Arteriovenous Fistula Histology, Hemodynamics, and Wall Mechanics: A Case Report of Successful and Failed Access in a Single Patient.

The low 1-year patency rate of mature arteriovenous fistulas (AVFs) remains a significant clinical problem. Although vessel properties and biomechanics have been suggested to affect AVF function, understanding their roles in AVF patency failure is challenging owing to the heterogeneity within the patient population, including demographics and comorbid conditions. In this study, we present a case of a patient with 2 upper-arm AVFs with different 1-year patency outcomes and investigate whether they had different histologic features before the AVF creation surgery and biomechanics at 1 day and 6 weeks after the AVF creation surgery using magnetic resonance imaging-based fluid structure interaction simulations. Despite both AVFs being in the upper arm, created <1 year apart by the same surgeon, and having similar preoperative vessel diameters, the 1-year patent AVF had less preoperative intimal collagen and higher wall shear stress 1 day after AVF creation, when compared with the AVF that failed by 1 year. Thus, a low intimal collagen content before the AVF surgery and higher wall shear stress immediately after the AVF creation surgery may be important for long-term AVF patency and should be investigated with larger cohorts.

Hirudin enhances perforator flap survival: Clinical application report and mechanistic exploration.

BACKGROUND AND PURPOSE: Hirudin, a potent anticoagulant, is used in traditional Chinese medicine (TCM) to treat thrombotic conditions and prevent postoperative thrombosis. Coagulation-related vascular complications are a common cause of perforator flaps failure. This study explores hirudin's potential to enhance flap growth by mitigating coagulation-related issues. MATERIALS AND METHODS: Patients were divided into GroupⅠ(hirudin group) and GroupⅡ(control). Laboratory tests covered red blood cell count (RBC), hematocrit (HCT), platelet count (PLT), monocyte count (MONO), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and D-Dimer. Clinical parameters, including capillary refill time (CRT), flap swelling, and survival status, were evaluated. Animal experiments used Sprague-Dawley (SD) rats to establish random skin flaps. The experimental side received hirudin injection, while the control side received saline. Flaps were photographed to calculate survival rate, and CD31 immunohistochemical (IHC) analysis was performed to calculate microvessel density (MVD). RESULTS: The study, with 29 patients, found significant CRT differences between groups on postoperative days 2 and 6 (p = 0.027; p = 0.019), favoring GroupⅠ. Swelling severity varied significantly over time; GroupⅡhad more pronounced swelling. GroupⅠshowed superior flap growth with fewer complications, statistically significant (p = 0.033). Specific lab indicators (MONO, PT, and FIB) were significant at certain times. In animal experiments, the experimental side consistently had higher flap survival and slightly increased CD31 expression at various times, with higher MVD on days 2 and 6. CONCLUSIONS: Hirudin enhances flap survival through diverse mechanisms, supporting its role as a complementary approach in perforator flap surgeries.

Coronary Artery Tree Description and Lesion Evaluation (CatLet) score for functional evaluation of coronary stenosis: a comparison study with pressure wire fractional flow reserve.

Background: Pressure wire fractional flow reserve (FFR) and its derivatives, such as quantitative flow ratio (QFR), computational pressure flow-derived FFR (caFFR), coronary angiography-derived FFR (FFRangio), and computed tomography-derived FFR (FFRCT), have been validated for identifying functionally significant stenosis and guiding revascularization strategy. The limitations of using these methods include the side effects of hyperemia-induced agents, additional costs, and vulnerability to microvascular resistance. FFR is related both to the degree of a stenotic coronary artery and to its subtended myocardial territory. Coronary Artery Tree Description and Lesion Evaluation (CatLet) score (also known as Hexu) is a product of the degree of a stenosis and the weighting of the affected coronary artery (myocardial territory). Hence, we hypothesized that the CatLet score could predict hemodynamically significant coronary stenosis. Methods: We retrospectively enrolled consecutive patients with stable coronary artery disease. They attended Sichuan Science City Hospital with at least one lesion of 50-90% diameter stenosis in a coronary artery of 2 mm or larger. FFR measurement was obtained during invasive coronary angiography. The CatLet score was obtained by multiplying a fixed value of 2.0 (for non-occlusive lesions) and the weight of the affected coronary artery. The primary endpoint was the CatLet score's diagnostic accuracy in identifying hemodynamically significant coronary stenosis, with a pressure wire FFR of ≤0.80 being used as reference. Results: We analyzed the FFR and CatLet scores from 206 vessels in 175 patients with stable coronary disease and intermediate coronary lesions. The per-vessel analysis revealed an overall good correlation between the CatLet score and the FFR [r=-0.61; 95% confidence interval (95% CI): -0.69 to -0.52; P<0.01]. We also noted a significant CatLet score-FFR correlation for each of the left anterior descending artery (LAD), left circumflex (LCX), and right coronary artery (RCA). With a CatLet score ≥10 as a predictor of FFR ≤0.80, the overall diagnostic accuracy included a sensitivity of 78.80% (95% CI: 67.00-87.90%), a specificity of 85.00% (95% CI: 78.00-90.50%), a positive likelihood ratio of 5.25, a negative likelihood ratio of 0.25, and an area under the curve of 0.90 (95% CI: 0.85-0.94). Equivalent vessel-specific results were also achieved for each of the LAD, LCX, and RCA. Conclusions: The CatLet score, solely based on visual estimation of the results of coronary angiography, demonstrated good diagnostic performance with respect to myocardial ischemia. Its clinical values in guiding revascularization warrant further investigation.

