CircTLK1: A novel regulator involved in VSMC phenotypic switching and the developmental process of atherosclerosis.

Phenotypic switching of vascular smooth muscle cells (VSMCs) is essential for atherosclerosis development. Circular RNA (circRNA) is a specific non-coding RNA that is produced as a closed-loop structure in mammals, and its specific expression pattern is closely related to its cell type and tissue. To clarify the roles of circTLK1 in VSMC phenotypic switching, we performed qRT-PCR, immunoblotting, and immunostaining. qRT-PCR revealed that circTLK1 was upregulated in both mouse models of atherosclerosis in vivo and PDGF (platelet-derived growth factor)-BB-induced VSMCs in vitro. Furthermore, the overexpression of circTLK1 promoted PDGF-BB-induced VSMC phenotypic switching. Conversely, experiments performed in vivo demonstrate that the knockdown of SMC-specific circTLK1 led to a reduction in the development of atherosclerosis. The relationship between circTLK1 and miR-513a-3p and Krüppel-like factor 4 (KLF4) was detected by RNA immunoprecipitation (RIP), luciferase reporter assay, RNA pull-down, and RNA fluorescence in situ hybridization (RNA FISH). Mechanistically, circTLK1 acted as a sponge for miR-513a-3p, leading to the upregulation of KLF4, a key transcription factor for phenotypic switching. Targeting the circTLK1/miR-513a-3p/KLF4 axis may provide a potential therapeutic strategy for atherosclerosis.

Effect of novel anti-tumor and anti-angiogenesis drug taurolactone on angiogenic factor AGGF1 and angiogenesis mimicry in patients with hepatocellular carcinoma.

OBJECTIVE: Our study was to investigate the impact of taurolactone, a novel anti-tumor and anti-angiogenic drug, on AGGF1, an angiogenic factor, and angiogenesis mimicry in patients diagnosed with hepatocellular carcinoma (HCC). METHODS: A total of 120 HCC patients were enrolled from the Department of Oncology and Hepatobiliary Surgery at our hospital between May 2021 and December 2022. HCC diagnoses were confirmed through imaging or tissue biopsy for all patients. The age of patients ranged from 37 to 72 years, with an average age of 64.29 ± 4.58 years. These participants were divided equally into two groups: the control group and the observation group, each consisting of 60 individuals. While the control group received standard drug treatment, the observation group was administered taurolactone treatment. Before being included in the study, all participants or their legal representatives provided signed informed consent. Patient demographic information was collected through a questionnaire survey. ELISA was used to measure the levels of VEGF and AGGF1 in patients following treatment. Western blot was applied to assess the protein expression of PDGF, Angiopoietin, and AGGF1. MRI imaging technology was utilized to assess the perfusion characteristics of tumor blood vessels in patients. Tumor vessel density was compared between patients using ultrasonography. We also conducted a comparison between the two groups in terms of progression-free survival and overall survival. RESULTS: General patient information between the two groups showed no significant differences (P > 0.05). Of note, the observation group exhibited greatly lower levels of VEGF and AGGF1 compared to the control group (P < 0.05). Moreover, the levels of PDGF, Angiopoietin, and AGGF1 protein expression were significantly reduced in the observation group compared to the control group (P < 0.05). In terms of tumor perfusion, the observation group displayed lower average and maximum perfusion volumes in tumor blood vessels compared to the control group (P < 0.05). Additionally, the observation group demonstrated delayed peak times and arrival times of tumor blood vessels in comparison to the control group (P < 0.05). Furthermore, the density of tumor blood vessels was notably lower in the observation group compared to the control group (P < 0.05). Patients in the observation group had longer progression-free survival and overall survival than the control group (P < 0.05). CONCLUSION: In HCC patients, our study highlighted the potential efficacy of taurolactone treatment as it effectively inhibited angiogenic factors and angiogenesis mimicry, ultimately leading to an improved prognosis for these patients.

Fabrication of lidocaine-loaded polymer dissolving microneedles for rapid and prolonged local anesthesia.

