Aberrant expression of thyroidal hormone receptor α exasperating mitochondrial dysfunction induced sarcopenia in aged mice.

Disrupted mitochondrial dynamics and mitophagy contribute to functional deterioration of skeletal muscle (SM) during aging, but the regulatory mechanisms are poorly understood. Our previous study demonstrated that the expression of thyroid hormone receptor α (TRα) decreased significantly in aged mice, suggesting that the alteration of thyroidal elements, especially the decreased TRα, might attenuate local THs action thus to cause the degeneration of SM with aging, while the underlying mechanism remains to be further explored. In this study, decreased expression of myogenic regulators Myf5, MyoD1, mitophagy markers Pink1, LC3II/I, p62, as well as mitochondrial dynamic factors Mfn1 and Opa1, accompanied by increased reactive oxygen species (ROS), showed concomitant changes with reduced TRα expression in aged mice. Further TRα loss- and gain-of-function studies in C2C12 revealed that silencing of TRα not only down-regulated the expression of above-mentioned myogenic regulators, mitophagy markers and mitochondrial dynamic factors, but also led to a significant decrease in mitochondrial activity and maximum respiratory capacity, as well as more mitochondrial ROS and damaged mitochondria. Notedly, overexpression of TRα could up-regulate the expression of those myogenic regulators, mitophagy markers and mitochondrial dynamic factors, meanwhile also led to an increase in mitochondrial activity and number. These results confirmed that TRα could concertedly regulate mitochondrial dynamics, autophagy, and activity, and myogenic regulators rhythmically altered with TRα expression. Summarily, these results suggested that the decline of TRα might cause the degeneration of SM with aging by regulating mitochondrial dynamics, mitophagy and myogenesis.

An evaluation of bone depth at different three-dimensional paths in infrazygomatic crest region for miniscrew insertion: A cone beam computed tomography study.

Objective: To investigate the difference and distribution of bone depth at different three-dimensional simulated paths to help optimize the insertion path for miniscrew placement in the infrazygomatic crest. Methods: Cone beam computed tomography scans of 80 adults (38 males and 42 females; mean age, 27.0 years) were assessed. For each subject, bone depth of 81 simulated insertion paths at different insertion points and three-dimensional angulations was measured in 160 infrazygomatic crests; the differences were evaluated using the adjusted Friedman test. The bone deficiency ratio for each path was calculated. Distributions of measurements were analyzed and reported as specially designed colormaps. Results: Bone depth increased, and bone deficiency ratio reduced mesially to distally (P < 0.001), apically to coronally (P < 0.01), and at a greater gingival and distal inclination (P < 0.05). The maximum bone depth (10.72 mm) was observed 13 mm above the maxillary occlusal plane in the mesiobuccal root of the maxillary second molar. The minimum bone depth (3.4 mm) was observed 17 mm above the maxillary occlusal plane in the distobuccal root of the maxillary first molar. No bone deficiency was detected at the paths of 13 mm above the maxillary occlusal plane at a gingival inclination of 70° and distal inclination of 30° in the mesiobuccal root of the maxillary second molar. The highest bone deficiency ratio is present 17 mm above the maxillary occlusal plane at a gingival inclination of 60° and a distal inclination of 0° in the distobuccal root of the maxillary first molar (89/160). Conclusion: Insertion paths located at 13 mm above the maxillary occlusal plane in the mesiobuccal root of the maxillary second molar were optimal. A gingival inclination of 70° and a distal inclination of 30° could be beneficial. The distobuccal root of the maxillary first molar region or above the 17 mm insertion plane may not be recommended.

Auricularia auricula Anionic Polysaccharide Nanoparticles for Gastrointestinal Delivery of Pinus koraiensis Polyphenol Used in Bone Protection under Weightlessness.

