Highlights
Recent advances in bacterial theranostics using antimicrobial photo/sonodynamic therapy (aPDT/SDT) are summarized in this review.
The inherent optical characteristics of ...photo/sonosensitizers facilely enable imaging diagnosis of bacterial infections.
Reactive oxygen species as the killing effector of aPDT/SDT cause broad-spectrum damage for sterilization with no concern about antibiotic resistance.
Rapid evolution and propagation of multidrug resistance among bacterial pathogens are outpacing the development of new antibiotics, but antimicrobial photodynamic therapy (aPDT) provides an excellent alternative. This treatment depends on the interaction between light and photoactivated sensitizer to generate reactive oxygen species (ROS), which are highly cytotoxic to induce apoptosis in virtually all microorganisms without resistance concern. When replacing light with low-frequency ultrasonic wave to activate sensitizer, a novel ultrasound-driven treatment emerges as antimicrobial sonodynamic therapy (aSDT). Recent advances in aPDT and aSDT reveal golden opportunities for the management of multidrug resistant bacterial infections, especially in the theranostic application where imaging diagnosis can be accomplished facilely with the inherent optical characteristics of sensitizers, and the generated ROS by aPDT/SDT cause broad-spectrum oxidative damage for sterilization. In this review, we systemically outline the mechanisms, targets, and current progress of aPDT/SDT for bacterial theranostic application. Furthermore, potential limitations and future perspectives are also highlighted.
Previous studies based on voxel-based morphometry (VBM) had revealed brain gray matter (GM) changes in chronic smokers relative to nonsmokers. However, not all studies reported entirely consistent ...findings, or even opposite. The aim of this study was to conduct a quantitative meta-analysis of VBM studies of chronic smokers.
A systematic database search was conducted in PubMed and Web of Knowledge from January 1, 2000 to January 31, 2020 to identify eligible VBM studies. Meta-analysis was performed with the Seed-based d Mapping software package to compare alternations between chronic cigarette smokers and nonsmokers. In addition, meta-regression analysis were performed to examine the influences of cigarette per day, smoking history and FTND.
A total of 17 VBM studies including 905 smokers and 1344 nonsmokers met the inclusion criteria. The results of this meta-analysis showed that the chronic smokers showed a robust GM volume decrease in bilateral prefrontal cortex and left insular and a GM increase in the right lingual cortex and left occipital cortex. Moreover, meta-regression analysis showed that cigarette per day, smoking history and FTND were partly associated with GM changes in chronic smokers.
This meta-analysis indicated that chronic cigarette smokers had significant and robust brain GM alternations compared with nonsmokers. Longitudinal studies should be performed in the future to explore whether these brain regions could be used as potential therapeutic neuro-target for nicotine dependence.
Extraskeletal mesenchymal chondrosarcoma (ESMC) originate from the nasal cavity have rarely been reported, especially its imaging features, which makes the preoperative diagnosis difficult. Here, we ...report the clinical, computed tomography, and magnetic resonance imaging features of a 60-year-old female patient with pathologically confirmed ESMC in the nasal cavity to help provide more reference for diagnosis before operation. Extraskeletal mesenchymal chondrosarcoma in the nasal cavity demonstrates typical imaging features, such as mesh-like enhancement, calcification, hemorrhage, necrosis, cystic degeneration, and so on.
The epithelial-to-mesenchymal transition (EMT) is a vital control point in metastatic breast cancer (MBC). TWIST1, SNAIL1, SLUG, and ZEB1, as key EMT-inducing transcription factors (EMT-TFs), are ...involved in MBC through different signaling cascades. This updated meta-analysis was conducted to assess the correlation between the expression of EMT-TFs and prognostic value in MBC patients. A total of 3,218 MBC patients from fourteen eligible studies were evaluated. The pooled hazard ratios (HR) for EMT-TFs suggested that high EMT-TF expression was significantly associated with poor prognosis in MBC patients (HRs = 1.72; 95% confidence intervals (CIs) = 1.53-1.93; P = 0.001). In addition, the overexpression of SLUG was the most impactful on the risk of MBC compared with TWIST1 and SNAIL1, which sponsored fixed models. Strikingly, the increased risk of MBC was less associated with ZEB1 expression. However, the EMT-TF expression levels significantly increased the risk of MBC in the Asian population (HR = 2.11, 95% CI = 1.70-2.62) without any publication bias (t = 1.70, P = 0.11). These findings suggest that the overexpression of potentially TWIST1, SNAIL1 and especially SLUG play a key role in the aggregation of MBC treatment as well as in the improvement of follow-up plans in Asian MBC patients.
