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In this paper, we study the forward and the inverse problem for the fractional magnetic Schrödinger equation with a nonlinear electric potential. We first obtain the maximum principle for the linearized equation and apply it to show that the problem is well-posed under suitable assumptions for the exterior condition. Then we obtain the uniqueness in recovering both the magnetic and the nonlinear electric potentials, assumed to be analytic in terms of the solution, from the exterior data of the solution. [ABSTRACT FROM AUTHOR]

Prenylated resveratrols are drug candidates presented in many natural sources. They possess multiple pharmacological activities. Due to the limited abundance in nature and disadvantage of chemical synthesis, it is required to produce prenylated resveratrols by biological strategy. In this work, a prenyltransferase iacE from Pestalotiopsis fici was prepared by heterologous overexpression. It could catalyze 2- C -prenylation of resveratrol efficiently. Dimethylallyl diphosphate (DMAPP) and geranyl diphosphate (GPP) could serve as prenyl donor. Glu97, Thr114 and Tyr413 were proved to be important residues in the active site by site-directed mutagenesis. The product was purified and identified to be 2- C -prenyl resveratrol by NMR. 2- C -prenyl resveratrol exerted neuroprotective activity through inhibiting ROS overproduction and improving the activities of antioxidant enzymes in HT22 cell. The genes involved in antioxidant defense were regulated, including upregulated CAT , SOD2 , NFE2L2 , GPx4 , and downregulated PTGS2 and ACSL4. These results supplied a novel technique for prenylated resveratrols production. • iacE was an effective resveratrol prenyltransferase. • The product was identified to be 2- C -prenyl resveratrol. • The neuroprotective mechanisms of 2- C -prenyl resveratrol was revealed. [ABSTRACT FROM AUTHOR]

Impaired long-term memory, a complication of traumatic stress including hemorrhage shock and resuscitation (HSR), has been reported to be associated with multiple neurodegenerations. The ventral tegmental area (VTA) participates in both learned appetitive and aversive behaviors. In addition to being prospective targets for the therapy of addiction, depression, and other stress-related diseases, VTA glutamatergic neurons are becoming more widely acknowledged as powerful regulators of reward and aversion. This study revealed that HSR exposure induces memory impairments and decreases the activation in glutamatergic neurons, and decreased β power in the VTA. We also found that optogenetic activation of glutamatergic neurons in the VTA mitigated HSR-induced memory impairments, and restored β power. Moreover, hydrogen sulfide (H 2 S), a gasotransmitter with pleiotropic roles, has neuroprotective functions at physiological concentrations. In vivo, H 2 S administration improved HSR-induced memory deficits, elevated c-fos-positive vesicular glutamate transporters (Vglut2) neurons, increased β power, and restored the balance of γ-aminobutyric acid (GABA) and glutamate in the VTA. This work suggests that glutamatergic neuron stimulation via optogenetic assay and exogenous H 2 S may be useful therapeutic approaches for improving memory deficits following HSR. • Hemorrhage shock and resuscitation induces memory impairments and decreases the activation in glutamatergic neurons. • Hemorrhage shock and resuscitation decreases β power in the VTA. • Hydrogen sulfide improve hemorrhage shock and resuscitation induced memory deficits. • Hydrogen sulfide elevates vesicular glutamate transporters neurons, increased β power. • Hydrogen sulfide has neuroprotective functions at physiological concentrations. [ABSTRACT FROM AUTHOR]

In the current paper we consider an inverse boundary value problem of electromagnetism with nonlinear Second Harmonic Generation (SHG) process. We show the unique determination of the electromagnetic material parameters and the SHG susceptibility parameter of the medium by making electromagnetic measurements on the boundary. We are interested in the case when a frequency is fixed. [ABSTRACT FROM AUTHOR]

Fibrotic scarring is tightly linked to the development of heart failure in patients with post-myocardial infarction (MI). Atypical chemokine receptor 4 (ACKR4) can eliminate chemokines, such as C–C chemokine ligand 21 (CCL21), which is independently associated with heart failure mortality. However, the role of ACKR4 in the heart during MI is unrevealed. This study aimed to determine whether ACKR4 modulates cardiac remodeling following MI and to illuminate the potential molecular mechanisms. The expression of ACKR4 was upregulated in the border/infarct area, and ACKR4 was predominantly expressed in cardiac fibroblasts (CFs). Knockout of ACKR4 protected against adverse ventricular remodeling in mice post-MI. These protective effects of ACKR4 deficiency were independent of dendritic cell immune response but could be attributed to downregulated CF-derived IL-6, affecting CF proliferation and endothelial cell (EC) functions, which consequently inhibited cardiac fibrosis. ACKR4 promoted IL-6 generation and proliferation of CFs. Besides, ACKR4 induced endothelial-to-mesenchymal transition (EndMT) in ECs through IL-6 paracrine effect. The p38 MAPK/NF-κB signaling pathway was involved in ACKR4 facilitated IL-6 generation. Moreover, ACKR4 overexpression in vivo via AAV9 carrying a periostin promoter aggravated heart functional impairment post-MI, which was abolished by IL-6 neutralizing antibody. Therefore, our study established a novel link between ACKR4 and IL-6 post-MI, indicating that ACKR4 may be a novel therapeutic target to ameliorate cardiac remodeling. • ACKR4 expression is upregulated in infarcted heart and exclusively detected in CFs. • ACKR4 deletion alleviates cardiac remodeling after MI. • The cardioprotective effect induced by ACKR4 deletion is DCs-trafficking independent. • Knockout of ACKR4 reduces proliferation, IL-6 generation of CFs in vitro. • Overexpression of ACKR4 aggravates cardiac dysfunction after MI via IL-6 in vivo. [ABSTRACT FROM AUTHOR]

There is a growing surge of investigative research involving the beneficial use of cannabinoids as novel interventional alternatives for multiple sclerosis (MS) and associated neuropathic pain (NPP). Using an experimental autoimmune encephalomyelitis (EAE) animal model of MS, we demonstrate the therapeutic effectiveness of two cannabinoid oil extract formulations (10:10 & 1:20 – tetrahydrocannabinol/cannabidiol) treatment. Our research findings confirm that cannabinoid treatment produces significant improvements in neurological disability scoring and behavioral assessments of NPP that directly result from their ability to reduce tumor necrosis factor alpha (TNF-α) production and enhance brain derived neurotrophic factor (BDNF) production. Henceforth, this research represents a critical step in advancing the literature by scientifically validating the merit for medical cannabinoid use and sets the foundation for future clinical trials. Cannabinoid treatment produces improvements in neurological disability scoring. Cannabinoid treatment also improves behavioral assessments of neuropathic pain. Cannabinoid treatment reduces TNF-α production and enhance BDNF production. EAE induction was responsible for the significant reduction of 5hmC. Pharmacokinetic pattern of cannabinoid oil extracts is investigated. [ABSTRACT FROM AUTHOR]

Abstract A plano-concave lens based on a one-dimensional (1D) ternary photonic crystal (PhC) was proposed, which was formed by periodic repetition of dielectric material layers MgF 2 , Ge, and SiO 2. The dispersion relation and transmission spectrum of the 1D ternary PhC were obtained by the transfer matrix method (TMM). The plano-concave lens can achieve sub-wavelength focusing due to negative refraction. The negative refraction band can be moved to the visible light band with specific parameter adjustment. A broadband focusing in the visible wavelength range from 580 nm to 755 nm was demonstrated. Changes of light intensity and full width at half maximum (FWHM) with focusing wavelength (FW) were investigated and a focal point with almost a theoretical minimum FWHM of 0.275 λ was obtained at a wavelength of 675 nm. The functional relationship between the FW and the focal distance was derived theoretically. The theoretical calculation results are basically consistent with the numerical results. The results provide a promising methodology and theoretical guidance for the application of sub-wavelength focusing of 1D ternary PhC plano-concave lenses. Highlights • A plano-concave lens based on a 1D ternary PhC was proposed. • The negative refraction band can be moved to the visible light band with specific parameter adjustment. • A broadband focusing in the visible wavelength range from 580 nm to 755 nm was demonstrated. • A focal point with almost a theoretical minimum FWHM of 0.275 λ was obtained. • The functional relationship between the focusing wavelength and the focal distance was derived theoretically. [ABSTRACT FROM AUTHOR]

