Discovery of quaternized pyridine-thiazole-ruthenium complexes as potent anti-Staphylococcus aureus agents.

Quaternization of ruthenium complexes may be a promising strategy for the development of new antibiotics. In response to the increasing bacterial resistance, we integrated the quaternary amine structure into the design of ruthenium complexes and evaluated their antibacterial activity. All the ruthenium complexes showed good antibacterial activity against the tested Staphylococcus aureus (S. aureus). Ru-8 was the most effective antibacterial agent that displayed excellent antibacterial activity against S. aureus (MIC = 0.78-1.56 µg/mL). In vitro experiments showed that all nine ruthenium complexes had low hemolytic toxicity to rabbit erythrocytes. Notably, Ru-8 was found to disrupt bacterial cell membranes, alter their permeability, and induce ROS production in bacteria, all the above leading to the death of bacteria without inducing drug resistance. To further explore the antibacterial activity of Ru-8in vivo, we established a mouse skin wound infection model and a G. mellonella larvae infection model. Ru-8 exhibited significant antibacterial efficacy against S. aureus in vivo and low toxicity to mouse tissues. The Ru-8 showed low toxicity to Raw264.7 cells (mouse monocyte macrophage leukemia cells). This study indicates that the ruthenium complex ruthenium quaternary was a promising strategy for the development of new antibacterial agents.

Hallmarks of perineural invasion in pancreatic ductal adenocarcinoma: new biological dimensions.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant tumor with a high metastatic potential. Perineural invasion (PNI) occurs in the early stages of PDAC with a high incidence rate and is directly associated with a poor prognosis. It involves close interaction among PDAC cells, nerves and the tumor microenvironment. In this review, we detailed discuss PNI-related pain, six specific steps of PNI, and treatment of PDAC with PNI and emphasize the importance of novel technologies for further investigation.

Fabrication and Characterization of PLA/PBAT Blends, Blend-Based Nanocomposites, and Their Supercritical Carbon Dioxide-Induced Foams.

In this study, a twin-screw extruder was used to fabricate poly(lactic acid) (PLA)/poly(butylene adipate-co-terephthalate) (PBAT) blends and blend-based nanocomposites with carbon nanotube (CNT) or nanocarbon black (CB) as nanofillers. The fabricated samples were subsequently treated with supercritical carbon dioxide (scCO2) to fabricate the corresponding foams. Bi-phasic morphology and selective distribution of CNTs or CBs in the PBAT phase were observed in the blends/composites through scanning electron microscopy. After the scCO2 treatment, the selective foaming of the PBAT phase in the prepared blends/composites was confirmed. The cellular structure of PBAT phase in scCO2-treated blends is similar to the size/shape of PBAT domains in untreated blends or treated neat PBAT foam. The addition of CNTs or CBs in the blends led to a slight reduction in cell size of the foamed PBAT phase, demonstrating CNT/CB-induced cell nucleation. Differential scanning calorimetry (DSC) results showed that CNTs and CBs played as nucleating agents and increased the initial crystallization temperature up to 14 °C compared with neat PBAT for PBAT in different composites during cooling. The scCO2 treatment induced the bimodal stability of PBAT crystals in different samples, which melted mainly in two temperature regions in DSC studies. Thermogravimetric analyses revealed that compared with parent blends, the addition of CNTs or CBs increased the temperature at 80 wt.% loss (degradation of PBAT portion) up to 6 °C. The electrical resistivity decreased by more than six orders of magnitude for certain CNT- or CB-added composites compared with the parent blends. The hardness of the blends slightly increased after forming the corresponding composites and then declined after the scCO2 treatment.

Global Trends in Orthopedic Biofilm Research: A Bibliometric Analysis of 1994-2022.

