Global supply chains amplify economic costs of future extreme heat risk.

Evidence shows a continuing increase in the frequency and severity of global heatwaves1,2, raising concerns about the future impacts of climate change and the associated socioeconomic costs3,4. Here we develop a disaster footprint analytical framework by integrating climate, epidemiological and hybrid input-output and computable general equilibrium global trade models to estimate the midcentury socioeconomic impacts of heat stress. We consider health costs related to heat exposure, the value of heat-induced labour productivity loss and indirect losses due to economic disruptions cascading through supply chains. Here we show that the global annual incremental gross domestic product loss increases exponentially from 0.03 ± 0.01 (SSP 245)-0.05 ± 0.03 (SSP 585) percentage points during 2030-2040 to 0.05 ± 0.01-0.15 ± 0.04 percentage points during 2050-2060. By 2060, the expected global economic losses reach a total of 0.6-4.6% with losses attributed to health loss (37-45%), labour productivity loss (18-37%) and indirect loss (12-43%) under different shared socioeconomic pathways. Small- and medium-sized developing countries suffer disproportionately from higher health loss in South-Central Africa (2.1 to 4.0 times above global average) and labour productivity loss in West Africa and Southeast Asia (2.0-3.3 times above global average). The supply-chain disruption effects are much more widespread with strong hit to those manufacturing-heavy countries such as China and the USA, leading to soaring economic losses of 2.7 ± 0.7% and 1.8 ± 0.5%, respectively.

Ubiquitination of the GluA1 Subunit of AMPA Receptors Is Required for Synaptic Plasticity, Memory, and Cognitive Flexibility.

Activity-dependent changes in the number of AMPA-type glutamate receptors (AMPARs) at the synapse underpin the expression of LTP and LTD, cellular correlates of learning and memory. Post-translational ubiquitination has emerged as a key regulator of the trafficking and surface expression of AMPARs, with ubiquitination of the GluA1 subunit at Lys-868 controlling the post-endocytic sorting of the receptors into the late endosome for degradation, thereby regulating their stability at synapses. However, the physiological significance of GluA1 ubiquitination remains unknown. In this study, we generated mice with a knock-in mutation in the major GluA1 ubiquitination site (K868R) to investigate the role of GluA1 ubiquitination in synaptic plasticity, learning, and memory. Our results reveal that these male mice have normal basal synaptic transmission but exhibit enhanced LTP and deficits in LTD. They also display deficits in short-term spatial memory and cognitive flexibility. These findings underscore the critical roles of GluA1 ubiquitination in bidirectional synaptic plasticity and cognition in male mice.SIGNIFICANCE STATEMENT Subcellular targeting and membrane trafficking determine the precise number of AMPA-type glutamate receptors at synapses, processes that are essential for synaptic plasticity, learning, and memory. Post-translational ubiquitination of the GluA1 subunit marks AMPARs for degradation, but its functional role in vivo remains unknown. Here we demonstrate that the GluA1 ubiquitin-deficient mice exhibit an altered threshold for synaptic plasticity accompanied by deficits in short-term memory and cognitive flexibility. Our findings suggest that activity-dependent ubiquitination of GluA1 fine-tunes the optimal number of synaptic AMPARs required for bidirectional synaptic plasticity and cognition in male mice. Given that increases in amyloid-ß cause excessive ubiquitination of GluA1, inhibiting that GluA1 ubiquitination may have the potential to ameliorate amyloid-ß-induced synaptic depression in Alzheimer's disease.

Signaling Transduction Pathways and G-Protein-Coupled Receptors in Different Stages of the Embryonic Diapause Termination Process in Artemia.

