The dose-response relationship of vortioxetine on major depressive disorder: an umbrella review.

Vortioxetine is a novel multimodal antidepressant, but its precise efficacy and dose-response relationship for treating different symptoms in major depressive disorder (MDD) is still unclear. This umbrella review aims to assess the effectiveness, tolerability, and dose-response relationship of vortioxetine across a comprehensive range of clinical features in adults with MDD, including cognition, depression, anxiety, quality of life, and side effects. We meticulously searched eight electronic databases and included systematic reviews (SRs) and meta-analyses (MAs) of vortioxetine. The methodological quality of each included SR was independently assessed using the AMSTAR2 tool. To evaluate the credibility of the evidence, we utilized the GRADE framework and the Ioannidis criteria. In total, 35 SRs with 278 MAs met the inclusion criteria and based on these studies we performed 56 MAs of interest. While vortioxetine has been consistently shown to have positive effects on various domains, the evidence regarding cognitive performance and depression symptoms is notably robust compared to placebo, despite of relatively overall low quality of evidence. Finally, a dose-response relationship was observed across all categories within the treatment range of 5-20 mg/d and a dosage of vortioxetine 20 mg/d is recommended for adult MDD patients to achieve full functional recovery.

Substantial increase in perfluorocarbons CF4 (PFC-14) and C2F6 (PFC-116) emissions in China.

The perfluorocarbons tetrafluoromethane (CF4, PFC-14) and hexafluoroethane (C2F6, PFC-116) are potent greenhouse gases with near-permanent atmospheric lifetimes relative to human timescales and global warming potentials thousands of times that of CO2. Using long-term atmospheric observations from a Chinese network and an inverse modeling approach (top-down method), we determined that CF4 emissions in China increased from 4.7 (4.2-5.0, 68% uncertainty interval) Gg y-1 in 2012 to 8.3 (7.7-8.9) Gg y-1 in 2021, and C2F6 emissions in China increased from 0.74 (0.66-0.80) Gg y-1 in 2011 to 1.32 (1.24-1.40) Gg y-1 in 2021, both increasing by approximately 78%. Combined emissions of CF4 and C2F6 in China reached 78 Mt CO2-eq in 2021. The absolute increase in emissions of each substance in China between 2011-2012 and 2017-2020 was similar to (for CF4), or greater than (for C2F6), the respective absolute increase in global emissions over the same period. Substantial CF4 and C2F6 emissions were identified in the less-populated western regions of China, probably due to emissions from the expanding aluminum industry in these resource-intensive regions. It is likely that the aluminum industry dominates CF4 emissions in China, while the aluminum and semiconductor industries both contribute to C2F6 emissions. Based on atmospheric observations, this study validates the emission magnitudes reported in national bottom-up inventories and provides insights into detailed spatial distributions and emission sources beyond what is reported in national bottom-up inventories.

Rising Perfluorocyclobutane (PFC-318, c-C4F8) Emissions in China from 2011 to 2020 Inferred from Atmospheric Observations.

Global atmospheric emissions of perfluorocyclobutane (c-C4F8, PFC-318), a potent greenhouse gas, have increased rapidly in recent years. Combining atmospheric observations made at nine Chinese sites with a Lagrangian dispersion model-based Bayesian inversion technique, we show that PFC-318 emissions in China grew by approximately 70% from 2011 to 2020, rising from 0.65 (0.54-0.72) Gg year-1 in 2011 to 1.12 (1.05-1.19) Gg year-1 in 2020. The PFC-318 emission increase from China played a substantial role in the overall increase in global emissions during the study period, contributing 58% to the global total emission increase. This growth predominantly originated in eastern China. The regions with high emissions of PFC-318 in China overlap with areas densely populated with polytetrafluoroethylene (PTFE) factories, implying that fluoropolymer factories are important sources of PFC-318 emissions in China. Our investigation reveals an emission factor of approximately 3.02 g of byproduct PFC-318 emissions per kg of hydrochlorofluorocarbon-22 (HCFC-22) feedstock use in the production of tetrafluoroethylene (TFE) (for PTFE production) and hexafluoropropylene (HFP) if we assume all HCFC-22 produced for feedstock uses in China are pyrolyzed to produce PTFE and HFP. Further facility-level sampling and analysis are needed for a more precise evaluation of emissions from these factories.

Functional analysis of a novel intronic variant of MCPH1 with autosomal recessive primary microcephaly.

