Hemodynamic Effects of Tortuosity and Stenosis in Superficial Temporal Artery-Middle Cerebral Artery Bypass for Moyamoya Disease.

BACKGROUND: Superficial temporal artery (STA)-middle cerebral artery (MCA) bypass surgery has been widely adopted in treating moyamoya disease (MMD). Geometric variations including high tortuosity and stenosis exist in many cases, but the hemodynamic effects have not been comprehensively evaluated. We aim to evaluate the hemodynamic effects of bypass geometry variations based on patient-specific data. METHODS: In total, 17 patients with MMD who underwent STA-MCA bypass surgery with highly tortuous bypass geometry were included. For each patient, the original 3-dimensional structure of STA-MCA bypass was reconstructed from clinical imaging data. The bypass structure was virtually improved by removing the tortuosity and stenosis. Computational fluid dynamics simulation was performed on both bypass structures under identical patient-specific condition. The simulated hemodynamic parameters of the bypass and its distal branches were compared between the original and virtually improved bypass geometries in all cases using paired t-test or Wilcoxon signed-rank test. The changes of hemodynamic parameters were compared between the cases with and without mild-to-moderate stenosis (44.0-70.3% in diameter) in the bypass using t-test or Mann-Whitney U test. RESULTS: The virtual improvement of bypass geometry significantly increased the flow rate of the bypass and its distal branches (P < 0.05) and decreased the transcranial flow resistance (P < 0.05). The hemodynamic changes in cases with stenosis removal were significantly greater than those without stenosis (P < 0.05). CONCLUSIONS: High tortuosity and stenosis can significantly change the hemodynamics of STA-MCA bypass, and the optimization of bypass geometry deserves further consideration.

Phantom study of a self-shielded X-ray bone age assessment instrument against scattered radiation in children.

Hand-wrist radiography is the most common and accurate method for evaluating children's bone age. To reduce the scattered radiation of radiosensitive organs in bone age assessment, we designed a small X-ray instrument with radioprotection function by adding metal enclosure for X-ray shielding. We used a phantom operator to compare the scattered radiation doses received by sensitive organs under three different protection scenarios (proposed instrument, radiation personal protective equipment, no protection). The proposed instrument showed greater reduction in the mean dose of a single exposure compared with radiation personal protective equipment especially on the left side which was proximal to the X-ray machine (≥80.0% in eye and thyroid, ≥99.9% in breast and gonad). The proposed instrument provides a new pathway towards more convenient and efficient radioprotection.

The heterogeneity of signaling pathways and drug responses in intrahepatic cholangiocarcinoma with distinct genetic mutations.

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignancy among primary liver cancers, with an increasing overall incidence and poor prognosis. The intertumoral and intratumoral heterogeneity of ICC makes it difficult to find efficient drug therapies. Therefore, it is essential to identify tumor suppressor genes and oncogenes that induce ICC formation and progression. Here, we performed CRISPR/Cas9-mediated genome-wide screening in a liver-specific Smad4/Pten knockout mouse model (Smad4co/co;Ptenco/co;Alb-Cre, abbreviated as SPC), which normally generates ICC after 6 months, and detected that mutations in Trp53, Fbxw7, Inppl1, Tgfbr2, or Cul3 markedly accelerated ICC formation. To illustrate the potential mechanisms, we conducted transcriptome sequencing and found that multiple receptor tyrosine kinases were activated, which mainly upregulated the PI3K pathway to induce cell proliferation. Remarkably, the Cul3 mutation stimulated cancer progression mainly by altering the immune microenvironment, whereas other mutations promoted the cell cycle. Moreover, Fbxw7, Inppl1, Tgfbr2, and Trp53 also affect inflammatory responses, apelin signaling, mitotic spindles, ribosome biogenesis, and nucleocytoplasmic transport pathways, respectively. We further examined FDA-approved drugs for the treatment of liver cancer and performed high-throughput drug screening of the gene-mutant organoids. Different drug responses and promising drug therapies, including chemotherapy and targeted drugs, have been discovered for ICC.

