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Fixed-wing unmanned aerial vehicles (UAVs) are widely considered as a vital candidate of aerial base station in beyond Fifth Generation (B5G) systems. Accurate knowledge of air-to-ground (A2G) wireless propagation is important for A2G communication system development and testing where, however, there is still a lack of A2G wideband channel models for such a purpose. In this paper, we present a wideband fixed-wing UAV-based A2G channel measurement campaign at 2.7 GHz, and consider typical flight phases, based on which a wide-sense stationary uncorrelated scattering (WSSUS)-based tapped delay line (TDL) wideband channel model is proposed. Parameters of individual channel taps are analyzed in terms of gain, amplitude distribution, Rice factor and delay-Doppler spectrum. It is shown that UAV flight phases significantly influence the channel tap parameters. Particularly, the “Bell”-type spectrum is found to be the most suitable model for the delay-Doppler spectrum under various flight scenarios for A2G propagation. The proposed channel model can provide valuable assistance and guidance for UAV communication system evaluation and network planning.

The wettability and stability of a solution’s film on the filler surface are the key factors determining heat and mass transfer efficiency in liquid desiccant air conditioning systems. Therefore, this study investigates the effects of different air parameters on the flow behavior of a lithium chloride solution’s film. The effects of air velocity, air flow pattern, and pressure on the wettability and critical amount of spray are discussed. The results show that the main mechanism by which the air velocity affects the wettability is that the shear stress generated by the direction of the air velocity disperses the direction of the surface tension and weakens its effect on the liquid film distribution. In addition, in the counter flow pattern, the air flow blocks the liquid film from spreading longitudinally and destroys the stability of the liquid film at the liquid outlet, which increases the critical amount of spray. The pressure distribution is similar under different operating pressures when the flow is stable; thus, pressure has little effect on wettability. The simulation results under 8 atm are compared with the experimental results. It is found that the sudden increase in the amount of moisture removal when the amount of spray changes from 0.05 to 0.1 m3/(m·h) in the experiment is caused by the change in the liquid film flow state. In addition, the results show that within the range of air flow parameters for the liquid desiccant air conditioning system, air flow shear force is not the main factor affecting the stability of the solution’s film, and there is no secondary breakage of the solution’s film during the falling-film flow process.

Background: Artificial Light at Night (ALAN) is an emerging health risk factor that has been linked to a wide range of adverse health effects. Recent study suggested that disadvantaged neighborhoods may be exposed to higher levels of ALAN. Understanding how social disadvantage correlates with ALAN levels is essential for identifying the vulnerable populations and for informing lighting policy. Methods: We used satellite data from the National Aeronautics and Space Administration’s (NASA) Black Marble data product to quantify annual ALAN levels (2012–2019), and the Center for Disease Control and Prevention’s (CDC) Social Vulnerability Index (SVI) to quantify social disadvantage, both at the US census tract level. We examined the relationship between the ALAN and SVI (overall and domain-specific) in over 70,000 tracts in the Contiguous U.S., and investigated the heterogeneities in this relationship by the rural-urban status and US regions (i.e., Northeast, Midwest, South, West). Results: We found a significant positive relationship between SVI and ALAN levels. On average, the ALAN level in the top 20% most vulnerable communities was 2.46-fold higher than that in the 20% least vulnerable communities (beta coefficient (95% confidence interval) for log-transformed ALAN, 0.90 (0.88, 0.92)). Of the four SVI domains, minority and language status emerged as strong predictors of ALAN levels. Our stratified analysis showed considerable and complex heterogeneities across different rural-urban categories, with the association between greater vulnerability and higher ALAN primarily observed in urban cores and rural areas. We also found regional differences in the association between ALAN and both overall SVI and SVI domains. Conclusions: Our study suggested ALAN as an environmental justice issue that may carry important public health implications.FundingNational Aeronautics and Space Administration.

As a low-carbon cementitious material, the application of fly ash based geopolymer in ground improvement has attracted more and more attention. However, the engineering characteristics of the soil stabilized by alkali activated cementitious material under the freezing-thawing extreme climate conditions are not clear. It is necessary to further study the strength, deformation characteristics and their influencing factors of the improved soil under the freezing-thawing cycle. Several laboratory tests are carried out to investigate the effects of the ratio of silicon to aluminum in raw material (Si/Al), modulus of alkali-activator and alkali solution concentration on the unconfined compressive strength (UCS) and the freezing-thawing resistance of fly ash based geopolymer stabilized soil, and the corresponding micro mechanism. The results show that (1) the UCS of geopolymer stabilized soil decreases with the increasing alkali-activator modulus and the decreasing alkali solution concentration, while increases with the Si/Al value in the range of 1.15 to 1.35, and the unconfined compressive strength of 28 d geopolymer stabilized soil can reach 8.98 MPa. (2) When the Si/Al value changes from 1.25 to 1.35 and the alkali solution concentration is within the range of 5.42 to 22.78 mol/L, the 28 d geopolymer stabilized soil can resist more than one (up to 6) freezing-thawing cycle. (3) The best performance of the freezing-thawing resistance of fly ash based geopolymer stabilized soil is mainly related to large number of Si-rich aluminosilicate gel generated by polymerization, while the highest compressive strength is related to the amount of Al-rich aluminosilicate gel generated by polymerization. The research results will provide technical reference for the mix design of soil stabilization with fly ash based geopolymer, and promote the application of alkali activated cementitious material in ground improvement.

Abstract Background Lack of biomarkers and in vitro models has contributed to inadequate understanding of the mechanisms underlying the inferior clinical response to immune checkpoint inhibitors (ICIs) in patients with oncogene-driven non-small cell lung cancer (NSCLC). Methods The effect of small molecule tyrosine kinase inhibitors (TKIs) on peripheral blood mononuclear cells (PBMCs) in 34 patients with oncogene-driven NSCLC (cohort A) was compared with those from 35 NSCLC patients without oncogene-driven mutations received ICI (cohort B) or from 22 treatment-naïve NSCLC patients (cohort C). Data for each blood biomarker were summarized by mean and standard deviation and compared by Wilcoxon rank sum tests or Kruskal-Wallis tests with significance at 2-sided p value

The flat dilatometer test (DMT) has been widely used in engineering such as geotechnical engineering investigation and evaluation of ground improvement effect at home and abroad. The test process of DMT is usually carried out after the blade insertion of DMT into test position, so the disturbance caused by the dilatometer penetration process will directly affect test results to a certain extent. However, the mechanism of dilatometer penetration and soil disturbance and its influence on test results caused by penetration process are not yet known. Homogeneous dry sand samples under different initial densities are prepared by the layered plate compaction method with low level rainfall, and several laboratory model tests of dilatometer penetration into these sand samples together with particle image velocimetry (PIV) are carried out to investigate the distribution characteristics of the soil displacement field during the blade penetration process. The test results show that (1) the extrusion effect caused by the penetration of both the wedge part and lateral expansion part of the blade mainly causes soil disturbance. (2) The surrounding soil is squeezed downward and sideward during the penetration of the wedge part of blade, resulting in small vertical displacement and a flat displacement field which mainly extends to both sides, while the surrounding soil is squeezed horizontally to the two sides during the penetration of the lateral expansion part of blade, resulting in a semi-elliptical horizontal displacement field with the distribution range being obviously larger, and meanwhile, the shear effect caused by side friction between the blade and soil produce a vertical displacement field with a narrow range. (3) Moreover, the displacement field of dry sand caused by dilatometer blade penetration is less affected by the initial sand density than that by cone probe penetration, and only the distribution range of displacement field around the wedge part of the dilatometer blade expands with the increase of the initial density to some extent.

