Bionic nanotheranostic for multimodal imaging-guided NIR-II-photothermal cancer therapy.

In photothermal therapy (PTT), the photothermal conversion of the second near-infrared (NIR-II) window allows deeper penetration and higher laser irradiance and is considered a promising therapeutic strategy for deep tissues. Since cancer remains a leading cause of deaths worldwide, despite the numerous treatment options, we aimed to develop an improved bionic nanotheranostic for combined imaging and photothermal cancer therapy. We combined a gold nanobipyramid (Au NBP) as a photothermal agent and MnO2 as a magnetic resonance enhancer to produce core/shell structures (Au@MnO2; AM) and modified their surfaces with homologous cancer cell plasma membranes (PM) to enable tumour targeting. The performance of the resulting Au@MnO2@PM (AMP) nanotheranostic was evaluated in vitro and in vivo. AMP exhibits photothermal properties under NIR-II laser irradiation and has multimodal in vitro imaging functions. AMP enables the computed tomography (CT), photothermal imaging (PTI), and magnetic resonance imaging (MRI) of tumours. In particular, AMP exhibited a remarkable PTT effect on cancer cells in vitro and inhibited tumour cell growth under 1064 nm laser irradiation in vivo, with no significant systemic toxicity. This study achieved tumour therapy guided by multimodal imaging, thereby demonstrating a novel strategy for the use of bionic gold nanoparticles for tumour PTT under NIR-II laser irradiation.

White matter microstructural alterations in patients with anti-N-methyl-D-aspartate receptor encephalitis: A tract-based spatial statistics study.

BACKGROUND: Cognitive impairment is common in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis; however, neural mechanisms underlying this impairment remain unclear. Diffusion tensor imaging (DTI) is a potential method for studying the condition of white matter fibers in patients with anti-NMDAR encephalitis, allowing for an analysis of the neuroimaging mechanisms of cognitive impairment in conjunction with cognitive scales. This study aimed to explore white matter microstructural alterations and their correlation with cognitive function in patients with anti-NMDAR encephalitis. METHODS: DTI data were collected from 22 patients with anti-NMDAR encephalitis (aged 29.00(19.75, 39.50) years; 12 males, 10 females) and 20 healthy controls (HCs) (aged 24.50(21.25, 32.00); 12 males, 8 females) matched for age, sex, and educational level. Changes in the white matter microstructure were analyzed using tract-based spatial statistics. Pearson correlation analysis was used to explore the correlation between white matter integrity and neuropsychological scores. RESULTS: Compared with HCs, patients with anti-NMDAR encephalitis showed decreased fractional anisotropy and increased mean diffusivity values in extensive white matter regions, which were associated with disease severity, memory, and executive and visuospatial functions. CONCLUSION: Widespread impairment of the structural integrity of the white matter in the brain is significantly associated with cognitive dysfunction in patients with anti-NMDAR encephalitis, providing neuroimaging evidence for studying the underlying mechanisms.

Functional connectivity changes of the hippocampal subregions in anti-N-methyl-D-aspartate receptor encephalitis.

