Seismic Constraint From Vp/Vs Ratios on the Structure and Composition Across the Continent‐Ocean Transition Zone, South China Sea

At non-volcanic passive continental margins, seismic techniques often failed to uniquely define the nature of crustal domains. Here, we overcome this problem by studying the structure and composition of the continent-ocean transition (COT) in the Southwest Sub-basin of the South China Sea, using P and S wave seismic tomography and Vp/Vs ratios, providing unique constraints on lithology. Throughout the image domain, we can rule out large areas of exhumed mantle as Vp/Vs ratios are always <1.9 in the shallow basement layer. Instead, the COT is characterized by extended and fragmented continental crust, and possibly mafic aggregation at the bottom of the crust. In concert with observations from multichannel seismic reflection data, seismic velocities and Vp/Vs ratios suggest that the oldest oceanic crust was formed by starved magmatism, causing rugged basement, thin crust, nearly absent lower crust, and moderately serpentinized mantle below. Our results reveal that rifting occurred without un-roofing continental mantle

Glycyrrhiza uralensis polysaccharides ameliorates cecal ligation and puncture-induced sepsis by inhibiting the cGAS-STING signaling pathway

Ethnopharmacological relevance:G. uralensis Fisch. (Glycyrrhiza uralensis) is an ancient and widely used traditional Chinese medicine with good efficacy in clearing heat and detoxifying action. Studies suggest that Glycyrrhiza Uralensis Polysaccharides (GUP), one of the major components of G. uralensis, has anti-inflammatory, anti-cancer and hepatoprotective effects., but its exact molecular mechanism has not been explored in depth.Aim of the study: Objectives of our research are about exploring the anti-inflammatory role of GUP and the mechanisms of its action.Materials and methods: ELISA kits, Western blotting, immunofluorescence, quantitative real-time PCR, immunoprecipitation and DMXAA-mediated STING activation mice models were performed to investigate the role of GUP on the cGAS-STING pathway. To determine the anti-inflammatory effects of GUP, cecal ligation and puncture (CLP) sepsis models were employed.Results: GUP could effectively inhibit the activation of the cGAS-STING signaling pathway accompany by a decrease the expression of type I interferon-related genes and inflammatory factors in BMDMs, THP-1, and human PBMCs. Mechanistically, GUP does not affect the oligomerization of STING, but affects the interaction of STING with TBK1 and TBK1 with IRF3. Significantly, GUP had great therapeutic effects on DMXAA-induced agonist experiments in vivo as well as CLP sepsis in mice.Conclusion: Our studies suggest that GUP is an effective inhibitor of the cGAS-STING pathway, which may be a potential medicine for the treatment of inflammatory diseases mediated by the cGAS-STING pathway

Increased macrolide resistance rate of Mycoplasma pneumoniae correlated with epidemic in Beijing, China in 2023

We collected respiratory specimens from 128 pediatric patients diagnosed with pneumonia in Beijing in late 2023. Mycoplasma pneumoniae was detected in 77.3% (99/128) patients, with 36.4% (4/11), 82.9% (34/41), 80.3% (61/76) in children aged less than 3 years, 3–6 years, over 7 years, respectively. Mycoplasma pneumoniae (M. pneumoniae) was characterized using P1 gene typing, MLVA typing and sequencing of domain V of the 23S rRNA gene. P1 gene type 1 (P1-1; 76.1%, 54/71) and MLVA type 4-5-7-2 (73.7%, 73/99) were predominant. MLVA identified a new genotype: 3–4–6-2. Macrolide resistance-associated mutations were detected in 100% of samples, with A2063G accounting for 99% and A2064G for 1%. The positive rate of M. pneumoniae was higher compared to previous reports, especially in children less than 3 years, suggesting a M. pneumoniae epidemic showing a younger age trend occurred in late 2023 in Beijing, China. Higher proportions of macrolide-resistant M. pneumoniae, P1-1 and 4-5-7-2 genotype M. pneumoniae indicated increased macrolide resistance rate and genotyping shift phenomenon, which might be attributable to this epidemic. Additionally, complete clinical information from 73 M. pneumoniae pneumonia inpatients were analyzed. The incidence of severe M. pneumoniae pneumonia was 56.2% (41/73). Mycoplasma pneumoniae pneumonia patients exhibited longer duration of fever, with a median value of 10.0 days (IQR, 8.0–13.0), and higher incidence of complications (74.0%, 54/73). However, in this cohort, we found that the severity of M. pneumoniae pneumonia, co-infection, or complications were not associated with M. pneumoniae P1 gene or MLVA types. Clinicians should be aware that patients infected with macrolide-resistant M. pneumoniae exhibited more severe clinical presentations

Impact of Germination Time on Resveratrol, Phenolic Acids, and Antioxidant Capacities of Different Varieties of Peanut (Arachis hypogaea Linn.) from China

In China, peanut sprouts are popular among consumers as functional vegetables. This study reports the change in total phenolic content (TPC), total flavonoid content (TFC), monomeric anthocyanin content (MAC), vitamin C, trans-resveratrol content, antioxidant capacities, and phenolic profile of three different varieties of peanut during 8 days of germination. The TPC, TFC, and antioxidant capacity of peanut samples were reduced and then increased with an increase in germination time. TFC values were highly correlated with 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) values. MAC values of peanuts were first increased and then decreased during 8 days of germination. The TFC, DPPH, and FRAP values of germinated peanuts were lower compared to the non-germinated peanut. Germination of peanut samples enhanced the total phenolic acids and trans-resveratrol content, but the vitamin C content of peanut sprouts was lower than ungerminated peanuts

