Challenges in Application: Gelation Strategies of DAT-Based Hydrogel Scaffolds.

Decellularized adipose tissue (DAT) has great clinical applicability, owing to its abundant source material, natural extracellular matrix microenvironment, and nonimmunogenic attributes, rendering it a versatile resource in the realm of tissue engineering. However, practical implementations are confronted with multifarious limitations. Among these, the selection of an appropriate gelation strategy serves as the foundation for adapting to diverse clinical contexts. The cross-linking strategies under varying physical or chemical conditions exert profound influences on the ultimate morphology and therapeutic efficacy of DAT. This review sums up the processes of DAT decellularization and subsequent gelation, with a specific emphasis on the diverse gelation strategies employed in recent experimental applications of DAT. The review expounds upon methodologies, underlying principles, and clinical implications of different gelation strategies, aiming to offer insights and inspiration for the application of DAT in tissue engineering and advance research for tissue engineering scaffold development.

A magnetic nanozyme platform for bacterial colorimetric detection and chemodynamic/photothermal synergistic antibacterial therapy.

Rapid, convenient, and sensitive detection of bacteria and development of novel antibacterial materials are conducive to accurate treatment of bacterial infection and reducing the generation of drug-resistant bacteria caused by overuse of antibiotics. A dual-function magnetic nanozyme, Fc-MBL@rGO@Fe3O4, has been constructed with broad-spectrum bacterial affinity and good peroxidase-like activity. Detection signal amplification was realized in the presence of 3,3',5,5'-tetramethylbenzidine (TMB) with a detection limit of 26 CFU/mL. In addition, the excellent photothermal properties of Fc-MBL@rGO@Fe3O4 could realize synergistic chemodynamic/photothermal antibacterial therapy. Furthermore, the good bacterial affinity of Fc-MBL@rGO@Fe3O4 enhances the accurate and rapid attack of hydroxyl radical (·OH) on the bacterial membrane and achieves efficient sterilization (100%) at low concentration (40 µg/mL) and mild temperature (47℃). Notably, Fc-MBL@rGO@Fe3O4 has a broad spectrum of antibacterial activity against Gram-negative, Gram-positive, and drug-resistant bacteria. The magnetic nanoplatform integrating detection-sterilization not only meets the need for highly sensitive and accurate detection in different scenarios, but can realize low power density NIR-II light-responsive chemodynamic/photothermal antibacterial therapy, which has broad application prospects.

A study of the biological effects of low-level light.

Low-level light therapy (LLLT), also known as photo biomodulation (PBM), is a type of optical therapy that uses red or near-infrared lasers or light-emitting diodes (LEDs) for medical treatment. The laser wavelengths involved in PBM typically range between 600-700 nm and 780-1100 nm, with power densities ranging between 5 mW/cm2 and 5 W/cm2. PBM is a series of biochemical cascades exhibited by biological tissues after absorbing a certain amount of energy from light. PBM has been widely used in clinical practice in the past 20 years, and numerous clinical trials have demonstrated its biological efficacy. However, the underlying mechanisms have not yet been fully explored. In this paper, we have summarized the research into PBM over the past two decades, to identify the important mechanisms of the biological effects of PBM from the perspective of molecular mechanisms, cellular levels, and tissue changes. We hope our study provide a theoretical basis for future investigations into the underlying mechanisms.

Programmable Aptasensor for Regulating CRISPR/Cas12a Activity.

CRISPR-mediated aptasensors have gained prevalence for detecting non-nucleic acid targets. However, there is an urgent need to develop an easily customizable design to improve the signal-to-noise ratio, enhance universality, and expand the detection range. In this article, we report a CRISPR-mediated programmable aptasensor (CPAS) platform. The platform includes single-stranded DNA comprising the aptamer sequence, locker DNA, and a crRNA recognition region, forming a hairpin structure through complementary hybridization. With T4 DNA polymerase, the crRNA recognition region was transformed into a complete double-stranded DNA through stem-loop extension, thereby activating the trans-cleavage activity of Cas 12a and generating fluorescence signals. The specific binding between the target molecule and aptamer disrupted the formation of the hairpin structure, altering the fluorescence signals. Notably, the CPAS platform allows for easy customization by simply changing the aptamer sequence and locker DNA, without entailing adjustments to the crRNA. The optimal number of bases in the locker DNA was determined to be seven nucleotides for the SARS-CoV-2 spike (S) protein and four nucleotides for ATP. The CPAS platform exhibited high sensitivity for S protein and ATP detection. Integration with a lateral flow assay enabled sensitive detection within 1 h, revealing its excellent potential for portable analysis.