Patients with major depressive disorder (MDD) exhibit concurrent deficits in both sensory and higher-order cognitive processing. Connectome studies have suggested a principal primary-to-transmodal ...gradient in functional brain networks, supporting the spectrum from sensation to cognition. However, whether this gradient structure is disrupted in patients with MDD and how this disruption associates with gene expression profiles and treatment outcome remain unknown. Using a large cohort of resting-state fMRI data from 2227 participants (1148 MDD patients and 1079 healthy controls) recruited at nine sites, we investigated MDD-related alterations in the principal connectome gradient. We further used Neurosynth, postmortem gene expression, and an 8-week antidepressant treatment (20 MDD patients) data to assess the meta-analytic cognitive functions, transcriptional profiles, and treatment outcomes related to MDD gradient alterations, respectively. Relative to the controls, MDD patients exhibited global topographic alterations in the principal primary-to-transmodal gradient, including reduced explanation ratio, gradient range, and gradient variation (Cohen's d = 0.16-0.21), and focal alterations mainly in the primary and transmodal systems (d = 0.18-0.25). These gradient alterations were significantly correlated with meta-analytic terms involving sensory processing and higher-order cognition. The transcriptional profiles explained 53.9% variance of the altered gradient pattern, with the most correlated genes enriched in transsynaptic signaling and calcium ion binding. The baseline gradient maps of patients significantly predicted symptomatic improvement after treatment. These results highlight the connectome gradient dysfunction in MDD and its linkage with gene expression profiles and clinical management, providing insight into the neurobiological underpinnings and potential biomarkers for treatment evaluation in this disorder.
To quantitatively compare the potential of various diffusion parameters obtained from monoexponential, biexponential, and stretched exponential diffusion-weighted imaging models and diffusion ...kurtosis imaging in the grading of gliomas.
This study was approved by the local ethics committee, and written informed consent was obtained from all subjects. Both diffusion-weighted imaging and diffusion kurtosis imaging were performed in 69 patients with pathologically proven gliomas by using a 3-T magnetic resonance (MR) imaging unit. An isotropic apparent diffusion coefficient (ADC), true ADC, pseudo-ADC, and perfusion fraction were calculated from diffusion-weighted images by using a biexponential model. A water molecular diffusion heterogeneity index and distributed diffusion coefficient were calculated from diffusion-weighted images by using a stretched exponential model. Mean diffusivity, fractional anisotropy, and mean kurtosis were calculated from diffusion kurtosis images. All values were compared between high-grade and low-grade gliomas by using a Mann-Whitney U test. Receiver operating characteristic and Spearman rank correlation analysis were used for statistical evaluations.
ADC, true ADC, perfusion fraction, water molecular diffusion heterogeneity index, distributed diffusion coefficient, and mean diffusivity values were significantly lower in high-grade gliomas than in low-grade gliomas (U = 109, 56, 129, 6, 206, and 229, respectively; P < .05). Pseudo-ADC and mean kurtosis values were significantly higher in high-grade gliomas than in low-grade gliomas (U = 98 and 8, respectively; P < .05). Both water molecular diffusion heterogeneity index (area under the receiver operating characteristic curve AUC = 0.993) and mean kurtosis (AUC = 0.991) had significantly greater AUC values than ADC (AUC = 0.866), mean diffusivity (AUC = 0.722), and fractional anisotropy (AUC = 0.500) in the differentiation of low-grade and high-grade gliomas (P < .05).
