Soil erosion is a major drive for nano & micro-plastics to enter riverine systems from cultivated land.

Nano and micro-plastics (NMPs, particles diameter <5 mm), as emerging contaminants, have become a major concern in the aquatic environment because of their adverse consequences to aquatic life and potentially human health. Implementing mitigation strategies requires quantifying NMPs mass emissions and understanding their sources and transport pathways from land to riverine systems. Herein, to access NMPs mass input from agricultural soil to riverine system via water-driven soil erosion, we have collected soil samples from 120 cultivated land in nine drainage basins across China in 2021 and quantified the residues of six common types of plastic, including polyvinyl chloride (PVC), polymethyl methacrylate (PMMA), polypropylene (PP), polyethylene (PE), polycarbonate (PC), and polystyrene (PS). NMPs (Σ6plastics) were detected in all samples at concentrations between 3.6 and 816.6 µg/g dry weight (median, 63.3 µg/g) by thermal desorption/pyrolysis-gas chromatography-mass spectrometry. Then, based on the Revised Universal Soil Loss Equation model, we estimated that about 22,700 tonnes of NMPs may enter the Chinese riverine system in 2020 due to agricultural water-driven soil erosion, which occurs primarily from May to September. Our result suggested that over 90% of the riverine NMPs related to agricultural soil erosion in China are attributed to 36.5% of the country's total cultivated land, mainly distributed in the Yangtze River Basin, Southwest Basin, and Pearl River Basin. The migration of NMPs due to water-driven soil erosion cannot be ignored, and erosion management strategies may contribute to alleviating plastic pollution issues in aquatic systems.

Electrostatic interactions between rough dielectric particles.

From colloid suspension to particle aggregation in protoplanetary formation, electrostatic attraction and repulsion between particles is a key mechanism behind the aggregation and clustering of particles. Although most studies have focused on canonical spherical particles, it remains unclear how nonspherical and rough dielectric particles interact and whether the complicated interplay between roughness and charge distribution affects their force couplings. Here a boundary-element method model was leveraged to study electrostatic interactions between charged dielectric particles with modular, axisymmetric surface features. Charge accumulation at convex surface asperities decreases the strength of electrostatic interactions between particles, and the sensitivity of the electrostatic force to the particle surface roughness and orientation is especially apparent at small particle separations. Surface interactions between the particle near-contact regions were isolated to determine the degree that near-contact interactions dictate the relationship between the net electrostatic force and the particle roughness and orientation. A correction factor ΔF is introduced to recover higher order dielectric effects from a low order analytical model. Finally, implications of surface charge asymmetries produced for different particle orientations and surface roughnesses on the long-standing problem of triboelectrification are discussed.

Drug-induced interstitial lung disease: a real-world pharmacovigilance study of the FDA Adverse Event Reporting System from 2004 to 2021.

Background: Drug-induced interstitial lung disease (DILD) is an increasingly common cause of morbidity and mortality. However, due to the lack of specificity, DILD detection remains an unsolved public health challenge. Objectives: For the first time, we aimed to examine DILD reports submitted to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to identify demographic characteristics and top drugs associated with DILD at a group level (including age, sex, drug class, and country stratification) and individual drug level. Design: A retrospective analysis of the FAERS database was examined by disproportionality analysis. Methods: We reviewed the FAERS database from 2004 to 2021, using search terms 'interstitial lung disease' and sorting cases by generic drug name. The reporting odds ratio, proportional reporting ratio, and Bayesian confidence propagation neural network were calculated as the measure of strength of association. Results: There were 32,821 DILD reports in the FAERS. After excluding reports without age, sex, or country data according to the specific measurement, the median age of patients was 68 (interquartile range: 59), 54.77% were male, and 46.00% of reports came from Japan. The top drug classes related to DILD in the FAERS were antineoplastic, followed by cardiovascular and antirheumatic agents, in varying order in different sexes. Fam-trastuzumab deruxtecan-nxki, ramucirumab, and eribulin were the top three drugs with the highest strength of association. We also found some drugs without DILD in the labels, such as amiodarone, temsirolimus, and ursodiol. There are significant differences in DILD reports in various countries. For example, the United States and France reported more cardiovascular agents, whereas Canada reported more antirheumatic agents. Conclusion: We found the top drugs and drug classes that were associated with DILD in the FAERS, which provides a real-world window for different ages, sexes, and countries to formulate precise pharmacovigilance policies.

