Search

Abstract Background The use of gastrointestinal disease multiplex polymerase chain reaction (GI PCR) testing has become common for suspected gastrointestinal infection. Patients often test positive for multiple pathogens simultaneously through GI PCR, although the clinical significance of this is uncertain. Methods This retrospective cohort study investigated risk factors and clinical outcomes associated with detection of multiple (as opposed to single) pathogens on GI PCR. We included adult patients who underwent GI PCR testing from 2020 to 2023 and had one or more pathogens detected. We compared patients with multiple versus those with single pathogens and hypothesized that immunosuppression would be a risk factor for detection of multiple pathogens. We further hypothesized that, during the 90 days after GI PCR testing, patients with multiple pathogens would have worse clinical outcomes such as increased rates of emergency department (ED) visits, death, hospitalization, or ambulatory care visits. Results GI PCR was positive in 1341 (29%) of tested patients; 356 patients had multiple pathogens and 985 had one pathogen. The most common pathogens included Enteropathogenic Escherichia coli (EPEC, 27%), norovirus (17%), and Enteroaggregative E. coli (EAEC, 14%) in both multi- and singly positive patients. Immunosuppression was not associated with multiple pathogens (adjusted odds ratio [aOR] 1.35, 95% CI 0.96, 1.86). The factors most associated with multiple pathogens were Hispanic ethnicity (OR 1.86, 95% CI 1.42, 2.45) and chronic kidney disease (OR 1.69, 95% CI 1.13, 2.49). Patients with multiple pathogens were more likely to have ED visits during the 90 days after GI PCR testing (40% vs. 32%, p

Under the influence of multiple mining influences, the mining pressure is more intense and the surrounding rock deformation is large, which is easy to cause the surrounding rock instability of gob-side entry retaining in fully mechanized mining face. In order to study the surrounding rock control problem of gob-side entry retaining in large mining height working face, taking 1313 working face retaining roadway as the research background, the movement characteristics of surrounding rock of gob-side entry retaining roadway were analyzed through theoretical analysis, numerical simulation, on-site practice, and other methods. The “support unloading balance” coordinated control technology for roadway surrounding rock was proposed, which strengthened the support strength of roadway surrounding rock and improved the stress environment of roadway surrounding rock. It was verified through on-site engineering practice. The deformation of the top and bottom of the roadway in a mine 1313 working face is 246 mm, and the deformation of the two sides is 442 mm. There is no obvious bulging phenomenon on the surface of the roadway, and the deformation of the surrounding rock of the roadway meets the relevant regulations of the operation regulations.

AbstractLung cancer is a dangerous disease that is lacking in an ideal therapy. Here, we evaluated the anti-lung cancer effect in nude mice of a fully human single-chain antibody (scFv) against the associated antigen 7 transmembrane receptor (Ts7TMR), which is also called G protein-coupled receptor, between A549 cells and Trichinella spiralis (T. spiralis). Our data showed that anti-Ts7TMR scFv could inhibit lung cancer growth in a dose-dependent manner, with a tumour inhibition rate of 59.1%. HE staining did not reveal any obvious tissue damage. Mechanistically, immunohistochemical staining revealed that the scFv down-regulated the expression of PCNA and VEGF in tumour tissues. Overall, this study found that anti-Ts7TMR scFv could inhibit A549 lung cancer growth by suppressing cell proliferation and angiogenesis, which may provide a new strategy for treating lung cancer.

The refinement of bainitic ferrite laths is one of the most critical ways to improve the combination of strength and ductility. However, low-temperature bainitic transformations in the microstructural evolution of carbide-free bainite in high-carbon steels cause challenges for both the manufacture of coils and their application in car bodies. In this study, deformation-induced bainite refinement was proposed for refining bainite and retained austenite laths using a combination of ausforming and austempering in low-carbon low-alloy steel. The deformed austenite supplied more nucleation sites for bainitic transformation and suppressed the thickening of the bainitic ferrite laths by strengthening the surrounding untransformed austenite. A tensile strength of 1283 MPa and total elongation of 23.6% were obtained in the steel with an ausforming strain of 40% before austempering. The significant increase in strength was mainly attributed to the refinement of the bainitic ferrite laths and the high accumulation of dislocations within both the bainitic ferrite and retained austenite. The more stable retained austenite improved the sustainable work-hardening capability via the continuous transformation-induced plasticity effect.

Abstract Hindlimb ischaemia–reperfusion (IR) is among the most prominent pathophysiological conditions observed in peripheral artery disease (PAD). An exaggerated arterial blood pressure (BP) response during exercise is associated with an elevated risk of cardiovascular events in individuals with PAD. However, the precise mechanisms leading to this exaggerated BP response are poorly elucidated. The P2X3 signalling pathway, which plays a key role in modifying the exercise pressor reflex (EPR), is the focus of the present study. We determined the regulatory role of P2X3 on the EPR in a rat model of hindlimb IR. In vivo and in vitro approaches were used to determine the expression and functions of P2X3 in muscle afferent nerves and EPR in IR rats. We found that in IR rats there was (1) upregulation of P2X3 protein expression in the L4–6 dorsal root ganglia (DRG); (2) amplified P2X currents in isolated isolectin B4 (IB4)‐positive muscle DRG neurons; and (3) amplification of the P2X‐mediated BP response. We further verified that both A‐317491 and siRNA knockdown of P2X3 significantly decreased the activity of P2X currents in isolated muscle DRG neurons. Moreover, inhibition of muscle afferents’ P2X3 receptor using A‐317491 was observed to alleviate the exaggerated BP response induced by static muscle contraction and P2X‐induced BP response by α,β‐methylene ATP injection. P2X3 signalling pathway activity is amplified in muscle afferent DRG neurons in regulating the EPR following hindlimb IR.

Abstract Background Ankle-foot orthoses (AFO) can improve gait posture and walking ability in post-stroke patients. However, the effect of AFO on gait parameters in post-stroke patients according to the Brunnstrom stage of stroke recovery of the lower limbs remains unclear. The study aimed to investigate whether stroke patients with different Brunnstrom stages benefit from wearing AFO. Methods Twenty-five post-stroke participants included 18 men (50 ± 13 years) and 7 women (60 ± 15 years). The patients were divided based on Brunnstrom stage III or IV of the lower limbs. All patients underwent the gait and timed up and go (TUG) test using a gait analysis system while walking barefoot or with an AFO. The spatiotemporal and asymmetric parameters were analyzed. Results All 25 patients completed the study. Significant differences were observed between barefoot and AFO use in TUG time (P 0.05). The main effect of the swing time ratio was significant in both groups (P 0.05). For barefoot versus AFO, the main effects of stride length (P 0.05). Conclusions Post-stroke patients with lower Brunnstrom stages benefitted more from AFO, particularly in gait asymmetry.

Abstract Sepsis is recognized as a major contributor to the global disease burden, but there is a lack of specific and effective therapeutic agents. Utilizing Mendelian randomization (MR) methods alongside evidence of causal genetics presents a chance to discover novel targets for therapeutic intervention. MR approach was employed to investigate potential drug targets for sepsis. Pooled statistics from IEU-B-4980 comprising 11,643 cases and 474,841 controls were initially utilized, and the findings were subsequently replicated in the IEU-B-69 (10,154 cases and 454,764 controls). Causal associations were then validated through colocalization. Furthermore, a range of sensitivity analyses, including MR-Egger intercept tests and Cochran's Q tests, were conducted to evaluate the outcomes of the MR analyses. Three drug targets (PSMA4, IFNAR2, and LY9) exhibited noteworthy MR outcomes in two separate datasets. Notably, PSMA4 demonstrated not only an elevated susceptibility to sepsis (OR 1.32, 95% CI 1.20–1.45, p = 1.66E−08) but also exhibited a robust colocalization with sepsis (PPH4 = 0.74). According to the present MR analysis, PSMA4 emerges as a highly encouraging pharmaceutical target for addressing sepsis. Suppression of PSMA4 could potentially decrease the likelihood of sepsis.