Objective: Bibliometric analysis is commonly used to visualize the knowledge foundation, trends, and patterns in a specific scientific field by performing a quantitative evaluation of the relevant literature. The purpose of this study was to perform a bibliometric analysis of recent studies in the field of orthopedic biofilm research and identify its current trends and hotspots. Methods: Research studies were retrieved from the Web of Science Core Collection and Scopus databases and analyzed in bibliometrix with R package (4.2.2). Results: A total of 2426 literature were included in the study. Journal of orthopaedic research and Clinical orthopaedics and related research ranked first in terms of productivity and impact, with 57 published articles and 32 h-index, respectively. Trampuz A, Ohio State Univ and the United States ranked as the most productive authors, institutions, and countries. Biofilm formation, role of sonication, biomaterial mechanism and antibiotic loading have been investigated as the trend and hotspots in the field of orthopedic biofilm research. Conclusion: This study provides a thorough overview of the state of the art of current orthopedic biofilm research and offers valuable insights into recent trends and hotspots in this field.

Regulatory mechanisms of amino acids in ferroptosis.

Ferroptosis, an iron-dependent non-apoptotic regulated cell death process, is associated with the pathogenesis of various diseases. Amino acids, which are indispensable substrates of vital activities, significantly regulate ferroptosis. Amino acid metabolism is involved in maintaining iron and lipid homeostasis and redox balance. The regulatory effects of amino acids on ferroptosis are complex. An amino acid may exert contrasting effects on ferroptosis depending on the context. This review systematically and comprehensively summarized the distinct roles of amino acids in regulating ferroptosis and highlighted the emerging opportunities to develop clinical therapeutic strategies targeting amino acid-mediated ferroptosis.

NeuroSeg-III: efficient neuron segmentation in two-photon Ca2+ imaging data using self-supervised learning.

Two-photon Ca2+ imaging technology increasingly plays an essential role in neuroscience research. However, the requirement for extensive professional annotation poses a significant challenge to improving the performance of neuron segmentation models. Here, we present NeuroSeg-III, an innovative self-supervised learning approach specifically designed to achieve fast and precise segmentation of neurons in imaging data. This approach consists of two modules: a self-supervised pre-training network and a segmentation network. After pre-training the encoder of the segmentation network via a self-supervised learning method without any annotated data, we only need to fine-tune the segmentation network with a small amount of annotated data. The segmentation network is designed with YOLOv8s, FasterNet, efficient multi-scale attention mechanism (EMA), and bi-directional feature pyramid network (BiFPN), which enhanced the model's segmentation accuracy while reducing the computational cost and parameters. The generalization of our approach was validated across different Ca2+ indicators and scales of imaging data. Significantly, the proposed neuron segmentation approach exhibits exceptional speed and accuracy, surpassing the current state-of-the-art benchmarks when evaluated using a publicly available dataset. The results underscore the effectiveness of NeuroSeg-III, with employing an efficient training strategy tailored for two-photon Ca2+ imaging data and delivering remarkable precision in neuron segmentation.

Engineering Glucosamine-6-Phosphate Synthase to Achieve Efficient One-Step Biosynthesis of Glucosamine.

As an important functional monosaccharide, glucosamine (GlcN) is widely used in fields such as medicine, food nutrition, and health care. Here, we report a distinct GlcN biosynthesis method that utilizes engineered Bacillus subtilis glucosamine-6-phosphate synthase (BsGlmS) to convert D-fructose to directly generate GlcN. The best variant obtained by using a combinatorial active-site saturation test/iterative saturation mutagenesis (CAST/ISM) strategy was a quadruple mutant S596D/V597G/S347H/G299Q (BsGlmS-BK19), which has a catalytic activity 1736-fold that of the wild type toward D-fructose. Upon using mutant BK19 as a whole-cell catalyst, D-fructose was converted into GlcN with 65.32% conversion in 6 h, whereas the wild type only attained a conversion rate of 0.31% under the same conditions. Molecular docking and molecular dynamics simulations were implemented to provide insights into the mechanism underlying the enhanced activity of BK19. Importantly, the BsGlmS-BK19 variant specifically catalyzes D-fructose without the need for phosphorylated substrates, representing a significant advancement in GlcN biosynthesis.

Automatic segmentation of dura for quantitative analysis of lumbar stenosis: A deep learning study with 518 CT myelograms.

