GLP-1RA may have varying effects on cardiac structure in patients with ASCVD depending on BMI.

Background: Glucagon-like peptide-1 receptor agonist(GLP-1RA) is commonly used in patients with cardiovascular disease due to its significant improvement in the prognosis of atherosclerotic cardiovascular disease (ASCVD). However, previous studies have primarily focused on obese patients, leaving uncertainty regarding whether GLP-1RA can yield similar cardiovascular benefits in individuals with normal or low body weight. Methods: In this study, we enrolled patients with ASCVD to establish a retrospective cohort. Patients receiving GLP-1RA treatment were assigned to the GLP-1RA group, while a control group was formed by matching age and body mass index (BMI) among patients not receiving GLP-1RA treatment. Each group was further divided into subgroups based on baseline BMI levels: normal weight, overweight, and obesity. A six-month follow-up was conducted to assess changes in patient weight, metabolic indicators, and cardiac structure and function. Results: Among the normal weight subgroup, no significant weight change was observed after six months of GLP-1RA treatment (57.4 ± 4.8 vs. 58.7 ± 9.2, p = 0.063). However, significant weight reduction was observed in the other two subgroups (Overweight group: 70.0 ± 9.1 vs. 73.1 ± 8.2, p = 0.003, Obesity group: 90.5 ± 14.3 vs. 95.5 ± 16.6, p<0.001). Regardless of baseline BMI levels, GLP-1RA demonstrated significant glucose-lowering effects in terms of metabolic indicators. However, GLP-1RA have a more significant effect on improving blood lipids in overweight and obese patients. The effects of GLP-1RA on cardiac structure exhibited variations among patients with different baseline BMI levels. Specifically, it was observed that the improvement in atrial structure was more prominent in patients with normal body weight(LAD: 33.0 (30.3, 35.5) vs. 35.0 (32.5, 37.1), p = 0.018, LAA (18.0 (16.0, 21.5) vs. 18.5 (16.5, 20.5), p = 0.008), while the enhancement in ventricular structure was more significant in obese subjects(LEVDD: 49.8 ± 5.8 vs. 50.2 ± 5.0, p < 0.001, LVMI: 65.1 (56.2, 71.4) vs. 65.8 (58.9, 80.4), p < 0.039). Conclusion: According to the study, it was found that the administration of GLP-1RA can have different effects on cardiac structure in patients with different baseline BMI, In obese patients, improvements in ventricular remodeling may be more associated with weight loss mechanisms, while in patients with normal or low BMI, GLP-1RA may directly improve atrial remodeling through GLP-1 receptors in atrial tissue.

Bacillus sp. alone or combined with salicylic acid inhibited Trichoderma spp. infection on harvested white Hypsizygus marmoreus.

Introduction: White Hypsizygus marmoreus is a popular edible mushroom. It is rich in nutrition and flavor but vulnerable to fungal disease, resulting in nutrient loss and aging. Methods: In this study, the pathogenic fungus Trichoderma spp. BBP-6 and its antagonist Bacillus sp. 1-23 were isolated and identified. The negative effects caused by this pathogen were judged by detecting a series of changes in the infected white H. marmoreus. The effects of Bacillus sp. 1-23 on Trichoderma spp. BBP-6 and the infected white H. marmoreus were detected. The effect of Bacillus sp. 1-23 treatment combined with salicylic acid (SA) was also considered. Results: The results showed that Trichoderma spp. BBP-6 could affect the activities of antioxidant enzymes PAL, POD, CAT, SOD, GR, PPO, and APX to interfere with the stability of the white H. marmoreus antioxidant enzyme system and cause the mushroom severe browning and nutrition loss, as well as general quality deterioration. Bacillus sp. 1-23 could produce chitinase and chitosanase enzymes to inhibit Trichoderma spp. BBP-6 directly. SA reinforced this inhibitory. Bacillus sp. 1-23 alone or combined with SA could help white H. marmoreus from the Trichoderma spp. BBP-6 infection to effectively maintain nutrients, restore and stabilize the antioxidant system, and reduce the production of malondialdehyde, superoxide anion and hydrogen peroxide. Discussion: Thus, such treatments could be considered potential methods to alleviate damage from disease and extend the shelf life of white H. marmoreus.

