Single-tube, single-strip lateral flow assays utilizing loop-mediated isothermal amplification for simultaneous hepatitis B and C viral detection.

Globally, hepatitis B virus (HBV) affects over 250 million people, whereas hepatitis C virus (HCV) affects approximately 70 million people, posing major public health challenges. Despite the availability of vaccines and treatments, a lack of comprehensive diagnostic coverage has left many cases undiagnosed and untreated. To address the need for sensitive, specific, and accessible diagnostics, this study introduced a multiplex loop-mediated isothermal amplification assay with lateral flow detection for simultaneous HBV and HCV testing. This assay achieved exceptional sensitivity and was capable of detecting HBV and HCV concurrently in a single tube and on a single strip within 25 min, achieving the required clinical sensitivity (10 and 103 genomic copies/reaction for HBV and HCV, respectively). The method was validated in clinical samples of various viral genotypes, achieving an equivalent limit of detection. Additionally, a custom portable heating device was developed for field use. The assay developed here, capable of direct viral detection on the strip, shows promise in supplanting current methods that solely identify antibodies and necessitate additional qPCR for viral activity assessment. This economical and rapid assay aligns with point-of-care testing needs, offering significant advancements in enhancing viral hepatitis diagnostics in settings with limited resources.

ß-aminoisobutyrics acid, a metabolite of BCAA, activates the AMPK/Nrf-2 pathway to prevent ferroptosis and ameliorates lung ischemia-reperfusion injury.

BACKGROUND: Lung ischemia-reperfusion (I/R) injury is a serious clinical problem without effective treatment. Enhancing branched-chain amino acids (BCAA) metabolism can protect against cardiac I/R injury, which may be related to bioactive molecules generated by BCAA metabolites. L-ß-aminoisobutyric acid (L-BAIBA), a metabolite of BCAA, has multi-organ protective effects, but whether it protects against lung I/R injury is unclear. METHODS: To assess the protective effect of L-BAIBA against lung I/R injury, an animal model was generated by clamping the hilum of the left lung, followed by releasing the clamp in C57BL/6 mice. Mice with lung I/R injury were pre-treated or post-treated with L-BAIBA (150 mg/kg/day), given by gavage or intraperitoneal injection. Lung injury was assessed by measuring lung edema and analyzing blood gases. Inflammation was assessed by measuring proinflammatory cytokines in bronchoalveolar lavage fluid (BALF), and neutrophil infiltration of the lung was measured by myeloperoxidase activity. Molecular biological methods, including western blot and immunofluorescence, were used to detect potential signaling mechanisms in A549 and BEAS-2B cells. RESULTS: We found that L-BAIBA can protect the lung from I/R injury by inhibiting ferroptosis, which depends on the up-regulation of the expressions of GPX4 and SLC7A11 in C57BL/6 mice. Additionally, we demonstrated that the Nrf-2 signaling pathway is key to the inhibitory effect of L-BAIBA on ferroptosis in A549 and BEAS-2B cells. L-BAIBA can induce the nuclear translocation of Nrf-2. Interfering with the expression of Nrf-2 eliminated the protective effect of L-BAIBA on ferroptosis. A screening of potential signaling pathways revealed that L-BAIBA can increase the phosphorylation of AMPK, and compound C can block the Nrf-2 nuclear translocation induced by L-BAIBA. The presence of compound C also blocked the protective effects of L-BAIBA on lung I/R injury in C57BL/6 mice. CONCLUSIONS: Our study showed that L-BAIBA protects against lung I/R injury via the AMPK/Nrf-2 signaling pathway, which could be a therapeutic target.

L-BAIBA upregulates the expression of GPX4 and SLC7A11 by activating the AMPK/Nrf-2/GPX4/SLC7A11 signaling pathway, thereby protecting against I/R-induced increase in ROS and ferroptosis in the lung.

Electric-field control of tri-state phase transformation with a selective dual-ion switch.

