Imaging phenotyping using 18F-FDG PET/CT radiomics to predict micropapillary and solid pattern in lung adenocarcinoma.

OBJECTIVES: To develop and validate a machine learning model using 18F-FDG PET/CT radiomics signature and clinical features to predict the presence of micropapillary and solid (MP/S) components in lung adenocarcinoma. METHODS: Eight hundred and forty-six patients who underwent preoperative PET/CT with pathologically confirmed adenocarcinoma were enrolled. After segmentation, 1688 radiomics features were extracted from PET/CT and selected to construct predictive models. Then, we developed a nomogram based on PET/CT radiomics integrated with clinical features. Receiver operating curves, calibration curves, and decision curve analysis (DCA) were performed for diagnostics assessment and test of the developed models for distinguishing patients with MP/S components from the patients without. RESULTS: PET/CT radiomics-clinical combined model could well distinguish patients with MP/S components from those without MP/S components (AUC = 0.87), which performed better than PET (AUC = 0.829, p < 0.05) or CT (AUC = 0.827, p < 0.05) radiomics models in the training cohort. In test cohorts, radiomics-clinical combined model outperformed the PET radiomics model in test cohort 1 (AUC = 0.859 vs 0.799, p < 0.05) and the CT radiomics model in test cohort 2 (AUC = 0.880 vs 0.829, p < 0.05). Calibration curve indicated good coherence between all model prediction and the actual observation in training and test cohorts. DCA revealed PET/CT radiomics-clinical model exerted the highest clinical benefit. CONCLUSION: 18F-FDG PET/CT radiomics signatures could achieve promising prediction efficiency to identify the presence of MP/S components in adenocarcinoma patients to help the clinician decide on personalized treatment and surveillance strategies. The PET/CT radiomics-clinical combined model performed best. CRITICAL RELEVANCE STATEMENT: 18F-FDG PET/CT radiomics signatures could achieve promising prediction efficiency to identify the presence of micropapillary and solid components in adenocarcinoma patients to help the clinician decide on personalized treatment and surveillance strategies.

Identification of Parkinson's disease and multiple system atrophy using multimodal PET/MRI radiomics.

OBJECTIVES: To construct a machine learning model for differentiating Parkinson's disease (PD) and multiple system atrophy (MSA) by using multimodal PET/MRI radiomics and clinical characteristics. METHODS: One hundred and nineteen patients (81 with PD and 38 with MSA) underwent brain PET/CT and MRI to obtain metabolic images ([18F]FDG, [11C]CFT PET) and structural MRI (T1WI, T2WI, and T2-FLAIR). Image analysis included automatic segmentation on MRI, co-registration of PET images onto the corresponding MRI. Radiomics features were then extracted from the putamina and caudate nuclei and selected to construct predictive models. Moreover, based on PET/MRI radiomics and clinical characteristics, we developed a nomogram. Receiver operating characteristic (ROC) curves were performed to evaluate the performance of the models. Decision curve analysis (DCA) was employed to access the clinical usefulness of the models. RESULTS: The combined PET/MRI radiomics model of five sequences outperformed monomodal radiomics models alone. Further, PET/MRI radiomics-clinical combined model could perfectly distinguish PD from MSA (AUC = 0.993), which outperformed the clinical model (AUC = 0.923, p = 0.028) in training set, with no significant difference in test set (AUC = 0.860 vs 0.917, p = 0.390). However, no significant difference was found between PET/MRI radiomics-clinical model and PET/MRI radiomics model in training (AUC = 0.988, p = 0.276) and test sets (AUC = 0.860 vs 0.845, p = 0.632). DCA demonstrated the highest clinical benefit of PET/MRI radiomics-clinical model. CONCLUSIONS: Our study indicates that multimodal PET/MRI radiomics could achieve promising performance to differentiate between PD and MSA in clinics. CLINICAL RELEVANCE STATEMENT: This study developed an optimal radiomics signature and construct model to distinguish PD from MSA by multimodal PET/MRI imaging methods in clinics for parkinsonian syndromes, which achieved an excellent performance. KEY POINTS: •Multimodal PET/MRI radiomics from putamina and caudate nuclei increase the diagnostic efficiency for distinguishing PD from MSA. •The radiomics-based nomogram was developed to differentiate between PD and MSA. •Combining PET/MRI radiomics-clinical model achieved promising performance to identify PD and MSA.