Salvage haploidentical transplantation for graft failure after first haploidentical allogeneic stem cell transplantation: an updated experience.

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. However, there are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). Herein, we report updated outcomes in 30 patients using this method. The median time of the second transplantation was 96.5 (33-215) days after the first transplantation. Except for one patient who died at +19d and before engraftment, neutrophil engraftments were achieved in all patients at 11 (8-24) days, while platelet engraftments were achieved in 22 (75.8%) patients at 17.5 (9-140) days. The 1-year OS and DFS were 60% and 53.3%, and CIR and TRM was 6.7% and 33.3%, respectively. Compared with the historical group, neutrophil engraftment (100% versus 58.5%, p < 0.001) and platelet engraftment (75.8% versus 32.3%, p < 0.001) were better in the novel regimen group, and OS was also improved (60.0% versus 26.4%, p = 0.011). In conclusion, salvage haploidentical transplantation from a different donor using the novel regimen represents a promising option to rescue patients with graft failure after the first haploidentical transplantation.

Dual-Channel in Spatial-Frequency Domain CycleGAN for perceptual enhancement of transcranial cortical vascular structure and function.

Observing cortical vascular structures and functions using laser speckle contrast imaging (LSCI) at high resolution plays a crucial role in understanding cerebral pathologies. Usually, open-skull window techniques have been applied to reduce scattering of skull and enhance image quality. However, craniotomy surgeries inevitably induce inflammation, which may obstruct observations in certain scenarios. In contrast, image enhancement algorithms provide popular tools for improving the signal-to-noise ratio (SNR) of LSCI. The current methods were less than satisfactory through intact skulls because the transcranial cortical images were of poor quality. Moreover, existing algorithms do not guarantee the accuracy of dynamic blood flow mappings. In this study, we develop an unsupervised deep learning method, named Dual-Channel in Spatial-Frequency Domain CycleGAN (SF-CycleGAN), to enhance the perceptual quality of cortical blood flow imaging by LSCI. SF-CycleGAN enabled convenient, non-invasive, and effective cortical vascular structure observation and accurate dynamic blood flow mappings without craniotomy surgeries to visualize biodynamics in an undisturbed biological environment. Our experimental results showed that SF-CycleGAN achieved a SNR at least 4.13 dB higher than that of other unsupervised methods, imaged the complete vascular morphology, and enabled the functional observation of small cortical vessels. Additionally, the proposed method showed remarkable robustness and could be generalized to various imaging configurations and image modalities, including fluorescence images, without retraining.

DNA Framework-Based Programmable Atom-Like Nanoparticles for Non-Coding RNA Recognition and Differentiation of Cancer Cells.

The cooperative diagnosis of non-coding RNAs (ncRNAs) can accurately reflect the state of cell differentiation and classification, laying the foundation of precision medicine. However, there are still challenges in simultaneous analyses of multiple ncRNAs and the integration of biomarker data for cell typing. In this study, DNA framework-based programmable atom-like nanoparticles (PANs) are designed to develop molecular classifiers for intra-cellular imaging of multiple ncRNAs associated with cell differentiation. The PANs-based molecular classifier facilitates signal amplification through the catalytic hairpin assembly. The interaction between PAN reporters and ncRNAs enables high-fidelity conversion of ncRNAs expression level into binding events, and the assessment of in situ ncRNAs levels via measurement of the fluorescent signal changes of PAN reporters. Compared to non-amplified methods, the detection limits of PANs are reduced by four orders of magnitude. Using human gastric cancer cell lines as a model system, the PANs-based molecular classifier demonstrates its capacity to measure multiple ncRNAs in living cells and assesses the degree of cell differentiation. This approach can serve as a universal strategy for the classification of cancer cells during malignant transformation and tumor progression.

