Research on mix design and mechanical performances of MK-GGBFS based geopolymer pastes using central composite design method.

In order to alleviate environmental problems and reduce CO2 emissions, geopolymers had drew attention as a kind of alkali-activated materials. Geopolymers are easier access to raw materials, green and environment friendly than traditional cement industry. Its special reaction mechanism and gel structure show excellent characteristics such as quick hardening, high strength, acid and alkali resistance. In this paper, geopolymer pastes were made with metakaolin (MK) and ground granulated blast furnace slag (GGBFS) as precursors. The effects of liquid-solid ratio (L/S) and modulus of sodium silicate (Ms) on the performances of MK-GGBFS based geopolymer paste (MSGP) were characterized by workability, strength and microstructural tests. The regression equations were obtained by central composite design method to optimize the mix design of MSGP. The goodness of fit of all the equations were more than 98%. Based on the results of experiments, the optimum mix design was found to have L/S of 0.75 and Ms of 1.55. The workability of MSGP was significantly improved while maintaining the strength under the optimum mix design. The initial setting time of MSGP decreased by 71.8%, while both of the fluidity and 28-d compressive strength increased by 15.3%, compared with ordinary Portland cement pastes. Therefore, geopolymers are promising alternative cementitious material, which can consume a large amount of MK and GGBFS and promote green and clean production.

Prediction model of land surface settlement deformation based on improved LSTM method: CEEMDAN-ICA-AM-LSTM (CIAL) prediction model.

The uneven settlement of the surrounding ground surface caused by subway construction is not only complicated but also liable to cause casualties and property damage, so a timely understanding of the ground settlement deformation in the subway excavation and its prediction in real time is of practical significance. Due to the complex nonlinear relationship between subway settlement deformation and numerous influencing factors, as well as the existence of a time lag effect and the influence of various factors in the process, the prediction performance and accuracy of traditional prediction methods can no longer meet industry demands. Therefore, this paper proposes a surface settlement deformation prediction model by combining noise reduction and attention mechanism (AM) with the long short-term memory (LSTM). The complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and independent component analysis (ICA) methods are used to denoise the input original data and then combined with AM and LSTM for prediction to obtain the CEEMDAN-ICA-AM-LSTM (CIAL) prediction model. Taking the settlement monitoring data of the construction site of Urumqi Rail Transit Line 1 as an example for analysis reveals that the model in this paper has better effectiveness and applicability in the prediction of surface settlement deformation than multiple prediction models. The RMSE, MAE, and MAPE values of the CIAL model are 0.041, 0.033 and 0.384%; R2 is the largest; the prediction effect is the best; the prediction accuracy is the highest; and its reliability is good. The new method is effective for monitoring the safety of surface settlement deformation.

Study on mechanical properties of interbedded rock masses with microcrack based on thermal-mechanical coupling.

The mechanical properties of deep rock masses are significantly influenced by temperature and other factors. The effect of temperature on the strength of deep rock masses will pose a serious challenge to deep resource exploitation and engineering construction. In this paper, the thermal-mechanical coupling calculation model is established by particle flow code (PFC2D) to study the uniaxial compression response of rock masses with microcracks after temperature load. The strength of failure, microcracks, and strain was analyzed. The results show that: (i) When the soft rock thickness ratio Hs/H < 0.5, the displacement caused by the applied temperature is concentrated at the structural plane, and the contact force is concentrated at the end of the initial microcrack. When Hs/H ≥ 0.5, the displacement caused by the applied temperature is concentrated on both sides of the initial microcrack, and the contact force is concentrated in the hard rock area. (ii) The number of microcracks decreases with the increase of soft rock thickness under different working conditions. When the soft rock thickness ratio Hs/H < 0.5, the relationship curve between the number of microcracks and the vertical strain shows two stages of change. When Hs/H ≥ 0.5, the relationship curve between the number of cracks and the vertical strain changes shows three stages of change. (iii) When the soft rock thickness ratio Hs/H < 0.5, the failure strength decreases with the increase of soft rock thickness ratio at T = 100°C and 200°C. When T = 300°C and 400°C, the failure strength decreased first and then increased. When Hs/H ≥ 0.5, the failure strength increases with the increase of soft rock thickness at T = 200°C, 300°C, and 400°C. At T = 100°C, the failure strength decreases with the increase of soft rock thickness.

