Zinc Deficiency Exacerbates Behavioral Impediments and Dopaminergic Neuron Degeneration in a Mouse Model of Parkinson Disease.

BACKGROUND: Circulating zinc (Zn) concentrations are lower than normal in patients with Parkinson disease (PD). It is unknown whether Zn deficiency increases the susceptibility to PD. OBJECTIVES: The study aimed to investigate the effect of dietary Zn deficiency on behaviors and dopaminergic neurons in a mouse model of PD and to explore potential mechanisms. METHODS: Male C57BL/6J mice aged 8-10 wk were fed Zn adequate (ZnA; 30 µg/g) or Zn deficient (ZnD; <5 µg/g) diet throughout the experiments. Six weeks later 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was injected to generate the PD model. Controls were injected with saline. Thus, 4 groups (Saline-ZnA, Saline-ZnD, MPTP-ZnA, and MPTP-ZnD) were formed. The experiment lasted 13 wk. Open field test, rotarod test, immunohistochemistry, and RNA sequencing were performed. Data were analyzed with t-test, 2-factor ANOVA, or Kruskal-Wallis test. RESULTS: Both MPTP and ZnD diet treatments led to a significant reduction in blood Zn concentrations (PMPTP = 0.012, PZn = 0.014), reduced total distance traveled (PMPTP < 0.001, PZn = 0.031), and affected the degeneration of dopaminergic neurons in the substantia nigra (PMPTP < 0.001, PZn = 0.020). In the MPTP-treated mice, the ZnD diet significantly reduced total distance traveled by 22.4% (P = 0.026), decreased latency to fall by 49.9% (P = 0.026), and reduced dopaminergic neurons by 59.3% (P = 0.002) compared with the ZnA diet. RNA sequencing analysis revealed a total of 301 differentially expressed genes (156 upregulated; 145 downregulated) in the substantia nigra of ZnD mice compared with ZnA mice. The genes were involved in a number of processes, including protein degradation, mitochondria integrity, and α-synuclein aggregation. CONCLUSIONS: Zn deficiency aggravates movement disorders in PD mice. Our results support previous clinical observations and suggest that appropriate Zn supplementation may be beneficial for PD.

LSD1-Demethylated LINC01134 Confers Oxaliplatin Resistance Through SP1-Induced p62 Transcription in HCC.

BACKGROUND AND AIMS: Oxaliplatin (OXA) is one of the most common chemotherapeutics in advanced hepatocellular carcinoma (HCC), the resistance of which poses a big challenge. Long noncoding RNAs (lncRNAs) play vital roles in chemoresistance. Therefore, elucidating the underlying mechanisms and identifying predictive lncRNAs for OXA resistance is needed urgently. METHODS: RNA sequencing (RNA-seq) and fluorescence in situ hybridization (FISH) were used to investigate the OXA-resistant (OXA-R) lncRNAs. Survival analysis was performed to determine the clinical significance of homo sapiens long intergenic non-protein-coding RNA 1134 (LINC01134) and p62 expression. Luciferase, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and chromatin isolation by RNA purification (ChIRP) assays were used to explore the mechanisms by which LINC01134 regulates p62 expression. The effects of LINC01134/SP1/p62 axis on OXA resistance were evaluated using cell viability, apoptosis, and mitochondrial function and morphology analysis. Xenografts were used to estimate the in vivo regulation of OXA resistance by LINC01134/SP1/p62 axis. ChIP, cell viability, and xenograft assays were used to identify the demethylase for LINC01134 up-regulation in OXA resistance. RESULTS: LINC01134 was identified as one of the most up-regulated lncRNAs in OXA-R cells. Higher LINC01134 expression predicted poorer OXA therapeutic efficacy. LINC01134 activates anti-oxidative pathway through p62 by recruiting transcription factor SP1 to the p62 promoter. The LINC01134/SP1/p62 axis regulates OXA resistance by altering cell viability, apoptosis, and mitochondrial homeostasis both in vitro and in vivo. Furthermore, the demethylase, lysine specific demethylase 1 (LSD1) was responsible for LINC01134 up-regulation in OXA-R cells. In patients with HCC, LINC01134 expression was positively correlated with p62 and LSD1 expressions, whereas SP1 expression positively correlated with p62 expression. CONCLUSIONS: LSD1/LINC01134/SP1/p62 axis is critical for OXA resistance in HCC. Evaluating LINC01134 expression in HCC will be effective in predicting OXA efficacy. In treatment-naive patients, targeting the LINC01134/SP1/p62 axis may be a promising strategy to overcome OXA chemoresistance.

