Emerging role of N6-methyladenosine in the homeostasis of glucose metabolism.

N6-methyladenosine (m6A) is the most prevalent post-transcriptional internal RNA modification, which is involved in the regulation of diverse physiological processes. Dynamic and reversible m6A modification has been shown to regulate glucose metabolism, and dysregulation of m6A modification contributes to glucose metabolic disorders in multiple organs and tissues including the pancreas, liver, adipose tissue, skeletal muscle, kidney, blood vessels, and so forth. In this review, the role and molecular mechanism of m6A modification in the regulation of glucose metabolism were summarized, the potential therapeutic strategies that improve glucose metabolism by targeting m6A modifiers were outlined, and feasible directions of future research in this field were discussed as well, providing clues for translational research on combating metabolic diseases based on m6A modification in the future.

Investigation Driven by Network Pharmacology on Potential Components and Mechanism of DGS, a Natural Vasoprotective Combination, for the Phytotherapy of Coronary Artery Disease.

Phytotherapy offers obvious advantages in the intervention of Coronary Artery Disease (CAD), but it is difficult to clarify the working mechanisms of the medicinal materials it uses. DGS is a natural vasoprotective combination that was screened out in our previous research, yet its potential components and mechanisms are unknown. Therefore, in this study, HPLC-MS and network pharmacology were employed to identify the active components and key signaling pathways of DGS. Transgenic zebrafish and HUVECs cell assays were used to evaluate the effectiveness of DGS. A total of 37 potentially active compounds were identified that interacted with 112 potential targets of CAD. Furthermore, PI3K-Akt, MAPK, relaxin, VEGF, and other signal pathways were determined to be the most promising DGS-mediated pathways. NO kit, ELISA, and Western blot results showed that DGS significantly promoted NO and VEGFA secretion via the upregulation of VEGFR2 expression and the phosphorylation of Akt, Erk1/2, and eNOS to cause angiogenesis and vasodilation. The result of dynamics molecular docking indicated that Salvianolic acid C may be a key active component of DGS in the treatment of CAD. In conclusion, this study has shed light on the network molecular mechanism of DGS for the intervention of CAD using a network pharmacology-driven strategy for the first time to aid in the intervention of CAD.

Bioinformatics analysis of gene and microRNA targets for fibromyalgia.

OBJECTIVES: Fibromyalgia (FM) is the most common chronic pain disease in middle-aged women. Patients may also complain of migraine, irritable bowel syndrome and depression, which seriously affect their work and life, causing huge economic losses to society. However, the pathogenesis of FM is still controversial and the effect of the current treatment is far from satisfactory. METHODS: Differentially expressed genes (DEGs) and miRNAs (DEMs) were found between FM and normal blood samples. The pathway and process enrichment analysis of the genes were performed. Protein-protein interaction network were constructed. Hub genes were found and analysed in The Comparative Toxicogenomics Database. RESULTS: A total of 102 genes were up-regulated and 46 down-regulated, 206 miRNAs down-regulated, and 15 up-regulated in FM. CD38, GATM, HDC, FOS were found as canditate genes. These genes were significantly associated with musculoskeletal disease, mental disorder, immune system disease. There was partial overlap between metformin therapy-related genes and FM-related genes. CONCLUSIONS: We found DEGs and DEMs in FM patients through bioinformatics analysis, which may be involved in the occurrence and development of FM and serve as potential targets for diagnosis and treatment.

Surface Energy Driven Liquid-Drop-Like Pseudoelastic Behaviors and In Situ Atomistic Mechanisms of Small-Sized Face-Centered-Cubic Metals.

The elastic strain of conventional metals is usually below ∼1%. As the metals' sizes decrease to approximate a few nanometers, their elastic strains can approach ∼8%, and they usually exhibit pseudoelastic strain that can be as large as ∼35%. Previous studies suggested that the pseudoelastic behaviors of nanocrystals were attributed to distinctive mechanisms, including the release of stored elastic energies, the temperature-enhanced surface diffusion, etc. However, the atomistic mechanisms remain elusive. In this study, through large numbers of in situ atomic-scale tensile-fracture experiments, we report liquid-drop-like pseudoelastic behaviors of face-centered-cubic fractured single-crystalline nanowires with diameters varying from 0.5 to 2.2 nm. The ultralarge liquid-drop-like pseudoelastic strain ranged from 31.4% to 81.0% after the nanowire fracture was observed. The in situ atomic-scale investigations revealed that the atomistic mechanisms resulted from surface energy driven plastic deformation including surface diffusion mixed with shear plastic deformation as well as the release of true elastic energy. As the nanowires' diameters decrease below a critical value, the surface pressure can approach the ideal strength of metals. This ultralarge surface pressure drives atoms to diffuse mixed with dislocation nucleation/propagation, which ultimately leads to the fractured nanowires exhibiting liquid-drop-like pseudoelastic phenomena.