Auricularia auricula polysaccharides used in Pinus koraiensis polyphenol encapsulation and delivery under weightlessness are rarely reported. In this study, an anionic polysaccharide fragment named AAP Iα with a molecular weight of 133.304 kDa was isolated and purified to construct a polyphenol encapsulation system. Nanoparticles named NPs-PP loaded with a rough surface for Pinus koraiensis polyphenol (PP) delivery were fabricated by AAP Iα and ε-poly-L-lysine (ε-PL). SEM and the DLS tracking method were used to observe continuous changes in AAP Iα, ε-PL and PP on the nanoparticles' rough surface assembly, as well as the dispersion and stability. Hydrophilic, monodisperse and highly negative charged nanoparticles can be formed at AAP Iα 0.8 mg/mL, ε-PL 20 µg/mL and PP 80 µg/mL. FT-IR was used to determine their electrostatic interactions. Release kinetic studies showed that nanoparticles had an ideal gastrointestinal delivery effect. NPs-PP loaded were assembled through electrostatic interactions between polyelectrolytes after hydrogen bonding formation in PP-AAP Iα and PP-ε-PL, respectively. Colon adhesion properties and PP delivery in vivo of nanoparticles showed that NPs-PP loaded had high adhesion efficiency to the colonic mucosa under simulated microgravity and could enhance PP bioavailability. These results suggest that AAP Iα can be used in PP encapsulation and delivery under microgravity in astronaut food additives.

Neoadjuvant chemoimmunotherapy shows major pathological response and low recurrence in head and neck squamous cell carcinoma.

BACKGROUND: The study aimed to investigate the efficacy and survival outcomes of neoadjuvant chemotherapy combined with programmed cell death protein 1 (PD-1) blockade (neoadjuvant chemoimmunotherapy) for patients with resectable head and neck squamous cell carcinoma (HNSCC). METHODS: A retrospective analysis was conducted. Patients with initially diagnosed, resectable HNSCCs who received the neoadjuvant chemoimmunotherapy and radical surgery were included. Correlation analysis between patients' clinical characteristics and pathological responses, and survival analysis were performed. RESULTS: A total of 79 patients were included. The majority of patients (55, 69.6%) were diagnosed at locally advanced stages and most of them (58, 73.4%) had tumor located at the oral cavity. Nearly half of patients (35, 44.3%) received two cycles of neoadjuvant chemoimmunotherapy and the rest had three or more cycles. The R0 resection rate was 98.7%. In the pathological evaluation, 53.1% of patients reached pathological complete responses or major pathological responses. After a median follow-up of 17.0 months, the 1-year disease-free survival (DFS) and overall survival (OS) rates were 87.2% and 97.4%, respectively. The pathological response showed a significantly positive association with survival benefits (p < 0.001). Patients with human papillomavirus (HPV)-positive oropharyngeal cancer had the best pathological response and survival outcomes. Besides, history of radiation at head and neck region and poor pathological response were found to be independent risk factors of DFS for patients receiving such treatments. CONCLUSION: Neoadjuvant chemoimmunotherapy of HNSCC showed high rate of pathological response and low recurrence rate, holding promise for becoming the new standard of care for resectable HNSCC.

TT3, a More Practical Indicator for Evaluating the Relationship Between Sarcopenia and Thyroid Hormone in the Euthyroid Elderly Compared with FT3.

Background and Aims: Sarcopenia is a common disease in the elderly, and the thyroid hormone (TH) might participate in the pathogenesis of sarcopenia. However, the results of previous studies were not completely consistent. We performed this study to investigate the association between THs and sarcopenia in a Chinese elderly euthyroid population. Subjects and Methods: A total of 309 Chinese elderly euthyroid subjects with an average age of 85.19 ± 7.8 years were enrolled. Participants were divided into four groups (non-sarcopenia, possible sarcopenia, sarcopenia and serve sarcopenia) according to the consensus update of AWGS in 2019. Serum levels of TT3, FT3, TT4, FT4, TSH, rT3 and TBG were measured. Muscle mass was measured by multifrequency bioelectrical impedance analysis, hand grip (HG) was represented by spring-type dynamometer, and gait speed (GS) was determined by 6-metre walk test. The FRAIL scale was used to assess frailty. Results: Compared to the non-sarcopenia group, the sarcopenia group showed a significant increase in age and FRIAL score, while FT3 and TT3 levels decreased significantly. Partial correlation analysis (adjusted by age, gender and the scores of FRIAL scale) indicated that FT3, TT3 and TSH had significant positive correlations with HG, and there also was a significant positive correlation between TT3 and GS. In addition, after adjusting for age, gender, BMI, ALT, sCr, and score on the FRAIL scale, the multivariate linear regression analysis showed that TT3 was positively associated with muscle strength and negatively associated with sarcopenia risk. Conclusion: There is an association between the low TT3 level and sarcopenia. Therefore, maintaining higher T3 concentrations within the normal range appears to be beneficial for sarcopenia in the elderly. In addition, due to the fluctuation of FT3, TT3 is a more stable and practical indicator to evaluate the relationship between sarcopenia and thyroid hormone in the elderly euthyroid population.

