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Perovskite solar cells (PSCs) have demonstrated rapid progress in their power conversion efficiencies (PCEs)—from 3.8% in 2009 to 25.7% in 2022—and they have received considerable attention as a promising future photovoltaic (PV) technology. However, the operational stability of PSCs is still inadequate to satisfy the standards for commercial applications. Interface engineering has become one of the most important strategies to push PSCs' efficiency and stability for practical use. Among the various interface engineering approaches, organic interface modifiers (OIMs) have been frequently used by the PSC field to address the issues limiting PSC stability at high efficiency levels. In this perspective, the chemical structures of state‐of‐the‐art OIMs are discussed, and their characteristics are reviewed, as well as the impact on device performance associated with key device interfaces (e.g., metal oxide/perovskite and organic transport layer/perovskite interfaces) from a chemical and materials engineering point of view is discussed. Design considerations and the authors' perspective are discussed, on the basis of representative literature examples, for building new, customized organic OIMs to further improve PSC efficiency and stability toward commercialization. [ABSTRACT FROM AUTHOR]

In this study, a reactive oxygen species (ROS)‐responsive hydrogel sensor (PD/MnO2 hydrogel) is developed that can efficiently detect senescent cells. Using immature murine articular chondrocytes with serial passages, the sensor can identify small interfering RNA (siRNA) knockdown of peroxisome proliferator‐activated receptor‐alpha (PPARα) based on the concentration of ROS in cells, simultaneously maintaining its balance via scavenging activity to prevent cartilage degradation in osteoarthritis (OA). The hydrogel sensor exhibits a change in electronic properties, with a distinct resistance from 201.9 kΩ for P0 to 362.9 kΩ for P3, and fluorescence off/on performance with an increase in passaging time. In vitro investigation using PPARα‐specific siRNA reveals a correlation between pressure sensitivity and senescent activity, wherein an elevation in observed signal occurred (41.5%). In vivo analysis reveals significant decrease in degradation of the cartilage of both young, 3 months old aged, 18 months old, and PPARα−/− mice compared to PPARα+/+ mice based on safranin O stains. The expression level of interleukin‐1β is reduced in the cartilage of aged PPARα−/− mice after implantation with hydrogel, indicating the potential of PD/MnO2 hydrogel as a therapeutic modality against OA. [ABSTRACT FROM AUTHOR]

The estrogen-like effect of bisphenol A (BPA) disrupting the maintenance of functional male germ cells is associated with male sub-fertility. This study investigated toxicity of male germ cells induced by four bisphenol analogs: BPA, BPAF, BPF, and BPS. The investigation of bisphenol analogs' impact on male germ cells included assessing proliferation, apoptosis induction, and the capacity to generate reactive oxygen species (ROS) in GC-1 spermatogonia (spg) cells, specifically type B spermatogonia. Additionally, the therapeutic potential and protective effects of N-Acetyl Cysteine (NAC) and NF-κB inhibitor parthenolide was evaluated. In comparison to BPA, BPF and BPS, BPAF exhibited the most pronounced adverse effect in GC-1 spg cell proliferation. This effect was characterized by pronounced inhibition of phosphorylation of PI3K, AKT, and mTOR, along with increased release of cytochrome c and subsequent cleavages of caspase 3, caspase 7, and poly (ADP-ribose) polymerase. Both NAC and parthenolide were effective reducing cellular ROS induced by BPAF. However, only NAC demonstrated a substantial recovery in proliferation, accompanied by a significant reduction in cytochrome c release and cleaved PARP. These results suggest that NAC supplementation may play an effective therapeutic role in countering germ cell toxicity induced by environmental pollutants with robust oxidative stress-generating capacity. [Display omitted] [ABSTRACT FROM AUTHOR]

Vascular smooth muscle cell (VSMC) senescence promotes atherosclerosis via lipid-mediated mitochondrial dysfunction and oxidative stress. However, the mechanisms of mitochondrial dysfunction and VSMC senescence in atherosclerosis have not been established. Here, we investigated the mechanisms whereby signaling pathways regulated by SRT1720 enhance or regulate mitochondrial functions in atherosclerotic VSMCs to suppress atherosclerosis. Initially, we examined the effect of SRT1720 on oleic acid (OA)-induced atherosclerosis. Atherosclerotic VSMCs exhibited elevated expressions of BODIPY and ADRP (adipose differentiation-related protein) and associated intracellular lipid droplet markers. In addition, the expression of collagen I was upregulated by OA, while the expressions of elastin and α-SMA were downregulated. mtDNA copy numbers, an ATP detection assay, transmission electron microscopy (TEM) imaging of mitochondria, mitochondria membrane potentials (assessed using JC-1 probe), and levels of mitochondrial oxidative phosphorylation (OXPHOS) were used to examine the effects of SRT1720 on OA-induced mitochondrial dysfunction. SRT1720 reduced mtDNA damage and accelerated mitochondria repair in VSMCs with OA-induced mitochondria dysfunction. In addition, mitochondrial reactive oxygen species (mtROS) levels were downregulated by SRT1720 in OA-treated VSMCs. Importantly, SRT1720 significantly increased SIRT1 and PGC-1α expression levels, but VSMCs senescence, inflammatory response, and atherosclerosis phenotypes were not recovered by treating cells with EX527 and SR-18292 before SRT1720. Mechanistically, the upregulations of SIRT1 and PGC-1α deacetylation by SRT1720 restored mitochondrial function, and consequently suppressed VSMC senescence and atherosclerosis-associated proteins and phenotypes. Collectively, this study indicates that SRT1720 can attenuate OA-induced atherosclerosis associated with VSMC senescence and mitochondrial dysfunction via SIRT1-mediated deacetylation of the PGC-1α pathway. [Display omitted] • SRT1720 reduced proteins and phenotypes involved in oleic acid (OA)-induced pathogenesis of atherosclerosis. • SIRT1 activation by SRT1720 deacetylated PGC-1α in OA-treated vascular smooth muscle cells (VSMCs). • SRT1720 restored mitochondrial dysfunction and improved mitochondrial membrane potential in OA-treated VSMCs. • SRT1720 suppressed senescence-associated atherosclerosis progression via SIRT1-dependent PGC-1α deacetylation pathway. [ABSTRACT FROM AUTHOR]

The epidermal growth factor receptor (EGFR) is over-expressed in various human cancer. The over-expression of EGFR in tumors is an excellent target for the development of cancer imaging agents. In the present study, we developed Tc-99m SYPIPDT-GHEG-ECG-K-tetramethylrhodamine (SYPIPDT-ECG-TAMRA) as a molecular imaging agent targeting wild-type EFGR (wtEGFR)-positive tumor cells, and verified its feasibility as molecular imaging agent. SYPIPDT-ECG-TAMRA was synthesized using Fmoc solid-phase peptide synthesis. The radiolabeling of SYPIPDT-ECG-TAMRA with Tc-99m was accomplished using ligand exchange via tartrate. Cellular uptake and binding affinity studies were performed. In vivo gamma camera imaging, ex vivo imaging and biodistribution studies were performed using NCI-H460 and SW620 tumor-bearing murine models. After radiolabeling procedures with Tc-99m, Tc-99m SYPIPDT-ECG-TAMRA complexes were prepared at high yield (> 95%). The binding affinity value (Kd) of Tc-99m SYPIPDT-ECG-TAMRA for NCI-H460 cells was estimated to be 76.5 ± 15.8 nM. In gamma camera imaging, the tumor to normal muscle uptake ratios of Tc-99m SYPIPDT-ECG-TAMRA increased with time (2.7 ± 0.6, 4.0 ± 0.9, and 6.2 ± 1.0 at 1, 2, and 3 h, respectively). The percentage injected dose per gram of wet tissue for the NCI-H460 tumor was 1.91 ± 0.11 and 1.70 ± 0.22 at 1 and 3 h, respectively. We developed Tc-99m SYPIPDT-ECG-TAMRA, which is dual-labeled with both radioisotope and fluorescence. In vivo and in vitro studies demonstrated specific uptake of Tc-99m SYPIPDT-ECG-TAMRA into wtEGFR-positive NCI-H460 cells and tumors. Thus, the results of the present study suggest that Tc-99m SYPIPDT-ECG-TAMRA is a potential dual-modality imaging agent targeting wtEGFR. [ABSTRACT FROM AUTHOR]

The objective of this study was to report the synthesis and characteristics of a dual modality imaging agent, Tc‐99m GRFLTGGTGRLLRIS‐GHEG‐ECG‐K(‐5‐carboxy‐X‐rhodamine)‐NH2 (GRFLT‐ECG‐ROX), and to verify its feasibility as both molecular imaging and intraoperative guidance agent. GRFLT‐ECG‐ROX was synthesized using Fmoc solid‐phase peptide synthesis. Radiolabeling of GRFLT‐ECG‐ROX with Tc‐99m was accomplished using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed using LNCaP and PC‐3 tumor‐bearing murine models. Surgical removal of tumor nodules in murine models with peritoneal carcinomatosis was performed under a fluorescence imaging system. After radiolabeling procedures with Tc‐99m, Tc‐99m GRFLT‐ECG‐ROX complexes were prepared in high yield (>96%). The binding affinity value (Kd) of Tc‐99m GRFLT‐ECG‐ROX for LNCaP cells was estimated to be 9.5 ± 1.3 nM. In gamma camera imaging, the tumor to normal muscle uptake ratios of Tc‐99m GRFLT‐ECG‐ROX increased with time (3.1 ± 0.2, 4.0 ± 0.4, and 6.3 ± 0.9 at 1, 2, and 3 h, respectively). Under real‐time optical imaging, the removal of visible nodules was successfully performed. Thus, Tc‐99m GRFLT‐ECG‐ROX could provide both preoperative molecular imaging and fluorescence imaging guidance for tumor removal. [ABSTRACT FROM AUTHOR]

