OBJECTIVE: The current treatment and mechanism of Sjogren\'s syndrome (SS) are unclear. The purpose of the present study was to potential molecular mechanisms of SS.
METHODS: Immunohistochemical and immunofluorescence techniques reveal the targets and therapeutic approaches of SS.
RESULTS: We found through molecular biology techniques such as immunoblotting and immunoprecipitation that USP5 is a novel regulator of NLRP3 involvement in the pathological process of SS. USP5 was significantly downregulated in submandibular gland tissue of SS. Meanwhile, it was found that USP5 is a negative regulator of NLRP3 via ubiquitination NLRP3. In addition, SalvianolicacidB (SaB), a natural USP5 agonist, can alleviate ss by regulating the USP5/NLRP3 signaling pathway.
CONCLUSIONS: Therefore, this study provides a new mechanism for SS and also provides new therapeutic targets for treating SS.

The environmentally sustainable treatment of steel slag (SS) and oil shale waste (OSW) is a significant concern in the field of industrial development. The mining industry also faces challenges related to the high costs and carbon emissions associated with ordinary Portland cement (OPC), leading to environmental pollution. To address these challenges, this study aimed to develop a cost-effective and environmentally friendly binder for cemented paste backfill (CPB) by utilizing SS and calcined oil shale waste (COSW) as primary precursors. Extensive investigations were conducted to evaluate the properties of the CPB sample with varying COSW content, including rheological properties, mechanical strength, and microstructure. The binder sample was comprehensively characterized using isothermal calorimetric analysis, X-ray diffraction (XRD), thermogravimetry (TG), and scanning electron microscopy (SEM). Based on systematic experimentation, an optimal blend ratio for the binder was determined, consisting of 60 wt% SS, 15 wt% COSW, 15 wt% phosphogypsum (PG), and 10 wt% OPC. The exceptional performance of the binder was attributed to the substantial formation of precipitated ettringite (AFt), resulting in a more compact structure and improved mechanical strength. Additionally, a sequential extraction test revealed that the heavy metals in the CPB sample were mainly present in the residual fraction, demonstrating the effective immobilization of heavy metals by the binder.

Sjögren\'s syndrome (SS) is the second most common autoimmune rheumatism. Huoxue Jiedu Recipe (HXJDR) is a kind of traditional Chinese medicine with a variety of pharmacological functions; however, its biological function in SS has not been studied yet. Peripheral blood mononuclear cells (PBMCs) and serum samples were isolated from healthy controls and patients with SS. NOD/Ltj mice were used for developing the SS mouse model. The levels of inflammatory cytokines and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-related markers as well as dynamin-related protein 1 (Drp1) were determined by ELISA, quantitative real-time PCR, and western blot analysis, respectively. Hematoxylin and eosin and TUNEL staining detected the pathological damage. A transmission electron microscope was used to observe the mitochondrial microstructure. Inflammatory cytokines IL-18, IL-1β, B-cell activating factor (BAFF), BAFF-receptor (BAFF-R), IL-6, and TNF-α in serum samples and NLRP3 inflammasome-related makers (NLRP3, cysteinyl aspartate-specific proteinase 1 [caspase-1], apoptosis-associated speck-like protein containing a caspase-1 recruitment domain [ASC], IL-1β) in PBMCs were greatly upregulated in patients with SS. Furthermore, cytoplasmic phosphorylation of Drp1 and mitochondrial Drp1 level were significantly increased in PBMCs, while mitochondrial swelling and fuzzy inner ridge were observed in PBMCs of patients with SS, suggesting increased mitochondrial fission. Compared with control mice, SS mice showed decreased salivary flow rate, increased submandibular gland index, and more severe inflammatory infiltration and damage as well as mitochondrial fission in submandibular gland tissues. After HXJDR administration, these effects were significantly reversed. HXJDR treatment could alleviate the inflammatory infiltration and pathological damage in submandibular glands of SS mice by inhibiting Drp-1-dependent mitochondrial fission.

Great advancements have been made in understanding the pathogenesis of SS, but there remain unmet needs for effective and targeted treatments. Glandular and extraglandular dysfunction in SS is associated with autoimmune lymphocytic infiltration that invades the epithelial structures of affected organs. Regulatory T (Treg) cells are a subset of CD4+ T lymphocytes that maintain self-tolerance during physiological conditions. Besides inhibiting excessive inflammation and autoimmune response by targeting various immune cell subsets and tissues, Treg cells have also been shown to promote tissue repair and regeneration in pathogenic milieus. The changes of quantity and function of Treg cells in various autoimmune and chronic inflammatory disorders have been reported, owing to their effects on immune regulation. Here we summarize the recent findings from murine models and clinical data about the dysfunction of Treg cells in SS pathogenesis and discuss the therapeutic strategies of direct or indirect targeting of Treg cells in SS. Understanding the current knowledge of Treg cells in the development of SS will be important to elucidate disease pathogenesis and may guide research for successful therapeutic intervention in this disease.

