Phylogeny and evolution of dissimilatory sulfite reduction in prokaryotes.

Sulfate is the second most common nonmetallic ion in modern oceans, as its concentration dramatically increased alongside tectonic activity and atmospheric oxidation in the Proterozoic. Microbial sulfate/sulfite metabolism, involving organic carbon or hydrogen oxidation, is linked to sulfur and carbon biogeochemical cycles. However, the coevolution of microbial sulfate/sulfite metabolism and Earth's history remains unclear. Here, we conducted a comprehensive phylogenetic analysis to explore the evolutionary history of the dissimilatory sulfite reduction (Dsr) pathway. The phylogenies of the Dsr-related genes presented similar branching patterns but also some incongruencies, indicating the complex origin and evolution of Dsr. Among these genes, dsrAB is the hallmark of sulfur-metabolizing prokaryotes. Our detailed analyses suggested that the evolution of dsrAB was shaped by vertical inheritance and multiple horizontal gene transfer events and that selection pressure varied across distinct lineages. Dated phylogenetic trees indicated that key evolutionary events of dissimilatory sulfur-metabolizing prokaryotes were related to the Great Oxygenation Event (2.4-2.0 Ga) and several geological events in the "Boring Billion" (1.8-0.8 Ga), including the fragmentation of the Columbia supercontinent (approximately 1.6 Ga), the rapid increase in marine sulfate (1.3-1.2 Ga), and the Neoproterozoic glaciation event (approximately 1.0 Ga). We also proposed that the voluminous iron formations (approximately 1.88 Ga) might have induced the metabolic innovation of iron reduction. In summary, our study provides new insights into Dsr evolution and a systematic view of the coevolution of dissimilatory sulfur-metabolizing prokaryotes and the Earth's environment.

Running exercise decreases microglial activation in the medial prefrontal cortex in an animal model of depression.

BACKGROUND: Running exercise effectively ameliorates depressive symptoms in humans and depression-like behaviors in animals, but the underlying mechanisms remain unclear. Microglia-mediated neuroinflammation plays a major role in the development of depression. The medial prefrontal cortex (mPFC) is a key brain region involved in depression and is sensitive to physical activity. Whether the antidepressant effect of running exercise involves changes in mPFC microglia is not understood. METHODS: The animals were subjected to chronic unpredictable stress (CUS) intervention followed by treadmill running. The sucrose preference test and elevated plus maze test or tail suspension test were used for behavioral assessment of the animals. The number of microglia in the mPFC was quantified by immunohistochemistry and stereology. The density and morphology of microglia were analyzed via immunofluorescence staining combined with three-dimensional laser scanning techniques. The mRNA expressions of inflammatory cytokines in the mPFC were examined via quantitative real-time PCR. RESULTS: Running exercise effectively alleviated depressive-like behaviors in depression model animals. Running exercise reversed the increase in the number of microglia and the density of activated microglia in the mPFC of CUS animals. Running exercise effectively reversed the changes in microglia (reduced cell body area, total branch length and branch complexity) in the mPFC of CUS animals. Furthermore, running exercise regulated the gene expressions of pro-/antiinflammatory cytokines in the mPFC of CUS animals. CONCLUSIONS: Our results suggested that the antidepressant effects of running exercise may involve decreasing the number of activated microglia, reversing morphological changes in microglia in the mPFC, and reducing inflammatory responses.

Characterization of the prevalence of Salmonella in different retail chicken supply modes using genome-wide and machine-learning analyses.