Human respiratory syncytial virus (hRSV) not only affects newborns but also older adults, contributing to a substantial worldwide burden of disease. However, only three approved hRSV vaccines remain commercially available to date. The development of a safe, practical and broad-spectrum vaccine suitable for all age groups remains extremely challenging. Using five different approaches—live-attenuated, recombinant-vector, subunit, particle-based, and mRNA—nearly 30 hRSV vaccine candidates are currently conducting clinical trials worldwide; moreover, > 30 vaccines are under preclinical evaluation. This review presents a comprehensive overview of these hRSV vaccines along with prospects for the development of infectious disease vaccines in the post-COVID-19 pandemic era.

The rationality of structure parameters of the blade-type screw steel pipe pile is the major factor in determining the safety, applicability, and economy of a pile foundation, but the existing design methods have not defined the specific approaches to calculating structure parameters of blades and steel pipes. To address this issue, an analysis of the strength theory was performed on spatial helical blades, revealing the ratio of blade width to steel pipe radius as the core index to do the structure parameters design of blade-type screw steel pipe pile and established a mathematical calculation model between the vertical bearing capacity of single pile and a. The rational value of a is 2.0–3.0 using numerical calculation. The correlation between blade thickness and wall thickness of steel pipes was determined using the force analysis based on the synergy between blades and steel pipes. Then the structure parameters design method of blade-type screw steel pipe pile with coordinated parameters was proposed. The rationality and superiority of this design method were verified by comparing the existing test data and the finite element simulative analysis. Based on this design method and the current specifications, such as the Technical Code for Building Pile Foundations, a safe, applicable, and economical optimization design method and flow of blade-type screw steel pipe piles were further proposed for engineering design reference.

Shale reservoirs generally contain water that has a significant impact on shale gas adsorption behavior and geological reserve evaluation. In order to explore the influence of water content on gas adsorption behavior in shale, an adsorption model considering the influence of water content was established, the rationality of the new model was verified by combining several sets of experimental data, and gas adsorption behavior in water-bearing shale was further analyzed. On this basis, the contribution of different adsorption mechanisms to the isothermal adsorption of methane in shale was discussed, and the thermodynamic characteristics of adsorption in dry and wet shale were compared by thermodynamic parameters. The results shown that, the methane adsorption amount shown a typical “three-stage” change in the process of gas pressure change. Among them, water has an inhibitory effect on methane adsorption capacity, gas adsorption capacity in water-bearing shale was significantly lower than that in dry shale, and gas adsorption capacity decreased with the increasing water content. In addition, temperature also inhibited methane adsorption, and gas adsorption capacity in shale decreased with the increasing temperature when the water content was constant. At the same time, the contribution of different adsorption mechanisms to adsorption capacity was affected by the combination of water and pressure. The higher the pressure and water content, the lower the contribution of microporous filled adsorption to the total adsorption capacity. Thermodynamic parameters indicated that methane adsorption in both dry and water-bearing shale was physical adsorption, and the isosteric adsorption heat in dry shale was always higher than that in water-bearing shale under the same adsorption capacity. Water occupied high-energy adsorption sites and affected intermolecular forces by altering shale heterogeneity, which combined to reduce isosteric adsorption heat and hence gas adsorption capacity in water-bearing shale. The research results contributed to the accurate calculation of gas adsorption capacity in shale, and provided a theoretical basis for the development programme and compilation of shale gas reservoirs.

ObjectiveIn order to realize formation control for multiple unmanned surface vehicles (USVs) subject to practical needs, a distributed event-triggered formation control method for multiple USVs is proposed which is capable of ensuring collision avoidance and connectivity preservation. MethodsConsidering the disturbances caused by marine environments and the uncertainties of system models, a disturbance observer is designed. Aiming to avoid potential collisions and the loss of connectivity among USVs during the process of realizing the desired formations, artificial potential field functions are utilized to design a controller with collision avoidance and connectivity preservation abilities. To reduce the frequency of control updates, a distributed event-triggering mechanism is designed for each USV, enabling it to determine the execution time of its own control input based on local information. ResultsTheoretical analysis proves the uniform ultimate boundedness of formation errors, and the event-triggered mechanism does not display Zeno behaviors. The simulation results validate that the proposed control method can significantly reduce the number of controller updates and prevent collisions among USVs while maintaining their connectivity.ConclusionThe results of this study can help to ensure the safe formation control of USVs and reduce the wear and tear of control devices.

Abstract Background Assessing the efficacy and safety of Vacuum Sealing Drainage (VSD) in treating deep incision infections (DII) following posterior cervical internal fixation. Methods We retrospectively studied the clinical effects of VSD and Traditional Negative Pressure Drainage (TND) on 12 patients with deep incision infection after posterior cervical fixation surgery who were treated in our department from 2012 to 2020. A comparison of patient-related factors (age, gender, BMI, comorbidities, initial internal fixation surgery segment, preoperative laboratory inflammation indicators) and surgical-related factors (postoperative duration of fever, positive rate of drainage fluid bacterial culture, Visual Analogue Scale (VAS) score at 3 days after surgery, laboratory indicators at 3 days after surgery, debridement frequency and drainage time, hospital stay, internal fixation retention rate, and infection recurrence rate) between the VSD group and the TND group was conducted using independent sample t tests to draw experimental conclusions. Results This study included 12 patients, with six cases of VSD (5 males and 1 female) and six cases of TND (4 males and 2 females). The VSD group had significantly lower postoperative fever time (1.50 ± 0.46 days vs. 4.28 ± 0.97 days, P

[Objective] In water-rich rock stratum regions, preventing confined aquifer inrush accidents is a key focus and challenge in the design and construction of deep foundation pit projects. Accurately and effectively determining the critical thickness of foundation pit bottom plate is crucial in preventing confined aquifer inrush accidents. Therefore, it is necessary to conduct stability study on foundation pit bottom plate inrush damage problem in confined aquifer. [Method] Based on the nonlinear Mohr-Coulomb failure criterion and considering the influence of various strength parameters and the heterogeneity characteristics of soil layers, a mechanical analysis model for foundation pit bottom plate inrush damage is established. Using the limit equilibrium method, a safety factor calculation formula for bottom plate inrush stability considering the inherent strength of soil layers is proposed. The calculation method for inrush damage in the current technical specifications for foundation pit support is modified. Taking the foundation pit of a utility tunnel project in soft soil layers in Jinan as example, the effectiveness of the proposed modified calculation formula for pit bottom plate inrush stability is validated. Additionally, variations in the safety factor of bottom plate inrush stability under the influence of different soil strength parameters, impermeable layer thickness, and confined water pressure are analyzed. [Result & Conclusion] With the increase in soil cohesion, heterogeneity constant, density, and impermeable layer thickness, the safety factor of pit bottom plate inrush stability continuously increases. Conversely, as the soil nonlinear coefficient, confined water pressure, and foundation pit width increase, the safety factor of pit bottom plate inrush stability continuously decreases. The calculated values of the inrush safety factors considering the influence of soil inherent strength parameters, are generally greater than the values obtained using the current calculation method in the technical specifications for foundation support. The verification using the proposed modified inrush stability calculation formula is more economical.

Ultraviolet (UV) networks, owing to their advantages of low eavesdropping rates, low background noise, strong anti-interference abilities, and non–line-of-sight (NLOS) communication, have high prospects for application in the complex electromagnetic environment. In this study, UV network coverage was systematically evaluated based on the NLOS channel. Combined with a designed node model and a specific communication mode, a two-dimensional network coverage model was established and expressions of network coverage area and connectivity were derived mathematically. Subsequently, the effects of the transceiver elevation combination, number of nodes, data rate, and transmission power on the network coverage performance were analyzed, and the communication parameters were optimized to match different network scenarios. The results show that the bigger the transceiver elevation combination, the more stringent the communication parameters required by the UV network coverage. Finally, a coverage evaluation experiment with four-node network was conducted. This study provides theoretical reference information for actual network deployment.