FOXO3A-induced LINC00926 suppresses breast tumor growth and metastasis through inhibition of PGK1-mediated Warburg effect.

Phosphoglycerate kinase 1 (PGK1), a critical component of the glycolytic pathway, relates to the development of various cancers. However, the mechanisms of PGK1 inhibition and physiological significance of PGK1 inhibitors in cancer cells are unclear. Long non-coding RNAs (lncRNAs) play a vital role in tumor growth and progression. Here, we identify a lncRNA LINC00926 that negatively regulates PGK1 expression and predicts good clinical outcome of breast cancer. LINC00926 downregulates PGK1 expression through the enhancement of PGK1 ubiquitination mediated by E3 ligase STUB1. Moreover, hypoxia inhibits LINC00926 expression and activates PGK1 expression largely through FOXO3A. FOXO3A/LINC00926/PGK1 axis regulates breast cancer glycolysis, tumor growth, and lung metastasis both in vitro and in vivo. In breast cancer patients, LINC00926 expression is negatively correlated with PGK1 and positively correlated with FOXO3A expression. Our work established FOXO3A/LINC00926/PGK1 as a critical axis to regulate breast cancer growth and progression. Targeting PGK1 or supplement of LINC00926 or FOXO3A could be potential therapeutic strategies in breast cancer.

Pituitary metastasis from renal cell carcinoma: case report and review of the literature.

Pituitary metastasis(PM) from renal cell carcinoma(RCC) is rare, and is easy to be misdiagnosed. Here, we present a case of pituitary metastasis from clear-cell renal cell carcinoma(ccRCC) which was difficult to distinguish from other sellar region tumors. In addition, we systematically review the literature to find the characteristics of different tumors of the sellar region. It provides a new idea for the diagnosis of sellar region tumors in the clinic.

Glutamate dehydrogenase mediated amino acid metabolism after ammonium uptake enhances rice growth under aeration condition.

KEY MESSAGE: Aeration stimulates the rice growth and nitrogen (N) metabolism; in which, the glutamate accumulation limited by the glutamate dehydrogenase pathway after ammonia uptake may control root N metabolism during aeration. Increasing rhizosphere oxygen content greatly improves rice growth and biomass. To study the intrinsic mechanism involved in nitrogen (N) metabolism, a hydroponic experiment was conducted by supplying two different oxygen levels to two different rice genotypes. Compared to the hypoxia-resistant cultivar (Nip; japonica rice 'Nipponbare'), the hypoxia-sensitive cultivar (U502; upland rice 'Upland 502') presented with severe oxidative damage under the lack of aeration. However, aeration significantly reduced root oxidative damage by enhancing root antioxidant capacity and leaf photosynthesis especially in U502, and significantly increased nitrate (NO3-) and ammonia (NH4+) uptake and upregulated the expression of the genes controlling these processes. Additional NO3- was mainly incorporated into amino acids in the leaves whereas NH4+ assimilation occurred mostly in the roots. The 15N gas chromatography-mass spectrometry analysis demonstrated that aeration had no influence on the compositions of the individual amino acids derived from 15NO3- in the roots, but increased labeled glutamic acid (Glu), asparagine, γ-aminobutyric acid, and alanine in 15NH4+-treated roots. Aeration inhibited root glutamate synthetase activity but this did not inhibit 15N-Glu production from 15NH4+. In contrast, aeration upregulated isocitrate dehydrogenase and glutamate dehydrogenase. These mechanisms and soluble carbohydrates may constitute an alternative pathway for Glu production in which amino acid metabolism is enhanced after NH4+ uptake during aeration. Therefore, the rice growth-enhancing effect of aeration is closely correlated with root redox equilibrium, N uptake, and amino acid metabolism. Glutamic acid accumulation is limited by the glutamate dehydrogenase pathway after NH4+ uptake and may control root N metabolism during aeration.

