Targeted association mapping demonstrating the complex molecular genetics of fatty acid formation in soybean

Palmitic acid bi-alleles of Map-6064 in three subpopulations. (TIFF 1235 kb

Heat Shock Protein 70 Protects the Heart from Ischemia/Reperfusion Injury through Inhibition of p38 MAPK Signaling.

BackgroundHeat shock protein 70 (Hsp70) has been shown to exert cardioprotection. Intracellular calcium ([Ca2+]i) overload induced by p38 mitogen-activated protein kinase (p38 MAPK) activation contributes to cardiac ischemia/reperfusion (I/R) injury. However, whether Hsp70 interacts with p38 MAPK signaling is unclear. Therefore, this study investigated the regulation of p38 MAPK by Hsp70 in I/R-induced cardiac injury.MethodsNeonatal rat cardiomyocytes were subjected to oxygen-glucose deprivation for 6 h followed by 2 h reoxygenation (OGD/R), and rats underwent left anterior artery ligation for 30 min followed by 30 min of reperfusion. The p38 MAPK inhibitor (SB203580), Hsp70 inhibitor (Quercetin), and Hsp70 short hairpin RNA (shRNA) were used prior to OGD/R or I/R. Cell viability, lactate dehydrogenase (LDH) release, serum cardiac troponin I (cTnI), [Ca2+]i levels, cell apoptosis, myocardial infarct size, mRNA level of IL-1β and IL-6, and protein expression of Hsp70, phosphorylated p38 MAPK (p-p38 MAPK), sarcoplasmic/endoplasmic reticulum Ca2+-ATPase2 (SERCA2), phosphorylated signal transducer and activator of transcription3 (p-STAT3), and cleaved caspase3 were assessed.ResultsPretreatment with a p38 MAPK inhibitor, SB203580, significantly attenuated OGD/R-induced cell injury or I/R-induced myocardial injury, as evidenced by improved cell viability and lower LDH release, resulted in lower serum cTnI and myocardial infarct size, alleviation of [Ca2+]i overload and cell apoptosis, inhibition of IL-1β and IL-6, and modulation of protein expressions of p-p38 MAPK, SERCA2, p-STAT3, and cleaved-caspase3. Knockdown of Hsp70 by shRNA exacerbated OGD/R-induced cell injury, which was effectively abolished by SB203580. Moreover, inhibition of Hsp70 by quercetin enhanced I/R-induced myocardial injury, while SB203580 pretreatment reversed the harmful effects caused by quercetin.ConclusionsInhibition of Hsp70 aggravates [Ca2+]i overload, inflammation, and apoptosis through regulating p38 MAPK signaling during cardiac I/R injury, which may help provide novel insight into cardioprotective strategies

Effects of painful stimulation and acupuncture on attention networks in healthy subjects

Pain is a subjective sensory and emotional experience, and it has been reported that many different brain regions are regulated by pain, and that pain can impact attention. Acupuncture is an important treatment component of Chinese traditional medicine, and has been used for thousands of years to treat a wide variety of conditions. Although several studies have shown that acupuncture improves consciousness, the precise impact of both acupuncture and painful stimulation on attention is unclear. Are all of the attention networks modulated, or do these stimuli act on a specific network? Is the effect of painful stimulation similar to that of acupuncture? We administered the attention network test to 30 participants (15 males) to investigate the relative efficiencies of three independent attention networks (alerting, orienting, and executive control networks) under three conditions: baseline, after painful stimulation, and after acupuncture. The degree of pain experienced was assessed on a horizontally oriented visual analogue scale. The results showed that painful stimulation and acupuncture had similar effects on the orienting and executive control networks; however, there was a significantly different effect between the three conditions on the alerting network. In conclusion, (1) painful stimulation can selectively impact attention; (2) acupuncture can also selectively impact attention; i.e., both have selective influences on the alerting and executive control networks, but not on the orienting network; (3) the effects of acupuncture and painful stimulation are not identical. The mechanisms by which painful stimulation and acupuncture influence attention warrant further research

(E)-1-(2,4-Dihy­droxy­phen­yl)-3-(4-hydroxy­phen­yl)prop-2-en-1-one monohydrate

In the title compound, C15H12O4·H2O, the two benzene rings are not coplanar, making a dihedral angle of 7.24 (16)°. An intra­molecular hy­droxy–carbonyl O—H⋯O hydrogen bond occurs. In the crystal, four inter­molecular O—H⋯O hydrogen bonds involving the hy­droxy residues, the carbonyl group and the water mol­ecule lead to the formation of a three-dimensional network. The supra­molecular structure is further stabilized by weak C—H⋯O inter­actions

Comparison of the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children and adolescents with newly diagnosed focal epilepsy

Objective: This study aims to compare the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children with focal epilepsy (FE).Methods: This is an ambispective, single-center, non-inferiority study comparing the effectiveness and safety of perampanel (PER) monotherapy and oxcarbazepine (OXC) monotherapy in children with newly diagnosed FE. The primary endpoint was a six-month seizure freedom rate. The secondary endpoints included retention, responder, and seizure freedom rates at 3, 6, and 12 months, respectively. Adverse events (AEs) were also recorded for both groups.Results: One hundred and thirty children and adolescents aged from 4 to 18years newly diagnosed with FE between May 2020 and November 2022 in Wuhan Children’s Hospital were included. There were 71 patients in the PER group and 59 patients in the OXC group. In the per protocol set (PPS), 50 (78.1%) in the PER group and 43 (78.2%) in the OXC group completed six months of treatment without seizures. The lower 95% CI (66.0%–87.5%) limit of PER was higher than the non-inferiority margin of 62.4% (80% of the 6-month seizure freedom rate in the OXC group); PER was non-inferior to OXC. The 3-month and 12-month seizure freedom rates were 77.1% and 82.9% for the PER group, respectively, while they were 80.4% and 75.8% for the OXC group. There were no serious adverse events in both groups.Conclusion: PER showed comparable effectiveness and safety compared with OXC in children with newly diagnosed focal epilepsy, which might be an effective and safe treatment for children and adolescents with newly diagnosed FE.Clinical Trial Registration: Identifier ChiCTR230007469

Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells.