Environmental concentrations of anionic surfactants in lake surface microlayers enhance the toxicity of Microcystis blooms: Insight from photosynthesis, interspecies competition, and MC production.

Anionic surfactants represented by linear alkylbenzene sulfonate (LAS) exhibit vertical heterogeneity of concentrations in aquatic environments owing to their amphiphilic structure. Field investigations showed that the concentration of anionic surfactants (mainly LAS) in the water surface microlayer (SML) of Lake Taihu reached 580 µg/L, higher than that in the lower layer. Floating Microcystis blooms overlap in space with the high concentration of anionic surfactants in SML. However, few studies have focused on the effects of anionic surfactants (e.g., LAS) on the interspecies competition between toxic and nontoxic Microcystis. In this study, coculture and monoculture experiments were conducted with both toxic and nontoxic Microcystis species to explore how the environmental concentration of LAS regulates the dominance of toxic Microcystis and toxicity from the perspective of photosynthesis, species dominance, and MC production. The results showed that LAS concentrations above 0.267 or 0.431 mg/L (depending on light conditions) selectively promoted the photosynthetic competitive advantage of toxic Microcystis, leading to its higher population proportion in the community. Additionally, LAS concentrations above 0.5 mg/L induced the synthesis and release of microcystins (MCs). The results of chlorophyll fluorescence analysis, electron microscopy and transcriptome sequencing suggested that compared with nontoxic Microcystis, toxic Microcystis can better resist LAS stress by dissipating excess light, maintaining an intact membrane structure and maintaining cellular homeostasis. Transcriptome sequencing revealed that the photosynthetic damage of nontoxic Microcystis might be attributed to the impacts of LAS on the absorption and assimilation of nitrogen, which finally resulted in the degradation of phycobilisomes. This study can provide novel insight for establishing standards and safety management of wastewater discharge.

Habitat-specific environmental factors regulate the spatial variability of biological soil crust microbial communities on the Qinghai-Tibet Plateau.

Biological soil crusts (BSCs) are an important biological component of the soil surface, covering approximately 12 % of the Earth's land surface. Although BSCs are closely related to habitats, the microbial diversity and spatial variability of BSCs in different ecosystems are still unclear, especially on the Qinghai-Tibet Plateau (QTP), where climate is changeable and habitats are complex. Here, we investigated the diversity, assembly processes, spatial distribution pattern and driving factors of prokaryotic and eukaryotic microbial communities in BSCs in four habitats on the QTP. It was found that habitat-specific environmental factors regulated the composition, diversity and spatial variability of BSC microbial communities. Soil organic carbon and soil water content were the most important factors (R2 = 0.9024, P = 0.001; R2 = 0.8004, P = 0.001) affecting the spatial differences in prokaryotes and eukaryotes, respectively. Under the specific climate of the QTP, the spatial pattern of microbial communities in BSCs was controlled by precipitation rather than temperature. In addition, ecological processes further explained the effects of habitat specificity, and environmental filtering explained microbial community differences better than dispersal limitation. The results of the neutral community model and the normalized stochastic ratio index revealed that the assembly of prokaryotic communities was determined by deterministic processes at the regional scale, and at the local scale, the assembly process was mainly determined by habitat type, while the assembly of eukaryotic communities was determined by stochastic processes at both the regional and local scales. This study provided a scientific reference for the prediction of BSC distribution and resource conservation under future climate change scenarios.

Displays of 18 F-FAPI PET/CT in Myocarditis With Variable Symptom Durations.

ABSTRACT: We report cardiac 18 F-FAPI PET/CT findings in 3 cases with myocarditis of varying duration (7 hours, 1 week, and 1 month). Myocarditis with varying symptom durations showed different 18 F-FAPI uptake, suggesting that the 18 F-FAPI PET/CT may be helpful in evaluating the extent of fibrosis caused by myocarditis. This information may assist in treatment decision-making for patients with myocarditis.

