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1.
Huan Jing Ke Xue ; 45(7): 4352-4360, 2024 Jul 08.
Article in Chinese | MEDLINE | ID: mdl-39022979

ABSTRACT

Food waste is one of the important reservoirs of antibiotic resistance genes (ARGs), and its resource utilization has potential environmental risks. Anaerobic digestion (AD) technology can concurrently achieve resource recovery and ARGs removal, which is one of the popular resource technologies for food waste management. However, the removal efficiency of ARGs during the AD process is limited, and thus the safety of digestate for agricultural use is still questioned. Therefore, how to improve the performance of ARGs removal during the AD process is critical for efficient and environmentally friendly bioconversion of food waste. This study summarized the transmission pathways and mechanisms of ARGs in food waste; discussed the effects of different operation parameters on the transmission of ARGs in food waste during the AD process; described the research progress of exogenous addition of conductive materials, feedstock pretreatment, etc., strategies to enhance the removal of ARGs; and analyzed the migration regularity and removal mechanism of ARGs in food waste during the AD process, which mainly included microbial community structure evolution, mobile genetic element changes, and environmental factor changes. Finally, this study prospected the future improvement of methane yield and ARGs removal in the AD process of food waste based on the existing research.


Subject(s)
Drug Resistance, Microbial , Anaerobiosis , Drug Resistance, Microbial/genetics , Refuse Disposal/methods , Bioreactors/microbiology , Food , Biodegradation, Environmental , Food Loss and Waste
3.
Anal Chem ; 96(28): 11374-11382, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38949233

ABSTRACT

Plastic pollution represents a critical threat to soil ecosystems and even humans, as plastics can serve as a habitat for breeding and refuging pathogenic microorganisms against stresses. However, evaluating the health risk of plastispheres is difficult due to the lack of risk factors and quantification model. Here, DNA sequencing, single-cell Raman-D2O labeling, and transformation assay were used to quantify key risk factors of plastisphere, including pathogen abundance, phenotypic resistance to various stresses (antibiotic and pesticide), and ability to acquire antibiotic resistance genes. A Bayesian network model was newly introduced to integrate these three factors and infer their causal relationships. Using this model, the risk of pathogen in the plastisphere is found to be nearly 3 magnitudes higher than that in free-living state. Furthermore, this model exhibits robustness for risk prediction, even in the absence of one factor. Our framework offers a novel and practical approach to assessing the health risk of plastispheres, contributing to the management of plastic-related threats to human health.


Subject(s)
Bayes Theorem , Bacteria/genetics , Bacteria/isolation & purification , Phenotype , Soil Microbiology , Humans , Anti-Bacterial Agents/pharmacology
4.
J Colloid Interface Sci ; 675: 639-645, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38991278

ABSTRACT

The Zn dendrite limits the practical application of aqueous zinc-ion batteries in the large-scale energy storage systems. To suppress the growth of Zn dendrites, a zinc ionophore of hydroxychloroquine (defined as HCQ) applied in vivo treatment is investigated as the electrolyte additive. HCQ dynamically regulates zinc ion concentration in the outer Helmholtz layer, promoting even Zn plating at the anode/electrolyte interface. This is evidenced by the scanning electron microscopy, which delivers planar Zn plating after cycling. It is further supported by the X-ray diffraction spectroscopy, which reveals the growth of Zn (002) plane. Additionally, the reduced production of H2 during Zn plating/stripping is detected by the in-situ differential electrochemical mass spectrometry (DEMS), which shows the resistance of Zn (002) to hydrogen evolution reaction. The mechanism of dynamic regulation for zinc ion concentration is demonstrated by the in-situ optical microscopy. The hydrated zinc ion can be further plated more rapidly to the uneven location than the case in other regions, which is resulted from the dynamic regulation for zinc ion concentration. Therefore, the uniform Zn plating is formed. A cycling life of 1100 h is exhibited in the Zn||Zn symmetric cell at 1.6 mA cm-2 with the capacity of 1.6 mAh cm-2. The Zn||Cu battery exhibits a cycling life of 200 cycles at 4 mA cm-2 with a capacity of 4 mAh cm-2 and the average Coulombic efficiency is larger than 99 %. The Zn||VO2 battery with HCQ modified electrolyte can operate for 1500 cycles at 4 A g-1 with a capacity retention of 90 %. This strategy in the present work is wished to advance the development of zinc-ion batteries for practical application.