Low maturity coal samples were taken from the Ordos Basin to conduct gold tube thermal simulation experiment in a closed system, and the characteristics of the products were analyzed to find out the fractionation mechanism of carbon isotopes and the causes of abnormal carbon isotopic compositions of natural gas. At the heating rates of 2 °C/h (slow) and 20 °C/h (rapid), the low maturity coal samples of the Ordos Basin had the maximum yields of alkane gas of 302.74 mL/g and 230.16 mL/g, the δ13C1 ranges of −34.8‰ to −23.6‰ and −35.5‰ to −24.0‰; δ13C2 ranges of −28.0‰ to −9.0‰ and −28.9‰ to −8.3‰; and δ13C3 ranges of −25.8‰ to −14.7‰ and −26.4‰ to −13.2‰, respectively. Alkane gas in the thermal simulation products of rapid temperature rise process showed obvious partial reversal of carbon isotope series at 550°C, and at other temperatures showed positive carbon isotope series. In the two heating processes, the δ13C1 turned lighter first and then heavier, and the non-monotonic variation of the δ13C1 values is because the early CH4 is from different parent materials resulted from heterogeneity of organic matter or the carbon isotope fractionation formed by activation energy difference of early enriched 12CH4 and late enriched 13CH4. The reversal of carbon isotope values of heavy hydrocarbon gas can occur not only in high to over mature shale gas (oil-type gas), but also in coal-derived gas. Through thermal simulation experiment of toluene, it is confirmed that the carbon isotope value of heavy hydrocarbon gas can be reversed and inversed at high to over mature stage. The isotope fractionation effect caused by demethylation and methyl linkage of aromatic hydrocarbons may be an important reason for carbon isotope inversion and reversal of alkane gas at the high to over mature stage.

Purpose Given the unmet need for novel immunotherapy in soft tissue sarcoma (STS), we sought to characterize the phenotype and function of intratumoral natural killer (NK) and T cells to identify novel strategies to augment tumor-infiltrating lymphocyte (TIL) function.Experimental design Using prospectively collected specimens from dogs and humans with sarcomas, archived specimens, and The Cancer Genome Atlas (TCGA) data, we evaluated blood and tumor NK and T cell phenotype and function and correlated those with outcome. We then assessed the effects of interleukin 15 (IL-15) stimulation on both NK and T cell activation and TIGIT upregulation. Finally, we evaluated cytotoxic effects of IL-15 combined with TIGIT blockade using a novel anti-TIGIT antibody.Results TILs were strongly associated with survival outcome in both archived tissue and TCGA, but higher TIL content was also associated with higher TIGIT expression. Compared with blood, intratumoral NK and T cells showed significantly higher expression of both activation and exhaustion markers, in particular TIGIT. Ex vivo stimulation of blood and tumor NK and T cells from patients with STS with IL-15 further increased both activation and exhaustion markers, including TIGIT. Dogs with metastatic osteosarcoma receiving inhaled IL-15 also exhibited upregulation of activation markers and TIGIT. Ex vivo, combined IL-15 and TIGIT blockade using STS blood and tumor specimens significantly increased cytotoxicity against STS targets.Conclusion Intratumoral NK and T cells are prognostic in STS, but their activation is marked by significant upregulation of TIGIT. Our data suggest that combined IL-15 and TIGIT blockade may be a promising clinical strategy in STS.

We study the research status of thermal simulation experiment and put forward three issues worthy of attention and five important development directions. Classification according to thermal simulation system is the most widely used classification scheme. Different thermal simulation experimental systems have their own characteristics, and according to different experimental purpose, a suitable thermal simulation experiment system can be selected according to different experimental purposes. The closed experimental system is more suitable for the thermal simulation experiment of humic source rocks. The online analysis of open system has unique advantages in the study of volatile components. The semi-open system is the most closest to the thermal simulation system of the thermal evolution of the source rocks in the actual geological condition. Three key issues are presented concerning the thermal simulation experiment are presented. The first is the influence of water on the thermal simulation experiment. The second is whether convincing isotope reversal can be presented expect Fischer–Tropsch synthesis. The third is that, in the study of the thermal simulation experiment, the model of hydrocarbon generation must be built in combination with the actual geological background. Five key development directions concerning the thermal simulation experiment are proposed. The first is thermal simulation experimental study on a relatively low temperature and a long time with water participation. The second is experimental research on thermal simulation of unconventional petroleum. The third is a study on the development of pore microcracks in source rocks and the correlation of the interaction of fluid discharge in thermal simulation experiments. The fourth is an experimental study on thermal simulation of carbonate source rock. The fifth is an experimental study of thermal simulation related to abnormal pressure. Keywords: Thermal simulation experiment, Research status, Classification scheme, Development direction

Highly optimistic explanatory style (HOES) and highly pessimistic explanatory style (HPES) are two maladaptive ways to explain the world and may have roots in attachment insecurity. The current study aims to explore the effects of security priming – activating supportive representations of attachment security – on ameliorating these maladaptive explanatory styles. 57 participants with HOES and 57 participants with HPES were randomized into security priming and control conditions. Their scores of overall optimistic attribution were measured before and after priming. Security priming had a moderating effect: The security primed HOES group exhibited lower optimistic attribution, while the security primed HPES group evinced higher scores of optimistic attribution. Furthermore, the security primed HOES group attributed positive outcomes more externally, while the security primed HPES group attributed successful results more internally. The results support the application of security priming interventions on maladaptive explanatory styles. Its potential mechanism and directions for future study are also discussed.

Background & Aims: Crotonylation (Kcr), a newly identified post-translation modification (PTM), has been confirmed to be involved in diverse biological processes and human diseases as well. Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a serious threat to people's health. Augmenter of liver regeneration (ALR) is an important liver regulatory protein, and the insufficiency of ALR expression is reported to accelerate liver steatosis progression to liver fibrosis or even hepatic carcinoma (HCC). However, the connection between dysregulated ALR crotonylation and MASLD pathogenesis remains largely unknown., Methods: Steatotic liver samples from human and western diet (WD)-fed mice were employed for detecting Kcr levels. Mitochondrial function and mitochondria-ER interaction (MAM) relevant to ALR-Kcr modification was evaluated for hepatocyte lipid metabolism both in in-vivo and in-vitro experiments., Results: Global protein crotonylation (Kcr) as well as ALR-Kcr was significantly decreased in liver samples of MASLD patients and WD mice. Histone deacetylase1/2 (HDAC1/2) and lysine acetyltransferase 8 (KAT8) were identified responsible for regulation of ALR-Kcr which takes place at lysine 78 (K78). The decrease of ALR crotonylation, might be related to the imbalance between HADC1/2 and KAT8 expression, inhibited its interaction with MFN2, expanding MAM distance and impairing mitochondrial lipid metabolism, and consequently deteriorating hepatic steatosis., Conclusions: The insufficient of ALR crotonylation might be a crucial mechanism contributing to the pathogenesis of MASLD. Keeping ALR crotonylation level would be beneficial for the prevention and treatment of MASLD., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Nanoplastics (NPs) are emerging water contaminants that threaten human health and ecological security. Developing a method for detecting NPs is significant because of their biological toxicity and mobility. In this study, magnetic solid-phase extraction (MSPE) combined with pyrolysis gas chromatography-mass spectrometry (Py-GC/MS) was used for the pretreatment and qualitative detection of NPs in complex matrices to avoid sample dissolution and eluent usages. The developed methodology can quickly achieve low detection limits in tap and river water, with 0.7283 and 0.6474 µg/L, respectively. To enrich NPs in water, magnetic biochars derived from cornstalks (Fe 3 O 4 /BCs, i.e., Fe 3 O 4 /YMG and Fe 3 O 4 /YMG-ZnCl 2 ) were conveniently fabricated using activation and coprecipitation methods and employed as adsorbents for MSPE. The results indicated that the incorporation of Fe 3 O 4 into BC not only rendered it magnetic but also enhanced the diversity of its surface functional groups and adsorption sites, making it suitable for MSPE. Fe 3 O 4 /YMG-ZnCl 2 demonstrated excellent extraction and enrichment capacity for polystyrene NPs (PSNPs) over various competitive species. Additionally, it exhibited good resistance to pH and anions, and its reaction mechanism was verified using adsorption kinetics and isothermal models. In addition, after extracting PSNPs from tap and river water using Fe 3 O 4 /YMG-ZnCl 2 , they were successfully qualitatively analyzed by Py-GC/MS., (© 2024 Wiley‐VCH GmbH.)

