Development of Aptamer-DNAzyme based metal-nucleic acid frameworks for gastric cancer therapy.

The metal-nucleic acid nanocomposites, first termed metal-nucleic acid frameworks (MNFs) in this work, show extraordinary potential as functional nanomaterials. However, thus far, realized MNFs face limitations including harsh synthesis conditions, instability, and non-targeting. Herein, we discover that longer oligonucleotides can enhance the synthesis efficiency and stability of MNFs by increasing oligonucleotide folding and entanglement probabilities during the reaction. Besides, longer oligonucleotides provide upgraded metal ions binding conditions, facilitating MNFs to load macromolecular protein drugs at room temperature. Furthermore, longer oligonucleotides facilitate functional expansion of nucleotide sequences, enabling disease-targeted MNFs. As a proof-of-concept, we build an interferon regulatory factor-1(IRF-1) loaded Ca2+/(aptamer-deoxyribozyme) MNF to target regulate glucose transporter (GLUT-1) expression in human epidermal growth factor receptor-2 (HER-2) positive gastric cancer cells. This MNF nanodevice disrupts GSH/ROS homeostasis, suppresses DNA repair, and augments ROS-mediated DNA damage therapy, with tumor inhibition rate up to 90%. Our work signifies a significant advancement towards an era of universal MNF application.

Optimizing hydropower scheduling through accurate power load prediction: A practical case study.

Hydropower stations that are part of the grid system frequently encounter challenges related to the uneven distribution of power generation and associated benefits, primarily stemming from delays in obtaining timely load data. This research addresses this issue by developing a scheduling model that combines power load prediction and dual-objective optimization. The practical application of this model is demonstrated in a real-case scenario, focusing on the Shatuo Hydropower Station in China. In contrast to current models, the suggested model can achieve optimal dispatch for grid-connected hydropower stations even when power load data is unavailable. Initially, the model assesses various prediction models for estimating power load and subsequently incorporates the predictions into the GA-NSGA-II algorithm, specifically an enhanced elite non-dominated sorting genetic algorithm. This integration is performed while considering the proposed objective functions to optimize the discharge flow of the hydropower station. The outcomes reveal that the CNN-GRU model, denoting Convolutional Neural Network-Gated Recursive Unit, exhibits the highest prediction accuracy, achieving R-squared and RMSE (i.e., Root Mean Square Error) values of 0.991 and 0.026, respectively. The variance between scheduling based on predicted load values and actual load values is minimal, staying within 5 (m3/s), showcasing practical effectiveness. The optimized scheduling outcomes in the real case study yield dual advantages, meeting both the demands of ship navigation and hydropower generation, thus achieving a harmonious balance between the two requirements. This approach addresses the real-world challenges associated with delayed load data collection and insufficient scheduling, offering an efficient solution for managing hydropower station scheduling to meet both power generation and navigation needs.

Efficacy and safety of Shen Gui capsules for chronic heart failure: a systematic review and meta-analysis.

