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The phosphatidylinositol-3-phosphate (PI3P) is generated by the lipid kinase VPS34, in the context of VPS34 complex I on autophagosomes or complex II on endosomes. Biochemical and structural analyses provide insights into the mechanism of both VPS34 complexes recruitment to and activation on membranes by specific Rab GTPases.

The bacterial helicase-like transcription factor HelD interacts with the RNA polymerase (RNAP) and together with the RNAP δ subunit enhances RNAP cycling. Here, the authors present the cryo-EM structures of the monomeric and dimeric Bacillus subtilis RNAP-δ-HelD complexes and suggest a model for HelD/δ-mediated RNAP recycling and putative hibernation.

The hetero-octameric protein complex, Augmin, recruits γ-Tubulin ring complex (γ-TuRC) to pre-existing microtubules (MTs) to generate branched MTs during mitosis, facilitating robust spindle assembly. However, despite a recent partial reconstitution of the human Augmin complex in vitro, the molecular basis of this recruitment remains unclear. Here, we used immuno-affinity purification of in vivo Augmin from Drosophila and cross-linking/mass spectrometry to identify distance restraints between residues within the eight Augmin subunits in the absence of any other structural information. The results allowed us to predict potential interfaces between Augmin and γ-TuRC. We tested these predictions biochemically and in the Drosophila embryo, demonstrating that specific regions of the Augmin subunits, Dgt3, Dgt5 and Dgt6 all directly bind the γ-TuRC protein, Dgp71WD, and are required for the accumulation of γ-TuRC, but not Augmin, to the mitotic spindle. This study therefore substantially increases our understanding of the molecular mechanisms underpinning MT-dependent MT nucleation.

Abstract Understanding the mechanisms of synaptic plasticity is crucial for elucidating how the brain adapts to internal and external stimuli. A key objective of plasticity is maintaining physiological activity states during perturbations by adjusting synaptic transmission through negative feedback mechanisms. However, identifying and characterizing novel molecular targets orchestrating synaptic plasticity remains a significant challenge. This study investigated the effects of tetrodotoxin (TTX)-induced synaptic plasticity within organotypic entorhino-hippocampal tissue cultures, offering insights into the functional, transcriptomic, and proteomic changes associated with network inhibition via voltage-gated sodium channel blockade. Our experiments demonstrate that TTX treatment induces substantial functional plasticity of excitatory synapses, as evidenced by increased miniature excitatory postsynaptic current (mEPSC) amplitudes and frequencies in both dentate granule cells and CA1 pyramidal neurons. Correlating transcriptomic and proteomic data, we identified novel targets for future research into homeostatic plasticity, including cytoglobin, SLIT-ROBO Rho GTPase Activating Protein 3, Transferrin receptor, and 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1. These data provide a valuable resource for future studies aiming to understand the orchestration of homeostatic plasticity by metabolic pathways in distinct cell types of the central nervous system.

Numerical models serve as an essential tool to investigate the causes and effects of Arctic sea ice changes. Evaluating the simulation capabilities of the most recent CMIP6 models in sea ice volume flux provides references for model applications and improvements. Meanwhile, reliable long-term simulation results of the ice volume flux contribute to a deeper understanding of the sea ice response to global climate change. In this study, the sea ice volume flux through six Arctic gateways over the past four decades (1979–2014) were estimated in combination of satellite observations of sea ice concentration (SIC) and sea ice motion (SIM) as well as the Pan-Arctic Ice-Ocean Modeling and Assimilation System (PIOMAS) reanalysis sea ice thickness (SIT) data. The simulation capability of 17 CMIP6 historical models for the volume flux through Fram Strait were quantitatively assessed. Sea ice volume flux simulated from the ensemble mean of 17 CMIP6 models demonstrates better performance than that from the individual model, yet IPSL-CM6A-LR and EC-Earth3-Veg-LR outperform the ensemble mean in the annual volume flux, with Taylor scores of 0.86 and 0.50, respectively. CMIP6 models display relatively robust capability in simulating the seasonal variations of volume flux. Among them, CESM2-WACCM performs the best, with a correlation coefficient of 0.96 and a Taylor score of 0.88. Conversely, NESM3 demonstrates the largest deviation from the observation/reanalysis data, with the lowest Taylor score of 0.16. The variability of sea ice volume flux is primarily influenced by SIM and SIT, followed by SIC. The extreme large sea ice export through Fram Strait is linked to the occurrence of anomalously low air temperatures, which in turn promote increased SIC and SIT in the corresponding region. Moreover, the intensified activity of Arctic cyclones and Arctic dipole anomaly could boost the southward sea ice velocity through Fram Strait, which further enhance the sea ice outflow.

