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Air pollution has a significant global impact on natural resources and public health. Accurate prediction of air pollution is crucial for effective prevention and control measures. However, due to regional variations, different cities may have varying primary pollutants, posing new challenges for accurate prediction. In this paper, we propose a novel method called FP-RF, which integrates clustering algorithms to categorize multiple cities according to their air quality index values. Subsequently, we apply functional principal component analysis to extract the primary components of air pollution within each cluster. Furthermore, an enhanced random forest algorithm is utilized to predict air quality grades for each city. We conduct experimental evaluations using authentic historical data from Anhui Province spanning from 2018 to 2023. The results unequivocally establish the effectiveness of our model, with an average accuracy rate of 98.6% in forecasting six pollution grades and 96.04% accuracy in predicting 16 prefecture-level cities, surpassing performance compared to other baseline models., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The tire rubber antioxidant N -(1,3-dimethylbutyl)- N' -phenyl- p -phenylenediamine (6PPD) and its quinone product (6PPDQ) are prevalent emerging contaminants, yet their biotransformation profiles remain poorly understood, hampering the assessment of environmental and health risks. This study investigated the phase-I metabolism of 6PPD and 6PPDQ across aquatic and mammalian species through in vitro liver microsome (LM) incubations and in silico simulations. A total of 40 metabolites from seven pathways were identified using the highly sensitive nano-electrospray ionization mass spectrometry. Notably, 6PPDQ was consistently detected as a 6PPD metabolite with an approximate 2% yield, highlighting biotransformation as a neglected indirect exposure pathway for 6PPDQ in organisms. 6PPDQ was calculated to form through a facile two-step phenyl hydroxylation of 6PPD, catalyzed by cytochrome P450 enzymes. Distinct species-specific metabolic kinetics were observed, with fish LM demonstrating retarded biotransformation rates for 6PPD and 6PPDQ compared to mammalian LM, suggesting the vulnerability of aquatic vertebrates to these contaminants. Intriguingly, two novel coupled metabolites were identified for 6PPD, which were predicted to exhibit elevated toxicity compared to 6PPDQ and result from C-N oxidative coupling by P450s. These unveiled metabolic profiles offer valuable insights for the risk assessment of 6PPD and 6PPDQ, which may inform future studies and regulatory actions.

Chronic hyperglycaemia is a chief feature of diabetes mellitus and complicates with many systematic anomalies. Non-human primates (NHPs) are excellent for studying hyperglycaemia or diabetes and associated comorbidities, but lack behavioural observation. In the study, behavioural, brain imaging and histological analysis were performed in a case of spontaneously hyperglycaemic (HGM) Macaca fascicularis. The results were shown that the HGM monkey had persistent body weight loss, long-term hyperglycaemia, insulin resistance, dyslipidemia, but normal concentrations of insulin, C-peptide, insulin autoantibody, islet cell antibody and glutamic acid decarboxylase antibody. Importantly, an impaired working memory in a delayed response task and neurological dysfunctions were found in the HGM monkey. The tendency for atrophy in hippocampus was observed by magnetic resonance imaging. Lenticular opacification, lens fibres disruptions and vacuole formation also occurred to the HGM monkey. The data suggested that the spontaneous HGM monkey might present diabetes-like characteristics and associated neurobehavioral anomalies in this case. This study first reported cognitive deficits in a spontaneous hyperglycaemia NHPs, which might provide evidence to use macaque as a promising model for translational research in diabetes and neurological complications., (© 2024 John Wiley & Sons Australia, Ltd.)

In the genomics of plants and the phytoecosystem, Pyrus (pear) is among the most nutritious fruits and contains fiber that has great health benefits to humans. It is mostly cultivated in temperate regions and is one of the most cultivated pome fruits globally. Pears are highly subjected to biotic and abiotic stresses that affect their yield. TIR1/AFB proteins act as auxin co-receptors during the signaling of nuclear auxins and play a primary role in development-related regulatory processes and responses to biotic and abiotic stresses. However, this gene family and its members have not been explored in Pyrus genomes, and understanding these genes will help obtain useful insights into stress tolerance and ultimately help maintain a high yield of pears. This study reports a pangenome-wide investigation of TIR1/AFB genes from eight Pyrus genomes: Cuiguan ( Pyrus pyrifolia ), Shanxi Duli ( P. betulifolia ), Zhongai 1 [( P. ussuriensis × communis ) × spp.], Nijisseiki ( P . pyrifolia ), Yunhong No.1 ( P . pyrifolia ), d'Anjou ( P. communis ), Bartlett v2.0 ( P. communis ), and Dangshansuli v.1.1 ( P. bretschneideri ). These genes were randomly distributed on 17 chromosomes in each genome. Based on phylogenetics, the identified TIR1/AFB genes were divided into six groups. Their gene structure and motif pattern showed the intraspecific structural conservation as well as evolutionary patterns of Pyrus TIR1/AFBs. The expansion of this gene family in Pyrus is mainly caused by segmental duplication; however, a few genes showed tandem duplication. Moreover, positive and negative selection pressure equally directed the gene's duplication process. The GO and PPI analysis showed that Pyrus TIR1/AFB genes are associated with abiotic stress- and development-related signaling pathways. The promoter regions of Pyrus TIR1/AFB genes were enriched in hormone-, light-, development-, and stress-related cis elements. Furthermore, publicly available RNA-seq data analysis showed that DaTIR1/AFBs have varied levels of expression in various tissues and developmental stages, fruit hardening disease conditions, and drought stress conditions. This indicated that DaTIR1/AFB genes might play critical roles in response to biotic and abiotic stresses. The DaTIR1/AFBs have similar protein structures, which show that they are involved in the same function. Hence, this study will broaden our knowledge of the TIR1/AFB gene family in Pyrus , elucidating their contribution to conferring resistance against various environmental stresses, and will also provide valuable insights for future researchers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Yu, Gao, Fatima and Tahir Ul Qamar.)

Hypothermic liquid storage at 4-5 °C has emerged as a novel approach for preserving boar semen, offering innovative possibilities for semen preservation. However, this method also presents challenges, including cold shock and excessive reactive oxygen species (ROS) production. Therefore, reducing oxidative damage induced by low temperatures becomes essential while supplementing appropriate protectants. In this study, we investigated the efficacy of Bovine Serum Albumin (BSA) compared to Polyvinylpyrrolidone (PVP) and Skim Milk Powder (SMP) in maintaining boar sperm motility and progressive motility using computer-assisted sperm analysis (CASA). Among the tested concentrations, 4 g/L of BSA exhibited the best protective effect. Subsequently, we supplemented different concentrations of l-cysteine (LC) and N-acetyl-l-cysteine (NAC) as additives in the presence of BSA as a protectant. Our results demonstrated that 1 mmol/L of LC and 0.5 mmol/L of NAC exhibited superior protection of sperm quality compared to other concentrations. Furthermore, the 1 mmol/L LC and 0.5 mmol/L NAC groups showed significantly improved plasma membrane integrity and acrosome integrity compared to the control group. These groups also exhibited enhanced antioxidant capacity, evidenced by increased mitochondrial membrane potential (MMP), ATP production, total superoxide dismutase (T-SOD) activity, total antioxidant capacity (T-AOC), glutathione (GSH), glutathione peroxidase (GSH-PX), and GPX-4 levels. Additionally, they demonstrated decreased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, as well as reduced oxidized glutathione (GSSG) and glutathione reductase (GR) levels. Furthermore, LC and NAC treatment enhanced AMP-activated protein kinase (AMPK) phosphorylation. However, inhibiting AMPK using compound C did not inhibit the protective effects of LC and NAC on low-temperature preserved boar sperm. These findings suggest that 4 g/L BSA can serve as an effective protectant for hypothermic liquid storage of boar semen. Additionally, LC and NAC supplementation reduces oxidative damage by enhancing antioxidant capacity rather than through AMPK-mediated ATP supplementation. These results contribute to advancing the application of LC and NAC in hypothermic liquid storage of boar semen., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Our previous study showed that light-emitting diode modulation of the hypothalamic paraventricular nucleus (PVN), which is the control center of the sympathetic nervous system, might attenuate neuroinflammation in the PVN and prevent ventricular arrhythmias (VAs) after myocardial infarction (MI). Low-intensity focused ultrasound (LIFU) has deeper penetration than does light-emitting diode, while its effect on the PVN has not been reported., Objective: This study aimed to explore the effect of LIFU modulation of the PVN on the inducibility of post-MI VAs., Methods: Fifty-four Sprague-Dawley rats were randomly divided into acute control (n = 12, 22.22%), acute MI (AMI, n = 12, 22.22%), AMI + LIFU (n = 12, 22.22%), chronic control (n = 6, 11.11%), chronic MI (CMI, n = 6, 11.11%), and CMI + LIFU (n = 6, 11.11%) groups. MI was induced by left anterior artery ligation, and electrocardiographic recording for 0.5 hours after MI and programmed electrophysiological stimulation were used to test the vulnerability of VAs. Peripheral sympathetic neural activity was assessed by measuring left stellate ganglion neural activity. Finally, hearts and brains were extracted for Western blotting and histopathological analysis, respectively., Results: Compared with the AMI group, AMI-induced VAs (P < .05) and left stellate ganglion neural activity (P < .05) were significantly attenuated in the AMI + LIFU group. In addition, LIFU resulted in a significant reduction of microglial activation in the PVN and expression of inflammatory cytokines in the peri-ischemic myocardium. In the CMI + LIFU group, there was no obvious tissue damage in the brain., Conclusion: LIFU modulation of the PVN may prevent the incidence of post-MI VAs by attenuating MI-induced sympathetic neural activation and inflammatory response., Competing Interests: Disclosures The authors have no conflicts to disclose., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

