Search

Traumatic brain injury (TBI) is an acquired insult to the brain caused by an external mechanical force, potentially resulting in temporary or permanent impairment. Microglia, the resident immune cells of the central nervous system, are activated in response to TBI, participating in tissue repair process. However, the underlying epigenetic mechanisms in microglia during TBI remain poorly understood. ARID1A (AT-Rich Interaction Domain 1 A), a pivotal subunit of the multi-protein SWI/SNF chromatin remodeling complex, has received little attention in microglia, especially in the context of brain injury. In this study, we generated a Arid1a cKO mouse line to investigate the potential roles of ARID1A in microglia in response to TBI. We found that glial scar formation was exacerbated due to increased microglial migration and a heightened inflammatory response in Arid1a cKO mice following TBI. Mechanistically, loss of ARID1A led to an up-regulation of the chemokine CCL5 in microglia upon the injury, while the CCL5-neutralizing antibody reduced migration and inflammatory response of LPS-stimulated Arid1a cKO microglia. Importantly, administration of auraptene (AUR), an inhibitor of CCL5, repressed the microglial migration and inflammatory response, as well as the glial scar formation after TBI. These findings suggest that ARID1A is critical for microglial response to injury and that AUR has a therapeutic potential for the treatment of TBI., (© 2024. The Author(s).)

Traditionally, antifungal resistance (AFR) has received much less attention compared with bacterial resistance to antibiotics. However, global changes, pandemics, and emerging new fungal infections have highlighted global health consequences of AFR. The recent report of the World Health Organisation (WHO) has identified fungal priority pathogens, and recognised AFR among the greatest global health threats. This is particularly important given the significant increase in fungal infections linked to climate change and pandemics. Environmental factors play critical roles in AFR and fungal infections, as many clinically relevant fungal pathogens and AFR originate from the environment (mainly soil). In addition, the environment serves as a potential rich source for the discovery of new antifungal agents, including mycoviruses and bacterial probiotics, which hold promise for effective therapies. In this article, we summarise the environmental pathways of AFR development and spread among high priority fungal pathogens, and propose potential mechanisms of AFR development and spread. We identify a research priority list to address key knowledge gaps in our understanding of environmental AFR. Further, we propose an integrated roadmap for predictive risk management of AFR that is critical for effective surveillance and forecasting of public health outcomes under current and future climatic conditions., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The emergence of quasiparticles in quantum many-body systems underlies the rich phenomenology in many strongly interacting materials. In the context of doped Mott insulators, magnetic polarons are quasiparticles that usually arise from an interplay between the kinetic energy of doped charge carriers and superexchange spin interactions 1-8 . However, in kinetically frustrated lattices, itinerant spin polarons-bound states of a dopant and a spin flip-have been theoretically predicted even in the absence of superexchange coupling 9-14 . Despite their important role in the theory of kinetic magnetism, a microscopic observation of these polarons is lacking. Here we directly image itinerant spin polarons in a triangular-lattice Hubbard system realized with ultracold atoms, revealing enhanced antiferromagnetic correlations in the local environment of a hole dopant. In contrast, around a charge dopant, we find ferromagnetic correlations, a manifestation of the elusive Nagaoka effect 15,16 . We study the evolution of these correlations with interactions and doping, and use higher-order correlation functions to further elucidate the relative contributions of superexchange and kinetic mechanisms. The robustness of itinerant spin polarons at high temperature paves the way for exploring potential mechanisms for hole pairing and superconductivity in frustrated systems 10,11 . Furthermore, our work provides microscopic insights into related phenomena in triangular-lattice moiré materials 17-20 ., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Propofol is a widely used anesthetic and sedative, which has been reported to exert an anti-inflammatory effect. TLR4 plays a critical role in coordinating the immuno-inflammatory response during sepsis. Whether propofol can act as an immunomodulator through regulating TLR4 is still unclear. Given its potential as a sepsis therapy, we investigated the mechanisms underlying the immunomodulatory activity of propofol., Methods: The effects of propofol on TLR4 and Rab5a (a master regulator involved in intracellular trafficking of immune factors) were investigated in macrophage (from Rab5a -/- and WT mice) following treatment with lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in vitro and in vivo, and peripheral blood monocyte from sepsis patients and healthy volunteers., Results: We showed that propofol reduced membrane TLR4 expression on macrophages in vitro and in vivo. Rab5a participated in TLR4 intracellular trafficking and both Rab5a expression and the interaction between Rab5a and TLR4 were inhibited by propofol. We also showed Rab5a upregulation in peripheral blood monocytes of septic patients, accompanied by increased TLR4 expression on the cell surface. Propofol downregulated the expression of Rab5a and TLR4 in these cells., Conclusions: We demonstrated that Rab5a regulates intracellular trafficking of TLR4 and that propofol reduces membrane TLR4 expression on macrophages by targeting Rab5a. Our study not only reveals a novel mechanism for the immunomodulatory effect of propofol but also indicates that Rab5a may be a potential therapeutic target against sepsis., (© 2024. The Author(s).)