Sepsis-induced myocardial dysfunction presents significant challenges in clinical management and is associated with increased mortality. Anisodamine (654-1/-2) has potentials in alleviating cardiac and endothelial impairments associated with sepsis. Exosomes, small vesicles secreted by cells, carry various bioactive molecules, such as nucleic acids, proteins, and lipids. These vesicles can travel to target cells to influence their function and modulating biological processes. In the context of endothelial-cardiac crosstalk, exosomes derived from endothelial cells can transfer signals that either exacerbate or mitigate myocardial injury, playing a crucial role in the progression of cardiovascular diseases. However, the precise role of endothelial-cardiac crosstalk, particularly through exosomes, in mediating the cardioprotective effects of anisodamine remains unclear. This study evaluated the effects of anisodamine on myocardial and endothelial injuries induced by LPS. Mechanisms were analyzed through network pharmacology, molecular docking, Western blotting, and RT-qPCR. The interaction between endothelial and cardiomyocyte inflammatory responses to anisodamine was assessed using a co-culture assay. Furthermore, both in vivo and in vitro assays were conducted to evaluate the effects of anisodamine-/LPS- treated HUVECs exosomes on A16 cell and myocardial function in mice. Anisodamine effectively mitigated apoptosis, inflammation, mitochondrial and myocardial injury, glycocalyx degradation, and oxidative stress by regulating the PI3K-AKT, NLRP-3/Caspase-1/ASC, TNF-α/PKCα/eNOs/NO, and NF-κB/iNOs/NO pathways in A16 cells and HUVECs. Moreover, in vivo and in vitro assays confirmed the protective effects of anisodamine against myocardial injuries mediated by exosomes derived from LPS-treated HUVECs. In summary, anisodamine ameliorated inflammation-induced endothelial and cardiomyocyte dysfunction. The in vitro and in vivo assays demonstrated that anisodamine could alleviate myocardial dysfunction through exosome-mediated mechanisms, offering new therapeutic avenues for treating myocardial injury and highlighting the potential of targeted exosome therapy in clinical settings., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Tumor recurrence and metastasis are important factors affecting postoperative survival in hepatocellular carcinoma (HCC) patients. ADP Ribosylation factor-like GTPase 8B (ARL8B) plays a crucial role in many biological processes, including lysosomal function, immune response, and cellular communication, all of which are related to the occurrence and development of tumors. However, its role in HCC remains unclear. Herein, we revealed that ARL8B is consistently elevated in HCC tissues compared to normal liver tissues, suggesting an unfavorable outcome in HCC patients. Increased ARL8B levels promoted the malignant phenotype of HCC in vitro and in vivo. Notably, ARL8B also induced epithelial-to-mesenchymal transition (EMT) in HCC cells. Mechanistically, the results of bioinformatics analysis combined with mass spectrometry revealed the potential downstream target molecule RAB2A of ARL8B. ARL8B directly interacted with RAB2A and increased the levels of GTP-bound RAB2A, thereby contributing to the activation of the extracellular signal-regulated kinase (ERK) signaling pathway. Interestingly, knockout of ARL8B in Hep3B cells enhanced the antitumor activity of lenvatinib in vitro and in vivo. Furthermore, AAV-shARL8B enhanced the inhibition of HCC growth through lenvatinib, providing new insights into its mechanism of action in lenvatinib-insensitive patients. In conclusion, ARL8B promotes the malignant phenotype of HCC and EMT via RAB2A mediated activation of the MAPK/ERK signaling pathway and is expected to be a valuable prognostic indicator and therapeutic target for HCC patients., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Pancreatitis is a common gastrointestinal disorder that causes hospitalization with significant morbidity and mortality. The mechanistic pathophysiology of pancreatitis is complicated, limiting the discovery of pharmacological intervention methods. Here, we show that the administration of ATN-161, an antagonist of Integrin-α5, significantly mitigates the pathological condition of acute pancreatitis induced by caerulein. We find that CK19-positive pancreatic ductal cells align parallel to blood vessels in the pancreas. In the caerulein-induced acute pancreatitis model, the newly emergent CK19-positive cells are highly vascularized, with a significant increase in vascular density and endothelial cell number. Single-cell RNA sequencing analysis shows that ductal and endothelial cells are intimate interacting partners, suggesting the existence of a ductal-endothelial interface in the pancreas. Pancreatitis dramatically reduces the crosstalk in the ductal-endothelial interface but promotes the Spp-1/Integrin-α5 signaling. Blocking this signaling with ATN-161 significantly reduces acinar-to-ductal metaplasia, pathological angiogenesis, and restores other abnormal defects induced by caerulein. Our work reveals the therapeutic potential of ATN-161 as an uncharacterized pharmacological method to alleviate the symptoms of pancreatitis., Competing Interests: Conflict of interest The authors declare that no conflict of interest exists., (Copyright © 2024 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.)

Plants mount induced resistance and adult plant resistance against different pathogens during the whole growth period. Rice production faces threats from multiple major diseases, including rice blast, sheath blight, and bacterial leaf blight. Here we report that a microRNA module, miR172a-SNB-MYB30, regulates induced resistance and adult plant resistance to these three major diseases via lignification in rice. Mechanistically, pathogens induce expression of miR172a, which down-regulates transcription factor SNB to release its suppression on MYB30, leading to an increase in lignin biosynthesis and disease resistance during the whole growth period. Moreover, expression levels of miR172a and MYB30 are gradually increased and consistently correlated with lignin contents and disease resistance during rice development reaching a peak at full maturity stage, whereas SNB RNA levels are reversely correlated with lignin contents and disease resistance, indicating the involvement of the miR172a-SNB-MYB30 module in plant adult resistance. A high conservation exists in the functional domain of SNB protein and its binding sites in the MYB30 promoter among over 4000 rice accessions; moreover, abnormal expression of miR172a, SNB, or MYB30 compromises yield traits, suggesting an artificial selection of the miR172a-SNB-MYB30 module during rice domestication. Our results reveal a novel role for a conserved miRNA-regulated module that significantly contributes to induced and adult resistance against multiple pathogens via lignin accumulation, advancing our understanding in broad-spectrum resistance and adult resistance., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Background: Healthcare workers (HCWs) can face situations that conflict with their moral beliefs, leading to moral injury, an adverse psychological consequence that was more frequent during the COVID-19 pandemic. Self-compassion is a potential coping mechanism for moral injury by encouraging acceptance of human limitations and suffering., Objectives: This study aimed to examine the associations between self-compassion components and moral injury prevalence among HCWs in Quebec, Canada, during the COVID-19 pandemic., Research Design: A cross-sectional study design was employed. Participants : and research context: The sample of this study consisted of HCWs and leaders from the Quebec province. Participants completed validated self-administered questionnaires assessing both positive and negative self-compassion components (self-kindness vs self-judgment; common humanity vs isolation; and mindfulness vs overidentification) and moral injury dimensions (self-oriented and other-oriented). Prevalence ratios (PRs) and 95% confidence intervals (CIs) for the associations between self-compassion components and moral injury dimensions were modeled using Poison robust regressions. The models were adjusted for various covariates, including sex, age, gender, and socio-demographic and lifestyle factors., Ethical Considerations: Ethical approval for this study was obtained from the ethics committee of the Centre intégré universitaire de santé et de services sociaux de la Capitale-Nationale in Quebec, Canada. All participants provided written informed consent prior to participating in the study. Additionally, permission was sought and obtained from the original authors of the tools used in this study, including the self-compassion and moral injury scales., Results: The study involved 572 HCWs (60.5% nurses) and leaders. Around half of the participants (50.70%) exhibited moderate levels of self-compassion, while the prevalence of low levels of self-compassion ranged from 21.68% to 48.08% for the positive subscales and from 23.78% to 44.41% for the negative subscales. Regarding moral injury, 10.14% of participants reported moderate to high self-oriented moral injury, 29.19% reported moderate to high other-oriented moral injury, and 13.81% demonstrated moderate to high total moral injury. Higher self-compassion levels were associated with lower moral injury prevalence. HCWs with high self-compassion had a 93% lower likelihood of experiencing moral injury (PR: 0.07, 95% CI: 0.03-0.19). Self-kindness demonstrated the strongest association with reduced moral injury (PR: 0.24, 95% CI: 0.11-0.52), followed by mindfulness (PR: 0.37, 95% CI: 0.18-0.75). However, common humanity did not show a statistically significant association with moral injury prevalence., Conclusion: These findings suggest a potential association between self-compassion and reduced prevalence of moral injury among HCWs, highlighting promising interventions to manage moral injury during crises. Such initiatives could promote the mental wellbeing of HCWs and preventing the negative consequences of moral injury, including anxiety, depression, and burnout., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A pot experiment was conducted to investigate the growth response, concentration, and transportation characteristics of Cd and Pb in Sedum aizoon L. in four typical Cd/Pb-contaminated soils from northern and southern China with the addition of different levels of water-soluble chitosan （WSC）. The effect of WSC on physicochemical properties, Cd and Pb forms, and functional groups in contaminated soils was determined to clarify the internal mechanism of WSC promoting Cd and Pb accumulation by S. aizoon . The results showed that WSC improved the physicochemical properties of rhizosphere soil by increasing alkaline nitrogen and organic matter contents and significantly reducing pH values. In addition, WSC significantly increased the acid-extractable Cd and Pb in contaminated soils by 16.3%-34.5% and 88.9%-272.4%, respectively. Fourier transform infrared spectra analysis showed that amino （-NH 2 ） and hydroxyl （-OH） groups in soils were significantly increased by adding WSC. Therefore, the coordination of Cd/Pb with -NH 2 and -OH may play important roles in forming complexes and mobilizing Cd/Pb in soils. Moreover, the improvement in the rhizosphere environment of contaminated soils by WSC contributed to promoting Cd and Pb accumulation by S. aizoon . WSC significantly increased the total Cd and Pb accumulation by 14.5%-72.1% and 55.0%-128.5%, respectively, without obvious growth inhibition. Therefore, it is feasible to apply WSC to promote Cd/Pb accumulation using S. aizoon , while the matching of WSC addition amount, soil pollution condition, and plant materials should be further considered in practical application.

