Ecotoxicity of Cadmium along the Soil-Cotton Plant-Cotton Bollworm System: Biotransfer, Trophic Accumulation, Plant Growth, Induction of Insect Detoxification Enzymes, and Immunocompetence.

Cadmium (Cd) is a hazardous element that may jeopardize environmental safety and human health through biotransfer and trophic accumulation. Here, we tested Cd toxicity on cotton plants, cotton bollworms, and their responses. Results demonstrated that Cd accumulated in plant roots, aerial parts, insect larvae, pupae, and frass in a dose-dependent pattern. The ∼9.35 mg kg-1 of Cd in plant aerial parts, ∼3.68 in larvae, ∼6.43 in pupae, and high transfer coefficient (∼5.59) indicate significant mobility. The ∼19.61 mg kg-1 of Cd in larvae frass suggests an effective detoxification strategy, while BAFcotton (∼1.14) and BAFworm (∼0.54) indicated low bioaccumulation. Cadmium exposure resulted in compromised plant growth and yield as well as alterations in photosynthetic pigment contents, antioxidant enzyme activities, and certain life history traits of cotton bollworms. Furthermore, carboxylesterase activity and encapsulation rates of insect larvae decreased with increasing Cd concentrations, whereas acetylcholinesterase, phenol oxidase, glutathione S-transferase, and multifunctional oxidase exhibited hormesis responses.

Chrysomycins, Anti-Tuberculosis C-Glycoside Polyketides from Streptomyces sp. MS751.

A new dimeric C-glycoside polyketide chrysomycin F (1), along with four new monomeric compounds, chrysomycins G (2), H (3), I (4), J (5), as well as three known analogues, chrysomycins A (6), B (7), and C (8), were isolated and characterised from a strain of Streptomyces sp. obtained from a sediment sample collected from the South China Sea. Their structures were determined by detailed spectroscopic analysis. Chrysomycin F contains two diastereomers, whose structures were further elucidated by a biomimetic [2 + 2] photodimerisation of chrysomycin A. Chrysomycins B and C showed potent anti-tuberculosis activity against both wild-type Mycobacterium tuberculosis and a number of clinically isolated MDR M. tuberculosis strains.

High-yield porphyrin production through metabolic engineering and biocatalysis.

Porphyrins and their derivatives find extensive applications in medicine, food, energy and materials. In this study, we produced porphyrin compounds by combining Rhodobacter sphaeroides as an efficient cell factory with enzymatic catalysis. Genome-wide CRISPRi-based screening in R. sphaeroides identifies hemN as a target for improved coproporphyrin III (CPIII) production, and exploiting phosphorylation of PrrA further improves the production of bioactive CPIII to 16.5 g L-1 by fed-batch fermentation. Subsequent screening and engineering high-activity metal chelatases and coproheme decarboxylase results in the synthesis of various metalloporphyrins, including heme and the anti-tumor agent zincphyrin. After pilot-scale fermentation (200 L) and setting up the purification process for CPIII (purity >95%), we scaled up the production of heme and zincphyrin through enzymatic catalysis in a 5-L bioreactor, with CPIII achieving respective enzyme conversion rates of 63% and 98% and yielding 10.8 g L-1 and 21.3 g L-1, respectively. Our strategy offers a solution for high-yield bioproduction of heme and other valuable porphyrins with substantial industrial and medical applications.

New N-acylated aminoalkanoic acids from tea roots derived biocontrol agent Clonostachys rosea 15020.