There is an urgent need for research into effective interventions for pain management to improve patients' life quality. Traditional needle and syringe injection were used to administer the local anesthesia. However, it causes various discomforts, ranging from brief stings to trypanophobia and denial of medical operations. In this study, a dissolving microneedles (MNs) system made of composite matrix materials of polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), and sodium hyaluronate (HA) was successfully developed for the loading of lidocaine hydrochloride (LidH). The morphology, size and mechanical properties of the MNs were also investigated. After the insertion of MNs into the skin, the matrix at the tip of the MNs was swelled and dissolved by absorption of interstitial fluid, leading to a rapid release of loaded LidH from MNs' tips. And the LidH in the back patching was diffused into deeper skin tissue through microchannels created by MNs insertion, forming a prolonged anesthesia effect. In addition, the back patching of MNs could be acted as a drug reservoir to form a prolonged local anesthesia effect. The results showed that LidH MNs provided a superior analgesia up to 8 h, exhibiting a rapid and long-lasting analgesic effects. Additionally, tissue sectioning and in vitro cytotoxicity tests indicated that the MNs patch we developed had a favorable biosafety profile.

TREM2 promotes cholesterol uptake and foam cell formation in atherosclerosis.

Disordered lipid accumulation in the arterial wall is a hallmark of atherosclerosis. Previous studies found that the expression of triggering receptor expressed on myeloid cells 2 (TREM2), a transmembrane receptor of the immunoglobulin family, is increased in mouse atherosclerotic aortic plaques. However, it remains unknown whether TREM2 plays a role in atherosclerosis. Here we investigated the role of TREM2 in atherosclerosis using ApoE knockout (ApoE-/-) mouse models, primary vascular smooth muscle cells (SMCs), and bone marrow-derived macrophages (BMDMs). In ApoE-/- mice, the density of TREM2-positive foam cells in aortic plaques increased in a time-dependent manner after the mice were fed a high-fat diet (HFD). Compared with ApoE-/- mice, the Trem2-/-/ApoE-/- double-knockout mice showed significantly reduced atherosclerotic lesion size, foam cell number, and lipid burden degree in plaques after HFD feeding. Overexpression of TREM2 in cultured vascular SMCs and macrophages exacerbates lipid influx and foam cell formation by upregulating the expression of the scavenger receptor CD36. Mechanistically, TREM2 inhibits the phosphorylation of p38 mitogen-activated protein kinase and peroxisome proliferator activated-receptor gamma (PPARγ), thereby increasing PPARγ nuclear transcriptional activity and subsequently promoting the transcription of CD36. Our results indicate that TREM2 exacerbates atherosclerosis development by promoting SMC- and macrophage-derived foam cell formation by regulating scavenger receptor CD36 expression. Thus, TREM2 may act as a novel therapeutic target for the treatment of atherosclerosis.

Study on quality analysis of different species of Coptidis rhizome based on fingerprint-effect relationship.

INTRODUCTION: The quality evaluation of Coptidis rhizome (CR) is attributed to the origin and processing method, and this strategy of ignoring the bioactive components usually leads to biased quality analysis, which is difficult to indicate the clinical efficacy. OBJECTIVES: In order to evaluate the quality level of different species of CR, we collected 20 batches of CR and investigated the fingerprint-effect relationship. METHODS: High-performance liquid chromatography (HPLC) fingerprints of CR were established, and the fingerprint-effect relationship was explored using cluster analysis, principal component analysis, Pearson correlation analysis, grey relation analysis, and partial least squares regression. RESULTS: We have identified a total of 10 common peaks (1-10) with similarity scores above 0.96. The study on the relationship between spectra and potency further showed that the contents of peaks 8, 9, and 10 are potential key components. And based on a previous study, a method of one measurement and multiple evaluations of CR was established to achieve the goal of simplifying the analytical process and reducing costs. CONCLUSION: Through a combination of fingerprint analysis, antioxidant activity evaluation, fingerprint-efficacy relationship analysis, and simultaneous quantification of multiple components, a CR quality control index and method have been selected and established, which can also provide a more comprehensive quality evaluation for traditional Chinese medicine.

