Research progress of exosomes from different sources in myocardial ischemia.

Ischemic heart disease refers to the imbalance between the supply and demand of myocardial blood; it has various causes and results in a class of clinical diseases characterized by myocardial ischemia (MI). In recent years, the incidence of cardiovascular disease has become higher and higher, and the number of patients with ischemic heart disease has also increased year by year. Traditional treatment methods include drug therapy and surgical treatment, both of which have limitations. The former maybe develop risks of drug resistance and has more significant side effects, while the latter may damage blood vessels and risk infection. At this stage, a new cell-free treatment method needs to be explored. Many research results have shown that exosomes from different cell sources can protect the ischemic myocardium via intercellular action methods, such as promoting angiogenesis, inhibiting myocardial fibrosis, apoptosis and pyroptosis, and providing a new basis for the treatment of MI. In this review, we briefly introduce the formation and consequences of myocardial ischemia and the biology of exosomes, and then focus on the role and mechanism of exosomes from different sources in MI. We also discuss the role and mechanism of exosomes pretreated with Chinese and Western medicines on myocardial ischemia. We also discuss the potential of exosomes as diagnostic markers and therapeutic drug for MI.

Long-Lasting Chemiluminescence Based on Functionalized Multicolor Protein Capsules for Multiple Visualization Detection of Avian Influenza Virus Biomarkers.

Long-lasting chemiluminescence (CL) emissions are necessary for improving the detection accuracy and expanding the application scope. Here, we have synthesized three oil-in-water (O/W) multicolor protein capsules (LCBA, F/LCBA, and RB/F/LCBA) using a simple ultrasound method and have engineered specific target-triggered catalytic hairpin assembly on their surface and chemiluminescence resonance energy transfer inside. Consequently, three multicolor capsules exhibit excellent structural stability, generate blue-, green-, and red-colored emissions when reacting with H2O2, have long-lasting CL emission over 1 h, and successfully achieve the accurate multiple visualization detection of avian influenza virus subtype targets. Without the need for complex instruments and analysis procedures, the CL imaging assays can be carried out and recorded with a common smartphone. The detection limits for visualizing H1N1, H7N9, and H5N1 are 5.5, 7.6, and 9.0 pM, respectively. There is a linear range between 20.0 and 625 pM and excellent selectivity against interfering DNA. Furthermore, visualization detection has been successfully applied for the detection of H1N1, H7N9, and H5N1 in healthy human serum samples. With these merits, this facile, ultrasensitive, and multiple visualization sensor has potential applications in point-of-care testing and early diagnosis.

Polysaccharides from Flos Sophorae Immaturus ameliorates insulin resistance in IR-HepG2 cells by co-regulating signaling pathways of AMPK and IRS-1/PI3K/AKT.

Four polysaccharides, named FSIP, FSIP-I, FSIP-II and FSIP-III, were isolated from Flos Sophorae Immaturus. Structure characterization revealed that FSIP-I and FSIP-II were types of AG-II-like polysaccharides while FSIP-III featured a RG-II-like structure with high content of GalpA. In vitro experiments showed that FSIPs upregulated HK and PK activities in glycolysis while downregulated G-6-Pase activities in gluconeogenesis. This increased glucose utilization while decreased the glucose synthesis in IR-HepG2 cells, potentially reducing elevated blood sugar levels induced by excess insulin. In terms of antioxidant system, FSIPs decreased the levels of ROS and MDA, and increased the activities of SOD and CAT, enhancing antioxidant capacity to counteract damage caused by insulin resistance in IR-HepG2 cells. To further explore the mechanism, related genes expressions were analyzed. The results found that FSIPs ameliorated insulin resistance via regulating AMPK and IRS-1/PI3K/AKT signal pathways. In the case of AMPK, glucose can be channeled into oxidative (catabolic) pathway, whereas, in the case of IRS-1/PI3K/AKT, glucose can be stored as glycogen (anabolic). This co-modulation could ameliorate insulin resistance by upregulating the glycolysis and repressing the gluconeogenesis in catabolism, and upregulating the glycogen synthesis in anabolism. Additionally, FSIP-III exhibited better anti-insulin resistance activity, attributed to its high content of GalpA.

