Search

Infection by bacteria leads to tissue damage and inflammation, which need to be tightly controlled by host mechanisms to avoid deleterious consequences. It is previously reported that TMEM16F, a calcium‐activated lipid scramblase expressed in various immune cell types including T cells and neutrophils, is critical for the control of infection by bacterium Listeria monocytogenes (Lm) in vivo. This function correlated with the capacity of TMEM16F to repair the plasma membrane (PM) damage induced in T cells in vitro, by the Lm toxin listeriolysin O (LLO). However, whether the protective effect of TMEM16F on Lm infection in vivo is mediated by an impact in T cells, or in other cell types, is not determined. Herein, the immune cell types and mechanisms implicated in the protective effect of TMEM16F against Lm in vivo are elucidated. Cellular protective effects of TMEM16F correlated with its capacity of lipid scrambling and augment PM fluidity. Using cell type‐specific TMEM16F‐deficient mice, the indication is obtained that TMEM16F expressed in liver Kupffer cells (KCs), but not in T cells or B cells, is key for protection against Listeria in vivo. In the absence of TMEM16F, Listeria induced PM rupture and fragmentation of KCs in vivo. KC death associated with greater liver damage, inflammatory changes, and dysregulated liver metabolism. Overall, the results uncovered that TMEM16F expressed in Kupffer cells is crucial to protect the host against Listeria infection. This influence is associated with the capacity of Kupffer cell‐expressed TMEM16F to prevent excessive inflammation and abnormal liver metabolism. [ABSTRACT FROM AUTHOR]

This study presents the design, synthesis, and comprehensive characterization of a novel series of D‐π‐A type malononitrile‐derived chromophores, BTC‐1–BTC‐4. Combining various spectroscopic techniques, nonlinear Z‐scan measurements, and quantum chemical calculations, we revealed the intricate relationship between nonlinear optical properties and the interplay of molecular structure, intramolecular charge transfer (ICT), and dipole moments (μ). Our experimental and computational findings corroborate that the polarization degree in the ground state, the charge separation in the excited state and twisted intramolecular charge transfer (TICT) collectively dictate the nonlinear optical properties of the compounds. Notably, BTC‐1 exhibits an exceptional nonlinear absorption coefficient β value (2×10−8 m W−1), attributed to its optimized charge transfer efficiency and pronounced degree of charge separation. Our findings provide actionable insights for the rational design of high‐performance organic Nonlinear optics (NLO) materials with potential applications in advanced photonic devices. [ABSTRACT FROM AUTHOR]

Hydrogenation of furfural to furfuryl alcohol under H2 and N2 atmosphere was studied over zirconium phosphonate (ZrPO)‐supported PdCu (PdCu/ZrPO) catalysts. The direct hydrogenation and transfer hydrogenation activities of PdCu metal active sites and the transfer hydrogenation activity of Zr4+−O2− Lewis acid‐basic sites were investigated, respectively. The size and the distribution of Cu particles could be adjusted by altering the P/Zr molar ratio. Bimetallic PdCu could enhance the acidity of the PdCu/ZrPO catalysts, and improve the ratio of Lewis/Brønsted acid, which led to an increase in the transfer hydrogenation activity of Lewis acid‐basic pairs. The electronic effect between Pd and Cu promoted furfural to absorb onto electron‐deficient Cu through η1(O)‐aldehyde configuration, which contributed to the direct hydrogenation and the transfer hydrogenation at metal active sites. Especially, the adsorption and dissociation of H2 in electron‐rich Pd were promoted, which significantly improved the direct hydrogenation activity. [ABSTRACT FROM AUTHOR]

Background: To date, carbohydrate antigen 19‐9 (CA19‐9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients. Methods: A total of 1121 patients from the Liver Cancer Clin‐Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular‐cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness. Results: ROC curves obtained by combining CA50, CA19‐9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856–0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841–0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853–0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818–0.927, 94.2%, and 64.6%) in the validation cohort. Conclusion: The model combining CA50, CA19‐9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC. [ABSTRACT FROM AUTHOR]

Background: The surge in omicron variants has caused nationwide breakthrough infections in mainland China since the December 2022. In this study, we report the neutralization profiles of serum samples from the patients with breast cancer and the patients with liver cancer who had contracted subvariant breakthrough infections. Methods: In this real‐world study, we enrolled 143 COVID‐19‐vaccinated (81 and 62 patients with breast and liver cancers) and 105 unvaccinated patients with cancer (58 and 47 patients with breast and liver cancers) after omicron infection. Anti‐spike receptor binding domain (RBD) IgGs and 50% pseudovirus neutralization titer (pVNT50) for the preceding (wild type), circulating omicron (BA.4‐BA.5, and BF.7), and new subvariants (XBB.1.5) were comprehensively analyzed. Results: Patients with liver cancer receiving booster doses had higher levels of anti‐spike RBD IgG against circulating omicron (BA.4‐BA.5, and BF.7) and a novel subvariant (XBB.1.5) compared to patients with breast cancer after breakthrough infection. Additionally, all vaccinated patients produced higher neutralizing antibody titers against circulating omicron (BA.4‐BA.5, and BF.7) compared to unvaccinated patients. However, the unvaccinated patients produced higher neutralizing antibody against XBB.1.5 than vaccinated patients after Omicron infection, with this trend being more pronounced in breast cancer than in liver cancer patients. Moreover, we found that there was no correlation between anti‐spike RBD IgG against wildtype virus and the neutralizing antibody titer, but a positive correlation between anti‐spike RBD IgG and the neutralizing antibody against XBB.1.5 was found in unvaccinated patients. Conclusion: Our study found that there may be differences in vaccine response and protective effect against COVID‐19 infection in patients with liver and breast cancer. Therefore, we recommend that COVID‐19 vaccine strategies should be optimized based on vaccine components and immunology profiles of different patients with cancer. [ABSTRACT FROM AUTHOR]

Summary: Psyllium husk has attracted increasing interest in food applications due to its well‐known health benefits. Size reduction is an important mechanical operation used to tailor the functional properties of materials. In this study, the physicochemical properties and colloidal stability of the PHPs with different sizes were characterised by particle size distribution, zeta potential, Fourier transform infrared (FT‐IR) and X‐ray photoelectron spectroscopy (XPS). Furthermore, the size effects of psyllium husk on surimi gel properties were investigated in terms of the gel strength, water‐holding capacity (WHC) and water distribution. The results found that milling changed the monosaccharide composition and increased the diffraction intensity of psyllium husk powder (PHP) without disrupting the β‐glycosidic linkages. Furthermore, the XPS results suggested that smaller samples showed more exposed surface functional groups. The PHP3 group with average size of d (0.5) = 259.50 μm exhibited the highest absolute zeta potential. The viscosity and zeta potential of PHP correlated positively and negatively with the gel strength of surimi, respectively. Moreover, the micronized PHP also contributed to the increase in immobilised water content and uniform water distribution in surimi gels. The high viscosity and colloidal stability of psyllium husk (PHP3 group) contributed to the improved mechanical properties of surimi gels. This work provides a valuable reference for the potential use of psyllium husk in quality improvement of surimi products through size control. [ABSTRACT FROM AUTHOR]

Non‐thermal plasma (NTP) catalysis, mirroring the trend towards non‐conventional electron‐mediated molecular activation, unfolds novel routes for chemical reactions. Operating at ambient pressure, lower temperatures, and energized by electricity that can powered by renewable sources, NTP offers a cost‐effective and efficient means of sustainable fuel production. This approach has the potential to revolutionize the oil and gas industry, meeting current energy demands while circumventing the challenges posed by conventional thermal catalysis processes, thereby enhancing environmental sustainability and energy security. Through an exploration of the synergistic effects between plasma, catalysis, and hydrocarbon molecules, this concept paper emphasizes the significant advancements made in in‐liquid plasma catalysis strategies for fuel production from heavy oil upgrading. We also provide insights into the heterogeneous catalyst design and the role of plasma gas as an additional catalyst for achieving efficient and sustainable energy solutions. The prospects of in‐liquid plasma catalysis, emphasizing its transformative role in shaping the energy future, are also discussed. [ABSTRACT FROM AUTHOR]