Objective: To develop a multimodal deep-learning model for classifying Chinese medicine constitution, i.e., the balanced and unbalanced constitutions, based on inspection of tongue and face images, pulse waves from palpation, and health information from a total of 540 subjects., Methods: This study data consisted of tongue and face images, pulse waves obtained by palpation, and health information, including personal information, life habits, medical history, and current symptoms, from 540 subjects (202 males and 338 females). Convolutional neural networks, recurrent neural networks, and fully connected neural networks were used to extract deep features from the data. Feature fusion and decision fusion models were constructed for the multimodal data., Results: The optimal models for tongue and face images, pulse waves and health information were ResNet18, Gate Recurrent Unit, and entity embedding, respectively. Feature fusion was superior to decision fusion. The multimodal analysis revealed that multimodal data compensated for the loss of information from a single mode, resulting in improved classification performance., Conclusions: Multimodal data fusion can supplement single model information and improve classification performance. Our research underscores the effectiveness of multimodal deep learning technology to identify body constitution for modernizing and improving the intelligent application of Chinese medicine., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To explore the properties of gelatin-polyethylene glycol hydrogel loaded with silver nanoparticle (AgNP) Chlorella (hereinafter referred to as the composite hydrogel) and its effects on healing of infected full-thickness skin defect wounds in mice. Methods: The research was an experimental research. The simple gelatin-polyethylene glycol hydrogel (hereinafter referred to as the simple hydrogel) and the composite hydrogel were prepared, and the appearance and injectability of the two hydrogels were observed at 55 and 37 ℃, and under the irradiation of 808 nm near-infrared light, respectively. An electronic universal testing machine was employed to assess the tensile and compressive stress-strain properties of both types of hydrogels at room temperature. Additionally, the cyclic compressive stress-strain properties of the composite hydrogel were examined at 80% of the maximum compressive stress. Staphylococcus aureus or Escherichia coli solution was added to phosphate buffer solution (PBS), simple hydrogel, and composite hydrogel, respectively. The part of composite hydrogel containing Staphylococcus aureus or Escherichia coli solution was irradiated with near-infrared light for 5 minutes. After each sample was incubated for 6 h, the dilution plating method was used to detect and calculate the mortality rates of the two bacteria at 24 h of culture ( n =5). The discarded foreskin tissue was taken from a 6-year-old healthy boy admitted to the Department of Urology of the First Affiliated Hospital of Naval Medical University for circumcision. Primary human fibroblasts (HFbs) were isolated using the enzyme extraction method, routinely cultured to the 3 rd to 6 th passages for subsequent cellular experiments. Composite hydrogel extracts with final mass concentrations of 100.0, 50.0, 25.0, 12.5, and 0 mg/mL were respectively prepared and used to culture HFbs, and the cell proliferation after 24 h of culture was detected using a cell counting kit 8 ( n =3). A total of twenty 6-8 weeks old C57BL/6J female mice were utilized, and a full-thickness skin defect was surgically created on the back of each mouse. The wounds were infected with Staphylococcus aureus solution. The infected mice were divided into blank control group, simple hydrogel group, composite hydrogel group, and combined treatment group according to the random number table, and the wounds were treated with PBS, simple hydrogel, composite hydrogel, and composite hydrogel+light irradiation (under the irradiation of 808 nm near-infrared light for 5 min), respectively, with 5 mice in each group. On post injury day (PID) 0 (immediately after the first wound treatment), 3, 7, and 14, an overall assessment of wound exudation and healing were conducted, and the wound healing rates on PID 7 and 14 were calculated ( n =5). On PID 14, hematoxylin-eosin staining was performed to observe histopathological changes in the mouse wound. Results: Both simple hydrogel and composite hydrogel were in a solution state at 55 ℃ and transition to a gel state when cooling to 37 ℃. After the two hydrogels were irradiated by near-infrared light, only the composite hydrogel reheated up and returned to the solution state again with injectability. The maximum tensile stress of the composite hydrogel was up to 301.42 kPa, with a corresponding strain of 87.19%; the maximum compressive stress was up to 413.79 kPa, with a corresponding strain of 91.67%, which was similar to the tensile and compressive properties of the simple hydrogel. After 10 compression cycles, the maximum compressive stress of the composite hydrogel still reached 84.1% of the first compressive stress. After 24 h of culture, the mortality rate of Staphylococcus aureus treated with simple hydrogel was significantly higher than that treated with PBS ( P <0.05); the mortality rates of Escherichia coli and Staphylococcus aureus treated with composite hydrogel alone were significantly higher than those treated with simple hydrogel ( P <0.05); the mortality rates of Escherichia coli and Staphylococcus aureus treated with composite hydrogel+light irradiation were significantly higher than those treated with composite hydrogel alone ( P <0.05). After 24 h of culture, compared with that cultured in composite hydrogel immersion solution with final mass concentration of 0 mg/mL, the proliferation activity of HFbs cultured in composite hydrogel immersion solution with final mass concentrations of 25.0 and 50.0 mg/mL was significantly enhanced ( P <0.05), while the proliferation activity of HFbs cultured in composite hydrogel immersion solution with final mass concentration of 100 mg/mL was significantly decreased ( P <0.05). On PID 0 and 3, more purulent secretions were seen in the wounds of mice in blank control group and simple hydrogel group, while only a small amount of exudate was observed in the wounds of mice in composite hydrogel group, and no obvious infection was observed in the wounds of mice in combined treatment group. On PID 7 and 14, the wound healing rates of mice in simple hydrogel group were significantly higher than those in blank control group ( P <0.05); the wound healing rates of mice in composite hydrogel group were significantly higher than those in simple hydrogel group ( P <0.05); the wound healing rates in combined treatment group were significantly higher than those in composite hydrogel group ( P <0.05). On PID 14, the wounds of mice in blank control group exhibited a high infiltration of inflammatory cells with no new epithelial layer observed; the wounds of mice in simple hydrogel group displayed a short length of newly formed epithelium with a small amount of inflammatory cells; the wounds of mice in composite hydrogel group exhibited continuous formation of new epithelium and a large amount of immature granulation tissue; the wounds of mice in combined treatment group showed continuous epithelialization with less immature granulation tissue. Conclusions: The prepared composite hydrogel exhibits excellent thermosensitivity, photothermal properties, and injectability, as well as excellent mechanical properties, antibacterial properties, and biocompatibility, and can promote the healing of infected full-thickness skin defect wounds in mice.

Aneurysmal subarachnoid hemorrhage (aSAH) accounts for only 5 % of all stroke cases, but carries a heavy burden of morbidity and mortality. Activity regulated cytoskeleton associated protein (Arc) is an immediate early gene (IEG)-coded postsynaptic protein that is involved in synaptic plasticity. Increasing evidence and our previous studies have shown that Arc might be involved in the pathological mechanism of various neurological diseases, such as traumatic brain injury (TBI). In this study, we investigated the level of Arc in cerebrospinal fluids (CSF) of aSAH patients and its potential role in brain damage following experimental SAH model. We found that the levels of Arc in aSAH patients' CSF positively correlated with Hunt-Hess (H&H) grades. Knockdown of endogenous Arc expression by small interfere RNA (siRNA) significantly increased brain edema and oxidative stress following SAH. The results of immunostaining in brain sections showed that knockdown of Arc enhanced activation of microglia and astrocytes. In congruent, generation of inflammatory cytokines following SAH was increased by Si-Arc transfection. The results of western blot analysis showed that knockdown of Arc inhibited the expression of Sirt1 and Nrf2, which was accompanied by decreased enzymatic activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px). In addition, activation of sirtuin 1 (Sirt1) via agonist SRT2104 markedly decreased the brain damage and neuroinflammation induced by Arc knockdown. In conclusion, knockdown of endogenous Arc could aggravate brain damage and neuroinflammation following experimental SAH, and Arc levels in aSAH patients' CSF might be a potential indicator of brain damage and prognosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Protists occupy multiple trophic positions in soil food webs and significantly contribute to organic matter decomposition and biogeochemical cycling. Protists can ingest bacteria and fungi as main food sources while being subjected to predation of invertebrates, but our understanding of how bottom-up and top-down regulations structure protists in natural soil habitats is limited. Here, we disentangle the effects of trophic regulations to the diversity and structure of soil protists in natural settings across northern and eastern Australia. Bacterial and invertebrate diversity were identified as important drivers of the diversity of functional groups of protists. Moreover, the compositions of protistan taxonomic and functional groups were better predicted by bacteria and fungi, than by soil invertebrates. There were strong trophic interconnections between protists and bacteria in multiple organismic network analysis. Altogether, the study provided new evidence that, bottom-up control of bacteria played an important role in shaping the soil protist community structure, which can be derived from feeding preferences of protists on microbial prey, and their intimate relationships in soil functioning or environmental adaptation. Our findings advance our knowledge about the impacts of different trophic groups on key soil organismic communities, with implications for ecosystem functions and services., (© 2023 The Authors. Environmental Microbiology Reports published by Applied Microbiology International and John Wiley & Sons Ltd.)

Introduction: Acute lung injury (ALI) is a major cause of morbidity and mortality after intestinal ischaemia/reperfusion (I/R). The gut microbiota and its metabolic byproducts act as important modulators of the gut-lung axis. This study aimed to define the role of succinate, a key microbiota metabolite, in intestinal I/R-induced ALI progression., Methods: Gut and lung microbiota of mice subjected to intestinal I/R were analysed using 16S rRNA gene sequencing. Succinate level alterations were measured in germ-free mice or conventional mice treated with antibiotics. Succinate-induced alveolar macrophage polarisation and its effects on alveolar epithelial apoptosis were evaluated in succinate receptor 1 ( Sucnr1 )-deficient mice and in murine alveolar macrophages transfected with Sucnr1 -short interfering RNA. Succinate levels were measured in patients undergoing cardiopulmonary bypass, including intestinal I/R., Results: Succinate accumulated in lungs after intestinal I/R, and this was associated with an imbalance of succinate-producing and succinate-consuming bacteria in the gut, but not the lungs. Succinate accumulation was absent in germ-free mice and was reversed by gut microbiota depletion with antibiotics, indicating that the gut microbiota is a source of lung succinate. Moreover, succinate promoted alveolar macrophage polarisation, alveolar epithelial apoptosis and lung injury during intestinal I/R. Conversely, knockdown of Sucnr1 or blockage of SUCNR1 in vitro and in vivo reversed the effects of succinate by modulating the phosphoinositide 3-kinase-AKT/hypoxia-inducible factor-1α pathway. Plasma succinate levels significantly correlated with intestinal I/R-related lung injury after cardiopulmonary bypass., Conclusion: Gut microbiota-derived succinate exacerbates intestinal I/R-induced ALI through SUCNR1-dependent alveolar macrophage polarisation, identifying succinate as a novel target for gut-derived ALI in critically ill patients., Competing Interests: Conflict of interest: The authors declare that they have no competing interests., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

