweighed the negative impact of quality content. Thus, it has the potential to improve quality yields. The novel findings regarding the effects of PRDSDI on quality yield are potentially favorable for the forage feed value in water-limited areas.

Recombinant L. lactis vaccine LL-plSAM-WAE targeting four virulence factors provides mucosal immunity against H. pylori infection.

BACKGROUND: Helicobacter pylori (H. pylori) causes chronic gastric disease. An efficient oral vaccine would be mucosa-targeted and offer defense against colonization of invasive infection in the digestive system. Proteolytic enzymes and acidic environment in the gastrointestinal tract (GT) can, however, reduce the effectiveness of oral vaccinations. For the creation of an edible vaccine, L. lactis has been proposed as a means of delivering vaccine antigens. RESULTS: We developed a plSAM (pNZ8148-SAM) that expresses a multiepitope vaccine antigen SAM-WAE containing Urease, HpaA, HSP60, and NAP extracellularly (named LL-plSAM-WAE) to increase the efficacy of oral vaccinations. We then investigated the immunogenicity of LL-plSAM-WAE in Balb/c mice. Mice that received LL-plSAM-WAE or SAM-WAE with adjuvant showed increased levels of antibodies against H. pylori, including IgG and sIgA, and resulted in significant reductions in H. pylori colonization. Furthermore, we show that SAM-WAE and LL-plSAM-WAE improved the capacity to target the vaccine to M cells. CONCLUSIONS: These findings suggest that recombinant L. lactis could be a promising oral mucosa vaccination for preventing H. pylori infection.