Accurate determination of nanoplastics (NPs) in aquatic ecosystems constitutes a challenge for which highly sensitive analytical methods are necessitated. Herein, a sample pretreatment based on self-made amino-functionalized activated carbon fibers (ACFs-NH 2 ) dispersive solid-phase extraction (DSPE) allows for high-recovery, followed by high-sensitivity detection of NPs by pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). The developed methodology allowed low detection limits (20-100 μg/L) to be achieved quickly in a few steps. Under optimal conditions, ACFs-NH 2 (12.5 mg) was able to recover ≥98.45 % of polystyrene (PS) nanoplastics at high concentration (100 mg/L) in 10 mL seawater. Based on the high adsorption performance of materials, the adsorption dynamics and isotherms were determined to infer the interaction mechanism of PSNPs on ACFs-NH 2 . After adsorption, the target on the surface of the adsorbent can be directly pyrolyzed, which can simplify the operation steps and avoid the elution of organic solvents, making the process more environmentally friendly. This strategy is feasible for the analysis of trace NPs in water systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Platelet-rich plasma (PRP) has been recognized as an effective therapy in regenerative medicine and surgery, which can reduce the risk of antibiotic abuse and promote the healing of infected wounds. Recent advances in PRP-based treatments have focused on the controlled release of growth factors in PRP with biocompatible hydrogels and antimicrobial promotion by introducing hydrogel components or antibiotics, while the inherent antimicrobial activity of PRP is mostly neglected or sacrificed. Here, we demonstrate the combination of an antimicrobial polysaccharide, carboxymethyl chitosan, and PRP to construct an antimicrobial hydrogel via dynamic bonding with oxidized chondroitin sulfate. Significant inhibitory effects against Staphylococcus aureus and Escherichia coli (95 % of inhibition rate) are achieved through the synergistic contributions of the polysaccharide and PRP. Additionally, the resulting hydrogel promotes the migration of NIH-3T3 fibroblasts and collagen deposition by approximately 1.7 and 1.8 times, respectively, thereby accelerating the healing process of infected wounds. This work may bring new perspectives for potent applications of PRP-based hydrogel dressings for antibiotic-free management of infected wounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Resistant infectious diseases caused by gram-negative bacteria are among the most serious worldwide health problems. Antimicrobial peptides (AMPs) have been explored as promising antibacterial, antibiofilm, and anti-infective candidates to address these health challenges., Major Conclusions: Here we report the potent antibacterial effect of the peptide PaDBS1R6 on clinical bacterial isolates and identify an immunomodulatory peptide fragment incorporated within it. PaDBS1R6 was evaluated against Acinetobacter baumannii and Escherichia coli clinical isolates and had minimal inhibitory concentration (MIC) values from 8 to 32 μmol L -1 . It had a rapid bactericidal effect, with eradication showing within 3 min of incubation, depending on the bacterial strain tested. In addition, PaDBS1R6 inhibited biofilm formation for A. baumannii and E. coli and was non-toxic toward healthy mammalian cells. These findings are explained by the preference of PaDBS1R6 for anionic membranes over neutral membranes, as assessed by surface plasmon resonance assays and molecular dynamics simulations. Considering its potent antibacterial activity, PaDBS1R6 was used as a template for sliding-window fr agmentation studies (window size = 10 residues). Among the sliding-window fragments, PaDBS1R6F8, PaDBS1R6F9, and PaDBS1R6F10 were ineffective against any of the bacterial strains tested. Additional biological assays were conducted, including nitric oxide (NO) modulation and wound scratch assays, and the R6F8 peptide fragment was found to be active in modulating NO levels, as well as having strong wound healing properties., General Significance: This study proposes a new concept whereby peptides with different biological properties can be derived by the screening of fragments from within potent AMPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have obvious advantages over MSC therapy. But the strong procoagulant properties of MSC-EVs pose a potential risk of thromboembolism, an issue that remains insufficiently explored. In this study, we systematically investigated the procoagulant activity of large EVs derived from human umbilical cord MSCs (UC-EVs) both in vitro and in vivo. UC-EVs were isolated from cell culture supernatants. Mice were injected with UC-EVs (0.125, 0.25, 0.5, 1, 2, 4 μg/g body weight) in 100 μL PBS via the tail vein. Behavior and mortality were monitored for 30 min after injection. We showed that these UC-EVs activated coagulation in a dose- and tissue factor-dependent manner. UC-EVs-induced coagulation in vitro could be inhibited by addition of tissue factor pathway inhibitor. Notably, intravenous administration of high doses of the UC-EVs (1 μg/g body weight or higher) led to rapid mortality due to multiple thrombus formations in lung tissue, platelets, and fibrinogen depletion, and prolonged prothrombin and activated partial thromboplastin times. Importantly, we demonstrated that pulmonary thromboembolism induced by the UC-EVs could be prevented by either reducing the infusion rate or by pre-injection of heparin, a known anticoagulant. In conclusion, this study elucidates the procoagulant characteristics and mechanisms of large UC-EVs, details the associated coagulation risk during intravenous delivery, sets a safe upper limit for intravenous dose, and offers effective strategies to prevent such mortal risks when high doses of large UC-EVs are needed for optimal therapeutic effects, with implications for the development and application of large UC-EV-based as well as other MSC-EV-based therapies., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objective: Despite the combination of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang (SB-SD) being a recognized Chinese medicinal herbal pair that is commonly used in the treatment of ovarian cancer, there is a poor understanding of their pharmacological mechanisms. This study examines the antitumor properties and potential mechanisms of SB-SD on human ovarian cancer A2780 cells through a multi-omics approach, establishing a pharmacological basis for clinical utilization., Methods: A range of mass ratios and reagents were used in the hot reflux extraction of SB-SD. The inhibitory effect of the SB-SD extracts on A2780 cell proliferation was assessed using the cell-counting kit 8 assay. A zebrafish tumor implantation model was used to evaluate the effects of SB-SD extracts on tumor growth and metastasis in vivo. Transcriptomics and proteomics were used to investigate alterations in biological pathways in A2780 cells after treatment with different concentrations of SB-SD extract. Cell cycle, cell apoptosis, intracellular free iron concentration, intracellular reactive oxygen species (ROS) concentration, malondialdehyde (MDA), and mitochondrial membrane potential were measured. Real-time quantitative reverse transcription polymerase chain reaction and Western blotting were utilized to investigate the effects of heme catabolism and ferritinophagy on ferroptosis induced by SB-SD extract in A2780 cells., Results: The 70% ethanol extract of SB-SD (a mass ratio of 4:1) inhibited A2780 cell proliferation significantly with a half maximal inhibitory concentration of 660 μg/mL in a concentration- and time-dependent manner. Moreover, it effectively suppressed tumor growth and metastasis in a zebrafish tumor implantation model. SB-SD extract induced the accumulation of free iron, ROS, MDA, and mitochondrial damage in A2780 cells. The mechanisms might involve the upregulated expression of ferritinophagy-related genes microtubule-associated protein 1 light chain 3, autophagy-related gene 5, and nuclear receptor coactivator 4., Conclusion: SB-SD extract effectively inhibited the development of ovarian cancer both in vitro and in vivo. Its mechanism of action involved inducing ferroptosis by facilitating heme catabolism and ferritinophagy. This herbal pair holds promise as a potential therapeutic option for ovarian cancer treatment and may be utilized in combination with routine treatment to improve the treatment outcomes of ovarian cancer patients. Please cite this article as: Wang Z, Liu M, Li GX, Zhang L, Ding KY, Li SQ, Gao BQ, Chen P, Choe HC, Xia LY, Yang YT, Liu Y, Sui X, Ma JN, Zhang L. A herbal pair of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang induced ferroptosis in ovarian cancer A2780 cells via inducing heme catabolism and ferritinophagy. J Integr Med. 2024; Epub ahead of print., (Copyright © 2024 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights reserved.)

