Search

Abstract The process of chemical exchange saturation transfer (CEST) is quantified by evaluating a Z-spectra, where CEST signal quantification and Z-spectra fitting have been widely used to distinguish the contributions from multiple origins. Based on the exchange-dependent relaxation rate in the rotating frame (R ex), this paper introduces an additional pathway to quantitative separation of CEST effect. The proposed R ex-line-fit method is solved by a multi-pool model and presents the advantage of only being dependent of the specific parameters (solute concentration, solute‐water exchange rate, solute transverse relaxation, and irradiation power). Herein we show that both solute‐water exchange rate and solute concentration monotonously vary with R ex for Amide, Guanidino, NOE and MT, which has the potential to assist in solving quantitative separation of CEST effect. Furthermore, we achieve R ex imaging of Amide, Guanidino, NOE and MT, which may provide direct insight into the dependency of measurable CEST effects on underlying parameters such as the exchange rate and solute concentration, as well as the solute transverse relaxation.

Abstract The brain presents age-related structural and functional changes in the human life, with different extends between subjects and groups. Brain age prediction can be used to evaluate the development and aging of human brain, as well as providing valuable information for neurodevelopment and disease diagnosis. Many contributions have been made for this purpose, resorting to different machine learning methods. To solve this task and reduce memory resource consumption, we develop a mini architecture of only 10 layers by modifying the deep residual neural network (ResNet), named ResNet mini architecture. To support the ResNet mini architecture in brain age prediction, the brain age dataset (OpenNeuro #ds000228) that consists of 155 study participants (three classes) and the Alzheimer MRI preprocessed dataset that consists of 6400 images (four classes) are employed. We compared the performance of the ResNet mini architecture with other popular networks using the two considered datasets. Experimental results show that the proposed architecture exhibits generality and robustness with high accuracy and less parameter number.

Despite the observed decrease in liver fat associated with metabolic-associated fatty liver disease (MAFLD) in mice following fecal microbiota transplantation, the clinical effects and underlying mechanisms of washed microbiota transplantation (WMT), a refined method of fecal microbiota transplantation, for the treatment of MAFLD remain unclear. In this study, both patients and mice with MAFLD exhibit an altered gut microbiota composition. WMT increases the levels of beneficial bacteria, decreases the abundance of pathogenic bacteria, and reduces hepatic steatosis in MAFLD-affected patients and mice. Downregulation of the liver-homing chemokine receptor CXCR6 on ILC3s results in an atypical distribution of ILC3s in patients and mice with MAFLD, characterized by a significant reduction in ILC3s in the liver and an increase in ILC3s outside the liver. Moreover, disease severity is negatively correlated with the proportion of hepatic ILC3s. These hepatic ILC3s demonstrate a mitigating effect on hepatic steatosis through the release of IL-22. Mechanistically, WMT upregulates CXCR6 expression on ILC3s, thereby facilitating their migration to the liver of MAFLD mice via the CXCL16/CXCR6 axis, ultimately contributing to the amelioration of MAFLD. Overall, these findings highlight that WMT and targeting of liver-homing ILC3s could be promising strategies for the treatment of MAFLD.

Abstract Tumor‐initiating cells (TICs) resilience and an immunosuppressive microenvironment are aggressive oncogenic phenotypes that contribute to unsatisfactory long‐term outcomes in lung adenocarcinoma (LUAD) patients. The molecular mechanisms mediating the interaction between TICs and immune tolerance have not been elucidated. The role of Galectin‐9 in oncogenesis and immunosuppressive microenvironment is still unknown. This study explored the potential role of galectin‐9 in TIC regulation and immune modulation in LUAD. The results show that galectin‐9 supports TIC properties in LUAD. Co‐culture of patient‐derived organoids and matched peripheral blood mononuclear cells showed that tumor‐secreted galectin‐9 suppressed T cell cytotoxicity and induced regulatory T cells (Tregs). Clinically, galectin‐9 is upregulated in human LUAD. High expression of galectin‐9 predicted poor recurrence‐free survival and correlated with high levels of Treg infiltration. LGALS9, the gene encoding galectin‐9, is found to be transcriptionally regulated by the nuclear factor of activated T cells 2 (NFATc2), a previously reported TIC regulator, via in silico prediction and luciferase reporter assays. Overall, the results suggest that the NFATc2/galectin‐9 axis plays a dual role in TIC regulation and immune suppression.

