Cell lineage-specific mitochondrial resilience during mammalian organogenesis.

Mitochondrial activity differs markedly between organs, but it is not known how and when this arises. Here we show that cell lineage-specific expression profiles involving essential mitochondrial genes emerge at an early stage in mouse development, including tissue-specific isoforms present before organ formation. However, the nuclear transcriptional signatures were not independent of organelle function. Genetically disrupting intra-mitochondrial protein synthesis with two different mtDNA mutations induced cell lineage-specific compensatory responses, including molecular pathways not previously implicated in organellar maintenance. We saw downregulation of genes whose expression is known to exacerbate the effects of exogenous mitochondrial toxins, indicating a transcriptional adaptation to mitochondrial dysfunction during embryonic development. The compensatory pathways were both tissue and mutation specific and under the control of transcription factors which promote organelle resilience. These are likely to contribute to the tissue specificity which characterizes human mitochondrial diseases and are potential targets for organ-directed treatments.

Atramacronoid A induces the PANoptosis-like cell death of human breast cancer cells through the CASP-3/PARP-GSDMD-MLKL pathways.

Breast cancer is the most common malignant tumor and a major cause of mortality among women worldwide. Atramacronoid A (AM-A) is a unique natural sesquiterpene lactone isolated from the rhizome of Atractylodes macrocephala Koidz (known as Baizhu in Chinese). Our study demonstrated that AM-A triggers a specific form of cell death resembling PANoptosis-like cell death. Further analysis indicated that AM-A-induced PANoptosis-like cell death is associated with the CASP-3/PARP-GSDMD-MLKL pathways, which are mediated by mitochondrial dysfunction. These results suggest the potential of AM-A as a lead compound and offer insights for the development of therapeutic agents for breast cancer from natural products.

New caffeoyl derivatives with potent DPPH radical scavenging activity from Elephantopus tomentosus.

Eight new caffeoyl derivatives, elephantomentosides A-H (1 - 8), together with ten known ones (9 - 18), were isolated from the whole plant of Elephantopos tomentosus L. Their structures were elucidated using detailed spectroscopic analysis. Structurally, compounds 1 - 8 are composed of ß-D-glucopyranose, and almost all of the substituent positions are at the C-1' and C-4' of glucopyranose. The anti-inflammatory and antioxidant activities of all isolated compounds were evaluated in vitro. Compounds 9-10, 13-15, and 17-18 exhibited significant DPPH scavenging capacity with IC50 values in the range of 10.01-25.07 µM, in comparison with Vc (IC50, 17.98 µM).

Mediating effect of psychological capital on the relationship between mental health literacy and coping styles among newly recruited nurses.

BACKGROUND: Newly recruited nurses face multiple sources of stress and their coping styles need to be focused on to ensure good mental health. This study aimed to examine the relationship among mental health literacy, psychological capital and coping styles in newly recruited nurses. METHODS: A cross-sectional study was conducted in August and September 2022. A total of 315 newly recruited nurses were recruited in a tertiary hospital in Henan Province, central China, employing the convenience sampling method. The self-reported questionnaires were sent through a QR code, including the Mental Health Literacy Scale for Healthcare Students, Psychological Capital Questionnaire, and Simplified Coping Style Questionnaire. Pearson correlation analysis was used to evaluate the relationships among the variables. Mediation analysis was performed to identify the mediating effect of psychological capital on the relationship between mental health literacy and coping styles. RESULTS: Positive coping showed a positive relationship with psychological capital and mental health literacy, while negative coping showed a negative relationship with psychological capital and mental health literacy. For positive coping, psychological capital was a partial mediator with an effect of 0.140, accounting for 62.8%. For negative coping, a full mediating effect was shown by psychological capital between mental health literacy and negative coping, with an indirect effect of -0.048. CONCLUSION: Psychological capital plays a partial and complete mediating role between mental health literacy and different coping styles among newly recruited nurses. Diversified training and personalized guidance in improving mental health literacy and increasing psychological capital simultaneously can be provided to newly recruited nurses continuously to adjust their coping styles.

