Search

Abstract Prostate cancer (PCa), with high heterogeneity and poor prognosis, is one of the most common malignant tumors in men. Circular RNAs (circRNAs) have been identified in tumor progression and resistance to medication in numerous studies. However, the role of circ_0001047 in PCa is unclear. In this research, we found that circ_0001047 had low expression in PCa cells and tissues and was negatively correlated with testosterone secretion in vivo. Overexpression of circ_0001047 inhibited the proliferation, migration, invasion, and anti-apoptotic abilities of human PCa cells in vitro. Mechanistically, circ_0001047 promoted the expression of FKBP5 through sponge adsorption of miR-122-5p and then inhibited the proliferation, anti-apoptotic migration, and invasion abilities of PCa cells. In addition, overexpression of circ_0001047 enhanced the sensitivity of PCa cells to abiraterone by inhibiting AKT phosphorylation activation through upregulation of FKBP5/PHLPP1. This study revealed a novel mechanism by which circ_0001047 regulates PCa progression and treatment sensitivity via the miR-122-5p/FKBP5/PHLPP1/AKT axis. These findings deepen our comprehension of the molecular mechanisms in latent PCa progression and treatment resistance. Graphical Abstract

Utilizing standardized artificial regulatory sequences to fine-tuning the expression of multiple metabolic pathways/genes is a key strategy in the creation of efficient microbial cell factories. However, when regulatory sequence expression strengths are characterized using only a few reporter genes, they may not be applicable across diverse genes. This introduces great uncertainty into the precise regulation of multiple genes at multiple expression levels. To address this, our study adopted a fluorescent protein fusion strategy for a more accurate assessment of target protein expression levels. We combined 41 commonly-used metabolic genes with 15 regulatory sequences, yielding an expression dataset encompassing 520 unique combinations. This dataset highlighted substantial variation in protein expression level under identical regulatory sequences, with relative expression levels ranging from 2.8 to 176-fold. It also demonstrated that improving the strength of regulatory sequences does not necessarily lead to significant improvements in the expression levels of target proteins. Utilizing this dataset, we have developed various machine learning models and discovered that the integration of promoter regions, ribosome binding sites, and coding sequences significantly improves the accuracy of predicting protein expression levels, with a Spearman correlation coefficient of 0.72, where the promoter sequence exerts a predominant influence. Our study aims not only to provide a detailed guide for fine-tuning gene expression in the metabolic engineering of Escherichia coli but also to deepen our understanding of the compatibility issues between regulatory sequences and target genes.

Abstract Traditional light‐driven metal‐organic‐frameworks (MOFs)‐based micromotors (MOFtors) are typically constrained to two‐dimensional (2D) motion under ultraviolet or near‐infrared light and often demonstrate instability and susceptibility to ions in high‐saline environments. This limitation is particularly relevant to employing micromotors in water purification, as real wastewater is frequently coupled with high salinity. In response to these challenges, ultrastable MOFtors capable of three‐dimensional (3D) motion under a broad spectrum of light through thermophoresis and electrophoresis are successfully synthesized. The MOFtors integrated photocatalytic porphyrin MOFs (PCN‐224) with a photothermal component made of polypyrrole (PPy) by three distinct methodologies, resulting in micromotors with different motion behavior and catalytic performance. Impressively, the optimized MOFtors display exceptional maximum velocity of 1305 ± 327 µm s−1 under blue light and 2357 ± 453 µm s−1 under UV light. In harsh saline environments, these MOFtors are not only maintain high motility but also exhibit superior tetracycline hydrochloride (TCH) removal efficiency of 3578 ± 510 mg g−1, coupling with sulfate radical‐based advanced oxidation processes and peroxymonosulfate. This research underscores the significant potential of highly efficient MOFtors with robust photocatalytic activity in effectively removing TCH in challenging saline conditions, representing a substantial advancement in applying MOFtors within real‐world water treatment technologies.

BackgroundMultiple intersections, including socioeconomic inequalities, influence health equity for disabled people and sub-populations. However, this association has not been sufficiently analyzed among Chinese-impaired persons. This study aimed to investigate the health services utilization and inequalities in middle and older adult persons with disabilities and subgroups.MethodsThe China Health and Retirement Longitudinal Study (CHARLS) database in 2011, 2013, 2015, and 2018 were used. Health services utilization was measured by outpatient, inpatient, and self-treatment service utilization. Types of disabilities were classified into six categories. The pooled cross-section regression, concentration index, horizontal inequity index, and concentration index decomposition were used to evaluate inequalities and explore their main contributing factor.ResultsThe utilization and non-utilization of healthcare services showed variations across years (p

Transarterial chemoembolization (TACE) is an established therapeutic strategy for intermediate stage Barcelona Clinic Liver Cancer (BCLC) hepatocellular carcinoma (HCC). However, patients who are early refractory to TACE may not benefit from repeated TACE treatment. Our primary objective was to assess the diagnostic value of inflammatory markers in identifying early TACE refractory for patients with early (BCLC 0 and A) or intermediate (BCLC B) stage HCC. We retrospectively reviewed the HCC patients who underwent TACE as the initial treatment in two hospitals. Patients with early TACE refractoriness had significantly poorer median overall survival (OS) (16 vs 40 months, P

Abstract Various mechanical effects have been reported with molecular materials, yet organic crystals capable of multiple dynamic effects are rare, and at present, their performance is worse than some of the common actuators. Here, we report a confluence of different mechanical effects across three polymorphs of an organic crystal that can efficiently convert light into work. Upon photodimerization, acicular crystals of polymorph I display output work densities of about 0.06–3.94 kJ m−3, comparable to ceramic piezoelectric actuators. Prismatic crystals of the same form exhibit very high work densities of about 1.5–28.5 kJ m−3, values that are comparable to thermal actuators. Moreover, while crystals of polymorph II roll under the same conditions, crystals of polymorph III are not photochemically reactive; however, they are mechanically flexible. The results demonstrate that multiple and possibly combined mechanical effects can be anticipated even for a simple organic crystal.

