Aesthetic Cellulose Filaments with Water-Triggered Switchable Internal Stress and Customizable Polarized Iridescence Toward Green Fashion Innovation.

Healthy, convenient, and aesthetic hair dyeing and styling are essential to fashion trends and personal-social interactions. Herein, we fabricate green, scalable, and aesthetic regenerated cellulose filaments (ACFs) with customizable iridescent colors, outstanding mechanical properties, and water-triggered moldability for convenient and fashionable artificial hairdressing. The fabrication of ACFs involves cellulose dissolution, cross-linking, wet-spinning, and nanostructured orientation. Notably, the cross-linking strategy endows the ACFs with significantly weakened internal stress, confirmed by monitoring the offset of the C-O-C group in the cellulose molecular chain with Raman imaging, which ensures a tailorable orientation of the nanostructure during wet stretching and tunable iridescent polarization colors. Interestingly, ACFs can be tailored for three-dimensional shaping through a facile water-triggered adjustable internal stress: temporary shaping with low-level internal stress in the wet state and permanent shaping with high-level internal stress in the dry state. The health, convenience, and green aesthetic filaments show great potential in personal wearables.

Identification of potential biomarkers and candidate therapeutic drugs for clear cell renal cell carcinoma by bioinformatic analysis and reverse network pharmacology.

This study aims to analyze the potential biomarkers using bioinformatics technology, explore the pathogenesis, and investigate potential Chinese herbal ingredients for the Clear cell renal cell carcinoma (ccRCC), which could provide theoretical basis for early diagnosis and effective treatment of ccRCC. The gene expression datasets GSE6344 and GSE53757 were obtained from the Gene Expression Omnibus database to screen differentially expressed genes (DEGs) involved in ccRCC carcinogenesis and disease progression. Enrichment analyses, protein-protein interaction networks construction, survival analysis and herbal medicines screening were performed with related software and online analysis platforms. Moreover, network pharmacology analysis has also been performed to screen potential target drugs of ccRCC and molecular docking analysis has been used to validate their effects. Total 274 common DEGs were extracted through above process, including 194 up-regulated genes and 80 down-regulated genes. The enrichment analysis revealed that DEGs were significantly focused on multiple amino acid metabolism and HIF signaling pathway. Ten hub genes, including FLT1, BDNF, LCP2, AGXT2, PLG, SLC13A3, SLC47A2, SLC22A8, SLC22A7, and SLC13A3, were screened. Survival analysis showed that FLT1, BDNF, AGXT2, PLG, SLC47A2, SLC22A8, and SLC12A3 were closely correlated with the overall survival of ccRCC, and AGXT2, SLC47A2, SLC22A8, and SLC22A7 were closely associated with DFS. The potential therapeutic herbs that have been screened were Danshen, Baiguo, Yinxing, Huangqin and Chuanshanlong. The active compounds which may be effective in ccRCC treatment were kaempferol, Scillaren A and (-)-epigallocatechin-3-gallate.

An ensemble deep learning model for risk stratification of invasive lung adenocarcinoma using thin-slice CT.

Lung cancer screening using computed tomography (CT) has increased the detection rate of small pulmonary nodules and early-stage lung adenocarcinoma. It would be clinically meaningful to accurate assessment of the nodule histology by CT scans with advanced deep learning algorithms. However, recent studies mainly focus on predicting benign and malignant nodules, lacking of model for the risk stratification of invasive adenocarcinoma. We propose an ensemble multi-view 3D convolutional neural network (EMV-3D-CNN) model to study the risk stratification of lung adenocarcinoma. We include 1075 lung nodules (≤30 mm and ≥4 mm) with preoperative thin-section CT scans and definite pathology confirmed by surgery. Our model achieves a state-of-art performance of 91.3% and 92.9% AUC for diagnosis of benign/malignant and pre-invasive/invasive nodules, respectively. Importantly, our model outperforms senior doctors in risk stratification of invasive adenocarcinoma with 77.6% accuracy [i.e., Grades 1, 2, 3]). It provides detailed predictive histological information for the surgical management of pulmonary nodules. Finally, for user-friendly access, the proposed model is implemented as a web-based system ( https://seeyourlung.com.cn ).