BMP7-Loaded Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Ameliorate Liver Fibrosis by Targeting Activated Hepatic Stellate Cells.

Purpose: Human umbilical cord mesenchymal stem cell (hucMSC)-derived small extracellular vesicles (sEVs) are natural nanocarriers with promising potential in treating liver fibrosis and have widespread applications in the fields of nanomedicine and regenerative medicine. However, the therapeutic efficacy of natural hucMSC-sEVs is currently limited owing to their non-specific distribution in vivo and partial removal by mononuclear macrophages following systemic delivery. Thus, the therapeutic efficacy can be improved through the development of engineered hucMSC-sEVs capable to overcome these limitations. Patients and Methods: To improve the anti-liver fibrosis efficacy of hucMSC-sEVs, we genetically engineered hucMSC-sEVs to overexpress the anti-fibrotic gene bone morphogenic protein 7 (BMP7) in parental cells. This was achieved using lentiviral transfection, following which BMP7-loaded hucMSC-sEVs were isolated through ultracentrifugation. First, the liver fibrosis was induced in C57BL/6J mice by intraperitoneal injection of 50% carbon tetrachloride (CCL4) twice a week for 8 weeks. These mice were subsequently treated with BMP7+sEVs via tail vein injection, and the anti-liver fibrosis effect of BMP7+sEVs was validated using small animal in vivo imaging, immunohistochemistry (IHC), tissue immunofluorescence, and enzyme-linked immunosorbent assay (ELISA). Finally, cell function studies were performed to confirm the in vivo results. Results: Liver imaging and liver histopathology confirmed that the engineered hucMSC-sEVs could reach the liver of mice and aggregate around activated hepatic stellate cells (aHSCs) with a significantly stronger anti-liver fibrosis effect of BMP7-loaded hucMSC-sEVs compared to those of blank or negative control-transfected hucMSC-sEVs. In vitro, BMP7-loaded hucMSC-sEVs promoted the phenotypic reversal of aHSCs and inhibited their proliferation to enhance the anti-fibrotic effects. Conclusion: These engineered BMP7-loaded hucMSC-sEVs offer a novel and promising strategy for the clinical treatment of liver fibrosis.

Electrochemical Benzylic C(sp3)-H Imidation Enabled by Benzoic Acid Derived Radicals.

We developed an electrochemical approach for benzylic C(sp3)-H imidation by virtue of the in situ generated oxygen-centered radicals (OCRs). The electrochemical imidation provides a complementary approach to giving distinct imide products compared with previous acyloxylation products. This protocol exhibits good site selectivity and broad substrate generality. Moreover, the utility of the OCR-mediated protocol was extended to the electrochemical oxidation of silane, and its robustness was also highlighted by the imidation of complex substrates, which would otherwise be inaccessible for previous approaches. A plausible reaction mechanism was proposed to rationalize the experimental observations.

Real-world effectiveness of GLP-1 receptor agonist-based treatment strategies on "time in range" in patients with type 2 diabetes.

Background: Diabetes affects millions of people worldwide annually, and several methods, including medications, are used for its management; glucagon-like peptide-1 receptor agonists (GLP-1RAs) are one such class of medications. The efficacy and safety of GLP-1RAs in treating type 2 diabetes mellitus (T2DM) have been assessed and have been shown to significantly improve time in range (TIR) in several clinical trials. However, presently, there is a lack of real-world evidence on the efficacy of GLP-1RAs in improving TIR. To address this, we investigated the effect of GLP-1RA-based treatment strategies on TIR among patients with T2DM in real-world clinical practice. Methods: This multicenter, retrospective, real-world study included patients with T2DM who had previously used a continuous glucose monitoring (CGM) system and received treatment with GLP-1RAs or oral antidiabetic drugs (OADs). Patients who received OADs served as controls and were matched in a 1:1 ratio to their GLP-1RA counterparts by propensity score matching. The primary endpoint was the TIR after 3-6 months of treatment. Results: According to propensity score matching, 202 patients were equally divided between the GLP-1RA and OAD groups. After 3-6 months of treatment, the TIR values for the GLP-1RA and OAD groups were 76.0% and 65.7%, respectively (p < 0.001). The GLP-1RA group displayed significantly lower time above range (TAR) and mean glucose values than the OAD group (p < 0.001). Subgroup analysis revealed that, compared with the administration of liraglutide, the administration of semaglutide and polyethylene glycol loxenatide (PEG-Loxe) significantly improved TIR over 3-6 months of treatment (p < 0.05). Conclusion: These real-world findings indicate that GLP-1RA-based treatment strategies could be superior to oral treatment strategies for improving TIR among patients with T2DM and that once-weekly GLP-1RA may be more effective than a once-daily GLP-1RA. Clinical trial registration: http://www.chinadrugtrials.org.cn/index.html, identifier number ChiCTR2300073697.