A good choice for the patients with prior failed ventriculoperitoneal shunt treatment of suprasellar arachnoid cysts: endoscopic fenestration.

To investigate the effectiveness of endoscopic fenestration in the patients with prior failed ventriculoperitoneal (VP) shunt treatment of suprasellar arachnoid cysts (SACs). Between 2012 and 2018, four pediatric patients of SACs with previous failed VP shunt treatment were surgically treated using endoscopic ventriculocystocisternostomy (VCC) in our hospital. The clinical symptoms, imaging data, and surgical outcomes were collected and analyzed retrospectively. A literature review is provided with regard to the reasons of shunt failure and surgical outcome of further endoscopic fenestration in the previously reported patients of SACs with prior failed VP shunt. For the 4 cases, the initial clinical symptoms relieved or even disappeared after shunt placement, but, respectively, recurred 2, 6, 11, and 6 months later. MR scans were conducted when the clinical symptoms reappeared and showed a cyst had greatly enlarged after shunt placement. Furthermore, VP shunt-related slit ventricle was also demonstrated in 3 cases. Clinical improvement and cysts shrinkage occurred in all 4 patients after VCC. Slit ventricle and hydrocephalus were also resolved. Three patients had their shunt apparatus removed after VCC, and another patient's guardian refused to remove the shunt apparatus. Subdural hematoma occurred in one case after shunt apparatus removal. Four patients have been stable during follow-up period (mean follow-up 26.5 months). All the three patients whose VP shunt were removed were shunt independence. There were 24 patients who underwent endoscopic fenestration as an alternative to the failed VP shunt treatment in the published reports. Added our 4 patients to the published group, the effective rate of endoscopic fenestration for SACs following previous failed VP shunt treatment was approximately 93% (26/28). Of the 24 patients, the shunt apparatuses were in situ or reimplantation in 9 patients due to shunt dependence. The correction to recognize the SAC is the first condition to select the optimal management philosophy. The analysis of the series suggests endoscopic operation is still an effective and safe option in the SAC patients with previous failed VP shunt, and the shunt apparatus can be removed for some patients. The short interval time between shunt operation and endoscopic fenestration is conductive to return patients to the shunt-free state.

Variability of leaf photosynthetic characteristics in rice and its relationship with resistance to water stress under different nitrogen nutrition regimes.

The negative effects of water stress on rice can be alleviated by NH4 + nutrition. However, the effects of mixed nitrogen (N) nutrition (NO3 - + NH4 + ) on resistance to water stress are still not well known. To investigate the response of rice growth to water stress and its relationship with photosynthetic characteristics, a hydroponic experiment supplying different N forms was conducted. Compared with NO3 - nutrition, mixed-N and NH4 + nutrition greatly alleviated the reduction of leaf area, chlorophyll content, and photosynthesis under water stress, whilst subsequently maintaining higher biomass. In contrast, water stress inhibited the root-shoot ratios in NH4 + - and mixed-N-supplied plants, indicating reduced root growth and higher photosynthate availability to shoots. The following key observations were made: (1) a similar stomatal limitation and low proportion of activated Rubisco were observed among the three different N nutrition regimes; (2) increased mesophyll conductance in NH4 + - and mixed-N-supplied plants simultaneously stimulated leaf photosynthesis and improved the water use efficiency and (3), the maximum carboxylation rate and actual photochemical efficiency of photosystem II in NH4 + - and mixed-N-supplied plants were significantly higher than that in NO3 - -supplied plants, thus resulting in higher photochemical efficiency under water stress. In conclusion, mixed-N and NH4 + nutrition may be used to develop strategies for improved water stress resistance and stimulated biomass production under conditions of osmotic stress and possibly drought.

Multimaterial and multicolor 3D-printed model in training of transnasal endoscopic surgery for pituitary adenoma.

