Search

Abstract Wind speed is one of the main control factors of wind erosion and dust emissions, which are major problems in arid and semiarid regions of the world. Accurately simulating highly precise hourly wind speeds is critical and cost-efficient for land management decisions with the goal of mitigating wind erosion and land degradation. The Wind Erosion Prediction System (WEPS) is a process-based, daily time-step model that simulates changes in the soil–vegetation–atmosphere. However, to date, relatively few studies have been conducted to test the ability of the WEPS in simulating hourly wind speeds. In this study, the performance of the WEPS model was tested in the Inland Pacific Northwest (iPNW), where wind erosion is a serious problem. Hourly wind speeds were observed and simulated by the WEPS at 13 meteorological stations from 2009 to 2018 using the WEPS hourly wind speed probability histogram. Owing to increasing wind shear, the model is not as precise in reproducing high wind speeds. The WEPS inadequately simulated the hourly wind speeds at six of the 13 stations, with a low index of agreement (d 0.5 at nine of the 13 stations. Our results suggest that the WEPS can accurately simulate hourly wind speeds and assess wind erosion in the absence of interpolation, whereas the model may be uncertain when invoking spatial interpolation. Some evidence also suggests that the model may have a tendency to underestimate observed hourly wind speeds. Pragmatically, this suggests that model users should consider the possibility that WEPS may underestimate wind erosion risk in the iPNW and plan implementation of conservation practices accordingly.

A micro-tiller vibrates severely during the rotary tillage process, which may cause operators to develop white finger disease. However, for most vibration models, the acting force between the soil and the rotary cutter roll was simplified to only a constant or sine curve, which may not describe the whole dynamic. Rotary tillage processes have been simulated based on the smoothed particle hydrodynamics method in this paper. The acting forces of the soil on the cutter roll have been obtained with the simulation model. Four different working conditions were simulated. The average error between the calculated forces and the simulated mean forces is 10.96%, which proves the SPH model. By introducing simulated acting forces into the vibration model, a new vibration model of the micro-tiller, which includes the soil–blade interaction, has been constructed. Time and frequency characteristics were simulated with the new vibration model. The errors between the simulated and tested RMS values are 4.28%, 5.03%, and 6.35% for the engine, cutter roll, and right handle, respectively. Two domain-dominant frequencies were found with the vibration model, namely 44.7 Hz and 257.0 Hz. It is helpful to reveal the whole dynamic map of micro-tillers.

Abstract The importance of fuel mixing for the progress of the scramjet engine is indisputable. The present article shows the importance of the non-equal multi-injector system for effective fuel distribution and flame holding inside the combustion segment of a scramjet engine. The supersonic air and fuel jet flow in the non-equal nozzle arrangement is simulated via computational fluid dynamic technique. Two injector types of circular and rectangular nozzle have been analyzed to attain flow characteristics of hydrogen jets at supersonic cross flow. Mach contour is also analyzed for these jet arrangements to show the interface of the jet in the non-equal jet arrangement. Besides, addition of internal air jet is also simulated and evaluated in this research. Our investigation shows that the diffusion height of the fuel jet is higher when a rectangular non-equal nozzle is applied. The circular nozzle is more active in the spreading of the fuel in the combustor and the use of an internal air jet effectively increases fuel in a combustor of the scramjet.

Abstract Kidney Clear Cell Carcinoma (KIRC), the predominant form of kidney cancer, exhibits a diverse therapeutic response to Immune Checkpoint Inhibitors (ICIs), highlighting the need for predictive models of ICI efficacy. Our study has constructed a prognostic model based on 13 types of Programmed Cell Death (PCD), which are intertwined with tumor progression and the immune microenvironment. Validated by analyses of comprehensive datasets, this model identifies seven key PCD genes that delineate two subtypes with distinct immune profiles and sensitivities to anti-PD-1 therapy. The high-PCD group demonstrates a more immune-suppressive environment, while the low-PCD group shows better responses to PD-1 treatment. In particular, TOP2A emerged as crucial, with its inhibition markedly reducing KIRC cell growth and mobility. These findings underscore the relevance of PCDs in predicting KIRC outcomes and immunotherapy response, with implications for enhancing clinical decision-making.

AbstractContext Gastrodin has been used as antihypertension therapy in China; however, the mechanisms underlying the effects of gastrodin have yet to be fully elucidated.Objective To explore the therapeutic efficiency of gastrodin as an antihypertensive and determine the mechanisms underlying this effect.Materials and methods C57BL/6 mice were continuously administered angiotensin II (Ang II) (500 ng/kg/min) to induce hypertension. Mice were randomly divided into control, Ang II and Ang II + gastrodin groups. Mice received intragastric administration of gastrodin (5 mg/kg) or double distilled water once a day for 4 weeks. Blood pressure, pulse wave velocity (PWV), thickness of the abdominal aorta, pathological morphology and differential expression transcripts (DETs) were assessed. Abdominal aorta rings and primary isolated vascular smooth muscle cells were subjected to Ang II stimulation to induce hypertension as ex vivo and in vitro models, respectively. Vascular ring tension, release of Ca2+ and levels of proteins involved in the myosin light chain kinase (MLCK)/phospho-myosin light chain 2 (p-MLC2) pathway were determined.Results Gastrodin treatment attenuated increases in blood pressure, PWV and thickness of the abdominal aorta. Treatment with gastrodin resulted in 2785 DETs and the enrichment of vascular contraction and calcium signalling pathways. Gastrodin treatment attenuated Ang II-induced vasoconstriction, produced a norepinephrine-precontracted vasodilation effect (attenuated by verapamil), and reduced intracellular Ca2+ release. Furthermore, gastrodin suppressed activation of the MLCK/p-MLC2 pathway in vivo and in vitro.Conclusions Gastrodin treatment lowers blood pressure, suppresses Ang II-induced vascular contraction and MLCK/p-MLC2 pathway activation, thereby demonstrating the mechanisms underlying the therapeutic efficacy of gastrodin as an antihypertensive.

Gastrodin, a highly potent compound found in the traditional Chinese medicine Gastrodia elata Blume, exhibits significant antihypertensive properties. However, its role and the mechanism behind its protective effects on hypertensive cardiac conditions are not well understood. This study aims to investigate the cardiac protective effects and underlying mechanisms of gastrodin in angiotensin II (Ang II)-induced hypertensive models, both in vivo and in vitro. Treatment with gastrodin significantly decreased blood pressure and the heart weight/tibial length (HW/TL) ratio and attenuated cardiac dysfunction and pathological damage in Ang II-infused C57BL/6 mice. RNA sequencing analysis (RNA-seq) revealed 697 up-regulated and 714 down-regulated transcripts, along with 1105 signaling pathways, in Ang II-infused C57BL/6 mice following gastrodin treatment, compared to Ang II-induced hypertensive mice. Furthermore, the analyses of the top 30 Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway indicated significant enrichment in apoptosis and the peroxiredoxin 2 (PRDX2)/p53 pathway. Consistently, gastrodin treatment significantly reduced myocardial apoptosis in both the cardiac tissues of Ang II-induced hypertensive mice and Ang II-stimulated H9c2 cells. Additionally, gastrodin treatment significantly decreased the protein levels of PRDX2, p53, cleaved caspase-3, cleaved caspase-9, and Bax/Bcl-2 ratio in the cardiac tissues of Ang II-infused mice and H9c2 cells stimulated with Ang II. In conclusion, gastrodin treatment can mitigate hypertension-induced myocardial apoptosis in hypertensive mice by inhibiting the PRDX2/p53 pathway.

Drug-induced liver injury is a prevalent adverse event associated with pharmaceutical agents. More significantly, there are certain drugs that present severe hepatotoxicity only during the clinical phase, consequently leading to the termination of drug development during clinical trials or the withdrawal from the market after approval. The establishment of an evaluation model that can sensitively manifest such hepatotoxicity has always been a challenging aspect in drug development. In this study, we build a liver-immune-microphysiological-system (LIMPS) to fully demonstrate the liver injury triggered by troglitazone (TGZ), a drug that was withdrawn from the market due to hepatotoxicity. Leveraging the capabilities of organ-on-chip technology allows for the dynamic modulation of cellular immune milieu, as well as the synergistic effects between drugs, hepatocytes and multiple immune cells. Through the LIMPS, we discovered that 1) TGZ can promote neutrophils to adhered hepatocytes, 2) the presence of TGZ enhances the crosstalk between macrophages and neutrophils, 3) the induction of damage in hepatocytes by TGZ at clinically relevant blood concentrations not observed in other in vitro experiments, 4) no hepatotoxicity was observed in LIMPS when exposed to rosiglitazone and pioglitazone, structurally similar analogs of TGZ, even at the higher multiples of blood drug concentration levels. As an immune-mediated liver toxicity assessment method, LIMPS is simple to operate and can be used to test multiple drug candidates to detect whether they will cause severe liver toxicity in clinical settings as early as possible.