Synthetic quantum systems with interacting constituents play an important role in quantum information processing and in explaining fundamental phenomena in many-body physics. Following impressive advances in cooling and trapping techniques, ensembles of ultracold polar molecules have emerged as a promising platform that combines several advantageous properties 1-11 . These include a large set of internal states with long coherence times 12-17 and long-range, anisotropic interactions. These features could enable the exploration of intriguing phases of correlated quantum matter, such as topological superfluids 18 , quantum spin liquids 19 , fractional Chern insulators 20 and quantum magnets 21,22 . Probing correlations in these phases is crucial to understanding their properties, necessitating the development of new experimental techniques. Here we use quantum gas microscopy 23 to measure the site-resolved dynamics of quantum correlations of polar 23 Na 87 Rb molecules confined in a two-dimensional optical lattice. By using two rotational states of the molecules, we realize a spin-1/2 system with dipolar interactions between particles, producing a quantum spin-exchange model 21,22,24,25 . We study the evolution of correlations during the thermalization process of an out-of-equilibrium spin system for both spatially isotropic and anisotropic interactions. Furthermore, we examine the correlation dynamics of a spin-anisotropic Heisenberg model engineered from the native spin-exchange model by using periodic microwave pulses 26-28 . These experiments push the frontier of probing and controlling interacting systems of ultracold molecules, with prospects for exploring new regimes of quantum matter and characterizing entangled states that are useful for quantum computation 29,30 and metrology 31 ., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Rett syndrome (RTT), mainly caused by mutations in methyl-CpG binding protein 2 (MECP2), is one of the most prevalent neurodevelopmental disorders in girls. However, the underlying mechanism of MECP2 remains largely unknown and currently there is no effective treatment available for RTT., Methods: We generated MECP2-KO human embryonic stem cells (hESCs), and differentiated them into neurons and cerebral organoids to investigate phenotypes of MECP2 loss-of-function, potential therapeutic agents, and the underlying mechanism by transcriptome sequencing., Results: We found that MECP2 deletion caused reduced number of hESCs-derived neurons and simplified dendritic morphology. Moreover, MECP2-KO cortical organoids exhibited fewer neural progenitor cells and neurons at day 60. Electrophysiological recordings showed that MECP2 deletion altered synaptic activity in organoids. Transcriptome analysis of organoids identified many genes in the PI3K-AKT pathway downregulated following MECP2 deletion. Treatment with either KW-2449 or VPA, small molecules for the activation of PI3K-AKT signaling pathway, alleviated neuronal deficits and transcriptome changes in MECP2-KO human neuronal models., Conclusions: These findings suggest that KW-2449 and VPA might be promising drugs for RTT treatment., (© 2022. The Author(s).)

In this work, a series of novel 1,2,4-triazole derivatives with selenium-containing hydrophobic side chains were designed and synthesized based on the structure of lanosterol 14α-demethylase (CYP51). All compounds were characterized by HRMS, 1 H NMR and 13 C NMR. Then, their antifungal activities against eight human pathogenic fungi were evaluated in vitro by testing the minimal inhibitory concentrations. The results showed that nearly all tested compounds were found to be more potent against all tested fungal strains than control drug fluconazole. Further mechanism study demonstrated that the target compounds had fungal CYP51 inhibitory activity. Meanwhile, representative compounds revealed low cytotoxic effects toward mammalian cell lines. In addition, the docking results showed that the target compounds bound to Candida albicans CYP51 in a better pattern than fluconazole, especially in the narrow hydrophobic cleft. Overall, the novel 1,2,4-triazole derivatives with selenium-containing hydrophobic side chains can be further developed for the potential treatment of invasive fungal infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Herein, we report the design, synthesis and evaluation of a novel series of diselenide and selenide derivatives as potent antifungal agents by exploiting the hydrophobic cleft of CYP51. Among all synthesized compounds, the most potent compound B01 with low cytotoxic and hemolysis effect exhibited excellent activity against C.alb., C.gla., C.par. and C.kru., as well as selected fluconazole-resistant strains. Moreover, compound B01 could reduce the biofilm formation of the FCZ-resistant C.alb. Subsequently, metabolic stability assays using liver microsomes demonstrated that compound B01 showed good profiles of metabolic stability. With superior pharmacological profile, compound B01 was advanced into in vivo bioactivity evaluation. In a murine model of systemic C.alb. infection, compound B01 significantly reduced fungal load of kidneys. Furthermore, compound B01 revealed relatively low acute toxicity and subacute toxicity in mice. In addition, docking study performed into C.alb. CYP51, showed the binding mode between C.alb. CYP51 and compound B01. Collectively, diselenides compound B01 can be further developed for the potential treatment of invasive fungal infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Liver injury induced by intestinal ischemia/reperfusion (I/R) is accompanied by the polarization of Kupffer cells, which are specialized macrophages located in the liver. However, the causes of hepatic macrophage polarization after intestinal I/R remain unknown. This study investigated whether gut-derived exosomes contribute to the pathogenesis of liver injury triggered by intestinal I/R in a murine model and explored the underlying mechanisms. Intestinal I/R models were established by temporally clamping the superior mesenteric arteries of mice. Exosomes were isolated from the intestinal tissue of mice that underwent intestinal I/R or sham surgery according to a centrifugation-based protocol. Exosomes were co-cultured with RAW 264.7 macrophages or injected intravenously in mice. Liposomal clodronate was administered intraperitoneally to deplete the macrophages. Macrophage polarization was determined by flow cytometry, immunohistochemistry, and quantitative polymerase chain reaction. Liver injury was assessed by histological morphology and increased serum aspartate aminotransferase and alanine aminotransferase levels. Exosomes from mice intestines subjected to I/R (IR-Exo) promoted macrophage activation in vitro. Intravenous injection of IR-Exo caused hepatic M1 macrophage polarization and led to liver injury in mice. Depleting macrophages ameliorated liver injury caused by intestinal I/R or the injection of IR-Exo. Furthermore, inhibiting exosome release improved intestinal injury, liver function, and survival rates of mice subjected to intestinal I/R. Our study provides evidence that gut-derived exosomes induce liver injury after intestinal I/R by promoting hepatic M1 macrophage polarization. Inhibition of exosome secretion could be a therapeutic target for preventing hepatic impairment after intestinal I/R., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We prepare high-filling two-component arrays of tens of fermionic ^{6}Li atoms in optical tweezers, with the atoms in the ground motional state of each tweezer. Using a stroboscopic technique, we configure the arrays in various two-dimensional geometries with negligible Floquet heating. A full spin- and density-resolved readout of individual sites allows us to postselect near-zero entropy initial states for fermionic quantum simulation. We prepare a correlated state in a two-by-two tunnel-coupled Hubbard plaquette, demonstrating all the building blocks for realizing a programmable fermionic quantum simulator.