During the process of wave-in-deck when waves impacting a horizontal platform deck from below, large air cavity entrainment would be generated between the free wave surface and the deck. The air entrainments are compressed and expanded during the process of wave impacts. As the momentum and energy exchange medium in the interactions between waves and the structure, air entrainments conversely influence the forces on the deck, risking structural safety. The key to dealing with the air entrainment is the combination of the mass source wave method and pressure-based compressible technique in capturing the cavity volume variation. In this work, the advanced compressible two-phase model is first developed with our in-house solver to simulate a regular wave impacting a fixed flat plate. The air cavity kinematics/dynamics and their relationship with wave impact features in the process of wave-in-deck impacting are discussed, and the mechanism of the compression/expansion effect is carefully analysed. Two distinct impacting types, direct water impact and entrained-air impact, are identified in this work, and the larger wave impacting pressures in the latter situation with compressible air layer is demonstrated. The good comparison of the numerical results and laboratory data on pressure features reveals that the proposed model is capable of reproducing the nonlinear entrained-air wave impacts and accurate oscillating pressures on a flat deck for applications. [ABSTRACT FROM AUTHOR]

Three different aspect ratios ( AR = rods length/rods width, AR = 2.8, 3.3, 3.8) of Au nanorods were synthesized and characterized by various measurements. We have evaluated the AR -dependent catalytic properties of Au nanorods using a model reaction based on the reduction of 4-nitrophenol (4-NP) by NaBH 4 . From the average reaction rate constants ( k ) at different temperatures, the activation energy ( E a ) was determined. For different aspect ratios of Au nanorods, the larger AR owns the higher k , and the values of E a increase with decreasing AR , meaning Au nanorods with the higher AR performed the higher catalytic activity. The thermodynamic parameters of entropy (Δ S ), Gibbs free energy (Δ G ) and activation enthalpy (Δ H ) indicated that this catalytic reduction is a non-spontaneous process. The catalytic results of Au nanorods clearly showed that the larger aspect ratio the higher catalytic activity. This substantial difference in AR- dependent catalytic activity can be explained from three different points: The superior catalytic properties of Au nanorods with higher AR result from higher surface-to-volume ratios; Au nanorods with lower AR needs to cross the higher energy barriers; Au nanorods with a larger AR may have higher fractions of uncoordinated surface atoms because of their increased surface curvature. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON) can affect health and growth performance of pigs, resulting in significant economic losses in swine production. The aim of this study was to investigate the effect of glycyrrhizic acid combined with compound probiotics, i.e. Enterococcus faecalis plus Saccharomyces cerevisiae (GAP) on improving growth performance, intestinal health and its fecal microbiota composition change of piglets challenged with DON. A total of 160 42-day-old weaned piglets (Landrace × Large White) were used and the experimental period was 28 d. The results showed that supplementing GAP in the diet significantly improved the growth performance of piglets challenged with DON and alleviate DON-induced intestinal damage by reducing ALT, AST and LDH concentrations in serum, increasing the morphological parameters of jejunum, and decreasing DON residues in serum, liver and feces. Moreover, GAP could significantly decrease the expressions of inflammation and apoptosis genes and proteins (IL-8, IL-10, TNF-α, COX-2, Bax, Bcl-2 and Caspase 3), and increase the expressions of tight-junction proteins and nutrient transport factor genes and proteins (ZO-1, Occludin, Claudin-1, ASCT2 and PePT1). In addition, it was also found that GAP supplementation could significantly increase the diversity of gut microbiota, maintain microbial flora balance and promote piglet growth by significantly increasing the abundance of beneficial bacterium such as Lactobacillus and reducing the abundance of harmful bacterium such as Clostridium_sensu_stricto_1. In conclusion, GAP addition to piglet diets contaminated with DON could significantly promote the health and growth performance of piglets though alleviating DON-induced hazards. This study provided a theoretical basis for the application of GAP to alleviate DON toxicity for animals. • Glycyrrhizic acid and compound probiotics decrease DON-induced growth inhibition and DON residues in weaned piglets. • Glycyrrhizic acid and compound probiotics alleviated DON-induced intestinal inflammation and apoptosis. • Glycyrrhizic acid and compound probiotics enhanced intestinal barrier and nutrient transport functions during DON exposure. • Glycyrrhizic acid and compound probiotics alleviated DON-induced intestinal damage and intestinal microbial imbalance. [ABSTRACT FROM AUTHOR]

Myostatin is an important member of the transforming growth factor (TGF) family that functions to regulate muscle growth in animals. In this study, the myostatin gene ( FmMstn ) and two slightly different (short and long forms) cDNAs of the banana shrimp Fenneropenaeus merguiensis were cloned and characterized. Similar to Mstn gene of the scallop, fish and mammal, FmMstn gene consists of 3 exons and 2 introns. The 2 kb upstream promoter region of the FmMstn gene consists of putative response elements for myocyte enhancing factor (MEF2) and E-box factors. The longest open reading frame of the short Mstn consists of 1260 bp encoding for a protein with 420 amino acid residues. The long FmMstn is almost identical to the short FmMstn with the exception of 8 amino acid insertions. FmMstn is most similar to the Mstn of Litopenaeus vannamei and Penaeus monodon sharing >92–98% amino acid sequence identity. Multiple sequence alignment results revealed high degree of amino acid conservation of the cysteine residues and mature peptide of the FmMstn with Mstn from other animals. FmMstn transcript was detected in the heart, muscle, optic nerve and thoracic ganglion. FmMstn transcript level in muscle is higher in early postmolt, decreases in intermolt and increases again towards ecdysis. Higher expression level of FmMstn is also observed in smaller shrimp of the same age. Knock-down of FmMstn gene by RNAi can cause a significant increase in molt cycle duration and failure of some shrimp to undergo ecdysis. Direct DNA sequencing results revealed that FmMstn gene is highly polymorphic and several potential SNPs have been identified. Some SNPs are associated with the size difference of the shrimp. In summary, the result of this study indicates that shrimp FmMstn gene is molt/growth-related and the presence of SNP suggests that it could be a candidate gene for shrimp genetic improvement research. [ABSTRACT FROM AUTHOR]

• Bending angle sensing based on tapered POF with double U-shaped configuration. • POF taper encapsulated with PDMS film for highly sensitive bending angle sensing. • The sensor shows highly sensitive response for joint bending detection. Finger joint angle measurements are important for the fields such as treatment of joint diseases, health monitoring, wearable devices, etc. As an effective detecting device, the joint angle monitoring sensor should have wide measurement angle range, and high sensitivity. In addition, the sensor should have good skin affinity, so as to enhance the degree of comfort for the user. In this paper, high-sensitivity bending angle sensing based on tapered plastic optical fiber (POF) configuration is proposed. The sensing performance is enhanced by tapering the POF and bending the POF taper to form a double U-shaped configuration then encapsulated with Polydimethylsiloxane (PDMS) film, therefore, the POF taper will be bent at three positions simultaneously, so that the bend induced loss will increase. The experimental preparation process of tapered POF and PDMS film package are presented in detail. The influence of taper waist diameter, and bending diameter on the bending loss has been investigated and optimized to enhance the angle sensitivity of the double U-shaped configuration. The results show that the sensitivity can reach 0.070 dB/° with a linearity of 0.995 in a wide bending angle range of 0-105°. The POF sensor is then applied for the joint bending detection. The experimental results show that the sensor can quickly respond to small pressures, and the variation of bending angles can be distinguished in the detection of joint bending. The proposed POF bending sensor shows the advantages of wide measurement angle range, high sensitivity, low cost and good portability, and shows important potential applications in the fields such as human joint movement detection. [ABSTRACT FROM AUTHOR]