Glycyrrhizic acid glycosides reduces extensive tripterygium glycosides-induced lipid deposition in hepatocytes.

Aim: Tripterygium glycosides (TG) extracted from the plant Tripterygium wilfordii Hook F has been used to treat chronic kidney diseases for many years. However, hepatotoxicity limits its clinical application. Glycyrrhizic acid glycosides (GA) can reduce TG hepatotoxicity, however, further investigation into the underlying molecular mechanisms by which GA attenuates TG-induced hepatotoxicity is required. Methods: Sprague‒Dawley rats were randomly divided into the control group, the TG groups (TG189 mg/kg group, TG472.5 mg/kg group), and the TG + GA groups (TG189 mg/kg + GA20.25 mg/kg group, TG472.5 mg/kg + GA20.25 mg/kg group). After 21 consecutive days of intragastric administration, structural and molecular changes in hepatocytes were detected. Results: After 21 days of TG treatment, the serum level of the total bilirubin, triglyceride, total cholesterol, and low-density lipoprotein cholesterol increased in the TG189 mg/kg and TG472.5 mg/kg groups when compared to the control group. High-density lipoprotein cholesterol levels were reduced in both TG groups. The ultrastructure of hepatocytes and the structural integrity of the liver were compromised. In addition, the relevant molecular level of the peroxisome proliferators-activated receptor α (PPARα) and acyl-CoA synthetase long-chain family members (ACSLs) pathway was modulated. With the addition of 20.25 mg/kg GA, the serum biochemical indexes and liver tissue structure ultrastructure of hepatocytes were improved, and the PPARα-ACSLs pathway was corrected. Conclusion: The combined application of GA and TG improved abnormal lipid metabolism, repaired liver structure, reduced lipid deposition in hepatocytes, and reduced TG-induced hepatotoxicity.

Water and oil-resistant paper materials based on sodium alginate/hydroxypropyl methylcellulose/polyvinyl butyral/nano-silica with biodegradable and high barrier properties.

Despite many technical challenges in the development of safe and environmentally friendly food packaging paper materials with excellent water and oil resistance using simple methods, producing paper-based functional materials using bio-based polymers is currently an important topic in the food packaging industry. In this study, novel water and oil-resistant coatings for the paper were developed through the combination of sodium alginate (SA), hydroxypropyl methylcellulose (HPMC), polyvinyl butyral (PVB), and hydrophobic silica nanoparticles (HSNPs). To impart oil-repellency to paper, SA and HPMC were first mixed uniformly and coated on the base paper, which was pre-treated with calcium chloride solution. A compact and tough coating layer was formed on paper due to the hydrogen bonding between SA and HPMC molecules, and the crosslinking between SA and Ca2+ ions in the base paper. High water resistance of the paper was achieved through the coating of PVB and HSNPs on top of the coating of SA/HPMC. The final coated paper demonstrated outstanding oil resistance (kit rating: 12/12), water resistance (Cobb value: 4.23 g/m2), low water vapor transmission rate (100 g/m2·24 h), and improved mechanical properties. This fluorine-free, and biodegradable barrier paper will find excellent applications in the food packaging industry.

Hb Huadu [α124(H7)Ser→Thr (TCC>ACC), HBA2: c.373T>A]: A Novel Variant of the α-Globin Gene.

Here, we report a novel α chain hemoglobin (Hb) variant found during routine thalassemia screening. This Hb variant can be detected by capillary electrophoresis (CE) but cannot be recognized by high performance liquid chromatography (HPLC). Sanger sequencing revealed a heterozygous missense substitution at nucleotide 373 on the HBA2 gene, which results in the replacement of serine by threonine at codon 124 [α124(H7)Ser→Thr (TCC>ACC), HBA2: c.373T>A]. It is the first report of this variant, named Hb Huadu for the birthplace of the proband. In addition, the proband coinherited the heterozygous codons 41/42 (-TTCT) (HBB: c126_129delCTTT) on the ß-globin gene.

Discordance in Tumor Mutation Burden from Blood and Tissue Affects Association with Response to Immune Checkpoint Inhibition in Real-World Settings.

