Qian Yang Yu Yin Granule prevents hypertensive cardiac remodeling by inhibiting NLRP3 inflammasome activation via Nrf2.

ETHNOPHARMACOLOGICAL RELEVANCE: Qian Yang Yu Yin Granule (QYYYG), a traditional Chinese poly-herbal formulation, has been validated in clinical trials to mitigate cardiac remodeling (CR), and cardiac damage in patients with hypertension. However, the specific mechanism remains unclear. AIM OF THE STUDY: This study explored the potential effects and potential mechanisms of QYYYG on hypertensive CR by combining various experimental approaches. MATERIALS AND METHODS: Spontaneously hypertensive rats (SHRs) were used as a model of hypertensive CR, followed by QYYYG interventions. Blood pressure, cardiac function and structure, histopathological changes, and myocardial inflammation and oxidative stress were tested to assess the efficacy of QYYYG in SHRs. For in vitro experiments, a cell model of myocardial hypertrophy and injury was constructed with isoprenaline. Cardiomyocyte hypertrophy, oxidative stress, and death were examined after treatment with different concentrations of QYYYG, and transcriptomics analyses were performed to explore the underlying mechanism. Nrf2 and the ROS/NF-κB/NLRP3 inflammasome pathway were detected. Thereafter, ML385 and siRNAs were used to inhibit Nrf2 in cardiomyocytes, so as to verify whether QYYYG negatively regulates the NLRP3 inflammasome by targeting Nrf2, thereby ameliorating the associated phenotypes. Finally, high performance liquid chromatography (HPLC) was conducted to analyze the active ingredients in QYYYG, and molecular docking was utilized to preliminarily screen the compounds with modulatory effects on Nrf2 activities. RESULTS: QYYYG improved blood pressure, cardiac function, and structural remodeling and attenuated myocardial inflammation, oxidative stress, and cell death in SHRs. The transcriptomics results showed that the inflammatory response might be crucial in pathological CR and that Nrf2, which potentially negatively regulates the process, was upregulated by QYYYG treatment. Furthermore, QYYYG indeed facilitated Nrf2 activation and negatively regulated the ROS/NF-κB/NLRP3 inflammasome pathway, therefore ameliorating the associated phenotypes. In vitro inhibition or knockdown of Nrf2 weakened or even reversed the repressive effect of QYYYG on ISO-induced inflammation, oxidative stress, pyroptosis, and the NLRP3 inflammasome activation. Based on the results of HPLC and molecular docking, 30 compounds, including cafestol, genistein, hesperetin, and formononetin, have binding sites to Keap1-Nrf2 protein and might affect the activity or stability of Nrf2. CONCLUSION: In conclusion, the alleviatory effect of QYYYG on hypertensive CR is related to its regulation of Nrf2 activation. Specifically, QYYYG blocks the activation of the NLRP3 inflammasome by boosting Nrf2 signaling and depressing myocardial inflammation, oxidative stress, and pyroptosis, thereby effectively ameliorating hypertensive CR.

Effect of different nitrogen source and Saccharomyces cerevisiae strain on volatile sulfur compounds and their sensory effects in chardonnay wine.

Three commercial Saccharomyces cerevisiae strains with low, medium, and high H2S-producing capacity were chosen to investigate the effect of yeast assimilable nitrogen (YAN) levels and composition on volatile compounds in a chemically defined medium, specifically high, medium, and low initial YAN levels with varying proportions of DAP or sulfur-containing amino acids (cysteine and methionine). The results revealed that the initial YAN containing a larger proportion of diammonium phosphate resulted in a higher YAN consumption rate during the early stages of fermentation. The yeast strain had a greater effect on the volatiles than the YAN level and composition. Keeping the total YAN constant, a higher proportion of sulfur-containing amino acids resulted in a considerably higher production of 3-methylthiopropanol. The sensory impact of three key volatile sulfur compounds was investigated in a Chardonnay wine matrix, indicating that 3-methylthiopropanol at subthreshold or greater concentrations was effective in enhancing the cantaloupe aroma.

3D printing of thermochromic multilayer flexible film for multilevel information encryption.