Background: Although Shen Gui capsules (SGCP) are widely used as an adjuvant treatment for chronic heart failure (CHF), their clinical efficacy and safety remain controversial. Purpose: To assess the efficacy and safety of SGCP in the treatment of CHF through a systematic review and meta-analysis, to provide high-quality evidence for evidence-based medicine. Methods: Seven databases were searched for randomized controlled trials (RCTs) assessing SGCP for CHF, from inception to 9 January 2023. RCT quality of evidence was evaluated using the Cochrane Handbook for the Evaluation of Intervention Systems to assess risk of bias and Grading of Recommendations Assessment, Development, and Evaluation. A meta-analysis with subgroup and sensitivity analyses was performed using Review Manager 5.4 and Stata 12. Results: Nine RCTs representing 888 patients with CHF were included in the review. Meta-analysis revealed that SGCP combined with conventional heart failure therapy is more advantageous for improving left ventricular ejection fraction [LVEF; mean difference (MD) = 5.26, 95% confidence interval (CI) (3.78, 6.74), p < 0.0000] and increasing effective rate [relative risk (RR) = 1.21, 95%CI (1.14, 1.29), p < 0.001] compared with conventional therapy alone. The experimental treatment also reduced brain natriuretic peptide [MD = -100.15, 95%CI (-157.83, -42.47), p = 0.0007], left ventricular end-diastolic diameter [MD = -1.93, 95%CI (-3.22, -0.64), p = 0.003], and hypersensitive C-reactive protein [MD = -2.70, 95%CI (-3.12,-2.28), p < 0.001] compared with the control group. However, there was not a statistically significant difference in tumor necrosis factor-α [MD = -14.16, 95%CI (-34.04, 5.73), p = 0.16] or left ventricular end-systolic diameter [MD = -1.56, 95%CI (-3.13, 0.01), p = 0.05]. Nor was there a statistically significant between-groups difference in incidence of adverse events (p > 0.05). Conclusion: SGCP combined with conventional heart failure therapy can improve LVEF and increase the effective rate to safely treat patients with CHF. However, further high-quality studies are needed to confirm these findings, due to the overall low quality of evidence in this literature.Clinical Trial Registration: https://www.crd.york.ac.uk/PROSPERO/logout.php, PROSPERO [CRD42023390409].

Potential electron acceptors for ammonium oxidation in wastewater treatment system under anoxic condition: A review.

Anaerobic ammonium oxidation has been considered as an environmental-friendly and energy-efficient biological nitrogen removal (BNR) technology. Recently, new reaction pathway for ammonium oxidation under anaerobic condition had been discovered. In addition to nitrite, iron trivalent, sulfate, manganese and electrons from electrode might be potential electron acceptors for ammonium oxidation, which can be coupled to traditional BNR process for wastewater treatment. In this paper, the pathway and mechanism for ammonium oxidation with various electron acceptors under anaerobic condition is studied comprehensively, and the research progress of potentially functional microbes is summarized. The potential application of various electron acceptors for ammonium oxidation in wastewater is addressed, and the N2O emission during nitrogen removal is also discussed, which was important greenhouse gas for global climate change. The problems remained unclear for ammonium oxidation by multi-electron acceptors and potential interactions are also discussed in this review.

Corrigendum: Assessing heterogeneity of patient and health system delay among TB in a population with internal migrants in China.

[This corrects the article DOI: 10.3389/fpubh.2024.1354515.].

Microfluidic device featuring micro-constrained channels for multi-parametric assessment of cellular biomechanics and high-precision mechanical phenotyping of gastric cells.

BACKGROUND: Cellular biomechanics plays a significant role in the regulation of cellular physiological and pathological processes. In recent years, multiple methods have been developed to evaluate cellular biomechanics, such as atomic force microscopy (AFM), micropipette aspiration, and magnetic tweezers. However, most of these methods only focus on a single parameter and cannot automate the process at a high-efficiency level. A novel microfluidic method is necessary to achieve the simultaneous multi-parametric measurement of cellular biomechanics and high-precision cellular mechanical phenotyping at high throughput. RESULTS: To tackle the issue concerning the low-throughput and cellular single-parameter evaluation, we designed and fabricated a microfluidic chip featuring multiple micro-constrained channels structure, providing a simultaneous multi-parametric assessment of cellular biomechanics, including elastic modulus, recovery capability, and deformability. We compared the biomechanical properties of normal human gastric mucosal epithelial cells (GES-1) and human gastric cancer cells (AGS and MKN-45) by the chip. Results demonstrated that the elastic modulus of GES-1, AGS, and MKN-45 cells decreased sequentially, which was the opposite of their invasiveness and metastasis potential, suggesting the inverse correlation between cellular elastic modulus and malignancy. Meanwhile, the recovery capability and deformability of GES-1, AGS, and MKN-45 cells increased sequentially, demonstrating the positive correlation between cellular deformability and malignancy. Furthermore, multiple parameters were used to distinguish gastric cancer cells from normal gastric cells via machine learning. An accuracy of over 94.8% for identifying gastric cancer cells was achieved. SIGNIFICANCE: This study provides a deep insight into the biophysical mechanism of gastric cancer metastasis at the single-cell level and possesses great potential to function as a valuable tool for single-cell analysis, thereby facilitating high-precision and high-throughput discrimination of cellular phenotypes that are not easily discernible through single-marker analysis.

