Research Progresses and Applications of Knowledge Graph Embedding Technique in Chemistry.

A knowledge graph (KG) is a technique for modeling entities and their interrelations. Knowledge graph embedding (KGE) translates these entities and relationships into a continuous vector space to facilitate dense and efficient representations. In the domain of chemistry, applying KG and KGE techniques integrates heterogeneous chemical information into a coherent and user-friendly framework, enhances the representation of chemical data features, and is beneficial for downstream tasks, such as chemical property prediction. This paper begins with a comprehensive review of classical and contemporary KGE methodologies, including distance-based models, semantic matching models, and neural network-based approaches. We then catalogue the primary databases employed in chemistry and biochemistry that furnish the KGs with essential chemical data. Subsequently, we explore the latest applications of KG and KGE in chemistry, focusing on risk assessment, property prediction, and drug discovery. Finally, we discuss the current challenges to KG and KGE techniques and provide a perspective on their potential future developments.

Correlation and Clinical Significance of HBD-2 and CXCL-1/2 Levels at Skin Lesions with Psoriasis Vulgaris Severity.

OBJECTIVE: This study was performed to explore the clinical significance of the expression of human beta-defensin 2 (HBD-2) and chemokine ligand 1/2 (CXCL-1/2) in psoriasis vulgaris. METHODS: This study retrospectively included the study group (n = 160) and control group (n = 100) for analysis. The levels of inflammatory indicators, blood biochemical indicators, and immune indicators using ELISA. The psoriasis area and severity index (PASI) was used to evaluate disease severity. Levels of HBD-2, CXCL-1, CXCL-2 and CCL20 were determined by RT-PCR. The correlations of HBD-2, CXCL-1 and CXCL-2 levels with CCL20 and PASI scores were analyzed. The diagnostic value of HBD-2, CXCL-1 and CXCL-2 in psoriasis vulgaris was analyzed by ROC curve. RESULTS: HBD-2, CXCL-1 and CXCL-2 were highly expressed in the lesions of psoriasis vulgaris patients, and were positively correlated with CCL20 and PASI score. HBD-2, CXCL-1 and CXCL-2 alone or in combination had high diagnostic value for psoriasis vulgaris and severe psoriasis, and the combined diagnostic value of the three was higher than that of a single indicator. CONCLUSION: HBD-2, CXCL-1, and CXCL-2 levels are closely related to the severity of psoriasis vulgaris and can effectively diagnose the occurrence and progression of psoriasis vulgaris.

Breather wave solutions on the Weierstrass elliptic periodic background for the (2 + 1)-dimensional generalized variable-coefficient KdV equation.

In this paper, the Nth Darboux transformations for the (2+1)-dimensional generalized variable-coefficient Koretweg-de Vries (gvcKdV) equation are proposed. By using the Lamé function method, the generalized Lamé-type solutions for the linear spectral problem associated with the gvcKdV equation with the static and traveling Weierstrass elliptic ℘-function potentials are derived, respectively. Then, the nonlinear wave solutions for the gvcKdV equation on the static and traveling Weierstrass elliptic ℘-function periodic backgrounds under some constraint conditions are obtained, respectively, whose evolutions and dynamical properties are also discussed. The results show that the degenerate solutions on the periodic background can be obtained by taking the limits of the half-periods ω1,ω2 of ℘(x), and the evolution curves of nonlinear wave solutions on the periodic background are determined by the coefficients of the gvcKdV equations.

Symmetry-Broken 2D Lead-Tin Mixed Chiral Perovskite for High Asymmetry Factor Circularly Polarized Light Detection.

Symmetry-broken-induced spin splitting plays a key role for selective circularly polarized light absorption and spin carrier transport. Asymmetrical chiral perovskite is rising as the most promising material for direct semiconductor-based circularly polarized light detection. However, the increase of asymmetry factor and extension of response region remain to be a challenge. Herein, we fabricated a two-dimensional tin-lead mixed chiral perovskite with tunable absorption in the visible region. Theoretical simulation indicates that the mixing of the tin and lead in chiral perovskite breaks the symmetry of the pure ones, resulting in pure spin splitting. We then fabricated a chiral circularly polarized light detector based on this tin-lead mixed perovskite. A high asymmetry factor for the photocurrent of 0.44 is achieved, which is 144% higher than pure lead 2D perovskite, and it is the highest value reported for the pure chiral 2D perovskite-based circularly polarized light detector using a simple device structure.

