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To investigate the implementation of treat-to-target (T2T) and treatment satisfaction from Chinese rheumatologists' perspectives.This retrospective analysis of a cross-sectional database collected from rheumatologists and their adult patients with RA in China using Adelphi Real World Disease Specific Programme™ methodology. Multivariate logistic regression models were used to evaluate factors associated with T2T use, achievement of T2T goals, and physician treatment satisfaction.Sixty physicians provided data for 600 patients, of whom 39.0% (234/600) were being treated using T2T, and 64.9% (366/564) had achieved their T2T goal. Physicians were satisfied with treatment in 74.3% (445/599) of patients. Patients with a higher pain score were more likely to be managed using T2T (odds ratio (OR) 1.25; p = 0.017), but less likely to have achieved the T2T goal (OR 0.76; p = 0.004). T2T use was more likely if patients had a longer time since diagnosis ( 2 vs ≤ 2 years; OR 1.61; p = 0.031) or received targeted synthetic or biologic disease-modifying antirheumatic drugs (tsDMARDs or bDMARDs; OR 6.90; p 0.001). T2T goal achievement was more likely for patients with higher body mass index (≥ 24 vs 24 kg/mT2T implementation in China is suboptimal. Our findings provide insight into T2T implementation and physician treatment satisfaction, supporting T2T use in Chinese RA clinical practice. Key Points • T2T implementation in China is currently suboptimal. • Patients with greater pain were more likely to be managed using T2T but were less likely to have achieved their T2T goals. • Physician treatment satisfaction was associated with T2T goal achievement.

Brain capillaries are crucial for cognitive functions by supplying oxygen and other nutrients to and removing metabolic wastes from the brain. Recent studies have demonstrated that constriction of brain capillaries is triggered by beta-amyloid (Aβ) oligomers via endothelin-1 (ET1)-mediated action on the ET1 receptor A (ETRA), potentially exacerbating Aβ plaque deposition, the primary pathophysiology of Alzheimer’s disease (AD). However, direct evidence is still lacking whether changes in brain capillaries are causally involved in the pathophysiology of AD. Using APP/PS1 mouse model of AD (AD mice) relative to age-matched negative littermates, we identified that reductions of density and diameter of hippocampal capillaries occurred from 4 to 7 months old while Aβ plaque deposition and spatial memory deficit developed at 7 months old. Notably, the injection of ET1 into the hippocampus induced early Aβ plaque deposition at 5 months old in AD mice. Conversely, treatment of ferulic acid against the ETRA to counteract the ET1-mediated vasoconstriction for 30 days prevented reductions of density and diameter of hippocampal capillaries as well as ameliorated Aβ plaque deposition and spatial memory deficit at 7 months old in AD mice. Thus, these data suggest that reductions of density and diameter of hippocampal capillaries are crucial for initiating Aβ plaque deposition and spatial memory deficit at the early stages, implicating the development of new therapies for halting or curing memory decline in AD. Supplementary Information The online version contains supplementary material available at 10.1007/s13311-021-01024-7.

Excessive accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER) can trigger ER stress. Although regulation of this stress response in plants is an important and effective means of mitigating the damage caused by stress, the associated genes and mechanisms in maize remain largely unknown. In this study, we identified the ER stress-responsive gene ZmNF-YC13, which encodes a protein localized in the nuclei and cytoplasm of maize cells. The overexpression of ZmNF-YC13 in maize and Arabidopsis was found to confer plant ER stress tolerance, and gene expression analyses revealed that the overexpression of this gene upregulates the expression of genes involved in protein folding and the ER-associated degradation (ERAD) system, including ERdj, BiP, and E3 ubiquitin ligase. Moreover, we established that ZmNF-YC13 activates the promoters of the chaperone genes ZmERdj and ZmBiP in protoplasts, which function in the elimination of unfolded and misfolded proteins in the ER. Based on our findings, we propose that ZmNF-YC13 positively regulates the ER stress response in maize by controlling chaperone genes, and we believe that these results could provide valuable information for further maize resistance breeding.

Objective The purpose of this study was to explore the role of different undifferentiated components in the lymph node metastasis (LNM) of early mixed gastric cancer. Methods A total of 1596 patients with EGC who underwent gastrectomy were divided into four types: pure differentiated (PD), pure poorly differentiated (Poorly D), pure signet ring cell carcinoma (SRC), and mixed. Mixed type was classified into four subtypes: differentiated-predominant type mixed with poorly differentiated component (MD-P), poorly differentiated-predominant type mixed with differentiated component (MP-D), differentiated-predominant type mixed with SRC component (MD-S), and poorly differentiated-predominant type mixed with SRC component (MP-S). We analyzed the clinicopathological differences between all types and the rates of LNM of patients fulfilling endoscopic submucosal dissection (ESD) criteria. Results LNM was more common in mixed (21.9%) than in PD (7.5%, P P P = 0.003). LNM in MD-S (7.4%, P = 1.000) was not higher than in PD. MP-S (24.5%) showed a higher rate of LNM than SRC (11.3%, P P = 0.681). For lesions satisfying ESD criteria, MD-S (0%, P = 1.000), and MD-P (5.9%, P = 0.12) did not have higher rates of LNM than PD (1.4%). Conclusion The presence of poorly differentiated component but not SRC increases the LNM rate of mixed type. ESD is recommended for the treatment of MD-S and MD-P consistent with ESD criteria.

