Dimension compensation of printed master molds by a desktop LCD 3D printer for high-precision microfluidic applications.

Recent advances in low-cost liquid crystal display (LCD) 3D printing have popularized its use in creating microfluidic master molds and complete devices. However, the quality and precision of these fabrications often fall short of the rigorous standards required for advanced microfluidic applications. This study introduces a novel approach to enhance the dimensional accuracy of microchannels produced using a desktop LCD 3D printer. We propose a method for dimension compensation, optimize the printing parameters, and provide a straightforward post-treatment technique to ensure high-quality curing of polydimethylsiloxane (PDMS) in master molds made from photosensitive resin. Our investigation assesses the precision of 3D printing across three different scales of square cross-section microchannels by measuring their widths and heights, leading to the determination of optimal printing parameters that minimize dimensional errors. The dimensional errors are further reduced by introducing a series of dimension compensation factors, which correct the nominal dimensions of the microchannels by using the compensation factors in 3D printing. The dimensional accuracy is significantly improved after compensation even in fabricating complex microchannels of triangular cross-sections. Finally, a spiral channel of trapezoidal-like cross-section with tilted edges is fabricated for microfluidic application, and highly efficient particle separation is realized in the channel. The proposed method provides new insights for utilizing desktop LCD 3D printers to achieve high-accuracy microstructures necessary for advanced microfluidic applications.

A four-step biosynthetic pathway involving C-3 oxidation-reduction reactions from cycloastragenol to astragaloside IV in Astragalus membranaceus.

Astragaloside IV is a significant chemical component derived from the medicinal plant Astragalus membranaceus. Despite the characterization of several glycosyltransferases from A. membranaceus, the complete biosynthetic pathway of astragaloside IV has not been fully elucidated. In this study, we propose a biosynthetic pathway for astragaloside IV that involves a sequence of oxidation-reduction reactions. The biosynthesis pathway from cycloastragenol to astragaloside IV encompasses four key steps: C-3 oxidation, 6-O-glucosylation, C-3 reduction, and 3-O-xylosylation. We identified a hydroxysteroid dehydrogenase AmHSD1 from A. membranaceus. AmHSD1 catalyzes the C-3 oxidation of cycloastragenol, yielding cycloastragenol-3-one, and the C-3 reduction of cycloastragenol-3-one-6-O-glucoside, resulting in cycloastragenol-6-O-glucoside. Additionally, the glycosyltransferases AmGT8 and AmGT1, previously reported by our groups, were identified as catalyzing the 6-O-glucosylation and 3-O-xylosylation steps, respectively. Astragaloside IV was successfully synthesized in transient expression in Nicotiana benthamiana using the combination of AmHSD1, AmGT8 and AmGT1. These results support the proposed four-step biosynthetic pathway and suggest that AmHSD1 probably plays a crucial role in the biosynthesis of astragaloside IV within A. membranaceus.

Effect of multimorbidity on depressive status in older Chinese adults: evidence from the China Health and Retirement Longitudinal Study (CHARLS).

OBJECTIVE: This study aims to further explore the relevant influencing factors of depression and explore the correlation between multimorbidity coexistence and depression to find the goals and methods of early intervention of depression in the elderly. DESIGN: This study adopts a cross-sectional approach. SETTING: The study population of this project came from the China Health and Retirement Longitudinal Study. Depression was grouped according to the 10-item version of Centre for Epidemiological Research Depression Scale. Chronic diseases, height, weight, grip strength, education, marital status, alcohol consumption, exercise and other indicators were included in the analysis. PARTICIPANTS: 2239 adults over 60 years of age were included. RESULTS: The proportion of women in the depression group was higher (p<0.001). The depression group had a lower grip strength than the control group (p<0.05). The sleep duration was shorter in the depression group (p<0.001). There were differences in education, marital status and alcohol consumption in the depression group (p<0.05). The depression group might have more types of coexisting chronic diseases (p<0.001). The depression group was more likely to have hypertension, dyslipidaemia, chronic lung diseases, heart attack, stroke, stomach disease and memory-related disease. Grip strength was connected with the risk of depression in the elderly (0.971 (95% CI 0.959 to 0.984)). Sleep (0.827 (95% CI 0.785 to 0.872) and education level (0.790 (95% CI 0.662 to 0.942) were related to the risk of depression in the elderly. Concomitant chronic diseases could affect the risk of depression in the elderly (1.455 (95% CI 1.243 to 1.703)). CONCLUSION: The coexistence of multiple chronic diseases and depression is very common in the elderly. The coexistence of multiple chronic diseases is more common in older women and older depressed people. With the increase in the number of chronic diseases, the risk of depression in the elderly is significantly increased.

