A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression.

Human-specific insertions play important roles in human phenotypes and diseases. Here we reported a 446-bp insertion (Insert-446) in intron 11 of the TBC1D8B gene, located on chromosome X, and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome 5. Interestingly, Insert-446 was present in the human Neanderthal and Denisovans genomes, and was fixed in humans after human-chimpanzee divergence. We have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in macaques. In addition, over-expression TBC1D8B promoted cell proliferation and migration through "a dual finger" catalytic mechanism (Arg538 and Gln573) in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in vivo. Knockout of Insert-446 prevented cell proliferation and migration in cancer and normal cells. Our results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B gene. These findings provide a significant insight into the effects of human-specific insertions on evolution.

Optical bistability in a heterodimer composed of a quantum dot and a metallic nanoshell.

We theoretically explore the conditions for generating optical bistability (OB) in a heterodimer comprised of a semiconductor quantum dot (SQD) and a metallic nanoshell (MNS). The MNS is made of a metallic nanosphere as a core and a dielectric material as a shell. For the specific hybrid system considered, the bistable effect appears only if the frequency of the pump field is equal to (or slightly less than) the exciton frequency for a proper shell thickness. Bistability phase diagrams, when plotted, show that the dipole-induced bistable region can be greatly broadened by changing the shell thickness of the MNS in a strong exciton-plasmon coupling regime. In particular, we demonstrate that the multipole polarization not only narrows the bistable zone but also enlarges the corresponding thresholds for a given intermediate scaled pumping intensity. On the other hand, when the SQD couples strongly with the MNS, the multipole polarization can also significantly broaden the bistable region and induce a great suppression of the FWM (four-wave mixing) signal for a fixed shell thickness. These interesting findings offer a fresh understanding of the bistability conditions in an SQD/MNS heterodimer, and may be useful in the fabrication of high-performance and low-threshold optical bistable nanodevices.

A new core-shell-type nanoparticle loaded with paclitaxel/norcantharidin and modified with APRPG enhances anti-tumor effects in hepatocellular carcinoma.

Nanoparticle delivery systems have been shown to improve the therapeutic efficacy of anti-cancer drugs, including a variety of drugs for the treatment of hepatocellular carcinoma (HCC). However, the current systems show some limitations, and the delivery of more effective nanoparticle systems for anti-HCC drugs with better targeting ability are needed. Here, we created paclitaxel (PTX)/norcantharidin (NCTD)-loaded core-shell lipid nanoparticles modified with a tumor neovasculature-targeted peptide (Ala-Pro-Arg-Pro-Gly, APRPG) and investigated their anti-tumor effects in HCC. Core-shell-type lipid nanoparticles (PTX/NCTD-APRPG-NPs) were established by combining poly(lactic-co-glycolic acid) (PLGA)-wrapped PTX with phospholipid-wrapped NCTD, followed by modification with APRPG. For comparison, PTX-loaded PLGA nanoparticles (PTX-NPs) and PTX/NCTD-loaded core-shell-type nanoparticles without APRPG (PTX/NCTD-NPs) were prepared. The in vitro and in vivo anti-tumor effects were examined in HepG2 cells and tumor-bearing mice, respectively. Morphological and release characterization showed that PTX/NCTD-APRPG-NPs were prepared successfully and achieved up to 90% release of PTX in a sustained manner. Compared with PTX/NCTD-NPs, PTX/NCTD-APRPG-NPs significantly enhanced the uptake of PTX. Notably, the inhibition of proliferation and migration of hepatoma cells was significantly higher in the PTX/NCTD-APRPG-NP group than those in the PTX-NP and PTX/NCTD-NP groups, which reflected significantly greater anti-tumor properties as well. Furthermore, key molecules in cell proliferation and apoptosis signaling pathways were altered most in the PTX/NCTD-APRPG-NP group, compared with the PTX-NP and PTX/NCTD-NP groups. Collectively, PTX/NCTD-loaded core-shell lipid nanoparticles modified with APRPG enhance the effectiveness of anti-HCC drugs and may be an effective system for the delivery of anti-HCC drugs.

[Social Determinants Affecting Changes in Mental Health of Rural-Urban Migrant Population in Chengdu: An Oaxaca-Blinder Decomposition Analysis].