Four new N-acylated aminoalkanoic acids, namely clonoroseins E-H (1-4), together with three previously identified analogs, clonoroseins A, B, and D (5-7), were identified from the endophytic fungus Clonostachys rosea strain 15020 (CR15020), using Feature-based Molecular Networking (FBMN). The elucidation of their chemical structures, including their absolute configurations, was achieved through spectroscopic analysis combined with quantum chemical calculations. Bioinformatics analyses suggested that an iterative type I HR-PKS (CrsE) generates the polyketide side chain of these clonoroseins. Furthermore, a downstream adenylate-forming enzyme of the PKS (CrsD) was suspected to function as an amide synthetase. CrsD potentially facilitates the transformation of the polyketide moiety into an acyl-AMP intermediate, followed by nucleophilic substitution with either ß-alanine or γ-aminobutyric acid to produce amide derivatives. These findings significantly expand our understanding of PKS-related products originating from C. rosea and also underscore the powerful application of FBMN analytical methods in characterization of new compounds.

Dynamic graph transformer network via dual-view connectivity for autism spectrum disorder identification.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that requires objective and accurate identification methods for effective early intervention. Previous population-based methods via functional connectivity (FC) analysis ignore the differences between positive and negative FCs, which provide the potential information complementarity. And they also require additional information to construct a pre-defined graph. Meanwhile, two challenging demand attentions are the imbalance of performance caused by the class distribution and the inherent heterogeneity of multi-site data. In this paper, we propose a novel dynamic graph Transformer network based on dual-view connectivity for ASD Identification. It is based on the Autoencoders, which regard the input feature as individual feature and without any inductive bias. First, a dual-view feature extractor is designed to extract individual and complementary information from positive and negative connectivity. Then Graph Transformer network is innovated with a hot plugging K-Nearest Neighbor (KNN) algorithm module which constructs a dynamic population graph without any additional information. Additionally, we introduce the PolyLoss function and the Vrex method to address the class imbalance and improve the model's generalizability. The evaluation experiment on 1102 subjects from the ABIDE I dataset demonstrates our method can achieve superior performance over several state-of-the-art methods and satisfying generalizability for ASD identification.

Transporters and phytohormones analysis reveals differential regulation of ryegrass (Lolium perenne L.) in response to cadmium and arsenic stresses.

Cadmium (Cd) and arsenic (As) are two highly toxic heavy metals and metalloids that coexist in many situations posing severe threats to plants. Our investigation was conducted to explore the different regulatory mechanisms of ryegrass (Lolium perenne L.) responding to individual and combined Cd and As stresses in hydroponics. Results showed that the ryegrass well-growth phenotype was not affected by Cd stress of 10 mg·L-1. However, As of 10 mg·L-1 caused rapid water loss, proline surge, and chlorosis in shoots, suggesting that ryegrass was highly sensitive to As. Transcriptomic analysis revealed that the transcription factor LpIRO2 mediated the upregulation of ZIP1 and YSL6 that played an important role in Cd tolerance. We found that the presence of As caused the overexpression of LpSWT12, a process potentially regulated by bHLH14, to mitigate hyperosmolarity. Indoleacetic acid (IAA) and abscisic acid (ABA) contents and expression of their signaling-related genes were significantly affected by As stress rather than Cd. We predict a regulatory network to illustrate the interaction between transporters, transcription factors, and signaling transduction, and explain the antagonism of Cd and As toxicity. This present work provides a research basis for plant protection from Cd and As pollution.

Chitosan-based supramolecular aerogel with "skeletal structure" constructed in natural deep eutectic solvents for medical dressings.

Bacterial infection of wounds remains one of the major clinical challenges, calling for the urgent development of novel multifunctional biological dressings. In this study, we developed a chitosan-based supramolecular aerogel NADES/PVA/CS, constructed by hydrogen bonding between chitosan, a natural deep eutectic solvents and polyvinyl alcohol, as a novel wound dressing against bacterial infections. The effect of polyvinyl alcohol content and its incorporation within chitosan-based supramolecular aerogels were investigated. The results of antibacterial test and MTT assay showed that it has obvious inhibitory effect on Staphylococcus aureus and Escherichia coli, showing excellent biocompatibility and effectively promotes wound healing. The microstructure of chitosan-based supramolecular aerogel showed that by adjusting the addition amount of polyvinyl alcohol, it could exhibit a perfect skeleton-type 3D network structure, which also made it possess smaller density and larger porosity and exhibit excellent water absorption property, contributing to the wetting of wound surface. More importantly, chitosan-based supramolecular aerogel is an environment-friendly biomaterial, which has been verified by degradability experiment. In a word, these unique advantages provide a broad prospect for the medical application of chitosan-based supramolecular aerogel NADES/PVA/CS, and provide a new strategy for the construction of green polysaccharide medical materials.

