Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the synovial membrane, leading to cartilage destruction and bone erosion. Due to the complex pathogenesis of RA and the limitations of current therapies, increasing research attention has been directed towards novel strategies targeting fibroblast-like synoviocytes (FLS), which are key cellular components of the hyperplastic pannus. Recent studies have highlighted the pivotal role of FLS in the initiation and progression of RA, driven by their tumour-like transformation and the secretion of pro-inflammatory mediators, including cytokines, chemokines and matrix metalloproteinases. The aggressive phenotype of RA-FLS is marked by excessive proliferation, resistance to apoptosis, and enhanced migratory and invasive capacities. Consequently, FLS-targeted therapies represent a promising avenue for the development of next-generation RA treatments. The efficacy of such strategies – particularly those aimed at modulating FLS signalling pathways – has been demonstrated in both preclinical and clinical settings, underscoring their therapeutic potential. This review provides an updated overview of the pathogenic mechanisms and functional roles of FLS in RA, with a focus on critical signalling pathways under investigation, including Janus kinase/signal transducer and activator of transcription (JAK/STAT), mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB), Notch and interleukin-1 receptor-associated kinase 4 (IRAK4). In addition, we discuss the emerging understanding of FLS-subset-specific contributions to immunometabolism and explore how computational biology is shaping novel targeted therapeutic strategies. A deeper understanding of the molecular and functional heterogeneity of FLS may pave the way for more effective and precise therapeutic interventions in RA.

Remote center-of-motion (RCM) manipulators are a key issue in minimally invasive surgeries (MIS). The existing RCM parallel mechanisms (PMs) can only generate RCM motion based on the invariant RCM. To provide mobility for RCM, this paper designed a new family of RCM PMs with movable RCM that features a double-stage topological structure. Drawing mainly on configuration evolution and Lie-group, a general approach is proposed to design double-stage PMs with movable RCM. Feasible limbs for 2R1T RCM motion are enumerated and used to construct the secondary PM. Type synthesis of the primary PMs that realize movable RCM is accomplished based on the method presented. Different connection styles between the two stages that ensure the geometrical conditions of RCM motion are designed. Using different connection styles, double-stage PMs with movable RCM are constructed. These new RCM PMs can realize precise positioning of RCM by taking advantage of the primary PMs, which indicates their potential application prospects in MIS.

The resistance to fenoxaprop-P-ethyl, a herbicide that inhibits acetyl-CoA carboxylase (ACCase), has emerged in shortawn foxtail (Alopecurus aequalis Sobol.) since the 1990s, presenting a considerable challenge to wheat (Triticum aestivum L.) production in China. One of the primary mechanisms responsible for this high-level resistance is the presence of mutations at codons 1781, 2041, and 2078 in the ACCase gene. However, the conventional methods used to detect these mutations, such as polymerase chain reaction (PCR) and gene sequencing, are time-consuming and labor-intensive. To address this issue and enable the prompt and effective detection of these common ACCase mutations in A. aequalis, a loop-mediated isothermal amplification (LAMP) strategy was developed. The LAMP assay specifically targets the Ile-1781-Leu and Asp-2078-Gly mutations within the ACCase gene of A. aequalis. Through the optimization of primers, systems, and conditions, the LAMP assay enables rapid differentiation between wild-type individuals and mutants of A. aequalis carrying either of these two mutations. Including SYBR Green I dye in the final reaction mixtures enables detection of the target mutation through a noticeable color change that can be observed with the naked eye. It is noteworthy that the sensitivity of the LAMP assay was approximately 104-fold greater than that of conventional PCR methods. Additionally, a derived cleaved amplified polymorphic sequence (dCAPS) assay was established for each mutation to distinguish between homozygous and heterozygous mutants. Overall, the developed LAMP assay could efficiently detect the Ile-1781-Leu and Asp-2078-Gly mutations in the ACCase gene of A. aequalis, offering significant advantages for the monitoring and management of fenoxaprop-P-ethyl resistance.