Muscle deterioration caused by endogenous enzymes can greatly impact the quality of shrimp products during their processing and storage. In this study, the changes in trypsin, calpain, and cathepsin activity and their effects on muscle proteins in the intact and beheaded shrimp during 120 days of frozen storage were investigated. The results showed that the hardness, stretching force, chewiness, myofibrillar protein (MP) content, and Ca2+-ATPase activity significantly decreased in both the intact and beheaded shrimp samples with the prolonged storage period. Notably, the beheaded shrimp exhibited more stable characteristics than the intact shrimp samples throughout frozen storage. The endogenous enzyme analysis showed that the variations in the trypsin, calpain, and cathepsin activities were significantly pronounced in the intact shrimp compared to those in the beheaded samples. Furthermore, the myofibrillar fragmentation index, SDS-PAGE, and histological structure analysis revealed that the beheading treatment on the shrimp greatly inhibited the dissociation of muscle proteins during frozen storage. Our findings showed that the trypsin in the head of shrimp could be transferred to muscle tissues through the first abdominal segment during long-term storage, thus accelerating the degradation of MPs in the muscle tissues. Therefore, the beheading treatments effectively prolonged the shelf-life of stored shrimp products. • Alterations in endogenous enzymes in intact and beheaded shrimp were investigated. • Physicochemical properties of muscle proteins decreased with prolonged storage period. • Endogenous enzymes induced damage on MPs during storage. • Beheaded shrimp exhibited stable characteristics than intact samples. • Trypsin might be transferred from head to muscle accelerating degradation of MPs. [ABSTRACT FROM AUTHOR]

Blood–brain barrier (BBB) dysfunction is a key event in the development of many central nervous system (CNS) diseases, such as septic encephalopathy and stroke. 4,4′-Diaminodiphenylsulfone (DDS, Dapsone) has displayed neuroprotective effect, but whether DDS has protective role on BBB integrity is not clear. This study was designed to examine the effect of DDS on lipopolysaccharide (LPS)-induced BBB disruption and oxidative stress in brain vessels. Using in vivo multiphoton imaging, we found that DDS administration significantly restored BBB integrity compromised by LPS. DDS also increased the expression of tight junction proteins occludin, zona occludens-1 (ZO-1) and claudin-5 in brain vessels. Level of reactive oxygen species (ROS) was reduced by DDS treatment, which may due to decreased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and NOX2 expression. Our results showed that LPS-induced BBB dysfunction could be attenuated by DDS, indicated that DDS has a therapeutic potential for treating CNS infection and other BBB related diseases. [ABSTRACT FROM AUTHOR]

Highlights: [•] PLTP deficiency impaired blood–brain barrier (BBB) integrity. [•] PLTP deficiency decreased tight junctions (TJs) expression in brain vessels. [•] PLTP deficiency increased cerebrovascular oxidative stress. [•] Vitamin E supplementation restored TJs expression and BBB integrity. [ABSTRACT FROM AUTHOR]

Globally, the payments for ecosystem services (PES) program has become a helpful tool that serves the purpose of mitigating ecosystem degradation and protecting ecosystem services. However, the ecological effects of existing PES programs based on counterfactual baselines, quantification and sophisticated statistical analyses are still poorly understood. Taking Inner Mongolia as an example, this study evaluated the ecological effectiveness of the Natural Forest Conservation Program (NFCP) using the matching approach. The findings are as follows. First, 49.8% and 41.5% of the townships had significant gains in vegetation quantity and quality between 2000 and 2015, respectively; while 9.5% and 13.7% of the townships had significant losses in vegetation quantity and quality, respectively. Second, for forest quantity recovered townships, comparing to the NFCP unenrolled townships, the enrolled townships had increased forest quantity by additional 0.377 million ha (5.2%) from 2000 to 2015. Third, for forest quality recovered townships, the enrolled townships on average additionally increased forest quality by 465.513 Gg carbon (3.6%) from 2000 to 2015. Our study helps to promote sophisticated impact evaluation of conservation policies, which would improve the understanding and management of conservation practices in China and abroad. [Display omitted] • Quasi-experimental designs can successfully evaluate the impact of payments for ecosystem services programs. • Approximately 77.4% and 65.2% of the forest-covered townships have significantly recovered in forest quantity and quality. • The Natural Forest Conservation Program (NFCP) has additionally increased forest quantity recovery by 5.2%. • The NFCP enrolled forest has additionally increased forest quality recovery by 3.6%. [ABSTRACT FROM AUTHOR]

Abstract: Background: Septic encephalopathy is characterized by changes in mental status and an increase in neuronal apoptosis. Accumulating evidence has shown that recombinant human erythropoietin (rhEPO) protects brain against ischemia and hypoxia injury. However, whether rhEPO exerts neuroprotective effects on septic encephalopathy remains unclear. We designed the current study to evaluate possible neuroprotection of rhEPO in a model of sepsis. Methods: For this in vitro study, we determined hippocampal neuronal apoptosis by lactate dehydrogenase release, cell counting kit-8 assay, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining after treatment with lipopolysaccharide. We transfected the signal transducer and activator of transcription 3 (STAT3) short hairpin RNA at 14 d in vitro for 48 h. For the in vivo study, we performed cecal ligation and peroration surgery. We detected the expression of phospho-Janus-activated kinase 2 (JAK2), total JAK2, phospho-STAT3, total STAT3, Bax and Bcl-XL by Western blot, and examined behavior using the Morris water maze. Results: Treatment with rhEPO reduces apoptosis and increases cell viability in lipopolysaccharide-treated neuronal cultures. In cecal ligation and peroration rats, rhEPO attenuated the inhibition of phospho-JAK2 and phospho-STAT3. In addition, rhEPO enhanced the expression of Bcl-XL, but depressed Bax, which was abolished by additional administration of inhibitor of JAK2/STAT3 signaling 2-cyano-3-(3,4-dihydroxyphenyl)-N-(benzyl)-2-propenamide,2-cyano-3-(3,4-dihydroxyphenyl)-N-(phenylmethyl)-2-propenamide or (E)-3(6-bromopyridin-2-yl)-2-cyano-N-([S0-1-phenylethyl]acrylamide)in vivo, and was ameliorated by STAT3 short hairpin RNA transfection in vitro. Alternatively, we confirmed the neuronal protective effect of rhEPO by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelingstaining. For the Morris water maze study, rhEPO improved learning and memory disorders without an alternation in locomotor activity. Conclusions: These results indicated that rhEPO improves brain dysfunction by reducing neuronal apoptosis, and JAK2/STAT3 signaling is likely to be involved. Application of rhEPO may serve as a potential therapy for the treatment of septic encephalopathy. [Copyright &y& Elsevier]

Abstract: The interactions of BSA with a series of cationic imidazolium gemini surfactants ([C n -s-C n im]Br2, n =10, 12, 14, s =2, 4, 6), quaternary ammonium surfactants (C12C2C12), and their corresponding monomers ([C12mim]Br and DTAB) are investigated by fluorescence using pyrene as a molecular probe, synchronous fluorescence, circular dichroism (CD), and UV–visible absorption spectra. These surfactants are used to elucidate the effects of surfactant hydrophilic head group, spacer length, and hydrophobic chain length on the conformation of BSA. The results of fluorescence spectra and CD show that the imidazolium gemini surfactants with shorter spacers or with longer hydrophobic chains have a larger effect on BSA unfolding, and the imidazolium gemini surfactant interacts with BSA more strongly than its corresponding monomer and the quaternary ammonium gemini surfactant. These conclusions have been confirmed by the binding constants (Ka ) and binding sites (n) for the BSA/surfactant system. Stern–Volmer quenching constants KSV of cationic surfactants binding to BSA are obtained, indicating that the probable quenching mechanism is initiated by ground-state complex formation rather than by dynamic collision. Moreover, the synchronous fluorescence spectra show that the surfactants mainly interact with tryptophan residues of BSA. [Copyright &y& Elsevier]

Abstract: Honeybees may be exposed to insecticidal proteins from transgenic plants via pollen. An assessment of the impact of such exposures on the honeybee is an essential part of the risk assessment process for transgenic Bacillus thuringiensis corn. A field trial was conducted to evaluate the effect of transgenic Bt cry1Ah corn on the honeybee Apis mellifera ligustica. Colonies of honeybees were moved to Bt or non-Bt corn fields during anthesis and then sampled to record their survival, development and behavior. No differences in immature stages, worker survival, bee body weight, hypopharyngeal gland weight, colony performance, foraging activity or olfactory learning abilities were detected between colonies that were placed in non-Bt corn fields and those placed in Bt corn fields. We conclude that cry1Ah corn carries no risk for the survival, development, colony performance or behavior of the honeybee A. mellifera ligustica. [Copyright &y& Elsevier]

