Phase 1 study of safety and preliminary efficacy of intranasal transplantation of human neural stem cells (ANGE-S003) in Parkinson's disease.

BACKGROUND: Intranasal transplantation of ANGE-S003 human neural stem cells showed therapeutic effects and were safe in preclinical models of Parkinson's disease (PD). We investigated the safety and tolerability of this treatment in patients with PD and whether these effects would be apparent in a clinical trial. METHODS: This was a 12-month, single-centre, open-label, dose-escalation phase 1 study of 18 patients with advanced PD assigned to four-time intranasal transplantation of 1 of 3 doses: 1.5 million, 5 million or 15 million of ANGE-S003 human neural stem cells to evaluate their safety and efficacy. RESULTS: 7 patients experienced a total of 14 adverse events in the 12 months of follow-up after treatment. There were no serious adverse events related to ANGE-S003. Safety testing disclosed no safety concerns. Brain MRI revealed no mass formation. In 16 patients who had 12-month Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) data, significant improvement of MDS-UPDRS total score was observed at all time points (p<0.001), starting with month 3 and sustained till month 12. The most substantial improvement was seen at month 6 with a mean reduction of 19.9 points (95% CI, 9.6 to 30.3; p<0.001). There was no association between improvement in clinical outcome measures and cell dose levels. CONCLUSIONS: Treatment with ANGE-S003 is feasible, generally safe and well tolerated, associated with functional improvement in clinical outcomes with peak efficacy achieved at month 6. Intranasal transplantation of neural stem cells represents a new avenue for the treatment of PD, and a larger, longer-term, randomised, controlled phase 2 trial is warranted for further investigation.

Imageable Brachytherapy with Chelator-Free Radiolabeling Hydrogel.

Brachytherapy stands as an essential clinical approach for combating locally advanced tumors. Here, an injectable brachytherapy hydrogel is developed for the treatment of both local and metastatic tumor. Fe-tannins nanoparticles are efficiently and stably radiolabeled with clinical used therapeutic radionuclides (such as 131I, 90Y, 177Lu and 225Ac) without a chelator, and then chemically cross-linked with 4-ArmPEG-SH to form brachytherapy hydrogel. Upon intratumoral administration, magnetic resonance imaging (MRI) signal from ferric ions embedded within the hydrogel directly correlates with the retention dosage of radionuclides, which can real-time monitor radionuclides emitting short-range rays in vivo without penetration limitation during brachytherapy. The hydrogel's design ensures the long-term tumor retention of therapeutic radionuclides, leading to the effective eradication of local tumor. Furthermore, the radiolabeled hydrogel is integrated with an adjuvant to synergize with immune checkpoint blocking therapy, thereby activating potent anti-tumor immune responses and inhibiting metastatic tumor growth. Therefore, this work presents an imageable brachytherapy hydrogel for real-time monitoring therapeutic process, and expands the indications of brachytherapy from treatment of localized tumors to metastatic tumors. This article is protected by copyright. All rights reserved.

Yiqigubiao pill treatment regulates Sirtuin 5 expression and mitochondrial function in chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of pathophysiological bases of airway inflammation and its anti-inflammatory response. Aberrant mitochondrial signaling and mitochondrial dysfunction underlie the pathomechanisms leading to COPD. This study aims to investigate the effects of the Yiqigubiao (YQGB) pill, a traditional Chinese medicine (TCM), on Sirtuin 5 (SIRT5) and mitochondrial function in patients with COPD. Methods: Thirty-four patients with COPD were randomized into oral YQGB or placebo groups concurrent with a 24-week routine treatment. The pulmonary function was assessed by examining the levels of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC), FEV1, and FVC. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect SIRT5 expression in mitochondria isolated from peripheral blood. Flow cytometry was used to detect changes in mitochondrial membrane potential and reactive oxygen species (ROS) in peripheral blood lymphocytes. Human bronchial epithelial (HBE) cells stimulated by cigarette smoke extract (CSE) were treated with YQGB. After SIRT5 was knocked down in cells, the changes in mitochondrial membrane potential, levels of adenosine triphosphate (ATP), and ROS were detected. Results: YQGB treatment significantly improved lung function in patients with COPD. The expression of SIRT5 and the mitochondrial membrane potential significantly increased and ROS decreased in patients with COPD after YQGB treatment. The CSE decreased cell proliferation and SIRT5 expression, which was alleviated after YQGB treatment. Furthermore, SIRT5 was knocked down in CSE-stimulated HBE cells, and its expression was elevated upon YQGB treatment. The knockdown of SIRT5 significantly altered the CSE-stimulation-induced dysregulation of mitochondrial membrane potential, ATP levels, and ROS. This was also restored after YQGB treatment. Conclusions: YQGB treatment can elevate SIRT5 expression, restore mitochondrial function in COPD, and exert protective effects.

