Fibrosis induced by resident macrophages has divergent roles in pancreas inflammatory injury and PDAC.

Tissue-resident macrophages (TRMs) are long-lived cells that maintain locally and can be phenotypically distinct from monocyte-derived macrophages. Whether TRMs and monocyte-derived macrophages have district roles under differing pathologies is not understood. Here, we showed that a substantial portion of the macrophages that accumulated during pancreatitis and pancreatic cancer in mice had expanded from TRMs. Pancreas TRMs had an extracellular matrix remodeling phenotype that was important for maintaining tissue homeostasis during inflammation. Loss of TRMs led to exacerbation of severe pancreatitis and death, due to impaired acinar cell survival and recovery. During pancreatitis, TRMs elicited protective effects by triggering the accumulation and activation of fibroblasts, which was necessary for initiating fibrosis as a wound healing response. The same TRM-driven fibrosis, however, drove pancreas cancer pathogenesis and progression. Together, these findings indicate that TRMs play divergent roles in the pathogenesis of pancreatitis and cancer through regulation of stromagenesis.

Heat-assisted detection and ranging.

Machine perception uses advanced sensors to collect information about the surrounding scene for situational awareness1-7. State-of-the-art machine perception8 using active sonar, radar and LiDAR to enhance camera vision9 faces difficulties when the number of intelligent agents scales up10,11. Exploiting omnipresent heat signal could be a new frontier for scalable perception. However, objects and their environment constantly emit and scatter thermal radiation, leading to textureless images famously known as the 'ghosting effect'12. Thermal vision thus has no specificity limited by information loss, whereas thermal ranging-crucial for navigation-has been elusive even when combined with artificial intelligence (AI)13. Here we propose and experimentally demonstrate heat-assisted detection and ranging (HADAR) overcoming this open challenge of ghosting and benchmark it against AI-enhanced thermal sensing. HADAR not only sees texture and depth through the darkness as if it were day but also perceives decluttered physical attributes beyond RGB or thermal vision, paving the way to fully passive and physics-aware machine perception. We develop HADAR estimation theory and address its photonic shot-noise limits depicting information-theoretic bounds to HADAR-based AI performance. HADAR ranging at night beats thermal ranging and shows an accuracy comparable with RGB stereovision in daylight. Our automated HADAR thermography reaches the Cramér-Rao bound on temperature accuracy, beating existing thermography techniques. Our work leads to a disruptive technology that can accelerate the Fourth Industrial Revolution (Industry 4.0)14 with HADAR-based autonomous navigation and human-robot social interactions.

Runx3 specifies lineage commitment of innate lymphoid cells.

Subsets of innate lymphoid cells (ILCs) reside in the mucosa and regulate immune responses to external pathogens. While ILCs can be phenotypically classified into ILC1, ILC2 and ILC3 subsets, the transcriptional control of commitment to each ILC lineage is incompletely understood. Here we report that the transcription factor Runx3 was essential for the normal development of ILC1 and ILC3 cells but not of ILC2 cells. Runx3 controlled the survival of ILC1 cells but not of ILC3 cells. Runx3 was required for expression of the transcription factor RORγt and its downstream target, the transcription factor AHR, in ILC3 cells. The absence of Runx3 in ILCs exacerbated infection with Citrobacter rodentium. Therefore, our data establish Runx3 as a key transcription factor in the lineage-specific differentiation of ILC1 and ILC3 cells.

AAV-mediated gene-replacement therapy restores viability of BCD patient iPSC derived RPE cells and vision of Cyp4v3 knockout mice.

Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessive retinal degenerative disease characterized by yellow-white crystal deposits in the posterior pole, degeneration of the retinal pigment epithelium (RPE), and sclerosis of the choroid. Mutations in the cytochrome P450 4V2 gene (CYP4V2) cause BCD, which is associated with lipid metabolic disruption. The use of gene-replacement therapy in BCD has been hampered by the lack of disease models. To advance CYP4V2 gene-replacement therapy, we generated BCD patient-specific induced pluripotent stem cell (iPSC)-RPE cells and Cyp4v3 knockout (KO) mice as disease models and AAV2/8-CAG-CYP4V2 as treatment vectors. We demonstrated that after adeno-associated virus (AAV)-mediated CYP4V2 gene-replacement therapy BCD-iPSC-RPE cells presented restored cell survival and reduced lipid droplets accumulation; restoration of vision in Cyp4v3 KO mice was revealed by elevated electroretinogram amplitude and ameliorated RPE degeneration. These results suggest that AAV-mediated gene-replacement therapy in BCD patients is a promising strategy.