Materials can be transformed from one crystalline phase to another by using an electric field to control ion transfer, in a process that can be harnessed in applications such as batteries, smart windows and fuel cells. Increasing the number of transferrable ion species and of accessible crystalline phases could in principle greatly enrich material functionality. However, studies have so far focused mainly on the evolution and control of single ionic species (for example, oxygen, hydrogen or lithium ions). Here we describe the reversible and non-volatile electric-field control of dual-ion (oxygen and hydrogen) phase transformations, with associated electrochromic and magnetoelectric effects. We show that controlling the insertion and extraction of oxygen and hydrogen ions independently of each other can direct reversible phase transformations among three different material phases: the perovskite SrCoO3-δ (ref. 12), the brownmillerite SrCoO2.5 (ref. 13), and a hitherto-unexplored phase, HSrCoO2.5. By analysing the distinct optical absorption properties of these phases, we demonstrate selective manipulation of spectral transparency in the visible-light and infrared regions, revealing a dual-band electrochromic effect that could see application in smart windows. Moreover, the starkly different magnetic and electric properties of the three phases-HSrCoO2.5 is a weakly ferromagnetic insulator, SrCoO3-δ is a ferromagnetic metal, and SrCoO2.5 is an antiferromagnetic insulator-enable an unusual form of magnetoelectric coupling, allowing electric-field control of three different magnetic ground states. These findings open up opportunities for the electric-field control of multistate phase transformations with rich functionalities.

Effect of GRK4 on renal gastrin receptor regulation in hypertension.

OBJECTIVE: To investigate whether GRK4 regulates the phosphorylation and function of renal CCKBR. METHODS: GRK4 A142V transgenic mice were used as an animal model of enhanced GRK4 activity, and siRNA was used to silence the GRK4 gene to investigate the regulatory effect of GRK4 on CCKBR phosphorylation and function. Finally, the co-localization and co-connection of GRK4 and CCKBR in RPT cells were observed by laser confocal microscopy and immunoprecipitation to explore the mechanism of GRK4 regulating CCKBR. RESULTS: Gastrin infusion significantly increased urinary flow and sodium excretion rates in GRK4 WT mice (P < .05). GRK4 siRNA did not affect CCKBR protein expression in WKY RPT cells and SHR RPT cells, but remarkably reduced CCKBR phosphorylation in WKY and SHR RPT cells (P < .05). The inhibitory effect of gastrin on Na+-K+ -ATPase activity in WKY RPT cells was further enhanced by the reduction of GRK4 expression (P < .05), while GRK4 siRNA restored the inhibitory effect of gastrin on Na+-K+ -ATPase activity in SHR RPT cells. Laser confocal and Co-immunoprecipitation results showed that GRK4 and CCKBR co-localized in cultured RPT cells' cytoplasm. CONCLUSION: GRK4 participates in the development of hypertension by regulating the phosphorylation of renal CCKBR leading to impaired CCKBR function and water and sodium retention. Knockdown of GRK4 restored the function of CCKBR. The enhanced co-connection between GRK4 and CCKBR may be an important reason for the hyperphosphorylation of GRK4 and CCKBR involved in the pathogenesis of hypertension.

Numerical investigation of the blocking effect of a short duct on propeller noise.

Electric vertical and takeoff/landing vehicles for urban aerial mobility have attracted considerable attention in recent years. Some of these vehicles are equipped with ducted propellers to improve power efficiency, but the duct may also affect propeller noise generation and radiation. This work presents thorough numerical investigations to assess the importance of a short duct on propeller noise radiation. An analytical model is employed to predict noise emission from an isolated propeller, and the boundary element method is adopted to account for acoustic scattering effects. Additionally, an efficient data-clustering method is proposed to accelerate the overall noise prediction process. Parametric studies concerning geometries and the propeller's installation location are performed to exploit the duct's feasibility for low-noise vehicle development. Results suggest that the blocking effect can significantly benefit noise control for different rotating speeds, and installing the propeller at the symmetric plane of the duct can achieve the most noise reduction.

Evaluation of the Antioxidant Activities and Phenolic Profile of Shennongjia Apis cerana Honey through a Comparison with Apis mellifera Honey in China.

