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Objective: To evaluate the antitumor effects of diisopropylamine dichloroacetate (DADA) alone or in combination with chemotherapy/radiotherapy/immunotherapy in NSCLC and explore the underlying mechanisms involved. Methods: MTT, UV spectrophotometry, flow cytometry, fluorescence microscopy, and clonogenic survival assays were used. In LLC mouse models, the antitumor effects of radiotherapy, DADA, and the anti-PD-1 antibody alone or in combination were evaluated, and the T cell numbers were evaluated in different groups. Results: DADA significantly inhibited lactate production and promoted apoptosis in NSCLC in vitro. Compared with pemetrexed or DADA alone, the combination of DADA with pemetrexed significantly inhibited proliferation and promoted apoptosis (p<0.05). This may be related to the decrease in the mitochondrial membrane potential in the combined group. Moreover, compared with radiotherapy alone, the combination of DADA with radiotherapy induced remarkable DNA damage. In vivo, the combination of radiotherapy, an anti-PD-1 antibody and DADA resulted in superior tumor inhibition than the combination of radiotherapy and anti-PD-1 antibody did (p < 0.05). The underlying mechanism may be partially related to the increased number of CD3+ T cells in the triplet combination group (p < 0.05). Discussion: Our results showed that DADA has strong antitumor effects on NSCLC, either alone or in combination with chemotherapy or radiotherapy. Interestingly, the combination of radiotherapy, anti-PD-1 antibody and DADA had a more pronounced tumor-suppressing effect, which may be related to DADA-induced T-cell generation by reducing local lactic acid production in the tumor microenvironment. This study lays the foundation for further exploration of DADA in lung cancer, especially in the era of immunotherapy, on the basis of its possible immunomodulatory effects.

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High coastal nutrient loading can cause changes in seagrass chemistry traits that may lead to variability in seagrass litter decomposition processes. Such changes in decomposition have the potential to alter the carbon (C) sequestration capacity within seagrass meadows ('blue carbon'). However, the external and internal factors that drive the variability in decomposition rates of the different organic matter (OM) types of seagrass are poorly understood, especially recalcitrant OM (i.e. cellulose-associated OM and lignin-associated OM), thereby limiting our ability to evaluate the C sequestration potential. It was conducted a laboratory incubation to compare differences in the decomposition of Halophila beccarii litter collected from seagrass meadows with contrasting nutrient loading histories. The exponential decay constants of seagrass litter mass, cellulose-associated OM and lignin-associated OM were 0.009-0.032, 0.014-0.054 and 0.009-0.033 d-1, respectively. The seagrass litter collected from meadows with high nutrient loading exhibited greater losses of mass (25.0-41.2 %), cellulose-associated OM (2.8-18.5 %) and lignin-associated OM (9.6-31.2 %) than litter from relatively low nutrient loading meadows. The initial and temporal changes of the litter nitrogen (N) and phosphorus (P) concentrations, stoichiometric ratios of lignin/N, C/N, and C/P, and cellulose-associated OM content, were strongly correlated with the losses of litter mass and different types of OM. Further, temporal changes of litter C and OM types, particularly the OM and labile OM concentrations, were identified as the main driving factors for the loss of litter mass and loss of different OM types. These results indicated that nutrient-loaded seagrass litter, characterized by elevated nutrient levels and diminished amounts of recalcitrant OM, exhibits an accelerated decay rate for the recalcitrant OM. These differences in litter quality would lead to a reduced contribution of seagrass litter to long-term C stocks in eutrophic meadows, thereby weakening the stability of C sequestration. Considering the expected changes in seagrass litter chemistry traits and decay rates due to long-term nutrient loading, this study provides useful information for improving C sequestration capabilities through effective pollution management.

