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Non-invasive determination of amyloid-β peptide (Aβ) and tau deposition are important for early diagnosis and therapeutic intervention for Alzheimer's disease (AD) and non-AD tauopathies. In the present study, we investigated the capacity of a novel radioiodinated compound AD-DRK ( 123/125 I-AD-DRK) with 50% inhibitory concentrations of 11 nM and 2 nM for Aβ and tau aggregates, respectively, as a single photon emission computed tomography (SPECT) ligand in living brains. In vitro and ex vivo autoradiography with 125 I-AD-DRK was performed in postmortem human and two transgenic (Tg) mice lines with either fibrillar Aβ or tau accumulation, APP23 and rTg4510 mice. SPECT imaging of 123 I-AD-DRK was performed in APP23 mice to investigate the ability of AD-DRK to visualize fibrillar protein deposition in the living brain. In-vitro autoradiogram of 125 I-AD-DRK showed high specific radioactivity accumulation in the temporal cortex and hippocampus of AD patients and the motor cortex of progressive supranuclear palsy (PSP) patients enriched by Aβ and/or tau aggregates. Ex-vivo autoradiographic images also demonstrated a significant increase in 125 I-AD-DRK binding in the forebrain of both APP23 and rTg450 mice compared to their corresponding non-Tg littermates. SPECT imaging successfully captured Aβ deposition in the living brain of aged APP23 mice. The present study developed a novel high-contrast SPECT agent for assisting the diagnosis of AD and non-AD tauopathies, likely benefiting from its affinity for both fibrillar Aβ and tau., Competing Interests: Declaration of competing interest Shanghai Fuji Medical Technology Co. LTD hold patents on compounds related to the present report (JP6831802/KR10–2,428,569). The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Multiple linked single nucleotide polymorphisms (SNPs) have shown potential in personal identification and mixture detection. However, the limited number of marker and sequencing errors have obstructed accurate DNA typing., Methods: To develop more candidate loci, the diversity value (D-value) was introduced as a new parameter for screening the novel polymorphic multiple linked-SNP markers, referred to as multi-SNP. In this study, a "FD Multi-SNP Mixture Kit" comprising 567 multi-SNPs was developed for mixture detection. Additionally, a new computational error correction method was applied as a quality control approach for sequencing data., Results: The results demonstrated higher typing success rates than the conventional CE typing method. For single-source DNA, approximately 70-80 loci were detected with a DNA input of 0.009765625 ng. More than 65% of the minor alleles were distinguishable at 1 ng DNA with a frequency of 0.5% in 2- to 4-person mixtures., Conclusion: This study offers a polymorphic and high-resolution detection method for DNA genotyping and complex mixture detection, providing an alternative strategy for addressing challenging mixed DNA traces., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Li, Zhou, Li, Yuan, Peng, Li and Zhang.)

Objective: To investigate the value of intraoperative assessment of spread through air spaces (STAS) on frozen sections (FS) in peripheral small-sized lung adenocarcinoma., Background: Surgical decision-making based on FS diagnosis of STAS may be useful to prevent local control failure after sublobar resection., Methods: We conducted a multicenter prospective observational study of consecutive patients with cT1N0M0 invasive lung adenocarcinoma to evaluate the accuracy of FS for the intraoperative detection of STAS. The final pathology (FP) diagnosis of STAS was based on corresponding permanent paraffin sections., Results: This study included 878 patients with cT1N0M0 invasive lung adenocarcinoma. A total of 833 cases (95%) were assessable for STAS on FS. 26.4% of the cases evaluated positive for STAS on FP, whereas 18.2% on FS. The accuracy, sensitivity, and specificity of FS diagnosis of STAS were 85.1%, 56.4%, and 95.4%, respectively, with moderate agreement (κ=0.575). Inter-observer agreement was substantial (κ=0.756) among the three pathologists. Subgroup analysis based on tumor size or consolidation-to-tumor ratio all showed moderate agreement for concordance. After rigorous reassessment of false-positive cases, the presence of artifacts may be the main cause of interpretation errors. Additionally, true positive cases showed more high-grade histological patterns and more advanced p-TNM stages than false negative cases., Conclusions: This is the largest prospective observational study to evaluate STAS on FS in patients with cT1N0M0 invasive lung adenocarcinoma. FS is highly specific with moderate agreement, but is not sensitive for STAS detection. While appropriately reporting STAS on FS may provide surgeons with valuable information for intraoperative decision-making, better approaches are needed., Competing Interests: Disclosure: The authors declare no relevant conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: This study aims to assess the diagnostic accuracy of the intraoperative frozen section (FS) in determining the pathological subtypes among patients diagnosed with cT1N0M0 invasive lung adenocarcinoma., Materials and Methods: This was a prospective, multicenter (seven centers in China) clinical trial of Eastern Cooperative Thoracic Oncology Projects (ECTOP-1015). Patients with cT1N0M0 invasive lung adenocarcinoma were enrolled in the study. Pathological images obtained from FS and final pathology (FP) were reviewed by at least two pathologists. The primary endpoint was the concordance between FS and FP diagnoses. The interobserver agreement for identifying pathological subtypes on FS was evaluated among three pathologists., Results: A total of 935 patients were enrolled. The best sensitivity of diagnosing the predominant subtype was 78.2% in the evaluation of the acinar pattern. The presence of an acinar pattern diagnosed by FS was an independent factor for the concordance between FS and FP ( P =0.007, 95% confidence interval: 2.332-4.736). Patients with tumor size >2 cm measured by pathology showed a better concordance rate for the predominant subtype (81.6% vs. 74.6%, P =0.023). The presence of radiological ground glass opacity component did not affect the diagnosis accuracy of FS for the predominant subtype (concordance rate: 76.4% vs. 75.2%, P =0.687). Patients with ground glass opacity component showed better accuracy of the identification in the presence of lepidic pattern-predominant adenocarcinoma (82.1% vs. 71.0%, P =0.026). Substantial agreement between the FS diagnosis from three pathologists for the predominant pathological pattern was revealed with κ=0.846., Conclusions: This is the largest prospective trial evaluating FS diagnosing pathological subtype in cT1N0M0 invasive lung adenocarcinoma. A favorable concordance in the assessment of the pathological subtypes between FS and FP was observed, indicating the feasibility of utilizing accurate intraoperative pathological diagnoses from FS in guiding surgical strategies. A combination of radiology could improve the precision of FS., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aims: Ubiquitin specific peptidase 5 (USP5), a member of deubiquitinating enzymes, has garnered significant attention for its crucial role in cancer progression. This study aims to explore the role of USP5 and its potential molecular mechanisms in cholangiocarcinoma (CCA)., Main Methods: To explore the effect of USP5 on CCA, gain-of-function and loss-of-function assays were conducted in human CCA cell lines RBE and HCCC9810. The CCK8, colony-forming assay, EDU, flow cytometry, transwell assay and xenografts were used to assess cell proliferation, migration and tumorigenesis. Western blot and immunohistochemistry were performed to measure the expression of related proteins. Immunoprecipitation and immunofluorescence were applied to identify the interaction between USP5 and Y box-binding protein 1 (YBX1). Ubiquitination assays and cycloheximide chase assays were carried out to confirm the effect of USP5 on YBX1., Key Findings: We found USP5 is highly expressed in CCA tissues, and upregulated USP5 is required for the cancer progression. Knockdown of USP5 inhibited cell proliferation, migration and epithelial-mesenchymal transition (EMT) in vitro, along with suppressed xenograft tumor growth and metastasis in vivo. Mechanistically, USP5 could interact with YBX1 and stabilize YBX1 by deubiquitination in CCA cells. Additionally, silencing of USP5 hindered the phosphorylation of YBX1 at serine 102 and its subsequent translocation to the nucleus. Notably, the effect induced by USP5 overexpression in CCA cells was reversed by YBX1 silencing., Significance: Our findings reveal that USP5 is required for cell proliferation, migration and EMT in CCA by stabilizing YBX1, suggesting USP5-YBX1 axis as a promising therapeutic target for CCA., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Protocatechuic acid (PCA) and protocatechuic aldehyde (PAL) are important phenolic compounds in plants. We here investigated their possible beneficial effect against fungal infection and the underlying mechanism. The model animal of Caenorhabditis elegans was used as host, and Candida albicans was used as fungal pathogen. The nematodes were first infected with C. albicans , and the PCA and PAL treatment were then performed. Post-treatment with 10-100 μM PCA and PAL suppressed toxicity of C . albicans infection in reducing lifespan. Accompanied with this beneficial effect, treatment with 10-100 μM PCA and PAL inhibited C. albicans accumulation in intestinal lumen. In addition, treatment with 10-100 μM PCA and PAL suppressed the increase in expressions of antimicrobial genes caused by C. albicans infection. The beneficial effect of PCA and PAL against C. albicans infection depended on p38 MAPK and insulin signals. Moreover, although treatment with 10-100 μM PCA and PAL could not exhibit noticeable antifungal activity, PCA and PAL treatment obviously suppressed biofilm formation, inhibited hyphal growth, and reduced expressions of virulence genes ( ALS3 , CaVps34 , Vma7 , Vac1 , and/or HWP1 ) related to biofilm formation and hyphal growth in C. albicans . Therefore, our data demonstrated the potential of PCA and PAL post-treatment against fungal infection and fungal virulence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yuan, Wang, Zhang and Wang.)