Aim: To evaluate the efficacy, timing of retreatment and safety of dexamethasone (DEX) implant on macular edema (ME) secondary to diabetic retinopathy (DME) and retinal vein occlusion (RVO-ME) patients who were refractory to anti-vascular endothelial growth factor (VEGF) treatment., Methods: This retrospective study included 37 eyes received at least one DEX implant treatment for DME or RVO-ME between January 1, 2019, and January 1, 2023. These refractory DME and RVO-ME cases received at least 5 anti-VEGF injections and failure to gain more than 5 letters or a significant reduction in central retinal thickness (CRT). The best corrected visual acuity (BCVA) and CRT were measured at baseline, and at 1, 3, 4 and 6mo post-DEX implant injection. Adverse events such as elevated intraocular pressure (IOP) and cataract were recorded., Results: For RVO cases ( n =22), there was a significant increase in BCVA from 0.27±0.19 to 0.35±0.20 at 6mo post-DEX injection ( P <0.05) and CRT decreased from 472.1±90.6 to 240.5±39.0 µm at 6mo ( P <0.0001). DME cases ( n =15) experienced an improvement in BCVA from 0.26±0.15 to 0.43±0.20 at 6mo post-DEX implant injection ( P =0.0098), with CRT reducing from 445.7±55.7 to 271.7±34.1 µm at 6mo ( P <0.0001). Elevated IOP occurred in 45.9% of patients but was well-controlled with topical medications. No cases of cataract or other adverse events were reported., Conclusion: DEX implants effectively improve BCVA and reduce CRT in refractory DME and RVO-ME. Further research with larger cohorts and longer follow-up periods is needed to confirm these findings and assess long-term outcomes., Competing Interests: Conflicts of Interest: Zhong YY, None; Tang C, None; Zhang LY, None; Zhang XD, None; Liu SL, None., (International Journal of Ophthalmology Press.)

Background: Epstein-Barr virus (EBV) infection has been closely linked to the development of various types of cancer. EB nuclear antigen 1 binding protein 2 (EBNA1BP2) is a crucial molecule for stable isolation of EBV in latent infection. However, the role of EBNA1BP2 in multiple tumor types is remains unclear. In this study, we comprehensively analyzed the functional characteristics of EBNA1BP2 and investigate its potential as a prognostic biomarker in pan-cancer., Methods: We utilized data from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) databases and employed various bioinformatics analysis tools, including TIMER2.0, HPA, GEPIA2.0, PrognoScan, cBioPortal, CancerSEA, and BioGRID to explore the expression pattern, prognostic value, immune infiltration, and methylation level of EBNA1BP2 in pan-cancer. Additionally, we conducted enrichment analysis of genes associated with EBNA1BP2 to identify potential biological functions and pathways., Results: Our analysis revealed that EBNA1BP2 expression was significantly higher in tumor tissues compared to tumor-adjacent tissues. We observed that lower expression of EBNA1BP2 in adrenocortical carcinoma (ACC), brain lower grade glioma (LGG), sarcoma (SARC), and uterine carcinosarcoma (UCS) was significantly associated with improved overall survival (OS) and disease-free survival (DFS). Furthermore, the promoter methylation level of EBNA1BP2 was downregulated in the majority of cancer types. At the single-cell level, EBNA1BP2 was found to be positively correlated with cell cycle and DNA repair processes, while negatively correlated with hypoxia. Additionally, EBNA1BP2 was associated with the infiltration of immune cells such as B cells, cancer-associated fibroblast cells, and CD8+ T cells. Gene enrichment analysis indicated that EBNA1BP2 was mainly involved in nucleoplasm and RNA binding pathways., Conclusion: Our findings suggest that EBNA1BP2 may serve as a potential prognostic biomarker for survival in pan-cancer. Further experimental studies are needed to validate these findings and explore the underlying mechanisms by which EBNA1BP2 contributes to tumorigenesis., (© 2024. The Author(s).)

Introduction: To investigate the protective effects of anisodamine (654-1/654-2) against acute kidney injury (AKI) in LPS-induced septic shock rats and explore its molecular mechanisms., Methods: 56 rats were randomly divided into 8 groups: control, LPS, LPS + 654-1, and LPS + 654-2 (1.25, 2.5 and 5 mg/kg). The model was evaluated by monitoring MAP, HR, and plasma LD levels. ELISA and biochemical assay kits were used to measure the levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and kidney injury markers (BUN and CRE). Additionally, RNA-seq and bioinformatic analysis were performed to explore the mechanism of action of 654-1/654-2, and verification was conducted by western blotting and RT-PCR., Results: 654-1/654-2 significantly restored the levels of MAP, HR, and plasma LD in septic shock rats. Furthermore, 654-1/654-2 (5 mg/kg) effectively ameliorated LPS-induced kidney structural damage and exhibited a dose-dependent reduction in levels of inflammatory cytokines and kidney injury markers. In addition, RNA-seq, WB, and RT-PCR analyses revealed that 654-1/654-2 exerted its effects by inhibiting the expressions of the NF-κB and MAPK pathways and activating the Pi3K/Akt/Bcl-2 signaling pathway, thereby mitigating AKI., Discussion: This study suggested that 654-1/654-2 could alleviate AKI in septic shock rats by improving inflammation invasion and cell apoptosis. Notably, 654-1/654-2 collectively suppressed inflammation response through the p38/JNK/AP-1/NF-κB pathway. Additionally, 654-1 promotes survival signaling via the Pi3K/Akt/Bcl-2 pathway, whereas 654-2 reduces apoptosis through the P53/Bax pathway. These findings provided a theoretical basis for the clinical application of 654-1/654-2 in treating organ damage caused by septic shock., Competing Interests: Author FW was employed by Chengdu No. 1 Pharmaceutical Co. Ltd. The remaining 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 Liu, Tang, Zhang, Wan, Xu, Zhang, Zhao, Ao and Peng.)