Abstract Background The γ-aminobutyric acid (GABA) hypothesis posits a role of GABA deficiency in the central nervous system in the pathogenesis and progression of essential tremor (ET). However, the specific causative factor for GABA deficiency is not clear. The gut microbiota in mammals has recently been considered as a significant source of GABA. Furthermore, the GABA-based signals originating from the intestine can be transmitted to the brain through the “enteric nervous system–vagus nerve–brain” axis. However, the plausible contribution of gut microbiota to ET seems inspiring but remains obscure. Methods Fecal samples from patients with ET and healthy controls were examined by metagenomic sequencing to compare the composition of gut microbiota and the expression of genes involved in GABA biosynthesis. The impact of gut microbiota on ET was explored through transplantation of fecal microbiota from patients with ET into the murine ET model. Lactic acid bacteria producing high amounts of GABA were identified through whole-genome sequencing and ultra-performance liquid chromatography-tandem mass spectrometry. Subsequently, mice were treated with the high-GABA-producing strain Lactobacillus plantarum L5. Tremor severity, behavioral tests, pro-inflammatory cytokines, GABA concentration, and gut microbiota composition were examined in these mice. Results The gut microbiota of patients with ET demonstrated an impaired GABA-producing capacity and a reduced fecal GABA concentration. Transplantation of the gut microbiota from patients with ET induced an extension of tremor duration and impaired mobility in the murine model of ET. L5 exhibited an augmented GABA-producing capacity, with the De Man-Rogosa-Sharpe culture broth containing 262 mg/l of GABA. In addition, administration of L5 significantly decreased the tremor severity and enhanced the movement capability and grasping ability of ET mice. In vivo mechanistic experiments indicated that L5 reshaped the gut microbial composition, supplemented the mucosa-associated microbiota with GABA-producing capacity, increased the GABA concentrations in the cerebellum, and diminished inflammation in the central nervous system. Conclusions These findings highlight that deficiency of GABA-producing gut microbes plays an essential role in the pathogenesis of ET and that L5 is a promising candidate for treating ET.

Abstract Background Spermatogenic dysfunction is an important cause of azoospermia. Numerous studies have focused on germ-cell-related genes that lead to spermatogenic impairment. However, based on the immune-privileged characteristics of the testis, the relationship of immune genes, immune cells or immune microenvironment with spermatogenic dysfunction has rarely been reported. Results Using integrated methods including single-cell RNA-seq, microarray data, clinical data analyses and histological/pathological staining, we found that testicular mast cell infiltration levels were significantly negatively related to spermatogenic function. We next identified a functional testicular immune biomarker, CCL2, and externally validated that testicular CCL2 was significantly upregulated in spermatogenic dysfunctional testes and was negatively correlated with Johnsen scores (JS) and testicular volumes. We also demonstrated that CCL2 levels showed a significant positive correlation with testicular mast cell infiltration levels. Moreover, we showed myoid cells and Leydig cells were two of the important sources of testicular CCL2 in spermatogenic dysfunction. Mechanistically, we drew a potential “myoid/Leydig cells-CCL2-ACKR1-endothelial cells-SELE-CD44-mast cells” network of somatic cell–cell communications in the testicular microenvironment, which might play roles in spermatogenic dysfunction. Conclusions The present study revealed CCL2-relevant changes in the testicular immune microenvironment in spermatogenic dysfunction, providing new evidence for the role of immunological factors in azoospermia.

IntroductionGut microbiota and metabolites have been identified to contribute to the pathogenesis of functional constipation (FC); however, the underlying mechanism(s) have not been elucidated, and the relationship between the gut microbiota and metabolites in FC has received limited attention in the literature.Methods16S rDNA sequencing and non-targeted metabolomic detection based on liquid chromatography-mass spectrometry (LC–MS/MS) technologies were combined to analyze the altered gut microbiome and metabolic profile of fecal samples from FC patients and healthy individuals (healthy control; HC).ResultsThe richness and diversity of gut microbiota significantly (p < 0.01) increased in FC patients. Compared to the HC group, 18 genera, including Intestinibacter, Klebsiella, and Akkermansia, exhibited statistically significant changes (p < 0.05). Metabolic analysis showed that metabolic profiles were also markedly altered with 79 metabolites, such as (-)-caryophyllene oxide, chenodeoxycholic acid, and biliverdin, indicating significant inter-group differences (p < 0.05). Besides, the primary bile acid biosynthesis, as well as the metabolic profile of porphyrin and chlorophyll, were the most dominant enriched pathways (FDR < 0.01), in which chenodeoxycholic acid and biliverdin were significantly enriched, respectively. Correlation analysis demonstrated a strong relationship between 10 genera and 19 metabolites (r > 0.6, FDR < 0.05), and notably, Intestinibacter showed a negative correlation with biliverdin (FDR < 0.001), which highlighted the interplay of the gut microbiota and metabolites in the pathogenesis of FC.ConclusionOur research describes the characteristics of the gut microbiota and metabolic profiles and the correlation between the gut microbiota and metabolites in FC patients. This may contribute to the understanding of the underlying mechanisms involved in FC pathogenesis and may provide novel insights into therapeutic interventions.