SARS-CoV-2 has been evolving into a large number of variants, including the highly pathogenic Delta variant, and the currently prevalent Omicron subvariants with extensive evasion capability, which raises an urgent need to develop new broad-spectrum neutralizing antibodies. Herein, we engineer two IgG-(scFv)2 form bispecific antibodies with overlapping epitopes (bsAb1) or non-overlapping epitopes (bsAb2). Both bsAbs are significantly superior to the parental monoclonal antibodies in terms of their antigen-binding and virus-neutralizing activities against all tested circulating SARS-CoV-2 variants including currently dominant JN.1. The bsAb1 can efficiently neutralize all variants insensitive to parental monoclonal antibodies or the cocktail with IC50 lower than 20 ng/mL, even slightly better than bsAb2. Furthermore, the cryo-EM structures of bsAb1 in complex with the Omicron spike protein revealed that bsAb1 with overlapping epitopes effectively locked the S protein, which accounts for its conserved neutralization against Omicron variants. The bispecific antibody strategy engineered from overlapping epitopes provides a novel solution for dealing with viral immune evasion.

ABSTRACTType I interferons (IFN-Is) have key roles in immune defense and treatments for various diseases, including chronic hepatitis B virus (HBV) infection. All IFN-Is signal through a shared IFN-I heterodimeric receptor complex comprising IFN-α receptor 1 (IFNAR1) and IFNAR2 subunits, but differences in antiviral and immunomodulatory responses among IFN-I subtypes remain largely unknown. Because the IFN-IFNAR interactions are species-specific, mice exhibit weak responses to human IFN-I. To more fully characterize the actions of human IFN-α and its subtypes in vivo, a gene targeting strategy was employed to generate gene knock-in mice with extracellular-humanized IFNAR1/2 (IFNAR-hEC) in the C57BL/6N strain. IFNAR-hEC mice actively responded to human IFN-I, and endogenous mouse IFN-I signalling remained active in heterozygous mice (IfnarhEC/+). Analyses of IFNAR-hEC mice and isolated cells showed that human IFN-α2 and α14 subtypes exerted differential effect on the activation of JAK-STAT signalling and immune responses. Compared with IFN-α2, IFN-α14 induced greater activation of STAT1/2 and IFN-stimulated genes, synergistically elicited IFN-α and -γ signalling, and induced higher numbers of antigen-specific CD8+ T cells. Moreover, IFNAR-hEC mice with HBV replication displayed long-term viral suppression upon treatment with the clinically-used PEGylated hIFN-α2. These results indicate that IFNAR-hEC mice may be useful for elucidating antiviral and immunomodulatory functions of human IFN-Is and for conducting preclinical studies. A better understanding of the distinct activities of IFN-α subtypes can provide insights concerning the development of improved IFN-based therapy.

Background: To observe the activation strategies of the ankle muscles using surface electromyography (sEMG) during single-leg standing (SLS) and both-leg standing (BLS) on flat ground (FG), soft mat (SM), and BOSU ball (BB) surfaces. Methods: Thirty healthy young adults participated in the study. The muscle activities of the tibialis anterior (TA) and gastrocnemius medial (GM) were measured on the three surfaces during SLS and BLS. Electromyographic evaluations of the TA and GM were recorded during maximum voluntary isometric contractions (MVIC). Muscle activation was evaluated using MVIC%, and muscle co-contraction was evaluated using the co-contraction index (CI). Results: A statistically significant increase was observed in the MVIC% of the TA, GM, and CI on the three surfaces during SLS compared to BLS, except for the comparison of CI on BB between SLS and BLS (t = −1.35, p = 0.19). The MVIC% of the TA and GM during SLS and BLS on BB was significantly increased in comparison with FG and SM. The CI during BLS on BB increased compared to FG (t = 3.19, p < 0.01) and SM (t = 4.64, p < 0.01). The CI during BLS on SM (t = −1.46, p = 0.15) decreased when compared to FG but without statistical significance. Conclusions: SLS and unstable surfaces can induce greater muscle activation, and SLS can have a greater influence on ankle muscles.

Abstract In the quest for optimizing biodegradable implants, the exploration of piezoelectric materials stands at the forefront of biomedical engineering research. Traditional piezoelectric materials often suffer from limitations in biocompatibility and biodegradability, significantly impeding their in vivo study and further biomedical application. By leveraging molecular engineering and structural design, a recent innovative approach transcends the conventional piezoelectric limits of the molecules designed for biodegradable implants. The biodegradable molecular piezoelectric implants may open new avenues for their applications in bioenergy harvesting/sensing, implanted electronics, transient medical devices and tissue regeneration.

Abstract Tertiary lymphoid structure (TLS) can predict the prognosis and sensitivity of tumors to immune checkpoint inhibitors (ICIs) therapy, whether it can be noninvasively predicted by radiomics in hepatocellular carcinoma with liver transplantation (HCC‐LT) has not been explored. In this study, it is found that intra‐tumoral TLS abundance is significantly correlated with recurrence‐free survival (RFS) and overall survival (OS). Tumor tissues with TLS are characterized by inflammatory signatures and high infiltration of antitumor immune cells, while those without TLS exhibit uncontrolled cell cycle progression and activated mTOR signaling by bulk and single‐cell RNA‐seq analyses. The regulators involved in mTOR signaling (RHEB and LAMTOR4) and S‐phase (RFC2, PSMC2, and ORC5) are highly expressed in HCC with low TLS. In addition, the largest cohort of HCC patients is studied with available radiomics data, and a classifier is built to detect the presence of TLS in a non‐invasive manner. The classifier demonstrates remarkable performance in predicting intra‐tumoral TLS abundance in both training and test sets, achieving areas under receiver operating characteristic curve (AUCs) of 92.9% and 90.2% respectively. In summary, the absence of intra‐tumoral TLS abundance is associated with mTOR signaling activation and uncontrolled cell cycle progression in tumor cells, indicating unfavorable prognosis in HCC‐LT.

(1) Studying the dynamic correlation between land use and the eco-environment in the Dianchi Basin is important for improving the basin's spatial layout and enhancing ecological development and conservation; (2) Through dynamic analysis and comprehensive evaluation of land use, the introduction of ecological and environmental quality index, and the use of FLUS models, the impacts on eco-environments in the Dianchi Basin for the recent 20 years were analyzed; (3) The past two decades witnessed a constant increase in the construction land in the Dianchi Basin and a decline in the farmland at an average annual rate of 0.93 %; The utilization level of land in the Dianchi Basin presented a negative correlation with the quality of the area's eco-environment, which reduces first and then increases; When natural production becomes a priority, both the construction land and farmland have witnessed growth. However, when ecological protection becomes a priority, it is projected that by 2035, the Dianchi Basin will achieve its highest eco-environmental quality index; (4) Studying how the change of land use types affects eco-environment is crucial for optimizing the current allocation of land resources and promoting sustainable development in the basin.

As a waterless fracturing fluids for gas shale stimulation with low viscosity and strong diffusibility, supercritical CO2 is promising than the water by avoiding the clay hydration expansion and reducing reservoir damage. The permeability evolution influenced by the changes of the temperature and stress is the key to gas extraction in deep buried shale reservoirs. Thus, the study focuses on the coupling influence of effective stress, temperature, and CO2 adsorption expansion effects on the seepage characteristics of Silurian Longmaxi shale fractured by supercritical CO2. The results show that when the gas pressure is 1–3 MPa, the permeability decreases significantly with the increase in gas pressure, and the Klinkenberg effects plays a predominant role at this stage. When the gas pressure is 3–5 MPa, the permeability increases with the increase in gas pressure, and the influence of effective stress on permeability is dominant. The permeability decreases exponentially with the increase in effective stress. The permeability of shale after the adsorption of CO2 gas is significantly lower than that of before adsorption; the permeability decreases with the increase in temperature at 305.15 K–321.15 K, and with the increase in temperature, the permeability sensitivity to the temperature decreases. The permeability is closely related to supercritical CO2 injection pressure and volume stress; when the injection pressure of supercritical CO2 is constant, the permeability decreases with the increase in volume stress. The results can be used for the dynamic prediction of reservoir permeability and gas extraction in CO2-enhanced shale gas development.