Soils harbor the most diverse naturally evolved antibiotic resistance genes (ARGs) on Earth, with implications for human health and ecosystem functioning. How ARGs evolve as soils develop over centuries, to millennia (i.e., pedogenesis), remains poorly understood, which introduces uncertainty in predictions of the dynamics of ARGs under changing environmental conditions. Here we investigated changes in the soil resistome by analyzing 16 globally distributed soil chronosequences, from centuries to millennia, spanning a wide range of ecosystem types and substrate age ranges. We show that ARG abundance and diversity decline only after millions of years of soil development as observed in very old chronosequences. Moreover, our data show increases in soil organic carbon content and microbial biomass as soil develops that were negatively correlated with the abundance and diversity of soil ARGs. This work reveals natural dynamics of soil ARGs during pedogenesis and suggests that such ecological patterns are predictable, which together advances our understanding of the environmental drivers of ARGs in terrestrial environments., (© 2022. The Author(s), under exclusive licence to International Society for Microbial Ecology.)

We use lithium-6 atoms in an optical tweezer array to realize an eight-site Fermi-Hubbard chain near half filling. We achieve single site detection by combining the tweezer array with a quantum gas microscope. By reducing disorder in the energy offsets to less than the tunneling energy, we observe Mott insulators with strong antiferromagnetic correlations. The measured spin correlations allow us to put an upper bound on the entropy of 0.26(4)k&#95;{B} per atom, comparable to the lowest entropies achieved with optical lattices. Additionally, we establish the flexibility of the tweezer platform by initializing atoms on one tweezer and observing tunneling dynamics across the array for uniform and staggered 1D geometries.

Background: Idiopathic membranous nephropathy (IMN) has a high incidence in the middle-aged and elderly population, and poses a great threat to the physical and mental health and quality of life of patients. Nephritis Rehabilitation Tablets have many potential effects, such as clearing residual toxins, tumefying the kidney and spleen, replenishing qi, and nourishing yin, and have played an important role in the treatment of a variety of kidney diseases., Aim: To investigate the efficacy and safety of Nephritis Rehabilitation Tablets combined with tacrolimus in the treatment of IMN., Methods: Eighty-four patients with IMN recruited from January 2017 to September 2020 were randomly divided into a study group ( n = 42) and a control group ( n = 42). On the basis of routine symptomatic treatment, both groups were treated with tacrolimus, and the study group was additionally treated with Nephritis Rehabilitation Tablets. Both groups were treated for 12 wk. The therapeutic effect, the levels of renal function indexes [serum creatinine (Scr), serum albumin, and 24-h urinary protein], urinary immunoglobulin (IgG4), membrane attack complex (C5b-9), and the incidence of adverse reactions were measured before and after 12 wk of treatment., Results: The total effective rate in the study group was significantly higher than that of the control group. Before treatment, there was no significant difference in Scr, serum albumin, or 24 h urinary protein between the two groups. After 12 wk of treatment, the levels of Scr and 24-h urinary protein in both groups were significantly lower and serum albumin was significantly higher than those before treatment ( P < 0.05), and the levels of Scr and 24-h urinary protein were significantly lower ( P = 0.003 and 0.000, respectively), and the level of serum albumin was significantly higher ( P = 0.00) in the study group than in the control group. Before treatment, there was no significant difference in urinary IgG4 and C5b-9 levels between the study group and the control group ( P = 0.336 and 0.438, respectively). After 12 wk of treatment, the levels of urinary IgG4 and C5b-9 in the two groups were lower than those before treatment, and the levels of urinary IgG4 and C5b-9 in the study group were significantly lower than those in the control group ( P = 0.000). There was no significant difference in the incidence of adverse reactions between the two groups ( P = 0.710)., Conclusion: Based on routine intervention, Nephritis Rehabilitation Tablets combined with tacrolimus in the treatment of IMN can effectively improve the renal function of patients and downregulate the expression of urinary IgG4 and C5b-9. In addition, they can improve the overall therapeutic effect while not increasing the risk of adverse reactions., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Termites are pivotal ecosystem engineers in tropical and subtropical habitats, where they construct massive nests ('mounds') that substantially modify soil properties and promote nutrient cycling. Yet, little is known about the roles of termite nesting activity in regulating the spread of antimicrobial resistance (AMR), one of the major Global Health challenges. Here, we conducted a large-scale (> 1500 km) investigation in northern Australia and found distinct resistome profiles in termite mounds and bulk soils. By profiling a wide spectrum of ARGs, we found that the abundance and diversity of antibiotic resistance genes (ARGs) were significantly lower in termite mounds than in bulk soils (P < 0.001). The proportion of efflux pump ARGs was significantly lower in termite mound resistome than in bulk soil resistome (P < 0.001). The differences in resistome profiles between termite mounds and bulk soils may result from the changes in microbial interactions owing to the substantial increase in pH and nutrient availability induced by termite nesting activities. These findings advance our understanding of the profile of ARGs in termite mounds, which is a crucial step to evaluate the roles of soil faunal activity in regulating soil resistome under global environmental change., (© 2021 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Understanding the current and future distributions of plant pathogens is critical to predict the plant performance and related economic benefits in the changing environment. Yet, little is known about the roles of environmental drivers in shaping the profiles of fungal plant pathogens in phyllosphere, an important habitat of microbiomes on Earth. Here, using a large-scale investigation of Eucalyptus phyllospheric microbiomes in Australia and the multiple linear regression model, we show that precipitation is the most important predictor of fungal taxonomic diversity and abundance. The abundance of fungal plant pathogens in phyllosphere exhibited a positive linear relationship with precipitation. With this empirical dataset, we constructed current and future atlases of phyllosphere plant pathogens to estimate their spatial distributions under different climate change scenarios. Our atlases indicate that the abundance of fungal plant pathogens would increase especially in the coastal regions with up to 100-fold increase compared with the current abundance. These findings advance our understanding of the distributions of fungal plant pathogens in phyllospheric microbiomes under the climate change, which can improve our ability to predict and mitigate their impacts on plant productivity and economic losses., (© 2021 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Subarachnoid hemorrhage (SAH) is a fatal disease. Within 72 h of SAH, the intracranial blood-brain barrier (BBB) is destroyed, and the nerve cells have responses such as autophagy, apoptosis, and oxidative stress. Antioxidation is an essential treatment of SAH. Astaxanthin (ATX) induces cells' antioxidant behaviors by regulating related signal pathways to reduce the damage of brain oxidative stress, inflammation, and apoptosis. Because of its easy degradability and low bioavailability, ATX is mainly encapsulated with stimulus-responsive nanocarriers to improve its stability, making it rapidly release in the brain and efficiently enter the lesion tissue. In this study, the ultrasonic cavitation agent perfluorocarbon (PFH), ATX, and fluorescent dye IR780 were loaded with polydopamine (PDA) to prepare a US triggered release nanoparticles (AUT NPs). The core-shell structure of AUT NPs formed a physical barrier to improve the bioavailability of ATX. AUT NPs have high ATX loading capacity and US responsiveness. The experimental results show that the AUT NPs have high stability in the physiological environment. Both US and pH stimuli can trigger the release. Under US, PFH breaks through the rigid shell. The structure of AUT NPs is destroyed in situ , releasing the loaded drugs into neuronal cells to realize the antioxidant and antiapoptotic effects. The in vivo experiment results show that the AUT NPs have good biosafety. They release the drugs in the brain under stimuli. The in vivo treatment results also show that AUT NPs have an excellent therapeutic effect. This approach presents an experimental basis for the establishment of Innovative SAH treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cai, Wu, Yan, He, Zhou, Zhou, Zhang and Zhang.)

