Repetitive transcranial magnetic stimulation in Alzheimer's disease: effects on neural and synaptic rehabilitation.

Alzheimer's disease is a neurodegenerative disease resulting from deficits in synaptic transmission and homeostasis. The Alzheimer's disease brain tends to be hyperexcitable and hypersynchronized, thereby causing neurodegeneration and ultimately disrupting the operational abilities in daily life, leaving patients incapacitated. Repetitive transcranial magnetic stimulation is a cost-effective, neuro-modulatory technique used for multiple neurological conditions. Over the past two decades, it has been widely used to predict cognitive decline; identify pathophysiological markers; promote neuroplasticity; and assess brain excitability, plasticity, and connectivity. It has also been applied to patients with dementia, because it can yield facilitatory effects on cognition and promote brain recovery after a neurological insult. However, its therapeutic effectiveness at the molecular and synaptic levels has not been elucidated because of a limited number of studies. This study aimed to characterize the neurobiological changes following repetitive transcranial magnetic stimulation treatment, evaluate its effects on synaptic plasticity, and identify the associated mechanisms. This review essentially focuses on changes in the pathology, amyloidogenesis, and clearance pathways, given that amyloid deposition is a major hypothesis in the pathogenesis of Alzheimer's disease. Apoptotic mechanisms associated with repetitive transcranial magnetic stimulation procedures and different pathways mediating gene transcription, which are closely related to the neural regeneration process, are also highlighted. Finally, we discuss the outcomes of animal studies in which neuroplasticity is modulated and assessed at the structural and functional levels by using repetitive transcranial magnetic stimulation, with the aim to highlight future directions for better clinical translations.

Surgical Correction of Orbital Hypertelorism With Absorbable Plate Instead of Frontal and Orbital Bar and Inverted U-Shaped Osteotomy.

OBJECTIVE: The aim of the study is to investigate the effect and feasibility of using absorbable plate instead of frontal and orbital bar and inverted U-shaped osteotomy to correct the widening of orbital distance. METHODS: The surgical effect and feasibility of using absorbable plate instead of frontal and orbital bridge plus inverted U-osteotomy for orbital widening syndrome in seven cases between January 2019 and February 2022 were retrospectively analyzed. First, the surgical procedure for orbital hypertelorism was inverted U-shaped orbital osteotomy, and a frontal bone flap was removed, exposing the superior orbital margin and the orbital circumference, and the orbital bone was directly cut off by inverted U-shaped osteotomy. The widened bone in the middle of the orbit was removed, and a long absorbable plate was used to replace the orbitofrontal bridge. The two sides of the orbit were fixed on the absorbable plate, and the absorbable plate was fixed on the rear skull. The clinical effect of treatment, complications (such as cerebrospinal fluid leakage and infection), safety, and feasibility of surgery were evaluated. RESULTS: Using absorbable plate instead of fronto-orbital bridge achieved the effect of orbitofrontal bridge, without orbital distance widening, cerebrospinal fluid leakage, and intracranial infection. Operating time was reduced. There was no metal fixation, and there was no risk of a second operation. CONCLUSIONS: The effect of replacing the frontal-orbital bridge with an absorbable plate and inverted U-shaped osteotomy is positive, the operation time is short, and the orbital distance is clearly improved. This approach can replace the traditional orbital-distance operation, and the incidence of postoperative cerebrospinal fluid leakage and infection is low. Long-term follow-up results are stable.

Dietary effects of vitamin C on antioxidant capacity, intestinal microbiota and the resistance of pathogenic bacteria in cultured Silver pomfret (Pampus argenteus).

