Spatiotemporal transcriptome atlas reveals the regional specification of the developing human brain.

Different functional regions of brain are fundamental for basic neurophysiological activities. However, the regional specification remains largely unexplored during human brain development. Here, by combining spatial transcriptomics (scStereo-seq) and scRNA-seq, we built a spatiotemporal developmental atlas of multiple human brain regions from 6-23 gestational weeks (GWs). We discovered that, around GW8, radial glia (RG) cells have displayed regional heterogeneity and specific spatial distribution. Interestingly, we found that the regional heterogeneity of RG subtypes contributed to the subsequent neuronal specification. Specifically, two diencephalon-specific subtypes gave rise to glutamatergic and GABAergic neurons, whereas subtypes in ventral midbrain were associated with the dopaminergic neurons. Similar GABAergic neuronal subtypes were shared between neocortex and diencephalon. Additionally, we revealed that cell-cell interactions between oligodendrocyte precursor cells and GABAergic neurons influenced and promoted neuronal development coupled with regional specification. Altogether, this study provides comprehensive insights into the regional specification in the developing human brain.

Integrating single-cell datasets with ambiguous batch information by incorporating molecular network features.

With the rapid development of single-cell sequencing techniques, several large-scale cell atlas projects have been launched across the world. However, it is still challenging to integrate single-cell RNA-seq (scRNA-seq) datasets with diverse tissue sources, developmental stages and/or few overlaps, due to the ambiguity in determining the batch information, which is particularly important for current batch-effect correction methods. Here, we present SCORE, a simple network-based integration methodology, which incorporates curated molecular network features to infer cellular states and generate a unified workflow for integrating scRNA-seq datasets. Validating on real single-cell datasets, we showed that regardless of batch information, SCORE outperforms existing methods in accuracy, robustness, scalability and data integration.

A single-cell RNA-seq survey of the developmental landscape of the human prefrontal cortex.

The mammalian prefrontal cortex comprises a set of highly specialized brain areas containing billions of cells and serves as the centre of the highest-order cognitive functions, such as memory, cognitive ability, decision-making and social behaviour. Although neural circuits are formed in the late stages of human embryonic development and even after birth, diverse classes of functional cells are generated and migrate to the appropriate locations earlier in development. Dysfunction of the prefrontal cortex contributes to cognitive deficits and the majority of neurodevelopmental disorders; there is therefore a need for detailed knowledge of the development of the prefrontal cortex. However, it is still difficult to identify cell types in the developing human prefrontal cortex and to distinguish their developmental features. Here we analyse more than 2,300 single cells in the developing human prefrontal cortex from gestational weeks 8 to 26 using RNA sequencing. We identify 35 subtypes of cells in six main classes and trace the developmental trajectories of these cells. Detailed analysis of neural progenitor cells highlights new marker genes and unique developmental features of intermediate progenitor cells. We also map the timeline of neurogenesis of excitatory neurons in the prefrontal cortex and detect the presence of interneuron progenitors in early developing prefrontal cortex. Moreover, we reveal the intrinsic development-dependent signals that regulate neuron generation and circuit formation using single-cell transcriptomic data analysis. Our screening and characterization approach provides a blueprint for understanding the development of the human prefrontal cortex in the early and mid-gestational stages in order to systematically dissect the cellular basis and molecular regulation of prefrontal cortex function in humans.

Changes in cognitive function, synaptic structure and protein expression after long-term exposure to 2.856 and 9.375 GHz microwaves.

