De novo assembly and characterization of the transcriptome of Morchella esculenta growth with selenium supplementation.

Although Morchella esculenta (L.) Pers. is an edible and nutritious mushroom with significant selenium (Se)-enriched potential, its biological response to selenium stimuli remains unclear. This study explored the effect of selenium on mushroom growth and the global gene expression profiles of M. esculenta. While 5 µg mL-1selenite treatment slightly promoted mycelia growth and mushroom yield, 10 µg mL-1significantly inhibited growth. Based on comparative transcriptome analysis, samples treated with 5 µg mL-1 and 10 µg mL-1 of Se contained 16,061 (452 upregulated and 15,609 downregulated) and 14,155 differentially expressed genes (DEGs; 800 upregulated and 13,355 downregulated), respectively. Moreover, DEGs were mainly enriched in the cell cycle, meiosis, aminoacyl-tRNA biosynthesis, spliceosome, protein processing in endoplasmic reticulum pathway, and mRNA surveillance pathway in both selenium-treated groups. Among these, MFS substrate transporter and aspartate aminotransferase genes potentially involved in Se metabolism and those linked to redox homeostasis were significantly upregulated, while genes involved in isoflavone biosynthesis and flavonoid metabolism were significantly downregulated. Gene expression levels increased alongside selenite treatment concentration, suggesting that high Se concentrations promoted M. esculenta detoxification. These results can be used to thoroughly explain the potential detoxification and Se enrichment processes in M. esculenta and edible fungi.

An insular cortical circuit required for itch sensation and aversion.

Itch encompasses both sensory and emotional dimensions, with the two dimensions reciprocally exacerbating each other. However, whether a shared neural circuit mechanism governs both dimensions remains elusive. Here, we report that the anterior insular cortex (AIC) is activated by both histamine-dependent and -independent itch stimuli. The activation of AIC elicits aversive emotion and exacerbates pruritogen-induced itch sensation and aversion. Mechanistically, AIC excitatory neurons project to the GABAergic neurons in the dorsal bed nucleus of the stria terminalis (dBNST). Manipulating the activity of the AIC → dBNST pathway affects both itch sensation and itch-induced aversion. Our study discovers the shared neural circuit (AIC â†’ dBNST pathway) underlying the itch sensation and aversion, highlights the critical role of the AIC as a central hub for the itch processing, and provides a framework to understand the neural mechanisms underlying the sensation and emotion interaction.

A trinity strategy enabled by iodine-loaded nitrogen-boron-doped carbon protective layer for dendrite-free zinc-ion batteries.

Although aqueous zinc ion batteries (AZIBs) have the merits of environmental friendliness, high safety and theoretical capacity, the slow kinetics associated with zinc deposition and unavoidable interfacial corrosion have seriously affected the commercialization of aqueous zinc ion batteries. In this work, an ingenious "trinity" design is proposed by applying a porous hydrophilic carbon-loaded iodine coating to the zinc metal surface (INBC@Zn), which simultaneously acts as an artificial protective layer, electrolyte additive and anode curvature regulator, so as to reduce the nucleation overpotential of Zn and promote the preferential deposition of (002) planes to some extent. With this synergistic effect, INBC@Zn exhibits high reversibility and strong side reaction inhibition. As a result, INBC@Zn shows high symmetric cycling stability up to 4500 h at 1 mA cm-2. An ultra-long cycle stability of 1500 cycles with high Coulombic efficiency (99.8 %) is achieved in the asymmetric cell. In addition, the INBC@Zn//NVO full cells exhibit impressive capacity retention (96 % after 1000 cycles at 3 A/g). Importantly, the designed pouch cell demonstrates stable performance and shows certain prospects for application. This work provides a facile and instructive approach toward the development of high-performance AZIBs.

Immunoproteasome Subunit Low Molecular Mass Peptide 2 (LMP2) Deficiency Ameliorates LPS/Aß1-42-Induced Neuroinflammation.

