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Light has profoundly impacted modern medicine and healthcare, with numerous luminescent agents and imaging techniques currently being used to assess health and treat diseases. As an emerging concept in luminescence, aggregation-induced emission (AIE) has shown great potential in biological applications due to its advantages in terms of brightness, biocompatibility, photostability, and positive correlation with concentration. This review provides a comprehensive summary of AIE luminogens applied in imaging of biological structure and dynamic physiological processes, disease diagnosis and treatment, and detection and monitoring of specific analytes, followed by representative works. Discussions on critical issues and perspectives on future directions are also included. This review aims to stimulate the interest of researchers from different fields, including chemistry, biology, materials science, medicine, etc., thus promoting the development of AIE in the fields of life and health.

ABSTRACTThe increasing antibiotic resistance poses a significant global health challenge, threatening our ability to combat infectious diseases. The phenomenon of collateral sensitivity, whereby resistance to one antibiotic is accompanied by increased sensitivity to another, offers potential avenues for novel therapeutic interventions against infections unresponsive to classical treatments. In this study, we elucidate the emergence of tobramycin (TOB)-resistant small colony variants (SCVs) due to mutations in the hemL gene, which render S. Typhimurium more susceptible to nitrofurantoin (NIT). Mechanistic studies demonstrate that the collateral sensitivity in TOB-resistant S. Typhimurium SCVs primarily stems from disruptions in haem biosynthesis. This leads to dysfunction in the electron transport chain (ETC) and redox imbalance, ultimately inducing lethal accumulation of reactive oxygen species (ROS). Additionally, the upregulation of nfsA/B expressions facilitates the conversion of NIT prodrug into its active form, promoting ROS-mediated bacterial killing and contributing to this collateral sensitivity pattern. Importantly, alternative NIT therapy demonstrates a significant reduction of bacterial load by more than 2.24-log10 cfu/g in the murine thigh infection and colitis models. Our findings corroborate the collateral sensitivity of S. Typhimurium to nitrofurans as a consequence of evolving resistance to aminoglycosides. This provides a promising approach for treating infections due to aminoglycoside-resistant strains.

ABSTRACT The dissemination of antibiotic resistance genes (ARGs) through plasmids is a major mechanism for the development of bacterial antimicrobial resistance. The adaptation and evolution mechanisms of multidrug-resistant (MDR) plasmids with their hosts are not fully understood. Herein, we conducted experimental evolution of a 244 kb MDR plasmid (pJXP9) under various conditions including no antibiotics and mono- or combinational drug treatments of colistin (CS), cefotaxime (CTX), and ciprofloxacin (CIP). Our results showed that long-term with or without positive selections for pJXP9, spanning approximately 600 generations, led to modifications of the plasmid-encoded MDR and conjugative transfer regions. These modifications could mitigate the fitness cost of plasmid carriage and enhance plasmid maintenance. The extent of plasmid modifications and the evolution of plasmid-encoded antibiotic resistance depended on treatment type, particularly the drug class and duration of exposure. Interestingly, prolonged exposure to mono- and combinational drugs of CS and CIP resulted in a substantial loss of the plasmid-encoded MDR region and antibiotic resistance, comparable to the selection condition without antibiotic. By contrast, combinational treatment with CTX contributed to the maintenance of the MDR region over a long period of time. Furthermore, drug selection was able to maintain and even amplify the corresponding plasmid-encoded ARGs, with co-selection of ARGs in the adjacent regions. In addition, parallel mutations in chromosomal arcA were also found to be associated with pJXP9 plasmid carriage among endpoint-evolved clones from diverse treatments. Meanwhile, arcA deletion improved the persistence of pJXP9 plasmid without drugs. Overall, our findings indicated that plasmid-borne MDR region deletion and chromosomal arcA inactivation mutation jointly contributed to co-adaptation and co-evolution between MDR IncHI2 plasmid and Salmonella Typhimurium under different drug selection pressure.IMPORTANCEThe plasmid-mediated dissemination of antibiotic resistance genes has become a significant concern for human health, even though the carriage of multidrug-resistant (MDR) plasmids is frequently associated with fitness costs for the bacterial host. However, the mechanisms by which MDR plasmids and bacterial pairs evolve plasmid-mediated antibiotic resistance in the presence of antibiotic selections are not fully understood. Herein, we conducted an experimental evolution of a large multidrug-resistant plasmid in a Salmonella enterica Typhimurium host under single and combinatorial drug selection pressures. Our results show the adaptive evolution of plasmid-encoded antibiotic resistance through alterations of the MDR region in the plasmid, in particular substantial loss of the MDR region, in response to different positive selections, especially mono- and combinational drugs of colistin and ciprofloxacin. In addition, strong parallel mutations in chromosomal arcA were associated with pJXP9 carriage in Salmonella Typhimurium from diverse treatments. Our results thus highlight promoting the loss of the plasmid’s MDR region could offer an alternative approach for combating plasmid-encoded antibiotic resistance.

