Exploring the roles of noncoding RNAs in craniofacial abnormalities: A systematic review.

Congenital craniofacial abnormalities are congenital anomalies of variable expressivity and severity with a recognizable set of abnormalities, which are derived from five identifiable primordial structures. They can occur unilaterally or bilaterally and include various malformations such as cleft lip with/without palate, craniosynostosis, and craniofacial microsomia. To date, the molecular etiology of craniofacial abnormalities is largely unknown. Noncoding RNAs (ncRNAs), including microRNAs, long ncRNAs, circular RNAs and PIWI-interacting RNAs, function as major regulators of cellular epigenetic hallmarks via regulation of various molecular and cellular processes. Recently, aberrant expression of ncRNAs has been implicated in many diseases, including craniofacial abnormalities. Consequently, this review focuses on the role and mechanism of ncRNAs in regulating craniofacial development in the hope of providing clues to identify potential therapeutic targets.

Hybrid-FHR: a multi-modal AI approach for automated fetal acidosis diagnosis.

BACKGROUND: In clinical medicine, fetal heart rate (FHR) monitoring using cardiotocography (CTG) is one of the most commonly used methods for assessing fetal acidosis. However, as the visual interpretation of CTG depends on the subjective judgment of the clinician, this has led to high inter-observer and intra-observer variability, making it necessary to introduce automated diagnostic techniques. METHODS: In this study, we propose a computer-aided diagnostic algorithm (Hybrid-FHR) for fetal acidosis to assist physicians in making objective decisions and taking timely interventions. Hybrid-FHR uses multi-modal features, including one-dimensional FHR signals and three types of expert features designed based on prior knowledge (morphological time domain, frequency domain, and nonlinear). To extract the spatiotemporal feature representation of one-dimensional FHR signals, we designed a multi-scale squeeze and excitation temporal convolutional network (SE-TCN) backbone model based on dilated causal convolution, which can effectively capture the long-term dependence of FHR signals by expanding the receptive field of each layer's convolution kernel while maintaining a relatively small parameter size. In addition, we proposed a cross-modal feature fusion (CMFF) method that uses multi-head attention mechanisms to explore the relationships between different modalities, obtaining more informative feature representations and improving diagnostic accuracy. RESULTS: Our ablation experiments show that the Hybrid-FHR outperforms traditional previous methods, with average accuracy, specificity, sensitivity, precision, and F1 score of 96.8, 97.5, 96, 97.5, and 96.7%, respectively. CONCLUSIONS: Our algorithm enables automated CTG analysis, assisting healthcare professionals in the early identification of fetal acidosis and the prompt implementation of interventions.

Mixed-Mode Adsorption of l-Tryptophan on D301 Resin through Hydrophobic Interaction/Ion Exchange/Ion Exclusion: Equilibrium and Kinetics Study.

The adsorption of l-tryptophan (l-Trp) was studied based on the hydrophobic interaction/ion exchange/ion exclusion mixed-mode adsorption resin D301. Firstly, the interaction mode between l-Trp and resin was analyzed by studying the influence of pH variation on the adsorption capability and the dissociation state of l-Trp. Secondly, the adsorption mechanism was illuminated by studying the adsorption equilibrium and kinetic behaviors. The adsorption equilibrium and a kinetics model were constructed. The augmentation of pH gradually elicited an enhancement in the adsorption capacity of l-Trp. l-Trp existing in varied dissociation states could be adsorbed by the resin, and the interaction mode relied upon the pH of the solution. An integrated adsorption equilibrium model with the coadsorption of different dissociation states of l-Trp was developed and could predict the adsorption isotherms at various pH levels satisfactorily. Both external mass transfer and intra-particle diffusion collectively imposed constraints on the mass transfer process of l-Trp onto the resin. An improved liquid film linear driving force model (ILM) was constructed, and the model provided a satisfactory fit for the adsorption kinetics curves of l-Trp at various pH levels. l-Trp molecules had a high mass transfer rate at a relatively low solution pH.

Out of the Qinghai-Tibet plateau: Genomic biogeography of the alpine monospecific genus Megadenia (Biscutelleae, Brassicaceae).

