Brachytherapy in craniopharyngiomas: a systematic review and meta-analysis of long-term follow-up.

OBJECTIVE: Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been clarified. The purpose of this work was to conduct a meta-analysis to analyze the long-term efficacy and adverse reactions profile of brachytherapy for CPs. MATERIALS AND METHODS: The relevant databases were searched to collect the clinical trials on brachytherapy in patients with CPs. Included studies were limited to publications in full manuscript form with at least 5-year median follow-up, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis. RESULTS: According to the inclusion and exclusion criteria, a total of 6 clinical trials involving 266 patients with CPs were included in this meta-analysis. The minimum average follow-up was 5 years. The results of the meta-analysis showed that 1-year, 2-3 years and 5 years progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62% (95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively. At the last follow-up, less than 16% of patients with visual outcomes worser than baseline in all included studies. While, for endocrine outcomes, less than 32% of patients worser than baseline level. CONCLUSION: In general, based on the above results, brachytherapy should be considered as a good choice for the treatment of CP.

The allostery and modification of hGHRH molecules and specific dimer produced significant fertility effect by proliferating and activating in-situ ovarian mesenchymal stem cells.

The negative coordination of growth hormone secretagogue receptor (GHS-R) and growth hormone-releasing hormone receptor (GHRH-R) involves in the repair processes of cellular injury. The allosteric U- or H-like modified GHRH dimer Grinodin and 2Y were comparatively evaluated in normal Kunming mice and hamster infertility models induced by CPA treatment. 1-3-9 µg of Grinodin or 2Y per hamster stem-cell-exhaustion model was subcutaneously administered once a week, respectively inducing 75-69-46 or 45-13-50 % of birth rates. In comparison, the similar mole of human menopausal gonadotropin (hMG) or human growth hormone (hGH) was administered once a day but caused just 25 or 20 % of birth rates. Grinodin induced more big ovarian follicles and corpora lutea than 2Y, hMG, hGH. The hMG-treated group was observed many distorted interstitial cells and more connective tissues and the hGH-treated group had few ovarian follicles. 2Y had a plasma lifetime of 21 days and higher GH release in mice, inducing lower birth rate and stronger individual specificity in reproduction as well as only promoting the proliferation of mesenchymal-stem-cells (MSCs) in the models. In comparison, Grinodin had a plasma lifetime of 30 days and much lower GH release in mice. It significantly promoted the proliferation and activation of ovarian MSCs together with the development of follicles in the models by increasing Ki67 and GHS-R expressions, and decreasing GHRH-R expression in a dose-dependent manner. However, the high GH and excessive estrogen levels in the models showed a dose-dependent reduction in fertility. Therefore, unlike 2Y, the low dose of Grinodin specifically shows low GHS-R and high GHRH-R expressions thus evades GH and estrogen release and improves functions of organs, resulting in an increase of fertility.

Blood Lipid Disorders in Post-Operative Craniopharyngioma Children and Adolescents and the Improvement with Recombinant Human Growth Hormone Replacement.

Context: The high prevalence of hypothalamic obesity (HO) and dyslipidemia in individuals with craniopharyngioma (CP) following surgery is a cause for increasing concern. However, few studies have explored the lipid profile in pediatric CP patients, with inconsistent findings. In addition, the role of recombinant human growth hormone (rhGH) replacement remains unclear in these patients. Objective: To compare the blood lipid profile among post-operative craniopharyngioma children and adolescents with that among healthy controls and to reveal the effects of rhGH replacement. Methods: Data of 79 post-operative craniopharyngioma children and adolescents in our center were retrospectively collected. Sixty patients underwent rhGH replacement during the follow-ups. We selected 36 patients who received rhGH replacement therapy, while 20 patients received rhGH replacement for at least 1 year and had complete lipid data before and after treatment and compared them with 19 patients who did not receive rhGH replacement therapy. Results: Craniopharyngioma patients had higher total cholesterol (TC) (5.17 vs 3.77 mmol/L), triglyceride (TG) (1.51 vs 0.73 mmol/L), and low-density lipoprotein cholesterol (LDL-C) (3.14 vs 2.10 mmol/L), and lower high-density lipoprotein cholesterol (HDL-C) (1.06 vs 1.39 mmol/L) than controls (all p < 0.001). The lipid profile of obese and non-obese patients was not significantly different. After rhGH replacement, TC was 0.90 mmol/L lower (p = 0.002) and LDL-C was 0.73 mmol/L lower (p = 0.010) than baseline. Although the baseline LDL-C was higher, patients with rhGH replacement had lower LDL-C (-0.73 mmol/L adjusted for age and sex, p = 0.045) after the initiation of replacement compared with patients without rhGH replacement. Conclusion: The lipid profile of obese and non-obese children and adolescents with craniopharyngioma was unfavorable, and rhGH replacement could improve their lipid profile.

