All-analog photoelectronic chip for high-speed vision tasks.

Photonic computing enables faster and more energy-efficient processing of vision data1-5. However, experimental superiority of deployable systems remains a challenge because of complicated optical nonlinearities, considerable power consumption of analog-to-digital converters (ADCs) for downstream digital processing and vulnerability to noises and system errors1,6-8. Here we propose an all-analog chip combining electronic and light computing (ACCEL). It has a systemic energy efficiency of 74.8 peta-operations per second per watt and a computing speed of 4.6 peta-operations per second (more than 99% implemented by optics), corresponding to more than three and one order of magnitude higher than state-of-the-art computing processors, respectively. After applying diffractive optical computing as an optical encoder for feature extraction, the light-induced photocurrents are directly used for further calculation in an integrated analog computing chip without the requirement of analog-to-digital converters, leading to a low computing latency of 72 ns for each frame. With joint optimizations of optoelectronic computing and adaptive training, ACCEL achieves competitive classification accuracies of 85.5%, 82.0% and 92.6%, respectively, for Fashion-MNIST, 3-class ImageNet classification and time-lapse video recognition task experimentally, while showing superior system robustness in low-light conditions (0.14 fJ µm-2 each frame). ACCEL can be used across a broad range of applications such as wearable devices, autonomous driving and industrial inspections.

Morphometric brain organization across the human lifespan reveals increased dispersion linked to cognitive performance.

The human brain is organized as segregation and integration units and follows complex developmental trajectories throughout life. The cortical manifold provides a new means of studying the brain's organization in a multidimensional connectivity gradient space. However, how the brain's morphometric organization changes across the human lifespan remains unclear. Here, leveraging structural magnetic resonance imaging scans from 1,790 healthy individuals aged 8 to 89 years, we investigated age-related global, within- and between-network dispersions to reveal the segregation and integration of brain networks from 3D manifolds based on morphometric similarity network (MSN), combining multiple features conceptualized as a "fingerprint" of an individual's brain. Developmental trajectories of global dispersion unfolded along patterns of molecular brain organization, such as acetylcholine receptor. Communities were increasingly dispersed with age, reflecting more disassortative morphometric similarity profiles within a community. Increasing within-network dispersion of primary motor and association cortices mediated the influence of age on the cognitive flexibility of executive functions. We also found that the secondary sensory cortices were decreasingly dispersed with the rest of the cortices during aging, possibly indicating a shift of secondary sensory cortices across the human lifespan from an extreme to a more central position in 3D manifolds. Together, our results reveal the age-related segregation and integration of MSN from the perspective of a multidimensional gradient space, providing new insights into lifespan changes in multiple morphometric features of the brain, as well as the influence of such changes on cognitive performance.

Single hormone or synthetic agonist induces Gs/Gi coupling selectivity of EP receptors via distinct binding modes and propagating paths.

To accomplish concerted physiological reactions, nature has diversified functions of a single hormone at at least two primary levels: 1) Different receptors recognize the same hormone, and 2) different cellular effectors couple to the same hormone-receptor pair [R.P. Xiao, Sci STKE 2001, re15 (2001); L. Hein, J. D. Altman, B.K. Kobilka, Nature 402, 181-184 (1999); Y. Daaka, L. M. Luttrell, R. J. Lefkowitz, Nature 390, 88-91 (1997)]. Not only these questions lie in the heart of hormone actions and receptor signaling but also dissecting mechanisms underlying these questions could offer therapeutic routes for refractory diseases, such as kidney injury (KI) or X-linked nephrogenic diabetes insipidus (NDI). Here, we identified that Gs-biased signaling, but not Gi activation downstream of EP4, showed beneficial effects for both KI and NDI treatments. Notably, by solving Cryo-electron microscope (cryo-EM) structures of EP3-Gi, EP4-Gs, and EP4-Gi in complex with endogenous prostaglandin E2 (PGE2)or two synthetic agonists and comparing with PGE2-EP2-Gs structures, we found that unique primary sequences of prostaglandin E2 receptor (EP) receptors and distinct conformational states of the EP4 ligand pocket govern the Gs/Gi transducer coupling selectivity through different structural propagation paths, especially via TM6 and TM7, to generate selective cytoplasmic structural features. In particular, the orientation of the PGE2 ω-chain and two distinct pockets encompassing agonist L902688 of EP4 were differentiated by their Gs/Gi coupling ability. Further, we identified common and distinct features of cytoplasmic side of EP receptors for Gs/Gi coupling and provide a structural basis for selective and biased agonist design of EP4 with therapeutic potential.