Network Analysis Indicates Microbial Assemblage Differences in Life Stages of Cladophora.

Cladophora represents a microscopic forest that provides many ecological niches and fosters a diverse microbiota. However, the microbial community on Cladophora in brackish lakes is still poorly understood. In this study, the epiphytic bacterial communities of Cladophora in Qinghai Lake were investigated at three life stages (attached, floating, and decomposing). We found that in the attached stage, Cladophora was enriched with chemoheterotrophic and aerobic microorganisms, including Yoonia-Loktanella and Granulosicoccus. The proportion of phototrophic bacteria was higher in the floating stage, especially Cyanobacteria. The decomposing stage fostered an abundance of bacteria that showed vertical heterogeneity from the surface to the bottom. The surface layer of Cladophora contained mainly stress-tolerant chemoheterotrophic and photoheterotrophic bacteria, including Porphyrobacter and Nonlabens. The microbial community in the middle layer was similar to that of floating-stage Cladophora. Purple oxidizing bacteria were enriched in the bottom layer, with Candidatus Chloroploca, Allochromatium, and Thiocapsa as the dominant genera. The Shannon and Chao1 indices of epibiotic bacterial communities increased monotonically from the attached stage to the decomposing stage. Microbial community composition and functional predictions indicate that a large number of sulfur cycle-associated bacteria play an important role in the development of Cladophora. These results suggest that the microbial assemblage on Cladophora in a brackish lake is complex and contributes to the cycling of materials. IMPORTANCE Cladophora represents a microscopic forest that provides many ecological niches fostering a diverse microbiota, with a complex and intimate relationship between Cladophora and bacteria. Many studies have focused on the microbiology of freshwater Cladophora, but the composition and succession of microorganisms in different life stages of Cladophora, especially in brackish water, have not been explored. In this study, we investigated the microbial assemblages in the life stages of Cladophora in the brackish Qinghai Lake. We show that heterotrophic and photosynthetic autotrophic bacteria are enriched in attached and floating Cladophora, respectively, whereas the epiphytic bacterial community shows vertical heterogeneity in decomposing mats.

Geosmin disrupts energy metabolism and locomotor behavior of zebrafish in early life stages.

Geosmin has been commonly detected both in various aquatic environments and biota, but its exact toxicological mechanisms to organisms need further experimentation. In the present study, zebrafish embryos were exposed to geosmin at nominal concentrations of 50, 500 and 5000 ng/L for 120 h post-fertilization (hpf), followed by locomotor activity and biochemical parameter examination, and multi-omics investigation of the transcriptome and metabolome. The results showed that geosmin exposure significantly reduced the mitochondrial electron transport chain (ETC) complexes I-V, ATP content and mitochondrial respiration and suppressed the locomotor behavior of zebrafish larvae. Transcriptomics analysis revealed that the transcripts of genes involved in oxidative phosphorylation, glycolysis, and lipid metabolism were significantly affected, indicating that geosmin disrupts energy metabolism. Furthermore, metabolomics results showed that 3 classes of lipids, namely glycerophospholipids (GPs), sphingolipids (SLs) and fatty acyls (FAs) were significantly decreased after geosmin exposure. This study provides novel insight into the underlying mechanisms of geosmin-induced energy metabolism and highlights the need for concern about geosmin exposure.

Mucus-penetrating dendritic mesoporous silica nanoparticle loading drug nanocrystal clusters to enhance permeation and intestinal absorption.