Autosomal Recurrent Primary Microscopic (MCPH, OMIM: 251200) is a neurodevelopmental disorder that is characterized by a noticeable decrease in brain size, particularly in the cerebral cortex, but with a normal brain structure and a non-progressive intellectual disability. MCPH1 has been identified as the gene that triggers primary microcephaly (MCPH1，OMIM: 607117). Here we report a case of autosomal recessive primary microcephaly as caused by a novel variant in the MCPH1 gene. Head circumference was measured by Magnetic Resonance Imaging (MRI), while the Wechsler Intelligence Scale was used to evaluate the intelligence of the individual being tested. B-ultrasound was used to assess gonadal development, and semen routine was used to assess sperm status. The whole-exome sequencing (WES) was performed on the proband. Sanger sequencing was conducted on the parents of the proband to determine if the novel variant in the MCPH1 gene was present. The effect of the mutation on the splicing of MCPH1 was verified by minigene approach. It was observed that the proband had autosomal recessive primary microcephaly and azoospermatism. A novel splice-site homozygous mutation (c.233+2T > G) of the MCPH1 gene was identified, which inherited from his parents. Minigene approach confirmed that c.233+2T > G could affect the splicing of MCPH1. Therefore, our findings contributed to the mutation spectrum of the MCPH1 gene and may be useful in the diagnosis and gene therapy of MCPH.

Di-n-butyl phthalate induces toxicity in male fetal mouse testicular development by regulating the MAPK signaling pathway.

"White pollution" has a significant impact on male reproduction. Di-n-butyl phthalate (DBP) is one of the most important factors in this type of pollution. Currently, research from international sources has demonstrated the significant reproductive toxicity of DBP. However, most of these studies have focused mainly on hormones expression at the protein and mRNA levels and the specific molecular targets of DBP and its mechanisms of action remain unclear. In this study, we established a Sprague Dawley pregnant mouse model exposed to DBP, and all male offspring were immediately euthanized at birth and bilateral testes were collected. We found through transcriptome sequencing that cell apoptosis and MAPK signaling pathway are the main potential pathways for DBP induced reproductive toxicity. Molecular biology analyses revealed a significant increase in the protein levels of JNK1(MAPK8) and BAX, as well as a significant increase in the BAX/BCL2 ratio after DBP exposure. Therefore, we propose that DBP induces reproductive toxicity by regulating JNK1 expression to activate the MAPK signaling pathway and induce reproductive cell apoptosis. In conclusion, our study provides the first evidence that the MAPK signaling pathway is involved in DBP-induced reproductive toxicity and highlights the importance of JNK1 as a potential target of DBP in inducing reproductive toxicity.

Sustained growth of sulfur hexafluoride emissions in China inferred from atmospheric observations.

Sulfur hexafluoride (SF6) is a potent greenhouse gas. Here we use long-term atmospheric observations to determine SF6 emissions from China between 2011 and 2021, which are used to evaluate the Chinese national SF6 emission inventory and to better understand the global SF6 budget. SF6 emissions in China substantially increased from 2.6 (2.3-2.7, 68% uncertainty) Gg yr-1 in 2011 to 5.1 (4.8-5.4) Gg yr-1 in 2021. The increase from China is larger than the global total emissions rise, implying that it has offset falling emissions from other countries. Emissions in the less-populated western regions of China, which have potentially not been well quantified in previous measurement-based estimates, contribute significantly to the national SF6 emissions, likely due to substantial power generation and transmission in that area. The CO2-eq emissions of SF6 in China in 2021 were 125 (117-132) million tonnes (Mt), comparable to the national total CO2 emissions of several countries such as the Netherlands or Nigeria. The increasing SF6 emissions offset some of the CO2 reductions achieved through transitioning to renewable energy in the power industry, and might hinder progress towards achieving China's goal of carbon neutrality by 2060 if no concrete control measures are implemented.

[Retracted] Correlation of SOX9 and NM23 genes with the incidence and prognosis of prostate cancer.

[This retracts the article DOI: 10.3892/ol.2018.9828.].

A novel contact force sensing pulsed field ablation catheter in a porcine model.