Salmonella is a foodborne pathogen that causes salmonellosis, of which retail chicken meat is a major source. However, the prevalence of Salmonella in different retail chicken supply modes and the threat posed to consumers remains unclear. The prevalence, serotype distribution, antibiotic resistance, and genomic characteristics of Salmonella in three supply modes of retail chicken (live poultry, frozen, and chilled) were investigated using whole-genome sequencing (WGS) and machine learning (ML). In this study, 480 retail chicken samples from live poultry, frozen, and chilled supply modes in Guangzhou from 2020 to 2021, as well as 253 Salmonella isolates (total isolation rate = 53.1 %), were collected. The prevalence of isolates in the live poultry mode (67.5 %, 81/120) was statistically higher than in the frozen (50.0 %, 120/240) and chilled (43.3 %, 52/120) (P < 0.05) modes. Serotype identification showed significant differences in the serotype distribution of Salmonella in different supply modes. S. Enteritis (46.7 %) and S. Indiana (14.2 %) were predominant in the frozen mode. S. Agona (23.5 %) and S. Saintpaul (13.6 %) were predominant in live poultry, while S. Enteritis (40.4 %) and S. Kentucky (17.3 %) were predominant in chilled mode. Antibiotic testing showed that frozen mode isolates were more resistant; the multidrug-resistant (MDR) rate of isolates in the frozen mode reached 91.8 %, significantly higher than in the chilled (86.5 %) and live (74.1 %) (P < 0.05) modes. WGS was performed on 155 top serotypes (S. Enteritidis, S. Kentucky, S. Indiana, and S. Agona). The antibiotic resistance gene analysis showed that the abundance and carrying rate of antibiotic resistance genes of Salmonella in the frozen mode (54 types, 16.1 %) were significantly higher than in other modes (live poultry: 36 types, 9.4 %, P < 0.05; chilled: 31 types, 11.6 %). The blaNDM-1 and blaNDM-9 genes encoding carbapenem resistance were found in frozen mode isolates on a complex transposon consisting of TnAS3-IS26. Virulence factors and plasmid replicons were abundant in the studied frozen mode isolates. In addition, single nucleotide polymorphism (SNP) phylogenetic tree results showed that in the frozen supply mode, the S. Enteritidis clonal clade continued to contaminate retail chicken meat and was homologous to S. Enteritidis strains found in farm chicken embryos, slaughterhouse chicken carcasses, and patients from hospitals in China (SNP 0 = 10). Notably, the pan-genome-based ML model showed that characteristic genes in frozen and live poultry isolates differed. The narZ gene was a key characteristic gene in frozen isolates, encoding nitrate reductase, relating to anaerobic bacterial growth. The ydgJ gene is a key characteristic gene in the live mode and encodes an oxidoreductase related to oxidative function in bacteria. The high prevalence of live poultry mode Salmonella and the transmission of frozen mode MDR Salmonella in this study pose serious risks to food safety and public health, emphasizing the importance of improving disinfection and cold storage measures to reduce Salmonella contamination and transmission. In conclusion, the continued surveillance of Salmonella across different supply models and the development of an epidemiological surveillance system based on WGS is necessary.

A convenient broad-host counterselectable system endowing rapid genetic manipulations of Kluyveromyces lactis and other yeast species.

Being generally regarded as safe, Kluyveromyces lactis has been widely taken for food, feed, and pharmaceutical applications, owing to its ability to achieve high levels of protein secretion and hence being suitable for industrial production of heterologous proteins. Production platform strains can be created through genetic engineering; while prototrophic cells without chromosomally accumulated antibiotics resistance genes have been generally preferred, arising the need for dominant counterselection. We report here the establishment of a convenient counterselection system based on a Frs2 variant, Frs2v, which is a mutant of the alpha-subunit of phenylalanyl-tRNA synthase capable of preferentially incorporating a toxic analog of phenylalanine, r-chloro-phenylalanine (4-CP), into proteins to bring about cell growth inhibition. We demonstrated that expression of Frs2v from an episomal plasmid in K. lactis could make the host cells sensitive to 2 mM 4-CP, and a Frs2v-expressing plasmid could be efficiently removed from the cells immediately after a single round of cell culturing in a 4-CP-contianing YPD medium. This Frs2v-based counterselection helped us attain scarless gene replacement in K. lactis without any prior engineering of the host cells. More importantly, counterselection with this system was proven to be functionally efficient also in Saccharomyces cerevisiae and Komagataella phaffii, suggestive of a broader application scope of the system in various yeast hosts. Collectively, this work has developed a strategy to enable rapid, convenient, and high-efficiency construction of prototrophic strains of K. lactis and possibly many other yeast species, and provided an important reference for establishing similar methods in other industrially important eukaryotic microbes.

