Effects of fancy rope-skipping on motor coordination and selective attention in children aged 7-9 years: a quasi-experimental study.

Introduction: Recent studies have emphasized the intricate connection between exercise and cognition, focusing on specific cognitive processes and their correlations with specific motor skills. However, research on the impact of the qualitative aspects of movement on both short- and long-term cognitive performance is limited. In this quasi-experimental study, we investigate the impact of a 10-week fancy rope-skipping intervention on motor coordination and selective attention of 7-9-year-old children. Methods: A total of 60 primary school students from Changbin School in Haikou participated and completed the study from October to December 2022. The 60 participants were divided into a fancy rope-skipping group and a control group. Children's motor coordination was assessed using the Körperkoordinations Test für Kinder (KTK), while selective attention was evaluated using the d2 Test of Attention. Children were assessed at baseline and after the 10-week intervention. Results: Compared with the control group, the scores for the total KTK and for the hopping for height, jumping sideways, and moving sideways sub-items were significantly higher in the rope-skipping group after the intervention, with a significant interaction effect between time and intervention. Attention concentration improved in the rope-skipping group and had a significant interaction effect between time and intervention compared with the control group; the effects of the intervention on other aspects of selective attention were unclear. Conclusions: Our study suggests that a 10-week fancy rope-skipping intervention may potentially enhance motor coordination and selective attention accuracy in children aged 7-9 years.

Expert consensus on the diagnosis and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children.

BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is a significant contributor to community-acquired pneumonia among children. Since 1968, when a strain of M. pneumoniae resistant to macrolide antibiotics was initially reported in Japan, macrolide-resistant M. pneumoniae (MRMP) has been documented in many countries worldwide, with varying incidence rates. MRMP infections lead to a poor response to macrolide antibiotics, frequently resulting in prolonged fever, extended antibiotic treatment, increased hospitalization, intensive care unit admissions, and a significantly higher proportion of patients receiving glucocorticoids or second-line antibiotics. Since 2000, the global incidence of MRMP has gradually increased, especially in East Asia, which has posed a serious challenge to the treatment of M. pneumoniae infections in children and attracted widespread attention from pediatricians. However, there is still no global consensus on the diagnosis and treatment of MRMP in children. METHODS: We organized 29 Chinese experts majoring in pediatric pulmonology and epidemiology to write the world's first consensus on the diagnosis and treatment of pediatric MRMP pneumonia, based on evidence collection. The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, CNKI, Medline, and the Cochrane Library. We used variations in terms for "macrolide-resistant", "Mycoplasma pneumoniae", "MP", "M. pneumoniae", "pneumonia", "MRMP", "lower respiratory tract infection", "Mycoplasma pneumoniae infection", "children", and "pediatric". RESULTS: Epidemiology, pathogenesis, clinical manifestations, early identification, laboratory examination, principles of antibiotic use, application of glucocorticoids and intravenous immunoglobulin, and precautions for bronchoscopy are highlighted. Early and rapid identification of gene mutations associated with MRMP is now available by polymerase chain reaction and fluorescent probe techniques in respiratory specimens. Although the resistance rate to macrolide remains high, it is fortunate that M. pneumoniae still maintains good in vitro sensitivity to second-line antibiotics such as tetracyclines and quinolones, making them an effective treatment option for patients with initial treatment failure caused by macrolide antibiotics. CONCLUSIONS: This consensus, based on international and national scientific evidence, provides scientific guidance for the diagnosis and treatment of MRMP in children. Further studies on tetracycline and quinolone drugs in children are urgently needed to evaluate their effects on the growth and development. Additionally, developing an antibiotic rotation treatment strategy is necessary to reduce the prevalence of MRMP strains.

Performance Correction and Parameters Identification Considering Non-Uniform Electric Field in Cantilevered Piezoelectric Energy Harvesters.