Hourglass-Shaped Nanocages with Concaved Structures Based on Selective Self-Complementary Coordination Ligands and Tunable Hierarchical Self-Assembly.

Three-dimensional (3D) structures constructed via coordination-driven self-assemblies have recently garnered increasing attention due to the challenges in structural design and potential applications. In particular, developing new strategy for the convenient and precise self-assemblies of 3D supramolecular structures is of utmost interest. Introducing the concept of self-coordination ligands, herein the design and synthesis of two meta-modified terpyridyl ligands with selective self-complementary coordination moiety are reported and their capability to assemble into two hourglass-shaped nanocages SA and SB is demonstrated. Within these 3D structures, the meta-modified terpyridyl unit preferably coordinates with itself to serve as concave part. By changing the arm length of the ligands, hexamer (SA) and tetramer (SB) are obtained respectively. In-depth studies on the assembly mechanism of SA and SB indicate that the dimers could be formed first via self-complementary coordination and play crucial roles in controlling the final structures. Moreover, both SA and SB can go through hierarchical self-assemblies in solution as well as on solid-liquid interface, which are characterized by transmission electron microscope (TEM) and scanning tunneling microscopy (STM). It is further demonstrated that various higher-order assembly structures can be achieved by tuning the environmental conditions.

Principles of early human development and germ cell program from conserved model systems.

Human primordial germ cells (hPGCs), the precursors of sperm and eggs, originate during weeks 2-3 of early post-implantation development. Using in vitro models of hPGC induction, recent studies have suggested that there are marked mechanistic differences in the specification of human and mouse PGCs. This may be due in part to the divergence in their pluripotency networks and early post-implantation development. As early human embryos are not accessible for direct study, we considered alternatives including porcine embryos that, as in humans, develop as bilaminar embryonic discs. Here we show that porcine PGCs originate from the posterior pre-primitive-streak competent epiblast by sequential upregulation of SOX17 and BLIMP1 in response to WNT and BMP signalling. We use this model together with human and monkey in vitro models simulating peri-gastrulation development to show the conserved principles of epiblast development for competency for primordial germ cell fate. This process is followed by initiation of the epigenetic program and regulated by a balanced SOX17-BLIMP1 gene dosage. Our combinatorial approach using human, porcine and monkey in vivo and in vitro models provides synthetic insights into early human development.

Vibrio cholerae was found in cultured bullfrog.

Bullfrog is one of the most important economic aquatic animals in China that is widely cultured in southern China and is a key breed recommended as an industry of poverty alleviation in China. During recent years, a fatal bacterial disease has often been found in cultured bullfrogs. The clinical manifestations of the diseased bullfrogs were severe intestinal inflammation and an anal prolapse. A bacterial pathogen was isolated from the diseased bullfrog intestines. The bacterium was identified as Vibrio cholerae using morphological, biochemical and 16S rRNA phylogenetic analysis. In this study, V. cholerae was isolated and identified in diseased bullfrogs for the first time, providing a basis for the diagnosis and control of the disease. Therefore, attention should be paid to the modes of transmission of V. cholerae from bullfrog and formulate reasonable safety measures.

Pharmacokinetics studies of eugenol in Pacific white shrimp (Litopenaeus vannamei) after immersion bath.