Summary: Malignancies can compromise systemic innate immunity, but the underlying mechanisms are largely unknown. Here, we find that tumor-derived small extracellular vesicles (sEVs; TEVs) deliver PD-L1 to host macrophages, thereby impeding antibacterial immunity. Mice implanted with Rab27a-knockdown tumors are more resistant to bacterial infection than wild-type controls. Injection of TEVs into mice impairs macrophage-mediated bacterial clearance, increases systemic bacterial dissemination, and enhances sepsis score in a PD-L1-dependent manner. Mechanistically, TEV-packaged PD-L1 inhibits Bruton’s tyrosine kinase/PLCγ2 signaling-mediated cytoskeleton reorganization and reactive oxygen species generation, impacting bacterial phagocytosis and killing by macrophages. Neutralizing PD-L1 markedly normalizes macrophage-mediated bacterial clearance in tumor-bearing mice. Importantly, circulating sEV PD-L1 levels in patients with tumors can predict bacterial infection susceptibility, while patients with tumors treated with αPD-1 exhibit fewer postoperative infections. These findings identify a mechanism by which cancer cells dampen host innate immunity-mediated bacterial clearance and suggest targeting TEV-packaged PD-L1 to reduce bacterial infection susceptibility in tumor-bearing conditions.

Objective To detect the expression changes of interleukin-10 （IL-10） and transforming growth factor-β1 （TGF-β1） during the development of deep vein thrombosis in mice, and to explore the application value of them in thrombus age estimation. Methods The mice in the experimental group were subjected to ligation of inferior vena cava. The mice were sacrificed by excessive anesthesia at 1 d, 3 d, 5 d, 7 d, 10 d, 14 d and 21 d after ligation, respectively. The inferior vena cava segment with thrombosis was extracted below the ligation point. The mice in the control group were not ligated, and the inferior vena cava segment at the same position as the experimental group was extracted. The expression changes of IL-10 and TGF-β1 were detected by immunohistochemistry （IHC）, Western blotting and real-time qPCR. Results IHC results revealed that IL-10 was mainly expressed in monocytes in thrombosis and TGF-β1 was mainly expressed in monocytes and fibroblast-like cells in thrombosis. Western blotting and real-time qPCR showed that the relative expression levels of IL-10 and TGF-β1 in each experimental group were higher than those in the control group. The mRNA and protein levels of IL-10 reached the peak at 7 d and 10 d after ligation, respectively. The mRNA expression level at 7 d after ligation was 4.72±0.15 times that of the control group, and the protein expression level at 10 d after ligation was 7.15±0.28 times that of the control group. The mRNA and protein levels of TGF-β1 reached the peak at 10 d and 14 d after ligation, respectively. The mRNA expression level at 10 d after ligation was 2.58±0.14 times that of the control group, and the protein expression level at 14 d after ligation was 4.34±0.19 times that of the control group. Conclusion The expressions of IL-10 and TGF-β1 during the evolution of deep vein thrombosis present time-dependent sequential changes, and the expression levels of IL-10 and TGF-β1 can provide a reference basis for thrombus age estimation.

AIM: To investigate the long-term changes of corneal densitometry (CD) and its contributing elements after small incision lenticule extraction (SMILE). METHODS: Totally 31 eyes of 31 patients with mean spherical equivalent of -6.46±1.50 D and mean age 28.23±7.38y were enrolled. Full-scale examinations were conducted on all patients preoperatively and during follow-up. Visual acuity, manifest refraction, axial length, corneal thickness, corneal higher-order aberrations, and CD were evaluated. RESULTS: All surgeries were completed successfully without complications or adverse events. Ten-year safety index was 1.17±0.20 and efficacy 1.04±0.28. CD value of 0–6 mm zones in central layer was statistically significantly lower 10y postoperatively, compared with preoperative values (0–2 mmΔ=-1.62, 2–6 mmΔ=-1.24, P

Objectives: To evaluate the effectiveness of a forgiveness public health intervention at promoting forgiveness, mental health, and flourishing.Methods: Colombian students (N = 2,878) at a private, nonreligious university were exposed to a 4-week forgiveness community campaign and were assessed pre- and post-campaign.Results: Forgiveness, mental health, and flourishing outcomes showed improvements after the campaign. On average, participants reported engaging in 7.18 (SD = 3.99) of the 16 types of campaign activities. The number of types of campaign activities that participants engaged in evidenced a positive linear association with forgiveness, although some activities were more popular than others and some activities were more strongly associated with increased forgiveness. For depression, anxiety, and flourishing, engaging in more activities was generally associated with greater improvements, but the patterns were less consistent relative to forgiveness.Conclusion: This forgiveness public health intervention effectively promoted forgiveness, mental health, and flourishing. Effective campaigns in diverse communities involve promoting mental and physical health through forgiveness. However, recent conflict may hinder acceptance, necessitating political capital for leadership advocating forgiveness initiatives.

