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Diabetes mellitus (DM) and arginine vasopressin deficiency (AVP‐D) are characterized by polyuria. Marfan syndrome is an autosomal dominant disorder caused by pathogenetic variants in FBN1. Here, we report a patient with type 2 diabetes mellitus, AVP‐D, and Marfan syndrome. Although the coexistence of type 2 diabetes mellitus and AVP‐D is rare, for those patients with type 2 diabetes mellitus, the existence of AVP‐D should be considered when polyuria is not in accordance with the blood glucose levels, especially for those with a low urine specific gravity. Specific symptoms or signs help to identify Marfan syndrome early, and genetic testing of the FBN1 pathogenetic variant helps to make a definitive diagnosis. [ABSTRACT FROM AUTHOR]

Background: the mortality associated with severe malaria due to Plasmodiun falciparum remains high despite improvements in malaria management. Case prensentation: this case series aims to describe the efficacy and safety of the exchange transfusion combined with artesunate (ET-AS) regimen in severe P. falciparum malaria. Eight patients diagnosed with severe P. falciparum malaria were included. All patients underwent ET using the COBE Spectra system. The aimed for a post-exchange hematocrit of 30%. Half the estimated blood volume was removed and replaced using fresh frozen plasma. The regimen was well-tolerated without complications. The parasite clearance time ranged from 1 ~ 5 days. Five patients with cerebral malaria exhibited full improved consciousness within 3 days, while patient2 with hemolysis improved on day 2. Liver function improved within 1 ~ 6 days, and patient 1 and patient 6 showed improvements renal function on days 18 and 19, respectively. The length of intensive care unit stay range from 2 ~ 10 days, and all patients treated with ET-AS remained in the hospital for 3 ~ 19 days. Conclusions: these preliminary results suggest that ET-AS regimens are a safe and effective therapy for severe P. falciparum malaria and can benefit patients in clinical settings. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) is one of the most abundant chemical modifications on mRNA in eukaryotes. RNA-binding proteins containing the YT521-B (YTH) domain play crucial roles in post-transcriptional regulation of plant growth, development, and stress response by reading the m6A mark. However, the YTH domain-containing RNA-binding protein family has not been studied in a valuable and medicinal tree such as Cinnamomum camphora (C. camphora) yet. In this study, we identified 10 YTH genes in C. camphora, located on eight out of 12 chromosomes. Phylogenetic analysis revealed that these genes can be classified into two major classes, YTHDF (CcDF) and YTHDC (CcDC). Closely related CcYTHs within the same class exhibited a similar distribution of conserved motifs and domain organization, suggesting functional similarities among these closely related CcYTHs. All CcYTH proteins possessed a highly conserved YTH domain, with CcDC1A containing an additional CCCH domain. The liquid–liquid phase separation (LLPS) predictions indicate that CcDC1A, CcDF1A, CcDF1C, CcDF3C, CcDF4C, and CcDF5C may undergo phase transitions. Quantitative expression analysis revealed that tissue-specific expression was observed fo CcYTHs. Notably, there were two genes, CcDF1A and CcDF5C; both exhibited significantly higher expression levels in various tissues than other genes, indicating that the m6A-YTH regulatory network in C. camphora might be quite distinct from that in most plants such as Arabidopsis thaliana (A. thaliana) with only one abundant YTH protein. According to the analysis of the up-stream cis-regulatory elements of these YTH genes, these genes could be closely related to stress, hormones, and development. The following stress response experiments further verified that their expression levels indeed changed under both PEG and NaCl treatments. These findings not only provide a foundation for future functional analysis of CcYTHs in C. camphora, but also provide insights into the functions of epigenetic mark m6A in forest trees. [ABSTRACT FROM AUTHOR]

The loss of midbrain dopaminergic (DA) neurons is the fundamental pathological feature of Parkinson's disease (PD). PD causes chronic pain in two-thirds of patients. Recent studies showed that the activation of the pedunculopontine tegmental nucleus (PPTg) can effectively relieve inflammatory pain and neuropathic pain. The PPTg is located in the pontomesencephalic tegmentum, a target of deep brain stimulation (DBS) treatment in PD, and is involved in motor control and sensory integration. To test whether the lesion of midbrain DA neurons induced pain hypersensitivity, and whether the chemogenetic activation of the PPTg could modulate the pain, the AAV-hM3Dq receptor was transfected and expressed into the PPTg neurons of 6-hydroxydopamine-lesioned mice. In this study, von Frey, open field, and adhesive tape removal tests were used to assess animals' pain sensitivity, locomotor activity, and sensorimotor function and somatosensory perception, respectively. Here, we found that the lesion of midbrain DA neurons induced a minor deficit in voluntary movement but did not affect sensorimotor function and somatosensory perception in the tape removal test. The results showed that lesion led to pain hypersensitivity, which could be alleviated both by levodopa and by the chemogenetic activation of the PPTg. Activating the PPTg may be a potential therapeutic strategy to relieve pain phenotypes in PD. [ABSTRACT FROM AUTHOR]

Although VO 2 possesses an attractive theoretical specific capacity and a shear-type structure to resist lattice shear during repeated Zn2+ insertion/extraction, its poor electrical conductivity, easy self-aggregation, and inferior stability lead to sluggish reaction kinetics and unsatisfactory Zn2+ storage performance. In this work, we successfully constructed novel 2D VO 2 nanoplates embedded in a carbon matrix (VO 2 /carbon) utilizing a straightforward hydrothermal approach without using any template or calcination procedure. The thickness of the carbon layer can be tuned by modulating the experimental conditions. Impressively, the obtained 2D VO 2 /carbon with the optimal thickness of the carbon layer displayed satisfactory cyclic stability (63 % capacity maintained after 2500 cycles at 3 A g-1), excellent rate capability (202 mAh g-1 at 5 A g-1), and high specific capacity (501 mAh g-1 at 0.1 A g-1) as cathode material for aqueous zinc ion batteries (ZIBs), attributed to the desirable 2D nanoplate structure that offers effective pathways for Zn2+ diffusion together with sufficient electroactive sites for redox reactions and moderate carbon coating that buffers the volume changes in the course of repeated insertion/extraction of Zn2+ and accelerates charge/ion transfer. Furthermore, two assembled Zn//VO 2 /carbon coin cells successfully lit an orange light-emitting diode (LED) light for over 5 h, highlighting their potential as ideal candidates for low-cost, high-performance, environmentally friendly, and intrinsically safe energy storage devices. [ABSTRACT FROM AUTHOR]

[Display omitted] Multidrug-resistant (MDR) bacteria-infected wound healing remains greatly challenging, especially in diabetic patients. Herein, a novel nano-drug delivery based on endogenous glucose-driven cascade reaction is proposed for boosting MDR bacteria-infected diabetic wound healing with high efficacy by improving wound microenvironment and enhancing photodynamic antibacterial activity. The composite nanoagent is first self-assembled by integrating berberine (B BR) and epigallocatechin gallate (E GCG) from natural plant extracts, named as BE NPs , which is successively coated with manganese dioxide nanoshells (M nO 2 NSs) and glucose oxidase (G OX) to form the final BEMG NPs. The cascade reaction is triggered by glucose at the wound site of diabetes which is specifically catalyzed by GOX in the BEMG NPs to produce gluconic acid and hydrogen peroxide (H 2 O 2). That is subsequently to decompose MnO 2 NSs in the BEMG NPs to generate oxygen (O 2). The BEMG NPs as photosensitizers effectively produce reactive oxygen species (ROS) to enhance the eradication of bacteria with the assistance of O 2. Under the synergistic function of the cascaded reaction, the BEMG NPs present excellent antibacterial efficacy even for MDR bacteria. The in vivo experiments explicitly validate that the constructed nano-drug delivery can augment the MDR bacteria-infected diabetic wound healing with excellent biosafety. The as-proposed strategy provides an instructive way to combat ever-threatening MDR bacteria, which particularly is beneficial for diabetic patients. [ABSTRACT FROM AUTHOR]

