Migration of natural organic matter and Pseudomonas fluorescens-associated polystyrene on natural substrates in aquatic environments.

This study investigated the migration behavior of microplastics (MPs) covered with natural organic matter (NOM) and biofilm on three substrates (silica, Pseudomonas fluorescent and Pseudomonas aeruginosa biofilms) in various ionic strengths, focusing on the alterations in surface properties based on surface energy theory that affected their deposition and release processes. Peptone and Pseudomonas fluorescens were employed to generate NOM-attached and biofilm-coated polystyrene (PS) (NOM-PS and Bio-PS). NOM-PS and Bio-PS both exhibited different surface properties, as increased roughness and particle sizes, more hydrophilic surfaces and altered zeta potentials which increased with ionic strength. Although the deposition of NOM-PS on biofilms were enhanced by higher ionic strengths and the addition of Ca2+, while Bio-PS deposited less on biofilms and more on the silica surface. Both types exhibited diffusion-driven adsorption on the silica surface, with Bio-PS also engaging in synergistic and competitive interactions on biofilm surfaces. Release tests revealed that NOM-PS and Bio-PS were prone to release from silica than from biofilms. The Extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory furtherly demonstrated that mid-range electrostatic (EL) repulsion had significantly impacts on NOM-PS deposition, and structural properties of extracellular polymeric substances (EPS) and substrate could affect Bio-PS migration.

Escherichia coli LTB26 mutant enhances immune responses to rotavirus antigen VP8 in a mouse model.

Adjuvant is a major supplementary component of vaccines to boost adaptive immune responses. To select an efficient adjuvant from the heat-labile toxin B subunit (LTB) of E. coli, four LTB mutants (numbered LTB26, LTB34, LTB57, and LTB85) were generated by multi-amino acid random replacement. Mice have been intranasally vaccinated with human rotavirus VP8 admixed. Among the four mutants, enzyme-linked immunosorbent assay (ELISA) revealed that LTB26 had enhanced mucosal immune adjuvanticity compared to LTB, showing significantly enhanced immune responses in both serum IgG and mucosal sIgA levels. The 3D modeling analysis suggested that the enhanced immune adjuvanticity of LTB26 might be due to the change of the first LTB α-helix to a ß-sheet. The molecular mechanism was studied using transcriptomic and flow cytometric (FCM) analysis. The transcriptomic data demonstrated that LTB26 enhanced immune response by enhancing B cell receptor (BCR) and major histocompatibility complex (MHC) II+-related pathways. Furthermore, LTB26 promoted Th1 and Th2-type immune responses which were confirmed by detecting IFN-γ and IL-4 expression levels. Immunohistochemical analysis demonstrated that LTB26 enhanced both Th1 and Th2 type immunity. Therefore, LTB26 was a potent mucosal immune adjuvant meeting the requirement for use in human clinics in the future.

Joint Exfoliation of MXene by Dimensional Mismatched SiC/ZIF-67 Toward Multifunctional Flame Retardant Thermoplastic Polyurethane.

The single-layer MXene fully demonstrates the advantages of 2D materials, especially catalytic, conductive, and mechanical properties. However, the high energy consumption and low efficiency faced by MXene in the divestiture process are still challenges that need to be solved urgently. In this article, dimension mismatch and collaborative stripping strategies are skillfully combined to easily realize the transformation from multi-layer MXene to single layer. In addition, the functionalized MXene@SiC@polyaniline (MXene@SiC@PANI) nano-hybrid materials are used as fillers to improve the thermal conductivity, flame retardant, and antibacterial properties of thermoplastic polyurethane (TPU). The surface temperature of TPU/MXene@SiC@PANI composites increased from 33.4 °C to 59.8 °C within 10 s. In addition, the antibacterial efficiency of TPU composites against Escherichia coli and Staphylococcus aureus is 69.6% and 88.9%, respectively. Compared with pure TPU, the peak heat release rate and total heat release are reduced by 71.4% and 34.6%, respectively. The flame-retardant mechanism of MXene hybrid materials is systematically discussed. It is worth noting that the introduction of PANI enhances the compatibility between the filler and the polymer, effectively maintaining the mechanical properties of the TPU itself. This work provides a convenient method for the multi-functional practical application of TPU.

