Disulfidptosis: A new type of cell death.

Disulfidptosis is a novel form of cell death that is distinguishable from established programmed cell death pathways such as apoptosis, pyroptosis, autophagy, ferroptosis, and oxeiptosis. This process is characterized by the rapid depletion of nicotinamide adenine dinucleotide phosphate (NADPH) in cells and high expression of solute carrier family 7 member 11 (SLC7A11) during glucose starvation, resulting in abnormal cystine accumulation, which subsequently induces andabnormal disulfide bond formation in actin cytoskeleton proteins, culminating in actin network collapse and disulfidptosis. This review aimed to summarize the underlying mechanisms, influencing factors, comparisons with traditional cell death pathways, associations with related diseases, application prospects, and future research directions related to disulfidptosis.

Two-stage deep-learning-based colonoscopy polyp detection incorporating fisheye and reflection correction.

BACKGROUND AND AIM: Colonoscopy is a useful method for the diagnosis and management of colorectal diseases. Many computer-aided systems have been developed to assist clinicians in detecting colorectal lesions by analyzing colonoscopy images. However, fisheye-lens distortion and light reflection in colonoscopy images can substantially affect the clarity of these images and their utility in detecting polyps. This study proposed a two-stage deep-learning model to correct distortion and reflections in colonoscopy images and thus facilitate polyp detection. METHODS: Images were collected from the PolypSet dataset, the Kvasir-SEG dataset, and one medical center's patient archiving and communication system. The training, validation, and testing datasets comprised 808, 202, and 1100 images, respectively. The first stage involved the correction of fisheye-related distortion in colonoscopy images and polyp detection, which was performed using a convolutional neural network. The second stage involved the use of generative and adversarial networks for correcting reflective colonoscopy images before the convolutional neural network was used for polyp detection. RESULTS: The model had higher accuracy when it was validated using corrected images than when it was validated using uncorrected images (96.8% vs 90.8%, P < 0.001). The model's accuracy in detecting polyps in the Kvasir-SEG dataset reached 96%, and the area under the receiver operating characteristic curve was 0.94. CONCLUSION: The proposed model can facilitate the clinical diagnosis of colorectal polyps and improve the quality of colonoscopy.

Impact of coronavirus disease 2019 (COVID-19) on antimicrobial resistance among major pathogens causing healthcare-associated infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused great impact on healthcare systems, including antibiotic usage and multi-drug resistant (MDR) bacterial infections at hospitals. We aim to investigate the trends of antimicrobial resistance among the major pathogens causing healthcare-associated infection (HAI) at intensive care units (ICU). MATERIAL AND METHODS: The demographic characteristics of hospitalization, usage of antimicrobial agents, counted by half-an-year DID (defined daily dose per 1000 patient-days), and HAI density of five major MDR bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumoniae (CRKP), and carbapenem-resistant Pseudomonas aeruginosa (CRPA), of ICU patients at a medical center in Taiwan during January 2017 to December 2021 were collected and analyzed. RESULTS: The total antibiotic usage, counted by DID, had a significant increasing trend, before COVID-19 occurrence in 2017-2019, but no further increase during the pandemic period in 2020-2021. However, comparing the two time periods, antibiotics consumption was significantly increased during pandemic period. There was no significant change of HAI density in MRSA, VRE, CRAB, CRKP, and CRPA, comparing the pandemic to the pre-pandemic period. Although, CRKP and CRPA infection rates were increasing during the pre-pandemic period, there was no further increase of CRKP and CRPA HAI rates during the pandemic period. CONCLUSION: During COVID-19 pandemic, there was no significant increase in HAI density of five major MDR bacteria at ICU in Taiwan, despite increased antibiotic usage. Strict infection prevention measures for COVID-19 precautions and sustained antimicrobial stewardship probably bring these effects.

High-Precision Atom Interferometer-Based Dynamic Gravimeter Measurement by Eliminating the Cross-Coupling Effect.