Cellular senescence is associated with inflammation and the senescence-associated secretory phenotype (SASP) of secreted proteins. Vascular smooth muscle cell (VSMC) expressing the SASP contributes to chronic vascular inflammation, loss of vascular function, and the developments of age-related diseases. Although VSMC senescence is well recognized, the mechanism of VSMC senescence and inflammation has not been established. In this study, we aimed to determine whether prednisolone (PD) attenuates adriamycin (ADR)-induced VSMC senescence and inflammation through the SIRT1-AMPK signaling pathway. We found that PD inhibited ADR-induced VSMC senescence and inflammation response by decreasing p-NF-κB expression through the SIRT1-AMPK signaling pathway. In addition, Western blotting revealed PD not only increased SIRT1 expression but also increased the phosphorylation of AMPK at Ser485 in ADR-treated VSMC. Furthermore, siRNA-mediated downregulation or pharmacological inhibitions of SIRT1 or AMPK significantly augmented ADR-induced inflammatory response and senescence in VSMC despite PD treatment. In contrast, the overexpression of SIRT1 or constitutively active AMPKα (CA-AMPKα) attenuated cellular senescence and p-NF-κB expression. Taken together, the inhibition of p-NF-κB by PD through the SIRT1 and p-AMPK (Ser485) pathway suppressed VSMC senescence and inflammation. Collectively, our results suggest that anti-aging effects of PD are caused by reduced VSMC senescence and inflammation due to reciprocal regulation of the SIRT1/p-AMPK (Ser485) signaling pathway. [ABSTRACT FROM AUTHOR]

This study reports the aging effect of a perovskite precursor solution on the photovoltaic performance of perovskite solar cells. The precursor solution is aged at different temperatures of 4, 25 (room temperature), and 65 °C. Power conversion efficiency (PCE) is found to depend on the aging condition. Average PCE increases with aging time, where optimal aging time for best the PCE decreases with aging temperature. Average PCE of 17.29% obtained from a 24 h aged solution at 4 °C is higher than that of 16.48% from a nonaged fresh solution. At 25 °C, a 2–4 h aged solution yields highest PCE of 17.41%. The aging effect is more accelerated at 65 °C, where the best PCE of around 17.10% is achieved from the solution aged for 1.5–2 h. It is commonly observed that photocurrent density is substantially influenced by aging time, while voltage is less affected. Fill factor declines with aging time regardless of aging temperature. Iodoplumbate PbI2S4 (S = solvent) formed in the precursor solution increases its concentration, as aging time increases at a given temperature, which is beneficial for improving photovoltaic performance. No aging effect is found for excess MAI or PbI2 due to initially formed sufficient iodoplumbate. [ABSTRACT FROM AUTHOR]

[Display omitted] Cellular senescence is caused by diverse stimuli and contributes to cardiovascular diseases. Several studies have indicated that PPARγ acts as a key mediator of lipid metabolism and shown that it has a protective effect on vascular biology. Nevertheless, the mechanism responsible for the anti-aging effects of PPARγ has not been fully elucidated in vascular smooth muscle cell (VSMC). Furthermore, although mTOR complex 2 (mTORC2) is known to be involved in cellular senescence and autophagy, relatively few studies have investigated its effects as compared with mTOR complex 1 (mTORC1). Therefore, we focused on mTORC2 function and investigated the relationship between PPARγ and mTORC2, and the anti-aging mechanism in VSMC. We found PPARγ activation dose-dependently mitigated the hydrogen peroxide (H 2 O 2)-induced senescence. Treatment of fisetin induced the translocation of PPARγ from cytosol to nuclear and inhibited VSMC senescence. Moreover, activated PPARγ increased PTEN transcription, leading to inhibition of the mTORC2 signaling pathway. We determined mTORC2 activation contributed to senescence by suppressing the FoxO3a-autophagy signaling pathway, and dual knockdown of mTORC1 and mTORC2 decreased cellular senescence and increased autophagy activation more than respective single knockdown. Finally, fisetin acted as a PPARγ activator and inhibited VSMC senescence through the mTORC2-FoxO3a-autophagy signaling pathway. These results demonstrate PPARγ is associated with cellular senescence and that fisetin has an anti-aging effect via PPARγ activation and mTORC2 inhibition in VSMC. These results demonstrate that the mTORC2 signaling pathway regulates autophagy and cellular senescence, which suggests mTORC2 should be considered a significant target for preventing cellular senescence and age-related diseases. [ABSTRACT FROM AUTHOR]

Introduction: A pulled elbow is a common cause of acute elbow pain that is generally managed by a reduction maneuver without radiographic examination. However, children with atypical presentation with no history of abrupt longitudinal traction should undergo elbow imaging. This study aimed to investigate plain radiography findings and determine the usefulness of ultrasonography (US) in atypical pulled elbow.Materials and Methods: We retrospectively reviewed the medical records and images of 37 (22 males) consecutive patients with pulled elbow who presented with an atypical history or failed reduction between April 2015 and September 2018. Mean age at presentation was 4.34 years (range, 1.25-9.5 years). Of the 37 elbows, 20 were left elbows. The injury mechanism, incidence of the posterior fat pad sign on plain radiographs, and characteristic US findings, pre- and post- reduction, were investigated.Results: The original mechanisms of injury included slipping (n = 14), rolling over the arm (n = 7), vague history (n = 6), falling down (n = 6), abrupt longitudinal traction (n = 2), and direct injury (n = 2). On plain radiographs, six of the 37 elbows (16%) showed the posterior fat pad sign. Before the reduction, an entrapped supinator, a pathognomonic sign of pulled elbow, was identified on US in all cases. After reduction, the characteristic US findings showed a disentangled and swollen supinator (100%) and restored annular ligament (100%) in all successful cases. Although a click was not felt in three cases, the reductions were considered successful because the annular ligament was restored on US with free elbow motion.Conclusion: Pulled elbow may be caused by atypical mechanisms of injury, such as slipping and rolling over the arm. Clinicians should be aware of the possibility of the posterior fat pad sign on plain radiographs of pulled elbow to prevent unnecessary immobilization. In such circumstances, US is a useful method for detecting an entrapped supinator and confirming adequate reduction via restoration of the annular ligament in children with atypical pulled elbow. [ABSTRACT FROM AUTHOR]

Abstract A pellicle is an important part of mask protection in extreme ultraviolet (EUV) lithography, and nanometer-thickness graphite film (NGF) is an ideal material for pellicle fabrication. In our previous work, we synthesized large-scale NGF on polycrystalline Ni foil by a "two-stage" chemical vapor deposition process with an EUV transmittance of 79 ± 2%. The nonuniformity of EUV transmittance is mainly caused by the thicker NGF formed on the Ni grain boundaries (GBs). Here, we present a simple and cost-effective method to weaken the effects of the Ni GBs by sputtering thin Ni films onto Ni foils. The Ni film provides smaller grains with high GB density so that the non-uniformity of NGFs caused by Ni GBs was averaged out by the large EUV beam size. We investigated the grain growth of Ni films with different thicknesses, and 1-μm Ni film/Ni foil had the minimum average grain size of ∼6 μm. The NGF synthesized on it showed a higher EUV transmittance with better uniformity of 86.3 ± 0.9%. Fullerenic C C and sp3 C C bonding were detected by the X-ray photoelectron spectroscopy, and the NGF on the Ni GBs showed a higher defect density. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

[Display omitted] • Pyrophosphate-responsive self-reporting hydrogel is designed for cancer detection. • Signaling of self-reporting sensor produced distinct viscoelasticity & conductivity. • Cu2+-PPi interaction triggered change in pore structure of PD-Cu2+@PAA hydrogel. • PPi-Cu2+ complexation induced fluorescence recovery in cancer cell-treated hydrogel. • Cancer cell-treated hydrogel showed irreversible pressure response than normal cell. A pyrophosphate-responsive self-reporting mineralized hydrogel sensor was designed for simple naked-eye monitoring of cancer cells. The sensor utilized physical form alteration mediated via changes in viscoelasticity, shape, stretchability, and changes in fluorescence as well as the conductivity of hydrogel. The incorporation of copper ion-immobilized polymer dots (PD-Cu2+) into the mineralized polyacrylic acid (PAA) hydrogel produced a self-reporting ability to differentiate between cancer and normal cells in response to different levels of pyrophosphate (PPi) in cancer and normal cells. The detachment of Cu in PD-Cu2+@PAA mineralized hydrogel by PPi resulted in a fluid-like, softer, and injectable hydrogel after treatment with cancer cells (HeLa, KG-1) compared to that observed in normal cells (CHO-K1) in the presence of ALP inhibitor. Furthermore, the Cu2+-PPi interaction recovered the fluorescence and decreased the conductivity of hydrogel; the resistance changes in HeLa (ΔR = 380 Ω) and KG-1-treated PD-Cu2+@PAA mineralized hydrogels (ΔR = 390 Ω) were higher than those of CHO-K1-treated PD-Cu2+@PAA mineralized hydrogel (ΔR = 80 Ω) with and without ALP inhibitor. Moreover, the wireless sensing system revealed that cancer cell-treated hydrogel showed an irreversible pressure response compared with normal cell-treated hydrogel. Thus, this self-reporting hydrogel has the potential to be applied to point-of-care cancer diagnostics. [ABSTRACT FROM AUTHOR]

