SMYD1 modulates the proliferation of multipotent cardiac progenitor cells derived from human pluripotent stem cells during myocardial differentiation through GSK3ß/ß-catenin&ERK signaling.

BACKGROUND: The histone-lysine N-methyltransferase SMYD1, which is specific to striated muscle, plays a crucial role in regulating early heart development. Its deficiency has been linked to the occurrence of congenital heart disease. Nevertheless, the precise mechanism by which SMYD1 deficiency contributes to congenital heart disease remains unclear. METHODS: We established a SMYD1 knockout pluripotent stem cell line and a doxycycline-inducible SMYD1 expression pluripotent stem cell line to investigate the functions of SMYD1 utilizing an in vitro-directed myocardial differentiation model. RESULTS: Cardiomyocytes lacking SMYD1 displayed drastically diminished differentiation efficiency, concomitant with heightened proliferation capacity of cardiac progenitor cells during the early cardiac differentiation stage. These cellular phenotypes were confirmed through experiments inducing the re-expression of SMYD1. Transcriptome sequencing and small molecule inhibitor intervention suggested that the GSK3ß/ß-catenin&ERK signaling pathway was involved in the proliferation of cardiac progenitor cells. Chromatin immunoprecipitation demonstrated that SMYD1 acted as a transcriptional activator of GSK3ß through histone H3 lysine 4 trimethylation. Additionally, dual-luciferase analyses indicated that SMYD1 could interact with the promoter region of GSK3ß, thereby augmenting its transcriptional activity. Moreover, administering insulin and Insulin-like growth factor 1 can enhance the efficacy of myocardial differentiation in SMYD1 knockout cells. CONCLUSIONS: Our research indicated that the participation of SMYD1 in the GSK3ß/ß-catenin&ERK signaling cascade modulated the proliferation of cardiac progenitor cells during myocardial differentiation. This process was partly reliant on the transcription of GSK3ß. Our research provided a novel insight into the genetic modification effect of SMYD1 during early myocardial differentiation. The findings were essential to the molecular mechanism and potential interventions for congenital heart disease.

In vivo proximity proteomics uncovers palmdelphin (PALMD) as a Z-disc-associated mitigator of isoproterenol-induced cardiac injury.

Z-discs are core ultrastructural organizers of cardiomyocytes that modulate many facets of cardiac pathogenesis. Yet a comprehensive proteomic atlas of Z-disc-associated components remain incomplete. Here, we established an adeno-associated virus (AAV)-delivered, cardiomyocyte-specific, proximity-labeling approach to characterize the Z-disc proteome in vivo. We found palmdelphin (PALMD) as a novel Z-disc-associated protein in both adult murine cardiomyocytes and human pluripotent stem cell-derived cardiomyocytes. Germline and cardiomyocyte-specific Palmd knockout mice were grossly normal at baseline but exhibited compromised cardiac hypertrophy and aggravated cardiac injury upon long-term isoproterenol treatment. By contrast, cardiomyocyte-specific PALMD overexpression was sufficient to mitigate isoproterenol-induced cardiac injury. PALMD ablation perturbed the transverse tubule (T-tubule)-sarcoplasmic reticulum (SR) ultrastructures, which formed the Z-disc-associated junctional membrane complex (JMC) essential for calcium handling and cardiac function. These phenotypes were associated with the reduction of nexilin (NEXN), a crucial Z-disc-associated protein that is essential for both Z-disc and JMC structures and functions. PALMD interacted with NEXN and enhanced its protein stability while the Nexn mRNA level was not affected. AAV-based NEXN addback rescued the exacerbated cardiac injury in isoproterenol-treated PALMD-depleted mice. Together, this study discovered PALMD as a potential target for myocardial protection and highlighted in vivo proximity proteomics as a powerful approach to nominate novel players regulating cardiac pathogenesis.

Simultaneous determination of four fungicide residues in figs using liquid chromatography tandem mass spectrometry.

