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In rehabilitation, physicians plan lower-limb exercises via linear guidance. Ensuring efficacy and safety, they design patient-specific paths, carefully plotting smooth trajectories to minimize jerks. Replicating their precision in robotics is a major challenge. This study introduces a linear rehabilitation motion planning method designed for physicians to use a multi-posture lower-limb rehabilitation robot, encompassing both path and trajectory planning. By subdividing the lower limb's action space into four distinct training sections and classifying this space, we articulate the correlation between linear trajectories and key joint rehabilitation metrics. Building upon this foundation, a rehabilitative path generation system is developed, anchored in joint rehabilitation indicators. Subsequently, high-order polynomial curves are employed to mimic the smooth continuity of traditional rehabilitation trajectories and joint motions. Furthermore, trajectory planning is refined through the resolution of a constrained quadratic optimization problem, aiming to minimize the abrupt jerks in the trajectory. The optimized trajectories derived from our experiments are compared with randomly generated trajectories, demonstrating the suitability of trajectory optimization for real-time rehabilitation trajectory planning. Additionally, we compare trajectories generated based on the two groups of joint rehabilitation indicators, indicating that the proposed path generation system effectively assists clinicians in executing efficient and precise robot-assisted rehabilitation path planning.

Clustered regularly interspaced short palindromic repeats (CRISPR) molecular diagnostic technology is one of the most reliable diagnostic tools for infectious diseases due to its short reaction time, high sensitivity, and excellent specificity. However, compared with fluorescent polymerase chain reaction (PCR) technology, CRISPR molecular diagnostic technology lacks high-throughput automated instrumentation and standardized detection reagents for high sensitivity, limiting its large-scale clinical application. In this study, a high-throughput automated device was developed by combining reagent lyophilization, extraction-free technology, and a one-pot consumable system. This innovative approach enabled the rapid sample-in-result-out detection of 48 samples in 25 min and demonstrated high sensitivity and specificity for the qualitative analysis of clinical samples. The obtained results show that the detection limit of the designed system for African swine fever virus (ASFV) is 0.5 copies/μL. As a proof concept, a single-tube dual-target nucleic acid detection method was developed, achieving a detection limit of 5 copies/μL for the ORF1ab and N genes of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) within 45 min. The method is highly specific, reliable, and stable, providing a feasible solution for the clinical application of CRISPR nucleic acid detection technology.

Aims: Insulin resistance (IR) is an important risk factor for obesity and cardiometabolic diseases, and our previous findings have demonstrated that visceral fat area to skeletal muscle mass ratio (VSR) is significantly and positively associated with the risk of cardiometabolic diseases. Hence, this study aimed to investigate the relationship between VSR and multiorgan IR, provide a new approach to improve body composition, and set the basis for VSR to increase the incidence of cardiometabolic diseases. Materials and Methods: The study included 398 patients who underwent anthropometric and biochemical measurements, and body composition assessment. Spearman correlation analysis was used to investigate the correlation between VSR and homeostatic model assessment for insulin resistance (HOMA-IR) as well as multiorgan IR, including homeostasis model assessment adiponectin (HOMA-AD), adipose tissue insulin resistance (ADIPO-IR), and hepatic insulin sensitivity (HISI). The new model that incorporated into the present study is made up of easily measured biochemical indicators and is used to predict IR. Logistic regression was used to analyze the odds ratio (OR) of VSR on the risk of multiorgan IR. The predictive value of VSR for HOMA-IR and new model was evaluated using the receiver operating characteristic (ROC) curve. Results: VSR was significantly associated with HOMA-IR, HOMA-AD, ADIPO-IR, 1/HISI, and new model ( p < 0.001). With the increase of VSR, the OR increased significantly for HOMA-IR and new model ( p < 0.001). Then, multiorgan IR indicators were quantified, compared to the lowest quartile group, and increased VSR exacerbated the risk of IR in the highest quartile ( p trend < 0.001). The area under the curve for predicting IR using VSR for HOMA-IR and new model was 0.88 for men, 0.85 for women and 0.73 for men, 0.76 for women, respectively. Conclusions: There was significant correlation between VSR and multiorgan IR, and the risk of multiorgan IR increased with increasing VSR. Trial Registration: Clinical Trial Registry identifier: ChiCTR2100044305., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Yanju Zhang et al.)

Background: Insulin resistance (IR) is a key feature of type 2 diabetes (T2D) and an independent risk factor for metabolic syndrome. Previous studies have linked elevated serum uric acid (SUA) to an increased risk of T2D., Aim: The purpose of this study was to investigate the relationship between SUA and IR. At the same time, the correlation between New model and SUA compared with other IR alternatives was compared, so as to provide a simple and effective new indicator for early detection and prediction of IR risk and early prevention of T2D., Methods: The first cohort was the Discovery Cohort, which included 318 obese patients. And the second cohort was the Verification Cohort, which included a total of 4333 subjects who underwent a routine health checkup at our hospital. Spearman correlation analysis and binary logistic regression analysis were used to discuss the correlation between SUA and IR., Results: Regardless of sex, fasting insulin (FINS) and IR replacement markers increased with SUA (P<0.001). In both cohorts, SUA was associated with IR alternatives, especially with New model, and differed between men and women in all correlation analyses. After adjusting for confounding factors, SUA was still associated with IR (P<0.001)., Conclusion: The correlation between SUA and IR was significantly stronger in women than in men. And the correlation between SUA and New model is stronger than other IR replacement models. However, the causal relationship between SUA and IR has not been clearly established., Competing Interests: The authors participating in this study declare that they have no conflicts of interest., (© 2024 Liu et al.)