Biological traces discovered at crime scenes hold significant significance in forensic investigations. In cases involving mixed body fluid stains, the evidentiary value of DNA profiles depends on the type of body fluid from which the DNA was obtained. Recently, coding region polymorphism analysis has proved to be a promising method for directly linking specific body fluids to their respective DNA contributors in mixtures, which may help to avoid "association fallacy" between separate DNA and RNA evidence. In this study, we present an update on previously reported coding region Single Nucleotide Polymorphisms (cSNPs) by exploring the potential application of coding region Insertion/Deletion polymorphisms (cInDels). Nine promising cInDels, selected from 70 mRNA markers based on stringent screening criteria, were integrated into an existing mRNA profiling assay. Subsequently, the body fluid specificity of our cInDel assay and the genotyping consistency between complementary DNA (cDNA) and genomic DNA (gDNA) were examined. Our study demonstrates that cInDels can function as important multifunctional genetic markers, as they provide not only the ability to confirm the presence of forensically relevant body fluids, but also the ability to associate/dissociate specific body fluids with particular donors., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest. Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To study the clinical application value of contrast-enhanced ultrasound (CEUS) in diagnosing renal space-occupying lesions., Methods: Sixty-seven patients with renal space-occupying lesions detected by routine ultrasound examination received the contrast-enhanced ultrasound examination. When observing the perfusion mode of the mass, we analyzed the perfusion characteristics of contrast-enhanced ultrasound and compared them with the surgical pathological results., Results: Sixty-seven lesions, which were identified in 67 patients with renal space-occupying lesions, included 55 renal malignant tumors and 12 benign ones. The sensitivity of qualitative diagnosis by CEUS imaging was 96.4%, the specificity was 66.7%, and the accuracy was 91.0%., Conclusion: The real-time blood supply of renal space-occupying lesions helps judge their nature according to the enhancement mode. It has high clinical application value in diagnosing benign and malignant lesions., Competing Interests: No potential conflict of interest was reported by the authors., (© 2023 Liu et al.)

Background: The exertion of motor function depends on various tissues, such as bones and muscles. miR-196 has been widely studied in cancer and other fields, but its effect on bone and skeletal muscle is rarely reported. In order to explore the role of miR-196 family in bone and skeletal muscle, we used the previously successfully constructed miR-196a-1 and miR-196b gene knockout zebrafish animal models for research., Methods: The behavioral trajectories of zebrafish from 4 days post-fertilization (dpf) to 7 dpf were detected to analyze the effect of miR-196a-1 and miR-196b on motor ability. Hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) were used to detect the dorsal muscle tissue of zebrafish. The bone tissue of zebrafish was detected by microcomputed tomography (micro-CT). Real-time PCR was used to detect the expression levels of related genes, including vcp, dpm1, acta1b, mylpfb, col1a1a, bmp8a, gdf6a, and fgfr3., Results: The behavioral test showed that the total behavioral trajectory, movement time, and movement speed of zebrafish larvae were decreased in the miR-196a-1 and miR-196b gene knockout lines. Muscle tissue analysis showed that the structure of muscle fibers in the zebrafish lacking miR-196a-1 and miR-196b was abnormal and was characterized by vacuolar degeneration of muscle fibers, intranuclear migration, melanin deposition, and inflammatory cell infiltration. Bone CT examination revealed decreased bone mineral density and trabecular bone number. The real-time PCR results showed that the expression levels of vcp, dpm1, gdf6a, fgfr3, and col1a1a were decreased in the miR-196b gene knockout group. The expression levels of dpm1, acta1b, mylpfb, gdf6a, and col1a1a were decreased, and the expression level of fgfr3 was increased in the miR-196b gene knockout group compared with the wild-type group., Conclusions: miR-196a-1 and miR-196b play an important role in muscle fiber structure, bone mineral density, and bone trabecular quantity by affecting the expression of vcp, dpm1, acta1b, mylpfb, gdf6a, fgfr3, and col1a1a and then affect the function of the motor system.

The wide dynamic range of serum proteome restrained discovery of clinically interested proteins in large cohort studies. Herein, we presented a high-sensitivity, high-throughput, and precise pan-targeted serum proteomic strategy for highly efficient cancer serum proteomic research and biomarker discovery. We constructed a resource of over 2000 cancer-secreted proteins, and the standard MS assays and spectra of at least one synthetic unique peptide per protein were acquired and documented (Cancer Serum Atlas, www.cancerserumatlas.com). Then, the standard peptide-anchored parallel reaction monitoring (SPA-PRM) method was developed with support of the Cancer Serum Atlas, achieving precise quantification of cancer-secreted proteins with high throughput and sensitivity. We directly quantified 325 cancer-related serum proteins in 288 serums of four cancer types (liver, stomach, lung, breast) and controls with the pan-targeted strategy and discovered considerable potential biomarker benefits for early detection of cancer. Finally, a proteomic-based multicancer detection model was built, demonstrating high sensitivity (87.2%) and specificity (100%), with 73.8% localization accuracy for an independent test set. In conclusion, the Cancer Serum Atlas provides a wide range of potential biomarkers that serve as targets and standard assays for systematic and highly efficient serological studies of cancer. The Cancer Serum Atlas-supported pan-targeted proteomic strategy enables highly efficient biomarker discovery and multicancer detection and thus can be a powerful tool for liquid biopsy.