5.
Inorg Chem ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38996364

ABSTRACT

The recent report of planar tetracoordinate hydrogen (ptH) in In4H+ is very intriguing in planar hypercoordinate chemistry. Our high-level CCSD(T) calculations revealed that the proposed D4h-symmetric ptH In4H+ is a first-order saddle point with an imaginary frequency in the out-of-plane mode of the hydrogen atom. In fact, at the CCSD(T)/aug-cc-pV5Z/aug-cc-pV5Z-PP level, the C4v isomer, with the H atom located 0.70 Å above the In4 plane, is 0.5 kcal/mol more stable than the D4h isomer. However, given the small perturbation from planarity and essentially barrierless C4v ↔ D4h ↔ C4v transition, the vibrationally averaged structure can still be considered as a planar. Extending our exploration to the InnTl4-nH+ (n = 0-3) systems, we found all these ptH structures, except for In2Tl2H+, to be the putative global minimum. The single σ-delocalized interaction between the central hydrogen atom and InnTl4-n ligand rings proves pivotal in establishing planarity and aromaticity and conferring substantial stability upon these rule-breaking ptH species.

6.
JAMA Netw Open ; 7(7): e2423229, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39042407

ABSTRACT

Importance: Chronic pelvic pain (CPP) is the main sequela of pelvic inflammatory disease (PID), with no established treatment. ZY5301 tablets, an effective part preparation extracted from Ajuga decumbens Thunb. (jingucao), are being tested as a treatment for CPP caused by PID. Objective: To evaluate whether ZY5301 tablets are effective and safe for CPP treatment in women with PID. Design, Setting, and Participants: This placebo-controlled double-blind, dose-parallel, phase 2 randomized clinical trial was conducted in 9 hospitals in China. Female participants with CPP after PID were enrolled between October 16, 2020, and August 31, 2021. The data analysis was performed between December 2021 and March 2022. Interventions: Participants were randomized 1:1:1 to receive ZY5301 300 mg/d, ZY5301 600 mg/d, or placebo orally 3 times a day for 12 weeks. Main Outcomes and Measures: Visual analog scale (VAS) scores were the main measure used to evaluate the efficacy of ZY5301 in reducing CPP. The evaluation end points for VAS score included changes in mean weekly VAS score from baseline, area under the VAS score-time curve, pain remission (VAS score of 0 and 1) rate, and median time to pain remission. Safety was evaluated by the occurrence of treatment-emergent and treatment-related adverse events. Results: In total, 180 women were randomly assigned, and 177 were included in the efficacy analysis; thus, the full analysis set included 60 participants in the ZY5301 mg/d group (mean [SD] age, 37.4 [8.1] years), 58 in the ZY5301 600 mg/d group (mean [SD] age, 37.1 [7.9] years), and 59 in the placebo group (mean [SD] age, 38.9 [7.3] years). Participant characteristics at baseline were similar among the groups. After 12 weeks of treatment, the mean (SD) change in VAS score from the baseline was -2.1 (1.7) points, -3.5 (1.5) points, and -3.8 (1.7) points in the placebo, ZY5301 300 mg/d, and ZY5301 600 mg/d groups, respectively (P < .001). The pain remission rates at week 12 were 43.3% and 53.5% in the ZY5301 300 mg/d and ZY5301 600 mg/d groups, respectively, a significant difference compared with the placebo group (11.9%; P < .001). All the other end points showed similar improvements. The ZY5301 600 mg/d group had better efficacy than the ZY5301 300 mg/d group, but the difference was not significant. The safety analysis revealed no significant differences among groups. Conclusions and Relevance: These findings show that ZY5301 tablet is efficacious for the relief of CPP with acceptable tolerability. Trial Registration: ClinicalTrials.gov Identifier: NCT05460546.