In the current electromechanical model of cantilevered piezoelectric energy harvesters, the assumption of uniform electric field strength within the piezoelectric layer is commonly made. This uniform electric field assumption seems reasonable since the piezoelectric layer looks like a parallel-plate capacitor. However, for a piezoelectric bender, the strain distribution along the thickness direction is not uniform, which means the internal electric field generated by the spontaneous polarization cannot be uniform. In the present study, a non-uniform electric field in the piezoelectric layer is resolved using electrostatic equilibrium equations. Based on these, the traditional distributed parameter electromechanical model is corrected and simplified to a practical single mode one. Compared with a traditional model adopting a uniform electric field, the bending stiffness term involved in the electromechanical governing equations is explicitly corrected. Through comparisons of predicted power output with two-dimensional finite element analysis, the results show that the present model can better predict the power output performance compared with the traditional model. It is found that the relative corrections to traditional model have nothing to do with the absolute dimensions of the harvesters, but only relate to three dimensionless parameters, i.e., the ratio of the elastic layer's to the piezoelectric layer's thickness; the ratio of the elastic modulus of the elastic layer to the piezoelectric layer; and the piezoelectric materials' electromechanical coupling coefficient squared, k312. It is also found that the upper-limit relative corrections are only related to k312, i.e., the higher k312 is, the larger the upper-limit relative corrections will be. For a PZT-5 unimorph harvester, the relative corrections of bending stiffness and corresponding resonant frequency are up to 17.8% and 8.5%, respectively. An inverse problem to identify the material parameters based on experimentally obtained power output performance is also investigated. The results show that the accuracy of material parameters identification is improved when considering a non-uniform electric field.

Activation of limbal epithelial proliferation is partly controlled by the ACE2-LCN2 pathway.

In response to corneal injury, an activation of corneal epithelial stem cells and their direct progeny the early transit amplifying (eTA) cells to rapidly proliferate is critical for proper re-epithelialization. Thus, it is important to understand how such stem/eTA cell activation is regulated. Angiotensin-converting enzyme 2 (ACE2) is predominantly expressed in the stem/eTA-enriched limbal epithelium but its role in the limbal epithelium was unclear. Single cell RNA sequencing (scRNA-seq) suggested that Ace2 involved the proliferation of the stem/eTA cells. Ace2 was reduced following corneal injury. Such reduction enhanced limbal epithelial proliferation and downregulated LCN2, a negative regulator of proliferation in a variety of tissues, via upregulating TGFA and consequently activating epidermal growth factor receptor (EGFR). Inhibition of EGFR or overexpression of LCN2 reversed the increased proliferation in limbal epithelial cells lacking ACE2. Our findings demonstrate that after corneal injury, ACE2 is downregulated, which activates limbal epithelial cell proliferation via a TGFA/EGFR/LCN2 pathway.

Surface Molecularly Engineered Mitochondria Conduct Immunophenotype Repolarization of Tumor-Associated Macrophages to Potentiate Cancer Immunotherapy.

Reprogramming tumor-associated macrophages (TAMs) to an inflammatory phenotype effectively increases the potential of immune checkpoint blockade (ICB) therapy. Artificial mitochondrial transplantation, an emerging and safe strategy, has made brilliant achievements in regulating the function of recipient cells in preclinic and clinic, but its performance in reprogramming the immunophenotype of TAMs has not been reported. Here, the metabolism of M2 TAMs is proposed resetting from oxidative phosphorylation (OXPHOS) to glycolysis for polarizing M1 TAMs through targeted transplantation of mannosylated mitochondria (mPEI/M1mt). Mitochondria isolated from M1 macrophages are coated with mannosylated polyethyleneimine (mPEI) through electrostatic interaction to form mPEI/M1mt, which can be targeted uptake by M2 macrophages expressed a high level of mannose receptors. Mechanistically, mPEI/M1mt accelerates phosphorylation of NF-κB p65, MAPK p38 and JNK by glycolysis-mediated elevation of intracellular ROS, thus prompting M1 macrophage polarization. In vivo, the transplantation of mPEI/M1mt excellently potentiates therapeutic effects of anti-PD-L1 by resetting an antitumor proinflammatory tumor microenvironment and stimulating CD8 and CD4 T cells dependent immune response. Altogether, this work provides a novel platform for improving cancer immunotherapy, meanwhile, broadens the scope of mitochondrial transplantation technology in clinics in the future.

