Orthostatic blood pressure changes do not influence cognitive outcomes following intensive blood pressure control.

BACKGROUND: Effects of intensive blood pressure (BP) control on cognitive outcomes in patients with excess orthostatic BP changes are unclear. We aimed to evaluate whether orthostatic BP changes modified the effects of BP intervention on cognitive impairment. METHODS: We analyzed 8547 participants from the Systolic Blood Pressure Intervention Trial Memory and cognition IN Decreased Hypertension. Associations between orthostatic BP changes and incident cognitive outcomes were evaluated by restricted cubic spline curves based on Cox models. The interactions between orthostatic BP changes and intensive BP intervention were assessed. RESULTS: The U-shaped associations were observed between baseline orthostatic systolic BP changes and cognitive outcomes. However, there were insignificant interactions between either change in orthostatic systolic BP (P for interaction = 0.81) or diastolic BP (P for interaction = 0.32) and intensive BP intervention for the composite outcome of probable dementia or mild cognitive impairment (MCI). The hazard ratio of intensive versus standard target for the composite cognitive outcome was 0.82 (95% CI 0.50-1.35) in those with an orthostatic systolic BP reduction of >20 mmHg and 0.41 (95% CI 0.21-0.80) in those with an orthostatic systolic BP increase of >20 mmHg. Results were similar for probable dementia and MCI. The annual changes in global cerebral blood flow (P for interaction = 0.86) consistently favored intensive BP treatment across orthostatic systolic BP changes. CONCLUSION: Intensive BP control did not have a deteriorating effect on cognitive outcomes among hypertensive patients experiencing significant postural BP changes.

Coprocessed heterogeneous near-infrared lasers on thin-film lithium niobate.

Thin-film lithium niobate (TFLN) is an attractive platform for photonic applications on account of its wide bandgap, its large electro-optic coefficient, and its large nonlinearity. Since these characteristics are used in systems that require a coherent light source, size, weight, power, and cost can be reduced and reliability enhanced by combining TFLN processing and heterogeneous laser fabrication. Here, we report the fabrication of laser devices on a TFLN wafer and also the coprocessing of five different GaAs-based III-V epitaxial structures, including InGaAs quantum wells and InAs quantum dots. Lasing is observed at wavelengths near 930, 1030, and 1180 nm, which, if frequency-doubled using TFLN, would produce blue, green, and orange visible light. A single-sided power over 25 mW is measured with an integrating sphere.

Characterization and clinical implications of different malignant transformation patterns in diffuse low-grade gliomas.

Malignant transformation (MT) of low-grade gliomas (LGGs) to a higher-grade variant seems inevitable, yet it remains unclear which LGG patients will progress to grade 3 or even directly to grade 4 after receiving a long course of treatment. To elucidate this, we conducted a retrospective cohort study based on 229 adults with recurrent LGG. Our study aimed to disclose the characteristics of different MT patterns and to build predictive models for patients with LGG. Patients were allocated into group 2-2 (n = 81, 35.4%), group 2-3 (n = 91, 39.7%), and group 2-4 (n = 57, 24.9%), based on their MT patterns. Patients who underwent MT showed lower Karnofsky performance scale (KPS) scores, larger tumor sizes, smaller extents of resection (EOR), higher Ki-67 indices, lower rates of 1p/19q codeletion, but higher rates of subventricular involvement, radiotherapy, chemotherapy, astrocytoma, and post-progression enhancement (PPE) compared with those in group 2-2 (p < 0.01). On multivariate logistic regression, 1p/19q codeletion, Ki-67 index, radiotherapy, EOR, and KPS score were independently associated with MT (p < 0.05). Survival analyses demonstrated that patients in group 2-2 had the longest survival, followed by group 2-3 and then group 2-4 (p < 0.0001). Based on these independent parameters, we constructed a nomogram model that exhibited superior potential (sensitivity: 0.864, specificity: 0.814, and accuracy: 0.843) compared with PPE in early prediction of MT. Combining the factors of 1p/19q codeletion, Ki-67 index, radiotherapy, EOR, and KPS score that were presented at initial diagnosis could precisely forecast the subsequent MT patterns of patients with LGG.

