Learning the cellular activity representation based on gene regulatory networks for prediction of tumor response to drugs.

Predicting the response of tumor cells to anti-tumor drugs is critical to realizing cancer precision medicine. Currently, most existing methods ignore the regulatory relationships between genes and thus have unsatisfactory predictive performance. In this paper, we propose to predict anti-tumor drug efficacy via learning the activity representation of tumor cells based on a priori knowledge of gene regulation networks (GRNs). Specifically, the method simulates the cellular biosystem by synthesizing a cell-gene activity network and then infers a new low-dimensional activity representation for tumor cells from the raw high-dimensional expression profile. The simulated cell-gene network mainly comprises known gene regulatory networks collected from multiple resources and fuses tumor cells by linking them to hotspot genes that are over- or under-expressed in them. The resulting activity representation could not only reflect the shallow expression profile (hotspot genes) but also mines in-depth information of gene regulation activity in tumor cells before treatment. Finally, we build deep learning models on the activity representation for predicting drug efficacy in tumor cells. Experimental results on the benchmark GDSC dataset demonstrate the superior performance of the proposed method over SOTA methods with the highest AUC of 0.954 in the efficacy label prediction and the best R2 of 0.834 in the regression of half maximal inhibitory concentration (IC50) values, suggesting the potential value of the proposed method in practice.

Non-targeted screening and photolysis transformation of tire-related compounds in roadway runoff.

Roadway runoff serves as a crucial pathway for transporting contaminants of emerging concern (CECs) from urban environments to receiving water bodies. Tire-related compounds originating from tire wear particles (TWPs) have been frequently detected, posing a potential ecological threat. Yet, the photolysis of tire-related compounds within roadway runoff remains inadequately acknowledged. Addressing this deficit, our study utilized high-resolution mass spectrometry (HRMS) to characterize the chemical profile of roadway runoff across eight strategically selected sites in Guangzhou, China. 219 chemicals were identified or detected within different confidence levels. Among them, 29 tire-related contaminants were validated with reference standards, including hexa(methoxymethyl)melamine (HMMM), 1,3-diphenylguanidine (DPG), dicyclohexylurea (DCU), and N-cyclohexyl-2-benzothiazol-amine (DCMA). HMMM exhibited with the abundance ranging from 2.30 × 104-3.10 × 106, followed by DPG, 1.69 × 104-8.34 × 106. Runoff sample were exposed to irradiation of 500 W mercury lamp for photodegradation experiment. Photolysis results indicated that tire-related compounds with a low photolysis rate, notably DCU, DCMA, and DPG, are more likely to persist within the runoff. The photolytic rates were significantly correlated with the spatial distribution patterns of these contaminants. Our findings underscore TWPs as a significant source of pollution in water bodies, emphasizing the need for enhanced environmental monitoring and assessment strategies.

Personalized anti-tumor drug efficacy prediction based on clinical data.

Anti-tumor drug efficacy prediction poses an unprecedented challenge to realizing personalized medicine. This paper proposes to predict personalized anti-tumor drug efficacy based on clinical data. Specifically, we encode the clinical text as numeric vectors featured with hidden topics for patients using Latent Dirichlet Allocation model. Then, to classify patients into two classes, responsive or non-responsive to a drug, drug efficacy predictors are established by machine learning based on the Latent Dirichlet Allocation topic representation. To evaluate the proposed method, we collected and collated clinical records of lung and bowel cancer patients treated with platinum. Experimental results on the data sets show the efficacy and effectiveness of the proposed method, suggesting the potential value of clinical data in cancer precision medicine. We hope that it will promote the research of drug efficacy prediction based on clinical data.

Optimization and verification of selective removal of organophosphate esters from wastewater by molecularly imprinted adsorbent.