Subject(s)
Pelvic Inflammatory Disease , Pelvic Pain , Humans , Female , Pelvic Pain/drug therapy , Pelvic Pain/etiology , Adult , Pelvic Inflammatory Disease/drug therapy , Double-Blind Method , Tablets , Chronic Pain/drug therapy , Chronic Pain/etiology , Middle Aged , Treatment Outcome , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/administration & dosage , Pain Measurement , China
7.
Hum Brain Mapp ; 45(11): e26790, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39037119

ABSTRACT

Brain glymphatic dysfunction is critical in neurodegenerative processes. While animal studies have provided substantial insights, understandings in humans remains limited. Recent attention has focused on the non-invasive evaluation of brain glymphatic function. However, its association with brain parenchymal lesions in large-scale population remains under-investigated. In this cross-sectional analysis of 1030 participants (57.14 ± 9.34 years, 37.18% males) from the Shunyi cohort, we developed an automated pipeline to calculate diffusion-weighted image analysis along the perivascular space (ALPS), with a lower ALPS value indicating worse glymphatic function. The automated ALPS showed high consistency with the manual calculation of this index (ICC = 0.81, 95% CI: 0.662-0.898). We found that those with older age and male sex had lower automated ALPS values (ß = -0.051, SE = 0.004, p < .001, per 10 years, and ß = -0.036, SE = 0.008, p < .001, respectively). White matter hyperintensity (ß = -2.458, SE = 0.175, p < .001) and presence of lacunes (OR = 0.004, 95% CI < 0.002-0.016, p < .001) were significantly correlated with decreased ALPS. The brain parenchymal and hippocampal fractions were significantly associated with decreased ALPS (ß = 0.067, SE = 0.007, p < .001 and ß = 0.040, SE = 0.014, p = .006, respectively) independent of white matter hyperintensity. Our research implies that the automated ALPS index is potentially a valuable imaging marker for the glymphatic system, deepening our understanding of glymphatic dysfunction.


Subject(s)
Diffusion Magnetic Resonance Imaging , Glymphatic System , Humans , Male , Female , Glymphatic System/diagnostic imaging , Glymphatic System/pathology , Glymphatic System/physiopathology , Middle Aged , Cross-Sectional Studies , Aged , Diffusion Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Brain/pathology , White Matter/diagnostic imaging , White Matter/pathology , Image Processing, Computer-Assisted/methods , Adult , Cohort Studies
8.
Int J Mol Sci ; 25(13)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39000365

ABSTRACT

Sorghum (Sorghum bicolor), the fifth most important cereal crop globally, serves as a staple food, animal feed, and a bioenergy source. Paclobutrazol-Resistance (PRE) genes play a pivotal role in the response to environmental stress, yet the understanding of their involvement in pest resistance remains limited. In the present study, a total of seven SbPRE genes were found within the sorghum BTx623 genome. Subsequently, their genomic location was studied, and they were distributed on four chromosomes. An analysis of cis-acting elements in SbPRE promoters revealed that various elements were associated with hormones and stress responses. Expression pattern analysis showed differentially tissue-specific expression profiles among SbPRE genes. The expression of some SbPRE genes can be induced by abiotic stress and aphid treatments. Furthermore, through phytohormones and transgenic analyses, we demonstrated that SbPRE4 improves sorghum resistance to aphids by accumulating jasmonic acids (JAs) in transgenic Arabidopsis, giving insights into the molecular and biological function of atypical basic helix-loop-helix (bHLH) transcription factors in sorghum pest resistance.


Subject(s)
Aphids , Gene Expression Regulation, Plant , Plant Proteins , Sorghum , Stress, Physiological , Triazoles , Sorghum/genetics , Sorghum/metabolism , Aphids/genetics , Aphids/physiology , Animals , Triazoles/pharmacology , Stress, Physiological/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified , Oxylipins/metabolism , Oxylipins/pharmacology , Cyclopentanes/metabolism , Cyclopentanes/pharmacology , Arabidopsis/genetics , Promoter Regions, Genetic , Multigene Family , Plant Growth Regulators/metabolism , Plant Growth Regulators/pharmacology , Phylogeny , Plant Diseases/parasitology , Plant Diseases/genetics , Genome, Plant
9.
Anal Chem ; 96(26): 10851-10859, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38912707