Intratumoral calcification: not only a diagnostic but also a prognostic indicator in oligodendrogliomas.

OBJECTIVE: Calcification is a hallmark characteristic of oligodendroglioma (ODG) that may be used as a diagnostic factor, but its prognostic implications remain unclear. This study aimed to investigate the features of calcified ODGs and to evaluate the differences in survival between patients with calcified and noncalcified ODGs. METHODS: We retrospectively reviewed the records of 305 consecutive patients who were diagnosed with IDH-mutant, 1p/19q codeleted ODG at our institution from July 2009 to August 2020. Patients with intratumoral calcification were identified. The clinical, radiologic, and molecular features of the patients in the calcified group and noncalcified group were recorded. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: Of the 305 patients, 112 (36.7%) were confirmed to have intratumoral calcification. Compared to ODGs without calcification, ODGs with calcifications had a larger tumor diameter; lower degree of resection; higher tumor grade; higher MGMT methylation level; higher Ki-67 index; and higher rates of midline crossing, enhancement, cyst, and 1q/19p copolysomy, and patients with calcification were more likely to receive chemoradiotherapy. ODGs with T2 hypointense calcification had a higher Hounsfield unit (HU) value on CT scans, and a lower degree of resection. Patients with T2 hypointense calcification ODGs had a shorter survival than those with non-hypointense calcification ODGs. ODGs with calcification and cysts showed a higher Ki-67 index, tumor grade, and enhanced rate, and the patients had an unfavorable overall survival (OS). Calcification was found to be a negative prognostic factor for both progression-free survival (PFS) and OS by univariate analysis, which was confirmed by the Cox proportional hazard model. CONCLUSIONS: Calcification is a useful negative prognostic factor for PFS and OS in patients with ODGs and could therefore be helpful in guiding personalized treatment and predicting patient prognosis. CLINICAL RELEVANCE STATEMENT: Calcification can serve as an independent prognostic factor for patients with oligodendroglioma and shows a vital role in guiding individualized treatment. KEY POINTS: • Intratumoral calcification is an independent negative prognostic risk factor for progression-free survival and overall survival in oligodendroglioma patients. • Calcifications in oligodendroglioma can be divided into hypointense and non-hypointense subtypes based on T2-weighted imaging, and patients with T2-hypointense calcification oligodendrogliomas have worse prognosis. • Calcification concurrent with cysts indicates a more aggressive phenotype of oligodendrogliomas and a significantly reduced survival rate.

The sinuous, wave-like intratumoral-wall sign is a sensitive and specific radiological biomarker for oligodendrogliomas.

OBJECTIVES: The purpose of this study was to investigate the clinical utility of the sinuous, wave-like intratumoral-wall (SWITW) sign on T2WI in diagnosing isocitrate dehydrogenase (IDH) mutant and 1p/19q codeleted (IDHmut-Codel) oligodendrogliomas, for which a relatively conservative resection strategy might be sufficient due to a better response to chemoradiotherapy and favorable prognosis. METHODS: Imaging data from consecutive adult patients with diffuse lower-grade gliomas (LGGs, histological grades 2-3) in Beijing Tiantan Hospital (December 1, 2013, to October 31, 2021, BTH set, n = 711) and the Cancer Imaging Archive (TCIA) LGGs set (n = 117) were used to develop and validate our findings. Two independent observers assessed the SWITW sign and some well-reported discriminative radiological features to establish a practical diagnostic strategy. RESULTS: The SWITW sign showed satisfying sensitivity (0.684 and 0.722 for BTH and TCIA sets) and specificity (0.938 and 0.914 for BTH and TCIA sets) in defining IDHmut-Codels, and the interobserver agreement was substantial (κ 0.718 and 0.756 for BTH and TCIA sets). Compared to calcification, the SWITW sign improved the sensitivity by 0.28 (0.404 to 0.684) in the BTH set, and 81.0% (277/342) of IDHmut-Codel cases demonstrated SWITW and/ or calcification positivity. Combining the SWITW sign, calcification, low ADC values, and other discriminative features, we established a concise and reliable diagnostic protocol for IDHmut-Codels. CONCLUSIONS: The SWITW sign was a sensitive and specific imaging biomarker for IDHmut-Codels. The integrated protocol provided an explicable, efficient, and reproducible method for precise preoperative diagnosis, which was essential to guide individualized surgical plan-making. KEY POINTS: • The SWITW sign was a sensitive and specific imaging biomarker for IDHmut-Codel oligodendrogliomas. • The SWITW sign was more sensitive than calcification and an integrated strategy could improve diagnostic sensitivity for IDHmut-Codel oligodendrogliomas. • Combining SWITW, calcification, low ADC values, and other discriminative features could make a precise preoperative diagnosis for IDHmut-Codel oligodendrogliomas.