Flexible thermal-responsive encryption devices are widely employed in information encryption and anti-counterfeiting due to their cost-effectiveness and dynamic data encryption and decryption capabilities. However, most current devices are limited to a single layer of encryption, resulting in restricted decryption methods and storage capacity, as well as reliance on external heating. In this study, we integrate multiple layers of encryption within a single device and introduce self-heating thermochromic technology along with infrared thermal imaging encryption to establish a novel concept of a multilayer flexible encryption system. By combining infrared encryption and thermochromic encryption in three-dimensional space enhances the difficulty level for decryption while achieving high storage capacity for information. The internally integrated conductive heating layer within the multilayer structure facilitates rapid and adjustable heating for thermochromic patterns, eliminating the need for external heat sources. Furthermore, we employ a low-cost customizable multi-material integrated 3D printing process for manufacturing multilayer flexible encryption devices. This research presents an innovative solution for designing and fabricating high-density multilevel flexible encryption devices.

Accessing bands with extended quantum metric in kagome Cs2Ni3S4 through soft chemical processing.

Flat bands that do not merely arise from weak interactions can produce exotic physical properties, such as superconductivity or correlated many-body effects. The quantum metric can differentiate whether flat bands will result in correlated physics or are merely dangling bonds. A potential avenue for achieving correlated flat bands involves leveraging geometrical constraints within specific lattice structures, such as the kagome lattice; however, materials are often more complex. In these cases, quantum geometry becomes a powerful indicator of the nature of bands with small dispersions. We present a simple, soft-chemical processing route to access a flat band with an extended quantum metric below the Fermi level. By oxidizing Ni-kagome material Cs2Ni3S4 to CsNi3S4, we see a two orders of magnitude drop in the room temperature resistance. However, CsNi3S4 is still insulating, with no evidence of a phase transition. Using experimental data, density functional theory calculations, and symmetry analysis, our results suggest the emergence of a correlated insulating state of unknown origin.

Discussion on clinical application and regularity of the theory of "mind-regulating" in clinical acupuncture and moxibustion treatment. / "调神"思想在针灸临床中的运用概况及规律探讨.

The active role of "Shen" (mind) in the process of disease treatment has always been valued by scholars of traditional Chinese medicine (TCM). "Tiaoshen" (mind-regulating) is regarded as the fundamental component of TCM therapy. "Mind-regulating" acupuncture and moxibustion therapy, as a treatment method for both body and mind, is consistent with the present bio-psycho-social medical model. In recent years, a large number of clinical studies have confirmed the exact efficacy of "mind-regulating" acupuncture and moxibustion therapy. This article reviewed the clinical applications of that in psychosomatic diseases, neurological diseases, and digestive diseases over the last decade. This article also summarized the research progress of various "mind-regulating" acupuncture and moxibustion methods, investigated the theoretical connotations of "Tongdu Tiaoshen" (dredging Governor Vessel and regulating mind) acupuncture, "Shugan Tiaoshen" (soothing liver and regulating mind) acupuncture, and the "Tiaoshen needling technique" (mind-regulating needling technique), and generalized the main acupoint selection rules. Lastly, future development directions were provided for the theoretical basis of clinical application of "mind-regulating" acupuncture and moxibustion therapy for further improvement.

A predictive model for L-T4 dose in postoperative DTC after RAI therapy and its clinical validation in two institutions.

