Acorus tatarinowii oils exert protective effects on microglia-mediated inflammatory injury via restoring gut microbiota composition in experimental stroke rats.

Growing evidence has demonstrated that gut microbiota could be developed as a therapeutic target due to its contribution to microglia activation in the pathological process of ischemic stroke. Acorus tatarinowii oils (AT oils), which is considered as the active fraction of a traditional Chinese herbal medicine Acorus tatarinowii, exerts various bioactivities and prebiotic effects. However, it remains unclear that the effect of AT oils on inflammatory response after ischemic stroke and whether its underlying mechanism is associated to gut microbiota and the intestinal barrier. In the current study, we aim to investigate the anti-microglial neuroinflammation mechanism of AT oils in a middle cerebral artery occlusion model of ischemic stroke. The compositions of AT oils were identified by GC-MS. Our results demonstrated that AT oils could effectively relieve cerebral infarction, inhibit neuronal apoptosis, degrade the release of pro-inflammatory factors (TNF-α, IL-17, IL-6 and IFN-γ), and mediate the polarization of microglia. Moreover, AT oils restored the composition and the balance of gut microbiota in stroke rats, and reduced abundance of opportunistic genera including Verrucomicrobia, Akkermansia and Tenericutes, as well as increased beneficial bacteria abundance such as Tenericutes and Prevotella_copri. To investigate the role of gut microbiota on AT oils against ischemic stroke, we conducted the fecal microbiota transplantation (FMT) experiments with gut microbiota consumption, which suggested that the depletion of gut microbiota took away the protective effect of AT oils, confirming the importance of gut microbiota in the protective effect of AT oils on ischemic stroke. FMT experiments have demonstrated that AT oils preserved the gut permeability and blood-brain barrier, as well as mediated the microglial phenotype under the intervention of gut microbiota. In summary, AT oils could efficaciously moderate neuronal damage and intervene microglial phenotype by reversing gut microbiota disorder in ischemic stroke rats.

Theoretical study on degradation of polymethyl substituted benzenes by OH radicals in the atmosphere.

As volatile organic compounds (VOCs), pentamethylbenzene (5-PeMB) and hexamethylbenzene (6-HeMB) are found widely in petroleum and coal tar. Through combustion and industrial generation entering into the atmosphere, they can produce photochemical smog and secondary organic aerosols (SOA) to endanger human health and ecoenvironment eventually. In order to reveal their environmental chemistry, the OH-initiated degradation mechanisms of 5-PeMB and 6-HeMB were studied based on density functional theory (DFT). Result showed that addition pathways were the most favorable with energy barriers of 20.7 and 25.3 kJ/mol, respectively, in the two reactions. The degradation rate constants at 298 K were calculated to be 2.69 × 10-10 and 1.28 × 10-10 cm3 molecule-1 ·s-1, coinciding with the available experimental values. In the presence of OH radicals, the atmospheric lifetimes were estimated to be 2.17 and 2.78 h, respectively, for 5-PeMB and 6-HeMB. According to the quantitative structure-activity relationship (QSAR) model, the toxicity during the degradation process is decreased to fish, daphnia, and green algae.

Association between chronic obstructive pulmonary disease and 28-day mortality in patients with sepsis: a retrospective study based on the MIMIC-III database.