Health hazards from long-term exposure to microwaves, especially the potential for changes in cognitive function, are attracting increasing attention. The purpose of this study was to explore changes in spatial learning and memory and synaptic structure and to identify differentially expressed proteins in hippocampal and serum exosomes after long-term exposure to 2.856 and 9.375 GHz microwaves. The spatial reference learning and memory abilities and the structure of the DG area were impaired after long-term exposure to 2.856 and 9.375 GHz microwaves. We also found a decrease in SNARE-associated protein Snapin and an increase in charged multivesicular body protein 3 in the hippocampus, indicating that synaptic vesicle recycling was inhibited and consistent with the large increase in presynaptic vesicles. Moreover, we investigated changes in serum exosomes after 2.856 and 9.375 GHz microwave exposure. The results showed that long-term 2.856 GHz microwave exposure could induce a decrease in calcineurin subunit B type 1 and cytochrome b-245 heavy chain in serum exosomes. While the 9.375 GHz long-term microwave exposure induced a decrease in proteins (synaptophysin-like 1, ankyrin repeat and rabankyrin-5, protein phosphatase 3 catalytic subunit alpha and sodium-dependent phosphate transporter 1) in serum exosomes. In summary, long-term microwave exposure could lead to different degrees of spatial learning and memory impairment, EEG disturbance, structural damage to the hippocampus, and differential expression of hippocampal tissue and serum exosomes.

Hollow Starlike Ag/CoMo-LDH Heterojunction with a Tunable d-Band Center for Boosting Oxygen Evolution Reaction Electrocatalysis.

It is a challenging task to utilize efficient electrocatalytic metal hydroxide-based materials for the oxygen evolution reaction (OER) in order to produce clean hydrogen energy through water splitting, primarily due to the restricted availability of active sites and the undesirably high adsorption energies of oxygenated species. To address these challenges simultaneously, we intentionally engineer a hollow star-shaped Ag/CoMo-LDH heterostructure as a highly efficient electrocatalytic system. This design incorporates a considerable number of heterointerfaces between evenly dispersed Ag nanoparticles and CoMo-LDH nanosheets. The heterojunction materials have been prepared using self-assembly, in situ transformation, and spontaneous redox processes. The nanosheet-integrated hollow architecture can prevent active entities from agglomeration and facilitate mass transportation, enabling the constant exposure of active sites. Specifically, the powerful electronic interaction within the heterojunction can successfully regulate the Co3+/Co2+ ratio and the d-band center, resulting in rational optimization of the adsorption and desorption of the intermediates on the site. Benefiting from its well-defined multifunctional structures, the Ag0.4/CoMo-LDH with optimal Ag loading exhibits impressive OER activity, the overpotential being 290 mV to reach a 10 mA cm-2 current density. The present study sheds some new insights into the electron structure modulation of hollow heterostructures toward rationally designing electrocatalytic materials for the OER.

Physiological and Psychological Stress of Microwave Radiation-Induced Cardiac Injury in Rats.

Electromagnetic waves are widely used in both military and civilian fields, which could cause long-term and high-power exposure to certain populations and may pose a health hazard. The aim of this study was to simulate the long-term and high-power working environment of workers using special electromagnetic radiation occupations to clarify the radiation-induced stress response and cardiac damage and thus gain insights into the mechanisms of injuries caused by electromagnetic radiation. In this study, the combination of microwave and stress was an innovative point, aiming to broaden the research direction with regard to the effect and mechanism of cardiac injury caused by radiation. The myocardial structure was observed by optical and transmission electron microscope, mitochondrial function was detected by flow cytometry, oxidative-stress markers were detected by microplate reader, serum stress hormone was detected by radioimmunoassay, and heart rate variability (HRV) was analyzed by multichannel-physiological recorder. The rats were weighed and subjected to an open field experiment. Western blot (WB) and immunofluorescence (IF) were used to detect the expressions and distributions of JNK (c-Jun N-terminal kinase), p-JNK (phosphorylated c-Jun N-terminal kinase), HSF1 (heat shock factor), and NFATc4 (nuclear factor of activated T-cell 4). This study found that radiation could lead to the disorganization, fragmentation, and dissolution of myocardial fibers, severe mitochondrial cavitation, mitochondrial dysfunction, oxidative-stress injury in myocardium, increase to stress hormone in serum, significant changes in HRV, and a slow gain in weight. The open field experiment indicated that the rats experienced anxiety and depression and had decreased exercise capacity after radiation. The expressions of JNK, p-JNK, HSF1, and NFATc4 in myocardial tissue were all increased. The above results suggested that 30 mW/cm2 of S-band microwave radiation for 35 min could cause both physiological and psychological stress damage in rats; the damage was related to the activation of the JNK pathway, which provided new ideas for research on protection from radiation.