This study evaluates the phenolic profile as well as the antioxidant properties of Shennongjia Apis cerana honey through a comparison with Apis mellifera honey in China. The total phenolic content (TPC) ranges from 263 ± 2 to 681 ± 36 mg gallic acid/kg. The total flavonoids content (TFC) ranges from 35.9 ± 0.4 to 102.2 ± 0.8 mg epicatechin/kg. The correlations between TPC or TFC and the antioxidant results (FRAP, DPPH, and ABTS) were found to be statistically significant (p < 0.01). Furthermore, the phenolic compounds are quantified and qualified by high performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS), and a total of 83 phenolic compounds were tentatively identified in this study. A metabolomics analysis based on the 83 polyphenols was carried out and subjected to principal component analysis and orthogonal partial least squares-discriminant analysis. The results showed that it was possible to distinguish Apis cerana honey from Apis mellifera honey based on the phenolic profile.

Classification and review of free PCR primer design software.

MOTIVATION: Polymerase chain reaction (PCR) has been a revolutionary biomedical advancement. However, for PCR to be appropriately used, one must spend a significant amount of effort on PCR primer design. Carefully designed PCR primers not only increase sensitivity and specificity, but also decrease effort spent on experimental optimization. Computer software removes the human element by performing and automating the complex and rigorous calculations required in PCR primer design. Classification and review of the available software options and their capabilities should be a valuable resource for any PCR application. RESULTS: This article focuses on currently available free PCR primer design software and their major functions (https://pcrprimerdesign.github.io/). The software are classified according to their PCR applications, such as Sanger sequencing, reverse transcription quantitative PCR, single nucleotide polymorphism detection, splicing variant detection, methylation detection, microsatellite detection, multiplex PCR and targeted next generation sequencing, and conserved/degenerate primers to clone orthologous genes from related species, new gene family members in the same species, or to detect a group of related pathogens. Each software is summarized to provide a technical review of their capabilities and utilities.

B16F10 Cell Membrane-Based Nanovesicles for Melanoma Therapy Are Superior to Hyaluronic Acid-Modified Nanocarriers.

Some cancer cell membrane (CCM)-derived nanovesicles show strong homing effects and are used for targeted cancer therapy. By co-constructing the B16F10 cell membrane with a PEGylated phospholipid membrane, a new nanocarrier with a composite nanocrown structure was developed, which can evade immune recognition and actively target homologous melanoma. The nanocrowns have an encapsulation efficiency of more than 90% for paclitaxel and showed no significant difference (p > 0.05) from the PEGylated phospholipid membrane vesicles. Compared with the hyaluronic acid-modified PEGylated phospholipid membrane vesicles, the biomimetic nanocrowns enhanced the escape of nanovesicles from reticuloendothelial cells in vitro and extended the circulation time in vivo; moreover, the nanocrowns showed superior melanoma-targeted drug delivery capability and improved anticancer effects of paclitaxel as demonstrated by the inhibition of B16F10 cell proliferation and induction of apoptosis by interfering with microtubule formation. In contrast, the modification of hyaluronic acid did not increase the targeting capacity or antitumor effects of the nanocrowns, confirming that the superior targeting capacity was mediated by the exposed homologous CCMs rather than by hyaluronic acid. Our results demonstrate the potential of using biomimetic nanocrowns for active melanoma-targeted therapy.

Low-dose dexmedetomidine as a perineural adjuvant for postoperative analgesia: a randomized controlled trial.

PURPOSE: Dexmedetomidine has been proposed as an additive to local anesthetics to prolong peripheral nerve block duration; however, perineural dexmedetomidine has been associated with an increased risk of bradycardia and hypotension This randomized controlled study investigated the effects of low-dose dexmedetomidine as a perineural adjuvant for postoperative analgesia. METHODS: Fifty-five patients who had undergone elective upper extremity surgery were randomized to receive an ultrasound-guided supraclavicular brachial plexus block with 20 mL 0.5% ropivacaine with or without 30 µg dexmedetomidine. The primary outcome was the duration of analgesia. Secondary outcomes included the onset time and duration of the motor and sensory blocks, incidence of hypotension and bradycardia, total postoperative analgesics, and safety assessment during the 24 h after surgery. RESULTS: Dexmedetomidine significantly prolonged the duration of analgesia (887 ± 92 min vs 661 ± 83 min, P < 0.0001). The onset time and the duration of motor and sensory block were significantly different between the groups (all P < 0.001). No episodes of hypotension or bradycardia were detected in the dexmedetomidine group. The total postoperative analgesic use and side effect profiles in the first 24 h postoperative period were similar for both groups. CONCLUSIONS: Low-dose dexmedetomidine (30 µg) as a perineural adjuvant significantly prolonged the analgesic duration of a brachial plexus block without inducing hemodynamic instability. TRIAL REGISTRATION: This trial was registered at ClinicalTrial.gov (NCT02630290).

