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Identifying priority conservation areas (PCAs) on the basis of ecosystem services (ESs) trade-offs is a crucial step in achieving optimal ecosystem management in the BTH, noting the complex spatio-temporal and scaling effects inherent in these ecosystems. A cross-scale quantification of spatial and temporal changes in ecosystem services and their correlations was conducted in the BTH. Furthermore, the Ordered Weighting Algorithm (OWA) was introduced to simulate a variety of scenarios in order to determine the PCAs and to explore the drivers of ES in the PCAs. The results indicated that Food supply (FS), Water yield (WY), and Soil retention (SR) in the BTH increased by 16.4 × 104t/hm2, 81.81 mm, and 37081.29 t/hm2, respectively. In contrast, Carbon storage (CS) and Habit quality (HQ) exhibited a decrease of 0.01 t/hm2 and 0.03. Spatially, the high-value areas of ESs at the county scale exhibited greater clustering. At the county scale, there were two trade-offs and eight synergies in 2000, and four trade-offs and six synergies by 2020. In contrast, at the raster scale, there were two trade-offs and eight synergies from 2000 to 2020. The mechanisms of change were similar and exhibited spatial heterogeneity. Scenario 6 represents the optimal priority conservation area, exhibiting the most balanced conservation efficiency of each ecosystem service. This scenario enables the simultaneous conservation of multiple ESs. The natural factors within the PCAs exert a stronger influence on ESs than socio-economic factors. The inclusion of interacting factor effects will enhance the explanatory power of the drivers. The findings of this study can serve as a theoretical foundation for cross-scale ecosystem service management decisions.

IntroductionAlzheimer’s disease (AD) is highly heterogeneous, with substantial individual variabilities in clinical progression and neurobiology. Amyloid deposition has been thought to drive cognitive decline and thus a major contributor to the variations in cognitive deterioration in AD. However, the clinical heterogeneity of patients with early symptomatic AD (mild cognitive impairment or mild dementia due to AD) already with evidence of amyloid abnormality in the brain is still unknown.MethodsParticipants with a baseline diagnosis of mild cognitive impairment or mild dementia, a positive amyloid-PET scan, and more than one follow-up Alzheimer’s Disease Assessment Scale-Cognitive Subscale-13 (ADAS-Cog-13) administration within a period of 5-year follow-up were selected from the Alzheimer’s Disease Neuroimaging Initiative database (n = 421; age = 73±7; years of education = 16 ± 3; percentage of female gender = 43%; distribution of APOE4 carriers = 68%). A non-parametric k-means longitudinal clustering analysis in the context of the ADAS-Cog-13 data was performed to identify cognitive subtypes.ResultsWe found a highly variable profile of cognitive decline among patients with early AD and identified 4 clusters characterized by distinct rates of cognitive progression. Among the groups there were significant differences in the magnitude of rates of changes in other cognitive and functional outcomes, clinical progression from mild cognitive impairment to dementia, and changes in markers presumed to reflect neurodegeneration and neuronal injury. A nomogram based on a simplified logistic regression model predicted steep cognitive trajectory with an AUC of 0.912 (95% CI: 0.88 – 0.94). Simulation of clinical trials suggested that the incorporation of the nomogram into enrichment strategies would reduce the required sample sizes from 926.8 (95% CI: 822.6 – 1057.5) to 400.9 (95% CI: 306.9 – 516.8).DiscussionOur findings show usefulness in the stratification of patients in early AD and may thus increase the chances of finding a treatment for future AD clinical trials.

Abstract Pluripotent stem cell‐derived small extracellular vesicles (PSC‐sEVs) have demonstrated great clinical translational potential in multiple aging‐related degenerative diseases. Characterizing the PSC‐sEVs is crucial for their clinical applications. However, the specific marker pattern of PSC‐sEVs remains unknown. Here, the sEVs derived from two typical types of PSCs including induced pluripotent stem cells (iPSC‐sEVs) and embryonic stem cells (ESC‐sEVs) were analysed using proteomic analysis by liquid chromatography with tandem mass spectrometry (LC‐MS/MS), and surface marker phenotyping analysis by nanoparticle flow cytometry (NanoFCM). A group of pluripotency‐related proteins were found to be enriched in PSC‐sEVs by LC‐MS/MS and then validated by Western Blot analysis. To investigate whether these proteins were specifically expressed in PSC‐sEVs, sEVs derived from seven types of non‐PSCs (non‐PSC‐sEVs) were adopted for analysis. The results showed that PODXL, OCT4, Dnmt3a, and LIN28A were specifically enriched in PSC‐sEVs but not in non‐PSC‐sEVs. Then, commonly used surface antigens for PSC identification (SSEA4, Tra‐1‐60 and Tra‐1‐81) and PODXL were gauged at single‐particle resolution by NanoFCM for surface marker identification. The results showed that the positive rates of PODXL (>50%) and SSEA4 (>70%) in PSC‐sEVs were much higher than those in non‐PSC‐sEVs (

