Exploring Biomolecular Conformational Dynamics with Polarizable Force Field AMOEBA and Enhanced Sampling Method Milestoning.

Conformational dynamics play a crucial role in determining the behavior of the biomolecules. Polarizable force fields, such as AMOEBA, can accurately capture electrostatic interactions underlying the conformational space. However, applying a polarizable force field in molecular dynamics (MD) simulations can be computationally expensive, especially in studying long-time-scale dynamics. To overcome this challenge, we incorporated the AMOEBA potential with Milestoning, an enhanced sampling method in this work. This integration allows us to efficiently sample the rare and important conformational states of a biomolecule by using many short and independent molecular dynamics trajectories with the AMOEBA force field. We applied this method to investigate the conformational dynamics of alanine dipeptide, DNA, and RNA A-B form conversion. Well-converged thermodynamic and kinetic properties were obtained, including the free energy difference, mean first passage time, and critical transitions between states. Our results demonstrate the power of integrating polarizable force fields with enhanced sampling methods in quantifying the thermodynamic and kinetic properties of biomolecules at the atomic level.

Associations between regular physical exercise and physical, emotional, and cognitive health of older adults in China: an 8-year longitudinal study with propensity score matching.

Background: The importance of healthy aging is growing in China as it has the largest number of older adults in the world and is one of the fastest-aging countries. This study aimed to examine the predictive value of regular physical exercise in relation to the physical, emotional, and cognitive health among samples of adults aged ≥60 years in China during an 8-year period. Methods: A total of 10,691 older adults were extracted from two waves of national data from the China Family Panel Studies in 2010 and 2018. To minimize the impact of selection bias on the findings, a longitudinal propensity score matching (LPSM) method was used to examine the relationships between regular physical exercise and emotional health (depression), between regular physical exercise and physical health (instrumental activities of daily living), and between regular physical exercise and cognitive health (cognitive ability) of older adults. After LPSM, 856 older adults were included in the study. In the regular physical exercise group, the average age of participants at baseline year was 65.67 years, with an average age of 65.90 years for 238 men and 65.45 years for 190 women, and in the non-physical exercise group, their average age at baseline year was 65.70 years, with an average age of 65.45 years for 253 men and 65.98 years for 175 women. Results: LPSM indicated that regular physical exercise has been found to be effective in improving physical function and reducing depressive symptoms in old adults, even after controlling for background differences. However, the sensitivity analysis suggests that the positive association between regular physical exercise and cognitive function may not be sufficiently valid. Conclusion: The findings of this study indicate that engaging in long-term structured and repetitive physical exercise can have a significant positive effect on reducing depressive symptoms and improving the physical function of older adults. As a result, incorporating regular physical exercise into the lifestyle of older adults is recognized as an effective strategy for promoting healthy aging and reducing the strain on public health resources.

Fruit freshness detection based on multi-task convolutional neural network.

Background: Fruit freshness detection by computer vision is essential for many agricultural applications, e.g., automatic harvesting and supply chain monitoring. This paper proposes to use the multi-task learning (MTL) paradigm to build a deep convolutional neural work for fruit freshness detection. Results: We design an MTL model that optimizes the freshness detection (T1) and fruit type classification (T2) tasks in parallel. The model uses a shared CNN (convolutional neural network) subnet and two FC (fully connected) task heads. The shared CNN acts as a feature extraction module and feeds the two task heads with common semantic features. Based on an open fruit image dataset, we conducted a comparative study of MTL and single-task learning (STL) paradigms. The STL models use the same CNN subnet with only one specific task head. In the MTL scenario, the T1 and T2 mean accuracies on the test set are 93.24% and 88.66%, respectively. Meanwhile, for STL, the two accuracies are 92.50% and 87.22%. Statistical tests report significant differences between MTL and STL on T1 and T2 test accuracies. We further investigated the extracted feature vectors (semantic embeddings) from the two STL models. The vectors have an averaged 0.7 cosine similarity on the entire dataset, with most values lying in the 0.6-0.8 range. This indicates a between-task correlation and justifies the effectiveness of the proposed MTL approach. Conclusion: This study proves that MTL exploits the mutual correlation between two or more relevant tasks and can maximally share their underlying feature extraction process. we envision this approach to be extended to other domains that involve multiple interconnected tasks.