ABSTRACT Salmonella 4,[5],12:i:-, a monophasic variant of Salmonella Typhimurium, has emerged as a global cause of multidrug-resistant salmonellosis and has become endemic in many developing and developed countries, especially in China. Here, we have sequenced 352 clinical isolates in Guangdong, China, during 2009–2019 and performed a large-scale collection of Salmonella 4,[5],12:i:- with whole genome sequencing (WGS) data across the globe, to better understand the population structure, antimicrobial resistance (AMR) genomic characterization, and transmission routes of Salmonella 4,[5],12:i:- across Guangdong. Salmonella 4,[5],12:i:- strains showed broad genetic diversity; Guangdong isolates were found to be widely distributed among the global lineages. Of note, we identified the formation of a novel Guangdong clade (Bayesian analysis of population structure lineage 1 [BAPS1]) genetically diversified from the global isolates and likely emerged around 1990s. BAPS1 exhibits unique genomic features, including large pan-genome, decreased ciprofloxacin susceptibility due to mutation in gyrA and carriage of plasmid-mediated quinolone resistance (PMQR) genes, and the multidrug-resistant IncHI2 plasmid. Furthermore, high genetic similarity was found between strains collected from Guangdong, Europe, and North America, indicating the association with multiple introductions from overseas. These results suggested that global dissemination and local clonal expansion simultaneously occurred in Guangdong, China, and horizontally acquired resistance to first-line and last-line antimicrobials at local level, underlying emergences of extensive drug and pan-drug resistance. Our findings have increased the knowledge of global and local epidemics of Salmonella 4,[5],12:i:- in Guangdong, China, and provided a comprehensive baseline data set essential for future molecular surveillance.IMPORTANCESalmonella 4,[5],12:i:- has been regarded as the predominant pandemic serotype causing diarrheal diseases globally, while multidrug resistance (MDR) constitutes great public health concerns. This study provided a detailed and comprehensive genome-scale analysis of this important Salmonella serovar in the past decade in Guangdong, China. Our results revealed the complexity of two distinct transmission modes, namely global transmission and local expansion, circulating in Guangdong over a decade. Using phylogeography models, the origin of Salmonella 4,[5],12:i:- was predicted from two aspects, year and country, that is, Salmonella 4,[5],12:i:- emerged in 1983, and was introduced from the UK, and subsequently differentiated into the local endemic lineage circa 1991. Additionally, based on the pan-genome analysis, it was found that the gene accumulation rate in local endemic BAPS 1 lineage was higher than in other lineages, and the horizontal transmission of MDR IncHI2 plasmid associated with high resistance played a major role, which showed the potential threat to public health.

Currently, servers store information from different sources and file types, which are then retrieved via electronic Information Management Systems (e-IMS), with Smart serving as an effective prototype system. Association rule testing and collaborative filtering are implemented to develop a Recommendation System (RS) for Mobile Application-based Official Document Management and Information Retrieval Systems (MA-ODM-IRS) that utilizes data structure and propensities to develop unique recommendations for common users. Reliable and accurate RS, which employs Machine Learning (ML)-based sentiment analysis to classify recommendations and novel performance metrics for target Information Retrieval (IF) from evaluation DMSs, enhances user trust. A recovery method significantly reduces data loss hazards and improves test case procedures for searching in IR, testing Mean Reciprocal Rank (MRR), Average Precision (AP), and retrieved document percentages. It recommends the novel MA-ODM-IRS and discusses the three experimental system iterations. A 0.75% reciprocal rank is better achieved by optimizing the MABIRS discovery process for users. Identifying feasible ideas, designing and implementing testing processes employing UML tools, and assessing the system gave the participants 98.19% acceptance.

