Integration of surface swab with optical microscopy for detection and quantification of bacterial cells from stainless-steel surfaces.

Swab sampling is a common method for recovering microbes on various environmental surfaces. Its successful application for a specific target depends on the proper swab method and the following detection assay. Herein, we evaluated critical factors influencing surface swab sampling, aiming to achieve the optimal detection and quantification performance of optical detection for bacterial cells on stainless-steel surfaces. Our results showed the recovery rate of Salmonella enterica (SE1045) cells from the 10×10 cm2 stainless-steel surface reached up to 92.71±2.19% when using ammonia bicarbonate-moistened polyurethane foam swabs for gentle collection, followed by ultrasound-assisted release in NH4HCO3 solution. Among the six different foam swabs, the Puritan™ Sterile Large Foam Swab contributed the lowest background noise and highest recovery efficiency when integrated with the optical detection assay. Notably, our method exhibited a strong linear relationship (r2 = 0.9983) between the detected cell numbers and the theoretical number of SE1045 cells seeded on surfaces in the range of 104-107 CFU, with a limit of detection of 7.2×104 CFU 100 cm-2. This integration was completed within 2 hours, exhibiting the applicable potential in various settings.

Additional Lesion Sets in Ablation of Outflow Tract Premature Ventricular Contractions: A Randomized Clinical Trial.

Importance: Recurrence remains a challenge after ablation of outflow tract premature ventricular contractions (OT-PVCs). Although adding additional lesions next to the index effective ablation site is sometimes performed to reinforce the ablation, it remains uncertain whether this approach is effective. Objective: To test the hypothesis that additional ablation lesions would reduce the recurrence rate compared with single-point ablation at the index effective site for the ablation of OT-PVCs. Design, Setting, and Participants: This study was a multicenter, prospective, randomized clinical trial. Patients receiving their first catheter ablation for OT-PVCs were enrolled from 18 hospitals in China between October 2021 and February 2023. Scheduled follow-up duration was 3 months after the procedure. Intervention: After identifying the target point and eliminating the PVC by a single-point ablation, patients were randomized 1:1 into an additional ablation group or a control group. Main Outcomes and Measures: The primary end point of the study was freedom from PVC recurrence (≥80% reduction of PVC burden, which is the number of PVCs in 24 hours/total heartbeats in 24 hours × 100%) from baseline to 3 months postprocedure. Results: Of 308 patients enrolled in the study, 286 (mean [SD] age, 49.2 [14.6] years; 173 female [60.5%]) were randomized to the additional ablation or the control group. The additional ablation group had a mean (SD) of 6.3 (1.1) radiofrequency applications, whereas the control group (single-point ablation group) had a mean (SD) of 1 (0) radiofrequency application. After a median (IQR) follow-up of 3.2 (0) months, the rate of freedom from PVCs was significantly higher in the additional ablation group (139 of 142 [97.9%]) compared with the control group (115 of 139 [82.7%]; P < .001). Patients in the additional ablation group also had a more substantial reduction in PVC burden than the control group (mean [SD] reduction, 23.0% [10.5%] vs 19.0% [10.4%]; P = .002). There were no severe periprocedural complications in either group. Conclusions and Relevance: This randomized clinical trial showed a benefit of additional ablation in reducing the recurrence of OT-PVCs compared with the single-point ablation strategy, without increased complication risk. Additional ablations surrounding the index effective ablation point should be considered in OT-PVC ablation. Trial Registration: Chinese Clinical Trials Registry Identifier: ChiCTR2200055340.

Oregano essential oil-infused mucin microneedle patch for the treatment of hypertrophic scar.