Artemia is a widely distributed small aquatic crustacean, renowned for its ability to enter a state of embryonic diapause. The embryonic diapause termination (EDT) is closely linked to environmental cues, but the precise underlying mechanisms remain elusive. In this study, ATAC-seq and RNA-seq sequencing techniques were employed to explore the gene expression profiles in Artemia cysts 30 min after EDT. These profiles were compared with those during diapause and 5 h after EDT. The regulatory mechanisms governing the EDT process were analyzed through Gene Ontology (GO) enrichment analysis of differentially expressed genes. Furthermore, the active G-protein-coupled receptors (GPCRs) were identified through structural analysis. The results unveiled that the signaling transduction during EDT primarily hinges on GPCRs and the cell surface receptor signaling pathway, but distinct genes are involved across different stages. Hormone-mediated signaling pathways and the tachykinin receptor signaling pathway exhibited heightened activity in the '0-30 min' group, whereas the Wnt signaling pathway manifested its function solely in the '30 min-5 h' group. These results imply a complete divergence in the mechanisms of signal regulation during these two stages. Moreover, through structural analysis, five GPCRs operating at different stages of EDT were identified. These findings provide valuable insights into the signal regulation mechanisms governing Artemia diapause.

Bimetallic iron-nickel phosphide as efficient peroxymonosulfate activator for tetracycline hydrochloride degradation: Performance and mechanism.

Sulfate radical-based advanced oxidation processes with (SR-AOPs) are widely employed to degrade organic pollutants due to their high efficiency, cost-effectiveness and safety. In this study, a highly active and stable FeNiP was successfully prepared by reduction and heat treatment. FeNiP exhibited high performance of peroxymonosulfate (PMS) activation for tetracycline hydrochloride (TC) removal. Over a wide pH range, an impressive TC degaradation efficiency 97.86% was achieved within 60 min employing 0.1 g/L FeNiP and 0.2 g/L PMS at room temperature. Both free radicals of SO4·-, ·OH, ·O2- and non-free radicals of 1O2 participated the TC degradation in the FeNiP/PMS system. The PMS activation ability was greatly enhanced by the cycling between Ni and Fe bimetal, and the active site regeneration was achieved due to the existence of the negatively charged Pn-. Moreover, the FeNiP/PMS system exhibited substantial TC degradation levels in both simulated real-world disturbance scenarios and practical water tests. Cycling experiments further affirmed the robust stability of FeNiP catalyst, demonstrating sustained degradation efficiency of approximately 80% even after four cycles. These findings illuminate its promising potential across natural water bodies, presenting an innovative catalyst construction approach for PMS activation in the degradation of antibiotic pollutants.

Defective nitrogen doped carbon material derived from nano-ZIF-8 for enhanced in-situ H2O2 generation and tetracycline hydrochloride degradation in electro-Fenton system.

Tetracycline hydrochloride (TC) accumulates in large quantities in the water environment, causing a serious threat to human health and ecological environment safety. This research focused on developing cost-effective catalysts with high 2e- selectivity for electro-Fenton (EF) technology, a green pollution treatment method. Defective nitrogen-doped porous carbon (d-NPC) was prepared using the metal-organic framework as the precursor to achieve in-situ H2O2 production and self-decomposition into high activity ·OH for degradation of TC combined with Co2+/Co3+. The d-NPC produced 172.1 mg L-1 H2O2 within 120 min, and could degrade 96.4% of TC in EF system. The self-doped defects and graphite-nitrogen in d-NPC improved the oxygen reduction performance and increased the H2O2 yield, while pyridine nitrogen could catalyze H2O2 to generate ·OH. The possible pathway of TC degradation was also proposed. In this study, defective carbon materials were prepared by ball milling, which provided a new strategy for efficient in-situ H2O2 production and the degradation of pollutants.

Ultra-high flux mesh membranes coated with tannic acid-ZIF-8@MXene composites for efficient oil-water separation.

Oil/water separation has become a global concern due to the increasing discharge of multi-component harmful oily wastewater. Super wetting membranes have been shown to be an effective material for oil/water separation. Ultra-high flux stainless-steel meshes (SSM) with superhydrophilicity and underwater superoleophobicity were fabricated by tannic acid (TA) modified ZIF-8 nanoparticles (TZIF-8) and two-dimensional MXene materials for oil/water separation. The TZIF-8 increased the interlayer space of MXene, enhancing the flux permeation (69,093 L m-2h-1) and rejection of the composite membrane (TZIF-8@MXene/SSM). The TZIF-8@MXene/SSM membrane showed an underwater oil contact angle of 154.2°. The membrane maintained underwater superoleophobic after stability and durability tests, including various pH solutions, organic solvents, reusability, etc. In addition, the oil/water separation efficiency of TZIF-8@MXene/SSM membranes was higher than 99% after treatment in harsh conditions and recycling. The outstanding anti-fouling, stability, durability, and recyclability properties of TZIF-8@MXene/SSM membrane highlight the remarkable potential of membranes for complex oil/water separation process.