Screening copy number variations in 35 unsolved inherited retinal disease families.

The purpose of this study was to screen Copy Number Variations (CNVs) in 35 unsolved Inherited Retinal Dystrophy (IRD) families. Initially, next generation sequencing, including a specific Hereditary Eye Disease Enrichment Panel or Whole exome sequencing, was employed to screen (likely) pathogenic Single-nucleotide Variants (SNVs) and small Insertions and Deletions (indels) for these cases. All available SNVs and indels were further validated and co-segregation analyses were performed in available family members by Sanger sequencing. If not, after excluding deep intronic variants, Multiplex ligation-dependent probe amplification (MLPA), quantitative fluorescence PCR (QF-PCR) and Sanger sequencing were employed to screen CNVs. We determined that 18 probands who had heterozygous SNVs/indels or whose parents were not consanguineous but had homozygous SNVs/indels in autosomal recessive IRDs genes had CNVs in another allele of these genes, 11 families had disease-causing hemizygous CNVs in X-linked IRD genes, 6 families had (likely) pathogenic heterozygous CNVs in PRPF31 gene. Of 35 families, 33 different CNVs in 16 IRD-associated genes were detected, with PRPF31, EYS and USH2A the most common disease-causing gene in CNVs. Twenty-six and 7 of them were deletion and duplication CNVs, respectively. Among them, 14 CNVs were first reported in this study. Our research indicates that CNVs contribute a lot to IRDs, and screening of CNVs substantially increases the diagnostic rate of IRD. Our results emphasize that MLPA and QF-PCR are ideal methods to validate CNVs, and the novel CNVs reported herein expand the mutational spectrums of IRDs.

Spexin acts as a novel glucose-lowering factor in grass carp (Ctenopharyngodon idella).

At present, the physiological roles of various hormones in fish glucose metabolism have been elucidated. Spexin, a 14-amino acids polypeptide, is highly conserved in many species and has functions such as reducing body weight and improving insulin resistance. In this paper, the open reading frame (ORF) of spx21 in grass carp (Ctenopharyngodon idella) was cloned, and the tissue distribution of spx1 and spx2, their direct and indirect regulatory effects on glucose metabolism of grass carp were investigated. The ORF of spx2 gene in grass carp was 279 bp in length. Moreover, spx1 was highly expressed in the adipose tissue, while spx2 was highly expressed in the brain. In vitro, SPX1 and SPX2 showed opposite effects on the glycolytic pathway in the primary hepatocytes. In vivo, intraperitoneal injection of SPX1 and SPX2 significantly reduced serum glucose levels and increased hepatopancreas glycogen contents. Meanwhile, SPX1 and SPX2 promoted the expression of key genes of glycolysis (pk) and glycogen synthesis (gys) in the hepatopancreas at 3 h post injection. As for indirect effects, 1000 nM SPX1 and SPX2 significantly increased insulin-mediated liver type phosphofructokinase (pfkla) mRNA expression and enhanced the inhibitory effects of insulin on glucose-6-phosphatase (g6pase), phosphoenolpyruvate carboxykinase (pepck), glycogen phosphorylase L (pygl) mRNA expression. Our results show that SPX1 and SPX2 have similar indirect effects on the regulation of glucose metabolism that enhance insulin activity, but they exhibit opposite roles in terms of direct effects.

FOS-Mediated PLCB1 Induces Radioresistance and Weakens the Antitumor Effects of CD8+ T Cells in Triple-Negative Breast Cancer.

