Soft Polyethylene Glycol Hydrogels Support Human PSC Pluripotency and Morphogenesis.

Lumenogenesis within the epiblast represents a critical step in early human development, priming the embryo for future specification and patterning events. However, little is known about the specific mechanisms that drive this process due to the inability to study the early embryo in vivo. While human pluripotent stem cell (hPSC)-based models recapitulate many aspects of the human epiblast, most approaches for generating these 3D structures rely on ill-defined, reconstituted basement membrane matrices. Here, we designed synthetic, nonadhesive polyethylene glycol (PEG) hydrogel matrices to better understand the role of matrix mechanical cues in iPSC morphogenesis, specifically elastic modulus. First, we identified a narrow range of hydrogel moduli that were conducive to the hPSC viability, pluripotency, and differentiation. We then used this platform to investigate the effects of the hydrogel modulus on lumenogenesis, finding that matrices of intermediate stiffness yielded the most epiblast-like aggregates. Conversely, stiffer matrices impeded lumen formation and apico-basal polarization, while the softest matrices yielded polarized but aberrant structures. Our approach offers a simple, modular platform for modeling the human epiblast and investigating the role of matrix cues in its morphogenesis.

Remimazolam has similar anesthetic effect and superior safety compared to propofol in elderly patients: A meta-analysis of randomized controlled trials.

BACKGROUND: The superiority between remimazolam and propofol for anesthesia is controversial in elderly patients (≥60 years). This meta-analysis aimed to systematically compare anesthetic effect and safety profile between remimazolam and propofol in elderly patients under any surgery. METHODS: Cochrane Library, Web of Science, and PubMed were searched until December 25, 2023 for relevant randomized controlled trials. RESULTS: Ten studies with 806 patients receiving remimazolam (experimental group) and 813 patients receiving propofol (control group) were included. Time to loss of consciousness [standard mean difference (SMD) (95% confidence interval (CI): 1.347 (-0.362, 3.055), p = 0.122] and recovery time [SMD (95% CI): -0.022 (-0.300, 0.257), p = 0.879] were similar between experimental and control groups. Mean arterial pressure at baseline minus 1 min after induction [SMD (95% CI): -1.800 (-3.250, -0.349), p = 0.015], heart rate at baseline minus 1 min after induction [SMD (95% CI): -1.041 (-1.537, -0.545), p < 0.001], incidences of hypoxemia [relative risk (RR) (95% CI): 0.247 (0.138, 0.444), p < 0.001], respiratory depression [RR (95% CI): 0.458 (0.300, 0.700), p < 0.001], bradycardia [RR (95% CI): 0.409 (0.176, 0.954), p = 0.043], hypotension [RR (95% CI): 0.415 (0.241, 0.714), p = 0.007], and injection pain [RR (95% CI): 0.172 (0.113, 0.263), p < 0.001] were lower in the experimental group compared to the control group. Postoperative nausea and vomiting was not different between groups [RR (95% CI): 1.194 (0.829, 1.718), p = 0.341]. Moreover, this meta-analysis displayed a low risk of bias, minimal publication bias, and good robustness. CONCLUSION: Remimazolam shows comparative anesthetic effect and better safety profile than propofol in elderly patients under any surgery.

Stacking engineering induced Z-scheme MoSSe/WSSe heterostructure for photocatalytic water splitting.

Stacking engineering is a popular method to tune the performance of two-dimensional materials for advanced applications. In this work, Jansu MoSSe and WSSe monolayers are constructed as a van der Waals (vdWs) heterostructure by different stacking configurations. Using first-principle calculations, all the relaxed stacking configurations of the MoSSe/WSSe heterostructure present semiconductor properties while the direct type-II band structure can be obtained. Importantly, the Z-scheme charge transfer mode also can be addressed by band alignment, which shows the MoSSe/WSSe heterostructure is an efficient potential photocatalyst for water splitting. In addition, the built-in electric field of the MoSSe/WSSe vdWs heterostructure can be enhanced by the S-Se interface due to further asymmetric structures, which also results in considerable charge transfer comparing with the MoSSe/WSSe vdWs heterostructure built by the S-S interface. Furthermore, the excellent optical performances of the MoSSe/WSSe heterostructure with different stacking configurations are obtained. Our results provide a theoretical guidance for the design and control of the two-dimensional heterostructure as photocatalysts through structural stacking.

