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Alternative polyadenylation (APA) is a critical post-transcriptional process that generates mRNA isoforms with distinct 3′ untranslated regions (3′ UTRs), thereby regulating mRNA localization, stability, and translational efficiency. Cell-type-specific APA extensively shapes the diversity of the cellular transcriptome, particularly during cell fate transition. Despite its recognized significance, the precise regulatory mechanisms governing cell-type-specific APA remain unclear. In this study, we uncover PQBP1 as an emerging APA regulator that actively maintains cell-specific APA profiles in neural progenitor cells (NPCs) and delicately manages the equilibrium between NPC proliferation and differentiation. Multi-omics analysis shows that PQBP1 directly interacts with the upstream UGUA elements, impeding the recruitment of the CFIm complex and influencing polyadenylation site selection within genes associated with the cell cycle. Our findings elucidate the molecular mechanism by which PQBP1 orchestrates dynamic APA changes during neurogenesis, providing valuable insights into the precise regulation of cell-type-specific APA and the underlying pathogenic mechanisms in neurodevelopmental disorders. [Display omitted] • Depletion of PQBP1 reduces NSPC proliferation and promotes neuronal differentiation • PQBP1 selectively regulates APA profiles in NSPCs • PQBP1 competes with CFIm for binding to UGUA motif and suppresses mRNA 3′ end processing • PQBP1 C-terminal truncation disrupts the RNA-binding ability and impairs neurogenesis Cell-type-specific APA extensively shapes the diversity of the cellular transcriptome, particularly during cell fate transition. Liu et al. discover PQBP1 as a novel APA regulator that actively maintains cell-specific APA profiles in neural stem/progenitor cells (NSPCs) and delicately manages the balance between NSPC proliferation and differentiation. [ABSTRACT FROM AUTHOR]

The establishment of a functional vasculature requires endothelial cells to enter quiescence during the completion of development, otherwise pathological overgrowth occurs. How such a transition is regulated remains unclear. Here, we uncover a role of Zeb1 in defining vascular quiescence entry. During quiescence acquisition, Zeb1 increases along with the progressive decline of endothelial progenitors' activities, with Zeb1 loss resulting in endothelial overgrowth and vascular deformities. RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin sequencing (ATAC-seq) analyses reveal that Zeb1 represses Wif1, thereby activating Wnt/β-catenin signaling. Knockdown of Wif1 rescues the overgrowth induced by Zeb1 deletion. Importantly, local administration of surrogate Wnt molecules in the retina ameliorates the overgrowth defects of Zeb1 mutants. These findings show a mechanism by which Zeb1 induces quiescence of endothelial progenitors during the establishing of vascular homeostasis, providing molecular insight into the inherited neovascular pathologies associated with human ZEB1 mutations, suggesting pharmacological activation of Wnt/β-catenin signaling as a potential therapeutical approach. [Display omitted] • Zeb1-Wif1-Wnt/β-catenin signaling governs endothelial progenitors' quiescence entry • Zeb1 deficiency results in vascular deformities resembling patients with PPCD • Wnt/β-catenin local activation ameliorates vascular pathologies in Zeb1 ECKO The establishment of a functional vasculature requires the quiescence entry of endothelial cells (ECs) when development is completed, otherwise, pathological overgrowth occurs. In this study, Yu et al. identify Zeb1, which acts upstream of Wnt/β-catenin signaling, to govern the quiescence of EC progenitors and the transition into homeostasis. [ABSTRACT FROM AUTHOR]

Long intergenic noncoding RNAs (lincRNAs) are crucial regulators in numerous biological processes. However, the functions and mechanisms of m6A-modified lincRNAs in neuronal development remain unclear. Here, we report an m6A-modified lincRNA, Dppa2 upstream binding RNA (Dubr), abundantly expressed at the early developmental stage of dorsal root ganglion (DRG) and cerebral cortex. Silencing Dubr impairs axon elongation of DRG neurons and axon projection and migration of cortical neurons, whereas lacking m6A modification of Dubr fully loses its functions. Mechanically, Dubr interacts with m6A-binding proteins, the YTHDF1/3 complex, through its m6A motifs to protect YTHDF1/3 from degradation via the proteasome pathway. Furthermore, Tau and Calmodulin are regulated by YTHDF1/3 and m6A-modified Dubr. Overexpression of YTHDF1/3 not only rescues the reduced Tau and Calmodulin but also restores axon elongation of DRG neurons by Dubr knockdown. This study uncovers a critical role of m6A-modified lincRNA in neuronal development by regulating the degradation of RNA-binding protein. [Display omitted] • m6A-modified lincRNA Dubr is required for neuronal development • Dubr binds and stabilizes YTHDF1/3 via its m6A modification sites • m6A-modified Dubr stabilizes the YTHDF1/3 complex and facilitates mRNA translation Huang et al. find that the m6A-modified lincRNA Dubr binds and stabilizes the YTHDF1/3 complex through its m6A modification, thereby facilitating the translation of Tau and Calmodulin, as well as maintaining subsequent axon elongation and neuronal migration. The findings provide insight into how m6A-modified lincRNA orchestrates neuronal development. [ABSTRACT FROM AUTHOR]