Study on the deacetylation and mechanism of chitin in natural deep eutectic solvent.

A large number of hydrogen bonds is the main reason for hindering the dissolution and reaction of chitin, and a mild and green deacetylation method to prepare chitosan for a wider range of applications is urgent. As a non-toxic and degradable green solvent, the deep eutectic solvent can effectively interfere with the hydrogen bond network of chitin, making chitin more susceptible to other solvents. Therefore, a NADES system consisting of betaine and glycerol was proposed for application in the deacetylation reaction of chitin to facilitate further attack of N-acetyl groups by low concentrations of NaOH. After optimizing the reaction conditions, chitosan with 83.77 % deacetylation was prepared, requiring only a concentration of 25 wt% NaOH. The analysis of the product chitosan showed that NADES could not only effectively improve the degree of deacetylation, but also reduce the degree of damage to the molecular weight by alkali. In addition, the potential mechanisms involved in the deacetylation process by NADES were explored. The nature of the reaction was verified by FT-IR, XRD and theoretical calculations as the process of opening intra/intermolecular hydrogen bonds of chitin by NADES. More importantly, experimental and in-depth theoretical studies provide a reference for the green preparation of chitosan.

High blood galectin-3 level associated with risk of frailty in aging.

Background: Frailty is one of the most problematic expressions of population aging, but its underlying mechanism has not been fully elucidated. Circulating galectin-3 (Gal-3) is involved in the pathogenesis of many age-related diseases. This study aims to explore the influence of circulating Gal-3 on the regulation of frailty and aging and to identify the potential mechanism further. Methods: In this cross-sectional analysis, the Fried frailty phenotype (FP) was assessed among 149 community elderly residents in Shanghai. Peripheral blood mononuclear cells (PBMCs) were isolated by the Ficoll-Paque density gradient method, and differentially expressed genes (DEGs) encoding transcription factors in frailty were detected by Illumina and bioinformatics analyzed with R software. Gene Ontology (GO) enrichment analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to explore the functional roles of these DEGs and the target genes related to frailty phenotypes. The serum Gal-3 concentration was tested by enzyme-linked immunosorbent assay (ELISA). Mouse frailty phenotype was used to construct an in vivo model of frailty, after which the serum levels of circulating Gal-3 and its gene expression levels in mouse tissues were determined. Results: Participants' mean age was 72.04 ± 7.05 years. In total, 21.48% were frail and 36.91% were pre-frail. The mean serum Gal-3 concentration was 46.34 ± 17.99 ng/mL in frail participants, 32.30 ± 8.14 ng/mL in pre-frail participants, and 26.00 ± 5.87 ng/mL in non-frail individuals (p < 0.001). Significant positive correlations between serum Gal-3 level and FP score, SARC-F score, C-reactive protein (CRP), interleukin-6, etc., were observed. In addition, the KEGG pathway and GO enrichment analyses showed that 265 DEGs in PBMCs of frail participants were mainly related to inflammatory response, translation, RNA binding, protein binding, ribosome, and primary immunodeficiency. LGALS3 was identified as the overlapping gene between frailty-related DEGs and aging-related DEGs. The elevated serum Gal-3 concentration in the in vivo model of frailty was consistent with the results in participants. Conclusion: In both community-dwelling older adults and aged mice, serum Gal-3 concentration was positively correlated with frailty. This circulating mediator may be a promising indicator of frailty. Clinical trial registration: Chinese Clinical Trial Registry identifier, ChiCTR2000036399.