Leucine-rich repeat extensin proteins regulate plant salt tolerance in Arabidopsis.

The perception and relay of cell-wall signals are critical for plants to regulate growth and stress responses, but the underlying mechanisms are poorly understood. We found that the cell-wall leucine-rich repeat extensins (LRX) 3/4/5 are critical for plant salt tolerance in Arabidopsis The LRXs physically associate with the RAPID ALKALINIZATION FACTOR (RALF) peptides RALF22/23, which in turn interact with the plasma membrane-localized receptor-like protein kinase FERONIA (FER). The lrx345 triple mutant as well as fer mutant plants display retarded growth and salt hypersensitivity, which are mimicked by overexpression of RALF22/23 Salt stress promotes S1P protease-dependent release of mature RALF22 peptides. Treatment of roots with mature RALF22/23 peptides or salt stress causes the internalization of FER. Our results suggest that the LRXs, RALFs, and FER function as a module to transduce cell-wall signals to regulate plant growth and salt stress tolerance.

A domesticated Harbinger transposase forms a complex with HDA6 and promotes histone H3 deacetylation at genes but not TEs in Arabidopsis.

In eukaryotes, histone acetylation is a major modification on histone N-terminal tails that is tightly connected to transcriptional activation. HDA6 is a histone deacetylase involved in the transcriptional regulation of genes and transposable elements (TEs) in Arabidopsis thaliana. HDA6 has been shown to participate in several complexes in plants, including a conserved SIN3 complex. Here, we uncover a novel protein complex containing HDA6, several Harbinger transposon-derived proteins (HHP1, SANT1, SANT2, SANT3, and SANT4), and MBD domain-containing proteins (MBD1, MBD2, and MBD4). We show that mutations of all four SANT genes in the sant-null mutant cause increased expression of the flowering repressors FLC, MAF4, and MAF5, resulting in a late flowering phenotype. Transcriptome deep sequencing reveals that while the SANT proteins and HDA6 regulate the expression of largely overlapping sets of genes, TE silencing is unaffected in sant-null mutants. Our global histone H3 acetylation profiling shows that SANT proteins and HDA6 modulate gene expression through deacetylation. Collectively, our findings suggest that Harbinger transposon-derived SANT domain-containing proteins are required for histone deacetylation and flowering time control in plants.

A plant RNA virus activates selective autophagy in a UPR-dependent manner to promote virus infection.

Autophagy is an evolutionarily conserved pathway in eukaryotes that delivers unwanted cytoplasmic materials to the lysosome/vacuole for degradation/recycling. Stimulated autophagy emerges as an integral part of plant immunity against intracellular pathogens. In this study, we used turnip mosaic virus (TuMV) as a model to investigate the involvement of autophagy in plant RNA virus infection. The small integral membrane protein 6K2 of TuMV, known as a marker of the virus replication site and an elicitor of the unfolded protein response (UPR), upregulates the selective autophagy receptor gene NBR1 in a UPR-dependent manner. NBR1 interacts with TuMV NIb, the RNA-dependent RNA polymerase of the virus replication complex (VRC), and the autophagy cargo receptor/adaptor protein ATG8f. The NIb/NBR1/ATG8f interaction complexes colocalise with the 6K2-stained VRC. Overexpression of NBR1 or ATG8f enhances TuMV replication, and deficiency of NBR1 or ATG8f inhibits virus infection. In addition, ATG8f interacts with the tonoplast-specific protein TIP1 and the NBR1/ATG8f-containing VRC is enclosed by the TIP1-labelled tonoplast. In TuMV-infected cells, numerous membrane-bound viral particles are evident in the vacuole. Altogether these results suggest that TuMV activates and manipulates UPR-dependent NBR1-ATG8f autophagy to target the VRC to the tonoplast to promote viral replication and virion accumulation.

