Promiscuous Oxidosqualene Cyclases from Neoalsomitra integrifoliola Catalyzing the Formation of Tetracyclic, Pentacyclic, and Heterocyclic Triterpenes.

Six oxidosqualene cyclases (NiOSC1-NiOSC6) from Neoalsomitra integrifoliola were characterized for the biosynthesis of diverse triterpene scaffolds, including tetracyclic and pentacyclic triterpenes from the 2,3-oxidosqualene (1) and oxacyclic triterpenes from the 2,3:22,23-dioxidosqualene (2). NiOSC1 showed high efficiency in the production of naturally rare (20R)-epimers of oxacyclic triterpenes. Mutagenesis results revealed that the NiOSC1-F731G mutant significantly increased the yields of (20R)-epimers compared to the wild type. Homology modeling and molecular docking elucidated the origin of the (20R)-configuration in the epoxide addition step.

Efficacy and safety of modified Valsalva maneuver for treatment of paroxysmal supraventricular tachycardia: a meta-analysis.

OBJECTIVE: To compare the efficacy and safety of the modified versus standard Valsalva maneuver in the treatment of paroxysmal supraventricular tachycardia (PSVT). METHODS: The PubMed, Embase, Web of Science, CNKI, WanFang Data, and VIP electronic databases were searched to identify studies comparing the modified and standard Valsalva maneuvers in the treatment of PSVT from database inception to 1 May 2023. Two reviewers independently screened the literature, extracted the data, and assessed the risk of bias of all included studies. RESULTS: Nineteen randomized controlled trials involving 2527 patients with PSVT were included. The overall rate of cardioversion was higher in the modified than standard Valsalva group (risk ratio [RR] = 1.80, 95% confidence interval [CI] = 1.61-2.01), as was the success rate of cardioversion after a single Valsalva maneuver (RR = 2.05, 95% CI = 1.74-2.41). There was no statistically significant difference in adverse reactions between the two groups (RR = 1.07, 95% CI = 0.82-1.38). CONCLUSION: Current evidence suggests that the modified Valsalva maneuver can significantly improve the success rate of cardioversion in patients with PSVT without increasing adverse reactions. The modified Valsalva maneuver is therefore worth promoting and should be considered as a routine first treatment.INPLASY registration number: 2023100092.

The value of metagenomic next-generation sequencing for the diagnosis of pulmonary tuberculosis using bronchoalveolar lavage fluid.

OBJECTIVE: The aim of this study was to compare metagenomic next-generation sequencing (mNGS) with other methods, including Xpert MTB/RIF, Mycobacterium tuberculosis (MTB) culture, and acid-fast bacillus (AFB) staining in the diagnosis of pulmonary tuberculosis (PTB) using bronchoalveolar lavage fluid (BALF). METHODS: The data of 186 patients with suspected PTB were retrospectively collected from January 2020 to May 2021 at Tongji Hospital. BALF samples were collected from all patients and analyzed using AFB staining, MTB culture, Xpert MTB/RIF, and mNGS. RESULTS: Of the 186 patients, 38 patients were ultimately diagnosed as PTB. Metagenomic next-generation sequencing exhibited a sensitivity of 78.95%, which was higher than AFB staining (27.59%) and MTB culture (44.12%) but similar to Xpert MTB/RIF (72.73%). Utilization of combined methods demonstrates improvement for PTB diagnosis. In support of this, the area under the receiver operating characteristic curve for the combination of mNGS and MTB culture (0.933, 95% CI: 0.871, 0.995) was larger than those of mNGS, Xpert MTB/RIF, MTB culture, and the combination of Xpert MTB/RIF and MTB culture. CONCLUSION: The sensitivity of mNGS in the diagnosis of PTB using BALF specimen is similar to Xpert MTB/RIF. Metagenomic next-generation sequencing in combination with MTB culture may further improve the diagnosis of pulmonary tuberculosis.