Tributyl phosphate (TNBP), a new type of flame retardant, is an emerging pollutant and has been frequently detected in various matrices such as wastewater. Efficient removal of TNBP is critical for wastewater treatment. In this study, molecularly imprinted polymer (MIP) was prepared using precipitation polymerization for selective adsorption of TNBP. The results showed that MIP had a porous structure and formed effective imprinting cavities, which was primarily responsible for its superior adsorption ability. The adsorption of TNBP by MIP was carried out following both the pseudo-secondary kinetic model and the Langmuir isothermal adsorption model. MIP adsorbed TNBP rapidly and reached adsorption equilibrium within 30 min with 923 µmol g-1 at 298 K. The adsorption capacity and adsorption rate of MIP were respectively 2 and 5.49 times those of non-molecularly imprinted polymers. In addition, MIP could effectively counter disturbances from external parameters like temperature and pH, exhibiting strong environmental flexibility. MIP can specifically adsorb organophosphate esters, and can selectively adsorb TNBP under the interference of coexisting contaminants such as1,3-diphenylguanidine and isazofos. In actual bodies of water, MIP's highly selective adsorption of TNBP retains its advantage. The selective adsorption of MIP was mainly due to the common phosphate skeleton, and the specific substituent of organophosphate esters played an important role in the imprinting process. Hydrogen bonding might be involved in the polymerization process of TNBP with acrylamide and the adsorption process of TNBP by MIP.MIP exhibited good reuse efficiency, the total adsorption capacity decreased by no more than 25% after 7 reuse cycles. This study provides a simple and efficient method for selective removal of organophosphate from wastewater.

Dendritic cells in liver transplantation immune response.

Dendritic cells (DCs) are the most powerful antigen presenting cells (APCs), they are considered one of the key regulatory factors in the liver immune system. There is currently much interest in modulating DC function to improve transplant immune response. In liver transplantation, DCs participate in both the promotion and inhibition of the alloreponse by adopting different phenotypes and function. Thus, in this review, we discussed the origin, maturation, migration and pathological effects of several DC subsets, including the conventional DC (cDC), plasmacytoid DC (pDC) and monocyte-derived DC (Mo-DC) in liver transplantation, and we summarized the roles of these DC subsets in liver transplant rejection and tolerance. In addition, we also outlined the latest progress in DC-based related treatment regimens. Overall, our discussion provides a beneficial resource for better understanding the biology of DCs and their manipulation to improve the immune adaptability of patients in transplant status.

Validation of quenching effectiveness and pollutant degradation ability of singlet oxygen through model reaction system.

Quenching method is widely used to assess the contribution of specified reactive species through the probe inhibition efficiency (IE) caused by adding excessive quencher. However, for reactive species with weak ability such as singlet oxygen (1O2), the quenching results are prone to ambiguity. In this study, an 1O2 system using furfuryl alcohol (FFA) as a probe was successfully constructed by methylene-blue-N vis-photosensitization, to discuss the quenching, interference elimination and pollutant degradation ability of 1O2. Inhibition of FFA transformation caused by both quenching and interrupting of 1O2 production was found. The quenching is affected by quencher dosage and ability, which depends on the second-order-rate constant (k). A high k means a strong ability, and less dosage is required to achieve the same IE. Comparison between the calculated ratio of reactive species consumed by quencher and experimental IE helps to judge the interruption of 1O2 production. None of the organic-solvents (methanol, ethanol, iso-propanol, n-butanol, iso-butanol, tert-butanol, tetrahydrofuran, acetonitrile, acetone and chloroform) scavenged 1O2, which would be used as screening-agent for other reactive species (e.g., hydroxyl radicals) that would interrupt 1O2 contribution assessment. Besides, 1O2 was powerless to degrade most selected pollutants. These results encourage proper use of quenchers and better experimental design.

Integrated transcriptomic and metabolomic analysis reveals the response of pearl oyster (Pinctada fucata martensii) to long-term hypoxia.

