Improvements in the Magnesium Ion Transport Properties of Graphene/CNT-Wrapped TiO2 -B Nanoflowers by Nickel Doping.

Magnesium-ion batteries are widely studied for its environmentally friendly, low-cost, and high volumetric energy density. In this work, the solvothermal method is used to prepare titanium dioxide bronze (TiO2 -B) nanoflowers with different nickel (Ni) doping concentrations for use in magnesium ion batteries as cathode materials. As Ni doping enhances the electrical conductivity of TiO2 -B and promotes magnesium ion diffusion, the band gap of TiO2 -B host material can be significantly reduced, and as Ni content increases, diffusion contributes more to capacity. According to the electrochemical test, TiO2 -B exhibits excellent electrochemical performance when the Ni element doping content is 2 at% and it is coated with reduced graphene oxide@carbon nanotube (RGO@CNT). At a current density of 100 mA g-1 , NT-2/RGO@CNT discharge specific capacity is as high as 167.5 mAh g-1 , which is 2.36 times of the specific discharge capacity of pure TiO2 -B. It is a very valuable research material for magnesium ion battery cathode materials.

Causal relationships between peripheral immune cells and Alzheimer's disease: a two-sample Mendelian randomization study.

OBJECTIVE: Previous research suggests that peripheral immune cells may play a role in the development of Alzheimer's disease (AD). Our study aims to determine if the composition of peripheral immune cells directly contributes to the occurrence of AD. METHODS: We utilized a two-sample Mendelian randomization (MR) approach to examine the association between peripheral immune cells and AD.The primary analysis method used was the inverse variance weighted (IVW) method, and we also conducted analyses using MR Egger, weighted median, simple mode, and weighted mode methods to ensure the accuracy of the results.Heterogeneity and horizontal pleiotropy were evaluated using Cochran's Q statistics and the MR Egger intercept, respectively. RESULTS: The study found a significant correlation between increased IgD + CD24- AC cells (Odds Ratio [OR] = 1.03, 95% Confidence Interval [CI] = 1.01-1.06, P = 0.0172), increased CD4 + %leukocyte (OR = 1.08, 95% CI = 1.02-1.14, P = 0.0086), and increased CD4 + CD8dim AC cells (OR = 1.06, 95% CI = 1.01-1.11, P = 0.0218), with an increased susceptibility to AD. Conversely, an increase in EM DN (CD4-CD8-) %T cells (OR = 0.95, 95% CI = 0.92-0.99, P = 0.0164) and an increase in DN (CD4-CD8-) AC cells (OR = 0.93, 95% CI = 0.88-0.99, P = 0.0145) were associated with a protective effect against AD. CONCLUSION: Our findings establish a causal link between peripheral immune cells and AD. This study is the first to examine the relationship between peripheral immune cells and AD using MR, offering valuable insights for early diagnosis and treatment decisions.

Innovative all-organic dielectric composite for dielectric capacitor with great energy storage performance based on thermodynamic compatibility.

In modern electronics and power systems, good-performance dielectric capacitors have an essential function. Polymer-based dielectrics are widely used in the field of dielectric capacitors because of their large dielectric constant, flexibility, low density, and ease of processing. At present, ferroelectric polymers suffer from low breakdown field strength and high dielectric losses. How to improve the performance of dielectric materials in capacitors is still a promising research. This paper chooses the ferroelectric polymer poly(vinylidene fluoride) (PVDF) that worked as the matrix, and the linear polymers polyimide, cyanoethyl pullulan (CR-S), polyethersulfone, and cyanoethylated cellulose served as fillers. This all-organic dielectric composite produced as films working in electrostatic energy storage devices is prepared by using a casting method. Analyzing the test results, the composite film exhibited excellent electrical properties when the CR-S doping content was 5 wt. %. The organic composite dielectric based on CR-S/PVDF has a breakdown field strength of 450 MV/m, a discharge energy storage density (Ue) of 10.3 J/cm3, a high dielectric constant of 10.9, and a low dielectric loss of 0.004 at 1 kHz, which is a significant improvement compared with other dielectric composites. This all-organic dielectric composite strategy offers a new approach to achieve better-performance dielectric energy storage materials.