As most teleosts are unable to synthesize vitamin C, supplemental diets containing vitamin C diets play a crucial role in fish health. The aim of this study was to investigate the effect of dietary vitamin C on the intestinal enzyme activity and intestinal microbiota of silver pomfre (Pampus argenteus). Four experimental diets were supplemented with basic diets containing 300 mg of vitamin C/kg (group tjl3), 600 mg of vitamin C/kg (group tjl6), and 1200 mg of vitamin C/kg (group tjl12), as well as vitamin C-free supplemental basic diet (group tjl0), respectively. The four diets were fed to juvenile P. argenteus (average initial weight: 4.68 ± 0.93 g) for 6 weeks. The results showed that the activity of SOD (superoxide dismutase) and CAT (catalase) increased significantly while that of MDA (malondialdehyde) decreased significantly in group tjl3 compared to vitamin group tjl0. At the genus level, groups tjl0, tjl6, and tjl12 contained the same dominant microbial community, Stenotrophomonas, Photobacterium, and Vibrio, whereas group tjl3 was dominated by Stenotrophomonas, Delftia, and Bacteroides. Among the fish fed with a basic diet containing 300 mg of vitamin C/kg, the intestines exhibited a notable abundance of probiotic bacteria, including lactic acid bacteria (Lactobacillus) and Bacillus. The abundance of Aeromonas in groups tjl3 and tjl6 was lower than that of the vitamin C-free supplemental basic diet group, whereas Aeromonas was not detected in group tjl12. In addition, a causative agent of the disease outbreak in cultured P. argenteus, Photobacterium damselae subsp. Damselae (PDD) was the dominant microbiota community in groups tjl0, tjl6 and tjl12, whereas the abundance of PDD in group tjl3 was the lowest among the diets. Taken together, the diets supplied with vitamin C could influence the composition microbial community of P. argenteus. The low level of vitamin C (300 mg of vitamin C/kg per basic diet) supplementation could not only improve the antioxidant capacity but also resist the invasion of pathogenic bacteria.

Statistical comparison for assessing agreement between two mass spectrometric methods for the analysis of polychlorinated dibenzo-p-dioxins and furans (PCDDs/Fs)i n contaminated soils.

A gas chromatography coupled to high-resolution mass spectrometry (GC-HR/MS) has been used as the standard method for the quantification of polychlorinated dibenzo-p-dioxins and furans (PCDDs/Fs), which are regulated at screening and action levels in the environment. However, several alternative methods have been attempted due to the disadvantage of its high cost. Although a gas chromatography with triple quadrupole mass spectrometry (GC-QqQ-MS/MS) has been used in a wide variety of sample matrices, showing that they are interchangeable, there has been a lack of comprehensive studies on statistical agreement with GC-HR/MS. In this study, a pairwise comparison of the total concentrations of PCDDs/Fs in 90 soil field samples obtained by two mass spectrometric methods was performed using the Passing-Bablok (P&B) regression and Bland-Altman (B&A) analysis for the method comparison. According to the result of the B&A analysis, the concentration range of PCDDs/Fs was between 98.2 and 1760 pg/g showed good agreement between two methods at the 95 % confidence level (CL). Although there was a large discrepancy between the two methods in the low concentrations (< 16.5 pg/g of PCDDs/Fs), this result was similar to the P&B regression analysis. As the verification results by B&A and P&B regression analysis, the interchangeable concentration range between the two methods was confirmed to be adequate for the monitoring of PCDDs/Fs regulating levels in soils.

BCAT1 alleviates early brain injury by inhibiting ferroptosis through PI3K/AKT/mTOR/GPX4 pathway after subarachnoid hemorrhage.

Regulation of the redox system by branched-chain amino acid transferase 1 (BCAT1) is of great significance in the occurrence and development of diseases, but the relationship between BCAT1 and subarachnoid hemorrhage (SAH) is still unknown. Ferroptosis, featured by iron-dependent lipid peroxidation accompanied by the depletion of glutathione peroxidase 4 (GPX4), has been implicated in the pathological process of early brain injury after subarachnoid hemorrhage. This study established SAH model by endovascular perforation and adding oxyhemoglobin (Hb) to HT22 cells and delved into the mechanism of BCAT1 in SAH-induced ferroptotic neuronal cell death. It was found that SAH-induced neuronal ferroptosis could be inhibited by BCAT1 overexpression (OE) in rats and HT22 cells, and BCAT1 OE alleviated neurological deficits and cognitive dysfunction in rats after SAH. In addition, the effect of BCAT1 could be reversed by the Ly294002, a specific inhibitor of the PI3K pathway. In summary, our present study indicated that BCAT1 OE alleviated early brain injury EBI after SAH by inhibiting neuron ferroptosis via activation of PI3K/AKT/mTOR pathway and the elevation of GPX4. These results suggested that BCAT1 was a promising therapeutic target for subarachnoid hemorrhage.

Ultrasonic treatment of endocrine disrupting compounds, pharmaceuticals, and personal care products in water: An updated review.

