Histone chaperone HIRA, promyelocytic leukemia protein, and p62/SQSTM1 coordinate to regulate inflammation during cell senescence.

Cellular senescence, a stress-induced stable proliferation arrest associated with an inflammatory senescence-associated secretory phenotype (SASP), is a cause of aging. In senescent cells, cytoplasmic chromatin fragments (CCFs) activate SASP via the anti-viral cGAS/STING pathway. Promyelocytic leukemia (PML) protein organizes PML nuclear bodies (NBs), which are also involved in senescence and anti-viral immunity. The HIRA histone H3.3 chaperone localizes to PML NBs in senescent cells. Here, we show that HIRA and PML are essential for SASP expression, tightly linked to HIRA's localization to PML NBs. Inactivation of HIRA does not directly block expression of nuclear factor κB (NF-κB) target genes. Instead, an H3.3-independent HIRA function activates SASP through a CCF-cGAS-STING-TBK1-NF-κB pathway. HIRA physically interacts with p62/SQSTM1, an autophagy regulator and negative SASP regulator. HIRA and p62 co-localize in PML NBs, linked to their antagonistic regulation of SASP, with PML NBs controlling their spatial configuration. These results outline a role for HIRA and PML in the regulation of SASP.

The high-quality genome of Cryptotaenia japonica and comparative genomics analysis reveals anthocyanin biosynthesis in Apiaceae.

Cryptotaenia japonica, a traditional medicinal and edible vegetable crops, is well-known for its attractive flavors and health care functions. As a member of the Apiaceae family, the evolutionary trajectory and biological properties of C. japonica are not clearly understood. Here, we first reported a high-quality genome of C. japonica with a total length of 427 Mb and N50 length 50.76 Mb, was anchored into 10 chromosomes, which confirmed by chromosome (cytogenetic) analysis. Comparative genomic analysis revealed C. japonica exhibited low genetic redundancy, contained a higher percentage of single-cope gene families. The homoeologous blocks, Ks, and collinearity were analyzed among Apiaceae species contributed to the evidence that C. japonica lacked recent species-specific WGD. Through comparative genomic and transcriptomic analyses of Apiaceae species, we revealed the genetic basis of the production of anthocyanins. Several structural genes encoding enzymes and transcription factor genes of the anthocyanin biosynthesis pathway in different species were also identified. The CjANSa, CjDFRb, and CjF3H gene might be the target of Cjaponica_2.2062 (bHLH) and Cjaponica_1.3743 (MYB). Our findings provided a high-quality reference genome of C. japonica and offered new insights into Apiaceae evolution and biology.

Myeloid gasdermin D drives early-stage T cell immunity and peripheral inflammation in a mouse model of Alzheimer's disease.

BACKGROUND: It is now realized that peripheral inflammation and abnormal immune responses, especially T cells, contribute to the development of Alzheimer's disease (AD). Gasdermin D (GSDMD) -mediated pyroptosis has been associated with several neuroinflammatory diseases, but whether GSDMD is involved in the peripheral inflammation and T cell immunity during AD remains unclear. METHODS: We dynamically investigated GSDMD activation in the peripheral and central nervous system of 5×FAD mouse model and dissected the role of myeloid GSDMD using genetic knockout mice, especially its influence on peripheral T cell responses and AD inflammation. RNA sequencing and in vitro coculture were used to elucidate the underlying immune mechanisms involved. Targeted inhibitor experiments and clinical correlation analysis were used to further verify the function of GSDMD in AD. RESULTS: In the present study, caspase activated GSDMD in the spleen of 5×FAD mice earlier than in the brain during disease progression. Loss of myeloid cell GSDMD was shown to impair early-stage effector T cell activation in the periphery and prevent T cell infiltration into the brain, with an overall reduction in neuroinflammation. Furthermore, myeloid cell GSDMD induced T cell PD-1 expression through the IL-1ß/NF-κB pathway, restricting regulatory T cells. The administration of a GSDMD inhibitor combined with an anti-PD-1 antibody was found to mitigate the development of AD-associated inflammation. In some AD patients, plasma sPD-1 is positively correlated with IL-Iß and clinical features. CONCLUSIONS: Our study systematically identified a role for GSDMD in the AD-related peripheral inflammation and early-stage T cell immunity. These findings also suggest the therapeutic potential of targeting GSDMD for the early intervention in AD.

