Argonaute-2 autoantibodies: a promising biomarker for predicting mortality in HBV-related acute-on-chronic liver failure patients with cirrhosis.

Background & aims: HBV infection initiates autoimmune responses, leading to autoantibody generation. This research explores the role of autoantibodies in HBV-related Acute-on-Chronic Liver Failure (ACLF), offering novel perspectives for clinical management. Method: We applied immunoprecipitation and iTRAQ techniques to screen for autoantibodies in serum from HBV-related cirrhosis patients and conducted detection with conformation- stabilizing ELISA in a cohort of 238 HBV-infected individuals and 49 health controls. Our results were validated in a retrospective cohort comprising 106 ACLF patients and further assessed through immunohistochemical analysis in liver tissues from an additional 10 ACLF cases. Results: Utilizing iTRAQ, we identified Argonaute1-3 autoantibodies (AGO-Abs) in this research. AGO2-Abs notably increased in cirrhosis, decompensation, and further in ACLF, unlike AGO1-Abs and AGO3-Abs. This reflects disease severity correlation. Logistic regression and COX models confirmed AGO2-Abs as independent prognostic indicators for decompensated liver cirrhosis (DLC) and ACLF. In the ROC analysis, AGO2-Abs showed significant diagnostic value for predicting 28- and 90-day mortality (AUROC = 0.853 and 0.854, respectively). Furthermore, combining AGO2-Abs with the Child-Pugh, MELD, and AARC scores significantly improved their predictive accuracy (P < 0.05). Kaplan-Meier analysis showed poorer survival for AGO2-Abs levels above 99.14µg/ml. These findings were supported by a retrospective validation cohort. Additionally, immunohistochemistry revealed band-like AGO2 expression in periportal liver areas, with AGO2-Abs levels correlating with total bilirubin, indicating a potential role in exacerbating liver damage through periportal functions. Conclusions: AGO2-Abs is a robust biomarker for predicting the mortality of patients with HBV-related ACLF.

Polyphenols targeting multiple molecular targets and pathways for the treatment of vitiligo.

Vitiligo, a pigmentary autoimmune disorder, is marked by the selective loss of melanocytes in the skin, leading to the appearance of depigmented patches. The principal pathological mechanism is the melanocyte destruction mediated by CD8+ T cells, modulated by oxidative stress and immune dysregulation. Vitiligo affects both physical health and psychological well-being, diminishing the quality of life. Polyphenols, naturally occurring compounds with diverse pharmacological properties, including antioxidant and anti-inflammatory activities, have demonstrated efficacy in managing various dermatological conditions through multiple pathways. This review provides a comprehensive analysis of vitiligo and the therapeutic potential of natural polyphenolic compounds. We examine the roles of various polyphenols in vitiligo management through antioxidant and immunomodulatory effects, melanogenesis promotion, and apoptosis reduction. The review underscores the need for further investigation into the precise molecular mechanisms of these compounds in vitiligo treatment and the exploration of their combination with current therapies to augment therapeutic outcomes.

MXenes for Wearable Physical Sensors toward Smart Healthcare.

The gradual rise of personal healthcare awareness is accelerating the deployment of wearable sensors, whose ability of acquiring physiological vital signs depends on sensing materials. MXenes have distinct chemical and physical superiorities over other 2D nanomaterials for wearable sensors. This review presents a comprehensive summary of the latest advancements in MXenes-based materials for wearable physical sensors. It begins with an introduction to special structural features of MXenes for sensing performance, followed by an in-depth exploration of versatile functionalities. A detailed description of different sensing mechanisms is also included to illustrate the contribution of MXenes to the sensing performance and its improvement. In addition, the real-world applications of MXenes-based physical sensors for monitoring different physiological signs are included as well. The remaining challenges of MXenes-based materials for wearable physical sensors and their promising opportunities are finally narrated, in conjunction with a prospective for future development.

A rare missense p.C125Y mutation in the TNFRSF1A gene identified in a Chinese family with tumor necrosis factor receptor-associated periodic fever syndrome.