Real-time measurement of the trans-epithelial electrical resistance in an organ-on-a-chip during cell proliferation.

The trans-epithelial electrical resistance (TEER) is widely used to quantitatively evaluate cellular barrier function at the organ level in vitro. The measurement of the TEER in organ-on-chips (organ chips) plays a significant role in medical and pharmacological research. However, due to the limitation of the electrical equivalent model for organ chips, the existing TEER measurements usually neglect the changes of the TEER during cell proliferation, resulting in the low accuracy of the measurements. Here, we proposed a new whole-region model of the TEER and developed a real-time TEER measurement system that contains an organ chip with a plate electrode. A whole region circuit model considering the impedance of the non-cell covered region was also established, which enables TEER measurements to be independent of the changes in the cell covered region. The impedance of the non-cell covered region is here attributed to the resistance of the porous membrane. By combining the real-time measurement system and the whole region model, subtle changes in cellular activity during the proliferation stage were measured continuously every 6 minutes and a more sensitive TEER response was obtained. Furthermore, the TEER measurement accuracy was also verified by the real-time measurement of the TEER with stimulation using the permeability enhancer ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA). The obtained results indicated that the new proposed whole region model and the real-time measurement system have higher accuracy and greater sensitivity than the traditional model.

A parylene-mediated plasmonic-photonic hybrid fiber-optic sensor and its instrumentation for miniaturized and self-referenced biosensing.

With the development of advanced nanofabrication techniques over the past decades, different nanostructure-based plasmonic fiber-optic sensors have been developed and have presented a low limit of detection for various biomolecules. However, owing to both the dependence on complex equipment and the trade-off between the fabrication cost and sensing performance, nanostructured plasmonic fiber-optic sensors are rarely used outside laboratories. To facilitate wider application of the plasmonic fiber-optic sensors, a parylene-mediated hybrid plasmonic-photonic cavity-based sensor was developed. Compared with a similar plasmonic sensor which only works in the plasmonic mode, the proposed hybrid sensor shows a higher reproducibility (CV < 2.5%) due to its resistance to fabrication variations. Meanwhile, a self-referenced detection mechanism and a novel miniaturized system were developed to adapt to the hybrid resonance sensor. The entire system only has a weight of 263 g, and a size of 12 cm × 10 cm × 8 cm, and is especially suitable for outdoor applications in a handheld manner. In experiments, a high refractive index sensitivity of 3.148 RIU-1 and real-time biomolecule monitoring at nanomolar concentrations were achieved by the proposed system, further confirming the potential of the miniaturized system as a candidate for point-of-care health diagnostics outside laboratories.

Identification of atrial fibrillation phenotypes at low risk of stroke in patients with CHA2DS2-VASc ≥2: Insight from the China-AF study.