Redox condition changes caused by impacts: Insights from Chang'e-5 lunar glass beads.

Lunar materials are overall more reducing compared with their terrestrial counterparts, but the mechanism remains to be elucidated. In this study, we present a possible explanation for the changes in redox state of the lunar regolith caused by impact events, based on our investigations of the impact glass beads from Chang'e-5 mission. These glass beads contain iron metal grains and show concentration gradients of FeO and K2O (with or without Na2O) from their rims to centers. The compositional profiles exhibit error-function-like shapes, which indicates a diffusion-limited mechanism. Our numerical modeling results suggest that the iron metal grains on the surface of the glass beads were generated through the reduction of FeO by elemental K and (or) Na produced during the impact events. Meanwhile, the iron metal grains inside the bead may have formed due to oxygen diffusion driven by redox potential gradients. Furthermore, our study suggests that impact processes intensify the local reducing conditions, as evidenced by the presence of calcium sulfide particles within troilite grains that coexist with iron metal grains on the surface of the glass beads. This study provides insights into the oxygen diffusion kinetics during the formation of iron metal spherules and sheds light on the changes in redox conditions of lunar materials caused by impact events.

Advances in diagnosis and treatment of non-tuberculous mycobacterial lung disease.

The prevalence of Non-tuberculous Mycobacterial Pulmonary Disease (NTM-PD) is increasing worldwide. The advancement in molecular diagnostic technology has greatly promoted the rapid diagnosis of NTM-PD clinically, and the pathogenic strains can be identified to the species level through molecular typing, which provides a reliable basis for treatment. In addition to the well-known PCR and mNGS methods, there are numerous alternative methods to identify NTM to the species level. The treatment of NTM-PD remains a challenging problem. Although clinical guidelines outline several treatment options for common NTM species infections, in most cases, the therapeutic outcomes of these drugs for NTM-PD often fall short of expectations. At present, the focus of research is to find more effective and more tolerable NTM-PD therapeutic drugs and regimens. In this paper, the latest diagnostic techniques, therapeutic drugs and methods, and prevention of NTM-PD are reviewed.

Enhancing Point-of-Care Diagnosis of African Swine Fever Virus (ASFV) DNA with the CRISPR-Cas12a-Assisted Triplex Amplified Assay.

Accurate, ultrasensitive, and point-of-care (POC) diagnosis of the African swine fever virus (ASFV) remains imperative to prevent its spread and limit the losses incurred. Herein, we propose a CRISPR-Cas12a-assisted triplex amplified colorimetric assay for ASFV DNA detection with ultrahigh sensitivity and specificity. The specific recognition of recombinase aided amplification (RAA)-amplified ASFV DNA could activate the Cas12a/crRNA/ASFV DNA complex, leading to the digestion of the linker DNA (bio-L1) on magnetic beads (MBs), thereby preventing its binding of gold nanoparticles (AuNPs) network. After magnetic separation, the release of AuNPs network comprising a substantial quantity of AuNPs could lead to a discernible alteration in color and significantly amplify the plasmonic signal, which could be read by spectrophotometers or smartphones. By combining the RAA, CRISPR/Cas12a-assisted cleavage, and AuNPs network-mediated colorimetric amplification together, the assay could detect as low as 0.1 copies/µL ASFV DNA within 1 h. The assay showed an accuracy of 100% for the detection of ASFV DNA in 16 swine tissue fluid samples, demonstrating its potential for on-site diagnosis of ASFV.