Radioresistance and immune evasion are interactive and crucial events leading to treatment failure and progression of human malignancies. This research studies the role of phospholipase C beta 1 (PLCB1) in these events in triple-negative breast cancer (TNBC) and the regulatory mechanism. PLCB1 was bioinformatically predicted as a dysregulated gene potentially linked to radioresistance in TNBC. Parental TNBC cell lines were exposed to fractionated radiation for 6 weeks. PLCB1 expression was decreased in the first 2 weeks but gradually increased from Week 3. PLCB1 knockdown increased the radiosensitivity of the cells, as manifested by a decreased half-inhibitory dose of irradiation, reduced cell proliferation, apoptosis resistance, mobility, and tumorigenesis in mice. The FOS transcription factor promoted PLCB1 transcription and activated the PI3K/AKT signaling. Knockdown of FOS similarly reduced radioresistance and T cells-mediated immune evasion. However, the radiosensitivity of TNBC cells and the antitumor effects of CD8+ T cells could be affected by a PI3K/AKT activator or by the PLCB1 upregulation. The PLCB1 or FOS knockdown also suppressed radioresistance and tumorigenesis of the TNBC cells in mice. In conclusion, FOS-mediated PLCB1 induces radioresistance and weakens the antitumor effects of CD8+ T cells in TNBC by activating the PI3K/AKT signaling pathway.

Peripheral Nerve Injury Induced by Japanese Encephalitis Virus in C57BL/6 Mouse.

Japanese encephalitis virus (JEV), with neurotoxic and neuroinvasive properties, is the major cause of human viral encephalitis in Asia. Although Guillain-Barré syndrome caused by JEV infections is not frequent, a few cases have been reported in recent years. To date, no existing animal model for JEV-induced peripheral nerve injury (PNI) has been established, and thus the pathogenic mechanism is not clarified. Therefore, an animal model is urgently required to clarify the correlation between JEV infection and PNI. In the present study, we used JEV GIb strain of NX1889 to establish a mouse model of JEV infection. The general neurological signs emerged on day 3 of modeling. The motor function continued to deteriorate, reaching a maximum at 8 to 13 days postinfection (dpi) and gradually recovered after 16 dpi. The injuries of 105 PFU and 106 PFU groups were the most severe. Transmission electron microscopy and immunofluorescence staining showed varying degrees of demyelination and axonal degeneration in the sciatic nerves. The electrophysiological recordings demonstrated the presence of demyelinating peripheral neuropathy with reduced nerve conduction velocity. The decreased amplitudes and the prolonged end latency revealed axonal-type motor neuropathy. Demyelination is predominant in the early stage, followed by axonal injury. The expression level of JEV-E protein and viral RNA was elevated in the injured sciatic nerves, suggesting that it may cause PNI at the early stage. Inflammatory cell infiltration and increased inflammatory cytokines indicated that neuroinflammation is involved in JEV-induced PNI. IMPORTANCE JEV is a neurotropic flavivirus belonging to the Flaviviridae family and causes high mortality and disability rates. It invades the central nervous system and induces acute inflammatory injury and neuronal death. Thus, JEV infection is a major global public health concern. Previously, motor dysfunction was mainly attributed to central nervous system damage. Our knowledge regarding JEV-induced PNI is vague and neglected. Therefore, a laboratory animal model is essential. Herein, we showed that C57BL/6 mice can be used to study JEV-induced PNI through multiple approaches. We also demonstrated that viral loads might be positively correlated with lesion severity. Therefore, inflammation and direct virus infection may be the putative mechanisms underlying JEV-induced PNI. The results of this study laid the foundation for further elucidation of the pathogenesis mechanisms of PNI caused by JEV.

First-in-Human Evaluation of [18F]FDOPA Produced by Organo-Photoredox Reactions.

Photoredox is a powerful synthetic tool in organic chemistry and has been widely used in various fields, including nuclear medicine and molecular imaging. In particular, acridinium-based organophotoredox radiolabeling has significantly impacted the production and discovery of positron emission tomography (PET) agents. Despite their extensive use in preclinical research, no PET agents synthesized by acridinium photoredox labeling have been tested in humans. [18F]FDOPA is clinically used for tumor diagnosis and the evaluation of neuropsychiatric disorders, but its application is limited by complex synthesis methods, the need for expensive modules, and/or the high cost of consumable materials/cassettes. In this report, we integrated a photoredox labeling unit with an automated module and produced [18F]FDOPA for human study. This research not only represents the first human study of a PET agent generated by acridinium-based organophotoredox reactions but also demonstrates the safety of this novel labeling method, serving as a milestone/reference for the clinical translation of other PET agents generated by this technique in the future.

Can we skip invasive biopsy of sentinel lymph nodes? A preliminary investigation to predict sentinel lymph node status using PET/CT-based radiomics.