With the increasing incidence of antifungal resistance, new antifungal agents having novel scaffolds hence are in an urgent need to combat infectious diseases caused by multidrug-resistant (MDR) pathogens. In this study, we reported the design, synthesis, and pharmacological evaluation of novel 1,2,3-selenadiazole analogues by scaffold hopping strategy. Preliminary results of antifungal activity demonstrated that the new class of compounds showed broad-spectrum fungistatic and fungicidal activity. Most importantly, these newly synthesized compounds can eliminate these azole-resistant fungi and inhibit the formation of C. albicans biofilm. In particular, compound S07 showed promising antifungal activity against five azole-resistant strains with MIC values ranging from 4 to 32 μg/mL. Then, further target identification and mechanistic studies indicated that representative compound S07 exert its inhibitory activity by inhibiting fungal lanosterol 14α-demethylase enzyme (CYP51). Interestingly, representative compounds showed low cytotoxicity on mammalian cell lines. In addition, the molecular docking studies elucidated the binding modes of these compounds toward CYP51. Altogether, these results suggest that compound S07 with novel skeleton is a promising CYP51 inhibitor for treatment of fungal infections., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Intestinal ischemia/reperfusion (I/R) injury is a grave condition with high morbidity and mortality. We previously confirmed that intestinal I/R induces intestinal flora disorders and changes in metabolites, but the role of different metabolites in intestinal I/R injury is currently unclear. Based on targeted metabolic sequencing, pravastatin (PA) was determined to be a metabolite of the gut microbiota. Further, intestinal I/R model mice were established through superior mesenteric artery obstruction. In addition, a co-culture model of small intestinal organoids and type II innate lymphoid cells (ILC2s) was subjected to hypoxia/reoxygenation (H/R) to simulate an intestinal I/R model. Moreover, correlation analysis between the PA level in preoperative feces of patients undergoing cardiopulmonary bypass and the indices of postoperative intestinal I/R injury was carried out. IL-33-deficient mice, ILC2-deleted mice, and anti-IL-13 neutralizing antibodies were also used to explore the potential mechanism through which PA attenuates intestinal I/R injury. We demonstrated that PA levels in the preoperative stool of patients undergoing cardiopulmonary bypass were negatively correlated with the indices of postoperative intestinal I/R injury. Furthermore, PA alleviated intestinal I/R injury and improved the survival of mice. We further showed that PA promotes IL-13 release from ILC2s by activating IL-33/ST2 signaling to attenuate intestinal I/R injury. In addition, IL-13 promoted the self-renewal of intestinal stem cells by activating Notch1 and Wnt signals. Overall, results indicated that the gut microbial metabolite PA can attenuate intestinal I/R injury by promoting the release of IL-13 from ILC2s via IL-33/ST2 signaling, revealing a novel mechanism of and therapeutic strategy for intestinal I/R injury., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Deng, Hu, Yang, Sun, Lin, Zhao, Yao, Luo, Chen, Liu, Yan, Li, Liu and Liu.)

Termites are ubiquitous insects in tropical and subtropical habitats, and some of them construct massive nests ('mounds'), which substantially promote substrate heterogeneity by altering soil properties. Yet, the role of termite nesting process in regulating the distribution and diversity of soil microbial communities remains poorly understood, which introduces uncertainty in predictions of ecosystem functions of termite mounds in a changing environment. Here, by using amplicon sequencing, we conducted a survey of 134 termite mounds across >1500 km in northern Australia and found that termite mounds significantly differed from bulk soils in the microbial diversity and community compositions. Compared with bulk soils, termite nesting process decreased the microbial diversity and the relative abundance of rare taxa. Rare taxa had a narrower habitat niche breadth than dominant taxa and might be easier to be filtered by the potential intensive microbial competition during the nesting processes. We further demonstrated that the shift in pH induced by termite nesting process was a major driver shaping the microbial community profiles in termite mounds. Together, our work provides novel evidence that termite nesting is an important process in regulating soil microbial diversity, which advances our understanding of the functioning of termite mounds., (© 2021 Society for Applied Microbiology and John Wiley & Sons Ltd.)

A series of selenium-containing miconazole derivatives were identified as potent antifungal drugs in our previous study. Representative compound A03 (MIC = 0.01 μg/mL against C.alb. 5314) proved efficacious in inhibiting the growth of fungal pathogens. However, further study showed lead compound A03 exhibited potential hemolysis, significant cytotoxic effect and unfavorable metabolic stability and was therefore modified to overcome these drawbacks. In this article, the further optimization of selenium-containing miconazole derivatives resulted in the discovery of similarly potent compound B17 (MIC = 0.02 μg/mL against C.alb. 5314), exhibiting a superior pharmacological profile with decreased rate of metabolism, cytotoxic effect and hemolysis. Furthermore, compound B17 showed fungicidal activity against Candida albicans and significant effects on the treatment of resistant Candida albicans infections. Meanwhile, compound B17 not only could reduce the ergosterol biosynthesis pathway by inhibiting CYP51, but also inhibited biofilm formation. More importantly, compound B17 also shows promising in vivo efficacy after intraperitoneal injection and the PK study of compound B17 was evaluated. In addition, molecular docking studies provide a model for the interaction between the compound B17 and the CYP51 protein. Overall, we believe that these selenium-containing miconazole compounds can be further developed for the potential treatment of fungal infections., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, “Lead optimization generates selenium-containing miconazole CYP51 inhibitors with improved pharmacological profile for the treatment of fungal infections” for possible publication in “European Journal of Medicinal Chemistry”., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

The phyllosphere and soil are two of the most important reservoirs of antibiotic resistance genes (ARGs) in terrestrial ecosystems. However, comparative studies on the biogeographic patterns of ARGs in these two habitats are lacking. Based on the construction of ARG abundance atlas across a > 4,000 km transect in eastern and northern Australia, we found contrasting biogeographic patterns of the phyllosphere and soil resistomes, which showed their distinct responses to the biotic and abiotic stresses. The similarity of ARG compositions in soil, but not in the phyllosphere, exhibited significant distance-decay patterns. ARG abundance in the phyllosphere was mainly correlated with the compositions of co-occurring bacterial, fungal and protistan communities, indicating that biotic stresses were the main drivers shaping the phyllosphere resistome. Soil ARG abundance was mainly associated with abiotic factors including mean annual temperature and precipitation as well as soil total carbon and nitrogen. Our findings demonstrated the distinct roles of biotic and abiotic factors in shaping resistomes in different environmental habitats. These findings constitute a major advance in our understanding of the current environmental resistomes and contribute to better predictions of the evolution of environmental ARGs by highlighting the importance of habitat difference in shaping environmental resistomes., (© 2021. The Author(s).)

Background: Little is known about the effect of the coronavirus disease 2019 (COVID-19) pandemic and the outbreak response measures on door-to-balloon time (D2B). This study examined both D2B and clinical outcomes of patients with STEMI undergoing primary percutaneous coronary intervention (PPCI)., Methods and results: This was a retrospective study of 303 STEMI patients who presented directly or were transferred to a tertiary hospital in Singapore for PPCI from October 2019 to March 2020. We compared the clinical outcomes of patients admitted before (BOR) and during (DOR) the COVID-19 outbreak response. The study outcomes were in-hospital death, D2B, cardiogenic shock and 30-day readmission. For direct presentations, fewer patients in the DOR group achieved D2B time <90 min compared with the BOR group (71.4% vs. 80.9%, P=0.042). This was more apparent after exclusion of non-system delay cases (DOR 81.6% vs. BOR 95.9%, P=0.006). Prevalence of both out-of-hospital cardiac arrest (9.5% vs. 1.9%, P=0.003) and acute mitral regurgitation (31.6% vs. 17.5%, P=0.006) was higher in the DOR group. Mortality was similar between groups. Multivariable regression showed that longer D2B time was an independent predictor of death (odds ratio 1.005, 95% confidence interval 1.000-1.011, P=0.029)., Conclusions: The COVID-19 pandemic and the outbreak response have had an adverse effect on PPCI service efficiency. The study reinforces the need to focus efforts on shortening D2B time, while maintaining infection control measures.