Silicon nanoparticles in sustainable agriculture: synthesis, absorption, and plant stress alleviation.

Silicon (Si) is a widely recognized beneficial element in plants. With the emergence of nanotechnology in agriculture, silicon nanoparticles (SiNPs) demonstrate promising applicability in sustainable agriculture. Particularly, the application of SiNPs has proven to be a high-efficiency and cost-effective strategy for protecting plant against various biotic and abiotic stresses such as insect pests, pathogen diseases, metal stress, drought stress, and salt stress. To date, rapid progress has been made in unveiling the multiple functions and related mechanisms of SiNPs in promoting the sustainability of agricultural production in the recent decade, while a comprehensive summary is still lacking. Here, the review provides an up-to-date overview of the synthesis, uptake and translocation, and application of SiNPs in alleviating stresses aiming for the reasonable usage of SiNPs in nano-enabled agriculture. The major points are listed as following: (1) SiNPs can be synthesized by using physical, chemical, and biological (green synthesis) approaches, while green synthesis using agricultural wastes as raw materials is more suitable for large-scale production and recycling agriculture. (2) The uptake and translocation of SiNPs in plants differs significantly from that of Si, which is determined by plant factors and the properties of SiNPs. (3) Under stressful conditions, SiNPs can regulate plant stress acclimation at morphological, physiological, and molecular levels as growth stimulator; as well as deliver pesticides and plant growth regulating chemicals as nanocarrier, thereby enhancing plant growth and yield. (4) Several key issues deserve further investigation including effective approaches of SiNPs synthesis and modification, molecular basis of SiNPs-induced plant stress resistance, and systematic effects of SiNPs on agricultural ecosystem.

How to effectively achieve air pollutant reduction and carbon mitigation in China's industrial sector? A study based on decomposition analysis and scenario simulation.

Reducing air pollutant and carbon emissions in the industrial sector is crucial for the ecological civilization construction in China. In this study, we first employ the generalized Divisia index method to analyze the driving factors of industrial CO2 and SO2 emissions, incorporating fixed asset investment and R&D input. The key sub-sectors that exert significant impact on emissions of the whole industrial sector are identified. And then, scenario analysis and Monte Carlo simulation are utilized to predict future trends and potential for reducing CO2 and SO2 emissions. Furthermore, the carbon peaking time of the industrial sub-sectors is investigated. The results indicate that fixed asset investment and R&D input both have played positive roles in CO2 and SO2 emissions. Emission reduction is mainly driven by investment emission intensity, output emission intensity, and R&D emission intensity. Sub-sectors S09, S10, S11, S12, and S18 present substantial potential for reducing air pollutant and carbon emissions. Although SO2 emissions from the industrial sector are projected to decrease in the future, the peak of CO2 emissions have not been reached. The carbon peak time for the whole industrial sector is predicted in 2025, with the peak of 7892.33 Mt. The five key sub-sectors are anticipated to reach the respective carbon emission peaks at different times. Therefore, to effectively implement industrial air pollutant and carbon reduction, the role of fixed asset investment and R&D input should be fully utilized, and high-energy consumption and high-emission sub-sectors should be prioritized for action.

Tuneable Efficient White Emission of Sb3+/Mn2+ Co-Doped Lead-Free Perovskites for Single-Component White Light-Emitting Diodes.