A cross-sectional survey on the lung ultrasound training and practice of respiratory therapists in mainland China.

PURPOSE: This national study aimed to investigate the lung ultrasound (LUS) training and practice of respiratory therapists (RTs) in mainland China. METHODS: A cross-sectional multicenter survey was conducted from May 22, 2021 to August 12, 2021, through online platforms. This survey included RTs in mainland China. The survey was divided into four sections: (1) demographic characteristics and basic information; (2) basic information about LUS training and practice; (3) LUS practice details; and (4) Other ultrasound training and practice. RESULTS: A total of 514 responses were received, and 494 valid responses were included in the analysis. 81.2% (401/494) participants' highest degree of education was a bachelor's degree, and 43.1% (213/494) participants were at level II in terms of job ranking. 99.2%(490/494) participants agreed that the RTs needed to learn lung ultrasound, but only 12.3% (61/494) participants had received a LUS training course. Further, 66.2% (327/494) experienced participants responded to Sect. 3. Most of RTs used LUS when the patient had hypoxia (265/327, 81%) or dyspnea (260/317, 79.5%); they also used it during spontaneous breathing trial(SBT) (191/327, 58.4%) or in prone position (177/327, 54.1%). The A-line (302/327, 92.4%), B-line (299/327, 91.4%), lung slide (263/327, 80.4%), and bat sign (259/327, 79.2%) were well known as LUS signs. Also, 30.6% (100/327) participants did not use the LUS protocol in their clinical practice, and only 25.4%(83/327) participants said they had used LUS scores. Moreover, 55.7% (182/327) participants frequently changed the respiratory therapy strategy according to LUS results. CONCLUSIONS: We should improve the number and workplace of RTs in mainland China in the future. We should also standardize the application of LUS practice and training for RTs in mainland China and establish corresponding certification pathways.

lncRNA ZNF649-AS1 Induces Trastuzumab Resistance by Promoting ATG5 Expression and Autophagy.

The regulatory mechanism of long non-coding RNAs (lncRNAs) in trastuzumab resistance is not well established to date. In this research, we identified differentially expressed lncRNA and investigated its regulatory role in trastuzumab resistance of breast cancer. HiSeq sequencing and quantitative real-time PCR were performed to identify the dysregulated lncRNAs. Mass spectrometry, RNA fluorescence in situ hybridization (RNA-FISH), and immunoprecipitation assays were performed to identify the direct interactions between ZNF649-AS1 and other associated targets, such as polypyrimidine tract binding protein 1 (PTBP1) and autophagy related 5 (ATG5). Our results showed that ZNF649-AS1 was more highly expressed in trastuzumab-resistant cells compared to sensitive cells. Increased expression of ZNF649-AS1 was associated with a poorer response and shorter survival time of breast cancer patients. ZNF649-AS1 was upregulated by H3K27ac modification at the presence of trastuzumab treatment, and knockdown of ZNF649-AS1 reversed trastuzumab resistance via modulating ATG5 expression and autophagy. Mechanically, ZNF649-AS1 was associated with PTBP1 protein, which further promoted the transcription activity of the ATG5 gene. In conclusion, we demonstrated that H3K27ac modification-induced upregulation of ZNF649-AS1 could cause autophagy and trastuzumab resistance through associating with PTBP1 and promoting ATG5 transcription.

Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation.