Gut-derived memory γδ T17 cells exacerbate sepsis-induced acute lung injury in mice.

Sepsis is a critical global health concern linked to high mortality rates, often due to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). While the gut-lung axis involvement in ALI is recognized, direct migration of gut immune cells to the lung remains unclear. Our study reveals sepsis-induced migration of γδ T17 cells from the small intestine to the lung, triggering an IL-17A-dominated inflammatory response in mice. Wnt signaling activation in alveolar macrophages drives CCL1 upregulation, facilitating γδ T17 cell migration. CD44+ Ly6C- IL-7Rhigh CD8low cells are the primary migratory subtype exacerbating ALI. Esketamine attenuates ALI by inhibiting pulmonary Wnt/ß-catenin signaling-mediated migration. This work underscores the pivotal role of direct gut-to-lung memory γδ T17 cell migration in septic ALI and clarifies the importance of localized IL-17A elevation in the lung.

Subway Fine Particles (PM2.5)-Induced Pro-Inflammatory Response Triggers Airway Epithelial Barrier Damage Through the TLRs/NF-κB-Dependent Pathway In Vitro.

Subways are widely used in major cities around the world, and subway fine particulate matter (PM2.5) is the main source of daily PM2.5 exposure for urban residents. Exposure to subway PM2.5 leads to acute inflammatory damage in humans, which has been confirmed in mouse in vivo studies. However, the concrete mechanism by which subway PM2.5 causes airway damage remains obscure. In this study, we found that subway PM2.5 triggered release of pro-inflammatory cytokines such as interleukin 17E, tumor necrosis factor α, transforming growth factor ß, and thymic stromal lymphopoietin from human bronchial epithelial cells (BEAS-2B) in a dose-effect relationship. Subsequently, supernatant recovered from the subway PM2.5 group significantly increased expression of the aforementioned cytokines in BEAS-2B cells compared with the subway PM2.5 group. Additionally, tight junctions (TJs) of BEAS-2B cells including zonula occludens-1, E-cadherin, and occludin were decreased by subway PM2.5 in a dose-dependent manner. Moreover, supernatant recovered from the subway PM2.5 group markedly decreased the expression of these TJs compared with the control group. Furthermore, inhibitors of toll-like receptors (TLRs) and nuclear factor-kappa B (NF-κB), as well as chelate resins (e.g., chelex) and deferoxamine, remarkably ameliorated the observed changes of cytokines and TJs caused by subway PM2.5 in BEAS-2B cells. Therefore, these results suggest that subway PM2.5 induced a decline of TJs after an initial ascent of cytokine expression, and subway PM2.5 altered expression of both cytokines and TJs by activating TLRs/NF-κB-dependent pathway in BEAS-2B cells. The metal components of subway PM2.5 may contribute to the airway epithelial injury.

A Highly Sensitive 3D-Printed Flexible Sensor for Sensing Small Pressures in Deep-Sea High-Pressure Environment.

The origin of life on Earth is believed to be from the ocean, which offers abundant resources in its depths. However, deep-sea operations are limited due to the lack of underwater robots and rigid grippers with sensitive force sensors. Therefore, it is crucial for deep-sea pressure sensors to be integrated with mechanical hands for manipulation. Here, a flexible stress sensor is presented that can function effectively under high water pressure in the deep ocean. Inspired by biological structures found in the abyssal zone, our sensor is designed with an internal and external pressure balance structure (hollow interlocking spherical structure). The digital light processing (DLP) three-dimensional (3D) printing technology is utilized to construct this complex structure after obtaining optimized structural parameters using finite element simulation. The sensor exhibits linear sensitivity of 0.114 kPa-1 within the range of 0-15 kPa and has an extremely short response time of 32 ms, good dynamic-static load response capability, and excellent resistance cycling stability. It shows high sensitivity of 1.74 kPa-1 even under 30 MPa static water pressures and the theoretical working pressure can exceed 110 MPa, which provides a new solution for deep-sea robots.