Completely loss of granular structural stability and reliable start-up of aerobic granular sludge (AGS) system are considered as the biggest challenges for its engineering application under seasonal temperature variation, especially extremely low temperatures. In this study, two identical sequencing batch reactors (SBR) were successfully start-up at 10 °C (R1) and 25 °C (R2), respectively, and then operated under a strategy of stepwise change of temperatures to investigate the stability of the granular sludge by examining its microbial characteristics, bis (3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP), extracellular polymeric substance (EPS) and sludge physiochemical properties. The results showed that AGS formed under the low temperature preferentially secrete EPS and c-di-GMP for stable granulation and improvement of its resistance to temperature changes. Meanwhile, R1 successfully obtained aerobic granulation with high biomass concentration and superior settleability, as well as high pollutant removal performance. In comparison, R2 took a longer time for granulation and was subjected to serious disintegration of AGS. The matrix structure partially formed by filamentous bacteria during the start-up stage in R1 was one of major reasons for its own superiority beyond R2 in granulation. Slow-growing organisms such as autotrophic nitrifying and Anammox bacteria, phosphorus accumulation organisms, EPS-producing genera, and c-di-GMP pathway-dependent genera, were exclusively enriched in the R1 and resulted in higher pollutants removal efficiencies and stable structure, whereas Sphaerotilus dominated in R2 that related closely with its unstable performance. Therefore, the strategy based on the stepwise change of temperatures from extremely low temperatures may be one feasible way for the sustainable application of AGS system, which is of significance to address the challenging problems of AGS applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Y-chromosome single nucleotide polymorphism (Y-SNP) shows great variation in geographical distribution and population heterogeneity and can be used to map population genetics around the world. Massive parallel sequencing (MPS) methodology enables high-resolution Y-SNP haplogrouping for a certain male and is widely used in forensic genetics and evolutionary studies. In this present study, we used MPS to develop a customized 381 Y-SNP panel (SifaMPS 381 Y-SNP panel) to investigate the basic structure and subbranches of the haplogroup tree of the Chinese populations. The SifaMPS 381 Y-SNP panel covers all the Y-SNPs from our previously designed 183 Y-SNP panel and additional SNPs under the predominant haplogroups in the Chinese populations based on certain criteria. We also evaluated the sequencing matrix, concordance, sensitivity, repeatability of this panel and the ability to analyze mixed and case-type samples based on the Illumina MiSeq System. The results demonstrated that the novel MPS Y-SNP panel possessed good sequencing performance and generated accurate Y-SNP genotyping results. Although the recommended DNA input was greater than 1.25 ng, we observed that a lower DNA amount could still be used to analyze haplogroups correctly. In addition, this panel could handle mixed samples and common case-type samples and had higher resolution among Chinese Han males than previously reported. In conclusion, the SifaMPS 381 Y-SNP panel showed an overall good performance and offers a better choice for Y-SNP haplogrouping of the Chinese population, thereby facilitating paternal lineage classification, familial searching and other forensic applications., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Tightly bound extracellular polymeric substances (TB-EPS) and loosely bound extracellular polymeric substances (LB-EPS) affect the flocculability and settleability of sludge and the transfer of oxygen, which are highly related to aeration. In this study, we systemically evaluated the expanded unified model-TL2.1 for its long-term simulation of TB-EPS and LB-EPS. Two different aeration conditions and three different influent carbon sources were used to evaluate the model, and the simulation results fit well with the experimental data. TB-EPS and LB-EPS production increased with aeration intensity. The influence of aeration parameters on TB-EPS and LB-EPS production in a short-term batch system and long-term sequencing batch reactor (SBR) system was compared. The aeration parameters included the total transfer coefficient (k L a) and the concentration of dissolved oxygen at the interface (C S ). To ensure a high removal rate of substrates and ammonia nitrogen and achieve a stable active biomass concentration, the following aeration parameters can be adopted to reduce energy wastage during aeration: when C S is 2 mg/L, k L a can be set above 30 h -1 and below 50 h -1 ; when k L a is 50 h -1 , C S can be set above 1 mg/L and below 1.5 mg/L. This study systematically revealed the influence of aeration on TB-EPS and LB-EPS formation in an SBR system through a mathematical model, and it provides a theoretical basis for better understanding aeration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Imatinib, an inhibitor of tyrosine kinase, shows remarkable efficacy in chronic myeloid leukaemia (CML). Autophagy protects tumour cells against chemotherapeutic stimulation and contributes to imatinib resistance in CML. Kinesin family member 23 (KIF23) is involved in cytokinesis and associated with autophagy. The role of KIF23 in autophagy-induced imatinib resistance in CML was investigated. First, to induce drug resistance, CML cells were exposed to increasing concentrations of imatinib. The concentration of imatinib resistance in CML cells was screened through upregulation of 50% inhibitory concentration (IC 50 ) values. KIF23 was elevated in imatinib-resistant tissues and cells of CML. Second, knockdown of KIF23 reduced IC 50 values of imatinib-resistant CML cells to imatinib. Moreover, silence of KIF23 also suppressed cell proliferation and promoted apoptosis of imatinib-resistant CML cells. Third, immunofluorescence analysis showed that the number of LC3 bright spots in imatinib-resistant CML cells was reduced by silence of KIF23. Knockdown of KIF23 upregulated p62 expression and downregulated the expression ratio of LC3-II to LC3-I in imatinib-resistant CML cells. Last, silence of KIF23 decreased nuclear β-catenin and increased cytoplasmic β-catenin in imatinib-resistant CML cells. Activator of Wnt/β-catenin attenuated KIF23 silence-induced increase of apoptosis and decrease of autophagy in imatinib-resistant CML cells. In conclusion, loss of KIF23 repressed autophagy-induced imatinib resistance in CML cells through inactivation of Wnt/β-catenin pathway., (© 2022 John Wiley & Sons Australia, Ltd.)

Sphingolipids (SPLs) are bioactive lipids that manifest structural diversity and complexity in eukaryotes. However, the distributions and functions of these molecules in mammalian tissues/cells have not been systematically investigated. Herein, we integrated shotgun lipidomics with targeted LC-MRM/MS approach to comprehensively analyze SPL species in various biological samples with high accuracy. Preliminarily, 1311 SPL molecules were identified in 18 kinds of mammalian samples, including 3 groups of human sera, 10 mouse tissues and 5 cell lines via 26 sphingoid long-chain bases scanning. The sphingolipidome compositions and distributions were systematically characterized and distinct qualitative and quantitative profiles were clearly exhibited in various samples, indicating unique biological functions of the sphingolipidomes. Next, targeted SPLs analysis by LC-MRM/MS with critical criteria monitoring two characteristic fragments of one precursor was applied to human serum samples from 24 coronary artery disease (CAD) patients and 12 healthy controls, which successfully quantified 170 SPL molecules. Ten novel SPL molecules were discovered as a potential diagnostic panel for CAD patients via multivariate exploratory receiver operating characteristic curve-based biomarker analysis. The diagnostic panel with the 10 SPL molecules achieved 97.2% accuracy, with a favorable auxiliary diagnostic value (AUC = 1.000), for the detection of CAD. These results clearly support the sphingolipidomic approach in application to discovering disease biomarker panel as well as deep investigation of biological functions of complex SPLs in mammalian samples., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Interleukin (IL)-33 is a member of the IL-1 cytokine family, which serves as both a cytokine and a nuclear factor. IL-33 is primarily expressed by keratinocytes, epithelial and endothelial cells, as well as human monocytes, Dendritic cells (DC), and astrocytes. IL-33 has been described as a modulator of inflammation and immune responses, which is mainly associated with the development of T helper 2 (Th2) immunological responses. Cytokines that control the T cells activation have been shown to have a role in the B-cell hyperactivity and production of pathogenic autoantibody isoforms that cause tissue dysfunction in autoimmune disorders. IL-33 levels have been shown to be elevated in a variety of autoimmune disorders, including Rheumatoid arthritis (RA), Systemic lupus erythematosus (SLE), type 1 diabetes (T1D), Multiple sclerosis (MS), and Inflammatory bowel diseases (IBD), suggesting that it may have a role in inducing autoimmunity and inflammatory damage. In addition to pathogenic functions in autoimmune disorders, cytokines may be a promising target for autoimmune disease treatment and follow-up. Therefore, the aim of this study is to review the possibility of using the IL-33/tumorigenicity 2 receptor (ST2) axis as a potential therapeutic target in the treatment of autoimmune disorders., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Pneumatosis cystoides intestinalis (PCI) is a rare disease that most frequently occurs in the large and small intestine and has no obvious clinical symptoms. The main pathological feature is the presence of air-filled cysts in the intestinal submucosa, intermuscular wall, and subserous membrane. Conservative treatment is the first choice when no serious complications are present, whereas timely surgical treatment is needed for serious and life-threatening complications. This report presents the clinical and pathological analysis of PCI in a man in his early 90s. The patient was hospitalized because of acute abdomen and diagnosed with perforation of the sigmoid colon due to PCI with schistosomiasis after emergency surgery. Emergency partial sigmoid colon resection and permanent colostomy were performed under general anesthesia. Preoperative diagnosis of PCI is difficult because of the nonspecific clinical manifestations and endoscopic findings, and missed diagnosis and misdiagnosis easily occur. Pure PCI has no specific symptoms and does not require special treatment, and there is a lack of special treatment methods in clinical practice. However, when PCI is combined with other intestinal diseases such as schistosomiasis enteropathy, intestinal perforation is likely to occur, leading to severe acute abdomen with the need for prompt surgical treatment.

