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Mitochondria are central to endothelial cell activation and angiogenesis, with the RNA polymerase mitochondrial (POLRMT) serving as a key protein in regulating mitochondrial transcription and oxidative phosphorylation. In our study, we examined the impact of POLRMT on angiogenesis and found that its silencing or knockout (KO) in human umbilical vein endothelial cells (HUVECs) and other endothelial cells resulted in robust anti-angiogenic effects, impeding cell proliferation, migration, and capillary tube formation. Depletion of POLRMT led to impaired mitochondrial function, characterized by mitochondrial depolarization, oxidative stress, lipid oxidation, DNA damage, and reduced ATP production, along with significant apoptosis activation. Conversely, overexpressing POLRMT promoted angiogenic activity in the endothelial cells. In vivo experiments demonstrated that endothelial knockdown of POLRMT, by intravitreous injection of endothelial specific POLRMT shRNA adeno-associated virus, inhibited retinal angiogenesis. In addition, inhibiting POLRMT with a first-in-class inhibitor IMT1 exerted significant anti-angiogenic impact in vitro and in vivo. Significantly elevated expression of POLRMT was observed in the retinal tissues of streptozotocin-induced diabetic retinopathy (DR) mice. POLRMT endothelial knockdown inhibited pathological retinal angiogenesis and mitigated retinal ganglion cell (RGC) degeneration in DR mice. At last, POLRMT expression exhibited a substantial increase in the retinal proliferative membrane tissues of human DR patients. These findings collectively establish the indispensable role of POLRMT in angiogenesis, both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions This study aimed to investigate whether flow fluid shear stress (FFSS)‐mediated signal transduction affects the function of Piezo1 ion channel in chondrocyte and to further explore the role of mechanical overloading in development of temporomandibular joint osteoarthritis (TMJ OA).Immunohistochemical staining was used to determine the expression of Piezo1 in TMJ OA tissue collected from rat unilateral anterior crossbite (UAC) models. Chondrocytes harvested from normal adult SD rats were treated with FFSS (0, 4, 8, 12 dyn/cm2) in vitro. Immunofluorescent staining, real‐time polymerase chain reaction, western blotting, flow cytometry and phalloidin assay were performed to detect the changes of cellular morphology as well as the expression of Piezo1 and certain pro‐inflammatory and degradative factors in chondrocyte.Immunohistochemical analysis revealed that significantly increased Piezo1 expression was associated with UAC stimulation (p < .05). As applied FFSS escalated (4, 8 and 12 dyn/cm2), the expression levels of Piezo1, ADAMTS‐5, MMP‐13 and Col‐X gradually increased, compared with the non‐FFSS group (p < .05). Administering Piezo1 ion channel inhibitor to chondrocytes beforehand, it was observed that expression of ADAMTS‐5, MMP‐13 and Col‐X was substantially decreased following FFSS treatment (p < .05) and the effect of cytoskeletal thinning was counteracted. The activated Piezo1 ion channel enhanced intracellular Ca2+ excess in chondrocytes during abnormal mechanical stimulation and the increased intracellular Ca2+ thinned the cytoskeleton of F‐actin.Mechanical overloading activates Piezo1 ion channel to promote pro‐inflammation and degradation and to increase Ca2+ concentration in chondrocyte, which may eventually result in TMJ OA. [ABSTRACT FROM AUTHOR]

Efficient intracellular delivery of protein drugs is critical for protein therapy. The combination of protein drugs with chemotherapeutics represents a promising strategy in enhancing anti-cancer effect. However, co-delivery systems for efficient delivery of these two kinds of drugs are still lacking because of their different properties. Herein, we show a well-designed delivery system based on dynamic covalent bond for efficient intracellular co-delivery of ribonuclease A (RNase A) and doxorubicin (DOX). Two polymers, PEG-b-P(Asp-co-AspDA) and PAE-b-P(Asp-co-AspPBA), and two 2-acetylphenylboronic acid (2-APBA)-functionalized drugs, 2-APBA-RNase A and 2-APBA-DOX, self-assemble into mixed-shell nanoparticles (RNase A/DOX@MNPs) via dynamic phenylboronic acid (PBA)-catechol bond between PBA and dopamine (DA) moieties. The PBA-catechol bond endows the nanoparticles with high stability and excellent stimulus-responsive drug release behavior. Under the slight acidic environment at tumor tissue, RNase A/DOX@MNPs are positively charged, promoting their endocytosis. Upon cellular uptake into endosome, further protonation of PAE chains leads to the rupture of endosomes because of the proton sponge effect and the cleavage of PBA-catechol bond promotes the release of two drugs. In cytoplasm, the high level of GSH removed the modification of 2-APBA on drugs. The restored RNase A and DOX show a synergistic and enhanced antic-cancer effect. This system may be a promising platform for intracellular co-delivery of protein drugs and chemotherapeutics. [ABSTRACT FROM AUTHOR]

• The biological functions of m1A modification can provide new targets for drug development. • Accurately predicting N1-Methyladenosine (m1A) at the single-molecule resolution would be crucial. • Our method achieved single-molecule and single-base resolution profiling of m1A RNA methylation using Oxford nanopore direct RNAs sequencing technology. • We tested our method on both IVT and HEK293 datasets and achieved good performance (average AUC = 0.9689, AUPR = 0.8769, accuracy = 0.9474, MCC = 0.7571, F1-Score = 0.7823) • Our model and code are freely available from GitHub (https://github.com/BernieeeX/m1a-prediction). With the recent advanced direct RNA sequencing technique that proposed by the Oxford Nanopore Technologies, RNA modifications can be detected and profiled in a simple and straightforward manner. Majority nanopore-based modification studies were devoted to those popular types such as m6A and pseudouridine. To address current limitations on studying the crucial regulator, m1A modification, we conceived this study. We have developed an integrated computational workflow designed for the detection of m1A modifications from direct RNA sequencing data. This workflow comprises a feature extractor responsible for capturing signal characteristics (such as mean, standard deviations, and length of electric signals), a single molecule-level m1A predictor trained with features extracted from the IVT dataset using classical machine learning algorithms, a confident m1A site selector employing the binomial test to identify statistically significant m1A sites, and an m1A modification rate estimator. Our model achieved accurate molecule-level prediction (Average AUC = 0.9689) and reliable m1A site detection and quantification. To show the feasibility of our workflow, we conducted a study on in vivo transcribed human HEK293 cell line, and the results were carefully annotated and compared with other techniques (i.e., Illumina sequencing-based techniques). We believed that this tool will enabling a comprehensive understanding of the m1A modification and its functional mechanisms within cells and organisms. [ABSTRACT FROM AUTHOR]

Purposes: We previously reported an unexpected phenomenon that shaking stress could cause more protein degradation in freeze-dried monoclonal antibody (mAb) formulations than liquid ones (J Pharm Sci, 2022, 2134). The main purposes of the present study were to investigate the effects of shaking stress on protein degradation and sub-visible particle (SbVP) formation in freeze-dried mAb formulations, and to analyze the factors influencing protein degradation during production and transportation. Methods: The aggregation behavior of mAb-X formulations during production and transportation was simulated by shaking at a rate of 300 rpm at 25°C for 24 h. The contents of particles and monomers were analyzed by micro-flow imaging, dynamic light scattering, size exclusion chromatography, and ultraviolet − visible (UV–Vis) spectroscopy to compare the protective effects of excipients on the aggregation of mAb-X. Results: Shaking stress could cause protein degradation in freeze-dried mAb-X formulations, while surfactant, appropriate pH, polyol mannitol, and high protein concentration could impact SbVP generation. Water content had little effect on freeze-dried protein degradation during shaking, as far as the water content was controlled in the acceptable range as recommended by mainstream pharmacopoeias (i.e., less than 3%). Conclusions: Shaking stress can reduce the physical stability of freeze-dried mAb formulations, and the addition of surfactants, polyol mannitol, and a high protein concentration have protective effects against the degradation of model mAb formulations induced by shaking stress. The experimental results provide new insight for the development of freeze-dried mAb formulations. [ABSTRACT FROM AUTHOR]