Dehydration regulates structural reorganization of dynamic hydrogels.

The dehydration process is widely recognized as a significant phenomenon in nature. Hydrogels, which are important functional materials with high water content and crosslinked networks, encounter the issue of dehydration in their practical applications. Here, we report the distinctive anisotropic dehydration modality of dynamic hydrogels, which is fundamentally different from the more commonly observed isotropic dehydration of covalent hydrogels. Xerogels derived from dynamic hydrogel dehydration will fully cover a curved substrate surface and exhibit hollow structures with internal knots, in contrast to the bulk xerogels produced by covalent hydrogel dehydration. Depending on the competing cohesion of polymer chains and the adhesion at the hydrogel-substrate interface, the previously overlooked reorganization of polymer networks within dynamic hydrogels, triggered by dehydration-induced stress, has been discovered to regulate such macroscopic structural reconstruction for dynamic hydrogel dehydration. With the attached hydrogel-substrate interface, the surface microstructures of substrates can also be engraved onto xerogels with high resolution and on a large scale. This work will greatly enhance our understanding of the soft matter dehydration process and broaden the applications of dehydration technologies using water-containing materials.

Phytotoxic Isocassadiene-Type Diterpenoids from Tomato Fusarium Crown and Root Rot Pathogen Fusarium oxysporum f. sp. radicis-lycopersici.

Fusarium crown and root rot (FCRR) has emerged as a highly destructive soil-borne disease, posing a significant threat to the safe cultivation of tomatoes in recent years. The pathogen of tomato FCRR is Fusarium oxysporum f. sp. radicis-lycopersici (Forl). To explore potential phytotoxins from Forl, eight undescribed diterpenoids namely fusariumic acids A-H (1-8) were isolated. Their structures were elucidated by using spectroscopic data analyses, quantum chemical calculations, and X-ray crystallography. Fusariumic acids A (1) and C-H (3-8) were typical isocassadiene-type diterpenoids, while fusariumic acid B (2) contained a cage-like structure with an unusual 7,8-seco-isocassadiene skeleton. A biosynthetic pathway of 2 was proposed. Fusariumic acids A (1) and C-H (3-8) were further assessed for their phytotoxic effects on tomato seedlings at 200 µg/mL. Among them, fusariumic acid F (6) exhibited the strongest inhibition against the hypocotyl and root elongation of tomato seedlings, with inhibitory rates of 61.3 and 45.3%, respectively.

Structural Simplification of Podophyllotoxin: Discovery of γ-Butyrolactone Derivatives as Novel Antiviral Agents for Plant Protection.

Natural products are a valuable resource for the discovery of novel crop protection agents. A series of γ-butyrolactone derivatives, derived from the simplification of podophyllotoxin's structure, were synthesized and assessed for their efficacy against tobacco mosaic virus (TMV). Several derivatives exhibited notable antiviral properties, with compound 3g demonstrating the most potent in vivo anti-TMV activity. At 500 µg/mL, compound 3g achieved an inactivation effect of 87.8%, a protective effect of 71.7%, and a curative effect of 67.7%, surpassing the effectiveness of the commercial plant virucides ningnanmycin and ribavirin. Notably, the syn-diastereomer (syn-3g) exhibited superior antiviral activity compared to the anti-diastereomer (anti-3g). Mechanistic studies revealed that syn-3g could bind to the TMV coat protein and interfere with the self-assembly process of TMV particles. These findings indicate that compound 3g, with its simple chemical structure, could be a potential candidate for the development of novel antiviral agents for crop protection.

Effect and mechanism of curcumin on colon cancer cell senescence through early growth response 1 (EGR1).