BackgroundLipids are a key nutrient source for the growth and reproduction of Mycobacterium tuberculosis (Mtb). Urine-derived extracellular vesicles (EVs), because of its non-invasive sampling, lipid enrichment, and specific sorting character, have been recognized as a promising research target for biomarker discovery and pathogenesis elucidation in tuberculosis (TB). We aim to profile lipidome of Mtb-infected individuals, offer novel lipid signatures for the development of urine-based TB testing, and provide new insights into the lipid metabolism after Mtb infection.MethodsUrine-derived extracellular vesicles from 41 participants (including healthy, pulmonary tuberculosis, latent tuberculosis patients, and other lung disease groups) were isolated and individually detected using targeted lipidomics and proteomics technology platforms. Biomarkers were screened by multivariate and univariate statistical analysis and evaluated by SPSS software. Correlation analyses were performed on lipids and proteins using the R Hmisc package.ResultsOverall, we identified 226 lipids belonging to 14 classes. Of these, 7 potential lipid biomarkers for TB and 6 for latent TB infection (LTBI) were identified, all of which were classified into diacylglycerol (DAG), monoacylglycerol (MAG), free fatty acid (FFA), and cholesteryl ester (CE). Among them, FFA (20:1) was the most promising biomarker target in diagnosing TB/LTBI from other compared groups and also have great diagnostic performance in distinguishing TB from LTBI with AUC of 0.952. In addition, enhanced lipolysis happened as early as individuals got latent Mtb infection, and ratio of raft lipids was gradually elevated along TB progression.ConclusionThis study demonstrated individualized lipid profile of urinary EVs in patients with Mtb infection, revealed novel potential lipid biomarkers for TB/LTBI diagnosis, and explored mechanisms by which EV lipid raft-dependent bio-processes might affect pathogenesis. It lays a solid foundation for the subsequent diagnosis and therapeutic intervention of TB.

As two significant pollutants, the increased concentrations of copper ions and microplastics in coastal waters pose a substantial threat to the health of marine ecosystems. This study explored the individual and combined toxic effects of copper ions and microplastics on the marine diatom Skeletonema costatum. The results indicated that copper ions at a concentration of 0.05 mg/L exerted a negative impact on the growth of S. costatum; however, the influence of microplastics on algal cell growth was more complex: there was no significant inhibition of algal cell growth observed within the first 72 h of cultivation, but a pronounced negative effect on cell growth was noted between 72 and 96 h, with high concentrations (10.00 mg/L) of microplastics even causing a premature stagnation phase in algal cell growth. When both pollutants were present simultaneously, their impact on cell growth was similar to that of the microplastic pollution group, yet the growth condition was better than that of the copper ion pollution group. Through investigation of adsorption rates and toxicity mitigation rates, it was found that the adsorption of copper ions by microplastics was a significant reason for the improved growth condition of algal cells in the mixed pollution group compared to the copper ion pollution group. However, in the later stages of cultivation, the inhibitory effect of microspheres on algal cell growth counteracted their mitigating effect on copper ion toxicity. This study provides a reference for evaluating the impact of microplastics and heavy metals on coastal ecosystem health and for revealing the interactions between different pollutants.

Objective: This study introduces a novel methodology combining rapid stretch compound training with blood flow restriction (BFR) to investigate post activation performance enhancement (PAPE) in basketball players, a field that has been predominantly explored for lower limbs. We aimed to assess the efficacy of this combined approach on upper limb muscle performance in athletes. Methods: We employed a randomized, self-controlled crossover trial with ten male basketball players. The bench press throw (BPT) served as the primary metric, with players undergoing four interventions post-baseline: (1) STR—plyometric training; (2) BFR—blood flow restriction; (3) COMB—STR integrated with BFR; and (4) CON—control. Innovatively, we utilized an intelligent tracking sensor to precisely measure peak power (PP), peak velocity (PV), mean power (MP), and mean velocity (MV) at 4, 8, and 12 min post-intervention, providing a detailed temporal analysis of PAPE. Results: The COMB intervention demonstrated superior PAPE effects at 4 min, significantly outperforming STR and BFR alone and the control group across all measured indices (p < 0.05). Notably, the COMB group maintained these improvements for PV, PP, and H up to 12 min post-intervention, suggesting a prolonged effect. Conclusion: (1) The COMB stimulation has been shown to successfully induce PAPE more effectively than STR and BFR modality alone. (2) It appears that the optimal effects of PAPE are achieved within 4 min of exercising under this COMB. By the 12 min mark, only the COMB group continued to show significant improvements in PV, PP, and H compared to both the baseline and the CON group, while the effects in the STR and BFR groups further diminished. This suggests that although the PAPE effect is maintained over time, its optimal performance may peak at the 4 min mark and then gradually weaken as time progresses.

Abstract Background Diabetic retinopathy (DR) is a common cause of visual impairment. Apigenin has been shown to have antiangiogenic effects in various diseases. Our study aimed to investigate the role of apigenin in DR and elucidate the underlying mechanism. Methods Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG) to establish a DR model. HRMECs were treated with apigenin. Then we knocked down or overexpressed miR-140-5p and HDAC3, and added PI3K/AKT inhibitor LY294002. The expression levels of miR-140-5p, HDAC3, and PTEN were measured using qRT-PCR. Western blot analysis was performed to assess the expression of HDAC3, PTEN, and PI3K/AKT pathway-related proteins. Finally, cell proliferation and migration were evaluated using MTT, wound-healing assay, and transwell assay, while angiogenesis was examined using the tube formation assay. Results HG treatment resulted in reduced miR-140-5p expression and overexpression of miR-140-5p suppressed proliferation, migration, and angiogenesis of the HG-induced HRMECs. Apigenin treatment significantly restored the decreased level of miR-140-5p caused by HG treatment and inhibited proliferation, migration, and angiogenesis of the HG-induced HRMECs by upregulating miR-140-5p. Moreover, miR-140-5p targeted HDAC3, and overexpression of miR-140-5p reversed the HG-inducted upregulation of HDAC3 expression. HDAC3 was found to bind to the promoter region of PTEN, inhibiting its expression. Knockdown of HDAC3 suppressed the PI3K/AKT pathway by elevating PTEN expression. Furthermore, apigenin inhibited angiogenesis in DR cell models through the regulating of the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. Conclusions Apigenin effectively suppressed angiogenesis in HG-induced HRMECs by modulating the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. Our study may contribute to the development of novel therapeutic approaches and identification of potential targets for the treatment of DR.

Abstract Background Circular RNAs (circRNAs) are associated with propofol‐mediated inhibitory effect on non‐small cell lung cancer (NSCLC) progression. Circular hsa_circ_0003028 (circ_0003028) exerts a tumor‐promoting role in NSCLC. However, it is unclear whether propofol can mediate NSCLC progression via regulating circ_0003028 expression. Methods A total of 36 NSCLC patients were recruited in the study. Cell viability, proliferation, apoptosis, migration, and invasion were determined by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT), colony formation, flow cytometry, and transwell assays. Relative expression of circ_0003028 in NSCLC samples and cells was detected by quantitative real‐time polymerase chain reaction (RT‐qPCR). Analysis of the latent binding of circ_0003028 to miR‐1305 was done by bioinformatic analysis and confirmed by luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenografting in mice was done to verify the relationship between propofol and circ_0003028. Results Significant upregulation of circ_0003028 was detected in NSCLC samples and cells. Functionally, propofol treatment reduced circ_0003028 expression in NSCLC cells, and circ_0003028 overexpression impaired propofol‐mediated inhibitory effect on NSCLC cell proliferation, migration, and invasion. Interestingly, circ_0003028 could compete with miR‐1305 as a competing endogenous RNA and upregulate CORO1C expression in NSCLC cells. Conclusion Propofol‐mediated inhibiting effect on NSCLC growth partly depended on the circ_0003028/miR‐1305/CORO1C axis.