Plantamajoside Alleviates Substantia Nigra Damage in Parkinson's Disease Mice by Inhibiting HDAC2/MAPK Signaling and Reducing Microglia Polarization.

Parkinson's disease (PD) is a common neurodegenerative disorder caused by dopaminergic neuron progressive degeneration. Inhibition of microglial activation may contribute to the treatment and prevention of PD. Plantamajoside (PMS) is a natural compound extracted from plantain seeds. It has a wide range of biological activities, including anti-inflammatory, antioxidative, as well as antitumor effects. However, its possible effects on PD are still unclear. In this study, lipopolysaccharide (LPS) was first injected into the right midbrain substantia nigra (SN) of male C57BL/6 mice to establish the PD mouse model. We found that PMS improved LPS-induced behavioral dysfunction in PD mice. PMS attenuated LPS-induced SN injury in PD mice. PMS could suppress LPS-induced microglial overactivation in PD mice. In addition, MS inhibited LPS-induced activation of the HDAC2/MAPK pathway in PD mice and BV-2 cells. It further revealed that PMS alleviated microglia polarization by inhibiting HDAC2. The limitation of this study was the lack of experiments for investigating the further molecular mechanism and in vivo animal validation, which needs to be further confirmed in the future. Collectively, our data suggested that PMS could serve as a promising drug for PD.

How to improve the diagnosis of neoplastic transformation of gastric hyperplastic polyps in the context of autoimmune gastritis?: A case report and lierature review.

RATIONALE: Gastric hyperplastic polyp (GHP) commonly arises in the abnormal background mucosa, which makes it easy to be misdiagnosed and missed, and has a potential risk of malignant transformation over time. Here, we present a case of neoplastic transformation of GHP in a context of autoimmune gastritis (AIG). PATIENT CONCERNS: In 2020, a 67-year-old woman was admitted for endoscopic review 6 years after gastric polyp resection, the histological diagnosis of gastric polyp was neoplastic transformation of GHP as before. The patient had undergone multiple polypectomies at the same part. Then histological examination revealed that partial epithelial hyperplasia and dysplasia, and the neoplastic areas were interlaced with normal mucosa. DIAGNOSES AND INTERVENTIONS: We further found that the background diagnosis was AIG. These results supported the diagnosis of neoplastic transformation of GHP in a context of AIG. With the doubt of missed diagnose, we retrospectively analyzed the medical history in 2014, 2015 and 2016, confirmed the presence of AIG. Unfortunately, serological tests and special treatment were not performed. OUTCOMES: The correct diagnosis was eventually confirmed in 2020, which enables patients to receive normal treatment and monitoring, and avoids further deterioration of the disease. LESSONS: The purpose of this case report is to increase clinical awareness of neoplastic transformation of GHP in a context of AIG, and hope promise for early diagnosis and treatment.

Anti-inflammatory effects of ß-ionone-curcumin hybrid derivatives against ulcerative colitis.