Ventral subiculum promotes wakefulness through several pathways in male mice.

The ventral subiculum (vSUB), the major output structure of the hippocampal formation, regulates motivation, stress integration, and anxiety-like behaviors that rely on heightened arousal. However, the roles and underlying neural circuits of the vSUB in wakefulness are poorly known. Using in vivo fiber photometry and multichannel electrophysiological recordings in mice, we found that the vSUB glutamatergic neurons exhibited high activities during wakefulness. Moreover, activation of vSUB glutamatergic neurons caused an increase in wakefulness and anxiety-like behaviors and induced a rapid transition from sleep to wakefulness. In addition, optogenetic stimulation of vSUB glutamatergic terminals and retrograde-targeted chemogenetic activation of vSUB glutamatergic neurons revealed that vSUB promoted arousal by innervating the lateral hypothalamus (LH), nucleus accumbens (NAc) shell, and prefrontal cortex (PFC). Nevertheless, local microinjection of dopamine D1 or D2/D3 receptor antagonist blocked the wake-promoting effect induced by chemogenetic activation of vSUB pathways. Finally, chemogenetic inhibition of vSUB glutamatergic neurons decreased arousal. Altogether, our findings reveal a prominent contribution of vSUB glutamatergic neurons to the control of wakefulness through several pathways.

Analysis of tissue tropism of GCRV-II infection in grass carp using a VP35 monoclonal antibody.

Grass carp, one of the major freshwater aquaculture species in China, is susceptible to grass carp reovirus (GCRV). GCRV is a non-enveloped RNA virus and has a double-layered capsid, causing hemorrhagic disease and high mortalities in infected fish. However, the tropism of GCRV infection has not been investigated. In this study, monoclonal antibodies against recombinant VP35 protein were generated in mice and characterized. The antibodies exhibited specific binding to the N terminal region (1-155 aa) of the recombinant VP35 protein expressed in the HEK293 cells, and native VP35 protein in the GCRV-II infected CIK cells. Immunofluorescent staining revealed that viruses aggregated in the cytoplasm of infected cells. In vivo challenge experiments showed that high levels of GCRV-II viruses were present in the gills, intestine, spleen and liver, indicating that they are the major sites for virus infection. Our study showed that the VP35 antibodies generated in this study exhibited high specificity, and are valuable for the development of diagnostic tools for GCRV-II infection.

High-efficiency self-focusing metamaterial grating coupler in silicon nitride with amorphous silicon overlay.