Abstract Background Given the complex and progressive nature of mild cognitive impairment (MCI), the ability to delineate and understand the heterogeneous cognitive trajectories is crucial for developing personalized medicine and informing trial design. The primary goals of this study were to examine whether different cognitive trajectories can be identified within subjects with MCI and, if present, to characterize each trajectory in relation to changes in all major Alzheimer’s disease (AD) biomarkers over time. Methods Individuals with a diagnosis of MCI at the first visit and ≥ 1 follow-up cognitive assessment were selected from the Alzheimer’s Disease Neuroimaging Initiative database (n = 936; age 73 ± 8; 40% female; 16 ± 3 years of education; 50% APOE4 carriers). Based on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale-13 (ADAS-Cog-13) total scores from baseline up to 5 years follow-up, a non-parametric k-means longitudinal clustering method was performed to obtain clusters of individuals with similar patterns of cognitive decline. We further conducted a series of linear mixed-effects models to study the associations of cluster membership with longitudinal changes in other cognitive measures, neurodegeneration, and in vivo AD pathologies. Results Four distinct cognitive trajectories emerged. Cluster 1 consisted of 255 individuals (27%) with a nearly non-existent rate of change in the ADAS-Cog-13 over 5 years of follow-up and a healthy-looking biomarker profile. Individuals in the cluster 2 (n = 336, 35%) and 3 (n = 240, 26%) groups showed relatively mild and moderate cognitive decline trajectories, respectively. Cluster 4, comprising about 11% of our study sample (n = 105), exhibited an aggressive cognitive decline trajectory and was characterized by a pronouncedly abnormal biomarker profile. Conclusions Individuals with MCI show substantial heterogeneity in cognitive decline. Our findings may potentially contribute to improved trial design and patient stratification.

Tendinopathy is a common musculoskeletal disorder which results in chronic pain and reduced performance. The therapeutic effect of stem cell derived-small extracellular vesicles (sEVs) for tendinopathy has been validated in recent years. However, whether large extracellular vesicles (lEVs), another subset of extracellular vesicles, possesses the ability for the improvement of tendinopathy remains unknown. Here, we showed that lEVs secreted from iPSC-derived MSCs (iMSC-lEVs) significantly mitigated pain derived from tendinopathy in rats. Immunohistochemical analysis showed that iMSC-lEVs regulated the heterogeneity of infiltrated macrophages and several inflammatory cytokines in rat tendon tissue. Meanwhile, in vitro experiments revealed that the M1 pro-inflammatory macrophages were repolarized towards M2 anti-inflammatory macrophages by iMSC-lEVs, and this effect was mediated by regulating p38 MAPK pathway. Moreover, liquid chromatography-tandem mass spectrometry analysis identified 2208 proteins encapsulated in iMSC-lEVs, including 134 new-found proteins beyond current Vesiclepedia database. By bioinformatics and Western blot analyses, we showed that DUSP2 and DUSP3, the negative regulator of p38 phosphorylation, were enriched in iMSC-lEVs and could be transported to macrophages. Further, the immunomodulatory effect of iMSC-lEVs on macrophages was validated in explant tendon tissue from tendinopathy patients. Taken together, our results demonstrate that iMSC-lEVs could reduce inflammation in tendinopathy by regulating macrophage heterogeneity, which is mediated via the p38 MAPK pathway by delivery of DUSP2 and DUSP3, and might be a promising candidate for tendinopathy therapy.

The closed-form solution of each rotation joint angle is the most direct and convenient method for humanoid robot arms to imitate the real-time motion of the human arm. Occasionally, the human structure differs from that of a robot, and sensor information is inadequate. Therefore, it is difficult to obtain a closed-form solution for the inverse kinematics (IK) of a robot when using the Denavit–Hartenberg (D–H) method or screw theory alone. This study proposes combining the screw theory and the D–H method to solve the closed-form solution of the IK of a robotic arm with two unique structures: the elbow joint offset and the non-vertical state at the shoulder joint of the robotic arm. The proposed combination method first solves the elbow joint angle using screw theory. Then, the other rotation joint angles are solved using the D–H method. With the proposed method, human arm motion is successfully mapped to the corresponding joint of the robotic arm, and the closed-form solution allows the robotic arm to imitate human arm motion in real–time. Simulation results show that IK can be used to obtain high–precision angles and positions. Experiments show that the robotic arm has an accurate imitation performance, the accuracy of the $z$ -axis of the manipulator is significantly improved by 73.6%, and that of the $x$ -axis and $y$ -axis is also improved by 37.36% and 21.89%, respectively.

Abstract Small extracellular vesicles derived from human pluripotent stem cells (hPSC‐sEVs) have shown great application potential in regenerative medicine. To standardise its research and clinical application, the first set of guidelines on hPSC‐sEVs in China ‘Requirements for human pluripotent stem cell derived small extracellular vesicles’ was released by the Chinese Research Hospital Association on 28 December 2021 and came into effect on 1 January 2022. It was jointly drafted and agreed upon by the experts from the Chinese Society of Extracellular Vesicles. This standard specifies the technical requirements, test methods and regulations, packaging, instructions for use, labelling, storage, transportation, and waste handling for hPSC‐sEVs, which apply to the production and quality control of hPSC‐sEVs. We hope that the publication of these guidelines will make it one step closer to international standardisation of hPSC‐sEVs for research and application.