Cryptotanshinone (CPT), a bioactive compound derived from the traditional Chinese herb Salvia miltiorrhiza, exhibits promising antidepressant properties. Employing a rat model subjected to Chronic Unpredictable Mild Stress (CUMS), behavioral analyses (open field experiment, elevated cross maze experiment, sugar water preference experiment, forced swimming experiment) and inflammatory factor assessments were conducted to assess the efficacy of CPT in alleviating depressive symptoms and inflammatory responses induced by CUMS. Moreover, 16 S rDNA analysis revealed alterations in the gut microbiota of rats exposed to both CUMS and CPT administration. Notably, CPT administration was found to mitigate harmful bacterial shifts associated with depression. Preliminary exploration of the molecular mechanism underlying CPT’s antidepressant effects via transcriptomics analysis and molecular docking indicated that CPT might exert its influence by regulating the PI3K-AKT pathway. This study sheds light on the potential therapeutic role of CPT in managing depressive disorders, offering a comprehensive understanding of its impact on behavior, inflammation, gut microbiota, and molecular pathways.

Objection: To investigate the potential link between aberrant mitochondrial energy metabolism mediated by the AMPK/SIRT1 pathway and the etiology of anxiety disorders. Methods: The anxiety rat model was established by uncertain empty water bottle（UEWB）stress. Rats were submitted behavioral tests on the seventh, fourteenth, and twenty-first days and had the prefrontal cortex and amygdala removed for biochemical tests. The morphological alterations of the mitochondria in the medial prefrontal cortex and amygdala were examined by using a transmission electron microscope. Expression levels of AMPK, SIRT1, PGC-1, NRF-1 and NRF-2 were tested by western-blot analysis. ATP, respiratory chain complex and caspase enzyme expressions were tested by neurochemical and biochemical assays. Results: Rats showed anxiety-like behavior after being exposed to the uncertain empty water bottle (UEWB) stress model. In model rats, mitochondrial structure is damaged, mitochondrial energy metabolism is decreased, and the expression of proteins associated with AMPK/SIRT1 pathway is significantly reduced in the brain. Conclusion: The level of mitochondrial energy metabolism correlates with anxiety-like behavior. The main mechanism of anxiety disorder is a disturbance of mitochondrial energy metabolism, which might be related to AMPK/SIRT1 pathway.

IntroductionThe ongoing 2019 coronavirus disease pandemic (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its variants, is a global public health threat. Early diagnosis and identification of SARS-CoV-2 and its variants plays a critical role in COVID-19 prevention and control. Currently, the most widely used technique to detect SARS-CoV-2 is quantitative reverse transcription real-time quantitative PCR (RT-qPCR), which takes nearly 1 hour and should be performed by experienced personnel to ensure the accuracy of results. Therefore, the development of a nucleic acid detection kit with higher sensitivity, faster detection and greater accuracy is important.MethodsHere, we optimized the system components and reaction conditions of our previous detection approach by using RT-RAA and Cas12b.ResultsWe developed a Cas12b-assisted one-pot detection platform (CDetection.v2) that allows rapid detection of SARS-CoV-2 in 30 minutes. This platform was able to detect up to 5,000 copies/ml of SARS-CoV-2 without cross-reactivity with other viruses. Moreover, the sensitivity of this CRISPR system was comparable to that of RT-qPCR when tested on 120 clinical samples.DiscussionThe CDetection.v2 provides a novel one-pot detection approach based on the integration of RT-RAA and CRISPR/Cas12b for detecting SARS-CoV-2 and screening of large-scale clinical samples, offering a more efficient strategy for detecting various types of viruses.

Abstract Glutathione S‐transferase pi (GSTP1), a phase II detoxification enzyme, is known to be overexpressed and mediates chemotherapeutic resistance in lung cancer. However, whether GSTP1 supports cancer stem cells (CSCs) and the underlying mechanisms in lung adenocarcinoma (LUAD) remain largely unknown. This study unveiled that GSTP1 is upregulated in lung CSCs and supports tumor self‐renewal, metastasis, and resistance to targeted tyrosine kinase inhibitors of LUAD both in vitro and in vivo. Mechanistically, CaMK2A (calcium/calmodulin‐dependent protein kinase 2 isoform A)/NRF2 (nuclear factor erythroid 2‐related factor 2)/GSTP1 is uncovered as a regulatory axis under hypoxia. CaMK2A increased GSTP1 expression through phosphorylating the Sersine558 residue of NRF2 and promoting its nuclear translocation, a novel mechanism for NRF2 activation apart from conventional oxidization‐dependent activation. Upregulation of GSTP1 in turn suppressed reactive oxygen species levels and supported CSC phenotypes. Clinically, GSTP1 analyzed by immunohistochemistry is upregulated in a proportion of LUAD and serves as a prognostic marker for survival. Using patient‐derived organoids from an ALK‐translocated LUAD, the therapeutic potential of a specific GSTP1 inhibitor ezatiostat in combination treatment with the ALK inhibitor crizotinib is demonstrated. This study demonstrates GSTP1 to be a promising therapeutic target for long‐term control of LUAD through targeting CSCs.