The frequency at which organisms are exposed to hypoxic conditions in aquatic environments is increasing due to coastal eutrophication and global warming. To reveal the effects of long-term hypoxic stress on metabolic changes of pearl oyster, commonly known as Pinctada (Pinctada fucata martensii), the present study performed the integrated analysis of transcriptomics and metabolomics to investigate the global changes of genes and metabolites following 25 days hypoxia challenge. Transcriptome analysis detected 1108 differentially expressed genes (DEGs) between the control group and the hypoxia group. The gene ontology (GO) analysis of DEGs revealed that they are significantly enriched in functions such as "microtubule-based process", "histone (H3-K4, H3-K27, and H4-K20) trimethylation", "histone H4 acetylation", "kinesin complex", and "ATPase activity", and KEGG pathway functions, such as "DNA replication", "Apoptosis", and "MAPK signaling pathways". Metabolome analysis identified 68 significantly different metabolites from all identified metabolites, and associated with 25 metabolic pathways between the control and hypoxia groups. These pathways included aminoacyl-tRNA biosynthesis, arginine and proline metabolism, and phenylalanine metabolism. Our integrated analysis suggested that pearl oysters were subject to oxidative stress, apoptosis, immune inhibition, and neuronal excitability reduction under long-term hypoxic conditions. We also found a remarkable depression in a variety of biological functions under long-term hypoxia, including metabolic rates, biomineralization activities, and the repression of reorganization of the cytoskeleton and cell metabolism. These findings provide a basis for elucidating the mechanisms used by marine bivalves to cope with long-term hypoxic stress.

Immunomodulatory effects of one novel microRNA miR-63 in pearl oyster Pinctada fucata martensii.

Novel microRNA miR-63 (novel-miR-63) from pearl oyster Pinctada fucata martensii (Pm-novel-miR-63) is a species-specific miRNA. Our previous research has shown that the expression of Pm-novel-miR-63 was significantly downregulated at 24 h after nucleus transplantation. In this study, we analyzed the function and regulatory role of Pm-novel-miR-63 in the immune response of pearl oysters. The results showed that Pm-novel-miR-63 expression increased after the stimulation of pathogen associated molecular patterns at 6-12 h, and the activity of immune and antioxidant enzymes in the serum decreased after Pm-novel-miR-63 overexpression. Transcriptome analysis revealed that Pm-novel-miR-63 participated in regulating transplantation immunity through the Notch and mRNA surveillance signaling pathways. Target prediction and dual luciferase analysis revealed that Pm-GDP-FucTP, Pm-CysLTR2, and Pm-RLR were the target genes of Pm-novel-miR-63. These results suggested that Pm-novel-miR-63 participated in regulating the immune response in pearl oysters and can serve as a new interference target to reasonably control excessive immune rejection in pearl culture.

Enhanced arsenic(III) sequestration via sulfidated zero-valent iron in aerobic conditions: Adsorption and oxidation coupling processes.

Sulfidated zero-valent iron (S-ZVI) has shown significant potential for the removal of arsenic(III). However, little attention has been paid to the mechanism of As(III) sequestration enhancement and how the phase transformation for S-ZVI strengthens this process in aerobic conditions. In this work, sulfidated ZVI was created by ball-milling (S-ZVIbm) and liquid-mixing (S-ZVIlm) of ZVI with elemental sulfur(S0) to investigate the performance and mechanisms of As(III) sequestration in air-saturated water. Sulfidation was found to significantly enhance the As(III) removal rate constant, which was 2.8 âˆ¼ 6.7 times (S-ZVIbm) and 3.1 âˆ¼ 17.1 times (S-ZVIlm) higher than that without sulfidation. FeS was identified as the predominant sulfur species in the S-ZVI samples using S K-edge XANES spectra. The enhanced electron transfer and ZVI corrosion after sulfidation were verified via electrochemical tests. XANES and Mössbauer spectra suggested that lepidocrocite(γ-FeOOH) was the predominant corrosion product generated on the ZVI surface with the presence of oxygen, and DFT calculations further confirmed the improved performance of γ-FeOOH for As(III) sequestration. Besides, As(III) oxidation occurred dominantly on the heterogeneous surface rather than in solution, and the As(III) sequestration pathway of adsorption followed by oxidation was proposed. This study provides new insight into the enhanced As(III) sequestration by S-ZVI in aerobic conditions.

A Review of Intelligent Assembly Technology of Small Electronic Equipment.

