Crystal Structure of the Human Cannabinoid Receptor CB1.

Cannabinoid receptor 1 (CB1) is the principal target of Δ9-tetrahydrocannabinol (THC), a psychoactive chemical from Cannabis sativa with a wide range of therapeutic applications and a long history of recreational use. CB1 is activated by endocannabinoids and is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. Here, we present the 2.8 Å crystal structure of human CB1 in complex with AM6538, a stabilizing antagonist, synthesized and characterized for this structural study. The structure of the CB1-AM6538 complex reveals key features of the receptor and critical interactions for antagonist binding. In combination with functional studies and molecular modeling, the structure provides insight into the binding mode of naturally occurring CB1 ligands, such as THC, and synthetic cannabinoids. This enhances our understanding of the molecular basis for the physiological functions of CB1 and provides new opportunities for the design of next-generation CB1-targeting pharmaceuticals.

Uncovering the power of neurofeedback: a meta-analysis of its effectiveness in treating major depressive disorders.

Neurofeedback, a non-invasive intervention, has been increasingly used as a potential treatment for major depressive disorders. However, the effectiveness of neurofeedback in alleviating depressive symptoms remains uncertain. To address this gap, we conducted a comprehensive meta-analysis to evaluate the efficacy of neurofeedback as a treatment for major depressive disorders. We conducted a comprehensive meta-analysis of 22 studies investigating the effects of neurofeedback interventions on depression symptoms, neurophysiological outcomes, and neuropsychological function. Our analysis included the calculation of Hedges' g effect sizes and explored various moderators like intervention settings, study designs, and demographics. Our findings revealed that neurofeedback intervention had a significant impact on depression symptoms (Hedges' g = -0.600) and neurophysiological outcomes (Hedges' g = -0.726). We also observed a moderate effect size for neurofeedback intervention on neuropsychological function (Hedges' g = -0.418). As expected, we observed that longer intervention length was associated with better outcomes for depressive symptoms (ß = -4.36, P < 0.001) and neuropsychological function (ß = -2.89, P = 0.003). Surprisingly, we found that shorter neurofeedback sessions were associated with improvements in neurophysiological outcomes (ß = 3.34, P < 0.001). Our meta-analysis provides compelling evidence that neurofeedback holds promising potential as a non-pharmacological intervention option for effectively improving depressive symptoms, neurophysiological outcomes, and neuropsychological function in individuals with major depressive disorders.

Dync1li1 is required for the survival of mammalian cochlear hair cells by regulating the transportation of autophagosomes.

Dync1li1, a subunit of cytoplasmic dynein 1, is reported to play important roles in intracellular retrograde transport in many tissues. However, the roles of Dync1li1 in the mammalian cochlea remain uninvestigated. Here we first studied the expression pattern of Dync1li1 in the mouse cochlea and found that Dync1li1 is highly expressed in hair cells (HCs) in both neonatal and adult mice cochlea. Next, we used Dync1li1 knockout (KO) mice to investigate its effects on hearing and found that deletion of Dync1li1 leads to early onset of progressive HC loss via apoptosis and to subsequent hearing loss. Further studies revealed that loss of Dync1li1 destabilizes dynein and alters the normal function of dynein. In addition, Dync1li1 KO results in a thinner Golgi apparatus and the accumulation of LC3+ autophagic vacuoles, which triggers HC apoptosis. We also knocked down Dync1li1 in the OC1 cells and found that the number of autophagosomes were significantly increased while the number of autolysosomes were decreased, which suggested that Dync1li1 knockdown leads to impaired transportation of autophagosomes to lysosomes and therefore the accumulation of autophagosomes results in HC apoptosis. Our findings demonstrate that Dync1li1 plays important roles in HC survival through the regulation of autophagosome transportation.

Ionic Current Saturation Enabled by Cation Gating Effect in Metal-Organic-Framework Membranes.

Ion transport through nanoporous two-dimensional (2D) membranes is predicted to be tunable by controlling the charging status of the membranes' planar surfaces, the behavior of which though remains to be assessed experimentally. Here we investigate ion transport through intrinsically porous membranes made of 2D metal-organic-framework layers. In the presence of certain cations, we observe a linear-to-nonlinear transition of the ionic current in response to the applied electric field, the behavior of which is analogous to the cation gating effect in the biological ion channels. Specifically, the ionic currents saturate at transmembrane voltages exceeding a few hundreds of millivolts, depending on the concentration of the gating cations. This is attributed to the binding of cations at the membranes' surfaces, tuning the charging states there and affecting the entry/exit process of translocating ions. Our work also provides 2D membranes as candidates for building nanofluidic devices with tunable transport properties.

