Circular RNA CircZNF644 Facilitates Circulating Follicular Helper T Cells Response in Patients with Graves' Disease.

Aberrant accumulation of circulating follicular helper T cells (cTfh) has been found in the peripheral blood mononuclear cells (PBMCs) of Graves' disease (GD) patients. However, the underlying mechanism that contributes to the imbalance of cTfh cells remains unknown. Previously, studies described a GD-related circular RNAs (circRNAs)-circZNF644 that might be associated with cTfh cells. This study aimed to investigate the role of circZNF644 on cTfh cells in GD patients. Here, we found that circZNF644 was highly stable expression in the PBMCs of GD patients, which was positively correlated with the serum levels of TSH receptor autoantibodies (TRAb). Knockdown of circZNF644 caused a reduction of the proportion of cTfh cells in vitro. Mechanistically, circZNF644 served as a ceRNA for miR-29a-3p to promote ICOS expression, resulting in increased cTfh cells. In the PBMCs of GD patients, circZNF644 expression was positively correlated with ICOS expression and the percentage of cTfh cells, but negatively related to miR-29a-3p expression. Additionally, a strong relationship between circZNF644 and IL-21 was revealed in GD patients, and silencing of circZNF644 inhibited IL-21 expression. Our study elucidated that elevated expression of circZNF644 is a key feature in the development of GD and may contribute to the pathogenic role of cTfh cells in GD.

Prognostic value of systemic immune-inflammation index in patients with metastatic renal cell carcinoma treated with systemic therapy: a meta-analysis.

Objective: A novel systemic immune-inflammation index (SII), based on the neutrophils, lymphocytes, and platelet counts, is associated with the prognosis of several cancers, including non-metastatic renal cell carcinoma (RCC). In the present study, we evaluate the prognostic significance of SII in patients with metastatic RCC (mRCC) treated with systemic therapy. Method: Relevant studies were searched comprehensively from Web of Science, PubMed, Embase and the Cochrane Library up to January 2024. The pooled hazard ratio (HR) and 95% confidence interval (CI) were extracted from each study to evaluate the prognostic value of SII in patients with mRCC treated with tyrosine kinase inhibitor (TKI) or immune checkpoint inhibitor (ICI). Results: A total of 12 studies including 4,238 patients were included in the final analysis. High SII was significantly correlated to poor overall survival (OS, HR = 1.88; 95% CI 1.60-2.21; P < 0.001) and progression-free survival (PFS, HR = 1.66; 95% CI 1.39-1.99; P < 0.001). Stratified by therapy, high SII was also related to the poor OS (TKI: HR = 1.63, P < 0.001; ICI: HR = 2.27, P < 0.001) and PFS (TKI: HR = 1.67, P < 0.001; ICI: HR = 1.88, P = 0.002). Conclusion: In conclusion, high SII could serve as an unfavorable factor in patients with mRCC treated with systemic therapy. Stratified by therapies, the elevated SII was also associated with worse prognosis. Whereas, more prospective and large-scale studies are warranted to validate our findings. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024522831, identifier CRD42024522831.

Asparagine: A key metabolic junction in targeted tumor therapy.

Nutrient bioavailability in the tumor microenvironment plays a pivotal role in tumor proliferation and metastasis. Among these nutrients, glutamine is a key substance that promotes tumor growth and proliferation, and its downstream metabolite asparagine is also crucial in tumors. Studies have shown that when glutamine is exhausted, tumor cells can rely on asparagine to sustain their growth. Given the reliance of tumor cell proliferation on asparagine, restricting its bioavailability has emerged as promising strategy in cancer treatment. For instance, the use of asparaginase, an enzyme that depletes asparagine, has been one of the key chemotherapies for acute lymphoblastic leukemia (ALL). However, tumor cells can adapt to asparagine restriction, leading to reduced chemotherapy efficacy, and the mechanisms by which different genetically altered tumors are sensitized or adapted to asparagine restriction vary. We review the sources of asparagine and explore how limiting its bioavailability impacts the progression of specific genetically altered tumors. It is hoped that by targeting the signaling pathways involved in tumor adaptation to asparagine restriction and certain factors within these pathways, the issue of drug resistance can be addressed. Importantly, these strategies offer precise therapeutic approaches for genetically altered cancers.