Research on Performance Deterioration of Multi-Walled Carbon Nanotube-Lithium Slag Concrete under the Coupling Effect of Sulfate Attack and Dry-Wet Cycles.

Sulfate attack is one of the main factors affecting the durability of concrete structures. In recent years, multi-walled carbon nanotubes (MWCNTs) have attracted the attention of scholars for their excellent mechanical properties and durability performance. In this paper, the influence of sulfate attack and dry-wet cycles on the performance of multi-walled carbon nanotube-lithium slag concrete (MWCNT-LSC) with varied MWCNT content (0 wt.%, 0.05 wt.%, 0.10 wt.%, and 0.15 wt.%) and varied water-cement ratios (0.35, 0.40, and 0.45) were investigated. In addition, scanning electron microscopy (SEM) and X-ray computed tomography (CT) tests were conducted to analyze the microstructure and pore structure of the concrete. The results showed that concrete incorporated with MWCNTs could effectively mitigate sulfate attack. The resistance to sulfate attack of concrete was negatively related to the water-cement ratio when the dry-wet cycle was fixed. The MWCNT-LSC showed the best compressive strength at the water-cement ratio of 0.35 and 0.10 wt.% MWCNTs. The SEM test results showed that the MWCNTs filled the pores and cracks within the specimen and formed bridges between the cracks, enhancing the resistance to sulfate attack. The CT test results also showed that the addition of MWCNTs could reduce the porosity of concrete, refine the pore size and inhibit the generation and development of cracks, thus optimizing the internal structure of concrete and improving its resistance to sulfate attack.

DEM modeling direct shearing behavior of sand considering anti-rotation of particle.

Considering anti-rotation of sand particles, two-dimensional Discrete Element Method (DEM) has been employed to reproduce direct shear behaviors of sand with different particle distribution sizes, so as to explore effects of anti-rotation of particle on responses of stress-displacement and dilatancy, the evolution law of shear stress, coordination number and vertical displacement of sand samples, and analyze the contact force chain, contact fabric and porosity of the samples after shearing.The results show that the anti-rotation ability of sand is enhanced, the torque of overcoming the relative rotation between particles is increased, and the peak shear stress, dilatancy and porosity in the middle of the sample are increased; with the increase of the anti-rotation coefficient, the coordination number decreases more obviously. The proportion of the contact number in the direction of 100°-160° to the total contact number decreases with the increase of the anti-rotation coefficient. The elliptical shape of the contact configuration becomes more flat, and the anisotropy of the contact force chain is more obvious; compared with fine sand, the coarse sand has greater shear capacity, more obvious dilatancy and larger porosity in the middle of the sample.The maximum minimum particle size ratio of the sample becomes larger, so that the shear strength of the sample is reduced, and the dilatancy is also weak.

Cracks propagation characteristics of double-hole delay blasting in soft-hard composite rock mass.

By researching the distance between blasthole and interface of soft-hard rock strata, as well as the time of delay detonation, blasting effect of the rock mass will be more controllable. Firstly, validity of numerical method was authenticated from three angles: blasting coupled stress field, ratio of crushing zone radius to blasthole radius, and crack network state. Under the condition of soft-hard rock strata, numerical model of double-hole blasting was established by using PFC2D. Then delay blasting experiments were carried out under different relative positions of blasthole and interface. Ultimately, results were analyzed from three perspectives: crack network, crack quantity and rock fragment. Results show that: (1) When detonated in hard rock, if between interface and blasthole distance is greater than twice crushing zone radius, the closer blasthole is to the interface, the more obvious the "hook" phenomenon between the two blastholes is. With increasing delayed initiation time, "hook" phenomenon will weaken or even disappear. (2) Based on the crack information initiated in hard rock, the law of crack number varying with thickness of hard rock and delay time is obtained. (3) For initiation in hard rock, crack extension range is large, but less fragments are formed. The law is opposite to that initiation in structural plane and soft rock. Fragmentation area increases exponentially with increasing soft rock thickness, and exponential function is obtained.

Seismic performance of a new precast concrete frame joint with a built-in disc spring.