Abstract: Pyrethroids act on the nervous system as a primary target organ and exert their neurotoxic effects primarily by altering the conductance of sodium channel, leading to hyperexcitation. However, few studies investigated the effects of pyrethroids on neuronal excitability of honeybee brain neurons. In this study, a whole-cell patch-clamp technique was used to record current threshold, the minimum current to induce an action potential, and peak sodium current in the dissociated honeybee brain neurons treated with bifenthrin, deltamethrin and fluvalinate in vitro & in vivo. The study showed that these pyrethroids greatly suppressed the neuronal excitability as revealed by increasing current injected and inhibited the peak sodium current in honeybees. The three pyrethroids also inhibited steady-state inactivation in addition to reduction of sodium peak current. [Copyright &y& Elsevier]

Previous studies have found associations between single toxic metals, such as arsenic and cadmium, and kidney function in adults with diabetes. However, studies with regards to other metals and metal mixtures are still limited. Our study aimed to investigate the associations between urinary concentrations of 5 selected metals and metal mixtures and kidney function using a sample of older adults with diabetes mellitus in Chinese communities. In a sample of older adults (n = 5186), 592 eligible subjects were included in this study. Urinary concentrations of 5 metals, i.e., arsenic (As), cadmium (Cd), vanadium (V), cobalt (Co), and thallium (Tl), were measured by inductively coupled plasma mass spectrometer (ICP-MS). Estimated glomerular filtration rate (eGFR) was calculated and dichotomized into indicator of chronic kidney disease (CKD). Logistic analysis and Bayesian kernel machine regression (BKMR) were used to explore the associations between single metals and metal mixtures and CKD, respectively. Urinary levels of As and V were positively correlated with CKD (OR =2.37, 95% CI : 1.31–4.30 for As; OR =2.24, 95% CI : 1.25–4.03 for V), when compared the 4th quartile with the 1st quartile. After adjustment for potential confounders, the significant association between As and CKD still existed (OR =2.73, 95% CI : 1.23–6.07). BKMR analyses showed strong linear positive associations between As and V and CKD. Higher urinary levels of the mixture were significantly associated with higher odds of CKD in a dose-response pattern. As and V showed the highest posterior inclusion probabilities. Urine As and V were positively associated with CKD in older adults with diabetes mellitus, separately and in a mixture. The metals mixture showed a linear dose-response association with the odds of CKD. The analyses of mixtures, rather than of single metals, may provide a real-world perspective on the relationship between metals and kidney function. • Urine As and V were significantly associated with CKD in single metal models. • The overall harmful effects of 5 selected metals on kidney function were observed. • As and V made major contributions to kidney function among mixtures. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the cost-effectiveness of niraparib versus routine surveillance as maintenance therapy for patients with platinum-sensitive recurrent ovarian cancer in China. A three-state partitioned survival model that adopted a lifetime horizon with a 4-week cycle length was developed. Efficacy data were derived from the NORA study. Cost and utility data were obtained from published studies and online databases. The cost and health outcomes were discounted at an annual rate of 5%. In this analysis, the primary outcomes included quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio (ICER). The willingness-to-pay (WTP) thresholds were set at 1 to 3 times the gross domestic product per capita of China in 2022 ($12,741 to $38,233/QALY). Sensitivity analyses were conducted to verify the robustness of the model results. In the base-case analysis, niraparib was not found to be cost-effective, with an ICER of $42,888/QALY compared with routine surveillance at the WTP thresholds. One-way deterministic sensitivity analyses indicated that the ICER value was most sensitive to the cost of subsequent treatment in placebo group. The probabilistic sensitivity analysis suggested that at the WTP thresholds, the probability of niraparib being cost-effective was 2.9% to 50.1%. Niraparib improves the survival benefit of platinum-sensitive recurrent ovarian cancer patients. However, it seems to be less cost-effective, as it has higher costs than routine surveillance at the WTP thresholds. Reasonable dose reduction according to the patient's actual situation or lowering the price of niraparib can improve its cost-effectiveness. • Limited economic evidence of niraparib for platinum-sensitive recurrent ovarian cancer is provided in China. • Niraparib is less cost-effective than routine surveillance in China. • The cost-effectiveness of niraparib will be improved by lowing its price. [ABSTRACT FROM AUTHOR]

Let μ = μ { R n , B n } = δ R 1 − 1 B 1 ⁎ δ (R 2 R 1) − 1 B 2 ⁎ ⋯ be a Borel probability measure with a compact support, where R n ∈ M 2 (Z) , B n ⊂ Z 2 and (R n , B n , L n) forms a Hadamard triple for all n ≥ 1. In this paper, we consider the existence of exponential orthogonal basis in L 2 (μ). We extend the concept of equi-positive family in [1] to higher dimensions, and provide a new idea to characterize the spectrality of such measures. In details, we study the spectrality and non-spectrality of Moran-Sierpinski type measures specifically under some necessary assumptions. The partial findings of several previous studies are extended by this study, such as Cantor-Moran measures (An-Fu-Lai [1] , An-He-He [3]), Moran-Sierpinski type measures (Wang-Dong [47]) and Moran-Cantor-Dust type measures (Chen-Liu-Su-Wang [9]). [ABSTRACT FROM AUTHOR]

Myocardial Ischemic Injury is a serious threat to human health, and DJ-1 is involved in cardioprotection. The research intended to explore the effects and mechanism of DJ-1 to protect myocardium against ischemia injury. DJ-1 overexpression lentivirus vectors were transduced into the myocardium of SD rats and H9c2 cells, and an AMI model in vivo and a hypoxia model in vitro were established, respectively. Results showed that DJ-1 overexpression alleviated myocardial ischemia injury, as demonstrated by reduced the extent of myocardial infarction, improved cell survival, decreased LDH activity and CK-MB release. Furthermore, DJ-1 interacted with RACK1, activated AMPK/mTOR pathway, induced adaptive autophagy and protected the myocardium. However, RACK1 siRNA or compound C (an AMPK inhibitor) could weaken the above effect of DJ-1 on myocardium. In conclusion, DJ-1 could activate adaptive autophagy by the RACK1/AMPK/mTOR pathway and protect the myocardium against ischemia injury. • DJ-1 induces adaptive autophagy to protect myocardium against ischemia injury. • DJ-1-RACK1 complex acts as a novel autophagy regulator. • The function of DJ-1 protein depends on the cysteine residue at C106. • Targeting DJ-1 to activate AMPK/mTOR signaling-novel strategy for the treatment of Ischemic heart disease. [ABSTRACT FROM AUTHOR]

Dual-source drinking water distribution systems (DWDS) over single-source water supply systems are becoming more practical in providing water for megacities. However, the more complex water supply problems are also generated, especially at the hydraulic junction. Herein, we have sampled for a one-year and analyzed the water quality at the hydraulic junction of a dual-source DWDS. The results show that visible changes in drinking water quality, including turbidity, pH, UV 254 , DOC, residual chlorine, and trihalomethanes (TMHs), are observed at the sample point between 10 and 12 km to one drinking water plant. The average concentration of residual chlorine decreases from 0.74 ± 0.05 mg/L to 0.31 ± 0.11 mg/L during the water supplied from 0 to 10 km and then increases to 0.75 ± 0.05 mg/L at the end of 22 km. Whereas the THMs shows an opposite trend, the concentration reaches to a peak level at hydraulic junction area (10–12 km). According to parallel factor (PARAFAC) and high-performance size-exclusion chromatography (HPSEC) analysis, organic matters vary significantly during water distribution, and tryptophan-like substances and amino acids are closely related to the level of THMs. The hydraulic junction area is confirmed to be located at 10–12 km based on the water quality variation. Furthermore, data-driven models are established by machine learning (ML) with test R 2 higher than 0.8 for THMs prediction. And the SHAP analysis explains the model results and identifies the positive (water temperature and water supply distance) and negative (residual chlorine and pH) key factors influencing the THMs formation. This study conducts a deep understanding of water quality at the hydraulic junction areas and establishes predictive models for THMs formation in dual-sources DWDS. • The hydraulic junction area of dual-source DWDS was located. • Quantitative analysis of organic characterization is conducted by PARAFAC and HPSEC analysis. • Date-driven models for THMs prediction is established by ML. • The key factors that influencing THMs formation is identified by SHAP analysis. • The risks and advantages of dual-source DWDS are summarized. [ABSTRACT FROM AUTHOR]