BACKGROUND: Although trastuzumab provides significant clinical benefit for HER2-positive breast cancers, responses are limited by the emergence of resistance. Recent evidence suggests that long noncoding RNAs (lncRNAs) play important roles in tumorigenesis and chemoresistance. However, the regulatory mechanism of lncRNAs in trastuzumab resistance is not well established to date. In this research, we identified the differentially expressed lncRNA and investigated its regulatory role in trastuzumab resistance of breast cancer. METHODS: LncRNA microarray and qRT-PCR were performed to identify the dysregulated lncRNAs. Transmission electron microscopy, differential ultracentrifugation and qRT-PCR were used to verify the existence of exosomal AFAP1-AS1 (actin filament associated protein 1 antisense RNA 1). Bioinformatics prediction, RNA fluorescence in situ hybridization (RNA-FISH) and immunoprecipitation assays were performed to identify the direct interactions between AFAP1-AS1 and other associated targets, such as AU-binding factor 1 (AUF1) and ERBB2. Finally, a series gain- or loss-functional assays were done to prove the precise role of AFAP1-AS1 in trastuzumab resistance. RESULTS: AFAP1-AS1 was screened out due to its higher expression in trastuzumab-resistant cells compared to sensitive cells. Increased expression of AFAP1-AS1was associate with poorer response and shorter survival time of breast cancer patients. AFAP1-AS1 was upregulated by H3K27ac modification at promoter region, and knockdown of AFAP1-AS1 reversed trastuzumab resistance. Moreover, extracellular AFAP1-AS1 secreted from trastuzumab resistant cells was packaged into exosomes and then disseminated trastuzumab resistance of receipt cells. Mechanically, AFAP1-AS1 was associated with AUF1 protein, which further promoted the translation of ERBB2 without influencing the mRNA level. CONCLUSION: Exosomal AFAP1-AS1 could induce trastuzumab resistance through associating with AUF1 and promoting ERBB2 translation. Therefore, AFAP1-AS1 level may be useful for prediction of trastuzumab resistance and breast cancer treatment.

Dietary Inflammatory Index Positively Associated With High-Sensitivity C-Reactive Protein Level in Japanese From NIPPON DATA2010.

BACKGROUND: It has been reported that chronic inflammation may play an important role in the pathogenesis of several serious diseases and could be modulated by diet. Recently, the Dietary Inflammatory Index (DII®) was developed to assess the inflammatory potential of the overall diet. The DII has been reported as relevant to various diseases but has not been validated in Japanese. Thus, in the present study, we analyzed the relationship between DII scores and high-sensitivity C-reactive protein (hs-CRP) levels in a Japanese population. METHODS: Data of the National Integrated Project for Prospective Observation of Non-communicable Disease and its Trends in the Aged 2010 (NIPPON DATA2010), which contained 2,898 participants aged 20 years or older from the National Health and Nutrition Survey of Japan (NHNS2010), were analyzed. Nutrient intakes derived from 1-day semi-weighing dietary records were used to calculate DII scores. Energy was adjusted using the residual method. Levels of hs-CRP were evaluated using nephelometric immunoassay. Multiple linear regression analyses were performed. RESULTS: After adjusting for age, sex, smoking status, BMI, and physical activity, a significant association was observed between DII scores and log(CRP+1) (standard regression coefficient = 0.05, P < 0.01). Although it was not statistically significant, the positive association was consistently observed in almost all age-sex subgroups and the non-smoker subgroup. CONCLUSIONS: The current study confirmed that DII score was positively associated with hs-CRP in Japanese.

Molecular and biological characterization of gamma-interferon-inducible lysosomal thiol reductase in silver carp (Hypophthalmichthys molitrix).

Gamma-interferon-inducible lysosomal thiol reductase (GILT) plays an important role in the processing of major histocompatibility complex (MHC) class II-restricted antigens by catalyzing disulfide bonds reduction. Herein, a GILT homolog (ScGILT) was identified from silver carp. Its open reading frame covers 771 base pairs, encoding a protein of 256 amino acids that possesses GILT signature sequence CQHGX2ECX2NX4C, active-site CXXC motif, and two potential N-linked glycosylation sites. The predicted tertiary structures of ScGILT and other GILTs were quite similar in shape and positional arrangement of the key motifs. ScGILT mRNA was constitutively expressed in all detected tissues, with high-level expression in fish immune organs, spleen and head kidney. After stimulation with lipopolysaccharide, the expression of ScGILT mRNA significantly increased in spleen and head kidney cells, and ScGILT protein translocated to late endosomes and lysosomes in HeLa cells. Recombinant ScGILT fused with a His6 tag was expressed and purified, and could reduce the interchain disulfide bonds of IgG at pH 4.5. These results suggested that ScGILT was capable of catalyzing disulfide bonds reduction, and then might play an important role in the processing of MHC class II-restricted antigens in silver carp.