Role of lysophosphatidic acid in vascular smooth muscle cell proliferation.

Lysophosphatidic acid (LPA) is an important lipid molecule for signal transduction in cell proliferation. Although the effects of LPA on vascular smooth muscle (VSM) cell growth have been reported previously, the underlying mechanisms of its action are not fully understood. The present study was undertaken to investigate the effects of some inhibitors of different protein kinases and other molecular targets on LPA-induced DNA synthesis as well as gene expression in the aortic VSM cells. The DNA synthesis was studied by the [3H]thymidine incorporation method and the gene expression was investigated by the real-time PCR technique. It was observed that the LPA-induced DNA synthesis was attenuated by inhibitors of protein kinase C (PKC) (staurosporine, calphostin C, and bisindolylmaleimide), phosphoinositide 3-kinase (PI3K) (wortmannin and LY294002), and ribosomal p70S6 kinase (p70S6K) (rapamycin). The inhibitors of guanine protein coupled receptors (GPCR) (pertussis toxin), phospholipase C (PLC) (U73122 and D609), and sodium-hydrogen exchanger (NHE) (amiloride and dimethyl amiloride) were also shown to depress the LPA-induced DNA synthesis. Furthermore, gene expressions for PLC ß1 isoform, PKC δ and ε isoforms, casein kinase II ß isoform, and endothelin-1A receptors were elevated by LPA. These results suggest that the LPA-induced proliferation of VSM cells is mediated through the activation of GPCR and multiple protein kinases as well as gene expressions of some of their specific isoforms.

A protein complex regulates RNA processing of intronic heterochromatin-containing genes in Arabidopsis.

In several eukaryotic organisms, heterochromatin (HC) in the introns of genes can regulate RNA processing, including polyadenylation, but the mechanism underlying this regulation is poorly understood. By promoting distal polyadenylation, the bromo-adjacent homology (BAH) domain-containing and RNA recognition motif-containing protein ASI1 and the H3K9me2-binding protein EDM2 are required for the expression of functional full-length transcripts of intronic HC-containing genes in Arabidopsis Here we report that ASI1 and EDM2 form a protein complex in vivo via a bridge protein, ASI1-Immunoprecipitated Protein 1 (AIPP1), which is another RNA recognition motif-containing protein. The complex also may contain the Pol II CTD phosphatase CPL2, the plant homeodomain-containing protein AIPP2, and another BAH domain protein, AIPP3. As is the case with dysfunction of ASI1 and EDM2, dysfunction of AIPP1 impedes the use of distal polyadenylation sites at tested intronic HC-containing genes, such as the histone demethylase gene IBM1, resulting in a lack of functional full-length transcripts. A mutation in AIPP1 causes silencing of the 35S-SUC2 transgene and genome-wide CHG hypermethylation at gene body regions, consistent with the lack of full-length functional IBM1 transcripts in the mutant. Interestingly, compared with asi1, edm2, and aipp1 mutations, mutations in CPL2, AIPP2, and AIPP3 cause the opposite effects on the expression of intronic HC-containing genes and other genes, suggesting that CPL2, AIPP2, and AIPP3 may form a distinct subcomplex. These results advance our understanding of the interplay between heterochromatic epigenetic modifications and RNA processing in higher eukaryotes.

The Modulation of Reward and Habit Systems by Acupuncture in Adolescents with Internet Addiction.