Pharmaceuticals, personal care products (PPCPs), and endocrine-disrupting compounds (EDCs) have seen a recent sustained increase in usage, leading to increasing discharge and accumulation in wastewater. Conventional water treatment and disinfection processes are somewhat limited in effectively addressing this micropollutant issue. Ultrasonication (US), which serves as an advanced oxidation process, is based on the principle of ultrasound irradiation, exposing water to high-frequency waves, inducing thermal decomposition of H2O while using the produced radicals to oxidize and break down dissolved contaminants. This review evaluates research over the past five years on US-based technologies for the effective degradation of EDCs and PPCPs in water and assesses various factors that can influence the removal rate: solution pH, temperature of water, presence of background common ions, natural organic matter, species that serve as promoters and scavengers, and variations in US conditions (e.g., frequency, power density, and reaction type). This review also discusses various types of carbon/non-carbon catalysts, O3 and ultraviolet processes that can further enhance the degradation efficiency of EDCs and PPCPs in combination with US processes. Furthermore, numerous types of EDCs and PPCPs and recent research trends for these organic contaminants are considered.

A rapid on-site visualization platform based on RPA coupled with CRISPR-Cas12a for the detection of genetically modified papaya 'Huanong No.1'.

The Papaya ringspot virus (PRSV)-resistant genetically modified (GM) papaya 'Huanong No.1' has been certified as safe for consumption and widely planted in China for about 18 years. To protect consumers' rights and facilitate government supervision and monitoring, it is necessary to establish a simple, rapid, and specific detection method for 'Huanong No.1'. Herein, we developed a platform based on recombinase polymerase amplification (RPA) coupled with CRISPR-Cas12a for the detection of 'Huanong No.1'. The RPA-CRISPR-Cas12a platform was found to have high specificity, with amplification signals only present in 'Huanong No.1'. Additionally, the platform was highly sensitive, with a limit of detection (LOD) of approximately 20 copies. The detection process was fast and could be completed in less than 1 h. This novel platform enables the rapid on-site visualization detection of 'Huanong No.1', eliminating dependence on laboratory conditions and specialized instruments, and can serve as a technical reference for the rapid detection of other GM plants.

Observation-Based Diagnostics of Reactive Nitrogen Recycling through HONO Heterogenous Production: Divergent Implications for Ozone Production and Emission Control.

Understanding of nitrous acid (HONO) production is crucial to photochemical studies, especially in polluted environments like eastern China. In-situ measurements of gaseous and particulate compositions were conducted at a rural coastal site during the 2018 spring Ozone Photochemistry and Export from China Experiment (OPECE). This data set was applied to investigate the recycling of reactive nitrogen through daytime heterogeneous HONO production. Although HONO levels increase during agricultural burning, analysis of the observation data does not indicate more efficient HONO production by agricultural burning aerosols than other anthropogenic aerosols. Box and 1-D modeling analyses reveal the intrinsic relationships between nitrogen dioxide (NO2), particulate nitrate (pNO3), and nitric acid (HNO3), resulting in comparable agreement between observed and simulated HONO concentrations with any one of the three heterogeneous HONO production mechanisms, photosensitized NO2 conversion on aerosols, photolysis of pNO3, and conversion from HNO3. This finding underscores the uncertainties in the mechanistic understanding and quantitative parametrizations of daytime heterogeneous HONO production pathways. Furthermore, the implications for reactive nitrogen recycling, ozone (O3) production, and O3 control strategies vary greatly depending on the HONO production mechanism. On a regional scale, the conversion of HONO from pNO3 can drastically enhance O3 production, while the conversion from NO2 can reduce O3 sensitivity to NOx changes in polluted eastern China.

[Impact of cecal ligation and puncture-induced sepsis on the proliferation and differentiation of intestinal stem cells].