Targeting glutaminase is therapeutically effective in ibrutinib-resistant mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an incurable B-cell non-Hodgkin lymphoma characterized by frequent relapses. The development of resistance to ibrutinib therapy remains a major challenge in MCL. We previously showed that glutaminolysis is associated with resistance to ibrutinib. In this study, we confirmed that glutaminase (GLS), the first enzyme in glutaminolysis, is overexpressed in ibrutinib-resistant MCL cells, and that its expression correlates well with elevated glutamine dependency and glutaminolysis. Furthermore, we discovered that GLS expression correlates with MYC expression and the functioning of the glutamine transporter ASCT2. Depletion of glutamine or GLS significantly reduced cell growth, while GLS overexpression enhanced glutamine dependency and ibrutinib resistance. Consistent with this, GLS inhibition by its specific inhibitor telaglenastat suppressed MCL cell growth both in vitro and in vivo. Moreover, telaglenastat showed anti-MCL synergy when combined with ibrutinib or venetoclax in vitro, which was confirmed using an MCL patient-derived xenograft model. Our study provides the first evidence that targeting GLS with telaglenastat, alone or in combination with ibrutinib or venetoclax, is a promising strategy to overcome ibrutinib resistance in MCL.

DCBLD2 regulates vascular hyperplasia by modulating the platelet derived growth factor receptor-ß endocytosis through Caveolin-1 in vascular smooth muscle cells.

DCBLD2 is a neuropilin-like transmembrane protein that is up-regulated during arterial remodeling in humans, rats, and mice. Activation of PDGFR-ß via PDGF triggers receptor phosphorylation and endocytosis. Subsequent activation of downstream signals leads to the stimulation of phenotypic conversion of VSMCs and arterial wall proliferation, which are common pathological changes in vascular remodeling diseases such as atherosclerosis, hypertension, and restenosis after angioplasty. In this study, we hypothesized that DCBLD2 regulates neointimal hyperplasia through the regulation of PDGFR-ß endocytosis of vascular smooth muscle cells (VSMCs) through Caveolin-1 (Cav-1). Compared with wild-type (WT) mice or control littermate mice, the germline or VSMC conditional deletion of the Dcbld2 gene resulted in a significant increase in the thickness of the tunica media in the carotid artery ligation. To elucidate the underlying molecular mechanisms, VSMCs were isolated from the aorta of WT or Dcbld2-/- mice and were stimulated with PDGF. Western blotting assays demonstrated that Dcbld2 deletion increased the PDGF signaling pathway. Biotin labeling test and membrane-cytosol separation test showed that after DCBLD2 was knocked down or knocked out, the level of PDGFR-ß on the cell membrane was significantly reduced, while the amount of PDGFR-ß in the cytoplasm increased. Co-immunoprecipitation experiments showed that after DCBLD2 gene knock-out, the binding of PDGFR-ß and Cav-1 in the cytoplasm significantly increased. Double immunofluorescence staining showed that PDGFR-ß accumulated Cav-1/lysosomes earlier than for control cells, which indicated that DCBLD2 gene knock-down or deletion accelerated the endocytosis of PDGF-induced PDGFR-ß in VSMCs. In order to confirm that DCBLD2 affects the relationship between Cav-1 and PDGFR-ß, proteins extracted from VSMCs cultured in vitro were derived from WT and Dcbld2-/- mice, whereas co-immunoprecipitation suggested that the combination of DCBLD2 and Cav-1 reduced the bond between Cav-1 and PDGFR-ß, and DCBLD2 knock-out was able to enhance the interaction between Cav-1 and PDGFR-ß. Therefore, the current results suggest that DCBLD2 may inhibit the caveolae-dependent endocytosis of PDGFR-ß by anchoring the receptor on the cell membrane. Based on its ability to regulate the activity of PDGFR-ß, DCBLD2 may be a novel therapeutic target for the treatment of cardiovascular diseases.

Protein by-products: Composition, extraction, and biomedical applications.

Significant upsurge in animal by-products such as skin, bones, wool, hides, feathers, and fats has become a global challenge and, if not properly disposed of, can spread contamination and viral diseases. Animal by-products are rich in proteins, which can be used as nutritional, pharmacologically functional ingredients, and biomedical materials. Therefore, recycling these abundant and renewable by-products and extracting high value-added components from them is a sustainable approach to reclaim animal by-products while addressing scarce landfill resources. This article appraises the most recent studies conducted in the last five years on animal-derived proteins' separation and biomedical application. The effort encompasses an introduction about the composition, an overview of the extraction and purification methods, and the broad range of biomedical applications of these ensuing proteins.

Elastic priors to dynamically borrow information from historical data in clinical trials.