Recognizing the aeroacoustic information of noise radiated by an unflanged duct based on convolutional neural networks.

Accurately recognizing the aeroacoustic information of noise propagating into and radiating out of an aero-engine duct is of both fundamental and practical interest. The aeroacoustic information includes (1) the acoustic properties of the noise source, such as the frequency (f) and the circumferential and radial mode numbers (m, n), and (2) the flight conditions, including the ambient flow speed (M0) and the jet flow speed (M1). In this study, a data-driven model is developed to predict the aeroacoustic information of a simplified aero-engine duct noise from the far-field sound pressure level directivity. The model is constructed by the integration of one-dimensional convolutional layers and fully connected layers. The training and validation datasets are calculated from the analytical model for noise radiation from a semi-infinite unflanged duct based on the Wiener-Hopf method. For a single-spinning mode source, a regression model is established for f, M0, and M1 prediction, and a classification model is built up for m and n prediction. Additionally, for a multi-spinning mode source, the regression model is used to predict the coefficient of each mode. Results show that the proposed data-driven model can effectively and robustly predict the acoustic characteristics of noise propagation in and radiation out of an aero-engine bypass duct.

Cooperative game theory approach to develop an incentive mechanism for biopesticide adoption through farmer producer organizations.

Biopesticides have been recognized as viable alternatives to chemical pesticides in controlling agricultural pests for plants and reducing harmful chemical residues. However, small and marginal farmers are facing challenges while adopting biopesticides, namely, high cost and complicated application techniques, resulting in a low level of farmer acceptance. Accordingly, Farmer Producer Organizations (FPOs), voluntarily formed by farmers, develop mutual technical assistance among their members to solve the technical problems of biopesticide adoption. This study assumes that as a new form of farmer cooperative, FPOs have the potential to promote biopesticide adoption through the implementation of collective pesticide adoption (CPA). Along this line, this paper uses a cooperative game-based hybrid method to develop an incentive mechanism of biopesticide adoption for FPOs to implement CPAs. First, we construct a CPA decision model for mixed pesticides (i.e., biopesticides and chemical pesticides) based on multichoice goal programming (MCGP) to compromise the conflicting objectives regarding cost efficiency and chemical residue reduction, thereby obtaining the optimal total cost of pesticide adoption. Second, recognizing the optimal total adoption cost as a baseline, we devise a cooperative game-based cost allocation scheme to maintain farmers' voluntary participation in FPOs. This study demonstrates that the CPA implemented based on our proposed models can at least match if not surpass the economic and environmental performance of farmers' independent pesticide adoption (IPA). We further demonstrate that the proposed cooperative game solution is more suitable for the FPO's cost allocation issue than the eminent solutions, such as the Shapley value.

Gastrin, via activation of PPARα, protects the kidney against hypertensive injury.

Hypertensive nephropathy (HN) is a common cause of end-stage renal disease with renal fibrosis; chronic kidney disease is associated with elevated serum gastrin. However, the relationship between gastrin and renal fibrosis in HN is still unknown. We, now, report that mice with angiotensin II (Ang II)-induced HN had increased renal cholecystokinin receptor B (CCKBR) expression. Knockout of CCKBR in mice aggravated, while long-term subcutaneous infusion of gastrin ameliorated the renal injury and interstitial fibrosis in HN and unilateral ureteral obstruction (UUO). The protective effects of gastrin on renal fibrosis can be independent of its regulation of blood pressure, because in UUO, gastrin decreased renal fibrosis without affecting blood pressure. Gastrin treatment decreased Ang II-induced renal tubule cell apoptosis, reversed Ang II-mediated inhibition of macrophage efferocytosis, and reduced renal inflammation. A screening of the regulatory factors of efferocytosis showed involvement of peroxisome proliferator-activated receptor α (PPAR-α). Knockdown of PPAR-α by shRNA blocked the anti-fibrotic effect of gastrin in vitro in mouse renal proximal tubule cells and macrophages. Immunofluorescence microscopy, Western blotting, luciferase reporter, and Cut&tag-qPCR analyses showed that CCKBR may be a transcription factor of PPAR-α, because gastrin treatment induced CCKBR translocation from cytosol to nucleus, binding to the PPAR-α promoter region, and increasing PPAR-α gene transcription. In conclusion, gastrin protects against HN by normalizing blood pressure, decreasing renal tubule cell apoptosis, and increasing macrophage efferocytosis. Gastrin-mediated CCKBR nuclear translocation may make it act as a transcription factor of PPAR-α, which is a novel signaling pathway. Gastrin may be a new potential drug for HN therapy.

