20(S)-ginsenoside Rh2 ameliorates ATRA resistance in APL by modulating lactylation-driven METTL3.

Background: 20(S)-ginsenoside Rh2(GRh2), an effective natural histone deacetylase inhibitor, can inhibit acute myeloid leukemia (AML) cell proliferation. Lactate regulated histone lactylation, which has different temporal dynamics from acetylation. However, whether the high level of lactylation modification that we first detected in acute promyelocytic leukemia (APL) is associated with all-trans retinoic acid (ATRA) resistance has not been reported. Furthermore, Whether GRh2 can regulate lactylation modification in ATRA-resistant APL remains unknown. Methods: Lactylation and METTL3 expression levels in ATRA-sensitive and ATRA-resistant APL cells were detected by Western blot analysis, qRT-PCR and CO-IP. Flow cytometry (FCM) and APL xenograft mouse models were used to determine the effect of METTL3 and GRh2 on ATRA-resistance. Results: Histone lactylation and METTL3 expression levels were considerably upregulated in ATRA-resistant APL cells. METTL3 was regulated by histone lactylation and direct lactylation modification. Overexpression of METTL3 promoted ATRA-resistance. GRh2 ameliorated ATRA-resistance by downregulated lactylation level and directly inhibiting METTL3. Conclusions: This study suggests that lactylation-modified METTL3 could provide a promising strategy for ameliorating ATRA-resistance in APL, and GRh2 could act as a potential lactylation-modified METTL3 inhibitor to ameliorate ATRA-resistance in APL.

Clinical phenotypes of adult-onset Behçet's syndrome: a comprehensive cross-sectional study in China.

Behçet's syndrome (BS) is a variant vasculitis that can involve multiple organs with inflammatory manifestations. This study aimed to provide a more comprehensive analysis of the clinical phenotypes and characteristics of BS patients. We enrolled 2792 BS patients referred from China nationwide to Huadong Hospital Affiliated to Fudan University from October 2012 to December 2022. Detailed assessments of demographic information, clinical manifestations, laboratory results, gastroscopy, and medical imaging were conducted. Cluster analysis was performed based on 13 variables to determine the clinical phenotypes, and each phenotype was characterized according to the features of BS patients. A total of 1834 BS patients were included, while 958 invalid patients were excluded. The median age at onset was 31 years (IQR, 24-40 years), and the median disease duration was 10 years (IQR, 5-15 years). Eight clusters were identified, including mucocutaneous (n = 655, 35.7%), gastrointestinal (n = 363, 19.8%), articular (n = 184, 10%), ocular (n = 223, 12.2%), cardiovascular (n = 119, 6.5%), neurological (n = 118, 6.4%), vascular (n = 114, 6.2%), and hematological phenotype (n = 58, 3.2%). Ocular (RR = 1.672 (95% CI, 1.327-2.106); P < 0.001), gastrointestinal (RR = = 1.194 (95% CI, 1.031-1.383); P = 0.018), cardiovascular (RR = = 2.582 (95% CI, 1.842-3.620); P < 0.001), and vascular (RR = = 2.288 (95% CI, 1.600-3.272); P < 0.001) involvement were more prevalent in male BS patients, while the hematological (RR = 0.528 (95% CI, 0.360-0.776); P = 0.001) involvement was more common among female patients. BS presents significant heterogeneity and gender differences. The eight phenotypes of BS patients we propose hold the potential to assist clinicians in devising more personalized treatment and follow-up strategies. Key Points • This cluster analysis divided adult-onset BS into eight clinical phenotypes. • BS demonstrates a high level of clinical heterogeneity and gender differences. • Hematologic phenotypes of BS present distinctive clinical characteristics.

Maternal smoking, consumption of alcohol, and caffeinated beverages during pregnancy and the risk of childhood brain tumors: a meta-analysis of observational studies.