A series of ß-ionone-curcumin hybrid derivatives were designed and chosen to merge the biological characteristics of two parent molecules and to obtain a leading compound with higher biological activity. Through the initial screening, the structure activity relationship of their hybrid derivatives as inhibitors of nitric oxide (NO) production showed that meta-substituted derivatives exhibited the best inhibitory activity, among which 1h was the best one. In lipopolysaccharide-induced Raw264.7 macrophage cells, 1h showed anti-inflammatory activity by inhibiting the productions of NO and reactive oxygen species, the expressions of Interleukin-1ß and tumor necrosis factor-α, and the translocation of nuclear factor (NF)-κB from the cytosol to the nucleus. Furthermore, molecular docking simulation displayed that 1h could interact with cluster of differentiation 14 to inhibit the toll-like receptor 4/NF-κB signaling. In dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) of mice, 100 mg/kg of 1h could significantly reduce the colon length shortening and protect against colon injury, liver injury and oxidative stress in DSS-induced UC of mice. Besides, 1h was safety in vivo. In conclusion, 1h was the potential anti-inflammatory agent, and further investigations were underway in our laboratory.

Evaluation of Hepatoprotective Effects of Piperlongumine Derivative PL 1-3-Loaded Albumin Nanoparticles on Lipopolysaccharide/d-Galactosamine-Induced Acute Liver Injury in Mice.

In recent years, piperlongumine (PL) having specific cytotoxicity has attracted considerable attention for anticancer activity. Through structural modification, the active derivative PL 1-3 shows potential anti-inflammatory activity and low cytotoxicity, but its water solubility is low. Here, PL 1-3-loaded bovine serum albumin nanoparticles (1-3 NPs) were prepared and characterized, which can improve the dissolution. 1-3 NPs exhibited effective hepatoprotective effects on lipopolysaccharide/d-galactosamine-induced acute liver injury of mice, which was similar to liver injury in clinical settings. 1-3 NPs treatment can inhibit inflammation, oxidative stress, and apoptosis via the downregulation of NF-κB signaling pathways, the activation of Nrf2/HO-1 signaling pathways, and the inhibition of expression of Bax and caspase 3 proteins. The above results demonstrated that PL 1-3-loaded bovine serum albumin nanoparticles possessed potential value in intervention of inflammation-based liver injury.

Speciation and bioaccessibility of arsenic in rice under different cooking methods and its implication in risk assessment.

Numerous studies have studied the health risk assessment of human exposure to As or bioaccessible As via rice intake; however, the bioaccessibility of different As species in rice is seldom reported. In the present study, 31 rice samples were collected from markets or individual growers to investigate the speciation and bioaccessibility of As. Five different species (AsIII, AsV, DMA, MMA, and AsB) were detected in rice samples from different regions, among which AsIII accounted for the largest proportion (62.95% in average), followed by DMA and AsV. In addition, the cooking method could facilitate the release of As from rice into gastric and intestinal juice, and subsequently increase the bioaccessibility of As. The bioaccessibility of inorganic As in cooked rice ranged from 71.83 to 100%, and that of organic As ranged from 31.69 to 61.04%. Non-carcinogenic and carcinogenic risk assessment of children and adults exposure to As via rice intake considering the bioaccessibility of cooked rice was carried out. The target hazard quotient (THQ) of iAs and total As for children ranged from 0.21 to 1.61 and 0.48 to 2.26, respectively, while those for adults ranged from 0.12 to 0.88 and 0.26 to 1.23, respectively. Incremental lifetime cancer risk (ILCR) for children and adults ranged from 9.57 [Formula: see text] 10-5 to 7.25 [Formula: see text] 10-4 and 5.21 [Formula: see text] 10-5 to 3.95 [Formula: see text] 10-4, respectively. The results of risk assessment indicated that children would face a higher health risk than adults when they took the same type of rice as their staple food.

Compound reutilization of waste cooking oil and waste engine oil as asphalt rejuvenator: performance evaluation and application.

The comprehensive utilization of waste cooking oil (WCO) and waste engine oil (WEO) is of great significance to build a sustainable society because recycling WCO and WEO to develop a rejuvenator for asphalt pavement not only aids the reduction of environmental pollution, but also brings about significant benefits to the Earth's sustainable development. With a clear aim to contribute to a more efficient reuse of the waste oils and recycled asphalt mixtures, this paper develops a high-efficiency compound rejuvenator and determines the optimal combination of its main constituents (WCO and WEO) through orthogonal tests. Furthermore, the performance of the rejuvenator is verified by means of the four-fraction test and the traditional asphalt performance tests (penetration, ductility, softening point). These tests confirm the regeneration efficiency of the compound rejuvenator, and the optimum dosage of the compound rejuvenator is found of 7%. Subsequently, the mechanism of the compound rejuvenator in aged asphalt is examined, and following the application of the compound rejuvenator, it was concluded that the reclaimed asphalt pavement (RAP) could be maximized by 45%. Consequentially, the results of this research promote the recycling of WEO, WCO, and waste asphalt pavement materials, ultimately advocating the sustainability of pavement construction.