Various assessments have contributed to inconsistent findings regarding the correlation between core stability and vertical jumps. Therefore, this study aimed to re-examine this correlation based on novel core stability assessments. Twenty-one recreationally active male college students (age, 21.7 ± 2.1 years; stature, 174.9 ± 6.7 cm; body mass, 67.7 ± 7.8 kg; leg length, 88.9 ± 4.8 cm; arm length, 87.8 ± 4.0 cm) participated in this experiment. Core stability was divided into static and dynamic core stabilities, with the static core stability measured using the Eight-Level Prone Bridge and Five-Level Side Bridge tests and the dynamic core stability measured using the Y Balance Test (YBT). These tests comprehensively evaluate core stability as it is defined. Kinematic and kinetic data on vertical jumps were collected to provide process information beyond the outcome performance. Subsequently, these data were correlated with core stability for a deeper insight into the relationship between core stability and the process and outcome performance of vertical jumps. The main results revealed that the Eight-Level Prone Bridge demonstrated moderate to substantial correlations with Δ Fy‾, Δ Iy, ΔDleftkneez, and ΔDleftankley (−0.62 ≤ r ≤ 0.52); the Five-Level Side Bridge exhibited moderate correlations with Δ Fx‾, Δ Fy‾, Δ Ix, Δ Iy, ΔDleftkneez, and ΔDleftankley (−0.52 ≤ r ≤ 0.59); YBT displayed moderate correlations with Fz‾, Fleftz‾, Δ Dleftankley, Δ Drightankley, Δ Dleftanklez, Δ Drightanklez, NΔ Tankley‾, and N Tleftanklez‾ (−0.54 ≤ r ≤ 0.54) during the propulsive phase of vertical jumps. However, no significant correlations were observed between static/dynamic core stability and jumping height. Therefore, individuals with greater core stability should experience improved process performance (better movement quality), although this benefit is ineffective in translating into jumping height improvement due to impaired explosive features. Coaches may consider core stability in training to trigger an improved process performance of the vertical jump when the technique is the key issue to be solved, although future studies are required to verify this further.

Hand compartment syndrome is a rare condition due to trauma and vascular obstruction or injury, such as fluid extravasation, vascular obstruction, or arterial injury from arterial line insertion during anesthesia. However, perioperative hand compartment syndrome with no apparent preexisting cause during anesthesia that requires fasciotomy is extremely rare. We report a case on a 54-year-old male with history significant for stage IIIA moderately differentiated adenocarcinoma of the rectum who was scheduled for ultralow rectal resection and cystourethroscopy with insertion of urethral stent. Following surgery, in which he was in a safe-T-Secure positioner in a prolonged Trendelenburg position, the patient developed compartment syndrome of the right hand. This case and literature review highlights the risk for hand compartment syndrome when patients have increased Body Mass Index, positioning involves tucking of the arms, and the procedure duration is prolonged.

The physical and mechanical properties of graphene-reinforced epoxy (epoxy/graphene) in hygrothermal environment need to be comprehensively understood. This is because it is necessary to predict the durability of epoxy/graphene when epoxy/graphene is used in an aggressive environment with high humidity and high temperature. Based on the molecular dynamics method, the influences of water content (2, 4 and 6%) and temperature (298,333 and 368 K) on the physical and tensile properties of epoxy/graphene were studied in this research. The results showed that after the addition of graphene, the free volume fraction of epoxy and the diffusion coefficient of water molecules in the epoxy decreased, and the density, tensile strength and deformation performance of epoxy increased. In the hygrothermal environment, the tensile strength degradation rate of epoxy/graphene was lower than that of pure epoxy. The failure mechanism and mechanical response of epoxy/graphene during the tensile process in the nanoscale were revealed. The research results provide a reference for the design and performance optimization of epoxy/graphene composites in a hygrothermal environment.

Establishing highly effective charge transfer channels in carbon nitride (g-C3N4) to enhance its photocatalytic activity is still a challenging issue. Herein, the delaminated 2D Ti3C2 MXene nanosheets were employed to decorate the P-doped tubular g-C3N4 (PTCN) for engineering 1D/2D Schottky heterojunction (PTCN/TC) through electrostatic self-assembly. The optimized PTCN/TC exhibited the highest hydrogen evolution rate (565 μmol h−1 g−1), which was 4.3 and 2.0 -fold higher than pristine bulk g-C3N4 and PTCN, respectively. Such enhancement may be primarily attributed to the phosphorus heteroatom doped and unique structure of 1D/2D g-C3N4/Ti3C2 Schottky heterojunction, enhancing the light-harvesting and charges’ separation. One-dimensional pathway of g-C3N4 tube and built-in electric field of interfacial Schottky effect can significantly facilitate the spatial separation of photogenerated charge carriers, and simultaneously inhibit their recombination via Schottky barrier. In this composite, metallic Ti3C2 was served as electrons sink and photons collector. Moreover, ultrathin Ti3C2 flake with exposed terminal metal sites as a co-catalyst exhibited higher photocatalytic reactivity in H2 evolution compared to carbon materials (such as reduced graphene oxide). This work not only proposed the mechanism of tubular g-C3N4/Ti3C2 Schottky junction in photocatalysis, but also provided a feasible way to load ultrathin Ti3C2 as a co-catalyst for designing highly efficient photocatalysts.

In this article, quality rapid determination of cherry fruit (Prunus spp.) using artificial olfactory technique (AOT) combined with non-linear data extraction model was studied. AOT system was developed and used for cherry quality detection. AOT system responses to cherry samples stored at 4°C were recorded. At the same time, physical/chemical indexes, such as human sensory evaluation (HSE), firmness, color, pH, total soluble solids (TSS), and reducing sugar content (RSC), were examined to provide quality references to the cherry samples. AOT data was analyzed by principal component analysis (PCA), and bilayer stochastic resonance (BSR) models. PCA only partially discriminated the cherry samples. The signal-to-noise ratio (SNR) maximum values (SNR-Max) generated by BSR successfully discriminated all the samples. Multiple variable regression (MVR) between cherry physical/chemical indexes and BSR SNR-Max values was conducted. Results indicated that BSR was suitable for cherry quality rapid evaluation. Cherry quality examination model was built based on linear fitting regression on BSR eigen values. Validation tests results indicated that the developed model has good forecasting accuracy. The proposed method had some advantages, such as rapid responses, high accuracy, easy operation, etc.

IntroductionTwo-line hybrid rice based on Photoperiod/thermo-sensitive genic male sterile (P/TGMS) lines has been developed and applied widely in agriculture due to the freedom in making hybrid combinations, less difficulty in breeding sterile lines, and simpler procedures for breeding and producing hybrid seed. However, there are certain risks associated with hybrid seed production; if the temperature during the P/TGMS fertility-sensitive period is lower than the critical temperature, seed production will fail due to self-pollination. In a previous study, we found that the issue of insufficient purity of two-line hybrid rice seed could be initially addressed by using the difference in tolerance to β-triketone herbicides (bTHs) between the female parent and the hybrid seeds.MethodsIn this study, we further investigated the types of applicable herbicides, application methods, application time, and the effects on physiological and biochemical indexes and yield in rice.ResultsThe results showed that this method could be used for hybrid purification by soaking seeds and spraying plants with the bTH benzobicylon (BBC) at safe concentrations in the range of 37.5-112.5 mg/L, and the seeds could be soaked in BBC at a treatment rate of 75.0 mg/L for 36-55 h without significant negative effects. The safe concentration for spraying in the field is 50.0-400.0 mg/L BBC at the three-leaf stage. Unlike BBC, Mesotrione (MST) can only be sprayed to achieve hybrid purification at concentrations between 10.0 and 70.0 mg/L without affecting yield. The three methods of hybrid seed purification can reach 100% efficiency without compromising the nutritional growth and yield of hybrid rice. Moreover, transcriptome sequencing revealed that 299 up-regulated significant differentially expressed genes (DEGs) in the resistant material (Huazhan) poisoned by BBC, were mainly enriched in phenylalanine metabolism and phenylpropanoid biosynthesis pathway, it may eliminate the toxic effects of herbicides through this way.DiscussionOur study establishes a foundation for the application of the bTH seed purification strategy and the three methods provide an effective mechanism for improving the purity of two-line hybrid rice seeds.