BACKGROUND: Eugenol is the most commonly used plant anesthetic to relieve the stressors during various aquaculture procedures. This study aims to investigate the pharmacokinetics of eugenol in Pacific white shrimp by immersion baths in a simulated transportation. RESULTS: The pharmacokinetics of eugenol were firstly investigated in Pacific white shrimp by immersion baths of 300 mg L- 1 eugenol over 5 min (Treatment 1), 10 mg L- 1 eugenol during 24 h (Treatment 2) and a sequential immersion administration (Treatment 3). Concentrations of eugenol in hemolymph, hepatopancreas, and muscle were determined using Gas chromatography-tandem mass spectrometry (GC-MS/MS). After immersion bath of Treatment 1, the elimination half-life (t1/2z) values are 1.3 h and 11 h for hepatopancreas and muscles, indicating the rapid absorption and elimination of eugenol in shrimp. Under the Treatment 2 administration, the eugenol peak concentration is 6527.9 µg/kg in muscle, followed by 402.8 µg/kg in hepatopancreas, with the lowest concentration of 37.9 µg/L in hemolymph. Area under the curve (AUC0-∞) values lie in the order of muscle > hepatopancreas > hemolymph, suggesting that eugenol tends to accumulate in muscle by the immersion administration. Moreover, the average residence time (MRT0-∞) values of 38.6, 23.0 and 115.3 h for hemolymph, hepatopancreas and muscle are achieved, which may indicate that hepatopancreas is the main organ for elimination of eugenol. After combining the conditions in a sequential bath immersion of eugenol (Treatment 3), the maximum concentration (Cmax) values of eugenol are higher than those achieved in Treatment 2, indicating that accumulation of eugenol happened in haemolymph, hepatopancreas and muscle. In addition, the corresponding t1/2z values are 4.7, 14.9 and 47.6 h, respectively, suggesting the faster elimination from the tissues following sequential administration. After the immersion bath, eugenol concentrations in muscle of Pacific white shrimp are lower than 2.5 mg/kg at 2 h, 48 h and 24.5 h in Treatment 1 ~ 3. CONCLUSIONS: A withdrawal period of 2 h, 48 h and 24.5 h following a 300 mg L- 1 of eugenol over a 5-min, 10 mg L- 1 eugenol concentration during a 24-h and combined conditions in a sequential immersion bath were suggested.

Dupilumab Provides Rapid and Sustained Improvement in SCORing Atopic Dermatitis Outcomes in Paediatric Patients with Atopic Dermatitis.

This post hoc analysis examined SCORing Atopic Dermatitis (SCORAD) outcomes in 471 paediatric patients (children age 6-<12 years, n = 304; adolescents age 12-<18 years, n = 167) with atopic dermatitis treated with dupilumab, ± topical corticosteroids, in two 16-week phase 3 randomized controlled trials and a 1-year interim data cut of a subsequent open-label extension study. Paediatric patients treated with dupilumab (± topical corticosteroids) had significantly lower SCORAD, objective SCORAD (o-SCORAD), and individual SCORAD components from week 3 to 16 compared with placebo (± topical corticosteroids) in the randomized controlled trials. The results were sustained or continuously improved over 1 year of open-label treatment with dupilumab ± topical corticosteroids. SCORAD-50 was achieved in almost all patients (91.3-91.8%) by week 52 with continued dupilumab treatment across age groups. Almost all (> 86%) patients achieved mild or absent pruritus and sleep loss at week 52. In conclusion, dupilumab ± topical corticosteroids resulted in rapid and significant improvements in all aspects of SCORAD analysed, and the results were sustained over 1 year.

Identification of CDPK Gene Family in Solanum habrochaites and Its Function Analysis under Stress.

Tomato is an important vegetable crop. In the process of tomato production, it will encounter abiotic stress, such as low temperature, drought, and high salt, and biotic stress, such as pathogen infection, which will seriously affect the yield of tomato. Calcium-dependent protein kinase (CDPK) is a class of major calcium signal receptor which has an important regulatory effect on the perception and decoding of calcium signals. CDPK plays a key role in many aspects of plant growth, such as the elongation of pollen tubes, plant growth, and response to biotic and abiotic stress. While some studies have concentrated on Arabidopsis and pepper, Solanum habrochaites is a wild species relative of cultivated tomato and there is no report on CDPK in Solanum habrochaites to date. Using tomato genomic data, this study identified 33 members of the CDPK gene family. Evolutionary analysis divides family members into four Asian groups, of which the CDPK family members have 11 gene replication pairs. Subcellular location analysis showed that most proteins were predicted to be located in the cytoplasm, and less protein existed on the cell membrane. Not all CDPK family members have a transmembrane domain. Cis regulatory elements relating to light, hormones, and drought stress are overrepresented in the promoter region of the CDPK genes in Solanum habrochaites. The expression levels of each gene under biotic stress and abiotic stress were quantified by qRT-PCR. The results showed that members of the CDPK family in Solanum habrochaites respond to different biotic and abiotic stresses. Among them, the expression of ShCDPK6 and ShCDPK26 genes change significantly. ShCDPK6 and ShCDPK26 genes were silenced using VIGS (virus-induced gene silencing), and the silenced plants illustrated reduced stress resistance to Botrytis cinerea, cold, and drought stress. The results of this study will provide a basis for the in-depth study of the CDPK gene family in Solanum habrochaites, laying the foundation for further analysis of the function of the gene family.