Comparison of staining quality between rapid and routine hematoxylin and eosin staining of frozen breast tissue sections: an observational study.

OBJECTIVE: To compare the staining quality between rapid hematoxylin and eosin (H&E) staining and routine H&E staining of frozen breast tissue sections. METHODS: In this cross-sectional observational study, 120 frozen breast tissue sections were randomly assigned to rapid or routine H&E staining (n = 60 per group). Rapid H&E staining used a 7:1 mixture of modified Gill's hematoxylin and alcohol-soluble 1% eosin Y. The staining quality of each section was evaluated and scored. A score of >7 was considered excellent, a score of 6 to 7 good, and a score of ≤5 poor. RESULTS: The staining time for rapid staining was approximately 3 minutes, whereas that of routine staining was approximately 12 minutes. There were no significant differences in the staining quality scores or proportions of sections in each grade between the two staining methods. The proportions of sections that were classified as excellent or good were 96.7% and 98.3% for rapid and routine staining, respectively. CONCLUSIONS: In frozen breast tissue sections, rapid H&E staining may provide staining quality that is comparable to that of routine staining, while markedly reducing the staining time.

Taxonomic identification, phenol biodegradation and soil remediation of the strain Rhodococcus sacchari sp. nov. Z13T.

Phenols are highly toxic chemicals that are extensively used in industry and produce large amounts of emissions. Notably, phenols released into the soil are highly persistent, causing long-term harm to human health and the environment. In this study, a gram-positive, aerobic, and rod-shaped bacterial strain, Z13T, with efficient phenol degradation ability, was isolated from the soil of sugarcane fields. Based on the physiological properties and genomic features, strain Z13T is considered as a novel species of the genus Rhodococcus, for which the name Rhodococcus sacchari sp. nov. is proposed. The type strain is Z13T (= CCTCC AB 2022327T = JCM 35797T). This strain can use phenol as its sole carbon source. Z13T was able to completely degrade 1200 mg/L phenol within 20 h; the maximum specific growth rate was µmax = 0.93174 h-1, and the maximum specific degradation rate was qmax = 0.47405 h-1. Based on whole-genome sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, strain Z13T contains a series of phenol degradation genes, including dmpP, CatA, dmpB, pcaG, and pcaH, and can metabolize aromatic compounds. Moreover, the potential of strain Z13T for soil remediation was investigated by introducing Z13T into simulated phenol-contaminated soil, and the soil microbial diversity was analyzed. The results showed that 100% of the phenol in the soil was removed within 7.5 d. Furthermore, microbial diversity analysis revealed an increase in the relative species richness of Oceanobacillus, Chungangia, and Bacillus.

Calcium regulates the interactions between dissolved organic matter and planktonic bacteria in Erhai Lake, Yunnan Province, China.

In recent years, the global carbon cycle has garnered significant research attention. However, details of the intricate relationship between planktonic bacteria, hydrochemistry, and dissolved organic matter (DOM) in inland waters remain unclear, especially their effects on lake carbon sequestration. In this study, we analyzed 16S rRNA, chromophoric dissolved organic matter (CDOM), and inorganic nutrients in Erhai Lake, Yunnan Province, China. The results revealed that allochthonous DOM (C3) significantly regulated the microbial community, and that autochthonous DOM, generated via microbial mineralization (C2), was not preferred as a food source by lake bacteria, and neither was allochthonous DOM after microbial mineralization (C4). Specifically, the correlation between the fluorescence index and functional genes (FAPRPTAX) showed that the degree of utilization of DOM was a critical factor in regulating planktonic bacteria associated with the carbon cycle. Further examination of the correlation between environmental factors and planktonic bacteria revealed that Ca2+ had a regulatory influence on the community structure of planktonic bacteria, particularly those linked to the carbon cycle. Consequently, the utilization strategy of DOM by planktonic bacteria was also determined by elevated Ca2+ levels. This in turn influenced the development of specific recalcitrant autochthonous DOM within the high Ca2+ environment of Erhai Lake. These findings are significant for the exploration of the stability of DOM within karst aquatic ecosystems, offering a new perspective for the investigation of terrestrial carbon sinks.