A dynamic gravimeter with an atomic interferometer (AI) can perform absolute gravity measurements with high precision. AI-based dynamic gravity measurement is a type of joint measurement that uses an AI sensor and a classical accelerometer. The coupling of the two sensors may degrade the measurement precision. In this study, we analyzed the cross-coupling effect and introduced a recovery vector to suppress this effect. We improved the phase noise of the interference fringe by a factor of 1.9 by performing marine gravity measurements using an AI-based gravimeter and optimizing the recovery vector. Marine gravity measurements were performed, and high gravity measurement precision was achieved. The external and inner coincidence accuracies of the gravity measurement were ±0.42 mGal and ±0.46 mGal after optimizing the cross-coupling effect, which was improved by factors of 4.18 and 4.21 compared to the cases without optimization.

Prevention and Potential Treatment Strategies for Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) is a significant viral pathogen that causes respiratory infections in infants, the elderly, and immunocompromised individuals. RSV-related illnesses impose a substantial economic burden worldwide annually. The molecular structure, function, and in vivo interaction mechanisms of RSV have received more comprehensive attention in recent times, and significant progress has been made in developing inhibitors targeting various stages of the RSV replication cycle. These include fusion inhibitors, RSV polymerase inhibitors, and nucleoprotein inhibitors, as well as FDA-approved RSV prophylactic drugs palivizumab and nirsevimab. The research community is hopeful that these developments might provide easier access to knowledge and might spark new ideas for research programs.

Development of a multispectral fluorescence LiDAR for point cloud segmentation of plants.

The accelerating development of high-throughput plant phenotyping demands a LiDAR system to achieve spectral point cloud, which will significantly improve the accuracy and efficiency of segmentation based on its intrinsic fusion of spectral and spatial data. Meanwhile, a relatively longer detection range is required for platforms e.g., unmanned aerial vehicles (UAV) and poles. Towards the aims above, what we believe to be, a novel multispectral fluorescence LiDAR, featuring compact volume, light weight, and low cost, has been proposed and designed. A 405 nm laser diode was employed to excite the fluorescence of plants, and the point cloud attached with both the elastic and inelastic signal intensities that was obtained through the R-, G-, B-channels of a color image sensor. A new position retrieval method has been developed to evaluate far field echo signals, from which the spectral point cloud can be obtained. Experiments were designed to validate the spectral/spatial accuracy and the segmentation performance. It has been found out that the values obtained through the R-, G-, B-channels are consistent with the emission spectrum measured by a spectrometer, achieving a maximum R2 of 0.97. The theoretical spatial resolution can reach up to 47 mm and 0.7 mm in the x- and y-direction at a distance of around 30 m, respectively. The values of recall, precision, and F score for the segmentation of the fluorescence point cloud were all beyond 0.97. Besides, a field test has been carried out on plants at a distance of about 26 m, which further demonstrated that the multispectral fluorescence data can significantly facilitate the segmentation process in a complex scene. These promising results prove that the proposed multispectral fluorescence LiDAR has great potential in applications of digital forestry inventory and intelligent agriculture.

The association of social support and hope with self-stigma and perceived recovery among people with schizophrenia: The serial mediation effect.

BACKGROUND: It is essential to assist individuals with a mental illness who have achieved clinical recovery in their personal recovery. Understanding the relationship between self-stigma and social support and the effects on perceived recovery can be valuable for clinical professionals in helping patients lead meaningful lives. AIM: To examine the serial mediating roles of social support and perceived hope in self-stigma and the effects on perceived recovery. DESIGN: A cross-sectional study. METHODS: The study was conducted from September 2019 to June 2020. One hundred and fifty-seven patients with schizophrenia in seven chronic rehabilitation wards were enrolled. Each patient had a Positive and Negative Syndrome Scale score ≤ 60 points, and they regularly participated in occupational rehabilitation. Research tools included demographic data, the Internalized Stigma of Mental Illness Scale (ISMIS), Multidimensional Scale of Perceived Social Support (MSPSS), Herth Hope Index (HHI), and Perceived Recovery Inventory (PRI). IBM SPSS 24.0 was used to analyse the data. Pearson correlation was used to analyse the relationships between variables, and models 4 and 6 of PROCESS macro V3.4 for SPSS were used to examine the mediation model. RESULTS: The results indicated that self-stigma and perceived recovery in patients with schizophrenia are negatively correlated, that peer support and perceived hope mediate the relationship between them, and that peer support and perceived hope also have a statistically significant serial mediating effect. CONCLUSION: The serial mediation effect of peer support and perceived hope on the relationship between self-stigma and perceived recovery was statistically significant in this study. IMPACT: This research delves into strategies to assist psychiatric patients in reducing self-stigma and achieving recovery. The findings underscore the heightened significance of peer support for patients in rehabilitative wards and offer valuable insights for medical staff. REPORTING METHOD: STROBE checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

An Approach of Vibration Compensation for Atomic Gravimeter under Complex Vibration Environment.