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by increased sensitivity to environmental allergens and irritants. Icariin, a natural compound extracted from the herb Epimedium, has been traditionally used for its potential anti-inflammatory and antioxidant properties. This study aimed to investigate the regulatory effects of icariin on AD-like symptoms and to elucidate its underlying mechanisms. The effects of icariin on TNF-α/IFN-γ-induced HaCaT cell injury were assessed using various assays, including cell counting kit-8 for cell viability, flow cytometry for reactive oxygen species (ROS) levels, and colorimetric assays for malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. In addition, the study performed enzyme-linked immunosorbent assays to assess cytokines (IL-1β, IL-6, and IL-8) and chemokines (MDC, TARC, and RANTES) levels. Flow cytometry was used to quantify apoptotic rate, while a wound-healing assay was conducted to assess cell migration. The expression of WT1 associated protein (WTAP) and serpin family B member 4 (SERPINB4) at the mRNA and protein levels was determined using qRT-PCR and western blotting, respectively. The associations between WTAP and SERPINB4 were analyzed using RNA immunoprecipitation assay and m6A RNA immunoprecipitation assay. Icariin treatment significantly mitigated TNF-α/IFN-γ-induced oxidative stress, inflammatory response, and apoptosis in HaCaT cells, while also reversing the inhibitory effect on cell migration. Icariin reduced the expression of WTAP in TNF-α/IFN-γ-stimulated HaCaT cells. Overexpression of WTAP reversed the effects of icariin in TNF-α/IFN-γ-stimulated HaCaT cells. WTAP silencing inhibited the mRNA stability of SERPINB4 through the m6A modification. SERPINB4 overexpression attenuated the effects of WTAP silencing on oxidative stress, inflammatory response, apoptosis, and migration of TNF-α/IFN-γ-stimulated HaCaT cells. Icariin treatment downregulated SERPINB4 expression by regulating WTAP in TNF-α/IFN-γ-stimulated HaCaT cells. Icariin ameliorated TNF-α/IFN-γ-induced human immortalized epidermal cell injury through the WTAP/SERPINB4 axis, highlighting the potential for targeted interventions in AD pathogenesis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Interleukin-27 (IL-27), a potential mediator linking obesity to inflammatory diseases, is considered an important candidate for regulating obesity. The present study evaluated the relationship of IL-27 with obesity and insulin resistance (IR) and further investigated the changes in IL-27 levels after weight loss., Methods: The study analyzed 405 participants, of whom 62 with overweight or obesity completed one year of lifestyle intervention. The body compositions, including percent of body fat (PBF), visceral fat area (VFA), skeletal muscle mass (SMM), and visceral fat area to skeletal muscle mass ratio (VSR), were assessed using the bioelectrical impedance analysis method. Serum IL-27 levels were measured using the enzyme-linked immunosorbent assay (ELISA)., Results: IL-27 levels increased significantly with the increase in body mass index (BMI) (P < 0.001). Moreover, IL-27 levels were positively correlated with PBF, VFA, and VSR. Homeostatic model assessment for insulin resistance (HOMA-IR), the inverse of hepatic insulin sensitivity (1/HISI), adipose tissue insulin resistance (Adipo-IR), and homeostasis model assessment-adiponectin (HOMA-AD) increased significantly with each quartile of IL-27 levels (all P < 0.001). IL-27 levels significantly decreased after weight loss (P < 0.001)., Conclusions: IL-27 was positively correlated with obesity, HOMA-IR, 1/HISI, Adipo-IR, and HOMA-AD. IL-27 levels significantly decreased after weight loss., Competing Interests: Declaration of Competing Interest All authors declare that they have no known competing financial interests or personal relationships., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Most lower limb rehabilitation robots are limited to specific training postures to adapt to stroke patients in multiple stages of recovery. In addition, there is a lack of attention to the switching functions of the training side, including left, right, and bilateral, which enables patients with hemiplegia to rehabilitate with a single device. This article presents an exoskeleton robot named the multistage hemiplegic lower-limb rehabilitation robot, which has been designed to do rehabilitation in multiple training postures and training sides. The mechanism consisting of the thigh, calf, and foot is introduced. Additionally, the design of the multi-mode limit of the hip, knee, and ankle joints supports delivering therapy in any posture and training sides to aid patients with hemiplegia in all stages of recovery. The gait trajectory is planned by extracting the gait motion trajectory model collected by the motion capture device. In addition, a control system for the training module based on adaptive iterative learning has been simulated, and its high-precision tracking performance has been verified. The gait trajectory experiment is carried out, and the results verify that the trajectory tracking performance of the robot has good performance.

