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Developing lightweight composite with reversible switching between microwave (MW) absorption and electromagnetic interference (EMI) shielding is promising yet remains highly challenging due to the completely inconsistent attenuation mechanism for electromagnetic (EM) radiation. Here, a lightweight vanadium dioxide/expanded polymer microsphere composites foam (VO 2 /EPM) is designed and fabricated with porous structures and 3D VO 2 interconnection, which possesses reversible switching function between MW absorption and EMI shielding under thermal stimulation. The VO 2 /EPM exhibits MW absorption with a broad effective absorption bandwidth of 3.25 GHz at room temperature (25 °C), while provides EMI shielding of 23.1 dB at moderately high temperature (100 °C). This reversible switching performance relies on the porous structure and tunability of electrical conductivity, complex permittivity, and impedance matching, which are substantially induced by the convertible crystal structure and electronic structure of VO 2 . Finite element simulation is employed to qualitatively investigate the change in interaction between EM waves and VO 2 /EPM before and after the phase transition. Moreover, the application of VO 2 /EPM is demonstrated with a reversible switching function in controlling wireless transmission on/off, showcasing its excellent cycling stability. This kind of smart material with a reversible switching function shows great potential in next-generation electronic devices., (© 2024 Wiley‐VCH GmbH.)

Cell migration is known to be a fundamental biological process, playing an essential role in development, homeostasis, and diseases. This paper introduces a cell tracking algorithm named HFM-Tracker (Hybrid Feature Matching Tracker) that automatically identifies cell migration behaviours in consecutive images. It combines Contour Attention (CA) and Adaptive Confusion Matrix (ACM) modules to accurately capture cell contours in each image and track the dynamic behaviors of migrating cells in the field of view. Cells are firstly located and identified via the CA module-based cell detection network, and then associated and tracked via a cell tracking algorithm employing a hybrid feature-matching strategy. This proposed HFM-Tracker exhibits superiorities in cell detection and tracking, achieving 75% in MOTA (Multiple Object Tracking Accuracy) and 65% in IDF1 (ID F1 score). It provides quantitative analysis of the cell morphology and migration features, which could further help in understanding the complicated and diverse cell migration processes.

The remarkable properties of carbon nanotubes (CNTs) have led to promising applications in the field of electromagnetic interference (EMI) shielding. However, for macroscopic CNT assemblies, such as CNT film, achieving high electrical and mechanical properties remains challenging, which heavily depends on the tube-tube interactions of CNTs. Herein, we develop a novel strategy based on metal-organic decomposition (MOD) to fabricate a flexible silver-carbon nanotube (Ag-CNT) film. The Ag particles are introduced in situ into the CNT film through annealing of MOD, leading to enhanced tube-tube interactions. As a result, the electrical conductivity of Ag-CNT film is up to 6.82 × 10 5  S m -1 , and the EMI shielding effectiveness of Ag-CNT film with a thickness of ~ 7.8 μm exceeds 66 dB in the ultra-broad frequency range (3-40 GHz). The tensile strength and Young's modulus of Ag-CNT film increase from 30.09 ± 3.14 to 76.06 ± 6.20 MPa (~ 253%) and from 1.12 ± 0.33 to 8.90 ± 0.97 GPa (~ 795%), respectively. Moreover, the Ag-CNT film exhibits excellent near-field shielding performance, which can effectively block wireless transmission. This innovative approach provides an effective route to further apply macroscopic CNT assemblies to future portable and wearable electronic devices., (© 2024. The Author(s).)

This study examines inhibiting galectin 1 (Gal1) as a treatment option for hepatocellular carcinoma (HCC). Gal1 has immunosuppressive and cancer-promoting roles. Our data showed that Gal1 was highly expressed in human and mouse HCC. The levels of Gal1 positively correlated with the stages of human HCC and negatively with survival. The roles of Gal1 in HCC were studied using overexpression (OE) or silencing using Igals1 siRNA delivered by AAV9. Prior to HCC initiation induced by RAS and AKT mutations, lgals1- OE and silencing had opposite impacts on tumor load. The treatment effect of lgals1 siRNA was further demonstrated by intersecting HCC at different time points when the tumor load had already reached 9% or even 42% of the body weight. Comparing spatial transcriptomic profiles of Gal1 silenced and OE HCC, inhibiting matrix formation and recognition of foreign antigen in CD45 + cell-enriched areas located at tumor-margin likely contributed to the anti-HCC effects of Gal1 silencing. Within the tumors, silencing Gal1 inhibited translational initiation, elongation, and termination. Furthermore, Gal1 silencing increased immune cells as well as expanded cytotoxic T cells within the tumor, and the anti-HCC effect of lgals1 siRNA was CD8-dependent. Overall, Gal1 silencing has a promising potential for HCC treatment., Competing Interests: The authors declare no potential competing interests., (© 2024 The Authors.)

Objective: Surveillance algorithms that predict patient decompensation are increasingly integrated with clinical workflows to help identify patients at risk of in-hospital deterioration. This scoping review aimed to identify the design features of the information displays, the types of algorithm that drive the display, and the effect of these displays on process and patient outcomes., Materials and Methods: The scoping review followed Arksey and O'Malley's framework. Five databases were searched with dates between January 1, 2009 and January 26, 2022. Inclusion criteria were: participants-clinicians in inpatient settings; concepts-intervention as deterioration information displays that leveraged automated AI algorithms; comparison as usual care or alternative displays; outcomes as clinical, workflow process, and usability outcomes; and context as simulated or real-world in-hospital settings in any country. Screening, full-text review, and data extraction were reviewed independently by 2 researchers in each step. Display categories were identified inductively through consensus., Results: Of 14 575 articles, 64 were included in the review, describing 61 unique displays. Forty-one displays were designed for specific deteriorations (eg, sepsis), 24 provided simple alerts (ie, text-based prompts without relevant patient data), 48 leveraged well-accepted score-based algorithms, and 47 included nurses as the target users. Only 1 out of the 10 randomized controlled trials reported a significant effect on the primary outcome., Conclusions: Despite significant advancements in surveillance algorithms, most information displays continue to leverage well-understood, well-accepted score-based algorithms. Users' trust, algorithmic transparency, and workflow integration are significant hurdles to adopting new algorithms into effective decision support tools., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

MicroRNA-22 (miR-22) can be induced by beneficial metabolites that have metabolic and immune effects, including retinoic acids, bile acids, vitamin D 3 , and short-chain fatty acids. The tumor suppressor effects of miR-22 have been suggested, but whether miR-22 treats orthotopic hepatocellular carcinoma (HCC) is not established. The role of miR-22 in regulating tumor immunity is also poorly understood. Our data showed that miR-22 delivered by adeno-associated virus serotype 8 effectively treated HCC. Compared with FDA-approved lenvatinib, miR-22 produced better survival outcomes without noticeable toxicity. miR-22 silenced hypoxia-inducible factor 1 (HIF1α) and enhanced retinoic acid signaling in both hepatocytes and T cells. Moreover, miR-22 treatment improved metabolism and reduced inflammation. In the liver, miR-22 reduced the abundance of IL17-producing T cells and inhibited IL17 signaling by reducing the occupancy of HIF1α in the Rorc and Il17a genes. Conversely, increasing IL17 signaling ameliorated the anti-HCC effect of miR-22. Additionally, miR-22 expanded cytotoxic T cells and reduced regulatory T cells (Treg). Moreover, depleting cytotoxic T cells also abolished the anti-HCC effects of miR-22. In patients, miR-22 high HCC had upregulated metabolic pathways and reduced IL17 pro-inflammatory signaling compared with miR-22 low HCC. Together, miR-22 gene therapy can be a novel option for HCC treatment., Competing Interests: Declaration of interests The authors declare no potential conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Low-dimensional transition metal dichalcogenides (TMDs) have unique electronic structure, vibration modes, and physicochemical properties, making them suitable for fundamental studies and cutting-edge applications such as silicon electronics, optoelectronics, and bioelectronics. However, the brittleness, low toughness, and poor mechanical and electrical stabilities of TMD-based films limit their application. Herein, a TaS 2 freestanding film with ultralow void ratio of 6.01% is restacked under the effect of bond-free van der Waals (vdW) interactions within the staggered 2H-TaS 2 nanosheets. The restacked films demonstrated an exceptionally high electrical conductivity of 2,666 S cm -1 , electromagnetic interference shielding effectiveness (EMI SE) of 41.8 dB, and absolute EMI SE (SSE/t) of 27,859 dB cm 2  g -1 , which is the highest value reported for TMD-based materials. The bond-free vdW interactions between the adjacent 2H-TaS 2 nanosheets provide a natural interfacial strain relaxation, achieving excellent flexibility without rupture after 1,000 bends. In addition, the TaS 2 nanosheets are further combined with the polymer fibers of bacterial cellulose and aramid nanofibers via electrostatic interactions to significantly enhance the tensile strength and flexibility of the films while maintaining their high electrical conductivity and EMI SE.This work provides promising alternatives for conventional materials used in EMI shielding and nanodevices., (© 2023. The Author(s).)