Plastic Deformation through Dislocation Saturation in Ultrasmall Pt Nanocrystals and Its in Situ Atomistic Mechanisms.

The atomic-scale deformation dynamic behaviors of Pt nanocrystals with size of ∼18 nm were in situ investigated using our homemade device in a high-resolution transmission electron microscope. It was discovered that the plastic deformation of the nanosized single crystalline Pt commenced with dislocation "appreciation" first, then followed by a dislocation "saturation" phenomenon. The magnitude of strain plays a key role on dislocation behaviors. At the early to medium stage of deformation, the plastic deformation was controlled by the full dislocation activities accompanied by the formation of Lomer dislocation locks from reaction of full dislocations. When the strain increased to a significant level, stacking faults and extended dislocations as well as Lomer-Cottrell locks appeared. The Lomer-Cottrell locks can unlock through transferring into Lomer dislocation locks first, and then Lomer dislocation locks were destructed under high stresses. The very high density dislocations and the frequent dislocation reactions through Lomer dislocations and Lomer-Cottrell locks may lead to work hardening in nanosized Pt.

Flagellar-dependent motility in Mesorhizobium tianshanense is involved in the early stage of plant host interaction: study of an flgE mutant.

Bacterial motility is most likely a critical factor for rhizobium to chemotactically colonize on the root surface prior to infecting leguminous plant hosts. Several studies of the rhizobium flagellar filament have been reported, but little is known about the rhizobium flagellum hook. To investigate the roles of the hook protein in flagellum synthesis in Mesorhizobium tianshanense, the hook protein-encoding gene flgE of M. tianshanense was amplified by PCR and sequenced. Comparison of the deduced amino acid sequences revealed pronounced similarities in Domain 1 and lower similarities in Domain 2, which are supposed to be related to hook structure assembly and antigenic diversity, respectively. The level of transcription of flgE increased along with the cell growth and reached its maximum at the middle log phase. Disruption of the flgE gene caused a flagellar-less phenotype, thereby causing complete loss of swimming ability, modified nutrient-related swarming ability and biofilm formation. Moreover, the absence of flagellar caused decreased bacterial attachment on the root hair, suggesting that flagellar is involved in the early stage of symbiosis process.

Brain Pathology in COVID-19: Clinical Manifestations and Potential Mechanisms.

Neurological manifestations of coronavirus disease 2019 (COVID-19) are less noticeable than the respiratory symptoms, but they may be associated with disability and mortality in COVID-19. Even though Omicron caused less severe disease than Delta, the incidence of neurological manifestations is similar. More than 30% of patients experienced "brain fog", delirium, stroke, and cognitive impairment, and over half of these patients presented abnormal neuroimaging outcomes. In this review, we summarize current advances in the clinical findings of neurological manifestations in COVID-19 patients and compare them with those in patients with influenza infection. We also illustrate the structure and cellular invasion mechanisms of SARS-CoV-2 and describe the pathway for central SARS-CoV-2 invasion. In addition, we discuss direct damage and other pathological conditions caused by SARS-CoV-2, such as an aberrant interferon response, cytokine storm, lymphopenia, and hypercoagulation, to provide treatment ideas. This review may offer new insights into preventing or treating brain damage in COVID-19.

DNA repair gene XRCC4 codon 247 polymorphism modified diffusely infiltrating astrocytoma risk and prognosis.

The DNA repair gene X-ray cross-complementary group 4 (XRCC4), an important caretaker of the overall genome stability, is thought to play a major role in human tumorigenesis. We investigated the association between an important polymorphic variant of this gene at codon 247 (rs373409) and diffusely infiltrating astrocytoma (DIA) risk and prognosis. This hospital-based case-control study investigated this association in the Guangxi population. In total, 242 cases with DIA and 358 age-, sex-, and race-matched healthy controls were genotyped using TaqMan-PCR technique. We found a significant difference in the frequency of XRCC4 genotypes between cases and controls. Compared with the homozygote of XRCC4 codon 247 Ala alleles (XRCC4-AA), the genotypes of XRCC4 codon 247 Ser alleles (namely XRCC4-AS or -SS) increased DIA risk (odds ratios [OR], 1.82 and 2.89, respectively). Furthermore, XRCC4 polymorphism was correlated with tumor dedifferentiation of DIA (r = 0.261, p < 0.01). Additionally, this polymorphism modified the overall survival of DIA patients (the median survival times were 26, 14, and 8 months for patients with XRCC4-AA, -AS, and -SS, respectively). Like tumor grade, XRCC4 codon 247 polymorphism was an independent prognostic factor influencing the survival of DIA. These results suggest that XRCC4 codon 247 polymorphism may be associated with DIA risk and prognosis among the Guangxi population.