Use of historical data and real-world evidence holds great potential to improve the efficiency of clinical trials. One major challenge is to effectively borrow information from historical data while maintaining a reasonable type I error and minimal bias. We propose the elastic prior approach to address this challenge. Unlike existing approaches, this approach proactively controls the behavior of information borrowing and type I errors by incorporating a well-known concept of clinically significant difference through an elastic function, defined as a monotonic function of a congruence measure between historical data and trial data. The elastic function is constructed to satisfy a set of prespecified criteria such that the resulting prior will strongly borrow information when historical and trial data are congruent, but refrain from information borrowing when historical and trial data are incongruent. The elastic prior approach has a desirable property of being information borrowing consistent, that is, asymptotically controls type I error at the nominal value, no matter that historical data are congruent or not to the trial data. Our simulation study that evaluates the finite sample characteristic confirms that, compared to existing methods, the elastic prior has better type I error control and yields competitive or higher power. The proposed approach is applicable to binary, continuous, and survival endpoints.

SAM: Self-adapting mixture prior to dynamically borrow information from historical data in clinical trials.

Mixture priors provide an intuitive way to incorporate historical data while accounting for potential prior-data conflict by combining an informative prior with a noninformative prior. However, prespecifying the mixing weight for each component remains a crucial challenge. Ideally, the mixing weight should reflect the degree of prior-data conflict, which is often unknown beforehand, posing a significant obstacle to the application and acceptance of mixture priors. To address this challenge, we introduce self-adapting mixture (SAM) priors that determine the mixing weight using likelihood ratio test statistics or Bayes factors. SAM priors are data-driven and self-adapting, favoring the informative (noninformative) prior component when there is little (substantial) evidence of prior-data conflict. Consequently, SAM priors achieve dynamic information borrowing. We demonstrate that SAM priors exhibit desirable properties in both finite and large samples and achieve information-borrowing consistency. Moreover, SAM priors are easy to compute, data-driven, and calibration-free, mitigating the risk of data dredging. Numerical studies show that SAM priors outperform existing methods in adopting prior-data conflicts effectively. We developed R package "SAMprior" and web application that are freely available at CRAN and www.trialdesign.org to facilitate the use of SAM priors.

Antidiabetic activity of eupafolin through peroxisome proliferator-activated receptor-gamma and PI3K/Akt signaling in Type 2 diabetic rats.

Eupafolin is a phyto compound of flavone that exerts anti-inflammatory, antioxidant, and antiproliferative properties. The main purpose of this study is to examine the antidiabetic effect of eupafolin on nicotinamide-streptozotocin (STZ)-induced Type 2 diabetes (T2D) rats. After nicotinamide (120 mg/kg) treatment, STZ (60 mg/kg) was administrated intravenously to induce T2D. Rats with fasting blood glucose (FBG) > 200 mg/dL are chosen for the study 7 days after T2D induction. The eupafolin treatment was continued for another 15 days. FBG and an oral glucose tolerance test (OGTT) were measured on the 21st day after T2D induction. The blood lipid, serum insulin, and homeostatic model assessment (HOMA-IR) were determined. In liver homogenate, oxidative stress indicators were measured. In addition, the effect of eupafolin on the expression of the proteins InsR, insulin receptor substrate (IRS)-2, GLUT4, PPARγ, and phosphatidylinositol 3-kinase (PI3K)/Akt was investigated using a western blot. As measured by OGTT and HOMA-IR, eupafolin treatment reduced FBG and insulin resistance (IR). Furthermore, when compared to diabetic rats, liver antioxidant enzymes were dramatically normalized. The level of glycogen in the liver of diabetic rats was increased by eupafolin treatment. In T2D rats, eupafolin dramatically increased the InsR, IRS-2, GLUT4, and PPARγ. Further, the eupafolin treatment activated the PI3K/Akt signaling in T2D rats. These findings imply that the antidiabetic mechanism of eupafolin may be related to the activation of the PPARγ and the PI3K/Akt signaling pathway in T2D rats. As a result, the flavonoid eupafolin could be an antidiabetic medication for T2D after a comprehensive clinical investigation.

Neobavaisoflavone Inhibits Biofilm Formation and α-Toxin Activity of Staphylococcus aureus.