Background: Flortaucipir F18 was the first FDA approved PET tracer to detect tau pathology. Previous studies show that Flortaucipir is more sensitive to Alzheimer's disease (AD) tau than four‐repeat tauopathies. Furthermore, the neurobiological basis of low Flortaucipir signal remain unclear, especially in basal ganglia. In this study, we aimed to identify the contributions of p‐tau (Ser 202), iron and MAOB to Flortaucipir signal in different tauopathies by performing voxel‐to‐voxel correlations between histological inclusion density maps and ante‐mortem flortaucipir PET uptake. Method: Coronal slides of ∼1cm thickness from four tauopathy cases (AD, progressive supranuclear palsy, corticobasal degeneration, and FTLD due to MAPT mutation P305S) and one FTLD‐TDP type‐A case were processed following a computational/histopathology pipeline (Ushizima, Chen, et al. 2021), allowing for whole 3D reconstruction of the histological maps at microscopical level, point‐by‐point aligned to their corresponding MRI T1 images (Figure 1). Serial 120 µm‐thick histological slides underwent immunohistochemistry to p‐tau (Ser 202, CP‐13) and MAOB, and Perl's iron staining. Density of pathological changes per voxel (1.22×1.22×120um³) was measured using convolution neural network algorithm. Flortaucipir images were thresholded at 1.2 SUVR. Spearman's bivariate and multiple linear regressions were used to compare Flortaucipir PET uptake to histological CP13/iron/MAOB counterparts. We examined both areas with high Flortaucipir PET uptake and high histological CP13/iron/MAOB burden. Result: Table 1 show patient features. Figure 2 depicts voxel‐to‐voxel correlations result in scatter plot and bivariate/multiple linear regression analysis. Conclusion: The correlation of CP13 (p‐Tau) to Flortaucipir was higher in AD than other tauopathies. Iron deposits contributed to Flortaucipir uptake in regions both with or without histopathologically confirmed p‐tau, including basal ganglia, whereas MAOB contribution was almost null in gray matter. The time gap between PET and autopsy and lower PET resolution compared to histology may explain the moderate regression coefficients, but other unexplored contributors cannot be discarded. Voxel‐to‐voxel histology to neuroimaging correlations allow for investigating multiple components of the neurological basis of PET. We are finalizing the regression analysis based on areas of high histological burden. [ABSTRACT FROM AUTHOR]

Background: Blinatumomab improved survival outcomes in B‐cell acute lymphoblastic leukemia (B‐ALL) patients with measurable residual disease (MRD) <10−4. However, data on blinatumomab clearing MRD with high sensitivity of 10−6 remain scarce. This study evaluates the effectiveness of blinatumomab in eradicating extremely low level (up to <10−6) of MRD, as detected by next‐generation sequencing (NGS), in children with B‐ALL. Methods: Patients (n = 19) whose MRD was undetectable by multiparameter flow cytometry (MFC) (sensitivity of 10−4) but detectable by NGS after chemotherapy and followed by blinatumomab consolidation were included retrospectively. Results: After one course of blinatumomab, 13/19 patients (68%) successfully achieved NGS‐MRD clearance (undetectable). With a median follow‐up of 13.3 months, three of patients who were NGS‐MRD positive relapsed within 1.8 months, while another three remained complete remission. Conclusions: Our study was the first to demonstrate that blinatumomab could further eradicate MRD after patients achieve MFC‐MRD undetectable in B‐ALL patients. [ABSTRACT FROM AUTHOR]

Background: Individuals with neuropathological criteria for Alzheimer's disease (AD) may manifest with atypical clinical syndromes. Past work showed that the neurobiological basis for these differences is related to specific neuronal vulnerabilities for tau pathology. For instance, amnestic cases have a higher burden of neurofibrillary changes in CA1. In contrast, logopenic variant primary progressive aphasia (lvPPA) cases have a higher tau burden in the superior temporal gyrus (STG). Single‐cell technology enables investigations on the molecular basis of differential neuronal vulnerability in AD. Therefore, we investigated factors underlying selective vulnerability using brain samples from individuals with pure AD with different clinical manifestations. Method: snRNA Sequencing using the Chromium Single Cell 3′ (10X Genomics, USA) on nuclei cells extracted from the CA1 sector and posterior STG of postmortem brain tissue of 24 individuals either meeting pathological criteria for AD (A3B3C3; 12 amnestic and eight lvPPA) and healthy controls (A≤1B≤1C≤1; n = 4) (Table 1, Fig. 1A/B). Bioinformatics analyses were conducted using Cell Ranger and R software. Comparisons between cell subpopulations were conducted with Wald statistical test, and p‐values <.05 were considered significant. Result: After quality control, we recovered 98,180 nuclei with a mean of 2,130 genes per nuclei. Upon cross‐sample alignment and t‐stochastic neighborhood embedding clustering (Fig. 1C), we found 21 excitatory neuronal subpopulations (Exc‐sub) in CA1 and 26 in STG, and 22 and 27 inhibitory neuronal subpopulations (Inh‐sub) in CA1 and STG, respectively; 16 astrocytes subpopulations in both areas and 20 microglia subpopulations in CA1 and 17 in STG (Fig. 2). One STG Exc‐sub, expressing CUX2 and LAMP5 genes showed vulnerability in lvPPA patients. Also, one STG Inh‐sub, expressing the ADARB2 gene, showed vulnerability for all AD patients. Furthermore, two astrocytes subpopulations (one in both areas and one in STG) and three STG microglia subpopulations showed proportional composition changes comparing AD patients and HC. Conclusion: Our preliminary study identified a vulnerable population of excitatory neurons related to lvPPA. We are conducting validation studies using quantitative pathology to confirm these results. Furthermore, analysis of a higher number of cases is ongoing and will continue to inform on factors associated with neuronal vulnerability. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's Disease (AD) patients commonly experience sleep/wake (S/W) disturbances, such as sleep fragmentation and excessive daytime sleepiness. The S/W cycle is controlled by a complex system regulated by a master regulator, the suprachiasmatic nucleus (SCN) that controls wake‐ and sleep‐promoting nuclei. Despite its importance in orchestrating sleep architecture, little is known about the molecular changes that occur in the SCN during the progression of AD and how these changes contribute to S/W disturbances. Method: We used postmortem brain tissue of 10 controls without AD pathology and 32 subjects with progressive AD stages. Our approach included quantitative neuropathological assessments of AVP and VIP‐expressing neurons in SCN and its adjacent hypothalamic region, the supraoptic nucleus (SON). We also used an in‐situ cell‐specific spatial proteomics platform [GeoMx Digital Spatial Profiling (DSP)] to probe levels of different pathological tau species and proteins commonly dysregulated in AD. Result: Preliminary findings reveal a significant decrease in SCN volume (∼75%) (Fig.1) and a loss of ∼58% AVP neurons and ∼41% VIP neurons in Braak stage (Braak) VI compared to Braak 0. The DSP results indicate that both neurons in the SCN have twice the burden of p‐tau levels as the SON (Fig.2‐right), and neurofibrillary tanglesAdditionally, SCN shows an increase in proteins associated with glia and immune responses (Fig.2‐left). Furthermore, an increase in microglial proteins is observed in the SCN in Braak I (Fig.3‐left). In contrast, the SON displays a milder pattern of protein dysregulation in Braak I (Fig.3‐right), consistent with its lower tau expression observed in histology and DSP. Conclusion: SCN is vulnerable to AD pathology even in Braak I, which is characterized by volume loss, increased immune response protein dysregulation, and later neuronal loss, as well as p‐tau pathology. This pattern supports the idea that the SCN plays a role in S/W disturbances observed from early AD stages. Interestingly, its neighboring nucleus, SON, which also has AVP neurons, remained spared, providing opportunities for studies investigating factors related to selective vulnerability. Ongoing studies are addressing changes in the SCN and SON in intermediate AD stages. [ABSTRACT FROM AUTHOR]

The −NH2 in UiO‐66‐NH2 was functionally modified with 2‐pyridinecarboxaldehyde to form Schiff base UiO‐66‐Pyr, and hollow nitrogen‐doped porous carbon‐ZrO2 supported Ru (Ru/NC‐ZrO2) was prepared from Ru3+‐coordinated UiO‐66‐Pyr‐Ru. Then the furfural hydrogenation performance of the product was investigated. Compared with single‐tooth‐coordinated UiO‐66‐NH2, the 2‐tooth‐coordinated UiO‐66‐Pyr can improve the stability of Ru3+ coordination and thereby increase the Ru loading and dispersity in the Ru/NC‐ZrO2, showing high furfural hydrogenation activity. The direct hydrogenation with hydrogen as the hydrogen source and the transfer hydrogenation with isopropanol as the hydrogen donor was determined by the furfural hydrogenation of Ru/NC‐ZrO2 under hydrogen or nitrogen. [ABSTRACT FROM AUTHOR]