The hippocampus plays an important role in the pathophysiological mechanism of Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Nevertheless, the connection between the resting-state activity of the hippocampal subregions and neuropsychiatric disorders in patients remains unclear. This study aimed to explore the changes in functional connectivity (FC) in the hippocampal subregions of patients with anti-NMDAR encephalitis and its association with clinical symptoms and cognitive performance. Twenty-three patients with anti-NMDAR encephalitis and 23 healthy controls (HC) were recruited. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans and completed clinical cognitive scales. Based on the Brainnetome Atlas, the rostral (anterior) and caudal (posterior) hippocampi of both the left and right hemispheres were selected as regions of interest (ROIs) for FC analysis. First, a one-sample t-test was used to observe the whole-brain connectivity distribution of hippocampal subregions within the patient and HC groups at a threshold of p < 0.05. The two-sample t-test was used to compare the differences in hippocampal ROIs connectivity between groups, followed by a partial correlation analysis between the FC values of brain regions with statistical differences and clinical variables. This study observed that the distribution of whole-brain functional connectivity in the rostral and caudal hippocampi aligned with the connectivity differences between the anterior and posterior hippocampi. Compared to the HC group, the patients showed significantly decreased FC between the bilateral rostral hippocampus and the left inferior orbitofrontal gyrus and between the right rostral hippocampus and the right cerebellum. However, a significant increase in FC was observed between the right rostral hippocampus and left superior temporal gyrus, the left caudal hippocampus and right superior frontal gyrus, and the right caudal hippocampus and left gyrus rectus. Partial correlation analysis showed that FC between the left inferior orbitofrontal gyrus and the right rostral hippocampus was significantly negatively correlated with the California Verbal Learning Test (CVLT) and Brief Visuospatial Memory Test (BVMT) scores. The FC between the right rostral hippocampus and the left superior temporal gyrus was negatively correlated with BVMT scores. FC abnormalities in the hippocampal subregions of patients with anti-NMDAR encephalitis were associated with cognitive impairment, emotional changes, and seizures. These results may help explain the pathophysiological mechanisms and clinical manifestations of anti-NMDAR encephalitis and NMDAR dysfunction-related diseases such as schizophrenia.

Communication Matters: The Role of Patient-Centered Communication in Improving Old Adults' Health Competence and Health Outcomes.

Research has demonstrated links between patient-centered communication (PCC) and patients' health outcomes. However, little is known about the underlying processes that may mediate the relationship. This study is one of the first to examine the influence of PCC on older adults' health outcomes, as well as the mediation role of health competence, from a longitudinal perspective. With a general basis of Street et al.'s pathway model, we proposed and tested mediation pathways linking patient-centered communication to the older population's general and mental health, mediated by health competence. Data from 2011, 2017 and 2020 iterations of the Health Information National Trends Survey (HINTS) were used for this study. This study focused on older adults aged 60 and above. Results indicated that after controlling participants' age, gender, education, income and race, PCC is related to the older people's health outcomes either directly or indirectly, irrespective of time series. Specifically, health competence was found to significantly mediate the associations between PCC and the older adults' general health or mental health over the three iterations. Noteworthily, findings from this study also revealed that different dimensions of PCC might exert different influences on older patients' health competence and health outcomes.

Sex-specific grey matter abnormalities in individuals with chronic insomnia.

Previous studies have reported sex differences in altered brain function in patients with chronic insomnia (CI). However, sex-related alterations in brain morphology have rarely been investigated. This study aimed to investigate sex-specific grey matter (GM) alterations in patients with CI and to examine the relationship between GM alterations and neuropsychological assessments. Ninety-three (65 females and 28 males) patients and 78 healthy (50 females and 28 males) controls were recruited. Structural magnetic resonance imaging data were analysed using voxel-based morphometry to test for interactions between sex and diagnosis. Spearman's correlation was used to assess the associations among structure, disease duration, and sleep-, mood-, and cognition-related assessments. Males with CI showed reduced GM volume in the left inferior parietal lobe, left middle cingulate cortex, and right supramarginal gyrus. Females with CI showed increased GM volume in the right Rolandic operculum. Moreover, mood-related assessments were negatively correlated with GM volumes in the right supramarginal gyrus and left inferior parietal lobe in the male patients, and cognitive-related assessments were positively correlated with GM volumes in the Rolandic operculum in the female patients. Our findings indicate sex-specific alterations in brain morphology in CI, thereby broadening our understanding of sex differences in CI and potentially providing complementary evidence for the development of more effective therapies and individual treatments.

Enhanced functional connectome of cerebellum in chronic insomnia patients.

