Rheumatoid arthritis (RA) is a heterogeneous autoimmune disorder that leads to severe joint deformities, negatively affecting the patient's quality of life. Extracellular vesicles (EVs), which include exosomes and ectosomes, act as intercellular communication mediators in several physiological and pathological processes in various diseases including RA. In contrast, EVs secreted by mesenchymal stem cells perform an immunomodulatory function and stimulate cartilage repair, showing promising therapeutic results in animal models of RA. EVs from other sources, including dendritic cells, neutrophils and myeloid-derived suppressor cells, also influence the biological function of immune and joint cells. This review describes the role of EVs in the pathogenesis of RA and presents evidence supporting future studies on the therapeutic potential of EVs from different sources. This information will contribute to a better understanding of RA development, as well as a starting point for exploring cell-free-based therapies for RA.

Precision and accuracy of quantitative scanning transmission electron microscopy (STEM) methods such as ptychography, and the mapping of electric, magnetic, and strain fields depend on the dose. Reasonable acquisition time requires high beam current and the ability to quantitatively detect both large and minute changes in signal. A new hybrid pixel array detector (PAD), the second-generation Electron Microscope Pixel Array Detector (EMPAD-G2), addresses this challenge by advancing the technology of a previous generation PAD, the EMPAD. The EMPAD-G2 images continuously at a frame-rates up to 10 kHz with a dynamic range that spans from low-noise detection of single electrons to electron beam currents exceeding 180 pA per pixel, even at electron energies of 300 keV. The EMPAD-G2 enables rapid collection of high-quality STEM data that simultaneously contain full diffraction information from unsaturated bright-field disks to usable Kikuchi bands and higher-order Laue zones. Test results from 80 to 300 keV are presented, as are first experimental results demonstrating ptychographic reconstructions, strain and polarization maps. We introduce a new information metric, the maximum usable imaging speed (MUIS), to identify when a detector becomes electron-starved, saturated or its pixel count is mismatched with the beam current.

We present an experimental study of the large-scale vortex (or large-scale circulation, LSC) in turbulent Rayleigh–Bénard convection in a $\varGamma =\text {diameter}/\text {height}=2$ cylindrical cell. The working fluid is deionized water with Prandtl number ($Pr$) around 5.7, and the Rayleigh number ($Ra$) ranges from $7.64\times 10^7$ to $6.06\times 10^8$. We measured the velocity field in various vertical cross-sectional planes by using the planar particle image velocimetry technique. The velocity measurement in the LSC central plane shows that the flow is in the single-roll form, and the centre of the single-roll (vortex) does not always stay at the centre of the cell; instead, it orbits periodically in the direction opposite to the flow direction of the LSC, with its trajectory in the shape of an ellipse. The velocity measurements in the three vertical planes in parallel to the LSC central plane indicate that the flow is in the vortex tube form horizontally filling almost the whole cell, and the centre line of the vortex tube is consistent with the so-called ‘jump rope’ form proposed by a previous study that combined numerical simulation and local velocity measurements in the low $Pr$ case (Vogt et al., Proc. Natl Acad. Sci. USA, vol. 115, 2018, pp. 12674–12679). In addition, we found that the oscillation of the local velocity in $\varGamma =2$ cells originates from the periodical orbiting of the vortex centre. Our velocity measurements further indicate that the vortex centre orbiting is absent in $\varGamma =1$ cells, at least in the $Ra$ range of our experiments.

Pyroptosis is a recently identified mechanism of programmed cell death related to Caspase-1 that triggers a series of inflammatory reactions by releasing several proinflammatory factors such as IL-1β and IL-18. The process is characterised by the rupture of cell membranes and the release of cell contents through the mediation of gasdermin (GSDM) proteins. GSDMD is an important member of the GSDM family and plays a critical role in the two pathways of pyroptosis. Diabetic nephropathy (DN) is a microvascular complication of diabetes and a major cause of end-stage renal disease. Recently, it was revealed that GSDMD-mediated pyroptosis plays an important role in the occurrence and development of DN. In this review, we focus on two types of kidney cells, tubular epithelial cells and renal podocytes, to illustrate the mechanism of pyroptosis in DN and provide new ideas for the prevention, early diagnosis and molecular therapy of DN.