ABSTRACT Colistin is one of the last-resort antibiotics for treating infections caused by multidrug-resistant (MDR) Gram-negative bacteria. However, mcr genes conferring resistance to colistin have been widely identified, which is considered a global threat to public health. Here, we investigated the prevalence and characteristics of mcr-harboring Escherichia coli strains isolated from humans, animals, and foods in China by PCR, antimicrobial susceptibility testing, conjugation experiments, molecular typing, genome sequencing, and bioinformatics analysis. In total, 135 mcr-1-harboring E. coli isolates were acquired from 847 samples, and 6 isolates carried mcr-3. Among them, 131 isolates were MDR bacteria. Sixty-five resistance genes conferring resistance to multiple antimicrobials were identified in 135 isolates. The diverse pulsed-field gel electrophoresis (PFGE) patterns and sequence types (STs) of mcr-1-carrying isolates demonstrated that clonal dissemination was not the dominant mode of mcr-1 transmission. Seven types of plasmids were able to carry mcr-1 in this study, including IncI2, IncX4, IncHI2, p0111, IncY, and two hybrid plasmids. The genetic structures carrying mcr-1 of 60 isolates were successfully transferred into the recipient, including 25 IncI2 plasmids, 23 IncX4 plasmids, and an IncHI2 plasmid. mcr-1–pap2 was the dominant mcr-1-bearing structure, followed by ISApl1–mcr-1–pap2–ISApl1 (Tn6330) and ISApl1–mcr-1–pap2, among 7 mcr-1-bearing structures of 135 isolates. In conclusion, IncI2, IncX4, and IncHI2 plasmids were the major vectors spreading mcr-1 from different geographical locations and sources. The prevalence of Tn6330 may accelerate the transmission of mcr-1. Continuous surveillance of mcr-1 and variants in bacteria is vital for evaluating the public health risk posed by mcr genes. IMPORTANCE The spread of polymyxin-resistant Enterobacteriaceae poses a significant threat to public health and challenges the therapeutic options for treating infections on a global level. In this study, mcr-1-bearing ST10 E. coli was isolated from pigs, pork, and humans simultaneously, which demonstrated that ST10 E. coli was an important vehicle for the spread of mcr-1 among animals, foods, and humans. The high prevalence of mcr-1-positive E. coli strains in pigs and pork and the horizontal transmission of mcr-1-bearing plasmids in diverse E. coli strains suggest that pigs and pork are important sources of mcr-1-positive strains in humans and pose a potential threat to public health. Additional research on the prevalence and characteristics of mcr-1-positive E. coli is still required to facilitate early warning to improve polymyxin management in hospitals.

In recent years, both domestic and international research on quadruped robots has advanced towards high dynamics and agility, with a focus on high-speed locomotion as a representative motion in high-dynamic activities. Quadruped animals like cheetahs exhibit high-speed running capabilities, attributed to the indispensable role played by their flexible spines during the flight phase motion. This paper establishes dynamic models of flexible spinal quadruped robots with different degrees of simplification, providing a parameterized description of the flight phase motion for both rigid-trunk and flexible-spine quadruped robots. By setting different initial values for the spine joint and calculating the flight phase results for both types of robots at various initial velocities, the study compares and analyzes the impact of a flexible spine on the flight phase motion of quadruped robots. Through comparative experiments, the research aims to validate the influence of a flexible spine during the flight phase motion, providing insights into how spine flexibility affects the flight phase motion of quadruped robots.

The raccoon dog (Nyctereutes procyonoides) is a typical omnivore possessing wide dietary adaptability and tolerance to rough feeding, which may be attributed to its intestinal microbiota. The study aimed to investigate the effect of dietary alfalfa meal levels on the growth performance, nutrient apparent digestibility, serum parameters, and intestinal microbiota of raccoon dogs. Sixty raccoon dogs were randomly divided into four dietary treatments containing 0% (AM0), 5% (AM5), 10% (AM10), and 15% (AM15) alfalfa meal for a 60-day experiment. The results showed that compared to raccoon dogs fed the AM0 diet, those fed the AM5 and AM10 diets had no significant difference in growth performance, while those fed the AM15 diet experienced a significant decrease. Raccoon dogs fed the AM5 diet had no significant effect on the nutrient apparent digestibility. Dietary supplementation with alfalfa meal significantly decreased serum urea levels and increased the antioxidant capacity of raccoon dogs. The intestinal microbiome analysis showed that the richness and diversity of colonic microbiota significantly increased in the AM15 group. With the increase in dietary alfalfa meal levels, the relative abundance of fiber-degrading bacteria in the colon of raccoon dogs, such as Treponema, Phascolarctobacterium, and Christensenellaceae R-7 group, increased. However, the relative abundance of pathogenic bacteria, including Anaerobiospirillum, decreased. In conclusion, the inclusion of 5% alfalfa meal in the raccoon dogs’ diet had no effect on growth performance, but it exhibited the potential to improve serum antioxidant capacity and intestinal microbiota. This indicates that raccoon dogs have a certain tolerance to the addition of alfalfa meal in their diet.

Background: The aim of this study was to investigate the effects of different pressurization modes during high-load bench press training on muscle activation and subjective fatigue in bodybuilders. Methods: Ten bodybuilders participated in a randomized, self-controlled crossover experimental design, performing bench press training under three different pressurization modes: T1 (low pressure, high resistance), T2 (high pressure, high resistance), and C (non-pressurized conventional). Surface EMG signals were recorded from the pectoralis major, deltoid, and triceps muscles using a Delsys Trigno wireless surface EMG during bench presses. Subjective fatigue was assessed immediately after the training session. Results: (1) Pectoralis major muscle: The muscle activation degree of the T1 group was significantly higher than that of the blank control group during the bench press (p < 0.05). The muscle activation degree of the T2 group was significantly higher than that of the C group during the bench press (p < 0.05). In addition, the muscle activation degree of the T2 group was significantly higher than that of the T1 group during the first group bench press (p < 0.05). (2) Deltoid muscle: The muscle activation degree of the T2 group during the third group bench press was significantly lower than the index values of the first two groups (p < 0.05). The muscle activation degree in the experimental group was significantly higher than that in the C group (p < 0.05). The degree of muscle activation in the T2 group was significantly higher than that in the T1 group during the first bench press (p < 0.05). (3) Triceps: The muscle activation degree of the T1 group was significantly higher than the index value of the third group during the second group bench press (p < 0.05), while the muscle activation degree of the T2 group was significantly lower than the index value of the first two groups during the third group bench press (p < 0.05). The degree of muscle activation in all experimental groups was significantly higher than that in group C (p < 0.05). (5) RPE index values in all groups were significantly increased (p < 0.05). The RPE value of the T1 group was significantly higher than that of the C group after bench press (p < 0.05). The RPE value of the T1 group was significantly higher than that of the C group after bench press (p < 0.05). In the third group, the RPE value of the T1 group was significantly higher than that of the C and T2 groups (p = 0.002) (p < 0.05). Conclusions: The activation of the pectoralis major, triceps brachii, and deltoid muscles is significantly increased by high-intensity bench press training with either continuous or intermittent pressurization. However, continuous pressurization results in a higher level of perceived fatigue. The training mode involving high pressure and high resistance without pressurization during sets but with 180 mmHg occlusion pressure and pressurization during rest intervals yields the most pronounced overall effect on muscle activation.