Background: Right ventricle-pulmonary arterial (RV-PA) coupling is considered the gold standard for assessing right ventricular (RV) function and can be evaluated noninvasively by echocardiography. The ratios of tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP), RV global longitudinal strain (G-RVLS)/PASP, and stroke volume/end-systolic volume (SV/ESV) have been proposed as surrogates of RV-PA coupling. The relationship of these parameters remains incompletely understood in patients with volume and pressure loading conditions. We aimed to compare these parameters and evaluate their relationship with 3D RV data in patients with RV pressure and volume overload. Methods: This study was performed on 110 individuals who underwent 2D and 3D echocardiography. Fifty-four patients had RV volume overload (atrial septal defect (ASD) group), 34 patients had RV pressure overload (pulmonary hypertension (PH) group), and 22 were controls. TAPSE/PASP, G-RVLS/PASP and SV/ESV ratios were calculated. Correlations between parameters of RV-PA coupling and 3D data were assessed using general linear mixed models. Results: Compared with the ASD group, the PH group had lower TAPSE/PASP and G-RVLS/PASP ratios. The SV/ESV ratio had a strong correlation with right ventricle ejection fraction (RVEF) in both ASD and PH patients (r = 0.8703, p < 0.001 and r = 0.9388, p < 0.001, respectively). The G-RVLS/PASP ratio showed a strong or moderately negative relationship with end-diastolic volume (EDV), ESV and SV (r = –0.7768, p = 0.001; r = –0.7327, p = 0.0005 and r = –0.6816, p = 0.0018, respectively) in PH patients. The TAPSE/PASP ratio showed moderately negative correlations with EDV and ESV (r = –0.5712, p = 0.0012 and r = –0.5594, p = 0.0016, respectively) in PH patients. Conclusions: Non-invasive RV-PA coupling parameters derived from echocardiography appear similar, but not identical to profiles in pressure-overloaded and volume-overloaded patients. The correlations between non-invasive RV-PA coupling parameters and 3D data displayed various degrees of correlation.

Abstract “Requirements for human mesenchymal stem cell‐derived small extracellular vesicles” is the first set of guidelines on human mesenchymal stem cell‐derived small extracellular vesicles (hMSC‐sEVs) in China, jointly drafted and agreed upon by experts from the Chinese Society for Extracellular Vesicles. It was released by the Chinese Research Hospital Association on 28 December 2021 and came into effect on 1 January 2022. This standard specifies the technical requirements, test methods and regulations, packaging, instructions for use, labeling, storage, transportation, and waste handling for hMSC‐sEVs, which apply to the production and quality control of hMSC‐sEVs. We hope that the publication of these guidelines will promote consensus on the research and application of human mesenchymal stem cell‐derived small extracellular vesicles and accelerate its international standardization.

Yushu Tibetan Autonomous Prefecture is located in the Three Rivers Source area, which is known as the "water tower of China". However, due to the restriction of natural conditions, the ecological environment of Yushu Prefecture is extremely fragile and its self-recovery ability is poor. Based on the DPSIR concept model, this study collected the ecological environment and socio-economic data of Yushu Tibetan Autonomous Prefecture in 2000, 2005, 2010 and 2015, and established a dynamic evaluation model of ecological security by using expert scoring method and analytic hierarchy process. The weights of each index are determined and the data are standardized to analyze the temporal and spatial changes of ecological security in Yushu area. The results show that the change range of ecological security in Yushu Prefecture is less than 5%, and there is a weak tendency to develop to both ends. In terms of space, the ecological security situation in the southeast of Yushu Prefecture is better than that in the northwest, showing the distribution characteristics of insecurity in the northwest, early warning in the middle and safety in the southeast.

The lubricating oil heat diffusion ejector of a certain aircraft engine under the condition of engine idling on ground in the hot weather has the problem of low lubricating oil temperature drop after its turning on. The flow process of cool-side air flue of lubricating oil heat diffusion system is analyzed, and the ejector performance analysis method under severe conditions is explored. Based on N-S equations and k-ε turbulence model, the ejector performance is calculated and verified by test, and the lubricating oil temperature drop values before/after ejector turning on under severe conditions are obtained. The improvement scheme of ejector performance available in engineering is proposed on the basis of numerical calculation results. The results of the on-board ground test show that the calculation method is reasonable, and numerical simulation results are consistent with the test results, which meets the requirements of general engineering calculations, and provides a theoretical method for the performance analysis of an ejector.

ObjectiveThere is growing evidence that testosterone may be implicated in the pathogenesis of Alzheimer’s disease (AD). We aimed to examine the relationship between plasma total testosterone levels and change in brain glucose metabolism over time among non-demented older people.MethodsThe association of plasma total testosterone levels with change in brain glucose metabolism among non-demented older people was investigated cross-sectionally and longitudinally. Given a significant difference in levels of plasma total testosterone between gender, we performed our analysis in a sex-stratified way. At baseline, 228 non-demented older people were included: 152 males and 76 females.ResultsIn the cross-sectional analysis, no significant relationship between plasma total testosterone levels and brain glucose metabolism was found in males or females. In the longitudinal analysis, we found a significant association of plasma total testosterone levels with change in brain glucose metabolism over time in males, but not in females. More specifically, in males, higher levels of total testosterone in plasma at baseline were associated with slower decline in brain glucose metabolism.ConclusionWe found that higher levels of total testosterone in plasma at baseline were associated with slower decline in brain glucose metabolism in males without dementia, indicating that testosterone may have beneficial effects on brain function.

