Multidrug resistance (MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence. Therefore, combatting MDR is an important issue. Autophagy, a ...self-degradative system, universally arises during the treatment of sensitive and MDR cancer. Autophagy can be a double-edged sword for MDR tumors: it participates in the development of MDR and protects cancer cells from chemotherapeutics but can also kill MDR cancer cells in which apoptosis pathways are inactive. Autophagy induced by anticancer drugs could also activate apoptosis signaling pathways in MDR cells, facilitating MDR reversal. Therefore, research on the regulation of autophagy to combat MDR is expanding and is becoming increasingly important. We summarize advanced studies of autophagy in MDR tumors, including the variable role of autophagy in MDR cancer cells.
As electronic device feature sizes scale‐down, the power consumed due to onchip communications as compared to computations will increase dramatically; likewise, the available bandwidth per ...computational operation will continue to decrease. Integrated photonics can offer savings in power and potential increase in bandwidth for onchip networks. Classical diffraction‐limited photonics currently utilized in photonic integrated circuits (PIC) is characterized by bulky and inefficient devices compared to their electronic counterparts due to weak light–matter interactions (LMI). Performance critical for the PIC is electro‐optic modulators (EOM), whose performances depend inherently on enhancing LMIs. Current EOMs based on diffraction‐limited optical modes often deploy ring resonators and are consequently bulky, photon‐lifetime modulation limited, and power inefficient due to large electrical capacitances and thermal tuning requirements. In contrast, wavelength‐scale EOMs are potentially able to surpass fundamental restrictions set by classical (i.e. diffraction‐limited) devices via (a) high‐index modulating materials, (b) nonresonant field and density‐of‐states enhancements such as found in metal optics, and (c) synergistic onchip integration schemes. This manuscript discusses challenges, opportunities, and early demonstrations of nanophotonic EOMs attempting to address this LMI challenge, and early benchmarks suggest that nanophotonic building blocks allow for densely integrated high‐performance photonic integrated circuits.
The performances of electro‐optic modulators (EOM) is determined by the interaction strength between light and matter. Here, EOMs based on sub‐diffraction‐limited optical modes are summarized and discussed. These devices show performance metrics that are able to surpass classical device limits through (a) optical field enhancements, (b) low‐Q resonators and (c) synergistic integration schemes including emerging materials for strong index modulation.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Neuroimaging‐driven brain age estimation has become popular in measuring brain aging and identifying neurodegenerations. However, the single estimated brain age (gap) compromises regional variations ...of brain aging, losing spatial specificity across diseases which is valuable for early screening. In this study, we combined brain age modeling with Shapley Additive Explanations to measure brain aging as a feature contribution vector underlying spatial pathological aging mechanism. Specifically, we regressed age with volumetric brain features using machine learning to construct the brain age model, and model‐agnostic Shapley values were calculated to attribute regional brain aging for each subject's age estimation, forming the brain age vector. Spatial specificity of the brain age vector was evaluated among groups of normal aging, prodromal Parkinson disease (PD), stable mild cognitive impairment (sMCI), and progressive mild cognitive impairment (pMCI). Machine learning methods were adopted to examine the discriminability of the brain age vector in early disease screening, compared with the other two brain aging metrics (single brain age gap, regional brain age gaps) and brain volumes. Results showed that the proposed brain age vector accurately reflected disorder‐specific abnormal aging patterns related to the medial temporal and the striatum for prodromal AD (sMCI vs. pMCI) and PD (healthy controls HC vs. prodromal PD), respectively, and demonstrated outstanding performance in early disease screening, with area under the curves of 83.39% and 72.28% in detecting pMCI and prodromal PD, respectively. In conclusion, the proposed brain age vector effectively improves spatial specificity of brain aging measurement and enables individual screening of neurodegenerative diseases.
