Isostructural doping for organic persistent mechanoluminescence.

Mechanoluminescence, featuring light emission triggered by mechanical stimuli, holds immense promise for diverse applications. However, most organic Mechanoluminescence materials suffer from short-lived luminescence, limiting their practical applications. Herein, we report isostructural doping as a valuable strategy to address this challenge. By strategically modifying the host matrices with specific functional groups and simultaneously engineering guest molecules with structurally analogous features for isostructural doping, we have successfully achieved diverse multicolor and high-efficiency persistent mechanoluminescence materials with ultralong lifetimes. The underlying persistent mechanoluminescence mechanism and the universality of the isostructural doping strategy are also clearly elucidated and verified. Moreover, stress sensing devices are fabricated to show their promising prospects in high-resolution optical storage, pressure-sensitive displays, and stress monitoring. This work may facilitate the development of highly efficient organic persistent mechanoluminescence materials, expanding the horizons of next-generation smart luminescent technologies.

The relationship between circulating metabolites and prostate hyperplasia: a Mendelian randomization study.

BACKGROUND: Circulating metabolites (CM) play a pivotal role in our overall health, yet the current evidence concerning the involvement of diverse CM in benign prostatic hyperplasia (BPH) remains limited. Mendelian randomization (MR) offers a promising avenue to explore the potential impact of CM on BPH. METHODS: In a forward MR analysis, a cohort of 249 circulating metabolites was employed as exposures to investigate their potential associations with BPH risk. Conversely, in a reverse MR analysis, BPH was employed as an exposure to assess its effects on CM. RESULTS: The forward MR analysis discerned a linkage between six metabolites and BPH, with careful consideration to excluding heterogeneity and pleiotropy. Subsequently, the reverse MR analysis unveiled that nine metabolic compounds, mainly comprising phospholipids and triglycerides, potentially exhibit elevated levels in BPH patients. CONCLUSION: Bidirectional MR analysis furnishes genetic insight into the interplay between CM and BPH. The prominence of lipids and triglycerides emerges as significant factors intricately linked to BPH risk.

A Rigid Multiple Resonance Thermally Activated Delayed Fluorescence Core Toward Stable Electroluminescence and Lasing.

The investigation of organic light-emitting diodes (OLEDs) and organic laser devices with thermally activated delayed fluorescence (TADF) molecules is emerging due to the potential of harnessing triplets. In this work, a boron/nitrogen multiple-resonance TADF polycyclic framework fusing carbazole units (CzBNPh) was proposed. CzBNPh exhibited a narrowband emission (<30 nm), a unity photoluminescence quantum yield, and a fast radiative rate. Consequently, CzBNPh demonstrated a low distributed feedback (DFB) lasing threshold of 0.68 µJ cm-2 . Furthermore, the stimulated emission zone of CzBNPh was effectively separated from its singlet and triplet absorption, thereby minimizing the singlet-triplet annihilation under long-pulsed excitation ranging from 20 µs to 2.5 ms. Significantly, the enhanced rigid molecular conformation, thermal stability, and photo-stability resulted in improved lasing and electroluminescence stability compared to that of 5,9-diphenyl-5,9-diaza-13b-boranaphtho[3,2,1-de]anthracene (DABNA)-core. These findings indicate the potential of CzBN-core as a promising framework for achieving long-pulsed wave and electrically-pumped lasing in the future.

Oxygen-Tolerant Near-Infrared Organic Long-Persistent Luminescent Copolymers.

Organic materials exhibiting long-lasting emission in the near infrared are expected to have applications in bio-imaging and other areas. Although room temperature phosphorescence and thermally activated delayed fluorescence display long-lived emission of approximately one minute, organic long-persistent luminescence (OLPL) systems with a similar emission mechanism to inorganic persistent emitters can emit for several hours at room temperature. In particular OLPL with a hole-diffusion mechanism can function even in the presence of oxygen. However, ionic materials lack long-term stability in neutral organic host owing to aggregation and phase separation. In this study, we synthesized polymers with stable near-infrared persistent luminescence at room temperature via the copolymerization of electron donors and acceptors. The copolymers exhibit long-persistent luminescence (LPL) at temperatures below the glass transition temperature and can be excited by approximately the entire range of visible light. LPL properties and spectra can be controlled by the dopant.