Objective: To investigate whether APOE ε4 affects the association of verbal memory with neurodegeneration presented by the hippocampal volume/intracranial volume ratio (HpVR).Methods: The study sample included 371 individuals with normal cognition (NC), 725 subjects with amnestic mild cognitive impairment (aMCI), and 251 patients with mild Alzheimer’s disease (AD) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) who underwent the rey auditory verbal learning test (RAVLT). Multiple linear regression models were conducted to assess the effect of the APOE ε4∗HpVR interaction on RAVLT in all subjects and in each diagnostic group adjusting for age, gender and educational attainment, and global cognition.Results: In all subjects, there was no significant APOE ε4 × HpVR interaction for immediate recall or delayed recall (p > 0.05). However, in aMCI subjects, there was a significant APOE ε4 × HpVR interaction for delayed recall (p = 0.008), but not immediate recall (p = 0.15). More specifically, the detrimental effect of APOE ε4 on delayed recall altered by HpVR such that this effect was most evident among subjects with small to moderate HpVR, but this disadvantage was absent or even reversed among subjects with larger HpVR. No significant interaction was observed in the NC or AD group.Conclusion: These findings highlight a potential role of APOE ε4 status in affecting the association of hippocampus size with delayed recall memory in the early stage of AD.

GaN nucleation layers were grown on sapphire substrate by metal organic chemical vapor deposition (MOCVD) with different carrier gas. The morphology of nucleation layer which is crucial to GaN crystal quality was systematically studied using nitrogen and hydrogen as carrier gas. The GaN nucleation layer tends to form larger islands under H2 ambient, and forms higher density nucleation islands and thicker nucleation layer under N2 ambient.

The wide range of pressure detection and the exceptional linearity are essential performance parameters for flexible pressure sensors, enabling them to adapt to diverse scenarios and acquire information accurately. However, currently available "ultra‐wide range" piezoresistive sensors lack an optimal solution that effectively balances sensing properties, device thickness, and process cost. This study proposes a distinctive approach by introducing a Janus conductive structure assembled with dual resistive sensitive layers. The design allows for a pressure‐induced staged transformation of the current transport path, effectively mitigating variations and saturation in sensor resistance over a wide pressure range. The resulting piezoresistive sensor demonstrates an unprecedented detection range of 0–3800 kPa, showcasing remarkable sensitivity of 4.11 kPa−1 and outstanding linearity of 99.9% within the range of 0–1000 kPa. Additionally, the sensor boasts a thickness of only ≈200 µm, made possible through the utilization of a cellulose nanofibers material matrix. These performance achievements stand at the forefront when compared to existing reports. This research explores the potential applications of these sensors and extended arrays in the domains of human health and motion monitoring. It investigates their utility in gait analysis for assisted posture correction, as well as in the assessment and rehabilitation of gait instability. [ABSTRACT FROM AUTHOR]

Berberine (BBR), as a natural isoquinoline alkaloid, has demonstrated various pharmacological activities, and is widely applied in the treatment of diseases. The quantitative analysis of BBR is important for pharmacological studies and clinical applications. In this work, utilizing the specific interaction between BBR and triplex DNA, a sensitive and selective fluorescent detecting method was established with DNA-templated silver nanoclusters (DNA-AgNCs). After binding with the triplex structure in the template of DNA-AgNCs, BBR quenched the fluorescence of DNA-AgNCs and formed BBR-triplex complex with yellow–green fluorescence. The ratiometric fluorescence signal showed a linear relationship with BBR concentration in a range from 10 nM to 1000 nM, with a detection limit of 10 nM. Our method exhibited excellent sensitivity and selectivity, and was further applied in BBR detection in real samples. [ABSTRACT FROM AUTHOR]

This article aims to improve the inefficiency of the sports service supply chain (SC) caused by the unscientific management of stakeholders in the sports service SC. First, combined with the literature, the identification and management of the service SC domestically and internationally are explained, providing a meaningful reference for improving sports service bases. Second, fuzzy comprehensive appraisal (FCA) algorithm process and artificial intelligence (AI) technology are used to evaluate and manage the risk of sports service SC. The FCA algorithm provides a comprehensive evaluation factor set for the sports service SC risk evaluation. Then, the complete evaluation set is established. To obtain the evaluation matrix, the 'expert' carries out fuzzy evaluation on each single factor. AI provides a data analysis platform for integrated SC risk management. The platform can realize the logical hierarchical relationship between indicators and rules, systematically standardize the sports service SC and rules, and conduct unified display, monitoring, and trend analysis. Finally, the FCA method is used to evaluate the risks of the sports service SC, and the results of the comprehensive management of the dangers of the SC are analysed. The results show that the evaluation indicators of sports service venues' SC service capabilities have a good consistency. The highest weight score of government service capability in the sports service SC is 0.2413, and the lowest weight score of the service capability index of the sports operation platform is 0.1708. Sports service venues' SC capacity in NANCHANG City is relatively average. This article deeply understands the structure of the sports service SC. It provides relevant basis and guidance for sports service integrators, service providers, and other market entities to adjust management strategies and improve market competitiveness. It also clarifies the risks and management results of the sports service SC, provides academic help for the researchers and enriches and develops the theory of the reform and construction of the Chinese sports service SC. [ABSTRACT FROM AUTHOR]