Exploring the impact of high-altitude de-acclimatization on renal function: The roles of oxidative and endoplasmic reticulum stress in rat models.

BACKGROUND: High-altitude de-acclimatization (HADA) significantly impacts physiological functions when individuals acclimatize to high altitudes return to lower altitudes. This study investigates HADA's effects on renal function and structure in rats, focusing on oxidative and endoplasmic reticulum stress as potential mechanisms of renal injury. OBJECTIVE: To elucidate the pathophysiological mechanisms of renal damage in HADA and evaluate the efficacy of antioxidants Vitamin C (Vit C) and tauroursodeoxycholic acid (TUDCA) in mitigating these effects. METHODS: 88 male Sprague-Dawley rats were randomly divided into a control group, a high-altitude (HA) group, a high-altitude de-acclimatization (HADA) group, and a treatment group. The control group was housed in a sea level environment (500 m), while the HA, HADA, and treatment groups were placed in a simulated high-altitude chamber (5000 m) for 90 days. After this period, the HA group completed the modeling phase; the HADA group was further subdivided into four subgroups, each continuing to be housed in a sea level environment for 3, 7, 14, and 30 days, respectively. The treatment group was split into the Vit C group, the TUDCA group, and two placebo groups, receiving medication for 3 consecutive days, once daily upon return to the sea level. The Vit C group received 100 mg/kg Vit C solution via intravenous injection, the TUDCA group received 250 mg/kg TUDCA solution via intraperitoneal injection, and the placebo groups received an equivalent volume of saline similarly. Serum, urine, and kidney tissues were collected immediately after the modeling phase. Renal function and oxidative stress levels were assessed using biochemical and ELISA methods. Renal histopathology was observed with H&E, Masson's trichrome, PAS, and PASM staining. Transmission electron microscopy was used to examine the ultrastructure of glomeruli and filtration barrier. TUNEL staining assessed cortical apoptosis in the kidneys. Metabolomics was employed for differential metabolite screening and pathway enrichment analysis. RESULTS: Compared to the control and HA groups, the HADA 3-day group (HADA-3D) exhibited elevated renal function indicators, significant pathological damage, observable ultrastructural alterations including endoplasmic reticulum expansion and apoptosis. TUNEL-positive cells significantly increased, indicating heightened oxidative stress levels. Various differential metabolites were enriched in pathways related to oxidative and endoplasmic reticulum stress. Early intervention with Vit C and TUDCA markedly alleviated renal injury in HADA rats, significantly reducing the number of apoptotic cells, mitigating endoplasmic reticulum stress, and substantially lowering oxidative stress levels. CONCLUSION: This study elucidates the pivotal roles of oxidative and endoplasmic reticulum stress in the early-stage renal injury in rats undergoing HADA. Early intervention with the Vit C and TUDCA significantly mitigates renal damage caused by HADA. These findings provide insights into the pathophysiological mechanisms of HADA and suggest potential therapeutic strategies for its future management.

Direct angiographic comparison of different velocity-selective saturation, inversion, and DANTE labeling modules on cerebral arteries.