Docetaxel-induced cognitive impairment in rats can be ameliorated by edaravone dexborneol: Evidence from the indicators of biological behavior and anisotropic fraction.

Objective: This study aimed to investigate the effect of Edaravone Dexborneol (ED) on impaired learning and memory in docetaxel (DTX)-treated rats using cognitive behavior assessments and magnetic resonance diffusion tensor imaging (DTI). Materials and methods: In total, 24 male Sprague-Dawley rats were divided into control, low-dose DTX (L-DTX) model, and high-dose DTX(H-DTX) model groups, with eight rats in each group, numbered 1-8. The rats were intraperitoneally injected with 1.5 mL of either normal saline (control group), or 3 mg/kg and 6 mg/kg DTX (L-DTX and H-DTX groups, respectively), once a week for 4 weeks. The learning and memory abilities of each group were tested using a water maze. At the end of the water maze test, rats 1-4 in each group were treated with ED (3 mg/kg, 1 mL), and rats 5-8 were injected with an equal volume of normal saline once a day for 2 weeks. The learning and memory abilities of each group were evaluated again using the water maze test, and the image differences in the hippocampus of each group were analyzed using DTI. Results: (1) H-DTX group (32.33 ± 7.83) had the longest escape latency, followed by the L-DTX group (27.49 ± 7.32), and the Control group (24.52 ± 8.11) having the shortest, with the difference being statistically significant (p < 0.05). (2) Following ED treatment, compared to rats treated with normal saline, the escape latency of the L-DTX (12.00 ± 2.79 vs. 10.77 ± 3.97, p < 0.05), and the H-DTX (12.52 ± 3.69 vs. 9.11 ± 2.88, p < 0.05) rats were significantly shortened. The residence time in the target quadrant of H-DTX rats was significantly prolonged (40.49 ± 5.82 vs. 55.25 ± 6.78, p < 0.05). The CNS damage in the L-DTX rats was repaired to a certain extent during the interval between the two water maze tests (28.89 ± 7.92 vs. 12.00 ± 2.79, p < 0.05). (3) The fractional anisotropy (FA) value of DTI in the hippocampus of rats in the different groups showed variable trends. After treatment with ED, though the FA values of most areas in the hippocampus of rats in L-DTX and H-DTX groups were higher than before, they did not reach the normal level. Conclusion: ED can ameliorate the cognitive dysfunctions caused by DTX in rats by improving the learning and memory impairment, which is reflected in the recovery of biological behavior and DTI indicators of the hippocampus.

Efficacy of the enhanced recovery after surgery protocol in operating room nursing of patients following single-port video-assisted thoracoscopic lung cancer surgery: A retrospective study.

