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According to international cancer data, breast cancer (BC) is the leading type of cancer in women. Although significant progress has been made in treating BC, metastasis and drug resistance continue to be the primary causes of mortality for many patients. Reactive oxygen species (ROS) play a dual role in vivo: normal levels can maintain the body's normal physiological function; however, high levels of ROS below the toxicity threshold can lead to mtDNA damage, activation of proto-oncogenes, and inhibition of tumor suppressor genes, which are important causes of BC. Differences in the production and regulation of ROS in different BC subtypes have important implications for the development and treatment of BC. ROS can also serve as an important intracellular signal transduction factor by affecting the antioxidant system, activating MAPK and PI3K/AKT, and other signal pathways to regulate cell cycle and change the relationship between cells and the activity of metalloproteinases, which significantly impacts the metastasis of BC. Hypoxia in the BC microenvironment increases ROS production levels, thereby inducing the expression of hypoxia inducible factor-1α (HIF-1α) and forming "ROS- HIF-1α-ROS" cycle that exacerbates BC development. Many anti-BC therapies generate sufficient toxic ROS to promote cancer cell apoptosis, but because the basal level of ROS in BC cells exceeds that of normal cells, this leads to up-regulation of the antioxidant system, drug efflux, and apoptosis inhibition, rendering BC cells resistant to the drug. ROS crosstalks with tumor vessels and stromal cells in the microenvironment, increasing invasiveness and drug resistance in BC. • Reactive oxygen species are involved in the development of breast cancer through various means such as DNA mutation and signaling. • Both the reduction of reactive oxygen species below physiological levels and the increase of production to toxic levels can treat breast cancer. • Reactive oxygen species are important in the development and treatment of different subtypes of breast cancer. [ABSTRACT FROM AUTHOR]

Conditionally replicating viruses (CRVs) are a safer option than attenuated vaccines and more effective than inactivated vaccines as they can activate the immune system, both innate and adaptive immune responses. Destabilizing domain fusion, proteolysis-targeting chimeras, and premature termination codon (PTC) read through are among the most promising strategies for CRVs. Targeted protein degradation technologies are more suitable for large-genome viruses and segmented RNA viruses. PTC read-through strategies have minimal possibility of influencing the functionality of the targeted virus and therefore may also perform well in small-genome viruses. Anticodon engineered tRNA technology makes PTC strategies more practical. Conditionally replicating viruses (CRVs) are a type of virus with one or more essential gene functions that are impaired resulting in the disruption of viral genome replication, protein synthesis, or virus particle assembly. CRVs can replicate only if the deficient essential genes are supplied. CRVs are widely used in biomedical research, particularly as vaccines. Traditionally, CRVs are generated by creating complementary cell lines that provide the impaired genes. With the development of biotechnology, novel techniques have been invented to generate CRVs, such as targeted protein degradation (TPD) technologies and premature termination codon (PTC) read-through technologies. The advantages and disadvantages of these novel technologies are discussed. Finally, we provide perspectives on what challenges need to be overcome for CRVs to reach the market. [ABSTRACT FROM AUTHOR]

Increased metabolic stress during early lactation results in damage of mitochondria and inflammatory responses in bovine mammary epithelial cells, both of which could be aggravated by inhibition of mitophagy. PTEN-induced putative kinase 1 (PINK1)-mediated mitophagy is essential in the removal of damaged mitochondria and the regulation of inflammatory responses. The aim of the present study was to elucidate the role of PINK1-mediated mitophagy on mitochondrial damage and inflammatory responses in bovine mammary epithelial cells challenged with lipopolysaccharide (LPS). Exogenous LPS activated mitophagy and led to lower protein abundance of oxidative phosphorylation (OXPHOS) complexes (COI–V) and lower oxygen consumption rate (OCR) along with increased mitochondrial reactive oxygen species (Mito-ROS) content. These effects were also associated with increased protein abundance of Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) in a time-dependent manner. Pretreatment with 3-Methyladenine (3-MA) or knockdown of PINK1 aggravated the downregulation of COI–V protein abundance, the increase in Mito-ROS content, and the protein abundance of NLRP3, Cleaved-Caspase-1 and IL-1β induced by LPS. Overexpression of PINK1 activated mitophagy and alleviated LPS-induced NLRP3 inflammasome activation by reducing Mito-ROS production. Overall, the data suggested that PINK1-mediated mitophagy is a crucial anti-inflammatory mechanism that removes damaged mitochondria in bovine mammary epithelial cells experiencing an increased inflammatory load. • Exogenous LPS induced mitochondrial damage and inflammation in MAC-T cells. • Overexpression of PINK1 enhanced LPS-induced mitophagy in MAC-T cells. • PINK1-mediated mitophagy alleviated inflammation by remove damaged mitochondria. [ABSTRACT FROM AUTHOR]

An amine-tagged bimetallic MOF-74 nanozyme with ultrathin structure and improved peroxidase-mimicking activity has been constructed through a layered double hydroxide (LDH) directed method for the ultrasensitive detection of analytes from bioactive small molecules (H 2 O 2 and ascorbic acid), biomacromolecules (alkaline phosphatase, ascorbic acid oxidase, and α-glucosidase), and pathogenic bacteria (Staphylococcus aureus). [Display omitted] • Ultrathin bimetallic MOF-74 nanozyme was prepared using LDH as template. • The nanozyme showed boosted catalytic activity and stability. • The MOF based platform was used for detection of various analytes. • The strategy was successfully applied in real biological samples. The exquisite design of nanostructures for enzyme-biocatalyzed active sites mimicking has become a prospective method to significantly boost biocatalytic properties, which is profitable to response amplification for bioanalysis scenarios. Metal-organic frameworks (MOFs) with customizable compositions, diverse microstructures and open catalytic sites are considered to deal with challenges in conventional materials of unfriendly microenvironment and inexact coordination. Herein, by combining a metal doping and post-synthetic modification approach, amine-tagged Fe-Ni bimetallic MOF-74 nanozyme (FeNi-MOF-74-NH 2) with ultrathin structure and improved peroxidase-mimicking bioactivity is synthesized through a layered double hydroxide (LDH) directed method. The boosted biocatalytic property largely benefits from the synergistic effects of Fe-Ni species, attributing to the dual mechanism (electron transfer and generation of hydroxyl radicals). On the basis of the enhanced enzyme-mimicking property and accessible amino functionalization of FeNi-MOF-74-NH 2 , versatile applications were carried out for the ultrasensitive detection of analytes from bioactive small molecules (H 2 O 2 and ascorbic acid), biomacromolecules (alkaline phosphatase, ascorbic acid oxidase, and α-glucosidase), and pathogenic bacteria (Staphylococcus aureus). The nanozyme-based biosensing platform without complex enzymatic techniques serves as a proof-of-concept to facilitate the application of MOF nanozymes in biochemical analysis, clinical diagnosis, and biomedical research. [ABSTRACT FROM AUTHOR]

The tectonic transition from oceanic subduction to continental collision is a fundamental process during orogenesis. Yet, the nature of this transition and its deep geodynamic processes for the southern Tibetan Plateau remain contentious. This study presents zircon U-Pb-Hf isotopes, whole-rock geochemistry, and Sr Nd isotopes for a quartz diorite intrusion and bimodal dykes from Dagze, combined with compiled data from the southern Lhasa subterrane, to reveal the geodynamic processes of late-stage of Neo-Tethyan subduction. Most of Dagze samples were emplaced between 66 and 64 Ma, while muscovite granite aplite dykes were emplaced between 64 and 60 Ma. They exhibit relatively uniform, depleted Sr Nd isotopes, with ε Nd (t) values ranging from +2.2 to +4.0, positive zircon ε Hf (t) values, and young depleted mantle model ages. Both exhibit compositional characteristics of subduction-related arc magma, marked by the enrichment of large ion lithophile elements and the depletion of high field strength elements. The mafic dykes with relatively low SiO 2 , high MgO, Cr, Ni, possibly originated from a fluid-metasomatized depleted mantle. The quartz diorite intrusion with low MgO, Cr, and Ni was generated by partial melting of sub-arc lithospheric mantle and experienced subsequent fractional crystallization of amphibole, clinopyroxene and orthopyroxene. The granitic dykes originated from partial melting of Gangdese juvenile crust and experienced fractional crystallization dominated by plagioclase. We suggest that the slab rollback and continental collision conjointly controlled the evolution of the latest Cretaceous to Paleocene Himalayan–Tibetan orogeny. Slab rollback of Neo-Tethys commenced around 70 Ma, triggering the partial melting of depleted mantle and juvenile crust, and this process resulted in the formation of Dagze diorites and bimodal dykes with arc affinity. • Diorite intrusion and mafic dykes originated from a fluid-metasomatized depleted mantle. • Granitic dykes originated from Gangdese juvenile crust and experienced fractional crystallization. • Slab rollback of the Neo-Tethys oceanic slab commenced around 70 Ma. [ABSTRACT FROM AUTHOR]