Summary Subcellular targeting and local translation of mRNAs are critical for axon development. However, the precise local control of mRNA translation requires investigation. We report that the Fmr1 -encoded protein, FMRP-mediated axonal delivery of miR-181d negatively regulates axon elongation by locally targeting the transcripts of MAP1B ( Map1b ) and calmodulin ( Calm1 ) in primary sensory neurons. miR-181d affected the local synthesis of MAP1B and calmodulin in axons. FMRP was associated with miR-181d, Map1b , and Calm1 . Both FMRP deficiency in Fmr1 I304N mice and Fmr1 knockdown impeded the axonal delivery of miR-181d, Map1b , and Calm1 and reduced the protein levels of MAP1B and calmodulin in axons. Furthermore, nerve growth factor (NGF) induced Map1b and Calm1 release from FMRP and miR-181d-repressing granules, thereby promoting axon elongation. Both miR-181d overexpression and FMRP knockdown impaired NGF-induced axon elongation. Our study reveals a mechanism for the local regulation of translation by miR-181d and FMRP during axon development. [ABSTRACT FROM AUTHOR]

Abstract: Studies confirm that the lipid accumulation product (LAP), which is based on the waist circumference and fasting serum triglycerides, is highly related to cardiovascular and metabolic diseases. Nonalcoholic fatty liver disease is a hepatic manifestation of metabolic syndrome and closely correlated with the alanine aminotransferase (ALT) elevation. Abdominal obesity and dyslipidemia are the important risk factors for nonalcoholic fatty liver disease. Our aim was to examine the correlation between the LAP and ALT in apparently healthy adults. We conducted a cross-sectional study of 587 adults. The blood pressure, anthropometric measurements, fasting and postload glucose, insulin, fasting lipid profile, and liver enzymes were measured. The LAP was calculated. For each gender, the subjects were divided into 3 groups according to the ALT level. The correlation between the LAP and ALT was analyzed. The LAP increased progressively across the ALT tertiles. A Pearson correlation analysis demonstrated that the LAP positively associated with the ALT in men and women (both P < .05) but independently related to the ALT only in men. Furthermore, after adjusting for the other confounding factors, the subjects in the upper quartile of LAP was 3.61 times more likely to show ALT elevation compared with those in the lower quartiles in men. In addition, in men, the LAP was considered as the best marker to predict increased ALT. Our findings suggested that the LAP was independently correlated with the ALT but only in men. The LAP was the main risk marker and might be superior to other variables in recognizing increased ALT. [Copyright &y& Elsevier]

Abstract: Various studies have revealed anaerobic ammonium oxidation (anammox) as a very attractive alternative process suitable for nitrogen removal from wastewater. Here we investigated anammox bacteria in eight different nitrogen removal reactors. The diversity and abundance of anammox bacteria were determined by the 16S rRNA gene analysis, fluorescence in situ hybridization with specific probes and real-time quantitative PCR (qPCR). In these reactors, at least eight unique near full length anammox 16S rRNA gene sequences were detected, which were distributed over two genera; Candidati Brocadia and Kuenenia. FISH results confirmed that only one anammox bacterium dominated the community in each of the eight reactors investigated in this study. qPCR analysis revealed that anammox bacteria were present in seven of the reactors in the order of 109 cells/ml and 107 cells/ml in reactor A1. The dominant and divergent Brocadia-like anammox phylotype in one reactor represented a novel species for which we propose the name Candidatus Brocadia sinica. Taken together, these results indicated that a single seeding source could be used to seed anammox reactors designed to treat different types of wastewater, which could lead to a faster start-up of bioreactors. [ABSTRACT FROM AUTHOR]