A study on drug-induced interstitial lung disease Introduction: The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database is the largest public database for spontaneous reporting of adverse events, any undesirable experiences that occur while taking a medication. The FDA designed the FAERS database to allow them to track the safety of drugs once they are released on the market. This study aims to explore drug-induced interstitial lung disease (DILD) reporting trends, demographic characteristics, most commonly reported drugs, and high strength of association drugs using the FAERS database. Methods: We retrieved the term 'interstitial lung disease' to extract DILD reports in the FAERS database from 2004 to 2021. Then, we not only counted basic patient information, including age, gender, and reporting country, but also analyzed the drug class, the reporting frequency of drug, and the degree of relevance. Results: We identified a total of 32,821 DILD reports. DILD reports had a persistent increase from 2004 to 2021. The top three drug classes related to DILD in the FAERS were antineoplastic, cardiovascular and antirheumatic agents. The top three reported drugs associated with DILD were methotrexate, doxorubicin, and pembrolizumab. The top three drugs with the highest strength of association were fam-trastuzumab deruxtecan-nxki, ramucirumab, and eribulin. Various countries have significant differences in drugs related to DILD. Conclusion: By analyzing data from the FAERS database, we identified the top drugs, drug classes, and some unexpected drugs without DILD in the labels. Our findings provide additional insight into DILD to inform clinicians to enhance monitor related to drugs of potential importance.

Novel Multiresistant Osmotin-like Protein from Sweetpotato as a Promising Biofungicide to Control Ceratocystis fimbriata by Destroying Spores through Accumulation of Reactive Oxygen Species.

Osmotin-like proteins (OLPs) play an important role in host-plant defense. In this study, a novel multiresistant OLP (IbOLP1) was screened from sweetpotato (Ipomoea batatas) with a molecular weight of 26.3 kDa. The expression level of IbOLP1 was significantly higher in resistant cultivars than susceptible ones after inoculation with Ceratocystis fimbriata, which causes black rot disease in sweetpotato. The expression of IbOLP1 in Pichia pastoris led to the lysis of yeast cells themselves. The recombinant IbOLP1 displayed antifungal, antibacterial, and antinematode activity and stability. IbOLP1 could restrain the mycelial growth and lyse spores of C. fimbriata, distinctly reducing the incidence of black rot in sweetpotato. The IbOLP1 can trigger the apoptosis of black rot spores by elevating the intracellular levels of reactive oxygen species. Collectively, these findings suggest that IbOLP1 can be used to develop natural antimicrobial resources instead of chemical agents and generate new, disease-resistant germplasm.

Nicotinamide mononucleotide as a therapeutic agent to alleviate multi-organ failure in sepsis.

BACKGROUND: Sepsis-caused multi-organ failure remains the major cause of morbidity and mortality in intensive care units with limited therapeutics. Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD+), has been recently reported to be protective in sepsis; however, its therapeutic effects remain to be determined. This study sought to investigate the therapeutic effects of NMN in septic organ failure and its underlying mechanisms. METHODS: Sepsis was induced by feces-injection-in-peritoneum in mice. NMN was given after an hour of sepsis onset. Cultured neutrophils, macrophages and endothelial cells were incubated with various agents. RESULTS: We demonstrate that administration of NMN elevated NAD+ levels and reduced serum lactate levels, oxidative stress, inflammation, and caspase-3 activity in multiple organs of septic mice, which correlated with the attenuation of heart dysfunction, pulmonary microvascular permeability, liver injury, and kidney dysfunction, leading to lower mortality. The therapeutic effects of NMN were associated with lower bacterial burden in blood, and less ROS production in septic mice. NMN improved bacterial phagocytosis and bactericidal activity of macrophages and neutrophils while reducing the lipopolysaccharides-induced inflammatory response of macrophages. In cultured endothelial cells, NMN mitigated mitochondrial dysfunction, inflammation, apoptosis, and barrier dysfunction induced by septic conditions, all of which were offset by SIRT3 inhibition. CONCLUSION: NAD+ repletion with NMN prevents mitochondrial dysfunction and restrains bacterial dissemination while limiting inflammatory damage through SIRT3 signaling in sepsis. Thus, NMN may represent a therapeutic option for sepsis.