Divergent suicidal symptomatic activations converge on somato-cognitive action network in depression.

Individuals with depression have the highest lifetime prevalence of suicide attempts (SA) among mental illnesses. Numerous neuroimaging studies have developed biomarkers from task-related neural activation in depressive patients with SA, but the findings are inconsistent. Empowered by the contemporary interconnected view of depression as a neural system disorder, we sought to identify a specific brain circuit utilizing published heterogeneous neural activations. We systematically reviewed all published cognitive and emotional task-related functional MRI studies that investigated differences in the location of neural activations between depressive patients with and without SA. We subsequently mapped an underlying brain circuit functionally connecting to each experimental activation using a large normative connectome database (n = 1000). The identified SA-related functional network was compared to the network derived from the disease control group. Finally, we decoded this convergent functional connectivity network using microscale transcriptomic and chemo-architectures, and macroscale psychological processes. We enrolled 11 experimental tasks from eight studies, including depressive patients with SA (n = 147) and without SA (n = 196). The heterogeneous SA-related neural activations localized to the somato-cognitive action network (SCAN), exhibiting robustness to little perturbations and specificity for depression. Furthermore, the SA-related functional network was colocalized with brain-wide gene expression involved in inflammatory and immunity-related biological processes and aligned with the distribution of the GABA and noradrenaline neurotransmitter systems. The findings demonstrate that the SA-related functional network of depression is predominantly located at the SCAN, which is an essential implication for understanding depressive patients with SA.

Inhalable Polymeric Microparticles for Phage and Photothermal Synergistic Therapy of Methicillin-Resistant Staphylococcus aureus Pneumonia.

Acute methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is a common and serious lung infection with high morbidity and mortality rates. Due to the increasing antibiotic resistance, toxicity, and pathogenicity of MRSA, there is an urgent need to explore effective antibacterial strategies. In this study, we developed a dry powder inhalable formulation which is composed of porous microspheres prepared from poly(lactic-co-glycolic acid) (PLGA), internally loaded with indocyanine green (ICG)-modified, heat-resistant phages that we screened for their high efficacy against MRSA. This formulation can deliver therapeutic doses of ICG-modified active phages to the deep lung tissue infection sites, avoiding rapid clearance by alveolar macrophages. Combined with the synergistic treatment of phage therapy and photothermal therapy, the formulation demonstrates potent bactericidal effects in acute MRSA pneumonia. With its long-term stability at room temperature and inhalable characteristics, this formulation has the potential to be a promising drug for the clinical treatment of MRSA pneumonia.

Singlet oxygen induces cell wall thickening and stomatal density reducing by transcriptome reprogramming.

Singlet oxygen (1O2) has a very short half-life of 10-5 s; however, it is a strong oxidant that causes growth arrest and necrotic lesions on plants. Its signaling pathway remains largely unknown. The Arabidopsis flu (fluorescent) mutant accumulates a high level of 1O2 and shows drastic changes in nuclear gene expression. Only two plastid proteins, EX1 (executer 1) and EX2 (executer 2), have been identified in the singlet oxygen signaling. Here, we found that the transcription factor abscisic acid insensitive 4 (ABI4) binds the promoters of genes responsive to 1O2-signals. Inactivation of the ABI4 protein in the flu/abi4 double mutant was sufficient to compromise the changes of almost all 1O2-responsive-genes and rescued the lethal phenotype of flu grown under light/dark cycles, similar to the flu/ex1/ex2 triple mutant. In addition to cell death, we reported for the first time that 1O2 also induces cell wall thickening and stomatal development defect. Contrastingly, no apparent growth arrest was observed for the flu mutant under normal light/dim light cycles, but the cell wall thickening (doubled) and stomatal density reduction (by two-thirds) still occurred. These results offer a new idea for breeding stress tolerant plants.