Cortical folding is a critical process during brain development, resulting in morphologies that are both consistent and distinct between individuals and species. While earlier studies have highlighted important aspects of cortical folding, most existing computational models, based on the differential growth theory, fall short of explaining why folds tend to appear in particular locations. The axon tension hypothesis may provide insight into this conundrum; however, there has been significant controversy about a potential role of axonal tension during the gyrification. The common opinion in the field is that axonal tension is inadequate to drive gyrification, but we currently run the risk of discarding this hypothesis without comprehensively studying the role of axonal tension. Here we propose a novel bi-layered finite element model incorporating the two theories, including characteristic axonal tension in the subcortex and differential cortical growth. We show that axon tension can serve as a perturbation sufficient to trigger buckling in simulations; similarly to other types of perturbations, the natural stability behavior of the system tends to determine some characteristics of the folding morphology ( e.g. the wavelength) while the perturbation determines the location of folds. Certain geometries, however, can interact or compete with the natural stability of the system to change the wavelength. When multiple perturbations are present, they similarly compete with each other. We found that an axon bundle of reasonable size will overpower up to a 5% thickness perturbation (typical in the literature) and determine fold placement. Finally, when multiple axon tracts are present, even a slight difference in axon stiffness, representing the heterogeneity of axonal connections, is enough to significantly change the folding pattern. While the simulations presented here are a very simple representation of white matter connectivity, our findings point to urgent future research on the role of axon connectivity in cortical folding.

Background: Growing evidence has demonstrated the important roles of gut microbiota and short chain fatty acids, especially acetate, propionate and butyrate, in the development of obesity and metabolic diseases. To date, the effects of acetate, propionate and butyrate on human adiposity and glucose metabolism remain controversial. This study aimed to explore the associations of systemically acetate, propionate and butyrate with obesity and glucose homeostasis in patients with type 2 diabetes (T2D) and obesity., Methods: A total of 12 patients with T2D and obesity and 8 age- and sex-matched healthy individuals with BMI <24 kg/m 2 were enrolled in this study. Height, weight, body composition, blood pressure, biochemical indices, a 75-g oral glucose tolerance test, and plasma acetate, propionate and butyrate were measured at baseline. Then, participants in T2D group were given a weight control therapy, in addition to conventional medication, and all the measurements were repeated 12 months from baseline. The direct segmental multi-frequency bioelectrical impedance analysis was used to assess body composition. Acetate, propionate and butyrate levels were determined by liquid chromatography coupled to tandem mass spectrometry., Results: Butyrate concentration significantly increased from baseline after obvious weight loss ( P <0.05). Correlation analysis showed that propionate was negatively correlated with percent of body fat (PBF) and 2-h plasma glucose (2-h PG) ( P <0.05), and butyrate was negatively associated with body mass index, visceral fat area, PBF and 2-h PG ( P <0.05). No association was found between acetate and obesity., Conclusion: Butyrate and propionate are negatively correlated with obesity and glucose levels in patients with T2D and obesity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Zhang et al.)

It is important to improve the production of bioactive secondary products for drug development. The Escherichia coli-Streptomyces shuttle vector pSET152 and its derived vector pIB139 containing a strong constitutive promoter ermE p* are commonly used as integrative vectors in actinomycetes. Four new integrative vectors carrying the strong constitutive promoter kasO p*, hrdB p, SCO5768 p, and SP44, respectively, were constructed and proven to be functional in different mangrove-derived Streptomyces host strains by using kanamycin resistance gene neo as a reporter. Some biosynthetic genes of elaiophylins, azalomycin Fs, and armeniaspirols were selected and inserted into these vectors to overexpress in their producers including Streptomyces sp. 219807, Streptomyces sp. 211726, and S . armeniacus DSM 43125, resulting in an approximately 1.1-1.4-fold enhancement of the antibiotic yields.

This paper investigates the noise reduction performance of biomimetic hydrofoils with wavy leading edge and the corresponding mechanisms. We employ Large Eddy Simulation (LES) approach and permeable Ffowcs Williams-Hawkings (PFW-H) method to predict cavitation noise around the baseline and biomimetic hydrofoils. The results show that the wavy leading edge can effectively reduce the high-frequency noise, but has little effect on the low-frequency noise. Further analyses and discussions deal with the noise reduction mechanisms. The main source for the low-frequency noise is the cavity volume acceleration, while the wavy leading edge has little effect on it. The high-frequency noise sources, related to the surface pressure fluctuations and the turbulence characteristics, are significantly suppressed by the wavy leading edge, thus decreasing the high-frequency noise intensity. Our investigation indicates that the wavy leading edge has great prospects for cavitation noise reduction technique., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The ongoing global warming trajectory poses extensive challenges to plant ecosystems, with rubber plantations particularly vulnerable due to their influence on not only the longevity of the growth cycle and rubber yield, but also the complex interplay of carbon, water, and energy exchanges between the forest canopy and atmosphere. However, the response mechanism of phenology in rubber plantations to climate change remains unclear. This study concentrates on sub-optimal environment rubber plantations in Yunnan province, Southwest China. Utilizing the Google Earth Engine (GEE) cloud platform, multi-source remote sensing images were synthesized at 8-day intervals with a spatial resolution of 30-meters. The Normalized Difference Vegetation Index (NDVI) time series was reconstructed using the Savitzky-Golay (S-G) filter, coupled with the application of the seasonal amplitude method to extract three crucial phenological indicators, namely the start of the growing season (SOS), the end of the growing season (EOS), and the length of the growing season (LOS). Linear regression method, Pearson correlation coefficient, multiple stepwise regression analysis were used to extract of the phenology trend and find the relationship between SOS, EOS and climate factors. The findings demonstrated that 1) the phenology of rubber plantations has undergone dynamic changes over the past two decades. Specifically, the SOS advanced by 9.4 days per decade (R 2 = 0.42, p < 0.01), whereas the EOS was delayed by 3.8 days per decade (R 2 = 0.35, p < 0.01). Additionally, the LOS was extended by 13.2 days per decade (R 2 = 0.55, p < 0.01); 2) rubber phenology demonstrated a notable sensitivity to temperature fluctuations during the dry season and precipitation patterns during the rainy season. The SOS advanced 2.0 days (r =-0.19, p < 0.01) and the EOS advanced 2.8 days (r =-0.35, p < 0.01) for every 1°C increase in the cool-dry season. Whereas a 100 mm increase in rainy season precipitation caused the SOS to be delayed by 2.0 days (r = 0.24, p < 0.01), a 100 mm increase in hot-dry season precipitation caused the EOS to be advanced by 7.0 days (r =-0.28, p < 0.01); 3) rubber phenology displayed a legacy effect of preseason climate variations. Changes in temperature during the fourth preseason month and precipitation during the fourth and eleventh preseason months are predominantly responsible for the variation in SOS. Meanwhile, temperature changes during the second, fourth, and ninth preseason months are primarily responsible for the variation in EOS. The study aims to enhance our understanding of how rubber plantations respond to climate change in sub-optimal environments and provide valuable insights for sustainable rubber production management in the face of changing environmental conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lai, Chen, Yin, Wang, Wang, Yun, Lan, Wu, Yang and Kou.)