Cryptochrome 1b represses gibberellin signaling to enhance lodging resistance in maize.

Maize (Zea mays L.) is one of the most important crops worldwide. Photoperiod, light quality, and light intensity in the environment can affect the growth, development, yield, and quality of maize. In Arabidopsis (Arabidopsis thaliana), cryptochromes are blue-light receptors that mediate the photocontrol of stem elongation, leaf expansion, shade tolerance, and photoperiodic flowering. However, the function of maize cryptochrome ZmCRY in maize architecture and photomorphogenic development remains largely elusive. The ZmCRY1b transgene product can activate the light signaling pathway in Arabidopsis and complement the etiolation phenotype of the cry1-304 mutant. Our findings show that the loss-of-function mutant of ZmCRY1b in maize exhibits more etiolation phenotypes under low blue light and appears slender in the field compared with wild-type plants. Under blue and white light, overexpression of ZmCRY1b in maize substantially inhibits seedling etiolation and shade response by enhancing protein accumulation of the bZIP transcription factors ELONGATED HYPOCOTYL 5 (ZmHY5) and ELONGATED HYPOCOTYL 5-LIKE (ZmHY5L), which directly upregulate the expression of genes encoding gibberellin (GA) 2-oxidase to deactivate GA and repress plant height. More interestingly, ZmCRY1b enhances lodging resistance by reducing plant and ear heights and promoting root growth in both inbred lines and hybrids. In conclusion, ZmCRY1b contributes blue-light signaling upon seedling de-etiolation and integrates light signals with the GA metabolic pathway in maize, resulting in lodging resistance and providing information for improving maize varieties.

SB Digestor: a tailored driver gene identification tool for dissecting heterogeneous Sleeping Beauty transposon-induced tumors.

Sleeping Beauty (SB) insertional mutagenesis has been widely used for genome-wide functional screening in mouse models of human cancers, however, intertumor heterogeneity can be a major obstacle in identifying common insertion sites (CISs). Although previous algorithms have been successful in defining some CISs, they also miss CISs in certain situations. A major common characteristic of these previous methods is that they do not take tumor heterogeneity into account. However, intertumoral heterogeneity directly influences the sequence read number for different tumor samples and then affects CIS identification. To precisely detect and define cancer driver genes, we developed SB Digestor, a computational algorithm that overcomes biological heterogeneity to identify more potential driver genes. Specifically, we define the relationship between the sequenced read number and putative gene number to deduce the depth cutoff for each tumor, which can reduce tumor complexity and precisely reflect intertumoral heterogeneity. Using this new tool, we re-analyzed our previously published SB-based screening dataset and identified many additional potent drivers involved in Brca1-related tumorigenesis, including Arhgap42, Tcf12, and Fgfr2. SB Digestor not only greatly enhances our ability to identify and prioritize cancer drivers from SB tumors but also substantially deepens our understanding of the intrinsic genetic basis of cancer.

Cullin-5 deficiency orchestrates the tumor microenvironment to promote mammary tumor development through CREB1-CCL2 signaling.

Breast cancer-associated gene 1 (Brca1) deficiency induces the onset of breast cancer formation, accompanied with extensive genetic alterations. Here, we used both the sleeping beauty transposon mutagenesis system and CRISPR-Cas9-mediated genome-wide screening in mice to identify potential genetic alterations that act synergistically with Brca1 deficiency to promote tumorignesis. Both approaches identified Cullin-5 as a tumor suppressor, whose mutation enabled Brca1-deficient cell survival and accelerated tumorigenesis by orchestrating tumor microenvironment. Cullin-5 suppresses cell growth through ubiquitylating and degrading adenosine 3',5'-monophosphate-responsive element binding protein 1 (CREB1), especially under protein damage condition. Meanwhile, Cullin-5 deficiency activated CREB1-CCL2 signaling and resulted in the accumulation of monocytes and polymorphonuclear myeloid-derived suppressor cells, reduction of T cells that benefit tumor progression in both Brca1-deficient cells and wild-type cells. Blocking CREB1 activity either through gene knockout or specific inhibitor treatment suppressed changes in the tumor microenvironment caused by Cullin-5 deficiency and blocked tumor progression.