PGC-1α in the hippocampus mediates depressive-like and stress-coping behaviours and regulates excitatory synapses in the dentate gyrus in mice.

Decreased hippocampal synaptic plasticity is an important pathological change in stress-related mood disorders, including major depressive disorder. However, the underlying mechanism is unclear. PGC-1α, a transcriptional coactivator, is a key factor in synaptic plasticity. We investigated the relationships between changes in hippocampal PGC-1α expression and depressive-like and stress-coping behaviours, and whether they are related to hippocampal synapses. Adeno-associated virus was used to alter hippocampal PGC-1α expression in male C57BL/6 mice. The sucrose preference test and forced swimming test were used to assess their depressive-like and stress-coping behaviours, respectively. Immunohistochemistry and stereology were used to calculate the total number of excitatory synapses in each hippocampal subregion (the cornu ammonis (CA) 1, CA3, and dentate gyrus). Immunofluorescence was used to visualize the changes in dendritic structure. Western blotting was used to detect the expression of hippocampal PGC-1α and mitochondrial-associated proteins, such as UCP2, NRF1 and mtTFAs. Our results showed that mice with downregulated PGC-1α expression in the hippocampus exhibited depressive-like and passive stress-coping behaviours, while mice with upregulated PGC-1α in the hippocampus exhibited increased stress-coping behaviours. Moreover, the downregulation of hippocampal PGC-1α expression resulted in a decrease in the number of excitatory synapses in the DG and in the protein expression of UCP2 in the hippocampus. Alternatively, upregulation of hippocampal PGC-1α yielded the opposite results. This suggests that hippocampal PGC-1α is involved in regulating depressive-like and stress-coping behaviours and modulating the number of excitatory synapses in the DG. This provides new insight for the development of antidepressants.

Running exercise improves astrocyte loss, morphological complexity and astrocyte-contacted synapses in the hippocampus of CUS-induced depression model mice.

Although the antidepressant effects of running exercise have been widely reported, further research is still needed to determine the structural bases for these effects. Astrocyte processes physically contact many synapses and directly regulate the numbers of synapses, but it remains unclear whether running exercise can modulate astrocyte morphological complexity and astrocyte-contacted synapses in the hippocampus of the mice with depressive-like behavior. Male C57BL/6 J mice underwent four weeks of running exercise after four weeks of chronic unpredictable stress (CUS). The sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST) were used to assess anhedonia in mice. Western blotting was used to measure the expression of astrocyte- and synapse-related proteins. Immunofluorescence and 3D reconstruction were used to quantify the density and morphology of astrocytes, and astrocyte-contacted synapses in each hippocampal subregion. Four weeks of running exercise alleviated depressive-like symptoms in mice. The expression of astrocyte- and synapse-related proteins in the hippocampus; astrocyte process lengths, process numbers, and dendritic arborization; and the number of astrocyte-contacted PSD95 positive synapses in the CA2-3 and DG regions were significantly decreased in the mice with depressive-like behavior, and running exercise successfully reserved these changes. Running exercise improved the decreases in astrocyte morphological complexity and astrocyte-contacted PSD95 positive synapses in the CA2-3 and DG regions of the mice with depressive-like behavior, suggesting that the physical interactions between astrocytes and synapses can be increased by running exercise, which might be an important structural basis for the antidepressant effects of running exercise.

Running exercise alleviates hippocampal neuroinflammation and shifts the balance of microglial M1/M2 polarization through adiponectin/AdipoR1 pathway activation in mice exposed to chronic unpredictable stress.

