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[Display omitted] • Different regions of interest were investigated at the cellular scale. • Principal component analysis visualized the physicochemical changes in apple flesh. • Single feature spectral variable to simplify and enhance the model. • Hyperspectral microscope imaging as green solution for assessing apple quality. Hyperspectral microscope imaging (HMI) technique was employed to assess the changes in physicochemical parameters and microstructure of 'Golden Delicious' apples flesh during storage. Four regions of interest (ROIs), including whole-cell ROI, intercellular space ROI, cytoplasm ROI, and cell wall ROI were investigated to assess their relationships with physicochemical parameters. Different ROIs presented similar vibrational profiles, but with slight differences in spectral intensity, especially in the range of 800–1000 nm. Spectral angle mapper (SAM) was applied to the HMI of apple tissues at different storage stages to clearly show the structural changes of parenchyma cells, while principal component analysis (PCA) could highlight the distribution of sugars, water and pigments in apple flesh at the cellular scale. Simultaneously with the degradation of acid-soluble pectin (ASP), middle lamella dissolution and increased intercellular space were observed using SEM and TEM. Single feature variables were used to construct linear models based on pearson correlation analysis, with R2 of 0.96 for moisture at 982 nm, 0.85 for water-soluble pectin (WSP) at 420 nm, 0.82 for L* at 946 nm, 0.77 for soluble solids content (SSC) at 484 nm, and 0.66 for firmness at 490 nm. This work demonstrated the great potential of HMI technology as a fast, accurate and efficient solution for assessing the quality of 'Golden Delicious' apples. [ABSTRACT FROM AUTHOR]

With the advent of an ageing era, the number of elderly patients undergoing knee joint replacement is increasing. Postoperative long-term standardized functional exercise is a focal point and difficulty in the recovery of joint function for patients after knee replacement. Virtual reality (VR) is increasingly considered a potentially effective option that can provide patients with a relaxed and enjoyable exercise method. The primary objective of the scoping review to systematically evaluates the impact of virtual reality (VR) technology the movement and functional recovery, psychological state, pain levels, and quality of life of patients after total knee arthroplasty (TKA). It summarises and synthesises VR's effects and feasibility in TKA rehabilitation training, offering a scientific basis and reference for the professional advancement of orthopaedic practice nurses and future research in this domain. We employed the Joanna Briggs Institute's scoping review guidelines as our methodological framework. The literature search spanned from January 2018 to December 31, 2023, encompassing databases such as PubMed, Web of Science, The Cochrane Library, Embase, CNKI, Wanfang, CQVIP, and the China Biomedical Literature Database. An initial search yielded 2708 articles, with 17 studies meeting the inclusion criteria after stringent screening. The findings indicate that VR equipment primarily comprises VR goggles, handheld controllers, and sensor technology. Interventions typically occurred 3 to 5 times weekly, lasting 20–30 min per session. The principal assessment metrics included pain levels, psychological state, joint function, and quality of life. VR technology proves feasible in the rehabilitation of TKA patients, effectively alleviating pain, enhancing psychological states, and improving joint function and quality of life. However, discrepancies exist regarding VR's effect on bolstering lower limb muscle strength. Future research should focus on evidence-based medical practices, optimising VR intervention strategies, developing customised plans tailored to individual patient differences, and potentially extending intervention durations to amplify VR technology's application effects in TKA patient rehabilitation. [ABSTRACT FROM AUTHOR]

Purpose: Oral and maxillofacial surgeons frequently encounter patients who require extractions following exposure to head and neck radiation, and they must assess the risk of extraction and consider alternatives such as deliberate root retention. The purpose of this study was to determine whether dose volume would be a better predictor for osteoradionecrosis (ORN) than total dose.Methods: This is a retrospective cohort study of patients diagnosed with ORN following head and neck radiation (administered between January 2006 and December 2018) and a comparison group selected based on site and dosage who did not develop ORN. The predictor variables were total radiation dose and mandibular dose volume, and the outcome variable was ORN occurrence. Covariates included age, sex, cancer stage and site, radiation therapy type, smoking status, alcohol use, adjuvant chemotherapy use, medical comorbidities, and concomitant tumor surgery. Logistic regression models were employed and area under receiver operating characteristic curve (AUROC) and model accuracy (Acc) were used to determine the better predictor.Results: A total of 56 patients were included in the study: 27 ORN positive (ORN+) and 29 matched controls who did not develop ORN (ORN-). Most patients were male (76.8%), considered smokers (78.6%), used alcohol (80.4%), were in stage IV (66.1%), received chemotherapy (75.0%), and received intensity modulated radiation therapy radiation (55.4%). The statistical models with V50 Gy (cc) and V65 Gy (cc) dosage variables exhibited greater predictability of ORN occurrence than total dose (AUROC: 0.90 vs 0.76 and model accuracy: 0.82 vs 0.75, respectively).Conclusions: The results suggest that following head and neck radiation, dose volume may be a better predictor of ORN risk than total dose. This finding is significant, both for the oral and maxillofacial surgeon who is preoperatively assessing ORN risk following radiation exposure, and for the radiation oncologist striving to minimize the risk associated with their treatment. [ABSTRACT FROM AUTHOR]