Abstract Background Tuberculosis (TB) had been the leading lethal infectious disease worldwide for a long time (2014–2019) until the COVID-19 global pandemic, and it is still one of the top 10 death causes worldwide. One important reason why there are so many TB patients and death cases in the world is because of the difficulties in precise diagnosis of TB using common detection methods, especially for some smear-negative pulmonary tuberculosis (SNPT) cases. The rapid development of metabolome and machine learning offers a great opportunity for precision diagnosis of TB. However, the metabolite biomarkers for the precision diagnosis of smear-positive and smear-negative pulmonary tuberculosis (SPPT/SNPT) remain to be uncovered. In this study, we combined metabolomics and clinical indicators with machine learning to screen out newly diagnostic biomarkers for the precise identification of SPPT and SNPT patients. Methods Untargeted plasma metabolomic profiling was performed for 27 SPPT patients, 37 SNPT patients and controls. The orthogonal partial least squares-discriminant analysis (OPLS-DA) was then conducted to screen differential metabolites among the three groups. Metabolite enriched pathways, random forest (RF), support vector machines (SVM) and multilayer perceptron neural network (MLP) were performed using Metaboanalyst 5.0, “caret” R package, “e1071” R package and “Tensorflow” Python package, respectively. Results Metabolomic analysis revealed significant enrichment of fatty acid and amino acid metabolites in the plasma of SPPT and SNPT patients, where SPPT samples showed a more serious dysfunction in fatty acid and amino acid metabolisms. Further RF analysis revealed four optimized diagnostic biomarker combinations including ten features (two lipid/lipid-like molecules and seven organic acids/derivatives, and one clinical indicator) for the identification of SPPT, SNPT patients and controls with high accuracy (83–93%), which were further verified by SVM and MLP. Among them, MLP displayed the best classification performance on simultaneously precise identification of the three groups (94.74%), suggesting the advantage of MLP over RF/SVM to some extent. Conclusions Our findings reveal plasma metabolomic characteristics of SPPT and SNPT patients, provide some novel promising diagnostic markers for precision diagnosis of various types of TB, and show the potential of machine learning in screening out biomarkers from big data.

A patient complaining of edema of the face and lower extremities was admitted to the nephrology department for nephrotic syndrome. Renal biopsy revealed findings of minimal change disease (MCD). Thyroid ultrasound showed a hypoechoic 16 × 13 mm nodule in the right lobe, suspicious of malignancy. Later, total thyroidectomy confirmed the diagnosis of papillary thyroid carcinoma (PTC). After surgery, MCD remitted rapidly and completely, strongly suggesting the diagnosis of MCD secondary to PTC. We report here the first adult case of the paraneoplastic finding of MCD secondary to PTC. Additionally, we discuss the possible role of the BRAF gene in the pathophysiology of PTC-associated MCD in this case and highlight the importance of tumor screening.

Ethanol exposure in neonatal mice induces acute neurodegeneration followed by long-lasting glial activation and GABAergic cell deficits along with behavioral abnormalities, providing a third trimester model of fetal alcohol spectrum disorders (FASD). Retinoic acid (RA), the active form of vitamin A, regulates transcription of RA-responsive genes and plays essential roles in the development of embryos and their CNS. Ethanol has been shown to disturb RA metabolism and signaling in the developing brain, which may be a cause of ethanol toxicity leading to FASD. Using an agonist and an antagonist specific to RA receptor α (RARα), we studied how RA/RARα signaling affects acute and long-lasting neurodegeneration and activation of phagocytic cells and astrocytes caused by ethanol administered to neonatal mice. We found that an RARα antagonist (BT382) administered 30 min before ethanol injection into postnatal day 7 (P7) mice partially blocked acute neurodegeneration as well as elevation of CD68-positive phagocytic cells in the same brain area. While an RARα agonist (BT75) did not affect acute neurodegeneration, BT75 given either before or after ethanol administration ameliorated long-lasting astrocyte activation and GABAergic cell deficits in certain brain regions. Our studies using Nkx2.1-Cre;Ai9 mice, in which major GABAergic neurons and their progenitors in the cortex and the hippocampus are labeled with constitutively expressed tdTomato fluorescent protein, indicate that the long-lasting GABAergic cell deficits are mainly caused by P7 ethanol-induced initial neurodegeneration. However, the partial reduction of prolonged GABAergic cell deficits and glial activation by post-ethanol BT75 treatment suggests that, in addition to the initial cell death, there may be delayed cell death or disturbed development of GABAergic cells, which is partially rescued by BT75. Since RARα agonists including BT75 have been shown to exert anti-inflammatory effects, BT75 may rescue GABAergic cell deficits by reducing glial activation/neuroinflammation.

BackgroundIn the therapeutic process of COVID-19, the majority of indicators that physicians have for assisting treatment have come from clinical tests represented by proteins, metabolites, and immune levels in patients’ blood. Therefore, this study constructs an individualized treatment model based on deep learning methods, aiming to realize timely intervention based on clinical test indicator data of COVID-19 patients and provide an important theoretical basis for optimizing medical resource allocation.MethodsThis study collected clinical data from a total of 1,799 individuals, including 560 controls for non-respiratory infectious diseases (Negative), 681 controls for other respiratory virus infections (Other), and 558 coronavirus infections (Positive) for COVID-19. We first used the Student T-test to screen for statistically significant differences (Pvalue

The physical compliance of interaction is an important requirement for safe and efficient collaboration between robots and humans, and the realization of human–robot compliance requires robot joints with variable stiffness similar to those of human joints. In this study, based on the tissue structure and driving principle of the human arm muscle ligament, a robot joint with variable stiffness is designed, consisting of an elastic belt and serial elastic actuator in parallel. The variable stiffness of the joint is realized by adjusting the tension length of the elastic belt. Surface electromyography (sEMG) signals of the human arm are used as the characterization quantity of joint stiffness to establish the pseudo-stiffness model of the elbow joint. The stiffness of the robot joints is adjusted in real-time to match the human arm stiffness based on the changes in sEMG signals of the human arm during operation. Real-time compliant interaction of human–robot collaboration is realized based on an end stiffness matching strategy. Additionally, to verify the effectiveness of the human joint stiffness matching-based compliance control strategy, a human–robot cooperative lifting experiment was designed. The bionic variable stiffness joint shows good stiffness adjustment, and the human–robot joint stiffness matching strategy based on human sEMG signals can improve the effectiveness and comfort of human–robot collaboration.

Platycladus orientalis leaves are rich in flavonoids and polysaccharides, which offer high medicinal and nutritional benefits. This study aimed to investigate the impact of P. orientalis leaf extract (PLE) on the growth performance, fur quality, serum parameters, and intestinal microbiota of raccoon dogs. Sixty healthy male black raccoon dogs, aged 85 (±5) days, were randomly assigned to four groups and fed a basal diet supplemented with 0, 0.25, 0.50, and 1.00 g/kg PLE for 125 days (designated as groups P0, P1, P2, and P3, respectively). The results revealed that the raccoon dogs in group P1 exhibited increased average daily gain and underfur length while showing a decreased feed/gain ratio compared to group P0 (p < 0.05). However, the heart index in group P2 was significantly lower than in group P0 (p < 0.05), and the kidney index and serum alanine aminotransferase activities in group P3 were higher than in groups P2 and P0 (p < 0.05), suggesting potential adverse effects at higher PLE dosages. Notably, dietary PLE supplementation led to a reduction in serum glucose concentrations (p < 0.05), which may have implications for glucose regulation. Furthermore, the study explored the impact of dietary supplementation with 0.25 g/kg PLE on the raccoon dogs’ intestinal microbiota using high-throughput sequencing. The results showed significant alterations in the microbial community structure, with a notable decrease in the abundance of Prevotella copri in response to 0.25 g/kg PLE supplementation (p < 0.05). In conclusion, supplementing raccoon dogs’ diet with 0.25 g/kg PLE can lead to improved growth performance and a positive influence on the intestinal microbiota. However, caution should be exercised regarding higher dosages, as they may have adverse effects on certain parameters. As a result, PLE holds promise as a potential feed additive for fur animal production.

Background: Neferine exhibits therapeutic effects on anti-hypertension. However, the effect of neferine on hypertensive vascular remodeling remains unexplored. Therefore, the current study was to investigate the effect of neferine on hypertensive vascular remodeling and its underlying mechanisms. Methods: Total 30 male spontaneously hypertensive rats (SHRs) were divided randomly into five groups, including SHR, Neferine-L (2.5 mg/kg/day), Neferine-M (5 mg/kg/day), Neferine-H (10 mg/kg/day), and Valsartan (10 mg/kg/day) groups (n = 6 for each group). Wistar Kyoto (WKY) rats were set as control group (n = 6). Noninvasive blood pressure system, ultrasound, hematoxylin and eosin staining, masson trichrome staining were used to detect the blood pressure, pulse wave velocity (PWV), pathological changes and collagen content in abdominal aortas of SHRs. RNA-sequencing and immunohistochemistry(IHC) analyses were used to identify and verify the differentially expressed transcripts and activation of associated signaling pathways in SHRs. Results: Various concentrations of neferine or valsartan treatment substantially reduced the elevation of blood pressure, PWV, and abdominal aortic thickening of SHRs. RNA-sequencing and KEGG analyses recognized 441 differentially expressed transcripts and several enriched pathways (including PI3K/AKT and TGF-β/Smad2/3 signaling pathways) after neferine treatment. Masson trichromatic staining and IHC analysis demonstrated that neferine treatment decreased the collagen content and down-regulated the protein expression of PCNA, collagen I & III, and fibronectin, as well as p-PI3K, p-AKT, TGF-β1 and p-Smad2/3 in abdominal aortic tissues of SHRs. Conclusion: Neferine treatment exhibits therapeutic effects on anti-hypertension and reduces vascular remodeling, as well as suppresses the abnormal activation of multiple signaling pathways, including PI3K/AKT and TGF-β1/Smad2/3 pathways.