Metformin mitigates adipogenesis of fibro-adipogenic progenitors after rotator cuff tears via activating mTOR/ULK1-mediated autophagy.

Muscular fatty infiltration is a common issue after rotator cuff tears (RCTs), which impair shoulder function. Females suffer a higher prevalence and a more severe degree of muscular fatty infiltration after RCT when compared with males, with the underlying mechanisms remaining unclear. Fibro-adipogenic progenitors (FAPs) are the primary source of muscular fatty infiltration following RCT. Our findings disclose that gender-specific disparities in muscular fatty infiltration are linked to mTOR/ULK1-mediated autophagy of FAPs. Decreased autophagic activity contributes to adipogenic differentiation in female FAPs after RCT. Furthermore, metformin could enhance mTOR/ULK1-mediated autophagic processes of FAPs, thereby alleviating fatty infiltration and improving shoulder functionality after RCT. Together, our study reveals that gender differences in muscular fatty infiltration arise from distinct autophagic activities. Metformin could be a promising noninvasive intervention to ameliorate muscular fatty infiltration of RCT.NEW & NOTEWORTHY The current study demonstrated that gender-specific disparities in muscular fatty infiltration are attributed to mTOR/ULK1-mediated autophagy of FAPs. Decreased autophagic activity contributes to adipogenic differentiation in female FAPs after RCT. Moreover, metformin could enhance mTOR/ULK1-mediated autophagic processes of FAPs, thereby alleviating fatty infiltration and improving shoulder functionality after RCT. Therefore, metformin could be a promising noninvasive intervention to ameliorate muscular fatty infiltration of RCT.

LGP2 Promotes Type I Interferon Production To Inhibit PRRSV Infection via Enhancing MDA5-Mediated Signaling.

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens in the global pig industry, which modulates the host's innate antiviral immunity to achieve immune evasion. RIG-I-like receptors (RLRs) sense viral RNA and activate the interferon signaling pathway. LGP2, a member of the RLR family, plays an important role in regulating innate immunity. However, the role of LGP2 in virus infection is controversial. Whether LGP2 has a role during infection with PRRSV remains unclear. Here, we found that LGP2 overexpression restrained the replication of PRRSV, while LGP2 silencing facilitated PRRSV replication. LGP2 was prone to interact with MDA5 and enhanced viral RNA enrichment and recognition by MDA5, thus promoting the activation of RIG-I/IRF3 and NF-κB signaling pathways and reinforcing the expression of proinflammatory cytokines and type I interferon during PRRSV infection. Meanwhile, there was a decreased protein expression of LGP2 upon PRRSV infection in vitro. PRRSV Nsp1 and Nsp2 interacted with LGP2 and promoted K63-linked ubiquitination of LGP2, ultimately leading to the degradation of LGP2. These novel findings indicate that LGP2 plays a role in regulating PRRSV replication through synergistic interaction with MDA5. Moreover, targeting LGP2 is responsible for PRRSV immune evasion. Our work describes a novel mechanism of virus-host interaction and provides the basis for preventing and controlling PRRSV. IMPORTANCE LGP2, a member of retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), shows higher-affinity binding to RNA and work synergism with RIG-I or MDA5. However, LGP2 has divergent responses to different viruses, which remains controversial in antiviral immune responses. Here, we present the detailed process of LGP2 in positively regulating the anti-PRRSV response. Upon PRRSV infection, LGP2 was prone to bind to MDA5 and enhanced MDA5 signaling, manifesting the enrichment of viral RNA on MDA5 and the activation of downstream IRF3 and NF-κB, which results in increased proinflammatory cytokines and type I interferon expression, ultimately inhibiting PRRSV at the early stage of infection. Moreover, PRRSV Nsp1 and Nsp2 interacted with LGP2 via ubiquitin-proteasome pathways, thus blocking LGP2-mediated immune response. This research helps us understand the host recognition and innate antiviral response to PRRSV infection by neglected pattern recognition receptors, which sheds light on the detailed mechanism of virus-host interaction.