Long-term consumption of a high-fat diet (HFD) disrupts energy homeostasis and leads to weight gain. The fat mass and obesity-associated (FTO) gene has been consistently identified to be associated with HFD-induced obesity. The hypothalamus is crucial for regulating energy balance, and HFD-induced hypothalamic leptin resistance contributes to obesity. FTO, an N6-methyladenosine (m6A) RNA methylation regulator, may be a key mediator of leptin resistance. However, the exact mechanisms remain unclear. Therefore, the present study aims to investigate the association between FTO and leptin resistance. After HFD or standard diet (SD) feeding in male mice for 22 weeks, m6A-sequencing and western blotting assays were used to identify target genes and assess protein level, and molecular interaction changes. CRISPR/Cas9 gene knockout system was employed to investigate the potential function of FTO in leptin resistance and obesity. Our data showed that chemokine (C-X3-C motif) ligand 1 (CX3CL1) was a direct downstream target of FTO-mediated m6A modification. Furthermore, upregulation of FTO/CX3CL1 and suppressor of cytokine signaling 3 (SOCS3) in the hypothalamus impaired leptin-signal transducer and activator of transcription 3 signaling, resulting in leptin resistance and obesity. Compared to wild-type (WT) mice, FTO deficiency in leptin receptor-expressing neurons of the hypothalamus significantly inhibited the upregulation of CX3CL1 and SOCS3, and partially ameliorating leptin resistance under HFD conditions. Our findings reveal that FTO involved in the hypothalamic leptin resistance and provides novel insight into the function of FTO in the contribution to hypothalamic leptin resistance and obesity. [Display omitted] [ABSTRACT FROM AUTHOR]

• A significant proportion of patients with HPV-associated OP-SCCs and IRFs/HRFs following surgery did not receive PORT or POCRT. • Lack of receipt of PORT or POCRT for both IRF and HRFs was associated with inferior OS. • No difference in OS was noted between PORT and POCRT for patients with HRFs. Intermediate and high-risk features (IRFs/HRFs) for locoregional recurrence following initial surgery for oropharyngeal SCCs (OP-SCCs) were defined prior to the known association of HPV with OP-SCC. There are limited reports on practice patterns and outcomes associated with post-operative radiation therapy (PORT) or chemoradiation (POCRT) for HPV-associated OP-SCCs. The National Cancer Database was queried for patients with HPV-associated OP-SCCs managed initially with surgery with IRFs or HRFs. IRFs were defined as pT3/T4 disease, pN1-3 disease, and lymphovascular space invasion, and HRFs as positive margins and extranodal extension (ENE). Patients were stratified into no adjuvant therapy, PORT, or POCRT arms. Kaplan-Meier analysis was utilized for comparison of overall survival (OS) between treatment arms followed by a Cox multivariate (MVA) proportional-hazards model and propensity score analyses with inverse probability treatment weighting (IPTW). We identified 6,301 patients; 51.2% had IRFs only and 48.8% had HRFs. Regarding treatment, 25.5%, 38.2%, and 36.3% of patients received no RT, PORT, and POCRT, respectively. Patients with IRFs who did not receive RT or CRT had inferior 8-year OS (81.1% vs. 87.8%; p < 0.001) that remained significant on IPTW MVA (hazard ratio (HR) = 1.69 (95% CI: 1.27–2.24; p < 0.001). Among patients with HRFs, 8-year OS was not significantly different between patients receiving PORT vs. POCRT (77.3% vs. 79.2%; p = 0.22) that remained insignificant on IPTW MVA (HR = 0.91(0.72–1.17); p = 0.48). A significant proportion of HPV-associated OP-SCC patients with IRFs or HRFs did not receive PORT, which was associated with inferior OS. We did not demonstrate with statistical power that POCRT vs. PORT was associated with superior OS in patients with HRFs, though prospective studies are warranted. [ABSTRACT FROM AUTHOR]

Highlights • Murray's law of tree-like rectangular microchannel network is reexamined. • Effect of dimensional and structural parameters on the Murray's law are investigated. • Convective heat transfer of a tree-like rectangular microchannel heat sink is studied. Abstract The present work theoretically and numerically reexamines the Murray's law to design a tree-like rectangular microchannel network with constant microchannel height under the constraint of constant total channel volume, and investigates effects of the dimensional and structural parameters of the tree-like network on the optimal width ratio and optimal hydraulic diameter ratio of rectangular microchannels at two successive branching levels to achieve a minimum hydraulic resistance. The results show that the optimal hydraulic diameter ratio of the tree-like rectangular microchannel network does not follow the conventional Murray's law. Both the optimal width ratio and the optimal hydraulic diameter ratio to achieve a minimum hydraulic resistance strongly depend on the dimensional and structural parameters including rectangular channel height H , total channel volume V , channel length ratio γ , channel length at the initial branching level L 0 , branching number N and branching level m of the tree-like network. Additionally, the present work finds that the average convective heat transfer coefficient of a heat sink with an elementary T-shaped tree-like rectangular liquid-cooling microchannel network with the constant channel height increases with both the increasing width ratio of microchannels at two successive branching levels and the increasing channel height. [ABSTRACT FROM AUTHOR]