In this study, a novel NiO/Co 3 O 4 /KNbO 3 heterostructured electrocatalyst with NiO and Co 3 O 4 particles coupled on KNbO 3 cubes was constructed using simple sol–gel and calcination processes. The formation of multiple interfaces between NiO, Co 3 O 4 , and KNbO 3 in the heterostructure contributed to a synergistic effect, adjusted the electronic structure, and generated abundant active sites at the interfaces. As a result, the NiO/Co 3 O 4 /KNbO 3 electrocatalyst exhibited remarkable urea electrolysis performance, including a low potential of 1.67 V at 100 mA cm−2 and a small Tafel slope of 29 mV dec−1. Furthermore, the change in the overpotential was negligible even after a rigorous stability test of 3000 cycles, highlighting its exceptional durability and reliability. This study provides a novel structural engineering strategy for achieving efficient hydrogen production and purification from urea-containing wastewater. [ABSTRACT FROM AUTHOR]

Efforts to develop high-performance electrocatalysts for the hydrogen evolution reaction (HER) are of utmost importance in ensuring sustainable hydrogen production. The controllable fabrication of inexpensive, durable, and high-efficient HER catalysts still remains a great challenge. Herein, we introduce a universal strategy aiming to achieve rapid synthesis of highly active hydrogen evolution catalysts using a controllable hydrogen insertion method and solvothermal process. Hydrogen vanadium bronze HxV2O5 was obtained through controlling the ethanol reaction rate in the oxidization process of hydrogen peroxide. Subsequently, the intermetallic PtCoVO supported on two-dimensional graphitic carbon nitride (g-C3N4) nanosheets was prepared by a solvothermal method at the oil/water interface. In terms of HER performance, PtCoVO/g-C3N4 demonstrates superior characteristics compared to PtCo/g-C3N4 and PtCoV/g-C3N4. This superiority can be attributed to the notable influence of oxygen vacancies in HxV2O5 on the electrical properties of the catalyst. By adjusting the relative proportions of metal atoms in the PtCoVO/g-C3N4 nanomaterials, the PtCoVO/g-C3N4 nanocomposites show significant HER overpotential of η10 = 92 mV, a Tafel slope of 65.21 mV dec−1, and outstanding stability (a continuous test lasting 48 h). The nanoarchitecture of a g-C3N4-supported PtCoVO nanoalloy catalyst exhibits exceptional resistance to nanoparticle migration and corrosion, owing to the strong interaction between the metal nanoparticles and the g-C3N4 support. Pt, Co, and V simultaneous doping has been shown by Density Functional Theory (DFT) calculations to enhance the density of states (DOS) at the Fermi level. This augmentation leads to a higher charge density and a reduction in the adsorption energy of intermediates. [ABSTRACT FROM AUTHOR]

Objective: MicroRNA-related single-nucleotide polymorphisms (miR-SNPs) can alter microRNA (miRNA) expression profiles, thereby influencing the risk of rheumatic diseases. Herrin a case control study, six miR-SNPs in miRNA processing machinery genes, namely RAN (rs14035), XPO5 (rs11077), Dicer (rs3742330), GEMIN3 (rs197412), GEMIN4 (rs2740348), and TNRC6B (rs9623117), were genotyped to assess their correlation with the risk of systemic lupus erythematosus (SLE). Methods: We included 119 patients with SLE and 130 healthy controls. The genotypes of the six miR-SNPs were determined using polymerase chain reaction (PCR). Serum cytokine levels were assessed using a cytometric bead array, and fluorescent probe technology was used to determine plasma reactive oxygen species (ROS) levels. Results: The AA genotype of Dicer was correlated with a 0.566-fold decreased risk of SLE compared with that of the AG + GG genotype (odds ratio, 0.566; 95% CI, 0.342–0.935; p =.026), and the rs3742330 A allele was associated with a significantly decreased risk of SLE (p =.035) compared with that of the rs3742330G allele. Additionally, AA genotype carriers exhibited lower levels of interleukin-6 (IL-6) in the blood (p =.013). Subsequent analysis revealed increased ROS production in patients with SLE than that in the controls (621.042 ± 425.285 vs 499.966 ± 302.273, p =.011). Conclusion: Our findings suggest that ROS generation participates in SLE pathogenesis. The identification of Dicer gene SNP rs3742330 as a potential modifier of SLE risk via mediating IL-6 overproduction suggests a potential avenue for targeted interventions to manage SLE and its associated immune dysregulation. [ABSTRACT FROM AUTHOR]

With a fixed prize budget, to increase total effort, we design a two-stage lottery contest where heterogeneous agents face the prospect of promotion and the threat of demotion from one stage to the next. We develop two competing theoretical models to generate predictions about behavior: (i) the standard economic model and (ii) a behavioral model where agents derive non-monetary utility from winning. The experimental results provide strong support for the use of promotion and demotion in contests when abilities are homogeneous, however, they do not provide strong support for the use of promotion and demotion in contests when ability differences are large. Our experimental results are consistent with the predictions made by the behavioral model. [ABSTRACT FROM AUTHOR]

Changes in the habitats of species can provide insights into the impact of climate change on their habitats. Species in the genus Morina (Morinoideae) are perennial herbaceous plants that are mainly distributed in the South Asian Mountains and Eastern Mediterranean. In China, there are four species and two varieties of this genus distributed across the Yunnan, Sichuan, Qinghai, and Gansu provinces. This study used the optimal MaxEnt model to simulate past, current, and future potentially suitable habitats of Morina kokonorica and Morina chinensis. Seventy data of M. kokonorica occurrences and 3 of M. chinensis were used in the model to predict potentially suitable habitats. The model prediction results indicated that both M. kokonorica and M. chinensis exhibited trends of northward migration to higher latitudes and westward migration along the Himalayas to higher elevations, suggesting that the northern valleys of Hengduan Mountains and northern and eastern parts of the Himalayas were potential refugia for M. kokonorica, and the potential refugia for M. chinensis was located in the eastern part of Qinghai‐Tibet Plateau. The results of this niche analysis showed that the two species had higher levels of interspecific competition and that the environmental adaptability of M. chinensis was stronger. This research could help further understand the response pattern of Morina to environmental change, to understand the adaptability of species to the environment, and promote the protection of species. [ABSTRACT FROM AUTHOR]

A recent study by Liu et al. (2020) suggested that due to the saturation of equatorially trapped planetary waves with different dynamical types, temporal periods, meridional and baroclinic modes, complex layer structures of vertical velocity shear and hence turbulent mixing could frequently occur in the thermocline of the eastern equatorial Pacific. We investigated the occurrence of the interior turbulent mixing as indicated by shear instabilities, above the Equatorial Undercurrent (EUC) core at three equatorial sites along 140°W, 170°W, and 165°E, respectively, based mainly on data from the Tropical Atmosphere and Ocean (TAO) mooring array. We found that turbulent mixing bursts persisted in the thermocline of all three sites. Specifically, the interior turbulent mixing layers (ITMLs) could occur in probability of approximately 68%, 53%, and 48% at the three sites, respectively. The overall occurrence probability shows obvious and similar biannual variations at 140°W and 170°W, which is higher in boreal from late summer to winter and lower in spring. Vertically, the ITMLs are primarily located above the EUC core and prevail in deeper (shallower) layers from late summer to winter (spring). Most ITMLs (70%) lasted for hours to 3 days, and a few of them (15%) for more than 7 days. The thicknesses of ITMLs were concentrated between 15 and 55 m. At 165°E, the vertical distribution of ITML occurrence probability was different from that at 140°W and 170°W, as it did not show a preference for depths; the durations of ITMLs are short (also from hours to several days) and their thicknesses were between 5 and 25 m. These properties, particularly the high occurrence probability, and short durations demonstrated the persistence of thermocline mixing in the western to eastern equatorial Pacific thermocline and confirmed the generation mechanism by persistent equatorial waves as well. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) are commonly used in conjunction with chemotherapy to improve treatment outcomes for patients with gastric cancer. Since AFP could influence immunity by both inhibiting natural killer (NK) cells and regulating negatively the function of dendritic cells, we evaluated the influence of baseline serum alpha-fetoprotein (AFP) levels on the curative effect of ICIs in advanced gastric cancer (AGC) patients. Methods: A retrospective analysis was conducted on 158 AGC patients who underwent ICI treatment. The patients were divided into high and low groups based on the AFP threshold of 20 ng/ml. The efficacy of ICI treatment was assessed using objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: The higher levels of baseline AFP were found to be associated with a decrease in the effectiveness of ICIs, as evidenced by a DCR of 50.0% in the group with high AFP levels compared to 87.7% in the group with low AFP levels (P < 0.001). Further analysis using Kaplan-Meier survival techniques indicated that a high AFP level was linked to shorter progression-free survival (PFS) (P < 0.001) and overall survival (OS) (P = 0.001) in AGC individuals receiving ICIs. After propensity score matching, a log rank test revealed that the high AFP group had a decrease in median PFS (P = 0.011) and median OS (P = 0.036) compared to the low AFP group. The high AFP levels also showed its association with shorter PFS and OS in the subgroup analysis of ICI plus chemotherapy patients. Conclusions: Baseline AFP levels may predict immune checkpoint inhibitor treatment efficacy in AGC patients. [ABSTRACT FROM AUTHOR]

