Organic–inorganic lead halide perovskites have recently emerged as highly competitive light absorbing materials for low cost solution-processable photovoltaic devices. With the high efficiency ...already achieved, removing the toxicity, i.e. , lead-free and stability are the key obstacles for perovskite solar cells. Here, we report the synthesis of an antimony (Sb)-based hybrid material having the composition of A 3 Sb 2 I 9 A = CH 3 NH 3 (MA), Cs and an investigation of its potential photovoltaic applications. Sb-based perovskite-like materials exhibited attractive absorbance properties, with the band gaps of MA 3 Sb 2 I 9 and Cs 3 Sb 2 I 9 measured to be 1.95 and 2.0 eV, respectively. X-ray photoelectron spectroscopy confirmed the formation of stoichiometric perovskites from appropriate precursor molar ratios incorporated with hydroiodic acid (HI). Planar hybrid Sb-based solar cells exhibited negligible hysteresis and reproducible power output under working conditions. A power conversion efficiency of 2.04% was achieved by the MA 3 Sb 2 I 9 perovskite-based device—the highest reported to date for a Sb-based perovskite solar cell.
FLASH radiotherapy (RT) is a novel technique in which the ultrahigh dose rate (UHDR) (≥40 Gy/s) is delivered to the entire treatment volume. Recent outcomes of in vivo studies show that the UHDR RT ...has the potential to spare normal tissue without sacrificing tumor control. There is a growing interest in the application of FLASH RT, and the ultrahigh dose irradiation delivery has been achieved by a few experimental and modified linear accelerators. The underlying mechanism of FLASH effect is yet to be fully understood, but the oxygen depletion in normal tissue providing extra protection during FLASH irradiation is a hypothesis that attracts most attention currently. Monte Carlo simulation is playing an important role in FLASH, enabling the understanding of its dosimetry calculations and hardware design. More advanced Monte Carlo simulation tools are under development to fulfill the challenge of reproducing the radiolysis and radiobiology processes in FLASH irradiation. FLASH RT may become one of standard treatment modalities for tumor treatment in the future. This paper presents the history and status of FLASH RT studies with a focus on FLASH irradiation delivery modalities, underlying mechanism of FLASH effect, in vivo and vitro experiments, and simulation studies. Existing challenges and prospects of this novel technique are discussed in this manuscript.
Background
Ultra‐high dose rate (FLASH) proton planning with only transmission beams (TBs) has limitations in normal tissue sparing. The single‐energy spread‐out Bragg peaks (SESOBPs) of the FLASH ...dose rate have been demonstrated feasible for proton FLASH planning.
Purpose
To investigate the feasibility of combining TBs and SESOBPs for proton FLASH treatment.
Methods
A hybrid inverse optimization method was developed to combine the TBs and SESOBPs (TB‐SESOBP) for FLASH planning. The SESOBPs were generated field‐by‐field from spreading out the BPs by pre‐designed general bar ridge filters (RFs) and placed at the central target by range shifters (RSs) to obtain a uniform dose within the target. The SESOBPs and TBs were fully placed field‐by‐field allowing automatic spot selection and weighting in the optimization process. A spot reduction strategy was conducted in the optimization process to push up the minimum MU/spot assuring the plan deliverability at beam current of 165 nA. The TB‐SESOBP plans were validated in comparison with the TB only (TB‐only) plans and the plans with the combination of TBs and BPs (TB‐BP plans) regarding 3D dose and dose rate (dose‐averaged dose rate) distributions for five lung cases. The FLASH dose rate coverage (V40Gy/s) was evaluated in the structure volume receiving > 10% of the prescription dose.