Synthesis of metal-free benzimidazole-based catalysts and its application in CO2 cycloaddition.

Ionic polymers functionalized with hydroxyl, carboxyl, and amino groups can enhance the catalytic activity of catalysts. However, the straightforward preparation of bifunctional ionic polymers containing abundant ionic active sites and hydrogen bond donors remains challenging. In this study, a series of porous ionic polymers (BZIs) containing different hydrogen bond donors (-NH2, -OH, -COOH) were prepared through a simple one-pot Friedel-Crafts alkylation using benzimidazole derivatives and benzyl bromide. The structures and properties of BZIs were characterized by various techniques such as Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, solid-state nuclear magnetic resonance, and scanning electron microscopy. Among the prepared catalysts (BZI-NH2, BZI-OH, and BZI-COOH), BZI-NH2 exhibited the highest catalytic activity and recyclability, achieving a yield of 97% in the CO2 cycloaddition. The synergistic effect of Br-, hydrogen bond donors (-NH-, -NH2), and N+ in BZI-NH2 was found to contribute to its superior catalytic performance. DFT calculations were employed to study the effect of hydrogen bonds, Br-, and N+ in BZI-NH2 and BZI-OH on the CO2 cycloaddition. Using BZI-NH2 as an example, a mechanism was proposed for the synergistic effect between amino groups and bromide ions in catalyzing the CO2 cycloaddition reaction.

Association of serum interleukin-2 with severity and prognosis in hospitalized patients with community-acquired pneumonia: a prospective cohort study.

The prior studies have shown that interleukin-2 (IL-2) exerts important roles in the pathological and physiological processes of lung diseases. However, the role of IL-2 in community-acquired pneumonia (CAP) is still uncertain. Through a prospective cohort study, our research will explore the correlations between serum IL-2 levels and the severity and prognosis in CAP patients. There were 267 CAP patients included. Blood samples were obtained. Serum IL-2 were tested by enzyme-linked immunosorbent assay (ELISA). Demographic traits and clinical characteristics were extracted. Serum IL-2 were gradually elevated with increasing severity scores in CAP patients. Correlation analyses revealed that serum IL-2 were connected with physiological parameters including liver and renal function in CAP patients. According to a logistic regression analysis, serum IL-2 were positively correlated with CAP severity scores. We also tracked the prognostic outcomes of CAP patients. The increased risks of adversely prognostic outcomes, including mechanical ventilation, vasoactive agent usage, ICU admission, death, and longer hospital length, were associated with higher levels of IL-2 at admission. Serum IL-2 at admission were positively associated with severe conditions and poor prognosis among CAP patients, indicated that IL-2 may involve in the initiation and development of CAP. As a result, serum IL-2 may be an available biomarker to guide clinicians in assessing the severity and determining the prognosis of CAP.

Enhancing predictive validity of motoric cognitive risk syndrome for incident dementia and all-cause mortality with handgrip strength: insights from a prospective cohort study.

Background: This study aimed to assess whether integrating handgrip strength (HGS) into the concept of motoric cognitive risk (MCR) would enhance its predictive validity for incident dementia and all-cause mortality. Methods: A cohort of 5, 899 adults from the Health and Retirement Study underwent assessments of gait speed, subjective cognitive complaints, and HGS were involved. Over a 10-year follow-up, biennial cognitive tests and mortality data were collected. Cox proportional hazard analyses assessed the predictive power of MCR alone and MCR plus HGS for incident dementia and all-cause mortality. Results: Patients with MCR and impaired HGS (MCR-HGS) showed the highest adjusted hazard ratios (AHR) for dementia (2.33; 95% CI, 1.49-3.65) and mortality (1.52; 95% CI, 1.07-2.17). Even patients with MCR and normal HGS (MCR-non-HGS) experienced a 1.77-fold increased risk of incident dementia; however, this association was not significant when adjusted for socioeconomic status, lifestyle factors, and medical conditions. Nevertheless, all MCR groups demonstrated increased risks of all-cause mortality. The inclusion of HGS in the MCR models significantly improved predictive discrimination for both incident dementia and all-cause mortality, as indicated by improvements in the C-statistic, integrated discrimination improvement (IDI) and net reclassification indices (NRI). Conclusion: Our study underscores the incremental predictive value of adding HGS to the MCR concept for estimating risks of adverse health outcomes among older adults. A modified MCR, incorporating HGS, could serve as an effective screening tool during national health examinations for identifying individuals at risk of dementia and mortality.