OBJECTIVE: The aim of the present study was to investigate the practical value of a multimaterial and multicolor 3D-printed model in anatomical teaching, surgical training, and preoperative planning of transnasal endoscopic surgery for pituitary adenoma. METHODS: Multimodality neuroimaging data were obtained in a 42-year-old healthy male volunteer and a 40-year-old female patient with an invasive nonfunctional pituitary adenoma. Three 3D-printed models were produced: a monomaterial and monocolor model, a monomaterial and multicolor model, and a multimaterial and multicolor model. The effects on anatomical teaching and surgical training for exposing the vidian nerve were assessed by 12 residents, and the training effect was validated on cadavers. The practical values for preoperative planning were evaluated by 6 experienced neurosurgeons. All evaluations were based on 5-point Likert questionnaires. RESULTS: The multimaterial and multicolor model was superior to the monomaterial models in surgical training for exposing the vidian nerve (Fisher test; p < 0.05). In addition, the multimaterial and multicolor model was superior to the monomaterial models in anatomical teaching and preoperative planning (Friedman test; p < 0.05). CONCLUSIONS: Multimaterial and multicolor 3D printing technology makes it convenient and efficient to produce a practical model for simulating individualized and complex anatomical structures in the sellar region. Furthermore, the multimaterial model can provide a more realistic manipulative experience for surgical training and facilitate the preoperative planning.

The Cytochrome P450 Enzyme Responsible for the Production of (Z)-Norendoxifen in vitro.

Norendoxifen, an active metabolite of tamoxifen, is a potent aromatase inhibitor. Little information is available regarding production of norendoxifen in vitro. Here, we conducted a series of kinetic and inhibition studies in human liver microsomes (HLMs) and expressed P450s to study the metabolic disposition of norendoxifen. To validate that norendoxifen was the metabolite of endoxifen, metabolites in HLMs incubates of endoxifen were measured using a HPLC/MS/MS method. To further probe the specific isoforms involved in the metabolic route, endoxifen was incubated with recombinant P450s (CYP 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4, 3A5 and CYP4A11). Formation rates of norendoxifen were evaluated in the absence and presence of P450 isoform specific inhibitors using HLMs. The peak of norendoxifen was found in the incubations consisting of endoxifen, HLMs, and cofactors. The retention times of norendoxifen, endoxifen, and the internal standard (diphenhydramine) were 7.81, 7.97, and 5.86 min, respectively. The Km (app) and Vmax (app) values of norendoxifen formation from endoxifen in HLM was 47.8 µm and 35.39 pmol min-1 mg-1 . The apparent hepatic intrinsic clearances of norendoxifen formation were 0.74 µl mg-1 min. CYP3A5 and CYP2D6 were the major enzymes capable of norendoxifen formation from endoxifen with the rates of 0.26 and 0.86 pmol pmol-1 P450 × min. CYP1A2, 3A2, 2C9, and 2C19 also contributed to norendoxifen formation, but the contributions were at least 6-fold lower. One micromolar ketoconazole (CYP3A inhibitor) showed an inhibitory effect on the rates of norendoxifen formation by 45%, but 1 µm quinidine (CYP2D6 inhibitor) does not show any inhibitory effect. Norendoxifen, metabolism from endoxifen by multiple P450s that including CYP3A5.

Repeatability and Reproducibility of Quantitative Assessment of the Retinal Microvasculature Using Optical Coherence Tomography Angiography Based on Optical Microangiography.

OBJECTIVE: The aim of this study was to determine the repeatability and reproducibility of optical coherence tomography angiography (OCTA) based on optical microangiography (OMAG) measurements of macular vessels in normal eyes. METHODS: In this prospective cohort study, 40 eyes of 40 healthy volunteers underwent repeated OCTA (Cirrus HD-OCT 5000 angiography system, Carl Zeiss Meditec, Inc.) scans on two separate visit days. On each visit day, the eyes were scanned three times. The following parameters were used to quantitatively describe the OCTA images of the superficial vascular network: vessel area density (VAD), vessel skeleton density (VSD), vessel diameter index (VDI), vessel perimeter index (VPI), vessel complexity index (VCI), flux, and foveal avascular zone (FAZ). Coefficient of variation (CV) and intraclass correlation coefficient (ICC) were calculated for evaluating intravisit and intervisit repeatability, as well as interobserver reproducibility. RESULTS: The measurements showed high repeatability [CVs ⪕ 4.2% (intravisit) and ⪕ 4.6% (intervisit)] and interobserver reproducibility (ICCs ⪖ 0.923) for all parameters. CONCLUSION: This study demonstrated good repeatability and reproducibility of OCTA based on OMAG for the measurement of superficial vessel parameters in normal eyes.