BACKGROUND: Sepsis is a common cause of mortality in critically ill patients, and chronic obstructive pulmonary disease (COPD) is one of the most common comorbidities in septic patients. However, the impact of COPD on patients with sepsis remained unclear. Therefore, the purpose of this study aimed to assess the effect of COPD on the prognosis of septic patients based on Medical Information Mart for Intensive Care (MIMIC-III) database. METHODS: In this retrospective study based on the (MIMIC)-III database version 1.4 (v1.4), we collected clinical data and 28-day all-cause mortality from patients with sepsis in intensive care unit (ICU) and these patients met the diagnostic criteria of Sepsis 3 on ICU admission between 2008 and 2012. International Classification of Diseases (ICD-9) (4660, 490, 4910, 4911, 49120, 49121, 4918, 4919, 4920, 4928, 494, 4940, 4941, 496) was used to identified COPD. We applied Kaplan-Meier analysis to compare difference of 28-day all-cause mortality between septic patients with and without COPD. Cox proportional-hazards model was applied to explore the risk factor associated with 28-day all-cause mortality in patients with sepsis. RESULTS: Six thousand two hundred fifty seven patients with sepsis were included in this study, including 955 (15.3%) patients with COPD and 5302 patients without COPD (84.7%). Compared with patients without COPD, patients with COPD were older (median: 73.5 [64.4, 82.0] vs 65.8 [52.9, 79.1], P < 0.001), had higher simplified acute physiology score II (SAPSII) (median: 40.0 [33.0, 49.0] vs 38.0 [29.0,47.0], P < 0.001) and greater proportion of mechanical ventilatory support (MV) (55.0% vs 48.9%, P = 0.001). In our study, septic patients with COPD had higher 28-day all-cause mortality (23.6% vs 16.4%, P < 0.001) than patients without COPD. After adjusting for covariates, the results showed that COPD was an independent risk factor for the 28-day all-cause mortality of patients with sepsis (HR 1.30, 95%CI: 1.12-1.50, P = 0.001). CONCLUSIONS: COPD was an independent risk factor of 28-day all-cause mortality in septic patients. Clinically, septic patients with COPD should be given additional care.

Exploring the therapeutic potential of natural compounds for Alzheimer's disease: Mechanisms of action and pharmacological properties.

Alzheimer's Disease (AD) is a global public health priority characterized by high mortality rates in adults and an increasing prevalence in aging populations worldwide. Despite significant advancements in comprehending the pathogenesis of AD since its initial report in 1907, there remains a lack of effective curative or preventive measures for the disease. In recent years, natural compounds sourced from diverse origins have garnered considerable attention as potential therapeutic agents for AD, owing to their anti-inflammatory, antioxidant, and neuroprotective properties. This review aims to consolidate the therapeutic effects of natural compounds on AD, specifically targeting the reduction of ß-amyloid (Aß) overproduction, anti-apoptosis, autophagy, neuroinflammation, oxidative stress, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction. Notably, the identified compounds exhibiting these effects predominantly originate from plants. This review provides valuable insights into the potential of natural compounds as a reservoir of novel therapeutic agents for AD, thereby stimulating further research and contributing to the development of efficacious treatments for this devastating disease.

Advances and applications of machine learning and deep learning in environmental ecology and health.

Machine learning (ML) and deep learning (DL) possess excellent advantages in data analysis (e.g., feature extraction, clustering, classification, regression, image recognition and prediction) and risk assessment and management in environmental ecology and health (EEH). Considering the rapid growth and increasing complexity of data in EEH, it is of significance to summarize recent advances and applications of ML and DL in EEH. This review summarized the basic processes and fundamental algorithms of the ML and DL modeling, and indicated the urgent needs of ML and DL in EEH. Recent research hotspots such as environmental ecology and restoration, environmental fate of new pollutants, chemical exposures and risks, chemical hazard identification and control were highlighted. Various applications of ML and DL in EEH demonstrate their versatility and technological revolution, and present some challenges. The perspective of ML and DL in EEH were further outlined to promote the innovative analysis and cultivation of the ML-driven research paradigm.

Estimated glomerular filtration rate partially recovered in patients without Hypertriglyceridemia during Tenofovir disoproxil fumarate treatment.

