Structure-guided discovery of protein and glycan components in native mastigonemes.

Mastigonemes, the hair-like lateral appendages lining cilia or flagella, participate in mechanosensation and cellular motion, but their constituents and structure have remained unclear. Here, we report the cryo-EM structure of native mastigonemes isolated from Chlamydomonas at 3.0 Å resolution. The long stem assembles as a super spiral, with each helical turn comprising four pairs of anti-parallel mastigoneme-like protein 1 (Mst1). A large array of arabinoglycans, which represents a common class of glycosylation in plants and algae, is resolved surrounding the type II poly-hydroxyproline (Hyp) helix in Mst1. The EM map unveils a mastigoneme axial protein (Mstax) that is rich in heavily glycosylated Hyp and contains a PKD2-like transmembrane domain (TMD). Mstax, with nearly 8,000 residues spanning from the intracellular region to the distal end of the mastigoneme, provides the framework for Mst1 assembly. Our study provides insights into the complexity of protein and glycan interactions in native bio-architectures.

Fundamental Structural and Electronic Understanding of Palladium Catalysts on Nitride and Oxide Supports.

The nature of the support can fundamentally affect the function of a heterogeneous catalyst. For the novel type of isolated metal atom catalysts, sometimes referred to as single-atom catalysts, systematic correlations are still rare. Here, we report a general finding that Pd on nitride supports (non-metal and metal nitride) features a higher oxidation state compared to that on oxide supports (non-metal and metal oxide). Through thorough oxidation state investigations by X-ray absorption spectroscopy (XAS), X-ray photoelectron spectroscopy (XPS), CO-DRIFTS, and density functional theory (DFT) coupled with Bader charge analysis, it is found that Pd atoms prefer to interact with surface hydroxyl group to form a Pd(OH)x species on oxide supports, while on nitride supports, Pd atoms incorporate into the surface structure in the form of Pd-N bonds. Moreover, a correlation was built between the formal oxidation state and computational Bader charge, based on the periodic trend in electronegativity.

Transient Receptor Potential Melastatin 7 (TRPM7) Ion Channel Inhibitors: Preliminary SAR and Conformational Studies of Xenicane Diterpenoids from the Hawaiian Soft Coral Sarcothelia edmondsoni.

Waixenicin A, a xenicane diterpene from the octocoral Sarcothelia edmondsoni, is a selective, potent inhibitor of the TRPM7 ion channel. To study the structure-activity relationship (SAR) of waixenicin A, we isolated and assayed related diterpenes from S. edmondsoni. In addition to known waixenicins A (1) and B (2), we purified six xenicane diterpenes, 7S,8S-epoxywaixenicins A (3) and B (4), 12-deacetylwaixenicin A (5), waixenicin E (6), waixenicin F (7), and 20-acetoxyxeniafaraunol B (8). We elucidated the structures of 3-8 by NMR and MS analyses. Compounds 1, 2, 3, 4, and 6 inhibited TRPM7 activity in a cell-based assay, while 5, 7, and 8 were inactive. A preliminary SAR emerged showing that alterations to the nine-membered ring of 1 did not reduce activity, while the 12-acetoxy group, in combination with the dihydropyran, appears to be necessary for TRPM7 inhibition. The bioactive compounds are proposed to be latent electrophiles by formation of a conjugated oxocarbenium ion intermediate. Whole-cell patch-clamp experiments demonstrated that waixenicin A inhibition is irreversible, consistent with a covalent inhibitor, and showed nanomolar potency for waixenicin B (2). Conformational analysis (DFT) of 1, 3, 7, and 8 revealed insights into the conformation of waixenicin A and congeners and provided information regarding the stabilization of the proposed pharmacophore.

Study of Canine Distemper Virus Presence in Catalonia's Wild Carnivores through H Gene Amplification and Sequencing.