Total Flavonoids in Premna Fulva Craib Alleviates Brain Neurological Impairment and Influences Nrf2 and HO-1 Expressions in Rats with Ischemia-Reperfusion.

Total flavonoids in Premna fulva Craib (TFPFC) are a kind of flavonoid compound synthesized via photosynthesis extracted from Premna fulva Craib, which possess a strong anti-oxidative effect. Cerebral Ischemia-Reperfusion refers to the body's damage mainly caused by oxidative stress. This study aims to investigate the alleviating effect of TFPFC on brain neurological impairment and its influences on Nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) expressions in rats with Ischemia-Reperfusion. The rat model of Ischemia-Reperfusion was established, and rats were treated with TFPFC or normal saline. At 24 h after reperfusion, the neurological score, volume of cerebral infarction and cerebral water content were analyzed in different groups. The influences of TFPFC treatment on the proliferative activity and apoptosis of oxygen and glucose deprivation/reoxygenation (OGD/R) neural stem cells were detected via methyl thiazolyl tetrazolium (MTT) assay and flow cytometry. Moreover, the malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were measured to evaluate the oxidative stress effect. The influences of TFPFC treatment on the protein and messenger ribonucleic acid (mRNA) expressions of Nrf2 and HO-1 were analyzed using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. The TFPFC treatment alleviated the neurological impairment in rats after Ischemia-Reperfusion and reduced the volume of cerebral infarction and cerebral edema status in rats with Ischemia-Reperfusion. TFPFC increased the proliferative activity of OGD/R neural stem cells and decreased damage and apoptosis. In addition, the TFPFC treatment reduced the MDA level, improved the SOD activity, and up-regulated the protein and mRNA expressions of Nrf2 and HO-1. The TFPFC treatment may improve oxidative damage and protect the nervous system through the up-regulation of expressions of transcription factors Nrf2 and HO-1.

Detection method of springback for linear guideway straightening using digital image correlation.

The guideway deformation control of the straightening process is the basic method to ensure straightening accuracy. The prediction of and compensation for springback in the straightening process of a guideway adopts mostly numerical analysis and finite element analysis methods instead of experimental methods because of the measuring difficulty of actual springback. In this paper, a method is proposed to detect bending deformation during the straightening process, which provides a reference for the relevant manufacturing processes. Digital image correlation measurement technology is adopted for the detection of bending springback, which can measure the full-field displacement distribution without contact and with high precision. The experimental results show that digital image related technology can very accurately detect the deformation of the guideway straightening stroke and bending springback deformation. This study can help to control bending deformation during the straightening process and ensure straightening accuracy, providing a reference for real-time monitoring of straightening force.

Hexachloropentadiene in Soil, Air, and Biota Around an Agrochemical Factory: Concentrations, Distribution, and Risk Evaluation.

Hexachloropentadiene (HCPD) is a highly toxic compound that is mainly used for preparation of organochlorine insecticides. To investigate HCPD contamination of the environment during pesticide processing, 153 air, soil, and biota samples were collected around an agrochemical factory in different seasons of 1 year and analyzed for HCPD. The HCPD concentrations were 0.01-12.7 ng/m3 (average 2.60 ng/m3) in the air samples and 0.14-51.5 ng/g (average 4.11 ng/g) in the soil samples. HCPD concentrations were highest within 1 km north of the production site, which was in the downwind direction of the factory and storage tanks, especially in autumn and winter. Soil-air exchange analysis showed that HCPD was deposited from air to soil with a flux of 0.003 to 0.20 ng/(m2 d) throughout the year. The dismantling of obsolete equipment accelerated the release of HCPD into the air and increased the amount of HCPD deposited in the soil. HPCD concentration ranges were 0.44-55.7 ng/g dry weight [d.w.] (average 22.2 ng/g d.w.) and 6.69-91.4 ng/g d.w. (average 26.2) in locally grown rice and wheat, respectively. The concentration range was 12.1-1596 ng/g lipid weight (average 560 ng/g lipid weight) in local organisms, except for chicken. In tissues from locally raised chicken, the HCPD concentrations decreased in the order of gizzard, liver, heart, and meat. HCPD was amplified through a short food chain (soil, Vigna unguiculata leaves, larvae of Pieris rapae, and chicken), and the bioaccumulation factor gradually increased over a range of 1.19-25.1 (mean 9.81).

