InDEP: an interpretable machine learning approach to predict cancer driver genes from multi-omics data.

Cancer driver genes are critical in driving tumor cell growth, and precisely identifying these genes is crucial in advancing our understanding of cancer pathogenesis and developing targeted cancer drugs. Despite the current methods for discovering cancer driver genes that mainly rely on integrating multi-omics data, many existing models are overly complex, and it is difficult to interpret the results accurately. This study aims to address this issue by introducing InDEP, an interpretable machine learning framework based on cascade forests. InDEP is designed with easy-to-interpret features, cascade forests based on decision trees and a KernelSHAP module that enables fine-grained post-hoc interpretation. Integrating multi-omics data, InDEP can identify essential features of classified driver genes at both the gene and cancer-type levels. The framework accurately identifies driver genes, discovers new patterns that make genes as driver genes and refines the cancer driver gene catalog. In comparison with state-of-the-art methods, InDEP proved to be more accurate on the test set and identified reliable candidate driver genes. Mutational features were the primary drivers for InDEP's identifying driver genes, with other omics features also contributing. At the gene level, the framework concluded that substitution-type mutations were the main reason most genes were identified as driver genes. InDEP's ability to identify reliable candidate driver genes opens up new avenues for precision oncology and discovering new biomedical knowledge. This framework can help advance cancer research by providing an interpretable method for identifying cancer driver genes and their contribution to cancer pathogenesis, facilitating the development of targeted cancer drugs.

Valproic acid increased the efficacy of EGFR TKIs on EGFR/TP53 co-mutated lung cancers and downregulated mutant-p53 levels.

The TP53 tumor suppressor is the most frequently mutated gene in human cancers. For p53-targeted therapy, one of the strategies was targeting mutant p53 for degradation. In EGFR-mutated lung cancer patients, concurrent TP53 mutation was associated with faster resistance to EGFR-TKIs. In this study, we discovered that valproic acid (VPA), a widely prescribed antiseizure medication, had a synergic effect on sensitive as well as acquired resistant lung cancers with EGFR/TP53 co-mutation in combination with EGFR-TKIs. In both in vitro and in vivo models, VPA greatly improved the efficacy of EGFR-TKIs, including forestalling the occurrence of acquired resistance and increasing the sensitivity to EGFR-TKIs. Mechanistically, VPA dramatically promoted degradation of mutant p53 in both sensitive and acquired resistant cells while inhibited mutant TP53 mRNA transcription only in sensitive cells. Together, this study suggested that VPA combination treatment could have beneficial effects on EGFR-mutant lung cancers with concurrent p53 mutation in both early and late stages, expanding the potential clinical applications for VPA.

Nrf2/FSP1/CoQ10 axis-mediated ferroptosis is involved in sodium aescinate-induced nephrotoxicity.

Sodium aescinate (SA), an active compound found in horse chestnut seeds, is widely used in clinical practice. Recently, the incidence of SA-induced adverse events, particularly renal impairment, has increased. Our previous work demonstrated that SA causes severe nephrotoxicity via nephrocyte ferroptosis; however, the underlying mechanism remains to be fully elucidated. In the current study, we investigated additional molecular pathways involved in SA-induced nephrotoxicity. Our results showed that SA inhibited cell viability, disrupted cellular membrane integrity, and enhanced reactive oxygen species (ROS), ferrous iron (Fe2+), and malondialdehyde (MDA) levels, as well as lipid peroxidation in rat proximal renal tubular epithelial cell line (NRK-52E) cells. SA also depleted coenzyme Q10 (CoQ10, ubiquinone) and nicotinamide adenine dinucleotide (NADH) and reduced ferroptosis suppressor protein 1 (FSP1) and polyprenyltransferase (coenzyme Q2, COQ2) activity, triggering lipid peroxidation and ROS accumulation in mouse kidneys and NRK-52E cells. The overexpression of COQ2, FSP1, or CoQ10 (ubiquinone) supplementation effectively attenuated SA-induced ferroptosis, whereas iFSP1 or 4-formylbenzoic acid (4-CBA) pretreatment exacerbated SA-induced nephrotoxicity. Additionally, SA decreased nuclear factor-erythroid-2-related factor 2 (Nrf2) levels and inhibited Nrf2 binding to the -1170/-1180 bp ARE site in FSP1 promoter, resulting in FSP1 suppression. Overexpression of Nrf2 or its agonist dimethyl fumarate (DMF) promoted FSP1 expression, thereby improving cellular antioxidant capacity and alleviating SA-induced ferroptosis. These results suggest that SA-triggers renal injury through oxidative stress and ferroptosis, driven by the suppression of the Nrf2/FSP1/CoQ10 axis.