• NAc neuroinflammation induced by intra-NAc injection of LPS leads to depressive-like disorders. • NAc neuroinflammation results in D3R expression decline and microglial activation in the NAc. • D3R in the NAc shows a crucial role in the initiation and development of depressive-like behaviors. • D3R inhibition could convert microglia toward a proinflammatory response. • D3R inhibition-induced proinflammatory microglia was primarily through the Akt signaling pathway. We recently reported that dopamine D3 receptor (D3R) was involved in inflammation-related depression. Nucleus accumbens (NAc) inflammation is implicated in the development and progression of depression, but its regulatory mechanism remains largely unknown. In a mouse model of NAc neuroinflammation induced by bilateral NAc injection of lipopolysaccharide (LPS), we observed that NAc neuroinflammation triggered depressive-like behaviors, and D3R expression decline and microglial activation in the NAc. A selective knockdown of D3R in the NAc elicited depressive-like behaviors, while re-expression of D3R in the NAc of global D3RKO mice alleviated depressive-like behaviors induced by D3R deficiency. D3R downregulation in the NAc shifted microglia toward a proinflammatory state, which was validated with cultured mouse microglial cultures. Further in vitro results demonstrated that D3R inhibition induced microglia to enter a proinflammatory state primarily through the Akt signaling pathway. In conclusion, our results suggest that D3R expression in the NAc may inhibit microglial proinflammatory responses in the NAc, thus alleviating NAc neuroinflammation and subsequent depressive-like behaviors through the Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Some of the statins have been shown to have antidepressant effects, but whether atorvastatin (AV) has antidepressant effects is unknown. This study was to investigate the effect of AV treatment on depressive behaviors. Herein, we show that AV treatment had antidepressant-like effect in physiological conditions and antidepressant effect in depressive state which depended on α7 nicotinic acetylcholine receptor (α7nAChR) expression in the ventral hippocampus (vHPC), but not α4β2 nicotinic acetylcholine receptor (α4β2nAchR) expression in vHPC, nor the α7nAChR and α4β2nAchR expression in dorsal hippocampus (dHPC). By using MLA, a selective α7nAChR antagonist, we investigated the role of α7nAChR in AV treatment. Behavior tests demonstrated that MLA abolished the antidepressant effect of AV. Besides, our data showed that AV treatment increased Akt phosphorylation, brain-derived neurotrophic factor (BDNF), synaptic related protein synapsin and spinophilin expression. The phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002 reversed AV-induced increase of BDNF expression, newborn neurons and antidepressant behavior effects. Our study suggests that AV plays an antidepressant role by regulating synaptic plasticity of vHPC through PI3K/Akt-BDNF signaling pathway, which may be a good choice for depression treatment. • Atorvastatin alleviates CUMS-induced depression behaviors in mice. • Atorvastatin exerts antidepressant effect by up-regulating the α7nAchR expression in vHPC. • Atorvastatin exerts antidepressant effect by up-regulating the p-Akt, BDNF expression in vHPC. • Atorvastatin exerts antidepressant effect by up-regulating hippocampal neuronal proliferation. • Atorvastatin alleviates depressive behaviors via regulation of α7nAChR-PI3K/Akt-BDNF pathway. [ABSTRACT FROM AUTHOR]

Rivers have been widely reported as important CO 2 emitters to the atmosphere. Rapid urbanization has a profound impact on the carbon biogeochemical cycle of rivers, leading to enhanced riverine CO 2 evasions. However, it is still unclear whether the spatial–temporal patterns of CO 2 emissions in the rivers draining diverse landscapes dominated by urbanization were stable, especially in mountainous areas. This study carried out a two-year investigation of water environmental hydrochemistry in three small mountainous rivers draining urban, suburban and rural landscapes in southwestern China, and CO 2 partial pressure (p CO 2) and fluxes (f CO 2) in surface water were measured using headspace equilibrium method and classical thin boundary layer model. The average p CO 2 and f CO 2 in the highly urbanized river were of 4783.6 μatm and 700.0 mmol m−2 d−1, conspicuously higher than those in the rural river (1525.9 μatm and 123.2 mmol m−2 d−1), and the suburban river presented a moderate level (3114.2 μatm and 261.2 mmol m−2 d−1). It provided even clearer evidence that watershed urbanization could remarkably enhance riverine CO 2 emissions. More importantly, the three rivers presented different longitudinal variations in p CO 2 , implying diversified spatial patterns of riverine CO 2 emissions as a result of urbanization. The urban land can explain 49.6–69.1% of the total spatial variation in p CO 2 at the reach scale, indicating that urban land distribution indirectly dominated the longitudinal pattern of riverine p CO 2 and f CO 2. p CO 2 and f CO 2 in the three rivers showed similar temporal variability with higher warm-rainy seasons and lower dry seasons, which are significantly controlled by weather dynamics, including monthly temperature and precipitation, but seem to be impervious to watershed urbanization. High temperature-stimulated microorganisms metabolism and riched-CO 2 runoff input lead much higher p CO 2 in warm-rainy seasons. However, it showed more sensitivity of p CO 2 to monthly weather dynamics in urbanized rivers than that in rural rivers, and warm-rainy seasons showed hot moments of CO 2 evasion for urban rivers. TOC, DOC, TN, pH and DO were the main controls on p CO 2 in the urban and suburban rivers, while only pH and DO were connected with p CO 2 in the rural rivers. This indicated differential controls and regulatory processes of p CO 2 in the rivers draining diverse landscapes. Furthermore, it suggested that p CO 2 calculated by the pH-total alkalinity method would obviously overestimate p CO 2 in urban polluted rivers due to the inevitable influence of non-carbonate alkalinity, and thus, a relatively conservative headspace method should be recommended. We highlighted that urbanization and weather dynamics co-dominated the multiformity and uncertainty in spatial–temporal patterns of riverine CO 2 evasions, which should be considered when modeling CO 2 dynamics in urbanized rivers. [Display omitted] • The effects of urbanization and meteorological factors on riverine p CO 2 were quantified. • Urban watershed activities could remarkably enhance riverine CO 2 emissions. • Urban land distribution indirectly dominated the longitudinal pattern of riverine p CO 2. • Seasonal variations in p CO 2 in urbanized rivers was more sensitive to meteorological factors. • Controls and regulatory processes of p CO 2 between urbanized with rural rivers were different. [ABSTRACT FROM AUTHOR]

When cropland expansion encroaches on ecological land (e.g., forest, grassland, wetland), it seriously affects carbon storage which plays an important role in global climate change. Taking Hubei as the study area, this study explored the effects of cropland expansion on carbon storage in both 2000–2010 and 2010–2030 in different scenarios by using the Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) model and the LAND System Cellular Automata model for Potential Effects (LANDSCAPE). The results showed that cropland expansion led to a massive loss of carbon storage (1.76 Tg C) during 2000–2010, which is expected to continue during 2010–2030 in different scenarios. The loss is predicted to be 3.70 Tg C in the Business-As-Usual scenario and be 0.88 Tg C in the Requisition–Compensation Balance of Cropland Policy scenario. Noticeably, the loss of carbon storage due to cropland expansion was 1.12 times more than that due to urban expansion during 2000–2010. For the period of 2010–2030, the loss of carbon storage caused by cropland expansion is predicted to be 3.89 times more than that caused by urban expansion in the Business-As-Usual scenario, while the losses caused by cropland expansion and urban expansion are predicted to be almost equal in the Requisition–Compensation Balance of Cropland Policy scenario. The main cause of carbon storage loss due to cropland expansion is that it leads to the considerable loss of forest and wetland. This study highlights the importance of considering the loss of carbon storage caused by cropland expansion when conducting cropland protection policies and land use planning. • Loss of carbon storage caused by cropland expansion is comparable to or greater than that from urban expansion. • Carbon storage loss caused by cropland expansion is projected to be significantly different in different scenarios. • The loss of forest and wetland is the main reason for carbon storage loss. [ABSTRACT FROM AUTHOR]