Purpose: To develop a predictive model using machine learning for levothyroxine (L-T4) dose selection in patients with differentiated thyroid cancer (DTC) after resection and radioactive iodine (RAI) therapy and to prospectively validate the accuracy of the model in two institutions. Methods: A total of 266 DTC patients who received RAI therapy after thyroidectomy and achieved target thyroid stimulating hormone (TSH) level were included in this retrospective study. Sixteen clinical and biochemical characteristics that could potentially influence the L-T4 dose were collected; Significant features correlated with L-T4 dose were selected using machine learning random forest method, and a total of eight regression models were established to assess their performance in prediction of L-T4 dose after RAI therapy; The optimal model was validated through a two-center prospective study (n=263). Results: Six significant clinical and biochemical features were selected, including body surface area (BSA), weight, hemoglobin (HB), height, body mass index (BMI), and age. Cross-validation showed that the support vector regression (SVR) model was with the highest accuracy (53.4%) for prediction of L-T4 dose among the established eight models. In the two-center prospective validation study, a total of 263 patients were included. The TSH targeting rate based on constructed SVR model were dramatically higher than that based on empirical administration (Rate 1 (first rate): 52.09% (137/263) vs 10.53% (28/266); Rate 2 (cumulative rate): 85.55% (225/263) vs 53.38% (142/266)). Furthermore, the model significantly shortens the time (days) to achieve target TSH level (62.61 ± 58.78 vs 115.50 ± 71.40). Conclusions: The constructed SVR model can effectively predict the L-T4 dose for postoperative DTC after RAI therapy, thus shortening the time to achieve TSH target level and improving the quality of life for DTC patients.

Genome-wide characterization of dynamic DNA 5-hydroxymethylcytosine and TET2-related DNA demethylation during breast tumorigenesis.

BACKGROUND: Breast tumorigenesis is a complex and multistep process accompanied by both genetic and epigenetic dysregulation. In contrast to the extensive studies on DNA epigenetic modifications 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) in malignant breast tumors, their roles in the early phases of breast tumorigenesis remain ambiguous. RESULTS: DNA 5hmC and 5mC exhibited a consistent and significant decrease from usual ductal hyperplasia to atypical ductal hyperplasia and subsequently to ductal carcinoma in situ (DCIS). However, 5hmC showed a modest increase in invasive ductal breast cancer compared to DCIS. Genomic analyses showed that the changes in 5hmC and 5mC levels occurred around the transcription start sites (TSSs), and the modification levels were strongly correlated with gene expression levels. Meanwhile, it was found that differentially hydroxymethylated regions (DhMRs) and differentially methylated regions (DMRs) were overlapped in the early phases and accompanied by the enrichment of active histone marks. In addition, TET2-related DNA demethylation was found to be involved in breast tumorigenesis, and four transcription factor binding sites (TFs: ESR1, FOXA1, GATA3, FOS) were enriched in TET2-related DhMRs/DMRs. Intriguingly, we also identified a certain number of common DhMRs between tumor samples and cell-free DNA (cfDNA). CONCLUSIONS: Our study reveals that dynamic changes in DNA 5hmC and 5mC play a vital role in propelling breast tumorigenesis. Both TFs and active histone marks are involved in TET2-related DNA demethylation. Concurrent changes in 5hmC signals in primary breast tumors and cfDNA may play a promising role in breast cancer screening.

Complications during and after ICU stay are associated with increased mortality after status epilepticus.

BACKGROUND: Status Epilepticus (SE) is a neurological emergency with high mortality rate that often requires admission in Intensive Care Units (ICU). Several factors of worse outcome have been identified in prior studies. The aim of our study was to determine the mortality in ICU and in the ward in patients with SE admitted to an ICU and to identify risk factors of mortality. METHODS: Retrospective cohort study of patients admitted with SE treated in the ICU of a tertiary medical center between 2015 and 2020. The primary outcome measure was mortality in the ICU (ICU death) or in the ward after ICU discharge (post-ICU death). RESULTS: 252 patients were included, with a mean age of 63 (±16) years and 127 males (50 %). 58 died in the ICU, 27 died in the ward. Overall mortality was associated with a higher burden of comorbidities (OR:1.28, p < 0.001), the use of vasopressors (OR: 5.65, p < 0.001) and a higher burden of ICU complications (OR: 1.32, p = 0.002). Mortality rate was higher in more severe SE episodes (nonconvulsive, acute symptomatic and refractoriness. In-ICU mortality was associated with the use of vasopressors (OR: 7.92, p<0.001) and mechanical ventilation (OR: 3.13, p = 0.031), the length of in-ICU stay (OR: 0.91, p = 0.005) and a higher burden of ICU complications (OR: 1.37, p = 0.001). Compared to post-ICU deaths, ICU deaths also had higher Sequential Organ Failure Assessment (SOFA) score on ICU admission (p<0.001). Post-ICU mortality was associated with a higher burden of comorbidities (OR: 1.34, p<0.001), a higher burden of complications after ICU-discharge (OR: 1.33, p = 0.01), and more often refractory SE episode (OR: 2.63, p = 0.01). Compared to survivors, post-ICU deaths experienced mostly infectious and respiratory complications, after ICU-discharge. CONCLUSION: Death was more frequent in more severe SE episodes: non convulsive semiology, acute etiology, and refractoriness. In-ICU, post-ICU and all-cause mortality in patients with SE admitted to an ICU are all associated with a higher burden of comorbidities, which are non-modifiable prognostic factors, but also with a higher burden of complications, some of which are preventable, such as respiratory infections.