An investigation on noise attenuation by acoustic liner constructed by Helmholtz resonators with extended necks.

The noise attenuation properties of an acoustic liner consisting of Helmholtz resonators with extended necks (HRENs) are investigated. An optimal liner constructed by 16 inhomogeneous HRENs is designed to be effective in sound absorption in a prescribed frequency range from 700 to 1000 Hz. Its quasi-perfect absorption capability (average absorption coefficient above 0.9) is validated by measurements and simulations. The resonance frequencies of the individual resonators in the designed liner are just located within the effective absorption bandwidth, indicating the overlapping phenomenon of absorption peaks. In addition, the liner maintains a thin thickness, about 1/25th with respect to the longest operating wavelengths. To assess the acoustic performance of the designed liner in the presence of mean flow, experimental investigations are performed in a flow tube. Results show a near flat transmission loss is attained in the target frequency range by the designed liner. Additionally, the impedance of the uniform HREN-based liner is extracted at flow condition. In all, the inhomogeneous HREN-based liner is featured by the thin thickness and the excellent wide-band noise attenuation property. These features make the designed liner an promising solution for noise attenuation in both static and flow conditions.

An extra-broadband compact sound-absorbing structure composing of double-layer resonator with multiple perforations.

Based on multi-layer Helmholtz resonators with extended necks (HREN), a compact sound-absorbing structure is developed for extra-broadband sound absorption. The structure of HREN with a single perforation is beneficial for low-frequency absorption under a thin thickness. However, it faces the problem of effectively attenuating noise only within a narrow frequency bandwidth near the resonance frequency. To widen its effective absorption bandwidth, two potential solutions are proposed and evaluated: (1) increasing the perforation number, and (2) adding extra layers in series. Results reveal that more perforations produce a wider half-absorption bandwidth, and the added layers induce more absorption peaks. Thus, a multi-layer HREN unit with multiple perforations is a favorable candidate for broadband sound absorption. On the basis of these, we design a broadband acoustic structure constructed by 11 coupled parallelly arranged double-layer HREN units with multiple perforations. The structure possesses an average sound-absorption coefficient of 0.9 in a prescribed frequency ranging from 800 to 3000 Hz. The absorption effectiveness of the structure is validated via experiments. What is more, the dimension of the absorber is only 50 mm (long)×50 mm (width)×41 mm (depth), indicating its compact characteristic. Hence, the developed extra broadband and compact sound-absorbing structure possesses a promising potential in various engineering applications.

Molecular characterization of a RNA polymerase (RNAP) II (DNA directed) polypeptide H (POLR2H) in Pacific white shrimp (Litopenaeus vannamei) and its role in response to high-pH stress.

RNA polymerase (RNAP) II (DNA-directed) (POLR2) genes are essential for cell viability under environmental stress and for the transfer of biological information from DNA to RNA. However, the function and characteristics of POLR2 genes in crustaceans are still unknown. In the present study, a POLR2H cDNA was isolated from Pacific white shrimp (Litopenaeus vannamei) and designated as Lv-POLR2H. The full-length Lv-POLR2H cDNA is 772 bp in length and contains a 32-bp 5'- untranslated region (UTR), a 284-bp 3'- UTR with a poly (A) sequence, and an open reading frame (ORF) of 456 bp encoding an Lv-POLR2H protein of 151 amino acids with a deduced molecular weight of 17.21 kDa. The Lv-POLR2H protein only contains one functional domain, harbors no transmembrane domains and mainly locates in the nucleus. The expression of the Lv-POLR2H mRNA was ubiquitously detected in all selected tissues, with the highest level in the gills. In situ hybridization (ISH) analysis showed that Lv-POLR2H was mainly located in the secondary gill filaments, the transcript levels of Lv-POLR2H in the gills were found to be significantly affected after challenge by pH, low salinity and high concentrations of NO2- and NH4+, indicating that Lv-POLR2H in gill tissues might play roles under various physical stresses. Specifically, under high-pH stress, knockdown of Lv-POLR2H via siRNA significantly decreased the survival rate of the shrimp, indicating its key roles in the response to high-pH stress. Our study may provide the first evidence of the role of POLR2H in shrimp responding to high-pH stress and provides new insight into molecular regulation in response to high pH in crustaceans.