Synthesis of a π-Extended Double [9]Helicene.

Double helicenes are appealing chiral frameworks. Their π-extension is desirable to achieve (chir)optical response in the visible and near-infrared (NIR) region, but access to higher double [n]helicenes (n≥8) has remained challenging. Herein, we report an unprecedented π-extended double [9]helicene (D9H), unambiguously revealing its structure by single-crystal X-ray diffraction. D9H shows remarkable NIR emission from 750 to 1100 nm with a high photoluminescence quantum yield of 18 %. In addition, optically pure D9H exhibits panchromatic circular dichroism with a notable dissymmetry factor (gCD ) of 0.019 at 590 nm, which is among the highest in the visible region for reported helicenes.

Based on network pharmacology and molecular docking to predict the mechanism of Huangqi in the treatment of castration-resistant prostate cancer.

BACKGROUND: As a kind of traditional Chinese medicine, HQ is widely mentioned in the treatment of cancerous diseases in China, which has been proven to have a therapeutic effect on cancerous diseases, such as prostate cancer. To predict the specific mechanism of HQ in the treatment of CRPC, we will conduct preliminary verification and discussion based on a comprehensive consideration of network pharmacology and molecular docking. METHODS: TCMSP was used to obtain the compounds and reach the effective targets of HQ. The targets of CRPC were reached based on GeneCards database and CTD database. GO and KEGG were utilized for the analysis of overlapping targets. The software of Openbabel was used to convert the formats of ligands and reporters. In addition, molecular docking studies were performed by using the software of Autodock Vina. RESULT: It can be seen from the database results that there were 87 active compounds (20 key active compounds) in HQ, and 33 targets were screened out for CRPC treatment. GO and KEGG pathway enrichment analyses identified 81 significant GO terms and 24 significant KEGG pathways. There is a difference in terms of the expression of core protein between cancer patients and healthy people. The expression of core protein in patients also has an impact on the life cycle. The results of molecular docking showed that the docking activity of drug molecules and core proteins was better. CONCLUSIONS: It is concluded from the results of this network pharmacology and molecular docking that HQ makes a multi-target and multi-biological process, and results in the multi-channel synergistic effect on the treatment of CRPC by regulating cell apoptosis, proliferation and metastasis, which still needs further verification by experimental research.

Evidence for quasar fast outflows being accelerated at the scale of tens of parsecs.

Quasar outflows may play a crucial role in regulating the host galaxy, although the spatial scale of quasar outflows remain a major enigma, with their acceleration mechanism poorly understood. The kinematic information of outflow is the key to understanding its origin and acceleration mechanism. Here, we report the galactocentric distances of different outflow components for both a sample and an individual quasar. We find that the outflow distance increases with velocity, with a typical value from several parsecs to more than one hundred parsecs, providing direct evidence for an acceleration happening at a scale of the order of 10 parsecs. These outflows carry ∼1% of the total quasar energy, while their kinematics are consistent with a dust-driven model with a launching radius comparable to the scale of a dusty torus, indicating that the coupling between dust and quasar radiation may produce powerful feedback that is crucial to galaxy evolution.

Organic long-persistent luminescence stimulated by visible light in p-type systems based on organic photoredox catalyst dopants.