Inorganic lead-free perovskite nanocrystals (NCs) with broadband self-trapped exciton (STEs) emission and low toxicity have shown enormous application prospects in the field of display and lighting. However, white light-emitting diodes (WLEDs) based on a single-component material with high photoluminescence quantum yield (PLQY) remain challenging. Here, we demonstrate a novel codoping strategy by introducing Sb3+/Mn2+ ions to achieve the tuneable dual emission in lead-free perovskite Cs3InCl6 NCs. The PLQY increases to 59.64% after doping with Sb3+. The codoped Cs3InCl6 NCs exhibit efficient white light emission due to the energy transfer channel from STEs to Mn2+ ions with PLQY of 51.38%. Density functional theory (DFT) calculations have been used to verify deeply the effects of Sb3+/Mn2+ doping. WLEDs based on Sb3+/Mn2+-codoped Cs3InCl6 NCs are explored with color rendering index of 85.5 and color coordinate of (0.398, 0.445), which have been successfully applied as photodetector lighting sources. This work provides a new perspective for designing novel lead-free perovskites to achieve single-component WLEDs.

Systematic optimization and evaluation of culture conditions for the construction of circulating tumor cell clusters using breast cancer cell lines.

BACKGROUND: Circulating tumor cell (CTC) clusters play a critical role in carcinoma metastasis. However, the rarity of CTC clusters and the limitations of capture techniques have retarded the research progress. In vitro CTC clusters model can help to further understand the biological properties of CTC clusters and their clinical significance. Therefore, it is necessary to establish reliable in vitro methodological models to form CTC clusters whose biological characteristics are very similar to clinical CTC clusters. METHODS: The assays of immunofluorescence, transmission electron microscopy, EdU incorporation, cell adhension and microfluidic chips were used. The experimental metastasis model in mice was used. RESULTS: We systematically optimized the culture methods to form in vitro CTC clusters model, and more importantly, evaluated it with reference to the biological capabilities of reported clinical CTC clusters. In vitro CTC clusters exhibited a high degree of similarity to the reported pathological characteristics of CTC clusters isolated from patients at different stages of tumor metastasis, including the appearance morphology, size, adhesive and tight junctions-associated proteins, and other indicators of CTC clusters. Furthermore, in vivo experiments also demonstrated that the CTC clusters had an enhanced ability to grow and metastasize compared to single CTC. CONCLUSIONS: The study provides a reliable model to help to obtain comparatively stable and qualified CTC clusters in vitro, propelling the studies on tumor metastasis.

A new method for unmanned aerial vehicle path planning in complex environments.

To solve the problems of UAV path planning, such as low search efficiency, uneven path, and inability to adapt to unknown environments, this paper proposes A double-layer optimization A* and dynamic window method for UAV path planning. Firstly, the neighboring node clip-off rule is defined to optimize the node expansion mode of the A* algorithm, and the obstacle coverage model is designed to dynamically adjust the heurizing function of the A* algorithm to improve the path search efficiency. Then, the Bresenham algorithm is adopted for collision detection and critical path nodes are extracted to significantly reduce the number of path turning points. Secondly, a new tracking index is proposed to optimize the evaluation function of the dynamic window method to make the local path fit the global path further. By detecting the dangerous distance, the dynamic adaptive method of evaluation function weight is designed to improve the fixed weight of the dynamic window method. Finally, the key turning point of optimizing the A* algorithm is taken as the temporary target point to improve the DWA algorithm, and the local part follows the global part, and the fusion of the two algorithms is realized. Simulation results show that the proposed method can significantly improve the efficiency and smoothness of mobile robot path planning, enhance the real-time obstacle avoidance and adaptive ability of unknown environments, and better meet the requirements of complex planning tasks.

PVDF/ZnO piezoelectric nanofibers designed for monitoring of internal micro-pressure.