BACKGROUND: We conducted this meta-analysis to investigate the potential association between maternal smoking, alcohol and caffeinated beverages consumption during pregnancy and the risk of childhood brain tumors (CBTs). METHODS: A thorough search was carried out on PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Internet to identify pertinent articles. Fixed or random effects model was applied to meta-analyze the data. RESULTS: The results suggested a borderline statistically significant increased risk of CBTs associated with maternal smoking during pregnancy (OR 1.04, 95% CI 0.99-1.09). We found that passive smoking (OR 1.12, 95% CI 1.03-1.20), rather than active smoking (OR 1.00, 95% CI 0.93-1.07), led to an increased risk of CBTs. The results suggested a higher risk in 0-1 year old children (OR 1.21, 95% CI 0.94-1.56), followed by 0-4 years old children (OR 1.12, 95% CI 0.97-1.28) and 5-9 years old children (OR 1.11, 95% CI 0.95-1.29). This meta-analysis found no significant association between maternal alcohol consumption during pregnancy and CBTs risk (OR 1.00, 95% CI 0.80-1.24). An increased risk of CBTs was found to be associated with maternal consumption of caffeinated beverages (OR 1.16, 95% CI 1.07-1.26) during pregnancy, especially coffee (OR 1.18, 95% CI 1.00-1.38). CONCLUSIONS: Maternal passive smoking, consumption of caffeinated beverages during pregnancy should be considered as risk factors for CBTs, especially glioma. More prospective cohort studies are warranted to provide a higher level of evidence.

Potential therapeutic strategies to halt viral neuroinvasion.

The viral infection of the central nervous system is a significant public health concern. So far, most clinical cases of viral neuroinvasion are dealt with supportive and/or symptomatic treatments due to the unavailability of specific treatments. Thus, developing specific therapies is required to alleviate neurological symptoms and disorders. In this review, we shed light on molecular aspects of viruses' entry into the brain which upon targeting with specific drugs have shown promising efficacy in vitro and in preclinical in vivo model systems. Further assessing the therapeutic potential of these drugs in clinical trials may offer opportunities to halt viral neuroinvasion in humans.

Plant polysaccharide-derived edible film packaging for instant food: Rapid dissolution in hot water coupled with exceptional mechanical and barrier characteristics.

A comprehensive multiscale analysis was conducted to explore the effects of different ratios of these materials on its properties. The results show that KC played a crucial role in controlling solution viscosity and gel and sol temperatures. The dissolution time at high water temperatures primarily decreased with an increase in SA content. Higher KC and CS content increased tensile strength (TS) and elongation at break (ε), while also exhibiting better thermal stability. Water vapor transmission (WVT) and permeability (PV) initially decreased, then increased with the increase of SA and CS contents. Finally, an SA:KC:CS ratio of 1:3:2 showed optimal comprehensive properties, with a dissolution time of about 60.0 ± 3.8 s, TS of 23.80 ± 0.29 MPa, ε of 18.61 ± 0.34 %, WVT of 21.74 ± 0.62 g/m2·24h, and PV of 5.39 ± 0.17 meq/kg. Meanwhile, the SA:KC:CS edible food packaging only introduced minimal effects on food after dissolution, and the total bacterial count met regulatory standards.

HSD17B13 liquid-liquid phase separation promotes leukocyte adhesion in chronic liver inflammation.

The rs72613567:TA polymorphism in 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13) has been found to reduce the progression from steatosis to nonalcoholic steatohepatitis. In this study, we sought to define the pathogenic role of HSD17B13 in triggering liver inflammation. Here we find that HSD17B13 forms liquid-liquid phase separation (LLPS) around lipid droplets in the livers of nonalcoholic steatohepatitis patients. The dimerization of HSD17B13 supports the LLPS formation and promotes its enzymatic function. HSD17B13 LLPS increases the biosynthesis of platelet activating factor (PAF), which in turn promotes fibrinogen synthesis and leukocyte adhesion. Blockade of PAFR or STAT3 pathway inhibited the fibrinogen synthesis and leukocyte adhesion. Importantly, adeno-associated viral-mediated xeno-expression of human HSD17B13 exacerbated western diet/carbon tetrachloride-induced liver inflammation in Hsd17b13-/- mice. In conclusion, our results suggest that HSD17B13 LLPS triggers liver inflammation by promoting PAF-mediated leukocyte adhesion, and targeting HSD17B13 phase transition could be a promising therapeutic approach for treating hepatic inflammation in chronic liver disease.