• D3R was expressed in astrocyte and microglia in the mesolimbic reward regions of normal mice. • D3R deficiency resulted in microglial activation in the mesolimbic dopaminergic brain regions. • Microglial inhibition partially ameliorated depressive-like behavior and neuroinflammation in the selected mesolimbic reward areas induced by D3R deficiency. • Microglial inhibition attenuated the elevation in BDNF expression and synaptic density in the NAc in D3RKO mice. We previously demonstrated that the dopamine D3 receptor (D3R) inhibitor, NGB2904, increases susceptibility to depressive-like symptoms, elevates pro-inflammatory cytokine expression, and alters brain-derived neurotrophic factor (BDNF) levels in mesolimbic dopaminergic regions, including the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and ventral tegmental area (VTA) in mice. The mechanisms by which D3R inhibition affects neuroinflammation and onset of depression remain unclear. Here, using D3R-knockout (D3RKO) and congenic wild-type C56BL/6 (WT) mice, we demonstrated that D3RKO mice displayed depressive-like behaviors, increased tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 levels, and altered BDNF expression in selected mesolimbic dopaminergic regions. D3R expression was localized to astrocytes or microglia in the mPFC, NAc, and VTA in WT mice. D3RKO mice exhibited a large number of Iba1-labelled microglia in the absence of glial fibrillary acidic protein (GFAP)-labelled astrocytes in mesolimbic dopaminergic brain areas. Inhibition or ablation of microglia by minocycline (25 mg/kg and 50 mg/kg) or PLX3397 (40 mg/kg) treatment ameliorated depressive-like symptoms, alterations in pro-inflammatory cytokine levels, and BDNF expression in the indicated brain regions in D3RKO mice. Minocycline therapy alleviated the increase in synaptic density in the NAc in D3RKO mice. These findings suggest that microglial activation in selected mesolimbic reward regions affects depressive-like behaviors induced by D3R deficiency. [ABSTRACT FROM AUTHOR]

Effective antimicrobial measures are needed to control cross-contamination and rapid spoilage of food caused by Vibrio parahaemolyticus (V. parahaemolyticus) and Pseudomonas fluorescens (P. fluorescens). This study evaluated the combined effect of electron beam irradiation (EBI) combined with slightly acidic electrolytic water (SAEW) treatment on suspended bacteria and single and dual-species biofilms of V. parahaemolyticus and P. fluorescens. Colony counting results showed that EBI combined with SAEW treatment effectively removed biofilm cells. Confocal laser scanning microscopy and ATP leakage analysis showed that EBI combined with SAEW treatment damaged the membrane integrity of biofilm cells and caused ATP leakage. Field emission scanning electron microscopy (SEM) observations showed that EBI with or without SAEW significantly disrupted the three-dimensional reticular structure of mono/co-cultured biofilm (extracellular polymeric substances) EPS, producing reticular perforation damage. Combined treatment with 60 mg/L SAEW and 0.5 kGy (kGy) EBI caused serious damage to the three-dimensional structure of the biofilms. The detection results of biofilm protein and DNA showed that EBI combined with SAEW could effectively destroy the extracellular polymeric matrix of biofilm, but the primary structure of the protein had no significant effect. These results suggest that SAEW(60 mg/L) combined with EBI(0.5 kGy) is effective in reducing microbial and biofilm attachment during the large yellow croaker storage processing. • 0.5 kGy EBI combined with 60 mg/L SAEW effectively inactivated the Vibrio parahaemolyticus and Pseudomonas fluorescens. • The three-dimensional structure of biofilms was damaged significantly by EBI combined with SAEW. • The damage of extracellular polymers in biofilms may be attributed to the degradation of polysaccharides and eDNA. [ABSTRACT FROM AUTHOR]

Isoxazoline drugs, including afoxolaner, fluralaner, lotilaner, and sarolaner, are widely used in veterinary medicine. However, the lack of available analytical methods has made regulatory monitoring of these drugs difficult. Therefore, in this study, we developed an optimized solid phase extraction process using hydrophilic–lipophilic cartridges, and subsequently analyzed the extracts using liquid chromatography–tandem mass spectrometry under optimized conditions. The detection limits for the four isoxazolines were 5.0 μg/kg, while the recoveries in six animal-derived matrices were 71.1–109.2 %, with intra-day and inter-day relative standard deviations below 11.9 % and 11.7 % respectively. Furthermore, an inter-laboratory comparison demonstrated that this method had good recovery (60.3–112.9 %) and acceptable precision (< 11.3 %). Additionally, the developed method exhibited excellent linearity, accuracy, precision, sensitivity, measurement uncertainty and robustness for isoxazoline residue determination in animal-derived samples. It was also successfully applied to determine incurred isoxazoline residues in medicated hens. [Display omitted] • A LC–MS/MS method for detection of isoxazolines in animal-derived matrix samples was developed. • A PRiME SPE purification technology was applied in the analysis of isoxazolines. • Applicability of the method to medicated chicken samples. • Interlaboratory comparisons were used to evaluate the precision of the analytical method. [ABSTRACT FROM AUTHOR]

Metallic iron (Fe0) particles with sizes ranging from a few nanometers to the submicroscopic scale and formed by space weathering are specific components of lunar soil. Previous studies have suggested that the iron significantly alters the optical properties of lunar soil. For example, nanophase metallic iron (npFe0) causes both reddening and darkening of the lunar soil spectrum, and submicroscopic metallic iron (SMFe) only causes darkening. Here, we prepared SMFe particles with an average size of ∼180 nm embedded within melt glasses through carbothermal reduction experiments to analogize agglutinated glasses in the lunar soil. We evaluated the effect of SMFe content on visible and near-infrared (VIS–NIR) reflectance spectra of these lunar soil samples simulants. The spectral data show that SMFe content plays a key role in the optical properties of samples, including the average reflectance in the VIS-NIR range (400–2150 nm), and the absorption depth at ∼2 μm. A small amount (0.05 wt%) of SMFe mainly causes significant spectral darkening, and the average reflectance is reduced by 50% when the SMFe content rises to 0.36 wt%. Both the average reflectance and the absorption depth at ∼2 μm show a negative correlation with the SMFe content. We developed a quantitative model relating the spectral characteristics and the SMFe abundance based on experimental results. Thus, the SMFe contents play a key role in altering spectral characteristics of airless bodies during remote sensing spectroscopic detection. • Metallic iron formed by space weathering are specific components of airless bodies. • Submicroscopic metallic iron plays a key role in changing the optical properties. • Submicroscopic metallic iron and average reflectance have a negative correlation. • Submicroscopic metallic iron and absorption depth have a negative correlation. [ABSTRACT FROM AUTHOR]

As the important intracellular secondary messengers, calcium channel is the target of many neurotoxic pesticides as calcium homeostasis in the neuroplasm play important role in neuronal functions and behavior in insects. This study investigated the effect of deltamethrin (DM) on calcium channel in the brain nerve cells of adult workers of Apis mellifera ligustica Spinola that were cultured in vitro . The results showed that the intracellular calcium concentration was significantly elevated even with a very low concentration of the DM (3.125 × 10 − 2 mg/L). Further testing revealed that T-type voltage-gated calcium channels (VGCCs), except for sodium channels, was one of the target of DM on toxicity of Apis mellifera , while DM has no significant effect on the L-type VGCCs, N -methyl- d -aspartate receptor-gated calcium channels and calcium store. These results suggesting that the DM may act on T-type VGCCs in brain cells of honeybees and result in behavioral abnormalities including swarming, feeding, learning, and acquisition. [ABSTRACT FROM AUTHOR]

Armadillo repeat proteins (ArmRPs) recognize their target peptide in extended conformation and bind, in a first approximation, two residues per repeat. Thus, they may form the basis for building a modular system, in which each repeat is complementary to a piece of the target peptide. Accordingly, preselected repeats could be assembled into specific binding proteins on demand and thereby avoid the traditional generation of every new binding molecule by an independent selection from a library. Stacked armadillo repeats, each consisting of 42 aa arranged in three α-helices, build an elongated superhelical structure. Here, we analyzed the curvature variations in natural ArmRPs and identified a repeat pair from yeast importin-α as having the optimal curvature geometry that is complementary to a peptide over its whole length. We employed a symmetric in silico design to obtain a uniform sequence for a stackable repeat while maintaining the desired curvature geometry. Computationally designed ArmRPs (dArmRPs) had to be stabilized by mutations to remove regions of higher flexibility, which were identified by molecular dynamics simulations in explicit solvent. Using an N-capping repeat from the consensus-design approach, two different crystal structures of dArmRP were determined. Although the experimental structures of dArmRP deviated from the designed curvature, the insertion of the most conserved binding pockets of natural ArmRPs onto the surface of dArmRPs resulted in binders against the expected peptide with low nanomolar affinities, similar to the binders from the consensus-design series. [ABSTRACT FROM AUTHOR]