Atomic gravimeter has been more frequently applied under complex and dynamic environments, but its measurement accuracy is seriously hampered by vibration-induced noise. In this case, vibration compensation provides a way to enhance the accuracy of gravity measurements by correcting the phase noise that resulted from the vibration of a Raman reflector, and improving the fitting of an interference fringe. An accurate estimation of the transfer function of vibration between the Raman reflector and the sensor plays a significant role in optimizing the effect of vibration compensation. For this reason, a vibration compensation approach was explored based on EO (equilibrium optimizer) for estimating the transfer function simplified model of a Raman reflector, and it was used to correct the interference fringe of an atomic gravimeter. The test results revealed that this approach greatly restored the actual vibration of the Raman reflector in a complex vibration environment. With a vibration compensation algorithm, it achieved the correction and fitting of the original interference fringe. In general, it dramatically reduced the RMSE (root mean square error) at the time of fitting and significantly improved the residual error in the gravity measurement. Compared with other conventional algorithms, such as GA (genetic algorithm) and PSO (particle swarm optimization), this approach realized a faster convergence and better optimization, so as to ensure more accurate gravity measurements. The study of this vibration compensation approach could provide a reference for the application of an atomic gravimeter in a wider and more complex environment.

Allicin Alleviated LPS-Induced Mastitis via the TLR4/NF-κB Signaling Pathway in Bovine Mammary Epithelial Cells.

Dairy farming is the most important economic activity in animal husbandry. Mastitis is the most common disease in dairy cattle and has a significant impact on milk quality and yield. The natural extract allicin, which is the main active ingredient of the sulfur-containing organic compounds in garlic, has anti-inflammatory, anticancer, antioxidant, and antibacterial properties; however, the specific mechanism underlying its effect on mastitis in dairy cows needs to be determined. Therefore, in this study, whether allicin can reduce lipopolysaccharide (LPS)-induced inflammation in the mammary epithelium of dairy cows was investigated. A cellular model of mammary inflammation was established by pretreating bovine mammary epithelial cells (MAC-T) with 10 µg/mL LPS, and the cultures were then treated with varying concentrations of allicin (0, 1, 2.5, 5, and 7.5 µM) added to the culture medium. MAC-T cells were examined using RT-qPCR and Western blotting to determine the effect of allicin. Subsequently, the level of phosphorylated nuclear factor kappa-B (NF-κB) was measured to further explore the mechanism underlying the effect of allicin on bovine mammary epithelial cell inflammation. Treatment with 2.5 µM allicin considerably decreased the LPS-induced increase in the levels of the inflammatory cytokines interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) and inhibited activation of the NOD-like receptor protein 3 (NLRP3) inflammasome in cow mammary epithelial cells. Further research revealed that allicin also inhibited the phosphorylation of inhibitors of nuclear factor kappa-B-α (IκB-α) and NF-κB p65. In mice, LPS-induced mastitis was also ameliorated by allicin. Therefore, we hypothesize that allicin alleviated LPS-induced inflammation in the mammary epithelial cells of cows probably by affecting the TLR4/NF-κB signaling pathway. Allicin will likely become an alternative to antibiotics for the treatment of mastitis in cows.

Reflective metalens with an enhanced off-axis focusing performance.