Two new compounds isolated from the aerial parts of gastrodia elata blume.

Two new aromatic compounds, namely gastupdin A (1), and gastupdin B (2), together with three known compounds, arundin(3), phomosines B (4) and monocillin IV (5), were isolated from the aerial parts of Gastrodia elata Blume. The structures of the new compounds were confirmed through spectral analyses including NMR, HR-ESI-MS, ECD, UV, and IR. All isolated compounds were evaluated for their neuroprotective effects against 6-hydroxydopamine-induced cell death in Human Neuroblastoma Cells, with curcumin as the positive control, however, the activity of all compounds was weaker than the positive control, showing no significant activity.

Enhancing Wound Recovery: A Self-Gelling Powder for Improved Hemostasis and Healing.

A novel self-gelatinizing powder was designed to accelerate wound healing through enhanced hemostasis and tissue recovery. Significantly, this research addresses the critical need for innovative wound management solutions by presenting a novel approach. Carboxymethylcellulose calcium (CMC-Ca) was synthesized using an ion exchange method, and lysine (Lys) was integrated through physical mixing to augment the material's functional characteristics. The prepared powder underwent comprehensive evaluation for its self-gelling capacity, gelation time, adhesion, swelling rate, coagulation efficiency, hemostatic effectiveness, and wound healing promotion. Results indicate that the self-gelatinizing powder exhibited remarkable water absorption capabilities, absorbing liquid up to 30 times its weight and achieving rapid coagulation within 3 min. The inclusion of Lys notably enhanced the powder's gel-forming properties. The gelation time was determined to be within 4 s using a rotational rheometer, with the powder rapidly forming a stable gel on the skin surface. Furthermore, in a mouse skin injury model, near-complete skin recovery was observed within 14 days, underscoring the powder's impressive self-healing attributes and promising application prospects in wound management.

Surface Functionalization of Bamboo via Photo-Grafting Tannic Acid for Enhanced Silver Ion Loading Properties.

Photo-grafting is a gentle, simple, and precise approach to incorporating specific functional molecules for the surface functionalization of substrates. In this work, ultraviolet (UV)-induced tannic acid (TA) grafting onto the surface of bamboo was proposed as a viable strategy for functionalizing bamboo. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) clearly indicated that TA was successfully introduced to the bamboo's surface. The optimal conditions for the grafting reaction were determined to be 15 mM Methyl-2-benzoylbenzoate (BB), 30 mM TA, 20 min, and a pH = 8. Under these conditions, the amount of TA grafted onto the bamboo's surface was measured to be 19.98 µg/cm2. Results from Inductively Coupled Plasma (ICP) and Energy Dispersive Spectrometer (EDS) analyses showed that the silver ion loading capacity of tannic acid-grafted bamboo was significantly improved compared to that of raw bamboo and tannic acid-impregnated bamboo. Furthermore, the presence of TA grafted on the bamboo's surface exhibited a positive correlation with the loading of silver ions, indicating that grafted TA plays an important role in the surface functionalization of bamboo. We believe that photo-grafted TA may help generate multifunctional bamboo with diverse properties.

Genetic Engineering for Enhancing Sugarcane Tolerance to Biotic and Abiotic Stresses.