When trains pass through damaged switch rails, rail head damage will change wheel-rail contact states from rolling frictions to unsteady contacts, which will result in impact vibrations and threaten structural safeties. In addition, under approaching and moving away rolling contact excitations and complex wheel-rail contacts, the non-stationary vibrations make it difficult to extract and analyze impact vibrations. In view of the above problems, this paper proposes a variational-mode-decomposition (VMD)-spectral-subtraction (SS)-based impact vibration extraction method. Firstly, the time domain feature analysis method is applied to calculate the time moments that the wheels pass joints, and to correct vehicle velocities. This can help estimate and confine impact vibration distribution ranges. Then, the stationary intrinsic mode function (IMF) components of the impact vibration are decomposed and analyzed with the VMD method. Finally, impact vibrations are further filtered with the SS method. For rail head damage with different dimensions, under different velocity experiments, the frequency and amplitude features of the impact vibrations are analyzed. Experimental results show that, in low-velocity scenarios, the proposed VMD-SS-based method can extract impact vibrations, the frequency features are mainly concentrated in 3500-5000 Hz, and the frequency and peak-to-peak features increase with the increase in excitation velocities.

Whether naive CD4+ T cells are dysregulated and associated with the overactivation of CD4+ T cells in primary SS (pSS) remains unclear. We aimed to explore the role and underlying mechanism of naive CD4+ T cells in pSS.
We examined the activation, proliferation and differentiation of naive CD4+ T cells from pSS patients and healthy controls. Differentially expressed genes were identified using RNA sequencing, and were overexpressed or silenced to determine the gene regulating follicular helper T (Tfh) cells. Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) with chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) was performed to explore the epigenetic mechanism. Naive CD4+ T cells were treated with pSS-related cytokines to explore the upstream signalling pathway.
pSS naive CD4+ T cells had higher potentials of activation, proliferation and differentiation towards Tfh cells. Thymocyte selection-associated high mobility group box protein (TOX) was upregulated in pSS naive CD4+ T cells and promoted T cell activation and Tfh cell polarization. TOX silencing in pSS naive CD4+ T cells downregulated B cell lymphoma 6 (BCL6) expression and altered levels of multiple Tfh-associated genes. ChIP-seq analysis implied that TOX bound to the BCL6 locus, where there were accessible regions found by ATAC-seq. IFN-α induced TOX overexpression, which was attenuated by Janus kinase (JAK) and signal transducer and activator of transcription 1 (STAT1) inhibitors.
Our data suggest that TOX in pSS naive CD4+ T cells is upregulated, which facilitates Tfh cell differentiation. Mechanistically, IFN-α induces TOX overexpression in naive CD4+ T cells through JAK-STAT1 signalling and TOX regulates BCL6 expression. Therefore, IFN-α-JAK-STAT1 signalling and TOX might be potential therapeutic targets in pSS.

Low blood fluid shear stress (SS) promotes vascular remodeling and atherosclerosis; however, the effects of high (H)SS on vascular remodeling and atherogenesis is not fully clarified. The major goal of this study was to investigate the role of HSS in atherosclerotic plaque formation. A perivascular SS modifier was implanted in the right carotid artery of apolipoprotein E (ApoE)‑/‑ mice to induce HSS, whereas the left carotid artery represented undisturbed (U)SS as a control in vivo. In vitro modeling used human umbilical vein endothelial cells and vascular smooth muscle cells exposed to HSS (2.5 Pa) using a parallel‑plate flow system. The results demonstrated that there were no plaque formations or endothelial cells in the HSS regions of the carotid artery in ApoE‑/‑ mice. The number of umbilical vein endothelial cells was markedly decreased in a time‑dependent manner in HSS. HSS significantly decreased α‑smooth muscle actin and increased osteopontin protein expression levels compared with USS in vascular smooth muscle cells (P<0.05). In addition, HSS significantly increased the protein expression levels of collagen α1(XVIII) chain/endostatin and matrix metalloproteinase‑8 in vascular smooth muscle cells. These data indicated that HSS may prevent atherosclerotic plaque formation through endothelium denudation and contractile‑to‑synthetic phenotypic conversion of smooth muscle cells.