A Prognostic Analysis of the Outcomes in Patients With Anti-γ-Aminobutyric Acid B Receptor Encephalitis.

Objective: To evaluate neurological function and its influencing factors in patients with anti-γ -aminobutyric acid B receptor (GABABR) encephalitis. Methods: This was a clinical cohort study of patients diagnosed with anti-GABABR encephalitis; long-term follow-up was performed by telephone. Clinical factors associated with prognosis were analyzed, including clinical manifestations, laboratory examinations, imaging features, tumor comorbidities and therapeutic responses. Results: Twenty-two patients with anti-GABABR encephalitis were evaluated (median age: 55 years). Lung cancer was detected in eight patients. All were with serum tumor markers (mainly NSE), and three of them had additional onconeuronal antibodies. The patients with tumors were older than the patients without tumors and more likely to develop status epilepticus (62.5% vs. 14.3%; p = 0.052), central hypoventilation (50% vs. 7.1%; p = 0.039), and hyponatremia (87.5% vs. 14.3%; p = 0.001). The patients with tumors had higher mortality (87.5% vs. 0%; p < 0.05). Although 92.9% of the patients without tumors became functionally independent (mRS ≤2), sequelae of symptomatic seizures, neuropsychiatric symptoms, and cognitive impairment were still observed in 14.3%, 21.4%, and 21.4% of patients, respectively. Conclusions: (1) Elderly patients with anti-GABABR antibodies, especially those with severe symptoms, serum tumor markers, and additional onconeuronal antibodies, should be screened for lung cancer. (2) Anti-GABABR encephalitis with tumors has a poor prognosis. (3) Most patients without tumors achieve self-care, but some still experience remaining neurological deficits.

SCU-Net: A deep learning method for segmentation and quantification of breast arterial calcifications on mammograms.

PURPOSE: Measurements of breast arterial calcifications (BAC) can offer a personalized, non-invasive approach to risk-stratify women for cardiovascular diseases such as heart attack and stroke. We aim to detect and segment breast arterial calcifications in mammograms accurately and suggest novel measurements to quantify detected BAC for future clinical applications. METHODS: To separate BAC in mammograms, we propose a lightweight fine vessel segmentation method Simple Context U-Net (SCU-Net). Due to the large image size of mammograms, we adopt a patch-based way to train SCU-Net and obtain the final whole-image-size results by stitching patchwise results together. To further quantify calcifications, we test five quantitative metrics to inspect the progression of BAC for subjects: sum of mask probability metric ( P M ), sum of mask area metric ( A M ), sum of mask intensity metric ( S I M ), sum of mask area with threshold intensity metric T A M X , and sum of mask intensity with threshold X metric T S I M X . Finally, we demonstrate the ability of the metrics to longitudinally measure calcifications in a group of 26 subjects and evaluate our quantification metrics compared with calcified voxels and calcium mass on breast CT for 10 subjects. RESULTS: Our segmentation results are compared with state-of-the-art network architectures based on recall, precision, accuracy, F1 score/Dice score, and Jaccard index evaluation metrics and achieve corresponding values of 0.789, 0.708, 0.997, 0.729, and 0.581 for whole-image-size results. The quantification results all show >95% correlation between quantification measures on predicted masks of SCU-Net as compared to the groundtruth and measurement of calcification on breast CT. For the calcification quantification measurement, our calcification volume (voxels) results yield R2 -correlation values of 0.834, 0.843, 0.832, 0.798, and 0.800 for the P M , A M , S I M , T A M 100 , T S I M 100 metrics, respectively; our calcium mass results yield comparable R2 -correlation values of 0.866, 0.873, 0.840, 0.774, and 0.798 for the same metrics. CONCLUSIONS: Simple Context U-Net is a simple method to accurately segment arterial calcification retrospectively on routine mammograms. Quantification of the calcifications based on this segmentation in the retrospective cohort study has sufficient sensitivity to detect the normal progression over time and should be useful for future research and clinical applications.