Numerous high-elevation alpine plants of the Qinghai-Tibet Plateau (QTP) also have disjunct distribution in adjacent low-altitude mountains. The out-of-QTP versus into-the-QTP hypothesis of alpine plants provide strong evidence for the highly disputed assumption of the massive ice sheet developed in the central plateau during the Last Glacial Maximum (LGM). In this study, we sequenced the genomes of most known populations of Megadenia, a monospecific alpine genus of Brassicaceae distributed primarily in the QTP, though rarely found in adjacent low-elevation mountains of north China and Russia (NC-R). All sequenced samples clustered into four geographic genetic groups: one pair was in the QTP and another was in NC-R. The latter pair is nested within the former, and these findings support the out-of-QTP hypothesis. Dating the four genetic groups and niche distribution suggested that Megadenia migrated out of the QTP to adjacent regions during the LGM. The NC-R group showed a decrease in the effective population sizes. In addition, the genes with high genetic divergences in the QTP group were mainly involved in habitat adaptations during low-altitude colonization. These findings reject the hypothesis of development massive ice sheets, and support glacial survival of alpine plants within, as well as further migration out of, the QTP.

Ultrasonic-Assisted Extraction of Antioxidants from Perilla frutescens Leaves Based on Tailor-Made Deep Eutectic Solvents: Optimization and Antioxidant Activity.

The development of natural antioxidants to replace synthetic compounds is attractive. Perilla frutescens leaves were proven to be rich in antioxidants. The extraction of antioxidants from Perilla leaves via ultrasonic-assisted extraction (UAE) based on choline chloride-based deep eutectic solvents (DESs) was studied. Firstly, several DESs were prepared, and their extraction effects were compared. Secondly, the extraction process was optimized by single-factor experiments and response surface methodology (RSM). Finally, the optimization results were verified and compared with the results of traditional solvent-based UAE. The effects of solvents on the surface cell morphology of Perilla frutescens leaves were characterized by scanning electron microscopy (SEM). Choline chloride-acetic acid-based DES (ChCl-AcA) extract showed a relatively high ferric-reducing antioxidant activity (FRAP) and 2,2-diphenyl-1-picrylhyldrazyl radical scavenging rate (DPPH). Under the optimal operating conditions (temperature 41 °C, liquid-solid ratio 33:1, ultrasonic time 30 min, water content 25%, ultrasonic power 219 W), the experimental results are as follows: DPPH64.40% and FRAP0.40 mM Fe(II)SE/g DW. The experimental and predicted results were highly consistent with a low error (<3.38%). The values of the DPPH and FRAP were significantly higher than that for the water, ethanol, and butanol-based UAE. SEM analysis confirmed that ChCl-AcA enhanced the destruction of the cell wall, so that more antioxidants were released. This study provides an eco-friendly technology for the efficient extraction of antioxidants from Perilla frutescens leaves. The cytotoxicity and biodegradability of the extract will be further verified in a future work.

ACE2 and TMPRSS2 in human saliva can adsorb to the oral mucosal epithelium.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is primarily transmitted through droplets. All human tissues with the angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serines 2 (TRMPRSS2) are potential targets of SARS-CoV-2. The role of saliva in SARS-CoV-2 transmission remains obscure. In this study, we attempted to reveal ACE2 and TRMPRSS2 protein expression in human parotid, submandibular, and sublingual glands (three major salivary glands). Then, the binding function of spike protein to ACE2 in three major salivary glands was detected. The expression of ACE2 and TMPRSS2 in human saliva from parotid glands were both examined. Exogenous recombined ACE2 and TMPRSS2 anchoring and fusing to oral mucosal epithelial cells in vitro were also unraveled. ACE2 and TMPRSS2 were found mainly to be expressed in the cytomembrane and cytoplasm of epithelial cells in the serous acinus cells in parotid and submandibular glands. Our research also discovered that the spike protein of SARS-CoV-2 binds to ACE2 in salivary glands in vitro. Furthermore, exogenous ACE2 and TMPRSS2 can anchor and fuse to oral mucosa in vitro. Thus, the expression of ACE2 and TMPRSS2 in human saliva might have implications for SARS-CoV-2 infection.

Endoplasmic reticulum stress promotes the release of exosomal PD-L1 from head and neck cancer cells and facilitates M2 macrophage polarization.

