Antibacterial Activities and Underlying Mechanisms of the Compound SYAUP-491 against Xanthomonas oryzae pv. oryzae.

SYAUP-491 is a novel alkyl sulfonamide. In this study, in vivo and in vitro tests were performed along with a proteomic analysis to determine the effects and underlying mechanisms of the antibacterial activity of SYAUP-491 against the causative agent of bacterial leaf blight in rice. The antibacterial test results suggested that SYAUP-491 exhibited significant activities against Xanthomonas oryzae pv. oryzae (Xoo) in vitro and in vivo. The minimal EC50 values reached 6.96 µg/mL and the curative activity reached 74.1%. Detailed studies demonstrated that SYAUP-491 altered membrane permeability and caused morphological changes. Based on proteomics results, SYAUP-491 might inhibit bacterial protein synthesis. SYAUP-491 may disrupt and alter cell membrane permeability and could further act on ribosomes in the bacterial body. Given the above results, SYAUP-491 could serve as a new lead compound in the research of antibacterial control of plant pathogenic bacterial disease.

Loss-induced Purcell enhancement in PT-broken whispering gallery microcavities.

Parity-time (PT)-symmetry brings various opportunities for electromagnetic field manipulation and light-matter interaction, such as modification of spontaneous emission. However, previous works mainly focused on the behavior of spontaneous emission at exceptional points or in the PT-symmetry situation. Here, we theoretically demonstrate loss-induced Purcell enhancement in PT-broken whispering gallery microcavities. In the PT-broken phase, one of the supermodes decays slowly thereby playing a leading role in spontaneous emission. As the loss increases, the quality factor of this supermode is higher and the mode volume is smaller, so that the Purcell factors will be larger if the emitter is placed near the lossless cavity. Our findings indicate that loss can enhance the interaction between light and matter, which could be applied to single photon emission, non-Hermitian photonic devices, etc.

Inhibition and enhancement of the spontaneous emission in spherical cavities surrounded by zero-index-materials.

There exist resonance degeneracy and nesting in the spherical dielectric cavity embedded in an infinite zero-index-material (ZIM). However, its spontaneous emission (SE) has been scarcely studied. Here, we investigate the inhibition and enhancement of SE in spherical dielectric cavities surrounded by ZIMs at the nanoscale. In the cavities embedded in ε-near-zero materials, by adjusting the polarization of the emitter, the SE of the emitter can be controlled from inhibition to enhancement, ranging from 10-2 to dozens. For the cavities embedded in µ-near-zero or ε-µ-near-zero materials, the enhancement of SE is also achieved in a large range of cavities. These findings provide more application possibilities in single-photon sources, deformable optical devices with ZIMs, etc.

Role of Orai3-Mediated Store-Operated Calcium Entry in Radiation-Induced Brain Microvascular Endothelial Cell Injury.

Radiation-induced brain injury is a serious complication with complex pathogenesis that may accompany radiotherapy of head and neck tumors. Although studies have shown that calcium (Ca2+) signaling may be involved in the occurrence and development of radiation-induced brain injury, the underlying molecular mechanisms are not well understood. In this study, we used real-time quantitative polymerase chain reaction and Western blotting assays to verify our previous finding using next-generation sequencing that the mRNA and protein expression levels of Orai3 in rat brain microvascular endothelial cells (rBMECs) increased after X-ray irradiation. We next explored the role of Orai3 and Orai3-mediated store-operated Ca2+ entry (SOCE) in radiation-induced brain injury. Primary cultured rBMECs derived from wild-type and Orai3 knockout (Orai3(-/-)) Sprague-Dawley rats were used for in vitro experiments. Orai3-mediated SOCE was significantly increased in rBMECs after X-ray irradiation. However, X-ray irradiation-induced SOCE increase was markedly reduced in Orai3 knockout rBMECs, and the percentage of BTP2 (a nonselective inhibitor of Orai channels)-inhibited SOCE was significantly decreased in Orai3 knockout rBMECs. Functional studies indicated that X-ray irradiation decreased rBMEC proliferation, migration, and tube formation (a model for assessing angiogenesis) but increased rBMEC apoptosis, all of which were ameliorated by BTP2. In addition, occurrences of all four functional deficits were suppressed in X-ray irradiation-exposed rBMECs derived from Orai3(-/-) rats. Cerebrovascular damage caused by whole-brain X-ray irradiation was much less in Orai3(-/-) rats than in wild-type rats. These findings provide evidence that Orai3-mediated SOCE plays an important role in radiation-induced rBMEC damage and brain injury and suggest that Orai3 may warrant development as a potential therapeutic target for reducing or preventing radiation-induced brain injury.