Role of Cx43 in iPSC-CM Damage Induced by Microwave Radiation.

The heart is one of the major organs affected by microwave radiation, and these effects have been extensively studied. Previous studies have shown that microwave-radiation-induced heart injury might be related to the abnormal expression and distribution of Cx43. In order to make the research model closer to humans, we used iPSC-CMs as the cell injury model to investigate the biological effect and mechanism of iPSC-CM injury after microwave radiation. To model the damage, iPSC-CMs were separated into four groups and exposed to single or composite S-band (2.856 GHz) and X-band (9.375 GHz) microwave radiation sources with an average power density of 30 mW/cm2. After that, FCM was used to detect cell activity, and ELISA was used to detect the contents of myocardial enzymes and injury markers in the culture medium, and it was discovered that cell activity decreased and the contents increased after radiation. TEM and SEM showed that the ultrastructure of the cell membrane, mitochondria, and ID was damaged. Mitochondrial function was aberrant, and glycolytic capacity decreased after exposure. The electrical conduction function of iPSC-CM was abnormal; the conduction velocity was decreased, and the pulsation amplitude was reduced. Wb, qRT-PCR, and IF detections showed that the expression of Cx43 was decreased and the distribution of Cx43 at the gap junction was disordered. Single or composite exposure to S- and X-band microwave radiation caused damage to the structure and function of iPSC-CMs, primarily affecting the cell membrane, mitochondria, and ID. The composite exposure group was more severely harmed than the single exposure group. These abnormalities in structure and function were related to the decreased expression and disordered distribution of Cx43.

Metformin Ameliorates 2.856 GHz Microwave- Radiation-Induced Reproductive Impairments in Male Rats via Inhibition of Oxidative Stress and Apoptosis.

The reproductive system has been increasingly implicated as a sensitive target of microwave radiation. Oxidative stress plays a critical role in microwave radiation -induced reproductive damage, though precise mechanisms are obscure. Metformin, a widely used antidiabetic drug, has emerged as an efficient antioxidant against a variety of oxidative injuries. In the present study, we hypothesized that metformin can function as an antioxidant and protect the reproductive system from microwave radiation. To test this hypothesis, rats were exposed to 2.856 GHz microwave radiation for 6 weeks to simulate real-life exposure to high-frequency microwave radiation. Our results showed that exposure to 2.856 GHz microwave radiation elicited serum hormone disorder, decreased sperm motility, and depleted sperm energy, and it induced abnormalities of testicular structure as well as mitochondrial impairment. Metformin was found to effectively protect the reproductive system against structural and functional impairments caused by microwave radiation. In particular, metformin can ameliorate microwave-radiation-induced oxidative injury and mitigate apoptosis in the testis, as determined by glutathione/-oxidized glutathione (GSH/GSSG), lipid peroxidation, and protein expression of heme oxygenase-1 (HO-1). These findings demonstrated that exposure to 2.856 GHz microwave radiation induces obvious structural and functional impairments of the male reproductive system, and suggested that metformin can function as a promising antioxidant to inhibit microwave-radiation-induced harmful effects by inhibiting oxidative stress and apoptosis.

[Effect of Diurnal Temperature Range on the Number of Residents Hospitalized Due to Stroke in Lanzhou].