(1) Background: The coronavirus disease 2019 (COVID-19) pandemic has proven challenging to the management of patients with cancer, particularly those receiving systemic therapy. This study aimed to evaluate the impact of COVID-19 on patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab/bevacizumab. (2) Methods: Patients with unresectable HCC who started atezolizumab/bevacizumab treatment between June 2020 and December 2021 at a tertiary cancer center in Korea were included (n = 241) and classified according to their COVID-19 status and severity. (3) Results: Thirty-five (14.5%) patients with unresectable HCC were diagnosed with COVID-19 during atezolizumab/bevacizumab treatment; 26 (74.2%) and nine (25.7%) in the low- and high-severity groups, respectively. The high-severity group showed higher neutrophil-to-lymphocyte ratios and lactate dehydrogenase levels. Liver and kidney injuries were observed in 31.4% and 17.1% of total patients, respectively. Liver injury was more prominent in patients with pre-existing liver dysfunction at baseline, who were more prevalent in the high-severity group. Atezolizumab/bevacizumab treatment was delayed by a median of 0 (range, 0–21) day in the low-severity group and 12 (range, 0–35) days in the high-severity group. The high-severity group showed worse post-infection progression-free survival (1.1 vs. 4.8 months, p = 0.017) and overall survival (2.2 months vs. not reached, p = 0.004). (4) Conclusions: Patients with impaired liver function at baseline are more susceptible to high-severity COVID-19, which affects atezolizumab/bevacizumab treatment outcomes. [ABSTRACT FROM AUTHOR]

We developed a Tc‐99m and TAMRA‐labeled peptide, Tc‐99m arginine‐arginine‐leucine (RRL) peptide (TAMRA‐GHEG‐ECG‐RRL), to target tumor cells and evaluated the diagnostic performance of Tc‐99m TAMRA‐GHEG‐ECG‐RRL as a dual‐modality imaging agent for tumor in a murine model. TAMRA‐GHEG‐ECG‐RRL was synthesized using Fmoc solid‐phase peptide synthesis. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed in murine models with PC‐3 tumors. Tumor tissue slides were prepared and analyzed with immunohistochemistry using confocal microscopy. After radiolabeling procedures with Tc‐99m, Tc‐99m TAMRA‐GHEG‐ECG‐RRL complexes were prepared in high yield (>96%). The Kd of Tc‐99m TAMRA‐GHEG‐ECG‐RRL determined by saturation binding was 41.7 ± 7.8 nM. Confocal microscopy images of PC‐3 cells incubated with TAMRA‐GHEG‐ECG‐RRL showed strong fluorescence in the cytoplasm. Gamma camera imaging revealed substantial uptake of Tc‐99m TAMRA‐GHEG‐ECG‐RRL in tumors. Tumor uptake was effectively blocked by the coinjection of an excess concentration of RRL. Specific uptake of Tc‐99m TAMRA‐GHEG‐ECG‐RRL was confirmed by biodistribution, ex vivo imaging, and immunohistochemistry stain studies. In conclusion, in vivo and in vitro studies revealed substantial uptake of Tc‐99m TAMRA‐GHEG‐ECG‐RRL in tumors. Tc‐99m TAMRA‐GHEG‐ECG‐RRL has potential as a dual‐modality tumor imaging agent. [ABSTRACT FROM AUTHOR]

Background: Quantitative assessment of rotator cuff muscle activity is important in the treatment of shoulder disorders. However, the known methods for assessing rotator cuff muscle activity thus far have been inaccurate, invasive, and inconvenient.Questions/purposes: (1) Does the activity of the deltoid, supraspinatus, and infraspinatus muscles measured using ultrasound shear wave elastography have a linear correlation with muscle activity assessed using generally used methods, including isokinetic dynamometry and electromyography? (2) Does the activity of the deltoid, supraspinatus, and infraspinatus muscles measured using shear wave elastography show good intraobserver and interobserver reliability?Methods: Twelve volunteers participated in intrasession reliability experiments. They were asked to perform isometric abduction, external rotation, and scaption contractions (defined as elevation of the arm within the plane of the scapula with neutral arm rotation) gradually increased from 0% to 75% of maximal voluntary contraction. The joint torque, electromyographic activity, and shear elastic modulus were synchronously measured in the middeltoid, supraspinatus, and infraspinatus muscles. The validity of the elastic modulus value was assessed using regression analysis between normalized torque and electromyographic root mean square values. For intraobserver and interobserver reliability measurements, repeated experiments were performed with the same protocol.Results: The shear elastic modulus and normalized joint torque with isokinetic dynamometry showed a linear relationship in all muscles (deltoid, supraspinatus, and infraspinatus) and each of the ultrasonography planes (longitudinal and transverse) (mean R > 0.8 and p < 0.001 for all measurements). For the supraspinatus muscle, the mean slope of the relationship between shear elastic modulus in the longitudinal plane and the normalized joint torque during scaption contraction was 1.28 ± 0.39 kPa/%MVC (mean R = 0.93 ± 0.21, p < 0.001). Furthermore, similar results were obtained in relation to electromyography root mean square values (mean R > 0.8 and p < 0.001 in all measurements). For the supraspinatus muscle, the mean slope of the relationship between shear elastic modulus in the longitudinal plane and electromyographic (EMG) root mean square was 0.96 ± 0.27 kPa/%EMG (mean R = 0.91 ± 0.08, p < 0.001). The intraobserver and interobserver reliabilities were excellent in all positions (abduction, external rotation, and scaption) and in both the longitudinal and transverse ultrasonography planes (all intraclass correlation coefficients are > 0.85).Conclusions: Shoulder muscle activity can be noninvasively evaluated with ultrasound shear wave elastography. Clinician and scientists should consider the application of this technique in cases in which evaluation of shoulder muscle activity is required. The next step after this study will be to check the shear elastic modulus of rotator cuff muscle in patients with rotator cuff tear. We plan to evaluate the correlation between shear elastic modulus and joint torque according to tear size and fatty infiltration status of rotator cuff muscle.Clinical Relevance: Shear wave electrography can be used to measure various tissue elasticities in both static and dynamic modes. It may be a useful tool to evaluate pre- and postoperative rotator cuff muscle activity in a relatively simple manner. Shoulder function after reverse total shoulder arthroplasty associated with deltoid muscle activity also may be evaluated. Changes in tissue tightness in shoulder disorders caused by increase soft tissue stiffness (ie, adhesive capsulitis and glenohumeral internal rotation deficit) can be evaluated. [ABSTRACT FROM AUTHOR]

Large-scale graphitic thin film with high thickness uniformity needs to be developed for industrial applications. Graphitic films with thicknesses ranging from 3 to 20 nm have rarely been reported, and achieving the thickness uniformity in that range is a challenging task. In this study, a process for growing 20 nm-thick graphite films on Ni with improved thickness uniformity is demonstrated and compared with the conventional growth process. In the film grown by the process, the surface roughness and coverage were improved and no wrinkles were observed. Observations of the film structure reveal the reasons for the improvements and growth mechanisms. [ABSTRACT FROM AUTHOR]

The vascular tone plays an important role in blood pressure and flow. It is influenced by the contraction of vascular smooth muscle cells (VSMCs), which in turn is regulated by the balance between the myosin light chain kinase (MLCK) and the phosphorylated myosin light chain (p-MLC). Quercetin is a common flavonoid which is found in many fruits and red wine. Although quercetin has been widely reported to be involved in cell proliferation, migration, and apoptosis in VSMCs, it has not yet been demonstrated whether quercetin is related to vasocontraction, a function regulated by the AMP-activated protein kinase (AMPK) signaling pathway. Accordingly, the aim of this study is to investigate the molecular mechanism through which the quercetin-activated LKB1-AMPK signaling pathway regulates the contraction of VSMCs. In cultured VSMCs, quercetin activated AMPK in a dose- and time-dependent manner. Quercetin inhibited the phenylephrine (PE)-induced expression of MLCK and p-MLC through the LKB1-AMPK signaling pathway and decreased the mRNA level of MLCK. Adenovirus-AMPK DN α1 and AMPK DN α2-transduced VSMCs displayed higher p-MLC expression. Moreover, quercetin inhibited the PE-mediated contraction in rat aorta. These data suggest that the quercetin-activated LKB1-AMPK signaling pathway regulates VSMC contraction by inhibiting MLCK and p-MLC; hence, it may be a therapeutic intervention for the treatment of cardiovascular disorders such as atherosclerosis and hypertension. [ABSTRACT FROM AUTHOR]

Organic -- inorganic halide perovskite is believed to be a potential candidate for high efficiency solar cells because power conversion efficiency (PCE) was certified to be more than 22%. Nevertheless, mismatch of PCE due to current density (J) -- voltage (V) hysteresis in perovskite solar cells is an obstacle to overcome. There has been much lively debate on the origin of J -- Vhysteresis; however, effective methodology to solve the hysteric problem has not been developed. Here we report a universal approach for hysteresis-free perovskite solar cells via defect engineering. A severe hysteresis observed from the normal mesoscopic structure employing TiO[sub 2] and spiro-MeOTAD is almost removed or does not exist upon doping the pure perovskites, CH[sub 3]NH[sub 3]PbI[sub 3] and HC(NH[sub 2])[sub 2]PbI[sub 3], and the mixed cation/anion perovskites, FA[sub 0.85]MA[sub 0.15]PbI[sub 2.55]Br[sub 0.45] and FA[sub 0.85]MA[sub 0.1]Cs[sub 0.05]PbI[sub 2.7]Br[sub 0.3], with potassium iodide. Substantial reductions in low-frequency capacitance and bulk trap density are measured from the KI-doped perovskite, which is indicative of trap-hysteresis correlation. A series of experiments with alkali metal iodides of LiI, NaI, KI, RbI and CsI reveals that potassium ion is the right element for hysteresis-free perovskite. Theoretical studies suggest that the atomistic origin of the hysteresis of perovskite solar cells is not the migration of iodide vacancy but results from the formation of iodide Frenkel defect. Potassium ion is able to prevent the formation of Frenkel defect since K[sup +] energetically prefers the interstitial site. A complete removal of hysteresis is more pronounced at mixed perovskite system as compared to pure perovskites, which is explained by lower formation energy of K interstitial (-0.65 V for CH[sub 3]NH[sub 3]PbI[sub 3] vs -1.17 V for mixed perovskite). The developed KI doping methodology is universally adapted for hysteresis-free perovskite regardless of perovskite composition and device structure. [ABSTRACT FROM AUTHOR]