Association between the incidence of varicella and meteorological conditions in Jinan, Eastern China, 2012-2014.

BACKGROUND: Varicella remains an important public health issue in China. In this study we explored the effect of weather conditions on the incidence of varicella in the temperate city of Jinan, Eastern China during 2012-2014 to inform public health prevention and control measures. METHODS: Data on reported cases of varicella were obtained from National Notifiable Disease Report System. Meteorological data for the same time period were obtained from the Jinan Meteorological Bureau. A negative binomial regression model was used to assess the relationships between meteorological variables and the incidence of varicella. Given collinearity between average temperature and atmospheric pressure, separate models were constructed: one including average temperature without atmospheric pressure, the other including atmospheric pressure but without average temperature. Both models included relative humidity, wind velocity, rainfall, sunshine, and year as independent variables. RESULTS: Annual incidence rates of varicella were 44.47, 53.69, and 46.81 per 100,000 for 2012, 2013, and 2014, respectively. Each increase of 100 Pa (hPa) in atmospheric pressure was estimated to be associated with an increase in weekly incidence of 3.35 % (95 % CI = 2.94-3.67 %), while a 1 °C rise in temperature was associated with a decrease of 3.44 % (95 % CI = -3.73-3.15 %) in the weekly incidence of varicella. Similarly, a 1 % rise in relative humidity corresponded to a decrease of 0.50 % or 1.00 %, a 1 h rise in sunshine corresponded to an increase of 1.10 % or 0.50 %, and a 1 mm rise in rainfall corresponded to an increase of 0.20 % or 0.30 %, in the weekly incidence of varicella cases, depending on the variable considered in the model. CONCLUSION: Our findings show that weather factors have a significant influence on the incidence of varicella. Meteorological conditions should be considered as important predictors of varicella incidence in Jinan, Eastern China.

Dynamics of higher-order rational solitons for the nonlocal nonlinear Schrödinger equation with the self-induced parity-time-symmetric potential.

The integrable nonlocal nonlinear Schrödinger equation with the self-induced parity-time-symmetric potential [M. J. Ablowitz and Z. H. Musslimani, Phys. Rev. Lett. 110, 064105 (2013)] is investigated, which is an integrable extension of the standard nonlinear Schrödinger equation. Its novel higher-order rational solitons are found using the nonlocal version of the generalized perturbation (1,N-1)-fold Darboux transformation. These rational solitons illustrate abundant wave structures for the distinct choices of parameters (e.g., the strong and weak interactions of bright and dark rational solitons). Moreover, we also explore the dynamical behaviors of these higher-order rational solitons with some small noises on the basis of numerical simulations.

Rogue waves, rational solitons, and modulational instability in an integrable fifth-order nonlinear Schrödinger equation.

We analytically study rogue-wave (RW) solutions and rational solitons of an integrable fifth-order nonlinear Schrödinger (FONLS) equation with three free parameters. It includes, as particular cases, the usual NLS, Hirota, and Lakshmanan-Porsezian-Daniel equations. We present continuous-wave (CW) solutions and conditions for their modulation instability in the framework of this model. Applying the Darboux transformation to the CW input, novel first- and second-order RW solutions of the FONLS equation are analytically found. In particular, trajectories of motion of peaks and depressions of profiles of the first- and second-order RWs are produced by means of analytical and numerical methods. The solutions also include newly found rational and W-shaped one- and two-soliton modes. The results predict the corresponding dynamical phenomena in extended models of nonlinear fiber optics and other physically relevant integrable systems.

[Short term effect of weather patterns on the incidence of hand foot and mouth disease aged ≤5 years old in Jinan city].