Ammonia is crucial for human life as an important ingredient for fertilizer, industrial and household chemicals, and is considered as a future fuel alternative and hydrogen storage molecule. There remain no viable alternatives to the energy‐and capital‐intensive Haber–Bosch (H−B) process. Efforts in the development of novel catalytic processes operated at milder conditions (low temperatures and ambient pressure), prominently electrochemistry and non‐thermal plasma (NTP), and utilization of lower‐cost H sources for ammonia formation than the ultrapure H2 have been witnessed in the last few years. Yet, limited progress from these routes has been made to date given unresolved low ammonia yield and technical challenges. Several rare works attempted to activate methane (CH4) and nitrogen (N2) by non‐thermal plasma to produce ammonia and valued‐added hydrocarbons have proven to be a promising research direction, rivalling the reaction between N2 and ultrapure H2 or water. The direct conversion of CH4 and N2 to ammonia is still at the beginning level, and it remains unclear that what extent these technologies must be improved to develop a commercial process. Toward this goal, this Perspective critiques current steps and miss‐steps of sustainable plasma catalytic ammonia production from CH4 and N2 in terms of technology, plasma‐catalyst synergy, mechanistic insights, and experimental protocols. We discuss mechanistic understandings of catalyst‐promoted ammonia production and translate such discussions as well as key metrics achieved in the field into recommendations of feasible processes for ammonia and value‐added hydrocarbons formation from CH4 and N2. [ABSTRACT FROM AUTHOR]

The development of a non‐noble metal cathode ORR catalyst with low cost, high activity and high stability has become an inevitable trend in MFC. The purpose of this study is to develop an efficient and stable Cu, N‐codoped porous carbons catalysts with multi‐pore structure for MFC. Herein, Cu, N‐codoped porous carbons materials (Cu−NC−T) with high N content and multi‐pore structure were successfully developed by co‐pyrolysis with MOF‐199 and melamine. By contrast, Cu‐doped porous carbon (Cu−C−T) without melamine was synthesized using MOF‐199 as template. The results showed that Cu−NC−T possessed a rough octahedral crystal with a unique multi‐mesopore structure with pore centers of 3.4 nm and 11.2 nm, respectively. Owing to high N content, abundantly exposed Cu−Nx active sites and the multi‐pore structure, Cu−NC−800 had a pronounced electrochemical ORR activity in neutral solution (onset potential and limiting current density were 0.161 V and −6.256 mA ⋅ cm−2), which were slightly lower than 20 wt % Pt/C (0.189 V and −6.479 mA ⋅ cm−2). Moreover, the MFC with Cu−NC−800 showed a power density of 662.8±3.6 mW ⋅ m−2, which was higher than that of Cu−C−800 (425.7±3.9 mW ⋅ m−2) and was slightly lower than that 20 wt % Pt/C (815.0±6.2 mW ⋅ m−2). The output voltage of MFC with Cu−NC−T had no obvious decreasing trend in 30 days, demonstrating that the Cu−NC−T had great stability. [ABSTRACT FROM AUTHOR]

Apis laboriosa is the largest honeybee that lives mainly on cliff faces, with strong migratory ability. In this study, we firstly sequenced and assembled two complete mitochondrial genomes of A. laboriosa isolated from two distant locations in China (Chongqing and Shangri‐La regions). Combined with the published mitochondrial genome of A. laboriosa from Nepal, comparative genomic analyses were conducted to gain insight into the genetic diversity of giant honeybees from different geographical distributions. The mitochondrial genomes of A. laboriosa from Chongqing and Shangri‐La regions were 15,579 and 15,683 bp in length, respectively, both larger than that from Nepal with the length of 15,510 bp. Three mitochondrial genomes all harbor 37 common genes and present the same AT bias and the frequency of codon usage. However, the fragments including COX1, SSUrRNA, LSUrRNA, and the AT‐rich region of the mitochondrial genome from Shangri‐La region demonstrate distinctive insertions and deletions compared to those from Chongqing and Nepal regions. Phylogenetic trees of mitochondrial genomes show that A. laboriosa from Chongqing is most closely related to that from Nepal, rather than to Shangri‐La. Genetic distance between Shangri‐La and Chongqing or Nepal was even larger than that between the various subspecies of Apis mellifera. Overall, these results unmark that A. laboriosa in different geographical distributions can exhibit high genetic diversity at the mitochondrial genomic level, and therein, A. laboriosa from Shangri‐La may be the subspecies. All these studies will contribute to our understanding of the geographical distribution and genetic differentiation of black giant honeybee in Asian region. [ABSTRACT FROM AUTHOR]

Mixed human umbilical cord‐derived mesenchymal stem cells (UC‐MSCs) are widely applied in clinical trials to treat various diseases due to their multipotent differentiation potential and immune regulatory activities. However, the lack of a clear understanding of their heterogeneity hampers their application to precisely treat diseases. Moreover, few studies have experimentally authenticated the functions of so‐called UC‐MSC subpopulations classified from scRNA‐seq samples. Here, this work draws a large‐scale single‐cell transcriptomic atlas and identified three clusters (C1, C2, and C3), representing the primed, intermediate, and stem statuses individually. The C1 and C3 clusters feature higher expression of cytokines and stemness markers, respectively. Surprisingly, further experimental assays reveal that the BAMBIhighMFGE8high C1 subgroup has a unique phenotype, distinct transcriptomic profile, and limited adipogenic differentiation potential but compromised immunosuppressive activity in vitro and in vivo in lupus mice. Thus, this work is helpful to clarify the nature of human UC‐MSCs and to choose optimal MSC types to treat specific diseases in the future. [ABSTRACT FROM AUTHOR]

Hybrid zones have been widely highlighted for their interest in understanding evolutionary processes. It is generally accepted that hybrid zones can be maintained in a balance between dispersal and selection. However, the selective forces can either be endogenous (i.e., genetic incompatibilities between parental taxa) or exogenous (i.e., parental taxa are adapted to different environments). In this study, we evaluated these alternatives and determined the maintenance of a narrow hybrid zone between parapatric distributed Oxytropis diversifolia and O. leptophylla in Nei Mongol, China. For 507 individuals sampled from two populations in the hybrid zone, 12 O. diversifolia populations and five O. leptophylla populations, we measured leaf‐morphological characteristics, quantified genetic structure using 11 nuclear microsatellite loci and five chloroplast DNA intergenic regions, collected micro‐ and macrohabitat data, and conducted geographical cline analysis. We found that the two species differed in leaf morphology, and putative hybrids showed either intermediacy or a bias to O. diversifolia. Parental taxa formed two genetically distinct clusters, while populations in the hybrid zone consisted of both parental forms and various admixed individuals, exhibiting a bimodal pattern. The hybrid zone was coupled to ecological transitions of both microhabitat (i.e., the slope) and macroclimatic conditions. However, the genetic clines were significantly narrower than the environmental cline. Our results indicate that endogenous selection can be primarily responsible for maintaining the hybrid zone, while local adaptation accounts for the position of the zone. We further suggest the probable outcome of hybridization could be introgression. [ABSTRACT FROM AUTHOR]