OBJECTIVE: Patients with atrial fibrillation (AF) are highly heterogeneous, and current risk stratification scores are only modestly good at predicting an individual's stroke risk. We aim to identify distinct AF clinical phenotypes with cluster analysis to optimize stroke prevention practices. METHODS: From the prospective Chinese Atrial Fibrillation Registry cohort study, we included 4337 AF patients with CHA2 DS2 -VASc≥2 for males and 3 for females who were not treated with oral anticoagulation. We randomly split the patients into derivation and validation sets by a ratio of 7:3. In the derivation set, we used outcome-driven patient clustering with metric learning to group patients into clusters with different risk levels of ischemic stroke and systemic embolism, and identify clusters of patients with low risks. Then we tested the results in the validation set, using the clustering rules generated from the derivation set. Finally, the survival decision tree was applied as a sensitivity analysis to confirm the results. RESULTS: Up to the follow-up of 1 year, 140 thromboembolic events (ischemic stroke or systemic embolism) occurred. After supervised metric learning from six variables involved in CHA2 DS2 -VASc scheme, we identified a cluster of patients (255/3035, 8.4%) at an annual thromboembolism risk of 0.8% in the derivation set. None of the patients in the low-risk cluster had prior thromboembolism, heart failure, diabetes, or age older than 70 years. After applying the regularities from metric learning on the validation set, we also identified a cluster of patients (137/1302, 10.5%) with an incident thromboembolism rate of 0.7%. Sensitivity analysis based on the survival decision tree approach selected a subgroup of patients with the same phenotypes as the metric-learning algorithm. CONCLUSIONS: Cluster analysis identified a distinct clinical phenotype at low risk of stroke among high-risk [CHA2 DS2 -VASc≥2 (3 for females)] patients with AF. The use of the novel analytic approach has the potential to prevent a subset of AF patients from unnecessary anticoagulation and avoid the associated risk of major bleeding.

Using multi-sourced big data to correlate sleep deprivation and road traffic noise: A US county-level ecological study.

BACKGROUND: Road traffic noise is a serious public health problem globally as it has adverse psychological and physiologic effects (i.e., sleep). Since previous studies mainly focused on individual levels, we aim to examine associations between road traffic noise and sleep deprivation on a large scale; namely, the US at county level. METHODS: Information from a large-scale sleep survey and national traffic noise map, both obtained from government's open data, were utilized and processed with Geographic Information System (GIS) techniques. To examine the associations between traffic noise and sleep deprivation, we used a hierarchical Bayesian spatial modelling framework to simultaneously adjust for multiple socioeconomic factors while accounting for spatial correlation. FINDINGS: With 62.90% of people not getting enough sleep, a 10 dBA increase in average sound-pressure level (SPL) or Ls10 (SPL of the relatively noisy area) in a county, was associated with a 49% (OR: 1.49; 95% CrIs:1.19-1.86) or 8% (1.08; 1.00-1.16) increase in the odds of a person in a particular county not getting enough sleep. No significant association was observed for Ls90 (SPL of the relatively quiet area). A 10% increase in noise exposure area or population ratio was associated with a 3% (1.03; 1.01-1.06) or 4% (1.04; 1.02-1.06) increase in the odds of a person within a county not getting enough sleep. INTERPRETATION: Traffic noise can contribute to variations in sleep deprivation among counties. This study suggests that policymakers could set up different noise-management strategies for relatively quiet and noisy areas and incorporate geospatial noise indicators, such as exposure population or area ratio. Furthermore, urban planners should consider urban sprawl patterns differently in terms of noise-induced sleep problems.

Nonhematogenic circulating aneuploid cells confer inferior prognosis and therapeutic resistance in gliomas.