OBJECTIVE: To investigate the effect of weather patterns on the incidence of hand foot and mouth disease (HFMD) in Jinan. METHODS: HFMD confirmed cases aged ≤5 years old for the period of 2012-2014 were collected from National Notifiable Disease Report System (NNDRS). Simultaneous meteorological data, including daily average temperature, relative humidity, atmospheric pressure, wind velocity, rainfall and duration of sunshine were obtained from the website of Jinan meteorological bureau. A negative binomial multivariable regression was used to identify the relationship between meteorological variables and HFMD. RESULTS: During the study period, a total of 40 405 HFMD cases aged ≤5 years old were reported. The incident peak occurred from May to July, a total of 22 254 cases were reported during this period, which accounted for 55.08% of whole cases. After adjusting by "year", each 1 °C rise of weekly average temperature corresponded to an increase of 6.70% (95%CI:6.35% to 7.06%) in the weekly number of HFMD cases, while a 1 kPa rise of weekly average atmospheric pressure corresponded to a decrease in the number of cases by 44.77% (95%CI: -46.23% to -41.91%). Likewise, a one percent rise in weekly average relative humidity corresponded to an increase of 1.96% (95%CI: 1.84% to 2.09%), a 1 m/h rise in weekly average wind velocity corresponded to an increase of 16.63% (95% CI:14.08% to 19.25%), a hour add in weekly duration of sunshine corresponded to a decrease of 0.82% (95% CI : -0.93% to -0.72%), in the weekly number of HFMD cases. CONCLUSION: Weather factors including temperature, atmospheric pressure, relative humidity, wind velocity, and duration of sunshine had a significant influence on occurrence and transmission of HFMD in Jinan city.

Knowledge, attitude, and practice of Chinese parents with infants (aged 0-3 years) toward immunity, gut microbiota and biotics: a comprehensive study.

In the wake of the COVID-19 pandemic, there has been an increasing focus towards infant immunity. The development and maintenance of the immune system are significantly influenced from birth, and is shaped by early-life infant feeding behavior. Hence, the knowledge, attitude, and practice (KAP) of parents play a crucial role in shaping the immune system of infants. A total of 2369 parents across 19 cities in China were surveyed using a self-designed online questionnaire. The KAP questionnaire assessed three domains: immunity, gut microbiota, and biotics (prebiotics, probiotics, and synbiotics). The questionnaire also included questions on infant health. An overwhelming majority of parents (97.90%) placed high value on their children's immunity, and 40.40% of them reported an increased level of concern following the COVID-19 pandemic. Diarrhea (78.80%), colds (75.70%), nighttime crying (73.80%), regurgitation (71.70%) and food retention (66.50%) were the major health issues reported. Knowledge scores toward immunity and gut microbiota were positively correlated to attitude and practice scores, respectively. Attitude scores toward immunity, gut microbiota and biotics were positively correlated to their respective practice scores. Parental knowledge score on immunity was negatively correlated with diarrhea, colds, regurgitation and food retention. On the other hand, parental practice scores toward immunity were negatively correlated with food retention. In regards to gut microbiota, parental knowledge score was negatively correlated with diarrhea, regurgitation and food retention; parental attitude score was negatively correlated with nighttime crying whereas practice score was negatively correlated with diarrhea, regurgitation, food retention and nighttime crying. Attitude score toward biotics was negatively correlated with nighttime crying and practice scores toward biotics was negatively correlated with colds, food retention and nighttime crying. This study demonstrated that significant gaps and misunderstandings exist among parents regarding immunity, gut microbiota health, and biotics. Both public education and interventions are crucial to enhance parental knowledge and practices, thereby improving infant immunity.

METTL1-mediated tRNA m7G methylation and translational dysfunction restricts breast cancer tumorigenesis by fueling cell cycle blockade.