Dissipative behavior and final residue levels of difenoconazole, prochloraz, propiconazole, and pyraclostrobin in figs were investigated using field trials and laboratory assays. A three-factor, three-level orthogonal test was designed to optimize the pretreatment conditions of the method. A method was established using high-performance liquid chromatography tandem mass spectrometry for the determination of difenoconazole, prochloraz, propiconazole, and pyraclostrobin residues in figs. The limit of quantification for all four targets in figs was 0.002 mg/kg. Difenoconazole, prochloraz, propiconazole, and pyraclostrobin are readily digestible pesticides in figs with half-lives of 6.4, 6.2, 4.8, and 7.9 days, respectively. Residues of difenoconazole, prochloraz, propiconazole, and pyraclostrobin in figs were below the European Union established residue levels of 0.1, 0.03, 0.01, and 0.02 mg/kg, respectively, at day 7 after application. Pyraclostrobin, propiconazole, difenoconazole, and prochloraz were applied twice at doses of 75, 125, 150, and 200 mg a.i./kg at 7-day intervals, and the residues of the four fungicides in figs were acceptable 7 days after the last application. Therefore, the safety interval can be set at 7 days for 70% difenoconazole-prochloraz wettable powder and 40% pyraclostrobin-propiconazole aqueous emulsion according to the protocol.

Crispr-Based Editing of Human Pluripotent Stem Cells for Disease Modeling.

The CRISPR system, as an effective genome editing technology, has been extensively utilized for the construction of disease models in human pluripotent stem cells. Establishment of a gene mutant or knockout stem cell line typically relies on Cas nuclease-generated double-stranded DNA breaks and exogenous templates, which can produce uncontrollable editing byproducts and toxicity. The recently developed adenine base editors (ABE) have greatly facilitated related research by introducing A/T > G/C mutations in the coding regions or splitting sites (AG-GT) of genes, enabling mutant gene knock-in or knock-out without introducing DNA breaks. In this study, we edit the AG bases in exons anterior to achieve gene knockout via the ABE8e-SpRY, which recognizes most expanded protospacer adjacent motif to target the genome. Except for gene-knockout, ABE8e-SpRY can also efficiently establish disease-related A/T-to-G/C variation cell lines by targeting coding sequences. The method we generated is simple and time-saving, and it only takes two weeks to obtain the desired cell line. This protocol provides operating instructions step-by-step for constructing knockout and point mutation cell lines.

Demonstration of bound states in the continuum in substrate integrated waveguides.

Substrate integrated waveguides (SIWs) components play a crucial role in microwave devices fabricated by printed circuit board (PCB) technology. Bound states in the continuum (BICs) have high-quality factors that approach infinity. So far, there is little research on BICs in SIWs. Therefore, we studied a symmetry-protected BIC generated by the coupling between SIW and SIW resonators to fill this gap. Using the revised coupled mode theory (CMT), we explored the mechanism of resonance generation in this system. In addition, the effect of the geometrical parameters on the resonance is also investigated and higher Q3dB factors are obtained. The findings offer new insights into the design of BIC devices by traditional PCB technology, thus contributing to future applications in the integrated circuits field.