Arabidopsis phytochromes A and B synergistically repress SPA1 under blue light.

In Arabidopsis, although studies have demonstrated that phytochrome A (phyA) and phyB are involved in blue light signaling, how blue light-activated phytochromes modulate the activity of the CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1)-SUPPRESSOR OF PHYA-105 (SPA1) E3 complex remains largely unknown. Here, we show that phyA responds to early and weak blue light, whereas phyB responds to sustainable and strong blue light. Activation of both phyA and phyB by blue light inhibits SPA1 activity. Specifically, blue light irradiation promoted the nuclear import of both phytochromes to stimulate their binding to SPA1, abolishing SPA1's interaction with LONG HYPOCOTYL 5 (HY5) to release HY5, which promoted seedling photomorphogenesis.

The Electrical Conductivity and Mechanical Properties of Monolayer and Multilayer Nanofibre Membranes from Different Fillers: Calculated Based on Parallel Circuit.

Advanced research on improving the performance of conductive polymer composites is essential to exploring their potential in various applications. Thus, in this study, the electrical conductivity of multilayer nanofibre membranes composed of polyvinyl alcohol (PVA) with different electroconductive fillers content including zinc oxide (ZnO), multiwalled carbon nanotubes (MWNTs), and Ferro ferric oxide (Fe3O4), were produced via electrospinning. The tensile property and electrical conductivity of monolayer membranes were explored. The results showed that PVA with 2 wt.% MWNTs nanofibre membrane has the best conductivity (1.0 × 10-5 S/cm) and tensile strength (29.36 MPa) compared with other fillers. Meanwhile, the combination of multilayer membrane ZnO/Fe3O4/Fe3O4/MWNTs/ZnO showed the highest conductivity (1.39 × 10-5 S/cm). The parallel circuit and calculation of parallel resistance were attempted to demonstrate the conductive mechanism of multilayer membranes, which can predict the conductivity of other multilayer films. The production of multilayer composites that enhance electrical conductivity and improve conductive predictions was successfully explored.

HFR1, a bHLH Transcriptional Regulator from Arabidopsis thaliana, Improves Grain Yield, Shade and Osmotic Stress Tolerances in Common Wheat.

Common wheat, Triticum aestivum, is the most widely grown staple crop worldwide. To catch up with the increasing global population and cope with the changing climate, it is valuable to breed wheat cultivars that are tolerant to abiotic or shade stresses for density farming. Arabidopsis LONG HYPOCOTYL IN FAR-RED 1 (AtHFR1), a photomorphogenesis-promoting factor, is involved in multiple light-related signaling pathways and inhibits seedling etiolation and shade avoidance. We report that overexpression of AtHFR1 in wheat inhibits etiolation phenotypes under various light and shade conditions, leading to shortened plant height and increased spike number relative to non-transgenic plants in the field. Ectopic expression of AtHFR1 in wheat increases the transcript levels of TaCAB and TaCHS as observed previously in Arabidopsis, indicating that the AtHFR1 transgene can activate the light signal transduction pathway in wheat. AtHFR1 transgenic seedlings significantly exhibit tolerance to osmotic stress during seed germination compared to non-transgenic wheat. The AtHFR1 transgene represses transcription of TaFT1, TaCO1, and TaCO2, delaying development of the shoot apex and heading in wheat. Furthermore, the AtHFR1 transgene in wheat inhibits transcript levels of PHYTOCHROME-INTERACTING FACTOR 3-LIKEs (TaPIL13, TaPIL15-1B, and TaPIL15-1D), downregulating the target gene STAYGREEN (TaSGR), and thus delaying dark-induced leaf senescence. In the field, grain yields of three AtHFR1 transgenic lines were 18.2-48.1% higher than those of non-transgenic wheat. In summary, genetic modification of light signaling pathways using a photomorphogenesis-promoting factor has positive effects on grain yield due to changes in plant architecture and resource allocation and enhances tolerances to osmotic stress and shade avoidance response.