Objective: The prognostic utility of inflammatory markers in survival has been suggested in patients with cancer; however, evidence on their prognostic value in severely ill patients is very limited. We aimed to explore the prognostic value of cholinesterase (ChE), C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) in predicting mortality in patients from the intensive care unit (ICU)., Methods: Serum levels of ChE, CRP, IL-6 and PCT were measured in ICU patients from December 13 th , 2019 to June 28 th , 2022. We assessed the predictive power of ChE, CRP, IL-6, and PCT using the receiver operating characteristic (ROC) curves. Furthermore, we evaluated their diagnostic accuracy by comparing the areas under the ROC curve (AUCs) along with their corresponding 95% confidence intervals (CIs). The cut-off values were determined to dichotomise these biomarkers, which were then included in multivariable logistic regression models to examine their relationship with ICU mortality., Results: Among 253 ICU patients included in the study, 66 (26%) died during the ICU stay. The AUCs to predict ICU mortality were 0.643 (95% CI, 0.566-0.719), 0.648 (95% CI, 0.633-0.735), 0.643 (95% CI, 0.563-0.723) and 0.735 (95% CI, 0.664-0.807) for ChE, CRP, IL-6 and PCT, respectively. After adjusting for age, sex and disease severity, lower ChE level (<3.668 × 10 3 U L -1 ) and higher levels of CRP (>10.546 mg dL -1 ), IL-6 (>986.245 pg mL -1 ) and PCT (>0.505 μg L -1 ) were associated with higher mortality risk, with odd ratios of 2.70 (95% CI, 1.32-5.54), 4.99 (95% CI, 2.41-10.38), 3.24 (95% CI, 1.54-6.78) and 3.67 (95% CI, 1.45-9.95), respectively., Conclusion: ChE, CRP, IL-6 and PCT were independent ICU mortality risk factors in severely ill patients. Elevated PCT levels exhibited better predictive value than the other three biomarkers that were evaluated.

Aims: Visceral adiposity and skeletal muscle loss may be positively correlated with cardiometabolic outcomes. This study aimed to explore the associations between the visceral fat area to skeletal muscle mass ratio (VSR) and the risk of cardiometabolic diseases in a Chinese natural population., Materials and Methods: A total of 5158 participants were included in this study. Body composition, anthropometrical, and biochemical measurements were performed. Body composition was assessed via the direct segmental multi-frequency bioelectrical impedance analysis method. The associations between VSR and metabolic associated fatty liver disease (MAFLD), hyperglycemia, hypertension, dyslipidemia, and hyperuricemia were analysed., Results: With the increase of VSR by one quartile, the odds ratio (OR) increased significantly for all five cardiometabolic diseases in both genders (p trend  < 0.001). With regard to the highest versus the lowest quartile of VSR, the ORs for cardiometabolic diseases were significantly higher in women than in men. Restricted cubic splines showed that there were significant non-linear relationships between VSR and the risk of MAFLD, dyslipidemia, hyperglycemia, and hypertension in both genders (p for non-linearity <0.05). The risk was relatively flat until VSR reached 3.078 cm 2 /kg in men and 4.750 cm 2 /kg in women and started to increase rapidly afterwards. In men, however, the risk slowed down after the VSR value reached around 4 cm 2 /kg., Conclusions: VSR was positively associated with cardiometabolic diseases regardless of gender. As VSR increased, the risk of cardiometabolic diseases was significantly higher in women than in men., Trial Registration: www.chictr.org.cn (Registration number: ChiCTR2100044305)., (© 2022 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Background: The optimal dose of glucocorticoids for acute respiratory distress syndrome (ARDS) is uncertain. This study aimed to evaluate the effects of different doses of methylprednisolone on sepsis-induced acute lung injury (ALI) rats and a cohort of moderate and severe ARDS patients., Methods: ALI rats, challenged with lipopolysaccharide, were randomly received intraperitoneal injection of normal saline (model group) and different doses of methylprednisolone (0.5, 2, 8 mg/kg, named as low-, moderate- and high-dose group, respectively) for 5 days. The body weight changes of rats, inflammatory factors in bronchoalveolar lavage fluid (BALF), lung wet/dry ratio, histopathological score, and the mRNA expressions of glucocorticoid receptor α (GRα), GRβ and nuclear factor-κB (NF-κB) were measured. Forty moderate and severe ARDS patients were treated with standard of care or plus different doses of methylprednisolone (40, 80, 120 mg/day, named as low-, moderate- and high-dose group, respectively) for 5 days. Clinical outcomes were PaO 2 /FiO 2 ratio and C-reactive protein (CRP) level at day 5, intubation rate, hospital stay, 28-day mortality, and adverse events rate., Results: In animal experiment, different doses of methylprednisolone could increase the body weight of rats, and reduce inflammatory factors in BALF and the degree of lung injury compared with model group. The efficacy of methylprednisolone at moderate-dose was better than that at low-dose, but was equivalent to that at high-dose, which was consistent with the differential changes in the mRNA expression of GRα, GRβ and NF-κB. In clinical study, the moderate-dose group was associated with higher PaO 2 /FiO 2 ratio and lower CRP level. No significant difference in other clinical outcomes among groups was detected., Conclusions: This study showed that the efficacy of methylprednisolone in ARDS treatment was not always dose-dependent due to the differential regulation of related receptors. The moderate-dose of methylprednisolone may be the potential optimal dose for ARDS treatment, which needs to be further verified by larger clinical trials., (© 2022. The Author(s).)