Hypertrophic scar (HS) manifests as abnormal dermal myofibroblast proliferation and excessive collagen deposition, leading to raised scars and significant physical, psychological, and financial burdens for patients. HS is difficult to cure in the clinic and current therapies lead to recurrence, pain, and side effects. In this study, a natural amphiphilic polymer mucin is used to prepare a dissolving microneedle (muMN) that is loaded with oregano essential oil (OEO) for HS therapy. muMN exhibits sufficient skin/scar tissue penetration, quick skin recovery time after removal, good loading of natural essential oil, fast dissolution and detachment from the base layer, and good biocompatibility to applied skin. In the rabbit HS model, OEO@muMN shows a significant reduction in scar thickness, epidermal thickness index, and scar elevation index. OEO@muMN also attenuates the mean collagen area fraction and decreases the number of capillaries in scar tissues. Biochemical Assay reveals that OEO@muMN significantly inhibits the expression of transforming growth factor-ß1 (TGF-ß1) and hydroxyproline (HYP). In summary, this study demonstrates the feasibility and good efficacy of using the anti-proliferative and anti-oxidative OEO for HS treatment. OEO@muMN is an efficient formulation that holds the potential for clinical anti-HS application. muMN is an efficient platform to load and apply essential oils transdermally.

Optical detection and enumeration of Escherichia coli and Salmonella enterica using a low-magnification light microscope.

A rapid and cost-effective method for detecting bacterial cells from surfaces is critical to food safety, clinical hygiene, and pharmacy quality. Herein, we established an optical detection method based on a gold chip coating with 3-mercaptophenylboronic acid (3-MPBA) to capture bacterial cells, which allows for the detection and quantification of bacterial cells with a standard light microscope under low-magnification (10×) objective lens. Then, integrate the developed optical detection method with swab sampling to detect bacterial cells loading on stainless-steel surfaces. Using Salmonella enterica (SE1045) and Escherichia coli (E. coli OP50) as model bacterial cells, we achieved a capture efficiency of up to 76.0 ± 2.0 % for SE1045 cells and 81.1 ± 3.3 % for E. coli OP50 cells at 103 CFU/mL upon the optimized conditions, which slightly decreased with the increasing bacterial concentrations. Our assay showed good linear relationships between the concentrations of bacterial cells with the cell counting in images in the range of 103 -107 CFU/mL for SE1045, and 103 -108 CFU/mL for E. coli OP50 cells. The limit of detection (LOD) was 103 CFU/mL for both SE1045 and E. coli OP50 cells. A further increase in sensitivity in detecting E. coli OP50 cells was achieved through a heat treatment, enabling the LOD to be reduced as low as 102 CFU/mL. Furthermore, a preliminary application succeeded in assessing bacterial contamination on stainless-steel surfaces following integration with the approximately 40 % recovery rate, suggesting prospects for evaluating the bacteria from surfaces. The entire process was completed within around 2 h, costing merely a few dollars per sample. Considering the low cost of standard light microscopes, our method holds significant potential for practical industrial applications in bacterial contamination control on surfaces, especially in low-resource settings.

Unveiling the charge storage mechanisms of Co-based perovskite fluoride in a mild aqueous electrolyte.

This study is an in-depth exploration of the charge storage mechanisms of KCoF3 in 1 M Na2SO4 mild aqueous electrolytes via an array of ex situ/in situ physicochemical/electrochemical methods, especially the electrochemical quartz crystal microbalance (EQCM) technique, showing a combination of conversion, insertion/extraction and adsorption mechanisms. Specifically, during the first charge phase, Co(OH)2 is formed/oxidized into amorphous CoOOH and Co3O4, and then CoOOH undergoes partial proton extraction to yield CoO2, which is simultaneously accompanied by the transformation of Co3O4 into CoOOH and (hydrated) CoO2. During the first discharge process, the partial insertion of H+ into (hydrated) CoO2 leads to the formation of CoOOH and Co3O4, with the conversion of Co3O4 into CoOOH and both Co3O4 and CoOOH undergoing further transformations into (hydrated) Co(OH)2via the insertion of H+. This work offers valuable references for the development of aqueous energy storage.

Enhancing the Viability of a Small Giant Panda Population Through Individual Introduction From a Larger Conspecific Group: A Scientific Simulation Study.