BACKGROUND: Endoplasmic reticulum (ER) stress has been found to foster the escape of cancer cells from immune surveillance and upregulate PD-L1 expression. However, the underlying mechanisms are unknown. METHODS: While analyzing the protein levels using immunofluorescence and Western blotting, the RNA levels were measured using qRT-PCR. Ten injection of exosomes into six-week-old nude mice was made through the tail vein once every other day in total. RESULTS: The expression of certain ER stress markers such as PERK (PKR-like endoplasmic reticulum kinase), ATF6 (activating transcription factor 6), and GRP78 (glucose-regulated protein 78), was found to be upregulated in the oral squamous cell carcinoma (OSCC) tissues and related to poor overall survival. There is a positive relationship between the extent of ER stress-related proteins and a cluster of PD-L1 expression and macrophage infiltration among the OSCC tissues. Further, incubation with exosomes derived from ER-stressed HN4 cells (Exo-ER) was found to upregulate PD-L1 extents in macrophages in vitro and in vivo, and macrophage polarization toward the M2 subtype was promoted by upregulating PD-L1. CONCLUSIONS: ER stress causes OSCC cells to secrete exosomal PD-L1 and upregulates PD-L1 expression in macrophages to drive M2 macrophage polarization. The delineation of a new exosome-modulated mechanism was made for OSCC-macrophage crosstalk driving tumor development and to be examined for its therapeutic use. Exosomal PD-L1 secreted by ER-stressed OSCC cells promoted M2 macrophage polarization. Video Abstract.

Preparation and Evaluation of Antioxidant Activities of Bioactive Peptides Obtained from Cornus officinalis.

The present study is a preparation of bioactive peptides from Cornus officinalis proteins by the compound enzymatic hydrolysis method. Response surface methodology (RSM) coupled with Box-Behnken design (BBD) is used to optimize the preparation process of Cornus officinalis peptides. The effects of independent variables, such as the amount of enzyme, pH value, time, extraction times and the ratio of material to liquid on the yield of peptides, are also investigated. The analysis results of the RSM model show that the optimum conditions for the extraction of Cornus officinalis peptides were a pH value of 6.76, temperature of 48.84 °C and the amount of enzyme of 0.19%. Under optimal conditions, the yield of peptides was 36.18 ± 0.26 %, which was close to the predicted yield by the RSM model. Additionally, the prepared Cornus officinalis peptides showed significant antioxidant activity; the scavenging rates of the peptides for DPPH and ·OH were 48.47% and 29.41%, respectively. The results of the cell proliferation assay revealed that the prepared Cornus officinalis peptides could promote embryo fibroblast cells proliferation and repair oxidative damage cells. These results have a practical application value in the design of novel functional food formulations by using Cornus officinalis.

FAM83A promotes proliferation and metastasis via Wnt/ß-catenin signaling in head neck squamous cell carcinoma.

This research aimed to investigate the expression and function of FAM83A in the proliferation and metastasis in head and neck squamous cell carcinoma (HNSCC). FAM83A mRNA and protein expressions in HNSCC were detected in primary HNSCC samples and cell lines. The associations between FAM83A expression and clinicopathologic variables were evaluated through tissue microarrays. Besides, FAM83A knockdown and overexpression cell lines were constructed to assess cell growth and metastasis in vitro and the relationship between FAM83A and epithelial-mesenchymal transition (EMT). Furthermore, two models of xenograft tumors in nude mice were used to assess the tumorigenicity and metastasis ability of FAM83A in vivo. In the present study, overexpression of FAM83A in HNSCC samples was significantly associated with tumor size, lymph node status and clinical tumor stages. Mechanically, FAM83A could promote HNSCC cell growth and metastasis by inducing EMT via activating Wnt/ß-catenin signaling pathway. Rescue experiment demonstrated the inhibition of ß-catenin could counteract the function of FAM83A. Also, the FAM83A knockdown could suppress tumor growth and distant metastasis in the xenograft animal models of HNSCC. In conclusion, this study identifies FAM83A as an oncogene of HNSCC. This study provides new insights into the molecular pathways that contribute to EMT in HNSCC. We revealed a previously unknown FAM83A-Wnt-ß-catenin signaling axis involved in the EMT of HNSCC. There may be a potential bi-directional signaling loop between FAM83A and Wnt/ß-catenin signaling pathway in HNSCC.