Objectives: There is no effective treatment for occult hepatitis B virus infection (OBI) patients, and immunotherapy may be one of the most promising options. We aim to investigate the underlying mechanism and therapeutic potential of hepatitis B vaccine immunotherapy for OBI patients., Methods: Outpatient OBI patients were screened and randomly divided into treatment (Group A) and control (Group B) groups. At weeks 0, 4, and 24, patients in Group A received a subcutaneous/intramuscular injection of hepatitis B vaccine (Engerix-B, 20 μg/time) according to the standard vaccination schedule; patients in Group B served as blank control. The patients were followed for 36 weeks, with clinical, biochemical, virological, immunological, and imaging data collected and analyzed at weeks 0, 12, 24, and 36, respectively, and the relation between the virology and immunology results was analyzed., Results: Of the 228 OBI patients, 28 were excluded, and 200 were enrolled for observation. In the end, 44 patients were included in Group A and 39 in Group B after excluding lost cases. At week 0 (baseline), some patients in two groups had liver disease symptoms, HBV-related liver function damage, and liver fibrosis. 86.36% (38/44) and 82.05% (32/39) patients were positive for serum hepatitis B surface antibodies (anti-HBs) in Group A and Group B, respectively, with the median (quartile) of 42.47 (16.85, 109.1) and 39.27 (16.06, 117.4) mIU/ml, respectively. Reduced peripheral blood CD4 + T, CD8 + T, and B lymphocytes were found in some patients in two groups. These results were not statistically different between Group A and Group B ( P> 0.05). At week 36, all patients were serum anti-HBs (+) in Group A, with a median (quartile) of 1000 (483.9, 1000) mIU/ml, which was significantly higher than that at week 0 ( P <0.05) and that in Group B ( P <0.05). Compared to week 0, the number of CD8 + T and B lymphocytes increased significantly and were significantly higher than Group B at the same point. Two patients in Group B were found to have hepatitis B virus reactivation from week 12 to week 36., Correlation Analysis: Anti-HBs in Group A patients were positively correlated with B lymphocytes (r=0.3431, 0.3087, and 0.3041, respectively) and positively correlated with CD8 + T lymphocytes (r=0.4954, 0.3054, and 0.3455, respectively) at weeks 12, 24, and 36., Conclusion: Virological reactivation is a risk for OBI patients. Serum hepatitis B surface antibodies were significantly increased after hepatitis B vaccine treatment, the same as the numbers of peripheral blood B and CD8 + T lymphocytes; changes in hepatitis B surface antibody levels were positively correlated with the changes in peripheral blood B and CD8 + T lymphocytes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Peng, Yao, Yuan, Liu, Xia, He, Li and Yao.)

A precise balance between sleep and wakefulness is essential to sustain a good quality of life and optimal brain function. GABA is known to play a key and conserved role in sleep control, and GABAergic tone should, therefore, be tightly controlled in sleep circuits. Here, we examined the role of the astrocytic GABA transporter (GAT) in sleep regulation using Drosophila melanogaster. We found that a hypomorphic gat mutation (gat 33-1 ) increased sleep amount, decreased sleep latency, and increased sleep consolidation at night. Interestingly, sleep defects were suppressed when gat 33-1 was combined with a mutation disrupting wide-awake (wake), a gene that regulates the cell-surface levels of the GABA A receptor resistance to dieldrin (RDL) in the wake-promoting large ventral lateral neurons (l-LNvs). Moreover, RNAi knockdown of rdl and its modulators dnlg4 and wake in these circadian neurons also suppressed gat 33-1 sleep phenotypes. Brain immunohistochemistry showed that GAT-expressing astrocytes were located near RDL-positive l-LNv cell bodies and dendritic processes. We concluded that astrocytic GAT decreases GABAergic tone and RDL activation in arousal-promoting LNvs, thus determining proper sleep amount and quality in Drosophila., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Up to now, it has not been clear whether occult hepatitis B virus (HBV) infection (OBI) can be treated with antiviral therapy whether OBI can develop drug resistance gene mutation or not. We report a middle-aged female patient with OBI who showed HBV reactivation (HBVr) during more than 3 years of intermittent entecavir (ETV) antiviral therapy: seropositive HBV surface antigen (HBsAg), increased e antigen (HBeAg), and repeatedly elevated serum HBV DNA. Genotype analysis showed that the patient was infected with HBV type B. Genetic sequencing of HBV showed the mutants of S143T, D144G, and G145R in the S gene region, and the mutant of site 1896 in the pre-Core region coexisted with the wild type (G1896A/G). No mutation was found in other HBV gene segments. Drug resistance gene analysis found RtL229W mutant, resistant to lamivudine but sensitive to ETV and other nucleoside analogs. This case of OBI provides us with the following clinical experiences: Firstly, it is necessary to detect HBV genotype, mutation, and drug-resistant genes at the initial diagnosis, which can be helpful for reasonable treatment. Secondly, identifying the risk factors and mechanisms associated with HBVr could help quantify the risk of HBVr and manage the clinical consequences. Thirdly, the OBI patients with hepatitis B e antigen-positive, HBV DNA > 1 × 10 3  IU/ml should be recommended regular and continuous antiviral therapy as soon as possible to prevent the occurrence of hepatocirrhosis and hepatocellular carcinoma (HCC)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yuan, Peng, Xia, He, Qiu and Yao.)