Canine distemper virus (CDV) is recognised worldwide as an important pathogen in both domestic and wild carnivores. Few data are available on its impact and spread on the wildlife/wildlife-domestic animal-environment interface. This study, aimed at developing a conservation-oriented control strategy, analysed 89 sick or deceased animals from 2019 to 2023 at the Wildlife Rehabilitation Centre in Torreferrussa. RT-PCR and sequencing of the partial H gene were used to detect and analyse CDV in tissues. The total positive percentage was 20.22% (18/89), comprising 13 red foxes (44.8%), 4 European badgers (28.6%), and 1 American mink (4.5%), while 24 Eurasian otters tested negative. Phylogenetic analysis indicated that all of the CDV strains belong to the European lineage. Geographically distant individuals and different species shared the same viral strain, suggesting a strong capacity of CDV for interspecies and long-distance transmission. This calls for further research, particularly focusing on potential impacts of CDV on endangered carnivores.

Laser-Induced Electron Synchronization Excitation for Photochemical Synthesis and Patterning Graphene-Based Electrode.

Micro-supercapacitors (MSCs) represent a pressing requirement for powering the forthcoming generation of micro-electronic devices. The simultaneous realization of high-efficiency synthesis of electrode materials and precision patterning for MSCs in a single step presents an ardent need, yet it poses a formidable challenge. Herein, a unique shaped laser-induced patterned electron synchronization excitation strategy has been put forward to photochemical synthesis RuO2 /reduced graphene oxide (rGO) electrode and simultaneously manufacture the micron-scale high-performance MSCs with ultra-high resolution. Significantly, the technique represents a noteworthy advancement over traditional laser direct writing (LDW) patterning and photoinduced synthetic electrode methods. It not only improves the processing efficiency for MSCs and the controllability of laser-induced electrode material but also enhances electric fields and potentials at the interface for better electrochemical performance. The resultant MSCs exhibit excellent area and volumetric capacitance (516 mF cm-2 and 1720 F cm-3 ), and ultrahigh energy density (0.41 Wh cm-3 ) and well-cycle stability (retaining 95% capacitance after 12000 cycles). This investigation establishes a novel avenue for electrode design and underscores substantial potential in the fabrication of diverse microelectronic devices.

System inflammation response index: a novel inflammatory indicator to predict all-cause and cardiovascular disease mortality in the obese population.

AIM: This study aims to investigate the relationship between two novel inflammatory markers, namely, the Systemic Inflammatory Response Index (SIRI) and the Systemic Immune Inflammatory Index (SII), as well as the all-cause and cardiovascular disease (CVD) mortality in the obese population. MATERIALS AND METHODS: We conducted a prospective cohort study based on the data of 13,026 obese adults (age ≥ 18 years) from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014 and followed until December 2019. SIRI was calculated by the formula: (neutrophil count × monocyte count) / lymphocyte count, while that of SII was: (platelet count × neutrophil count)/lymphocyte count. The association of SIRI and SII with all-cause and CVD mortality was evaluated using Cox regression. In addition, the nomogram was performed to predict 10-year survival probability. RESULTS: During a median follow-up of 137 months, 1959 and 553 all-cause and CVD deaths were recorded, respectively. Spearman correlation analysis indicated that SIRI and SII were unrelated to almost all baseline characteristics (r < 0.15). Multivariate Cox regression models displayed that each standard deviation (SD) increase in SIRI was associated with a 16% (HR 1.16; 95% CI 1.09-1.24) and 22% (HR 1.22; 95% CI 1.10-1.36) increase in the risk of all-cause and CVD mortality, respectively. Likewise, every SD increase in SII was correlated with a 9% (HR 1.09; 95% CI 1.02-1.16) and 14% (HR 1.14; 95% CI 1.04-1.26) increase in the risk of all-cause and CVD mortality, respectively. The predictive value of SIRI for all-cause and CVD mortality (AUC = 0.601 and 0.624) exceeded that of SII (AUC = 0.528 and 0.539). Moreover, the nomogram displayed a substantial predictive value for 10-year survival (AUC = 0.847) with sensitivity and specificity exceeding 75%. CONCLUSIONS: In the obese population, SIRI and SII are independent risk factors for all-cause and CVD mortality. Notably, the predictive ability of SIRI for both all-cause and CVD mortality significantly outperforms that of SII, suggesting that SIRI is a more valuable marker of inflammation.

Treatment strategies and drug resistance mechanisms in adenocarcinoma of different organs.