The sol-gel process for fabricating electrochromic thin films is straightforward, offering advantages such as low cost and ease of compositional control. Herein we prepared GO-Bi-WO 3 films with improved electrochromic performance using a simple sol-gel spin-coating method. The sample shows a fast-switching time (1.8 s for coloring and 1.8 s for bleaching), large optical modulation (85% at 630 nm), excellent stability (86.4% retention after 10 200 cycles), and high coloration efficiency (65.9 cm 2 C -1 ). This work indicates the electrochromic performance of WO 3 -based films can be enhanced by incorporating GO, which provides an effective strategy for the rapid, safe, and efficient fabrication of electrochromic thin films.

Cardiac sympathetic overactivation is a critical driver in the progression of acute myocardial infarction (AMI). The left middle cervical ganglion (LMCG) is an important extracardiac sympathetic ganglion. However, the regulatory effects of LMCG on AMI have not yet been fully documented. In the present study, we detected that the LMCG was innervated by abundant sympathetic components and exerted an excitatory effect on the cardiac sympathetic nervous system in response to stimulation. In canine models of AMI, targeted ablation of LMCG reduced the sympathetic indexes of heart rate variability and serum norepinephrine, resulting in suppressed cardiac sympathetic activity. Moreover, LMCG ablation could improve ventricular electrophysiological stability, evidenced by the prolonged ventricular effective refractory period, elevated action potential duration, increased ventricular fibrillation threshold, and enhanced connexin43 expression, consequently showing antiarrhythmic effects. Additionally, compared with the control group, myocardial infarction size, circulating cardiac troponin I, and myocardial apoptosis were significantly reduced, accompanied by preserved cardiac function in canines subjected to LMCG ablation. Finally, we performed the left stellate ganglion (LSG) ablation and compared its effects with LMCG destruction. The results indicated that LMCG ablation prevented ventricular electrophysiological instability, cardiac sympathetic activation, and AMI-induced ventricular arrhythmias with similar efficiency as LSG denervation. In conclusion, this study demonstrated that LMCG ablation suppressed cardiac sympathetic activity, stabilized ventricular electrophysiological properties and mitigated cardiomyocyte death, resultantly preventing ischemia-induced ventricular arrhythmias, myocardial injury, and cardiac dysfunction. Neuromodulation therapy targeting LMCG represented a promising strategy for the treatment of AMI., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

This study explored 1-year follow-up of Parmaco-invasive strategy with half-dose recombinant human prourokinase (PHDP) in patients with acute ST-segment elevation myocardial infarction (STEMI). The follow-up endpoints were major adverse cardiovascular events (MACEs) occurring within 30 days and 1 year, as well as postoperative bleeding events. The study ultimately included 150 subjects, with 75 in the primary percutaneous coronary intervention (PPCI) group and 75 in the PHDP group. This study found that the PHDP group had a shorter FMC-reperfusion time (42.00 min vs 96.00 min, P < 0.001). During PCI, the PHDP group had a lower percutaneous transluminal coronary angioplasty (PTCA) ( P  = 0.021), intropin ( P  = 0.002) and tirofiban ( P  < 0.001) use. And the incidence of intraoperative arrhythmia, malignant arrhythmia, and slow flow/no-reflow was lower in the PHDP group ( P  < 0.001). At the 30-day follow-up, there was a significantly higher proportion of patients in the PPCI group who were readmitted due to unstable angina ( P  = 0.037). After 1 year of follow-up, there was no statistically significant difference in MACEs between the two groups ( P  = 0.500). The incidence of postoperative major bleeding, intracranial bleeding, and minor bleeding did not differ between the PHDP and PPCI groups ( P  > 0.05). The PHDP facilitates early treatment of infarct-related vessels, shortens FMC-reperfusion time, and does not increase the risk of MACEs., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Developing non-noble-metal electrocatalysts for hydrogen evolution reactions with high activity and stability is the key issue in green hydrogen generation based on electrolytic water splitting. It has been recognized that the stacking of large CoP particles limits the intrinsic activity of as-synthesized CoP catalyst for hydrogen evolution reaction. In the present study, N-Mo x C/CoP-0.5 with excellent electrocatalytic activity for hydrogen evolution reaction was prepared using N-Mo x C as decoration. A reasonable overpotential of 106 mV (at 10 mA cm -2 ) and a Tafel slope of 59 mV dec -1 in 1.0 M KOH solution was achieved with N-Mo x C/CoP-0.5 electrocatalyst, which exhibits superior activity even after working for 37 h. Uniformly distributed ultrafine nanoclusters of the N-Mo x C/CoP-0.5 hybrids could provide sufficient interfaces for enhanced charge transfer. The effective capacity of the hydrogen evolution reaction could be preserved in the complex, and the enlarged electrocatalytic surface area could be expected to offer more active sites for the reaction., (© 2023 IOP Publishing Ltd.)

Respiratory tract infections are associated with the most common diseases transmitted among people and remain a huge threat to global public health. Rapid and sensitive diagnosis of causative agents is critical for timely treatment and disease control. Here, we developed a novel method based on recombinase polymerase amplification (RPA) combined with CRISPR-Cas12a to detect three viral pathogens, including SARS-CoV-2, influenza A, and influenza B, which cause similar symptom complexes of flu cold in the respiratory tract. The detection method can be completed within 1 h, which is faster than other standard detection methods, and the limit of detection is approximately 10 2 copies/μL. Additionally, this detection system is highly specific and there is no cross-reactivity with other common respiratory tract pathogens. Based on this assay, we further developed a more simplified RPA/CRISPR-Cas12a system combined with lateral flow assay on a manual microfluidic chip, which can simultaneously detect these three viruses. This low-cost detection system is rapid and sensitive, which could be applied in the field and resource-limited areas without bulky and expensive instruments, providing powerful tools for the point-of-care diagnostic., (© 2023 Wiley Periodicals LLC.)

Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo . Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca 2+ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca 2+ -NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC., Competing Interests: The authors declare no conflicts of interest., (© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

In this paper, we propose a reflective terahertz (THz) Bessel metalens that utilizes polarization-insensitive sub-wavelength metal resonator-dielectric-metal structures. The Bessel metalens is configured with the superposition of hyperboloidal and conical phase profiles, resulting in a high-efficiency and long non-diffractive length Bessel beam. Our experimental results demonstrate that the proposed Bessel metalens has a focusing efficiency of 72.1% and a non-diffractive length of 239λ. This device has promising aspects in the fields of THz imaging systems and other miniaturized and integrated scenes that require non-diffractive Bessel beams.