Low-temperature thermochronology is used widely in the Tibet plateau uplift. Some researches, however, have defined the time of rapid denudation as simply rock uplift and have neglected the fact that the rock denudation recorded by fission track (FT) data was controlled by both surface incision and rock uplift. The incision of the Yarlung Zangbo River had a significant influence on uplift history inversion in Southern Tibet. This paper simulated the bedrock denudation and river incision histories using apatite fission track (AFT) data sampled from the Gangdese conglomerate belt, which is located in the middle of Southern Tibet, and analyzed the geological meaning of the AFT age of each sample. The results showed the following: (1) In the early Miocene (22–16 Ma), both the value of the denudation rate and the incision rate were high (0.56 mm/yr and 0.24 mm/yr). (2) In the middle-late Miocene, the incision rate (0.12 mm/yr) was similar to the denudation rate (0.09–0.11 mm/yr). (3) The historical model between river incision and bedrock denudation revealed a significant difference in the denudation rate during the period ca. 8–6 Ma. Combining these data with previously published thermochronological ages and synthesizing these ages with regional geological, we arrived at the following conclusions: (1) In the early Miocene, the denudation event probably was caused by a combined result of Indian plate rollback and the incision of the Yarlung Zangbo River. (2) In the middle-late Miocene, the denudation rate was consistent with the incision rate, which suggested that the denudation episode was caused by climate change associated with Asian monsoon intensification. (3) After 8 Ma, the stable and slow incision rate indicated that regional drastic uplift had ceased. The paleo-elevation of the research area had approached, and even exceeded, the present-day elevation in the late Miocene. [ABSTRACT FROM AUTHOR]

Tetracycline (TCN) is a typical antibiotic with ecological toxicity, which is easy to cause bacterial drug resistance. Single-atom catalysts have a broad application prospect in the remediation of antibiotic polluted water by activated persulfate (PDS), but its catalytic properties are limited because of its high surface energy and easy aggregation. Therefore, in our manuscript, a novel nitrogen doped magnetic graphene oxide confined Fe-Co dual single-atom catalyst (Fe/Co(1:1) (S) -NMGO) was prepared by one-step molten salt assisted high temperature pyrolysis. XPS and AC-HAADF-STEM analysis indicated single-atom Fe and Co existed. Fe and Co atoms were bound to the material mainly through coordination with pyridinic N and pyrrolic N. While single-atom Fe and Co were simultaneously introduced into the modified materials, the removal rate of TCN reached 93.1%, implying the significant synergistic effect of single-atom Fe and Co on TCN removal. Molten salt assisted high-temperature pyrolysis significantly improved the TCN degradation rate. In addition, this research showed that the existence of magnetite nanoparticles was beneficial to improve the separation performance of the single-atom catalysts as well as the catalytic performance. At the same time, the effects of some key parameters (Fe/Co molar ratio, catalyst dosage, PDS dosage, initial pH, coexisting anions and humic acids) on TCN degradation in Fe/Co(1:1) (S) -NMGO/PDS system were also investigated. The catalytic potential in actual water and regeneration performance of the material were also evaluated. The possible activation mechanism and degradation pathway of TCN were proposed. These findings will provide important reference for the future design and application of single-atom-involved catalysts. [Display omitted] • Fe/Co dual single-atom catalyst was prepared by molten salt assisted pyrolysis. • Molten salts could provide a high polarity environment to destroy metal-metal bond. • Single Fe and Co atoms anchored on NMGO are verified by AC-HAADF-STEM. • TCN removal rate in this system could reach 93% at low catalyzer and PDS dosage. • Free radical (SO 4 •− >O 2 •− >HO•) oxidation were the main degradation mechanisms. [ABSTRACT FROM AUTHOR]