Application of atmospheric cold plasma for zearalenone detoxification in cereals: Kinetics, mechanisms, and cytotoxicity analysis.

INTRODUCTION: Zearalenone (ZEN) is one of the most widely contaminated mycotoxins in world, posing a severe threat to human and animal health. Atmospheric cold plasma (ACP) holds great penitential in mycotoxin degradation. OBJECTIVES: This study aimed to investigate the degradation efficiency and mechanisms of ACP on ZEN as well as the cytotoxicity of ZEN degradation products by ACP. Additionally, this study also investigated the degradation efficiency of ACP on ZEN in cereals and its effect on cereal quality. METHODS: The degradation efficiency and products of ZEN by ACP was analyzed by HPLC and LC-MS/MS. The human normal liver cells and mice were employed to assess the cytotoxicity of ZEN degradation products. The ZEN artificially contaminated cereals were used to evaluate the feasibility of ACP detoxification in cereals. RESULTS: The results showed that the degradation rate of ZEN was 96.18 % after 30-W ACP treatment for 180 s. The degradation rate was dependent on the discharge power, and treatment time and distance. Four major ZEN degradation products were produced after ACP treatment due to the oxidative destruction of CC double bond, namely C18H22O7 (m/z = 351.19), C18H22O8 (m/z = 367.14), C18H22O6 (m/z = 335.14), and C17H20O6 (m/z = 321.19). L02 cell viability was increased from 52.4 % to 99.76 % with ACP treatment time ranging from 0 to 180 s. Mice results showed significant recovery of body weight and depth of colonic crypts as well as mitigation of glomerular and liver damage. Additionally, ACP removed up to 50.55 % and 58.07 % of ZEN from wheat and corn. CONCLUSIONS: This study demonstrates that ACP could efficiently degrade ZEN in cereals and its cytotoxicity was significantly reduced. Therefore, ACP is a promising effective method for ZEN detoxification in cereals to ensure human and animal health. Future study needs to develop large-scale ACP device with high degradation efficiency.

Direct Synthesis of α- and ß-2'-Deoxynucleosides with Stereodirecting Phosphine Oxide via Remote Participation.

2'-Deoxynucleosides and analogues play a vital role in drug development, but their preparation remains a significant challenge. Previous studies have focused on ß-2'-deoxynucleosides with the natural ß-configuration. In fact, their isomeric α-2'-deoxynucleosides also exhibit diverse bioactivities and even better metabolic stability. Herein, we report that both α- and ß-2'-deoxynucleosides can be prepared with high yields and stereoselectivity using a remote directing diphenylphosphinoyl (DPP) group. It is particularly efficient to prepare α-2'-deoxynucleosides with an easily accessible 3,5-di-ODPP donor. Instead of acting as a H-bond acceptor on a 2-(diphenylphosphinoyl)acetyl (DPPA) group in our previous studies for syn-facial O-glycosylation, the phosphine oxide moiety here acts as a remote participating group to enable highly antifacial N-glycosylation. This proposed remote participation mechanism is supported by our first characterization of an important 1,5-briged P-heterobicyclic intermediate via variable-temperature NMR spectroscopy. Interestingly, antiproliferative assays led to a α-2'-deoxynucleoside with IC50 values in the low micromole range against central nervous system tumor cell lines SH-SY5Y and LN229, whereas its ß-anomer exhibited no inhibition at 100 µM. Furthermore, the DPP group significantly enhanced the antitumor activities by 10 times.

Human emissions of size-resolved fluorescent bioaerosols in control situations.

Human bioaerosols contribute significantly to indoor air quality. This study used a Wideband Integrated Bioaerosol Sensor (WIBS-4A) instrument for real-time measurement of particle size distribution and count to differentiate fluorescent bioaerosols from non-fluorescent aerosols. Through an experiment involving 12 subjects (six men and six women) wearing standard cotton clothing in a 2 m × 2 m × 2 m environmental chamber, we established a quantitative method to obtain the bioaerosol emission rate of a single subject, aiming to explore the effects of masks and sex on bioaerosol emissions from different individuals. The mean emission rates of fluorescent bioaerosols in the particle size ranges of 0.5-2.5 µm and 2.5-10 µm were 3.192±2.11×104 counts/(person·h) and 13.98±9.34×104 counts/(person·h), respectively. A comparison between those wearing and not wearing masks revealed no significant differences in the emissions of fluorescent bioaerosols. This suggests respiratory sources may not significantly impact the emissions of fluorescent bioaerosols from individuals under seated breathing conditions. Significant disparities in the fluorescent bioaerosol emission rates of different biological sexes were observed through independent sample analysis. Males exhibited 41 % and 15 % higher emission rates than females for particle size ranges of 0.5-2.5 µm and 2.5-10 µm, respectively, possibly because of different metabolic rates. A significant correlation between metabolic rates and fluorescent bioaerosols (sig = 0.044 < 0.05) was observed in all the subjects. These findings underscore the individual variations that affect bioaerosol emission rates. The data provided by this study will facilitate further analysis of the on-site measured data and source analysis.