Adenocarcinoma is a common type of malignant tumor, originating from glandular epithelial cells in various organs, such as pancreas, breast, lung, stomach, colon, rectus, and prostate. For patients who lose the opportunity for radical surgery, medication is available to provide potential clinical benefits. However, drug resistance is a big obstacle to obtain desired clinical prognosis. In this review, we provide a summary of treatment strategies and drug resistance mechanisms in adenocarcinoma of different organs, including pancreatic cancer, gastric adenocarcinoma, colorectal adenocarcinoma, lung adenocarcinoma, and prostate cancer. Although the underlying molecular mechanisms involved in drug resistance of adenocarcinoma vary from one organ to the other, there are several targets that are universal for drug resistance in adenocarcinoma, and targeting these molecules could potentially reverse drug resistance in the treatment of adenocarcinomas.

Multifunctional CuFe2O4@HA as a GSH-depleting nanoplatform for targeted photothermal/enhanced-chemodynamic synergistic therapy.

Chemodynamic therapy (CDT), which converts overexpressed hydrogen peroxide (H2O2) in tumor cells to hydroxyl radicals (•OH) by Fenton reactions, is considered a prospective strategy in anticancer therapy. However, the high level of glutathione (GSH) and poor Fenton catalytic efficiency contribute to the suboptimal efficiency of CDT. Herein, we present a multifunctional nanoplatform (CuFe2O4@HA) that can induce GSH depletion and combine with photothermal therapy (PTT) to enhance antitumor efficacy. CuFe2O4@HA nanoparticles could release Cu2+ and Fe3+ after entering tumor cells by targeting hyaluronic acid (HA). Subsequently, Cu2+ and Fe3+ were reduced to Cu+ and Fe2+ by GSH, where Cu+/Fe2+ significantly catalyzed H2O2 to produce a higher level of •OH, and the depletion of GSH disrupted the antioxidant capacity of the tumor. Therefore, depleting GSH substantially enhances the level of •OH in tumor cells. In addition, CuFe2O4@HA nanoparticles have considerable absorption in the near-infrared (NIR) region, which can stimulate excellent PTT effects. More importantly, the heat generated by PTT can further enhance the Fenton catalysis efficiency. In vitro and in vivo experiments have demonstrated the excellent tumor-killing effect of CuFe2O4@HA nanoparticles. This strategy overcomes the problem of insufficient CDT efficacy caused by GSH overexpression and poor catalytic efficiency. Moreover, this versatile nanoplatform provides a reference for self-enhanced CDT and PTT/CDT synergistic targeted therapy.

Effects of regular aerobic exercise on vascular function in overweight or obese older adults: A systematic review and meta-analysis.

Background: Overweight and obese older adults have a high risk for developing cardiovascular disease. Aerobic exercise is a valuable strategy to improve vascular health, but the effects of aerobic exercise on vascular endothelial function in obese and overweight older adults remain controversial. The purpose of this meta-analysis was to investigate the effects of aerobic exercise on vascular function in obese and overweight older adults with or without comorbidity. Methods: A systematic literature search for related studies published in English was conducted between January 1989 and October 30, 2022, in the PubMed, Embase, and Cochrane Library databases. A random effects model was chosen for meta-analysis, which calculated the effect sizes of control and intervention groups after exercise intervention using standardized mean differences (SMDs) corrected for Hedges' g bias and 95% confidence intervals (95% CIs). Results: Twenty-six studies containing 1418 participants were included in the study. After excluding three studies contributing to higher heterogeneity by sensitivity analysis, there are small effects of regular aerobic exercise on vascular function of obese and overweight older adults, including flow-mediated dilation (FMD) [SMD = 0.21, 95% CI (0.02, 0.41), z = 2.16, df = 19, I2 = 52.2%, P = 0.031] and pulse wave velocity (PWV) [SMD = -0.24, 95% CI (-0.46, -0.02), z = 2.17, df = 10, I2 = 8.6%, P = 0.030], and no significant effect was observed on augmentation index (Aix). Subgroup analysis showed small effects of regular aerobic exercise on FMD [SMD = 0.37, 95% CI (0.13, 0.61), z = 3.05, df = 9, I2 = 52.6%, P = 0.002] in the overweight not obese subgroup (25 = BMI <30 kg/m2), but no significant effect on the obese subgroup (BMI ≥30 kg/m2). Regular aerobic exercise for more than 24 weeks improved FMD by small effect sizes [SMD = 0.48, 95% CI (0.04, 0.93), z = 2.12, df = 5, I2 = 56.4%, P = 0.034] and for more than three times per week improved FMD by moderate effect sizes [SMD = 0.55, 95% CI (0.12, 0.98), z = 2.50, df = 3, I2 = 31.1%, P = 0.012] in obese and overweight older adults with or without CVD. Conclusion: In obese and overweight older adults with or without comorbidity, regular aerobic exercise for more than 24 weeks improved FMD by small effect sizes and exercise for more than three times per week improved FMD by moderate effect sizes and regular aerobic exercise reduced PWV by small effect sizes and had no influence on Aix. Taken together, it was recommended that obese and overweight older adults should adhere to regular aerobic exercise, training at least 3 times per week for better results.