A form of muscular dystrophy associated with pathogenic variants in JAG2.

JAG2 encodes the Notch ligand Jagged2. The conserved Notch signaling pathway contributes to the development and homeostasis of multiple tissues, including skeletal muscle. We studied an international cohort of 23 individuals with genetically unsolved muscular dystrophy from 13 unrelated families. Whole-exome sequencing identified rare homozygous or compound heterozygous JAG2 variants in all 13 families. The identified bi-allelic variants include 10 missense variants that disrupt highly conserved amino acids, a nonsense variant, two frameshift variants, an in-frame deletion, and a microdeletion encompassing JAG2. Onset of muscle weakness occurred from infancy to young adulthood. Serum creatine kinase (CK) levels were normal or mildly elevated. Muscle histology was primarily dystrophic. MRI of the lower extremities revealed a distinct, slightly asymmetric pattern of muscle involvement with cores of preserved and affected muscles in quadriceps and tibialis anterior, in some cases resembling patterns seen in POGLUT1-associated muscular dystrophy. Transcriptome analysis of muscle tissue from two participants suggested misregulation of genes involved in myogenesis, including PAX7. In complementary studies, Jag2 downregulation in murine myoblasts led to downregulation of multiple components of the Notch pathway, including Megf10. Investigations in Drosophila suggested an interaction between Serrate and Drpr, the fly orthologs of JAG1/JAG2 and MEGF10, respectively. In silico analysis predicted that many Jagged2 missense variants are associated with structural changes and protein misfolding. In summary, we describe a muscular dystrophy associated with pathogenic variants in JAG2 and evidence suggests a disease mechanism related to Notch pathway dysfunction.

Impact of Surface Chemistry on Emulsion-Electrode Interactions and Electron-Transfer Kinetics in the Single-Entity Electrochemistry.

Single-entity electrochemistry (SEE) provides powerful means to track a single particle, single cell, and even single molecule from the nano to microscale. The electrode serves as not only the detector of collision but also the surface supplier in SEE, and the fundamental understanding of the electrode surface chemistry on the dynamic particle-electrode interactions and electrochemical responses of a single particle still remains unexplored, particularly for soft particles. Herein, dynamic interactions of microemulsions and the interaction-controlled electron-transfer (ET) kinetics are studied employing SEE and fluorescence spectroscopy. The o/w-type nitrobenzene emulsions were prepared with the surfactant-type room temperature ionic liquids (RTILs). Biased the electrode potential for the reduction of 7,7,8,8-tetracyanoquinodimethane within emulsions, it is surprising to see the distinct collision current signals on the carbon fiber ultramicroelectrode (C UME) and Au ultramicroelectrode (Au UME) in the late stage of chronoamperometric measurements. Theoretical understanding was made to determine the ET kinetics behind the disparate current signals. It is believed that the electrode surface chemistry, i.e., the surface energy, has a great influence on the dynamic emulsion-electrode interactions and ET kinetics. On the hydrophilic surface of Au UME, emulsions tend to decompose/detach from the electrode surface immediately after colliding. In contrast, on the lipophilic surface of C UME with lower surface energy, a layer of oil phase accumulated by the coalescence of emulsions and the migration of the precedent colliding emulsions, which would serve as a barrier to block ET via tunneling as manifested by the gradual slowdown of ET rate and the reduced collision frequency in the late stage of measurement. The impacts of the emulsion size and amphiphilicity of RTILs on the C UME-emulsion interactions and ET kinetics were also investigated.

In Situ Quantitative Imaging of Plasma Membrane Stiffness in Live Cells Using a Genetically Encoded FRET Sensor.