Sugarcane, a vital cash crop, contributes significantly to the world's sugar supply and raw materials for biofuel production, playing a significant role in the global sugar industry. However, sustainable productivity is severely hampered by biotic and abiotic stressors. Genetic engineering has been used to transfer useful genes into sugarcane plants to improve desirable traits and has emerged as a basic and applied research method to maintain growth and productivity under different adverse environmental conditions. However, the use of transgenic approaches remains contentious and requires rigorous experimental methods to address biosafety challenges. Clustered regularly interspaced short palindromic repeat (CRISPR) mediated genome editing technology is growing rapidly and may revolutionize sugarcane production. This review aims to explore innovative genetic engineering techniques and their successful application in developing sugarcane cultivars with enhanced resistance to biotic and abiotic stresses to produce superior sugarcane cultivars.

A lumped parameter model for evaluating coronary artery blood supply capacity.

The coronary artery constitutes a vital vascular system that sustains cardiac function, with its primary role being the conveyance of indispensable nutrients to the myocardial tissue. When coronary artery disease occurs, it will affect the blood supply of the heart and induce myocardial ischemia. Therefore, it is of great significance to numerically simulate the coronary artery and evaluate its blood supply capacity. In this article, the coronary artery lumped parameter model was derived based on the relationship between circuit system parameters and cardiovascular system parameters, and the blood supply capacity of the coronary artery in healthy and stenosis states was studied. The aortic root pressure calculated by the aortic valve fluid-structure interaction (AV FSI) simulator was employed as the inlet boundary condition. To emulate the physiological phenomenon of sudden pressure drops resulting from an abrupt reduction in blood vessel radius, a head loss model was connected at the coronary artery's entrance. For each coronary artery outlet, the symmetric structured tree model was appended to simulate the terminal impedance of the missing downstream coronary arteries. The particle swarm optimization (PSO) algorithm was used to optimize the blood flow viscous resistance, blood flow inertia, and vascular compliance of the coronary artery model. In the stenosis states, the relative flow and fractional flow reserve (FFR) calculated by numerical simulation corresponded to the published literature data. It was anticipated that the proposed model can be readily adapted for clinical application, serving as a valuable reference for diagnosing and treating patients.

Emergence of Erythromycin-Resistant and Pertactin- and Filamentous Hemagglutinin-Deficient Bordetella pertussis Strains - Beijing, China, 2022-2023.

What is already known about this topic?: Pertussis has reemerged as a significant public health threat, primarily due to variations in Bordetella pertussis strains, antimicrobial resistance, and vaccine evasion. What is added by this report?: All isolated strains were identified as ptxA1/ptxC2/ptxP3/prn150/fim2-1/fim3-1/fhaB1/tcfA2 type and exhibited resistance to erythromycin. Two strains showed a deficiency in Fha, thirty in Prn, and one strain exhibited multiple immunogen deficiencies. What are the implications for public health practice?: The emergence and spread of immunogen-deficient strains likely result from prolonged vaccine selection pressure, posing challenges to the efficacy of pertussis vaccines. Additionally, the ongoing dissemination of ptxP3 strains with high-level macrolide resistance presents a significant obstacle to clinical treatment strategies.

Does environmental pollution reduce residents' income? Evidence from CFPS in China.

Understanding the relationship between environmental pollution and residents' income is extremely important for promoting sustained progress and high-quality economic growth. This research examines the impact, mechanism, and heterogeneity of environmental contamination on residents' earnings by fusing the micro data from China Family Panel Survey with the macro data of government statistics. The results reveal that environmental degradation has a significantly negative impact on residents' individual income. Further research on the intermediary mechanism finds that environmental pollution plays a harmful role in residents' income by reducing residents' subjective well-being and labor employment. Besides, the income effect of environmental pollution is significantly heterogeneous among different regions and differentiated groups. The deteriorating environmental quality widens urban-rural income gap and increases wage inequality of inhabitants in eastern, central, and western regions of China. The gender income gap and the income disparity between different income brackets also expand with environmental deterioration. These findings not only prove that long-term development at the cost of the ecological environment is undesirable, but also demonstrate the important role of the improvement of ecological environmental quality in promoting human well-being.

Lanternarene-Based Self-Sorting Double-Network Hydrogels for Flexible Strain Sensors.