Generation of oxygen vacancies in CuO/TiO2 heterojunction induced by diatomite for highly efficient UV-Vis-IR driven photothermal catalytic oxidation of HCHO.

Photothermal catalytic oxidation is a promising and sustainable method for the degradation of indoor formaldehyde (HCHO). However, the excessively high surface temperature of existing photothermal catalysts during catalysis hinders the effective adsorption and degradation of formaldehyde under static conditions. Catalyst loading and oxygen vacancies (OVs) modulation are commonly employed strategies to reduce the photothermal catalytic temperature and enhance the efficiency of photothermal catalytic oxidation. In this work, a p-n type CuO/TiO2 heterojunction is successfully loaded onto diatomite using a wet precipitation method. Under the irradiation of a 300W xenon lamp, the prepared composite material achieved a 100% removal rate of HCHO within 2 h, with a 98% conversion rate to CO2, surpassing the performance of both individual photocatalysts and thermocatalysts. Additionally, by adjusting conditions such as light irradiation and temperature, we have demonstrated that this material exhibits synergistic photothermal catalytic properties. Based on HRTEM, XPS, Raman, and EPR analyses, the introduction of diatomite as a catalyst support was shown to effectively increase the number of OVs. Experimental results, along with O2-TPD, photoelectrochemical characterization, and radical detection, demonstrate that the presence of OVs enhances the oxidative efficiency of both photocatalysis and thermocatalysis, as well as the UV-Vis-IR photothermal catalytic performance. The ternary composite material generates weak hydroxyl (•OH) and superoxide (•O2-) radical under high-temperature with dark conditions, indicating its catalytic oxidation activity under this condition. The increase in temperature and the expansion of the spectral range both enhance the generation of these radicals. In summary, this work demonstrates that the use of diatomite as a support increases the material's specific surface area and OVs content, thereby enhancing adsorption and photothermal catalysis. It elucidates the enhanced catalytic degradation mechanism of this mineral-based photothermal catalyst.

Meta-Analysis of MRI in Predicting Early Response to Radiotherapy and Chemotherapy in Esophageal Cancer.