Accurate identification and understanding of various metallic minerals are crucial for deciphering geological formations, structures, and ages. Giving their pivotal role as essential natural resources, a microscopic exploration of metallic minerals becomes imperative. Traditional analytical methods, while helpful, exhibit certain limitations. However, terahertz time-domain spectroscopy, distinguished by its high signal-to-noise ratio, expansive frequency band, and low incident wave energy, is a promising complement to conventional techniques in characterizing metallic minerals. This study employs terahertz time-domain spectroscopy to examine samples of Stibnite, Sphalerite, Galena, and Pyrite originating from diverse geological conditions. The vibrations of molecules within these metallic minerals induce discernible changes in the terahertz spectra. Our findings untiate the extensive potential of terahertz time-domain spectroscopy in the characterization of metallic minerals, affirming its considerable practical value in mineral resource exploration. [ABSTRACT FROM AUTHOR]

Mission scheduling is an effective method to increase the value of satellite missions and can greatly improve satellite resource management and quality of service. Based on the priority-based task scheduling model, this paper proposes a CubeSat scheduling method that takes operational reliability into account, considering the impact of scheduling results on reliable operation. In this method, the available energy and the time window are used as scheduling resources, and the average state of charge of the lithium battery and the number of task start-ups are defined as two indices to measure its reliability. To meet the mission requirements and energy availability of photovoltaic (PV) solar panel and battery constraints, the scheduling model is constructed with an objective function that includes mission priority and reliability index. The branch and bound (BB) method and analytical hierarchy process (AHP) method are used to solve the scheduling problem. The example analysis compares different scheduling results and verifies the effectiveness of the proposed scheduling method. Compared with the existing methods, it comprehensively considers the mission value and operational reliability of the CubeSat, improves the energy reserve level of the CubeSat, and reduces the surge current caused by the start-up of tasks. [ABSTRACT FROM AUTHOR]

This study aims to explore the roles of multiple gust fronts (i.e., outflow boundaries) during a short-lived extreme rainfall that occurred in the Greater Bay Area of South China in the afternoon of 1 August 2021. Through the use of microbarographs and Doppler weather radars, the research highlights how the interactions of five gust fronts, approaching the region from different directions, have contributed to the high precipitation efficiency and damaging surface winds during the event. The close convergence of these gust fronts funneled unstable air masses into the region of interest, priming the mesoscale convective environment. Some isolated convection initiated before the gust fronts' arrival. Preceding the arrival of these gust fronts, subtle wave-like pressure jumps were identified from the high-frequency (1 Hz) microbarograph observations. The amplitude of the pressure jump is approximately 40 Pa with minimal changes in air temperature. During the early stage of the gust front passages, very high-frequency oscillations in surface pressure are recognized, indicating interaction between the density currents and the low-level troposphere. As suggested through numerical simulations, the subtle pressure jumps are associated with upward displacements of isentropic surfaces aloft, deepening the moist layer and enhancing the lapse rate that are conducive to convective development. The simulated vertical profiles show no evident capping inversion above the dry neutral boundary layer, suggesting that the pressure jumps are likely to be dynamically induced through the collision of the outflows and environmental air masses. The findings of this study suggest the potential application of microbarographs in the nowcasting of the convective development associated with gust fronts. [ABSTRACT FROM AUTHOR]

The global expansion of online language courses is on the rise, offering greater flexibility in the approaches to learning design. This study delves into the exploration of the fundamental learning design patterns within a K-12 synchronous language course. Leveraging a rich array of textual data, including syllabi, textbooks, course outlines, student behavior data, and recorded online instructional videos, network analysis and discourse analysis were employed. Results spotlighted the pivotal role of “dialogue” in connecting various learning activities. Furthermore, the study underscores the significance of language usage over strict adherence to grammatical rules and phonetic pronunciation. Additionally, technology has transcended its conventional role as a mere tool for reinforcing teacher authority, but it has evolved into an environment where instructors regain face-to-face authority, thereby influencing semi-recursive interactions among learners throughout the course. These findings highlight the importance of dialogue and language use in online language instruction, as well as emphasize the transformative potential of technology in reshaping teacher-student interactions. [ABSTRACT FROM AUTHOR]

Objective. To investigate the relationship between glucagon-like peptide-1 receptor gene polymorphisms and susceptibility to early onset type 2 diabetes. Methods. Samples from 316 type 2 diabetes patients with early onset type 2 diabetes (n = 137) and late-onset type 2 diabetes (n = 179) and 145 nondiabetic individuals were analyzed. Multiplex PCR combined with resequencing Hi-Reseq technology was used to detect single nucleotide polymorphisms of the glucagon-like peptide-1 receptor gene, and the allele frequency, genotype distribution, and clinical parameters were analyzed between each diabetes subgroup and the control group. Results. Sixteen single nucleotide polymorphisms were identified in the exonic region of the glucagon-like peptide-1 receptor gene according to the minor allele frequency (MAF > 0.05) in the participants. Among these, the glucagon-like peptide-1 receptor rs3765467 (G⟶A) mutation was statistically associated with early onset type 2 diabetes. Compared with that of the GG carriers, carriers of genotype AA at rs3765467 had a decreased risk of early onset type 2 diabetes after adjusting for sex and body mass index. In the dominant model, the frequencies of the rs3765467 AA + GA genotype were significantly decreased in the early onset type 2 diabetes group, and carriers of genotype AA + GA at rs3765467 had a decreased risk of early onset type 2 diabetes after adjusting for sex and body mass index. Moreover, fasting C peptide levels were significantly higher in GA + AA genotype carriers than those in GG genotype carriers. Conclusion. The glucagon-like peptide 1 receptor rs3765467 polymorphism was significantly associated with age at type 2 diabetes diagnosis and thus may be used as a marker to screen and detect individuals at risk of developing early onset type 2 diabetes. [ABSTRACT FROM AUTHOR]

Heart failure (HF) and permanent atrial fibrillation (AF) interact mutually, exacerbating hemodynamic effects and causing adverse outcomes and increased healthcare costs. Monitoring hemodynamic indicators in patients with these comorbidities is crucial for effective clinical management. Transthoracic impedance cardiography (ICG) has been widely employed in assessing hemodynamic status in clinical settings. Given the limited research on the prognostic significance of ICG parameters in HF with permanent AF, we undertook this study. A total of 66 HF patients with permanent AF were included in this retrospective study, and the primary outcome was rehospitalization due to worsening HF within 180-day post-discharge. Cox regression analysis was performed to explore the connection between ICG-evaluated parameters and the outcome risk. Receiver operating characteristic (ROC) curve analysis determined the optimal cutoff values of risk factors, subsequently applied in plotting Kaplan Meier (KM) survival curves. Multivariate Cox regression analysis revealed that systemic vascular resistance (SVR) both on admission and at discharge independently predicted rehospitalization for worsening HF. ROC analysis established optimal SVR cutoff values: 320.89 (kPa s/L) on admission and 169.94 (kPa s/L) at discharge (sensitivity 70%, specificity 94.4%, area under the curve (AUC) 0.831, respectively, sensitivity 90%, specificity 55.6%, AUC 0.742). KM survival curves analysis showed that patients with SVR > 320.89 (kPa s/L) on admission had an 8.14-fold (P < 0.001) increased risk of the end-point event compared with those with SVR ≤ 320.89 (kPa s/L). Similarly, patients with SVR > 169.94 (kPa s/L) at discharge faced a risk elevated by 6.57 times (P = 0.002) relative to those with SVR ≤ 169.94 (kPa s/L). In HF patients with permanent AF, SVR measured by ICG emerges as an independent risk factor and clinical predictor for HF deterioration-related readmission within 180 days after discharge. Higher SVR levels, both upon admission and at discharge, correlate with an incremental rehospitalization risk. [ABSTRACT FROM AUTHOR]