Background: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a rare autosomal dominant disorder with a low incidence in Asia. The most frequent clinical manifestations include fever, rash, myalgia, joint pain and abdominal pain. Misdiagnosis rates are high because of the clinical and genetic variability of the disease. The pathogenesis of TRAPS is complex and yet to be fully defined. Early genetic diagnosis is the key to precise treatment. Methods: In this study, a Chinese family with suspected TRAPS were analyzed by genome-wide SNP genotyping, linkage analysis and targeted sequencing for identification of mutations in causative genes. To study the pathogenicity of the identified gene mutation, we performed a conservation analysis of the mutation site and protein structure analysis. Flow cytometry was used to detect TNFRSF1A shedding and quantitative real-time PCR were used to assess the activation of unfolded protein response (UPR) in the mutation carriers and healthy individuals. Results: A typical TRAPS family history, with a pattern of autosomal dominant inheritance, led to the identification of a rare mutation in the TNFRSF1A gene (c.G374A [p.Cys125Tyr]) with unknown significance. The patient responded well to corticosteroids, and long-term therapy with colchicine effectively reduced the inflammatory attacks. No amyloid complications occurred during the 6-year follow-up. In silico protein analysis showed that the mutation site is highly conversed and the mutation prevents the formation of intrachain disulfide bonds in the protein. Despite a normal shedding of the TNFRSF1A protein from stimulated monocytes in the TRAPS patients with p.C125Y mutation, the expression of CHOP and the splicing of XBP1 was significantly higher than healthy controls, suggesting the presence of an activation UPR. Conclusion: This is the first report of a Chinese family with the rare p.C125Y mutation in TNFRSF1A. The p.C125Y mutation does not result in aberrant receptor shedding, but instead is associated with an activated UPR in these TRAPS patients, which may provide new insights into the pathogenesis of this rare mutation in TRAPS.

Cytotoxic and viricidal effects of human semen on mumps virus-infected lymphocytes: In vitro studies.

Viruses in human semen may be sexually transmitted via free and cell-mediated viral infection. The potential effects of semen on the infection and sexual transmission of most viruses in semen remain largely unclear. The present study elucidated the inhibitory effects of human seminal plasma (SP) on Jurkat cell (JC)-mediated mumps virus (MuV) infection. We demonstrated that MuV efficiently infected JCs and that the JCs infected by MuV (JC-MuV) mediated MuV infection of HeLa cells. Remarkably, SP was highly cytotoxic to JCs and inhibited JC-MuV infection of HeLa cells. The cytotoxic factor possessed a molecular weight of less than 3 kDa, whereas that of the viricidal factor was over 100 kDa. The cooperation of cytotoxic and viricidal factors was required for the SP inhibition of JC-MuV infection, and prostatic fluid (PF) was responsible for both the cytotoxic and viricidal effects of SP. The cytotoxic effects we observed were resistant to the treatment of PF with boiling water, proteinase K, RNase A, and DNase I. Our results provide novel insights into the antiviral properties of SP, which may limit cell-mediated sexual viral transmission.

Research Progress on the Pathogenesis, Diagnosis, and Drug Therapy of Alzheimer's Disease.

As the population ages worldwide, Alzheimer's disease (AD), the most prevalent kind of neurodegenerative disorder among older people, has become a significant factor affecting quality of life, public health, and economies. However, the exact pathogenesis of Alzheimer's remains elusive, and existing highly recognized pathogenesis includes the amyloid cascade hypothesis, Tau neurofibrillary tangles hypothesis, and neuroinflammation hypothesis. The major diagnoses of Alzheimer's disease include neuroimaging positron emission computed tomography, magnetic resonance imaging, and cerebrospinal fluid molecular diagnosis. The therapy of Alzheimer's disease primarily relies on drugs, and the approved drugs on the market include acetylcholinesterase drugs, glutamate receptor antagonists, and amyloid-ß monoclonal antibodies. Still, the existing drugs can only alleviate the symptoms of the disease and cannot completely reverse it. This review aims to summarize existing research results on Alzheimer's disease pathogenesis, diagnosis, and drug therapy, with the objective of facilitating future research in this area.

Glycosylation editing: an innovative therapeutic opportunity in precision oncology.