MXenes with unique physicochemical properties have shown substantial potential in electromagnetic interference (EMI) shielding. However, the chemical instability and mechanical fragility of MXenes has become a major hurdle for their application. Abundant strategies have been dedicated to improving the oxidation stability of colloidal solution or mechanical properties of films, which always come at the expense of electrical conductivity and chemical compatibility. Here, hydrogen bond (H-bond) and coordination bond are employed to achieve chemical and colloidal stability of MXenes (0.1 mg mL -1 ) by occupying the reaction sites of Ti 3 C 2 T x attacking of water and oxygen molecules. Compared to the Ti 3 C 2 T x , the Ti 3 C 2 T x modified with alanine via H-bond shows significantly improved oxidation stability (at room temperature over 35 days), while the Ti 3 C 2 T x modified with cysteine by synergy of H-bond and coordination bond can be maintained even after 120 days. Simulation and experimental results verify the formation of H-bond and Ti-S bond by a Lewis acid-base interaction between Ti 3 C 2 T x and cysteine. Furthermore, the synergy strategy significantly improves the mechanical strength of the assembled film (up to 78.1 ± 7.9 MPa), corresponding the increment of 203% compared to untreated one, almost without compromising the electrical conductivity and EMI shielding performance., (© 2023 Wiley-VCH GmbH.)

RNA modifications modulate essential cellular functions. However, it is challenging to quantitatively identify the differences in RNA modifications. To further improve the single-molecule sensing ability of nanopores, we propose a machine-learning algorithm called SmartImage for identifying and classifying nanopore electrochemical signals based on a combination of improved graph conversion methods and deep neural networks. SmartImage is effective for nearly all ranges of signal duration, which breaks the limitation of the current nanopore algorithm. The overall accuracy (OA) of our proposed recognition strategy exceeded 90% for identifying three types of RNAs. Prediction experiments show that the SmartImage owns the ability to recognize one modified RNA molecule from 1000 normal RNAs with OA >90%. Thus our proposed model and algorithm hold the potential application in clinical applications., (© 2022 Wiley-VCH GmbH.)

Multifunctional thermal management materials with highly efficient electromagnetic wave (EMW) absorption performance are urgently required to tackle the heat dissipation and electromagnetic interference issues of high integrated electronics. However, the high thermal conductivity (λ) and outstanding EMW absorption performance are often incompatible with each other in a single material. Herein, a through-thickness arrayed NiCo 2 O 4 /graphene oxide/carbon fibers (NiCO@CFs) elastomer with integrated functionalities of high thermal conductivity, highly efficient EMW absorption, and excellent compressibility is reported. The NiCO@CFs elastomer realizes a high out-of-plane thermal conductivity of 15.55 W m -1  K -1 , due to the through-thickness vertically aligned CFs framework. Moreover, the unique horizontal segregated magnetic network effectively reduces the electrical contact between the CFs, which significantly enhances impedance matching of NiCO@CFs elastomer. As a result, the vertically arrayed NiCO@CFs elastomer synchronously exhibits ultrabroad effective absorption bandwidth of 8.25 GHz (9.75-18 GHz) at a thickness of 2.4 mm, good impedance matching, and a minimum reflection loss (RL min ) of -55.15 dB. Given these outstanding findings, the multifunctional arrayed NiCO@CFs elastomer opens an avenue for applications in EMW absorption and thermal management. This strategy of constructing thermal/electrical/mechanical pathways provides a promising way for the high-performance multifunctional materials in electronic devices., (© 2022 Wiley-VCH GmbH.)

The rapid increase of operation speed, transmission efficiency, and power density of miniaturized devices leads to a rising demand for electromagnetic interference (EMI) shielding and thermal management materials in the semiconductor industry. Therefore, it is essential to improve both the EMI shielding and thermal conductive properties of commonly used polyolefin components (such as polyethylene (PE)) in electronic systems. Currently, melt compounding is the most common method to fabricate polyolefin composites, but the difficulty of filler dispersion and high resistance at the filler/filler or filler/matrix interface limits their properties. Here, a fold fabrication strategy was proposed to prepare PE composites by incorporation of a well-aligned, seamless graphene framework premodified with MXene nanosheets into the matrix. We demonstrate that the physical properties of the composites can be further improved at the same filler loading by nanoscale interface engineering: the formation of hydrogen bonds at the graphene/MXene interface and the development of a seamlessly interconnected graphene framework. The obtained PE composites exhibit an EMI shielding property of ∼61.0 dB and a thermal conductivity of 9.26 W m -1 K -1 at a low filler content (∼3 wt %, including ∼0.4 wt % MXene). Moreover, other thermoplastic composites with the same results can also be produced based on our method. Our study provides an idea toward rational design of the filler interface to prepare high-performance polymer composites for use in microelectronics and microsystems.

Electrochemical measurements at the single entity level provide ultra-sensitive tools for the precise diagnosis and understanding of basic biological and chemical processes. By decoding current signatures, single-entity electrochemistry provides abundant information on charges, sizes, shapes, catalytic performances and compositions. The accuracy of single-entity electrochemistry highly relies on advanced instrumentation to achieve the amperometric resolution at the sub-picoampere level and the temporal resolution at the sub-microsecond level. Currently, it is still a challenge for paralleling amplifiers to allow low-noise and high bandwidth single-entity electrochemical measurements. Herein, we developed a low-noise four-channel electrochemical instrumentation that integrates an Au electrode array with amplifiers in the circuit board. With this amplifier array, we achieved a high bandwidth (>100 kHz) electrochemical measurement. The further practical experiments proved the capability of this amplifier array system in acquiring transient signals from both single-molecule detection with an aerolysin nanopore and single Pt nanoparticle catalysis during the dynamic collision process. Paired with appropriate microfluidic array systems, our instrumentation will enable an extraordinarily high-throughput feature for single-entity sensing.

Highly conductive polymer foam with light weight, flexibility, and high-performance electromagnetic interference (EMI) shielding is highly desired in the fields of aerospace, communication, and high-power electronic equipment, especially in the board-level packaging. However, traditional technology for preparing conductive polymer foam such as electroless plating and electroplating involves serious pollution, a complex fabrication process, and high cost. It is urgent to develop a facile method for the fabrication of highly conductive polymer foam. Herein, we demonstrated a lightweight and flexible silver-wrapped melamine foam (Ag@ME) via in situ sintering of metal-organic decomposition (MOD) at a low temperature (200 °C) on the ME skeleton modified with poly(ethylene imine). The Ag@ME with a continuous 3D conductive network exhibits good compressibility, an excellent conductivity of 158.4 S/m, and a remarkable EMI shielding effectiveness of 63 dB in the broad frequency of 8.2-40 GHz covering X-, Ku-, K-, and Ka-bands, while the volume content is only 2.03 vol %. The attenuation mechanism of Ag@ME for EM waves is systematically investigated by both EM simulation and experimental analysis. Moreover, the practical EMI shielding application of Ag@ME in board-level packaging is demonstrated and it shows outstanding near-field shielding performance. This novel strategy for fabrication of highly conductive polymer foam with low cost and non-pollution could potentially promote the practical applications of Ag@ME in the field of EMI shielding.