BACKGROUND: The diagnosis of lumbar spinal stenosis (LSS) can be challenging because radicular pain is not often present in the culprit-level localization. Accurate segmentation and quantitative analysis of the lumbar dura on radiographic images are key to the accurate differential diagnosis of LSS. The aim of this study is to develop an automatic dura-contouring tool for radiographic quantification on computed tomography myelogram (CTM) for patients with LSS. METHODS: A total of 518 CTM cases with or without lumbar stenosis were included in this study. A deep learning (DL) segmentation algorithm 3-dimensional (3D) U-Net was deployed. A total of 210 labeled cases were used to develop the dura-contouring tool, with the ratio of the training, independent testing, and external validation datasets being 150:30:30. The Dice score (DCS) was the primary measure to evaluate the segmentation performance of the 3D U-Net, which was subsequently developed as the dura-contouring tool to segment another unlabeled 308 CTM cases with LSS. Automatic masks of 446 slices on the stenotic levels were then meticulously reviewed and revised by human experts, and the cross-sectional area (CSA) of the dura was compared. RESULTS: The mean DCS of the 3D U-Net were 0.905 ± 0.080, 0.933 ± 0.018, and 0.928 ± 0.034 in the five-fold cross-validation, the independent testing, and the external validation datasets, respectively. The segmentation performance of the dura-contouring tool was also comparable to that of the second observer (the human expert). With the dura-contouring tool, only 59.0% (263/446) of the automatic masks of the stenotic slices needed to be revised. In the revised cases, there were no significant differences in the dura CSA between automatic masks and corresponding revised masks (p = 0.652). Additionally, a strong correlation of dura CSA was found between the automatic masks and corresponding revised masks (r = 0.805). CONCLUSIONS: A dura-contouring tool was developed that could automatically segment the dural sac on CTM, and it demonstrated high accuracy and generalization ability. Additionally, the dura-contouring tool has the potential to be applied in patients with LSS because it facilitates the quantification of the dural CSA on stenotic slices.

STPoseNet: A real-time spatiotemporal network model for robust mouse pose estimation.

Animal behavior analysis plays a crucial role in contemporary neuroscience research. However, the performance of the frame-by-frame approach may degrade in scenarios with occlusions or motion blur. In this study, we propose a spatiotemporal network model based on YOLOv8 to enhance the accuracy of key-point detection in mouse behavioral experimental videos. This model integrates a time-domain tracking strategy comprising two components: the first part utilizes key-point detection results from the previous frame to detect potential target locations in the subsequent frame; the second part employs Kalman filtering to analyze key-point changes prior to detection, allowing for the estimation of missing key-points. In the comparison of pose estimation results between our approach, YOLOv8, DeepLabCut and SLEAP on videos of three mouse behavioral experiments, our approach demonstrated significantly superior performance. This suggests that our method offers a new and effective means of accurately tracking and estimating pose in mice through spatiotemporal processing.

The effect of childhood harshness and unpredictability on Internet addiction among college students: The mediating effect of self-control.

College students are inevitably online and at risk of becoming addicted. Life history theory provides an explanatory framework for individual differences in Internet addiction, and childhood harshness and unpredictability may be important antecedents. However, it is unclear whether and how childhood harshness and/or unpredictability affect Internet addiction during college. In this study, we recruited 483 Chinese college students and assessed their childhood harshness, unpredictability, self-control, and Internet addiction. The results of path analysis showed that childhood unpredictability was positively associated with Internet addiction among college students and was partially mediated by self-control. The effect of harshness on Internet addiction showed a suppression effect, i.e., the direct effect of harshness on Internet addiction was negative and the indirect effect through self-control was positive. This suggests that the high risk of Internet addiction stems from harshness and unpredictability in childhood, but that the effects of these factors are independent and distinct. Self-control plays an important role in this process, but many internal mechanisms remain to be tested in future research.

[Research progress on ferroptosis in tumor immunity].

Ferroptosis is a novel form of cell death that is induced by excessive accumulation of ferrous ions and lipid peroxides. It triggers the release of damage-associated molecular patterns through autophagy-dependent mechanisms, serving as an adjunct to immunogenic cell death and activating both adaptive and innate immunity. In the tumor microenvironment, the regulation and influence of tumor cells and immune cells undergoing ferroptosis are regulated by various factors, which plays a crucial role in tumor development, treatment, and prognosis. This article provides an overview of the biological effects of ferroptosis on immune cells such as T cells, macrophages, neutrophils and B cells and tumor cells in the tumor microenvironment.

