The Enhanced Photoluminescence Properties of Carbon Dots Derived from Glucose: The Effect of Natural Oxidation.

The investigation of the fluorescence mechanism of carbon dots (CDs) has attracted significant attention, particularly the role of the oxygen-containing groups. Dual-CDs exhibiting blue and green emissions are synthesized from glucose via a simple ultrasonic treatment, and the oxidation degree of the CDs is softly modified through a slow natural oxidation approach, which is in stark contrast to that aggressively altering CDs' surface configurations through chemical oxidation methods. It is interesting to find that the intensity of the blue fluorescence gradually increases, eventually becoming the dominant emission after prolonging the oxidation periods, with the quantum yield (QY) of the CDs being enhanced from ~0.61% to ~4.26%. Combining the microstructure characterizations, optical measurements, and ultrafiltration experiments, we hypothesize that the blue emission could be ascribed to the surface states induced by the C-O and C=O groups, while the green luminescence may originate from the deep energy levels associated with the O-C=O groups. The distinct emission states and energy distributions could result in the blue and the green luminescence exhibiting distinct excitation and emission behaviors. Our findings could provide new insights into the fluorescence mechanism of CDs.

Study on compaction characteristics and mechanical model of dry crushing filling material under lateral confinement condition.

The compaction characteristics and bearing capacity of dry filling materials in goaf have a significant influence on stope control and surface stability. Through acoustic emission monitoring and mechanical model analysis, a series of confined compression tests were conducted on crushed waste with varying particle sizes and Talbot coefficients. The deformation, fragmentation, and acoustic emission characteristics under corresponding working conditions were determined. The results indicate that the stress-strain curves of crushed stone with different particle sizes and Talbot coefficients exhibit similar nonlinear behavior during confined compression. However, the strain response varies with changing stress levels. By analyzing the slope change rate of the stress-strain curve, the lateral uniaxial compression process of waste rock can be divided into three deformation stages: rapid compression, stable crushing, and slow compaction. The compressive deformation characteristics of gravel differ based on particle size and Talbot coefficient. Specimens with a higher Talbot coefficient demonstrate stronger compressive resistance and weaker deformation resistance during initial compaction loading. Notably, the internal pressure structure strength is influenced by factors such as maximum particle size D, grading coefficient n, and particle size distribution continuity, rather than solely by the proportion of large particles. The evolution of acoustic emission signals and energy-time curve during waste rock confined axial compression synchronizes with the compaction process. Overall, compaction plays a critical role in maintaining the stability of goaf in dry crushed waste filling.

Another string to your bow: machine learning prediction of the pharmacokinetic properties of small molecules.

INTRODUCTION: Prediction of pharmacokinetic (PK) properties is crucial for drug discovery and development. Machine-learning (ML) models, which use statistical pattern recognition to learn correlations between input features (such as chemical structures) and target variables (such as PK parameters), are being increasingly used for this purpose. To embed ML models for PK prediction into workflows and to guide future development, a solid understanding of their applicability, advantages, limitations, and synergies with other approaches is necessary. AREAS COVERED: This narrative review discusses the design and application of ML models to predict PK parameters of small molecules, especially in light of established approaches including in vitro-in vivo extrapolation (IVIVE) and physiologically based pharmacokinetic (PBPK) models. The authors illustrate scenarios in which the three approaches are used and emphasize how they enhance and complement each other. In particular, they highlight achievements, the state of the art and potentials of applying machine learning for PK prediction through a comphrehensive literature review. EXPERT OPINION: ML models, when carefully crafted, regularly updated, and appropriately used, empower users to prioritize molecules with favorable PK properties. Informed practitioners can leverage these models to improve the efficiency of drug discovery and development process.

Optical coherence tomography-guided Brillouin microscopy highlights regional tissue stiffness differences during anterior neural tube closure in the Mthfd1l murine mutant.

Neurulation is a highly synchronized biomechanical process leading to the formation of the brain and spinal cord, and its failure leads to neural tube defects (NTDs). Although we are rapidly learning the genetic mechanisms underlying NTDs, the biomechanical aspects are largely unknown. To understand the correlation between NTDs and tissue stiffness during neural tube closure (NTC), we imaged an NTD murine model using optical coherence tomography (OCT), Brillouin microscopy and confocal fluorescence microscopy. Here, we associate structural information from OCT with local stiffness from the Brillouin signal of embryos undergoing neurulation. The stiffness of neuroepithelial tissues in Mthfd1l null embryos was significantly lower than that of wild-type embryos. Additionally, exogenous formate supplementation improved tissue stiffness and gross embryonic morphology in nullizygous and heterozygous embryos. Our results demonstrate the significance of proper tissue stiffness in normal NTC and pave the way for future studies on the mechanobiology of normal and abnormal embryonic development.