Running exercise has been shown to alleviate depressive symptoms. However, the mechanism underlying the antidepressant effects of running exercise is not fully understood. The imbalance of M1/M2 microglia phenotype/polarization and concomitant dysregulation of neuroinflammation play crucial roles in the pathogenesis of depression. Running exercise increases circulating levels of adiponectin which is known to cross the blood‒brain barrier and suppress inflammatory responses. AdipoR1 is an adiponectin receptor that is involved in regulating microglial phenotypes and activation states. However, whether running exercise regulates hippocampal microglial phenotypes and neuroinflammation through adiponectin/AdipoR1 to exert its antidepressant effects remains unclear. In the current study, 4 weeks of running exercise significantly alleviated the depressive-like behaviors of chronic unpredictable stress (CUS)-exposed mice. Moreover, running exercise decreased the microglial numbers and altered microglial morphology in three subregions of the hippocampus to restore the M1/M2 balance; these effects were accompanied by regulation of pro-/anti-inflammatory cytokine production and secretion in CUS-exposed mice. These effects may involve elevation of peripheral tissue (adipose tissue and muscle) and plasma adiponectin levels, and hippocampal AdipoR1 levels as well as activation of the AMPK-NF-κB/STAT3 signaling pathway by running exercise. When an adeno-associated virus was used to knock down hippocampal AdipoR1, mice showed depressive-like behaviors and alterations in microglia and inflammatory factor expression in the hippocampus that were similar to those observed in CUS-exposed mice. Together, these results suggest that running exercise maintains the M1/M2 balance and inhibits neuroinflammation in the hippocampus of CUS-exposed mice. These effects might occur via adiponectin/AdipoR1-mediated activation of the AMPK-NF-κB/STAT3 signaling pathway.

VSG-GAN: A high-fidelity image synthesis method with semantic manipulation in retinal fundus image.

In recent years, advancements in retinal image analysis, driven by machine learning and deep learning techniques, have enhanced disease detection and diagnosis through automated feature extraction. However, challenges persist, including limited data set diversity due to privacy concerns and imbalanced sample pairs, hindering effective model training. To address these issues, we introduce the vessel and style guided generative adversarial network (VSG-GAN), an innovative algorithm building upon the foundational concept of GAN. In VSG-GAN, a generator and discriminator engage in an adversarial process to produce realistic retinal images. Our approach decouples retinal image generation into distinct modules: the vascular skeleton and background style. Leveraging style transformation and GAN inversion, our proposed hierarchical variational autoencoder module generates retinal images with diverse morphological traits. In addition, the spatially adaptive denormalization module ensures consistency between input and generated images. We evaluate our model on MESSIDOR and RITE data sets using various metrics, including structural similarity index measure, inception score, Fréchet inception distance, and kernel inception distance. Our results demonstrate the superiority of VSG-GAN, outperforming existing methods across all evaluation assessments. This underscores its effectiveness in addressing data set limitations and imbalances. Our algorithm provides a novel solution to challenges in retinal image analysis by offering diverse and realistic retinal image generation. Implementing the VSG-GAN augmentation approach on downstream diabetic retinopathy classification tasks has shown enhanced disease diagnosis accuracy, further advancing the utility of machine learning in this domain.

Preoperative evaluation of microvascular invasion in hepatocellular carcinoma with a radiological feature-based nomogram: a bi-centre study.

PURPOSE: To develop a nomogram for preoperative assessment of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) based on the radiological features of enhanced CT and to verify two imaging techniques (CT and MRI) in an external centre. METHOD: A total of 346 patients were retrospectively included (training, n = 185, CT images; external testing 1, n = 90, CT images; external testing 2, n = 71, MRI images), including 229 MVI-negative patients and 117 MVI-positive patients. The radiological features and clinical information of enhanced CT images were analysed, and the independent variables associated with MVI in HCC were determined by logistic regression analysis. Then, a nomogram prediction model was constructed. External validation was performed on CT (n = 90) and MRI (n = 71) images from another centre. RESULTS: Among the 23 radiological and clinical features, size, arterial peritumoral enhancement (APE), tumour margin and alpha-fetoprotein (AFP) were independent influencing factors for MVI in HCC. The nomogram integrating these risk factors had a good predictive effect, with AUC, specificity and sensitivity values of 0.834 (95% CI: 0.774-0.895), 75.0% and 83.5%, respectively. The AUC values of external verification based on CT and MRI image data were 0.794 (95% CI: 0.700-0.888) and 0.883 (95% CI: 0.807-0.959), respectively. No statistical difference in AUC values among training set and testing sets was found. CONCLUSION: The proposed nomogram prediction model for MVI in HCC has high accuracy, can be used with different imaging techniques, and has good clinical applicability.