Introduction: A multicenter prospective randomized controlled study was used to investigate the effect and safety of a new corneal wetting agent called the Corneal Surface Viscoelastic Protector (CsVisc, Success Bio-Tech Co., Ltd, China), on the corneal epithelium during ophthalmic surgery by comparison with the commercially available Cornea Protect (CP, Valeant Med Sp. zo. o. Leobendorf, Austria). Methods: This multicenter prospective randomized controlled study comprised patients scheduled for cataract surgery and pars plana vitrectomy. The patients were randomly assigned to receive either a new corneal wetting agent (CsVisc) or Cornea Protect (CP, Valeant Med Sp. zo. o. Leobendorf, Austria). Optical clarity during surgery, application frequency, duration of effect, diffusion time of corneal wetting agents, fluorescein staining, intraocular pressure (IOP), tear-film break-up time (TBUT), and Schirmer I test (SIT) were assessed. Adverse events were noted on the designated patient case report forms. Results: A total of 149 eyes (149 patients, mean age 62 years; range 25–80 years) were included in the study. There were 74 eyes in the control group and 75 eyes in the study group. In patients who underwent vitrectomy, the frequency of application was 1.62 ± 1.03 in the study group and 1.39 ± 0.66 in the control group, with no significant difference (P = 0.399), and the duration of effect was 19.16 ± 6.94 min in the study group and 19.06 ± 7.22 min in the control group, with no significant difference (P = 0.835). The optical clarity of the study group was not significantly different from that of the control group (P = 0.485). In patients who underwent cataract surgery, the frequency of application was 1.10 ± 0.38 in the study group and 1.07 ± 0.26 in the control group, and the difference was not significant (P = 0.950). The difference between the duration of effect in the study group (8.32 ± 2.50 min) and the control group (7.63 ± 2.52 min) was not significant (P = 0.310). The difference in optical clarity scores between the two groups was not statistically significant (P = 0.600). Among all patients in this study, the diffusion time of the corneal wetting agent was 14.97 ± 10.07 s in the control group and 11.23 ± 8.41 s in the study group, with a statistically significant difference (p = 0.008). The frequency of adverse events was 20.00% (15/75) in the study group and 14.86% (11/74) in the control group, with no statistically significant difference (P = 0.409). There were no serious adverse events related to the test medical device or causing patients to withdraw from the study. Conclusions: The CsVisc is safe and effective in preventing intraoperative corneal epithelial damage due to corneal dryness and can be comparable to the CP. In addition, the CsVisc has a shorter diffusion time. [ABSTRACT FROM AUTHOR]

Negative Poisson's ratio as the anomalous characteristic generally exists in artificial architectures, such as re‐entrant and honeycomb structures. The structures with negative Poisson's ratio have attracted intensive attention due to their unique auxetic effect and many promising applications in shear‐resistant and energy absorption fields. However, experimental observation of negative Poisson's ratio in natural materials barely happens, although various 2D layered materials are predicted in theory. Herein, the anisotropic Raman response and the intrinsic intralayer negative Poisson's ratio of 2D natural black arsenic (b‐As) via strain engineering strategy are reported. The results are evident by the detailed Raman spectrum of b‐As under uniaxial strain together with density functional theory calculations. It is found that b‐As is softer along the armchair than zigzag direction. The anisotropic mechanical features and van der Waals interactions play essential roles in strain‐dependent Raman shifts and negative Poisson's ratio in the natural b‐As along zigzag direction. This work may shed a light on the mechanical properties and potential applications of 2D puckered materials. [ABSTRACT FROM AUTHOR]

• CB2 receptors activation alleviates myocardial inflammation and damage in mice with sepsis. • Pyroptosis is inhibited during CB2 receptors activation in myocardium of septic mice. • Pyroptosis is an important signal pathway in the anti-inflammatory effect of CB2 receptors. It has been reported that cannabinoid receptors 2 (CB2 receptors) play an important role in the pathophysiological process of sepsis, which may also be associated with the regulation of pyroptosis, an inflammatory programmed cell death. The present study aimed to investigate the protective effect of CB2 receptors on myocardial damage in a model of septic mice by inhibiting pyroptosis. The C57BL/6 mice underwent cecal ligation and puncture (CLP) to induce sepsis. All mice were randomly divided into the sham, CLP, or CLP+HU308 group. Blood and heart tissue samples were collected 12 h after surgery. Hematoxylin and eosin staining was used for analyzing histopathological results. Creatine kinase isoenzymes (CK-MB) and IL-1β were measured using ELISA, while lactate dehydrogenase (LDH) level was determined using photoelectric colorimetry. The expression levels of CB2 receptors and pyroptosis-associated proteins (NLRP3, caspase-1, and GSDMD) were measured using western blotting. The location and distribution of CB2 receptors and caspase-1 in myocardial tissues were assessed by immunofluorescence. TUNEL staining was used to quantify the number of dead cells in myocardial tissues. The CLP procedure increased CB2 receptor expression in mice. CB2 receptors were located in myocardial macrophages. Activating CB2 receptors decreased the levels of myocardial damage mediator LDH, CK-MB, and inflammatory cytokine IL-1β. The results also showed that CLP increased the pyroptosis in myocardial tissues, while CB2 agonist HU308 inhibited pyroptosis by decreasing the level of NLRP3 and activating caspase-1 and GSDMD. CB2 receptor activation has a protective effect on the myocardium of mice with sepsis by inhibiting pyroptosis. [ABSTRACT FROM AUTHOR]

The research presented in this paper introduces a novel environmental energy‐harvesting technology that harnesses electricity from the evaporation of water using porous structural materials. Specifically, a strategy employing paper‐based hydroelectric generators (p‐HEGs) is proposed to capture the energy produced during water evaporation and convert it into usable electricity. The p‐HEGs offer several advantages, including simplicity in fabrication, low cost, and reusability. To evaluate their effectiveness, the water evaporation‐induced electrical output performance of four different p‐HEGs are compared. Among the variants tested, the p‐HEG combining wood pulp and polyester fiber exhibits the best output performance. At room temperature, this particular p‐HEG generates a short‐circuit current and open‐circuit voltage of ≈0.4 µA and 0.3 V, respectively, thereby demonstrating excellent electrical stability. Furthermore, the electrical current and voltage generated by the p‐HEG through water evaporation are able to power an LED light, both individually and in series and parallel connections. This study delves into the potential of electricity harvesting from water evaporation and establishes it as a viable method for renewable energy applications. [ABSTRACT FROM AUTHOR]