Objective: To investigate the social determinants that influenced the changes in the mental health of the rural-urban migrant population in Chengdu. Methods: Using data from two cross-sectional surveys, one conducted in 2009 and another, in 2018, of the rural-urban migrant population in Chengdu, we analyzed the social determinants of mental health affecting the rural-urban migrant population in Chengdu by multiple linear regression, and analyzed the contribution of changes in social determinants to the disparity in mental health over a decade using the Oaxaca-Blinder decomposition analysis. Results: This study included 3091 cases of rural-urban migrants in Chengdu, with 965 (31.22%) covered in the survey year of 2009 and 2126 (68.78%) covered in 2018. Multiple linear regression models were established with mental component summary (MCS) as the dependent variable, the social determinants of health as the independent variables, and gender, age, and survey year as covariates. The findings showed that being married ( ß=2.33, P<0.001), drinking 1-2 times per week ( ß=-1.42, P<0.05), illness within four weeks ( ß=-2.57, P<0.001), and hospitalization in the past year ( ß=-1.82, P<0.05), wage arrears ( ß=-1.67, P<0.05), job satisfaction ( ß=1.25, P<0.001), monthly housing costs (housing costs below monthly income: ß=-1.55, P=0.001; housing costs above monthly income: ß=-4.59, P=0.001) and housing condition ( ß=0.23, P<0.05) had significant impact on the MCS of the rural-urban migrant population. The results of the Oaxaca-Blinder decomposition method showed that the MCS disparity between the two surveys was -4.7660 points. With 2018 as the base year, the explainable parts accounted for 15.80%. Being married, decrease in the prevalence of illnesses within four weeks, and increased job satisfaction formed positive contribution to the improvement of the mental health, and increase in the proportion of monthly housing expenses formed negative contribution. Conclusion: Between 2009 and 2018, the mental health of the rural-urban migrant population in Chengdu showed improvement, and changes in marital status, illness within four weeks, job satisfaction, and monthly housing costs contributed to improvements in mental health during the period. Future intervention measures to promote the mental health of the floating population can be developed with the perspective of improving the social determinants of health in mind.

A case of a death caused by an atrial-oesophageal-thoracic fistula after radiofrequency ablation of atrial fibrillation.

The report is about a 49-year-old man with rheumatic heart disease and atrial fibrillation. He underwent mitral valve replacement, tricuspid valvuloplasty, and atrial fibrillation radiofrequency ablation in the hospital. He vomited blood on the 2nd postoperative day, and the bleeding gradually worsened thereafter. He had to have repeated drainage of large amounts of blood from his right thoracic cavity and digestive tract. He died suddenly after undergoing an oesophageal endoscopy on the 24th postoperative day. The autopsy revealed an atrial-oesophageal-thoracic fistula. By excluding the possibility of the fistula being caused by complications from nasoenteric feeding, tracheal intubation, and a foreign body ingestion, we determined that the atrial-oesophageal-thoracic fistula was a complication after radiofrequency ablation according to the finding of coagulation necrosis of the myocardial cells at the left atrium fistula. In addition, we also performed an elemental analysis on the radiofrequency ablation area and other cardiac tissues by scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) and found five metal elements, Cr, Cu, Zn, Mn, and Ti, which specifically existed in the radiofrequency ablation area. This finding has the potential to serve as new evidence for radiofrequency ablation and is a worthy direction of research.

Correlation Between IVIM-DWI Parameters and Pathological Classification of Idiopathic Orbital Inflammatory Pseudotumors: A Preliminary Study.

Objective: To investigate the correlation between intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and the pathological classification of idiopathic orbital inflammatory pseudotumors (IOIPs). Methods: Nineteen patients who were diagnosed with IOIPs (a total of 24 affected eyes) between November 2018 and December 2020 were included in the study. All the patients underwent magnetic resonance imaging orbital plain scans and IVIM-DWI multiparameter scans before an operation. The true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) values were obtained. Based on histopathology, the lesions were divided into three types: lymphocytic infiltration, fibrosclerotic, and mixed. The correlation between IVIM-DWI parameters and pathological classification was tested with the histopathological results as the gold standard. The data were analyzed using SPSS version 17.0, with P < 0.05 defined as significant. Results: Among the 19 patients (24 eyes) affected by IOIP, there were no significant differences between IOIP pathological classification and gender or age (P > 0.05). There were statistically significant differences between the D and f values for different pathological types of IOIP and IVIM parameters (P < 0.05), and there was no significant difference in D* value between the different pathological types (P > 0.05). Conclusion: The D and f values showed correlation with different types of IOIP, and the sensitivity of the D value was higher than that of the f value. The D* value showed no significant distinction between pathological types of IOIP.