This study assessed the efficacy of the enhanced recovery after surgery (ERAS) protocol in operating room nursing care for patients who underwent single-port video-assisted thoracoscopic lung cancer surgery. The study included 82 surgical lung cancer cases. The patients underwent single-port video-assisted thoracoscopic lung cancer surgery between April 1, 2021, and June 31, 2022. Of the 82 patients, 42 received nursing care under the ERAS protocol (experimental group) and 40 had routine nursing care (control group) in the operation room. Based on the 2 different nursing care approaches, the postoperative functional recovery efficacy, quality of life, postoperative complications, and psychological status were compared between the 2 groups. In our analysis, the mean anal venting time, average early out-of-bed time, the average time to liquid resumption, atelectasis, and pulmonary infection rate were significantly lower in the experimental group than in the control group (P < .05). The Self-Rating Depression Scale (SDS) and the Self-Rating Anxiety Scale (SAS) scores were also significantly lower in the experimental group than in the control group (P < .05). Other indicators were not significantly different between the 2 groups. Our results show that the implementation of an ERAS protocol in operating room nursing care is feasible and should be clinically applied. The ERAS protocol may enhance the recovery of patients who underwent single-port video-assisted thoracoscopic lung cancer surgery.

CMTM6 recruits T cells within the endocervical adenocarcinoma microenvironment and suppresses cell proliferation via the p53 pathway.

Endocervical adenocarcinoma (ECA), harboring poor prognosis, is divided into human papilloma virus (HPV)-associated adenocarcinoma (HPVA) and non-HPVA (NHPVA), each consisting of a heterogeneous immune microenvironment. We aim to examine the effect of CKLF-like MARVEL transmembrane domain 6 (CMTM6), a key regulator of PD-L1, on ECA. Immunohistochemistry and RNA-sequencing (RNA-seq) were used to detect CMTM6, Programmed death ligand 1 (PD-L1), and immune cells biomarkers levels in tumors. RT-qPCR and Western Blotting were used to detect the mRNA and protein level changed in cells. The expression of CMTM6 in ECA is upregulated compared to cervical squamous cell carcinoma tissues. More infiltrating T cells were observed in CMTM6high ECA tissues, especially in CMTM6high HPVA. Higher expression of CMTM6 is associated with a higher rate of infiltrating CD8+ T cells in HPVA, but not in NHPVA. ECA patients were divided into three groups according to the co-expression status of CMTM6 and PD-L1(CPS) . Patients with CMTM6high /PD-L1(CPS+) had the longest OS and DFS, especially in NHPVA patients. Moreover, knock down of CMTM6 promotes ECA cell proliferation via the p53 pathway. CMTM6 recruits T cells, suppresses ECA cell proliferation via the p53 pathway and can be used as a novel prognostic indicator for ECA patients.

Objective sleep characteristics and continuous glucose monitoring profiles of type 2 diabetes patients in real-life settings.

AIM: To investigate the association between objective sleep parameters and glycaemic variability determined by continous glucose monitoring (CGM) among patients with type 2 diabetes, given the significant role of sleep in glycaemic control. METHODS: In this study, CGM was carried out in 28 patients with T2D (aged 62.3 ± 4.8 years, 57% women). Sleep characteristics were assessed by actigraphy within the CGM period. CGM-derived outcomes included glucose level, and percentages of time in range (TIR) and time above range (TAR) during the monitoring period. Associations between intraindividual night-to-night variations in sleep characteristics and overall CGM outcomes were analysed using linear regression. Associations between sleep characteristics during each night and time-matched CGM outcomes were analysed using linear mixed models. RESULTS: A total of 249 person-days of CGM, coupled with 221 nights of sleep characteristics, were documented. Greater standard deviation (SD) of objective sleep duration (minutes) between measurement nights was associated with higher glucose level (coefficient 0.018 mmol/L [95% confidence interval {CI} 0.004, 0.033], P = 0.017), smaller proportion of TIR (% in observation period; coefficient -0.20% [95% CI -0.36, -0.03], P = 0.023), and greater proportion of TAR (coefficient 0.22% [95% CI 0.06, 0.39], P = 0.011). Later sleep midpoint (minutes from midnight) was associated with greater SD of glucose during the same sleep period (coefficient 0.002 minutes [95% CI 0.0001, 0.003], P = 0.037), longer nocturnal sleep duration was associated with smaller coefficient of variation of glucose level in the upcoming day (-0.015% [95% CI -0.03, -0.001], P = 0.041). CONCLUSION: Objectively determined sleep duration and sleep midpoint, as well as their daily variability, are associated with CGM-derived glucose profiles in T2D patients.