The southeastern Central Asian Orogenic Belt (CAOB) records the assembly process between several micro-continental blocks and the North China Craton (NCC), with the consumption of the Paleo-Asian Ocean (PAO), but whether the S-wards subduction of the PAO beneath the northern NCC was ongoing during Carboniferous–Permian time is still being debated. A key issue to resolve this controversy is whether the Carboniferous magmatism in the northern NCC was continental arc magmatism. The Alxa Block is the western segment of the northern NCC and contiguous to the southeastern CAOB, and their Carboniferous–Permian magmatism could have occurred in similar tectonic settings. In this contribution, new zircon U–Pb ages, elemental geochemistry and Sr–Nd isotopic analyses are presented for three early Carboniferous granitic plutons in the southwestern Alxa Block. Two newly identified aluminous A-type granites, an alkali-feldspar granite (331.6 ± 1.6 Ma) and a monzogranite (331.8 ± 1.7 Ma), exhibit juvenile and radiogenic Sr–Nd isotopic features, respectively. Although a granodiorite (326.2 ± 6.6 Ma) is characterized by high Sr/Y ratios (97.4–139.9), which is generally treated as an adikitic feature, this sample has highly radiogenic Sr–Nd isotopes and displays significantly higher K2O/Na2O ratios than typical adakites. These three granites were probably derived from the partial melting of Precambrian continental crustal sources heated by upwelling asthenosphere in lithospheric extensional setting. Regionally, both the Alxa Block and the southeastern CAOB are characterized by the formation of early Carboniferous extension-related magmatic rocks but lack coeval sedimentary deposits, suggesting a uniform lithospheric extensional setting rather than a simple continental arc.

Although many organizations encourage employees to voice, employees may be reluctant to voice directly because they are afraid that their supervisors will perceive it as challenging their face (i.e., the positive image or social value of an individual). Alternatively, employees could deliver improvements or express concerns to their supervisors using indirect and implicit approaches, which we refer to as ‘implicit voice delivery’. Applying face theory, we examine the antecedents and outcomes as well as two boundary conditions of implicit voice delivery in organizations with two studies. In Study 1, we define the construct and develop a measure of implicit voice delivery. In Study 2, we test our proposed model with supervisor-subordinate dyadic data from a time-lagged survey. Results demonstrate that concern for other people's face drives employees to express their voices implicitly and that this relationship is stronger when supervisors’ concern for their own face is high rather than low. In addition, implicit voice delivery is associated with supervisors’ favorable response in terms of voice endorsement. Furthermore, the effect on voice endorsement is stronger when the supervisor is more able to infer meaning from implicit messages. Theoretical contribution and managerial implications are discussed.

The Rhynchonellida is a major group of brachiopods that survived the “big five” mass extinctions and flourished after the Permian/Triassic (P/Tr) crisis. However, phylogenetic and character evolution in the Rhynchonellida across the P/Tr transition is poorly understood. In view of the widespread homoplasy across this order, we employ a tip-dated Bayesian analysis to reconstruct phylogenetic relationships for late Permian–Triassic rhynchonellides. The same data were also analyzed using three other methods: undated Bayesian, equal-weighting, and implied-weighting parsimony. Compared with trees generated by other methods, those constructed by tip-dating best account for the homoplasy in this group and are closer to previous assumptions on the evolution of this order. Based on the analyses of multiple trees, the major increase in lineage richness occurred in the Early and early Middle Triassic. Also, richness in the Anisian almost reached the highest level seen in the Triassic. According to fossil records, a pronounced reduction in shell size and in the development of ornamentation occurred after the P/Tr extinction, which is largely due to the loss of large and highly sculptured genera and the diversification of small-sized and weakly ornamented genera. Ancestral-state estimation of shell size and development of ornamentation, coupled with comparisons of other characters, indicate that the Early–Middle Triassic mature “small-sized taxa” may have characters displayed by juveniles of their ancestors. This suggests that for these genera, paedomorphosis was possibly a strategy to survive and diversify in the harsh environment after the P/Tr extinction.

Household entrepreneurship is a basic unit of entrepreneurial activity, and a crucial aspect of connecting personal and social wellbeing. This study examines the relationship between the proportion of elderly family members and household entrepreneurship. This study also assesses the mediating effect of the middle-aged generation's support to their parents and the moderating effect of the parents’ support with respect to the proportion of elderly family members and entrepreneurship. We use data from the China Family Panel Studies. We adopt the instrumental variable method to deal with endogeneity, robustness and credibility of the estimation results. The results show that a higher proportion of elderly family members impedes household entrepreneurship. Moreover, the financial and instrumental support provided by the middle-aged generation to their parents significantly mediates the relationship between the proportion of elderly family members and household entrepreneurship. In turn, parents’ financial support to the middle-aged generation moderates the focal relationship; however, parents’ instrumental support does not moderate the focal relationship. These findings emphasise the need to develop a comprehensive social security network for older adults that will indirectly promote household entrepreneurship, and improve personal and social wellbeing.