Kinetic Process with Anti-Frenkel Disorder in a CsPbI3 Perovskite.

Halide perovskites are rich in ionic diffusion phenomena due to their low activation energy. The soft lead iodide lattice can, in theory, endow the system with more complex defect collaborative motions. In this work, we systematically investigated the hopping mechanics of iodide interstitials with respect to various defect behaviors, such as anti-Frenkel disorder creation and annihilation. We found that the existence of iodide vacancies and interstitials can effectively lower the creation barrier of additional anti-Frenkel disorder in the halide perovskite. The free energy barriers for generating additional Frenkel defect pairs vary from 0.25 to 0.43 eV, in the proximity of those of the original iodide defects at 300 K. This finding suggests that the spontaneous creation of a specific level of anti-Frenkel disorder facilitates long-range annihilation and defect hopping processes.

Synthesis and Structural Revision of a Natural Tetrasaccharide from Starfish Asterias rollestoni Bell.

Starfish provide important saponins with diverse bioactivities as the secondary metabolites, among which 2-O-glycosylated glycosides are commonly found. Preparation of those 1,2-trans 2-O-glycosylated glycosides usually relies on 2-O-acyl participation requiring the selective installation and cleavage of 2-O-acyl groups. A convergent synthesis using 2-O-glycosylated oligosaccharide donors would be more straightforward but also pose greater challenges. Herein, we report a convergent synthesis of a distinctive tetrasaccharide isolated from starfish Asterias rollestoni Bell. Dual 2-(diphenylphosphinoyl)acetyl (DPPA) groups at O3 and O4 on galactose moiety led to high ß-selectivities (ß/α=12/1 or ß only) in the challenging [2+2] glycosylation, giving the desired tetrasaccharides in >90 % yields from the 2-O-glycosylated disaccharide donors. These synthetic studies have also unambiguously revised the structure of these natural tetrasaccharides. This work would facilitate further studies on new inhibitors of α-glucosidase as hypoglycemic drugs.

Toward stabilization of formamidinium lead iodide perovskites by defect control and composition engineering.

Phase instability poses a serious challenge to the commercialization of formamidinium lead iodide (FAPbI3)-based solar cells and optoelectronic devices. Here, we combine density functional theory and machine learning molecular dynamics simulations, to investigate the mechanism driving the undesired α-δ phase transition of FAPbI3. Prevalent iodine vacancies and interstitials can significantly expedite the structural transition kinetics by inducing robust covalency during transition states. Extrinsically, the detrimental roles of atmospheric moisture and oxygen in degrading the FAPbI3 perovskite phase are also rationalized. Significantly, we discover the compositional design principles by categorizing that A-site engineering primarily governs thermodynamics, whereas B-site doping can effectively manipulate the kinetics of the phase transition in FAPbI3, highlighting lanthanide ions as promising B-site substitutes. A-B mixed doping emerges as an efficient strategy to synergistically stabilize α-FAPbI3, as experimentally demonstrated by substantially higher initial optoelectronic characteristics and significantly enhanced phase stability in Cs-Eu doped FAPbI3 as compared to its Cs-doped counterpart. This study provides scientific guidance for the design and optimization of long-term stable FAPbI3-based solar cells and other optoelectronic devices through defect control and synergetic composition engineering.

A lightweight network for traffic sign recognition based on multi-scale feature and attention mechanism.