ABSTRACT

Mitochondrial Membrane Chromatography (MMC) is a bioaffinity chromatography technique developed to study the interaction between target proteins embedded in the mitochondrial membrane and their ligand compounds. However, the MMC stationary phases (MMSP) prepared by chemical immobilization are prone to nonspecific binding in candidate agent screening inevitably. To address these challenges, Twin Strep-Tag/Strep Tactin was employed to establish a specific affinity system in the present study. We prepared a carnitine palmitoyltransferase 1A (CPT1A) MMSP by specifically linking Strep-tactin-modified silica gel with the Twin Strep-Tag on the CPT1A-oriented mitochondrial membrane. This Twin Strep-Tag/Strep Tactin modified CPT1A/MMC method exhibited remarkably better retention behavior, longer stationary phase lifespan, and higher screening specificity compared with previous MMC systems with glutaraldehyde immobilization. We adopted the CPT1A-specific MMC system in screening CPT1A ligands from traditional Chinese medicines, and successfully identified novel candidate ligands: ononin, isoliquiritigenin, and aloe-emodin, from Glycyrrhiza uralensis Fisch and Senna tora (L.) Roxb extracts. Biological assessments illustrated that the compounds screened promote CPT1A enzyme activity without affecting CPT1A protein expression, as well as effectively reduce the lipid droplets and triglyceride levels in the high fat induction HepG2 cells. The results suggest that we have developed an MMC system, which is promising for studying the bioaffinity of mitochondrial membrane proteins to candidate compounds. This system provides a platform for a key step in mitochondrial medicine discovery, especially for bioactive molecule screening from complex herbal extracts.


Subject(s)
Carnitine O-Palmitoyltransferase , Lipid Metabolism , Mitochondrial Membranes , Humans , Carnitine O-Palmitoyltransferase/metabolism , Lipid Metabolism/drug effects , Mitochondrial Membranes/metabolism , Chromatography, Affinity , Ligands
10.
J Nanobiotechnology ; 22(1): 318, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38849914

ABSTRACT

Mitochondria occupy a central role in the biology of most eukaryotic cells, functioning as the hub of oxidative metabolism where sugars, fats, and amino acids are ultimately oxidized to release energy. This crucial function fuels a variety of cellular activities. Disruption in mitochondrial metabolism is a common feature in many diseases, including cancer, neurodegenerative conditions and cardiovascular diseases. Targeting tumor cell mitochondrial metabolism with multifunctional nanosystems emerges as a promising strategy for enhancing therapeutic efficacy against cancer. This review comprehensively outlines the pathways of mitochondrial metabolism, emphasizing their critical roles in cellular energy production and metabolic regulation. The associations between aberrant mitochondrial metabolism and the initiation and progression of cancer are highlighted, illustrating how these metabolic disruptions contribute to oncogenesis and tumor sustainability. More importantly, innovative strategies employing nanomedicines to precisely target mitochondrial metabolic pathways in cancer therapy are fully explored. Furthermore, key challenges and future directions in this field are identified and discussed. Collectively, this review provides a comprehensive understanding of the current state and future potential of nanomedicine in targeting mitochondrial metabolism, offering insights for developing more effective cancer therapies.


Subject(s)
Mitochondria , Nanomedicine , Neoplasms , Humans , Mitochondria/metabolism , Mitochondria/drug effects , Neoplasms/drug therapy , Neoplasms/metabolism , Nanomedicine/methods , Animals , Energy Metabolism/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Nanoparticles/chemistry , Drug Delivery Systems/methods
11.
J Phys Chem A ; 128(24): 4806-4813, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38839423

ABSTRACT

Recently, Guha and co-workers (Sarmah, K.; Kalita, A.; Purkayastha, S.; Guha, A. K. Pushing The Extreme of Multicentre Bonding: Planar Pentacoordinate Hydride. Angew. Chem. Int. Ed. 2024, e202318741) reported a highly intriguing bonding motif: planar pentacoordinate hydrogen (ppH) in Li5H6-, featuring C2v symmetry in the singlet state with two distinct H-Li (center-ring) bond distances. We herein revisited the potential energy surface of Li5H6- by using a target-oriented genetic algorithm. Our investigation revealed that the lowest-energy structure of Li5H6- exhibits a ppH configuration with very high D5h symmetry and a 1A1' electronic state. We did not find any electronic effect like Jahn-Teller distortion that could be responsible for lowering its symmetry. Moreover, our calculations demonstrated significant differences in the relative energies of other low-lying isomers. An energetically very competitive planar tetracoordinate hydrogen (ptH) isomer is also located, but it corresponds to a very shallow minimum on the potential energy surface depending on the used level of theory. Chemical bonding analyses, including AdNDP and EDA-NOCV, uncover that the optimal Lewis structure for Li5H6- involves H- ions stabilized by the Li5H5 crown. Surprisingly, despite the dominance of electrostatic interactions, the contribution from covalent bonding is also significant between ppH and the Li5H5 moiety, derived from H-(1s) → Li5H5 σ donation. Magnetically induced current density analysis revealed that due to minimal orbital overlap and the highly polar nature of the H-Li covalent interaction, the ppH exhibits local diatropic ring currents around the H centers, which fails to result in a global aromatic ring current. The coordination of Li5H6- with Lewis acids, BH3 and BMe3, instantly converts the ppH configuration to (quasi) ptH. These Lewis acid-bound ptH complexes show high electronic stability and high thermochemical stability against dissociation and, therefore, will be ideal candidates for the experimental realization.

