Coupling capillary electrophoresis with mass spectrometry for the analysis of oxidized phospholipids in human high-density lipoproteins.

The oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (ox-PAPC) products in human high-density lipoproteins (HDLs) were investigated by low-flow capillary electrophoresis-mass spectrometry (low-flow CE-MS). To accelerate the optimization, native PAPC (n-PAPC) standard was first analyzed by a commercial CE instrument with a photodiode array detector. The optimal separation buffer contained 60% (v/v) acetonitrile, 40% (v/v) methanol, 20 mM ammonium acetate, 0.5% (v/v) formic acid, and 0.1% (v/v) water. The selected separation voltage and capillary temperature were 20 kV and 23°C. The optimal CE separation buffer was then used for the low-flow CE-MS analysis. The selected MS conditions contained heated capillary temperature (250°C), capillary voltage (10 V), and injection time (1 s). No sheath gas was used for MS. The linear range for n-PAPC was 2.5-100.0 µg/mL. The coefficient of determination (R2 ) was 0.9918. The concentration limit of detection was 1.52 µg/mL, and the concentration limit of quantitation was 4.60 µg/mL. The optimal low-flow CE-MS method showed good repeatability and sensitivity. The ox-PAPC products in human HDLs were determined based on the in vitro ox-PAPC products of n-PAPC standard. Twenty-one ox-PAPC products have been analyzed in human HDLs. Uremic patients showed significantly higher levels of 15 ox-PAPC products than healthy subjects.

Ent-labdane-type diterpene glycosides obtained from Rubus chingii Hu and their inhibitory effects on PDE5A activity.

In this study, 16 new ent-labdane-type diterpene glycosides, designated as goshonosides J1-J16 (1-16), along with nine previously known diterpene glycosides (17-25) were extracted from the fruits of Rubus chingii Hu. The structures of goshonosides J1-J16 were elucidated using various analytical techniques, such as nuclear magnetic resonance, electron capture detector ECD, high-resolution electrospray ionization mass spectrometry HREIMS, single-crystal X-ray diffraction, and hydrolysis. Furthermore, the isolates' efficacy in inhibiting the activity of phosphodiesterase type 5 A was evaluated. Goshonosides J1, J2, and G effectively inhibited the activity of the aforementioned enzyme (IC50 values: 6.15 ± 1.76, 3.27 ± 0.65, and 9.61 ± 2.36 µM, respectively). Our findings highlight the remarkable structural diversity of bioactive compounds in R. chingii Hu and offer insights into the use of this shrub.

Screw Pullout Strength After Pedicle Screw Reposition: A Finite Element Analysis.

RESEARCH DESIGN: Finite element analysis based on computed tomography images from the lumbar spine. OBJECTIVE: Determined the pullout strength of unsatisfactorily placed screws and repositioned screws after unsatisfactory place in lumbar spine surgery. BACKGROUND: Pedicle screws are widely used to stabilize the spinal vertebral body. Unsatisfactory screws could lead to surgical complications, and may need to be repositioned. Screw removal and reposition, however, may decrease pullout strength. METHODS: We conducted a three-dimensional finite element analysis based on high-resolution computed tomography images from a 39-year-old healthy woman. Pullout strength was determined with the screw placed in different orientations at the same entry point (as selected by the Magerl method), as well as after removal and reposition. The material properties of the vertebral body and the screw were simulated by using grayscale values and verified data, respectively. A load along the screw axis was applied to the end of the screw to simulate the pullout. RESULTS: The pullout strength was 1840.0 N with the Magerl method. For unsatisfactorily placed screws, the pullout strength was 1500.8 N at 20% overlap, 1609.6 N at 40% overlap, 1628.9 N at 60% overlap, and 1734.7 N at 80% overlap with the hypothetical screw path of the Magerl method. For repositioned screws, the pullout strength was 1763.6 N, with 20% overlap, 1728.3 N at 40% overlap, 1544.0 N at 60% overlap, and 1491.1 N at 80% overlap, with the original path. Comparison of repositioned screw with unsatisfactorily placed screw showed 14.04% decrease in pullout strength at 80% overlap, 5.21% decrease at 60% overlap, 7.37% increase at 40% overlap, and 17.51% increase at 20% overlap, with the screw path of the Magerl method. CONCLUSIONS: Removal and reposition increased the pullout strength at 20% and 40% overlap, but decreased the pullout strength at 60% and 80% overlap. For clinical translation, we recommend removal and reposition of the screw when the overlap is in the range of 20% to 40% or less. In vitro specimen studies are needed to verify these preliminary findings.