Organic piezoelectric materials are emerging as integral components in the development of advanced implantable self-powered sensors for the next generation. Despite their promising applications, a key limitation lies in their reduced mechanical force-to-electricity conversion efficiency. In this study, we present a breakthrough in the fabrication of soft poly(vinylidene fluoride) (PVDF) organic electrospun piezoelectric nanofibers (OEPNs) with exceptional piezoelectric performance achieved through the incorporation of zinc oxide nanorods (ZnO NR). The inclusion of ZnO NR proved instrumental in augmenting the nanocrystallization of PVDF organic electrospun piezoelectric nanofibers (OEPNs), leading to a highly efficient crystal phase transformation from the α phase to the ß/γ phase, serving as superior piezoelectric working dipoles. The resulting PVDF/ZnO NR OEPNs exhibited unparalleled piezoelectric output voltage and current density, particularly noteworthy under a micro-pressure of 1 kPa and a low frequency of 1.5 Hz. Utilizing the obtained PVDF/ZnO NR OEPNs as the piezoelectric working element, we engineered a soft self-powered micro-pressure sensor. This sensor was implanted simultaneously on the cardiovascular walls of the heart and femoral artery in pigs. The sensor demonstrated precise monitoring and recording capabilities for micro-pressure changes during various physiological states, spanning from wakefulness to coma, euthanasia, and notably, the formation of cardiac thrombus. These findings underscore the immense potential of the implantable self-powered sensor for the assessment and diagnosis of pressure-related cardiovascular diseases, such as thrombus and atherosclerosis, during the postoperative recovery phase. This innovative technology offers valuable insights into the dynamic physiological states, paving the way for enhanced postoperative care and management of cardiovascular conditions.

Thread-structural microneedles loaded with engineered exosomes for annulus fibrosus repair by regulating mitophagy recovery and extracellular matrix homeostasis.

Low back pain is among the most grave public health concerns worldwide and the major clinical manifestation of intervertebral disc degeneration (IVDD). The destruction of annulus fibrosus (AF) is the primary cause of IVDD. A sustainable and stable treatment system for IVDD is lacking because of the special organizational structure and low nutrient supply of AF. We here found that IVDD results in the impaired mitochondrial function of AF tissue, and mitochondrial autophagy (mitophagy) plays a protective role in this process. We therefore reported a thread-structural microneedle (T-MN) matching the ring structure of AF. Based on the adsorption effect of laminin, our T-MN could load with bone marrow mesenchymal stem cell-derived exosomes to envelope the regulating mitophagy microRNA (miRNA 378), named as T-MN@EXO@miR-378. In general, we offered in situ locking in the defect site of AF to prevent nucleus pulposus leakage and promoted AF repair. The design of the thread structure was aimed at bionically matching the layered AF structure, thereby providing stronger adhesion. The T-MN@EXO@miR-378 effectively attached to AF and slowly released therapeutic engineered exosomes, and prevented IVDD progression by restoring mitophagy, promoting AF cell proliferation and migration, and inhibiting the pathological remodeling of the extracellular matrix. This functional system can be used as an excellent tool for sustained drug release and has a certain prospect in substituting the conventional treatment of IVDD.

The effect and mechanism of volatile oil emulsion from leaves of Clausena lansium (Lour.) Skeels on Staphylococcus aureus in vitro.

This study aimed to develop a suitable dosage form of volatile oil from wampee leaves and to explore its antibacterial mechanism in vitro. The chemical composition of the volatile oil from wampee leaves was determined by gas chromatography-mass spectrometry (GC-MS). Different microemulsion ratios were tested and their stabilities were investigated to determine the optimal ratio. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the wampee leaves volatile oil emulsion (WVOE) against Salmonella typhimurium (S. typhimurium) and Staphylococcus aureus (S. aureus) were determined using double-dilution and plate-counting methods, respectively. Morphological changes in these two bacteria were observed using scanning electron microscopy. Death, ultrastructural morphology, and biofilm formation were also assessed for S. aureus. Finally, we established an S. aureus-infected Lewis lung carcinoma (LLC) cell model to evaluate the protective effects of the volatile oil emulsion and the associated mechanisms. The volatile oil extracted from wampee leaves contained 37 compounds, of which 96.49% were aromatic hydrocarbons, terpenoids, and their oxygen-containing derivatives. The emulsion was most stable at 1:1 in the oil phase and 1:9 in the water phase. WVOE had poor antibacterial activity against S. typhimurium, but the MIC and MBC against S. aureus were 312.5 and 2,500 µg/mL, respectively. S. aureus survival rates were 84.6%, 14.5%, and 12.8% in the 1/2, 1, and 4 × MIC groups, respectively, compared with 97.2% in the control group. S. typhimurium survival was not affected by WVOE treatment. WVOE administration induced cavity formation and abnormal binary fission, and significantly inhibited biofilm formation in S. aureus cells. The WVOE notably reduced the number of S. aureus and inhibited TLR4, NLRP3, NF-κB, IL-6, IL-18, and TNF-α gene expression in S. aureus-infected LLC cells. The WVOE had a significant inhibitory effect on S. aureus and altered its cell membrane permeability. Moreover, it alleviated inflammation by inhibiting the NF-κB-NLRP3 pathway in S. aureus-infected LLC cells.