BACKGROUND: Functional abnormalities of the cerebellum have been found to be closely associated with chronic insomnia (CI). However, whether there are abnormalities in the topology of the functional connectome of the cerebellum in these patients is still unknown. This study aimed to investigate topological abnormalities of the cerebellar functional connectome in individuals with CI. MATERIALS AND METHODS: We used resting-state functional magnetic resonance imaging (rs-fMRI) and graph-theoretic analysis to construct a functional connectivity matrix and extract topological property features of the cerebellar functional connectome in patients with CI. We examined global and nodal topological property changes in the cerebellar functional connectome in 102 patients with CI (CI group) and 101 healthy participants without insomnia symptoms (HC group) to determine the differences between groups. Correlations between the topological properties of the cerebellar functional connectome and clinical assessments were calculated to confirm the differences between groups. RESULTS: The cerebellar functional connectome of both CI and HC patients exhibited small-world properties. The CI group showed higher standardized clustering coefficients at the global properties and higher betweenness centrality in the cerebellar Crus II vermis region at the nodal properties compared with participants in the HC group. However, the topological properties of cerebellar functional connectome abnormalities in the CI group were not significantly different from those in clinical assessments. CONCLUSION: Our findings suggest that the abnormal global and nodal topological properties of the cerebellar functional connectome are associated with CI and could serve as an important biomarker for CI.

Aberrant brain entropy in posttraumatic stress disorder comorbid with major depressive disorder during the coronavirus disease 2019 pandemic.

Aim: Previously, neuroimaging studies on comorbid Posttraumatic-Major depression disorder (PTSD-MDD) comorbidity found abnormalities in multiple brain regions among patients. Recent neuroimaging studies have revealed dynamic nature on human brain activity during resting state, and entropy as an indicator of dynamic regularity may provide a new perspective for studying abnormalities of brain function among PTSD-MDD patients. During the COVID-19 pandemic, there has been a significant increase in the number of patients with PTSD-MDD. We have decided to conduct research on resting-state brain functional activity of patients who developed PTSD-MDD during this period using entropy. Methods: Thirty three patients with PTSD-MDD and 36 matched TCs were recruited. PTSD and depression symptoms were assessed using multiple clinical scales. All subjects underwent functional magnetic resonance imaging (fMRI) scans. And the brain entropy (BEN) maps were calculated using the BEN mapping toolbox. A two-sample t-test was used to compare the differences in the brain entropy between the PTSD-MDD comorbidity group and TC group. Furthermore, correlation analysis was conducted between the BEN changes in patients with PTSD-MDD and clinical scales. Results: Compared to the TCs, PTSD-MDD patients had a reduced BEN in the right middle frontal orbital gyrus (R_MFOG), left putamen, and right inferior frontal gyrus, opercular part (R_IFOG). Furthermore, a higher BEN in the R_MFOG was related to higher CAPS and HAMD-24 scores in the patients with PTSD-MDD. Conclusion: The results showed that the R_MFOG is a potential marker for showing the symptom severity of PTSD-MDD comorbidity. Consequently, PTSD-MDD may have reduced BEN in frontal and basal ganglia regions which are related to emotional dysregulation and cognitive deficits.

Predicting insomnia severity using structure-function coupling in female chronic insomnia patients.

Functional connectivity between brain regions is constrained by the underlying structural pathways. However, how this structure-function coupling is disrupted in female patients with insomnia disorder is unclear. This study examines if the whole-brain pattern of structure-function coupling could be used to predict unseen female patients' insomnia severity index. Resting-state functional MRI and diffusion-weighted imaging were performed in 82 female participants with chronic insomnia. Structure-function coupling was computed using the Spearman rank correlations between structural and functional connectivity profiles. Using relevance vector regression approach and 10-fold cross-validation, we predicted the individuals' insomnia severity index using the pattern of whole-brain structure-function coupling. Finally, we extracted the contribution of each regional coupling to the prediction model. The pattern of structure-function coupling could be used to significantly predict unseen individuals' insomnia severity index scores (r = 0.29, permutation P < 0.001; mean absolute error (MAE) = 4.59, permutation P < 0.001). Moreover, the brain regions with high functional hierarchy, including regions in the default mode network, mainly displayed negative contribution weights, while the regions with lower functional hierarchy, including occipital regions and the precentral gyrus, mainly displayed positive contribution weights. This is the first study to demonstrate an association between structure-function coupling and the insomnia severity index in females with insomnia disorder. Importantly, our data suggest that insomnia severity is associated with a reduction in structure-function coupling in higher-order brain regions and an increase in structure-function coupling in lower-order brain regions.