In insects, vision is crucial in finding host plants, but its role in nocturnal insects is largely unknown. Vision involves responses to specific spectra of photon wavelengths and opsins plays an important role in this process. Long-wavelength sensitive opsin (LW opsin) and blue-sensitive opsin (BL opsin) are main visual opsin proteins and play important in behavior regulation.We used CRISPR/Cas9 technology to mutate the long-wavelength-sensitive and blue wavelength-sensitive genes and explored the role of vision in the nocturnal invasive pest Tuta absoluta. Light wave experiments revealed that LW2 (−/−) and BL (−/−) mutants showed abnormal wavelength tropism. Both LW2 and BL mutations affected the preference of T. absoluta for the green environment. Mutations in LW2 and BL are necessary to inhibit visual attraction. The elimination of LW2 and BL affected the preference of leaf moths for green plants, and mutations in both induced a preference in moths for white plants. Behavioral changes resulting from LW2 (−/−) and BL (−/−) mutants were not affected by sense of smell, further supporting the regulatory role of vision in insect behavior. To the best of our knowledge, this is the first study to reveal that vision, not smell, plays an important role in the host-seeking behavior of nocturnal insects at night, of which LW2 and BL opsins are key regulatory factors. These study findings will drive the development of the "vision-ecology" theory. [ABSTRACT FROM AUTHOR]

Nonlinear operator theory is an important area of nonlinear functional analysis. This area encompasses diverse nonlinear problems in many areas of mathematics, the physical sciences and engineering such as monotone operator equations, fixed point problems and more. In this work we are concern with the problem of finding a common solution of a monotone operator equation and fixed point of a nonexpansive mapping in real Hilbert spaces. Derived from dynamical systems, a simple inertial forward-backward splitting method for solving the problem is presented and analyzed under mild and standard assumptions. Some numerical examples in real-world and comparisons with related works, illustrate the theoretical advantages as well the potential applicability of the proposed scheme. [ABSTRACT FROM AUTHOR]

Many studies have been conducted over the last few decades to understand better the functions of IRF3 and IRF7 in antiviral immune responses. However, the precise underlying molecular mechanism of IRF1-mediated immune response remains largely unknown. Recent studies indicate that IRF1 exerts strong antiviral activities against several viral infections through diverse mechanisms, both in IFN-dependent and IFN-independent manners. Nevertheless, the efficacy and kinetics of inducing IFNs and ISGs remain unknown. Here we summarize the recent advances in IRF1 research and highlight its potential roles in initiating IFN immune responses and subsequent IRF1-triggering antiviral responses. Challenges regarding the IFN positive feedback mediated by IRF7 during infection will be discussed; this classical loop may also be mediated in part by IRF1. Therefore, we propose a revised model that may help decipher the functional roles of IRF1 in antiviral immunity. [Display omitted] • IRF1 induces both IFN production and basal level of ISGs. • IRF1 involves an interferon induction in an IRF3 and IRF7 independent manner. • IRF1 is involved in the modification of JAK1, STAT1. • IRF1 is involved in the epigenetic regulation of ISGs. • Viruses evolve to antagonize the IRF1 mediated signaling pathway. [ABSTRACT FROM AUTHOR]

Previous studies have shown that optimal blood pressure (BP) control is necessary to outcomes in patients with acute myocardial infarction (AMI). Acute left ventricular MI is a prevalent type of AMI with poor prognosis. We aimed to analyze the associations between BP control in the first 7 days of hospitalization and long-term mortality specific to patients with isolated left ventricular MI. A total of 3108 acute left ventricular MI patients were included in this analysis. The average BP on the first seven days of hospitalization was categorized into 10-mmHg increments. The primary and secondary outcomes were all-cause death and cardiac death, respectively. Cox models were used to assess the association of outcomes with BP during hospitalization. The median length-of-stay was 7 (IQR 6–10) days. The relationship between systolic BP (SBP) or diastolic BP (DBP) followed a U-shaped curve association with outcomes. All-cause mortality was higher in patients with lower SBP (≤90 mmHg) (adjusted hazard ratios (HRs) 7.12, 95% confidence interval (CI) 3.13–16.19; p < 0.001) and DBP (<60 mmHg) (HR 1.76, 95% CI 1.14–2.71; p = 0.011) [reference: 110 < SBP ≤120 mmHg; 70 < DBP ≤ 80 mmHg], respectively. Furthermore, primary outcome was higher in patients with higher SBP (>130 mmHg) (HR 1.51, 95% CI 1.12–2.03; p = 0.007) and DBP (>80 mmHg) (HR 1.61, 95% CI 1.20–2.18; p = 0.002), respectively. Maintaining a SBP from 90 to 130 mmHg and a DBP from 60 to 80 mmHg may be beneficial to patients with acute left ventricular MI in the long run. • Our study was firstly focused on acute left ventricular myocardial infarction (MI). • Mean BP in the 7 days after acute left MI were associated with long-term mortality. • Maintaining SBP (90-130 mmHg) and DBP (60-80 mmHg) in the 7 days after acute left MI may be beneficial. • Our data proposed an valuable hypothesis to better clinical outcomes in acute left ventricular MI. [ABSTRACT FROM AUTHOR]

Background: Early detection of gait abnormalities is critical for preventing severe injuries in future falls. The timed up and go (TUG) test is a commonly used clinical gait screening test; however, the interpretation of its results is limited to the TUG total time.Research Question: What is diagnostic accuracy of the low-cost, markerless, automated gait analyzer, with the aid of vision-based artificial intelligence technology, which extract gait spatiotemporal features and screen for abnormal walking patterns through video recordings of the TUG test?Methods: Our dataset contained retrospective data from outpatients from the Department of Neurology or Rehabilitation of two tertiary hospitals in Shanghai. A panel of three expert neurologists specialized in movement disorders reviewed the gait performance in each TUG video, and labeled them separately, with the most commonly assigned label being used as the reference standard. The gait analyzer performed the AlphaPose algorithm to track the human joint position and calculated the spatiotemporal parameters by filtering and double-threshold signal detection. Gait spatiotemporal features and expert labels were input into machine learning models, and the accuracy of each model was tested with leave-one-out cross-validation (LOOCV).Results: A total of 284 participants were recruited. Among these, 100 were labeled as having abnormal gait performance by experts. The Naive Bayes classifier achieved the best performance with a full-data accuracy of 90.14% and a LOOCV accuracy of 89.08% for screening abnormal gait performance.Significance: This study is the first to investigate the accuracy of a vision-based intelligent gait analyzer for screening abnormal clinical gait performance. By virtue of a pose estimation algorithm and machine learning models, our intelligent gait analyzer can detect abnormal walking patterns approximate to judgements made by experienced neurologists, which is expected to be a supplementary gait assessment protocol for basic-level doctors in the future. [ABSTRACT FROM AUTHOR]

• Characterized the vermicular graphite rate and tensile strength in vermicular cast iron using NUT. • Dislocation string model and metallographic observation have been used to explain the change in the ANP. • A new relationship between vermicular graphite rate, ANP, and tensile strength has been established by experiments. Ultrasonic techniques have been widely used to detect the percentage of vermicular graphite, defects, etc. in vermicular graphite cast iron. The linear ultrasonic velocity method is the main ultrasonic method for characterizing vermicular graphite rate and tensile strength in the current study, however, it is often easy to misjudge the vermicular graphite rate due to its insignificant variation. This study explores the feasibility of using the nonlinear ultrasonic technique (NUT) to characterize the vermicular graphite rate and tensile strength. Based on the longitudinal critically refracted (LCR) wave detection model, an experimental study to detect the vermicular graphite rate and tensile strength of vermicular graphite cast iron is carried out using the nonlinear ultrasonic harmonic method, and compared with the ultrasonic velocity method. The experiment results show that the relative nonlinear parameter of the LCR wave decreases along with the increase of vermicular graphite rate and increases along with the increase of tensile strength, and it has higher detection sensitivity and resolution than ultrasonic velocity by analyzing the obtained data. The increase in the acoustic nonlinearity parameter (ANP) is related to the increase in the number of grain boundaries in the microstructure. Therefore, the relationship among microstructure, ANP, and mechanical properties of vermicular graphite cast iron can be established, and it's promising that a new approach might be developed for quickly detecting the vermicular graphite rate and corresponding tensile strength with the NUT. [ABSTRACT FROM AUTHOR]