Background: Electrical stimulation of the left stellate ganglion (LSG) can evoke ventricular arrhythmias (VAs) that originate from the right ventricular outflow tract (RVOT). The involvement of pulmonary artery innervation is unclear., Objectives: This study investigated the effects of selective pulmonary artery denervation (PADN) on blood pressure (BP), sympathetic activity, ventricular effective refractory period (ERP), and the incidence of VAs induced by LSG stimulation in canines., Methods: Radiofrequency ablation with basic anesthetic monitoring was used to induce PADN in canines. In Protocol 1 (n = 11), heart rate variability, serum norepinephrine and angiotensin-II levels, BP changes and ventricular ERP in response to LSG stimulation were measured before and after PADN. In Protocol 2 (n = 8), the incidence of VAs induced by LSG stimulation was calculated before and after PADN in a canine model of complete atrioventricular block. In addition, sympathetic nerves in the excised pulmonary arteries were immunohistochemically stained with tyrosine hydroxylase., Results: The low-frequency components of heart rate variability, serum norepinephrine and angiotensin-II levels were remarkably decreased post-PADN. Systolic BP elevation and RVOT ERP shortening induced by LSG stimulation were mitigated by PADN. The number of RVOT-premature ventricular contractions as well as RVOT tachycardia episodes and duration induced by LSG stimulation were significantly reduced after PADN. In addition, a large number of tyrosine hydroxylase-immunoreactive nerve fibers were located in the anterior wall of the pulmonary artery., Conclusions: PADN ameliorated RVOT ERP shortening, and RVOT-VAs induced by LSG stimulation by inhibiting cardiac sympathetic nerve activity., Competing Interests: Funding Support and Author Disclosures This work was supported by grants from the National Natural Science Foundation of China (82270402 and 82070425 to Dr Lu, 82000386 to Dr Deng), Natural Science Foundation of Hubei Province of China (2021CFA011 to Dr Lu), Health Commission of Hubei Province scientific research project (WJ2021Q039 to Dr He), Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University (ZNLH201907 to Dr Lu), Excellent Doctoral Program of Zhongnan Hospital of Wuhan University (ZNYB2019001 to Dr Deng), and Science and Technology Innovation cultivation fund of Zhongnan Hospital of Wuhan University (ZNPY2019005 to Dr Lu). All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Heterointerface engineering of NiFe (oxy)hydroxides is a prospective way of improving OER activity by the pre-catalysis of metal hydroxides accompanying the modulation of defects, but enhancement of the kinetics is controversial. Herein, in situ phase transformation of NiFe hydroxides was proposed and heterointerface engineering was optimized by sub-nano Au anchoring in simultaneously formed cation vacancies. Controllable size and concentrations of anchored sub-nano Au in the cation vacancies resulted in the modulation of the electronic structure at the heterointerface, and improved water oxidation activity was ascribed to the enhanced intrinsic activity and charge transfer rate. Here, Au/NiFe (oxy)hydroxide/CNTs with an Fe/Au molar ratio of 24 exhibited an overpotential of ∼236.3 mV at 10 mA cm -2 in 1.0 M KOH under simulated solar light irradiation, which is ∼19.8 mV lower than that without the consumption of solar energy. Spectroscopic studies reveal that the photo-responsive FeOOH in these hybrids and modulation of sub-nano Au anchoring in cation vacancies are favorable in improving solar energy conversion and suppressing photo-induced charge recombination.

Acute ischemic stroke (AIS) is the second leading cause of death worldwide. This study aims at assessing platelet morphology, ultrastructure and function changes of platelets in acute ischemic stroke (AIS) patients by the technique of Structured Illumination Microscopy (SIM). This assay collected platelet-rich plasma (PRP) from 11 AIS patients and 12 healthy controls. Each PRP sample was divided into 7 groups:1) rest group; 2) Thrombin-treated 5 min group; 3) Thrombin plus 2MeSAMP-treated 5 min group; 4) Thrombin plus Aspirin-treated 5 min group; 5) Thrombin-treated 1 h group; 6) Thrombin plus 2MeSAMP-treated 1 h group; 7) Thrombin plus Aspirin-treated 1 h group. SIM was applied to observe dense granules and α-granules morphology changes of platelet in AIS patients. FIJI was used to quantify the image data. We finally observed 1448 images of platelets within the 7 groups. In rest group, 7162 platelets were calculated platelet diameter, CD63 dots, average CD63-positive dots area, CD63-positive area per platelet, CD63-positive area Fov, VWF dots, average VWF-positive dots area, VWF-positive area per platelet and VWF-positive area Fov. ELISA was used to detect release of platelet factor 4 (PF4) of α-granules. The results showed that AIS patients had lower number and smaller area of platelet granules. Platelet α-granules of AIS patients concentrated to parenchymal-like fluorescent blocks in Thrombin-treated 1 h group. Antiplatelet drug treatment could reverse the concentration of platelets α-granules, and 2MeSAMP was more powerful than Aspirin in vitro. This study complemented detail information of platelet ultrastructure of AIS patients, provided a new perspective on the pathogenesis of AIS and the mechanism of antiplatelet drugs based on SIM and provided a reference for future related studies. SIM-based analysis of platelet ultrastructure may be useful for detecting antiplatelet drugs and AIS in the future., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

The intestinal epithelium barrier serves as a highly dynamic immunologic frontier in the defense against invading pathogenic bacteria and viruses. Hence, understanding of the complicated underlying relationship between enteric pathogens and the intestinal epithelium barrier is vital for developing strategies to improve the intestinal health of farm animals. To this end, Caco-2 cells were stimulated by 1 µg/ml lipopolysaccharide (LPS) for 24 h and 5 µg/ml polyinosinic-polycytidylic acid (ploy(I:C)) for 4 h to imitate bacterial and viral infection processes, respectively. The specific alterations in gene expression of Caco-2 cells after stimulation were characterized by transcriptome sequencing. Seventy differentially expressed genes (DEGs) were identified under LPS exposure, and 17 DEGs were observed under ploy(I:C) exposure. We found that most DEGs were specific, and only one common DEG SPAG7 was observed. Gene Ontology (GO) annotation analysis indicated that all DEGs identified in the different treatments were mainly derived from GO terms related to the maintenance of cellular homeostasis. Moreover, specific DEGs such as SLC39A10 , MT2A , and MT1E regulated by LPS treatment, while IFIT2 and RUNX2 mediated by ploy(I:C) treatment, which are derived from immune function modulation related GO terms, were confirmed by both transcriptome sequencing and qRT-PCR. In addition, both transcriptome sequencing and qRT-PCR results verified that LPS specifically down-regulated the DEGs INHBE and ARF6 , which are involved in inflammation responses related to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway including the TGF-beta signaling pathways and the Ras signaling pathway. Ploy(I:C) uniquely suppressed the DEGs GABARAP and LAMTOR3 , which participated in viral replication-associated pathways including autophagy and mTOR signaling pathway., Competing Interests: The authors declare there are no competing interests., (©2023 Qin et al.)

This paper presents a monolithically integrated aptasensor composed of a piezoresistive microcantilever array and an on-chip signal processing circuit. Twelve microcantilevers, each of them embedded with a piezoresistor, form three sensors in a Wheatstone bridge configuration. The on-chip signal processing circuit consists of a multiplexer, a chopper instrumentation amplifier, a low-pass filter, a sigma-delta analog-to-digital converter, and a serial peripheral interface. Both the microcantilever array and the on-chip signal processing circuit were fabricated on the single-crystalline silicon device layer of a silicon-on-insulator (SOI) wafer with partially depleted (PD) CMOS technology followed by three micromachining processes. The integrated microcantilever sensor makes full use of the high gauge factor of single-crystalline silicon to achieve low parasitic, latch-up, and leakage current in the PD-SOI CMOS. A measured deflection sensitivity of 0.98 × 10 - 6  nm -1 and an output voltage fluctuation of less than 1 μV were obtained for the integrated microcantilever. A maximum gain of 134.97 and an input offset current of only 0.623 nA were acquired for the on-chip signal processing circuit. By functionalizing the measurement microcantilevers with a biotin-avidin system method, human IgG, abrin, and staphylococcus enterotoxin B (SEB) were detected at a limit of detection (LOD) of 48 pg/mL. Moreover, multichannel detection of the three integrated microcantilever aptasensors was also verified by detecting SEB. All these experimental results indicate that the design and process of monolithically integrated microcantilevers can meet the requirements of high-sensitivity detection of biomolecules., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2023.)

Culex quinquefasciatus and Cx. tritaeniorhynchus are 2 dominant disease vectors in Neijiang City, Sichuan Province, China. Although there is evidence of confirmed resistance against insecticides in mosquito vectors, nothing is known about the existing insecticide resistance-conferring mutations in Cx. quinquefasciatus and Cx. tritaeniorhynchu in this region so far. In this study, the G119S mutation in the acetylcholinesterase (AChE) was detected in Cx. quinquefasciatus at a very low frequency (0.9%) with no resistant homozygotes being observed. Two resistance mutations in the voltage-gated sodium channel (VGSC) (L1014F and L1014S) were found in Cx. quinquefasciatus with frequencies of 88.7% and 8.3%, respectively. By contrast, the AChE F455W mutation was found to be fixed (with a frequency of 100%) in 3 of the 5 studied populations, with an overall frequency being 98.1%. In addition, 1 resistance-conferring VGSC mutation (L1014F) was detected with an overall frequency of 15.2% in Cx. tritaeniorhynchus. These results indicate that the well-recognized insecticide resistance-conferring mutations in both AChE and VGSC are present in the 2 Culex species in Neijiang. The contrasting patterns in the frequency of resistance alleles indicate that species-customized strategies of insecticide resistance management should be considered for the 2 species., (Copyright © 2023 by The American Mosquito Control Association, Inc.)