Utility of somatosensory- and motor-evoked potential change thresholds in surgical treatment for thoracic spinal stenosis based on different pathologies.

BACKGROUND CONTEXT: Thoracic spinal stenosis (TSS) is secondary to different pathologies that differ in clinical characteristics and surgical outcomes. PURPOSE: This study aimed to determine the optimal warning thresholds for combined somatosensory-evoked potentials (SSEP) and motor-evoked potentials (MEP) for predicting postoperative neurological deterioration in surgical treatment for TSS based on different pathologies. Additionally, we explored the correlation between SSEP/MEP monitoring and postoperative spinal neurological function. STUDY SETTING: Retrospective study. PATIENT SAMPLE: Two hundred and five patients. OUTCOME MEASURES: We obtained perioperative modified Japanese Orthopedic Association (mJOA) scores to assess spinal neurological function. METHODS: The data collected in this study included demographic data, intraoperative neurophysiological monitoring (IONM) signals, and perioperative neurological function assessments. To determine the optimal IONM warning threshold, a receiver operating characteristic (ROC) curve was used. Additionally, Pearson correlation analysis was conducted to determine the correlation between IONM signals and clinical neurological conditions. RESULTS: A total of 205 consecutive patients were eligible. Forty-one patients had thoracic disc herniation (TDH), 14 had ossification of the posterior longitudinal ligament (OPLL), 124 had ossification of the ligamentum flavum (OLF), and 26 had OPLL+OLF. The mean mJOA scores before surgery and 3 months after surgery were 7.0 and 7.9, respectively, resulting in a mean mJOA recovery rate (RR) of 23.1%. The average postoperative mJOA RRs for patients with TDH, OPLL, OLF, and OPLL+OLF were 24.8%, 10.4%, 26.8%, and 11.2%, respectively. Patients with OPLL+OLF exhibited a more stringent threshold for IONM changes. This included a lower amplitude cutoff value (a decrease of 49.0% in the SSEP amplitude and 57.5% in the MEP amplitude for short-term prediction) and a shorter duration of waveform change (19.5 minutes for SSEP and 22.5 minutes for MEP for short-term prediction). On the other hand, patients with TDH had more lenient IONM warning criteria (a decrease of 49.0% in SSEP amplitude and 77.5% in MEP amplitude for short-term prediction; durations of change of 25.5 minutes for SSEP and 32.5 minutes for MEP). However, OPLL patients or OLF patients had moderate and similar IONM warning thresholds. Additionally, there was a stronger correlation between the SSEP amplitude variability ratio and the JOA RR in OPLL+OLF patients, while the correlation was stronger between the MEP amplitude variability ratio and the JOA RR for the other three TSS pathologies. CONCLUSIONS: Optimal IONM change criteria for prediction vary depending on different TSS pathologies. The optimal monitoring strategy for prediction varies depending on TSS pathologies.

Wettability and Bactericidal Properties of Bioinspired ZnO Nanopillar Surfaces.

Nanomaterials of zinc oxide (ZnO) exhibit antibacterial activities under ambient illumination that result in cell membrane permeability and disorganization, representing an important opportunity for health-related applications. However, the development of antibiofouling surfaces incorporating ZnO nanomaterials has remained limited. In this work, we fabricate superhydrophobic surfaces based on ZnO nanopillars. Water droplets on these superhydrophobic surfaces exhibit small contact angle hysteresis (within 2-3°) and a minimal tilting angle of 1°. Further, falling droplets bounce off when impacting the superhydrophobic ZnO surfaces with a range of Weber numbers (8-46), demonstrating that the surface facilitates a robust Cassie-Baxter wetting state. In addition, the antibiofouling efficacy of the surfaces has been established against model pathogenic Gram-positive bacteria Staphylococcus aureus (S. aureus) and Gram-negative bacteria Escherichia coli (E. coli). No viable colonies of E. coli were recoverable on the superhydrophobic surfaces of ZnO nanopillars incubated with cultured bacterial solutions for 18 h. Further, our tests demonstrate a substantial reduction in the quantity of S. aureus that attached to the superhydrophobic ZnO nanopillars. Thus, the superhydrophobic ZnO surfaces offer a viable design of antibiofouling materials that do not require additional UV illumination or antimicrobial agents.