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Oils spilled into the ocean can form various weathered oils (non-emulsified oil slicks (NEOS), oil emulsions (OE)) which threaten the oceanic and coastal environments and ecosystems. Optical remote sensing has the unique ability to discriminate oil types and quantify oil volumes as their spectral contrasts with oil-free seawater. Here, a deep learning-based model is developed for identification, classification, and quantification of various oil types. Based on the oil-contained datasets collected from 7 satellite sensors from April 2019 to August 2023, the origin, quantity, and spatial distribution of oils spilled from ships and rigs in the China Seas are mapped in detail. We found that oil spill incidents are primarily from ship discharges (85.8 %), while platform leaks lead to more oil emulsions (58.6 % compared to 13.1 % from ships), which illuminates that the drilling oils are the main source of oil spill pollution in China Seas. The spilled oils correlate with major port locations, including offshore Qingdao and Rongcheng, Bohai Bay, the adjacent areas of Beihai, and Hue and Danang in Vietnam. This study provides new insights into the assessment and management of offshore and marine oil spills.

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S-metolachlor is a selective pre-emergence herbicide used in dryland. However, it is challenging to employ in paddy fields due to its phytotoxic effects on rice. As a common phytohormone, Gibberellin-3 (GA3) is inferred to have the ability to alleviate herbicide phytotoxicity. This study first quantitatively verified the phytotoxicity of s-metolachlor to rice and then demonstrated the mitigative effect of GA3 on these adverse reactions. Furthermore, a transcriptome of rice seedlings subjected to different treatments was constructed to assemble the reference genes, followed by comparative metabolomics and proteomics analyses. Metabolomics revealed an enrichment of flavonoid metabolites in the group of adding GA3, and these flavonoids can eliminate ROS in plants. Proteomics analysis indicated that differential proteins were enriched in the phenylpropanoid biosynthesis pathway responsible for the synthesis of flavonoids and that the functions of most differential proteins are associated with peroxidase. The proteome, combined with the transcriptome, revealed that the expressions of proteins and genes was related to the POD activity in the group of adding GA3. It was speculated that the elimination of ROS is key to alleviating the stress of s-metolachlor on rice growth. It was inferred that the mechanism of GA3 in alleviating the phytotoxicity of the substance s-metolachlor is by increasing the activity of the POD and influencing the growth of rice seedlings through the restoration of flavonoid synthesis. In this study, we screened GA3 as a safener to alleviate the phytotoxicity of s-metolachlor on rice. On this basis, the mechanism of alleviating phytotoxicity was studied. The application range of s-metolachlor might be expanded, providing a new supplementary method for weed control and herbicide resistance management.

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In this paper, a biomimetic skin microtissue biosensor was developed based on three-dimensional (3D) bioprinting to precisely and accurately determine fish parvalbumin (FV). Based on the principle that allergens stimulate cells to produce ONOO- (peroxynitrite anion), a screen-printed electrode for the detection nanomolar level ONOO- was innovatively prepared to indirectly detect FV based on the level of ONOO- release. Gelatin methacryloyl (GelMA), RBL-2H3 cells, and MS1 cells were used as bio-ink for 3D bioprinting. The high-throughput and standardized preparation of skin microtissue was achieved using stereolithography 3D bioprinting technology. The printed skin microtissues were put into the self-designed 3D platform that integrated cell culture and electrochemical detection. The experimental results showed that the sensor could effectively detect FV when the optimized ratio of RBL-2H3 to MS1 cells and allergen stimulation time were 2:8 and 2 h, respectively. The linear detection range was 0.125-3.0 µg/mL, and the calculated lowest detection limit was 0.122 µg/mL. In addition, the sensor had excellent selectivity, specificity, stability, and reliability. Thus, this study successfully constructed a biomimetic skin microtissue electrochemical sensor for PV detection.

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This paper aimed to investigate the effects of exercise on hepatic platelet-activating factor (PAF) metabolism in rats fed a high-fat diet. Thirty-two male Sprague-Dawley (SD) rats were divided into control group (C), high-fat diet group (H), exercise group (EC), and high-fat diet+exercise group (EH). Serum lipids, glucose, insulin and markers of hepatic injury after a 16-week dietary and/or exercise intervention (60 min/day, 6 times/week) were measured by biochemical analysis; liver lipidomic profiles were analyzed by liquid chromatograph-mass spectrometer (LC-MS). Gene and protein expression of enzymes related to PAF metabolism were determined by qPCR and Western blot respectively. The results showed that high-fat diet feeding significantly increased the levels of low-density lipoprotein-cholesterol (LDL-C) and liver injury markers including purine nucleoside phosphorylase (PNP) and malondialdehyde (MDA) in rats, which were decreased by exercise. Furthermore, high-fat diet feeding significantly increased the hepatic PAF content, which was also attenuated by exercise. In addition, although high-fat diet treatment resulted in an increase in the expression of both PAF synthetase (PAF-CPT and PLA2) and hydrolase (Lp-PLA2 and PAF-AH(II)), induction of PAF synthetase was much greater than that of PAF hydrolase. While exercise increased the expression of Lp-PLA2 and PAF-AH(II) and decreased the expression of PAF-CPT and PLA2, key PAF synthesizing enzymes. In conclusion, high-fat diet-induced increase in hepatic PAF content is mainly due to the increase of its pathological synthesis at the translational level. Exercise reduces hepatic PAF content in high-fat fed rats by increasing PAF hydrolysis and decreasing its synthesis.