Organic long-persistent-luminescent (OLPL) materials demonstrating hour-long photoluminescence have practical advantages in applications owing to their flexible design and easy processability. However, the energy absorbed in these materials is typically stored in an intermediate charge-separated state that is unstable when exposed to oxygen, thus preventing persistent luminescence in air unless oxygen penetration is suppressed through crystallization. Moreover, OLPL materials usually require ultraviolet excitation. Here we overcome such limitations and demonstrate amorphous OLPL systems that can be excited by radiation up to 600 nm and exhibit persistent luminescence in air. By adding cationic photoredox catalysts as electron-accepting dopants in a neutral electron-donor host, stable charge-separated states are generated by hole diffusion in these blends. Furthermore, the addition of hole-trapping molecules extends the photoluminescence lifetime. By using a p-type host less reactive to oxygen and tuning the donor-acceptor energy gap, our amorphous blends exhibit persistent luminescence stimulated by visible light even in air, expanding the applicability of OLPL materials.

SEC23A rescues SEC23B-deficient congenital dyserythropoietic anemia type II.

Congenital dyserythropoietic anemia type II (CDAII) results from loss-of-function mutations in SEC23B. In contrast to humans, SEC23B-deficient mice deletion do not exhibit CDAII but die perinatally with pancreatic degeneration. Here, we demonstrate that expression of the full SEC23A protein (the SEC23B paralog) from the endogenous regulatory elements of Sec23b completely rescues the SEC23B-deficient mouse phenotype. Consistent with these data, while mice with erythroid-specific deletion of either Sec23a or Sec23b do not exhibit CDAII, we now show that mice with erythroid-specific deletion of all four Sec23 alleles die in mid-embryogenesis with features of CDAII and that mice with deletion of three Sec23 alleles exhibit a milder erythroid defect. To test whether the functional overlap between the SEC23 paralogs is conserved in human erythroid cells, we generated SEC23B-deficient HUDEP-2 cells. Upon differentiation, these cells exhibited features of CDAII, which were rescued by increased expression of SEC23A, suggesting a novel therapeutic strategy for CDAII.

Epidemiologic and Genetic Associations of Erythropoietin With Blood Pressure, Hypertension, and Coronary Artery Disease.

[Figure: see text].

[Impacts of the expressions of Fas and FasL mRNA and proteins on sperm concentration and motility].

Objective: To investigate the influence of the expressions of apoptosis-related Fas and FasL mRNA and proteins on sperm concentration and motility. METHODS: We collected semen samples from 80 adult males and divided them into four groups of an equal number according to sperm concentration and the percentage of progressively motile sperm (PMS): normal, asthenospermia (AS), oligozoospermia (OS) and oligoasthenospermia (OAS). We examined the routine semen parameters, the levels of Fas and FasL proteins and the expressions of Fas and FasL genes in different groups. RESULTS: The sperm concentrations in the normal, AS, OS and OAS groups were (68.11 ± 35.49), (92.21 ± 60.96), (8.55 ± 2.82) and (5.96 ± 3.80) ×106/ml, respectively, and the percentages of PMS were (49.40 ± 13.86)%, (22.12 ± 7.13)%, (40.77 ± 8.41)% and (14.53 ± 9.74), respectively. The Fas protein level was significantly higher in the AS, OS and OAS than in the normal group (ï¼»425.03 ± 50.56ï¼½, ï¼»442.32 ± 84.88ï¼½ and ï¼»448.42 ± 84.79ï¼½ vs ï¼»381.07 ± 52.37ï¼½ pg/ml, P < 0.05), correlated negatively with sperm concentration (r = －0.377, P < 0.01) and PMS (r = －0.350, P < 0.01), but exhibited no statistically significant differences between the former three and latter group (ï¼»166.98 ± 27.39ï¼½, ï¼»169.51 ± 32.62ï¼½ and ï¼»171.46 ± 32.61ï¼½ vs ï¼»167.49 ± 29.91ï¼½ pg/ml, P > 0.05). The relative levels of the Fas gene in the normal, AS, OS and OAS groups were 1, (0.88 ± 1.17), (2.55 ± 2.11) and (0.69 ± 0.90) respectively, lower in the AS and OAS than in the normal group, and positively correlated with sperm motility; those of the FasL gene were 1, (1.99 ± 1.81), (2.08 ± 2.06) and (2.03 ± 2.23) respectively, higher in the OS and OAS than in the normal group, and negatively correlated with sperm motility. Compared with the normal group, the expressions of Fas and FasL were down-regulated in the AS but up-regulated in the OS group; the expression of Fas, however, was down-regulated and that of FasL up-regulated in the OAS group. The expression of Fas mRNA was positively correlated with the percentage of PMS (r = 0.355, P = 0.01) and total sperm motility (r = 0.358, P < 0.01), while sperm concentration negatively correlated with the expression FasL mRNA (r = －0.305, P < 0.05). There was no significant correlation between the other parameters. CONCLUSIONS: Fas and FasL are differentially expressed in normal, asthenospermia, oligozoospermia and oligoasthenospermia males. Their up-regulated expressions may promote the apoptosis of spermatogenic and sperm cells and induce oligozoospermia, while their down-regulated expressions may indicate the failure of abnormal spermatogenic and sperm cells to immediately undergo programmed death, which can be one of the causes of asthenospermia.