The effects of methylphenidate and atomoxetine on Drosophila brain at single-cell resolution and potential drug repurposing for ADHD treatment.

The stimulant methylphenidate (MPH) and the non-stimulant atomoxetine (ATX) are frequently used for the treatment of attention-deficit/hyperactivity disorder (ADHD); however, the function of these drugs in different types of brain cells and their effects on related genes remain largely unknown. To address these questions, we built a pipeline for the simultaneous examination of the activity behavior and transcriptional responses of Drosophila melanogaster at single-cell resolution following drug treatment. We selected the Drosophila with significantly increased locomotor activities (hyperactivity-like behavior) following the administration of each drug in comparison with the control (same food as the drug-treated groups with 5% sucrose, yeast, and blue food dye solution) using EasyFlyTracker. Subsequently, single cell RNA sequencing (scRNASEQ) was used to capture the transcriptome of 82,917 cells, unsupervised clustering analysis of which yielded 28 primary cell clusters representing the major cell types in adult Drosophila brain. Indeed, both neuronal and glial cells responded to MPH and ATX. Further analysis of differentially expressed genes (DEGs) revealed distinct transcriptional changes associated with these two drugs, such as two well-studied dopamine receptor genes (Dop2R and DopEcR) were responsive to MPH but not to ATX at their optimal doses, in addition to genes involved in dopamine metabolism pathways such as Syt1, Sytalpha, Syt7, and Ih in different cell types. More importantly, MPH also suppressed the expression of genes encoding other neurotransmitter receptors and synaptic signaling molecules in many cell types, especially those for Glu and GABA, while the responsive effects of ATX were much weaker. In addition to monoaminergic neuronal transmitters, other neurotransmitters have also shown a similar pattern with respect to a stronger effect associated with MPH than with ATX. Moreover, we identified four distinct glial cell subtypes responsive to the two drugs and detected a greater number of differentially expressed genes associated with ensheathing and astrocyte-like glia. Furthermore, our study provides a rich resource of candidate target genes, supported by drug set enrichment analysis (P = 2.10E-4; hypergeometric test), for the further exploration of drug repurposing. The whole list of candidates can be found at ADHDrug ( http://adhdrug.cibr.ac.cn/ ). In conclusion, we propose a fast and cost-efficient pipeline to explore the underlying molecular mechanisms of ADHD drug treatment in Drosophila brain at single-cell resolution, which may further facilitate drug repurposing applications.

Fe-Doped SrCoOx FET Sensors for Extreme Alkaline pH Sensing.

The accurate measurement of pH in highly alkaline environments is critical for various industrial applications but remains a complex task. This paper discusses the development of novel Fe-doped SrCoOx-based FET sensors for the detection of extreme alkaline pH levels. Through a comprehensive investigation of the effects of Fe doping on the structure, electrical properties, and sensing performance of SrCoOx, we have identified the optimal doping level that significantly enhances the sensor's performance in highly alkaline conditions. With a Fe doping level of 5 mol %, the sensitivity of the sensor improves to 0.86 lg(Ω)/pH while maintaining the response rate. Further increasing the Fe doping to 10 mol % results in a sensor that demonstrates favorable response time, a suitable pH range, and a linear correlation between lg(R) and pH. The combination of X-ray photoelectron spectroscopy and X-ray diffraction analysis provides insight into the regulation mechanisms of Fe doping on the crystal structure, electronic structure, and oxygen vacancy concentration of SrCoOx. Our findings indicate that Fe doping leads to an increase in oxygen vacancy concentration and a decrease in the energy barrier for oxygen ion migration, which contributes to the improved sensing performance of the Fe-doped SrCoOx sensors. Additionally, the study highlights the influence of oxygen vacancy concentration on the electrical properties of SrCoOx. Precise control over the concentration of oxygen vacancies is crucial for optimizing the sensitivity and response speed of SrCoOx FET sensors under extreme alkalinity conditions.

Measuring coefficient of thermal expansion of materials of micrometre size using SEM/FIB microscope with in situ MEMS heating stage.