OBJECTIVE: To analyze the impact of cecal ligation and puncture (CLP)-induced sepsis on the proliferation and differentiation of intestinal epithelial cells. METHODS: (1) Animal experiment: sixteen male C57BL/6 mice were divided into sham operation group (Sham group) and CLP-induced sepsis model group (CLP group) by random number table method, with 8 mice in each group. After 5 days of operation, the jejunal tissues were taken for determination of leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) and intestinal alkaline phosphatase (IAP) by polymerase chain reaction (PCR). The translation of LGR5 was detected by Western blotting. The expression of proliferating cell nuclear antigen (Ki67) was analyzed by immunohistochemistry. IAP level was detected by modified calcium cobalt staining and colorimetry. Immunofluorescence staining was used to detect the expression of Paneth cell marker molecule lysozyme 1 (LYZ1) and goblet cell marker molecule mucin 2 (MUC2). (2) Cell experiment: IEC6 cells in logarithmic growth stage were divided into blank control group and lipopolysaccharide (LPS) group (LPS 5 µg/mL). Twenty-four hours after treatment, PCR and Western blotting were used to analyze the transcription and translation of LGR5. The proliferation of IEC6 cells were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining. The transcription and translation of IAP were detected by PCR and colorimetric method respectively. RESULTS: (1) Animal experiment: the immunohistochemical results showed that the positive rate of Ki67 staining in the jejunal tissue of CLP group was lower than that of Sham group [(41.7±2.5)% vs. (48.7±1.4)%, P = 0.01]. PCR and Western blotting results showed that there were no statistical differences in the mRNA and protein expressions of LGR5 in the jejunal tissue between the CLP group and Sham group (Lgr5 mRNA: 0.7±0.1 vs. 1.0±0.2, P = 0.11; LGR5/ß-actin: 0.83±0.17 vs. 0.68±0.19, P = 0.24). The mRNA (0.4±0.1 vs. 1.0±0.1, P < 0.01) and protein (U/g: 47.3±6.0 vs. 73.1±15.3, P < 0.01) levels of IAP in the jejunal tissue were lower in CLP group. Immunofluorescence saining analysis showed that the expressions of LYZ1 and MUC2 in the CLP group were lower than those in the Sham group. (2) Cell experiment: PCR and Western blotting results showed that there was no significant difference in the expression of LGR5 between the LPS group and the blank control group (Lgr5 mRNA: 0.9±0.1 vs. 1.0±0.2, P = 0.33; LGR5/ß-actin: 0.71±0.18 vs. 0.69±0.04, P = 0.81). The proliferation rate of IEC6 cells in the LPS group was lower than that in the blank control group, but there was no significant difference [positivity rate of EdU: (40.5±3.8)% vs. (46.5±3.6)%, P = 0.11]. The mRNA (0.5±0.1 vs. 1.0±0.2, P < 0.01) and protein (U/g: 15.0±4.0 vs. 41.2±10.4, P < 0.01) of IAP in the LPS group were lower than those in the blank control group. CONCLUSIONS: CLP-induced sepsis inhibits the proliferation and differentiation of intestinal epithelial cells, impairing the self-renewal ability of intestinal epithelium.

A Study on the Effect of Executive Control Network Functional Connection on the Therapeutic Efficacy of Repetitive Transcranial Magnetic Stimulation in Alzheimer's Disease.

Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by brain network dysfunction. Few studies have investigated whether the functional connections between executive control networks (ECN) and other brain regions can predict the therapeutic effect of repetitive transcranial magnetic stimulation (rTMS). Objective: The purpose of this study is to examine the relationship between the functional connectivity (FC) within ECN networks and the efficacy of rTMS. Methods: We recruited AD patients for rTMS treatment. We established an ECN using baseline period fMRI data and conducted an analysis of the ECN's FC throughout the brain. Concurrently, the support vector regression (SVR) method was employed to project post-rTMS cognitive scores, utilizing the connectional attributes of the ECN as predictive markers. Results: The average age of the patients was 66.86±8.44 years, with 8 males and 13 females. Significant improvement on most cognitive measures. We use ECN connectivity and brain region functions in baseline patients as features for SVR model training and fitting. The SVR model could demonstrate significant predictability for changes in Montreal Cognitive Assessment scores among AD patients after rTMS treatment. The brain regions that contributed most to the prediction of the model (the top 10% of weights) were located in the medial temporal lobe, middle temporal gyrus, frontal lobe, parietal lobe and occipital lobe. Conclusions: The stronger the antagonism between ECN and parieto-occipital lobe function, the better the prediction of cognitive improvement; the stronger the synergy between ECN and fronto-temporal lobe function, the better the prediction of cognitive improvement.

Ganoderic acid A ameliorates depressive-like behaviors in CSDS mice: Insights from proteomic profiling and molecular mechanisms.