Multiple gastrointestinal barriers (mucus clearance and epithelium barrier) are the main challenges in the oral administration of nanocarriers. To achieve efficient mucus penetration and epithelial absorption, a novel strategy based on mesoporous silica nanoparticles with dendritic superstructure, hydrophilicity, and nearly neutral-charged modification was designed. The mPEG covalently grafted dendritic mesoporous silica nanoparticles (mPEG-DMSNs) had a particle size of about 200 nm and a loading capacity of up to 50% andrographolide (AG) as a nanocrystal cluster in the mesoporous structure. This dual strategy of combining with the surface topography structure and hydrophilic modification maintained a high mucus permeability and showed an increase in cell absorption. The mPEG-DMSN formulation also exhibited effective transepithelial transport and intestinal tract distribution. The pharmacokinetics study demonstrated that compared with other AG formulations, the andrographolide nanocrystals-loaded mPEG-DMSN (AG@mPEG-DMSN) exhibited much higher bioavailability. Also, AG@mPEG-DMSN could significantly improve the in vitro and in vivo anti-inflammatory efficacy of AG. In summary, mPEG-DMSN offers an interesting strategy to overcome the mucus clearance and epithelium barriers of the gastrointestinal tract.

Revealing the Characteristics of Glucose- and Lactate-Based Chain Elongation for Caproate Production by Caproicibacterium lactatifermentans through Transcriptomic, Bioenergetic, and Regulatory Analyses.

Caproate, an important medium-chain fatty acid, can only be synthesized by limited bacterial species by using ethanol, lactate, or certain saccharides. Caproicibacterium lactatifermentans is a promising caproate producer due to its glucose and lactate utilization capabilities. However, the global cellular responses of this bacterium to different carbon sources were not well understood. Here, C. lactatifermentans showed robust growth on glucose but more active caproate synthesis on lactate. Comparative transcriptome revealed that the genes involved in reverse ß-oxidation for caproate synthesis and V-type ATPase-dependent ATP generation were upregulated under lactate condition, while several genes responsible for biomass synthesis were upregulated under glucose condition. Based on metabolic pathway reconstructions and bioenergetics analysis, the biomass accumulation on glucose condition may be supported by sufficient supplies of ATP and metabolite intermediates via glycolysis. In contrast, the ATP yield per glucose equivalent from lactate conversion into caproate was only 20% of that from glucose. Thus, the upregulation of the reverse ß-oxidation genes may be essential for cell survival under lactate conditions. Furthermore, the remarkably decreased lactate utilization was observed after glucose acclimatization, indicating the negative modulation of lactate utilization by glucose metabolism. Based on the cotranscription of the lactate utilization repressor gene lldR with sugar-specific PTS genes and the opposite expression patterns of lldR and lactate utilization genes, a novel regulatory mechanism of glucose-repressed lactate utilization mediated via lldR was proposed. The results of this study suggested the molecular mechanism underlying differential physiologic and metabolic characteristics of C. lactatifermentans grown on glucose and lactate. IMPORTANCE Caproicibacterium lactatifermentans is a unique and robust caproate-producing bacterium in the family Oscillospiraceae due to its lactate utilization capability, whereas its close relatives such as Caproicibacterium amylolyticum, Caproiciproducens galactitolivorans, and Caproicibacter fermentans cannot utilize lactate but produce lactate as the main fermentation end product. Moreover, C. lactatifermentans can also utilize several saccharides such as glucose and maltose. Although the metabolic versatility of the bacterium makes it to be a promising industrial caproate producer, the cellular responses of C. lactatifermentans to different carbon sources were unknown. Here, the molecular mechanisms of biomass synthesis supported by glucose utilization and the cell survival supported by lactate utilization were revealed. A novel insight into the regulatory machinery in which glucose negatively regulates lactate utilization was proposed. This study provides a valuable basis to control and optimize caproate production, which will contribute to achieving a circular economy and environmental sustainability.

Gradient rise in seepage pollution levels in tailings ponds shapes closer linkages between phytoplankton and bacteria.