Effects of dietary chenodeoxycholic acid supplementation in a low fishmeal diet on growth performance, lipid metabolism, autophagy and intestinal health of Pacific white shrimp, Litopenaeus vannamei.

An 8-week feeding trial was conducted to evaluate the effects of chenodeoxycholic acid (CDCA) on growth performance, body composition, lipid metabolism, and intestinal health of juvenile white shrimp, Litopenaeus vannamei fed a low fishmeal diet. Four practical diets were formulated: HFM (25% fishmeal), LFM (15% fishmeal), LB1 (LFM + 0.04% CDCA), LB2 (LFM + 0.08% CDCA). Each diet was assigned to four tanks with forty shrimp (initial weight 0.33 ± 0.03 g) per tank. The results indicated that the growth performance of shrimp were similar between the four groups; the crude lipid content of shrimp fed the LB2 diet was significantly lower than those fed the HFM diet (P < 0.05). The lipase activity content in hepatopancreatic were significantly higher in the two CDCA supplemented groups than that in LFM group; the contents of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol in hemolymph were significantly lower in LFM group, LB1 group and LB2 group than that in HFM group (P < 0.05). The shrimp fed LB1 diet was significantly decreased the intestinal expression levels of tube than those fed in HFM diet; the intestinal gene expression of imd and toll were significantly lower in LB2 group than those in HFM group (P < 0.05). The results of hepatopancreas gene expression suggest that shrimp fed the LFM diet showed significantly upregulated expression levels of sterol regulatory element-binding protein (srebp), acetyl-CoA carboxylase (acc), and carnitine palmitoyltransferase 1 (cpt-1) than those fed the HFM diet; shrimp fed the LB1 diet showed significantly upregulated expression levels of srebp, acc, and AMP-activated protein kinase (ampk) than those fed the HFM diet; shrimp fed the LB2 diet had higher expression levels of srebp, acc, and cpt-1 than those fed the HFM diet (P < 0.05). In the hepatopancreas, the shrimp fed the LFM diet shown significantly up-regulated the expression levels of beclin1 compared to those fed HFM diet; the expression levels of autophagy-related protein13 (atg3), autophagy-related protein 12 (atg12) of in shrimp fed the LB1 diet were significantly higher than those fed the HFM diet; and the expression levels of autophagy-related protein13 (atg13), beclin1, atg3, atg12, autophagy-related protein 9 (atg9) of shrimp fed LB2 diet were significantly higher than those fed the HFM diet (P < 0.05). The atg3 in intestine of shrimp fed the LB2 diet were significantly higher than those fed the HFM diet (P < 0.05). Intestinal mucous fold were damaged, hepatic tubules were disorganized and B cells appeared to be swollen in LFM group. The fold height and width of shrimp fed the diets supplemented with CDCA increased significantly than those fed the LFM diet (P < 0.05), the hepatic tubules were neatly arranged, and R cells increased. In conclusion, supplementary CDCA in a low fishmeal diet promoted lipid metabolism, enhanced autophagy of shrimp, also improved the health of the intestine and hepatopancreas.

Design, Synthesis and Structure-Activity Relationship of Novel Pinacolone Sulfonamide Derivatives against Botrytis cinerea as Potent Antifungal Agents.