Clostridioides difficile is a key pathogen of antibiotic related diarrhea and hospital associated infection, causing several outbreaks in Europe and North Americans and resulting in severe disease burden. However, the standardized diagnostic principle and detection specifications in C . difficile infection (CDI) survey are limited in China, and the infection rate and disease burden of CDI in China are unclear. Therefore, National Institute for Communicable Disease Control and Prevention,National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, together with another 11 institutions, draft the group standard entitled "Diagnosis of Clostridium difficile infection (T/CPMA 008-2020)" of Chinese Preventive Medicine Association. Based on the principle of "legality, scientificity, advancement, and feasibility", this standard clarifies risk factors, diagnosis principles, diagnoses and differential diagnoses in order to improve the accuracy of CDI diagnosis in clinical practice, guide the surveillance for CDI, and understand the infection rate and disease burden of CDI in China .

Giant aneurysm of the posterior circulation is associated with a higher risk of rupture compared with that of the anterior circulation. Furthermore, surgical clipping and interventional embolization for giant aneurysm of the posterior circulation are more difficult and complex to perform. The present study reported on the case of a 26-year-old female who exhibited a giant spherical aneurysm of the vertebrobasilar junction (VBJ) with a maximum diameter of ~35 mm that caused cervical discomfort. In addition, the patient experienced symptoms including left-sided walking and hoarseness caused by the compression of the brainstem and the posterior cranial nerves. The risks associated with performing surgery in this area are high and the prognosis is mainly poor. The patient of the present study was treated using the Pipeline Flex device with coil embolization. As a giant aneurysm of the VBJ simultaneously affects the bilateral vertebral arteries (VAs) and basilar artery, it is a unique condition and the treatment strategy must be personalized. Based on an analysis of the hemodynamic influence on the aneurysm in the present case, the Pipeline was placed through the left VA, the coils were packed through the right VA, and finally, the right VA was proximally occluded. At 7 months after embolization, the patient's modified Rankin scale score was 1 point. Upon analysis of the hemodynamic influence on the aneurysm of the VBJ, the VA with the larger shear force on the wall of the aneurysm was selected for occlusion to simplify the treatment of the aneurysm and to maximize the probability to achieve recovery., (Copyright: © Zhang et al.)

Ferroptosis, a new type of cell death has been found to aggravate intestinal ischemia/reperfusion (I/R) injury. However, little is known about the changes of gut microbiota and metabolites in intestinal I/R and the role of gut microbiota metabolites on ferroptosis-induced intestinal I/R injury. This study aimed to establish a mouse intestinal I/R model and ileum organoid hypoxia/reoxygenation (H/R) model to explore the changes of the gut microbiota and metabolites during intestinal I/R and protective ability of capsiate (CAT) against ferroptosis-dependent intestinal I/R injury. Intestinal I/R induced disturbance of gut microbiota and significant changes in metabolites. We found that CAT is a metabolite of the gut microbiota and that CAT levels in the preoperative stool of patients undergoing cardiopulmonary bypass were negatively correlated with intestinal I/R injury. Furthermore, CAT reduced ferroptosis-dependent intestinal I/R injury in vivo and in vitro. However, the protective effects of CAT against ferroptosis-dependent intestinal I/R injury were abolished by RSL3, an inhibitor of glutathione peroxidase 4 (Gpx4), which is a negative regulator of ferroptosis. We also found that the ability of CAT to promote Gpx4 expression and inhibit ferroptosis-dependent intestinal I/R injury was abrogated by JNJ-17203212, an antagonist of transient receptor potential cation channel subfamily V member 1 (TRPV1). This study suggests that the gut microbiota metabolite CAT enhances Gpx4 expression and inhibits ferroptosis by activating TRPV1 in intestinal I/R injury, providing a potential avenue for the management of intestinal I/R injury.

We lack empirical evidence for the relative importance of microbial functional attributes vs taxonomic attributes in regulating specified soil processes related to carbon (C) and nitrogen (N) cycling, which has hindered our ability to predict the responses of ecosystem multifunctionality to environmental changes. Here, we collected soil samples from a long-term experimental field with eight inorganic and organic fertilization treatments and evaluated the linkage between microbial functional attributes (abundance of functional genes), taxonomic attributes (microbial taxonomic composition), and soil processes including soil respiration, denitrification and nitrification. Long-term fertilization had no significant effect on the bacterial or fungal alpha-diversity. The treatments of chicken manure and sewage sludge addition significantly altered the rates of soil respiration, denitrification and nitrification, which were significantly correlated with the abundances of relevant functional genes. Random forest model indicated that the abundance of functional genes was the main diver for the rate of soil processes. The predominant effect of microbial functional attributes in driving soil processes was maintained when simultaneously accounting for multiple abiotic (total C, total N and soil pH) and biotic drivers (bacterial and fungal community structure), indicating that microbial functional attributes were the predominant driver predicting the rate of soil respiration, denitrification and nitrification. Our results suggested the importance of developing a functional gene-centric framework to incorporate microbial communities into biogeochemical models, which may provide new insights into the biodiversity-functions relationship and have implications for future management of the consequences of biodiversity loss for ecosystem multifunctionality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We demonstrate microwave dressing on ultracold, fermionic ^{23}Na^{40}K ground-state molecules and observe resonant dipolar collisions with cross sections exceeding 3 times the s-wave unitarity limit. The origin of these interactions is the resonant alignment of the approaching molecules' dipoles along the intermolecular axis, which leads to strong attraction. We explain our observations with a conceptually simple two-state picture based on the Condon approximation. Furthermore, we perform coupled-channel calculations that agree well with the experimentally observed collision rates. The resonant microwave-induced collisions found here enable controlled, strong interactions between molecules, of immediate use for experiments in optical lattices.

