Enhancement of motor functional recovery in thoracic spinal cord injury: voluntary wheel running versus forced treadmill exercise.

JOURNAL/nrgr/04.03/01300535-202503000-00028/figure1/v/2024-06-17T092413Z/r/image-tiff Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group (10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

Formation of self-assembled fibril aggregates of trypsin-controllably hydrolyzed soy protein and its regulation on stability of high internal phase Pickering emulsions.

The mechanisms of trypsin hydrolysis time on the structure of soy protein hydrolysate fibril aggregates (SPHFAs) and the stability of SPHFAs-high internal phase Pickering emulsions (HIPPEs) were investigated. SPHFAs were prepared using soy protein hydrolysate (SPH) with different trypsin hydrolysis time (0 min-120 min) to stabilize SPHFAs-HIPPEs. The results showed that moderate trypsin hydrolysis (30 min, hydrolysis degree of 2.31 %) induced SPH unfolding and increased the surface hydrophobicity of SPH, thereby promoting the formation of flexible SPHFAs with maximal thioflavin T intensity and ζ-potential. Moreover, moderate trypsin hydrolysis improved the viscoelasticity of SPHFAs-HIPPEs, and SPHFAs-HIPPEs remained stable after storage at 25 °C for 80 d and heating at 100 °C for 1 h. Excessive trypsin hydrolysis (> 30 min) decreased the stability of SPHFAs-HIPPEs. In conclusion, moderate trypsin hydrolysis promoted the formation of flexible SPHFAs with high surface charge by inducing SPH unfolding, thereby promoting the stability of SPHFAs-HIPPEs.

Molecularly imprinted polymer based on covalent organic framework coated steel substrate as the mass spectrometric ionization source for the direct detect of aflatoxins in complex food matrices.

Ambient mass spectrometry allows direct analysis of various sample types with minimal or no pretreatment. However, due to the influence of matrix effects, there are sensitivity and issues in analyzing trace analytes in complex food samples. In this work, we developed a spray mass spectrometry platform based on SSS@TPBD-TPA@MIPs (Stainless steel substrate (SSS), terephthalaldehyde (TPA), N, N, N', N'-tetrakis(p-aminophenyl)-p-phenylenediamine (TPBD), molecularly imprinted polymer (MIP)), for rapid, in situ, high-throughput, highly enrichment efficiency and highly selective trace analysis of aflatoxins. By simplifying the sample pretreatment and directly applying high voltage for ESI-MS, the analysis can be completed within 1 min. The established method base on SSS@TPBD-TPA@MIPs exhibited high sensitivity and accuracy when determine trace level AFs in maize and peanuts. The results demonstrated a good linear relationship within the range of 0.01-10 µg/L, with the determination coefficient (R2) ≥ 0.9956. The limits of detection (LODs) was 0.035-0.3 ng/mL and limits of quantitation (LOQs) was 0.12-0.99 ng/mL, with acceptable recovery rate of 82.09-115.66 % and good repeatability represented by the relative standard deviation (RSD) less than 17.43 %. Furthermore, SSS@TPBD-TPA@MIPs exhibited excellent reusability, with more than 8 repeated uses, and showed good adsorption performance.

Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202505000-00029/figure1/v/2024-07-28T173839Z/r/image-tiff Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties. A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury. A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity, and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar, thus limiting axonal reentry into the host spinal cord. Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury. We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders, Schwann cells migrated for considerable distances in both rostral and caudal directions. Such Schwann cell migration led to enhanced axonal regrowth, including the serotonergic and dopaminergic axons originating from supraspinal regions, and promoted recovery of locomotor and urinary bladder functions. Importantly, the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury, even when treatment was delayed for 3 months to mimic chronic spinal cord injury. These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

Synthesis, Properties, and Biocompatibility of 4-Carboxyphenyboronic Acid-Modified Gelatin-Methacryloyl: A Hydrogel for Retinal Surgeries.