The limited visible light response range and fast recombination rate of photoinduced carriers restrict the photocatalytic performance of Bi 2 WO 6. Herein, a novel low temperature hydrothermal approach was developed to construct the Bi 2 WO 6 /Bi 2 O 4 heterojunction with WO 3 and NaBiO 3 •2 H 2 O powders as precursors and the latter as the only bismuth source. During the hydrothermal reaction, WO 3 first reacts with NaBiO 3 · 2 H 2 O to generate Bi 2 WO 6 and then the residual NaBiO 3 ·2 H 2 O converts into Bi 2 O 4 , in-situ forming the Bi 2 WO 6 /Bi 2 O 4 heterojunction with the co-shared Bi atoms. The content of Bi 2 WO 6 in the heterostructure can be facilely modulated by changing the amount of WO 3 added. The construction of Bi 2 WO 6 /Bi 2 O 4 heterojunction could not only extend the spectral response range but also improve the separation efficiency of photoinduced charges. Consequently, the photocatalytic degradation performance to tetracycline (phenol) for the optimal Bi 2 WO 6 /Bi 2 O 4 heterostructure is 5.19 and 1.77 times (4.75 and 1.66 times) higher than that of single Bi 2 WO 6 and Bi 2 O 4 under visible light, respectively. The capture experiments of active species and electron spin resonance spectra demonstrate that radicals (·O 2 -) and holes (h +) are the first and second important active species, respectively, during the catalytic degradation. Our work provides a new idea for the fabrication of high-performance Bi 2 WO 6 -based junction photocatalysts. [Display omitted] [ABSTRACT FROM AUTHOR]

The blending of poly (L-lactic acid) (PLLA) and poly (D-lactic acid) (PDLA) achieves an effective transformation of properties based on the formation of interchain hydrogen bonds. Therefore, it is important to study the stereo-complex (SC) system. We studied the solution crystallization of PLLA/PDLA blends based on the sensitivity of terahertz (THz) spectroscopy to hydrogen bonds. The results revealed an abnormal red-shift in the characteristic peak frequency of the blends with the increase of PLLA, which is attributed to the difference in chain stacking of the main components in the blends. Moreover, we believe that the peak height of the SC at 1.43 THz is an accurate index reflecting the interchain hydrogen bonds in the case of blending ratio changes. When the blend ratio is determined, we found that the blue shift of this peak frequency corresponded to the weakening of interchain hydrogen bonds. The results show that THz spectroscopy can effectively observe the solution crystallization behavior of blends, and its different characteristic indexes contain the information of interaction and aggregation structure. [Display omitted] • With the increase of PLLA, the abnormal redshift of peak at 1.43 THz of blends is due to the difference of chain stacking of main components. • The characteristic peak height at 1.43 THz of blends is an accurate indicator of interchain hydrogen bond when the blending ratio changes. • The blue shift of peak at 1.43 THz of blends corresponds to the weakening of interchain hydrogen bond when the blending ratio is determined. [ABSTRACT FROM AUTHOR]

The rice stem borer (RSB, Chilo suppressalis) is a significant agricultural pest that mainly depends on chemical control. However, it has grown to varied degrees of pesticide resistance, which poses a severe threat to rice production and emphasizes the need for safer, more efficient alternative pest management strategies. Here, in vitro and in vivo experiments analyses reveal miR-1579 binds to the critical transcription factor Krüppel homologue 1 (Kr-h1) and negatively regulates its expression. Overexpression of miR-1579 in larvae with significantly lower levels of Kr-h1 was associated with a decline in larval growth and survival. Furthermore, in female pupae, miR-1579 overexpression led to abnormalities in ovarian development, suggesting that targeting miR-1579 could be a potential management strategy against C. suppressalis. Therefore, we generated transgenic rice expressing miR-1579 and screened three lines that had a single copy of highly abundant mature miR-1579 transcripts. Expectedly, fed with transgenic miR-1579 rice lines were significantly lower survival rates in larvae and high levels of resistance to damage caused by C. suppressalis infestation. These findings suggest that miRNA-mediated RNAi could provide an effective and species-specific strategy for C. suppressalis control. • The critical transcription factor Kr-h1 regulates larval growth of Chilo suppressalis. • miR-1579 directly binds to Kr-h1 to modulate larval development and female reproduction. • Transgenic rice overexpressing miR-1579 shows high resistance to C. suppressalis and remaining non-target insect safe. [ABSTRACT FROM AUTHOR]

Bovine mammary epithelial cells undergo an increase in metabolic rate, mitochondrial dysfunction, and oxidative stress after calving. Nuclear factor erythroid 2-related factor 2 (NFE2L2), a master regulator of cellular redox homeostasis, plays crucial roles in the regulation of mitochondrial function. The objective of this study was to investigate the role of NFE2L2 on mitochondrial function in bovine mammary epithelial cells under hyperlipidemic conditions. Three experiments were conducted as follows: (1) the immortalized bovine mammary epithelial cell line MAC-T was treated with various concentrations of free fatty acids (FFA; 0, 0.6, 1.2, or 2.4 m M) for 24 h to induce stress; (2) MAC-T cells were transfected with small interfering RNA targeting NFE2L2 (si-NFE2L2) and scrambled nontarget negative control (si-Control) for 48 h; and (3) MAC-T cells were pretreated with 10 μ M sulforaphane (SFN), an activator of NFE2L2, for 24 h followed by treatment with 1.2 m M FFA for an additional 24 h. Results indicated that exogenous FFA challenge induced linear and quadratic increases in concentrations of mitochondrial reactive oxygen species (ROS). Compared with 0 m M FFA, mitochondrial membrane potential, mRNA abundance of oxidative phosphorylation complexes (CO I-V), protein abundance of nuclear respiratory factor 1 (NRF1), peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α), mitochondrial transcription factor A (TFAM), and NFE2L2 along with the contents of ATP, mitochondrial DNA (mtDNA), and total mitochondria were greater in the MAC-T challenged with 0.6 m M FFA group, but lower in the 1.2 and 2.4 m M FFA cultures. Knockdown of NFE2L2 via small interfering RNA led to greater mitochondrial ROS content and lower mitochondrial membrane potential along with contents of ATP, mtDNA, and total mitochondria. The SFN pretreatment upregulated protein abundance of NFE2L2 and attenuated the downregulation of NFE2L2 induced by FFA. Pretreatment with SFN attenuated the downregulation induced by FFA of PGC-1α, NRF1, and TFAM protein abundance along with contents of mtDNA and total mitochondria. Furthermore, SFN pretreatment attenuated the upregulation of mitochondrial ROS content, the downregulation of mitochondrial membrane potential, and the decreases in ATP, mtDNA, and mitochondrial content induced by FFA. Overall, data indicated that FFA inhibit NFE2L2, resulting in mitochondrial dysfunction and ROS production in bovine mammary epithelial cells. Thus, NFE2L2 may be a promising therapeutic target against metabolic challenge-driven mitochondrial dysfunction and oxidative stress in bovine mammary epithelial cells. [ABSTRACT FROM AUTHOR]

• PI3K inhibition induces tau hyperphosphorylation. • PI3K inhibition disturbs cerebral glucose metabolism. • PI3K inhibition impairs LTP of DG-CA1 and synaptic plasticity. As the symbolic pathological changes of Alzheimer's disease (AD), hyperphosphorylated tau and amyloid plaque play important roles in the progression of the disease. In AD patients, the neural activity in default mode network is abnormal at different stages of the disease, and showed a hypoconnective status. Inhibition of phosphatidylinositol-3-kinase (PI3K) activates glycogen synthase kinase 3 beta (GSK-3β) and induces tau phosphorylation. We speculated that inhibiting cerebral PI3K altered the glucose metabolism in DMN. We aimed to explore the impacts of PI3K inhibition on tau phosphorylation, cerebral glucose metabolism, and synaptic plasticity. We injected wortmannin, an inhibitor of PI3K, lateral ventricularly in rats to mimic the pathology of AD. Immunohistochemistry was carried out to analyze the expression of phosphorylated tau. Region-specific glucose metabolism in the brain was analyzed using 18F-FDG PET imaging. In vivo long-term potentiation (LTP) in the hippocampus was detected to assess the synaptic plasticity. The results show that the phosphorylated tau at T231 increased and the hippocampal LTP was suppressed 24 h after wortmannin administration. In the DMN, glucose uptake was significantly high, indicating a neural activity disturbance. We conclude that targeting PI3K-GSK-3β pathway to mimic AD tau pathology interrupted the glucose metabolism of DMN brain regions. [ABSTRACT FROM AUTHOR]