To develop new fungicides with high efficiency, 46 novel sulfonamide derivatives were designed and synthesized by introducing pinacolone fragment into chesulfamide which was used as lead compound. All compounds were characterized by 1H NMR, 13C NMR, and MS spectra, and the structure of compound P-27 was also confirmed by X-ray single crystal diffraction. It was found that a variety of compounds present excellent inhibitory effect against Botrytis cinerea. The inhibition rates of P-29 on tomato and strawberry were 90.24% (200 mg/L) and 100% (400 mg/L) in vivo respectively, which were better than the lead compound chesulfamide (59.23% on tomato seedlings and 29.63% on strawberries).

miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer.

BACKGROUND: Drug resistance is a major obstacle to successful chemotherapy for epithelial ovarian cancer (EOC). We found a subset of miRNAs associated with the response to first-line platinum-based chemotherapy in EOC by microarray, and miR-206 was one of the most significant miRNAs. The purposes of this study were to evaluate the prognostic and platinum-resistance predictive value of miR-206 in EOC patients and to investigate the functional roles of miR-206 in regulating the platinum resistance of EOC and the underlying mechanism. METHODS: MiRNA expression profiling in EOC specimens was performed using a TaqMan miRNA array. miR-206 expression was confirmed by quantitative real-time PCR (qRT-PCR) analysis. Overexpression of miR-206 in EOC cell lines was achieved by the stable transfection of a recombinant plasmid. In vitro assays of cisplatin cytotoxicity, cell cycle distribution, apoptosis, transwell invasion and cell scratching were employed. Connexin 43 (Cx43) expression was detected by Western blotting. Murine xenograft models were used to determine the effects of miR-206 on platinum resistance in vivo. RESULTS: miR-206 expression was increased in primary platinum-resistant EOC. High miR-206 expression was related to poor prognosis in EOC patients who received platinum-based chemotherapy and predicted chemoresistance to platinum treatment. Overexpression of miR-206 in cisplatin-sensitive EOC cell lines significantly increased cell viability, migration and invasion in the presence of cisplatin and decreased cisplatin-induced apoptosis. Cx43, a target gene of miR-206, was negatively regulated by miR-206 in EOC cell lines and significantly related to better prognosis in patients who received platinum-based chemotherapy (KmPlot). miR-206 had high expression and Cx43 had low expression in platinum-sensitive EOC cell lines compared with resistant ones. In vivo murine xenograft models showed that miR-206 profoundly promoted the chemoresistance of EOC to cisplatin treatment. CONCLUSION: miR-206 was highly expressed in primary platinum-resistant EOCs and functionally promoted platinum resistance in part by downregulating Cx43 expression, thereby providing a useful biomarker for prognostic and platinum-resistance prediction.

PcircRNA_finder: a software for circRNA prediction in plants.

MOTIVATION: Recent studies reveal an important role of non-coding circular RNA (circRNA) in the control of cellular processes. Because of differences in the organization of plant and mammal genomes, the sensitivity and accuracy of circRNA prediction programs using algorithms developed for animals and humans perform poorly for plants. RESULTS: A circRNA prediction software for plants (termed PcircRNA_finder) was developed that is more sensitive in detecting circRNAs than other frequently used programs (such as find_circ and CIRCexplorer), Based on analysis of simulated and real rRNA-/RNAase R RNA-Seq data from Arabidopsis thaliana and rice PcircRNA_finder provides a more comprehensive sensitive, precise prediction method for plants circRNAs. AVAILABILITY AND IMPLEMENTATION: http://ibi.zju.edu.cn/bioinplant/tools/manual.htm CONTACT: fanlj@zju.edu.cnSupplementary information: Supplementary data are available at Bioinformatics online.

5-Hydroxymethylcytosine expression is associated with poor survival in cervical squamous cell carcinoma.