A new method is proposed to measure the linear coefficient of thermal expansion (CTE) of solid metals and ceramics of micron-sized dimensions. This approach uses a focused ion beam (FIB) to extract and transfer a slab of the sample, typically (15-20) ×10 × (3-5) µm onto a Micro-Electro-Mechanical Systems (MEMS) in situ heating holder inside a scanning electron microscope (SEM). CTE is thereafter calculated by image correlating the change of length (ΔL) between the fiducial marks on the slab as a function of temperature, taking advantage of the temperature calibration of the MEMS heating holder and nanometre resolution of the scanning electron microscope. The CTE results are validated to be consistent with standard copper and silicon. We further demonstrate the method on a graphene platelet reinforced copper composite and a graphite filler phase isolated from a bulk sample, these represent materials that cannot be practically synthesised or isolated at the macro-scale. Errors associated with the measurement are discussed.

Predicting long-term outcomes in patients with classical trigeminal neuralgia following microvascular decompression with an MRI-based radiomics nomogram: a multicentre study.

OBJECTIVES: This study aimed to develop a clinical-radiomics nomogram to predict the long-term outcomes of patients with classical trigeminal neuralgia (CTN) following microvascular decompression (MVD). MATERIALS AND METHODS: This retrospective study included 455 patients with CTN who underwent MVD from three independent institutions A total of 2030 radiomics features from the cistern segment of the trigeminal nerve were extracted computationally from the three-dimensional steady-state free precession and three-dimensional time-of-flight magnetic resonance angiography sequences. Using the least absolute shrinkage and selection operator regression, 16 features were chosen to develop radiomics signatures. A clinical-radiomics nomogram was subsequently developed in the development cohort of 279 patients via multivariate Cox regression. The predictive performance and clinical application of the nomogram were assessed in an external cohort consisting of 176 patients. RESULTS: Sixteen highly outcome-related radiomics features extracted from multisequence images were used to construct the radiomics model, with concordance indices (C-index) of 0.804 and 0.796 in the development and test cohorts, respectively. Additionally, a clinical-radiomics nomogram was developed by incorporating both radiomics features and clinical characteristics (i.e., pain type and degree of neurovascular compression) and yielded higher C-indices of 0.865 and 0.834 in the development and test cohorts, respectively. K‒M survival analysis indicated that the nomogram successfully stratified patients with CTN into high-risk and low-risk groups for poor outcomes (hazard ratio: 37.18, p < 0.001). CONCLUSION: Our study findings indicated that the clinical-radiomics nomogram exhibited promising performance in accurately predicting long-term pain outcomes following MVD. CLINICAL RELEVANCE STATEMENT: This model had the potential to aid clinicians in making well-informed decisions regarding the treatment of patients with CTN. KEY POINTS: Trigeminal neuralgia recurs in about one-third of patients after undergoing MVD. The clinical-radiomics nomogram stratified patients into high- and low-risk groups for poor surgical outcomes. Using this nomogram could better inform patients of recurrence risk and allow for discussion of alternative treatments.

Synthesis of acridones via Ir(III)-catalyzed amination annulation of oxazoles with anthranils.

An unprecedented Ir(III)-catalyzed C-H activation/amination/annulation of 2-phenyloxazoles with anthranils for the highly selective preparation of acridone derivatives in one-pot under controlled conditions is reported. This protocol is characterized by atom economy and high regioselectivity. A wide range of anthranils with 2-phenyloxazoles were well tolerated and afforded the desired products in moderate to good yields, in which the anthranil serves as a convenient amination reagent.

Transparent grating-based metamaterials for dynamic infrared radiative regulation smart windows.

Dynamic infrared radiation regulation has been widely explored for smart windows because of its vital importance for comfortable and energy-efficient buildings. However, it remains a great challenge to synchronously achieve high visible transmittance and pronounced infrared tunability. Here, we propose a dynamic infrared tunable metamaterial composed of indium tin oxide (ITO) gratings, an air insulator, and an ITO reflector. The ITO grating-based infrared radiation regulator exhibits a high emissivity tunability of 0.73 at 8-13 µm while maintaining a high visible transmittance of 0.65 and 0.72 before and after actuation, respectively. By adjusting the geometric parameters, the tunable bandwidth can be further extended to 3-30 µm and the ultra-broadband tunability reaches 0.62. The excellent infrared tunable performance arises from the insulator thickness-dependent effect of Fabry-Pérot and propagating surface plasmon resonance coupling and decoupling, which lead to perfect and low absorption, respectively. This work provides potential for the advancement of smart window technology and makes a significant contribution to sustainable buildings.

