High-Voltage Single-Ion Covalent Organic Framework Electrolytes Enabled by Nitrile Migration Ladders for Lithium Metal Batteries.

The poor electrochemical stability window and low ionic conductivity in solid-state electrolytes hinder the development of safe, high-voltage, and energy-dense lithium metal batteries. Herein, taking advantage of the unique electronic effect of nitrile groups, we designed a novel azanide-based single-ion covalent organic framework (CN-iCOF) structure that possesses effective Li+ transport and high-voltage stability in lithium metal batteries. Density functional theory (DFT) calculations and molecular dynamics (MD) revealed that electron-withdrawing nitrile groups not only resulted in an ultralow HOMO energy orbital but also enhanced Li+ dissociation through charge delocalization, leading to a high tLi+ of 0.93 and remarkable oxidative stability up to 5.6 V (vs. Li+/Li) simultaneously. Moreover, cyanation leveraging Strecker reaction transformed reversible imine-linkage to a stable sp3-carbon-containing azanide anion, which facilitated contorted alignment of transport "ladders" along the one-dimensional anionic channels and the ionic conductivity could reach 1.33 × 10-5 S cm-1 at ambient temperature without any additives. As a result, CN-iCOF allowed operation of solid-state lithium metal batteries with high-voltage cathodes such as LiNi0.8Mn0.1Co0.1O2 (NCM811), demonstrating stable lithium deposition up to 1,100 h and reversible battery cycling at ambient temperature up to 4.5 V, shedding light on the importance of discovering new functionality for forthcoming high-performance batteries.

Screening of postoperative adjuvant chemotherapy-related serum metabolic markers in breast cancer patients based on 1H NMR metabonomics.

Background: Breast cancer (BC) has the highest incidence rate among female malignant tumors. Adjuvant chemotherapy is commonly used to reduce micrometastasis in postoperative patients. However, monitoring the efficacy of chemotherapy in BC is a major challenge in clinical practice. In this study, 1H nuclear magnetic resonance (NMR) metabonomics was performed to explore the serum metabolic characteristics of BC patients before and after adjuvant chemotherapy. Methods: In this study, we collected serum samples from 51 healthy controls and 61 BC patients before and after chemotherapy for 1H NMR metabolomic analysis, and tested the performance of each metabolite and combination segment by the receiver operating characteristic (ROC) curves. Results: Nine metabolites, namely glutamine, citrate, creatine, glycerophosphatidylcholine/phosphatidylcholine, glycine, 1-methylhistidine, lactate, pyruvate and formate had significant changes in BC patients before chemotherapy compared with healthy controls. Lactate, pyruvate, 1-methylhistidine and formate were found to be inversely regulated by chemotherapy. ROC analysis showed that a combination of the four metabolites had good prediction for chemotherapy efficacy with area under the curve of 0.958, sensitivity of 98.36% and specificity of 91.30%. There was no significant correlation between chemotherapy-related metabolites and clinical indicators of cancer patients, indicating that they can be used to evaluate the chemotherapy efficacy of patients with different clinical indicators. Conclusions: Effectively, dynamic and non-invasive metabolic markers for the evaluation of the efficacy of chemotherapy were identified in this study.

Effects of nitrogen application on ammonium assimilation and microenvironment in the rhizosphere of drip-irrigated sunflower under plastic mulch.