Super-enhancer-driven MLX mediates redox balance maintenance via SLC7A11 in osteosarcoma.

Osteosarcoma (OS) is a common type of bone tumor for which there has been limited therapeutic progress over the past three decades. The prevalence of transcriptional addiction in cancer cells emphasizes the biological significance and clinical relevance of super-enhancers. In this study, we found that Max-like protein X (MLX), a member of the Myc-MLX network, is driven by super-enhancers. Upregulation of MLX predicts a poor prognosis in osteosarcoma. Knockdown of MLX impairs growth and metastasis of osteosarcoma in vivo and in vitro. Transcriptomic sequencing has revealed that MLX is involved in various metabolic pathways (e.g., lipid metabolism) and can induce metabolic reprogramming. Furthermore, knockdown of MLX results in disturbed transport and storage of ferrous iron, leading to an increase in the level of cellular ferrous iron and subsequent induction of ferroptosis. Mechanistically, MLX regulates the glutamate/cystine antiporter SLC7A11 to promote extracellular cysteine uptake required for the biosynthesis of the essential antioxidant GSH, thereby detoxifying reactive oxygen species (ROS) and maintaining the redox balance of osteosarcoma cells. Importantly, sulfasalazine, an FDA-approved anti-inflammatory drug, can inhibit SLC7A11, disrupt redox balance, and induce massive ferroptosis, leading to impaired tumor growth in vivo. Taken together, this study reveals a novel mechanism in which super-enhancer-driven MLX positively regulates SLC7A11 to meet the alleviated demand for cystine and maintain the redox balance, highlighting the feasibility and clinical promise of targeting SLC7A11 in osteosarcoma.

Responses of sediment nitrogen forms and bacterial communities to different aquatic nitrogen conditions in three submerged macrophyte-type ecological treatment systems.

Ecological treatment system (ETS) has been recognized as a promising technology for mitigating agricultural non-point pollution, whereas it remains to be seen how nitrogen (N) forms and bacterial communities in ETS sediments respond to different aquatic N conditions. Therefore, a four-month microcosm experiment was conducted to investigate the effects of three aquatic N conditions (2 mg/L NH4+-N, 2 mg/L NO3--N and 1 mg/L NH4+-N + 1 mg/L NO3--N) on sediment N forms and bacterial communities in three ETSs vegetated by Potamogeton malaianus, Vallisneria natans and artificial aquatic plant, respectively. Through analysis of four transferable N fractions, the valence states of N in ion-exchange and weak acid extractable fractions were found to be mainly determined by aquatic N conditions, while significant N accumulation was observed only in strong oxidant extractable and strong alkali extractable fractions. Sediment N profiles were primarily influenced by time and plant types, with N condition having secondary effect, while sediment bacterial community structures experienced a significant shift over time and were slightly influenced by plant types. Sediment functional genes related to N fixation, nitrification, assimilable nitrate reduction, dissimilatory nitrite reduction (DNRA) and denitrification were substantially enriched in month 4, and the bacterial co-occurrence network exhibited less complexity but more stability under NO3- condition compared to others. Furthermore, certain sediment N fractions were found to have strong relationships with specific sediment bacteria, such as nitrifiers, denitrifiers and DNRA bacteria. Our findings highlight the significant influence of aquatic N condition in submerged macrophyte-type ETSs on sediment N forms and bacterial communities.

Improved Bioproduction of the Nylon 12 Monomer by Combining the Directed Evolution of P450 and Enhancing Heme Synthesis.