12.
Microb Cell Fact ; 23(1): 183, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38902758

ABSTRACT

BACKGROUND: Chelerythrine is an important alkaloid used in agriculture and medicine. However, its structural complexity and low abundance in nature hampers either bulk chemical synthesis or extraction from plants. Here, we reconstructed and optimized the complete biosynthesis pathway for chelerythrine from (S)-reticuline in Saccharomyces cerevisiae using genetic reprogramming. RESULTS: The first-generation strain Z4 capable of producing chelerythrine was obtained via heterologous expression of seven plant-derived enzymes (McoBBE, TfSMT, AmTDC, EcTNMT, PsMSH, EcP6H, and PsCPR) in S. cerevisiae W303-1 A. When this strain was cultured in the synthetic complete (SC) medium supplemented with 100 µM of (S)-reticuline for 10 days, it produced up to 0.34 µg/L chelerythrine. Furthermore, efficient metabolic engineering was performed by integrating multiple-copy rate-limiting genes (TfSMT, AmTDC, EcTNMT, PsMSH, EcP6H, PsCPR, INO2, and AtATR1), tailoring the heme and NADPH engineering, and engineering product trafficking by heterologous expression of MtABCG10 to enhance the metabolic flux of chelerythrine biosynthesis, leading to a nearly 900-fold increase in chelerythrine production. Combined with the cultivation process, chelerythrine was obtained at a titer of 12.61 mg per liter in a 0.5 L bioreactor, which is over 37,000-fold higher than that of the first-generation recombinant strain. CONCLUSIONS: This is the first heterologous reconstruction of the plant-derived pathway to produce chelerythrine in a yeast cell factory. Applying a combinatorial engineering strategy has significantly improved the chelerythrine yield in yeast and is a promising approach for synthesizing functional products using a microbial cell factory. This achievement underscores the potential of metabolic engineering and synthetic biology in revolutionizing natural product biosynthesis.


Subject(s)
Benzophenanthridines , Metabolic Engineering , Saccharomyces cerevisiae , Metabolic Engineering/methods , Benzophenanthridines/metabolism , Benzophenanthridines/biosynthesis , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae/genetics , Biosynthetic Pathways
13.
BMC Plant Biol ; 24(1): 575, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890577

ABSTRACT

BACKGROUND: Salvia miltiorrhiza, a well-known traditional Chinese medicine, frequently suffers from replant diseases that adversely affect its quality and yield. To elucidate S. miltiorrhiza's metabolic adaptations to replant disease, we analyzed its metabolome and transcriptome, comparing normal and replant diseased plants for the first time. RESULTS: We identified 1,269 metabolites, 257 of which were differentially accumulated metabolites, and identified 217 differentially expressed genes. Integrated transcriptomic and metabolomic analyses revealed a significant up-regulation and co-expression of metabolites and genes associated with plant hormone signal transduction and flavonoid biosynthesis pathways in replant diseases. Within plant hormone signal transduction pathway, plants afflicted with replant disease markedly accumulated indole-3-acetic acid and abscisic acid, correlating with high expression of their biosynthesis-related genes (SmAmidase, SmALDH, SmNCED, and SmAAOX3). Simultaneously, changes in hormone concentrations activated plant hormone signal transduction pathways. Moreover, under replant disease, metabolites in the local flavonoid metabolite biosynthetic pathway were significantly accumulated, consistent with the up-regulated gene (SmHTC1 and SmHTC2). The qRT-PCR analysis largely aligned with the transcriptomic results, confirming the trends in gene expression. Moreover, we identified 10 transcription factors co-expressed with differentially accumulated metabolites. CONCLUSIONS: Overall, we revealed the key genes and metabolites of S. miltiorrhiza under replant disease, establishing a robust foundation for future inquiries into the molecular responses to combat replant stress.