• Curcumin protected against cachectic weight loss in C26 tumor-bearing mice. • Curcumin alleviated cancer cachexia-associated adipocyte atrophy and lipid degradation. • The protective effects of curcumin on cachectic fat loss are mediated by the cAMP/PKA/CREB signaling pathway. Cachexia is a multifactorial debilitating syndrome that is responsible for 22% of mortality among cancer patients, and there are no effective therapeutic agents available. Curcumin, a polyphenolic compound derived from the plant turmeric, has been shown to have anti-inflammatory, antioxidant, anti-autophagic, and antitumor activities. However, its function in cancer cachexia remains largely unexplored. This study aimed to elucidate the mechanisms by which curcumin improves adipose atrophy in cancer cachexia. C26 tumor-bearing BALB/c mice and β3-adrenoceptor agonist CL316243 stimulated BALB/c mice were used to observe the therapeutic effects of curcumin on the lipid degradation of cancer cachexia in vivo. The effects of curcumin in vitro were examined using mature 3T3-L1 adipocytes treated with a conditioned medium of C26 tumor cells or CL316243. Mice with C26 tumors and cachexia were protected from weight loss and adipose atrophy by curcumin (50 mg/kg, i.g.). Curcumin significantly reduced serum levels of free fatty acids and increased triglyceride levels. In addition, curcumin significantly inhibited PKA and CREB activation in the adipose tissue of cancer cachectic mice. Curcumin also ameliorated CL316243-induced adipose atrophy and inhibited hormone-mediated PKA and CREB activation in mice. Moreover, the lipid droplet degradation induced by C26 tumor cell conditioned medium in mature 3T3-L1 adipocytes was ameliorated by curcumin (20 µM) treatment. Curcumin also improved the lipid droplet degradation of mature 3T3-L1 adipocytes induced by CL316243. Curcumin might be expected to be a therapeutic supplement for cancer cachexia patients, primarily through inhibiting adipose tissue loss via the cAMP/PKA/CREB signaling pathway. [Display omitted]. [ABSTRACT FROM AUTHOR]

Epidemiological studies have indicated that exposure to ambient air-borne fine particulate matter (PM2.5) is associated with many cardiopulmonary diseases; however, the underlying pathological mechanisms of PM2.5-induced lung injury remain unknown. In this study, we aimed to assess the impact of acute or prolonged exposure to water-insoluble fractions of PM2.5 (PM2.5 particulate) on lung injury and its molecular mechanisms. Balb/c mice were randomly exposed to PM2.5 once (acute exposure) or once every three days for a total of 6 times (prolonged exposure). Lung, BALF and blood samples were collected, and pulmonary pathophysiological alterations were analyzed. Nrf2 knockout mice were adapted to assess the involvement of Nrf2 in lung injury, and transcriptomic analysis was performed to delineate the mechanisms. Through transcriptomic analysis and validation of Nrf2 knockout mice, we found that acute exposure to PM2.5 insoluble particulates induced neutrophil infiltration-mediated airway inflammation, whereas prolonged exposure to PM2.5 insoluble particulate triggered lung fibrosis by decreasing the transcriptional activity of Nrf2, which resulted in the downregulated expression of antioxidant-related genes. In response to secondary LPS exposure, prolonged PM2.5 exposure induced more severe lung injury, indicating that prolonged PM2.5 exposure induced Nrf2 inhibition weakened its antioxidative defense capacity against oxidative stress injury, leading to the formation of pulmonary fibrosis and increasing its susceptibility to secondary bacterial infection. [Display omitted] • Acute exposure to PM2.5 induced neutrophil mediated airway inflammation. • Prolonged exposure to PM2.5 induced lung fibrosis. • Reduced antioxidant-related genes expression was found after PM2.5 exposure. • Nrf2 knockout mice exhibit increased pulmonary fibrosis after PM2.5 exposure. • PM2.5 exposure increased the susceptibility for secondary bacterial infection. [ABSTRACT FROM AUTHOR]

Leaf senescence and abscission play crucial role in annual plant adapting to seasonal alteration and climate changes by shortening life cycle and development process in response to abiotic and/or biotic stressors underlying phytohormones and environmental signals. Ethylene and abscisic acid are the major phytohormones that promotes leaf senescence, involving various transcription factors, such as EIN3 (ethylene-insensitive 3) and EIL (ethylene-insensitive 3-like) gene family, controlling leaf senescence through metabolite biosynthesis and signal transduction pathways. However, the roles of EIN3 regulating leaf senescence responding to environmental changes in perennial plant, especially forestry tree, remain unclear. In this study, we found that BpEIN3.1 from a subordinated to EIL3 subclade, is a transcription repressor and regulated light-dependent premature leaf senescence in birch (Betula platyphylla). BpEIN3.1 might inhibits the transcription of BpATPS1 by binding to its promoter. Shading suppressed premature leaf senescence in birch ein3.1 mutant line. Ethylene and abscisic acid biosynthesis were also reduced. In addition, abscisic acid positively regulated the expression of BpEIN3.1. This was demonstrated by the hormone-response element analysis of BpEIN3.1 promoter and its gene expression after the hormone treatments. Moreover, our results showed that abscisic acid is also involved in maintaining homeostasis. The molecular mechanism of leaf senescence provides a possibility to increasing wood production by delaying of leaf senescence. • Function of BpEIN3.1 regulating leaf senescence in Betula platyphylla was analyzed. • BpEIN3.1 served in inhibition of ethylene and abscisic acid biosynthesis, which delayed leaf senescence. • Light affects leaf senescence of plants. [ABSTRACT FROM AUTHOR]

