Improved sensitivity analysis method and decision error discussion for limiting short-circuit current of power grid

This study mainly focuses on the method of limiting short-circuit current of a power grid by partial transmission switching. The restrictive effect of short-circuit current and the integrality of the power grid should be considered before the choosing the transmission lines. By analysing the relationship between transmission switching and self-impedance of bus with increasing short-circuit current magnitude, a sensitivity matrix can be derived. Based on sensitivity analysis, a set of the least transmission switching is chosen, which can limit short-circuit current to the maximum. This study improves the method of transmission lines selection by sensitivity analysis. The improved sensitivity analysis method directly selects a set of transmission switching lines by the maximum value of weighted sensitivity coefficient instead of selecting lines one by one. It requires less calculation and has a high-computation speed, but there are engineering errors. This work also studies the error influencing the decision of lines selection in different power grid scales. The effectiveness of the improved sensitivity analysis method is verified by several case studies. The cases of different power system scales are utilised for discussing the impact of error on decision of lines selection and for drawing the scope of the improved sensitivity analysis method

A Targeted and Stable Polymeric Nanoformulation Enhances Systemic Delivery of mRNA to Tumors

The high vulnerability of mRNA necessitates the manufacture of delivery vehicles to afford adequate protection in the biological milieu. Here, mRNA was complexed with a mixture of cRGD-poly(ethylene glycol) (PEG)-polylysine (PLys) (thiol) and poly(N-isopropylacrylamide) (PNIPAM)-PLys(thiol). The ionic complex core consisting of opposite-charged PLys and mRNA was crosslinked though redox-responsive disulfide linkage, thereby avoiding structural disassembly for exposure of mRNA to harsh biological environments. Furthermore, PNIPAM contributed to prolonged survival in systemic circulation by presenting a spatial barrier in impeding accessibility of nucleases, e.g., RNase, due to the thermo-responsive hydrophilic-hydrophobic transition behavior upon incubation at physiological temperature enabling translocation of PNIPAM from shell to intermediate barrier. Ultimately, the cRGD ligand attached to the formulation demonstrated improved tumor accumulation and potent gene expression, as manifested by virtue of facilitated cellular uptake and intracellular trafficking. These results indicate promise for the utility of mRNA as a therapeutic tool for disease treatment

Nano‐omics: Frontier fields of fusion of nanotechnology

Abstract Nanotechnology, an emerging force, has infiltrated diverse domains like biomedical, materials, and environmental sciences. Nano‐omics, an emerging fusion, combines nanotechnology with omics, boasting amplified sensitivity and resolution. This review introduces nanotechnology basics, surveys its recent strides in nano‐omics, deliberates present challenges, and envisions future growth

Enhanced Precision Therapy of Multiple Myeloma Through Engineered Biomimetic Nanoparticles with Dual Targeting

Multiple myeloma (MM) is the second most prevalent hematological malignancy. Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy. This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy, which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes, termed T-PB@M. The results from our investigations highlight the considerable bone affinity of T-PB@M, both in vitro and in vivo. Additionally, this material demonstrated a capability for drug release triggered by low pH conditions. Moreover, T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose) polymerase 1 (PARP1)–Caspase-3–B-cell lymphoma-2 (Bcl-2) pathway in MM cells. Notably, T-PB@M preferentially targeted bone-involved sites, thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice. Therefore, this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM

Prenatal famine exposure, adulthood obesity patterns and risk of type 2 diabetes

Abstract Background: Prenatal exposure to famine and adulthood obesity have been independently related to the risk of type 2 diabetes; however, little is known about the joint effects of these risk factors at different stages of life on adulthood diabetes risk. Methods: The analysis included 88 830 participants of the China Kadoorie Biobank, who were born around the time of the Chinese Great Famine and without diabetes, cardiovascular diseases, or cancer at baseline. We defined famine exposure subgroups as nonexposed (born between 1 October 1962 and 30 September 964), fetal-exposed (born between 1 October 1959 and 30 September 1961) and early-childhood exposed (born between 1 October 1956 and 30 September 1958). General obesity was assessed by body mass index (BMI: overweight ≥ 24.0, obesity ≥ 28.0) and abdominal obesity assessed by waist-to-hip ratio (WHR, men/women: moderate ≥ 0.90/0.85, high ≥ 0.95/0.90). Results: During a median 7.3 years (642 552 person-years) of follow-up, we identified 1372 incident cases of type 2 diabetes. Compared with nonexposed and early-childhood exposed participants combined as a single comparison group, fetal-exposed participants showed an increased risk of diabetes in adulthood [hazard ratio (HR) = 1.25; 95% confidence interval (CI): 1.07–1.45]. The association between general obesity and diabetes was consistent across subgroups according to famine exposure (P for interaction > 0.05). A stronger association between abdominal obesity and diabetes was observed in the fetal-exposed subgroup than in other subgroups (P for interaction = 0.025 in the whole population). This interaction was more obvious in women (P = 0.013) but not in men (P = 0.699). Compared with normal-BMI and -WHR participants, those with both general (BMI ≥ 24.0) and abdominal (WHR ≥ 0.90/0.85) obesity in adulthood had 5.32 (95% CI: 3.81–7.43)-, 3.13 (2.48–3.94)- and 4.43 (3.45–5.68)-fold higher risks if these were carried during, before and after times of famine, respectively. Conclusions: Coexistence of prenatal experience of undernutrition and abdominal obesity in adulthood was associated with a higher risk of type 2 diabetes