Chromatin architecture has been implicated in cell type-specific gene regulatory programs, yet how chromatin remodels during development remains to be fully elucidated. Here, by interrogating chromatin reorganization during human pluripotent stem cell (hPSC) differentiation, we discover a role for the primate-specific endogenous retrotransposon human endogenous retrovirus subfamily H (HERV-H) in creating topologically associating domains (TADs) in hPSCs. Deleting these HERV-H elements eliminates their corresponding TAD boundaries and reduces the transcription of upstream genes, while de novo insertion of HERV-H elements can introduce new TAD boundaries. The ability of HERV-H to create TAD boundaries depends on high transcription, as transcriptional repression of HERV-H elements prevents the formation of boundaries. This ability is not limited to hPSCs, as these actively transcribed HERV-H elements and their corresponding TAD boundaries also appear in pluripotent stem cells from other hominids but not in more distantly related species lacking HERV-H elements. Overall, our results provide direct evidence for retrotransposons in actively shaping cell type- and species-specific chromatin architecture

Selection of Pru p 3 hypoallergenic peach and nectarine varieties

To the Editor, Peach is an important fruit consumed worldwide. However, it is also one of the most frequently reported allergenic fruits.1 Component diagnosis of peach allergy indicates Pru p 1, Pru p 2, Pru p 3, Pru p 4, Pru p 7, and Pru p 9 are involved.2, 3 Pru p 3 is the dominant allergen responsible for severe allergic reaction,4 and it is considered to be the primary sensitizer to other LTPs in Mediterranean and Central Europe.5 The levels of Pru p 3 differ between varieties.6 To date, measurement of Pru p 3 in a limited number of peach and nectarines from Spain, United States, and Italy has been reported.7 Significant variation of allergen concentration in processed foods containing peach has also been observed.8 The content of Pru p 3 of peach/nectarine determines the potential risk for peach allergic patients. China is the origin of peach with representative genetic diversity to be explored for hypoallergenic varieties.9 A core collection of 103 varieties cultivated in Jiaxing, Zhejiang Province were selected to represent this diversity, including 23 nectarines and 80 peach varieties (with fruit hair, round or flat, 77 cultivated, three wild) (Table S1). The soluble solid content (SSC), ripening date, and peach aroma intensity were recorded. Specific methods are detailed in the Supporting Information. Pru p 3 was quantified by ELISA based on our previous research.6info:eu-repo/semantics/publishedVersio

Therapeutic effects of total saikosaponins from Radix bupleuri against Alzheimer’s disease

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by memory loss and cognitive dysfunction in the elderly, with amyloid-beta (Aβ) deposition and hyperphosphorylation of tau protein as the main pathological feature. Nuclear factor 2 (Nrf2) is a transcription factor that primarily exists in the cytosol of hippocampal neurons, and it is considered as an important regulator of autophagy, oxidative stress, and inflammation. Total saikosaponins (TS) is the main bioactive component of Radix bupleuri (Chaihu). In this study, it was found that TS could ameliorate cognitive dysfunction in APP/PS1 transgenic mice and reduce Aβ generation and senile plaque deposition via activating Nrf2 and downregulating the expression of β-secretase 1 (BACE1). In addition, TS can enhance autophagy by promoting the expression of Beclin-1 and LC3-II, increasing the degradation of p62 and NDP52 and the clearance of phosphorylated tau (p-tau), and reducing the expression of p-tau. It can also downregulate the expression of nuclear factor-κB (NF-κB) to inhibit the activation of glial cells and reduce the release of inflammatory factors. In vitro experiments using PC12 cells induced by Aβ, TS could significantly inhibit the aggregation of Aβ and reduce cytotoxicity. It was found that Nrf2 knock-out weakened the inhibitory effect of TS on BACE1 and NF-κB transcription in PC12 cells. Moreover, the inhibitory effect of TS on BACE1 transcription was achieved by promoting the binding of Nrf2 and the promoter of BACE1 ARE1. Results showed that TS downregulated the expression of BACE1 and NF-κB through Nrf2, thereby reducing the generation of Aβ and inhibiting neuroinflammation. Furthermore, TS can ameliorate synaptic loss and alleviate oxidative stress. In gut microbiota analysis, dysbiosis was demonstrated in APP/PS1 transgenic mice, indicating a potential link between gut microbiota and AD. Furthermore, TS treatment reverses the gut microbiota disorder in APP/PS1 mice, suggesting a therapeutic strategy by remodeling the gut microbe. Collectively, these data shows that TS may serve as a potential approach for AD treatment. Further investigation is needed to clarify the detailed mechanisms underlying TS regulating gut microbiota and oxidative stress