Comprehensive analysis of senescence-related genes and immune infiltration in intervertebral disc degeneration: a meta-data approach utilizing bulk and single-cell RNA sequencing data.

Objectives: This study aims to identify the key senescence genes and potential regulatory mechanisms that contribute to the etiology of intervertebral disc degeneration (IDD). Method: We analyzed GSE34095 and GSE70362 datasets, identifying key senescence-related differentially expressed genes (DEGs) in IDD using lasso regression. Risk scores classified patients into high- and low-risk groups. We compared pathways, functions, and immune infiltration between these groups. Diagnostic ability was assessed using ROC curves and a nomogram predicted IDD incidence. In single-cell dataset GSE165722, we evaluated expression of key senescence-related DEGs. Results: We identified 12 key senescence-related DEGs distinguishing high- and low-risk IDD patients. Enrichment analysis revealed cellular stress response, apoptotic signaling pathway, and protein kinase activation differences. Immune cell analysis showed elevated eosinophils in low-risk group and increased effector memory CD8 T, central memory CD4 T, myeloid-derived suppressor, natural killer, monocyte, Type 1 T helper, plasmacytoid dendritic, and natural killer T cells in high-risk group. A nomogram using AUC >0.75 genes (CXCL8, MAP4K4, MINK1, and TNIK) predicted IDD incidence with good diagnostic power. High senescence scores were observed in neutrophils. Conclusion: Our diagnostic model, based on key senescence-related DEGs and immune cell infiltration, offers new insights into IDD pathogenesis and immunotherapy strategies.

[Identification of Bacterial Flora and Metabolic Function of Sediments in Different Channels of Duliujian River Basin, Tianjin].

Bacterial communities are highly sensitive to environmental changes, but their metabolic functions may be convergent under similar ecological conditions. In order to test this environmental attribute of the bacterial community and verify the feasibility in using the bacterial metabolic data to divide functional units at the river basin scale, the surface sediments in three continuous spatial units of the main stream (MS), left tributary (LT), and right tributary (RT) of the Duliujian River basin were selected as the research objects. Therefore, 16S rDNA high-throughput sequencing and the PICRUSt platform were used to analyze the bacterial diversity and metabolic function of sediments in different units. The results showed that there were no significant differences for the Shannon and Simpson indices between the different river channels (P>0.05); however, the bacterial diversity indices of Chao1, ACE, Observed_species, and PD_whole_tree of LT and RT were significantly higher than those of the MS (P<0.05). Moreover, the dominant bacterial phyla were not significantly different among the different river channels. In the present study, a total of 41 metabolic pathways were predicted based on the KEGG database, among which 34 metabolic pathways such as membrane transport, amino acid metabolism, and carbohydrate metabolism were significantly different. The functional metabolic abundance was higher in MS than that in RT and LT (P<0.05); however, there was no significant difference between those of RT and LT (P>0.05). Except for exchangeable phosphorus and nitrate nitrogen, there were no significant differences in other physicochemical properties among the different river channels (P>0.05). Furthermore, pH and iron/aluminum-phosphorus were found to significantly affect the bacterial structure, and SOM and TN were found to significantly affect the bacterial metabolic function. Overall, the sediments of MS and tributaries (LT and RT) of the river were clearly divided into level-1 and level-2 groups, indicating that the metabolic abundance of the bacterial community can be used as the key indicator in the division of functional units at the river basin scale. This study provided a theoretical basis and technical support for ecological functional division and management in coastal river basins.

The Trans-Superior Articular Process Approach Utilizing Visual Trephine: A More Time-Saving and Effective Percutaneous Endoscopic Transforaminal Lumbar Discectomy for Migrated Lumbar Disc Herniation.