Ultra-strong optical four-wave mixing signal induced by strong exciton-phonon and exciton-plasmon couplings.

We propose a scheme to generate ultra-strong four-wave mixing (FWM) signal based on a suspended monolayer graphene nanoribbon nanomechanical resonator (NR) coupled to an Au nanoparticle (NP). It is shown that, the FWM spectrum can switch among two-peaked, three-peaked, four-peaked or five-peaked via the modulation of exciton-phonon and exciton-plasmon couplings. This is mainly attributed to the vibrational properties of NR related to the exciton-phonon coupling, and the energy-level splitting of the localized exciton correlated to three classes of resonances consisting of three-photon resonance, Rayleigh Resonance, and AC-Stark atomic resonance. Especially, in a dual-strong coupling regime, the gains for these peaks can be as high as nine orders of magnitude (∼ 109) around the lower bistable threshold due to a combined effect of two couplings. Our findings not only offer an efficient way to measure the vibrational frequency of NR and the exciton-phonon coupling strength but also provide a possibility to fabricate high-performance optoelectronic nanodevices.

The high diversity of SARS-CoV-2-related coronaviruses in pangolins alerts potential ecological risks.

Understanding the zoonotic origin and evolution history of SARS-CoV-2 will provide critical insights for alerting and preventing future outbreaks. A significant gap remains for the possible role of pangolins as a reservoir of SARS-CoV-2 related coronaviruses (SC2r-CoVs). Here, we screened SC2r-CoVs in 172 samples from 163 pangolin individuals of four species, and detected positive signals in muscles of four Manis javanica and, for the first time, one M. pentadactyla. Phylogeographic analysis of pangolin mitochondrial DNA traced their origins from Southeast Asia. Using in-solution hybridization capture sequencing, we assembled a partial pangolin SC2r-CoV (pangolin-CoV) genome sequence of 22 895 bp (MP20) from the M. pentadactyla sample. Phylogenetic analyses revealed MP20 was very closely related to pangolin-CoVs that were identified in M. javanica seized by Guangxi Customs. A genetic contribution of bat coronavirus to pangolin-CoVs via recombination was indicated. Our analysis revealed that the genetic diversity of pangolin-CoVs is substantially higher than previously anticipated. Given the potential infectivity of pangolin-CoVs, the high genetic diversity of pangolin-CoVs alerts the ecological risk of zoonotic evolution and transmission of pathogenic SC2r-CoVs.

Efficacy of acupuncture therapy for improving anorexia in tumor patients: a Meta-analysi.

OBJECTIVE: To use evidence-based medicine to systematically evaluate the effectiveness and safety of acupuncture therapy for improving anorexia in tumor patients. METHODS: We queried the China National Knowledge Infrastructure Database (CNKI), China Science and Technology Journal Database (VIP), Wanfang Data, PubMed, Cochrane Library, and Embase databases to identify reports of randomized controlled trials (RCTs) that applied acupuncture therapy to improve anorexia in tumor patients, and used Rev Man 5.3 software to conduct a Meta-analysis of the effective rate, appetite score, Karnofsky Performance Status (KPS) score, Functional Assessment of Anorexia/Cachexia Therapy (FAACT) appetite scale, and body weight in each study. Subgroup analysis was conducted based on whether radiotherapy or chemotherapy were also administered. RESULTS: A total of 10 RCTs were included with a total of 648 patients, including 343 patients in the treatment group and 305 patients in the control group. The Meta-analysis results showed that the clinical efficacy, appetite score, KPS score, and FAACT score of the treatment group (which received acupuncture to improve appetite) were better than those of the control group, and the difference was statistically significant (P < 0.05); however, there was no statistically significant difference in body weight between the treatment group and the control group (P > 0.05). The results of the subgroup analysis showed that the effective rate and appetite score for patients with long-term and chronic loss of appetite who underwent acupuncture were better than those of the control group, and the difference was statistically significant (P < 0.05). CONCLUSIONS: Acupuncture therapy has good efficacy and safety in the treatment of anorexia in tumor patients, and it also has good efficacy and safety for long-term and chronic loss of appetite. The reliability and stability of the above results need to be confirmed by high-quality RCTs with larger sample sizes.

