Immunotherapy and delivery systems for melanoma.

Melanoma is a highly malignant tumor of melanocyte origin that is prone to early metastasis and has a very poor prognosis. Early melanoma treatment modalities are mainly surgical, and treatment strategies for advanced or metastatic melanoma contain chemotherapy, radiotherapy, targeted therapy and immunotherapy. The efficacy of chemotherapy and radiotherapy has been unsatisfactory due to low sensitivity and strong toxic side effects. And targeted therapy is prone to drug resistance, so its clinical application is limited. Melanoma has always been the leader of immunotherapy for solid tumors, and how to maximize the role of immunotherapy and how to implement immunotherapy more accurately are still urgent to be explored. This review summarizes the common immunotherapies and applications for melanoma, illustrates the current research status of melanoma immunotherapy delivery systems, and discusses the advantages and disadvantages of each delivery system and its prospects for clinical application.

LESA-Net: Semantic segmentation of multi-type road point clouds in complex agroforestry environment.

Point-cloud semantic segmentation is a visual task essential for agricultural robots to comprehend natural agroforestry environments. However, owing to the extremely large amount of point-cloud data in agroforestry environments, learning effective features for semantic segmentation from large-scale point clouds is challenging. Therefore, to address this issue and achieve accurate semantic segmentation of different types of road-surface point clouds in large-scale agroforestry environments, this study proposes a point-cloud semantic segmentation network framework based on double-distance self-attention. First, a point-cloud local feature enhancement module is proposed. This module primarily extends the receptive field and enhances the generalizability of multidimensional features by incorporating reflection intensity information and a spatial feature-encoding block that is enhanced with contextual semantic information. Second, we introduce a dual-distance attention pooling (DDAPS) block based on the self-attention mechanism. This block initially learns the feature representation of the local neighborhood of each point through the self-attention mechanism. Then, it uses the DDAPS block to aggregate more discriminative local neighborhood point features. Finally, extensive experimental results on large-scale point-cloud datasets, SemanticKITTI and RELLIS-3D, demonstrate that our algorithm outperforms similar algorithms in large-scale agroforestry environments.

Novel Quantitative Liver Steatosis Assessment Method With Ultrasound Harmonic Imaging.

OBJECTIVES: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent liver disorder in Western countries, with approximately 20%-30% of the MASLD patients progressing to severe stages. There is an urgent need for noninvasive, cost-effective, widely accessible, and precise biomarkers to evaluate liver steatosis. This study aims to assess and compare the diagnostic performance of a novel reference frequency method-based ultrasound attenuation coefficient estimation (ACE) in both fundamental (RFM-ACE-FI) and harmonic (RFM-ACE-HI) imaging for detecting and grading liver steatosis. METHODS: An Institutional Review Board-approved prospective study was carried out between December 2018 and October 2022. A total number of 130 subjects were enrolled in the study. The correlation between RFM-ACE-HI values and magnetic resonance imaging proton density fat fraction (MRI-PDFF), as well as between RFM-ACE-FI values and MRI-PDFF were calculated. The diagnostic performance of RFM-ACE-FI and RFM-ACE-HI was evaluated using receiver operating characteristic (ROC) curve analysis, as compared to MRI-PDFF. The reproducibility of RFM-ACE-HI was assessed by interobserver agreement between two sonographers. RESULTS: A strong correlation was observed between RFM-ACE-HI and MRI-PDFF, with R = 0.88 (95% confidence interval [CI]: 0.83-0.92; P < .001), while the correlation between RFM-ACE-FI and MRI-PDFF was R = 0.65 (95% CI: 0.50-0.76; P < .001). The area under the ROC (AUROC) curve for RFM-ACE-HI in staging liver steatosis grades of S ≥ 1 and S ≥ 2 was 0.97 (95% CI: 0.91-0.99; P < .001) and 0.98 (95% CI: 0.93-1.00; P < .001), respectively, and 0.76 (95% CI: 0.65-0.85) and 0.80 (95% CI: 0.70-0.88) for RFM-ACE-FI, respectively. Great reproducibility was achieved for RFM-ACE-HI, with an interobserver agreement of R = 0.97 (95% CI: 0.94-0.99; P < .001). CONCLUSIONS: The novel RFM-ACE-HI method offered high liver steatosis diagnostic accuracy and reproducibility, which has important clinical implications for early disease intervention and treatment evaluation.