A new, precast concrete frame beam-column connection is designed in this research. The connection adopts the assembly mode of the precast column and seam area jointly to maintain the integrity of the joint area and increase the assembly efficiency. Based on the conventional grouting sleeve connection, a disc spring device is constructed on the beam end to improve the ductility of the joint. Ten connecting specimens were tested under low cyclic loads, including two monolithic connections, four ordinary precast connections, and four new precast connections. The test parameters included the joint type and axial pressure ratio, and the difference in the seismic performance was determined by evaluating the failure mode, hysteresis characteristics, stiffness degradation, energy dissipation, and shear deformation of the joint area. Compared to monolithic connections, conventional precast connections display similar hysteresis characteristics. Although their ductility is slightly lower, their bearing capacity is higher. Compared with the previous two connections, the new connection with the built-in disc spring device has superior seismic performance. The axial pressure ratio is a significant aspect in determining the failure mode of the precast connection, and the specimen exhibits less shear damage at a larger axial pressure ratio.

Study of snow cover/depth evolution characteristics in Tianshan region of China based on geographical partition.

Based on the digital elevation data, snow depth and snow cover remote sensing data, this paper divides six snow evolution areas and geographical partitions, extracts the geographical partitions of each evolution area and obtains the geographical characteristics of the evolution area for analysis. The results show that: (1) From 2003 to 2017, the average snow area decreased at a rate of - 0.004, and the average snow depth increased at a rate of 0.03. (2) The snow in the middle altitude hill with shady gentle slope area is the most obvious in the seasonal evolution, and the percentage of this region in the seasonal snow evolution area is 5.46%, the snow depth in the middle altitude hill with sunny and gentle slopes area increased and decreased significantly in the past 15 years, and the percentage of this region in the SD significant changes evolution area was 6.32%. The snow in the low relief middle altitude mountain with shady and moderate slope area not only shows obvious seasonal evolution, but also increases and decreases significantly in snow depth. And the percentage of this region in the seasonal snow significant evolution area is 5.82%. (3) The geographical partitions with the largest area in all evolution areas is the middle altitude hill with sunny and gentle slopes area (4.75%). (4) The geographical partition with the largest variation of snow depth in Tianshan region is the low relief middle altitude mountain with shady and moderate slope area (12.02 cm). (5) The snow accumulation and melting are obvious in the range of 1000-3500 m above altitude, different geomorphology types lead to obvious differences in snow characteristics. The snow melting is most obvious in the gentle slope area of the low topographic relief geomorphology types, and the snow accumulation is most obvious in the steep slope area of the middle relief geomorphology types.

Numerical simulation of size effect of defective rock under compression condition.

The existence of various types of damage, small cracks, some large voids and the size of the sample in the rock will make the experimental results show great discreteness. In this paper, based on the results of laboratory experiments, a numerical model of large flawed rock samples is established by using particle flow software PFC2D, and the mechanical response of rocks with different length-diameter ratios and different flaw positions in uniaxial compression experiments is discussed. The results show that the specimen size has a significant effect on the crack characteristics, mechanical characteristics and energy characteristics of rock mass. From the perspective of energy and crack characteristics, the total number of cracks after the failure of the defective rock sample is slightly lower than that of the intact rock sample, resulting in a slightly lower peak strain energy during the rock failure process. From the mechanical properties of rock samples, the Poisson's ratio of intact rock samples is slightly smaller than that of defective rock samples. The strength of the defective sample is weakened relative to the complete rock sample, and the relationship formula between the weakening range and the aspect ratio is obtained through analysis. Moreover, different defect locations lead to different crack processes and crack modes, resulting in different uniaxial compressive strength.

One-Part Alkali-Activated Materials: State of the Art and Perspectives.

Alkali-activated materials (AAM) are recognized as potential alternatives to ordinary Portland cement (OPC) to limit CO2 emissions and beneficiate several wastes into useful products. Compared with its counterparts involving the concentrated aqueous alkali solutions, the development of "just add water" one-part alkali-activated materials (OP-AAM) has drawn much attention, mainly attributed to their benefits in overcoming the hazardous, irritating, and corrosive nature of activator solutions. This study starts with a comprehensive overview of the OP-AAM; 89 published studies reported on mortar or concrete with OP-AAM were collected and concluded in this paper. Comprehensive comparisons and discussions were conducted on raw materials, preparation, working performance, mechanical properties, and durability, and so on. Moreover, an in-depth comparison of different material pretreatment methods, fiber types, and curing methods was presented, and their potential mechanisms were discussed. It is found that ground granulated blast-furnace slag (GGBS) provides the best mechanical properties, and the reuse of most aluminosilicate materials can improve the utilization efficiency of solid waste. The curing temperature can be improved significantly for precursor materials with low calcium contents. In order to overcome the brittleness of the AAM, fiber reinforcement might be an efficient way, and steel fiber has the best chemical stability. It is not recommended to use synthetic fiber with poor chemical stability. Based on the analysis of current limitations, both the recommendations and perspectives are laid down to be the lighthouse for further research.