This study investigated the effect of nitrogen application on the rhizosphere soil microenvironment of sunflower and clarified the relationship between ammonium assimilation and the microenvironment. In a field experiment high (HN, 190 kg/hm2), medium (MN, 120 kg/hm2) and low nitrogen (CK, 50 kg/hm2) treatments were made to replicate plots of sunflowers using drip irrigation. Metagenomic sequencing was used to analyze the community structure and functional genes involved in the ammonium assimilation pathway in rhizosphere soil. The findings indicated that glnA and gltB played a crucial role in the ammonium assimilation pathway in sunflower rhizosphere soil, with Actinobacteria and Proteobacteria being the primary contributors. Compared with CK treatment, the relative abundance of Actinobacteria increased by 15.57% under MN treatment, while the relative abundance decreased at flowering and maturation stages. Conversely, the relative abundance of Proteobacteria was 28.57 and 61.26% higher in the MN treatment during anthesis and maturation period, respectively, compared with the CK. Furthermore, during the bud stage and anthesis, the abundance of Actinobacteria, Proteobacteria, and their dominant species were influenced mainly by rhizosphere soil EC, ammonium nitrogen (NH4+-N), and nitrate nitrogen (NO3--N), whereas, at maturity, soil pH and NO3--N played a more significant role in shaping the community of ammonium-assimilating microorganisms. The MN treatment increased the root length density, surface area density, and root volume density of sunflower at the bud, flowering, and maturity stages compared to the CK. Moreover, root exudates such as oxalate and malate were positively correlated with the dominant species of Actinobacteria and Proteobacteria during anthesis and the maturation period. Under drip irrigation, applying 120 kg/hm2 of nitrogen to sunflowers effectively promoted the community structure of ammonium-assimilating microorganisms in rhizosphere soil and had a positive influence on the rhizosphere soil microenvironment and sunflower root growth.

[Response of Relationship Between Microplastic Abundance and Nitrogen Metabolism Function Microorganisms and Genes in Water].

The impact of microplastics (MPs) as a new type of pollutant on water pollution has become a research hotspot. To explore the response relationship between the abundance of MPs and nitrogen metabolism function in a freshwater environment, Lake Ulansuhai was used as the research object; the abundance of MPs in the water was detected using a Zeiss microscope, and the distribution characteristics of nitrogen metabolism functional bacteria and functional genes in the water were analyzed using metagenomics sequencing. The correlation analysis method was used to explore the relationship between the abundance of MPs and nitrogen metabolism functional microorganisms and nitrogen metabolism functional genes. The results showed that the presence of MPs in freshwater environments had a higher impact on Cyanobacteria and Firmicutes as the dominant phyla, and the presence of MPs promoted their enrichment and growth. Among the dominant bacterial genera, MPs promoted the growth of Mycobacterium and inhibited Candidatus_Planktopila more significantly, further indicating that in freshwater environments, MPs affected normal nitrogen metabolism by affecting microbial communities, and pathways such as carbon and nitrogen fixation and denitrification were important pathways for MPs to affect nitrogen metabolism. From the perspective of nitrogen metabolism functional genes, it was found that the abundance of MPs significantly affected some functional genes during nitrification (pmoA-amoA, pmoB-amoB, and pmoC-amoC), denitrification (nirK and napA), and dissimilatory nitrate reduction (nrfA) processes (P < 0.05). Moreover, the influence of MPs abundance on different functional genes in the same pathway of nitrogen metabolism varied, making the impact of MPs on aquatic environments very complex; thus, its harm to the water environment cannot be underestimated.

Efficient Air-Processed MA-Free Perovskite Solar Cells by SH-Based Silane Interface Modification.

Air-processed perovskite solar cells (PSCs) with high photoelectric conversion efficiency (PCE) can not only further reduce the production cost but also promote its industrialization. During the preparation of the PSCs in ambient air, the contact of the buried interface not only affects the crystallization of the perovskite film but also affects the interface carrier transport, which is directly related to the performance of the device. Here, we optimize the buried interface by introducing 3-mercaptopropyltrimethoxysilane (MPTMS, (CH3O)3Si(CH2)3SH) on the nickel oxide (NiOx) surface. The crystallization of the perovskite film is improved by enhancing surface hydrophobicity; besides, the SH-based functional group of MPTMS passivates the uncoordinated lead at the interface, which effectively reduces the defects at the bottom interface of perovskite and inhibits the nonradiative recombination at the interface. Moreover, the energy level between the NiOx layer and the perovskite layer is better matched. Based on multiple functions of MPTMS modification, the open circuit voltage of the device is obviously improved, and efficient air-processed methylamine-free (MA-free) PSCs are realized with PCE reaching 21.0%. The device still maintains the initial PCE of 85% after 1000 h aging in the glovebox. This work highlights interface modification in air-processed MA-free PSCs to promote the industrialization of PSCs.

Periapical lesion-derived decellularized extracellular matrix as a potential solution for regenerative endodontics.