Modulation of fecal microbiota and reductions in fecal antibiotic resistance genes (ARGs) driven by Weissella-fermented feed in growing pigs.

Probiotics-induced feed fermentation can improve the composition of microbiota, leading to benefits in pig production. However, the influence of probiotics-driven feed fermentation on pollution reduction is limited. This study aimed to analyze the impact of Weissella-based feed fermentation on the chemical characteristics, changes in microbial abundance, and antibiotic resistance genes (ARGs). Moreover, the possible mechanism and the association among them was also analyzed. First, pigs reared on fermented feed exhibited improved growth performance. The fermentation group showed a significant reduction in emissions of total phosphorus (TP), total carbon (TC), organic matter (OM), copper (Cu), and zinc (Zn) levels in feces compared to the control group. The fermentation group also showed a significant decrease in the ARGs, especially for the tetX, tetW, tetQ, tetL, tetO, tet32, tet44, ermG, ermF, CfxA2, CfxA3, aph3-III, aadA, and ant9-I, compared to the control group. The primary functional microbiota, characterized by increased levels of Bifidobacterium, Megasphaera, and Mitsuokella, and decreased levels of Methanosphaera, and Ruminiclostridium, displayed both negative and positive correlations with ARGs, TC, TP, OM, Cu, and Zn. Furthermore, a significant association was observed between the alterations in microbiota and ARGs and the lactic acid concentration in the fermented feed. The molecular docking results showed a good fit between lactate dehydrogenase and three antibiotics, particularly tetracycline. In conclusion, these results offer novel targets and strategies to address environmental pollutants associated with pig farming.

Advances and Challenges in Large-Area Perovskite Light-Emitting Diodes.

Metal halide perovskite light-emitting diodes (PeLEDs) have shown promise for high-definition displays and flat-panel lighting because of their wide color gamut, narrow emission band, and high brightness. The external quantum efficiency of PeLEDs increased rapidly from ≈1% to more than 25% in the past few years. However, most of these high-performance devices are fabricated using a spin coating method with a small device area of <0.1 cm2, limiting their commercial applications. Recently, large-area PeLEDs have attracted growing attention and significant breakthroughs have been reported. This perspective first introduces the pros and cons of each technique in making large-area PeLEDs. The advances in the fabrication of large-area PeLEDs are then summarized using spin coating and mass-production methods such as inkjet printing, blade coating, and thermal evaporation. Moreover, the challenging issues will be discussed that are urgent to be solved for large-area PeLEDs.

BCMA-BBZ-OX40 CAR-T Therapy Using an Instant Manufacturing Platform in Multiple Myeloma.