The layered hierarchy model of mysticism recognizes the unitary core present in monistic mysticism, while also acknowledging the diverse range of experiences influenced by religious principles and individual dispositions. Within Islamic mysticism, these elements are encapsulated, emphasizing a tripartite synergy involving inner knowledge of the divine unity, adherence to religious codes of conduct, and the pathway that connects exoteric actions to esoteric truths. This study delves into these complexities by examining transliminality in a sample of 1033 Iranian Muslim students. Factor analysis and exploratory graph analysis revealed three factors underlying the revised transliminality scale, each with distinct meanings. The mysticism factor demonstrated support for Islamic religiosity and spirituality, aligning with integrative self-regulation as a Muslim ideal. Conversely, the hyperesthesia factor was incongruent with these ideals, exhibiting affective maladaptation. The absorption factor was uniquely linked to creative disposition while also indicating aspects of personality and affective maladaptation. These results underscore the intricacies within both Islamic mysticism and the transliminality construct, encouraging further exploration into the intricate interplay between mysticism, transliminality, and the rich tapestry of Islamic spirituality.

[This corrects the article DOI: 10.1371/journal.pone.0238497.].

ObjectiveLeader humility has been linked to many positive outcomes but not examined in humanitarian aid work. Three studies examined the multilevel correlates, contributions, and consequences of leader humility in Medair—a large, multinational, faith-based aid organization. Study 1 examined correlates of leader humility in a sample of 308 workers and 167 leaders. Study 2 explored multilevel contributions of leader humility in 96 teams comprised of 189 workers. Study 3 utilized a subsample (50 workers, 34 leaders) to explore consequences of Time 1 leader and team humility on outcomes 6 months later.MethodParticipants completed measures of humility (general, relational, team), leader and team attributions (e.g., effectiveness, cohesion, and growth-mindedness), organizational outcomes (e.g., job engagement and satisfaction; worker and team performance), and psychological outcomes (e.g., depression, anxiety, compassion satisfaction, and flourishing).ResultsLeader and team humility contributed to multilevel positive attributions about leaders (as effective and impactful), teams (as cohesive, psychologically safe, and growth-minded), and oneself (as humble), and those attributions contributed to organizational and psychological outcomes. Teams’ shared attributions of their leader’s humility contributed to higher worker job satisfaction and team performance. Longitudinally, for workers and leaders, leader and team humility were associated with some positive organizational and psychological outcomes over time.ConclusionIn humanitarian organizations, leader humility seems to act as an attributional and motivational social contagion that affects aid personnel’s positive attributions about their leaders, teams, and themselves. In turn, these multilevel positive attributions contribute to several positive team, organizational, and psychological outcomes among workers and leaders.

Postmortem interval （PMI） estimation has always been an important and difficult issue in the field of forensic pathology. In recent years, research progress on the estimation of PMI using RNA specific variation patterns after death has been made by researchers at home and aboard. This paper summarizes the specific application methods of messenger RNA and non-coding RNA for PMI estimation based on the literatures and discusses the existing problems and development trends, in order to provide technical reference for related studies and estimation practice

Abstract We present a concise workflow to enhance the mass spectrometric detection of crosslinked peptides by introducing sequential digestion and the crosslink identification software xiSEARCH. Sequential digestion enhances peptide detection by selective shortening of long tryptic peptides. We demonstrate our simple 12‐fraction protocol for crosslinked multi‐protein complexes and cell lysates, quantitative analysis, and high‐density crosslinking, without requiring specific crosslinker features. This overall approach reveals dynamic protein–protein interaction sites, which are accessible, have fundamental functional relevance and are therefore ideally suited for the development of small molecule inhibitors.

Wine colour is an essential organoleptic property considered by consumers. In this paper, the potential effects on colour characteristics and the content of main phenolic compounds in red wine under microwave irradiation were investigated during wine storage. The results showed that the changing trend of colour characteristics of microwave-treated and untreated wines was very similar. Moreover, total phenolic compounds, total monomeric anthocyanins, main anthocyanins, main flavonoids, and main phenolic acids (gallic acid; caffeic acid; syringic acid; (+)-catechin; Cy-3-glu; Mv-3-glu) also showed similar change trends during storage. In other words, microwave irradiation had a long-term effect on the colour properties and main phenolic compounds of red wine, changes that require long-time aging in traditional processing. In terms of the studied parameters, the changes in microwave-treated wine were faster than those in untreated wine. These results showed that microwave technology, as a promising artificial aging technology, could in a short time produce red wine of similar quality to traditional aging.