Insertion/deletion polymorphism for genetic background and forensic performance exploration of the Sui group from Guizhou.

Insertion/deletion polymorphisms (InDels) as ideal genetic markers for forensic genetics are appreciated by scholars both nationally and internationally because they integrated the favorable features of single nucleotide polymorphisms (SNPs) and short tandem repeats (STRs). Nevertheless, with the limited identification efficiency of InDels, the multiplex amplification systems of InDels might just be applied as the supplementary methods in paternity testing with respect to commonly used STRs. In the current research, we successfully genotyped 105 unrelated individuals from the Guizhou Sui population based on a six-color fluorescence multiplex panel that could simultaneously detect 64 genetic markers (59 autosomal InDels, two autosomal miniSTRs and three Y chromosomal genetic markers). In addition, frequency distributions and forensic statistical parameters of these loci in the Sui group were assessed using the STRAF software. Phylogenetic relationships among the Sui group and other reference populations were dissected by two methods (principal component analysis and phylogenetic trees) based on 59 InDels. The combined discrimination power and probability of exclusion values of 61 autosomal genetic markers in the Sui group were nearly equal to 1-1.90063 × 10-27 and 0.999998272, respectively. Furthermore, we observed that the Sui group from Guizhou had closer genetic affinities with East Asian populations with respect to other continental populations. In summary, we stated that the multiplex amplification system might be utilized as a prospective independent tool for human individual identification and parentage testing in the Sui group residing in Guizhou.

A Randomized Controlled Trial to Compare Peripherally Inserted Central Catheter Tunnel Lengths in Adult Patients With Cancer.

BACKGROUND: Evidence is insufficient on the effect of tunnel lengths on tunneled peripherally inserted central catheter (PICC) placement in adult patients with cancer. OBJECTIVES: The primary objective was to explore whether there is an optimal PICC tunnel length to reduce the risk of PICC-related complications. The secondary objective was to compare patients' pain and comfort levels during catheter placement with different tunnel lengths. METHODS: Two hundred patients were randomly assigned to groups based on PICC tunnel length. Data collected included baseline characteristics, catheter-related characteristics, PICC-related complications, and patients' pain and comfort levels. FINDINGS: Patients with 4 cm, 5 cm, and 6 cm PICC tunnel lengths had a longer catheter dwell time and fewer PICC-related complications. No significant differences were found among all groups regarding patients' pain and comfort levels. The results suggest that a tunneled PICC is safe and effective. A tunnel length longer than 4 cm is recommended for tunneled PICC placement.

Mitochondria dysfunction in airway epithelial cells is associated with type 2-low asthma.

Background: Type 2 (T2)-low asthma can be severe and corticosteroid-resistant. Airway epithelial cells play a pivotal role in the development of asthma, and mitochondria dysfunction is involved in the pathogenesis of asthma. However, the role of epithelial mitochondria dysfunction in T2-low asthma remains unknown. Methods: Differentially expressed genes (DEGs) were identified using gene expression omnibus (GEO) dataset GSE4302, which is originated from airway epithelial brushings from T2-high (n = 22) and T2-low asthma patients (n = 20). Gene set enrichment analysis (GSEA) was implemented to analyze the potential biological pathway involved between T2-low and T2-high asthma. T2-low asthma related genes were identified using weighted gene co-expression network analysis (WGCNA). The mitochondria-related genes (Mito-RGs) were referred to the Molecular Signatures Database (MSigDB). T2-low asthma related mitochondria (T2-low-Mito) DEGs were obtained by intersecting the DEGs, T2-low asthma related genes, and Mito-RGs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed to further explore the potential function of the T2-low-Mito DEGs. In addition, the hub genes were further identified by protein-protein interaction (PPI), and the expressions of hub genes were verified in another GEO dataset GSE67472 and bronchial brushings from patients recruited at Tongji Hospital. Results: Six hundred and ninety-two DEGs, including 107 downregulated genes and 585 upregulated genes were identified in airway epithelial brushings from T2-high and T2-low asthma patients included in GSE4302 dataset. GSEA showed that mitochondrial ATP synthesis coupled electron transport is involved in T2-low asthma. Nine hundred and four T2-low asthma related genes were identified using WGCNA. Twenty-two T2-low-Mito DEGs were obtained by intersecting the DEGs, T2-low asthma and Mito-RGs. The GO enrichment analysis of the T2-low-Mito DEGs showed significant enrichment of mitochondrial respiratory chain complex assembly, and respiratory electron transport chain. PPI network was constructed using 22 T2-low-Mito DEGs, and five hub genes, ATP5G1, UQCR10, NDUFA3, TIMM10, and NDUFAB1, were identified. Moreover, the expression of these hub genes was validated in another GEO dataset, and our cohort of asthma patients. Conclusion: This study suggests that mitochondria dysfunction contributes to T2-low asthma.