Lung cancer is a malignant tumor with high rates of mortality and shows significant hereditary predisposition. Previous genome-wide association studies suggest that rs748404, located at promoter of TGM5 (transglutaminase 5), is associated with lung carcinoma. By analysis of 1000 genomes project data for three representative populations in the world, another five SNPs are identified to be in strong linkage disequilibrium with rs748404, thus suggesting that they may also be associated with lung carcinoma risk. However, it is ambiguous about the actually causal SNP(s) and the mechanism for the association. Dual-luciferase assay indicates that the functional SNPs are not rs748404, rs12911132 or rs35535629 but another three SNPs (rs66651343, rs12909095 and rs17779494) in lung cell. By chromosome conformation capture, it is disclosed that the enhancer encompassing the two SNPs, rs66651343 and rs12909095, can interact with the promoter of CCNDBP1 (cyclin D1 binding protein 1). RNA-seq data analysis indicates that CCNDBP1 expression is dependent on the genotype of these two SNPs. Chromatin immunoprecipitation assay suggests that the fragments spanning rs66651343 and rs12909095 can bind with the transcription factors, cut like homeobox 1 and SRY-box transcription factor 9, respectively. Our results establish the connection between genetic variations at this locus and lung cancer susceptibility.

As a component of the MAP project, the study of the flora in Northeast Asia (comprising Japan, South Korea, North Korea, Northeast China, and Mongolia) convincingly underscores the indispensability of precise and comprehensive diversity data for flora research. Due to variations in the description of flora across different countries in Northeast Asia, it is essential to update our understanding of the region’s overall flora using the latest high-quality diversity data. This study employed the most recently published authoritative data from various countries to conduct a statistical analysis of 225 families, 1782 genera, and 10,514 native vascular species and infraspecific taxa in Northeast Asia. Furthermore, species distribution data were incorporated to delineate three gradients in the overall distribution pattern of plant diversity in Northeast Asia. Specifically, Japan (excluding Hokkaido) emerged as the most prolific hotspot for species, followed by the Korean Peninsula and the coastal areas of Northeast China as the second richest hotspots. Conversely, Hokkaido, inland Northeast China, and Mongolia constituted species barren spots. The formation of the diversity gradients is primarily attributed to the effects of latitude and continental gradients, with altitude and topographic factors within the gradients modulating the distribution of species.

The heterogeneity of triple negative breast cancer (TNBC) results in the worst prognosis among breast cancer types, making its treatment strategy very challenging. A recent study showed that oleanolic acid (OA) has a radiosensitizing effect on tumor cells, but it does not show a good clinical effect when used alone in radiotherapy. The cytotoxicity of radiotherapy can be enhanced by modulating DNA repair, so new treatment options are being investigated to inhibit DNA repair pathways and sensitize tumors to radiation. Radiation induces DNA double-strand breaks (DSBs), and inhibition of Poly (ADP-Ribose) polymerase (PARP) can prevent the repair of these lesions. Hence, we evaluated the radiosensitization and the underlying mechanism of combination treatment with OA and olaparib in TNBC. Meanwhile, tumor hypoxia was monitored with 18F-Fluoroerythronitroimidazole (FETNIM) positron emission tomography/computed tomography (PET/CT) during radiosensitization therapy. Here, we found that OA and olaparib in combination with radiotherapy significantly inhibited cell proliferation compared with other groups. The results were observed using colony formation assays [sensitization enhancement ratios (SER) 1.16–1.65]. In vivo, tumor growth was significantly delayed in transplanted tumors receiving irradiation (IR) with OA and olaparib. 18F-FETNIM PET/CT can be utilized for tumor hypoxia monitoring and radiosensitization response evaluation. In conclusion, these results suggest that the combination of OA and olaparib with IR enhances the inhibition of MDA-MB-231 in cell culture and in mice, providing a potentially novel combination for the effective treatment of TNBC patients.

