Phylogenomic analyses and reclassification of the Mesorhizobium complex: proposal for 9 novel genera and reclassification of 15 species.

BACKGROUD: The genus Mesorhizobium is shown by phylogenomics to be paraphyletic and forms part of a complex that includes the genera Aminobacter, Aquamicrobium, Pseudaminobacter and Tianweitania. The relationships for type strains belong to these genera need to be carefully re-evaluated. RESULTS: The relationships of Mesorhizobium complex are evaluated based on phylogenomic analyses and overall genome relatedness indices (OGRIs) of 61 type strains. According to the maximum likelihood phylogenetic tree based on concatenated sequences of 539 core proteins and the tree constructed using the bac120 bacterial marker set from Genome Taxonomy Database, 65 type strains were grouped into 9 clusters. Moreover, 10 subclusters were identified based on the OGRIs including average nucleotide identity (ANI), average amino acid identity (AAI) and core-proteome average amino acid identity (cAAI), with AAI and cAAI showing a clear intra- and inter-(sub)cluster gaps of 77.40-80.91% and 83.98-86.16%, respectively. Combined with the phylogenetic trees and OGRIs, the type strains were reclassified into 15 genera. This list includes five defined genera Mesorhizobium, Aquamicrobium, Pseudaminobacter, Aminobacterand Tianweitania, among which 40/41 Mesorhizobium species and one Aminobacter species are canonical legume microsymbionts. The other nine (sub)clusters are classified as novel genera. Cluster III, comprising symbiotic M. alhagi and M. camelthorni, is classified as Allomesorhizobium gen. nov. Cluster VI harbored a single symbiotic species M. albiziae and is classified as Neomesorhizobium gen. nov. The remaining seven non-symbiotic members were proposed as: Neoaquamicrobium gen. nov., Manganibacter gen. nov., Ollibium gen. nov., Terribium gen. nov., Kumtagia gen. nov., Borborobacter gen. nov., Aerobium gen. nov.. Furthermore, the genus Corticibacterium is restored and two species in Subcluster IX-1 are reclassified as the member of this genus. CONCLUSION: The Mesorhizobium complex are classified into 15 genera based on phylogenomic analyses and OGRIs of 65 type strains. This study resolved previously non-monophyletic genera in the Mesorhizobium complex.

Salvianolic Acid B Inhibits Oxidative Stress in Glomerular Mesangial Cells Alleviating Diabetic Nephropathy by Regulating SIRT3/FOXO1 Signaling.

INTRODUCTION: Oxidative stress is pivotal in advancing diabetic nephropathy (DN). Salvianolic acid B (SAB), derived from Radix Salviae miltiorrhizae, exhibits renoprotective effects. However, the mechanisms underlying its action in DN are not fully elucidated. This study explores SAB's protective effect on DN, focusing on its antioxidative properties in glomerular mesangial cells. METHODS: The renoprotective effects of various SAB dosages on DN rats were assessed by evaluating kidney tissue pathological alterations through hematoxylin and eosin, periodic acid-Schiff, Masson, TUNEL staining, and kidney function through biochemical detection. Cell counting kit-8 and lactate dehydrogenase cytotoxicity assays were utilized to evaluate the viability of high glucose (HG)-induced HBZY-1 cells treated with various SAB dosages. Oxidative stress and inflammation levels were measured using enzyme-linked immunosorbent assay kits. The Sirtuin 3 (SIRT3)/Forkhead box transcription factor O1 (FOXO1) pathway was examined through Western blot and immunohistochemistry. RESULTS: SAB mitigated kidney histopathological alterations and function and cell apoptosis in DN rats at various dosages. It enhanced the activity of glutathione peroxidase and superoxide dismutase while decreasing reactive oxygen species and malondialdehyde levels both in vivo and in vitro. SAB also suppressed the levels of pro-inflammatory cytokines (IL-1ß, IL-6, MCP-1, and TNF-α) and the expression of collagen IV and fibronectin in HG-induced HBZY-1 cells. Furthermore, SAB activated the SIRT3/FOXO1 signaling pathway. CONCLUSION: Our findings suggest that SAB may alleviate oxidative stress in DN both in vivo and in vitro, potentially through the activation of the SIRT3/FOXO1-mediated signaling pathway. This study provides initial insights into the possible antioxidative and renoprotective effects of SAB, indicating its potential utility as a therapeutic agent for DN.