Activity Variations of CYP2B6 Determine the Metabolic Stratification of Efavirenz.

PURPOSE: To investigate the effects of hepatic enzyme activity variations and CYP2B6 gene polymorphisms on the in vivo and in vitro metabolism of efavirenz. MAIN METHODS: In vitro enzyme systems using rat and human liver microsomes (RLM/HLM) were established, with in vivo studies conducted on Sprague-Dawley rats. Metabolite detection was performed via LC-MS/MS. Human recombinant CYP2B6 microsomes were prepared using a baculovirus-insect cell system and ultracentrifugation, with efavirenz serving as the substrate to study enzyme kinetics. RESULTS: Isavuconazole exhibited an IC50 of 21.14 ± 0.57 µM in RLM, indicating a mixed competitive and noncompetitive mechanism, and an IC50 of 40.44 ± 4.23 µM in HLM, suggesting an anticompetitive mechanism. In rats, coadministration of efavirenz and isavuconazole significantly increased the AUC, Tmax, and Cmax of efavirenz. Co-administration of efavirenz and rifampicin significantly elevated the AUC, Tmax, and Cmax of 8-OH-efavirenz. The activity of CYP2B6.4, 6, and 7 increased significantly compared to CYP2B6.1, with relative clearance ranging from 158.34% to 212.72%. Conversely, the activity of CYP2B6.3, 8, 10, 11, 13-15, 18-21, 23-27, 31-33, and 37 was markedly reduced, ranging from 4.30% to 79.89%. CONCLUSION: Variations in liver enzyme activity and CYP2B6 genetic polymorphisms can significantly alter the metabolism of efavirenz. It provides laboratory-based data for the precise application of efavirenz and other CYP2B6 substrate drugs.

Early pregnancy SARS-COV-2 infection and fetal cardiac and hemodynamic changes.

AIM: Our objective was to investigate the impact on fetal cardiac function and fetal hemodynamics after recovery from severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection in early pregnancy. METHODS: A prospective study involving 60 women in pregnancy who had recovered from a previous SARS-CoV-2 infection and 20 control wemen was performed. Between 11 and 14 weeks of pregnancy, women recovering from infection and controls underwent fetal ultrasound evaluation. Ultrasound parameters assessing cardiac function (TAPSE, MAPSE, E/A ratio) and hemodynamics (DV/S, DV-D, DV-A, DV-TAMV, DV-PI, DV-PLI, DV-PVIV) were measured. RESULTS: Based on ultrasound measurements, the median gestation age of the groups recovering from SARS-CoV-2 infection (RSI) was 12 (0.5) weeks, while the control group's was 12 (0.7) weeks (p = 0.76). The RSI group and the control group didn't indicate statistically significant differences in ultrasound measurements of cardiac function and hemodynamics (p > 0.05). CONCLUSIONS: According to our findings, the infection of SARS-CoV-2 in early pregnancy has no substantial influence on fetal cardiac function and fetal hemodynamics in pregnant women. However, the effect on mid-pregnancy to late-pregnancy is not yet known. Future studies will help elucidate the overall impact on fetal cardiac function of SARS-CoV-2 infection.

Associations between glycated haemoglobin and multi-modal imaging markers of early cardiac aging.