PURPOSE: This study evaluated the velocity-selective (VS) MRA with different VS labeling modules, including double refocused hyperbolic tangent, eight-segment B1-insensitive rotation, delay alternating with nutation for tailored excitation, Fourier transform-based VS saturation, and Fourier transform-based inversion. METHODS: These five VS labeling modules were evaluated first through Bloch simulations, and then using VSMRA directly on various cerebral arteries of healthy subjects. The relative signal ratios from arterial ROIs and surrounding tissues as well as relative arteria-tissue contrast ratios of different methods were compared. RESULTS: Double refocused hyperbolic tangent and eight-segment B1-insensitive rotation showed very similar labeling effects. Delay alternating with nutation for tailored excitation yielded high arterial signal but with residual tissue signal due to the spatial banding effect. Fourier transform-based VS saturation with half the time of other techniques serves as an efficient nonsubtractive VSMRA method, but the remaining tissue signal still obscured some small distal arteries that were delineated by other subtraction-based VSMRA, allowing more complete cancelation of static tissue. Fourier transform-based inversion produced the highest arterial signal in VSMRA with minimal tissue background. CONCLUSION: This is the first study that angiographically compared five different VS labeling modules. Their labeling characteristics on arteries and tissue and implications for VSMRA and VS arterial spin labeling are discussed.

New insights into the genetic loci related to egg weight and age at first egg traits in broiler breeder.

Egg weight (EW) and age at first egg (AFE) are economically important traits in breeder chicken production. The genetic basis of these traits, however, is far from understood, especially for broiler breeders. In this study, genetic parameter estimation, genome-wide association analysis, meta-analysis, and selective sweep analysis were carried out to identify genetic loci associated with EW and AFE in 6,842 broiler breeders. The study found that the heritability of EW ranged from 0.42 to 0.44, while the heritability of AFE was estimated at 0.33 in the maternal line. Meta-analysis and selective sweep analysis identified two colocalized regions on GGA4 that significantly influenced EW at 32 wk (EW32W) and at 43 wk (EW43W) with both paternal and maternal lines. The genes AR, YIPF6, and STARD8 were located within the significant region (GGA4: 366.86-575.50 kb), potentially affecting EW through the regulation of follicle development, cell proliferation, and lipid transfer etc. The promising genes LCORL and NCAPG were positioned within the significant region (GGA4:75.35-75.42 Mb), potentially influencing EW through pleiotropic effects on growth and development. Additionally, 3 significant regions were associated with AFE on chromosomes GGA7, GGA19, and GGA27. All of these factors affected the AFE by influencing ovarian development. In our study, the genomic information from both paternal and maternal lines was used to identify genetic regions associated with EW and AFE. Two genomic regions and eight genes were identified as the most likely candidates affecting EW and AFE. These findings contribute to a better understanding of the genetic basis of egg production traits in broiler breeders and provide new insights into future technology development.

Kallistatin leads to cognition impairment via downregulating glutamine synthetase.

In many neurodegenerative disorders, such as Alzheimer's disease (AD), glutamate-mediated neuronal excitotoxicity is considered the basis for cognitive impairment. The mRNA and protein expression of SERPINA4(Kallistatin) are higher in patients with AD. However, whether Kallistatin plays a regulatory role in glutamate-glutamine cycle homeostasis remains unclear. In this study, we identified impaired cognitive function in Kallistatin transgenic (KAL-TG) mice. Baseline glutamate levels were elevated and miniature excitatory postsynaptic current (mEPSC) frequency was increased in the hippocampus, suggesting the impairment of glutamate homeostasis in KAL-TG mice. Mechanistically, we demonstrated that Kallistatin promoted lysine acetylation and ubiquitination of glutamine synthetase (GS) and facilitated its degradation via the proteasome pathway, thereby downregulating GS. Fenofibrate improved cognitive memory in KAL-TG mice by downregulating serum Kallistatin. Collectively, our study findings provide insights the mechanism by which Kallistatin regulates cognitive impairment, and suggest the potential of fenofibrate to prevente and treat of AD patients with high levels of Kallistatin.

A three-in-one point-of-care electrochemical sensing platform for accurate monitoring of diabetes.

A three-in-one electrochemical sensing platform was designed for the simultaneous detection of total hemoglobin (tHb), glycated hemoglobin (HbA1c) and HbA1c% by using a dual-aptamer sensing strategy. The developed sensing platform exhibits excellent sensitivity, selectivity, repeatability and long-term stability, and holds promising prospects in the early diagnosis and long-term monitoring of diabetes.

Tau induces inflammasome activation and microgliosis through acetylating NLRP3.