Acidic Pepsin Affects Laryngeal Carcinoma Cell Growth and Invasion Through Glycolysis.

OBJECTIVE: The pathogenic mechanism underlying the effects of acidic pepsin in laryngeal cancer remains unclear. This study investigated whether acidic pepsin influences Glut-1 expression and glycolytic activity in laryngeal carcinoma cells and whether it plays a role in the growth and migration of these cells through glycolysis. STUDY DESIGN: In vitro study. SETTING: A university-affiliated hospital. METHODS: Laryngeal carcinoma TU 212 and TU 686 cells were treated with acidic pepsin and 2-deoxy-d-glucose (2-DG), then transfected with Glut-1 small interfering RNA (siRNA). Glucose uptake was detected by a radioimmunoassay counter, lactate secretion was detected by a lactic acid kit, and Glut-1 expression was detected by western blotting. Cell viability, migration and invasion, and clonal formation were assessed using the Cell Counting Kit-8, Transwell chamber, and clonal formation assays, respectively. RESULTS: Acidic pepsin significantly increased Glut-1 expression in laryngeal carcinoma cells compared with the control group (P < .01). It also significantly enhanced 18F-fluorodeoxyglucose (Cin/Cout) uptake, lactate secretion, cell viability, migration, invasion, and clonal formation in laryngeal carcinoma cells compared with the control group (P < .01). The glycolytic inhibitor 2-DG and Glut-1 siRNA significantly reversed the effects of acidic pepsin on laryngeal carcinoma cells (P < .01). CONCLUSION: Acidic pepsin enhances the growth and migration of laryngeal carcinoma cells by upregulating Glut-1, thus promoting glycolysis.

HCN channels in the lateral habenula regulate pain and comorbid depressive-like behaviors in mice.

AIMS: Comorbid anxiodepressive-like symptoms (CADS) in chronic pain are closely related to the overactivation of the lateral habenula (LHb). Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have been implicated to play a key role in regulating neuronal excitability. However, the role of HCN channels in the LHb during CADS has not yet been characterized. This study aimed to investigate the effect of HCN channels in the LHb on CADS during chronic pain. METHODS: After chronic neuropathic pain induction by spared nerve injury (SNI), mice underwent a sucrose preference test, forced swimming test, tail suspension test, open-field test, and elevated plus maze test to evaluate their anxiodepressive-like behaviors. Electrophysiological recordings, immunohistochemistry, Western blotting, pharmacological experiments, and virus knockdown strategies were used to investigate the underlying mechanisms. RESULTS: Evident anxiodepressive-like behaviors were observed 6w after the SNI surgery, accompanied by increased neuronal excitability, enhanced HCN channel function, and increased expression of HCN2 isoforms in the LHb. Either pharmacological inhibition or virus knockdown of HCN2 channels significantly reduced LHb neuronal excitability and ameliorated both pain and depressive-like behaviors. CONCLUSION: Our results indicated that the LHb neurons were hyperactive under CADS in chronic pain, and this hyperactivation possibly resulted from the enhanced function of HCN channels and up-regulation of HCN2 isoforms.