Introduction: Early identification of patients who may suffer from unexpected adverse events (eg, sepsis, sudden cardiac arrest) gives bedside staff valuable lead time to care for these patients appropriately. Consequently, many machine learning algorithms have been developed to predict adverse events. However, little research focuses on how these systems are implemented and how system design impacts clinicians' decisions or patient outcomes. This protocol outlines the steps to review the designs of these tools., Methods and Analysis: We will use scoping review methods to explore how tools that leverage machine learning algorithms in predicting adverse events are designed to integrate into clinical practice. We will explore the types of user interfaces deployed, what information is displayed, and how clinical workflows are supported. Electronic sources include Medline, Embase, CINAHL Complete, Cochrane Library (including CENTRAL), and IEEE Xplore from 1 January 2009 to present. We will only review primary research articles that report findings from the implementation of patient deterioration surveillance tools for hospital clinicians. The articles must also include a description of the tool's user interface. Since our primary focus is on how the user interacts with automated tools driven by machine learning algorithms, electronic tools that do not extract data from clinical data documentation or recording systems such as an EHR or patient monitor, or otherwise require manual entry, will be excluded. Similarly, tools that do not synthesise information from more than one data variable will also be excluded. This review will be limited to English-language articles. Two reviewers will review the articles and extract the data. Findings from both researchers will be compared with minimise bias. The results will be quantified, synthesised and presented using appropriate formats., Ethics and Dissemination: Ethics review is not required for this scoping review. Findings will be disseminated through peer-reviewed publications., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The transport of molecules and ions through biological nanopores is governed by interaction networks among restricted ions, transported molecules, and residue moieties at pore inner walls. However, identification of such weak ion fluctuations from only few tens of ions inside nanopore is hard to achieve owing to electrochemical measurement limitations. Here, we developed an advanced frequency method to achieve qualitative and spectral analysis of ion interaction networks inside a nanopore. The peak frequency f m reveals the dissociation rate between nanopore and ions; the peak amplitude a m depicts the amount of combined ions with the nanopore after interaction equilibrium. A mathematical model for single-molecule frequency fingerprint achieved the prediction of interaction characteristics of mutant nanopores. This single-molecule frequency fingerprint is important for classification, characterization, and prediction of synergetic interaction networks inside nanoconfinement., (© 2021 Wiley-VCH GmbH.)

Objective: To explore the CT grading method of small opacity profusion of pneumoconiosis, and draw up the corresponding CT reference film. Methods: In December 2019, Three hundred thirty-seven cases of pneumoconosis and suspected pneumoconiosis were examined by chest radiography and Computed Tomography (CT) in the same period. According to Diagnosis of Occupational Pneumoconiosis (GBZ 70-2015) , small opacity profusion of pneumoconiosis in each zone of lung was divided. On CT scans, it was divided into 5 grades of 0, 0+, 1, 2 and 3. Grade 0 corresponded to Sub-grade 0/- and Sub-grade 0/0 of Grade 0 in chest radiograph. Grade 0+ was equivalent to Sub-grade 0/1 of Grade 0. Grade 1, 2, 3 were equivalent to Grade 1, 2 and 3, respectively (including each sub-grade) . The CT image quality of each zone of lung was divided into 1 to 4 levels. Results of level 4 were not included in statistical analyses.Based on the results of small opacity profusion in each zone of lung, consistency analysis was performed between chest radiograph and CT. The selection method of reference films was developed. Based on the types and grades of small opacity, the final reference films were determined. Results: There were 1877 zones of lung with CT image quality from level 1 to 3, including 335 in upper right, 319 in middle right, 284 in lower right, 334 in upper left, 320 in middle left and 286 in lower left. The Kappa values of small opacity profusion in upper right zone, upper left zone, left middle zone, and lower left zone were all between 0.4-0.75. In middle right zone and lower right zone, they were all above 0.75.Among all 6 zones of lung, the diagnostic concordance rates between CT and chest radiograph were all above 80%.The corresponding CT reference films were proposed, including type p and q in Grade 2 and 3, type r in Grade 2, type s and t in Grade 0+ to 3. Conclusion: The CT grading method for small opacity profusion of pneumoconiosis is feasible, and the application value of its reference films needs to be further verified.

Objective: To explore the impacts on weight reduction effect treated with acupoint thread embedding therapy at different tissue levels under ultrasonic guidance., Methods: A total of 70 patients with overweight or obesity were randomized into a shallow-tissue thread embedding group (35 cases, 5 cases dropped off) and a deep-tissue thread embedding group (35 cases, 4 cases dropped off). Under ultrasonic guidance, the thread was embedded in the shallow tissue level and the deep tissue level respectively. The acupoints were Zhongwan (CV 12), Xiawan (CV 10), Shuifen (CV 9), Zhongji (CV 3), etc. The thread embedding therapy was exerted once every 2 weeks, totally for 3 times. Before and 2 weeks after treatment, body mass, body mass index (BMI), waist circumference and hip circumference were recorded in the patients of the two groups separately. After each treatment, the number and the property of blood vessels under each acupoint were detected by ultrasound. Besides, the needling sensation and the intensity were scored and the adverse events were observed after thread embedding therapy., Results: After treatment, the reduction range of body mass, BMI and waist circumference in the deep-tissue thread embedding group were larger than those in the shallow-tissue thread embedding group successively ( P <0.05). The scores of distention and fullness sensation, needling sensation and intensity in the deep-tissue thread embedding group were higher than those in the shallow-tissue thread embedding group successively ( P <0.05). Of 29 cases in the shallow-tissue thread embedding group and 27 cases of the deep-tissue thread embedding group, under at least one acupoint, the vessels were found and distributed unevenly ( P <0.05). There were no adverse events, i.e. bleeding and infection in the two groups., Conclusion: The deep-tissue thread embedding therapy achieves the stronger deqi (needling sensation) and better effect of weight reduction. The acupoint thread embedding therapy under ultrasonic guidance can accurately locate the tissue depth and reduce the incidence of adverse events of thread embedding treatment.

Endoplasmic reticulum (ER) stress has been considered as a promising strategy in developing novel therapeutic agents for cardiovascular diseases through inhibiting cardiomyocyte apoptosis. Protocatechualdehyde (PCA) is a natural phenolic compound from medicinal plant Salvia miltiorrhiza with cardiomyocyte protection. However, the potential mechanism of PCA on cardiovascular ischemic injury is largely unexplored. Here, we found that PCA exerted markedly anti-apoptotic effect in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced H9c2 cells (Rat embryonic ventricular H9c2 cardiomyocytes), which was detected by 3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT), lactate dehydrogenase (LDH), Hoechst 33258 and acridine orange/ethidium bromide (AO/EB) assays. PCA also obviously protected cardiomyocytes in myocardial fibrosis model of mice, which was determined by hematoxylin-eosin (HE) staining and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining. Transcriptomics coupled with bioinformatics analysis revealed a complex pharmacological signaling network especially for PCA-mediated ER stress on cardiomyocytes. Further mechanism study suggested that PCA suppressed ER stress via inhibiting protein kinase R-like ER kinase (PERK), inositol-requiring enzyme1α (IRE1α), and transcription factor 6α (ATF6α) signaling pathway through Western blot, DIOC6 and ER-Tracker Red staining, leading to a protective effect against ER stress-mediated cardiomyocyte apoptosis. Taken together, our observations suggest that PCA is a major component from Salvia miltiorrhiza against cardiovascular ischemic injury by suppressing ER stress-associated PERK, IRE1α and ATF6α signaling pathways., (Copyright © 2020. Published by Elsevier B.V.)