BACKGROUND: Sentinel lymph node (SLN) biopsy (SLNB) is considered the gold standard for detecting SLN metastases in patients with invasive ductal breast cancer (IDC). However, SLNB is invasive and associated with several complications. Thus, this study aimed to evaluate the diagnostic performance of a non-invasive radiomics analysis utilizing 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT) for assessing SLN metastasis in IDC patients. METHODS: This retrospective study included 132 patients with biopsy-confirmed IDC, who underwent 18F-FDG PET/CT scans prior to mastectomy or breast-conserving surgery with SLNB. Tumor resection or SLNB was conducted within one-week post-scan. Clinical data and metabolic parameters were analyzed to identify independent SLN metastasis predictors. Radiomic features were extracted from each PET volume of interest (VOI) and CT-VOI. Feature selection involved univariate and multivariate logistic regression analysis, and the least absolute shrinkage and selection operator (LASSO) method. Three models were developed to predict SLN status using the random forest (RF), decision tree (DT), and k-Nearest Neighbors (KNN) classifiers. Model performance was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: The study included 91 cases (32 SLN-positive and 59 SLN-negative patients) in the training cohort and 41 cases (29 SLN-positive and 12 SLN-negative patients) in the validation cohort. Multivariate logistic regression analysis identified Ki 67 and TLG as independent predictors of SLN status. Five PET-derived features, three CT-derived features, and two clinical variables were selected for model development. The AUC values of the RF, KNN, and DT models for the training cohort were 0.887, 0.849, and 0.824, respectively, and for the validation cohort were 0.856, 0.830, and 0.819, respectively. The RF model demonstrated the highest accuracy for the preoperative prediction of SLN metastasis in IDC patients. CONCLUSION: The PET-CT radiomics approach may offer robust and non-invasive predictors for SLN status in IDC patients, potentially aiding in the planning of personalized treatment strategies for IDC patients.

Development and validation of a preoperative CT­based radiomics nomogram to differentiate tuberculosis granulomas from lung adenocarcinomas: an external validation study.

BACKGROUND: An accurate and non-invasive approach is urgently needed to distinguish tuberculosis granulomas from lung adenocarcinomas. This study aimed to develop and validate a nomogram based on contrast enhanced-compute tomography (CE-CT) to preoperatively differentiate tuberculosis granuloma from lung adenocarcinoma appearing as solitary pulmonary solid nodules (SPSN). METHODS: This retrospective study analyzed 143 patients with lung adenocarcinoma (mean age: 62.4 ± 6.5 years; 54.5% female) and 137 patients with tuberculosis granulomas (mean age: 54.7 ± 8.2 years; 29.2% female) from two centers between March 2015 and June 2020. The training and internal validation cohorts included 161 and 69 patients (7:3 ratio) from center No.1, respectively. The external testing cohort included 50 patients from center No.2. Clinical factors and conventional radiological characteristics were analyzed to build independent predictors. Radiomics features were extracted from each CT-volume of interest (VOI). Feature selection was performed using univariate and multivariate logistic regression analysis, as well as the least absolute shrinkage and selection operator (LASSO) method. A clinical model was constructed with clinical factors and radiological findings. Individualized radiomics nomograms incorporating clinical data and radiomics signature were established to validate the clinical usefulness. The diagnostic performance was assessed using the receiver operating characteristic (ROC) curve analysis with the area under the receiver operating characteristic curve (AUC). RESULTS: One clinical factor (CA125), one radiological characteristic (enhanced-CT value) and nine radiomics features were found to be independent predictors, which were used to establish the radiomics nomogram. The nomogram demonstrated better diagnostic efficacy than any single model, with respective AUC, accuracy, sensitivity, and specificity of 0.903, 0.857, 0.901, and 0.807 in the training cohort; 0.933, 0.884, 0.893, and 0.892 in the internal validation cohort; 0.914, 0.800, 0.937, and 0.735 in the external test cohort. The calibration curve showed a good agreement between prediction probability and actual clinical findings. CONCLUSION: The nomogram incorporating clinical factors, radiological characteristics and radiomics signature provides additional value in distinguishing tuberculosis granuloma from lung adenocarcinoma in patients with a SPSN, potentially serving as a robust diagnostic strategy in clinical practice.