Objectives: To establish a novel deep learning networks (MSF-MPTnet) based on panoramic radiographs (PRs) for automatic assessment of relationship between maxillary sinus floor (MSF) and maxillary posterior teeth (MPT), and to compare accuracy of MSF-MPTnet, dentists and radiologists identifying contact relationship. Study design: A total of 1035 PRs and 1035 Cone-beam computed tomographys （CBCT）images were collected from January 2018 to April 2022. The relationships were classified into class I and II by CBCT. Class I represents non-contact group, and class II represents contact group. 350 PRs were randomly selected as test dataset and accuracy of MSF-MPTnet, dentists, and radiologists was compared. Results: The intraclass correlation coefficient of dentists was 0.460–0.690 and it was 0.453–0.664 for radiologists. Sensitivity and accuracy of MSF-MPTnet were 0.682–0.852and 0.890–0.951, indicating that the output performance of MSF-MPTnet was reliable. Accuracy of maxillary premolars and molars were 79.7%–90.3 %, 76.2%–89.2 % and 72.9%–88.3 % in MSF-MPTnet model, dentists and radiologists. Accuracy of class I relationship in the MSF-MPTnet model (67.7%–94.6 %) was higher than that of dentists (56.5%–84.6 %) in maxillary first premolars and right second premolar, and accuracy of class I relationship in the MSF-MPTnet model is also higher than radiologists (40.0%–78.1 %) in all teeth positions (p

Abstract Surface modification is an important approach to improve osseointegration of the endosseous implants, however it is still desirable to develop a facile yet efficient coating strategy. Herein, a metal–phenolic network (MPN) is proposed as a multifunctional nanocoating on titanium (Ti) implants for enhanced osseointegration through early immunomodulation. With tannic acid (TA) and Sr2+ self‐assembled on Ti substrates, the MPN coatings provided a bioactive interface, which can facilitate the initial adhesion and recruitment of bone marrow mesenchymal stem cells (BMSCs) and polarize macrophage toward M2 phenotype. Furthermore, the TA‐Sr coatings accelerated the osteogenic differentiation of BMSCs. In vivo evaluations further confirmed the enhanced osseointegration of TA‐Sr modified implants via generating a favorable osteoimmune microenvironment. In general, these results suggest that TA‐Sr MPN nanocoating is a promising strategy for achieving better and faster osseointegration of bone implants, which can be easily utilized in future clinical applications.

Plant synthetic biology research requires diverse bioparts that facilitate the redesign and construction of new-to-nature biological devices or systems in plants. Limited by few well-characterized bioparts for plant chassis, the development of plant synthetic biology lags behind that of its microbial counterpart. Here, we constructed a web-based Plant Synthetic BioDatabase (PSBD), which currently categorizes 1677 catalytic bioparts and 384 regulatory elements and provides information on 309 species and 850 chemicals. Online bioinformatics tools including local BLAST, chem similarity, phylogenetic analysis, and visual strength are provided to assist with the rational design of genetic circuits for manipulation of gene expression in planta. We demonstrated the utility of the PSBD by functionally characterizing taxadiene synthase 2 and its quantitative regulation in tobacco leaves. More powerful synthetic devices were then assembled to amplify the transcriptional signals, enabling enhanced expression of flavivirus non-structure 1 proteins in plants. The PSBD is expected to be an integrative and user-centered platform that provides a one-stop service for diverse applications in plant synthetic biology research.

To address the situation that the degraded system cannot be repaired as new and the degradation is accelerated after repair in engineering practice, an imperfect condition-based maintenance model is proposed based on the Gamma process by introducing the maintenance improvement factor and the accelerated degradation factor. The maintenance improvement factor describes the recovery degree of the degradation amount after imperfect maintenance, then gives a quantitative representation method of the system maintenance improvement effect and the determination method of the maximum number of imperfect maintenance. The accelerated degradation factor is combined with the geometric process to describe the accelerated degradation process of the system after imperfect maintenance. The Monte Carlo method is used to determine the optimal number of imperfect preventive maintenance decisions. Through the demonstration of calculation examples, the influence of accelerated degradation factor and maintenance improvement factor on the long-term operation maintenance rate and the optimal number of imperfect maintenance is analyzed. The results show that the model can more comprehensively describe the degradation and maintenance process of degraded systems, and it can effectively reduce maintenance cost ratio under long-term operation. It provides a certain theoretical support for formulating an economical and reasonable maintenance strategy that is more in line with the actual degradation and maintenance process in engineering practice.

Our brain constantly processes multisensory inputs to make decisions and guide behaviors, but how goal-relevant processes are influenced by irrelevant information is unclear. Here, we investigated the effects of intermodal and intramodal task-irrelevant information on visual and auditory categorical decision-making. In both visual and auditory tasks, we manipulated the modality of irrelevant inputs (visual vs. auditory vs. none) and used linear discrimination analysis of EEG and hierarchical drift-diffusion modeling (HDDM) to identify when and how task-irrelevant information affected decision-relevant processing. The results revealed modality-specific impacts of irrelevant inputs on visual and auditory categorical decision-making. The distinct effects on the visual task were shown on the neural components, with auditory distractors amplifying the sensory processing whereas visual distractors amplifying the post-sensory process. Conversely, the distinct effects on the auditory task were shown in behavioral performance and underlying cognitive processes. Visual distractors facilitate behavioral performance and affect both stages, but auditory distractors interfere with behavioral performance and impact on the sensory processing rather than the post-sensory decision stage. Overall, these findings suggested that auditory distractors affect the sensory processing stage of both tasks while visual distractors affect the post-sensory decision stage of visual categorical decision-making and both stages of auditory categorical decision-making. This study provides insights into how humans process information from multiple sensory modalities during decision-making by leveraging modality-specific impacts.

ObjectiveTo compare the clinical outcomes of microwave-assisted intralesional curettage(MAIC) with those of en bloc resection and autogenous fibular reconstruction (EBR-AFR) for treating grade III giant cell tumor of the bone (GCTB) of the distal radius and to elucidate the indications for wrist preservation surgery.Materials and methodsIn this retrospective study, 19 patients with grade III GCTB of the distal radius who underwent surgery at three medical institutions were included and categorized based on their surgical pattern. Seven patients underwent MAIC and internal fixation with bone cement (MAIC group) and 12 underwent EBR-AFR (EBR-AFR group). To evaluate the function of the affected limb postoperatively, wrist range of motion, grip strength, Musculoskeletal Tumor Society (MSTS) scores were recorded.ResultsThe follow-up time of the MAIC group was 73.57 ± 28.61 (36–116) months, with no recurrence or lung metastasis. In contrast, the follow-up time of the EBR-AFR group was 55.67 ± 28.74 (36–132) months, with 1 case of local recurrence (8.3%, 1/12) and 1 case of lung metastasis (8.3%, 1/12). The wrist flexion, extension, supination, pronation, grip strength were better in the MAIC group than in the EBR-AFR group. Although there was no statistically significant difference in the MSTS score between the two groups, it is noteworthy that the MAIC group exhibited significantly superior emotional acceptance and hand positioning compared to the EBR-AFR group(p < 0.05).ConclusionThe functional outcomes of the MAIC group are better. The treatment strategy for grade III GCTB of the distal radius should be determined based on the specific preoperative imaging findings. Nevertheless, MAIC can be the preferred surgical approach for most patients with grade III GCTB of the distal radius, particularly for young patients.