Objective To analyze the relationship between diurnal temperature range (DTR) and the hospitalization of stroke in Lanzhou,so as to provide a scientific basis for probing into the mechanism of temperature changes in inducing stroke and formulating comprehensive prevention and control measures for stroke by relevant departments.Methods The information of the patients hospitalized due to stroke in Lanzhou during January 2014 to December 2019 and the air pollutants (PM10,SO2,and NO2) and meteorological data in the same period were collected for statistical analysis.Spearman rank correlation analysis was performed to analyze the correlations between air pollutants and meteorological factors.The distributed lag nonlinear model was adopted to fit the relationship between DTR and the number of stroke inpatients,and three-dimensional diagrams and the correlation diagrams of DTR against stroke risk were established.The stratified analysis was performed according to gender and age (< 65 years and ≥65 years).Results From 2014 to 2019,a total of 92 812 stroke patients were hospitalized in Lanzhou,with a male-to-female ratio of 1.35:1.There was a nonlinear relationship between DTR and the number of stroke inpatients in Lanzhou,which presented a lag effect.The low DTR at 4.5 ℃ had the largest RR value of 1.25 (95%CI=1.16-1.35) for stroke inpatients at a cumulative lag of 18 d.The effect of high DTR (18.5 ℃) on the hospitalization of stroke patients peaked at a cumulative lag of 21 d,with an RR value of 1.09 (95%CI=1.01-1.18).The stratified analysis results suggested that low levels of DTR had greater effects on the hospitalization of male stroke patients and stroke patients <65 years.Conclusions Short-term exposure to different levels of DTR had an impact on the number of stroke inpatients,and low levels of DTR had a slightly greater impact on stroke inpatients than high levels of DTR.Importance should be attached to the protection of males and people aged <65 years at low levels of DTR.

[Quality evaluation and multi-spectral identification of origin herbs of Lonicerae Japonicae Flos based on grey correlation-TOPSIS method].

The grey correlation-TOPSIS method was used to evaluate the quality of the origin herbs of Lonicerae Japonicae Flos, and the Fourier transform near-infrared(NIR) and mid-infrared(MIR) spectroscopy was applied to establish the identification model of origin herbs of Lonicerae Japonicae Flos by combining chemometrics and spectral fusion strategies. The content of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, caffeic acid, secoxyloganin, isoquercitrin, isochlorogenic acid B, isochlorogenic acid A, and isochlorogenic acid C in six origin herbs of Lonicerae Japonicae Flos was determined by high-performance liquid chromatography(HPLC), and their quality was evaluated by the grey correlation-TOPSIS method. The Fourier transform NIR and MIR spectra of six origin herbs of Lonicerae Japonicae Flos(Lonicera japonica, L. macranthoides, L. hypoglauca, L. fulvotomentosa, L. confuse, and L. similis) were collected. At the same time, principal component analysis(PCA), support vector machine(SVM), and spectral data fusion technology were combined to determine the optimal identification method for the origin herbs of Lonicerae Japonicae Flos. There were differences in the quality of the origin herbs of Lonicerae Japonicae Flos. Specifically, there were significant differences between L. japonica and the other five origin herbs(P<0.01). The quality of L. similis was significantly different from that of L. fulvotomentosa, L. macranthoides, and L. hypoglauca(P=0.008, 0.027, 0.01), and there were also significant differences in the quality of L. hypoglauca and L. confuse(P=0.001). The PCA and SVM 2D models based on a single spectrum could not be used for the effective identification of the origin herbs of Lonicerae Japonicae Flos. The data fusion combined with the SVM model further improved the identification accuracy, and the identification accuracy of the mid-level data fusion reached 100%. Therefore, the grey correlation-TOPSIS method can be used to evaluate the quality of the origin herbs of Lonicerae Japonicae Flos. Based on the infrared spectral data fusion strategy and SVM chemometric model, it can accurately identify the origin herbs of Lonicerae Japonicae Flos, which can provide a new method for the origin identification of medicinal materials of Lonicerae Japonicae Flos.

Isobaric Stable Isotope N-Phosphorylation Labeling (iSIPL) for Ultrasensitive Proteome Quantification.

Stable isotope chemical labeling methods have been widely used for high-throughput mass spectrometry (MS)-based quantitative proteomics in biological and clinical applications. However, the existing methods are far from meeting the requirements for high sensitivity detection. In the present study, a novel isobaric stable isotope N-phosphorylation labeling (iSIPL) strategy was developed for quantitative proteome analysis. The tryptic peptides were selectively labeled with iSIPL tag to generate the novel reporter ions containing phosphoramidate P-N bond with high intensities under lower collision energies. iSIPL strategy are suitable for peptide sequencing and quantitative analysis with high sensitivity and accuracy even for samples of limited quantity. Furthermore, iSIPL coupled with affinity purification and mass spectrometry was applied to measure the dynamics of cyclin dependent kinase 9 (CDK9) interactomes during transactivation of the HIV-1 provirus. The interaction of CDK9 with PARP13 was found to significantly decrease during Tat-induced activation of HIV-1 gene transcription, suggesting the effectiveness of iSIPL strategy in dynamic analysis of protein-protein interaction in vivo. More than that, the proposed iSIPL strategy would facilitate large-scale accurate quantitative proteomics by increasing multiplexing capability.

