Decoding the enigmatic estrogen paradox in pulmonary hypertension: delving into estrogen metabolites and metabolic enzymes.

Pulmonary hypertension (PH) presents a puzzling sex bias, being more prevalent in women yet often less severe than in men, and the underlying reasons remain unclear. Studies using animal models, and limited clinical data have revealed a protective influence of exogenous estrogens, known as the estrogen paradox. Research suggests that beyond its receptor-mediated effects, estrogen acts through metabolites such as 2-ME2, 4-OHE2, and 16-OHE2, which are capable of exhibiting protective or detrimental effects in PH, prompting the need to explore their roles in PH to untangle sex differences and the estrogen paradox.

The changes in sugar content and the selection of key genes at different developmental stages of 'Katy' and 'Kuijin' apricots.

'Katy' and 'Kuijin' apricots are the main cultivated varieties in Shandong province. The flavor of the fruit is mainly determined by sugars and acids, with soluble sugar components serving as important nutritional elements in fruits as well as crucial indicators of fruit sweetness and flavor quality. However, little is known about the changes in soluble sugar content, especially sucrose content, and the sucrose metabolism mechanism during the entire fruit growth and development process of 'Katy' and 'Kuijin' apricots.

Recent Advances in the Linkers of Drug Conjugates.

Drug conjugates have emerged as a pivotal research focus in the field of targeted cancer therapy. They represent a widely explored prodrug strategy that significantly enhances the therapeutic index of drugs while minimizing side effects. The stability and selective cleavage of the linker within drug conjugates are critical for the therapeutic efficacy and targeted treatment achieved by these conjugates.

Transcriptome analysis and functional study of phospholipase A in Galleria mellonella larvae lipid metabolism in response to envenomation by an ectoparasitoid, Iseropus kuwanae.

There is abundant evidence that parasitoids manipulate their hosts by envenomation to support the development and survival of their progeny before oviposition. However, the specific mechanism underlying host nutritional manipulation remains largely unclear. To gain a more comprehensive insight into the effects induced by the gregarious ectoparasitoid Iseropus kuwanae (Hymenoptera: Ichneumonidae) on the greater wax moth Galleria mellonella (Lepidoptera: Pyralidae) larvae, we sequenced the transcriptome of both non-envenomed and envenomed G.

COG-imposed Golgi functional integrity determines the onset of dark-induced senescence.

Plant survival depends on dynamic stress-response pathways in changing environments. To uncover pathway components, we screened an ethyl methanesulfonate-mutagenized transgenic line containing a stress-inducible luciferase construct and isolated a constitutive expression mutant. The mutant is the result of an amino acid substitution in the seventh subunit of the hetero-octameric conserved oligomeric Golgi (COG) complex of Arabidopsis thaliana.

Revealing the extracellular function of HMGB1 N-terminal region acetylation assisted by a protein semi-synthesis approach.

HMGB1 (high-mobility group box 1) is a non-histone chromatin-associated protein that has been widely reported as a representative damage-associated molecular pattern (DAMP) and to play a pivotal role in the proinflammatory process once it is in an extracellular location. Accumulating evidence has shown that HMGB1 undergoes extensive post-translational modifications (PTMs) that actively regulate its conformation, localization, and intermolecular interactions. However, fully characterizing the functional implications of these PTMs has been challenging due to the difficulty in accessing homogeneous HMGB1 with site-specific PTMs of interest.

Transcriptome and metabolome analysis of flavonol synthesis in apricot fruits.

Introduction: Apricot fruits are edible and serve as a source of medicinal compounds. Flavonols are important plant secondary metabolites that have antioxidant and antitumor effects and may promote cardiovascular health.

Methods: The flavonoid content in three stages of the 'Kuijin' and the 'Katy' was observed, followed by the combination of metabolome and transcriptome analysis to explore the metabolic basis of flavonol synthesis.

Inhibitory effect and underlying mechanism of cinnamon and clove essential oils on and causing rots in postharvest bagging-free apple fruits.

Bagging-free apple is more vulnerable to postharvest disease, which severely limits the cultivation pattern transformation of the apple industry in China. This study aimed to ascertain the dominant pathogens in postharvest bagging-free apples, to evaluate the efficacy of essential oil (EO) on inhibition of fungal growth, and to further clarify the molecular mechanism of this action. By morphological characteristics and rDNA sequence analyses, () and () were identified as the main pathogens isolated from decayed bagging-free apples.

Molecular mechanism of Wilms' tumor (Wt1) (+/-KTS) variants promoting proliferation and migration of ovarian epithelial cells by bioinformatics analysis.

Epithelial ovarian cancer (EOC) is a gynecological disease with the highest mortality. With the lack of understanding of its pathogenesis, no accurate early diagnosis and screening method has been established for EOC. Studies revealed the multi-faceted function of Wilms' tumor (Wt1) genes in cancer, which may be related to the existence of multiple alternative splices.

Residual levels and dietary intake risk assessment of 11 pesticides in apricots from different ecological planting regions in China.

The frequent and massive use of pesticides has led to pesticide residues in apricot, threatening food safety and human health. A reliable and simple modified QuEChERS method with ultra-performance liquid chromatography-tandem mass spectrometry was developed for the simultaneous determination of 11 pesticides in apricot. Method validation indicated that satisfied linearity (R ≥ 0.

Clarifying the mechanisms of the light-induced color formation of apple peel under dark conditions through metabolomics and transcriptomic analyses.