The objective of this work was to investigate the effect of cutting parameters on the cutting performance of sisal leaves under the impact cutting and to obtain the optimal cutting parameters to reduce cutting force and cutting energy. A rotary cutting method for sisal leaves was proposed, and the experimental results showed that cutting parameters had a significant impact on the ultimate shear stress and the specific cutting energy of sisal leaves. Increasing the cutting speed helps to reduce the ultimate shear stress and the specific cutting energy, but the specific cutting energy will increase when the cutting speed is greater than 3 m/s. Meanwhile, under the leaf elevation angle of 45° and the blade oblique angle of 40°, the minimum average ultimate shear stress (7.03 × 10−2 MPa) and minimum specific cutting energy (2.49 × 10−3 J/mm2) were achieved at the cutting speeds of 5 m/s and 3 m/s, respectively. Besides, the lowest cutting cross-section splitting degree was achieved under the blade oblique angle of 40°. The experiment results show that the cutting method proposed in this paper is effective, which provides an important basis for improving the current sisal leaf-cutting device and developing economic sisal leaves harvesting equipment in the future. [Display omitted] • A rotary cutting method was proposed for cutting sisal leaves. • The influence of cutting parameters on the cutting performance was investigated. • The optimal cutting parameter settings were obtained. • Increasing the blade oblique angle can improve the quality of cutting cross-section. [ABSTRACT FROM AUTHOR]

Purpose: To describe a method for streamlining the process of elective nodal volume definition for head-and-neck (H&N) intensity-modulated radiotherapy (IMRT) planning. Methods and Materials: A total of 20 patients who had undergone curative-intent RT for H&N cancer underwent comprehensive treatment planning using three distinct, plan design techniques: conventional three-field design, target-defined IMRT (TD-IMRT), and conformal avoidance IMRT (CA-IMRT). For each patient, the conventional three-field design was created first, thereby providing the “outermost boundaries” for subsequent IMRT design. In brief, TD-IMRT involved physician contouring of the gross tumor volume, high- and low-risk clinical target volume, and normal tissue avoidance structures on consecutive 1.25-mm computed tomography images. CA-IMRT involved physician contouring of the gross tumor volume and normal tissue avoidance structures only. The overall physician time for each approach was monitored, and the resultant plans were rigorously compared. Results: The average physician working time for the design of the respective H&N treatment contours was 0.3 hour for the conventional three-field design plan, 2.7 hours for TD-IMRT, and 0.9 hour for CA-IMRT. Dosimetric analysis confirmed that the largest volume of tissue treated to an intermediate (50 Gy) and high (70 Gy) dose occurred with the conventional three-field design followed by CA-IMRT and then TD-IMRT. However, for the two IMRT approaches, comparable results were found in terms of salivary gland and spinal cord protection. Conclusion: CA-IMRT for H&N treatment offers an alternative to TD-IMRT. The overall time for physician contouring was substantially reduced (approximately threefold), yielding a more standardized elective nodal volume. Because of the complexity of H&N IMRT target design, CA-IMRT might ultimately prove a safer and more reliable method to export to general radiation oncology practitioners, particularly those with limited H&N caseload experience. [Copyright &y& Elsevier]

With the advantages of high efficiency, clean and renewable energy, the technology of sorption/desorption-based atmospheric water harvesting powered by solar energy has gradually attracted the increasing attention of researchers. In this review paper, through analyzing and summarizing the principles, the performance indexes, the measurements of parameters, the material types, the morphology modification, and the system design and devices of this technology, it was found that the existing research mainly focused on adsorbents, while there are still some imperfections, such as limited application circumstances, instability, discontinuous working and long cycle. Accordingly, the direction of future research is expected to redesign adsorbent materials for higher adsorption-desorption rate and wider range of applications, add heat accumulator and air-driving equipment to make system controllable and flexible, miniaturize devices for convenient utilization, and optimize systems to shorten the water collection cycle and to achieve rapid and continuous working. To follow the direction above, there are also some suggestions for adsorbents and system design. • Summarize typical materials and their latest development in the sorption/desorption-based atmospheric water harvesting system. • Generalize and compare the efficiency, used materials, and characteristics of typical atmospheric water harvesting devices. • Point out improvement directions to develop an efficient, economic and environmental atmospheric water harvesting device. [ABSTRACT FROM AUTHOR]

A facile and tunable strategy is proposed to fabricate the Janus porous membrane (JPM) comprising hydrophobic and controlled-hydrophilic wetting surfaces. The control over the wettability of hydrophilic surface is well achieved by tuning the temperature, reaction time, and surface modification. The JPM has directional cross-plane water transport ability, which is demonstrated in water harvest. The prepared JPM exhibits an interesting cross-plane unidirectional selectivity for oil transport at oil-water interface. The synergistic effect developed due to the directional oil transport and charge-screening, which offered an efficient separation of both the heavy oil and light oil from oil-in-water emulsions utilizing large pore size JPM. This easy-to-prepare and tunable strategy endows the JPM with many practical applications that is important for the evolution of JPM from a scientific concept to practical materials in real world. The large pore size JPM with synergistic effect developed due to the directional liquids transport and charge-screening can efficient separate both the heavy oil and light oil from surfactant stabilized oil-in-water emulsions. Image 1 • A facile and tunable strategy to fabricate the JPM with controllable wettability is proposed. • The as-prepared JPM shows intelligent liquids manipulation behavior. • The liquids manipulation property of the JPM is demonstrated in water harvesting. • The large pore size JPM can realize the separation of surfactant stabilized O/W emulsions. [ABSTRACT FROM AUTHOR]