OBJECTIVE: Deoxyribonucleic acid methylation is an important epigenetic modification that is frequently altered in cancer. Recent reports showed that the level of 5-hydroxymethylcytosine was altered in various types of cancers. The influence of deoxyribonucleic acid methylation in cervical squamous cell carcinoma is not fully understood. In this study, we investigated 5-hydroxymethylcytosine and ten-eleven translocation expression in cervical squamous cell carcinoma and whether they are associated with poor survival in cervical squamous cell carcinoma. METHODS: We detected the expression of 5-hydroxymethylcytosine, 5-methylcytosine and TET1/2/3 in 140 patients with cervical squamous cell carcinoma and 40 patients with normal cervical tissues by immunohistochemistry. We assessed the prognostic values of 5-hydroxymethylcytosine, 5-methylcytosine and TET2 in the clinical outcome of cervical squamous cell carcinoma. RESULTS: Expression of 5-hydroxymethylcytosine was significantly decreased in cervical squamous cell carcinoma compared with normal cervix tissues. In contrast, 5-methylcytosine expression was significantly increased in cervical squamous cell carcinoma compared with normal cervix tissues. Moreover, expression of TET2, but not TET1 and TET3, was decreased in cervical squamous cell carcinoma. Our study showed that the decreased level of 5-hydroxymethylcytosine predicts poor prognosis of cervical squamous cell carcinoma patients. The expression of 5-hydroxymethylcytosine was an independent prognostic factor for both disease-free and overall survival of cervical squamous cell carcinoma patients. CONCLUSIONS: In cervical squamous cell carcinoma, less aggressive tumor behavior was correlated with 5-hydroxymethylcytosine and TET2. Our data indicated that 5-hydroxymethylcytosine may become a prognostic marker for cervical squamous cell carcinoma and the decreased expression of TET2 may be an underlying mechanism for decreased 5-hmC in cervical squamous cell carcinoma.

Prognostic values of 5-hmC, 5-mC and TET2 in epithelial ovarian cancer.

PURPOSE: DNA methylation is an important epigenetic modification that is frequently altered in cancer. Recent reports showed that the level of 5-hydroxymethylcytosine (5-hmC) was altered in various types of cancers. The influence of DNA methylation in epithelial ovarian cancer (EOC) is not fully understood. Therefore, the aim of the present study was to investigate factors involved in DNA demethylation in EOC compared with normal ovarian tissues. METHODS: We examined the expression of 5-hmC, 5-mC, and TET2 by immunohistochemistry in 130 cases of EOC and 40 cases of normal ovarian tissues. We assessed the prognostic values of 5-hmC, 5-mC, and TET2 in clinical outcome of EOC. RESULTS: We discovered a significant decrease in 5-hmC and TET2 expression in EOC compared with normal ovarian tissues. In contrast, there was a significant increase in 5-mC expression in EOC compared with normal ovarian tissues. The expression of 5-hmC, 5-mC, and TET2 correlated with pathologic stage, tumor grading, lymph node metastasis, and vascular thrombosis. Furthermore, decreased level of 5-hmC predicts poor prognosis of EOC patients. The expression of 5-hmC was an independent prognostic factor for overall survival of EOC patients. CONCLUSIONS: The data suggest that loss of 5-hmC is an epigenetic event of EOC, and the expression of 5-hmC could serve as a prognostic factor for EOC.

Post-Heat Flexural Properties of Siloxane-Modified Epoxy/Phenolic Composites Reinforced by Glass Fiber.