A Hybrid Landslide Displacement Prediction Method Based on CEEMD and DTW-ACO-SVR-Cases Studied in the Three Gorges Reservoir Area.

Accurately predicting the surface displacement of the landslide is important and necessary. However, most of the existing research has ignored the frequency component of inducing factors and how it affects the landslide deformation. Therefore, a hybrid displacement prediction model based on time series theory and various intelligent algorithms was proposed in this paper to study the effect of frequency components. Firstly, the monitoring displacement of landslide from the Three Gorges Reservoir area (TGRA) was decomposed into the trend and periodic components by complete ensemble empirical mode decomposition (CEEMD). The trend component can be predicted by the least square method. Then, time series of inducing factors like rainfall and reservoir level was reconstructed into high frequency components and low frequency components with CEEMD and t-test, respectively. The dominant factors were selected by the method of dynamic time warping (DTW) from the frequency components and other common factors (e.g., current monthly rainfall). Finally, the ant colony optimization-based support vector machine regression (ACO-SVR) is utilized for prediction purposes in the TGRA. The results demonstrate that after considering the frequency components of landslide-induced factors, the accuracy of the displacement prediction model based on ACO-SVR is better than that of other models based on SVR and GA-SVR.

Design and Testing of Inertial System for Landslide Displacement Distribution Measurement.

Landslide displacement monitoring plays a fundamental role in the study of landslide evolution mechanisms, forecasting, risk assessment, prevention, and control. To fill the deficiencies of traditional instrumentation for measuring landslide displacement distributed along lateral direction, a landslide displacement measurement method based on deformation-coupled pipeline trajectory measurement is proposed, and a pipeline trajectory inertial measurement instrument is developed. The developed instrument, primarily comprised of a single shaft gyro, two axis accelerometers, and an external roller encoder, is designed as an axial half strapdown-radial half platform structure combined with a mechanical gravity platform. This structure avoids the singularity of pitch angle and roll angle and can expediently calculate a pipeline trajectory with an Eulerian transformation when obtaining several basic physical variables, e.g., the axial linear velocity, pitch angle, roll angle, and azimuth angle. Additionally, the pipeline trajectory, measured at different times, possesses the ability to reflect the displacement evolution feature of landslides. The results of prototype simulation tests imply a single measurement accuracy of a 12 cm/100 m span and a singly periodic multiple (more than five times) measurement accuracy of a 3 cm/100 m span, which meets medium-precision displacement measurement requirements for a landslide. Additionally, the finished instrument has been successfully applied to the deformation monitoring of the Majiagou I# landslide, which further verifies its feasibility and offers a reference for similar landslides.

Salinity effects on elemental analysis in bulk water by laser-induced breakdown spectroscopy.

The effects of salinity on underwater laser-induced breakdown spectroscopy (LIBS) were investigated with salinities ranging from 2‰ to 50‰. Both spectroscopic and fast imaging techniques were used to observe plasma emission. It was shown that as the salinity increased, emission intensities of the atomic lines increased, while intensities of the ionic lines were suppressed. The signal-to-background ratios of the spectral lines decreased as a function of salinity, but the signal-to-noise ratios changed irregularly with salinity. Image results demonstrated that brighter and longer plasma could be produced at higher salinity with higher plasma temperature and electron density. The calibration curves at different salinities indicated that the high salinity environment did not limit the detection capability of LIBS. The obtained results reveal the significant influences of salinity on underwater LIBS detection, which plays an important role in promoting applications of LIBS in the ocean.