BACKGROUND: Pulsed field ablation (PFA) has emerged as a novel non-thermal modality with highly myocardium-specific. However, the PFA catheter based on contact force (CF)-sensing has not been reported. The study aimed to evaluate the efficacy and safety of a novel CF-sensing PFA catheter. METHODS: First, different CF (5, 15, 25, and 35 g) of the novel PFA catheter were evaluated on lesion dimensions during ablation on right and left ventricle in two pigs. Next, this catheter was further evaluated on four typical sites of superior vena cava (SVC), cavotricuspid isthmus (CTI), right superior pulmonary vein (RSPV), and right inferior pulmonary vein (RIPV) for atrial ablation in another six pigs. Electrical isolation was evaluated immediately after ablation and 30-day survival. Chronic lesions were assessed via histopathology after euthanasia. Acute and chronic safety outcomes were observed peri- and post-procedurally. RESULTS: In ventricular ablation, increased CF from 5 to 15 g produced significantly greater lesion depth but nonsignificant increases from 15 to 35 g. In atrial ablation, the novel CF-sensing PFA deliveries produced an acute attenuation of local electrograms and formation of a continuous line of block in all 6 pigs. The ablation line remained sustained blockage at the 30-day survival period. The CF of SVC, CTI, RSPV, and RIPV was 9.4 ± 1.5, 14.5 ± 3.2, 17.2 ± 2.6, and 13.4 ± 2.8 g, respectively. Moreover, no evidence of damage to esophagus or phrenic nerve was observed. CONCLUSION: The novel CF-sensing PFA catheter potentiated efficient, safe, and durable ablation, without causing damage to the esophagus or phrenic nerve.

Antifungal activity and potential mechanism of action of Huangqin decoction against Trichophyton rubrum.

Introduction. Trichophyton rubrum is a major causative agent of superficial dermatomycoses such as onychomycosis and tinea pedis. Huangqin decoction (HQD), as a classical traditional Chinese medicine formula, was found to inhibit the growth of common clinical dermatophytes such as T. rubrum in our previous drug susceptibility experiments.Hypothesis/Gap Statement. The antifungal activity and potential mechanism of HQD against T. rubrum have not yet been investigated.Aim. The aim of this study was to investigate the antifungal activity and explore the potential mechanism of action of HQD against T. rubrum.Methodology. The present study was performed to evaluate the antifungal activity of HQD against T. rubrum by determination of minimal inhibitory concentrations (MICs), minimal fungicidal concentrations (MFCs), mycelial growth, biomass, spore germination and structural damage, and explore its preliminary anti-dermatophyte mechanisms by sorbitol and ergosterol assay, HPLC-based ergosterol test, enzyme-linked immunosorbent assay and mitochondrial enzyme activity test.Results. HQD was able to inhibit the growth of T. rubrum significantly, with an MIC of 3.125 mg ml-1 and an MFC of 12.5 mg ml-1. It also significantly inhibited the hyphal growth, conidia germination and biomass growth of T. rubrum in a dose-dependent manner, and induced structural damage in different degrees for T. rubrum cells. HQD showed no effect on cell wall integrity, but was able to damage the cell membrane of T. rubrum by interfering with ergosterol biosynthesis, involving the reduction of squalene epoxidase (SE) and sterol 14α-demethylase P450 (CYP51) activities, and also affect the malate dehydrogenase (MDH), succinate dehydrogenase (SDH) and ATPase activities of mitochondria.Conclusion. These results revealed that HQD had significant anti-dermatophyte activity, which was associated with destroying the cell membrane and affecting the enzyme activities of mitochondria.

Erratum: Development of a gene edited next-generation hematopoietic cell transplant to enable acute myeloid leukemia treatment by solving off-tumor toxicity.

[This corrects the article DOI: 10.1016/j.omtm.2023.101135.].

Inverse Modeling Revealed Reversed Trends in HCFC-141b Emissions for China during 2018-2020.