Traffic sign recognition is an important part of intelligent transportation system. It uses computer vision and traffic sign recognition technology to detect and recognize traffic signs on the road automatically. In this paper, we propose a lightweight model for traffic sign recognition based on convolutional neural networks called ConvNeSe. Firstly, the feature extraction module of the model is constructed using the Depthwise Separable Convolution and Inverted Residuals structures. The model extracts multi-scale features with strong representation ability by optimizing the structure of convolutional neural networks and fusing of features. Then, the model introduces Squeeze and Excitation Block (SE Block) to improve the attention to important features, which can capture key information of traffic sign images. Finally, the accuracy of the model in the German Traffic Sign Recognition Benchmark Database (GTSRB) is 99.85%. At the same time, the model has good robustness according to the results of ablation experiments.

Dexmedetomidine versus midazolam as intranasal premedication for intravenous deep sedation in pediatric dental treatment.

Background/purpose: Optimal sedation management for pediatric dental treatment demands special focus as it's tubeless and shares a same oral space. The study was to evaluate dexmedetomidine compared to midazolam for intranasal premedication in pediatric dental treatment under intravenous deep sedation. Materials and methods: A hundred children aged 3-7 years scheduled for elective dental treatment under intravenous deep sedation anesthesia were enrolled, of whom 50 children (Group D) were intranasally premedicated with 2.0 µg/kg dexmedetomidine and the remaining 50 children (Group M) received traditional 0.2 mg/kg midazolam. Acceptance rate of venipuncture was regarded as the primary endpoint. Results: The acceptance rate of venipuncture in Group D and Group M were 76% versus 52%, respectively (P = 0.021). More children in Group M complained about bitter/sour taste than Group D (62% vs. 8%, P < 0.001). Intraoperatively, children in Group M were found to have more choking cough than Group D (30% vs. 9%, P = 0.003), and patients in Group M required more suction (18 [36%] in Group M vs. 4 [8%] in Group D, P = 0.001). There were no significant differences between the groups in the incidences of temporal hypoxemia (SpO2 ≤ 90%), however, two children in Group M experienced hypoxemia over 10 s. Conclusion: Compared to the 0.2 mg/kg midazolam, children premedicated with 2.0 µg/kg intranasal dexmedetomidine showed superior venipuncture acceptance, had less intraoperative choking cough and required fewer suction. It seems to be a good alternative to midazolam as premedication for deep sedation in pediatric dental treatment.

Efficacy of intranasal administration of dexmedetomidine in combination with midazolam for sedation in infant with cleft lip and palate undergoing CT scan: a randomized controlled trial.

BACKGROUND: There is a great challenge to sedation for infants with cleft lip and palate undergoing CT scan, because there is the younger age and no consensus on the type, dosage, and route of drug administration. OBJECTIVE: This study aimed to evaluate the efficacy of intranasal administration of dexmedetomidine combined with midazolam as a sedative option for infants with cleft lip and palate under imaging procedures. METHODS: Infants scheduled for cleft lip and palate repair surgery were randomly assigned to the IND group (intranasal dexmedetomidine 2 µg/kg alone) and the INDM group (intranasal dexmedetomidine 2 µg/kg combined with midazolam 0.05 mg/kg). The primary outcome was the proportion of infants underwent successful computed tomography (CT) scans under intranasal sedation. The secondary outcomes included onset time and duration of sedation, recovery time, Ramsay sedation scale, hemodynamic parameters during sedation, and adverse events. Data analyses involved the unpaired t-test, the repeated-measures analysis of variance test, and the continuity correction χ2 test. RESULTS: One hundred five infants were included in the analysis. The proportion of infants underwent successful CT scans under sedation was significantly greater in the INDM group than in the IND group (47 [95.9%] vs. 45 [80.4%], p = 0.016). Additionally, the INDM group had a shorter onset time and a longer duration of sedation statistically (12 [8.5, 17] min vs. 16 [12, 20] min, p = 0.001; 80 [63.6, 92.5] min vs. 68.5 [38, 89] min, p = 0.014, respectively), and their recovery time was significantly longer (43 [30, 59.5] min vs. 31.5 [20.5, 53.5] min, p = 0.006). The difference in Ramsay sedation scale values 20 min after administration was statistically significant between the groups. No statistically significant difference was found between the groups in changes in heart rate and respiratory rate. CONCLUSION: Intranasal administration of dexmedetomidine in combination with midazolam resulted in higher sedation success in comparison with sole dexmedetomidine. However, it has a relatively prolonged duration of sedation and recovery time. TRIAL REGISTRATION: ChiCTR2100049122, Clinical trial first registration date: 21/07/2021.