Subject(s)
Gene Expression Profiling , Metabolic Networks and Pathways , Salvia miltiorrhiza , Transcriptome , Salvia miltiorrhiza/genetics , Salvia miltiorrhiza/metabolism , Metabolic Networks and Pathways/genetics , Metabolomics , Gene Expression Regulation, Plant , Plant Growth Regulators/metabolism , Metabolome , Signal Transduction/genetics , Flavonoids/metabolism
14.
J Am Chem Soc ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38843775

ABSTRACT

The quest for planar hypercoordinate atoms (phA) beyond six has predominantly focused on transition metals, with dodecacoordination being the highest reported thus far. Extending this bonding scenario to main-group elements, which typically lack d orbitals despite their larger atomic radius, has posed significant challenges. Intrigued by the potentiality of covalent bonding formation using the d orbitals of the heavier alkaline-earth metals (Ae = Ca, Sr, Ba), the so-called "honorary transition metals", we aim to push the boundaries of planar hypercoordination. By including rings formed by 12-15 atoms of boron-carbon and Ae centers, we propose a design scheme of 180 candidates with a phA. Further systematic screening, structural examination, and stability assessments identified 10 potential clusters with a planar hypercoordinate alkaline-earth metal (phAe) as the lowest-energy form. These unconventional structures embody planar dodeca-, trideca-, tetradeca-, and pentadecacoordinate atoms. Chemical bonding analyses reveal the important role of Ae d orbitals in facilitating covalent interactions between the central Ae atom and the surrounding boron-carbon rings, thereby establishing a new record for coordination numbers in the two-dimensional realm.

15.
Int J Biol Macromol ; 273(Pt 1): 133080, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38866284

ABSTRACT

In the intricate web of ecological relationships, pollinators such as the Italian honeybee (Apis mellifera) play a crucial role in maintaining biodiversity and agricultural productivity. This study focuses on the interactions between three neonicotinoid compounds and the honeybee's chemosensory protein 3 (CSP3), a key player in their olfactory system. Employing advanced spectroscopic techniques and molecular modeling, we explore the binding dynamics and conformational changes in CSP3 upon exposure to these pesticides. The research reveals that all three neonicotinoids considerably quench CSP3's fluorescence through a dynamic and static mixing mechanism, indicating a strong binding affinity, predominantly driven by hydrophobic interactions. UV-visible absorption, synchronous fluorescence, and 3D fluorescence spectra support slight changes in the microenvironment around the aromatic amino acids of CSP3. Circular dichroism spectra indicate a reduction in CSP3's α-helix content, suggesting structural alterations. Molecular docking and dynamics simulations further elucidate the binding modes and stability of these interactions, highlighting the role of specific amino acids in CSP3's binding cavity. Findings provide critical insights into molecular mechanisms by which neonicotinoids may impair honeybee chemosensory function, offering implications for designing safer pesticides and understanding the broader ecological impact of these chemicals on pollinator health.


Subject(s)
Insect Proteins , Molecular Docking Simulation , Molecular Dynamics Simulation , Neonicotinoids , Animals , Bees/drug effects , Bees/chemistry , Neonicotinoids/chemistry , Insect Proteins/chemistry , Insect Proteins/metabolism , Protein Binding , Structure-Activity Relationship , Models, Molecular , Spectrometry, Fluorescence , Spectrum Analysis , Circular Dichroism
16.
J Am Heart Assoc ; 13(10): e034145, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38761086