Food-borne pathogens and biofilm formation pose a serious threat to seafood safety. The objective of this study was to evaluate the inactivation effect of electron beam irradiation on the suspension and biofilms of Vibrio parahaemolyticus (V. parahaemolyticus), Pseudomonas fluorescens (P. fluorescens) , and Shewanella putrefaciens (S. putrefaciens) in vitro and on the surface of large croaker and the possible mechanisms of action. The results showed that electron beam irradiation could significantly reduce the number of viable bacteria both in vitro and on the surface of the large yellow croaker samples and could destroy the extracellular polymers (EPS) of biofilms. Mechanism studies showed that the increased Reactive Oxygen Species (ROS) levels after irradiation treatment resulted in damage to the plasma membrane of bacterial cells, while the cell wall was intact. In addition, the nucleic acids of the bacteria were significantly damaged after irradiation, but the primary protein structure was not changed. These findings provide the internal mechanism of the effect of electron beam irradiation on Gram-negative bacteria and indicate that electron beam irradiation could be used as an effective method to control spoilage bacteria and pathogenic bacteria biofilms on the surface of seafood. • Electron beam irradiation above 0.5 kGy can disrupt the EPS system of biofilms and disperse the biofilms. • Electron beam irradiation above 0.5 kGy damaged the cytoplasmic membrane and the ROS penetrate into cells. • Electron beam irradiation above 1 kGy can be used to inactivate Gram-negative bacteria and biofilms on large yellow croaker. [ABSTRACT FROM AUTHOR]

To explore how Girdin/GIV is regulated by cyclic tension and propagates downstream signals to affect cell proliferation and migration. Human osteoblast-like MG-63 cells were exposed to cyclic tension force at 4000 μstrain and 0.5 Hz for 6 h, produced by a four-point bending system. Cyclic tension force upregulated Girdin and Akt expression and phosphorylation in cultured MG-63 cells. Girdin and Akt each promoted the phosphorylation of the other under stimulated tension. In vitro MTT and transwell assays showed that Girdin and Akt are required for cell proliferation and migration during cellular quiescence. Moreover, STAT3 was determined to be essential for Girdin expression under stimulated tension force in the physiological condition, as well as for osteoblast proliferation and migration during quiescence. These findings suggest that the STAT3/Girdin/Akt pathway activates in osteoblasts in response to mechanical stimulation and may play a significant role in triggering osteoblast proliferation and migration during orthodontic treatment. [ABSTRACT FROM AUTHOR]

The specific recognition of peptide sequences by proteins plays an important role both in biology and in diagnostic applications. Here we characterize the relatively weak binding of the peptide neurotensin (NT) to the previously developed Armadillo repeat protein VG_328 by a multidisciplinary approach based on solution NMR spectroscopy, mutational studies, and molecular dynamics (MD) simulations, totaling 20 μs for all MD runs. We describe assignment challenges arising from the repetitive nature of the protein sequence, and we present novel approaches to address them. Partial assignments obtained for VG_328 in combination with chemical shift perturbations allowed us to identify the repeats not involved in binding. Their subsequent elimination resulted in a reduced-size binder with very similar affinity for NT, for which near-complete backbone assignments were achieved. A binding mode suggested by automatic docking and further validated by explicit solvent MD simulations is consistent with paramagnetic relaxation enhancement data collected using spin-labeled NT. Favorable intermolecular interactions are observed in the MD simulations for the residues that were previously shown to contribute to binding in an Ala scan of NT. We further characterized the role of residues within the N-cap for protein stability and peptide binding. Our multidisciplinary approach demonstrates that an initial low-resolution picture for a low-micromolar-peptide binder can be refined through the combination of NMR, protein design, docking, and MD simulations to establish its binding mode, even in the absence of crystallographic data, thereby providing valuable information for further design. [ABSTRACT FROM AUTHOR]

Ascosphaera apis (Onygenales: Ascosphaeraceae) is a chalkbrood causing pathogen in honeybees. Recently, chemicals have been used against this disease. Consequently, the abuse of chemicals has caused serious impacts on the environment and honey quality and on honeybee colonies themselves. Therefore, the search for biological control options should be the priority for controlling chalkbrood disease. In this experiment, we employed restriction enzyme mediated integration (REMI) to construct mutants (transformants) with growth inhibition on A. apis in honeybees using the Trichoderma atroviride T23 wild strain. The integration of the plasmid pBluescript KS-EH1 into the REMI mutants was confirmed by PCR and Southern hybridization. As a result, ten single-copied T. atroviride T23 transformants were successfully identified. Furthermore, culture filtrates of the transformants, their wild strain and Shabaijing (a commercial fungicide, ethyl ethylsulfonothiolate) were tested to compare their in vitro growth inhibition capability on A. apis . The results demonstrated that transformants Tat5 and Tat6 had the highest growth inhibition activity with the minimal fungicidal concentration (v/v) of 3.5–4.5%. Thus, the Trichoderma transformants constructed by REMI could be used as potential biological agents against the growth of fungal diseases in bee hives. Further refinement and strategy development for the integrative use of this result are vital future plans. [ABSTRACT FROM AUTHOR]

Highlights: [•] Fluorocarbon/hydrocarbon surfactant mixtures show rich phase behavior. [•] Structural transitions from polyhedral vesicles to spherical vesicles occurred. [•] Crystallization was the main driving force for polyhedral vesicle formation. [•] Polyhedral vesicles show relatively high viscoelasticity. [ABSTRACT FROM AUTHOR]

Highlights: [•] GhCIPK6 is a novel cotton CBL-interacting protein kinase gene, exhibiting the same family signature. [•] GhCIPK6 was isolated from a RNA-Seq profile of stress-induced somatic embryogenesis in cotton. [•] Expression of the GhCIPK6 gene was induced by salt, drought and ABA treatments. [•] GhCIPK6-overexpression plant exhibited the tolerance to salt, drought and ABA stresses. [•] Overexpression of GhCIPK6 activated CBL/CIPK mediated stress response signalling pathways. [ABSTRACT FROM AUTHOR]

Abstract: In drug discovery, the occurrence of false positives is a major hurdle in the search for lead compounds that can be developed into drugs. A small-molecular-weight compound that inhibits dengue virus protease at low micromolar levels was identified in a screening campaign. Binding to the enzyme was confirmed by isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR). However, a structure–activity relationship study that ensued did not yield more potent leads. To further characterize the parental compound and its analogues, we developed a high-speed, low-cost, quantitative fluorescence quenching assay. We observed that specific analogues quenched dengue protease fluorescence and showed variation in IC50 values. In contrast, nonspecifically binding compounds did not quench its fluorescence and showed similar IC50 values with steep dose–response curves. We validated the assay using single Trp-to-Ala protease mutants and the competitive protease inhibitor aprotinin. Specific compounds detected in the binding assay were further analyzed by competitive ITC, NMR, and surface plasmon resonance, and the assay’s utility in comparison with these biophysical methods is discussed. The sensitivity of this assay makes it highly useful for hit finding and validation in drug discovery. Furthermore, the technique can be readily adapted for studying other protein–ligand interactions. [Copyright &y& Elsevier]