DNA methylation is one of the most important epigenetic modifications in breast cancer (BC) development, and long-term dietary habits can alter DNA methylation. Cadherin-4 (CDH4, a member of the cadherin family) encodes Ca2+-dependent cell–cell adhesion glycoproteins. We conducted a case–control study (380 newly diagnosed BC and 439 cancer-free controls) to explore the relationship of CDH4 methylation in peripheral blood leukocyte DNA (PBL DNA), as well as its combined and interactive effects with dietary factors on BC risk. A case-only study (335 newly diagnosed BC) was conducted to analyse the association between CDH4 methylation in breast tissue DNA and dietary factors. CDH4 methylation was detected using quantitative methylation-specific PCR. Unconditional logistic regressions were used to analyse the association of CDH4 methylation in PBL DNA and BC risk. Cross-over analysis and unconditional logistic regression were used to calculate the combined and interactive effects between CDH4 methylation in PBL DNA and dietary factors in BC. CDH4 hypermethylation was significantly associated with increased BC risk in PBL DNA (ORadjusted (ORadj) = 2·70, (95 % CI 1·90, 3·83), P < 0·001). CDH4 hypermethylation also showed significant combined effects with the consumption of vegetables (ORadj = 4·33, (95 % CI 2·63, 7·10)), allium vegetables (ORadj = 7·00, (95 % CI 4·17, 11·77)), fish (ORadj = 7·92, (95 % CI 3·79, 16·53)), milk (ORadj = 6·30, (95 % CI 3·41, 11·66)), overnight food (ORadj = 4·63, (95 % CI 2·69, 7·99)), pork (ORadj = 5·59, (95 % CI 2·94, 10·62)) and physical activity (ORadj = 4·72, (95 % CI 2·87, 7·76)). Moreover, consuming milk was significantly related with decreased risk of CDH4 methylation (OR = 0·61, (95 % CI 0·38, 0·99)) in breast tissue. Our findings may provide direct guidance on the dietary intake for specific methylated carriers to decrease their risk for developing BC.

The staining procedure is critical for investigating intra- and extra-cellular ultrastructure of microorganisms by transmission electron microscopy (TEM). Here, we propose a new ultra-low lead staining (ULLS) technique for preparing the ultrathin sections for TEM analysis. Sections of Enterobacter sp. (bacteria), Aspergillus niger (filamentous fungi), Rhodotorula mucilaginosa (fungi), and Chlamydomonas reinhardtii (microalgae) were tested. Compared with the sections prepared by the typical double-staining technique, ULLS-based sections showed evident advantages: (i) the staining process only required the addition of Pb(NO3)2; (ii) the Pb level during incubation was set as low as 1 mg/L, which had negligible toxicity to most microbial cells; (iii) the Pb cations were added during microbial culture, which avoided complicated sample preparation as in typical double staining. Taking C. reinhardtii as an example, the ULLS technique allowed fine investigation of microbial ultrastructure, e.g., starch granule, mitochondrion, Golgi apparatus, vacuole, and vesicle. Meanwhile, the physiological processes of the cells such as cell lysis and exocytosis were successfully captured, with relatively high contrast. This study hence shows a bright future on preparation of the high-quality ultrathin sections of microbial cells by the ULLS technique.

The interplay between sustainability and anthropogenic landscape transformation is crucial to understanding the past decline and eradication of wild animals. The Bronze Age site of Zaoshugounao is located in the Guanzhong region of China, an area critical in the formation and development of early Chinese civilisation. Drawing upon zooarchaeological, palaeoenvironmental and textual evidence, analysis of sika deer remains from Zaoshugounao reveals sustainable sika deer-hunting strategies at the site, despite an overall long-term trend in the sika deer population decline and habitat loss. The authors’ results highlight the complexity and diversity of human-sika relations and contribute to ongoing discussions surrounding wild animal eradication and conservation in China.