RATIONALE AND OBJECTIVES: At present, the application of magnetic resonance imaging (MRI) in the prediction of response to neoadjuvant therapy and concurrent chemoradiotherapy for the treatment of esophageal cancer still needs to be further explored, and its early differential value remains controversial, thus we carried out this systematic review with a meta-analysis. In the application, different MRI sequences and corresponding parameters are used for the differential diagnosis of the response to neoadjuvant therapy and concurrent chemoradiotherapy. METHODS: All relevant studies evaluated the efficacy and response to MRI in neoadjuvant therapy or concurrent chemoradiotherapy for esophageal cancer on Pubmed, Embase, Cohrane Library, and Web of Science databases published before October 10, 2023 (inclusive) were systematically searched. A revised tool was used to assess the quality of diagnostic accuracy studies (QUADAS-2) to assess the risk of bias in the included original studies. A subgroup analysis of MRI sequences diffusion weighted imaging (DWI), dynamic contrast enhanced (DCE) and their corresponding different parameters, as well as the acquisition timepoints (before and after treatment) for different parameters, was performed during the meta-analysis. The bivariate mixed-effects model was used for meta-analysis. RESULTS: 21 studies were finally included, involving 1128 patients with esophageal cancer. The sensitivity, specificity, and area under receiver operating characteristic curve (ROC curve) of DWI sequence for identifying response to concurrent chemoradiotherapy were 0.82 (95% CI: 0.74-0.87), 0.81 (95% CI: 0.72-0.87) and 0.88 (95% CI: 0.56-0.98), respectively. The sensitivity, specificity, and area under ROC curve of DCE sequence for identifying response to concurrent chemoradiotherapy were 0.78 (95% CI: 0.70-0.84), 0.65 (95% CI: 0.59-0.70) and 0.73 (95% CI: 0.50-0.88), respectively. In patients with esophageal cancer, the sensitivity, specificity, and area under the ROC curve of DWI sequences for identifying response to neoadjuvant therapy were 0.80 (95% CI: 0.69 - 0.88), 0.81 (95% CI: 0.69 - 0.89), and 0.88 (95% CI: 0.34 - 0.99), respectively; the sensitivity, specificity, and area under the ROC curve of DCE sequences for identifying response to neoadjuvant therapy were 0.84 (95% CI: 0.76 - 0.90), 0.61 (95% CI: 0.53 - 0.68), and 0.70 (95% CI: 0.27 - 0.94), respectively. CONCLUSIONS: Based on the available evidence, MRI had a very good value in the early identification of response to neoadjuvant therapy and concurrent chemoradiotherapy for esophageal cancer, especially DWI. Apparent diffusion coefficient (ADC) value changes before and after treatment could be used as predictors of pathological response. Also, ADC value changes before and after treatment could be used as a tool to guide clinical decision-making.

Prevalence of nonalcoholic fatty liver disease in patients with hepatitis B: A meta-analysis.

BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with chronic hepatitis B (CHB) has increased in recent clinical practice; however, the relationship between CHB and hepatic steatosis (HS) remains controversial. AIM: To shed light on the potential association between NAFLD and hepatitis B virus (HBV) infection. METHODS: We conducted a systematic literature search using multiple databases, including PubMed, the Cochrane Library, Web of Science, and EMBASE, to identify relevant studies. Predefined inclusion criteria were used to determine the eligibility of the studies for further analysis. RESULTS: Comprehensive meta-analysis software was used for statistical analysis, which covered 20 studies. The results indicated a lower NAFLD susceptibility in HBV-infected individuals (pooled OR = 0.87; 95%CI = 0.69-1.08; I 2 = 91.1%), with diabetes (P = 0.015), body mass index (BMI; P = 0.010), and possibly age (P = 0.061) as heterogeneity sources. Of note, in four studies (6197 HBV patients), HBV-infected individuals had a reduced NAFLD risk (OR = 0.68, 95%CI = 0.51-0.89, P = 0.006). A positive link between hyperlipidemia and metabolic syndrome emerged in hepatitis B patients, along with specific biochemical indicators, including BMI, creatinine, uric acid, fasting blood glucose, and homeostasis model assessment of insulin resistance. CONCLUSION: HBV infection may provide protection against HS; however, the occurrence of HS in patients with HBV infection is associated with metabolic syndrome and specific biochemical parameters.

Comparative outcomes between cryopreserved cadaveric saphenous vein and spliced autogenous vein for infrainguinal bypass.