Emerging evidence has suggested that exposure to PM2.5 is a significant contributing factor to the development of chronic obstructive pulmonary disease (COPD). However, the underlying biological effects and mechanisms of PM2.5 in COPD pathology remain elusive. In this study, we aimed to investigate the implication and regulatory effect of biomass fuels related-PM2.5 (BRPM2.5) concerning the pathological process of fibroblast-to-myofibroblast transition (FMT) in the context of COPD. In vivo experimentation revealed that exposure to biofuel smoke was associated with airway inflammation in rats. After 4 weeks of exposure, there was inflammation in the small airways, but no significant structural changes in the airway walls. However, after 24 weeks, airway remodeling occurred due to increased collagen deposition, myofibroblast proliferation, and tracheal wall thickness. In vitro, cellular immunofluorescence results showed that with stimulation of BRPM2.5 for 72 h, the cell morphology of fibroblasts changed significantly, most of the cells changed from spindle-shaped to star-shaped irregular, α-SMA stress fibers appeared in the cytoplasm and the synthesis of type I collagen increased. The collagen gel contraction experiment showed that the contractility of fibroblasts was enhanced. The expression level of TRPC1 in fibroblasts was increased. Specific siRNA-TRPC1 blocked BRPM2.5-induced FMT and reduced cell contractility. Additionally, specific siRNA-TRPC1 resulted in a decrease in the augment of intracellular Ca2+ concentration ([Ca2+]i) induced by BRPM2.5. Notably, it was found that the PI3K inhibitor, LY294002, inhibited enhancement of AKT phosphorylation level, FMT occurrence, and elevation of TRPC1 protein expression induced by BRPM2.5. The findings indicated that BRPM2.5 is capable of inducing the FMT, with the possibility of mediation by PI3K/AKT/TRPC1. These results hold potential implications for the understanding of the molecular mechanisms involved in BRPM2.5-induced COPD and may aid in the development of novel therapeutic strategies for pathological conditions characterized by fibrosis.

Background Schisandra sphenanthera Rehd. et Wils. is a plant used in traditional Chinese medicine (TCM). However, great differences exist in the content of active secondary metabolites in various parts of S. sphenanthera. Do microorganisms critically influence the accumulation of active components in different parts of S. sphenanthera? Methods In this study, 16S/ITS amplicon sequencing analysis was applied to unravel microbial communities in rhizospheric soil and different parts of wild S. sphenanthera. At the same time, the active secondary metabolites in different parts were detected, and the correlation between the secondary metabolites and microorganisms was analyzed. Results The major components identified in the essential oils were sesquiterpene and oxygenated sesquiterpenes. The contents of essential oil components in fruit were much higher than that in stem and leaf, and the dominant essential oil components were different in these parts. The dominant components of the three parts were γ-muurolene, δ-cadinol, and trans farnesol (stem); α-cadinol and neoisolongifolene-8-ol (leaf); isosapathulenol, α-santalol, cedrenol, and longiverbenone (fruit). The microbial amplicon sequences were taxonomically grouped into eight (bacteria) and seven (fungi) different phyla. Community diversity and composition analyses showed that different parts of S. sphenanthera had similar and unique microbial communities, and functional prediction analysis showed that the main functions of microorganisms were related to metabolism. Moreover, the accumulation of secondary metabolites in S. sphenanthera was closely related to the microbial community composition, especially bacteria. In endophytic bacteria, Staphylococcus and Hypomicrobium had negative effects on five secondary metabolites, among which γ-muurolene and trans farnesol were the dominant components in the stem. That is, the dominant components in stems were greatly affected by microorganisms. Our results provided a new opportunity to further understand the effects of microorganisms on the active secondary metabolites and provided a basis for further research on the sustainable utilization of S. sphenanthera.

Abstract In the face of the problem of waste disposal in the demolition of concrete structures, a composite wall composed of recycled concrete bricks and fly ash blocks was proposed, and based on the previous thermal performance research, its axial compression performance were further studied. Four types of walls were designed and constructed: (1) clay brick masonry (CBM), (2) recycled concrete brick masonry (RBM), (3) bilateral clay bricks masonry with coal-ash blocks sandwich insulation wall (CFCM), and (4) bilateral recycled concrete bricks masonry with coal-ash blocks sandwich insulation wall (RFRM). The test results showed that recycled concrete brick masonry exhibited a higher bearing capacity than clay brick masonry. The ultimate load of RBM was 15% higher than that of CBM. Moreover, the ultimate load of CFCM was 21% higher than that of CBM. Following the addition of sandwich coal-ash blocks in RBM, its ultimate load increased by over 42% than that of CBM. Following the addition of coal-ash blocks sandwich in both clay and recycled concrete bricks masonry, both the bearing capacity and strain exhibited improvement, the yielding load and compressive strength of them increased. Thus, it could be concluded that coal-ash blocks improved its bearing capacity. Based on the analysis of the axial compression tests, a theoretical computational model was developed and a computational expression to explain the compressive bearing capacity of a two-sided brick with coal-ash blocks sandwich insulation wall. Comparisons between the test ultimate loads (FT) and the estimated ultimate loads (FE) confirmed the accuracy of the theoretical calculation model for the compressive bearing capacity. Thus, theoretical computational models are highly recommended for the design of two-sided bricks with insulating walls constructed from coal-ash blocks being sandwiched together. This study provides a theoretical basis for the engineering application of recycled concrete brick wall and fly ash block composite wall.

Pentatrichomonas hominis is a trichomonad protozoan that infects the cecum and colon of humans and other mammals. It is a zoonotic pathogen that causes diarrhea in both animals and humans. As companion animals, dogs infected with P. hominis pose a risk of transmitting it to humans. Current methods, such as direct smears and polymerase chain reaction (PCR), used for P. hominis detection have limitations, including low detection rates and the need for specialized equipment. Therefore, there is an urgent need to develop rapid, sensitive, and simple detection methods for clinical application. Recombinase polymerase amplification (RPA) has emerged as a technology for rapid pathogen detection. In this study, we developed a lateral flow dipstick (LFD)-RPA method based on the highly conserved SPO11-1 gene for detecting P. hominis infection by optimizing the primers, probes, and reaction conditions, and evaluating cross-reactivity with genomes of Giardia duodenalis and other parasites. The LFD-RPA method was then used to test 128 dog fecal samples collected from Changchun. The results confirmed the high specificity of the method with no cross-reactivity with the five other parasites. The lowest detection limit of the method was 102 copies/µL, and its sensitivity was 100 times higher than that of the conventional PCR method. Consistent with the positivity rate observed using nested PCR, 12 samples (out of 128) tested positive using this method (positivity rate, 9.38%). In conclusion, the LFD-RPA method developed in this study represents a simple and sensitive assay that allows for the rapid detection of P. hominis infection in dogs, especially in this field.