Transition metal oxides have drawn tremendous interest due to their unique physical and chemical properties. As one of the most promising electrochromic (EC) materials, tungsten trioxide (WO 3 ) has attracted great attention due to its exceptional EC characteristics. This review summarizes the background and general concept of EC devices, and key criteria for evaluation of WO 3 -based EC materials. Special focus is placed on preparation techniques and performance enhancement of WO 3 EC films. Specifically, four methods - nanostructuring, regulating crystallinity, fabricating hybrid films, and preparing multilayer composite structures - have been developed to enhance the EC performance of WO 3 films. Finally, we offer some important recommendations and perspectives on potential research directions for further study.

Chronic kidney disease (CKD) is a global disease that is harder to treat at a later stage. Therefore, early diagnosis and monitoring of CKD are crucial. T cell immunoglobulin and mucin domain molecule 3 (Tim-3) is a negative regulator of the T cell responses and it is involved in the immunomodulation of kidney disease. To date, only a small number of reports regarding serum soluble Tim-3 (sTim-3) in CKD are available. In the present study, the serum levels of sTim-3 in patients with CKD at different stages and the levels of sTim-3 in the early diagnosis and monitoring of CKD were analyzed. A highly sensitive time-resolved fluorescence immunoassay was performed to quantify sTim-3 levels in 318 patients with CKD and 114 healthy individuals. The serum levels of sTim-3 in patients with CKD (33.47±20.77 ng/ml) were significantly higher than those in the healthy individuals group (8.32±3.23 ng/ml; P<0.0001). As CKD progressed from stage G1 to G5, the serum sTim-3 level gradually increased (P<0.0001). A cut-off value of 13.63 ng/ml for the sTim-3 concentration was effective in diagnosing patients with CKD (area under the receiver operating characteristic curve, 0.9176; sensitivity, 79.87%; specificity, 96.49%). At this critical value, the positive detection rate of CKD in the early stages (G1 + G2), G3, G4 and G5 was 55.70, 77.78, 84.44 and 92.86%, respectively. In conclusion, the serum sTim-3 levels in patients with CKD were significantly higher than those in the healthy individuals group. As CKD progressed from G1 to G5, the serum sTim-3 concentration gradually increased, facilitating the monitoring of the progression of CKD. In addition, serum sTim-3 had an auxiliary effect that was useful in the early diagnosis of CKD. The positive detection rate of CKD in the early stages was 55.70%, which can assist other clinically common kidney disease indicators., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

Proteolytic enzymes and lipopeptides contain broad-spectrum antimicrobial activities, which have great potential for research and development. A microbial strain X49 obtained from protease screening plate showed antifungal activities against six fungi. Biochemical analysis, 16S rRNA sequencing, API identification system, and electron microscope analysis were carried out to identify the bacterium. Azocasein method was used to analyze the protease activity. Lipopeptides were extracted for antifungal analysis. The result indicated that strain X49 grew in the range of 10-50 ℃ and pH 4.0-9.0. Moreover, it survived in 10% NaCl, showing good halotolerance. Strain X49 was identified as Bacillus velezensis . Genomic analysis of B . velezensis X49 revealed eleven genes encoding serine protease. The ID 1&#95;894 belonging to S8 subtilisin family was 99% similar to the serine protease with known antifungal ability. On the other hand, thirty genes encoding non-ribosomal peptide synthetase involved in the lipopeptide biosynthesis, including surfactin, iturin, fengycin, bacitracin, and gramicidin, were identified. Part of the extracellular proteolytic activity remained under high temperature. After co-fermentation of B . velezensis X49 with Zingiber officinale Rosc., the antifungal activity of the lipopeptide extract from the co-fermentation was greatly improved. In conclusion, B . velezensis X49 showed clear inhibitory effect on both plant and human pathogens. The active substances co-fermented with Chinese herbs and microbes can be utilized for further drug development.

This study aimed to analyze the role of magnetic resonance imaging (MRI) data characteristics based on the deep learning algorithm in evaluating the treatment of diabetic foot (DF) with composite skin graft. In this study, 78 patients with DF were randomly rolled into the experimental group (composite skin graft) and control group (autologous skin graft) with 39 patients in each group. MRI scans were performed before and after treatment to compare the changes of experimental observation indicators such as healing time, recurrence rate, and scar score. The results showed that T1-weighted imaging (T1WI) of the scanning sequence was considerably increased in the experimental group after treatment. The signal intensity of fat-suppressed T2-weighted imaging (T2WI) and fat-suppressed T1WI enhancement sequences was considerably decreased ( P < 0.05). In addition, compared with the control group, the recurrence rate, healing time, and scar score in the experimental group were considerably decreased ( P < 0.05). The accuracy, specificity, and sensitivity of MRI imaging information in evaluating the therapeutic effect of DF patients were 85.2%, 89.75%, and 86.47%, respectively. According to the specificity and sensitivity, the subject operating characteristic curve was drawn, and the area under the curve was determined to be 0.838. In summary, MRI image data characteristics based on the deep learning algorithm can provide auxiliary reference information for the efficacy evaluation of compound skin transplantation for DF., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Chunlei Wang et al.)

Background: Viral hepatitis is a widespread and serious infectious disease, and most patients with liver cirrhosis and hepatocellular carcinoma are prone to viral infections. T cell immunoglobulin-and mucin-domain-containing molecule-3 (Tim-3) is an immune checkpoint molecule that negatively regulates T cell responses, playing an extremely important role in controlling infectious diseases. However, reports about the role of serum soluble Tim-3 (sTim-3) in hepatitis virus infection are limited. Therefore, this study explored changes in sTim-3 levels in patients infected with hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis E virus (HEV)., Methods: This study applied high-sensitivity time-resolved fluorescence immunoassay for the detection of sTim-3 levels. A total of 205 cases of viral hepatitis infection (68 cases of HBV infection, 60 cases of HCV infection, and 77 cases of HEV virus infection) and 88 healthy controls were quantitatively determined. The changes in serum sTim-3 level and its clinical value in hepatitis virus infection were analyzed., Results: Patients with HBV infection (14.00, 10.78-20.45 ng/mL), HCV infection (15.99, 11.83-27.00 ng/mL), or HEV infection (19.09, 10.85-33.93 ng/mL) had significantly higher sTim-3 levels than that in the healthy control group (7.69, 6.14-10.22 ng/mL, P < 0.0001). Patients with hepatitis and fibrosis infected with HBV (22.76, 12.82-37.53 ng/mL), HCV (33.06, 16.36-39.30 ng/mL), and HEV (28.90, 17.95-35.94 ng/mL) had significantly higher sTim-3 levels than patients with hepatitis without fibrosis (13.29, 7.75-17.28; 13.86, 11.48-18.64; 14.77, 9.79-29.79 ng/mL; P < 0.05)., Conclusion: sTim-3 level was elevated in patients infected with HBV, HCV, or HEV and gradually increased in patients with either hepatitis or hepatitis with hepatic fibrosis. It has a certain role in the evaluation of the course of a disease after hepatitis virus infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Yu, Lv, Dai, Wang, Zheng, Qin, Zhou, Wang, Pei, Fang and Huang.)

Objective: To explore the effects of nifedipine tablets combined with magnesium sulfate on blood coagulation indexes, oxidative stress and levels of NO and ET-1 in patients with Pregnancy-induced hypertension syndrome (PIH)., Methods: A total of 110 patients with hypertension during pregnancy were admitted to our hospital from January 2020 to January 2021. According to the random number table method, 110 patients were divided into the control group and the therapy group, with 55 cases in each group. The blood pressure levels (systolic and diastolic blood pressure), coagulation indexes (TT, PT, APTT, Fib), oxidative stress indexes (LPO, MDA, SOD), vascular endothelial function (ET-1, NO), clinical efficacy and adverse reactions of the two groups were compared., Results: After therapy, the systolic blood pressure and diastolic blood pressure of the two groups were significantly decreased, and the therapy group was significantly lower than the control group ( P < 0.05). After therapy, PT, TT, and APTT in two groups were significantly increased, and Fib was significantly decreased, and PT, TT, APTT in the therapy group were higher than those in the control group, and Fib was lower than that in the control group ( P < 0.05). After therapy, LPO and MDA in two groups were significantly decreased, and SOD was significantly increased, and LPO and MDA in the therapy group were lower than those in the control group, and SOD was higher than that in the control group ( P < 0.05). After therapy, ET-1 in two groups were significantly increased, and NO and ET-1/NO was significantly decreased, and ET-1 in the therapy group was higher than that in the control group, and NO and ET-1/NO were lower those in the control group ( P < 0.05). The total clinical effective rate of patients in the therapy group was 94.5%, and in the control group was 81.8%, the therapy group was significantly better than the control group ( P < 0.05). The total incidence of adverse reactions in the therapy group was 7.3%, and in the control group was 21.8%, the therapy group was significantly lower than the control group ( P < 0.05)., Conclusion: Nifedipine tablets combined with magnesium sulfate in the treatment of PIH can improve the blood coagulation function of patients, reduce oxidative stress damage, adjust the serum levels of ET-1 and NO, and improve the clinical efficacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yu and Zhou.)