Ketosis is a serious metabolic disorder characterized by systemic and hepatic oxidative stress, inflammation, and apoptosis, as well as reduced milk yield. Because of the paucity of data on mammary responses during ketosis, the aim of this study was to evaluate alterations in oxidative stress, NF-κB signaling, NLRP3 inflammasome, and caspase apoptotic pathways in mammary gland of dairy cows with ketosis. Blood, mammary gland tissue, and milk samples were collected from healthy cows [Control, blood concentration of β-hydroxybutyrate (BHB) <0.6 m M , n = 10] and cows with subclinical ketosis (SCK, blood concentration of BHB >1.2 m M and <3 m M , n = 10) or clinical ketosis (CK, blood concentration of BHB >3 m M , n = 10) at median 8 d in milk (range = 6–12). Compared with Control, serum concentration of glucose was lower (3.91 vs. 2.86 or 2.12 m M) in cows with SCK or CK, whereas concentrations of fatty acids (0.25 vs. 0.57 or 1.09 m M) and BHB (0.42 vs. 1.81 or 3.85 m M) were greater. Compared with Control, the percentage of milk fat was greater in cows with SCK or CK. In contrast, the percentage of milk protein was lower in cows with SCK or CK. We detected no differences in milk lactose content across groups. Compared with Control, activities of glutathione peroxidase, superoxide dismutase, and catalase were lower in mammary gland tissue of cows with SCK or CK. In contrast, concentrations of hydrogen peroxide and malondialdehyde were greater in cows with SCK or CK. Compared with Control, mRNA abundances of TNFA , IL6 , and IL1B were greater in mammary tissues of cows with SCK or CK. In addition, activity of IKKβ and the ratio of phosphorylated inhibitor of κBα to IκBα, and of phosphorylated NF-κB p65 to NF-κB p65, were also greater in mammary tissues of cows with SCK or CK. Subclinical or clinical ketosis also led to greater activity of caspase 1 and protein abundance of caspase 1, NLRP3, Bax, caspase 3, and caspase 9. In contrast, abundance of the antiapoptotic protein was lower in SCK or CK cows. The data indicate that the mammary gland of SKC or CK cows undergoes severe oxidative stress, inflammation, and cell death. [ABSTRACT FROM AUTHOR]

• A new method for studying the crystal structure difference between phenylalanine and its fluorinated derivatives was proposed. • The effect of the introduction of fluorine atoms at different positions on the benzene ring on the dielectric properties of phenylalanine was explained. • The number and type of hydrogen bonds in L-Phenylalanine , 3-Fluoro- L-Phenylalanine and 4-Fluoro- L-Phenylalanine were observed. 3-Fluoro-L-Phenylalanine (3-F-L-Phe) and 4-Fluoro-L-Phenylalanine (4-F-L-Phe) are fluorinated derivatives of L-Phenylalanine (L-Phe) that hold significant medical applications. To investigate the impact of introducing fluorine atoms on the structure of L-Phe, this study employed terahertz (THz) spectroscopy to distinguish three crystal structure differences. A comparative analysis of the absorption peaks of 3-F-L-Phe and 4-F-L-Phe with that of L-Phe revealed varying degrees of red shift and blue shift. The dielectric loss analysis demonstrated that the substitution of fluorine atoms in different positions of the benzene ring changes the crystal structure and electric dipole moment. By combining lattice network and vibration mode comparative analysis, the study concluded that the differences in the spectrum could be attributed to variations in the hydrogen bond network and changes in the unit cell volume. These findings highlight the effectiveness of using terahertz time domain spectroscopy (THz-TDS) and solid-state density functional theory (DFT) as a new method for the qualitative analysis of fluorinated amino acid derivatives. [Display omitted] [ABSTRACT FROM AUTHOR]

• Establish a unified multi-modal target tracking framework based on joint spatiograms. • Extend the spatiogram from single modality tracking to multi-modality tracking. • Design a fast MIMO fuzzy system to adaptively adjust the weight of each modality. • Develop a model update scheme based on particle filter. Integrating multiple different yet complementary modalities has been proved to be an effective way for boosting tracking performance. Many previous works just consider the fusion of different features from identical image or identical features from images with different spectrum alone, which makes them be quite distinct from each other and be hard to be integrated naturally. In this study, we propose a unified tracking framework to integrate multiple different modalities via innovative use of spatiogram, where the spatiogram is formed by weighting each bin of histogram with the mean and covariance of the locations of the pixels that contribute to that bin. Specifically, each modal target and its candidate are first represented by second-order spatiogram, and their similarity is measured by the weighted Bhattacharayya coefficient. Next, an objective function is built by integrating all modal similarities, then a joint center-shift formula of the target is gained by performing Taylor expansion and gradient minimization on the objective function. Finally, the optimal target location is gained recursively by applying the mean shift procedure. Besides, a fast fuzzy logic system is designed to adaptively adjust the weight of each modality, and a model update scheme based on particle filter is developed to capture the appearance variations. Our framework allows the modality to be original gray of pixel or other extracted feature from single image or different spectral images, and provides the flexibility to arbitrarily add or remove modality. Experimental results on three challenging public datasets demonstrate clearly the robustness and effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

• Cell-type specific expression of the stimulatory subunit hM3Dq in oxytocin neurons of the rat hypothalamus. • Chemogenetic excitation of oxytocin neurons increases Ca2+ dynamics, and evokes central and peripheral oxytocin secretion. • At behavioral level, chemogenetic activation of hypothalamic oxytocin neurons promotes social motivation and anxiolysis. • Therefore, we advise to administer Clozapine N-oxide 30-60 min before the start of the experiment. Chemogenetics provides cell type-specific remote control of neuronal activity. Here, we describe the application of chemogenetics used to specifically activate oxytocin (OT) neurons as representatives of a unique class of neuroendocrine cells. We injected recombinant adeno-associated vectors, driving the stimulatory subunit hM3Dq of a modified human muscarinic receptor into the rat hypothalamus to achieve cell type-specific expression in OT neurons. As chemogenetic activation of OT neurons has not been reported, we provide systematic analysis of the temporal dynamics of OT neuronal responses in vivo by monitoring calcium fluctuations in OT neurons, and intracerebral as well as peripheral release of OT. We further provide evidence for the efficiency of chemogenetic manipulation at behavioral levels, demonstrating that evoked activation of OT neurons leads to social motivation and anxiolysis. Altogether, our results will be profitable for researchers working on the physiology of neuroendocrine systems, peptidergic modulation of behaviors and translational psychiatry. [ABSTRACT FROM AUTHOR]

• A novel water mist generator for controlling underground coal fires was developed. • Effects of structural and operational parameters on atomization were investigated. • Fire suppression effects were assessed by both laboratory and field experiments. Coal fires represent a worldwide hazard, and water mist is used as an effective means in controlling the fires. In the present study a new self-suctioning water mist generator was developed that produces efficient atomization at a relatively low pressure without the need for compressed air and improving the applicability of water mist systems in coal fire areas. The effects of structural parameters of the generator and operational variable (water supply pressure) on atomization performance were investigated. Both laboratory experiments and field tests were conducted to assess the fire suppression efficiency and cooling effects of this generator. The results show that the generator can attain a high degree of atomization after the optimization on the structural parameters and operational variable. The water mist produced by this device was also demonstrated to effectively suppress coal combustion. Compared with traditional water injection techniques, this new approach created more temperature decrease during a same period of application time while consuming an equal amount of water. This work therefore provides a practicable technique for the effective control of underground coal fires. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Polypyrrole mediated Z-scheme photocatalytic system g-C 3 N 4 /PPy/Bi 2 WO 6 is successfully fabricated. • PPy serves as a charge transmission bridge between the g-C 3 N 4 and the Bi 2 WO 6. • The as-prepared g-C 3 N 4 /PPy/Bi 2 WO 6 composites possess high electron-hole separation efficiency. Abstract An all-solid-state Z-scheme photocatalytic system g-C 3 N 4 /PPy/Bi 2 WO 6 (GPB) is successfully fabricated by introducing both polypyrrole (PPy) and graphitic carbon nitride (g-C 3 N 4) nanoparticles on the surface of Bi 2 WO 6 microflowers. PPy, as a kind of conductive polymers, can be regarded as the Ohmic contact in Z-scheme systems. Furthermore, PPy serves as a charge transmission bridge between the g-C 3 N 4 and the Bi 2 WO 6. The g-C 3 N 4 /PPy/Bi 2 WO 6 sample with the PPy amount of 0.5 wt% (GPB-0.5) exhibits enhanced visible-light absorption and high electron-hole separation efficiency. It can remove 98.0% of RhB within 100 min, the photocatalytic activity of which is higher than that of other control samples. Both photoelectrochemical test and scavenging experiment identify that h + and ⋅ O 2 − are the main active species in the photocatalysis process. Our work could offer a new sight to design and fabricate photocatalyst with excellent utilization efficiency of solar energy. [ABSTRACT FROM AUTHOR]

Highlights • Moiré fringe is used for proximity lithography. • Complex mark consists of coarse and final alignment marks. • Coarse and final alignment marks are distinguished in frequency spectrum. • Alignment shows nanoscale precision in hundreds of microns range. Abstract We propose a novel alignment method with nanoscale precision and hundreds of microns detecting range for proximity lithography. With this method, both coarse and final alignments are realized by complex grating based on moiré fringe. For distinguishing the complex gratings in frequency spectrum, there is no interference between the coarse and the final alignment parts. Within only one pattern, modulation of the coarse mark and phase of the final mark can be calculated respectively. Combining the two results, we can do the alignment with nanoscale precision in large measurement range. Furthermore, the structure of our measurement system is simple. Simulation and experiments are carried out to validate the feasibility of the proposed method. [ABSTRACT FROM AUTHOR]