Assessing heterogeneity of patient and health system delay among TB in a population with internal migrants in China.

Backgrounds: The diagnostic delay of tuberculosis (TB) contributes to further transmission and impedes the implementation of the End TB Strategy. Therefore, we aimed to describe the characteristics of patient delay, health system delay, and total delay among TB patients in Shanghai, identify areas at high risk for delay, and explore the potential factors of long delay at individual and spatial levels. Method: The study included TB patients among migrants and residents in Shanghai between January 2010 and December 2018. Patient and health system delays exceeding 14 days and total delays exceeding 28 days were defined as long delays. Time trends of long delays were evaluated by Joinpoint regression. Multivariable logistic regression analysis was employed to analyze influencing factors of long delays. Spatial analysis of delays was conducted using ArcGIS, and the hierarchical Bayesian spatial model was utilized to explore associated spatial factors. Results: Overall, 61,050 TB patients were notified during the study period. Median patient, health system, and total delays were 12 days (IQR: 3-26), 9 days (IQR: 4-18), and 27 days (IQR: 15-43), respectively. Migrants, females, older adults, symptomatic visits to TB-designated facilities, and pathogen-positive were associated with longer patient delays, while pathogen-negative, active case findings and symptomatic visits to non-TB-designated facilities were associated with long health system delays (LHD). Spatial analysis revealed Chongming Island was a hotspot for patient delay, while western areas of Shanghai, with a high proportion of internal migrants and industrial parks, were at high risk for LHD. The application of rapid molecular diagnostic methods was associated with reduced health system delays. Conclusion: Despite a relatively shorter diagnostic delay of TB than in the other regions in China, there was vital social-demographic and spatial heterogeneity in the occurrence of long delays in Shanghai. While the active case finding and rapid molecular diagnosis reduced the delay, novel targeted interventions are still required to address the challenges of TB diagnosis among both migrants and residents in this urban setting.

Efficient spiking neural network design via neural architecture search.

Spiking neural networks (SNNs) are brain-inspired models that utilize discrete and sparse spikes to transmit information, thus having the property of energy efficiency. Recent advances in learning algorithms have greatly improved SNN performance due to the automation of feature engineering. While the choice of neural architecture plays a significant role in deep learning, the current SNN architectures are mainly designed manually, which is a time-consuming and error-prone process. In this paper, we propose a spiking neural architecture search (NAS) method that can automatically find efficient SNNs. To tackle the challenge of long search time faced by SNNs when utilizing NAS, the proposed NAS encodes candidate architectures in a branchless spiking supernet which significantly reduces the computation requirements in the search process. Considering that real-world tasks prefer efficient networks with optimal accuracy under a limited computational budget, we propose a Synaptic Operation (SynOps)-aware optimization to automatically find the computationally efficient subspace of the supernet. Experimental results show that, in less search time, our proposed NAS can find SNNs with higher accuracy and lower computational cost than state-of-the-art SNNs. We also conduct experiments to validate the search process and the trade-off between accuracy and computational cost.

Investigating adaptive sport participation for adults aged 50 years or older with spinal cord injury or disease: A descriptive cross-sectional survey.

CONTEXT: Spinal cord injury or disease (SCI/D) can lead to health challenges that are exacerbated with aging. Adaptive sport is understood to provide health benefits for the SCI/D population. Prior literature investigating adaptive sport in this population pertains to adults with SCI/D who are <50 years of age. However, most Canadians with SCI/D are >50 years of age. OBJECTIVES: This study aimed to: (1) Compare demographics of those who do and do not participate in adaptive sport; (2) Describe the characteristics of adaptive sport that adults aged ≥50 years with SCI/D participate in; and (3) Identify barriers and facilitators to adaptive sport participation in this age group. METHODS: This descriptive, cross-sectional survey was carried out using an online survey. Analytical statistics were used to address objective one, while descriptive statistics were employed for objectives two and three. PARTICIPANTS: Responses from 72 adults aged ≥50 years, residing in Canada, living with a SCI/D for >6 months were included in the analysis. RESULTS: Findings revealed that adaptive sport participants aged ≥50 years with SCI/D were more likely to identify as men, be younger individuals (50-59 years), and report greater satisfaction with physical health (P < 0.05). Adaptive sport participants most commonly played individual sports at the recreational level. Common barriers pertained to physical capacity, travel, and COVID-19; common facilitators included social support, desire to improve health, and having friends/peers who also participate. CONCLUSION: Future research should investigate strategies to enhance facilitators and mitigate barriers to adaptive sport participation in order to improve access.