We combined brain age modeling with SHAP feature attribution to measure brain aging as a feature contribution vector underlying spatial pathological aging mechanism. The proposed brain age vector accurately revealed disorder‐specific spatial abnormal aging patterns, and enhanced individual early screening of neurodegenerative diseases.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
In this study, the refinement of two microstructures was controlled in medium carbon 25Cr2Ni3MoV steel via multi-step tempering and partition (MTP) to achieve high cryogenic strength-ductility ...combinations. Microstructure evolution, the distribution of stress concentration, and microcrack formation and propagation during cryogenic Charpy impact testing were investigated. Compared with their performance in the quenching and tempering states (QT), the MTP steels showed a significant improvement in yield strength (1300 MPa), total elongation (25%), and impact toughness (>25 J) at liquid nitrogen temperature (LNT). The strengthening contributions mainly originated from the high dislocation density and refinement cementite (size: 70 nm) in the martensite lath (width: 1.5 μm) introduced by refined reversed austenite and its latter decomposition. The instrumented Charpy impact results indicated that cracks nucleated in the primary austenite grain (PAG) boundary for two steels due to the strain concentration band preferring to appear near PAGs, while cracks in the QT and MTP samples propagated along the PAGs and high-angle grain boundary (HAGB), respectively. The crystallized plasticity finite element simulation revealed that the PAG boundary with cementite precipitates of large size (>200 nm) was less able to dissipate crack propagation energy than the HAGBs by continuously forming a high strain concentration area, thus leading to the low-impact toughness of the QT steel.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Ischemic stroke is one of the main issues threatening human health worldwide, and it is also the main cause of permanent disability in adults. Energy consumption and hypoxia after ischemic stroke ...leads to the death of nerve cells, activate resident glial cells, and promote the infiltration of peripheral immune cells into the brain, resulting in various immune-mediated effects and even contradictory effects. Immune cell infiltration can mediate neuronal apoptosis and aggravate ischemic injury, but it can also promote neuronal repair, differentiation and regeneration. The central nervous system (CNS), which is one of the most important immune privileged parts of the human body, is separated from the peripheral immune system by the blood-brain barrier (BBB). Under physiological conditions, the infiltration of peripheral immune cells into the CNS is controlled by the BBB and regulated by the interaction between immune cells and vascular endothelial cells. As the immune response plays a key role in regulating the development of ischemic injury, neutrophils have been proven to be involved in many inflammatory diseases, especially acute ischemic stroke (AIS). However, neutrophils may play a dual role in the CNS. Neutrophils are the first group of immune cells to enter the brain from the periphery after ischemic stroke, and their exact role in cerebral ischemia remains to be further explored. Elucidating the characteristics of immune cells and their role in the regulation of the inflammatory response may lead to the identification of new potential therapeutic strategies. Thus, this review will specifically discuss the role of neutrophils in ischemic stroke from production to functional differentiation, emphasizing promising targeted interventions, which may promote the development of ischemic stroke treatments in the future.
Importance: Pathological perturbations of the brain often spread via connectome to fundamentally alter functional consequences. By integrating multimodal neuroimaging data with mathematical neural ...mass modeling, brain network models (BNMs) enable to quantitatively characterize aberrant network dynamics underlying multiple neurological and psychiatric disorders. We delved into the advancements of BNM-based medical applications, discussed the prevalent challenges within this field, and provided possible solutions and future directions. Highlights: This paper reviewed the theoretical foundations and current medical applications of computational BNMs. Composed of neural mass models, the BNM framework allows to investigate large-scale brain dynamics behind brain diseases by linking the simulated functional signals to the empirical neurophysiological data, and has shown promise in exploring neuropathological mechanisms, elucidating therapeutic effects, and predicting disease outcome. Despite that several limitations existed, one promising trend of this research field is to precisely guide clinical neuromodulation treatment based on individual BNM simulation. Conclusion: BNM carries the potential to help understand the mechanism underlying how neuropathology affects brain network dynamics, further contributing to decision-making in clinical diagnosis and treatment. Several constraints must be addressed and surmounted to pave the way for its utilization in the clinic.