The quantity of tightly bound extracellular polymeric substances (TB-EPS) and loosely bound extracellular polymeric substances (LB-EPS) are recognized to be crucial for activated sludge flocculability and settleability. However, the generation and consumption mechanisms of TB-EPS and LB-EPS are vague, and there is no effective model to quantitatively predict LB-EPS and TB-EPS. In this work, a decrease in LB-EPS and TB-EPS was verified to increase the absolute value of the zeta potential and decrease the sludge settling volume, which affects the flocculation and settling performance of sludge. Hence, we comparatively developed, calibrated and validated two different mathematical model structure (named expanded unified model-TL1 and expanded unified model-TL2), aiming to systematically reveal the generation and consumption mechanism of TB-EPS and LB-EPS and quantitatively predict changes of TB-EPS and LB-EPS. On the basis of microbial physiology and the existing literature, two different mechanisms of the generation and consumption of TB-EPS and LB-EPS are described. According to the validation performed, expanded unified model-TL2 fit better with experimental TB-EPS and LB-EPS, which described with the hypotheses: (i) TB-EPS and LB-EPS are simultaneously generated while activate biomass growth on external substrate, (ii) LB-EPS can also be hydrolyzed by TB-EPS, and (iii) Biomass-associated products (BAP) are hydrolyzed by LB-EPS, and it was further proven to be more realistic from the perspective of microbial physiology. This study systematically revealed the generation and consumption mechanism of TB-EPS and LB-EPS by mathematical modeling, and provides a basis for regulating the concentrations of them to improve sludge settling capacity and system stability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In recent years, influenced by the legalization of Cannabis sativa in some countries and regions, the number of people who smoke or abuse C. sativa has continuously grown, cases of transnational C. sativa trafficking have also been increasing. Therefore, fast and accurate identification and source tracking of C. sativa have become urgent social needs. In this study, we developed a new 19-plex short tandem repeats (STRs) typing system for C. sativa , which includes 15 autosomal STRs (D02-CANN1, C11-CANN1, 4910, B01-CANN1, E07-CANN1, 9269, B05-CANN1, H06-CANN2, 5159, nH09, CS1, ANUCS 305, 3735, and ANUCS 302 and 9043), two X-chromosome STRs (ANUCS 501 and 1528), one sex-determining marker (DM016, on Y-chromosome), and a quality control marker (DM029, on autosome). The whole polymerase chain reaction (PCR) process could finish within 1 h, making the system suitable for fast detection. The PCR products were detected and separated with an Applied Biosystems 3500 XL Genetic Analyser. Developmental validation studies indicated that the 19-plex typing system was accurate, reliable and sensitive, which could also deconvolute mixed C. sativa samples. Specifically, the sensitivity study showed that a full genotyping profile was obtainable with as low as 125 pg of C. sativa DNA. The species specificity study demonstrated that this multiplex has no cross-reactivity with common non C. sativa DNA. In the population study, a total of 162 alleles at 15 autosomal STRs and 14 alleles at two X-chromosome STRs were detected among 85 samples. The efficiency parameters, including the total discrimination power (TDP) and the combined power of exclusion (CPE) of the system, were calculated to exceed 0.999 999 999 999 988 and 0.998 455 889 684 078, respectively, further proving that the system could meet the needs of individual identification. To the extent of the known studies, this is the first study that included the C. sativa sex-determining marker. In conclusion, the developed new 19-plex STR typing system can successfully achieve the purposes of species identification, gender determination, and individual identification, which could be a powerful tool in tracing trade routes of particular drug syndicates or dealers or in linking certain C. sativa to a crime scene., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xia, Tao, Qu, Zhang, Yu, Yuan, Zhang and Li.)

Background: It is unknown how many people in China have chronic occult hepatitis B virus (HBV) infection (OBI) [chronic HBV infection with negative serum hepatitis B surface antigen (HBsAg) (N-HBsAg)]. Their clinical and virological characteristics, especially the correlation between the OBI and hepatocellular carcinoma (HCC), are still elusive and need to be investigated, including prevention, early diagnosis, and treatment strategies., Methods: 138 patients with HCC related to OBI were screened from 698 patients of HCC associated with HBV infection, their characteristics of epidemiology, clinical, biochemistry, virology, diagnostics, and therapeutics were analyzed retrospectively. Furthermore, the correlation between virological features and clinical features was investigated., Results: It was found that 19.8% (138/698) of patients with HBV-related HCC were OBI, of which 79.7% (110/138) were men, and 20.3% (28/138) were women. Most of the patients with OBI-related HCC were older men, and the median age was 63.2 years. In total 78.3% (108/138) of the patients had apparent right upper abdomen discomfort and/or pain and then sought medical examination, while 21.7% (30/138) of the patients were identified by health examination. A total of 10.9% (15/138) of the patients were admitted with chronic infection of HBV, and 2.2% (3/138) of the patients were admitted with a family history of hepatitis B. The alpha-fetoprotein (AFP) serum-positive rate was 39.1% (54/138). Tumor lesions >5.0 cm, with intrahepatic and/or extrahepatic metastasis, were found in 72.5% (100/138) of the patients. The diameter of the tumor in the Group of hepatitis B core antibody-positive [HBcAb(+)] and hepatitis B surface antibody-positive [HBsAb(+)] was 7.03 ± 3.76 cm, which was much smaller than 8.79 ± 4.96 cm in the Group of HBcAb(+) and HBsAb(-) ( P = 0.035)., Conclusion: It is estimated that at least 21 million OBI patients live in China. HBcAb(+) was not only the evidence of chronic HBV infection but also a dangerous mark for surface antigen-negative patients. A semi-annual or annual medical checkup is essential for all OBI patients to identify HCC as early as possible. The hypothesis underlying our analysis was that hepatitis B surface antibody would prevent the progress of HCC and facilitate the clearance of HBV in patients with OBI. Thereby, the hepatitis B vaccine could be used to prevent severe disease consequences., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xia, Peng, He, Jiang, Yuan, Liu and Yao.)

Objective: To study the clinical diagnostic value of contrast-enhanced ultrasound (CEUS) in bladder occupied lesions., Methods: 38 cases of conventional-ultrasound-found bladder occupied lesions did color Doppler flow imaging (CDFI) and CEUS checks. By comparing the difference between two types of blood flow imaging technologies in displaying the flow of bladder occupied lesions and observing the perfusion modes of contrast agents to enter lesions, the perfusion characteristics of CEUS were analyzed. Finally, they were contrasted with the surgical pathology results., Results: Of all the 38 cases, there were 51 bladder occupied lesions, including 43 bladder malignant tumors, 2 bladder inverted papillomas, and 6 glandular cystitis lesions. The blood flow display rate of bladder occupied lesions was 100% using CEUS. Apparently, it was higher than that of CDFI (62.7%), and the result of these showed a statistically significant difference ( P < 0.05). Using CEUS, 46 malignant lesions and 5 glandular cystitis lesions were indicated, and the diagnostic accuracy rate was 86.3%., Conclusion: CEUS can improve the blood flow display rate of bladder occupied lesions, and it can also observe the real-time blood flow of these lesions. It can help judge their nature and has a higher clinical value in differentiating the benign from the malignant., Competing Interests: The authors declare no competing financial interests., (Copyright © 2021 Qiping Liu et al.)

Objective: To discuss the clinical application value of contrast-enhanced ultrasound (CEUS) in testicular occupied lesions., Methods: Nine conventional-ultrasound-found testicular occupied lesions which underwent CEUS meantime were analyzed retrospectively. The CEUS perfusion pattern was compared with the surgical pathological result or follow-up findings., Results: Among all the 9 testicular occupied lesions, there were 5 testicular malignant tumors, 1 testicular benign tumor, 1 testicular tuberculosis, and 2 testicular hematomas. CEUS diagnosed 6 testicular malignant tumors, 1 testicular benign tumor, and 2 testicular hematomas, and its diagnostic accuracy was about 88.9%., Conclusion: CEUS has high clinical application value in the differential diagnoses of benign and malignant testicular occupied lesions., Competing Interests: The authors declare no competing financial interests., (Copyright © 2021 Qiping Liu et al.)

Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) are implicated in cerebral ischemia reperfusion (I/R) injury process. In this study, after extraction and identification of human umbilical cord MSCs (HMCs)-derived EVs, I/R rat models were established and treated with HMC-EVs to measure pathological damage, apoptosis and inflammation in brain tissues. The differentially expressed microRNAs (miRs) in HMC-EVs and I/R rat tissues were screened. The downstream gene and pathways of miR-24 were analyzed. The gain- and loss-of function of miR-24 in HMC-EVs was performed in I/R rat models and hypoxia/reoxygenation (H/R) cell models. SH-SY5Y cells were subjected to hypoxia and biological behaviors were detected by MTT assay, colony formation experiment, EdU staining and Transwell assays, and cells were incubated with the inhibitors of downstream pathways. As expected, infarct size, brain tissue apoptosis and inflammation were decreased after HMC-EVs treatment. miR-24 overexpression in HMC-EVs reduced I/R injury, while miR-24 knockdown in HMC-EVs impaired the protective roles of HMC-EVs in I/R injury. HMC-EVs-carried miR-24 could target AQP4 to activate the P38 MAPK/ERK1/2/P13K/AKT pathway, and thus promoted the proliferation and migration of SH-SY5Y cells after H/R injury, which were reversed by LY294002 and PD98095. Taken together, HMC-EVs-carried miR-24 played protective roles in I/R injury, possibly by targeting AQP4 and activating the P38 MAPK/ERK1/2/P13K/AKT pathway. This study may offer novel perspective for I/R injury treatment.

Objective: The objective of this present research is to evaluate the effect of the intervention of enhancing quality of life in patients in patients with advanced lung cancer., Methods: Our research is carried out as a randomized clinical trial which will be implemented from December 2020 to October 2021. It was approved by the Ethics Committee of People's Hospital of Chengyang District (03982790). This study includes 90 patients with advanced lung cancer. Patients diagnosed at our oncology clinic are eligible if they are diagnosed within 8 weeks of a novel diagnosis of stage 3 or stage 4 lung cancer. Patients with hepatic insufficiency, renal failure, and respiratory and heart failure, as well as a series of severe mental illness are excluded from our research. Patients are divided randomly into the intervention group and control group, each group is assigned 45 patients. Through utilizing functional assessment of cancer therapy-lung, the measurement of life quality is conducted. And the measurement of mood is carried out with Hospital Anxiety and Depression Scale., Results: Table 1 indicates the patient's life quality and Hospital Anxiety and Depression Scale in both groups., Conclusion: Enhancing quality of life in patient intervention may be beneficial to improve the life quality in advanced lung cancer patients.Trial registration: The protocol was registered in Research Registry (researchregistry6243)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.)

Increasing evidence suggests that circular RNAs are emerging biomarkers or targets for early cancer diagnosis and treatment. However, the studies of circular RNA in osteosarcoma (OS) are limited. In this study we found that circ&#95;ARF3 were highly expressed in osteosarcoma cell lines and tumor tissues. Knocking down circ&#95;ARF3 greatly ceased OS cell growth, impaired cell colony formation and halted cell cycle transition from G1 to S phase. Bioinformatic analysis suggested that miR-1299 is the target of circ&#95;ARF3. Luciferase assay and biotin labeled circ&#95;ARF3 pull down assay confirmed their interactions in OS cells. The regulatory roles of circ&#95;ARF3 on miR-1299 was also investigated. Further bioinformatic analysis showed that CDK6 is the target of miR-1299. Overexpressing miR-1299 in OS cells decreased CDK6 expression and arrested OS cell growth and cell cycle progression. However, the roles of miR-1299 in regulating CDK6 expression, OS cell growth and cell cycle progression were greatly impaired in the presence of circ&#95;ARF3. In general, our study demonstrated that in the OS, highly expressed circ&#95;ARF3 acts as a sponge of miR-1299 to inhibit miR-1299 mediated CDK6 downregulation which further promoted OS pathogenesis. circ&#95;ARF3 could be a potential target for OS treatment in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020. Published by Elsevier Inc.)

Recent studies have suggested that circular RNAs play an important role in the progression of various cancers. However, few studies have revealed the great value of circRNAs in the diagnosis and prognosis prediction of osteosarcoma (OS). In this study, we performed experiments with the human OS cell lines and the results showed that the expression of circHIPK3 in OS cell lines was significantly upregulated compared to that in the normal cell line. In addition, the results showed that circHIPK3 could promote the migration, invasion, and growth of OS cells. Furthermore, miR-637 was identified as a target of circHIPK3, while STAT3 was targeted by miR-637. circHIPK3 could promote STAT3 expression via interacting with miR-637 in OS cells. In conclusion, our research uncovered an important role of the circHIPK3/miR-637/STAT3 pathway in the migration and invasion of OS cells and suggested that circHIPK3 may be a prognostic marker and a promising therapeutic target for OS., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Zhongyue Huang et al.)

Estrogen evidently exerts a protective role against gastric cancer. Accordingly, we evaluated the relationship between the expression of the estrogen receptor ER-α36 and the clinicopathologic features in gastric cancer. ER-α36 expression levels differed among the tumor center, invasion front, and vascular metastases. The effects of E2β (17β-Estradiol, E2β) on invasion ability in SGC7901, High36 (with ER-α36 upregulation), and Low36 (with ER-α36 downregulation) cells were evaluated using Transwell assays. Furthermore, the c-Src signaling pathway was inhibited using PP2 and the effects on E2β-induced increases in E-cadherin, MMP2, and MMP9 were evaluated using western blotting. ER-α36, c-Src, MMP2, and E-cadherin levels were also evaluated in tumor xenografts. We found that 0.1 nM E2β promoted gastric cancer cell invasion by reducing E-cadherin expression and increasing MMP2 and MMP9 levels. The upregulation of ER-α36 promoted gastric cancer cell invasion and the downregulation of ER-α36 reduced the invasive ability of cells. The levels of ER-α36, c-Src, and MMP2 were the highest in tumor xenografts using High36 cells, intermediate in tumor xenografts using SGC7901 cells, and lowest in tumor xenografts using Low36 cells. The opposite results were obtained for E-cadherin expression. ER-α36 enhanced gastric cancer cell invasion by the activation of membrane-initiated c-Src signaling pathways. In particular, treatment with E2β and ER-α36 influenced gastric cancer cell invasion. Furthermore, c-Src was involved in the ER-α36-mediated estrogen signaling pathway and cell invasion., Competing Interests: None., (IJCEP Copyright © 2020.)

Background and Aim: Our study aimed to investigate the ways by which HOXB7 affects gastric cancer progression and oxaliplatin (L-OHP) resistance., Methods: First, the expression of HOXB7 in paired cancer and paracancerous tissues of L-OHP-sensitive and L-OHP-resistant gastric cancer patients was qualitatively and quantitatively analyzed by immunohistochemistry. Then, the expression of HOXB7 in these tissues was further quantitatively analyzed at protein and transcriptional levels. The expression of HOXB7 in the SGC-7901 L-OHP-resistant gastric cancer cell line was further verified by immunofluorescence, western blot, and RT-qPCR. In addition, by transfecting the SGC-7901 cell line, control (sh-con) and HOXB-7-silenced (sh-HOXB7) gastric cancer cell lines were created. Subsequently, the migratory and invasive abilities of these cells were determined by the transwell assay. The proliferation rate of both control and HOXB-7-silenced cells induced by varying concentrations of L-OHP was detected by the CCK-8 assay, while the degree of apoptosis in the same cells induced by 60 µM L-OHP was detected by flow cytometry., Results and Conclusion: Results suggested that HOXB7 was overexpressed in both the tissues of L-OHP-resistant gastric cancer patients and the SGC-7901 gastric cancer cell line. Moreover, HOXB7 promoted the migratory and invasive abilities of gastric cancer cells. By silencing HOXB7 protein expression, the proliferation rate of L-OHP-resistant gastric cancer cells decreased considerably, while their degree of apoptosis increased significantly. These results showed that HOXB7 promoted gastric cancer progression and L-OHP resistance., Competing Interests: None., (IJCEP Copyright © 2020.)