A large number of tailings ponds formed by slag accumulation have become serious environmental hazards. Spatially high potential energy and long-term accumulation may result in gradient-changing seepage pollution. The assemblages of phytoplankton and bacteria are widely used as assessment indicators. In this study, we investigate the changes in phytoplankton and bacterial assemblages in tailing pollution. The results showed that there are temporal and spatial variabilities in seepage pollution. The abundance and diversity of phytoplankton and bacteria decreased with increasing pollution. However, Synedra acus (diatom) and Polynucleobacter (bacteria) were positively correlated with pollution levels (r = 0.37, P < 0.05; r = 0.24, P < 0.05). Heavy metals are the main contributors to bacterial changes (16.46%), while nutrients are for algae (13.24%). Tailings pond pollution reduced the number of phytoplankton and bacterial linkages. However, more pollution broke the originally independent modules of phytoplankton and bacteria, and they produced more positive correlations (79.39%; 87.68%). Microcystis sp. and Limnobacter were the key nodes of the co-occurrence network in the polluted areas. Exploring the interactions between bacteria and phytoplankton within different pollution levels could provide insights into biological interaction patterns and the bioremediation of tailings ponds.

A Machine Learning Model Based on PET/CT Radiomics and Clinical Characteristics Predicts Tumor Immune Profiles in Non-Small Cell Lung Cancer: A Retrospective Multicohort Study.

Background: The tumor immune microenvironment (TIME) phenotypes have been reported to mainly impact the efficacy of immunotherapy. Given the increasing use of immunotherapy in cancers, knowing an individual's TIME phenotypes could be helpful in screening patients who are more likely to respond to immunotherapy. Our study intended to establish, validate, and apply a machine learning model to predict TIME profiles in non-small cell lung cancer (NSCLC) by using 18F-FDG PET/CT radiomics and clinical characteristics. Methods: The RNA-seq data of 1145 NSCLC patients from The Cancer Genome Atlas (TCGA) cohort were analyzed. Then, 221 NSCLC patients from Daping Hospital (DPH) cohort received18F-FDG PET/CT scans before treatment and CD8 expression of the tumor samples were tested. The Artificial Intelligence Kit software was used to extract radiomic features of PET/CT images and develop a radiomics signature. The models were established by radiomics, clinical features, and radiomics-clinical combination, respectively, the performance of which was calculated by receiver operating curves (ROCs) and compared by DeLong test. Moreover, based on radiomics score (Rad-score) and clinical features, a nomogram was established. Finally, we applied the combined model to evaluate TIME phenotypes of NSCLC patients in The Cancer Imaging Archive (TCIA) cohort (n = 39). Results: TCGA data showed CD8 expression could represent the TIME profiles in NSCLC. In DPH cohort, PET/CT radiomics model outperformed CT model (AUC: 0.907 vs. 0.861, P = 0.0314) to predict CD8 expression. Further, PET/CT radiomics-clinical combined model (AUC = 0.932) outperformed PET/CT radiomics model (AUC = 0.907, P = 0.0326) or clinical model (AUC = 0.868, P = 0.0036) to predict CD8 expression. In the TCIA cohort, the predicted CD8-high group had significantly higher immune scores and more activated immune pathways than the predicted CD8-low group (P = 0.0421). Conclusion: Our study indicates that 18F-FDG PET/CT radiomics-clinical combined model could be a clinically practical method to non-invasively detect the tumor immune status in NSCLCs.

ß-Ionone causes endocrine disruption, hyperpigmentation and hypoactivity in zebrafish early life stages.

In nature, the odorous substance ß-ionone has been widely detected in aquatic ecosystems. However, little is known about its ecotoxicological effects on freshwater vertebrates. In this study, we aimed to assess the acute toxicity of ß-ionone in zebrafish (Danio rerio) embryos from 2 to 120 h post fertilization (hpf) and investigate embryo development, locomotor behavior and pigmentation under different concentrations. The results showed that exposure to ß-ionone had an acute toxicity to early life stages of zebrafish and induced a decrease in hatching rate and an increase in the mortality and malformation rate. The median lethal concentration (LC50) of ß-ionone at 96 h was observed as 1321 µg/L. In addition, ß-ionone not only affected the body length of zebrafish larvae but also regulated the transcription of genes and the levels of hormones involved in the growth hormone/insulin-like growth factor (GH/IGF) and the hypothalamic-pituitary-thyroid (HPT) axes. Moreover, exposure to ß-ionone induced significant decreases in locomotor activity and catecholamine neurotransmitters levels. Furthermore, ß-ionone stimulated pigmentation via regulation of tyrosinase activity and melanin-related gene expression. Overall, this research could provide new insights into the potential risk of odorants to aquatic organisms.