The laboratory generation and diagnosis of uniform near-critical-density (NCD) plasmas play critical roles in various studies and applications, such as fusion science, high energy density physics, astrophysics as well as relativistic electron beam generation. Here we successfully generated the quasistatic NCD plasma sample by heating a low-density tri-cellulose acetate (TCA) foam with the high-power-laser-driven hohlraum radiation. The temperature of the hohlraum is determined to be 20 eV by analyzing the spectra obtained with the transmission grating spectrometer. The single-order diffraction grating was employed to eliminate the high-order disturbance. The temperature of the heated foam is determined to be T = 16.8 ± 1.1 eV by analyzing the high-resolution spectra obtained with a flat-field grating spectrometer. The electron density of the heated foam is about $N_e=4.0\pm 0.3\times {10}^{20}{\text{cm}}^{-3}$ under the reasonable assumption of constant mass density.

The role of Mn oxide in the abiotic formation of humic substances has been well demonstrated. However, information on the effect of crystal structure and surface-chemical characteristics of Mn oxide on this process is limited. In the present study, hexagonal and triclinic birnessites, synthesized in acidic and alkali media, were used to study the influence of the crystal-structure properties of birnessites on the oxidative polymerization of hydroquinone and to elucidate the catalytic mechanism of birnessites in the abiotic formation of humic-like polymers in hydroquinone-birnessite systems. The intermediate and final products formed in solution and solid-residue phases were identified by UV/Visible spectroscopy, atomic absorption spectrometry, Fourier-transform infrared spectroscopy, X-ray diffraction, solid-phase microextraction-gaschromatography-mas ss pectrometry, ion chromatography, and ultrafiltration. The degree of oxidative polymerization of hydroquinone wasenhanced with increase in the interlayer hydrated H+, the average oxidation state (AOS), and the specific surface area of birnessites. The nature of the functional groups of the humic-like polymers formed was, however, almost identical when hydroquinone was catalyzed by hexagonal and triclinic birnessites with similar AOS of Mn. The results indicated that crystal structure and surface-chemistry characteristics have significant influence on the oxidative activity of birnessites and the degree of polymerization of hydroquinone, but have little effect on the abiotic formation mechanism of humic-like polymers. The proposed oxidative polymerization pathway for hydroquinone isthat, asit approachesthe birnessite, it formsp recursor surface complexes. Asa strong oxidant, birnessite accepts an electron from hydroquinone, which is oxidized to 1,4-benzoquinone. The coupling, cleavage, polymerization, and decarboxylation reactionsaccompany the generation of 1,4-benzoquinone, lead to the release of CO2 and carboxylic acid fragments, the generation of rhodochrosite, and the ultimate formation of humic-like polymers. These findings are of fundamental significance in understanding the catalytic role of birnessite and the mechanism for the abiotic formation of humic substances in nature.

The formation of manganese (Mn) oxides is influenced by environmental conditions and, in some red soils, Mn oxides occur as coatings on the surface of kaolinite particles in the form of colloidal films or fine particles. The present study aimed to explore the types of formation mechanisms of Mn oxide minerals on the surface of kaolinite. Mn oxide minerals synthesized by reducing the Mn in KMnO4 with a divalent Mn salt (MnSO4) were examined using X-ray diffraction (XRD) and scanning electron microscopy (SEM). The effects of various initial molar ratios of Mn2+/Mn7+ (R = 1:0.67, 1:1, 1:2, and 1:4), cationic species (Na+ or Mg2+), synthesis temperatures (30, 60, and 110°C), and amount of added kaolinite (0.25, 0.5, 1.0, 2.0, and 5.0 g) on the formation of Mn oxides were studied. The results showed that Mn oxide mineral types were affected by the initial R value and the background cation. With decreases in the initial R value, the synthesized minerals transformed from cryptomelane to birnessite. The relative mass ratios of kaolinite to Mn oxide were calculated as 1:0.92, 1:0.63, 1:1.15, and 1:1.63. The sodium cation (Na+) had a greater role than Mg2+ in promoting the dissolution–recrystallization of birnessite to cryptomelane. The synthesis temperature had no effect on mineral types, but Mn content increased as temperature increased. When the amount of added kaolinite was increased from 0.25 to 5.0 g, Mn oxide minerals formed gradually and transformed from birnessite to cryptomelane. This work revealed a possible formation process and reaction mechanism on the surface of kaolinite particles in some red soils.