The repeat expansions are the main genetic cause of various neurodegeneration diseases. More than ten kinds of repeat sequences with different lengths, locations, and structures have been confirmed in the past two decades. G-rich repeat sequences, such as CGG and GGGGCC, are reported to form functional G-quadruplexes, participating in many important bioprocesses. In this review, we conducted an overview concerning the contribution of G-quadruplex in repeat expansion disorders and summarized related mechanisms in current pathological studies, including the increasing genetic instabilities in replication and transcription, the toxic RNA foci formed in neurons, and the loss/gain function of proteins and peptides. Furthermore, novel strategies targeting G-quadruplex repeats were developed based on the understanding of disease mechanism. Small molecules and proteins binding to G-quadruplex in repeat expansions were investigated to protect neurons from dysfunction and delay the progression of neurodegeneration. In addition, the effects of environment on the stability of G-quadruplex were discussed, which might be critical factors in the pathological study of repeat expansion disorders. [ABSTRACT FROM AUTHOR]

Abstract The trinucleotide repeat d(CXG) (X = A, C, G or T) is the most common sequence causing repeat expansion disorders. The formation of non-canonical structures, such as hairpin structures with X-X mismatches, has been proposed to affect gene expression and regulation, which are important in pathological studies of these devastating neurological diseases. However, little information is available regarding the thermodynamics of the repeat sequence under crowded cellular conditions where many non-canonical structures such as G-quadruplexes are highly stabilized, while duplexes are destabilised. In this study, we investigated the different stabilities of X-X mismatches in the context of internal d(CXG) self-complementary sequences in an environment with a high concentration of cosolutes to mimic the crowding conditions in cells. The stabilities of full-matched duplexes and duplexes with A-A, G-G, and T-T mismatched base pairs under molecular crowding conditions were notably decreased compared to under dilute conditions. However, the stability of the DNA duplex with a C-C mismatch base pair was only slightly destabilised. Investigating different stabilities of X-X mismatches in d(CXG) sequences is important for improving our understanding of the formation and transition of multiple non-canonical structures in trinucleotide repeat diseases, and may provide insights for pathological studies and drug development. Highlights • The stabilities of X-X mismatches were T-T ≥ G-G > A-A ≥ C-C under crowding conditions. • The stability of C-C mismatch was less affected by crowding conditions. • Our study might improve our understanding of trinucleotide repeat diseases. [ABSTRACT FROM AUTHOR]

For the first time, a novel type of chameleon DNA-templated silver nanocluster (AgNC) is found whose fluorescence color can be switched among yellow, orange, and red by the regulation of complementary DNA, nonfluorescent assistant AgNC as well as Mg2+. AgNC templated by A20-C55 (A20-C55-NC) possesses strong yellow fluorescence (Y signal) in phosphate buffer solution. When approaching to the nonfluorescent assistant AgNC through template hybridization, Y signal decreases while a new red emission (R signal) rises, leading to a dramatic color change of AgNC solution from yellow to red. On the other hand, hybridization of A20-C55-NC with complementary DNA (T20) largely enhances the Y signal while A20-C55-NC shows R and Y signal with equal intensity simultaneously in the presence of Mg2+. Therefore, the chameleon AgNC achieves controllable multicolor fluorescence variation. Based on above mechanism, a series of ratiometric analysis platforms are constructed for DNA target detection. Surprisingly, the ratiometric probes demonstrate an exponential growth of signal response with nanomolar sensitivity whether in double-stranded or hairpin-shaped structure. Accordingly, this universal ratiometric analysis platform possesses low background, large signal variation in a narrow concentration range, which presents obvious advantages over most of previous DNA detection strategies that are based on DNA-templated AgNC. [ABSTRACT FROM AUTHOR]

Mutual transformation between α2 and ωo phases has been an interesting topic in recent years. In this study, martensitic α2 was obtained by air-cooling from 1250 °C in Ti-37.5Al-12.5Nb (at%) alloy while four ωovariants formed in the βo phase matrix during the cooling process. Nonetheless, only one ωo variant was observed at the periphery of the α2 plates in the βo phase and the orientation relationship between these two phases was [0001] α2//[1210 ] ωo; (1120) α2//(0002) ωo. Thin γ plates precipitated within the α2 phase and were thought to be related to the appearance of ωo phase. The redistribution of the compositions during the phase transformations was studied by energy dispersive X-ray spectroscopy analysis. The corresponding mechanisms of the phase transformations mentioned above are discussed. [ABSTRACT FROM AUTHOR]

In this work, we developed a novel light-up nanocluster beacon (NCB) based on shuttling dark silver nanoclusters (NCs) to a bright scaffold through hybridization. The fluorescence enhancement was as high as 70-fold when the two templates were on the opposite sides of the duplexes, enabling sensitive and selective detection of DNA. [ABSTRACT FROM AUTHOR]