The mediating role of psychological capital on the relationship between authentic leadership and nurses' caring behavior: a cross-sectional study.

BACKGROUND: Caring behavior among nurses would have an impact on patient outcomes. External organizational job resources and personal internal psychological resources are correlated to nurses' caring behavior. Authentic leadership and psychological capital were shown to be correlated with nurses' caring behavior in previous studies. However, the relationships among the three are nevertheless unclear. This study aimed to examine if psychological capital could act as a mediator between nursing managers' authentic leadership and nurses' caring behavior. METHODS: In December 2021, a total of 3,662 nurses were recruited from 37 hospitals in Anhui Province, China. They filled out online surveys, including general demographic information, the Authentic Leadership Questionnaire, the Psychological Capital Questionnaire, and the Caring Behavior Inventory. Structural Equation Modeling and the bootstrapping procedure were used to examine the mediating role of psychological capital. RESULTS: The scores of authentic leadership, psychological capital, and caring behavior of 3,495 nurses were 52.04 ± 13.24, 96.89 ± 17.78, and 104.28 ± 17.01, respectively. Psychological capital significantly mediated the relationship between authentic leadership and nurses' caring behavior (ß = 0.378, p < 0.001, 95% confidence interval: 0.350 ~ 0.402), which made up 78.75% of the total impact (0.480). CONCLUSION: The findings of this study suggested that nursing managers should develop an authentic leadership style, which can effectively improve nurses' caring behaviors toward patients in clinical practice. Meanwhile, nursing leaders should strengthen nurses' psychological evaluation and training, and promote nurses' caring behavior in clinical settings.

Lignans and Phenylethanoid Glycosides from the Aerial Parts of Pogostemon cablin.

Two new lignans (1-2) and a new octaketide (12), together with twenty-nine known compounds (3-11, 13-32) were isolated and identified from the aerial part of Pogostemon cablin. Their chemical structures were revealed mainly through NMR and MS data. The absolute configuration of 1 and 2 was deduced by comparing its experimental CD with the calculated ECD spectra. The inhibitory activities of the isolated compounds on LPS-stimulated nitric oxide (NO) production in RAW 264.7 cells were investigated. At a concentration of 25 µM, compounds 1 and 11 showed approximately equal NO inhibitory effects to that of aminoguanidine.

Protein extraction from microalgae residue and nutritional assessment.

On the basis of determining isoelectric point of algae residue protein obtained from Scenedesmus dimorphus, this study investigated the effects of pH values, ratio of liquid to solid, extraction temperature and time on protein extraction rates, and assessed the nutritional value of protein extracted from microalgae residues. The results from orthogonal experiments revealed the optimum conditions for extracting proteins from algal residues (pH: 12; liquid-to-solid ratio: 40 mL/g; extraction temperature: 45 ℃; extraction time: 140 min). It was observed that under the optimal conditions, the protein extraction rate was 40.13%. Essential amino acids account for 44.3% of the proteins obtained from algal residues. The content of anti-nutritional factors in algal residues was significantly reduced, and the digestibility of algal residue proteins was higher than the digestibility of algal powder. This indicated that algal residues could be an ideal source of proteins for humans.

(-)-α-Bisabolol Alleviates Atopic Dermatitis by Inhibiting MAPK and NF-κB Signaling in Mast Cell.