The nylon 12 (PA12) monomer ω-aminododecanoic acid (ω-AmDDA) could be synthesized from lauric acid (DDA) through multi-enzyme cascade transformation using engineered E. coli, with the P450 catalyzing terminal hydroxylation of DDA as a rate-limiting enzyme. Its activity is jointly determined by the heme domain and the reductase domain. To obtain a P450 mutant with higher activity, directed evolution was conducted using a colorimetric high-throughput screening (HTS) system with DDA as the real substrate. After two rounds of directed evolution, a positive double-site mutant (R14R/D629G) with 90.3% higher activity was obtained. Molecular docking analysis, kinetic parameter determination and protein electrophoresis suggested the improved soluble expression of P450 resulting from the synonymous mutation near the N-terminus and the shortened distance of the electron transfer between FMN and FAD caused by D629G mutation as the major reasons for activity improvement. The significantly increased kcat and unchanged Km provided further evidence for the increase in electron transfer efficiency. Considering the important role of heme in P450, its supply was strengthened by the metabolic engineering of the heme synthesis pathway. By combining P450-directed evolution and enhancing heme synthesis, 2.02 ± 0.03 g/L of ω-AmDDA was produced from 10 mM DDA, with a yield of 93.6%.

Dynamic Light Scattering Based Microrheology of End-Functionalised Triblock Copolymer Solutions.

Nano-sized particles functionalised with short single-stranded (ss)DNAs can act as detectors of complementary DNA strands. Here we consider tri-block-copolymer-based, self-assembling DNA-coated nanoparticles. The copolymers are chemically linked to the DNA strands via azide (N3) groups. The micelles aggregate when they are linked with complementary ssDNA. The advantage of such block-copolymer-based systems is that they are easy to make. Here we show that DNA functionalisation results in inter-micellar attraction, but that N3-groups that have not reacted with the DNA detector strands also change the phase behaviour of the tri-block polymer solution. We studied the triblock copolymer, Pluronic® F108, which forms spherical micelles in aqueous solutions upon heating. We find that the triblock chains ending with either an N3 or N3-DNA complex show a dramatic change in phase behaviour. In particular, the N3-functionalisation causes the chain ends to cluster below the critical micelle temperature (CMT) of pure F108, forming flower-micelles with the N3-groups at the core, while the PPO groups are exposed to the solvent. Above the CMT, we see an inversion with the PPO chains forming the micellar core, while the N3-groups are now aggregating on the periphery, inducing an attraction between the micelles. Our results demonstrate that, due to the two competing self-assembling mechanisms, the system can form transient hydrogels.

Construction of chitosan-based supramolecular biofilm material for wound dressing based on natural deep eutectic solvents.

Bacterial infection is still one of the main problems observed in the clinical process of wound healing, so the development of new multifunctional biocompatible materials is an urgent clinical need. A kind of supramolecular biofilm crosslinked by hydrogen bond between natural deep eutectic solvent and chitosan was studied and successfully prepared to reduce bacterial infection. Its killing rates of Staphylococcus aureus and Escherichia coli can reach 98.86 % ± 1.90 % and 99.69 % ± 0.53 %, and it can be degraded in both soil and water, showing excellent biocompatibility and biodegradability. In addition, the supramolecular biofilm material also has the UV barrier property, which can effectively avoid the secondary injury of UV to the wound. Interestingly, the cross-linking effect of hydrogen bond makes the biofilm have a more compact structure and rough surface, and gives the biofilm strong tensile properties. Overall, owing to these unique advantages, NADES-CS supramolecular biofilm has great potential for medical applications, laying the foundation for the realization of sustainable polysaccharide materials.

A Cost-effectiveness Analysis of a Mobile Phone-Based Integrated HIV-Prevention Intervention Among Men Who Have Sex With Men in China: Economic Evaluation.