Aneuploidy is the hallmark of malignancy. Our previous study successfully detected nonhematogenic circulating aneuploidy cells (CACs) in types of gliomas. The current prospective clinical study aims to further precisely subcategorize aneuploid CACs, including CD31- circulating tumor cells (CTCs) and CD31+ circulating tumor endothelial cells, and thoroughly investigate the clinical utilities of these different subtypes of cells. Co-detection and analysis of CTCs and circulating tumor-derived endothelial cells (CTECs) expressing CD133, glial fibrillary acidic protein (GFAP), or epidermal growth factor receptor variant III (EGFR vIII) were performed by integrated subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) in 111 preoperative primary diffuse glioma patients. Aneuploid CACs could be detected in most de novo glioma patients. Among detected CACs, 45.6% were CD31- /CD45- aneuploid CTCs and the remaining 54.4% were CD31+ /CD45- aneuploid CTECs. Positive detection of CTECs significantly correlated with disruption of the blood-brain barrier. The median number of large CTCs (L CTCs, >5 µm, 2) in low-grade glioma (WHO grade 2) was less than high-grade glioma (WHO grades 3 and 4) (3, p = 0.044), but this difference was not observed in small CTCs (S CTCs, ≤5 µm), CTECs or CACs (CTCs + CTECs). The numbers of CTCs, CTECs, or CACs in patients with contrast-enhancing (CE) lesions considerably exceeded that of non-CE lesions (p < 0.05). Receiver operating characteristic curves demonstrated that CD31+ CTECs, especially L CTECs, exhibited a close positive relationship with CE lesions. Survival analysis revealed that the high number of CD31- CTCs could be an adverse factor for compromised progression-free survival and overall survival. Longitudinal surveillance of CD31- CTCs was suitable for evaluating the therapeutic response and for monitoring potential emerging treatment resistance.

The Identification of Prognostic and Metastatic Alternative Splicing in Skin Cutaneous Melanoma.

Skin cutaneous melanoma (SKCM) is a type of highly invasive cancer originated from melanocytes. It is reported that aberrant alternative splicing (AS) plays an important role in the neoplasia and metastasis of many types of cancer. Therefore, we investigated whether ASEs of pre-RNA have such an influence on the prognosis of SKCM and the related mechanism of ASEs in SKCM. The RNA-seq data and ASEs data for SKCM patients were obtained from the TCGA and TCGASpliceSeq database. The univariate Cox regression revealed 1265 overall survival-related splicing events (OS-SEs). Screened by Lasso regression, 4 OS-SEs were identified and used to construct an effective prediction model (AUC: .904), whose risk score was proved to be an independent prognostic factor. Furthermore, Kruskal-Wallis test and Mann-Whitney-Wilcoxon test showed that an aberrant splicing type of aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2) regulated by CDC-like kinase 1 (CLK1) was associated with the metastasis and stage of SKCM. Besides, the overlapped signal pathway for AIMP2 was galactose metabolism identified by the co-expression analysis. External database validation also confirmed that AIMP2, CLK1, and the galactose metabolism were associated with the metastasis and stage of SKCM patients. ChIP-seq and ATAC-seq methods further confirmed the transcription regulation of CLK1, AIMP2, and other key genes, whose cellular expression was detected by Single Cell Sequencing. In conclusion, we proposed that CLK1-regulated AIMP2-78704-ES might play a critical role in the tumorigenesis and metastasis of SKCM via galactose metabolism. Besides, we established an effective model with MTMR14-63114-ES, URI1-48867-ES, BATF2-16724-AP, and MED22-88025-AP to predict the metastasis and prognosis of SKCM patients.

Combining hyperintense FLAIR rim and radiological features in identifying IDH mutant 1p/19q non-codeleted lower-grade glioma.