TilGAN: GAN for Facilitating Tumor-Infiltrating Lymphocyte Pathology Image Synthesis With Improved Image Classification.

Tumor-infiltrating lymphocytes (TILs) act as immune cells against cancer tissues. The manual assessment of TILs is usually erroneous, tedious, costly and subject to inter- and intraobserver variability. Machine learning approaches can solve these issues, but they require a large amount of labeled data for model training, which is expensive and not readily available. In this study, we present an efficient generative adversarial network, TilGAN, to generate high-quality synthetic pathology images followed by classification of TIL and non-TIL regions. Our proposed architecture is constructed with a generator network and a discriminator network. The novelty exists in the TilGAN architecture, loss functions, and evaluation techniques. Our TilGAN-generated images achieved a higher Inception score than the real images (2.90 vs. 2.32, respectively). They also achieved a lower kernel Inception distance (1.44) and a lower Fréchet Inception distance (0.312). It also passed the Turing test performed by experienced pathologists and clinicians. We further extended our evaluation studies and used almost one million synthetic data, generated by TilGAN, to train a classification model. Our proposed classification model achieved a 97.83% accuracy, a 97.37% F1-score, and a 97% area under the curve. Our extensive experiments and superior outcomes show the efficiency and effectiveness of our proposed TilGAN architecture. This architecture can also be used for other types of images for image synthesis.

Network Pharmacology Analysis of ZiShenWan for Diabetic Nephropathy and Experimental Verification of Its Anti-Inflammatory Mechanism.

BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). The inflammatory response plays a critical role in DN. ZiShenWan (ZSW) is a classical Chinese medicinal formula with remarkable clinical therapeutic effects on DN, but its pharmacological action mechanisms remain unclear. AIM: In this study, a network pharmacology approach was applied to investigate the pharmacological mechanisms of ZSW in DN therapy. Based on the results of network analysis, the core targets and signaling pathways related to anti-inflammatory effect were verified via experiments in vivo. METHODS: The candidate chemical ingredients of ZSW as well as its putative targets and known therapeutic targets of DN were acquired from appropriate databases. The "herb-ingredient-target" network for ZSW in DN treatment was established. The protein-protein interaction (PPI) network of potential targets was constructed to screen the core targets. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. In addition to biochemical and pathological indicators, the core targets and signaling pathways associated with inflammation were partially validated in db/db mice at molecular level. RESULTS: A total of 56 active ingredients in ZSW and 166 DN-related targets were selected from databases. A high proportion of core targets and top signaling pathways participate in inflammation. ZSW markedly alleviated renal injuries pathologically and regulated related biomarkers. In particular, ZSW significantly inhibited the exaggerated release of inflammatory cytokines such as interleukin (IL)-1ß, IL-6, tumor necrosis factor receptor (TNF)-ɑ, and monocyte chemotactic protein (MCP)-1 as well as regulating p38 mitogen-activated protein kinases (MAPK) and phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signaling pathways in db/db mice. CONCLUSION: This study first comprehensively investigated the active ingredients, potential targets, and molecular mechanism of ZSW as a therapy for DN. ZSW achieved renoprotective effects in DN via regulation of multiple targets and signaling pathways, especially by alleviating inflammation. Results indicate that ZSW is a promising multi-target therapeutic approach for DN treatment.

Polyphenol oxidase dominates the conversions of flavonol glycosides in tea leaves.