OBJECTIVE: Cryopreserved greater saphenous vein (CV) and spliced autogenous veins (SV) serve as alternative conduits for lower extremity revascularization when a single-segment autogenous saphenous vein is not available. This study compares the outcomes of infrainguinal bypasses using CV and two-segment SV as conduits. METHODS: We conducted a retrospective review of data on all lower extremity bypasses performed using CV or SV at our institution. Patients undergoing revascularization for atherosclerotic occlusive disease were included in the statistical analysis, while those with primary acute embolic and/or traumatic causes were excluded. Primary outcomes included limb loss. Secondary outcomes included primary, primary assisted, and secondary patency at one and 3 years. RESULTS: 56 patients were included in the analysis, 25 had CV bypass and 31 had SV. The groups did not significantly differ in demographics and comorbidities except for age (mean age 68 CV vs 62 SV, p = .03), and prior coronary artery bypass graft (32% CV vs 6.5% SV, p = .01). There was no statistically significant difference between CV and SV at one- and three-years in limb salvage (54.4% CV vs 61.7% SV, p = .96 and 48.3% CV vs 50.2% SV, p = .94), and bypass abandonment (44.2% CV vs 61.7% SV, p = .83 and 44.2% CV vs 44% SV, p = .85). Despite lower one and 3-year primary patency for CV compared to SV (33.3% CV vs 54.9% SV, p = .29, and 27.7% CV vs 48% SV, p = .27), the difference was statistically not significant. CV and SV had also similar one and 3-year primary assisted (41.8% CV vs 57.8% SV, p = .72 and 41.8% CV vs 44.9% SV, p = .71), and secondary patency (43.9% CV vs 61.7% SV, p = .8 and 43.9% CV vs 44% SV, p = .88), with no statistically significant difference. CONCLUSION: In patients for whom single-segment autologous saphenous vein bypass is not an option, CV and SV show comparable limb salvage up to 3 years. SV may be a more durable option with higher patency, this was however not statistically significant in our cohort likely due to sample size.

Spotlight on endoplasmic reticulum stress in acute kidney injury: A bibliometric analysis and visualization from 1997 to 2024.

BACKGROUND: Endoplasmic reticulum (ER) stress, a protective stress response of body and play important role in maintain ER stability. Acute kidney injury (AKI) is a severe syndrome, and the molecular mechanisms of AKI has not been fully elucidated. With an increasing understanding of ER stress, ER stress has been investigated and considered a potential and novel therapeutic target in AKI. This study aims to employ a bibliometric approach to analyze research trends and focal points in ER stress associated with AKI over 3 decades. METHODS: Data were retrieved from the Web of Science Core Collection on April 15, 2024. CiteSpace and VOSviewer bibliometric software were mainly used to measure bibliometrics and analyze knowledge graphs to predict the latest research trends in the field. RESULTS: There were 452 "ER stress in AKI" articles in the Web of Science Core Collection. According to the report, China and the United States were the leading research drivers in this field. Central South University was the most active academic institution, contributing the most documents. In this field, Dong Zheng was the most prolific author. The American Journal of Physiology-Renal Physiology was the journal with the most records among all journals. The keywords "NLRP3 inflammasome," "redox signaling," and novel forms of cell death such as "ferroptosis" may represent current research trends and directions. CONCLUSION: The bibliometric analysis comprehensively examines the trends and hotspots on "ER stress and AKI." Studies on AKI related to stress in the ER are still in their infancy. Research should focus on understanding the relationship between ER stress and inflammasome, redox signal pathways and new forms of cell death such as ferroptosis.

[Ultrasonographic features of Castleman disease in the head and neck: a report of 7 cases].

PURPOSE: To summarize the ultrasonographic features of head and neck Castleman disease (CD), and to clarify its diagnostic key points. METHODS: Seven patients with head and neck CD confirmed by histopathology were collected from Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. The clinical features and ultrasound findings of the patients were evaluated. RESULTS: Of the 7 patients (1 male and 6 females), the mean age at diagnosis was 31.4 years (7-60 years). All the cases were hyaline vascular type. On ultrasound, 3 lesions (42.9%) were located in the parotid gland, 4 lesions(57.1%) in the neck. All the lesions presented as a solitary, well-defined and solid mass without calcification. The echogenicity was markedly hypoechoic in 1 case(14.3%) and hypoechoic in 6 cases (85.7%). Of the 7 CD cases, 4 cases (57.1%) were heterogeneous masses with linear echogenic septa. All lesions had mixed pattern in vascularity on color Doppler sonography. CONCLUSIONS: Most CDs in the head and neck represent as a markedly hypoechoic or hypoechoic lesion with mixed pattern in vascularity. The neoplasm may be characterized by the presence of linear echogenic septa within the mass.

A short-term functional recovery comparison of therapeutic plasma exchange and immunoadsorption in severe acute neuroimmune diseases.