Electronic equipment, including phased array radars, satellites, high-performance computers, etc., has been widely used in military and civilian fields. Its importance and significance are self-evident. Electronic equipment has many small components, various functions, and complex structures, making assembly an essential step in the manufacturing process of electronic equipment. In recent years, the traditional assembly methods have had difficulty meeting the increasingly complex assembly needs of military and civilian electronic equipment. With the rapid development of Industry 4.0, emerging intelligent assembly technology is replacing the original "semi-automatic" assembly technology. Aiming at the assembly requirements of small electronic equipment, we first evaluate the existing problems and technical difficulties. Then, we analyze the intelligent assembly technology of electronic equipment from three aspects: visual positioning, path and trajectory planning, and force-position coordination control technology. Further, we describe and summarize the research status and the application of the technology and discuss possible future research directions in the intelligent assembly technology of small electronic equipment.

Oxidation of 1,3-diphenylguanidine (DPG) by goethite activated persulfate: Mechanisms, products identification and reaction sites prediction.

As emerging pollutants continue to be discovered, studies on the degradation behavior of emerging pollutants have proliferated, but few studies have focused on the reactivity of the new pollutants themselves. The work investigated the oxidation of a representative roadway runoff-derived organic contaminant, 1,3-diphenylguanidine (DPG) by goethite activated persulfate (PS). DPG exhibited the highest degradation rate (kd = 0.42 h-1) with present of PS and goethite at pH 5.0, then started to decrease with increasing pH. Chloride ion inhibited DPG degradation by scavenging HO·. Both HO· and SO4-· were generated in goethite activated PS system. Competitive kinetic experiments and flash photolysis experiments were conducted to investigate free radical reaction rate. The second-order reaction rate constants for DPG reacting with HO· and SO4-· were quantified (kDPG + HO·,kDPG + SO4-·), which both reached above 109 M-1 s-1. Chemical structures of five products were identified, four of them were previously detected in DPG photodegradation, bromination and chlorination processes. By density functional theory (DFT) calculations, ortho- and para- C were more easily attacked by both HO· and SO4-·. Abstraction of H on N by HO· and SO4-· were the favorable pathways, and the product TP-210 might be generated by cyclization of DPG radical from abstraction of H on N (3). The results of this study help us to better understand the reactivity of DPG with SO4-· and HO·.

Insight into the application of magnetic molecularly imprinted polymers in soil-washing effluent: Selective removal of 4,4'-dibromodiphenyl ether, high adaptivity of material and efficient recovery of eluent.

Soil washing techniques can effectively remove soil polybrominated diphenyl ethers (PBDEs), but further removal of PBDEs from washing effluent is disrupted by environmental factors and coexisting organic matter. Hence, this work prepared novel magnetic molecularly imprinted polymers (MMIPs) to selectively remove PBDEs in soil washing effluent and recycling surfactants, with Fe3O4 nanoparticles as the magnetic core, methacrylic acid (MAA) as the functional monomer, and ethylene glycol dimethacrylate (EGDMA) as the cross-linker. Later, the prepared MMIPs were applied to adsorb 4,4'-dibromodiphenyl ether (BDE-15) in Triton X-100 soil-washing effluent and characterized by scanning electron microscopy (SEM), infrared spectrometry (FT-IR), nitrogen adsorption and desorption experiments. According to our observations, BDE-15 equilibrium adsorptions on dummy-template magnetic molecularly imprinted adsorbent (D-MMIP, 4-bromo-4'-hydroxyl biphenyl as template) and part-template magnetic molecularly imprinted adsorbent (P-MMIP, toluene as template) were reached within 40 min, and their equilibrium adsorption capacities were 164.54 µmol/g and 145.55 µmol/g, respectively, with imprinted factor α > 2.03, selectivity factor ß > 2.14, and selectivity S > 18.05. MMIPs exhibited good adaptability to pH, temperature, and cosolvent. Our Triton X-100 recovery rate reached as high as 99.9%, and MMIPs maintained a more than 95% adsorption capacity after being recycled five times. Our results offer a novel approach to selectively remove PBDEs in soil-washing effluent, with efficient recovery of surfactants and adsorbents in soil-washing effluent.