Microbiota in urban green spaces underpin ecosystem services that are essential to environmental health and human wellbeing. However, the factors shaping the microbial communities in urban green spaces, especially those associated with turf grass phyllosphere, remain poorly understood. The lack of this knowledge greatly limits our ability to assess ecological, social and recreational benefits of urban green spaces in the context of global urbanization. In this study, we used amplicon sequencing to characterize soil and grass phyllosphere bacterial communities in 40 urban green spaces and three minimally disturbed national parks in Victoria, Australia. The results indicated that urbanization might have shown different impacts on soil and grass phyllosphere microbial communities. The bacterial diversity in soil but not in grass phyllosphere was significantly higher in urban green spaces than in national parks. Principal coordinate analysis revealed significant differences in the overall patterns of bacterial community composition between urban green spaces and national parks for both soil and grass phyllosphere. Industrial development, as represented by the number of industries in the region, was identified as a key driver shaping the bacterial community profiles in urban green spaces. Variation partitioning analysis suggested that industrial factors together with their interaction with other factors explained 20% and 28% of the variances in soil and grass phyllosphere bacterial communities, respectively. The findings highlight the importance of industrial development in driving the spatial patterns of urban microbiomes, and have important implication for the management of microbiomes in urban green spaces., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The emergence of quasiparticles in interacting matter represents one of the cornerstones of modern physics. However, in the vicinity of a quantum critical point, the existence of quasiparticles comes under question. Here, we created Bose polarons near quantum criticality by immersing atomic impurities in a Bose-Einstein condensate (BEC) with near-resonant interactions. Using radiofrequency spectroscopy, we probed the energy, spectral width, and short-range correlations of the impurities as a function of temperature. Far below the superfluid critical temperature, the impurities formed well-defined quasiparticles. Their inverse lifetime, given by their spectral width, increased linearly with temperature at the so-called Planckian scale, consistent with quantum critical behavior. Close to the BEC critical temperature, the spectral width exceeded the impurity's binding energy, signaling a breakdown of the quasiparticle picture., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Plant microbiome, as the second genome of plant, and the interface between human and environmental microbiome, represents a potential pathway of human exposure to environmental pathogens and resistomes. However, the impact of host identity on the profile of resistomes in plant phyllosphere is unclear and this knowledge is vital for establishing a framework to evaluate the dissemination of antibiotic resistance via the plant microbiome. Here, we explored the phyllosphere microbiome and resistomes in 12 selected plant species. By using High-throughput quantitative PCR, we identified a total of 172 unique resistance genes in plant phyllosphere microbiome, which was significantly divergent from the profile of resistomes in associated soils (Adonis, P < 0.01). Host identity had a significant effect on the plant resistome, which was mainly attributed to the dissimilarity of phyllosphere bacterial phylogeny across different plants. We identified a core set of plant resistomes shared in more than 80% of samples, which accounted for more than 64% of total resistance genes. These plant core resistomes conferred resistance to antibiotics that are commonly administered to humans and animals. Our findings extend our knowledge regarding the resistomes in plant phyllosphere microbiome and highlight the role of host identity in shaping the plant associated antibiotic resistance genes., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Sepsis is a major cause of death for ICU patients. Sepsis development depends heavily on the presence of mature IL-1β cytokine. This study evaluates the potential therapeutic properties of a bioactive compound known as 6-gingerol on sepsis. This compound has previously been demonstrated to possess anti-inflammatory properties both in vivo and in vitro., Methods: C57BL/6 mice was used to establish models of sepsis by means of cecal ligation and puncture (CLP). Upon treatment with 6-gingerol, we assessed the survival rate of mice and measured the levels of key pro-inflammatory cytokines in serum and colon tissues. Sepsis pathogenesis was further explored using the RAW264.7 cell line and bone marrow-derived macrophages (BMDMs) treated with ATP and lipopolysaccharide (LPS). The impact of 6-gingerol on pyroptosis was also examined. In addition, we assessed the role of MAPK signaling in 6-gingerol-induced effects in BMDMs and RAW264.7 cells., Results: In CLP mice, 6-gingerol significantly ameliorated sepsis development, which was associated with the reduction of serum IL-1β. In BMDMs and RAW264.7 cells, 6-gingerol strongly attenuated pyroptosis as well as the release of caspase-1p20, HMGB1, mature IL-1β, IL-18 in response to ATP and LPS treatment. 6-Gingerol conferred these effects by blocking MAPK activation. Exposure to an ERK agonist (EGF) reversed effects of 6-gingerol, causing pyroptosis, LDH and caspase-1p20 release., Conclusions: By targeting MAPK signaling, 6-gingerol significantly suppressed secretion of pro-inflammatory cytokines and inhibited macrophage cells pyroptosis resulting in overall inhibition of sepsis development., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Hepatic ischemia-reperfusion (IR) injury is the leading cause of liver dysfunction and failure after liver resection or transplantation and lacks effective therapeutic strategies. Here, we applied a systematic proteomic analysis to identify the prominent contributors to IR-induced liver damage and promising therapeutic targets for this condition. Based on an unbiased proteomic analysis, we found that toll-interacting protein (Tollip) expression was closely correlated with the hepatic IR process. RNA sequencing analysis and phenotypic examination showed a dramatically alleviated hepatic IR injury by Tollip deficiency both in vivo and in hepatocytes. Mechanistically, Tollip interacts with apoptosis signal-regulating kinase 1 (ASK1) and facilitates the recruitment of tumor necrosis factor receptor-associated factor 6 (TRAF6) to ASK1, leading to enhanced ASK1 N-terminal dimerization and the subsequent activation of downstream mitogen-activated protein kinase (MAPK) signaling. Furthermore, the Tollip methionine and phenylalanine motif and TRAF6 ubiquitinating activity are required for Tollip-regulated ASK1-MAPK axis activation. Conclusion: Tollip is a regulator of hepatic IR injury by facilitating ASK1 N-terminal dimerization and the resultant c-Jun N-terminal kinase/p38 signaling activation. Inhibiting Tollip or its interaction with ASK1 might be promising therapeutic strategies for hepatic IR injury., (© 2019 by the American Association for the Study of Liver Diseases.)

Urban green spaces are closely related to the activities and health of urban residents. Turf grass and soil are two major interfaces between the environmental and human microbiome, which represent potential pathways for the spread of antibiotic resistance genes (ARGs) from environmental to human microbiome through skin-surface contact. However, the information regarding the prevalence of ARGs in urban green spaces and drivers in shaping their distribution patterns remain unclear. Here, we profiled a wide spectrum of ARGs in grass phyllosphere and soils from 40 urban parks across Greater Melbourne, Australia, using high throughput quantitative PCR. A total of 217 and 218 unique ARGs and MGEs were detected in grass phyllosphere and soils, respectively, conferring resistance to almost all major classes of antibiotics commonly used in human and animals. The plant microbiome contained a core resistome, which occupied >84% of the total abundance of ARGs. In contrast, no core resistome was identified in the soil microbiome. The difference between plant and soil resistome composition was attributed to the difference in bacterial community structure and intensity of environmental and anthropogenic influence. Most importantly, the abundance of ARGs in urban green spaces was significantly positively related to industrial factors including total number of business, number of manufacturing, and number of electricity, gas, water and waste services in the region. Structural equation models further revealed that industrial distribution was a major factor shaping the ARG profiles in urban green spaces after accounting for multiple drivers. These findings have important implications for mitigation of the potential risks posed by ARGs to urban residents., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Medical ultrasound images are corrupted by speckle noise, and despeckling methods are required to effectively and efficiently reduce speckle noise while simultaneously preserving details of tissues. This paper proposes a despeckling approach named the Gabor-based anisotropic diffusion coupled with the lattice Boltzmann method (GAD-LBM), which uses the lattice Boltzmann method (LBM) to fast solve the partial differential equation of an anisotropic diffusion model embedded with the Gabor edge detector. We evaluated the GAD-LBM on both synthetic and clinical ultrasound images, and the experimental results suggested that the GAD-LBM was superior to other nine methods in speckle suppression and detail preservation. For synthetic and clinical images, the computation time of the GAD-LBM was about 1/90 to 1/20 of the GAD solved with the finite difference, indicating the advantage of the GAD-LBM in efficiency. The GAD-LBM not only has excellent ability of noise reduction and detail preservation for ultrasound images, but also has advantages in computational efficiency.