Copper-Catalyzed Remote Asymmetric Yne-Allylic Substitution of Yne-Allylic Esters with Anthrones.

Anthrones are key structural motifs in many natural products and pharmaceutical chemicals. However, due to its unique tricyclic aromatic structure, the synthetic space for the development of chiral anthrone derivatives is largely limited. By utilizing the potential of the copper-catalyzed remote asymmetric yne-allylic substitution reaction, we describe the first example of copper-catalyzed highly regio- and enantioselective remote yne-allylic substitution on various yne-allylic esters with anthrones under a mild reaction condition, which afforded a range of enantioenriched 1,3-enynes with exhibiting broad functional group tolerance across 51 examples.

The cerebellum modulates thirst.

The cerebellum, a phylogenetically ancient brain region, has long been considered strictly a motor control structure. Recent studies have implicated the cerebellum in cognition, sensation, emotion and autonomic function, making it an important target for further investigation. Here, we show that cerebellar Purkinje neurons in mice are activated by the hormone asprosin, leading to enhanced thirst, and that optogenetic or chemogenetic activation of Purkinje neurons induces rapid manifestation of water drinking. Purkinje neuron-specific asprosin receptor (Ptprd) deletion results in reduced water intake without affecting food intake and abolishes asprosin's dipsogenic effect. Purkinje neuron-mediated motor learning and coordination were unaffected by these manipulations, indicating independent control of two divergent functions by Purkinje neurons. Our results show that the cerebellum is a thirst-modulating brain area and that asprosin-Ptprd signaling may be a potential therapeutic target for the management of thirst disorders.

Clinical efficacy of thalidomide for various genotypes of beta thalassemia.

OBJECTIVE: The objective of this study was to investigate the therapeutic efficacy of thalidomide across various genotype presentations of ß-thalassemia so as to facilitate the early screening of thalidomide-sensitive thalassemia cases and to understand the impact of iron overload on thalidomide. METHODS: From our initial sample of 52 patients, we observed 48 patients with ß-thalassemia for two years after administration of thalidomide. This cohort included 34 patients with transfusion-dependent thalassemia (TDT) and 14 patients with non-transfusion-dependent thalassemia (NTDT). We recorded the values of hemoglobin (Hb), fetal hemoglobin (HbF), and serum ferritin (SF) in the baseline period and at 1, 3, 6, 12, 18, and 24 months after enrollment, as well as the pre- and post-treatment blood transfusion volume in all 48 cases. According to the increase in Hb levels from baseline during the 6-month observation period, the response to thalidomide was divided into four levels: main response (MaR), minor response (MiR), slow response (SLR), and no response (NR). A decrease in serum ferritin levels compared to baseline was considered alleviation of iron overload. We calculated the overall response rate (ORR) as follows: ORR = MaR + MiR + SLR/number of observed cases. RESULTS: The ORR was 91.7% (44/48 cases), and 72.9% showed MaR (35/48 cases). Among the 34 patients with TDT, 21 patients (61.8%) were free of blood transfusion, and the remaining 13 patients still required blood transfusion, but their total blood transfusion volume reduced by 31.3% when compared to the baseline. We found a total of 33 cases with 10 combinations of advantageous genes, which included 5 cases with ßCD41-42/ßCD17 and 6 cases with ßCD41-42/ß-28. Based on the treatment outcomes among the 48 cases in the observation group, there were 33 cases in the MaR group and 15 cases in the SLR/NR group. There was a difference in HbF between the two groups at baseline (P = 0.041). There were significant differences between the two groups in Hb and HbF at the time points of 6 and 12 months, respectively (P < 0.001). Compared to the baseline measurement, there was a significant decrease in the level of SF at months 12 and 24 (P < 0.001). CONCLUSION: In this study, we identified 10 ß-thalassemia gene combinations that were sensitive to thalidomide. These gene combinations can be used for initial screening and to predict the therapeutic effect of thalidomide in clinical practice. We examined the therapeutic response to thalidomide and found that the administration of thalidomide in combination with standardized iron removal was more beneficial in reducing iron overload.