Purpose: Acupuncture is an effective therapy for Internet addiction (IA). However, the underlying mechanisms of acupuncture in relieving compulsive Internet use remain unknown. Neuroimaging studies have demonstrated the role of the ventral striatum (VS) in the progress of IA; hence, the aim of this study was to explore the effects of acupuncture on the resting-state functional connectivity (rsFC) and relevant network of VS in IA. Methods: Twenty-seven IA individuals and 30 demographically matched healthy control subjects (HCs) were recruited in this study. We acquired the functional magnetic resonance imaging (fMRI) data in IA subjects before and after 40 days of acupuncture treatment. Seed-to-voxel and ROI-to-ROI analyses were applied to detect the rsFC alterations of the VS and related network in IA subjects and to investigate the modulation effect of acupuncture on the rsFC. Results: Compared with HCs, IA subjects exhibited enhanced rsFC of the right ventral rostral putamen (VRP) with the left orbitofrontal cortex (OFC), premotor cortex (PMC), cerebellum, and right ventromedial prefrontal cortex (vmPFC). In the network including these five ROIs, IA also showed increased ROI-to-ROI rsFC. Using a paired t-test in IA subjects before and after 40 days of acupuncture, the increased ROI-to-ROI rsFC was decreased (normalized to HC) with acupuncture, including the rsFC of the right VRP with the left OFC, PMC, and cerebellum, and the rsFC of the left cerebellum with the left OFC, PMC, and right vmPFC. Furthermore, the change in rsFC strength between the right VRP and left cerebellum in IA individuals was found positively correlated with the Internet craving alleviation after acupuncture. Conclusions: These findings verified the modulation effect of acupuncture on functional connectivity of reward and habit systems related to the VS in IA individuals, which might partly represent the underlying mechanisms of acupuncture on IA.

High-performance position-sensitive detector based on the lateral photovoltaic effect in MoSe2/p-Si junctions.

Optoelectronic position-sensitive detectors (PSDs) based on the lateral photovoltaic effect (LPE) have been a focus of research due to their ability to detect very small displacements. In this paper, we investigate the LPE properties of MoSe2/p-Si junctions prepared using pulsed laser deposition. The LPE shows a good linear dependence with the position of the laser spot. A large positional sensitivity and a fast optical relaxation time of 563 mV mm-1 and 2 µs, respectively, were observed in the MoSe2 (10 nm)/p-Si junction. The influence of the laser power and the wavelength on the LPE suggests that the observed response originates from the photoelectric effect. The large positional sensitivity and fast relaxation time of the LPE make the MoSe2/p-Si junction a promising candidate for PSDs.

The UPR branch IRE1-bZIP60 in plants plays an essential role in viral infection and is complementary to the only UPR pathway in yeast.

The unfolded protein response (UPR) signaling network encompasses two pathways in plants, one mediated by inositol-requiring protein-1 (IRE1)-bZIP60 mRNA and the other by site-1/site-2 proteases (S1P/S2P)-bZIP17/bZIP28. As the major sensor of UPR in eukaryotes, IRE1, in response to endoplasmic reticulum (ER) stress, catalyzes the unconventional splicing of HAC1 in yeast, bZIP60 in plants and XBP1 in metazoans. Recent studies suggest that IRE1p and HAC1 mRNA, the only UPR pathway found in yeast, evolves as a cognate system responsible for the robust UPR induction. However, the functional connectivity of IRE1 and its splicing target in multicellular eukaryotes as well as the degree of conservation of IRE1 downstream signaling effectors across eukaryotes remains to be established. Here, we report that IRE1 and its substrate bZIP60 function as a strictly cognate enzyme-substrate pair to control viral pathogenesis in plants. Moreover, we show that the S1P/S2P-bZIP17/bZIP28 pathway, the other known branch of UPR in plants, does not play a detectable role in virus infection, demonstrating the distinct function of the IRE1-bZIP60 pathway in plants. Furthermore, we provide evidence that bZIP60 and HAC1, products of the enzyme-substrate duet, rather than IRE1, are functionally replaceable to cope with ER stress in yeast. Taken together, we conclude that the downstream signaling of the IRE1-mediated splicing is evolutionarily conserved in yeast and plants, and that the IRE1-bZIP60 UPR pathway not only confers overlapping functions with the other UPR branch in fundamental biology but also may exert a unique role in certain biological processes such as virus-plant interactions.

Upper semicontinuity of pullback attractors for the 3D nonautonomous Benjamin-Bona-Mahony equations.