Molecular basis for substrate recognition and transport of human GABA transporter GAT1.

γ-Aminobutyric acid (GABA), an important inhibitory neurotransmitter in the central nervous system, is recycled through specific GABA transporters (GATs). GAT1, which is mainly expressed in the presynaptic terminals of axons, is a potential drug target of neurological disorders due to its essential role in GABA transport. Here we report four cryogenic electron microscopy structures of human GAT1, at resolutions of 2.2-3.2 Å. GAT1 in substrate-free form or in complex with the antiepileptic drug tiagabine exhibits an inward-open conformation. In the presence of GABA or nipecotic acid, inward-occluded structures are captured. The GABA-bound structure reveals an interaction network bridged by hydrogen bonds and ion coordination for GABA recognition. The substrate-free structure unwinds the last helical turn of transmembrane helix TM1a to release sodium ions and substrate. Complemented by structure-guided biochemical analyses, our studies reveal detailed mechanism of GABA recognition and transport, and elucidate mode of action of the inhibitors, nipecotic acid and tiagabine.

Association of lifestyle habits and cardiovascular risk among sedentary adults.

This study aimed to analyze the association of lifestyle habits (physical activity, sleep habits, and eating habits) with cardiovascular risk (arterial stiffness and autonomic nervous system function) among sedentary adults. Sixty adults of sedentariness and physical activity were evaluated by accelerometers; sleep and eating habits were assessed by questionnaires; cardiovascular risks were assessed by pulse wave velocity (PWV), ankle-brachial index, flow mediated dilation, and heart rate variability; circulating biomarkers were also determined. Prolonged sitting (represented by longer maximum length of sedentary bouts, lower length of sedentary breaks, and more total time of sitting) were (P < .05) significantly associated with matrix metalloproteinases, neuropeptide Y, C-reactive protein, peptide Y, ghrelin, and leptin; significant associations (P < .05) were also observed of total time in physical activity with most circulating biomarkers except interleukin-6, tumor necrosis factor-α, and adiponectin. Sleep habits, especially sleep efficiency, were (P < .05) significantly associated with PWV, ankle-brachial index, and circulating biomarkers. Eating habits (including emotional overeating and enjoyment of food) were (P < .05) significantly associated with PWVs and flow mediated dilation; satiety responsiveness and enjoyment of food were (P < .05) significantly associated with low-frequency spectral component expressed in normalized units, high frequency spectral component expressed in normalized units, and ratio between low-frequency/high frequency spectral component expressed in normalized units. The findings indicated that several lifestyle habits among sedentary adults were closely associated with increased cardiovascular risk. Sedentary people were encouraged to live with sufficient physical activity, good sleep, and healthy eating habits for decreasing arterial stiffness and balancing autonomic nervous function.

Induction of filopodia formation by α-Actinin-2 via RelA with a feedforward activation loop promoting overt bone marrow metastasis of gastric cancer.