Currently, nearly 70% of giant panda populations are facing survival challenges. The introduction of wild individuals can bring vitality to them. To explore this possibility, we hypothetically introduced giant pandas from Tangjiahe and Wanglang into Liziping and Daxiangling Nature Reserves. We collected feces from these areas and analyzed the genetic diversity and population viability before and after introduction using nine microsatellite loci. The results showed the genetic level and viability of the large populations were better than the small populations. We investigated the effects of time intervals (2a, 5a, and 10a; year: a) and gender combinations (female: F; male: M) on the rejuvenation of small populations. Finally, five introduction plans (1F/2a, 2F/5a, 1F1M/5a, 3F/10a, and 2F1M/10a) were obtained to make Liziping meet the long-term survival standard after 100 years, and six plans (1F/2a, 2F/5a, 1F1M/5a, 4F/10a, 3F1M/10a, and 2F2M/10a) were obtained in Daxiangling. The more females were introduced, the greater the impact on the large populations. After introducing individuals, the number of alleles and expected heterozygosity of the Liziping population are at least 6.667 and 0.688, and for the Daxiangling population, they are 7.111 and 0.734, respectively. Our study provides theoretical support for the translocation of giant pandas, a reference for the restoration of other endangered species worldwide.

Epitranscriptomic m5C methylation of SARS-CoV-2 RNA regulates viral replication and the virulence of progeny viruses in the new infection.

While the significance of N6-methyladenosine (m6A) in viral regulation has been extensively studied, the functions of 5-methylcytosine (m5C) modification in viral biology remain largely unexplored. In this study, we demonstrate that m5C is more abundant than m6A in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and provide a comprehensive profile of the m5C landscape of SARS-CoV-2 RNA. Knockout of NSUN2 reduces m5C levels in SARS-CoV-2 virion RNA and enhances viral replication. Nsun2 deficiency mice exhibited higher viral burden and more severe lung tissue damages. Combined RNA-Bis-seq and m5C-MeRIP-seq identified the NSUN2-dependent m5C-methylated cytosines across the positive-sense genomic RNA of SARS-CoV-2, and the mutations of these cytosines enhance RNA stability. The progeny SARS-CoV-2 virions from Nsun2 deficiency mice with low levels of m5C modification exhibited a stronger replication ability. Overall, our findings uncover the vital role played by NSUN2-mediated m5C modification during SARS-CoV-2 replication and propose a host antiviral strategy via epitranscriptomic addition of m5C methylation to SARS-CoV-2 RNA.

Association between the triglyceride glucose-body mass index and future cardiovascular disease risk in a population with Cardiovascular-Kidney-Metabolic syndrome stage 0-3: a nationwide prospective cohort study.

BACKGROUND: The American Heart Association (AHA) has recently introduced the concept of Cardiovascular-Kidney-Metabolic (CKM) syndrome, which is the result of an increasing emphasis on the interplay of metabolic, renal and cardiovascular diseases (CVD). Furthermore, there is substantial evidence of a correlation between the triglyceride glucose-body mass index (TyG-BMI ) and CVD as an assessment of insulin resistance (IR). However, it remains unknown whether this correlation exists in population with CKM syndrome. METHODS: All data for this study were obtained from the China Health and Retirement Longitudinal Study (CHARLS). The exposure was the participants' TyG-BMI at baseline, which was calculated using a combination of triglycerides (TG), fasting blood glucose (FBG) and body mass index (BMI). The primary outcome was CVD, which were determined by the use of a standardised questionnaire during follow-up. To examine the relationship between TyG-BMI and CVD incidence in population with CKM syndrome, both Cox regression analyses and restricted cubic spline (RCS) regression analyses were performed. RESULTS: A total of 7376 participants were included in the final analysis. Of these, 1139, 1515, 1839, and 2883 were in CKM syndrome stages 0, 1, 2, and 3, respectively, at baseline. The gender distribution was 52.62% female, and the mean age was 59.17 ± 9.28 (years). The results of the fully adjusted COX regression analyses indicated that there was a 6.5% increase in the risk of developing CVD for each 10-unit increase in TyG-BMI,95% confidence interval (CI):1.041-1.090. The RCS regression analyses demonstrated a positive linear association between TyG-BMI and the incidence of CVD in the CKM syndrome population (P for overall < 0.001, P for nonlinear = 0.355). CONCLUSIONS: This cohort study demonstrated a positive linear association between TyG-BMI index and increased CVD incidence in a population with CKM syndrome stage 0-3. This finding suggests that enhanced assessment of TyG-BMI index may provide a more convenient and effective tool for individuals at risk for CVD in CKM syndrome stage 0-3.