Risk factors for musculoskeletal disorders among takeaway riders: Up-to-date evidence in Shanghai, China.

Background: Musculoskeletal disorders (MSDs) are common occupational diseases. However, the influencing mechanisms were not clear in the new emerging takeaway rider occupation in the catering industry in China. Methods: A cross-sectional study was conducted using a takeaway rider sample from one of the largest e-platforms, the Mei Tuan Company in Shanghai. The chi-square test was used to compare the sex differences in MSDs according to various factors. Binary logistic regressions were then performed to explore the potential risk factors for the occurrence and severity of MSDs adjusted by age, sex and vehicle type. Crude odds ratios (CORs) and adjusted odds ratios (AORs) and their 95% confidence intervals (CIs) for predictors were reported. Results: The prevalence of MSDs was found to be 54.9% (n = 361). Shoulders (joint pain: 24.5%, n = 154/629 cases; muscle pain: 29.0%, n = 183/632 cases; muscle numbness: 31.7%, n = 120/379 cases) and neck (joint pain: 17.0%, n = 107/629 cases; muscle pain: 14.1%, n = 89/632 cases; muscle numbness: 15.3%, n = 58/379 cases) were the most affected regions. Irregular meals (often having regular meals: p = 0.03, AOR = 1.89, 95% CI: 1.05-3.39; sometimes: p < 0.01, AOR = 2.54, 95% CI: 1.49-4.34 and seldomly: p < 0.01, AOR = 4.24, 95% CI: 2.28-7.91) were positively associated with the occurrence of MSDs. Work-related factors, including working over 5 years (p = 0.02, AOR = 1.87, 95% CI: 1.10-3.17) and over 51 km of food delivery distance per day (51-75 km: p = 0.02, AOR = 2.13, 95CI%:1.13-4.01; ≥76 km: p < 0.01, AOR = 3.12, 95CI%: 1.44-6.77), were strongly associated with severity. Conclusion: MSDs were common among takeaway riders. Personal lifestyles (meal irregularity) were found to predict the occurrence, while work-related factors (longer years of employment and prolonged food delivery distance) were positively associated with severity. Public health efforts should be made to prevent MSDs in this population.

Study on Dynamic Probability and Quantitative Risk Calculation Method of Domino Accident in Pool Fire in Chemical Storage Tank Area.

The domino event caused by fire is one of the common accidents in hydrocarbon storage tank farms, which further expands the severity and scope of the accident. Due to the different failure sequence of the storage tanks in a domino accident, the radiant heat generated by the failed storage tank to the target tank is different. Based on the influence of this synergistic effect, this study combined the Monte Carlo algorithm and FSEM, and proposed a fast real-time probability calculation method for a fire domino accident in a storage tank area, for the first time. This method uses the Monte Carlo algorithm to simulate all accident scenarios, and obtains the evolution of multiple escalation fire domino accidents under the synergistic effect according to FSEM, and then calculates the real-time failure probability and risk. Based on a comprehensive analysis of the accident propagation path, this method avoids the problem of a large amount of calculation, and is conducive to the rapid and effective analysis of the fire risk in a storage tank area and the formulation of corresponding risk reduction measures. The effectiveness and superiority of the proposed method were proved by a case study.

An inulin-type fructan (AMP1-1) from Atractylodes macrocephala with anti-weightlessness bone loss activity.