Objective : To investigate maternal plasma concentrations of tissue kallikrein (TK) in normal and preeclamptic pregnancies. Methods : 96 women with singleton pregnancies were categorized into normal, mild preeclampsia and preeclampsia with severe features. Plasma levels of TK were quantified by ELISA and left lateralrecumbencyposition BP measured. Results : Maternal plasma TK concentrations were significantly lower in preeclampsia with severe features compared with mild preeclampsia and normal pregnant. Plasma TK concentrations were negatively correlated with systolic and diastolic blood pressure, and 24-hour urine protein. Conclusion : Lower maternal plasma TK may be a risk marker that reflects the severity of preeclampsia.

In this paper, we report the first successful demonstration of the direct growth of high-quality two-dimensional (2D) MoS 2 semiconductors on a flexible substrate using a 25-μm-thick Yttria-stabilized zirconia ceramic substrate. Few-layered MoS 2 crystals grown at 800 °C showed a uniform crystal size of approximately 50 μm, which consisted of about 10 MoS 2 layers. MoS 2 crystals were characterized using energy-dispersive X-ray spectroscopy. Raman spectroscopy was performed to investigate the crystal quality under bending conditions. The Raman mapping revealed a good uniformity with a stable chemical composition of the MoS 2 crystals. Our approach offers a simple and effective route to realize various flexible electronics based on MoS 2 . Our approach can be applied for MoS 2 growth and for other 2D materials. Therefore, it offers a new opportunity that allows us to demonstrate high-performance flexible electronic/optoelectronic applications in a less expensive, simpler, and faster manner without sacrificing the intrinsic performance of 2D materials.

Background: Chronic exposure to ambient particulate matter with aerodynamic diameters < 2.5 (PM2.5) induces oxidative injury and liver pathogenesis. The present study assessed the effect and mechanism of long-term, real-world airborne particulate matter (PM) exposure on oxidative stress and hepatic steatosis in the context of a standard chow diet (STD) and a high-fat diet (HFD); the study further explored whether a combination of PM exposure and HFD treatment exacerbates the adverse effects in mice., Methods: C57BL/6J mice fed with STD or HFD (41.26% kcal fat) were exposed to PM or filtered air (FA) for 5 months. Lipid metabolism, oxidative stress and liver pathogenesis were evaluated. Real-time PCR and western blotting were performed to determine gene expression and molecular signal transduction in liver., Results: Chronic airborne PM exposure impaired oxidative homeostasis, caused inflammation and induced hepatic steatosis in mice. Further investigation found that exposure to real-world PM increased the expression of hepatic Nrf2 and Nrf2-regulated antioxidant enzyme gene. The increased protein expression of the sterol regulatory element binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) in the liver were also observed in PM-exposed groups. Furthermore, the combination of PM exposure and HFD treatment caused a synergistic effect on the changes of lipid accumulation oxidative stress, inflammation in the mouse liver., Conclusions: Through in vivo study, we reveal that the combination of real-world ambient PM exposure and HFD treatment aggravates hepatic lipid metabolism disorders, inflammation and oxidative stress. PM exposure may accelerate the progression to non-alcoholic steatohepatitis by regulating SREBP-1c/FAS regulatory axis., Competing Interests: The authors have declared that no competing interests exist.

Background: Ovarian cancer is a common gynecologic malignancy with poor prognosis, requiring innovative new therapeutic strategies. Temperature-controlled drug delivery to cancer cells represents a novel, promising, targeted treatment approach., Objective: We prepared folate receptor-targeted thermosensitive liposomes wrapped with the HSP90 inhibitor 17-AAG and superparamagnetic material (17-AAG/MTSLs-FA), and tested the efficacy of these targeted magnetoliposomes in vitro and in vivo., Methods: Magnetic thermosensitive liposomes wrapped with 17-AAG were coprecipitated with Fe 3 O 4 magnetic nanoparticles and prepared by a rotary evaporation method. Experiments were conducted with SKOV3 human ovarian cancer cells and MCF7 human breast carcinoma cells to evaluate the anti-tumor effects., Results: 17-AAG/MTSLs-FA prepared in this study met the basic requirements for therapeutic application. The preparation method is relatively simple and the raw materials are readily available. The product exhibited strong magnetism, high encapsulation efficiencies, and satisfactory performance. The liposomes combined with hyperthermia significantly inhibited the proliferation of SKOV3 cells and induced apoptosis. Experiments using a mouse subcutaneous model as well as an ascites tumor xenograft model indicated that 17-AAG/MTSLs-FA was stable in vivo and effectively targeted tumor tissues expressing the folate receptor., Conclusions: Folic acid-conjugated 17-AAG magnetic thermosensitive liposomes in combination with an alternating magnetic field for heating can achieve a synergistic anti-tumor effect of chemotherapy and heat treatment, potentially offering a new method for ovarian cancer treatment.

Background: The diapause hormone (DH) has been shown either to induce or to terminate diapause, depending on the insect species. In a previous study we demonstrated that the DH from Clostera anastomosis (caDH) has biological activity in Helicoverpa armigera, which prompted us to examine the potential growth-inhibiting or antiherbivory effects of the TAT-caDH fusion protein when expressed in transgenic plants., Results: In this study, we produced transgenic tobacco plants expressing either the TAT-caDH protein or a TAT-caDH-eGFP fusion version that allowed tracking of the fluorescent protein in plant tissues. Our results indicate that H. armigera larvae feeding on transgenic tobacco expressing TAT-caDH exhibited a significantly reduced survival rate and weight gain. However, larvae feeding on transgenic tobacco expressing TAT-caDH-eGFP were unaffected. While fusion of the eGFP gene influenced the bioactivity of caDH in larvae, TAT-caDH-eGFP can still penetrate the insect midgut cell membrane., Conclusion: TAT-caDH increases DH stability in oral delivery. Our results may help in targeting DH-dependent physiological processes in insects for improving herbivore tolerance in economically important crops. © 2016 Society of Chemical Industry., (© 2016 Society of Chemical Industry.)

Insect kinins were shown to have diuretic activity, inhibit weight gain, and have antifeedant activity in insects. In order to study the potential of the TAT-fusion approach to deliver diuretic peptides per os to pest insects, the HezK I peptide from Helicoverpa zea , as a representative of the kinin family, was selected. The fusion gene TAT-HezK I was designed and was used to transform tobacco plants. As a means to further improve the stability of TAT-HezK I, a fusion protein incorporating HezK I, transactivator of transcription (TAT), and the cowpea trypsin inhibitor (CpTI) was also designed. Finally, the toxicity of the different tobacco transgenic strains toward Helicoverpa armigera was compared. The results demonstrated that TAT-HezK I had high toxicity against insects via transgenic expression of the peptide in planta and intake through larval feeding. The toxicity of the fusion TAT-HezK I and CpTI was higher than the CpTI single gene in transgenic tobacco, and the fusion TAT-HezK I and CpTI further enhanced the stability and bioavailability of agents in oral administration. Our research helps in targeting new genes for improving herbivore tolerance in transgenic plant breeding., Competing Interests: The authors declare no conflict of interest.

Diapause hormone (DH), which can terminate diapause in Helicoverpa armigera Hübner (Lepidoptera: Noctuidae), has shown promise as a pest control method. However, the main challenge in using DH as an insecticide lies in achieving effective oral delivery, since the peptide may be degraded by digestive enzymes in the gut. To improve the efficacy of oral DH application, the Clostera anastomosis (L.) (Lepidoptera: Notodontidae) diapause hormone (caDH) was fused to the Protein Transduction Domain (PTD) of the human immunodeficiency virus-1 transactivator of transcription (TAT). Cellular transduction of TAT-caDH was verified with the use of a green fluorescent protein fusion, and its ability to terminate diapause was verified by injection into diapausing H. armigera pupae. Orally administered TAT-caDH resulted in larval growth inhibition. In TAT-caDH-treated insects, larval duration was delayed and the pupation rates were decreased at both development promoting conditions [27 °C, a photoperiod of 14:10(L:D) h] and diapause inducing conditions [20 °C, a photoperiod of 10:14(L:D) h]. No significant difference in diapause rate was observed between the TAT-caDH-treated and caDH-treated or control pupae maintained at diapause inducing conditions. Our results show that treatment with a recombinant TAT-caDH protein can affect larval development in H. armigera, and it suggest that TAT-DH treatment may be useful for controlling pests. This study is the first record of oral DH application in insect., (© The Author 2015. Published by Oxford University Press on behalf of the Entomological Society of America.)