Diagnostic identification of chronic insomnia using ALFF and FC features of resting-state functional MRI and logistic regression approach.

This study investigated whether the amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) features could be used as potentially neurological markers to identify chronic insomnia (CI) using resting-state functional MRI and machine learning method logistic regression (LR). This study included 49 CI patients and 47 healthy controls (HC). Voxel-wise features, including the amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC), were extracted from resting-state functional magnetic resonance brain images. Then, we divided the data into two independent cohorts for training (44 CI patients and 42 HC patients), and independent validation (5 CI patients and 5 HC patients) by using logistic regression. The model was evaluated using 20 rounds of fivefold cross­validation for training. In particular, a two-sample t-test (GRF corrected, p-voxel < 0.001, p-cluster < 0.05) was used for feature selection during the model training. Finally, single­shot testing of the final model was performed on the independent validation cohort. A correlation analysis (Bonferroni correction, p < 0.05/4) was also conducted to determine whether the features contributing to the prediction were correlated with clinical characteristics, including the Insomnia Severity Index (ISI), Pittsburgh sleep quality index (PSQI), self-rating anxiety scale (SAS), and self-rating depression scale (SDS). Results showed that resting-state features had a discrimination accuracy of 86.40%, with a sensitivity of 93.00% and specificity of 79.80%. The area under the curve (AUC) was 0.89 (all [Formula: see text]< 0.001). The ALFF and FC features showed significant differences between the CI patients and HC. The regions contributing to the prediction mainly included the anterior cingulate, prefrontal cortex, orbital part of the frontal lobe, angular gyrus, cingulate gyrus, praecuneus, parietal lobe, temporal gyrus, superior temporal gyrus, and middle temporal gyrus. Furthermore, some specific functional connectivity among related regions was positively correlated with the ISI, and also negatively related to the SDS in correlation analysis. Our current study suggested that ALFF and FC in the regions contributing to diagnostic identification might serve as potential neuromarkers for CI.

Enhanced intrathalamic morphological connectivity in patients with chronic insomnia.

This study aimed to systematically investigate abnormal morphological connectivity in subregions of the thalamus and examine the clinical relevance of this connectivity in patients with chronic insomnia. One hundred and two patients with chronic insomnia (aged 45.50 [34.75 ~ 58.00] years; 24 men, 78 women) and one hundred and one healthy controls (aged 45.00 [34.00 ~ 55.00] years; 32 men, 69 women) were recruited. Intrathalamic and thalamocortical morphological connectivity in the thalamic subregions defined in the Human Brainnetome Atlas were computed and compared between the two groups. Spearman's correlation was used to estimate the association between thalamic morphological connectivity alterations and clinical variables. Compared with the control group, the insomnia group exhibited higher intrathalamic mean morphological connectivity than the control group, though no alterations in thalamocortical morphological connectivity were observed. However, no correlation was found between altered intrathalamic morphological connectivity and behavioral scales. In addition, alterations in morphological connectivity among thalamic subregions were found mainly in the left medial premotor thalamus, left medial prefrontal thalamus, and left sensory thalamus; however, these results were no longer significant after correction. Our findings suggest increased intrathalamic morphological connectivity in patients with chronic insomnia, thus enriching the understanding of morphological connectivity at the individual level and providing new perspectives for clinical interventions and diagnostic imaging.

Functional Connectivity Disturbances of the Locus Coeruleus in Chronic Insomnia Disorder.