Three-dimensional-arterial spin labeling perfusion correlation with diabetes-associated cognitive dysfunction and vascular endothelial growth factor in type 2 diabetes mellitus rat.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has been strongly associated with an increased risk of developing cognitive dysfunction and dementia. The mechanisms of diabetes-associated cognitive dysfunction (DACD) have not been fully elucidated to date. Some studies proved lower cerebral blood flow (CBF) in the hippocampus was associated with poor executive function and memory in T2DM. Increasing evidence showed that diabetes leads to abnormal vascular endothelial growth factor (VEGF) expression and CBF changes in humans and animal models. In this study, we hypothesized that DACD was correlated with CBF alteration as measured by three-dimensional (3D) arterial spin labeling (3D-ASL) and VEGF expression in the hippocampus. AIM: To assess the correlation between CBF (measured by 3D-ASL and VEGF expression) and DACD in a rat model of T2DM. METHODS: Forty Sprague-Dawley male rats were divided into control and T2DM groups. The T2DM group was established by feeding rats a high-fat diet and glucose to induce impaired glucose tolerance and then injecting them with streptozotocin to induce T2DM. Cognitive function was assessed using the Morris water maze experiment. The CBF changes were measured by 3D-ASL magnetic resonance imaging. VEGF expression was determined using immunofluorescence. RESULTS: The escape latency time significantly reduced 15 wk after streptozotocin injection in the T2DM group. The total distance traveled was longer in the T2DM group; also, the platform was crossed fewer times. The percentage of distance in the target zone significantly decreased. CBF decreased in the bilateral hippocampus in the T2DM group. No difference was found between the right CBF value and the left CBF value in the T2DM group. The VEGF expression level in the hippocampus was lower in the T2DM group and correlated with the CBF value. The escape latency negatively correlated with the CBF value. The number of rats crossing the platform positively correlated with the CBF value. CONCLUSION: Low CBF in the hippocampus and decreased VEGF expression might be crucial in DACD. CBF measured by 3D-ASL might serve as a noninvasive imaging biomarker for cognitive impairment associated with T2DM.

[Impact of mild hypothermia therapy on hemodynamics during the induction stage in neonates with moderate to severe hypoxic-ischemic encephalopathy].

OBJECTIVE: To study the changes in hemodynamics during the induction stage of systemic mild hypothermia therapy in neonates with moderate to severe hypoxic-ischemic encephalopathy (HIE). METHODS: A total of 21 neonates with HIE who underwent systemic mild hypothermia therapy in the Department of Neonatology, Dongguan Children's Hospital Affiliated to Guangdong Medical University, from July 2017 to April 2020 were enrolled. The rectal temperature of the neonates was lowered to 34℃ after 1-2 hours of induction and maintained at this level for 72 hours using a hypothermia blanket. The impedance method was used for noninvasive hemodynamic monitoring, and the changes in heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), cardiac output (CO), cardiac index (CI), and total peripheral resistance (TPR) from the start of hypothermia induction to the achievement of target rectal temperature (34℃). Blood lactic acid (LAC) and resistance index (RI) of the middle cerebral artery were recorded simultaneously. RESULTS: The 21 neonates with HIE had a mean gestational age of (39.6±1.1) weeks, a mean birth weight of (3 439±517) g, and a mean 5-minute Apgar score of 6.8±2.0. From the start of hypothermia induction to the achievement of target rectal temperature (34℃), there were significant reductions in HR, CO, and CI (P < 0.05), while there was no significant change in SV and MAP (P > 0.05). There was a significant increase in TPR (P < 0.05) and a significant reduction in LAC (P < 0.05), while there was no significant change in RI (P > 0.05). CONCLUSIONS: The systemic mild hypothermia therapy may have a significant impact on hemodynamics in neonates with moderate to severe HIE, and continuous hemodynamic monitoring is required during the treatment.

[Correlation of gr/gr and b2/b3 deletions in the AZFc region of the Y-chromosome with recurrent spontaneous abortion].