Synthesis of Triarylmethanes via Palladium-Catalyzed Suzuki Coupling of Trimethylammonium Salts and Arylboronic Acids.

An efficient palladium-catalyzed Suzuki coupling of 1,1-diarylmethyl-trimethylammonium triflates with arylboronic acids is reported. This reaction offers a novel approach to triarylmethane derivatives in good to excellent yields with the palladium-catalyzed C-N bond cleavage as the key feature. Broad substrate scope regarding both reaction partners are observed. Moreover, reactive functional groups such as vinyl and formyl groups are conserved in this transformation.

Design and Testing of a Flexible Inclinometer Probe for Model Tests of Landslide Deep Displacement Measurement.

The physical model test of landslides is important for studying landslide structural damage, and parameter measurement is key in this process. To meet the measurement requirements for deep displacement in landslide physical models, an automatic flexible inclinometer probe with good coupling and large deformation capacity was designed. The flexible inclinometer probe consists of several gravity acceleration sensing units that are protected and positioned by silicon encapsulation, all the units are connected to a 485-comunication bus. By sensing the two-axis tilt angle, the direction and magnitude of the displacement for a measurement unit can be calculated, then the overall displacement is accumulated according to all units, integrated from bottom to top in turn. In the conversion from angle to displacement, two spline interpolation methods are introduced to correct and resample the data; one is to interpolate the displacement after conversion, and the other is to interpolate the angle before conversion; compared with the result read from checkered paper, the latter is proved to have a better effect, with an additional condition that the displacement curve move up half the length of the unit. The flexible inclinometer is verified with respect to its principle and arrangement by a laboratory physical model test, and the test results are highly consistent with the actual deformation of the landslide model.

Neuronal ceroid lipofuscinosis with DNAJC5/CSPα mutation has PPT1 pathology and exhibit aberrant protein palmitoylation.

Neuronal ceroid lipofuscinoses (NCL) are a group of inherited neurodegenerative disorders with lysosomal pathology (CLN1-14). Recently, mutations in the DNAJC5/CLN4 gene, which encodes the presynaptic co-chaperone CSPα were shown to cause autosomal-dominant NCL. Although 14 NCL genes have been identified, it is unknown if they act in common disease pathways. Here we show that two disease-associated proteins, CSPα and the depalmitoylating enzyme palmitoyl-protein thioesterase 1 (PPT1/CLN1) are biochemically linked. We find that in DNAJC5/CLN4 patient brains, PPT1 is massively increased and mis-localized. Surprisingly, the specific enzymatic activity of PPT1 is dramatically reduced. Notably, we demonstrate that CSPα is depalmitoylated by PPT1 and hence its substrate. To determine the consequences of PPT1 accumulation, we compared the palmitomes from control and DNAJC5/CLN4 patient brains by quantitative proteomics. We discovered global changes in protein palmitoylation, mainly involving lysosomal and synaptic proteins. Our findings establish a functional link between two forms of NCL and serve as a springboard for investigations of NCL disease pathways.

Oligomerization of Cysteine String Protein alpha mutants causing adult neuronal ceroid lipofuscinosis.

