Multiple sources of water preserved in impact glasses from Chang'e-5 lunar soil.

The existence of molecular H2O and evolution of solar wind-derived water on the lunar surface remain controversial. We report that large amounts of OH and molecular H2O related to solar wind and other multiple sources are preserved in impact glasses from Chang'e-5 (CE5) lunar soil based on reflectance infrared spectroscopy and nanoscale secondary ion mass spectrometry analyses. The estimated water content contributed by impact glasses to CE5 lunar soil was ~72 ppm, including molecular H2O of up to 15 to 25 ppm. Our studies revealed that impact glasses are the main carrier of molecular H2O in lunar soils. Moreover, water in CE5 impact glasses provides a record of complex formation processes and multiple water sources, including water derived from solar wind, deposited by water-bearing meteorites/micrometeorites, and inherited from lunar indigenous water. Our study provides a better understanding of the evolution of surficial water on airless bodies and identifies potential source and storage pathways for water in the terrestrial planets.

Chemical profiling of principle active and toxic constituents in herbs containing aristolochic acids.

Objective: To clear the amounts of the principal active/toxic components in herbs containing aristolochic acids (HCAAs), which are still used as medicine and/or seasoning in many ethnic minority areas of China. Methods: In this study, six major active and toxic components in HCAAs were extracted with ultrasonic extraction. With 6-O-methyl guanosine as internal standard, the target compounds were analyzed qualitatively and quantitatively by using ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) with multiple reaction monitoring-information dependent acquisition-enhanced production ion scanning mode (MRM-IDA-EPI) combined with dynamic background subtraction (DBS) function. Results: The method showed good linearity in the linear range of the six analytes. The limit range of detection was from 0.01 ng/mL to 0.27 ng/mL. All of the detection repeatability, extraction repeatability and accuracy of the method were good. After extraction, the samples remained stable at 15 °C within 24 h. Six analytes were all found in samples except aristolactam (AL) in sample 2, and the contents varied greatly. The contents of these compounds decreased in fruits, leaves and stems of Aristolochia delavayi successively. Conclusion: This method has the advantages of less sample dosage, simple operation, short analysis cycle, high sensitivity, specificity and accuracy. It laid a good foundation for guiding the safety of HCAAs, the in-depth study of pharmacological and toxicological effects and the scientific and standardized processing and compatibility of HCAAs.

A robust vessel-labeling pipeline with high tissue clearing compatibility for 3D mapping of vascular networks.

The combination of vessel-labeling, tissue-clearing, and light-sheet imaging techniques provides a potent tool for accurately mapping vascular networks, enabling the assessment of vascular remodeling in vascular-related disorders. However, most vascular labeling methods face challenges such as inadequate labeling efficiency or poor compatibility with current tissue clearing technology, which significantly undermines the image quality. To address this limitation, we introduce a vessel-labeling pipeline, termed Ultralabel, which relies on a specially designed dye hydrogel containing lysine-fixable dextran and gelatins for double enhancement. Ultralabel demonstrates not only excellent vessel-labeling capability but also strong compatibility with all tissue clearing methods tested, which outperforms other vessel-labeling methods. Consequently, Ultralabel enables fine mapping of vascular networks in diverse organs, as well as multi-color labeling alongside other labeling techniques. Ultralabel should provide a robust and user-friendly method for obtaining 3D vascular networks in different biomedical applications.

Compound Shouwu Jiangzhi Granule regulates triacylglyceride synthesis to alleviate hepatic lipid accumulation.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease with few therapeutic options currently available. Traditional Chinese medicine has been used for thousands of years and exhibited remarkable advantages against such complicated disease for its "multi-component, multi-target and multi-pathway" characteristics. Compound Shouwu Jiangzhi Granule (CSJG) is a clinical empirical prescription for the treatment of NAFLD, but its pharmacological mechanism remains unknown. METHODS: The clinical efficacy of CSJG was retrospectively analyzed in NAFLD patients by comparing blood biomarkers levels and liver MR images before and after CSJG treatment. Then, high-fat/high-fructose (HFHF) diet-induced NAFLD mice were used to further confirm CSJG's effect against hepatic lipid accumulation through hepatic lipid determination and histopathological staining of liver samples. Next, the ingredients of CSJG were determined, and network pharmacology analysis was performed to predict potential targets of CSJG, followed by quantitative PCR (qPCR) and western blotting for verification. Then, lipidomics study was carried out to further explore the anti-NAFLD mechanism of CSJG from the perspective of triacylglyceride (TAG) synthesis but not free fatty acid (FFA) synthesis. The enzymes involved in this process were assayed by qPCR and western blotting. The potential interactions between the key enzymes of TAG synthesis and the active ingredients of CSJG were analyzed by molecular docking. RESULTS: CSJG attenuated blood lipid levels and hepatic fat accumulation in both NAFLD patients and mice. Although network pharmacology analysis revealed the FFA synthesis pathway, CSJG only slightly affected it. Through lipidomics analysis, GSJG was found to significantly block the synthesis of diglycerides (DAGs) and TAGs in the liver, with decreased DGAT2 and increased PLD1 protein expression, which diverted DAGs from the synthesis of TAGs to the production of PEs, PCs and PAs and thus lowed TAGs level. Molecular docking suggested that rhein, luteolin and liquiritigenin from CSJG might be involved in this regulation. CONCLUSION: Clinical and experimental evidence demonstrated that CSJG is a promising agent for the treatment of NAFLD. CSJG regulated TAGs synthesis to alleviate hepatic lipid accumulation. Rhein, luteolin and liquiritigenin from CSJG might play a role in it.