A novel procedure for purification of uridine 5'-monophosphate based on adsorption methodology using a hyper-cross-linked resin.

The conventional ion exchange process used for recovery of uridine 5'-monophosphate (UMP) from the enzymatic hydrolysate of RNA is environmentally harmful and cost intensive. In this work, an innovative benign process, which comprises adsorption technology and use of a hyper-cross-linked resin as a stationary phase is proposed. The adsorption properties of this kind of resin in terms of adsorption equilibrium as well as kinetics were evaluated. The influences of the operating conditions, i.e., initial UMP concentration, feed flow rate, and bed height on the breakthrough curves of UMP in the fixed bed system were investigated. Subsequently, a chromatographic column model was established and validated for the prediction of the experimentally attained breakthrough curves of UMP and the main impurity component (phosphate ion) with a real enzymatic hydrolysate of RNA as a feed mixture. At the end of this paper, the crystallization of UMP was carried out. The purity of the final product (uridine 5'-monophosphate disodium, UMPNa2) of over 99.5 % was obtained.

Urolithin A exerts a protective effect on lipopolysaccharide-induced acute lung injury by regulating HMGB1-mediated MAPK and NF-κB signaling pathways.

Acute lung injury (ALI) is a severe inflammatory disorder that has a high morbidity and mortality rate. Urolithin A (UA) is reported to have anti-inflammatory and anti-oxidative effects in ALI. However, its molecular mechanisms in ALI remain to be explored. Mice and BEAS-2B cells were administrated with lipopolysaccharide (LPS) to mimic the ALI model in vivo and in vitro. Hematoxylin-eosin (HE) staining was used to detect the pathological injury of lung tissues. The levels of proinflammatory cytokines in bronchoalveolar lavage fluid (BALF) and culture supernatant and the levels of oxidative stress markers in lung tissues were measured using ELISA. DCFH-DA probe was used to assess the reactive oxygen species (ROS) level. TUNEL staining and flow cytometry were performed to determine cell apoptosis. The key targets and pathways were confirmed by immunohistochemistry (IHC) and western blot. UA suppressed the pathologic damage, wet/dry weight ratio, and total protein and inflammatory cells in BALF. UA decreased neutrophil infiltration and proinflammatory cytokines production. UA reduced the level of malondialdehyde (MDA) and increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in pulmonary tissues. UA also inhibited cell apoptosis in lung tissues by decreasing Bax expression and increasing Bcl-2 expression. In addition, UA suppressed LPS-induced inflammatory factor production, ROS level, and cell apoptosis in BEAS-2B. Importantly, UA decreased the expression of HMGB1 in LPS-treated mice and BEAS-2B cells. HMGB1 overexpression greatly abrogated the inhibition of UA on inflammation, ROS, and cell apoptosis in LPS-administrated BEAS-2B. Furthermore, UA treatment suppressed the phosphorylated levels of p38, JNK, ERK, and p65 in LPS-administrated mice and BEAS-2B cells. UA alleviated lung inflammation, oxidative stress, and apoptosis in ALI by targeting HMGB1 to inactivate the MAPK/NF-κB signaling, suggesting the potential of UA to treat ALI.

Contrastive representation learning on dynamic networks.

Representation learning for dynamic networks is designed to learn the low-dimensional embeddings of nodes that can well preserve the snapshot structure, properties and temporal evolution of dynamic networks. However, current dynamic network representation learning methods tend to focus on estimating or generating observed snapshot structures, paying excessive attention to network details, and disregarding distinctions between snapshots with larger time intervals, resulting in less robustness for sparse or noisy networks. To alleviate these challenges, this paper proposes a contrastive mechanism for temporal representation learning on dynamic networks, inspired by the success of contrastive learning in visual and static network representation learning. This paper proposes a novel Dynamic Network Contrastive representation Learning (DNCL) model. Specifically, contrast objective functions are constructed using intra-snapshot and inter-snapshot contrasts to capture the network topology, node feature information, and network evolution information, respectively. Rather than estimating or generating ground-truth network features, the proposed approach maximizes mutual information between nodes from different time steps and views generated. The experimental results of link prediction, node classification, and clustering on several real-world and synthetic networks demonstrate the superiority of DNCL over state-of-the-art methods, indicating the effectiveness of the proposed approach for dynamic network representation learning.