Low molecular mass peptide 2 (LMP2) is the ß1i subunit of immunoproteasome (iP) which plays a key role in neuroinflammatory responses, and inhibition of iP exhibits a high neuroprotective action against neurodegenerative diseases. Since neuroinflammation has been shown to be involved in the development and progression of Alzheimer's disease (AD), the aim of this study was to evaluate the anti-inflammatory role of LMP2 deficiency in AD in vivo and in vitro. Here, we found that LMP2 was upregulated in the brains of 5 × FAD and APP/PS1 mice and increased with age in C57/BL6 mice. We showed that the lack of LMP2 significantly decreased NLRP3 expression and downstream cytokine release in microglia, resulting in partially blocking Aß1-42- or LPS-induced inflammation in vivo and in vitro, which ameliorated cognitive deficits in aged rats and D-galactose + Aß1-42-treated rats. These results suggest that LMP2 contributes to the regulation of LPS-or Aß-driven innate immune responses by diminishing NLRP3 expression and clarify that inhibition of iP function may mediate the inflammatory-related cognitive phenotype.

The Lateral Parabrachial Nucleus Inputs to the Lateral Hypothalamus Trigger Nocifensive Behaviors.

The lateral parabrachial nucleus (LPBN) is known to play a key role in relaying noxious information from the spinal cord to the brain. Different LPBN efferent mediate different aspects of the nocifensive response. However, the function of the LPBN â†’ lateral hypothalamus (LH) circuit in response to noxious stimuli has remained unknown. Here, we show that LPBN â†’ LH circuit is activated by noxious stimuli. Interestingly, either activation or inhibition of this circuit induced analgesia. Optogenetic activation of LPBN afferents in the LH elicited spontaneous jumping and induced place aversion. Optogenetic inhibition inhibited jumping behavior to noxious heat. Ablation of LH glutamatergic neurons could abolish light-evoked analgesia and jumping behavior. Our study revealed a role for the LPBN â†’ LH pathway in nocifensive behaviors.

Membrane phospholipid peroxidation promotes loss of dopaminergic neurons in psychological stress-induced Parkinson's disease susceptibility.

Parkinson's disease (PD) is a neurodegenerative disorder associated with α-synuclein aggregation and dopaminergic neuron loss in the midbrain. There is evidence that psychological stress promotes PD progression by enhancing glucocorticoids-related oxidative damage, however, the mechanisms involved are unknown. The present study demonstrated that plasma membrane phospholipid peroxides, as determined by phospholipidomics, triggered ferroptosis in dopaminergic neurons, which in turn contributed to stress exacerbated PD-like motor disorder in mice overexpressing mutant human α-synuclein. Using hormonomics, we identified that stress stimulated corticosteroid release and promoted 15-lipoxygenase-1 (ALOX15)-mediated phospholipid peroxidation. ALOX15 was upregulated by α-synuclein overexpression and acted as a fundamental risk factor in the development of chronic stress-induced parkinsonism and neurodegeneration. Further, we demonstrated the mechanism by which corticosteroids activated the PKC pathway and induced phosphatidylethanolamine-binding protein-1 (PEBP1) to form a complex with ALOX15, thereby facilitating ALOX15 to locate on the plasma membrane phospholipids. A natural product isolated from herbs, leonurine, was screened with activities of inhibiting the ALOX15/PEBP1 interaction and thereby attenuating membrane phospholipid peroxidation. Collectively, our findings demonstrate that stress increases the susceptibility of PD by driving membrane lipid peroxidation of dopaminergic neurons and suggest the ALOX15/PEBP1 complex as a potential intervention target.

Choroidal vasculature act as predictive biomarkers of long-term ocular elongation in myopic children treated with orthokeratology: a prospective cohort study.