OBJECTIVE: To investigate the association of gr/gr, b2/b3 and gr/gr with b1-2/b3-4 deletions (repetitions) in the AZFc region of the Y chromosome with recurrent spontaneous abortion (RSA). METHODS: Using the next-generation sequencing technology, we examined the men with indications of Y chromosome microdeletion at our center from June 2017 to March 2018 and excluded the common causes of RSA through inquiry and other related examinations. Totally, 170 cases of AZFc deletion (80 cases of gr/gr deletion, 75 cases of b2/b3 deletion, and 15 cases of gr/gr with b1-2/b3-4 deletion) were detected and included in the case group, and another 328 normal males enlisted as controls. We analyzed the correlation of Y chromosome microdeletions with the incidence rate of RSA. RESULTS: The incidence rate of RSA was significantly higher in the case group than in the normal controls (28.8% ï¼»49/170ï¼½ vs 13.1% ï¼»43/328ï¼½, P < 0.01), 22.5% (18/80) in the gr/gr deletion cases (P < 0.05), 30.7% (23/75) in the b2/b3 deletion cases (P < 0.01), and 53.3% (8/15) in the gr/gr with b1-2/b3-4 deletion cases (P < 0.01), remarkably lower in the gr/gr than in the gr/gr with b1-2/b3-4 deletion subgroup (P < 0.05), but with no statistically significant difference between the other subgroups. CONCLUSIONS: The gr/gr, b2/b3, and gr/gr with b1-2/b3-4 deletions (repetitions) in the AZFc region of the Y chromosome may cause recurrent spontaneous abortion.

Elevated Osteoprotegerin Concentration Predicts Increased Risk of Cardiovascular Mortality in Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: Studies have shown inconsistent results regarding the association between osteoprotegerin (OPG) concentration and cardiovascular mortality in patients with chronic kidney disease (CKD). This systematic review and meta-analysis aims to investigate the association between OPG concentration and cardiovascular mortality in patients with CKD. METHODS: Between January 1970 and February 2020, the PubMed, EMBASE, and Cochrane Library databases were searched for eligible studies investigating the association between OPG concentration and cardiovascular mortality in patients with CKD. Pooled hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated using random effects models. RESULTS: In total, 10 studies comprising 2,120 patients (including 1,723 receiving dialysis) with CKD were included. The included studies were considered to be of fair to high quality. Patients in the highest OPG concentration group had a significantly higher risk of cardiovascular mortality (4 studies; adjusted HR, 2.05; 95% CI, 1.39-3.00) than patients in the low OPG concentration group. An increase of 1 pmol/L in OPG concentration was associated with a 4% increased risk of cardiovascular mortality (6 studies; adjusted HR, 1.04; 95% CI, 1.02-1.07). CONCLUSION: Elevated OPG concentrations are associated with an increased risk of cardiovascular death in patients with CKD.

Controlled Synthesis of Au Nanocrystals-Metal Selenide Hybrid Nanostructures toward Plasmon-Enhanced Photoelectrochemical Energy Conversion.

A simple method for the controllable synthesis of Au nanocrystals-metal selenide hybrid nanostructures via amino acid guiding strategy is proposed. The results show that the symmetric overgrowth mode of PbSe shells on Au nanorods can be precisely manipulated by only adjusting the initial concentration of Pb2+. The shape of Au-PbSe hybrids can evolve from dumbbell-like to yolk-shell. Interestingly, the plasmonic absorption enhancement could be tuned by the symmetry of these hybrid nanostructures. This provides an effective pathway for maneuvering plasmon-induced energy transfer in metal-semiconductor hybrids. In addition, the photoactivities of Au-PbSe nanorods sensitized TiO2 electrodes have been further evaluated. Owing to the synergism between effective plasmonic enhancement effect and efficient interfacial charge transfer in these hybrid nanostructures, the Au-PbSe yolk-shell nanorods exhibit an outstanding photocurrent activity. Their photocurrent density is 4.38 times larger than that of Au-PbSe dumbbell-like nanorods under light irradiation at λ > 600 nm. As a versatile method, the proposed strategy can also be employed to synthesize other metal-selenide hybrid nanostructures (such as Au-CdSe, Au-Bi2Se3 and Au-CuSe).

Dual-channel bistable switch based on a monolayer graphene nanoribbon nanoresonator coupled to a metal nanoparticle.