The current surgical adjunctive for vitreoretinal surgeries fails to provide an adequate 3D structure for cellular regeneration. A one-pot synthesis of gelatin-methacryloyl (GelMA) followed by modification with 4-carboxyphenylboronic acid (4-CPBA) was performed to fabricate 4-CPBA-modified GelMA (4CPBA@GelMA), a gelatin-based hydrogel. 4CPBA@GelMA was photo-cross-linked by 405 nm violet light and examined using nuclear magnetic resonance (NMR), Fourier-transform infrared spectrometry (FTIR), scanning electron microscopy (SEM), and rheometry. In vitro biocompatibility was examined by Müller cell proliferation assays exposed to 4CPBA@GelMA and violet light. In vivo retinal biocompatibility was evaluated by electroretinography of rat eyes that were exposed to intravitreally injected and photo-cross-linked 4CPBA@GelMA at days 3, 7, 14, and 28 post-injection. Following electroretinography, histology and immunohistochemistry were performed on the retinas. The NMR results indicated amidation of GelMA by 4-CPBA, and FTIR confirmed the presence of the CPBA ring in 4CPBA@GelMA samples. SEM revealed that 4CPBA@GelMA had significantly larger pores than GelMA (56.9 ± 9.5 vs 35.1 ± 2.8 µm; P < 0.001). Rheological findings showed that, unlike GelMA and gelatin, 4CPBA@GelMA has Newtonian fluid properties at room temperature. Exposure to 4CPBA@GelMA did not significantly affect Müller cell viability in a proliferation assay; moreover, electroretinography findings indicated normal waveforms and implicit times, and histology and immunohistochemistry examinations revealed no significant changes. In this study, we established the high retinal compatibility of 4CPBA@GelMA. The low viscosity of 4CPBA@GelMA is ideal for injection via small-gauge needles, and the larger pore size and three-dimensional network both potentiate cellular migration and growth. These features made 4CPBA@GelMA a candidate for vitreoretinal surgical adjunctive that might promote retinal regeneration.

Effects of decision making and impulsivity on the addictive features of non-suicidal self-injury behaviors in adolescents with depressive disorder.

BACKGROUND: Non-suicidal self-injury (NSSI) behaviors pose a significant threat to the physical and psychological well-being of adolescents. Recent research suggests that persistent, uncontrollable and repetitive NSSI can be conceptualized as a behavioral addiction. The addictive feature of NSSI behavior can be assessed using Ottawa self-injury inventory (OSI), the higher addiction score indicates the more serious NSSI behavior. This study aims to explore the relationship of impulsivity and decision-making on the addictive features of NSSI in adolescents with depressive disorder, to explore the influencing factors of behavioral addictive features of NSSI and to predict the addictive features of NSSI. METHODS: Using a cross-sectional design, a total of 126 adolescent outpatients and inpatients with a mean age of 15.49 years old (M = 15.49, SD = 1.56), male students (n = 28, 22.2%) and female students (n = 98, 77.8%) diagnosed with depressive disorders were recruited according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and clinical interviews were completed by two psychiatrists. NSSI addictive features according to the OSI's addictive features items. The final group was categorized into three groups: depression without NSSI (n = 42), depression with NSSI without addictive features (n = 44), and depression with NSSI and addictive features (n = 40). The present study employed the Hamilton Depression Scale (HAMD-24), Chinese Revised Barratt Impulsiveness Scale Version 11 (BIS-11), OSI, and the Adolescent Non-Suicidal Self-Injury Questionnaire (ANSSIQ). Cognitive decision-making abilities were assessed using the Iowa Gambling Task (IGT). RESULTS: The depression with NSSI addictive features group had significantly lower total net scores and net scores of block3, block4, and block5 in the IGT than the depression without NSSI group, whereas there was no statistically significant difference between the two in net scores of block1 and block2. Lower scores mean more unfavorable decisions and strategy adjustments. The addictive features of NSSI behaviors were significantly and positively correlated with the severity of NSSI behaviors, depression, and cognitive impulsiveness, and significantly and negatively correlated with the total net score of the IGT. The severity of NSSI behaviors, severity of depression, cognitive impulsiveness positively predicts the addictive features of NSSI behaviors, the total net score of the IGT negatively predicted the addictive features of NSSI behaviors. CONCLUSION: Adolescents with depressive disorders with NSSI behavioral addictive features had higher severity of depression, exhibited higher cognitive impulsivity, and made more unfavorable decisions when making choices.