Anti-thymic stromal lymphopoietin monoclonal antibody in patients with chronic rhinosinusitis with nasal polyps (DUBHE): Rationale and design of a multicenter, randomized, double-blind, placebo-controlled study.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) has a complex pathogenesis and is difficult to treat, which brings a huge economic burden to society. Despite all the progress in the treatment of CRSwNP, some patients with CRSwNP still experience recurrence. Therefore, there is an urgent need to develop novel drugs and treatments for CRSwNP. Thymic stromal lymphopoietin (TSLP) is produced by epithelial cells and mediates type 2 and nontype 2 inflammation through various downstream cellular immune and inflammatory pathways. Anti-TSLP treatment with tezepelumab has been proven to be effective in treating patients with uncontrolled asthma, regardless of their peripheral blood eosinophil levels being low or high. However, there is no relevant research on the usage of anti-TSLP monoclonal antibodies for the treatment of uncontrolled CRSwNP. Objective: This is the first phase Ib/IIa study for subjects with uncontrolled CRSwNP, aiming to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy of multiple ascending doses (MAD) of anti-TSLP monoclonal antibody. Methods: The DUBHE is a multicenter, randomized, double-blind, placebo-controlled, phase Ib/IIa clinical study. The study will be composed of 3 periods: a screening/run-in period of 4 weeks, a treatment period of 52 weeks (16 weeks of double-blind treatment period +36 weeks of open-label treatment period), and a safety follow-up period of 12 weeks. No more than 113 subjects with uncontrolled CRSwNP will be divided into 4 groups to receive different doses of CM326 or placebo treatments (55 mg every two weeks [Q2W] group, 110 mg Q2W group, 220 mg Q2W group, and 220 mg every four weeks [Q4W] group). Enrolled patients will be stratified by tissue eosinophil count (TEC). Results: The safety of the monoclonal antibody that targets TSLP in uncontrolled CRSwNP and its preliminary efficacy at 16 weeks of treatment. Conclusion: In this study, for the first time, the safety and preliminary efficacy of MAD of CM326 will be verified. The efficacy of CM326 in patients with eosinophilic CRSwNP (TEC ≥55/high power field [HPF]), as well as noneosinophilic CRSwNP (TEC <55/HPF) will be testified. Trial registration: NCT05324137.

Tunable C-H functionalization and dearomatization enabled by an organic photocatalyst.

C-H functionalization and dearomatization constitute fundamental transformations of aromatic compounds, which find wide applications in various research areas. However, achieving both transformations from the same substrates with a single catalyst by operating a distinct mechanism remains challenging. Here, we report a photocatalytic strategy to modulate the reaction pathways that can be directed toward either C-H functionalization or dearomatization under redox-neutral or net-reductive conditions, respectively. Two sets of indoles and indolines bearing tertiary alcohols are divergently furnished with good yields and high selectivity. The key to success is the introduction of isoazatruxene ITN-2 as a novel photocatalyst (PC), which outperforms the commonly used PCs. The ready synthesis and high modulability of isoazatruxene type PCs indicate their great application potential.

The value of sequential application of hydrogen peroxide, povidone-iodine and physiological saline in reducing postoperative infections after total knee arthroplasty: A prospective, randomized, controlled study.

BACKGROUND: Currently, in the field of total joint arthroplasty (TJA), there are no studies that have demonstrated the value of the sequential application of hydrogen peroxide, povidone-iodine, and physiological saline during the surgical procedure in decreasing postoperative infections in total knee arthroplasty (TKA), and in decreasing the incidence of periprosthetic joint infections (PJI) in particular. This study aimed to assess the efficacy of the sequential application of hydrogen peroxide, povidone-iodine, and physiological saline in reducing postoperative infections in TKA. METHODS: The study prospectively included 4743 patients, with Group A (2371, 49.9%) receiving sequential intraoperative application of hydrogen peroxide, povidone-iodine, and physiological saline irrigation of the incision, and Group B (2372, 50.1%) receiving intraoperative application of physiological saline irrigation of the incision only, to collect the patients' baseline data and clinical characteristics, and to statistically assess the incidence of superficial infections and the PJI during the follow up period to evaluate the clinical value of the study. RESULTS: The baseline levels of patients in Groups A and B were comparable. There were 132 (2.8%) lost visits during the study period. The incidence of superficial infections within 30 days after surgery was 0.22% in Group A and 1.17% in Group B, the difference between the two groups was statistically significant (P = 0.007). The incidence of PJI was 0.17% in Group A and 1.26% in Group B, the difference between the two groups was statistically significant (P = 0.0121). CONCLUSION: Sequential application of hydrogen peroxide, povidone-iodine, and physiological saline to irrigate incision in TKA can significantly reduce the incidence of postoperative superficial infections and PJI. The scientific and rational application of this therapy intraoperatively greatly reduces the incidence of PJI and postoperative superficial infections, which is of great benefit to the patient's prognosis.