New 11-Methoxymethylgermacranolides from the Whole Plant of Carpesium divaricatum.

Eight new 11-methoxymethylgermacranolides (1-8) were isolated from the ethanol extract of the whole plant of Carpesium divaricatum. The planar structures and relative configurations of the new compounds were determined by detailed spectroscopic analysis. The absolute configuration of 1 was established by electronic circular dichroism (ECD) spectrum and X-ray crystallographic analysis, and the stereochemistry of the new compounds 2-8 were determined by similar ECD data with 1. The absolute configurations of 5 and 7 were further confirmed by using quantum chemical electronic circular dichroism (ECD) calculations. Compound 4 exhibited weak cytotoxicity against MCF-7 cells. Compound 8 could potently decrease PGE2 productions in LPS-induced RAW 264.7 cells.

Real-world persistence with dupilumab among adults with atopic dermatitis.

BACKGROUND: The real-world persistence with dupilumab therapy for atopic dermatitis (AD) is unknown. OBJECTIVE: To characterize adults with AD who initiated dupilumab and evaluate persistence with dupilumab therapy. METHODS: This retrospective cohort study used the IBM MarketScan Commercial and Medicare database. Adults with AD who initiated dupilumab (first dispensation = index date) between March 28, 2017, and March 31, 2018, were identified and followed up until September 30, 2018, or disenrollment. Twelve months of continuous preindex enrollment were required to characterize baseline treatment history and comorbidities. Kaplan-Meier analysis was used to estimate dupilumab persistence at 6 and 12 months, assuming a 14-day injection frequency and a 30-day grace period. RESULTS: A total of 1963 adults were identified who initiated dupilumab (mean [SD] age 42.1 [15.7] years; 50.7% women; 49.8% with ≥1 atopic comorbidity). Baseline AD treatments included topical corticosteroids (81.6%), systemic corticosteroids (72.5%), and systemic immunosuppressants (22.8%). Dupilumab persistence (95% confidence interval) at 6 and 12 months was 91.9% (90.7%-93.2%) and 77.3% (75.0%-79.7%), respectively. Among 329 patients who discontinued dupilumab, the risk of reinitiation was 78.8% (95% confidence interval: 75.8%-81.7%) within an average of 4 months. CONCLUSION: Dupilumab persistence at 12 months was high, suggesting patient satisfaction with effectiveness, tolerability, and treatment regimen.

One pair of new enantiomeric trinorsesquiterpenes from the aerial parts of Justicia gendarussa.

A pair of new enantiomeric trinorsesquiterpenes, (+)-genpenterpene A (1a) and (-)-genpenterpene A (1b), together with seven known compounds (2-8), were isolated from the aerial parts of Justicia gendarussa Burm.f.. All of these known compounds were isolated from this plant for the first time. Racemic genpenterpene A was separated by chiral HPLC column. Their chemical structures were elucidated based on extensive spectroscopic analysis, single crystal X-ray diffraction, and ECD calculations. (+)-genpenterpene A (1a) exhibited potent inhibitory effect against nitric oxide production in lipopolysaccharide-activated RAW 264.7 mouse macrophage cells with an IC50 value of 9.54 ± 1.02 µM.

Barbaram, a bicyclic neolactam from the root and stem of Lycium barbarum.

Barbaram (1), a neolactam together with other five known compunds (2-6) was isolated from the EtOAc-soluble fraction of an EtOH extract of the root and stem of Lycium barbarum by using silica gel, Sephadex LH-20 column chromatography and semi-preparative RP-C18 HPLC. Based on HR-TOF-MS, NMR spectral data, quantum chemistry ECD calculations and referencing to the data reported earlier, the structures of these compounds (1-6) were determined, specially including the absolute configuration of the neolactam (1). Compounds 2 and 4 showed significant anti-inflammatory activity in LPS-induced RAW 264.7 macrophages with the IC50 values of 8.98 ± 0.57 µM, 6.68 ± 0.77 µM.