BACKGROUND: Glycated haemoglobin (HbA1c) is a well-established biomarker for diabetes diagnosis and management and is linked to risk of cardiovascular death. However, among adults without cardiovascular disease (CVD) and diabetes, the value of HbA1c in predicting distinct signatures of myocardial ageing has not been explored. METHODS: Subjects, from among older adults without CVD, underwent comprehensive cardiovascular and metabolic assessment. Transthoracic echocardiography measured left ventricular structure and function. Longitudinal left atrial (LA) strain comprising reservoir strain (Ɛs), conduit strain (Ɛe) and booster strain (Ɛa) and their corresponding peak strain rates (SRs, SRe, SRa) were measured using cardiac magnetic resonance (CMR). Blood sampling for biomarkers and cardiovascular examinations were performed. RESULTS: 247 subjects (mean age 71 years, 44.1% female, mean HbA1c 6.0%) were included. HbA1c was significantly associated with E/A ratio (p < 0.0001), conduit strain (Ɛe) (p < 0.0001), conduit strain rate SRe (p < 0.0001), and conduit strain rate to booster strain rate SRe:SRa ratio (p < 0.0001). Multivariate models adjusting for clinical variables such as body mass index, blood pressure, heart rate, diabetes mellitus, smoking, and associated cardiac parameters, demonstrated a persistent independent association. Each unit increase in HbA1c was associated with lower E/A ratio, lower Ɛe, higher SRe and lower SRe:SRa ratio. These associations remained significant after diabetic subjects were excluded. CONCLUSION: Distinct associations were found between HbA1c and myocardial functions of interest in the ageing heart. HbA1c may be useful biomarker for stratifying risks associated with myocardial ageing, independent of diabetes status. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02791139.

Effect of Cr Element in Gas-Shielded Solid Wire for Oil and Gas Long-Distance Pipeline on Microstructure and Low Temperature Toughness of Weld.

In this paper, the influence of Cr element on the mechanical properties of welded joints of gas-shielded solid wire used in oil and gas long-distance pipelines was studied by means of tensile test, impact test, and hardness test, and the microstructure and crack propagation path of weld were characterized by means of an optical microscope, scanning electron microscope, and electron backscattering diffraction. The results show that with the addition of Cr, the strength and toughness of the weld are significantly improved, in which the tensile strength is increased from 607 MPa to 656 MPa, and the impact toughness is increased from 126.37 J to 223.79 J. The proportion of the ferrite side plate in the weld structure is reduced by about 20%, and the effective grain size of acicular ferrite is reduced by about 15%. The reason is that the addition of the Cr element improves the hardenability of the weld structure, inhibits the formation of the ferrite side plate, and promotes the effective refinement of acicular ferrite, which increases the proportion of high-angle grain boundaries in the weld, effectively hindering the crack propagation, improves the crack propagation work, and thus improves the strength and toughness of the weld.

Latent profiles of multi-dimensional sleep characteristics and association with overweight/obesity in Chinese preschool children.

OBJECTIVES: To examine the association between latent profiles of multi-dimensional sleep characteristics and overweight/obesity (OWO) in Chinese preschool children. STUDY DESIGN: The cross-sectional analysis included 3204 preschool children recruited from 24 kindergartens in Shanghai. Parents reported children's demographics and sleep characteristics, including sleep duration, timing and disturbances. Latent profile analysis (LPA) was used to identify sleep subtypes. Logistic regression models were used to evaluate the associations between sleep characteristics/subtypes and OWO. RESULTS: Short sleep duration, late bedtime, long social jetlag and sleep disturbances were significantly associated with increased OWO. However, when considering the interplay of sleep duration and timing, there was no significant association between sleep duration and OWO for children sleeping later than 22:00. Three sleep subtypes were identified based on children's sleep duration, timing and disturbances: "Average Sleepers" (n = 2107, 65.8 %), "Good Sleepers" (n = 481, 15.0 %), and "Poor Sleepers" (n = 616, 19.2 %). "Good Sleepers" had reduced odds of being OWO (AOR, 0.72; 95 % CI, 0.56-0.93) compared to "Average Sleepers", while "Poor Sleepers" showed an increased risk of OWO (AOR, 1.36; 95 % CI, 1.11-1.67). CONCLUSIONS: These findings highlight that improving multiple sleep characteristics simultaneously is a promising option to prevent and intervene childhood obesity.

Bulk and single-cell RNA-seq analyses reveal canonical RNA editing associated with microglial homeostasis and its role in sepsis-associated encephalopathy.