The mucosal concept in chronic rhinosinusitis: Focus on the epithelial barrier.

Chronic rhinosinusitis (CRS) is a common chronic nasal cavity and sinus disease affecting a growing number of individuals worldwide. Recent advances have shifted our understanding of CRS pathophysiology from a physical obstruction model of ventilation and drainage to a mucosal concept that recognizes the complexities of mucosal immunologic variations and cellular aberrations. A growing number of studies have demonstrated the alteration of the epithelial barrier during inflammatory states. Therefore, the current review has focused on the crucial role of epithelial cells within this mucosal framework in CRS, detailing the perturbed epithelial homeostasis, impaired epithelial cell barrier, dysregulated epithelial cell repair processes, and enhanced interactions between epithelial cells and immune cells. Notably, the utilization of novel technologies, such as single-cell transcriptomics, has revealed the novel functions of epithelial barriers, such as inflammatory memory and neuroendocrine functions. Therefore, this review also emphasizes the importance of epithelial inflammatory memory and the necessity of further investigations into neuroendocrine epithelial cells and neurogenic inflammation in CRS. We conclude by contemplating the prospective benefits of epithelial cell-oriented biological treatments, which are currently under investigation in rigorous randomized, double-blind clinical trials in patients with CRS with nasal polyps.

In Vivo Base Editing of Scn5a Rescues Type 3 Long QT Syndrome in Mice.

BACKGROUND: Pathogenic variants in SCN5A can result in long QT syndrome type 3, a life-threatening genetic disease. Adenine base editors can convert targeted A T base pairs to G C base pairs, offering a promising tool to correct pathogenic variants. METHODS: We generated a long QT syndrome type 3 mouse model by introducing the T1307M pathogenic variant into the Scn5a gene. The adenine base editor was split into 2 smaller parts and delivered into the heart by adeno-associated virus serotype 9 (AAV9-ABEmax) to correct the T1307M pathogenic variant. RESULTS: Both homozygous and heterozygous T1307M mice showed significant QT prolongation. Carbachol administration induced Torsades de Pointes or ventricular tachycardia for homozygous T1307M mice (20%) but not for heterozygous or wild-type mice. A single intraperitoneal injection of AAV9-ABEmax at postnatal day 14 resulted in up to 99.20% Scn5a transcripts corrected in T1307M mice. Scn5a mRNA correction rate >60% eliminated QT prolongation; Scn5a mRNA correction rate <60% alleviated QT prolongation. Partial Scn5a correction resulted in cardiomyocytes heterogeneity, which did not induce severe arrhythmias. We did not detect off-target DNA or RNA editing events in ABEmax-treated mouse hearts. CONCLUSIONS: These findings show that in vivo AAV9-ABEmax editing can correct the variant Scn5a allele, effectively ameliorating arrhythmia phenotypes. Our results offer a proof of concept for the treatment of hereditary arrhythmias.

Dynamic changes of nasal tight junctions in patients with convalescent COVID-19 with allergic rhinitis.

KEY POINTS: Nasal tight junction module score correlates negatively to allergy module score in COVID-19. Omicron variant may slow-down tight junction restoration in patients with AR.