Introduction: In recent years, people have gained a profound understanding of chronic insomnia disorder (CID), but the pathophysiological mechanism of CID is still unclear. There is some evidence that the locus coeruleus (LC) is involved in the regulation of wakefulness in CID, but there have been few studies using brain functional imaging. The purpose of this study was to evaluate the resting-state functional connectivity (FC) between the LC and other brain voxels in CID and whether these abnormal FC are involved in the regulation of wakefulness. Methods: A total of 49 patients with chronic insomnia disorder and 47 healthy controls (HC) matched for gender, age, and education were examined with rs-fMRI in this study. The LC was selected as the region of interest, and then seed-based analysis was conducted on the LC and other voxels to obtain the brain regions with abnormal FC. The correlation between the FC value of the abnormal connection area and the clinical scale score was analyzed. Results: Compared with the HC, the FC between the LC and right precuneus, right posterior cingulate cortex, left middle temporal gyrus, left calcarine, and right superior orbitofrontal cortex was significantly enhanced (p < 0.05, FDR correction), and the functional connectivity signal value between the locus coeruleus and left middle temporal gyrus was positively correlated with the Self-Rating Depression Scale (p = 0.021). Conclusion: The abnormal FC between the LC and multiple brain regions may contribute to a better understanding of the neurobiological mechanism of CID.

Differentiation of Thyroid Nodules (C-TIRADS 4) by Combining Contrast-Enhanced Ultrasound Diagnosis Model With Chinese Thyroid Imaging Reporting and Data System.

Objectives: To establish a contrast-enhanced ultrasound (CEUS) diagnostic schedule by CEUS analysis of thyroid nodules of C-TIRADS 4. To establish a CEUS-TIRADS diagnostic model to differentiate thyroid nodules (C-TIRADS 4) by combining CEUS with Chinese thyroid imaging reporting and data system (C-TIRADS). Methods: A total of 228 thyroid nodules (C-TIRADS 4) were estimated by CEUS. The arrival time, enhancement degree, enhancement homogeneity, enhancement pattern, enhancement ring, and wash-out time were analyzed in CEUS for all of the nodules. Multivariate factors logistic analysis was performed and a CEUS diagnostic schedule was established. If the nodule had a regular hyper-enhancement ring or got a score of less than 2 in CEUS analysis, CEUS-TIRADS subtracted 1 category. If the nodule got a score of 2 in the CEUS schedule, the CEUS-TIRADS category remained the same as before. If the nodule got a score of more than 2 in the CEUS schedule, CEUS-TIRADS added 1 category. When it reflected an absent enhancement in CEUS, the nodule was judged as CEUS-TIRADS 3. All of the C-TIRADS 4 nodules were re-graded by CEUS-TIRADS. We then compare the diagnosis performance of C-TIRADS, CEUS, and CEUS-TIRADS by sensitivity, specificity, and accuracy. Results: Among the 228 C-TIRADS 4 nodules, 69 were determined as C-TIRADS 4a, 114 were C-TIRADS 4b, and 45 were C-TIRADS 4c. The sensitivity, specificity, and accuracy of C-TIRADS were 93.1%, 55.3%, and 74.6% respectively. The area under the curve was 0.753. Later arrival time, hypo-enhancement, heterogeneous enhancement, centripetal enhancement, and rapid washout were risk factors of malignancy in multivariate analysis. The sensitivity, specificity, and accuracy of CEUS were 78.7%, 87.5%, and 83.3% respectively. The area under the curve was 0.803. By CEUS-TIRADS diagnostic model combining CEUS with C-TIRADS, a total of 127 cases were determined as malignancy (111 were malignant and 16 were benign) and 101 were diagnosed as benign ones (5 were malignant and 96 were benign). The sensitivity, specificity, and accuracy of CEUS-TIRADS were 95.7%, 85.7%, and 92.1% respectively. The area under the curve was 0.916. The diagnostic performance of CEUS-TIRADS was significantly better than CEUS and C-TIRADS. The difference was statistically significant (P<0.05). Conclusions: The diagnostic schedule of CEUS could get better diagnostic performance than US in the differentiation of thyroid nodules. The CEUS-TIRADS combining CEUS analysis with C-TIRADS could make up for the deficient sensibility of C-TIRADS, showing a better diagnostic performance than US and CEUS.

Abnormal Degree Centrality in Children with Low-Function Autism Spectrum Disorders: A Sleeping-State Functional Magnetic Resonance Imaging Study.