Cross-sectional study of association between caries and fluoridated water among third-grade students in Pennsylvania.

BACKGROUND: Caries is the most common chronic disease among children. In Pennsylvania, a comprehensive oral health Basic Screening Survey and assessment of the association between caries and community water fluoridation (CWF) among children have not been conducted. METHODS: From 2021 through 2022, the first Basic Screening Survey was conducted among third-grade students in Pennsylvania. Oral health and demographic data were collected. CWF data were provided by the Pennsylvania Department of Environmental Protection. The relative risk of developing caries in association with CWF was assessed using the GENMOD procedure in SAS, Version 9.4 (SAS Institute) in this cross-sectional study. RESULTS: Caries prevalence was 59.7% among 4,120 screened students. Participation in the free or reduced lunch program and CWF were each significantly associated with risk of developing caries after adjustment for age, sex, and race and ethnicity. The risk of developing caries was 33% higher among students who participated in the free or reduced lunch program than those who did not participate (relative risk, 1.33; 95% CI, 1.24 to 1.42). Students with the highest CWF coverage had a nearly 16% lower risk of developing caries than those without CWF coverage (relative risk, 0.84; 95% CI, 0.75 to 0.94). CONCLUSIONS: CWF was significantly associated with a reduced risk of developing caries. Efforts are needed to increase CWF coverage, along with promotion of oral health education and healthy dietary habits among Pennsylvania children. PRACTICAL IMPLICATIONS: Increasing CWF coverage will reduce caries burden among Pennsylvania children. Although Pennsylvania has no state laws to regulate CWF, these findings are persuasive for local municipalities to consider expanding CWF coverage.

Angular Isotonic Loss Guided Multi-Layer Integration for Few-Shot Fine-Grained Image Classification.

Recent research on few-shot fine-grained image classification (FSFG) has predominantly focused on extracting discriminative features. The limited attention paid to the role of loss functions has resulted in weaker preservation of similarity relationships between query and support instances, thereby potentially limiting the performance of FSFG. In this regard, we analyze the limitations of widely adopted cross-entropy loss and introduce a novel Angular ISotonic (AIS) loss. The AIS loss introduces an angular margin to constrain the prototypes to maintain a certain distance from a pre-set threshold. It guides the model to converge more stably, learn clearer boundaries among highly similar classes, and achieve higher accuracy faster with limited instances. Moreover, to better accommodate the feature requirements of the AIS loss and fully exploit its potential in FSFG, we propose a Multi-Layer Integration (MLI) network that captures object features from multiple perspectives to provide more comprehensive and informative representations of the input images. Extensive experiments demonstrate the effectiveness of our proposed method on four standard fine-grained benchmarks. Codes are available at: https://github.com/Legenddddd/AIS-MLI.

Atom Pairing Enhances Sulfur Resistance in Low-Temperature SCR via Upshifting the Lowest Unoccupied States of Cerium.

Environmentally benign cerium-based catalysts are promising alternatives to toxic vanadium-based catalysts for controlling NOx emissions via selective catalytic reduction (SCR), but conventional cerium-based catalysts unavoidably suffer from SO2 poisoning in low-temperature SCR. We develop a strongly sulfur-resistant Ce1+1/TiO2 catalyst by spatially confining Ce atom pairs to different anchoring sites of anatase TiO2(001) surfaces. Experimental results combined with theoretical calculations demonstrate that strong electronic interactions between the paired Ce atoms upshift the lowest unoccupied states to an energy level higher than the highest occupied molecular orbital (HOMO) of SO2 so as to be catalytically inert in SO2 oxidation but slightly lower than HOMO of NH3 so that Ce1+1/TiO2 has desired ability toward NH3 activation required for SCR. Hence, Ce1+1/TiO2 shows higher SCR activity and excellent stability in the presence of SO2 at low temperatures with respect to supported single Ce atoms. This work provides a general strategy to develop sulfur-resistant catalysts by tuning the electronic states of active sites for low-temperature SCR, which has implications for practical applications with energy-saving requirements.