Conductive flexible hydrogels have attracted immense attentions recently due to their wide applications in wearable sensors. However, the poor mechanical properties of most conductive polymer limit their utilizations. Herein, a double network hydrogel is fabricated via a self-sorting process with cationic polyacrylamide as the first flexible network and the lantern[33]arene-based hydrogen organic framework nanofibers as the second rigid network. This hydrogel is endowed with good conductivity (0.25 S m-1) and mechanical properties, such as large Young's modulus (31.9 MPa), fracture elongation (487%) and toughness (6.97 MJ m-3). The stretchability of this hydrogel is greatly improved after the kirigami cutting, which makes it can be used as flexible strain sensor for monitoring human motions, such as bending of fingers, wrist and elbows. This study not only provides a valuable strategy for the construction of double network hydrogels by lanternarene, but also expands the application of the macrocycle hydrogels to flexible electronics.

Preparation of multi-functional active packaging film of Galla chinensis waste CDs/pullulan.

In this study, multifunctional green carbon dots (CDs) have been synthesized using Galla chinensis waste (GCW) via hydrothermal method for the first time. An active packaging film has been developed in this work by combining CDs and pullulan (PL), using the solution-casting method. The microscopic morphology revealed that the CDs that were prepared using GCW exhibited good compatibility with PL. In addition, it also led to improvement in the toughness of the PL film (14.01 % to 20.26 %), along with its water vapor permeability value [1.31 to 0.53 (g·mm)/(kPa·h·m2)]. The composite films consisting of CDs exhibited good UV blocking rates for the UVA (90.41 %-7.87 %), UVB (87.76 %-0.08 %), and UVC (83.39 %-0 %) spectral ranges. The composite films exhibited strong antioxidant activity, and the clearance of ABTS and DPPH were obtained to be 93.61 % and 86.30 %, respectively. In addition, the composite films showed good antibacterial activity for E. coli and S. aureus, with a high antibacterial rate of up to 99.99 %. Finally, the non-contact preservation of strawberries over a duration of 10 d at room temperature confirmed that the prepared composite film can help preserve the quality of strawberries, as well as extended their shelf-life.

An insect lac blanket-mimetic and degradable shellac hydrogel/chitosan packaging film with controllable gas permeation for fresh-cut vegetables preservation.

Fresh-cut products are extremely perishable due to the processing operations, and the atmosphere environment, especially CO2, O2 and H2O, could profoundly affect their shelf life. Herein, an insect "lac blanket"-mimetic and facile strategy was proposed for fresh-cut vegetables preservation, employing porous shellac hydrogel microparticles as gas "switches" in chitosan film to regulate CO2, O2 and H2O vapor permeability. Thus, the shellac hydrogel/chitosan hybrid film presented the controllable and wide range of gas permeability, compared with the chitosan film. The shellac-COOH nanoscale vesicles aggregated to form shellac hydrogel network via hydrophobic binding. The shellac hydrogel microparticles played a certain lubricating effect on the hybrid film casting solution. The hydrogen bond network between shellac hydrogel and chitosan contributed to the excellent mechanical properties of the hybrid film. The hybrid film also exhibited remarkable water-resistant, antifogging properties, optical transparency and degradability. The hybrid packaging films prepared through this strategy could adjust the internal gas (CO2, O2, H2O and ethylene) contents within the packages, and further exhibited admirable preservation performance on three fresh-cut vegetables with different respiratory metabolisms. This gas permeation-controlled strategy has great potential in fresh food preservation and various other applications that need a modified atmosphere.

Four novel Cit7GlcTs functional in flavonoid 7-O-glucoside biosynthesis are vital to flavonoid biosynthesis shunting in citrus.