Aim: The pathogenesis of ankylosing spondylitis (AS) seems to be associated with genetics, the environment, heredity, and oxidative stress. Single nucleotide polymorphisms (SNPs) in the displacement loop (D‐loop) region of mitochondrial DNA (mtDNA) and mtDNA copy number were investigated for their correlation with AS patients. Methods: This study included 83 AS patients and 100 healthy controls from the Second Hospital of Hebei Medical University. DNAs were extracted from blood samples for polymerase chain reaction analysis and quantitative real‐time polymerase chain reaction analysis. Plasma reactive oxygen species (ROS) levels were measured by fluorescent probe technology. Results: The distribution frequencies of the minor alleles of nucleotides 16304C (p =.037), 16311C (p =.027), and 152C (p =.034) were remarkably higher in AS patients than in healthy controls, which indicated that the16304C, 16311C, and 152C alleles were correlated with an increased risk of AS. Simultaneously, mtDNA copy number was statistically higher in patients with AS compared with controls (1.450 ± 0.876 versus 0.835 ± 0.626, p <.001). We also observed an increased ROS generation in AS patients compared with controls (27 066.169 ± 18 364.819 versus 14 758.330 ± 5854.946, p <.001) subsequently. In addition, the AS susceptible SNP 16311C is associated with high ROS levels (35 065.177 ± 26 999.934 vs. 25 005.818 ± 14 999.495, p =.043). Conclusion: Our study demonstrated that SNPs in the mtDNA D‐loop could be AS risk biomarkers with the potential to promote oxidative stress levels; mtDNA copy number‐induced mitochondrial dysfunction may also be involved in AS pathogenesis. [ABSTRACT FROM AUTHOR]

Recent studies have shed light on the potential of circular RNA (circRNA) as a biomarker for disease diagnosis and as a nucleic acid vaccine. The exploration of these functionalities requires correct circRNA full-length sequences; however, existing assembly tools can only correctly assemble some circRNAs, and their performance can be further improved. Here, we introduce a novel feature known as the junction contig (JC), which is an extension of the back-splice junction (BSJ). Leveraging the strengths of both BSJ and JC, we present a novel method called JCcirc (https://github.com/cbbzhang/JCcirc). It enables efficient reconstruction of all types of circRNA full-length sequences and their alternative isoforms using splice graphs and fragment coverage. Our findings demonstrate the superiority of JCcirc over existing methods on human simulation datasets, and its average F1 score surpasses CircAST by 0.40 and outperforms both CIRI-full and circRNAfull by 0.13. For circRNAs below 400 bp, 400–800 bp, 800 bp–1200 bp and above 1200 bp, the correct assembly rates are 0.13, 0.09, 0.04 and 0.03 higher, respectively, than those achieved by existing methods. Moreover, JCcirc also outperforms existing assembly tools on other five model species datasets and real sequencing datasets. These results show that JCcirc is a robust tool for accurately assembling circRNA full-length sequences, laying the foundation for the functional analysis of circRNAs. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) is becoming one of the most important RNA modifications in plant growth and development, including defense, cell differentiation, and secondary metabolism. YT521-B homology (YTH) domain-containing RNA-binding proteins, identified as m6A readers in epitranscriptomics, could affect the fate of m6A-containing RNA by recognizing and binding the m6A site. Therefore, the identification and study of the YTH gene family in Liriodendron chinense (L. chinense) can provide a molecular basis for the study of the role of m6A in L. chinense, but studies on the YTH gene in L. chinense have not been reported. We identified nine putative YTH gene models in the L. chinense genome, which can be divided into DF subgroups and DC subgroups. Domain sequence analysis showed that the LcYTH protein had high sequence conservation. A LcYTH aromatic cage bag is composed of tryptophan and tryptophan (WWW). PrLDs were found in the protein results of YTH, suggesting that these genes may be involved in the process of liquid–liquid phase separation. LcYTH genes have different tissue expression patterns, but the expression of LcYTHDF2 is absolutely dominant in all tissues. In addition, the expression of the LcYTH genes is changed in response to ABA and MeJA. In this study, We identified and analyzed the expression pattern of LcYTH genes. Our results laid a foundation for further study of the function of the LcYTH gene and further genetic and functional analyses of m6A RNA modification in forest trees. [ABSTRACT FROM AUTHOR]

To date, all explicit symplectic Runge–Kutta–Nyström methods of order five or above are derived by numerical solutions of order condition equations and symplectic condition. In this paper, we derive 124 sets of seven-stage fifth-order explicit symplectic Runge–Kutta–Nyström methods with closed-form coefficients in the Butcher tableau using the roots of a degree-3 shifted Legendre polynomial. One method is analyzed and its P-stable interval is derived. Numerical tests on the two newly discovered methods are performed, showing their long-time stability and large step size stability over some existing methods. [ABSTRACT FROM AUTHOR]

None-Line-of-Sight (NLOS) propagation of Ultra-Wideband (UWB) signals leads to a decrease in the reliability of positioning accuracy. Therefore, it is essential to identify the channel environment prior to localization to preserve the high-accuracy Line-of-Sight (LOS) ranging results and correct or reject the NLOS ranging results with positive bias. Aiming at the problem of the low accuracy and poor generalization ability of NLOS/LOS identification methods based on Channel Impulse Response (CIR) at present, the multilayer Convolutional Neural Networks (CNN) combined with Channel Attention Module (CAM) for NLOS/LOS identification method is proposed. Firstly, the CAM is embedded in the multilayer CNN to extract the time-domain data features of the original CIR. Then, the global average pooling layer is used to replace the fully connected layer for feature integration and classification output. In addition, the public dataset from the European Horizon 2020 Programme project eWINE is used to perform comparative experiments with different structural models and different identification methods. The results show that the proposed CNN-CAM model has a LOS recall of 92.29%, NLOS recall of 87.71%, accuracy of 90.00%, and F1-score of 90.22%. Compared with the current relatively advanced technology, it has better performance advantages. [ABSTRACT FROM AUTHOR]

The development of enhanced strategies with excellent biocompatibility is critical for electrochemiluminescence (ECL) imaging of single cells. Here, we report an ECL imaging technique for a single cell membrane protein based on a Co3O4 nanozyme catalytic enhancement strategy. Due to the remarkable catalytic performance of Co3O4 nanozymes, H2O2 can be efficiently decomposed into reactive oxygen radicals, and the reaction with L012 was enhanced, resulting in stronger ECL emission. The anti-carcinoembryonic antigen (CEA) was coupled with nanozyme particles to construct a probe that specifically recognized the overexpressed CEA on the MCF-7 cell membrane. According to the locally enhanced visualized luminescence, the rapid ECL imaging of a single cell membrane protein was eventually realized. Accordingly, Co3O4 nanozymes with highly efficient activity will provide new insights into ECL imaging analysis of more biological small molecules and proteins. [ABSTRACT FROM AUTHOR]

In this study, we aimed to explore the potential targets and functional mechanisms of Rk1 combined with Rg5 (Rk1+Rg5) against type II diabetes mellitus (T2DM). Network pharmacology and molecular docking were used to predict and verify the targets and signaling pathways of Rk1+Rg5 against T2DM. The results were further confirmed by a db/db mouse model and a model using PA-induced L6 cells. According to network pharmacology, a total of 250 core targets of Rk1+Rg5 towards T2DM were identified; the insulin resistance signaling pathways were enriched by KEGG. Results of molecular docking indicated good binding affinity of Rk1 and Rg5 to Akt1. In vivo and in vitro studies further showed that Rk1+Rg5 is an inhibitor of skeletal muscle insulin resistance. The results showed that Rk1+Rg5 significantly improved the hyperglycemic state of db/db mice, alleviated dyslipidemia, and promoted skeletal muscle glucose uptake. This phenomenon was closely related to the alleviation of the insulin resistance in skeletal muscles. Finally, the combination activated the Akt signaling pathway and promoted GLUT4 translocation to the cell membrane for glucose uptake. Altogether, our findings, for the first time, demonstrate that the combination of Rk1 and Rg5 could be beneficial for anti-T2DM, possibly involving ameliorated insulin resistance. [ABSTRACT FROM AUTHOR]