Thiol-chromene click reaction-triggered mitochondria-targeted ratiometric fluorescent probe for intracellular biothiol imaging.

Chromene as the efficient biothiol recognition site was widely used to develop fluorescent probes based on thiol-chromene click reaction. However, chromene-based fluorescent probes with the both properties of ratiometric measurement and mitochondria-targeted function have not been reported and remain challenging. In this paper, we skillfully designed and synthesized the first mitochondria-targeted ratiometric fluorescent probe (Probe 1) for biothiols based on chromene. Upon addition of biothiols (Cys, Hcy, and GSH), the absorption and fluorescence spectra of Probe 1 changed from 490 to 426 nm and from 567 to 498 nm respectively, accompanied by color changes from orange to pale yellow under natural light and from orange to blue under a 365-nm UV lamp, which can be attributed to the click reaction of biothiols with α,ß-unsaturated ketone of chromene moiety, subsequent pyran ring-opening, and phenol formation as well as 1,6-elimination of p-hydroxybenzyl moiety. Probe 1 not only exhibited high sensitivity (LODs of 149 nM, 133 nM, and 116 nM for Cys, GSH, and Hcy respectively), rapid response, and excellent selectivity for biothiols (Cys, Hcy, and GSH), but also could target in mitochondria and ratiometrically image the fluctuation of intracellular biothiols. Moreover, the novel design strategy of modifying chromene to the N atom of pyridine was proposed for the first time.

Persistent glucose consumption under antibiotic treatment protects bacterial community.

Antibiotics typically induce major physiological changes in bacteria. However, their effect on nutrient consumption remains unclear. Here we found that Escherichia coli communities can sustain normal levels of glucose consumption under a broad range of antibiotics. The community-living resulted in a low membrane potential in the bacteria, allowing slow antibiotic accumulation on treatment and better adaptation. Through multi-omics analysis, we identified a prevalent adaptive response characterized by the upregulation of lipid synthesis, which substantially contributes to sustained glucose consumption. The consumption was maintained by the periphery region of the community, thereby restricting glucose penetration into the community interior. The resulting spatial heterogeneity in glucose availability protected the interior from antibiotic accumulation in a membrane potential-dependent manner, ensuring rapid recovery of the community postantibiotic treatment. Our findings unveiled a community-level antibiotic response through spatial regulation of metabolism and suggested new strategies for antibiotic therapies.

Spatially structured exchange of metabolites enhances bacterial survival and resilience in biofilms.

Biofilm formation enhances bacterial survival and antibiotic tolerance, but the underlying mechanisms are incompletely understood. Here, we show that biofilm growth is accompanied by a reduction in bacterial energy metabolism and membrane potential, together with metabolic exchanges between the inner and outer regions in biofilms. More specifically, nutrient-starved cells in the interior supply amino acids to cells in the periphery, while peripheral cells experience a decrease in membrane potential and provide fatty acids to interior cells. Fatty acids facilitate the repair of starvation-induced membrane damage in inner cells and enhance their survival in the presence of antibiotics. Thus, metabolic exchanges between inner and outer cells contribute to survival of the nutrient-starved inner cells and contribute to antibiotic tolerance within the biofilm.

Association of mutations in Mycobacterium tuberculosis complex (MTBC) respiration chain genes with hyper-transmission.