Citrus fruits have abundant flavonoid glycosides (FGs), an important class of natural functional and flavor components. However, there have been few reports about the modification of UDP-glycosyltransferases (UGTs) on flavonoids in citrus. Notably, in flavonoid biosynthesis, 7-O-glucosylation is the initial and essential step of glycosylation prior to the synthesis of flavanone disaccharides, the most abundant and iconic FGs in citrus fruits. Here, based on the accumulation of FGs observed at the very early fruit development stage of two pummelo varieties, we screened six novel flavonoid 7-O-glucosyltransferase genes (7GlcTs) via transcriptomic analysis and then characterized them in vitro. The results revealed that four Cg7GlcTs possess wide catalytic activities towards various flavonoid substrates, with CgUGT89AK1 exhibiting the highest catalytic efficiency. Transient overexpression of CgUGT90A31 and CgUGT89AK1 led to increases in FG synthesis in pummelo leaves. Interestingly, these two genes had conserved sequences and consistent functions across different germplasms. Moreover, CitUGT89AK1 was found to play a role in the response of citrus to Huanglongbing infection by promoting FG production. The findings improve our understanding of flavonoid 7-O-glucosylation by identifying the key genes, and may help improve the benefits of flavonoid biosynthesis for plants and humans in the future.

CanCellVar: A database for single-cell variants map in human cancer.

Numerous variants, including both single-nucleotide variants (SNVs) in DNA and A>G RNA edits in mRNA as essential drivers of cellular proliferation and tumorigenesis, are commonly associated with cancer progression and growth. Thus, mining and summarizing single-cell variants will provide a refined and higher-resolution view of cancer and further contribute to precision medicine. Here, we established a database, CanCellVar, which aims to provide and visualize the comprehensive atlas of single-cell variants in tumor microenvironment. The current CanCellVar identified ∼3 million variants (∼1.4 million SNVs and ∼1.4 million A>G RNA edits) involved in 2,754,531 cells of 5 major cell types across 37 cancer types. CanCellVar provides the basic annotation information as well as cellular and molecular function properties of variants. In addition, the clinical relevance of variants can be obtained including tumor grade, treatment, metastasis, and others. Several flexible tools were also developed to aid retrieval and to analyze cell-cell interactions, gene expression, cell-development trajectories, regulation, and molecular structure affected by variants. Collectively, CanCellVar will serve as a valuable resource for investigating the functions and characteristics of single-cell variations and their roles in human tumor evolution and treatment.

Challenging of ECMO application in pediatric restrictive cardiomyopathy: case report of a novel TNNI3 variant.

Background: Restrictive cardiomyopathy (RCM) represents a rare cardiovascular disorder stemming from filament-associated genes. Nonetheless, treating RCM presents considerable challenges, particularly concerning device implantation and mechanical support. Furthermore, elucidating the molecular function of specific variants holds promise in benefiting patients and enhancing prognosis, given the significant heterogeneity among RCM variants. Case presentation: The proband, an eight-year-old female, was admitted to our hospital post cardiopulmonary resuscitation due to sudden cardiac arrest. Echocardiography revealed bilateral atrial enlargement. Whole-exome sequencing uncovered a novel heterozygous mutation (c.509G>A, p.R170Q) in TNNI3. Evaluation using the MutationTaster application deemed c.509G>A pathogenic (probability = 0.99). Following clinical manifestations, imaging assessments, and genetic screening, the proband received an RCM diagnosis. ECMO was recommended along with continuous renal replacement therapy. However, persistent atrial flutter ensued post-ECMO withdrawal. Attempts to restore cardiac rhythm with cardioversion, metoprolol, and amiodarone proved futile. Subsequent heart failure led to the patient's demise due to cardiac shock. Based on crystal protein structural analysis, we observed that cTnI-R170Q and R170W exerted similar impacts on protein structural stability and formation. However, both differed significantly from cTnI-R170G, primarily influencing amino acid regions 32-79 and 129-149, involved in TnC and actin binding. Therefore, cTnI-R170Q was revealed to induce RCM via the same molecular mechanism as cTnI-R170W. Conclusion: Managing RCM remains a critical challenge. This study underscores the discouragement of device implantations for cardiac pump functional support in RCM, particularly for non-short-term scheduled HTx. Additionally, considering catheter ablation for atrial fibrosis-induced AFs is recommended. Mechanistically, cTnI-R170Q primarily diminishes troponin-actin interactions and destabilizes thin filaments.