Genetic determinants of IgG antibody response to COVID-19 vaccination.

Human humoral immune responses to SARS-CoV-2 vaccines exhibit substantial inter-individual variability and have been linked to vaccine efficacy. To elucidate the underlying mechanism behind this variability, we conducted a genome-wide association study (GWAS) on the anti-spike IgG serostatus of UK Biobank participants who were previously uninfected by SARS-CoV-2 and had received either the first dose (n = 54,066) or the second dose (n = 46,232) of COVID-19 vaccines. Our analysis revealed significant genome-wide associations between the IgG antibody serostatus following the initial vaccine and human leukocyte antigen (HLA) class II alleles. Specifically, the HLA-DRB1∗13:02 allele (MAF = 4.0%, OR = 0.75, p = 2.34e-16) demonstrated the most statistically significant protective effect against IgG seronegativity. This protective effect was driven by an alteration from arginine (Arg) to glutamic acid (Glu) at position 71 on HLA-DRß1 (p = 1.88e-25), leading to a change in the electrostatic potential of pocket 4 of the peptide binding groove. Notably, the impact of HLA alleles on IgG responses was cell type specific, and we observed a shared genetic predisposition between IgG status and susceptibility/severity of COVID-19. These results were replicated within independent cohorts where IgG serostatus was assayed by two different antibody serology tests. Our findings provide insights into the biological mechanism underlying individual variation in responses to COVID-19 vaccines and highlight the need to consider the influence of constitutive genetics when designing vaccination strategies for optimizing protection and control of infectious disease across diverse populations.

DBC1 maintains skeletal muscle integrity by enhancing myogenesis and preventing myofibre wasting.

BACKGROUND: Skeletal muscle atrophy, particularly ageing-related muscular atrophy such as sarcopenia, is a significant health concern. Despite its prevalence, the underlying mechanisms remain poorly understood, and specific approved medications are currently unavailable. Deleted in breast cancer 1 (DBC1) is a well-known regulator of senescence, metabolism or apoptosis. Recent reports suggest that DBC1 may also potentially regulate muscle function, as mice lacking DBC1 exhibit weakness and limpness. However, the function of DBC1 in skeletal muscle and its associated molecular mechanisms remain unknown, thus prompting the focus of this study. METHODS: Tibialis anterior (TA) muscle-specific DBC1 knockdown C57BL/6J male mice were generated through a single injection of 2.00 E + 11 vg of adeno-associated virus 9 delivering single-guide RNA for DBC1. Grip strength and endurance were assessed 2 months later, followed by skeletal muscle harvest. Muscle atrophy model was generated by cast immobilization of the mouse hindlimb for 2 weeks. Molecular markers of atrophy were probed in muscles upon termination. Cardiotoxin (CTX) was injected in TA muscles of DBC1 knockdown mice, and muscle regeneration was assessed by immunohistochemistry, quantitative PCR and western blotting. DBC1 knockdown C2C12 cells and myotubes were investigated using immunofluorescence staining, Seahorse, immunohistology, fluorescence-activated cell sorting and RNA-sequencing analyses. RESULTS: DBC1 knockdown in skeletal muscle of young mice led to signatures of muscle atrophy, including a 28% reduction in muscle grip force (P = 0.023), a 54.4% reduction in running distance (P = 0.002), a 14.3% reduction in muscle mass (P = 0.007) and significantly smaller myofibre cross-sectional areas (P < 0.0001). DBC1 levels decrease in age-related or limb immobilization-induced atrophic mouse muscles and overexpress DBC1-attenuated atrophic phenotypes in these mice. Muscle regeneration was hampered in mice with CTX-induced muscle injury by DBC1 knockdown, as evidenced by reductions in myofibre cross-sectional areas of regenerating myofibres with centralized nuclei (P < 0.0001), percentages of MyoG+ nuclei (P < 0.0001) and fusion index (P < 0.0001). DBC1 transcriptionally regulated mouse double minute 2 (MDM2), which mediated ubiquitination and degradation of forkhead box O3 (FOXO3). Increased FOXO3 proteins hampered myogenesis in DBC1 knockdown satellite cells by compromising around 50% of mitochondrial functions (P < 0.001) and exacerbated atrophy in DBC1 knockdown myofibres by activating the ubiquitin-proteasome and autophagy-lysosome pathways. CONCLUSIONS: DBC1 is essential in maintaining skeletal muscle integrity by protecting against myofibres wasting and enhancing muscle regeneration via FOXO3. This research highlights the significance of DBC1 for healthy skeletal muscle function and its connection to muscular atrophy.