Rotator cuff tear (RCT) is a common shoulder disorder related to pain and dysfunction. However, the pathological mechanism of RCT remains unclear. Thus, this study aims to investigate the molecular events in RCT synovium and identify possible target genes and pathways as determined by RNA sequencing (RNA-Seq). The synovial tissue was biopsied from 3 patients with RCT (RCT group) and 3 patients with shoulder instability (Control group) during arthroscopic surgery. Then, differentially expressed (DE) mRNAs, long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs) were comprehensively profiled by RNA-Seq. Gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and competing endogenous RNA (ceRNA) network analysis were performed to identify the potential functions of these DE genes. 447 mRNAs, 103 lncRNAs and 15 miRNAs were identified differentially expressed. The DE mRNAs were highlighted in inflammatory pathway including up-regulated T cell costimulation, positive regulation of T cell activation, and T cell receptor signaling. Down-regulated fatty acid degradation pathway and 5′-AMP-activated protein kinase (AMPK) signaling in RCT group are also enriched. Validation assay showed that the expression of pro-inflammatory molecules including IL21R, CCR5, TNFSF11, and MMP11 was significantly increased in RCT group compared with Control group. CeRNA analysis further revealed lncRNA-miRNA-mRNA regulatory networks involving IL21R and TNFSF11 in RCT. Activated synovial inflammation is the remarkable event of RCT. Importantly, increased T cell activation and disordered fatty acid metabolism signaling might play a significant role. ceRNA networks involving IL21R and TNFSF11 identified could potentially control the progression of RCT. In conclusion, our findings could provide new evidence for the molecular mechanisms of RCT and might identify new therapeutic targets. [ABSTRACT FROM AUTHOR]

In nature, cytochrome c oxidases catalyze the 4e− oxygen reduction reaction (ORR) at the heme/Cu site, in which CuI is used to assist O2 activation. Because of the thermodynamic barrier to generate CuI, synthetic Fe‐porphyrin/Cu complexes usually show moderate electrocatalytic ORR activity. We herein report on a Co‐corrole/Co complex 1‐Co for energy‐efficient electrocatalytic ORR. By hanging a CoII ion over Co corrole, 1‐Co realizes electrocatalytic 4e− ORR with a half‐wave potential of 0.89 V versus RHE, which is outstanding among corrole‐based electrocatalysts. Notably, 1‐Co outperforms Co corrole hanged with CuII or ZnII. We revealed that the hanging CoII ion can provide an electron to improve O2 binding thermodynamically and dynamically, a function represented by the biological CuI ion of the heme/Cu site. This work is significant to present a remarkable ORR electrocatalyst and to show the vital role of a second‐sphere redox‐active metal ion in promoting O2 binding and activation. [ABSTRACT FROM AUTHOR]

In nature, cytochrome c oxidases catalyze the 4e− oxygen reduction reaction (ORR) at the heme/Cu site, in which CuI is used to assist O2 activation. Because of the thermodynamic barrier to generate CuI, synthetic Fe‐porphyrin/Cu complexes usually show moderate electrocatalytic ORR activity. We herein report on a Co‐corrole/Co complex 1‐Co for energy‐efficient electrocatalytic ORR. By hanging a CoII ion over Co corrole, 1‐Co realizes electrocatalytic 4e− ORR with a half‐wave potential of 0.89 V versus RHE, which is outstanding among corrole‐based electrocatalysts. Notably, 1‐Co outperforms Co corrole hanged with CuII or ZnII. We revealed that the hanging CoII ion can provide an electron to improve O2 binding thermodynamically and dynamically, a function represented by the biological CuI ion of the heme/Cu site. This work is significant to present a remarkable ORR electrocatalyst and to show the vital role of a second‐sphere redox‐active metal ion in promoting O2 binding and activation. [ABSTRACT FROM AUTHOR]

Jamestown Canyon virus (JCV), a negative-sense arbovirus, is increasingly common in the upper Midwest of the USA. Transmitted by a range of mosquito genera, JCV's primary amplifying host is white-tailed deer. Aedes aegypti is responsible for transmitting various positive-sense viruses globally including dengue (DENV), Zika, chikungunya, and Yellow Fever. Ae. aegypti's distribution, once confined to the tropics, is expanding, in part due to climate change. Wolbachia, an insect endosymbiont, limits the replication of co-infecting viruses inside insects. The release and spread of the symbiont into Ae. aegypti populations have been effective in reducing transmission of DENV to humans, although the mechanism of Wolbachia-mediated viral blocking is still poorly understood. Here we explored JCV infection potential in Ae. aegypti, the nature of the vector's immune response, and interactions with Wolbachia infection. We show that Ae. aegypti is highly competent for JCV, which grows to high loads and rapidly reaches the saliva after an infectious blood meal. The mosquito immune system responds with strong induction of RNAi and JAK/STAT. Neither the direct effect of viral infection nor the energetic investment in immunity appears to affect mosquito longevity. Wolbachia infection blocked JCV only in the early stages of infection. Wolbachia-induced immunity was small compared to that of JCV, suggesting innate immune priming does not likely explain blocking. We propose two models to explain why Wolbachia's blocking of negative-sense viruses like JCV may be less than that of positive-sense viruses, relating to the slowdown of host protein synthesis and the triggering of interferon-like factors like Vago. In conclusion, we highlight the risk for increased human disease with the predicted future overlap of Ae. aegypti and JCV ranges. We suggest that with moderate Wolbachia-mediated blocking and distinct biology, negative-sense viruses represent a fruitful comparator model to other viruses for understanding blocking mechanisms in mosquitoes. Author summary: Jamestown Canyon virus (JCV), a newly emerging virus in North America, can result in disease spillover from wild mammals into human populations via the bite of infected mosquitoes. We show that the mosquito Aedes aegypti, known for transmitting many viral pathogens to humans globally, and whose distribution is creeping northward in the USA toward regions where JCV is present, is likely able to transmit the virus. Wolbachia is an endosymbiotic bacterium being released in wild mosquito populations of because it limits the replication of human viruses inside the mosquito, limiting their transmission to humans. We show that Wolbachia has a limited ability to control the replication of JCV, which is likely because Wolbachia-induced antiviral response is quite weak, and unique aspects of negative-sense virus biology make them less susceptible to blocking. Our findings suggest that JCV may serve as a comparative model to positive-sense viruses like dengue in dissecting the mechanism of Wolbachia-mediated virus blocking. It also warns that shifting mosquito distributions, as expected under a changing climate, could bring JCV and Aedes mosquitoes into greater contact, potentially increasing the incidence of JCV in humans. [ABSTRACT FROM AUTHOR]

Among all the structural formations, fiber-like structure is one of the most common modalities in organisms that undertake essential functions. Alterations in spatial organization of fibrous structures can reflect information of physiological and pathological activities, which is of significance in both researches and clinical applications. Hence, the quantification of subtle changes in fiber-like structures is potentially meaningful in studying structure-function relationships, disease progression, carcinoma staging and engineered tissue remodeling. In this study, we examined a wide range of methodologies that quantify organizational and morphological features of fibrous structures, including orientation, alignment, waviness and thickness. Each method was demonstrated with specific applications. Finally, perspectives of future quantification analysis techniques were explored. [ABSTRACT FROM AUTHOR]

Wolbachia, a gram-negative endosymbiotic bacterium widespread in arthropods, is well-known for changing the reproduction of its host in ways that increase its rate of spread, but there are also costs to hosts that can reduce this. Here we investigated a novel reproductive alteration of Wolbachia wAlbB on its host Aedes aegypti, using studies on mosquito life history traits, ovarian dissection, as well as gene expression assays. We found that an extended period of the larval stage as well as the egg stage (as previously shown) can increase the proportion of Wolbachia-infected females that become infertile; an effect which was not observed in uninfected females. Infertile females had incomplete ovarian formation and also showed a higher frequency of blood feeding following a prior blood meal, indicating that they do not enter a complete gonotrophic cycle. Treatments leading to infertility also decreased the expression of genes related to reproduction, especially the vitellogenin receptor gene whose product regulates the uptake of vitellogenin (Vg) into ovaries. Our results demonstrate effects associated with the development of infertility in wAlbB-infected Ae. aegypti females with implications for Wolbachia releases. The results also have implications for the evolution of Wolbachia infections in novel hosts. Author summary: Wolbachia bacteria reduce the transmission of dengue and other arboviruses transmitted by their mosquito hosts once they have invaded host populations. This invasion process is being undertaken in Aedes aegypti mosquito populations throughout the world but can be slowed by deleterious fitness costs that the Wolbachia bacteria have on their mosquito hosts. Here we investigate in detail a recently identified cost where one of the Wolbachia strains being used in invasions causes infertility in females when the females develop from eggs that have been stored for a period. We show that slowed larval development (through food reduction) can cause the same phenomenon and that the emerged females lack functional ovaries. These infertile females also take blood meals more often. The results have implications for the successful invasion of Wolbachia under ecological circumstances where the mosquito eggs have to persist in the absence of water for a period and where larval food is limiting. [ABSTRACT FROM AUTHOR]