This systematic review aimed to evaluate the reliability and validity of the two-point method in predicting 1RM compared to the direct method, as well as analyze the factors influencing its accuracy. A comprehensive search of PubMed, Web of Science, Scopus, and SPORTDiscus databases was conducted. Out of the 88 initially identified studies, 16 were selected for full review, and their outcome measures were analyzed. The findings of this review indicated that the two-point method slightly overestimated 1RM (effect size = 0.203 [95%CI: 0.132, 0.275]; P < 0.001); It showed that test-retest reliability was excellent as long as the test loads were chosen reasonably (Large difference between two test loads). However, the reliability of the two-point method needs to be further verified because only three studies have tested its reliability. Factors such as exercise selection, velocity measurement device, and selection of test loads were found to influence the accuracy of predicting 1RM using the two-point method. Additionally, the choice of velocity variable, 1RM determination method, velocity feedback, and state of fatigue were identified as potential influence factors. These results provide valuable insights for practitioners in resistance training and offer directions for future research on the two-point method.

Background: Gastrodin has been widely used clinically in China as an antihypertensive drug. However, its effect on hypertensive renal injury is yet to be elucidated. The current study aimed to investigate the effects of gastrodin on hypertensive renal injury and its underlying mechanisms by network pharmacology analysis and validation in vivo and in vitro.Methods: A total of 10 spontaneously hypertensive rats (SHRs) were randomly categorized into the following two groups: SHR and SHR + Gastrodin groups. Wistar Kyoto (WKY) rats were used as the control group (n = 5). The SHR + Gastrodin group was intragastrically administered gastrodin (3.5 mg/kg/day), and the rats in both WKY and SHR groups were intragastrically administered an equal amount of double-distilled water for 10 weeks. Hematoxylin-eosin, Masson’s trichrome, and Sirius red staining were used to detect the pathological changes and collagen content in the renal tissues. Network pharmacology analysis was performed to explore its potential targets and related pathways. In vitro, the CCK-8 assay was used to determine the cell viability. Immunohistochemistry and western-blotting analyses were employed to assess the protein expression associated with renal fibrosis and transforming growth factor-β1 (TGF-β1) pathway-related proteins in the renal tissues or in TGF-β1-stimulated rat kidney fibroblast cell lines (NRK-49F).Results: Gastrodin treatment attenuates renal injury and pathological alterations in SHRs, including glomerular sclerosis and atrophy, epithelial cell atrophy, and tubular dilation. Gastrodin also reduced the accumulation of collagen in the renal tissues of SHRs, which were confirmed by downregulation of α-SMA, collagen I, collagen III protein expression. Network pharmacology analysis identified TGFB1 and SMAD2 as two of lead candidate targets of gastrodin on against hypertensive renal injury. Consistently, gastrodin treatment downregulated the increase of the protein expression of TGF-β1, and ratios of both p-Smad2/Smad2 and p-Samd3/Smad3 in renal tissues of SHRs. In vitro, gastrodin (25–100 μM) treatment significantly reversed the upregulation of α-SMA, fibronectin, collagen I, as well as p-Smad2 and p-Smad3 protein expressions without affecting the cell viability of TGF-β1 stimulated NRK-49F cells.Conclusion: Gastrodin treatment significantly attenuates hypertensive renal injury and renal fibrosis and suppresses TGF-β1/Smad2/3 signaling in vivo and in vitro.

This work studies the distribution of warehouses and distribution centers (W&DCs) in California and analyzes their potential relationships with disadvantaged communities (DACs). Through aggregated spatial analyses and econometric modeling, the research compares the concentration of W&DCs in five metropolitan planning organizations (MPOs) in California. The analyses show that the weighted geometric centers of W&DCs have shifted slightly toward city central areas in all five MPOs in the last few years, contrasting to the logistics sprawl trends evidenced in previous research. In the Bay Area and Southern California, W&DCs are more prevalent in areas with higher pollution burden, according to the CalEnviroScreen (CS) score. In Southern California, the study analyzes disaggregate industrial real estate data of 49,697 property transactions (properties sold) between 1989 and 2018. On average, the size of the facilities transacted have decreased, especially for those closer to the urban center. These results are confirmed using parametric and non-parametric data analyses. During recent years, smaller and closer (to the urban core) facilities represent the largest share in the transactions, consistent with the trends in e-commerce and its associated distribution requirements. Moreover, the data show a disproportionate sitting of facilities in areas where DACs reside. The paper ends with a discussion of policy and planning recommendations.

BackgroundTaijiquan, as a physical and mental exercise, can improve the negative psychology of college students. However, it is still controversial, and the optimal exercise dose of taijiquan to interfere with negative psychology has not been evaluated.ObjectiveThis study is aimed at systematically evaluating the effect of taijiquan therapy on improving negative psychological symptoms of college students and its optimal intervention dose.MethodsSearch databases such as Web of Science, Embase, PubMed, CNKI, WFSD, etc. Collect high-quality relevant RCT studies. After screening, extracting, coding and counting the data, a META analysis is done through Review Manage 5.3 and Stata 15.0 software. PICOS established the eligibility criteria to select the studies as follows: (i) population - non-clinical of college students; (ii) intervention - taijiquan intervention; (iii) comparison - taijiquan intervention group and regular physical activity group; (iv) outcomes - depression, anxiety; and (v) study design - randomized controlled trial.ResultsA total of 12 articles and 1,000 samples were included. All of the participants are college students. Taijiquan therapy can significantly reduce the depression and anxiety symptoms of college students [SMD = −0.53, 95% CI (−0.82, −0.23)], [SMD = −0.49, 95% CI (−0.90, −0.09)], with statistical significance (P < 0.05). Subgroup analysis shows that: there is a precise focus on depression and anxiety symptoms. The intervention period is more than 12 weeks, and the best effect appears when people practice 3 times a week. The best single intervention time for depression symptoms is 60 min, and for anxiety symptoms 80–90 min. It is found that taijiquan combined with mindfulness intervention can significantly reduce negative psychological symptoms like depression and anxiety of college students than single taijiquan intervention. Funnel plot combined with sensitivity analysis, Begg, Egger test showed no publication bias.ConclusionTaijiquan intervention can effectively improve the negative psychological symptoms of college students, and it has great promotion value in colleges and universities.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022314071.

BackgroundCancer neoantigens are important targets of cancer immunotherapy and neoantigen vaccines are currently in development in pancreatic ductal adenocarcinoma (PDAC) and other cancer types. Immune regulatory mechanisms in pancreatic cancer may limit the efficacy of neoantigen vaccines. Targeting immune checkpoint signaling pathways in PDAC may improve the efficacy of neoantigen vaccines.MethodsWe used KPC4580P, an established model of PDAC, to test whether neoantigen vaccines can generate therapeutic efficacy against PDAC. We focused on two immunogenic neoantigens associated with genetic alterations in the CAR12 and CDK12 genes. We tested a neoantigen vaccine comprised of two 20-mer synthetic long peptides and poly IC, a Toll-like receptor (TLR) agonist. We investigated the ability of neoantigen vaccine alone, or in combination with PD-1 and TIGIT signaling blockade to impact tumor growth. We also assessed the impact of TIGIT signaling on T cell responses in human PDAC.ResultsNeoantigen vaccines induce neoantigen-specific T cell responses in tumor-bearing mice and slow KPC4580P tumor growth. However, KPC4580P tumors express high levels of PD-L1 and the TIGIT ligand, CD155. A subset of neoantigen-specific T cells in KPC4580P tumors are dysfunctional, and express high levels of TIGIT. PD-1 and TIGIT signaling blockade in vivo reverses T cell dysfunction and enhances neoantigen vaccine-induced T cell responses and tumor regression. In human translational studies, TIGIT signaling blockade in vitro enhances neoantigen-specific T cell function following vaccination.ConclusionsTaken together, preclinical and human translational studies support testing neoantigen vaccines in combination with therapies targeting the PD-1 and TIGIT signaling pathways in patients with PDAC.