Immobilization of laccase on magnetic mesoporous silica as a recoverable biocatalyst for the efficient degradation of benzo[a]pyrene.

Laccase is an efficient green biocatalyst, widely used for the degradation of various organic pollutants. However, free laccase is unstable and difficult to recover, which limits its practical application. In this study, a multilayer core-shell magnetic mesoporous silica (Fe3O4@d-SiO2@p-SiO2) microsphere with high specific surface area (275 m2 g-1) was fabricated for immobilization of laccase. The unique structure of Fe3O4@d-SiO2@p-SiO2 enabled the successful immobilization of laccase. Under the optimal immobilization conditions of laccase concentration of 1.5 mg mL-1, immobilization time of 6 h, immobilization pH of 6, the loading capacity of laccase was up to 567 mg g-1. Compared with free laccase, immobilized laccase exhibited remarkable pH stability, thermal stability and storage stability. Moreover, the immobilized laccase was easy to achieve magnetic recovery and possessed excellent reusability, with its activity remaining 58.2% after 10 consecutive reuses. More importantly, immobilized laccase had good degradation performance for benzo[a]pyrene (BaP), which can achieve rapid and efficient degradation of low concentration BaP over a wide range of pH and temperature. The removal efficiency of BaP was up to 99.0% within 1 h, and still exceeded 35.0% after 5 cycles. The removal of BaP by immobilized laccase was achieved through both adsorption and degradation. The degradation products and possible degradation pathways were determined by GC-MS analysis. This study indicated that Fe3O4@d-SiO2@p-SiO2 could effectively enhance the stability and biocatalytic activity of laccase, which is expected to provide a new clean biotechnology for the remediation of BaP contaminated sites.

LINC01140 Hinders the Development of Breast Cancer Through Targeting miR-200b-3p to Downregulate DMD.

Long non-coding RNAs (lncRNAs) are frequently reported to be involved in breast cancer (BC) oncogenicity. The goal of this study was to probe lncRNA LINC01140's role and action mechanism in BC. Relative LINC01140, miR-200b-3p, and dystrophin (DMD) levels were determined using quantitative real-time polymerase chain reaction (qRT-PCR). DMD protein levels in BC cells were quantified using Western blotting, and the targeting relationships were validated by luciferase reporter assays and RNA immunoprecipitation experiments. The proliferative potential of the cells was evaluated using CCK-8 and colony formation tests, while the migratory and invasive abilities of the cells were assessed using scratch and transwell assays. Apoptosis was assessed by flow cytometry. Nude mouse models have been established to allow the examination of tumor growth in vivo. Pronounced downregulation of LINC01140 and DMD, as well as upregulation of miR-200b-3p, was observed in BC. LINC01140 binds directly to miR-200b-3p to downregulate DMD expression. Ectopic LINC01140 expression not only limited tumor growth in vivo but also diminished the proliferation, migration, and invasion abilities of BC cells in vitro, however, it induced apoptosis in BC cells. Elevated miR-200b-3p expression stimulated the tumorigenic potential of BC cells and attenuated the suppressive effect of LINC01140 or DMD overexpression on BC cell malignancy, whereas DMD overexpression restricted the tumorigenic potential of BC cells. Overall, LINC01140 prevents BC development via the miR-200b-3p-DMD axis. These findings support the latent potential and usefulness of the LINC01140-miR-200b-3p-DMD network as a target for BC therapy.