Electroencephalogram (EEG) has been widely utilized in emotion recognition. Psychologists have found that emotions can be divided into conscious emotion and unconscious emotion. In this article, we explore to classify subliminal emotions (happiness and anger) with EEG signals elicited by subliminal face stimulation, that is to select appropriate features to classify subliminal emotions. First, multi-scale sample entropy (MSpEn), wavelet packet energy ( E i ), and wavelet packet entropy (WpEn) of EEG signals are extracted. Then, these features are fed into the decision tree and improved random forest, respectively. The classification accuracy with E i and WpEn is higher than MSpEn, which shows that E i and WpEn can be used as effective features to classify subliminal emotions. We compared the classification results of different features combined with the decision tree algorithm and the improved random forest algorithm. The experimental results indicate that the improved random forest algorithm attains the best classification accuracy for subliminal emotions. Finally, subliminal emotions and physiological proof of subliminal affective priming effect are discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shi, Zheng, Zhang, Yan, Li and Yu.)

Malignant eyelid tumors can invade adjacent structures and pose a threat to vision and even life. Early identification of malignant eyelid tumors is crucial to avoiding substantial morbidity and mortality. However, differentiating malignant eyelid tumors from benign ones can be challenging for primary care physicians and even some ophthalmologists. Here, based on 1,417 photographic images from 851 patients across three hospitals, we developed an artificial intelligence system using a faster region-based convolutional neural network and deep learning classification networks to automatically locate eyelid tumors and then distinguish between malignant and benign eyelid tumors. The system performed well in both internal and external test sets (AUCs ranged from 0.899 to 0.955). The performance of the system is comparable to that of a senior ophthalmologist, indicating that this system has the potential to be used at the screening stage for promoting the early detection and treatment of malignant eyelid tumors., (© 2022. The Author(s).)

The aim of this study was to establish a time-resolved fluorescent immunoassay (TRFIA) for the detection of serum Galectin-3 (Gal-3) and apply this method to evaluate the clinical significance of serum Gal-3 in predicting Idiopathic Membranous Nephropathy (IMN) progression. The Gal-3-TRFIA was established using the double antibody sandwich method, with the capture antibodies coated on a 96-well microplate and the detection antibodies chelated with Europium (III) (Eu 3+ ). Serum Gal-3 was detected in 81 patients with IMN and 123 healthy controls to further evaluate the value of the Gal-3 in staging of IMN. The sensitivity of the Gal-3-TRFIA assay was 0.85 ng/mL, and the detection range was 0.85-1000 ng/mL. The Gal-3 intra-batch and inter-batch coefficients of variation were 3.45% and 5.12%, respectively. The correlation coefficient (R) between the Gal-3-TRFIA assay and commercially available enzyme-linked immunosorbent assay kits was 0.83. The serum Gal-3 concentration was higher in patients with IMN (65.57 ± 55.90 ng/mL) compared to healthy controls (16.29 ± 9.91 ng/mL, P < 0.0001). In this study, a wide detection range Gal-3-TRFIA assay was developed using lanthanide (Eu 3+ ) chelates for the detection of Gal-3 concentrations in serum. Gal-3 concentration is elevated in patients with IMN., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

As one of the hallmarks of cancer, metabolic reprogramming leads to cancer progression, and targeting glycolytic enzymes could be useful strategies for cancer therapy. By screening a small molecule library consisting of 1320 FDA-approved drugs, we found that penfluridol, an antipsychotic drug used to treat schizophrenia, could inhibit glycolysis and induce apoptosis in esophageal squamous cell carcinoma (ESCC). Gene profiling and Ingenuity Pathway Analysis suggested the important role of AMPK in action mechanism of penfluridol. By using drug affinity responsive target stability (DARTS) technology and proteomics, we identified phosphofructokinase, liver type (PFKL), a key enzyme in glycolysis, as a direct target of penfluridol. Penfluridol could not exhibit its anticancer property in PFKL-deficient cancer cells, illustrating that PFKL is essential for the bioactivity of penfluridol. High PFKL expression is correlated with advanced stages and poor survival of ESCC patients, and silencing of PFKL significantly suppressed tumor growth. Mechanistically, direct binding of penfluridol and PFKL inhibits glucose consumption, lactate and ATP production, leads to nuclear translocation of FOXO3a and subsequent transcriptional activation of BIM in an AMPK-dependent manner. Taken together, PFKL is a potential prognostic biomarker and therapeutic target in ESCC, and penfluridol may be a new therapeutic option for management of this lethal disease., (© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Background: Gastric cancer (GC) has a poor prognosis and limited therapeutic options. As a new promising cancer therapeutic approach, chimeric antigen receptor (CAR)-T cells represent a potential GC treatment. We investigated the antitumor activity of CAR-T cells target-B7H3 in GC., Methods: In our study, expression of B7H3 was examined in GC tissues and explored the tumoricidal potential of B7H3-targeting CAR-T cells in GC. B7H3-directed CAR-T cells with a humanized antigen-recognizing domain was generated. The anti-tumor effects of this CAR-T cell were finally investigated in vitro and in vivo., Results: Our results show that B7H3-directed CAR-T cells efficiently killed GC tumor cells. In addition, we found that B7H3 is correlated with tumor cell stemness, and anti-B7H3 CAR-T can simultaneously target stem cell-like GC cells to improve the treatment outcome., Conclusions: Our study indicates that B7H3 is an attractive target for GC therapy, and B7H3 has high potential for clinical application., (© 2022. The Author(s).)

Multi-modal hashing learns compact binary hash codes by collaborating heterogeneous multi-modal features at both the model training and online retrieval stages to support large-scale multimedia retrieval. Previous multi-modal hashing methods mainly focus on supervised and unsupervised hashing. The performance of supervised hashing largely relies on the number of labeled data, which is practically expensive to obtain. Unsupervised hashing methods cannot effectively capture the semantic correlations of multi-modal data without any labels for supervision. In this paper, we propose an Efficient Semi-supervised Multi-modal Hashing with Importance Differentiation Regression (ESMH-IDR) model, which can alleviate the existing problems by learning from both labeled and unlabeled data. Specifically, in this paper, we develop an efficient semi-supervised multi-modal hash code learning module. It learns the hash codes for labeled data in an efficient asymmetric way, and simultaneously performs nonlinear regression using the same projection matrix as the labeled samples to preserve the intrinsic data structure of unlabeled data. Besides, different from existing methods, we propose an importance differentiation regression strategy to learn hash functions by specially considering the different importance of hash codes learned from the labeled and unlabeled samples. Finally, we develop an efficient discrete optimization method guaranteed with convergence to iteratively solve the hash optimization problem. Experiments on several public multimedia retrieval datasets demonstrate the superiority of our proposed method on both retrieval effectiveness and efficiency. Our source codes and testing datasets can be obtained at https://github.com/ChaoqunZheng/ESMH.

Objective: In this study, a novel, simple, and rapid immunoassay for the determination of gastrin-17 (G-17) in human serum was established by combining immunomagnetic beads with time-resolved fluorescence immunoassay (TRFIA)., Methods: Immunomagnetic beads were coated with anti-G-17 M01 antibody, anti-G-17 M02 antibody was labeled with Eu 3+ chelates. The concentration of G-17 in the serum was detected with the double-antibody sandwich method., Results: The limit of background(LOB), limit of detection (LOD), and limit of quantification (LOQ) were 0.09, 0.104, and 0.39 pmol/L, respectively. The detection range of G-17-TRFIA was 0.39-100 pmol/L. The average intra- and inter-assay coefficients of variation (CV) were 5.95%-9.07% and 6.09%-8.14%, respectively. The recoveries for the serum samples ranged from 94.70% to 100.95%. The specificity of our G-17-TRFIA was acceptable. The correlation coefficient between G-17-TRFIA and commercial G-17-ELISA methods was R 2  = 0.9092., Conclusions: A novel G-17-TRFIA detection method was successfully established to provide a reference for the early diagnosis of patients with atrophic gastritis in clinical research., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: The present study aimed to evaluate the clinical value of the combined detection of soluble T cell immunoglobulinand mucin domain molecule 3 (sTim-3) and pepsinogen (PG) in sera for gastric cancer (GC) diagnosis., Patients and Methods: The double antibody sandwich method was used to establish a highly sensitive time-resolved fluorescence immunoassay for the detection of sTim-3. Serum sTim-3, PGI, and PGII levels in 149 GC patients (123 first-diagnosis GC patients and 26 post-GC patients), 81 patients with benign gastric disease (BGD), and 73 healthy controls were quantitatively detected. The clinical diagnostic value of the combined detection of sTim-3 and PG in GC was analyzed., Results: Serum sTim-3 levels in GC (20.41 ± 9.55 ng/mL) and BGD (16.50 ± 9.76 ng/mL) patients were significantly higher (P < 0.001) than those in healthy controls (9.22 ± 3.40 ng/mL). Combined detection of sTim-3 and PGI/PGII (AUC: 0.9330, sensitivity: 86.44%, and specificity: 91.78%) showed a high diagnostic value for GC. When the level of PGI/PGII was less than 12.11 and that of sTim-3 was greater than 14.30 ng/mL, the positive rate of the control group was reduced to 0%, and the positive detection rate of GC was 54.47%. In addition, in post-operative patients, serum sTim-3 levels in the recurrence group (33.56 ± 4.91 ng/mL) were significantly higher than those in the no recurrence group (11.95 ± 5.16 ng/mL)., Conclusion: sTim-3 levels in BGD and GC sera were significantly higher than those in the control group sera. Additionally, sTim-3 serum levels can predict recurrence in post-operative patients. Compared with PG alone, the combined detection of serum PG and sTim-3 can significantly improve the detection sensitivity and specificity of BGD and GC., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Chen et al.)