Background: The expression level of early growth response 1 (EGR1) is elevated in colon cancer (CC) tissues and is closely associated with poor prognosis in colorectal cancer. However, the role of EGR1 as a transcription factor (TF) influencing cell senescence in the progression of CC remains largely unexplored. This study aims to investigate the impact of curcumin on colorectal cancer cell senescence by modulating EGR1. Methods: Genes associated with cell senescence were obtained from a public database, and ChIP-X predicted TFs were utilized. The R2 database was employed to examine the relationship between gene expression and survival. CC cell lines were transfected with plasmids to achieve stable expression. Stable transfected cell lines were screened, and changes in RNA and protein expression were assessed using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB) analysis. Senescence levels were measured by SA-ß-Gal staining. Cell proliferation and invasion capabilities were evaluated through soft agar and Matrigel invasion assays. Molecular docking was used to predict the interaction between curcumin and EGR1. Gene activity changes were detected using a dual luciferase reporter gene assay. Results: The results indicated that EGR1 was overexpressed in CC tissues and correlated with poor prognosis. As a TF, EGR1 negatively regulated the expression of telomerase reverse transcriptase (TERT) and sirtuin 6 (SIRT6) genes associated with cell senescence. Knocking down EGR1 increased the rate of cell senescence and inhibited cell proliferation and invasion. Curcumin inhibited the transcriptional activity of EGR1, thereby promoting cell senescence and inhibiting tumor progression. Conclusions: In conclusion, curcumin hampers the activity of TF EGR1, affecting the transcription and translation of target genes TERT and SIRT6, thus promoting cell senescence and inhibiting CC cell proliferation. These findings provide potential insights for targeted therapy of CC.

Involvement of LaeA and Velvet Proteins in Regulating the Production of Mycotoxins and Other Fungal Secondary Metabolites.

Fungi are rich sources of secondary metabolites of agrochemical, pharmaceutical, and food importance, such as mycotoxins, antibiotics, and antitumor agents. Secondary metabolites play vital roles in fungal pathogenesis, growth and development, oxidative status modulation, and adaptation/resistance to various environmental stresses. LaeA contains an S-adenosylmethionine binding site and displays methyltransferase activity. The members of velvet proteins include VeA, VelB, VelC, VelD and VosA for each member with a velvet domain. LaeA and velvet proteins can form multimeric complexes such as VosA-VelB and VelB-VeA-LaeA. They belong to global regulators and are mainly impacted by light. One of their most important functions is to regulate gene expressions that are responsible for secondary metabolite biosynthesis. The aim of this mini-review is to represent the newest cognition of the biosynthetic regulation of mycotoxins and other fungal secondary metabolites by LaeA and velvet proteins. In most cases, LaeA and velvet proteins positively regulate production of fungal secondary metabolites. The regulated fungal species mainly belong to the toxigenic fungi from the genera of Alternaria, Aspergillus, Botrytis, Fusarium, Magnaporthe, Monascus, and Penicillium for the production of mycotoxins. We can control secondary metabolite production to inhibit the production of harmful mycotoxins while promoting the production of useful metabolites by global regulation of LaeA and velvet proteins in fungi. Furthermore, the regulation by LaeA and velvet proteins should be a practical strategy in activating silent biosynthetic gene clusters (BGCs) in fungi to obtain previously undiscovered metabolites.

Dietary Fiber-Derived Microbial Butyrate Suppresses ILC2-Dependent Airway Inflammation in COPD.