Analysis of HUANG Feng's Medication Rules for Low Back Pain Based on Data Mining / 广州中医药大学学报

Objective To analyze the medication rules of Professor HUANG Feng for the treatment of low back pain using data mining methods.Methods The information of prescriptions for the effective cases of outpatients with low back pain treated by Professor HUANG Feng were collected and screened.Microsoft Excel 2019 was used to analyze the frequency of medication and the distribution of properties,flavors and meridian tropism of the drugs in the included prescription.IBM SPSS Modeler 18.0 was used for association rule analysis,and IBM Statistics 26.0 was used for cluster analysis.Results A total of 239 prescriptions and 75 Chinese medicines were included.There were 23 high-frequency Chinese medicines with the medication frequency being or over 20 times,and the top 10 Chinese medicines were Glycyrrhizae Radix et Rhizoma,vinegar-processed Corydalis Rhizoma,Cibotii Rhizoma,Atractylodis Macrocephalae Rhizoma,Zanthoxyli Radix,salt-processed Achyranthis Bidentatae Radix,Rehmanniae Radix,Dipsaci Radix,Coicis Semen,and Salviae Miltiorrhizae Radix et Rhizoma.The medicines were mainly warm in nature,and were sweet,bitter and pungent in flavor.Most of the drugs had the meridian tropism of liver,stomach and spleen meridians.Among the drug combinations obtained from association rule analysis with the top 20 highest support,vinegar-processed Corydalis Rhizoma,Cibotii Rhizoma,Atractylodis Macrocephalae Rhizoma and Zanthoxyli Radix were the core drugs.Cluster analysis yielded 6 clustering combinations.Conclusion For the treatment of low back pain,Professor HUANG Feng follows the principle of"treatment adapting to the climate,individuality,and environment"and"treating the root cause of the disease",usually adopts the drugs for activating blood,moving qi and relieving pain,nourishing the liver and kidney,and also uses the medicines for replenishing qi and strengthening the spleen.The ideas of HUANG Feng for the treatment of low back pain can be used as a reference for the clinical treatment.

Research status and prospects of organic photocatalysts in algal inhibition and sterilization: a review.

An increasing amount of sewage has been discharged into water bodies in the progression of industrialization and urbanization, causing serious water pollution. Meanwhile, the increase of nutrients in the water induces water eutrophication and rapid growth of algae. Photocatalysis is a common technique for algal inhibition and sterilization. To improve the utilization of visible light and the conversion efficiency of solar energy, more organic photocatalytic materials have been gradually developed. In addition to ultraviolet light, partial infrared light and visible light could also be used by organic photocatalysts compared with inorganic photocatalysts. Simultaneously, organic photocatalysts also exhibit favorable stability. Most organic photocatalysts can maintain a high degradation rate for algae and bacteria after several cycles. There are various organic semiconductors, mainly including small organic molecules, such as perylene diimide (PDI), porphyrin (TCPP), and new carbon materials (fullerene (C60), graphene (GO), and carbon nanotubes (CNT)), and large organic polymers, such as graphite phase carbon nitride (g-C3N4), polypyrrole (PPy), polythiophene (PTH), polyaniline (PANI), and polyimide (PI). In this review, the classification and synthesis methods of organic photocatalytic materials were elucidated. It was demonstrated that the full visible spectral response (400-750 nm) could be stimulated by modifying organic photocatalysts. Moreover, some problems were summarized based on the research status related to algae and bacteria, and corresponding suggestions were also provided for the development of organic photocatalytic materials.

COX6A2 deficiency leads to cardiac remodeling in human pluripotent stem cell-derived cardiomyocytes.