Dual-site beta tACS over rIFG and M1 enhances response inhibition: A parallel multiple control and replication study

Response inhibition is a core component of cognitive control. Past electrophysiology and neuroimaging studies have identified beta oscillations and inhibitory control cortical regions correlated with response inhibition, including the right inferior frontal gyrus (rIFG) and primary motor cortex (M1). Hence, increasing beta activity in multiple brain regions is a potential way to enhance response inhibition. Here, a novel dual-site transcranial alternating current stimulation (tACS) method was used to modulate beta activity over the rIFG-M1 network in a sample of 115 (excluding 2 participants) with multiple control groups and a replicated experimental design. In Experiment 1, 70 healthy participants were randomly assigned to three dual-site beta-tACS groups, including in-phase, anti-phase or sham stimulation. During and after stimulation, participants were required to complete the stop-signal task, and electroencephalography (EEG) was collected before and after stimulation. The Barratt Impulsiveness Scale was completed before the experiment to evaluate participants' impulsiveness. In addition, we conducted an active control experiment with a sample size of 20 to exclude the potential effects of the dual-site tACS “return” electrode. To validate the behavioural findings of Experiment 1, 25 healthy participants took part in Experiment 2 and were randomized into two groups, including in-phase and sham stimulation groups. We found that compared to the sham group, in-phase but not anti-phase beta-tACS significantly improved both response inhibition performance and beta synchronization of the inhibitory control network in Experiment 1. Furthermore, the increased beta synchronization was correlated with enhanced response inhibition. In an independent sample of Experiment 2, the enhanced response inhibition performance observed in the in-phase group was replicated. (AU)

Opportunities and challenges of pharmacovigilance in special populations: a narrative review of the literature.

The relatively new discipline of pharmacovigilance (PV) aims to monitor the safety of drugs throughout their evolution and is essential to discovering new drug risks. Due to their specific and complex physiology, children, pregnant women, and elderly adults are more prone to adverse drug reactions (ADRs). Additionally, the lack of clinical trial data exacerbates the challenges faced with pharmacotherapy in these populations. Elderly patients tend to have multiple comorbidities often requiring more extensive medication, which adds additional challenges for healthcare professionals (HCPs) in delivering safe and effective pharmacotherapy. Clinical trials often have inherent limitations, including insufficient sample size and limited duration of research; as some ADRs are attributed to long-term use of a drug, these may go undetected during the course of the trial. Therefore, the implementation of PV is key to insuring the safe and effective use of drugs in special populations. We conducted a thorough review of the scientific literature on PV systems across the European Union, the United States, and China. Our review focused on basic physiological characteristics, drug use, and PV for specific populations (children, pregnant women, and the elderly). This article aims to provide a reference for the development of follow-up policies and improvement of existing policies as well as provide insight into drug safety with respect to patients of special populations.

Pharmacovigilance (PV) in special populations: opportunities and challenges Why is it important to implement PV in special populations? Due to the particularity of physiological functions, the special population (children, pregnant women, and the elderly) are more susceptible to adverse drug reactions (ADRs) and have more drug safety problems. The implementation of PV is helpful for the detection of safety risks throughout the life cycle of drugs, so that healthcare professionals (HCPs) can take early measures to reduce the drug use risks of patients. What are the problems to implement PV for special populations? Many countries have implemented a PV system. However, PV policies and systems for the special population are not complete in various countries, or no independent PV system for the special population has been set up. What does this article add to our knowledge? This article discusses the PV systems of the European Union, the United States, and China with special focus on basic physiological characteristics, use of drugs, and the implementation of PV with respect to children, pregnant women, and the elderly. Focus on these problems are of great importance for formulating a more complete drug management scheme in the special population and can provide a reference for the development of follow-up policies and improvement of existing policies.

The complete chloroplast genome of Allium wallichii Kunth (Amaryllidaceae).