Previous studies have demonstrated the roles of both microglia homeostasis and RNA editing in sepsis-associated encephalopathy (SAE), yet their relationship remains to be elucidated. In this study, we analyzed bulk and single-cell RNA-seq (scRNA) datasets containing 107 brain tissue and microglia samples of mice with microglial depletion and repopulation to explore canonical RNA editing associated with microglia homeostasis and to evaluate its role in SAE. Analysis of brain RNA-Seq of mice revealed hallmarks of microglial repopulation, including peak expressions of Apobec1 and Apobec3 at Day 5 and dramatically changed B2m RNA editing. Significant time-dependent changes in brain RNA editing during microglial depletion and repopulation were primarily observed in synaptic genes, such as Tbc1d24 and Slc1a2. ScRNA-Seq revealed heterogeneous RNA editing among microglia subpopulations and their distinct changes associated with microglia homeostasis. Moreover, repopulated microglia from LPS-induced septic mice exhibited intensified up-regulation of Apobec1 and Apobec3, with distinct RNA editing responses to LPS, mainly involved in immune-related pathways. The hippocampus from septic mice induced by peritoneal contamination and infection showed upregulated Apobec1 and Apobec3 expression, and altered RNA editing in immune-related genes, such as B2m and Mier1, and nervous-related lncRNA Meg3 and Snhg11, both of which were repressed by microglial depletion. Furthermore, the expression of complement-related genes, such as C4b and Cd47, was substantially correlated with RNA editing activity in microglia homeostasis and SAE. Our study demonstrates canonical RNA editing associated with microglia homeostasis and provides new insights into its potential role in SAE.

Rational design of self-amplifying virus-like vesicles with Ebola virus glycoprotein as vaccines.

As emerging and re-emerging pathogens, filoviruses, especially Ebola virus (EBOV), pose a great threat to public health and require sustained attention and ongoing surveillance. More vaccines and antiviral drugs are imperative to be developed and stockpiled to respond to unpredictable outbreaks. Virus-like vesicles, generated by alphavirus replicons expressing homogeneous or heterogeneous glycoproteins (GPs), have demonstrated the capacity of self-propagation and shown great potential in vaccine development. Here, we describe a novel class of EBOV-like vesicles (eVLVs) incorporating both EBOV GP and VP40. The eVLVs exhibited similar antigenicity as EBOV. In murine models, eVLVs were highly attenuated and elicited robust GP-specific antibodies with neutralizing activities. Importantly, a single dose of eVLVs conferred complete protection in a surrogate EBOV lethal mouse model. Furthermore, our VLVs strategy was also successfully applied to Marburg virus (MARV), the representative member of the genus Marburgvirus. Taken together, our findings indicate the feasibility of an alphavirus-derived VLVs strategy in combating infection of filoviruses represented by EBOV and MARV, which provides further evidence of the potential of this platform for universal live-attenuated vaccine development.

New drug combination regimen based on pharmacokinetic characteristics-Erdafitinib combined with sertraline or duloxetine.

The aim of this study is to investigate novel strategies for reducing adverse reactions caused by erdafitinib through a drug combination based on its pharmacokinetic characteristics. The spectrum and characterizations of drugs that can inhibit the metabolism of erdafitinib are examined both in vitro and in vivo. The efficacy of combination regimens are then evaluated using subcutaneous xenograft tumor models. The results demonstrated that sertraline and duloxetine, out of more than 100 screened drugs, inhibited the metabolism of erdafitinib through mixed and non-competitive inhibition, respectively. This inhibition primarily occurred via the CYP2C9 and CYP2D6 pathways. The primary alleles of CYP2C9 and CYP2D6 not only determine the metabolic characteristics of erdafitinib but also influence the strength of drug-drug interactions. Co-administration of sertraline or duloxetine with erdafitinib in rats and mice resulted in nearly a three-fold increase in the blood exposure of erdafitinib and its major metabolite M6. When sertraline or duloxetine was combined with 1/3 of the erdafitinib dosage, the anti-proliferative and pro-apoptotic effects on SNU-16 xenografts were comparable to those of the original full dose of erdafitinib. However, the combination regimen significantly mitigated hyperphosphatemia, retinal damage, intestinal villus damage, and gut microbiome dysbiosis. This study utilized pharmacokinetic methods to propose a new formulation of erdafitinib combined with sertraline or duloxetine. The findings suggest that this combination has potential for clinical co-administration based on a database analysis, thereby providing a novel strategy for anti-tumor treatment with fibroblast growth factor receptor (FGFR) inhibitors.