Aim: Tau truncation (tr‐tau) by active caspase‐6 (aCasp‐6) generates tau fragments that may be toxic. Yet the relationship between aCasp‐6, different forms of tr‐tau and hyperphosphorylated tau (p‐tau) accumulation in human brains with Alzheimer's disease (AD) and other tauopathies remains unclear. Methods: We generated two neoepitope monoclonal antibodies against tr‐tau sites (D402 and D13) targeted by aCasp‐6. Then, we used five‐plex immunofluorescence to quantify the neuronal and astroglial burden of aCasp‐6, tr‐tau, p‐tau and their co‐occurrence in healthy controls, AD and primary tauopathies. Results: Casp‐6 activation was strongest in AD and Pick's disease (PiD) but almost absent in 4‐repeat (4R) tauopathies. In neurons, the tr‐tau burden was much more abundant in AD and PiD than in 4R tauopathies and disproportionally higher when normalising by p‐tau pathology. Tr‐tau astrogliopathy was detected in low numbers in 4R tauopathies. Unexpectedly, about half of tr‐tau positive neurons in AD and PiD lacked p‐tau aggregates, a finding we confirmed using several p‐tau antibodies. Conclusions: Early modulation of aCasp‐6 to reduce tr‐tau pathology is a promising therapeutic strategy for AD and PiD but is unlikely to benefit 4R tauopathies. The large percentage of tr‐tau‐positive neurons lacking p‐tau suggests that many vulnerable neurons to tau pathology go undetected when using conventional p‐tau antibodies. Therapeutic strategies against tr‐tau pathology could be necessary to modulate the extent of tau abnormalities in AD. The disproportionally higher burden of tr‐tau in AD and PiD supports the development of biofluid biomarkers against tr‐tau to detect AD and PiD and differentiate them from 4R tauopathies at a patient level. [ABSTRACT FROM AUTHOR]

Herein, a one‐dimensional hollow nanofiber catalyst composed of tightly packed multiphase metal oxides of Mn2O3 and Cu1.4Mn1.6O4 was constructed by electrospinning and tailored thermal treatment procedure. The characterization results comprehensively confirmed the special morphology and composition of various comparative catalysts. This strategy endowed the catalyst with abundant interfacial characteristics of components Mn2O3 and Cu1.4Mn1.6O4 nanocrystal. Impressively, the tuning thermal treatment resulted in tailored CuI sites and surface oxygen species of the catalyst, thus affording optimized oxygen vacancies for reinforced oxygen adsorption, while the concomitant enhanced lattice oxygen activity in the constructed composite catalyst ensured the higher catalytic oxidation ability. More importantly, the regulated proportion of oxygen vacancy and lattice oxygen in the composite catalyst was obtained in the best catalyst, beneficial to accelerate the reaction cycle. Compared to other counterparts obtained by different temperatures, the CMO‐500 sample exhibited superior selective aerobic 5‐hydroxymethylfurfural (HMF) oxidation to 2,5‐furandicarboxylic acid (FDCA, 96 % yield) in alkali‐bearing aqueous solution using O2 at 120 °C, which resulted from the above‐mentioned composition optimization and interfacial engineering reinforced surface oxygen consumption and regeneration cycle. The reaction mechanism was further proposed to uncover the lattice oxygen and oxygen vacancy participating HMF conversion process. [ABSTRACT FROM AUTHOR]

As a promising building block of the emerging neuromorphic computing hardware, memristive structures with multi‐functionalities are highly desired to implement diversified computing applications in a single device. However, the demonstration of such multi‐functional structures remains limited. In this work, an Ag/GeS/Pt‐based bifunctional memory structure with both long‐term and short‐term memristive behaviors is reported, enabling multiple neuromorphic computing applications in a single device. It is found that the unexpected short‐term switching in Ag/GeS/Pt can not only be used to simulate learning/relearning and forgetting behavior but can also be implemented for reservoir computing. While for long‐term switching memristive behavior, its application is demonstrated as the traditional memory. The work reveals a novel coexistence of the two types of resistive switching, shedding light on various neuromorphic computing applications such as reservoir computing and traditional memory realized in a single memristive device. [ABSTRACT FROM AUTHOR]

Mutations of PSEN1 have been reported in dilated cardiomyopathy pedigrees. Understanding the effects and mechanisms of PSEN1 in cardiomyocytes might have important implications for treatment of heart diseases. Here, we showed that PSEN1 was downregulated in ischemia‐induced failing hearts. Functionally, cardiovascular specific PSEN1 deletion led to spontaneous death of the mice due to cardiomyopathy. At the age of 11 months, the ratio of the heart weight/body weight was slightly lower in the Sm22a‐PSEN1‐KO mice compared with that of the WT mice. Echocardiography showed that the percentage of ejection fraction and fractional shortening was significantly reduced in the Sm22a‐PSEN1‐KO group compared with the percent of these measures in the WT group, indicating that PSEN1‐KO resulted in heart failure. The abnormally regulated genes resulted from PSEN1‐KO were detected to be enriched in muscle development and dilated cardiomyopathy. Among them, several genes encode Ca2+ ion channels, promoting us to investigate the effects of PSEN1 KO on regulation of Ca2+ in isolated adult cardiomyocytes. Consistently, in isolated adult cardiomyocytes, PSEN1‐KO increased the concentration of cytosolic Ca2+ and reduced Ca2+ concentration inside the sarcoplasmic reticulum (SR) lumen at the resting stage. Additionally, SR Ca2+ was decreased in the failing hearts of WT mice, but with the lowest levels observed in the failing hearts of PSEN1 knockout mice. These results indicate that the process of Ca2+ release from SR into cytoplasm was affected by PSEN1 KO. Therefore, the abnormalities in Ca2+ homeostasis resulted from downregulation of PSEN1 in failing hearts might contribute to aging‐related cardiomyopathy, which might had important implications for the treatment of aging‐related heart diseases. [ABSTRACT FROM AUTHOR]

Background: Neuroimaging of brainstem structures has gained importance in ADRD as these regions degenerate early in AD. In recent years there has been an explosion of novel neuroimaging sequences to image the brainstem. However, most of these methods lack validation against the ground truth, i.e tissue visualization, making these methods less attractive for clinical use. Among the new proposed methods, high‐definition connectome promises to revolutionize BS imaging as it overcomes several limitations of standard structural MRI, including a high level of imaging deformation. In this project we have developed a pipeline to validate BS connectome sequences using a voxel to voxel comparison between 3D histological volumes and connectome signal. To this date we applied this pipeline to 6 human brains. Method: We used 6 AD cases collected by the Neuroradiology Lab at the University of Sao Paulo. Patients underwent postmortem MRI prior to autopsy.We used a pipeline developed in‐house that allows for precise alignment of histology‐based cytoarchitectural 3D reconstructions of the brainstem to its T2 weighted 7T‐MRI counterpart. Upon procurement, the brains were fixed in formalin, embedded in celloidin, and cut in horizontal sections of 300um. Selected BS structures were delineated on these slides stained for Nissl(gallocyanin)(Fig.1). Delineated images underwent manual quality checks, a series of alignment and registration processes to recover original coordinates. The stained sections and corresponding ROI masks were registered to the blockface to correct for any deformation of tissue during the staining process. Freeview commands applied to reconstruct the brainstems and masks. We registered the resulting 3D reconstruction to the matching MRI coordinates(Fig. 2), enabling voxel‐to‐voxel comparisons. Result: 6 cases went through the pipeline with ROIs reconstructed on block reconstructions(Fig. 3). Currently, dice coefficient analysis between MRI signal and the manually outlined ROIs on histology are being finalized. Conclusion: Our pipeline enables voxel‐to‐voxel correlation analysis between histology and MRI scans for validation of brainstem neuroimaging. Current finalization of a total 9 cases is ongoing. Validation of such correlation maps will inform interpretations of connectome results in living patients with the potential to act as an eventual diagnostic tool for ADRD. [ABSTRACT FROM AUTHOR]