Multi-ionization and subsequent Coulomb explosion (CE) of the N 2 O molecule irradiated by a linearly polarized 800 nm laser field is investigated by a reaction microscope, where a number of CE channels of N 2 O q+ with q ≤ 5 for two-body fragmentation and q ≤ 8 for three-body fragmentation were observed. For two-body CE, by analyzing the internuclear separations extracted from kinetic energy releases (KERs), dissociation branching fractions, and laser intensity dependence, interestingly, we found that fragmentation N 2 O 5+ → N 3+ + NO 2+ is produced directly from dissociating N 2 O 3+ via non-sequential stairstep ionization, whereas most of the others result from the sequential stairstep ionization. For three-body CE, 25 fragmentation channels of N 2 O q+ (q = 3-8) are distinguished in the present charge-encoded multi-photoion coincidence plot, and the concerted fragmentation mechanism is nominated in a typical Dalitz plot. With the help of the numerical computation with the measured KERs and momentum correlation angles, the geometric structures of molecular ions prior to fragmentation are reconstructed, which display the bending motion and simultaneous two-bond stretching before the CE. Increasing of the bond length for high charged N 2 O q+ indicates the dominating stairstep ionization in the three-body fragmentation.

The photoion-photoion coincidence (PIPICO) is a simple and effective approach for the selection of correlated fragments in a specific dissociating channel in molecules. We propose here a charge-encoded multi-photoion coincidence (cMUPICO) method, in analogy to traditional PIPICO, however in which the charge of individual fragments is taken into account. The cMUPICO method allows for clearly displaying coincident channels for dissociation channels containing three more fragments with unequal charge states, invisible in the traditional PIPICO. As a demonstration, three-body fragmentation dynamics of CO 2 in strong IR laser fields is analyzed, and 11 dissociation channels are effectively identified, five of which are first found with cMUPICO. The present results show that cMUPICO is a powerful and practical tool for distinguishing various dissociation channels with multiply charged multi-photoions.

Four mononuclear 9-coordinate Dy-based complexes, [Dy(HL 1 ) 2 (NO 3 ) 3 (CH 3 OH)] (1Dy), [Dy(HL 2 ) 2 (NO 3 ) 3 (H 2 O)] (2Dy), [Dy(HL 3 ) 3 (NO 3 ) 3 ]·CH 3 CN (3Dy), and [Dy(HL 4 ) 3 (NO 3 ) 3 ] (4Dy), have been constructed by neutral Schiff-base ligands (1-[ N -(4-R)aminomethylidene-2( 1H )-naphthalenone, R = -Cl (HL 1 ), -NO 2 (HL 2 ), -OCH 3 (HL 3 ), -I (HL 4 )). By tuning the terminal substituent group of HL ligands, the number of HL ligands coordinated to the central Dy 3+ ion unexpectedly varies from 2 to 3, and the local symmetry around the Dy 3+ ion reduces from D 3h to C s . Magnetic measurements reveal that 2Dy can display single-ion magnet (SIM) behavior in zero dc field, while 1Dy, 3Dy and 4Dy show field-induced slow magnetic relaxation. Ab initio calculations were employed to elucidate magnetic anisotropy in the complexes, including g -tensors, averaged transition magnetic moments and magnetic easy axes. The difference in magnetic behaviors of the four complexes can be ascribed to the terminal substituent effect of neutral Schiff-base ligands.