Cell membrane stiffness is critical for cellular function, with cholesterol and sphingomyelin as pivot contributors. Current methods for measuring membrane stiffness are often invasive, ex situ, and slow in process, prompting the need for innovative techniques. Here, we present a fluorescence resonance energy transfer (FRET)-based protein sensor designed to address these challenges. The sensor consists of two fluorescent units targeting sphingomyelin and cholesterol, connected by a linker that responds to the proximity of these lipids. In rigid membranes, cholesterol and sphingomyelin are in close proximity, leading to an increased FRET signal. We utilized this sensor in combination with confocal microscopy to explore changes in plasma membrane stiffness under various conditions, including differences in osmotic pressure, the presence of reactive oxygen species (ROS) and variations in substrate stiffness. Furthermore, we explored the impact of SARS-CoV-2 on membrane stiffness and the distribution of ACE2 after attachment to the cell membrane. This tool offers substantial potential for future investigations in the field of mechanobiology.

Role of TFEB-autophagy lysosomal pathway in palmitic acid induced renal tubular epithelial cell injury.

Lysosomal dysfunction and impaired autophagic flux are involved in the pathogenesis of lipotoxicity in the kidney. Here, we investigated the role of transcription factor EB (TFEB), a master regulator of autophagy-lysosomal pathway, in palmitic acid induced renal tubular epithelial cells injury. We examined lipid accumulation, autophagic flux, expression of Ps211-TFEB, and nuclear translocation of TFEB in HK-2 cells overloaded with palmitic acid (PA). By utilizing immunohistochemistry, we detected TFEB expression in renal biopsy tissues from patients with diabetic nephropathy and normal renal tissue adjacent to surgically removed renal carcinoma (controls), as well as kidney tissues from rat fed with high-fat diet (HFD) and low-fat diet (LFD). We found significant lipid accumulation, increased apoptosis, accompanied with elevated Ps211-TFEB, decreased nuclear TFEB, reduced lysosome biogenesis and insufficient autophagy in HK-2 cells treated with PA. Kidney tissues from patients with diabetic nephropathy had lower nuclear and total levels of TFEB than that in control kidney tissues. Level of renal nuclear TFEB in HFD rats was also lower than that in LFD rats. Exogenous overexpression of TFEB increased the nuclear TFEB level in HK-2 cells treated with PA, promoted lysosomal biogenesis, improved autophagic flux, reduced lipid accumulation and apoptosis. Our results collectively indicate that PA is a strong inducer for TFEB phosphorylation modification at ser211 accompanied with lower nuclear translocation of TFEB. Impairment of TFEB-mediated lysosomal biogenesis and function by palmitic acid may lead to insufficient autophagy and promote HK-2 cells injury.

Harnessing Natural Evaporation for Electricity Generation using MOF-Based Nanochannels.

Functionalized nanochannels can convert environmental thermal energy into electrical energy by driving water evaporation. This process involves the interaction between the solid-liquid interface and the natural water evaporation. The evaporation-driven water potential effect is a novel green environmental energy capture technology that has a wide range of applications and does not depend on geographical location or environmental conditions, it can generate power as long as there is water, light, and heat. However, suitable materials and structures are needed to harness this natural process for power generation. MOF materials are an emerging field for water evaporation power generation, but there are still many challenges to overcome. This work uses MOF-801, which has high porosity, charged surface, and hydrophilicity, to enhance the output performance of evaporation-driven power generation. It can produce an open circuit voltage of ≈2.2 V and a short circuit current of ≈1.9 µA. This work has a simple structure, easy preparation, low-cost and readily available materials, and good stability. It can operate stably in natural environments with high practical value.

Quality Evaluation of Guidelines for the Diagnosis and Treatment of Liver Failure.