BACKGROUND: Despite receiving orthokeratology (ortho-k), the efficacy of retarding ocular elongation during myopia varies among myopic children. The current study aimed to investigate the early changes of choroidal vasculature at one month after ortho-k treatment and its association with one-year ocular elongation, as well as the role of such choroidal responses in predicting the one-year control efficacy of ortho-k treatment. METHODS: A prospective cohort study was conducted in myopic children treated with ortho-k. Myopic children aged between 8 and 12 years who were willing to wear ortho-k lenses were recruited consecutively from the Eye Hospital of Wenzhou Medical University. Subfoveal choroidal thickness (SFCT), submacular total choroidal luminal area (LA), stromal area (SA), choroidal vascularity index (CVI), choriocapillaris flow deficit (CcFD) were evaluated by optical coherence tomography (OCT) and OCT angiography over a one-year period. RESULTS: Fifty eyes from 50 participants (24 males) who finished one-year follow-ups as scheduled were included, with a mean age of 10.31 ± 1.45 years. The one-year ocular elongation was 0.19 ± 0.17 mm. The LA (0.03 ± 0.07 mm2), SA (0.02 ± 0.05 mm2) increased proportionally after one-month of ortho-k wear (both P < 0.01), as did the SFCT (10.62 ± 19.98 µm, P < 0.001). Multivariable linear regression analyses showed that baseline CVI (ß = - 0.023 mm/1%, 95% CI: - 0.036 to - 0.010), one-month LA change (ß = - 0.009 mm/0.01 mm2, 95% CI: - 0.014 to - 0.003), one-month SFCT change (ß = - 0.035 mm/10 µm, 95% CI: - 0.053 to - 0.017) were independently associated with one-year ocular elongation during ortho-k treatment after adjusting with age and sex (all P < 0.01). The area under the receiver operating characteristic curve of prediction model including baseline CVI, one-month SFCT change, age, and sex achieved 0.872 (95% CI: 0.771 to 0.973) for discriminating children with slow or fast ocular elongation. CONCLUSIONS: Choroidal vasculature is associated with ocular elongation during ortho-k treatment. Ortho-k treatment induces increases in choroidal vascularity and choroidal thickness as early as one month. Such early changes can act as predictive biomarkers of myopia control efficacy over a long term. The utilization of these biomarkers may help clinicians identify children who can benefit from ortho-k treatment, and thus has critical implications for the management strategies towards myopia control.

ALOX5 inhibition protects against dopaminergic neurons undergoing ferroptosis.

Oxidative disruption of dopaminergic neurons is regarded as a crucial pathogenesis in Parkinson's disease (PD), eventually causing neurodegenerative progression. (-)-Clausenamide (Clau) is an alkaloid isolated from plant Clausena lansium (Lour.), which is well-known as a scavenger of lipid peroxide products and exhibiting neuroprotective activities both in vivo and in vitro, yet with the in-depth molecular mechanism unrevealed. In this study, we evaluated the protective effects and mechanisms of Clau on dopaminergic neuron. Our results showed that Clau directly interacted with the Ser663 of ALOX5, the PKCα-phosphorylation site, and thus prevented the nuclear translocation of ALOX5, which was essential for catalyzing the production of toxic lipids 5-HETE. LC-MS/MS-based phospholipidomics analysis demonstrated that the oxidized membrane lipids were involved in triggering ferroptotic death in dopaminergic neurons. Furthermore, the inhibition of ALOX5 was found to significantly improving behavioral defects in PD mouse model, which was confirmed associated with the effects of attenuating the accumulation of lipid peroxides and neuronal damages. Collectively, our findings provide an attractive strategy for PD therapy by targeting ALOX5 and preventing ferroptosis in dopaminergic neurons.

Radiomics approach with deep learning for predicting T4 obstructive colorectal cancer using CT image.

OBJECTIVES: Patients with T4 obstructive colorectal cancer (OCC) have a high mortality rate. Therefore, an accurate distinction between T4 and T1-T3 (NT4) in OCC is an important part of preoperative evaluation, especially in the emergency setting. This paper introduces three models of radiomics, deep learning, and deep learning-based radiomics to identify T4 OCC. METHODS: We established a dataset of computed tomography (CT) images of 164 patients with pathologically confirmed OCC, from which 2537 slides were extracted. First, since T4 tumors penetrate the bowel wall and involve adjacent organs, we explored whether the peritumoral region contributes to the assessment of T4 OCC. Furthermore, we visualized the radiomics and deep learning features using the t-distributed stochastic neighbor embedding technique (t-SNE). Finally, we built a merged model by fusing radiomic features with deep learning features. In this experiment, the performance of each model was evaluated by the area under the receiver operating characteristic curve (AUC). RESULTS: In the test cohort, the AUC values predicted by the radiomics model in the dilated region of interest (dROI) was 0.770. And the AUC value of the deep learning model with the patches extended 20-pixel reached 0.936. Combining the characteristics of radiomics and deep learning, our method achieved an AUC value of 0.947 in the T4 and non-T4 (NT4) classification, and increased the AUC value to 0.950 after the addition of clinical features. CONCLUSION: The prediction results of our merged model of deep learning radiomics outperformed the deep learning model and significantly outperformed the radiomics model. The experimental results demonstrate that combining the peritumoral region improves the prediction performance of the radiomics model and the deep learning model.