OBJECTIVE: Ganoderic Acid A (GAA), a primary bioactive component in Ganoderma, has demonstrated ameliorative effects on depressive-like behaviors in a Chronic Social Defeat Stress (CSDS) mouse model. This study aims to elucidate the underlying molecular mechanisms through proteomic analysis. METHODS: C57BL/6 J mice were allocated into control (CON), chronic social defeat stress (CSDS), GAA, and imipramine (IMI) groups. Post-depression induction via CSDS, the GAA and IMI groups received respective treatments of GAA (2.5 mg/kg) and imipramine (10 mg/kg) for five days. Behavioral assessments utilized standardized tests. Proteins from the prefrontal cortex were analyzed using LC-MS, with further examination via bioinformatics and PRM for differential expression. Western blot analysis confirmed protein expression levels. RESULTS: Chronic social defeat stress (CSDS) induced depressive-like behaviors in mice, which were significantly alleviated by GAA treatment, comparably to imipramine (IMI). Proteomic analysis identified distinct proteins in control (305), GAA-treated (949), and IMI-treated (289) groups. Enrichment in mitochondrial and synaptic proteins was evident from GO and PPI analyses. PRM analysis revealed significant expression changes in proteins crucial for mitochondrial and synaptic functions (namely, Naa30, Bnip1, Tubgcp4, Atxn3, Carmil1, Nup37, Apoh, Mrpl42, Tprkb, Acbd5, Dcx, Erbb4, Ppp1r2, Fam3c, Rnf112, and Cep41). Western blot validation in the prefrontal cortex showed increased levels of Mrpl42, Dcx, Fam3c, Ppp1r2, Rnf112, and Naa30 following GAA treatment. CONCLUSION: GAA exhibits potential antidepressant properties, with its action potentially tied to the modulation of synaptic functions and mitochondrial activities.

Coexistence of kaposiform hemangioendothelioma and capillary malformation: More than a coincidence? Two case reports.

The coexistence of kaposiform hemangioendothelioma (KHE) and capillary malformation (CM) is quite rare, and few relevant studies can be found to confirm whether this phenomenon is accidental. We diagnosed and treated two such patients, revealing interesting phenomena associated with the development of vascular diseases. These cases offer the possibility that the coexistence of KHE and CM is not accidental and open up a new field of research related to pediatric vascular tumors and vascular malformations. Personalization and precision are required in the diagnosis and treatment of such patients, and the present findings provide a reliable theoretical and practical basis for further research on the pathogenesis and therapy of patients with multiple vascular diseases.

Evidence of Ferromagnetism and Ultrafast Dynamics of Demagnetization in an Epitaxial FeCl2 Monolayer.

The development of two-dimensional (2D) magnetism is driven not only by the interest of low-dimensional physics but also by potential applications in high-density miniaturized spintronic devices. However, 2D materials possessing a ferromagnetic order with a relatively high Curie temperature (Tc) are rare. In this paper, the evidence of ferromagnetism in monolayer FeCl2 on Au(111) surfaces, as well as the interlayer antiferromagnetic coupling of bilayer FeCl2, is characterized by using spin-polarized scanning tunneling microscopy. A Curie temperature (Tc) of ∼147 K is revealed for monolayer FeCl2, based on our static magneto-optical Kerr effect measurements. Furthermore, temperature-dependent magnetization dynamics is investigated by the time-resolved magneto-optical Kerr effect. A transition from one- to two-step demagnetization occurs as the lattice temperature approaches Tc, which supports the Elliott-Yafet spin relaxation mechanism. The findings contribute to a deeper understanding of the underlying mechanisms governing ultrafast magnetization in 2D ferromagnetic materials.

PCR Independent Strategy-Based Biosensors for RNA Detection.

RNA is an important information and functional molecule. It can respond to the regulation of life processes and is also a key molecule in gene expression and regulation. Therefore, RNA detection technology has been widely used in many fields, especially in disease diagnosis, medical research, genetic engineering and other fields. However, the current RT-qPCR for RNA detection is complex, costly and requires the support of professional technicians, resulting in it not having great potential for rapid application in the field. PCR-free techniques are the most attractive alternative. They are a low-cost, simple operation method and do not require the support of large instruments, providing a new concept for the development of new RNA detection methods. This article reviews current PCR-free methods, overviews reported RNA biosensors based on electrochemistry, SPR, microfluidics, nanomaterials and CRISPR, and discusses their challenges and future research prospects in RNA detection.

Implications of PM2.5 chemical composition in modulating microbial community dynamics during spring in Seoul.