Tofacitinib treatment for plaque psoriasis and psoriatic arthritis: A meta-analysis of randomised controlled trials.

Objectives Tofacitinib is used as an oral Janus-associated kinase (JAK) inhibitor acting on JAK1 and JAK3, in treating psoriatic disease. However, there is still no consensus on the optimal dosage and duration of tofacitinib. In this study, we aimed to evaluate the effects of tofacitinib in treating psoriatic disease. Methods and Materials A literature search was done utilising Cochrane library, Medline, EMBASE, Wiley Online library, Web of Science and BIOSIS Previews through December 18, 2022. We performed a meta-analysis of published original studies to assess the impact of tofacitinib in plaque psoriasis or psoriatic arthritis therapy based on seven randomised controlled trials (RCTs) involving 2,672 patients (receiving tofacitinib) and 853 controls (receiving placebo). Results Compared with placebo, the treatment of 5 mg twice-daily (BID) tofacitinib for 12 weeks is sufficient to significantly alleviate the main clinical manifestations of psoriasis [≥75% decrease in Psoriasis Area and Severity Index score (PASI 75): Risk ratio (RR)=4.38 (95% Confidence interval (CI) 2.51 to 7.64); ≥90% decrease in PASI score (PASI 90): RR=21.68 (95% CI 4.20 to 111.85); Physician's Global Assessment of 'clear' or 'almost clear' (PGA 0/1): RR=3.93 (95%CI 3.03 to 5.09)]. Interestingly, there was no significant difference in improvement in PGA 0/1 with 5 mg BID tofacitinib given for 16 weeks when compared with 5 mg BID tofacitinib for 12 weeks [RR=1.11 (95%CI 0.98 to 1.25)]. Additionally, the 5 mg BID tofacitinib for 16 weeks treatment schedule significantly increased the incidence of upper respiratory tract infection (URTI) [RR=1.89 (95%CI 1.06 to 3.38)] as compared to 5 mg BID tofacitinib for 12 weeks treatment schedule [RR=1.15 (95%CI 0.60 to 2.20)]. Conclusion The 5 mg BID tofacitinib for 12 weeks treatment significantly improved psoriasis without causing too many specific adverse events. This indicated that tofacitinib is an effective treatment plan for psoriatic disease by reasonably controlling dosage and dosing time.

Pathologic Response of Phase III Study: Perioperative Camrelizumab Plus Rivoceranib and Chemotherapy Versus Chemotherapy for Locally Advanced Gastric Cancer (DRAGON IV/CAP 05).

PURPOSE: This multicenter, randomized phase III trial evaluated the efficacy and safety of perioperative camrelizumab (an anti-PD-1 antibody) plus low-dose rivoceranib (a VEGFR-2 inhibitor) and S-1 and oxaliplatin (SOX) (SOXRC), high-dose rivoceranib plus SOX (SOXR), and SOX alone (SOX) for locally advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. METHODS: Patients with T3-4aN + M0 G/GEJ adenocarcinoma were randomly assigned (1:1:1) to receive perioperative treatment with SOXRC, SOXR, or SOX. The primary end points were pathologic complete response (pCR) and event-free survival. The Independent Data Monitoring Committee recommended stopping enrollment in the SOXR group on the basis of the safety data of the first 103 randomly assigned patients in the three groups. The patients were then randomly assigned 1:1 to the SOXRC or SOX groups. This report presents the pCR results obtained per protocol for the first 360 randomly assigned patients who had the opportunity for surgery in the SOXRC and SOX groups. RESULTS: In the SOXRC and SOX groups, of the 180 patients in each group, 99% and 98% of patients received neoadjuvant therapy, 91% and 94% completed planned neoadjuvant therapy, and 86% and 87% underwent surgery, respectively. The pCR was significantly higher in the SOXRC group at 18.3% (95% CI, 13.0 to 24.8) compared with 5.0% (95% CI, 2.3 to 9.3) in the SOX group (difference of 13.7%; 95% CI, 7.2 to 20.1; odds ratio of 4.5 [95% CI, 2.1 to 9.9]). The one-sided P value was <.0001, crossing the prespecified statistical significance threshold of P = .005. Surgical complications and grade ≥3 neoadjuvant treatment-related adverse events were 27% versus 33% and 34% versus 17% for SOXRC and SOX, respectively. CONCLUSION: The SOXRC regimen significantly improved pCR compared with SOX alone in patients with G/GEJ adenocarcinoma with a tolerable safety profile.