Salt-tolerant variety Chuanqiao No. 1 and salt-sensitive variety Chuanqiao No. 2 of Tartary buckwheat were used as experimental materials. The effect of aspartic acid on seed germination, physiological characteristics of seedlings and gene expression of salt exclusion in Tartary buckwheat were studied under NaCl stress of 150 mM. The results showed that the aspartic acid treatment could restore the seed germination rate and root vigor of seedlings to the control with non-damage level in salt-tolerant Tartary buckwheat variety under salt stress, and the salt-sensitive variety was increased greatly. Spraying aspartic acid had some protective effects on cell membrane of leaves in Tartary buckwheat under salt stress, and the protective effects were more obviously on salt-sensitive variety, and that could restore the activity of SOD and CAT of leaves to the control level in salt-tolerant Tartary buckwheat variety under salt stress, and the activity of antioxidant enzymes in salt-sensitive variety was increased significantly. The relative expression of FtNHX1 and FtSOS1 genes was increased significantly under salt stress, and that of FtNHX1 gene in salt-tolerant and salt-sensitive varieties was reached the maximum expression level at 12 h and 24 h respectively, while that of FtSOS1 gene in salt-tolerant and salt-sensitive varieties was reached the maximum expression level at 12 h, and the salt-tolerant variety was increased greatly. After spraying aspartic acid, the relative expression of FtNHX1 and FtSOS1 genes was increased more obviously. The relative expression of FtNHX1 gene in salt-tolerant and salt-sensitive varieties was reached the maximum expression level at 12 h, while that of FtSOS1 gene was reached the maximum expression level at 12 h and 24 h respectively, and that in salt-tolerant variety was increased especially more, indicating that spraying aspartic acid on gene expression of salt exclusion in salt-tolerant variety of Tartary buckwheat has a better effect under salt stress.

Background Circulating fibrocytes (CFs) have been shown to participate in subepithelial fibrosis of asthma with chronic airflow limitation by acting as an important source of fibroblasts deposited beneath airway epithelia. Serum amyloid P (SAP) is an innate inhibitor of fibrocytes differentiation. Store-operated Ca 2+ entry (SOCE) is the major Ca 2+ influx of non-excitable cells. In this study, the role of SOCE in the regulation of fibrocytes differentiation and the effects of Th2 cytokine IL-4 and SAP on SOCE of fibrocytes were investigated. Methods Peripheral blood mononuclear cells or monocytes were cultured in serum-free medium for 7 days to differentiate into fibrocytes; the expression of SOC channels was determined with PCR, SOCE was measured with Ca 2+ fluorescence imaging. Results IL-4 significantly promoted monocyte derived fibrocytes differentiation in vitro . It also increased both SOCE which was induced by thapsigargin or UTP and molecules STIM1 and Orai1 which were related to expression of SOC channels in fibrocytes. Fibrocytes differentiation induced by IL-4 and SOC channels activity could be inhibited by SOC channel blocker SKF-96365. As expected, SAP significantly inhibited IL-4-induced differentiation of fibrocytes, the activity of SOCE and the expression of STIM1 and Orai1 in IL-4-treated fibrocytes. Conclusion IL-4 and SAP reversely regulates cultured fibrocytes differentiation in vitro by respectively promoting or inhibiting the expression and activity of SOC channels in fibrocytes.

A fluorescent probe, with simplicity of structure and convenience of synthesis, is capable of detecting cysteine over other biothiols, such as homocysteine and glutathione. The detection limit of 60 nM and 190-fold increase in fluorescence intensity offer advantage for detection of Cys in biological systems. Furthermore, the probe 1 could be applied in bioimaging. We designed and synthesized the fluorescent probe 1, which displayed a highly selective and sensitive response to Cys over Hcy/GSH. The detection limit of 60 nM and 190-fold increase in fluorescence intensity offer advantage for detection of Cys in biological systems. Furthermore, the probe 1 could be applied in bioimaging.

The correct folding of proteins in the endoplasmic reticulum (ER) is vital for plant adaptation to adverse environmental conditions. The genes related to the ER stress response in maize are far from clear. In this study, a maize nuclear factor, NF-YC14, was identified in the regulation of the ER stress response. Overexpression of NF-YC14 improves plant ER stress tolerance and up-regulates the expression of downstream ER stress response genes. Moreover, NF-YC14 involves abscisic acid (ABA) signaling and overexpression of NF-YC14 confers plant hypersensitivity to ABA. Furthermore, overexpression of NF-YC14 enhances the expression of downstream ER stress response genes mediated by the ABA signaling pathway in Arabidopsis. These results indicate that NF-YC14 and ABA signaling regulate the expression of ER stress response genes and NF-YC14 links ER stress response to ABA signaling.