Functional Renormalization Group Study of Superconductivity in Rhombohedral Trilayer Graphene.

We employ a functional renormalization group approach to ascertain the pairing mechanism and symmetry of the superconducting phase observed in rhombohedral trilayer graphene. Superconductivity in this system occurs in a regime of carrier density and displacement field with a weakly distorted annular Fermi sea. We find that repulsive Coulomb interactions can induce electron pairing on the Fermi surface by taking advantage of momentum-space structure associated with the finite width of the Fermi sea annulus. The degeneracy between spin-singlet and spin-triplet pairing is lifted by valley-exchange interactions that strengthen under the RG flow and develop nontrivial momentum-space structure. We find that the leading pairing instability is d-wave-like and spin singlet, and that the theoretical phase diagram versus carrier density and displacement field agrees qualitatively with experiment.

Exosomal miR-196a-5p enhances radioresistance in lung cancer cells by downregulating NFKBIA.

Radiation therapy is recognized as an effective modality in the treatment of lung cancer, but radioresistance resulting from prolonged treatment reduces the chances of recovery. MicroRNAs (miRNAs) play a pivotal role in radiotherapy immunity. In this study, we aimed to investigate the mechanism by which miR-196a-5p affects radioresistance in lung cancer. The radioresistant lung cancer cell line A549R26-1 was established by radiation treatment. Cancer-associated fibroblasts (CAFs) and normal fibroblasts (NFs) were observed by microscopy, and the expression levels of CAF-specific marker proteins were detected by immunofluorescence. The shape of the exosomes was observed by electron microscopy. A CCK-8 assay was used to detect cell viability, while clone formation assays were used to detect cell proliferative capacity. Flow cytometry was performed to investigate apoptosis. The binding of miR-196a-5p and NFKBIA was predicted and further verified by the dual luciferase reporter experiment. qRT-PCR and western blotting were used to detect gene mRNA and protein levels. We found that exosomes secreted by CAFs could enhance lung cancer cell radioresistance. Moreover, miR-196a-5p potentially bound to NFKBIA, promoting malignant phenotypes in radioresistant cells. Furthermore, exosomal miR-196a-5p derived from CAFs increased radiotherapy immunity in lung cancer. Exosomal miR-196a-5p derived from CAFs enhanced radioresistance in lung cancer cells by downregulating NFKBIA, providing a new potential target for the treatment of lung cancer.

Identifying the impact of the Zone Insertion MethodTM (ZIMTM): A randomized controlled trial.