Machine vision has been extensively researched in the field of unmanned aerial vehicles (UAV) recently. However, the ability of Sense and Avoid (SAA) largely limited by environmental visibility, which brings hazards to flight safety in low illumination or nighttime conditions. In order to solve this critical problem, an approach of image enhancement is proposed in this paper to improve image qualities in low illumination conditions. Considering the complementarity of visible and infrared images, a visible and infrared image fusion method based on convolutional sparse representation (CSR) is a promising solution to improve the SAA ability of UAVs. Firstly, the source image is decomposed into a texture layer and structure layer since infrared images are good at characterising structural information, and visible images have richer texture information. Both the structure and the texture layers are transformed into the sparse convolutional domain through the CSR mechanism, and then CSR coefficient mapping are fused via activity level assessment. Finally, the image is synthesised through the reconstruction results of the fusion texture and structure layers. In the experimental simulation section, a series of visible and infrared registered images including aerial targets are adopted to evaluate the proposed algorithm. Experimental results demonstrates that the proposed method increases image qualities in low illumination conditions effectively and can enhance the object details, which has better performance than traditional methods.

Shortawn foxtail (Alopecurus aequalis Sobol.) is an obligate wetland plant that is widely distributed throughout Europe, temperate Asia, and North America. In China, it is widespread in the middle and lower reaches of the Yangtze River as a noxious weed in winter cropping fields with a rice (Oryza sativa L.) rotation. The acetolactate synthase (ALS)-inhibiting herbicide mesosulfuron-methyl has been widely used to control annual grass and broadleaf weeds, including A. aequalis, in wheat (Triticum aestivum L.) fields, leading to the selection of herbicide-resistant weeds. In this study, an A. aequalis population, AHFT-4, that survived mesosulfuron-methyl at the field-recommended rate (9 g ai ha−1) was collected in Anhui Province. Single-dose testing confirmed that the suspected resistant AHFT-4 had evolved resistance to mesosulfuron-methyl. Target gene sequencing revealed a resistance mutation of Pro-197-Ala in ALS1 of the resistant plants, and a derived cleaved amplified polymorphic sequence marker was developed to specifically detect the mutation. A relative expression assay showed no significant difference in ALS expression between AHFT-4 and a susceptible population without or with mesosulfuron-methyl treatment. Whole-plant dose–response bioassays indicated that AHFT-4 had evolved broad-spectrum cross-resistance to ALS-inhibiting herbicides of all five chemical families tested, with GR50 resistance index (RI) values ranging from 21 to 206. However, it remained susceptible to the photosystem II inhibitor isoproturon. Pretreatment with the cytochrome P450 inhibitor malathion or the glutathione S-transferase inhibitor 4-chloro-7-nitrobenzoxadiazole had no significant effects on the resistance of AHFT-4 to mesosulfuron-methyl. To our knowledge, this study reports for the first time the ALS gene Pro-197-Ala substitution conferring broad-spectrum cross-resistance to ALS-inhibiting herbicides in A. aequalis.