BACKGROUND: Chimeric antigen receptor (CAR)-T cell has revolutionary efficacy against relapsed/refractory multiple myeloma (R/R MM). However, current CAR-T cell therapy has several limitations including long vein-to-vein time and limited viability. METHODS: A 4-1BB-costimulated B-cell maturation antigen (BCMA) CAR-T integrating an independently-expressed OX40 (BCMA-BBZ-OX40) was designed and generated by a traditional manufacturing process (TraditionCART) or instant manufacturing platform (named InstanCART). The tumor-killing efficiency, differentiation, exhaustion, and expansion level were investigated in vitro and in tumor-bearing mice. An investigator-initiated clinical trial was performed in patients with R/R MM to evaluate the outcomes of both TraditionCART and InstanCART. The primary objective was safety within 1 month after CAR-T cell infusion. The secondary objective was the best overall response rate. RESULTS: Preclinical studies revealed that integrated OX40 conferred BCMA CAR-T cells with superior cytotoxicity and reduced exhaustion levels. InstanCART process further enhanced the proliferation and T-cell stemness of BCMA-BBZ-OX40 CAR-T cells. BCMA-BBZ-OX40 CAR-T cells were successfully administered in 22 patients with R/R MM, including 15 patients with TraditionCART and 7 patients with InstanCART. Up to 50% (11/22) patients had a high-risk cytogenetic profile and 36% (8/22) had extramedullary disease. CAR-T therapy caused grade 1-2 cytokine release syndrome in 19/22 (80%) patients, grade 1 neurotoxicity in 2/22 (9%) patients and led to ≥grade 3 adverse events including neutropenia (20/22, 91%), thrombocytopenia (15/22, 68%), anemia (12/22, 55%), creatinine increased (1/22, 5%), hepatic enzymes increased (5/22, 23%), and sepsis (1/22, 5%). The best overall response rate was 100%, and 64% (14/22) of the patients had a complete response or better. The median manufacturing time was shorter for InstanCART therapy (3 days) than for TraditionCART therapy (10 days). Expansion and duration were dramatically higher for InstanCART cells than for TraditionCART cells. CONCLUSIONS: BCMA-BBZ-OX40 CAR-T cells were well tolerated and exhibited potent responses in patients with R/R MM. InstanCART shortened the manufacturing period compared to TraditionCART, and improved the cellular kinetics. Our results demonstrated the potency and feasibility of OX40-modified BCMA CAR-T cells using InstanCART technology for R/R MM therapy. TRIAL REGISTRATION NUMBER: This trial was registered at www. CLINICALTRIALS: gov as #NCT04537442.

Silica nanoparticles cause ovarian dysfunction and fertility decrease in mice via oxidative stress-activated autophagy and apoptosis.

Silica nanoparticles (SiNPs) are widely used in various commercial applications, which inevitably increase the risk of human exposure. It's reported that SiNPs have toxic effects on fertility, however, the specific mechanism of female reproductive toxicity induced by SiNPs remains confusing. In this study, female C57BL/6 mice at the age of 8 weeks were administrated orally with SiNPs at doses of 0, 3, and 10 mg/kg bw. every day in the presence/absence of NAC for eight weeks. The results showed that SiNPs could cause damage to ovaries and reduce the number of ovarian follicles, which led to disruption of sex hormone, altered estrous cyclicity and decreased female fertility. In addition, SiNPs induced oxidative stress in the ovary, as manifested by increased ROS and MDA levels, decreased SOD activity and inhibition of the Nrf2/HO-1 signaling pathway. Further study revealed that exposure to SiNPs resulted in mitochondrial dysfunction and promoted autophagy mediated by PI3K/AKT/mTOR and PINK1/Parkin signaling pathways. Meanwhile, apoptosis is also involved in SiNPs-induced cell death in a cooperative and synchronized manner, as evidenced by an increase in apoptosis-positive cells and activation of the ATM/p53-mediated apoptotic pathway. The supplementation of NAC restored most of the reproductive characteristics of the mice to its physiological range. These results demonstrated that SiNPs could cause ovarian damage via inducing oxidative stress and mitochondrial dysfunction, which led to autophagy and apoptosis, and ultimately resulting in abnormal folliculogenesis and female subfertility.

Natural variations of maize ZmLecRK1 determine its interaction with ZmBAK1 and resistance patterns to multiple pathogens.