BACKGROUND: Decrease in estimated glomerular filtration rate (eGFR) during Tenofovir disoproxil fumarate (TDF) treatment remains a concern, and few patients experience partial recovery of eGFR. This study aimed to investigate the risk factors for eGFR recovery in patients with and without hypertriglyceridemia. METHODS: A total of 203 patients with chronic HBV infection were prospectively recruited and followed up for three years. Data were collected at baseline, first, second, and third years during TDF treatment. RESULTS: Most patients achieved normal ALT (80.0% vs. 82.5%) and undetectable HBV DNA (95.0% vs. 95.6%) in both groups (p > 0.05). For patients with hypertriglyceridemia, eGFR and cholesterol did not change significantly during the 3-year follow-up, while triglyceride (TG) decreased significantly in the first year and persisted at a lower level in the subsequent two years. For patients without hypertriglyceridemia, eGFR declined significantly in the first year of treatment, then gradually recovered during the subsequent two years, and eGFR was negatively correlated with TG at the four time points. Fifteen (15/183, 8.2%) patients without hypertriglyceridemia experienced eGFR partial recovery in the third year. Univariate and multivariate analyses showed that baseline eGFR <90 mL/(min·1.73 m2) (p < 0.01; 95% CI: 0.019-0.284) and age (p < 0.01; 95% CI: 0.817-0.960) were independent risk factors for eGFR recovery. CONCLUSION: eGFR partially recovered in patients without hypertriglyceridemia during TDF treatment, and TG regulation might be a useful strategy to hinder renal function decline, although larger, confirmatory studies are necessary to validate our findings.Key messagesFor patients with normal triglyceride, eGFR declined significantly at the first year of TDF treatment, then gradually recovered during the subsequent two years, and eGFR was negatively correlated with TG. Baseline eGFR <90 mL/(min·1.73 m2) and age were independent risk factors for eGFR recovery.

Bushen-Yizhi formula exerts neuroprotective effect via inhibiting excessive mitophagy in rats with chronic cerebral hypoperfusion.

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen-Yizhi formula (BSYZ), a traditional Chinese medicine (TCM) prescription widely used in treating mental retardation and neurodegenerative diseases with kidney deficiency, has been reported to attenuate oxidative stress-related neuronal apoptosis. Chronic cerebral hypoperfusion (CCH) is considered to be related to cognitive and emotional disorders. However, it remains to be clarified that the effect of BSYZ on CCH and its underlying mechanism. AIM OF THE STUDY: In the present study, we aimed to investigate the therapeutic effects and underlying mechanisms of BSYZ on CCH- injured rats based on the domination of oxidative stress balance and mitochondrial homeostasis through inhibiting abnormal excessive mitophagy. MATERIALS AND METHODS: The in vivo rat model of CCH was established by bilateral common carotid artery occlusion (BCCAo), while the in vitro PC12 cell model was exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) condition, and a mitophagy inhibitor (chloroquine) by decreasing autophagosome-lysosome fusion was used as reverse validation in vitro. The protective role of BSYZ on CCH-injured rats was measured by open field test, morris water maze test, analysis of amyloid fibrils and apoptosis, and oxidative stress kit. The expression of mitochondria-related and mitophagy-related proteins was evaluated by Western blot, immunofluorescence, JC-1 staining assay and Mito-Tracker Red CMXRos assay. The components of BSYZ extracts were identified by HPLC-MS. The molecular docking studies were used to investigate the potential interactions of characteristic compounds in BSYZ with lysosomal membrane protein 1 (LAMP1). RESULTS: Our result indicated that BSYZ improved the cognition and memory abilities of the BCCAo rats by diminishing the occurrence of apoptosis and abnormal amyloid deposition accumulation, suppressing oxidative stress damage for abnormal excessive mitophagy activation in the hippocampus. Moreover, in OGD/R-damaged PC12 cells, BSYZ drug serum treatment substantially enhanced the PC12 cell viability and suppressed intracellular reactive oxygen species (ROS) accumulation for protecting against oxidative stress, along with the improvement of mitochondrial membrane activity and lysosomal proteins. Our studies also showed that inhibiting of autophagosome-lysosome fusion to generate autolysosomes by using chloroquine abrogated the neuroprotective effects of BSYZ on PC12 cells regarding the modulation of antioxidant defence and mitochondrial membrane activity. Furthermore, the molecular docking studies supported the direct bindings between lysosomal associated membrane protein 1 (LAMP1) and compounds in BSYZ extract to inhibit excessive mitophagy. CONCLUSION: Our study demonstrated that BSYZ played a neuroprotective role in rats with CCH and reduced neuronal oxidative stress via promoting the formation of autolysosomes to inhibit abnormal excessive mitophagy.

The Interplay between Meningeal Lymphatic Vessels and Neuroinflammation in Neurodegenerative Diseases.