Pulp regeneration remains a crucial target in the preservation of natural dentition. Using decellularized extracellular matrix is an appropriate approach to mimic natural microenvironment and facilitate tissue regeneration. In this study, we attempted to obtain decellularized extracellular matrix from periapical lesion (PL-dECM) and evaluate its bioactive effects. The decellularization process yielded translucent and viscous PL-dECM, meeting the standard requirements for decellularization efficiency. Proteomic sequencing revealed that the PL-dECM retained essential extracellular matrix components and numerous bioactive factors. The PL-dECM conditioned medium could enhance the proliferation and migration ability of periapical lesion-derived stem cells (PLDSCs) in a dose-dependent manner. Culturing PLDSCs on PL-dECM slices improved odontogenic/angiogenic ability compared to the type I collagen group. In vivo, the PL-dECM demonstrated a sustained supportive effect on PLDSCs and promoted odontogenic/angiogenic differentiation. Both in vitro and in vivo studies illustrated that PL-dECM served as an effective scaffold for pulp tissue engineering, providing valuable insights into PLDSCs differentiation. These findings pave avenues for the clinical application of dECM's in situ transplantation for regenerative endodontics.

Combined oral low-dose cyclophosphamide endocrine therapy may improve clinical response among patients with metastatic breast cancer via Tregs in TLSs.

Despite limited research on refractory and/or endocrine therapy failure in elderly metastatic breast cancer (MBC) patients, a prior study showed that low-dose oral cyclophosphamide (CY) can improve the overall survival rate of MBC patients, possibly through the immunoregulation of regulatory T cells (Tregs). We preliminarily investigated the combination of endocrine therapy (ET) with oral low-dose CY as salvage therapy in elderly patients via peripheral blood regulatory T-cell analyses. In addition, we evaluated the associations of tumor tertiary lymphoid structures (TLSs) with therapeutic outcomes. HR+/HER2- advanced breast cancer patients who received low-dose CY combined with ET or ET only from April 2015 to August 2021 were enrolled in this retrospective study. The primary outcome was the clinical control rate (CCR), and the secondary outcome was progression-free survival (PFS). Circulating T lymphocyte subpopulations represented by Tregs were monitored during treatment by flow cytometry methods. TLSs wereconfirmed by hematoxylin-eosin staining of pretreatment specimens, and CD3, CD4, and Foxp3 were detected using Opal multicolor immunofluorescence. A total of 85 patients who received CY + ET and 50 patients who received ET only were enrolled, the percentage of patients who received CCR was 73% (62/85) vs. 70% (45/50), and the objective response rate (ORR) was 28% (24/85) vs. 24% (12/50). No deaths occurred during the study period. The mean PFS time was 13 vs. 11 months (P = 0.03). In the CY + ET group, decreases in CD4+/CD25+/Foxp3+ T cells (P < 0.001) were favorable for both clinical control and prolonged PFS (P < 0.001). Compared with patients without TLSs, those with TLSs were more likely to have better clinical control and PFS (mean time = 6 months), and a greater number of Treg cells during TLS pretreatment correlated with longer PFS (P = 0.043). Oral low-dose CY combined with standard ET exerts immunological effects by decreasing Treg levels to achieve improved clinical responses. Moreover, patients with TLSs might benefit more from such therapy than those without TLSs, and a high Treg cell count in TLSs before treatment predicts better therapeutic efficacy.

Deploying a Dipole Electric Field at the CsPbI3 Perovskite/Carbon Interface for Enhancing Hole Extraction and Photovoltaic Performance.

Carbon-based CsPbI3 perovskite solar cells without hole transporter (C-PSCs) have achieved intense attention due to its simple device structure and high chemical stability. However, the severe interface energy loss at the CsPbI3/carbon interface, attributed to the lower hole selectivity for inefficient charge separation, greatly limits device performance. Hence, dipole electric field (DEF) is deployed at the above interface to address the above issue by using a pole molecule, 4-trifluoromethyl-Phenylammonium iodide (CF3-PAI), in which the ─NH3 group anchors on the perovskite surface and the ─CF3 group extends away from it and connects with carbon electrode. The DEF is proven to align with the built-in electric field, that is pointing toward carbon electrode, which well enhances hole selectivity and charge separation at the interface. Besides, CF3-PAI molecules also serve as defect passivator for reducing trap state density, which further suppresses defect-induced non-radiative recombination. Consequently, the CsPbI3 C-PSCs achieve an excellent efficiency of 18.33% with a high VOC of 1.144 V for inorganic C-PSCs without hole transporter.