Abstract Background Patients with hepatocellular carcinoma (HCC) who undergo transarterial chemoembolization (TACE) may have varied outcomes based on their liver function and tumor burden diversity. This study aims to assess the prognostic significance of the tumor burden score (TBS) in these patients and develop a prognostic model for their overall survival. Methods The study involved a retrospective analysis of 644 newly diagnosed HCC patients undergoing TACE treatment. The individuals were assigned randomly to a training cohort (n = 452) and a validation cohort (n = 192). We utilized a multivariate Cox proportional risk model to identify independent preoperative predictive factors. We then evaluated model performance using the area under the curve (AUC), consistency index (c-index), calibration curve, and decision curve analysis (DCA) methods. Results The multivariate analysis revealed four prognostic factors associated with overall survival: Tumor Burden Score, Tumor Extent, Types of portal vein invasion (PVI), and Child-Pugh score. The total score was calculated based on these factors. The model demonstrated strong discriminative ability with high AUC values and c-index, providing high net clinical benefits for patients. Based on the model’s scoring results, patients were categorized into high, medium, and low-risk groups. These results were validated in the validation cohort. Conclusions The tumor burden score shows promise as a viable alternative prognostic indicator for assessing tumor burden in cases of HCC. The new prognostic model can place patients in one of three groups, which will estimate their individual outcomes. For high-risk patients, it is suggested to consider alternative treatment options or provide the best supportive care, as they may not benefit significantly from TACE treatment.

BackgroundHybrid immunity (a combination of natural and vaccine-induced immunity) provides additional immune protection against the coronavirus disease 2019 (COVID-19) reinfection. Today, people are commonly infected and vaccinated; hence, hybrid immunity is the norm. However, the mitigation of the risk of Omicron variant reinfection by hybrid immunity and the durability of its protection remain uncertain. This meta-analysis aims to explore hybrid immunity to mitigate the risk of Omicron variant reinfection and its protective durability to provide a new evidence-based basis for the development and optimization of immunization strategies and improve the public’s awareness and participation in COVID-19 vaccination, especially in vulnerable and at-risk populations.MethodsEmbase, PubMed, Web of Science, Chinese National Knowledge Infrastructure, and Wanfang databases were searched for publicly available literature up to 10 June 2024. Two researchers independently completed the data extraction and risk of bias assessment and cross-checked each other. The Newcastle-Ottawa Scale assessed the risk of bias in included cohort and case–control studies, while criteria recommended by the Agency for Health Care Research and Quality (AHRQ) evaluated cross-sectional studies. The extracted data were synthesized in an Excel spreadsheet according to the predefined items to be collected. The outcome was Omicron variant reinfection, reported as an Odds Ratio (OR) with its 95% confidence interval (CI) and Protective Effectiveness (PE) with 95% CI. The data were pooled using a random- or fixed-effects model based on the I2 test. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.ResultsThirty-three articles were included. Compared with the natural immunity group, the hybrid immunity (booster vaccination) group had the highest level of mitigation in the risk of reinfection (OR = 0.43, 95% CI:0.34–0.56), followed by the complete vaccination group (OR = 0.58, 95% CI:0.45–0.74), and lastly the incomplete vaccination group (OR = 0.64, 95% CI:0.44–0.93). Compared with the complete vaccination-only group, the hybrid immunity (complete vaccination) group mitigated the risk of reinfection by 65% (OR = 0.35, 95% CI:0.27–0.46), and the hybrid immunity (booster vaccination) group mitigated the risk of reinfection by an additional 29% (OR = 0.71, 95% CI:0.61–0.84) compared with the hybrid immunity (complete vaccination) group. The effectiveness of hybrid immunity (incomplete vaccination) in mitigating the risk of reinfection was 37.88% (95% CI, 28.88–46.89%) within 270–364 days, and decreased to 33.23%% (95% CI, 23.80–42.66%) within 365–639 days; whereas, the effectiveness after complete vaccination was 54.36% (95% CI, 50.82–57.90%) within 270–364 days, and the effectiveness of booster vaccination was 73.49% (95% CI, 68.95–78.04%) within 90–119 days.ConclusionHybrid immunity was significantly more protective than natural or vaccination-induced immunity, and booster doses were associated with enhanced protection against Omicron. Although its protective effects waned over time, vaccination remains a crucial measure for controlling COVID-19.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier, CRD42024539682.

In this study, phosphoric acid activation was employed to synthesize nitrogen-doped mesoporous activated carbon (designated as MR1) from Lentinus edodes (shiitake mushroom) residue, while aiming to efficiently remove acetaminophen (APAP), carbamazepine (CBZ), and metronidazole (MNZ) from aqueous solutions. We characterized the physicochemical properties of the produced adsorbents using scanning electron microscopy (SEM), nitrogen adsorption isotherms, and X-ray photoelectron spectroscopy (XPS). MR1, MR2, and MR3 were prepared using phosphoric acid impregnation ratios of 1, 2, and 3 mL/g, respectively. Notably, MR1 exhibited a significant mesoporous structure with a volume of 0.825 cm3/g and a quaternary nitrogen content of 2.6%. This endowed MR1 with a high adsorption capacity for APAP, CBZ, and MNZ, positioning it as a promising candidate for water purification applications. The adsorption behavior of the contaminants followed the Freundlich isotherm model, suggesting a multilayer adsorption process. Notably, MR1 showed excellent durability and recyclability, maintaining 95% of its initial adsorption efficiency after five regeneration cycles and indicating its potential for sustainable use in water treatment processes.

Abstract Neutrophil extracellular traps (NETs) seriously impede diabetic wound healing. The disruption or scavenging of NETs using deoxyribonuclease (DNase) or cationic nanoparticles has been limited by liberating trapped bacteria, short half‐life, or potential cytotoxicity. In this study, a positive correlation between the NETs level in diabetic wound exudation and the severity of wound inflammation in diabetic patients is established. Novel NETs scavenging bio‐based hydrogel microspheres ‘micro‐cage’, termed mPDA‐PEI@GelMA, is engineered by integrating methylacrylyl gelatin (GelMA) hydrogel microspheres with cationic polyethyleneimine (PEI)‐functionalized mesoporous polydopamine (mPDA). This unique ‘micro‐cage’ construct is designed to non‐contact scavenge of NETs between nanoparticles and the diabetic wound surface, minimizing biological toxicity and ensuring high biosafety. NETs are introduced into ‘micro‐cage’ along with wound exudation, and cationic mPDA‐PEI immobilizes them inside the ‘micro‐cage’ through a strong binding affinity to the cfDNA web structure. The findings demonstrate that mPDA‐PEI@GelMA effectively mitigates pro‐inflammatory responses associated with diabetic wounds by scavenging NETs both in vivo and in vitro. This work introduces a novel nanoparticle non‐contact NETs scavenging strategy to enhance diabetic wound healing processes, with potential benefits in clinical applications.