Xanthohumol (XN) is the major prenylated chalcone of the female inflorescences (cone) of the hop plant ( Humulus lupulus ). It is also a constituent of beer, the major dietary source of prenylated flavonoids. It has shown strong antitumorigenic activity towards various types of cancer cells. In the present study, we show the impact on human hepatocarcinoma cell line HepG2 cell and potential adverse effects on rat primary hepatocytes. Cell growth/viability assay (MTT) demonstrated that HepG2 cells are highly sensitive to XN at a concentration range of 25-100 μM. The primary mode of tumor cell destruction was apoptosis as demonstrated by the binding of Annexin Ⅴ-FITC, we show that XN at a concentration of 25 μM induced apoptosis in HepG2. Further evidence that XN kills HepG2 by inducing apoptosis was provided by the impact of XN on the cleavage of PARP-1 and caspases-3. In contrast, XN concentrations up to 100 μM did not affect viability of primary rat hepatocytes in vitro, meanwhile, XN did not induce the apoptosis of primary rat hepatocytes in vitro . In summary, our data provide a rationale for clinical evaluation of XN for the treatment of liver cancer.

Parkinson’s disease (PD) has a characteristically unilateral pattern of symptoms at onset and in the early stages; this lateralization is considered a diagnostically important diagnosis feature. We aimed to compare the graph-theoretical properties of whole-brain networks generated by using resting-state functional MRI (rs-fMRI), diffusion tensor imaging (DTI), and the resting-state-informed structural connectome (rsSC) in patients with left-onset PD (LPD), right-onset PD (RPD), and healthy controls (HCs). We recruited 26 patients with PD (13 with LPD and 13 with RPD) as well as 13 age- and sex-matched HCs. Rs-fMRI and DTI were performed in all subjects. Graph-theoretical analysis was used to calculate the local and global efficiency of a whole-brain network generated by rs-fMRI, DTI, and rsSC. Two-sample t-tests and Pearson correlation analysis were conducted. Significantly decreased global and local efficiency were revealed specifically in LPD patients compared with HCs when the rsSC network was used; no significant intergroup difference was found by using rs-fMRI or DTI alone. For rsSC network analysis, multiple network metrics were found to be abnormal in LPD. The degree centrality of the left precuneus was significantly correlated with the Unified Parkinson’s Disease Rating Scale (UPDRS) score and disease duration (p = 0.030, r = 0.599; p = 0.037, r = 0.582). The topological properties of motor-related brain networks can differentiate LPD and RPD. Nodal metrics may serve as important structural features for PD diagnosis and monitoring of disease progression. Collectively, these findings may provide neurobiological insights into the lateralization of PD onset.

In recent years, the exopolysaccharide (EPS) produced by deep-sea bacteria has attracted the interest of various researchers. In the present study, we have explored the properties and structure of a novel exopolysaccharide (called BPS) produced by Bacillus enclensis AP-4 from deep-sea sediments. The maximum yield of BPS was 4.23 ± 0.17 g L−1 in a 2216E modified medium. 1H NMR studies of the purified BPS displayed α and β-configuration sugar residues, including mannose, glucosamine, glucose, galactose, and xylose in a molar ratio of 1.00: 0.09: 0.04: 0.09: 0.07. BPS showed a molecular weight of 23,434 Da and was abundant in hydroxyl and amino residues. In addition, BPS exhibited a rod-like structure with a rough surface and was dominated by C, N, and O elements. The exopolysaccharide demonstrated remarkable thermal stability, high degradation temperature, and excellent emulsification capacity compared to most reported exopolysaccharides. Moreover, BPS displayed better quenching activities against the four radicals, which provided favorable protection for the strain. Finally, the freezing experiment investigated the cryoprotective effect of BPS on E. coli and S. aureus. BPS effectively improved the cell survival ratio and maintained the activity of Na+/K+-ATPase, which facilitates culture preservation. To the best of our knowledge, our work is the first report suggesting that marine exopolysaccharide has dual-activity. This work presents the foundation for the analysis of the structure and properties of exopolysaccharides produced by deep-sea bacteria.

It explores the roles of self-efficacy and self-control in physical activity and Internet addiction. And it further provides a theoretical basis for the treatment and improvement of Internet addiction among college students. This study employs the whole group sampling method. The questionnaire was conducted on 855 college students from five universities in three provinces using the Physical Activity Level Scale, the General Self-Efficacy Scale, the Self-Control Scale, and the Chinese Internet Addiction Scale (IAS). The analyses yielded three main findings. (1) A large amount of physical activity was helpful in reducing the symptoms of Internet addiction and the problematic status of each dimension among college students. (2) A large or moderate amount of physical activity was helpful in enhancing college students’ self-efficacy. Besides, a large amount of physical activity was likely to enhance college students’ self-control. (3) The condition of physical activity not only directly has the negative correlation with college students’ Internet addiction but also influences college students’ Internet addiction through two indirect ways: the mediating role of self-control and the chain mediating role of self-efficacy and self-control. These conclusions provide a deeper understanding of the protective factors of Internet addiction among Chinese college students.

Navigation line extraction is critical for precision agriculture and automatic navigation. A novel method for extracting navigation lines based on machine vision is proposed herein using a straight line detected based on a high-ridge crop row. Aiming at the low-level automation of machines in field environments of a high-ridge cultivation mode for broad-leaved plants, a navigation line extraction method suitable for multiple periods and with high timeliness is designed. The method comprises four sequentially linked phases: image segmentation, feature point extraction, navigation line calculation, and dynamic segmentation horizontal strip number feedback. The a* component of the CIE-Lab colour space is extracted to preliminarily extract the crop row features. The OTSU algorithm is combined with morphological processing to completely separate the crop rows and backgrounds. The crop row feature points are extracted using an improved isometric segmented vertical projection method. While calculating the navigation lines, an adaptive clustering method is used to cluster the adjacent feature points. A dynamic segmentation point clustering method is used to determine the final clustering feature point sets, and the feature point sets are optimised using lateral distance and point line distance methods. In the optimisation process, a linear regression method based on the Huber loss function is used to fit the optimised feature point set to obtain the crop row centreline, and the navigation line is calculated according to the two crop lines. Finally, before entering the next frame processing process, a feedback mechanism to calculate a number of horizontal strips for the next frame is introduced to improve the ability of the algorithm to adapt to multiple periods. The experimental results show that the proposed method can meet the efficiency requirements for visual navigation. The average time for the image processing of four samples is 38.53 ms. Compared with the least squares method, the proposed method can adapt to a longer growth period of crops.

Cystine-enriched food supplements are increasingly popular due to their beneficial health effects. However, the lack of industry standards and market regulations resulted in quality issues with cystine food products, including cases of food adulteration and fraud. This study established a reliable and practical method for determining cystine in food supplements and additives using quantitative NMR (qNMR). With the optimized testing solvent, acquisition time, and relaxation delay, the method exhibited higher sensitivity, precision, and reproducibility than the conventional titrimetric method. Additionally, it was more straightforward and more economical than HPLC and LC-MS. Furthermore, the current qNMR method was applied to investigate different food supplements and additives regarding cystine quantity. As a result, four of eight food supplement samples were found to be inaccurately labeled or even with fake labeling, with the relative actual amount of cystine ranging from 0.3% to 107.2%. In comparison, all three food additive samples exhibited satisfactory quality (the relative actual amount of cystine: 97.0–99.9%). Notably, there was no obvious correlation between the quantifiable properties (price and labeled cystine amount) of the tested food supplement samples and their relative actual amount of cystine. The newly developed qNMR-based approach and the subsequent findings might help standardization and regulation of the cystine supplement market.