AIM: To introduce, and to evaluate the efficacy of the trans-superior articular process (trans-SAP) approach utilizing visual trephine in percutaneous endoscopic transforaminal lumbar discectomy (PETLD) for migrated lumbar disc herniation. MATERIAL AND METHODS: This study included 98 patients, 50 patients were in trans-SAP PETLD group and 48 patients were in conventional PETLD group. Visual analogue scale (VAS), Oswestry disability index (ODI), gender, age, blood loss, operation time, the frequency of X-ray fluoroscopy and the percentage of highly migrated herniation were evaluated and compared between the trans-SAP PETLD and conventional PETLD group. RESULTS: In both trans-SAP PETLD and conventional PETLD group, VAS and ODI were decreased at postoperative 1 day and 3 months compared with preoperative (p < 0.001). What's more, the VAS and ODI of postoperative 3 months were lower than postoperative 1 day (p < 0.001). There was no difference in gender, age, blood loss after the operation, and VAS during operation between trans-SAP group and conventional group (p > 0.05). The blood loss during the operation of trans-SAP group was higher (p < 0.05), but the operation time and frequency of X-ray fluoroscopy were lower than conventional group (p < 0.001). Last, trans-SAP group had a higher percentage of highly migrated herniation (p < 0.001). CONCLUSION: Both the conventional way and trans-SAP approach can achieve excellent surgical results. But, in trans-SAP group, the operation time is shorter, and X-ray fluoroscopy is less. PETLD with visual trephine has more advantages in highly migrated herniation and maybe easier to be mastered by young surgeons.

Effects of smartphone-based interventions and monitoring on bipolar disorder: A systematic review and meta-analysis.

BACKGROUND: Recently, there has been a range of studies about smartphone-based interventions and monitoring for reducing symptoms of bipolar disorder (BD). However, their efficacy for BD remains unclear. AIM: To compare the effect of smartphone-based interventions and monitoring with control methods in treating patients with BD. METHODS: A systematic literature search was performed on PubMed, Embase, Clinical trials, psycINFO, Web of Science, and Cochrane Library. Randomized clinical trials (RCTs) or single-group trials in which smartphone-based interventions and monitoring were compared with control methods or baseline in patients with symptoms of BD were included. Data were synthesized using a random-effects or a fixed-effects model to analyze the effects of psychological interventions and monitoring delivered via smartphone on psychiatric symptoms in patients with BD. The primary outcome measures were set for mania and depression symptoms. Subgroups were created to explore which aspects of smartphone interventions are relevant to the greater or lesser efficacy of treating symptoms. RESULTS: We identified ten articles, including seven RCTs (985 participants) and three single-group trials (169 participants). Analysis of the between-group study showed that smartphone-based interventions were effective in reducing manic [g = -0.19, 95% confidence interval (CI): -0.33 to -0.04, P = 0.01] and depressive (g = -0.28, 95%CI: -0.55 to -0.01, P < 0.05) symptoms. In within-group analysis, smartphone-based interventions significantly reduced manic (g = 0.17, 95%CI: 0.04 to 0.30, P < 0.01) and depressive (g = 0.48, 95%CI: 0.18 to 0.78) symptoms compared to the baseline. Nevertheless, smartphone-based monitoring systems significantly reduced manic (g = 0.27, 95%CI: 0.02 to 0.51, P < 0.05) but not depressive symptoms. Subgroup analysis indicated that the interventions with psychoeducation had positive effects on depressive (g = -0.62, 95%CI: -0.81 to -0.43, P < 0.01) and manic (g = -0.24, 95%CI: -0.43 to -0.06, P = 0.01) symptoms compared to the controlled conditions, while the interventions without psychoeducation did not (P > 0.05). The contacts between therapists and patients that contributed to the implementation of psychological therapy reduced depression symptoms (g = -0.47, 95%CI: -0.75 to -0.18, P = 0.01). CONCLUSION: Smartphone-based interventions and monitoring have a significant positive impact on depressive and manic symptoms of BD patients in between-group and within-group analysis.

A composite of graphene oxide and iron oxide nanoparticles for targeted drug delivery of temozolomide.