Necroptosis is a newly discovered mechanism of cell death, and its key regulatory role is attributed to the interaction of receptor-interacting protein kinases (RIPKs) RIPK1 and RIPK3. Ca2+/calmodulin-dependent protein kinase (CaMKII) is a newly discovered RIPK3 substrate, and its alternative splicing plays a fundamental role in cardiovascular diseases. In the present study, we aimed to explore the role and mechanism of necroptosis and alternative splicing of CaMKIIδ in myocardial hypertrophy. Transverse aortic constriction (TAC) was performed on wild-type and knockout mice to establish the model of myocardial hypertrophy. After 3 weeks, echocardiography, cardiac index, cross-sectional area of myocardial cells, hypertrophic gene expression, myocardial damage, and fibers were assessed. Moreover, we detected the levels of inflammatory factors (IL-6 and TNF-α) and examined the expressions of necroptosis-related proteins RIPK3, RIPK1, and phosphorylated MLKL. Meanwhile, we tested the expression levels of splicing factors ASF/SF2 and SC-35 in an attempt to explore CaMKII δ. The relationship between variable splicing disorder and the expression levels of splicing factors ASF/SF2 and SC-35. Further, we also investigated CaMKII activation, oxidative stress, and mitochondrial ultrastructure. In addition, wild-type mice were administered with a recombinant adeno-associated virus (AAV) carrying RIPK3, followed by TAC surgery to construct a model of myocardial hypertrophy, and the above-mentioned indicators were tested after 3 weeks. The results showed that RIPK3 deficiency could alleviate cardiac dysfunction, myocardial injury, aggravation of necrosis, and CaMKII activation induced by TAC surgery in mice with myocardial hypertrophy. Tail vein injection of AAV could reverse cardiac dysfunction, myocardial damage, aggravation of necrosis, and CaMKII activation in mice with myocardial hypertrophy. These results proved that RIPK3 could be used as a molecular intervention target for the prevention and treatment of myocardial hypertrophy. [ABSTRACT FROM AUTHOR]

This study aimed to explore the effects of different starch source diets on the growth performance and hepatopancreas RNA-seq of grass carp. Juvenile grass carp (initial body weight of 39.4 ± 1.6 g) were fed diets containing 25% corn (CO), potato (PO), and wheat (WH) starch for 8 weeks, respectively. The weight gain ratio (WGR) was significantly lower, whereas the visceral somatic index (VSI) and feed conversion ratio (FCR) were significantly higher in the CO group than those in the PO and WH groups. These indicators did not significantly differ between the PO and WH groups. Hepatopancreas RNA-seq analysis showed that 536, 514, and 647 differentially expressed genes (DEGs) were screened out in the comparisons of PO vs. WH, PO vs. CO, and CO vs. WH. The DEGs were mainly enriched in the several known pathways involved in steroid biosynthesis, cell cycle, fatty acid metabolism, and fat digestion and absorption according to Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The major DEGs related to lipid and carbohydrate metabolism were analyzed, in which lipogenesis-related DEGs (fasn, acc1, scd1, elovl6, and me1), fat digestion and absorption-related DEGs (fabp7, apoa1, apoa4, and pla2), and glycometabolism-related DEGs (gk, g6pd, and pepck) were down-regulated in the PO group compared with those in the CO and WH groups. Conversely, steroid synthesis-related DEGs (hmgcs, fdft1, sqle, lss, cyp51, msmo1, nsdhl, ugt, cyp1b1, and cyp7a1) were up-regulated in the PO group. These results indicate that the long-term PO ingestion could modulate hepatic lipid metabolism by reducing fatty acid biosynthesis and increasing bile acid biosynthesis. PO may be healthier in contrast to CO alone, which may not be suitable as a starch source in grass carp diet. [ABSTRACT FROM AUTHOR]

Vitamin D‐regulating action of PPARγ on obesity has been confirmed on adipocyte differentiation. However, it is not clear whether vitamin D affects the morphological size of mature adipocytes by influencing the expression of PPARγ in vivo. Our hypothesis was that Vitamin D3 (VitD3) inhibits the growth of adipocyte size by suppressing PPARγ expression in white adipocytes of obese mice. Five‐week‐old male C57BL/6J mice were randomly divided into normal diet and high‐fat diet groups. After 10 weeks, the body weight between the two groups differed by 26.91%. The obese mice were randomly divided into a high‐fat diet, solvent control, low‐dose VitD3 (5000 IU/kg·food), medium‐dose VitD3 (7500 IU/kg·food), high‐dose VitD3 (10,000 IU/kg·food), and PPAR γ antagonist group, and the intervention lasted for 8 weeks. Diet‐induced obesity (DIO) mice fed high‐dose VitD3 exacerbated markers of adiposity (body weight, fat mass, fat mass rate, size of white and brown adipocytes, mRNA, and protein levels of ATGL and Fsp27), and the protein level of ATGL and Fsp27 decreased in the low‐dose group. In conclusion, high‐dose VitD3 possibly via inhibiting the ATGL expression, thereby inhibiting lipolysis, increasing the volume of adipocytes, and decreasing their fat‐storing ability resulted in decreased Fsp27 expression. Therefore, long‐term high‐dose oral VitD3 may not necessarily improve obesity, and we need more clinical trials to explore the intervention dose and duration of VitD3 in the treatment of VitD3 deficiency in obese patients. [ABSTRACT FROM AUTHOR]

Water evaporation is a ubiquitous natural process for collecting thermal energy from the environment. Carbon nanomaterial‐based aerogels are good candidates for use as hydroelectric generators (HEGs), permitting substantial interaction with water through electronic coupling, and have been considered for application in evaporation‐induced electricity generation. However, the water transport and electricity generation ability of the aerogels are affected by their pore structures. Inspired by the directional transport of the water vessel elements of the xylem, a biomimetic partially reduced graphene oxide aerogel (prGO) with an aligned porous structure is prepared, assisted by directional ice templating. The as‐prepared prGO aerogel presents a high capillary water transport rate and can efficiently transport water to the top, which is the basis for efficient current generation. This biomimetic prGO is scalable, providing an avenue for assembling other low‐dimensional carbon materials into high current output HEGs. [ABSTRACT FROM AUTHOR]

Background: Thymidylate synthase (TYMS) is involved in the malignant process of multiple cancers, and has gained much attention as a cancer treatment target. However, the mechanism in carcinogenesis of esophageal squamous cell cancer (ESCC) is little reported. The present study was to clear the biological roles and carcinogenic mechanism of TYMS in ESCC, and explored the possibility to use TYMS as a tumor marker in diagnosis and a drug target for the treatment of ESCC. Methods: Stably TYMS-overexpression cells established by lentivirus transduction were used for the analysis of cell proliferation. RNA sequencing was performed to explore the possible carcinogenic mechanisms. Results: GEPIA databases analysis showed that TYMS expression in esophageal cancer tissues was higher than that in normal tissues. The MTT assay, colony formation assay, and nude mouse subcutaneous tumor model found that the overexpression of TYMS increased cell proliferation. Transcriptome sequencing analysis revealed that the promoted cell proliferation in TYMS-overexpression ESCC cells were mediated through activating genes expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2 dependent antioxidant enzymes to relieve oxidative stress, which was confirmed by increased glutathione (GSH), glutathione peroxidase (GPX) activities, and reduced reactive oxygen species. Nrf2 active inhibitors (ML385) used in TYMS-overexpression cells inhibited the expression of Nrf2-dependent antioxidant enzyme genes, thereby increasing oxidative stress and blocking cell proliferation. Conclusion: Our study indicated a novel and effective regulatory capacity of TYMS in the cell proliferation of ESCC by relieving oxidative stress through activating expression of Nrf2 and Nrf2-dependent antioxidant enzymes genes. These properties make TYMS and Nrf2 as appealing targets for ESCC clinical chemotherapy. [ABSTRACT FROM AUTHOR]