Maize (Zea mays L.) is one of the most important crops in the world, but its yield and quality are seriously affected by diverse diseases. Identifying broad-spectrum resistance genes is crucial for developing effective strategies to control the disease in maize. In a genome-wide study in maize, we identified a G-type lectin receptor kinase ZmLecRK1 as a new resistance protein against Pythium aphanidermatum, one of the causal pathogens of stalk rot in maize. Genetic analysis showed that the specific ZmLecRK1 allele can confer resistance to multiple pathogens in maize. The resistant variant of ZmLecRK1-mediated cell death and disease resistance require the co-receptor leucine-rich repeat kinase ZmBAK1. A naturally occurring A404S variant in the extracellular domain of ZmLecRK1 determines the ZmLecRK1-ZmBAK1 interaction and the formation of ZmLecRK1-related protein complexes. The amino acid S404, as found in the ZmLecRK1 susceptibility variant, constitutes the ancestral version and is conserved among the majority of grass species, while the resistance variant with A404 is only present in a few maize inbred lines. Substitution of S by A at position 404 in ZmLecRK1-like proteins of sorghum and rice greatly enhances their ability to induce cell death. We propose that selection for the ZmLecRK1 resistance variant enhances its binding affinity to the co-receptor ZmBAK1, thereby enhancing the formation of active complexes for defense. Finally, transcriptomic analysis suggests that ZmLecRK1 likely regulates gene expression related to pathways in cell wall organization or biogenesis in response to pathogen infection. Our work highlights the biotechnological potential for generating disease-resistant crops by precisely modulating the activity of ZmLecRK1 and its homologs through targeted base editing.

Proteus faecis: a potentially pathogenic bacterium isolated from the freshwater Yangtze finless porpoise.

Proteus faecis is a gram-negative facultative anaerobic rod-shaped bacterium capable of swarming motility. It has been isolated from numerous sources such as humans, animals, and refuse and is considered potentially pathogenic towards humans. In this study, bacteria were isolated from the blowhole of a Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis; YFP) living in captivity in China. One bacterium, P. faecis porpoise, was isolated and whole genome sequencing done. Biofilm formation, motility and antimicrobial resistance were also investigated. To find putative virulence factors, the genome of P. faecis strain porpoise was compared to the genomic sequences of eight other P. faecis isolates using the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) ( https://www.bv-brc.org/ ). The goal of this study was to initially characterize the pathogenicity of this bacterium isolated from a cetacean species using both pathogenomics and conventional approaches.

Fei-Yan-Qing-Hua decoction exerts an anti-inflammatory role during influenza by inhibiting the infiltration of macrophages and neutrophils through NF-κB and p38 MAPK pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Fei-Yan-Qing-Hua decoction (FYQHD) is an empirical formula that has shown clinical success in treating community-acquired pneumonia (CAP) for two decades. Influenza viral infection is a significant trigger for severe pneumonia, yet the role of FYQHD in treating influenza remains unclear. AIM OF THE STUDY: This study aimed to assess the potential efficacy of FYQHD in treating influenza viral infection and to elucidate its underlying mechanisms. MATERIALS AND METHODS: The protective effects of FYQHD against influenza were evaluated through survival assessments and pathological analyses. Transcriptomic analysis was performed to identify the genes and pathways influenced by FYQHD in influenza. The anti-inflammatory effects and molecular mechanisms of FYQHD were studied in macrophages stimulated by Toll-like receptor (TLR) 7 ligation in vitro. The key constituents of FYQHD absorbed in mouse sera were identified using untargeted metabolomics, and the anti-inflammatory activity of some of these compounds in macrophages was evaluated using ELISA. RESULTS: Our findings demonstrate that FYQHD enhances survival and reduces lung damage in PR8-infected mice, primarily through its anti-inflammatory properties. Lung indexes and organ damage were significantly lower in the PR8 + OSV + FYQHD group compared to the PR8 + OSV group, indicating a potential complementary therapeutic effect of FYQHD and OSV in treating influenza. FYQHD effectively reduced chemokine expression, thereby decreasing the chemotaxis and infiltration of inflammatory monocytes/macrophages and neutrophils in the lungs. The anti-inflammatory effects of FYQHD in macrophages were achieved through the inhibition of NF-κB activation and p38 phosphorylation. The key constituents of FYQHD absorbed in mouse sera were identified, with some, such as wogonin, luteolin, kaempferol, and isorhamnetin, showing anti-inflammatory effects in primary macrophages. CONCLUSION: FYQHD demonstrates protective efficacy against influenza and shows promise as an adjuvant therapeutic agent, particularly when used in combination with antiviral drugs like OSV. The potent anti-inflammatory components within FYQHD provide a basis for further exploration in drug research and development aimed at combating influenza.