DiffRecon: Diffusion-based CT reconstruction with cross-modal deformable fusion for DR-guided non-coplanar radiotherapy.

In non-coplanar radiotherapy, DR is commonly used for image guiding which needs to fuse intraoperative DR with preoperative CT. But this fusion task performs poorly, suffering from unaligned and dimensional differences between DR and CT. CT reconstruction estimated from DR could facilitate this challenge. Thus, We propose a unified generation and registration framework, named DiffRecon, for intraoperative CT reconstruction based on DR using the diffusion model. Specifically, we use the generation model for synthesizing intraoperative CTs to eliminate dimensional differences and the registration model for aligning synthetic CTs to improve reconstruction. To ensure clinical usability, CT is not only estimated from DR but the preoperative CT is also introduced as prior. We design a dual-encoder to learn prior knowledge and spatial deformation among pre- and intra-operative CT pairs and DR parallelly for 2D/3D feature deformable conversion. To calibrate the cross-modal fusion, we insert cross-attention modules to enhance the 2D/3D feature interaction between dual encoders. DiffRecon has been evaluated by both image quality metrics and dosimetric indicators. The high image synthesis metrics are with RMSE of 0.02±0.01, PSNR of 44.92±3.26, and SSIM of 0.994±0.003. The mean gamma passing rates between rCT and sCT for 1%/1 mm, 2%/2 mm and 3%/3 mm acceptance criteria are 95.2%, 99.4% and 99.9% respectively. The proposed DiffRecon can reconstruct CT accurately from a single DR projection with excellent image generation quality and dosimetric accuracy. These demonstrate that the method can be applied in non-coplanar adaptive radiotherapy workflows.

Exosomes originating from neural stem cells undergoing necroptosis participate in cellular communication by inducing TSC2 upregulation of recipient cells following spinal cord injury.

ABSTRACT: We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord injury. While exosomes are recognized as playing a pivotal role in neural stem cells exocrine function, their precise function in spinal cord injury remains unclear. To investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury, we conducted single-cell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord injury. Subsequently, we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted exosomes. The results showed that necroptosis did not significantly impact the fundamental characteristics or number of exosomes. Transcriptome sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs, 104 long non-coding RNAs, 720 circular RNAs, and 14 microRNAs compared with the control group. Construction of a competing endogenous RNA network identified the following hub genes: tuberous sclerosis 2 (Tsc2), solute carrier family 16 member 3 (Slc16a3), and forkhead box protein P1 (Foxpl). Notably, a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord injury. TSC2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury zone. Furthermore, in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other cells. Further assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling pathways. In addition, Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling pathways. Collectively, these findings confirm that exosomes derived from neural stem cells undergoing necroptosis play an important role in cellular communication after spinal cord injury and induce TSC2 upregulation in recipient cells.

Enhanced Optical Limiting of Gold Nanoparticles/Porous Carbon Nanocomposites.

With the wide application of laser weapons, the requirements of laser protection technology are becoming more and more strict. Therefore, it is important to find ideal optical limiting (OL) materials to protect human eyes and detectors. In this work, the nonlinear optical responses of gold nanoparticles/porous carbon (Au NPs/PC) nanocomposites prepared by the reduction method were studied using the nanosecond Z-scan technique. Compared with porous carbon, the Au NPs/PC nanocomposites show a lower damage threshold, a bigger optical limiting index and a wider absorption spectrum. The interaction between gold nanoparticles and porous carbon enhances the nonlinear scattering effect of suspended bubbles. These results indicate that Au NPs composites have potential applications in the protection of human eyes and detectors.

Preparation of Sn-Doped Ga2O3 Thin Films and MSM Ultraviolet Detectors Using Magnetron Co-Sputtering.