OBJECTIVES: This study aimed to systematically assess the methodological quality and key recommendations of the guidelines for the diagnosis and treatment of liver failure (LF), furnishing constructive insights for guideline developers and equipping clinicians with evidence-based information to facilitate informed decision-making. DATA SOURCES: Electronic databases and manual searches from January 2011 to August 2023. STUDY SELECTION: Two reviewers independently screened titles and abstracts, then full texts for eligibility. Fourteen guidelines were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted data and checked by two others. Methodological quality of the guidelines was appraised using the Appraisal of Guidelines for Research and Evaluation II tool. Of the 14 guidelines, only the guidelines established by the Society of Critical Care Medicine and the American College of Gastroenterology (2023) achieved an aggregate quality score exceeding 60%, thereby meriting clinical recommendations. It emerged that there remains ample room for enhancement in the quality of the guidelines, particularly within the domains of stakeholder engagement, rigor, and applicability. Furthermore, an in-depth scrutiny of common recommendations and supporting evidence drawn from the 10 adult LF guidelines unveiled several key issues: controversy exists in the recommendation, the absence of supporting evidence and confusing use of evidence for recommendations, and a preference in evidence selection. CONCLUSIONS: There are high differences in methodological quality and recommendations among LF guidelines. Improving these existing problems and controversies will benefit existing clinical practice and will be an effective way for developers to upgrade the guidelines.

An atypical two-component system, AtcR/AtcK, simultaneously regulates the biosynthesis of multiple secondary metabolites in Streptomyces bingchenggensis.

Streptomyces bingchenggensis is an industrial producer of milbemycins, which are important anthelmintic and insecticidal agents. Two-component systems (TCSs), which are typically situated in the same operon and are composed of a histidine kinase and a response regulator, are the predominant signal transduction pathways involved in the regulation of secondary metabolism in Streptomyces. Here, an atypical TCS, AtcR/AtcK, in which the encoding genes (sbi_06838/sbi_06839) are organized in a head-to-head pair, was demonstrated to be indispensable for the biosynthesis of multiple secondary metabolites in S. bingchenggensis. With the null TCS mutants, the production of milbemycin and yellow compound was abolished but nanchangmycin was overproduced. Transcriptional analysis and electrophoretic mobility shift assays showed that AtcR regulated the biosynthesis of these three secondary metabolites by a MilR3-mediated cascade. First, AtcR was activated by phosphorylation from signal-triggered AtcK. Second, the activated AtcR promoted the transcription of milR3. Third, MilR3 specifically activated the transcription of downstream genes from milbemycin and yellow compound biosynthetic gene clusters (BGCs) and nanR4 from the nanchangmycin BGC. Finally, because NanR4 is a specific repressor in the nanchangmycin BGC, activation of MilR3 downstream genes led to the production of yellow compound and milbemycin but inhibited nanchangmycin production. By rewiring the regulatory cascade, two strains were obtained, the yield of nanchangmycin was improved by 45-fold to 6.08 g/L and the production of milbemycin was increased twofold to 1.34 g/L. This work has broadened our knowledge on atypical TCSs and provided practical strategies to engineer strains for the production of secondary metabolites in Streptomyces.IMPORTANCEStreptomyces bingchenggensis is an important industrial strain that produces milbemycins. Two-component systems (TCSs), which consist of a histidine kinase and a response regulator, are the predominant signal transduction pathways involved in the regulation of secondary metabolism in Streptomyces. Coupled encoding genes of TCSs are typically situated in the same operon. Here, TCSs with encoding genes situated in separate head-to-head neighbor operons were labeled atypical TCSs. It was found that the atypical TCS AtcR/AtcK played an indispensable role in the biosynthesis of milbemycin, yellow compound, and nanchangmycin in S. bingchenggensis. This atypical TCS regulated the biosynthesis of specialized metabolites in a cascade mediated via a cluster-situated regulator, MilR3. Through rewiring the regulatory pathways, strains were successfully engineered to overproduce milbemycin and nanchangmycin. To the best of our knowledge, this is the first report on atypical TCS, in which the encoding genes of RR and HK were situated in separate head-to-head neighbor operons, involved in secondary metabolism. In addition, data mining showed that atypical TCSs were widely distributed in actinobacteria.

Research on ultraviolet-visible composite optical target simulation technology.

This study proposes an ultraviolet-visible composite optical target simulation technique based on a liquid crystal display (LCD) spatial light modulation device to solve the problem of not being able to satisfy the demand for optical target simulation for both ultraviolet and visible light operating spectral ranges in a single system when composite simulation of multi-source spatial targets is performed. We establish a composite light source model of an ultraviolet light emitting diode (LED) and a xenon lamp to enhance the energy simulation of the ultraviolet portion, and the light is mixed and homogenized by an integrating sphere. We analyze the light transmission principle of LCD display devices and derive the equation for the relationship between its working band and transmittance. We design a transmission-type projection system with a wide spectral range and simulate the transmittance of the whole system, and demonstrate the optical target simulator can realize the simulation requirements of a wide working spectral range, high interstellar angular distance accuracy, and high magnitude accuracy.