Metalenses are one of the most promising metasurface applications. However, all-dielectric reflective metalenses are rarely studied, especially regarding their off-axis focusing performance. After experimentally studying the material optical properties in this work, we propose reflective metalens based on titanium dioxide (TiO2) and silicon dioxide (SiO2), which operate at a visible wavelength of 0.633 µm. Unlike conventional reflective metalenses based on metallic mirrors, the proposed device was designed based on a modified parabolic phase profile and was integrated onto a dielectric distributed Bragg reflector periodic structure to achieve high reflectivity with five dielectric pairs. The focusing efficiency characteristics of the metalens were experimentally studied for beam angles of incidence between 0∘ and 30∘. The results reveal that the focusing efficiency for the modified metalens design remains higher than 54%, which is higher than 50%, making it promising for photonic miniaturization and integration.

Localized surface plasmon resonance-enhanced solar-blind Al0.4Ga0.6N MSM photodetectors exhibiting high-temperature robustness.

The appealing properties of tunable direct wide bandgap, high-temperature robustness and chemical hardness, make AlxGa1-xN a promising candidate for fabricating robust solar-blind photodetectors (PDs). In this work, we have utilized the optical phenomenon of localized surface plasmon resonance (LSPR) in metal nanoparticles (NPs) to significantly enhance the performance of solar-blind Al0.4Ga0.6N metal-semiconductor-metal PDs that exhibit high-temperature robustness. We demonstrate that the presence of palladium (Pd) NPs leads to a remarkable enhancement by nearly 600, 300, and 462%, respectively, in the photo-to-dark current ratio (PDCR), responsivity, and specific detectivity of the Al0.4Ga0.6N PD at the wavelength of 280 nm. Using the optical power density of only 32µW cm-2at -10 V, maximum values of ∼3 × 103, 2.7 AW-1, and 2.4 × 1013Jones are found for the PDCR, responsivity and specific detectivity, respectively. The experimental observations are supported by finite difference time domain simulations, which clearly indicate the presence of LSPR in Pd NPs decorated on the surface of Al0.4Ga0.6N. The mechanism behind the enhancement is investigated in detail, and is ascribed to the LSPR induced effects, namely, improved optical absorption, enhanced local electric field and LSPR sensitization effect. Moreover, the PD exhibits a stable operation up to 400 K, thereby exhibiting the high-temperature robustness desirable for commercial applications.

Novel hydroxyl carboximates derived from ß-elemene: design, synthesis and anti-tumour activities evaluation.

A series of novel N-alkyl-N-hydroxyl carboximates derived from ß-elemene were fortuitously discovered. Most of them showed more potent anti-proliferative activities than their lead compound ß-elemene (1). Notably, compound 11i exhibited significant inhibitory effects on the proliferation of three lung cell lines (H1975, A549 and H460) and several other tumour cell lines (H1299, U87MG, MV4-11, and SU-DHL-2). Preliminary mechanistic studies revealed that compound 11i could significantly induce cell apoptosis. Further in vivo study in the H460 xenograft mouse model validated the anti-tumour activities of 11i with a greater tumour growth inhibition (TGI, 68.3%) than ß-elemene and SAHA (50.1% and 55.9% respectively) at 60 mg/kg ip dosing, without obvious body weight loss and toxicity. Thus, such N-alkyl-N-hydroxyl carboximate class of compounds exemplified as 11i demonstrated potent anticancer activities both in vitro and in vivo, and should warrant further investigation for potential anticancer therapy.

Effects and Prospects of the Vibration Isolation Methods for an Atomic Interference Gravimeter.

An atomic interference gravimeter (AIG) is of great value in underwater aided navigation, but one of the constraints on its accuracy is vibration noise. For this reason, technology must be developed for its vibration isolation. Up to now, three methods have mainly been employed to suppress the vibration noise of an AIG, including passive vibration isolation, active vibration isolation and vibration compensation. This paper presents a study on how vibration noise affects the measurement of an AIG, a review of the research findings regarding the reduction of its vibration, and the prospective development of vibration isolation technology for an AIG. Along with the development of small and movable AIGs, vibration isolation technology will be better adapted to the challenging environment and be strongly resistant to disturbance in the future.

[Regulation of Toll-like receptors and their downstream factors by butyrate].