Diagnostic accuracy of MRI for assessing lymphovascular space invasion in endometrial carcinoma: a meta-analysis.

BACKGROUND: The lymphovascular space invasion (LVSI) status of endometrial cancer (EC) has guiding significance in lymph node dissection. However, LVSI can only be obtained after surgery. Researchers have tried to extract the information of LVSI using magnetic resonance imaging (MRI). PURPOSE: To evaluate the ability of preoperative MRI to predict the LVSI status of EC. MATERIAL AND METHODS: A search was conducted by using the PubMed/MEDLINE, EMBASE, Web of Science, and the Cochrane Library databases. Articles were included according to the criteria. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2. A bivariate random effects model was used to obtain pooled summary estimates, heterogeneity, and the area under the summary receiver operating characteristic curve (AUC). A subgroup analysis was performed to identify sources of heterogeneity. RESULTS: A total of nine articles (814 patients) were included. The risk of bias was low or unclear for most studies, and the applicability concerns were low or unclear for all studies. The summary AUC values as well as pooled sensitivity and specificity of LVSI status in EC were 0.82, 73%, and 77%, respectively. According to the subgroup analysis, radiomics/non-radiomics features, country/region, sample size, age, MR manufacturer, magnetic field, scores of risk bias, and scores of applicability concern may have caused heterogeneity. CONCLUSION: Our meta-analysis showed that MRI has moderate diagnostic efficacy for LVSI status in EC. Large-sample, uniformly designed studies are needed to verify the true value of MRI in assessing LVSI.

Antagonizing LINGO-1 reduces activated microglia and alleviates dendritic spine loss in the hippocampus of APP/PS1 transgenic mice.

In Alzheimer's disease (AD), microglia are involved in synaptic pruning and mediate synapse loss. LINGO-1 is a negative regulator of nerve growth, and whether antagonizing LINGO-1 can attenuate synaptic pruning by microglia and rescue dendritic spines in the hippocampus in AD is still unclear. On this basis, the anti-LINGO-1 antibody, which binds to LINGO-1 protein and antagonizes the effects of LINGO-1, was administered to 10-month-old APP/PS1 transgenic mice for 2 months. The Morris water maze test, immunohistochemical and stereological methods, immunofluorescence and 3D reconstruction were used. Compared to wild-type mice, APP/PS1 transgenic mice had worse performance on behavioral tests, fewer dendritic spines but more microglia in the hippocampus. Meanwhile, the microglia in APP/PS1 transgenic mice had more branches of medium length (4-6 µm) and a cell body area with greater variability. Moreover, APP/PS1 transgenic mice had more postsynaptic termini colocalized with microglia in the hippocampus than wild-type mice. The anti-LINGO-1 antibody significantly reversed these changes in AD, indicating that the anti-LINGO-1 antibody can improve hippocampus-dependent learning and memory abilities and effectively rescue dendritic spines in the hippocampus of AD mice and that microglia might participate in this progression in AD. These results provide a scientific basis for further studying the mechanism of the anti-LINGO-1 antibody in AD and help to elucidate the role of LINGO-1 in the treatment of AD.

Identification of DNA Damage Repair Gene Signature as a Novel Prognostic Marker in Glioblastoma Multiforme.