Simulation method for multi-source information fusion space target.

Current space target simulation systems suffer from limitations, such as a single simulated spectral band, inability to allocate spectral ratios between bands, and poor imaging quality of multi-spectral simulated images. We propose a multi-source information fusion spatial target simulation method system that features a "series-parallel" hybrid connection. We optimize the design of a multi-spectral common aperture optical system and experimentally verify the proposed method. The experimental results show that the proposed system can simulate a wide range of spectral bands ranging from ultraviolet to long-wave infrared. Furthermore, it achieves precise control over the ratio of simulated radiant energy among spectral bands, with a spectral simulation error of less than 4.8%. Notably, it effectively images stars against the cosmic background and spacecraft across different spectral bands. This system serves as a theoretical cornerstone and provides crucial technological support for performance testing and rapid iterative development of multi-source information fusion space exploration systems.

Disease burden, management strategies, and unmet needs in α-thalassemia due to hemoglobin H disease.

Alpha-thalassemia is an inherited blood disorder caused by impaired α-globin chain production, leading to anemia and other complications. Hemoglobin H (HbH) disease is caused by a combination of mutations generally affecting the expression of three of four α-globin alleles; disease severity is highly heterogeneous, largely driven by genotype. Notably, non-deletional mutations cause a greater degree of ineffective erythropoiesis and hemolysis, higher transfusion burden, and increased complication risks versus deletional mutations. There are limited treatment options for HbH disease, and effective therapies are needed. This review discusses the pathophysiology of HbH disease, current management strategies, unmet needs, and emerging treatment options.

Feasibility of 18F-DOPA and 18F-FDG PET/CT for guiding decision-making for localized incidental neuroblastoma in infants under 18 months of age.

BACKGROUND: Neuroblastoma varies widely in risk. Risk indicators in infants with incidental neuroblastoma refine treatment confidence for observation or intervention. The potential of functional imaging, particularly PET/CT, remains to be defined. PROCEDURE: A retrospective review of infants under 18 months diagnosed with incidental neuroblastoma from 2008 to May 2022 in our institute was conducted. Before October 2015, incidental patients were treated similarly to symptomatic cases, undergoing biopsy or surgical excision upon diagnosis (early cohort). Post October 2015 (late cohort), treatment decisions were guided by PET/CT findings, with 18F-DOPA PET/CT confirming diagnosis and staging. For tumors with low 18F-FDG uptake, an expectant observation approach was considered. Patient characteristics, diagnostic methods, image findings at diagnosis, treatment courses, and responses were compared between cohorts. RESULTS: Thirty infants less than 18 months were identified with incidental neuroblastoma and completed PET/CT at diagnosis. The early and late cohorts each comprised 15 patients. In the late cohort, nine out of 15 patients (60%) presented with localized FDG non-avid tumors were offered the option of expectant observation. Of these, seven patients opted for observation, thereby avoiding surgery. Treatment outcomes were comparable between early and late cohorts, except for one mortality of a patient who, despite showing 18F-FDG activity, declined treatment. CONCLUSIONS: This study demonstrates the potential utility of 18F-DOPA and 18F-FDG PET/CT scans in aiding clinical decision-making for infants with localized, incidental neuroblastoma. Given the concerns regarding radiation exposure, such imaging may be valuable for cases with suspected metastasis, initial large tumor size, or growth during follow-up.

Higher tumor mutational burden is associated with inferior outcomes among pediatric patients with neuroblastoma.