A Novel Compute-and-Forward Relaying Method for Multi-Antenna Wireless Relay Networks.

Compute-and-Forward (CoF) is an innovative physical layer network coding strategy, designed to enable receivers in wireless communications to effectively utilize interference. The key idea of CoF is to implement integer combinations based on the codewords from multiple transmitters, rather than decoding individual source codewords. Although CoF is widely used in wireless relay networks, there are still some problems to be solved, such as rank failure, single antenna reception, and the shortest vector problem. In this paper, we introduce a successive extended CoF (SECoF) as a pioneering solution tailored for multi-source, multi-relay, and multi-antenna wireless relay networks. First, we analyze the traditional CoF, and design a SECoF method combining the concepts of matrix projection and successive interference cancellation, which overcomes the problem of CoF rate tending to zero and rank failure and improves the network performance. Secondly, we obtain an approximate solution to the integer-value coefficient vectors by using the LLL lattice-based resolution algorithm. In addition, we deduce the corresponding concise formulas of SECoF. Simulation results show that the SECoF has strong robustness and the approaches outperform the state-of-the-art methods in terms of computation rate, rank failure probability, and outage probability.

First Report of Lasiodiplodia pseudotheobromae causing Postharvest Decay of Strawberries in Florida.

Postharvest decay of strawberry (Fragaria × ananassa Duch.) is a major factor causing fruit losses. Strawberries were obtained from various harvests at cooling facilities located in Dover and Plant City, FL during the 2018-19 and 2019-20 seasons. After the fruits were incubated at 22ºC for up to 5 days (d) to promote disease development, Lasiodiplodia decay was observed at up to 3% from some harvests, exhibiting gray mycelia on small lesions that gradually covered the whole fruit. The fungus was isolated onto potato dextrose agar (PDA). Five isolates (SBD18-14, SBD18-277, SBD18-279, SBD19-02 and SBD19-57) were characterized. Fungal mycelia were initially grayish white and then gradually changed to gray to dark gray on PDA at 25oC, and later produced black pigments (Fig. S1). Pycnidia were observed from inoculated strawberries at 14 d. Isolates shared similar conidia morphology: aseptate, hyaline, ellipsoid to ovoid, measuring L × W: 24.0-34.0 (28.3) × 13.0-16.0 (14.3) µm (n =100). Mature conidia were brown, one septate, measuring L × W: 25.0-33.0 (28.8) × 13.0-16.0 (14.5) µm (n =100). The isolates were identified as Lasiodiplodia spp. morphologically (Alves et al. 2008). DNA was extracted from fungal mycelia using an OmniPrep DNA extraction kit, and PCR amplification of ITS and EF1-α genes was performed following the conditions described by White et al. (1990) with some modifications using primers ITS1F-F/ITS4-R (Gardes and Bruns, 1993; White et al., 1990) and EF1-668-F/EF1-1251-R (Alves et al., 2008), respectively. The BLASTn in GenBank showed that the sequences obtained had 99.61 to 100% homology with those of ITS (EF622077) and EF1-α (EF622057) from L. pseudotheobromae CBS116459 (an ex-type strain) (Alves et al., 2008). Sequences of the isolates have been deposited in GenBank with accessions OP326017 to OP326021 for ITS, and OP356202 to OP356206 for EF1-α. Phylogenetic analysis showed that these isolates clustered in the same clade (bootstrap value at 64) with L. pseudotheobromae (Fig. S2). Two fungal inoculum types (mycelia and conidia), two fruit inoculation methods (injury and non-injury) and five fungal isolates were used for pathogenicity tests. Fungal mycelia (2-day-old) on PDA plug (5 mm) or 10 µL of conidial suspension (106 spores/mL) was placed onto each injury (1 x 1 mm in size) or a non-injury area on the surfaces of five strawberry fruits (cv. Florida Brilliance). PDA plug alone or water drops placed on injury or non-injury areas on fruits served as respective controls. Inoculated and control fruits were incubated in a covered plastic container with 100% RH at 22ºC. The experiment was repeated twice. Decay initially appeared as soft and lightly discolored tissue at inoculation areas 2 d post-inoculation (dpi) that extended quickly thereafter. Brown to dark lesions on both injury- and non-injury fruits inoculated with conidia or mycelia were observed at 3 dpi. Decay and gray mycelia gradually developed over the whole fruit at 6 dpi, and pycnidia were observed after 14 dpi (Fig. S1). Disease incidence of 100% was observed on all tests. Control fruits did not develop decay. The results indicate that these isolates are pathogenic to strawberries and infect fruit via both non-injured and injured fruit surfaces. The inoculated fungal isolates were re-isolated, thus, fulfilling Koch's postulates. L. theobromae, Neofusicoccum parvum/N. ribis species complex causing strawberry fruit rot in Florida fields was reported (Oliveira et al., 2019), but not L. pseudotheobromae. To our knowledge, this is the first report of postharvest decay caused by L. pseudotheobromae A.J.L. Phillips, A. Alves & Crous on strawberries in Florida and in the USA, and it should be considered in strawberry disease management.