BACKGROUND: Alzheimer's disease (AD) and related Tauopathies are characterised by the pathologically hyperphosphorylated and aggregated microtubule-associated protein Tau, which is accompanied by neuroinflammation mediated by activated microglia. However, the role of Tau pathology in microglia activation or their causal relationship remains largely elusive. METHODS: The levels of nucleotide-binding oligomerisation domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) acetylation and inflammasome activation in multiple cell models with Tau proteins treatment, transgenic mice with Tauopathy, and AD patients were measured by Western blotting and enzyme-linked immunosorbent assay. In addition, the acetyltransferase activity of Tau and NLRP3 acetylation sites were confirmed using the test-tube acetylation assay, co-immunoprecipitation, immunofluorescence (IF) staining, mass spectrometry and molecular docking. The Tau-overexpressing mouse model was established by overexpression of human Tau proteins in mouse hippocampal CA1 neurons through the adeno-associated virus injection. The cognitive functions of Tau-overexpressing mice were assessed in various behavioural tests, and microglia activation was analysed by Iba-1 IF staining and [18F]-DPA-714 positron emission tomography/computed tomography imaging. A peptide that blocks the interaction between Tau and NLRP3 was synthesised to determine the in vitro and in vivo effects of Tau-NLRP3 interaction blockade on NLRP3 acetylation, inflammasome activation, microglia activation and cognitive function. RESULTS: Excessively elevated NLRP3 acetylation and inflammasome activation were observed in 3xTg-AD mice, microtubule-associated protein Tau P301S (PS19) mice and AD patients. It was further confirmed that mimics of 'early' phosphorylated-Tau proteins which increase at the initial stage of diseases with Tauopathy, including TauT181E, TauS199E, TauT217E and TauS262E, significantly promoted Tau-K18 domain acetyltransferase activity-dependent NLRP3 acetylation and inflammasome activation in HEK293T and BV-2 microglial cells. In addition, Tau protein could directly acetylate NLRP3 at the K21, K22 and K24 sites at its PYD domain and thereby induce inflammasome activation in vitro. Overexpression of human Tau proteins in mouse hippocampal CA1 neurons resulted in impaired cognitive function, Tau transmission to microglia and microgliosis with NLRP3 acetylation and inflammasome activation. As a targeted intervention, competitive binding of a designed Tau-NLRP3-binding blocking (TNB) peptide to block the interaction of Tau protein with NLRP3 inhibited the NLRP3 acetylation and downstream inflammasome activation in microglia, thereby alleviating microglia activation and cognitive impairment in mice. CONCLUSIONS: In conclusion, our findings provide evidence for a novel role of Tau in the regulation of microglia activation through acetylating NLRP3, which has potential implications for early intervention and personalised treatment of AD and related Tauopathies.

[Effects of Land Use Structure and Spatial Pattern at Different Temporal and Spatial Scales on Water Quality in Suzhou Creek].

Relationships between land use and water quality of rivers and lakes vary spatially and temporally. These variations were analyzed using spatial analysis and mathematical statistical methods for the Suzhou Creek in Shanghai. Based on the data of water quality and land use in 2001， 2005， 2010， 2015， and 2020， five spatial scales （200， 500， 1 000， 2 000， and 5 000 m reach buffer） of the landscape pattern were extracted using correlation and redundancy analysis to explore the impact of land use composition and spatial pattern on water quality at different spatial and temporal scales. The results showed that： ① the water quality of Suzhou Creek has gradually improved in the past 20 years； other indicators were between Class II to Class IV in 2020 except TN， and TN was the main pollutant. ② The main land use type of the buffer zone was construction land， and the proportion of greenland and woodland showed a small growth trend. ③ The water quality was closely related to landscape pattern， showing temporal and spatial scale effects. On the time scale， indicators such as construction land， agricultural land， landscape dominance， aggregation， and diversity had significant correlations with various water quality parameters， and there was an inverse correlation in 2010 compared with that in other years for NH4+-N， TP， and TN. The landscape pattern in 2001 had the greatest explanation for water quality， with an explanation rate of 93.65%. The impact of greenland and woodland on water quality has begun to emerge in the past 10 years. ④ On the spatial scale， there were significant correlations between greenland and woodland， patch number， landscape shape index， diversity index， and water quality. There was a strong positive regulatory effect of greenland and woodland on NH4+-N， TP， and TN at the scale of 2 000 m. The patch number and landscape shape index had relatively strong regulatory effects on water quality on a larger spatial scale， whereas the Shannon diversity index had a better positive regulatory effect on water quality on a small scale. The landscape pattern within a buffer of 2 000 m had the highest interpretation degree for all factors， with an explanation rate of 68.47%. The study showed that rationally planning the proportion of greenland and woodland within the 2 000 m buffer zone and optimizing its landscape configuration is an important measure to purify the surface water quality of Suzhou Creek.