In this paper, a hot processing map that takes into the strengthening effect into account is optimized for the Al–10.0Zn–3.0Mg–2.8Cu alloy, mainly considering the crushing and dissolving behavior of the insoluble phase. The hot deformation experiments were performed by compression testing with strain rates ranging from 0.001 to 1 s−1 and the temperature ranging from 380 to 460 °C. The hot processing map was established at the strain of 0.9. It exhibits that the appropriate hot processing region is located at the temperature from 431 to 456 °C and its strain rate is within 0.004–0.108 s−1. The recrystallization mechanisms and insoluble phase evolution were demonstrated using the real-time EBSD-EDS detection technology for this alloy. It is verified that the work hardening can also be consumed by the coarse insoluble phase refinement with the strain rate increasing from 0.001 to 0.1 s−1, besides the traditional recovery and recrystallization, but the effect of the insoluble phase crushing was weakened when strain rate increased over 0.1 s−1. Better refinement of the insoluble phase was around strain rate in 0.1 s−1, which exhibits adequate dissolving during the solid solution treatment, leading to excellent aging strengthen effects. Finally, the hot processing region was further optimized, so that the strain rate approaches 0.1 s−1 instead of 0.004–0.108 s−1. This will provide a theoretical support for the subsequent deformation of the Al–10.0Zn–3.0Mg–2.8Cu alloy and its’ engineering application in aerospace, defense and military fields.

Rosa glomerata is a diffuse shrub belonging to Rosa sect. Synstylae. It is endemic to Southwest China and of high ornamental and economic value. However, its systematic position remains unclear. Here, the complete chloroplast genome of R. glomerata was assembled using high-throughput sequencing data. The cp genome is 157,064 bp in length with a large single-copy region (LSC) of 86,216 bp, a small single-copy region (SSC) of 18,752 bp, and a pair of inverted repeats (IRs) of 26,048 bp. The overall GC content is 37.2%. A total of 137 genes were annotated, including 90 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis revealed that R. glomerata is closely related to R. praelucens of R. sect. Microphyllae rather than species of R. sect. Synstylae.

Tumorigenesis is associated with metabolic abnormalities and genomic instability. Microsatellite mutations, including microsatellite instability (MSI) and loss of heterozygosity (LOH), are associated with the functional impairment of some tumor-related genes. To investigate the role of MSI and LOH in sporadic breast tumors in canines, 22 tumors DNA samples and their adjacent normal tissues were evaluated using polyacrylamide gel electrophoresis and silver staining for 58 microsatellites. Quantitative real-time polymerase chain reaction, promoter methylation analysis and immunohistochemical staining were used to quantify gene expression. The results revealed that a total of 14 tumors (6 benign tumors and 8 breast cancers) exhibited instability as MSI-Low tumors. Most of the microsatellite loci possessed a single occurrence of mutations. The maximum number of MSI mutations on loci was observed in tumors with a lower degree of differentiation. Among the unstable markers, FH2060 (4/22), ABCC9tetra (4/22) and SCN11A (6/22) were high-frequency mutation sites, whereas FH2060 was a high-frequency LOH site (4/22). The ABCC9tetra locus was mutated only in cancerous tissue, although it was excluded by transcription. The corresponding genes and proteins were significantly downregulated in malignant tissues, particularly in tumors with MSI. Furthermore, the promoter methylation results of the adenosine triphosphate binding cassette subfamily C member 9 (ABCC9) showed that there was a high level of methylation in breast tissues, but only one case showed a significant elevation compared with the control. In conclusion, MSI-Low or MSI-Stable is characteristic of most sporadic mammary tumors. Genes associated with tumorigenesis are more likely to develop MSI. ABCC9 protein and transcription abnormalities may be associated with ABCC9tetra instability.

Background: The prognosis of and occurrence of complications in patients with different clinical features of cirrhosis differ, and cirrhosis with different etiologies has varying clinical characteristics. The aim of this study was to describe the liver function markers, hepatic complications, and psychological features differentiating patients with hepatitis B virus (HBV) infection-related and alcohol-related cirrhosis. Materials and Methods: This was a retrospective and observational study that analyzed the medical data of inpatients with alcohol-related or HBV infection-related cirrhosis from May 2014 to May 2020. Markers of liver function, portal hypertension, and psychological symptoms were compared between the two groups. Results: Patients with alcohol-related cirrhosis showed higher Self-Rating Anxiety Scale scores and prevalence of hypoproteinemia, fatty liver, and depression than those with HBV infection-related cirrhosis (all P < 0.05). After adjustment for potential confounders, patients with alcohol-related cirrhosis also showed higher risks of increased total cholesterol (odds ratio [OR] =2.671, 95% confidence interval [CI]: 1.160–6.151, P = 0.021), increased high-density lipoprotein-cholesterol (OR = 2.714, 95% CI: 1.009–7.299, P = 0.048), and fatty liver (OR = 2.713, 95% CI: 1.002–7.215, P = 0.048); however, splenomegaly and splenectomy were significantly associated with HBV infection-related cirrhosis (OR = 2.320, 95% CI: 1.066–5.050, P = 0.034). Conclusion: Patients with alcohol-related cirrhosis were more likely to develop hyperlipidemia, fatty liver, and psychological symptoms, whereas those with HBV-related cirrhosis had a higher risk of splenomegaly.