BACKGROUND: Tumor mutation burden (TMB), a biomarker for immune checkpoint inhibitor (CPI) response, is reported by both blood- and tissue-based next-generation sequencing (NGS) vendors. However, the agreement between TMB from blood (bTMB) and tissue (tTMB) in real-world settings, both in absolute value and association with CPI response, is not known. MATERIALS AND METHODS: This study utilizes Sarah Cannon's precision medicine platform, Genospace, to harmonize clinico-genomic data from 17 206 patients with cancer with NGS results from September 2015 to August 2021. A subset of patients have both bTMB and tTMB results. Statistical analyses are performed in R and include (1) correlation (r) and concordance (ρ) between patient-matched bTMB-tTMB pairs, (2) distribution of total bTMB and tTMB values, and (3) association of bTMB and tTMB with time to CPI therapy failure. RESULTS: In 410 patient-matched bTMB-tTMB pairs, the median bTMB (m = 10.5 mut/Mb) was significantly higher than the median tTMB (m = 6.0 mut/Mb, P < .001) leading to conflicting "high" and "low" statuses in over one-third of cases at a threshold of 10 mut/Mb (n = 410). Significant differences were observed in the distribution of bTMB values from blood-NGS vendors, with guardant health (GH) reporting higher (m = 10.5 mut/Mb, n = 2183) than Foundation Medicine (FMI, m = 3.8 mut/Mb, n = 462, P < .001). bTMB from GH required a higher threshold (≥40 mut/Mb) than bTMB from FMI (≥12 mut/Mb) in order to be associated with CPI response. CONCLUSIONS: This study uncovers variability in bTMB reporting among commercial NGS platforms, thereby evidencing a need for assay-specific thresholds in identifying patients who may respond to CPI therapy.

Piezoresistive Conductive Microfluidic Membranes for Low-Cost On-Chip Pressure and Flow Sensing.

Over the last two decades, the field of microfluidics has received significant attention from both academia and industry. Each year, researchers report thousands of new prototype devices for use in a broad range of environmental, pharmaceutical, and biomedical engineering applications. While lab-on-a-chip fabrication costs have continued to decrease, the hardware required for monitoring fluid flows within the microfluidic devices themselves remains expensive and often cost-prohibitive for researchers interested in starting a microfluidics project. As microfluidic devices become capable of handling complex fluidic systems, low-cost, precise, and real-time pressure and flow rate measurement capabilities have become increasingly important. While many labs use commercial platforms and sensors, these solutions can often cost thousands of dollars and can be too bulky for on-chip use. Here we present a new inexpensive and easy-to-use piezoresistive pressure and flow sensor that can be easily integrated into existing on-chip microfluidic channels. The sensor consists of PDMS-carbon black conductive membranes and uses an impedance analyzer to measure impedance changes due to fluid pressure. The sensor costs several orders of magnitude less than existing commercial platforms and can monitor local fluid pressures and calculate flow rates based on the pressure gradient.

Leveraging high-throughput purification to accelerate viral vector process development.

Recombinant adeno-associated virus (AAV) has been broadly used as a delivery tool for gene therapy applications. The development of a robust purification process is essential for delivering high purity and quality AAV products to clinic. The short clinical timelines and material limitations of early-stage development pose unique challenges to developing robust and scalable downstream purification processes. One approach to overcome these limitations is to leverage high throughput (HTP) strategies and automation technologies for purification process development, an approach that is well established in protein biologics and other areas. However, due to the unique challenges related to viral vector purification, implementing HTP approaches for gene therapy process development has not been explored extensively. In this paper, we established a HTP chromatography platform and demonstrated its capability to facilitate gene therapy purification process development using both mini-columns and self-packed resin plates. The end-to-end development workflow for AAV HTP purification is detailed in this work with the expectation of serving as an introductory for the AAV purification development field. Comparable process performance was confirmed between a bench-scale chromatography process and an HTP chromatography format. Slightly lower recovery was observed using the HTP format (62% vs 75%), as well as %full capsid enrichment (71% vs. 82%). Comparable impurity clearance capability was demonstrated between the two different systems as well. It was concluded that the established HTP chromatography formats can serve as a surrogate to bench-scale chromatography development to reduce material needs and development timelines for AAV purification development.

Chiral Cellulose Nanocrystal Humidity-Responsive Iridescent Films with Glucan for Tuned Iridescence and Reinforced Mechanics.