The Consumption and Diversity Variation Responses of Agricultural Pests and Their Dietary Niche Differentiation in Insectivorous Bats.

Insectivorous bats are generalist predators and can flexibly respond to fluctuations in the distribution and abundance of insect prey. To better understand the effects of bats on arthropod pests, the types of pests eaten by bats and the response of bats to insect prey need to be determined. In this study, we performed DNA metabarcoding to examine prey composition and pest diversity in the diets of four insectivorous species of bats (Hipposideros armiger, Taphozous melanopogon, Aselliscus stoliczkanus, and Miniopterus fuliginosus). We evaluated the correlation between bat activity and insect resources and assessed dietary niche similarity and niche breadth among species and factors that influence prey consumption in bats. We found that the diets of these bats included arthropods from 23 orders and 200 families, dominated by Lepidoptera, Coleoptera, and Diptera. The proportion of agricultural pests in the diet of each of the four species of bats exceeded 40% and comprised 713 agricultural pests, including those that caused severe economic losses. Bats responded to the availability of insects. For example, a higher abundance of insects, especially Lepidoptera, and a higher insect diversity led to an increase in the duration of bat activity. In areas with more abundant insects, the number of bat passes also increased. The dietary composition, diversity, and niches differed among species and were particularly significant between H. armiger and T. melanopogon; the dietary niche width was the greatest in A. stoliczkanus and the narrowest in H. armiger. The diet of bats was correlated with their morphological and echolocation traits. Larger bats preyed more on insects in the order Coleoptera, whereas the proportion of bats consuming insects in the order Lepidoptera increased as the body size decreased. Bats that emitted echolocation calls with a high peak frequency and duration preyed more on insects in the order Mantodea. Our results suggest that dietary niche differentiation promotes the coexistence of different bat species and increases the ability of bats to consume insect prey and agricultural pests. Our findings provide greater insights into the role of bats that prey on agricultural pests and highlight the importance of combining bat conservation with integrated pest management.

A Recombinant Thermophilic and Glucose-Tolerant GH1 ß-Glucosidase Derived from Hehua Hot Spring.

As a crucial enzyme for cellulose degradation, ß-glucosidase finds extensive applications in food, feed, and bioethanol production; however, its potential is often limited by inadequate thermal stability and glucose tolerance. In this study, a functional gene (lq-bg5) for a GH1 family ß-glucosidase was obtained from the metagenomic DNA of a hot spring sediment sample and heterologously expressed in E. coli and the recombinant enzyme was purified and characterized. The optimal temperature and pH of LQ-BG5 were 55 °C and 4.6, respectively. The relative residual activity of LQ-BG5 exceeded 90% at 55 °C for 9 h and 60 °C for 6 h and remained above 100% after incubation at pH 5.0-10.0 for 12 h. More importantly, LQ-BG5 demonstrated exceptional glucose tolerance with more than 40% activity remaining even at high glucose concentrations of 3000 mM. Thus, LQ-BG5 represents a thermophilic ß-glucosidase exhibiting excellent thermal stability and remarkable glucose tolerance, making it highly promising for lignocellulose development and utilization.