The prognostic value of interleukin-6 (IL-6) in coronavirus disease 2019 (COVID-19) needs to be clarified. In this retrospective study, COVID-19 patients treated at Renmin Hospital of Wuhan University from January 7 to February 8, 2020 with measurements of serum IL-6 levels within 1 week after admission were included. Data regarding demographics, clinical characteristics, laboratory tests, complications, and outcomes were collected and analyzed. Sixty-six patients diagnosed with COVID-19 were included in this study (31 patients were females). They were divided into a normal group (serum IL-6 <10 pg/mL, n = 35) and an abnormal group (serum IL-6 <10 pg/mL, n = 31). Compared with the normal group, the incidence of critical cases (P <0.001), acute respiratory distress syndrome (ARDS) (P = 0.001), acute cardiac injury (P = 0.002), cardiac insufficiency (P = 0.039), mechanical ventilation rate (P = 0.002), and mortality (P = 0.021) was significantly increased in the abnormal group. Serum IL-6 concentration was an independent predictor of fatal outcome (P = 0.04). The optimal cutoff value of serum IL-6 concentration for predicting fatal outcomes was 26.09 pg/mL (P <0.001). In COVID-19, elevated serum IL-6 levels were associated with critical illness, use of mechanical ventilation, and complications, including heart injury and ARDS, and could predict a fatal outcome. Early detection of serum IL-6 levels after admission should be necessary in COVID-19 patients.

Acquisition of the direct electrochemical response of protein is the cornerstone for the development of the third generation of electrochemical biosensors. In this work, we developed a nanocluster-assisted protein-film voltammetry technique (NCA-PFV) which can achieve the acquisition of the electrochemical signal and maintain the activity without affecting of the protein's structure. With this strategy, a lipid bilayer membrane is used to immobilize the membrane protein so as to maintain its natural state. Copper nanoclusters with a size smaller than most proteins are then used to function at sub-protein scale and to mediate the electron hopping from the electroactive center of the electrode. As a model, the direct electrochemical signal of cyclooxygenase (COX) is successfully obtained, with a pair of well-defined redox peaks located at -0.39 mV and -0.31 mV, which characterize the heme center of the enzyme. Its catalytic activity towards the substrate arachidonic acid (AA) is also retained. The detection range for AA is 10-1000 μM and the detection limit is 2.4 μM. Electrochemical monitoring of the regulation of the catalytic activity by an inhibitor DuP-697 is also achieved. This work provides a powerful tool for the fabrication of enzyme-based electrochemical biosensors, and is also of great significance for promoting the development and application of next-generation electrochemical biosensors.

Background: The profiles of liver function abnormalities in COVID-19 patients need to be clarified., Methods: In this retrospective study, consecutive COVID-19 patients over 60 years old in Renmin Hospital of Wuhan University from January 1 to February 6 were included. Data of demographics, clinical characteristics, comorbidities, laboratory tests, medications and outcomes were collected and analysed. Sequential alterations of serum alanine aminotransferase (ALT) were monitored., Results: A total of 330 patients were included and classified into two groups with normal (n = 234) or elevated ALT (n = 96). There were fewer females (40.6% vs 54.7%, P = .020) and more critical cases (30.2% vs 19.2%, P = .026) in patients with elevated ALT compared with the normal group. Higher levels of bacterial infection indices (eg, white blood cell count, neutrophil count, C-reactive protein and procalcitonin) were observed in the elevated group. Spearman correlation showed that both ALT and AST levels were positively correlated with those indices of bacterial infection. No obvious effects of medications on ALT abnormalities were found. In patients with elevated ALT, most ALT elevations were mild and transient. 59.4% of the patients had ALT concentrations of 41-100 U/L, while only a few patients (5.2%) had high serum ALT concentrations above 300 U/L. ALT elevations occurred at 13 (10-17) days and recovered at 28 (18-35) days from disease onset. For most patients, the elevation of serum ALT levels occurred at 6-20 days after disease onset and reached their peak values within a similar time frame. The recovery of serum ALT levels to normal frequently occurred at 16-20 days or 31-35 days after disease onset., Conclusions: Liver function abnormalities were observed in 29.1% of elderly people COVID-19 patients, which were slightly and transient in most cases. Liver function abnormalities in COVID-19 may be correlated with bacterial infection., (© 2020 John Wiley & Sons Ltd.)

In this paper, a polyimide (PI)/Si/SiO 2 -based piezoresistive microcantilever biosensor was developed to achieve a trace level detection for aflatoxin B1. To take advantage of both the high piezoresistance coefficient of single-crystal silicon and the small spring constant of PI, the flexible piezoresistive microcantilever was designed using the buried oxide (BOX) layer of a silicon-on-insulator (SOI) wafer as a bottom passivation layer, the topmost single-crystal silicon layer as a piezoresistor layer, and a thin PI film as a top passivation layer. To obtain higher sensitivity and output voltage stability, four identical piezoresistors, two of which were located in the substrate and two integrated in the microcantilevers, were composed of a quarter-bridge configuration wheatstone bridge. The fabricated PI/Si/SiO 2 microcantilever showed good mechanical properties with a spring constant of 21.31 nN/μm and a deflection sensitivity of 3.54 × 10 -7 nm -1 . The microcantilever biosensor also showed a stable voltage output in the Phosphate Buffered Saline (PBS) buffer with a fluctuation less than 1 μV @ 3 V. By functionalizing anti-aflatoxin B1 on the sensing piezoresistive microcantilever with a biotin avidin system (BAS), a linear aflatoxin B1 detection concentration resulting from 1 ng/mL to 100 ng/mL was obtained, and the toxic molecule detection also showed good specificity. The experimental results indicate that the PI/Si/SiO 2 flexible piezoresistive microcantilever biosensor has excellent abilities in trace-level and specific detections of aflatoxin B1 and other biomolecules.

The present study aimed to review relevant, randomized, controlled trials in order to determine the effects of aspirin and heparin treatment on recurrent spontaneous abortion (RSA) in women with antiphospholipid syndrome (APS). Previous relevant studies were identified using PubMed, Cochrane, Embase, CNKI, VANFUN and VIP by retrieving appropriate key words. Additionally, key relevant sources in the literature were reviewed and articles published before May 2019 were included. The 22 selected studies included 1,515 patients in the treatment group and 1,531 patients in the control group. These previous studies showed that heparin and aspirin significantly improved live birth rate when compared with treatments using intravenous immunoglobulin, aspirin alone or aspirin combined with prednisone. Moreover, heparin and aspirin greatly increased the birth weight compared with placebo and improved vaginal delivery relative to intravenous immunoglobulin. The gestational age at birth was significantly higher in the heparin and aspirin group compared with the placebo group and the incidence of intrauterine growth restriction was lower in the heparin and aspirin group compared with the placebo group. Furthermore, heparin and aspirin markedly reduced the incidence of miscarriage compared with the aspirin group and the placebo group, and the incidence of pre-eclampsia was lower in the heparin and aspirin group than the placebo group. Thus, heparin and aspirin could be further examined for the treatment of RSA in women with APS., (Copyright: © Yu et al.)

We aimed to understand the evaluation of different Bowie-Dick test (B-D test) on the performance of pressure steam sterilization equipment in the case of simulated gas leakage, and we selected a pulsating vacuum steam sterilizer to set 4 different gas leakage levels: 1.1, 1.3, 1.5, and 1.7 mbar/min during the B-D test phase. In terms of methods, 4 different brands of B-D test kits (devices) were tested at 4 different leakage rates, and a total of 48 experiments were conducted. The results from univariate analysis revealed that there are statistically significant differences in the judgment of test results among different personnel and brands. The results from multivariate logistic regression analysis displayed that the difference between different personnel was statistically significant (χ = 45.34, P < .001); the difference between different products was statistically significant (χ = 129.37, P < .001); and there was no statistically significant difference between different degree of leakage (χ = 6.99, P > .05). Result judgments of brand 1 and brand 2 are susceptible to subjective factors. The judgment of brand 3 is intuitive and consistent with the evaluation result of brand 4. In conclusion, the order of capacity to evaluate air leakage from best to worst is brand 4→brand 3→brand 1→brand 2.