The fabrication of biomimetic photonic materials with environmental stimuli-responsive functions from entirely biobased materials is becoming increasingly challenging with the growing demand for biodegradable materials. Herein, the effect of glucan with different molecular weights on the mechanical performance and tunable structural color of iridescent CNC composite films was investigated. The existence of glucan did not influence the self-assembly performance of CNCs, but rather led to an improvement in the mechanical performance, enabling cholesteric CNC composite films with an adjustable structural color. Simultaneously, the iridescent films showed a conspicuous redshift and enlarged initial pitch without obstruction of the chiral structure. In response to environmental humidity, the structural colors of the iridescent composite films can be changed by regulating their chiral nematic structure. In particular, the films demonstrate a reversible structural color change between blue and red at RH between 50 and 98%. The resulting biobased iridescent composite films have potential applications in decorative coating, optical and humidity sensing, and anticounterfeiting.

Efficient homogeneous TEMPO-mediated oxidation of cellulose in lithium bromide hydrates.

An appropriate cellulose-dissolving solvent is critical for the homogeneous oxidation of cellulose using TEMPO (2, 2, 6, 6-tetramethylpiperidine-1-oxyl)-mediated system. Herein, TEMPO/NaClO/NaClO2 system in lithium bromide hydrates (LBHs) was developed for the homogeneous selective-oxidation of cellulose, which was two-stage protocol involving cellulose dissolution and homogeneous oxidation. Specifically, cellulose was firstly dissolved in LiBr·3.5H2O and offered the optimal pH (5.6) for the subsequent TEMPO/NaClO/NaClO2 oxidation without precipitation of the cellulose chains. Effect of reaction conditions on cellulose oxidation was investigated. The results showed that high degree of oxidation (DO) and evenly distributed carboxyl could be achieved. The particle size gradually decreased with DO, and oxidized cellulose with high water solubility and amorphous structure could be obtained. Furthermore, FT-IR, 13C NMR and fractionation analysis verified that cellulose was successfully converted and the carboxyl uniformly distributed onto the cellulose chains. This TEMPO-mediated system using LBHs as solvent presented an efficient method on the homogeneous selective oxidation of primary hydroxyl in cellulose.

Tumor-Specific and Tumor-Agnostic Molecular Signatures Associated With Response to Immune Checkpoint Inhibitors.

PURPOSE: Next-generation sequencing (NGS) testing is being incorporated into routine standard of care for patients with cancer. Immune checkpoint inhibitors (CPIs) are approved for use in both tumor-specific and tumor-agnostic indications. We sought to determine tumor type-specific or tumor-agnostic correlations between mutations detected by NGS and response to CPIs. MATERIALS AND METHODS: A retrospective analysis of 26,004 patient records with NGS data available was conducted. Time to treatment failure and overall survival analyses were performed. Hazard ratios and associated statistics were computed in the R programming language. The study was considered exempt from internal review board review and data were considered nonhuman subjects. RESULTS: Response to CPIs varied between tumor types with melanoma and lung cancer performing relatively better on CPIs than other tumor types. Within tumor types, response to CPIs was stratified by mutations in specific genes. Tumor-agnostic markers including high tumor mutation burden and microsatellite instability-high were also associated with longer time to treatment failure on CPIs. Importantly, within the high tumor mutation burden and microsatellite instability-high groups, mutations in individual genes correlate with response to CPIs. CONCLUSION: The results from commercial NGS panels may be used to stratify patients for response to CPIs. In tumors where CPIs show relatively low efficacy, there may be distinct patient populations-based on gene mutation status-that are predicted to have better response to CPIs. Likewise, there may be distinct patient populations who do relatively worse on CPIs within tumor types known to respond well to CPIs.

Analytical Strategies for Quantification of Adeno-Associated Virus Empty Capsids to Support Process Development.