BACKGROUND: Bone marrow metastasis (BMM) is underestimated in gastric cancer (GC). GC with BMM frequently complicate critical hematological abnormalities like diffused intravascular coagulation and microangiopathic hemolytic anemia, which constitute a highly aggressive GC (HAGC) subtype. HAGC present a very poor prognosis with peculiar clinical and pathological features when compared with not otherwise specified advanced GC (NAGC). But the molecular mechanisms underlying BMM from GC remain rudimentary. METHODS: The transcriptomic difference between HAGC and NAGC were analyzed. Genes that were specifically upregulated in HAGC were identified, and their effect on cell migration and invasion was studied. The function of ACTN2 gene were confirmed by GC cell lines, bone-metastatic animal model and patients' tissues. Furthermore, the molecular mechanism of ACTN2 derived-BMM was explored by multiple immunofluorescence staining, western blot, chromatin immunoprecipitation, and luciferase reporter assays. RESULTS: We elucidated the key mechanisms of BMM depending on the transcriptomic difference between HAGC and NAGC. Five genes specifically upregulated in HAGC were assessed their effect on cell migration and invasion. The ACTN2 gene encoding protein α-Actinin-2 was detected enhanced the metastatic capability and induced BMM of GC cells in mouse models. Mechanically, α-Actinin-2 was involved in filopodia formation where it promoted the Actin filament cross-linking by replacing α-Actinin-1 to form α-Actinin-2:α-Actinin-4 complexes in GC cells. Moreover, NF-κB subunit RelA and α-Actinin-2 formed heterotrimers in the nuclei of GC cells. As a direct target of RelA:α-Actinin-2 heterotrimers, the ACTN2 gene was a positive auto-regulatory loop for α-Actinin-2 expression. CONCLUSIONS: We demonstrated a link between filopodia, BMM and ACTN2 activation, where a feedforward activation loop between ACTN2 and RelA is established via actin in response to distant metastasis. Given the novel filopodia formation function and the new mechanism of BMM in GC, we propose ACTN2 as a druggable molecular vulnerability that may provide potential therapeutic benefit against BMM of GC.

Intraductal papillary mucinous neoplasm originating from a jejunal heterotopic pancreas: A case report.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is a rare pancreatic tumor and has the potential to become malignant. Surgery is the most effective treatment at present, but there is no consensus on the site of resection. Heterotopic pancreas occurs in the gastrointestinal tract, especially the stomach and duodenum but is asymptomatic and rare. We report a case of ectopic pancreas with IPMN located in the jejunum. CASE SUMMARY: A 56-year-old male patient suffered from severe pain, nausea and vomiting due to a traffic accident and sought emergency treatment at our hospital. Contrast-enhanced computed tomography of the whole abdomen suggested splenic congestion, which was considered to be splenic rupture. Emergency laparotomy was performed, and the ruptured spleen was removed during the operation. Unexpectedly, a cauliflower-like mass of about 2.5 cm × 2.5 cm in size was incidentally found about 80 cm from the ligament of Treitz during the operation. A partial small bowel resection was performed, and postoperative pathology confirmed the small bowel mass as heterotopic pancreas with low-grade IPMN. CONCLUSION: Ectopic pancreas occurs in the jejunum and is pathologically confirmed as IPMN after surgical resection.

Covalent Bond Interfacial Recognition of Polysaccharides/Silica Reinforced High Internal Phase Pickering Emulsions for 3D Printing.

Significant challenges remain in designing sufficient viscoelasticity polysaccharide-based high internal phase Pickering emulsions (HIPPEs) as soft materials for 3D printing. Herein, taking advantage of the interfacial covalent bond interaction between modified alginate (Ugi-OA) dissolved in the aqueous phase and aminated silica nanoparticles (ASNs) dispersed in oil, HIPPEs with printability were obtained. Using multitechniques coupling a conventional rheometer with a quartz crystal microbalance with dissipation monitoring, the correlation between interfacial recognition coassembly on the molecular scale and the stability of whole bulk HIPPEs on the macroscopic scale can be clarified. The results showed that Ugi-OA/ASNs assemblies (NPSs) were strongly retargeted into the oil-water interface due to the specific Schiff base-binding between ASNs and Ugi-OA, further forming thicker and more rigid interfacial films on the microscopic scale compared with that of the Ugi-OA/SNs (bared silica nanoparticles) system. Meanwhile, flexible polysaccharides also formed a 3D network that suppressed the motion of the droplets and particles in the continuous phase, endowing the emulsion with appropriately viscoelasticity to manufacture a sophisticated "snowflake" architecture. In addition, this study opens a novel pathway for the construction of structured all-liquid systems by introducing an interfacial covalent recognition-mediated coassembly strategy, showing promising applications.