Effect of Microwave Vacuum Drying on the Drying Characteristics, Color, Microstructure, and Antioxidant Activity of Green Coffee Beans.

The aim of this study is to investigate the effect of microwave vacuum drying (MVD) on the drying characteristics and quality attributes of green coffee beans. We specifically focused on the effective moisture diffusion coefficient (Deff), surface temperature, glass transition temperature (Tg), water state, and microstructure. The kinetics of color changes during drying, total phenolic content (TPC), and antioxidant activity (DPPH, FRAP, and ABTS) were also characterized. Microwave power during MVD affected the porosity of coffee beans, their color, TPC, and antioxidant activity. The Allometric 1 model was the most suitable for simulating surface temperature rise kinetics. Thermal processing of green coffee beans resulted in increased b*, L*, ΔE, and TPC values, and greater antioxidant capacity. These findings may provide a theoretical reference for the technical improvement, mechanisms of flavor compound formation, and quality control of dried green coffee beans.

Bmi1 combines with oncogenic KRAS to induce malignant transformation of human pancreatic duct cells in vitro.

It is critical to understand the pathogenesis of preinvasive stages of pancreatic duct adenocarcinoma (PDAC) for developing novel potential diagnostic and therapeutic targets. The polycomb group family member B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi1) is overexpressed and involved in cancer progression in PDAC; however, its role in the multistep malignant transformation of human pancreatic duct cells has not been directly demonstrated. In this study, we stably expressed Bmi1 in a model of telomerase-immortalized human pancreatic duct-derived cells (HPNE) and showed that Bmi1 promoted HPNE cell proliferation, migration, and invasion but not malignant transformation. We then used mutant KRASG12D as a second oncogene to transform HPNE cells and showed that it further enhanced Bmi1-induced malignant potential. More importantly, coexpression of KRASG12D and Bmi1 caused anchorage-independent growth transformation in vitro but still failed to produce tumors in nude mice. Finally, we found that mutant KRASG12D induced HPNE-Bmi1 cells to undergo partial epithelial-mesenchymal transition (EMT) likely via upregulation of snail. Knockdown of KRASG12D significantly reduced the expression of snail and vimentin at both the messenger RNA (mRNA) and protein level and further impaired the anchorage-independent growth capability of invasive cells. In summary, our findings demonstrate that coexpression of Bmi1 and KRASG12D could lead to transformation of HPNE cells in vitro and suggest potential new targets for diagnosis and treatment of PDAC.

Anomalous left coronary artery arising from the pulmonary artery discovered beyond infancy.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a congenital heart defect rarely diagnosed beyond infancy. We present a 9-year-old girl who had once been diagnosed as congenital coronary artery fistula. Echogenic mitral chordae tendineae, multiple coronary collaterals within the ventricular septum and free ventricular wall, and a shunting flow from the left coronary artery into the pulmonary artery were prominent echocardiographic features of ALCAPA. Reimplantation of the left coronary artery directly onto the aorta achieved a favorable outcome with regression of left ventricular size and alleviation of mitral regurgitation.

[Determination of five components in rongxin pills by HPLC].

To establish a method for determination contents of schizandrin, tanshinone I, cryptotanshinone, tanshinone II (A) and schizandrin B in rongxin pills. The HPLC method was performed on an Agilent C18. The mobile phase was composed of methnol and water wish gradient elution. The flow rate was 1.0 mL x min(-1). The column temperature was 30 degrees C and the detection wavelength wash 240 nm. The linear of schizandrin, tanshinone I, cryptotanshinone, Tanshinone II (A) and schizandrin B were 3.000-48.00 (r = 1.000), 3.985-63.76 (r = 0.999 9), 6.370-101.9 (r = 1.000), 8.690-139.0 (r = 0.999 9), 1.700-27.20 mg x L(-1) (r = 0.999 9), respectively. The average recoveries were 98.44%, 100.3%, 99.29%, 99.07%, 98.42%, and RSDs were 0.61%, 1.1%, 0.52%, 0.72%, 0.97%. The method is convenient, accurate and has good precision. It can be used for determination of the preparation.