Uncovering the phonon spectra and lattice dynamics of plastically deformable InSe van der Waals crystals.

Stacking two-dimensional (2D) van der Waals (vdW) materials in a layered bulk structure provides an appealing platform for the emergence of exotic physical properties. As a vdW crystal with exceptional plasticity, InSe offers the opportunity to explore various effects arising from the coupling of its peculiar mechanical behaviors and other physical properties. Here, we employ neutron scattering techniques to investigate the correlations of plastic interlayer slip, lattice anharmonicity, and thermal transport in InSe crystals. Not only are the interlayer slip direction and magnitude well captured by shifts in the Bragg reflections, but we also observe a deviation from the expected Debye behaviour in the heat capacity and lattice thermal conductivity. Combining the experimental data with first-principles calculations, we tentatively attribute the observed evidence of strong phonon-phonon interactions to a combination of a large acoustic-optical frequency resonance and a nesting effect. These findings correlate the macroscopic plastic slip and the microscopic lattice dynamics, providing insights into the mechano-thermo coupling and modulation in 2D vdW materials.

Identifying fetal status with fetal heart rate: Deep learning approach based on long convolution.

CTG (Cardiotocography) is an effective tool for fetal status assessment. Clinically, doctors mainly evaluate the health of fetus by observing FHR (fetal heart rate). The rapid development of Artificial Intelligence has led realization of computer-aided CTG technology, Intelligent CTG classification based on FHR is a fundamental component of these technologies. Its implementation can provide doctors with auxiliary decisions. Most of existing FHR classification methods are based on combing different deep learning models, such as CNN (Convolutional Neural Network), LSTM (Long short-term memory) and Transformer. However, these studies ignore the balance of positive and negative samples in dataset and the matching degree between model and FHR classification task, which reduces the classification accuracy. In this paper, we mainly discuss two major problems in previous FHR classification studies: reduce class imbalance and select appropriate convolution kernel. To address above two problems, we propose a data augmentation method based on ECMN (Edge Clipping and Multiscale Noise) to resolve class imbalance. Subsequently, we introduce a one-dimensional long convolutional layer, which use trend area to calculate the appropriate convolution kernel. Based on appropriate convolution kernel, an improved residual structure with attention mechanism named TGLCN (Trend-Guided Long Convolution Network) is proposed to improve FHR classification accuracy. Finally, horizontal and longitudinal experiments show that the TGLCN obtains high classification accuracy and speed of parameter adjustment.

Baicalin Exerts a Protective Effect in Diabetic Nephropathy by Repressing Inflammation and Oxidative Stress Through the SphK1/S1P/NF-κB Signaling Pathway.

Background: Inflammation and oxidative stress contribute to the development of diabetic nephropathy (DN). Baicalin (BA) shows renal protection against DN through its anti-inflammatory and anti-oxidant properties. However, the molecular mechanism by which BA exerts the therapeutic effects on DN remains to be investigated. Methods: The db/db mice and high glucose (HG)-induced HK-2 cells were used as the in vivo and in vitro model of DN, respectively. The effects of BA were assessed by detecting the related blood and urine biochemical parameters, kidney histopathology, inflammatory cytokine production, oxidative stress indicators, and apoptosis. Cell viability and apoptosis were detected by CCK-8 assay and TUNEL assay, respectively. Related protein levels were measured by an immunoblotting method. Results: In db/db model mice, BA reduced serum glucose concentration, decreased blood lipid levels, ameliorated kidney functions, and decreased histopathological changes in kidney tissues. BA also alleviated oxidative stress and inflammation in db/db mice. In addition, BA blocked the activation of sphingosine kinases type 1/sphingosine 1-phosphate (SphK1/S1P)/NF-κB pathway in db/db mice. In HK-2 cells, BA hindered HG-induced apoptosis, oxidative stress and inflammation, while overexpression of SphK1 or S1P could reverse these effects. BA alleviated HG-induced apoptosis, oxidative stress and inflammation in HK-2 cells through the S1P/NF-κB pathway. Furthermore, BA blocked the NF-κB signaling by diminishing p65 nuclear translocation via the SphK1/S1P pathway. Conclusion: Our study strongly suggests that BA protects against DN via ameliorating inflammation, oxidative stress and apoptosis through the SphK1/S1P/NF-κB pathway. This study provides a novel insight into the therapeutic effects of BA in DN.