The plethora of pathways leading to health problems of later life has made the causal assessment of widowhood on the health of older adults difficult. This research aimed to assess the short‐term impact of widowhood on the objective health of older adults and to the moderating role of community‐based care (CBC) in improving the health outcomes of older adults. In this study, the activities of daily living (ADLs) and number of hospitalisations of older adults were measured, and PSM‐DID models were conducted. Widowhood had a significant negative impact on the objective health of older adults. Widowed adults had higher ADL scores (B = 0.569, 95 percent CI: 0.295 to 0.844) and more hospitalisations (B = 2.551, 95 percent CI: 1.189 to 3.914) than nonwidowed adults. Meanwhile, CBC in urban areas can significantly reduce ADL scores (B = −0.154, SE = 0.082) and the number of hospitalisations (B = −1.402, SE = 0.348) in older adults, whereas CBC in rural areas can only significantly reduce ADL scores (B = −0.197, SE = 0.087). Taken together, there is an urgent need to focus on the health of widowed and older adults and to provide CBC in both urban and rural areas equally. [ABSTRACT FROM AUTHOR]

To detect bull’s-eye anomalies in low-frequency seismic inversion models, the study proposed an advanced method using an optimized you only look once version 7 (YOLOv7) model. This model is enhanced by integrating advanced modules, including the bidirectional feature pyramid network (BiFPN), weighted intersection-over-union (wise-IoU), efficient channel attention (ECA), and atrous spatial pyramid pooling (ASPP). BiFPN facilitates robust feature extraction by enabling bidirectional information flow across network scales, which enhances the ability of the model to capture complex patterns in seismic inversion models. Wise-IoU improves the precision and fineness of reservoir feature localization through its weighted approach to IoU. Meanwhile, ECA optimizes interactions between channels, which promotes effective information exchange and enhances the overall response of the model to subtle inversion details. Lastly, the ASPP module strategically addresses spatial dependencies at multiple scales, which further enhances the ability of the model to identify complex reservoir structures. By synergistically integrating these advanced modules, the proposed model not only demonstrates superior performance in detecting bull’s-eye anomalies but also marks a pioneering step in utilizing cutting-edge deep learning technologies to enhance the accuracy and reliability of seismic reservoir prediction in oil and gas exploration. The results meet scientific literature standards and provide new perspectives on methodology, which makes significant contributions to ongoing efforts to refine accurate and efficient prediction models for oil and gas exploration. [ABSTRACT FROM AUTHOR]

WOX11/12 is a homeobox gene of WOX11 and WOX12 in Arabidopsis that plays important roles in crown root development and growth. It has been reported that WOX11/12 participates in adventitious root (AR) formation and different abiotic stress responses, but the downstream regulatory network of WOX11/12 in poplar remains to be further investigated. In this study, we found that PagWOX11/12a is strongly induced by PEG-simulated drought stress. PagWOX11/12a -overexpressing poplar plantlets showed lower oxidative damage levels, greater antioxidant enzyme activities and reactive oxygen species (ROS) scavenging capacity than non-transgenic poplar plants, whereas PagWOX11/12a dominant repression weakened root biomass accumulation and drought tolerance in poplar. RNA-seq analysis revealed that several differentially expressed genes (DEGs) regulated by PagWOX11/12a are involved in redox metabolism and drought stress response. We used RT-qPCR and yeast one-hybrid (Y1H) assays to validate the downstream target genes of PagWOX11/12a. These results provide new insights into the biological function and molecular regulatory mechanism of WOX11/12 in the abiotic resistance processes of poplar. • PagWOX11/12a is induced by PEG-simulated drought stress. • Overexpression of PagWOX11/12a enhances drought tolerance by regulating ROS levels and antioxidant enzyme activity. • PagWOX11/12a can bind to the PagBURP24 and PagbHLH63 promoters and activate their expression. [ABSTRACT FROM AUTHOR]

The energy band structure of PEDOT:PSS films is regulated via secondary doping, the tribovoltaic effect is notably enhanced, and thus outputs and robustness of the polymeric tribovoltaic generator is significantly boosted in contact-separation or sliding mode. [Display omitted] • A polymeric tribovoltaic generator achieves boosted outputs and robustness through energy band engineering strategy. • The transferred charge quantity per motion cycle reaches 150.48 mC m−2 and 225.73 mC m−2 in contact-separation and sliding mode, respectively. • The tribovoltaic device achieves exceptional durability over 100,000 contact-separation cycles. • Exceptional humidity resistance is demonstrated. The semiconductor-based tribovoltaic nanogenerator (TVNG) garners distinctive characteristics of direct current output at low internal impedance, rendering it great potentials for self-powered electronics. We present a polymeric TVNG for achieving enhanced electrical outputs and robustness through secondary doping strategy. By utilizing the dimethyl sulfoxide (DMSO) as a dopant, the transport properties of semiconducting poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) can be modulated. We then demonstrate that the tribovoltaic outputs can be significantly enhanced due to the improved conductivity of the PEDOT:PSS and the enlarged Schottky barrier at the dynamic metal–semiconductor interfaces. The quantity of the transferred charge per motion cycle can reach 150.48 mC m−2 in contact-separation mode and 225.73 mC m−2 in sliding mode. Meantime, the dopant improves the flexibility of the PEDOT:PSS and hence the mechanical robustness of TVNG, allowing stable outputs for ∼ 100,000 contact-separation operations cycles or ∼ 36,000 bending cycles. Furthermore, the device also demonstrates exceptional humidity resistance, but confirms a coupling of tribovoltaic effect and electrochemical effect in high-humidity conditions (relative humidity over 90%). Therefore, our findings provide insightful strategies for future optimization of practical tribovoltaic devices. [ABSTRACT FROM AUTHOR]

• The stability, symmetry and interfacial wave of liquid film are analyzed. • Downstream void fraction PDFs for slug flow are bimodal with swirler 3 and 5 turns. • Reveal the liquid-carrying mechanism by disturbance waves and momentum transfer. • Two predictive models for swirler pressure loss are proposed. The behaviors of gas-liquid swirling flow under various swirler turns, neglected in previous studies, are essential for swirling flow applications. The role of swirler turns (1, 3, 5) in swirling flow characteristics was systematically investigated in a horizontal pipeline with an inner diameter of 32 mm. The temporal stability and circumferential symmetry of swirling liquid film become better with increasing swirler turns. The periodicity of the swirling liquid film interfacial wave induced by slug flow increases as the swirler turns decrease, while the main wave frequency decreases. Interestingly, for the original slug flow, the downstream void fraction probability density function curves are bimodal with 3 and 5 turns, while it is single-peaked at the swirler with 1 turn. The effectiveness of swirler with 1 turn, 3 turns, and 5 turns in promoting carrying liquid was 100 %, 82.08 %, and 89.22 %, respectively. The mechanism of liquid-carrying was explained in terms of perturbation waves and momentum transfer in the gas-liquid interface. Based on the homogeneous flow model and separated flow model, two predictive models for swirler pressure loss were proposed with maximum errors of 14.67 % and 17.86 %, respectively. [Display omitted] [ABSTRACT FROM AUTHOR]

With the progression of diseases, modified cell–matrix interactions have major effects not only upon key cellular functions but also upon the structure of extracellular matrix and vasculature, which are two of the most prevalent fiber‐like structures in biological tissues. Unfortunately, quantitative approaches to assessing these structural changes are lacking. Herein, a multiparametric imaging system is established to resolve subtle organizational changes of collagen fibers and vasculature in disease progression. The pixel‐wise, automated waviness (paWav) is developed as a novel biomarker, and a multimodal analysis system combining paWav with orientation and alignment assessments is constructed. Aggregation‐induced emission luminogens (AIEgens) with second near‐infrared excitation or emission are developed for in vivo deep‐penetration vasculature imaging. The organization remodeling of cortical blood vessels in stroke in marmosets is quantitatively characterized using biologically excretable AIE dots that highlight the clinical translation potential, and a distance dependence law in vessel morphological remodeling is identified. Finally, the multiparametric analysis relying completely on collagen fiber signatures successfully differentiates cancerous from normal pancreatic tissues using a predictive classification approach. Collectively, the combined use of these structural changes in fibrillar tissue components may enable a better understanding of cell–matrix interactions in pathogenesis and identification of new potential treatment targets. [ABSTRACT FROM AUTHOR]