Thymocyte selection-associated high mobility box protein regulates T lymphocytes exhaustion in patients with myelodysplastic syndromes by inhibiting PI3K/AKT/mTOR pathway.

Myelodysplastic syndromes (MDS) patients often experience CD8+ T lymphocytes exhaustion, which plays a crucial role in the development of MDS. However, the specific role of thymocyte selection-associated high mobility box protein (TOX) in the CD8+ T lymphocytes exhaustion in MDS patients remains unclear. In this study, we investigated the role of TOX in CD8+ T lymphocytes exhaustion in patients with MDS. The expression of TOX, inhibitory receptors (IRs), and functional molecules in peripheral blood T lymphocytes of MDS patients and normal controls were detected using flow cytometry. Lentiviral transduction was used to create stable TOX-knockdown CD8+ T lymphocytes, and small interfering RNA (si-RNA) was used to knock down TOX in Jurkat cells. The expression of TOX was found to be significantly higher in CD8+ T lymphocytes of MDS patients compared to normal controls. This was associated with upregulated IRs and reduced expression of functional molecules such as Granzyme and Perforin. Myelodysplastic syndromes patients with higher TOX expression had poor clinical indicators and shorter survival. Knockdown of TOX using sh-RNA partially reverses the exhausted phenotype and enhances the lethality of CD8+ T lymphocytes. Moreover, the knockdown of TOX using si-RNA in Jurkat cells improved cell proliferation activity, down-regulated IRs and activated PI3K/AKT/mTOR signaling pathway. TOX promotes the exhaustion of CD8+ T lymphocytes by inhibiting PI3K/AKT/mTOR pathway, and targeted inhibition of TOX could partially restore the effector functions and activity of CD8+ T lymphocytes.

Sirtuins in kidney diseases: potential mechanism and therapeutic targets.

Sirtuins, which are NAD+-dependent class III histone deacetylases, are involved in various biological processes, including DNA damage repair, immune inflammation, oxidative stress, mitochondrial homeostasis, autophagy, and apoptosis. Sirtuins are essential regulators of cellular function and organismal health. Increasing evidence suggests that the development of age-related diseases, including kidney diseases, is associated with aberrant expression of sirtuins, and that regulation of sirtuins expression and activity can effectively improve kidney function and delay the progression of kidney disease. In this review, we summarise current studies highlighting the role of sirtuins in renal diseases. First, we discuss sirtuin family members and their main mechanisms of action. We then outline the possible roles of sirtuins in various cell types in kidney diseases. Finally, we summarise the compounds that activate or inhibit sirtuin activity and that consequently ameliorate renal diseases. In conclusion, targeted modulation of sirtuins is a potential therapeutic strategy for kidney diseases. Video Abstract.

Safety and efficacy of baricitinib in steroid-resistant or relapsed immune thrombocytopenia: An open-label pilot study.

Patients with steroid-resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus-associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open-label, single-arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6-month follow-up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6-20) days, and the median peak platelet count was 94 (IQR 72-128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP-modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.

Improvement of sea buckthorn (Hippophae rhamnoides L.) flavonoids on the antioxidant and immune performance of Yellow River carp (Cyprinus carpio L.) fed high-carbohydrate diet.

High-carbohydrate (HC) diets may lead to the deterioration of the antioxidant and immune properties of Yellow River carp and the healthy development of the industry. Studies in mammals have found that sea buckthorn flavonoids (SF) improve antioxidant and immune performance. Therefore, this study comprehensively evaluated the effects of SF on Yellow River carp using in vitro and feeding trials with an HC diet. Control (C, 27.23 %), high-carbohydrate (HC, 42.99 %), and HC + SF (0.1 %, 0.2 %, and 0.4 %) groups were studied in a 10-week aquaculture experiment. The main findings were as follows: (1) SF scavenged O2·-, ·OH, and DPPH free radicals in vitro, which gradually increased with the SF concentration. (2) The antioxidant and immune performance of Yellow River carp was enhanced by dietary supplementation with SF, which involved the regulation of activities of antioxidant and immune enzymes, as well as their changes at the transcription and protein levels. In terms of antioxidant properties, compared to the HC group, HC + SF significantly decreased the activities of glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase and the contents of H2O2 and malondialdehyde in the serum and hepatopancreas. The activities of glutathione, glutathione-Px, superoxide dismutase, catalase, and total antioxidant activity in the HC-diet group. In contrast, the addition of SF increased antioxidant enzyme activity. In the hepatopancreas and muscles, SF regulated and activated Nrf2-Keap1, a key signaling pathway for oxidative stress. SF significantly increased the mRNA expression levels of downstream genes (gr, ho-1, cat, and sod) regulated by nrf2. In terms of immune performance, 0.4 % SF markedly increased the activity of immune-related enzymes. SF inhibited the gene expression of pro-inflammatory factors induced by the HC diet and promoted the gene expression of anti-inflammatory factors. In addition, the resistance of Yellow River carp to Aeromonas hydrophila was enhanced by SF. In summary, SF supplementation can reduce oxidative stress and inflammatory harm caused by the HC diet and improve the antioxidant and immune performance of Yellow River carp to varying degrees.