Integrating Network Pharmacology and Experimental Validation to Elucidate the Mechanism of Yiqi Yangyin Decoction in Suppressing Non-Small-Cell Lung Cancer.

Yiqi Yangyin Decoction (YYD) is a classic traditional Chinese medicine (TCM) formulation to treat lung cancer in clinic. Nevertheless, the active ingredients, key targets, and molecular mechanisms for YYD are still poorly understood. This study is focused on elucidating the pharmacological mechanism of YYD in non-small-cell lung cancer (NSCLC) by using a combined network pharmacology approach and biological experiment validation. Online bioinformatics tools showed that 40 bioactive compounds and 229 putative targets of YYD were associated with anti-NSCLC activity. Protein-Protein Interaction (PPI) network demonstrated AKT1, SRC, JUN, TP53, and EGFR as the top five key targets for YYD against NSCLC. Through enrichment analysis, YYD was found to affect cell proliferation and apoptosis in NSCLC possibly by PI3K-AKT signaling. Molecular docking confirmed a strong binding between the main compounds (quercetin or luteolin) and EGFR. As demonstrated by CCK-8, EdU, and colony formation assays, we found a significant inhibition of YYD on cell proliferation. Moreover, YYD treatment induced cell cycle arrest by affecting p53, p21, and cyclin D1 expression. YYD administration enhanced apoptosis by changing the expression of cleaved caspase-3, Bax, and Bcl-2. Mechanistically, YYD resulted in a significant inactivation of EGFR-PI3K-AKT signaling. Furthermore, EGFR activator significantly reversed YYD-mediated proliferation inhibition and apoptosis. YYD also showed an inhibitory effect on tumor growth in mice. Together, YYD might target the EGFR-PI3K-AKT pathway to repress NSCLC progression.

Role Discovery-Guided Network Embedding Based on Autoencoder and Attention Mechanism.

Recently, network embedding (NE) is an amazing research point in complex networks and devoted to a variety of tasks. Nearly, all the methods and models of NE are based on the local, high-order, or global similarity of the networks, and few studies have focused on the role discovery or structural similarity, which is of great significance in spreading dynamics and network theory. Meanwhile, existing NE models for role discovery suffer from two limitations, that is: 1) they fail to model the varying dependencies between each node and its neighbor nodes and 2) they cannot capture the effective node features which are helpful to role discovery, which makes these methods ineffective when applied to the role discovery task. To solve the above problems of NE for role discovery or structural similarity, we propose a unified deep learning framework, called RDAA, which can effectively represent features of nodes and benefit the Role Discovery-guided NE with a deep autoencoder, while modeling the local links with an Attention mechanism. In addition, we design an elaborately binding technique to combine both parts and optimize the framework in a unified way. We conduct different experiments, including visualization, role classification, role discovery, and running time compared to popular NE methods for both proximity and structural similarity. The RDAA has better performance on all the datasets and achieves good tradeoffs.

A lightweight fetal distress-assisted diagnosis model based on a cross-channel interactive attention mechanism.