ABSTRACT

BACKGROUND: This study aims to investigate the temporal and spatial patterns of structural brain injury related to deep medullary veins (DMVs) damage. METHODS AND RESULTS: This is a longitudinal analysis of the population-based Shunyi cohort study. Baseline DMVs numbers were identified on susceptibility-weighted imaging. We assessed vertex-wise cortex maps and diffusion maps at both baseline and follow-up using FSL software and the longitudinal FreeSurfer analysis suite. We performed statistical analysis of global measurements and voxel/vertex-wise analysis to explore the relationship between DMVs number and brain structural measurements. A total of 977 participants were included in the baseline, of whom 544 completed the follow-up magnetic resonance imaging (age 54.97±7.83 years, 32% men, mean interval 5.56±0.47 years). A lower number of DMVs was associated with a faster disruption of white matter microstructural integrity, presented by increased mean diffusivity and radial diffusion (ß=0.0001 and SE=0.0001 for both, P=0.04 and 0.03, respectively), in extensive deep white matter (threshold-free cluster enhancement P<0.05, adjusted for age and sex). Of particular interest, we found a bidirectional trend association between DMVs number and change in brain volumes. Specifically, participants with mild DMVs disruption showed greater cortical enlargement, whereas those with severe disruption exhibited more significant brain atrophy, primarily involving clusters in the frontal and parietal lobes (multiple comparison corrected P<0.05, adjusted for age, sex, and total intracranial volume). CONCLUSIONS: Our findings posed the dynamic pattern of brain parenchymal lesions related to DMVs injury, shedding light on the interactions and chronological roles of various pathological mechanisms.


Subject(s)
Cerebral Veins , Humans , Male , Female , Middle Aged , Cerebral Veins/diagnostic imaging , Cerebral Veins/pathology , Longitudinal Studies , China/epidemiology , White Matter/diagnostic imaging , White Matter/pathology , Adult , Aged
17.
J Hazard Mater ; 474: 134729, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38805811

ABSTRACT

Climate change and human activities escalate the frequency and intensity of wildfires, threatening amphibian habitats and survival; yet, research on these impacts remains limited. Wildfire ash alters water quality, introduces contaminants, and may disrupt microbial communities, impacting gut and skin microbiota; however, the effects on gut and skin microbiota remain unclear. Rana dybowskii were exposed to five concentrations (0 g L-1, 1.25 g L-1, 2.5 g L-1, 5 g L-1, and 10 g L-1) of aqueous extracts of wildfire ashes (AEAs) for 30 days to assess AEAs' metal content, survival, and microbiota diversity via Illumina sequencing. Our results showed that the major elements in ash were Ca > K > Mg > Al > Fe > Na > Mn, while in AEA they were K > Ca > Na > Mg > As > Al > Cu. A significant decrease in amphibian survival rates with increased AEA concentration was shown. The beta diversity analysis revealed distinct shifts in microbiota composition. Notably, bacterial genera associated with potential health risks showed increased abundance in skin microbiota, emphasising the potential for ash exposure to affect amphibian health. Functional prediction analyses revealed significant shifts in metabolic pathways related to health and disease, indicating that wildfire ash exposure may influence amphibian health through changes in microbial functions. This study highlights the urgent need for strategies to mitigate wildfire ash impacts on amphibians, as it significantly alters microbiota and affects their survival and health.


Subject(s)
Gastrointestinal Microbiome , Ranidae , Skin , Wildfires , Animals , Skin/drug effects , Skin/microbiology , Gastrointestinal Microbiome/drug effects , Ranidae/microbiology , Microbiota/drug effects , Bacteria/genetics , Bacteria/classification , Bacteria/drug effects , Bacteria/metabolism , Metals/toxicity
18.
Environ Pollut ; 355: 124197, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38782163

ABSTRACT

The presence and accumulation of both, plastics and antibiotics in soils may lead to the colonization, selection, and propagation of soil bacteria with certain metabolic traits, e.g., antibiotic resistance, in the plastisphere. However, the impact of plastic-antibiotic tandem on the soil ecosystem functioning, particularly on microbial function and metabolism remains currently unexplored. Herein, we investigated the competence of soil bacteria to colonize plastics and degrade 13C-labeled sulfamethoxazole (SMX). Using single-cell imaging, isotope tracers, soil respiration and SMX mineralization bulk measurements we show that microbial colonization of polyethylene (PE) and polystyrene (PS) surfaces takes place within the first 30 days of incubation. Morphologically diverse microorganisms were colonizing both plastic types, with a slight preference for PE substrate. CARD-FISH bacterial cell counts on PE and PS surfaces formed under SMX amendment ranged from 5.36 × 103 to 2.06 × 104, and 2.06 × 103 to 3.43 × 103 hybridized cells mm-2, respectively. Nano-scale Secondary Ion Mass Spectrometry measurements show that 13C enrichment was highest at 130 days with values up to 1.29 atom%, similar to those of the 13CO2 pool (up to 1.26 atom%, or 22.55 ‰). Independent Mann-Whitney U test showed a significant difference between the control plastisphere samples incubated without SMX and those in 13C-SMX incubations (P < 0.001). Our results provide direct evidence demonstrating, at single-cell level, the capacity of bacterial colonizers of plastics to assimilate 13C-SMX from contaminated soils. These findings expand our knowledge on the role of soil-seeded plastisphere microbiota in the ecological functioning of soils impacted by anthropogenic stressors.