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This study aimed to evaluate the potential of capping protein (actin filament) muscle Z-line subunit ß (CAPZB) messenger ribonucleic acid (mRNA) levels as a biomarker for distinguishing low-grade squamous intraepithelial lesions of the cervix (LSIL) from high-grade squamous intraepithelial lesions of the cervix (HSIL). We collected a total of 166 cervical exfoliated cells and divided them into five groups based on histopathological results. Each sample was divided into two portions, one for fluorescence in situ hybridization (FISH) detection and the other for bisulfite sequencing polymerase chain reaction (BSP) detection. We found that FISH detection of CAPZB mRNA mean fluorescence intensity (MFI) and BSP detection of CAPZB deoxyribonucleic acid (DNA) percentage of methylation rate (PMR) performed as biomarkers for distinguishing HSIL from LSIL, with an area under the receiver operating characteristic curve (AUC), sensitivity, specificity and cut-off value of 0.893, 81.25%, 80.39% and 0.616, 0.794, 64.06%, 81.37% and 0.454, respectively. Furthermore, FISH detection of CAPZB mRNA exhibited a greater AUC (0.893) for the detection of HSIL than the CAPZB DNA methylation method (0.794), indicating the CAPZB mRNA levels can be used as a biomarker for assessing cervical lesions.

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Intersubband transition was recently discovered in colloidal nanoplatelets, but the associated intersubband carrier relaxation dynamics remains poorly understood. In particular, it is crucial to selectively excite the intersubband transition and to follow the hot electron dynamics in the absence of valence-band holes. This is achieved herein by exciting the predoped electrons in CdSe/ZnS nanoplatelets using near-infrared femtosecond pulses and monitoring nonequilibrium electron dynamics using broad-band visible pulses. We find that the n = 2 electrons relax to the n = 1 subband and establish a Fermi-Dirac distribution within 200 fs, and finally reach an equilibrium with the lattice within a few ps. The cooling dynamics depend mainly on the excitation fluence but weakly on the doping density and the lattice temperature. These characteristics are well captured by our numerical simulation that explicitly accounts for the state occupation effect and optical phonon scattering.

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This paper focuses on the cooperative driving challenges of connected and automated vehicles (CAVs) at single-lane roundabouts. First, a geometric path planning method is proposed for CAVs navigating a single-lane roundabout. Based on this method, a vehicle roundabout model is established. Four potential traffic scenarios for CAVs are established, and the optimal arrival times at conflict points are analyzed. By correlating the optimal arrival times at conflict points with the optimal entry times into the roundabout, the multi-vehicle coordination problem in complex intersections is simplified to a speed control issue during entry. Utilizing the principles of optimal control and Pontryagin minimization, two speed optimization strategies are proposed. Finally, MATLAB is employed for simulation analysis. The results indicate that the control strategy proposed in this paper enables the system to clearly identify potential conflicts between vehicles and implement an optimal control strategy, ensuring that vehicles can navigate the roundabout efficiently in terms of time and fuel without collisions. Additionally, the minimum time interval is established at 0.2 seconds to completely prevent vehicle collisions. In this study, the fusion problem involving two vehicles at a single conflict point is further expanded to encompass multiple vehicles at multiple conflict points. Thus, the efficient scheduling of multiple vehicles in single-lane roundabouts is realized.