Cancer is still one of the most arduous challenges in the human society, even though humans have found many ways to try to conquer it. With our incremental understandings on the impact of sugar on human health, the clinical relevance of glycosylation has attracted our attention. The fact that altered glycosylation profiles reflect and define different health statuses provide novel opportunities for cancer diagnosis and therapeutics. By reviewing the mechanisms and critical enzymes involved in protein, lipid and glycosylation, as well as current use of glycosylation for cancer diagnosis and therapeutics, we identify the pivotal connection between glycosylation and cellular redox status and, correspondingly, propose the use of redox modulatory tools such as cold atmospheric plasma (CAP) in cancer control via glycosylation editing. This paper interrogates the clinical relevance of glycosylation on cancer and has the promise to provide new ideas for laboratory practice of cold atmospheric plasma (CAP) and precision oncology therapy.

A Novel Homozygous RHOH Variant Associated with T Cell Dysfunction and Recurrent Opportunistic Infections.

RHOH, an atypical small GTPase predominantly expressed in hematopoietic cells, plays a vital role in immune function. A deficiency in RHOH has been linked to epidermodysplasia verruciformis, lung disease, Burkitt lymphoma and T cell defects. Here, we report a novel germline homozygous RHOH c.245G > A (p.Cys82Tyr) variant in a 21-year-old male suffering from recurrent, invasive, opportunistic infections affecting the lungs, eyes, and brain. His sister also succumbed to a lung infection during early adulthood. The patient exhibited a persistent decrease in CD4+ T, B, and NK cell counts, and hypoimmunoglobulinemia. The patient's T cell showed impaired activation upon in vitro TCR stimulation. In Jurkat T cells transduced with RHOHC82Y, a similar reduction in activation marker CD69 up-regulation was observed. Furthermore, the C82Y variant showed reduced RHOH protein expression and impaired interaction with the TCR signaling molecule ZAP70. Together, these data suggest that the newly identified autosomal-recessive RHOH variant is associated with T cell dysfunction and recurrent opportunistic infections, functioning as a hypomorph by disrupting ZAP70-mediated TCR signaling.

Genome-wide identification and analysis of the cotton ALDH gene family.

BACKGROUND: Aldehyde dehydrogenases (ALDHs) are a family of enzymes that catalyze the oxidation of aldehyde molecules into the corresponding carboxylic acid, regulate the balance of aldehydes and protect plants from the poisoning caused by excessive accumulation of aldehydes; however, this gene family has rarely been studied in cotton. RESULTS: In the present study, genome-wide identification was performed, and a total of 114 ALDH family members were found in three cotton species, Gossypium hirsutum, Gossypium arboreum and Gossypium raimondii. The ALDH genes were divided into six subgroups by evolutionary analysis. ALDH genes in the same subgroup showed similar gene structures and conserved motifs, but some genes showed significant differences, which may result in functional differences. Chromosomal location analysis and selective pressure analysis revealed that the ALDH gene family had experienced many fragment duplication events. Cis-acting element analysis revealed that this gene family may be involved in the response to various biotic and abiotic stresses. The RT‒qPCR results showed that the expression levels of some members of this gene family were significantly increased under salt stress conditions. Gohir.A11G040800 and Gohir.D06G046200 were subjected to virus-induced gene silencing (VIGS) experiments, and the sensitivity of the silenced plants to salt stress was significantly greater than that of the negative control plants, suggesting that Gohir.A11G040800 and Gohir.D06G046200 may be involved in the response of cotton to salt stress. CONCLUSIONS: In total, 114 ALDH genes were identified in three Gossypium species by a series of bioinformatics analysis. Gene silencing of the ALDH genes of G. hirsutum revealed that ALDH plays an important role in the response of cotton to salt stress.

Mechanical Properties of a Honeycomb Structure Dispersed with 3D-Printed Fe3O4 Nanomaterials.

The honeycomb structure demonstrates exceptional stability, efficient mechanical performance, outstanding load-bearing capacity, and energy-saving and lightweight properties, rendering it extensively employed in various fields such as industrial manufacturing, radiation protection building, aerospace engineering, and wave-absorbing stealth materials. Bionic design can enhance the performance of structures, making bionic honeycomb design valuable in engineering. This study employs a bionic optimization design based on the original honeycomb size to investigate the impact of a new composite honeycomb core structure on mechanical properties. Orthogonal experiments are conducted to explore the effect of honeycomb size on mechanical properties and determine the optimal size. Combining numerical simulation and 3D printing experiments, we examine the mechanical properties of both nano-Fe3O4 particle-distributed honeycomb structure and common structures, analyzing mechanisms behind their tensile and compressive properties.