Abstract With the rapid development of white LEDs, the research of new and efficient white light emitting materials has attracted increasing attention. Zero dimensional (0D) organic–inorganic hybrid metal halide perovskites with superior luminescent property are promising candidates for LED application, due to their abundant and tailorable structure. Herein, [(CH3)3S]2SnCl6·H2O is synthesized as a host for dopant ions Bi3+ and Sb3+. The Sb3+ doped, or Bi3+/Sb3+ co-doped, [(CH3)3S]2SnCl6·H2O has a tunable optical emission spectrum by means of varying dopant ratio and excitation wavelength. As a result, we can achieve single-phase materials suitable for emission ranging from cold white light to warm white light. The intrinsic mechanism is examined in this work, to clarify the dopant effect on the optical properties. The high stability of title crystalline material, against water, oxygen and heat, makes it promising for further application. Graphical Abstract

Abstract Background Sanguinarine chloride (S.C) is a benzophenanthrine alkaloid derived from the root of sanguinaria canadensis and other poppy-fumaria species. Studies have reported that S.C exhibits antioxidant, anti-inflammatory, proapoptotic, and growth inhibitory effects, which contribute to its anti-cancer properties. Recent studies suggested that the antitumor effect of S.C through inducing ferroptosis in some cancers. Nevertheless, the precise mechanism underlying the regulation of ferroptosis by S.C remains poorly understood. Methods A small molecule library was constructed based on FDA and CFDA approved small molecular drugs. CCK-8 assay was applied to evaluate the effects of the small molecule compound on tumor cell viability. Prostate cancer cells were treated with S.C and then the cell viability and migration ability were assessed using CCK8, colony formation and wound healing assay. Reactive oxygen species (ROS) and iron accumulation were quantified through flow cytometry analysis. The levels of malondialdehyde (MDA) and total glutathione (GSH) were measured using commercially available kits. RNA-seq analysis was performed to identify differentially expressed genes (DEGs) among the treatment groups. Western blotting and qPCR were utilized to investigate the expression of relevant proteins and genes. In vivo experiments employed a xenograft mice model to evaluate the anti-cancer efficacy of S.C. Results Our study demonstrated that S.C effectively inhibited the viability of various prostate cancer cells. Notably, S.C exhibited the ability to enhance the cytotoxicity of docetaxel in DU145 cells. We found that S.C-induced cell death partially relied on the induction of ferroptosis, which was mediated through up-regulation of HMOX1 protein. Additionally, our investigation revealed that S.C treatment decreased the stability of BACH1 protein, which contributed to HMOX1expression. We further identified that S.C-induced ROS caused BACH1 instability by suppressing USP47expression. Moreover, In DU145 xenograft model, we found S.C significantly inhibited prostate cancer growth, highlighting its potential as a therapeutic strategy. Collectively, these findings provide evidence that S.C could induce regulated cell death (RCD) in prostate cancer cells and effectively inhibit tumor growth via triggering ferroptosis. This study provides evidence that S.C effectively suppresses tumor progression and induces ferroptosis in prostate cancer cells by targeting ROS/USP47/BACH1/HMOX1 axis. Conclusion This study provides evidence that S.C effectively suppresses tumor progression and induces ferroptosis in prostate cancer cells by targeting the ROS/USP47/BACH1/HMOX1 axis. These findings offer novel insights into the underlying mechanism by which S.C inhibits the progression of prostate cancer. Furthermore, leveraging the potential of S.C in targeting ferroptosis may present a new therapeutic opportunity for prostate cancer. This study found that S.C induces ferroptosis by targeting the ROS/USP47/BACH1/HMOX1 axis in prostate cancer cells. Graphical Abstract

BackgroundPreeclampsia (PE) is a pregnancy complication defined by new onset hypertension and proteinuria or other maternal organ damage after 20 weeks of gestation. Although non-invasive prenatal testing (NIPT) has been widely used to detect fetal chromosomal abnormalities during pregnancy, its performance in combination with maternal risk factors to screen for PE has not been extensively validated. Our aim was to develop and validate classifiers that predict early- or late-onset PE using the maternal plasma cell-free DNA (cfDNA) profile and clinical risk factors.MethodsWe retrospectively collected and analyzed NIPT data of 2,727 pregnant women aged 24–45 years from four hospitals in China, which had previously been used to screen for fetal aneuploidy at 12 + 0 ~ 22 + 6 weeks of gestation. According to the diagnostic criteria for PE and the time of diagnosis (34 weeks of gestation), a total of 143 early-, 580 late-onset PE samples and 2,004 healthy controls were included. The wilcoxon rank sum test was used to identify the cfDNA profile for PE prediction. The Fisher’s exact test and Mann–Whitney U-test were used to compare categorical and continuous variables of clinical risk factors between PE samples and healthy controls, respectively. Machine learning methods were performed to develop and validate PE classifiers based on the cfDNA profile and clinical risk factors.ResultsBy using NIPT data to analyze cfDNA coverages in promoter regions, we found the cfDNA profile, which was differential cfDNA coverages in gene promoter regions between PE and healthy controls, could be used to predict early- and late-onset PE. Maternal age, body mass index, parity, past medical histories and method of conception were significantly differential between PE and healthy pregnant women. With a false positive rate of 10%, the classifiers based on the combination of the cfDNA profile and clinical risk factors predicted early- and late-onset PE in four datasets with an average accuracy of 89 and 80% and an average sensitivity of 63 and 48%, respectively.ConclusionIncorporating cfDNA profiles in classifiers might reduce performance variations in PE models based only on clinical risk factors, potentially expanding the application of NIPT in PE screening in the future.

Cirrhosis is an aggressive disease, and over 80 % of liver cancer patients are complicated by cirrhosis, which lacks effective therapies. Transplantation of mesenchymal stem cells (MSCs) is a promising option for treating liver cirrhosis. However, this therapeutic approach is often challenged by the low homing ability and short survival time of transplanted MSCs in vivo. Therefore, a novel and efficient cell delivery system for MSCs is urgently required. This new system can effectively extend the persistence and duration of MSCs in vivo. In this study, we present novel porous microspheres with microfluidic electrospray technology for the encapsulation of bone marrow-derived MSCs (BMSCs) in the treatment of liver cirrhosis. Porous microspheres loaded with BMSCs (Mi-BMSCs) exhibit good biocompatibility and demonstrate better anti-inflammatory properties than BMSCs alone. Mi-BMSCs significantly increase the duration of BMSCs and exert potent anti-inflammatory and anti-fibrosis effects against CCl4 and TAA-induced liver cirrhosis by targeting the TGF-β/Smad signaling pathway to ameliorate cirrhosis, which highlight the potential of Mi-BMSCs as a promising therapeutic approach for early liver cirrhosis.