Sn-doped Ga2O3 thin films and metal-semiconductor-metal (MSM) ultraviolet detectors were prepared using the co-sputtering method to enhance their photoelectric performance. The results revealed that Sn doping can effectively change the optical and electrical properties of thin films, greatly improving the photoelectric responsiveness of the devices. Through microstructure testing results, all of the thin film structures were determined to be monoclinic beta phase gallium oxide. At a DC power of 30 W, the thickness of the Sn-doped thin film was 430 nm, the surface roughness of the thin film was 4.94 nm, and the carrier concentration, resistivity, and mobility reached 9.72 × 1018 cm-3, 1.60 × 10-4 Ω·cm, and 45.05 cm3/Vs, respectively. The optical results show that Sn doping clearly decreases the transmission of thin films and that the bandgap can decrease to 3.91 eV. Under 30 W DC power, the photo dark current ratio of the detector can reach 101, time responses of tr = 31 s and tf = 22.83 s were obtained, and the spectral responsivity reached 19.25 A/W.

UBXN3B is crucial for B lymphopoiesis.

BACKGROUND: The ubiquitin regulatory X (UBX) domain-containing proteins (UBXNs) are putative adaptors for ubiquitin ligases and valosin-containing protein; however, their in vivo physiological functions remain poorly characterised. We recently showed that UBXN3B is essential for activating innate immunity to DNA viruses and controlling DNA/RNA virus infection. Herein, we investigate its role in adaptive immunity. METHODS: We evaluated the antibody responses to multiple viruses and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza in tamoxifen-inducible global and constitutive B cell-specific Ubxn3b knockout mice; quantified various immune populations, B lineage progenitors/precursors, B cell receptor (BCR) signalling and apoptosis by flow cytometry, immunoblotting and immunofluorescence microscopy. We also performed bone marrow transfer, single-cell and bulk RNA sequencing. FINDINGS: Both global and B cell-specific Ubxn3b knockout mice present a marked reduction in small precursor B-II (>60%), immature (>70%) and mature B (>95%) cell numbers. Transfer of wildtype bone marrow to irradiated global Ubxn3b knockouts restores normal B lymphopoiesis, while reverse transplantation does not. The mature B population shrinks rapidly with apoptosis and higher pro and activated caspase-3 protein levels were observed following induction of Ubxn3b knockout. Mechanistically, Ubxn3b deficiency leads to impaired pre-BCR signalling and cell cycle arrest. Ubxn3b knockout mice are highly vulnerable to respiratory viruses, with increased viral loads and prolonged immunopathology in the lung, and reduced production of virus-specific IgM/IgG. INTERPRETATION: UBXN3B is essential for B lymphopoiesis by maintaining constitutive pre-BCR signalling and cell survival in a cell-intrinsic manner. FUNDING: United States National Institutes of Health grants, R01AI132526 and R21AI155820.

Copper-Catalyzed Dual Remote Asymmetric Vinylogous Alkynylallylic Substitution of Yne-Allylic Esters with Coumarins.

Chiral coumarins and their derivatives are ubiquitous structural motifs found in an array of biologically and therapeutically active natural products and drugs. Herein, a highly enantioselective dual remote copper-catalyzed vinylogous alkynylallylic substitution of yne-allylic esters with coumarins has been developed. The practicality of this method is exemplified by the use of readily available starting materials; mild reaction conditions; excellent regio-, enantio-, and stereoselectivities; and the very broad substrate scope (67 examples), while the scalability and further applications of this method are illustrated by the gram-scale reaction and the series of derivations of the products.

DNA Origami Enhanced Cytokine Immunotherapy for Alleviating Renal Ischemia-Reperfusion Injury.