BACKGROUND: RNA modifications of transfer RNAs (tRNAs) are critical for tRNA function. Growing evidence has revealed that tRNA modifications are related to various disease processes, including malignant tumors. However, the biological functions of methyltransferase-like 1 (METTL1)-regulated m7G tRNA modifications in breast cancer (BC) remain largely obscure. METHODS: The biological role of METTL1 in BC progression were examined by cellular loss- and gain-of-function tests and xenograft models both in vitro and in vivo. To investigate the change of m7G tRNA modification and mRNA translation efficiency in BC, m7G-methylated tRNA immunoprecipitation sequencing (m7G tRNA MeRIP-seq), Ribosome profiling sequencing (Ribo-seq), and polysome-associated mRNA sequencing were performed. Rescue assays were conducted to decipher the underlying molecular mechanisms. RESULTS: The tRNA m7G methyltransferase complex components METTL1 and WD repeat domain 4 (WDR4) were down-regulated in BC tissues at both the mRNA and protein levels. Functionally, METTL1 inhibited BC cell proliferation, and cell cycle progression, relying on its enzymatic activity. Mechanistically, METTL1 increased m7G levels of 19 tRNAs to modulate the translation of growth arrest and DNA damage 45 alpha (GADD45A) and retinoblastoma protein 1 (RB1) in a codon-dependent manner associated with m7G. Furthermore, in vivo experiments showed that overexpression of METTL1 enhanced the anti-tumor effectiveness of abemaciclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor. CONCLUSION: Our study uncovered the crucial tumor-suppressive role of METTL1-mediated tRNA m7G modification in BC by promoting the translation of GADD45A and RB1 mRNAs, selectively blocking the G2/M phase of the cell cycle. These findings also provided a promising strategy for improving the therapeutic benefits of CDK4/6 inhibitors in the treatment of BC patients.

Long non-coding RNA LINC01559 serves as a competing endogenous RNA accelerating triple-negative breast cancer progression.

BACKGROUND: Long non-coding RNA (lncRNA) is an endogenous RNA over 200 nt in length involved in gene regulation. LINC01559 is a novel lncRNA that has been identified as a fundamental player in human cancer. However, its role in triple-negative breast cancer (TNBC) remains unknown. Here, we explored the expression, function and clinical implication of LINC01559 in TNBC. METHODS: RNA expression was detected by qRT-PCR analysis. Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), wound healing and Transwell assays were used to test cell viability, DNA synthesis rate, migration and invasion, respectively. The competing endogenous RNA (ceRNA) axis involved in LINC01559 was determined by RNA pull-down and luciferase reporter assays. The xenograft model was used to verify the function of LINC01559 in vivo. RESULTS: LINC01559 was significantly increased in TNBC tissues as compared to matched normal tissues, which was due to high levels of H3K4Me3 and H3K27Ac in the promoter region. Knockdown of LINC01559 inhibited TNBC cell proliferation, migration and invasion in vitro, and also retarded tumor growth and reduced lung metastasis in vivo. Mechanistically, LINC01559 served as a ceRNA that sponged miR-370-3p, miR-485-5p and miR-940, resulting in increasing the expression of a cohort of oncogenes, thus accelerating TNBC progression. CONCLUSIONS: Our data provide a comprehensive analysis of LINC01559 in TNBC, we found that LINC01559 functioned as a carcinogenic ceRNA via sponging miRNAs. Targeting of LINC01559 may be a potential treatment for TNBC patients.

Exosomal long noncoding RNA AGAP2-AS1 regulates trastuzumab resistance via inducing autophagy in breast cancer.

Trastuzumab has been widely used for treatment of HER-2-positive breast cancer patients, however, the clinical response has been restricted due to emergence of resistance. Recent studies indicate that long noncoding RNA AGAP2-AS1 (lncRNA AGAP2-AS1) plays an important role in cancer resistance. However, the precise regulatory function and therapeutic potential of AGAP2-AS1 in trastuzumab resistance is still not defined. In this study, we sought to reveal the essential role of AGAP2-AS1 in trastuzumab resistance. Our results suggest that AGAP2-AS1 disseminates trastuzumab resistance via packaging into exosomes. Exosomal AGAP2-AS1 induces trastuzumab resistance via modulating ATG10 expression and autophagy activity. Mechanically, AGAP2-AS1 is associated with ELAVL1 protein, and the AGAP2-AS1-ELAVL1 complex could directly bind to the promoter region of ATG10, inducing H3K27ac and H3K4me3 enrichment, which finally activates ATG10 transcription. AGAP2-AS1-targeting antisense oligonucleotides (ASO) substantially increased trastuzumab-induced cytotoxicity. Clinically, increased expression of serum exosomal AGAP2-AS1 was associate with poor response to trastuzumab treatment. In conclusion, exosomal AGAP2-AS1 increased trastuzumab resistance via promoting ATG10 expression and inducing autophagy. Therefore, AGAP2-AS1 may serve as predictive biomarker and therapeutic target for HER-2+ breast cancer patients.