A fundamental question relating to protein folding/unfolding is the time evolution of the folding of a protein into its precisely defined native structure. The proper identification of transition conformations is essential for accurately describing the dynamic protein folding/unfolding pathways. Owing to the rapid transitions and sub-nm conformation differences involved, the acquisition of the transient conformations and dynamics of proteins is difficult due to limited instrumental resolution. Using the electrochemical confinement effect of a solid-state nanopore, we were able to snapshot the transient conformations and trace the multiple transition pathways of a single peptide inside a nanopore. By combining the results with a Markov chain model, this new single-molecule technique is applied to clarify the transition pathways of the β-hairpin peptide, which shows nonequilibrium fluctuations among several blockage current stages. This method enables the high-throughput investigation of transition pathways experimentally to access previously obscure peptide dynamics, which is significant for understanding the folding/unfolding mechanisms and misfolding of peptides or proteins., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Previous studies have suggested that water-soluble polysaccharides from fermented carrot pulp (WSP-p) have stronger anti-diabetic effects than those from un-fermented carrot pulp (WSP-n). This study aimed to improve understanding of these functional differences by comparing their molecular structures. Weight-average molecular weights of WSP-p fractions were lower than those of the corresponding WSP-n fractions. While both WSPs had similar functional groups, more fragmented particles were observed on the surface of large particles of WSP-n than WSP-p. Monosaccharide composition and methylation analysis confirmed that both WSP-p and WSP-n were pectic polysaccharides, containing rhamnogalacturonan-I-type polysaccharides with 1,4-linked α-d-galacturonic acid residues and homogalacturonan regions with 1,4-GalpA linkages. 1 H and 13 C NMR showed that they had similar linkage patterns. These findings suggested that probiotic fermentation of WSP mainly cleaved the linkages between repeating units, and resulted in less polydisperse molecular size distributions., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Cerebral ischemia is accompanied by mitochondrial integrity destruction. Thus, reversion of mitochondrial damage holds great potential for cerebral ischemia therapy. As a crucial Bcl-2 family member, pro-apoptotic Bax protein is a main effector of mitochondrial permeabilization and plays an important role in mitochondrial homeostasis. However, there is still a lack of an effective cerebral protective strategy through selectively targeting Bax. In this study, we reported that natural small-molecule protosappanin A (PTA) showed a significant mitochondrial protective effect on oxygen-glucose deprivation/reperfusion (OGD/R)-induced PC12 cells injury through increasing ATP production and maintaining mitochondrial DNA (mtDNA) content. The mechanism study revealed that PTA selectively induced pro-apoptotic protein Bax degradation, without affecting other Bcl-2 family members such as Bcl-2, Bcl-xl, Bad, Puma, Bid, Bim, and Bik. In addition, we found that PTA promoted the association of autophagosomal marker LC3B to Bax for its degradation via an autophagy-dependent manner but not the ubiquitin-proteasome pathway. Collectively, our findings offered a new pharmacological strategy for maintaining mitochondrial function by inducing autophagic degradation of Bax and also provided a novel drug candidate against ischemic neuronal injury.

Flexible and lightweight high-performance electromagnetic interference shielding materials with minimal thickness, excellent mechanical properties, and outstanding reliability are highly desired in the field of fifth-generation (5G) communication, yet remain extremely challenging to manufacture. Herein, we prepared an ultrathin densified carbon nanotube (CNT) film with superior mechanical properties and ultrahigh shielding effectiveness. Upon complete removal of impurities in pristine CNT film, charge separation in individual CNTs induced by polar molecules leads to strong CNT-CNT attraction and film densification, which significantly improve the electrical conductivity, shielding performance, and mechanical strength. The tensile strength is up to 822 ± 21 MPa, meanwhile the electrical conductivity is as high as 902,712 S/m, and the density is only 1.39 g cm -3 . Notably, the shielding effectiveness is over 51 dB with a thickness of merely 1.85 μm in the broad frequency range of 4-18 GHz, and it reaches to ∼82 dB at 6.36 μm and ∼101 dB at 14.7 μm, respectively. Further, such CNT film exhibits excellent reliability after an extended period in strong acid/alkali, high temperature, and high humidity. It demonstrates the best overall performance among representative shielding materials by far, representing a critical breakthrough in the preparation of shielding film toward applications in wearable electronics and 5G communication.

Objective: To compare the clinical effects of thick-needle therapy (TNT) and acupuncture therapy (AT) on patients with Bell's palsy (BP) at the recovery stage., Methods: A total of 146 eligible participants from 3 hospitals in China were randomized into the TNT group (73 cases) and the AT group (73 cases) using a central randomization. Both groups received Western medicine thrice a day for 4 weeks. Moreover, patients in the TNT group received subcutaneous insertion of a thick needle into Shendao (GV 11) acupoint, while patients in the AT group received AT at acupoints of Cuanzhu (BL 2), Yangbai (GB 14), Dicang (ST 4), Xiaguan (ST 7), Jiache (ST 6), Yingxiang (LI 20) and Hegu (LI 4), 4 times a week, for 4 weeks. Both groups received 2 follow-up visits, which were arranged at 1 month and 3 months after treatment, respectively. The primary outcome measure was House-Brackmann Facial Nerve Grading System (HBFNGS) grade. And the clinical recovery rates of both groups were evaluated according to the HBFNGS grades after treatment. The secondary outcome measures included the facial disability index (FDI) and electroneurogram (EnoG). The adverse events were observed and recorded in both groups., Results: Three cases withdrew from the trial, 2 in the TNT group and 1 in the AT group. There was no signifificant difference in the clinical recovery rates between the TNT and AT groups after 4-week treatment [40.85% (29/71) vs. 34.72% (25/72), P>0.05]. At the 2nd follow-up visit, more patients in the TNT group showed reduced HBFNGS grades than those in the AT group (P<0.01). No significant difference was observed between the two groups in FDI score, EnoG latency and maximum amplitude ratio at all time points (all P>0.05)., Conclusion: The clinical effect of TNT was equivalent to that of AT in patients with BP at recovery stage, while the post-treatment effect of TNT was superior to that of AT. (Registration No. ChiCTR-INR-16008409).

With obesity rate consistently increasing, a strong relationship between obesity and fatty liver disease has been discovered. More than 90% of bariatric surgery patients also have non-alcoholic fatty liver diseases (NAFLDs). NAFLD and non-alcoholic steatohepatitis (NASH), which are the hepatic manifestations of metabolic syndrome, can lead to liver carcinogenesis. Unfortunately, there is no effective medicine that can be used to treat NASH or liver cancer. Thus, it is critically important to understand the mechanism underlying the development of these diseases. Extensive evidence suggests that microRNA 22 ( miR-22 ) can be a diagnostic marker for liver diseases as well as a treatment target. This review paper focuses on the roles of miR-22 in metabolism, steatosis, and liver carcinogenesis. Literature search is limited based on the publications included in the PubMed database in the recent 10 years., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest.