Abstract Phytoremediation with aquatic macrophyte has been considered as an eco-friendly technique for controlling harmful cyanobacteria outbreak and proven to be effective. The conventional water quality parameters are frequently measured to evaluate the effectiveness of phytoremediation. However, the concentration of microcystin-leucine-arginine (MC-LR) in different vegetated water still remains uncertain. In this study, the contents of MC-LR in four macrophyte-vegetated lagoons were determined by solid phase extraction and ultra-high-performance liquid chromatography with tandem mass spectrometry technology. Results indicated that MC-LR was found in Nymphaea tetragona lagoon (lagoon-S), Vallisneria spiralis lagoon (lagoon-B) and another Vallisneria spiralis lagoon (lagoon-J). Only in lagoon dominated by Pistia stratiotes L. (lagoon-D), MC-LR concentration was undiscovered regardless of seasonal variation. The levels of MC-LR varied seasonally and were affected by the different vegetated aquatic macrophytes. The results suggest that in addition to conventional physicochemical parameters and indicators of water quality, MC-LR levels should be taken into consideration when the effectiveness of phytoremediation is assessed. Graphical abstract Image 1 Highlights • Eliminating the matrix effects on MC-LR detection occurred in vegetated water environment. • MC-LR concentrations in studied lagoons showed seasonal variation. • Nymphaea tetragona and Pistia stratiotes L. are inclined to inhibit MC-LR releases. • The different vegetated macrophytes and epiphytic materials affected the levels of MC-LR. [ABSTRACT FROM AUTHOR]

MLL-rearranged leukemia is an aggressive malignancy associated with poor outcome, which is refractory to conventional treatment. Melatonin has been proven to exert anti-tumor activity, but the effect of melatonin on MLL-r leukemia and the underlying mechanism remain poorly understood. In this study, melatonin inhibited cell proliferation and induced apoptosis by activating the caspase-dependent apoptotic pathway in MLL-r leukemia cells. Mechanistic investigations revealed that melatonin suppressed the expression of hTERT by abrogating the binding activity of RBFOX3 to the hTERT promoter. Melatonin also blocked NF-κB nuclear translocation and suppressed NF-κB binding to the COX-2 promoter, thereby suppressing the expression of COX-2. In addition, clinical samples revealed that melatonin exerts anti-leukemic activity in primary MLL-r leukemia blasts ex vivo. In vivo, the mice treated with melatonin experienced a larger reduction in leukemic burden than the control group in a MLL-r leukemia xenograft mouse model. Collectively, these results suggest that melatonin inhibits MLL-rearranged leukemia through suppressing the RBFOX3/hTERT and NF-κB/COX-2 signaling pathways. Our findings provide new insights into the role of melatonin for MLL-r leukemia treatment. [ABSTRACT FROM AUTHOR]

Abstract A series of resveratrol dimer derivatives against Alzheimer's disease (AD) was obtained by structural modification and transformation using resveratrol as substrate. Biological analysis revealed that these derivatives had moderate inhibitory activity against human monoamine oxidase B (h MAO-B). In particular, 3 and 7 showed the better inhibitory activity for h MAO-B (IC 50 = 3.91 ± 0.23 μ M, 0.90 ± 0.01 μ M) respectively. Compound 3 (IC 50 = 46.95 ± 0.21 μ M for DPPH, 1.43 and 1.74 trolox equivalent by ABTS and FRAP method respectively), and 7 (IC 50 = 35.33 ± 0.15 μ M for DPPH, 1.70 and 1.97 trolox equivalent by ABTS method and FRAP method respectively) have excellent antioxidant effects. Cellular assay shown that 3 and 7 had lower toxicity and were resistant to neurotoxicity induced by oxidative toxins (H 2 O 2 , rotenone and oligomycin-A). More importantly, the selected compounds have neuroprotective effects against ROS generation, H 2 O 2 -induced apoptosis and a significant in vitro anti-inflammatory activity. The results of the parallel artificial membrane permeability assay for blood-brain barrier indicated that 3 and 7 would be predominant to cross the blood-brain barrier. In this study, mouse microglia BV2 cells were used to establish cell oxidative stress injury model with H 2 O 2 and to explore the protective effect and mechanism of 3 and 7. In general, 3 and 7 can be considered candidates for potential treatment of AD. Graphical abstract Image 1 Highlights • A series of resveratrol dimer derivatives against Alzheimer's disease (AD) was obtained by structural modification and transformation using resveratrol as substrate. • Most of the compounds showed moderate to good inhibitory activities against MAO-B as well as remarkable antioxidant activities. • Compounds 3 and 7 displayed a balanced multifunctional profile having MAO-B inhibition, excellent antioxidant activity. • Compounds 3 and 7 possessed significant neuroprotection against H2O2-induced oxidative damage on PC12 cells and BV2 microglial cells and Lipopolysaccharides (LPS)-stimulated inflammation on BV2 microglial cells. • Compounds 3 and 7 have lower toxicity and could cross the blood-brain barrier. [ABSTRACT FROM AUTHOR]

Abstract Layered double hydroxides (LDHs) have great potential as protective coatings on magnesium alloys due to their nanolamellar structure and exchangeability of interlayer anions. ZnAl layered double hydroxides films intercalated with nitrate anions (ZnAl-NO 3 −-LDHs) was synthesized on the AZ31 magnesium alloy by hydrothermal method. In order to obtain better corrosion resistance, ZnAl-X-LDHs (X = Cl−, VO 4 3−, PO 4 3−, or MoO 4 2−) were prepared by using ZnAl-NO 3 −-LDHs as a precursor, and Cl−, VO 4 3−, PO 4 3−, and MoO 4 2− anions intercalated into the LDHs interlayers to replace NO 3 − through anion-exchange reaction. X-ray diffraction (XRD), scanning electronic microscopy (SEM) and Fourier transform infrared (FT-IR) spectroscopy were used to investigate structure, morphology and composition of the ZnAl-LDHs. The corrosion resistance of ZnAl-LDHs intercalated with different anions was compared by potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) measurements. The results show that the corrosion resistance of ZnAl-LDHs films is ranged in order as follows: ZnAl-VO 4 3−-LDHs > ZnAl-MoO 4 2−-LDHs > ZnAl-PO 4 3−LDHs > ZnAl-Cl−LDHs > ZnAl-NO 3 −LDHs. ZnAl-VO 4 3−-LDHs has the largest basal spacing distances d (003) value and strongest ability to release anions and absorb chloride ions, so ZnAl-VO 4 3−-LDHs films has the optimal corrosion resistance and can provide enhanced anticorrosion protection for magnesium alloys substrate. Graphical abstract Unlabelled Image Highlights • ZnAl-LDHs intercalated with Cl−, PO 4 3−, MoO 4 2− and VO 4 3− anions were synthesized successfully by anion exchange reaction. • The anti-corrosion of ZnAl-LDHs with different anions: VO 4 3−>MoO 4 2−>PO 4 3−>Cl->NO 3 −. • The ZnAl-VO 4 3−-LDHs have the best anion-exchange ability. [ABSTRACT FROM AUTHOR]

Highlights • We identified abnormal whole-brain connectivity in mild-moderate Parkinson's Disease. • Our study identified Parkinson's Disease patients from controls with 80.28% accuracy. • We revealed abnormal lateralization of brain connectivity in mild-moderate patients. Abstract Objective Our study aims to extract significant disorder-associated patterns from whole brain functional connectivity to distinguish mild-moderate Parkinson's disease (PD) patients from controls. Methods Resting-state fMRI data were measured from thirty-six PD individuals and thirty-five healthy controls. Multivariate pattern analysis was applied to investigate whole-brain functional connectivity patterns in individuals with 'mild-moderate' PD. Additionally, the relationship between the asymmetry of functional connectivity and the side of the initial symptoms was also analyzed. Results In a leave-one-out cross-validation, we got the generalization rate of 80.28% for distinguishing PD patients from controls. The most discriminative functional connectivity was found in cortical networks that included the default mode, sensorimotor and attention networks. Compared to patients with the left side initially affected, an increased abnormal functional connectivity was found in patients in whom the right side was initially affected. Conclusions Our results indicated that discriminative functional connectivity is likely associated with disturbances of cortical networks involved in sensorimotor control and attention. The spatiotemporal patterns of motor asymmetry may be related to the lateralized dysfunction on the early stages of PD. Significance This study identifies discriminative functional connectivity that is associated with disturbances of cortical networks. Our results demonstrated new evidence regarding the functional brain changes related to the unilateral motor symptoms of early PD. [ABSTRACT FROM AUTHOR]