Abstract Background Obstructive sleep apnea (OSA) is a globally prevalent disease with a complex diagnostic method. Severe OSA is associated with multi-system dysfunction. We aimed to develop an interpretable machine learning (ML) model for predicting the risk of severe OSA and analyzing the risk factors based on clinical characteristics and questionnaires. Methods This was a retrospective study comprising 1656 subjects who presented and underwent polysomnography (PSG) between 2018 and 2021. A total of 23 variables were included, and after univariate analysis, 15 variables were selected for further preprocessing. Six types of classification models were used to evaluate the ability to predict severe OSA, namely logistic regression (LR), gradient boosting machine (GBM), extreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), bootstrapped aggregating (Bagging), and multilayer perceptron (MLP). All models used the area under the receiver operating characteristic curve (AUC) was calculated as the performance metric. We also drew SHapley Additive exPlanations (SHAP) plots to interpret predictive results and to analyze the relative importance of risk factors. An online calculator was developed to estimate the risk of severe OSA in individuals. Results Among the enrolled subjects, 61.47% (1018/1656) were diagnosed with severe OSA. Multivariate LR analysis showed that 10 of 23 variables were independent risk factors for severe OSA. The GBM model showed the best performance (AUC = 0.857, accuracy = 0.766, sensitivity = 0.798, specificity = 0.734). An online calculator was developed to estimate the risk of severe OSA based on the GBM model. Finally, waist circumference, neck circumference, the Epworth Sleepiness Scale, age, and the Berlin questionnaire were revealed by the SHAP plot as the top five critical variables contributing to the diagnosis of severe OSA. Additionally, two typical cases were analyzed to interpret the contribution of each variable to the outcome prediction in a single patient. Conclusions We established six risk prediction models for severe OSA using ML algorithms. Among them, the GBM model performed best. The model facilitates individualized assessment and further clinical strategies for patients with suspected severe OSA. This will help to identify patients with severe OSA as early as possible and ensure their timely treatment. Trial registration Retrospectively registered.

Abstract Background Hemifacial macrosomia (HFM, OMIM 164210) is a complex and highly heterogeneous disease. FORKHEAD BOX I3 (FOXI3) is a susceptibility gene for HFM, and mice with loss of function of Foxi3 did exhibit a phenotype similar to craniofacial dysmorphism. However, the specific pathogenesis of HFM caused by FOXI3 deficiency remains unclear till now. Method In this study, we first constructed a Foxi3 deficiency (Foxi3−/−) mouse model to verify the craniofacial phenotype of Foxi3−/− mice, and then used RNAseq data for gene differential expression analysis to screen candidate pathogenic genes, and conducted gene expression verification analysis using quantitative real‐time PCR. Results By observing the phenotype of Foxi3−/− mice, we found that craniofacial dysmorphism was present. The results of comprehensive bioinformatics analysis suggested that the craniofacial dysmorphism caused by Foxi3 deficiency may be involved in the PI3K‐Akt signaling pathway. Quantitative real‐time PCR results showed that the expression of PI3K‐Akt signaling pathway‐related gene Akt2 was significantly increased in Foxi3−/− mice. Conclusion The craniofacial dysmorphism caused by the deficiency of Foxi3 may be related to the expression of Akt2 and PI3K‐Akt signaling pathway. This study laid a foundation for understanding the function of FOXI3 and the pathogenesis and treatment of related craniofacial dysmorphism caused by FOXI3 dysfunction.

Columnar jointed basalt (CJB) is a kind of jointed rock with a polygonal cylinder mosaic structure that has complex mechanical properties such as discontinuity and heterogeneity. The typical geological structure of the CJB is the intercolumnar joint plane and the implicit joint plane, which obviously affect the mechanical properties of the rock mass. Controlling the unloading relaxation of the CJB is a key problem during the construction of underground engineering. In this paper, in-situ acoustic wave and panoramic borehole camera measurements were carried out in the cavern of the Baihetan project to understand the failure mechanism of the collapse of the CJB. It was quite clear that the evolution of the excavation damage zone (EDZ) of the CJB depends on the time and spatial effects. The closer to the collapse zone, the greater the degree of relaxation failure of the columnar joint rock mass; the further away from the cavern perimeter, the more stable the surrounding rock. The correction between wave velocity and cracks in the rock mass was also discussed. This field test and theoretical analysis can provide a reference for studying the failure mechanism and control measures of CJB in underground caverns under high geostress.