PLC-CN-NFAT1 signaling-mediated Aß and IL-1ß crosstalk synergistically promotes hippocampal neuronal damage.

Alzheimer's disease (AD) is a progressive neurodegenerative disease. Neuronal calcium overload plays an important role in Aß deposition and neuroinflammation, which are strongly associated with AD. However, the specific mechanisms by which calcium overload contributes to neuroinflammation and AD and the relationship between them have not been elucidated. Phospholipase C (PLC) is involved in regulation of calcium homeostasis, and CN-NFAT1 signaling is dependent on intracellular Ca2+ ([Ca2+]i) to regulate transcription of genes. Therefore, we hypothesized that the PLC-CN-NFAT1 signaling might mediate the interaction between Aß and inflammation to promote neuronal injury in AD. In this experiment, the results showed that the levels of Aß, IL-1ß and [Ca2+]i in the hippocampal primary neurons of APP/PS1 mice (APP neurons) were significantly increased. IL-1ß exposure also significantly increased Aß and [Ca2+]i in HT22 cells, suggesting a close association between Aß and IL-1ß in the development of AD. Furthermore, PLC activation induced significant calcium homeostasis imbalance, cell apoptosis, Aß and ROS production, and significantly increased expressions of CN and NFAT1, while PLC inhibitor significantly reversed these changes in APP neurons and IL-1ß-induced HT22 cells. Further results indicated that PLC activation significantly increased the expressions of NOX2, APP, BACE1, and NCSTN, which were inhibited by PLC inhibitor in APP neurons and IL-1ß-induced HT22 cells. All indications point to a synergistic interaction between Aß and IL-1ß by activating the PLC-CN-NFAT1 signal, ultimately causing a vicious cycle, resulting in neuronal damage in AD. The study may provide a new idea and target for treatment of AD.

Development of a time-resolved immunochromatographic test strip for rapid and quantitative determination of GFAP in serum.

Glial fibrillary acidic protein (GFAP) in serum has been shown as a biomarker of traumatic brain injury (TBI) which is a significant global public health concern. Accurate and rapid detection of serum GFAP is critical for TBI diagnosis. In this study, a time-resolved fluorescence immunochromatographic test strip (TRFIS) was proposed for the quantitative detection of serum GFAP. This TRFIS possessed excellent linearity ranging from 0.05 to 2.5 ng/mL for the detection of serum GFAP and displayed good linearity (Y = 598723X + 797198, R2 = 0.99), with the lowest detection limit of 16 pg/mL. This TRFIS allowed for quantitative detection of serum GFAP within 15 min and showed high specificity. The intra-batch coefficient of variation (CV) and the inter-batch CV were both < 4.0%. Additionally, this TRFIS was applied to detect GFAP in the serum samples from healthy donors and patients with cerebral hemorrhage, and the results of TRFIS could efficiently discern the patients with cerebral hemorrhage from the healthy donors. Our developed TRFIS has the characteristics of high sensitivity, high accuracy, and a wide linear range and is suitable for rapid and quantitative determination of serum GFAP on-site.

Combined blood pressure and heart rate trajectories are associated with prognosis in critically ill patients with acute aortic dissection: A group-based multi-trajectory analysis.