We will study the upper semicontinuity of pullback attractors for the 3D nonautonomouss Benjamin-Bona-Mahony equations with external force perturbation terms. Under some regular assumptions, we can prove the pullback attractors A(ε)(t) of equation, u(t)-Δu(t)-νΔu+∇·(-->)F(u)=εg(x,t), x ∈ Ω, converge to the global attractor A of the above-mentioned equation with ε = 0 for any t ∈ R.

Genetic polymorphism in HTR2A rs6313 is associated with internet addiction disorder.

Introduction: Internet addiction disorder (IAD) has grown into public health concern of global proportions. Previous studies have indicated that individuals with IAD may exhibit altered levels of serotonin and dopamine, which are known to play crucial roles in depression, anxiety, impulsivity, and addiction. Therefore, polymorphisms in the receptors that mediate the effects of serotonin and dopamine and affect their functional states as well as their activities are suspect. In this study, we aimed to investigate the association between IAD and rs6313 (T102C) polymorphism in the serotonin 2A receptor (5-HT2A) gene, (HTR2A). Methods: Twenty patients with IAD and twenty healthy controls (HCs) were included in this study. Young's Internet Addiction Test (IAT), Self-Rating Anxiety Scale, Self-Rating Depression Scale, Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Barratt Impulse Scale, Pittsburgh Sleep Quality Index (PSQI), and Social Support Rating Scale (SSRS) were used to assess the severity of internet addiction, mental status, impulsive traits, sleep quality, and social support. Genotyping was performed to identify rs6313 polymorphisms in the HTR2A gene of all participants. Results: The frequencies of the C and T alleles of HTR2A T102C were 28% and 72% in the IAD group and 53% and 47% in the HCs group, respectively, indicating that the differences between these two groups were significant. No significant difference was observed in the distribution of the CC, CT, and TT genotypes of HTR2A gene T102C between the IAD and the HCs groups. Additionally, there was no difference in the distribution of the frequencies of the HTR2A gene T102C CC and CT+TT genotypes between the two groups. However, the distribution between the TT and CC+CT genotypes showed an apparent statistical difference in the HTR2A gene T102C between the two groups. Correlation analysis indicated that the IAT score was positively correlated with the Y-BOCS and BIS scores for the CC+CT genotype in patients with IAD. Moreover, the IAT score was positively correlated with the PSQI score in patients with IAD carrying the TT genotype. Conclusion: The present study demonstrates that rs6313 in HTR2A is associated with IAD, and that the T allele of rs6313 in HTR2A may be a risk factor for IAD.

Reconstruction of Metabolic-Protein Interaction Integrated Network of Eriocheir sinensis and Analysis of Ecdysone Synthesis.

Integrated networks have become a new interest in genome-scale network research due to their ability to comprehensively reflect and analyze the molecular processes in cells. Currently, none of the integrated networks have been reported for higher organisms. Eriocheir sinensis is a typical aquatic animal that grows through ecdysis. Ecdysone has been identified to be a crucial regulator of ecdysis, but the influence factors and regulatory mechanisms of ecdysone synthesis in E. sinensis are still unclear. In this work, the genome-scale metabolic network and protein-protein interaction network of E. sinensis were integrated to reconstruct a metabolic-protein interaction integrated network (MPIN). The MPIN was used to analyze the influence factors of ecdysone synthesis through flux variation analysis. In total, 236 integrated reactions (IRs) were found to influence the ecdysone synthesis of which 16 IRs had a significant impact. These IRs constitute three ecdysone synthesis routes. It is found that there might be alternative pathways to obtain cholesterol for ecdysone synthesis in E. sinensis instead of absorbing it directly from the feeds. The MPIN reconstructed in this work is the first integrated network for higher organisms. The analysis based on the MPIN supplies important information for the mechanism analysis of ecdysone synthesis in E. sinensis.

Maize heat shock proteins-prospection, validation, categorization and in silico analysis of the different ZmHSP families.