Allium wallichii Kunth is a herb species with potentially extensive applications because of its edible, ornamental, and pharmaceutical values. The structural characteristics and phylogenetic relationships of its chloroplast genome were determined here for the first time. The complete cp genome was found to be 152,496 bp long, with a GC content of 37.04%. It consists of four distinct regions: a large single copy (LSC) region of 82,510 bp, a small single copy (SSC) region of 17,460 bp, and two inverted repeat (IR) regions of 26,263 bp each. The genome encodes 129 genes, including 86 protein-coding genes, 37 tRNA genes, and six rRNA genes. Our phylogenetic analysis revealed that A. wallichii was closely related to Allium wallichii var. platyphyllum, which are included in the section Bromatorrhiza, subgenus Amerallium Traub of the genus Allium. Our report provides valuable information on the genetic diversity of Allium species.

Cost-effectiveness of serplulimab as first-line therapy for extensive-stage small cell lung cancer in China.

Objective: The ASTRUM-005 trial demonstrated that adding serplulimab to chemotherapy significantly prolonged the survival of patients with extensive-stage small cell lung cancer (SCLC), but also increased the risk of adverse events. Given the high cost of serplulimab compared to chemotherapy, this study aimed to evaluate the cost-effectiveness of serplulimab plus chemotherapy as a first-line treatment for extensive-stage SCLC from the perspective of China's healthcare system. Methods: A Markov model was developed to simulate the disease process of extensive-stage SCLC and estimate the health outcomes and direct medical costs of patients. Scenario analyses, univariate sensitivity analyses, and probabilistic sensitivity analyses were conducted to explore the impact of different parameters on model uncertainty. The primary model outcomes included costs, life-years (LYs), quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). Results: Compared to placebo plus chemotherapy, serplulimab plus chemotherapy resulted in an additional 0.25 life-years and 0.15 QALYs, but also increased costs by $26,402, resulting in an ICER of 179,161 USD/QALY. Sensitivity analysis showed that the ICER was most sensitive to the cost of serplulimab, and the probability that serplulimab was cost-effective when added to chemotherapy was only 0 at the willingness-to-pay threshold of 37,423 USD/QALY. Scenario analysis revealed that price discounts on serplulimab could increase its probability of being cost-effective. Conclusion: Serplulimab plus chemotherapy is not a cost-effective strategy for first-line treatment of extensive-stage SCLC in China. Price discounts on serplulimab can enhance its cost-effectiveness.

Scaling laws of plume-induced granular cratering.

Extraterrestrial landing often requires firing a high-speed plume towards a planetary surface, and the resulting gas-granular interactions pose potential hazards to the lander. To investigate these jet-induced cratering dynamics, an experiment campaign covering a range of gas and granular properties relevant to the lunar and Martian environments was conducted in a large-scale vacuum chamber. Despite the variations in jet Mach number, mass flow rate, and composition of the granular phase investigated in this work, the observed time evolution of crater depth displays a consistent transition from an early-stage linear to a late-stage sublinear growth. To explain these scaling relations, a model that relates the kinetic energy gained by the particles per unit time to the power of the impinging jet is introduced. From this model, erosion rates and the critical depth at which the transition occurs can be extracted, and they are shown to depend on the gas impingement pressure, which was varied by changing ambient pressure, jet Mach number, mass flow rate, and nozzle height above the surface. These results highlight key mechanisms at work in the dynamics of plume-induced cratering and help to develop an understanding of optimal rocket engine firing times for future landings.

Dual-site beta tACS over rIFG and M1 enhances response inhibition: A parallel multiple control and replication study.