The recent rapid evolution of PRRSVs has resulted in certain biological characteristic changes, such as the fact that an increasing number of field PRRSVs can be isolated from PAMs but not from Marc-145 cells. In this study, we first isolated Marc-145-unadaptive field PRRSV strains from PAMs; sequence analysis showed that these PRRSVs belong to the HP-PRRSV (lineage 8) branch or NADC30-Like (lineage 1) branch. We further found major variations in ORF2-4 regions. To explore the viral adaptation mechanisms in detail, we constructed a full-length cDNA clone of MY-376, a Marc-145-unadaptive PRRSV. Construction of serially chimeric viruses of HuN4-F112 (a Marc-145-adaptive strain) and MY-376 demonstrated that variation in the minor envelope protein (GP2a and GP3) complex is a main determinant of PRRSV tropism for Marc-145 cells. [ABSTRACT FROM AUTHOR]

Double perovskites A 2 CuSbX 6 (A = Cs, Rb, K; X = Cl, Br, I) have been investigated by first principles calculations. According to the tolerance factor, formation energy, binding energy and elastic stability criterion, the other materials except Cs 2 CuSbI 6 can be judged to have mechanical and thermodynamic stability. All the materials are ductile and show potential in wearable devices. The perovskites possess indirect band structures with bandgaps as 1.163 eV, 0.850 eV, 0.305 eV, 1.140 eV and 1.123 eV for Cs 2 CuSbCl 6 , Cs 2 CuSbBr 6 , Cs 2 CuSbI 6 , Rb 2 CuSbCl 6 and K 2 CuSbCl 6 , respectively. Compared with the other two Cl-based perovskites, K 2 CuSbCl 6 exhibits better optoeletronic properties because of its smaller average effective mass(0.294 m 0 for m h ∗ and 0.201 m 0 for m e ∗), longer carrier lifetime and higher light absorption coefficient (6.58 × 104 cm−1) in visible region. In addition, K 2 CuSbCl 6 has a high Debye temperature which represents better stability. The results indicate that K 2 CuSbCl 6 is an excellent candidate for photovoltaic and optoeletronic devices. [ABSTRACT FROM AUTHOR]

• Sub lethal propionate allowed growth while suppressed virulence of B. cinerea. • Propionate activated methylcitrate cycle to attenuate infection cushion formation. • Propionate down regulated the genes related to the functions of infection cushion. • Multiple transcriptome data deciphered regulation mechanisms of fungal virulence. Botrytis cinerea is a devastating pathogen causing gray mold in fruits and vegetables if not properly managed. Although the mechanisms remain unclear, we previously revealed that the safe food additive calcium propionate (CP) could suppress gray mold development on grapes. The present study reports that sub-lethal dose of CP (0.2 % w/v) could allow growth with substantial reprograming the genome-wide transcripts of B. cinerea. Upon CP treatment, the genes related to fungal methylcitrate cycle (responsible for catabolizing propionate) were upregulated. Meanwhile, CP treatment broadly downregulated the transcript levels of the virulence factors. Further comparative analysis of multiple transcriptomes confirmed that the CP treatment largely suppressed the expression of genes related to development and function of infection cushion. Collectively, these findings indicate that CP can not only reduce fungal growth, but also abrogate fungal virulence factors. Thus, CP has significant potential for the control of gray mold in fruit crops. [ABSTRACT FROM AUTHOR]

• Activating multiple deformation modes can improve the formability of Mg-RE alloy. • Slip order at room temperature meets basal slips → pyramidal slips → prismatic slips. • CDMN could achieve high accumulative deformation at room temperature. Particular lattice structure restrains the plastic formability of Mg alloy, and thus an effective approach is needed to conquer this bottleneck. This short communication presents that a thin sheet with 0.26 mm thickness of Mg rare earth alloy was prepared by rolling with 97.4% total reduction at room temperature. A deformation mode of continually dynamic micro-nanocrystallization (CDMN) dominated the plastic deformation process in which an extreme grain refinement could be observed. This work hopefully introduces a novel perspective to the plastic deformation field of Mg alloy. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the leading cause of death globally and poses at significant challenge in terms of effective medical treatment. Leonurus japonicus Houtt , a traditional Chinese herb, is widely used in China for the treatment of obstetrical and gynecological disorders, including menstrual disorders, dysmenorrhea, amenorrhea, blood stasis, postpartum bleeding, and blood-related diseases such as CVD. Stachydrine, the main alkaloid component of Leonurus, has been shown to exhibit a wide range of biological activities including anti-inflammatory, antioxidant, anti-coagulant, anti-apoptotic, vasodilator, angiogenic promoter. Additionally, it has been demonstrated to have unique advantages in the prevention and treatment of CVD through regulation of various disease-related signaling pathways and molecular targets. In this comprehensive review, we examine the latest pharmacological effects and molecular mechanisms of Stachydrine in treating cardiovascular and cerebrovascular diseases. Our aim is to solid scientific basis for the development of new CVD drug formulations. [Display omitted] • 1 STA can protect vascular endothelial cells from damage. • 2 STA can help to prevent cardiovascular disease (CVD) by inhibiting cardiomyocyte hypertrophy, cardiomyocyte fibrosis, and anti-apoptosis. • 3 STA can also protect Central Nervous System (CNS) diseases, such as protect traumatic brain injury and Alzheimer's disease. • 4 STA has properties of good bioavailability, non-toxic and very low toxicity. [ABSTRACT FROM AUTHOR]

• Differentiation of DL-Glu and DL-Glu·H 2 O by terahertz spectroscopy. • Characterization of the dehydration process of DL-glutamic acid monohydrate and validation of the results. • Data will be made available on request. • The inter- and intramolecular hydrogen bonding of DL-Glu and DL-Glu·H 2 O was analyzed. The dehydration process involves the dissociation and reorganization of hydrogen bonds, and for the characterization of the dehydration process of amino acid-based hydrates, the analysis of their molecular vibrational modes and hydrogen bonds is still challenging nowadays. In this paper, the dynamic process of the dehydration of DL-glutamic acid monohydrate was monitored using terahertz spectroscopy. Quantitative simulations were performed on DL-glutamic acid and its monohydrate, with vibrational mode assignments and hydrogen bonding network analysis based on Density Functional Theory (DFT) for terahertz absorption peaks. The results show that the hydrogen bond stretching vibration is intermixed with atomic vibration. Specifically, the intermolecular hydrogen bond O 4 -H 9 ···O 2 of DL-glutamic acid exhibits a stronger vibration at 2.43 THz. Furthermore, the intramolecular hydrogen bond O 5 -H 11 ···O 4 in DL-glutamic acid monohydrate shows significant changes in bond length and bond angle at 1.85 THz. These findings validate the effectiveness of terahertz spectroscopy in monitoring the transformation process of the hydrate and the analysis of the hydrogen bond. [Display omitted] [ABSTRACT FROM AUTHOR]

Disease represents a specific case of malfunctioning within a complex system. Whereas it is often feasible to observe and possibly treat the symptoms of a disease, it is much more challenging to identify and characterize its molecular root causes. Even in infectious diseases that are caused by a known parasite, it is often impossible to pinpoint exactly which molecular profiles of components or processes are directly or indirectly altered. However, a deep understanding of such profiles is a prerequisite for rational, efficacious treatments. Modern omics methodologies are permitting large-scale scans of some molecular profiles, but these scans often yield results that are not intuitive and difficult to interpret. For instance, the comparison of healthy and diseased transcriptome profiles may point to certain sets of involved genes, but a host of post-transcriptional processes and regulatory mechanisms renders predictions regarding metabolic or physiological consequences of the observed changes in gene expression unreliable. Here we present proof of concept that dynamic models of metabolic pathway systems may offer a tool for interpreting transcriptomic profiles measured during disease. We illustrate this strategy with the interpretation of expression data of genes coding for enzymes associated with purine metabolism. These data were obtained during infections of rhesus macaques ( Macaca mulatta ) with the malaria parasite Plasmodium cynomolgi or P. coatneyi . The model-based interpretation reveals clear patterns of flux redistribution within the purine pathway that are consistent between the two malaria pathogens and are even reflected in data from humans infected with P. falciparum . This article is part of a Special Issue entitled: Accelerating Precision Medicine through Genetic and Genomic Big Data Analysis edited by Yudong Cai & Tao Huang. [ABSTRACT FROM AUTHOR]

Silver nanowires (Ag NWs) network is considered a promising alternative to replace indium tin oxide (ITO) as transparent conductive electrode (TCE). However, there are several intrinsic shortcomings such as rough surface topography, poor ambient and thermal stability still restrict their practical application. Here, we demonstrated a low temperature solution-processed composite TCE comprising of Ag NWs and ZnO nanoparticles (NPs) could resolve above issues. The highest temperature in whole process is no more than 100 °C. By optimizing the density of Ag NWs together with the thickness of ZnO NPs layer, the composite TCE showed excellent flexibility, ambient and thermal stability (∼300 °C) as well as high electrical conductivity (∼20 Ω/sq) and good optical transparency (∼87% at 550 nm). In addition, the ZnO NPs capping layer reduced the surface roughness of Ag NWs network by more than half of its initial value. All the demonstrated properties show the Ag NWs/ZnO composite TCE would be an ideal choice in a variety of flexible optoelectronic devices. [ABSTRACT FROM AUTHOR]