Background: Managing systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) is pivotal in acute aortic dissection (AAD) care. However, no prior studies have jointly analyzed the trajectories of these parameters. This research aimed to characterize their joint longitudinal trajectories and investigate the influence on AAD prognosis. Methods: We included AAD patients from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Using group-based multi-trajectory modeling (GBMTM), we identified combined trajectories of SBP, DBP, and HR within the initial 24 h of intensive care unit (ICU) admission. Cox proportional hazard regression, log-binomial regression, and logistic regression were employed to assess the association between trajectory groups and mortality outcomes. Results: Data from 337 patients were analyzed. GBMTM identified five combined trajectory groups. Group 1 featured rapidly declining SBP and DBP with high pulse pressure and low HR; Group 2 showed high to moderate SBP with slight rebound and persistently low HR; Group 3 displayed persistently moderate BP and HR; Group 4 was characterized by moderate blood pressure with persistently high HR; and Group 5 had high to moderate SBP with slight rebound, high but gradually declining DBP, and slightly high HR. Group 3 demonstrated a lower risk of mortality, with an adjusted hazard ratio of 0.32 (95 % CI, 0.14-0.74), and the adjusted relative risks for in-hospital, 30-day, and 1-year mortalities were 0.37 (95 % CI, 0.15-0.87), 0.25 (95 % CI, 0.10-0.62), and 0.41 (95 % CI, 0.22-0.79), respectively. The time-independent C-index curve demonstrated that the multi-trajectory groups had higher C-index values than any univariate trajectory groups or admission values of SBP, DBP, and HR. Conclusions: Utilization of GBMTM can yield data-driven insights to identify distinct subphenotypes in AAD patients. The combined trajectories of SBP, DBP, and HR within 24 h of ICU admission significantly influenced the mortality rate.

COPII with ALG2 and ESCRTs control lysosome-dependent microautophagy of ER exit sites.

Endoplasmic reticulum exit sites (ERESs) are tubular outgrowths of endoplasmic reticulum that serve as the earliest station for protein sorting and export into the secretory pathway. How these structures respond to different cellular conditions remains unclear. Here, we report that ERESs undergo lysosome-dependent microautophagy when Ca2+ is released by lysosomes in response to nutrient stressors such as mTOR inhibition or amino acid starvation in mammalian cells. Targeting and uptake of ERESs into lysosomes were observed by super-resolution live-cell imaging and focus ion beam scanning electron microscopy (FIB-SEM). The mechanism was ESCRT dependent and required ubiquitinated SEC31, ALG2, and ALIX, with a knockout of ALG2 or function-blocking mutations of ALIX preventing engulfment of ERESs by lysosomes. In vitro, reconstitution of the pathway was possible using lysosomal lipid-mimicking giant unilamellar vesicles and purified recombinant components. Together, these findings demonstrate a pathway of lysosome-dependent ERES microautophagy mediated by COPII, ALG2, and ESCRTS induced by nutrient stress.

Ginsenoside Rg1 alleviates chronic inflammation-induced neuronal ferroptosis and cognitive impairments via regulation of AIM2 - Nrf2 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng is a valuable herb in traditional Chinese medicine. Modern research has shown that it has various benefits, including tonifying vital energy, nourishing and strengthening the body, calming the mind, improving cognitive function, regulating fluids, and returning blood pressure, etc. Rg1 is a primary active component of ginseng. It protects hippocampal neurons, improves synaptic plasticity, enhances cognitive function, and boosts immunity. Furthermore, it exhibits anti-aging and anti-fatigue properties and holds great potential for preventing and managing neurodegenerative diseases (NDDs). AIM OF THE STUDY: The objective of this study was to examine the role of Rg1 in treating chronic inflammatory NDDs and its molecular mechanisms. MATERIALS AND METHODS: In vivo, we investigated the protective effects of Rg1 against chronic neuroinflammation and cognitive deficits in mice induced by 200 µg/kg lipopolysaccharide (LPS) for 21 days using behavioral tests, pathological sections, Western blot, qPCR and immunostaining. In vitro experiments involved the stimulation of HT22 cells with 10 µg/ml of LPS, verification of the therapeutic effect of Rg1, and elucidation of its potential mechanism of action using H2DCFDA staining, BODIPY™ 581/591 C11, JC-1 staining, Western blot, and immunostaining. RESULTS: Firstly, it was found that Rg1 significantly improved chronic LPS-induced behavioral and cognitive dysfunction in mice. Further studies showed that Rg1 significantly attenuated LPS-induced neuronal damage by reducing levels of IL-6, IL-1ß and ROS, and inhibiting AIM2 inflammasome. Furthermore, chronic LPS exposure induced the onset of neuronal ferroptosis by increasing the lipid peroxidation product MDA and regulating the ferroptosis-associated proteins Gpx4, xCT, FSP1, DMT1 and TfR, which were reversed by Rg1 treatment. Additionally, Rg1 was found to activate Nrf2 and its downstream antioxidant enzymes, such as HO1 and NQO1, both in vivo and in vitro. In vitro studies also showed that the Nrf2 inhibitor ML385 could inhibit the anti-inflammatory, antioxidant, and anti-ferroptosis effects of Rg1. CONCLUSIONS: This study demonstrated that Rg1 administration ameliorated chronic LPS-induced cognitive deficits and neuronal ferroptosis in mice by inhibiting neuroinflammation and oxidative stress. The underlying mechanisms may be related to the inhibition of AIM2 inflammasome and activation of Nrf2 signaling. These findings provide valuable insights into the treatment of chronic neuroinflammation and associated NDDs.