A magnetic targeting nanoparticle based on graphene oxide-ferroferric oxide (GO-Fe3O4) was investigated as a potential drug delivery vehicle. The formation of GO/Fe3O4 hybrid material was confirmed by Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy and transmission electron microscopy. The GO/Fe3O4 hybrid still shows a higher saturation magnetization of 58.42 emu/g after coating with graphene oxide. Drug loading and releasing experiments demonstrate the GO-Fe3O4 hybrid has a good loading capacity of (6.47±0.08) mg/mg for temozolomide and a satisfactory release under slightly acidic condition. The MTT assays of glioma C6 cells exhibits the GO-Fe3O4 hybrid does not display toxicity with the concentration ranged from 40 to 120 µg/mL in vitro, while the complex of temozolomide loaded on GO/Fe3O4 has a better inhibitory effect on the proliferation of rat glioma C6 cells. All results suggest the prepared GO/Fe3O4 has potential applications in targeted anticancer drug delivery.

Folate-modified Graphene Oxide as the Drug Delivery System to Load Temozolomide.

OBJECTIVE: The folate-modified graphene oxide (GO-FA), which had good stability and biocompatibility on rat glioma cells was successfully prepared. METHODS: The formation and composition of GO-FA were confirmed by Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM), Fourier Transform Infrared Spectrum (FT-IR), Raman spectra and X-ray Photoelectron Spectroscopy (XPS spectra). The cell experiment suggested good biocompatibility of GO-FA on rat glioma cells. RESULTS: The experiment of GO-FA loading with Temozolomide (TMZ) showed that the maximum drug loading of GO-FA was 8.05 ± 0.20 mg/mg, with the drug loading rate of 89.52 ± 0.19 %. When TMZ was released from the folate-modified graphene oxide loading with temozolomide (GO-FATMZ), its release behavior in vitro showed strong pH dependence and sustained release property. The growth of rat glioma cells can be effectively inhibited by GO-FA-TMZ, with the cell inhibition rate as high as 91.72 ± 0.13 % at the concentration of 600 µg/mL and time of 72 h. CONCLUSION: According to the above experimental results, this composite carrier has potential applications in drug delivery and cancer therapy.

[PM2.5 Pollution Characteristics During Winter and Summer in the Hohhot-Baotou-Ordos Region, China].

Based on the source apportionment by positive matrix factorization (PMF) model, we analyze the main sources and characteristics of aerosol fine particulate matter (PM2.5) during winter and summer in the Hohhot-Baotou-Ordos region, China. We found that organic (19.9%-44.6%) and crustal compositions (9.7%-46.2%) accounted for a large proportion of aerosol PM2.5 according to the results of mass closure. The results of source apportionment showed that the contribution of sources rank as:secondary inorganic aerosol (26.7%) > coal (26.1%) > motor vehicle (19.1%) > dust (18.1%) during winter, and as:secondary inorganic aerosol (26.7%) > dust (22.3%) > coal (16.6%) > vehicle exhaust (15.1%) > SOC (8.7%) during summer. Findings suggest that the contribution of sources with secondary inorganic aerosol were the largest sources both in winter and summer, and that the Hohhot-Baotou-Ordos region was also affected by coal during the winter and dust during the summer. Corresponding to the source apportionment, analysis of typical heavy pollution episodes in winter and summer showed that the pollution sources during the winter were mainly secondary inorganic aerosol and coal, whereas they were mainly secondary inorganic aerosol during the summer.

Noble gas insertion compounds of hydrogenated and lithiated hyperhalogens.

Based on density functional theory (DFT) calculations, hydrogenated hyperhalogen HM(BO2)2, lithiated hyperhalogen LiM(BO2)2 (M = Cu, Ag, Au), and their compounds with xenon were studied. Different insertion sites of Xe resulted in various isomers. According to the natural population analysis, the Xe atom donated 0.12-0.77 electrons to HM(BO2)2 and 0.14-0.41 electrons to LiM(BO2)2 when they combined, leading to metastable charge-transfer compounds in most cases. The nature of bonding between xenon and HM(BO2)2/LiM(BO2)2 was found to be related to its location. Covalent bonds were formed when Xe bound with hydrogen atoms, as indicated by the large Wiberg bond indices of the Xe-H bonds. The same was true for most Xe-M bondings. When an Xe-O connection was formed, it was either an ionic or van der Waals force in nature depending on the specific structural feature of the isomer. A parallel study on hyperhalogen-supported Ar and Kr compounds indicated that they were not very stable and were less likely to exist at room temperature, which was in accordance with the high inertness of both Ar and Kr atoms.