Deep Learning Model Based on Multisequence MRI Images for Assessing Adverse Pregnancy Outcome in Placenta Accreta.

BACKGROUND: Preoperative assessment of adverse outcomes risk in placenta accreta spectrum (PAS) disorders is of high clinical relevance for perioperative management and prognosis. PURPOSE: To investigate the association of preoperative MRI multisequence images and adverse pregnancy outcomes by establishing a deep learning model in patients with PAS. STUDY TYPE: Retrospective. POPULATION: 323 pregnant women (age from 20 to 46, the median age is 33), suspected of PAS, underwent MRI to assess the PAS, divided into the training (N = 227) and validation datasets (N = 96). FIELD STRENGTH/SEQUENCE: 1.5T scanner/fast imaging employing steady-state acquisition sequence and single shot fast spin echo sequence. ASSESSMENT: Different deep learning models (i.e., with single MRI input sequence/two sequences/multisequence) were compared to assess the risk of adverse pregnancy outcomes, which defined as intraoperative bleeding ≥1500 mL and/or hysterectomy. Net reclassification improvement (NRI) was used for quantitative comparison of assessing adverse pregnancy outcome between different models. STATISTICAL TESTS: The AUC, sensitivity, specificity, and accuracy were used for evaluation. The Shapiro-Wilk test and t-test were used. A P value of <0.05 was considered statistically significant. RESULTS: 215 cases were invasive placenta accreta (67.44% of them with adverse outcomes) and 108 cases were non-invasive placenta accreta (9.25% of them with adverse outcomes). The model with four sequences assessed adverse pregnancy outcomes with AUC of 0.8792 (95% CI, 0.8645-0.8939), with ACC of 85.93% (95%, 84.43%-87.43%), with SEN of 86.24% (95% CI, 82.46%-90.02%), and with SPC of 85.62% (95%, 82.00%-89.23%) on the test cohort. The performance of model with four sequences improved above 0.10 comparing with that of model with two sequences and above 0.20 comparing with that of model with single sequence in terms of NRI. DATA CONCLUSION: The proposed model showed good diagnostic performance for assessing adverse pregnancy outcomes. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Unlocking the potential of the 3-hydroxykynurenine/kynurenic acid ratio: a promising biomarker in adolescent major depressive disorder.

Metabolites disruptions in tryptophan (TRP) and kynurenine pathway (KP) are believed to disturb neurotransmitter homeostasis and contribute to depressive symptoms. This study aims to investigate serum levels of KP metabolites in adolescent major depressive disorder (AMDD), and examine their relationship with depression severities. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze serum levels of TRP, kynurenic acid (KYNA), kynurenine (KYN), and 3-hydroxy-kynurenine (3-HK) in 143 AMDD participants and 98 healthy controls (HC). Clinical data, including Children's Depression Inventory (CDI) scores, were collected and analyzed using statistical methods, such as ANOVA, logistic regression, Receiver operating characteristic curve analysis and a significance level of p < 0.05 was used for all analyses. AMDD showed significantly decreased serum levels of KYNA (-25.5%), KYN (-14.2%), TRP (-11.0%) and the KYNA/KYN ratio (-11.9%) compared to HC (p < 0.01). Conversely, significant increases were observed in 3-HK levels (+50.4%), the 3-HK/KYNA ratio (+104.3%) and the 3-HK/KYN ratio (+93.0%) (p < 0.01). Logistic regression analysis identified increased level of 3-HK as a contributing factor to AMDD, while increased level of KYNA acted as a protective factor against AMDD. The 3-HK/KYNA ratio demonstrated an area under the curve (AUC) of 0.952. This study didn't explore AMDD's inflammatory status and its metabolites relationship explicitly. These findings indicate that metabolites of TRP and KP may play a crucial role in the pathogenesis of AMDD, emphasizing the potential of the 3-HK/KYNA ratio as a laboratory biomarker for early detection and diagnosis of AMDD.

Broad/narrowband switchable terahertz absorber based on Dirac semimetal and strontium titanate for temperature sensing.