Recent advances in the degradation efficacy and mechanisms of mycotoxins in food by atmospheric cold plasma.

Food contaminated by mycotoxins has become a worldwide public problem with political and economic implications. Although a variety of traditional methods have been used to eliminate mycotoxins from agri-foods, the results have been somewhat less than satisfactory. As an emerging non-thermal processing technology, atmospheric cold plasma (ACP) has great potential for food decontamination. Herein, this review mainly presents the degradation efficiency of ACP on mycotoxins in vitro and agri-foods as well as its possible degradation mechanisms. Meanwhile, ACP effects on food quality, factors affecting the degradation efficiency and the toxicity of degradation products are also discussed. According to the literatures, ACP could efficiently degrade many mycotoxins (e.g., aflatoxin, deoxynivalenol, zearalenone, ochratoxin A, fumonisin, and T-2 toxin) both in vitro and various foods (e.g., hazelnut, peanut, maize, rice, wheat, barley, oat flour, and date palm fruit) with little effects on the nutritional and sensory properties of food. The degradation efficacy was dependent on many factors including ACP treatment parameter, working gas, mycotoxin property, and food substrate. The mycotoxin degradation by ACP was mainly attributed to the reactive oxygen and nitrogen species in ACP, which can damage the chemical bonds of mycotoxins, consequently reducing the toxicity of mycotoxins.

Intelligent wound dressing for simultaneous in situ detection and elimination of pathogenic bacteria.

Wound infections hinder the healing process and potentially result in life-threatening complications, which urgently require rapid and timely detection and treatment pathogens during the early stages of infection. Here, an intelligent wound dressing was developed to enable in situ detection and elimination of pathogenic bacteria through a combination of point-of-care testing and antibacterial photodynamic therapy technology. The dressing is an injectable hydrogel composed of carboxymethyl chitosan and oxidized sodium alginate, with addition of 4-methylumphulone beta-D-glucoside (MUG) and up-converted nanoparticles coated with titanium dioxide (UCNPs@TiO2). The presence of bacteria can be visually detected by monitoring the blue fluorescence of 4-methylumbellione, generated through the reaction between MUG and the pathogen-associated enzyme. The UCNPs@TiO2 photosensitizers were synthesized and demonstrated high antibacterial activity through the generation of reactive oxygen species when exposed to near-infrared irradiation. Meanwhile, a smartphone-based portable detection system equipped with a self-developed Android app was constructed for in situ detection of pathogens in mere seconds, detecting as few as 103 colony-forming unit. Additionally, the dressing was tested in a rat infected wound model and showed good antibacterial activity and pro-healing ability. These results suggest that the proposed intelligent wound dressing has potential for use in the diagnosis and management of wound infections. STATEMENT OF SIGNIFICANCE: An intelligent wound dressing has been prepared for simultaneous in situ detection and elimination of pathogenic bacteria. The presence of bacteria can be visually detected by tracking the blue fluorescence of the dressing. Moreover, a smartphone-based detection system was constructed to detect and diagnose pathogenic bacteria before reaching the infection limit. Meanwhile, the dressing was able to effectively eliminate key pathogenic bacteria on demand through antibacterial photodynamic therapy under NIR irradiation. The proposed intelligent wound dressing enables timely detection and treatment of infectious pathogens at an early stage, which is beneficial for wound management.

Lidocaine Spray for Acute Postsurgical Pain Control After Posterior Pharyngeal Flap Surgery.

OBJECTIVES: This study evaluated the use of lidocaine spray for acute postsurgical pain control after posterior pharyngeal flap surgery. METHODS: Fifty patients aged 4 to 14 years who were scheduled to undergo elective posterior pharyngeal flap surgery were randomized to receive 2.4% lidocaine spray (Group L) or an identical volume of placebo spray (Group C) on the surgical field at the end of the surgery. The primary outcome was the maximum postoperative pain score in the postanesthesia care unit. RESULTS: The maximum pain score in Group L was significantly lower than that in Group C (p = 0.001). The incidence of moderate-to-severe pain in the postanesthesia care unit was significantly lower in Group L than that in Group C (p < 0.001). In the postanesthesia care unit, more patients in Group C were prescribed rescue analgesics (p < 0.001). The time to the first rescue analgesic was also significantly shorter in Group L (p < 0.001). The incidence and maximum score of emergence agitation were lower in Group L than in Group C. Compared with Group C, Group L showed earlier postoperative fluid intake (p = 0.001). Moreover, the score for parental satisfaction with pain control was higher in Group L than in Group C (p < 0.001). CONCLUSIONS: Our findings indicated that the use of 2.4% lidocaine aerosol spray on the surgical site at the end of the surgery could produce good analgesia for acute postoperative pain, reduce the incidence and severity of EA, and shorten the time to restore fluid intake. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:2438-2443, 2024.