The prevalence of workplace deviance has become an urgent issue for managers. Although increasing research has investigated the detriments of workplace deviance on other employees and organizations, limited research has studied the harm of workplace deviance on perpetrators themselves. This research drew from appraisal theories of emotion and sought to understand perpetrators' affective and behavioral consequences of engaging in deviance. Using a diary method, a survey consisting of 92 employees with 918 observations was conducted. The results reveal that employees' deviance is positively related to their feeling of fear and that fear overrides feelings of guilt, ultimately decreasing work engagement and organizational citizenship behavior (OCB). Importantly, perceived benevolent leadership weakens the effects of deviance on perpetrators themselves by relieving fear associated with past deviance and mitigating the negative influences of fear on OCB.

Poor utilisation efficiency of carbohydrate always leads to metabolic phenotypes in fish. The intestinal microbiota plays an important role in carbohydrate degradation. Whether the intestinal bacteria could alleviate high-carbohydrate diet (HCD)-induced metabolic phenotypes in fish remains unknown. Here, a strain affiliated to Bacillus amyloliquefaciens was isolated from the intestine of Nile tilapia. A basal diet (CON), HCD or HCD supplemented with B. amy SS1 (HCB) was used to feed fish for 10 weeks. The beneficial effects of B. amy SS1 on weight gain and protein accumulation were observed. Fasting glucose and lipid deposition were decreased in the HCB group compared with the HCD group. High-throughput sequencing showed that the abundance of acetate-producing bacteria was increased in the HCB group relative to the HCD group. Gas chromatographic analysis indicated that the concentration of intestinal acetate was increased dramatically in the HCB group compared with that in the HCD group. Glucagon-like peptide-1 was also increased in the intestine and serum of the HCB group. Thus, fish were fed with HCD, HCD supplemented with sodium acetate at 900 mg/kg (HLA), 1800 mg/kg (HMA) or 3600 mg/kg (HHA) diet for 8 weeks, and the HMA and HHA groups mirrored the effects of B. amy SS1. This study revealed that B. amy SS1 could alleviate the metabolic phenotypes caused by HCD by enriching acetate-producing bacteria in fish intestines. Regulating the intestinal microbiota and their metabolites might represent a powerful strategy for fish nutrition modulation and health maintenance in future.

GBF1 [Golgi brefeldin A (BFA) resistance factor 1] is a member of the guanine nucleotide exchange factors Arf family. GBF1 localizes at the cis-Golgi and endoplasmic reticulum (ER)-Golgi intermediate compartment where it participates in ER-Golgi traffic by assisting in the recruitment of the coat protein COPI. However, the roles of GBF1 in oocyte meiotic maturation are still unknown. In the present study, we investigated the regulatory functions of GBF1 in mouse oocyte organelle dynamics. In our results, GBF1 was stably expressed during oocyte maturation, and GBF1 localized at the spindle periphery during metaphase I. Inhibiting GBF1 activity led to aberrant accumulation of the Golgi apparatus around the spindle. This may be due to the effects of GBF1 on the localization of GM130, as GBF1 co-localized with GM130 and inhibiting GBF1 induced condensation of GM130. Moreover, the loss of GBF1 activity affected the ER distribution and induced ER stress, as shown by increased GRP78 expression. Mitochondrial localization and functions were affected, as the mitochondrial membrane potential was altered. Taken together, these results suggest that GBF1 has wide-ranging effects on the distribution and functions of Golgi apparatus, ER, and mitochondria as well as normal polar body formation in mouse oocytes.

The impact of diet on the metabolic syndrome (MetS) and CVD has been investigated widely, but few studies have investigated the association between dietary patterns (DP) and the predicted CVD, derived from reduced rank regression (RRR). The objectives of this study were to derive DP using RRR and principal component analysis (PCA) and investigate their associations with the MetS and estimated 10-year atherosclerotic CVD (ASCVD). We used the baseline dataset from the Xinjiang multi-ethnic cohort study in China, collected from June 2018 to May 2019. A total of 14 982 subjects aged 35–74 years from Urumqi, Huo Cheng and Mo Yu were included in the analysis. The 10-year ASCVD risk was estimated using the Chinese ASCVD risk equations. The associations of DP with the MetS and 10-year ASCVD were determined using multivariable logistic regression models. In Urumqi and Mo Yu, the increased RRR DP score was associated with a higher OR of having the MetS and with a higher OR of elevated 10-year ASCVD risk. However, only the first DP determined by PCA in Urumqi was inversely associated with the MetS and elevated 10-year ASCVD risk. The prevalence of the MetS and elevated ASCVD risk in urban population is higher than that in rural areas. Our results may help nutritionists develop more targeted dietary strategies to prevent the MetS and ASCVD in different regions in China.