A new compound, {[Co(TPA)(PYIM)2(H2O)2](MI)4}n(1)(H2TPA = terephthalic acid, PYIM = 2-(3-pyridine) benzimidazole, MI = 2-lmidazolidone) has been urothermal synthesized and structurally characterized by elemental analysis, IR Spectra, the Powder Diffraction and single-crystal X-ray diffraction. Single-crystal X-ray diffraction analysis reveals that the (1 D)+(2D hydrogen bonds) pillar the compound 1 into an open 3 D supramolecular framework with a pore along the b axis (approximate dimensions 4.5 × 15 Å2), which is occupied by free MI molecules. In addition, the catalytic-degradation capacity of compound 1 for methylene blue (MB) was investigated. Supplemental data for this article can be accessed online at 10.1080/24701556.2021.1916760 [ABSTRACT FROM AUTHOR]

Introduction: Implementing integrated care for the aged population has been regarded as a mechanism to achieve healthy ageing. However, evidence from undeveloped nations has been scant. This study aims to explore the integrated care experience in Anhui and Fujian Province of China based on the Rainbow Model of Integrated Care (RMIC). Methods: The qualitative study was conducted in Anhui (in the middle area) and Fujian Province (in the eastern area) between May and September in 2018. The interviewees included twenty-eight policy makers working at departments of health and civil affairs at different levels and seventeen heads of medical and elderly care institutions. Results: The preliminary progress of integrated care in the sample cities of two provinces are mainly shown at solid policy basis by multiple key government agencies and political commitment achieved (system integration); preliminary coordination mechanism established between medical and elderly care institutions (organizational integration); consolidation of multi-disciplinary collaboration (professional integration); and reinforced role of family doctor teams for community-home dwelling elderly (service integration). Main challenges are also identified at insufficient inter-agency coordination, weak service capacity, lack of sustainable funding schemes, low level of information integration, and shortage of professional supply. Conclusion: Our findings provide a feasible path for other countries to strengthen integrated care for the aged population, particularly for those confronting rapid population ageing but with fragmented health care and elderly care systems. [ABSTRACT FROM AUTHOR]

Oral cancer is among the top 10 causes of death due to cancer worldwide. The prognosis for oral cancer patients is not good, with a 5-year survival rate of only 50%. Earlier and more precise classification will help clinicians make a diagnosis and patients survive. With the advancement of technology, computer-aided detection methods are used to help clinicians form therapy strategies. Gray-level co-occurrence matrix (GLCM) feature extraction of images describing the spatial distribution of gray levels is widely used in medical imaging analysis. Scanned laser pico projector (SLPP) has advantages such as high intensity, directivity, coherence, and mono-color with low bandwidth. In this study, GLCM feature extraction and SLPP reflex images were combined to make a small, non-staining, noninvasive classification system. According to the various image characteristics in oral carcinogenesis, SLPP reflex images better define the borders and three-dimensional structures and provide effective GLCM features such as contrast, energy, and homogeneity to classify carcinogenesis in dysplastic oral keratinocyte (DOK) and normal oral keratinocyte (NOK) cells. Moreover, it also reliably classifies highly metastatic (HSC-3) and tongue cancer (CAL-27) cells. A promising computer-aided classification system for oral cancer was developed to build a reliable intraoral examination system for in situ computer-aided diagnosis in normal clinics. [ABSTRACT FROM AUTHOR]

Boron (B) doping plays a critical role in adjusting the electronic properties of carbon materials. In this work, B-doped porous graphene (B-PG) was successfully prepared by a simple strategy and used as an advanced electrode material for the detection of nitrite (NO- 2) in food. The scanning electron microscopy (SEM), high resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were employed to characterize this B-PG. Due to the ideal doping of boron atoms, the material has good conductivity and exhibits excellent electrochemical catalytic performance. NO- 2 was used as the representative analytes to demonstrate the sensing performance of B-PG. It is found that the B-PG modified GCE exhibited a linear response over the concentration range from 3 μM – 3 mM and 3 mM – 15 mM, with a detection limit of 1.1 μM. The designed electrochemical sensor has good analytical performance, such as high sensitivity, good reproducibility and acceptable accuracy, and can be successfully applied to the accurate and precise detection of residual NO- 2 in food. • A novel nanomaterial of porous graphene doped with B atoms (B-PG) was prepared. • B-PG exhibits excellent electrocatalytic activity for nitrite. • The electrochemical sensor has good stability and anti-interference performance. • It can be successfully applied to the detection of residual detect nitrite in food. [ABSTRACT FROM AUTHOR]

NAC transcription factors play a significant role in regulating plant responses to biological processes and environmental stresses. Our previous study revealed 21 ThNAC proteins, and ThNAC13 is a nuclear protein that responds to saline stress in Tamarix hispida. To determine whether ThNAC13 regulates downstream genes, RNA sequencing (RNA-seq) and DNA affinity purification sequencing (DAP-seq) were used to identify the binding sites of ThNAC13 at the whole-genome level. In RNAi-silenced ThNAC13 transgenic Tamarix , a total of 4 downregulated differentially expressed genes (DEGs) and 114 peaks strongly associated with four different motifs were identified compared with those in empty vector transgenic Tamarix under salt stress. The c48149.graph_c0 gene contains the key domain of the phloem protein 2 (PP2) protein and is a candidate gene downstream of ThNAC13. Yeast one-hybrid (Y1H), chromatin immunoprecipitation (ChIP) and dual-luciferase reporter (LUC) assays were used to identify ThNAC13 as an upstream regulator of ThPP2. Transgenic Tamarix plants in which ThPP2 was transiently expressed or silenced via RNAi were used for functional gain and loss experiments. The ThPP2- overexpressing plants exhibited decreased hydrogen peroxide (H 2 O 2), superoxide (O 2 •−), and electrolyte leakage (EL) and malondialdehyde (MDA) levels and increased superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) activity. In contrast, transient RNAi-mediated silencing of ThPP2 in Tamarix had the opposite effect. ThNAC13 binds to the promoter region of the ThPP2 gene and reduces the reactive oxygen species (ROS) accumulation and enhances antioxidant enzyme activity, positively regulating salt stress tolerance in Tamarix. • 4 down-regulated DEGs and 4 different motifs were identified in RNAi-silenced ThNAC13 compare with empty vector transgenic Tamarix under salt stress. • The phloem protein 2 (PP2) protein as a downstream gene by ThNAC13 TFs. • Overexpression of ThPP2 Tamarix decreased the contents of H 2 O 2 , O 2 •−, EL and MDA; induced the activities of SOD, POD and CAT. • In contrast, transiently RNAi-silenced ThPP2 Tamarix showed the opposite result. • ThNAC13 binds to ThPP2 gene through reduces the ROS accumulation and enhances antioxidant enzyme activity to improve salt stress tolerance. [ABSTRACT FROM AUTHOR]

Electro‐optic (EO) modulation allows the conversion of electrical signals to optical pulses and is widely employed in telecommunications and chip‐to‐chip interconnects. Recently, hybrid organic–inorganic perovskites (HOIPs) have been explored as candidates for EO modulators. To improve the EO performance, it is envisioned that halide doping will lower the symmetry of the crystal, enhancing spontaneous polarization. However, mixed halide perovskites are often associated with ion migration, which may impact their EO properties. Thus, the influence of ion migration on the EO efficiency is investigated using Br‐doped Dion–Jacobson quasi‐2D HOIPs, (4AMP)(MA)Pb2(Brx/I1−x)7 (4AMP = 4‐(aminomethyl)piperidinium, MA = methylammonium). While density functional theory predicts a greater spontaneous polarization for the Br‐doped sample, it is found that experimental results are affected by ion migration. The EO coefficient of the Br/I mixed sample is 95 pm V−1 at 1 kHz (≈50× higher than the undoped sample), but the response falls off rapidly with frequency. This frequency dependence is correlated with impedance spectroscopy, showing that the large EO signal results from ion migration. This study shows that ion migration impacts the EO analysis of mixed halide perovskites and must be considered in future EO studies. [ABSTRACT FROM AUTHOR]