Gasotransmitter Research Advances in Respiratory Diseases.

Significance: Gasotransmitters are small gas molecules that are endogenously generated and have well-defined physiological functions. The most well-defined gasotransmitters currently are nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), while other potent gasotransmitters include ammonia, methane, cyanide, hydrogen gas, and sulfur dioxide. Gasotransmitters play a role in various respiratory diseases such as asthma, chronic obstructive pulmonary disease, obstructive sleep apnea, lung infection, bronchiectasis, cystic fibrosis, primary ciliary dyskinesia, and COVID-19. Recent Advances: Gasotransmitters can act as biomarkers that facilitate disease diagnosis, indicate disease severity, predict disease exacerbation, and evaluate disease outcomes. They also have cell-protective properties, and many studies have been conducted to explore their pharmacological applications. Innovative drug donors and drug delivery methods have been invented to amplify their therapeutic effects. Critical Issues: In this article, we briefly reviewed the physiological and pathophysiological functions of some gasotransmitters in the respiratory system, the progress in detecting exhaled gasotransmitters, as well as innovative drugs derived from these molecules. Future Directions: The current challenge for gasotransmitter research includes further exploring their physiological and pathological functions, clarifying their complicated interactions, exploring suitable drug donors and delivery devices, and characterizing new members of gasotransmitters. Antioxid. Redox Signal. 40, 168-185.

Comparative analysis of the synergetic effects of Diwuyanggan prescription on high fat diet-induced non-alcoholic fatty liver disease using untargeted metabolomics.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders worldwide and had no approved pharmacological treatments. Diwuyanggan prescription (DWYG) is a traditional Chinese medicine preparation composed of 5 kinds of herbs, which has been used for treating chronic liver diseases in clinic. Whereas, the synergistic mechanism of this prescription for anti-NAFLD remains unclear. In this study, we aimed to demonstrate the synergetic effect of DWYG by using the disassembled prescriptions and untargeted metabolomics research strategies. The therapeutic effects of the whole prescription of DWYG and the individual herb were divided into six groups according to the strategy of disassembled prescriptions, including DWYG, Artemisia capillaris Thunb. (AC), Curcuma longa L. (CL), Schisandra chinensis Baill. (SC), Rehmannia glutinosa Libosch. (RG) and Glycyrrhiza uralensis Fisch. (GU) groups. The high fat diets-induced NAFLD mice model was constructed to evaluate the efficacy effects of DWYG. An untargeted metabolomics based on the UPLC-QTOF-MS/MS approach was carried out to make clear the synergetic effect on the regulation of metabolites dissecting the united mechanisms. Experimental results on animals revealed that the anti-NAFLD effect of DWYG prescription was better than the individual herb group in reducing liver lipid deposition and restoring the abnormality of lipidemia. In addition, further metabolomics analysis indicated that 23 differential metabolites associated with the progression of NAFLD were identified and 19 of them could be improved by DWYG. Compared with five single herbs, DWYG showed the most extensive regulatory effects on metabolites and their related pathways, which were related to lipid and amino acid metabolisms. Besides, each individual herb in DWYG was found to show different degrees of regulatory effects on NAFLD and metabolic pathways. SC and CL possessed the highest relationship in the regulation of NAFLD. Altogether, these results provided an insight into the synergetic mechanisms of DWYG from the metabolic perspective, and also supported a scientific basis for the rationality of clinical use of this prescription.

Insight into extracellular vesicles in vascular diseases: intercellular communication role and clinical application potential.