Tyrosine-Conjugation Method for Evaluating BACE1 Activity Based on Silver Nanoparticles/Metal-Organic Framework Composites as Electrochemical Tags.

Beta-site secretase (BACE1) catalyzes the cleavage of amyloid precursor protein (APP), which process ultimately lead to plaque deposition in the brain of Alzheimer's disease (AD). Thus, accurate monitor of BACE1 activity is essential to screen inhibitors for AD treatment. This study develops a sensitive electrochemical assay for probing BACE1 activity based on silver nanoparticles (AgNPs) and tyrosine conjugation as tags and a marking method, respectively. An APP segment is firstly immobilized on aminated microplate reactor. Cytosine (C) rich sequence-templated AgNPs/Zr-based metal-organic framework (MOF) composite is modified by phenol groups, and then the prepared tag (ph-AgNPs@MOF) is captured in microplate surface by the conjugation reaction of phenolic groups between tyrosine and tag. After cleavage by BACE1, the solution containing ph-AgNPs@MOF tags is transferred to the screen-printed graphene electrode (SPGE) surface for voltammetric detection of AgNP signal. This sensitive detection for BACE1 provided an excellent linear relationship between 1 to 200 pM with a detection limit of 0.8 pM. Furthermore, this electrochemical assay is successfully applied for screening of BACE1 inhibitors. This strategy is also verified to be used for evaluation of BACE1 in serum samples.

Balancing activation and co-stimulation of CAR tunes signaling dynamics and enhances therapeutic potency.

CD19-targeting chimeric antigen receptors (CARs) with CD28 and CD3ζ signaling domains have been approved by the US FDA for treating B cell malignancies. Mutation of immunoreceptor tyrosine-based activation motifs (ITAMs) in CD3ζ generated a single-ITAM containing 1XX CAR, which displayed superior antitumor activity in a leukemia mouse model. Here, we investigated whether the 1XX design could enhance therapeutic potency against solid tumors. We constructed both CD19- and AXL-specific 1XX CARs and compared their in vitro and in vivo functions with their wild-type (WT) counterparts. 1XX CARs showed better antitumor efficacy in both pancreatic and melanoma mouse models. Detailed analysis revealed that 1XX CAR-T cells persisted longer in vivo and had a higher percentage of central memory cells. With fluorescence resonance energy transfer (FRET)-based biosensors, we found that decreased ITAM numbers in 1XX resulted in similar 70-kDa zeta chain-associated protein (ZAP70) activation, while 1XX induced higher Ca2+ elevation and faster extracellular signal-regulated kinase (Erk) activation than WT CAR. Thus, our results confirmed the superiority of 1XX against two targets in different solid tumor models and shed light on the underlying molecular mechanism of CAR signaling, paving the way for the clinical applications of 1XX CARs against solid tumors.

Effects of Broussonetia papyrifera (L.) L'Hér. ex Vent. fruits water extract on hippocampal neurogenesis in the treatment of APP/PS1 transgenic mice.