Exploring the characteristics of vegetation change and its influencing factors is essential to construct an ecological environment. Based on the NDVI dataset from 2000 to 2020, this study analyzed the spatial temporal attributes of NDVI changes in Shandong Province using the Sen trend analysis and the gravity center migration model. Furthermore, the spatial heterogeneity of NDVI and its influencing factors within the whole study area and different soil and water conservation zones were investigated using a Geo-detector model, considering population, hydrological, topographic, soil types, and vegetation types. The results were as follows： ① The NDVI in Shandong Province from 2000 to 2020 showed a fluctuating upward trend with significant seasonal characteristics that varied from different zones. The annual NDVI change showed a trend of single-peak in the Ⅲ-4-2t, Ⅲ-4-1xt, and Ⅲ-5-2w but showed a trend of double-peak in the Ⅲ-5-3fn. ② Regarding the spatial distribution, the NDVI was higher in the west-north and west-south areas and lower in the north and coastal areas. During the 21 years, the primary type of NDVI change was "medium-high coverage → high coverage," especially in the northeastern part of the soil conservation area of the Ⅲ-4-2t, the western part of the Ⅲ-4-1xt, and the ecological maintenance area of the Ⅲ-5-2w. Overall, 61.47% of the area had a positive trend of NDVI change with the gravity center of high coverage mitigating to the northeast, and the ecological environment was improved. ③ Soil types and population density were the dominant factors affecting NDVI in Shandong Province, with q values of 0.174 and 0.130, respectively. The chief factor in the Ⅲ-5-3fn, Ⅲ-4-2t, and Ⅲ-4-1xt was population density, with q values higher than 0.22, and the dominant factors in the Ⅲ-5-2w were soil types and vegetation types, with q values of 0.326 and 0.227, respectively. The interaction of the two factors enhanced the influence of the single factor, and the relationship between the influencing factors showed two-factor enhancement and nonlinear enhancement. The q -value of population density ∩ relative humidity was the highest, with a value of 0.257 in the Ⅲ-5-3fn. The q -value of population density ∩ soil types was the highest in the Ⅲ-4-2t and Ⅲ-4-1xt, reaching 0.297 and 0.378, respectively. The q -value of soil types ∩ vegetation types was the highest, with a value of 0.444 in the Ⅲ-5-2w. The results are expected to provide valuable references for improving the ecological environment of Shandong Province and lay a scientific foundation to make different conservation strategies for the individual soil and water conservation zones.

This study aims to test the hypothesis that disease duration may affect the response to generic tofacitinib (TOF) and investigate the influence of concomitant medications with TOF on elderly rheumatoid arthritis (RA). This study retrospectively collected 76 elderly patients (age > 60) treated with TOF from 2019 to 2023 and grouped them according to age of disease onset. Data were collected from baseline to the last follow-up visit within 24 months. The demographic characteristics and follow-up results were compared. TOF retention and the effect of concomitant drugs (methotrexate, MTX, prednisone) were analyzed using Kaplan-Meier plots and COX regression analysis. Canonical correlation analysis (CCA) was used to explore the correlation among demographic characteristics, medication regimen, and improved clinical outcomes. There was no significant difference in the proportion of patients achieving low disease activity (LDA) between different disease duration groups. Patients in the group of MTX had a shorter time of using TOF in follow-up (log-rank p = 0.041). Prednisone dosage at baseline had a predictive value for functionally disabled situation. We found significant associations between discontinuation of TOF in the last follow-up and getting LDA. A total result of CCA yielded a significant positive correlation with set 1 (demographic characteristics and medication regimen) and set 2 (improved clinical outcomes) (canonical coefficient = 0.887, p < 0.001). Disease duration may not affect response to generic TOF and medication regimen was the factor related to efficacy of generic TOF in elderly RA in the real world. Demographic characteristics and medication regimen were correlated positively with improved clinical outcomes. Key Points • There is scarce data from the western area of China regarding the use of tofacitinib in elderly rheumatoid arthritis patients, despite widespread use. • In this retrospective analysis of 76 elderly patients at a single center, we found disease duration may not affect response to generic TOF. • Concomitant MTX might contribute to better control of the disease activity. • Concomitant prednisone dosage at baseline was the independent risk factor for functionally disabled situation., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Sepsis and septic shock are critical medical conditions characterized by a systemic inflammatory response to infection, significantly contributing to global mortality rates. The progression to multiple organ dysfunction syndrome (MODS) represents the most severe complication of sepsis and markedly increases clinical mortality. Central to the pathophysiology of sepsis, endothelial cells play a crucial role in regulating microcirculation and maintaining barrier integrity across various organs and tissues. Recent studies have underscored the pivotal role of endothelial function in the development of sepsis-induced MODS. This review aims to provide a comprehensive overview of the pathophysiology of sepsis-induced MODS, with a specific focus on endothelial dysfunction. It also compiles compelling evidence regarding potential small molecules that could attenuate sepsis and subsequent multi-organ damage by modulating endothelial function. Thus, this review serves as an essential resource for clinical practitioners involved in the diagnosing, managing, and providing intensive care for sepsis and associated multi-organ injuries, emphasizing the importance of targeting endothelial cells to enhance outcomes of the patients., Competing Interests: Declaration of Competing Interest These authors declared that there are no known conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Although the Japanese encephalitis virus (JEV) infects various cell types, its receptor molecules are still not clearly understood. In our laboratory's prior research, Rab4b was identified as a potential host factor that facilitates JEV infection in PK15 cells, utilizing a genome-wide CRISPR/Cas9 knockout library (PK-15-GeCKO). To further explore the effect of Rab4b on JEV replication, we used the Rab4b knockout PK15 cell line using the CRISPR/Cas9 technology and overexpressing the Rab4b PK15 cell line, with IFA, RT-qPCR, and Western blot to study the effect of Rab4b on viral replication in the whole life cycle of the JEV. The results show that the knockout of Rab4b inhibited the replication of the JEV in PK15 cells, and the overexpression of Rab4b promoted the replication of the JEV in PK15 cell lines. Furthermore, we demonstrated for the first time that host factor Rab4b facilitates the adsorption, internalization, assembly, and release of the JEV, thereby promoting JEV replication. This study enriches the regulatory network between the JEV and host factors and lays the experimental foundation for further understanding of the function of the Rab4b protein.

Sphagnum palustre L. is a Chinese herbal medicine with a long history, however, few studies have been performed on its chemical composition and active effects. In this study, we investigated the composition and antibacterial and antioxidant capacities of extracts obtained from Sphagnum palustre L. phytosomes extracted with conventional solvents (water, methanol, and ethanol) and two different hydrogen bond donors (citric acid and 1,2-propanediol) modified with choline chloride-type deep eutectic solvents (DESs). The results show that Sphagnum palustre extracts contained 253 compounds, including citric acid, ethyl maltol, and thymol. The highest total phenolic content (TPC) was obtained with a DES extraction method combining 1,2-propanediol and choline chloride (39.02 ± 7.08 mg gallic acid equivalent/g dried weight (DW). This shows the composition of Sphagnum palustre as a natural product and the application of DESs in the extraction of active ingredients, demonstrating the potential of peat moss extracts in cosmetics and health products.

Sudden cardiac death (SCD) is responsible for a high percentage of cardiovascular fatalities, with ventricular arrhythmias being the most common cause. Despite numerous clinically available antiarrhythmic drugs (AADs), AADs retain some undesirable arrhythmic effects, and their inappropriate use can lead to severe adverse reactions. The exploration of new therapeutic options against arrhythmias with fewer unreceptive effects is of utmost importance. The ethanolic extracts of seven Cupressaceae species, namely, Chamaecyparis obtusa , Juniperus chinensis (L.) Ant., Sabina chinensis (L.) Ant. cv. Kaizuca, Platycladus orientalis (L.) Franco, Juniperus sabina L., Fokienia hodginsii , and Juniperus chinensis 'Pyramidalis' were investigated for their pharmacological effects on barium chloride (BaCl 2 )-induced arrhythmia using normal II lead electrocardiogram (ECG) measurements in a mouse model. According to the ECG profiles, pretreatment with C. obtusa , P. orientalis , and J. sabina extracts provoked dose-dependent protection against BaCl 2 -induced arrhythmia, while pretreatment with the other four species and amiodarone did not exert cardioprotective effects. The treatment effects were confirmed using a rat model. The therapeutic effects of C. obtusa , P. orientalis , and J. sabina extracts on the M2 and M3 receptors but not the M1 receptor were mediated by the inhibition of the M2 receptor blocker (methoctramine tetrahydrochloride), M3 antagonist (4-DAMP), or M1 receptor blocker (pirenzepine dihydrochloride). This first-line evidence illustrates that certain Cupressaceae species possess active antiarrhythmic components. The first line of key findings revealed that active components of certain Cupressaceae species have cardioprotective effects, suggesting that these innovative phytochemicals have promising potential for preventing the occurrence of cardiac arrhythmia and reducing sudden cardiac death.