Atractylodes macrocephalon polysaccharides of alleviating weightlessness-induced bone loss (WIBL) are rarely reported. In this study, a neutral polysaccharide fragment named AMP1-1 was isolated and purified. Monosaccharide composition and gel permeation chromatography analysis indicated that AMP1-1 was composed of glucose and fructose with molecular weight of 1.433 kDa. Based on data of gas chromatography-mass spectrometer (GCMS), a linear backbone consisted of α-d-Glcp-(1→ and →1)-ß-d-Fruf-2→ was discovered. Combining results from nuclear magnetic resonance (NMR), the inulin-type fructan AMP1-1 was identified as α-d-Glcp-1→(2-ß-d-Fruf-1)7. Anti-WIBL activity of AMP1-1 was evaluated though analyzation of mechanical properties, BALP and TRAP 5b activities on femur. In vitro mRNA expression indicated that anti-WIBL activity of AMP1-1 was achieved by promote bone formation and inhibit bone resorption in primary osteoblasts and RAW264.7 cell lines under simulated weightlessness. In conclusion, the inulin-type fructan AMP1-1 with α-d-Glcp-1→(2-ß-d-Fruf-1)7 had anti-WIBL activity via remodeling bone homeostasis.

The Effect of Modified Tai Chi Exercises on the Physical Function and Quality of Life in Elderly Women With Knee Osteoarthritis.

Background: Knee osteoarthritis (KOA) is the leading cause of pain and stiffness, affecting older adults' physical function and quality of life. As a form of mind-body exercise, Tai Chi has been recommended as an exercise prescription for KOA patients. This study examined the effects and continuation of modified Tai Chi exercises on physical function and quality of life in elderly women with KOA. Methods: We conducted a single-blind, randomized controlled trial (RCT) on 40 older women with KOA. The participants were randomized to a 12 weeks Tai Chi or control group. The Tai Chi group attended a kind of modified Tai Chi training sessions three times per week; the control group attended wellness education sessions once a week. The primary outcome was the Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Secondary outcomes were the Berg Balance Scale (BBS), Timed Up and Go (TUG), Short-Form 36 (SF-36), Pittsburgh Sleep Quality of Index (PSQI), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). Results: After the 12-weeks the Tai Chi group showed significan improvement in the WOMAC pain (mean difference, -5.09 points, p = 0.001), WOMAC stiffness (mean difference, -3.60 points, p = 0.002), WOMAC physical function (mean difference, -11.21 points, p = 0.001) compared to the control group. In addition, the Tai Chi group had also significant improvement in the BBS (mean difference, 1.70 points, p = 0.008), TUG (mean difference, -0.52s, p = 0.001), SF-36PCS (mean difference, 7.60 points, p = 0.001), MCS (mean difference, 7.30 points, p = 0.001), PSQI (mean difference, -3.71 points, p = 0.001), SDS (mean difference, -5.37 points, p = 0.025) and SAS (mean difference, -5.06 points, p = 0.002). Conclusion: The modified Tai Chi exercises are an effective treatment for improved physical function and quality of life in elderly women with KOA. Clinical Trial Registration: The trial was registered in Chinese Clinical Trial Registry (ChiCTR2000040721), http://www.chictr.org.cn/edit.aspx?pid=65419&htm=4.

[Exploration of multi-faceted model in plant biology teaching].

Plant biology is a basic course for students majoring in biological science. Under the guidance of developmental biology, we have constructed a comprehensive, systematic and dynamic new curriculum system for plant biology. There are still some problems existing in the current curriculum teaching mode, e.g. the students do not listen carefully to the lecture due to single classroom teaching mode, the mismatch between theoretical and experimental courses in terms of content and timing, the incomplete understanding on plants and the difficulty of integrating learning and practicing due to insufficient field practices. In view of these problems, a series of new teaching strategies for bioscience major of Harbin Institute of Technology were proposed and implemented. The combination of lectures and high quality massive open online courses (MOOC) were used for theoretical study, to which the flipped classroom was added. In addition, the theoretical study and the experiment work were combined. Moreover, the plant cognitive practices were carried out in the campus and the botanical garden in early spring, late spring and summer, respectively. Satisfactory results were achieved after two rounds of teaching practice, which fulfilled the education requirements and laid foundations for students to continue follow-up basic and professional courses.

Monitoring and Predictive Maintenance of Centrifugal Pumps Based on Smart Sensors.