Identification of Primary Organophosphate Esters Contributing to Enhanced Risk of Gestational Diabetes Mellitus Based on a Case-Control Study.

Epidemiological studies on associations of organophosphate ester (OPE) exposure and gestational diabetes mellitus (GDM) risk, which remain rare and inconclusive, were carried out with a case-control population comprising 287 GDM and 313 non-GDM pregnant women recruited from Tianjin. The GDM group suffered distinctly higher serum concentrations of tri-n-butyl phosphate (TNBP), tri(2-butoxyethyl) phosphate (TBOEP), triphenyl phosphate (TPHP), tri-iso-propyl phosphate (TIPP), and tri(1-chloro-2-propyl) phosphate (TCIPP) than the healthy control group (p < 0.001). Traditional analysis methods employed for either individual or mixture effects found positive correlations (p < 0.05) between the concentrations of five OPEs (i.e., TNBP, TBOEP, TPHP, TIPP, and TCIPP) and the incidence of GDM, while 2-ethylhexyl diphenyl phosphate, tri(1-chloro-2-propyl) phosphate, and bis(2-ethylhexyl) phosphate exhibited opposite effects. Three machine learning methods considering the concurrence of OPE mixture exposure and population characteristics were applied to clarify their relative importance to GDM risk, among which random forest performed the best. Several OPEs, particularly TNBP and TBOEP ranking at the top, made greater contributions than some demographical characteristics, such as prepregnancy body mass index and family history of diabetes, to the occurrence of GDM. This was further validated by another independent case-control population obtained from Hangzhou.

α-Cyanostilbene-based Molecule with the Synergistical Mechanisms of AIE, ESIPT and TICT: A New Schiff Base Probe for Selective Detection of Fe3+ and Reversible Response to HCl/NH3 Vapor.

We designed and synthesized a new Schiff base probe, which incorporated the salicylaldehyde-analogue α-cyanostilbene and benzophenone hydrazone by the imine linkage. Its chemical structure was verified by FT-IR, MALDI-TOF-MS, HR-MS and 1H/13C NMR technologies. It could exhibit a red fluorescence based on the synergistical effects of aggregation-induce emission (AIE), excited-state intramolecular proton transfer (ESIPT) and twisted intramolecular charge-transfer (TICT) in the aggregation or solid states. Interestingly, the TLC-based test strip loaded with the target compound showed the reversible fluorescence response to amine/acid vapor and on-site visual fluorescence quenching response to Fe3+. In THF/water mixtures (fw = 90%, 10 µM, pH = 7.4), the detection limit (DL) and the binding constant (Ka) of the developed probe towards Fe3+ were evaluated as 5.50 × 10- 8 M and 1.69 × 105, respectively. The developed probe was successfully applied for the detection of Fe3+ with practical, reliable, and satisfying results.

Bio-Based Copolyester PEIFT: Enhanced Hydrophilicity, Rigidity, and Applications in Nanofibers.