As China strives to balance rapid urbanization with environmental conservation, increasing attention is being paid to the pursuit of green production efficiency (GPE) in the real estate industry. The undesirable super-SBM model was used to calculate the GPE of China's real estate industry from 2001 to 2020. Additionally, GPE spatial distribution characteristics in China's real estate industry were analyzed using the standard deviation ellipse (SDE), Moran's index, Theil index, random kernel density estimation (RKDA), and spatial Markov chain (SMC) methods. The GPE exhibited a U-shaped trend, with 2008 as the inflection point, first decreasing and then increasing. It reached a maximum value of 0.747 in 2020. The Theil index increased from 0.043 to 0.121 nationwide, indicating the overall characteristics of low-level slow growth, and imbalance. Discrepancies in input-output scales, the southward shift of economic centers, and population movements contribute significantly to the disparities between the east and west, north and south, and regions divided by the Hu Huanyong Line (Hu Line). The GPE exhibited club convergence characteristics; however, polarization phenomena exist in local areas. Spatial spillover effects were also observed in GPE. Finally, we provide recommendations for promoting green development in the real estate industry, including green building technology, fiscal subsidy investment, and population migration management., (© 2024. The Author(s).)

FVP is a polysaccharide extracted from Flammulina velutipes with immunomodulatory, anti-tumor, and anti-oxidation activities. In this study, we obtained the crude polysaccharide FVP-C from the water extract of Flammulina velutipes, and its main component FVP-S1 was obtained after further purification. Upon structural identification, we found that FVP-C is a neutral polysaccharide, and FVP-S1 was an acidic golden mushroom polysaccharide, consisting of glucuronic acid, xylose, and glucose. Lung adenocarcinoma (A549) was treated with FVP-S1 and FVP-C, respectively, and we found that FVP-S1 and FVP-C inhibited the proliferation and migration ability of tumor cells, as well as changed the morphology of the tumor cells and caused chromosome sheteropythosis, among which FVP-S1 had the best inhibition effect. The results of flow cytometry experiments and mitochondrial membrane potential, RT-qPCR, and Western blot showed that FVP-S1 and FVP-C were able to decrease the mitochondrial membrane potential, increase the expression level of apoptotic proteins Casepase-3 and Casepase-9 proteins, and at the same time, increase the ratio of Bax and Bcl-2, which promoted apoptosis of tumor cells. In conclusion, these data indicated that FVP-S1 and FVP-C were able to induce apoptosis in A549 cells through the mitochondrial pathway, which played an important role in inhibiting tumor cells., (© 2024. The Author(s).)

Owing to the considerable potential of photoelectrochemical (PEC) sensors, they have gained significant attention in the analysis of biological, environmental, and food markers. However, the limited charge mass transfer efficiency and rapid recombination of electron hole pairs have become obstacles in the development of PEC sensors. In this case, considering the unique advantages of carbon-based materials, they can be used as photosensitizers, supporting materials and conductive substrates and coupled with semiconductors to prepare composite materials, solving the above problems. In addition, there are many types of carbon materials, which can have semiconductor properties and form heterojunctions after coupling with semiconductors, effectively promoting the separation of electron hole pairs. Herein, we aimed to provide a comprehensive analysis of reports on carbon-based PEC sensors by introducing their research and application status and discussing future development trends in this field. In particular, the types and performance improvement strategies of carbon-based electrodes and the working principles of carbon-based PEC sensors are explained. Furthermore, the applications of carbon-based photoelectric sensors in environmental monitoring, biomedicine, and food detection are highlighted. Finally, the current limitations in the research on carbon-based PEC sensors are emphasized and the need to enhance the sensitivity and selectivity through material modification, structural design, improved device performance, and other strategies are emphasized.

Background: Abdominal aortic aneurysm (AAA) is a severe aortic disease without effective pharmacological approaches. The nuclear hormone receptor LXRα (liver X receptor α), encoded by the NR1H3 gene, serves as a critical transcriptional mediator linked to several vascular pathologies, but its role in AAA remains elusive., Methods: Through integrated analyses of human and murine AAA gene expression microarray data sets, we identified NR1H3 as a candidate gene regulating AAA formation. To investigate the role of LXRα in AAA formation, we used global Nr1h3 -knockout and vascular smooth muscle cell-specific Nr1h3 -knockout mice in 2 AAA mouse models induced with angiotensin II (1000 ng·kg·min; 28 days) or calcium chloride (CaCl 2 ; 0.5 mol/L; 42 days)., Results: Upregulated LXRα was observed in the aortas of patients with AAA and in angiotensin II- or CaCl 2 -treated mice. Global or vascular smooth muscle cell-specific Nr1h3 knockout inhibited AAA formation in 2 mouse models. Loss of LXRα function prevented extracellular matrix degeneration, inflammation, and vascular smooth muscle cell phenotypic switching. Uhrf1 , an epigenetic master regulator, was identified as a direct target gene of LXRα by integrated analysis of transcriptome sequencing and chromatin immunoprecipitation sequencing. Susceptibility to AAA development was consistently enhanced by UHRF1 (ubiquitin-like containing PHD and RING finger domains 1) in both angiotensin II- and CaCl 2 -induced mouse models. We then determined the CpG methylation status and promoter accessibility of UHRF1-mediated genes using CUT&Tag (cleavage under targets and tagmentation), RRBS (reduced representation bisulfite sequencing), and ATAC-seq (assay for transposase-accessible chromatin with sequencing) in vascular smooth muscle cells, which revealed that the recruitment of UHRF1 to the promoter of miR-26b led to DNA hypermethylation accompanied by relatively closed chromatin states, and caused downregulation of miR-26b expression in AAA. Regarding clinical significance, we found that underexpression of miR-26b-3p correlated with high risk in patients with AAA. Maintaining miR-26b-3p expression prevented AAA progression and alleviated the overall pathological process., Conclusions: Our study reveals a pivotal role of the LXRα/UHRF1/miR-26b-3p axis in AAA and provides potential biomarkers and therapeutic targets for AAA., Competing Interests: Disclosures None.

Analgesic creams find widespread application as adjuncts for localized anesthesia prior to surgical procedures. Nevertheless, the onset of analgesic action is protracted due to the skin barrier's inherent characteristics, which necessitates prolonged intervals of patient and clinician waiting, consequently impinging upon patient compliance and clinician workflow efficiency. In this work, a biodegradable microneedles (MNs) patch was introduced to enhance the intradermal administration of lidocaine cream to achieve rapid analgesia through a minimally invasive and conveniently accessible modality. The polylactic acid (PLA) MNs were mass-produced using a simple hot-pressing method and served the purpose of creating microchannels across the skin's surface for rapid absorption of lidocaine cream. Optical and electron microscopes were applied to meticulously scrutinize the morphology of the fabricated MNs, and the comprehensive penetration tests involving dynamometer tests, evaluation on porcine cadaver skin, artificial film, optical coherence tomography (OCT), transepidermal water loss, and analysis on rats' skins, demonstrated the robust mechanical strength of PLA MNs for successful intradermal penetration. The behavioral pain sensitivity tests on living rats using Von Frey hair filaments revealed that the MN-assisted lidocaine treatment expeditiously accelerated the onset of action from 40 to 10 min and substantially enhanced the efficacy of localized anesthesia. Furthermore, different treatment protocols encompassing the sequence of drug application relative to MN treatment, MN dimensions, and the frequency of MN insertions exhibited noteworthy influence on the resultant local anesthesia efficacy. Together, these results demonstrated that the lidocaine cream followed by diverse PLA MN treatments would be a promising strategy for rapid clinical local anesthesia with wide-ranging applications., (© 2024. Controlled Release Society.)