A broadband and narrowband switchable terahertz (THz) absorber based on a bulk Dirac semimetal (BDS) and strontium titanate (STO) is proposed. Narrowband and broadband absorption can be switched by adjusting the Fermi level of the BDS. When the Fermi level of the BDS is 100 meV, the device is an absorber with three narrowband absorption peaks. The frequencies are 0.44, 0.86, and 1.96 THz, respectively, when the temperature of STO is 250 K. By adjusting the temperature of STO from 250 to 500 K, the blue shifts of the frequencies are approximately 0.14, 0.32, and 0.60 THz, respectively. The sensitivities of the three absorption peaks are 0.56, 1.27, and 2.38 GHz/K, respectively. When the Fermi level of the BDS is adjusted from 100 to 30 meV, the device can be switched to a broadband absorber with a bandwidth of 0.70 THz. By adjusting the temperature of STO from 250 to 500 K, the central frequency shifts from 1.40 to 1.79 THz, and the bandwidth broadens from 0.70 to 0.96 THz. The sensitivity of the central frequency is 1.57 GHz/K. The absorber also has a wide range of potential applications in multifunctional tunable devices, such as temperature sensors, stealth equipment, and filters.

A prognostic four-gene signature and a therapeutic strategy for hepatocellular carcinoma: Construction and analysis of a circRNA-mediated competing endogenous RNA network.

BACKGROUND: Hepatocellular carcinoma (HCC) has a poor long-term prognosis. The competition of circular RNAs (circRNAs) with endogenous RNA is a novel tool for predicting HCC prognosis. Based on the alterations of circRNA regulatory networks, the analysis of gene modules related to HCC is feasible. METHODS: Multiple expression datasets and RNA element targeting prediction tools were used to construct a circRNA-microRNA-mRNA network in HCC. Gene function, pathway, and protein interaction analyses were performed for the differentially expressed genes (DEGs) in this regulatory network. In the protein-protein interaction network, hub genes were identified and subjected to regression analysis, producing an optimized four-gene signature for prognostic risk stratification in HCC patients. Anti-HCC drugs were excavated by assessing the DEGs between the low- and high-risk groups. A circRNA-microRNA-hub gene subnetwork was constructed, in which three hallmark genes, KIF4A, CCNA2, and PBK, were subjected to functional enrichment analysis. RESULTS: A four-gene signature (KIF4A, CCNA2, PBK, and ZWINT) that effectively estimated the overall survival and aided in prognostic risk assessment in the The Cancer Genome Atlas (TCGA) cohort and International Cancer Genome Consortium (ICGC) cohort was developed. CDK inhibitors, PI3K inhibitors, HDAC inhibitors, and EGFR inhibitors were predicted as four potential mechanisms of drug action (MOA) in high-risk HCC patients. Subsequent analysis has revealed that PBK, CCNA2, and KIF4A play a crucial role in regulating the tumor microenvironment by promoting immune cell invasion, regulating microsatellite instability (MSI), and exerting an impact on HCC progression. CONCLUSIONS: The present study highlights the role of the circRNA-related regulatory network, identifies a four-gene prognostic signature and biomarkers, and further identifies novel therapy for HCC.

Modified cardiopulmonary bypass circuit for transcatheter aortic valve implantation and emergent cardiac surgery.

Transcatheter aortic valve implantation (TAVI) has revolutionized the treatment of severe aortic stenosis in high-risk patients, offering a minimally invasive alternative to open-heart surgery. However, complications such as hemodynamic instability may require mechanical circulatory support. In some cases, emergent cardiac surgery may be required, necessitating a swift transition to cardiopulmonary bypass (CPB). We modified the CPB circuit allowing for circulatory support and easy transition to CPB. No bleeding or vascular complications were observed. The modified CPB circuit minimizes hemodynamic disruptions and allows for postoperative ECMO support.

Induction of apoptosis by oridonin in nonfunctioning pituitary adenoma cells.