Group 2 innate lymphoid cells (ILC2) strongly modulate COPD pathogenesis. However, the significance of microbiota in ILC2s remains unelucidated. Herein, we investigated the immunomodulatory role of short-chain fatty acids (SCFAs) in regulating ILC2-associated airway inflammation and explores its associated mechanism in COPD. In particular, we assessed the SCFA-mediated regulation of survival, proliferation, and cytokine production in lung sorted ILC2s. To elucidate butyrate action in ILC2-driven inflammatory response in COPD models, we administered butyrate to BALB/c mice via drinking water. We revealed that SCFAs, especially butyrate, derived from dietary fiber fermentation by gut microbiota inhibited pulmonary ILC2 functions and suppressed both IL-13 and IL-5 synthesis by murine ILC2s. Using in vivo and in vitro experimentation, we validated that butyrate significantly ameliorated ILC2-induced inflammation. We further demonstrated that butyrate suppressed ILC2 proliferation and GATA3 expression. Additionally, butyrate potentially utilized histone deacetylase (HDAC) inhibition to enhance NFIL3 promoter acetylation, thereby augmenting its expression, which eventually inhibited cytokine production in ILC2s. Taken together, the aforementioned evidences demonstrated a previously unrecognized role of microbial-derived SCFAs on pulmonary ILC2s in COPD. Moreover, our evidences suggest that metabolomics and gut microbiota modulation may prevent lung inflammation of COPD.

Augmentation of functional recovery via ROCK/PI3K/AKT pathway by Fasudil Hydrochloride in a rat sciatic nerve transection model.

Backgrounds: The functional recovery after peripheral nerve injury remains unsatisfactory. This study aims to perform a comprehensive evaluation of the efficacy of Fasudil Hydrochloride at treating the sciatic nerve transection injury in rats and the mechanism involved. Materials and methods: In animal experiments, 75 Sprague Dawley rats that underwent transection and repair of the right sciatic nerve were divided into a control, Fasudil, and Fas + LY group, receiving daily intraperitoneal injection of saline, Fasudil Hydrochloride (10 mg/kg), and Fasudil Hydrochloride plus LY294002 (5 mg/kg), respectively. At day 3 after surgery, the expression of ROCK2, p-PI3K, and p-AKT in L4-5 DRG and the lumbosacral enlargement was determined using Western blotting. At day 7 and 14, axon density in the distal stump was evaluated with immunostaining using the anti-Neurofilament-200 antibody. At day 30, retrograde tracing by injecting Fluoro-gold in the distal stump was performed. Three months after surgery, remyelination was analyzed with immostaining using the anti-MPZ antibody and the transmission electron microscope; Moreover, Motion-Evoked Potential, and recovery of sensorimotor functions was evaluated with a neuromonitor, Footprint, Hot Plate and Von Frey Filaments, respectively. Moveover, the Gastrocnemius muscles were weighed, and then underwent H＆E staining, and staining of the neuromuscular junction using α-Bungarotoxin to evaluate the extent of atrophy and degeneration of the endplates in the Gastrocnemius. In vitro, spinal motor neurons (SMNs) and dorsal root ganglia (DRG) were cultured to examine the impact of Fasudil Hydrochloride and LY294002 on the axon outgrowth. Results: Three days after injury, the expression of ROCK2 increased significantly (P＜0.01), and Fasudil application significantly increased the expression of p-PI3K and p-AKT in L4-6 DRG and the lumbosacral enlargement (P < 0.05). At day 7 and 14 after surgery, a higher axon density could be observed in the Fasudil group(P < 0.05). At day 30 after surgery, a larger number of motor and sensory neurons absorbing Fluoro-gold could be observed in the Fasudil group (P < 0.01) Three months after surgery, a greater thickness of myelin sheath could be observed in the Fasudil group (P < 0.05). The electrophysiological test showed that a larger amplitude of motion-evoked potential could be triggered in the Fasudil group (P < 0.01). Behavioral tests showed that a higher sciatic function index and a lower threshold for reacting to heat and mechanical stimuli could be measured in the Fasudil group. (P < 0.01). The wet weight ratio of the Gastrocnemius muscles and the area of the cross section of its myofibrils were greater in the Fasudil group (P < 0.01), which also demonstrated a higer ratio of axon-endplate connection and a larger size of endplates (P < 0.05). And there were no significant differences for the abovementioned parameters between the control and Fas + LY groups (P＞0.05). In vitro studies showed that Fasudil could significantly promote axon growth in DRG and SMNs, and increase the expression of p-PI3K and p-AKT, which could be abolished by LY294002 (P < 0.05). Conclusions: Fasudil can augment axon regeneration and remyelination, and functional recovery after sciatic nerve injury by activating the PI3K/AKT pathway. The translational potential of this article: The translation potential of this article is that we report for the first time that Fasudil Hydrochloride has a remarkable efficacy at improving axon regeneration and remyelination following a transection injury of the right sciatic nerve in rats through the ROCK/PI3K/AKT pathway, which has a translational potential to be used clinically to treat peripheral nerve injury.