Centrifugal pumps have a wide range of applications in industrial and municipal water affairs. During the use of centrifugal pumps, failures such as bearing wear, blade damage, impeller imbalance, shaft misalignment, cavitation, water hammer, etc., often occur. It is of great importance to use smart sensors and digital Internet of Things (IoT) systems to monitor the real-time operating status of pumps and predict potential failures for achieving predictive maintenance of pumps and improving the intelligence level of machine health management. Firstly, the common fault forms of centrifugal pumps and the characteristics of vibration signals when a fault occurs are introduced. Secondly, the centrifugal pump monitoring IoT system is designed. The system is mainly composed of wireless sensors, wired sensors, data collectors, and cloud servers. Then, the microelectromechanical system (MEMS) chip is used to design a wireless vibration temperature integrated sensor, a wired vibration temperature integrated sensor, and a data collector to monitor the running state of the pump. The designed wireless sensor communicates with the server through Narrow Band Internet of Things (NB-IoT). The output of the wired sensor is connected to the data collector, and the designed collector can communicate with the server through 4G communication. Through cloud-side collaboration, real-time monitoring of the running status of centrifugal pumps and intelligent diagnosis of centrifugal pump faults are realized. Finally, on-site testing and application verification of the system was conducted. The test results show that the designed sensors and sensor application system can make good use of the centrifugal pump failure mechanism to automatically diagnose equipment failures. Moreover, the diagnostic accuracy rate is above 85% by using the method of wired sensor and collector. As a low-cost and easy-to-implement solution, wireless sensors can also monitor gradual failures well. The research on the sensors and pump monitoring system provides feasible methods and an effective means for the application of centrifugal pump health management and predictive maintenance.

Simulated Microgravity Increases the Permeability of HUVEC Monolayer through Up-Regulation of Rap1GAP and Decreased Rap2 Activation.

Space microgravity condition has great physiological influence on astronauts' health. The interaction of endothelial cells, which control vascular permeability and immune responses, is sensitive to mechanical stress. However, whether microgravity has significant effects on the physiological function of the endothelium has not been investigated. In order to address such a question, a clinostat-based culture model with a HUVEC monolayer being inside the culture vessel under the simulated microgravity (SMG) was established. The transmittance of FITC-tagged dextran was used to estimate the change of integrity of the adherens junction of the HUVEC monolayer. Firstly, we found that the permeability of the HUVEC monolayer was largely increased after SMG treatment. To elucidate the mechanism of the increased permeability of the HUVEC monolayer under SMG, the levels of total expression and activated protein levels of Rap1 and Rap2 in HUVEC cells, which regulate the adherens junction of endothelial cells, were detected by WB and GST pull-down after SMG. As the activation of both Rap1 and Rap2 was significantly decreased under SMG, the expression of Rap1GEF1 (C3G) and Rap1GAP in HUVECs, which regulate the activation of them, was further determined. The results indicate that both C3G and Rap1GAP showed a time-dependent increase with the expression of Rap1GAP being dominant at 48 h after SMG. The down-regulation of the expression of junctional proteins, VE-cadherin and ß-catenin, in HUVEC cells was also confirmed by WB and immunofluorescence after SMG. To clarify whether up-regulation of Rap1GAP is necessary for the increased permeability of the HUVEC monolayer after SMG, the expression of Rap1GAP was knocked down by Rap1GAP-shRNA, and the change of permeability of the HUVEC monolayer was detected. The results indicate that knock-down of Rap1GAP reduced SMG-induced leaking of the HUVEC monolayer in a time-dependent manner. In total, our results indicate that the Rap1GAP-Rap signal axis was necessary for the increased permeability of the HUVEC monolayer along with the down-regulation of junctional molecules including VE-cadherin and ß-catenin.

Ultrahigh-level enhancement on nonlinear optical susceptibility of cubic quantum dots achieved by THz laser and electric field.