The Pharmacokinetics and Liver-Targeting Evaluation of Silybin Liposomes Mediated by the NTCP/OCTN2 Dual Receptors.

The disadvantage of a traditional dosage regimen is the inability to deliver a sufficient drug concentration to the lesion site, which can result in adverse side effects due to nonspecific drug delivery. Actively targeting hepatic cells is a promising therapeutic strategy for liver disease. In this study, l-carnitine and a targeting peptide derived from the hepatitis B virus large envelope protein were used to modify liposomes for drug delivery to the liver through the sodium taurocholate cotransporting polypeptide (NTCP) and the organic cation/carnitine transporter 2 (OCTN2) receptors. Silybin was selected as the model drug. The solubility of silybin can reach 0.3 mg/mL after encapsulation in liposomes. The NTCP-specific and OCTN2-accelerated Myrcludex B and l-carnitine dual-modified liposomes were validated in vitro. The uptake of coumarin-6 in dual ligand-modified liposomes by hepatocytes was up to 2.36 µg/mg compared with unmodified liposomes (1.05 µg/mg). The pharmacokinetics and targeting abilities of various liposome formulations were evaluated in Kunming mice. Targeted liposomes increased the concentration of silybin and prolonged the drug's retention time in the liver. The area under the liver's pharmacokinetic curve of targeted liposomes was twice that of silybin injection, suggesting the promising application potential of silybin-loaded hepatotropic nanovesicles.

VGLL3 modulates chemosensitivity through promoting DNA double-strand break repair.

Transcription cofactor vestigial-like 3 (VGLL3), as a master regulator of female-biased autoimmunity, also functions in tumor development, while the underlying mechanisms remain largely elusive. Here, we report that VGLL3 plays an important role in DNA damage response (DDR). VGLL3 can be recruited to damage sites in a PARylation-dependent manner. VGLL3 depletion impairs the accumulation of RNF8 and RAD51 at sites of DNA damage, leading to reduced homologous recombination efficiency and increased cellular sensitivity to chemotherapeutic drugs. Mechanistically, VGLL3 can prevent CtIP from KLHL15-mediated ubiquitination and degradation through competitive binding with KLHL15 and, meanwhile, stabilize MDC1 by limiting TRIP12-MDC1 but promoting USP7-MDC1 associations for optimal RNF8 signaling initiation. Consistently, VGLL3 depletion delays tumor development and sensitizes the xenografts to etoposide treatment. Overall, our results reveal an unexpected role of VGLL3 in DDR, which is distinct from its transcriptional cofactor function and not conserved among VGLL family members.

Using artificial intelligence to document the hidden RNA virosphere.

Current metagenomic tools can fail to identify highly divergent RNA viruses. We developed a deep learning algorithm, termed LucaProt, to discover highly divergent RNA-dependent RNA polymerase (RdRP) sequences in 10,487 metatranscriptomes generated from diverse global ecosystems. LucaProt integrates both sequence and predicted structural information, enabling the accurate detection of RdRP sequences. Using this approach, we identified 161,979 potential RNA virus species and 180 RNA virus supergroups, including many previously poorly studied groups, as well as RNA virus genomes of exceptional length (up to 47,250 nucleotides) and genomic complexity. A subset of these novel RNA viruses was confirmed by RT-PCR and RNA/DNA sequencing. Newly discovered RNA viruses were present in diverse environments, including air, hot springs, and hydrothermal vents, with virus diversity and abundance varying substantially among ecosystems. This study advances virus discovery, highlights the scale of the virosphere, and provides computational tools to better document the global RNA virome.