Patient transfer has always been a difficult problem, usually requiring multiple caregivers to work together, which is time consuming and can easily cause secondary injuries to the patient. In addition, with the crisis of COVID-19, the issue of patient transfer is even more critical, as caregivers are at a high risk of infection, causing significant damage to healthcare resources. In this paper, a patient transfer assist system named E-pat-plus (Easy Patient Transfer plus) has been proposed; it can assist caregivers in transferring patients, reduce direct contact between them, and avoid secondary injuries. In the mechanical structure of this apparatus, a novel five-gear assembly module and a synchronous belt pulley set are proposed; they are the key points to the basic functional realization of the device and can reduce the cost of the prototype. Furthermore, a fuzzy (proportion-integration-differentiation) PID-based cross-coupling control strategy is applied to the apparatus to ensure the stability and safety of the operation. Finally, some preliminary experiments, including current experiments and error experiments, are carried out to verify the reliability of the device and lay the foundation for clinical tests., Competing Interests: The authors declare that the authors do not have any competing financial or commercial interest., (Copyright © 2021 Yu Tian et al.)

The low-order harmonic generation induced by a strong laser field produces a bright, ultrashort, supercontinuum radiation ranging from the terahertz to ultraviolet band. By controlling the phase-delay and ellipticity of the bi-chromatic laser fields, the third harmonic generation is experimentally and theoretically investigated for elucidating the mechanism of the low-order harmonics. The third harmonic generation is found to be strongly suppressed in the counter-rotating bi-chromatic laser field due to the selection rule for harmonic emissions. The continuum-continuum transition in the strong field approximation is extended to explain the third harmonic generation as a function of the phase delay and ellipticity of the bi-chromatic laser fields. Compared with the semi-classical photocurrent model, the continuum-continuum transition on the basis of quantum-mechanical treatment achieves better agreement with the experimental observations. Our work indicates that the overlapping in continuum states via different quantum paths of a single electron plays a role in low-order harmonics generation under elliptical bi-chromatic laser fields.

Terahertz (THz) wave generation (TWG) in a dual-color laser is investigated with joint measurements between THz and third-harmonic generation, where the relative phase delay of dual-color fields is determined in situ in sub-wavelength accuracy, allowing for the clarification of the TWG mechanism in a direct comparison with various theoretical predictions. The delay- and polarization-dependent experiment validates that the continuum-continuum transition within the escaped electron wavepacket in the single atom gives birth to THz emission, while the bound energetic level does not contribute to TWG. TWG from atoms and molecules would provide an all-optical, vacuum-free, and ultrafast tool to record the spatiotemporal evolution of tunneling electron wavepackets.

The fibrotic response of vascular smooth muscle cells (VSMCs) takes responsibilities in atherosclerosis. Advanced glycation end products (AGEs) induce and promote the fibrotic responses of VSMCs. Matrine shows potent anti-fibrotic and cardio-protective effects. This study was aimed to investigate the underlying mechanisms of matrine's inhibitory effects on AGEs-induced VSMCs fibrotic responses. Cultured human coronary smooth muscle cells (HCSMCs) were pre-treated with matrine and exposed to AGEs. Specific siRNA was used to silence polymerase delta interacting protein 2 (Poldip2) expression. Sircol collagen assay was used to assess collagen content. Protein expression and phosphorylation levels were determined by Western blotting. Matrine pre-treatment significantly reduced collagen content, increased smooth muscle myosin heavy chain 11 (MYH11) and Poldip2 expression, decreased expressions of collagen I, β1-integrin, phsphoinositide-3-kinase (PI3K) and nuclear phosphorylated p70S6k, and reduced phosphorylation levels of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR) in HCSMCs exposed to AGEs in a concentration dependent manner. Specific siRNA effectively silenced Poldip2 expression and impaired matrine's effect on collagen content, expressions of MYH11, collagen I, β1-integrin, PI3K, nuclear p-p70S6k and phosphorylation levels of Akt and mTOR in HCSMCs exposed to AGEs. Matrine suppresses AGEs- induced fibrotic responses in HCSMCs via regulating Poldip2/mTOR signaling pathway., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Podoplanin (PDPN) is an important positive regulator of platelet aggregation and functions as a lymphatic endothelial marker. PDPN has been observed to be expressed in human tumor tissues and various cancer cell lines. In the present study, PDPN expression in patients with primary osteosarcoma was assessed at the mRNA and protein levels, and the associations between PDPN expression and pulmonary metastasis (PM) and prognosis were examined. Reverse transcription-quantitative PCR (RT-qPCR) analysis was used to detect the expression levels of PDPN in primary osteosarcoma tissues and paired normal bone tissues (n=20 pairs). In addition, immunohistochemical analysis of PDPN expression was performed in 168 paraffin-embedded osteosarcoma tissue specimens and 23 matched normal tissues. The RT-qPCR results revealed higher mRNA expression levels of PDPN in patients with PM compared with patients without PM. Further survival analyses identified Enneking stage and PM as two independent prognostic indicators. Finally, univariate analysis revealed that high PDPN protein expression was significantly associated with Enneking stage and PM in patients with osteosarcoma., (Copyright: © Wang et al.)

A low-energy, compact, and superconducting electron beam ion trap (the Shanghai-Wuhan EBIT or SW-EBIT) for extraction of highly charged ions is presented. The magnetic field in the central drift tube of the SW-EBIT is approximately 0.21 T produced by a pair of high-temperature superconducting coils. The electron-beam energy of the SW-EBIT is in the range of 30-4000 eV, and the maximum electron-beam current is up to 9 mA. Acting as a source of highly charged ions, the ion-beam optics for extraction is integrated, including an ion extractor and an einzel lens. A Wien filter is then used to measure the charge-state distribution of the extracted ions. In this work, the tungsten ions below the charge state of 15 have been produced, extracted, and analyzed. The charge-state distributions and spectra in the range of 530-580 nm of tungsten ions have been measured simultaneously with the electron-beam energy of 279 eV and 300 eV, which preliminarily indicates that the 549.9 nm line comes from W 14+ .

