Epinecidin-1 and lactic acid synergistically inhibit Aeromonas hydrophila through membrane disruption.

Epinecidin-1 (Epi-1) is an antimicrobial peptide originated from fish with various pharmacological activities but carries the risk of acquiring resistance with long-term use. In the present study, we use L-lactic acid to enhance the antibacterial activity of synthesized Epi-1 against the aquaculture and food pathogen Aeromonas hydrophila. The results showed that 5.5 mmol/L lactic acid increased the inhibitory and bactericidal activity of 25 µmol/L Epi-1 against two strains of A. hydrophila. The laser confocal images proved that lactic acid pre-treatment improved the attachment efficiency of Epi-1 in A.hydrophila cells. In addition, lactic acid enhanced the damaging effect of Epi-1 on the cell membrane of A. hydrophila, evidenced by releasing more nucleic acids, proteins, and transmembrane pH ingredients decrease and electromotive force dissipation. SEM images showed that compared with the single Epi-1 treatment, the co-treatment of Epi-1 and lactic acid caused more outer membrane vesicles (OMVs) and more severe cell deformation. These findings proved that lactic acid could enhance the efficiency of Epi-1 against A. hydrophila and shed light on new aspects to avoid resistance of pathogens against Epi-1.

Contributions of Surface Oxidizing Species and Cu+ to the Antibacterial Activities of Cu2O with Different Crystalline Structures.

Although precise regulation of the crystalline structures of metal oxides is an effective method to improve their antibacterial activities, the corresponding mechanisms involved in this process are still unclear. In this study, three kinds of cuprous oxide (Cu2O) samples with different structures of cubes, octahedra, and rhombic dodecahedra (c-Cu2O, o-Cu2O, and r-Cu2O) have been successfully synthesized and their antibacterial activities are compared. The antibacterial activities follow the order of r-Cu2O > o-Cu2O > c-Cu2O, revealing the significant dependence of the antibacterial activities on the crystalline structures of Cu2O. Quenching experiments, as well as the NBT and DPD experiments indicate that ≡CuII─OO• superoxo and ≡CuII─OOH peroxo, instead of •OH, O2•-, and H2O2, are the primary oxidizing species in the oxidative damage to E. coli. Raman analysis further confirms the presence of both ≡CuII─OO• superoxo and ≡CuII─OOH peroxo on the surface of r-Cu2O. On the other hand, the NCP experiment reveals that Cu+, instead of Cu2+, also contributes to the antibacterial process. This study provides new insight into the antibacterial mechanisms of Cu2O.

Epidemiological characteristics and clinical antibiotic resistance analysis of Ureaplasma urealyticum infection among women and children in southwest China.

BACKGROUND: The aim of this study was to investigate the epidemiological characteristics and antibiotic resistance patterns of Ureaplasma urealyticum (UU) infection among women and children in southwest China. METHODS: A total of 8,934 specimens, including urogenital swabs and throat swabs were analyzed in this study. All samples were tested using RNA-based Simultaneous Amplification and Testing (SAT) methods. Culture and drug susceptibility tests were performed on UU positive patients. RESULTS: Among the 8,934 patients, the overall positive rate for UU was 47.92%, with a higher prevalence observed among women of reproductive age and neonates. The majority of UU positive outpatients were women of reproductive age (88.03%), while the majority of UU positive inpatients were neonates (93.99%). Overall, hospitalization rates due to UU infection were significantly higher in neonates than in women. Further analysis among neonatal inpatients revealed a higher incidence of preterm birth and low birth weight in UU positive inpatients (52.75% and 3.65%, respectively) than in UU negative inpatients (44.64% and 2.89%, respectively), especially in very preterm and extremely preterm neonates. Moreover, the incidence rate of bronchopulmonary dysplasia (BPD) among hospitalized neonatal patients was significantly higher in the UU positive group (6.89%) than in the UU negative group (4.18%). The drug susceptibility tests of UU in the neonatology, gynecology and obstetrics departments exhibited consistent sensitivity patterns to antibiotics, with high sensitivity to tetracyclines and macrolides, and low sensitivity to fluoroquinolones. Notably, UU samples collected from the neonatology department exhibited significantly higher sensitivity to azithromycin and erythromycin (93.8% and 92.9%, respectively) than those collected from the gynecology and obstetrics departments. CONCLUSIONS: This study enhances our understanding of the current epidemiological characteristics and antibiotic resistance patterns of UU infection among women and children in southwest China. These findings can aid in the development of more effective intervention, prevention and treatment strategies for UU infection.