Evaluation of immune checkpoint inhibitors for colorectal cancer: A network meta­analysis.

Colorectal cancer (CRC) is challenging to treat due to its high metastatic rate. Recent strategies have focused on combining immune checkpoint inhibitors (ICIs) with other treatments. The aim of the present study was to conduct a network meta-analysis of randomized controlled trials (RCTs) to assess the efficacy and adverse effects of different ICI treatments for CRC. A literature search for RCTs was conducted using PubMed, the Cochrane Library, Embase, ClinicalTrials.gov and Web of Science databases, covering the period from the inception of each database until April 2024. A total of 12 RCTs involving 2,050 participants were selected for inclusion in the analysis. The network meta-analysis employed the MetaInsight tool to assess multiple endpoints. The criteria for study selection were based on the Population, Intervention, Comparison, Outcome and Studies framework as follows: i) Population, patients with CRC; ii) intervention, studies using ICI to treat CRC; iii) comparison, active comparators, including placebo; iv) outcome, overall survival, progression-free survival, objective response rate and adverse events; and v) study design, RCTs. The results of the analysis revealed that programmed cell death-ligand 1 (PD-L1) inhibitors significantly improved overall survival time [mean difference (MD), 2.28 months; 95% confidence interval (CI), 0.44 to 4.11], while programmed cell death protein 1 (PD-1) inhibitors exhibited a superior progression-free survival time (MD, 4.79 months; 95% CI, 3.18 to 6.40) compared with active comparators. However, none of the ICI treatments had significant differences in odds ratios for the objective response rate and adverse events compared with active comparators. These findings indicate that treatment with PD-L1 and PD-1 inhibitors improved the overall survival time and delayed disease progression in patients with CRC. These findings offer valuable insights for future research aimed at improving CRC patient outcomes.

Targeted apoptosis of senescent cells by valproic acid alleviates therapy-induced cellular senescence and lung aging.

BACKGROUND: Accumulation of senescent cells in tissues and their downstream effect programs have emerged as key drivers of aging and age-associated pathologies. Recent progresses in senotherapeutics indicated that either selectively killing senescent cells with senolytics or suppressing the senescence-associated secretory phenotype (SASP) secretion using senomorphics contributes to extending of the healthy lifespan and alleviating numerous age-related disorders in mice. PURPOSE: However, the potential side-effects and long-term cytotoxicity of the above novel compounds have not yet been determined. Therefore, it seems to be more efficient to explore new senotherapeutical functions from approved drugs. METHODS: The effects of valproic acid (VPA), a derivative of valine, in cellular senescence were evaluated by senescence-associated ß galactosidase (SA-ß-Gal) staining, flow cytometry and western blot (WB). The cell viability was tested using CCK-8 kits. Cell apoptosis was detected by Annexin V-EGFP/PI apoptosis detection kit. Cell autophagy was checked using GFP-RFP-LC3 ratiometric plasmid. The roles of VPA in lung aging were investigated by in vivo experiments using H&E and Masson staining, WB, as well as electronic microscope strategies. RESULTS: Here we identified VPA was able to induce an over-accumulation of reactive oxygen species (ROS) (>1.5 times increasing) and apoptosis (>2 times increasing) of senescent cells. Mechanistically, VPA activated the phospholipid modifying enzyme membrane-bound O-acyltransferase domain-containing protein 1 (MBOAT1), which was repressed during senescence, then promoted mitochondrial autophagy and apoptosis. In addition, VPA was also found to alleviate therapy induced abnormal mitochondria and lung aging phenotype (>1.5 times decreasing of lung fibrosis markers and >2.5 times increasing of naïve/memory CD4+ or CD8+ T cells) in vivo. CONCLUSION: Taken together, our study demonstrated that VPA was able to selectively kill senescent cells both in vitro and in vivo, and thus shedding light on new functions and novel potential application of VPA in anti-aging and anti-age-associated diseases.

In-situ synthesized perovskite/polyhedral oligomeric silsesquioxane nanocomposites for robust X-ray imaging.