Ultrasound-guided versus fluoroscopy-guided lumbar selective nerve root block: a retrospective comparative study.

The purpose of this study is to compare the accuracy and effectiveness of ultrasound-guided and fluoroscopy-guided lumbar selective nerve root block (SNRB), and to explore the feasibility of ultrasound-guided methods. This retrospective study included patients with lumbar radicular pain who underwent ultrasound-guided and fluoroscopy-guided selective nerve root block at Honghui Hospital Affiliated to Xi'an Jiaotong University from August 2020 to August 2022. Patients were divided into U-SNRB group and F-SNRB group according to ultrasound-guided or fluoroscopy-guided selective nerve root block. There were 43 patients in U-SNRB group and 20 patients in F-SNRB group. The pain visual analogue scale (VAS) scores, Japanese Orthopaedic Association (JOA) scores, related indexes and complications were recorded and compared between the two groups before, 30 min, 1 month and 6 months after block. To evaluate the feasibility, accuracy and effectiveness of ultrasound-guided selective nerve root block. There were no complications in the process of selective nerve root block in both groups. The operating time and the times of closing needle angle adjustment in U-SNRB group were better than those in F-SNRB group, and the difference was statistically significant (P < 0.05). The VAS score and JOA score of patients in the two groups were significantly improved 30 min after block, 1 month and 6 months after block, and the difference was statistically significant (P < 0.05). There was no significant difference between the two groups (P > 0.05). The accuracy of ultrasound-guided selective nerve root block and the degree of pain relief of patients were similar to those of fluoroscopy guidance, but the operation time and needle angle adjustment times were significantly less than that of fluoroscopy, and could effectively reduce radiation exposure. Therefore, it can be used as a better way to guide for choice.

Effects of extreme precipitation on bacterial communities and bioaerosol composition: Dispersion in urban outdoor environments and health risks.

Concerns about contaminants dispersed by seasonal precipitation have grown due to their potential hazards to outdoor environments and human health. However, studies on the crucial environmental factors influencing dispersion changes in bacterial communities are limited. This research adopted four-season in situ monitoring and sequencing techniques to examine the regional distribution profiles of bioaerosols, bacterial communities, and risks associated with extreme snowfall versus rainfall events in two monsoon cities. In the early-hours of winter snowfall, airborne cultivable bioaerosol concentrations were 4.1 times higher than the reference exposure limit (500 CFU/m3). The concentration of ambient particles (2.5 µm) exceeded 24,910 particles/L (97 µg/m3), positively correlating with the prevalence of cultivable bioaerosols. These bioaerosols contained cultivable bacterial species such as pathogenic Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Escherichia coli. Bioaerosol concentrations increased by 53.0% during 50-mm snow extremes. Taxonomic analysis revealed that Pseudomonas, Staphylococcus, and Veillonella were the most abundant bacterial taxa in the initial snowmelt samples during winter precipitation. However, their abundance decreased by 87.6% as snowing continued (24 h). Reduced water base cation concentration also led to a 1.15-fold increase in the Shannon index, indicating a similar yet heightened bacterial diversity. Seasonally, Pedobacter and Massilia showed higher relative abundance (25% and 18%, respectively), presenting increased bacterial transmission to the soil. Furthermore, Pseudomonas was identified in 60% of spring snowstorm samples, suggesting long-distance dispersal of pathogenic bacteria. When these atmospheric aerosol particles carrying biological entities (0.65-1.1 µm) penetrated human alveoli, the calculated hazard ratio was 0.55, which as observed in inhalation exposures. Consequently, this study underscores the risk of seasonal precipitation-enhanced ambient bacterial transmission.

A randomized, double-blind phase 1b study evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of the NLRP3 inhibitor selnoflast in patients with moderate to severe active ulcerative colitis.