OBJECTIVE: To compare the differential impact of recombinant protein A immunoadsorption (PAIA) or therapeutic plasma exchange (TPE) on neurological functional improvement and quality of life in patients afflicted with severe acute neuroimmune diseases, including Guillain-Barré syndrome (GBS), myasthenia gravis (MG), neuromyelitis optica spectrum disorder (NMOSD), and anti-NMDA receptor encephalitis (NMDARE). METHODS: The retrospective study included 29 patients with moderate to severe disability (modified Rankin scale, mRS≥3) due to acute neuroimmune diseases at the second Xiangya hospital from January 2021 to January 2023. The clinical efficacy of PAIA and TPE in improving neurological function (ΔmRS≥1) and the difference in favorable functional outcomes (mRS 0-2) at three months were evaluated. The impact of both treatments on patients' health-related quality of life (HRQoL) was assessed using a visual analog scale (EQ-VAS) score ranging from 0 to 100. RESULTS: The findings revealed that the PAIA group exhibited a significantly higher rate of improvement in modified Rankin scale (mRS) scores (ΔmRS≥1) at the three-month follow-up compared to the TPE group (94.4 % vs. 54.5 %, p = 0.018). However, no statistically significant difference was observed between the two treatment modalities in terms of favorable neurological functional outcomes at the three-month mark. Furthermore, the PAIA group demonstrated a significantly higher EQ-VAS score at 14 days post-treatment compared to the TPE group (60.0 vs. 47.7, p = 0.017). CONCLUSION: In the short-term management of severe acute neuroimmune diseases, PAIA may present a greater probability of improving neurological function and facilitating an earlier enhancement of quality of life compared to TPE.

Extraction and characterization of novel Prosopis Juliflora bark and Boehmeria nivea fibre for use as reinforcement in the hybrid composites with the effect of curing temperature, fibre length and weight percentages.

The hybrid composite sample based on Prosopis Juliflora (PJ) bark and ramie fibre with different length, weight percentage, and curing temperature were created for the first time in this work. Totally, 120 hybrid composite samples were tested in this study. There were five different fibre lengths: 10 mm, 15 mm, 20 mm, 25 mm, and 30 mm, weight percentages 10 %, 20 %, 30 %, 40 %, and 50 %, and different curing temperatures 80 °C, 90 °C, 100 °C, 110 °C, and 120 °C used to produce the hybrid composite samples. Due to the cross-linking ability with the epoxy matrix, the hybrid composite specimen shows high resistance up to 98 Shore D hardness. The high polarity of the epoxy matrix and the hydrogen bond strengthening effect, increased the composite sample flexural strength by 12 %. The curing temperature of 100 °C, 20 mm fibre length, and 30 % of the hybrid composite sample achieved the highest tensile strength (28.76 MPa), flexural strength (46.54 MPa), impact strength (4.5 J), and hardness strength properties (98 shore D). Thermo gravimetric analysis (TGA) revealed the composite samples initial decomposition temperature (Ti) at 98 °C, maximum decomposition temperature (Tmax) at 320 °C, and the final decomposition temperature (Tf) at 466 °C.

Preclinical characterization of [18F]D2-LW223: an improved metabolically stable PET tracer for imaging the translocator protein 18 kDa (TSPO) in neuroinflammatory rodent models and non-human primates.

Positron emission tomography (PET) targeting translocator protein 18 kDa (TSPO) can be used for the noninvasive detection of neuroinflammation. Improved in vivo stability of a TSPO tracer is beneficial for minimizing the potential confounding effects of radiometabolites. Deuteration represents an important strategy for improving the pharmacokinetics and stability of existing drug molecules in the plasma. This study developed a novel tracer via the deuteration of [18F]LW223 and evaluated its in vivo stability and specific binding in neuroinflammatory rodent models and nonhuman primate (NHP) brains. Compared with LW223, D2-LW223 exhibited improved binding affinity to TSPO. Compared with [18F]LW223, [18F]D2-LW223 has superior physicochemical properties and favorable brain kinetics, with enhanced metabolic stability and reduced defluorination. Preclinical investigations in rodent models of LPS-induced neuroinflammation and cerebral ischemia revealed specific [18F]D2-LW223 binding to TSPO in regions affected by neuroinflammation. Two-tissue compartment model analyses provided excellent model fits and allowed the quantitative mapping of TSPO across the NHP brain. These results indicate that [18F]D2-LW223 holds significant promise for the precise quantification of TSPO expression in neuroinflammatory pathologies of the brain.