Conduction system pacing upgrade versus biventricular pacing on pacemaker-induced cardiomyopathy: a retrospective observational study.

Objective: The feasibility of the conduction system pacing (CSP) upgrade as an alternative modality to the traditional biventricular pacing (BiVP) upgrade in patients with pacemaker-induced cardiomyopathy (PICM) remains uncertain. This study sought to compare two modalities of CSP (His bundle pacing (HBP) and left bundle branch pacing (LBBP)) with BiVP and no upgrades in patients with pacing-induced cardiomyopathy. Methods: This retrospective analysis comprised consecutive patients who underwent either BiVP or CSP upgrade for PICM at the cardiac department from 2017 to 2021. Patients with a follow-up period exceeding 12 months were considered for the final analysis. Results: The final group of patients who underwent upgrades included 48 individuals: 11 with BiVP upgrades, 24 with HBP upgrades, and 13 with LBBP upgrades. Compared to the baseline data, there were significant improvements in cardiac performance at the last follow-up. After the upgrade, the QRS duration (127.81 ± 31.89 vs 177.08 ± 34.35 ms, p < 0.001), NYHA class (2.28 ± 0.70 vs 3.04 ± 0.54, p < 0.05), left ventricular end-diastolic diameter (LVEDD) (54.08 ± 4.80 vs 57.50 ± 4.85 mm, p < 0.05), and left ventricular ejection fraction (LVEF) (44.46% ± 6.39% vs 33.15% ± 5.25%, p < 0.001) were improved. There was a noticeable improvement in LVEF in the CSP group (32.15% ± 3.22% vs 44.95% ± 3.99% (p < 0.001)) and the BiVP group (33.90% ± 3.09% vs 40.83% ± 2.99% (p < 0.001)). The changes in QRS duration were more evident in CSP than in BiVP (56.65 ± 11.71 vs 34.67 ± 13.32, p < 0.001). Similarly, the changes in LVEF (12.8 ± 3.66 vs 6.93 ± 3.04, p < 0.001) and LVEDD (5.80 ± 1.71 vs 3.16 ± 1.35, p < 0.001) were greater in CSP than in BiVP. The changes in LVEDD (p = 0.549) and LVEF (p = 0.570) were similar in the LBBP and HBP groups. The threshold in LBBP was also lower than that in HBP (1.01 ± 0.43 vs 1.33 ± 0.32 V, p = 0.019). Conclusion: The improvement of clinical outcomes in CSP was more significant than in BiVP. CSP may be an alternative therapy to CRT for patients with PICM. LBBP would be a better choice than HBP due to its lower thresholds.

Effect of ethanol on the elasticities of double-stranded RNA and DNA revealed by magnetic tweezers and simulations.

The elasticities of double-stranded (ds) DNA and RNA, which are critical to their biological functions and applications in materials science, can be significantly modulated by solution conditions such as ions and temperature. However, there is still a lack of a comprehensive understanding of the role of solvents in the elasticities of dsRNA and dsDNA in a comparative way. In this work, we explored the effect of ethanol solvent on the elasticities of dsRNA and dsDNA by magnetic tweezers and all-atom molecular dynamics simulations. We found that the bending persistence lengths and contour lengths of dsRNA and dsDNA decrease monotonically with the increase in ethanol concentration. Furthermore, the addition of ethanol weakens the positive twist-stretch coupling of dsRNA, while promotes the negative twist-stretch coupling of dsDNA. Counter-intuitively, the lower dielectric environment of ethanol causes a significant re-distribution of counterions and enhanced ion neutralization, which overwhelms the enhanced repulsion along dsRNA/dsDNA, ultimately leading to the softening in bending for dsRNA and dsDNA. Moreover, for dsRNA, ethanol causes slight ion-clamping across the major groove, which weakens the major groove-mediated twist-stretch coupling, while for dsDNA, ethanol promotes the stretch-radius correlation due to enhanced ion binding and consequently enhances the helical radius-mediated twist-stretch coupling.

Utilizing ultrasound combined with quinoa protein to improve the texture and rheological properties of Chinese style reduced-salt pork meatballs (lion's head).