Aerobic exercises regulate the epididymal anion homeostasis of high-fat diet-induced obese rats through TRPA1-mediated Cl- and HCO3- secretion†.

Aerobic exercises could improve the sperm motility of obese individuals. However, the underlying mechanism has not been fully elucidated, especially the possible involvement of the epididymis in which sperm acquire their fertilizing capacity. This study aims to investigate the benefit effect of aerobic exercises on the epididymal luminal milieu of obese rats. Sprague-Dawley male rats were fed on a normal or high-fat diet (HFD) for 10 weeks and then subjected to aerobic exercises for 12 weeks. We verified that TRPA1 was located in the epididymal epithelium. Notably, aerobic exercises reversed the downregulated TRPA1 in the epididymis of HFD-induced obese rats, thus improving sperm fertilizing capacity and Cl- concentration in epididymal milieu. Ussing chamber experiments showed that cinnamaldehyd (CIN), agonist of TRPA1, stimulated an increase of the short-circuit current (ISC) in rat cauda epididymal epithelium, which was subsequently abolished by removing the ambient Cl- and HCO3-. In vivo data revealed that aerobic exercises increased the CIN-stimulated Cl- secretion rate of epididymal epithelium in obese rats. Pharmacological experiments revealed that blocking cystic fibrosis transmembrane regulator (CFTR) and Ca2+-activated Cl- channel (CaCC) suppressed the CIN-stimulated anion secretion. Moreover, CIN application in rat cauda epididymal epithelial cells elevated intracellular Ca2+ level, and thus activate CACC. Interfering with the PGHS2-PGE2-EP2/EP4-cAMP pathway suppressed CFTR-mediated anion secretion. This study demonstrates that TRPA1 activation can stimulate anion secretion via CFTR and CaCC, which potentially forming an appropriate microenvironment essential for sperm maturation, and aerobic exercises can reverse the downregulation of TRPA1 in the epididymal epithelium of obese rats.

Prevalence and Antifungal Susceptibility of Sporothrix species in Guangzhou, Southern China.

INTRODUCTION: Sporotrichosis is a subcutaneous and chronic infection caused by traumatic inoculation of pathogenic sporothrix species, usually infecting the skins and subcutaneous tissues of humans and animals. However, the lack of epidemiological data required further molecular identification to describe the distribution of this fungus in our region. In this study, forty-eight clinical sporothrix isolated from Sun Yat-Sen Memorial Hospital were classified, and the susceptibility of each strain to seven antifungal agents was determined. METHODS: Forty strains of S. globosa and eight strains of S. shenkshii were identified via colony morphology and PCR sequencing of calmodulin gene. RESULTS: Antifungal susceptibility tests of the mycelial phase in vitro showed terbinafine (TRB) and luliconazole (LULI) were the most effective, followed by itraconazole (ITZ) and amphotericin B (AMB). By contrast, voriconazole (VCZ), 5-flucytosine (5FC) and fluconazole (FCZ) have low efficacy with high MIC. CONCLUSION: Our results showed a predominantly S. globosa infection trend in southern China. Simultaneously, sporothrix is sensitive to TRB, LULI, ITZ and AMB whereas resistant to FCZ. This study firstly reports antifungal sensitivity test in vitro and epidemiological correlation analysis of sporothrix in southern China, and also the first time to find that sporothrix is sensitive to LULI.

Light-adjusted supramolecular host-guest interfacial recognition for reconfiguring soft colloidal aggregates.