BACKGROUND The objective of this study was to study the anti-inflammatory effect and possibly involved molecular mechanisms of matrine on oxidized low-density lipoprotein (ox-LDL)-exposed macrophages. MATERIAL AND METHODS Cultured human macrophages (THP-1 cell line) were exposed to ox-LDL at final concentrations of 0, 25, 50, and 100 μg/mL. Several cells were then treated with matrine at serial diluted concentrations. 2,7-Dichlorodi-hydrofluorescein diacetate (DCFH-DA) staining was used to evaluate reactive oxygen species (ROS) production; a colorimetric method was used to determine the cellular antioxidant capacity; production of pro-inflammatory cytokines interleukin (IL)18 and tumor necrosis factor (TNF)alpha were determined by enzyme-linked immunosorbent assay (ELISA); and immunoblot assay was used to assess the relative protein phosphorylation and expression. RESULTS ox-LDL exposure significantly elevated intracellular ROS level and supernatant IL18 and TNFalpha concentrations, but impaired total antioxidant capacity (TAC) of macrophages. The relative phosphorylations of MAPK kinase kinases (MKK)6, MKK3, and p38 mitogen-activated protein kinases (MAPK) were increased by ox-LDL exposure. The expression levels of IL18 and TNFalpha were also increased in ox-LDL-treated macrophages. The matrine treatment reduced intracellular ROS level and supernatant IL18 and TNFalpha concentrations and increased TAC in a concentration- dependent manner. The relative phosphorylations of MKK6, MKK3, and p38 MAPK were reduced after matrine administration. Moreover, the expression levels of IL18 and TNFalpha were also decreased by matrine treatment, in a concentration-dependent manner. CONCLUSIONS ox-LDL increases inflammatory response in macrophages by activating the ROS-mediated MKKs/p38 MAPK-induced inflammatory signaling pathway. Matrine suppresses ox-LDL-induced inflammatory by inhibiting the MKKs/p38 MAPK signaling pathway.

Influenza viruses are responsible for seasonal epidemics and occasional pandemics, which cause significant morbidity and mortality. Although several drugs (adamantanes and neuraminidase inhibitors) are available in the market, the worldwide spread of drug-resistant influenza strains poses an urgent need for novel antiviral drugs. Artemisia rupestris L. is a folk medicine used to treat cold. In this paper, we structurally modified rupestonic acid, a bioactive component of A. rupestris, to synthesize a series of 2-substituted rupestonic acid methyl esters (3a-3o). Their structures were fully characterized by 1 H NMR, 13 C NMR, HRMS spectra. Among them, compounds 3b and 3c exhibited potent activities against influenza H1N1 with micromolar IC 50 values and might serve as new lead compounds for the treatment of influenza.

Serine protease inhibitor Kazal type 1 (SPINK1) plays a role in protecting the pancreas against premature activation of trypsinogen and is involved in cancer progression. SPINK1 promoted LAC cells growth, migration, and invasion. Mechanistically, we found that SPINK1 promoted LAC cells migration and invasion via up-regulating matrix metalloproteinase 12 (MMP12). We observed that SPINK1 expression was only up-regulated in lung adenocarcinoma (LAC) tissues, and was an independent prognostic factor for poor survival. Our results indicate that SPINK1 might be a potential biomarker for LAC that promotes progression by MMP12. [BMB Reports 2018; 51(12): 648-653].

The efficient conversion of carbohydrates to 5-hydroxymethylfurfural (5-HMF) under mild conditions represents a very attractive and promising method of producing important building blocks. In this work, niobium phosphotungstates, with Nb/P molar ratios of 0.6, 1.0, 2.0 and 4.0 (NbPW-06, NbPW-1, NbPW-2, and NbPW-4, respectively) have been prepared by a facile, one-pot, alcohol-mediated thermal process and used for the direct conversion of fructose to 5-HMF. By adding a certain amount of Nb, the surface of the catalyst became enriched in P, and this enrichment was associated with the presence of surface P-OH groups that offered Brønsted acid sites that can activate superficial hydrogen species to facilitate 5-HMF generation. Pyridine-FTIR confirmed the presence of Brønsted and Lewis acid sites, which might play important roles in the dehydration of fructose to 5-HMF. Furthermore, polar aprotic solvents were well-suited for the conversion, and higher yields of 5-HMF were obtained in polar aprotic solvents than in nonpolar solvents. A 5-HMF yield of 96.7% with complete fructose consumption was obtained over NbPW-06 in DMSO at 80 °C after 90 min. In addition, NbPW-06 could be recycled several times without a significant decrease in the catalytic activity. A catalytic mechanism for this reaction was proposed. Moreover, this catalytic system can also be utilized for the dehydration of sucrose and inulin to 5-HMF in satisfactory yields. This study establishes an important platform for the further design of Nb-containing catalysts for the production of 5-HMF from carbohydrates under mild conditions., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The lower limb rehabilitation robot is an application of robotic technology for stroke people with lower limb disabilities. A new applicable and effective sitting/lying lower limb rehabilitation robot (LLR-Ro) is proposed, which has the mechanical limit protection, the electrical limit protection, and the software protection to prevent the patient from the secondary damage. Meanwhile, as a new type of the rehabilitation robots, its hip joint rotation ranges are different in the patient sitting training posture and lying training posture. The mechanical leg of the robot has a variable workspace to work in both training postures. So, if the traditional mechanical limit and the electrical limit cannot be used in the hip joint mechanism design, a follow-up limit is first proposed to improve the compatibility of human-machine motion. Besides, to eliminate the accident interaction force between the patient and LLR-Ro in the process of the passive training, an amendment impedance control strategy based on the position control is proposed to improve the compliance of the LLR-Ro. A simulation experiment and an experiment with a participant show that the passive training of LLR-Ro has compliance., Competing Interests: The authors declare that they have no conflicts of interest., (© 2017 Yongfei Feng et al.)