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Background: The real-world clinical impact of mNGS on BALF in the respiratory intensive care unit (RICU) is not yet fully understood. Methods: We investigated the clinical impact of mNGS on BALF samples obtained from 92 patients admitted to the RICU over a 2-year period. We utilized both mNGS and culture methods to evaluate the effectiveness of mNGS in diagnosing pulmonary infections. The clinical impact of mNGS were evaluated by the clinician committees. Results: Among the 92 diagnosed patients, 78 cases (84.7 %) were determined to have infectious diseases caused by pathogenic microorganisms, and the bacterial infections constituted the most prevalent diagnostic category. For mixed infection, the most common type was the Pneumocystis jironecii and cytomegalovirus co-infection. The mNGS results had a positive impact on the clinical management of 43 cases (46.7 %). Moreover, 19 cases (44.2 %) of positive clinical impacts were solely based on new diagnoses made possible by mNGS results. These new diagnoses were particularly helpful for identifying rare pathogens, which could not be detected by conventional diagnostic methods. Conclusions: The BALF mNGS has a positive real-world impact in RICU. Clinician committee play a critical role in ensuring the appropriate use of mNGS.

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This paper presents a glint correction algorithm for high spatial resolution optical remote sensing imagery captured by the ER-2 Airborne Visual Infrared Imaging Spectrometer (AVIRIS). The algorithm employs linear and differential techniques to mitigate sun glint and sky glint effects, encompassing statistical glint reflections resulting from variations in imaging angles within strips and inter-strip variations due to Fresnel reflectance disparities. It aims to diminish Fresnel reflectance diversity on water surfaces and mitigate the distortions induced by glint reflectance during spectral and ocean color inversion. A comparative analysis of spectral and ocean color information in AVIRIS images before and after correction reveals enhanced accuracy following the glint correction. By systematically addressing multiple glint reflections and their ramifications, this method offers a valuable framework for correcting water surface glint in diverse high spatial resolution optical imagery.

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With the development and widespread application of electromagnetic technology, the health hazards of electromagnetic radiation have attracted much attention and concern. The effect of electromagnetic radiation on the nervous system, especially on learning, memory, and cognitive functions, is an important research topic in the field of electromagnetic biological effects. Most previous studies were conducted with rodents, which are relatively mature. As research has progressed, studies using non-human primates as experimental subjects have been carried out. Compared to rodents, non-human primates such as macaques not only have brain structures more similar to those of humans but also exhibit learning and memory processes that are similar. In this paper, we present a behavioral test system for the real-time evaluation of the working memory (WM) of macaques in a microwave environment. The system consists of two parts: hardware and software. The hardware consists of four modules: the operation terminal, the control terminal, the optical signal transmission, and detection module and the reward feedback module. The software program can implement the feeding learning task, the button-pressing learning task, and the delayed match-to-sample task. The device is useful for the real-time evaluation of the WM of macaques in microwave environments, showing good electromagnetic compatibility, a simple and reliable structure, and easy operation.

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Macadamia nuts are one of the most important economic food items in the world. Pericarp thickness and flavonoid composition are the key quality traits of Macadamia nuts, but the underlying mechanism of pericarp formation is still unknown. In this study, three varieties with significantly different pericarp thicknesses, namely, A38, Guire No.1, and HAES 900, at the same stage of maturity, were used for transcriptome analysis, and the results showed that there were significant differences in their gene expression profile. A total of 3837 new genes were discovered, of which 1532 were functionally annotated. The GO, COG, and KEGG analysis showed that the main categories in which there were significant differences were flavonoid biosynthesis, phenylpropanoid biosynthesis, and the cutin, suberine, and wax biosynthesis pathways. Furthermore, 63 MiMYB transcription factors were identified, and 56 R2R3-MYB transcription factors were clustered into different subgroups compared with those in Arabidopsis R2R3-MYB. Among them, the S4, S6, and S7 subgroups were involved in flavonoid biosynthesis and pericarp formation. A total of 14 MiMYBs' gene expression were verified by RT-qPCR analysis. These results provide fundamental knowledge of the pericarp formation regulatory mechanism in macadamia nuts.