Endothiapepsin is an aspartic proteinase that was first isolated from the plant pathogenic fungus Endothia parasitica. In previous studies, we reported on three endothiapepsin-like proteins in the entomopathogenic fungus Beauveria bassiana; the genes were up-regulated in B. bassiana hyper-virulent strain GXsk1011 at early stage infection in the silkworm. However, whether these proteins play a role in pathogenicity or not remains unknown. In this study, we cloned one protein, BbepnL-1 gene (BBA-07766), that has 98% homology with B. bassiana strain Bb2860, and expressed it in the yeast Pichia pastoris to investigate its function. The endothiapepsin-like protein is a secreted proteinase of molecular weight approximately 40 kDa. It has an N-glycosylation site and a mutation in the C-terminal conserved domain- a Thr was mutated to Gly in B. bassiana GXsk1011 and is different than the endothiapepsin of Endothia parasitica. The recombinant endothiapepsin-like protein showed enzyme activity and degraded the protein components of the silkworm cuticle. To further investigate the activity of the endothiapepsin-like protein, we knocked out the gene BbepnL-1 and showed that the loss of BbepnL-1 reduced the virulence in the silkworm. These results demonstrated that the endothiapepsin-like protein of B. bassiana is a virulence factor., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Histone post-translational modifications (PTMs) are involved in various biological processes such as transcriptional activation, chromosome packaging, and DNA repair. Previous studies mainly focused on PTMs by directly targeting histone-modifying enzymes such as HDACs and HATs. Methods and Results: In this study, we discovered a previously unexplored regulation mechanism for histone PTMs by targeting transcription regulation factor 14-3-3ζ. Mechanistic studies revealed 14-3-3ζ dimerization as a key prerequisite, which could be dynamically induced via an allosteric effect. The selective inhibition of 14-3-3ζ dimer interaction with histone H3 modulated histone H3 PTMs by exposing specific modification sites including acetylation, trimethylation, and phosphorylation, and reprogrammed gene transcription profiles for autophagy-lysosome function and endoplasmic reticulum stress. Conclusion: Our findings demonstrate the feasibility of editing histone PTM patterns by targeting transcription regulation factor 14-3-3ζ, and provide a distinctive PTM editing strategy which differs from current histone modification approaches., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) is a central regulator of mitochondrial biogenesis and metabolism, and its expression is closely related to embryo development. To gain insights into the possible mechanisms of PPARGC1A during early embryogenesis, the development potential, mitochondrial biogenesis, and the culture medium metabolomics of embryos were evaluated when PPARGC1A overexpressed or suppressed in rabbit zygotes. Results showed that different PPARGC1A levels in rabbit zygotes could affect blastocyst percentage, and the expressions of mitochondrial biogenesis and metabolic-related genes, as well as the glutathione and adenosine triphosphate levels during early embryo development. In addition, compared with the controls, 12 and 10 different metabolites involved in carbohydrate, amino acid, and fatty acid metabolism were screened in the 5 day's spent culture medium of PPARGC1A overexpressed and suppressed embryos by gas chromatography-mass spectrometer, respectively. Consistent with these metabolite changes, the transcriptions of genes encoding glucose transporters and fatty acid biosynthetic proteins in the embryos from different groups were regulated by PPARGC1A during rabbit embryo development. Taken together, these data provide evidence that PPARGC1A may regulate early rabbit embryo development through mitochondrial biogenesis and metabolism., (© 2019 Wiley Periodicals, Inc.)

Objective: To observe whether edaravone has a therapeutic and protective effect on retinal injury in diabetic rats through the nuclear factor-κB (NF-κB) pathway., Materials and Methods: The Sprague-Dawley rat model of diabetes was established and divided into diabetes model group (model group) and edaravone treatment group (treatment group). Also, normal control group (control group) was set up. After successful modeling, the blood and retinal tissues of rats were collected. Then, the blood glucose content and serum interleukin-6 (IL-6) were detected. Antioxidant indexes, superoxide dismutase (SOD), and malondialdehyde (MDA), were detected via enzyme-linked immunosorbent assay (ELISA), while the number of corneal nerve fibers was observed microscopically. Moreover, the gene and protein expressions of SOD and NF-κB pathway in tissues were detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and Western blotting., Results: The level of blood glucose in model group was increased compared with that in control group (p<0.05), indicating the successful modeling. The levels of tumor necrosis factor-α (TNF-α), IL-6, and IL-1 were significantly higher in model group than those in control group. In terms of the antioxidant indexes, the level of MDA in model group was significantly higher than that in other two groups, while the level of SOD in treatment group was significantly increased and close to that in control group. Besides, the number of corneal nerve fibers significantly declined in model group, while it was increased in treatment group but still lower than that in control group. According to the gene detection results, the mRNA expression of NF-κB p65 was markedly higher in model group than that in control group, and it was decreased in treatment group, while the mRNA expression of SOD showed the opposite trend. The protein expression of NF-κB p65 was remarkably higher in model group than in control group, was decreased in treatment group, and was close to that in control group, while the protein expression of SOD showed the opposite trend., Conclusions: Edaravone can affect the oxidation and antioxidation through the NF-κB signaling pathway, thereby exerting a therapeutic and protective effect on retinal injury in diabetic rats.

Myocardial fibrosis is associated with cardiovascular remodeling, which is characterized by abnormal collagen architecture. However, there are not yet effective strategies targeting this abnormal pathological process. The purpose of our study is to investigate the effect of protocatechualdehyde (PCA) on myocardial fibrosis for exploring the underlying target protein and molecular mechanism. We found PCA significantly suppressed isoprenaline (ISO)-induced fibrosis and collagen deposition in myocardial tissue. Then, the direct pharmacological target of PCA was identified as collagen I using cellular thermal shift assay (CETSA) coupled with stable isotope labeling with amino acids in cell culture (SILAC) technology. Surface plasmon resonance (SPR) analysis further confirmed the specific binding of PCA with collagen I. Moreover, collagen self-assembly assay and atomic force microscope analysis confirmed that PCA directly modulated collagen conformational dynamics. LC-MS/MS analysis was applied to determine lysine residues as the binding sites of PCA on collagen I by covalently cross-linking reaction. Collectively, our study suggests that PCA controls cardiovascular remodeling by mediating diffuse interstitial myocardial fibrosis. Moreover, directly targeting collagen may be a promising strategy for the treatment of heart failure and resultant myocardial fibrosis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A) acts as a powerful coactivator of many transcriptional factors that relate to granulosa cell (GC) apoptosis. In this study, the miRNAs mediating goat follicular atresia and luteinized granulosa cell (LGC) apoptosis induced by hydrogen peroxide (H 2 O 2 ) via PPARGC1A were investigated. Our results showed that miR-1197-3p targeted PPARGC1A was predicted by bioinformatics algorithm and verified by luciferase reporter assay. In addition, miR-1197-3p promoted goat LGC apoptosis via PPARGC1A through mitochondrial-dependent apoptosis pathway, and these effects could be restored by PPARGC1A overexpression. Moreover, H 2 O 2 -induced LGC apoptosis significantly upregulated miR-1197-3p expression and downregulated PPARGC1A level. Pretreatment of miR-1197-3p inhibitor alleviated LGC apoptosis induced by 400 μM H 2 O 2 for 12 h, and preserved the mitochondrial membrane potential by increasing PPARGC1A expression. In conclusion, miR-1197-3p might act as an essential regulator of goat LGC apoptosis potentially via the mitochondrial-dependent apoptosis pathway by targeting PPARGC1A., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aim: To explore a segmentation algorithm based on deep learning to achieve accurate diagnosis and treatment of patients with retinal fluid., Methods: A two-dimensional (2D) fully convolutional network for retinal segmentation was employed. In order to solve the category imbalance in retinal optical coherence tomography (OCT) images, the network parameters and loss function based on the 2D fully convolutional network were modified. For this network, the correlations of corresponding positions among adjacent images in space are ignored. Thus, we proposed a three-dimensional (3D) fully convolutional network for segmentation in the retinal OCT images., Results: The algorithm was evaluated according to segmentation accuracy, Kappa coefficient, and F 1 score. For the 3D fully convolutional network proposed in this paper, the overall segmentation accuracy rate is 99.56%, Kappa coefficient is 98.47%, and F 1 score of retinal fluid is 95.50%., Conclusion: The OCT image segmentation algorithm based on deep learning is primarily founded on the 2D convolutional network. The 3D network architecture proposed in this paper reduces the influence of category imbalance, realizes end-to-end segmentation of volume images, and achieves optimal segmentation results. The segmentation maps are practically the same as the manual annotations of doctors, and can provide doctors with more accurate diagnostic data.