Background: Wolbachia wMel is the most commonly used strain in rear and release strategies for Aedes aegypti mosquitoes that aim to inhibit the transmission of arboviruses such as dengue, Zika, Chikungunya and yellow fever. However, the long-term establishment of wMel in natural Ae. aegypti populations raises concerns that interactions between Wolbachia wMel and Ae. aegypti may lead to changes in the host genome, which could affect useful attributes of Wolbachia that allow it to invade and suppress disease transmission. Results: We applied an evolve-and-resequence approach to study genome-wide genetic changes in Ae. aegypti from the Cairns region, Australia, where Wolbachia wMel was first introduced more than 10 years ago. Mosquito samples were collected at three different time points in Gordonvale, Australia, covering the phase before (2010) and after (2013 and 2018) Wolbachia releases. An additional three locations where Wolbachia replacement happened at different times across the last decade were also sampled in 2018. We found that the genomes of mosquito populations mostly remained stable after Wolbachia release, with population differences tending to reflect the geographic location of the populations rather than Wolbachia infection status. However, outlier analysis suggests that Wolbachia may have had an influence on some genes related to immune response, development, recognition and behavior. Conclusions: Ae. aegypti populations remained geographically distinct after Wolbachia wMel releases in North Australia despite their Wolbachia infection status. At some specific genomic loci, we found signs of selection associated with Wolbachia, suggesting potential evolutionary impacts can happen in the future and further monitoring is warranted. [ABSTRACT FROM AUTHOR]

Soymilk is a popular beverage in many countries owing to its nutrition and health effects. To increase household consumption of soymilk, instant soybeans were developed by freezing and subsequent drying pretreatment, which overcome the time‐consuming need of soaking during soymilk preparation for home making. However, compared with the traditional soymilk making, the nutritional quality and functional properties of this soymilk made from the soybean by direct grinding in water without soaking are not clear yet. Soymilk made from untreated soybeans, soaked soybeans, and soaking, freezing, and air‐drying soybeans (FADTS) were compared on their properties including nutritional components, in vitro protein digestibility, and functional components. It was found that FADTS was the best at extracting lipid and Ca, good at extracting of protein, carbohydrate, oligosaccharides, Fe, phytic acids, and tannins, and in producing soymilks with highest in vitro protein digestibility. The soluble protein and protein digestibility of FADTS (4 day) increased significantly from 44.4% and 78.5% of control to 56.2% and 85.0%, respectively. Soymilk from 4 days FADTS contained similar protein content and higher Fe content (4.40 mg/kg) compared to soaked sample (3.82 mg/kg). The results revealed that FADTS performed better at producing soymilk than untreated and soaked soybeans. [ABSTRACT FROM AUTHOR]

Detection of the Wolbachia endosymbiont in Aedes aegypti mosquitoes through real-time polymerase chain reaction assays is widely used during and after Wolbachia releases in dengue reduction trials involving the wMel and wAlbB strains. Although several different primer pairs have been applied in current successful Wolbachia releases, they cannot be used in a single assay to distinguish between these strains. Here, we developed a new diagnostic primer pair, wMwA, which can detect the wMel or wAlbB infection in the same assay. We also tested current Wolbachia primers and show that there is variation in their performance when they are used to assess the relative density of Wolbachia. The new wMwA primers provide an accurate and efficient estimate of the presence and density of both Wolbachia infections, with practical implications for Wolbachia estimates in field collected Ae. aegypti where Wolbachia releases have taken place. [ABSTRACT FROM AUTHOR]

Novel properties and applications of multilayered nanowires (MNWs) urge researchers to understand their mechanical behaviors comprehensively. Using the molecular dynamic simulation, tensile behaviors of Ti/Ni MNWs are investigated under a series of layer thickness values (1.31, 2.34, and 7.17 nm) and strain rates (). The results demonstrate that deformation mechanisms of isopachous Ti/Ni MNWs are determined by the layer thickness and strain rate. Four distinct strain rate regions in the tensile process can be discovered, which are small, intermediate, critical, and large strain rate regions. As the strain rate increases, the initial plastic behaviors transform from interface shear (the shortest sample) and grain reorientation (the longest sample) in small strain rate region to amorphization of crystalline structures (all samples) in large strain rate region. Microstructure evolutions reveal that the disparate tensile behaviors are ascribed to the atomic fractions of different structures in small strain rate region, and only related to collapse of crystalline atoms in high strain rate region. A layer thickness-strain rate-dependent mechanism diagram is given to illustrate the couple effect on the plastic deformation mechanisms of the isopachous nanowires. The results also indicate that the modulation ratio significantly affects the tensile properties of unequal Ti/Ni MNWs, but barely affect the plastic deformation mechanisms of the materials. The observations from this work will promote theoretical researches and practical applications of Ti/Ni MNWs. [ABSTRACT FROM AUTHOR]

As a result of the Every Student Succeeds Act (ESSA), schools and districts are encouraged to implement school-wide initiatives to improve outcomes for all students. In accordance with the ESSA, this research study investigated the relationship between school improvement planning and the implementation of school-wide interventions. The study examined survey and extant data from five high schools in a Midwestern state to analyze academic and behavior-related school-wide efforts and their relationship to school improvement. The data showed a statistically significant relationship between school improvement planning and the state's school improvement report card of student performance (Kendall Rank-Order Coefficient, p =.025). These findings suggest that schools might consider integrating their school-wide efforts into school improvement planning. [ABSTRACT FROM AUTHOR]

Background: One of the most noticeable integrated care-related policies in China is the growth and proliferation of County-level Integrated Health Organizations (CIHOs), which take over a set of primary healthcare institutions to form an integrated delivery network in order to achieve an ordered hierarchical delivery system by strengthening primary care. Objectives: This paper presents emerging findings from an ongoing evaluation of the early impacts of the demonstrator site, Deqing CIHO, in Zhejiang Province, in order to examine the extent to which the implementation has achieved its core objectives: (1) establishing the hierarchical referral system, (2) capacity building of primary healthcare providers, and (3) reducing the costs. Design: This case study was conducted to determine institutional and managerial processes. Settings: Data were collected and analyzed at the CIHO and county level. A structured questionnaire was used for data collection. Primary and secondary outcome measures: Indicators were selected from the existing database of the county health system and arranged into three segments to assess (1) service utilization among each level of care; (2) capacity-building progress for primary care centers, (3) cost-related indicators for both levels of care. Results: Service utilization data show that one year after CIHO implementation, the proportion of patients who chose to get inpatient care outside of the county decreased from 27.3% to 24.5%. Hospital admissions were retrieved from outside the county, while service volume slightly shifted from hospitals to primary care sites. Capacitybuilding indicators for township health centers show that 6 out of 12 items showed better performance compared to the national average growth rate, and a moderated growth rate appeared in terms of per capita cost. Conclusion: Progress evaluation results from Deqing CIHO indicated some positive effects on three main outcomes, which reveal the potential of CIHOs in not only strengthening primary care but also controlling cost as a result of early implementation. Further emphases of evaluation are required to determine the impacts on the quality and experience of care that are estimated using claim-based data at the individual level. [ABSTRACT FROM AUTHOR]

Background: The impact of self‐expandable metal stent (SEMS) for malignant right colonic obstruction remains undefined. The aim of this study was to compare short‐term postoperative and long‐term oncologic outcomes of colonic stenting as a bridge to surgery (SBTS) and urgent colectomy for patients with malignant right‐sided obstruction. Methods: A total of 98 consecutive patients who underwent SEMS placement during the period 2004–2015 from three hospitals were included. For comparative analyses, patients were matched (1:2) with 196 patients treated with emergency colectomy from our prospective database. Results: The two groups were comparable in terms of demographics and tumor characteristics. The proportion of patients who underwent laparoscopic colectomy was higher in SBTS group than urgent colectomy group (75.5% vs. 37.2%; p < 0.001). Patients treated with SBTS were less likely to have a temporary stoma constructed (3.1% vs. 10.7%; p = 0.024). SBTS was associated with significantly less median estimated blood loss (90 vs. 100 ml; p = 0.029), shorter length of hospital stay (11 vs. 12 days; p < 0.001), lower overall postoperative complication rate (18.4% vs. 31.3%; p = 0.018), and wound‐related complication rate (5.1% vs. 14.3%; p = 0.019) compared with urgent surgery. Reoperation rate, 30‐day mortality, and lymph nodes harvested were not significantly different between two groups. Disease‐free survival rate and overall survival rate were similar between the two groups. Conclusions: SEMS insertion is safe and feasible for treating malignant right‐sided obstruction. SBTS is associated with better short‐term outcomes and equivalent long‐term oncologic results compared with urgent colectomy. [ABSTRACT FROM AUTHOR]