In this study, five new chitosan oligosaccharide quaternary ammonium derivatives bearing quinoline are synthesized by reaction between 6‐O‐chloroacetyl‐2‐N, N, N‐trimethyl quaternary ammonium salt chitosan oligosaccharide (CTCOS, compound 1) and quinoline derivatives. The derivatives are characterized by analytical techniques including Fourier Transform Infrared (FTIR), 1H Nuclear Magnetic Resonance (1H NMR) spectroscopy, and elemental analysis. The obtained results confirm that quinoline groups are successfully introduced into the CTCOS molecule. Meanwhile, the antioxidant activities of the prepared chitosan oligosaccharide derivatives are evaluated in vitro. The experimental results show that the derivatives have excellent free radical scavenging ability. The free radical scavenging abilities are all over 75% at the concentration of 1.6 mg mL−1. Moreover, antibacterial tests show that derivative 2e has the best antibacterial activities. Its minimum inhibitory concentration (MIC) value and minimum bactericidal concentration (MBC) value against Staphylococcus aureus and Escherichia coli are 0.0625 and 0.03125 mg mL−1, respectively. In addition, the cytotoxicity of chitosan oligosaccharide and its derivatives is examined by MTT colorimetric assay in RAW 264.7 macrophages, observing that all derivatives are non‐cytotoxic. Consequently, the findings indicate that the enhanced antioxidant activity, antibacterial activity, and biocompatibility of these chitosan oligosaccharide derivatives can enlarge the scope of the application of chitosan oligosaccharides, particularly as antioxidant and antibacterial agents in food packaging, pharmaceutical, cosmetics industries, and other fields. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic poses a disruptive impact on public health and the global economy. Fortunately, the development of COVID-19 vaccines based on in vitro-transcribed messenger RNA (IVT mRNA) has been a breakthrough in medical history, benefiting billions of people with its high effectiveness, safety profile, and ease of large-scale production. This success is the result of decades of continuous RNA research, which has led to significant improvements in the stability and expression level of IVT mRNA through various approaches such as sequence optimization and improved preparation processes. IVT mRNA sequence optimization has been shown to have a positive effect on enhancing the mRNA expression level. The innovation of IVT mRNA purification technology is also indispensable, as the purity of IVT mRNA directly affects the success of downstream vaccine preparation processes and the potential for inducing unwanted side effects in therapeutic applications. Despite the progress made, challenges related to IVT mRNA sequence design and purification still require further attention to enhance the quality of IVT mRNA in the future. In this review, we discuss the latest innovative progress in IVT mRNA design and purification to further improve its clinical efficacy. [ABSTRACT FROM AUTHOR]

Since there are many SNPs in this region in humans, we will not be surprised that those SNPs with more sizeable side chains might also disrupt the enzyme activity and be implicated in metabolic disorders and abnormal drug metabolism, and therefore, should be considered for precision medicine. Dear Editor, Cytochrome P450s (CYPs) are a superfamily of heme-containing enzymes that play critical roles in oxidizing endogenous metabolites and xenobiotics.[1] They are membrane-anchored enzymes, and the transmembrane domains are involved in the electron transfer and the access of substrate and water during the catalytic cycle.[[2], [4]] Mutations of human CYPs cause metabolic disorders and abnormal drug metabolism.[5] Because their amino acid sequences are remarkably diverse, the existing work on different human CYPs is seemingly unrelated. (A-C) The enzyme activities of the wild-type (WT) and mutants of CYP21A2 (A), CYP7A1 (B), and CYP2A6 (C) were revealed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Metabolic profiling showed that the conversion of Gly to Ala in both positions of the I-helix kink (G292A and G293A) reduced CYP21A2 activity to about 60% of the WT activity, whereas substituents with more sizeable side chains more profoundly inhibited the enzyme function. [Extracted from the article]

A major bottleneck of distributed learning under parameter server (PS) framework is communication cost due to frequent bidirectional transmissions between the PS and workers. To address this issue, local stochastic gradient descent (SGD) and worker selection have been exploited by reducing the communication frequency and the number of participating workers at each round, respectively. However, partial participation can be detrimental to convergence rate, especially for heterogeneous local datasets. In this paper, to improve communication efficiency and speed up the training process, we develop a novel worker selection strategy named AgeSel. The key enabler of AgeSel is utilization of the ages of workers to balance their participation frequencies. The convergence of local SGD with the proposed age-based partial worker participation is rigorously established. Simulation results demonstrate that the proposed AgeSel strategy can significantly reduce the number of training rounds needed to achieve a targeted accuracy, as well as the communication cost. The influence of the algorithm hyper-parameter is also explored to manifest the benefit of age-based worker selection. [ABSTRACT FROM AUTHOR]

Industrial-robot assisted abrasive cloth wheel polishing blades aim to reduce surface roughness and improve machining consistency of blades. Since the blade is the complex free-form surface, the blade surface after offline programming has "over-polishing," "under-polishing," and machining allowance uneven phenomenon. In this paper, fuzzy impedance force control technology is proposed to solve the precision problem in the blade polishing process. First, the position-based impedance control algorithm is analyzed, and reasonable impedance parameters are obtained based on the actual robot model. Then, the fuzzy variable impedance control combining fuzzy theory and impedance control is proposed to solve the problems of poor trajectory tracking ability and force instability, when the traditional impedance control faces environmental changes and unknown environments. Finally, the simulation platform is built with the help of MATLAB Simulink tool to verify the effectiveness and rationality of the strategy, and the comparative experiment is conducted for robot-assisted abrasive cloth wheel polishing blade under fuzzy variable impedance force control and without force control. The results show that after superimposing the displacement compensation controlled by the fuzzy variable impedance force on the blade surface, the blade surface roughness is below 0.4 μm, the polishing machining allowance is within ± 0.06 mm, and the uniformity and consistency of the blade polishing surface are better. [ABSTRACT FROM AUTHOR]

The accelerated energy supply of co-reactants is an extremely effective strategy for achieving highly sensitive electrochemiluminescence analysis, and binary metal oxides would be an excellent tool for this purpose owing to the nano-enzyme acceleration of mixed metal valence states. Herein, an electrochemiluminescent (ECL) immunosensor for monitoring the concentration of cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) was developed based on a co-amplification strategy triggered by two bimetallic oxides, CoCeOx and NiMnO3, with luminol as the luminophore. CoCeOx derived from an MOF exhibits a large specific surface area and excellent loading capacity as a sensing substrate, and the peroxidase properties enable the catalysis of hydrogen peroxide to provide energy supply to the underlying radicals. The dual enzymatic properties of flower-like NiMnO3 were employed as probe carriers for luminol enrichment. The peroxidase properties built on Ni2+/Ni3+ and Mn3+/Mn4+ binary redox pairs resulted in the integration of highly oxidative hydroxyl radicals, and the oxidase properties provided additional superoxide radicals via dissolved oxygen. The practically proven multi-enzyme-catalyzed sandwich-type ECL sensor easily accomplished an accurate immunoassay of CYFRA21-1, harvesting a detection limit of 0.3 pg mL−1 in the linear range of 0.001–150 ng mL−1. In conclusion, this work explores the cyclic catalytic amplification of mixed-valence binary metal oxides with nano-enzyme activity in the field of ECL and develops an effective pathway for ECL immunoassay. [ABSTRACT FROM AUTHOR]

Agricultural poly-γ-glutamic acid (γ-PGA) and γ-PGA super absorbent polymer (SAP) are two forms of γ-PGA applied in agriculture. Different quantities of γ-PGA and γ-PGA SAP (40 kg/hm2, 80 kg/hm2, 120 kg/hm2 and 160 kg/hm2) were applied to the soil in order to investigate their effects on the microenvironment of soil root zone and the yield of winter wheat. The soil water content increased with increasing amounts of γ-PGA SAP. The content of nitrate nitrogen and ammonium nitrogen increased with the increasing amounts of γ-PGA, while γ-PGA SAP significantly increased the content of ammonium nitrogen. The number of soil microorganisms and soil enzyme activities in the root zone increased with the addition of γ-PGA and γ-PGA SAP. The yield of winter wheat increased with the addition of γ-PGA or γ-PGA SAP, but the increasing rate decreased when the amount of γ-PGA and γ-PGA SAP exceeded 80 kg/hm2, with increases of 5.95% and 6.77% compared to the control group, respectively. The addition of γ-PGA significantly increased the protein content of wheat grains, and the WUE increased with increasing amounts of γ-PGA and γ-PGA SAP. [ABSTRACT FROM AUTHOR]

The ion channels in sperm tail play an important role in triggering key physiological reactions, e.g., progressive motility, hyperactivation, required for successful fertilization. Among them, CatSper and KSper have been shown to be important ion channels for the transport of Ca2+ and K+. Moreover, the voltage‐gated proton channel Hv1, the sperm‐specific sodium‐hydrogen exchanger (sNHE), the epithelial sodium channel (ENaC), members of the temperature‐sensitive TRP channel family, and the cystic fibrosis transmembrane regulator (CFTR) are also found in the flagellum. This review focuses on the latest advances in ion channels located at the flagellum, describes how they affect sperm physiological function, and summarizes some primary mutual regulation mechanism between ion channels, including PH, membrane potential, and cAMP. These ion channels may be promising targets for clinical application in infertility. [ABSTRACT FROM AUTHOR]