A quick, easy, cheap, effective, rugged and safe pre-treatment method (QuEChERS) was established to evaluate the risk of tetracycline residues in the muscle of Channa argus. The Box-Behnken design (BBD) response surface optimization method was used to optimize the extraction and purification conditions. The samples were extracted with 10 mL acetonitrile (containing 1% formic acid) and 2 mL 0.1 mol/L Na2EDTA-Mcllvaine buffer solution, and the extracts were purified by 150 mg primary secondary amine（PSA）and 200 mg C18, and detected with Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The result showed that the calibration curve was linear in the range of 0.50~100 ng/mL, with high correlation coefficients (r≥0.999). The limits of detection (LOD) and quantification (LOQ) were 0.25～0.75 μg/kg and 0.84～2.00 μg/kg, respectively. The average recoveries of tetracycline, oxytetracycline, chlortetracycline and doxycycline at three different spiked levels in the muscle of Channa argus were 89.5%～118%, with relative standard deviations (RSDs) of 1.11%～8.88%. This method is simple, sensitive and accurate, and can be used for the rapid quantitative determination of tetracyclines in Channa argus.

Melanoma is the most aggressive and malignant form of skin cancer. Current melanoma treatment methods generally suffer from frequent drug administration as well as difficulty in direct monitoring of drug release. Here, a self-monitoring microneedle (MN)-based drug delivery system, which integrates a dissolving MN patch with aggregation-induced emission (AIE)-active PATC microparticles, is designed to achieve light-controlled pulsatile chemo-photothermal synergistic therapy of melanoma. The PATC polymeric particles, termed D/I@PATC, encapsulate both of chemotherapeutic drug doxorubicin (DOX) and the photothermal agent indocyanine green (ICG). Upon light illumination, PATC gradually dissociates into smaller particles, causing the release of encapsulated DOX and subsequent fluorescence intensity change of PATC particles, thereby not only enabling direct observation of the drug release process under light stimuli, but also facilitating verification of drug release by fluorescence recovery after light trigger. Moreover, encapsulation of ICG in PATC particles displays significant improvement of its photothermal stability both in vitro and in vivo. In a tumor-bearing mouse, the application of one D/I@PATC MN patch combining with two cycles of light irradiation showed excellent controllable chemo-photothermal efficacy and exhibited ∼97% melanoma inhibition rate without inducing any evident systemic toxicity, suggesting a great potential for skin cancer treatment in clinics.

This work investigated the underlying mechanism of thermo-ultrasonic treatment to improve the nutritional properties and emulsion stability of sea bass fish head broth. The effects of ultrasonication on the processing of fish broth were compared with boiling water treatment. The nutritional properties of fish broth mainly include protein, fat, total sugar, 5′-nucleotide and free amino acid content. To achieve a similar effect of nutrient extraction, the thermo-ultrasonic treatment required a shorter time (30 min) than boiling water (120 min). The water-soluble protein, fat and total sugar contents were at their maximum at 120 min of the thermo-ultrasonic treatment. In particular, the fat content increased with the time of thermo-ultrasonic treatment from 0.58% to 2.70%. The emulsion structure of the fish soup was characterized by measuring its color and particle size, using optical microscopy and confocal laser scanning microscopy, and determining its storage stability. Thermo-ultrasonic treatment reduced the particle size of the fish broth emulsion and the fat globules became smaller and more homogeneous. Ultrasonication not only accelerated the nutritional and flavor content of the fish head broth, but also reduced the particle size and enhanced the stability of the emulsified system of the fish broth. The fish head tissue was more severely disrupted by the cavitation effect of an ultrasound, and nutrients migrated more and faster. This was mainly due to the cavitation and mechanical breaking force of the ultrasound on the fish head tissue and the fat globules of the fish broth. Altogether, these findings suggest that the thermo-ultrasonic treatment technique is useful for processing nutrient-rich, storage-stable and ready-to-eat fish head broth.

ObjectiveMore than 90% of the Chinese population have completed 2 doses of inactivated COVID-19 vaccines in Mainland China. However, after China government abandoned strict control measures, many breakthrough infections appeared, and vaccine effectiveness against Omicron BA.2 infection was uncertain. This study aims to investigate the real-world effectiveness of widely used inactivated vaccines during the wave of Omicron variants.MethodsTest-negative case-control study was conducted in this study to analyze the vaccine effectiveness against symptomatic disease caused by the Omicron variant (BA.2) in Fujian, China. Conditional logistic regression was selected to estimate the vaccine effectiveness.ResultsThe study found the vaccine effectiveness against symptomatic COVID-19 is 32.46% (95% CI, 8.08% to 50.37%) at 2 to 8 weeks, and 27.05% (95% CI, 1.23% to 46.12%) at 12 to 24 weeks after receiving booster doses of the inactivated vaccine. Notably, the 3–17 years group had higher vaccine effectiveness after 2 doses than the 18–64 years and over 65 years groups who received booster doses.ConclusionInactivated vaccines alone may not offer sufficient protection for all age groups before the summer of 2022. To enhance protection, other types of vaccines or bivalent vaccines should be considered.

The molecular weight (MW) of an enzyme is a critical parameter in enzyme-constrained models (ecModels). It is determined by two factors: the presence of subunits and the abundance of each subunit. Although the number of subunits (NS) can potentially be obtained from UniProt, this information is not readily available for most proteins. In this study, we addressed this gap by extracting and curating subunit information from the UniProt database to establish a robust benchmark dataset. Subsequently, we propose a novel model named DeepSub, which leverages the protein language model and Bi-directional Gated Recurrent Unit (GRU), to predict NS in homo-oligomers solely based on protein sequences. DeepSub demonstrates remarkable accuracy, achieving an accuracy rate as high as 0.967, surpassing the performance of QUEEN. To validate the effectiveness of DeepSub, we performed predictions for protein homo-oligomers that have been reported in the literature but are not documented in the UniProt database. Examples include homoserine dehydrogenase from Corynebacterium glutamicum, Matrilin-4 from Mus musculus and Homo sapiens, and the Multimerins protein family from M. musculus and H. sapiens. The predicted results align closely with the reported findings in the literature, underscoring the reliability and utility of DeepSub.