We developed an electrochemical and fluorescent dual-mode sensor for assessing acetylcholinesterase (AChE) activity and inhibition by taking advantage of the high redox sensitivity of surface-coated mesoporous MnO 2 @polymer dot (MnO 2 @PD) towards AChE. The following phenomena constitute the basis of the detection mechanism: fluorescence resonance energy transfer (FRET) effect between MnO 2 and PD; catalytic hydrolysis of acetylthiocholine (ATCh) to thiocholine (TCh) by AChE expressed by PC-12 cells, inducing fluorescence restoration and change in the conductivity of the system due to MnO 2 decomposition; the presence of the inhibitor neostigmine preventing the conversion of ATCh to TCh. The surface-coated biosensor presents both fluorescence-based and electrochemical approaches for effectively monitoring AChE activity and inhibition. The fluorescence approach is based on the fluorescent "on/off" property of the system caused by MnO 2 breakdown after interaction with TCh and the subsequent release of PDs. The conductivity of the coated electrode decreased dramatically as AChE concentration increased, resulting in electrochemical sensing of AChE activity and inhibition screening. Real-time wireless sensing can be conducted using a smartphone to monitor the resistance change, investigating the potential use of MnO 2 @PD nanocomposites in biological studies, and offering a real-time redox-fluorescent test for AChE activity monitoring and inhibitor screening. [Display omitted] • Electrochemical and fluorescent-based surface-coated MnO 2 @PD for AChE sensing. • Electronic/optical properties affected by breakdown of MnO 2 in the presence of AChE. • In vitro assessment of AChE using PC-12 cells exhibiting high AChE expression. • Monitor neostigmine inhibition of AChE via fluorescence and electronic signals. • Real-time wireless sensing to facilitate the detection of AChE via a smartphone. [ABSTRACT FROM AUTHOR]

• VSMC senescence was accompanied by decreased PTEN and increased PKCδ phosphorylation. • PKCδ activates NOX1, leading to ROS production and cellular senescence in VSMC. • Fisetin is a polyphenol with antioxidant, anti-inflammatory, and anti-cancer effects. • Fisetin alleviates senescence through PTEN mediated inhibition of PKCδ-NOX1 in VSMC. Reactive oxygen species (ROS) are a key risk factor of cellular senescence and age-related diseases, and protein kinase C (PKC) has been shown to activate NADPH oxidases (NOXs), which generate ROS. Although PKC activation induces oxidative stress, leading to the cellular dysfunction in various cell types, the correlation between PKC and senescence has not been reported in vascular smooth muscle cell (VSMC). Several studies have indicated cellular senescence is accompanied by phosphatase and tensin homolog (PTEN) loss and that an interaction exists between PTEN and PKC. Therefore, we aimed to determine whether PTEN and PKC are associated with VSMC senescence and to investigate the mechanism involved. We found hydrogen peroxide (H 2 O 2) decreased PTEN expression and increased PKCδ phosphorylation. Moreover, H 2 O 2 upregulated the NOX1 subunits, p22phox and p47phox, and induced VSMC senescence via p53-p21 signaling pathway. We identified PKCδ activation contributed to VSMC senescence through activation of NOX1 and ROS production. However, fisetin inhibited cellular senescence induced by the PTEN-PKCδ-NOX1-ROS signaling pathway, and this anti-aging effect was attributed to reduced ROS production caused by suppressing NOX1 activation. These results suggest that the PTEN-PCKδ signaling pathway is directly related to senescence via NOX1 activation and that the downregulation of PKCδ by flavonoids provides a potential means of treating age-associated diseases. [ABSTRACT FROM AUTHOR]

Anomalous current–voltage (J–V) hysteresis in perovskite (PSK) solar cell is open to dispute, where hysteresis is argued to be due to electrode polarization, dipolar polarization, and/or native defects. However, a correlation between those factors and J–V hysteresis is hard to be directly evaluated because they usually coexist and are significantly varied depending on morphology and crystallinity of the PSK layer, selective contacts, and device architecture. In this study, without changing morphology and crystallinity of PSK layer in a planar heterojunction structure employing FA0.9Cs0.1PbI3, a correlation between J–V hysteresis and trap density is directly evaluated by means of thermally induced PbI2 regulating trap density. Increase in thermal annealing time at a given temperature of 150 °C induces growth of PbI2 on the PSK grain surface, which results in significant reduction of nonradiative recombination. Hysteresis index is reduced from 0.384 to 0.146 as the annealing time is increased from 5 to 100 min due to decrease in the amplitude of trap-mediated recombination. Reduction of hysteresis by minimizing trap density via controlling thermal annealing time leads to the stabilized PCE of 18.84% from the normal planar structured FA0.9Cs0.1PbI3 PSK solar cell. [ABSTRACT FROM AUTHOR]

The serine-aspartic acid-valine (SDV) peptide binds specifically to integrin αvβ3. We developed a Tc-99 m and TAMRA labeled peptide, Tc-99 m SDV-ECG-K-TAMRA for multimodal imaging of angiogenesis. Tc-99 m SDV-ECG-K-TAMRA was prepared in high yield (>96%) and showed low cytotoxicity. Tc-99 m tetrofosmin images 1 week after operation, revealed significantly decreased perfusion of the ischemic hindlimb, and the perfusion recovered gradually for 4 weeks. In contrast, Tc-99 m SDV-ECG-K-TAMRA uptake was maximal 1 week after the operation (ischemic-to-non-ischemic uptake ratio =5.03±1.01) and decreased gradually. The ischemic-to-non-ischemic ratio of Tc-99 m SDV-ECG-K-TAMRA and Tc-99 m tetrofosmin was strongly negatively correlated (r =−0.94). A postmortem analysis revealed increased angiogenesis markers and uptake of Tc-99 m SDV-ECG-K-TAMRA by ischemic tissue. Our in vivo and in vitro studies revealed substantial uptake of Tc-99 m SDV-ECG-K-TAMRA by ischemic tissue. Tc-99 m SDV-ECG-K-TAMRA could be a good candidate dual-modality imaging agent to assess angiogenesis. [ABSTRACT FROM AUTHOR]

In this work, large-scale (120 × 120 mm) nanometer-thick graphite films (NGFs) were synthesized on polycrystalline Ni foils using a “two-stage” chemical vapor deposition (CVD) process. An intermediate cooling process was included in the CVD process; this process affected the isothermal graphene growth, which is explained using a growth model. We mainly studied a graphite film with the thickness of ∼40 nm and the good thickness uniformity was characterized by atomic force microscopy (AFM), Raman spectroscopy and extreme ultraviolet (EUV) mapping. The graphite formed on the Ni grain boundary was analyzed by transmission electron microscopy (TEM). The relationships between the thickness, optical and electrical properties of the NGF and growth temperature were also studied. [ABSTRACT FROM AUTHOR]

[Display omitted] • AChE-responsive optical and electrochemical sensor designed from PDA@dsPD-Hydrogel. • Electronic/optical property controlled by cleavage of diselenide bond of polymer dot. • Electron-responsive by pressure and strain force influenced by the presence of AChE. • Altered electronic and optical sensor changed by the expressed AChE in PC-12 cells. • AChE activity and inhibition on PC-12 cells monitored through a wireless electronic device. In this study, we produced a stimuli-responsive electrochemical and fluorescence biosensor using carbonized diselenide-crosslinked polymer dot-loaded polydopamine nanoparticles (PDA@dsPD) incorporated into polyvinyl alcohol/chitosan hydrogel, to examine the activity and inhibition of acetylcholinesterase (AChE). The PDA@dsPD inside the hydrogels (i.e., PDA@dsPD-Hydrogel) was sensitive to AChE in the presence of acetylthiocholine, which formed thiocholine that dissolved the diselenide bonds and simultaneously released polydopamine nanoparticles; this affected the optical and electronic performance of the hydrogel. The electronic response-based pressure and strain on the PDA@dsPD-Hydrogel shifted to 23 % when the AChE concentration was 300 U/L, while in the absence of AChE, this value shifted to 46 %. The PDA@dsPD-Hydrogels were able to visualize the AChE fluorescence signal expressed by PC-12 cells, in addition to an increase in electronic conductivity after the cleavage of the diselenide bond. In contrast, no change in the electrochemical or fluorescence signals was observed in the presence of neostigmine, an AChE inhibitor. The novel PDA@dsPD-Hydrogel can even be connected to a wireless electronic device to facilitate the detection of AChE via smartphones. [ABSTRACT FROM AUTHOR]

Cobalt is an essential heavy metal that is necessary for the formation of vitamin B12 (hydroxocobalamin). However, exposure to excess cobalt for a prolonged period can harm the human body, causing pulmonary fibrosis, blindness, deafness, and peripheral neuropathy. 3-Aminotriazole (3-AT) is a catalase inhibitor that is often used to investigate the physiological effects of catalase. The present study found that injection of 3-AT in mice significantly reduced CoCl-induced hearing impairment. In cultured organ of Corti explants from rats, 3-AT treatment protected hair cells from CoCl-induced cytotoxicity. To determine the mechanism by which 3-AT protected from CoCl-induced ototoxicity, we used the HEI-OC1 auditory cell line. Pretreatment with 10 mM 3-AT attenuated CoCl-induced accumulation of ROS and induction of proinflammatory cytokine expression. Interestingly, these protective effects of 3-AT did not require catalase activity, as demonstrated by a series of experiments using RNA interference-mediated catalase knockdown in HEI-OC1 cells and using catalase-deficient mouse embryonic fibroblasts. Our results demonstrated the mechanisms of CoCl-induced ototoxicity that may provide better ways to prevent the ototoxic effect of cobalt exposure. [ABSTRACT FROM AUTHOR]