RNA editing in response to COVID-19 vaccines: unveiling dynamic epigenetic regulation of host immunity.

Background: COVID-19 vaccines are crucial for reducing the threat and burden of the pandemic on global public health, yet the epigenetic, especially RNA editing in response to the vaccines remains unelucidated. Results: Our current study performed an epitranscriptomic analysis of RNA-Seq data of 260 blood samples from 102 healthy and SARS-CoV-2 naïve individuals receiving different doses of the COVID-19 vaccine and revealed dynamic, transcriptome-wide adenosine to inosine (A-to-I) RNA editing changes in response to COVID-19 vaccines (RNA editing in response to COVID-19 vaccines). 5592 differential RNA editing (DRE) sites in 1820 genes were identified, with most of them showing up-regulated RNA editing and correlated with increased expression of edited genes. These deferentially edited genes were primarily involved in immune- and virus-related gene functions and pathways. Differential ADAR expression probably contributed to RNA editing in response to COVID-19 vaccines. One of the most significant DRE in RNA editing in response to COVID-19 vaccines was in apolipoprotein L6 (APOL6) 3' UTR, which positively correlated with its up-regulated expression. In addition, recoded key antiviral and immune-related proteins such as IFI30 and GBP1 recoded by missense editing was observed as an essential component of RNA editing in response to COVID-19 vaccines. Furthermore, both RNA editing in response to COVID-19 vaccines and its functions dynamically depended on the number of vaccine doses. Conclusion: Our results thus underscored the potential impact of blood RNA editing in response to COVID-19 vaccines on the host's molecular immune system.

Flexible and Multifunctional Pressure/Gas Sensors with Polypyrrole-Coated TPU Hierarchical Array.

A promising strategy is proposed for fabricating flexible pressure/gas sensors, which have a microprotuberance and microwrinkle structure at micropillars on their sensing substrates. The sensing substrates were prepared by compression molding thermoplastic polyurethane (TPU; an industrial grade polymer) and subsequent pyrrole polymerization. Benefiting from the hierarchical structure on the sensing substrates, the flexible sensors exhibit high performances in detecting both pressure and ammonia (NH3). Mechanism for the functionalities of the hierarchical structure of the pressure sensors was analyzed. Such unique hierarchical structure endows the interlocked pressure sensor by assembling the substrates prepared at 60 min polymerization time with a relatively high sensitivity in a wider linearity range (1.15 kPa-1, 0-800 Pa), a lower detection limit of 6.2 Pa, and shorter response and recovery times (26/28 ms). The combination of stronger interfacial interaction between the TPU and polypyrrole layer, the mutual support of the interlocked micropillars, and the inherent high resilience of TPU endows the pressure sensor with lower hysteresis, good repeatability and stability, and higher durability (10,000 cycles). The interlocked pressure sensor can detect full-range human physiological activities from weak physiological signals (such as face muscle contraction, heartbeat, and breath) to body movements (such as head, elbow, and foot movement). The gas sensor assembled with the hierarchical sensing substrate prepared at 60 min polymerization time exhibits selective, stable, and faster sensing responses to NH3. The proposed facile and cost-effective preparation strategy can be an excellent candidate for fabricating high-performance and multifunctional sensors.

Spatio-temporal mapping of leaf area index in rice: spectral indices and multi-scale texture comparison derived from different sensors.