Design optimization of geometrically confined cardiac organoids enabled by machine learning techniques.

Stem cell organoids are powerful models for studying organ development, disease modeling, drug screening, and regenerative medicine applications. The convergence of organoid technology, tissue engineering, and artificial intelligence (AI) could potentially enhance our understanding of the design principles for organoid engineering. In this study, we utilized micropatterning techniques to create a designer library of 230 cardiac organoids with 7 geometric designs. We employed manifold learning techniques to analyze single organoid heterogeneity based on 10 physiological parameters. We clustered and refined the cardiac organoids based on their functional similarity using unsupervised machine learning approaches, thus elucidating unique functionalities associated with geometric designs. We also highlighted the critical role of calcium transient rising time in distinguishing organoids based on geometric patterns and clustering results. This integration of organoid engineering and machine learning enhances our understanding of structure-function relationships in cardiac organoids, paving the way for more controlled and optimized organoid design.

Identification of clear cell renal cell carcinoma subtypes by integrating radiomics and transcriptomics.

Objective: This study aimed to delineate the clear cell renal cell carcinoma (ccRCC) intrinsic subtypes through unsupervised clustering of radiomics and transcriptomics data and to evaluate their associations with clinicopathological features, prognosis, and molecular characteristics. Methods: Using a retrospective dual-center approach, we gathered transcriptomic and clinical data from ccRCC patients registered in The Cancer Genome Atlas and contrast-enhanced computed tomography images from The Cancer Imaging Archive and local databases. Following the segmentation of images, radiomics feature extraction, and feature preprocessing, we performed unsupervised clustering based on the "CancerSubtypes" package to identify distinct radiotranscriptomic subtypes, which were then correlated with clinical-pathological, prognostic, immune, and molecular characteristics. Results: Clustering identified three subtypes, C1, C2, and C3, each of which displayed unique clinicopathological, prognostic, immune, and molecular distinctions. Notably, subtypes C1 and C3 were associated with poorer survival outcomes than subtype C2. Pathway analysis highlighted immune pathway activation in C1 and metabolic pathway prominence in C2. Gene mutation analysis identified VHL and PBRM1 as the most commonly mutated genes, with more mutated genes observed in the C3 subtype. Despite similar tumor mutation burdens, microsatellite instability, and RNA interference across subtypes, C1 and C3 demonstrated greater tumor immune dysfunction and rejection. In the validation cohort, the various subtypes showed comparable results in terms of clinicopathological features and prognosis to those observed in the training cohort, thus confirming the efficacy of our algorithm. Conclusion: Unsupervised clustering based on radiotranscriptomics can identify the intrinsic subtypes of ccRCC, and radiotranscriptomic subtypes can characterize the prognosis and molecular features of tumors, enabling noninvasive tumor risk stratification.

N/P-doped NiFeV oxide nanosheets with oxygen vacancies as an efficient electrocatalyst for the oxygen evolution reaction.

Plasma treatment as an effective strategy can simultaneously achieve surface modification and heteroatom doping. Here, an N/P-doped NiFeV oxide nanosheet catalyst (N/P-NiFeVO) constructed by Ar/PH3 plasma treatment is used to drive the oxygen evolution reaction (OER). The introduction of V species leads to the formation of an ultrathin ordered nanostructure and exposure of more active sites. Compared to the 2D NiFeV LDH, the prepared N/P-NiFeVO by plasma treatment possesses multiple-valence Fe, V and Ni species, which regulate the intrinsic electronic structure and enable a superior catalytic activity for the OER in alkaline media. Specifically, the N/P-NiFeVO only require an overpotential of 273 mV to drive the current density of 100 mA cm-2. What's more, the electrode can maintain a stable current density in a long-term oxygen evolution reaction (∼120 h) under alkaline conditions. This work provides new insight for the rational design of mixed metal oxides for OER electrocatalysts.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) activates p38 to affect pulmonary fibrosis.