(-)-α-Bisabolol (BIS) is a sesquiterpene alcohol derived mostly from Matricaria recutita L., which is a traditional herb and exhibits multiple biologic activities. BIS has been reported for treatment of skin disorders, but the effect of BIS on anti-atopic dermatitis (AD) remains unclear. Therefore, we investigated the effects of BIS on 2,4-dinitrochlorobenzene (DNCB)-induced AD in BALB/c mice and the underlying mechanism in Bone Marrow-Derived Mast Cells (BMMCs). Topical BIS treatment reduced AD-like symptoms and the release of interleukin (IL)-4 without immunoglobulin (Ig)-E production in DNCB-induced BALB/c mice. Histopathological examination revealed that BIS reduced epidermal thickness and inhibited mast cells in the AD-like lesions skin. Oral administration of BIS effectively and dose-dependently suppressed mast-cell-mediated passive cutaneous anaphylaxis. In IgE-mediated BMMCs, the levels of ß-hexosaminidase (ß-hex), histamine, and tumor necrosis factor (TNF)-α were reduced by blocking the activation of nuclear factor-қB (NF-қB) and c-Jun N-terminal kinase (JNK) without P38 mitogen activated protein (P38) and extracellular regulated protein kinases (Erk1/2). Taken together, our experimental results indicated BIS suppresses AD by inhibiting the activation of JNK and NF-κB in mast cells. BIS may be a promising therapeutic agent for atopic dermatitis and other mast-cell-related diseases.

Enhancing CO2 utilization by a physical absorption-based technique in microalgae culture.

Carbon dioxide supplementation is significant for cell growth in autotrophic cultures of microalgae. However, the CO2 utilization efficiency is quite low in most processes. Aimed at this problem, six kinds of physical absorption enhancers were investigated to enhance the biological carbon sequestration of microalgae. By the addition of a small amount of CO2 absorption enhancer, the total inorganic carbon concentration of the medium was significantly increased. In addition, the biomass productivity of Scenedesmus dimorphus was maximally increased by 63% by the addition of propylene carbonate in flask cultures. In cultures using an air-lift photobioreactor equipped with a pH-feedback control system to supply CO2, the CO2 consumption was maximally reduced by 71% with added polyethylene glycol dimethyl ether. This study indicates that the incorporation of physical absorption enhancers could be a promising approach to overcome the problems of low CO2 utilization efficiency and high carbon source cost in algal biomass production.

Longitudinal changes of liver function and hepatitis B reactivation in COVID-19 patients with pre-existing chronic hepatitis B virus infection.

AIM: With the current coronavirus disease (COVID-19) pandemic and high endemic levels of chronic hepatitis B virus (HBV) infection worldwide, it is urgent to investigate liver function changes of COVID-19 patients with chronic HBV infection, and how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in turn affects the course of chronic HBV infection. METHOD: We undertook a retrospective study based on 347 COVID-19 patients (21 vs. 326 with vs. without chronic HBV infection). With the propensity score matching (PSM) method, we yielded 20 and 51 matched patients for the HBV group and the non-HBV group, respectively. RESULTS: At the end of follow-up, all of these 71 patients achieved SARS-CoV-2 clearance (P = 0.1). During the follow-up, 30% versus 31.4% in the HBV group versus non-HBV group progressed to severe COVID-19 (P = 0.97). After PSM, the longitudinal changes of median values for liver biochemistries were not significantly different between the two groups. In the HBV group versus non-HBV group, 35% (7/20) versus 37.25% (19/51) (P = 0.86) had abnormal alanine aminotransferase at least once during hospitalization, 30% (6/20) versus 31.37% (16/51) had abnormal aspartate aminotransferase (P = 0.91), 40% (8/20) versus 37.25% (19/51) had abnormal γ-glutamyltransferase (P = 0.83), and 45% (9/20) versus 39.22% (20/51) had abnormal total bilirubin levels (P = 0.91). Moreover, three patients in the HBV group had hepatitis B reactivation. CONCLUSIONS: Liver dysfunction presented in COVID-19 patients with/without chronic HBV. Moreover, those COVID-19 patients co-infected with chronic HBV could have a risk of hepatitis B reactivation. It is necessary to monitor liver function of COVID-19 patients, as well as HBV-DNA levels for those co-infected with HBV during the whole disease course.