The combined application of steel–FRP composite bars (SFCBs) and seawater sea-sand concrete (SSSC) in marine engineering not only solves the problem of resource scarcity and reduces the construction cost but also avoids the problems of chloride corrosion of steel reinforcement in seawater sea-sand concrete and the lack of ductility of FRP bars. At the same time, the addition of glass fiber (GF) and expansion agent (EA) in appropriate amounts improves the crack resistance and seepage resistance of concrete. However, the durability of SFCB with GF- and EA-reinforced SSSC in freezing–thawing environment remains unclear, which limits its potential application in cryogenic marine engineering. This study investigates the bonding properties between SFCB and GF-EA-SSSC interfaces using eccentric pullout experiments under different thicknesses of concrete protective cover and a number of freezing–thawing cycles. The results showed that the compressive strength and dynamic elastic modulus of SSSC decrease, while the mass loss increases with an increasing number of freezing–thawing cycles. Additionally, the bond strength and stiffness between SFCB and SSSC decrease, leading to an increase in relative slip. However, the rate of bond strength and stiffness loss decreases with an increase in the thickness of the concrete protective cover. Furthermore, formulas for bond strength, relative slip, and bond stiffness are established to quantify the effects of the thickness of the concrete protective cover and the number of freezing–thawing cycles. The experimental values obtained verify the accuracy of these formulas, with a relative error of less than 5%. Moreover, a bond stress–slip constitutive model is developed for SFCB and GF-EA-SSSC, and the fitting results closely resemble the experimental values, demonstrating a high level of model fit.

Cobalt–nitrogen co-doped carbon nanotubes (Co3@NCNT-800) were synthesized via a facile and economical approach to investigate the efficient degradation of organic pollutants in aqueous environments. This material demonstrated high catalytic efficiency in the degradation of carbamazepine (CBZ) in the presence of peroxymonosulfate (PMS). The experimental data revealed that at a neutral pH of 7 and an initial CBZ concentration of 20 mg/L, the application of Co3@NCNT-800 at 0.2 g/L facilitated a degradation rate of 64.7% within 60 min. Mechanistic investigations indicated that the presence of pyridinic nitrogen and cobalt species enhanced the generation of reactive oxygen species. Radical scavenging assays and electron spin resonance spectroscopy confirmed that radical and nonradical pathways contributed to CBZ degradation, with the nonradical mechanism being predominant. This research presents the development of a novel PMS catalyst, synthesized through an efficient and stable method, which provides a cost-effective solution for the remediation of organic contaminants in water.

In this paper, the properties of purple rice powder were improved by mixing high amylose indica rice powder, and the effect of different proportions of mixed powder on the properties of raw materials and the quality of purple rice noodles was studied. The purple rice powder and the indica rice powder were mixed according to a certain proportion to make noodles. The physicochemical properties of mixed powder including amylose content, solubility, swelling power, gel consistency, gelatinization and gel properties were used as determination indexes. And the cooking, anthocyanin content and retention rate and sensory quality of purple rice noodles were used as evaluation indicators. The results showed that the optimum proportion of raw material powder was indica rice powder: purple rice powder=8:2. Under this ratio, the amylose content of the mixed powder increased from 15.75 g/100 g of pure purple rice powder to 26.86 g/100 g, the solubility decreased to 6.24 g/100 g, the swelling force decreased to 6.80 g/g, and the gel consistency decreased from the medium-soft consistency to hard consistency, the trough viscosity, final viscosity and retrogradation value increased, the gel hardness and water holding capacity increased, and the adhesiveness and weight loss rate decreased. The above-mentioned changes in the properties of the raw materials enhanced the structural strength of the purple rice noodles gel, reduced its stickiness, optimized its hydration properties, and finally improved the quality of the purple rice noodles. The quality of purple rice noodles made under the optimum ratio was as follows: The cooking time was 508 s, the broken strip rate was 9.67%, the cooking loss rate was 34.37%, the cooking quality was similar to the commercial rice noodles, the anthocyanin content was 18.36 mg/100 g, the retention rate reached 65.68%, and the color was purple, with the fragrance of purple rice, moderate hardness and softness.

Abstract Background Hydrogels loaded with antimicrobial agents have been widely used for treating infected wound defects. However, hydrogels derived from a porcine dermal extracellular matrix (PADM), containing silver nanoparticles (AgNPs), have not yet been studied. Therefore, we investigated the therapeutic effect of an AgNP-impregnated PADM (AgNP–PADM) hydrogel on the treatment of infected wounds. Methods An AgNP–PADM hydrogel was synthesized by embedding AgNPs into a PADM hydrogel. We examined the porosity, moisture retention, degradation, antibacterial properties, cytotoxicity, antioxidant properties, and ability of the PADM and AgNP–PADM hydrogels to treat infected wounds in animals. Results The PADM and AgNP–PADM hydrogels were pH sensitive, which made them flow dynamically and solidify under acidic and neutral conditions, respectively. The hydrogels also exhibited porous network structures, satisfactory moisture retention, and slow degradation. Additionally, the AgNP–PADM hydrogel showed a slow and sustained release of AgNPs for at least 7 days without the particle size changing. Thus, the AgNPs exhibited adequate antibacterial ability, negligible toxicity, and antioxidant properties in vitro. Moreover, the AgNP–PADM hydrogel promoted angiogenesis and healed infected skin defects in vivo. Conclusions The AgNP–PADM hydrogel is a promising bioderived antibacterial material for clinical application to infected wound dressings.