Nonfunctioning pituitary adenoma (NFPA) is one of the major subtypes of pituitary adenomas (PA) and its primary treatment is surgical resection. However, normal surgery fails to remove lesions completely and there remains in lack of frontline treatment, so the development of new drugs for NFPA is no doubt urgent. Oridonin (ORI) has been reported to have antitumor effects on a variety of tumors, but whether it could exhibit the same effect on NFPA requires to be further investigated. The effects of ORI on pituitary-derived folliculostellate cell line (PDFS) cell viability, colony formation, proliferation ability, migration, and invasion were examined by Cell Counting Kit-8, colony formation assay, 5­Ethynyl­2'­deoxyuridine proliferation assay, wound-healing assay, and Transwell assay. The differentially expressed genes in the control and ORI-treated groups were screened by transcriptome sequencing analysis and analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment. Cell cycle analysis was performed to detect changes in cell cycle. Annexin V-fluorescein isothiocyanate/propidium iodide staining was performed to detect apoptosis in ORI-treated cells. Western blot assay was performed to detect Bax, Bcl-2, and cleaved Caspase-3 protein expression. ORI inhibited PDFS cell viability and significantly suppressed cell proliferation, migration, and invasion. GO and KEGG results showed that ORI was associated with signaling pathways such as cell cycle and apoptosis in PDFS cells. In addition, ORI blocked cells in G2/M phase and induced apoptosis in PDFS cells. ORI can trigger cell cycle disruption and apoptosis collaboratively in PDFS cells, making it a promising and effective agent for NFPA therapy.

Different evolutionary patterns of TIR1/AFBs and AUX/IAAs and their implications for the morphogenesis of land plants.

BACKGROUND: The plant hormone auxin is widely involved in plant growth, development, and morphogenesis, and the TIR1/AFB and AUX/IAA proteins are closely linked to rapid auxin response and signal transmission. However, their evolutionary history, historical patterns of expansion and contraction, and changes in interaction relationships are still unknown. RESULTS: Here, we analyzed the gene duplications, interactions, and expression patterns of TIR1/AFBs and AUX/IAAs to understand their underlying mechanisms of evolution. The ratios of TIR1/AFBs to AUX/IAAs range from 4:2 in Physcomitrium patens to 6:29 in Arabidopsis thaliana and 3:16 in Fragaria vesca. Whole-genome duplication (WGD) and tandem duplication have contributed to the expansion of the AUX/IAA gene family, but numerous TIR1/AFB gene duplicates were lost after WGD. We further analyzed the expression profiles of TIR1/AFBs and AUX/IAAs in different tissue parts of Physcomitrium patens, Selaginella moellendorffii, Arabidopsis thaliana and Fragaria vesca, and found that TIR1/AFBs and AUX/IAAs were highly expressed in all tissues in P. patens, S. moellendorffii. In A. thaliana and F. vesca, TIR1/AFBs maintained the same expression pattern as the ancient plants with high expression in all tissue parts, while AUX/IAAs appeared tissue-specific expression. In F. vesca, 11 AUX/IAAs interacted with TIR1/AFBs with different interaction strengths, and the functional specificity of AUX/IAAs was related to their ability to bind TIR1/AFBs, thus promoting the development of specific higher plant organs. Verification of the interactions among TIR1/AFBs and AUX/IAAs in Marchantia polymorpha and F. vesca also showed that the regulation of AUX/IAA members by TIR1/AFBs became more refined over the course of plant evolution. CONCLUSIONS: Our results indicate that specific interactions and specific gene expression patterns both contributed to the functional diversification of TIR1/AFBs and AUX/IAAs.

Preparation of mesoporous silica nanocarriers targeting glucose-6-phosphate isomerase inhibition and application in the treatment of rheumatoid arthritis.