Efficient fabrication of bioinspired soft, ridged-slippery surfaces with large-range anisotropic wettability for droplet manipulation.

The droplet lossless directional motion control on slippery surfaces holds immense promise for applications in microfluidic chips, hazardous substance detection, chemical dispensing, etc. However, a significant challenge in this domain lies in efficiently developing soft, slippery surfaces with large-range anisotropic wettability and compatibility for curved scenarios. This study addressed this challenge through a quick 3D printing-assisted method to produce soft, ridged-slippery surfaces (SRSSs) as the droplet manipulation platform. The SRSSs demonstrated substantial anisotropic rolling resistances, measuring 116.9 µN in the perpendicular direction and 7.7 µN in the parallel direction, exhibiting a ratio of 15.2. Combining several extents of anisotropic wettability on a soft substrate could realize diverse reagent manipulation functions. Furthermore, these SRSSs showcased high compatibility with various droplet constituents, impressive liquid impact resistance, self-repair capability, and mechanical durability and thermal durability, ensuring exceptional applicability. As proofs of concept, the SRSSs were successfully applied in droplet control and classification for heavy metal ion detection, mechanical arm-based droplet grab and release, and cross-species transport, showcasing their remarkable versatility, compatibility, and practicality in advanced droplet microfluidic chips and water harvesting applications.

[Experimental study on treatment of retinitis pigmentosa by inducing Müller cell reprogramming with Lycii Fructus and Salviae Miltiorrhizae Radix et Rhizoma].

This study aims to explore the effect of Lycii Fructus and Salviae Miltiorrhizae Radix et Rhizoma(LFSMR), a drug pair possesses the function of nourishing Yin, promoting blood circulation, and brightening the eyes, in treating retinitis pigmentosa(RP)by inhibiting the gliosis of Müller cells(MCs) and inducing their reprogramming and differentiation into various types of retinal nerve cells. Twelve C57 mice were used as the normal control group, and 48 transgenic RP(rd10) mice were randomly divided into the model group, positive control group, and low and high dose LFSMR groups, with 12 mice in each group. HE staining was used to detect pathological changes in the retina, and an electroretinogram was used to detect retinal function. Retinal optical coherence tomography was used to detect retinal thickness and perform fundus photography, and laser speckle perfusion imaging was used to detect local retinal blood flow. Digital PCR was used to detect gene expression related to retinal nerve cells, and immunofluorescence was used to detect protein expression related to retinal nerve cells. LFSMR could significantly improve the pathological changes, increase the amplitude of a and b waves, increase the retinal thickness, restore retinal damage, and increase retinal blood flow in mice with RP lesions. LFSMR could also significantly inhibit the m RNA expression of the glial fibrillary acidic protein( GFAP) during the pathogenesis of RP and upregulate m RNA expression of sex determining region Y box protein 2(SOX2), paired box protein 6(Pax6),rhodopsin, protein kinase C-α(PKCα), syntaxin, and thymic cell antigen 1. 1(Thy1. 1). LFSMR could significantly inhibit GFAP protein expression and enhance protein expression of SOX2, Pax6, rhodopsin, PKCα, syntaxin, and Thy1. 1. It could also reverse the pathological changes in the retina of rd10 mice, improve retinal function and fundus performance, increase retinal thickness, enhance local retinal blood flow, and exert therapeutic effects on RP. The mechanism of action of LFSMR may be related to inhibiting the gliosis of MCs and promoting their reprogramming and differentiation into various types of retinal nerve cells.

Droplet transportation on photosensitive lubricant-impregnated slippery surfaces in response to the light induced Marangoni effect and asymmetrical wetting ridges.