BACKGROUND: In 2011, Dawson proposed the Zone Insertion MethodTM (ZIMTM) to identify the optimal peripherally inserted central catheters (PICCs) insertion site in the upper arm. However, data on the effectiveness and safety of the ZIMTM in guiding PICC placement in Chinese population is limited. METHODS: In this randomized controlled trial, 120 cancer patients were randomly assigned to the upper portion of the red zone (RZ), the green zone (GZ) and the lower portion of the yellow zone (YZ) groups (at a 1:1:1 ratio). The aim was to compare the degree of patient comfort and the incidence of major PICC complications among the three insertion zones based on the ZIMTM in a Chinese Cancer Center. (Clinical Trials. Gov number, ChiCTR1900024111). RESULTS: A total of 118 catheters were inserted in 118 patients (2 patients were lost to follow-up). After the 1-month follow-up, patients randomly assigned to the YZ group had a higher degree of comfort with a lower score than those assigned to the other two zone groups: 30.21±3.16 in the YZ group versus 31.65±2.51 in the RZ group and 31.59±2.92 in the GZ group (P=.046). The incidence of thrombosis (10/40, 25%) and occlusion (4/40, 10%) in the RZ, which were significantly higher than those in the other two zone groups (χ2 =7.368, P=.02; χ2 =5.778, P =.03), whereas the risk in the GZ group was similar to that in the YZ group. The incidence of contact dermatitis in the GZ group was significantly higher than that of the other two zone groups (χ2=12.873, P=.001). CONCLUSIONS: This study found that the lower portion of YZ seems to be another suitable PICC insertion site for a higher degree of comfort and a lower risk of occlusion and thrombosis, which broadens the choice of PICC insertion sites in the upper arm for clinical practice.

Pseudospin Paramagnons and the Superconducting Dome in Magic Angle Twisted Bilayer Graphene.

We present a theory of superconductivity in twisted bilayer graphene in which attraction is generated between electrons on the same honeycomb sublattice when the system is close to a sublattice polarization instability. The resulting Cooper pairs are spin-polarized valley singlets. Because the sublattice polarizability is mainly contributed by interband fluctuations, superconductivity occurs over a wide range of filling fraction. It is suppressed by (i) applying a sublattice polarizing field (generated by an aligned BN substrate) or (ii) changing moiré band filling to favor valley polarization. The enhanced intrasublattice attraction close to sublattice polarization instability is analogous to enhanced like-spin attraction in liquid ^{3}He near the melting curve and the enhanced valley-singlet repulsion close to valley-polarization instabilities is analogous to enhanced spin-singlet repulsion in metals that are close to a ferromagnetic instability. We comment on the relationship between our pseudospin paramagnon model and the rich phenomenology of superconductivity in twisted bilayer and multilayer graphene.

Comprehensive characterization and optimization of Caco-2 cells enabled the development of a miniaturized 96-well permeability assay.

Assessment of compound permeability through a Caco-2 cell monolayer is a well-accepted model to evaluate its in-vivo permeability potential and transporter interaction. While this assay has commonly been conducted using a 24-well assay plate format, a miniaturised 96-well assay format is highly desirable to achieve greater capacity and higher efficiency.Previous attempts to convert this assay from 24-well to 96-well format at our lab, however, had met with varied efflux capacities and unacceptable efflux ratios for digoxin, a substrate of P-glycoprotein (Pgp), which indicated inadequate Pgp transporter expression in the 96-well format.These challenges in converting the assays were attributed to the heterogeneous and unstable nature of the Caco-2 cells. To overcome the challenges, single-cell sorting of Caco-2 cells was conducted by flow cytometry to obtain a more homogeneous and stable cell population. The sorted cells were then seeded to 96-well transwell plates and the Pgp expression under various cell culture conditions was monitored by a LC-MS/MS-based targeted proteomics method.Through cell sorting and direct Pgp expression measurement, Caco-2 cells with adequate and sustained Pgp expression in a 96-well format were obtained, which led to the successful development and implementation of a 96-well Caco-2 assay with significant efficiency gain and faster turnaround time than the historical 24-well assay.

Synchronization of spatially discordant voltage and calcium alternans in cardiac tissue.