Glucose 6-phosphate isomerase (G6PI) is an indicator to assist in diagnosis of rheumatoid arthritis (RA) and monitor the disease. It also plays a key role in proliferating RA synovial tissues, pannus formation, and invasion and destruction of articular cartilage. In this study, we synthesized nanoparticles targeting G6PI (siG6PI-MSN) using mesoporous silica nanocarriers (MSN) and small interfering RNA (siRNA), followed by identifying the characteristics and functions, and preliminarily exploring their application in the treatment of RA in vivo with a type II collagen-induced arthritis (CIA) rat model. It showed that the synthetic functionalized carrier had a regular pore structure and a specific volume and surface area. No obvious hemolysis or toxicity of the carrier was found when its concentration was below 100 µg/ml. Cytological results in vitro suggested that siG6PI-MSN significantly inhibited G6PI expression and reduced the ability of proliferation, migration, and invasion of FLSs, compared with the siNC-MSN group. In vivo results in the CIA rat model showed that the arthritis index and degree of joint swelling among rats in the siG6PI-MSN-treatment group were significantly lower than those in the control group. Moreover, the number of FLSs in Synovium and the levels of TNF α and IL-1 ß were also significantly decreased in the siG6PI-MSN group. Histopathology of the synovial tissue and cartilage revealed siG6PI-MSN treatment significantly reduced the pathological manifestations of arthritis. In conclusion, siG6PI-MSN effectively suppresses the proliferation and invasive growth of synovial tissue and improve joint swelling and inflammatory infiltration, thereby preventing joint damage in RA. This carrier may be a new therapeutic measure for RA, with potential social and economic benefits.

Comparison of evaluation metrics of deep learning for imbalanced imaging data in osteoarthritis studies.

PURPOSE: To compare the evaluation metrics for deep learning methods that were developed using imbalanced imaging data in osteoarthritis studies. MATERIALS AND METHODS: This retrospective study utilized 2996 sagittal intermediate-weighted fat-suppressed knee MRIs with MRI Osteoarthritis Knee Score readings from 2467 participants in the Osteoarthritis Initiative study. We obtained probabilities of the presence of bone marrow lesions (BMLs) from MRIs in the testing dataset at the sub-region (15 sub-regions), compartment, and whole-knee levels based on the trained deep learning models. We compared different evaluation metrics (e.g., receiver operating characteristic (ROC) and precision-recall (PR) curves) in the testing dataset with various class ratios (presence of BMLs vs. absence of BMLs) at these three data levels to assess the model's performance. RESULTS: In a subregion with an extremely high imbalance ratio, the model achieved a ROC-AUC of 0.84, a PR-AUC of 0.10, a sensitivity of 0, and a specificity of 1. CONCLUSION: The commonly used ROC curve is not sufficiently informative, especially in the case of imbalanced data. We provide the following practical suggestions based on our data analysis: 1) ROC-AUC is recommended for balanced data, 2) PR-AUC should be used for moderately imbalanced data (i.e., when the proportion of the minor class is above 5% and less than 50%), and 3) for severely imbalanced data (i.e., when the proportion of the minor class is below 5%), it is not practical to apply a deep learning model, even with the application of techniques addressing imbalanced data issues.

The Characteristics of Isolated Bulb Celiac Disease in Children.

OBJECTIVES: Mucosal injury in celiac disease (CD) patients can be patchy, and up to 12% of CD patients can have mucosal changes limited to the duodenal bulb. Hence, recent guidelines recommend obtaining bulb biopsies in addition to distal duodenum. This study aimed to describe a cohort of children with isolated bulb CD and assess the benefit of separating bulb biopsies. METHODS: A retrospective chart review between January 2011 and January 2022 at 2 medical centers was conducted. We included children with CD who underwent endoscopy with separated biopsies from the bulb and distal duodenum. A blinded pathologist performed Marsh-Oberhuber grading on selected cases. RESULTS: We identified 224 CD patients, of which 33 (15%) had histologically confirmed isolated bulb CD. Patients with isolated bulb CD were older at diagnosis (10 vs 8 years; P = 0.03). Median anti-tissue transglutaminase immunoglobulin A (TTG IgA) level was lower in isolate bulb CD (2.8 vs 16.7 times the upper limit of normal [ULN], P < 0.001). Almost 88% (29/33) of isolated bulb CD patients had an anti-TTG IgA value of less than 10 times the ULN. Time to anti-TTG IgA normalization (mean 14 months) was similar between the 2 groups. A pathologist review of diagnostic biopsies could not distinguish between the bulb and distal duodenum biopsies in approximately one-third of the reviewed samples. CONCLUSIONS: Separating bulb from distal duodenum biopsies can be considered during CD diagnosis, particularly in children with anti-TTG IgA levels less than 10 times the ULN. Larger prospective cohorts are needed to decide whether isolated bulb CD is a unique cohort or an early stage of the conventional CD.