Objective Hepatocellular carcinoma (HCC) is one of the most lethal human malignancies in China, and the genetic link of hepatocarcinogenesis remains to be defined. Thus, we explored the role of SET and myeloid translocation protein 8, Nervy, and DEAF1 (MYND) domain containing protein 3 ( SMYD3 ) gene polymorphism on risk and prognosis of HCC. Methods A total of 236 patients with HCC who received treatment in Affiliated Hospital of Jining Medical University for the first time and 230 healthy individuals were enrolled in the study. After DNA extraction for all the subjects, polymerase chain reaction (PCR) was used to amplify and sequence variable numbers of tandem repeat (VNTR) loci of SMYD3 gene. SMYD3 gene was genotyped and its frequency distribution was calculated. Age, education level, income, smoking and drinking history, HCC family history, tumor node metastasis (TNM) staging, maximum tumor diameter, lymph node metastasis (LNM) etc. were investigated. Correlation of SMYD3 gene polymorphism and other risk factors with the occurrence and prognosis of HCC was analyzed. Results The family history of HCC, drinking history, cirrhosis, and HBV or/and HCV infection, SMYD3 VNTR 3/3 were more frequently observed in subjects with HCC. Patients with SMYD3 VNTR 3/3 genotype, drinking-history, family history of HCC, cirrhosis and hepatitis B virus (HBV), TNM staging, maximum tumor diameter, LNM were more vulnerable to HCC. Besides, patients with SMYD3 VNTR 3/3 genotype had lower 2- and 3-year survival rate. The COX regression analysis revealed that drinking history, family history of HCC, SMYD3 VNTR 3/3 genotype, TNM staging, and LNM were all related to the prognosis of HCC. Conclusion This study indicates that drinking history, family history of HCC and SMYD3 VNTR 3/3, TNM staging, maximum tumor diameter, LNM might be risk factors for HCC, and SMYD3 VNTR 3/3 might contribute to a lower 2- and 3-year survival rate of patients with HCC. [ABSTRACT FROM AUTHOR]

Community detection is one of important issues in the research of complex networks. In literatures, many methods have been proposed to detect community structures in the networks, while they also have the scope of application themselves. In this paper, we investigate an important measure for community detection, Surprise (Aldecoa and Marín, Sci. Rep. 3 (2013) 1060), by focusing on the critical points in the merging and splitting of communities. We firstly analyze the critical behavior of Surprise and give the phase diagrams in community-partition transition. The results show that the critical number of communities for Surprise has a super-exponential increase with the increase of the link-density difference, while it is close to that of Modularity for small difference between inter- and intra-community link densities. By directly optimizing Surprise, we experimentally test the results on various networks, following a series of comparisons with other classical methods, and further find that the heterogeneity of networks could quicken the splitting of communities. On the whole, the results show that Surprise tends to split communities due to various reasons such as the heterogeneity in link density, degree and community size, and it thus exhibits higher resolution than other methods, e.g., Modularity, in community detection. Finally, we provide several approaches for enhancing Surprise. [ABSTRACT FROM AUTHOR]

In this study, a thin-walled polyhedral polymer pipe liner is proposed for the internal rehabilitation of a deteriorated/cracked underground circular metal pipe. The pipe liner is externally confined and subjected to the hydrostatic pressure of water seeped through the cracked pipe. The critical buckling pressure of the pipe liner is derived analytically based on the principle of minimum potential energy and compared with that of a cylindrical pipe liner. A finite element model of the pipe liner is established and analyzed to understand pressure-deformation equilibrium paths and the stability of post-buckling behavior. The analytical buckling pressure is in excellent agreement with the numerical results. The buckling pressure of a polyhedral liner increases with the increase of thickness-to-radius ratio and the decrease of the number of sides in polygon base shape. In comparison with the cylindrical liner, the polyhedral liner can increase buckling pressure up to 10 times but result in a less stable post-buckling behavior. [ABSTRACT FROM AUTHOR]

A non-intrusive method is introduced to predict binaural speech intelligibility in noise directly from signals captured using a pair of microphones. The approach combines signal processing techniques in blind source separation and localisation, with an intrusive objective intelligibility measure (OIM). Therefore, unlike classic intrusive OIMs, this method does not require a clean reference speech signal and knowing the location of the sources to operate. The proposed approach is able to estimate intelligibility in stationary and fluctuating noises, when the noise masker is presented as a point or diffused source, and is spatially separated from the target speech source on a horizontal plane. The performance of the proposed method was evaluated in two rooms. When predicting subjective intelligibility measured as word recognition rate, this method showed reasonable predictive accuracy with correlation coefficients above 0.82, which is comparable to that of a reference intrusive OIM in most of the conditions. The proposed approach offers a solution for fast binaural intelligibility prediction, and therefore has practical potential to be deployed in situations where on-site speech intelligibility is a concern. [ABSTRACT FROM AUTHOR]

The Mg-Li alloy bars with density of 1.38 g/cm 3 as well as ultimate tensile strength of 329.2 MPa were fabricated. Simultaneously, an industrial process with convenience and low cost was developed. In the cast alloys, hcp-Mg was transformed gradually into bcc-Li with increasing Li content. During extruding at different temperatures, the dynamic recrystallization (DRX) in Mg-8Li-5Al-2Zn-0.5Y was weaker than Mg-5Li-5Al-2Zn-0.5Y and Mg-11.4Li-5Al-2Zn-0.5Y due to the mutual limitation between hcp-Mg (α) and bcc-Li (β). In the annealing process, abnormal grain growth in Mg-11.4Li-5Al-2Zn-0.5Y was found at 573 K, and a kind of regular dendritic structure was discovered in the coarse grains at 593 K. Additionally, a sort of solid solution strengthening behavior in bcc-Li was observed and enhanced remarkably the alloy strength (increased by ～160 MPa in maximum). Through controlling cooling velocity, a precipitation behavior could be achieved in the alloys. Through mathematical modeling with high accuracy, the relationships among microstructural evolution and alloy properties in the solid solution and precipitation processes were quantitatively analyzed and determined. [ABSTRACT FROM AUTHOR]

The microstructural evolution and mechanical properties of Mg-xLi-3Al-2Zn-0.2Y (x = 5, 8 and 11) alloys under the different rolling temperatures and annealing routes were investigated. The results showed that the Li addition transformed gradually the Mg crystal structure from hcp to bcc. With ascending rolling temperature, the Mg-11Li-3Al-2Zn-0.2Y (LAZ1132-0.2Y) alloy achieved the dynamic recrystallization behavior in advance, as compared with Mg-5Li-3Al-2Zn-0.2Y (LAZ532-0.2Y) and Mg-8Li-3Al-2Zn-0.2Y (LAZ832-0.2Y). Moreover, {0002} basal texture in LAZ532-0.2Y was weakened gradually by ascending rolling temperature. In LAZ832-0.2Y, {11−20} texture component relatively kept stable when the {0002} basal texture was weakened. When rolling at 503 K, a new {211} <201> texture was observed in LAZ1132-0.2Y. In the annealing process, a kind of abnormal grain growth took place in LAZ1132-0.2Y. In addition, a strengthening behavior could be accomplished by strengthening β matrix (bcc). [ABSTRACT FROM AUTHOR]

The Zoige depression is an important depocenter within the northeast Songpan-Ganzi flysch basin, which is bounded by the South China, North China and Qiangtang Blocks and forms the northeastern margin of the Tibetan Plateau. This paper discusses the sediment provenance and Mesozoic-Cenozoic evolution of the Zoige depression in the Songpan-Ganzi flysch basin, eastern Tibetan Plateau, using the detrital zircon U-Pb ages and apatite fission-track data from the Middle to Late Triassic sedimentary rocks in the area. The U–Pb ages of the Middle to Late Triassic zircons range from 260–280 Ma, 429–480 Ma, 792–974 Ma and 1800–2500 Ma and represent distinct source region. Our new results demonstrate that the detritus deposited during the Middle Triassic (Ladinian, T 2 zg) primarily originated from the Eastern Kunlun and North Qinling Orogens, with lesser contributions from the North China Block. By the Late Triassic (early Carnian, T 3 z), the materials at the southern margin of the North China Block were generally transported westward to the basin along a river network that flowed through the Qinling region between the North China and South China Blocks: this interpretation is supported by the predominance of the bimodal distribution of 1.8 Ga and 2.5 Ga age peaks and a lack of significant Neoproterozoic zircon. Since the Late Triassic (middle Carnian, T 3 zh), considerable changes have occurred in the source terranes, such as the cessation of the Eastern Kunlun Orogen and North China Block sources and the rise of the northwestern margin of the Yangtze Block and South Qinling Orogen. These drastic changes are compatible with a model of a sustained westward collision between the South China and North China Blocks during the late Triassic and the clockwise rotation of the South China Block progressively closed the basin. Subsequently, orogeny-associated folds have formed in the basin since the Late Triassic (late Carnian), and the study area was generally subjected to uplifting and cooling stages during 200–160 Ma, 90–120 Ma, 20–40 Ma and 10 Ma as evidenced by the apatite fission track data and the thermal history modeling. According to the regional background, we conclude that these stages are as follows, from oldest to youngest: the E-W extrusion across the entire Chinese mainland at the beginning of the Yanshanian period (200–160 Ma), the interaction among the North China, Yangtze and India plates during the Late Jurassic-Early Cretaceous, the collision between the Indian and Eurasian plates since the Paleogene, and the rapid uplift simultaneous with the formation of the Tibetan Plateau since 10 Ma. [ABSTRACT FROM AUTHOR]