Aims High level of saturated fatty acids leads to mitochondrial dysfunction and inflammation in the development of insulin resistance in skeletal muscle. We recently found that puerarin improved impaired insulin signaling in skeletal muscle in diabetic animals and in myotubes in vitro . However, whether puerarin can act directly on muscle cells to alleviate lipid-induced mitochondrial dysfunction and inflammation remains obscure. This study was conducted to analyze the attributive properties of puerarin against mitochondrial dysfunction and inflammation in skeletal muscle cells with insulin resistance. Main methods The effects of puerarin on mitochondrial biogenesis, oxidative phosphorylation, dynamics of fusion, fission and mitophagy, oxidative stress, as well as inflammatory response and insulin sensitivity in L6 myotubes treated with palmitate were examined. Key findings Puerarin pretreatment improve insulin sensitivity and prevented muscle cells from palmitate-induced mitochondrial dysfunction manifested by the increases of complex I activity, mitochondrial membrane potential and ATP generation, and the decrease of reactive oxygen species (ROS) production. Augmented expression of genes involved in mitochondrial biogenesis, oxidative phosphorylation, and the detoxification of ROS were also observed upon puerarin supplementation. Moreover, puerarin modulated mitochondrial fusion and fission, and rescued palmitate-impaired mitophagy via phosphatase and tensin homolog-induced putative kinase 1(PINK1)/Parkin pathway. In addition, puerarin attenuated palmitate-induced inflammation through the inhibition of toll-like receptor 4/nuclear factor-κB signaling pathway. Significance Our findings indicated that puerarin could act directly on muscle cells to attenuate palmitate-induced mitochondrial dysfunction, impaired mitophagy and inflammatory response, thereby contributing to the improvement of insulin sensitivity. [ABSTRACT FROM AUTHOR]

Neuroinflammation following peripheral surgery is a pivotal pathogenic mechanism of postoperative cognitive dysfunction (POCD). However, the key site of inflammation-mediated neural damage remains unclear. Impaired mitochondrial function is a vital feature of degenerated neurons. Dynamin-related protein 1 (DRP1), a crucial regulator of mitochondrial dynamics, has been shown to play an essential role in synapse formation. Here, we designed experiments to assess whether Drp1-regulated mitochondrial dynamics and function are involved in the pathological processes of POCD and elucidate its relationship with neuroinflammation. Aged mice were subjected to experimental laparotomy under isoflurane anesthesia. Primary neurons and SH-SY5Y cells were exposed to tumor necrosis factor (TNF). We found an increase in Drp1 activation as well as mitochondrial fragmentation both in the hippocampus of mice after surgery and primary neurons after TNF exposure. Pretreatment with Mdivi-1, a Drp1 specific inhibitor, reduced this mitochondrial fragmentation. Drp1 knockdown with small interfering RNA blocked TNF-induced mitochondrial fragmentation in SH-SY5Y cells. However, the application of Mdivi-1 exhibited a negative impact on mitochondrial function and neurite growth in primary neurons. Calcineurin activity was increased in primary neurons after TNF exposure and contributed to the Drp1 activation. The calcineurin inhibitor FK506 exhibited a Drp1-independent function that mitigated mitochondrial dysfunction. Finally, we found that FK506 pretreatment ameliorated the neurite growth in neurons treated with TNF and the learning ability of mice after surgery. Overall, our research indicated a crucial role of mitochondrial function in the pathological processes of POCD, and neuronal metabolic modulation may represent a novel and important target for POCD. [Display omitted] • Drp1-mediated mitochondrial fission involved in the pathological processes of POCD. • Mitochondrial dysfunction occurred prior to fission under TNF stimulation. • Inhibiting fission worsened mitochondrial function and neural outcome. • Calcineurin mediated Drp1 activation in response to TNF stimulation. • Calcineurin inhibition may be a potential therapeutic strategy for POCD. [ABSTRACT FROM AUTHOR]