Particulate matter with an aerodynamic diameter of 2.5 µm or less (PM2.5) harbors a diverse microbial community. To assess the ecological dynamics and potential health risks associated with airborne microorganisms, it is crucial to understand the factors influencing microbial communities within PM2.5. This study investigated the influence of abiotic parameters, including air pollutants, PM2.5 chemical composition (water-soluble ions and organics), and meteorological variables, on microbial communities in PM2.5 samples collected in Seoul during the spring season. Results revealed a significant correlation between air pollutants and water-soluble ions of PM2.5 with microbial α-diversity indices. Additionally, air pollutants exerted a dominant effect on the microbial community structure, with stronger correlations observed for fungi than bacteria, whereas meteorological variables including temperature, pressure, wind speed, and humidity exerted a limited influence on fungal α-diversity. Furthermore, the results revealed specific water-soluble ions, such as SO42-, NO3-, and NH4+, as important factors influencing fungal α-diversity, whereas K+ negatively correlated with both microbial α-diversity. Moreover, PM2.5 microbial diversity was affected by organic compounds within PM2.5, with fatty acids exhibited a positive correlation with fungal diversity, while dicarboxylic acids exhibited a negative correlation with it. Furthermore, network analysis revealed direct links between air pollutants and dominant bacterial and fungal genera. The air pollutants exhibited a strong correlation with bacterial genera, such as Arthrospira and Clostridium, and fungal genera, including Aureobasidium and Cladosporium. These results will contribute to our understanding of the ecological dynamics of airborne microorganisms and provide insights into the potential risks associated with PM2.5 exposure.

Association between body mass index and delirium incidence in critically ill patients: a retrospective cohort study based on the MIMIC-IV Database.

OBJECTIVES: Delirium is a form of brain dysfunction with high incidence and is associated with many negative outcomes in the intensive care unit. However, few studies have been large enough to reliably examine the associations between body mass index (BMI) and delirium, especially in critically ill patients. The objective of this study was to investigate the association between BMI and delirium incidence in critically ill patients. DESIGN: A retrospective cohort study. SETTING: Data were collected from the Medical Information Mart for Intensive Care-IV V2.0 Database consisting of critically ill participants between 2008 and 2019 at the Beth Israel Deaconess Medical Center in Boston. PARTICIPANTS: A total of 20 193 patients with BMI and delirium records were enrolled in this study and were divided into six groups. PRIMARY OUTCOME MEASURE: Delirium incidence. RESULTS: Generalised linear models and restricted cubic spline analysis were used to estimate the associations between BMI and delirium incidence. A total of 30.81% of the patients (6222 of 20 193) developed delirium in the total cohort. Compared with those in the healthy weight group, the patients in the different groups (underweight, overweight, obesity grade 1, obesity grade 2, obesity grade 3) had different relative risks (RRs): RR=1.10, 95% CI=1.02 to 1.19, p=0.011; RR=0.93, 95% CI=0.88 to 0.97, p=0.003; RR=0.88, 95% CI=0.83 to 0.94, p<0.001; RR=0.94, 95% CI=0.86 to 1.03, p=0.193; RR=1.14, 95% CI=1.03 to 1.25, p=0.010, respectively. For patients with or without adjustment variables, there was an obvious U-shaped relationship between BMI as a continuous variable and delirium incidence. CONCLUSION: BMI was associated with the incidence of delirium. Our results suggested that a BMI higher or lower than obesity grade 1 rather than the healthy weight in critically ill patients increases the risk of delirium incidence.

Exploring the causal relationship between antihypertensive drugs and glioblastoma by combining drug target Mendelian randomization study, eQTL colocalization, and single-cell RNA sequencing.

Recent reports indicate a potential oncogenic role of antihypertensive drugs in common cancers. However, it remains uncertain whether this phenomenon influences the risk of glioblastoma multiforme (GBM). This study aimed to assess the potential causal effects of blood pressure (BP) and antihypertensive drugs on GBM. Genome-wide association study (GWAS) summary statistics for systolic blood pressure (SBP), diastolic blood pressure (DBP), and GBM in Europeans were downloaded. To represent the effects of antihypertensive drugs, we utilized single nucleotide polymorphisms (SNPs) associated with SBP/DBP adjacent to the coding regions of different antihypertensive drugs as instrumental variables to model five antihypertensive drugs, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, ß-receptor blockers (BBs), and thiazide diuretics. Positive control studies were performed using GWAS data in chronic heart failure. The primary method for causality estimation was the inverse-variance-weighted method. Mendelian randomization analysis showed that BBs with the ß1-adrenergic receptor (ADRB1) as a therapeutic target could significantly reduce the risk of GBM by mediating DBP (OR = 0.431, 95% CI: 0.267-0.697, p < .001) and that they could also significantly reduce the risk of GBM by mediating SBP (OR = 0.595, 95% CI: 0.422-0.837, p = .003). Sensitivity analysis and colocalization analysis reinforced the robustness of these findings. Finally, the low expression of the ADRB1 gene in malignant gliomas was found by GBM data from TCGA and single-cell RNA sequencing, which most likely contributed to the poor prognosis of GBM patients. In summary, our study provides preliminary evidence of some causal relationship between ADRB1-targeted BBs and glioblastoma development. However, more studies are needed to validate these findings and further reveal the complex relationship between BP and GBM.