INTRODUCTION: Neuroblastoma is a pediatric malignancy with heterogeneous clinical outcomes. Our aim was to identify prognostic genetic markers for patients with neuroblastoma, who were treated with the Taiwan Pediatric Oncology Group (TPOG) neuroblastoma N2002 protocol, to improve risk stratification and inform treatment. METHODS: Our analysis was based on 53 primary neuroblastoma specimens, diagnosed pre-chemotherapy, and 11 paired tumor relapse specimens. Deep sequencing of 113 target genes was performed using a custom panel. Multiplex ligation-dependent probe amplification was performed to identify clinical outcomes related to copy-number variations. RESULTS: We identified 128 variations associated with survival, with the number of variations being higher in the relapse than that in the diagnostic specimen (p = .03). The risk of event and mortality was higher among patients with a tumor mutational burden ≥10 than that in patients with a lower burden (p < .0001). Multivariate analysis identified tumor mutational burden, MYCN amplification, and chromosome 3p deletion as significant prognostic factors, independent of age at diagnosis, sex, and tumor stage. The 5-year event-free survival and overall survival rate was lower among patients with high tumor burden than in patients with low tumor burden. Furthermore, there was no survival of patients with an ALK F1147L variation at 5 years after diagnosis. CONCLUSIONS: Genome sequencing to determine the tumor mutational burden and ALK variations can improve the risk classification of neuroblastoma and inform treatment.

Tea polyphenols alleviate TBBPA-induced inflammation, ferroptosis and apoptosis via TLR4/NF-κB pathway in carp gills.

The extensive application of Tetrabromobisphenol A (TBBPA) leads to the pollution of part of the water environment and brings great safety risks to aquatic animals. As a natural extract, tea polyphenols (TPs) have antioxidant and anti-inflammatory effects. Gills are one of the immune organs of fish and constitute the first line of defense of the immune system. However, it was unclear whether TPs could mitigate TBBPA-induced gills injury. Therefore, an animal model was established to investigate the effect of TPs on TBBPA-induced gills. The results indicated that TBBPA changed the coefficient and tissue morphology of carp gills. In addition, TBBPA induced oxidative stress and inflammation, leading to ferroptosis and apoptosis in carp gills. Dietary addition of TPs significantly improved the antioxidant capacity of carp, effectively inhibited the overexpression of TLR4/NF-κB and its mediated inflammatory response. Moreover, TPs restored iron metabolism, reduced the expression of pro-apoptotic factors thereby alleviating ferroptosis and apoptosis in carp gills. This study enriched the protective effect of TPs and provided a new way to improve the innate immunity of carp.

An inflammation-based model for identifying severe acute pancreatitis: a single-center retrospective study.

BACKGROUND AND AIMS: Severe acute pancreatitis (SAP) is potentially lethal. Considering the role of inflammation in the progression of acute pancreatitis (AP), this study aims to develop a model based on inflammatory indexes for identifying the presence of SAP. METHODS: Overall, 253 patients with AP who were consecutively admitted between July 2018 and November 2020 were screened, of whom 60 had SAP. Systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-platelet ratio (NPR), systemic inflammation response index (SIRI), platelet-to-albumin ratio (PAR), C-reactive protein-to-albumin ratio (CAR), C-reactive protein-to-lymphocyte ratio (CLR), and triglyceride glucose (TyG) index were calculated. Multivariate logistic regression analyses were performed to identify independent risk factors of SAP. Then, inflammation-based models were established. Receiver operating characteristics (ROC) curve analyses were performed. Area under ROC curve (AUROC) was calculated. RESULTS: Diabetes mellitus, fatty liver, high white blood cell count (WBC), C-reactive protein (CRP), red blood cell distribution width (RDW), procalcitonin (PCT), SII, NLR, NPR, CAR, CLR, and TyG index, and a low LMR were significantly associated with SAP. Considering the collinearity among these variables, 10 multivariate logistic regression analyses were separately performed. Finally, four independent inflammation-based models were established. Of them, the best one, which was calculated as follows: 1.204*fatty liver (yes = 1; no = 0) + 0.419*PCT + 0.005*CLR - 2.629, had an AUROC of 0.795 with a specificity of 73.4% and a sensitivity of 71.7%. CONCLUSION: The inflammation-based model consisting of fatty liver, PCT, and CLR has a good diagnostic performance for SAP.