Perovskites are extensively studied in scintillation detection due to their low cost, simple synthesis, high scintillation light yield, and rapid decay times. However, their instability to light and radiation leads to scintillation performance degradation. To address these stability concerns, this paper proposes a new perovskite nanocrystal (NC) synthesis method that employs aminopropyllsobutyl polyhedral oligomeric silsesquioxane (POSS) as a ligand and a coating layer to passivate the perovskite NCs, significantly enhancing their stability and photoluminescence efficiency. Furthermore, the resultant perovskite/aminopropyllsobutyl POSS nanocomposites exhibit remarkable capabilities in X-ray detection limits, imaging quality, and radiation hardness. These findings underscore the potential of enhanced perovskite in revolutionizing the field of scintillator materials, offering promising pathways for their future applications and development.

The foundation of the rhubarb industry economy: investigating metabolites disparities of rhubarb between varieties and growing environments on the Tibetan plate.

Objective: In Tibetan dietary and folk medicine practices, Rheum austral is commonly used as an alternative to Rheum tanguticum, and there is a prevailing belief that wild rhubarb should not be substituted by its cultivated counterpart. However, these traditions are not supported by scientific evidence, particularly concerning the differences in endogenous metabolites between cultivated and wild rhubarbs, as well as between officially recognized and non-official rhubarbs. These uncertainties have also been hindering the vertical integration development of the local rhubarb industry. Methods: In this study, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOFMS) and biostatistical analysis were employed to systematically and comprehensively investigate the chemical constituents of rhubarbs from various sources, focusing on the differences in metabolic components between cultivated and wild rhubarbs. Results: The metabolic differences in rhubarb from various varieties and environments are pronounced. Among them, 39 differential metabolites were identified between cultivated R. tanguticum and wild R. tanguticum. cultivated R. tanguticum is rich in emodin, physcion, and rhapontigenin, whereas wild R. tanguticum exhibits a higher concentration of rhaponticin and is particularly abundant in anthraquinone compounds. Additionally, 33 differential metabolites distinguished wild R. tanguticum from wild R. austral, with R. austral being rich in stilbene derivatives and wild R. tanguticum predominantly containing coumarins. The correlations among these differential metabolites have also been further explored and presented. Conclusion: The metabolic disparities between cultivated and wild rhubarb varieties are substantial, with wild rhuabarb containing higher levels of effective components than its cultivated counterparts. However, wild varieties face issues with component instability and resource depletion, while cultivated varieties exhibit more stable effective components. Given these significant differences in metabolic components, it is essential to differentiate rhubarbs from various species and growing conditions to suit specific medicinal and dietary purposes effectively. This paper can lay a theoretical foundation for the vertical integration development of the rhubarb industry in Tibetan areas.

Urgency as a predictor of change in emotion dysregulation in adolescents.

Introduction: Adolescence is a key developmental period characterized by increased maladaptive risky behaviors. Two related but distinct constructs, urgency (the tendency to act rashly in response to strong negative or positive emotions) and emotion dysregulation, are important risk factors for engaging in maladaptive risky behaviors. Thus far, research has largely agreed that these two risk factors are highly correlated. However, the causal direction between these constructs is less understood. The goal of the current study is to determine whether urgency predicts emotion dysregulation change among adolescents. Method: This project is an analysis of 544 youth (49.8% female, Mage=14.22, SD=0.52). We tested whether urgency at baseline predicts change in emotion dysregulation over a nine-week period, and whether that relationship differs across boys and girls. Results: Two multigroup latent change score path analyses found that negative, but not positive, urgency significantly predicted emotion dysregulation change (negative urgency: b= -0.57, p=0.001; positive urgency: b=0.22, p=0.06). There was no evidence of moderation by gender. Discussion: This work provides initial evidence of a temporal relationship between higher negative urgency and increased emotion dysregulation. The next step is to determine whether negative urgency imparts risk for maladaptive behaviors through its effect on emotion dysregulation. The long-term goal of this program of research is to design and test interventions to reduce the impact of negative urgency for adolescent risk-taking.

Reversible Co(II)-Co(III) Transformation in a Family of Metal-Dipyrazolate Frameworks.

