Chemical Design of Activatable Photoacoustic Probes for Precise Biomedical Applications.

Photoacoustic (PA) imaging technology, a three-dimensional hybrid imaging modality that integrates the advantage of optical and acoustic imaging, has great application prospects in molecular imaging due to its high imaging depth and resolution. To endow PA imaging with the ability for real-time molecular visualization and precise biomedical diagnosis, numerous activatable molecular PA probes which can specifically alter their PA intensities upon reacting with the targets or biological events of interest have been developed. This review highlights the recent developments of activatable PA probes for precise biomedical applications including molecular detection of the biotargets and imaging of the biological events. First, the generation mechanism of PA signals will be given, followed by a brief introduction to contrast agents used for PA probe design. Then we will particularly summarize the general design principles for the alteration of PA signals and activatable strategies for developing precise PA probes. Furthermore, we will give a detailed discussion of activatable PA probes in molecular detection and biomedical imaging applications in living systems. At last, the current challenges and outlooks of future PA probes will be discussed. We hope that this review will stimulate new ideas to explore the potentials of activatable PA probes for precise biomedical applications in the future.

Association of serum metal levels with type 2 diabetes: A prospective cohort and mediating effects of metabolites analysis in Chinese population.

Several studies have suggested an association between exposure to various metals and the onset of type 2 diabetes (T2D). However, the results vary across different studies. We aimed to investigate the associations between serum metal concentrations and the risk of developing T2D among 8734 participants using a prospective cohort study design. We utilized inductively coupled plasmamass spectrometry (ICP-MS) to assess the serum concentrations of 27 metals. Cox regression was applied to calculate the hazard ratios (HRs) for the associations between serum metal concentrations on the risk of developing T2D. Additionally, 196 incident T2D cases and 208 healthy control participants were randomly selected for serum metabolite measurement using an untargeted metabolomics approach to evaluate the mediating role of serum metabolite in the relationship between serum metal concentrations and the risk of developing T2D with a nested casecontrol study design. In the cohort study, after Bonferroni correction, the serum concentrations of zinc (Zn), mercury (Hg), and thallium (Tl) were positively associated with the risk of developing T2D, whereas the serum concentrations of manganese (Mn), molybdenum (Mo), barium (Ba), lutetium (Lu), and lead (Pb) were negatively associated with the risk of developing T2D. After adding these eight metals, the predictive ability increased significantly compared with that of the traditional clinical model (AUC: 0.791 vs. 0.772, P=8.85×10-5). In the nested casecontrol study, a machine learning analysis revealed that the serum concentrations of 14 out of 1579 detected metabolites were associated with the risk of developing T2D. According to generalized linear regression models, 7 of these metabolites were significantly associated with the serum concentrations of the identified metals. The mediation analysis showed that two metabolites (2-methyl-1,2-dihydrophthalazin-1-one and mestranol) mediated 46.81% and 58.70%, respectively, of the association between the serum Pb concentration and the risk of developing T2D. Our study suggested that serum Mn, Zn, Mo, Ba, Lu, Hg, Tl, and Pb were associated with T2D risk. Two metabolites mediated the associations between the serum Pb concentration and the risk of developing T2D.

Convolutional Neural Network-Based Pattern Recognition of Partial Discharge in High-Speed Electric-Multiple-Unit Cable Termination.

Partial discharge detection is considered a crucial technique for evaluating insulation performance and identifying defect types in cable terminals of high-speed electric multiple units (EMUs). In this study, terminal samples exhibiting four typical defects were prepared from high-speed EMUs. A cable discharge testing system, utilizing high-frequency current sensing, was developed to collect discharge signals, and datasets corresponding to these defects were established. This study proposes the use of the convolutional neural network (CNN) for the classification of discharge signals associated with specific defects, comparing this method with two existing neural network (NN)-based classification models that employ the back-propagation NN and the radial basis function NN, respectively. The comparative results demonstrate that the CNN-based model excels in accurately identifying signals from various defect types in the cable terminals of high-speed EMUs, surpassing the two existing NN-based classification models.