Wood-inhabiting fungi are a cosmopolitan group and show a rich diversity, growing in the vegetation of boreal, temperate, subtropical, and tropical regions. Xylodon grandineus, X. punctus, and X. wenshanensis spp. nov. were found in the Yunnan–Guizhou Plateau, China, suggested here to be new fungal species in light of their morphology and phylogeny. Xylodon grandineus is characterized by a grandinioid hymenophore and ellipsoid basidiospores; X. punctus has a membranous hymenophore, a smooth hymenial surface with a speckled distribution, and absent cystidia; X. wenshanensis has a grandinioid hymenophore with a cream to slightly buff hymenial surface and cystidia of two types. Sequences of the ITS and nLSU rRNA markers of the studied samples were generated, and phylogenetic analyses were performed using the maximum likelihood, maximum parsimony, and Bayesian inference methods. After a series of phylogenetic studies, the ITS+nLSU analysis of the order Hymenochaetales indicated that, at the generic level, six genera (i.e., Fasciodontia, Hastodontia, Hyphodontia, Lyomyces, Kneiffiella, and Xylodon) should be accepted to accommodate the members of Hyphodontia sensu lato. According to a further analysis of the ITS dataset, X. grandineus was retrieved as a sister to X. nesporii; X. punctus formed a monophyletic lineage and then grouped with X. filicinus, X. hastifer, X. hyphodontinus, and X. tropicus; and X. wenshanensis was a sister to X. xinpingensis.

Aiming at constructing photoresponsive spin crossover (SCO) behavior, herein we designed a new ligand Abtz (Abtz = (E)-N-(4-((E)-phenyldiazenyl)phenyl)-1-(thiazol-4-yl)methanimine) which was decorated by a photochromic azobenzene group. Based on this photochromic ligand, a mononuclear Fe(II) SCO molecule [Fe(Abtz)3](BF4)2·(EAC)2 (1, EAC = ethyl acetate) was successfully synthesized and showed a complete one-step SCO behavior. Under continuous UV light and blue-light exposure, the cis–trans photoisomerization of both ligand Abtz and compound 1 in the liquid phase was confirmed through UV–Vis spectra. Moreover, the 1H-NMR spectra of Abtz reveal a trans–cis conversion ratio of 37%. Although the UV–Vis spectra reveal the photochromic behavior for 1 in the solution phase, the SCO behavior in the liquid state is absent according to the variable-temperature Evans method, suggesting the possible decomposition. Moreover, in the solid state, the cis–trans photoisomerization of both Abtz and 1 was not observed, due to the steric hindrance.

Objectives: To evaluate the effectiveness of a forgiveness public health intervention at promoting forgiveness, mental health, and flourishing. Methods: Colombian students (N = 2,878) at a private, nonreligious university were exposed to a 4-week forgiveness community campaign and were assessed pre- and post-campaign. Results: Forgiveness, mental health, and flourishing outcomes showed improvements after the campaign. On average, participants reported engaging in 7.18 (SD = 3.99) of the 16 types of campaign activities. The number of types of campaign activities that participants engaged in evidenced a positive linear association with forgiveness, although some activities were more popular than others and some activities were more strongly associated with increased forgiveness. For depression, anxiety, and flourishing, engaging in more activities was generally associated with greater improvements, but the patterns were less consistent relative to forgiveness. Conclusion: This forgiveness public health intervention effectively promoted forgiveness, mental health, and flourishing. Effective campaigns in diverse communities involve promoting mental and physical health through forgiveness. However, recent conflict may hinder acceptance, necessitating political capital for leadership advocating forgiveness initiatives. [ABSTRACT FROM AUTHOR]