BACKGROUND: Cells have been increasingly known to release extracellular vesicles (EVs) to the extracellular environment under physiological and pathological conditions. A plethora of studies have revealed that EVs contain cell-derived biomolecules and are found in circulation, thereby implicating them in molecular trafficking between cells. Furthermore, EVs have an effect on physiological function and disease development and serve as disease biomarkers. MAIN BODY: Given the close association  between EV circulation and vascular disease, this review aims to provide a brief introduction to EVs, with a specific focus on the EV cargoes participating in pathological mechanisms, diagnosis, engineering, and clinical potential, to highlight the emerging evidence suggesting promising targets in vascular diseases. Despite the expansion of research in this field, some noticeable limitations remain for clinical translational research. CONCLUSION: This review makes a novel contribution to a summary of recent advances and a perspective on the future of EVs in vascular diseases. Video Abstract.

Biodegradation of Benzo[a]pyrene by a White-Rot Fungus Phlebia acerina: Surfactant-Enhanced Degradation and Possible Genes Involved.

Polycyclic aromatic hydrocarbons (PAHs) are persistent environmental pollutants that pose a threat to human health. Among these PAHs, benzo[a]pyrene (BaP), a five-ring compound, exhibits high resistance to biodegradation. White-rot fungus Phlebia acerina S-LWZ20190614-6 has demonstrated higher BaP degradation capabilities compared with Phanerochaete chrysosporium and P. sordida YK-624, achieving a degradation rate of 57.7% after 32 days of incubation under a ligninolytic condition. To further enhance the biodegradation rate, three nonionic surfactants were used, and the addition of 1 or 2 g·L-1 of polyethylene glycol monododecyl ether (Brij 30) resulted in nearly complete BaP biodegradation by P. acerina S-LWZ20190614-6. Interestingly, Brij 30 did not significantly affect the activity of manganese peroxidase and lignin peroxidase, but it did decrease laccase activity. Furthermore, the impact of cytochrome P450 on BaP degradation by P. acerina S-LWZ20190614-6 was found to be relatively mild. Transcriptomic analysis provided insights into the degradation mechanism of BaP, revealing the involvement of genes related to energy production and the synthesis of active enzymes crucial for BaP degradation. The addition of Brij 30 significantly upregulated various transferase and binding protein genes in P. acerina S-LWZ20190614-6. Hence, the bioremediation potential of BaP by the white-rot fungus P. acerina S-LWZ20190614-6 holds promise and warrants further exploration.

Diet Restriction Impact on High-Fat-Diet-Induced Obesity by Regulating Mitochondrial Cardiolipin Biosynthesis and Remodeling.

Diet restriction (DR) ameliorates obesity by regulating mitochondrial function. Cardiolipin (CL), a mitochondrial phospholipid, is closely associated with mitochondrial function. This study aimed to evaluate the anti-obesity effects of graded levels of DR based on mitochondrial CL levels in the liver. Obese mice were treated with 0%, 20%, 40%, and 60% reductions in the normal diet compared to normal animals (0 DR, 20 DR, 40 DR, and 60 DR groups, respectively). Biochemical and histopathological analyses were performed to evaluate the ameliorative effects of DR on obese mice. The altered profile of mitochondrial CL in the liver was explored using a targeted metabolomics strategy by ultra-high-pressure liquid chromatography MS/MS coupled with quadrupole time-of-flight mass spectrometry. Finally, gene expression associated with CL biosynthesis and remodeling was quantified. Tissue histopathology and biochemical index evaluations revealed significant improvements in the liver after DR, except for the 60 DR group. The variation in mitochondrial CL distribution and DR levels showed an inverted U-shape, and the CL content in the 40 DR group was the most upregulated. This result is consistent with the results of the target metabolomic analysis, which showed that 40 DR presented more variation. Furthermore, DR led to increased gene expression associated with CL biosynthesis and remodeling. This study provides new insights into the mitochondrial mechanisms underlying DR intervention in obesity.

Does paraspinal muscle morphometry predict functional status and re-operation after lumbar spinal surgery? A systematic review and meta-analysis.