m6A methyltransferase ZC3H13 improves pulmonary fibrosis in mice through regulating Bax expression.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease. N6-methyladenosine (m6A) is a reversible RNA modification that was shown to be associated with IPF development. The present study aimed to explore the function and potential mechanism of the m6A methylation enzyme zinc finger CCCH-type containing 13 (ZC3H13) in IPF. In the study, bioinformatic screening yielded a differentially expressed m6A gene, ZC3H13, which was down-regulated in GEO microarrays, BLM-induced mouse models, and cellular models. Overexpression of ZC3H13 reduced histopathological damage of lung tissues in mice, mitigated fibrosis (including reduced α-SMA, collagen Ⅰ, and Vimentin levels, and elevated E-cadherin levels), decreased lung/body weight ratio and lung hydroxyproline levels, reduced oxidative stress (increased SOD activity and GSH-Px activity and decreased MDA levels), suppressed apoptosis within lung tissues and MLE-12 cells, promoted Bcl-2 expression, and inhibited Bax expression. Bax expression was found to be negatively correlated with ZC3H13 expression by correlation analysis. ZC3H13 could bind Bax mRNA and promote its m6A methylation through reading protein YTHDC1, thereby inhibiting its stability. Bax inhibition ameliorated BLM-induced MLE-12 cell dysfunction and partially abrogated the inhibition of MLE-12 cell function by ZC3H13 downregulation. In conclusion, m6A methyltransferase ZC3H13 impedes lung epithelial cell apoptosis and thus improves pulmonary fibrosis by promoting Bax mRNA m6A methylation and down-regulating Bax expression through reading protein YTHDC1.

Evolution of the Correlated Genomic Variation Landscape Across a Divergence Continuum in the Genus Castanopsis.

The heterogeneous landscape of genomic variation has been well documented in population genomic studies. However, disentangling the intricate interplay of evolutionary forces influencing the genetic variation landscape over time remains challenging. In this study, we assembled a chromosome-level genome for Castanopsis eyrei and sequenced the whole genomes of 276 individuals from 12 Castanopsis species, spanning a broad divergence continuum. We found highly correlated genomic variation landscapes across these species. Furthermore, variations in genetic diversity and differentiation along the genome were strongly associated with recombination rates and gene density. These results suggest that long-term linked selection and conserved genomic features have contributed to the formation of a common genomic variation landscape. By examining how correlations between population summary statistics change throughout the species divergence continuum, we determined that background selection alone does not fully explain the observed patterns of genomic variation; the effects of recurrent selective sweeps must be considered. We further revealed that extensive gene flow has significantly influenced patterns of genomic variation in Castanopsis species. The estimated admixture proportion correlated positively with recombination rate and negatively with gene density, supporting a scenario of selection against gene flow. Additionally, putative introgression regions exhibited strong signals of positive selection, an enrichment of functional genes, and reduced genetic burdens, indicating that adaptive introgression has played a role in shaping the genomes of hybridizing species. This study provides insights into how different evolutionary forces have interacted in driving the evolution of the genomic variation landscape.

Novel Br-doped Bi2WO6 photocatalyst for high-efficiency removal of norfloxacin: mechanism and photocatalytic activity.