Renal ischemia-reperfusion injury (IRI) is a major contributing factor to the development of acute kidney injury (AKI) and has resulted in considerable morbidity and mortality. Persistent inflammatory responses and excessive reactive oxygen species (ROS) in the kidney following IRI can severely delay tissue repair, making it challenging to effectively promote IRI regeneration. Herein, we report an approach to enhance immunotherapy using interleukin-10 (IL-10) to promote IRI regeneration by loading IL-10 onto rectangular DNA origami nanostructures (rDON). rDON can significantly enhance the renal accumulation and retention time of IL-10, enabling it to effectively polarize type 1 macrophages into type 2 macrophages, thereby significantly reducing proinflammatory factors and increasing anti-inflammatory factors. In addition, DNA origami helps mitigate the harmful effects of ROS during renal IRI. The administration of IL-10-loaded DNA origami effectively improves kidney function, resulting in a notable reduction in blood urea nitrogen, serum uric acid, and serum creatinine levels. Our study demonstrates that the integration of anti-inflammatory cytokines within DNA origami holds promise as a strategic approach for cytokine immunotherapy in patients with AKI and other renal disorders.

On-Surface Synthesis of Five-Membered Copper Metallacycles Using Terminal Alkynes.

We present our studies on the adsorption, deprotonation, and reactions of 4,4″-diethynyl-1,1':4',1″-terphenyl on Cu(111) under ultrahigh-vacuum conditions using scanning tunneling microscopy combined with density functional theory calculations. Sequential annealing treatments induce deprotonation of pristine molecules followed by chemical reactions, resulting in branched nanostructures. Within the nanostructures, a previously unreported, double-spot linkage is observed. Our density functional theory calculations unravel that this linkage corresponds to a five-membered copper metallacycle.

Ex Vivo Surgical Removal Versus Conservative Management of Small Asymptomatic Kidney Stones in Living Donors and Long-term Kidney Transplant Outcomes.

BACKGROUND: Donors with small asymptomatic kidney stones have been increasingly accepted because of organ shortages and advances in endoscopic urology. This study aims to evaluate and compare long-term living-donor kidney transplant outcomes following ex vivo surgical removal versus conservative management of donors' gifted asymptomatic stones. METHODS: Between January 2007 and December 2021, 119 kidney transplant recipients received stone-bearing kidneys, divided into the removal group (N = 63) and observation group (N = 56). We evaluated posttransplant stone events, urinary infections, kidney function, delayed graft function, length of hospital stay, and survival outcomes. RESULTS: After a median follow-up of 75.5 mo, the removal group had a 10.9% lower absolute incidence of stone events (7/56 [12.5%] versus 1/63 [1.6%]; hazard ratio, 0.08; 95% confidence interval, 0.01-0.77) and a 14.3% lower absolute incidence of urinary infections (16/56 [28.6%] versus 9/63 [14.3%]; hazard ratio, 0.42; 95% confidence interval, 0.19-0.95) than the observation group. The removal group also showed superior kidney graft function. The 2 groups had comparable length of hospital stay (11.0 versus 12.0 d; P = 0.297) and exhibited similar delayed graft function incidence (1/56 [1.8%] versus 2/63 [3.2%]; P = 1.000) and urinary stricture incidence (1/56 [1.8%] versus 3/63 [4.8%]; P = 0.621). Graft survival (P = 0.350) and patient survival (P = 0.260) were comparable between 2 groups. Subgroup analyses in recipients who received kidneys with stones <4 mm also reported similar results. CONCLUSIONS: Ex vivo surgical removal might outperform conservative management for donors' gifted asymptomatic kidney stones, improving long-term transplant outcomes and reducing stone events without increasing perioperative complications, even for stones <4 mm.

Porcine skeletal muscle typing in histochemical and in-situ RT-PCR analysis.