Butyrate, normally produced by probiotics in the gut, not only provides energy for cells, but also changes the phosphorylation, acetylation and methylation levels of many proteins in cells. As a result, it affects the expression of many genes and the transmission of cell signals. Through G protein-coupled receptors, butyrate promotes the secretion of intestinal mucus and the formation of epithelial barriers, and attenuates the impacts of the pathogenic bacteria and their metabolites on human body. The Toll-like receptors (TLRs) are a group of pattern recognition receptors, and their activation causes the translocation of nuclear factor κB (NF-κB) from the cytoplasm to the nucleus and eventually leads to expression and secretion of various pro-inflammatory factors and chemokines. The expression of TLRs is also involved in the pathogenesis of some inflammatory diseases and tumors. The purpose of this review is to summarize the effects of butyrate on TLRs and their downstream signaling pathways. We not only summarized the production of butyrate, the expression of TLRs and the influence of their interaction on the body under the conditions of inflammation and tumor, but also discussed the potential role of butyrate as a bacterial metabolite in the treatments of some human diseases.

Development of an In Vitro 3D Model for Investigating Ligamentum Flavum Hypertrophy.

BACKGROUND: Ligamentum flavum hypertrophy (LFH) is among the most crucial factors in degenerative lumbar spinal stenosis, which can cause back pain, lower extremity pain, cauda equina syndrome and neurogenic claudication. The exact pathogenesis of LFH remains elusive despite extensive research. Most in vitro studies investigating LFH have been carried out using conventional two-dimensional (2D) cell cultures, which do not resemble in vivo conditions, as they lack crucial pathophysiological factors found in three-dimensional (3D) LFH tissue, such as enhanced cell proliferation and cell cluster formation. In this study, we generated ligamentum flavum (LF) clusters using spheroid cultures derived from primary LFH tissue. RESULTS: The cultured LF spheroids exhibited good viability and growth on an ultra-low attachment 96-well plate (ULA 96-plate) platform according to live/dead staining. Our results showed that the 100-cell culture continued to grow in size, while the 1000-cell culture maintained its size, and the 5000-cell culture exhibited a decreasing trend in size as the culture time increased; long-term culture was validated for at least 28 days. The LF spheroids also maintained the extracellular matrix (ECM) phenotype, i.e., fibronectin, elastin, and collagen I and III. The 2D culture and 3D culture were further compared by cell cycle and Western blot analyses. Finally, we utilized hematoxylin and eosin (H&E) staining to demonstrate that the 3D spheroids resembled part of the cell arrangement in LF hypertrophic tissue. CONCLUSIONS: The developed LF spheroid model has great potential, as it provides a stable culture platform in a 3D model that can further improve our understanding of the pathogenesis of LFH and has applications in future studies.

Synthesis of Polysubstituted Cyclopentene and Cyclopenta[ b]carbazole Analogues from Unsymmetrical 4-Arylidene-3,6-diarylhex-2-en-5-ynal and Indole Derivatives via an Iodine Mediated Electrocyclization Reaction.

An efficient method for the synthesis of polysubstituted cyclopentene and cyclopenta[ b]carbazole derivatives through the iodine-promoted electrocyclization of substituted indoles and 4-arylidene-3,6-diarylhex-2-en-5-ynal derivatives is reported. Polysubstituted cyclopentene derivatives were produced through 4π electrocyclization reactions with indole, 7-methylindole, and 5-bromoindole as coupling partners, whereas cyclopenta[ b]carbazole derivatives were produced via 6π electrocyclization in the case of methoxy (-OMe)-substituted indoles. The methods reported herein diastereo- and regioselectively proceed under straightforward and mild conditions.

A fully distributed traffic allocation algorithm for nonconcave utility maximization in connectionless communication networks.