OBJECTIVES: Whether paraspinal muscle degeneration is related to poor clinical outcomes after lumbar surgery is still indistinct, which limits its clinical application. This study aimed to evaluate the predictive value of paraspinal muscle morphology on functional status and re-operation after lumbar spinal surgery. METHODS: A review of the literature was conducted using a total of 6917 articles identified from a search of PubMed, EMBASE, and Web of Science databases through September 2022. A full-text review of 140 studies was conducted based on criteria including an objective assessment of preoperative paraspinal muscle morphology including multifidus (MF), erector spinae (ES), and psoas major (PS) in addition to measuring its relationship to clinical outcomes including Oswestry disability index (ODI), pain and revision surgery. Meta-analysis was performed when required metrics could be calculated in ≥ three studies, otherwise vote counting model was a good alternative to show the effect direction of evidence. The standardized mean difference (SMD) and 95% confidence interval (CI) were calculated. RESULTS: A total of 10 studies were included in this review. Of them, five studies with required metrics were included in the meta-analysis. The meta-analysis suggested that higher preoperative fat infiltration (FI) of MF could predict higher postoperative ODI scores (SMD = 0.33, 95% CI 0.16-0.50, p = 0.0001). For postoperative pain, MF FI could also be an effective predictor for persistent low back pain after surgery (SMD = 0.17, 95% CI 0.02-0.31, p = 0.03). However, in the vote count model, limited evidence was presented for the prognostic effects of ES and PS on postoperative functional status and symptoms. In terms of revision surgery, there was conflicting evidence that FI of MF and ES could predict the incidence of revision surgery in the vote count model. CONCLUSION: The assessment of MF FI could be a viable method to stratify patients with lumbar surgery by the risk of severe functional disability and low back pain. KEY POINTS: • The fat infiltration of multifidus can predict postoperative functional status and low back pain after lumbar spinal surgery. • The preoperative evaluation of paraspinal muscle morphology is conducive for surgeons.

Association between gestational weight gain and preterm birth and post-term birth: a longitudinal study from the National Vital Statistics System database.

BACKGROUND: To evaluate the association between gestational weight gain (GWG) and preterm birth and post-term birth. METHODS: This longitudinal-based research studied singleton pregnant women from the National Vital Statistics System (NVSS) (2019). Total GWG (kg) was converted to gestational age-standardized z scores. The z-scores of GWG were divided into four categories according to the quartile of GWG, and the quantile 2 interval was used as the reference for the analysis. Univariate and multivariate logistic regression analyses were performed to investigate the association between GWG and preterm birth, post-term birth, and total adverse outcome (preterm birth + post-term birth). Subgroup analysis stratified by pre-pregnancy body mass index (BMI) was used to estimate associations between z-scores and outcomes. RESULTS: Of the 3,100,122 women, preterm birth occurred in 9.45% (292,857) population, with post-term birth accounting for 4.54% (140,851). The results demonstrated that low GWG z-score [odds ratio (OR): 1.04, 95% confidence interval (CI): 1.03 to 1.05, P < 0.001], and higher GWG z-scores (quantile 3: OR: 1.42, 95% CI: 1.41 to 1.44, P < 0.001; quantile 4: OR: 2.79, 95% CI: 2.76 to 2.82, P < 0.001) were positively associated with preterm birth. Low GWG z-score (OR: 1.18, 95% CI: 1.16 to 1.19, P < 0.001) was positively associated with an increased risk of post-term birth. However, higher GWG z-scores (quantile 3: OR: 0.84, 95% CI: 0.83 to 0.85, P < 0.001; quantile 4: 0.59, 95% CI: 0.58 to 0.60, P < 0.001) was associated with a decreased risk of post-term birth. In addition, low GWG z-score and higher GWG z-scores were related to total adverse outcome. A subgroup analysis demonstrated that pre-pregnancy BMI, low GWG z-score was associated with a decreased risk of preterm birth among BMI-obesity women (OR: 0.96, 95% CI: 0.94 to 0.98, P < 0.001). CONCLUSION: Our result suggests that the management of GWG may be an important strategy to reduce the number of preterm birth and post-term birth.

Alkaline ball-milled peanut-hull biosorbent effectively removes aqueous organic dyes.