In this study, an investigation was conducted into the effects of different pH values of citric acid solutions combined with ultrasound irradiation on the amino acids of the apricot kernels during debitterizing. The concentrations and varieties of amino acids in the samples were determined using the automatic amino acid analyzer. In addition, the amino acid reference model proposed by WHO/FAO was adopted as the evaluation criteria, and the ratio of essential amino acids in debitterized samples was compared to assess the effect of ultrasonic debitterizing of different pH solutions on the nutritional value carried by apricot kernels amino acids. Finally, with the amino acid content as a parameter, principal component analysis (PCA) and cluster analysis (HCA) were carried out to thoroughly evaluate the nutritional value of amino acids contained in the debitterized apricot kernels. The results indicate that the citric acid solution with a pH value of 5 could be taken as the optimal ultrasonic solution to remove the bitterness of apricot kernels. Specifically, the total amino acid content and the nutritional value of the apricot kernel are high after debitterizing under the condition, which could shorten the debitterizing of apricot kernels and provide highly nutritious amino acids. Novelty impact statement: This work can maintain the properties of apricot kernels amino acids to a better extent based on rapid debitterizing. Ultrasound coupled with the citric acid solution as a new method was used to debitterizing apricot kernels. Finally, the debitterizing conditions could be optimized to obtain apricot kernels amino acids of good quality. [ABSTRACT FROM AUTHOR]

In this work, we isolated and characterized fusapyrone A (1), a new γ-pyrone derivative, along with six previously described compounds from the rice fermentation of Fusarium sp. CPCC 401218, a fungus collected from the desert. The structure of 1 was characterized using various spectroscopic analyses, such as MS, IR, 1D, and 2D NMR. The absolute configuration of 1 was determined through the use of 13C NMR chemical shifts, electronic circular dichroism (ECD) and optical rotation (OR) calculations. Compound 1 was found to have weak antiproliferative activity for Hela cells, with an IC50 of 50.6 μM. [ABSTRACT FROM AUTHOR]

In situ observation of precipitation or phase separation induced by solvent addition is important in studying its dynamics. Combined with optical and fluorescence microscopy, microfluidic devices have been leveraged in studying the phase separation in various materials including biominerals, nanoparticles, and inorganic crystals. However, strong scattering from the subphases in the mixture is problematic for in situ study of phase separation with high temporal and spatial resolution. In this work, we present a quasi-2D microfluidic device combined with total internal reflection microscopy as an approach for in situ observation of phase separation. The quasi-2D microfluidic device comprises of a shallow main channel and a deep side channel. Mixing between a solution in the main channel (solution A) and another solution (solution B) in the side channel is predominantly driven by diffusion due to high fluid resistance from the shallow height of the main channel, which is confirmed using fluorescence microscopy. Moreover, relying on diffusive mixing, we can control the composition of the mixture in the main channel by tuning the composition of solution B. We demonstrate the application of our method for in situ observation of asphaltene precipitation and β -alanine crystallization. [ABSTRACT FROM AUTHOR]

Objectives: Although axitinib has achieved a preferable response rate for advanced renal cell carcinoma (RCC), patient survival remains unsatisfactory. In this study, we evaluated the efficacy and safety of a combination treatment of axitinib and a low dose of pembrolizumab‐activated autologous dendritic cells–co‐cultured cytokine‐induced killer cells in patients with advanced RCC. Methods: All adult patients, including treatment‐naive or pretreated with VEGF‐targeted agents, were enrolled from May 2016 to March 2019. Patients received axitinib 5 mg twice daily and pembrolizumab‐activated dendritic cells–co‐cultured cytokine‐induced killer cells intravenously weekly for the first four cycles, every 2 weeks for the next four cycles, and every month thereafter. Results: The 43 patients (22 untreated and 21 previously treated) showed a median progression‐free survival (mPFS) of 14.7 months (95% CI, 11.16–18.30). mPFS in treatment‐naive patients was 18.2 months, as compared with 14.4 months in pretreated patients (log‐rank P‐value = 0.07). Overall response rates were 25.6% (95% CI, 13.5–41.2%). Grade 3 or higher adverse events occurred in 5% of patients included hypertension (11.6%) and palmar‐plantar erythrodysesthesia (7.0%). Peripheral blood lymphocyte immunophenotype and serum cytokine profile analyses demonstrated increased antitumor immunity after combination treatment particularly in patients with a long‐term survival benefit, while those with a minimal survival benefit demonstrated an elevated proportion of peripheral CD8+TIM3+ T cells and lower serum‐level immunostimulatory cytokine profile. Conclusions: The combination therapy was active and well tolerated for treatment of advanced RCC, either as first‐ or second‐line treatment following other targeted agents. Changes in immunophenotype and serum cytokine profile may be used as prognostic biomarkers. [ABSTRACT FROM AUTHOR]

The endosymbiotic bacterium Wolbachia shows viral blocking in its mosquito host, leading to its use in arboviral disease control. Releases with Wolbachia strains wMel and wAlbB infecting Aedes aegypti have taken place in several countries. Mosquito egg survival is a key factor influencing population persistence and this trait is also important when eggs are stored prior to releases. We therefore tested the viability of mosquitoes derived from Wolbachia wMel and wAlbB-infected as well as uninfected eggs after long-term storage under diurnal temperature cycles of 11–19°C and 22–30°C. Eggs stored at 11–19°C had higher hatch proportions than those stored at 22–30°C. Adult Wolbachia density declined when they emerged from eggs stored for longer, which was associated with incomplete cytoplasmic incompatibility (CI) when wMel-infected males were crossed with uninfected females. Females from stored eggs at both temperatures continued to show perfect maternal transmission of Wolbachia, but storage reduced the fecundity of both wMel and wAlbB-infected females relative to uninfected mosquitoes. Furthermore, we found a very strong negative impact of the wAlbB infection on the fertility of females stored at 22–30°C, with almost 80% of females hatching after 11 weeks of storage being infertile. Our findings provide guidance for storing Wolbachia-infected A. aegypti eggs to ensure high fitness adult mosquitoes for release. Importantly, they also highlight the likely impact of egg quiescence on the population dynamics of Wolbachia-infected populations in the field, and the potential for Wolbachia to suppress mosquito populations through cumulative fitness costs across warm and dry periods, with expected effects on dengue transmission. Author summary: The endosymbiont bacterium, Wolbachia, has been successfully established in natural Aedes aegypti populations to help suppress the transmission of arboviral diseases such as dengue. The fertility of infected mosquitoes experiencing a quiescent egg stage will influence the efficiency of mosquito releases when mass-reared eggs are stored and may also influence invasion. We tested stored eggs with the wMel or wAlbB infections and found that females derived from eggs stored in a warm environment had reduced fecundity. We also discovered a novel and strong fertility cost on wAlbB-infected A. aegypti, in that a high proportion of females became infertile even though they mated successfully, which was determined by the period when mosquito eggs were quiescent. This effect across life stages was not evident when eggs were stored under cooler conditions and represents the first time that Wolbachia was found to induce female infertility independent of cytoplasmic incompatibility, pointing to a likely additional phenotypic effect of Wolbachia affecting dengue transmission. [ABSTRACT FROM AUTHOR]