As IP video services have emerged to be the predominant Internet application, how to optimize the Internet resource allocation, while satisfying the quality of experience (QoE) for users of video services and other Internet applications becomes a challenge. This is because the QoE perceived by a user of video services can be characterized by a staircase function of the data rate, which is nonconcave and hence it is "hard" to find the optimal operating point. The work in this paper aims at tackling this challenge. It considers the packet routing problem among multiple end points in packet switching networks based on a connectionless, hop-by-hop forwarding paradigm. We model this traffic allocation problem using a fluid flow model and let the link bandwidth be the only resource to be shared. To maximize the utilization of resources and avoid congestion, we formulate the problem as a network utility maximization problem. More precisely, the objective of this paper is to design a Fully Distributed Traffic Allocation Algorithm (FDTAA) that is applicable to a large class of nonconcave utility functions. Moreover, FDTAA runs in a fully distributed way: it enables each router to independently address and route each data unit using immediate local information in parallel, without referring to any global information of the communication network. FDTAA requires minimum computation workload, since the routing decision made at each router is solely based on the destination information carried in each unit. In addition, the network utility values corresponding to the FDTAA iterate sequence converge to the optimal network utility value at the rate of (1/K), where K is the iteration counter. These theoretical results are exemplified by the simulation performed on an example communication network.

[The regulation of Na+/H+ exchangers by Toll-like receptors under inflammation].

Toll-like receptors (TLRs) can be recognized and activated by different pathogen associated molecular patterns (PAMPs), which induce innate immune response and inflammation of the body. Na+/H+ exchangers (NHEs) not only play roles in the regulation of cellular pH and cell volume, maintenance of the cavity microenvironment and nutrients absorption, but also are related to cell proliferation, migration and apoptosis. The activity and membrane protein expression of NHEs are inhibited under the inflammation condition. It has been shown that the activation of TLR2 in colon epithelial cells can inhibit the activity of NHE1 through MyD88 independent pathway, which involves the recruitment of Src and the phosphorylation of PI3Ks. Other studies on intestinal macrophage showed long-term LPS stimulation can induce TLR4 activation through MyD88-dependent pathway (TLR4/MyD88/NF-κB) and induce inflammation and degeneration of intracellular NHE1, which leads to NHE1 activity inhibition. But short-term LPS exposure increases the activity and protein expression of NHE1. The activation of TLR5 increases the activity of NHE3. The activity and/or expression of NHE3 in intestinal macrophages in colitis patients and model animals were decreased. In renal tubular epithelial cells, basolateral LPS stimulation inhibits luminal NHE3 activation through TLR4/MyD88-dependent MAPK/ERK signaling pathway. And LPS stimulation on the lumen side activates TLR4/MyD88-dependent PI3K-AKT-mTOR signaling pathway, which results in the inhibition of NHE1 activity in basolateral side, and then affects the NHE3 function of the lumen side.

V-band gapless OFDM RoF system with power detector down-conversion and novel Volterra nonlinear filtering.

This Letter presents a V-band gapless orthogonal frequency division multiplexing (OFDM) RoF system at 60 GHz employing a power detector to support vector signal down-conversion. Additional RF tone is generated and transmitted from a central station to replace the local oscillator at a wireless receiver for power detector down-conversion. To enhance the spectrum efficiency, the gap between the OFDM signal and the RF tone is not needed. However, the down-converted signal will suffer signal-to-signal interference (SSBI). In this Letter, we propose and successfully employ a novel Volterra nonlinear compensation to mitigate SSBI, resulting in a 22% data rate improvement with a bit-loading algorithm.

Regularly patterned multi-section GaN nanorod arrays grown with a pulsed growth technique.

The growth of regularly patterned multi-section GaN nanorod (NR) arrays based on a pulsed growth technique with metalorganic chemical vapor deposition is demonstrated. Such an NR with multiple sections of different cross-sectional sizes is formed by tapering a uniform cross section to another through stepwise decreasing of the Ga supply duration to reduce the size of the catalytic Ga droplet. Contrast line structures are observed in either a scanning electron microscopy or transmission electron microscopy image of an NR. Such a contrast line-marker corresponds to a thin Ga-rich layer formed at the beginning of GaN precipitation of a pulsed growth cycle and illustrates the boundary between two successive growth cycles in pulsed growth. By analyzing the geometry variation of the contrast line-markers, the morphology evolution in the growth of a multi-section NR, including a tapering process, can be traced. Such a morphology variation is controlled by the size of the catalytic Ga droplet and its coverage range on the slant facets at the top of an NR. The comparison of emission spectra between single-, two-, and three-section GaN NRs with sidewall InGaN/GaN quantum wells indicates that a multi-section NR can lead to a significantly broader sidewall emission spectrum.