Response inhibition is a core component of cognitive control. Past electrophysiology and neuroimaging studies have identified beta oscillations and inhibitory control cortical regions correlated with response inhibition, including the right inferior frontal gyrus (rIFG) and primary motor cortex (M1). Hence, increasing beta activity in multiple brain regions is a potential way to enhance response inhibition. Here, a novel dual-site transcranial alternating current stimulation (tACS) method was used to modulate beta activity over the rIFG-M1 network in a sample of 115 (excluding 2 participants) with multiple control groups and a replicated experimental design. In Experiment 1, 70 healthy participants were randomly assigned to three dual-site beta-tACS groups, including in-phase, anti-phase or sham stimulation. During and after stimulation, participants were required to complete the stop-signal task, and electroencephalography (EEG) was collected before and after stimulation. The Barratt Impulsiveness Scale was completed before the experiment to evaluate participants' impulsiveness. In addition, we conducted an active control experiment with a sample size of 20 to exclude the potential effects of the dual-site tACS "return" electrode. To validate the behavioural findings of Experiment 1, 25 healthy participants took part in Experiment 2 and were randomized into two groups, including in-phase and sham stimulation groups. We found that compared to the sham group, in-phase but not anti-phase beta-tACS significantly improved both response inhibition performance and beta synchronization of the inhibitory control network in Experiment 1. Furthermore, the increased beta synchronization was correlated with enhanced response inhibition. In an independent sample of Experiment 2, the enhanced response inhibition performance observed in the in-phase group was replicated. After combining the data from the above two experiments, the time dynamics analysis revealed that the in-phase beta-tACS effect occurred in the post-stimulation period but not the stimulation period. The state-dependence analysis showed that individuals with poorer baseline response inhibition or higher attentional impulsiveness had greater improvement in response inhibition for the in-phase group. These findings strongly support that response inhibition in healthy adults can be improved by in-phase dual-site beta-tACS of the rIFG-M1 network, and provide a new potential treatment targets of synchronized cortical network activity for patients with clinically deficient response inhibition.

VEGF signaling governs the initiation of biliary-mediated liver regeneration through the PI3K-mTORC1 axis.

Biliary epithelial cells (BECs) are a potential source to repair the damaged liver when hepatocyte proliferation is compromised. Promotion of BEC-to-hepatocyte transdifferentiation could be beneficial to the clinical therapeutics of patients with end-stage liver diseases. However, mechanisms underlying the initiation of BEC transdifferentiation remain largely unknown. Here, we show that upon extreme hepatocyte injury, vegfaa and vegfr2/kdrl are notably induced in hepatic stellate cells and BECs, respectively. Pharmacological and genetic inactivation of vascular endothelial growth factor (VEGF) signaling would disrupt BEC dedifferentiation and proliferation, thus restraining hepatocyte regeneration. Mechanically, VEGF signaling regulates the activation of the PI3K-mammalian target of rapamycin complex 1 (mTORC1) axis, which is essential for BEC-to-hepatocyte transdifferentiation. In mice, VEGF signaling exerts conserved roles in oval cell activation and BEC-to-hepatocyte differentiation. Taken together, this study shows VEGF signaling as an initiator of biliary-mediated liver regeneration through activating the PI3K-mTORC1 axis. Modulation of VEGF signaling in BECs could be a therapeutic approach for patients with end-stage liver diseases.

The applications of functional materials-based nano-formulations in the prevention, diagnosis and treatment of chronic inflammation-related diseases.

Chronic inflammation, in general, refers to systemic immune abnormalities most often caused by the environment or lifestyle, which is the basis for various skin diseases, autoimmune diseases, cardiovascular diseases, liver diseases, digestive diseases, cancer, and so on. Therapeutic strategies have focused on immunosuppression and anti-inflammation, but conventional approaches have been poor in enhancing the substantive therapeutic effect of drugs. Nanomaterials continue to attract attention for their high flexibility, durability and simplicity of preparation, as well as high profitability. Nanotechnology is used in various areas of clinical medicine, such as medical diagnosis, monitoring and treatment. However, some related problems cannot be ignored, including various cytotoxic and worsening inflammation caused by the nanomaterials themselves. This paper provides an overview of functional nanomaterial formulations for the prevention, diagnosis and treatment of chronic inflammation-related diseases, with the intention of providing some reference for the enhancement and optimization of existing therapeutic approaches.

Tmed10 deficiency results in impaired exocrine pancreatic differentiation in zebrafish larvae.