Purpose: This study used the graph-theory approach, degree centrality (DC) to analyze whole-brain functional networks at the voxel level in children with ASD, and investigated whether DC changes were correlated with any clinical variables in ASD children. Methods: The current study included 86 children with ASD and 54 matched healthy subjects Aged 2-5.5 years. Next, chloral hydrate induced sleeping-state functional magnetic resonance imaging (ss-fMRI) datasets were acquired from these ASD and healthy subjects. For a given voxel, the DC was calculated by calculating the number of functional connections with significantly positive correlations at the individual level. Group differences were tested using two-sample t-tests (p < 0.01, AlphaSim corrected). Finally, relationships between abnormal DCs and clinical variables were investigated via Pearson's correlation analysis. Results: Children with ASD exhibited low DC values in the right middle frontal gyrus (MFG) (p < 0.01, AlphaSim corrected). Furthermore, significantly negative correlations were established between the decreased average DC values within the right MFG in ASD children and the total ABC scores, as well as with two ABC subscales measuring highly relevant impairments in ASD (ie, stereotypes and object-use behaviors and difficulties in language). Conclusion: Taken together, the results of our ss-fMRI study suggest that abnormal DC may represent an important contribution to elucidation of the neuropathophysiological mechanisms of preschoolers with ASD.

Reduced left lateralized functional connectivity of the thalamic subregions between short-term and chronic insomnia disorder.

The purpose of the study was to systematically investigate the structural and functional abnormalities in the subregions of the thalamus and to examine their clinical relevance in patients with short-term and chronic insomnia disorder (ID). Thirty-four patients with short-term ID, 41 patients with chronic ID, and 46 healthy controls (HCs) were recruited. Grey matter volume and seed-based resting-state functional connectivity (RSFC) were compared for each thalamic subregion (bilateral cTtha, lPFtha, mPFtha, mPMtha, Otha, Pptha, rTtha, and Stha) between the three groups. Spearman's correlation was used to estimate the associations between thalamic alterations and clinical variables. Compared with the HCs and chronic ID group, the short-term ID group exhibited lower RSFC of the left cTtha, lPFtha, Otha and Pptha with the bilateral caudate. In addition, the short-term ID group exhibited lower RSFC between the left mPFtha and left caudate in comparison with the other two groups. Convergent RSFC alterations were found in the left cTtha and Otha with the right parahippocampal gyrus in both ID groups. Moreover, a positive correlation was found for the left Otha-caudate RSFC with the Epworth sleepiness scale scores (r = 0.340, P = 0.040). Our findings suggest shared and unique RSFC alterations of certain thalamic subregions with paralimbic regions between short-term and chronic ID. These findings have implications for understanding common and specific pathophysiology of different types of ID.

Rational design of non-toxic GOx-based biocatalytic nanoreactor for multimodal synergistic therapy and tumor metastasis suppression.

Rationale: Glucose oxidase (GOx)-based biocatalytic nanoreactors can cut off the energy supply of tumors for starvation therapy and deoxygenation-activated chemotherapy. However, these nanoreactors, including mesoporous silica, calcium phosphate, metal-organic framework, or polymer nanocarriers, cannot completely block the reaction of GOx with glucose in the blood, inducing systemic toxicity from hydrogen peroxide (H2O2) and anoxia. The low enzyme loading capacity can reduce systemic toxicity but limits its therapeutic effect. Here, we describe a real 'ON/OFF' intelligent nanoreactor with a core-shell structure (GOx + tirazapamine (TPZ))/ZIF-8@ZIF-8 modified with the red cell membrane (GTZ@Z-RBM) for cargo delivery. Methods: GTZ@Z-RBM nanoparticles (NPs) were prepared by the co-precipitation and epitaxial growth process under mild conditions. The core-shell structure loaded with GOx and TPZ was characterized for hydrate particle size and surface charge. The GTZ@Z-RBM NPs morphology, drug, and GOx loading/releasing abilities, system toxicity, multimodal synergistic therapy, and tumor metastasis suppression were investigated. The in vitro and in vivo outcomes of GTZ@Z-RBM NPs were assessed in 4T1 breast cancer cells. Results: GTZ@Z-RBM NPs could spatially isolate the enzyme from glucose in a physiological environment, reducing systemic toxicity. The fabricated nanoreactor with high enzyme loading capacity and good biocompatibility could deliver GOx and TPZ to the tumors, thereby exhausting glucose, generating H2O2, and aggravating hypoxic microenvironment for starvation therapy, DNA damage, and deoxygenation-activated chemotherapy. Significantly, the synergistic therapy effectively suppressed the breast cancer metastasis in mice and prolonged life without systemic toxicity. The in vitro and in vivo results provided evidence that our biomimetic nanoreactor had a powerful synergistic cascade effect in treating breast cancer. Conclusion: GTZ@Z-RBM NPs can be used as an 'ON/OFF' intelligent nanoreactor to deliver GOx and TPZ for multimodal synergistic therapy and tumor metastasis suppression.