Recombinant adeno-associated virus (rAAV)-mediated gene therapy is a fast-evolving field in the biotechnology industry. One of the major challenges in developing a purification process for AAV gene therapy is establishing an effective yet scalable method to remove empty capsids, or viral vectors lacking the therapeutic gene, from full capsids-viral product containing the therapeutic sequence. Several analytical methods that can quantify the empty-to-full capsid ratio have been reported in the literature. However, as samples can vary widely in viral titer, buffer matrix, and the relative level of empty capsids, understanding the specifications and limitations of different analytical methods is critical to providing appropriate support to facilitate process development. In this study, we developed a novel anion-exchange high-performance liquid chromatography assay to determine the empty-to-full capsid ratio of rAAV samples. The newly developed method demonstrated good comparability with both the transmission electron microscopy and analytical ultracentrifugation methods used in empty-to-full capsid ratio quantification, while providing much higher assay throughput and reducing the minimum sample concentration requirement to 2.7E11 viral genomes/mL.

Microfluidic device for primary tumor spheroid isolation.

BACKGROUND: Traditional two-dimensional (2-D) monolayer cell culture is vastly different from in vivo physiological conditions, which can lead to inaccurate or insufficient data in areas where response and efficacy within humans are being investigated, such as drug discovery, pathology studies, etc. Misleading results arise from two main disadvantages of monolayer cell culture. First, after several passages, cell lines lose many features from their original in vivo state. Second, the morphology of cells cultured in a monolayer is much different from the cell morphology in three-dimensional (3-D) in vivo conditions, thus resulting in altered cellular function. Three-dimensional multi-cellular spheroids, on the other hand, are a better representation of in vivo physiological conditions while still retaining many of the in vitro cell culture advantages. Primary spheroids freshly isolated from tissue samples are especially ideal for cell-based assays by avoiding the two problems of 2-D monolayer cell culture. METHODS: In this paper, we report a microfluidic device for primary tumor spheroid isolation. Pancreatic tumor samples from mice were used in the experiments. RESULTS: We successfully isolated primary tumor spheroids from the pancreatic tumor samples and were able to maintain the spheroids in culture for up to two weeks. CONCLUSIONS: This novel microfluidic device may promote and advance the isolation of primary tumor spheroids for future drug testing and interrogation of tumor characteristics.

Microfluidic free-flow zone electrophoresis and isotachophoresis using carbon black nano-composite PDMS sidewall membranes.

We present a new type of free-flow electrophoresis (FFE) device for performing on-chip microfluidic isotachophoresis and zone electrophoresis. FFE is performed using metal gallium electrodes, which are isolated from a main microfluidic flow channel using thin micron-scale polydimethylsiloxane/carbon black (PDMS/CB) composite membranes integrated directly into the sidewalls of the microfluidic channel. The thin membrane allows for field penetration and effective electrophoresis, but serves to prevent bubble generation at the electrodes from electrolysis. We experimentally demonstrate the ability to use this platform to perform on-chip free-flow electrophoretic separation and isotachophoretic concentration. Due to the small size and simple fabrication procedure, this PDMS/CB platform could be used as a part of an on-chip upstream sample preparation toolkit for portable microfluidic diagnostic applications.

Microfluidics made easy: A robust low-cost constant pressure flow controller for engineers and cell biologists.

Over the last decade, microfluidics has become increasingly popular in biology and bioengineering. While lab-on-a-chip fabrication costs have continued to decrease, the hardware required for delivering controllable fluid flows to the microfluidic devices themselves remains expensive and often cost prohibitive for researchers interested in starting a microfluidics project. Typically, microfluidic experiments require precise and tunable flow rates from a system that is simple to operate. While many labs use commercial platforms or syringe pumps, these solutions can cost thousands of dollars and can be cost prohibitive. Here, we present an inexpensive and easy-to-use constant pressure system for delivering flows to microfluidic devices. The controller costs less than half the price of a single syringe pump but can independently switch and deliver fluid through up to four separate fluidic inlets at known flow rates with significantly faster fluid response times. It is constructed of readily available pressure regulators, gauges, plastic connectors and adapters, and tubing. Flow rate is easily predicted and calibrated using hydraulic circuit analysis and capillary tubing resistors. Finally, we demonstrate the capabilities of the flow system by performing well-known microfluidic experiments for chemical gradient generation and emulsion droplet production.

Microfluidic Mixing and Analog On-Chip Concentration Control Using Fluidic Dielectrophoresis.