Bone mesenchymal stem cells (BMSCs) have the capacity to differentiate into germ cells (GCs). This study was conducted to develop a non-integrated method of using RNA transfection to derive putative male GCs from goat BMSCs (gBMSCs) in vitro by overexpressing STRA8, BOULE and DAZL. The gBMSCs were induced by co-transfection these three mRNAs together (mi-SBD group) or sequential transfection according to their expression time order in vivo (mi-S + BD group). After transfection, a small population of gBMSCs transdifferentiated into early germ cell-like cells and had the potential to enter meiosis. These cells expressed primordial germ cell specific genes STELLA, C-KIT and MVH, as well as premeiotic genes DAZL, BOULE, STRA8, PIWIL2 and RNF17. Importantly, the expression level of meiotic marker synaptonemal complex protein 3 significantly increased in these transfected two groups compared with control cells by qRT-PCR, immunofluorescence and western blot analysis (P < 0.05). Moreover, the protein expression of MVH was significantly higher in mi-S + BD group than that in mi-SBD group (P < 0.05). In addition, compared with control group, the methylation rate of imprinted gene H19 decreased in these two transfected group (P < 0.05), and the rate was significantly lower in mi-S + BD group compared with mi-SBD group (P < 0.05). This study helps to understand the mechanisms of action of key genes in GCs differentiation and also provides a novel system for in vitro induction of male GCs from stem cells.

Hippo signaling pathway is essential for tissue development and homeostasis, while its specific role in male reproductive tract development is still unclear. The objective of this study is to elucidate the localization and expressions of key Hippo pathway components (MST1/2, LATS1/2 and YAP1) in male reproductive tract (testis, epididymis, and ductus deferens) of prepubertal (3-month-old) and postpubertal (9-month-old) Hu sheep, as well as in the cauda epididymal and ejaculated spermatozoa. Results showed that the Hippo pathway proteins were diversely localized in male reproductive tract portions, and most of their expression levels increased during sheep testicular maturation. In addition, these Hippo components were mainly localized and highly expressed in ejaculated spermatozoa compared with cauda epididymal spermatozoa. In ejaculated spermatozoa, LATS1 was localized in the acrosomal head region, and LATS2 and YAP1 were expressed in the midpiece part. Taken together, the presence of Hippo signaling cascade in the pubertal development of male reproductive tract and spermatogenesis of Hu sheep, provides new insights on the function of these components in the process of male sexual maturation, capacitation and fertilization., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Caesalpinia sappan L. ( C. sappan ) is a traditional Chinese medicinal plant. The dried heartwood of C. sappan (also known as Sappan wood) has been widely used for the folkloric medical treatment of ischemic cerebral stroke in China. However, the detailed underlying pharmacological mechanism still remains largely unexplored. Methods: In this study, a middle cerebral artery occlusion (MCAO) rat model was employed to elucidate the mechanism of the anti-cerebral ischemic effects of C. sappan ethanolic extract (CEE). Moreover, systemic multi-target identification coupled with gene ontology biological process (GO BP) and reactome pathway analysis was used to investigate the potential neuroprotective mechanism. Furthermore, the presumed mechanism was confirmed through biological analysis by determining the effects of CEE on the identified signaling pathways in PC12 cells model-induced by oxygen-glucose deprivation/reperfusion (OGD/R). Results: Our study demonstrates that CEE (both through in vivo administration at a dosage of 300 mg/kg and through in vitro incubation at a dosage of 2.4 μg/mL) is a neuroprotective agent that can effectively inhibit neuronal damage, promote synaptic generation, and suppress the activation of neutrophils, microglia, and astrocytes. Moreover, the neuroprotective mechanism of CEE is mediated via regulating 150 potential target proteins, which are associated with 6 biological processes and 10 pathways, including JAK-STAT, HSP90 and DNA damage/telomere stress. Conclusion: CEE can exert neuroprotective effect through multi-target pharmacological mechanisms to prevent ischemia/reperfusion-induced cerebral injury.

It has been found that probiotic-fermented carrot pulp has a beneficial effect in reducing blood glucose, more so than unfermented pulp. This paper explores the reason for this by looking at fermentation-induced changes in nutritional components and hypoglycemic effects of its polysaccharides. Micronutrient content showed minor changes, except for titratable acidity. Fat and protein decreased, while total carbohydrates increased. These polysaccharides are pectinic, and the number of total polysaccharides rose after fermentation. Scanning electron microscopy showed that the morphology changed from filamentous solid to spiral. The molecular weight of water-soluble polysaccharide (WSP) diminished after fermentation, while those of acid- and alkali-soluble polysaccharides increased. WSP had stronger hydroxyl radical scavenging activity in vitro, and WSP from probiotic-fermented carrot pulps showed better hypoglycemic effects than WSP from non-fermented carrot pulps in animal experiments. Thus, the fermentation-induced improvement in diabetes control from fermented carrot pulp probably arises from its WSP.

Nanopore analysis is a powerful technique for single molecule analysis by virtue of its electrochemically confined effects. As a single molecule translocates through the nanopore, the featured ionic current pattern on the time scale contains single molecule characteristics including volume, charge, and conformational properties. Although the characteristics of a single molecule in a nanopore have been written to the featured ionic current, extracting the dynamic information from a complex current trace is still a big challenge. Here, we present an applicable nanopore analysis method employing the Hilbert-Huang Transform (HHT) to study the vibrational features and interactions of a single molecule during the dynamic translocation process through the confined space of a nanopore. The HHT method is specially developed for analyzing nonlinear and non-stationary data that is highly compatible with nanopore data with a high frequency resolution. To provide proof-of-concept, we applied HHT to measure the frequency response for the wild-type (WT) aerolysin and mutant K238E aerolysin nanopores with and without the presence of poly(dA)4, respectively. The energy-frequency-time distribution spectra demonstrate that the biological nanopore contributes greatly to the characteristics of the high frequency component (>2 kHz) in the current recording. Our results suggest that poly(dA)4 undergoes relatively more consistent and confined interactions with K238E than WT, leading to a prolonging of the duration time. Therefore, the characteristics in frequency analysis could be regarded as an "single-molecule ionic spectrum" inside the nanopore, which encodes the detailed behaviours of single-molecule weak interactions.

Motivated by the unique structure and outstanding properties of graphene, three-dimensional (3D) graphene-based polymer nanocomposites (3D-GPNCs) are considered as new generation materials for various multi-functional applications. This review presents an overview of the preparation, properties and applications of 3D-GPNCs. Three main approaches for fabricating 3D-GPNCs, namely 3D graphene based template, polymer particle/foam template, and organic molecule cross-linked graphene, are introduced. A thorough investigation and comparison of the mechanical, electrical and thermal properties of 3D-GPNCs are performed and discussed to understand their structure-property relationship. Various potential applications of 3D-GPNCs, including energy storage and conversion, electromagnetic interference shielding, oil/water separation, and sensors, are reviewed. Finally, the current challenges and outlook of these emerging 3D-GPNC materials are also discussed.