What Is the Appropriate Acupuncture Treatment Schedule for Chronic Pain? Review and Analysis of Randomized Controlled Trials.

BACKGROUND: Acupuncture is widely used for the treatment of chronic pain. Different protocols of acupuncture practice exist and lack agreement on the optimal schedule of acupuncture treatment. OBJECTIVE: To review the appropriate acupuncture treatment schedule for chronic pain. METHODS: Embase, Pubmed, Cochrane Central Register of Controlled Trials, and reference lists were searched from 2009 to 2018 to identify randomized controlled trials of acupuncture for chronic pain conditions. We collected factors of treatment schedule (D, duration of each treatment session; N, number of treatment sessions; T, total duration of treatment in weeks) from each of the trials, and the linear regression analysis with real pain relief rate (both treatment and follow-up) was performed. Furthermore, we recommend the concept of "DOSE" and frequency (F) to evaluate the dose and frequency effect of acupuncture. RESULTS: Twenty-four trials with a total number of 3461 patients met the inclusion criteria. Of these, data from 23 studies were available for analysis. Firstly, the results showed that follow-up pain relief rate was decreased slightly with the increase of the duration of each session and DOSE (r=-0.3414 and r=-0.3246, respectively), but those two factors had no correlation with the pain relief rate after treatment. Secondly, it showed that either lower frequency with 2 sessions/week and higher frequency greater than 2 sessions/week or DOSE of 30 mins/week can achieve higher pain relief rate after treatment. Thirdly, we found the rate of pain relief remained at a high level greater than 20% up to 18 weeks after the treatment, and then it dropped sharply below 10% with the follow-up extended. A positive relationship was found between study score and pain relief both in treatment and follow-up (r=0.4654 and r=0.3046, respectively). CONCLUSIONS: The effect of acupuncture varies greatly with the different schedules of acupuncture, so it is necessary to review and choose the appropriate schedule. Although the current work is based on a limited number of trials, the findings suggest that acupuncture has a dose and frequency effect presenting within a certain range, which would have considerable implications for the design and interpretation of clinical trials. More high-quality randomized controlled trials on acupuncture schedule research were needed for providing more definitive evidence.

The effect of hydration on the electronic structure and stability of the superalkali cation Li3.

The interaction of the superalkali cation Li3+ with water molecules, as well as the structures and stability of the resulting water complexes are theoretically studied at the MP2/6-311++G(d,p) level. A great number of geometrical configurations were obtained for the Li3+(H2O)n (n = 1-5) complexes and Li3+ is found to have a maximum coordination number of four. Natural population analysis shows that the charge distribution of Li3+ becomes seriously uneven upon interaction with five water molecules, so it loses ring conjugation and splits in the lowest-energy isomer of Li3+(H2O)5. Localized molecular orbital energy decomposition analysis indicates a dominant contribution of electrostatic interactions to the binding of water molecules to Li3+, which is similar to the case of lithium ion hydrates. However, as the number of water ligands reaches five, the contribution of the exchange-repulsion energy exhibits a sharp increase and even exceeds that of the electrostatic term.

Genotype and phenotype correlation in von Hippel-Lindau disease based on alteration of the HIF-α binding site in VHL protein.

PURPOSE: Von Hippel-Lindau (VHL) disease is a rare hereditary cancer syndrome that reduces life expectancy. We aimed to construct a more valuable genotype-phenotype correlation based on alterations in VHL protein (pVHL). METHODS: VHL patients (n = 339) were recruited and grouped based on mutation types: HIF-α binding site missense (HM) mutations, non-HIF-α binding site missense (nHM) mutations, and truncating (TR) mutations. Age-related risks of VHL-associated tumors and patient survival were compared. RESULTS: Missense mutations conferred an increased risk of pheochromocytoma (HR = 1.854, p = 0.047) compared with truncating mutations. The risk of pheochromocytoma was lower in the HM group than in the nHM group (HR = 0.298, p = 0.003) but was similar between HM and TR groups (HR = 0.901, p = 0.810). Patients in the nHM group had a higher risk of pheochromocytoma (HR = 3.447, p < 0.001) and lower risks of central nervous system hemangioblastoma (CHB) (HR = 0.700, p = 0.045), renal cell carcinoma (HR = 0.610, p = 0.024), and pancreatic tumor (HR = 0.382, p < 0.001) than those in the combined HM and TR (HMTR) group. Moreover, nHM mutations were independently associated with better overall survival (HR = 0.345, p = 0.005) and CHB-specific survival (HR = 0.129, p = 0.005) than HMTR mutations. CONCLUSION: The modified genotype-phenotype correlation links VHL gene mutation, substrate binding site, and phenotypic diversity (penetrance and survival), and provides more accurate information for genetic counseling and pathogenesis studies.