Flavonol glycosides are associated with astringency and bitterness of teas. To clarify the dominant enzymatic reaction of flavonol glycosides in tea leaves, the catalytic effects of polyphenol oxidase (PPO), peroxidase (POD) and ß-glucosidase were studied, with the maintaining rates of total flavonol glycosides (TFG) being 73.0%, 99.8% and 94.3%. PPO was selected for further investigations, including the effects of pH value (3.5 ~ 6.5), temperature (25 °C ~ 55 °C) and dosage (39 ~ 72 U/mL PPO and 36 U/mL PPO, 3 ~ 36 U/mL POD). The oxidation of flavonol glycosides were intensified at pH 6.5, with 51.8% and 15.4% of TFG maintained after PPO and PPO + POD treatments, suggesting an enhancement from POD. The sensitivity ranking to PPO was: myricetin glycosides > quercetin glycosides > kaempferol glycosides. The inhibitor treatment testified the leading role of PPO in catalyzing flavonol glycosides in tea leaves. Sugar moiety enhanced the docking affinity of flavonol glycosides for PPO. PPO shows the potential of modifying flavonol glycoside composition.

Effectiveness of Tolvaptan in the Treatment for Patients with Autosomal Dominant Polycystic Kidney Disease: A Meta-analysis.

AIMS AND OBJECTIVE: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common chronic kidney disease that leads to End-Stage Renal Disease (ESRD). The key target of this therapy is to prevent the progression of kidney failure. Tolvaptan could slow kidney cyst growth and are proven highly effective. The aims of this analysis are to perform a systematic review, estimate and evaluate the efficacy and safety of tolvaptan in ADPKD patients. MATERIALS AND METHODS: Randomized controlled trials of tolvaptan in ADPKD were identified in PubMed, Ovid, Web of Science and the Cochrane Library electronic database. The changes observed in kidney function, treatment efficiency and the incidence of adverse events between the tolvaptan and placebo groups were compared. Data were analyzed by the RevMan software. RESULTS: Eight trials, including 7 double-blinded randomised controlled trials and 1 quasi RCT involving 1,536 patients were extracted. Significant differences in the annual rate of change in the total kidney volume TKV at any stages of CKD (MD = -3.32, 95%CI =-4.57,-2.07, I2 =70%) and the glomerular filtration rate (MD = 1.4, 95%CI = 0.83,1.97, I2 =0%) were observed between the tolvaptan group and the placebo group. Subgroup analysis of patients in different CKD stages also showed the same conclusion. There was an increase in the urine osmolality, and 24-hour urine volume in patients receiving tolvaptan. Tolvaptan reduced the rate of serious hypertension and kidney pain events in ADPKD patients. At higher doses, it increased the rate of adverse events (liver injuries, thirst, pollakiuria, and nocturia). There was no significant risk of bias in the included studies. CONCLUSION: Tolvaptan has a beneficial effect on ADPKD, but is associated with an increase in adverse events at high doses when compared with the placebo. Further RCTs on tolvaptan may be required to support this conclusion.

Pep-1&borneol-Bifunctionalized Carmustine-Loaded Micelles Enhance Anti-Glioma Efficacy Through Tumor-Targeting and BBB-Penetrating.

Tumor-targeting and blood-brain barrier (BBB)-penetrating are highly desirable for the treatment of glioma. In this study, we developed Pep-1&borneol-bifunctionalized carmustine-loaded micelles (Pep-1/Bor/CMS-M) capable of targeting interleukin-13 receptor-overexpressed glioma and penetrating the brain microvascular endothelial cells-associated physiologic barriers. Pep-1/Bor/CMS-M were nearly spherical particles with a diameter of 32.6 ± 1.1 nm and zeta potential of -21.3 ± 3.1 mV. Carmustine (CMS) released from Pep-1/Bor/CMS-M in pH 7.4 was significantly faster than in acidic environments. In human glioma BT325 cellular studies, Pep-1/Bor/CMS-M remarkably increased the cytotoxicity, notably improved the internalization, and effectively induced the cell apoptosis. Likewise, in human brain microvascular endothelial cells, Pep-1/Bor/CMS-M obviously promoted the cellular uptake, rapidly decreased the transepithelial electrical resistance, and thereby enhanced the ability of penetration. In orthotopic Luc-BT325 glioma tumor-bearing nude mouse models, the stronger fluorescence signal and longer retention were observed in brain tissues compared with other controls, after single administration of DiD-labeled Pep-1/Bor/M (DiD/Pep-1/Bor/M). Importantly, Pep-1/Bor/CMS-M displayed the strongest inhibition of tumor growth, the longest survival period, and low systemic toxicity in treating orthotopic glioma tumor-bearing nude mice. Simultaneous functionalization of Pep-1 and borneol offers a novel strategy for designing CMS-based nanomedicine and precisely treating glioma.