BACKGROUND: The efficacy of treatment of glioblastoma multiforme (GBM) is limited. The effect of DNA damage repair is an important factor. METHODS: Expression data were downloaded from The Cancer Genome Atlas (training dataset) and the Gene Expression Omnibus (validation dataset) databases. Univariate Cox regression analysis and the least absolute shrinkage and selection operator were used to construct a DNA damage response (DDR) gene signature. Receiver operating characteristic curve analysis and Kaplan-Meier curve analysis were used to estimate the prognostic value of the risk signature. Moreover, consensus clustering analysis was used to investigate the potential subtypes of GBM according to DDR expression. RESULTS: We constructed a 3-DDR-related gene signature through the survival analysis. The Kaplan-Meier curve analysis suggested that patients in the low-risk group have significantly better survival outcomes compared with the high-risk group in the training and external validation datasets. The results from the receiver operating characteristic curve analysis indicated that the risk model has high prognostic value in the training and external validation datasets. Moreover, 3 stable molecular subtypes were identified and validated in the Gene Expression Omnibus and The Cancer Genome Atlas databases according to the expression of the DNA repair gene. The microenvironment and immunity of GBM were further investigated and showed that cluster 2 had higher immunity and a higher immune score compared with clusters 1 and 3. CONCLUSIONS: The DNA damage repair-related gene signature was an independent and powerful prognostic biomarker in GBM. Knowledge of the GBM subtypes could have important implications in the subclassification of GBM.

Qualitative and quantitative wall enhancement associated with unstable intracranial aneurysms: a meta-analysis.

BACKGROUND: Unstable intracranial aneurysms (UIAs) are more likely to rupture and cause serious consequences. Evaluating the stability of unruptured aneurysms facilitates clinical management stratification. PURPOSE: To compare and evaluate the predictive performance of qualitative and quantitative wall enhancement (aneurysmal wall enhancement [AWE], circumferential aneurysmal wall enhancement [CAWE], wall enhancement ratio [WER]) on high-resolution magnetic resonance imaging (MRI) of the vessel wall to predict the presence of UIA. MATERIAL AND METHODS: Original articles describing the depiction of aneurysmal wall enhancement on 3.0-T or 1.5-T high-resolution vessel wall imaging were retrieved from the Web of Science, Medline/PubMed, the Cochrane Library, and EMBASE databases up to 15 February 2022. The combined sensitivity, specificity, and summary area under the receiver operating characteristic curve (AUC) were calculated, and meta-regression analysis was performed. RESULTS: In total, 12 original articles involving 1619 intracranial aneurysms (IAs) were included. The combined sensitivity and specificity of AWE, CAWE, and WER were 91% and 67%, 59% and 83%, and 86% and 75%, respectively, in the diagnosis of UIA. The summary AUC values of these items were, in order from high to low, 0.88 (WER), 0.84 (AWE), and 0.77 (CAWE), and the differences among them were significant (z = 2.976, P = 0.003 and z = 2.950, P = 0.003). The meta-regression analysis identified average size and 2D/3D magnetic imaging technology as possible sources of heterogeneity. CONCLUSION: Qualitative and quantitative wall enhancement showed moderate accuracy in predicting UIA, and WER had the highest accuracy among them in this meta-analysis. Two covariates were found to explain the heterogeneity.

Analysis of clinical predictors of kidney diseases in type 2 diabetes patients based on machine learning.

BACKGROUND: The heterogeneity of Type 2 Diabetes Mellitus (T2DM) complicated with renal diseases has not been fully understood in clinical practice. The purpose of the study was to propose potential predictive factors to identify diabetic kidney disease (DKD), nondiabetic kidney disease (NDKD), and DKD superimposed on NDKD (DKD + NDKD) in T2DM patients noninvasively and accurately. METHODS: Two hundred forty-one eligible patients confirmed by renal biopsy were enrolled in this retrospective, analytical study. The features composed of clinical and biochemical data prior to renal biopsy were extracted from patients' electronic medical records. Machine learning algorithms were used to distinguish among different kidney diseases pairwise. Feature variables selected in the developed model were evaluated. RESULTS: Logistic regression model achieved an accuracy of 0.8306 ± 0.0057 for DKD and NDKD classification. Hematocrit, diabetic retinopathy (DR), hematuria, platelet distribution width and history of hypertension were identified as important risk factors. Then SVM model allowed us to differentiate NDKD from DKD + NDKD with accuracy 0.8686 ± 0.052 where hematuria, diabetes duration, international normalized ratio (INR), D-Dimer, high-density lipoprotein cholesterol were the top risk factors. Finally, the logistic regression model indicated that DD-dimer, hematuria, INR, systolic pressure, DR were likely to be predictive factors to identify DKD with DKD + NDKD. CONCLUSION: Predictive factors were successfully identified among different renal diseases in type 2 diabetes patients via machine learning methods. More attention should be paid on the coagulation factors in the DKD + NDKD patients, which might indicate a hypercoagulable state and an increased risk of thrombosis.

