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.

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.

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.

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.

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.

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.

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.

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.

Myoglobin improves doxycycline sensitivity in pancreatic cancer through promoting heme oxygenase-1-mediated ferroptosis.

Ferroptosis is expected to be a therapeutic target for cancers including pancreatic cancer. We aimed to screen genes that regulate ferroptosis and doxycycline resistance in pancreatic cancer and to explore the underlying mechanisms. Bioinformatics analysis was performed to identify genes that respond to ferroptosis in two human pancreatic cancer cells with GOT1 knocked down or not. 325 and 842 genes were upregulated in MiaPaCa and Tu8902 cells in response to GOT1 knockdown, with 43 genes shared. Among the 43 genes, 14 genes were identified to interact with ferroptosis key genes. MB and HMOX1 were the genes most sensitive to Erastin and doxycycline. Moreover, MB and HMOX1 expression was higher in human normal pancreatic duct epithelial cells than in pancreatic cancer cells. MB and HMOX1 proteins physically bound and promoted each other's expression. By interacting with HMOX1, MB suppressed pancreatic cancer cell proliferation, colony formation and invasion, and promoted cell ferroptosis and sensitivity to erastin and doxycycline. Silencing HMOX1 reversed the promoting effect of MB on cell ferroptosis and sensitivity to doxycycline. A pancreatic cancer xenograft model was established by subcutaneous injection of Panc-1 cells transfected with or without Ad-MB, and doxycycline was administered intraperitoneally. Overexpression of MB enhanced the inhibitory effect of doxycycline on xenograft growth. In conclusion, MB facilitated doxycycline sensitivity in pancreatic cancer cells through promoting HMOX1-mediated ferroptosis.

Ultra-sensitive detection of tumor necrosis factor alpha based on silver-coated gold core shell and magnetically separated recognition of SERS aptamer sensors.

A highly sensitive tumor necrosis factor α (TNF-α) detection method based on a surface-enhanced Raman scattering (SERS) magnetic patch sensor is reported. Magnetic beads (MNPs) and core shells were used as the capture matrix and signaling probe, respectively. For this purpose, antibodies were immobilized on the surface of magnetic beads, and then Au@4-MBN@Ag core-shell structures coupled with aptamers and TNF-α antigen were added sequentially to form a sandwich immune complex. Quantitative analysis was performed by monitoring changes in the characteristic SERS signal intensity of the Raman reporter molecule 4-MBN. The results showed that the limit of detection (LOD) of the proposed method was 4.37 × 10-15 mg·mL-1 with good linearity (R2 = 0.9918) over the concentration range 10-12 to 10-5 mg·mL-1. Excellent assay accuracy was also demonstrated, with recoveries in the range 102% to 114%. Since all reactions occur in solution and are separated by magnetic adsorption of magnetic beads, this SERS-based immunoassay technique solves the kinetic problems of limited diffusion and difficult separation on solid substrates. The method is therefore expected to be a good clinical tool for the diagnosis of the inflammatory biomarker THF-α and in vivo inflammation screening.

[Effects of Straw Biochar on Carbon Footprint of Maize Farmland Ecosystem Under Mulched Drip Irrigation in Hetao Irrigation District].

To explore the effect of biochar on greenhouse gas emissions and the carbon footprint of a corn farmland ecosystem under drip irrigation with film in an arid region, biochar treatments with different application rates[0 (CK), 15 (C15), 30 (C30), and 45 t·hm-2 (C45)] were established. The seasonal changes in soil greenhouse gases (CO2, N2O, and CH4) and their comprehensive warming potential in the maize farmland ecosystem were monitored for two consecutive years after a one-time application of biochar. The carbon emissions caused by agricultural production activities and their carbon footprint were estimated using the life cycle assessment method. Compared with that in CK, the cumulative CO2 emissions in the crop growing season decreased by 17.6%-24.7%, the cumulative N2O emissions decreased by 71.1%-110.4%, and the global warming potential decreased by 19.5%-25.9%. In the second year of the crop growing season after biochar application, the cumulative CO2 emissions were reduced by 19.2%-40.6%, the cumulative N2O emissions were reduced by 38.7-46.7%, and the comprehensive warming potential was reduced by 19.7%-40.5%. For two consecutive years, the treatment of C15 and C30 increased the cumulative absorption of CH4 to different degrees, whereas the treatment of C45 significantly decreased the cumulative absorption of CH4. C15 and C45 were the treatments with the least carbon footprint per unit yield in the current and the succeeding year of biochar application, and their carbon footprint per unit yield was 10.1% and 26.2% lower than that of CK, respectively. Soil greenhouse gas emissions showed the most contribution to the carbon footprint of the maize farmland ecosystem (38.1%-59.2%), followed by nitrogen fertilizer production (19.8%-33.4%), electric energy production (6.7%-8.8%), and plastic film mulching (4.4%-7.4%). Biochar contributed 5.7%-13.8% to the ecosystem's carbon footprint. The application of 30 t·hm-2 biochar had a better effect on carbon reduction, carbon fixation, and yield increase in the farmland ecosystem. Improving the biochar production process and transportation route, increasing nitrogen use efficiency, and developing water-saving and energy-saving irrigation technology are important ways to reduce the carbon footprint of farmland ecosystems in arid regions.

Interlocus Gene Conversion, Natural Selection, and Paralog Homogenization.

Following a duplication, the resulting paralogs tend to diverge. While mutation and natural selection can accelerate this process, they can also slow it. Here, we quantify the paralog homogenization that is caused by point mutations and interlocus gene conversion (IGC). Among 164 duplicated teleost genes, the median percentage of postduplication codon substitutions that arise from IGC rather than point mutation is estimated to be between 7% and 8%. By differentiating between the nonsynonymous codon substitutions that homogenize the protein sequences of paralogs and the nonhomogenizing nonsynonymous substitutions, we estimate the homogenizing nonsynonymous rates to be higher for 163 of the 164 teleost data sets as well as for all 14 data sets of duplicated yeast ribosomal protein-coding genes that we consider. For all 14 yeast data sets, the estimated homogenizing nonsynonymous rates exceed the synonymous rates.