Polypyridyl ruthenium complexes with benzothiazole moiety as membrane disruptors and anti-resistance agents for Staphylococcus aureus.

Developing new antimicrobials to combat drug-resistant bacterial infections is necessary due to the increasing problem of bacterial resistance. In this study, four metallic ruthenium complexes modified with benzothiazoles were designed, synthesized and subjected to bio-evaluated. Among them, Ru-2 displayed remarkable inhibitory activity against Staphylococcus aureus (S. aureus) with a minimum inhibitory concentration (MIC) of 1.56 µg/mL. Additionally, it showcased low hemolytic toxicity (HC50 > 200 µg/mL) and the ability to effectively eradicate S. aureus without fostering drug resistance. Further investigation into the antibacterial mechanism suggested that Ru-2 may target the phospholipid component of S. aureus, leading to the disruption of the bacterial cell membrane and subsequent leakage of cell contents (nucleic acid, protein, and ONPG), ultimately resulting in the death of the bacterial cell. In vivo studies, both the G. mellonella larvae and the mouse skin infection models were conducted, indicated that Ru-2 could potentially serve as a viable candidate for the treatment of S. aureus infection. It exhibited no toxic or side effects on normal tissues. The results suggest that benzothiazole-modified ruthenium complexes may have potential as membrane-active antimicrobials against drug-resistant bacterial infections.

Antibacterial and self-healing sepiolite-based hybrid hydrogel for hemostasis and wound healing.

The process of wound healing necessitates a specific environment, thus prompting extensive research into the utilization of hydrogels for this purpose. While numerous hydrogel structures have been investigated, the discovery of a self-healing hydrogel possessing favorable biocompatibility, exceptional mechanical properties, and effective hemostatic and antibacterial performance remains uncommon. In this work, a polyvinyl alcohol (PVA) hybrid hydrogel was meticulously designed through a simple reaction, wherein CuxO anchored sepiolite was incorporated into the hydrogel. The results indicate that introduction of sepiolite greatly improves the toughness, self-healing and adhesion properties of the PVA hydrogels. CuxO nanoparticles endow the hydrogels with excellent antibacterial performance towards Staphylococcus aureus and Escherichia coli. The application of hybrid hydrogels for fast hemostasis and wound healing are verified in vitro and in vivo with rat experiments. This work thereby demonstrates an effective strategy for designing biodegradable hemostatic and wound healing materials.

BNST GABAergic neurons modulate wakefulness over sleep and anesthesia.

The neural circuits underlying sleep-wakefulness and general anesthesia have not been fully investigated. The GABAergic neurons in the bed nucleus of the stria terminalis (BNST) play a critical role in stress and fear that relied on heightened arousal. Nevertheless, it remains unclear whether BNST GABAergic neurons are involved in the regulation of sleep-wakefulness and anesthesia. Here, using in vivo fiber photometry combined with electroencephalography, electromyography, and video recordings, we found that BNST GABAergic neurons exhibited arousal-state-dependent alterations, with high activities in both wakefulness and rapid-eye movement sleep, but suppressed during anesthesia. Optogenetic activation of these neurons could initiate and maintain wakefulness, and even induce arousal from anesthesia. However, chronic lesion of BNST GABAergic neurons altered spontaneous sleep-wakefulness architecture during the dark phase, but not induction and emergence from anesthesia. Furthermore, we also discovered that the BNST-ventral tegmental area pathway might participate in promoting wakefulness and reanimation from steady-state anesthesia. Collectively, our study explores new elements in neural circuit mechanisms underlying sleep-wakefulness and anesthesia, which may contribute to a more comprehensive understanding of consciousness and the development of innovative anesthetics.

Many-objective bi-level energy scheduling method for integrated energy stations based on power allocation strategy.