Objective. To elucidate the mechanism by which LINC00174 promotes colon cancer progression by targeting the microRNA-2467-3p (miR-2467-3p)/enolase 3 (ENO3) axis to regulate inflammation and glycolysis. Methods. The expression of LINC00174 and ENO3 in colon cancer tissues, its relationship with survival rate, and correlation were analyzed using bioinformatic analysis. The effects of LINC00174 overexpression and silencing on the biological behavior of and inflammation in colon cancer cells were analyzed via transfection experiments. The target relationships between miR-2467-3p or LINC00174 and ENO3 were verified using sequence prediction and the dual-luciferase reporter assay, respectively. Furthermore, LINC00174- and/or miR-2467-3p-overexpressing cells were prepared to determine the effects on ENO3 protein levels and glycolysis. Finally, the effects of LINC00174 and/or miR-2467-3p overexpression on colon cancer, ENO3 protein levels, and inflammation were analyzed using a tumor-bearing mice model. Results. LINC00174 and ENO3 were overexpressed and associated with a lower survival rate. LINC00174 was positively correlated with ENO3 in colon cancer tissues. Furthermore, the overexpression of LINC00174 in colon cancer cell lines promoted the proliferation, migration, and invasion of colon cancer cells and inflammation but inhibited apoptosis. The overexpression of miR-2467-3p inhibited ENO3 protein levels, which was attenuated via LINC00174 overexpression. Furthermore, it inhibited the biological behavior of and inflammation and glycolysis in colon cancer cells and blocked their LINC00174-induced promotion. Moreover, using animal experiments, the regulatory effects of LINC00174 on tumor growth, ENO3 protein levels, and inflammation via miR-2467-3p were confirmed. Conclusion. LINC00174 promotes the glycolysis, inflammation, proliferation, migration, and invasion of colon cancer cells and inhibits apoptosis. The cancer-promoting mechanism of LINC00174 is related to targeting miR-2467-3p to promote ENO3 protein levels.

Template design on polymorph control, especially conformational polymorphs, is still in its infancy and the result of polymorph control is often accidental. A method of regulating the crystallization of conformational polymorphs based on the crystal structure similarity of templates and the target crystal form has been developed. Crystal structure similarity was considered to be able to introduce lattice matching (geometric term) with chemical interactions to regulate conformational polymorph nucleation. The method was successfully applied to induce the crystallization of DA7-II [HOOC–(CH2)n−2–COOH (diacids), named DAn, where n = 7, 9, 15, 17 and II represents the metastable polymorph] on the surface of DA15-II. An analogous two-dimensional plane – the (002) face of both DA15-II and DA7-II – was firstly predicted as the epitaxially attached face with similar lattice parameters and the strongest adsorption energy. The powder DA15-II template with the preferred orientation face in (002) presented much stronger inducing DA7-II ability than the template with other preferred orientation faces. The epitaxial growth of DA7-II on DA15-II through an identical (002) face was clearly observed and verified by the single-crystal inducing experiments. The molecular dynamics simulation results demonstrated that the strong interactions occurred between DA7 molecules and the (002) face of DA15-II. This method has been verified and further applied to the crystallization of DA7-II on the surface of DA17-II and DA9-II on the surface of DA15-II. This study developed a strategy based on structure similarity to regulate the conformational polymorph and verified the significant role of lattice matching and chemical effects on the design and preparation of templates.

IntroductionDisabilities may raise heavy medical expenses and rich-poor inequalities. However, data is lacking for the Chinese older populations. This study aimed to measure socioeconomic inequalities in medical expenses amongst the Chinese adult 45 years or older, and explored the main determinants among different disability categories.MethodData from the 2018 China Health and Retirement Longitudinal Study (CHARLS) were used. Disabilities were divided into five categories: physical disabilities, intellectual disability, vision problems, hearing problems, and multiple disabilities. The two-part model was employed to identify the factors that are associated with medical expenditures. Socioeconomic inequalities were measured by the concentration index (CI), and the horizontal inequity index (HI) which adjusts for health needs. Decomposition analysis was further applied to evaluate the contribution of each determinant.ResultsTwo thousand four hundred nineteen people were included in this study. The CIs and HIs of the expenditure were both positive. Amongst the varied types of medical expenses, the highest CIs were found for self-treatment expenses (0.0262). Amongst the five categories of disabilities, the group with vision problem disability reported the highest CIs and HIs for outpatient expenses (CI = 0.0843, HI = 0.0751), self-treatment expenses (CI = 0.0958, HI = 0.1119), and total expenses (CI = 0.0622, HI = 0.0541). The group of intellectual disability reported the highest CI and HI (CI = 0.0707, HI = 0.0625). The decomposition analysis showed that income (80.32%), education (25.14%) and living in the rural areas (13.96%) were the main determinants of medical expenses for HI amongst all types of disabilities.ConclusionFor five types of disabilities, our data shows that medical expenses concentrated in the richer groups in China. Income, education, and rural areas factors were the main contributors to the economic-related inequalities. Health policies to improve the affordability of medical care are needed to decrease inequity of medical expenditures for people with disabilities.

The aim of the present work was to fabricate Schiff base compounds between chitosan and aldehydes and use the resultant aldehyde-chitosan Schiff bases for broccoli preservation. Using an element analyzer, the degree of substitution was calculated as 68.27–94.65%. The aldehyde-chitosan Schiff bases showed acidic sensitivity to rapid hydrolysis for releasing aldehyde at a buffer solution of pH 4–6, in which more than 39% of the aldehydes were released within 10 h. The release of aldehydes endows the aldehyde-chitosan Schiff bases with a better antibacterial activity at pH 5 than at pH 7. In a simulated CO2 (5–15%) atmosphere with high humidity (92%), the hydrolysis of imine bonds (C=N) was triggered and continuously released aldehyde, even without direct contact with the aqueous phase. The application of aldehyde-chitosan Schiff bases significantly extended the shelf life of broccoli from 4 d to 5–7 d and decreased the weight loss of broccoli during storage. In summary, the fabrication of aldehyde-chitosan Schiff bases and the strategy of using pH-response imine bond (C=N) hydrolysis (thus releasing aldehyde to kill microorganisms) were feasible for use in developing EO-incorporated intelligent food packages for vegetable preservation.

Pyrethroids pesticides (PPs) are the widely adopted synthetic pesticides for agriculture and fishery. The frequent use of these pesticides leads to the accumulation of residues in the freshwater environments in China, subsequently affecting aquatic organisms and ecosystems. However, there are few reports on the toxicological and risk assessment of aquaculture aquatic products. In this study, the uptake, depuration kinetics and potential risk to human health and ecology of fenpropathrin, cypermethrin, fenvalerate, and deltamethrin were assessed using tilapia. The results indicated that four PPs were readily accumulated by tilapia. The bioconcentration factors (BCF) of the PPs in plasma and muscle were between 71.3 and 2112.1 L/kg and 23.9–295.3 L/kg, respectively. The half-lives (t1/2) of muscle and plasma were 2.90–9.20 d and 2.57–8.15 d. The risks of PPs residues in the muscle of tilapia and exposed water were evaluated by hazard quotient (HQ) and risk quotient (RQ). Although PPs residues in tilapia had a low dietary risk to human health, the residues in the exposed water had a high ecological risk to fish, daphnia, and green algae. Therefore, assessing the PPs content in freshwater aquaculture and monitoring their dosages and frequencies are highly necessitated to avoid their adverse effect on the aquaculture environment.