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This study aims to investigate the influence of alkaline treatment duration (0-5 h) on the physicochemical properties and emulsifying performance of rapeseed protein during pH-shift process. Results showed that a 4-h alkaline treatment significantly reduced the particle size of rapeseed protein and led to a notable decrease in disulfide bond content, as well as alterations in subunit composition. Moreover, solubility of rapeseed protein increased from 18.10 ± 0.13% to 40.44 ± 1.74% post-treatment, accompanied by a âˆ¼ 40% enhancement in emulsifying properties. Morphological analysis revealed superior plasticity and sharper contours in 4-h alkali-treated rapeseed protein emulsions compared to untreated counterparts. Rheological analysis indicated higher viscosity and elasticity in the alkali-treated group. Overall, 4-h alkaline treatment markedly enhanced the multifaceted functional attributes of rapeseed protein during pH-shift process, rendering it a promising emulsifier in the food industry.

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Background: The Stenotrophomonas maltophilia complex (Smc) has emerged as a significant nosocomial pathogen contributing to increased mortality rates, particularly in case of bloodstream infections. Methods: This study employed whole-genome sequencing (WGS) to assess the genetic diversity, antimicrobial resistance profiles, molecular epidemiology and frequencies of virulence genes among 55 S. maltophilia isolates obtained from bacteremic cases over a 9-year period. Results: Based on the threshold of 95% average nucleotide identity (ANI) and 70% digital DNA-DNA hybridization (dDDH) for genospecies delineation, we classified 37 isolates into 6 known species, all belonging to the Smc. The remaining 18 isolates sequenced in this study were assigned to 6 new genomospecies. Among the 55 isolates, we identified 44 different sequence types (STs), comprising 22 known and 22 novel allele combinations. The resistance rate of Smc against trimethoprim-sulfamethoxazole (TMP/SMX) was found to be 3.6%, with the sul1 and class one integron integrase genes (intI) detected in these isolates. All Smc isolates were susceptible to minocycline. Furthermore, all Smc strains harbored the motA, pilU, smf-1 and Stmpr2 genes. Genomospecies 1 (100%, n = 9), Stenotrophomonas maltophilia (84.21%, n = 19) and Stenotrophomonas sepilia (71.43%, n = 7) demonstrated a higher percentage of the afaD gene, which was also associated with a higher separation rate. In addition to motA, pilU, smf-1, and Stmpr2 genes, all S. maltophilia strains (100%) contained entA, gspD, KatA, and stmPr1 genes, while all genomospecies 1 strains (100%) contained afaD, entA, gspD, and KatA genes. Conclusion: Our study highlights the genetic diversity among Smc isolates from patients with bacteremia, revealing 22 novel ST types, 58 new alleles and 6 new genomospecies. S. maltophilia and S. pavanii were found to carry more virulence factors, emphasizing the importance of accurate strain identification. Minocycline emerged as a promising alternative antibiotic for patients who were resistant to TMP/SMX.

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Obesity, characterized by its complexity and heterogeneity, has emerged as a significant public health concern. Its association with increased incidence and mortality of cardiovascular diseases stems not only from its complications and comorbidities but also from the endocrine effects of adipose tissue. Abdominal aortic aneurysm (AAA), a chronic inflammatory condition, has been closely linked to obesity. Intriguingly, mild obesity appears to confer a protective effect against AAA mortality, whereas severe obesity and being underweight do not, giving rise to the concept of the "obesity paradox". This review aims to provide an overview of obesity and its paradoxical relationship with AAA, elucidate its underlying mechanisms, and discuss the importance of preoperative weight loss in severely obese patients with AAA.

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BACKGROUND: Diabetic foot ulcer (DFU) is a chronic and challenging condition, addressed through various treatments including photodynamic therapy (PDT) and standard of care (SOC), yet lacking consensus on the optimal approach. This study presents a comprehensive meta-analysis of randomized controlled trials to evaluate the efficacy and safety of PDT versus SOC in managing DFU. METHODS: An extensive literature search was conducted across PubMed, Embase, and the Cochrane Library databases to identify RCTs that compared the effectiveness of PDT with SOC in treating DFU. The primary metrics evaluated included changes in ulcer area, wound healing indices, and pain levels experienced by the patients. RESULTS: This meta-analysis incorporated data from 6 RCTs, encompassing 458 patients with 467 DFUs. The analysis indicated that while PDT led to a faster reduction in ulcer size compared to SOC, the difference was not statistically significant [mean difference (MD): 2.73cm², 95 % Confidence Interval (CI) -2.98 to 8.44; p > 0.05]. However, a notable improvement was observed in the wound healing rate in the PDT group [MD: 29.26 %, 95 % CI 7.24 to 51.28; p = 0.01]. Based on the Visual Analog Scale (VAS), pain assessment revealed no significant difference between the two treatment groups [MD: 2.35, 95 % CI -2.36 to 7.06; p = 0.33]. CONCLUSION: The study suggests that PDT might offer an enhanced healing rate for DFUs compared to SOC alone, potentially leading to improved patient outcomes. Importantly, our findings highlight the superiority of photodynamic therapy in accelerating ulcer healing without an associated increase in complications. PROSPERO: 2023 CRD42023493930.