Transmembrane p24 trafficking protein 10 (TMED10) is a conserved vesicle trafficking protein. It is dysregulated in Alzheimer disease and plays a pivotal role in the pathogenesis of Alzheimer disease. In addition to the brain, TMED10 is highly expressed in the exocrine pancreas; however, its biological functions and underlying mechanisms remain largely unknown. We studied reduced Tmed10 in zebrafish embryos by morpholino oligonucleotide knockdown and CRISPR-Cas9 mutagenesis. Tmed10-deficient embryos showed extensive loss of acinar mass and impaired acinar differentiation. TMED10 has been reported to have an inhibitory effect on γ-secretase. As one of the substrates of γ-secretase, membrane-bound ß-catenin was significantly reduced in Tmed10-deficient embryos. Increased γ-secretase activity in wild-type embryos resulted in a phenotype similar to that of tmed10 mutants. And the mutant phenotype could be rescued by treatment with the γ-secretase inhibitor, N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-s-phenylglycinet-butyl ester (DAPT). In addition, the reduced membrane-bound ß-catenin was accompanied with up-regulated ß-catenin target genes in Tmed10-deficient embryos. Overexpression of ß-catenin signaling inhibitor Dickkopf-1 (DKK-1) could rescue the exocrine pancreas defects. Taken together, our study reveals that Tmed10 regulates exocrine pancreatic differentiation through γ-secretase. Reduced membrane-bound ß-catenin, accompanied with hyperactivation of ß-catenin signaling, is an important cause of exocrine pancreas defects in Tmed10-deficient embryos. Our study reaffirms the importance of appropriate ß-catenin signaling in exocrine pancreas development. These findings may provide a theoretical basis for the development of treatment strategies for TMED10-related diseases.

Association of dietary total antioxidant capacity with all-cause and cardiovascular mortality in patients with chronic kidney disease: based on two retrospective cohort studies of NHANES.

BACKGROUND: The relationship between dietary total antioxidant capacity (DTAC) and death risk among CKD populations remains unclear. METHODS: Based on vitamin C equivalent antioxidant capacity (VCEAC) and the component dietary antioxidant index (CDAI) indices, we analyzed two cohorts to investigate the association of DTAC with all-cause and CVD mortality in CKD patients using data from National Health and Nutrition Examination Survey (2007-2018). VCEAC (n = 6330) and CDAI (n = 6300) cohorts with mortality follow-up data available through 2018 were included. Cox models with restricted cubic splines was used to model the nonlinear association between VCEAC/CDAI and outcomes in CKD patients. RESULTS: Our results showed L-shaped associations of DTAC with all-cause mortality among individuals with CKD stages 1-2 in both cohorts. Compared to the lowest quartile, higher dietary total antioxidant intake was associated with lower all-cause mortality risks among CKD stages 1-2 after adjustment for covariates, with HRs (95%CI) of 1.00, 0.91 (0.71,1.17), 0.69 (0.53,0.90), and 0.70 (0.54,0.91) in VCEAC, and similar respective estimate trends in CDAI. After sensitivity and subgroup analyses, there were no benefits for patients with stage 3-5 CKD or albuminuria. Mediation analysis revealed that the proportions mediated in both cohorts were less consistent. CONCLUSIONS: Moderate dietary total antioxidants intake has potential benefits for early-stage CKD patients. However, further evidence is needed to confirm whether patients with worsening CKD can benefit in the long term.

Mutation in crrB encoding a sensor kinase increases expression of the RND-type multidrug efflux pump KexD in Klebsiella pneumoniae.

BACKGROUND: RND-type multidrug efflux systems in Gram-negative bacteria protect them against antimicrobial agents. Gram-negative bacteria generally possess several genes which encode such efflux pumps, but these pumps sometimes fail to show expression. Generally, some multidrug efflux pumps are silent or expressed only at low levels. However, genome mutations often increase the expression of such genes, conferring the bacteria with multidrug-resistant phenotypes. We previously reported mutants with increased expression of the multidrug efflux pump KexD. We aimed to identify the cause of KexD overexpression in our isolates. Furthermore, we also examined the colistin resistant levels in our mutants. METHODS: A transposon (Tn) was inserted into the genome of Klebsiella pneumoniae Em16-1, a KexD-overexpressing mutant, to identify the gene(s) responsible for KexD overexpression. RESULTS: Thirty-two strains with decreased kexD expression after Tn insertion were isolated. In 12 of these 32 strains, Tn was identified in crrB, which encodes a sensor kinase of a two-component regulatory system. DNA sequencing of crrB in Em16-1 showed that the 452nd cytosine on crrB was replaced by thymine, and this mutation changed the 151st proline into leucine. The same mutation was found in all other KexD-overexpressing mutants. The expression of crrA increased in the mutant overexpressing kexD, and the strains in which crrA was complemented by a plasmid showed elevated expression of kexD and crrB from the genome. The complementation of the mutant-type crrB also increased the expression of kexD and crrA from the genome, but the complementation of the wild-type crrB did not. Deletion of crrB decreased antibiotic resistance levels and KexD expression. CrrB was reported as a factor of colistin resistance, and the colistin resistance of our strains was tested. However, our mutants and strains carrying kexD on a plasmid did not show increased colistin resistance. CONCLUSION: Mutation in crrB is important for KexD overexpression. Increased CrrA may also be associated with KexD overexpression.