The heart is an excitable medium which is excited by membrane potential depolarization and propagation. Membrane potential depolarization brings in calcium (Ca) through the Ca channels to trigger intracellular Ca release for contraction of the heart. Ca also affects voltage via Ca-dependent ionic currents, and thus, voltage and Ca are bidirectionally coupled. It has been shown that the voltage subsystem or the Ca subsystem can generate its own dynamical instabilities which are affected by their bidirectional couplings, leading to complex dynamics of action potential and Ca cycling. Moreover, the dynamics become spatiotemporal in tissue in which cells are diffusively coupled through voltage. A widely investigated spatiotemporal dynamics is spatially discordant alternans (SDA) in which action potential duration (APD) or Ca amplitude exhibits temporally period-2 and spatially out-of-phase patterns, i.e., APD-SDA and Ca-SDA patterns, respectively. However, the mechanisms of formation, stability, and synchronization of APD-SDA and Ca-SDA patterns remain incompletely understood. In this paper, we use cardiac tissue models described by an amplitude equation, coupled iterated maps, and reaction-diffusion equations with detailed physiology (the ionic model) to perform analytical and computational investigations. We show that, when the Ca subsystem is stable, the Ca-SDA pattern always follows the APD-SDA pattern, and thus, they are always synchronized. When the Ca subsystem is unstable, synchronization of APD-SDA and Ca-SDA patterns depends on the stabilities of both subsystems, their coupling strengths, and the spatial scales of the initial Ca-SDA patterns. Spontaneous (initial condition-independent) synchronization is promoted by enhancing APD instability and reducing Ca instability as well as stronger Ca-to-APD and APD-to-Ca coupling, a pattern formation caused by dynamical instabilities. When Ca is more unstable and APD is less unstable or APD-to-Ca coupling is weak, synchronization of APD-SDA and Ca-SDA patterns is promoted by larger initially synchronized Ca-SDA clusters, i.e., initial condition-dependent synchronization. The synchronized APD-SDA and Ca-SDA patterns can be locked in-phase, antiphase, or quasiperiodic depending on the coupling relationship between APD and Ca. These theoretical and simulation results provide mechanistic insights into the APD-SDA and Ca-SDA dynamics observed in experimental studies.

Application and effect evaluation of multidisciplinary team management model: On central venous access device associated skin impairment based on Delphi method.

OBJECTIVE: To establish a multidisciplinary management model based on Delphi method to guide nursing practice and reduce the incidence of CVAD-associated Skin Impairment (CASI) in tumor patients. METHODS: On the basis of literature review and focus group interview, the initial item pool of CASI management model for cancer patients was determined. The Delphi method was used to conduct two rounds of letter consultation with 36 authoritative and representative experts to determine the content and weight of indicators of CASI multidisciplinary management model for cancer patients. RESULTS: Most of the research group were experts with bachelor degree or above. More than 90% of experts have worked for more than 10 years; Areas of expertise include oncology care, venous therapy, wound stomatology, and dermatology. The recovery rate of the two rounds of expert correspondence questionnaire was 100%. The authority coefficient of experts was 0.898, indicating a good degree of authority. Kendall's harmony coefficients were 0.193 and 0.250, with statistically significant differences (p < 0.001). After two rounds of expert letter consultation, a multidisciplinary management model of CASI for cancer patients was initially formed, which included 15 first-level prevention indexes and 38 second-level prevention indexes of CASI for cancer patients. There were 9 first-level indexes and 16 second-level indexes of CASI treatment in tumor patients. CONCLUSION: Cancer patients based on Delphi method to construct CASI multidisciplinary management model has high reliability and scientificity, multidisciplinary management model in the management of patients with tumor CASI exploration will provide new methods for central venous catheter nursing and the new way of thinking, will also be intravenous fluids will provide a scientific basis for professional development and quality improvement and practical experience.

Development of a derivatization RP-HPLC method for determination of sulfuryl chloride in chlorosulfonic acid for gefapixant citrate manufacture.