Fetal distress is a symptom of fetal intrauterine hypoxia, which is seriously harmful to both the fetus and the pregnant woman. The current primary clinical tool for the assessment of fetal distress is Cardiotocography (CTG). Due to subjective variability, physicians often interpret CTG results inconsistently, hence the need to develop an auxiliary diagnostic system for fetal distress. Although the deep learning-based fetal distress-assisted diagnosis model has a high classification accuracy, the model not only has a large number of parameters but also requires a large number of computational resources, which is difficult to deploy to practical end-use scenarios. Therefore, this paper proposes a lightweight fetal distress-assisted diagnosis network, LW-FHRNet, based on a cross-channel interactive attention mechanism. The wavelet packet decomposition technique is used to convert the one-dimensional fetal heart rate (FHR) signal into a two-dimensional wavelet packet coefficient matrix map as the network input layer to fully obtain the feature information of the FHR signal. With ShuffleNet-v2 as the core, a local cross-channel interactive attention mechanism is introduced to enhance the model's ability to extract features and achieve effective fusion of multichannel features without dimensionality reduction. In this paper, the publicly available database CTU-UHB is used for the network performance evaluation. LW-FHRNet achieves 95.24% accuracy, which meets or exceeds the classification results of deep learning-based models. Additionally, the number of model parameters is reduced many times compared with the deep learning model, and the size of the model parameters is only 0.33 M. The results show that the lightweight model proposed in this paper can effectively aid in fetal distress diagnosis.

Metal-Organic Framework for Hypoxia/ROS/pH Triple-Responsive Cargo Release.

Nanoparticulate antitumor photodynamic therapy (PDT) is suffering from a very short lifetime, limited diffusion distance of reactive oxygen species (ROS). Herein, a hypoxia/ROS/pH triple-responsive metal-organic framework (MOF) is designed to facilitate the on-demand release of photosensitizers and hence enhanced PDT efficacy. Tailored azo-containing imidazole ligand is coordinated with zinc to form MOF where photosensitizer (Chlorin e6/Ce6) is encapsulated. Azo can be reduced by overexpressed azoreductase in hypoxic tumor cells, resulting in depletion of glutathione (GSH) and thioredoxin (Trx) which are major antioxidants against ROS oxidative damage in PDT, resulting in rapid cargo release and additional efficacy amplification. The imidazole ionization causes a proton sponge effect to ensure the disintegration of the nanocarriers in acidic organelles, allowing the rapid release of Ce6 through lysosome escape. Under light irradiation, ROS produced by Ce6 may oxidize imidazole to urea, resulting in rapid cargo release. All of the triggers are expected to show interactive synergism. The pH- and hypoxia-responsiveness can improve the release rate of Ce6 for enhanced PDT therapy, whereas the consumption of oxygen by PDT may induce elevated hypoxia and hence in turn enhanced cargo release. This work highlights the role of triple-responsive nanocarriers for triggered photosensitizer release and improved antitumor PDT efficacy.

Driving Pressure-Guided Ventilation in Obese Patients Undergoing Laparoscopic Sleeve Gastrectomy: A Randomized Controlled Trial.

Purpose: This study aims to compare the conventional lung protective ventilation strategy (LPVS) with driving pressure-guided ventilation in obese patients undergoing laparoscopic sleeve gastrectomy (LSG). Methods: Forty-five patients undergoing elective LSG under general anesthesia were randomly assigned to the conventional LPVS group (group L) or the driving pressure-guided ventilation group (group D) using random numbers generated by Excel. The primary outcome was the driving pressure of both groups 90 min after pneumoperitoneum. Results: After 30 min of pneumoperitoneum, 90 min of pneumoperitoneum, 10 min of closing the pneumoperitoneum, and restoring the supine position, the driving pressure of group L and group D were 20.0 ± 2.9 cm H2O vs 16.6 ± 3.0 cm H2O (P < 0.001), 20.7 ± 3.2 cm H2O vs 17.3 ± 2.8 cm H2O (P < 0.001), and 16.3 ± 3.1 cm H2O vs 13.3 ± 2.5 cm H2O (P = 0.001), respectively; the respiratory compliance of groups L and D were 23.4 ± 3.7 mL/cm H2O vs 27.6 ± 5.1 mL/cm H2O (P = 0.003), 22.7 ± 3.8 mL/cm H2O vs 26.4 ± 3.5 mL/cm H2O (P = 0.005), and 29.6 ± 6.8 mL/cm H2O vs 34.7 ± 5.3 mL/cm H2O (P = 0.007), respectively. The intraoperative PEEP in groups L and group D was 5 (5-5) cm H2O vs 10 (9-11) cm H2O (P < 0.001). Conclusion: An individualized peep-based driving pressure-guided ventilation strategy can reduce intraoperative driving pressure and increase respiratory compliance in obese patients undergoing LSG.