• Organic carbon and elemental carbon have totally different formation mechanisms. • Increasing oxygen concentration can reduce the emission of carbon components. • The AAE of coal combustion is much smaller than that of atmospheric aerosol. • Coal combustion is significant in light absorption capacity of atmospheric aerosol. Under typical Chinese wintry rural conditions, dominating individual coal heating would emit lots of the fine fraction of ambient aerosol exclusively including carbonaceous particulate matter. In this study, a specified drop tube furnace system is employed to simulate experimentally particle matter emitted during individual coal combustion. Emphatically, the effects of coal types, oxygen concentration and combustion ambient on the formation characteristics of carbonaceous aerosols in the flue gas were discussed. It was found that the fraction of organic carbon (OC) and elemental carbon (EC) in the flue gas produced by bituminous coal combustion was lower than that of lignite. Meanwhile, with the increase of oxygen concentration, the production of OC and EC decreased, but the sensitivity of EC to oxygen concentration was higher than that of OC, which indicated that the formation mechanism of OC and EC is extremely different. Noticeable, the Absorption Ångström Exponent (AAE) of methanol-soluble organic carbon (MSOC) is higher than that of water-soluble organic carbon (WSOC), which indicates that a large amount of methanol-soluble but water-insoluble brown carbon has strong light absorption capacity between 330 nm and 550 nm, and its light absorption capacity tends to be in the short-wave region. The mass absorption efficiency (MAE) of brown carbon produced by coal combustion (0.1–1 m2/gC) is similar to that of atmospheric aerosol (0.3–1.8 m2/gC), which indicates that the contribution of brown carbon emitted from coal combustion to the light absorption capacity of atmospheric aerosol should not be underestimated. [ABSTRACT FROM AUTHOR]

A vertical Silicon Controlled Rectifier (VSCR) realized in a high-voltage (HV) 40 V bipolar process is proposed for electrostatic discharge (ESD) protection applications. In addition, a new method is proposed to alter the layout of the emitter regions of the parasitic vertical PNP (VPNP) bipolar transistor in the VSCR to optimize the trigger voltage and the area of the VSCR. The transmission line pulsing (TLP) measurement results show that the VSCR possesses enhanced ESD robustness compared to the conventional vertical PNP (VPNP) bipolar transistor. The new VSCR can adjust trigger voltage, holding voltage and failure current with changing the number of emitter regions. Compare to VPNP bipolar transistor, the VSCR is more suitable for 40 V bipolar process. [ABSTRACT FROM AUTHOR]

Tropomyosin receptor kinases (TRKs) are a family of TRKA, TRKB and TRKC isoforms. It has been widely reported that TRKs are implicated in a variety of tumors with several Pan -TRK inhibitors currently being used or evaluated in clinical treatment. However, off-target adverse events frequently occur in the clinical use of Pan -TRK inhibitors, which result in poor patient compliance, even drug discontinuation. Although a subtype-selectivity TRK inhibitor may avert the potential off-target adverse events and can act as a more powerful tool compound in the biochemical studies on TRKs, the high sequence similarities of TRKs hinder the development of subtype-selectivity TRK inhibitors. For example, no selective TRKC inhibitor has been reported. Herein, a selective TRKC inhibitor (L13) was disclosed, with potent TRKC inhibitory activity and 107.5-/34.9-fold selectivity over TRKA/B (IC 50 TRKA/B/C = 1400 nM, 454 nM, 13 nM, respectively). Extensive molecular dynamics simulations illustrated that key interactions of L13 with the residues and diversely conserved water molecules in the ribose regions of different TRKs may be the structural basis of selectivity. This will provide inspiring insights into the development of subtype-selectivity TRK inhibitors. Moreover, L13 could serve as a tool compound to investigate the distinct biological functions of TRKC and a starting point for further research on drugs specifically targeting TRKC. [Display omitted] • Off-target adverse events can occur in the use of Pan -TRK inhibitors. • A subtype-selectivity TRK inhibitor may avert off-target adverse events. • A subtype-selective TRKC (L13) inhibitor was disclosed for the first time. • Molecular dynamics simulations illustrated the structural basis of selectivity. [ABSTRACT FROM AUTHOR]

The article presents a study related to activation of psoriform phenotype in mice by Sirtuin 1 (SIRT1) protein. Topics discussed include activities of SIRT 1 like role as a metabolic sensor, development of a psoriatic mouse model, histological analysis of skin cells of mice, analysis of biochemical marker for Ki-67 antigen, reduction in skin lesion after treatment with SIRT1 activator and role of SIRT1 in preventing Aldara-induced psoriasiform lesion in mice.

Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems . Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3 + cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3 + at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk. [ABSTRACT FROM AUTHOR]

Patients with hematologic malignancies were conditioned using a rabbit antithymocyte globulin–based reduced-intensity conditioning regimen for allogeneic stem cell transplantation. Donor-derived CD3+ cell count (ddCD3), a product of CD3+ cell chimerism and absolute CD3+ cell count, when <110/μL at 8 weeks post-stem cell transplantation predicted a high risk of sustained mixed chimerism and relapse. Alternatively, patients with a higher ddCD3 developed graft-versus-host disease more frequently, and when partially chimeric, had higher rates of conversion to full donor chimerism after withdrawal of immunosuppression. Early data from our small cohort of patients indicate that ddCD3 at 8 weeks may be used to guide decisions regarding withdrawal of immunosuppression and administration of donor lymphocyte infusion in partially T cell–depleted reduced-intensity regimens. [Copyright &y& Elsevier]