We theoretically propose a dual-channel bistable switch based on a monolayer Z-shaped graphene nanoribbon nanoresonator (NR) coupled to a metal nanoparticle (MNP). We show that the bistable nonlinear absorption response can be realized due to a competition and combination of the exciton-plasmon and exciton-phonon interactions. We map out two-dimensional and three-dimensional bistability phase diagrams, which reveal clearly the dynamical evolution of the roles played by these two interactions in managing optical bistability (OB) at all stages. Specifically, the bistable switch proposed can be controlled via a single channel or dual channels by only adjusting the intensity or frequency of the pump field. In/outside these channels, the switch will be turned on/off. The results obtained here not only can be employed to measure precisely the distance between the MNP and the NR but also provide promising applications in optical switching and optical storage.

Comparative Transcriptome Analysis Reveals Stem Secondary Growth of Grafted Rosa rugosa 'Rosea' Scion and R. multiflora 'Innermis' Rootstock.

Grafted plant is a chimeric organism formed by the connection of scion and rootstock through stems, so stem growth and development become one of the important factors to affect grafted plant state. However, information regarding the molecular responses of stems secondary growth after grafting is limited. A grafted Rosa plant, with R. rugosa 'Rosea' as the scion (Rr_scion) grafted onto R. multiflora 'Innermis' as the stock (Rm_stock), has been shown to significantly improve stem thickness. To elucidate the molecular mechanisms of stem secondary growth in grafted plant, a genome-wide transcription analysis was performed using an RNA sequence (RNA-seq) method between the scion and rootstock. Comparing ungrafted R. rugosa 'Rosea' (Rr) and R. multiflora 'Innermis' (Rm) plants, there were much more differentially expressed genes (DEGs) identified in Rr_scion (6887) than Rm_stock (229). Functional annotations revealed that DEGs in Rr_scion are involved in two Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways: the phenylpropanoid biosynthesis metabolism and plant hormone signal transduction, whereas DEGs in Rm_stock were associated with starch and sucrose metabolism pathway. Moreover, different kinds of signal transduction-related DEGs, e.g., receptor-like serine/threonine protein kinases (RLKs), transcription factor (TF), and transporters, were identified and could affect the stem secondary growth of both the scion and rootstock. This work provided new information regarding the underlying molecular mechanism between scion and rootstock after grafting.

Enhanced Thermoelectric Performance in n-Type SrTiO3/SiGe Composite.

Silicon germanium (SiGe) alloys hold promise for thermoelectric power generation at high temperatures and have been applied in deep-space missions. However, enhancement of the dimensionless thermoelectric figure-of-merit (ZT) is still needed for practical civil applications of SiGe. In this work, we report high-performance oxide/SiGe bulk composites that were obtained via hot-press sintering of mixed powders composed of phosphorus (P)-doped SiGe prepared via mechanical alloying, using a ball-milling technique and La-Nb-doped SrTiO3 (La-Nb-STO). The La-Nb-STO powder was obtained from ball milling of a bulk La-Nb-STO sample that was sintered via hot pressing of hydrothermally synthesized La-Nb-STO powder. Controlling the amount of La-Nb-STO nanoparticles added to SiGe matrix increased the power factor by optimizing the electron concentration and mobility in the composite. In addition, compared with single-phase P-doped SiGe, the second phase decreased the thermal conductivity because of additional phonon scattering at the interface. As a result, a high ZT of 0.91 was realized in the n-type oxide/SiGe bulk composite at 1000 K, which was 18% larger than that for the typical materials used in space flight missions and 5% higher than the single-phase SiGe alloys obtained in the present study. The strategy used in this study could also be viable to further enhance the ZT of nanostructured n-type SiGe and SrTiO3-based oxide materials.

Circulating Osteoprotegerin Levels Independently Predict All-cause Mortality in Patients with Chronic Kidney Disease: a Meta-analysis.

Background: Studies have shown inconsistent results regarding the association between circulating osteoprotegerin (OPG) levels and all-cause mortality in patients with chronic kidney disease (CKD). The aim of this meta-analysis is to investigate the association between circulating OPG levels and all-cause mortality in patients with CKD. Methods: The PubMed, EMBASE and Cochrane Library databases were searched for eligible studies investigating the association between circulating OPG levels and all-cause mortality in patients with CKD. Pooled hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated using a random effects model. Results: In all, 13 studies that included 2,895 patients with CKD were included in this analysis. According to the meta-analysis, patients with the highest circulating OPG level had a significantly higher risk of all-cause mortality (7 studies; the adjusted HR, 1.88; 95% CI, 1.45 - 2.44) compared with patients with the lower circulating OPG level. An increase of 1 pmol/L in the circulating OPG level was associated with a 6% increased risk of all-cause mortality (7 studies; the adjusted HR, 1.06; 95% CI, 1.03-1.10). A subgroup analysis by dialysis methods suggested that an elevated circulating OPG level was independently associated with all-cause mortality in the HD only population. Conclusion: Elevated circulating OPG levels independently predict an increased risk of all-cause mortality in patients with CKD, especially in the HD only population.