Selective construction of dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] via three-component reaction

A convenient synthetic procedure for the construction of novel dispirooxindole motifs was successfully developed by base-promoted three-component reaction of ammonium acetate, isatins and in situ-generated 3-isatyl-1,4-dicarbonyl compounds. The piperidine-promoted three-component reaction of ammonium acetate, isatins and the in situ-generated dimedone adducts of 3-ethoxycarbonylmethyleneoxindoles afforded mutlifunctionalized dispiro[indoline-3,2'-quinoline-3',3''-indoline] derivatives in good yields and with high diastereoselectivity. On the other hand, a similar reaction of the dimedone adducts of 3-phenacylideneoxindoles afforded unique dispiro[indoline-3,2'-pyrrole-3',3''-indoline] derivatives with a cyclohexanedione substituent. A plausible reaction mechanism is proposed to explain the formation of the different spirooxindoles

Allisartan ameliorates vascular remodeling through regulation of voltage-gated potassium channels in hypertensive rats

Abstract Background The objective of the present study was to determine the effect of allisartan, a new angiotensin II type 1 receptor antagonist on vascular remodeling through voltage gated potassium channels (Kv7) in hypertensive rats. Methods The study included a total of 47 Sprague Dawley (SD) rats. The animals were randomized to sham operation (n = 14), untreated hypertensive control group (n = 18) and allisartan treatment group (n = 15). Using renal artery stenosis, hypertension was induced in animals. Single dose of allisartan was administered intra-gastrically to animals in the allisartan treatment group and match placebo in the other 2 groups. Wire myography was used to measure the muscle tension in isolated mesenteric arteries from the animals. Real-time polymerase chain reaction was used to quantify the expression of Kv7 channel mRNA subunits. Results After 4 weeks of treatment, a significant decrease in mean arterial, systolic and diastolic blood pressure (SBP and DBP) was observed in allisartan treatment group compared to hypertension control group. The median arterial wall thickness and area/diameter ratio reduced significantly in treatment group compared to untreated hypertension group (P < 0.05). Wire myography demonstrated increased relaxation of mesenteric artery with increase in concentration of ML213. A significant up-regulation in the expression of all Kv7 mRNA subunits was observed in allisartan group compared to untreated hypertension group. Conclusions From the results, allisartan was found to lower BP and preserve vascular remodeling through Kv7 channels

Arachidonic Acid Cascade and Eicosanoid Production Are Elevated While LTC4 Synthase Modulates the Lipidomics Profile in the Brain of the HIVgp120-Transgenic Mouse Model of NeuroHIV

Background: Combination antiretroviral therapy (cART) has transformed HIV infection from a terminal disease to a manageable chronic health condition, extending patients’ life expectancy to that of the general population. However, the incidence of HIV-associated neurocognitive disorders (HANDs) has persisted despite virological suppression. Patients with HIV display persistent signs of immune activation and inflammation despite cART. The arachidonic acid (AA) cascade is an important immune response system responsible for both pro- and anti-inflammatory processes. Methods: Lipidomics, mRNA and Western blotting analysis provide valuable insights into the molecular mechanisms surrounding arachidonic acid metabolism and the resulting inflammation caused by perturbations thereof. Results: Here, we report the presence of inflammatory eicosanoids in the brains of a transgenic mouse model of NeuroHIV that expresses soluble HIV-1 envelope glycoprotein in glial cells (HIVgp120tg mice). Additionally, we report that the effect of LTC4S knockout in HIVgp120tg mice resulted in the sexually dimorphic transcription of COX- and 5-LOX-related genes. Furthermore, the absence of LTC4S suppressed ERK1/2 and p38 MAPK signaling activity in female mice only. The mass spectrometry-based lipidomic profiling of these mice reveals beneficial alterations to lipids in the brain. Conclusion: Targeting the AA cascade may hold potential in the treatment of neuroinflammation observed in NeuroHIV and HANDs

Distal regulatory elements identified by methylation and hydroxymethylation haplotype blocks from mouse brain

Abstract Background 5-Hydroxymethylcytosine (5hmC) is an oxidation product of 5-methylcytosine (5mC), and adjacent CpG sites in mammalian genome can be co-methylated and co-hydroxymethylated due to the processivity of DNMT and TET enzymes. Results We applied TAB-seq and oxBS-seq to selectively detect 5hmC and 5mC at base resolution in the mouse cortex, olfactory bulb and cerebellum tissues. We found that majority of the called 5hmC CpG sites frequently have 5mC modification simultaneously and are enriched in gene body regions of neuron development-related genes in brain tissues. Strikingly, by a systematic search of regions that show highly coordinated methylation and hydroxymethylation (MHBs and hMHBs), we found that MHBs significantly overlapped with hMHBs in gene body regions. Moreover, using a metric called methylation haplotype load, we defined a subset of 1361 tissue-specific MHBs and 3818 shared MHBs. Shared MHBs with low MHL correspond with developmental enhancers, and tissue-specific MHBs resemble the regulatory elements for tissue identity. Conclusions Our results provide new insights into the role of coordinately oxidized 5mC to 5hmC as distal regulatory elements may involve in regulating tissue identity