Currently, there are plenty of histochemical methods to classify pig muscle fibers, which confused the naming and classification of muscle fibers. This study aims to analyze the difference and correlation of 6 different histochemical methods and select the most suitable method for muscle fiber classification at the molecular and histomological levels by in-situ RT-PCR and enzyme histochemical methods. Muscle fiber samples, including psoas (PM), semitendinosus (SM) and trapezius muscle (TM), were collected from Large Spotted (LS), Lantang (LT) and Landrace (LR) pigs at their market-ages (LS at 150 d, LT at 210 d, and LR at 150 d). 6 kinds of histochemical methods combining actomyosin adenosine triphosphatase (AM-ATPase) with succinate dehydrogenase (SDH) enzyme were conducted to differentiate fiber types. 2 types of fibers (I and II) were differentiated by acid 2-fibre (2-AC) or alkaline 2-fibre classification(2-AL), 3 types of fibers (ßR, αR and αW) by 3-AC or 3-AL, and 4 types of fibers (I, IIa, IIx and IIb) by 4-AC, or 4-AL. Results showed that AC and AL muscle-fiber classification were consistent in reflecting the characteristics of muscle fibers(P > 0.05), but the color of each muscle fiber type was just opposite. AC methods may be superior to AL methods because of their clear staining background, the sensitivity to staining condition. But there were breed differences and tissue specificity in the optimal preincubation condition. The optimal acid preincubation condition for classifying muscle fibers was pH4.30 for LT, while pH 4.35 for the LS and LR pigs. Meanwhile the optimal acid preincubation condition was pH4.35 for PM, while pH4.40 for TM or SM. For further selection from 2, 3, 4-AC, in-situ RT-PCR was applied to detect the mRNA distribution of myosin heavy chain I (MyHC-I). By combining in-situ PCR with enzyme histochemistry methods, MyHC-I gene and its product - Type I fibrocytes were directly located in cells at both molecular level and morphological level. Compared with the cross-sectional area (CSA) of different muscle fibers (i.e. I, II, ßR, αR, αW, IIa, IIx and IIb) identified by enzyme histochemistry, it was found that the CSAs with stronger mRNA expression signal of MyHC-Ⅰ were closer to those of the Type I muscle fiber measured by 4-AC enzyme histochemistry (P > 0.05). Therefore, 4-AC may be considered as the most proper muscle typing method to study muscle fiber typing as well as meat quality. And the combination of in-situ RT-PCR and histochemistry may help better understand porcine muscle fiber characteristics and meat quality in pigs.

Subminimum Inhibitory Concentrations Tetracycline Antibiotics Induce Biofilm Formation in Minocycline-Resistant Klebsiella pneumonia by Affecting Bacterial Physical and Chemical Properties and Associated Genes Expression.

Biofilm formation of Klebsiella pneumoniae can protect bacteria from antibiotics and is difficult to eradicate. Thus, the influence of subinhibitory concentrations of antibiotics on bacteria is becoming increasingly important. Our study showed that subminimum inhibitory concentrations (sub-MICs) of tetracycline antibiotics can increase biofilm formation in minocycline-resistant Klebsiella pneumoniae clinical strains. However, in the bacterial adhesion and invasion experiments, the adhesion and invasion ability decreased and the survival rate of Galleria mellonella increased. Under sub-MICs of tetracycline antibiotics treatment, abnormal stretching of bacteria was observed by scanning electron microscopy. Treatment with sub-MICs of tetracyclines leads to increased surface hydrophobicity and eDNA content and decreased outer membrane permeability. The expression levels of the fimA, luxS, qseB, and qseC genes decreased, the expression level of mrkA increased, and the expression level of acrA was inconsistent under different tetracycline antibiotics treatments. Together, our results suggested that the increase in Klebsiella pneumoniae biofilm formation caused by sub-MICs of tetracycline antibiotics may occur by affecting bacterial physical and chemical properties and associated genes expression.

Targeting DBS to the centrolateral thalamic nucleus improves movement in a lesion-based model of acquired cerebellar dystonia in mice.