Efficient fiber-chip coupling interfaces are critically important for integrated photonics. Since surface gratings diffract optical signals vertically out of the chip, these couplers can be placed anywhere in the circuit allowing for wafer-scale testing. While state-of-the-art grating couplers have been developed for silicon-on-insulator (SOI) waveguides, the moderate index contrast of silicon nitride (SiN) presents an outstanding challenge for implementing efficient surface grating couplers on this platform. Due to the reduced grating strength, a longer structure is required to radiate the light from the chip which produces a diffracted field that is too wide to couple into the fiber. In this work, we present a novel grating coupler architecture for silicon nitride photonic integrated circuits that utilizes an amorphous silicon (α-Si) overlay. The high refractive index of the α-Si overlay breaks the coupler's vertical symmetry which increases the directionality. We implement subwavelength metamaterial apodization to optimize the overlap of the diffracted field with the optical fiber Gaussian mode profile. Furthermore, the phase of the diffracted beam is engineered to focalize the field into an SMF-28 optical fiber placed 55 µm above the surface of the chip. The coupler was designed using rigorous three-dimensional (3D) finite-difference time-domain (FDTD) simulations supported by genetic algorithm optimization. Our grating coupler has a footprint of 26.8 × 32.7 µm2 and operates in the O-band centered at 1.31 µm. It achieves a high directionality of 85% and a field overlap of 90% with a target fiber mode size of 9.2 µm at the focal plane. Our simulations predict a peak coupling efficiency of - 1.3 dB with a 1-dB bandwidth of 31 nm. The α-Si/SiN grating architecture presented in this work enables the development of compact and efficient optical interfaces for SiN integrated photonics circuits with applications including optical communications, sensing, and quantum photonics.

Epigenetic regulation of high light-induced anthocyanin biosynthesis by histone demethylase IBM1 in Arabidopsis.

In plant species, anthocyanin accumulation is specifically regulated by light signaling. Although the CONSTITUTIVELY PHOTOMORPHOGENIC1/SUPPRESSOR OF PHYA-105 (COP1/SPA) complex is known to control anthocyanin biosynthesis in response to light, the precise mechanism underlying this process remains largely unknown. Here, we report that Increase in BONSAI Methylation 1 (IBM1), a JmjC domain-containing histone demethylase, participates in the regulation of light-induced anthocyanin biosynthesis in Arabidopsis. The expression of IBM1 was induced by high light (HL) stress, and loss-of-function mutations in IBM1 led to accelerated anthocyanin accumulation under HL conditions. We further identified that IBM1 is directly associated with SPA1/3/4 chromatin in vivo to establish a hypomethylation status on H3K9 and DNA non-CG at these loci under HL, thereby releasing their expression. Genetic analysis showed that quadruple mutants of IBM1 and SPA1/3/4 resemble spa134 mutants. Overexpression of SPA1 in ibm1 mutants complements the mutant phenotype. Our results elucidate the significance and mechanism of IBM1 histone demethylase in the epigenetic regulation of anthocyanin biosynthesis in Arabidopsis under HL conditions.

Decreasing circ_0014614 promotes the differentiation of bone marrow flineage cells into megakaryocytes in essential thrombocythemia via activiation of miR-138-5p/caspase3 axis.

BACKGROUND: Circular RNAs (circRNA) are pivotal in hematological diseases. Previous study showed that circ_0014614 (circDAP3) was significantly underexpressed in bone marrow-derived exosomes from essential thrombocythemia (ET) patients, affecting the differentiation of bone marrow lineage cells into megakaryocytes. METHODS: Fluorescence in situ hybridization (FISH) was used to display circ_0014614's primary cytoplasmic location in K562 cells. Cytoscape software was used to predict the circRNA-miRNA-mRNA networks, and their expression at the cellular level was detected by Quantitative reverse transcription-polymerase chain reaction (qRT-PCR). qRT-PCR was utilized to detect the expression levels of circ_0014614，miR-138-5p and caspase3 mRNA. Western blot was used to determine the protein levels of GATA-1, RUNX-1, NF-E2, CD41 and caspase3. The proliferation of K562 cells was assessed using the Cell Counting Kit-8 (CCK-8) Assay. Furthermore, the interplay between miR-138-5p and circ_0014614 or caspase3 was elucidated through a Dual-luciferase reporter assay. RESULTS: FISH assay indicated circ_0014614's primary cytoplasmic location in K562 cells. In ET bone marrow and K562 cells, circ_0014614 and caspase3 were down-regulated, whereas miR-138-5p saw a significant surge. Overexpressing circ_0014614 curtailed K562 cells' proliferation and differentiation. Further, circ_0014614 targeted miR-138-5p, with heightened miR-138-5p levels counteracting circ_0014614's inhibition. MiR-138-5p further targeted caspase3, and caspase3 silencing neutralized suppressed miR-138-5p's effects on K562 cell differentiation. CONCLUSION: Circ_0014614 was down-regulated in ET bone marrow and bone marrow lineage cells, and upregulating circ_0014614 can inhibit bone marrow lineage cells' proliferation and differentiation into megakaryocytes. Mechanistically, circ_0014614 functioned as ceRNA via sponging miR-138-5p and alleviated the inhibitory effect of miR-138-5p on its target caspase3, which potentially deters tumor activity in ET.