Combining metabolomics and transcriptomics to reveal the potential medicinal value of rare species Glycyrrhiza squamulose.

Licorice is a well-known Chinese medicinal plant that is widely used to treat multiple diseases and process food; however, wild licorice is now facing depletion. Therefore, there is an urgent need to identify and protect licorice germplasm diversity. In this study, metabolomic and transcriptomic analyses were conducted to investigate the biodiversity and potential medicinal value of the rare wild Glycyrrhiza squamulose. A total of 182 differentially accumulated metabolites and 395 differentially expressed genes were identified by comparing Glycyrrhiza uralensis and Glycyrrhiza squamulose. The molecular weights of the chemical component of G. squamulose were comparable with those of G. uralensis, suggesting that G. squamulose may have medicinal value. Differentially accumulated metabolites (DAMs), mainly flavonoids such as kaempferol-3-O-galactoside, kaempferol-3-O-(6"malonyl) glucoside, and hispidulin-7-O-glucoside, showed potential vitality in G. squamulose. Comparative transcriptomics with G. uralensis showed that among the 395 differentially expressed genes (DEGs), 69 were enriched in the isoflavonoid biosynthesis pathway. Multiomics analysis showed that the distinction in flavonoid biosynthesis between G. squamulose and G. uralensis was strongly associated with the expression levels of IF7GT and CYP93C. In addition to identifying similarities and differences between G. squamulose and G. uralensis, this study provides a theoretical basis to protect and investigate rare species such as G. squamulose.

Human midbrain dopaminergic progenitors.

Human midbrain dopaminergic progenitors (mDAPs) are one of the most representative cell types in both basic research and clinical applications. However, there are still many challenges for the preparation and quality control of mDAPs, such as the lack of standards. Therefore, the establishment of critical quality attributes and technical specifications for mDAPs is largely needed. "Human midbrain dopaminergic progenitor" jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research, is the first guideline for human mDAPs in China. This standard specifies the technical requirements, test methods, inspection rules, instructions for usage, labelling requirements, packaging requirements, storage requirements, transportation requirements and waste disposal requirements for human mDAPs, which is applicable to the quality control for human mDAPs. It was originally released by the China Society for Cell Biology on 30 August 2022. We hope that the publication of this guideline will facilitate the institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardization of human mDAPs for clinical development and therapeutic applications.

Human neural stem cells.

'Human neural stem cells' jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research, is the first guideline for human neural stem cells (hNSCs) in China. This standard specifies the technical requirements, test methods, test regulations, instructions for use, labelling requirements, packaging requirements, storage requirements, transportation requirements and waste disposal requirements for hNSCs, which is applicable to the quality control for hNSCs. It was originally released by the China Society for Cell Biology on 30 August 2022. We hope that publication of the guideline will facilitate institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardization of hNSCs for clinical development and therapeutic applications.

Chrysin 7-O-ß-D-glucuronide, a dual inhibitor of SARS-CoV-2 3CLpro and PLpro, for the prevention and treatment of COVID-19.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulted in the coronavirus disease 2019 (COVID-19) pandemic. Given the advent of subvariants, there is an urgent need to develop novel drugs. The aim of this study was to find SARS-CoV-2 inhibitors from Scutellaria baicalensis Georgi targeting the proteases 3CLpro and PLpro. After screening 25 flavonoids, chrysin 7-O-ß-D-glucuronide was found to be a potent inhibitor of SARS-CoV-2 on Vero E6 cells, with half-maximal effective concentration of 8.72 µM. Surface plasmon resonance assay, site-directed mutagenesis and enzymatic activity measurements indicated that chrysin-7-O-ß-D-glucuronide inhibits SARS-CoV-2 by binding to H41 of 3CLpro, and K157 and E167 of PLpro. Hydrogen-deuterium exchange mass spectrometry analysis showed that chrysin-7-O-ß-D-glucuronide changes the conformation of PLpro. Finally, chrysin 7-O-ß-D-glucuronide was shown to have anti-inflammatory activity, mainly due to reduction of the levels of the pro-inflammatory cytokines interleukin (IL)-1ß and IL-6.