Vibration of Tympanic Membrane Influenced by Middle Ear Fluid.

HYPOTHESIS: The amount and viscosity of middle ear fluid probably influences the vibration function of the tympanic membrane (TM). BACKGROUND: There has been much research into the mechanisms of hearing loss resulting from middle ear fluid in the previous study. However, further study is required to understand how the middle ear fluid affects the vibration function of the TM. METHODS: Tests on a TM in a fresh cadaveric human temporal bone specimen under different simulated conditions were carried out. Saline (1 cSt) and silicone oil (100 cSt, 1 000 cSt, 12 500 cSt) were used to simulate middle ear fluid. The fluid approximately contacted 50% or 100% of TM, which was proportional to the fluid amount. Induced by stimulus signal with frequency domain from 0.25 to 8 kHz, the vibration at 6 points of the TM was measured by laser Doppler vibrometer (LDV), respectively. Data acquisition and processing were accomplished by self-developed software. RESULTS: With the increase of the fluid amount, the magnitude of velocity transfer function reduced across all frequencies. The effect of fluid viscosity on the TM vibration varied and reduced in a complicated way when the fluid viscosity changed. CONCLUSION: Increasing fluid amount will significantly reduce the TM movement. The effect of fluid viscosity on the TM vibration was nonlinear and related to the fluid amount. The vibration at each point on the TM is frequency-dependent.

[Magnet Quench Factors in Ramping-up Procedure].

Ramping-up is the magnet current injection procedure which is under the control of resistance, voltage, current lead temperature, magnet pressure, temperature and so on. In this procedure, the factors related to the stability of the magnet such as, magnet temperature, pressure and currents are constantly changing. This procedure is the main step which the magnet-quench occurs in. This study uses the data collected during 7 years and SIMENS MRI ramping-up theory, in order to help engineers understand the key factors to reduce the magnet quench during the ramping up procedure.

Patient-Derived Organoids Can Guide Personalized-Therapies for Patients with Advanced Breast Cancer.

Most breast cancers at an advanced stage exhibit an aggressive nature, and there is a lack of effective anticancer options. Herein, the development of patient-derived organoids (PDOs) is described as a real-time platform to explore the feasibility of tailored treatment for refractory breast cancers. PDOs are successfully generated from breast cancer tissues, including heavily treated specimens. The microtubule-targeting drug-sensitive response signatures of PDOs predict improved distant relapse-free survival for invasive breast cancers treated with adjuvant chemotherapy. It is further demonstrated that PDO pharmaco-phenotyping reflects the previous treatment responses of the corresponding patients. Finally, as clinical case studies, all patients who receive at least one drug predicate to be sensitive by PDOs achieve good responses. Altogether, the PDO model is developed as an effective platform for evaluating patient-specific drug sensitivity in vitro, which can guide personal treatment decisions for breast cancer patients at terminal stage.

Utilisation of community care services and self-rated health among elderly population in China: a survey-based analysis with propensity score matching method.

BACKGROUND: Elderly care and elderly health are the enormous challenges in such an aging society as China. Community care services have been developing rapidly in recent years in China as an increasingly mainstream care resource to promote elderly health. The purpose of this study is to examine the association between using community care services and self-rated health among Chinese elderly. METHODS: A cross-sectional survey was conducted in 2019 and 612 elderly people from China's Shaanxi province were enrolled. The binary logistic regression was first employed to explore the association between community care services utilisation and elderly health. Given the potential selection bias issue, the propensity score matching method was hired to generate comparable samples between participants who used these services and participants who didn't, and further examine the health benefits of using four types of services. RESULTS: The results of the binary logistic regression showed that the use of community care services predicted a better health status of elderly individuals. Overall, the results of the propensity score matching method showed the similar results. Specifically, with the nearest neighbors matching algorithm, using daily care services was significantly associated with a 0.246 increase in the self-rated health of the elderly (T = 1.83). For medical care services, the mean of self-rated health of elderly individuals who used these services was 3.542, significantly higher than those who didn't (T = 2.15). For spiritual comfort services, elderly individuals using these services showed a significant increase by 0.280 in the self-rated health (T = 1.82). For social and recreational services, the result of the nearest neighbor matching method was not statistically significant, while the results of kernel matching method and the mahalanobis matching method showed a significant increase in the self-rated health among elderly individuals using these services (T = 2.03, T = 2.03, respectively). All the estimated results passed the Rosenbaum bounds analysis and were not sensitive to hidden bias. CONCLUSIONS: Using community care services improved the self-rated health of the elderly. More effective measures may be implemented to increase access to care resources for senior citizens, and further improve their health status.