The Endoplasmic Reticulum Cargo Receptor SURF4 Facilitates Efficient Erythropoietin Secretion.

Erythropoietin (EPO) stimulates erythroid differentiation and maturation. Though the transcriptional regulation of EPO has been well studied, the molecular determinants of EPO secretion remain unknown. Here, we generated a HEK293T reporter cell line that provides a quantifiable and selectable readout of intracellular EPO levels and performed a genome-scale CRISPR screen that identified SURF4 as an important mediator of EPO secretion. Targeting SURF4 with multiple independent single guide RNAs (sgRNAs) resulted in intracellular accumulation and extracellular depletion of EPO. Both of these phenotypes were rescued by expression of SURF4 cDNA. Additionally, we found that disruption of SURF4 resulted in accumulation of EPO in the endoplasmic reticulum (ER) compartment and that SURF4 and EPO physically interact. Furthermore, SURF4 disruption in Hep3B cells also caused a defect in the secretion of endogenous EPO under conditions mimicking hypoxia, ruling out an artifact of heterologous overexpression. This work demonstrates that SURF4 functions as an ER cargo receptor that mediates the efficient secretion of EPO. Our findings also suggest that modulating SURF4 may be an effective treatment for disorders of erythropoiesis that are driven by aberrant EPO levels. Finally, we show that SURF4 overexpression results in increased secretion of EPO, suggesting a new strategy for more efficient production of recombinant EPO.

Influence of energy gap between charge-transfer and locally excited states on organic long persistence luminescence.

Organic long-persistent luminescence (LPL) is an organic luminescence system that slowly releases stored exciton energy as light. Organic LPL materials have several advantages over inorganic LPL materials in terms of functionality, flexibility, transparency, and solution-processability. However, the molecular selection strategies for the organic LPL system still remain unclear. Here we report that the energy gap between the lowest localized triplet excited state and the lowest singlet charge-transfer excited state in the exciplex system significantly controls the LPL performance. Changes in the LPL duration and spectra properties are systematically investigated for three donor materials having a different energy gap. When the energy level of the lowest localized triplet excited state is much lower than that of the charge-transfer excited state, the system exhibits a short LPL duration and clear two distinct emission features originating from exciplex fluorescence and donor phosphorescence.

The high-affinity calcium sensor synaptotagmin-7 serves multiple roles in regulated exocytosis.

Synaptotagmin (Syt) proteins comprise a 17-member family, many of which trigger exocytosis in response to calcium. Historically, most studies have focused on the isoform Syt-1, which serves as the primary calcium sensor in synchronous neurotransmitter release. Recently, Syt-7 has become a topic of broad interest because of its extreme calcium sensitivity and diversity of roles in a wide range of cell types. Here, we review the known and emerging roles of Syt-7 in various contexts and stress the importance of its actions. Unique functions of Syt-7 are discussed in light of recent imaging, electrophysiological, and computational studies. Particular emphasis is placed on Syt-7-dependent regulation of synaptic transmission and neuroendocrine cell secretion. Finally, based on biochemical and structural data, we propose a mechanism to link Syt-7's role in membrane fusion with its role in subsequent fusion pore expansion via strong calcium-dependent phospholipid binding.