A 26-week 20(S)-ginsenoside Rg3 oral toxicity study in Beagle dogs.

20(s)-ginsenoside Rg3 is a red ginseng-derived compound with the formula C42H72O13 that has been increasingly used by humans, leading to safety concerns regarding this use. In the current study, we conducted a 26-week study during which 20(S)-ginsenoside Rg3 (0, 7, 20, or 60 mg/kg) was continuously administered orally to Beagle dogs in order to explore its toxicity in these animals, with control dogs receiving a vehicle capsule. In total, 10 dogs received each dose of this compound (n = 5 male, n = 5 female per dose). Animals were continuously monitored for a 26-week administration period and a subsequent 4-week follow-up recovery period. At the end of study, we observed no evidence of 20(S)-ginsenoside Rg3 toxicity in clinical indications, body weight, food intake, ophthalmoscopy, electrocardiogram, urinalysis, hematology, serum biochemistry, gross and histopathology findings. However, the kidney relative weight of animals receiving 60 mg/kg of compound was significantly elevated relative to control animals (5.15 ±â€¯0.88‰ vs. 4.11 ±â€¯0.59‰. P < 0.05), and this effect was reversed after 4-week recovery period. Based on these results, the NOAEL value for orally administered 20(S)-ginsenoside Rg3 in dogs is 20 mg/kg.

Phenols and γ-Lactams from the Aerial Part of Pseudolysimachion linariifolium subsp. dilatatum.

Linariifolioside II (1) and (2S)-2-hydroxy-5-oxoproline methyl ester (2), two new compounds along with 13 known compounds were obtained from the aerial part of Pseudolysimachion linariifolium Holub subsp. dilatatum (Nakai & Kitag.) D.Y. Hong. Their chemical structures were revealed mainly through NMR and MS data. The absolute configuration of 2 was deduced by comparing its experimental CD with the calculated ECD spectra. At a concentration of 1 mm, total antioxidant capacities of compounds 1-15 were measured using a rapid ABTS method in vitro. Compounds 1, 3-5, and 11-14 exhibited approximately equal antioxidant capacity to that of vitamin C (Vc).

Cannabinoid receptor-mediated modulation of inhibitory inputs to mitral cells in the main olfactory bulb.

The endocannabinoid (eCB) signaling system has been functionally implicated in many brain regions. Our understanding of the role of cannabinoid receptor type 1 (CB1) in olfactory processing remains limited. Cannabinoid signaling is involved in regulating glomerular activity in the main olfactory bulb (MOB). However, the cannabinoid-related circuitry of inputs to mitral cells in the MOB has not been fully determined. Using anatomical and functional approaches we have explored this question. CB1 was present in periglomerular processes of a GAD65-positive subpopulation of interneurons but not in mitral cells. We detected eCBs in the mouse MOB as well as the expression of CB1 and other genes associated with cannabinoid signaling in the MOB. Patch-clamp electrophysiology demonstrated that CB1 agonists activated mitral cells and evoked an inward current, while CB1 antagonists reduced firing and evoked an outward current. CB1 effects on mitral cells were absent in subglomerular slices in which the olfactory nerve layer and glomerular layer were removed, suggesting the glomerular layer as the site of CB1 action. We previously observed that GABAergic periglomerular cells show the inverse response pattern to CB1 activation compared with mitral cells, suggesting that CB1 indirectly regulates mitral cell activity as a result of cellular activation of glomerular GABAergic processes . This hypothesis was supported by the finding that cannabinoids modulated synaptic transmission to mitral cells. We conclude that CB1 directly regulates GABAergic processes in the glomerular layer to control GABA release and, in turn, regulates mitral cell activity with potential effects on olfactory threshold and behavior.NEW & NOTEWORTHY Cannabinoid signaling with cannabinoid receptor type 1 (CB1) is involved in the regulation of glomerular activity in the main olfactory bulb (MOB). We detected endocannabinoids in the mouse MOB. CB1 was present in periglomerular processes of a GAD65-positive subpopulation of interneurons. CB1 agonists activated mitral cells. CB1 directly regulates GABAergic processes to control GABA release and, in turn, regulates mitral cell activity with potential effects on olfactory threshold and behavior.