In earthquake monitoring, an important aspect of the operational effect of earthquake intensity rapid reporting and earthquake early warning networks depends on the density and performance of the deployed seismic sensors. To improve the resolution of seismic sensors as much as possible while keeping costs low, in this article the use of multiple low-cost and low-resolution digital MEMS accelerometers is proposed to increase the resolution through the correlation average method. In addition, a cost-effective MEMS seismic sensor is developed. With ARM and Linux embedded computer technology, this instrument can cyclically store the continuous collected data on a built-in large-capacity SD card for approximately 12 months. With its real-time seismic data processing algorithm, this instrument is able to automatically identify seismic events and calculate ground motion parameters. Moreover, the instrument is easy to install in a variety of ground or building conditions. The results show that the RMS noise of the instrument is reduced from 0.096 cm/s2 with a single MEMS accelerometer to 0.034 cm/s2 in a bandwidth of 0.1–20 Hz by using the correlation average method of eight low-cost MEMS accelerometers. The dynamic range reaches more than 90 dB, the amplitude–frequency response of its input and output within −3 dB is DC −80 Hz, and the linearity is better than 0.47%. In the records from our instrument, earthquakes with magnitudes between M2.2 and M5.1 and distances from the epicenter shorter than 200 km have a relatively high SNR, and are more visible than they were prior to the joint averaging.

In Ghana, collectivism holds people together in marital relationships, even if partners are religiously different. Married partners still hurt, betray, or offend each other and might develop avoidance or vengeful (i.e., unforgiving) motives. We investigated whether religious homogamy moderated connections of personality and marriage variables to unforgiving motives. Heterosexual married couples (N = 176 heterosexual married couples; N = 352 individuals; mean marriage duration 10.89 years) participated. Most identified as Christian (83.5% males; 82.3% females) or Muslim (11.9% males; 14.3% females). Couple religious homogamy was related directly to lower unforgiving motives. Religious homogamy did not moderate the connection between some personality variables (i.e., agreeableness and trait forgivingness) and unforgiving motives. Religiously unmatched couples tended to have greater unforgiveness at higher levels of neuroticism and lower forbearing, marital satisfaction, and marital commitment relative to religiously matched couples. One implication is that couple therapists need to assess partner neuroticism, marriage climate (i.e., satisfaction and commitment), and the general tendency to forbear when offended. Those can combine to produce unforgiving relationships, which might make progress in couple therapy improbable.

As a major threat factor for female health, breast cancer (BC) has garnered a lot of attention for its malignancy and diverse molecules participating in its carcinogenesis process. Among these complex carcinogenesis processes, cell proliferation, epithelial-to-mesenchymal transition (EMT), mesenchymal-to-epithelial transition (MET), and angiogenesis are the major causes for the occurrence of metastasis and chemoresistance which account for cancer malignancy. MicroRNAs packaged and secreted in exosomes are termed “exosomal microRNAs (miRNAs)”. Nowadays, more researches have uncovered the roles of exosomal miRNAs played in BC metastasis. In this review, we recapitulated the dual actions of exosomal miRNAs exerted in the aggressiveness of BC by influencing migration, invasion, and distant metastasis. Next, we presented how exosomal miRNAs modify angiogenesis and stemness maintenance. Clinically, several exosomal miRNAs can govern the transformation between drug sensitivity and chemoresistance. Since the balance of the number and type of exosomal miRNAs is disturbed in pathological conditions, they are able to serve as instructive biomarkers for BC diagnosis and prognosis. More efforts are needed to connect the theoretical studies and clinical traits together. This review provides an outline of the pleiotropic impacts of exosomal miRNAs on BC metastasis and their clinical implications, paving the way for future personalized drugs.

Objective: Leader humility has been linked to many positive outcomes but not examined in humanitarian aid work. Three studies examined the multilevel correlates, contributions, and consequences of leader humility in Medair--a large, multinational, faith-based aid organization. Study 1 examined correlates of leader humility in a sample of 308 workers and 167 leaders. Study 2 explored multilevel contributions of leader humility in 96 teams comprised of 189 workers. Study 3 utilized a subsample (50 workers, 34 leaders) to explore consequences of Time 1 leader and team humility on outcomes 6 months later. Method: Participants completed measures of humility (general, relational, team), leader and team attributions (e.g., effectiveness, cohesion, and growthmindedness), organizational outcomes (e.g., job engagement and satisfaction; worker and team performance), and psychological outcomes (e.g., depression, anxiety, compassion satisfaction, and flourishing). Results: Leader and team humility contributed to multilevel positive attributions about leaders (as effective and impactful), teams (as cohesive, psychologically safe, and growth-minded), and oneself (as humble), and those attributions contributed to organizational and psychological outcomes. Teams' shared attributions of their leader's humility contributed to higher worker job satisfaction and team performance. Longitudinally, for workers and leaders, leader and team humility were associated with some positive organizational and psychological outcomes over time. Conclusion: In humanitarian organizations, leader humility seems to act as an attributional and motivational social contagion that affects aid personnel's positive attributions about their leaders, teams, and themselves. In turn, these multilevel positive attributions contribute to several positive team, organizational, and psychological outcomes among workers and leaders. [ABSTRACT FROM AUTHOR]