Clinicopathological features and prognosis analysis of salivary duct carcinoma / 口腔疾病防治

Objective@#To summarize the clinicopathological characteristics and prognostic factors of salivary duct carcinoma (SDC) patients.@*Methods@#This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. The clinical data of 30 SDC patients who were admitted to the Fourth Hospital of Hebei Medical University from 2014 to 2022, including case records, pathological diagnoses, immunohistochemical indicators, treatment methods, follow-up data, and other data, were retrospectively analyzed. SPSS 26.0 software was used to process the data and construct relevant curves. The chi-square test was used to analyze the correlation between different immunohistochemical indices and the recurrence and metastasis of SDC, and a single factor was used to analyze clinical prognostic factors.@*Results@#Among the 30 SDC patients, the male-to-female ratio was 5∶1, with a median age of 61.5 years. Approximately 60% of cases occurred in the parotid gland, whereas the remainder occurred in the submaxillary gland, sublingual gland, or minor salivary gland. Among them, 19 patients were androgen receptor-positive, 23 patients were human epidermal growth factor receptor-2 positive, and 26 patients were Ki-67 positive. Postoperative follow-up was 18-94 months, with a median follow-up of 37 months. There were 13 cases of recurrence and 14 cases of distant metastasis. The 5-year overall survival rate was only 31.2%. The long-term survival of patients who underwent postoperative radiotherapy and chemoradiotherapy was better than that of patients who underwent surgery alone (P= 0.027). T stage and lymph node invasion were associated with prognosis and survival (P<0.05). There was a correlation between a Ki-67-positive cell count ≥ 40% and postoperative recurrence or metastasis (P = 0.025).@*Conclusion@#Radical surgery combined with postoperative radiotherapy and chemoradiotherapy is helpful for improving long-term overall survival, and tumor T stage and lymph node metastasis may be the main factors affecting the prognosis of patients with SDC. Patients with Ki-67-positive cell counts ≥ 40% are prone to postoperative recurrence or metastasis.

Dexmedetomidine attenuates the neuroinflammation and cognitive dysfunction in aged mice by targeting the SNHG14/miR­340/NF­κB axis.

Neuroinflammation plays a key role in the pathogenesis of postoperative cognitive dysfunction (POCD). Results of our previous study demonstrated that dexmedetomidine (Dex) attenuates neuroinflammation in BV2 cells treated with lipopolysaccharide (LPS) by targeting the microRNA (miR)-340/NF-κB axis. However, the molecular mechanisms by which Dex improves POCD remain unclear. In the present study, the association between long non-coding (lnc)RNA small nucleolar RNA host gene 14 (SNHG14) and miR-340 in BV2 microglial cells was determined using a dual-luciferase reporter assay. In addition, SNHG14, miR-340 and NF-κB expression levels were measured in LPS-treated BV-2 cells and hippocampal tissues of mice with POCD, and an enzyme-linked immunosorbent assay was used to determine the levels of proinflammatory mediators. Results of the present study demonstrated that SNHG14 exhibited potential as a target of miR-340. In addition, SNHG14 knockdown increased the levels of miR-340 and reduced the levels of NF-κB in LPS-treated BV2 cells. In addition, Dex treatment significantly reduced the levels of SNHG14 and NF-κB, and elevated the levels of miR-340 in the hippocampus of aged mice with POCD. Moreover, Dex treatment notably decreased the expression levels of TNF-α, IL-1ß, IL-2, IL-6, IL-8 and IL-12 in the hippocampus of aged mice with POCD by upregulating miR-340. The spatial memory impairments in aged mice with POCD were also notably increased following Dex treatment via upregulation of miR-340. Collectively, results of the present study demonstrated that Dex may protect microglia from LPS-induced neuroinflammation in vitro and attenuate hippocampal neuroinflammation in aged mice with POCD in vivo via the SNHG14/miR-340/NF-κB axis. The present study may provide further insights into the mechanisms underlying Dex in the treatment of POCD.