Current status of controlled onco-therapies based on metal organic frameworks.

Despite consecutive efforts devoted to the establishment of innovative therapeutics for cancer control, cancer remains as a primary global public health concern. Achieving controlled release of anti-cancer agents may add great value to the field of oncology that requires the involvement of nanotechnologies. Metal organic frameworks (MOFs) hold great promise in this regard owing to their unique structural properties. MOFs can act as superior candidates for drug delivery given their porous structure and large loading area, and can be prepared into anti-cancer therapeutics by incorporating stimuli-sensitive components into the ligands or nodes of the framework. By combing through chemical and physical features of MOFs favorable for onco-therapeutic applications and current cancer treatment portfolios taking advantages of these characteristics, this review classified MOFs feasible for establishing controlled anti-cancer modalities into 6 categories, outlined the corresponding strategies currently available for each type of MOF, and identified understudied areas and future opportunities towards innovative MOF design for improved or expanded clinical anti-cancer applications.

Exploring the autophagy-related pathogenesis of active ulcerative colitis.

BACKGROUND: The pathogenesis of ulcerative colitis (UC) is complex, and recent therapeutic advances remain unable to fully alleviate the condition. AIM: To inform the development of novel UC treatments, bioinformatics was used to explore the autophagy-related pathogenesis associated with the active phase of UC. METHODS: The GEO database was searched for UC-related datasets that included healthy controls who met the screening criteria. Differential analysis was conducted to obtain differentially expressed genes (DEGs). Autophagy-related targets were collected and intersected with the DEGs to identiy differentially expressed autophagy-related genes (DEARGs) associated with active UC. DEARGs were then subjected to KEGG, GO, and DisGeNET disease enrichment analyses using R software. Differential analysis of immune infiltrating cells was performed using the CiberSort algorithm. The least absolute shrinkage and selection operator algorithm and protein-protein interaction network were used to narrow down the DEARGs, and the top five targets in the Dgree ranking were designated as core targets. RESULTS: A total of 4822 DEGs were obtained, of which 58 were classified as DEARGs. SERPINA1, BAG3, HSPA5, CASP1, and CX3CL1 were identified as core targets. GO enrichment analysis revealed that DEARGs were primarily enriched in processes related to autophagy regulation and macroautophagy. KEGG enrichment analysis showed that DEARGs were predominantly associated with NOD-like receptor signaling and other signaling pathways. Disease enrichment analysis indicated that DEARGs were significantly linked to diseases such as malignant glioma and middle cerebral artery occlusion. Immune infiltration analysis demonstrated a higher presence of immune cells like activated memory CD4 T cells and follicular helper T cells in active UC patients than in healthy controls. CONCLUSION: Autophagy is closely related to the active phase of UC and the potential targets obtained from the analysis in this study may provide new insight into the treatment of active UC patients.

Transforming free-text radiology reports into structured reports using ChatGPT: A study on thyroid ultrasonography.

PURPOSE: The importance of structured radiology reports has been fully recognized, as they facilitate efficient data extraction and promote collaboration among healthcare professionals. Our purpose is to assess the accuracy and reproducibility of ChatGPT, a large language model, in generating structured thyroid ultrasound reports. METHODS: This is a retrospective study that includes 184 nodules in 136 thyroid ultrasound reports from 136 patients. ChatGPT-3.5 and ChatGPT-4.0 were used to structure the reports based on ACR-TIRADS guidelines. Two radiologists evaluated the responses for quality, nodule categorization accuracy, and management recommendations. Each text was submitted twice to assess the consistency of the nodule classification and management recommendations. RESULTS: On 136 ultrasound reports from 136 patients (mean age, 52 years ± 12 [SD]; 61 male), ChatGPT-3.5 generated 202 satisfactory structured reports, while ChatGPT-4.0 only produced 69 satisfactory structured reports (74.3 % vs. 25.4 %, odds ratio (OR) = 8.490, 95 %CI: 5.775-12.481, p < 0.001). ChatGPT-4.0 outperformed ChatGPT-3.5 in categorizing thyroid nodules, with an accuracy of 69.3 % compared to 34.5 % (OR = 4.282, 95 %CI: 3.145-5.831, p < 0.001). ChatGPT-4.0 also provided more comprehensive or correct management recommendations than ChatGPT-3.5 (OR = 1.791, 95 %CI: 1.297-2.473, p < 0.001). Finally, ChatGPT-4.0 exhibits higher consistency in categorizing nodules compared to ChatGPT-3.5 (ICC = 0.732 vs. ICC = 0.429), and both exhibited moderate consistency in management recommendations (ICC = 0.549 vs ICC = 0.575). CONCLUSIONS: Our study demonstrates the potential of ChatGPT in transforming free-text thyroid ultrasound reports into structured formats. ChatGPT-3.5 excels in generating structured reports, while ChatGPT-4.0 shows superior accuracy in nodule categorization and management recommendations.