[Effect of Polyethylene Microplastics on the Microbial Community of Saline Soils].

Mulching to conserve moisture has become an important agronomic practice in saline soil cultivation, and the effects of the dual stress of salinity and microplastics on soil microbes are receiving increasing attention. In order to investigate the effect of polyethylene microplastics on the microbial community of salinized soils, this study investigated the effects of different types (chloride and sulphate) and concentrations (weak, medium, and strong) of polyethylene (PE) microplastics (1% and 4% of the dry weight mass of the soil sample) on the soil microbial community by simulating microplastic contamination in salinized soil environments indoors. The results showed that:PE microplastics reduced the diversity and abundance of microbial communities in salinized soils and were more strongly affected by sulphate saline soil treatments. The relative abundance of each group of bacteria was more strongly changed in the sulphate saline soil treatment than in the chloride saline soil treatment. At the phylum level, the relative abundance of Proteobacteria was positively correlated with the abundance of fugitive PE microplastics, whereas the relative abundances of Bacteroidota, Actinobacteriota, and Acidobacteria were negatively correlated with the abundance of fugitive PE microplastics. At the family level, the relative abundances of Flavobacteriaceae, Alcanivoracaceae, Halomonadaceae, and Sphingomonasceae increased with increasing abundance of PE microplastics. The KEGG metabolic pathway prediction showed that the relative abundance of microbial metabolism and genetic information functions were reduced by the presence of PE microplastics, and the inhibition of metabolic functions was stronger in sulphate saline soils than in chloride saline soils, whereas the inhibition of genetic information functions was weaker than that in chloride saline soils. The secondary metabolic pathways of amino acid metabolism, carbohydrate metabolism, and energy metabolism were inhibited. It was hypothesized that the reduction in metabolic functions may have been caused by the reduced relative abundance of the above-mentioned secondary metabolic pathways. This study may provide a theoretical basis for the study of the effects of microplastics and salinization on the soil environment under the dual pollution conditions.

Dapagliflozin promotes browning of white adipose tissue through the FGFR1-LKB1-AMPK signaling pathway.

BACKGROUND: Obesity is associated with a wide variety of metabolic disorders that impose significant burdens on patients and society. The "browning" phenomenon in white adipose tissue (WAT) has emerged as a promising therapeutic strategy to combat metabolic disturbances. However, though the anti-diabetic drug dapagliflozin (DAPA) is thought to promote "browning," the specific mechanism of this was previously unclear. METHODS: In this study, C57BL/6 J male mice were used to establish an obesity model by high-fat diet feeding, and 3T3-L1 cells were used to induce mature adipocytes and to explore the role and mechanism of DAPA in "browning" through a combination of in vitro and in vivo experiments. RESULTS: The results show that DAPA promotes WAT "browning" and improves metabolic disorders. Furthermore, we discovered that DAPA activated "browning" through the fibroblast growth factor receptors 1-liver kinase B1-adenosine monophosphate-activated protein kinase signaling pathway. CONCLUSION: These findings provide a rational basis for the use of DAPA in treating obesity by promoting the browning of white adipose tissue.

NMDAR-mediated activation of pannexin1 channels contributes to the detonator properties of hippocampal mossy fiber synapses.