Increased NAD+ levels protect female mouse reproductive system against zearalenone-impaired glycolysis, lipid metabolism, antioxidant capacity and inflammation.

The reproductive system is a primary target organ for zearalenone (ZEN, a widespread fusarium mycotoxin) to exert its toxic effects, including decreased antioxidant capacity and aggravated inflammatory response. These ZEN-induced reproductive abnormalities are partially caused by the declining levels of nicotinamide adenine dinucleotide (NAD+), which results in an imbalance in lipid/glucose metabolism. Accordingly, the present study aimed to investigate whether supplements of nicotinamide mononucleotide (NMN, a NAD+ precursor) in female mice could protect against ZEN-induced reproductive toxicity. In this study, thirty female mice were randomly divided into three groups that were intragastrically administered with i) 0.5% DMSO (the Ctrl group), ii) 3 mg/(kg bw.d) ZEN (the ZEN group), or iii) ZEN + 500 mg/(kg bw.d) NMN (the ZEN/NMN group) for two weeks. The results revealed that, compared with the Ctrl group, animals exposed to ZEN exhibited reproductive toxicity, such as decreased antioxidant capacity and aggravated inflammatory response in reproductive tissues. These effects were strongly correlated with lower activities in key glycolytic enzymes (e.g., ALDOA and PGK), but increased expressions in key lipid-synthesis genes (e.g., LPIN1 and ATGL). These changes contribute to lipid accumulation, specifically for diacylglycerols (DAGs). Furthermore, these ZEN-induced changes were linked with disturbed NAD+ synthesis/degradation, and subsequently decreased NAD+ levels. Notably, NMN supplements in mice protected against these ZEN-induced reproductive abnormalities by boosting NAD+ levels. Herein, the present findings demonstrate that potential strategies to enhance NAD+ levels can protect against ZEN-induced reproductive toxicity.

Investigating the spatial distribution of volatile organic compounds in aircraft cabins from various emission sources.

Volatile organic compounds (VOCs) significantly affect the air quality in aircraft cabins, consequently affecting passenger health and comfort. Although VOC emission sources and their contributions have been studied extensively, the distribution characteristics of VOCs originating from diverse sources within cabins have received limited attention, and the correlation between VOC sources and concentrations in passenger breathing zones remains largely unexplored. To fill this knowledge gap, the concentration field of VOCs was investigated using a computational fluid dynamics model, and the results were experimentally validated in a typical single-aisle aircraft cabin with seven seat rows. The diffusion characteristics of different VOCs emitted by four typical sources in aircraft cabins (floors, human surfaces, seats, and respiratory sources) were analyzed and compared. The distribution of VOCs emitted by different sources was nonuniform and could be classified into two distinct categories. When the emission intensities of all sources were equal, the average concentration of VOCs emitted from the floor source were considerably lower in the passenger breathing zone (4.01 µg/m³) than those emitted from the human surface, seat, and respiratory sources, which exhibited approximately equal concentrations (6.82, 6.90, and 7.29 µg/m³, respectively). The analysis highlighted that the simplified lumped-parameter method could not accurately estimate the exposure concentrations within an aircraft cabin. To address this issue, we propose a correction method based on the emission intensity of each VOC source. This study provides critical insights into the diffusion characteristics of VOCs within aircraft cabins and VOC emissions from various sources.

Surface Performance of Nano-CrN/TiN Multi-Layered Coating on the Surface of Ti Alloy.

Surface coating has been widely used to ameliorate the surface properties of Ti alloys. In this study, high-power pulsed magnetically controlled sputtering technology was used to successfully prepare a nano-CrN/TiN multi-layered coating on the surface of a TC4 Ti alloy. The surface of the obtained coating was uniform, dense, and free of obvious defects. With the decrease in modulation period, the optimal growth of the nano-CrN/TiN multi-layered coating was changed from a (220) crystal surface to (111) and a (200) crystal surface. Compared to the single-layered CrN or TiN coating, the nano-multi-layered coating had higher hardness and lower wear rate. Furthermore, the hardness and the wear resistance increased with the decrease in the modulation period. This presented an optimal modulation period of 6 nm. Meanwhile, the resistance of the obtained coating to high-temperature oxidation at 800 °C was also significantly improved.