Neobavaisoflavone had antimicrobial activities against Gram-positive multidrug-resistant (MDR) bacteria, but the effect of neobavaisoflavone on the virulence and biofilm formation of S. aureus has not been explored. The present study aimed to investigate the possible inhibitory effect of neobavaisoflavone on the biofilm formation and α-toxin activity of S. aureus. Neobavaisoflavone presented strong inhibitory effect on the biofilm formation and α-toxin activity of both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains at 25 µM, but did not affect the growth of S. aureus planktonic cells. Genetic mutations were identified in four coding genes, including cell wall metabolism sensor histidine kinase walK, RNA polymerase sigma factor rpoD, tetR family transcriptional regulator, and a hypothetical protein. The mutation of WalK (K570E) protein was identified and verified in all the neobavaisoflavone-induced mutant S. aureus isolates. The ASN501, LYS504, ILE544 and GLY565 of WalK protein act as hydrogen acceptors to form four hydrogen bonds with neobavaisoflavone by molecular docking analysis, and TRY505 of WalK protein contact with neobavaisoflavone to form a pi-H bond. In conclusion, neobavaisoflavone had excellent inhibitory effect on the biofilm formation and α-toxin activity of S. aureus. The WalK protein might be a potential target of neobavaisoflavone against S. aureus.

Nondestructive rapid identification of wild Cordyceps sinensis with portable instrument.

INTRODUCTION: Cordyceps sinensis (CS) is a precious medicinal fungus. Wild CS (WCS) and artificial CS (ACS) are destroyed for their identification using traditional methods, which are time consuming and labor-intensive. Therefore, it is crucial to establish a nondestructive identification method to rapidly screen WCS. OBJECTIVE: The aim of this study was to provide technical support for rapid screening of CS and evaluation of its quality. The applicability of the model was improved through model transfer. METHODS: In this study, continuous wavelet transform was used to analyze the differences in moisture content and active components between WCS and ACS from the perspective of characteristic molecular groups. A portable instrument and a laboratory benchtop instrument were used to determine CS spectra. Partial least squares discrimination analysis was conducted for the identification of WCS and ACS while preserving the original shape of CS. Moreover, improved principal component analysis was utilized to transfer the model between the two types of near-infrared spectroscopy (NIRS) instruments. RESULTS: The results demonstrated that three peaks, at 1443, 1941, and 2183 nm, were characteristic absorption peaks. The model based on NIRS could initially provide rapid differentiation between WCS and ACS. At the same time, the accuracy of the external test set was further improved to over 95% through forward transfer. CONCLUSION: Therefore, this method could be used for rapid screening of WCS and provides technical support for the nondestructive identification of CS and initial assessment of CS quality.

Heuristic Path Search and Multi-Attribute Decision-Making-Based Routing Method for Vehicular Safety Messages.

Efficient routing in urban vehicular networks is essential for timely and reliable safety message transmission, and the selection of paths and relays greatly affects the quality of routing. However, existing routing methods usually face difficulty in finding the globally optimal transmission path due to their greedy search strategies or the lack of effective ways to accurately evaluate relay performance in intricate traffic scenarios. Therefore, we present a vehicular safety message routing method based on heuristic path search and multi-attribute decision-making (HMDR). Initially, HMDR utilizes a heuristic path search, focusing on road section connectivity, to pinpoint the most favorable routing path. Subsequently, it employs a multi-attribute decision-making (MADM) technique to evaluate candidate relay performance. The subjective and objective weights of the candidate relays are determined using ordinal relationship analysis and the Criteria Importance Through Intercriteria Correlation (CRITIC) weighting methods, respectively. Finally, the comprehensive utility values of the candidate relays are calculated in combination with the link time and the optimal relay is selected. In summary, the proposed HMDR method is capable of selecting the globally optimal transmission path, and it comprehensively considers multiple metrics and their relationships when evaluating relays, which is conducive to finding the optimal relay. The experimental results show that even if the path length is long, the proposed HMDR method gives preference to the path with better connectivity, resulting in a shorter total transmission delay for safety messages; in addition, HMDR demonstrates faster propagation speed than the other evaluated methods while ensuring better one-hop distance and one-hop delay. Therefore, it helps to improve the performance of vehicular safety message transmission in intricate traffic scenarios, thus providing timely data support for secure driving.

Should responder analyses be conducted on continuous outcomes?