International Myeloma Working Group immunotherapy committee consensus guidelines and recommendations for optimal use of T-cell-engaging bispecific antibodies in multiple myeloma.

Multiple myeloma remains an incurable disease, despite the development of numerous drug classes and combinations that have contributed to improved overall survival. Immunotherapies directed against cancer cell-surface antigens, such as chimeric antigen receptor (CAR) T-cell therapy and T-cell-redirecting bispecific antibodies, have recently received regulatory approvals and shown unprecedented efficacy. However, these immunotherapies have unique mechanisms of action and toxicities that are different to previous treatments for myeloma, so experiences from clinical trials and early access programmes are essential for providing specific recommendations for management of patients, especially as these agents become available across many parts of the world. Here, we provide expert consensus clinical practice guidelines for the use of bispecific antibodies for the treatment of myeloma. The International Myeloma Working Group is also involved in the collection of prospective real-time data of patients treated with such immunotherapies, with the aim of learning continuously and adapting clinical practices to optimise the management of patients receiving immunotherapies.

Advancing Neurological Health: Insights into Aging, Immunity, and Vascular Dynamics.

This editorial provides an overview of recent advancements in the understanding and treatment of neurological disorders, focusing on aging, immunity, and blood flow, as featured in this special issue. The first section explores the importance of identifying biomarkers of aging and aging-related diseases, such as Alzheimer's Disease, highlighting the emerging role of saliva-based biomarkers and the gut-brain axis in disease diagnosis and management. In the subsequent section, the dysregulated immune systems associated with aging are discussed, emphasizing the intricate landscape of the immune system during aging and its bidirectional relationship with neuroinflammation. Additionally, insights into the involvement of Myeloid-Derived Suppressor Cells (MDSCs) in Multiple Sclerosis (MS) pathogenesis are presented. The third section examines the role of microglia in neuroinflammation and various neurological diseases, including age-related macular degeneration (AMD) and Tuberculous Meningitis (TBM). Furthermore, the therapeutic potential of stem cell and extracellular vesicle-based therapies for stroke is explored, along with molecular mechanism of how inflammation regulates cerebral and myocardial ischemia. Finally, the importance of blood flow in maintaining vascular health and its impact on neurological disorders are discussed, highlighting the potential of novel assessment methods for optimizing patient care. Overall, this special issue offers valuable insights into the complex mechanisms underlying neurological disorders and identifies potential avenues for therapeutic intervention.

Japanese encephalitis virus NS1 and NS1' protein disrupts the blood-brain barrier through macrophage migration inhibitory factor-mediated autophagy.