Advanced biosorbents increasingly attract attention for their application in environment remediation. Here, a facile one-step approach to alkaline ball milling was used to synthesize a porous peanut hull biosorbent without heating. The alkaline ball-milled peanut-hull (ABP) biosorbent was characterized for its ability to remove Congo red (CR), titan yellow (TY), and methyl violet (MV) from aqueous solutions. ABP processed abundant O-containing functional groups and developed porosity, resulting in maximum sorption capacities of 4864.4 (CR), 455.9 (TY), and 126.1 (MV) mg g-1. Freundlich isotherm and PSO kinetic models best fit the anionic dye's (CR and TY) adsorption by ABP, indicating multiple mechanisms might control the adsorption process. Freundlich and PFO kinetics models best described cationic MV adsorption by ABP, suggesting the adsorption of cationic dye could also be governed by multi-mechanisms but less heterogeneous than that of anionic dye. The results suggest that alkaline ball-milling is promising approach to converting biomass into advanced biosorbents for organic dyes, especially anionic ones.

Silencing of circular RNA circPDE5A suppresses neuroblastoma progression by targeting the miR-362-5p/NOL4L axis.

OBJECTIVE: Neuroblastoma (NB) is the most common extra-cranial solid tumour in early childhood. Circular RNAs (circRNAs) have been implicated in the development of NB. The purpose of the current study was to explore the molecular action of circRNA phosphodiesterase 5 A (circPDE5A) in NB malignant progression. MATERIALS AND METHODS: The expression levels of circPDE5A, miR-362-5p and nucleolar protein 4 like (NOL4L) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTS) assay. Cell migration and invasion were evaluated by transwell assay. The levels of glucose consumption and lactate production were measured using the commercial assay kits. Targeted correlations among circPDE5A, miR-362-5p and NOL4L were confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. In vivo assays were performed to examine the role of circPDE5A in tumour growth in vivo. RESULTS: Our results revealed that circPDE5A was up-regulated in NB tissues and cells. The silencing of circPDE5A suppressed NB cell proliferation, migration, invasion, and glycolysis in vitro and diminished tumour growth in vivo. Moreover, circPDE5A directly targeted miR-362-5p by binding to miR-362-5p. CircPDE5A silencing impeded NB malignant progression in vitro through up-regulating miR-362-5p. Furthermore, NOL4L was a direct target of miR-362-5p, and NOL4L mediated the regulation of miR-362-5p on NB malignant progression in vitro. Additionally, circPDE5A functioned as a regulator of NOL4L expression via targeting miR-362-5p. CONCLUSIONS: Our current findings identified that the knockdown of circPDE5A suppressed NB malignant progression at least in part by the regulation of the miR-362-5p/NOL4L axis, providing a novel rationale for developing circPDE5A as a potential target for NB management.

Methyltransferase-like 3 (METTL3) Epigenetically Modulates Glutathione Peroxidase 4 (GPX4) Expression to Affect Asthma.

Asthma, a prevalent chronic airway inflammatory condition, poses a significant health challenge. In this study, we delved into the regulatory mechanisms governing asthma, focusing on Methyltransferase-like 3 (METTL3). Through an ovalbumin (OVA)-induced mouse model and interleukin-13 (IL-13)-induced cell model, we mimicked the in vivo and in vitro functions of METTL3 in asthma. Our research revealed that METTL3 expression significantly decreased in asthma-induced mice and IL-13-stimulated cells compared to the control group. Moreover, METTL3 overexpression enhanced bronchial epithelial cell viability and proliferation. Mechanistically, we observed elevated levels of total iron, Fe2+, malondialdehyde (MDA), lipid reactive oxygen species (ROS), alongside reduced glutathione (GSH) levels in IL-13-stimulated cells. Remarkably, METTL3 overexpression counteracted these effects, suggesting a pivotal role in mitigating asthma-related oxidative stress. Furthermore, our study highlighted the involvement of N6-methyladenosine methylation (m6A) modification, where METTL3 regulated the m6A modification of glutathione peroxidase 4 (GPX4) RNA, impacting RNA stability. Knockdown of METTL3 suppressed m6A modification on GPX4 RNA, impairing its stability and contributing to IL-13-induced ferroptosis. Interestingly, METTL3 overexpression not only inhibited cell ferroptosis but also alleviated asthma symptoms. Our findings shed light on the epigenetic regulation of asthma through METTL3-mediated m6A modification, offering potential therapeutic avenues for this prevalent inflammatory disease.

Noncoding RNAs Are Promising Therapeutic Targets for Diabetic Retinopathy: An Updated Review (2017-2022).