OBJECTIVES: Even very small residual tumors of IDH mutant 1p/19q non-codeleted (IDHmut-Noncodel) astrocytoma could have a significantly negative impact on survival; thus, accurate preoperative diagnosis is of utmost importance to guide aggressive tumor resection strategy for this subtype. This study aimed to diagnose IDHmut-Noncodel from IDH mutant 1p/19q codeleted (IDHmut-Codel) and IDH wild-type gliomas by preoperative MRI and CT to guide surgical plan-making. METHODS: Consecutive adult patients diagnosed with diffuse lower-grade glioma (LGG, histological grade 2-3) from December 1, 2013 to December 31, 2020, were retrospectively included in this study. Clinical and radiological features were recorded and analyzed. Patients were divided into cohort A and cohort B for training and validation based on the operation date (2:1). RESULTS: A total of 585 patients were included in this study (cohort A, 390; cohort B, 195). The hyperintense FLAIR rim with hypointense core (hyperFLAIRrim) was a more sensitive sign than T2-FLAIR mismatch (T2FM) in defining IDHmut-Noncodel astrocytoma (sensitivity in cohort A: 0.713, 0.539, respectively; in cohort B: 0.713, 0.489, respectively) without compromised specificity (all 1.00). The hyperFLAIRrim, higher rADC, homogenous pattern on T2WI, non-calcification, and younger age were the most important factors associated with IDHmut-Noncodel astrocytoma. Combining these factors, the random forest model showed the best predictive ability. CONCLUSION: The hyperFLAIRrim sign was a specific and more sensitive sign in diagnosing IDHmut-Noncodel astrocytoma. Combining hyperFLAIRrim, higher rADC, homogenous pattern, non-calcification, and younger age could precisely predict glioma subtype for subsequent surgical plan-making. KEY POINTS: • A single hyperintense FLAIR rim (hyperFLAIRrim) sign with a hypointense core, regardless of T2 appearance, was more sensitive than T2FM in diagnosing IDHmut-Noncodel astrocytoma with high specificity. • The higher rADC value, homogenous pattern on T2WI, non-calcification, and younger age have a close relationship with IDHmut-Noncodel astrocytoma. • Neurosurgeons should perform a more aggressive resection strategy to prolong survival for radiologically indicated IDHmut-Noncodel astrocytoma. Our study provided a usable, practicable, and reliable protocol for neurosurgeons to make an individualized surgical strategy.

Restoration of organic-matter-impoverished arable soils through the application of soil conditioner prepared via short-time hydrothermal fermentation.

The diversity and stability of critical microbial communities are of great importance for ensuring soil fertility. From the perspective of stimulating microbial diversity in organic-matter-impoverished arable soils, soil conditioner with a certain proportion of labile organic carbon was prepared by short-time hydrothermal fermentation (SHF). The effects of applying SHF, along with soil conditioner derived from traditional aerobic fermentation (TF) and heterogeneous fertilizer (HF), on soil texture, dissolved organic matter evolution, the structure of humic acid, and the succession of dominant microbial taxa were evaluated. SHF enhanced the storage capacity of soil organic carbon and nitrogen retention, and increased the relative abundance of Proteobacteria, Firmicutes and Nitrospirae in organic-matter-impoverished arable soil, with Lysobacter as its significant difference species. In conclusion, the proposed soil conditioner and the positive effects observed in this study indicate that it could be used to solve dual problems of food waste recycling and arable soil improvement.

A novel process for food waste recycling: A hydrophobic liquid mulching film preparation.

Appropriate and effective recycling of food waste (FW) has become increasingly significant with the promotion of garbage classification in China. In this study, a novel and green process was developed to recycle FW to prepare a biodegradable composite liquid mulching film (LMF) through crosslinking with sodium alginate (SA). The solid phase of FW was obtained as the raw material after hydrothermal pretreatment to remove pathogens and salts, and to improve the reactivity of active components at a moderate temperature. The prepared LMF had a hydrophobic surface and compact structure due to the lipid in FW and the acetalization reaction and hydrogen bonds among SA, glutaraldehyde and multi-active components of FW, resulting in enhanced water vapor barrier properties. The minimum water vapor permeability of the prepared LMF reached (8.23 ± 0.05) ✕ 10-12 g cm/(cm2·s·Pa) with 1.82 wt % of plasticizer, 0.74 wt% of crosslinker and a mass ratio of HTP-FW to SA of 3.56:1. The prepared LMF showed good mechanical properties and could maintain its integrity after spraying it on the soil surface for 31 days. In addition, it could effectively prevent the loss of soil moisture and heat, promote the seed germination of Chinese cabbage and achieve 89.14% of weight loss after burying in the soil for 27 days. This study provides a high value-added route to convert the FW to a hydrophobic LMF with superior properties, which addresses not only the problem of food waste but also the pollution of plastic mulching film.