In this work, the bismuth tungstate (Bi2WO6) photocatalyst was successfully prepared, and the pure Bi2WO6 was modified with Br (Br-Bi2WO6). The effects of different experimental conditions on the degradation of norfloxacin (NOR) solution under visible light were investigated. The Br-Bi2WO6 photocatalyst was characterized by FTIR, XRD, SEM, BET, XPS, DRS, EIS, and EPR. The results show that the Br-modified Bi2WO6 photocatalyst can effectively improve the photocatalytic performance. The best photocatalytic performance of Br-Bi2WO6 was observed when the doping amount of Br was 3%. The degradation percentage of norfloxacin can reach 94.67%. The presence of anions and cations (Cl-, SO42-, Ag+, and Cu2+) in the solution significantly inhibited the photocatalytic activity of 3%Br-Bi2WO6. The photocatalytic degradation of norfloxacin by 3%Br-Bi2WO6 was not greatly affected in the presence of HCO3- and NO3-. The characterization analysis showed that Br was successfully doped on the Bi2WO6 photocatalyst, and the original structure of Bi2WO6 was not destroyed by the addition of Br. Br doping increased the specific surface area of Bi2WO6 and decreased the band gap of Bi2WO6 resulting in a broader visible light absorption range. In addition, Br doping promoted the migration rate of photogenerated electron-hole pairs. The ·O2- and h+ played a major role in the photodegradation of norfloxacin, and the mechanism of photocatalytic degradation of norfloxacin by Br-Bi2WO6 was proposed.

Primary cutaneous cribriform tumor: A case report and literature review.

In the updated 5th edition of the WHO Classification of Skin Tumors, primary cutaneous cribriform carcinoma has been renamed cribriform tumor. This entity is a rare sweat gland neoplasm with undetermined malignant potential, with only 46 cases reported to date. Herein, we present a case of a 30-year-old female with a solitary nodule in the left thigh subcutaneous tissue. Histopathological examination revealed a well-defined dermal nodule composed of monomorphic, deeply staining cells arranged in solid nests, tubular, and cribriform patterns, with no recurrence or distant metastasis observed during a 1-year follow-up. Summarizing all 47 cases, they exhibited consistent, reproducible histological morphology and similar immunohistochemistry. Although the tumor nests lacked myoepithelial cells peripherally, all cleanly excised cases showed no recurrence or distant metastasis, suggesting a benign biological behavior. We argue against overtreatment.

Population pharmacokinetics of long-term hydroxychloroquine therapy in patients with rheumatic diseases.

AIMS: Hydroxychloroquine (HCQ) is recommended for the long-term treatment of rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. Given the complex process of HCQ metabolism and individual physiological differences, the metabolic profile of HCQ after long-term administration is unknown. This study aimed to establish a population pharmacokinetic model for long-term HCQ treatment in patients with rheumatic diseases and to identify the factors influencing HCQ metabolism. METHODS: This study included 274 HCQ whole-blood trough concentration data points from 203 patients with rheumatic diseases, all of whom had taken HCQ for more than 6 months, with a median duration of 36 months. A nonlinear mixed-effects model was derived to establish a population pharmacokinetic model, and potential influencing factors were investigated. Different covariates were used to simulate the optimal dose. RESULTS: The final model describing the HCQ blood concentration-time profile was a compartmental model with first-order absorption. The estimated values for apparent clearance and volume of distribution were 16.4 L/h and 1220 L, respectively. The clearance of HCQ gradually increased with increasing dosing regimens and weight gain. Monte Carlo simulations were used to determine the optimal dosage regimens for patients with different body weights and drug durations. The simulation results revealed that an initial dose of 5 mg/kg was appropriate. CONCLUSIONS: We developed a population pharmacokinetic model for long-term HCQ therapy in patients with rheumatic diseases. HCQ clearance from whole blood increased progressively with increasing duration of drug administration.

Contributions of individual qSOFA elements to assessment of severity and for prediction of mortality.