Objective: To investigate the role of DNA methylation in the regulation of matrix metalloproteinase 9 (MMP-9) gene expression in endometriosis., Methods: MMP-9 gene methylation status in eutopic and ectopic endometria were analyzed by methylation specific PCR. The expression of MMP-9 protein in eutopic and ectopic endometria were detected by immunohistochemistry. We prepared the primary cultured ectopic endometrial stromal cells, and then examined the gene expression and methylation status of MMP-9 after the culture cells were treated with 5-Aza-2-deoxycytidine., Results: The expression of MMP-9 in ectopic endometrial stromal cells was significantly higher than that in eutopic endometrium. MMP-9 methylation level was lower in ectopic endometrium. After treated with 5-Aza-dC, endometriosis cells showed elevated MMP-9 gene expression and methylation level., Conclusion: DNA methylation at the promoter region of MMP-9 gene can enhance the expression of MMP-9 in ectopic endometrial stromal cells of endometriosis.

A negative transcriptional feedback loop generates circadian rhythms in Drosophila. PERIOD (PER) is a critical state-variable in this mechanism, and its abundance is tightly regulated. We found that the Drosophila homolog of ATAXIN-2 (ATX2)--an RNA-binding protein implicated in human neurodegenerative diseases--was required for circadian locomotor behavior. ATX2 was necessary for PER accumulation in circadian pacemaker neurons and thus determined period length of circadian behavior. ATX2 was required for the function of TWENTY-FOUR (TYF), a crucial activator of PER translation. ATX2 formed a complex with TYF and promoted its interaction with polyadenylate-binding protein (PABP). Our work uncovers a role for ATX2 in circadian timing and reveals that this protein functions as an activator of PER translation in circadian neurons.

Physical activity improves learning and hippocampal neurogenesis. It is unknown whether compounds that increase endurance in muscle also enhance cognition. We investigated the effects of endurance factors, peroxisome proliferator-activated receptor δ agonist GW501516 and AICAR, activator of AMP-activated protein kinase on memory and neurogenesis. Mice were injected with GW for 7 d or AICAR for 7 or 14 d. Two weeks thereafter mice were tested in the Morris water maze. AICAR (7 d) and GW improved spatial memory. Moreover, AICAR significantly, and GW modestly, elevated dentate gyrus neurogenesis. Thus, pharmacological activation of skeletal muscle may mediate cognitive effects.

Exercise benefits both general health and brain function in rodents and humans. However, it is less clear whether physical activity prevents or ameliorates neurodegenerative diseases. The aim of the present study was to determine whether voluntary wheel running can delay the onset or reduce the severity of Huntington's disease (HD) in a mouse model. To investigate whether running may delay HD symptoms lifespan, disease onset, locomotor activity, glucose levels, weight, striatal volume, inclusions, cognition and hippocampal neurogenesis were studied in male N171-82Q transgenic HD mice. Running started in pre-symptomatic (44±1 days old) male HD mice, did not improve function and appeared to accelerate disease onset. In particular, HD runners had an earlier onset of disease symptoms (shaking, hunched back and poor grooming), reduced striatal volume and impaired motor behavior, including a shorter latency to fall from the rotarod compared to sedentary controls. Furthermore, weight loss, reduced lifespan, hyperglycemia, Morris water maze learning deficits, diminished hippocampal neurogenesis, deficits in immature neuronal morphology, intranuclear inclusions and decreased dentate gyrus volume were refractory to physical activity. Taken together our research indicates that exercise is not beneficial, and may be detrimental to a vulnerable nervous system.

Dopamine is an important neuromodulator in animals and its roles in mammalian sexual behavior are extensively studied. Drosophila as a useful model system is widely used in many fields of biological studies. It has been reported that dopamine reduction can affect female receptivity in Drosophila and leave male-female courtship behavior unaffected. Here, we used genetic and pharmacological approaches to decrease the dopamine level in dopaminergic cells in Drosophila, and investigated the consequence of this manipulation on male homosexual courtship behavior. We find that reduction of dopamine level can induce Drosophila male-male courtship behavior, and that this behavior is mainly due to the increased male attractiveness or decreased aversiveness towards other males, but not to their enhanced propensity to court other males. Chemical signal input probably plays a crucial role in the male-male courtship induced by the courtees with reduction of dopamine. Our finding provides insight into the relationship between the dopamine reduction and male-male courtship behavior, and hints dopamine level is important for controlling Drosophila courtship behavior.

Sexual behavior between males is observed in many species, but the biological factors involved are poorly known. In mammals, manipulation of dopamine has revealed the role of this neuromodulator on male sexual behavior. We used genetic and pharmacological approaches to manipulate the dopamine level in dopaminergic cells in Drosophila and investigated the consequence of this manipulation on male-male courtship behavior. Males with increased dopamine level showed enhanced propensity to court other males but did not change their courtship toward virgin females, general olfactory response, general gustatory response, or locomotor activity. Our results indicate that the high intensity of male-male interaction shown by these manipulated males was related to their altered sensory perception of other males.

Odors elicit a number of behavioral responses, including attraction and repulsion in Drosophila. In this study, the authors used a T-maze apparatus to show that wild-type Drosophila melanogaster exhibit a robust circadian rhythm in the olfactory attractive and repulsive responses. These responses were lower during the day and began to rise at early night, peaking at about the middle of the night and then declining thereafter. They were also independent of locomotor activity. The olfactory response rhythms were lost in period or timeless mutant flies (per0, tim0), indicating that clock genes control circadian rhythms of olfactory behavior. The rhythms in olfactory response persisted in the absence of the pigment-dispersing factor neuropeptide or the central pacemaker lateral neurons known to drive circadian patterns of locomotion and eclosion. These results indicate that the circadian rhythms in olfactory behavior in Drosophila are driven by pacemakers that do not control the rest-activity cycle and are likely in the antennae.

Drosophila amyloid precursor-like protein (APPL) is expressed extensively in the nervous system soon after neuronal differentiation. By utilizing different transgenic flies, we studied the physiological function of two APPL protein forms, membrane-bound form (mAPPL) and secreted form (sAPPL), in neural development. We found that neither deletion nor overexpression of APPL protein altered the gross structure of mushroom bodies in the adult brain. No changes were detected in cell types and their relative ration in embryo-derived cultures from all APPL mutants. However, the neurite length was significantly increased in mutants overexpressing mAPPL. In addition, mutants lacking sAPPL had numerous neurite branches with abnormal lamellate membrane structures (LMSs) and blebs, while no apoptosis was detected in these neurons. The abnormal neurite morphology was most likely due to the disorganization of the cytoskeleton, as shown by double staining of actin filaments and microtubules. Electrophysiologically, A-type K+ current was significantly enhanced, and spontaneous excitatory postsynaptic potentials (sEPSPs) were greatly increased in APPL mutants lacking sAPPL. Moreover, panneural overexpression of different forms of APPL protein generated different defects of wings and cuticle in adult flies. Taken together, our results suggest that both mAPPL and sAPPL play essential roles in the development of the central nervous system and nonneural tissues., (copyright (c) 2004 Wiley Periodicals, Inc.)