Dissecting the transcriptome landscape of the human fetal neural retina and retinal pigment epithelium by single-cell RNA-seq analysis.

The developmental pathway of the neural retina (NR) and retinal pigment epithelium (RPE) has been revealed by extensive research in mice. However, the molecular mechanisms underlying the development of the human NR and RPE, as well as the interactions between these two tissues, have not been well defined. Here, we analyzed 2,421 individual cells from human fetal NR and RPE using single-cell RNA sequencing (RNA-seq) technique and revealed the tightly regulated spatiotemporal gene expression network of human retinal cells. We identified major cell classes of human fetal retina and potential crucial transcription factors for each cell class. We dissected the dynamic expression patterns of visual cycle- and ligand-receptor interaction-related genes in the RPE and NR. Moreover, we provided a map of disease-related genes for human fetal retinal cells and highlighted the importance of retinal progenitor cells as potential targets of inherited retinal diseases. Our findings captured the key in vivo features of the development of the human NR and RPE and offered insightful clues for further functional studies.

Development of Physiology Based Pharmacokinetic Model to Predict the Drug Interactions of Voriconazole and Venetoclax.

PURPOSE: Venetoclax (VEN), an anti-tumor drug that is a substrate of cytochrome P450 3A enzyme (CYP3A4), is used to treat leukemia. Voriconazole (VCZ) is an antifungal medication that inhibits CYP3A4. The goal of this study is to predict the effect of VCZ on VEN exposure. METHOD: Two physiological based pharmacokinetics (PBPK) models were developed for VCZ and VEN using the bottom-up and top-down method. VCZ model was also developed to describe the effect of CYP2C19 polymorphism on its pharmacokinetics (PK). The reversible inhibition constant (Ki) of VCZ for CYP3A4 was calibrated using drug-drug interaction (DDI) data of midazolam and VCZ. The clinical verified VCZ and VEN model were used to predict the DDI of VCZ and VEN at clinical dosing scenario. RESULT: VCZ model predicted VCZ exposure in the subjects of different CYP2C19 genotype and DDI related fold changes of sensitive CYP3A substrate with acceptable prediction error. VEN model can capture PK of VEN with acceptable prediction error. The DDI PBPK model predicted that VCZ increased the exposure of VEN by 4.5-9.6 fold. The increase in VEN exposure by VCZ was influenced by subject's CYP2C19 genotype. According to the therapeutic window, VEN dose should be reduced to 100 mg when co-administered with VCZ. CONCLUSION: The PBPK model developed here could support individual dose adjustment of VEN and DDI risk assessment. Predictions using the robust PBPK model confirmed that the 100 mg dose adjustment is still applicable in the presence of VCZ with high inter-individual viability.

Changes in rat spatial learning and memory as well as serum exosome proteins after simultaneous exposure to 1.5 GHz and 4.3 GHz microwaves.