An autocatalytic multicomponent DNAzyme nanomachine for tumor-specific photothermal therapy sensitization in pancreatic cancer.

Multicomponent deoxyribozymes (MNAzymes) have great potential in gene therapy, but their ability to recognize disease tissue and further achieve synergistic gene regulation has rarely been studied. Herein, Arginylglycylaspartic acid (RGD)-modified Distearyl acylphosphatidyl ethanolamine (DSPE)-polyethylene glycol (PEG) (DSPE-PEG-RGD) micelle is prepared with a DSPE hydrophobic core to load the photothermal therapy (PTT) dye IR780 and the calcium efflux pump inhibitor curcumin. Then, the MNAzyme is distributed into the hydrophilic PEG layer and sealed with calcium phosphate through biomineralization. Moreover, RGD is attached to the outer tail of PEG for tumor targeting. The constructed nanomachine can release MNAzyme and the cofactor Ca2+ under acidic conditions and self-assemble into an active mode to cleave heat shock protein (HSP) mRNA by consuming the oncogene miRNA-21. Silencing miRNA-21 enhances the expression of the tumor suppressor gene PTEN, leading to PTT sensitization. Meanwhile, curcumin maintains high intracellular Ca2+ to further suppress HSP-chaperone ATP by disrupting mitochondrial Ca2+ homeostasis. Therefore, pancreatic cancer is triple-sensitized to IR780-mediated PTT. The in vitro and in vivo results show that the MNAzyme-based nanomachine can strongly regulate HSP and PTEN expression and lead to significant pancreatic tumor inhibition under laser irradiation.

In Situ Decoration of Bi2S3 Nanosheets on Zinc Oxide/Cellulose Acetate Composite Films for Photodegradation of Dyes under Visible Light Irradiation.

A novel Bi2S3-zinc oxide/cellulose acetate composite film was prepared through a blending-wet phase conversion and in situ precipitate method. The results revealed that the incorporation of Bi2S3 in the film increased the cavity density and uniformity, which provided additional space for the growth of active species and improved the interaction between dye pollutants and active sites. Zinc oxide acted as a mediator to facilitate the separation of electron-hole pairs effectively preventing their recombination, thus reducing the photo-corrosion of Bi2S3. As a result, the Bi2S3-ZnO/CA composite film exhibited favorable photocatalytic activity in the degradation of various dyes. Additionally, the composite film displayed effortless separation and recovery without the need for centrifugation or filtration, while maintaining its exceptional catalytic performance even after undergoing various processes.

Structural analysis of the ferric-binding protein KfuA from Klebsiella pneumoniae.