Whole Transcriptome Analysis Identifies Platycodin D-Mediated RNA Regulatory Network in Non–Small-Cell Lung Cancer

Non–small-cell lung cancer (NSCLC) is one of the most fatal malignant tumors harmful to human health. Previous studies report that Platycodin D (PD) exhibits anti-tumor effects in multiple human cancers, including NSCLC, but the underlying mechanisms are largely unknown. Accumulating evidence indicates that non-coding RNAs (ncRNAs) participate in NSCLC disease progression, but the link between PD and the ncRNAs in NSCLC is poorly elucidated. Here, we used whole transcriptome sequencing to systematically investigate the RNAs-associated regulatory network in the PD treating NSCLC cell lines. A total of 942 significantly dysregulated RNAs were obtained. Among those, five circRNAs and six IncRNAs were rigorously selected via database and in vitro validation. In addition, the functional enrichment study of differentially expressed mRNAs, single nucleotide polymorphisms (SNPs) within PD-related mRNA structures, and the interaction between PD and mRNA-related proteins were analyzed through gene set enrichment analysis (GSEA), structural variant analysis, and molecular docking, respectively. With further in vitro validation, the results show that PD inhibits cell proliferation, arrests the cell cycle, and induces cell apoptosis through targeting BCL2-related proteins. We hope these data can provide a full concept of PD-related molecular changes, leading to a new treatment for NSCLC

Polymeric Nanostructure Compiled with Multifunctional Components To Exert Tumor-Targeted Delivery of Antiangiogenic Gene for Tumor Growth Suppression

Nucleic acid-based therapy has emerged as a revolutionary methodology for treatment of the diseases related to protein dysfunction; however, lack of systemically applicable synthetic delivery systems limits its current usage in local applications, particularly for DNA-based therapy with regard to the poor bioavailability in the systemic administrations. To overcome this obstacle, we compiled multiple chemistry-based strategies into the manufacture of the gene delivery formulations to pursue improved tolerability of DNA to the enzymatic degradation in the biological milieu and prolonged retention in the systemic circulation. Here, we constructed a distinctive multilayered functional architecture: plasmid DNA (pDNA) was electrostatically complexed with cationic poly­(lysine) (polyplex) as the interior pDNA reservoir, which was further cross-linked by redox-responsive disulfide cross-linking to minimize the occurrence of polyplex disassembly through exchange reaction with the biological charged components. Still, the pDNA reservoir was spatially protected by a sequential thermoresponsive poly­(<i>N</i>-isopropylacrylamide) palisade as the intermediate barrier and a biocompatible hydrophilic poly­(ethylene glycol) (PEG) shell with the aim of preventing the accessibility of the biological species, particularly the nuclease degradation to the pDNA payload. Subsequent investigations validated the utilities of these strategies in accomplishing prolonged blood retention. In an attempt to apply this method for tumor therapy, ligand cyclic (Arg-Gly-Asp) peptide was attached at the distal end of PEG, validating prompted tumor-targeted delivery and gene expression of the loaded antiangiogenic gene at the targeted tumor cells and accordingly exerting antiangiogenesis of the tumors for abrogation of tumor growth. Together with its excellent safe profile, the proposed formulation suggests potential utility as a practical gene delivery system for treatment of intractable diseases

Silver-Nanoparticle-Embedded Porous Silicon Disks Enabled SERS Signal Amplification for Selective Glutathione Detection

As the major redox couple and nonprotein thiol source in human tissues, the level of glutathione (GSH) has been a concern for its relation with many diseases. However, the similar physical and chemical properties of interference molecules such as cysteine (Cys) and homocysteine (Hcy) make discriminative detection of GSH in complex biological fluids challenging. Here we report a novel surface-enhanced Raman scattering (SERS) platform, based on silver-nanoparticle-embedded porous silicon disks (PSDs/Ag) substrates for highly sensitive and selective detection of GSH in biofluids. Silver nanoparticles (AgNPs) were reductively synthesized and aggregated directly into pores of PSDs, achieving a SERS enhancement factor (EF) up to 2.59 × 10⁷. Ellman’s reagent 5,5′-ditho-bis (2-nitrobenzoic acid) (DTNB) was selected as the Raman reactive reporting agent, and the GSH quantification was determined using enzymatic recycling method, and allowed the detection limit of GSH to be down to 74.9 nM using a portable Raman spectrometer. Moreover, the significantly overwhelmed enhancement ratio of GSH over other substances enables the discrimination of GSH detection in complex biofluids