NIR-II-activated biocompatible hollow nanocarbons for cancer photothermal therapy.

Photothermal therapy has attracted extensive attentions in cancer treatment due to its precise spatial-temporal controllability, minimal invasiveness, and negligible side effects. However, two major deficiencies, unsatisfactory heat conversion efficiency and limited tissue penetration depth, hugely impeded its clinical application. In this work, hollow carbon nanosphere modified with polyethylene glycol-graft-polyethylenimine (HPP) was elaborately synthesized. The synthesized HPP owns outstanding physical properties as a photothermal agent, such as uniform core-shell structure, good biocompatibility and excellent heat conversion efficiency. Upon NIR-II laser irradiation, the intracellular HPP shows excellent photothermal activity towards cancer cell killing. In addition, depending on the large internal cavity of HPP, the extended biomedical application as drug carrier was also demonstrated. In general, the synthesized HPP holds a great potential in NIR-II laser-activated cancer photothermal therapy.

Integrated transcriptome and proteome analysis reveals potential mechanisms for differential abdominal fat deposition between divergently selected chicken lines.

Genetic selection for meat production performance of broilers concomitantly causes excessive abdominal fat deposition, accompanied by several adverse effects, such as the reduction of feed conversion efficiency and reproduction performance. Our previous studies have identified important genes regulating chicken fat deposition, using the Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF) as an animal model. However, the molecular mechanism underlying fat deposition differences between fat and lean broilers remains largely unknown. Here, we integrated the transcriptome (RNA-Seq) and quantitative proteome (isobaric tags for relative and absolute quantitation, iTRAQ) profiling analyses on abdominal fat tissues from NEAUHLF chicken lines. Differentially expressed genes (2167 DEGs, corrected p-value < 0.01) and differentially abundant proteins (199 DAPs, corrected p-value < 0.05) were identified in lean line compared to fat line. Down-regulated DEGs and DAPs mainly enriched in pathways related to fatty acid metabolism, fatty acid biosynthesis, and PPAR signaling, and interestingly, up-regulated DEGs and DAPs enriched both in lysosome pathway. Moreover, numerous key DEGs and DAPs involved in long-chain fatty acid uptake, in situ lipogenesis (fatty acid and cholesterol synthesis), and lipid droplet accumulation were discovered after integrated transcriptome and proteome analysis. SIGNIFICANCE: Excessive abdominal fat deposition critically affects the health of broilers and causes economic loss to broiler producers, but the molecular mechanism of abdominal fat deposition is still unclear in chicken. We identified key DEGs/DAPs and potential pathways through an integration of chicken abdominal fat tissues transcriptome and proteome analyses. Our findings will facilitate a better revealing the mechanism and provide a novel insight into abdominal fat content discrepancy between the fat and lean chicken lines.

Genome-wide identification and expression analysis of late embryogenesis abundant protein-encoding genes in rye (Secale cereale L.).

Late embryogenesis abundant (LEA) proteins are members of a large and highly diverse family that play critical roles in protecting cells from abiotic stresses and maintaining plant growth and development. However, the identification and biological function of genes of Secale cereale LEA (ScLEA) have been rarely reported. In this study, we identified 112 ScLEA genes, which can be divided into eight groups and are evenly distributed on all rye chromosomes. Structure analysis revealed that members of the same group tend to be highly conserved. We identified 12 pairs of tandem duplication genes and 19 pairs of segmental duplication genes, which may be an expansion way of LEA gene family. Expression profiling analysis revealed obvious temporal and spatial specificity of ScLEA gene expression, with the highest expression levels observed in grains. According to the qRT-PCR analysis, selected ScLEA genes were regulated by various abiotic stresses, especially PEG treatment, decreased temperature, and blue light. Taken together, our results provide a reference for further functional analysis and potential utilization of the ScLEA genes in improving stress tolerance of crops.