InvPT++: Inverted Pyramid Multi-Task Transformer for Visual Scene Understanding.

Multi-task scene understanding aims to design models that can simultaneously predict several scene understanding tasks with one versatile model. Previous studies typically process multi-task features in a more local way, and thus cannot effectively learn spatially global and cross-task interactions, which hampers the models' ability to fully leverage the consistency of various tasks in multi-task learning. To tackle this problem, we propose an Inverted Pyramid multi-task Transformer, capable of modeling cross-task interaction among spatial features of different tasks in a global context. Specifically, we first utilize a transformer encoder to capture task-generic features for all tasks. And then, we design a transformer decoder to establish spatial and cross-task interaction globally, and a novel UP-Transformer block is devised to increase the resolutions of multi-task features gradually and establish cross-task interaction at different scales. Furthermore, two types of Cross-Scale Self-Attention modules, i.e., Fusion Attention and Selective Attention, are proposed to efficiently facilitate cross-task interaction across different feature scales. An Encoder Feature Aggregation strategy is further introduced to better model multi-scale information in the decoder. Comprehensive experiments on several 2D/3D multi-task benchmarks clearly demonstrate our proposal's effectiveness, establishing significant state-of-the-art performances. The codes are publicly available https://github.com/prismformore/Multi-Task-Transformer/tree/main/InvPT.

Comparison of systematic and combined biopsy for the detection of prostate cancer.

ABSTRACT: Systematic prostate biopsy has limitations, such as overdiagnosis of clinically insignificant prostate cancer and underdiagnosis of clinically significant prostate cancer. Magnetic resonance imaging (MRI)-guided biopsy, a promising alternative, might improve diagnostic accuracy. To compare the cancer detection rates of systematic biopsy and combined biopsy (systematic biopsy plus MRI-targeted biopsy) in Asian men, we conducted a retrospective cohort study of men who underwent either systematic biopsy or combined biopsy at two medical centers (Queen Mary Hospital and Tung Wah Hospital, Hong Kong, China) from July 2015 to December 2022. Descriptive statistics were calculated, and univariate and multivariate logistic regression analyses were performed. The primary and secondary outcomes were prostate cancer and clinically significant prostate cancer. A total of 1391 participants were enrolled. The overall prostate cancer detection rates did not significantly differ between the two groups (36.3% vs 36.6%, odds ratio [OR] = 1.01, 95% confidence interval [CI]: 0.81-1.26, P = 0.92). However, combined biopsy showed a significant advantage in detecting clinically significant prostate cancer (Gleason score ≥ 3+4) in patients with a total serum prostate-specific antigen (tPSA) concentration of 2-10 ng ml-1 (systematic vs combined: 11.9% vs 17.5%, OR = 1.58, 95% CI: 1.08-2.31, P = 0.02). Specifically, in the transperineal biopsy subgroup, combined biopsy significantly outperformed systematic biopsy in the detection of clinically significant prostate cancer (systematic vs combined: 12.6% vs 24.0%, OR = 2.19, 95% CI: 1.21-3.97, P = 0.01). These findings suggest that in patients with a tPSA concentration of 2-10 ng ml-1, MRI-targeted biopsy may be of greater predictive value than systematic biopsy in the detection of clinically significant prostate cancer.