Environmental factors associated with the filamentous green algae Cladophora blooms: A mesocosm experiment in a shallow eutrophic lake.

The process of ecological restoration in eutrophic lakes, often results in the blooming of the filamentous green algae Cladophora. This consequently affects the growth of submerged plants and the restoration of vegetation. However, the blooming process of Cladophora and the environmental factors affecting their growth are poorly understood. This has become a difficult problem in the management of lakes. The study therefore focused on succession process of Cladophora blooms and their driving factors through mesocosm experiments in Caohai Lake. The results of our experiment indicated that Cladophora growth was mainly affected by water temperature, turbidity and soluble reactive phosphorus concentration of the habitat where Elodea nuttallii and Cladophora coexist. Nuisance Cladophora was mainly affected by turbidity (>19.24 NTU) when the water temperature was above 15.7 °C. With increasing Cladophora biomass and decreasing turbidity (<4.88 NTU), Cladophora biomass accumulation was mainly limited by the soluble reactive phosphorus concentration (<3.2 µg/L). Recorded turbidity range of 9.54-13.19 NTU was found to cause dramatic changes in the biomass of Cladophora. The results also showed that the outbreak of Cladophora blooms was mainly attributed to turbidity when the water temperature was appropriate in eutrophic lakes. These findings suggest that successful management efforts should strengthen the monitoring of transparency change in addition to controlling the phosphorus concentration to limit the Cladophora overgrowth on lake ecological restoration.

Dual-imaging magnetic nanocatalysis based on Fenton-like reaction for tumor therapy.

Sequential nano-catalytic therapy has emerged as a novel therapeutic modality for cancer treatment as it utilizes the unique tumor microenvironment for selective tumor treatment. This study reports a magnetic nanoparticle to achieve Fenton-like reaction and dual-imaging guidance/monitoring. Natural glucose oxidase (GOx) and superparamagnetic Fe3O4 nanoparticles have been integrated into poly(lactic-co-glycolic acid) (PLGA) to fabricate a sequential nanocatalyst (designated as GOx@PLGA-Fe3O4). This nanocatalyst can functionally deplete glucose in tumor tissues, producing a considerable amount of highly cytotoxic hydroxyl radicals via the sequential Fenton-like reaction, and meanwhile maximizing the potential imaging capability as a contrast agent for magnetic resonance imaging and photoacoustic imaging. By ribonucleic acid sequencing (RNA-seq) technology, GOx@PLGA-Fe3O4 nanoparticles are demonstrated to induce tumor cell death by inhibiting multiple gene regulation pathways involving tumor growth and recurrence. Therefore, this finding provides a novel strategy to achieve promising therapeutic efficacy by the rational design of multifunctional nanoparticles with various features, including magnetic targeting, sequential nano-catalytic therapy, and dual-imaging guidance/monitoring.

To Enhance Mucus Penetration and Lung Absorption of Drug by Inhalable Nanocrystals-In-Microparticles.

To effectively achieve the pulmonary delivery for curcumin (CN), novel inhalable mucus-penetrating nanocrystal-based microparticles (INMP) were designed. The D-Tocopherol acid polyethylene glycol 1000 succinate (TPGS) modified CN nanocrystals (CN-NS@TPGS) were prepared by high pressure homogenization and further converted into nanocrystal-based microparticles (CN-INMP@TPGS) using spray-drying. It was demonstrated that CN-NS@TPGS exhibited little interaction with the negatively charged mucin due to a strong electrostatic repulsion effect and PEG hydrophilic chain, and exhibited a much higher penetration ability across the mucus layer compared with poloxamer 407 modified CN-NS (CN-NS@P407) and tween 80 modified CN-NS (CN-NS@TW80). The aerodynamic results demonstrated that the CN-INMP with 10% TPGS acting as the stabilizer presented a high FPF value, indicating excellent deposition in the lung after inhalation administration. Additionally, in vivo bioavailability studies indicated that the AUC(0-t) of CN-INMP@TPGS (2413.18 ± 432.41 µg/L h) were 1.497- and 3.32-fold larger compared with those of CN-INMP@TW80 (1612.35 ± 261.35 µg/L h) and CN-INMP@P407 (3.103 ± 196.81 µg/L h), respectively. These results indicated that the CN-INMP@TPGS were absorbed rapidly after pulmonary administration and resulted in increased systemic absorption. Therefore, the inhalable CN-INMP could significantly improve the bioavailability of CN after inhalation administration. The developed mucus-penetrating nanocrystals-in-microparticles might be regarded as a promising formulation strategy for the pulmonary administration of poorly soluble drugs.