Microstructural evolution, textural development and strengthening mechanism of α, α+β and β structure Mg-Li alloys during extruding and annealing process were investigated. It showed that, with increasing Li content, the α-Mg matrix was transformed gradually to the β-Li matrix. In the three alloys, for α-Mg structure, the c-axis of close-packed plane of α-Mg was inclined perpendicular to the extrusion direction after extruding. However, for β-Li structure, the c-axis of close-packed plane of β-Li was inclined parallel to the extrusion direction after extruding. During annealing, a new predominance of {11−20} recrystallization texture was observed in α-Mg matrix. However, no recrystallization texture was achieved in β-Li matrix. Additionally, a solid solution strengthening during annealing could be observed apparently in the β-Li matrix. To study and quantify the strengthening behavior, the relationship models between ultimate tensile strength (UTS), yield strength (YS), hardness (HV) and AlLi volume fraction (VF) were defined using mathematical modeling and regression analysis. It showed that the effect of VF on UTS was much more than that of others. In LAZ832-0.2Y, the fitting models for UTS on VF and UTS on YS revealed the relationship of quadratic function. However, in LAZ1132-0.2Y, the fitting models for them exhibited the linear relationship. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL) is characterized by the accumulation of abnormal lymphoblasts in the bone marrow and blood. Though great progress has been made for improvement in clinical treatment during the past decades, some children with ALL still relapsed. Glucocorticoid (GC) resistance is an important clinical problem for ALL treatment failure. Therefore, further understanding of the mechanism of GC resistance and exploring novel therapeutic strategies are crucial for improving treatment outcome. The reported involvement of microRNAs (miRNAs) in drug resistance implied that deregulated miRNA expression might contribute to GC treatment response of ALL. However, individual miRNAs and their functional mechanisms potentially involved in the GC response are still largely unknown. In the present study, we found that miR-124 was up-regulated in prednisone insensitive human ALL cell line and prednisone-poor response ALL patients. Furthermore, it was found that miR-124 might contribute to GC resistance by promoting proliferation and inhibiting apoptosis of ALL cells. Importantly, we validated that miR-124, targeted and decreased the expression of glucocorticoid receptor (NR3C1), prevented the inhibitory effect of GC in ALL. These findings strongly suggest that miR-124 is critical in poor GC response and may serve as a potential therapeutic target in ALL with poor GC resistance. [ABSTRACT FROM AUTHOR]

Dimensional metrology for micro structure plays an important role in addressing quality issues and observing the performance of micro-fabricated products. In white light interferometry, the proposed method is expected to measure three-dimensional topography through modulation depth in spatial frequency domain. A normalized modulation depth is first obtained in the xy plane (image plane) for each CCD image individually. After that, the modulation depth of each pixel is analyzed along the scanning direction (z-axis) to reshape the topography of micro samples. Owing to the characteristics of modulation depth in broadband light interferometry, the method could effectively suppress the negative influences caused by light fluctuations and external irradiance disturbance. Both theory and experiments are elaborated in detail to verify that the modulation depth-based method can greatly level up the stability and sensitivity with satisfied precision in the measurement system. This technique can achieve an improved robustness in a complex measurement environment with the potential to be applied in online topography measurement such as chemistry and medical domains. [ABSTRACT FROM AUTHOR]

The growth performance, flavor substances, mouthfeel characteristics and collagen synthesis in the muscle of sub-adult grass carp (659.07 ± 0.74 g) were investigated after 60-day feeding with graded dietary levels of lysine (6.0–17.0 g/kg diet). The results showed that optimal dietary lysine levels boosted the growth of grass carp. Proper dietary lysine levels improved muscle inosine monophosphate, free amino acids, unsaturated fatty acid content, water holding capacity, pH and shear force (hardness). The diets also decreased lactate content, and enhanced collagen content by increasing transcription, translation and post-translational modifications of type I collagen, probably via activating TGF-β1/Smads and PI3K/Akt/p70S6k/la ribonucleoprotein domain family member 6 (LARP6) signaling; this enhanced prolyl 4-hydroxylase (P4H) and lysyl hydroxylase (LOX) content, thereby improving the flavor and mouthfeel of muscle. In summary, this research indicated that dietary lysine could lead to the enhancement of muscle flavor substances, mouthfeel characteristics and type I collagen synthesis in sub-adult grass carp. Based on the PWG and shear force, the dietary requirements of lysine for sub-adult grass carp are 13.43 and 12.96 g/kg, respectively. • Lysine increased muscle aspartic acid and glutamic acid, nucleotide (IMP), fatty acid contents. • Lysine increased the mouthfeel of fish muscle by increasing WHC, pH and hardness. • Lysine improved muscle collagen content probably by regulating TGF-β1/Smads, LARP6, P4H content and LOX activity in grass carp. • Lysine promoted the growth of grass carp. [ABSTRACT FROM AUTHOR]

• A novel coaxial focus position detection technique based on differential modulation evaluation is proposed for improving focus position detection accuracy. • The proposed method can eliminate the influence of different reflectivity of the surface of the substrate. • Through experimentally verified, the focus detection accuracy is better than 5nm in the case of an objective lens with a numerical aperture of 0.9. In laser direct lithography, coaxial focus position detection techniques are needed to ensure the manufacturing accuracy. The existing coaxial focus position detection techniques include pinhole method, critical angle method, Foucault knife-edge method and astigmatism method, which are susceptible to the intensity fluctuation and have high requirement for the installation and adjustment of the system. Furthermore, the resolution of existing method is generally between 10-20nm. We proposed a novel coaxial focus position detection technique based on differential modulation evaluation. In this study, the imaging space of the lithography lens is coded by grating pattern. And a differential detection system is used to get the substrate height from the image modulated by the lens focus depth. Moreover, this proposed method can eliminate the influence of different reflectivity of the surface of the substrate. Furthermore, the focus detection accuracy is better than 5nm in the case of an objective lens with a numerical aperture of 0.9. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD) is a chronic, progressive, and degenerative neurological disorder that is characterized by the degeneration of dopamine neurons in the substantia nigra and the formation of intracellular Lewy inclusion bodies. Resting-state functional magnetic resonance imaging (RS-fMRI) has demonstrated evidence of changes in metabolic patterns in individuals with PD. The purpose of this study was to determine whether the presence of PD could be “predicted” based on resting fluctuations in the blood oxygenation level dependent signal. We utilized RS-fMRI to measure the amplitude of low-frequency fluctuation (ALFF) and the fractional ALFF (fALFF) in 51 patients with PD and 50 age- and sex-matched healthy controls. Compared with the healthy controls, the individuals with PD exhibited altered ALFFs in the bilateral lingual gyrus and left putamen and an altered fALFF in the right cerebellum posterior lobe. Support vector machines (SVMs), which comprise a supervised pattern recognition method that enables predictions at the individual level, were trained to separate individuals with PD from healthy controls based on the ALFF and fALFF. Using the leave-one-out cross-validation method to analyze our sample, we reliably distinguished the participants with PD from the controls with 92% sensitivity and 87% specificity. Overall, these findings suggest that the SVM-neuroimaging approach may be of particular clinical value because it enables the accurate identification of PD at the individual level. RS-fMRI should be considered for development as a biomarker and an analytical tool for the evaluation of PD. [ABSTRACT FROM AUTHOR]

The microstructural evolution and mechanical properties of α phase and α+β phase and β phase Mg-Li wrought alloys after heat treatment were investigated. The results showed that, in extruded Mg-5Li-3Al-2Zn-0.2Y, no precipitation was observed in the range of 220–320 °C for 12 h. In the extruded Mg-8Li-3Al-2Zn-0.2Y and Mg-11Li-3Al-2Zn-0.2Y alloys, a precipitation behavior was occurred in β phase after heat treatment. However, in the extruded Mg-11Li-3Al-0.2Y and Mg-11Li-3Al-0.2Ce alloys, there existed a transformation between the precipitation and the solid solution in β phase. In addition, the mechanical properties of the alloys were influenced remarkably by the precipitation and solid solution. [ABSTRACT FROM AUTHOR]