Abstract: There are two major secretory pathways in neurons, the regulated pathway and the constitutive pathway. Neuropeptides and other regulated secretory proteins are known to be sorted into large dense-core vesicles of the regulated pathway in the trans-Golgi network and are secreted upon stimulus-induced increases in intracellular Ca2+. The newly synthesized cell surface receptors are usually sorted into microvesicles of the constitutive pathway and inserted into the plasma membrane by spontaneous exocytosis. Small-diameter sensory neurons in dorsal root ganglia and pheochromocytoma cells express neuropeptides (e.g., substance P) and several neuropeptide receptors including opioid receptors. The μ-opioid receptors are delivered to the cell surface through the constitutive pathway, whereas another type of opioid receptor, the δ-opioid receptor, is often found in the membrane of large dense-core vesicles and can be inserted into the plasma membrane when exocytosis occurs. Recent studies show that sequences with opposite electrical polarity within the prohormones of substance P are essential for their sorting into large dense-core vesicles. Moreover, the δ-opioid receptor is sorted into large dense-core vesicles by its interaction with protachykinin, a prohormone of substance P. These findings provide insight into the molecular mechanisms that determine the sorting and trafficking of neuropeptides and neuropeptide receptors in neurons. [Copyright &y& Elsevier]

Abstract: A new stability evaluating system for ANAMMOX comprising three instability indices i.e. coefficient of variation ratio, coefficient of range ratio and coefficient of regression function derivative was established. Three lab-scale ANAMMOX reactors viz upflow anaerobic sludge blanket (UASB) reactor, upflow stationary fixed film (USFF) reactor and anaerobic sequencing batch reactor (ASBR) were compared for their stability based on the established criterion against the hydraulic and substrate concentration shocks. The results showed that all ANAMMOX reactors under investigation were more tolerant to the hydraulic shock than substrate concentration shock. The UASB reactor was the most stable reactor configuration towards substrate concentration shock, followed by the USFF reactor and ASBR. However, the ASBR proved the most tolerant to hydraulic shock, followed by the UASB reactor and USFF reactor. In terms of stability, UASB reactor was more suitable configuration compared with USFF reactor. The instability indices proved to be effective and explicit for the evaluation of ANAMMOX systems. [Copyright &y& Elsevier]

Nociceptive circuitry processes the signals evoked by activating specialized peripheral sensory receptors for pain perception. Recent studies show that the neuronal phenotypes in the dorsal root ganglia and spinal dorsal horn are determined by distinct sets of transcription factors during development. Anatomical analyses with genetic approaches demonstrate that each subset of nociceptive sensory neurons has topographically distinct circuits at both spinal and brain levels. Moreover, the sensitivity of primary afferents can be rapidly regulated not only by phosphorylation of receptors, ion channels and associated regulatory proteins but also by stimulus-induced cell surface expression of G-protein-coupled receptors. In chronic pain states the molecular characteristics of spinal nociceptive circuits are altered, enabling normal peripheral stimuli to induce pain hypersensitivity. [Copyright &y& Elsevier]

Changes in the number of receptors on the cell surface lead to modulations of physiological functions and pharmacological responses of neurons. Recent studies show that δ-opioid peptide (DOP) and μ-opioid peptide (MOP) receptors have distinct subcellular localizations in neurons. In nociceptive small neurons in the dorsal root ganglia, DOP receptors are sorted into neuropeptide-containing secretory vesicles, enabling the stimulus-induced cell surface expression of these receptors. MOP receptors are constitutively expressed on the cell surface. The physical interaction between DOP receptors and MOP receptors seems to be an important mechanism for the modulation of receptor functions. Experiments in animals show that MOP-receptor-mediated spinal analgesia is enhanced and morphine tolerance does not develop when DOP receptor functions are pharmacologically or genetically attenuated. Thus, the delivery and trafficking of DOP receptors are crucial processes that modulate opioid analgesia and tolerance. [Copyright &y& Elsevier]