This paper introduces a piezoresistive microcantilever with a low spring constant. The microcantilever was fabricated with titanium (Ti) as the piezoresistor, a low spring constant polyimide (PI) layer, and a thin silicon oxide (SiO 2 ) layer as the top and bottom passive layers, respectively. Excellent mechanical performances with the spring constant of 0.02128 N/m and the deflection sensitivity (∆V/V)/∆z of 1.03 × 10 -7 nm -1 were obtained. The output voltage fluctuation of a Wheatstone bridge, which consists of four piezoresistive microcantilevers, is less than 3 μV@3 V in a phosphate buffered saline (PBS) environment. A microcantilever aptasensor was then developed through functionalizing the microcantilevers with a ricin aptamer probe, and detections on ricin with concentrations of 10, 20, 50 and 100 ng/mL were successfully realized. A good specificity was also confirmed by using bovine serum albumin (BSA) as a blank control. The experiment results show that the Ti and PI-based microcantilever has great prospects for ultrasensitive biochemical molecule detections with high reliability and specificity.

Objective: To investigate the characteristics and prognostic factors in the elderly patients with COVID-19., Methods: Consecutive cases over 60 years old with COVID-19 in Renmin Hospital of Wuhan University from Jan 1 to Feb 6, 2020 were included. The primary outcomes were death and survival till March 5. Data of demographics, clinical features, comorbidities, laboratory tests and complications were collected and compared for different outcomes. Cox regression was performed for prognostic factors., Results: 339 patients with COVID-19 (aged 71±8 years,173 females (51%)) were enrolled, including 80 (23.6%) critical, 159 severe (46.9%) and 100 moderate (29.5%) cases. Common comorbidities were hypertension (40.8%), diabetes (16.0%) and cardiovascular disease (15.7%). Common symptoms included fever (92.0%), cough (53.0%), dyspnea (40.8%) and fatigue (39.9%). Lymphocytopenia was a common laboratory finding (63.2%). Common complications included bacterial infection (42.8%), liver enzyme abnormalities (28.7%) and acute respiratory distress syndrome (21.0%). Till Mar 5, 2020, 91 cases were discharged (26.8%), 183 cases stayed in hospital (54.0%) and 65 cases (19.2%) were dead. Shorter length of stay was found for the dead compared with the survivors (5 (3-8) vs. 28 (26-29), P < 0.001). Symptoms of dyspnea (HR 2.35, P = 0.001), comorbidities including cardiovascular disease (HR 1.86, P = 0.031) and chronic obstructive pulmonary disease (HR 2.24, P = 0.023), and acute respiratory distress syndrome (HR 29.33, P < 0.001) were strong predictors of death. And a high level of lymphocytes was predictive of better outcome (HR 0.10, P < 0.001)., Conclusions: High proportion of severe to critical cases and high fatality rate were observed in the elderly COVID-19 patients. Rapid disease progress was noted in the dead with a median survival time of 5 days after admission. Dyspnea, lymphocytopenia, comorbidities including cardiovascular disease and chronic obstructive pulmonary disease, and acute respiratory distress syndrome were predictive of poor outcome. Close monitoring and timely treatment should be performed for the elderly patients at high risk., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interests., (Copyright © 2020. Published by Elsevier Ltd.)

We report a tunable terahertz (THz) metamaterial absorber (MA) actuated by thermomechanical bimaterial microcantilevers. The THz MA, which is suspended on a silicon substrate by the bimaterial microcantilevers, is a sandwich structure with a bottom Al ground plane, middle air and SiN x dielectric layers, and a top Al rotationally symmetric open split ring resonator. Upon application of a current, a Ti heating resistor integrated on the SiN x dielectric layer induces the bimaterial microcantilevers to bend, causing the air layer thickness to change, modulating the absorption of the THz MA. The tunable THz MA exhibited a relative modulation depth of absorption of 28.1% at 0.69 THz and a thermomechanical sensitivity of 0.12°/K. This tunable THz MA has potential applications in filtering, modulation, control, and THz imaging.

Scope: Vegetarian diets confer health benefits to many cardiometabolic diseases, although whether and how gut microbiota in vegetarians contributes to host metabolism remains unclear. Thus, the aim is to explore the possible links between the gut microbiota and circulating gut microbiota-host co-metabolites among vegetarians and omnivores., Methods and Results: Fecal and serum samples from 36 adults following a vegan, lacto-ovo vegetarian, or omnivorous diet are collected. A 16S rRNA gene, metagenome, metatranscriptome, and metabolome integrated multi-omics approach is adopted to profile fecal microbial composition and functionality and circulating gut microbiota-host co-metabolites. 16S rRNA gene and metagenomic sequencing suggest a significant difference in gut microbial composition between the two vegetarian groups and the omnivorous group at the family, genus, and species level. Metabolomic analysis reveals that circulating branched-chain amino acids (BCAAs)-valine, leucine, and isoleucine-are significantly lower in the two vegetarian groups than those in the omnivorous group. In line with the lower concentrations of BCAAs, metatranscriptomic analysis shows that the gut microbial pathway for the degradation of BCAAs is significantly upregulated among vegetarians compared with the omnivores., Conclusions: The results indicate that gut microbiota plays an important role in the modulation of circulating BCAAs among vegetarians., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: Our recent study found that selective ablation of the distal part of the ligament of Marshall (LOM LSPV ) could suppress ventricular arrhythmias (VAs) during acute myocardial infarction (AMI). This study was to investigate the possible underlying mechanisms., Methods: Dogs were randomly divided into the sham-operated group (SO; n = 6), AMI group (AMI; n = 8) and the group undergoing LOM LSPV ablation ahead of AMI (LOMD+AMI; n = 8). Incidence of VAs, serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD), expression of connexin (Cx43), Bcl-2, Bax, caspase-3, tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), and high mobility group box (HMGB)1 were compared. Anatomic and immunostaining examinations of LOM LSPV were performed., Results: Compared with the AMI group, incidence of VAs was reduced in the LOMD+AMI group. Compared with the SO group, Cx43, SOD, and Bcl-2 were decreased, MDA, Bax, caspase-3, TNF-α, IL-6, and HMGB1 were increased in the MI group, and all the alterations were significantly restrained in the LOMD+AMI group. A visual nerve fiber communication between the left stellate ganglion (LSG) and LOM and abundant sympathetic nerve bundles distribution in LOM LSPV were revealed., Conclusions: LOM LSPV ablation could suppress VAs during AMI. The possible mechanism may be associated with disconnection of the sympathetic conduit from LSG to the ventricles. Preservation of Cx43, inhibition of cardiac oxidative stress, apoptosis, and inflammation may be involved., (© 2018 Wiley Periodicals, Inc.)

Background: Atrial ganglionated plexus (GP) ablation was proved to have therapeutic effects on vasovagal syncope. The study aimed to investigate whether selective ablation of only right anterior GP (ARGP) and right inferior GP (IRGP) was effective in a canine model of vasovagal syncope., Methods: Seventeen mongrel dogs were divided into control (N = 10) and ablation group (N = 7). Bilateral thoracotomy was performed at the fourth intercostal space and ARGP and IRGP were ablated in the ablation group. A bolus of veratridine (15 ug/kg) was injected into the left atrium to induce vasovagal reflex. Surface electrocardiogram and blood pressure (BP) were continuously monitored. Heart rate (HR) variability was calculated to represent cardiac autonomic tone., Results: Veratridine injection induced vasovagal reflex in all dogs. HR decreased from 149 ± 17 to 89 ± 33 beats/min (P < 0.001) in the control group, while in the ablation group HR decreased from 141 ± 35 to 125 ± 34 beats/min (P = 0.032). The postveratridine HR in the ablation group was significantly higher than that in the control group (P = 0.045). A significantly less intense HR decrease was observed in the ablation group compared with control (-17 ± 16 vs -61 ± 34 beats/min, P = 0.006). Significant BP decreases were induced in both the groups (all P < 0.01), while no evident differences in postveratridine BP and the extent of BP decreases were found between the groups. HR variability revealed significant decrease in cardiac vagal tone after ablation [high-frequency power, 0.50 (0.17-1.05) vs 6.28 (0.68-8.99) ms 2 , P = 0.005]., Conclusions: Selective ablation of ARGP + IRGP weakened cardiac parasympathetic control and significantly attenuated the cardioinhibitory response in an animal model of vasovagal reflex. This ablation strategy might be effective for vasovagal syncope with evident cardioinhibitory response., (© 2018 Wiley Periodicals, Inc.)