Results
Compared to the TB‐only plans, the mean spinal cord D1.2cc drastically reduced by 41% (P < 0.05), the mean lung V7Gy and V7.4 Gy moderately reduced by up to 17% (P < 0.05), and the target dose homogeneity slightly increased in the TB‐SESOBP plans. Comparable dose homogeneity was achieved in both TB‐SESOBP and TB‐BP plans. Besides, prominent improvements were achieved in lung sparing for the cases of relatively large targets by the TB‐SESOBP plans compared to the TB‐BP plans. The targets and the skin were fully covered with the FLASH dose rate in all three plans. For the OARs, V40Gy/s = 100% was achieved by the TB‐only plans while V40Gy/s > 85% was obtained by the other two plans.
Conclusion
We have demonstrated that the hybrid TB‐SESOBP planning was feasible to achieve FLASH dose rate for proton therapy. With pre‐designed general bar RFs, the hybrid TB‐SESOBP planning could be implemented for proton adaptive FLASH radiotherapy. As an alternative FLASH planning approach to TB‐only planning, the hybrid TB‐SESOBP planning has great potential in dosimetrically improving OAR sparing while maintaining high target dose homogeneity.
The cancer cell secretome may contain potentially useful biomarkers. In this study, we integrated the profiles of secreted proteins in lung cancer cell lines with mRNA expression levels from ...pulmonary adenocarcinoma tissue, with a view to identify effective biomarkers for non‐small cell lung cancer (NSCLC). Among the novel candidates isolated, importin subunit alpha‐2 (also known as karyopherin subunit alpha KPNA‐2), was selected for further validation. Immunohistochemical staining revealed overexpression of KPNA2 in the nuclei of tumor cells, compared with adjacent normal cells. A sandwich ELISA assay developed to detect KPNA2 levels in serum samples showed significantly higher serum KPNA2 in NSCLC patients than in healthy controls. A combination of serum KPNA2 and carcinoembryonic antigen displayed higher diagnostic capacity than either marker alone. Importantly, protein levels of KPNA2 in pleural effusion from NSCLC patients were also significantly higher than those from non‐lung cancer. Moreover, knockdown of KPNA2 inhibited the migration ability and viability of lung cancer cells. Our results collectively suggest that integration of the cancer cell secretome and transcriptome datasets provides an efficient means of identifying novel biomarkers for NSCLC, such as KPNA2.
Although sepsis and acute kidney injury (AKI) have a bidirectional interplay, the pathophysiological mechanisms between AKI and sepsis are not clarified and worthy of a comprehensive and updated ...review. The primary pathophysiology of sepsis-associated AKI (SA-AKI) includes inflammatory cascade, macrovascular and microvascular dysfunction, cell cycle arrest, and apoptosis. The pathophysiology of sepsis following AKI contains fluid overload, hyperinflammatory state, immunosuppression, and infection associated with kidney replacement therapy and catheter cannulation. The preventive strategies for SA-AKI are non-specific, mainly focusing on infection control and preventing further kidney insults. On the other hand, the preventive strategies for sepsis following AKI might focus on decreasing some metabolites, cytokines, or molecules harmful to our immunity, supplementing vitamin D3 for its immunomodulation effect, and avoiding fluid overload and unnecessary catheter cannulation. To date, several limitations persistently prohibit the understanding of the bidirectional pathophysiologies. Conducting studies, such as the Kidney Precision Medicine Project, to investigate human kidney tissue and establishing parameters or scores better to determine the occurrence timing of sepsis and AKI and the definition of SA-AKI might be the prospects to unveil the mystery and improve the prognoses of AKI patients.
Neuroinflammation with activation of microglia and production of proinflammatory cytokines in the brain plays an active role in epileptic disorders. Brain oxidative stress has also been implicated in ...the pathogenesis of epilepsy. Damage in the hippocampus is associated with temporal lobe epilepsy, a common form of epilepsy in human. Peripheral inflammation may exacerbate neuroinflammation and brain oxidative stress. This study examined the impact of peripheral inflammation on seizure susceptibility and the involvement of neuroinflammation and oxidative stress in the hippocampus.