Can a proposed double branch multimodality-contribution-aware TripNet improve the prediction performance of the microvascular invasion of hepatocellular carcinoma based on small samples?

Objectives: To evaluate the potential improvement of prediction performance of a proposed double branch multimodality-contribution-aware TripNet (MCAT) in microvascular invasion (MVI) of hepatocellular carcinoma (HCC) based on a small sample. Methods: In this retrospective study, 121 HCCs from 103 consecutive patients were included, with 44 MVI positive and 77 MVI negative, respectively. A MCAT model aiming to improve the accuracy of deep neural network and alleviate the negative effect of small sample size was proposed and the improvement of MCAT model was verified among comparisons between MCAT and other used deep neural networks including 2DCNN (two-dimentional convolutional neural network), ResNet (residual neural network) and SENet (squeeze-and-excitation network), respectively. Results: Through validation, the AUC value of MCAT is significantly higher than 2DCNN based on CT, MRI, and both imaging (P < 0.001 for all). The AUC value of model with single branch pretraining based on small samples is significantly higher than model with end-to-end training in CT branch and double branch (0.62 vs 0.69, p=0.016, 0.65 vs 0.83, p=0.010, respectively). The AUC value of the double branch MCAT based on both CT and MRI imaging (0.83) was significantly higher than that of the CT branch MCAT (0.69) and MRI branch MCAT (0.73) (P < 0.001, P = 0.03, respectively), which was also significantly higher than common-used ReNet (0.67) and SENet (0.70) model (P < 0.001, P = 0.005, respectively). Conclusion: A proposed Double branch MCAT model based on a small sample can improve the effectiveness in comparison to other deep neural networks or single branch MCAT model, providing a potential solution for scenarios such as small-sample deep learning and fusion of multiple imaging modalities.

Diagnostic Accuracy of the Apparent Diffusion Coefficient for Microvascular Invasion in Hepatocellular Carcinoma: A Meta-analysis.

Background and Aims: Microvascular invasion (MVI) is a major risk factor for the early recurrence of hepatocellular carcinoma (HCC) and it seriously worsens the prognosis. Accurate preoperative evaluation of the presence of MVI could greatly benefit the treatment management and prognosis prediction of HCC patients. The study aim was to evaluate the diagnostic performance of the apparent diffusion coefficient (ADC), a quantitative parameter for the preoperative diagnosis MVI in HCC patients. Methods: Original articles about diffusion-weighted imaging (DWI) and/or intravoxel incoherent motion (IVIM) conducted on a 3.0 or 1.5 Tesla magnetic resonance imaging (MRI) system indexed through January 17, 2021were collected from MEDLINE/PubMed, Web of Science, EMBASE, and the Cochrane Library. Methodological quality was evaluated using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). The pooled sensitivity, specificity, and summary area under the receiver operating characteristic curve (AUROC) were calculated, and meta-regression analysis was performed using a bivariate random effects model through a meta-analysis. Results: Nine original articles with a total of 988 HCCs were included. Most studies had low bias risk and minimal applicability concerns. The pooled sensitivity, specificity and AUROC of the ADC value were 73%, 70%, and 0.78, respectively. The time interval between the index test and the reference standard was identified as a possible source of heterogeneity by subgroup meta-regression analysis. Conclusions: Meta-analysis showed that the ADC value had moderate accuracy for predicting MVI in HCC. The time interval accounted for the heterogeneity.

Positive effects of running exercise on astrocytes in the medial prefrontal cortex in an animal model of depression.