Having the highest ozone-depleting potential among hydrochlorofluorocarbons (HCFCs), the production and consumption of HCFC-141b (1,1-dichloro-1-fluoroethane, CH3CCl2F) are controlled by the Montreal Protocol. A renewed rise in global HCFC-141b emissions was found during 2017-2020; however, the latest changes in emissions across China are unclear for this period. This study used the FLEXible PARTicle dispersion model and the Bayesian framework to quantify HCFC-141b emissions based on atmospheric measurements from more sites across China than those used in previous studies. Results show that the estimated HCFC-141b emissions during 2018-2020 were on average 19.4 (17.3-21.6) Gg year-1, which was 3.9 (0.9-7.0) Gg year-1 higher than those in 2017 (15.5 [13.4-17.6] Gg year-1), showing a renewed rise. The proportion of global emissions that could not be exactly traced in 2020 was reduced from about 70% reported in previous studies to 46% herein. This study reconciled the global emission rise of 3.0 ± 1.2 Gg year-1 (emissions in 2020 - emissions in 2017): China's HCFC-141b emissions changed by 4.3 ± 4.5 Gg year-1, and the combined emissions from North Korea, South Korea, western Japan, Australia, northwestern Europe, and the United States changed by -2.2 ± 2.6 Gg year-1, while those from other countries/regions changed by 0.9 ± 5.3 Gg year-1.

Development of a gene edited next-generation hematopoietic cell transplant to enable acute myeloid leukemia treatment by solving off-tumor toxicity.

Immunotherapy of acute myeloid leukemia (AML) has been challenging because the lack of tumor-specific antigens results in "on-target, off-tumor" toxicity. To unlock the full potential of AML therapies, we used CRISPR-Cas9 to genetically ablate the myeloid protein CD33 from healthy donor hematopoietic stem and progenitor cells (HSPCs), creating tremtelectogene empogeditemcel (trem-cel). Trem-cel is a HSPC transplant product designed to provide a reconstituted hematopoietic compartment that is resistant to anti-CD33 drug cytotoxicity. Here, we describe preclinical studies and process development of clinical-scale manufacturing of trem-cel. Preclinical data showed proof-of-concept with loss of CD33 surface protein and no impact on myeloid cell differentiation or function. At clinical scale, trem-cel could be manufactured reproducibly, routinely achieving >70% CD33 editing with no effect on cell viability, differentiation, and function. Trem-cel pharmacology studies using mouse xenograft models showed long-term engraftment, multilineage differentiation, and persistence of gene editing. Toxicology assessment revealed no adverse findings, and no significant or reproducible off-target editing events. Importantly, CD33-knockout myeloid cells were resistant to the CD33-targeted agent gemtuzumab ozogamicin in vitro and in vivo. These studies supported the initiation of the first-in-human, multicenter clinical trial evaluating the safety and efficacy of trem-cel in patients with AML (NCT04849910).

Anthropogenic Chloroform Emissions from China Drive Changes in Global Emissions.

Emissions of chloroform (CHCl3), a short-lived halogenated substance not currently controlled under the Montreal Protocol on Substances that Deplete the Ozone Layer, are offsetting some of the achievements of the Montreal Protocol. In this study, emissions of CHCl3 from China were derived by atmospheric measurement-based "top-down" inverse modeling and a sector-based "bottom-up" inventory method. Top-down CHCl3 emissions grew from 78 (72-83) Gg yr-1 in 2011 to a maximum of 193 (178-204) Gg yr-1 in 2017, followed by a decrease to 147 (138-154) Gg yr-1 in 2018, after which emissions remained relatively constant through 2020. The changes in emissions from China could explain all of the global changes during the study period. The CHCl3 emissions in China were dominated by anthropogenic sources, such as byproduct emissions during disinfection and leakage from chloromethane industries. Had emissions continued to grow at the rate observed up to 2017, a delay of several years in Antarctic ozone layer recovery could have occurred. However, this delay will be largely avoided if global CHCl3 emissions remain relatively constant in the future, as they have between 2018 and 2020.

Effect of Training on the Ability of Nurses to Provide Humanistic Care: Systematic Review and Meta-analysis.

BACKGROUND: This article describes a systematic review evaluating the effectiveness of training on the humanistic care abilities of nurses. METHOD: The literature search was conducted in electronic databases to identify studies that evaluated the effect of training on the humanistic care abilities of nurses. Study selection was based on precise eligibility criteria. After the systematic review, a meta-analysis of standardized mean differences (SMDs) between posttraining and pretraining humanistic care scale scores was performed to evaluate the effect of training. RESULTS: A total of 11 studies were included (624 nurse participants; 97% women; weighted average age = 38.4 years; 95% confidence interval (CI) [31.5, 45.4]). Training schedules varied and ranged from a full-day workshop to brief weekly sessions for up to 2 months. The training framework involved compassion and empathy communication in most of the included studies. Training improved the humanistic care scale scores of the participants (SMD = 1.171; 95% CI [0.626, 1.716]; p < .0001), whereas no significant change was seen in the scores of control subjects (SMD = 0.588; 95% CI [-0.536, 1.713]; p = .305). The effect of training was observable for up to 1 year, although few studies carried out follow-up evaluations. CONCLUSION: Training has the potential to improve the humanistic care abilities of nurses. [J Contin Educ Nurs. 2023;54(9):430-436.].