BACKGROUND: The NLRP3 inflammasome drives release of pro-inflammatory cytokines including interleukin (IL)-1ß and IL-18 and is a potential target for ulcerative colitis (UC). Selnoflast (RO7486967) is an orally active, potent, selective and reversible small molecule NLRP3 inhibitor. We conducted a randomized, placebo-controlled Phase 1b study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of selnoflast. METHODS: Nineteen adults with previous diagnosis of UC and current active moderate to severe disease were randomized 2:1 to selnoflast or placebo for 7 days. A dose of 450 mg QD (once daily) was selected to achieve 90% IL-1ß inhibition in plasma and colon tissue. Consecutive blood, sigmoid colon biopsies and stool samples were analyzed for a variety of PD markers. Safety and PK were also evaluated. RESULTS: Selnoflast was well-tolerated. Plasma concentrations increased rapidly after oral administration, reaching Tmax 1 h post-dose. Mean plasma concentrations stayed above the IL-1ß IC90 level throughout the dosing interval (mean Ctrough on Day 1 and Day 5: 2.55 µg/mL and 2.66 µg/mL, respectively). At steady state, post-dose selnoflast concentrations in sigmoid colon (5-20 µg/g) were above the IC90 . Production of IL-1ß was reduced in whole blood following ex vivo stimulation with lipopolysaccharide (LPS) (in the selnoflast arm). No changes were observed in plasma IL-18 levels. There were no meaningful differences in the expression of an IL-1-related gene signature in sigmoid colon tissue, and no differences in the expression of stool biomarkers. CONCLUSIONS: Selnoflast was safe and well-tolerated. Selnoflast 450 mg QD achieved plasma and tissue exposure predicted to maintain IL-1ß IC90 over the dosing interval. However, PD biomarker results showed no robust differences between treatment arms, suggesting no major therapeutic effects are to be expected in UC. The limitations of this study are its small sample size and indirect assessment of the effect on IL-1ß in tissue. TRIAL REGISTRATION: ISRCTN16847938.

Monitoring the Mechanical Evolution of Tissue During Neural Tube Closure of Chick Embryo.

Neural tube closure (NTC) is a critical process during embryonic development. Failure in this process can lead to neural tube defects, causing congenital malformations or even mortality. NTC involves a series of mechanisms on genetic, molecular, and mechanical levels. While mechanical regulation has become an increasingly attractive topic in recent years, it remains largely unexplored due to the lack of suitable technology for conducting mechanical testing of 3D embryonic tissue in situ. In response, we have developed a protocol for quantifying the mechanical properties of chicken embryonic tissue in a non-contact and non-invasive manner. This is achieved by integrating a confocal Brillouin microscope with an on-stage incubation system. To probe tissue mechanics, a pre-cultured embryo is collected and transferred to an on-stage incubator for ex ovo culture. Simultaneously, the mechanical images of the neural plate tissue are acquired by the Brillouin microscope at different time points during development. This protocol includes detailed descriptions of sample preparation, the implementation of Brillouin microscopy experiments, and data post-processing and analysis. By following this protocol, researchers can study the mechanical evolution of embryonic tissue during development longitudinally.

KDELR2 as a diagnostic and prognostic biomarker of bladder urothelial carcinoma and its correlation with immune infiltration.

KDELR2 has been reported as a promotive factor for the genesis and progression of several malignancies. However, it is uncertain how it affects bladder urothelial carcinoma (BLCA). Using data extracted from online databases, an enhanced expression of KDELR2 in BLCA tissues was verified. Overexpression of KDELR2 was correlated with advanced clinicopathologic characteristics and unfavourable prognosis of BLCA. Receiver operating characteristic analysis highlighted the potential diagnostic value of KDELR2. Univariate and multivariate logistic regression analyses further revealed the predictive effect of KDELR2 for the prognosis of BLCA. KDELR2 was primarily enriched in biological functions related to organization of the extracellular matrix. TIMER, ssGSEA and GEPIA analyses suggested that KDELR2 expression is positively related to the infiltration of macrophages, Th2 cells and neutrophils. Finally, knocking-down of KDELR2 in T24 cells resulted in reduced proliferation, migration and macrophages recruitment. These results suggest that KDELR2 overexpression is an indicator for poor prognosis of BLCA and it has the potential to be employed as an immunotherapy target for BLCA.

A Novel Role of Connective Tissue Growth Factor in the Regulation of the Epithelial Phenotype.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is a biological process where epithelial cells lose their adhesive properties and gain invasive, metastatic, and mesenchymal properties. Maintaining the balance between the epithelial and mesenchymal stage is essential for tissue homeostasis. Many of the genes promoting mesenchymal transformation have been identified; however, our understanding of the genes responsible for maintaining the epithelial phenotype is limited. Our objective was to identify the genes responsible for maintaining the epithelial phenotype and inhibiting EMT. METHODS: RNA seq was performed using an vitro model of EMT. CTGF expression was determined via qPCR and Western blot analysis. The knockout of CTGF was completed using the CTGF sgRNA CRISPR/CAS9. The tumorigenic potential was determined using NCG mice. RESULTS: The knockout of CTGF in epithelial ovarian cancer cells leads to the acquisition of functional characteristics associated with the mesenchymal phenotype such as anoikis resistance, cytoskeleton remodeling, increased cell stiffness, and the acquisition of invasion and tumorigenic capacity. CONCLUSIONS: We identified CTGF is an important regulator of the epithelial phenotype, and its loss is associated with the early cellular modifications required for EMT. We describe a novel role for CTGF, regulating cytoskeleton and the extracellular matrix interactions necessary for the conservation of epithelial structure and function. These findings provide a new window into understanding the early stages of mesenchymal transformation.