Short Chain Fatty Acids: Essential Weapons of Traditional Medicine in Treating Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal inflammatory disease, mainly including Crohn's disease (CD) and ulcerative colitis (UC). In recent years, the incidence and prevalence of IBD have been on the rise worldwide and have become a significant concern of health and a huge economic burden on patients. The occurrence and development of IBD involve a variety of pathogenic factors. The changes in short-chain fatty acids (SCFAs) are considered to be an important pathogenic mechanism of this disease. SCFAs are important metabolites in the intestinal microbial environment, which are closely involved in regulating immune, anti-tumor, and anti-inflammatory activities. Changes in metabolite levels can reflect the homeostasis of the intestinal microflora. Recent studies have shown that SCFAs provide energy for host cells and intestinal microflora, shape the intestinal environment, and regulate the immune system, thereby regulating intestinal physiology. SCFAs can effectively reduce the incidence of enteritis, cardiovascular disease, colon cancer, obesity, and diabetes, and also play an important role in maintaining the balance of energy metabolism (mainly glucose metabolism) and improving insulin tolerance. In recent years, many studies have shown that numerous decoctions and natural compounds of traditional Chinese medicine have shown promising therapeutic activities in multiple animal models of colitis and thus attracted increasing attention from scientists in the study of IBD treatment. Some of these traditional Chinese medicines or compounds can effectively alleviate colonic inflammation and clinical symptoms by regulating the generation of SCFAs. This study reviews the effects of various traditional Chinese medicines or bioactive substances on the production of SCFAs and their potential impacts on the severity of colonic inflammation. On this basis, we discussed the mechanism of SCFAs in regulating IBD-associated inflammation, as well as the related regulatory factors and signaling pathways. In addition, we provide our understanding of the limitations of current research and the prospects for future studies on the development of new IBD therapies by targeting SCFAs. This review may widen our understanding of the effect of traditional medicine from the view of SCFAs and their role in alleviating IBD animal models, thus contributing to the studies of IBD researchers.

[Clinical and genetic analysis of ten Chinese pedigrees affected with 7q11.23 duplication syndrome].

OBJECTIVE: To analyze the clinical and genetic characteristics of ten Chinese pedigrees affected with 7q11.23 duplication syndrome. METHODS: From December 2017 to January 2022, ten pedigrees diagnosed with 7q11.23 duplication syndrome at the First Affiliated Hospital of Zhengzhou University were enrolled as the study subjects. Clinical data of all subjects were collected, and some had subjected to copy number variation sequencing or single nucleotide polymorphism array to analyze the pattern of inheritance. RESULTS: The probands had included six fetuses and four adolescents. Four of the six prenatal cases showed abnormal ultrasound indicators, including three with soft indicators and one with abnormal fetal structural development. The clinical phenotype of the four adolescent cases had included mental retardation, delayed language development, and attention deficit hyperactivity disorder. The size of the copy number variations had ranged from 1.31 to 1.42 Mb, involving the classic region of 7q11.23 duplication syndrome. Of these, five cases had undergone parental origin testing, three cases were de novo, and two were hereditary. CONCLUSION: Individuals with 7q11.23 duplication syndrome may show substantial clinical phenotypic heterogeneity, hence the affected families should be provided with pre-pregnancy consultation and reproductive guidance.

"Four-In-One" Design of a Hemicyanine-Based Modular Scaffold for High-Contrast Activatable Molecular Afterglow Imaging.

Afterglow luminescence (long persistent luminescence) holds great potential for nonbackground molecular imaging. However, current afterglow probes are mainly nanoparticles, and afterglow imaging systems based on organic small molecules are still lacking and have rarely been reported. Moreover, the lack of reactive sites and a universal molecular scaffold makes it difficult to design activatable afterglow probes. To address these issues, this study reports a novel kind of hemicyanine-based molecule scaffolds with stimuli-responsive afterglow luminescence, which is dependent on an intramolecular cascade photoreaction between 1O2 and the afterglow molecule to store the photoenergy for delayed luminescence after light cessation. As a proof of concept, three modular activatable molecular afterglow probes (MAPs) with a "four-in-one" molecular design by integrating a stimuli-responsive unit, 1O2-generating unit, 1O2-capturing unit, and luminescent unit into one probe are customized for quantification and imaging of targets including pH, superoxide anions, and aminopeptidase. Notably, MAPs show higher sensitivity in afterglow imaging than in fluorescence imaging because the responsive unit simultaneously controls the initiation of fluorescence (S1 to S0) and 1O2 generation (S1 to T1). Finally, MAPs are applied for high-contrast afterglow imaging of drug-induced hepatotoxicity, which is poorly evaluated in clinics and drug discovery. By reporting the sequential occurrence of oxidative stress and upregulation of aminopeptidase, such activatable afterglow probes allow noninvasive imaging of hepatotoxicity earlier than the serological and histology manifestation, indicating their promise for early diagnosis of hepatotoxicity.

Cascaded subarray design and control method for power efficient, thermal crosstalk optimized optical phased array.

Thermo-optic phase shifters (TOPSs) are commonly used in large-scale silicon photonic integrated optical phased arrays (OPAs). However, fast-response TOPSs consume relatively high power; the elevated temperature floor in the dense region of the TOPSs introduces thermal crosstalk between optical paths, which undermines the control accuracy. We propose a combined method that involves subarray design in the optical power distribution network and array control method to predict, optimize, and redistribute the phase shifts and mitigates thermal crosstalk. Thermal simulations and an array control method for generic OPA models are discussed. A silicon photonic chip prototype of a 4 × 4 OPA with three-level cascaded subarrays is fabricated to demonstrate the proposed method. The experimental and statistical results show that the method effectively reduces the average total power consumption by 31%, the maximum local temperature by 18.4%, and the thermal crosstalk within the OPA.