Sex Hormones and Chronic Obstructive Pulmonary Disease: A Cross-Sectional Study and Mendelian Randomization Analysis.

Background: Sex steroid hormones, including testosterone and estradiol, play significant roles in various aspects of pulmonary health and diseases. However, although there were a few studies trying to link sex hormones with COPD, their effect remained limited due to small sample size and insufficient causal results. This study aims to investigate the association between sex hormones and chronic obstructive pulmonary disease (COPD) based on the National Health and Nutrition Examination Survey (NHANES) database and evaluate causality via a two-sample Mendelian randomization (MR). Methods: Data from NHANES 2013-2016 were enrolled for the cross-sectional study. The association between sex hormones and COPD was evaluated via multivariable logistic regression. Sex-stratified analysis, subgroup analyses and interaction tests were performed to further evaluate the correlation. For MR analysis, data were collected from genome-wide association studies and FinnGen datasets. The inverse-variance-weighted (IVW) approach, along with four other approaches, was applied in the analysis. Further sensitivity analysis was conducted to assess the existence of pleiotropy and heterogeneity. Results: 7,617 eligible participants were enrolled in the cross-sectional analysis. Negative associations were observed in both testosterone-COPD (OR 0.770, 95% CI 0.626, 0.948, p = 0.018) and estradiol-COPD (OR 0.794, 95% CI 0.688, 0.915, p = 0.005) relationships after covariate adjustments. However, the results from IVW-MR analysis showed that no causal relationship was observed in either the testosterone-COPD (OR 0.83, 95% CI 0.53, 1.29, p = 0.407) or estradiol-COPD (OR 0.74, 95% CI 0.23, 2.38, p = 0.616) relationship, which was also supported by the other four approaches (all p values > 0.05). Conclusion: Although a significant negative association was observed between sex hormones and COPD, the results of MR analysis did not support the causality of this relationship. Our study suggested that sex hormones may indirectly rather than directly affect the development of COPD via potential covariates, which warranted further investigations.

Discovery, Optimization, and Biological Evaluation of Novel Pyrazol-5-yl-phenoxybenzamide Derivatives as Potent Succinate Dehydrogenase Inhibitors.

The diphenyl ether molecular pharmacophore has played a significant role in the development of fungicidal compounds. In this study, a variety of pyrazol-5-yl-phenoxybenzamide derivatives were synthesized and evaluated for their potential to act as succinate dehydrogenase inhibitors (SDHIs). The bioassay results indicate certain compounds to display a remarkable and broad-spectrum in their antifungal activities. Notably, compound 12x exhibited significant in vitro activities against Valsa mali, Gaeumannomyces graminis, and Botrytis cinerea, with EC50 values of 0.52, 1.46, and 3.42 mg/L, respectively. These values were lower or comparable to those of Fluxapyroxad (EC50 = 12.5, 1.93, and 8.33 mg/L, respectively). Additionally, compound 12x showed promising antifungal activities against Sclerotinia sclerotiorum (EC50 = 0.82 mg/L) and Rhizoctonia solani (EC50 = 1.86 mg/L), albeit lower than Fluxapyroxad (EC50 = 0.23 and 0.62 mg/L). Further in vivo experiments demonstrated compound 12x to possess effective protective antifungal activities against V. mali and S. sclerotiorum at a concentration of 100 mg/L, with inhibition rates of 66.7 and 89.3%, respectively. In comparison, Fluxapyroxad showed inhibition rates of 29.2 and 96.4% against V. mali and S. sclerotiorum, respectively. Molecular docking analysis revealed that compound 12x interacts with SDH through hydrogen bonding, π-cation, and π-π interactions, providing insights into the probable mechanism of action. Furthermore, compound 12x exhibited greater binding energy and SDH enzyme inhibitory activity than Fluxapyroxad (ΔGcal = -46.8 kcal/mol, IC50 = 1.22 mg/L, compared to ΔGcal = -41.1 kcal/mol, IC50 = 8.32 mg/L). Collectively, our results suggest that compound 12x could serve as a promising fungicidal lead compound for the development of more potent SDHIs for crop protection.