Bioartificial liver support systems for acute liver failure: A systematic review and meta-analysis of the clinical and preclinical literature.

BACKGROUND: Acute liver failure (ALF) has a high mortality varying from 80% to 85% with rapid progress in multi-organ system failure. Bioartificial liver (BAL) support systems have the potential to provide temporary support to bridge patients with ALF to liver transplantation or spontaneous recovery. In the past decades, several BAL support systems have been conducted in clinical trials. More recently, concerns have been raised on the renovation of high-quality cell sources and configuration of BAL support systems to provide more benefits to ALF models in preclinical experiments. AIM: To investigate the characteristics of studies about BAL support systems for ALF, and to evaluate their effects on mortality. METHODS: Eligible clinical trials and preclinical experiments on large animals were identified on Cochrane Library, PubMed, and EMbase up to March 6, 2019. Two reviewers independently extracted the necessary information, including key BAL indicators, survival and indicating outcomes, and adverse events during treatment. Descriptive analysis was used to identify the characteristics of the included studies, and a meta-analysis including only randomized controlled trial (RCT) studies was done to calculate the overall effect of BAL on mortality among humans and large animals, respectively. RESULTS: Of the 30 selected studies, 18 were clinical trials and 12 were preclinical experiments. The meta-analysis result suggested that BAL might reduce mortality in ALF in large animals, probably due to the recent improvement of BAL, including the type, cell source, cell mass, and bioreactor, but seemed ineffective for humans [BAL vs control: relative risk (95% confidence interval), 0.27 (0.12-0.62) for animals and 0.72 (0.48-1.08) for humans]. Liver and renal functions, hematologic and coagulative parameters, encephalopathy index, and neurological indicators seemed to improve after BAL, with neither meaningful adverse events nor porcine endogenous retrovirus infection. CONCLUSION: BAL may reduce the mortality of ALF by bridging the gap between preclinical experiments and clinical trials. Clinical trials using improved BAL must be designed scientifically and conducted in the future to provide evidence for transformation.

Long-term toxicity, pharmacokinetics and immune effects of a recombinant adenovirus vaccine expressing human papillomavirus 16 E6 and E7 proteins (HPV16 E6E7-Ad5 Vac) in primates.

OBJECTIVE: This study aimed to: evaluate long-term toxicity and pharmacokinetic parameters; to identify the target organ of toxicity of a recombinant adenovirus vaccine expressing human papillomavirus 16 E6 and E7 proteins (HPV16 E6E7-Ad5 Vac) in primates; and to determine the specific immune response of this recombinant adenovirus vaccine. METHOD: HPV16 E6E7-Ad5 Vac (dose 4.68 × 109 IU/bottle) was administered to Macaca fascicularis (M. fascicularis) to evaluate its long-term toxicity. The Cynomolgus Monkeys were divided into a negative control group (sodium chloride injection group), a low-dose group (4.68 × 108 IU/macaque), and, a high-dose group (4.68 × 109 IU/macaque). The drugs were administered at intervals of once every three weeks (D1, D21, D42). The macaques were observed until the sixth week of the recovery period (D84) for safety and toxicological indicators and pharmacokinetic indicators. To study the specific immune response in Rhesus Macaque, empty viruses (rAd5-null) and buffer were inoculated as controls, respectively. Two doses of the vaccine were given at 1.0 × 108 IU/ml and 1.0 × 109 IU/ml and theHPV-16 E6-/HPV-16 E7-specific IFN-γ productions were measured. RESULTS: The macaques of both the high-dose group and the low-dose group did not exhibit any systemic toxic response. The administered safe dose of the vaccine was 4.68 × 109 IU per animal. Following vaccination, HPV16 E6/E7-specific antibodies were observed to be generated in both groups, indicating an immune response of the lymphocytes targeting HPV16 E6 and HPV16 E7 epitopes (specific NF-r) was elicited. The peak level of HPV-16 E6-/HPV-16 E7-specific IFN-γ production was observed in the ninth week.