Self-Assembled and Size-Controllable Oligonucleotide Nanospheres for Effective Antisense Gene Delivery through an Endocytosis-Independent Pathway.

The development of efficient gene delivery vectors has faced two major challenges, namely endo- and lysosomal escape and intracellular release. To address these problems, we developed an oligonucleotide (ON)-template-assisted polymerization approach to create ON nanospheres as gene vectors. Guanidinium-containing disulfide monomers were organized on the ON templates to increase their effective local concentrations. Consequently, ring-opening disulfide-exchange polymerization between monomers was accelerated, further facilitating the self-assembly of ON nanospheres. The size of these nanospheres was controlled by varying the length of the ON templates. Importantly, the nanospheres can be directly delivered into the cytosol through an endocytosis-independent pathway, which is followed by intracellular depolymerization in the reductive cytosolic environment to release the packaged ONs, resulting in efficient gene silencing. The ON nanospheres thus hold great promise as candidates for gene therapy.

Amplified Visualization of Protein-Specific Glycosylation in Zebrafish via Proximity-Induced Hybridization Chain Reaction.

The visualization of glycosylation states of specific proteins in vivo is of great importance for uncovering their roles in disease development. However, the ubiquity of glycosylation makes probing the glycans on a certain protein as difficult as looking for a needle in a haystack. Herein, we demonstrate a proximity-induced hybridization chain reaction (HCR) strategy for amplified visualization of protein-specific glycosylation. The strategy relies on designing two kinds of DNA probes, glycan conversion probes and protein recognition probes, which are attached to glycans and target proteins, respectively. Upon sequential binding to the targets, the proximity-induced hybridization between two probes occurs, which leads to the structure-switching of protein recognition probes, followed by triggering of HCR assembly. This strategy has been used to visualize tyrosine-protein kinase 7-specific sialic acid in living CEM cells and zebrafish and to monitor its variation during drug treatment. It provides a potential tool for investigating protein-specific glycosylation and researching the relation between dynamic glycans state and disease process.

miRNAs expression profile in bast of ramie elongation phase and cell wall thickening and end wall dissolving phase.

MicroRNAs (miRNAs) are 20-24 nucleotide long non-coding RNAs that play critical regulatory roles during plant development, organ morphogenesis, and cell fate determination and differentiation. In this study, miRNA microarray chips were used to explore the expression profile of ramie miRNAs between the bast of fiber elongation phase and those of cell wall thickening and end wall dissolving phase. There are 150 and 148 credible miRNAs in the bast of fiber elongation phase and cell wall thickening and end wall dissolving phase, respectively. These miRNAs distributed in 27 species and mainly concentrated in nine species. Analysis showed that 51 miRNAs were differentially expressed: 27 up-regulated (miR166, miR172, miR396, miR482, miR894 and miR2911 families) and 24 down-regulated (miR156, miR159, miR164, miR319 and miR1450 families) in the bast of fiber elongation phase compared with the bast of cell wall thickening and end wall dissolving phase. To further confirm our results, we examined the expression of three miRNAs (zma-miR172b*, pvu-miR482 and vvi-172a) by quantitative real-time reverse transcriptase-PCR. Our results will provide a molecular basis for future research miRNA function on ramie genetics and breeding.

[Endophytic bacterial community in the symptoms and symptomless tissues of HLB-affected citrus plant].