The lower limb rehabilitation robot is an application of robotic technology for stroke people with lower limb disabilities. A new applicable and effective sitting/lying lower limb rehabilitation robot (LLR-Ro) is proposed, which has the mechanical limit protection, the electrical limit protection, and the software protection to prevent the patient from the secondary damage. Meanwhile, as a new type of the rehabilitation robots, its hip joint rotation ranges are different in the patient sitting training posture and lying training posture. The mechanical leg of the robot has a variable workspace to work in both training postures. So, if the traditional mechanical limit and the electrical limit cannot be used in the hip joint mechanism design, a follow-up limit is first proposed to improve the compatibility of human-machine motion. Besides, to eliminate the accident interaction force between the patient and LLR-Ro in the process of the passive training, an amendment impedance control strategy based on the position control is proposed to improve the compliance of the LLR-Ro. A simulation experiment and an experiment with a participant show that the passive training of LLR-Ro has compliance.

The tumor suppressor, cylindromatosis (CYLD), is a negative regulator of NF-κB signaling by removing lysine 63-linked ubiquitin chains from multiple NF-κB signaling components, including TRAF2, TRAF6, and NEMO. How CYLD itself is regulated, however, remains yet to be characterized. In this study, we present the first evidence that UV irradiation is able to induce CYLD translocation from the cytoplasm to microtubules and that the cytoskeleton-associated CYLD is subject to posttranslational modification and degradation in a proteasome-independent manner. By immunostaining, we found that CYLD displayed microtubule-like filament localization under ultraviolet (UV) irradiation. Further studies revealed that the cytoskeleton-associated CYLD underwent posttranslational modification, which in turn contributed to CYLD degradation in an unknown manner, distinct from proteasome-mediated degradation under normal conditions. Collectively, our data suggest that UV-induced CYLD degradation might serve as an underlying mechanism for UV-induced NF-κB pathway activation.

Tubulin is known to undergo unique post-translational modifications (PTMs), such as detyrosination and polyglutamylation, particularly in the unstructured carboxy-terminal tails (CTTs). However, more conventional PTMs of tubulin and their roles in the regulation of microtubule properties and functions remain poorly defined. Here, we report the comprehensive profiling of tubulin phosphorylation, acetylation, ubiquitylation, and O-GlcNAcylation in HeLa cells with a proteomic approach. Our tubulin-targeted analysis has identified 80 residues bearing single or multiple conventional PTMs including 24 novel PTM sites not covered in previous global proteomic surveys. By using a series of PTM-deficient or PTM-mimicking mutants, we further find that tubulin phosphorylation and acetylation play important roles in the control of microtubule assembly and stability. In addition, these tubulin PTMs have distinct effects on the retrograde transport of adenoviruses along microtubules. These findings thus enlarge the repertoire of tubulin PTMs and foster our understanding of their versatile roles in the regulation of microtubule dynamics and cellular functions.

The Tat protein of HIV-1 has several well-known properties, such as nucleocytoplasmic trafficking, transactivation of transcription, interaction with tubulin, regulation of mitotic progression, and induction of apoptosis. Previous studies have identified a couple of lysine residues in Tat that are essential for its functions. In order to analyze the functions of all the lysine residues in Tat, we mutated them individually to alanine, glutamine, and arginine. Through systematic analysis of the lysine mutants, we discovered several previously unidentified characteristics of Tat. We found that lysine acetylation could modulate the subcellular localization of Tat, in addition to the regulation of its transactivation activity. Our data also revealed that lysine mutations had distinct effects on microtubule assembly and Tat binding to bromodomain proteins. By correlation analysis, we further found that the effects of Tat on apoptosis and mitotic progression were not entirely attributed to its effect on microtubule assembly. Our findings suggest that Tat may regulate diverse cellular activities through binding to different proteins and that the acetylation of distinct lysine residues in Tat may modulate its interaction with various partners.

Objective: Discuss the effect degree and phase of microwave radiation on the hematopoietic system in rats, and to provide basis for human health life., Methods: Use the methods of blood cell analysis and Wright-Gimsa stain to analyse the peripheral blood cell and marrow smear of the different time (1d, 7d and 14d) Wistar rats that exposured by different radiation dose., Results: Compare with the untreated control group, various cell parameters of blood in the microwave radiation rats had different changes, and their marrow smear was obviously destroyed;especially the group treated with 200 mW/cm2 microwave exposure had more significant change at seven-day. For the 14d group,the other hematological parameters all return to control except WBC, LY#, MID# and N# increase,PLT and PCT remain lower., Conclusion: Microwave radiation can influence hematological system of rats, and with the radiation dose increased, the effect is more significant.