Analysis of PAT1 subfamily members in the GRAS family of upland cotton and functional characterization of GhSCL13-2A in Verticillium dahliae resistance.

KEY MESSAGE: GhSCL13-2A, a member of the PAT1 subfamily in the GRAS family, positively regulates cotton resistance to Verticillium dahliae by mediating the jasmonic acid and salicylic acid signaling pathways and accumulation of reactive oxygen species. Verticillium wilt (VW) is a devastating disease of upland cotton (Gossypium hirsutum) that is primarily caused by the soil-borne fungus Verticillium dahliae. Scarecrow-like (SCL) proteins are known to be involved in plant abiotic and biotic stress responses, but their roles in cotton defense responses are still unclear. In this study, a total of 25 GhPAT1 subfamily members in the GRAS family were identified in upland cotton. Gene organization and protein domain analysis showed that GhPAT1 members were highly conserved. GhPAT1 genes were widely expressed in various tissues and at multiple developmental stages, and they were responsive to jasmonic acid (JA), salicylic acid (SA), and ethylene (ET) signals. Furthermore, GhSCL13-2A was induced by V. dahliae infection. V. dahliae resistance was enhanced in Arabidopsis thaliana by ectopic overexpression of GhSCL13-2A, whereas cotton GhSCL13-2A knockdowns showed increased susceptibility. Levels of reactive oxygen species (ROS) and JA were also increased and SA content was decreased in GhSCL13-2A knockdowns. At the gene expression level, PR genes and SA signaling marker genes were down-regulated and JA signaling marker genes were upregulated in GhSCL13-2A knockdowns. GhSCL13-2A was shown to be localized to the cell membrane and the nucleus. Yeast two-hybrid and luciferase complementation assays indicated that GhSCL13-2A interacted with GhERF5. In Arabidopsis, V. dahliae resistance was enhanced by GhERF5 overexpression; in cotton, resistance was reduced in GhERF5 knockdowns. This study revealed a positive role of GhSCL13-2A in V. dahliae resistance, establishing it as a strong candidate gene for future breeding of V. dahliae-resistant cotton cultivars.

Non-Surgical Carpal Arch Space Augmentation for Median Nerve Decompression.

The carpal tunnel is a tightly bounded space, making the median nerve prone to compression and eventually leading to carpal tunnel syndrome. Carpal tunnel release surgery transects the transverse carpal ligament to expand the tunnel arch space, decompress the median nerve, and relieve the associated symptoms. However, the surgical procedure unavoidably disrupts essential anatomical, biomechanical and physiological functions of the wrist, potentially causing reduced grip strength, pillar pain, carpal bone instability, scar tissue formation, and perineural fibrosis. It is desirable to decompress the median nerve without surgically transecting the transverse carpal ligament. This paper is to review several approaches we have developed for nonsurgical carpal arch space augmentation (CASA), namely, radio ulnar wrist compression, muscle-ligament interaction, palmar pulling, and collagenolysis of the transverse carpal ligament. Briefly summarized is the research work on the CASA topic about theoretical considerations, in vitro and in situ experiment, computational modeling, and human subject studies with asymptomatic and carpal tunnel syndrome hands.

Spatial Relationship of the Median Nerve and Transverse Carpal Ligament in Asymptomatic Hands.