Effectiveness of sleep interventions to reduce delirium in critically ill patients: A systematic review and meta-analysis.

PURPOSE: To analyze the effectiveness of sleep interventions in reducing the incidence and duration of delirium in the ICU. MATERIALS AND METHODS: We searched the PubMed, Embase, CINAHL, Web of Science, Scopus, and Cochrane databases for relevant randomized controlled trials from inception to August 2022. Literature screening, data extraction, and quality assessment were performed independently by two investigators. Data from the included studies were analyzed using Stata and TSA software. RESULTS: Fifteen randomized controlled trials were eligible. Meta-analysis showed that the sleep intervention was associated with a reduced incidence of delirium in the ICU (RR = 0.73, 95% CI = 0.58 to 0.93, p < 0.001) compared to the control group. The results of the trial sequence analysis further confirm that sleep interventions are effective in reducing the occurrence of delirium. Pooled data from the three dexmedetomidine trials showed significant differences in the incidence of ICU delirium between groups (RR = 0.43, 95% CI = 0.32 to 0.59, p < 0.001). The respective pooled results of other sleep interventions (e.g., light therapy, earplugs, melatonin, and multicomponent nonpharmacologic treatments) did not find a significant effect on reducing the incidence and duration of ICU delirium (p > 0.05). CONCLUSIONS: The current evidence suggests that non-pharmacological sleep interventions are not effective in preventing delirium in ICU patients. However, limited by the number and quality of included studies, future well-designed multicenter randomized controlled trials are still needed to validate the results of this study.

Erratum: Upper limit of the transition temperature of superconducting materials.

[This corrects the article DOI: 10.1016/j.patter.2022.100609.].

A nonuniform demagnetizing field model for both static and dynamic responses of anisotropic magnetoresistive thin film sensors.

In this paper, an anisotropic magnetoresistive (AMR) thin film sensor which can be used for magnetic scale has been prepared, and its output voltage is about 4.7-4.9 mV V-1. On the basis of the Stoner-Wohlfarth model and with considering the non-uniformity of the demagnetizing field along the width direction of the strips, both the static and dynamic responses of the AMR sensors have been calculated. The results have shown that the calculated results are in agreement with the experimental data. The magnetization rotation in the magnetic sensor strongly depends on the nonuniform demagnetizing field along the width direction. The magnetization at the center is easily rotated into the field direction, and the magnetization at the edge is difficult to be rotated. The smaller the width of the magnetoresistive strip is, the larger both the demagnetizing field at the edge and the saturation field of the magnetic sensor are. The results are helpful for understanding the magnetization rotation of magnetic sensors and developing the magnetic sensors with high performance.

Chemical inhomogeneity-induced profuse nanotwinning and phase transformation in AuCu nanowires.

Nanosized metals usually exhibit ultrahigh strength but suffer from low homogeneous plasticity. The origin of a strength-ductility trade-off has been well studied for pure metals, but not for random solid solution (RSS) alloys. How RSS alloys accommodate plasticity and whether they can achieve synergy between high strength and superplasticity has remained unresolved. Here, we show that face-centered cubic (FCC) RSS AuCu alloy nanowires (NWs) exhibit superplasticity of ~260% and ultrahigh strength of ~6 GPa, overcoming the trade-off between strength and ductility. These excellent properties originate from profuse hexagonal close-packed (HCP) phase generation (2H and 4H phases), recurrence of reversible FCC-HCP phase transition, and zigzag-like nanotwin generation, which has rarely been reported before. Such a mechanism stems from the inherent chemical inhomogeneity, which leads to widely distributed and overlapping energy barriers for the concurrent activation of multiple plasticity mechanisms. This naturally implies a similar deformation behavior for other highly concentrated solid-solution alloys with multiple principal elements, such as high/medium-entropy alloys. Our findings shed light on the effect of chemical inhomogeneity on the plastic deformation mechanism of solid-solution alloys.

Evaluating the ecological vulnerability of Chongqing using deep learning.