Mechanical properties and acoustic emission analysis of desert sand concrete reinforced with steel fiber.

In this study, to reduce the consumption of natural sand and improve the utilization rate of desert sand in western China, while preparing 14 groups of samples, desert sand is used to replace natural sand by the ratio of 20%, 40%, and 60%, and steel fiber is mixed with volume fraction 0.5%, 1.0%, 1.5%, and 2.0%. The mechanical properties of the specimens, including compressive strength, splitting tensile strength, and axial compressive strength were tested. Besides, the microstructures of the samples were analyzed by SEM, XRD, and acoustic emission detection technologies to identify the damage process. The results show that the desert sand can refine the microstructure and fill the pores, and it has good comprehensive properties at a 40% substitution rate. The compression properties of specimens are not apparently improved, but the tensile strength and deformation properties are significantly improved. The steel fiber with 1.5 vol% content behaves better, and the 28d compressive strength of the optimized group reaches 58.7 MPa. As a result, the polynomial fitting degree of total AE hits and stress level receives a more incredible goodness (R2) value than 0.96. The strength characteristics of steel fiber-desert sand concrete (SFDSC) can meet the demands of C40 concrete, and this research can provide a reference for engineers using desert sand in their designs.

Productivity and quality improvement for a symmetric bispecific antibody through the application of intensified perfusion cell culture.

Background: Aggregation, fragmentation, and low yield are issues frequently found during the cell culture process of bispecific antibodies (bsAbs), whose inherent complexity likely plays a role in causing these issues. Methods: In this study, we made a head-to-head comparison between fed-batch cell culture and intensified perfusion cell culture with a symmetric bsAb case. Results: In comparison with the fed-batch culture, a 6.6-fold improvement in integrated viable cell density and a 10.9-fold improvement in volumetric productivity were achieved with the intensified perfusion mode. In addition, a significant decrease in aggregation and fragmentation was observed with the intensified perfusion cell culture. Furthermore, product homogeneity was improved, which was reflected by the increased percentage of capillary isoelectric focusing main group. The quality improvement with intensified perfusion cell culture can be attributed to the shortened product retention in the bioreactor. Conclusions: These findings suggest that intensified perfusion cell culture could be a better choice than traditional fed-batch especially for complex molecules like bsAbs. As this is a single case report, future studies on other cases are needed to further confirm the general applicability of this strategy.

Enhanced removal of ammonium from water by ball-milled biochar.

Novel biochar was prepared by ball milling using bamboo as raw material. The aim of this study was to find a good alternative way to improve the potentials of biochar for ammonium adsorption from aqueous solution. The sorption performance of ball-milled bamboo biochar (BMBB) was compared with that of bamboo biochar (BB) using batch adsorption experiments. Different adsorption kinetics models proved that the pseudo-second order was the best kinetic model for explanation of the adsorption kinetics characteristics, indicative of the energetically heterogeneous solid surface of the biochar. The Langmuir model could fit the isothermal adsorption data of BMBB well. The maximum adsorption capacity of BMBB (22.9 mg g-1) was much higher than that of BB (7.0 mg g-1). This study offers a relatively cost-effective and efficient methodology for the improvement in the adsorption capacity of biochar for ammonium nitrogen.

The Tartary Buckwheat Genome Provides Insights into Rutin Biosynthesis and Abiotic Stress Tolerance.