In male, adult Sprague-Dawley rats, peripheral inflammation was induced by the infusion of Escherichia coli lipopolysaccharide (LPS, 2.5 mg/kg/day) into the peritoneal cavity for 7 days via an osmotic minipump. Pharmacological agents were delivered via intracerebroventricular (i.c.v.) infusion with an osmotic minipump. The level of cytokine in plasma or hippocampus was analyzed by ELISA. Redox-related protein expression in hippocampus was evaluated by Western blot. Seizure susceptibility was tested by intraperitoneal (i.p.) injection of kainic acid (KA, 10 mg/kg). We found that i.p. infusion of LPS for 7 days induced peripheral inflammation characterized by the increases in plasma levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). This is associated with a significant increase in number of the activated microglia (Iba-1(+) cells), enhanced production of proinflammatory cytokines (including IL-1β, IL-6 and TNF-α), and tissue oxidative stress (upregulations of the NADPH oxidase subunits) in the hippocampus. These cellular and molecular responses to peripheral inflammation were notably blunted by i.c.v. infusion of a cycloxygenase-2 inhibitor, NS398 (5 μg/μl/h). The i.c.v. infusion of tempol (2.5 μg/μl/h), a reactive oxygen species scavenger, protected the hippocampus from oxidative damage with no apparent effect on microglia activation or cytokine production after peripheral inflammation. In the KA-induced seizure model, i.c.v. infusion of both NS398 and tempol ameliorated the increase in seizure susceptibility in animals succumbed to the LPS-induced peripheral inflammation.
Together these results indicated that LPS-induced peripheral inflammation evoked neuroinflammation and the subsequent oxidative stress in the hippocampus, resulting in the increase in KA-induced seizure susceptibility. Moreover, protection from neuroinflammation and oxidative stress in the hippocampus exerted beneficial effect on seizure susceptibility following peripheral inflammation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Studies have discovered that different extracts of
and its phytochemicals show a variety of biological activities associated with inflammation. Although rutaecarpine, an alkaloid isolated from the ...unripe fruit of
, has been exposed to have anti-inflammatory properties, the mechanism of action has not been well studied. Thus, this study investigated the molecular mechanisms of rutaecarpine (RUT) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. RUT reserved the production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF-α), and interleukin (IL)-1β in the LPS-induced macrophages. RUT showed an inhibitory effect on the mitogen-activated protein kinases (MAPKs), and it also inhibited nuclear transcription factor kappa-B (NF-κB) by hindering IκBα and NF-κB p65 phosphorylation and p65 nuclear translocation. The phospho-PI3K and Akt was concentration-dependently suppressed by RUT. However, RUT not only suggestively reduced the migratory ability of macrophages and their numbers induced by LPS but also inhibited the phospho-Src, and FAK. Taken together, these results indicate that RUT participates a vital role in the inhibition of LPS-induced inflammatory processes in RAW 264.7 macrophages and that the mechanisms involve PI3K/Akt and MAPK-mediated downregulation of NF-κB signaling pathways. Notably, reducing the migration and number of cells induced by LPS via inhibiting of Src/FAK pathway was also included to the anti-inflammatory mechanism of RUT. Therefore, RUT may have potential benefits as a therapeutic agent against chronic inflammatory diseases.