Diabetic retinopathy (DR) is the most common complication of diabetes. It is also the main cause of blindness caused by multicellular damage involving retinal endothelial cells, ganglial cells, and pigment epithelial cells in adults worldwide. Currently available drugs for DR do not meet the clinical needs; thus, new therapeutic targets are warranted. Noncoding RNAs (ncRNAs), a new type of biomarkers, have attracted increased attention in recent years owing to their crucial role in the occurrence and development of DR. NcRNAs mainly include microRNAs, long noncoding RNAs, and circular RNAs, all of which regulate gene and protein expression, as well as multiple biological processes in DR. NcRNAs, can regulate the damage caused by various retinal cells; abnormal changes in the aqueous humor, exosomes, blood, tears, and the formation of new blood vessels. This study reviews the different sources of the three ncRNAs-microRNAs, long noncoding RNAs, and circular RNAs-involved in the pathogenesis of DR and the related drug development progress. Overall, this review improves our understanding of the role of ncRNAs in various retinal cells and offers therapeutic directions and targets for DR treatment.

Sex Differences of Cardiolipin in Tissue Distribution Based on Targeted Lipidomic Analysis by UHPLC-QTOF-MS/MS.

Cardiolipins (CLs) are involved in ATP production, mitochondria biogenesis, apoptosis and mitophagy. Their tissue distribution can provide insight into the function of mitochondria and related diseases. However, the reports on tissue distribution of CLs remain limited. In this research, CLs were identified from heart, liver, kidney, spleen, lung, skeletal muscle, and brain using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS). Then, the distribution and sex difference of CLs in seven tissues were compared by a targeted lipidomic approach. A total of 88 CLs were identified, of which 58, 51, 57, 58, 50, 61 and 52 CLs were found in heart, liver, kidney, spleen, lung, skeletal muscle, and brain, respectively. Compared with the distribution of CLs in heart, liver, kidney, and skeletal muscle, the CLs in spleen, lung, and brain showed significant differences. Moreover, the results indicated that there were sex differences of CLs in liver and kidney. A total of 16 CLs in liver tissue and 21 CLs in kidney tissue, with significant sex differences, were screened. Our findings in the targeted lipidomic analysis demonstrated that tissue distribution of CLs was essential in the dynamic states and sex differences of CLs, which might provide evidence for the mitochondrial-related mechanism under physiological and pathological conditions.

Single-cell RNA sequencing in atherosclerosis: Mechanism and precision medicine.

Atherosclerosis is the pathological basis of various vascular diseases, including those with high mortality, such as myocardial infarction and stroke. However, its pathogenesis is complex and has not been fully elucidated yet. Over the past few years, single-cell RNA sequencing (scRNA-seq) has been developed and widely used in many biological fields to reveal biological mechanisms at the cellular level and solve the problems of cellular heterogeneity that cannot be solved using bulk RNA sequencing. In this review, we briefly summarize the existing scRNA-seq technologies and focus on their application in atherosclerosis research to provide insights into the occurrence, development and treatment of atherosclerosis.

Value of Serum miR-34a and Ang-1 in Severity Evaluation and Prognosis of Neonatal Respiratory Distress Syndrome.

Methods: A total of 96 neonates with RDS admitted to the hospital from February 2020 to April 2021 were selected as the research subjects. According to the neonatal critical illness score, the subjects were divided into non-critical group (n = 50), critical group (n = 27), and extremely critical group (n = 19). According to survival status, the subjects were divided into survival group (n = 76) and death group (n = 20). Serum miR-34a and Ang-1 levels and NCIS were compared between RDS neonates with different severity and prognosis. The predictive value of serum miR-34a, Ang-1, and NCIS for death was analyzed using the receiver operating characteristic (ROC) curve. Results: Serum miR-34a and Ang-1 levels and NCIS were significantly different in the 3 groups (P < 0.05). Serum miR-34a level decreased in order, while serum Ang-1 level and NCIS increased in order from the extremely critical group, the critical group to the non-critical group (P < 0.05). The survival group had lower serum miR-34a level and higher Ang-1 level and NCIS than the death group (P < 0.05). ROC curve analysis showed that the area under the curve (AUC) values of serum miR-34a, Ang-1, and NCIS to predict death of RDS neonates were 0.745, 0.7667, and 0.736. The cutoff values were 1.175, 6.815 ng/mL, and 85 points. The AUC of joint prediction with the three was 0.924, significantly larger than that of each index. The sensitivity and specificity were 94.70% and 90.00%. Conclusion: Serum miR-34a, Ang-1, and NCIS are closely related to the severity and prognosis of neonatal RDS. Combined detection of the three is helpful for prognosis of neonatal RDS.