This study used deep learning to evaluate the ecological vulnerability of Chongqing, China, discuss the deep learning evaluations of ecological vulnerability, and generate vulnerability maps that support local ecological environment protection and governance decisions and provide reference for future studies. The information gain ratio was used to screen the influencing factors, selecting 16 factors that influence ecological vulnerability. Deep neural network (DNN) and convolutional neural network (CNN) methods were used for modeling, and two ecological vulnerability maps of the study area were generated. The results showed that the mean absolute error and root mean square error of the DNN and CNN models were relatively small, and the fitting accuracy was high. The area under the receiver operating characteristic curve of the CNN model was 0.926, which was better than that of the DNN model (0.888). Random forest was applied to calculate the importance of the influencing factors in the two models. Because the main factor was geological features, the relative ecological vulnerability was mainly affected by karst topography. Through the analysis of the ecological vulnerability map, the areas with higher vulnerability are the karst mountains of Dabashan, Wushan, and Qiyaoshan in the northeast and southeast, as well as the valley between mountains and cities in the center and west of the study area. According to the investigation of these areas, the primary ecological problems are low forest quality, structural irregularities caused by self-geological factors, severe desertification, and soil erosion. Human activity is also an important factor that causes ecological vulnerability in the study area. In conclusion, deep learning, particularly CNN models, can be used for ecological vulnerability assessments. The ecological vulnerability maps conformed to the basic cognition of field surveys and can provide references for other deep learning vulnerability studies. While the overall vulnerability of the study area is not high, ecological problems that lead to its vulnerability should be addressed by future ecological protection and management measures.

High-throughput novel microsatellite marker of faba bean via next generation sequencing.

BACKGROUND: Faba bean (Vicia faba L.) is an important food legume crop, grown for human consumption globally including in China, Turkey, Egypt and Ethiopia. Although genetic gain has been made through conventional selection and breeding efforts, this could be substantially improved through the application of molecular methods. For this, a set of reliable molecular markers representative of the entire genome is required. RESULTS: A library with 125,559 putative SSR sequences was constructed and characterized for repeat type and length from a mixed genome of 247 spring and winter sown faba bean genotypes using 454 sequencing. A suit of 28,503 primer pair sequences were designed and 150 were randomly selected for validation. Of these, 94 produced reproducible amplicons that were polymorphic among 32 faba bean genotypes selected from diverse geographical locations. The number of alleles per locus ranged from 2 to 8, the expected heterozygocities ranged from 0.0000 to 1.0000, and the observed heterozygosities ranged from 0.0908 to 0.8410. The validation by UPGMA cluster analysis of 32 genotypes based on Nei's genetic distance, showed high quality and effectiveness of those novel SSR markers developed via next generation sequencing technology. CONCLUSIONS: Large scale SSR marker development was successfully achieved using next generation sequencing of the V. faba genome. These novel markers are valuable for constructing genetic linkage maps, future QTL mapping, and marker-assisted trait selection in faba bean breeding efforts.

Horizontal Oxidation Diffusion Behavior of MEMS-Based Tungsten-Rhenium Thin Film Thermocouples.

Tungsten-rhenium thin film thermocouples (TFTCs) are well suited for the surface temperature monitoring of hot components due to their small size, rapid response and low cost. In this study, a tungsten-rhenium TFTC with SiC protective film on all parts except the pads was fabricated by a microelectromechanical system (MEMS) process. During the low to medium temperature (-40 °C to 500 °C) repeatability test phase, the thermal voltage from the TFTC agreed well with that of the standard tungsten-rhenium thermocouple. However, during the high temperature test phase, the TFTC lost electronic response at around 620 °C. Failure analysis of the TFTC tested at 620 °C was performed by microscopy, scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), laser scanning confocal microscope (LSCM) and statistics. The results showed that the pads were oxidized without the protective layer, the number of oxidized protrusions distributed in this TFTC from the pad to the node decreases more and more slowly and the size of the oxidized protrusions also becomes smaller and smaller. This demonstrates the presence of horizontal oxidation diffusion in TFTCs, further illustrating the importance of pad protection and provides a direction for the subsequent structural optimization and the extension of the service life of TFTCs and other sensors.

Effect of Annealing Time on the Cyclic Characteristics of Ceramic Oxide Thin Film Thermocouples.

Oxide thin film thermocouples (TFTCs) are widely used in high-temperature environment measurements and have the advantages of good stability and high thermoelectric voltage. However, different annealing processes affect the performance of TFTCs. This paper studied the impact of different annealing times on the cyclic characteristics of ceramic oxide thin film thermocouples. ITO/In2O3 TFTCs were prepared on alumina ceramics by a screen printing method, and the samples were annealed at different times. The microstructure of the ITO film was studied by scanning electron microscopy (SEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The results show that when the annealing temperature is fixed, the stability of the thermocouple is worst when it is annealed for 2 h. Extending the annealing time can improve the properties of the film, increase the density, slow down oxidation, and enhance the thermal stability of the thermocouple. The thermal cycle test results show that the sample can reach five temperature rise and fall cycles, more than 50 h, and can meet the needs of stable measurement in high temperature and harsh environments.