Transgelin-2 as a therapeutic target for asthmatic pulmonary resistance.

There is a clinical need for new bronchodilator drugs in asthma, because more than half of asthmatic patients do not receive adequate control with current available treatments. We report that inhibition of metallothionein-2 protein expression in lung tissues causes the increase of pulmonary resistance. Conversely, metallothionein-2 protein is more effective than ß2-agonists in reducing pulmonary resistance in rodent asthma models, alleviating tension in tracheal spirals, and relaxing airway smooth muscle cells (ASMCs). Metallothionein-2 relaxes ASMCs via transgelin-2 (TG2) and induces dephosphorylation of myosin phosphatase target subunit 1 (MYPT1). We identify TSG12 as a nontoxic, specific TG2-agonist that relaxes ASMCs and reduces asthmatic pulmonary resistance. In vivo, TSG12 reduces pulmonary resistance in both ovalbumin- and house dust mite-induced asthma in mice. TSG12 induces RhoA phosphorylation, thereby inactivating the RhoA-ROCK-MYPT1-MLC pathway and causing ASMCs relaxation. TSG12 is more effective than ß2-agonists in relaxing human ASMCs and pulmonary resistance with potential clinical advantages. These results suggest that TSG12 could be a promising therapeutic approach for treating asthma.

Risk factors for survival in patients with von Hippel-Lindau disease.

BACKGROUND: Historically, von Hippel-Lindau (VHL) disease is characterised by a poor survival. Although genotype-phenotype correlation has been described in many studies, the risk factors for VHL survival remain unclear. This study aims to evaluate the median survival of Chinese patients with VHL disease and explore whether VHL survival is influenced by genetic and clinical factors. METHODS: In this retrospective study, we recruited 340 patients from 127 VHL families. Kaplan-Meier plot and Cox regression model were used to evaluate the median survival and assess how survival was influenced by birth year, birth order, sex, family history, mutation type, onset age and first presenting symptom. RESULTS: The estimated median life expectancy for Chinese patients with VHL disease was 62 years. Patients with early-onset age, positive family history and truncating mutation types had poorer overall and VHL-related survival. Patients with haemangioblastoma as their first presenting symptom were related to a higher risk of death from central nervous system haemangioblastoma than those with abdominal lesions (HR 8.84, 95% CI 2.04 to 38.37, P=0.004). CONCLUSIONS: This largest VHL survival analysis indicates that onset age, family history, mutation type and first presenting symptom have an effect on the survival of patients with VHL disease, which is helpful to genetic counselling and clinical decision-making.

Shorter telomere length increases age-related tumor risks in von Hippel-Lindau disease patients.

Von Hippel-Lindau (VHL) disease is a rare autosomal dominant cancer syndrome caused by alterations of VHL gene. Patients are predisposed to develop pheochromocytomas and solid or cystic tumors of the central nervous system, kidney, pancreas, and retina. Remarkable phenotypic heterogeneity exits in organ involvement and tumor onset age between and within VHL families. However, no reliable markers have been found to predict the age-related tumor risks in VHL patients. A large Chinese cohort composed of 300 VHL patients and 92 healthy family controls was enrolled in our study. Blood relative telomere length was measured in 184 patients and all the controls available for genomic DNA samples. Age-related risks for the five major VHL-associated tumors were evaluated using Kaplan-Meier plots and Cox regression analysis. Differences in clinical phenotype were observed between Chinese cohort and the United Kingdom cohort. VHL patients showed significantly shorter telomere length than healthy family controls(P = 0.0183), and a positive correlation was found between telomere length and onset age of the five major tumors, respectively. Moreover, patients in the shorter telomere group (age-adjusted telomere length ≤ 0.44) suffered higher age-related risks for VHL-associated central nervous system hemangioblastomas (HR: 1.879, P = 0.004), renal cell carcinoma (HR: 2.126, P = 0.002) and pancreatic cyst and neuroendocrine tumors (HR: 2.093, P = 0.001). These results indicate that blood shorter telomere length is a new biomarker for age-related tumor risks in VHL patients, which will be crucial to genetic counseling and future research about the role of telomere shortening in the pathogenesis of VHL-associated tumors.