[Effect of sowing dates on physiological characteristics, yield, and quality of Carthamus tinctorius].

A field experiment was conducted to measure the physiological characteristics, yield, active ingredient content, and other indicators of Carthamus tinctorius leaves undergoing 13 sowing date treatments. The principal component analysis(PCA) and redundancy analysis were used to analyze the correlation between these indicators to explore the effect of sowing date on the yield and active ingredient content of C. tinctorius in Liupanshan of Ningxia. The results illustrated that the early sowing in autumn and spring had significant effects on leaf photosynthetic parameters, SPAD value, antioxidant enzyme activity, nitrogen metabolism enzyme activity, filament yield, grain yield, and hydroxy safflower yellow A(HYSA) of C. tinctorius. Sowing in mid-November and late March had the best effect. Leaf transpiration rate, stomatal conductance, nitrate reductase, nitrite reductase, glutamine synthetase, and glutamate synthase increased by 44.9%, 52.4%, 15.9%, 60.8%, 10.3%, and 38.3%, respectively. The activities of superoxide dismutase, peroxidase, and catalase decreased by 10.8%, 4.1%, and 20.9%, respectively. The improvement of photosynthetic physiological characteristics promoted the dry matter accumulation and reproductive growth of C. tinctorius. The yield of filaments and seeds increased by 15.5% and 11.7%, and the yield of HYSA and kaempferol increased by 17.9% and 20.0%. In short, the suitable sowing date can promote the growth and development of C. tinctorius in Liupanshan of Ningxia, and significantly improve the yield and quality, which is conducive to the high quality and efficient production of C. tinctorius.

Regio-specific enzymatic glucosylation of triterpenoids from Antrodia camphorata and their biological activities.

The bacterial glycosyltransferase YjiC1 was used to glycosylate triterpenoids from the medicinal fungus Antrodia camphorata. Eleven new compounds were obtained from enzymatic reactions. Glucosylation could increase the inhibitory activities against COX-2, and improve the anti-inflammatory activities of Antrodia ergostanes on acute lung injury mice, especially (25R)-antcin C 7-O-ß-D-glucoside.

Assessing the Intensity of Marine Biogenic Influence on the Lower Atmosphere: An Insight into the Distribution of Marine Biogenic Aerosols over the Eastern China Seas.

Marine biological activities make a non-negligible contribution to atmospheric aerosols, leading to potential impacts on the regional atmospheric environment and climate. The eastern China seas are highly productive with significant emissions of biogenic substances, but the spatiotemporal variations of marine biogenic aerosols are not well known. Air mass exposure to chlorophyll a (AEC) can be used to indicate the influence of biogenic sources on the atmosphere to a certain degree. In this study, the 12 year (2009-2020) daily AEC were calculated over the eastern China seas, showing the spatial and seasonal patterns of marine biogenic influence intensity which were co-controlled by surface phytoplankton biomass and boundary layer height. By combining the AEC values, relevant meteorological parameters, and extensive observations of a typical biogenic secondary aerosol component, methanesulfonate (MSA), a parameterization scheme for MSA simulation was successfully constructed. This AEC-based approach with observation constraints provides a new insight into the distribution of marine biogenic aerosols. Meanwhile, the wintertime air mass retention over land exhibited a significant decrease, showing a decadal weakening trend of terrestrial transport, which is probably related to the weakening of the East Asian winter monsoon. Thus, marine biogenic aerosols may play an increasingly important role in the studied region.

Base-Modulated 1,3-Regio- and Stereoselective Carboboration of Cyclohexenes.