In this paper, we developed a simple, low-cost and sensitive DNA sequences detection biosensor based on a label-free molecular beacon (MB) whose DNA hairpin structure terminal has a guanine-rich sequence that can enhance fluorescence of silver nanoclusters (Ag NCs). Without hybridization between hairpin probe and target DNA, the Ag NCs presented bright fluorescence for the proximity of guanine-rich sequences (GRSs). After binding with target DNA, the hairpin shape was destroyed which results in a decrease of the Ag NCs fluorescence intensity. With this biosensor, we detected three disease-related genes that were the human immunodeficiency virus (HIV) gene, hepatitis B virus (HBV) gene and human T-lymphotropic virus type I (HTLV-I) gene. The detection limits based on S/N of 3 were 4.4 nM, 6.8 nM and 8.5 nM for HIV gene, HBV gene and HTLV-I gene, respectively. Our sensor was also of high selectivity and could distinguish even one nucleotide mismatched target. [ABSTRACT FROM AUTHOR]

Background: There is no existing report on the quality of randomized controlled trials (RCTs) of melasma treatment currently conducted in China. This study aims to assess the quality of RCT- reporting in the treatment of melasma conducted in China. Methods: Several databases were searched from their inception through to August 2014. In order to rate the report quality, we scored 1 for the item if it was reported in CONSORT 2010 and 0 for the item if it was not definitely stated or was not clear. For overall quality score (OQS), 13 items were scored and calculated with a range of 0 to 13. Five items ('randomization', 'allocation concealment', 'blinding', 'baseline characteristics' and 'intention-to-treat (ITT) analysis') were scored and a key methodological index score (MIS) was calculated with a range of 0 to 5 for each trial. Results: A total of 246 relevant RCTs were included in the final analysis. The median OQS was 7, with a minimum of 4 and a maximum of 11. Some items' information was insufficient, especially in the categories of 'trial design', 'sample size', 'recruitment' and 'ancillary analyses' with a positive rate of less than 20%. The median MIS was 1 with a minimum of 0 and a maximum of 3. Some items' reporting was poor, especially in the categories of 'randomization', 'allocation concealment and implementation', 'blinding' and 'ITT analysis' with a positive rate of less than 10%. The mean OQS increased by about 0.52 for manuscripts published in the period of 5-year increments (95% CI: 0.32 to 0.72; P < 0.001). With regard to the MIS, no variable was statistically significant in the ordinal regression model. Conclusion: The reporting quality of RCTs in the treatment of melasma conducted in China is not satisfactory especially in key methodological items. Reporting of RCTs in this field should meet and keep up with the standards of the CONSORT statement. [ABSTRACT FROM AUTHOR]

Analyse the gas-solid separation efficiency and its influencing factors of coal gas in the technology of partially gasified coal gas reburn to reduce NOx. Build a gas-solid separation cold test rig of coal gas, which matches with a 130 tons cold hearth, exam the impact of separator wind and carrier gas flow rate on gas-solid separation effect of material in the separation device. The results show that, when the intake flow rate of the bottom inlet v1 is 10 m/s, and the flow velocity of the top inlet v2 is 5 m/s, the separation efficiency of semi-coke is the highest, and the separation efficiency of volatile also achieves greater value, the volatile can be well separated from semi-coke. [ABSTRACT FROM AUTHOR]

A novel approach was developed to study the relationship between DNA sequences and DNA-templated silver nanoclusters (DNA-Ag NCs) in detail by using an ordinary DNA strand as an example. Three kinds of Ag NCs are formed by using the DNA strand as a scaffold. By dividing the DNA template into several parts according to their different affinities to Ag+, it was found that the fluorescence properties of DNA-Ag NCs are related to not only the sequences but also to the position of different parts in the template, which provides a more efficient approach to obtain DNA-Ag NCs with required photoluminescence properties and may ultimately contribute to the targeted synthesis of DNA-Ag NCs. [ABSTRACT FROM AUTHOR]

Ginsenoside compound K (CK) is one of the major metabolites of the bioactive ingredients in Panax ginseng, which presents excellent bioactivity and regulates the expression of important proteins. In this work, the effects of CK on G-quadruplexes (G4s) were quantitatively analyzed in the presence and absence of their complementary sequences. CK was demonstrated to facilitate the formation of G4s, and increase the quantity of G4s in the competition with duplex. Thermodynamic experiments suggested that the electrostatic interactions were important for G4 stabilization by CK. CK was further found to regulate the transcription of G4-containing templates, reduce full-length transcripts, and decrease the transcription efficiency. Our results provide new evidence for the pharmacological study of ginsenosides at the gene level. [ABSTRACT FROM AUTHOR]

The properties of non-canonical DNA structures, like G-quadruplexes and triplexes, change under cell-mimicking molecular crowding conditions relative to dilute aqueous solutions. The analysis of environmental effects on their stability is crucial since they play important roles in gene expression and regulation. In this study, three intramolecular and intermolecular triplex-forming sequences of different C+*G-C triplet content (*: Hoogsteen base pair; - : Watson–Crick base pair) were designed and their stability measured in the absence and presence of a crowding agent with different K+ concentrations. In dilute solution, the stability of the triplexes was reduced by decreasing the concentration of KCl. This reduction became smaller as the number of C+*G-C triplets increased. Under molecular crowding conditions, Watson–Crick base pairs and Hoogsteen base pairs were destabilized and stabilized, respectively. Interestingly, with lower KCl concentrations (≤1 M), the destabilization of the triplexes due to reduction of KCl concentration was significantly smaller than in dilute solutions. In addition, the C+*G-C content had greater influence on triplex stability under molecular crowding conditions. Our work provides quantitative information about the effects of K+ concentration on triplex stability under molecular crowding conditions and should further our understanding of the function and regulation of triplexes in bioprocesses. [ABSTRACT FROM AUTHOR]