The silver sillago, Sillago sihama Forsskal is naturally distributed in Indo–West Pacific: Red Sea and Knysna, South Africa to Japan and south to Australia (Wantiez 1993), and is common along beaches, sandbars, mangrove creeks and estuaries. Adults bury themselves in the sand when disturbed (McKay 1992), and feed mainly on polychaete worms, small prawns (Penaeus), shrimps and amphipods (Allen et al. 2002). This fish is found in all Chinese waters including East China Sea, Yellow Sea, Bohai Sea, South China Sea, and the Northern Bay. In China, it is a common marine food fish species, and the supply of this fish relies on capture from the wild. So far, studies of this species have focussed on ecology (Lee et al. 1981; Lu et al. 2008), morphology of early development (Wan 1996), discrimination of the genus Sillago with sagittal otolith shape (Pan and Gao 2010), and phylogenetic relationships of the genus Sillago (Xue et al. 2010; Gao et al. 2011). In the present study, we developed 66 microsatellite loci isolated from a dinucleotide-enriched genomic library of S. sihama using the fast isolation by AFLP of sequences containing repeats (FIASCO) protocol of Zane et al. (2002). These markers should provide a tool for assessing genetic diversity and population structure of wild stocks.

We report for the first time, to our knowledge, the diode-pumped continuous-wave (CW) thin-disk Yb3+-doped Lu2O3 (Yb:LO) laser at 1 034 nm and the second-harmonic generation at 517 nm. With a 6.3% output coupler, the maximum output power is 1.17 W under a pump power of 18.5 W. Moreover, the intracavity second-harmonic generation (SHG) is also achieved with power of 193 mW at 517 nm by using an LiB3O5 (LBO) nonlinear crystal. The beam quality factor M2 is about 1.28. The fluctuation of the output power is about 3% in 1 h.

Aim: To study the caspase-3-independent mechanisms in oridonin-induced MCF-7 human breast cancer cell apoptosis in vitro . Methods: The viability of oridonin-treated MCF-7 cells was measured by MTT (thiazole blue) assay. Apoptotic cells with condensed nuclei were visualized by phase contrast microscopy. Nucleosomal DNA fragmentation was assayed by agarose gel electrophoresis. The apoptotic ratio was determined by lactate dehydrogenase assay. Cell cycle alternation and mitochondrial membrane potential were measured by flow cytometric analysis. Bax, Bcl-2, caspase-3, caspase-9, heat shock protein (Hsp)90, p53, p-p53, p21, Poly (ADP-ribose) polymerase (PARP), and the inhibitor of caspase-activated DNase (ICAD) protein expressions were detected by Western blot analysis. Results: Oridonin inhibited cell growth in a time- and dose-dependent manner. Cell cycle was altered through the upregulation of p53 and p21 protein expressions. Pancaspase inhibitor Z-VAD-fmk and calpain inhibitor II both decreased cell death ratio. Nucleosomal DNA fragmentation and the downregulation of Δψmit were detected in oridonin-induced MCF-7 cell apoptosis, which was involved in a postmitochondrial caspase-9-dependent pathway. Decreased Bcl-2 and Hsp90 expression levels and increased Bax and p21 expression levels were positively correlated with elevated levels of phosphorylated p53 phosphorylation. Moreover, PARP was partially cleaved by calpain rather than by capase-3. Conclusion: DNA damage provoked alternations in the mitochondrial and caspase-9 pathways as well as p53-mediated cell cycle arrest, but was not related to caspase-3 activity in oridonin-induced MCF-7 cells.

The inclusion compound built of tetra-n-butylammonium bromide-thiourea (1/2), [(n-C 4 H 9 ) 4 N + Br - .2(NH 2 ) 2 CS], has been prepared and characterized by X-ray crystallography. The compound crystalline in orthorhombic space group Pbca, with a = 16.872(6) A, b = 17.214(6) A, c = 18.561(6) A, V = 5390(3) A 3 , Z = 8. The compound features a sandwich-like crystal structure built up from planar layers. In the crystal structure, zigzag hydrogen-bonded thiourea ribbons are linked by bromide anions to generate puckered layers matching the (100) planes, and the (n-C 4 H 9 ) 4 N + cations occupy the intervening space.

Crystal structure of C41H53O7Br has been determined by single-crystal X-ray diffraction. The compound crystalline in the orthorhombic space group P212121, with a = 11.264(2), b = 12.058(2), c = 29.337(6) A, Z = 4. The bond angles of cyclopropane moiety in the molecule are approximate to 60° and agree with theoretic values of the internal angles in a cyclopropane, and two chiral menthyloxy groups are located above and under the whole chiral molecule, respectively. The configuration of the pentacyclic lactone is shown as envelope form.