Introduction: Monitoring the leaf area index (LAI), which is directly related to the growth status of rice, helps to optimize and meet the crop's fertilizer requirements for achieving high quality, high yield, and environmental sustainability. The remote sensing technology of the unmanned aerial vehicle (UAV) has great potential in precision monitoring applications in agriculture due to its efficient, nondestructive, and rapid characteristics. The spectral information currently widely used is susceptible to the influence of factors such as soil background and canopy structure, leading to low accuracy in estimating the LAI in rice. Methods: In this paper, the RGB and multispectral images of the critical period were acquired through rice field experiments. Based on the remote sensing images above, the spectral indices and texture information of the rice canopy were extracted. Furthermore, the texture information of various images at multiple scales was acquired through resampling, which was utilized to assess the estimation capacity of LAI. Results and discussion: The results showed that the spectral indices (SI) based on RGB and multispectral imagery saturated in the middle and late stages of rice, leading to low accuracy in estimating LAI. Moreover, multiscale texture analysis revealed that the texture of multispectral images derived from the 680 nm band is less affected by resolution, whereas the texture of RGB images is resolution dependent. The fusion of spectral and texture features using random forest and multiple stepwise regression algorithms revealed that the highest accuracy in estimating LAI can be achieved based on SI and texture features (0.48 m) from multispectral imagery. This approach yielded excellent prediction results for both high and low LAI values. With the gradual improvement of satellite image resolution, the results of this study are expected to enable accurate monitoring of rice LAI on a large scale.

Two 2D spin-crossover coordination polymers constructed by [Pd(SCN)4]2- building blocks.

Two new two-dimensional (2D) coordination polymers, [FeII(L)2{PdII(SCN)4}] (L1 = 2-methoxypyrazine, 1; and L2 = (E)-3-(phenyldiazenyl)pyridine, 2), were successfully constructed by using square-planar [Pd(SCN)4]2- building blocks. Complex 1 exhibits complete and one-step spin-crossover (SCO) behavior, while 2 exhibits incomplete and two-step SCO behavior. Further structural insight into this synergy reveals that the flat/flexing [Fe{Pd(SCN)4}]∞ sheets in 1 and 2 are stabilized by interlayered/intralayered supramolecular interactions.

Influence of autonomic nervous dysfunction on eating during hemodialysis sessions: An observational study.

Although some studies have indicated that eating during hemodialysis may induce hypotension and cardiovascular events, some patients still consume food during their treatment. This prospective study was conducted to determine whether the need to eat during hemodialysis treatment was related to abnormal glucose metabolism and autonomic nerve dysfunction. Seventy patients were enrolled in this study, and their demographic features and various laboratory parameters were analyzed. At each routine hemodialysis visit, predialysis, intradialysis, and postdialysis blood pressure measurements were systematically conducted. A 24-hour ambulatory electrocardiogram (ECG) was performed during the hemodialysis interval, and heart rate variability (HRV) values were calculated. Additionally, whether the patients ate during the hemodialysis treatments was recorded. Another 20 people who underwent physical examinations during the same period and were matched for sex and age were included in the control group. The HRV values of the hemodialysis patients were generally lower than those of the control group. Univariate analysis revealed significant differences in sex, age, calcium antagonist use, blood calcium levels, insulin levels, diastolic blood pressure (DBP) measurements, and HRV indices between hemodialysis patients who ate and those who did not eat during hemodialysis (P < .05), whereas there were no significant differences in diabetes status or in the hemoglobin, albumin, blood glucose and C-peptide levels (P > .05). Multivariate analysis revealed that low values for very low frequency (VLF) and postdialysis DBP were risk factors for fasting intolerance during hemodialysis treatments. Autonomic dysfunction may affect whether hemodialysis patients tolerate fasting during dialysis. VLF evaluation may provide information that can be used to develop a more reasonable intradialytic nutritional supplementation method.

The role of RNA modifications in hepatocellular carcinoma: functional mechanism and potential applications.