Salinity-driven nitrogen removal and bacteria community compositions in microbial fuel cell-integrated constructed wetlands.

The effects of salinity gradients (500-4000 mg·L-1 NaCl) on electricity generation, nitrogen removal, and microbial community were investigated in a constructed wetland-microbial fuel cell (CW-MFC) system. The result showed that power density significantly increased from 7.77 mW m-2 to a peak of 34.27 mW m-2 as salinity rose, indicating enhanced electron transfer capabilities under saline conditions. At a moderate salinity level of 2000 mg·L-1 NaCl, the removal efficiencies of NH4+-N and TN reached their maximum at 77.34 ± 7.61% and 48.45 ± 8.14%, respectively. This could be attributed to increased microbial activity and the presence of critical nitrogen-removal organisms, such as Nitrospira and unclassified Betaproteobacteria at the anode, as well as Bacillus, unclassified Rhizobiales, Sphingobium, and Simplicispira at the cathode. Additionally, this salinity corresponded with the highest abundance of Exiguobacterium (3.92%), a potential electrogenic bacterium, particularly at the cathode. Other microorganisms, including Geobacter, unclassified Planctomycetaceae, and Thauera, adapted well to elevated salinity, thereby enhancing both electricity generation and nitrogen removal.

The application of pH-responsive hyaluronic acid-based essential oils hydrogels with enhanced anti-biofilm and wound healing.

pH could play vital role in the wound healing process due to the bacterial metabolites, which is one essential aspect of desirable wound dressings lies in being pH-responsive. This work has prepared a degradable hyaluronic acid hydrogel dressing with wound pH response-ability. The aldehyde-modified hyaluronic acid (AHA) was obtained, followed by complex mixture formation of eugenol and oregano antibacterial essential oil in the AHA-CMCS hydrogel through the Schiff base reaction with carboxymethyl chitosan (CMCS). This hydrogel composite presents pH-responsiveness, its disintegration mass in acidic environment (pH = 5.5) is 4 times that of neutral (pH = 7.2), in which the eugenol release rate increases from 37.6 % to 82.1 %. In vitro antibacterial and in vivo wound healing investigations verified that hydrogels loaded with essential oils have additional 5 times biofilm removal efficiency, and significantly accelerate wound healing. Given its excellent anti-biofilm and target-release properties, the broad application of this hydrogel in bacteria-associated wound management is anticipated.

Spatial scale effects on the value of ecosystem services in China's terrestrial area.

Identifying the response characteristics of ecosystem service value (ESV) to changes in spatial scales, known as spatial scale effects, is crucial in guiding the development of corresponding management strategies. This paper examines ESV in China's terrestrial area during the year 2020, revealing the spatial aggregation characteristics of ESV and the trade-off and synergistic relationships of ecosystem services at different spatial scales, ranging from 1 km × 1 km-10 km × 10 km, with a gradient of 1 km. The results indicate: 1) The distribution pattern of ESV in China's terrestrial area is "high in the southeast and low in the northwest." 2) The spatial characteristics of ESV in China's terrestrial area undergo a distinct transition at the 3 km × 3 km scale. In detail, the spatial clustering features show a trend of first rising and then falling with the increase in spatial scale, while the synergistic relationships between different ecosystem services strengthen and the trade-off relationships weaken with the increase of the spatial scale. These findings can inform the formulation of differentiated ecological protection compensation policies and enable cross-area trading of ecological values in China.