Background: Recent evidence suggests that sleep‐wake dysregulation in Alzheimer's disease (AD) is an early event and parallels the tau accumulation in the arousal system spefically noted in the locus coeruleus (LC) as well as other subcortical nuclei as the Pedunculopontine Tegmental Nucleus (PPTg), Laterodorsal Tegmental Nucleus (LDTg), and the Dorsal Raphe (DR). We have previously demonstrated that the pattern of sleep‐wake dysfunction is different among AD clinical variants. This existence of specific sleep‐wake profiles suggest differential degeneration patterns of the arousal system within differing AD presentations. This study continues this investigation at the cellular/molecular level to uncover the selective vulnerability of subcortical structures to AD specific tau accumulation. That remains elusive to‐date. Method: Human postmortem brainstem samples were sourced from the Neurodegenerative Disease Brain Bank (NDBB) at UCSF. 24 subjects were selected based on primary diagnosis, including 6 amnestic AD, 17 non‐amnestic AD (5 EOAD, 3 PCA, 5 lvPPA, 4 CBS) and 1 control. Paraffin blocks containing the areas of interest were cut into 8‐lm‐thick sections that underwent double‐labeled immunohistochemistry (IHC) and brightfield imaging. The images were then overlayed to created mutlidimentaional maps and neurons were classified in 4 subgroups: (1) positive for the neurotransmitter of interest (NEU‐positive), (2) bearing hyperphosphorylated tau neuronal cytoplasmic inclusions (tau‐positive), (3) positive for the neurotransmitter of interest and bearing tau‐positive (NEU‐positive/tau‐positive colocalized neurons), and (4) negative for NEU and tau. Result: In the LC, lvPPA had the highest had the highest percentage of tau postive neurons (40%), followed by amnestic AD (31.1%), PCA (29.3%), EOAD (27.1%), and finally CBS (24.3%). EOAD had the highest percentage of colocalized neurons (34.7%) as well as LOAD (31%) compared to PCA (0.02%), lvPPA (0.18%), CBS (0.09%). Conclusion: Multidimensional quantitative analysis suggests differences in vulnerabliblity of sleep‐wake subcortical nuclei to AD, EOAD, PCA, lvPPA, and CBS. For instance the neuronal loss in EOAD was so extreme in the LC that few neurons remained to develop aggregates whereas in PCA, CBS, and lvPPA the high percentage of tau accumulation presents a neuropathological framework underlying atypical clinical manifestations and possible insight into therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Studies suggest a decrease in LC volume by 8% each Braak stage, starting at Braak 0‐1, while in normal aging the LC volume remains intact. Thus, LC volumetry is an attractive potential biomarker to monitor AD progression from precognitive stages. However, precise LC volumetry neuroimaging is challenging due to the LC's small size and location in the brainstem that's prone to artifacts. To validate the precision/utility of neuroimaging sequences designed for LC volumetry, we developed a pipeline allowing voxel‐to‐voxel histology to neuroimaging comparisons. We tested this pipeline to analyze the neuro‐histological counterpart of an LC volume obtained from manual segmentation from a MRI neuromelanin(NM)sensitive GRE image. Method: Whole brain high resolution(0.7mm)3D‐T1 images and 2D‐2mm thick NM‐sensitive axial GRE images of the brainstem were obtained postmortem in situ before brain removal from a single subject using a 7T MRI(Siemens Magnetom). We combined celloidin‐based histological processing and 3D reconstructions of the histology volume at microscopic resolution which was then aligned to T1. We used structures visible in structural MRI(T1)(brainstem surface, red nucleus, and 4th ventricle) to calculate Dice coefficient to measure registration accuracy. Next, we performed an overlap percentage analysis to investigate how well GRE sequence detected LC borders compared to histology. Result: We ran Dice coefficient analysis for brainstem structures to measure histology to MRI registration accuracy(Table1). The LC GRE to histology masks overlap percentage was 35.29% and 10.77% compared to the MRI and histology mask total voxels(voxel size = 0.34mm3). The overlap percentage obtained for the rostral and middle LC thirds ranged from 9.43% to 75%when compared to total voxels in MRI/histology masks, while the caudal third had zero overlap(Table2,Fig.1). Conclusion: Our pipeline enables voxel‐to‐voxel correlation analysis between histology and high resolution LC MRIs for neuroimaging validation. The caudal third of the LC in our case has shown a clear lack of overlap potentially due to lack of signal specificity in MRI when compared to the gold standard that is histology. Current analysis of another five other cases is ongoing. Validation of LC MRI signal will inform interpretations of signal results in living patients with the potential to act as a diagnostic tool for ADRD. [ABSTRACT FROM AUTHOR]

In this work, a composite photocatalyst consisted of the porous graphitic carbon nitride (pg‐C3N4) nanosheets decorated with in‐situ grown gold (Au) nanoparticles were prepared. By characterizing and analyzing chemical compositions and structures, and optical and electrical properties of this Au/pg‐C3N4 composite, the excellent photocatalytic performance mainly comes from the following aspects: firstly, pg‐C3N4 synthesized from melamine by high‐temperature calcination with the assistance of ascorbic acid has larger specific surface area and narrower band gap width than common g‐C3N4; secondly, localized surface plasmon resonance (LSPR) effect of Au nanoparticles can enhance light absorption of pg‐C3N4 via near‐field enhancement‐induced excitation; thirdly, the heterojunction formed between Au nanoparticles and pg‐C3N4 nanosheets can promote electron transfer. Consequently, Au/pg‐C3N4 presented the obvious improvement of photocatalytic activity on the degradation of rhodamine B and amaranth under simulated solar irradiation that the kinetic rate constant of degradation reaction can be increased by 3.9 and 5.7 times compared with g‐C3N4, respectively. [ABSTRACT FROM AUTHOR]

Introduction: Metagenomic Next‐Generation Sequencing (mNGS) is an emerging technique for microbial identification and diagnosis of infectious diseases. The clinical utility of mNGS, especially its real‐world impact on antimicrobial treatment and patient outcome has not been systematically evaluated. Methods: We prospectively assessed the effectiveness of mNGS in 70 febrile inpatients with suspected infections at Hematology department of the Children's Hospital, National Clinical Research Center for Child Health. 69/70 patients were given empirical antibiotics prior to mNGS. A total of 104 samples (62 plasma, 34 throat swabs, 4 bone marrow, 4 bronchoalveolar lavage) were collected on day 1‐28 (mean 6.9) following symptom onset and underwent mNGS testing. Results: Traditional microbiological tests discovered causal microorganisms in 5/70 (7.14%) patients, which were also detected by mNGS. In addition, mNGS reported possible pathogens when routine tests were negative. Antibiotics were adjusted accordingly in 55/70 (78.6%) patients that led to improvement/relief of symptoms within 3 days. In contrast, mNGS results were considered irrelevant in 15/70 (21.4%) patients by a board of clinicians, based on biochemical, serological, imaging evidence, and experiences. Conclusion: mNGS expanded the capacity of pathogen detection and made a positive impact on clinical management of suspected infections through (a) differential diagnosis which may rule out infectious diseases and (b) adjustment or de‐escalation of empirical antibiotics. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemoradiotherapy (NACRT) and total mesorectal excision (TME) are standard treatments of stage II/III locally advanced rectal cancer (LARC), currently. Here, we evaluated the oncological outcomes in LARC patients treated with NACRT compared to TME alone, and determined whether tumor regression grade (TRG) and pathologic response after NACRT was related to prognosis. Methods: This is a retrospective comparison of 358 LARC patients treated with either TME alone (non‐NACRT group, n = 173) or NACRT plus TME (NACRT group, n = 185) during 2003–2013. Perioperative and oncologic outcomes, like overall survival (OS), disease‐free survival (DFS) and recurrence were compared using 1:1 propensity score matching analysis. Results: A total of 133 patients were matched for the analysis. After a median follow‐up of 45 months (8–97 months), the 5‐year OS (NACRT vs non‐NACRT: 75.42% vs 72.76%; P = 0.594) and 5‐year DFS (NACRT vs non‐NACRT: 74.25% vs 70.13%; P = 0.224) were comparable between NACRT and non‐NACRT, whereas the 5‐year DFS rate was higher in the NACRT group when only stage IIIb/IIIc patients were considered (NACRT vs. non‐NACRT: 74.79% vs. 62.29%; P = 0.056). In the NACRT group of 185 patients, those with pCR/stage I (vs stage II/stage III disease) or TRG3/TRG4 disease (vs TRG0/TRG1/TRG2) had significantly better prognosis. Conclusion: NACRT might provide survival benefit in patients with stage IIIb/IIIc locally advanced rectal cancer. [ABSTRACT FROM AUTHOR]

Here, a novel approach has been proposed to synthesize NaP zeolite adsorbents doped with transition metals (M‐NaP) using the Na2SiO3 and NaAlO2 compounds extracted from fly ash via activation and stage treatment. The preparation process of M‐NaP employed the in‐situ synthesis in combination with organic complexation method. The effects of the addition amounts and valence state of transition metals on the zeolite products were investigated. The crystalline phase, morphology, and particle size of M‐NaP were characterized using X‐ray diffractometry (XRD), Scanning electron microscopy (SEM), and Laser particle size analyzer (PSD). The doping process was investigated using X‐ray photoelectron spectroscopy (XPS) and Materials Studio. The adsorption performance of M‐NaP was tested by the adsorption of Zn2+. The optimal molar ratio of n(Al2O3)/n(M) was identified as 8:1 for Co–NaP, Ni–NaP, and Fe–NaP, compared with 6:1 for Ti–NaP. The influence of transition metals on adsorption was: Co–NaP > Ni–NaP > Ti–NaP > Fe‐NaP. Due to largest surface area of Co–NaP (162.5 m2/g, five times than that of NaP‐RAW), the maximum removal rate of Zn2+ was above 99.50% at 25°C. The existence state of transition metals in M‐NaP primarily included: isomorphous substitution and balance of the skeletal charge, with the latter in majority. The simulation of Materials Studio indicates that Si at T4 was first substituted and then, Si at T3 opposite T4 was replaced when the replacement of Si in different sites occurred. [ABSTRACT FROM AUTHOR]