Depression is one of the most common mental illnesses and seriously affects all aspects of life. Running exercise has been suggested to prevent or alleviate the occurrence and development of depression; however, the underlying mechanisms of these effects remain unclear. Independent studies have indicated that astrocytes play essential roles and that the medial prefrontal cortex (mPFC) is an important brain region involved in the pathology underlying depression. However, it is unknown whether running exercise achieves antidepressant effects by affecting the number of astrocytes and glutamate transport function in the mPFC. Here, animal models of depression were established using chronic unpredictable stress (CUS), and depression-like behavior was assessed by the sucrose preference test. After successfully establishing the depression model, experimental animals performed running exercise. Glial fibrillary acidic protein-positive (GFAP+ ) cell number in the mPFC was precisely quantified using immunohistochemical and stereological methods, and the densities of bromodeoxyuridine-positive (BrdU+ ) and BrdU+ /GFAP+ cells in the mPFC were measured using a semiquantitative immunofluorescence assay. Changes in glutamate transporter gene expression in mPFC astrocytes were detected by mRNA sequencing and qRT-PCR. We found that running exercise reversed CUS-induced decreases in sucrose preference, increased astrocyte number and the density of newborn astrocytes, and reversed decreases in gene expression levels of GFAP, S100b, and the glutamate transporters GLT-1 and GLAST in the mPFC of CUS animals. These results suggested that changes in astrocyte number and glutamate transporter function may be potential meditators of the effects of running exercise in the treatment of depression.

Activation of liver X receptors protects oligodendrocytes in CA3 of stress-induced mice.

Depression is a complex disorder that is associated with various structural abnormalities. Oligodendrocyte (OL) dysfunction is associated with the pathogenesis of depression and the promotion of hippocampal oligodendrocyte maturation and myelination could be a novel therapeutic strategy for ameliorating depressive behaviors. Recent studies have shown that activation of liver X receptors (LXRs) by GW3965 improves depressive phenotypes, but the effects of GW3965 on OL function and myelination in the hippocampus of depression remain relatively unclear. To address this issue, we investigated the effects of GW3965 on mature OL in the hippocampus and on the myelin sheaths of mice subjected to chronic unpredictable stress (CUS). Behavioral tests were performed to assess depressive behaviors. Then, the number of mature OLs (CC1+) in each hippocampal subregion was precisely quantified with immunohistochemical and stereological methods, and the density of newborn mature OLs (BrdU+/Olig2+/CC1+ cells) in each hippocampal subregion was quantified with immunofluorescence. In addition, myelin basic protein (MBP) staining intensity in the cornu ammonis 3 (CA3) region was assessed by using immunofluorescence. We found that both the number of CC1+ OLs and the density of BrdU+/Olig2+/CC1+ cells were obviously decreased in each hippocampal subregion of mice subjected to CUS, and 4 weeks of GW3965 treatment reversed these effects only in the CA3 region. Furthermore, the decreased MBP expression in the CA3 region of mice subjected to CUS was ameliorated by GW3965 treatment. Collectively, these results suggested that improvement of OL maturation and enhancement of myelination may be structural mechanisms underlying the antidepressant effects of LXR agonists.

Intraosseous Hemangioma of the Ethmoid Sinus: A Case Report.

Intraosseous hemangiomas usually occur in the vertebrae and skull bones, whereas those arising within the nasal cavity are exceedingly rare. Here, we describe the case of a 40-year-old woman with nasal congestion who presented to our hospital with a tumor located in the left nasal cavity. Unenhanced paranasal computed tomography revealed an approximately 3 cm large mass originating from the anterior wall of the ethmoid sinus. Pre-operative imaging failed to reveal the etiology of the mass. The tumor was successfully resected using a trans-nasal endoscopic approach without pre-operative embolization. No complications occurred during the post-operative period, and there was no evidence of recurrence at the 3-month and 6-month follow-up. Histological examination of the resected specimen showed endothelium-lined blood-filled vascular spaces within the bony trabecule, suggesting a pattern typical of intraosseous cavernous hemangioma. Thus, although intraosseous hemangiomas of the nasal cavity are extremely rare, they must be considered when a bony mass is detected in the nasal cavity.