Backbone resonance assignments of complexes of apo human calmodulin bound to IQ motif peptides of voltage-dependent sodium channels NaV1.1, NaV1.4 and NaV1.7.

Human voltage-gated sodium (NaV) channels are critical for initiating and propagating action potentials in excitable cells. Nine isoforms have different roles but similar topologies, with a pore-forming α-subunit and auxiliary transmembrane ß-subunits. NaV pathologies lead to debilitating conditions including epilepsy, chronic pain, cardiac arrhythmias, and skeletal muscle paralysis. The ubiquitous calcium sensor calmodulin (CaM) binds to an IQ motif in the C-terminal tail of the α-subunit of all NaV isoforms, and contributes to calcium-dependent pore-gating in some channels. Previous structural studies of calcium-free (apo) CaM bound to the IQ motifs of NaV1.2, NaV1.5, and NaV1.6 showed that CaM binding was mediated by the C-domain of CaM (CaMC), while the N-domain (CaMN) made no detectable contacts. To determine whether this domain-specific recognition mechanism is conserved in other NaV isoforms, we used solution NMR spectroscopy to assign the backbone resonances of complexes of apo CaM bound to peptides of IQ motifs of NaV1.1, NaV1.4, and NaV1.7. Analysis of chemical shift differences showed that peptide binding only perturbed resonances in CaMC; resonances of CaMN were identical to free CaM. Thus, CaMC residues contribute to the interface with the IQ motif, while CaMN is available to interact elsewhere on the channel.

Organic Long-Persistent Luminescence from a Flexible and Transparent Doped Polymer.

Long-persistent luminescence (LPL) materials have a wide range of applications, such as in architectural decorations, safety signs, watch dials, and glow-in-the-dark toys. Present LPL materials based on inorganics must be processed into powders and blended with polymer matrices before use. However, micropowders of inorganic LPL materials show poor compatibility with common polymers, limiting the mechanical properties and transparency of the composites. Here, a polymer-based organic LPL (OLPL) system that is flexible, transparent, and solution processable is reported. Following low-power excitation at room temperature, this polymer-based OLPL system exhibits LPL after phosphorescence from the donor.

Calcium triggers reversal of calmodulin on nested anti-parallel sites in the IQ motif of the neuronal voltage-dependent sodium channel NaV1.2.

Several members of the voltage-gated sodium channel family are regulated by calmodulin (CaM) and ionic calcium. The neuronal voltage-gated sodium channel NaV1.2 contains binding sites for both apo (calcium-depleted) and calcium-saturated CaM. We have determined equilibrium dissociation constants for rat NaV1.2 IQ motif [IQRAYRRYLLK] binding to apo CaM (~3nM) and (Ca2+)4-CaM (~85nM), showing that apo CaM binding is favored by 30-fold. For both apo and (Ca2+)4-CaM, NMR demonstrated that NaV1.2 IQ motif peptide (NaV1.2IQp) exclusively made contacts with C-domain residues of CaM (CaMC). To understand how calcium triggers conformational change at the CaM-IQ interface, we determined a solution structure (2M5E.pdb) of (Ca2+)2-CaMC bound to NaV1.2IQp. The polarity of (Ca2+)2-CaMC relative to the IQ motif was opposite to that seen in apo CaMC-Nav1.2IQp (2KXW), revealing that CaMC recognizes nested, anti-parallel sites in Nav1.2IQp. Reversal of CaM may require transient release from the IQ motif during calcium binding, and facilitate a re-orientation of CaMN allowing interactions with non-IQ NaV1.2 residues or auxiliary regulatory proteins interacting in the vicinity of the IQ motif.