BACKGROUND: The respiratory chain plays a key role in the growth of Mycobacterium tuberculosis complex (MTBC). However, the exact regulatory mechanisms of this system still need to be elucidated, and only a few studies have investigated the impact of genetic mutations within the respiratory chain on MTBC transmission. This study aims to explore the impact of respiratory chain gene mutations on the global spread of MTBC. RESULTS: A total of 13,402 isolates of MTBC were included in this study. The majority of the isolates (n = 6,382, 47.62%) belonged to lineage 4, followed by lineage 2 (n = 5,123, 38.23%). Our findings revealed significant associations between Single Nucleotide Polymorphisms (SNPs) of specific genes and transmission clusters. These SNPs include Rv0087 (hycE, G178T), Rv1307 (atpH, C650T), Rv2195 (qcrA, G181C), Rv2196 (qcrB, G1250T), Rv3145 (nuoA, C35T), Rv3149 (nuoE, G121C), Rv3150 (nuoF, G700A), Rv3151 (nuoG, A1810G), Rv3152 (nuoH, G493A), and Rv3157 (nuoM, A1243G). Furthermore, our results showed that the SNPs of atpH C73G, atpA G271C, qcrA G181C, nuoJ G115A, nuoM G772A, and nuoN G1084T were positively correlated with cross-country transmission clades and cross-regional transmission clades. CONCLUSIONS: Our study uncovered an association between mutations in respiratory chain genes and the transmission of MTBC. This important finding provides new insights for future research and will help to further explore new mechanisms of MTBC pathogenicity. By uncovering this association, we gain a more complete understanding of the processes by which MTBC increases virulence and spread, providing potential targets and strategies for preventing and treating tuberculosis.

Phosphorescent PdII-PdII Emitter-Based Red OLEDs with an EQEmax of 20.52.

Three dinuclear Pd(II) complexes (1, 2, and 3) with intense red phosphorescence at room temperature are here synthesized using strong ligand field strength compounds. All three complexes are characterized by nuclear magnetic resonance, high-resolution mass spectrometry, and elemental analyses. Complexes 2 and 3 are characterized by single-crystal X-ray diffraction. The crystalline data of 2 and 3 reveal complex double-layer structures, with Pd-Pd distances of 2.8690(9) Å and 2.8584(17) Å, respectively. Furthermore, complexes 1, 2, and 3 show phosphorescence at room temperature in their solid states at the wavelengths of 678, 601, and 672 nm, respectively. In addition, they show phosphorescence at 634, 635, and 582 nm, respectively, in the 2 wt.% (PMMA) films, and phosphorescence at 670, 675, and 589 nm, respectively, in the deoxygenated CH2Cl2 solutions. Among three complexes, complex 1 shows red emission at 634 nm with phosphorescent quantum yield Ф = 67% in the 2 wt.% PMMA film. Furthermore, complex 1-based organic light-emitting diode is fabricated using a vapor-phase deposition process, and their maximum external quantum efficiency reaches 20.52%, which is the highest percentage obtained by using the dinuclear Pd(II) complex triplet emitters with the CIE coordinates of (0.62, 0.38).

Deciphering the Relationship between Cell Growth and Cell Cycle in Individual Escherichia coli Cells by Flow Cytometry.

Accurate coordination of chromosome replication and cell division is essential for cellular processes, yet the regulatory mechanisms governing the bacterial cell cycle remain contentious. The lack of quantitative data connecting key cell cycle players at the single-cell level across large samples hinders consensus. Employing high-throughput flow cytometry, we quantitatively correlated the expression levels of key cell cycle proteins (FtsZ, MreB, and DnaA) with DNA content in individual bacteria. Our findings reveal distinct correlations depending on the chromosome number (CN), specifically whether CN ≤2 or ≥4, unveiling a mixed regulatory scenario in populations where CN of 2 or 4 coexist. We observed function-dependent regulations for these key proteins across nonoverlapping division cycles and various nutrient conditions. Notably, a logarithmic relationship between total protein content and replication origin number across nutrient conditions suggests a unified mechanism governing cell cycle progression, confirming the applicability of Schaechter's growth law to cells with CN ≥4. For the first time, we established a proportional relationship between the synthesis rates of key cell cycle proteins and chromosome dynamics in cells with CN ≥4. Drug experiments highlighted CN 2 and 4 as pivotal turning points influencing cellular resource allocation. This high-throughput, single-cell analysis provides interconnected quantitative insights into key molecular events, facilitating a predictive understanding of the relationship between cell growth and cell cycle.