Background: Paeonia lactiflora 'Hangshao' is widely cultivated in China as a traditional Chinese medicine 'Radix Paeoniae Alba'. Due to the abundant unsaturated fatty acids in its seed, it can also be regarded as a new oilseed plant. However, the process of the biosynthesis of unsaturated fatty acids in it has remained unknown. Therefore, transcriptome analysis is helpful to better understand the underlying molecular mechanisms. Results: Five main fatty acids were detected, including stearic acid, palmitic acid, oleic acid, linoleic acid and α-linolenic acid, and their absolute contents first increased and then decreased during seed development. A total of 150,156 unigenes were obtained by transcriptome sequencing. There were 15,005 unigenes annotated in the seven functional databases, including NR, NT, GO, KOG, KEGG, Swiss-Prot and InterPro. Based on the KEGG database, 1766 unigenes were annotated in the lipid metabolism. There were 4635, 12,304, and 18,291 DEGs in Group I (60 vs 30 DAF), Group II (90 vs 60 DAF) and Group III (90 vs 30 DAF), respectively. A total of 1480 DEGs were detected in the intersection of the three groups. In 14 KEGG pathways of lipid metabolism, 503 DEGs were found, belonging to 111 enzymes. We screened out 123 DEGs involved in fatty acid biosynthesis (39 DEGs), fatty acid elongation (33 DEGs), biosynthesis of unsaturated fatty acid (24 DEGs), TAG assembly (17 DEGs) and lipid storage (10 DEGs). Furthermore, qRT-PCR was used to analyze the expression patterns of 16 genes, including BBCP, BC, MCAT, KASIII, KASII, FATA, FATB, KCR, SAD, FAD2, FAD3, FAD7, GPAT, DGAT, OLE and CLO, most of which showed the highest expression at 45 DAF, except for DGAT, OLE and CLO, which showed the highest expression at 75 DAF. Conclusions: We predicted that MCAT, KASIII, FATA, SAD, FAD2, FAD3, DGAT and OLE were the key genes in the unsaturated fatty acid biosynthesis and oil accumulation in herbaceous peony seed. This study provides the first comprehensive genomic resources characterizing herbaceous peony seed gene expression at the transcriptional level. These data lay the foundation for elucidating the molecular mechanisms of fatty acid biosynthesis and oil accumulation for herbaceous peony. [ABSTRACT FROM AUTHOR]

A new metal-organic framework, {[Tb(O-IDC)(O-HIDC)] (H2O)}n(1), (O-H3IDC = 2-(pyridine-N-oxide-2-yl)-1H-imidazole-4,5-dicarboxylic acid) has been constructed through hydrothermal reaction using 2-(pyridine-2-yl)-1H-imidazole-4,5-dicarboxylate(H2IDC) and Tb(NO3)3•6H2O. During the reaction, O-H2IDC resulted from the in situ oxidation reaction of H2IDC. The compound 1 has been characterized by elemental analysis, IR spectra, the Powder Diffraction and single-crystal X-ray diffraction. Compound 1 crystallizes in monoclinic space group P21/c with a = 15.116(3), b = 10.641(2), c = 13.398(3) Å, β = 92.057(4) °, V = 2153.8(8) Å3, Dc = 2.073 g/cm3, Mr = 672.28, F(000) = 1312, Z = 4, R = 0.0373 and wR = 0.0964. Compound 1 displays an infinite 1 D chain structure. Moreover, through intermolecular hydrogen bonds, these 1 D chains extend into a 3 D supramolecular framework. Furthermore, the solid-state luminescent properties have also been investigated. (CCDC 1856803) [ABSTRACT FROM AUTHOR]

• Our study provides valuable insights into the anticancer activity of novel carbazoyl hydrazine derivatives as Pim-1 inhibitors in liver cancer cells. • Molecular docking studies were performed to evaluate the putative bonding mode of the synthesized compounds (4a-4 s). • Lead compound 4r demonstrates promising potential for further exploration and development in future studies for liver cancer treatment. In this study, we investigated the anticancer activity of novel carbazoyl hydrazine derivatives as inhibitors of Proviral Integration site for Moloney murine leukemia virus kinase 1 (Pim-1) in liver cancer cells in vitro. The obtained compounds were characterized using 1H NMR, 13C NMR, HRMS, and FTIR. Through computer-assisted screening, antitumor activity testing, and Pim-1 inhibitory activity testing, most of the compounds exhibited significant inhibitory activity against liver cancer cell lines. Among them, compound N'-(2-(9H-carbazol-9-yl)acetyl)-4-fluorobenzohydrazide (4r) demonstrated a remarkable anticancer effect by inducing G2/M phase cell cycle arrest and apoptosis. It was identified as a highly efficient lead compound in our screening process. Overall, our study provides valuable insights into the anticancer activity of novel carbazoyl hydrazine derivatives as Pim-1 inhibitors in liver cancer cells. The identified lead compound 4r demonstrates promising potential for further exploration and development in future studies for liver cancer treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

The potato/tomato psyllid Bactericera cockerelli causes serious damage to several solanaceous crops by direct feeding and vectoring Candidatus Liberibacter solanacearum, a bacterial pathogen. Electron beam (eBeam) irradiation is an environmentally friendly, chemical‐free alternative method that is increasing in use for disinfestation of insect pests. We hypothesize that this irradiation technology will have detrimental effects on potato psyllid and thus impede its disease vectoring. To this end, we explored the effects of eBeam treatment ranging from 50 to 500 Gy on survival, development and reproduction of this pest. Impact on psyllids was apparently dose‐dependent. When irradiated at 350 Gy, eggs could not hatch, 1st instar nymphs failed to emerge, and although a small portion of irradiated 5th instar nymphs survived, the emerged adults were mostly deformed. Abnormality in eclosed adults suggests harmful effects of eBeam on metamorphosis. Reproduction was seriously impaired when female psyllids were exposed to eBeam at the 5th instar nymphal or young adult stage, presumably due to inability to form oocytes. In addition, reciprocal crosses between irradiated and untreated psyllids indicated that female psyllids were more radiosensitive than males to eBeam. Taken together, these findings indicate that eBeam negatively impacted potato psyllid development and reproduction, which would inevitably compromise its disease transmission capacity. A dose of 350 Gy can be considered as a reference dose for effective control of potato psyllids. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the relationships between cognitive emotion regulation (CER) strategies, resilience, and insomnia and the underlying mechanism that explains the relationships. Six hundred and fifty-three middle-aged and old people recruited from community service centers in Henan province completed questionnaires related to CER strategies, resilience, and insomnia. Results showed refocus on planning and positive reappraisal negatively predicted insomnia, and catastrophising, rumination and self-blame positively predicted insomnia. Moreover, maladaptive emotion regulation strategies (especially catastrophising) mediated the relationship between resilience and insomnia. The findings suggest the middle-aged and elderly with insomnia tended to employ maladaptive emotion regulation strategies and had lower resilience. Maladaptive emotion regulation strategies buffered the positive effect of resilience on sleep. [ABSTRACT FROM AUTHOR]

Rationale: Currently available PDE2 inhibitors have poor brain penetration that limits their therapeutic utility in the treatment of depression. Hcyb1 is a novel selective PDE2 inhibitor that was introduced more lipophilic groups with polar functionality to the scaffold pyrazolopyrimidinone to improve the blood-brain barrier (BBB) penetration. Our previous study suggested that Hcyb1 increased the neuronal cell viability and exhibited antidepressant-like effects, which were parallel to the currently available PDE2 inhibitor Bay 60-7550. Objectives: The present study investigated whether Hcyb1 protected HT-22 cells against corticosterone-induced neurotoxicity and produced antidepressant-like effects in behavioral tests in stressed mice. Methods: The neuroprotective effects of Hcyb1 against corticosterone-induced cell lesion were examined by cell viability (MTS) assay. The enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis were used to determine the levels of cAMP or cGMP and expression of pCREB or BDNF, respectively, in the corticosterone-treated HT-22 cells. The antidepressant-like effects of Hcyb1 were determined in the tail suspension and novelty suppressed feeding tests in stressed mice. Results: In the cell-based assay, Hcyb1 significantly increased cell viability of HT-22 cells against corticosterone-induced neurotoxicity in a time- and dose-dependent manner. Hcyb1 also rescued corticosterone-induced decreases in both cGMP and cAMP levels, pCREB/CREB and BDNF expression. These protective effects of Hcyb1 were prevented by pretreatment with either the PKA inhibitor H89 or the PKG inhibitor KT5823. Moreover, Hcyb1 reversed acute stress–induced increases in immobility time and the latency to feed in the tail suspension and novelty suppressed feeding tests, respectively, which were prevented by pretreatment with H89 or KT5823. Conclusion: These findings provide evidence that the neuroprotective effects of Hcyb1 are mediated by PDE2-dependent cAMP/cGMP signaling. [ABSTRACT FROM AUTHOR]