Background: Adult neurogenesis plays an important role in repairing damaged neurons and improving cognitive impairment in Alzheimer's disease (AD). B. Papyrifera (L.) L'Hér. ex Vent. fruits (BL), a traditional Chinese medicine for tonifying the kidney, has been reported to improve cognitive function in AD mice, but the underlying mechanisms have not been clearly illuminated. This study aimed to provide an overview of the differential compounds in the brain of APP/PS1 mice after BL water extract (BLWE) treatment through metabolomics technology and to elucidate whether the therapeutic effect and mechanism are through the enhancement of neurogenesis. Methods: APP/PS1 transgenic mice were treated with different doses of BLWE. After 6 weeks of intragastric injection, the therapeutic effects of BLWE on APP/PS1 transgenic mice were determined by the Morris water maze test, immunohistochemistry, hematoxylin & eosin and Nissl staining, enzyme-linked immunosorbent assay and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Subsequently, metabolomics technology was used to analyze the regulatory effect of BLWE on differential compounds in the brain of APP/PS1 mice, and on this basis, its molecular mechanism of BLWE was screened. Finally, the protein expression of the Wnt/ß-catenin signaling pathway was detected by Western blotting. Results: After BLWE treatment, the learning and memory function of APP/PS1 mice were significantly improved, which was related to the increase in the number of Nestin+/BrdU+ and NeuN+/BrdU+ cells, and the decrease in the number of apoptotic cells in the hippocampus. BLWE treatment could also up-regulate the expression of synapse-associated proteins. Moreover, BLWE could modulate endogenous metabolic compounds in the brains of AD mice, including N-acetyl-aspartate, glutamine, etc. Furthermore, BLWE inhibited the phosphorylation of Tyr216-GSK-3ß and ß-catenin protein while increased CyclinD1 protein expression. Conclusion: We demonstrated that BLWE can enhance neural stem cells proliferation and improve neurogenesis, thereby efficiently repairing damaged neurons in the hippocampus and ameliorating cognitive impairment in APP/PS1 transgenic mice. The mechanism is at least partly through activating the Wnt/ß-catenin signaling pathway.

A Lower False Positive Pulmonary Nodule Detection Approach for Early Lung Cancer Screening.

Pulmonary nodule detection with low-dose computed tomography (LDCT) is indispensable in early lung cancer screening. Although existing methods have achieved excellent detection sensitivity, nodule detection still faces challenges such as nodule size variation and uneven distribution, as well as excessive nodule-like false positive candidates in the detection results. We propose a novel two-stage nodule detection (TSND) method. In the first stage, a multi-scale feature detection network (MSFD-Net) is designed to generate nodule candidates. This includes a proposed feature extraction network to learn the multi-scale feature representation of candidates. In the second stage, a candidate scoring network (CS-Net) is built to estimate the score of candidate patches to realize false positive reduction (FPR). Finally, we develop an end-to-end nodule computer-aided detection (CAD) system based on the proposed TSND for LDCT scans. Experimental results on the LUNA16 dataset show that our proposed TSND obtained an excellent average sensitivity of 90.59% at seven predefined false positives (FPs) points: 0.125, 0.25, 0.5, 1, 2, 4, and 8 FPs per scan on the FROC curve introduced in LUNA16. Moreover, comparative experiments indicate that our CS-Net can effectively suppress false positives and improve the detection performance of TSND.

The effect of superfine grinding on physicochemical properties of three kinds of mushroom powder.

The effects of superfine grinding on apparent structure, physicochemical properties, and functional characteristics of three kinds of mushroom (Lentinus edodes, Hericium erinaceus, and Cordyceps militaris) powders were investigated. Coarse and 100-mesh powders of the mushrooms were prepared by common grinding, while a superfine powder was obtained by superfine grinding. By comparing the mushrooms before and after grinding, it was found that the mushroom fines did not produce new chemical groups but increased crystallinity. The results of the physicochemical properties revealed that the fines became less fluid after grinding. The protein content and solubility increased as the particle size decreased. The water and oil holding capacity, glucose binding capacity, cation exchange capacity, and antioxidant activity of the mushroom fines increased after grinding. This study provides a theoretical basis for the development process of edible mushroom food, as well as new ideas for the development of edible mushrooms.

Automatic upper airway segmentation in static and dynamic MRI via anatomy-guided convolutional neural networks.