Abstract Background Preclinical studies and early clinical trials have shown that targeting cancer neoantigens is a promising approach towards the development of personalized cancer immunotherapies. DNA vaccines can be rapidly and efficiently manufactured and can integrate multiple neoantigens simultaneously. We therefore sought to optimize the design of polyepitope DNA vaccines and test optimized polyepitope neoantigen DNA vaccines in preclinical models and in clinical translation. Methods We developed and optimized a DNA vaccine platform to target multiple neoantigens. The polyepitope DNA vaccine platform was first optimized using model antigens in vitro and in vivo. We then identified neoantigens in preclinical breast cancer models through genome sequencing and in silico neoantigen prediction pipelines. Optimized polyepitope neoantigen DNA vaccines specific for the murine breast tumor E0771 and 4T1 were designed and their immunogenicity was tested in vivo. We also tested an optimized polyepitope neoantigen DNA vaccine in a patient with metastatic pancreatic neuroendocrine tumor. Results Our data support an optimized polyepitope neoantigen DNA vaccine design encoding long (≥20-mer) epitopes with a mutant form of ubiquitin (Ubmut) fused to the N-terminus for antigen processing and presentation. Optimized polyepitope neoantigen DNA vaccines were immunogenic and generated robust neoantigen-specific immune responses in mice. The magnitude of immune responses generated by optimized polyepitope neoantigen DNA vaccines was similar to that of synthetic long peptide vaccines specific for the same neoantigens. When combined with immune checkpoint blockade therapy, optimized polyepitope neoantigen DNA vaccines were capable of inducing antitumor immunity in preclinical models. Immune monitoring data suggest that optimized polyepitope neoantigen DNA vaccines are capable of inducing neoantigen-specific T cell responses in a patient with metastatic pancreatic neuroendocrine tumor. Conclusions We have developed and optimized a novel polyepitope neoantigen DNA vaccine platform that can target multiple neoantigens and induce antitumor immune responses in preclinical models and neoantigen-specific responses in clinical translation.

Abstract Triple-negative breast cancer (TNBC) is a high-risk subtype of breast cancer with high capacity for metastasis and lacking of therapeutic targets. Our previous studies indicated that cystathionine γ-lyase (CSE) may be a new target related to the recurrence or metastasis of TNBC. Downregulation of CSE could inhibit the growth and metastasis of TNBC. The purpose of this study was to investigate the activity of the novel CSE inhibitor I194496 against TNBC in vivo and in vitro. The anticancer activity of I194496 in vitro were detected by MTS, EdU, and transwell assays. Methylene blue assay was used to determine the H2S level. Western blot was performed to analyze the expression of related pathway proteins. Xenograft tumors in nude mice were used to analyze the anticancer activity of I194496 in vivo. I194496 exerted potent inhibitory effects than l-propargylglycine (PAG, an existing CSE inhibitor) on human TNBC cells and possessed lower toxicity in normal breast epithelial Hs578Bst cells. I194496 reduced the activity and expression of CSE protein and the release of H2S in human TNBC cells. Meanwhile, the protein levels of PI3K, Akt, phospho (p)-Akt, Ras, Raf, p-ERK, p-Anxa2, STAT3, p-STAT3, VEGF, FAK, and Paxillin were decreased in human TNBC cells administrated with I194496. Furthermore, I194496 showed more stronger inhibitory effects on human TNBC xenograft tumors in nude mice. I194496 could inhibit the growth of human TNBC cells via the dual targeting PI3K/Akt and Ras/Raf/ERK pathway and suppress the metastasis of human TNBC cells via down-regulating Anxa2/STAT3 and VEGF/FAK/Paxillin signaling pathways. CSE inhibitor I194496 might become a novel and potential agent in the treatment of TNBC.

This paper proposes a fluid-structure interaction (FSI) numerical calculation method for investigation of the elastohydrodynamic lubrication performance of the rubber-plastic double-layer water-lubricated journal bearings. The accuracy and rapidity of the FSI method are improved by studying the effect of mesh density and by comparing the calculation results with those in the literature. Based on the proposed method, a series of numerical simulations are carried out to reveal the influence of operating conditions and structural parameters on the lubrication performance of the rubber-plastic bearings. Numerical results show that the bush deformation of the rubber-plastic bearing is between that of the rubber bearing and the plastic bearing, and the deformation area is close to that of the rubber bearing. The bearing load carrying capacity increases significantly with the rotational speed, eccentricity ratio, bearing length, and decrease with the clearance. But the influences of the plastic layer elastic modulus and thickness on bearing load are unremarkable. The effect of bush deformation on bearing load is noticeable when the eccentricity ratio is more than 0.8. The results are expected to provide design references for the bearings.

Studies have shown that the circulating tumor cell (CTC) is a necessary condition for the invasion and distant metastasis of renal cell carcimona (RCC). However, few CTCs-related gene mutations have been developed which could promote the metastasis and implantation of RCC. The objective of this study is to explore the potential driver gene mutations that promote RCC metastasis and implantation based on CTCs culture. Fifteen patients with primary mRCC and three healthy subjects were included, and peripheral blood was obtained. After the preparation of synthetic biological scaffolds, peripheral blood CTCs were cultured. Successful cultured CTCs were applied to construct CTCs-derived xenograft (CDX) models, followed by DNA extraction, whole exome sequencing (WES) and bioinformatics analysis. Synthetic biological scaffolds were constructed based on previously applied techniques, and peripheral blood CTCs culture was successfully performed. We then constructed CDX models and performed WES, and explored the potential driver gene mutations that may promote RCC metastasis and implantation. Bioinformatics analysis showed that KAZN and POU6F2 may be closely related to the prognosis of RCC. We successfully performed the culture of peripheral blood CTCs and, on this basis we initially explored the potential driver mutations for the metastasis and implantation of RCC.

The texture of fresh jujube fruit is related to its popularity and commercial value. The metabolic networks and essential genes that regulate the texture of jujube (Ziziphus jujuba) fruit are still unknown. In this study, two jujube cultivars with significantly different textures were selected by a texture analyzer. The four developmental stages of the exocarp and mesocarp of jujube fruit were studied separately using metabolomic and transcriptomic analyses. Differentially accumulated metabolites were enriched in several critical pathways related to cell wall substance synthesis and metabolism. Transcriptome analysis confirmed this by finding enriched differential expression genes in these pathways. Combined analysis showed that ‘Galactose metabolism’ was the most overlapping pathway in two omics. Genes such as β-Gal, MYB and DOF may affect fruit texture by regulating cell wall substances. Overall, this study provides an essential reference for the establishment of texture-related metabolic and gene networks of jujube fruit.

The rational design of morphology and structure for oxygen reduction reaction (ORR) catalysts still remains a critical challenge. Herein, we successfully construct defect-rich and hierarchically porous Fe-N-C nanosheets (Fe-N-CNSs), by taking advantage of metal-organic complexation and a mesoporous template. Benefiting from the advantages of high density of active sites, fast mass transfer channels, and sufficient reaction area, the optimal Fe-N-CNSs demonstrate satisfactory ORR activity with an excellent half-wave potential of up to 0.87 V, desirable durability, and robust methanol tolerance. Noteworthy, the Fe-N-CNSs based zinc–air battery shows significant performance with a peak power density of 128.20 mW cm−2 and open circuit voltage of 1.53 V, which reveals that the Fe-N-CNSs catalysts present promising practical application prospects. Therefore, we believe that this research will provide guidance for the optimization of Fe-N-C materials.

For the stability analysis of rock slope, it is very critical to obtain the spatial geometric characteristics of the structural surfaces of the rock mass accurately and effectively. As for a high-steep rock slope of an iron ore mine, in order to solve the problems of inefficiency and high risk of traditional manual geological survey, the geological survey and stability evaluation of the slope was carried out by adopting unmanned aerial vehicle digital photogrammetry (UAV-DP) technology. Firstly, a large number of high-resolution images of the slope were obtained by UAV-DP. Then, the structure from motion (SFM) method was used to construct the fine 3D point cloud model of the slope, which was subjected to coplanarity detection and K-means clustering for identifying the structural surfaces. Finally, the stability and failure model of the slope cut by the structural surfaces are analyzed by using the stereo-projection and discrete element methods. The research results show that the error between UAV-DP and manual measurement is within the acceptable range, which demonstrates the reliability of UAV-DP used in the geological investigation. Furthermore, the stability state and failure model of the slope is also consistent well with the field observation.