Flaviviruses in the Japanese encephalitis virus (JEV) serogroup, such as JEV, West Nile virus, and St. Louis encephalitis virus, can cause severe neurological diseases. The nonstructural protein 1 (NS1) is a multifunctional protein of flavivirus that can be secreted by infected cells and circulate in the host bloodstream. NS1' is an additional form of NS1 protein with 52 amino acids extension at its carboxy-terminal and is produced exclusively by flaviviruses in the JEV serogroup. In this study, we demonstrated that the secreted form of both NS1 and NS1' can disrupt the blood-brain barrier (BBB) of mice, with NS1' exhibiting a stronger effect. Using the in vitro BBB model, we found that treatment of soluble recombinant JEV NS1 or NS1' protein increases the permeability of human brain microvascular endothelial cells (hBMECs) and leads to the degradation of tight junction proteins through the autophagy-lysosomal pathway. Consistently, NS1' protein exhibited a more pronounced effect compared to NS1 in these cellular processes. Further research revealed that the increased expression of macrophage migration inhibitory factor (MIF) is responsible for triggering autophagy after NS1 or NS1' treatment in hBMECs. In addition, TLR4 and NF-κB signaling was found to be involved in the activation of MIF transcription. Moreover, administering the MIF inhibitor has been shown to decrease viral loads and mitigate inflammation in the brains of mice infected with JEV. This research offers a novel perspective on the pathogenesis of JEV. In addition, the stronger effect of NS1' on disrupting the BBB compared to NS1 enhances our understanding of the mechanism by which flaviviruses in the JEV serogroup exhibit neurotropism.IMPORTANCEJapanese encephalitis (JE) is a significant viral encephalitis worldwide, caused by the JE virus (JEV). In some patients, the virus cannot be cleared in time, leading to the breach of the blood-brain barrier (BBB) and invasion of the central nervous system. This invasion may result in cognitive impairment, behavioral disturbances, and even death in both humans and animals. However, the mechanism by which JEV crosses the BBB remains unclear. Previous studies have shown that the flavivirus NS1 protein plays an important role in causing endothelial dysfunction. The NS1' protein is an elongated form of NS1 protein that is particularly produced by flaviviruses in the JEV serogroup. This study revealed that both the secreted NS1 and NS1' of JEV can disrupt the BBB by breaking down tight junction proteins through the autophagy-lysosomal pathway, and NS1' is found to have a stronger effect compared to NS1 in this process. In addition, JEV NS1 and NS1' can stimulate the expression of MIF, which triggers autophagy via the ERK signaling pathway, leading to damage to BBB. Our findings reveal a new function of JEV NS1 and NS1' in the disruption of BBB, thereby providing the potential therapeutic target for JE.

PLK1-activating IFI16-STING-TBK1 pathway induces apoptosis of intestinal epithelial cells in patients with intestinal Behçet's syndrome.

Inflammatory signals from immunological cells may cause damage to intestinal epithelial cells (IECs), resulting in intestinal inflammation and tissue impairment. Interferon-γ-inducible protein 16 (IFI16) was reported to be involved in the pathogenesis of Behçet's syndrome (BS). This study aimed to investigate how inflammatory cytokines released by immunological cells and IFI16 participate in the pathogenesis of intestinal BS. RNA sequencing and real-time quantitative PCR (qPCR) showed that the positive regulation of tumor necrosis factor-α (TNF-α) production in peripheral blood mononuclear cells (PBMCs) of intestinal BS patients may be related to the upregulation of polo like kinase 1 (PLK1) in PBMCs (P = 0.012). The plasma TNF-α protein level in intestinal BS was significantly higher than in healthy controls (HCs; P = 0.009). PBMCs of intestinal BS patients and HCs were co-cultured with human normal IECs (NCM460) to explore the interaction between immunological cells and IECs. Using IFI16 knockdown, PBMC-NCM460 co-culture, TNF-α neutralizing monoclonal antibody (mAb), stimulator of interferon genes (STING) agonist 2'3'-cGAMP, and the PLK1 inhibitor SBE 13 HCL, we found that PLK1 promotes the secretion of TNF-α from PBMCs of intestinal BS patients, which causes overexpression of IFI16 and induces apoptosis of IECs via the STING-TBK1 pathway. The expressions of IFI16, TNF-α, cleaved caspase 3, phosphorylated STING (pSTING) and phosphorylated tank binding kinase 1 (pTBK1) in the intestinal ulcer tissue of BS patients were significantly higher than that of HCs (all P < 0.05). PLK1 in PBMCs of intestinal BS patients increased TNF-α secretion, inducing IEC apoptosis via activation of the IFI16-STING-TBK1 pathway. PLK1 and the IFI16-STING-TBK1 pathway may be new therapeutic targets for intestinal BS.

Analysis of endophytic bacterial diversity in seeds of different genotypes of cotton and the suppression of Verticillium wilt pathogen infection by a synthetic microbial community.