Image-guided selection of Gd@C-dots as sensitizers to improve radiotherapy of non-small cell lung cancer.

BACKGROUND: Recently, gadolinium-intercalated carbon dots (Gd@C-dots) have demonstrated potential advantages over traditional high-Z nanoparticles (HZNPs) as radiosensitizers due to their high stability, minimal metal leakage, and remarkable efficacy. RESULTS: In this work, two Gd@C-dots formulations were fabricated which bore carboxylic acid (CA-Gd@C-dots) or amino group (pPD-Gd@C-dots), respectively, on the carbon shell. While it is critical to develop innovative nanomateirals for cancer therapy, determining their tumor accumulation and retention is equally important. Therefore, in vivo positron emission tomography (PET) was performed, which found that 64Cu-labeled pPD-Gd@C-dots demonstrated significantly improved tumor retention (up to 48 h post injection) compared with CA-Gd@C-dots. Indeed, cell uptake of 64Cu-pPD-Gd@C-dots reached close to 60% of total dose compared with ~ 5% of 64Cu-CA-Gd@C-dots. pPD-Gd@C-dots was therefore further evaluated as a new radiosensitizer for non-small cell lung cancer treatment. While single dose radiation plus intratumorally injected pPD-Gd@C-dots did lead to improved tumor suppression, the inhibition effect was further improved with two doses of radiation. The persistent retention of pPD-Gd@C-dots in tumor region eliminates the need of reinjecting radiosensitizer for the second radiation. CONCLUSIONS: PET offers a simple and straightforward way to study nanoparticle retention in vivo, and the selected pPD-Gd@C-dots hold great potential as an effective radiosensitizer.

Diagnostic classification of coronavirus disease 2019 (COVID-19) and other pneumonias using radiomics features in CT chest images.

We propose a classification method using the radiomics features of CT chest images to identify patients with coronavirus disease 2019 (COVID-19) and other pneumonias. The chest CT images of two groups of participants (90 COVID-19 patients who were confirmed as positive by nucleic acid test of RT-PCR and 90 other pneumonias patients) were collected, and the two groups of data were manually drawn to outline the region of interest (ROI) of pneumonias. The radiomics method was used to extract textural features and histogram features of the ROI and obtain a radiomics features vector from each sample. Then, we divided the data into two independent radiomic cohorts for training (70 COVID-19 patients and 70 other pneumonias patients), and validation (20 COVID-19 patients and 20 other pneumonias patients) by using support vector machine (SVM). This model used 20 rounds of tenfold cross-validation for training. Finally, single-shot testing of the final model was performed on the independent validation cohort. In the COVID-19 patients, correlation analysis (multiple comparison correction-Bonferroni correction, P < 0.05/7) was also conducted to determine whether the textural and histogram features were correlated with the laboratory test index of blood, i.e., blood oxygen, white blood cell, lymphocytes, neutrophils, C-reactive protein, hypersensitive C-reactive protein, and erythrocyte sedimentation rate. The final model showed good discrimination on the independent validation cohort, with an accuracy of 89.83%, sensitivity of 94.22%, specificity of 85.44%, and AUC of 0.940. This proved that the radiomics features were highly distinguishable, and this SVM model can effectively identify and diagnose patients with COVID-19 and other pneumonias. The correlation analysis results showed that some textural features were positively correlated with WBC, and NE, and also negatively related to SPO2H and NE. Our results showed that radiomic features can classify COVID-19 patients and other pneumonias patients. The SVM model can achieve an excellent diagnosis of COVID-19.