Transformation between oxidation states is widespread in transition metal coordination chemistry and biochemistry, typically occurring in solution. However, air-induced oxidation in porous crystalline solids with retention of crystallinity is rare due to the dearth of materials with high structural stability that are inherently redox active. Herein, we report a new family of such materials, four isostructural cobalt-pyrazolate frameworks of face-centered cubic, fcu, topology, fcu-L-Co, that are sustained by Co8 molecular building blocks (MBBs) and dipyrazolate ligands, L. fcu-L-Co were observed to spontaneously transform from Co(II)8 to Co(III)8 MBBs in air with retention of crystallinity, marking the first such instance in metal-organic frameworks (MOFs). This transformation can also be achieved through water vapor sorption cycling, heating, or chemical oxidation. The reverse reactions were conducted by exposure of fcu-L-Co(III) to aqueous hydrazine. fcu-L-Co(II) exhibited high gravimetric water vapor uptakes of 0.55-0.68 g g-1 at 30% relative humidity (RH), while in fcu-L-Co(III) the inflection point shifted to lower RH and framework stability improved. Insight into the transformation between fcu-L-Co(II) and fcu-L-Co(III) was gained from single crystal X-ray diffraction and in situ spectroscopy. Overall, the crystal engineering approach we adopted has afforded a new family of MOFs that exhibit cobalt redox chemistry in a confined space coupled with high porosity.

Numerical model for solid-like and fluid-like behavior of granular flows.

We propose a constitutive model for both the solid-like and fluid-like behavior of granular materials by decomposing the stress tensor into quasi-static and collisional components. A hypoplastic model is adopted for the solid-like behavior in the quasi-static regime, while the viscous and dilatant behavior in the fluid-like regime is represented by a modified µ ( I ) rheology model. This model effectively captures the transition between solid-like and fluid-like flows. Performance and validation of the proposed model are demonstrated through numerical simulations of element tests.

Privacy Preserving Technology using Federated Learning and Blockchain in protecting against Adversarial Attacks for Retinal Imaging.

PURPOSE: Collaboration provides valuable data for robust artificial intelligence (AI) model development. Federated learning (FL) is a privacy enhancing technology that allows collaboration while respecting privacy via the development of models without raw data transfer. However state-of-the-art FL models still face challenges in non-independent and identically distributed (non-i.i.d.) health care settings and remain susceptible to privacy breaches. We propose a novel FL framework coupled with blockchain technology to address these challenges. DESIGN: Retrospective multicohort study SUBJECTS AND METHODS: 27,145 images from Singapore, China and Taiwan were used to design a novel FL aggregation method for the detection of myopic macular degeneration (MMD) from fundus photographs and macular disease from optical coherence tomography (OCT) scans in feature distribution skew and label distribution imbalance scenarios. We further performed adversarial attacks (label flipping and clean label). As proof of concept, blockchain was incorporated into FL to demonstrate secure transfer of model updates across collaborating sites. MAIN OUTCOME MEASURES: We evaluated our FL model performance in MMD and OCT classification and compared our model against state-of the-art FL and centralized models. RESULTS: Our FL model showed robust performance with areas under the receiving operating characteristic curves (AUC) of 0.868±0.009 for MMD detection and 0.970±0.012 for OCT macular disease classification. In label flipping attack, our FL model had an AUC of 0.861±0.019, similar to the centralized model (AUC 0.856± 0.015) and higher than other FL models (AUC 0.578-0.819) In clean label attack, our FL model had an AUC of 0.878±0.006 which was comparable to the centralized model (AUC 0.878±0.001) and superior to other state-of-the-art FL models with AUC of 0.529-0.838. Simulation showed that the additional time with blockchain in one global epoch was around 5 seconds. The addition of blockchain to the FL framework was feasible with a minimal impact on model development time. CONCLUSIONS: Our proposed FL algorithm overcomes the shortcoming of the traditional FL in non i.i.d. situations and remains robust to against adversarial attacks. The integration of blockchain adds further security during the transfer of model updates. Blockchain-enabled FL can be a trusted platform for collaborative health AI research.