PURPOSE: Upper airway segmentation on MR images is a prerequisite step for quantitatively studying the anatomical structure and function of the upper airway and surrounding tissues. However, the complex variability of intensity and shape of anatomical structures and different modes of image acquisition commonly used in this application makes automatic upper airway segmentation challenging. In this paper, we develop and test a comprehensive deep learning-based segmentation system for use on MR images to address this problem. MATERIALS AND METHODS: In our study, both static and dynamic MRI data sets are utilized, including 58 axial static 3D MRI studies, 22 mid-retropalatal dynamic 2D MRI studies, 21 mid-retroglossal dynamic 2D MRI studies, 36 mid-sagittal dynamic 2D MRI studies, and 23 isotropic dynamic 3D MRI studies, involving a total of 160 subjects and over 20 000 MRI slices. Samples of static and 2D dynamic MRI data sets were randomly divided into training, validation, and test sets by an approximate ratio of 5:2:3. Considering that the variability of annotation data among 3D dynamic MRIs was greater than for other MRI data sets, we increased the ratio of training data for these data to improve the robustness of the model. We designed a unified framework consisting of the following procedures. For static MRI, a generalized region-of-interest (GROI) strategy is applied to localize the partitions of nasal cavity and other portions of upper airway in axial data sets as two separate subobjects. Subsequently, the two subobjects are segmented by two separate 2D U-Nets. The two segmentation results are combined as the whole upper airway structure. The GROI strategy is also applied to other MRI modes. To minimize false-positive and false-negative rates in the segmentation results, we employed a novel loss function based explicitly on these rates to train the segmentation networks. An inter-reader study is conducted to test the performance of our system in comparison to human variability in ground truth (GT) segmentation of these challenging structures. RESULTS: The proposed approach yielded mean Dice coefficients of 0.84±0.03, 0.89±0.13, 0.84±0.07, and 0.86±0.05 for static 3D MRI, mid-retropalatal/mid-retroglossal 2D dynamic MRI, mid-sagittal 2D dynamic MRI, and isotropic dynamic 3D MRI, respectively. The quantitative results show excellent agreement with manual delineation results. The inter-reader study results demonstrate that the segmentation performance of our approach is statistically indistinguishable from manual segmentations considering the inter-reader variability in GT. CONCLUSIONS: The proposed method can be utilized for routine upper airway segmentation from static and dynamic MR images with high accuracy and efficiency. The proposed approach has the potential to be employed in other dynamic MRI-related applications, such as lung or heart segmentation.

Objective comparison of methods to decode anomalous diffusion.

Deviations from Brownian motion leading to anomalous diffusion are found in transport dynamics from quantum physics to life sciences. The characterization of anomalous diffusion from the measurement of an individual trajectory is a challenging task, which traditionally relies on calculating the trajectory mean squared displacement. However, this approach breaks down for cases of practical interest, e.g., short or noisy trajectories, heterogeneous behaviour, or non-ergodic processes. Recently, several new approaches have been proposed, mostly building on the ongoing machine-learning revolution. To perform an objective comparison of methods, we gathered the community and organized an open competition, the Anomalous Diffusion challenge (AnDi). Participating teams applied their algorithms to a commonly-defined dataset including diverse conditions. Although no single method performed best across all scenarios, machine-learning-based approaches achieved superior performance for all tasks. The discussion of the challenge results provides practical advice for users and a benchmark for developers.

A novel polysaccharide obtained from Siraitia grosvenorii alleviates inflammatory responses in a diabetic nephropathy mouse model via the TLR4-NF-κB pathway.

The inflammatory and antioxidant effects of a novel Siraitia grosvenorii polysaccharide (SGP-1-1) were investigated in an inflammation-suppressed diabetic nephropathy (DN) mouse model, and the underlying molecular mechanisms of inflammation and oxidative stress in SGP-1-1-treated mouse models were elucidated. The results demonstrated that DN mouse models treated with SGP-1-1 (50, 100, and 200 mg kg-1 d-1) exhibited good inflammation-modulating activity. In addition, histopathological analysis showed that glomerular atrophy, severe glomerular thylakoid hyperplasia, tubular endothelial detachment, basement membrane exposure, cytoplasmic infiltration with inflammatory cells, and interstitial oedema were all alleviated in DN mice after treatment with SGP-1-1. Metabolomics analysis based on UPLC-Q-TOF/MS revealed that a close relationship between the occurrence of DN and the potential 39 biomarkers, especially, leukotriene E3 and arachidonic acid,of which the main invloved metabolic pathways may beglycerophospholipid metabolism, arachidonic acid metabolism and primary bile acid biosynthesis. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis results demonstrated that SGP-1-1 downregulates mRNA and the protein expression of the G protein-coupled cell membrane receptor TLR4 and its downstream protein kinase (NF-κB p65). This, resulted in the inhibition of the TLR4-NF-κB pathway in the peritoneum of DN mice by regulating inflammation, while stimulating the production of superoxide dismutase (SOD) and reducing the production of cytokine (IL-6, TNF-α) and malondialdehyde (MDA).

Pentiptycene-based ladder polymers with configurational free volume for enhanced gas separation performance and physical aging resistance.