Metal-based materials with exceptional intrinsic conductivity own excellent electromagnetic interference (EMI) shielding performance. However, high density, corrosion susceptibility, and poor flexibility of the metal severely restrict their further applications in the areas of aircraft/aerospace, portable and wearable smart electronics. Herein, a lightweight, flexible, and anticorrosive silver nanowire wrapped carbon hybrid sponge (Ag@C) is fabricated and employed as ultrahigh efficiency EMI shielding material. The interconnected Ag@C hybrid sponges provide an effective way for electron transport, leading to a remarkable conductivity of 363.1 S m -1 and superb EMI shielding effectiveness of around 70.1 dB in the frequency range of 8.2-18 GHz, while the density is as low as 0.00382 g cm -3 , which are among the best performances for electrically conductive sponges/aerogels/foams by far. More importantly, the Ag@C sponge surprisingly exhibits super-hydrophobicity and strong corrosion resistance. In addition, the hybrid sponges possess excellent mechanical resilience even with a large strain (90% reversible compressibility) and an outstanding cycling stability, which is far better than the bare metallic aerogels, such as silver nanowire aerogels and copper nanowire foams. This strategy provides a facile methodology to fabricate lightweight, flexible, and anticorrosive metal-based sponge for highly efficient EMI shielding applications., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: At the point of care, evidence from randomized controlled trials (RCTs) is underutilized in helping clinicians meet their information needs., Objective: To design interactive visual displays to help clinicians interpret and compare the results of relevant RCTs for the management of a specific patient, and to conduct a formative evaluation with physicians comparing interactive visual versus narrative displays., Methods: We followed a user-centered and iterative design process succeeded by development of information display prototypes as a Web-based application. We then used a within-subjects design with 20 participants (8 attendings and 12 residents) to evaluate the usability and problem-solving impact of the information displays. We compared subjects' perceptions of the interactive visual displays versus narrative abstracts., Results: The resulting interactive visual displays present RCT results side-by-side according to the Population, Intervention, Comparison, and Outcome (PICO) framework. Study participants completed 19 usability tasks in 3 to 11 seconds with a success rate of 78% to 100%. Participants favored the interactive visual displays over narrative abstracts according to perceived efficiency, effectiveness, effort, user experience and preference (all P values <.001)., Conclusions: When interpreting and applying RCT findings to case vignettes, physicians preferred interactive graphical and PICO-framework-based information displays that enable direct comparison of the results from multiple RCTs compared to the traditional narrative and study-centered format. Future studies should investigate the use of interactive visual displays to support clinical decision making in care settings and their effect on clinician and patient outcomes., (©Jiantao Bian, Charlene Weir, Prasad Unni, Damian Borbolla, Thomas Reese, Yik-Ki Jacob Wan, Guilherme Del Fiol. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 25.06.2018.)

Pre-implantation embryo metabolism demonstrates distinctive characteristics associated with the development potential of embryos. We aim to determine if metabolic differences correlate with embryo morphology. In this study, gas chromatography - mass spectroscopy (GC-MS)-based metabolomics was used to assess the culture media of goat cloned embryos collected from high-quality (HQ) and low-quality (LQ) groups based on morphology. Expression levels of amino acid transport genes were further examined by quantitative real-time PCR. Results showed that the HQ group presented higher percentages of blastocysts compared with the LQ counterparts (P < 0.05). Metabolic differences were also present between HQ and LQ groups. The culture media of the HQ group showed lower levels of valin, lysine, glutamine, mannose and acetol, and higher levels of glucose, phytosphingosine and phosphate than those of the LQ group. Additionally, expression levels of amino acid transport genes SLC1A5 and SLC3A2 were significantly lower in the HQ group than the LQ group (P < 0.05, respectively). To our knowledge, this is the first report which uses GC-MS to detect metabolic differences in goat cloned embryo culture media. The biochemical profiles may help to select the most in vitro viable embryos., (© 2017 Japanese Society of Animal Science.)

Artemisia rupestris is a traditional medicine in Uygur and Kazak in Xinjiang Province, mainly distributed in the territory of Xinjiang Altai area, Tianshan mountains and the Kunlun mountains, growing at an altitude of 1 500 to 4 000 meters of grassland and forest areas. As the broad research on chemical constituents, pharmacological activity, the effective components of A. rupestris have attracted the interest to make up new drugs. Based on the latest research from A. rupestris, identification and geographic distribution, chemical constituents, pharmacological effects, clinical applications were summarized in this article, in the view of Medicinal Ethnobotany. At the same time, some suggestions were proposed for future research., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Targets group identification in complex Chinese medicine system is a key step for revealing the potential mechanism of Chinese medicine. The solid beads with magnetic core and benzophenone-modified surface were made in our study, and then benzophenone was activated and cross-linked with the C-H bonds of chemical compositions in Chinese medicines under UV excitation. Thus the chemical compositions of modified Wuzi Yanzong pill(MWP) were linked to the solid bead surface, and enriched the neuroprotective targets group of MWP after being co-incubated with nerve cell lysate. We performed proteomics analysis on these targets and discovereda total of 32 potential binding targets. KEGG analysis revealed that these targets were mainly associated with Hippo and Cell cycle signaling pathways, suggesting that MWP might be involved in regulating the proliferation and differentiation of neural stem cells. Our findings elucidate the potential targets and mechanism of MWP on anti-dementia and neuroprotection, and further providean approach for investigating the targets group in complex Chinese medicine system. This novel method may provide methodological references for exploring the pharmacological mechanism of Chinese medicinal formulae in the future., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Baoyuan decoction (BYD) is a well-known traditional Chinese medicine formula for coronary heart disease with Qi deficiency. However, the detailed pharmacological mechanism of BYD is still unknown because of its complicated chemical compositions. In this study, we synthesized a kind of solid beads with benzophenone groups on its surface. Benzophenone can be activated and chemically cross-linked with the C-H bonds of the chemical compositions in BYD (BYD beads) under UV activation. We thus captured all the target proteins from mouse heart tissue lysates by using BYD beads. Based on proteomics analysis, we discovered totally 46 potential binding target proteins, most of which were located in mitochondria. KEGG analysis revealed that these target proteins were mainly associated with TCA cycle and amino acid metabolism signaling pathways, suggesting that the cardioprotection of BYD might be associated with regulating mitochondrial function and energy production. Moreover, JC-1 staining analysis also confirmed the protective effect of BYD on mitochondrial damage. In summary, our findings elucidated the potential mechanism of BYD on cardioprotection through "target fishing" strategy, and further explained its traditional efficacy in the molecular level. In addition, we also provide an approach for investigating the target group of complicated compositions in Chinese herbal formula. This novel method may provide a methodological reference for exploring the pharmacological mechanism of traditional Chinese formula in the future., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

During goat follicular development, abnormal expression of nuclear respiratory factor 1 ( NRF1 ) in granulosa cells may drive follicular atresia with unknown regulatory mechanisms. In this study, we investigated the effects of NRF1 on steroidogenesis and cell apoptosis by overexpressing or silencing it in goat luteinized granulosa cells (LGCs). Results showed that knockdown of NRF1 expression significantly inhibited the expression of STAR and CYP19A1 , which are involved in sex steroid hormones synthesis, and led to lower estrogen levels. Knockdown of NRF1 resulted in an increased percentage of apoptosis, probably due to the release of cytochrome c from mitochondria, accompanied by upregulating mRNA and protein levels of apoptosis-related markers BAX, caspase 3 and caspase 9. These data indicate that NRF1 might be related with steroidogenesis and cell apoptosis. Furthermore, NRF1 silence reduced mitochondrial transcription factor A ( TFAM ) transcription activity, mtDNA copy number and ATP level. Simultaneously, knockdown of NRF1 suppressed the transcription and translation levels of SOD, GPx and CAT, decreased glutathione level and increased 8-OHdG level. However, the overexpression of NRF1 in LGCs or gain of TFAM in NRF1 silenced LGCs increased the expression of genes involved in mitochondrial function and biogenesis, and elevated the antioxidant stress system and steroids synthesis. Taken together, aberrant expression of NRF1 could induce mitochondrial dysfunction and disturb the cellular redox balance, which lead to disturbance of steroid hormone synthesis, and trigger LGC apoptosis through the mitochondria-dependent pathway. These findings will be helpful for understanding the role of NRF1 in goat ovarian follicular development and atresia., (© 2017 Society for Reproduction and Fertility.)