BACKGROUND: Mobile phone-based digital interventions have been shown to be a promising strategy for HIV prevention among men who have sex with men (MSM). OBJECTIVE: This study aimed to evaluate the cost-effectiveness of a mobile phone-based digital intervention for HIV prevention among MSM in China from the perspective of a public health provider. METHODS: The cost-effectiveness of the mobile phone-based digital intervention was estimated for a hypothetical cohort of 10,000 HIV-negative MSM who were followed for 1 year. A model was developed with China-specific data to project the clinical impact and cost-effectiveness of two mobile phone-based digital strategies for HIV prevention among MSM. The intervention group received an integrated behavioral intervention that included 1) individualized HIV infection risk assessment, 2) recommendation of centers testing for HIV and other STIs, 3) free online order of condoms and HIV and syphilis self-test kits and 4) educational materials about HIV/AIDS. The control group was only given educational materials about HIV/AIDS. Outcomes of interest were the number of HIV infections among MSM averted by the intervention, intervention costs, cost per HIV infection averted by the mobile phone-based digital intervention, and quality-adjusted life-years (QALYs). Univariate and multivariate sensitivity analyses were also conducted to examine the robustness of the results. RESULTS: It is estimated that the intervention can prevent 48 MSM from becoming infected with HIV and can save 480 QALYs. The cost of preventing 1 case of HIV infection was US $2599.87, and the cost-utility ratio was less than 0. Sensitivity analysis showed that the cost-effectiveness of the mobile phone-based digital intervention was mainly impacted by the average number of sexual behaviors with each sexual partner. Additionally, the higher the HIV prevalence among MSM, the greater the benefit of the intervention. CONCLUSIONS: Mobile phone-based digital interventions are a cost-effective HIV-prevention strategy for MSM and could be considered for promotion and application among high-risk MSM subgroups.

Lactobacillus salivarius Promotion of Intestinal Stem Cell Activity in Hens Is Associated with Succinate-Induced Mitochondrial Energy Metabolism.

Currently, the regulation of Lactobacillus on intestinal stem cells (ISCs) attracts broad attention, but their active ingredients and the underlying mechanism are worthy of further study. Previously, host intestinal commensal bacteria were verified to drive the differentiation of ISCs. In this study, the strong bacteriostatic activity of Lactobacillus salivarius and Lactobacillus agilis were illustrated, and the components (supernatant, precipitation) of L. salivarius or L. agilis were further demonstrated to decrease the differentiation of ISCs in vivo. Interestingly, antibiotics feeding decreased ISCs differentiation in vivo as well. However, the administration of L. salivarius supernatant following antibiotics feeding was shown to promote ISCs differentiation dramatically when compared with the antibiotics feeding group, indicating that some active ingredients existed in its supernatant to promote ISCs activity. Strikingly, in vitro, the treatment of L. salivarius supernatant was further confirmed to promote the intestinal organoids' size, budding, and LGR5 expression. Next, the metabolomics analysis of Lactobacilli' supernatants suggested that succinate might be a crucial metabolite to promote ISCs activity. Further, the succinate treatment in vitro (1000 µM) and in vivo (50 mM) was confirmed to enhance the expression of LGR5 and PCNA. SLC13A3 (a sodium/dicarboxylate cotransporter) was detected in the intestinal organoids and demonstrated to transport succinate into ISCs, as confirmed by the contact of FITC-succinate with ISCs nucleus. Subsequently, high mitochondrial membrane potential and reactive oxygen species levels appeared in the intestinal organoids upon succinate treatment. Collectively, the promotion of L. salivarius on ISCs activity is associated with succinate-induced mitochondrial energy metabolism. IMPORTANCE In our previous study, Lactobacillus salivarius and Lactobacillus agilis were demonstrated to regulate intestinal stem cell activity in hens, but their active ingredients and the underlying mechanism remain unclear. In this study, L. salivarius supernatant was shown to directly promote intestinal stem cell activity. Furthermore, the succinate (a critical metabolite of L. salivarius) was screened out to promote intestinal stem cell activity. Moreover, the succinate was confirmed to enter intestinal stem cells and induce high mitochondrial energy metabolism, finally promoting intestinal stem cell activity. These findings will advance uncovering the mechanism by which Lactobacillus regulate intestinal stem cell activity in chickens.