This study aimed to investigate the effect of ultrasound treatment times (30 min and 60 min) and levels of quinoa protein (QPE) addition (1 % and 2 %) on the quality of Chinese style reduced-salt pork meatballs, commonly known as lion's head. The water-holding capacity (WHC), gel and rheology characteristics, and protein conformation were assessed. The results indicated that extending the ultrasound treatment time and elevating the quinoa protein content caused conspicuous improvements (P<0.05) in the cooking yield, WHC, textural characteristics, color difference, and salt-soluble protein (SSP) solubility of the meatballs. Furthermore, the structural alterations induced by the ultrasound treatment combined with quinoa protein addition included enhancement in ß-sheet, ß-turn, and random coil structure contents, along with a red-shift in the intrinsic fluorescence peak. Additionally, the storage (G') and loss modulus (G'') of the raw meatballs significantly enhanced (P<0.05), indicating a denser gel structure in parallel with the microstructure. In conclusion, the findings demonstrated that ultrasound combined with quinoa protein enhanced the WHC and texture properties of Chinese style reduced-salt pork meatballs by improving SSP solubility.

A multifunctional PEGylated liposomal-encapsulated sunitinib enhancing autophagy, immunomodulation, and safety in renal cell carcinoma.

BACKGROUND: Sunitinib is a multikinase inhibitor used to treat patients with advanced renal cell carcinoma (RCC). However, sunitinib toxicity makes it a double-edged sword. Potent immune modulation by sunitinib extends to nuclear interactions. To address these issues, there is an urgent need for delivery vectors suitable for sunitinib treatment. METHODS: We developed PEGylated liposomes as delivery vectors to precisely target sunitinib (lipo-sunitinib) to RCC tumors. Further investigations, including RNA sequencing (RNA-seq), were performed to evaluate transcriptomic changes in these pathways. DiI/DiR-labeled lipo-sunitinib was used for the biodistribution analysis. Flow cytometry and immunofluorescence (IF) were used to examine immune modulation in orthotopic RCC models. RESULTS: The evaluation of results indicated that lipo-sunitinib precisely targeted the tumor site to induce autophagy and was readily taken up by RCC tumor cells. In addition, transcriptomic assays revealed that following lipo-sunitinib treatment, autophagy, antigen presentation, cytokine, and chemokine production pathways were upregulated, whereas the epithelial-mesenchymal transition (EMT) pathway was downregulated. In vivo data provided evidence supporting the inhibitory effect of lipo-sunitinib on RCC tumor progression and metastasis. Flow cytometry further demonstrated that liposunitinib increased the infiltration of effector T cells (Teffs) and conventional type 1 dendritic cells (cDC1s) into the tumor. Furthermore, systemic immune organs such as the tumor-draining lymph nodes, spleen, and bone marrow exhibited upregulated anticancer immunity following lipo-sunitinib treatment. CONCLUSION: Our findings demonstrated that lipo-sunitinib is distributed at the RCC tumor site, concurrently inducing potent autophagy, elevating antigen presentation, activating cytokine and chemokine production pathways, and downregulating EMT in RCC cells. This comprehensive approach significantly enhanced tumor inhibition and promoted anticancer immune modulation.

Relationship of inflammatory indices with left atrial appendage thrombus or spontaneous echo contrast in patients with atrial fibrillation.

BACKGROUND: Inflammatory indices derived from complete blood tests have been reported to be associated with poor outcomes in patients with atrial fibrillation (AF). The data about the relationship between inflammatory indices and left atrial appendage thrombus (LAAT) or dense spontaneous echo contrast (SEC) are limited. AIM: To explore the value of inflammatory indices for predicting the presence of LAAT or dense SEC in nonvalvular AF patients. METHODS: A total of 406 patients with nonvalvular AF who underwent transesophageal echocardiography were included and divided into two groups based on the presence (study group) or absence (control group) of LAAT or dense SEC. Inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), were calculated from complete blood analysis. The associations of inflammatory indices with LAAT/dense SEC were analyzed using logistic regression. RESULTS: LAAT and dense SEC were detected in 11 (2.7%) and 42 (10.3%) patients, respectively. The PLR only showed an association with LAAT/dense SEC in the univariate model. Elevated NLR (odds ratio [OR] = 1.48, 95% confidence interval [CI]: 1.11-1.98, P = 0.007) and reduced LMR (OR = 0.59, 95%CI: 0.41-0.83, P = 0.003) were found to be independent risk factors for the presence of LAAT/dense SEC. The areas under the NLR and LMR curves for predicting LAAT/dense SEC were 0.73 (95%CI: 0.66-0.80, P < 0.001) and 0.73 (95%CI: 0.65-0.81, P < 0.001), respectively, while the cutoff values were 2.8 (sensitivity: 69.8%; specificity: 64.0%) and 2.4 (sensitivity: 71.7%; specificity: 60.6%), respectively. CONCLUSION: Increased NLR and decreased LMR may predict LAAT/dense SEC in patients with nonvalvular AF.