The adverse impact of antibiotics on the gut microbiota has attracted extensive interest, particularly due to the development of microbiome research techniques in recent years. However, a direct ...comparison of the dynamic effects of various types of antibiotics using the same animal model has not been available. In the present study, we selected six antibiotics from four categories with the broadest clinical usage, namely, β-lactams (Ceftriaxone Sodium, Cefoperazone/Sulbactam and meropenem), quinolones (ofloxacin), glycopeptides (vancomycin), and macrolides (azithromycin), to treat BALB/c mice. Stool samples were collected during and after the administration of antibiotics, and microbial diversity was analyzed through Illumina sequencing and bioinformatics analyses using QIIME. Both α and β diversity analyses showed that ceftriaxone sodium, cefoperazone/sulbactam, meropenem and vancomycin changed the gut microbiota dramatically by the second day of antibiotic administration whereas the influence of ofloxacin was trivial. Azithromycin clearly changed the gut microbiota but much less than vancomycin and the β-lactams. In general, the community changes induced by the three β-lactam antibiotics showed consistency in inhibiting Papillibacter, Prevotella and Alistipes while inducing massive growth of Clostridium. The low diversity and high Clostridium level might be an important cause of Clostridium difficile infection after usage of β-lactams. Vancomycin was unique in that it inhibited Firmicutes, mainly the genus Clostridium. On the other hand, it induced the growth of Escherichia and effect lasted for months afterward. Azithromycin and meropenem induced the growth of Enterococcus. These findings will be useful for understanding the potential adverse effects of antibiotics on the gut microbiome and ensuring their better usage.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Vibrio parahaemolyticus is an important halophilous pathogen that can cause not only a broad range of disease in aquatic animals but also serious seafood-borne illness in humans as a result ...of the consumption of seafood. To avoid the use of antibiotics, it is critical to identify protective antigens for developing highly effective vaccines against this pathogen. Outer membrane proteins (OMPs) have been suggested as potential vaccine candidates for conferring protection against infection. In this study, we identified novel immunogenic OMPs using an immune assay with serum antibodies from mice infected by V. parahaemolyticus combined with mass spectrometry analysis. Nine OMPs were identified to be immunogenic proteins, and four of these identified proteins with relatively low abundance in OMP profiles, LptD, VP0802, VP1243 and VP0966, were determined to have immunogenicity for the first time. One OMP of interest, VP0802, is highly conserved among major Vibrio species and was proposed to adopt a β-barrel conformation and to be a member of the OprD protein family by bioinformatic analysis. The immunogenicity and protective efficacy of VP0802 were further evaluated by bacterial challenge postimmunization in a mouse model. VP0802 was confirmed to be highly immunogenic and to offer strong protection against V. parahaemolyticus infection, with an RPS of at least 66.7. Efficient clearance of bacteria from the blood of vaccinated mice was also observed. Moreover, upregulation of VP0802 expression was found after bacteria were exposed to fresh sera. These data, taken together, suggest that VP0802 is a promising candidate for the development of a subunit vaccine to prevent V. parahaemolyticus infection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Organic-inorganic hybrid halide materials have gained tremendous interest due to their unique optical, electrical, and magnetic properties. However, their large bandgaps limit their application. ...Here, we report a series of organic-inorganic hybrid halide semiconductors with rare and fully reversible thermochromatism, a narrow bandgap, and near-infrared luminescence. Through precise molecular modification, we successfully adjusted the bandgap from 1.910 to 2.120 eV and then achieved the effective temperature-derived modulation of the bandgap from 2.120 to 1.590 eV. Changing the temperature results in a reversible color change between yellow and purple-black. The intrinsic bandgap change is negligible after repeated heating/cooling cycles, indicating good thermal and environmental stability. Thermochromic behavior in hybrid structures is usually caused by lattice distortion, lattice expansion, or ion rearrangement. This work demonstrates efficient thermochromism leading to bandgap modulation, and it has great potential for intelligent window and temperature sensor applications. In addition, the thermochromism-induced bandgap narrowing provides new insights for the furthering of organic-inorganic hybrid halide materials.
Here, we report a series of organic-inorganic hybrid halide materials, with rare and fully reversible thermochromism, narrow bandgaps, and near-infrared luminescence. Thermochromism induced bandgap narrowing provide new insights for the further of organic-inorganic hybrid materials.
Summary
Previous studies have shown that subunits E (eIF3e), F (eIF3f) and H (elF3h) of eukaryotic translation initiation factor 3 play important roles in cell development in humans and yeast. eIF3e ...and eIF3h have also been reported to be important for normal cell growth in Arabidopsis. However, the functions of subunit eIF3f remain largely unknown in plant species. Here we report characterization of mutants for the Arabidopsis eIF3f (AteIF3f) gene. AteIF3f encodes a protein that is highly expressed in pollen grains, developing embryos and root tips, and interacts with Arabidopsis eIF3e and eIF3h proteins. A Ds insertional mutation in AteIF3f disrupted pollen germination and embryo development. Expression of some of the genes that are essential for pollen tube growth and embryogenesis is down‐regulated in ateif3f‐1 homozygous seedlings obtained by pollen rescue. These results suggested that AteIF3f might play important roles in Arabidopsis cell growth and differentiation in combination with eIF3e and eIF3h.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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