This study aimed to elucidate the effects and biological targets sensitive to simultaneous 1.5 and 4.3 GHz microwave exposure in rats. A total of 120 male Wistar rats were divided randomly into four groups: the sham (S group), 1.5 GHz microwave exposure (L group), 4.3 GHz microwave exposure (C group) and simultaneous 1.5 and 4.3 GHz microwave exposure (LC group) groups. Spatial learning and memory, cortical electrical activity, and hippocampal ultrastructure were assessed by the Morris Water Maze, electroencephalography, and transmission electron microscopy, respectively. Additionally, serum exosomes were isolated by ultracentrifugation and assessed by Western blotting, nanoparticle tracking and transmission electron microscopy. The serum exosome protein content was assessed by label-free quantitative proteomics. Impaired spatial learning and memory decreased cortical excitability, and damage to the hippocampal ultrastructure were observed in groups exposed to microwaves, especially the L and LC groups. A total of 54, 145 and 296 exosomal proteins were differentially expressed between the S group and the L, C and LC groups, respectively. These differentially expressed proteins were involved in the synaptic vesicle cycle and SNARE interactions during vesicular transport. Additionally, VAMP8, Syn7 and VMAT are potential serum markers of simultaneous microwave exposure. Thus, exposure to 1.5 and 4.3 GHz microwaves induced impairments in spatial learning and memory, and simultaneous microwave exposure had the most severe effects.

Immune Responses to Multi-Frequencies of 1.5 GHz and 4.3 GHz Microwave Exposure in Rats: Transcriptomic and Proteomic Analysis.

With the rapidly increasing application of microwave technologies, the anxiety and speculation about microwave induced potential health hazards has been attracting more and more attention. In our daily life, people are exposed to complex environments with multi-frequency microwaves, especially L band and C band microwaves, which are commonly used in communications. In this study, we exposed rats to 1.5 GHz (L10), 4.3 GHz (C10) or multi-frequency (LC10) microwaves at an average power density of 10 mW/cm2. Both single and multi-frequency microwaves induced slight pathological changes in the thymus and spleen. Additionally, the white blood cells (WBCs) and lymphocytes in peripheral blood were decreased at 6 h and 7 d after exposure, suggesting immune suppressive responses were induced. Among lymphocytes, the B lymphocytes were increased while the T lymphocytes were decreased at 7 d after exposure in the C10 and LC10 groups, but not in the L10 group. Moreover, multi-frequency microwaves regulated the B and T lymphocytes more strongly than the C band microwave. The results of transcriptomics and proteomics showed that both single and multi-frequency microwaves regulated numerous genes associated with immune regulation and cellular metabolism in peripheral blood and in the spleen. However, multi-frequency microwaves altered the expression of many more genes and proteins. Moreover, multi-frequency microwaves down-regulated T lymphocytes' development, differentiation and activation-associated genes, while they up-regulated B lymphocytes' activation-related genes. In conclusion, multi-frequency microwaves of 1.5 GHz and 4.3 GHz produced immune suppressive responses via regulating immune regulation and cellular metabolism-associated genes. Our findings provide meaningful information for exploring potential mechanisms underlying multi-frequency induced immune suppression.

Lipid Peroxides Mediated Ferroptosis in Electromagnetic Pulse-Induced Hippocampal Neuronal Damage via Inhibition of GSH/GPX4 Axis.

Electromagnetic pulse (EMP) radiation was reported to be harmful to hippocampal neurons. However, the mechanism underlying EMP-induced neuronal damage remains unclear. In this paper, for the first time, we attempted to investigate the involvement of ferroptosis in EMP-induced neuronal damage and its underlying mechanism. In vivo studies were conducted with a rat model to examine the association of ferroptosis and EMP-induced hippocampal neuronal damage. Moreover, in vitro studies were conducted with HT22 neurons to investigate the underlying mechanism of EMP-induced neuronal ferroptosis. In vivo results showed that EMP could induce learning and memory impairment of rats, ferroptotic morphological damages to mitochondria, accumulation of malonaldehyde (MDA) and iron, overexpression of prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA, and downregulation of GPX4 protein in rat hippocampus. In vitro results showed that EMP could induce neuronal death, MDA accumulation, iron overload, PTGS2 overexpression, and GPX4 downregulation in HT22 neurons. These adverse effects could be reversed by either lipid peroxides scavenger ferrostatin-1 or overexpression of GPX4. These results suggest that EMP radiation can induce ferroptosis in hippocampal neurons via a vicious cycle of lipid peroxides accumulation and GSH/GPX4 axis downregulation. Lipid peroxides and the GSH/GPX4 axis provide potential effective intervention targets to EMP-induced hippocampal neuronal damage.