Whole-genome resequencing of Hu sheep identifies candidate genes associated with agronomic traits.

The phenotypic diversity resulting from artificial or natural selection of sheep has made a significant contribution to human civilization. Hu sheep are a local sheep breed unique to China with high reproductive rates and rapid growth. Genome selection signatures have been widely used to investigate the genetic mechanisms underlying phenotypic variation in livestock. Here, we conduct whole-genome sequencing of 207 Hu sheep and compare them with the wild ancestors of domestic sheep (Asiatic mouflon) to investigate the genetic characteristics and selection signatures of Hu sheep. Based on six signatures of selection approaches, we detect genomic regions containing genes related to reproduction (BMPR1B, BMP2, PGFS, CYP19, CAMK4, GGT5, and GNAQ), vision (ALDH1A2, SAG, and PDE6B), nervous system (NAV1), and immune response (GPR35, SH2B2, PIK3R3, and HRAS). Association analysis with a population of 1299 Hu sheep reveal those missense mutations in the GPR35 (GPR35 g.952651 A>G; GPR35 g.952496 C>T) and NAV1 (NAV1 g.84216190 C>T; NAV1 g.84227412 G>A) genes are significantly associated (P < 0.05) with immune and growth traits in Hu sheep, respectively. This research offers unique insights into the selection characteristics of Hu sheep and facilitates further genetic improvement and molecular investigations.

Quantifying H&E staining results, grading and predicting IDH mutation status of gliomas using hybrid multi-dimensional MRI.

OBJECTIVE: To assess the performance of hybrid multi-dimensional magnetic resonance imaging (HM-MRI) in quantifying hematoxylin and eosin (H&E) staining results, grading and predicting isocitrate dehydrogenase (IDH) mutation status of gliomas. MATERIALS AND METHODS: Included were 71 glioma patients (mean age, 50.17 ± 13.38 years; 35 men). HM-MRI images were collected at five different echo times (80-200 ms) with seven b-values (0-3000 s/mm2). A modified three-compartment model with very-slow, slow and fast diffusion components was applied to calculate HM-MRI metrics, including fractions, diffusion coefficients and T2 values of each component. Pearson correlation analysis was performed between HM-MRI derived fractions and H&E staining derived percentages. HM-MRI metrics were compared between high-grade and low-grade gliomas, and between IDH-wild and IDH-mutant gliomas. Using receiver operational characteristic (ROC) analysis, the diagnostic performance of HM-MRI in grading and genotyping was compared with mono-exponential models. RESULTS: HM-MRI metrics FDvery-slow and FDslow demonstrated a significant correlation with the H&E staining results (p < .05). Besides, FDvery-slow showed the highest area under ROC curve (AUC = 0.854) for grading, while Dslow showed the highest AUC (0.845) for genotyping. Furthermore, a combination of HM-MRI metrics FDvery-slow and T2Dslow improved the diagnostic performance for grading (AUC = 0.876). DISCUSSION: HM-MRI can aid in non-invasive diagnosis of gliomas.

Turning pain into strength: prosocial behaviours in coping with trauma.

Background: Various coping strategies have been shown to alleviate the negative effects of trauma, yet the significance of prosocial behaviour in this realm has been notably underexplored. The present study explored the hypothesis that engaging in prosocial behaviour mitigates the impacts of trauma by promoting a sense of competence and relatedness, post-traumatic growth (PTG), and reconstruction of meaning.Methods: Three consecutive studies were conducted with college students to compare differences in consequence of prosocial behaviours between a trauma group and a control group. Study 1 (N = 96) used self-reported experiences of traumatic vs non-traumatic events; Study 2 (N = 43) used exposure vs. no exposure to video of an earthquake; Study 3 (N = 20) used a randomized controlled trial (RCT) of a prosocial-themed intervention vs. no intervention. Outcomes in all studies were assessed by self-report questionnaires.Results: Trauma damaged participants' sense of competence and meaningfulness. Prosocial behaviour relieved the impact of trauma on meaning, specifically manifested in the individuals' sense of meaningfulness and their search for meaning. Group interventions with a prosocial theme (based on effect size results) reduced post-traumatic stress disorder (PTSD) and enhanced PTG in victims. The promoting effect on PTG persisted a month later, and its enhancing effect on meaning manifested with a delay.Conclusion: Prosocial behaviour can potentially serve as a beneficial strategy for individuals coping with trauma because it helps enhance meaning and promotes PTG in victims. This conclusion is supported by laboratory experiments and a tentative small-scale intervention study, which provide an innovative perspective for future trauma interventions.