Dystonia is the third most common movement disorder and an incapacitating co-morbidity in a variety of neurologic conditions. Dystonia can be caused by genetic, degenerative, idiopathic, and acquired etiologies, which are hypothesized to converge on a "dystonia network" consisting of the basal ganglia, thalamus, cerebellum, and cerebral cortex. In acquired dystonia, focal lesions to subcortical areas in the network - the basal ganglia, thalamus, and cerebellum - lead to a dystonia that can be difficult to manage with canonical treatments, including deep brain stimulation (DBS). While studies in animal models have begun to parse the contribution of individual nodes in the dystonia network, how acquired injury to the cerebellar outflow tracts instigates dystonia; and how network modulation interacts with symptom latency remain as unexplored questions. Here, we present an electrolytic lesioning paradigm that bilaterally targets the cerebellar outflow tracts. We found that lesioning these tracts, at the junction of the superior cerebellar peduncles and the medial and intermediate cerebellar nuclei, resulted in acute, severe dystonia. We observed that dystonia is reduced with one hour of DBS of the centrolateral thalamic nucleus, a first order node in the network downstream of the cerebellar nuclei. In contrast, one hour of stimulation at a second order node in the short latency, disynaptic projection from the cerebellar nuclei, the striatum, did not modulate the dystonia in the short-term. Our study introduces a robust paradigm for inducing acute, severe dystonia, and demonstrates that targeted modulation based on network principles powerfully rescues motor behavior. These data inspire the identification of therapeutic targets for difficult to manage acquired dystonia.

Traceability Research on Geographic Erigeron breviscapus Based on High-Resolution Mass Spectrometry and Chemometric Analysis.

A method was developed to identify and trace the geographic sources of Erigeron breviscapus using high-resolution mass spectrometry and chemometrics. The representative samples were collected from the geographic area of Honghe Dengzhanhua and other areas in Yunnan province and Guizhou province. The data points could be determined well using the PCA and PLS-DA diagram. A total of 46 characteristic compounds were identified from Honghe Dengzhanhua and within Guizhou province, but 37 compounds were different from Honghe Dengzhanhua and other counties in Yunnan province. Two biomarkers were found from three regions. Their structures were inferred as 8-amino-7-oxononanoic acid and 8-hydroxyquinoline, and they had the same molecular composition. This may suggest that a possible synthesis pathway can be proven in the future.

Physalis Calyx seu Fructus inhibited pulmonary fibrosis through regulating Wnt/ß-catenin signaling pathway.

BACKGROUND: Pulmonary fibrosis is a chronic and advancing interstitial lung disease, and there is an urgent need for novel agents for its therapy. Physalis Calyx seu Fructus (PCF) has been utilized in traditional Chinese medicine to treat respiratory disorders with a long history, however, the therapeutic effect and mechanism of PCF against pulmonary fibrosis are still unclear. PURPOSE: To assess therapeutic efficacy and underlying mechanism of 75 % ethanol extract of PCF (PCF-EtOH) against pulmonary fibrosis, as well as to discover active constituents in PCF. METHODS: A bleomycin-stimulated mice model was established to assess potential therapy of PCF-EtOH against pulmonary fibrosis in vivo. A lipopolysaccharide-induced inflammatory model in RAW 264.7 cells and a transforming growth factor ß1-induced fibrosis model in MRC-5 cells were established to assess potential therapy and mechanisms of purified constituents in PCF-EtOH. UPLC-MS/MS analysis was adopted to ascertain the constituents of PCF-EtOH. Network pharmacology was employed to forecast targets of PCF against pulmonary fibrosis. RESULTS: PCF-EtOH ameliorated bleomycin-induced pulmonary fibrosis through repressing inflammatory response and extracellular matrix deposition. Meanwhile, PCF-EtOH inhibited Wnt/ß-catenin pathway through decreasing ß-catenin nuclear accumulation and promoting phosphorylation. Furthermore, withanolides and flavonoids were presumed to be main active compounds of PCF against pulmonary fibrosis based on the network pharmacology. Importantly, we found an extensive presence of withanolides in PCF-EtOH. Physapubescin, a typical withanolide in PCF-EtOH, inhibited the inflammatory response, extracellular matrix deposition, and Wnt/ß-catenin pathway. Notably, physapubescin demonstrated a more potent antifibrotic effect than pirfenidone, a clinically approved antifibrotic drug, in the tested model. CONCLUSION: Withanolides and flavonoids are responsible for the inhibitory effect of PCF-EtOH against pulmonary fibrosis. Withanolides may represent a class of promising therapeutic agents against pulmonary fibrosis, and an in-depth exploration is warranted to validate this proposition.