Impact of Economic Accessibility on Realized Utilization of Home-Based Healthcare Services for the Older Adults in China.

Home-based healthcare service has gradually become the most important model to cope with aging in China. However, the contradiction between oversupply and insufficient demand of healthcare services is becoming increasingly serious. How to effectively improve the realized utilization of healthcare resources has become a key issue in the development of healthcare services. Based on the social background of "getting old before getting rich", this article explores the relationship between economic accessibility and realized utilization, and finds that the impact of economic accessibility on realized utilization is inverted U-shaped, not a linear positive effect. In addition, considering the moderating role of family support, it is found that family support can strengthen the inverted U-shaped effect of economic accessibility on realized utilization. Therefore, exerting the role of family and improving economic accessibility can effectively solve the dilemma of low utilization of healthcare services.

A high-quality genome assembly highlights rye genomic characteristics and agronomically important genes.

Rye is a valuable food and forage crop, an important genetic resource for wheat and triticale improvement and an indispensable material for efficient comparative genomic studies in grasses. Here, we sequenced the genome of Weining rye, an elite Chinese rye variety. The assembled contigs (7.74 Gb) accounted for 98.47% of the estimated genome size (7.86 Gb), with 93.67% of the contigs (7.25 Gb) assigned to seven chromosomes. Repetitive elements constituted 90.31% of the assembled genome. Compared to previously sequenced Triticeae genomes, Daniela, Sumaya and Sumana retrotransposons showed strong expansion in rye. Further analyses of the Weining assembly shed new light on genome-wide gene duplications and their impact on starch biosynthesis genes, physical organization of complex prolamin loci, gene expression features underlying early heading trait and putative domestication-associated chromosomal regions and loci in rye. This genome sequence promises to accelerate genomic and breeding studies in rye and related cereal crops.

Rural-urban and gender differences in the association between community care services and elderly individuals' mental health: a case from Shaanxi Province, China.

BACKGROUND: While community care services have been developing rapidly as a new way to meet the growing demands of elderly individuals in China, their health benefits are virtually unknown. Thus, the aim of this study was to examine the Chinese elderly individuals' utilisation of community care services and its association with the mental health with comparing rural-urban and gender differences. METHODS: For this 2019 cross-sectional study, 687 elderly people from 7 counties (districts) of China's Shaanxi province were enrolled. Respondents' mental health level was assessed using a self-reported mental health measure. Four categories of community care services utilisation were examined: daily care services, medical care services, social and recreational services and spiritual comfort services. The binary logistic regression model was used in examining the association between community care services utilisation and mental health. RESULTS: Our results showed that there was a noted difference in mental health level between the male and female groups. Utilisation of medical care services and social and recreational services was significantly higher in the rural group than that in the urban group. Regression analysis showed that utilisation of daily care services (ß = 0.809, p = 0.008) and social and recreational service (ß = 0.526, p = 0.035) was significantly and positively associated with elderly individuals' mental health level. Specifically, daily care services utilisation predicted a better mental health of the rural elderly (ß = 1.051, p = 0.036) and the male elderly (ß = 1.133, p = 0.053), while social and recreational services utilisation predicted a better mental health of the urban elderly (ß = 0.927, p = 0.008) and the female elderly (ß = 0.864, p = 0.007). CONCLUSIONS: Our findings indicated varied levels of community care services utilisation and mental health are common among the elderly people in China. Community care services utilisation has a positive, albeit selective, association with elderly individuals' mental health. Further policies should strengthen the equitable development of high-quality community care services in urban and rural areas to improve the mental health of elderly individuals, and focus more on gender differences in terms of community care services needs.