One health genomic insights into the host-specific evolution and cross-host transmission of Staphylococcus aureus in animal farm environments, food of animal origin, and humans.

OBJECTIVES: Staphylococcus aureus is an opportunistic pathogen that is considered a high priority for research. However, comparative studies of S. aureus strains from different environments and hosts are still lacking. METHODS: Here, we performed a high-resolution bioinformatics analysis of 576 S. aureus genomes isolated from livestock, farm environments, farm workers, animal-origin food, and humans. RESULTS: The S. aureus isolates showed high diversity in genetic lineages and demonstrated host specialization and multi-host range in the population phylogeny. Recent transmission events, historical divergences, and frequent host switching in specific sequence types (STs) and through the food chain and animal farm mediums were observed. Frequent gene transfer may quickly give rise to new fitness to colonize their host or switch to other hosts, even in isolates with the closest vertical evolutionary history. The large multi-host-shared antibiotic resistance gene (ARG) pool was the major factor shaping antibiotic resistance in S. aureus isolates. We revealed the genetic backgrounds of mec, cfr, and optrA, which could be spread among isolates from different species, hosts, and environments. CONCLUSION: Overall, our findings provide One Health genomic insights into the evolution, transmission, gene content characteristics, and antibiotic resistance profiles of S. aureus from different hosts, suggesting that, despite well-formed host specificity during the evolution of S. aureus, the ever-expanding host range and the cross-hosts/niches transmission (at both the strain and genetic level) may be facilitated by diverse bacterial vehicles (e.g., food chain, farm environments, and workers), which will lead to emerging antibiotic resistance consequences and threaten public health and food safety.

Zero-Dimensional Ignition Model of Boron Agglomerates.

Boron primarily exists in the form of agglomerates in ramjet combustion chambers. However, the model used to predict the ignition time of boron agglomerates is usually based on the single-particle assumption, resulting in inaccurate predictions. This study aims to develop a numerical model that can accurately describe the ignition of boron agglomerates. The model is based on the ignition model of a single particle boron proposed by the group of Kuo. Thiele modulus and effectiveness factor are introduced to represent the diffusion resistance of reaction gases in the pores of boron agglomerates. The model includes the necessary physical processes to accurately predict the ignition time. The rates of evaporation and heterogeneous reactions involved in the oxide layer removal process are corrected based on the fact that the diffusion rate of (BO)n in the liquid oxide layer equals to its consumption rate at the oxide-air interface. To evaluate the accuracy of the model, the obtained results for ignition time are compared with experimental data, showing reasonable consistency between them. The model is then applied to investigate the ignition characteristics of boron agglomerates. Parameters, such as initial average pore diameter, oxide layer thicknesses, initial particle diameter, O2 concentration, H2O concentration, and environmental pressure, are studied for their effects on the ignition time. In summary, the boron ignition model established in this study is a powerful tool to investigate the ignition mechanisms and characteristics of boron agglomerates. It can be further coupled with flow analysis for the detailed simulation of turbulent combustion in ramjet combustors.

In Situ Observations of Halogenated Gases at the Shangdianzi Background Station and Emission Estimates for Northern China.

Halogenated gases include ozone-depleting substances and greenhouse gases, such as chlorofluorocarbons, halons, hydrochlorofluorocarbons, hydrofluorocarbons, and perfluorinated gases. In situ atmospheric observations of major halogenated gases were conducted at the Shangdianzi (SDZ) background station, China, from October 2020 to September 2021 using ODS5-pro, a newly developed measurement system. The measurement time series of 36 halogenated gases showed occasional pollution events, where background conditions represented 25% (CH2Cl2) to 81% (CF3Cl, CFC-13) of the measurements. The annual mean background mole fractions of most species at SDZ were consistent with those obtained at the Mace Head station in Ireland. The background conditions were distinguished from pollution events, and the enhanced mole fractions were used to estimate the emissions of four categories of fluorinated gases (F-gases) from northern China using a tracer ratio method. The CO2-equivalent (CO2-equiv) emission of F-gases from northern China reached 181 ± 18 Tg year-1 during 2020-2021. Among the four categories of F-gases estimated, SF6 accounted for the highest proportion of CO2-equiv emissions (24%), followed by HFC-23 (22%), HFC-125 (17%), HFC-134a (13%), NF3 (10%), CF4 (5.9%), HFC-143a (3.9%), HFC-32 (3.4%), and HFC-152a (0.2%).