The post-heat mechanical property is one of the important indices for the fire-resistance evaluation of fiber-reinforced polymers. At present, the primary approach to improving the post-heat mechanical property of a material involves incorporating inorganic fillers; yet, the enhancement is limited, and is accompanied by a reduction in room-temperature performance and processability. This study prepares glass-fiber-reinforced composites with elevated mechanical properties after heat through utilizing two variants of epoxy resins modified with polysiloxane, phenolic resin, kaolin, and graphite. In comparison to the phenolic samples, the phenylpropylsiloxane-modified epoxy resulted in a 115% rise in post-heat flexural strength and a 70% increase in the room-temperature flexural strength of phenolic composites. On the other hand, dimethylsiloxane-modified epoxy leads to a 117% improvement in post-heat flexural strength but a 44% decrease in the room-temperature flexural strength of phenolic composites. Macroscopic/microscopic morphologies and a residual structure model of the composites after heat reveal that, during high temperature exposure, the pyrolysis products of polysiloxane promote interactions between carbon elements and fillers, thus preserving more residues and improving the dimensional stability as well as the density of materials. Consequently, a notable enhancement is observed in both the post-heat flexural strength and the mass of carbon residue after the incorporation of polysiloxane and fillers into the materials. The pyrolysis products of polysiloxane-modified epoxy play a vital role in enhancing the post-heat flexural strength by promoting carbon retention, carbon fixation, and interactions with fillers, offering novel pathways for the development of advanced composites with superior fire-resistance properties.

MiRNA expression signature for potentially predicting the prognosis of ovarian serous carcinoma.

One of the best prognostic predictors for patients with epithelial ovarian cancer is the Federation of Obstetrics and Gynecology (FIGO) stage at diagnosis. Advanced-stage ovarian serous carcinoma (OSC) generally have poor prognosis. The goal of this study is to develop and validate a miRNA expression profile that can differentiate the OSC at early and advanced stages and study its correlation with the prognosis of OSC. To identify a unique microRNA (miRNA) pattern associated with the progression of OSC at early and advanced stages, a miRNA microarray was performed using Chinese tumor bank specimens of patients with OSC stage I or III in a retrospective analysis. The expression of four dysregulated miRNAs was validated using quantitative real-time polymerase chain reaction (qRT-PCR) in an external cohort of 51 cases of OSC samples at stages I and III. Kaplan-Meier analysis was performed to analyze the correlation between the expression of some miRNAs and prognosis. Of the 768 miRNAs analyzed in the microarray, 26 miRNAs were significantly either up- or downregulated, with at least a 2-fold difference, in OSC stage I compared with stage III. The qRT-PCR results showed that miR-510, miR-509-5p, and miR-508-3p were significantly downregulated and that miR-483-5p was upregulated in stage III OSC compared with stage I, which was consistent with the microarray results. Kaplan-Meier analysis showed low miR-510 expression, low miR-509-5p expression, and advanced FIGO stage, and chemotherapy resistance were significantly associated with poorer overall survival (P < 0.05). Our results suggest that miRNAs may play a role in the progression of OSC, and miR-510 and miR-509-5p may be considered novel-candidate clinical biomarkers for predicting OSC outcome.

Rhynchophylline alleviates neuroinflammation and regulates metabolic disorders in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder with limited therapeutic agents. Rhynchophylline (RIN), a tetracyclic oxindole alkaloid isolated from Uncaria rhynchophylla, has multiple neuropharmacological activities, including anti-inflammatory, anti-depression, anti-neurodegenerative disease, and anti-drug addiction. Though it is reported that RIN exerts a neuroprotective effect against PD, the underlying protective mechanism remains obscure. In this study, a mass spectrometry-based metabolomic strategy combined with neurobehavioral tests, serum biochemical assays, and immunohistochemistry were employed to decipher the protective mechanism of RIN against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced subacute PD in mice. Our results indicated that RIN significantly improved the MPTP-induced behavioral abnormalities, reduced the loss of dopaminergic neurons, and reversed the secretion of inflammatory cytokines and oxidative stress indicators. Further studies showed that RIN significantly suppressed the expression of toll-like receptor 4, NOD-like receptor protein 3, and cyclooxygenase 2 in the mouse striatum. The results of serum metabolomics showed that RIN could ameliorate metabolic disorders in PD mainly through the regulation of retinol metabolism, arachidonic acid metabolism, glycerophospholipid metabolism, and purine metabolism. These pieces of evidence revealed that RIN is a promising drug candidate for PD by alleviating neuroinflammation and maintaining metabolic homeostasis.