Brigatinib, a newly discovered AXL inhibitor, suppresses AXL-mediated acquired resistance to osimertinib in EGFR-mutated non-small cell lung cancer.

In addition to the classical resistance mechanisms, receptor tyrosine-protein kinase AXL is a main mechanism of resistance to third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) osimertinib in EGFR-mutated non-small cell lung cancer (NSCLC). Developing an effective AXL inhibitor is important to sensitize osimertinib in clinical application. In this study we assessed the efficacy of brigatinib, a second-generation of anaplastic lymphoma kinase (ALK)-TKI, as a novel AXL inhibitor, in overcoming acquired resistance to osimertinib induced by AXL activation. We established an AXL-overexpression NSCLC cell line and conducted high-throughput screening of a small molecule chemical library containing 510 anti-tumor drugs. We found that brigatinib potently inhibited AXL expression, and that brigatinib (0.5 µM) significantly enhanced the anti-tumor efficacy of osimertinib (1 µM) in AXL-mediated osimertinib-resistant NSCLC cell lines in vitro. We demonstrated that brigatinib had a potential ability to bind AXL kinase protein and further inhibit its downstream pathways in NSCLC cell lines. Furthermore, we revealed that brigatinib might decrease AXL expression through increasing K48-linked ubiquitination of AXL and promoting AXL degradation in HCC827OR cells and PC-9OR cells. In AXL-high expression osimertinib-resistant PC-9OR and HCC827OR cells derived xenograft mouse models, administration of osimertinib (10 mg·kg-1·d-1) alone for 3 weeks had no effect, and administration of brigatinib (25 mg·kg-1·d-1) alone caused a minor inhibition on the tumor growth; whereas combination of osimertinib and brigatinib caused marked tumor shrinkages. We concluded that brigatinib may be a promising clinical strategy for enhancing osimertinib efficacy in AXL-mediated osimertinib-resistant NSCLC patients.

A 3D-printed microhemispherical shell resonator with electrostatic tuning for a Coriolis vibratory gyroscope.

The emergence of microhemispherical resonant gyroscopes, which integrate the advantages of exceptional stability and long lifetime with miniaturization, has afforded new possibilities for the development of whole-angle gyroscopes. However, existing methods used for manufacturing microhemispherical resonant gyroscopes based on MEMS technology face the primary drawback of intricate and costly processing. Here, we report the design, fabrication, and characterization of the first 3D-printable microhemispherical shell resonator for a Coriolis vibrating gyroscope. We remarkably achieve fabrication in just two steps bypassing the dozen or so steps required in traditional micromachining. By utilizing the intricate shaping capability and ultrahigh precision offered by projection microstereolithography, we fabricate 3D high-aspect-ratio resonant structures and controllable capacitive air gaps, both of which are extremely difficult to obtain via MEMS technology. In addition, the resonance frequency of the fabricated resonators can be tuned by electrostatic forces, and the fabricated resonators exhibit a higher quality factor in air than do typical MEMS microhemispherical resonators. This work demonstrates the feasibility of rapidly batch-manufacturing microhemispherical shell resonators, paving the way for the development of microhemispherical resonator gyroscopes for portable inertial navigation. Moreover, this particular design concept could be further applied to increase uptake of resonator tools in the MEMS community.

Directionally Illuminated Autostereoscopy with Seamless Viewpoints for Multi-Viewers.

Autostereoscopy is usually perceived at finite viewpoints that result from the separated pixel array of a display system. With directionally illuminated autostereoscopy, the separation of the illumination channel from the image channel provides extra flexibility in optimizing the performance of autostereoscopy. This work demonstrates that by taking advantage of illumination freedom, seamless viewpoints in the sweet viewing region, where the ghosting does not cause significant discomfort, are realized. This realization is based on illuminating the screen with a polyline array of light emitting diodes (LEDs), and continuous viewpoints are generated through independent variation in the radiance of each individual LED column. This new method is implemented in the directionally illuminated display for both single and multiple viewers, proving its effectiveness as a valuable technique for achieving a high-quality and high-resolution autostereoscopic display with seamless viewpoints.