BACKGROUND: Cardiac remodeling is the initiating factor for the development of heart failure, which can result from various cardiomyopathies. Cytochrome c oxidase subunit 6A2 (COX6A2) is one of the components of cytochrome c oxidase that drives oxidative phosphorylation. The pathogenesis of myocardial remodeling caused by COX6A2 deficiency in humans remains unclear because there are no suitable research models. In this study, we established a COX6A2-deficient human cardiac myocyte (CM) model that mimics the human COX6A2 homozygous mutation and determined the effects of COX6A2 dysfunction and its underlying mechanism. METHODS: A human COX6A2 homozygous knockout cardiomyocyte model was established by combining CRISPR/Cas9 gene editing technology and hiPSC-directed differentiation technology. Cell model phenotypic assays were done to characterize the pathological features of the resulting COX6A2-deficient cardiomyocytes. RESULTS: COX6A2 gene knockout did not affect the pluripotency and differentiation efficiency of hiPSCs. Myocardial cells with a COX6A2 gene knockout showed abnormal energy metabolism, increased oxidative stress levels, abnormal calcium transport activity, and decreased contractility. In addition, L-carnitine and trimetazidine significantly improved energy metabolism in the COX6A2-deficient human myocardial model. CONCLUSIONS: We have established a COX6A2-deficient human cardiomyocyte model that exhibits abnormal energy metabolism, elevated oxidative stress levels, abnormal calcium transport, and reduced contractility. This model represents an important tool to gain insight into the mechanism of action of energy metabolism disorders resulting in myocardial remodeling, elucidate the gene-phenotype relationship of COX6A2 deficiency, and facilitate drug screening.

In vivo proximity proteomics uncovers palmdelphin (PALMD) as a Z-line-associated mitigator of isoproterenol-induced cardiac injury.

Z-lines are core ultrastructural organizers of cardiomyocytes that modulate many facets of cardiac pathogenesis. Yet a comprehensive proteomic atlas of Z-line-associated components remain incomplete. Here, we established an adeno-associated virus (AAV)-delivered, cardiomyocyte-specific, proximity-labeling approach to characterize the Z-line proteome in vivo. We found palmdelphin (PALMD) as a novel Z-line-associated protein in both adult murine cardiomyocytes and human pluripotent stem cell-derived cardiomyocytes. Germline and cardiomyocyte-specific palmd knockout mice were grossly normal at baseline but exhibited compromised cardiac hypertrophy and aggravated cardiac injury upon long-term isoproterenol treatment. By contrast, cardiomyocyte-specific PALMD overexpression was sufficient to mitigate isoproterenol-induced cardiac injury. PALMD ablation perturbed transverse tubules (T-tubules) and their association with sarcoplasmic reticulum, which formed the Z-line-associated junctional membrane complex (JMC) essential for calcium handling and cardiac function. These phenotypes were associated with disrupted localization of T-tubule markers caveolin-3 (CAV3) and junctophilin-2 (JPH2) and the reduction of nexilin (NEXN) protein, a crucial Z-line-associated protein that is essential for both Z-line and JMC structures and functions. PALMD was found to interact with NEXN and enhance its protein stability while the Nexn mRNA level was not affected. Together, this study discovered PALMD as a potential target for myocardial protection and highlighted in vivo proximity proteomics as a powerful approach to nominate novel players regulating cardiac pathogenesis. Highlights: In vivo proximity proteomics uncover novel Z-line components that are undetected in in vitro proximity proteomics in cardiomyocytes.PALMD is a novel Z-line-associated protein that is dispensable for baseline cardiomyocyte function in vivo.PALMD mitigates cardiac dysfunction and myocardial injury after repeated isoproterenol insults.PALMD stabilizes NEXN, an essential Z-line-associated regulator of the junctional membrane complex and cardiac systolic function.

Impact of the Built Environment on Residents' Health: Evidence from the China Labor Dynamics Survey in 2016.

In the process of China's rapid urbanization, the health level of residents has been improved to a great extent. However, with the expansion of urban scale and spatial restructuring, a series of urban environmental problems have posed new challenges to public health. However, the impact of the built environment on residents' health is controversial, and the applicability of the conclusions based on western urban sprawl in China is not clear enough. In addition, the exploration of the impact path of the built environment on health is still not comprehensive and in-depth. Based on the China Labor Dynamics Survey (CLDS) in 2016 and relevant statistical yearbook data, this study explored the impact of the built environment at community and urban scale on residents' health and its age heterogeneity and further explored the mediating role of physical exercise, neighborhood support, and community safety. According to the research, the urban and community-built environment has significant impacts on residents' health, and the impact is significantly different at different scales. In addition, there is a significant difference in the impact of built environment factors on residents' health among populations with different life cycles. From the perspective of the impact path, greening coverage can improve residents' self-rated health by enhancing the perceived safety of living in the community. In contrast, the high community population density will not only weaken the degree of neighborhood support but also reduce the perception level of community residential safety, thus damaging residents' health. In short, from the perspective of environmental intervention, the previously mentioned results put forward possible suggestions on strengthening the construction of a healthy living environment so as to maximize the health effectiveness of cities and communities.