Effects of dapagliflozin monotherapy and combined aerobic exercise on skeletal muscle mitochondrial quality control and insulin resistance in type 2 diabetes mellitus rats.

Type 2 diabetes mellitus (T2DM) is a prevalent, chronic metabolic disease. Sodium-glucose cotransporter-2 (SGLT2) inhibitors and aerobic exercise (AE) have shown promise in mitigating insulin resistance (IR) and T2DM. This study investigated the effects of dapagliflozin (Dapa) monotherapy and combined AE on mitochondrial quality control (MQC) in skeletal muscle and IR in T2DM rats. T2DM rats, induced by a high-fat diet/streptozotocin model, were randomly assigned to the following groups: T2DM+vehicle group (DMV), T2DM rats treated with Dapa (DMDa, 10 mg/kg/d), T2DM rats subjected to combined Dapa treatment and AE (DMDa+AE), and the standard control group (CON). Blood and skeletal muscle samples were collected after 6 weeks of intragastric administration and treadmill exercise. The results showed that DMDa monotherapy could reduce the accumulation of white adipose tissue and skeletal muscle lipid droplets and improve HOMA-IR. While the combined AE led to further reductions in subcutaneous white adipose tissue and fasting glucose levels, it did not confer additional benefits in terms of HOMA-IR. Furthermore, Dapa monotherapy enhanced skeletal muscle mitochondrial biogenesis (PGC-1α, NRF1, TFAM, and COX IV), mitochondrial dynamics (OPA1, DRP1, and MFN2), and mitophagy (PGAM5 and PINK1) related protein levels. Nevertheless, the combination of Dapa with AE treatment did not yield an additive effect. In conclusion, this study highlights the potential of SGLT2 inhibitors, specifically Dapa, in ameliorating IR and maintaining MQC in skeletal muscle in rats with T2DM. However, combined AE did not produce an additive effect, indicating the need for further research.

Past climate cooling and orogenesis of the Hengduan Mountains have influenced the evolution of Impatiens sect. Impatiens (Balsaminaceae) in the Northern Hemisphere.

BACKGROUND: Impatiens sect. Impatiens is distributed across the Northern Hemisphere and has diversified considerably, particularly within the Hengduan Mountains (HDM) in southwest China. Yet, the infra-sectional phylogenetic relationships are not well resolved, largely due to limited taxon sampling and an insufficient number of molecular markers. The evolutionary history of its diversification is also poorly understood. In this study, plastome data and the most complete sampling to date were used to reconstruct a robust phylogenetic framework for this section. The phylogeny was then used to investigate its biogeographical history and diversification patterns, specifically with the aim of understanding the role played by the HDM and past climatic changes in its diversification. RESULTS: A stable phylogeny was reconstructed that strongly supported both the monophyly of the section and its division into seven major clades (Clades I-VII). Molecular dating and ancestral area reconstruction suggest that sect. Impatiens originated in the HDM and Southeast China around 11.76 Ma, after which different lineages dispersed to Northwest China, temperate Eurasia, and North America, mainly during the Pliocene and Pleistocene. An intercontinental dispersal event from East Asia to western North America may have occurred via the Bering Land Bridge or Aleutian Islands. The diversification rate was high during its early history, especially with the HDM, but gradually decreased over time both within and outside the HDM. Multiple linear regression analysis showed that the distribution pattern of species richness was strongly associated with elevation range, elevation, and mean annual temperature. Finally, ancestral niche analysis indicated that sect. Impatiens originated in a relatively cool, middle-elevation area. CONCLUSIONS: We inferred the evolutionary history of sect. Impatiens based on a solid phylogenetic framework. The HDM was the primary source or pump of its diversity in the Northern Hemisphere. Orogeny and climate change may have also shaped its diversification rates, as a steady decrease in the diversification rate coincided with the uplift of the HDM and climate cooling. These findings provide insights into the distribution pattern of sect. Impatiens and other plants in the Northern Hemisphere.