Objective: We aimed to examine whether heparin-binding epidermal growth factor-like growth factor (HB-EGF) affects the lung fibrosis process through the activation of p38 protein in mitogen-activated protein kinases (MAPK) signaling pathway, as well as the expression of downstream inflammatory factors. Methods: The expression levels of HB-EGF, collagen type I (COL-I), and hexokinase 2 (HK2) in peripheral blood mononuclear cells (PBMCs) of patients with connective tissue disease-related interstitial lung disease (CTD-ILD) were examined by qPCR, Western blotting and ELISA. Results: In vitro experiments showed that HB-EGF was increased in almost all subtypes [rheumatoid arthritis (RA), systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIMs)] as well as in all groups (P < 0.05). For embryonic lung fibroblast (A549) cells, the expression levels of HK2 and α-smooth muscle actin (α-SMA) genes were elevated during 0-4 h and then plateaued. Transforming growth factor-ß1 (TGF-ß1) induced fibrosis in human embryonic lung fibroblasts (MRC-5) cells and A549 for a certain period of time, but the degree of induction varied, which may be related to the redifferentiability of cells at different spatial locations. Moreover, HB-EGF at concentrations above 1 ng/ml stimulation increased COL-I expression (P < 0.05), and for α-SMA gene, even 1 ng/ml concentration of HB-EGF had a stimulatory effect, and different concentrations of HB-EGF did activate the expression of p38 in a concentration-dependent manner within a certain concentration range, and by The qPCR results showed that for interleukin 6 (IL-6), an inflammatory factor regulated downstream of p38, the expression was significantly increased in A549 cells compared to control (P < 0.05), but tumor necrosis factor-α (TNF-α) expression was downregulated (P < 0.05), but for interleukin-1ß (IL-1ß) gene, there was no significant difference in A549 cells, and expression was downregulated in MRC-5 cells. Therefore, it is suggested that HB-EGF regulates the expression of inflammatory factors through p38 will be differential across cells. Conclusion: Our study shows that HB-EGF can suppress pulmonary fibrosis through downstream activation of p38/MAPK pathway activity, as well as the expression of various inflammatory factors downstream of it.

Mechanism of action of Sambucus williamsii Hance var. miquelii in the treatment of osteoporosis analyzed by UHPLC-HRMS/MS combined network pharmacology and experimental validation.

Sambucus williamsii Hance var. miquelii(SWH) is a precious wild Chinese herb whose fruit, rhizome, leaves and root bark can be used as medicine. Sambucus Linn has pharmacological effects such as anti-osteoporosis, promoting fracture healing, anti-viral and anti-inflammatory. In this study, the main chemical components of the alcoholic extracts from SWH were rapidly identified by ultra-high performance liquid chromatography-quadrupole orbit trap high-resolution mass spectrometry (UHPLC- HRMS MS), and a total of 42 compounds were characterized from the alcoholic extracts of SWH. The results of network pharmacological validation showed that kaempferol, quercetin, luteolin, isorhamnetin and morroniside were the main active components, and KEGG enrichment demonstrated that SWH mainly affected the signaling pathways such as PI3K-Akt, TNF and FoxO by modulating the related targets such as AKT1, PIK3R1, EGFR, RELA SRC and PTGS2. The molecular docking results showed binding solid activity between the main active components of SWH and the targets. The network pharmacology was validated by establishing an animal model of osteoporosis (OP) in rats by gavage administration of vitamin A acid. The results of the pharmacological experiments showed that SWH could improve the degree of bone loss in the femur of osteoporotic rats, increase the number of trabeculae and decrease trabeculae porosity, up-regulate the Ca and P content in the serum of OP rats, down-regulate the scope of ALP and BGP in the serum, and promote the calcification of the bone matrix, and then exert the anti-OP efficacy. In this study, network pharmacology and pharmacological experiments verified the pharmacological mechanism of SWH in anti-OP rats. This provides a theoretical basis for the research and development of anti-OP drugs and a reference for the application of other traditional Chinese medicines in treating OP diseases.