Galectin-3 Induces Atrial Fibrosis by Activating the TGF-ß1/Smad Pathway in Patients with Atrial Fibrillation.

BACKGROUND: Atrial fibrosis plays a critical role in the occurrence and maintenance of atrial fibrillation. The role of TGF-ß1 in mediating atrial fibrosis is well documented. The ß-galactoside-binding lectin galectin-3 (Gal-3) is mainly produced by macrophages in biological events such as inflammation and angiogenesis. Previous studies have shown that Gal-3 is associated with atrial fibrosis, but the relationship between TGF-ß1 and Gal-3 in atrial fibrosis remains unclear. OBJECTIVE: To determine whether Gal-3 induces atrial fibrosis and atrial fibrillation by activating the TGF-ß1/Smad pathway and whether the expression of Gal-3 is mediated by TGF-ß1, which can enable assessing the relationship between Gal-3 and TGF-ß1 in atrial fibrosis. METHODS: In this study, 30 patients' right atrial appendages were collected and divided into 3 groups: congenital heart disease sinus rhythm group (n = 10, as a control group), rheumatic heart disease sinus rhythm group (n = 10), and rheumatic heart disease atrial fibrillation group (n = 10). Rat atrial fibroblasts were cultured in vitro, and recombinant Gal-3 and recombinant TGF-ß1 proteins were added to the cell culture. The expression of Gal-3, TGF-ß1, Smad2, and collagen I was detected by Western blotting and quantitative real-time PCR. Atrial tissues were stained with Masson's trichrome stain to evaluate the extent of atrial fibrosis. The expression of Gal-3 and TGF-ß1 was detected by immunohistochemical staining and immunofluorescence staining. Gal-3 and TGF-ß1 interaction was demonstrated by immunoprecipitation. RESULTS: The expression levels of Gal-3, TGF-ß1, Smad2, and collagen I were elevated in the rheumatic heart disease atrial fibrillation group compared with the congenital heart disease sinus rhythm group and the rheumatic heart disease sinus rhythm group. In cultured atrial fibroblasts, there is a synergistic interaction between Gal-3 and TGF-ß1. Gal-3 stimulated the TGF-ß1/Smad pathway, and overexpression of TGF-ß1 induced Gal-3 expression. CONCLUSIONS: Gal-3 and TGF-ß1 interact with each other and stimulate the downstream TGF-ß1/Smad pathway. This finding suggests that Gal-3 could be an important factor in TGF-ß1-induced fibrosis in atrial fibrillation.

Level-set based topology optimization on acoustic balcony ceiling design of a simplified urban building for noise reduction.

Balconies can provide noise shielding for residents who live in high-rise apartment buildings. The efficiency of noise reduction induced by a balcony largely depends on the shape of the balcony ceiling. This study aims to optimize the shape of the ceiling of a two-dimensional simplified urban building to enhance noise mitigation by using level-set based topology optimization, which is capable of providing a distinct and smooth interface. Noise sources at both single and multi-frequency optimization are considered. In the single-frequency optimization, two peak frequencies in the spectrum of sound pressure level (SPL) at receivers on the fourth floor of an ordinary ceiling are selected. Results show that significant SPL reduction is attained by the optimized ceiling. In addition, broadband noise suppression at frequencies above the target value is also achieved. The underlying mechanism is that the optimized ceiling consisting of several concaves can redirect the incident wave propagating away from the balcony and effectively avoid forming a trapped mode within the area between the floor and the ceiling. Additionally, more effective noise reduction is achieved by the multi-frequency optimization. Thus, the proposed design strategy can be widely used in various applications of noise reduction in the field of building and environment.