Flexible control of droplet transportation is crucial in various applications but is constrained by liquid-solid friction. The development of biomimetic lubricant-impregnated slippery surfaces provides a new solution for flexible manipulation of droplet transportation. Herein, a light strategy is reported for flexibly controlling droplet transportation on photosensitive lubricant-impregnated slippery surfaces. Owing to the localized heating effect of a focused laser beam via photothermal conversion, the resultant thermal Marangoni flow and horizontal component of the surface tension associated with the asymmetric wetting ridges are together responsible for actuating droplet transportation. It is found that the asymmetry of the wetting ridge is dominated by the thickness of the infused oil layer, which directly affects the droplet transportation. The feasibility of this light strategy is also demonstrated by uphill movement, droplet coalescence, and chemical reaction. This study provides a new design for potential applications in open droplet microfluidics, analytical chemistry, diagnosis, etc.

Myxobolus dumerilii sp. n. (Myxozoa: Myxobolidae) infecting the brain of Chinese longsnout catfish Tachysurus dumerili (Bleeker) in China.

During an investigation of Myxobolus diversity in the Chinese longsnout catfish Tachysurus dumerili (Bleeker), a new species infecting the intracranial epidermis of the host was discovered. Upon opening the cranial cavity, several round whitish plasmodia measuring 0.55-0.80 mm in diameter were observed. Fresh spores (n= 50) were pyriform in the frontal view and fusiform in the sutural view, with a length of 15.4±0.6 (13.9-16.5) µm, width of 9.1±0.4 (8.3-9.8) µm, and thickness of 7.0±0.4 (6.3-7.9) µm. The spores had smooth shell surfaces and transparent membrane sheaths in the posterior. No folds, intercapsular appendix, and caudal appendages were observed. Two equal polar capsules were pyriform and measured 7.5±0.5 (6.7-8.7) µm in length and 3.2±0.3 (2.5-3.6) µm in width. The polar filaments were coiled with five to six turns and perpendicular to the polar capsule length. A BLAST search indicated M. dumerilii sp. n. was closely related to five Myxobolus species (with sequences similarities ranging from 90.54% to 96.52%) found in different organs of yellow catfish Tachysurus fulvidraco (Richardson), rather than the T. dumerili-infecting species M. branchiola Dong and Zhao, 2014 (with 90.5% sequence similarity). Phylogenetic analysis showed that M. dumerilii sp. n. didn't form sister clade with brain-infecting Myxobolus spp, but clustered with M. jianlinensis Gao et Zhao, 2020 and M. voremkhai Akhmerov, 1960 within the Siluriformes-clade with highly supported values, indicating that the host specificity may play a stronger signal than site infections during the evolution of Myxobolus species. Based on the morphological, ecological, and molecular differences observed between the newly discovered species and other available Myxobolus species, M. dumerilii sp. n., is proposed and described in this study.

Light-Fueled Beating Coffee-Ring Deposition for Droplet Evaporative Crystallization.

Condensed deposition favors biochemical analysis, bioassays, and clinical diagnosis, but the existing strategies may suffer from low resolution, inaccurate control, cross-contamination, or miscellaneous apparatus. Herein, we propose a noncontact light strategy to enable the condensed deposition for droplet evaporative crystallization, in which the photothermal effect of a focused infrared laser is employed to induce intense evaporation. Due to the localized heating effect, not only can the droplet evaporative crystallization on the hydrophobic substrate be promoted, but also the resultant intensified Marangoni flow enables the movement of the early-formed crystals, preventing the pinning of the triple-phase contact line. Synergy of the Marangoni flow and nonuniform evaporation makes the solutes tend to accumulate near the focused light beam region, which facilitates the condensed deposition. More importantly, this light strategy not only enables condensed deposition on the hydrophobic surface with low hysteresis, but also works successfully on the hydrophilic substrate with high hysteresis via adjusting input laser power. It is demonstrated that the light strategy proposed in the present study has great potential for relevant applications.

Upper Limit of Light-Levitated Droplet Motion.

The light-enabled droplet levitation shows promising potential in applications in biotechnology, clinical medicine, and nanomaterials. In particular, light-levitated droplets have good followability with a moving laser beam, resulting in flexibility in manipulating their motion. However, it is still unclear whether there exists an upper limit to the light-levitated droplet motion with a moving laser beam. Therefore, the motion of light-levitated droplets above the free interface is studied to determine the upper limit of motions of the droplets with a moving laser beam. We demonstrate that an inefficient interface temperature response because of a very high moving speed of the laser beam and the resultant small upward vertical component of vapor flow are responsible for the existence of an upper-limit velocity. Above the upper limit, the light-levitated droplets are unable to stably move with the laser beam and finally disappear. By contrast, the droplets can stably move with the laser beam in a wide range at or below this upper limit. In addition, an almost linear relationship between the upper-limit velocity of the light-levitated droplets and the input laser power is presented. The findings of the present study are informative for the implementation of this light levitation technology.