Hepatocellular carcinoma (HCC) is a highly aggressive cancer with a poor prognosis. The molecular mechanisms underlying its development remain unclear. Recent studies have highlighted the crucial role of RNA modifications in HCC progression, which indicates their potential as therapeutic targets and biomarkers for managing HCC. In this review, we discuss the functional role and molecular mechanisms of RNA modifications in HCC through a review and summary of relevant literature, to explore the potential therapeutic agents and biomarkers for diagnostic and prognostic of HCC. This review indicates that specific RNA modification pathways, such as N6-methyladenosine, 5-methylcytosine, N7-methylguanosine, and N1-methyladenosine, are erroneously regulated and are involved in the proliferation, autophagy, innate immunity, invasion, metastasis, immune cell infiltration, and drug resistance of HCC. These findings provide a new perspective for understanding the molecular mechanisms of HCC, as well as potential targets for the diagnosis and treatment of HCC by targeting specific RNA-modifying enzymes or recognition proteins. More than ten RNA-modifying regulators showed the potential for use for the diagnosis, prognosis and treatment decision utility biomarkers of HCC. Their application value for HCC biomarkers necessitates extensive multi-center sample validation in the future. A growing number of RNA modifier inhibitors are being developed, but the lack of preclinical experiments and clinical studies targeting RNA modification in HCC poses a significant obstacle, and further research is needed to evaluate their application value in HCC treatment. In conclusion, this review provides an in-depth understanding of the complex interplay between RNA modifications and HCC while emphasizing the promising potential of RNA modifications as therapeutic targets and biomarkers for managing HCC.

The kynurenine pathway regulated by intestinal innate lymphoid cells mediates postoperative cognitive dysfunction.

Postoperative cognitive dysfunction (POCD) is a prevalent neurological complication that can impair learning and memory for days, months, or even years after anesthesia/surgery. POCD is strongly associated with an altered composition of the gut microbiota (dysbiosis), but the accompanying metabolic changes and their role in gut-brain communication and POCD pathogenesis remain unclear. Here, the present study reports that anesthesia/surgery in aged mice induces elevated intestinal indoleamine 2,3-dioxygenase (IDO) expression and activity, which shifts intestinal tryptophan (TRP) metabolism toward more IDO-catalyzed kynurenine (KYN) and less gut bacteria-catabolized indoleacetic acid (IAA). Both anesthesia/surgery and intraperitoneal KYN administration induce increased KYN levels that correlate with impaired spatial learning and memory, whereas dietary IAA supplementation attenuates the anesthesia/surgery-induced cognitive impairment. Mechanistically, anesthesia/surgery increases interferon-γ (IFN-γ)-producing group 1 innate lymphoid cells (ILC1) in the small intestine lamina propria and elevates intestinal IDO expression and activity, as indicated by the higher ratio of KYN to TRP. The IDO inhibitor 1-MT and antibodies targeting IFN-γ or ILCs mitigate anesthesia/surgery-induced cognitive dysfunction, suggesting that intestinal ILC1 expansion and the ensuing IFN-γ-induced IDO upregulation may be the primary pathway mediating the shift to the KYN pathway in POCD. The ILC1-KYN pathway in the intestine could be a promising therapeutic target for POCD.

A high-safety lithium-ion battery electrospun separator with Si3N4-assisted sulfonated poly(ether ether ketone) for regulating lithium flux.

The uncontrolled lithium (Li) dendrite growth significantly impacts the safety performance of polymer separators. To mitigate this growth, this study introduces Si3N4 into sulfonated poly(ether Ether Ketone) (SPEEK) and prepares Si3N4/SPEEK composite separators via electrospinning. At the interface between the Si3N4/SPEEK separator and the Li anode, the Si nanowires that form impede Li dendrite growth, thereby enhancing the electrochemical performance of lithium-ion batteries (LIBs). The Li deposition test of the 10 % Si3N4/SPEEK separator can operate for 1000 h without short-circuiting. Additionally, the LiFePO4||Li cell with the 10 % Si3N4/SPEEK separator shows improved initial discharge capacity (157.8 mAh g-1 at 1C) and superior rate performance (125 mAh g-1 at 10C). Moreover, the nano-scale Si3N4 endows the separator with robust thermal and mechanical properties. The FLIR observations reveal that the 10 % Si3N4/SPEEK separator maintains uniform thermal distribution and structural integrity even at 300 °C, ensuring safe battery operation at high temperatures. The additional load of the 10 % Si3N4/SPEEK separator can reach 10.2 mN, which enhances the puncture resistance of the separator. This work provides a solid approach for the application of SPEEK as a high-safety and high-rate LIB separator.