Prosocial behaviour can potentially serve as a beneficial strategy for individuals coping with trauma.Prosocial behaviour relieved the impact of trauma on meaning.Prosocial-themed intervention reduced PTSD and enhanced PTG in victims (based on effect size results).

Theoretical Study on Ion Diffusion Mechanism in W-Doped K3SbS4 as Solid-State Electrolyte for K-Ion Batteries.

The development of a solid-state electrolyte (SSE) is crucial for overcoming the side reactions of metal potassium anodes and advancing the progress of K-ion batteries (KIBs). Exploring the diffusion mechanism of the K ion in SSE is important for deepening our understanding and promoting its development. In this study, we conducted static calculations and utilized deep potential molecular dynamics (DeepMD) to investigate the behavior of cubic K3SbS4. The original K3SbS4 exhibited poor ionic conductivity, but we discovered that introducing heterovalent tungsten doping created vacancies, which significantly reduced the activation energy to 0.12 eV and enhanced the ionic conductivity to 1.80 × 10-2 S/cm. The diffusion of K-ions in K3SbS4 primarily occurs through the exchange of positions with K vacancies. This research provides insights into the design of SSE with high ionic conductivity. Furthermore, it highlights the effectiveness of DeepMD as a powerful tool for studying the SSE.

The integration of single-cell and bulk RNA-seq atlas reveals ERS-mediated acinar cell damage in acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a clinically common acute abdominal disease, whose pathogenesis remains unclear. The severe patients usually have multiple complications and lack specific drugs, leading to a high mortality and poor outcome. Acinar cells are recognized as the initial site of AP. However, there are no precise single-cell transcriptomic profiles to decipher the landscape of acinar cells during AP, which are the missing pieces of jigsaw we aimed to complete in this study. METHODS: A single-cell sequencing dataset was used to identify the cell types in pancreas of AP mice and to depict the transcriptomic maps in acinar cells. The pathways' activities were evaluated by gene sets enrichment analysis (GSEA) and single-cell gene sets variation analysis (GSVA). Pseudotime analysis was performed to describe the development trajectories of acinar cells. We also constructed the protein-protein interaction (PPI) network and identified the hub genes. Another independent single-cell sequencing dataset of pancreas samples from AP mice and a bulk RNA sequencing dataset of peripheral blood samples from AP patients were also analyzed. RESULTS: In this study, we identified genetic markers of each cell type in the pancreas of AP mice based on single-cell sequencing datasets and analyzed the transcription changes in acinar cells. We found that acinar cells featured acinar-ductal metaplasia (ADM), as well as increased endocytosis and vesicle transport activity during AP. Notably, the endoplasmic reticulum stress (ERS) and ER-associated degradation (ERAD) pathways activated by accumulation of unfolded/misfolded proteins in acinar cells could be pivotal for the development of AP. CONCLUSION: We deciphered the distinct roadmap of acinar cells in the early stage of AP at single-cell level. ERS and ERAD pathways are crucially important for acinar homeostasis and the pathogenesis of AP.

The feasibility of half-dose contrast-enhanced scanning of brain tumours at 5.0 T: a preliminary study.