Light fueled mixing in open surface droplet microfluidics for rapid probe preparation.

In this study, a contactless, flexible, and interference-free light fueled method has been developed to enhance the mixing between the ssDNA and dynabeads in a droplet, which enables rapid probe preparation for promoting the probe technology based on open surface droplet microfluidics. In this light fueled method, the use of the photothermal effect of a focused infrared laser can easily create non-uniform temperature distribution and accordingly the surface tension gradient over the interface as a result of the localized heating effect, which thereby initiates the Marangoni flow in a droplet. Experimental results confirm that the light-induced Marangoni flow greatly enhances the mixing, ensuring rapid and efficient binding between the ssDNA and dynabeads. Moreover, the mixing intensity and degree can be simply tuned by controlling the laser intensity and laser heating time. The light fueled rapid mixing method developed in the present study paves the way for rapid bio-chemical detection.

NG-STAR genotypes are associated with MDR in Neisseria gonorrhoeae isolates collected in 2017 in Shanghai.

OBJECTIVES: To determine the association of Neisseria gonorrhoeae antimicrobial resistance and genotypes using N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR). METHODS: We characterized 124 N. gonorrhoeae isolates for their antimicrobial susceptibility profiles and NG-STAR ST characteristics using the guidelines of CLSI and EUCAST. The NG-STAR STs of seven loci were analysed. N. gonorrhoeae multiantigen sequence typing (NG-MAST) and MLST analysis was conducted in isolates with specific NG-STAR STs. RESULTS: NG-STAR differentiated 124 N. gonorrhoeae isolates into 84 STs, of which 66 STs were novel to the NG-STAR database. NG-STAR ST-199, ST-348, ST-428, ST-497 and ST-1138 were the predominant STs. Three N. gonorrhoeae isolates with ceftriaxone and cefixime MICs ≥1.0 mg/L were grouped as NG-STAR ST-233. NG-STAR ST-202 isolates (n=4) were associated with high azithromycin MICs and had an identical NG-MAST ST. The NG-STAR ST-348 group (n=5) comprised more isolates with reduced susceptibility to cefixime (n=4) than cefixime-susceptible isolates (n=1). CONCLUSIONS: NG-STAR analysis differentiated N. gonorrhoeae isolates in settings with a high prevalence of antimicrobial resistance. Specific NG-STAR STs are associated with reduced susceptibility to ceftriaxone or cefixime and resistance to azithromycin in N. gonorrhoeae.

Electrochemical modeling and evaluation for textile electrodes to skin.

BACKGROUND: With the development of wearable health-monitoring technologies, a variety of textile electrodes have been produced and applied by researchers. However, there are no universal and effective methods even testing platforms for evaluating the skin-electrode electrochemical interface for textile electrodes because different human bodies have different skin characteristics. METHODS: An electrochemical modeling and evaluation for textile electrodes to skin was proposed, and two electrochemical evaluation platforms (EEP) were set up based on two simulated skin models (SSM). First, skin-electrode electrochemical interface (SEEI) models for traditional wet electrodes and textile electrodes were analyzed. Based on the SEEI models and YY/T 0196-2005 (Chinese YY/T pharmaceutical industry standard for disposable ECG electrode), three skin-electrode electrochemical characteristics (SEEC), including skin-electrode static impedance (SESI), skin-electrode alternating current impedance (SEAI), and skin-electrode polarization voltage (SEPV), were proposed. Then, three electrochemical evaluation methods for textile electrodes to skin were proposed and analyzed, which were the correlation between SEEC and skin-electrode contact pressure (SECP), skin-electrode relative movement (SERM), and conduction loss of active signals (CLAS). Finally, an electrochemical evaluation platform was set up based on an active simulated skin model (ASSM) and passive simulated skin model (PSSM). RESULTS: 9 feature parameters based on the passive electrochemical evaluation platform (PEEP) and 11 feature parameters based on the active electrochemical evaluation platform (AEEP) were obtained for evaluating textile electrodes. And four kinds of textile electrode characteristics including SEEC, SECP, SERM, and CLAS were quantitatively measured based on the electrochemical evaluation platform, and the testing accuracy and range for these characteristics were measured separately. Finally, correlation between SEEC and SECP for 10 kinds of textile electrode samples was studied, and 14 electrochemical characteristics and four skin-electrode contact pressure characteristics were extracted. Experimental results showed that significant correlations were found between six SEEC characteristics and SECP characteristics, and the correlation coefficient between ACI_3 and USECP was the highest. And the polarization voltages of most dry electrode samples showed a downward trend with the increase of contact pressure. CONCLUSIONS: The electrochemical evaluation platform yielded effective experimental data and could provide strong support for the evaluation and application of textile electrodes, which was also effective in evaluating other bioelectric electrodes such as 3M electrode, stainless steel electrode, dry electrode and microneedle electrode.