The spacing between the median nerve and transverse carpal ligament (TCL) within the carpal tunnel can potentially affect the nerve morphology. This study aimed to quantify the spatial relationship between the median nerve and transverse carpal ligament in asymptomatic hands. Twelve subjects were recruited to image the carpal tunnel using robot-assisted ultrasound. The median nerve and TCL were segmented from each image and three-dimensionally reconstructed using kinematic information from the robot. The TCL-median nerve distance, nerve cross-sectional area, circularity, and position were measured along the entirety of the nerve length within the carpal tunnel. Results were averaged at every 5% of nerve length. At the nerve length percentages of 0% (distal), 25%, 50%, 75%, and 100% (proximal), the TCL-median nerve distance (±SD) was 0.7 ± 0.4, 0.7 ± 0.2, 0.5 ± 0.2, 0.5 ± 0.2, and 0.6 ± 0.3 mm, respectively. The corresponding nerve cross-sectional area was 9.4 ± 1.9, 10.6 ± 2.6, 11.2 ± 2.1, 11.2 ± 1.7, and 9.7 ± 1.9 mm2. A one-way analysis of variance showed no significant differences between the respective percentages of nerve length for TCL-median nerve distance (p = 0.219) and cross-sectional area (p = 0.869). Significant (p < 0.0001) but weak correlations were observed between the TCL-median nerve distance with cross-sectional area (r = -0.247) and circularity (r = -0.244). This study shows that the healthy median nerve morphology is consistent along the continuous nerve length within the carpal tunnel, supporting the use of 2D imaging in the evaluation of the healthy nerve.

Ethics and governance of trustworthy medical artificial intelligence.

BACKGROUND: The growing application of artificial intelligence (AI) in healthcare has brought technological breakthroughs to traditional diagnosis and treatment, but it is accompanied by many risks and challenges. These adverse effects are also seen as ethical issues and affect trustworthiness in medical AI and need to be managed through identification, prognosis and monitoring. METHODS: We adopted a multidisciplinary approach and summarized five subjects that influence the trustworthiness of medical AI: data quality, algorithmic bias, opacity, safety and security, and responsibility attribution, and discussed these factors from the perspectives of technology, law, and healthcare stakeholders and institutions. The ethical framework of ethical values-ethical principles-ethical norms is used to propose corresponding ethical governance countermeasures for trustworthy medical AI from the ethical, legal, and regulatory aspects. RESULTS: Medical data are primarily unstructured, lacking uniform and standardized annotation, and data quality will directly affect the quality of medical AI algorithm models. Algorithmic bias can affect AI clinical predictions and exacerbate health disparities. The opacity of algorithms affects patients' and doctors' trust in medical AI, and algorithmic errors or security vulnerabilities can pose significant risks and harm to patients. The involvement of medical AI in clinical practices may threaten doctors 'and patients' autonomy and dignity. When accidents occur with medical AI, the responsibility attribution is not clear. All these factors affect people's trust in medical AI. CONCLUSIONS: In order to make medical AI trustworthy, at the ethical level, the ethical value orientation of promoting human health should first and foremost be considered as the top-level design. At the legal level, current medical AI does not have moral status and humans remain the duty bearers. At the regulatory level, strengthening data quality management, improving algorithm transparency and traceability to reduce algorithm bias, and regulating and reviewing the whole process of the AI industry to control risks are proposed. It is also necessary to encourage multiple parties to discuss and assess AI risks and social impacts, and to strengthen international cooperation and communication.

First Report of Verticillium Wilt Caused by Verticillium dahliae in Grafted Tomato in Taiwan.