Tensile behaviors of Ti/Ni nanolaminate with model-I crack are investigated by molecular dynamics simulations. The Ti/Ni nanolaminates with center crack either in Ti layer or in Ni layer under different loading directions are utilized to systematically study the mechanical performance of the cracked material. The results indicate that pre-existing crack dramatically changes the plastic deformation mechanism of the Ti/Ni nanolaminate. Unlike the initial plastic deformation originating from the interface or weak Ti layer of the crack-free samples, the plastic behavior of cracked Ti/Ni nanolaminate first occurs at the crack tip due to the local stress concentration. Subsequent plastic deformation is dominated by the interaction between the crack and interface. The Ti/Ni interface not only impedes the movement of the initial plastic deformation carriers (dislocation, slip band, and deformation twinning) from the crack tip, but also promotes the movement of interfacial dislocations in the tension process. Microstructure evolution analysis further confirms that the plastic deformation mechanism transition is ascribed to the orientation-dependent tensile behavior at the crack tip, which is intrinsically attributed to the anisotropy of the certain crystal structure and loading direction of the cracked Ti/Ni nanolaminate. In addition, by analyzing the effects of different plastic deformation carriers on crack propagation in specific crystal, it can be discovered that the interfacial dislocations moving towards the crack tip can further promote the crack growth. [ABSTRACT FROM AUTHOR]

Although the energy consumption of reported neuromorphic computing devices inspired by biological systems has become lower than traditional memory, it still remains greater than bio‐synapses (≈10 fJ per spike). Herein, a flexible MoS2‐based heterosynapse is designed with two modulation modes, an electronic mode and a photoexcited mode. A one‐step mechanical exfoliation method on flexible substrate and low‐temperature atomic layer deposition process compatible with flexible electronics are developed for fabricating wearable heterosynapses. With a pre‐spike of 100 ns, the synaptic device exhibits ultralow energy consumption of 18.3 aJ per spike in long‐term potentiation and 28.9 aJ per spike in long‐term depression. The ultrafast speed and ultralow power consumption provide a path for a neuromorphic computing system owning more excellent processing ability than the human brain. By adding optical modulation, a modulatory synapse is constructed to dynamically control correlations between pre‐ and post‐synapses and realize complex global neuromodulations. The novel wearable heterosynapse expands the accessible range of synaptic weights (ratio of facilitation ≈228%), providing an insight into the application of wearable 2D highly efficient neuromorphic computing architectures. [ABSTRACT FROM AUTHOR]

Background: Surgical treatment is indicated for unstable acromioclavicular (AC) joint dislocation. The hook plate (HP) technique is a commonly used treatment method, but the use of the suture button (SB) technique is increasing. Purpose: To conduct a meta-analysis of clinical studies evaluating patient outcomes between the SB and HP techniques for acute unstable AC joint dislocation. Study Design: Meta-analysis. Methods: A literature search of the Embase, PubMed, and Cochrane Library databases was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Cohort studies and case-control studies comparing the SB and HP procedures for acute unstable AC joint dislocation were included. Statistical analysis was performed with RevMan (v 5.3.5). Results: Eight clinical studies that met the inclusion criteria were identified and included a total of 204 patients treated with the SB technique and 195 patients with the HP technique. Patients treated with the SB technique had a higher Constant score (mean difference [MD], 3.95; 95% CI, 1.20-6.70; P =.005) and a lower visual analog scale pain score (MD, –0.75; 95% CI, –1.12 to 0.37; P <.0001) when compared with the HP technique. No significant differences in operation time (MD, –0.38; 95% CI, –7.14 to 6.37; P =.91), coracoclavicular distance (MD, –0.07; 95% CI, –0.49 to 0.35; P =.75), complications (odds ratio, 0.59; 95% CI, 0.22-1.54; P =.28), and loss of reduction (odds ratio, 2.55; 95% CI, 0.66-9.83; P =.17) were found between the SB and HP techniques. The subgroup analysis showed that the arthroscopic SB technique resulted in a higher Constant score (MD, 6.75; 95% CI, 4.21-9.29; P <.00001) as compared with the HP technique, but no differences were observed between the open SB and HP techniques (MD, 0.69; 95% CI, –0.82 to 2.20; P =.37). Conclusion: This meta-analysis demonstrated that the SB technique resulted in better functional outcomes and a reduced visual analog scale pain score when compared with the HP technique. However, for operation time, coracoclavicular distance, complications, and loss of reduction, there were no statistically significant differences between the techniques. Compared with the open procedure, arthroscopic SB may be superior for better functional outcomes. [ABSTRACT FROM AUTHOR]

The tawny crazy ant (Nylanderia fulva) is a new invasive pest in the United States. At present, its management mainly relies on the use of synthetic insecticides, which are generally ineffective at producing lasting control of the pest, necessitating alternative environmentally friendly measures. In this study, we evaluated the feasibility of gene silencing to control this ant species. Six housekeeping genes encoding actin (NfActin), coatomer subunit β (NfCOPβ), arginine kinase (NfArgK), and V‐type proton ATPase subunits A (NfvATPaseA), B (NfvATPaseB) and E (NfvATPaseE) were cloned. Phylogenetic analysis revealed high sequence similarity to homologs from other ant species, particularly the Florida carpenter ant (Camponotus floridanus). To silence these genes, vector L4440 was used to generate six specific RNAi constructs for bacterial expression. Heat‐inactivated, dsRNA‐expressing Escherichia coli were incorporated into artificial diet. Worker ants exhibited reduced endogenous gene expression after feeding on such diet for 9 d. However, only ingestion of dsRNAs of NfCOPβ (a gene involved in protein trafficking) and NfArgK (a cellular energy reserve regulatory gene in invertebrates) caused modest but significantly higher ant mortality than the control. These results suggest that bacterially expressed dsRNA can be orally delivered to ant cells as a mean to target its vulnerabilities. Improved efficacy is necessary for the RNAi‐based approach to be useful in tawny crazy ant management. [ABSTRACT FROM AUTHOR]

Modified Aedes aegypti mosquitoes are being mass-reared for release in disease control programs around the world. Releases involving female mosquitoes rely on them being able to seek and feed on human hosts. To facilitate the mass-production of mosquitoes for releases, females are often provided blood through artificial membrane feeders. When reared across generations there is a risk that mosquitoes will adapt to feeding on membranes and lose their ability to feed on human hosts. To test adaptation to membrane feeding, we selected replicate populations of Ae. aegypti for feeding on either human arms or membrane feeders for at least 8 generations. Membrane-selected populations suffered fitness costs, likely due to inbreeding depression arising from bottlenecks. Membrane-selected females had higher feeding rates on membranes than human-selected ones, suggesting adaptation to membrane feeding, but they maintained their attraction to host cues and feeding ability on humans despite a lack of selection for these traits. Host-seeking ability in small laboratory cages did not differ between populations selected on the two blood sources, but membrane-selected females were compromised in a semi-field enclosure where host-seeking was tested over a longer distance. Our findings suggest that Ae. aegypti may adapt to feeding on blood provided artificially, but this will not substantially compromise field performance or affect experimental assessments of mosquito fitness. However, large population sizes (thousands of individuals) during mass rearing with membrane feeders should be maintained to avoid bottlenecks which lead to inbreeding depression. [ABSTRACT FROM AUTHOR]

Metastasis is responsible for 90% of all cancer-related deaths in humans, and the development of a rapid and promising solution for an early diagnosis of metastasis is required. The present study proposed a promising method combined with scanned laser pico-projection technique and typical texture feature (i.e., contrast, correlation, energy, entropy, and homogeneity) extraction of gray-level co-occurrence matrix (GLCM) image processing model to classify the low- and high-metastatic cancer cells using five common cancer adenocarcinoma cell line pairs (i.e., HeLa/HeLa-S3, CL1-0/CL1-5, OVTW59-P0/OVTW59-P4, and CE81T-FNlow/CE81T-FNhigh cell lines). Highly metastatic cancer cells essentially have the highest levels of disorder. Both contrast and entropy refer to the degree of disorder, and energy and homogeneity refer to the degree of uniformity. These four texture features can be effective evaluation indexes for disorder in cancer cells responding to metastatic ability. Texture feature extraction forms reflection images, which are recorded with scanned laser pico-projection system; they effectively bridge the gap in information derived from transmission images. The low- and high-metastatic cancer cells are statistically and effectively classified from the texture feature of GLCM through transmission and reflection images taken with scanned laser pico-projection system. In particular, it only requires several seconds after producing a confluent monolayer of cells and achieves the rapid method with a more reliable diagnostic performance for metastatic ability of cancer cells in vitro or ex vivo. [ABSTRACT FROM AUTHOR]