Identification and characterization of novel anticoagulant peptide with thrombolytic effect and nutrient oligopeptides with high branched chain amino acid from Whitmania pigra protein.

Natural and nutrient substances for cardiovascular disease are promising and capture researchers' minds. Two kinds of novel bioactive peptides (high Fischer's ratio oligopeptides and anticoagulant peptides) were obtained from Whitmania pigra protein via enzymatic hydrolysis. An oligopeptide (MW<874.0 Da) named as HF2 was obtained via chromatography purification procedures with a high Fischer's ratio of 31.92 ± 1.36 and low phenylalanine + tyrosine content of 0.98 ± 0.04 %. Another peptide (WA3-1), prepared by alcalase AF 2.4 L-catalyzed hydrolysis and then purified by DEAE Sepharose FF, gel Sephadex G-15 chromatography, exhibited high anticoagulant activity with prolonging significantly plasma clotting time on activated partial thromboplastin time, prothrombin time, thrombin time (p < 0.01) and powerful thrombolytic activity. Amino acid composition and MALDI-TOF/TOF MS analysis showed that WA3-1 contained 11 amino acids (MW: 1422.0 Da) with the sequence as NH2-His-Asp-Phe-Leu-Asn-Asn-Lys-Leu-Glu-Tyr-Glu-COOH. Abundant negatively charged amino acids in C-terminal, as well as the special residue Lys contribute to its anticoagulant capacity. This research provided a novel natural candidate for the manufacture of nutrient oligopeptides with high branched chain amino acid, and anticoagulant thrombolytic agent in pharmaceutical industry with helping prevent from thrombosis and related cardiovascular diseases.

Sodium aescinate induces renal toxicity by promoting Nrf2/GPX4-mediated ferroptosis.

Sodium aescinate (SA) is extracted from Aesculus wilsonii Rehd seeds and was first marketed as a medicament in German. With the wide application of SA in clinical practice, reports of adverse drug reactions and adverse events have gradually increased, including renal impairment. However, the pathogenic mechanisms of SA have not yet been fully elucidated. The toxic effects and underlying mechanisms of SA were explored in this study. Our data showed that SA significantly elevated the levels of blood urea nitrogen (BUN), serum creatinine (Scr) and Kidney injury molecule 1 (Kim-1), accompanied by pathologically significant changes in renal tissue. SA induced NRK-52E cell death and disrupted the integrity of the cell membrane. Moreover, SA caused significant reductions in FTH, Nrf2, xCT, GPX4, and FSP1 levels, but increased TFR1 and ACSL4 levels. SA decreased glutathione peroxidase (GPx), glutathione (GSH) and cysteine (Cys) levels, but improved Fe2+, malondialdehyde (MDA), reactive oxygen species (ROS) and lipid peroxidation levels, ultimately leading to the induction of ferroptosis. Importantly, inhibition of ferroptosis or activation of the Nrf2/GPX4 pathway prevented SA-induced nephrotoxicity. These findings indicated that SA induced oxidative damage and ferroptosis-mediated kidney injury by suppressing the Nrf2/GPX4 axis activity.

Quercetin inhibits hypertonicity-induced inflammatory injury in human corneal epithelial cells via the PTEN/PI3K/AKT pathway.