Nucleic acid stability and structure, which are crucial to the properties of fluorescent DNA-templated silver nanoclusters (DNA-Ag NCs), significantly change in ionic liquids. In this work, our purpose was to study DNA-Ag NCs in a buffer containing the hydrated ionic liquid of choline dihydrogen phosphate (choline dhp) to improve fluorescence for application in DNA detection. Due to the stabilisation of an i-motif structure by the choline cation, a unique fluorescence emission—that was not seen in an aqueous buffer—was observed in choline dhp and remained stable for more than 30 days. A DNA-Ag NCs probe was designed to have greater fluorescence intensity in choline dhp in the presence of a target DNA. A turn-on sensing platform in choline dhp was built for the detection of the BRCA1 gene, which is related to familial breast and ovarian cancers. This platform showed better sensitivity and selectivity in distinguishing a target sequence from a mutant sequence in choline dhp than in the aqueous buffer. Our study provides new evidence regarding the effects of structure on properties of fluorescent DNA-Ag NCs and expands the applications of fluorescent DNA-Ag NCs in an ionic liquid because of improved sensitivity and selectivity. [ABSTRACT FROM AUTHOR]

Objective To investigate the application of Legiolert enzyme-substrate method with mass spectrometry in direct quantitative detection and separation of Legionella pneumophila in environmental water samples. Methods Collection of 14 public places in Nanjing from July 2021 to November 2021, including hotels and restaurants, leisure centers and other centralized air conditioning cooling water 18, shower water 30 and other total 48 samples. Legiolert enzyme-substrate method was used to detect Legionella pneumophila in water samples, and the isolated cultured pure colonies were identified for serological typing with mass spectrometry and fluorescence quantitative PCR test. The detection rate of Legionella pneumophila was compared with that by traditional isolated and cultured method. Results The detection rates of Legionella pneumophila in 48 samples were 8.33% (4/48) by traditional method and 31.25% (15/48) by mass spectrometry and fluorescence quantitative PCR. There was a significantly difference in it between two detection methods (χ2＝5.37, P

Background Hypodermin A (HA) is a serine esterase that degrades complement, a key element of the innate immune system. Immunosuppressive properties of HA have previously been studied in vitro . However, such properties have not been fully demonstrated in vivo . The aim of this study was to evaluate the effect of HA in inhibiting allograft rejection in an HA transgenic mouse model. Methods FVB (HA transgenic mice or wild-type mice) to BALB/c mice skin transplantation model were used. Skin grafts were analyzed by histology, immunohistochemistry, and Western blotting. Results HA overexpression resulted in significantly prolonged skin allograft survival. Histologic changes in the skin allografts paralleled the gross appearance of rejection. ELISA and Western blotting showed that HA significantly reduced the content of complement C3 and C9 in HA skin allografts. The expressions of CD4, B7-2, and MHC class II were all significantly suppressed in HA skin allografts compared with the control group. Conclusions These findings suggest that HA effectively prolongs skin allograft survival. The study results provide insight into a promising strategy to improve the survival of grafts in humans. [ABSTRACT FROM AUTHOR]

Abstract: Hypodermin A (HA), a serine protease secreted by first-instar larvae of Hypoderma lineatum (Diptera: Oestridae) is associated with inflammatory and the specific immune responses in cattle hosts. In the present study, the cDNA sequence of HA was synthesized, and found to have fifteen amino acids which differed from the sequence available in GenBank. We then examined the association between recombinant HA and guinea-pig complement component 3 (C3) through a co-immunoprecipitation assay. Cos7 cells stably expressing HA were generated, and were found to be more resistant to lysis by guinea-pig C3 than the controls. HA was also able to degrade the C6 and C5b-9 of guinea-pig C3. The presumed DNA binding site of HA with guinea-pig C3 was detected by an electrophoretic mobility shift assay (EMSA). In contrast, after stable transfection, mHA was unable to reduce the amount of C3 or to inhibit its cytotoxicity, while HA could degrade guinea-pig C3 and inhibit the complement pathway. The findings suggest that recombinant HA could serve as an immunosuppressive agent against organ rejection after xenotransplantation. [Copyright &y& Elsevier]