Hydrogen-Donor-Controlled Polybrominated Dibenzofuran (PBDF) Formation from Polybrominated Diphenyl Ether (PBDE) Photolysis in Solutions: Competition Mechanisms of Radical-Based Cyclization and Hydrogen Abstraction Reactions.

Polybrominated dibenzofurans (PBDFs) are characteristic dioxin-like products of polybrominated diphenyl ether (PBDE) photolysis. In this study, competition mechanisms of radical-based cyclization and hydrogen abstraction reactions are proposed in PBDF formation. Commonly, the ortho C-Br bond dissociation during photolysis generates aryl radicals, which undergo intramolecular cyclization to form PBDFs or hydrogen abstraction with hydrogen donors (such as organic solvents and water) to form lower brominated PBDEs. By using 2,4,4'-tribromodiphenyl ether (BDE-28) as the model reactant, the experimental PBDF formation ratios in various solutions are explained quantitatively by the calculated rate constants of cyclization and hydrogen abstraction reactions using the density functional theory (DFT) method. The solvent effect of pure and mixed solvents on PBDF formation is illustrated successfully. The structure-related hydrogen donation ability for hydrogen abstraction controls the bias of competition reactions and influences PBDF formation. Water resulted to be the most significant generation of PBDFs. Fulvic and humic acid display higher hydrogen donation ability than small-molecule organics due to the partitioning effect in aqueous solution. Quantitative structure-activity relationship (QSAR) models of the calculated rate constants for 512 cyclization and 319 hydrogen abstraction reactions using 189 PBDEs as the initial reactants in water are established, revealing the high risk of PBDF formation in aqueous solution.

New insight into phytometabolism and phytotoxicity mechanism of widespread plasticizer di (2-ethylhexyl) phthalate in rice plants.

Di-(2-ethylhexyl) phthalate (DEHP) as widely utilized plasticizer has aroused increasing concerns since its endocrine disrupting effects and continuous accumulation in biota. To date, the interaction mechanism between DEHP and rice plants has not been clearly illustrated at molecular level. Here, we investigated biological transformation and response of rice plants (Oryza sativa L.) to DEHP at realistic exposure concentrations. Nontargeted screening by UPLC-QTOF-MS was used to verify 21 transformation products derived from phase I metabolism (hydroxylation and hydrolysis) and phase II metabolism (conjugation with amino acids, glutathione, and carbohydrates) in rice. MEHHP-asp, MEHHP-tyr, MEHHP-ala, MECPP-tyr and MEOHP-tyr as the conjugation products with amino acids are observed for the first time. Transcriptomics analyses unraveled that DEHP exposure had strong negative effects on genes associated with antioxidative components synthesis, DNA binding, nucleotide excision repair, intracellular homeostasis, and anabolism. Untargeted metabolomics revealed that metabolic network reprogramming in rice roots was induced by DEHP, including nucleotide metabolism, carbohydrate metabolism, amino acid synthesis, lipid metabolism, synthesis of antioxidant component, organic acid metabolism and phenylpropanoid biosynthesis. The integrated analyses of interaction between differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs) endorsed that metabolic network regulated by DEGs was significantly interfered by DEHP, resulting in cell dysfunction of roots and visible growth inhibition. Overall, these finding generated fresh perspective for crops security caused by plasticizer pollution and enhanced the public focus on dietary risk.

Identification and comparative analysis of miRNA transcriptomes after allograft and xenograft transplantation in Pinctada fucata martensii.