Extensive jejunal injury is repaired by migration and transdifferentiation of ileal enterocytes in zebrafish.

A major cause of intestinal failure (IF) is intestinal epithelium necrosis and massive loss of enterocytes, especially in the jejunum, the major intestinal segment in charge of nutrient absorption. However, mechanisms underlying jejunal epithelial regeneration after extensive loss of enterocytes remain elusive. Here, we apply a genetic ablation system to induce extensive damage to jejunal enterocytes in zebrafish, mimicking the jejunal epithelium necrosis that causes IF. In response to injury, proliferation and filopodia/lamellipodia drive anterior migration of the ileal enterocytes into the injured jejunum. The migrated fabp6+ ileal enterocytes transdifferentiate into fabp2+ jejunal enterocytes to fulfill the regeneration, consisting of dedifferentiation to precursor status followed by redifferentiation. The dedifferentiation is activated by the IL1ß-NFκB axis, whose agonist promotes regeneration. Extensive jejunal epithelial damage is repaired by the migration and transdifferentiation of ileal enterocytes, revealing an intersegmental migration mechanism of intestinal regeneration and providing potential therapeutic targets for IF caused by jejunal epithelium necrosis.

The MRN complex maintains the biliary-derived hepatocytes in liver regeneration through ATR-Chk1 pathway.

When the proliferation of residual hepatocytes is prohibited, biliary epithelial cells (BECs) transdifferentiate into nascent hepatocytes to accomplish liver regeneration. Despite significant interest in transdifferentiation, little is known about the maintenance of nascent hepatocytes in post-injured environments. Here, we perform an N-ethyl-N-nitrosourea (ENU) forward genetic screen and identify a mutant containing a nonsense mutation in the gene nibrin (nbn), which encodes a component of the Mre11-Rad50-Nbn (MRN) complex that activates DNA damage response (DDR). The regenerated hepatocytes cannot be maintained and exhibit apoptosis in the mutant. Mechanistically, the nbn mutation results in the abrogation of ATR-Chk1 signaling and accumulations of DNA damage in nascent hepatocytes, which eventually induces p53-mediated apoptosis. Furthermore, loss of rad50 or mre11a shows similar phenotypes. This study reveals that the activation of DDR by the MRN complex is essential for the survival of BEC-derived hepatocytes, addressing how to maintain nascent hepatocytes in the post-injured environments.

Folding Dynamics and Its Intermittency in Turbulence.

Fluid elements deform in turbulence by stretching and folding. In this Letter, by projecting the material deformation tensor onto the largest stretching direction, we depict the dynamics of folding through the evolution of the material curvature. Results from direct numerical simulation (DNS) show that the curvature growth exhibits two regimes: first, a linear stage dominated by folding fluid elements through a persistent velocity Hessian that then transition to an exponential-growth stage driven by the stretching of already strongly bent fluid elements. This transition leads to strong curvature intermittency at later stages, which can be explained by a proposed curvature-evolution model. The link between velocity Hessian to folding provides a new way to understand the crucial steps in energy cascade and mixing in turbulence beyond the classical linear description of stretching dynamics.

Reconstructing the pressure field around swimming fish using a physics-informed neural network.

Fish detect predators, flow conditions, environments and each other through pressure signals. Lateral line ablation is often performed to understand the role of pressure sensing. In the present study, we propose a non-invasive method for reconstructing the instantaneous pressure field sensed by a fish's lateral line system from two-dimensional particle image velocimetry (PIV) measurements. The method uses a physics-informed neural network (PINN) to predict an optimized solution for the pressure field near and on the fish's body that satisfies both the Navier-Stokes equations and the constraints put forward by the PIV measurements. The method was validated using a direct numerical simulation of a swimming mackerel, Scomber scombrus, and was applied to experimental data of a turning zebrafish, Danio rerio. The results demonstrate that this method is relatively insensitive to the spatio-temporal resolution of the PIV measurements and accurately reconstructs the pressure on the fish's body.