68Ga-FAPI-04 PET/CT in Non-Small Cell Lung Cancer: Accurate Evaluation of Lymph Node Metastasis and Correlation with Fibroblast Activation Protein Expression.

Fibroblast activation protein (FAP) is a promising diagnostic and therapeutic target in various solid tumors. This study aimed to assess the diagnostic efficiency of 68Ga-labeled FAP inhibitor (FAPI)-04 PET/CT for detecting lymph node metastasis in non-small cell lung cancer (NSCLC) and to investigate the correlation between tumor 68Ga-FAPI-04 uptake and FAP expression. Methods: We retrospectively enrolled 136 participants with suspected or biopsy-confirmed NSCLC who underwent 68Ga-FAPI-04 PET/CT for initial staging. The diagnostic performance of 68Ga-FAPI-04 for the detection of NSCLC was evaluated. The final histopathology or typical imaging features were used as the reference standard. The SUVmax and SUVmean, 68Ga-FAPI-avid tumor volume (FTV), and total lesion FAP expression (TLF) were measured and calculated. FAP immunostaining of tissue specimens was performed. The correlation between 68Ga-FAPI-04 uptake and FAP expression was assessed using the Spearman correlation coefficient. Results: Ninety-one participants (median age, 65 y [interquartile range, 58-70 y]; 69 men) with NSCLC were finally analyzed. In lesion-based analysis, the diagnostic sensitivity and positive predictive value of 68Ga-FAPI-04 PET/CT for detection of the primary tumor were 96.70% (88/91) and 100% (88/88), respectively. In station-based analysis, the diagnostic sensitivity, specificity, and accuracy for the detection of lymph node metastasis were 72.00% (18/25), 93.10% (108/116), and 89.36% (126/141), respectively. Tumor 68Ga-FAPI-04 uptake (SUVmax, SUVmean, FTV, and TLF) correlated positively with FAP expression (r = 0.470, 0.477, 0.582, and 0.608, respectively; all P ≤ 0.001). The volume parameters FTV and TLF correlated strongly with FAP expression in 31 surgical specimens (r = 0.700 and 0.770, respectively; both P < 0.001). Conclusion: 68Ga-FAPI-04 PET/CT had excellent diagnostic efficiency for detecting lymph node metastasis, and 68Ga-FAPI-04 uptake showed a close association with FAP expression in participants with NSCLC.

Floral resource partitioning of coexisting bumble bees: Distinguishing species-, colony-, and individual-level effects.

Resource partitioning is considered a key factor in alleviating competitive interactions, enabling coexistence among consumer species. However, most studies have focused on resource partitioning between species, ignoring the potentially critical role of intraspecific variation in resource use. We investigated floral resource partitioning across species, colonies, and individuals in a species-rich bumblebee community in the diversification center of bumblebees. We used a total of 10,598 bumblebees belonging to 13 species across 5 years in the Hengduan Mountains of southwest China. First, we evaluated the influence of a comprehensive set of floral traits, including both those related to attractiveness (flower color and shape) and rewards (pollen, sugar ratio, nectar volume, sugar concentration, and amino acid content) on resource partitioning at the species level in bumblebee-plant networks. Then, we explored intraspecific resource partitioning on the colony and individual levels. Our results suggest that bumblebee species differ substantially in their use of the available floral resources, and that this mainly depends on flower attractiveness (floral color and shape). Interestingly, we also detected floral resource partitioning at the colony level within all commonest bumblebee species evaluated. In general, floral resource partitioning between bumblebee individuals decreased with species- and individual-level variation in body size (intertegular span). These results suggest that bumblebee species may coexist via the flexibility in their preferences for specific floral traits, which filters up to support the co-occurrence of high numbers of species and individuals in this global hotspot of species richness.

Pyoluteorin regulates the biosynthesis of 2,4-DAPG through the TetR family transcription factor PhlH in Pseudomonas protegens Pf-5.