Plant growth and development depends on its ability to maintain optimal cellular homeostasis during abiotic and biotic stresses. Cleistogenes songorica , a xerophyte desert plant, is known to have novel drought stress adaptation strategies and contains rich pools of stress tolerance genes. Proteins encoded by Late Embryogenesis Abundant (LEA) family genes promote cellular activities by functioning as disordered molecules, or by limiting collisions between enzymes during stresses. To date, functions of the LEA family genes have been heavily investigated in many plant species except perennial monocotyledonous species. In this study, 44 putative LEA genes were identified in the C. songorica genome and were grouped into eight subfamilies, based on their conserved protein domains and domain organizations. Phylogenetic analyses indicated that C. songorica Dehydrin and LEA&#95;2 subfamily proteins shared high sequence homology with stress responsive Dehydrin proteins from Arabidopsis. Additionally, promoter regions of CsLEA&#95;2 or CsDehydrin subfamily genes were rich in G-box, drought responsive (MBS), and/or Abscisic acid responsive (ABRE) cis -regulatory elements. In addition, gene expression analyses indicated that genes from these two subfamilies were highly responsive to heat stress and ABA treatment, in both leaves and roots. In summary, the results from this study provided a comprehensive view of C. songorica LEA genes and the potential applications of these genes for the improvement of crop tolerance to abiotic stresses.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent and complex disease that confers a high risk of severe liver disorders. Despite such public and clinical health importance, very few effective therapies are currently available for NAFLD. We report a protective function and the underlying mechanism of dual-specificity phosphatase 14 (DUSP14) in NAFLD and related metabolic disorders. Insulin resistance, hepatic lipid accumulation, and concomitant inflammatory responses, key pathological processes involved in NAFLD development, were significantly ameliorated by hepatocyte-specific DUSP14 overexpression (DUSP14-HTG) in high-fat diet (HFD)-induced or genetically obese mouse models. By contrast, specific DUSP14 deficiency in hepatocytes (DUSP14-HKO) aggravated these pathological alterations. We provided mechanistic evidence that DUSP14 directly binds to and dephosphorylates transforming growth factor β-activated kinase 1 (TAK1), resulting in the reduced activation of TAK1 and its downstream signaling molecules c-Jun N-terminal kinase 1 (JNK), p38, and nuclear factor kappa B NF-κB. This effect was further evidenced by the finding that inhibiting TAK1 activity effectively attenuated the deterioration of glucolipid metabolic phenotype in DUSP14-HKO mice challenged by HFD administration. Furthermore, we identified that both the binding domain and the phosphatase activity of DUSP14 are required for its protective role against hepatic steatosis, because interruption of the DUSP14-TAK1 interaction abolished the mitigative effects of DUSP14., Conclusion: Hepatocyte DUSP14 is required for maintaining hepatic metabolic homeostasis and for suppressing inflammation, a novel function that relies on constraining TAK1 hyperactivation. (Hepatology 2018;67:1320-1338)., (© 2017 by the American Association for the Study of Liver Diseases.)

Hepatic ischemia-reperfusion (IR) injury is a common clinical issue lacking effective therapy and validated pharmacological targets. Here, using integrative 'omics' analysis, we identified an arachidonate 12-lipoxygenase (ALOX12)-12-hydroxyeicosatetraenoic acid (12-HETE)-G-protein-coupled receptor 31 (GPR31) signaling axis as a key determinant of the hepatic IR process. We found that ALOX12 was markedly upregulated in hepatocytes during ischemia to promote 12-HETE accumulation and that 12-HETE then directly binds to GPR31, triggering an inflammatory response that exacerbates liver damage. Notably, blocking 12-HETE production inhibits IR-induced liver dysfunction, inflammation and cell death in mice and pigs. Furthermore, we established a nonhuman primate hepatic IR model that closely recapitulates clinical liver dysfunction following liver resection. Most strikingly, blocking 12-HETE accumulation effectively attenuated all pathologies of hepatic IR in this model. Collectively, this study has revealed previously uncharacterized metabolic reprogramming involving an ALOX12-12-HETE-GPR31 axis that functionally determines hepatic IR procession. We have also provided proof of concept that blocking 12-HETE production is a promising strategy for preventing and treating IR-induced liver damage.

Objective: To investigate the expression levels of LINCRNA00346 in tissues and cells in patients with non-small cell lung cancer (NSCLC) and its biological function., Patients and Methods: The relative expression levels of LINC 00346 in 70 cases of tissues and cells in NSCLC patients were detected via quantitative reverse transcription polymerase chain reaction (qRT-PCR). The specific interference sequences of LINC 00346 were designed and the transfection efficiency after 48 h was detected. The effect of LINC 00346 on the proliferation capacity of NSCLC cells was studied via cell counting kit-8 (CCK-8) assay. After the interference in LINC 00346 expression in NSCLC cells, the changes in cell cycle and apoptosis were detected via flow cytometry. The nude-mouse transplanted tumor model was established to study the effect of LINC 00346 on in vivo tumorigenic ability of tumor cells. After the interference in LINC 00346 expression, the changes in expressions of molecular markers in the downstream signaling pathway were detected via Western blotting., Results: The LINC 00346 expressions were relatively high in 50 cases of tissues and 5 kinds of tumor cells in NSCLC patients. After the interference in LINC 00346 expression, the apoptosis of tumor cells was promoted, the cell proliferation was inhibited, and the cell cycle was arrested in G1-G0 phase. The animal experiment revealed that the interference in LINC 00346 expression could inhibit the in vivo tumorigenic ability of tumor cells. Western blotting showed that LINC 00346 could exert its function through partially regulating the Janus kinase/signal transducer and activator of transcription 3 (JAK-STAT3) signaling pathway., Conclusions: The expressions of LINC 00346 were relatively high in NSCLC tissues and cells. LINC 00346 promotes the proliferation and inhibits the apoptosis of NSCLC cells through regulating the JAK-STAT3 signaling pathway.

This corrects the article DOI: 10.1038/nm.4290.

Aim: To predict the visual outcome in patients undergoing macular hole surgery by two novel three-dimensional morphological parameters on optical coherence tomography (OCT): area ratio factor (ARF) and volume ratio factor (VRF)., Methods: A clinical case series was conducted, including 54 eyes of 54 patients with an idiopathic macular hole (IMH). Each patient had an OCT examination before and after surgery. Morphological parameters of the macular hole, such as minimum diameter, base diameter, and height were measured. Then, the macular hole index (MHI), tractional hole index (THI), and hole form factor (HFF) were calculated. Meanwhile, novel postoperative macular hole (MH) factors, ARF and VRF were calculated by three-dimensional morphology. Bivariate correlations were performed to acquire asymptotic significance values between the steady best corrected visual acuity (BCVA) after surgery and 2D/3D arguments of MH by the Pearson method with two-tailed test. All significant factors were analyzed by the receiver operating characteristic (ROC) curve analysis of SPSS software which were responsible for vision recovery. ROC curves analyses were performed to further discuss the different parameters on the prediction of visual outcome., Results: The mean and standard deviation values of patients' age, symptoms duration, and follow-up time were 64.8±8.9y (range: 28-81), 18.6±11.5d (range: 2-60), and 11.4±0.4mo (range: 6-24), respectively. Steady-post-BCVA analyzed with bivariate correlations was found to be significantly correlated with base diameter ( r =0.521, P <0.001), minimum diameter ( r =0.514, P <0.001), MHI ( r =-0.531, P <0.001), THI ( r =-0.386, P =0.004), HFF ( r =-0.508, P <0.001), and ARF ( r =-0.532, P <0.001). Other characteristic parameters such as age, duration of surgery, height, diameter hole index, and VRF were not statistically significant with steady-post-BCVA. According to area under the curve (AUC) values, values of ARF, MHI, HFF, minimum diameter, THI, and base diameter are 0.806, 0.772, 0.750, 0.705, 0.690, and 0.686, respectively. However, Steady-post-BCVA analysis with bivariate correlations for VRF was no statistical significance. Results of ROC curve analysis indicated that the MHI value, HFF, and ARF was greater than 0.427, 1.027 and 1.558 respectively which could correlate with better visual acuity., Conclusion: Compared with MHI and HFF, ARF could effectively express three-dimensional characteristics of macular hole and achieve better sensitivity and specificity. Thus, ARF could be the most effective parameter to predict the visual outcome in macular hole surgery.

Coherence, the stability of the relative phase between quantum states, is central to quantum mechanics and its applications. For ultracold dipolar molecules at sub-microkelvin temperatures, internal states with robust coherence are predicted to offer rich prospects for quantum many-body physics and quantum information processing. We report the observation of stable coherence between nuclear spin states of ultracold fermionic sodium-potassium (NaK) molecules in the singlet rovibrational ground state. Ramsey spectroscopy reveals coherence times on the scale of 1 second; this enables high-resolution spectroscopy of the molecular gas. Collisional shifts are shown to be absent down to the 100-millihertz level. This work opens the door to the use of molecules as a versatile quantum memory and for precision measurements on dipolar quantum matter., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)