Subject(s)
Soil Microbiology , Soil Pollutants , Soil , Sulfamethoxazole , Sulfamethoxazole/metabolism , Soil Pollutants/metabolism , Soil/chemistry , Single-Cell Analysis , Bacteria/metabolism , Carbon Isotopes , Plastics/metabolism , Anti-Bacterial Agents , Spectrometry, Mass, Secondary Ion
19.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(5): 481-485, 2024 May 15.
Article in Chinese | MEDLINE | ID: mdl-38802908

ABSTRACT

OBJECTIVES: To investigate the differences in clinical characteristics among children on prolonged mechanical ventilation (PMV) due to different primary diseases. METHODS: A retrospective analysis was performed on the clinical data of 59 pediatric patients requiring PMV from July 2017 to September 2022. According to the primary disease, they were divided into respiratory disease (RD) group, central nervous system (CNS) group, neuromuscular disease (NMD) group, and other disease group. The four groups were compared in terms of general information, treatment, and outcome. RESULTS: There were significant differences among the four groups in age, body weight, Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score, Pediatric Risk of Mortality III (PRISM Ⅲ) score, analgesic and sedative treatment, nutrition supply, rehabilitation treatment, tracheotomy, successful ventilator weaning, and outcomes (P<0.05). Compared with the RD group, the CNS group and the other disease group had a significantly higher age and a significantly higher proportion of children receiving rehabilitation treatment, and the CNS group had a significantly higher proportion of children receiving tracheotomy (P<0.008). Compared with the other disease group, the CNS group and the NMD group had significantly lower PELOD-2 and PRISM III scores, and the CNS group had a significantly higher proportion of children with successful ventilator weaning and a significantly higher proportion of children who were improved and discharged (P<0.008). CONCLUSIONS: There are differences in clinical characteristics among children receiving PMV due to different etiologies. Most children in the RD group have a younger age, and children in the CNS group have a relatively good prognosis.


Subject(s)
Neuromuscular Diseases , Respiration, Artificial , Humans , Male , Female , Retrospective Studies , Child, Preschool , Infant , Neuromuscular Diseases/therapy , Neuromuscular Diseases/etiology , Child , Central Nervous System Diseases/etiology , Central Nervous System Diseases/therapy , Respiratory Tract Diseases/therapy , Respiratory Tract Diseases/etiology
20.
Cell Death Dis ; 15(5): 307, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693104

ABSTRACT

The interplay between extracellular matrix (ECM) stiffness and the tumor microenvironment is increasingly recognized as a critical factor in cancer progression and the efficacy of immunotherapy. This review comprehensively discusses the key factors regulating ECM remodeling, including the activation of cancer-associated fibroblasts and the accumulation and crosslinking of ECM proteins. Furthermore, it provides a detailed exploration of how ECM stiffness influences the behaviors of both tumor and immune cells. Significantly, the impact of ECM stiffness on the response to various immunotherapy strategies, such as immune checkpoint blockade, adoptive cell therapy, oncolytic virus therapy, and therapeutic cancer vaccines, is thoroughly examined. The review also addresses the challenges in translating research findings into clinical practice, highlighting the need for more precise biomaterials that accurately mimic the ECM and the development of novel therapeutic strategies. The insights offered aim to guide future research, with the potential to enhance the effectiveness of cancer immunotherapy modalities.


Subject(s)
Extracellular Matrix , Immunotherapy , Neoplasms , Tumor Microenvironment , Humans , Extracellular Matrix/metabolism , Immunotherapy/methods , Neoplasms/therapy , Neoplasms/immunology , Neoplasms/pathology , Tumor Microenvironment/immunology , Animals
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