BACKGROUND: In agricultural production, fungal diseases significantly impact the yield and quality of cotton (Gossypium spp.) with Verticillium wilt posing a particularly severe threat. RESULTS: This study is focused on investigating the effectiveness of endophytic microbial communities present in the seeds of disease-resistant cotton genotypes in the control of cotton Verticillium wilt. The technique of 16S ribosomal RNA (16S rRNA) amplicon sequencing identified a significant enrichment of the Bacillus genus in the resistant genotype Xinluzao 78, which differed from the endophytic bacterial community structure in the susceptible genotype Xinluzao 63. Specific enriched strains were isolated and screened from the seeds of Xinluzao 78 to further explore the biological functions of seed endophytes. A synthetic microbial community (SynCom) was constructed using the broken-rod model, and seeds of the susceptible genotype Xinluzao 63 in this community that had been soaked with the SynCom were found to significantly control the occurrence of Verticillium wilt and regulate the growth of cotton plants. Antibiotic screening techniques were used to preliminarily identify the colonization of strains in the community. These techniques revealed that the strains can colonize plant tissues and occupy ecological niches in cotton tissues through a priority effect, which prevents infection by pathogens. CONCLUSION: This study highlights the key role of seed endophytes in driving plant disease defense and provides a theoretical basis for the future application of SynComs in agriculture.

Targeting PRAME for acute myeloid leukemia therapy.

Despite significant progress in targeted therapy for acute myeloid leukemia (AML), clinical outcomes are disappointing for elderly patients, patients with less fit disease characteristics, and patients with adverse disease risk characteristics. Over the past 10 years, adaptive T-cell immunotherapy has been recognized as a strategy for treating various malignant tumors. However, it has faced significant challenges in AML, primarily because myeloid blasts do not contain unique surface antigens. The preferentially expressed antigen in melanoma (PRAME), a cancer-testis antigen, is abnormally expressed in AML and does not exist in normal hematopoietic cells. Accumulating evidence has demonstrated that PRAME is a useful target for treating AML. This paper reviews the structure and function of PRAME, its effects on normal cells and AML blasts, its implications in prognosis and follow-up, and its use in antigen-specific immunotherapy for AML.

Sertoli cells require hnRNPC to surport normal spermatogenesis and male fertility in mice.

Sertoli cells (SCs) act as highly polarized testicular cells that nutritionally support multiple stages of germ cell development. However, the gene regulation network in SCs for modulating germ cell development has yet to be fully understood. In this study, we report that heterogeneous nuclear ribonucleoproteins C (hnRNPC) in SCs are essential for germ cell development and male fertility. Conditional knockout of hnRNPC in mouse SCs leads to aberrant SC proliferation, disrupted cytoskeleton of SCs, and compromised blood-testis barrier function, resulting in loss of supportive cell function and, ultimately, defective spermiogenesis in mice. Further RNA-seq analyses revealed these phenotypes are likely caused by the dysregulated genes in hnRNPC-deficient SCs related to cell adhesion, cell proliferation, and apoptotic process. In conclusion, this study demonstrates that hnRNPC plays a critical role in SCs for maintaining the function of SCs and sustaining steady-state spermatogenesis in mice.

Integrative proteomic and transcriptomic analysis in the female goat ovary to explore the onset of puberty.