Bone marrow mesenchymal stem cells-derived exosomes ameliorate LPS-induced acute lung injury by miR-223-regulated alveolar macrophage M2 polarization.

Numerous studies have shown that the M2 polarization of alveolar macrophages (AM) plays a protective role in acute lung injury (ALI). Mesenchymal stem cells (MSCs) secreted exosomes have been reported to be involved in inflammatory diseases by the effects of polarized M1/M2 macrophage populations. However, whether bone marrow mesenchymal stem cells (BMMSCs) derived exosomes could protect from ALI and its mechanisms are still unclear. Here, we explored the role of exosomes from BMMSC in rat AM polarization and the lipopolysaccharide- (LPS-) induced ALI rat model. Furthermore, the levels of exosomal miR-223 in BMMSCs were measured by RT-qPCR. Additionally, miR-223 mimics and its inhibitors were used to verify the vital role of miR-223 of BMMSCs-derived exosomes in the polarization of M2 macrophages. The results showed that BMMSCs-derived exosomes were taken up by the AM. Exosomes derived from BMMSCs promoted M2 polarization of AM in vitro. BMMSCs exosomes effectively mitigated pathological injuries, lung edema, and the inflammation of rats from LPS-induced ALI, accompanied by an increase of M2 polarization of AM in lung tissue. Interestingly, we also found that miR-223 was enriched in BMMSCs-derived exosomes, and overexpression of miR-223 in BMMSCs-derived exosomes promoted M2 polarization of AM while depressing miR-223 showed opposite effects in AM. The present study demonstrated that BMMSCs-derived exosomes triggered alveolar M2 polarization to improve inflammation by transferring miR-223, which may provide new therapeutic strategies in ALI.

Biologically active isoquinoline alkaloids covering 2019-2022.

Isoquinoline alkaloids are an important class of natural products that are abundant in the plant kingdom and exhibit a wide range of structural diversity and biological activities. With the deepening of research in recent years, more and more isoquinoline alkaloids have been isolated and identified and proved to contain a variety of biological activities and pharmacological effects. In this review, we introduce the research progress of isoquinoline alkaloids from 2019 to 2022, mainly in the part of biological activities, including antitumor, antimicrobial, antidiabetic, antiviral, anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, analgesic, and other activities. This study provides a clear direction for the rational development and utilization of isoquinoline alkaloids, suggesting that these alkaloids have great potential in the field of drug research.

Label-free cell phenotypic profiling of histamine H4R receptor and discovery of non-competitive H4R antagonist from natural products.

Histamine 4 receptor (H4R), the most recently identified subtype of histamine receptor, primarily induces inflammatory reactions upon activation. Several H4R antagonists have been developed for the treatment of inflammatory bowel disease (IBD) and atopic dermatitis (AD), but their use has been limited by adverse side effects, such as a short half-life and toxicity. Natural products, as an important source of anti-inflammatory agents, offer minimal side effects and reduced toxicity. This work aimed to identify novel H4R antagonists from natural products. An H4R target-pathway model deconvoluted downstream Gi and MAPK signaling pathways was established utilizing cellular label-free integrative pharmacology (CLIP), on which 148 natural products were screened. Cryptotanshinone was identified as selective H4R antagonist, with an IC50 value of 11.68 ± 1.30 µM, which was verified with Fluorescence Imaging Plate Reader (FLIPR) and Cellular Thermal Shift (CTS) assays. The kinetic binding profile revealed the noncompetitive antagonistic property of cryptotanshinone. Two allosteric binding sites of H4R were predicted using SiteMap, Fpocket and CavityPlus. Subsequent molecular docking and dynamics simulation indicated that cryptotanshinone interacts with H4R at a pocket formed by the outward interfaces between TM3/4/5, potentially representing a new allosteric binding site for H4R. Overall, this study introduced cryptotanshinone as a novel H4R antagonist, offering promise as a new hit for drug design of H4R antagonist. Additionally, this study provided a novel screening model for the discovery of H4R antagonists.