Abstract Objective To discuss the diagnostic value of multislice spiral tomography (CT) combined with CT angiography (CTA) technology in intra-abdominal undescended testis secondary seminoma cases. Methods We retrospectively analyzed the CT and CTA imaging features of CT and CTA findings of nine patients with an intra-abdominal undescended testis secondary seminoma. Results The tumors in all nine patients were mainly solid, and the average CT value was 38.4 ± 3.4 HU. Low-density areas of various sizes were visible in the tumors, and calcifications were detected in two patients. The tumors in eight patients had a complete capsule, which pressed on the surrounding structures. In one patient, the tumor had an incomplete capsule, which invaded the surrounding structures. Some of the solid tumors showed progressive and slight enhancement on the CT-enhanced scans. The values in the arterial phase, venous phase, and delayed phase were 46.3 ± 5.1 (40–55 HU), 57.3 ± 7.3HU (48–68 HU), and 65.1 ± 7.2HU (56–77 HU), respectively, with an average increase rate of 27.0 ± 7.2 HU. No enhancement was found in low-density areas on the CTA scans, and the supply arteries of the tumors in the nine patients all originated from the abdominal aortic wall 2–3 cm below the renal ostia. These arteries became thickened and tortuous when near the tumors, and there were no branching vessels. In eight patients, the supply arteries of the tumors originated from the posterior tumor and ended inside the tumor, and they originated from anterior of the tumor in one patient. Testicular venous drainage was detected in three patients, and lymph node metastasis in the abdominal aorta detected in two cases. Conclusion An intra-abdominal undescended testis secondary seminoma exhibits a characteristic appearance on CT. CTA shows a three-dimensional testicular vascular pedicle sign of a seminoma. A combination of CT and CTA can improve the diagnostic accuracy of an intra-abdominal undescended testis secondary seminoma.

Abstract Background Baicalin, which is isolated from Radix Scutellariae, possesses strong biological activities including an anti-inflammation property. Recent studies have shown that the anti-inflammatory effect of baicalin is linked to toll-like receptor 4 (TLR4), which participates in pathological changes of central nervous system diseases such as depression. In this study, we explored whether baicalin could produce antidepressant effects via regulation of TLR4 signaling in mice and attempted to elucidate the underlying mechanisms. Methods A chronic unpredictable mild stress (CUMS) mice model was performed to explore whether baicalin could produce antidepressant effects via the inhibition of neuroinflammation. To clarify the role of TLR4 in the anti-neuroinflammatory efficacy of baicalin, a lipopolysaccharide (LPS) was employed in mice to specially activate TLR4 and the behavioral changes were determined. Furthermore, we used LY294002 to examine the molecular mechanisms of baicalin in regulating the expression of TLR4 in vivo and in vitro using western blot, ELISA kits, and immunostaining. In the in vitro tests, the BV2 microglia cell lines and primary microglia cultures were pretreated with baicalin and LY292002 for 1 h and then stimulated 24 h with LPS. The primary microglial cells were transfected with the forkhead transcription factor forkhead box protein O 1 (FoxO1)-specific siRNA for 5 h and then co-stimulated with baicalin and LPS to investigate whether FoxO1 participated in the effect of baicalin on TLR4 expression. Results The administration of baicalin (especially 60 mg/kg) dramatically ameliorated CUMS-induced depressive-like symptoms; substantially decreased the levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) in the hippocampus; and significantly decreased the expression of TLR4. The activation of TLR4 by the LPS triggered neuroinflammation and evoked depressive-like behaviors in mice, which were also alleviated by the treatment with baicalin (60 mg/kg). Furthermore, the application of baicalin significantly increased the phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and FoxO1. The application of baicalin also promoted FoxO1 nuclear exclusion and contributed to the inhibition of the FoxO1 transactivation potential, which led to the downregulation of the expression of TLR4 in CUMS mice or LPS-treated BV2 cells and primary microglia cells. However, prophylactic treatment of LY294002 abolished the above effects of baicalin. In addition, we found that FoxO1 played a vital role in baicalin by regulating the TLR4 and TLR4-mediating neuroinflammation triggered by the LPS via knocking down the expression of FoxO1 in the primary microglia. Conclusion Collectively, these results demonstrate that baicalin ameliorated neuroinflammation-induced depressive-like behaviors through the inhibition of TLR4 expression via the PI3K/AKT/FoxO1 pathway.