Discovery of Hyrtinadine A and Its Derivatives as Novel Antiviral and Anti-Phytopathogenic-Fungus Agents.

Plant diseases caused by viruses and fungi have a serious impact on the quality and yield of crops, endangering food security. The use of new, green, and efficient pesticides is an important strategy to increase crop output and deal with the food crisis. Ideally, the best pesticide innovation strategy is to find and use active compounds from natural products. Here, we took the marine natural product hyrtinadine A as the lead compound, and designed, synthesized, and systematically investigated a series of its derivatives for their antiviral and antifungal activities. Compound 8a was found to have excellent antiviral activity against the tobacco mosaic virus (TMV) (inactivation inhibitory effect of 55%/500 µg/mL and 19%/100 µg/mL, curative inhibitory effect of 52%/500 µg/mL and 22%/100 µg/mL, and protection inhibitory effect of 57%/500 µg/mL and 26%/100 µg/mL) and emerged as a novel antiviral candidate. These compound derivatives displayed broad-spectrum fungicidal activities against 14 kinds of phytopathogenic fungi at 50 µg/mL and the antifungal activities of compounds 5c, 5g, 6a, and 6e against Rhizoctonia cerealis are higher than that of the commercial fungicide chlorothalonil. Therefore, this study could lay a foundation for the application of hyrtinadine A derivatives in plant protection.

Interaction between Dexamethasone, Ropivacaine, and Contrast Media Used in Interventional Pain Treatment: Considerations in Safety.

Background and Objectives: Although epidural steroid injections are used as an effective treatment, this technique is associated with rare but serious ischemic complications, especially when particulate steroids are used. However, recent studies have reported that even if non-particulate steroids are used, particulates are formed by the interaction with some local anesthetics (LA), causing ischemic complications. This observational study evaluated commonly used combinations of non-particulate steroids and LA with contrast media via microscopic analysis and analyzed the chemical properties of each mixture to identify the correlation of particulate formation. Materials and Methods: Commonly used clinical non-particulate and particulate steroids, contrast media, and LA agent combinations were evaluated macroscopically and microscopically. The pH values were also measured at both room temperature (26 °C) and body temperature (36 °C). Where particulates were observed, the particulate size was measured. Results: Macroscopically, the mixture of non-particulate steroid and ropivacaine had a slightly cloudy appearance at all concentrations, but there was no visible particulate. However, when observed under a microscope, the pH-dependent particulate formation was observed at all concentration combinations tested. (0.1% ropivacaine: from 19 µm to 70 µm, and 0.2% ropivacaine: from 37 µm to 108 µm at room temperature (26 °C)). When contrast media was mixed or the temperature was raised to body temperature (36 °C), the number and size of the particulates decreased or dissolved. Conclusions: The combination of ropivacaine and dexamethasone, a non-particulate steroid, mainly used in epidural injections, forms particulates. However, when mixed with contrast media, particulates are dissolved because of changes in pH and factors affecting particulate formation. In fluoroscopy-guided injections, the use of contrast media could resolve particulate formation.

[Air Temperature Affects the Hospital Admission for Cardiovascular Diseases among Rural Residents in Dingxi City].