In this study, a multi-residue determination method of QuECHERS combined with UHPLC-MS/MS was developed to determine nine β-lactam antibiotics (penicillin G, amoxicillin, ampicillin, cephalexin, cefquinome, ceftiofur, cefazolin, cephapirin, cefuroxime) in aquaculture products. All the nine β-lactam antibiotics exhibited excellent linearity within the range of 2.0–200 ng/mL (cefuroxime: 5.0–200 ng/mL, r greater than 0.999), while the limits of detection (LODs) and quantification (LOQs) were 2.0–5.0 μg/kg and 5.0–10.0 μg/kg, respectively. The recoveries of this method in five aquaculture products (Penaeus Orientalis, Cyprinus Carpio, Channa Argus, Aristichthys Nobilis, and Ctenopharyngodon Idella) ranged from 85.4% to 113.3% and the intra-day and inter-day precisions (%RSDs) were less than 15%. The results suggested the feasibility of this method as a rapid, simple, and accurate approach for determining the residues of the β-lactam antibiotics in aquaculture products.

The complex structure of the blood–brain barrier (BBB), which blocks nearly all large biomolecules, hinders drug delivery to the brain and drug assessment, thus decelerating drug development. Conventional in vitro models of BBB cannot mimic some crucial features of BBB in vivo including a shear stress environment and the interaction between different types of cells. There is a great demand for a new in vitro platform of BBB that can be used for drug delivery studies. Compared with in vivo models, an in vitro platform has the merits of low cost, shorter test period, and simplicity of operation. Microfluidic technology and microfabrication are good tools in rebuilding the BBB in vitro. During the past decade, great efforts have been made to improve BBB penetration for drug delivery using biochemical or physical stimuli. In particular, compared with other drug delivery strategies, sonoporation is more attractive due to its minimized systemic exposure, high efficiency, controllability, and reversible manner. BBB on chips (BOC) holds great promise when combined with sonoporation. More details and mechanisms such as trans-endothelial electrical resistance (TEER) measurements and dynamic opening of tight junctions can be figured out when using sonoporation stimulating BOC, which will be of great benefit for drug development. Herein, we discuss the recent advances in BOC and sonoporation for BBB disruption with this in vitro platform.

In this work, pulsed ultrasound was used to facilitate steady-state reactive crystallization and increase the final yield and productivity of lithium carbonate in continuously operated single and multistage mixed suspension mixed product removal (MSMPR) crystallizers. Experimental analyses of the stirred tank MSMPR cascade were performed to investigate the effects of ultrasound field, residence time and temperature which contributed to the steady-state yield, crystal size distribution and crystal morphology. The results show that pulsed ultrasound can not only significantly enhance the reaction rate, but also help to improve the particle size distribution and the crystal habit. Subsequently, a population balance model was developed and applied to estimate the final yield of the continuous process of the lithium bicarbonate thermal decomposition reaction coupling lithium carbonate crystallization. The consistency of the final yield between the experiments and the simulations proved the reliability of the established model. Through the experimental and simulation analyses, it is demonstrated that the use of pulsed ultrasound, higher final stage temperature, MSMPR cascade design and appropriate residence time help to achieve higher yield and productivity. Furtherly, based on the conclusion drawn, pulsed ultrasound enhanced three-stage MSMPR cascaded lithium carbonate continuous crystallization processes were designed, and the maximum productivity of 44.0 g/h was obtained experimentally.

Handwritten signatures are widely used for identity authorization. However, verifying handwritten signatures is cumbersome in practice due to the dependency on extra drawing tools such as a digitizer, and because the false acceptance of a forged signature can cause damage to property. Therefore, exploring a way to balance the security and user experiment of handwritten signatures is critical. In this paper, we propose a handheld signature verification scheme called SilentSign, which leverages acoustic sensors (i.e., microphone and speaker) in mobile devices. Compared to the previous online signature verification system, it provides handy and safe paper-based signature verification services. The prime notion is to utilize the acoustic signals that are bounced back via a pen tip to depict a user’s signing pattern. We designed the signal modulation stratagem carefully to guarantee high performance, developed a distance measurement algorithm based on phase shift, and trained a verification model. In comparison with the traditional signature verification scheme, SilentSign allows users to sign more conveniently as well as invisibly. To evaluate SilentSign in various settings, we conducted comprehensive experiments with 35 participants. Our results reveal that SilentSign can attain 98.2% AUC and 1.25% EER. We note that a shorter conference version of this paper was presented in Percom (2019). Our initial conference paper did not finish the complete experiment. This manuscript has been revised and provided additional experiments to the conference proceedings; for example, by including System Robustness, Computational Overhead, etc.

Pectin is a potential polysaccharide-based emulsifier, but the stabilized emulsions suffer from insufficient emulsion stability. Therefore, modification is needed to enhance its emulsification performance to cater to practical applications. The genipin-crosslinking strategy was used in this work to modify pectin with different sources and extraction conditions. Chemical composition analysis, molecular weight (Mw), and radius of gyration (Rg) measurement revealed that sugar beet pectin (SBP) has a more compact and flexible conformation than commercial citrus pectin (CP) and apple pectin (AP), indicated by the significantly (p < 0.05) larger Mw/Rg of SBP (18.1–11.3 kg/mol/nm) than CP (8.3 kg/mol/nm) and AP (8.0 kg/mol/nm). Crosslinking modification significantly increased the Mw, radius of gyration, and viscosity. This significantly (p < 0.05) improved the emulsifying stability (a smaller increase in droplets size) by the contribution of both thicker adsorbed hydrated layers at the oil-water interface with a stronger steric-hindrance effect and larger viscosity effect to slow down droplet collision. The formation of a blue-black substance from crosslinking reaction was able to block the UV radiation, which significantly improved the photostability of β-carotene-loaded emulsions. Altogether, genipin-crosslinking is feasible to modify pectin of different sources to enhance the emulsion stability and for use as a vehicle for delivering bioactive compounds.