Clinical decision support system based on deep learning for evaluating implantable collamer lens size and vault after implantable collamer lens surgery: a retrospective study.

OBJECTIVES: To aid doctors in selecting the optimal preoperative implantable collamer lens (ICL) size and to enhance the safety and surgical outcomes of ICL procedures, a clinical decision support system (CDSS) is proposed in our study. DESIGN: A retrospective study of patients after ICL surgery. SETTING: China Tertiary Myopia Prevention and Control Center. PARTICIPANTS: 2772 eyes belonging to 1512 patients after ICL surgery. Data were collected between 2018 and 2022. OUTCOME MEASURES: A CDSS is constructed and used to predict vault at 1 month postoperatively and preoperative ICL dimensions using various artificial intelligence methods. Accuracy metrics as well as area under curve (AUC) parameters are used to determine the CDSS prediction methods. RESULTS: Among the ICL size prediction models, conventional neural networks (CNNs) achieve the best prediction accuracy at 91.37% and exhibit the highest AUC of 0.842. Regarding the prediction model for vault values 1 month after surgery, CNN surpasses the other methods with an accuracy of 85.27%, which has the uppermost AUC of 0.815. Thus, we select CNN as the prediction algorithm for the CDSS. CONCLUSIONS: This study introduces a CDSS to assist doctors in selecting the optimal ICL size for patients while improving the safety and postoperative outcomes of ICL surgery.

Preparation of cellulose-based flexible SERS and its application for rapid and ultra-sensitive detection of thiram on fruits and vegetables.

In response to the prevalent issue of thiram as a common pesticide residue on the surface of fruits and vegetables, our research team employed an acidic hydrated metal salt low co-fusion solvent to dissolve cellulose lysis slurry. Subsequently, a regenerated cellulose membrane (RCM) was successfully prepared via sol-gel method. Uniformly sized Ag nanoparticles (NPs) were deposited on RCM utilizing the continuous ion layer adsorption and reaction (SILAR) technique. The resulting Ag NPs/RCM flexible surface-enhanced Raman spectroscopy (SERS) substrates exhibited a minimum detection limit of 5 × 10-9 M for Rhodamine 6G (R6G), demonstrating good uniformity (RSD = 4.86 %) and reproducibility (RSD = 3.07 %). Moreover, the substrate displayed a remarkable sensitivity of 10-10 M toward thiram standard solution. Given its inherent flexibility, the substrate proves advantageous for the detection of three-dimensional environments such as fruit and vegetable surfaces, and its practicality has been confirmed in the detection of thiram residue on apples, tomatoes, pears, and other fruits and vegetables.

Oxidation of Methanesulfinate by Hexachloroiridate(IV) and the Standard Electrode Potential of the Aqueous Methanesulfonyl Radical.

The aqueous reaction of [IrCl6]2- with CH3SO2- is biphasic and yields a 1:1 mixture of [IrCl6]3- and [IrCl5(H2O)]2- and CH3SO2Cl in the initial rapid phase. The next slow phase corresponds to the hydrolysis of CH3SO2Cl to yield CH3SO3- and Cl-. The initial phase shows kinetic inhibition by [IrCl6]3- that can be minimized by the addition of the radical scavenger propiolic acid. A detailed analysis of the kinetics indicates a mechanism with reversible outer-sphere electron transfer from CH3SO2- to [IrCl6]2- as the first step, followed by the irreversible inner-sphere oxidation of CH3SO2• by [IrCl6]2- to yield [IrCl5(H2O)]2- and CH3SO2Cl. Analysis of the inhibition by [IrCl6]3- and the kinetic effects of propiolic acid enable the determination of the equilibrium constant for the first electron-transfer step. This equilibrium constant then yields E° (CH3SO2•/CH3SO2-) = 1.01 V vs NHE at 25 °C. This is the first report of a standard potential for an alkanesulfonyl radical.