Soil and rhizosphere bacteria act as a rich source of secondary metabolites, effectively fighting against a diverse array of pathogens. Certain Pseudomonas species harbor biosynthetic gene clusters for producing both pyoluteorin and 2,4-diacetylphloroglucinol (2,4-DAPG), which are polyketides that exhibit highly similar antimicrobial spectrum against bacteria and fungi or oomycete. A complex cross talk exists between pyoluteorin and 2,4-DAPG biosynthesis, and production of 2,4-DAPG was strongly repressed by pyoluteorin, yet the underlying mechanism is still elusive. In this study, we find that the TetR family transcription factor PhlH is involved in the cross talk between pyoluteorin and 2,4-DAPG biosynthesis. PhlH binds to a palindromic sequence within the promoter of phlG (PphlG), which encodes a C-C bond hydrolase responsible for degrading 2,4-DAPG. As a signaling molecule, pyoluteorin disrupts the PhlH-PphlG complex by binding to PhlH, leading to decreased levels of 2,4-DAPG. Proteomics data suggest that pyoluteorin regulates multiple physiological processes including fatty acid biosynthesis and transportation of taurine, siderophore, and amino acids. Our work not only reveals a novel mechanism of cross talk between pyoluteorin and 2,4-DAPG biosynthesis, but also highlights pyoluteorin's role as a messenger in the complex communication network of Pseudomonas.IMPORTANCEAntibiosis serves as a crucial defense mechanism for microbes against invasive bacteria and resource competition. These bacteria typically orchestrate the production of multiple antibiotics in a coordinated fashion, wherein the synthesis of one antibiotic inhibits the generation of another. This strategic coordination allows the bacterium to focus its resources on producing the most advantageous antibiotic under specific circumstances. However, the underlying mechanisms of distinct antibiotic production in bacterial cells remain largely elusive. In this study, we reveal that the TetR family transcription factor PhlH detects the secondary metabolite pyoluteorin and mediates the cross talk between pyoluteorin and 2,4-DAPG biosynthesis in the biocontrol strain Pseudomonas protegens Pf-5. These findings hold promise for future research, potentially informing the manipulation of these systems to enhance the effectiveness of biocontrol agents.

Risk factors for cognitive impairment in patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) patients have been found to be at risk of concurrent cognitive dysfunction in previous studies, which has now become an important public health issue of widespread concern. AIM: To investigate the risk factors for concurrent cognitive dysfunction in patients with CKD. METHODS: This is a prospective cohort study conducted among patients with CKD between October 2021 and March 2023. A questionnaire was formulated by literature review and expert consultation and included questions about age, sex, education level, per capita monthly household income, marital status, living condition, payment method, and hypertension. RESULTS: Logistic regression analysis showed that patients aged 60-79 years [odds ratio (OR) = 1.561, P = 0.015] and ≥ 80 years (OR = 1.760, P = 0.013), participants with middle to high school education (OR = 0.820, P = 0.027), divorced or widowed individuals (OR = 1.37, P = 0.032), self-funded patients (OR = 2.368, P = 0.008), and patients with hypertension (OR = 2.011, P = 0.041) had a higher risk of cognitive impairment. The risk of cognitive impairment was lower for those with a college degree (OR = 0.435, P = 0.034) and married individuals. CONCLUSION: The risk factors affecting cognitive dysfunction are age, 60-79 years and ≥ 80 years; education, primary school education or less; marital status, divorced or widowed; payment method, self-funded; hypertension; and CKD.

Electroconvulsive therapy regulates brain connectome dynamics in patients with major depressive disorder.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for patients with major depressive disorder (MDD), but its underlying neural mechanisms remain largely unknown. The aim of this study was to identify changes in brain connectome dynamics after ECT in MDD and to explore their associations with treatment outcome. METHODS: We collected longitudinal resting-state fMRI data from 80 MDD patients (50 with suicidal ideation and 30 without; SI and NSI, respectively) before and after ECT and 37 age- and sex-matched healthy controls. A multilayer network model was used to assess modular switching over time in functional connectomes. Support vector regression was used to assess whether pre-ECT network dynamics could predict treatment response in terms of symptom severity. RESULTS: At baseline, MDD patients had lower global modularity and higher modular variability in functional connectomes compared to controls. Network modularity increased and network variability decreased after ECT in MDD patients, predominantly located in the default mode and somatomotor networks. Moreover, ECT was associated with decreased modular variability in the left dorsal anterior cingulate cortex of MDD-SI, but not MDD-NSI patients, and pre-ECT modular variability could significantly predict symptom improvement in the MDD-SI group, but not in the MDD-NSI group. CONCLUSIONS: We highlight ECT-induced changes in MDD brain network dynamics and their predictive value for treatment outcome, particularly in patients with suicidal ideation. This study advances our understanding of the neural mechanisms of ECT from a dynamic brain network perspective and suggests potential prognostic biomarkers for predicting ECT efficacy in patients with MDD.