Among the plant molecular mechanisms capable of effectively mitigating the effects of adverse weather conditions, the heat shock proteins (HSPs), a group of chaperones with multiple functions, stand out. At a time of full progress on the omic sciences, they look very promising in the genetic engineering field, especially in order to conceive superior genotypes, potentially tolerant to abiotic stresses (AbSts). Recently, some works concerning certain families of maize HSPs (ZmHSPs) were published. However, there was still a lack of a study that, with a high degree of criteria, would fully conglomerate them. Using distinct but complementary strategies, we have prospected as many ZmHSPs candidates as possible, gathering more than a thousand accessions. After detailed data mining, we accounted for 182 validated ones, belonging to seven families, which were subcategorized into classes with potential for functional parity. In them, we identified dozens of motifs with some degree of similarity with proteins from different kingdoms, which may help explain some of their still poorly understood means of action. Through in silico and in vitro approaches, we compared their expression levels after controlled exposure to several AbSts' sources, applied at diverse tissues, on varied phenological stages. Based on gene ontology concepts, we still analyzed them from different perspectives of term enrichment. We have also searched, in model plants and close species, for potentially orthologous genes. With all these new insights, which culminated in a plentiful supplementary material, rich in tables, we aim to constitute a fertile consultation source for those maize researchers attracted by these interesting stress proteins.

Acupuncture modulates the functional connectivity among the subcortical nucleus and fronto-parietal network in adolescents with internet addiction.

BACKGROUND: Internet addiction (IA), recognized as a behavioral addiction, is emerging as a global public health problem. Acupuncture has been demonstrated to be effective in alleviating IA; however, the mechanism is not yet clear. To fill this knowledge gap, our study aimed to investigate the modulatory effects of acupuncture on the functional interactions among the addiction-related networks in adolescents with IA. METHODS: Thirty individuals with IA and thirty age- and sex-matched healthy control subjects (HCs) were recruited. Subjects with IA were given a 40-day acupuncture treatment, and resting-state functional magnetic resonance imaging (fMRI) data were collected before and after acupuncture sessions. HCs received no treatment and underwent one fMRI scan after enrollment. The intergroup differences in functional connectivity (FC) among the subcortical nucleus (SN) and fronto-parietal network (FPN) were compared between HCs and subjects with IA at baseline. Then, the intragroup FC differences between the pre- and post-treatment were analyzed in the IA group. A multiple linear regression model was further employed to fit the FC changes to symptom relief in the IA group. RESULTS: In comparison to HCs, subjects with IA exhibited significantly heightened FC within and between the SN and FPN at baseline. After 40 days of acupuncture treatment, the FC within the FPN and between the SN and FPN were significantly decreased in individuals with IA. Symptom improvement in subjects with IA was well fitted by the decrease in FC between the left midbrain and ventral prefrontal cortex and between the left thalamus and ventral anterior prefrontal cortex. CONCLUSION: These findings confirmed the modulatory effects of acupuncture on the aberrant functional interactions among the SN and FPN, which may partly reflect the neurophysiological mechanism of acupuncture for IA.

Copine-6 is a Ca2+ sensor for activity-induced AMPA receptor exocytosis.

The recruitment of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors underlies the strengthening of neuronal connectivity during learning and memory. This process is triggered by N-methyl-D-aspartate (NMDA) receptor-dependent postsynaptic Ca2+ influx. Synaptotagmin (Syt)-1 and -7 have been proposed as Ca2+ sensors for AMPA receptor exocytosis but are functionally redundant. Here, we identify a cytosolic C2 domain-containing Ca2+-binding protein, Copine-6, that forms a complex with AMPA receptors. Loss of Copine-6 expression impairs activity-induced exocytosis of AMPA receptors in primary neurons, which is rescued by wild-type Copine-6 but not Ca2+-binding mutants. In contrast, Copine-6 loss of function does not affect steady-state expression or tetrodotoxin-induced synaptic upscaling of surface AMPA receptors. Loss of Syt-1/Syt-7 significantly reduces Copine-6 protein expression. Interestingly, overexpression of wild-type Copine-6, but not the Ca2+-binding mutants, restores activity-dependent exocytosis of AMPA receptors in Syt-1/Syt-7 double-knockdown neurons. We conclude that Copine-6 is a postsynaptic Ca2+ sensor that mediates AMPA receptor exocytosis during synaptic potentiation.