Abstract Background The unicellular protozoan parasite Giardia intestinalis, which primarily infects humans and animals such as cattle and sheep, is having a major negative impact on public health. Giardia is able to evade the recognition and elimination of the host immune system because of the trophozoite surface and extracellular vesicles (EVs) covered by variant-specific surface proteins (VSPs). As key proteins for immune evasion, whether VSPs can regulate Giardia-induced pyroptosis and promote Giardia evasion of host immune responses has not been reported. Methods To examine the role of Giardia VSPAS7 on Giardia-induced activation of the signaling pathway, secretion of pro-inflammatory cytokines, pyroptosis and the mechanism involved, we constructed the pcDNA3.1-vspas7 expression plasmid and transfected this plasmid into mouse macrophages. Key proteins for pyroptosis, IL-1β secretion and LDH release were detected in pcDNA3.1-vspas7-transfected wild-type (WT) cells and NLRP3-deficient cells by western blot, ELISA and LDH assays, respectively. The interactions of Giardia VSPAS7 and mouse NLRP3 were examined using immunofluorescence assays (IFA), co-immunoprecipitation (Co-IP) and bimolecular fluorescence complementation (BiFC) assays. Results VSPAS7 could decrease the levels of phosphorylated-p65 (P-p65), P-IκBα and P-ERK caused by Giardia and reduce the production levels of Giardia-induced pro-inflammatory cytokine IL-6, IL-12 p40 and TNF-α. The results showed that VSPAS7 inhibited Giardia-mediated activation of NF-κB, ERK/MAPK signaling and secretion of pro-inflammatory cytokines. Furthermore, VSPAS7 suppressed Giardia-induced macrophage pyroptosis by reducing GSDMD cleavage, caspase-1 activation, IL-1β secretion and LDH release. We further found that VSPAS7 could interact with mouse NLRP3 directly, and in NLRP3-deficient cells the suppression of Giardia-induced macrophage pyroptosis by VSPAS7 was significantly attenuated. Conclusions Overall, VSPAS7 could inhibit Giardia-induced activation of signaling pathways and pyroptosis in host macrophages, allowing Giardia evasion of host immune responses. Studies on Giardia VSP-mediated immune evasion provide an important theoretical basis for in-depth studies on Giardia pathogenicity. Graphical abstract

Abstract Background Explaining contrasting patterns of distribution between related species is crucial for understanding the dynamics of biodiversity. Despite instances where hybridization and whole genome duplication (WGD) can yield detrimental outcomes, a role in facilitating the expansion of distribution range has been proposed. The Vitaceae genus Causonis exhibits great variations in species’ distribution ranges, with most species in the derived lineages having a much wider range than those in the early-diverged lineages. Hybridization and WGD events have been suggested to occur in Causonis based on evidence of phylogenetic discordance. The genus, therefore, provides us with an opportunity to for explore different hybridization and polyploidization modes in lineages with contrasting species’ distribution ranges. However, the evolutionary history of Causonis incorporating potential hybridization and WGD events remains to be explored. Results With plastid and nuclear data from dense sampling, this study resolved the phylogenetic relationships within Causonis and revealed significant cyto-nuclear discordance. Nuclear gene tree conflicts were detected across the genus, especially in the japonica-corniculata clade, which were mainly attributed to gene flow. This study also inferred the allopolyploid origin of the core Causonis species, which promoted the accumulation of stress-related genes. Causonis was estimated to have originated in continental Asia in the early Eocene, and experienced glaciation in the early Oligocene, shortly after the divergence of the early-divergent lineages. The japonica-corniculata clade mainly diversified in the Miocene, followed by temperature declines that may have facilitated secondary contact. Species distribution modeling based on current climate change predicted that the widespread C. japonica tends to be more invasive, while the endemic C. ciliifera may be at risk of extinction. Conclusions This study presents Causonis, a genus with complex reticulate evolutionary history, as a model of how hybridization and WGD modes differ in lineages of contrasting species’ geographic ranges. It is important to consider specific evolutionary histories and genetic properties of the focal species within conservation strategies.

This paper investigates the problem of coordinated resource allocation for multiple unmanned aerial vehicles (UAVs) to address the scarcity of communication resources in disaster-affected areas. UAVs carrying modules of free space optical (FSO) and radio frequency (RF) serve as relay nodes and edge offloading nodes, presenting an FSO/RF dual-hop framework. Considering the varying urgency levels of tasks, we assign task priorities and transform the proposed problem into distributed collaborative optimization problem. Based on the K-means algorithm and the multi-agent deep deterministic policy gradient (MADDPG) algorithm, we propose a UAV-coordinated K-means MADDPG (KMADDPG) to maximize the number of completed tasks while prioritizing high-priority tasks. Simulation results show that KMADDPG is 5% to 10% better than the benchmark DRL methods in convergence performance.

Wetland ecosystems in the Qinghai-Tibet Plateau (QTP), the region with the richest biodiversity and the most important ecological barrier function at high altitudes, are highly sensitive to global change, and wetland plants, which are important indicators of wetland ecosystem structure and function, are also threatened by wetland degradation. Therefore, a comprehensive study of changes in the geographical distribution pattern of plant diversity, as well as species loss and turnover of wetlands in the QTP in the context of global climate change is of great importance for the conservation and restoration of wetland ecosystems in the QTP. In this study, species turnover and loss of 395 endemic wetland plants of the QTP were predicted based on the SSP2-4.5 climate change scenarios. The results showed that there were interspecific differences in the effects of climate change on the potential distribution of species, and that most endemic wetland plants would experience range contraction. Under the climate change scenarios, the loss of suitable wetland plant habitat is expected to occur mainly in parts of the southern, north-central and north-western parts of the plateau, while the gain is mainly concentrated in parts of the western Sichuan Plateau, the Qilian Mountains, the Three Rivers Source Region and the northern Tibetan Plateau. Overlaying the analysis of priority protected areas with the established protected areas in the QTP has resulted in the following conservation gaps: the eastern Himalayan region, midstream of the Yarlung Zangbo River, the transition zone between the northern Tibetan Plateau and the Hengduan Mountains, Minshan-Qionglai mountain, Anyemaqen Mountains (southeast) to Bayankala (southeast) mountains, the southern foothills of the Qilian Mountains and the northern Tibetan Plateau region. In the future, the study of wetland plant diversity in the QTP and the optimisation of protected areas should focus on the conservation gaps. This study is of great importance for the study and conservation of wetland plant diversity in the QTP, and also provides a scientific basis for predicting the response of wetland plants to climate change in the QTP.

Long-term series monitoring of ground surface settlement by remote sensing has become an effective method. Based on TS-InSAR (time series Interferometric Synthetic Aperture Radar) interferometry, this paper proposes a new model based on the Grey Wolf Optimizer (GWO) and Long Short-Term Memory (LSTM) to monitor and predict the ground surface settlement in Kunming City. The results show that the MAPE (mean absolute percentage error), RMSE (root mean square error), and MAE (mean absolute error) of GWO-LSTM are significantly reduced. R2 (goodness of fit) in the six sub-study areas of Kunming City is improved in comparison to the LSTM model. The problem of manual parameter selection in the LSTM model is solved by the GWO algorithm to select parameters automatically. This approach not only significantly reduces the model’s training time but also identifies the most suitable network parameters. This can bring the best performance. Based on TS-InSAR data, the prediction of urban ground surface settlement by the GWO-LSTM model has good accuracy and robustness, which offers a scientific foundation for monitoring and issuing early warnings about urban land disasters.

Abstract Background Low back pain (LBP) is the main factor of global disease burden. Intervertebral disc degeneration (IVDD) has long been known as the leading reason of LBP. Increasing studies have verified that circular RNAs (circRNAs)‐microRNAs (miRNAs)‐mRNAs network is widely involved in the pathological processes of IVDD. However, no study was made to demonstrate the circRNAs‐mediated ferroptosis, oxidative stress, extracellular matrix metabolism, and immune response in IVDD. Methods We collected 3 normal and 3 degenerative nucleus pulposus tissues to conduct RNA‐sequencing to identify the key circRNAs and miRNAs in IVDD. Bioinformatics analysis was then conducted to construct circRNAs‐miRNAs‐mRNAs interaction network associated with ferroptosis, oxidative stress, extracellular matrix metabolism, and immune response. We also performed animal experiments to validate the therapeutic effects of key circRNAs in IVDD. Results We found that circ_0015435 was most obviously upregulated and circ_0071922 was most obviously downregulated in IVDD using RNA‐sequencing. Then we observed that hsa‐miR‐15a‐5p was the key downstream of circ_0071922, and hsa‐miR‐15a‐5p was the top upregulated miRNA in IVDD. Bioinformatics analysis was conducted to predict that 56 immunity‐related genes, 29 ferroptosis‐related genes, 23 oxidative stress‐related genes and 8 ECM‐related genes are the targets mRNAs of hsa‐miR‐15a‐5p. Then we constructed a ceRNA network encompassing 24 circRNAs, 6 miRNAs, and 101 mRNAs. Additionally, we demonstrated that overexpression of circ_0071922 can alleviate IVDD progression in a rat model. Conclusions The findings of this study suggested that circ_0071922‐miR‐15a‐5p‐mRNA signaling network might affect IVDD by modulating the nucleus pulposus cells ferroptosis, oxidative stress, ECM metabolism, and immune response, which is an effective therapeutic targets of IVDD.