Continuous outcomes are often dichotomized to classify trial subjects as responders or nonresponders, with the difference in rates of response between treatment and control defined as the "responder effect." In this article, we caution that dichotomization of continuous interval outcomes may not be best practice. Defining clinical benefit or harm for continuous interval outcomes as the difference between the means of treatment and control, that is, the "continuous treatment effect," we examine the case where treatment and control outcomes are normally distributed and differ only in location. For this case, continuous treatment effects may be considered clinically relevant if they exceed a prespecified minimum clinically important difference. In contrast, using minimum clinically important differences as dichotomization thresholds will not ensure clinically relevant responder effects. For example, in some situations, increasing the threshold may actually relax the criterion for effectiveness by increasing the calculated responder effect. Using responder effects to quantitatively assess benefit or risk of investigational drugs for continuous interval outcomes presents interpretational challenges. In particular, when the dichotomization threshold is halfway between the treatment and control outcome means, the responder effect is at a maximum with a magnitude monotonically related to the number of standard deviations between the mean outcomes of treatment and control. Large responder effect benefits may therefore reflect clinically unimportant continuous treatment effects amplified by small standard deviations, and small responder effect risks may reflect either clinically important continuous treatment effects minimized by large standard deviations, or selection of a dichotomization threshold not providing maximum responder effect.

Integrated IBD Analysis, GWAS Analysis and Transcriptome Analysis to Identify the Candidate Genes for White Spot Disease in Maize.

Foundation parents (FPs) play an irreplaceable role in maize breeding practices. Maize white spot (MWS) is an important disease in Southwest China that always seriously reduces production. However, knowledge about the genetic mechanism of MWS resistance is limited. In this paper, a panel of 143 elite lines were collected and genotyped by using the MaizeSNP50 chip with approximately 60,000 single nucleotide polymorphisms (SNPs) and evaluated for resistance to MWS among 3 environments, and a genome-wide association study (GWAS) and transcriptome analysis were integrated to reveal the function of the identity-by-descent (IBD) segments for MWS. The results showed that (1) 225 IBD segments were identified only in the FP QB512, 192 were found only in the FP QR273 and 197 were found only in the FP HCL645. (2) The GWAS results showed that 15 common quantitative trait nucleotides (QTNs) were associated with MWS. Interestingly, SYN10137 and PZA00131.14 were in the IBD segments of QB512, and the SYN10137-PZA00131.14 region existed in more than 58% of QR273's descendants. (3) By integrating the GWAS and transcriptome analysis, Zm00001d031875 was found to located in the region of SYN10137-PZA00131.14. These results provide some new insights for the detection of MWS's genetic variation mechanisms.

Characteristics, secondary transformation and odor activity evaluation of VOCs emitted from municipal solid waste incineration power plant.

Volatile organic compounds (VOCs) emitted from municipal solid waste incineration power plant (MSWIPP) plays a significant role in the formation of O3 and PM2.5 and odor pollution. Field test was performed on four MSWIPPs in an area of the North China Plain. Nonmethane hydrocarbons (NMHCs) and 102 VOCs were identified and quantified. Ozone formation potential (OFP), secondary organic aerosol formation potential (SOAFP), and odor activity of the detected VOCs were evaluated. Results showed that the average concentration of NMHCs and VOCs were 1648.6 ± 1290.4 µg/m3 and 635.3 ± 588.8 µg/m3, respectively. Aromatics (62.1%), O-VOCs (16.0%), and halo hydrocarbons (10.0%) were the main VOCs groups in the MSWIPP exhaust gas. VOCs emission factor of MSWIPP was 2.43 × 103 ± 2.27 × 103 ng/g-waste. The OFP and SOAFP of MSWIPP were 960.18 ± 2158.17 µg/m3 and 1.57 ± 3.38 µg/m3, respectively. Acrolein as the dominant VOC species was the major odor contributor with a percentage of odor contribution of 65.9%. Benzene and 1,2,4-trimethylbenzene as the dominant VOC species were the main contributors of O3 formation potentials, in which 1,2,4-trimethylbenzene was also the main contributors of SOA formation potential.

Structural Analysis and Classification of Low-Molecular-Weight Hyaluronic Acid by Near-Infrared Spectroscopy: A Comparison between Traditional Machine Learning and Deep Learning.