The integrated energy station of new energy vehicle hydrogenation/charging/power exchange is proposed, which also includes hydrogen production, hydrogen storage, electricity sales to users and the grid (WPIES). To address the efficiency of renewable energy use, this paper proposes a future value competition strategy for wind and photovoltaic (PV) allocation based on goal optimization (FVCS). In order to better realize the distribution of wind power/PV in the integrated energy station and improve the energy utilization efficiency of the integrated energy station, a two-layer optimization model of FVCS-WPIES is proposed, in which the upper layer model aims to maximize the expected income. The goals of the lower-level model are to maximize total profit, minimize battery losses, and minimize pollutant emissions. The model also considers the hydrogen power constraint and the upper-level model penalty. The comparison results show that the Pareto solution set is superior to the traditional model.

A Suture Technique for Ruptured Annulus Fibrosus Following Decompression Under Percutaneous Transforaminal Endoscopic Discectomy.

The suture technique for a ruptured annulus fibrosus (AF) under full-endoscopy remains challenging. Direct suturing of a ruptured annular tear after full decompression has been shown to decrease the recurrence rate of lumbar disc herniation during endoscopic surgery. Traditional suture operations under endoscopy involve only simple suturing of the ruptured AF. Due to the weak and poor quality of the AF tissue around the tear portal, using this area as needle insertion points during suturing may lead to insufficient tension and a low success rate of AF closure. Currently, there is no detailed technical illustration based on video for AF tear suturing under lumbar full-endoscopy. We innovatively propose a method of covering and suturing the AF tear by pulling up the posterior longitudinal ligament (PLL) under lumbar endoscopy and using three stitches (PLL-AF suture technique). The patient who received the novel suture technique achieved satisfactory results. Six months after the operation, lumbar MRI showed no evidence of recurrence in the outpatient clinic.

Circularly Polarized Organic Light-Emitting Diodes Based on Chiral Hole Transport Enantiomers.

The circularly polarized organic light-emitting diodes (CP-OLEDs) demonstrate promising application in 3D display due to the direct generation of circularly polarized electroluminescence (CPEL). But the chiral luminescence materials face challenges as intricated synthetic route, enantiomeric separation, etc. Herein, fresh CP-OLEDs are designed based on chiral hole transport material instead of chiral emitters. A pair of hole transport enantiomers (R/S-NPACZ) exhibit intense dissymmetry factors (|gPL|) about 5.0 × 10-3. With R/S-NPACZ as hole transport layers, CP-OLEDs are fabricated employing six achiral phosphorescence and thermally activated delayed fluorescence (TADF) materials with different wavelengths, in consistence with the generated CPEL spectra. The CP-OLEDs based on achiral red, green, and blue iridium(III) complexes exhibit external quantum efficiencies (EQEs) of 14.9%, 30.7%, and 14.1% with |gEL| factors of 8.8 × 10-4, 2.3 × 10-3, and 2.0 × 10-3, respectively. Moreover, the devices using achiral blue, blueish-green, and green TADF materials display EQEs of 24.1%, 17.9%, and 25.4% with |gEL| factors of 1.0 × 10-3, 3.6 × 10-3, and 2.2 × 10-3, respectively. As far as known, it is the first example of CP-OLEDs based on chiral hole transport materials, which act as the organic circularly polarizers and have potential to generate CPEL from achiral luminescence materials.

Altered expression of the Plexin-B2 system in tuberous sclerosis complex and focal cortical dysplasia IIb lesions.

Tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type IIb are the predominant causes of drug-refractory epilepsy in children. Dysmorphic neurons (DNs), giant cells (GCs), and balloon cells (BCs) are the most typical pathogenic profiles in cortical lesions of TSC and FCD IIb patients. However, mechanisms underlying the pathological processes of TSC and FCD IIb remain obscure. The Plexin-B2-Sema4C signalling pathway plays critical roles in neuronal morphogenesis and corticogenesis during the development of the central nervous system. However, the role of the Plexin-B2 system in the pathogenic process of TSC and FCD IIb has not been identified. In the present study, we investigated the expression and cell distribution characteristics of Plexin-B2 and Sema4C in TSC and FCD IIb lesions with molecular technologies. Our results showed that the mRNA and protein levels of Plexin-B2 expression were significantly increased both in TSC and FCD IIb lesions versus that in the control cortex. Notably, Plexin-B2 was also predominantly observed in GCs in TSC epileptic lesions and BCs in FCD IIb lesions. In contrast, the expression of Sema4C, the ligand of Plexin-B2, was significantly decreased in DNs, GCs, and BCs in TSC and FCD IIb epileptic lesions. Additionally, Plexin-B2 and Sema4C were expressed in astrocytes and microglia cells in TSC and FCD IIb lesions. Furthermore, the expression of Plexin-B2 was positively correlated with seizure frequency in TSC and FCD IIb patients. In conclusion, our results showed the Plexin-B2-Sema4C system was abnormally expressed in cortical lesions of TSC and FCD IIb patients, signifying that the Plexin-B2-Sema4C system may play a role in the pathogenic development of TSC and FCD IIb.

A Web-based Prediction Model for Early Death in Patients With Metastatic Triple-negative Breast Cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the absence of expression of estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2. This subtype of breast cancer is known for its high aggressiveness, high metastatic potential, tendency for recurrence, and poor prognosis. Patients with metastatic TNBC (mTNBC) have a poorer prognosis and a higher likelihood of early death (survival time ≤3 months). Therefore, the development of effective individualized survival prediction tools, such as prediction nomograms and web-based survival calculators, is of great importance for predicting the probability of early death in patients with metastatic TNBC. METHODS: Patients diagnosed with mTNBC in the Surveillance, Epidemiology, and End Results database between 2010 and 2015 were included in the model construction. Univariate and multivariate logistic regression analysis was performed to identify risk factors associated with early death in patients with mTNBC and predictive prognostic nomograms were constructed. The accuracy of the nomograms was verified using receiver operating characteristic curves, and GiViTi Calibration belt plots were used to evaluate the model consistency. The clinical applicability of the nomograms was evaluated using decision curve analysis. On the basis of the predictive prognostic nomograms, a network survival rate calculator was developed for individualized survival prediction in patients with mTNBC. RESULTS: A total of 2230 patients diagnosed with mTNBC were included in the Surveillance, Epidemiology, and End Results database for this study. After strict exclusion criteria, 1428 patients were found to be eligible for the study. All the patients were randomly divided into a training cohort and a validation cohort in a ratio of 7:3. Independent risk factors for mTNBC, including age, tumor size, brain metastasis, liver metastasis, surgery, and chemotherapy, were identified and integrated to construct the prediction nomogram and survival calculator. Results of receiver operating characteristic curves, calibration curves, and decision curve analysis curves from the training and validation cohort confirmed that the developed nomogram and web-based survival calculator in this study could accurately predict the probability of early death in patients with mTNBC. CONCLUSIONS: In this study, we developed a reliable prediction nomogram and web-based survival calculator for predicting the probability of early death in patients with mTNBC. These tools can assist clinical physicians in identifying high-risk patients and developing personalized treatment plans as early as possible.

Mapping the hotspots and future trends of electrical stimulation for peripheral nerve injury: A bibliometric analysis from 2002 to 2023.

Peripheral nerve injuries often result in severe personal and social burden, and even with surgical treatment, patients continue to have poor clinical outcomes. Over the past two decades, electrical stimulation has been shown to promote axonal regeneration and alleviate refractory neuropathic pain. The aim of this study was to analyse this field using a bibliometric approach. Literature was searched through Web of Science Core Collection (WOSCC) for the years 2002-2023. Literature analysis included: (1) Describing publication trends in the field. (2) Exploring collaborative network relationships. (3) Finding research advances and research hotspots in the field. (4) Summarizing research trends in the field. With the number of studies in this field still increasing, a total of 693 publications were included in the analysis. This field of research is interdisciplinary in nature. Research hotspots include peripheral nerve regeneration, the treatment of neuropathic pain, materials for nerve injury repair, and the restoration of sensory function in patients with peripheral nerve injury. Correspondingly, the development of nerve conduits and systems for peripheral nerve electrical stimulation, clinical trials of peripheral nerve electrical stimulation, and tactile recovery and movement for amputees have shown significant promise as future research trends in this field.