Two Novel Pathogenic Variants of TJP2 Gene and the Underlying Molecular Mechanisms in Progressive Familial Intrahepatic Cholestasis Type 4 Patients.

Progressive familial intrahepatic cholestasis (PFIC) is an autosomal recessive inherited disease that accounts for 10%-15% childhood cholestasis and could lead to infant disability or death. There are three well-established types of PFIC (1-3), caused by mutations in the ATP8B1, ABCB11, and ABCB4 genes. Biallelic pathogenic variants in the tight junction protein 2 gene (TJP2) were newly reported as a cause for PFIC type 4; however, only a limited number of patients and undisputable variants have been reported for TJP2, and the underlying mechanism for PFIC 4 remains poorly understood. To explore the diagnostic yield of TJP2 analysis in suspected PFIC patients negative for the PFIC1-3 mutation, we designed a multiplex polymerase chain reaction-based next-generation sequencing method to analyze TJP2 gene variants in 267 PFIC patients and identified biallelic rare variants in three patients, including three known pathogenic variants and two novel variants in three patients. By using CRISPR-cas9 technology, we demonstrated that TJP2 c.1202A > G was pathogenic at least partially by increasing the expression and nuclear localization of TJP2 protein. With the minigene assay, we showed that TJP2 c.2668-11A > G was a new pathogenic variant by inducing abnormal splicing of TJP2 gene and translation of prematurely truncated TJP2 protein. Furthermore, knockdown of TJP2 protein by siRNA technology led to inhibition of cell proliferation, induction of apoptosis, dispersed F-actin, and disordered microfilaments in LO2 and HepG2celles. Global gene expression profiling of TJP2 knockdown LO2 cells and HepG2 cells identified the dysregulated genes involved in the regulation of actin cytoskeleton. Microtubule cytoskeleton genes were significantly downregulated in TJP2 knockdown cells. The results of this study demonstrate that TJP2 c.1202A > G and TJP2 c.2668-11A > G are two novel pathogenic variants and the cytoskeleton-related functions and pathways might be potential molecular pathogenesis for PFIC.

Regional Neural Activity Changes in Parkinson's Disease-Associated Mild Cognitive Impairment and Cognitively Normal Patients.

PURPOSE: The aim of this study was to compare regional homogeneity (ReHo) changes in Parkinson's disease mild cognitive impairment (PD-MCI) patients with respect to normal controls (NC) and those with cognitively normal PD (PD-CN). Further, the study investigated the relationship between ReHo changes in PD patients and neuropsychological variation. PATIENTS AND METHODS: Thirty PD-MCI, 19 PD-CN, and 21 NC subjects were enrolled. Resting state functional magnetic resonance imaging data of all subjects were collected, and regional brain activity was measured for ReHo. Analysis of covariance for ReHo was determined between the PD-MCI, PD-CN, and NC groups. Spearman rank correlations were assessed using the ReHo maps and data from the neuropsychological tests. RESULTS: In comparison with NC, PD-CN patients showed significantly higher ReHo values in the right middle frontal gyrus (MFG) and lower ReHo values in the left supramarginal gyrus, bilateral inferior parietal lobule (IPL), and the right postcentral gyrus (PCG). In comparison with PD-CN patients, PD-MCI patients displayed significantly higher ReHo values in the right PCG, left middle occipital gyrus (MOG) and IPL. No significant correlation between ReHo indices and the neuropsychological scales was observed. CONCLUSION: Our finding revealed that decreases in ReHo in the default mode network (DMN) may appear before PD-related cognitive impairment. In order to preserve executive attention capacity, ReHo in the right MFG in PD patients lacking cognition impairment increased for compensation. PD-MCI showed increased ReHo in the left MOG, which might have been caused by visual and visual-spatial dysfunction, and increased ReHo in the left IPL, which might reflect network disturbance and induce cognition deficits.