Packet processing offloads are increasingly needed by high-speed networks. This paper proposes a high throughput, low latency, scalable and reconfigurable Match-Action Table (MAT) architecture based on the open source FPGA-based NIC Corundum. The flexibility and capability of this scheme is demonstrated by an example implementation of IP layer forwarding offload. It makes the NIC work as a router that can forward packets for different subnet and virtual local area networks (VLAN). Experiments are performed on a Zynq MPSoC device with two QSFPs and the results show that it can work at line rate of 8 × 25 Gbps (200 Gbps), within a maximum latency of 76 nanoseconds. In addition, a high-performance MAT pipeline with full-featured, resource-efficient TCAM and a compact frame merging deparser are presented.

In order to eliminate the noise in the pumping system and prolong the service life of the equipment, an optimization design method for a muffler structure is proposed. The inside of the muffler is designed with a water guide cone which plays the role of diverting the fluid in the pipeline. The muffler shell, the wall surface of the water guide cone, and the circular bottom plate adopt a porous structure. In order to achieve the best sound suppression effect of the muffler structure, the effects of different channel expansion angles and the flow area on the performance of muffler are studied the results show that when the flow channel expansion angle of the muffler is 145° and the flow area ratio is 3 times, the noise elimination performance of the muffler is the best. The structural optimization of the muffler studied in this paper is of great significance to noise reduction in the pumping system.

CNN extracts the signal characteristics layer by layer through the local perception of convolution kernel, but the rotation speed and sampling frequency of the vibration signal of rotating equipment are not the same. Extracting different signal features with a fixed convolution kernel will affect the local feature perception and ultimately affect the learning effect and recognition accuracy. In order to solve this problem, the matching between the size of convolution kernel and the signal (rotation speed, sampling frequency) was optimized with the matching relation obtained. Through the study of this paper, the ability of extracting vibration features of CNN was improved, and the accuracy of vibration state recognition was finally improved to 98%.

Global climate change and urban heat island intensification are making many cities dangerously hot during heat waves. There is a need for a clear process for applying microclimate information in urban design to create cooler cities. A recent paper points out the gaps in research methodology and suggests the need for implementation-oriented research. It suggests action steps to take research from theory to practice. The framework has five steps, and in our paper, we have addressed four of those steps: (1) understanding the needs of designers; (2) integrated research on urban microclimate factors; (3) development of guidance methods for better design; and (4) developing user-friendly tools. To address the first step, a group of Chinese landscape architects was given a questionnaire and it was found that they perceived principles and guidelines as being the most useful microclimatic design methods. The second step was addressed through a case study with on-site measurements and modeling. In step 3, microclimate information was used to redesign the site. The process that followed addressed the fourth step by illustrating user-friendly tools.

Traditional methods of analyzing genes mainly focus on a single gene. However, they are time consuming, costly, and neglect the interaction between genes. To overcome the shortcomings of traditional methods, many computational techniques have been proposed for gene analysis. Computational methods posit that the interaction between genes forms a network. By analyzing the topological characteristics of the network, a type of node, “hubs,”is identified. Only a small fraction of nodes is called “hubs,”but they interact with many partners in the network. Several methods are used to find “hubs”in a network. However, they are not comprehensive. Nevertheless, searching for more information about genes in a network remains challenging. In this paper, we integrate HumanNet and a framework to find a structural hole (SH) spanner. We classify genes into three classes (SH, normal, and non-SH). We also classify genes into three classes according to degree and betweenness. Enrichment analysis reveals that the SH genes are enriched for an essential one. Furthermore, enrichment analyses of disease mutations, viruses, and drugs consistently show that the SH genes are preferred targets and are important in cellular state transition. Functional enrichment shows that the biological function that the SH genes over represent is related to cell function. We demonstrate that by finding the structural hole spanner in HumanNet, we can find the SH genes that are essential and indispensable in cellular life. In addition, we identify the SH genes that are key players in cellular state transition.

Rich in Fe, Ce, Mn, Si and other elements which have good catalytic activity, Bayan Obo rare-earth tailings are naturally advantaged as the carrier of denitrification catalysts. In this paper, pseudo boehmite (γ-Al2O3) was mixed with Bayan Obo tailings using different ball milling methods for modification to prepare NH3-SCR catalysts. The effect of different mixing methods on the SCR denitrification activity at a low temperature was investigated and the prepared catalysts were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), temperature programed desorption (NH3-TPD), temperature programed reduction (H2-TPR) and other means. The conversion rate of NOx at 250–350 °C was above 80% and the highest conversion rate of NOx of 90% was achieved at 300 °C. SEM and XRD revealed that the tailings modified by pseudo boehmite (γ-Al2O3) using the ordinary ball milling method have loose structure and good dispersion of active substances, and specific surface area (BET) analysis shows that the tailings have the maximum specific surface area and pore volume. However, over grinding and secondary spheronization were observed in the tailings modified by pseudo boehmite (γ-Al2O3) using high energy ball milling method, leading to the decrease of specific surface area and pore volume, poor dispersion of active substances, and ultimately low denitrification rate.

Global climate change and urban heat island intensification are making many cities dangerously hot during heat waves and uncomfortably hot much of the time. Research has identified ways that urban environments can be designed to reduce the heat, but much of the information is too technical or has not been interpreted or communicated so as to be available to landscape architects. This study identifies ways that landscape architecture researchers have applied microclimate information in design to proactively create more thermally comfortable outdoor environments. A systematic review that assessed the growing recognition of microclimatic factors in design revealed four main approaches: principles and guidelines, strategies, mapping, and evaluation. The advantages and limitations of each have been noted, and a diagram has been developed that matches each approach with specific steps in the landscape architectural design process. The study also identified four areas where microclimate has potential for use in landscape architecture but that are currently not being very actively studied: education, modeling and visualization, policy, and ideation. Microclimatic design has the potential to enhance the health and well-being of the public through the design of thermally comfortable outdoor environments.

Identifying drug-target interactions will greatly narrow down the scope of search of candidate medications, and thus can serve as the vital first step in drug discovery. Considering that in vitro experiments are extremely costly and time-consuming, high efficiency computational prediction methods could serve as promising strategies for drug-target interaction (DTI) prediction. In this review, our goal is to focus on machine learning approaches and provide a comprehensive overview. First, we summarize a brief list of databases frequently used in drug discovery. Next, we adopt a hierarchical classification scheme and introduce several representative methods of each category, especially the recent state-of-the-art methods. In addition, we compare the advantages and limitations of methods in each category. Lastly, we discuss the remaining challenges and future outlook of machine learning in DTI prediction. This article may provide a reference and tutorial insights on machine learning-based DTI prediction for future researchers.