An azaryl-ketone-based thermally activated delayed fluorophore with aggregation-induced emission for efficient organic light-emitting diodes with slow efficiency roll-offs.

Achieving the concurrent manifestation of thermally activated delayed fluorescence (TADF) and aggregation-induced emission (AIE) within a single molecular system is highly sought after for organic light-emitting diodes (OLEDs), yet remains rare. In this study, we present a novel TADF-AIE dye, named PQMO-PXZ, which has been designed, synthesized, and systematically characterized. Our comprehensive investigation, which includes structural analysis, theoretical calculations, and optical studies, evaluates the potential of PQMO-PXZ for integration into OLEDs. Unlike existing azaryl-ketone-based emitters, PQMO-PXZ exhibits red-shifted emission and enhanced luminescence efficiency, due to its rigid structure and strong intramolecular charge transfer characteristics. Significantly, PQMO-PXZ demonstrates pronounced AIE properties and TADF with a short delayed lifetime. When utilized as the emissive core, OLED devices based on PQMO-PXZ achieve a respectable external quantum efficiency of up to 11.8% with minimal efficiency roll-off, underscoring PQMO-PXZ's promise as a highly efficient candidate for OLED applications.

Myocardial work alterations with progressive left ventricular hypertrophy in patients with hypertension.

Left ventricular (LV) hypertrophy (LVH) is frequently observed in patients with hypertension (HTN). LV myocardial work (MW) has recently emerged as a non-invasive method to assess systolic myocardial deformation relative to afterload conditions. The authors investigated the characteristics of myocardial work with different degrees of LVH in HTN patients. From December 2020 to February 2024, 255 HTN patients and 26 healthy controls undergoing transthoracic echocardiography were included in the current study. Hypertension patients were divided into quintile groups based on left ventricular mass index (LVMI), for the first to fourth LVMI quantiles, global work index (GWI) and global constructive work (GCW) were higher compared to the control group, but the difference was not statistically significant. In the sixth LVMI quantile, GWI and GCW showed a significant decrease. The restricted cubic splines showed that both GWI and GCW exhibited an inverted U-shaped relationship with LVMI. A LVMI of >151.39 g/m2 could accurately predict reduction both in GWI and GCW (Sensitivity: 0.78, Specificity: 0.89, AUC: 0.90, P < .001; Sensitivity: 0.81, Specificity: 0.92, AUC: 0.92, P < .001, respectively). As LVH progressed in HTN patients, both GWI and GCW initially demonstrated an increase, followed by a subsequent decrease. Myocardial work provides additional insights into assessment of cardiac function in HTN patients.

A new dicyanophenanthrene-based thermally activated delayed fluorophore: Design, synthesis, photophysical study, and electroluminescence application.

A novel thermally activated delayed fluorescence (TADF) emitter, DCNP-SCF, is developed based on a dicyanophenanthrene acceptor. DCNP-SCF is prepared by a simple C-N coupling reaction. Its thermal, theoretical, photophysical, and electroluminescent properties are investigated, emphasizing its potential in organic electroluminescence devices. DCNP-SCF demonstrates highly distorted donor-acceptor conformation, facilitating significant TADF for efficient triplet harvesting in electroluminescence devices. Additionally, due to the moderate electron push-pull effect, DCNP-SCF exhibits appropriate intramolecular charge transfer for considerable photoluminescence quantum yield for electroluminescence applications.

Can low-carbon transportation construction improve urban green total factor productivity? A quasi-natural experiment based on 282 prefecture-level cities in China.