Clumped Nuclei Segmentation with Adjacent Point Match and Local Shape-Based Intensity Analysis in Fluorescence Microscopy Images.

Highly clumped nuclei captured in fluorescence microscopy images are commonly observed in a wide spectrum of tissue-related biomedical investigations. To ensure the quality of downstream biomedical analyses, it is essential to accurately segment clustered nuclei. However, this presents a technical challenge as fluorescence intensity alone is often insufficient for recovering the true nuclei boundaries. In this paper, we propose an segmentation algorithm that identifies point pair connection candidates and evaluates adjacent point connections with a formulated ellipse fitting quality indicator. After connection relationships are determined, we recover the resulting dividing paths by following points with specific eigenvalues from the image Hessian in a constrained searching space. We validate our algorithm with 560 image patches from two classes of tumor regions of seven brain tumor patients. Both qualitative and quantitative experimental results suggest that our algorithm is promising for dividing overlapped nuclei in fluorescence microscopy images widely used in various biomedical research.

The Three Members of the Arabidopsis Glycosyltransferase Family 92 are Functional ß-1,4-Galactan Synthases.

Pectin is a major component of primary cell walls and performs a plethora of functions crucial for plant growth, development and plant-defense responses. Despite the importance of pectic polysaccharides their biosynthesis is poorly understood. Several genes have been implicated in pectin biosynthesis by mutant analysis, but biochemical activity has been shown for very few. We used reverse genetics and biochemical analysis to study members of Glycosyltransferase Family 92 (GT92) in Arabidopsis thaliana. Biochemical analysis gave detailed insight into the properties of GALS1 (Galactan synthase 1) and showed galactan synthase activity of GALS2 and GALS3. All proteins are responsible for adding galactose onto existing galactose residues attached to the rhamnogalacturonan-I (RG-I) backbone. Significant GALS activity was observed with galactopentaose as acceptor but longer acceptors are favored. Overexpression of the GALS proteins in Arabidopsis resulted in accumulation of unbranched ß-1, 4-galactan. Plants in which all three genes were inactivated had no detectable ß-1, 4-galactan, and surprisingly these plants exhibited no obvious developmental phenotypes under standard growth conditions. RG-I in the triple mutants retained branching indicating that the initial Gal substitutions on the RG-I backbone are added by enzymes different from GALS.

Neural Stem Cells Alleviate Inflammation via Neutralization of IFN-γ Negative Effect in Ischemic Stroke Model.

Inflammatory response generated by ischemic stroke commonly affects functional or structural recovery. The aim of this study was to examine the IFN-γ caused inflammatory effects on NSCs in vitro and in vivo. We found that IFN-γ did not affect NSCs proliferation but increased the SOD2 level of inflammatory oxidative stress in NSCs culturing. High dose IFN-γ (500 ng) injection aggravated the level of inflammation in the cerebral ischemic model but did not alter the repairing functions of the NSCs in vivo. NSCs based treatment, including the NSCs-IFN-γ combined treatment, significantly improved the ischemic microenvironment by decreasing CD4+, CD8+ T cells and microglia infiltration. Furthermore, anti-inflammatory cytokines IL-10 and TGF-ß1 expression were increased in the NSCs and combined treatment groups, but the level of pro-inflammatory cytokines (IL-1 ß, IL-6, IFN-γ, and TNF-α) were decreased. The IFN-γ/Stat1 signaling pathway was also activated. NSCs transplantation therefore promoted the neurological recovery of ischemic stroke rats mainly by altering the inflammatory microenvironment, neutralizing the negative effect of IFN-γ. In conclusion, in addition to promoting cell replacement or engraftment, the NSCs-based transplantation also enhanced the therapeutic effects of transplantation by optimizing its immune microenvironment of ischemic areas.