While chain-walking stimulates wide interest in both polymerization and organic synthesis, site- and stereoselective control of chain-walking on rings is still a challenging task in the realm of organometallic catalysis. Inspired by a controllable chain-walking on cyclohexane rings in olefin polymerization, we have developed a set of chain-walking carboborations of cyclohexenes based on nickel catalysis. Different from the 1,4-trans-selectivity disclosed in polymer science, a high level of 1,3-regio- and cis-stereoselectivity is obtained in our reactions. Mechanistically, we discovery that the base affects the reduction ability of B2 pin2 and different bases lead to different catalytic cycles and different regioselective products (1,2- Vs 1,3-addition). This study provides a concise and modular method for the synthesis of 1,3-disubstituted cyclohexylboron compounds. The incorporation of a readily modifiable boronate group greatly enhances the value of this method, the synthetic potential of which was highlighted by the synthesis of a series of high-valued commercial chemicals and pharmaceutically interesting molecules.

Improving intestinal inflammaging to delay aging? A new perspective.

Greying population is becoming an increasingly critical issue for social development. In advanced aging context, organismal multiple tissues and organs experience a progressive deterioration, initially presenting with functional decline, followed by structural disruption and eventually organ failure. The aging of the gut is one of the key links. Decreased gut function leads to reduced nutrient absorption and can perturb systemic metabolic rates. The degeneration of the intestinal structure causes the migration of harmful components such as pathogens and toxins, inducing pathophysiological changes in other organs through the "brain-gut axis" and "liver-gut axis". There is no accepted singular underlying mechanism of aged gut. While the inflamm-aging theory was first proposed in 2000, the mutual promotion of chronic inflammation and aging has attracted much attention. Numerous studies have established that gut microbiome composition, gut immune function, and gut barrier integrity are involved in the formation of inflammaging in the aging gut. Remarkably, inflammaging additionally drives the development of aging-like phenotypes, such as microbiota dysbiosis and impaired intestinal barrier, via a broad array of inflammatory mediators. Here we demonstrate the mechanisms of inflammaging in the gut and explore whether aging-like phenotypes in the gut can be negated by improving gut inflammaging.

Dexmedetomidine attenuates neuroinflammation and microglia activation in LPS-stimulated BV2 microglia cells through targeting circ-Shank3/miR-140-3p/TLR4 axis.

It has been shown that dexmedetomidine (Dex) could attenuate postoperative cognitive dysfunction (POCD) via targeting circular RNAs (circRNAs). Circ-Shank3 has been found to be involved in the neuroprotective effects of Dex against POCD. However, the role of circ-Shank3 in POCD remains largely unknown. Reverse transcription quantitative PCR (RT-qPCR) was performed to detect circ-Shank3 and miR-140-3p levels in lipopolysaccharide (LPS)-treated microglia BV-2 cells in the absence or presence of Dex. The relationship among circ-Shank3, miR-140-3p and TLR4 was confirmed by dual-luciferase reporter assay. Additionally, Western blot and immunofluorescence (IF) assays were conducted to evaluate TLR4, p65 and Iba-1 or CD11b levels in cells. In this study, we found that Dex notably decreased circ-Shank3 and TLR4 levels and elevated miR-140-3p level in LPS-treated BV2 cells. Mechanistically, circ-Shank3 harbor miR-140-3p, functioning as a miRNA sponge, and then miR-140-3p targeted the 3'-UTR of TLR4. Additionally, Dex treatment significantly reduced TLR4 level and phosphorylation of p65, and decreased the expressions of microglia markers Iba-1 and CD11b in LPS-treated BV2 cells. As expected, silenced circ-Shank3 further reduced TLR4, p65 and Iba-1 and CD11b levels in LPS-treated BV2 cells in the presence of Dex, whereas these phenomena were reversed by miR-140-3p inhibitor. Collectively, our results found that Dex could attenuate the neuroinflammation and microglia activation in BV2 cells exposed to LPS via targeting circ-Shank3/miR-140-3p/TLR4 axis. Our results might shed a new light on the mechanism of Dex for the treatment of POCD.