Meningeal lymphatic vessels (MLVs) are essential for the drainage of cerebrospinal fluid, macromolecules, and immune cells in the central nervous system. They play critical roles in modulating neuroinflammation in neurodegenerative diseases. Dysfunctional MLVs have been demonstrated to increase neuroinflammation by horizontally blocking the drainage of neurotoxic proteins to the peripheral lymph nodes. Conversely, MLVs protect against neuroinflammation by preventing immune cells from becoming fully encephalitogenic. Furthermore, evidence suggests that neuroinflammation affects the structure and function of MLVs, causing vascular anomalies and angiogenesis. Although this field is still in its infancy, the strong link between MLVs and neuroinflammation has emerged as a potential target for slowing the progression of neurodegenerative diseases. This review provides a brief history of the discovery of MLVs, introduces in vivo and in vitro MLV models, highlights the molecular mechanisms through which MLVs contribute to and protect against neuroinflammation, and discusses the potential impact of neuroinflammation on MLVs, focusing on recent progress in neurodegenerative diseases.

Dynamic changes of estimated glomerular filtration rate are conversely related to triglyceride in non-overweight patients.

BACKGROUND: Correlation between Triglyceride (TG) and estimated glomerular filtration rate (eGFR) remains largely unknown in overweight and non-overweight patients. AIM: To investigated the dynamic changes of eGFR and lipid profiles during 3-year tenofovir disoproxil fumarate (TDF) treatment in patients with chronic hepatitis B (CHB) and overweight. METHODS: A total of 202 CHB patients who received TDF treatment at the Third People's Hospital of Changzhou (Changzhou, China) and Nanjing Drum Tower Hospital (Nanjing, China) between January 2016 and May 2018 were retrospectively enrolled. According to the body mass index (BMI) at the initiation of TDF treatment, CHB patients were divided into overweight (BMI ≥ 25 kg/m2) and non-overweight (BMI < 25 kg/m2) groups. Logistic regression was applied for the analysis of risk factors for eGFR < 90 mL/(min·1.73 m2). RESULTS: There is no significant difference in hepatitis B virus DNA (HBV DNA) negativity and hepatitis Be antigen (HBeAg) loss between patients with overweight and non-overweight (both P > 0.05). More patients in non-overweight group achieved alanine aminotransferase normalization compared with those in overweight group (χ 2 = 11.036, P < 0.01). In non-overweight patients, the eGFR significantly declined in the 1st year (P < 0.01), then remained at a relatively lower level. TG significantly declined in the 2nd year (P = 0.02) and increased in the 3rd year. Moreover, TG was negatively correlated with GFR at the four-time points (P = 0.002, 0.030, 0.007, 0.008, respectively). In overweight patients, eGFR and TG remained relatively stable during the 3-year treatment, and eGFR showed no significant relationship with TG. Moreover, multivariate analysis showed that age [P < 0.01, 95%CI (0.97-1.005)] and baseline eGFR [P < 0.01, 95%CI (5.056-33.668)] were independent risk factors for eGFR < 90 mL/(min·1.73 m2) at the 3rd year. CONCLUSION: Dynamic changes in renal function were conversely related to TG during TDF treatment in patients with CHB and normal BMI, but not with overweight.

Application of Solution Method to Prepare High Performance Multicomponent Oxide Thin Films.

Capacitors play an increasingly important role in hybrid integrated circuits, while the MIM capacitors with high capacitance density and small thickness can meet the needs of high integration. Generally speaking, the films prepared with a single metal oxide dielectric often achieve a breakthrough in one aspect of performance, but dielectric layers are required to be improved to get better performance in leakage current, capacitance density, and transmittance simultaneously in modern electronic devices. Therefore, we optimized the performance of the dielectric layers by using multiple metal oxides. We combined zirconia, yttria, magnesium oxide, alumina, and hafnium oxide with the solution method to find the best combination of these five metal oxides. The physical properties of the multi-component films were measured by atomic force microscopy (AFM), ultraviolet-visible spectrophotometer, and other instruments. The results show that the films prepared by multi-component metal oxides have good transmittance and low roughness. The thicknesses of all films in our experiment are less than 100 nm. Then, metal-insulator-metal (MIM) devices were fabricated. In addition, we characterized the electrical properties of MIM devices. We find that multi-component oxide films can achieve good performances in several aspects. The aluminum-magnesium-yttrium-zirconium-oxide (AMYZOx) group of 0.6 M has the lowest leakage current density, which is 5.03 × 10-8 A/cm2 @ 1.0 MV/cm. The hafnium-magnesium-yttrium-zirconium-oxide (HMYZOx) group of 0.8 M has a maximum capacitance density of 208 nF/cm2. The films with a small thickness and a high capacitance density are very conducive to high integration. Therefore, we believe that multi-component films have potential in the process of dielectric layers and great application prospects in highly integrated electronic devices.