Iron acquisition is an essential process of cell physiology for biological systems. In Klebsiella pneumoniae, the siderophore and ferric-acquisition ABC (ATP-Binding-Cassette) transporter KfuABC is utilized for iron uptake. Initial recognition of the various ferric sources in periplasm and transportation across the cytoplasmic membrane is performed by the substrate-binding protein (SBP) KfuA. Here we report the 2.0 Å resolution crystal structure of KfuA from K. pneumoniae, which crystallizes in the space group P1211 with a single monomer in the asymmetric unit. A bound metal ion reveals the residues required for binding ferric ions. Binding analysis shows that ferric iron and the iron-mimicking gallium bind with high affinity to KfuA. Growth curves show that gallium inhibits growth of K. pneumoniae whereas ferric iron enhances it. This work suggests a mechanism whereby gallium effectively competes with ferric iron, disrupting iron-dependent biological functions via binding to KfuA and leading to heightened antimicrobial efficacy. Significantly, humans lack equivalent ABC transporters like SBP KfuA, underscoring the potential of KfuA as an attractive target for therapeutic intervention.

Tunable thermoplastic elastomer gels derived from controlled-distribution triblock copolymers with crystallizable endblocks.

Thermoplastic elastomers (TPEs), a commercially important category of triblock copolymers, are employed alone or upon physical modification with a midblock-selective oil (to form TPE gels, TPEGs) in a broad range of contemporary technologies. While most copolymers in this class of self-networking macromolecules possess glassy polystyrene endblocks and a rubbery polydiene or polyolefin midblock, we investigate TPEGs fabricated from a novel controlled-distribution copolymer with crystallizable polyolefin endblocks and a random-copolymer midblock. According to both electron microscopy and small-angle scattering, the morphologies of these TPEGs remain largely invariant up to 40 wt% oil and then transform considerably at higher oil levels. Although reductions in endblock melting point and crystallinity measured by thermal calorimetry accompany increasing oil content, mechanical properties such as the uniaxial strain at break and fracture toughness improve in some cases by over 50% between 5 and 40 wt% oil. In fact, the strain at break can reach 2500% within this range, thereby confirming that (i) the structure-property relationships of these unique TPEGs are highly composition-tunable and (ii) these TPEGs, stabilized by crystallizable endblocks, provide an attractive alternative for ultrasoft and stretchy recyclable materials.

DNA Nanoflower Eye Drops with Antibiotic-Resistant Gene Regulation Ability for MRSA Keratitis Target Treatment.

Methicillin-resistant Staphylococcus aureus (MRSA) biofilm-associated bacterial keratitis is highly intractable, with strong resistance to ß-lactam antibiotics. Inhibiting the MRSA resistance gene mecR1 to downregulate penicillin-binding protein PBP2a has been implicated in the sensitization of ß-lactam antibiotics to MRSA. However, oligonucleotide gene regulators struggle to penetrate dense biofilms, let alone achieve efficient gene regulation inside bacteria cells. Herein, an eye-drop system capable of penetrating biofilms and targeting bacteria for chemo-gene therapy in MRSA-caused bacterial keratitis is developed. This system employed rolling circle amplification to prepare DNA nanoflowers (DNFs) encoding MRSA-specific aptamers and mecR1 deoxyribozymes (DNAzymes). Subsequently, ß-lactam antibiotic ampicillin (Amp) and zinc oxide (ZnO) nanoparticles are sequentially loaded into the DNFs (ZnO/Amp@DNFs). Upon application, ZnO on the surface of the nanosystem disrupts the dense structure of biofilm and fully exposes free bacteria. Later, bearing encoded aptamer, the nanoflower system is intensively endocytosed by bacteria, and releases DNAzyme under acidic conditions to cleave the mecR1 gene for PBP2a down-regulation, and ampicillin for efficient MRSA elimination. In vivo tests showed that the system effectively cleared bacterial and biofilm in the cornea, suppressed proinflammatory cytokines interleukin 1ß ï¼ˆIL-1ß） and tumor neocrosis factor-alpha （TNF-α）, and is safe for corneal epithelial cells. Overall, this design offers a promising approach for treating MRSA-induced keratitis.