Pepsin Increases the Proliferation of Vocal Cord Leukoplakia Epithelial Cells by Inducing Autophagy.

OBJECTIVE: To investigate the role of H+ /K+ ATPase in the proliferation of pepsin-induced vocal cord leukoplakia (VCL) cells. STUDY DESIGN: Translation research. SETTING: Affiliated Hospital of University. METHODS: Immunohistochemistry was used to detect pepsin, H+ /K+ ATPase (ATP4A and ATP4B subunits) in VCL cells with varying degrees of dysplasia. After primary cultures of VCL cells had been established, the effects of acidified pepsin on the proliferation, autophagy, and H+ /K+ -ATPase distribution of VCL cells were investigated. RESULTS: The levels of pepsin, ATP4A, and ATP4B were significantly higher in VCL tissue with moderate-to-severe dysplasia than in normal tissue (p < .05); these levels gradually increased according to dysplasia severity. The expression levels of ATP4A and ATP4B were significantly correlated with the amount of pepsin in VCL cells (p < .01). Acidified pepsin enhanced the levels of proliferation and autophagy in human VCL epithelial cells. The cloning- and autophagy-promoting effects of acidified pepsin on VCL cells were partially reversed by pantoprazole; these effects were completely blocked by the autophagy inhibitor chloroquine. Finally, acidified pepsin promoted the colocalization of H+ /K+ -ATPase and lysosomes in VCL cells; it also mediated lysosome acidification. CONCLUSION: Pepsin and H+ /K+ -ATPase may contribute to the progression of VCL. Specifically, acidified pepsin may regulate lysosome acidification by promoting lysosomal localization of H+ /K+ -ATPase.

Improving the identification of miRNA-disease associations with multi-task learning on gene-disease networks.

MicroRNAs (miRNAs) are a family of non-coding RNA molecules with vital roles in regulating gene expression. Although researchers have recognized the importance of miRNAs in the development of human diseases, it is very resource-consuming to use experimental methods for identifying which dysregulated miRNA is associated with a specific disease. To reduce the cost of human effort, a growing body of studies has leveraged computational methods for predicting the potential miRNA-disease associations. However, the extant computational methods usually ignore the crucial mediating role of genes and suffer from the data sparsity problem. To address this limitation, we introduce the multi-task learning technique and develop a new model called MTLMDA (Multi-Task Learning model for predicting potential MicroRNA-Disease Associations). Different from existing models that only learn from the miRNA-disease network, our MTLMDA model exploits both miRNA-disease and gene-disease networks for improving the identification of miRNA-disease associations. To evaluate model performance, we compare our model with competitive baselines on a real-world dataset of experimentally supported miRNA-disease associations. Empirical results show that our model performs best using various performance metrics. We also examine the effectiveness of model components via ablation study and further showcase the predictive power of our model for six types of common cancers. The data and source code are available from https://github.com/qwslle/MTLMDA.

Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation.

Currently, human health due to corona virus disease 2019 (COVID-19) pandemic has been seriously threatened. The coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19. However, the efficacy is compromised by the SARS-CoV-2 evolvement and mutation. Here we report the SARS-CoV-2 S protein receptor-binding domain (RBD) inhibitor licorice-saponin A3 (A3) could widely inhibit RBD of SARS-CoV-2 variants, including Beta, Delta, and Omicron BA.1, XBB and BQ1.1. Furthermore, A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells, with EC50 of 1.016 µM. The mechanism was related with binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis combined with quantum mechanics/molecular mechanics (QM/MM) simulations. Interestingly, phosphoproteomics analysis and multi fluorescent immunohistochemistry (mIHC) respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 MAPK pathways and rebalancing the corresponding immune dysregulation. This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.