Confusing low-molecular-weight hyaluronic acid (LMWHA) from acid degradation and enzymatic hydrolysis (named LMWHA-A and LMWHA-E, respectively) will lead to health hazards and commercial risks. The purpose of this work is to analyze the structural differences between LMWHA-A and LMWHA-E, and then achieve a fast and accurate classification based on near-infrared (NIR) spectroscopy and machine learning. First, we combined nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) spectroscopy, two-dimensional correlated NIR spectroscopy (2DCOS), and aquaphotomics to analyze the structural differences between LMWHA-A and LMWHA-E. Second, we compared the dimensionality reduction methods including principal component analysis (PCA), kernel PCA (KPCA), and t-distributed stochastic neighbor embedding (t-SNE). Finally, the differences in classification effect of traditional machine learning methods including partial least squares-discriminant analysis (PLS-DA), support vector classification (SVC), and random forest (RF) as well as deep learning methods including one-dimensional convolutional neural network (1D-CNN) and long short-term memory (LSTM) were compared. The results showed that genetic algorithm (GA)-SVC and RF were the best performers in traditional machine learning, but their highest accuracy in the test dataset was 90%, while the accuracy of 1D-CNN and LSTM models in the training dataset and test dataset classification was 100%. The results of this study show that compared with traditional machine learning, the deep learning models were better for the classification of LMWHA-A and LMWHA-E. Our research provides a new methodological reference for the rapid and accurate classification of biological macromolecules.

Chemical Composition, Antioxidant Activity and Cytocompatibility of Polyphenolic Compounds Extracted from Food Industry Apple Waste: Potential in Biomedical Application.

Apple pomace (AP) from the food industry is a mixture of different fractions containing bioactive polyphenolic compounds. This study provides a systematic approach toward the recovery and evaluation of the physiochemical and biological properties of polyphenolic compounds from AP. We studied subcritical water extraction (SCW) and solvent extraction with ethanol from four different AP fractions of pulp, peel, seed, core, and stem (A), peel (B), seed and core (C), and pulp and peel (D). The subcritical water method at the optimum condition resulted in total polyphenolic compounds (TPC) of 39.08 ± 1.10 mg GAE per g of AP on a dry basis compared to the ethanol extraction with TPC content of 10.78 ± 0.94 mg GAE/g db. Phloridzin, chlorogenic acid, and quercetin were the main identified polyphenolics in the AP fractions using HPLC. DPPH radical scavenging activity of fraction B and subcritical water (SW) extracts showed comparable activity to ascorbic acid while all ethanolic extracts were cytocompatible toward human fibroblast (3T3-L1) and salivary gland acinar cells (NS-SV-AC). Our results indicated that AP is a rich source of polyphenolics with the potential for biomedical applications.

Improved Principal Component Analysis (IPCA): A Novel Method for Quantitative Calibration Transfer between Different Near-Infrared Spectrometers.

Given the labor-consuming nature of model establishment, model transfer has become a considerable topic in the study of near-infrared (NIR) spectroscopy. Recently, many new algorithms have been proposed for the model transfer of spectra collected by the same types of instruments under different situations. However, in a practical scenario, we need to deal with model transfer between different types of instruments. To expand model applicability, we must develop a method that could transfer spectra acquired from different types of NIR spectrometers with different wavenumbers or absorbance. Therefore, in our study, we propose a new methodology based on improved principal component analysis (IPCA) for calibration transfer between different types of spectrometers. We adopted three datasets for method evaluation, including public pharmaceutical tablets (dataset 1), corn data (dataset 2), and the spectra of eight batches of samples acquired from the plasma ethanol precipitation process collected by FT-NIR and MicroNIR spectrometers (dataset 3). In the calibration transfer for public datasets, IPCA displayed comparable results with the classical calibration transfer method using piecewise direct standardization (PDS), indicating its obvious ability to transfer spectra collected from the same types of instruments. However, in the calibration transfer for dataset 3, our proposed IPCA method achieved a successful bi-transfer between the spectra acquired from the benchtop and micro-instruments with/without wavelength region selection. Furthermore, our proposed method enabled improvements in prediction ability rather than the degradation of the models built with original micro spectra. Therefore, our proposed method has no limitations on the spectrum for model transfer between different types of NIR instruments, thus allowing a wide application range, which could provide a supporting technology for the practical application of NIR spectroscopy.