Cysteine String Protein alpha (CSPα) is a palmitoylated, synaptic vesicle co-chaperone that is essential for neuroprotection. Two mutations in CSPα - L115R and L116Δ - cause adult neuronal ceroid lipofuscinosis (ANCL), a dominantly-inherited neurodegenerative disease. To elucidate the pathogenesis of ANCL, the intrinsic biochemical properties of human wildtype (WT) and disease mutant CSPα were examined. Mutant proteins purified from Escherichia coli exhibited high potency to oligomerize in a concentration, temperature, and time dependent manner, with L115R possessing the greatest potency. When freshly purified, ANCL mutant proteins displayed normal co-chaperone activity and substrate recognition similar to WT. However, co-chaperone activity was impaired for both CSPα mutants upon oligomerization. When WT and mutant CSPα were mixed together they co-oligomerized leading to an overall decrease of co-chaperone activity. The oligomerization properties of ANCL mutants were faithfully replicated in HEK 293T cells. Interestingly, the oligomers were covalently tagged by ubiquitination instead of palmitoylation. Taken together, ANCL mutations result in both a gain and partial loss-of-function.

Interleukin 35 is an independent prognostic factor and a therapeutic target for nasopharyngeal carcinoma.

AIM OF THE STUDY: Interleukin (IL)-35 is composed of two subunits: Epstein-Barr virus-induced gene 3 (EBI3) and IL-12p35. Recently, overexpression of IL-35 has been found in several types of cancers. However, its clinical significance in nasopharyngeal carcinoma is still obscure. We have studied the clinical significance of IL-35 expression and its correlation with outcome of nasopharyngeal carcinoma patients. MATERIAL AND METHODS: Interleukin 35 expression was investigated in 80 nasopharyngeal carcinoma cases by immunohistochemistry. Moreover, Fisher's exact test, Kaplan-Meier plots, and Cox proportional hazards regression were utilized to analyse these results. RESULTS: In the present study, IL-35 is highly expressed in the majority of nasopharyngeal carcinoma samples. EBI3 and p35 immunoreactivity in nasopharyngeal carcinoma samples was 67.5% and 51.3%, respectively. Both EBI3 and p35 expressions were significantly associated with advancement of tumour stage. In addition, EBI3 expression was also correlated with lymph node metastasis. Further analysis showed that EBI3 or p35 staining indicated unfavourable prognosis (p < 0.05). Multivariate analysis suggested EBI3 was an independent prognostic predictor (p < 0.05). CONCLUSIONS: Our results indicate for the first time that IL-35 is correlated with progression of nasopharyngeal carcinoma. Therefore, IL-35 may be a useful target for the treatment of nasopharyngeal carcinoma.

WIP1 regulates the proliferation and invasion of nasopharyngeal carcinoma in vitro.

Wild-type p53-induced phosphatase (WIP1) is overexpressed and functionally altered in multiple human malignancies. The present study investigated its abnormal expression and dysfunctions in nasopharyngeal carcinoma (NPC) in vitro. Here, analysis of WIP1 mRNA and protein in human NPC tissues revealed that both WIP1 messenger RNA (mRNA) and protein were elevated and were correlated with NPC clinical stage and metastasis in patients. In vitro experiments further showed that WIP1 inhibition led to a decrease in the proliferative ability of NPC CNE-2 and 5-8F cells accompanied by cell cycle arrest and increased apoptosis. In addition, WIP1 knockdown inhibited the invasiveness of CNE-2 and 5-8F cells and was associated with the down-regulation of the expression of matrix metallopeptidase 9 (MMP-9) mRNA and protein. Taken together, our data demonstrate that WIP1 regulates the proliferation and invasiveness of NPC cells in vitro, and this may be correlated with its modulation of MMP-9 expression, cell cycle progression and apoptosis. WIP1 functioned as a potential therapeutic target in NPC management.

Study of the Dielectric and Corona Resistance Properties of PI Films Modified with Fluorene Moiety/Aluminum Sec-Butoxide.