Investigations on mechanisms, kinetics, and ecotoxicity in OH-initiated degradation of 1,2,4,5-tetramethylbenzene in the environment.

As one of the volatile organic compounds (VOCs) in the environment, 1,2,4,5-tetramethylbenzene (1,2,4,5-TeMB) present in oily wastewater, and it can occur substitution, abstraction, and addition reactions with OH radicals in the atmosphere and wastewater. Electrostatic potential (ESP) and average local ionization energy (ALIE) prediction indicate that H atoms from CH3 group and the benzene ring are the most active sites in 1,2,4,5-TeMB. The result shows that potential energy surfaces (PESs) in the gas and aqueous phase are similar, and the relevant barriers in the latter one are higher. The dominant channel is H abstraction from the benzene ring, and the subdominant one is OH radical addition to the benzene ring. Furthermore, subsequent reactions of dominant products with O2, NO2, NO, and OH radicals in the atmosphere are studied, as well. The total reaction rate constant is calculated to be 2.36×10-10 cm3 molecule-1 s-1 at 1 atm and 298 K in the atmosphere, which agrees well with the experimental data. While the total rate constant in the aqueous phase is much lower than that in the gas phase. Ecologic toxicity analysis shows that 1,2,4,5-TeMB is very toxic to fish, daphnia, and green algae; and OH-initiated degradation in the environment will reduce its toxicity.

Application of Amorphous Zirconium-Yttrium-Aluminum-Magnesium-Oxide Thin Film with a High Relative Dielectric Constant Prepared by Spin-Coating.

Amorphous metal oxide has been a popular choice for thin film material in recent years due to its high uniformity. The dielectric layer is one of the core materials of the thin film transistor (TFT), and it affects the ability of charges storage in TFT. There is a conflict between a high relative dielectric constant and a wide band gap, so we solved this problem by using multiple metals to increase the entropy of the system. In this paper, we prepared zirconium-yttrium-aluminum-magnesium-oxide (ZYAMO) dielectric layers with a high relative dielectric constant using the solution method. The basic properties of ZYAMO films were measured by an atomic force microscope (AFM), an ultraviolet-visible spectrophotometer (UV-VIS), etc. It was observed that ZYAMO thin films had a larger optical band when the annealing temperature increased. Then, metal-insulator-metal (MIM) devices were fabricated to measure the electrical properties. We found that the leakage current density of the device is relatively lower and the ZYAMO thin film had a higher relative dielectric constant as the concentration went up. Finally, it reached a high relative dielectric constant of 56.09, while the leakage current density was no higher than 1.63 × 10-6 A/cm2@ 0.5 MV/cm at 1.0 M and 400 °C. Therefore, the amorphous ZYAMO thin films has a great application in the field of high permittivity request devices in the future.

catena-Poly[[[tetra-aqua-cadmium(II)]-µ-4,4'-bipyridine] fumarate tetra-hydrate].

In the crystal structure of the title compound, [Cd(C(10)H(8)N(2))(H(2)O)(4)](C(4)H(2)O(4))·4H(2)O, the Cd(II) atom, on an inversion centre, is six-coordinated by four O atoms from four water mol-ecules and two N atoms from 4,4'-bpy mol-ecules in a distorted octa-hedral coordination geometry. Weak C-H⋯O inter-actions between uncoordinated carboxyl-ate O atoms of fumaric acid and water mol-ecules contribute to the crystal packing stability.