Abstract Flavonoid compounds exhibit a wide range of health benefits as plant-derived dietary components. Typically, co-consumed with the food matrix,they must be released from the matrix and converted into an absorbable form (bioaccessibility) before reaching the small intestine, where they are eventually absorbed and transferred into the bloodstream (bioavailability) to exert their biological activity. However, a large number of studies have revealed the biological functions of individual flavonoid compounds in different experimental models, ignoring the more complex but common relationships established in the diet. Besides, it has been appreciated that the gut microbiome plays a crucial role in the metabolism of flavonoids and food substrates, thereby having a significant impact on their interactions, but much progress still needs to be made in this area. Therefore, this review intends to comprehensively investigate the interactions between flavonoids and food matrices, including lipids, proteins, carbohydrates and minerals, and their effects on the nutritional properties of food matrices and the bioaccessibility and bioavailability of flavonoid compounds. Furthermore, the health effects of the interaction of flavonoid compounds with the gut microbiome have also been discussed. HIGHLIGHTS Flavonoids are able to bind to nutrients in the food matrix through covalent or non-covalent bonds. Flavonoids affect the digestion and absorption of lipids, proteins, carbohydrates and minerals in the food matrix (bioaccessibility). Lipids, proteins and carbohydrates may favorably affect the bioavailability of flavonoids. Improved intestinal flora may improve flavonoid bioavailability. Flavonoids are able to bind to nutrients in the food matrix through covalent or non-covalent bonds.Flavonoids affect the digestion and absorption of lipids, proteins, carbohydrates and minerals in the food matrix (bioaccessibility).Lipids, proteins and carbohydrates may favorably affect the bioavailability of flavonoids.Improved intestinal flora may improve flavonoid bioavailability. [ABSTRACT FROM AUTHOR]

A novel and reusable electrochemiluminescence biosensor was developed based on tetrahedral DNA (TDN) signal amplification for ultrasensitive detection of miRNA-27a. The flowered nickel-iron layered double hydroxide@AuNPs (NiFe-LDH@AuNPs) composites increase the amount of hairpin DNA fixed on the electrode. When miRNA is present, TDN-Ru(bpy)32+ acts as an ECL probe, forming a stable sandwich structure with miRNA-27a and hairpin DNA through base complementation pairing, thus achieving miRNA detection. This biosensor has the characteristics of high sensitivity, excellent selectivity, and good reproducibility. [ABSTRACT FROM AUTHOR]

The mortality rate of epithelial ovarian cancer (EOC) remains the first in malignant tumors of the female reproductive system. The characteristics of rapid proliferation, extensive implanted metastasis, and treatment resistance of cancer cells require an extensive metabolism rewiring during the progression of cancer development. EOC cells satisfy their rapid proliferation through the rewiring of perception, uptake, utilization, and regulation of glucose, lipids, and amino acids. Further, complete implanted metastasis by acquiring a superior advantage in microenvironment nutrients competing. Lastly, success evolves under the treatment stress of chemotherapy and targets therapy. Understanding the above metabolic characteristics of EOCs helps to find new methods of its treatment. [ABSTRACT FROM AUTHOR]

To improve the corrosion resistance of Al2O3-13 wt.% TiO2 (AT13) coatings prepared by plasma spraying, CaO-MgO-Al2O3-SiO2 silicate glass powder was mixed with AT13 in different proportions (Glass/AT13 = 0/10, 1/10, 2/10 and 3/10, by mass). The morphology and structure of the coatings were characterized by field emission scanning electron microscopy/energy spectrometry, x-ray diffraction and confocal laser scanning microscopy. Their corrosion resistance was evaluated by immersion corrosion and electrochemical corrosion tests. The results show that the glass-doped composite coatings have lower porosity, higher microhardness and lower roughness than the pure AT13 coating. Therefore, the glass-doped coatings exhibited better corrosion resistance than the sealed AT13 coating. In addition, the composite coating with the doping ratio of 2:10 maintained the best overall corrosion resistance with low corrosion zones, low corrosion current values, high pitting potential and high polarization resistance. Therefore, the proper addition of glass frit, with its excellent characteristics of low viscosity and high fluidity at high temperatures during plasma spraying, can fully compensate for the high porosity of ceramic coatings. Proper doping with glass has excellent potential application to improve the corrosion resistance and service performance of plasma-sprayed ceramic coatings. [ABSTRACT FROM AUTHOR]

Aim: Multiple sclerosis (MS) is an autoimmune disease, and its typical characteristics are neuroinflammation and the demyelination of neurons in the central nervous system (CNS). Sterile alpha and TIR motif containing 1 (SARM1) is an essential factor mediating axonal degeneration and SARM1 deletion reduces the neuroinflammation in spinal cord injury. This study aimed to explore the roles of SARM1 and its underlying mechanisms in MS. Methods: Experimental autoimmune encephalomyelitis (EAE, a model of MS) model was established. Immunostaining, western blot, electron microscope, and HE staining were used to examine the pathological manifestations such as inflammation, demyelination, and neuronal death in SARM1f/f EAE mice and SARM1Nestin‐CKO EAE mice. In addition, RNA‐seq, real‐time PCR and double‐immunostaining were used to examine the underlying mechanism of SARM1 in EAE mice. Results: SARM1 was upregulated in neurons of the spinal cords of EAE mice. SARM1 knockout in CNS ameliorated EAE with less neuroinflammation, demyelination, and dead neurons. Mechanically, SARM1 knockout resulted in the reduction of insulin‐like growth factor (IGF)‐binding protein 2 (IGFBP2) in neurons of EAE mice, which might inhibit the neuroinflammation through inhibiting NF‐κB signaling. Finally, activation of NF‐κB partially aggravated the neuroinflammation and demyelination deficits of SARM1Nestin‐CKO EAE mice. Conclusions: These results identified the unknown role of SARM1 in the promotion of neuroinflammation and demyelination and revealed a novel drug target pathway of SARM1/IGFBP2/NF‐κB for MS. [ABSTRACT FROM AUTHOR]

The majority of patients are diagnosed when ovarian cancer (OC) has metastasized, making surgery and chemotherapy less effective. Thus, there is an urgent need to elucidate the mechanisms underlying metastasis and to further explore novel diagnostic biomarkers of OC metastasis. Here, we conducted a genome-wide CRISPR-Cas9 screen for anoikis resistance to identify key genes associated with OC metastasis. Further, bioinformatic analysis was performed using TCGA and GTEx datasets to explore the genes associated with OC progression and prognosis. After integrated analysis, the V-set and transmembrane domain-containing protein 2-like (VSTM2L) was identified as a crucial gene closely associated with OC metastasis, progression, and prognosis. Further validation using a patient-based cohort suggested that VSTM2L expression was significantly higher in metastatic lesions than in primary lesions. Subsequently, an in vitro assay showed that VSTM2L silencing increased SKOV3 cell death and hampered spheroid formation. Mechanistically, GSEA highlighted that epithelial-mesenchymal transition (EMT)-related pathways was positively associated with VSTM2L expression. Consistently, the validation based on the VSTM2L silence suggested the involvement of VSTM2L in EMT-related TGF-β and NF-κB signaling. Meanwhile, the addition of VSTM2L-containing medium did not provoke those signaling, indicating VSTM2L functions as an intracellular protein to activate TGF-β and NF-κB signaling. In summary, our study revealed that VSTM2L is a novel player involved in anoikis resistance and is a promising biomarker of OC metastasis and prognosis. • Genome-wide screening combined with bioinformatics identified VSTM2L as a promising biomarker for ovarian cancer. • VSTM2L regulates TGF-β and NF-κB signaling and promotes anoikis resistance. • VSTM2L functions as an intracellular protein to regulate EMT-related signaling. [ABSTRACT FROM AUTHOR]