Ship tracks appear as long winding linear features in satellite images and are produced by aerosols from ship exhausts changing low cloud properties. They are one of the best examples of aerosol‐cloud interaction experiments. However, manually finding ship tracks from satellite data on a large scale is prohibitively costly while a large number of samples are required to improve our understanding. Here we train a deep neural network to automate finding ship tracks. The neural network model generalizes well as it not only finds ship tracks labeled by human experts but also detects those that are occasionally missed by humans. It finds more ship tracks than all previous studies combined and produces a map of ship track distributions off the California coast that matches well with known shipping traffic. Our technique will enable studying aerosol effects on low clouds using ship tracks on a large scale, which will potentially narrow the uncertainty of the aerosol‐cloud interactions. Key Points: We develop a technique to automatically find ship tracks in large data and create opportunity for large‐scale analysisMore ship tracks are found than all previous studies combined and the technology will be useful to study aerosol indirect effectsShip tracks affect significant, more than 10%, number of low clouds at regional level [ABSTRACT FROM AUTHOR]

Calendula officinalis L., commonly known as marigold, is not only cultivated for ornamental purposes but is also used as a traditional medicinal herb. Its flowers have been used to treat various skin diseases, including rashes, burns, cuts and bruises, since ancient times. However, to our knowledge, the impact of C. officinalis L. on melanoma and its mechanism have not been clarified. The aim of this work was to investigate the chemical characterization and antimelanogenic and antimigration activities of the ethyl acetate fraction of C. officinalis flowers (EFC), as well as elucidate the potential mechanism. The obtained results showed that EFC markedly decreased α‐MSH‐induced melanin production and the cell migration ability of melanoma cells in a dose‐dependent manner. Additionally, EFC significantly inhibited the activity and expression of matrix metalloproteinase 2 (MMP‐2) via suppressing the mitogen‐activated protein kinase (MAPK) signaling pathway. Taken together, the present study demonstrated that C. officinalis flowers can be used as a natural source of antimelanogenisis and antimigration regent to treatment or prevent skin diseases. [ABSTRACT FROM AUTHOR]

Background: The proteolytic ubiquitin‐proteasome system (UPS) is a main control mechanism of tau degradation in eukaryotic cells. Although the UPS is an integral regulator for tau turnover in healthy neurons, preliminary data suggests that the pathological tau in Alzheimer's Disease (AD) is polyubiquitinated. This is an intriguing conundrum where the polyubiquitinylation of tau does not result in the degradation of the protein by the UPS. This suggests that the capacity of the UPS is limited or that the UPS is unable to degrade this form of tau. In this study, we aim to validate this potential correlation between the polyubiquitination of tau and AD, which could perhaps provide more clarity on the specific mechanisms of toxicity for AD. Method: We examined postmortem brain tissue (inferior temporal gyrus) of 11 cases across AD neuropathological spectrum (Table 1). All slides underwent multiplex immunofluorescence for four antibodies: NeuN (neurons), FK2 (to detect polyubiquitin), T231 (ptau), and GFAP (astroglia), followed by scanning and quantification on digital slides. We quantified the percentage of neurons positive for tau (T231) and polyubiquitination (FK2) and analyzed the spearman correlation and linear regression model (LRM) corrected by age on death and sex. Result: Cases represent a spectrum of AD stage. As expected, the proportion of neurons with tau inclusions increase along AD progression. We failed to identify neurons positive for FK2 (polyubiquitination) in the absence of tau and neurons. Moreover, we observed a direct correlation between higher Braak Stages and proportion of neurons with polyubiquitin immunoprecipitations (Figure 1, ρ = 0.89, p = 2.33e‐4). Conclusion: Neurons with polyubiquitin immunoprecipitations increase in number along the AD continuum. These neurons tend to accumulate phospho‐tau inclusions suggesting a polyubiquitination of tau in AD. Further studies are needed to identify the mechanisms underlying the lack of tau degradation by the UPS in this situation, which could lead to treatment opportunities for AD. [ABSTRACT FROM AUTHOR]

Background: : The excitatory neurons of the entorhinal cortex are extremely vulnerable to Alzheimer's disease (AD). Recently, we demonstrated that among those neurons, expressing high levels of RORB, are more vulnerable than other neighboring excitatory neuronal subpopulations. Our single nucleus RNA sequencing of 10 EC at progressive stages of AD neurofibrillary pathology also suggested that CDH9+ excitatory neurons from the EC can also be early vulnerable to AD. Here, we used quantitative neuropathological methods in cases across AD progression to interrogate whether CDH9+ neurons are early vulnerable to AD. Method: We used quantitative histopathological assessment using multiplex immunofluorescence to quantify the number of NeuN+, T231+, CDH9+, and RORB+ cells in 18 cases across Braak stages 0‐V1. All cases were 8μm thick, formalin‐fixed and paraffin embedded coronal sections of EC. Slides stained with hematoxylin and eosin were used to delineate the EC boundaries and identifying clusters of stellate cells in layer II. Neuronal quantification of EC external layers was done using an in‐house automated cell counting tool with manual quality control and using the ImageJ cell counter plugin. Result: The number of neurons (NeuN+) decreased along the Braak stages II‐VI (p<0.01) (Fig. 1A), whereas the proportion of ptau+ (T231) neurons increased stages II‐VI (p<0.001) (Fig. 1B). CDH9+ neurons had a significantly higher proportion of T231 colocalization in Braak stages II‐IV (p<0.01) and IV‐VI (p<0.05) compared to 0‐II (Fig. 1G). We observed a trend on neuronal loss, but it did not reach statistical significance (Fig. 1C, E). Similar results were observed to the RORB+ neuronal population (Fig. 1 D, F H). Conclusion: CDH9+ and RORB+ cells are more likely to accumulate tau compared to non‐CDH9+ and non‐RORB+ cells. RORB+ and CDH+ cells are more likely to accumulate tau in Braak stages II‐IV, but the relationship is not linear, and the accumulation plateaus in the Braak stages IV‐VI. The trend of CDH9+ and RORB+ cell loss did not reach statistical significance, suggesting this pilot study is still underpowered. The results confirm that CDH9+ and RORB+ cells are selectively vulnerable to tau pathology. [ABSTRACT FROM AUTHOR]

Sorbus commixta is a traditional oriental medicinal plant that grows in East Asian countries such as Korea, Japan and China. The twig of S. commixta has been considered valuable for centuries to treat diseases including asthma, cough and other bronchial disorders. However, the effect of S. commixta twig extract on human skin has not been investigated well. The present study aimed at assessing the antiphotoaging effect of S. commixta twig ethanol extract (STE) on ultraviolet B (UVB)-induced matrix metalloproteinase (MMP) levels and its underlying mechanism in human dermal fibroblasts. In this study, we found that STE (12.5-50 µg mL-1) treatment significantly inhibited UVB-induced MMP-1, MMP-2 and MMP-3 expression, concomitant with a downregulation of intracellular ROS generation. These effects might be associated with a STE-induced inhibition of the mitogen-activated protein kinase (MAPK) pathway. Furthermore, STE also downregulated UVB-induced c-Fos expression in a concentration- dependent manner, but had no inhibitory effect on c-Jun phosphorylation. Taken together, these results indicate that STE may be an antiphotoaging agent and that its effect may occur via its inhibition of MMPs expression and MAPK pathway activation. [ABSTRACT FROM AUTHOR]