With the policy tilt and increased investment in research and development in the world, new energy vehicle technology continues to progress and the drive motor power density continues to improve, which puts forward higher requirements for the comprehensive performance of the core insulating material enameled wire enamel for drive motors. Polyimide (PI) has excellent electrical insulation properties, and heat resistance is often used to drive the motor winding insulation. To further improve the corona resistance and insulating properties of PI wire enamel varnish, in this paper, firstly, fluorene groups with a rigid conjugated structure were introduced into the molecular chain of the PI film by molecular structure modulation, and then uniformly dispersed alumina nanoclusters (AOCs) were introduced into the PI matrix by using an in situ growth process to inhibit the migration of high-energy electrons. The quantum size effect of the alumina nanoclusters was exploited to synergistically enhance the suppression and scattering of energetic moving electrons by PI-based composite films. The results show that the breakdown field strength of the PI-based composite film (MPI/1.0 vol% AOC) reaches 672.2 kV/mm, and the corona resistance life reaches 7.9 min, which are, respectively, 1.55 and 2.19 times higher than those of the initial PI film. A PI-based composite film with excellent insulating and corona resistance properties was obtained.

Liver transcriptome and physiological analyses preliminarily revealed the adaptation mechanisms of Amur grayling (Thymallus arcticus grubei, Dybowski, 1869) fry for dietary lipid nutrition.

The Amur grayling (Thymallus arcticus grubei Dybowski, 1869), a species of potentially economic and research value, is renowned for its tender meat, exquisite flavor, and high nutritional contents. This study was conducted to investigate the physiological adaptation mechanisms to dietary lipids in Amur grayling fry (with average initial weight 4.64±0.03 g). This study involved a 56-day feeding trial with diets containing varying lipid levels (9.07%, 12.17%, 15.26%, 18.09%, 21.16%, and 24.07%, designated as GL1 through GL6, respectively) to explore the impact of dietary lipids on growth performance, intestinal digestion, liver antioxidative function, and transcriptomic profiles. Results showed that The group receiving 18% dietary lipid exhibited a markedly higher weight gain rate (WGR) and specific growth rate compared to other groups, alongside a reduced feed conversion ratio (FCR), except in comparison to the 15% lipid group. Activities of lipase in pancreatic secretion and amylase in stomach mucosa peaked in the 18% lipid treatment group, indicating enhanced digestive efficiency. The liver of fish in this group also showed increased activities of antioxidative enzymes and higher levels of glutathione and total antioxidative capacity, along with reduced malondialdehyde content compared to the 9% and 24% lipid treatments. Additionally, serum high-density lipoprotein cholesterol levels were highest in the 18% group. Transcriptomic analysis revealed four significant metabolic pathways affected: Cholesterol metabolism, Fat digestion and absorption, PPAR signaling, and Fatty acid degradation, involving key genes such as Lipase, Lipoprotein lipase, Fatty acid-binding protein, and Carnitine palmitoyltransferase I. These findings suggest that the liver of Amur grayling employs adaptive mechanisms to manage excessive dietary lipids. Quadratic regression analysis determined the optimal dietary lipid levels to be 16.62% and 16.52%, based on WGR and FCR, respectively. The optimal dietary lipid level for juvenile Amur grayling appears to be around 18%, as evidenced by improved growth performance, digestive function, balanced serum lipid profile, and enhanced liver antioxidative capacity. Exceeding this lipid threshold triggers both adaptive and potentially detrimental liver responses.

A canine model of femoral head osteonecrosis induced by an ethanol injection navigated by a novel template.

There is no consensus on how to establish models of osteonecrosis of the femoral head (ONFH) in large mammals. The aim of this study was to investigate the effectiveness of a novel canine model of ONFH, induced by a navigated injection of absolute ethanol. Using three-dimensional reconstruction and rapid prototyping manufacturing techniques, a new template was designed and processed to navigate the ethanol injection. The femoral heads of 18 adult dogs were injected with ethanol. Macroscopic, X-ray and histological examinations were performed at 3, 6, and 9 weeks after the operation. Further, computed tomography (CT), magnetic resonance imaging (MRI), and radionuclide scans were performed 6 weeks postoperatively. Three weeks after the operation, the femoral heads showed evidence of osteonecrosis including increasing numbers of empty lacunae, decreased hematopoietic cells, and destroyed adipose tissue in the medullary cavity, which increased in severity at the subsequent follow-up evaluations at 6 and 9 weeks. Fractured trabeculae and fibrous tissue were noted 9 weeks postoperatively. Image analysis also revealed evidence of osteonecrosis, such as several osteopenic areas with sclerotic rims on the X-ray, several areas of low bone mineral density with sclerosis on the CT scan, increased uptake of the nuclide species in MRI, and an inhomogeneous long T2 signal on the radioisotopic images. Ethanol injection navigated by our novel template was successful in establishing a canine model of ONFH. This model can be used to test new treatment modalities for human ONFH.