Hypersonic laminar flow over a canonical 25°–55° double cone is studied using computational fluid dynamics and global stability analysis (GSA) with a free-stream Mach number of 11.5 and various unit Reynolds numbers. Axisymmetric simulations reveal that secondary separation occurs beneath the primary separation bubble beyond a critical Reynolds number. The numerical results agree well with existing experiments and the triple-deck theory with the axisymmetric effect on the incoming boundary layer treated by the Mangler transformation. The GSA identifies a three-dimensional global instability that is azimuthally periodic immediately prior to the emergence of secondary separation. The criterion of the onset of global instability in terms of a scaled deflection angle established for supersonic compression corner flows (Hao et al., J. Fluid Mech., vol. 919, 2021, A4) can be directly applied to double-cone flows. As the Reynolds number is further increased, the flow is strongly destabilized with the coexistence of multiple stationary and low-frequency oscillating unstable modes. Direct numerical simulations confirm that the supercritical double-cone flow is intrinsically three-dimensional, unsteady and exhibits strong azimuthal variations in the peak heating.

The aim of the present study was to compare the rate of preterm birth (PTB) and growth from birth to 18 years between twins conceived by in vitro fertilization (IVF) and twins conceived by spontaneous conception (SC) in mainland China. The retrospective cohort study included 1164 twins resulting from IVF and 25,654 twins conceived spontaneously, of which 494 from IVF and 6338 from SC were opposite-sex twins. PTB and low birth weight (LBW), and growth, including length/height and weight, were compared between the two groups at five stages: infancy (0 year), toddler period (1–2 years), preschool (3–5 years), primary or elementary school (6–11 years), and adolescence (10–18 years). Few statistically significant differences were found for LBW and growth between the two groups after adjusting for PTB and other confounders. Twins born by IVF faced an increased risk of PTB compared with those born by SC (adjusted odds ratio [aOR] 8.21, 95% confidence interval [CI] [3.19, 21.13], p < .001 in all twins and aOR 10.12, 95% CI [2.32, 44.04], p = .002 in opposite-sex twins). Twins born by IVF experienced a similar growth at five stages (0–18 years old) when compared with those born by SC. PTB risk, however, is significantly higher for twins conceived by IVF than those conceived by SC.

Across Eurasia, horse transport transformed ancient societies. Although evidence for chariotry is well dated, the origins of horse riding are less clear. Techniques to distinguish chariotry from riding in archaeological samples rely on elements not typically recovered from many steppe contexts. Here, the authors examine horse remains of Mongolia's Deer Stone-Khirigsuur (DSK) Complex, comparing them with ancient and modern East Asian horses used for both types of transport. DSK horses demonstrate unique dentition damage that could result from steppe chariotry, but may also indicate riding with a shallow rein angle at a fast gait. A key role for chariots in Late Bronze Age Mongolia helps explain the trajectory of horse use in early East Asia.

The widespread occurrence of late Mesozoic volcanic rocks in SE China is associated with widespread mineralization. Most geologists have accepted the model of Pacific plate subduction beneath the eastern Asian continent, but there are still controversies, especially the initial timing of the tectonic transition. In order to understand the tectonic evolution of the palaeo-Pacific plate subduction, an integrated study of zircon U–Pb, Lu–Hf isotope compositions and whole-rock geochemistry was carried out for Mesozoic volcanic rocks in eastern Fujian Province. According to the field observations and zircon U–Pb ages, these volcanic rocks can be divided into three phases: an early stage of Late Jurassic volcanic rocks (Phase 1, 159–153 Ma), a late stage of Late Jurassic volcanic rocks (Phase 2, 152–146 Ma) and an early stage of Early Cretaceous volcanic rocks (Phase 3, 143–139 Ma). Overall, these volcanic rocks are composed of intermediate–acid pyroclastic rocks and lava, with high SiO2, Na2O, K2O and Al2O3 contents, belonging to the high-K calc-alkaline and peraluminous series, with enrichment in large ion lithophile and light rare earth elements but depletion in high-field-strength elements and heavy rare earth elements. However, the Phase 1 and 2 volcanic rocks contain different zircon Hf isotopic compositions and whole-rock geochemistry to the Phase 3 volcanic rocks, implying that they have a different petrogenesis. Our study combined with previous research shows that the decreasing zircon ϵHf(t) values of the Middle–Late Jurassic volcanic rocks indicate a decreasing mantle-derived material contribution. On the contrary, the majority of the Early Cretaceous volcanic rocks have variable ϵHf(t) values, requiring varied degrees of involvement of juvenile components in their origin. Thus, we consider that the Late Jurassic volcanic rocks were generated in a compressional tectonic environment during the early stage (> 146 Ma) of palaeo-Pacific subduction. In contrast, the Cretaceous volcanic rocks were formed in an extensional tectonic setting during a later stage (< 143 Ma) of subduction.