Objective: To predict B cell and T cell epitopes of 22-kDa, 47-kDa, 56-kDa and 58-kDa proteins. Methods: The sequences of 22-kDa, 47-kDa, 56-kDa and 58-kDa proteins which were derived from Orientia tsutsugamushi were analyzed by SOPMA, DNAstar, Bcepred, ABCpred, NetMHC, NetMHC II and IEDB. The 58-kDa tertiary structure model was built by MODELLER9.17. Results: The 22-kDa B-cell epitopes were located at positions 194-200, 20-26 and 143-154, whereas the T-cell epitopes were located at positions 154-174, 95-107, 17-25 and 57-65. The 47-kDa protein B-cell epitopes were at positions 413-434, 150-161 and 283-322, whereas the T-cell epitopes were located at positions 129-147, 259-267, 412-420 and 80-88. The 56-kDa protein B-cell epitopes were at positions 167-173, 410-419 and 101-108, whereas the T-cell epitopes were located at positions 88-104, 429-439, 232-240 and 194-202. The 58-kDa protein B-cell epitopes were at positions 312-317, 540-548 and 35-55, whereas the T-cell epitopes were located at positions 415-434, 66-84 and 214-230. Conclusions: We identified candidate epitopes of 22-kDa, 47-kDa, 56-kDa and 58- kDa proteins from Orientia tsutsugamushi. In the case of 58-kDa, the dominant antigen is displayed on tertiary structure by homology modeling. Our findings will help target additional recombinant antigens with strong specificity, high sensitivity, and stable expression and will aid in their isolation and purification.

Subsurface wastewater infiltration systems (SWIS) are one of the important sources of nitrous oxide (N2O) production; understanding the biological processes and contributions of N2O will help control the amount of N2O produced. To quantitatively reveal the contribution of nitrification and denitrifiaction processes, 8 g potassium nitrate with 99.99 atom % 15N (i.e. 15N accounts for 99.99% of the total N) was dissolved in the influent (concentration: 3.3 g/L). Results showed that nitrification released more N2O within 0–12 h, accounting for 79.6 ± 2.4%. The denitrification process accounted for 88.5 ± 1.3% for N2O generation after the 12th hour. Thus, in order to effectively control the release of N2O, the denitrification process should be given more attention. The maximum release rate of N2O was 8.45 ± 0.8 mg/m2·h, which occurred near the end of the first wetting-drying cycle. Since then, peaks appeared periodically, mostly in the “rest” periods.

The concentration of total nitrogen (TN) is reported to vary between 20 and 35 mg/L in domestic wastewater. In raw wastewater, ammonia nitrogen (NH4+-N) is the main nitrogen form, accounting for 70%–82% of the TN concentration. Organic nitrogen, nitrite nitrogen (NO2−-N), and nitrate nitrogen (NO3−-N) are present as well. For years, due to the lack of regulatory limits on nitrogen concentration in surface waters, nitrogen from secondary effluent has posed a significant threat to the health of aquatic ecosystems. Researchers have made substantial efforts to reduce the nitrogen concentration in secondary effluent. As a kind of advanced wastewater treatment technology, the subsurface infiltration (SI) system has been widely used, owing to its advantages, which include low operation cost, easy maintenance, and low energy consumption. This review discusses the fate of various forms of nitrogen in SI treatment, including organic nitrogen, NH4+-N, NO2−-N, and NO3−-N. Major biological processes involved in nitrogen removal and the main factors influencing its transformation are suggested. Finally, it is shown that ammonification followed by nitrification-denitrification plays a major role in nitrogen removal. Further research needs to focus on the emission characteristics of gaseous nitrogen (generated from the nitrification, denitrification, and completely autotrophic nitrogen-removal over nitrite (CANON) processes) with respect to their greenhouse effects.

To understand the genetic background of Rosa filipes, its complete chloroplast genome was determined in this study. The chloroplast genome of R. filipes is 156,624 bp in length with a large single-copy region (LSC) of 85,754 bp, a small single-copy region (SSC) of 18,784 bp, and a pair inverted repeats (IRs) of 26,043 bp. The GC content is 37.2%. A total of 137 genes were identified, including 90 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Phylogenetic analysis indicated that R. filipes is closely related to R. chinensis var. spontanea.