Effective immune regulation after transplantation during pearl production is crucial for the cultivation of high-quality pearls. MicroRNAs (miRNAs) play an important role in a variety of physiological processes. To understand the regulatory rules of miRNAs after transplantation in Pinctada funcata martensii, we constructed 13 miRNA transcriptomes, including the control group (Con), allograft (Al), and xenograft (Xe) transplantation at six time points (6, 12, and 24 h and 3, 6, and 12 days), in which the xenografted mantle tissue was from Pinctada maxima. We identified 159 differentially expressed miRNAs (DEMs) and found that these DEMs showed high expression at 12 h, 24 h, and 3 days after transplantation. A total of 130 DEMs, such as Let-7, were present in the Al and Xe groups; miR-34 and 16 other DEMs were specifically present in the Al group; miR-216b and 13 other DEMs were specifically present in the Xe group. Compared with the Con group, the target genes of DEMs in the Al group were significantly enriched in protein complex, cytoskeleton, and macromolecular complex, and the Xe group was significantly enriched in ribonucleoside metabolic process, nucleoside binding, and cell division. Compared with the Al group, the target genes in the Xe group were significantly enriched in response to DNA damage stimulation. Overall, multiple pathways associated with cellular activity were enriched in higher numbers of genes in the Xe group than in the Al group. These findings enriched the information on immune regulatory mechanisms at the expression level of miRNAs in P. f. martensii after transplantation.

Balloon Dilation Eustachian Tuboplasty Combined with Tympanotomy Tube Insertion for Treatment of Refractory Otitis Media with Effusion: A Randomized, Prospective, Controlled Trial Comparing Local Anesthesia Combined Sedation Versus General Anesthesia.

BACKGROUND Balloon dilation eustachian tuboplasty (BET) is used to treat eustachian dysfunction but its therapeutic effect and cost-effectiveness when combined with tympanotomy tube insertion (TBI) on refractory otitis media with effusion under local anesthesia with sedation compared to traditional general anesthesia are not well understood. MATERIAL AND METHODS Forty patients with refractory secretory otitis media who received BET+TBI were enrolled in this study and randomized into the local anesthesia with sedation group (n=20) and general anesthesia group (n=20). Tympanometry (TMM), 7-item eustachian tube dysfunction questionnaire (ETDQ-7) results, intraoperative anesthesia accidents, and operation costs were compared between the groups. RESULTS Patients in the local anesthesia with sedation group exhibited intraoperative awareness and pain. Differences in TMM, ETDQ-7 results, and postoperative VAS scores between the groups were comparable (P>0.05). Notably, operative time and treatment costs in the local anesthesia group were lower compared with general anesthesia group. CONCLUSIONS The treatment effects and safety of local anesthesia and general anesthesia under BET combined with TBI for treatment of refractory otitis media with effusion are comparable. However, further studies should aim at reducing pain and discomfort.

Efficient removal of polybrominated diphenyl ethers from soil washing effluent by dummy molecular imprinted adsorbents: Selectivity and mechanisms.

Surfactant enhanced elution is an effective method for removing hydrophobic organic pollutants from soils. The key to the development of leaching technology is selective removal of targeted pollutants in soil washing effluent and recycling of surfactant solutions. In this study, a molecular imprinting technique was applied to selectively sorb polybrominated diphenyl ethers (PBDEs) in soil washing effluent. The novel molecular imprinted polymers (MIPs) using different template molecules were synthesized by precipitation polymerization. Adsorption behaviors and mechanisms of MIPs were studied through experiments and theoretical calculations. The results show that 4-bromo-4'-hydroxybiphenyl and toluene can be effective imprinting molecule for MIPs synthesis. The maximal adsorption capacity of selected dummy molecular imprinted polymer (D1-MIP) was 1032.36 µmol/g, and that of part molecular imprinted polymer (P-MIP) was 981.13 µmol/g. Their imprinting factors in 5 PBDEs adsorption ranged from 2.13 to 5.88, the recovery percentage of Triton X-100 can reach 99.09%, confirming the feasibility of reusing surfactant. Various PBDEs could be removed by MIPs, and Quantitative Structure Property Relationship analysis revealed that PBDEs' molecular volume, planarity, polarity, and hydrophobicity have major influences on their adsorption performance. DFT calculation revealed that Van der Waals force and hydrogen bonding played important roles during selective adsorption. These results can provide effective theoretical guidance for surfactant enhanced soil elution in practical engineering applications.