Control of process impurities during manufacturing of drug substance is critical to ensure quality and process robustness. During commercial process development for the gefapixant citrate drug substance, several process impurities were found to derive from sulfuryl chloride, an impurity in the raw material, chlorosulfonic acid (CSA). This made controlling the CSA quality essential for commercial production of this drug substance. Various direct analysis methods were evaluated and found unsuitable because of the highly reactive nature and structural similarity of sulfuryl chloride and CSA. Therefore, a robust derivatization reversed-phase high performance liquid chromatography (RP-HPLC) method was developed and validated to accurately quantify sulfuryl chloride in CSA. The derivatization method was utilized to evaluate many CSA batches from different commercial suppliers and to establish a correlation between sulfuryl chloride levels in CSA and the levels of process impurities in downstream materials. The methodology described herein informed the development of setting the specification on sulfuryl chloride for CSA to ensure a robust process for manufacturing high-quality gefapixant citrate drug substance. The derivatization method was successfully validated and transferred to the commercial commodity supplier for release testing of CSA as a raw material for gefapixant citrate commercial campaigns.

Identification of the Immune Cell Infiltration Landscape in Head and Neck Squamous Cell Carcinoma (HNSC) for the Exploration of Immunotherapy and Prognosis.

It is generally believed that the majority of head and neck cancers develop in the mucosal epithelial cells of the mouth, pharynx, and larynx, which is collectively known as head and neck squamous cell carcinoma (HNSC). As a complex pathological process, HNSC develops through a variety of cellular and molecular events. Cancerous cells and immune cells infiltrating tumors are the main components of the tumor microenvironment. However, infiltration of HNSCs by the immune system has not been determined to date. In this work, we proposed computational algorithms to identify different immune subtypes. An analysis of the Cancer Genome Atlas (TCGA) database revealed gene expression profiles and corresponding clinical information. In HNSC patients, two immune-related genes (ZAP70 and IGKV2D-40) may be targets for immunotherapy, and these genes appear to be closely related to the prognosis. Several immunological subtypes were associated with immune function, immune checkpoints, and prognostic factors in HNSCs. Furthermore, ZAP70 is closely related to the overall survival (OS), progress-free interval (PFI), and disease-specific survival (DSS) of HNSC patients. The potential pathways that are associated with ZAP70 were found to have included adaptive immune response, response to oxidative stress, DNA replication, and lipid binding. This study provides a theoretical foundation for developing immunotherapy drugs for HNSC patients. By evaluating larger cohorts, we can gain a deeper understanding of immunotherapy and provide direction for current research on immunotherapy strategies in HNSCs.

Enhancement of Spin-Charge Conversion in Dilute Magnetic Alloys by Kondo Screening.

We derive a kinetic theory capable of dealing both with large spin-orbit coupling and Kondo screening in dilute magnetic alloys. We obtain the collision integral nonperturbatively and uncover a contribution proportional to the momentum derivative of the impurity scattering S matrix. The latter yields an important correction to the spin diffusion and spin-charge conversion coefficients, and fully captures the so-called side-jump process without resorting to the Born approximation (which fails for resonant scattering), or to otherwise heuristic derivations. We apply our kinetic theory to a quantum impurity model with strong spin-orbit, which captures the most important features of Kondo-screened Cerium impurities in alloys such as Ce_{x}La_{1-x}Cu_{6}. We find (1) a large zero-temperature spin-Hall conductivity that depends solely on the Fermi wave number and (2) a transverse spin diffusion mechanism that modifies the standard Fick's diffusion law. Our predictions can be readily verified by standard spin-transport measurements in metal alloys with Kondo impurities.

Duhaldea pterocaula (Franch.) Anderb. Attenuates Nociception and Inflammation via GABAA Receptors.