Diagnosing Diabetic Retinopathy in OCTA Images Based on Multilevel Information Fusion Using a Deep Learning Framework.

Objective: As an extension of optical coherence tomography (OCT), optical coherence tomographic angiography (OCTA) provides information on the blood flow status at the microlevel and is sensitive to changes in the fundus vessels. However, due to the distinct imaging mechanism of OCTA, existing models, which are primarily used for analyzing fundus images, do not work well on OCTA images. Effectively extracting and analyzing the information in OCTA images remains challenging. To this end, a deep learning framework that fuses multilevel information in OCTA images is proposed in this study. The effectiveness of the proposed model was demonstrated in the task of diabetic retinopathy (DR) classification. Method: First, a U-Net-based segmentation model was proposed to label the boundaries of large retinal vessels and the foveal avascular zone (FAZ) in OCTA images. Then, we designed an isolated concatenated block (ICB) structure to extract and fuse information from the original OCTA images and segmentation results at different fusion levels. Results: The experiments were conducted on 301 OCTA images. Of these images, 244 were labeled by ophthalmologists as normal images, and 57 were labeled as DR images. An accuracy of 93.1% and a mean intersection over union (mIOU) of 77.1% were achieved using the proposed large vessel and FAZ segmentation model. In the ablation experiment with 6-fold validation, the proposed deep learning framework that combines the proposed isolated and concatenated convolution process significantly improved the DR diagnosis accuracy. Moreover, inputting the merged images of the original OCTA images and segmentation results further improved the model performance. Finally, a DR diagnosis accuracy of 88.1% (95%CI ± 3.6%) and an area under the curve (AUC) of 0.92 were achieved using our proposed classification model, which significantly outperforms the state-of-the-art classification models. As a comparison, an accuracy of 83.7 (95%CI ± 1.5%) and AUC of 0.76 were obtained using EfficientNet. Significance. The visualization results show that the FAZ and the vascular region close to the FAZ provide more information for the model than the farther surrounding area. Furthermore, this study demonstrates that a clinically sophisticated designed deep learning model is not only able to effectively assist in the diagnosis but also help to locate new indicators for certain illnesses.

The chirality determination of amino acids by forming complexes with cyclodextrins and metal ions using ion mobility spectrometry, and a DFT calculation.

Chiral recognition is of highly interest in the areas of chemistry, pharmaceuticals, and bioscience. An effective strategy of enantiomeric determination of amino acids (AAs) was developed in this work. All 19 natural AAs enantiomers can be easily distinguished by ion mobility-mass spectrometry of the non-covalent complexes of AAs with cyclodextrins (α-CD, ß-CD and γ-CD) and Mg2+ without any chemical derivatization. Differences of the mobilities between the enantiomers' complexes is from 0.006 to 0.058 V s/cm2. In addition, the complex of [ß-CD + Phe + Mg]2+ was selected as an example to study the relative quantification by measuring L/D-Phe at different molar ratio of 10:1 to 1:10 in the µM range, resulting in a good linearity (R2 > 0.99) and high sensitivity at 2 µM. A DFT calculation was also performed to illustrate the detailed molecular structure of the complexes of CDs, Mg2+ and D- or L-Phe. Both experiment and theoretical calculation showed that Mg2+ plays an important role in host/guest interactions, which changed the molecular conformations by non-covalent interaction between Mg2+ and CDs, and resulted in the different collision cross-sections of the complex ions of CDs, Mg2+ and D- or L-AAs in the gas phase. This effective and convenient strategy could potentially be utilized in scientific research and industry for routine enantiomeric determination of natural AAs, peptides and some other small chiral biomolecules such as non-natural AAs and carboxylic acid-containing drugs.