The glutamic acid decarboxylase 65 antibody (GAD65-Ab) is an autoimmune marker in some diseases such as diabetes or autoimmune disorders of the central nervous system such as stiff-man syndrome. It can appear with other pancreatic autoantibodies, such as insulin autoantibodies (IAA), presenting as early signs of pancreatic islet β-cells impairing, and play roles in the pathogenesis of type1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA). Positive GAD65-Ab is rarely observed in insulin-dependent diabetic patients with other acquired autoimmune diseases, such as Sjogren\'s syndrome (SS). Besides, LADA revealed by islet autoantibodies such as GAD65-Ab can also be complicated with Hashimoto\'s thyroiditis (HT), another autoimmune thyroid disease. To date, whether GAD65-Ab positive in patients with autoimmune diseases predicts the onset or progression to T1D or LADA remains unknown. Herein, two unique cases of middle-aged Chinese Han women free from diabetes for three years are described despite their blood tests persistently testing positive for GAD65-Ab or IAA. Both patients suffered from HT and SS. Follow-up OGTTs (oral glucose tolerance test) for three years revealed that the patients had a well-controlled glycemic level and normal pancreatic function. However, one of the patients had a temporary increase of postprandial glucose after a short-term loss of diet control. The presence of auto-immune antibodies in these patients had little impact on glucose tolerance or insulin secretion in 3 years. The study postulate that both the primary immune injury caused by serum GAD65-Ab positive, an autoimmune marker, and increased body weight contribute to the progression of LADA.

OBJECTIVE: Investigate the influence of benazepril and amlodipine on the expression of secretin (PZ) and somatostatin (SS) in spontaneously hypertensive rats (SHR).
METHODS: Forty-five SHRs (14 weeks old, male) were randomly assigned into 3 groups (n=15):SHR group, Benazepril group (which was given benazepril 0.90 mg·kg-1·d-1) and Amlodipine group (SHRs were given amlodipine 0.45 mg· kg-1·d-1), taking WistarKyoto(WKY) as normal control (n=15), meanwhile, rats in SHR group and WKY group were given the same volume of distilled water. After 8 weeks of intervention, the expression of protein and mRNA of PZ in duodenum and SS in sinuses ventriculi was detected by enzyme-linked immunoassay and RT-PCR.
RESULTS: After 8 weeks of intervention, compared with the WKY group, the expression of protein and mRNA of PZ in duodenum and SS in sinuses ventriculi was increased significantly in SHR group (P<0. 05). Compared with SHR group, the expression of PZ in duodenum and SS in sinuses ventriculi was decreased significantly in Benazepril group and Amlodipine group (P<0.05). Compared with Benazepril group, in Amlodipine group the expression of PZ mRNA in duodenum and SS mRNA in sinuses ventriculi was decreased more significantly (P<0.05).
CONCLUSIONS: The regulation disorder of PZ in duodenum and SS in sinuses ventriculi exists in SHR. The antihypertensive effect of benazepril and amlodipine may be realized by regulating the expression of PZ and SS, while the regulation of amlodipine is more obvious than benazepril.

Chlorophyll content, one of the most important physiological parameters related to plant photosynthesis, is usually used to predict yield potential. To map the quantitative trait loci (QTLs) underlying the chlorophyll content of rice leaves, a double haploid (DH) population was developed from an indica/japonica (Zhenshan 97/Wuyujing 2) crossing and two backcross populations were established subsequently by backcrossing DH lines with each of their parents. The contents of chlorophyll a and chlorophyll b were determined by using a spectrophotometer to directly measure the leaf chlorophyll extracts. To determine the leaf chlorophyll retention along with maturation, all measurements were performed on the day of heading and were repeated 30 days later. A total of 60 QTLs were resolved for all the traits using these three populations. These QTLs were distributed on 10 rice chromosomes, except chromosomes 5 and 10; the closer the traits, the more clustering of the QTLs residing on common rice chromosomal regions. In general, the majority of QTLs that specify chlorophyll a content also play a role in determining chlorophyll b content. Strangely, chlorophyll content in this study was found mostly to be lacking or to have a negative correlation with yield. In both backcross F1 populations, overdominant (or underdominant) loci were more important than complete or partially dominant loci for main-effect QTLs and epistatic QTLs, thereby supporting previous findings that overdominant effects are the primary genetic basis for depression in inbreeding and heterosis in rice.