Duhaldea pterocaula (Franch.) Anderb, also known as Inula pterocaula Franch (I. pterocaula), is a folk medicine of the Yi nationality in China. The Inula plants display various biological activities, including anti-nociceptive and anti-inflammatory properties. I. pterocaula has been traditionally used for the treatment of bronchitis, vasculitis, and dizziness. However, very few studies have been reported on the pharmacology of I. pterocaula. The present study aims to characterize the anti-nociceptive and anti-inflammatory properties of I. pterocaula and explore the underlying mechanism. I. pterocaula was extracted by 95% ethanol and further portioned with petroleum ether, ethyl acetate (EA) and n-butanol, sequentially, to obtain corresponding factions with different polarities. The EA fraction (IPEA) was found to be one of the most effective fractions. It demonstrated potent analgesic effects in both acute and inflammatory pain mouse models, and caused no anti-nociceptive tolerance. Furthermore, IPEA improved the tolerance of mice to morphine. IPEA also showed potent anti-inflammatory effects on LPS-induced septic mice. BIC, a GABAAR antagonist, reversed the effects of IPEA in pain and inflammation models. Collectively, GABAARs play a key role in the pharmacological effects of IPEA. I. pterocaula may be useful as a complementary or alternative therapeutic agent for the treatment of pain and inflammation.

Scattering of Magnons at Graphene Quantum-Hall-Magnet Junctions.

Motivated by recent nonlocal transport studies of quantum-Hall-magnet (QHM) states formed in monolayer graphene's N=0 Landau level, we study the scattering of QHM magnons by gate-controlled junctions between states with different integer filling factors ν. For the ν=1|-1|1 geometry we find that magnons are weakly scattered by electric potential variation in the junction region, and that the scattering is chiral when the junction lacks a mirror symmetry. For the ν=1|0|1 geometry, we find that kinematic constraints completely block magnon transmission if the incident angle exceeds a critical value. Our results explain the suppressed nonlocal-voltage signals observed in the ν=1|0|1 case. We use our theory to propose that valley waves generated at ν=-1|1 junctions and magnons can be used in combination to probe the spin or valley flavor structure of QHM states at integer and fractional filling factors.

Current-Driven Magnetization Reversal in Orbital Chern Insulators.

Graphene multilayers with flat moiré minibands can exhibit the quantized anomalous Hall effect due to the combined influence of spontaneous valley polarization and topologically nontrivial valley-projected bands. The sign of the Hall effect in these Chern insulators can be reversed either by applying an external magnetic field, or by driving a transport current through the system. We propose a current-driven mechanism whereby reversal occurs along lines in the (current I, magnetic-field B) control parameter space with slope dI/dB=(e/h)MA_{M}(1-γ^{2})/γ, where M is the magnetization, A_{M} is the moiré unit cell area, and γ<1 is the ratio of the chemical potential difference between valleys along a domain wall to the electrical bias eV.

Activation of AMP-activated protein kinase signaling pathway ameliorates steatosis in laying hen hepatocytes.

The fatty liver hemorrhage syndrome in laying hens is a disease of lipid metabolism disorders. Importantly, energy sensor AMP-activated protein kinase (AMPK) plays an essential role in homeostasis regulation of liver lipid. The current research aims to investigate the relationship between AMPK signaling pathway and lipid metabolism in laying hen hepatocytes and explore the underlying mechanisms. The steatotic hepatocytes model of laying hen was established and treated with AMPK agonist AICAR and inhibitor compound C. The results showed that the levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol significantly declined while high-density lipoprotein cholesterol level increased in the AICAR-treated steatosis group compared with the steatosis group. Furthermore, the mRNA levels of liver kinase B1 and AMP-activated protein kinase α1 declined significantly in the steatosis group compared with those in the normal group. However, AMPK activation significantly upregulated the mRNA levels of peroxisome proliferator-activated receptor α and carnitine palmitoyl transferase-1 while downregulated the mRNA levels of acetyl CoA carboxylase, fatty acid synthase, 3-hydroxy-3-methyl glutaryl coenzyme A reductase, Sn-glycerol-3-phosphate acyltransferase, and hepatocyte nuclear factor 4α. These results suggest that activated AMPK signaling pathway increases fatty acid oxidation and reduces lipid synthesis in laying hen hepatocytes, thereby ameliorating liver steatosis.