Multi-physics coupling, composed of an intense THz laser and electric field, serves as a new approach to realize the ultrahigh-level enhancement on third-harmonic generation (THG) of cubic quantum dots (CQDs). The exchange of quantum states caused by anticrossing of intersubbands is demonstrated by the Floquet method and finite difference method with the increasing laser-dressed parameter and electric field. The results show that the rearrangement of the quantum states excites the THG coefficient of CQDs four orders of magnitude higher than that achieved with a single physical field. The optimal polarization direction of incident light that maximizes the THG exhibits strong stability along the z axis at high laser-dressed parameter and electric field.

CT-Based Peritumoral and Intratumoral Radiomics as Pretreatment Predictors of Atypical Responses to Immune Checkpoint Inhibitor Across Tumor Types: A Preliminary Multicenter Study.

OBJECTIVE: To develop and validate a new strategy based on radiomics features extracted from intra- and peritumoral regions on CT images for the prediction of atypical responses to the immune checkpoint inhibitor (ICI) in cancer patients. METHODS: In total, 135 patients derived from five hospitals with pathologically confirmed malignancies receiving ICI were included in this retrospective study. Atypical responses including pseudoprogression (PsP) and hyperprogression disease (HPD) were identified as their definitions. A subgroup of standard progression disease (sPD) in 2018 was also involved in this study. Based on pretreatment CT imaging, a total of 107 features were extracted from intra- and peri-tumoral regions, respectively. The least absolute shrinkage and selection operator (Lasso) algorithm was used for feature selection, and multivariate logistic analysis was used to develop radiomics signature (RS). Finally, a total of nine RSs, derived from intra-tumoral, peri-tumoral, and combination of both regions, were built respectively to distinguish PsP vs. HPD, PsP vs. sPD, and HPD vs. sPD. The performance of the RSs was evaluated with discrimination, calibration, and clinical usefulness. RESULTS: No significant difference was found when compared in terms of clinical characteristics of PsP, HPD, and sPD. RS based on combined regions outperformed those from either intra-tumoral or peri-tumoral alone, yielding an AUC (accuracy) of 0.834 (0.827) for PsP vs. HPD, 0.923 (0.868) for PsP vs. sPD, and 0.959 (0.894) for HPD vs. sPD in the training datasets, and 0.835 (0.794) for PsP vs. HPD, 0.919 (0.867) for PsP vs. sPD, and 0.933 (0.842) for HPD vs. sPD in the testing datasets. The combined RS showed good fitness (Hosmer-Lemeshow test p > 0.05) and provided more net benefit than the treat-none or treat-all scheme by decision curve analysis in both training and testing datasets. CONCLUSION: Pretreatment radiomics are helpful to predict atypical responses to ICI across tumor types. The combined RS outperformed those from either intra- or peri-tumoral alone which may provide a more comprehensive characterization of atypical responses to ICI.

Protective Effects of Sal B on Oxidative Stress-Induced Aging by Regulating the Keap1/Nrf2 Signaling Pathway in Zebrafish.

The models of oxidative damage-induced aging were established by adding ethanol (C2H5OH), hydrogen peroxide (H2O2) and 6-hydroxydopamine (6-OHDA) to zebrafish embryos in this research. To find effective protective drugs/foods, Salvianolic acid B (Sal B) was added after the embryos were treated by these oxidative reagents. After being treated with ethanol, H2O2 and 6-OHDA, the morphological changes were obvious and the deformities included spinal curvature, heart bleeding, liver bleeding, yolk sac deformity and pericardial edema, and the expression of oxidative stress-related genes Nrf2b, sod1 and sod2 and aging-related genes myl2a and selenbp1 were significantly up-regulated compared to the control group. While after adding 0.05 µg/mL and 0.5 µg/mL Sal B to the ethanol-treated group, death rates and MDA levels decreased, the activity of antioxidant enzyme (SOD, CAT and GSH-Px) changed and Nrf2b, sod1, sod2, myl2a, selenbp1, p53 and p21 were down-regulated compared to the ethanol-treated group. The bioinformatics analysis also showed that oxidative stress-related factors were associated with a variety of cellular functions and physiological pathways. In conclusion, Sal B can protect against aging through regulating the Keap1/Nrf2 pathway as well as antioxidative genes and enzyme activity.