Grafted tomato (Solanum lycopersicum L.) is widely used to manage soil-borne diseases (Lee et.al 2010). In Taiwan, grafting on eggplant (S. melongena L.) rootstock have been extensively used to reduce bacterial wilt in tomato production. In July 2019, wilting plants were found at a cherry tomato farm (~ 0.5 ha) located at Miaoli County. About 10% tomatoes of cv. 'Mint Shine' grafted onto the eggplant rootstock displayed wilt symptoms. Numerous leaflets with chlorosis, inter-vein yellowing, V-shaped necrotic lesions and withered leaves were observed on the affected plants. Some plants eventually wilted and died. A cut at the grafting site revealed the vascular discolorations on both scion (tomato) and rootstock (eggplant). A fungus with a compact whitish colony was consistently isolated from the symptomatic vascular tissue by using acidified potato dextrose agar (PDA) plates. Two isolates, Ve2 from eggplant and Ve4 from tomato, grown on PDA plates were characterized. Both Ve2 and Ve4 grow slowly (ca. 2.6 mm/day at 28 oC) and shared almost identical cultural and morphological characteristics. They first showed whitish mycelium and cream color in reverse within 1 week. Later, numerous microsclerotia developed evenly over the colony and the reverse color turned dark black. Microscopic observations revealed hyaline hyphae with black, elongated, irregularly spherical microsclerotia measuring 31.3 to 71.5 × 16.8 to 49.0 µm (average 50.4 × 28.5 µm) on a 3-week-old PDA culture. Abundant hyaline, single-celled, ellipsoida conidia measuring 2.7 to 4.7 × 0.9 to 3.2 µm (average 3.7 × 1.9 µm) and verticillate conidiophores were observed. The fungus was identified as Verticilium dahliae based on the consistent morphological characteristics (Hawksworth et. al 1970). To confirm the identity, the internal transcribed spacer regions of ribosomal DNA, amplified by PCR with universal primers ITS4/ITS5 (White et.al 1990), were sequenced. Both strains shared the same sequences (GenBank MZ734460; MZ736637), and BLASTn searching was 100% identical to many records of V. dahliae including an ex-epitype CBS130341. Pathogenicity was tested on 3-week-old seedlings of tomato cv. 'Bonny best' and eggplant cv. 'Longship' by a root dip method (Bhat & Subbarao 2007). Eighteen plants arranged into three replications were inoculated for each host-isolate combination, and incubated in the greenhouse at 25±3℃. The pathogenicity test was repeated two times, with the result that both isolates were pathogenic to tomato and eggplant. Both isolates induced wilt symptoms in all inoculated plants within 14 days post-inoculation (DPI). Severe leaf drop, wilting and vascular discoloration in all inoculated eggplant whereas slight yellowing and mildly stunt growth in tomato were observed at 21 DPI. Koch's postulates were fulfilled by re-isolating the same fungus from both infected tomato and eggplant. All uninoculated plants remained health and no V. dahliae was isolated from them. To our knowledge, this is the first report of V. dahliae and Verticilium wilt of grafted tomato caused by this pathogen in Taiwan. This pathogen affects over 400 plant species and has resulted in significant economic losses in many regions of world (Subbarao 2020). It is important to investigate the distribution and extent of damage caused by this emerging pathogen on Solanaceous or other crops.

Improved YOLOv3 Integrating SENet and Optimized GIoU Loss for Occluded Pedestrian Detection.

Occluded pedestrian detection faces huge challenges. False positives and false negatives in crowd occlusion scenes will reduce the accuracy of occluded pedestrian detection. To overcome this problem, we proposed an improved you-only-look-once version 3 (YOLOv3) based on squeeze-and-excitation networks (SENet) and optimized generalized intersection over union (GIoU) loss for occluded pedestrian detection, namely YOLOv3-Occlusion (YOLOv3-Occ). The proposed network model considered incorporating squeeze-and-excitation networks (SENet) into YOLOv3, which assigned greater weights to the features of unobstructed parts of pedestrians to solve the problem of feature extraction against unsheltered parts. For the loss function, a new generalized intersection over unionintersection over groundtruth (GIoUIoG) loss was developed to ensure the areas of predicted frames of pedestrian invariant based on the GIoU loss, which tackled the problem of inaccurate positioning of pedestrians. The proposed method, YOLOv3-Occ, was validated on the CityPersons and COCO2014 datasets. Experimental results show the proposed method could obtain 1.2% MR-2 gains on the CityPersons dataset and 0.7% mAP@50 improvements on the COCO2014 dataset.

Bandgap-Engineered Germanene Nanosheets as an Efficient Photodynamic Agent for Cancer Therapy.

Two-dimensional (2D) monoelemental materials (Xenes) show considerable potential in bioapplications owing to their unique 2D physicochemical features and the favored biosafety resulting from their monoelemental composition. However, the narrow band gaps of Xenes prevent their broad applications in biosensors, bioimaging and phototherapeutics. In this study, it is demonstrated that 2D germanene terminated with -H via surface chemical engineering, shows a much broadened direct band gap of 1.65 eV, which enables the material to be used as a novel inorganic photosensitizer for the photodynamic therapy of singlet oxygen. Through theoretical analysis and in vitro studies, H-germanene nanosheets demonstrate a substantially enlarged band gap and favorable biodegradability, demonstrating a substantial cancer treatment capacity. This study demonstrates the feasibility of constructing novel therapeutic photodynamic agents by surface covalent engineering for catalytic tumor therapy.