Biological applications of nanomaterials as delivery carriers have been embedded in traditional biomedical research for decades. Despite lagging behind, recent significant breakthroughs in the use of nanocarriers as tools for plant biotechnology have created great interest. In this Perspective, we review the outstanding recent works in nanocarrier-mediated plant transformation and its agricultural applications. We analyze the chemical and physical properties of nanocarriers determining their uptake efficiency and transport throughout the plant body.

Background Socioeconomic development, lifestyle changes and the COVID-19 pandemic all have an impact on people's mental and physical health, which may affect the prevalence of mental disorders. Currently, there is still no sufficient epidemiological information of mental disorders in Xinjiang. Objective To investigate the prevalence and influencing factors of common mental disorders among people aged 15 and above in northern Xinjiang, then compare the data with those of their counterparts in southern Xinjiang, and summarize the overall prevalence of common mental disorders in Xinjiang, providing a scientific basis for the formulation of corresponding mental health plans. Methods From November 2021 to July 2022, a multistage, stratified, random sampling method was used to select 3 853 residents from northern Xinjiang to attend a survey. General Demographic Questionnaire, and self-assessment scales (the 12-Item General Health Questionnaire, Mood Disorder Questionnaire, Symptom Checklist-90, etc.) and other assessment scales (Hamilton Depression Inventory, Bech-Rafaelsen Mania Rating Scale, Brief Psychiatric Rating Scale, etc.) were used as survey instruments. Mental disorders were diagnosed by the ICD-10 classification of mental and behavioral disorders by two psychiatrists with at least five years' working experience, or by a chief or associate chief psychiatrist when there is an inconsistency between the diagnoses made by the two psychiatrists. Results The point prevalence rate and age-adjusted rate of common mental disorders in northern Xinjiang were 9.71% (374/3 853) and 10.07%, respectively. The point prevalence rate and age-adjusted rate of common mental disorders in the whole Xinjiang were 9.69% (750/7 736) and 9.90%, respectively. The point prevalence rates of mood disorders, anxiety disorders, schizophrenia, organic mental disorders, and mental retardation in northern Xinjiang were 4.83% (374/7 736), 3.63% (281/7 736), 0.63% (49/7 736), 0.23% (18/7 736), and 0.36% (28/7 736), respectively. Multivariate Logistic regression analysis for northern Xinjiang showed that: the risk of mood disorders in females was 1.854 times higher than that in males〔95%CI (1.325, 2.593) 〕; The risk of mood disorders increased by 5.210 times in 25-34-year-olds〔95%CI (1.348, 20.143) 〕 and 3.863 times in 35-44-year-olds 〔95%CI (1.030, 14.485) 〕 compared with that in those aged ≥65 years; The risk of mood disorders increased by 0.199 times in those with high school or technical secondary school education〔95%CI (0.078, 0.509) 〕 and 0.147 times in those with two- or three-year college and above education〔95%CI (0.056, 0.388) 〕 compared with that in illiteracies. The risk of anxiety disorder in females was 1.627 times higher than that in males〔95%CI (1.144, 2.315) 〕; The risk of anxiety disorder increased by 0.257 times in 15-24-year-olds〔95%CI (0.091, 0.729) 〕, 0.243 times in 45-54-year-olds〔95%CI (0.101, 0.583) 〕, and 0.210 times in 55-64-year-olds〔95%CI (0.067, 0.661) 〕 compared to that of those aged ≥65 years old. The risk of schizophrenia among people living in villages or towns was 4.762 times higher than that of those living in cities〔95%CI (1.705, 13.300) 〕; The risk of schizophrenia among people with high school or technical secondary school education was 0.079 times higher than that of illiteracies〔95%CI (0.015, 0.405) 〕. Conclusion The prevalence of mood disorders and anxiety disorders is high among all types of mental disorders in Xinjiang. Females, rural people, or low educated people in northern Xinjiang are more prone to various types of mental disorders.

X-ray-based analytics are routinely applied in many fields, including physics, chemistry, materials science, and engineering. The full potential of such techniques in the life sciences and medicine, however, has not yet been fully exploited. We highlight current and upcoming advances in this direction. We describe different X-ray-based methodologies (including those performed at synchrotron light sources and X-ray free-electron lasers) and their potentials for application to investigate the nano-bio interface. The discussion is predominantly guided by asking how such methods could better help to understand and to improve nanoparticle-based drug delivery, though the concepts also apply to nano-bio interactions in general. We discuss current limitations and how they might be overcome, particularly for future use in vivo.