Higher programmed cell death 1 ligand 1 (PD-L1) mRNA level in clear cell renal cell carcinomas is associated with a favorable outcome due to the active immune responses in tumor tissues.

Renal cell carcinoma is one of the most common urological tumors. The role of programmed cell death 1 ligand 1 (PD-L1) in renal cell carcinomas in predicting outcome of the patients is yet unclear. We analyzed the clinical and RNA-seq data of 522 kidney clear cell cancer, 259 kidney papillary cell carcinoma and 66 kidney chromophobe patients from The Cancer Genome Atlas (TCGA) database. In kidney clear cell cancer patients with high PD-L1 mRNA level and low PD-L1 mRNA level in tumors, the median overall survival periods were 45.0 and 37.1 months respectively (p=0.002). Multivariate Cox regression tests found that PD-L1 mRNA level in tumor was an independent predictor for overall survival status in kidney clear cell cancer patients (HR=0.7, 95% CI 0.5-0.9, p=0.007). However, no significant difference in overall survival status was found between high and low PD-L1 groups in kidney papillary cell carcinoma and kidney chromophobe cohorts. Gene-set enrichment analysis on the data from databases of TCGA and GSE53757 dataset in Gene Expression Omnibus databases showed that several pathways relating to immunological functions were activated in kidney clear cell cancers with high PD-L1 mRNA expression, and glycolysis and epithelial-mesenchymal transition pathways relating to tumor progression and metastasis were increased in kidney clear cell cancers with low PD-L1 mRNA level. In conclusion, higher PD-L1 mRNA level in kidney clear cell cancer tissues was associated with a favorable outcome due to the higher immunological responses in tumor tissues.

Does Alkaline-Earth-Metal-Based Superalkali Exist?

A series of MkF2k-1+ (M = Mg, Ca; k = 2, 3) cations have been theoretically investigated to make a new attempt to design superalkali species. As expected, most of these cations were identified as pseudoalkali or even superalkali cations in view of their low electron affinities (EAs). The stability of these cationic clusters is indicated by considerable HOMO-LUMO gaps and positive dissociation energies. More intriguingly, these alkaline-earth-metal-based cations have advantages over alkali-metal-based superalkalis in two aspects: (1) they possess much larger binding energy values; (2) they can keep the chemical stability along with the increasing cluster size. Therefore, it is proposed here that the alkaline-earth-metal atoms could partner with halogens to construct stable cations of low EA value, which may add new candidates to the superalkali family.

On the feasibility of designing hyperalkali cations using superalkali clusters as ligands.

The possibility of using superalkali clusters instead of alkali atoms as ligands to design a class of cationic compounds, referred to as hyperalkali cations, has been examined by using gradient-corrected density functional theory. By taking typical superalkalis (FLi2, OLi3, and NLi4) as examples, a series of hyperalkali cations ML2+ [M = (super)halogen; L = superalkali] have been constructed and investigated. Calculational results show that all the superalkali moieties preserve their geometric and electronic integrity in these proposed cations. The stability of these studied cations is guaranteed by the strong ionic bonds between superalkali ligand and (super)halogen core, as well as their large highest occupied molecular orbital-lowest unoccupied molecular orbital gaps and positive dissociation energies. In particular, all these proposed cations possess lower vertical electron affinities (2.36-3.56 eV) than those of their corresponding cationic superalkali ligands, verifying their hyperalkali nature. We, therefore, hope that this study will provide an approach to obtain new species with excellent reducing capability by utilizing various superalkalis as building blocks.