Potential role of MG53 in the regulation of transforming-growth-factor-ß1-induced atrial fibrosis and vulnerability to atrial fibrillation.

Atrial fibrosis plays a critical role in atrial fibrillation (AF) by the transforming growth factor (TGF)-ß1/Smad pathway. The disordered differentiation, proliferation, migration and collagen deposition of atrial fibroblasts play significant roles in atrial fibrosis. Mitsugumin (MG)53 is predominantly expressed in myocardium of rodents and has multiple biological functions. However, the role of MG53 in cardiac fibrosis remains unclear. This study provided clinical and experimental evidence for the involvement of MG53 in atrial fibrosis in humans and atrial fibrosis phenotype in cultured rat atrial fibroblasts. In atrial tissue from patients we demonstrated that MG53 was expressed in human atrium. Expression of MG53 increased with the extent of atrial fibrosis, which could induce AF. In cultured atrial fibroblasts, depletion of MG53 by siRNA caused down-regulation of the TGF-ß1/Smad pathway, while overexpression of MG53 by adenovirus up-regulated the pathway. MG53 regulated the proliferation and migration of atrial fibroblasts. Besides, exogenous TGF-ß1 suppressed expression of MG53. In conclusion, we demonstrated that MG53 was expressed in human atrium, and may be a potential upstream of the TGF-ß1/Smad pathway in human atrium and rat atrial fibroblasts. This suggests that MG53 is a potential regulator of atrial fibrosis induced by the TGF-ß1/Smad pathway in patients with AF.

Transcriptomic and physiological changes in western mosquitofish (Gambusia affinis) after exposure to norgestrel.

Norgestrel (NGT) is a synthetic progestin used in human and veterinary medicine. Adult female mosquitofish were exposed to NGT for 42 d at 377 ng L-1. The fin morphology and the liver transcriptome were assessed. NGT exposure increased ray 4:6 length ratio. As compared to the control, NGT treatment affected the expression of 11,772 annotated transcripts in female mosquitofish. Specifically, we found 5780 were repressed while 5992 were significantly induced. Gene ontology (GO) analysis showed that 53 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways and 158 GO terms were significantly over expressed. Genes showing the largest magnitude of expression changes were related to fin development, androgen biosynthesis, and lipid and fatty acid metabolisms, suggesting the involvement of these biological processes in response to NGT exposure in G. affinis. This first comprehensive study on the transcriptomic alterations by NGT in G. affinis not only provides valuable information on the development of molecular markers but also opens new avenues for studies on the molecular mechanisms of effects of NGT in particular and possibly other progestins in G. affinis.

By suppressing the expression of anterior pharynx-defective-1α and -1ß and inhibiting the aggregation of ß-amyloid protein, magnesium ions inhibit the cognitive decline of amyloid precursor protein/presenilin 1 transgenic mice.

Alzheimer's disease (AD) is associated with a magnesium ion (Mg(2+)) deficit in the serum or brain. However, the mechanisms regulating the roles of Mg(2+) in the pathologic condition of AD remain unknown. We studied whether brain Mg(2+) can decrease ß-amyloid (Aß) deposition and ameliorate the cognitive decline in a model of AD, the APPswe/PS1DE9 transgenic (Tg) mouse. We used a recently developed compound, magnesium-L-threonate (MgT), for a treatment that resulted in enhanced clearance of Aß in an anterior pharynx-defective (APH)-1α/-1ß-dependent manner. To further explore how MgT treatment inhibits cognitive decline in APP/PS1 Tg mice, the critical molecules for amyloid precursor protein (APP) cleavage and signaling pathways were investigated. In neurons, ERK1/2 and PPARγ signaling pathways were activated by MgT treatment, which in turn suppressed (by >80%) the expression of APH-1α/-1ß, which is responsible for the deposition of Aß and potentially contributes to the memory deficit that occurs in AD. More important, Aß oligomers in the cerebrospinal fluid (CSF) further promoted the expression of APH-1α/-1ß (by >2.5-fold), which enhances the γ-cleavage of APP and Aß deposition during AD progression. These findings provide new insights into the mechanisms of AD progression and are instrumental for developing better strategies to combat the disease.