Tartary buckwheat (Fagopyrum tataricum) is an important pseudocereal crop that is strongly adapted to growth in adverse environments. Its gluten-free grain contains complete proteins with a well-balanced composition of essential amino acids and is a rich source of beneficial phytochemicals that provide significant health benefits. Here, we report a high-quality, chromosome-scale Tartary buckwheat genome sequence of 489.3 Mb that is assembled by combining whole-genome shotgun sequencing of both Illumina short reads and single-molecule real-time long reads, sequence tags of a large DNA insert fosmid library, Hi-C sequencing data, and BioNano genome maps. We annotated 33 366 high-confidence protein-coding genes based on expression evidence. Comparisons of the intra-genome with the sugar beet genome revealed an independent whole-genome duplication that occurred in the buckwheat lineage after they diverged from the common ancestor, which was not shared with rosids or asterids. The reference genome facilitated the identification of many new genes predicted to be involved in rutin biosynthesis and regulation, aluminum stress resistance, and in drought and cold stress responses. Our data suggest that Tartary buckwheat's ability to tolerate high levels of abiotic stress is attributed to the expansion of several gene families involved in signal transduction, gene regulation, and membrane transport. The availability of these genomic resources will facilitate the discovery of agronomically and nutritionally important genes and genetic improvement of Tartary buckwheat.

Characterization and site-directed mutagenesis of an α-galactosidase from the deep-sea bacterium Bacillus megaterium.

A novel gene (BmelA) (1323bp) encoding an α-galactosidase of 440 amino acids was cloned from the deep-sea bacterium Bacillus megaterium and the protein was expressed in Escherichia coli BL21 (DE3) with an estimated molecular mass of about 45 kDa by SDS-PAGE. The enzyme belongs to glycoside hydrolase family 4, with the highest identity (74%) to α-galactosidase Mel4A from Bacillus halodurans among the characterized α-galactosidases. The recombinant BmelA displayed its maximum activity at 35 °C and pH 8.5-9.0 in 50 mM Tris-HCl buffer, and could hydrolyze different substrates with the Km values against p-nitrophenyl-α-D-galactopyranoside (pNP-α-Gal), raffinose and stachyose being 1.02±0.02, 2.24±0.11 and 3.42±0.17 mM, respectively. Besides, 4 mutants (I38 V, I38A, I38F and Q84A) were obtained by site-directed mutagenesis based on molecular modeling and sequence alignment. The kinetic analysis indicated that mutants I38 V and I38A exhibited a 1.7- and 1.4-fold increase over the wild type enzyme in catalytic efficiency (k(cat)/K(m)) against pNP-α-Gal, respectively, while mutant I38F showed a 3.5-fold decrease against pNP-α-Gal and mutant Q84A almost completely lost its activity. All the results suggest that I38 and Q84 sites play a vital role in enzyme activity probably due to their steric and polar effects on the predicted "tunnel" structure and NAD+ binding to the enzyme.

A novel cold-active and salt-tolerant α-amylase from marine bacterium Zunongwangia profunda: molecular cloning, heterologous expression and biochemical characterization.

A novel gene (amyZ) encoding a cold-active and salt-tolerant α-amylase (AmyZ) was cloned from marine bacterium Zunongwangia profunda (MCCC 1A01486) and the protein was expressed in Escherichia coli. The gene has a length of 1785 bp and encodes an α-amylase of 594 amino acids with an estimated molecular mass of 66 kDa by SDS-PAGE. The enzyme belongs to glycoside hydrolase family 13 and shows the highest identity (25%) to the characterized α-amylase TVA II from thermoactinomyces vulgaris R-47. The recombinant α-amylase showed the maximum activity at 35 °C and pH 7.0, and retained about 39% activity at 0 °C. AmyZ displayed extreme salt tolerance, with the highest activity at 1.5 M NaCl and 93% activity even at 4 M NaCl. The catalytic efficiency (k cat/K m) of AmyZ increased from 115.51 (with 0 M NaCl) to 143.30 ml mg(-1) s(-1) (with 1.5 M NaCl) at 35 °C and pH 7.0, using soluble starch as substrate. Besides, the thermostability of the enzyme was significantly improved in the presence of 1.5 M NaCl or 1 mM CaCl2. AmyZ is one of the very few α-amylases that tolerate both high salinity and low temperatures, making it a potential candidate for research in basic and applied biology.

MicroRNA profiling of primary cutaneous large B-cell lymphomas.