Many studies have demonstrated that anthocyanin synthesis in apple peel is induced by light, but the color of bagged apple peel continues to change under dark conditions after light induction has not been characterized. Here, transcriptional and metabolic changes associated with changes in apple peel coloration in the dark after different light induction treatments were studied. Apple pericarp can achieve a normal color under complete darkness followed by light induction.

TEB/POLQ plays dual roles in protecting Arabidopsis from NO-induced DNA damage.

Nitric oxide (NO) is a key player in numerous physiological processes. Excessive NO induces DNA damage, but how plants respond to this damage remains unclear. We screened and identified an Arabidopsis NO hypersensitive mutant and found it to be allelic to TEBICHI/POLQ, encoding DNA polymerase θ.

Reciprocity between a retrograde signal and a putative metalloprotease reconfigures plastidial metabolic and structural states.

Reconfiguration of the plastidial proteome in response to environmental cues is central to tailoring adaptive responses. To define the underlying mechanisms and consequences of these reconfigurations, we performed a suppressor screen, using a mutant () accumulating high levels of a plastidial retrograde signaling metabolite, MEcPP. We isolated a revertant partially suppressing the dwarf stature and high salicylic acid of and identified the mutation in a putative plastidial metalloprotease (VIR3).

ADH2/GSNOR1 is a key player in limiting genotoxic damage mediated by formaldehyde and UV-B in Arabidopsis.

Maintenance of genome stability is an essential requirement for all living organisms. Formaldehyde and UV-B irradiation cause DNA damage and affect genome stability, growth and development, but the interplay between these two genotoxic factors is poorly understood in plants. We show that Arabidopsis adh2/gsnor1 mutant, which lacks alcohol dehydrogenase 2/S-nitrosoglutathione reductase 1 (ADH2/GSNOR1), are hypersensitive to low fluence UV-B irradiation or UV-B irradiation-mimetic chemicals.

Correction: Nutritional targeting modification of silkworm pupae oil catalyzed by a smart hydrogel immobilized lipase.

Correction for 'Nutritional targeting modification of silkworm pupae oil catalyzed by a smart hydrogel immobilized lipase' by Jin-Zheng Wang , , 2021, , 6240-6253, DOI: 10.1039/D1FO00913C.

A plastidial retrograde signal potentiates biosynthesis of systemic stress response activators.

Plants employ an array of intricate and hierarchical signaling cascades to perceive and transduce informational cues to synchronize and tailor adaptive responses. Systemic stress response (SSR) is a recognized complex signaling and response network quintessential to plant's local and distal responses to environmental triggers; however, the identity of the initiating signals has remained fragmented. Here, we show that both biotic (aphids and viral pathogens) and abiotic (high light and wounding) stresses induce accumulation of the plastidial-retrograde-signaling metabolite methylerythritol cyclodiphosphate (MEcPP), leading to reduction of the phytohormone auxin and the subsequent decreased expression of the phosphatase PP2C.

Complex cyclic peptide synthesis via serine/threonine ligation chemistry.

Non-ribosomal cyclic peptides are abundant in natural sources, exhibiting attractive bioactivities and favorable pharmacological properties. Furthermore, their structural complexity renders them as attractive synthetic targets. A general task for cyclic peptide synthesis is the peptide cyclization.

Chiral Phosphoric Acid Catalyzed Asymmetric Desymmetrization of -Quinamines with Isocyanates: Access to Functionalized Imidazolidin-2-one Derivatives.

The development of enantioselective desymmetrization of -quinamines with isocyanates catalyzed by chiral phosphoric acid is reported. The strategy provides concise access to functionalized imidazolidin-2-one derivatives in high yields and enantioselectivities under mild reaction conditions. Remarkably, this reaction could be performed on a gram scale using 5 mol % catalyst loading and the chiral imidazolidin-2-one derivatives could be easily transformed into valuable scaffolds without disturbing the enantiopurity, demonstrating the synthetic utility of this protocol.

Discovery of Novel Small Molecule Inhibitors Disrupting the PCSK9-LDLR Interaction.

Proprotein convertase subtilisin kexin 9 (PCSK9) has been identified as a reliable therapeutic target for hypercholesterolemia and coronary artery heart diseases since the monoclonal antibodies of PCSK9 have launched. Disrupting the protein-protein interaction (PPI) between PCSK9 and the low-density lipoprotein receptor (LDLR) has been considered as a promising approach for developing PCSK9 inhibitors. However, PPIs have been traditionally considered difficult to target by small molecules since the PPI surface is usually large, flat, featureless, and without a "pocket" or "groove" for ligand binding.

Nighttime Temperatures and Sunlight Intensities Interact to Influence Anthocyanin Biosynthesis and Photooxidative Sunburn in "Fuji" Apple.

Light and low temperatures induce anthocyanin accumulation, but intense sunlight causes photooxidative sunburn. Nonetheless, there have been few studies of anthocyanin synthesis under different sunlight intensities and low nighttime temperatures. Here, low nighttime temperatures followed by low light intensity were associated with greater anthocyanin accumulation and the expression of anthocyanin biosynthesis genes in "Fuji" apple peel.

Total Synthesis of Mannopeptimycin β via β-Hydroxyenduracididine Ligation.

Nonribosomal peptide synthesis in bacteria has endowed cyclic peptides with fascinating structural complexity via incorporating nonproteinogenic amino acids. These bioactive cyclic peptides provide interesting structural motifs for exploring total synthesis and medicinal chemistry studies. Cyclic glycopeptide mannopeptimycins exhibit antibacterial activity against antibiotic-resistant Gram-positive pathogens and act as the lipid II binder to stop bacterial cell wall biosynthesis.