In this paper, we demonstrate an ultra-broadband terahertz (THz) bi-metasurfaces absorber composed of two stacking metasurfaces backed by a metallic ground plane. The bottom metasurface consists of four multiplexed cross resonators with different geometries on a thin parylene layer, achieving a bandwidth of 3.80 THz with the absorption higher than 50% at high frequency. Meanwhile, the top metasurface, including two multiplexed cross resonators with different sizes on a relatively thicker parylene layer, provides a low frequency absorption band with an additional Salisbury screen absorption peak that connects the two absorption bands of the two metasurfaces, therefore enabling an ultra-broadband absorption. The experimental absorption spectrum of the bi-metasurfaces shows a bandwidth of 4.46 THz while the absorption exceeding 50% and a full width at half maxima (FWHM) of 97.7%. The ultra-broadband absorber will be a promising candidate for THz broadband detection.

Introduction: Cardiac sympathetic activation facilitates atrial electrical remodeling during atrial fibrillation (AF). Selective ablation of the distal part of the ligament of Marshall (LOM LSPV ) could decrease cardiac sympathetic innervation. This study aimed to investigate the effects of LOM LSPV ablation on atrial electrical remodeling in a short-term rapid atrial pacing (RAP) model., Methods: In 16 anesthetized dogs, 6 hours of RAP (20 Hz, 2 × threshold) was delivered before LOM LSPV ablation (group 1, N  =  8) or after (group 2, N  =  8). Heart rate variability (HRV), serum norepinephrine (NE), atrial electrophysiological indices were analyzed. Six times of burst pacing (20 Hz, 2 × threshold, lasting for 5 seconds, were performed to induce AF, the number of episodes and the duration of AF were compared., Results: LOM LSPV ablation decreased sympathetic indices of HRV and serum NE. Atrial effective refractory period (ERP) was shortened during RAP in both groups with higher reduction degrees in group 1. In group 1, the shortening of atrial ERP, elevating of ERP dispersion and sum of window of vulnerability (ΣWOV), facilitating of AF induced by RAP were subsequently reversed by LOM LSPV ablation. In group 2, LOM LSPV ablation prolonged atrial ERP, decreased ΣWOV, eliminated AF induction. The subsequent RAP failed to alter these indices. Histological studies showed abundant sympathetic nerve fibers in LOM LSPV ., Conclusion: LOM LSPV ablation could inhibit atrial electrical remodeling during short-term RAP by reducing the cardiac sympathetic activity. LOM LSPV may be a potential target in AF ablation, especially in patients with highly cardiac sympathetic activation or atrial electrical remodeling., (© 2018 Wiley Periodicals, Inc.)

Cardiac sympathetic tone overdrive is a key mechanism of arrhythmia. Cardiac sympathetic nerves denervation, such as LSG ablation or renal sympathetic denervation, suppressed both the prevalence of VAs and the incidence of SCD. Accumulating evidence demonstrates the ligament of Marshall (LOM) is a key component of the sympathetic conduit between the left stellate ganglion (LSG) and the ventricles. The present study aimed to investigate the roles of the distal segment of LOM (LOMLSPV) denervation in ischemia and reperfusion (IR)-induced VAs, and compared that LSG denervation. Thirty-three canines were randomly divided into group 1 (IR group, n = 11), group 2 (LOMLSPV Denervation + IR, n = 9), and group 3 (LSG Denervation + IR, n = 13). Hematoxylin-Eosin (HE) and Immunohistochemistry staining revealed that LOMLSPV contained bundles of sympathetic but not parasympathetic nerves. IR increased the cardiac sympathetic tone [serum concentrations of noradrenaline (NE) and epinephrine (E)] and induced the prevalence of VAs [ventricular premature beat (VPB), salvo of VPB, ventricular tachycardia (VT), VT duration (VTD) and ventricular fibrillation (VF)]. Both LOMLSPV denervation and LSG denervation could reduce the cardiac sympathetic tone in Baseline (BS) [heart rate variability (HRV)]. Compared with group 1, LOMLSPV denervation and LSG denervation similarly reduced sympathetic tone [NE (1.39±0.068 ng/ml in group 2, 1.29±0.081 ng/ml in group 3 vs 2.32±0.17 ng/ml in group 1, P<0.05) and E (114.64±9.22 pg/ml in group 2, 112.60±9.69 pg/ml in group 3 vs 166.18±15.78 pg/ml in group 1, P<0.05),] and VAs [VT (0±3.00 in group 2, 0±1.75 in group 3 vs 8.00±11.00 in group 1, P<0.05) and VTD (0 ± 4 s in group 2, 0±0.88s in group 3 vs 10.0 ± 22.00s in group 1, P<0.05)] after 2h reperfusion. These findings indicated LOMLSPV denervation reduced the prevalence of VT by suppressing SNS activity. These effects are comparable to those of LSG denervation. In myocardial IR, the anti-arrhythmic effects of LOMLSPV Denervation may be related to the inhibition of the expression of NE and E., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Individuals predisposed to vasovagal syncope may have different autonomic nervous system control mechanisms from those without predisposition to vasovagal events. To test this hypothesis, we investigated different sympathetic responses in a canine model of vasovagal syncope., Methods: Left thoracotomy was performed on 20 mongrel dogs. The heart was exposed and a bolus of veratridine (15 μg/kg), a neurotoxin which prevents the inactivation of sodium ion channels, was injected into the left atrium to induce a Bezold-Jarisch reflex-mediated vasovagal event, characterized by bradycardia, decreased inotropism, and hypotension. Electrocardiogram and blood pressure were continuously monitored. Neural activity was recorded from the left stellate ganglion. Plasma norepinephrine and acetylcholine levels were measured 30 s before and 30 s after veratridine injection., Results: Veratridine resulted in rapid decreases in heart rate and blood pressure in all dogs, accompanied by increases in both norepinephrine and acetylcholine. Two types of neural activity (high-amplitude spike discharge activity and low-amplitude burst discharge activity) were recorded from the left stellate ganglion. Veratridine induced high-frequency spike discharge activity in some dogs (Group A), whereas spike discharge activity was scarce and relatively unresponsive to veratridine in the remaining dogs (Group B). Dogs in Group A had higher plasma norepinephrine levels (111.63 ± 15.1 vs. 48.11 ± 33.81 ng/l, p = 0.002) and less intense drops in heart rate (- 37 ± 24 vs. - 84 ± 28 bpm, p = 0.001) and blood pressure (systolic blood pressure, - 18 ± 15 vs. - 37 ± 13 mmHg, p = 0.009; diastolic blood pressure, - 26 ± 13 vs. - 45 ± 13 mmHg, p = 0.005) compared to dogs in Group B. Similarly, heart rate post-veratridine was higher (102 ± 23 vs. 69 ± 22 bpm, p = 0.004), the veratridine-induced longest RR interval was shorter (0.7 [0.5-0.8] vs. 1.2 [1.1-3.5] s, p < 0.001) and the diastolic and mean arterial pressures post-veratridine were higher (all p < 0.05) in dogs in Group A compared to those in Group B., Conclusions: Distinct sympathetic activation as represented by left stellate ganglion high-frequency spike discharge activity protected against bradycardia and hypotension in a canine model of vasovagal syncope. Our findings may have therapeutic implications.

Background: Sympathetic denervation exerts protective effects against ventricular arrhythmias (VAs) induced by acute myocardial infarction. The results of a previous study indicated that the distal part of the ligament of Marshall (LOM LSPV ) might be a sympathetic conduit between the left stellate ganglion (LSG) and the ventricles. The present study was designed to compare the effects between LSG and LOM LSPV ablation on ischemia-induced VAs., Methods: Twenty-nine dogs were randomly divided into sham ablation group (group 1, n=9), LOM LSPV ablation group (group 2, n=10), and LSG ablation group (group 3, n=10). Ablation was performed before occlusion of the left anterior coronary artery. Changes in the heart rate variability, serum norepinephrine, ventricular effective refractory period, and blood pressure induced by LSG stimulation were observed, and the occurrence of VAs was recorded. Immunostaining examinations of LOM LSPV were performed in dogs without ablation., Results: In group 2, LOM LSPV ablation evidently attenuated blood pressure elevation induced by LSG stimulation. Both LOM LSPV ablation and LSG ablation similarly prolonged ventricular effective refractory period and reduced the concentration of serum norepinephrine, the sympathetic index of heart rate variability, and the incidence of VAs compared with sham ablation. Abundant sympathetic nerve fibers were observed in LOM LSPV ., Conclusions: LOM LSPV ablation prevented acute myocardial infarction-induced VAs with the same efficiency as LSG ablation, potentially by blocking the sympathetic pathway from the LSG to the heart., (© 2018 American Heart Association, Inc.)