Optoelectronic materials as emerging photocatalysts: opportunities in sustainable organic synthesis.

To overcome the energy and environmental crisis, the development of efficient, sustainable photocatalysts to convert inexhaustible solar energy into chemical energy is of great significance. Due to their unique optoelectronic properties, organic electronic materials have been translated into the photocatalytic field. These emerging photocatalysts are attractive because of their metal-free nature, chemical stability, and structural diversity. However, as many small molecules fail to absorb visible light solely, incorporating them into crosslinked frameworks is found to be an effective strategy to extend the conjugation and enhance visible-light absorption. In addition, the photophysical properties of these heterogeneous materials can be adjusted through structural modification and linkage engineering. Finally, these insoluble photocatalysts exhibit good recyclability and reusability. As a representative illustration, this feature article describes recent examples of the use of two types of organic electronic materials including phenothiazine and truxene in heterogeneous photocatalytic organic transformations. The synthesis and key photophysical properties of both organic electronic material-based photocatalysts are discussed combined with specific synthetic applications. We anticipate this feature article will stimulate the implementation of more diverse organic electronic materials in the field of photocatalysis, which may lead to unprecedented synthetic applications.

Evaluation of virulence of Klebsiella pneumoniae using zebrafish behavior as a biological indicator.

INTRODUCTION: Klebsiella pneumoniae is one of the common pathogenic bacteria that can cause infections in hospitals and communities and can cause respiratory, urinary, and other multi-system infections. In recent years, the emergence of highly virulent and drug-resistant Klebsiella pneumoniae has greatly increased the difficulty of treatment for infection. Clinically, it is very important to accurately judge the virulence of isolated Klebsiella pneumoniae for treatment, but there is no better method to evaluate its virulence. METHODS: In this study, zebrafish were used as a model organism, and the swimming distance was used as a detection index to identify clinically isolated Klebsiella pneumoniae. In this study, we selected two different strains of Klebsiella pneumoniae, i.e., NTUH-K2044 and ATCC BAA-1705, with known high and low virulence, respectively, to infect zebrafish juveniles and evaluated their behavioral ability according to different bacterial concentrations and different developmental times. RESULTS: It was found that highly virulent Klebsiella pneumoniae caused a significant decrease in the behavioral ability of zebrafish larvae, while low-virulence Klebsiella pneumoniae had relatively little effect. CONCLUSIONS: These results indicate that it is entirely feasible to assess the virulence of Klebsiella pneumoniae based on behavioral ability.

Real-time programmable metasurface for terahertz multifunctional wave front engineering.

Terahertz (THz) technologies have become a focus of research in recent years due to their prominent role in envisioned future communication and sensing systems. One of the key challenges facing the field is the need for tools to enable agile engineering of THz wave fronts. Here, we describe a reconfigurable metasurface based on GaN technology with an array-of-subarrays architecture. This subwavelength-spaced array, under the control of a 1-bit digital coding sequence, can switch between an enormous range of possible configurations, providing facile access to nearly arbitrary wave front control for signals near 0.34 THz. We demonstrate wide-angle beam scanning with 1° of angular precision over 70 GHz of bandwidth, as well as the generation of multi-beam and diffuse wave fronts, with a switching speed up to 100 MHz. This device, offering the ability to rapidly reconfigure a propagating wave front for beam-forming or diffusively scattered wide-angle coverage of a scene, will open new realms of possibilities in sensing, imaging, and networking.