HealthPrism: A Visual Analytics System for Exploring Children's Physical and Mental Health Profiles with Multimodal Data.

The correlation between children's personal and family characteristics (e.g., demographics and socioeconomic status) and their physical and mental health status has been extensively studied across various research domains, such as public health, medicine, and data science. Such studies can provide insights into the underlying factors affecting children's health and aid in the development of targeted interventions to improve their health outcomes. However, with the availability of multiple data sources, including context data (i.e., the background information of children) and motion data (i.e., sensor data measuring activities of children), new challenges have arisen due to the large-scale, heterogeneous, and multimodal nature of the data. Existing statistical hypothesis-based and learning model-based approaches have been inadequate for comprehensively analyzing the complex correlation between multimodal features and multi-dimensional health outcomes due to the limited information revealed. In this work, we first distill a set of design requirements from multiple levels through conducting a literature review and iteratively interviewing 11 experts from multiple domains (e.g., public health and medicine). Then, we propose HealthPrism, an interactive visual and analytics system for assisting researchers in exploring the importance and influence of various context and motion features on children's health status from multi-levelperspectives. Within HealthPrism, a multimodal learning model with a gate mechanism is proposed for health profiling and cross-modality feature importance comparison. A set of visualization components is designed for experts to explore and understand multimodal data freely. We demonstrate the effectiveness and usability of HealthPrism through quantitative evaluation of the model performance, case studies, and expert interviews in associated domains.

High-Efficiency Simplified Orange and White Organic Light-Emitting Devices Based on a Platinum(II) Complex.

We demonstrated efficient simplified orange and white organic light-emitting devices based on a platinum(II) complex Tetra-Pt-N. The maximum current efficiency achieved from the optimized orange device was 57.6 cd/A. The emission mechanism for the system of Tetra-Pt-N doped into 4,4'-bis(arbazole-9-yl)biphenyl was discussed. Moreover, a high-efficiency and simplified white device was fabricated by introducing an ultra-thin blue phosphorescent emission layer. The white device with a maximum current efficiency of 41.9 cd/A showed excellent stable spectra and low efficiency roll-off.

A Novel Bitcoin and Gold Prices Prediction Method Using an LSTM-P Neural Network Model.

As a result of the fast growth of financial technology and artificial intelligence around the world, quantitative algorithms are now being employed in many classic futures and stock trading, as well as hot digital currency trades, among other applications today. Using the historical price series of Bitcoin and gold from 9/11/2016 to 9/10/2021, we investigate an LSTM-P neural network model for predicting the values of Bitcoin and gold in this research. We first employ a noise reduction approach based on the wavelet transform to smooth the fluctuations of the price data, which has been shown to increase the accuracy of subsequent predictions. Second, we apply a wavelet transform to diminish the influence of high-frequency noise components on prices. Third, in the price prediction model, we develop an optimized LSTM prediction model (LSPM-P) and train it using historical price data for gold and Bitcoin to make accurate predictions. As a consequence of our model, we have a high degree of accuracy when projecting future pricing. In addition, our LSTM-P model outperforms both the conventional LSTM models and other time series forecasting models in terms of accuracy and precision.

Greedy Strategies with Multiobjective Optimization for Investment Portfolio Problem Modeling.

The ultimate purpose of portfolio investment is to reduce investment risk and improve total return on the premise of ensuring reasonable allocation of capital. In this paper, we build a quantitative model to advise on trading based on the price movement of Bitcoin and gold between 2016 and 2021; our goal is to maximize profit while minimizing risk. We mainly use greedy strategies with multiobjective optimization models. For the purpose of obtaining the correct price trend, some popular trend indicator strategies are referred to predict the future price trend in the medium and long term. In addition, we also consider people with different trading preferences and divided them into aggressive, advanced, balanced, and cautious and provided trading strategies for each of these four groups. This gives our model scalability. Finally, we analyze the sensitivity of the model and discuss the impact of trading commission costs on the model results. The model can be applicable to various investment situations.