Long intergenic noncoding RNAs (lincRNAs) are critical regulators involved in diverse biological processes. However, the roles and related mechanisms of lincRNAs in axon development are largely unknown. Here we report an axon-enriched lincRNA regulating axon elongation, referred to as ALAE. Profiling of highly expressed lincRNAs detected abundant and enriched ALAE in the axons of dorsal root ganglion (DRG) neurons, where it locally promoted axon elongation. Mechanically, ALAE directly interacted with the KH3–4 domains of KH-type splicing regulatory protein (KHSRP) and impeded its association with growth-associated protein 43 (Gap43) mRNA. Knockdown of ALAE reduced the protein but not the mRNA level of GAP43 in the axons of DRG neurons. Furthermore, local disruption of the interaction between ALAE and KHSRP in the axon significantly inhibited Gap43 mRNA translation, impairing axon elongation. This study implies crucial roles of axon-enriched lincRNAs in spatiotemporal regulation of local translation during axon development. [Display omitted] • ALAE is an axon-enriched lincRNA required locally for axon elongation • ALAE interacts with the KH3–4 domains of KHSRP through AU-rich elements • ALAE acts as a RNA decoy to prevent translational repression of KHSRP on Gap43 • Impaired ALAE -KHSRP interaction locally inhibits Gap43 translation and axon elongation Wei et al. show that lincRNA ALAE interacts with KHSRP and acts as a decoy to locally prevent translational suppression of GAP43 in axons, maintaining protein synthesis and subsequent axon elongation. The findings provide insights into how axon-enriched lincRNAs spatiotemporally orchestrate local translation of mRNAs during axon development. [ABSTRACT FROM AUTHOR]

Abstract: Piperazine (PZ) and phosphates as additives were added into an aqueous N-methylmonoethanolamine (MMEA) to form complex absorbents, respectively. Performances of CO2 capture by the complex absorbents were evaluated in a bubble column reactor. Reaction mechanisms and activations of the additives were presented theoretically. Effects of type and concentration of additives, and gas flowrates on volumetric mass transfer coefficient were investigated, and effects of orifice size of the gas sparger and stirring rates on average absorption velocity were also discussed. Results show that CO2 loadings of MMEA–PZ and MMEA–K3PO4 complex absorbents were larger than that of single MMEA and MEA absorbents. The MMEA–PZ complex absorbent gave a highest CO2 loading in all complex absorbents. The overall mass transfer coefficient increased, subsequently reached a maximum and then decreased with the increase of K3PO4 concentration in the complex absorbent. The overall mass transfer coefficient increased with the increase of the gas flow rates. Average absorption velocities increased with the decrease of the orifice size and with the increase of the orifice numbers. The average absorption velocities in moderate intensity of stirring rates were higher than that in the high intensity of stirring rates. [Copyright &y& Elsevier]

Abstract: The impacts of transient overloads on the performance of a laboratory-scale anaerobic ammonium oxidation (ANAMMOX) anaerobic baffled reactor was studied by increasing the substrate concentration or inflow rate to 1.5–3.0 times above normal values. These shocks, with the exception of the highest substrate shock, weakened the nitrogen removal efficiency (NRE) but improved the nitrogen removal rate by 0.01–0.18gl−1 h−1. The communities and the location of the sludge may be altered by distinct types of shocks. The substrate vibration data showed that the reactor was unresponsive to hydraulic shocks but sensitive to substrate shocks and the former compartments were more susceptible to the shocks. In the inhibition period, the pH and NRE of the reactor were related to the residual ammonium and free ammonia (FA) and FA was a factor in the reactor fluctuations. The Gaussian model proposed to describe the shocks response fits the experimental data well. [Copyright &y& Elsevier]

Abstract: The aerobic ammonia oxidation is an important process for nitrogen removal from wastewater with high ammonia concentration. Here, we investigated the metabolic properties of a mixed culture of aerobic ammonia oxidizers and determined its optimal reaction conditions. The maximum specific rate of formation of the culture was 14.9mgNmg(protein)−1 d−1. The ammonia oxidation capacity was positively correlated with the microbial biomass concentration. Haldane model showed that the half-saturation constant (K s) for of the culture was 78.5mgL−1, and the inhibition constant (K i) for was 393.4mgL−1. The acetic acid and beef extract had significant inhibitory effects on ammonia oxidation, while there was little effect of methanol and glucose on ammonia oxidation. Orthogonal experiments with range analysis, variance analysis, factor contribution analysis and response surface analysis confirmed the optimal reaction conditions for ammonia oxidation to be 30–32°C, pH 7.8–8.0, and 150–200mgL−1 concentration. [Copyright &y& Elsevier]

Abstract: Vigorous anaerobic ammonium oxidation (anammox) activity was realized by seeding with diverse sludge contents. Granules taken from a 2-year old methanogenic reactor loaded with high organic and methanol contents were used as inoculum to enrich anammox biomass in a 1.1L upflow anaerobic sludge blanket reactor. Anammox activity appeared after an operation of 83d resulting in the final nitrogen removal rate of 11.7kgNm−3 d−1 with the efficient granulation of anammox sludge. The analysis based on 16S rDNA sequencing confirmed that Candidatus “Brocadia” was the dominant population in the enriched biomass. [Copyright &y& Elsevier]