Microbiome-Metabolomic Analysis Revealed the Immunoprotective Effects of the Extract of Vanilla planifolia Andrew (EVPA) on Immunosuppressed Mice.

This study investigated the immunoprotective effects of the extract of Vanilla planifolia Andrew (EVPA) on cyclophosphamide (Cy)-induced immunosuppression in mice. The results show that EVPA administration significantly alleviated the immune damage induced by Cy, as evidenced by an improved body weight, organ index, and colonic injury. A further analysis of microbial diversity revealed that the EVPA primarily increased the abundance of the beneficial bacteria Verrucomicrobiota, Lactobacillaceae, and Lactobacillus while decreasing Akkermansiaceae, Akkermansia, Romboutsia, and Lactococcus, thereby ameliorating the microbial dysbiosis caused by Cy. A metabolomic analysis revealed significant alterations in the microbial metabolite levels after EVPA treatment, including urobilinogen, formamidopyrimidine nucleoside triphosphate, Cer (d18:1/18:0), pantetheine, and LysoPC (15:0/0:0). These altered metabolites are associated with pathways related to sphingolipid metabolism, carbapenem biosynthesis, pantothenate and CoA biosynthesis, glycerophospholipid metabolism, and porphyrin metabolism. Furthermore, significant correlations were observed between certain microbial groups and the differential metabolites. These findings provide new insights into the immunomodulatory effects of EVPA on the intestinal microbiota and metabolism, laying the foundation for more extensive utilization.

A rabbit model to study regression of ventricular hypertrophy.

BACKGROUND: The purpose of this study is to develop and characterise a reproducible rabbit model of LVH regression following pressure-induced myocardial hypertrophy. MATERIALS AND METHODS: Without endotracheal intubation and mechanical ventilation, a median sternotomy was performed. The median incision was made exactly along the midline of the sternum. Ascending aortic diameter was reduced 50% above the aortic valve, which lead to an approximate 75% reduction in crosssectional area. The sham-operated rabbits underwent the same procedures without actual ligation of the aorta. The animals of early DB group and late DB group were subjected to the second operation for removing the ligation eight weeks or 16 weeks after the initial banding surgery, respectively. Echocardiography, haemodynamic assessment, histology, and electron microscopy were used to assess functional and structural aspects of myocardial hypertrophy at each time point. RESULTS: The pressure overload resulted in robust LVH assessed by echocardiography, haemodynamic assessment, LV weight/body weight ratios, histology, and electron microscopy. Ascending aortic debanding completely or partially reversed LVH. The degree of LVH regression was association with the duration of pressure overload, proved by the fact that restoration of LV structure and function was complete in animals subjected to eight weeks of aortic banding but incomplete in animals subjected to 16 weeks of aortic banding. The animals did not experience severe mechanical ventilatory impairment. CONCLUSIONS: These results demonstrate an efficient and reproducible method of promoting LVH regression in rabbits without endotracheal intubation and mechanical ventilation.

[Comparison of green coffee beans volatiles chemical composition of Hainan main area].

Chemical component of Hainan green coffee beans was analyzed with solid phase microextraction-gas chromatography-mass spectrometry, and the discrepancy between two green coffee beans was differentiated through the spectrum database retrieval and retention index of compound characterization. The experimental results show that: the chemical composition of Wanning coffee beans and Chengmai coffee beans is basically the same. The quantity of analyzed compound in Wanning area coffee is 91, and in Chengmai area coffee is 106, the quantity of the same compound is 66, and the percent of the same component is 75.52%. The same compounds accounted for 89.86% of the total content of Wanning area coffee, and accounted for 85.70% of the total content of Chengmai area coffee.

Identification of fibroblast-related genes based on single-cell and machine learning to predict the prognosis and endocrine metabolism of pancreatic cancer.