Water molecular diffusion heterogeneity index and mean kurtosis values may provide additional information and improve the grading of gliomas compared with conventional diffusion parameters.
Abstract
The Yi is one of fifty-six ethnic populations and one of the most ancient ethnic groups in China. The Liangshan Yi Autonomous Prefecture (LYAP) in Sichuan Province has the single largest Yi ...community in China. To establish a Yi population database in the LYAP of Sichuan in China, a Goldeneye™ DNA Identification System 20A Kit with 19 autosomal STRs (short tandem repeats) was used. As a result, the total discrimination power (TDP) and the cumulative probability of exclusion (CPE) for these STRs in 1016 unrelated individuals were 0.999999999999999999999897 and 0.9999999597, respectively. Totals of 273 alleles for 19 STRs and 8–22 alleles for each locus were found. The allelic frequencies ranged from 0.0005 to 0.5084. The forensic parameter averages of these STRs were as follows: observed heterozygosity (H
obs
) of 78.44%, expected heterozygosity (H
exp
) of 79.89%, discrimination power (DP) of 92.66%, and probability of exclusion (PE) of 57.68%. Penta E presented the highest levels of H
obs
and DP, whereas TPOX showed the lowest H
obs
and DP values. Nei’s standard genetic distance matrix among 31 populations found that the nearest genetic distance to the Yi population was the Sichuan Han (0.0056). Altogether, we first reported the forensic parameters and allele frequencies of 19 autosomal STRs of the Yi group in Liangshan. These 19 STR makers could provide highly informative polymorphisms for individual identification, paternity testing and genetic population analyses.
MicroRNA-34a (miR-34a), a tumor suppressor, has been reported to be dysregulated in various human cancers. MiR-34a is involves in certain epithelial-mesenchymal transition (EMT)-associated signal ...pathways to repress tumorigenesis, cancer progression, and metastasis. Due to the particularity of miR-34 family in tumor-associated EMT, the significance of miR-34a is being increasingly recognized. Competing endogenous RNA (ceRNA) is a novel concept involving mRNA, circular RNA, pseudogene transcript, and long noncoding RNA regulating each other's expressions using microRNA response elements to compete for the binding of microRNAs. Studies showed that miR-34a is efficient for cancer therapy. Here, we provide an overview of the function of miR-34a in tumor-associated EMT. ceRNA hypothesis plays an important role in miR-34a regulation in EMT, cancer progression, and metastasis. Its potential roles and challenges as a microRNA therapeutic candidate are discussed. As the negative effect on cancer progression, miR-34a should play crucial roles in clinical diagnosis and cancer therapy.
Reliable mapping of system-level individual differences is a critical first step toward precision medicine for complex disorders such as schizophrenia. Disrupted structural covariance indicates a ...system-level brain maturational disruption in schizophrenia. However, most studies examine structural covariance at the group level. This prevents subject-level inferences. Here, we introduce a Network Template Perturbation approach to construct individual differential structural covariance network (IDSCN) using regional gray-matter volume. IDSCN quantifies how structural covariance between two nodes in a patient deviates from the normative covariance in healthy subjects. We analyzed T1 images from 1287 subjects, including 107 first-episode (drug-naive) patients and 71 controls in the discovery datasets and established robustness in 213 first-episode (drug-naive), 294 chronic, 99 clinical high-risk patients, and 494 controls from the replication datasets. Patients with schizophrenia were highly variable in their altered structural covariance edges; the number of altered edges was related to severity of hallucinations. Despite this variability, a subset of covariance edges, including the left hippocampus-bilateral putamen/globus pallidus edges, clustered patients into two distinct subgroups with opposing changes in covariance compared to controls, and significant differences in their anxiety and depression scores. These subgroup differences were stable across all seven datasets with meaningful genetic associations and functional annotation for the affected edges. We conclude that the underlying physiology of affective symptoms in schizophrenia involves the hippocampus and putamen/pallidum, predates disease onset, and is sufficiently consistent to resolve morphological heterogeneity throughout the illness course. The two schizophrenia subgroups identified thus have implications for the nosology and clinical treatment.
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