Tumor-initiating cells (TIC) are dynamic cancer cell subsets that display enhanced tumor functions and resilience to treatment but the mechanism of TIC induction or maintenance in lung cancer is not fully understood. In this study, we show the calcium pathway transcription factor NFATc2 is a novel regulator of lung TIC phenotypes, including tumorspheres, cell motility, tumorigenesis, as well as in vitro and in vivo responses to chemotherapy and targeted therapy. In human lung cancers, high NFATc2 expression predicted poor tumor differentiation, adverse recurrence-free and cancer-specific overall survivals. Mechanistic investigations identified NFATc2 response elements in the 3’ enhancer region of SOX2, and NFATc2/SOX2 coupling upregulates ALDH1A1 by binding to its 5’ enhancer. Through this axis, oxidative stress induced by cancer drug treatment is attenuated, leading to increased resistance in a mutation-independent manner. Targeting this axis provides a novel approach for the long-term treatment of lung cancer through TIC elimination.

Background and foreground modeling is a typical method in the application of computer vision. The current general “low-rank + sparse” model decomposes the frames from the video sequences into low-rank background and sparse foreground. But the sparse assumption in such a model may not conform with the reality, and the model cannot directly reflect the correlation between the background and foreground either. Thus, we present a novel model to solve this problem by decomposing the arranged data matrix D into low-rank background L and moving foreground M. Here, we only need to give the priori assumption of the background to be low-rank and let the foreground be separated from the background as much as possible. Based on this division, we use a pair of dual norms, nuclear norm and spectral norm, to regularize the foreground and background, respectively. Furthermore, we use a reweighted function instead of the normal norm so as to get a better and faster approximation model. Detailed explanation based on linear algebra about our two models will be presented in this paper. By the observation of the experimental results, we can see that our model can get better background modeling, and even simplified versions of our algorithms perform better than mainstream techniques IALM and GoDec.

RNA biogenesis, including biosynthesis and maturation of rRNA, tRNA and mRNA, is a fundamental process that is critical for cell growth, division and differentiation. Previous studies showed that mutations in components involved in RNA biogenesis resulted in abnormalities in gametophyte and leaf development in Arabidopsis. In eukaryotes, RNases P/MRP (RNase mitochondrial RNA processing) are important ribonucleases that are responsible for processing of tRNA, and transcription of small non-coding RNAs. Here we report that Gametophyte Defective 1 (GAF1), a gene encoding a predicted protein subunit of RNases P/MRP, AtRPP30, plays a role in female gametophyte development and male competence. Embryo sacs were arrested at stages ranging from FG1 to FG7 in gaf1 mutant, suggesting that the progression of the gametophytic division during female gametogenesis was impaired in gaf1 mutant. In contrast, pollen development was not affected in gaf1. However, the fitness of the mutant pollen tube was weaker than that of the wild-type, leading to reduced transmission through the male gametes. GAF1 is featured as a typical RPP30 domain protein and interacts physically with AtPOP5, a homologue of RNases P/MRP subunit POP5 of yeast. Together, our data suggest that components of the RNases P/MRP family, such as RPP30, play important roles in gametophyte development and function in plants.

BACKGROUND: While prions play a central role in the pathogenesis of transmissible spongiform encephalopathies, the biology of these proteins and the pathophysiology of these diseases remain largely unknown. Since no case of bovine spongiform encephalopathy (BSE) has ever been reported in buffalo despite their phylogenetic proximity to cattle, genetic differences may be driving the different susceptibilities of these two species to BSE. We thus hypothesized that differences in expression of the most recently identified member of the prion family or Shadoo (SPRN) gene may relate to these species-specific differences. PRINCIPAL FINDINGS: We first analyzed and compared the polymorphisms of the SPRN gene (~4.4 kb), including the putative promoter, coding and 3' regions, and further verified the entire ORF and putative promoter. This yielded a total of 117 fixed differences, remarkably: 1) a 12-bp insertion/deletion polymorphism in the hydrophobic domain of the cattle but not buffalo gene, introducing a four amino acid expansion/contraction in a series of 5 tandem Ala/Gly-containing repeats; 2) two fixed missense mutations (102Ser→Gly and 119Thr→Ala), and three missense mutations (92Pro>Thr/Met, 122Thr>Ile and 139Arg>Trp) in the coding region presenting different (P

Premise of the study: Microsatellite loci were developed for Prunus sibirica to investigate genetic diversity, population genetic structure, and marker-assisted selection of late-blooming cultivars in the breeding of P. sibirica. Methods and Results: Using a magnetic bead enrichment strategy, 19 primer pairs were developed and characterized across 40 individuals from three P. sibirica wild populations and six individuals of P. armeniaca. The number of alleles per locus varied from three to 11 and the observed and expected heterozygosities ranged from 0.063 to 0.917 and 0.295 to 0.876, respectively, in the three P. sibirica wild populations. All primer pairs could be successfully amplified in six individuals of P. armeniaca. Conclusions: These microsatellite primer pairs should be useful for population genetics, germplasm identification, and marker-assisted selection in the breeding of P. sibirica and related species.