Relationships between building attributes and COVID-19 infection in London.

In the UK, all domestic COVID-19 restrictions have been removed since they were introduced in March 2020. After illustrating the spatial-temporal variations in COVID-19 infection rates across London, this study then particularly aimed to examine the relationships of COVID-19 infection rates with building attributes, including building density, type, age, and use, since previous studies have shown that the built environment plays an important role in public health. Multisource data from national health services and the London Geomni map were processed with GIS techniques and statistically analysed. From March 2020 to April 2022, the infection rate of COVID-19 in London was 3,159.28 cases per 10,000 people. The spatial distribution across London was uneven, with a range from 1,837.88 to 4,391.79 per 10,000 people. During this period, it was revealed that building attributes played a significant role in COVID-19 infection. It was noted that higher building density areas had lower COVID-19 infection rates in London. Moreover, a higher percentage of historic or flat buildings tended to lead to a decrease in infection rates. In terms of building use, the rate of COVID-19 infection tended to be lower in public buildings and higher in residential buildings. Variations in the infection rate were more sensitive to building type; in particular, the percentage of residents living in flats contributed the most to variations in COVID-19 infection rates, with a value of 2.3%. This study is expected to provide support for policy and practice towards pandemic-resilient architectural design.

Combining MGMT promoter pyrosequencing and protein expression to optimize prognosis stratification in glioblastoma.

Pyrosequencing (PSQ) represents the golden standard for MGMT promoter status determination. Binary interpretation of results based on the threshold from the average of several CpGs tested would neglect the existence of the "gray zone". How to define the gray zone and reclassify patients in this subgroup remains to be elucidated. A consecutive cohort of 312 primary glioblastoma patients were enrolled. CpGs 74-81 in the promoter region of MGMT were tested by PSQ and the protein expression was assessed by immunohistochemistry (IHC). Receiver operating characteristic curves were constructed to calculate the area under the curves (AUC). Kaplan-Meier plots were used to estimate the survival rate of patients compared by the log-rank test. The optimal threshold of each individual CpG differed from 5% to 11%. Patients could be separated into the hypomethylated subgroup (all CpGs tested below the corresponding optimal thresholds, n = 126, 40.4%), hypermethylated subgroup (all CpGs tested above the corresponding optimal thresholds, n = 108, 34.6%), and the gray zone subgroup (remaining patients, n = 78, 25.0%). Patients in the gray zone harbored an intermediate prognosis. The IHC score instead of the average methylation levels could successfully predict the prognosis for the gray zone (AUC for overall survival, 0.653 and 0.519, respectively). Combining PSQ and IHC significantly improved the efficiency of survival prediction (AUC: 0.662, 0.648, and 0.720 for PSQ, IHC, and combined, respectively). Immunohistochemistry is a robust method to predict prognosis for patients in the gray zone defined by PSQ. Combining PSQ and IHC could significantly improve the predictive ability for clinical outcomes.

Ultrabroadband Entangled Photons on a Nanophotonic Chip.

The development of quantum technologies on nanophotonic platforms has seen momentous progress in the past decade. Despite that, a demonstration of time-frequency entanglement over a broad spectral width is still lacking. Here we present an efficient source of ultrabroadband entangled photon pairs on a periodically poled lithium niobate nanophotonic waveguide. Employing dispersion engineering, we demonstrate a record-high 100 THz (1.2 µm-2 µm) generation bandwidth with a high efficiency of 13 GHz/mW and excellent noise performance with the coincidence-to-accidental ratio exceeding 10^{5}. We also measure strong time-frequency entanglement with over 98% two-photon interference visibility.

Convex-Meniscus-Assisted Self-Assembly at the Air/Water Interface to Prepare a Wafer-Scale Colloidal Monolayer Without Overlap.