The impact of frailty evaluation on the risk of venous thromboembolism in patients with hip fracture following surgery: a meta-analysis.

BACKGROUND: Frailty has been associated with a higher incidence of overall postoperative complications and mortality. However, the influence of frailty on the risk of venous thromboembolism (VTE) in patients with hip fracture following surgery remains unclear. We performed a meta-analysis to systematically evaluate the above association. METHODS: PubMed, Embase, Cochrane Library, Wanfang and CNKI were searched for relevant observational studies comparing the incidence of postoperative VTE in patients of hip fracture with and without frailty. Data collection, literature searching, and statistical analysis were conducted independently by two authors. Using a heterogeneity-incorporating random-effects model, the results were pooled. RESULTS: In this meta-analysis, 9509 patients from nine cohort studies were included. Pooled results showed that compared to those without frailty, patients with frailty at admission had a higher incidence of postoperative VTE (odds ratio [OR]: 2.59, 95% confidence interval [CI]: 1.25-5.39, p = 0.01; I2 = 66%). Subgroup analysis suggested the association between frailty and postoperative VTE was more remarkable in studies of patients with frailty prevalence < 50% (OR 6.28, 95% CI 3.31-11.90, p < 0.001; I2 = 8%) as compared to those ≥ 50% (OR 1.30, 95% CI 0.80-2.11, p = 0.28; I2 = 0%; p for subgroup difference < 0.001). Further meta-analyses showed that frailty at baseline was associated with a higher incidence of deep venous thrombosis (OR 3.15, 95% CI 1.33-7.47, p = 0.009; I2 = 59%), but not pulmonary embolism (OR 1.13, 95% CI 0.59-2.16, p = 0.72; I2 = 0%). CONCLUSION: Frailty is associated with a higher incidence of postoperative VTE in patients with hip fracture.

Thirty-year changes of the coastlines, wetlands, and ecosystem services in the Asia major deltas.

Coastal zones are usually composed of coastlines and coastal wetlands and are among the most productive and dynamic ecosystems. However, the deltas are seldom detected and compared in detail at the continental scale to investigate the spatiotemporal evolution of coastline migration and coastal wetlands. Here we detected and compared the spatiotemporal changes in coastlines, wetlands, and ecosystem services in major deltas in Asia, including the Yellow River Delta (YRD), Yangtze River Delta (YAD), Pearl River Delta (PRD), Red River Delta (RRD), Mekong River Delta (MERD), Chao Phraya River Delta (CPRD), Mahanadi River Delta (MARD), Krishna River Delta (KRD), and Indus River Delta (IRD). We used time series remote sensing images from 1990 to 2019 to derive coastline and wetland information for the nine coastal zones. The ecosystem service value coefficients were applied to explore the ecosystem services characteristics of wetland changes in coastal areas. We found that the coastlines of the deltas in the study area changed less in the bedrock and sandy coasts, while the coastlines in the silty delta coasts changed more from 1990 to 2019. The interannual dynamics of coastal wetland areas in nine major deltas over the nearly 30 years can be divided into three periods: decreasing variability (1990-2005), increasing variability (2005-2015), and increasing volatility (2015-2019). Ecosystem services had an overall downward trend. These findings complement the official database of coastal planning and have substantial guiding implications for adjusting coastal management regulation policies.

A meta-analysis result: Uneven influences of season, geo-spatial scale and latitude on relationship between meteorological factors and the COVID-19 transmission.

Meteorological factors have been confirmed to affect the COVID-19 transmission, but current studied conclusions varied greatly. The underlying causes of the variance remain unclear. Here, we proposed two scientific questions: (1) whether meteorological factors have a consistent influence on virus transmission after combining all the data from the studies; (2) whether the impact of meteorological factors on the COVID-19 transmission can be influenced by season, geospatial scale and latitude. We employed a meta-analysis to address these two questions using results from 2813 published articles. Our results showed that, the influence of meteorological factors on the newly-confirmed COVID-19 cases varied greatly among existing studies, and no consistent conclusion can be drawn. After grouping outbreak time into cold and warm seasons, we found daily maximum and daily minimum temperatures have significant positive influences on the newly-confirmed COVID-19 cases in cold season, while significant negative influences in warm season. After dividing the scope of the outbreak into national and urban scales, relative humidity significantly inhibited the COVID-19 transmission at the national scale, but no effect on the urban scale. The negative impact of relative humidity, and the positive impacts of maximum temperatures and wind speed on the newly-confirmed COVID-19 cases increased with latitude. The relationship of maximum and minimum temperatures with the newly-confirmed COVID-19 cases were more susceptible to season, while relative humidity's relationship was more affected by latitude and geospatial scale. Our results suggested that relationship between meteorological factors and the COVID-19 transmission can be affected by season, geospatial scale and latitude. A rise in temperature would promote virus transmission in cold seasons. We suggested that the formulation and implementation of epidemic prevention and control should mainly refer to studies at the urban scale. The control measures should be developed according to local meteorological properties for individual city.