Background: Trimethylamine-N-oxide (TMAO) is produced by hepatic flavin-containing monooxygenase 3 (FMO3) from trimethylamine (TMA). High TMAO level is a biomarker of cardiovascular diseases and metabolic disorders, and it also affects periodontitis through interactions with the gastrointestinal microbiome. While recent findings indicate that periodontitis may alter systemic TMAO levels, the specific mechanisms linking these changes and particular oral pathogens require further clarification., Methods: In this study, we established a C57BL/6J male mouse model by orally administering Porphyromonas gingivalis ( P. gingivalis , Pg ), Fusobacterium nucleatum ( F. nucleatum , Fn ), Streptococcus mutans ( S. mutans , Sm ) and PBS was used as a control. We conducted LC-MS/MS analysis to quantify the concentrations of TMAO and its precursors in the plasma and cecal contents of mice. The diversity and composition of the gut microbiome were analyzed using 16S rRNA sequencing. TMAO-related lipid metabolism and enzymes in the intestines and liver were assessed by qPCR and ELISA methods. We further explored the effect of Pg on FMO3 expression and lipid molecules in HepG2 cells by stimulating the cells with Pg -LPS in vitro ., Results: The three oral pathogenic bacteria were orally administered to the mice for 5 weeks. The Pg group showed a marked increase in plasma TMAO, betaine, and creatinine levels, whereas no significant differences were observed in the gut TMAO level among the four groups. Further analysis showed similar diversity and composition in the gut microbiomes of both the Pg and Fn groups, which were different from the Sm and control groups. The profiles of TMA-TMAO pathway-related genera and gut enzymes were not significantly different among all groups. The Pg group showed significantly higher liver FMO3 levels and elevated lipid factors (IL-6, TG, TC, and NEFA) in contrast to the other groups. In vitro experiments confirmed that stimulation of HepG2 cells with Pg -LPS upregulated the expression of FMO3 and increased the lipid factors TC, TG, and IL-6., Conclusion: This study conclusively demonstrates that Pg , compared to Fn and Sm , plays a critical role in elevating plasma TMAO levels and significantly influences the TMA-TMAO pathway, primarily by modulating the expression of hepatic FMO3 and directly impacting hepatic lipid metabolism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Chen, Teng, Xie, Huang, Wu, Wang and Xie.)

The morphology and function of the cerebellum are associated with various developmental disorders and healthy aging. Changes in cerebellar morphology during the aging process have been extensively investigated, with most studies focusing on changes in cerebellar regional volume. The volumetric method has been used to quantitatively demonstrate the decrease in the cerebellar volume with age, but it has certain limitations in visually presenting the morphological changes of cerebellar atrophy from a three-dimensional perspective. Thus, we comprehensively described cerebellar morphological changes during aging through volume measurements of subregions and shape analysis. This study included 553 healthy participants aged 20-80 years. A novel cerebellar localized segmentation algorithm based on convolutional neural networks was utilized to analyze the volume of subregions, followed by shape analysis for localized atrophy assessment based on the cerebellar thickness. The results indicated that out of the 28 subregions in the absolute volume of the cerebellum, 15 exhibited significant aging trends, and 16 exhibited significant sex differences. Regarding the analysis of relative volume, only 11 out of the 28 subregions of the cerebellum exhibited significant aging trends, and 4 exhibited significant sex differences. The results of the shape analysis revealed region-specific atrophy of the cerebellum with increasing age. Regions displaying more significant atrophy were predominantly located in the vermis, the lateral portions of bilateral cerebellar hemispheres, lobules I-III, and the medial portions of the posterior lobe. This atrophy differed between sexes. Men exhibited slightly more severe atrophy than women in most of the cerebellar regions. Our study provides a comprehensive perspective for observing cerebellar atrophy during the aging process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Teng, Liu, Tang, Liang, Wang, Li, Xia, Xu and Liu.)

Background: Among older adults, type 2 diabetes mellitus (T2DM) is widely recognized as one of the most prevalent diseases. Diabetic nephropathy (DN) is a frequent complication of DM, mainly characterized by renal microvascular damage. Early detection, aggressive prevention, and cure of DN are key to improving prognosis. Establishing a diagnostic and predictive model for DN is crucial in auxiliary diagnosis., Aim: To investigate the factors that impact T2DM complicated with DN and utilize this information to develop a predictive model., Methods: The clinical data of 210 patients diagnosed with T2DM and admitted to the First People's Hospital of Wenling between August 2019 and August 2022 were retrospectively analyzed. According to whether the patients had DN, they were divided into the DN group (complicated with DN) and the non-DN group (without DN). Multivariate logistic regression analysis was used to explore factors affecting DN in patients with T2DM. The data were randomly split into a training set ( n = 147) and a test set ( n = 63) in a 7:3 ratio using a random function. The training set was used to construct the nomogram, decision tree, and random forest models, and the test set was used to evaluate the prediction performance of the model by comparing the sensitivity, specificity, accuracy, recall, precision, and area under the receiver operating characteristic curve., Results: Among the 210 patients with T2DM, 74 (35.34%) had DN. The validation dataset showed that the accuracies of the nomogram, decision tree, and random forest models in predicting DN in patients with T2DM were 0.746, 0.714, and 0.730, respectively. The sensitivities were 0.710, 0.710, and 0.806, respectively; the specificities were 0.844, 0.875, and 0.844, respectively; the area under the receiver operating characteristic curve (AUC) of the patients were 0.811, 0.735, and 0.850, respectively. The Delong test results revealed that the AUC values of the decision tree model were lower than those of the random forest and nomogram models ( P < 0.05), whereas the difference in AUC values of the random forest and column-line graph models was not statistically significant ( P > 0.05)., Conclusion: Among the three prediction models, random forest performs best and can help identify patients with T2DM at high risk of DN., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)