OBJECTIVE: To analyze the endophytic bacteria in symptoms and symptomless tissues, reveal dominant bacterial population which may interact with Ca. Las. METHOD: The population structure and diversity of endophytic bacteria in symptoms and symptomless tissues of single HLB-affected citrus plant were studied based on 16S rDNA sequences analyzed by PCR-DGGE (PCR-denaturing gradient gel electrophoresis). Quantitative analysis of Ca. Las, dominant bacteria and total amount of bacterial population in symptoms and symptomless tissues of branches, leaves and fruits was done by quantitative PCR. RESULT: The amount of Ca. Las is significantly different in symptoms and symptomless tissues; bacterial population in symptoms citrus tissues was significantly higher than in symptomless tissues. PCR-DGGE analysis result shows that endophytic bacterial structures are basically the same in symptoms and symptomless tissues. Extraction, cloning and sequencing of 17 obvious bands in DGGE electrophoretogram reveal that 8 of 17 bands belonged to the genus Serratia, which accounted for 47.06%. Sequence alignment shows that they belonged to different strains of Serratia marcescens with the 99.63% similarity. Quantitative analysis of the total bacteria and Serratia marcescens shows that there is no significant difference in total bacterial count between symptoms and symptomless tissues whereas the amount of Serratia marcescens was negatively correlated with the amount of Las. CONCLUSION: The Ca. Las is heterogeneously distributed among various tissues of HLB-affected citrus plant. The amount of Ca. Las was negatively correlated with Serratia marcescens and total amount of endophytic bacteria have no relevance with symptom of HLB disease. How the interaction of Serratia marcescens and Ca. Las in tissue of citrus needs further study.

Enzymatic biosynthesis of D-galactose derivatives: Advances and perspectives.

D-Galactose derivatives, including galactosyl-conjugates and galactose-upgrading compounds, provide various physiological benefits and find applications in industries such as food, cosmetics, feed, pharmaceuticals. Many research on galactose derivatives focuses on identification, characterization, development, and mechanistic aspects of their physiological function, providing opportunities and challenges for the development of practical approaches for synthesizing galactose derivatives. This study focuses on recent advancements in enzymatic biosynthesis of galactose derivatives. Various strategies including isomerization, epimerization, transgalactosylation, and phosphorylation-dephosphorylation were extensively discussed under the perspectives of thermodynamic feasibility, theoretical yield, cost-effectiveness, and by-product elimination. Specifically, the enzymatic phosphorylation-dephosphorylation cascade is a promising enzymatic synthesis route for galactose derivatives because it can overcome the thermodynamic equilibrium of isomerization and utilize cost-effective raw materials. The study also elucidates the existing challenges and future trends in enzymatic biosynthesis of galactose derivatives. Collectively, this review provides a real-time summary aimed at promoting the practical biosynthesis of galactose derivatives through enzymatic catalysis.

The mediating role of psychological capital on the relationship between authentic leadership and innovative behaviour among Chinese nurses.

AIM: To explore the mediating role of psychological capital between authentic leadership and innovative behaviour among Chinese nurses. DESIGN: A cross-sectional study. METHODS: In December 2021, online surveys were delivered among nurses from 37 hospitals in Anhui Province by convenience sampling approach. The data was collected using the Chinese version of the Authentic Leadership Questionnaire, Nurse Psychological Capital Questionnaire and Nurse Innovative Behaviour Scale. The structural equation model and bootstrap test examined the mediating role of psychological capital between authentic leadership and innovative behaviour. RESULTS: 3495 Chinese nurses from 37 Anhui Province hospitals participated in this study. The mean item score of authentic leadership was 3.25 (SD 0.83), psychological capital was 4.85 (SD 0.89), and innovative behaviour was 2.82 (SD 0.84). Authentic leadership perceived by nurses, psychological capital, and innovative behaviour were statistically significant and positively correlated with each other (r = 0.524 ~ 0.806, p < 0.01). Psychological capital significantly mediated the association between authentic leadership and innovative behaviour (ß = 0.449, p < 0.001), and its mediating effect accounted for 76.75% of the total effect. CONCLUSION: Results suggest the importance of developing nurse managers' authentic leadership to foster nurses' psychological capital and innovation behaviour.