Resin-bound amines 1a-e condense with isothiocyanates to give thiourea resins 2a-i. Resins 2a-g subsequently react with iodomethane followed by cleavage affording S-methyl isothioureas 4a-g, and resins 2a-b,h-i react with acyl chlorides to afford N-acylated thioureas 6a-d. N-Acylthioureas 8a-f (R(2) = H) were prepared directly from resin-bound amines 1a-d with acyl isothiocyanates. N-Acylthioureas 8a-d,f(R(2) = H) were used for the preparation of S-methyl-N-acylisothioureas 10a-e. Alkylation was performed using methyl iodide. Resin-bound S-methyl-N-acylisothioureas 10a,b,d are converted by an action of hydrazines into 3-amino-1,2,4-triazoles 13a-d. Condensation of resins 8a-e (R(2) = H) with 2-bromoacetophenones in the presence of TEA affords thiazoles 15 a-e. All transformations proceeded in high yields and gave products of good purities. [ABSTRACT FROM AUTHOR]

Grade 3/4 anaemia, which is mainly induced by carboplatin, frequently occurs in patients treated with neoadjuvant docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP). However, dose reduction of carboplatin may raise concerns about the oncological outcome. This study investigated the pathologic complete response (pCR) rate, occurrence of grade 3/4 anaemia, and transfusion rate according to carboplatin dose in patients treated with neoadjuvant TCHP. We retrospectively analysed 294 patients treated with neoadjuvant TCHP between April 2015 and December 2020. Case matching was performed using propensity score matching. Among patients treated with neoadjuvant TCHP, carboplatin area under the plasma concentration–time curve 6 (AUC6) was used in 234 patients (79.6%) and upfront carboplatin AUC5 was used in 60 patients (20.4%). No significant difference in pCR rate was found between the two groups (AUC6: 70.9%, AUC5: 80.0%). In both oestrogen receptor‐positive (ER+) and ER‐ patients, no significant differences were observed between the AUC6 and AUC5 groups (ER+: 54.3% vs. 50.0%, ER‐: 81.7% vs. 86.0%). The case‐matched cohort showed consistent findings. The AUC5 group had lower frequencies of grade 3/4 anaemia (18.3% vs. 34.2%) and transfusion events (10.0% vs. 21.8%) than the AUC6 group. Compared with AUC5, carboplatin at AUC6 would associate with a 2.7‐fold increased risk of grade 3 or 4 chemotherapy‐induced anaemia. Carboplatin AUC5 has comparable cytotoxic effects to carboplatin AUC6 in patients with HER2+ breast cancer treated with six cycles of neoadjuvant TCHP, with fewer complications associated with clinically meaningful anaemia. AUC5 may be the optimal carboplatin dose to reduce TCHP‐induced anaemia in patients with HER2+ breast cancer treated with TCHP. [ABSTRACT FROM AUTHOR]

Abstract: Fractional precipitation based on the difference in solubility of crude paclitaxel dissolved in methanol, to which distilled water must be added, is the most effective method for the pre-purification of paclitaxel. In this study, the effect of the distilled water feeding and mixing method on the efficiency of fractional precipitation and the formation of paclitaxel precipitate were evaluated. When the distilled water was added all at once, the highest purity (∼57.0%) and yield (∼81.0%) were obtained, and a spherical precipitate was formed by the clustering of crystal branches. On the other hand, when the distilled water was added intermittently in several aliquots, the purity and yield tended to decrease with increasing number of additions, and the precipitate took the form of a cross or pentagon with less clustering of branches. Not mixing after the addition of distilled water resulted in high purity (∼57.0%) and the formation of a spherical precipitate that showed increased branching around the nucleus over time. In contrast, when the sample was mixed intermittently after adding distilled water, paclitaxel was obtained in high yield (∼99.7%). Continuously mixing the sample after adding distilled water, however, caused the precipitate crystals to be broken into smaller pieces. [Copyright &y& Elsevier]

[Display omitted] • The self-powered hydrogel sensor controlled by NIR/pH-responsive polymer dot. • Amplified stretchability, conductivity, capacitance achieved after healing by tuning of pH. • The reusable sensor shows repeatability of 12,000 cycles over two cutting-healing process. • Wireless sensor can be applied to monitor the pH tuned amplified pressure and strain. • The sensor detects subtle wrist pulse to rough finger motion without external power. A self-repairable and reusable self-powered electronic skin sensor is developed from NIR/pH-responsive polymer dot (PD) embedded hydrogel with amplified mechanical and electrochemical properties after self-healing. The pH/NIR-controlled mechanical, electrochemical and self-healing performance of the designed hydrogel is achieved by manipulating the hydrogen bond formation with tunable mobility from the PD components. The hydrogel formed at pH 7.4, after treatment with pH 10 and NIR-driven healing, the mechanical stretchability (585%), conductivity (6.8 mS cm−1), capacitance (184.2 mF cm−2), and gauge factor (1.09) was increased by 125%, 4.9 times, 37%, and 72%, respectively. Further, the hydrogel system was explored as a reusable physiological strain sensor which showed excellent strain sensitivity of 0.36 kPa−1 with remarkable repeatability of 12,000 stretching-bending operations over two cutting-healing cycles. The real-time pH/NIR-dependent amplified sensing performance is effectively monitored remotely by using a wireless connection via a smartphone. Additionally, the hydrogel-based supercapacitor was attached with a solar cell for a self-powered body sensor that works seamlessly under sunlight. The integrated system obtains enhanced energy storage upon healing, reaching an overall power conversion efficiency of 2.32%. The NIR/pH-driven durability, the reproducible amplified mechanical and electrical performance of the self-powered electronic skin can be efficiently used for detecting movements ranging from a subtle human wrist pulse to rough finger motions presenting their potential application in wearable human-health monitoring systems. [ABSTRACT FROM AUTHOR]

[Display omitted] • ROS-responsive sensor for selective and sensitive electrochemical cancer sensing. • Tuning surface morphology and induced electron transfer by the cleavage of diselenide-bonds. • Selectivity of sensor shown in vitro diagnosis with ratio of normal and cancer cells. • Electronic/optical property of sensor was change by cellular microenvironment. • Sensor performed real-time and rapid detection by connecting the wireless system. Reactive oxygen species (ROS)-responsive materials for the selective and sensitive electrochemical detection of cancer cells have been studied comprehensively, especially owing to the variable concentration of H 2 O 2 in normal and tumor cells. In this report, we develop a real-time electrochemical sensor based on diselenide-functionalized dopamine-conjugated hyaluronic acid polymer dots (PD(HA/DP)-DiSe) nanoparticles coated on a substrate that could be used for selective tumor diagnosis by tuning the coated surface morphology. The hyaluronic acid-based cancer cell-targeted PD(HA/DP)-DiSe-coated surface demonstrates selectivity and sensitivity toward ROS because of the change in the optical fluorescence after treatment. Owing to cleavage of the Se-Se bond and the formation -Se-OH/-Se-OOH, the PD(HA/DP)-DiSe coated-surface is tuned from a sphere-like to a sheet-like form with smaller size changing the electronic impedance of the sensor. A real-time in vitro selective diagnosis conducts by connecting the sensor to the wireless system and produces an accurate result to distinguish different ratios of MDCK:MDA-MB-231 and MDCK:HeLa cells. Finally, the developed ROS-responsive sensor could specifically differentiate the cancer microenvironment, which is helpful for advanced and selective biomedical purposes. [ABSTRACT FROM AUTHOR]

Cellular senescence is caused by a wide range of intracellular and extracellular stimuli and influences physiological functions, leading to the progression of age-related diseases. Many studies have shown that cellular senescence is related to phosphatase and tension homolog deleted on chromosome ten (PTEN) loss and mammalian target of rapamycin (mTOR) activation. Although it has been reported that mTOR complex 1 (mTORC1) is major anti-aging target in several cell types, the functions and mechanisms of mTOR complex 2 (mTORC2) during aging have not been elucidated in vascular smooth muscle cells (VSMCs). Therefore, the aim of this study was to reveal the relationship between PTEN and mTORC2 during VSMC senescence. We found adriamycin-induced VSMC senescence was accompanied by reduced PTEN protein expression and upregulation of the mTORC2-Akt (Ser 473) pathway and that fisetin treatment reduced VSMC senescence by increasing PTEN and decreasing mTORC2 protein levels. Furthermore, PTEN played a primary role in the anti-aging effect of fisetin, and fisetin-activated PTEN directly regulated the mTORC2-Akt (Ser 473) signaling pathway, and attenuated senescence phenotypes such as senescence-associated β-galactosidase (SA-β-gal) and the p53-p21 signaling pathway in VSMCs. In mouse aortas, fisetin delayed aging by regulating the PTEN-mTORC2-Akt (Ser473) signaling pathway. These results suggest PTEN and mTORC2 are associated with cellular senescence in VSMCs and that the mTORC2-Akt (Ser 473) signaling pathway be considered a new target for preventing senescence-related diseases. • Adriamycin-induced VSMC senescence was accompanied by reduced PTEN expression and upregulation of the mTORC2-Akt pathway. • Fisetin dose-dependently increased PTEN expression and reduced the expressions of mTORC2 and p-Akt (Ser473). • PTEN inhibition by bpV (pic) or siRNA abolished the inhibitory effect of fisetin on the mTORC2-Akt pathway. • Adriamycin treatment did not alter the mTORC2-Akt (Ser473) signaling pathway in PTEN-overexpressed cells. • Fisetin-activated PTEN directly regulates the mTORC2-Akt pathway, leading to inhibition of VSMC senescence. [ABSTRACT FROM AUTHOR]