Effect of Hydrophobicity on the Anticancer Activity of Fatty-Acyl-Conjugated CM4 in Breast Cancer Cells.

Antimicrobial peptides (AMPs) are important anticancer resources, and exploring AMP conjugates as highly effective and selective anticancer agents would represent new progress in cancer treatment. In this study, we synthesized C4-C16 fatty-acyl-conjugated AMP CM4 and investigated its physiochemical properties and cytotoxicity activity in breast cancer cells. Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and reversed-phase high-performance liquid chromatography (RP-HPLC) showed that long-chain fatty acyl (≥C12) conjugation prevented N-acyl-CM4 from trypsin hydrolysis. RP-HPLC and circular dichroism (CD) spectra showed that the hydrophobicity and helical content of N-acyl-CM4 increased with the acyl length. The acyl chain length was positively related to the cytotoxicity of C8-C16 conjugates, and C12-C16 fatty acyl conjugates exhibited significant cytotoxicity against MX-1, MCF-7, and MDA-MB-231 cells, with IC50 values <8 µM. Flow cytometry and confocal laser scanning microscopy results showed that N-acylated conjugation significantly increased the membrane affinity in breast cancer cells, and C12-C16 acyl conjugates were capable of translocating to the intracellular space, thereby targeting mitochondria and inducing apoptosis. N-acyl-CM4 showed low cytotoxicity against normal mammalian cells and erythrocytes, especially ≤C12 fatty acyl conjugates, exhibiting selective cytotoxicity to breast cancer cells. The current work indicated that increasing hydrophobicity by attaching long fatty acyl (≥C12) to AMPs may be an effective method to improve the anticancer activity, together with selectivity and resistance to trypsin hydrolysis. This finding provides a good strategy to develop AMPs as effective anticancer agents in the future.

Novel education-based intervention to reduce inappropriate antibiotic prescribing for treatment of gonorrhoea in China: protocol for a cluster randomised controlled trial.

INTRODUCTION: Inappropriate use of antibiotics to treat gonorrhoea can lead to antibiotic resistance. Education programmes may be helpful for improving physician prescribing behaviours in accordance with treatment guidelines. As traditional education based on printed materials may have limited effect on guideline-based treatment, innovative education strategies are needed. The current trial aims to assess the effectiveness of a novel education intervention to increase guideline-based treatment of gonorrhoea in China. METHODS AND ANALYSIS: We will conduct a two-arm cluster randomised control trial at 144 hospitals (clusters) in eight Chinese provinces. The intervention will include an online training video developed on the WenJuanXing platform that covers workflows and requirements for managing a patient with uncomplicated gonorrhoea. Outpatient physicians in dermatology (dermatovenerology), urology, andrology and gynaecology will be given access to the video via a quick response code. In hospitals allocated to the control arm, physicians will continue to participate in their standard of care training programme. The primary outcome is the proportion of gonorrhoea antibiotic prescriptions adherent to Chinese national guidelines at the cluster level. In addition, to understand the reasons of physician's non-adherence to the intervention by conducting a questionnaire survey will be considered as the secondary outcome of the study. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Medical Ethics Committee of the Chinese Academy of Medical Sciences Institute of Dermatology (2020-LS-004). All physicians will provide an informed consent prior to participating in the study. Findings of the trial will be disseminated through conferences and peer-reviewed journals, and will be used to develop training programmes for physicians. TRIAL REGISTRATION NUMBER: ChiCTR2000029591.