Nanocrystals based pulmonary inhalation delivery system: advance and challenge.

Pulmonary inhalation administration is an ideal approach to locally treat lung disease and to achieve systemic administration for other diseases. However, the complex nature of the structural characteristics of the lungs often results in the difficulty in the development of lung inhalation preparations. Nanocrystals technology provides a potential formulation strategy for the pulmonary delivery of poorly soluble drugs, owing to the decreased particle size of drug, which is a potential approach to overcome the physiological barrier existing in the lungs and significantly increased bioavailability of drugs. The pulmonary inhalation administration has attracted considerable attentions in recent years. This review discusses the barriers for pulmonary drug delivery and the recent advance of the nanocrystals in pulmonary inhalation delivery. The presence of nanocrystals opens up new prospects for the development of novel pulmonary delivery system. The particle size control, physical instability, potential cytotoxicity, and clearance mechanism of inhaled nanocrystals based formulations are the major considerations in formulation development.

Proteiniphilum propionicum sp. nov., a novel member of the phylum Bacteroidota isolated from pit clay used to produce Chinese liquor.

A novel, Gram-stain-negative, rod-shaped, strictly anaerobic bacterium of genus Proteiniphilum of the phylum Bacteroidota, named strain JNU-WLY501T, was isolated from pit clay used to produce strong aroma-type liquor in PR China. The genomic DNA G+C content and genome size of JNU-WLY501T were 41.4 % and 3.9 Mbp, respectively. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that JNU-WLY501T was closely related to Proteiniphilum acetatigenes DSM 18083T (95.7 %) and Proteiniphilum saccharofermentans M3/6T (94.9 %). The pairwise average nucleotide identity based on blast and average amino acid identity values of JNU-WLY501T compared with Proteiniphilum saccharofermentans M3/6T were 73.6 and 77.3 %, respectively, which both were lower than the threshold values for bacterial species delineation. The strain grew at 20-40 °C, with optimum growth at 37 °C. The pH range for growth was 5.4-9.1, with optimum growth at pH 7.5. The sodium chloride range for growth was 0.0-4.0 %, with optimum growth at 0 %. The strain did not use glucose, maltose, fructose or starch. Yeast extract, tryptone and peptone supported the growth of JNU-WLY501T, and the main fermentation products were acetate and propionate. The predominant cellular fatty acids (>5 %) of JNU-WLY501T were anteiso-C15 : 0 (30.6 %), anteiso-C17 : 0 (26.1 %), C16 : 0 (7.7 %), iso-C16 : 0 (5.0 %) and iso-C17 : 0 (5.0 %). The respiratory quinone of JNU-WLY501T was MK-5. On the basis of the morphological, physiological, biochemical, chemotaxonomic, genotypic and phylogenetic results, JNU-WLY501T represents a novel species of the genus Proteiniphilum, for which the name Proteiniphilum propionicum sp. nov. is proposed. The type strain is JNU-WLY501T (=GDMCC 1.2686T=JCM 34753T).

Efficient preparation of (R)-2-(2,5-difluorophenyl)pyrrolidine via a recycle process of resolution.

An efficient preparation of (R)-2-(2,5-difluorophenyl)pyrrolidine ((R)-1) from the racemate based on a recycle process of resolution/racemization was described. In the process, the desired (R)-1 was obtained by resolution with D-malic acid in 95% EtOH. Meanwhile, the undesired (S)-1 could be racemized in the presence of potassium hydroxide in DMSO. After three times of recycle process, the desired freebase (R)-1 was obtained in a yield of 61.7% with excellent ee (98.4%).