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BACKGROUND: The effects of heat acclimation (HA) on the hypothalamus after exertional heatstroke (EHS) and the specific mechanism have not been fully elucidated, and this study aimed to address these questions. METHODS: In the present study, rats were randomly assigned to the control, EHS, HA, or HA + EHS groups (n = 9). Hematoxylin and eosin (H&E) staining was used to examine pathology. Tandem mass tag (TMT)-based proteomic analysis was utilized to explore the impact of HA on the protein expression profile of the hypothalamus after EHS. Bioinformatics analysis was used to predict the functions of the differentially expressed proteins. The differential proteins were validated by western blotting. An enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines in the serum. RESULTS: The H&E staining (n = 5) results revealed that there were less structural changes in hypothalamus in the HA + EHS group compared with the EHS group. Proteomic analysis (n = 4) revealed that proinflammatory proteins such as argininosuccinate synthetase (ASS1), high mobility group protein B2 (HMGB2) and vimentin were evidently downregulated in the HA + EHS group. The levels of interleukin (IL)-1ß, IL-1, and IL-8 were decreased in the serum samples (n = 3) from HA + EHS rats. CONCLUSIONS: HA may alleviate hypothalamic damage caused by heat attack by inhibiting inflammatory activities, and ASS1, HMGB2 and vimentin could be candidate factors involved in the exact mechanism.

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Tau protein is a microtubule-associated protein that is widely distributed in the central nervous system and maintains and regulates neuronal morphology and function. Tau protein aggregates abnormally and forms neurofibrillary tangles in neurodegenerative diseases, disrupting the structure and function of neurons and leading to neuronal death, which triggers the initiation and progression of neurological disorders. The aggregation of tau protein in neurodegenerative diseases is associated with post-translational modifications, which may affect the hydrophilicity, spatial conformation, and stability of tau protein, promoting tau protein aggregation and the formation of neurofibrillary tangles. Therefore, studying the role of tau protein in neurodegenerative diseases and the mechanism of aberrant aggregation is important for understanding the mechanism of neurodegenerative diseases and finding therapeutic approaches. This review describes the possible mechanisms by which tau protein promotes neurodegenerative diseases, the post-translational modifications of tau protein and associated influencing factors, and the current status of drug discovery and development related to tau protein, which may contribute to the development of new therapeutic approaches to alleviate or treat neurodegenerative diseases.

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Macadamia nut plantings in China are expanding year by year. In order to breed and promote superior varieties, this study analyzed the effects of different rootstocks and scions on the survival rate of grafted seedlings, and then selected the best substrate composition for plant growth. The results showed that the survival rate of the HAES788 variety as rootstock and Guire No. 1 as scion was the highest, reaching 96%. The optimal grafting time in December was better than that in March. Furthermore, among 16 substrate formulations, T12, T13, T15, and T16 had advantages of agglomerated soil and more well-developed root systems compared to the CK made of loess. The plant height, stem diameter, leaf length, leaf width, and dry weight of the aboveground and underground parts of the grafted seedlings planted in these substrate formulations were significantly higher than those plants planted in the CK. In addition, the substrate formulations T12, T13, T15, and T16 significantly improved the organic matter, total nitrogen, and total potassium content of the substrate soils, but little improvement was observed for total phosphorus content after 13 months. Overall, macadamia grafting times are best in December, with HAES788 and Guire No. 1 being the best rootstock and scion. The optimal substrate formulations are T12, T13, T15, and T16. This study provides a solid foundation for the production of high-quality macadamia plants.