Total factor productivity in the green economy is a major step forward in fostering robust growth in the economy. Urban green total factor productivity (GTFP) may be increased and carbon emissions decreased through the low-carbon transformation of the transportation sector. To analyze how the pilot policy of low-carbon transportation system construction affects urban GTFP, this study builds a DID model and a spatial Durbin model using panel data from 282 Chinese cities between 2006 and 2021. The findings show that low-carbon transportation systems boost urban GTFP. In addition, the mechanism test shows that low-carbon transportation development increases urban GTFP by optimizing urban industrial structure, expediting economic agglomeration, and encouraging technological innovation. Lastly, the geographical correlation test shows that GTFP is geographically associated and that spatial spillover reduces the impact of low-carbon transportation growth on GTFP. The findings affirm the need to vigorously promote low-carbon transportation systems to aid in the achievement of the carbon neutrality target.

Therapeutic efficacy of ECs Foxp1 targeting Hif1α-Hk2 glycolysis signal to restrict angiogenesis.

Endothelial cells (ECs) rely on glycolysis for energy production to maintain vascular homeostasis and the normalization of hyperglycolysis in tumor vessels has recently gained attention as a therapeutic target. We analyzed the TCGA database and found reduced Foxp1 expression in lung carcinoma. Immunostaining demonstrated reduced expression more restricted at tumor vascular ECs. Therefore, we investigated the function and mechanisms of Foxp1 in EC metabolism for tumor angiogenesis required for tumor growth. EC-Foxp1 deletion mice exhibited a significant increase of tumor and retinal developmental angiogenesis and Hif1α was identified as Foxp1 target gene, and Hk2 as Hif1α target gene. The Foxp1-Hif1α-Hk2 pathway in ECs is important in the regulation of glycolytic metabolism to govern tumor angiogenesis. Finally, we used genetic deletion of EC-Hif1α and RGD-peptide nanoparticles EC target delivery of Hif1α/Hk2-siRNAs to knockdown gene expression which reduced the tumor EC hyperglycolysis state and restricted angiogenesis for tumor growth. This study advances our understanding of EC metabolism for tumor angiogenesis, and meanwhile provides evidence for future therapeutic intervention of hyperglycolysis in tumor ECs for suppression of tumor growth.

Biomimetic nanomedicine cocktail enables selective cell targeting to enhance ovarian Cancer chemo- and immunotherapy.

Ovarian cancer is one of the deadliest cancers, and combined chemo- and immunotherapies are potential strategies to combat it. However, the anti-cancer efficacy of the combined therapies may be limited by the non-selective co-delivery of chemotherapy and immunotherapy. Herein, a combined chemo- and immunotherapy is designed to selectively target ovarian tumor (ID8) cells and dendritic cells (DCs) using ID8 cell membrane (IM) and bacterial outer membrane vesicles (OMVs), respectively. Doxorubicin (DOX) and Ovalbumin (OVA) peptide (OVA257-264) are chosen as model chemotherapy and immunotherapy agents, respectively. A DNA nanocube capable of easily loading DOX or OVA257-264 is chosen as the carrier. Firstly, the DNA nanocube is used to load DOX or OVA257-264 to prepare cube-DOX or cube-OVA. This nanocube was then encapsulated with IM to form IM@Cube-DOX and with OMV to form OMV@Cube-OVA. IM@Cube-DOX can be selectively taken up by ID8 cells, leading to effective cell killing, while OMV@Cube-OVA targets and activates DC2.4 cells in vitro. Both IM@Cube-DOX and OMV@Cube-OVA show increased accumulation at ID8 tumors in C57BL/6 mice. Combined IM@Cube-DOX + OMV@Cube-OVA therapy demonstrates better anti-tumor efficacy than non-selective delivery methods such as OMV@(Cube-DOX + Cube-OVA) or IM@(Cube-DOX + Cube-OVA) in ID8-OVA tumor-bearing mice. In conclusion, this study demonstrates a biomimetic delivery strategy that enables selective drug delivery to tumor cells and DCs, thereby enhancing the anti-tumor efficacy of combined chemo- and immunotherapy through the selective delivery strategy.