The 2019 novel coronavirus, SARS-CoV-2, was highly prevalent in China as of December 2022, causing a range of symptoms, predominantly affecting the respiratory tract. While SARS-CoV-2 infection in children is generally mild, severe cases, especially in infants, are rare. We present a case of a previously healthy 7-month-old infant who developed cerebral infarction and coagulation dysfunction three days after COVID-19 onset. Clinically, the infant had weakness in the left limbs and pinpoint bleeding spots. A cranial magnetic resonance imaging showed ischemic strokes in the right basal ganglia and thalamus. Laboratory tests indicated thrombocytopenia and coagulation dysfunction. Inflammatory cytokines like interleukin-10 were elevated, with increased CD3+, CD4+, and CD8+ T lymphocytes but decreased CD3- CD16+ CD56+ natural killer cells. Treatment included mannitol, dexamethasone, oral aspirin, and vitamins B1 and B6 for reducing intracranial pressure, antiinflammation, anticoagulation, and nerve support, respectively. During the recovery phase, rehabilitation therapy focused on strength training, fine motor skills, and massage therapy. The infant gradually improved and successfully recovered. While rare, such cases can lead to severe complications. These combined efforts were instrumental in achieving significant functional recovery in the patient, demonstrating that even in severe instances of pediatric cerebral infarction due to COVID-19, positive outcomes are attainable with early and comprehensive medical response.

The pathogenic mechanisms of bacterial infections and resultant sepsis are partly attributed to dysregulated inflammatory responses sustained by some late-acting mediators including the procathepsin-L (pCTS-L). It was entirely unknown whether any compounds of the U.S. Drug Collection could suppress pCTS-L-induced inflammation, and pharmacologically be exploited into possible therapies. Here, we demonstrated that a macrophage cell-based screening of a U.S. Drug Collection of 1360 compounds resulted in the identification of progesterone (PRO) as an inhibitor of pCTS-L-mediated production of several chemokines [e.g., Epithelial Neutrophil-Activating Peptide (ENA-78), Monocyte Chemoattractant Protein-1 (MCP-1) or MCP-3] and cytokines [e.g., Interleukin-10 (IL-10) or Tumor Necrosis Factor (TNF)] in primary human peripheral blood mononuclear cells (PBMCs). In vivo, these PRO-entrapping 2,6-dimethal-β-cyclodextrin (DM-β-CD) nanoparticles (containing 1.35 mg/kg PRO and 14.65 mg/kg DM-β-CD) significantly increased animal survival in both male (from 30% to 70%, n = 20, P = 0.041) and female (from 50% to 80%, n = 30, P = 0.026) mice even when they were initially administered at 24 h post the onset of sepsis. This protective effect was associated with a reduction of sepsis-triggered accumulation of three surrogate biomarkers [e.g., Granulocyte Colony Stimulating Factor (G-CSF) by 40%; Macrophage Inflammatory Protein-2 (MIP-2) by 45%; and Soluble Tumor Necrosis Factor Receptor I (sTNFRI) by 80%]. Surface Plasmon Resonance (SPR) analysis revealed a strong interaction between PRO and pCTS-L (KD = 78.2 ± 33.7 nM), which was paralleled with a positive correlation between serum PRO concentration and serum pCTS-L level (ρ = 0.56, P = 0.0009) or disease severity (Sequential Organ Failure Assessment, SOFA; ρ = 0.64, P = 0.0001) score in septic patients. Our observations support a promising opportunity to explore DM-β-CD nanoparticles entrapping lipophilic drugs as possible therapies for clinical sepsis.

Abstract A feature of peripheral artery diseases (PAD) includes limb ischemia/reperfusion (I/R) and ischemia. Both I/R and ischemia amplify muscle afferent nerve‐activated reflex sympathetic nervous and blood pressure responses (termed as exercise pressor reflex). Nevertheless, the underlying mechanisms responsible for the exaggerated autonomic responses in PAD are undetermined. Previous studies suggest that acid‐sensing ion channels (ASICs) in muscle dorsal root ganglion (DRG) play a leading role in regulating the exercise pressor reflex in PAD. Thus, we determined if signaling pathways of nerve growth factor (NGF) contribute to the activities of ASICs in muscle DRG neurons of PAD. In particular, we examined ASIC1a and ASIC3 currents in isolectin B4‐negative muscle DRG neurons, a distinct subpopulation depending on NGF for survival. Hindlimb I/R and ischemia were obtained in male rats. In results, femoral artery occlusion increased the levels of NGF and NGF‐stimulated TrkA receptor in DRGs, whereas they led to upregulation of ASIC3 but not ASIC1a. In addition, application of NGF onto DRG neurons increased the density of ASIC3 currents and the effect of NGF was significantly attenuated by TrkA antagonist GW441756. Moreover, the enhancing effect of NGF on the density of ASIC3‐like currents was decreased by the respective inhibition of intracellular signaling pathways, namely JNK and NF‐κB, by antagonists SP600125 and PDTC. Our results suggest contribution of NGF to the activities of ASIC3 currents via JNK and NF‐κB signaling pathways in association with the exercise pressor reflex in experimental PAD.

Mitochondria-associated membrane (MAM) serve as crucial contact sites between mitochondria and the endoplasmic reticulum (ER). Recent research has highlighted the significance of MAM, which serve as a platform for various protein molecules, in processes such as calcium signaling, ATP production, mitochondrial structure and function, and autophagy. Cardiac diseases caused by any reason can lead to changes in myocardial structure and function, significantly impacting human health. Notably, MAM exhibits various regulatory effects to maintain cellular balance in several cardiac diseases conditions, such as obesity, diabetes mellitus, and cardiotoxicity. MAM proteins independently or interact with their counterparts, forming essential tethers between the ER and mitochondria in cardiomyocytes. This review provides an overview of key MAM regulators, detailing their structure and functions. Additionally, it explores the connection between MAM and various cardiac injuries, suggesting that precise genetic, pharmacological, and physical regulation of MAM may be a promising strategy for preventing and treating heart failure.

Heat stroke (HS) is a febrile illness characterized by an elevation in the core body temperature to over 40°C, accompanied by central nervous system impairment and subsequent multi-organ dysfunction syndrome. In recent years, the mortality rate from HS has been increasing as ambient temperatures continue to rise each year. The cardiovascular system plays an important role in the pathogenesis process of HS, as it functions as one of the key system for thermoregulation and its stability is associated with the severity of HS. Systemic inflammatory response and endothelial cell damage constitute pivotal attributes of HS, other factors such as ferroptosis, disturbances in myocardial metabolism and heat shock protein dysregulation are also involved in the damage to myocardial tissue in HS. In this review, a comprehensively detailed description of the pathogenesis of HS-induced myocardial injury is provided. The current treatment strategies and the promising therapeutic targets for HS are also discussed.