Porous titanium-6 aluminum-4 vanadium cage has better osseointegration and less micromotion than a poly-ether-ether-ketone cage in sheep vertebral fusion.

Interbody fusion cages made of poly-ether-ether-ketone (PEEK) have been widely used in clinics for spinal disorders treatment; however, they do not integrate well with surrounding bone tissue. Ti-6Al-4V (Ti) has demonstrated greater osteoconductivity than PEEK, but the traditional Ti cage is generally limited by its much greater elastic modulus (110 GPa) than natural bone (0.05-30 GPa). In this study, we developed a porous Ti cage using electron beam melting (EBM) technique to reduce its elastic modulus and compared its spinal fusion efficacy with a PEEK cage in a preclinical sheep anterior cervical fusion model. A porous Ti cage possesses a fully interconnected porous structure (porosity: 68 ± 5.3%; pore size: 710 ± 42 µm) and a similar Young's modulus as natural bone (2.5 ± 0.2 GPa). When implanted in vivo, the porous Ti cage promoted fast bone ingrowth, achieving similar bone volume fraction at 6 months as the PEEK cage without autograft transplantation. Moreover, it promoted better osteointegration with higher degree (2-10x) of bone-material binding, demonstrated by histomorphometrical analysis, and significantly higher mechanical stability (P < 0.01), shown by biomechanical testing. The porous Ti cage fabricated by EBM could achieve fast bone ingrowth. In addition, it had better osseointegration and superior mechanical stability than the conventional PEEK cage, demonstrating great potential for clinical application.

Serum proteomics identifies S100A11 and MMP9 as novel biomarkers for predicting the early efficacy of sublingual immunotherapy in allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a chronic inflammatory disorder, and sublingual immunotherapy (SLIT) is an important therapy. However, SLIT exhibits a wide range of fluctuations and lacks objective monitoring indicators. Therefore, exploring biomarkers for early prediction of the efficacy of SLIT is urgently needed. METHODS: We recruited two independent cohorts. In the discovery cohort, house dust mite (HDM) -induced AR patients underwent SLIT for at least 1 year, and were categorized into response and no response groups based on early efficacy. Serum proteomics was conducted to detect variations in protein expression levels between the two groups. The candidate proteins were confirmed in the validation cohort with enzyme-linked immunosorbent assay (ELISA), and their predictive values and levels of change before and after treatment were evaluated. RESULTS: Serum proteomics identified a total of 113 differential proteins between the two groups, including 41 proteins upregulated and 72 downregulated in the no response group than the response group. The top 5 up- and down-regulated proteins were selected for further validation, and ELISA results revealed that serum CCL14, LTA4H, S100A11 and MMP9 levels were significantly elevated, and TGFBI and MASP1 were decreased in the response group than those in the no response group(P < 0.05). Moreover, receiver operating characteristic curves revealed that serum S100A11 and MMP9 exhibited greater ability in predicting the early effectiveness of SLIT (AUC > 0.7, P < 0.05). Furthermore, these two biomarkers exhibited significant reductions 1 year after SLIT, particularly in those patients who responded positively to the treatment (P < 0.05). CONCLUSION: Serum S100A11 and MMP9 have the potential to serve as biomarkers for early prediction of the effectiveness of SLIT and monitoring the therapeutic effects. The circulating proteomic alterations might contribute to guiding treatment and understanding the mechanism of SLIT in AR patients.