Adsorption of REEs from Aqueous Solution by EDTA-Chitosan Modified with Zeolite Imidazole Framework (ZIF-8).

Chitosan (CS) modified with ethylenediamine tetraacetic acid (EDTA) was further modified with the zeolite imidazole framework (ZIF-8) by in situ growth method and was employed as adsorbent for the removal of rare-earth elements (REEs). The material (EDTA-CS@ZIF-8) and ZIF-8 and CS were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), and nitrogen adsorption/desorption experiments (N2- Brunauer-Emmet-Teller (BET)). The effects of adsorbent dosage, temperature, the pH of the aqueous solution, contact time on the adsorption of REEs (La(III), Eu(III), and Yb(III)) by EDTA-CS@ZIF-8 were studied. Typical adsorption isotherms (Langmuir, Freundlich, and Dubinin-Radushkevich (D-R)) were determined for the adsorption process, and the maximal adsorption capacity was estimated as 256.4 mg g-1 for La(III), 270.3 mg g-1 for Eu(III), and 294.1 mg g-1 for Yb(III). The adsorption kinetics results were consistent with the pseudo-second-order equation, indicating that the adsorption process was mainly chemical adsorption. The influence of competing ions on REE adsorption was also investigated. After multiple cycles of adsorption/desorption behavior, EDTA-CS@ZIF-8 still maintained high adsorption capacity for REEs. As a result, EDTA-CS@ZIF-8 possessed good adsorption properties such as stability and reusability, which have potential application in wastewater treatment.

[Chemical constituents from Xanthii Fructus].

This study was carried out to investigate the chemical constituents from Xanthii Fructus(the fruits of Xanthium sibiricum). The compounds were separated and purified by silica gel column chromatography, Sephadex LH-20 and ODS chromatography and semi-preparative HPLC. Base on HR-ESI-MS, NMR and other spectral data, their structures were identified. The anti-inflammatory activity of the isolated compounds was evaluated by lipopolysaccharide(LPS)-induced macrophage RAW264.7 as a screening model. A total of twenty-one compounds were isolated from the EtOAc fraction of 95% ethanol extract and identified as uracil(1), thymine(2), uridine(3), indole-3-carbaldehyde(4), indole-3-carboxylic acid(5), 2'-O-methyluridine(6), guanosine(7), 2,4(1H,3H)-quinazolinedione(8), 3-hydroxy-3-(2-hydroxyethyl)indolin-2-one(9), nicotinamide(10), N-acetyl-L-phenylalaninol(11), heliolactam(12), terresoxazine(13), caudatin(14), qingyangshengenin(15), caudatin-3-O-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-cymaropyranoside(16), caudatin-3-O-ß-D-cymaropyranosyl-(1→4)-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-cymaropyranoside(17), caudatin-3-O-α-L-cymaropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-α-L-cymaropyranosyl-(1→4)-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranoside(18), qinyangshengenin-3-O-ß-D-oleandropyranosyl-(1→4)-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranoside(19), qinyangshengenin-3-O-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-digitoxopyranoside(20), rostratamine-3-O-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-cymaropyranoside(21). Compounds 5-21 are obtained from genus Xanthium for the first time. Compounds 12 and 13 indirectly exhibited anti-inflammatory activity by suppressing LPS-induced NO production in RAW264.7 cells with IC_(50) values of(15.45±0.56) and(20.14±0.78) µmol·L~(-1), respectively.

The NF-κB-modulated microRNAs miR-195 and miR-497 inhibit myoblast proliferation by targeting Igf1r, Insr and cyclin genes.