A Series of Lanthanide Coordination Polymers as Luminescent Sensors for Selective Detection of Inorganic Ions and Nitrobenzene.

Seven new lanthanide coordination polymers, namely [Ln(cpt)3H2O)]n(Ln = La (1), Pr (2), Sm (3), Eu (4), Gd (5), Dy (6), and Er (7)), which were synthesized under hydrothermal conditions using 4'-(4-(4-carboxyphenyloxy)phenyl)-4,2':6',4'-tripyridine (Hcpt) as the ligand. The crystal structures of these seven complexes were determined using single-crystal X-ray diffraction, and they were found to be isostructural, crystallizing in the triclinic P1- space group. The Ln(III) ions were nine-coordinated with tricapped trigonal prism coordination geometry. The Ln(III) cations were coordinated by carboxylic and pyridine groups from (cpt)- ligands, forming one-dimensional ring-chain structures. Furthermore, the luminescent properties of complexes 1-7 were investigated using fluorescent spectra in the solid state. The fluorescence sensing experiments demonstrated that complex 4 exhibits high selectivity and sensitivity for detecting Co2+, Cu2+ ions, and nitrobenzene. Moreover, complex 3 shows good capability for detecting Cu2+ ions and nitrobenzene. Additionally, the sensing mechanism was also thoroughly examined through theoretical calculations.

Role of TRPC6 in apoptosis of skeletal muscle ischemia/reperfusion injury.

BACKGROUND: Skeletal muscle ischaemia-reperfusion injury (IRI) is a prevalent condition encountered in clinical practice, characterised by muscular dystrophy. Owing to limited treatment options and poor prognosis, it can lead to movement impairments, tissue damage, and disability. This study aimed to determine and verify the influence of transient receptor potential canonical 6 (TRPC6) on skeletal muscle IRI, and to explore the role of TRPC6 in the occurrence of skeletal muscle IRI and the signal transduction pathways activated by TRPC6 to provide novel insights for the treatment and intervention of skeletal muscle IRI. METHODS: In vivo ischaemia/reperfusion (I/R) and in vitro hypoxia/reoxygenation (H/R) models were established, and data were comprehensively analysed at histopathological, cellular, and molecular levels, along with the evaluation of the exercise capacity in mice. RESULTS: By comparing TRPC6 knockout mice with wild-type mice, we found that TRPC6 knockout of TRPC6 could reduced skeletal muscle injury after I/R or H/R, of skeletal muscle, so as therebyto restoringe some exercise capacity inof mice. TRPC6 knockdown can reduced Ca2+ overload in cells, therebyo reducinge apoptosis. In additionAdditionally, we also found that TRPC6 functionsis not only a key ion channel involved in skeletal muscle I/R injury, but also can affects Ca2+ levels and then phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signalling pathway. by knocking downTherefore, knockdown of TRPC6, so as to alleviated the injury inducedcaused by skeletal muscle I/R or and H/R. CONCLUSIONS: These findingsdata indicate that the presence of TRPC6 exacerbatescan aggravate the injury of skeletal muscle injury after I/Rischemia/reperfusion, leading towhich not only causes Ca2+ overload and apoptosis., Additionally, it impairsbut also reduces the self- repair ability of cells by inhibiting the expression of the PI3K/Akt/mTOR signalling pathway. ETo exploringe the function and role of TRPC6 in skeletal muscle maycan presentprovide a novelew approachidea for the treatment of skeletal muscle ischemia/reperfusion injury.

Ubiquitin-induced RNF168 condensation promotes DNA double-strand break repair.