Skin aging is a complex process and involves extrinsic and intrinsic processes with distinct characteristics. Understanding skin aging requires knowledge of the senescence of human dermal fibroblasts (HDFs) and the biological mechanisms involved in this process. However, the molecular mechanism responsible for the aging of HDFs is still not clear. Therefore, we investigated mechanisms of autophagy, inflammation, and cellular senescence by Western blotting, immunofluorescence, real-time PCR, and senescence-associated β-galactosidase (SA-β-gal) staining in senescent HDFs. We found SRT1720 inhibited the inductions of inflammatory cytokines and cellular senescence by deacetylating acetyl-NF-κB levels and enhancing levels of autophagy-associated proteins and SIRT1 in senescent HDFs. However, the NF-κB activator prostratin attenuated signals associated with autophagy, such as those of LC3-II and Beclin-1, but increased inflammatory cytokine levels and cellular senescence. Notably, the expression levels of SIRT1 and autophagy-associated proteins were higher in aged mice administered SRT1720 than in old mice, and SRT1720 also decreased levels of acetyl-NF-κB, inflammatory cytokines, and senescence markers, which was in accord with in vitro results. These findings support that SRT1720 acts as an anti-aging agent and inhibits the inductions of inflammatory cytokines and senescence by regulating the SIRT1/acetyl-NF-κB signaling pathway and activating autophagy in senescent HDFs. • SIRT1 attenuated inflammatory cytokine induction and cellular senescence in human dermal fibroblasts (HDFs). • SRT1720 increased SIRT1 expression and autophagy. • SIRT1 decreased the expressions of acetyl-NF-κB, IL-6, IL-8, p53, and p21. • Autophagic activation was regulated by the NF-kB pathway in senescent HDFs. • SIRT1 expression by SRT1720 reduced skin inflammation and cellular senescence in an aged mouse model. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the differences in characteristics, clinical stages, treatment modalities, and survival outcomes in patients with non‐small‐cell lung cancer (NSCLC) based on sex differences using Korean nationwide registry data. Methods: We analyzed the data of 8650 patients diagnosed with NSCLC between 2014 and 2017, obtained from the Korean Association for Lung Cancer Registry (KALC‐R). The Cox proportional hazard model was used to define the differences in survival based on sex. Propensity score matching was used to adjust for differences between men and women. Results: Of a total of 10 943 patients, 8650 (79.1%) were diagnosed with NSCLC, of whom 68.7% were men and 31.3% were women. For NSCLC, the median age was higher (69.0 vs. 67.0, p < 0.001) and the proportion of ever‐smokers (84.5% vs. 10.8%, p < 0.001) was higher in men. Adenocarcinoma (55.5% vs. 90.4%, p < 0.001) and stage I NSCLC (26.3% vs. 41.3%, p < 0.001) were more common in women. Survival was significantly lower in men with NSCLC (hazard ratio [HR] 1.493 [95% confidence interval, CI 1.238–1.800], p < 0.001) even after adjusting for meaningful clinical variables, and in the matched cohort (HR 1.339 [1.075–1.667], p = 0.009). Similarly, survival was significantly lower in men with stage IV adenocarcinoma after adjusting for other clinical variables (HR 1.493 [1.238–1.800], p < 0.001) and in the matched cohort (HR 1.339 [1.075–1.667]; p = 0.009). Conclusions: Male patients with NSCLC had poorer prognosis, not only after variable adjustments for prognostic factors, but also in the matched cohort. [ABSTRACT FROM AUTHOR]

• Wireless coated CsWO 3 -FCD sensor provides sensitive bacteria detection. • Conductivity/photoluminescence was changed by interaction of CsWO 3 -FCD and bacteria. • Electrochemical approach has lower LOD towards bacteria than colorimetric method. • Real-time wireless bacteria detection of CsWO 3 -FCD sensor is obtained via smartphone. • CsWO 3 -FCD sensor exhibited excellent antibacterial activity under NIR exposure. Simple and rapid simultaneous detection and killing of bacteria is crucial for addressing health issues related to pathogenic bacteria. Here, we describe the design of a wireless electrochemical and luminescent sensor for bacteria detection using surface-coatable electrochemically generated fluorescent carbon dots (FCDs), which were synthesized from a cationic polymer. The FCDs were further integrated with near-infrared (NIR)-responsive cesium tungsten oxide (CsWO 3) by utilizing catechol moieties on the FCD surface for photothermal-based antibacterial activity. The CsWO 3 –FCD nanohybrids showed strong fluorescence emission, which was quenched due to interaction between the cationic FCD surface and the anionic bacterial cell wall. This interaction could also be observed electrochemically according to the change in resistance values before and after binding with bacteria. In this study, the limit of detection (LOD) was determined at 70 CFU/mL for Escherichia coli and 131 CFU/mL for Staphylococcus aureus using the luminescent method and <10 CFU/mL for both bacterial strains using the electrochemical method, indicating the electrochemical approach as the more sensitive method. Additionally, the electrochemical-based bacterial detection assay can be developed into a wireless bacteria-sensing system, which can be easily monitored in real-time via a smartphone. Furthermore, this nanohybrid was able to cause photothermolysis of bacteria upon NIR exposure owing to the photothermal conversion of CsWO 3 , which killed almost 100% of E. coli and S. aureus using only 1 mg/mL of CsWO 3 –FCD. Thus, this nanohybrid offers a novel approach for dual electrochemical- and luminescent-based detection of bacteria along with high antibacterial activity. [ABSTRACT FROM AUTHOR]

• Thermoacoustic instability, originated from a flame oscillation being followed by a flow instability, is a new finding. • The differences between two distinct noisy flames are analyzed and discussed. • The Strouhal number for oscillatory flame-flow interaction decreases with Reynolds number while it increases (decreases) with equivalence ratio in regime II-1 (II-2). Such an oscillatory behavior is quite different from those in known jet-flow instability results. Experiments on combustion instabilities via flame-flow interaction (thereby thermoacoustic instabilities) were conducted for syngas-air premixed impinging jet flames with the mixing ratio of 10% H 2 and 90% CO in volume, by varying equivalence ratio ϕ and Reynolds number Re D. A flame stability map with a functional dependency on ϕ and Re D was presented. Such flame behaviors were classified into four regimes: attached flame, lifted flame, flash-back, and blow-out. Lifted flame was also divided into two sub-regimes: silent flame (SF, regime I) and noisy flame (NF, regime II). NF are again divided into two sub-regimes: II-1 and II-2. The present main concerns focused on combustion instabilities via flame-flow interaction accompanied by two types of noises. When the cold jet is ignited in regime II-1, the flame oscillation was first started, subsequently being followed by jet-flow instability. While in regime II-2, both the flame and flow oscillations were simultaneously started. The noisy flame in regime II-1 exhibited a strong flame-flow interaction. While that in regime II-2 was identified to a relatively weak interaction of flow instability with the oscillating flame. Both noise level and oscillatory flame-flow interaction could be characterized by functional dependencies on Reynolds number and equivalence ratio, respectively. Both noise levels in regimes I and II increase with Reynolds number and equivalence ratio. Differently from well-known jet-flow instability results showing that Strouhal number is proportional to Re D 1 / 2 , the Strouhal number for oscillatory flame-flow interaction decreases with Reynolds number while it increases (decreases) with equivalence ratio in regime II-1 (II-2). [ABSTRACT FROM AUTHOR]

Herein, we describe the fabrication and characterization of carbonized disulfide core-crosslinked polymer dots with pH-cleavable colorimetric nanosensors, based on diol dye-conjugated fluorescent polymer dots (L-PD), for reduction-triggered paclitaxel (PTX) release during fluorescence imaging-guided chemotherapy of tumors. L-PD were loaded with PTX (PTX loaded L-PD), via π–π stackings or hydrophobic interactions, for selective theragnosis by enhanced release of PTX after the cleavage of disulfide bonds by high concentration of glutathione (GSH) in a tumor. The nano-hybrid system showed fluorescence quenching behavior with less than 2% of PTX released under physiological conditions. However, in a tumor microenvironment, the fluorescence recovered at an acidic-pH, and PTX (approximately 100% of the drug release) was released efficiently out of the matrix by reduction caused by the GSH level in the tumor cells, which improved the effectiveness of the cancer treatment. Therefore, the colorimetric nanosensor showed promising potential in distinguishing between normal and cancerous tissues depending on the surrounding pH and GSH concentrations so that PTX can be selectively delivered into cancer cells for improved cancer diagnosis and chemotherapy. [ABSTRACT FROM AUTHOR]