Polymers of intrinsic microporosity (PIMs) have shown promise in pushing the limits of gas separation membranes, recently redefining upper bounds for a variety of gas pair separations. However, many of these membranes still suffer from reductions in permeability over time, removing the primary advantage of this class of polymer. In this work, a series of pentiptycene-based PIMs incorporated into copolymers with PIM-1 are examined to identify fundamental structure-property relationships between the configuration of the pentiptycene backbone and its accompanying linear or branched substituent group. The incorporation of pentiptycene provides a route to instill a more permanent, configuration-based free volume, resistant to physical aging via traditional collapse of conformation-based free volume. PPIM-ip-C and PPIM-np-S, copolymers with C- and S-shape backbones and branched isopropoxy and linear n-propoxy substituent groups, respectively, each exhibited initial separation performance enhancements relative to PIM-1. Additionally, aging-enhanced gas permeabilities were observed, a stark departure from the typical permeability losses pure PIM-1 experiences with aging. Mixed-gas separation data showed enhanced CO2/CH4 selectivity relative to the pure-gas permeation results, with only ∼20% decreases in selectivity when moving from a CO2 partial pressure of ∼2.4 to ∼7.1 atm (atmospheric pressure) when utilizing a mixed-gas CO2/CH4 feed stream. These results highlight the potential of pentiptycene's intrinsic, configurational free volume for simultaneously delivering size-sieving above the 2008 upper bound, along with exceptional resistance to physical aging that often plagues high free volume PIMs.

Comparisons of the anti-inflammatory, antiviral, and hemostatic activities and chemical profiles of raw and charred Schizonepetae Spica.

ETHNOPHARMACOLOGICAL RELEVANCE: A common view in traditional Chinese medicine (TCM) theory is that "processing can alter the efficacy of crude drugs". The clinical usage of some processed products may have already changed greatly over time during the development of modern scientific analysis. Therefore, the view of "processing can alter the efficacy of crude drugs" should be confirmed by comparative studies. Schizonepetae Spica (SS), a Chinese medicinal herb, is the dried spike of Schizonepeta tenuifolia Briq. It is available in two forms: raw products and charred products (Schizonepetae Spica Carbonisata, SSC; raw SS processed by stir-frying until carbonization). Raw SS is commonly used to treat TCM symptoms that resemble common cold, fever, respiratory tract infection and allergic dermatitis, while SSC has long been used as a remedy for TCM symptoms that resemble bloody stool and metrorrhagia. AIM OF THE STUDY: We aimed to examine whether stir-fry processing alters the anti-inflammatory, antiviral and hemostatic activities of SS and explore the chemical profile behind the potential changes in medicinal properties caused by stir-fry processing. MATERIALS AND METHODS: We used cell models to examine the anti-inflammatory and antiviral effects of raw SS and SSC. The bleeding time of the tail bleeding model and clotting time of the capillary method in mice were used to compare the hemostasis properties of raw SS and SSC. The chemical profiles of SS and SSC were compared using a method combining gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (HPLC/Q-TOF-MS) analysis. RESULTS: The anti-inflammatory effects of SSC were less potent than those of raw SS. Both raw SS and SSC effectively inhibited viral infection in a dose-dependent manner, with IC50 values of 96.30 and 9.73 µg/mL and selectivity index (SI) values of >1.56 and 7.78, respectively. Interestingly, SSC showed more potent antiviral activities than raw SS. Intragastric administration of raw SS and SSC to mice demonstrated that the hemostatic effects of SSC were more potent than those of raw SS. By comparing the volatile chemical profiles of SSC, we found that twenty-nine constituents disappeared and that fifty-four new constituents were formed while the relative contents of five other components decreased and three other components increased. Additionally, the nonvolatile chemical profiles of raw SS and SSC differed, with thirty-two lower peaks and seven higher peaks in SSC than in SS. CONCLUSION: Our study showed that raw SS and SSC support traditional practice for the clinical applications of these two products except for raw SS used for the treatment of viral infection. It is a fascinating challenge to form SSCs with both traditional hemostatic activities and antiviral properties after stir-fry processing. In addition, the volatile and nonvolatile chemical constituents of raw SS changed dramatically during processing. Further studies are warranted to explore whether the change in chemical constituents is in accordance with the purpose of processing.