A highly efficient electron transport layer (ETL) is an essential constituent for good performance and stability in planar perovskite solar cells. Among n-type metal oxide materials, zinc oxide (ZnO) ...is a promising candidate for an electron transport layer due to its relatively high electron mobility, high transparency, and versatile nanostructures. However, it was found that several disadvantages could occur at the ZnO/perovskite interface, such as decomposition of CH3NH3PbI3 and poorly aligned energy levels. To overcome these issues, we present a design based on staircase band alignment of a low-temperature solution-processed ZnO/Al-doped ZnO (AZO) bilayer thin film as electron transport layers in planar perovskite solar cells. Experimental results revealed that the power conversion efficiency (PCE) of perovskite solar cells was significantly increased from 12.3% to 16.1% by employing the AZO thin film as the buffer layer. Meanwhile, the short-circuit current density (J sc), open-circuit voltage (V oc), and fill factor (FF) were improved to 20.6 mA/cm2, 1.09 V, and 71.6%, respectively. The enhancement in performance is attributed to the modified interface in the ETL with staircase band alignment of ZnO/AZO/CH3NH3PbI3, which allows more efficient extraction of photogenerated electrons in the CH3NH3PbI3 active layer. Our studies demonstrated that the solution-processed ZnO/AZO bilayer ETLs provide a promising new approach for the development of low-cost, high-performance, and stable planar perovskite solar cells.
A chemical synthesis of ketopentose‐5‐phosphates that are involved in the pentose phosphate pathway has been developed. The ketopentose phosphates, d‐ribulose‐5‐phosphate and d‐xylulose‐5‐phosphate, ...were prepared in five steps starting from known intermediates. Starting from readily available d‐aldopentoses, reduction of the corresponding furanose derivatives gave key intermediates in the form of aldopentitols. Selective phosphorylation, oxidation, and deprotection provided the target molecules. This chemical synthesis makes such ketopentose phosphates readily available, and as a result they could be used as assay substrates for mechanistic studies. Since the pentose phosphate pathway is important in cancer‐cell metabolism, this synthetic approach provides an opportunity for preparing potential enzymatic inhibitors for use in drug development. To further extend this synthetic approach, a different protecting group (a trityl group) was used for the synthesis of the two parent ketopentoses (d‐ribulose and d‐xylulose) in a similar manner.
A chemical synthesis of ketopentose‐5‐phosphates that are involved in the pentose phosphate pathway has been developed. This method provides an efficient approach for the preparation of ketopentose‐5‐phosphates for enzymatic studies and potential drug development.
Purpose
Treatment planning systems (TPSs) from different vendors can involve different implementations of Monte Carlo dose calculation (MCDC) algorithms for pencil beam scanning (PBS) proton therapy. ...There are currently no guidelines for validating non‐water materials in TPSs. Furthermore, PBS‐specific parameters can vary by 1–2 orders of magnitude among different treatment delivery systems (TDSs). This paper proposes a standardized framework on the use of commissioning data and steps to validate TDS‐specific parameters and TPS‐specific heterogeneity modeling to potentially reduce these uncertainties.
Methods
A standardized commissioning framework was developed to commission the MCDC algorithms of RayStation 8A and Eclipse AcurosPT v13.7.20 using water and non‐water materials. Measurements included Bragg peak depth‐dose and lateral spot profiles and scanning field outputs for Varian ProBeam. The phase‐space parameters were obtained from in‐air measurements and the number of protons per MU from output measurements of 10 × 10 cm2 square fields at a 2 cm depth. Spot profiles and various PBS field measurements at additional depths were used to validate TPS. Human tissues in TPS, Gammex phantom materials, and artificial materials were used for the TPS benchmark and validation.
Results
The maximum differences of phase parameters, spot sigma, and divergence between MCDC algorithms are below 4.5 µm and 0.26 mrad in air, respectively. Comparing TPS to measurements at depths, both MC algorithms predict the spot sigma within 0.5 mm uncertainty intervals, the resolution of the measurement device. Beam Configuration in AcurosPT is found to underestimate number of protons per MU by ~2.5% and requires user adjustment to match measured data, while RayStation is within 1% of measurements using Auto model. A solid water phantom was used to validate the range accuracy of non‐water materials within 1% in AcurosPT.
Conclusions
The proposed standardized commissioning framework can detect potential issues during PBS TPS MCDC commissioning processes, and potentially can shorten commissioning time and improve dosimetric accuracies. Secondary MCDC can be used to identify the root sources of disagreement between primary MCDC and measurement.
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