Levels of antibodies against the monkeypox virus compared by HIV status and historical smallpox vaccinations: a serological study.

Men who have sex with men and people living with HIV are disproportionately affected in the 2022 multi-country monkeypox epidemic. The smallpox vaccine can induce cross-reactive antibodies against the monkeypox virus (MPXV) and reduce the risk of infection. Data on antibodies against MPXV induced by historic smallpox vaccination in people with HIV are scarce. In this observational study, plasma samples were collected from people living with and without HIV in Shenzhen, China. We measured antibodies binding to two representative proteins of vaccinia virus (VACV; A27L and A33R) and homologous proteins of MPXV (A29L and A35R) using an enzyme-linked immunosorbent assay. We compared the levels of these antibodies between people living with and without HIV. Stratified analyses were performed based on the year of birth of 1981 when the smallpox vaccination was stopped in China. Plasma samples from 677 people living with HIV and 746 people without HIV were tested. A consistent pattern was identified among the four antibodies, regardless of HIV status. VACV antigen-reactive and MPXV antigen-reactive antibodies induced by historic smallpox vaccination were detectable in the people born before 1981, and antibody levels reached a nadir during or after 1981. The levels of smallpox vaccine-induced antibodies were comparable between people living with HIV and those without HIV. Our findings suggest that the antibody levels against MPXV decreased in both people living with and without HIV due to the cessation of smallpox vaccination.

Cannabinoid receptor-mediated regulation of neuronal activity and signaling in glomeruli of the main olfactory bulb.

Cannabinoid receptors (CB1Rs) are present in glomeruli of the main olfactory bulb. The functions of CB1Rs and their endogenous activators, endocannabinoids, for glomerular signaling are unknown. Glomeruli contain at least three types of neurons: periglomerular (PG), external tufted (ET), and short-axon (SA) cells. PG cells form inhibitory GABAergic dendrodendritic synapses with ET cells. ET cells form excitatory glutamatergic dendrodendritic synapses with PG and SA cells. In mouse brain slices, we used whole-cell patch-clamp recordings to study the role of CB1Rs in regulating PG and ET cells. Cannabinoids displayed strong, direct inhibitory effects on PG cells and weak effects on ET cells. Single pulses or a train of pulses of depolarizing current injected into an ET cell evoked suppression of IPSCs. This suggests retrograde endocannabinoid signaling, namely, depolarization-induced suppression of inhibition (DSI) in ET cells. Our results support the hypothesis that burst firing of ET cells triggers the release of endocannabinoids which in turn directly inhibit PG cells and reduce GABA release from PG cells. This, in turn, can result in a transient reduction of PG cell inhibitory input to ET cells.

Different clinical guidelines, common goal: To reduce COVID-19 mortality.

The tendency of the Omicron variant to rapidly became the dominant SARS-CoV-2 strain and its weaker virulence than other strains worldwide has prompted many countries to adjust their public health strategies. This work summarizes all appropriate clinical interventions to reduce the public health burden caused by COVID-19 according to guidelines from the World Health Organization and 10 countries, i.e., the United States of America (USA), India, France, Germany, Brazil, South Korea, Japan, Italy, the United Kingdom (UK), and China. Five stages of COVID-19 were identified: asymptomatic infection and mild, moderate, severe, and critical illness. Most guidelines recommend antivirals starting with mild cases for those from Germany and India. Since more drugs are being developed and are becoming available to COVID-19 patients, guidelines are increasingly being updated with new pharmacological intervention strategies. Thus, a global view needs to be adopted to provide helpful options and precise treatment strategies during the lasting fight against the COVID-19 pandemic.