Microfluidic platforms capable of complex on-chip processing and liquid handling enable a wide variety of sensing, cellular, and material-related applications across a spectrum of disciplines in engineering and biology. However, there is a general lack of available active microscale mixing methods capable of dynamically controlling on-chip solute concentrations in real-time. Hence, multiple microfluidic fluid handling steps are often needed for applications that require buffers at varying on-chip concentrations. Here, we present a novel electrokinetic method for actively mixing laminar fluids and controlling on-chip concentrations in microfluidic channels using fluidic dielectrophoresis. Using a microfluidic channel junction, we co-flow three electrolyte streams side-by-side so that two outer conductive streams enclose a low conductive central stream. The tri-laminar flow is driven through an array of electrodes where the outer streams are electrokinetically deflected and forced to mix with the central flow field. This newly mixed central flow is then sent continuously downstream to serve as a concentration boundary condition for a microfluidic gradient chamber. We demonstrate that by actively mixing the upstream fluids, a variable concentration gradient can be formed dynamically downstream with single a fixed inlet concentration. This novel mixing approach offers a useful method for producing variable on-chip concentrations from a single inlet source.

Contactless microfluidic pumping using microchannel-integrated carbon black composite membranes.

The ability to pump and manipulate fluid at the micron-scale is a basic requirement for microfluidic platforms. Many current manipulation methods, however, require expensive and bulky external supporting equipment, which are not typically compatible for portable applications. We have developed a contactless metal electro-osmotic micropump capable of pumping conductive buffers. The pump operates using two pairs of gallium metal electrodes, which are activated using an external voltage source and separated from a main flow channel by a thin micron-scale polydimethylsiloxane (PDMS) membrane. The thin contactless membrane allows for field penetration and electro-osmotic flow within the microchannel, but eliminates electrode damage and sample contamination commonly associated with traditional DC electro-osmotic pumps that utilize electrodes in direct contact with the working fluid. Our previous work has demonstrated the effectiveness of this method in pumping deionized water. However, due to the high resistivity of PDMS, this method proved difficult to apply towards manipulating conductive buffers. To overcome this limitation, we fabricated conductive carbon black (CB) powder directly into the contactless PDMS membranes. The increased electrical conductivity of the contactless PDMS membrane significantly increased micropump performance. Using a microfluidic T-channel device and an electro-osmotic flow model, we determined the influence that CB has on pump pressure for CB weight percents varying between 0 and 20. The results demonstrate that the CB increases pump pressure by two orders of magnitude and enables effective operations with conductive buffers.

Correction: Microfluidic pumping, routing and metering by contactless metal-based electro-osmosis.

Correction for 'Microfluidic pumping, routing and metering by contactless metal-based electro-osmosis' by Xiaotong Fu et al., Lab Chip, 2015, DOI: 10.1039/c5lc00504c.

Microfluidic pumping, routing and metering by contactless metal-based electro-osmosis.

Over the past decade, many microfluidic platforms for fluid processing have been developed in order to perform on-chip fluidic manipulations. Many of these methods, however, require expensive and bulky external supporting equipment, which are not typically applicable for microsystems requiring portability. We have developed a new type of portable contactless metal electro-osmotic micropump capable of on-chip fluid pumping, routing and metering. The pump operates using two pairs of gallium metal electrodes, which are activated using an external voltage source, and separated from a main flow channel by a thin micron-scale PDMS membrane. The thin contactless membrane allows for field penetration and electro-osmotic (EO) flow within the microchannel, but eliminates electrode damage and sample contamination commonly associated with traditional DC electro-osmotic pumps that utilize electrodes in direct contact with the working fluid. The maximum flow rates and pressures generated by the pump using DI water as a working buffer are 10 nL min(-1) and 30 Pa, respectively. With our current design, the maximum operational conductivity where fluid flow is observed is 0.1 mS cm(-1). Due to the small size and simple fabrication procedure, multiple micropump units can be integrated into a single microfluidic device for automated on-chip routing and sample metering applications. We experimentally demonstrated the ability to quantify micropump electro-osmotic flowrate and pressure as a function of applied voltage, and developed a mathematical model capable of predicting the performance of a contactless micropump for a given external load and internal hydrodynamic microchannel resistance. Finally, we showed that by activating specific pumps within a microchannel network, our micropumps are capable of routing microchannel fluid flow and generating plugs of solute.