Dry eye is a prevalent ophthalmic disease. Ocular surface inflammation in the hyperosmolar environment of the tear film is critical in dry eye progression. Quercetin has strong anti-inflammatory effects; however, its exact mechanism of action in dry eye is not fully understood. Therefore, this study investigated whether quercetin could inhibit the damage sustained to human corneal epithelial cells (HCECs) in a hyperosmolar environment through its anti-inflammatory effects. HCECs were cultured in a complete medium and were divided into four groups: normal, model, quercetin, and inhibitor. The proliferation of HCECs was detected by Ki67 staining; the expression levels of PTEN, p-PI3K and p-AKT were detected by Western blotting and immunofluorescence staining; the relative mRNA expression levels of PTEN, PI3K, AKT, IL-6 and TNF-ɑ were detected by quantitative real-time PCR; the relative expression levels of IL-6 and TNF-α were detected by enzyme-linked immunosorbent assay. In this study, the proliferation of HCECs in the model group was found to be significantly inhibited compared with that in the normal group; however, quercetin was effective in improving the proliferation of HCECs, decreasing the relative expression of p-PI3K, p-AKT, IL-6, TNF-ɑ as well as increasing PTEN. In conclusion, this study demonstrated that quercetin could promote the proliferation of HCECs and reduce the expression of inflammatory factors by inhibiting the PTEN/PI3K/AKT pathway in the hyperosmolarity-induced HCECs model.

Effectiveness of acupuncture combined with artificial tears in managing dry eye syndrome: A systematic review and meta-analysis.

BACKGROUND: Dry eye syndrome is an ocular surface disease with high incidence. Acupuncture combined with artificial tears is effective for treating dry eye syndrome. This study aimed to evaluate the evidence for the efficacy of acupuncture combined with artificial tears in dry eye syndrome by conducting a systematic review and meta-analysis. METHODS: A systematic online search was performed from the date of database establishment to July 1, 2023. The study groups that addressed acupuncture combined with artificial tears for patients with dry eye syndrome (DES) and the control groups that addressed artificial tears were analyzed. The main outcomes were tear breakup time (BUT) and Schirmer I test (SIT), assessed as previously described. RESULTS: Sixteen randomized or controlled trials met the selection criteria, and 1383 patients with DES were included in this study. The analysis results showed that BUT [Standard mean difference (SMD) = 1.25, 95% confidence interval (CI) (1.14, 1.37), P < .0001], SIT [SMD = 1.55, 95% CI (1.08, 2.02), P < .0001], and corneal fluorescein staining [SMD = -2.08, 95% CI (-2.96, -1.20), P < .00001] significantly improved in the trial groups compared with the control groups. The acupuncture treatment was more effective in reducing the levels of IL-6 (P < .0001) and TNF-α (P < .00001). The overall efficacy rate was better in the trial group than in the control group [odds ratio = 4.09, 95% CI (3.04, 5.51), P < .00001]. However, no significant difference was observed in the ocular surface disease index (P = .15) between the trial and control groups. CONCLUSION: The results of this study indicated that acupuncture combined with artificial tears could be considered safe, effective to patients with DES.

HHO optimized support vector machine classifier for traditional Chinese medicine syndrome differentiation of diabetic retinopathy.

AIM: To develop a classifier for traditional Chinese medicine (TCM) syndrome differentiation of diabetic retinopathy (DR), using optimized machine learning algorithms, which can provide the basis for TCM objective and intelligent syndrome differentiation. METHODS: Collated data on real-world DR cases were collected. A variety of machine learning methods were used to construct TCM syndrome classification model, and the best performance was selected as the basic model. Genetic Algorithm (GA) was used for feature selection to obtain the optimal feature combination. Harris Hawk Optimization (HHO) was used for parameter optimization, and a classification model based on feature selection and parameter optimization was constructed. The performance of the model was compared with other optimization algorithms. The models were evaluated with accuracy, precision, recall, and F1 score as indicators. RESULTS: Data on 970 cases that met screening requirements were collected. Support Vector Machine (SVM) was the best basic classification model. The accuracy rate of the model was 82.05%, the precision rate was 82.34%, the recall rate was 81.81%, and the F1 value was 81.76%. After GA screening, the optimal feature combination contained 37 feature values, which was consistent with TCM clinical practice. The model based on optimal combination and SVM (GA_SVM) had an accuracy improvement of 1.92% compared to the basic classifier. SVM model based on HHO and GA optimization (HHO_GA_SVM) had the best performance and convergence speed compared with other optimization algorithms. Compared with the basic classification model, the accuracy was improved by 3.51%. CONCLUSION: HHO and GA optimization can improve the model performance of SVM in TCM syndrome differentiation of DR. It provides a new method and research idea for TCM intelligent assisted syndrome differentiation.