Dampened motivation in schizophrenia: evidence from a novel effort-based decision-making task in social scenarios.

Apathy represents a significant manifestation of negative symptoms within individuals diagnosed with schizophrenia (SCZ) and exerts a profound impact on their social relationships. However, the specific implications of this motivational deficit in social scenarios have yet to be fully elucidated. The present study aimed to examine effort-based decision-making in social scenarios and its relation to apathy symptoms in SCZ patients. We initially recruited a group of 50 healthy participants (16 males) to assess the validity of the paradigm. Subsequently, we recruited 45 individuals diagnosed with SCZ (24 males) and 49 demographically-matched healthy controls (HC, 25 males) for the main study. The Mock Job Interview Task was developed to measure effort-based decision-making in social scenarios. The proportion of hard-task choice and a range of subjective ratings were obtained to examine potential between-group differences. SCZ patients were less likely than HC to choose the hard task with strict interviewers, and this group difference was significant when the hard-task reward value was medium and high. More severe apathy symptoms were significantly correlated with an overall reduced likelihood of making a hard-task choice. When dividing the jobs into two categories based on the levels of social engagement needed, SCZ patients were less willing to expend effort to pursue a potential offer for jobs requiring higher social engagement. Our findings indicated impaired effort-based decision-making in SCZ can be generalized from the monetary/nonsocial to a more ecologically social dimension. Our findings affirm the critical role of aberrant effort allocation on negative symptoms, and may facilitate the development of targeted clinical interventions.

Assessing immunogenicity of CRISPR-NCas9 engineered strain against porcine epidemic diarrhea virus.

Porcine epidemic diarrhea (PED) caused by porcine epidemic diarrhea virus (PEDV), is an acute and highly infectious disease, resulting in substantial economic losses in the pig industry. Given that PEDV primarily infects the mucosal surfaces of the intestinal tract, it is crucial to improve the mucosal immunity to prevent viral invasion. Lactic acid bacteria (LAB) oral vaccines offer unique advantages and potential applications in combatting mucosal infectious diseases, making them an ideal approach for controlling PED outbreaks. However, traditional LAB oral vaccines use plasmids for exogenous protein expression and antibiotic genes as selection markers. Antibiotic genes can be diffused through transposition, transfer, or homologous recombination, resulting in the generation of drug-resistant strains. To overcome these issues, genome-editing technology has been developed to achieve gene expression in LAB genomes. In this study, we used the CRISPR-NCas9 system to integrate the PEDV S1 gene into the genome of alanine racemase-deficient Lactobacillus paracasei △Alr HLJ-27 (L. paracasei △Alr HLJ-27) at the thymidylate synthase (thyA) site, generating a strain, S1/△Alr HLJ-27. We conducted immunization assays in mice and piglets to evaluate the level of immune response and evaluated its protective effect against PEDV through challenge tests in piglets. Oral administration of the strain S1/△Alr HLJ-27 in mice and piglets elicited mucosal, humoral, and cellular immune responses. The strain also exhibited a certain level of resistance against PEDV infection in piglets. These results demonstrate the potential of S1/△Alr HLJ-27 as an oral vaccine candidate for PEDV control. KEY POINTS: • A strain S1/△Alr HLJ-27 was constructed as the candidate for an oral vaccine. • Immunogenicity response and challenge test was carried out to analyze the ability of the strain. • The strain S1/△Alr HLJ-27 could provide protection for piglets to a certain extent.

Artificial intelligence assistance for fetal development: evaluation of an automated software for biometry measurements in the mid-trimester.