Puberty is considered a prerequisite for affecting reproductive performance and productivity. Little was known about molecular changes in pubertal goat ovaries. Therefore, we measured and performed a correlation analysis of the mRNA and proteins changes in the pre-pubertal and pubertal goat ovaries. The results showed that only six differentially expressed genes and differentially abundant proteins out of 18,139 genes and 7550 proteins quantified had significant correlations. CNTN2 and THBS1, discovered in the mRNA-mRNA interaction network, probably participated in pubertal and reproductive regulation by influencing GnRH receptor signals, follicular development, and ovulation. The predicted core transcription factors may either promote or inhibit the expression of reproductive genes and act synergistically to maintain normal reproductive function in animals. The interaction between PKM and TIMP3 with other proteins may impact animal puberty through energy metabolism and ovarian hormone secretion. Pathway enrichment analyses revealed that the co-associated key pathways between ovarian genes and proteins at puberty included calcium signalling pathway and olfactory transduction. These pathways were associated with gonadotropin-releasing hormone synthesis and secretion, signal transmission, and cell proliferation. In summary, these results enriched the potential molecules and signalling pathways that affect puberty and provided new insights for regulating and promoting the onset of puberty. SIGNIFICANCE: This study conducted the first transcriptomic and proteomic correlation analysis of pre-pubertal and pubertal goat ovaries and identified six significantly correlated molecules at both the gene and protein levels. Meanwhile, we were drawn to several molecules and signalling pathways that may play a regulatory role in the onset of puberty and reproduction by influencing reproductive-related gene expression, GnRH receptor signals, energy metabolism, ovarian hormone secretion, follicular development, and ovulation. This information contributed to identify potential biomarkers in pubertal goat ovaries, which was vital for predicting the onset of puberty and improving livestock performance.

Comparison of conventional DWI and intravoxel incoherent motion in differentiating between chromophobe renal cell carcinoma and renal oncocytoma: a preliminary study.

OBJECTIVE: Quantitative comparison of the diagnostic efficacy of conventional diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) in differentiating between chromophobe renal cell carcinoma(ChRCC) from renal oncocytoma(RO). METHODS: A total of 48 patients with renal tumors who had undergone DWI and IVIM were divided into two groups-ChRCC (n = 28) and RO (n = 20) groups, and the apparent diffusion coefficient (ADC), true diffusivity (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) and their diagnostic efficacy were compared between the two groups. RESULTS: The D* values were higher in the ChRCCs group compared to the RO groups (0.019 ± 0.003mm2/s vs.0.008 ± 0.002 mm2/s, p < 0.05). Moreover, the ADC, D and f values were higher in ROs compared to ChRCCs (0.61 ± 0.08 × 10-3mm2/s vs. 0.51 ± 0.06 × 10-3mm2/s, 1.02 ± 0.15 × 10-3mm2/s vs. 0.86 ± 0.07 × 10-3mm2/s, 0.41 ± 0.05 vs. 0.28 ± 0.02, p < 0.05). The areas of the ADC, D, D* and f values under the ROC curves in differentiating ChRCCs from ROs were 0.713, 0.839, 0.856 and 0.906, respectively. The cut-off values of ADC, D, D* and f were 0.54, 0.91, 0.013 and 0.31, respectively. The AUC, sensitivity, specificity and accuracy of the f values were 0.906, 89.3%, 80.0% and 89.6%, respectively. For pairwise comparisons of ROC curves and diagnostic efficacy, IVIM parameters, ie, D, D*and f offered better diagnostic accuracy than ADC in differentiating ChRCCs from ROs(p = 0.013, 0.016 and 0.008) with f having the highest diagnostic accuracy. CONCLUSION: IVIM parameters presented better performance than ADC in differentiating ChRCCs from ROs.

IL-12p40 deletion reduces M1 macrophage polarization and alleviates cardiac remodeling via regulating Th17 cells differentiation, but not γδT 17 cells, in TAC mice.

BACKGROUND: The interleukin (IL) -12 p40 subunit is the common subunit of IL-12 and IL-23. It affects the immune inflammatory response, which may be closely related to cardiac remodeling. In this study, the regulatory effect of IL-12p40 knockout (KO) on cardiac remodeling was investigated, and the underlying mechanism was explored. METHODS AND RESULTS: Mice were subjected to transverse aortic constriction (TAC) to establish a model of cardiac remodeling. First, IL-12p40 was deleted to observe its effects on cardiac remodeling and cardiac inflammation, and the results showed that IL-12p40 deletion reduced both T helper 17 (Th17) and γδT17 cell differentiation, decreased proinflammatory macrophage differentiation, alleviated cardiac remodeling, and relieved cardiac dysfunction in TAC mice. Next, we explored whether IL-17 regulated TAC-induced cardiac remodeling, and the results showed that IL-17 neutralization alleviated proinflammatory macrophage differentiation and cardiac remodeling in IL-12p40 knockout mice and WT mice. Neutralization with cluster of differentiation 4 receptor (CD4) and γδ T-cell receptor (γδTCR) antibodies inhibited pro-inflammatory macrophage polarization and improved cardiac remodeling, and CD4 neutralizing antibody (NAb) had more significant effects. Finally, adoptive transfer of Th17 cells aggravated proinflammatory macrophage differentiation and cardiac remodeling in TAC-treated CD4 KO mice, while neutralization with the IL-12p40 antibody alleviated these pathological changes. CONCLUSION: Mainly Th17 cells but not γδT17 cells secrete IL-17, which mediates IL-12p40, promotes the polarization of proinflammatory macrophages, and exacerbates cardiac remodeling in TAC mice. IL-12p40 may be a potential target for the prevention and treatment of cardiac remodeling.