PCa-RadHop: A transparent and lightweight feed-forward method for clinically significant prostate cancer segmentation.

Prostate Cancer is one of the most frequently occurring cancers in men, with a low survival rate if not early diagnosed. PI-RADS reading has a high false positive rate, thus increasing the diagnostic incurred costs and patient discomfort. Deep learning (DL) models achieve a high segmentation performance, although require a large model size and complexity. Also, DL models lack of feature interpretability and are perceived as "black-boxes" in the medical field. PCa-RadHop pipeline is proposed in this work, aiming to provide a more transparent feature extraction process using a linear model. It adopts the recently introduced Green Learning (GL) paradigm, which offers a small model size and low complexity. PCa-RadHop consists of two stages: Stage-1 extracts data-driven radiomics features from the bi-parametric Magnetic Resonance Imaging (bp-MRI) input and predicts an initial heatmap. To reduce the false positive rate, a subsequent stage-2 is introduced to refine the predictions by including more contextual information and radiomics features from each already detected Region of Interest (ROI). Experiments on the largest publicly available dataset, PI-CAI, show a competitive performance standing of the proposed method among other deep DL models, achieving an area under the curve (AUC) of 0.807 among a cohort of 1,000 patients. Moreover, PCa-RadHop maintains orders of magnitude smaller model size and complexity.

Characteristics of different Mandarin pronunciation element perception: evidence based on a multifeature paradigm for recording MMN and P3a components of phonemic changes in speech sounds.

Background: As a tonal language, Mandarin Chinese has the following pronunciation elements for each syllable: the vowel, consonant, tone, duration, and intensity. Revealing the characteristics of auditory-related cortical processing of these different pronunciation elements is interesting. Methods: A Mandarin pronunciation multifeature paradigm was designed, during which a standard stimulus and five different phonemic deviant stimuli were presented. The electroencephalogram (EEG) data were recorded with 256-electrode high-density EEG equipment. Time-domain and source localization analyses were conducted to demonstrate waveform characteristics and locate the sources of the cortical processing of mismatch negativity (MMN) and P3a components following different stimuli. Results: Vowel and consonant differences elicited distinct MMN and P3a components, but tone and duration differences did not. Intensity differences elicited distinct MMN components but not P3a components. For MMN and P3a components, the activated cortical areas were mainly in the frontal-temporal lobe. However, the regions and intensities of the cortical activation were significantly different among the components for the various deviant stimuli. The activated cortical areas of the MMN and P3a components elicited by vowels and consonants seemed to be larger and show more intense activation. Conclusion: The auditory processing centers use different auditory-related cognitive resources when processing different Mandarin pronunciation elements. Vowels and consonants carry more information for speech comprehension; moreover, more neurons in the cortex may be involved in the recognition and cognitive processing of these elements.

Network Pharmacology-Based Identification of Key Targets of Ziyin Mingmu Pills Acting on Age-Related Macular Degeneration.

Objective: This study is designed to find out the molecular targets of effective Chinese medicine Ziyin Mingmu pills (ZMPs) in treating age-related macular degeneration (AMD) based on network pharmacology and experimental data. Methods: A comprehensive network pharmacology strategy that consists of three sequential modules (drug-disease target molecular docking, enrichment analysis, and external verification) was carried out to identify potential targets of ZMPs acting on AMD. Results: The active ingredients of ZMPs targeting 66 genes have effects on the process of AMD. GO and KEGG pathway enrichment analyses suggested that response to oxidative stress, regulation of angiogenesis, and lipid and atherosclerosis might serve as the most important signaling pathways in ZMPs for AMD treatment. Combined with the GSE29801 dataset for further analysis, two key genes, EGFR and VEGFA, were identified. Immune infiltration analysis showed that there was a strong association between EGFR and immune cell content. In addition, images were acquired following 24 h in the scratch experiment showed that ZMPs can reduce the percentage of wound healing distance. The Western blot assay found that ZMPs increased the expression of EGFR and decreased the expression of VEGFA. Conclusion: This study sheds light on some mechanisms of ZMP therapy for AMD, particularly the effect of ZMP on the oxidative stress in RPE and cell survival and angiogenesis in AMD. We propound ZMPs as a promising strategy to intervene in the process of AMD.