The soft interfacial template-assisted confined self-assembly of block copolymers (BCPs) guiding colloidal aggregates has been extensively investigated by interfacial instability. Whether the macromolecular polymer architectonics possessed stimulus-responsive self-regulated structural controllability more readily implement the morphological diversity of colloidal aggregates. Herein, we in-situ constructed the alginate-modified ß-cyclodextrin/azobenzene-functionalized alkyl chains (Alg-ß-CD/AzoC12) system by supramolecular host-guest interfacial recognition-engineered strategy, in which possessed photo-stimulated responsive structural reconfigurability by modulating assembly/disassembly behaviors between CD and Azo at oil/water interface. The host-guest droplet interfaces acted as soft templates managing interfacial instability by synergistically integrating supra-amphiphilic host-guest polymers with cosurfactants, further constructing various soft supracolloidal aggregates, including soft nanoaggregates, microspheres with tunable degrees of surface roughness. Additionally, the stimuli-altering structural reconfigurability of supramolecular host-guest polymers was regulated by ultraviolet/visible irradiation, endowing soft aggregates with structural diversity. It's highly anticipated that the supramolecular host-guest interfacial recognition self-assembly establishes great bridge between supramolecular host-guest chemistry and colloid interface science.

Shen Qi Wan attenuates renal interstitial fibrosis through upregulating AQP1.

Renal interstitial fibrosis (RIF) is the crucial pathway in chronic kidney disease (CKD) leading to the end-stage renal failure. However, the underlying mechanism of Shen Qi Wan (SQW) on RIF is not fully understood. In the current study, we investigated the role of Aquaporin 1 (AQP1) in SQW on tubular epithelial-to-mesenchymal transition (EMT). A RIF mouse model induced by adenine and a TGF-ß1-stimulated HK-2 cell model were etablished to explore the involvement of AQP 1 in the protective effect of SQW on EMT in vitro and in vivo. Subsequently, the molecular mechanism of SQW on EMT was explored in HK-2 cells with AQP1 knockdown. The results indicated that SQW alleviated kidney injury and renal collagen deposition in the kidneys of mice induced by adenine, increased the protein expression of E-cadherin and AQP1 expression, and decreased the expression of vimentin and α-smooth muscle actin (α-SMA). Similarly, treatmement with SQW-containing serum significantly halted EMT process in TGF-ß1 stimulated HK-2 cells. The expression of snail and slug was significantly upregulated in HK-2 cells after knockdown of AQP1. AQP1 knockdown also increased the mRNA expression of vimentin and α-SMA, and decreased the expression of E-cadherin. The protein expression of vimentin increased, while the expression of E-cadherin and CK-18 significantly decreased after AQP1 knockdown in HK-2 cells. These results revealed that AQP1 knockdown promoted EMT. Furthermore, AQP1 knockdown abolished the protective effect of SQW-containing serum on EMT in HK-2 cells. In sum, SQW attentuates EMT process in RIF through upregulation of the expression of AQP1.

Split-Level Evolutionary Neural Architecture Search With Elite Weight Inheritance.

Neural architecture search (NAS) has recently gained extensive interest in the deep learning community because of its great potential in automating the construction process of deep models. Among a variety of NAS approaches, evolutionary computation (EC) plays a pivotal role with its merit of gradient-free search ability. However, a massive number of the current EC-based NAS approaches evolve neural architectures in an absolutely discrete manner, which makes it tough to flexibly handle the number of filters for each layer, since they often reduce it to a limit set rather than searching for all possible values. Moreover, EC-based NAS methods are often criticized for their inefficiency in performance evaluation, which usually requires laborious full training for hundreds of candidate architectures generated. To address the inflexible search issue on the number of filters, this work proposes a split-level particle swarm optimization (PSO) approach. Each dimension of the particle is subdivided into an integer part and a fractional part, encoding the configurations of the corresponding layer, and the number of filters within a large range, respectively. In addition, the evaluation time is greatly saved by a novel elite weight inheritance method based on an online updating weight pool, and a customized fitness function considering multiple objectives is developed to well control the complexity of the searched candidate architectures. The proposed method, termed split-level evolutionary NAS (SLE-NAS), is computationally efficient, and outperforms many state-of-the-art peer competitors at much lower complexity across three popular image classification benchmark datasets.