Delivery of Dexamethasone to the Round Window Niche by Saturated Gelatin Sponge for Refractory Sudden Sensorineural Hearing Loss: A Preliminary Study.

OBJECTIVE: The aim of this study was to evaluate the hearing outcome of dexamethasone sodium phosphate (DSP) delivery to the round window niche by saturated gelatin sponge for refractory sudden sensorineural hearing loss. PATIENTS: Twenty patients with unilateral sudden sensorineural hearing loss with an improvement of pure-tone average (PTA) less than 10 dB after primary systemic treatment with steroids. INTERVENTIONS: Delivery of DSP to the round window niche via saturated sponge gelatin for 2 weeks. MAIN OUTCOME MEASURES: Pure-tone audiometry was taken at the beginning and 4 to 8 weeks after the end of the salvage treatment. RESULTS: PTA thresholds were improved at least 10 dB in 11 of 20 patients (55%) by a mean value of 11.9 dB. The hearing threshold at 500, 1000, and 2000 Hz were improved after salvage treatment, but there was no significant change at 4000 Hz. The PTAs also recovered after the salvage treatment. CONCLUSIONS: Delivery of DSP to the round window niche via saturated gelatin sponge is a simple and feasible way to treat refractory sudden sensorineural hearing loss with a risk of permanent tympanic membrane perforation.

Development and Validation of a Simple Nomogram for Predicting Rapid Myopia Progression in Children with Orthokeratology Management.

PURPOSE: To develop and validate an ideal nomogram and an online calculator for predicting rapid myopia progression risk in children managed with orthokeratology (ortho-k). METHODS: Data of children undergoing ortho-k treatment at Shanghai Children's Hospitals between January 2018 and April 2021 were retrospectively assessed. Potential predictors were screened using univariable analyses and a bidirectional stepwise procedure based on Akaike's information criterion. The final model was constructed using multivariable logistic regression and validated using an internal validation cohort. A nomogram and an online calculator were used to present the final model. RESULTS: In this retrospective study with 1051 eyes of 560 myopia patients, the training cohort included 735 eyes, and the validation cohort included 316 eyes. Among 11 potential predictors of rapid myopia progression considered, the following four variables identified as independent predictive factors were included in the nomogram: age (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.61-0.79), baseline spherical equivalent (OR, 1.53; 95% CI, 1.31-1.79), pupil diameter (OR, 0.56; 95% CI, 0.32-0.97), and horizontal visible iris diameter (OR, 0.57; 95% CI, 0.33-0.97). The mean concordance statistics for the training and validation cohorts were 0.705 (95% CI 0.664-0.747) and 0.707 (95% CI 0.639-0.774), respectively. The online calculator is publicly available (https://hycalculatoronline.shinyapps.io/dynnomapp/). CONCLUSION: This study developed a simple-to-use nomogram and online calculator that predicted rapid myopia progression risk in children treated with ortho-k, who will likely benefit from early intervention and improved surveillance.

Integrated transcriptomic and metabolomic analysis sheds new light on adaptation of Pinctada fucata martensii to short-term hypoxic stress.

Analyses of the transcriptome and metabolome were conducted to clarify alterations of key genes and metabolites in pearl oysters following exposure to short-term hypoxic treatment. We totally detected 209 DEGs between the control and hypoxia groups. Enrichment analysis indicated the enrichment of GO terms including "oxidation-reduction process", "ECM organization", "chaperone cofactor-dependent protein refolding", and "ECM-receptor interaction" KEGG pathway by the DEGs. In addition, between the two groups, a total of 28 SDMs were identified, which were implicated in 13 metabolic pathways, such as "phenylalanine metabolism", "D-amino acid metabolism", and "aminoacyl-tRNA biosynthesis". Results suggest that pearl oysters are exposed to oxidative stress and apoptosis under short-term hypoxia. Also, pearl oysters might adapt to short-term hypoxic treatment by increasing antioxidant activity, modulating immune and biomineralization activities, maintaining protein homeostasis, and reorganizing the cytoskeleton. The results of our study help unveil the mechanisms by which pearl oysters respond adaptively to short-term hypoxia.