Self-assembly at the air/water interface (AWI) has proven to be an efficient strategy for fabricating two-dimensional (2D) colloidal monolayers, which was widely used as the template for nanosphere lithography in nanophononics, optofluidics, and solar cell studies. However, the monolayers fabricated at the AWI usually suffer from a small domain area and quasi-double layer structure caused by submerged particles. To overcome this, we proposed an improved protocol to prepare 2D colloidal monolayers free of overlapping nanospheres at the AWI. Utilizing the stable suspension infusion to the water surface, a convex meniscus, whose height is related to viscous force, was formed adjoining the three-phase boundary. As a result of the resistance of the convex meniscus, the polystyrene nanospheres in the initial suspension directly self-assembled into a preliminary monolayer, which proved effective in preventing nanospheres' sinking and increasing the colloidal crystal domain size. An optimal parameter for transferring the monolayer was also developed based on the numerical simulation results. Finally, a wafer-scale monolayer, covered with less than one nanosphere per 100 µm × 100 µm area, was achieved on the desired substrate with an average domain size attaining centimeter scale. The high-quality 2D colloidal crystal may further promote the application of nanosphere lithography, especially in the fields that require a defect-free template.

Microsphere mediated exosome isolation and ultra-sensitive detection on a dielectrophoresis integrated microfluidic device.

Tumor-derived exosomes have been recognized as potential biomarkers for cancer diagnosis because they are actively involved in cancer progression and metastasis. However, progress in practical exosome analysis is still slow due to the limitation in exosome isolation and detection. The development of microfluidic devices has provided a promising analytical platform compared with traditional methods. In this study, we develop an exosome isolation and detection method based on a microfluidic device (ExoDEP-chip), which realized microsphere mediated dielectrophoretic isolation and immunoaffinity detection. Exosomes were firstly isolated by binding to antibodies pre-immobilized on the polystyrene (PS) microsphere surface and were further detected using fluorescently labeled antibodies by fluorescence microscopy. Single microspheres were then trapped into single microwells under the DEP force in the ExoDEP-chip. A wide range from 1.4 × 103 to 1.4 × 108 exosomes per mL with a detection limit of 193 exosomes per mL was obtained. Through monitoring five proteins (CD81, CEA, EpCAM, CD147, and AFP) of exosomes from three different cell lines (A549, HEK293, and HepG2), a significant difference in marker expression levels was observed in different cell lines. Therefore, this method has good prospects in exosome-based tumor marker detection and cancer diagnosis.

Transcriptome profiling reveals differential expression of immune-related genes in gills of hybrid yellow catfish (Tachysurus fulvidraco ♀ × Pseudobagrus vachellii ♂) under hypoxic stress: Potential NLR-mediated immune response.

Fish gills are the primary organ that respond to sudden changes in the dissolved oxygen (DO) level in the aquatic environment. Hypoxic stress impairs the normal function of gill tissues. However, little is known about the mechanisms of the response of yellow catfish gills to hypoxic stress. In this study, we compared transcriptomic and physiological changes in gill tissues of hybrid yellow catfish (Tachysurus fulvidraco ♀ × Pseudobagrus vachellii ♂) between a hypoxia-treated group (DO: 1.5 mg/L) and a control group (DO: 6.5 mg/L). In fish in the hypoxia-treated group, gill filaments underwent adaptive changes, and the number of vacuoles in gill tissues increased. Exposure to hypoxic conditions for 96 h resulted in increased anaerobic metabolism and decreased antioxidant and immune capacity in gill tissues. Transcriptome analyses revealed 1556 differentially expressed genes, including 316 up-regulated and 1240 down-regulated genes, between fish in the hypoxia-treated and control groups. Functional analyses indicated that the main pathway enriched with differentially expressed genes was immune response, followed by energy metabolism and signal transduction. Under hypoxic stress, the transcript levels of genes involved in the NOD-like receptor signaling pathway initially increased rapidly but then decreased over time, suggesting that the NOD-like receptor-mediated immune response plays an essential role in hypoxia tolerance and resistance in hybrid yellow catfish. Our results provide novel insights into which immune-related genes and pathways are activated under hypoxic stress, and reveal details of early adaptation of the immune response and defense mechanisms under hypoxic stress.