Pathway and Cost-Benefit Analysis to Achieve China's Zero Hydrofluorocarbon Emissions.

Global hydrofluorocarbon (HFC) cumulative emissions will be more than 20 Gt CO2-equiv during 2020-2060 and have a non-negligible impact on global warming even in full compliance with the Kigali Amendment (KA). Fluorochemical manufacturers (including multinationals) in China have accounted for about 70% of global HFC production since 2015, of which about 60% is emitted outside China. This study built an integrated model (i.e., DECAF) to estimate both territorial and exported emissions of China under three scenarios and assess the corresponding climate effects as well as abatement costs. Achieving near-zero territorial emissions by 2060 could avoid 23 ± 4 Gt CO2-equiv of cumulative territorial emissions (compared to the 2019 Baseline scenario) during 2020-2060 at an average abatement cost of 9 ± 6 USD/t CO2-equiv. Under the near-zero emission (including territorial and abroad) pathway, radiative forcing from HFCs will peak in 2037 (60 ± 6 mW/m2) with a 33% peak reduction and 8 years in advance compared to the path regulated by the KA, and the radiative forcing by 2060 will be lower than that in 2019. Accelerated phase-out of HFC production in China could provide a possibility for rapid global HFC abatement and achieve greater climate benefits.

Banks, emissions, and environmental impacts of China's ozone depletion substances and hydrofluorocarbon substitutes during 1980-2020.

Ozone-depleting substances (ODSs), which also contribute to global warming, have been controlled by the Montreal Protocol (MP) since 1987. China joined the MP in 1991 and began reducing production and consumption of ODSs in the country, leading to a decrease in emissions of ODSs. Based on the Intergovernmental Panel on Climate Change guidelines, the latest emission factors and actual consumption in China (MP scenario), both the historical banks and the historical emissions of ODSs and substitute hydrofluorocarbons (HFCs) during 1980-2020 were calculated. To understand the reduction in ODS and HFC emissions by implementing the MP, we also estimated China's virtual emissions (NMP, i.e., the amount of ODS emissions without the MP) over the same period. The avoided cumulative ODS consumption and emission values of 10.8 and 5.8 (4.8-6.9) million tonnes (Mt) of CFC-11-equivalent (eq), respectively, were estimated by comparing the two scenarios. Furthermore, 26 (22-33) giga tonnes (Gt) of CO2-eq emissions, equivalent to an increase of 0.031 W m-2 radiative forcing, were estimated to be avoided by 2020, which will prevent an additional 0.025 °C increase in temperature. The MP implemented by China has resulted in substantial environmental benefits over the last 30 years. However, owing to the massive use of HFCs as substitutes, the cumulative emissions reached 2286 Mt. CO2-eq during 1990-2020, and it will be challenging to phase down HFCs in the environment after China ratified the Kigali Amendment in 2021.

In-silico target prediction by ensemble chemogenomic model based on multi-scale information of chemical structures and protein sequences.

Identification and validation of bioactive small-molecule targets is a significant challenge in drug discovery. In recent years, various in-silico approaches have been proposed to expedite time- and resource-consuming experiments for target detection. Herein, we developed several chemogenomic models for target prediction based on multi-scale information of chemical structures and protein sequences. By combining the information of a compound with multiple protein targets together and putting these compound-target pairs into a well-established model, the scores to indicate whether there are interactions between compounds and targets can be derived, and thus a target prediction task can be completed by sorting the outputted scores. To improve the prediction performance, we constructed several chemogenomic models using multi-scale information of chemical structures and protein sequences, and the ensemble model with the best performance was used as our final model. The model was validated by various strategies and external datasets and the promising target prediction capability of the model, i.e., the fraction of known targets identified in the top-k (1 to 10) list of the potential target candidates suggested by the model, was confirmed. Compared with multiple state-of-art target prediction methods, our model showed equivalent or better predictive ability in terms of the top-k predictions. It is expected that our method can be utilized as a powerful computational tool to narrow down the potential targets for experimental testing.