Enabling Universal Access to Rapid and Stable Tetrazine Bioorthogonal Probes through Triazolyl-Tetrazine Formation.

Despite the immense potential of tetrazine bioorthogonal chemistry in biomedical research, the in vivo performance of tetrazine probes is challenged by the inverse correlation between the physiological stability and reactivity of tetrazines. Additionally, the synthesis of functionalized tetrazines is often complex and requires specialized reagents. To overcome these issues, we present a novel tetrazine scaffold-triazolyl-tetrazine-that can be readily synthesized from shelf-stable ethynyl-tetrazines and azides. Triazolyl-tetrazines exhibit improved physiological stability along with high reactivity. We showcase the effectiveness of this approach by creating cell-permeable probes for protein labeling and live cell imaging, as well as efficiently producing 18F-labeled molecular probes for positron emission tomography imaging. By utilizing the readily available pool of functionalized azides, we envisage that this modular approach will provide universal accessibility to tetrazine bioorthogonal tools, facilitating applications in biomedicine and materials science.

Whole-brain inputs and outputs of Phox2b and GABAergic neurons in the nucleus tractus solitarii.

The nucleus tractus solitarii (NTS) plays a critical role in the homeostatic regulation of respiration, blood pressure, sodium consumption and metabolic processes. Despite their significance, the circuitry mechanisms facilitating these diverse physiological functions remain incompletely understood. In this study, we present a whole-brain mapping of both the afferent and efferent connections of Phox2b-expressing and GABAergic neurons within the NTS. Our findings reveal that these neuronal populations not only receive monosynaptic inputs primarily from the medulla oblongata, pons, midbrain, supra-midbrain and cortical areas, but also mutually project their axons to these same locales. Moreover, intense monosynaptic inputs are received from the central amygdala, the paraventricular nucleus of the hypothalamus, the parasubthalamic nucleus and the intermediate reticular nucleus, along with brainstem nuclei explicitly engaged in respiratory regulation. In contrast, both neuronal groups extensively innervate brainstem nuclei associated with respiratory functions, although their projections to regions above the midbrain are comparatively limited. These anatomical findings provide a foundational platform for delineating an anatomical framework essential for dissecting the specific functional mechanisms of these circuits.

Elucidating the Phytochemical Landscape of Leaves, Stems, and Tubers of Codonopsis convolvulacea through Integrated Metabolomics.

Codonopsis convolvulacea is a highly valued Chinese medicinal plant containing diverse bioactive compounds. While roots/tubers have been the main medicinal parts used in practice, leaves and stems may also harbor valuable phytochemicals. However, research comparing volatiles across tissues is lacking. This study performed metabolomic profiling of leaves, stems, and tubers of C. convolvulacea to elucidate tissue-specific accumulation patterns of volatile metabolites. Ultra-high performance liquid chromatography-tandem mass spectrometry identified 302 compounds, belonging to 14 classes. Multivariate analysis clearly differentiated the metabolic profiles of the three tissues. Numerous differentially accumulated metabolites (DAMs) were detected, especially terpenoids and esters. The leaves contained more terpenoids, ester, and alcohol. The stems accumulated higher levels of terpenoids, heterocyclics, and alkaloids with pharmaceutical potential. The tubers were enriched with carbohydrates like sugars and starch, befitting their storage role, but still retained reasonable amounts of valuable volatiles. The characterization of tissue-specific metabolic signatures provides a foundation for the selective utilization of C. convolvulacea parts. Key metabolites identified include niacinamide, p-cymene, tridecanal, benzeneacetic acid, benzene, and carveol. Leaves, stems, and tubers could be targeted for antioxidants, drug development, and tonics/nutraceuticals, respectively. The metabolomic insights can also guide breeding strategies to enhance the bioactive compound content in specific tissues. This study demonstrates the value of tissue-specific metabolite profiling for informing the phytochemical exploitation and genetic improvement of medicinal plants.