PURPOSE: This study investigated and compared the effects of Gd enhancement on brain tumours with a half-dose of contrast medium at 5.0 T and with a full dose at 3.0 T. METHODS: Twelve subjects diagnosed with brain tumours were included in this study and underwent MRI after contrast agent injection at 3.0 T (full dose) or 5.0 T (half dose) with a 3D T1-weighted gradient echo sequence. The postcontrast images were compared by two independent neuroradiologists in terms of the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and subjective image quality score on a ten-point Likert scale. Quantitative indices and subjective quality ratings were compared with paired Student's t tests, and interreader agreement was assessed with the intraclass correlation coefficient (ICC). RESULTS: A total of 16 enhanced tumour lesions were detected. The SNR was significantly greater at 5.0 T than at 3.0 T in grey matter, white matter and enhanced lesions (p < 0.001). The CNR was also significantly greater at 5.0 T than at 3.0 T for grey matter/tumour lesions, white matter/tumour lesions, and grey matter/white matter (p < 0.001). Subjective evaluation revealed that the internal structure and outline of the tumour lesions were more clearly displayed with a half-dose at 5.0 T (Likert scale 8.1 ± 0.3 at 3.0 T, 8.9 ± 0.3 at 5.0 T, p < 0.001), and the effects of enhancement in the lesions were comparable to those with a full dose at 3.0 T (7.8 ± 0.3 at 3.0 T, 8.7 ± 0.4 at 5.0 T, p < 0.001). All subjective scores were good to excellent at both 5.0 T and 3.0 T. CONCLUSION: Both quantitative and subjective evaluation parameters suggested that half-dose enhanced scanning via 5.0 T MRI might be feasible for meeting clinical diagnostic requirements, as the image quality remains optimal. Enhanced scanning at 5.0 T with a half-dose of contrast agents might benefit patients with conditions that require less intravenous contrast agent, such as renal dysfunction.

ChatGPT4's Proficiency in Addressing Patients' Questions on Systemic Lupus Erythematosus: A Blinded Comparative Study with Specialists.

OBJECTIVES: The efficacy of artificial intelligence (AI)-driven chatbots like ChatGPT4 in specialized medical consultations, particularly in rheumatology, remains underexplored. This study compares the proficiency of ChatGPT4' responses with practicing rheumatologists to inquiries from patients with systemic lupus erythematosus (SLE). METHODS: In this cross-sectional study, we curated 95 frequently asked questions (FAQs), including 55 in Chinese and 40 in English. Responses for FAQs from ChatGPT4 and 5 rheumatologists were scored separately by a panel of rheumatologists and a group of patients with SLE across 6 domains (scientific validity, logical consistency, comprehensibility, completeness, satisfaction level, and empathy) on a 0-10 scale (a score of 0 indicates entirely incorrect responses, while 10 indicates accurate and comprehensive answers). RESULTS: Rheumatologists' scoring revealed that ChatGPT4-generated responses outperformed those from rheumatologists in satisfaction level and empathy, with mean differences of 0.537 (95% CI, 0.252-0.823; p < 0.01) and 0.460 (95% CI, 0.227-0.693 p < 0.01), respectively. From the SLE patients' perspective, ChatGPT4-generated responses were comparable to the rheumatologist-provided answers in all 6 domains. Subgroup analysis revealed ChatGPT4 responses were more logically consistent and complete regardless of language, and exhibited greater comprehensibility, satisfaction, and empathy in Chinese. However, ChatGPT4 responses were inferior in comprehensibility for English FAQs. CONCLUSION: ChatGPT4 demonstrated comparable, possibly better in certain domains, to address FAQs from patients with SLE, when compared with the answers provided by specialists. This study showed the potential of applying ChatGPT4 to improve consultation in SLE patients.

Preparation and characterization of quercetin@ZIF-L/GO@AgNPs nanocomposite film for room-temperature strawberry preservation.