Causal inference in drug discovery and development.

To discover new drugs is to seek and to prove causality. As an emerging approach leveraging human knowledge and creativity, data, and machine intelligence, causal inference holds the promise of reducing cognitive bias and improving decision-making in drug discovery. Although it has been applied across the value chain, the concepts and practice of causal inference remain obscure to many practitioners. This article offers a nontechnical introduction to causal inference, reviews its recent applications, and discusses opportunities and challenges of adopting the causal language in drug discovery and development.

Versatile multimodal modality based on Brillouin light scattering and the photoacoustic effect.

Multimodal optical techniques are useful for the comprehensive characterization of material properties. In this work, we developed a new, to the best of our knowledge, multimodal technology that can simultaneously measure a subset of mechanical, optical, and acoustical properties of the sample and is based on the integration of Brillouin (Br) and photoacoustic (PA) microscopy. The proposed technique can acquire co-registered Br and PA signals from the sample. Importantly, using synergistic measurements of the speed of sound and Brillouin shift, the modality offers a new approach to quantifying the optical refractive index, which is a fundamental property of a material and is not accessible by either technique individually. As a proof of concept, we demonstrated the feasibility of integrating the two modalities and acquired the colocalized Br and time-resolved PA signals in a synthetic phantom made out of kerosene and CuSO4 aqueous solution. In addition, we measured the refractive index values of saline solutions and validated the result. Comparison with previously reported data showed a relative error of 0.3%. This further allowed us to directly quantify the longitudinal modulus of the sample with the colocalized Brillouin shift. While the scope of the current work is limited to introducing the combined Br-PA setup for the first time, we envision that this multimodal modality could open a new path for the multi-parametric analysis of material properties.

Non-contact and label-free biomechanical imaging: Stimulated Brillouin microscopy and beyond.

Brillouin microscopy based on spontaneous Brillouin scattering has emerged as a unique elastography technique because of its merit of non-contact, label-free, and high-resolution mechanical imaging of biological cell and tissue. Recently, several new optical modalities based on stimulated Brillouin scattering have been developed for biomechanical research. As the scattering efficiency of the stimulated process is much higher than its counterpart in the spontaneous process, stimulated Brillouin-based methods have the potential to significantly improve the speed and spectral resolution of existing Brillouin microscopy. Here, we review the ongoing technological advancements of three methods, including continuous wave stimulated Brillouin microscopy, impulsive stimulated Brillouin microscopy, and laser-induced picosecond ultrasonics. We describe the physical principle, the representative instrumentation, and biological application of each method. We further discuss the current limitations as well as the challenges for translating these methods into a visible biomedical instrument for biophysics and mechanobiology.

The effects of environmental information disclosure on stock price synchronicity in China.

Environmental information disclosure has attracted the attention of the capital market because it can convey corporate characteristic information. But there needs to be direct evidence that environmental information disclosure can improve the market's overall efficiency. This study examines whether corporate environmental information disclosure can improve the information efficiency of the capital market. This study takes Chinese listed companies from 2008 to 2021 as samples, constructs a panel fixed effect model, and adopts multiple linear, instrumental variable method and Heckman sample selection model. We find that the disclosure of environmental information in the Chinese market reduces the information efficiency of the capital market represented by the synchronicity of stock prices. The reason is that the information after greenwashing by enterprises needs to be of better quality and more obscure, which disrupts market information. Environmental information disclosure by enterprises prone to greenwashing significantly affects stock price synchronicity, such as low institutional ownership, non-state-owned, growth, and manufacturing firms. Finally, this paper discusses the impact mechanism and confirms that stock liquidity and analyst coverage are the two paths through which environmental information disclosure impacts stock price synchronicity. This study is significant in encouraging the government to strengthen market supervision, promoting enterprises to disclose high-quality environmental information, and improving the pricing efficiency of the capital market.