The most effective agent for the third-line treatment of advanced/metastatic gastric cancer (AGC) has not yet been determined. The aim of this network meta-analysis is to compare the relative efficacy and tolerability of third-line treatments for AGC. We conducted a comprehensive literature review of randomised clinical trials (RCTs) using four electronic databases. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse events (AEs) were used as efficacy or tolerability outcomes. A Bayesian network meta-analysis with a random-effects model was used. Seven RCTs involving 2601 patients and nine treatments were included. The results suggested that 1 mg/kg nivolumab (nivolumab1) + 3 mg/kg ipilimumab (ipilimumab3) (hazard ratio [HR] 0.59, 95% credible interval [Crl] 0.38–0.91) was the most effective treatment, followed by nivolumab (HR 0.63, 95% Crl 0.50–0.79), for prolonging OS. Regorafenib (HR 0.40, 95% Crl 0.28–0.58) was most likely to improve PFS, followed by apatinib (HR 0.45, 95% Crl 0.33–0.60). Nivolumab1 + ipilimumab3 and nivolumab were better at improving ORR, whereas nivolumab1 + ipilimumab3 had the highest toxicity based on the AEs. For benefit-risk ratio, nivolumab, apatinib or regorafenib appeared to be the best options. Chemotherapy or two different dose combinations of nivolumab and ipilimumab were ranked as the next options because of poor tolerability, despite good efficacy. Immunotherapy (nivolumab) or antiangiogenic agents (regorafenib and apatinib) are associated with benefits for benefit-risk ratio as third-line monotherapy. This study might serve as a guideline to aid in the selection of third-line treatments for AGC. • The most effective third-line treatment of advanced gastric cancer is still unresolved. • The aim was to compare the efficacy and tolerability of third-line treatments. • Systematic review and network meta-analysis were performed including nine treatments. • Nivolumab1 plus ipilimumab3 was the most preferable treatment for overall survival. • Regorafenib was the most effective treatment for improving progression free survival. • The findings showed a beneficial effect of immunotherapy and antiangiogenic agents. [ABSTRACT FROM AUTHOR]

Poly (ADP-ribose) polymerase (PARP) inhibitors are effective against BRCA1/2-mutated cancers through synthetic lethality. Unfortunately, most cases ultimately develop acquired resistance. Therefore, enhancing PARP inhibitor sensitivity and preventing resistance in those cells are an unmet clinical need. Here, we investigated the ability of paraspeckle component 1 (PSPC1), as an additional synthetic lethal partner with BRCA1/2, to enhance olaparib sensitivity in preclinical models of BRCA1/2-mutated breast and ovarian cancers. In vitro, the combined olaparib and PSPC1 small interfering RNA (siRNA) exhibited synergistic anti-proliferative activity in BRCA1/2-mutated breast and ovarian cancer cells. The combination therapy also demonstrated synergistic tumor inhibition in a xenograft mouse model. Mechanistically, olaparib monotherapy increased the expressions of p-ATM and DNA-PKcs, suggesting the activation of a DNA repair pathway, whereas combining PSPC1 siRNA with olaparib decreased the expressions of p-ATM and DNA-PKcs again. As such, the combination increased the formation of γH2AX foci, indicating stronger DNA double-strand breaks. Subsequently, these DNA-damaged cells escaped G2/M checkpoint activation, as indicated by the suppression of p-cdc25C (Ser216) and p-cdc2 (Tyr15) after combination treatment. Finally, these cells entered mitosis, which induced increased apoptosis. Thus, this proves that PSPC1 inhibition enhances olaparib sensitivity by targeting DNA damage response in our preclinical model. The combination of olaparib and PSPC1 inhibition merits further clinical investigation to enhance PARP inhibitor efficacy. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the global leading cancer burden in women and the hormone receptor-positive (HR+) subtype is a major part of breast cancer. Though cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are highly effective therapy for HR+ subtype, acquired resistance is inevitable in most cases. Herein, we investigated the paternally expressed gene 10 (PEG10)-associated mechanism of acquired resistance to CDK4/6 inhibitors. Methods: Palbociclib-resistant cells were generated by exposing human HR+ breast cancer cell lines to palbociclib for 7–9 months. In vitro mechanistic study and in vivo xenograft assay were performed. For clinical relevance, public mRNA microarray data sets of early breast cancer were analyzed and PEG10 immunohistochemical staining was performed using pre-CDK4/6 inhibitor tumor samples. Results: We observed that PEG10 was significantly upregulated in palbociclib-resistant cells. Ectopic overexpression of PEG10 in parental cells caused CDK4/6 inhibitor resistance and enhanced epithelial–mesenchymal transition (EMT). On the contrary, PEG10-targeting siRNA or antisense oligonucleotides (ASOs) combined with palbociclib synergistically inhibited proliferation of palbociclib-resistant cells and growth of palbociclib-resistant xenograft in mice and suppressed EMT as well. The mechanistic study confirmed that high PEG10 expression suppressed p21, a natural CDK inhibitor, and SIAH1, a post-translational degrader of ZEB1, augmenting CDK4/6 inhibitor resistance. Then PEG10 siRNA combined with palbociclib suppressed cell cycle progression and EMT via activating p21 and SIAH1, respectively. Consequently, combined PEG10 inhibition and palbociclib overcame CDK4/6 inhibitor resistance. Furthermore, high PEG10 expression was significantly associated with a shorter recurrence-free survival (RFS) based on public mRNA expression data. In pre-CDK4/6 inhibitor treatment tissues, PEG10 positivity by IHC also showed a trend toward a shorter progression-free survival (PFS) with CDK4/6 inhibitor. These results support clinical relevance of PEG10 as a therapeutic target. Conclusions: We demonstrated a novel PEG10-associated mechanism of CDK4/6 inhibitor resistance. We propose PEG10 as a promising therapeutic target for overcoming PEG10-associated resistance to CDK4/6 inhibitors. [ABSTRACT FROM AUTHOR]

Hair dyeing has become a prevalent lifestyle trend, especially within the fashion industry. However, it possesses disadvantages, such as containing carcinogenic and toxic materials. In this study, we developed a biocompatible hair-dyeing technology using a shampoo with a dark polyphenol complex (DPC), referred to as S-DPC. The DPC was formed from a mixture of gallic acid and [1,1′-biphenyl]-2,2′,4,4′,5,5′-hexol and used to enhance both the stability of the hair coating and its ability to scavenge reactive oxygen species (ROS). Colloidal DPC particles play a pivotal role in the coating process of various hair dyes, ensuring the uniform coloring of human hair through intermolecular interactions such as hydrogen bonding. Owing to the effect of a polyphenol complex on hair coating, we observed improved antistatic performance and enhanced mechanical strength, resulting in a substantial increase in elongation at the breaking point from 33.74% to 48.85%. The multicolor S-DPC exhibited antioxidant properties, as indicated by its ROS-scavenging ability, including 2,2-diphenyl-1-picrylhydrazyl inhibition (87–89%), superoxide radical scavenging (84–87%), and hydroxyl radical scavenging (95–98%). Moreover, the in vitro analysis of the DPC revealed nearly 100% cell viability in live and dead assays, highlighting the remarkable biocompatibility of the DPC. Therefore, considering its effectiveness and safety, this biomaterial has considerable potential for applications in hair dyeing. [ABSTRACT FROM AUTHOR]

Simple Summary: Paclitaxel-based chemotherapy is the standard front-line therapy for advanced or metastatic endometrial cancer. However, paclitaxel resistance eternally develops. Based on the high prevalence of PIK3CA mutation, reaching 50%, in endometrial cancer, we preclinically investigated the effectiveness of a combination of a PI3K inhibitor with eribulin, a post-paclitaxel therapy for breast cancer, in treating paclitaxel-resistant, PIK3CA-mutated endometrial cancer. Based on our in vitro and in vivo results, we suggest that paclitaxel resistance is associated with the activation of the PIK3/AKT pathway in PIK3CA-mutated endometrial cancer, and the combination of a PI3K inhibitor and eribulin merits further clinical investigation. Endometrial cancer stands as the predominant gynecological malignancy in developed nations. For advanced or recurrent disease, paclitaxel-based chemotherapy is the standard front-line therapy. However, paclitaxel resistance eternally develops. Based on the high prevalence of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation, reaching 50%, in endometrial cancer, we preclinically investigated the effectiveness of a combination of a phosphatidylinositol 3-kinase (PI3K) inhibitor with eribulin, a post-paclitaxel therapy for breast cancer, in treating paclitaxel-resistant, PIK3CA-mutated endometrial cancer. We generated paclitaxel-resistant cell lines from PIK3CA-mutated endometrial cancer cell lines by gradually increasing the concentration of paclitaxel in cell cultures. We observed that the PI3K/AKT and epithelial–mesenchymal transition (EMT) pathways in paclitaxel-resistant cells were significantly upregulated compared with those in parental cells. Then, we demonstrated that the combination of alpelisib (a PI3K inhibitor) and eribulin more effectively suppressed the cellular growth of paclitaxel-resistant cells in in vitro and in vivo xenograft models. Mechanistically, we demonstrated that the effect of the combination could be enhanced by inhibiting both the PI3K/AKT and EMT pathways. Therefore, we suggest that paclitaxel resistance is associated with the activation of the PIK3/AKT pathway in PIK3CA-mutated endometrial cancer, and the combination of a PI3K inhibitor and eribulin merits further clinical investigation. [ABSTRACT FROM AUTHOR]