The raw materials of Poly(ethylene terephthalate) (PET) are derived from petroleum-based resources, which are no sustainable. Therefore, previous researchers introduced biomass-derived 2,5-tetrahydrofurfuryl dimethanol (THFDM) into PET. However, its heat resistance has decreased compared to PET. In this paper, a novel bio-based copolyester, poly(ethylene glycol-co-2,5-tetrahydrofuran dimethanol-co-isosorbide terephthalate) (PEIFT), is prepared by introducing biomass-derived isosorbide (ISB) and THFDM into the PET chains through melting copolymerization process. With the introduction of ISB content, copolyesters' hydrophilicity and rigidity improve. Compared to PET, glass transition temperature (Tg) increases by over 5 °C. In addition, the toughness and spinning performance of PEIFT have also been improved as a result of the addition of THFDM components. The hydrophobicity of PEIFTs electrospinning is greatly improved, with a contact angle exceeding 135°. Finally, due to the good hydrophobicity of PEIFTs nanofibers, they have potential application value in the manufacture of hydrophobic nanofiber and filter films. Given its biomass source and excellent performance, they make it easier to replace materials derived from petroleum.

Single amino acid variation in MAB21L1 is dominantly associated with congenital eye defects.

BACKGROUND: Diagnosis of a genetic disease and determination of the causative molecular lesion rely on the availability of the disease-associated pedigrees. Microphthalmia is a congenital eye defect due to an insufficiently developed visual system; its prevalence is 1-3 in 10 000 live births. OBJECTIVE: We analysed a pedigree exhibiting autosomal dominant inheritance of microphthalmia to determine the genetic lesion; used AlphaFold2 to predict the changes in the protein's 3-Dimensional structure; and compared wild-type and variant proteins in cultured cells or Drosophila model was used to explore the cellular or developmental function of the encoded product. RESULTS: We identified a novel missense variation, F52L, in MAB21L1 that is absent in population databases and present exclusively in the individuals diagnosed with microphthalmia in this pedigree. Common structural changes were predicted for the disease-associated variants clustered at amino acids 49-52, and these variant products were also predominantly trapped in the cytoplasm of cultured human lens epithelia. To recapitulate its dominant effect in development, we expressed the Drosophila homologue corresponding to MAB21L1F52L and caused malformation of sensory organs. CONCLUSION: Mutations at the residues 49-52 of MAB21L1 compromise eye development. We recommend including MAB21L1 in the genetic testing panel for congenital eye disorders.

Deep learning-based automatic segmentation of meningioma from T1-weighted contrast-enhanced MRI for preoperative meningioma differentiation using radiomic features.

BACKGROUND: This study aimed to establish a dedicated deep-learning model (DLM) on routine magnetic resonance imaging (MRI) data to investigate DLM performance in automated detection and segmentation of meningiomas in comparison to manual segmentations. Another purpose of our work was to develop a radiomics model based on the radiomics features extracted from automatic segmentation to differentiate low- and high-grade meningiomas before surgery. MATERIALS: A total of 326 patients with pathologically confirmed meningiomas were enrolled. Samples were randomly split with a 6:2:2 ratio to the training set, validation set, and test set. Volumetric regions of interest (VOIs) were manually drawn on each slice using the ITK-SNAP software. An automatic segmentation model based on SegResNet was developed for the meningioma segmentation. Segmentation performance was evaluated by dice coefficient and 95% Hausdorff distance. Intra class correlation (ICC) analysis was applied to assess the agreement between radiomic features from manual and automatic segmentations. Radiomics features derived from automatic segmentation were extracted by pyradiomics. After feature selection, a model for meningiomas grading was built. RESULTS: The DLM detected meningiomas in all cases. For automatic segmentation, the mean dice coefficient and 95% Hausdorff distance were 0.881 (95% CI: 0.851-0.981) and 2.016 (95% CI:1.439-3.158) in the test set, respectively. Features extracted on manual and automatic segmentation are comparable: the average ICC value was 0.804 (range, 0.636-0.933). Features extracted on manual and automatic segmentation are comparable: the average ICC value was 0.804 (range, 0.636-0.933). For meningioma classification, the radiomics model based on automatic segmentation performed well in grading meningiomas, yielding a sensitivity, specificity, accuracy, and area under the curve (AUC) of 0.778 (95% CI: 0.701-0.856), 0.860 (95% CI: 0.722-0.908), 0.848 (95% CI: 0.715-0.903) and 0.842 (95% CI: 0.807-0.895) in the test set, respectively. CONCLUSIONS: The DLM yielded favorable automated detection and segmentation of meningioma and can help deploy radiomics for preoperative meningioma differentiation in clinical practice.