BACKGROUND: This study presents CUPID, an advanced automated measurement software based on Artificial Intelligence (AI), designed to evaluate nine fetal biometric parameters in the mid-trimester. Our primary objective was to assess and compare the CUPID performance of experienced senior and junior radiologists. MATERIALS AND METHODS: This prospective cross-sectional study was conducted at Shenzhen University General Hospital between September 2022 and June 2023, and focused on mid-trimester fetuses. All ultrasound images of the six standard planes, that enabled the evaluation of nine biometric measurements, were included to compare the performance of CUPID through subjective and objective assessments. RESULTS: There were 642 fetuses with a mean (±SD) age of 22 ± 2.82 weeks at enrollment. In the subjective quality assessment, out of 642 images representing nine biometric measurements, 617-635 images (90.65-96.11%) of CUPID caliper placements were determined to be accurately placed and did not require any adjustments. Whereas, for the junior category, 447-691 images (69.63-92.06%) were determined to be accurately placed and did not require any adjustments. In the objective measurement indicators, across all nine biometric parameters and estimated fetal weight (EFW), the intra-class correlation coefficients (ICC) (0.843-0.990) and Pearson correlation coefficients (PCC) (0.765-0.978) between the senior radiologist and CUPID reflected good reliability compared with the ICC (0.306-0.937) and PCC (0.566-0.947) between the senior and junior radiologists. Additionally, the mean absolute error (MAE), percentage error (PE), and average error in days of gestation were lower between the senior and CUPID compared to the difference between the senior and junior radiologists. The specific differences are as follows: MAE (0.36-2.53 mm, 14.67 g) compared to (0.64- 8.13 mm, 38.05 g), PE (0.94-9.38%) compared to (1.58-16.04%), and average error in days (3.99-7.92 days) compared to (4.35-11.06 days). In the time-consuming task, CUPID only takes 0.05-0.07 s to measure nine biometric parameters, while senior and junior radiologists require 4.79-11.68 s and 4.95-13.44 s, respectively. CONCLUSIONS: CUPID has proven to be highly accurate and efficient software for automatically measuring fetal biometry, gestational age, and fetal weight, providing a precise and fast tool for assessing fetal growth and development.

Unraveling the link between childhood maltreatment and depression: Insights from the role of ventral striatum and middle cingulate cortex in hedonic experience and emotion regulation.

Childhood maltreatment is an established risk factor for psychopathology. However, it remains unclear how childhood traumatic events relate to mental health problems and how the brain is involved. This study examined the serial mediation effect of brain morphological alterations and emotion-/reward-related functions on linking the relationship from maltreatment to depression. We recruited 156 healthy adolescents and young adults and an additional sample of 31 adolescents with major depressive disorder for assessment of childhood maltreatment, depressive symptoms, cognitive reappraisal and anticipatory/consummatory pleasure. Structural MRI data were acquired to identify maltreatment-related cortical and subcortical morphological differences. The mediation models suggested that emotional maltreatment of abuse and neglect, was respectively associated with increased gray matter volume in the ventral striatum and greater thickness in the middle cingulate cortex. These structural alterations were further related to reduced anticipatory pleasure and disrupted cognitive reappraisal, which contributed to more severe depressive symptoms among healthy individuals. The above mediating effects were not replicated in our clinical group partly due to the small sample size. Preventative interventions can target emotional and reward systems to foster resilience and reduce the likelihood of future psychiatric disorders among individuals with a history of maltreatment.

RECENT TRENDS IN THE CUMULATIVE INCIDENCE AND INTERVENTION PATTERNS OF RETINOPATHY OF PREMATURITY IN JAPAN: A Multicenter Analysis, 2011-2020.

PURPOSE: To investigate recent trends in the cumulative incidence and treatment patterns of retinopathy of prematurity (ROP) in Japan. METHODS: A retrospective multicenter cohort was conducted from 2011 to 2020 using the Diagnosis Procedure Combination inpatient database. Preterm newborns with birth weight <2,500 g were categorized by birth weight. The cumulative incidence of ROP, treatment patterns, and association between treatment and birth weight were investigated. RESULTS: A total of 82,683 preterm infants were identified, of whom 9,335 (11.3%) were diagnosed with ROP. The cumulative incidence of ROP increased by 15% in those with birth weight <500 g over the study period. Among the ROP infants, 20.2% received treatment, including laser photocoagulation (94.8%), intravitreal injection (3.8%), or both (1.8%). The proportion receiving laser photocoagulation decreased followed by an increase in intravitreal injection. This shift in intervention pattern was most conspicuous for those with birth weight 750 to 1,249 g. The risk ratio of receiving laser and intravitreal injection for those weighing <500 g was 24.7 (95% confidence interval, 10.5-58.2) and 28.4 (5.8-138.1), respectively, as compared with infants weighing >1,500 g. CONCLUSION: The cumulative incidence of ROP increased in infants with birth weight <500 g. A shift from laser photocoagulation to intravitreal injection was observed in the more recent years.