Aberrant expression of microRNAs is widely accepted to be pathogenetically involved in nodal diffuse large B-cell lymphomas (DLBCLs). However, the microRNAs profiles of primary cutaneous large B-cell lymphomas (PCLBCLs) are not yet described. Its two main subtypes, i.e., primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) and primary cutaneous follicle center lymphoma (PCFCL) are characterized by an activated B-cell (ABC)-genotype and a germinal center B-cell (GCB)-genotype, respectively. We performed high-throughput sequencing analysis on frozen tumor biopsies from 19 cases of PCFCL and PCLBCL-LT to establish microRNA profiles. Cluster analysis of the complete microRNome could not distinguish between the two subtypes, but 16 single microRNAs were found to be differentially expressed. Single microRNA RT-qPCR was conducted on formalin-fixed paraffin-embedded tumor biopsies of 20 additional cases, confirming higher expression of miR-9-5p, miR-31-5p, miR-129-2-3p and miR-214-3p in PCFCL as compared to PCLBCL-LT. MicroRNAs previously described to be higher expressed in ABC-type as compared to GCB-type nodal DLBCL were not differentially expressed between PCFCL and PCLBCL-LT. In conclusion, PCFCL and PCLBCL-LT differ in their microRNA profiles. In contrast to their gene expression profile, they only show slight resemblance with the microRNA profiles found in GCB- and ABC-type nodal DLBCL.

Genome-wide microRNA expression analysis of clear cell renal cell carcinoma by next generation deep sequencing.

MicroRNAs (miRNAs), non-coding RNAs regulating gene expression, are frequently aberrantly expressed in human cancers. Next-generation deep sequencing technology enables genome-wide expression profiling of known miRNAs and discovery of novel miRNAs at unprecedented quantitative and qualitative accuracy. Deep sequencing was performed on 11 fresh frozen clear cell renal cell carcinoma (ccRCC) and adjacent non-tumoral renal cortex (NRC) pairs, 11 additional frozen ccRCC tissues, and 2 ccRCC cell lines (n = 35). The 22 ccRCCs patients belonged to 3 prognostic sub-groups, i.e. those without disease recurrence, with recurrence and with metastatic disease at diagnosis. Thirty-two consecutive samples (16 ccRCC/NRC pairs) were used for stem-loop PCR validation. Novel miRNAs were predicted using 2 distinct bioinformatic pipelines. In total, 463 known miRNAs (expression frequency 1-150,000/million) were identified. We found that 100 miRNA were significantly differentially expressed between ccRCC and NRC. Differential expression of 5 miRNAs was confirmed by stem-loop PCR in the 32 ccRCC/NRC samples. With respect to RCC subgroups, 5 miRNAs discriminated between non-recurrent versus recurrent and metastatic disease, whereas 12 uniquely distinguished non-recurrent versus metastatic disease. Blocking overexpressed miR-210 or miR-27a in cell line SKCR-7 by transfecting specific antagomirs did not result in significant changes in proliferation or apoptosis. Twenty-three previously unknown miRNAs were predicted in silico. Quantitative genome-wide miRNA profiling accurately separated ccRCC from (benign) NRC. Individual differentially expressed miRNAs may potentially serve as diagnostic or prognostic markers or future therapeutic targets in ccRCC. The biological relevance of candidate novel miRNAs is unknown at present.

NOTCH1 signaling as a therapeutic target in Sézary syndrome.

NOTCH signaling is important for development and tissue homeostasis and is activated in many human cancers. We investigated a role for NOTCH1 signaling in Sézary syndrome (SS), a cutaneous T-cell lymphoma in which CD4+ tumor cells (Sézary cells) are present in the skin, lymph nodes, and peripheral blood. We show consistent expression of activated NOTCH1 by Sézary cells isolated from peripheral blood of SS patients, as well as the SS-derived cell lines SeAx and HuT78. In addition, immunohistochemical stainings of skin biopsies from SS patients showed consistent expression of nuclear NOTCH1 and its downstream target hairy/enhancer of split-1 (HES1) by Sézary cells. We demonstrate that this persistent NOTCH1 activation is not caused by mutations in the coding regions of NOTCH1 and F-box and WD40 domain protein 7 (FBWX7) genes. Inhibition of NOTCH1 signaling by gamma secretase inhibitors decreased cellular viability and induced apoptosis of Sézary cells. These observations argue that NOTCH1 signaling is functionally involved in the pathogenesis of SS, and inhibition of NOTCH1 signaling represents a new therapeutic target for the treatment of SS.