MicroRNAs (miRNAs) play important roles in the development of skeletal muscle. In our previous study, expression of miR-195 and miR-497 were shown to be upregulated during muscle development in pigs. In this study, we investigated the roles of these two miRNAs in myogenesis and analyzed their transcriptional regulation. Our results showed that miR-195 and miR-497 were upregulated during muscle development and myoblast differentiation. Moreover, miR-195 and miR-497 inhibited proliferation but not differentiation in C2C12 cells. Further investigation revealed that Igf1r, Insr, Ccnd2 and Ccne1 were directly targeted by miR-195 and miR-497 in myoblasts. In addition, we confirmed that miR-195 and miR-497, which shared the similar expression profiling, were negatively regulated by nuclear factor κB (NF-κB) in both myoblasts and skeletal muscle tissue. Our data illustrate that the signaling pathway NF-κB-miR-195/497-Igf1r/Insr-Ccnd2/Ccne1 plays important roles in myogenesis. Our study provides novel evidence for the roles of miR-195 and miR-497 in muscle development.

Paracrine effects of embryo-derived FGF4 and BMP4 during pig trophoblast elongation.

The crosstalk between the epiblast and the trophoblast is critical in supporting the early stages of conceptus development. FGF4 and BMP4 are inductive signals that participate in the communication between the epiblast and the extraembryonic ectoderm (ExE) of the developing mouse embryo. Importantly, however, it is unknown whether a similar crosstalk operates in species that lack a discernible ExE and develop a mammotypical embryonic disc (ED). Here we investigated the crosstalk between the epiblast and the trophectoderm (TE) during pig embryo elongation. FGF4 ligand and FGFR2 were detected primarily on the plasma membrane of TE cells of peri-elongation embryos. The binding of this growth factor to its receptor triggered a signal transduction response evidenced by an increase in phosphorylated MAPK/ERK. Particular enrichment was detected in the periphery of the ED in early ovoid embryos, indicating that active FGF signalling was operating during this stage. Gene expression analysis shows that CDX2 and ELF5, two genes expressed in the mouse ExE, are only co-expressed in the Rauber's layer, but not in the pig mural TE. Interestingly, these genes were detected in the nascent mesoderm of early gastrulating embryos. Analysis of BMP4 expression by in situ hybridisation shows that this growth factor is produced by nascent mesoderm cells. A functional test in differentiating epiblast shows that CDX2 and ELF5 are activated in response to BMP4. Furthermore, the effects of BMP4 were also demonstrated in the neighbouring TE cells, as demonstrated by an increase in phosphorylated SMAD1/5/8. These results show that BMP4 produced in the extraembryonic mesoderm is directly influencing the SMAD response in the TE of elongating embryos. These results demonstrate that paracrine signals from the embryo, represented by FGF4 and BMP4, induce a response in the TE prior to the extensive elongation. The study also confirms that expression of CDX2 and ELF5 is not conserved in the mural TE, indicating that although the signals that coordinate conceptus growth are similar between rodents and pigs, the gene regulatory network of the trophoblast lineage is not conserved in these species.

Recalcitrant vulnerability curves: methods of analysis and the concept of fibre bridges for enhanced cavitation resistance.

Vulnerability curves (VCs) generally can be fitted to the Weibull equation; however, a growing number of VCs appear to be recalcitrant, that is, deviate from a Weibull but seem to fit dual Weibull curves. We hypothesize that dual Weibull curves in Hippophae rhamnoides L. are due to different vessel diameter classes, inter-vessel hydraulic connections or vessels versus fibre tracheids. We used dye staining techniques, hydraulic measurements and quantitative anatomy measurements to test these hypotheses. The fibres contribute 1.3% of the total stem conductivity, which eliminates the hypothesis that fibre tracheids account for the second Weibull curve. Nevertheless, the staining pattern of vessels and fibre tracheids suggested that fibres might function as a hydraulic bridge between adjacent vessels. We also argue that fibre bridges are safer than vessel-to-vessel pits and put forward the concept as a new paradigm. Hence, we tentatively propose that the first Weibull curve may be accounted by vessels connected to each other directly by pit fields, while the second Weibull curve is associated with vessels that are connected almost exclusively by fibre bridges. Further research is needed to test the concept of fibre bridge safety in species that have recalcitrant or normal Weibull curves.