Background: Single-cell sequencing technology has become an indispensable tool in tumor mechanism and heterogeneity studies. Pancreatic adenocarcinoma (PAAD) lacks early specific symptoms, and comprehensive bioinformatics analysis for PAAD contributes to the developmental mechanisms. Methods: We performed dimensionality reduction analysis on the single-cell sequencing data GSE165399 of PAAD to obtain the specific cell clusters. We then obtained cell cluster-associated gene modules by weighted co-expression network analysis and identified tumorigenesis-associated cell clusters and gene modules in PAAD by trajectory analysis. Tumor-associated genes of PAAD were intersected with cell cluster marker genes and within the signature module to obtain genes associated with PAAD occurrence to construct a prognostic risk assessment tool by the COX model. The performance of the model was assessed by the Kaplan-Meier (K-M) curve and the receiver operating characteristic (ROC) curve. The score of endocrine pathways was assessed by ssGSEA analysis. Results: The PAAD single-cell dataset GSE165399 was filtered and downscaled, and finally, 17 cell subgroups were filtered and 17 cell clusters were labeled. WGCNA analysis revealed that the brown module was most associated with tumorigenesis. Among them, the brown module was significantly associated with C11 and C14 cell clusters. C11 and C14 cell clusters belonged to fibroblast and circulating fetal cells, respectively, and trajectory analysis showed low heterogeneity for fibroblast and extremely high heterogeneity for circulating fetal cells. Next, through differential analysis, we found that genes within the C11 cluster were highly associated with tumorigenesis. Finally, we constructed the RiskScore system, and K-M curves and ROC curves revealed that RiskScore possessed objective clinical prognostic potential and demonstrated consistent robustness in multiple datasets. The low-risk group presented a higher endocrine metabolism and lower immune infiltrate state. Conclusion: We identified prognostic models consisting of APOL1, BHLHE40, CLMP, GNG12, LOX, LY6E, MYL12B, RND3, SOX4, and RiskScore showed promising clinical value. RiskScore possibly carries a credible clinical prognostic potential for PAAD.

Endoscopic Fenestration for Treating Galassi Type III Middle Cranial Fossa Arachnoid Cysts: Single- and Multiple-stoma have the Same Curative Effect.

BACKGROUND: For endoscopic fenestration of middle cranial fossa arachnoid cysts (MCFACs), the decisions on the location and number of stomas are key issues. However, research on this particular topic has been limited. Thus, this study aimed to compare single- versus multiple-stoma endoscopic fenestration for treating Galassi type III MCFACs. METHODS: This retrospective study included 86 patients with Galassi type III MCFACs treated with endoscopic fenestration. Single-stoma fenestration to the basal cistern was performed in 37 cases, whereas multiple-stoma fenestration to the basal cistern and the carotid cistern was performed in 49 cases. Clinicoradiologic profiles and follow-up data were analyzed. RESULTS: The rate of symptom relief was 83.7% (72/86), and the rate of cyst shrinkage was 96.5% (83/86). Postoperative ipsilateral subdural effusion, which was significant (p = 0.042), and noninfectious fever were the two most common complications in the single- and multiple-stoma groups. No significant differences in intraoperative nerve injury, vascular injury, proportion of cases with cyst reduction, and symptom remission rate were observed between the two groups. The rates of cyst recurrence and secondary surgery in the single-stoma group were higher than those in the multiple-stoma group, although the difference was not significant. CONCLUSION: Endoscopic fenestration is an effective and minimally invasive approach for treating Galassi type III MCFACs. Single- and multiple-stoma endoscopic fenestrations have the same curative effect.

Optimization of enzymatic process for vanillin extraction using response surface methodology.

Vanillin was extracted from vanilla beans using pretreatment with cellulase to produce enzymatic hydrolysis, and response surface methodology (RSM) was applied to optimize the processing parameters of this extraction. The effects of heating time, enzyme quantity and temperature on enzymatic extraction of vanillin were evaluated. Extraction yield (mg/g) was used as the response value. The results revealed that the increase in heating time and the increase in enzyme quantity (within certain ranges) were associated with an enhancement of extraction yield, and that the optimal conditions for vanillin extraction were: Heating time 6 h, temperature 60 °C and enzyme quantity 33.5 mL. Calculated from the final polynomial functions, the optimal response of vanillin extraction yield was 7.62 mg/g. The predicted results for optimal reaction conditions were in good agreement with experimental values.