In present study, the antimicrobial compounds (AMCs) from Paecilomyces cicadae (P. cicadae) were initially purified, and its antimicrobial mechanism was investigated. The results showed that the molecular weight of AMCs in crude protein extracts was below 10 kDa. The minimum inhibitory concentration (MIC) of crude protein extracts against Escherichia coli (E. coli) was 0.050 mg/mL. After E. coli was treated by crude protein extracts, we found that it could disrupt the structure of cell membrane, change the content of whole-cell or membrane proteins. In addition, crude protein extracts with certain concentrations also could effectively interact with bacterial DNA. Quantitative real-time PCR (qRT-PCR) results indicated that the expression levels of flagellar biosynthesis genes fliP , fliO , flgD and flhB were down-regulated, whereas dppF and dnaJ which are associated with the transport across the membrane and the interaction with dnaK , respectively, were up-regulated when E. coli was exposed to crude protein extracts. The present findings suggested that AMCs from P. cicadae showed a potential value for the development of antibacterial products. • The antibacterial compounds were initially isolated from fermentation of P. cicadae. • One of the bactericidal mechanism from fermentation compounds was due to the change of cell structure. • The fermentation compounds could bind with cellular DNA, and affected the expression of related genes. [ABSTRACT FROM AUTHOR]

Di (2-ethylhexyl) phthalate (DEHP) is a known environmental endocrine disruptor that impairs development of testis and spermatogenesis. This study aims to explore the effects of STAT3/p53 and PI3K-Akt-mTOR signaling pathway on DEHP-induced reproductive toxicity in pubertal male rat. 24 6-week-old male Sprague-Dawley rats were randomly divided into 4 groups (Control, low-dose, middle-dose and high-dose group) and were treated with increasing concentration of DEHP (0, 250, 500, 1000 mg/kg/day) respectively for 28 consecutive days by intragastric administration. Our results showed that DEHP exposure induced obvious morphological changes of testis, decreased organ coefficient of testis and sperm count, and increased testicular cell apoptosis in the 500 and 1000 mg/kg/day DEHP groups (p <.05). The serum testosterone decreased in a dose-dependent manner after treatment with DEHP. Furthermore, the exposure of DEHP elevated the levels of oxidative stress accompanied by upregulated expression of p53 and reduced expression of STAT3. In addition, compared with the control group, the expression of PI3K, p-Akt and p-mTOR proteins significantly decreased, whereas the downstream autophagy-related proteins phosphorylated ULK1, Beclin-1, Atg7, LC3-II obviously increased in the 250 mg/kg/day DEHP group (p <.05). The expression of p62 was reduced in DEHP-treated groups. Our data indicated that autophagy could be activated to protect testes from DEHP-induced reproductive damage by inhibiting PI3K-Akt-mTOR signaling pathway in the 250 mg/kg/day DEHP group. STAT3/p53-mediated mitochondrial apoptosis pathway might play a major role to cause testis injury and reproductive dysfunction in the 500 and 1000 mg/kg/day DEHP groups. • DEHP induce reproductive toxicity in pubertal male rat. • Autophagy plays a protective role on rat testis injury exposed to low-dose DEHP. • Apoptosis plays a major role on rat reproductive damage exposed to high-dose DEHP. [ABSTRACT FROM AUTHOR]

Recent studies revealed that macrophages are polarized towards the M2 phenotype in an ovalbumin (OVA)-induced asthmatic model. Alveolar macrophages (AMs) are immune barriers in alveoli to various pathogens in the respiratory tract; AMs suppress Th2 cell proliferation, inhibit interleukin (IL)-4, IL-5, and IL-13 secretion, and protect against airway hyperresponsiveness in allergic asthma. However, the polarization status and effects of different types of AMs in the pathogenesis of asthma are not known. ATP/P2X7r, expressed mainly on macrophages and dendritic cells, is associated with acute and chronic asthmatic airway inflammation and Th2 immune responses in mice and humans and functions by activating the NLRP3 inflammasome complex and inducing proinflammatory cytokine release (IL-1β and IL-18). Therefore, we evaluated the association between the ATP/P2X7r axis and different types of AMs in the pathology of allergic asthma. A murine AM-depleted asthma model was established by administration of clodronate-encapsulated liposomes, and M1-or M2-AMs were adoptively transferred to confirm the effects of different AMs in allergic asthma. Brilliant Blue G and BzATP were administered to OVA/HDM-induced mice in vivo. Lipopolysaccharide + OVA, ATP, Brilliant Blue G, and BzATP were used to stimulate AMs isolated from control and asthmatic mice. We found that selective depletion of AMs aggravated lung inflammation in asthmatic mice. Further, M2-type AMs may play a key role in mediating asthmatic inflammatory responses via the adoptive transfer of M2-type AMs to AM-depleted asthmatic mice, and the phenotype of AMs differentiated to M2 type in asthma. P2X7r expression in M2-type AMs was higher than that in M1-type AMs. Activating P2X7r induced polarization of M2-type AMs and inhibited polarization of M1-type AMs, while blockage of P2X7r had the opposite effect. The ATP/P2X7r axis may participate in the pathogenesis of asthma by mediating the M2-type AM polarization. • M2-type AMs activate Th2 cell inflammatory response in allergic asthma. • The AM phenotype switches to M2 type in an OVA-induced asthmatic mice model. • M2-type alveolar macrophages preferentially express P2X7r. • The ATP/P2X7r axis induces M2-type and inhibits M1-type polarization of AMs. [ABSTRACT FROM AUTHOR]

The optimisation of land use allocation plays an important role in sustainable land use planning. It is crucial to realise the synergy between economic development and ecosystem conservation by optimising land use allocation. In this study, we developed a method to optimise land use allocation to balance ecosystem services and economic benefits based on the spatial difference of both ecosystem services value (ESV) and land use efficiency, based on the LAND System Cellular Automata model for Potential Effect (LANDSCAPE). In the optimisation model, spatial difference of ESV was represented by the parameter of resistance, while spatial difference of land use efficiency was expressed as the parameter of asynchronous rate of transition. Subsequently, land use allocation was optimised based on spatial difference of resistances and asynchronous rates. Taking Wuhan as the study area, the proposed optimisation model was used to conduct the optimisation of land use allocation during 2010–2020. Results showed that: economic benefits would increase by 444.77 million US$, while losses of ESV would decrease by 142.55 million US$ by optimisation of land use allocation. This indicated that the optimal allocation of land use based on spatial difference of ESV and land use efficiency can increase economic benefits at lower cost of ESV. In conclusion, it is feasible to allocate land resources to balance ecosystem services and economic benefits based on the differences of ESV and land use efficiency. This study highlights that taking the spatial difference of both ESV and land use efficiency into consideration is helpful for a sustainable land use planning. • Spatial difference of ESV and land use efficiency can be used to optimise land use. • ESV and economic benefits can be balanced by optimising land use allocation. • The LANDSCAPE model can be applied to optimise land use allocation. [ABSTRACT FROM AUTHOR]

A graphical abstract showing that Cryptotanshinone protected against pulmonary fibrosis through inhibition of both TGF-β/Smad and STAT3 signaling pathways. Cryptotanshinone (CTS), a lipophilic compound extracted from root of Salvia miltiorrhiza (Danshen), has demonstrated multiple pharmacological activities, including anti-inflammation, anti-proliferation and anti-infection. However, the effect of CTS on pulmonary fibrosis is unknown. This study aims to investigate the effects of CTS treatment on pulmonary fibrosis and its underlying mechanism. The pulmonary fibrosis model was established by intratracheal instillation of bleomycin (5 mg/kg) in Sprague-Dawley rats (in vivo) and stimulating human fetal lung fibroblasts (HLFs) with transforming growth factor-beta 1 (TGF-β1) (in vitro). CTS (7.5, 15, 30, 60 mg/kg/day) and pirfenidone (150 mg/kg/day, positive control) were administered by oral gavage for 28 days. In this study, we found CTS treatment improved pulmonary function, relieved pathological changes and attenuated the accumulation of extracellular matrix in pulmonary fibrosis rat model induced by bleomycin. Mechanistically, CTS suppressed phosphorylation of Smad2/3 and STAT3 induced by TGF-β1 in HLFs. Stattic, a 1-benzothiophene based small-molecule STAT3 inhibitor, resulted in a significant down-regulation of fibrosis biomarkers including fibronectin, collagen type I and alpha smooth muscle actin (α-SMA). Overexpression of STAT3 promoted expression of fibrosis biomarkers in HLFs cell model induced by TGF-β1 and partially blocked the inhibitory effect of CTS on TGF-β1-induced fibrosis response. Taken together, these results suggested that CTS protects against pulmonary fibrosis via inhibition of Smad and STAT3 signaling pathways. Thus, CTS may represent a promising drug candidate for treating pulmonary fibrosis. [ABSTRACT FROM AUTHOR]