Objective: The third generation Intelligent Device for Energy Expenditure and Activity (IDEEA3, MiniSun, CA) has been developed for clinical gait evaluation, and this study was designed to evaluate the accuracy and reliability of IDEEA3 for the gait measurement of lumbar spinal stenosis (LSS) patients. Methods: Twelve healthy volunteers were recruited to compare gait cycle, cadence, step length, velocity, and number of steps between a motion analysis system and a high‐speed video camera. Twenty hospitalized LSS patients were recruited for the comparison of the five parameters between the IDEEA3 and GoPro camera. Paired t‐test, intraclass correlation coefficient, concordance correlation coefficient, and Bland–Altman plots were used for the data analysis. Results: The ratios of GoPro camera results to motion analysis system results, and the ratios of IDEEA3 results to GoPro camera results were all around 1.00. All P‐values of paired t‐tests for gait cycle, cadence, step length, and velocity were greater than 0.05, while all the ICC and CCC results were above 0.950 with P < 0.001. Conclusions: The measurements for gait cycle, cadence, step length, velocity, and number of steps with the GoPro camera are highly consistent with the measurements with the motion analysis system. The measurements for IDEEA3 are consistent with those for the GoPro camera. IDEEA3 can be effectively used in the gait measurement of LSS patients. [ABSTRACT FROM AUTHOR]

Objective: To establish a logistic regression model using surface electromyography (SEMG) parameters for diagnosing the compressed nerve root at L5 or S1 level in patients with lumbar disc herniation (LDH). Methods: This study recruited 24 patients with L5 nerve root compression and 23 patients with S1 nerve root compression caused by LDH from May 2014 to May 2016. SEMG signals from the bilateral tibialis anterior and lateral gastrocnemius were measured. The root mean square (RMS), the RMS peak time, the mean power frequency (MPF), and the median frequency (MF) were analyzed. The accuracy, sensitivity, and specificity values were calculated separately. The areas under the curve (AUC) of the receiver‐operating characteristic (ROC) curve and the kappa value were used to evaluate the accuracy of the SEMG diagnostic model. Results: The accuracy of the SEMG model ranged from 85.71% to 100%, with an average of 93.57%. The sensitivity, specificity, AUC, and kappa value of the logistic regression model were 0.98 ± 0.05, 0.92 ± 0.09, 0.95 ± 0.04 (P = 0.006), and 0.87 ± 0.11, respectively (P = 0.001). The final diagnostic model was: P = 1 − 1 1 + e y; y = 10.76 − (5.95 × TA_RMS Ratio) − (0.38 × TA_RMS Peak Time Ratio) – (5.44 × 44 × LG_RMS Peak Time Ratio). L5 nerve root compression is diagnosed when P < 0.5 and S1 nerve root compression when P ≥ 0.5. Conclusions: The logistic regression model developed in this study showed high diagnostic accuracy in detecting the compressed nerve root (L5 and S1) in these patients with LDH. [ABSTRACT FROM AUTHOR]

Intratumoral heterogeneity at the genetic, epigenetic, transcriptomic, and morphologic levels is a commonly observed phenomenon in many aggressive cancer types. Clonal evolution during tumor formation and in response to therapeutic intervention can be predicted utilizing reverse engineering approaches on detailed genomic snapshots of heterogeneous patient tumor samples. In this study, we developed an extensive dataset for a GBM case via the generation of polyclonal and monoclonal glioma stem cell lines from initial diagnosis, and from multiple sections of distant tumor locations of the deceased patient's brain following tumor recurrence. Our analyses revealed the tissue-wide expansion of a new clone in the recurrent tumor and chromosome 7 gain and chromosome 10 loss as repeated genomic events in primary and recurrent disease. Moreover, chromosome 7 gain and chromosome 10 loss produced similar alterations in mRNA expression profiles in primary and recurrent tumors despite possessing other highly heterogeneous and divergent genomic alterations between the tumors. We identified ETV1 and CDK6 as putative candidate genes, and NFKB (complex), IL1B, IL6, Akt and VEGF as potential signaling regulators, as potentially central downstream effectors of chr7 gain and chr10 loss. Finally, the differences caused by the transcriptomic shift following gain of chromosome 7 and loss of chromosome 10 were consistent with those generally seen in GBM samples compared to normal brain in large-scale patient-tumor data sets. [ABSTRACT FROM AUTHOR]

A series of alkyl sulphobetaine Gemini surfactants C-GSBS ( n = 8, 10, 12, 14, 16) was synthesized, using aliphatic amine, cyanuric chloride, ethylenediamine, N, N′-dimethyl-1,3-propyldiamine and sodium 2-chloroethane sulfonate as main raw materials. The chemical structures were confirmed by FT-IR, H NMR and elemental analysis. The Krafft points differ markedly with different carbon chain length, for C-GSBS, C-GSBS and C-GSBS are considered to be below 0 °C and C-GSBS, C-GSBS are higher than 0 °C but lower than room temperature. Surface-active properties were studied by surface tension and electrical conductivity. Critical micelle concentrations were much lower than dodecyl sulphobetaine (BS-12) and decreased with increasing length of the carbon chain from 8 to 16, and can reach a minimum as low as 5 × 10 mol L for C-GSBS. Effects of carbon chain length and concentration of C-GSBS on crude oil emulsion stability were also investigated and discussed. [ABSTRACT FROM AUTHOR]

ABSTRACT A series of bi-component nonylphenol alkyl sulphonate surfactants with different alkyl chains (C12/ n-NPAS, n = 8, 10, 14, 16) were synthesized through sulphonation-alkylation-neutralization, using a mixture of linear alpha olefins as raw materials. The chemical structures were characterized by FTIR and ESI-MS. The purity values measured by the two-phase titration method were all higher than 0.96 g/g (96 wt%). The effects of the raw materials composition on salinity tolerance, adsorption, and emulsification properties were also investigated. There is marked adsorption amount variation for bi-component surfactants with a strong difference of carbon number of alkyl groups. The salinity tolerance of C12/n-NPAS is about 40 g · L−1 of NaCl, and 0.65 g · L−1 of CaCl2. Compared with petroleum sulphonates (14 g · L−1 of NaCl, 0.08 g · L−1 of CaCl2) and LAS (22 g · L−1 of NaCl, 0.37 g · L−1 of CaCl2), NPAS surfactants show a low adsorption, excellent salinity tolerance, and emulsion stability. [ABSTRACT FROM AUTHOR]

Ni-B amorphous alloy particles were selectively loaded inside and outside of carbon nanotubes (CNTs) to form a series of Ni-B/CNTs amorphous alloy catalysts. The confinement effects of the CNTs on the physicochemical properties of Ni-B/CNTs were investigated. The results show that compared with external loading, the Ni-B active components after internal loading were subjected to the confinement effect, which better inhibited the growth and aggregation of Ni-B particles, forming smaller-size Ni-B particles, and improved the thermal stability of the Ni-B amorphous alloy. Moreover, the Ni-B particles confined in the channels can more efficiently activate hydrogen. During the m-chloronitrobenzene hydrogenation, the Ni-B/CNTs with Ni-B internal loading showed higher catalytic hydrogenation activity than that for Ni-B external loading. High-temperature treatment caused a decrease in the catalytic activity, but the internal loading improved the stability of the catalysts. The internal loading method could effectively reduce the loss of the active component, which contributed to improving the stability of the catalyst. [ABSTRACT FROM AUTHOR]

ABSTRACT Polypyrrole deposited on titanium mesh (PPy-TiM) was fabricated via a galvanostatic method with titanium mesh as the substrate to electrochemically deposit polypyrrole (PPy) doped with p-toluene sulfonate anions. The influence of the deposition time on the characteristics of the PPy-TiM samples was investigated. Then, semitransparent flexible electrochemical capacitors were assembled with the optimal samples of PPy-TiM as electrodes and H3PO4-poly(vinyl alcohol) as the gel electrolyte. The testing results show that PPy in the optimal PPy-TiM electrode had a specific capacitance of about 326 F/g, and the capacitance of the assembled cells still remained unchanged or up even after 20,000 cycles. Just as expected, the cells possessed semitransparent and good flexibility, and three cells connected in series could drive an LED device. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2017 [ABSTRACT FROM AUTHOR]