[Retracted] MicroRNA­466 inhibits the aggressive behaviors of hepatocellular carcinoma by directly targeting metadherin.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the flow cytometric data shown in Figs. 2C, 4C and 5C, and the cell invasion assay data shown in Figs. 2D and E, 4D and E and 5D and E were strikingly similar to data appearing in different form in other articles by different authors. In addition, the authors independently contacted the Editorial Office to request that this paper be retracted owing to the fact that they had not obtained approval from the Ethics Committee of The Second Affiliated Hospital of Harbin Medical University to use the tissue samples, even though they had written that this study was approved by the Ethics Committee, and written informed consent had been provided by all patients enrolled in the research. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Oncology Reports, and the authors' own admission of serious problems concerning the ethical nature of the study, the Editor has decided that this paper should be retracted from the Journal. The authors have agreed to the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 40: 3890­3898, 2018; DOI: 10.3892/or.2018.6763].

Identifying the High-Risk Population for COVID-19 Transmission in Hong Kong Leveraging Explainable Machine Learning.

The worldwide spread of COVID-19 has caused significant damage to people's health and economics. Many works have leveraged machine learning models to facilitate the control and treatment of COVID-19. However, most of them focus on clinical medicine and few on understanding the spatial dynamics of the high-risk population for transmission of COVID-19 in real-world settings. This study aims to investigate the association between population features and COVID-19 transmission risk in Hong Kong, which can help guide the allocation of medical resources and the implementation of preventative measures to control the spread of the pandemic. First, we built machine learning models to predict the number of COVID-19 cases based on the population features of different tertiary planning units (TPUs). Then, we analyzed the distribution of cases and the prediction results to find specific characteristics of TPUs leading to large-scale outbreaks of COVID-19. We further evaluated the importance and influence of various population features on the prediction results using SHAP values to identify indicators for high-risk populations for COVID-19 transmission. The evaluation of COVID-19 cases and the TPU dataset in Hong Kong shows the effectiveness of the proposed methods. The top three most important indicators are identified as people in accommodation and food services, low income, and high population density.

LncRNA UCA1 mediates Cetuximab resistance in Colorectal Cancer via the MiR-495 and HGF/c-MET Pathways.

Background: Cetuximab is one of the most widely used monoclonal antibodies to treat patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC). Unfortunately, cetuximab resistance often occurs during targeted therapy. However, the underlying epigenetic mechanisms remain unclear. Our previous study demonstrated that the exosomal transfer of urothelial carcinoma-associated 1 (UCA1) confers cetuximab resistance to CRC cells. The goal of this study was to elucidate the detailed role of UCA1 in cetuximab resistance in CRC and the underlying molecular mechanism. Methods: In vitro and in vivo functional studies were performed to assess the role of UCA1 in cetuximab resistance in CRC cell lines and xenograft models. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to examine UCA1 localization and expression. Bioinformatics analysis was performed to predict the potential mechanism of UCA1, which was further validated by the dual-luciferase reporter assay and the RNA immunoprecipitation (RIP) assay. Cells treated with indicators were subjected to Cell Counting Kit-8 (CCK-8) and western blotting to investigate the role of hepatocyte growth factor (HGF)/c-mesenchymal-epithelial transition (c-MET) signalling in UCA1-mediated cetuximab resistance. Results: We showed that UCA1 decreased CRC cell sensitivity to cetuximab by suppressing apoptosis. Mechanistic studies revealed that UCA1 promoted cetuximab resistance by competitively binding miR-495 to facilitate HGF and c-MET expression in CRC cells. Moreover, HGF was shown to attenuate the cetuximab-induced inhibition of cell proliferation by activating the HGF/c-MET pathway in CRC cells. Conclusion: We provide the first evidence of a UCA1-miR-495-HGF/c-MET regulatory network involved in cetuximab resistance in CRC. Therefore, UCA1 has potential as a predictor and therapeutic target for cetuximab resistance.