Changes in physiology, antioxidant system, and gene expression in Microcystis aeruginosa under fenoxaprop-p-ethyl stress.

Fenoxaprop-p-ethyl (FE) is one of the typical aryloxyphenoxypropionate herbicides. FE has been widely applied in agriculture in recent years. Human health and aquatic ecosystems are threatened by the cyanobacteria blooms caused by Microcystis aeruginosa, which is one of the most common cyanobacteria responsible for freshwater blooming. Few studies have been reported on the physiological effects of FE on M. aeruginosa. This study analyzed the growth curves, the contents of chlorophyll a and protein, the oxidative stress, and the microcystin-LR (MC-LR) levels of M. aeruginosa exposed to various FE concentrations (i.e., 0, 0.5, 1, 2, and 5 mg/L). FE was observed to stimulate the cell density, chlorophyll a content, and protein content of M. aeruginosa at 0.5- and 1-mg/L FE concentrations but inhibit them at 2 and 5 mg/L FE concentrations. The superoxide dismutase and catalase activities were enhanced and the malondialdehyde concentration was increased by FE. The intracellular (intra-) and extracellular (extra-) MC-LR contents were also affected by FE. The expression levels of photosynthesis-related genes psbD1, psaB, and rbcL varied in response to FE exposure. Moreover, the expressions of microcystin synthase-related genes mcyA and mcyD and microcystin transportation-related gene mcyH were significantly inhibited by the treatment with 2 and 5 mg/L FE concentrations. These results might be helpful in evaluating the ecotoxicity of FE and guiding the rational application of herbicides in modern agriculture.

Preparation, antibacterial activity, and structure-activity relationship of low molecular weight κ-carrageenan.

κ-Carrageenan (KC) is a polysaccharide widely used in food industry. It has been widely studied for its excellent physicochemical and beneficial properties. However, the high molecular weight and high viscosity of KC make it difficult to be absorbed and to exert its' biological activities, thus limit its extensive industrial application. In order to solve this problem, five low molecular weight κ-carrageenans (DCPs) were prepared by the degradation of KC using hydrogen peroxide (H2O2) and ascorbic acid (AH2). The chemical compositions and structure characteristics of the DCPs were then determined. The results showed that H2O2 and AH2 could effectively degrade KC to DCPs, and DCPs remained the basic skeletal structure of KC. DCPs showed good antibacterial activities against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis. The Minimum Inhibitory Concentration (MIC) of DCPs with the highest antibacterial effects were 5.25, 4.5, 5.25, and 4.5 mg/mL, respectively. This is due to the underlying mechanism of DCPs that bind to the bacterial membrane proteins and change the membrane permeability, thus exerting antibacterial activity. In addition, Spearman's rank correlation and Ridge regression analysis revealed that the molecular weight and the contents of 3,6-anhydro-D-galactose, aldehyde group, carboxyl, and sulfate were the main structural characteristics affecting the antibacterial activity. Our findings reveal that the H2O2-AH2 degradation treatment could significantly improve the antibacterial activity of KC and provide insights into the quantitative structure-activity relationships of the antibacterial activity of DCPs.