12-O-deacetyl-phomoxanthone A inhibits ovarian tumor growth and metastasis by downregulating PDK4.

AIMS: The xanthone dimer 12-O-deacetyl-phomoxanthone A (12-ODPXA) was extracted from the secondary metabolites of the endophytic fungus Diaporthe goulteri. The 12-ODPXA compound exhibited anticancer properties in murine lymphoma; however, the anti-ovarian cancer (OC) mechanism has not yet been explored. Therefore, the present study evaluated whether 12-ODPXA reduces OC cell proliferation, metastasis, and invasion by downregulating pyruvate dehydrogenase kinase (PDK)4 expression. METHODS: Cell counting kit-8, colony formation, flow cytometry, wound healing, and transwell assays were performed to examine the effects of 12-ODPXA on OC cell proliferation, apoptosis, migration, and invasion. Transcriptome analysis was used to predict the changes in gene expression. Protein expression was determined using western blotting. Glucose, lactate, and adenosine triphosphate (ATP) test kits were used to measure glucose consumption and lactate and ATP production, respectively. Zebrafish xenograft models were constructed to elucidate the anti-OC effects of 12-ODPXA. RESULTS: The 12-ODPXA compound inhibited OC cell proliferation, migration, invasion, and glycolysis while inducing cell apoptosis via downregulation of PDK4. In vivo experiments showed that 12-ODPXA suppressed tumor growth and migration in zebrafish. CONCLUSION: Our data demonstrate that 12-ODPXA inhibits ovarian tumor growth and metastasis by downregulating PDK4, revealing the underlying mechanisms of action of 12-ODPXA in OC.

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.

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.

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.

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.

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.

Socioeconomic status, personality, and major mental disorders: a bidirectional Mendelian randomization study.

Previous research has suggested a correlation between socioeconomic status (SES) and mental diseases, while personality traits may be associated with SES and the risk of mental disorders. However, the causal nature of these associations remains largely uncertain. Our Mendelian randomization (MR) study aims to explore the bidirectional causality between SES and mental disorders, as well as to evaluate the potential mediating role of personality in these associations. Using bidirectional MR approach, we assessed the causality between SES indicators and mental disorders. We then used a two-step MR method to further investigate whether and to what extent personality mediates the causal associations in Caucasians. The forward MR analyses identified that years of education, household income, age at first birth and the Townsend deprivation index had a causal association with at least one mental disorder. The reverse MR analyses identified causal effects of genetically predicted schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder on five SES indicators. Importantly, mediation analysis showed that neuroticism partly mediated the causality of household income and years of education on major depressive disorder, respectively. In brief, our study confirmed the bidirectional relationship between SES and mental disorders. We also revealed the role of neuroticism in mediating the association between SES and major depressive disorder, highlighting the importance of considering both socioeconomic and personality factors in mental health research and interventions.

Transcription Factor McHB7 Improves Ice Plant Drought Tolerance through ABA Signaling Pathway.

As global climate change continues, drought episodes have become increasingly frequent. Studying plant stress tolerance is urgently needed to ensure food security. The common ice plant is one of the model halophyte plants for plant stress biology research. This study aimed to investigate the functions of a newly discovered transcription factor, Homeobox 7 (HB7), from the ice plant in response to drought stress. An efficient Agrobacterium-mediated transformation method was established in the ice plant, where ectopic McHB7 expression may be sustained for four weeks. The McHB7 overexpression (OE) plants displayed drought tolerance, and the activities of redox enzymes and chlorophyll content in the OE plants were higher than the wild type. Quantitative proteomics revealed 1910 and 495 proteins significantly changed in the OE leaves compared to the wild type under the control and drought conditions, respectively. Most increased proteins were involved in the tricarboxylic acid cycle, photosynthesis, glycolysis, pyruvate metabolism, and oxidative phosphorylation pathways. Some were found to participate in abscisic acid signaling or response. Furthermore, the abscisic acid levels increased in the OE compared with the wild type. McHB7 was revealed to bind to the promoter motifs of Early Responsive to Dehydration genes and abscisic acid-responsive genes, and protein-protein interaction analysis revealed candidate proteins responsive to stresses and hormones (e.g., abscisic acid). To conclude, McHB7 may contribute to enhance plant drought tolerance through abscisic acid signaling.

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.

In Situ Engineering Cancer Mask to Immobilize Tumor Cells and Block Metastasis.

This work reports a new concept of cancer mask in situ to alter the specific biological functions of cancer cells. Metastatic cancer cells are highly invasive in part due to the presence of the glycan matrix in the cell membrane. Using a rational designed bio-orthogonal reaction, the cancer cell surface is reconstructed in situ by incorporating endogenous polysialic acids in the glycan matrix on the cell membrane to form a mesh-like network, called cancer mask. The network of the glycan matrix can not only immobilize cancer cells but also effectively block the stimulation of metastasis promoters to tumor cells and inhibit the formation of epithelial to mesenchymal transition (EMT), causing metastatic cancer cells incarceration. The results demonstrate a new strategy to control and even eliminate the cancer metastasis that is a major cause of treatment failure and poor patient outcome.

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.

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.

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.

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.

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.

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.