BACKGROUND: The quick sequential [sepsis-related] organ failure assessment (qSOFA) acts as a prompt to consider possible sepsis. The contributions of individual qSOFA elements to assessment of severity and for prediction of mortality remain unknown. METHODS: A total of 3974 patients with community-acquired pneumonia were recruited to an observational prospective cohort study. The area under the receiver operating characteristic curve (AUROC), odds ratio, relative risk and Youden's index were employed to assess discrimination. RESULTS: Respiratory rate ≥22/min demonstrated the most superior diagnostic value, indicated by largest odds ratio, relative risk and AUROC, and maximum Youden's index for mortality. However, the indices for altered mentation and systolic blood pressure (SBP) ≤100 mm Hg decreased notably in turn. The predictive validities of respiratory rate ≥22/min, altered mentation and SBP ≤100 mm Hg were good, adequate and poor for mortality, indicated by AUROC (0.837, 0.734 and 0.671, respectively). Respiratory rate ≥22/min showed the strongest associations with SOFA scores, pneumonia severity index, hospital length of stay and costs. However, SBP ≤100 mm Hg was most weakly correlated with the indices. CONCLUSIONS: Respiratory rate ≥22/min made the greatest contribution to parsimonious qSOFA to assess severity and predict mortality. However, the contributions of altered mentation and SBP ≤100 mm Hg decreased strikingly in turn. It is the first known prospective evidence of the contributions of individual qSOFA elements to assessment of severity and for prediction of mortality, which might have implications for more accurate clinical triage decisions.

Respiratory rate ≥22/min demonstrated the most superior diagnostic value.Respiratory rate ≥22/min showed the strongest association with severity.Respiratory rate ≥22/min, altered mentation and SBP ≤100 mm Hg predicted mortality well, adequately and poorly, respectively.

A sucrose ferulate cycle linchpin for ferulyolation of arabinoxylans in plant commelinids.

A transformation in plant cell wall evolution marked the emergence of grasses, grains and related species that now cover much of the globe. Their tough, less digestible cell walls arose from a new pattern of cross-linking between arabinoxylan polymers with distinctive ferulic acid residues. Despite extensive study, the biochemical mechanism of ferulic acid incorporation into cell walls remains unknown. Here we show that ferulic acid is transferred to arabinoxylans via an unexpected sucrose derivative, 3,6-O-diferuloyl sucrose (2-feruloyl-O-α-D-glucopyranosyl-(1'→2)-3,6-O-feruloyl-ß-D-fructofuranoside), formed by a sucrose ferulate cycle. Sucrose gains ferulate units through sequential transfers from feruloyl-CoA, initially at the O-3 position of sucrose catalysed by a family of BAHD-type sucrose ferulic acid transferases (SFT1 to SFT4 in maize), then at the O-6 position by a feruloyl sucrose feruloyl transferase (FSFT), which creates 3,6-O-diferuloyl sucrose. An FSFT-deficient mutant of maize, disorganized wall 1 (dow1), sharply decreases cell wall arabinoxylan ferulic acid content, causes accumulation of 3-O-feruloyl sucrose (α-D-glucopyranosyl-(1'→2)-3-O-feruloyl-ß-D-fructofuranoside) and leads to the abortion of embryos with defective cell walls. In vivo, isotope-labelled ferulic acid residues are transferred from 3,6-O-diferuloyl sucrose onto cell wall arabinoxylans. This previously unrecognized sucrose ferulate cycle resolves a long-standing mystery surrounding the evolution of the distinctive cell wall characteristics of cereal grains, biofuel crops and related commelinid species; identifies an unexpected role for sucrose as a ferulate group carrier in cell wall biosynthesis; and reveals a new paradigm for modifying cell wall polymers through ferulic acid incorporation.

Perylene-Diimide-Based Supramolecular Radical Anion as a Platform for Highly Effective Photoreduction of Inert Sulfoxide to Sulfide.