Background Low-pass whole-genome sequencing (LP-WGS)–based circulating tumor DNA (ctDNA) analysis is a versatile tool for somatic copy number aberration (CNA) detection, and this study aims to explore its clinical implication in breast cancer. Methods We analyzed LP-WGS ctDNA data from 207 metastatic breast cancer (MBC) patients to explore prognostic value of ctDNA CNA burden and validated it in 465 stage II-III triple-negative breast cancer (TNBC) patients who received neoadjuvant chemotherapy in phase III PEARLY trial (NCT02441933). The clinical implication of locus level LP-WGS ctDNA profiling was further evaluated. Results We found that a high baseline ctDNA CNA burden predicts poor overall survival and progression-free survival of MBC patients. The post hoc analysis of the PEARLY trial showed that a high baseline ctDNA CNA burden predicted poor disease-free survival independent from pathologic complete response (pCR), validating its robust prognostic significance. The 24-month disease-free survival rate was 96.9% and 55.9% in [pCR(+) and low I-score] and [non-pCR and high I-score] patients, respectively. The locus-level ctDNA CNA profile classified MBC patients into 5 molecular clusters and revealed targetable oncogenic CNAs. LP-WGS ctDNA and in vitro analysis identified the BCL6 amplification as a resistance factor for CDK4/6 inhibitors. We estimated ctDNA-based homologous recombination deficiency status of patients by shallowHRD algorithm, which was highest in the TNBC and correlated with platinum-based chemotherapy response. Conclusions These results demonstrate LP-WGS ctDNA CNA analysis as an essential tool for prognosis prediction and molecular profiling. Particularly, ctDNA CNA burden can serve as a useful determinant for escalating or de-escalating (neo)adjuvant strategy in TNBC patients. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to assess post-operative patient subjective satisfaction and to analyze associated peri-operative factors following biplanar medial open wedge high tibial osteotomy (OWHTO).Methods: The study cohort consisted of 88 patients with a minimum of two years of follow-up. Patient satisfaction was evaluated with a questionnaire that assessed (1) overall satisfaction, (2) pain relief, (3) daily living functions, and (4) cosmesis. Patients were categorized into two groups (satisfied or unsatisfied) based on overall satisfaction questionnaire. Pre- and post-operative objective clinical statuses were assessed with a knee scoring system based on the American Knee Society (AKS), the Western Ontario McMaster University Osteoarthritis Index (WOMAC), and range of motion.Results: Of the 88 patients, 85.2% were graded as satisfied according to the overall satisfaction estimation. The percentage of patients satisfied with pain relief, daily living functions, and cosmesis were 85.2%, 86.4%, and 86.4%, respectively. Multivariable logistic regression analysis demonstrated that pre-operative Hip-Knee-Ankle angle (HKAA) (odds ratio (OR) = 1.812), post-operative AKS knee score (OR = 1.156), and post-operative HKAA (OR = 0.717) were significantly associated with overall satisfaction. Pre-operative HKAA (OR = 1.436), post-operative WOMAC activity score (OR = 0.865), and post-operative HKAA (OR = 0.505) were significant predictors for satisfaction with pain reduction, daily living functions, and cosmesis, respectively.Conclusions: Biplanar medial OWHTO is an effective treatment for osteoarthritis with varus deformity in terms of subjective satisfactory outcome. Several factors, including pre- and post-operative HKAA, post-operative AKS and WOMAC score, were significant predictors for subjective satisfaction.Level Of Evidence: Level III. [ABSTRACT FROM AUTHOR]

We developed a Tc-99m and fluorescence-labeled peptide, Tc-99m TAMRA-GHEG-ECG-VAPG to target tumor cells and evaluated the diagnostic performance as a dual-modality imaging agent for tumor in a murine model. TAMRA-GHEG-ECG-VAPG was synthesized by using Fmoc solid-phase peptide synthesis. Radiolabeling of TAMRA-GHEG-ECG-VAPG with Tc-99m was done by using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed in murine models with SW620 tumors. Tumor tissue slides were prepared and analyzed with immunohistochemistry by using confocal microscopy. After radiolabeling procedures with Tc-99m, Tc-99m TAMRA-GHEG-ECG-VAPG complexes were prepared in high yield (>96%). The Kd of Tc-99m TAMRA-GHEG-ECG-VAPG determined by saturation binding was 16.8 ± 3.6 nM. Confocal microscopy images of SW620 cells incubated with TAMRA-GHEG-ECG-VAPG showed strong fluorescence in the cytoplasm. Gamma camera imaging revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-VAPG in tumors. Tumor uptake was effectively blocked by the coinjection of an excess concentration of VAPG. Specific uptake of Tc-99m TAMRA-GHEG-ECG-VAPG was confirmed by biodistribution, ex vivo imaging, and immunohistochemistry stain studies. In vivo and in vitro studies revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-VAPG in tumor cells. Tc-99m TAMRA-GHEG-ECG-VAPG has potential as a dual-modality tumor imaging agent. [ABSTRACT FROM AUTHOR]

We fabricated the large-area (3 × 3 cm 2 ) freestanding nanometer thickness graphite film (NGF) using transfer free process. NGF was grown on Cu foil using CVD and Cu foil is used as the frame of NGF freestanding film. Thickness of the NGF was controlled by gas flow and growth time. Transfer-free process was achieved by selective etching of Cu foil and dipping NGF in alcohol of low surface tension. Freestanding NGF reveals excellent EUV transmittance. This method allowed us to simplify the fabrication process for freestanding film without transfer process and demonstrated a possibility for HVM of pellicle for EUV lithography. [ABSTRACT FROM AUTHOR]

Background: To validate a stratification method using an inverse of treatment decision rules that can classify non-small cell lung cancer (NSCLC) patients in real-world treatment records. Methods: (1) To validate the index classifier against the TNM 7th edition, we analyzed electronic health records of NSCLC patients diagnosed from 2011 to 2015 in a tertiary referral hospital in Seoul, Korea. Predictive accuracy, stage-specific sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and c-statistic were measured. (2) To apply the index classifier in an administrative database, we analyzed NSCLC patients in Korean National Health Insurance Database, 2002–2013. Differential survival rates among the classes were examined with the log-rank test, and class-specific survival rates were compared with the reference survival rates. Results: (1) In the validation study (N = 1375), the overall accuracy was 93.8% (95% CI: 92.5–95.0%). Stage-specific c-statistic was the highest for stage I (0.97, 95% CI: 0.96–0.98) and the lowest for stage III (0.82, 95% CI: 0.77–0.87). (2) In the application study (N = 71,593), the index classifier showed a tendency for differentiating survival probabilities among classes. Compared to the reference TNM survival rates, the index classification under-estimated the survival probability for stages IA, IIIB, and IV, and over-estimated it for stages IIA and IIB. Conclusion: The inverse of the treatment decision rules has a potential to supplement a routinely collected database with information encoded in the treatment decision rules to classify NSCLC patients. It requires further validation and replication in multiple clinical settings. [ABSTRACT FROM AUTHOR]

Simple Summary: Renal cell carcinoma (RCC) is one of the most common types of cancers concerning the kidneys worldwide. Pembrolizumab and axitinib treatment (Pembro/Axi) is amongst the most effective first-line immunotherapies for advanced RCC. However, it remains difficult to predict the effectiveness of Pembro/Axi immunotherapy for the treatment of RCC. Therefore, this prospective study was conducted with the aim of evaluating whether baseline serum interleukin-6 (IL-6) could serve as a predictive biomarker for Pembro/Axi treatment in RCC. Low levels of IL-6 were associated with longer progression-free survival rates, while high IL-6 levels had worse progression-free rates and overall survival. Moreover, high IL-6 levels were related to reduced interferon-γ and tumor necrosis factor-α production. These findings elucidate the clinical and biological implications of IL-6 as a predictive biomarker in RCC patients who received Pembro/Axi as a first-line treatment. Renal cell carcinoma (RCC) is the most common type of kidney malignancy worldwide with Pembrolizumab and axitinib treatment (Pembro/Axi) amongst the most effective first-line immunotherapies for advanced RCC. However, it remains difficult to predict treatment response and early resistance. Therefore, we evaluated whether baseline serum interleukin-6 (IL-6) could be a predictive biomarker. Between November 2019 and December 2021, 58 patients with advanced RCC were enrolled, administered first-line Pembro/Axi, and baseline blood samples were analyzed using flow cytometry. The mean baseline serum IL-6 concentration was 8.6 pg/mL in responders and 84.1 pg/mL in patients with progressive disease. The IL-6 cut-off value was set at 6.5 pg/mL using time-dependent receiver operating characteristic curves, with 37.9% of patients having high baseline serum IL-6 levels and 62.1% having low levels. Objective response rates were 58.3% and 36.4% in low and high IL-6 groups, respectively. Overall survival and progression-free survival were longer in patients with low IL-6 levels than in those with high levels. High IL-6 levels were related to reduced interferon-γ and tumor necrosis factor-α production from CD8+ T cells. Overall, high baseline serum IL-6 levels were associated with worse survival outcomes and reduced T-cell responses in Pembro/Axi-treated advanced RCC patients. [ABSTRACT FROM AUTHOR]

For valence change memory (VCM)-type synapses, a large number of vacancies help to achieve very linearly changed dynamic range, and also, the low activation energy of vacancies enables low-voltage operation. However, a large number of vacancies increases the current of artificial synapses by acting like dopants, which aggravates low-energy operation and device scalability. Here, mixed-dimensional formamidinium bismuth iodides featuring in-situ formed type-I band structure are reported for the VCM-type synapse. As compared to the pure 2D and 0D phases, the mixed phase increases defect density, which induces a better dynamic range and higher linearity. In addition, the mixed phase decreases conductivity for non-paths despite a large number of defects providing lots of conducting paths. Thus, the mixed phase-based memristor devices exhibit excellent potentiation/depression characteristics with asymmetricity of 3.15, 500 conductance states, a dynamic range of 15, pico ampere-scale current level, and energy consumption per spike of 61.08 aJ. A convolutional neural network (CNN) simulation with the Canadian Institute for Advanced Research-10 (CIFAR-10) dataset is also performed, confirming a maximum recognition rate of approximately 87%. This study is expected to lay the groundwork for future research on organic bismuth halide-based memristor synapses usable for a neuromorphic computing system. [ABSTRACT FROM AUTHOR]

Highlights: [•] A fasting–refeeding high fat diet (HDF) model mimics irregular eating habit. [•] A fasting–refeeding HFD induces liver ballooning injury. [•] A fasting–refeeding HDF process elicits hepatic triglyceride accumulation. [•] Fenofibrate, PPARα ligand, prevents liver damage induced by refeeding HFD. [ABSTRACT FROM AUTHOR]