Upper limit of the transition temperature of superconducting materials.

Why are the transition temperatures (T c) of superconducting materials so different? The answer to this question is not only of great significance in revealing the mechanism of high-T c superconductivity but also can be used as a guide for the design of new superconductors. However, so far, it is still challenging to identify the governing factors affecting the T c. In this work, with the aid of machine learning and first-principles calculations, we found a close relevance between the upper limit of the T c and the energy-level distribution of valence electrons. It implies that some additional inter-orbital electron-electron interaction should be considered in the interpretation of high-T c superconductivity.

Tracking the sliding of grain boundaries at the atomic scale.

Grain boundaries (GBs) play an important role in the mechanical behavior of polycrystalline materials. Despite decades of investigation, the atomic-scale dynamic processes of GB deformation remain elusive, particularly for the GBs in polycrystals, which are commonly of the asymmetric and general type. We conducted an in situ atomic-resolution study to reveal how sliding-dominant deformation is accomplished at general tilt GBs in platinum bicrystals. We observed either direct atomic-scale sliding along the GB or sliding with atom transfer across the boundary plane. The latter sliding process was mediated by movements of disconnections that enabled the transport of GB atoms, leading to a previously unrecognized mode of coupled GB sliding and atomic plane transfer. These results enable an atomic-scale understanding of how general GBs slide in polycrystalline materials.

Erector spinae plane block at lower thoracic level for analgesia in lumbar spine surgery: A randomized controlled trial.

BACKGROUND: Patients undergoing lumbar spine surgery usually suffer severe pain in the postoperative period. The erector spinae plane block (ESPB), first published in 2016, can anesthetize the ventral and dorsal rami of thoracic nerves and produce an extensive multi-dermatomal sensory block. AIM: To assess whether bilateral ultrasound-guided ESPB at a lower thoracic level could improve pain control and quality of recovery in patients undergoing lumbar spine surgery. METHODS: A total of 60 patients aged 18-80 years scheduled to undergo lumbar spine surgery with general anesthesia were randomly assigned to two groups: ESPB group (preoperative bilateral ultrasound-guided ESPB at T10 vertebral level) and control group (no preoperative ESPB). Both groups received standard general anesthesia. The main indicator was the duration to the first patient controlled intravenous analgesia (PCIA) bolus. RESULTS: In the ESPB group, the duration to the first PCIA bolus was significantly longer than that in the control group (h) [8.0 (4.5, 17.0) vs 1.0 (0.5, 6), P < 0.01], and resting and coughing numerical rating scale (NRS) scores at 48 h post operation were significantly lower than those in the control group (P < 0.05). There was no significant difference between the two groups regarding resting and coughing NRS scores at 24 h post operation. Sufentanil consumption during the operation was significantly lower in the ESPB group than in the control group (P < 0.01), while there was no significant difference between the two groups regarding morphine consumption at 24 or 48 h post operation. In the ESPB group, Modified Observer's Assessment of Alertness/Sedation score within 20 min after extubation was higher and duration in the post-anesthesia care unit was shorter than those in the control group (P < 0.01). CONCLUSION: In patients undergoing lumbar spine surgery, ultrasound-guided ESPB at a lower thoracic level improves the analgesic effect, reduces opioid consumption, and improves postoperative recovery.

Enhanced negative magnetoresistance near the charge neutral point in Cr doped topological insulator.

Negative magnetoresistance (MR) is not only of great fundamental interest for condensed matter physics and materials science, but also important for practical applications, especially magnetic data storage and sensors. However, the microscopic origin of negative MR is still elusive and the nature of the negative MR in magnetic topological insulators has still not been completely elucidated. Here, we report magnetotransport studies on Cr doped (Bi1-x Sb x )2Te3 topological insulator thin films grown by magnetron sputtering. At the temperature of 2 K, a giant negative MR reaching 61% is observed at H = 2 T. We show that the negative MR is closely related to the position of the Fermi level, and it reaches the maximum when the Fermi level is gated near the charge neutral point. We attribute these results to the Coulomb potential due to the random composition fluctuations in Cr doped (Bi1-x Sb x )2Te3. Our results provide a deeper insight into the mechanism of negative MR, and are helpful to realize the quantum anomalous Hall effect in the sputtered Cr-(Bi1-x Sb x )2Te3 thin-film systems by tuning the Fermi level and reducing disorder effects.