Rapid accumulation of repair factors at DNA double-strand breaks (DSBs) is essential for DSB repair. Several factors involved in DSB repair have been found undergoing liquid-liquid phase separation (LLPS) at DSB sites to facilitate DNA repair. RNF168, a RING-type E3 ubiquitin ligase, catalyzes H2A.X ubiquitination for recruiting DNA repair factors. Yet, whether RNF168 undergoes LLPS at DSB sites remains unclear. Here, we identified K63-linked polyubiquitin-triggered RNF168 condensation which further promoted RNF168-mediated DSB repair. RNF168 formed liquid-like condensates upon irradiation in the nucleus while purified RNF168 protein also condensed in vitro. An intrinsically disordered region containing amino acids 460-550 was identified as the essential domain for RNF168 condensation. Interestingly, LLPS of RNF168 was significantly enhanced by K63-linked polyubiquitin chains, and LLPS largely enhanced the RNF168-mediated H2A.X ubiquitination, suggesting a positive feedback loop to facilitate RNF168 rapid accumulation and its catalytic activity. Functionally, LLPS deficiency of RNF168 resulted in delayed recruitment of 53BP1 and BRCA1 and subsequent impairment in DSB repair. Taken together, our finding demonstrates the pivotal effect of LLPS in RNF168-mediated DSB repair.

Suppression of GATA3 promotes epithelial-mesenchymal transition and simultaneous cellular senescence in human extravillous trophoblasts.

The regulatory mechanism of the transcription factor GATA3 in the differentiation and maturation process of extravillous trophoblasts (EVT) in early pregnancy placenta, as well as its relevance to the occurrence of pregnancy disorders, remains poorly understood. This study leveraged single-cell RNA sequencing data from placental organoid models and placental tissue to explore the dynamic changes in GATA3 expression during EVT maturation. The expression pattern exhibited an initial upregulation followed by subsequent downregulation, with aberrant GATA3 localization observed in cases of recurrent miscarriage (RM). By identifying global targets regulated by GATA3 in primary placental EVT cells, JEG3, and HTR8/SVneo cell lines, this study offered insights into its regulatory mechanisms across different EVT cell models. Shared regulatory targets among these cell types and activation of trophoblast cell marker genes emphasized the importance of GATA3 in EVT differentiation and maturation. Knockdown of GATA3 in JEG3 cells led to repression of GATA3-induced epithelial-mesenchymal transition (EMT), as evidenced by changes in marker gene expression levels and enhanced migration ability. Additionally, interference with GATA3 accelerated cellular senescence, as indicated by reduced proliferation rates and increased activity levels for senescence-associated ß-galactosidase enzyme, along with elevated expression levels for senescence-associated genes. This study provides comprehensive insights into the dual role of GATA3 in regulating EMT and cellular senescence during EVT differentiation, shedding light on the dynamic changes in GATA3 expression in normal and pathological placental conditions.

Combined activation of artificial and natural ion channels for disrupting mitochondrial ion homeostasis towards effective postoperative tumor recurrence and metastasis suppression.

Rationale: Pharmacological targeting of mitochondrial ion channels is developing as a new direction in cancer therapy. The opening or closing of these channels can impact mitochondrial function and structure by interfering with intracellular ion homeostasis, thereby regulating cell fate. Nevertheless, their abnormal expression or regulation poses challenges in eliminating cancer cells, and further contributes to metastasis, recurrence, and drug resistance. Methods: We developed an engineered mitochondrial targeted delivery system with self-reinforcing potassium ion (K+) influx via amphiphilic mitochondrial targeting polymer (TMP) as carriers to co-deliver natural K+ channel agonists (Dinitrogen oxide, DZX) and artificial K+ channel molecules (5F8). Results: Using this method, DZX specifically activated natural K+ channels, whereas 5F8 assembled artificial K+ channels on the mitochondrial membrane, leading to mitochondrial K+ influx, as well as oxidative stress and activation of the mitochondrial apoptotic pathway. Conclusion: The synergistic effect of 5F8 and DZX presents greater effectiveness in killing cancer cells than DZX alone, and effectively inhibited tumor recurrence and lung metastasis following surgical resection of breast cancer tumors in animal models. This strategy innovatively integrates antihypertensive drugs with artificial ion channel molecules for the first time to effectively inhibit tumor recurrence and metastasis by disrupting intracellular ion homeostasis, which will provide a novel perspective for postoperative tumor therapy.

Glycyrrhetinic acid blocks SARS-CoV-2 infection by activating the cGAS-STING signalling pathway.