Pannexins are large-pore ion channels expressed throughout the mammalian brain that participate in various neuropathologies; however, their physiological roles remain obscure. Here, we report that pannexin1 channels (Panx1) can be synaptically activated under physiological recording conditions in rodent acute hippocampal slices. Specifically, NMDA receptor (NMDAR)-mediated responses at the mossy fiber to CA3 pyramidal cell synapse were followed by a slow postsynaptic inward current that could activate CA3 pyramidal cells but was absent in Panx1 knockout mice. Immunoelectron microscopy revealed that Panx1 was localized near the postsynaptic density. Further, Panx1-mediated currents were potentiated by metabotropic receptors and bidirectionally modulated by burst-timing-dependent plasticity of NMDAR-mediated transmission. Lastly, Panx1 channels were preferentially recruited when NMDAR activation enters a supralinear regime, resulting in temporally delayed burst-firing. Thus, Panx1 can contribute to synaptic amplification and broadening the temporal associativity window for co-activated pyramidal cells, thereby supporting the auto-associative functions of the CA3 region.

Metabolic-Glycoengineering-Enabled Molecularly Specific Acoustic Tweezing Cytometry for Targeted Mechanical Stimulation of Cell Surface Sialoglycans.

In this study, we developed a novel type of dibenzocyclooctyne (DBCO)-functionalized microbubbles (MBs) and validated their attachment to azide-labelled sialoglycans on human pluripotent stem cells (hPSCs) generated by metabolic glycoengineering (MGE). This enabled the application of mechanical forces to sialoglycans on hPSCs through molecularly specific acoustic tweezing cytometry (mATC), that is, displacing sialoglycan-anchored MBs using ultrasound (US). It was shown that subjected to the acoustic radiation forces of US pulses, sialoglycan-anchored MBs exhibited significantly larger displacements and faster, more complete recovery after each pulse than integrin-anchored MBs, indicating that sialoglycans are more stretchable and elastic than integrins on hPSCs in response to mechanical force. Furthermore, stimulating sialoglycans on hPSCs using mATC reduced stage-specific embryonic antigen-3 (SSEA-3) and GD3 expression but not OCT4 and SOX2 nuclear localization. Conversely, stimulating integrins decreased OCT4 nuclear localization but not SSEA-3 and GD3 expression, suggesting that mechanically stimulating sialoglycans and integrins initiated distinctive mechanoresponses during the early stages of hPSC differentiation. Taken together, these results demonstrated that MGE-enabled mATC uncovered not only different mechanical properties of sialoglycans on hPSCs and integrins but also their different mechanoregulatory impacts on hPSC differentiation, validating MGE-based mATC as a new, powerful tool for investigating the roles of glycans and other cell surface biomolecules in mechanotransduction.

Microbial and environmental medium-driven responses to phosphorus fraction changes in the sediments of different lake types during the freezing period.

The comparative study of the transformation among sediment phosphorus (P) fractions in different lake types is a global issue in lake ecosystems. However, interactions between sediment P fractions, environmental factors, and microorganisms vary with the nutrient status of lakes. In this study, we combine sequential extraction and metagenomics sequencing to assess the characteristics of P fractions and transformation in sediments from different lake types in the Inner Mongolian section of the Yellow River Basin. We then further explore the response of relevant microbial and environmental drivers to P fraction transformation and bioavailability in sediments. The sediments of all three lakes exhibited strong exogenous pollution input characteristics, and higher nutritional conditions led to enhanced sediment P fraction transformation ability. The transformation capacity of the sediment P fractions also differed among the different lake types at the same latitudes, which is affected by many factors such as lake environmental factors and microorganisms. Different drivers reflected the mutual control of weakly adsorbed phosphorus (WA-P), potential active phosphorus (PA-P), Fe/Al-bound phosphorus (NaOH-P), and Ca-bound phosphorus (HCl-P) with the bio-directly available phosphorus (Bio-P). The transformation of NaOH-P in reducing environments can improve P bioavailability, while HCl-P is not easily bioavailable in weakly alkaline environments. There were significant differences in the bacterial community diversity and composition between the different lake types at the same latitude (p < 0.05), and the role of P fractions was stronger in the sediments of lakes with rich biodiversity than in poor biodiversity. Lake eutrophication recovery was somewhat hindered by the microbial interactions of P cycling and P fractions within the sediment. This study provides data and theoretical support for exploring the commonalities and differences among different lake types in the Inner Mongolian section of the Yellow River Basin. Besides, it is representative and typical for promoting the optimization of ecological security patterns in ecologically fragile watersheds.