Evaluation of net carbon sequestration and ecological benefits from single biochar-incorporated sorghum farmland systems in saline-alkali areas of Inner Mongolia, China.

Biochar is widely recognized as a soil amendment to reduce greenhouse gas emissions and enhance soil carbon storage in agroecosystems; however, the systematic focus on carbon balance and ecological benefits in cropping systems remains unclear in saline-alkali areas under water-saving irrigation. Here, a 2-yr field experiment with carbon footprint method was conducted to determine soil carbon budgets, biochar carbon efficiency performance, and the economic and ecological benefits of mulched drip-irrigated sorghum production, in an arid salinized region of Inner Mongolia, China. Corn straw-derived biochar dosages of 0 (CK), 15 (B15), 30 (B30), and 45 (B45) t hm-2 were just applied into the soil in the first crop growing season. A single application of biochar to soil significantly reduced CO2 emissions for the current and subsequent crop-growing seasons, with 13.1%, 16.7%, and 12.5% reductions for B15, B30, and B45, respectively. Compared with the non-biochar control plots, B15, B30, and B45 also increased NPP by 36.7%, 38.4%, and 27.1%, respectively. The actual effects on improving net carbon sequestration for B15, B30, and B45 in the first year were higher than those in the second year, with mean increases of 1.27, 1.47, and 1.36 times, respectively; however, the efficiencies of biochar for fixing carbon per biochar dosage input for B15 were 72.8% and 64.1% higher than those of B30 and B45, respectively. Net profits were significantly improved by 57.2-87.1% by biochar treatments. The environmental benefits of biochar carbon trading revenues for B15, B30, and B45 increased by 105.9%, 162.1%, and 109.6%, respectively. The minimum observation for carbon productivity and the maximum measurements for both the economic and ecological benefits were B15. The B15 also significantly increased sorghum yield and grain number. Results demonstrate that biochar application in the current growing season helps reduce soil carbon emissions, increases net carbon sequestration for current and subsequent sorghum agroecosystems, and enhances net profit and ecological benefits. The optimal positive synergistic effect was observed at a biochar application rate of 15 t hm-2 for reducing soil carbon emissions, increasing crop production, and improving the ecological environment.

LMNA-related muscular dystrophy involving myoblast proliferation and apoptosis through the FOXO1/GADD45A pathway.

LMNA-related muscular dystrophy is a major disease phenotype causing mortality and morbidity in laminopathies, but its pathogenesis is still unclear. To explore the molecular pathogenesis, a knock-in mouse harbouring the Lmna-W520R mutation was modelled. Morphological and motor functional analyses showed that homozygous mutant mice revealed severe muscular atrophy, profound motor dysfunction, and shortened lifespan, while heterozygotes showed a variant arrangement of muscle bundles and mildly reduced motor capacity. Mechanistically, the FOXO1/GADD45A pathway involving muscle atrophy processes was found to be altered in vitro and in vivo assays. The expression levels of FOXO1 and its downstream regulatory molecule GADD45A significantly increased in atrophic muscle tissue. The elevated expression of FOXO1 was associated with decreased H3K27me3 in its gene promotor region. Overexpression of GADD45A induced apoptosis and cell cycle arrest of myoblasts in vitro, and it could be partially restored by the FOXO1 inhibitor AS1842856, which also slowed the muscle atrophy process with improved motor function and prolonged survival time of homozygous mutant mice in vivo. Notably, the inhibitor also partly rescued the apoptosis and cell cycle arrest of hiPSC-derived myoblasts harbouring the LMNA-W520R mutation. Together, these data suggest that the activation of the FOXO1/GADD45A pathway contributes to the pathogenesis of LMNA-related muscle atrophy, and it might serve as a potential therapeutic target for laminopathies.