Physiological and transcriptomic changes of zebrafish (Danio rerio) embryos-larvae in response to 2-MIB exposure.

2-Methylisoborneol (2-MIB), a natural odorous substance, is widely distributed in water environment, but there is a paucity of information concerning its systemic toxicity. Herein, we investigated the effects of 2-MIB exposure on developmental parameters, locomotive behavior, oxidative stress, apoptosis and transcriptome of zebrafish. Zebrafish embryos exposed to different concentrations (0, 0.5, 5 and 42.8 µg/L) of 2-MIB showed no changes in mortality, hatchability, and malformation rate, but the body length of zebrafish larvae was significantly increased in a dose-dependent manner, and accompanied by the changes of growth hormone/insulin-like growth factor (GH/IGF) axis and the hypothalamic-pituitary-thyroid (HPT) axis genes. Moreover, the swimming activity of zebrafish larvae increased, which may be due to the increase of acetylcholinesterase (AChE) activity. Meanwhile, 2-MIB caused oxidative stress and apoptosis in zebrafish larvae by altering the NF-E2-related factor 2 (Nrf2) and mitochondrial signaling pathways, respectively. Transcriptome sequencing assay showed that the phototransduction signaling pathway was significantly enriched, and most of the genes in this pathway exhibited enhanced expression after exposure to 2-MIB. These findings provide an important reference for risk assessment and early warning to 2-MIB exposure.

Adaptability of a Caproate-Producing Bacterium Contributes to Its Dominance in an Anaerobic Fermentation System.

The transformation of diverse feedstocks into medium-chain fatty acids (MCFAs) by mixed cultures is a promising biorefinery route because of the high value of MCFAs. A particular concern is how to maintain the microbial consortia in mixed cultures to achieve stable MCFA production. The Chinese strong aroma-type liquor (Baijiu) fermentation system continually produces caproic acid for decades through a spontaneous inoculation of anaerobes from pit mud into fermented grains. Therefore, illuminating the dominant caproate-producing bacterium (CPB) in pit mud and how the CPB is sustained in the spontaneous fermentation system will help to reveal the microbiological mechanisms of stable caproate production. Here, we examined pit mud samples across four Chinese strong aroma-type Baijiu-producing areas and found that a caproate-producing Caproicibacterium sp. was widely distributed in these distilleries, with relative abundance ranging from 1.4 to 35.5% and an average abundance of 11.4%. Through controlling carbon source availability, we obtained different simplified caproate-producing consortia and found that the growth advantage of Caproicibacterium sp. was highly dependent on glucose. Then, two strains, named Caproicibacterium sp. strain LBM19010 and Caproicibacterium sp. strain JNU-WLY1368, were isolated from pit mud of two regions. The metabolic versatility of this species utilizing starch, maltose, glucose, and lactate reflected its adaptability to the fermentation environment where these carbon sources coexist. The simultaneous utilization of glucose and lactate contributed to the balance between cell growth and pH homeostasis. This study reveals that multiple adaptation strategies employed by the predominant CPB promotes its stability and dominance in a saccharide- and lactate-rich anaerobic habitat. IMPORTANCE The Chinese strong aroma-type liquor (Baijiu) fermentation environment is a typical medium-chain fatty acid-producing system with complex nutrients. Although several studies have revealed the correlation between microbial community composition and abiotic factors, the adaptation mechanisms of dominant species to abiotic environment are still unknown in this special anaerobic habitat. This study identified the predominant CPB in Chinese strong aroma-type Baijiu fermentation system. Metabolic versatility and flexibility of the dominant CPB with a small-size genome indicated that this bacterium can effectively exploit available carbon and nitrogen sources, which could be a key factor to promote its ecological success in a multispecies environment. The understanding of growth and metabolic features of the CPB responsible for its dominance in microbial community will not only contribute to the improvement of Chinese strong aroma-type Baijiu production but also expand its potential industrial applications in caproate production.