This study examined the contribution of long-term use of Lipiodol capsules, as a supplement to iodised salt to the control of iodine deficiency disorders among women in Xinjiang of China. A total of 1220 women across Kashgar, Aksu, Turpan and Yili Prefectures were surveyed in 2017. Lipiodol capsules were administered twice yearly in Kashgar and once yearly in Aksu and Turpan, but not in Yili. Urinary iodine concentration (UIC), free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroglobulin antibody, thyroid peroxidase antibody and thyroid volume values were assessed. All the women in the four areas were in a state of non-iodine deficiency by UIC. The UIC were higher than adequate in Kashgar and Aksu (619·4 v. 278·6 μg/l). Thyroid hormone levels differed significantly in Turpan and Yili (FT3: 4·4 v. 4·6 pmol/l, FT4: 13·8 v. 14·2 pmol/l, TSH: 2·0 v. 2·7 mIU/l), but did not differ significantly in Kashgar, Aksu and Yili. The four areas did not differ significantly with regard to thyroid nodules, autoimmune thyroiditis or goitre. However, the detection rates of subclinical hypothyroidism (16·6 %) and total thyroid dysfunction (25·4 %) were higher among women in Yili. The supplementation with Lipiodol capsules had improved the iodine nutrition status of women in iodine-deficient areas of Xinjiang since 2006. To avoid negative effects of excess iodine, we suggest a gradual discontinuation of Lipiodol capsules in women with special needs based on the existing iodine nutrition level of local women.

The Antarctic subglacial drilling rig (ASDR) is designed to recover 105 mm-diameter ice cores up to 1400 m depth and 41.5 mm-diameter bedrock cores up to 2 m in length. In order to ensure safe and convenient drilling, drilling auxiliaries are designed to support fieldwork and servicing. These auxiliaries are subdivided into several systems for power supply, drill tripping in the borehole, ice core and chip processing, and drill servicing and maintenance. The required equipment also includes two generators, a drilling winch with a cable, logging winch with a cable, control desk, pipe handler with a fixed clamp, chip chamber vibrator, centrifuge, emergency devices and fitting and electrical tools. Additionally, several environmental protective measures such as a new liquid-tight casing with a thermal casing shoe and a bailing device for recovering drilling fluid from the borehole were designed. Most of the auxiliaries were tested during the summer of 2018–2019 near Zhongshan Station, East Antarctica while drilling to the bedrock to a depth of 198 m.

Drilling to the bedrock of ice sheets and glaciers offers unique opportunities for examining the processes occurring in the bed. Basal and subglacial materials contain important paleoclimatic and paleoenvironmental records and provide a unique habitat for life; they offer significant information regarding the sediment deformation beneath glaciers and its effects on the subglacial hydraulic system and geology. The newly developed and tested Antarctic subglacial drilling rig (ASDR) is designed to recover ice and bedrock core samples from depths of up to 1400 m. All of the drilling equipment is installed inside a movable, sledge-mounted, temperature-controlled and wind-protected drilling shelter and workshop. To facilitate helicopter unloading of the research vessel, the shelter and workshop can be disassembled, with individual parts weighing <2–3 tons. The entire ASDR system weighs ~55 tons, including transport packaging. The ASDR is designed to be transported to the chosen site via snow vehicles and would be ready for drilling operations within 2–3 d after arrival. The ASDR was tested during the 2018–2019 summer season near Zhongshan Station, East Antarctica. At the test site, 2-week drilling operations resulted in a borehole that reached bedrock at a depth of 198 m.