INDUCED PLURIPOTENT STEM CELL-DERIVED MESENCHYMAL STEM CELLS-DERIVED EXTRACELLULAR VESICLES ATTENUATE LPS-INDUCED LUNG INJURY AND ENDOTOXEMIA IN MICE.

ABSTRACT: Introduction: We hypothesized extracellular vesicles (EVs) from preconditioned human-induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) attenuate LPS-induced acute lung injury (ALI) and endotoxemia. Methods: iMSCs were incubated with cell stimulation cocktail (CSC) and EVs were isolated. iMSC-EVs were characterized by size and EV markers. Biodistribution of intratracheal (IT), intravenous, and intraperitoneal injection of iMSC-EVs in mice was examined using IVIS. Uptake of iMSC-EVs in lung tissue, alveolar macrophages, and RAW264.7 cells was also assessed. C57BL/6 mice were treated with IT/IP iMSC-EVs or vehicle ± IT/IP LPS to induce ALI/acute respiratory distress syndrome and endotoxemia. Lung tissues, plasma, and bronchoalveolar lavage fluid (BALF) were harvested at 24 h. Lung histology, BALF neutrophil/macrophage, cytokine levels, and total protein concentration were measured to assess ALI and inflammation. Survival studies were performed using IP LPS in mice for 3 days. Results: iMSC-EV route of administration resulted in differential tissue distribution. iMSC-EVs were taken up by alveolar macrophages in mouse lung and cultured RAW264.7 cells. IT LPS-treated mice demonstrated marked histologic ALI, increased BALF neutrophils/macrophages and protein, and increased BALF and plasma TNF-α/IL-6 levels. These parameters were attenuated by 2 h before or 2 h after treatment with IT iMSC-EVs in ALI mice. Interestingly, the IT LPS-induced increase in IL-10 was augmented by iMSC-EVs. Mice treated with IP LPS showed increases in TNF-α and IL-6 that were downregulated by iMSC-EVs and LPS-induced mortality was ameliorated by iMSC-EVs. Administration of IT iMSC-EVs 2 h after LPS downregulated the increase in proinflammatory cytokines (TNF-α/IL-6) by LPS and further increased IL-10 levels. Conclusions: iMSC-EVs attenuate the inflammatory effects of LPS on cytokine levels in ALI and IP LPS in mice. LPS-induced mortality was improved with administration of iMSC-EVs.

Influences of elevational gradient on flower size and number of Gentiana lawrencei var. farreri.

Plants can adapt to environmental changes by adjusting their functional traits and biomass allocation. The size and number of flowers are functional traits related to plant reproduction. Life history theory predicts that there is a trade-off between flower size and number, and the trade-off can potentially explain the adaptability of plants. Elevation gradients in mountains provide a unique opportunity to test how plants will respond to climate change. In this study, we tried to better explain the adaptability of the alpine plant Gentiana lawrencei var. farreri in response to climate change. We measured the flower size and number, individual size, and reproductive allocation of G. lawrencei var. farreri during the flowering period along an elevation gradient from 3200 to 4000 m, and explored their relationships using linear mixed-effect models and the structural equation model. We found that with elevation increasing, individual size and flower number decreased and flower size increased, while reproductive allocation remained unchanged. Individual size positively affected flower number, but was not related to flower size; reproductive allocation positively affected flower size, but was not related to flower number; there is a clear trade-off between flower size and number. We also found that elevation decreased flower number indirectly via directly reducing individual size. In sum, this study suggests that G. lawrencei var. farreri can adapt to alpine environments by the synergies or trade-offs among individual size, reproductive allocation, flower size, and flower number. This study increases our understanding of the adaptation mechanisms of alpine plants to climate change in alpine environments.

Dimensional and Doping Engineering of Chiral Perovskites with Enhanced Spin Selectivity for Green Emissive Spin Light-Emitting Diodes.