Abstract BackgroundAlthough evidence-based medicine proposes personalized care that considers the best evidence, it still fails to address personal treatment in many real clinical scenarios where the complexity of the situation makes none of the available evidence applicable. “Medicine-based evidence” (MBE), in which big data and machine learning techniques are embraced to derive treatment responses from appropriately matched patients in real-world clinical practice, was proposed. However, many challenges remain in translating this conceptual framework into practice. ObjectiveThis study aimed to technically translate the MBE conceptual framework into practice and evaluate its performance in providing general decision support services for outcomes after congenital heart disease (CHD) surgery. MethodsData from 4774 CHD surgeries were collected. A total of 66 indicators and all diagnoses were extracted from each echocardiographic report using natural language processing technology. Combined with some basic clinical and surgical information, the distances between each patient were measured by a series of calculation formulas. Inspired by structure-mapping theory, the fusion of distances between different dimensions can be modulated by clinical experts. In addition to supporting direct analogical reasoning, a machine learning model can be constructed based on similar patients to provide personalized prediction. A user-operable patient similarity network (PSN) of CHD called CHDmap ResultsUsing 256 CHD cases, CHDmap was evaluated on 2 different types of postoperative prognostic prediction tasks: a binary classification task to predict postoperative complications and a multiple classification task to predict mechanical ventilation duration. A simple poll of the k ConclusionsWithout individual optimization, CHDmap demonstrates competitive performance compared to clinical experts. In addition, CHDmap has the advantage of enabling clinicians to use their superior cognitive abilities in conjunction with it to make decisions that are sometimes even superior to those made using artificial intelligence models. The MBE approach can be embraced in clinical practice, and its full potential can be realized.

Electromagnetic loads can effectively monitor motor health and improve motor design. Considering the weak correlation of the modal shape and Chebyshev orthogonal polynomial in the space-time independent electromagnetic load identification method, a proposed method combining the polynomial structure selection technique together with limited measured displacement responses is presented, in which an error reduction ratio is used to pick out the significant mode shape matrix and the Chebyshev orthogonal polynomial. The time-history function of the electromagnetic load is reconstructed by combining the significant mode shape matrix and the identified concentrated load through modal transformation, and the corresponding spatial distribution function is fitted by the significant Chebyshev orthogonal polynomial. Eventually, a comparative numerical study considering the selection of significant components and measurement noise is carried out to prove the effectiveness of the presented method.

Hypertension constitutes a pervasive chronic ailment on a global scale, frequently inflicting damage upon vital organs, such as the heart, blood vessels, kidneys, brain, and others. And this is a complex clinical dilemma that requires immediate attention. The mitochondria assume a crucial function in the generation of energy, and it is of utmost importance to eliminate any malfunctioning or surplus mitochondria to uphold intracellular homeostasis. Mitophagy is considered a classic example of selective autophagy, an important component of mitochondrial quality control, and is closely associated with many physiological and pathological processes. The ubiquitin-dependent pathway, facilitated by PINK1/Parkin, along with the ubiquitin-independent pathway, orchestrated by receptor proteins such as BNIP3, NIX, and FUNDC1, represent the extensively investigated mechanisms underlying mitophagy. In recent years, research has increasingly shown that mitophagy plays an important role in organ damage associated with hypertension. Exploring the molecular mechanisms of mitophagy in hypertension-mediated organ damage could represent a critical avenue for future research in the development of innovative therapeutic modalities. Therefore, this article provides a comprehensive review of the impact of mitophagy on organ damage due to hypertension.

Abstract Background and aims This study aimed to investigate the association between the Dietary Inflammatory Index (DII) and dyslipidemia, as well as to evaluate the mortality risk associated with DII in participants with dyslipidemia. Methods Data from the National Health and Nutrition Examination Survey database were divided into dyslipidemia and non-dyslipidemia groups. The association between DII and dyslipidemia was investigated using the weighted chi-square test, weighted t-test, and weighted logistic regression. Weighted Cox proportional hazards models were used to estimate the hazard ratios and 95% confidence intervals for all-cause and cardiovascular disease-related mortality within the dyslipidemia group. Results A total of 17,820 participants, including 4,839 without and 12,981 with dyslipidemia were analyzed in this study. The results showed that DII was higher in the dyslipidemia group compared to the non-dyslipidemia group (1.42 ± 0.03 vs. 1.23 ± 0.04, P

Abstract A risk association between membranous nephropathy (MN) and lung cancer is reported, but traditional observational studies cannot provide strong evidence of its causality. This study aimed to assess genome-wide association studies data for a causal relationship between MN and lung cancer using a two-sample Mendelian randomization (MR) approach. Inverse-variance weighted, and MR Egger regression techniques were used to determine the association of genetic variants from cohorts of MN and lung cancer patients. Independent genetic variants with genome-wide significance (P

Objective To investigate the resource allocation status of blood testing laboratories in 14 blood stations in Gansu Province, explore the impact of differences in basic conditions on the comprehensive testing ability of laboratories, so as to promote the homogenization and standardization of blood screening capacity in blood stations in Gansu and improve blood safety and effectivenes. Methods An evaluation index system of laboratory resource allocation was constructed and a question-naire was designed. The data of human resources, infrastructure and key equipment of 14 blood stations were collected. The entropy weight -TOPSIS method was used to evaluate and rank the resource allocation of 14 blood stations. Results In the comprehensive evaluation of blood testing laboratory resource allocation in 14 blood stations in Gansu, the top three were laboratories A, B and I, and the last three were laboratories G, M and J. On the whole, the main issue was unreasonable structure of human resources: most laboratories had unreasonable age structure; except for Laboratory A, there was no personnel with bachelor's degree or above in laboratories; most laboratories had not established a team with intermediate professional titles. In terms of infrastructure, the size of seven laboratories could not meet the needs of modern laboratory testing, and all eight blood stations had no spare nucleic acid laboratories nor a mutual spare laboratory with other blood stations As for the key equipment, 5 laboratories had no automatic blood grouping diagnostic instrument, 5 laboratories only had one set of enzyme immunoassay detection system, 3 laboratories had no spare equipment for the key equipment, which means if the equipment failure could not be repaired in time, the release of results would be affected. Conclusion There were significant differences in human resources, infrastructure and key equipment of blood testing laboratories in 14 blood stations in Gansu, which had a great impact on laboratory testing capacity and subsequent development. It is suggested that governments at all levels and health administrative departments optimize the input of laboratory resource allocation according to the blood collection volume of blood stations to gradually narrow the differences in resource distribution between different regions, improve the degree of laboratory automation and optimize the personnel structure, so as to build high-quality and efficient blood testing laboratories and ensure the safety of clinical blood use.

To optimize the technical condition for purification of tea polyphenols with macroporous adsorption resin, the static adsorption and desorption performance of macroporous adsorption resin of fourteen types were compared to select the best type of resin. The optimal purification process conditions were determined by single factor and response surface experiments, and the reuse and regeneration times of the resin were further investigated. Meanwhile, the antioxidant activities of tea polyphenols before and after purification were investigated by in vitro experiments with VC as the control. The results showed that LX-8 resin had the best adsorption-desorption effect on tea polyphenols, which could be reused 5 times and regenerated 6 times. The optimum purification conditions were as below: The sample concentration of 6.4 mg/mL, the sample pH value of 5.4, the loading volume of 100 mL, the sample flow rate of 1.0 mL/min, ethanol concentration of 76% eluting agent volume of 180 mL, and desorption rate of 1.0 mL/min. Under these conditions, the recovery rate of tea polyphenols was 86.9% and the purity was 74.6%. In vitro antioxidant activity studies revealed that the total antioxidant capacity, DPPH· scavenging capacity and ·OH scavenging capacity of the purified tea polyphenols were significantly increased. And with the increase of polyphenol concentration, its antioxidant capacity enhanced. The total antioxidant capacity of the purified tea polyphenol (1 mg/mL) was 80.59 U/mL. The IC50 of the purified tea polyphenol on scavenging ability of DPPH· and ·OH were 0.0326 and 0.4167 mg/mL respectively. Although the antioxidant activity of pure extract was lower than that of VC, it was higher than that of crude extract, indicating that the antioxidant activity of tea polyphenols could be significantly improved by this process, and when the concentration of the purified tea polyphenol was 1 mg/mL, its DPPH· scavenging rate was close to that of VC. This research provided a theoretical reference for the industrial production and utilization of tea polyphenols.