Fresh strawberries are easily contaminated by microorganisms after picking. Therefore, how to effectively store and keep fresh strawberries has been a hot topic for scientists to study. In this study, we prepared a leaf shaped metal organic framework nanomaterial loaded with quercetin (Quercetin@ZIF-L) at first, which can achieve effective loading of quercetin (96%) within 45 min and has a controlled release effect under acidic conditions. In addition, by cleverly combining satellite graphene oxide @ silver nanoparticles (GO@AgNPs) with slow precipitation performance, Quercetin@ZIF-L/GO@AgNPs nanocomposite film with larger pore size and larger specific surface area was prepared by scraping method. The characterization data of water flux, retention rate, flux recovery rate and water vapor permeability show that the composite film has good physical properties. The experiment of film packaging showed that the fresh life of strawberry could be extended from 3 to 8 days, which significantly improved the storage and freshness cycle of strawberry. At the same time, the metal migration test proved that the residual amount of silver ion in strawberry met the EU standard and zinc ions are beneficial to the health, enriching the types of high-performance fresh-keeping materials and broadening the application.

Improvement on wheat bread quality by in situ produced dextran-A comprehensive review from the viewpoint of starch and gluten.

Deterioration of bread quality, characterized by the staling of bread crumb, the softening of bread crust and the loss of aroma, has caused a huge food waste and economic loss, which is a bottleneck restriction to the development of the breadmaking industry. Various bread improvers have been widely used to alleviate the issue. However, it is noteworthy that the sourdough technology has emerged as a pivotal factor in this regard. In sourdough, the metabolic breakdown of carbohydrates, proteins, and lipids leads to the production of exopolysaccharides, organic acids, aroma compounds, or prebiotics, which contributes to the preeminent ability of sourdough to enhance bread attributes. Moreover, sourdough exhibits a "green-label" feature, which satisfies the consumers' increasing demand for additive-free food products. In the past two decades, there has been a significant focus on sourdough with in situ produced dextran due to its exceptional performance. In this review, the behaviors of bread crucial compositions (i.e., starch and gluten) during dough mixing, proofing, baking and bread storing, as well as alterations induced by the acidic environment and the presence of dextran are systemically summarized. From the viewpoint of starch and gluten, results obtained confirm the synergistic amelioration on bread quality by the coadministration of acidity and dextran, and also highlight the central role of acidification. This review contributes to establishing a theoretical foundation for more effectively enhancing the quality of wheat breads through the application of in situ produced dextran.

Co-culture of benzalkonium chloride promotes the biofilm formation and decreases the antibiotic susceptibility of a Pseudomonas aeruginosa strain.

Benzalkonium chloride (BAC) is a disinfectant with broad-spectrum antibacterial properties, yet despite its widespread use and detection in the environment, the effects of BAC exposure on microorganisms remain poorly documented. Herein, the impacts of BAC on a Pseudomonas aeruginosa strain Jade-X were systematically investigated. The results demonstrated that the minimum inhibitory concentration (MIC) of BAC against strain Jade-X was 64 mg L-1. Exposure to BAC concentrations of 8, 16, 32, and 64 mg L-1 significantly augmented biofilm formation by 2.03-, 2.43-, 2.96-, and 2.56-fold respectively. The swimming and twitching abilities, along with the virulence factor production, were inhibited. Consistently, quantitative reverse transcription PCR assays revealed significant downregulation of genes related to flagellate- and pili-mediated motilities (flgD, flgE, pilB, pilQ, and motB), as well as phzA and phzB genes involved in pyocyanin production. The results of disk diffusion and MIC assays demonstrated that BAC decreased the antibiotic susceptibility of ciprofloxacin, levofloxacin, norfloxacin, and tetracycline. Conversely, an opposite trend was observed for polymyxin B and ceftriaxone. Genomic analysis revealed that strain Jade-X harbored eleven resistance-nodulation-cell division efflux pumps, with mexCD-oprJ exhibiting significant upregulation while mexEF-oprN and mexGHI-opmD were downregulated. In addition, the quorum sensing-related regulators LasR and RhlR were also suppressed, implying that BAC might modulate the physiological and biochemical behaviors of strain Jade-X by attenuating the quorum sensing system. This study enhances our understanding of interactions between BAC and P. aeruginosa, providing valuable insights to guide the regulation and rational use of BAC.