Air pollutants are important factors that contribute to the development and exacerbation of asthma, but experimental evidence still needs to be collected and the mechanisms still need to be addressed. In this study, we aimed to assess the association between PM2.5 exposure and asthma development. The effects of PM2.5 exposure on the barrier functions of airway epithelial cells were also determined. PM2.5 was collected from Nanjing, China, and its soluble extract was prepared. Human lung epithelial cells (BEAS-2B) were treated with different concentrations of soluble PM2.5 extract, and cell viability was detected by FACS using Annexin V-FITC staining. PM2.5-induced oxidative stress and inflammatory events were assessed by DCF-DA staining and qPCR. PM2.5-induced dysfunction of the airway epithelial barrier was assessed by measuring the expression of tight junction molecules. In vivo, BALB/c mice were treated with OVA in the presence or absence of PM2.5 solution, followed by exposure to OVA aerosols. Allergy-induced airway inflammation and lung injury were assessed by histopathological analyses. Soluble PM2.5 extract exposure in vitro decreased the viability and increased apoptosis of airway epithelial cells. Soluble PM2.5 extract induced oxidative stress and enhanced pro-inflammatory factor expression by activating the NF-κB and MAPK signalling pathways, which were accompanied by reduced airway barrier function. The in vivo data demonstrated that PM2.5 exposure increased the effects of allergy sensitization after respiratory exposure to allergens, which led to the development of asthma. This study suggests that exposure to soluble PM2.5 extract contributes to airway barrier dysfunction. The soluble mediators generated by airway epithelial cells in response to PM2.5 exposure orchestrate the breaking of inhalational tolerance and sensitization to allergic antigens, leading to the exacerbated development of asthma. Unlabelled Image • A method that enables the assessment of the pathological effects of soluble PM2.5 extract on asthma was developed. • Soluble PM2.5 extract impaired airway epithelial morphology and physiology. • Soluble PM2.5 extract disrupted airway mucosal barrier functions. • Soluble PM2.5 extract inhibited immunotolerance and promoted experimental asthma. [ABSTRACT FROM AUTHOR]

Diabetes-induced retinal neurodegeneration occurs before visible microvascular abnormalities. Hyperglycemia-induced endoplasmic reticulum (ER) stress (ERS) and oxidative stress(OS) were considered as the important factors during diabetic retinopathy development. Liraglutide (LIRA), a glucagon-like peptide-1 (GLP-1) analogue, is widely used in the clinic and also proved having protective effect on neurodegenerative diseases. The purpose of this study was to evaluate the neuroprotective effect of LIRA on diabetes-induced retinal neurodegeneration and underlying mechanisms. In vivo , a high-fat diet and streptozotocin (STZ) injection were used inducing diabetes model. Hematoxylin-eosin staining was used for morphological observation and measuring retinal thickness. In vitro , Neuro2a cells were cultured in normal and high-glucose conditions. Flow cytometry was performed to analyze apoptosis. Additionally, Western blotting and Immunohistochemistry were carried out to detect proteins expression. The retinal thickness was decreased in diabetes. However, the retinal thickness reducing was delay after LIRA treatment in diabetes. In vitro , the apoptosis percentage, ROS production and the expression of ERS related protein GRP78, ASK1, p-IRE1α was increased and the expression of Nrf2, p-Erk1/2, Trx was decreased after HG treatment, However, the apoptosis percentage, generation of ROS and the expression of GRP78, ASK1, p-IRE1 were decreased. The expression of Nrf2, p-Erk1/2, Trx was increased significantly after LIRA treatment. Taken together, our results indicated that LIRA can alleviates diabetes-induced retinal neurodegeneration which activated Erk pathway inhibiting OS and regulated the Trx-ASK1complex inhibiting ERS. • Liraglutide has a protective effect on retinal neurodegeneration in diabetes. • Liraglutide can activate ERK pathway decreasing Oxidative Stress. • Liraglutide can regulate Trx-ASK1 complex decreasing Endoplasmic Reticulum Stress. [ABSTRACT FROM AUTHOR]

Brain injury after sepsis leads to high mortality and long-term brain dysfunction in patients. Previous studies revealed that borneol has a protective effect on the brain, but its function on sepsis associated encephalopathy (SAE) remains unknown. Herein, we investigated the protective effect of borneol against sepsis-related brain injury. Lipopolysaccharide (LPS)-induced sepsis mice and cells were treated with borneol at the dose of 100 mg/kg by gavage or 10 μg/ml in culture, respectively. The protective effect of borneol on neurons and the microglia were assessed in vivo and in vitro. We observed that borneol attenuated brain neuronal and microglial inflammation in LPS-induced sepsis mice with a suppression of p-p65 and p38 signaling that were initially activated by LPS in the brain. In vitro examination confirmed that the protective effect of borneol on both neurons and microglia, and its suppressive effect on p-p65 and p38 pathways were, at least in part, direct. An early protection of neurons and microglia from bacterial endotoxin during sepsis is beneficial, and borneol has the potential to protect these cells. [ABSTRACT FROM AUTHOR]