BACKGROUND AND PURPOSE: Traditional Chinese medicine (TCM) played an important role in controlling the COVID-19 pandemic, but the scientific basis and its active ingredients are still weakly studied. This study aims to decipher the underlying anti-SARS-CoV-2 mechanisms of glycyrrhetinic acid (GA). EXPERIMENTAL APPROACH: GA's anti-SARS-CoV-2 effect was verified both in vitro and in vivo. Homogeneous time-resolved fluorescence assays, biolayer interferometry technology, and molecular docking were employed to examine interactions of GA with human stimulator of interferon genes (hSTING). Immunofluorescence staining, western blot, and RT-qPCR were used to investigate nuclear translocation of interferon regulatory factor 3 (IRF3) and levels of STING target genes. Pharmacokinetics of GA was studied in mice. KEY RESULTS: GA could directly bind to Ser162 and Tyr240 residues of hSTING, thus up-regulating downstream targets and activation of the STING signalling pathway. Such activation is crucial for limiting the replication of SARS-CoV-2 Omicron in Calu-3 cells and protecting against lung injury induced by SARS-CoV-2 Omicron infection in K18-ACE2 transgenic mice. Immunofluorescence staining and western blot indicated that GA increased levels of phosphorylated STING, phosphorylated TANK-binding kinase-1, and cyclic GMP-AMP synthase (cGAS). Importantly, GA increased nuclear translocation of IRF3. Pharmacokinetic analysis of GA in mice indicated it can be absorbed into circulation and detected in the lung at a stable level. CONCLUSION AND IMPLICATIONS: Activation of the cGAS-STING pathway through the GA-STING-IRF3 axis is essential for the antiviral activity of GA in mice, providing new insights into the potential translation of GA for treating SARS-CoV-2 in patients.

Synthesis, Fluorescence, and Bioactivity of Novel Isatin Derivatives.

The isatin group is widespread in nature and is considered to be a privileged building block for drug discovery. In order to develop novel SHP1 inhibitors with fluorescent properties as tools for SHP1 biology research, this work designed and synthesized a series of isatin derivatives. The presentive compound 5a showed good inhibitory activity against SHP1PTP with IC50 of 11 ± 3 µM, displayed about 92% inhibitory rate against MV-4-11 cell proliferation at the concentration of 20 µM, exhibited suitable fluorescent properties with a long emission wavelength and a large Stokes shift, and presented blue fluorescent imaging in HeLa cells with low cytotoxicity. This study could offer chemical tool to further understand SHP1 biology and develop novel SHP1 inhibitors in therapy.

Systematic proteomics analysis revealed different expression of laminin interaction proteins in breast cancer: lower in luminal subtype and higher in claudin-low subtype.

Background: Breast cancer is a major public health concern. Proteomics enables identification of proteins with aberrant properties. Here, we identified proteins with abnormal expression levels in breast cancer tissues and systematically analyzed and validated the data to locate potential diagnostic and therapeutic targets. Methods: Protein expression level in breast cancer tissues and para-carcinoma tissues were detected by Isobaric Tags for Relative and Absolute Quantification (iTRAQ) technology and further screened through Gene Expression Profiling Interactive Analysis (GEPIA) database. Cellular components, protein domain and Reactome pathway analysis were performed to screen functional targets. Abnormal expression levels of functional targets were validated by Oncomine database, quantitative real time polymerase chain reaction (qRT-PCR) and proteomics detection. Protein correlation analysis was performed to explain the abnormal expression levels of potential targets in breast cancer. Results: Overall, 207 and 207 proteins were up- and down-regulated, respectively, in breast cancer tissues, and approximately 50% were also detected in the GEPIA database. The overlapping proteins were mainly extracellular proteins containing epidermal growth factor-like domain in leukocyte adhesion molecule (EGF-Lam) domain and enriched in laminin interaction pathway. Moreover, the downregulated laminin interaction proteins could be functional targets, which were also validated through Oncomine-Richardson and Oncomine-Curtis database. However, the lower expression level of laminin interaction proteins only fit for luminal breast cancer cells with no or low metastasis ability because the proteins achieved higher expression level in more invasive claudin-low breast cancer cells. In addition, when compared with corresponding in situ carcinoma tissues, above-mentioned proteins also showed higher expression levels in invasive carcinoma tissues. Finally, we have revealed the negative correlation between the laminin interaction proteins and the claudins. Conclusions: The laminin interaction protein, especially for laminins with ß1 and γ1 subunits and their integrin receptors with α1 and α6 subunits, showed lower expression levels in luminal breast cancer with no or lower metastatic ability, but showed higher expression levels in claudin-low breast cancer with higher metastatic ability; and their higher expression could be related to the low claudin expression.