Objective To explore the effect of air temperature on the hospitalization of rural residents with cardiovascular diseases and its lag effect in Dingxi city. Methods The meteorological data and air pollution data of Dingxi city from 2018 to 2019,as well as the daily hospitalization data of rural residents due to cardiovascular diseases,were collected.The distributed lag non-linear models were employed to analyze the relationship between daily mean air temperature and the number of inpatients with cardiovascular diseases.Meanwhile,stratified analysis was carried out according to gender,age,and disease. Results There was a non-linear relationship between air temperature and the number of hospitalized rural residents with cardiovascular diseases in Dingxi city.The exposure-response curve approximated a bell shape.The curves for different cardiovascular diseases appeared similar shapes,with different temperature thresholds.Low temperature(-7 ℃) and moderately low temperature(0 ℃) exhibited a cumulative lag effect on the number of patients hospitalized with cardiovascular diseases.With a cumulative lag of 7 days at -7 ℃ and 14 days at 0 ℃,the RR values peaked,which were 1.121(95% CI=1.002-1.255) and 1.198(95% CI=1.123-1.278),respectively.With a cumulative lag of 14 days at 0 ℃,the RR values were 1.034(95% CI=1.003-1.077) and 1.039(95% CI=1.004-1.066) for the number of hospitalized patients with ischemic heart disease and heart rhythm disorders,respectively.The cumulative lag effects of moderately high temperature(17 ℃) and high temperature(21 ℃) on ischemic heart disease,heart rhythm disorders,and cerebrovascular disease all peaked on that day.Specifically,the RR values at 17 ℃ and 21 ℃ were 1.148(95% CI=1.092-1.206) and 1.176(95% CI=1.096-1.261) for ischemic heart disease,1.071(95% CI=1.001-1.147) and 1.112(95% CI=1.011-1.223) for heart rhythm disorders,and 1.084(95% CI=1.025-1.145) and 1.094(95% CI=1.013-1.182) for cerebrovascular disease,respectively.There was no cumulative lag effect of air temperature on the number of hospitalized patients with heart failure.In addition,stratified analysis showed that low temperature(-7 ℃) and moderately low temperature(0 ℃) affected the number of hospitalized female patients with cardiovascular diseases,and only moderately low temperature(0 ℃) affected males.The cumulative lag effect of high temperature on females was higher than that on males.Air temperature exhibited a stronger impact on female patients than on male patients. Additionally,the population aged<65 years old was more sensitive to low temperature and high temperature than that aged ≥65 years old. Conclusions Air temperature changes increase the hospitalization risk of rural residents with cardiovascular diseases in Dingxi city,which presents a lag effect.The effects of air temperature on patients hospitalized due to cardiovascular diseases varied among different etiologies,genders,and ages.It is necessary to emphasize on the impact of temperature changes on health in residents,especially for key populations such as females,people aged<65 years old,and those with ischemic heart disease.

Low p-SYN1 (Ser-553) Expression Leads to Abnormal Neurotransmitter Release of GABA Induced by Up-Regulated Cdk5 after Microwave Exposure: Insights on Protection and Treatment of Microwave-Induced Cognitive Dysfunction.

With the wide application of microwave technology, concerns about its health impact have arisen. The signal transmission mode of the central nervous system and neurons make it particularly sensitive to electromagnetic exposure. It has been reported that abnormal release of amino acid neurotransmitters is mediated by alteration of p-SYN1 after microwave exposure, which results in cognitive dysfunction. As the phosphorylation of SYN1 is regulated by different kinases, in this study we explored the regulatory mechanisms of SYN1 fluctuations following microwave exposure and its subsequent effect on GABA release, aiming to provide clues on the mechanism of cognitive impairment caused by microwave exposure. In vivo studies with Timm and H&E staining were adopted and the results showed abnormality in synapse formation and neuronal structure, explaining the previously-described deficiency in cognitive ability caused by microwave exposure. The observed alterations in SYN1 level, combined with the results of earlier studies, indicate that SYN1 and its phosphorylation status (ser-553 and ser62/67) may play a role in the abnormal release of neurotransmitters. Thus, the role of Cdk5, the upstream kinase regulating the formation of p-SYN1 (ser-553), as well as that of MEK, the regulator of p-SYN1 (ser-62/67), were investigated both in vivo and in vitro. The results showed that Cdk5 was a negative regulator of p-SYN1 (ser-553) and that its up-regulation caused a decrease in GABA release by reducing p-SYN1 (ser-553). While further exploration still needed to elaborate the role of p-SYN1 (ser-62/67) for neurotransmitter release, MEK inhibition had was no impact on p-Erk or p-SYN1 (ser-62/67) after microwave exposure. In conclusion, the decrease of p-SYN1 (ser-553) may result in abnormalities in vesicular anchoring and GABA release, which is caused by increased Cdk5 regulated through Calpain-p25 pathway after 30 mW/cm2 microwave exposure. This study provided a potential new strategy for the prevention and treatment of microwave-induced cognitive dysfunction.