Aims The main purpose was to verify the potent capacity of Neurotropin® against neuronal damage in hippocampus and to explore its underlying mechanisms. Methods HT22 cells were treated with 40 μmol/L Aβ25-35 in the presence of various concentrations of Neurotropin® or in its absence. The cell viability was assessed with a CCK-8 assay, and flow cytometry was used to measure cell apoptosis, intracellular ROS levels, and mitochondrial membrane potential. Aβ plaques were examined by Bielschowsky silver staining, and the activities of antioxidants were detected in hippocampus of APP/ PS1 mice after Neurotropin® treatment. The expression of proteins, including HIF-1α, Bcl-2, Bax, and MAPKs signaling molecules was evaluated by Western blot. Results Neurotropin® significantly reversed the cell injury induced by Aβ25-35 through increasing cell viability and mitochondrial membrane potential, decreasing intracellular ROS and cell apoptosis of HT22 cells ( P<.05). Furthermore, Neurotropin® markedly reduced the formation of Aβ plaques and upregulated the activities of antioxidants ( P<.05). Additionally, the protein expression of HIF-1α, p- ERK1/2, p- JNK, and p-P38 was significantly inhibited in hippocampus of APP/ PS1 mice. Conclusions Neurotropin® exhibited a potent neuroprotective effect on inhibiting Aβ-induced oxidative damage and alleviating Aβ deposition in hippocampus via modulation of HIF-1α/ MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Background: The anterior hypothalamus contains several sleep‐promoting nuclei, including the suprachiasmatic nucleus (SCN), the key circadian clock in the brain. Sleep disturbances are a common in Alzheimer's disease (AD), but little is known about the profile of AD‐related pathology in the anterior hypothalamic nuclei. Method: We used the GeoMx Digital Spatial Profiling (DSP), an in‐situ spatial proteomics platform (Nanostring) to assess spatially resolved tauopathy and tau‐driven protein alteration in the SCN, supraoptic nucleus (SON), and periventricular nucleus (PV) in the anterior hypothalamus of four postmortem brains from three AD subjects and one control. The profiled regions‐of‐interest were confirmed by immunohistochemistry. Result: All three nuclei showed significantly higher levels of p‐tau 404 and 396 in AD than control, and differential patterns of selective vulnerability for tau, with the SCN, expressing greater p‐tau 404 and 396 levels than the SON. In addition, the p‐tau immunoreactivity corresponds to the DSP data. Interestingly, the PV indicated upregulated β‐amyloid(1‐42) and β‐secretase 1 than others. Conclusion: AD patients revealed increased p‐tau expression in the SCN located in the anterior hypothalamus. Given that tau pathology is one of the main features in AD, altered p‐tau level may lead the SCN and other hypothalamic protein alteration shown in this result, influencing the hierarchical clustering. We suggest tauopathy can be a preceding criterion for tau‐driven hypothalamic protein subpopulation, explaining AD‐driven neurodegeneration and dysfunction such as sleep dysregulation in AD. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effects of surgery and rehabilitation on patients undergoing total knee arthroplasty ( TKA). Methods Twelve patients and 12 healthy controls were enrolled and their clinical scores evaluated by a doctor. Gait data, including walking velocity, stride length, single support time, foot fall and swing power, were collected using a portable gait analyzer from 12 patients before and 6 weeks and 6 months after surgery and from 12 healthy controls. The gait data and clinical scores at selected time points were compared and correlations between gait characteristics and clinical scores assessed. Results Clinical knee and knee function scores increased significantly from before surgery to 6 weeks to 6 months after surgery ( P < 0.001). The only significant differences identified were for single support time on the diseased side between before surgery and 6 months after surgery ( P = 0.031) and for foot fall with the diseased side between 6 weeks and 6 months after surgery ( P = 0.016). Foot fall and speed of the healthy or diseased sides were significantly different in patients at all time points from those of the healthy subjects ( P < 0.05). Single support time on the diseased side was significantly different 6 months after surgery ( P = 0.035) in patients than in healthy controls. Single support time on the healthy side before surgery was significantly different from that of healthy controls ( P = 0.048) and 6 weeks after surgery ( P = 0.042). Stride lengths differed significantly between patients and healthy subjects before surgery (healthy side: P = 0.007; diseased side: P = 0.008) and 6 weeks after surgery (healthy side: P = 0.001; diseased side: P = 0.001), but were not different at 6 months after surgery (healthy side: P = 0.088; diseased side: P = 0.077). The only significant correlations identified were between single support time with the diseased side of patients and their knee ( r = 0.43, P = 0.032) and knee function scores ( r = 0.493, P = 0.012). Conclusions A portable gait analyzer appears to be suitable for evaluating the effects of TKA. Single support time on the diseased side may be a sensitive quantitative index for determining the effect of TKA and rehabilitation. [ABSTRACT FROM AUTHOR]

BACKGROUND Coal fly ash ( CFA) is a solid waste generated during combustion and transformation of coal that causes serious environmental pollution because of the huge amount of emissions and subsequent accumulation. In this work, coal fly ash was selected as a source of silicon and aluminum components to synthesize zeolites Na-P and Na-X. RESULTS High purity zeolites Na-P and Na-X were synthesized under hydrothermal conditions. The influences of an organic steric agent and different sodium salts on the preparation were investigated and the process parameters of the hydrothermal system optimized. The synthesized product was further characterized by XRD, SEM, ICP, FTIR, and BET surface area measurements. Adsorption tests of Na-P and Na-X zeolite for Ni2+ were performed and flame atomic absorption spectrometry ( FAAS) was used for the detailed analysis. CONCLUSION Pretreatment and purification of CFA favors the preparation of pure Na-P and Na-X zeolite. The organic steric agent and different sodium salts were used to decrease the grain size of the product and control the purity and yield, respectively. Zeolite Na-P synthesized with the addition of TEA (triethanolamine) had the best Ni2+ adsorption performance and a hypothesis for Ni2+ adsorption is proposed. Preliminary analysis proved that Van der Waals absorption is the main type of adsorption for the porous zeolite but ion exchange could also occur with the effect of metal ion exchange contributing a maximum of 13.56% to the total adsorption capacity. © 2015 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

A series of Cu/TiO2-SiO2 catalysts were prepared by a sol-gel hydrothermal method and characterized by BET, SEM, TEM, XRD, XPS, and H2-TPR. The catalysts were used for selective hydrogenation of furfural to furfuryl alcohol. Results show that based on the Cu/SiO2 catalyst, introducing a part of TiO2 into the carrier while keeping very large specific surface area would promote the reduction of CuO, inhibit the growth of Cu crystal particles, and improve the dispersity of Cu particles in the catalyst. The electronegativity of Cu is enhanced in the double-loaded Cu/TiO2-SiO2 catalyst, compared with single-loaded Cu/SiO2 or Cu/TiO2 catalysts. The Cu/TiO2-SiO2 catalyst containing 0.40 g/g (40 wt%) TiO2 in the carrier shows high furfural hydrogenation performance. [ABSTRACT FROM AUTHOR]

A series of nonylphenol-substituted alkyl sulfonates (C NPAS, x = 8, 10, 12, 14, 16) with two hydrocarbon chains and two different hydrophilic groups has been synthesized from α-olefins and nonylphenol. The respective products have a 'pseudo-gemini' surfactant structure. The structures of the C NPAS have been characterized by IR, UV, H nuclear magnetic resonance, electrospray ionization mass spectrometry, and elemental analysis. The effects of carbon chain length of the obtained surfactants on properties such as the critical micelle concentrations (CMC) in aqueous solutions, surface tension at the CMC ( γ), and efficiency of adsorption at the water/air interface ( pC) have been determined. The γ of the surfactants first decreased and then increased with increasing length of the carbon chain x, and reached a minimum of 29.25 mN/m at x = 10, which is much lower than that of α-olefin sulfonate (AOS) (33.52 mN/m). The CMC decreased and pC increased with increasing x. The introduction of the hydroxyl group is responsible for multiple molecular conformations at the water/air interface and leads to a greater molecular area A and smaller Γ than those of AOS. [ABSTRACT FROM AUTHOR]

High-speed countercurrent chromatography is a liquid-liquid separation chromatographic technique, which has the unique feature of eliminating irreversible adsorption using liquid support medium, and is widely used in research and development of traditional Chinese medicine, biochemistry, food, environment analysis, and so on. In this review, some new developments of countercurrent chromatography, for instance cross-axis countercurrent chromatography, dual countercurrent chromatography, foam countercurrent chromatography, and pH-zone-refining countercurrent chromatography are presented. Furthermore, the research and progress in high-speed countercurrent chromatography techniques and its application in the separation and purification of terpenoids and saponins are reviewed. [ABSTRACT FROM AUTHOR]