Introduction: Biosamples and associated clinical data accelerate translational and clinical research discoveries. A lack of high quality biosamples both stalls projects and limits research advances. In this study, we targeted a wide audience of University of California (UC) biobanking stakeholders who were either involved with the collection or the utilization of biosamples to assess the scope of their biobanking activities and their interest in virtual biobanking or cooperating in the formation of the UC-wide biorepository., Materials and Methods: Each institutional review board from the five UC medical campuses' provided a dataset of potential researchers involved with biobanking. Once identified, a brief six item web-based questionnaire was administered electronically to these researchers., Results: Most survey participants (80%) responded "yes" (n = 348) that they were actively collecting biosamples for research, and 68% of participants indicated they would either definitely (30%, n = 131) or maybe (38%, n = 166) request biosample materials now or within the next year. An equal proportion of participants responded yes (42% or n = 184) and maybe (42% or n = 182) when asked if they would voluntarily contribute specimens to a UC-wide virtual biobank., Discussion: The results presented above show high levels of support among UC biobanking stakeholders for both requesting material from and contributing material to a UC-wide virtual biobank. In addition, a considerable number of individual researchers on our five UC medical campuses are conducting biospecimen research (i.e., well over n = 435 respondents).

Beauveria bassiana is an important entomopathogenic fungus which not only widely distributes in the environment but also shows phenotypic diversity. However, the mechanism of pathogenic differences among natural B. bassiana strains has not been revealed at transcriptome-wide level. In the present study, in order to explore the mechanism, two B. bassiana strains with different pathogenicity were isolated from silkworms (Bombyx mori L.) and selected to analyze the gene expression of early stage by culturing on cuticle extracts of the silkworm and using RNA-sequencing technique. A total of 2108 up-regulated and 1115 down-regulated genes were identified in B. bassiana strain GXsk1011 (hyper-virulent strain) compared with B. bassiana strain GXtr1009 (hypo-virulent strain), respectively. The function categorization of differential expressed genes (DEGs) showed that most of them involved in metabolic process, biosynthesis of secondary metabolites, catalytic activity, and some involved in nutrition uptake, adhesion and host defense were also noted. Based on our data, distinct pathogenicity among different strains of B. bassiana may largely attribute to unique gene expression pattern which differed at very early infection process. Most of the genes involved in conidia adhesion, cuticle degradation and fungal growth were up-regulated in hyper-virulent B. bassiana strain GXsk1011. Furthermore, in combination with fungal growth analysis, our research provided a clue that fungal growth may also play an important role during early infection process. The results will help to explain why different B. bassiana strains show distinct pathogenicity on the same host even under same condition. Moreover, the transcriptome data were also useful for screening potential virulence factors., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Manual acupuncture (MA) manipulations are one of the key factors influencing acupuncture effects in traditional Chinese medicine theory. Different MA manipulations contain different stimulating parameters, thus generating different acupuncture responses or effects. Evidence has demonstrated that acupuncture is effective for functional dyspepsia (FD). However, the effects of different stimulating parameters of MA manipulations on FD remain unclear., Methods/design: This study is a randomized controlled trial with a four-arm, parallel-group structure. Patients with FD with epigastric pain syndrome (EPS) will be included and randomly allocated into four groups: three MA manipulation groups (separately treated with a frequency of 1 Hz, 2 Hz, or 3 Hz) and a control group. All groups will receive omeprazole as a basic treatment and acupuncture: in the MA manipulation groups, the needles will be manipulated manually with three different frequencies on the basis when de qi is reached, while in the control group, the needles will be inserted without any manipulation. All patients will receive acupuncture treatment of five consecutive sessions per week for 2 weeks and be followed up at 4, 8, and 12 weeks. The primary outcomes of the study include patients' response to the treatment. The secondary outcomes include dyspeptic symptoms, quality of life, mental status, fasting serum gastrin, motilin, and ghrelin concentrations, and adverse events. The protocol was approved by the Ethics committee of the First Affiliated Hospital of Zhejiang Chinese Medical University (2016-K-057-01)., Discussion: The aim of this study is to evaluate the efficacy and safety of MA manipulations with different stimulating parameters (different frequencies) on EPS in patients with FD., Trial Registration: Chinese Clinical Trial Registry, ChiCTR-IOR-16008189 . Registered on 30 March 2016.

Healthcare organizations use care pathways to standardize care, but once developed, adoption rates often remain low. One challenge for usage concerns clinicians' difficulty in accessing guidance when it is most needed. Although the HL7 'Infobutton Standard' allows clinicians easier access to external references, access to locally-developed resources often requires clinicians to deviate from their normal electronic health record (EHR) workflow to use another application. To address this gap between internal and external resources, we reviewed the literature and existing practices at the University of Utah Health Care. We identify the requirements to meet the needs of a healthcare enterprise and clinicians, describe the design and development of a prototype to aggregate both internal and external resources from within or outside the EHR, and evaluated strengths and limitations of the prototype. The system is functional but not implemented in a live EHR environment. We suggest next steps and enhancements.

Baicalein, a major flavonoid, possesses anticancer and anti-inflammatory activity. The aim of the study is to explore the efficiency of combination therapy with baicalein and taxol, as well as the molecular mechanism on antitumor activity. Human ovarian cancer cells were treated with different concentration of baicalein for 48 h, and cell viability was determined by MTT assay. Baicalein inhibited cell proliferation of ovarian cancer cells, and IC50 value of baicalein in A2780 cells, SKOV3 cells, and OVCAR cells was 46.23, 60.68, and 38.03 μM, respectively. The ovarian cancer cells were treated with 10 μM of baicalein combined with increasing concentration of taxol for 48 h, and the results demonstrated that combination therapy with baicalein and taxol had much higher antitumor effects compared with the monotherapy. The molecular mechanisms involving in combination therapy promoted the caspase-3 activity then leading to cleavage of poly-ADP-ribose polymerase, which increased the cell apoptosis of ovarian cancer cells. Moreover, Z-VAD-FMK treatment partially decreased the baicalein-induced proliferation inhibition in human ovarian cancer cells. Furthermore, baicalein induced apoptosis through activation of the activities of caspase-3,-9, and increased cytoplasmic cytochrome C release. Importantly, baicalein inhibited the growth of A2780 cells by inhibiting Akt/β-catenin signaling pathway. In conclusion, our result revealed that baicalein combinated with taxol at low concentrations could exert synergistic antitumor effects in ovarian cancer cells through mitochondria-mediated cell apoptosis and Akt/β-catenin signaling pathway. Baicalein has a promising potential to be developed as an antitumor compound, and combination therapy of baicalein and taxol exhibits an antitumor potential in clinical therapy for human ovarian cancers.

During goat follicular development, abnormal expression of peroxisome proliferator- activated receptor gamma coactivator-1 alpha (PGC-1α) in granulosa cells (GCs) may contribute to follicular atresia with unknown regulatory mechanisms. In this study, we investigate the effect of ectopic expression or interference of PGC-1α on cell apoptosis of goat first passage granulosa cells (FGCs) in vitro. The results indicate that PGC-1α silencing by short hairpin RNA (shRNA) in goat FGCs significantly reduced mitochondrial DNA (mtDNA) copy number (P < 0.05), changed mitochondria ultrastructure, and induced cell apoptosis (P < 0.05). The transcription and translation levels of the apoptosis-related genes BCL-2-associated X protein (BAX), caspase 3, and caspase 9 were significantly up-regulated (P < 0.05, respectively). Moreover, the ratio of BAX/B-cell lymphoma 2 (BCL-2) was reduced (P < 0.05), and the release of cytochrome c (cyt c) and lactate dehydrogenase (LDH) was significantly enhanced (P < 0.05, respectively) in PGC-1α interference goat FGCs. Furthermore, the expression of anti-oxidative related genes superoxide dismutase 2 (SOD2), glutathione peroxidase (GPx) and catalase (CAT) was down-regulated (P < 0.05, respectively) and the activity of glutathione/glutathione disulfide (GSH/GSSG) was inhibited (P < 0.05). While enforced expression of PGC-1α increased the levels of genes involved in the regulation of mitochondrial function and biogenesis, and enhanced the anti-oxidative and anti-apoptosis capacity. Taken together, our results reveal that lack of PGC-1α may lead to mitochondrial dysfunction and disrupt the cellular redox balance, thus resulting in goat GCs apoptosis through the mitochondria-dependent apoptotic pathway.