[Preparation and characterization of co-loaded indocyanine green and elemene nano-emulsion in situ gel and its effect on proliferation of breast cancer MCF-7 cells].

This study aims to prepare co-loaded indocyanine green(ICG) and elemene(ELE) nano-emulsion(NE) in situ gel(ICG-ELE-NE-gel) and evaluate its physicochemical properties and antitumor activity in vitro. ICG-ELE-NE-gel was prepared by aqueous phase titration and cold solution methods, followed by characterization of the morphology, particle size, corrosion, and photothermal conversion characteristics. The human breast cancer MCF-7 cells were taken as the model, combined with 808 nm laser irradia-tion. Cell inhibition rate test and cell uptake test were performed. ICG-ELE-NE was spherical and uniform in size. The average particle size and Zeta potential were(85.61±0.35) nm and(-21.4±0.6) mV, respectively. The encapsulation efficiency and drug loading rate were 98.51%±0.39% and 10.96%±0.24%, respectively. ICG-ELE-NE-gel had a good photothermal conversion effect and good photothermal stability. The dissolution of ICG-ELE-NE-gel had both temperature and pH-responsive characteristics. Compared with free ELE, ICG-ELE-NE-gel combined with near-infrared light irradiation significantly enhanced the inhibitory effect on MCF-7 cells and could be uptaken in large amounts by MCF-7 cells. ICG-ELE-NE-gel was successfully prepared, and its antitumor activity was enhanced after 808 nm laser irradiation.

Application and prospect of BSA method based on bibliometrics in crop breeding.

In order to understand the progress and frontier in the application of BSA(bulked segregant analysis) method in crop breeding and to reflect objectively the contribution of different countries, institutions and researchers in this field at home and abroad, this study analyzed 2111 items in the WOS (Web of Science) database from 2000 to 2023 and 446 items in the CNKI (China National through Knowledge Infrastructure) database from 2003 to 2023, regarding the researches of the application of BSA in crop breeding, basing on bibliometric analysis methods using CiteSpace software including keyword co-occurrence analysis, highlight word analysis, keyword clustering analysis, clustering timeline analysis and author co-citation. The results showed that there was an consistent increasing trend in the publication number of the application of BSA in crop breeding both in the domestic and foreign journals year by year. Ranking of the top countries according to the number of publications was China, the United States and India. The Huazhong Agricultural University displayed the highest number of publications in the CNKI database, while the Chinese Academy of Agricultural Sciences was found to have the highest number of publications in the WOS database. The published articles related to the application of BSA in crop breeding abroad mainly focused on the disciplines such as plant science, agronomy, horticulture and genetics, while those in China mainly concentrated on such disciplines as plant science, plant protection, horticulture and biology. The top three authors in terms of influence in the field of appling BSA in crop breeding were Michelmore RW, Kosambi DD and Li H, while Michelmore RW, Lander ES and Li H had closer cooperations with other authors. The top three crops relating to the studies of BSA were rice(Oryza sativa), soybean(Glycine max), corn(Zea mays L.) with the hot spot traits of disease resistance and plant height domestically. The top three crops involving the studies of BSA were rice, Arabidopsis thaliana and wheat(Triticum aestivum L.) with hot spot traits of disease resistance abroad. Up to now, BSA was mainly used to localize and functionally verify the candidate genes linking target traits and the mutated genes in crops in the domestical documents, while the foreign published studies based on BSA were mainly focused on the fine mapping and functional verification of target trait genes aiming at the revelation of genetic mechanisms in crops. Research frontier analysis indicated that rice, peanuts(Arachis hypogaea L.), upland cotton(Gossypium hirsutum L.) would be the main objects of studies concerning application of BSA in crop breeding with the hot topics of crop mutants and crop metabolites in the future.

Polar Bloch points in strained ferroelectric films.

Topological domain structures have drawn great attention as they have potential applications in future electronic devices. As an important concept linking the quantum and classical magnetism, a magnetic Bloch point, predicted in 1960s but not observed directly so far, is a singular point around which magnetization vectors orient to nearly all directions. Here we show polar Bloch points in tensile-strained ultrathin ferroelectric PbTiO3 films, which are alternatively visualized by phase-field simulations and aberration-corrected scanning transmission electron microscopic imaging. The phase-field simulations indicate local steady-state negative capacitance around the Bloch points. The observation of polar Bloch points and their emergent properties consequently implies novel applications in future integrated circuits and low power electronic devices.