Long-term consumption of Western-style diet (WSD) can lead to metabolic disorders and dysbiosis of gut microbiota, presenting a critical risk factor for various chronic conditions such as fatty liver disease. In the present study, we investigated the beneficial role of co-fermented whole grain quinoa and black barley with Lactobacillus kisonensis on rats fed a WSD. Male Sprague-Dawley (SD) rats, aged six weeks and weighing 180 ± 10 g, were randomly assigned to one of three groups: the normal control group (NC, n = 7), the WSD group (HF, n = 7), and the WSD supplemented with a co-fermented whole grain quinoa with black barley (FQB) intervention group (HFF, n = 7). The findings indicated that FQB was effective in suppressing body weight gain, mitigating hepatic steatosis, reducing perirenal fat accumulation, and ameliorating pathological damage in the livers and testicular tissues of rats. Additionally, FQB intervention led to decreased levels of serum uric acid (UA), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). These advantageous effects can be ascribed to the regulation of FQB on gut microbiota dysbiosis, which includes the restoration of intestinal flora diversity, reduction of the F/B ratio, and promotion of probiotics abundance, such as Akkermansia and [Ruminococcus] at the genus level. The study employed the UPLC-Q-TOF-MS E technique to analyze metabolites in fecal and hepatic samples. The findings revealed that FQB intervention led to a regression in the levels of specific metabolites in feces, including oxoadipic acid and 20a, 22b-dihydroxycholesterol, as well as in the liver, such as pyridoxamine, xanthine and xanthosine. The transcriptome sequencing of liver tissues revealed that FQB intervention modulated the mRNA expression of specific genes, including Cxcl12, Cidea, and Gck, known for their roles in anti-inflammatory and anti-insulin resistance mechanisms in the context of WSD. Our findings indicate that co-fermented whole-grain quinoa with black barley has the potential to alleviate metabolic disorders and chronic inflammation resulting from the consumption of WSD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Oxidative stress and neuroinflammation in the aging brain are correlated with the development of neurodegenerative diseases, such as Alzheimer's disease (AD). The blood-brain barrier (BBB) poses a significant challenge to the effective delivery of therapeutics for AD. Prior research has demonstrated that menthol (Men) can augment the permeability of the BBB. Consequently, in the current study, we modified Men on the surface of liposomes to construct menthol-modified quercetin liposomes (Men-Qu-Lips), designed to cross the BBB and enhance quercetin (Qu) concentration in the brain for improved therapeutic efficacy. The experimental findings indicate that Men-Qu-Lips exhibited good encapsulation efficiency and stability, successfully crossed the BBB, improved oxidative stress and neuroinflammation in the brains of aged mice, protected neurons, and enhanced their learning and memory abilities.

Purpose: This study aimed to investigate the prognostic value of alpha-fetoprotein (AFP) ratio in patients with AFP-negative hepatocellular carcinoma (HCC)., Patients and Methods: We retrospectively analyzed 600 AFP-negative HCC patients who underwent hepatectomy. The AFP ratio was calculated as the ratio of AFP level 1 week before surgery to the level 20-40 days after hepatectomy. Immunohistochemistry assay was used to assess protein expression in HCC tissue. The primary outcome measures were overall survival (OS) and disease-free survival (DFS)., Results: The study found that a cutoff value of 1.6 ng/ml for AFP ratio, determined using X-tile software, was optimal for predicting prognosis. Patients with a high AFP ratio had a worse prognosis compare to those with a low AFP ratio (DFS, P = .026; OS, P = .034). Patients with a high AFP ratio had a worse prognosis compared to those with a low AFP ratio. Multivariate analysis revealed that AFP ratio >1.6, negative HepPar-1 expression, and vascular invasion were independent predictors of both DFS and OS. Vascular invasion had a higher area under the curve (AUC) than AFP ratio and HepPar-1 expression in predicting recurrence and death. The combination of AFP ratio, HepPar-1 expression, and vascular invasion provided better predictive accuracy for DFS and OS., Conclusion: The AFP ratio is a potential prognostic marker for AFP-negative HCC patients after hepatectomy. Combining the analysis of AFP ratio with HepPar-1 expression and vascular invasion can enhance the accuracy of predicting prognosis in these patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: All methods in this research were carried out in accordance with relevant guidelines and regulations.

Non-communicable diseases (NCDs), including cardiovascular diseases, cancer, metabolic diseases, and skeletal diseases, pose significant challenges to public health worldwide. The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage. Nuclear factor erythroid 2-related factor 2 (Nrf2), a critical transcription factor, plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury. Therefore, Nrf2-targeting therapies hold promise for preventing and treating NCDs. Quercetin (Que) is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties. It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation. Que modulates mitochondrial function, apoptosis, autophagy, and cell damage biomarkers to regulate oxidative stress and inflammation, highlighting its efficacy as a therapeutic agent against NCDs. Here, we discussed, for the first time, the close association between NCD pathogenesis and the Nrf2 signaling pathway, involved in neurodegenerative diseases (NDDs), cardiovascular disease, cancers, organ damage, and bone damage. Furthermore, we reviewed the availability, pharmacokinetics, pharmaceutics, and therapeutic applications of Que in treating NCDs. In addition, we focused on the challenges and prospects for its clinical use. Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Authors.)

Up to 80% of Parkinson's disease patients develop dementia, but time to dementia varies widely from motor symptom onset. Dementia with Lewy bodies presents with clinical features similar to Parkinson's disease dementia, but cognitive impairment precedes or coincides with motor onset. It remains controversial whether dementia with Lewy bodies and Parkinson's disease dementia are distinct conditions or represent part of a disease spectrum. The biological mechanisms underlying disease heterogeneity, in particular the development of dementia, remain poorly understood, but will likely be the key to understanding disease pathways and, ultimately, therapy development. Previous genome-wide association studies in Parkinson's disease and dementia with Lewy bodies/Parkinson's disease dementia have identified risk loci differentiating patients from controls. We collated data for 7804 patients of European ancestry from Tracking Parkinson's, The Oxford Discovery Cohort, and Accelerating Medicine Partnership-Parkinson's Disease Initiative. We conducted a discrete phenotype genome-wide association study comparing Lewy body diseases with and without dementia to decode disease heterogeneity by investigating the genetic drivers of dementia in Lewy body diseases. We found that risk allele rs429358 tagging APOEe4 increases the odds of developing dementia, and that rs7668531 near the MMRN1 and SNCA-AS1 genes and an intronic variant rs17442721 tagging LRRK2 G2019S on chromosome 12 are protective against dementia. These results should be validated in autopsy-confirmed cases in future studies., Competing Interests: H.R.M. is employed by UCL. In the last 12 months, he reports paid consultancy from Roche, Aprinoia, AI Therapeutics and Amylyx; lecture fees/honoraria from BMJ, Kyowa Kirin and Movement Disorders Society; and research grants from Parkinson's UK, Cure Parkinson's Trust, PSP Association, Medical Research Council and Michael J. Fox Foundation. H.R.M. is a co-applicant on a patent application related to C9ORF72—Method for diagnosing a neurodegenerative disease (PCT/GB2012/052140)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Thrombocytopenia 2, an autosomal dominant inherited disease characterized by moderate thrombocytopenia, predisposition to myeloid malignancies and normal platelet size and function, can be caused by 5'-untranslated region (UTR) point mutations in ankyrin repeat domain containing 26 (ANKRD26). Runt related transcription factor 1 (RUNX1) and friend leukemia integration 1 (FLI1) have been identified as negative regulators of ANKRD26 . However, the positive regulators of ANKRD26 are still unknown., Aim: To prove the positive regulatory effect of GATA binding protein 2 (GATA2) on ANKRD26 transcription., Methods: Human induced pluripotent stem cells derived from bone marrow (hiPSC-BM) and urothelium (hiPSC-U) were used to examine the ANKRD26 expression pattern in the early stage of differentiation. Then, transcriptome sequencing of these iPSCs and three public transcription factor (TF) databases (Cistrome DB, animal TFDB and ENCODE) were used to identify potential TF candidates for ANKRD26 . Furthermore, overexpression and dual-luciferase reporter experiments were used to verify the regulatory effect of the candidate TFs on ANKRD26 . Moreover, using the GENT2 platform, we analyzed the relationship between ANKRD26 expression and overall survival in cancer patients., Results: In hiPSC-BMs and hiPSC-Us, we found that the transcription levels of ANKRD26 varied in the absence of RUNX1 and FLI1. We sequenced hiPSC-BM and hiPSC-U and identified 68 candidate TFs for ANKRD26 . Together with three public TF databases, we found that GATA2 was the only candidate gene that could positively regulate ANKRD26 . Using dual-luciferase reporter experiments, we showed that GATA2 directly binds to the 5'-UTR of ANKRD26 and promotes its transcription. There are two identified binding sites of GATA2 that are located 2 kb upstream of the TSS of ANKRD26 . In addition, we discovered that high ANKRD26 expression is always related to a more favorable prognosis in breast and lung cancer patients., Conclusion: We first discovered that the transcription factor GATA2 plays a positive role in ANKRD26 transcription and identified its precise binding sites at the promoter region, and we revealed the importance of ANKRD26 in many tissue-derived cancers., 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.)