Chiral perovskites play a pivotal role in spintronics and optoelectronic systems attributed to their chiral-induced spin selectivity (CISS) effect. Specifically, they allow for spin-polarized charge transport in spin light-emitting diodes (LEDs), yielding circularly polarized electroluminescence at room temperature without external magnetic fields. However, chiral lead bromide-based perovskites have yet to achieve high-performance green emissive spin-LEDs, owing to limited CISS effects and charge transport. Herein, we employ dimensional regulation and Sn2+-doping to optimize chiral bromide-based perovskite architecture for green emissive spin-LEDs. The optimized (PEA)x(S/R-PRDA)2-xSn0.1Pb0.9Br4 chiral perovskite film exhibits an enhanced CISS effect, higher hole mobility, and better energy level alignment with the emissive layer. These improvements allow us to fabricate green emissive spin-LEDs with an external quantum efficiency (EQE) of 5.7% and an asymmetry factor |gCP-EL| of 1.1 × 10-3. This work highlights the importance of tailored perovskite architectures and doping strategies in advancing spintronics for optoelectronic applications.

Control of carbon dioxide exchange fluxes by rainfall and biological carbon pump in karst river-lake systems.

As an important component of inland water, the primary factors affecting the carbon cycle in karst river-lake systems require further investigation. In particular, the impacts of climatic factors and the biological carbon pump (BCP) on carbon dioxide (CO2) exchange fluxes in karst rivers and lakes deserve considerable attention. Using quarterly sampling, field monitoring, and meteorological data collection, the spatiotemporal characteristics of CO2 exchange fluxes in Erhai Lake (a typical karst lake in Yunnan, SW China) and its inflow rivers were investigated and the primary influencing factors were analyzed. The average river CO2 exchange flux reached 346.80 mg m-2 h-1, compared to -6.93 mg m-2 h-1 for the lake. The carbon cycle in rivers was strongly influenced by land use within the basin; cultivated and construction land were the main contributors to organic carbon (OC) in the river (r = 0.66, p < 0.01) and the mineralization of OC was a major factor in CO2 oversaturation in most rivers (r = 0.76, p < 0.01). In addition, the BCP effect of aquatic plants and the high pH in karst river-lake systems enhance the ability of water body to absorb CO2, resulting in undersaturated CO2 levels in the lake. Notably, under rainfall regulation, riverine OC and dissolved inorganic carbon (DIC) flux inputs controlled the level of CO2 exchange fluxes in the lake (rOC = 0.78, p < 0.05; rDIC = 0.97, p < 0.01). We speculate that under future climate and human activity scenarios, the DIC and OC input from rivers may alleviate the CO2 limitation of BCP effects in karst eutrophication lakes, possibly enabling aquatic plants to convert more CO2 into OC for burial. The results of this research can help advance our understanding of CO2 emissions and absorption mechanisms in karst river-lake systems.

Neutrophils in glioma microenvironment: from immune function to immunotherapy.

Glioma is a malignant tumor of the central nervous system (CNS). Currently, effective treatment options for gliomas are still lacking. Neutrophils, as an important member of the tumor microenvironment (TME), are widely distributed in circulation. Recently, the discovery of cranial-meningeal channels and intracranial lymphatic vessels has provided new insights into the origins of neutrophils in the CNS. Neutrophils in the brain may originate more from the skull and adjacent vertebral bone marrow. They cross the blood-brain barrier (BBB) under the action of chemokines and enter the brain parenchyma, subsequently migrating to the glioma TME and undergoing phenotypic changes upon contact with tumor cells. Under glycolytic metabolism model, neutrophils show complex and dual functions in different stages of cancer progression, including participation in the malignant progression, immune suppression, and anti-tumor effects of gliomas. Additionally, neutrophils in the TME interact with other immune cells, playing a crucial role in cancer immunotherapy. Targeting neutrophils may be a novel generation of immunotherapy and improve the efficacy of cancer treatments. This article reviews the molecular mechanisms of neutrophils infiltrating the central nervous system from the external environment, detailing the origin, functions, classifications, and targeted therapies of neutrophils in the context of glioma.