Improvement of the anthropogenic emission rate estimate in Ulaanbaatar, Mongolia, for 2020-21 winter.

Ulaanbaatar (UB), the fast-growing capital of Mongolia, is known for its world's worst level of particulate matter (PM) concentrations in winter. However, current anthropogenic emission inventories over the UB are based on data from more than fifteen years ago, and satellite observations are scarce because UB is in high latitudes. During the winter of 2020-21, the first period of the Fine Particle Research Initiative in East Asia considering the National Differences (FRIEND), several times higher concentrations of PM in UB compared to other urban sites in East Asia were observed but not reproduced with a chemical transport model mainly due to the underestimated anthropogenic emissions. Therefore, we devised a method for sequentially adjusting emissions based on the reactivity of PM precursors using ground observations. We scaled emission rates for the inert species (CO, elemental carbon (EC), and organic carbon (OC)) to reproduce their observed ambient concentrations, followed by SO2 to reproduce the concentration of SO42-, which was examined to have the least uncertainty based on the abundance of observed NH3, and finally NO and NH3 for NO3-, and NH4+. This improved estimation is compared to regional inventories for Asia and suggests more than an order of magnitude increase in anthropogenic emissions in UB. Using the improved emission inventory, we were able to successfully reproduce independent observation data on PM2.5 concentrations in UB in December 2021 from the U.S. Embassy. During the campaign period, we found more than 50% of the SO42-, NO3-, and NH4+ increased in UB due to the improvement could travel to Beijing, China (BJ), and about 20% of the SO42- could travel to Noto, Japan (NT), more than 3000 km away. Also, the anthropogenic emissions in UB can effectively increase OC, NO3-, and NH4+ concentrations in BJ when Gobi dust storms occur.

Effects of volatile organic compounds and new particle formation on real-time hygroscopicity of PM2.5 particles in Seosan, Republic of Korea.

The hygroscopicity of PM2.5 particles plays an important role in PM2.5 haze in Northeast Asian countries by influencing particle growth and chemical composition. New particle formation (NPF) and atmospheric volatile organic compounds (VOCs) are factors that influence particle hygroscopicity. However, the lack of real-time hygroscopicity measurements has deterred the understanding of their effects on particle hygroscopicity. In this study, two intensive monitoring campaigns were conducted during the summer of 2021 and spring of 2022 using real-time aerosol instruments, including a humidified tandem differential mobility analyzer (HTDMA), in Seosan, Republic of Korea. The hygroscopicity parameter κ was calculated from the real-time HTDMA measurement data (κGf). The diurnal variations in κGf exhibited strong inverse linear correlations with the total concentration of VOCs (CTVOC) during the two campaigns. The higher atmospheric CTVOC in summer increased the growth rate of the particle diameter from 10 to 40 nm (6 nm/h) compared with that in spring (2.7 nm/h), resulting in a faster change in κGf for 40-nm particles in summer than in spring because of the increase in organic matter in the chemical compositions of particles. In addition, NPF events introduced additional tiny fresh particles into the atmosphere, which reduced the κGf of 40-nm particles and increased the intensity of the less hygroscopic peaks (κGf < 0.1) of κ-probability density functions (κ-PDF) in NPF days. However, 100-nm particles exhibited fewer changes in κGf than 40-nm particles, resulting in additional dominant hygroscopic peaks (κ âˆ¼ 0.2) of κ-PDFs in both NPF and non-NPF days. When κGf values measured in Seosan were compared with those in other Northeast Asian countries in the literature, the κ values for 40-nm particles were lower than those (κ > 0.2) measured in Beijing and Guangzhou, but those for 100-nm particles were close to those measured in the two cities.