Due to the limitations of common photoredox catalysts, unlocking their applications in photoreduction reactions remains an ongoing challenge. We herein present a supramolecular radical anion, PDI(CB[7])2, that formed by the assembly of perylene diimide derivative (PDI) and cucurbit[7]uril (CB[7]) via a host-guest interaction for an effective photoreduction reaction. Studies revealed that it could effectively accomplish a consecutive excitation process by two-photon excitation, enabling a potent photoreductant PDI(CB[7])2• - * that can even reduce the inert feedstocks, such as sulfoxides to sulfides. Mechanistic investigations indicate that, besides exceptional photophysical properties, supramolecular PDI(CB[7])2 also significantly enhances the lifetime and robustness of the in situ generated higher energy photoreductant PDI(CB[7])2• - * upon second quantum photon excitation, leading to the observed highly active photoreducing behavior.

Fed-batch fermentation strategy for efficient welan gum production by Sphingomonas sp. FM01.

BACKGROUND: As a novel type of extracellular polysaccharide produced by Sphingomonas sp., welan gum has been widely applied in various fields because of its excellent properties. The study has improved the fermentation process. RESULTS: The initial sucrose concentration, temperature and stirring speed were set to 20 g L-1, 33 °C and 400 rpm, respectively, and 13.3 g L-1 sucrose was added at 24, 40 and 56 h. The temperature and stirring speed were then set at 28 °C and 600 rpm from 24 to 48 h and 28 °C and 600 rpm from 48 to 72 h, respectively. As a result, welan gum production, dry cell weight, sucrose conversion rate and viscosity were correspondingly increased to 38.60 g L-1, 5.47 g L-1, 0.64 g g-1 and 3779 mPa·s, respectively. In addition, the mechanism by which fermentation strategy promotes welan gum synthesis was investigated by transcriptome analysis. CONCLUSION: Improving respiration and ATP supply, reducing unnecessary protein synthesis, and alleviating competition between cell growth and welan gum synthesis contribute to promoting the fermentation performance of Sphingomonas sp., thus providing a practical strategy for efficient welan gum production. © 2024 Society of Chemical Industry.

UFMylation is involved in serum inflammatory cytokines generation and splenic T cell activation induced by lipopolysaccharide.

UFMylation, a novel ubiquitin-like protein modification system, has been recently found to be activated in inflammation. However, the effects of UFMylation activation on inflammation in vivo remains unclear. In the present study, we generated a UFMylation activated mice using transgenic (TG) techniques. Lipopolysaccharide (LPS) was used to induce systemic inflammation in both TG and non-transgenic (NTG) mice. Serum cytokines were detected using a Mouse Cytokine Array, and the proportions of splenic NK, B and T cells were determined by using flow cytometry. We found that TG mice showed increased serum G-CSF, TNF RII and decreased serum TCA-3, CD30L, bFGF, IL-15 and MIG compared with NTG mice at baseline. Furthermore, serum cytokines in TG mice exhibited different responses to LPS compared to NTG mice. LPS up-regulated serum TNF RII, G-CSF, MCP-5, RANTES, KC, BLC, MIG and down-regulated IL-1b, IL-2, IL-3, IL-4, IL-5, IL-7, IL-10, IL-12p40, IL-15, IL-17, IFN-γ, TCA-3, Eotaxin-2, LIX, MCP-1, TNFα, GM-CSF in NTG mice, whereas LPS up-regulated G-CSF, MCP-5, RANTES, KC, BLC, MIG, ICAM-1, PF4, Eotaxin, CD30L, MIP-1a, TNFRI and down-regulated IL-1b, IL-3, LIX, MCP-1, TNFα, GM-CSF in TG mice. Data from flow cytometry indicated that LPS significantly reduced the percentages of NK and NKT cells in NTG mice, whereas UFMylation activation inhibited LPS-induced NKT cell decrease. The proportions of B cells, total CD4+ and total CD8+ T cells were comparable between TG and NTG mice in response to LPS treatment, whereas the percentages of CD4+CD69+ and CD8+CD69+T cells were lower in TG mice. These findings suggest that UFMylation may alter LPS-induced serum cytokine profile and participate in splenic T cell activation in vivo.