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Rhein, a component derived from rhubarb, has been proven to possess anti-inflammatory properties. Here, we show that rhein mitigates obesity by promoting adipose tissue thermogenesis in diet-induced obese mice. We construct a macrophage-adipocyte co-culture system and demonstrate that rhein promotes adipocyte thermogenesis through inhibiting NLRP3 inflammasome activation in macrophages. Moreover, clues from acetylome analysis identify SIRT2 as a potential drug target of rhein. We further verify that rhein directly interacts with SIRT2 and inhibits NLRP3 inflammasome activation in a SIRT2-dependent way. Myeloid knockdown of SIRT2 abrogates adipose tissue thermogenesis and metabolic benefits in obese mice induced by rhein. Together, our findings elucidate that rhein inhibits NLRP3 inflammasome activation in macrophages by regulating SIRT2, and thus promotes white adipose tissue thermogenesis during obesity. These findings uncover the molecular mechanism underlying the anti-inflammatory and anti-obesity effects of rhein, and suggest that rhein may become a potential drug for treating obesity.

Abstract Breast cancer is one of the most prevalent and diverse malignancies, and, with global cases increasing, the need for biomarkers to inform individual sensitivity to chemotherapeutics has never been greater. Our retrospective clinical analysis predicted that the expression of the fragile site-associated tumor suppressor (FATS) gene was associated with the sensitivity of breast cancer to neoadjuvant chemotherapy with paclitaxel. In vitro experiments subsequently demonstrated that FATS significantly increased the inhibitory effects of paclitaxel on breast cancer cells’ migration, growth, and survival. An interaction screen revealed that FATS interacted with MYH9 and promoted its degradation via the ubiquitin-proteasome pathway, thereby downregulating Wnt signaling. By overexpressing FATS and MYH9, we demonstrated that FATS enhanced paclitaxel-induced apoptosis in breast cancer cells by degrading MYH9 to downregulate the Wnt pathway. We also demonstrated in a mouse xenograft model that FATS significantly increased the chemosensitivity of breast cancer cells to paclitaxel in vivo. This study presents a new mechanism by which FATS interacts with MYH9 to suppress the Wnt/β-catenin signaling pathway and induce apoptosis, thus enhancing the sensitivity of breast cancer cells to paclitaxel chemotherapy. The results also propose novel biomarkers for predicting breast cancer sensitivity to neoadjuvant chemotherapy with paclitaxel. Finally, we provide in vivo evidence that the combination of paclitaxel with IWR-1, a novel Wnt pathway inhibitor, synergistically suppresses breast cancer growth, laying the foundation for future trials with this drug combination. These results therefore provide a number of potential solutions for more precise treatment of patients with breast cancer in the future.

Abstract Rhein, a component derived from rhubarb, has been proven to possess anti-inflammatory properties. Here, we show that rhein mitigates obesity by promoting adipose tissue thermogenesis in diet-induced obese mice. We construct a macrophage-adipocyte co-culture system and demonstrate that rhein promotes adipocyte thermogenesis through inhibiting NLRP3 inflammasome activation in macrophages. Moreover, clues from acetylome analysis identify SIRT2 as a potential drug target of rhein. We further verify that rhein directly interacts with SIRT2 and inhibits NLRP3 inflammasome activation in a SIRT2-dependent way. Myeloid knockdown of SIRT2 abrogates adipose tissue thermogenesis and metabolic benefits in obese mice induced by rhein. Together, our findings elucidate that rhein inhibits NLRP3 inflammasome activation in macrophages by regulating SIRT2, and thus promotes white adipose tissue thermogenesis during obesity. These findings uncover the molecular mechanism underlying the anti-inflammatory and anti-obesity effects of rhein, and suggest that rhein may become a potential drug for treating obesity.

Abnormal proliferation of aggressive fibroblast-like synoviocytes (FLS) and perpetuate synovial inflammation can inevitably accelerate the progression of rheumatoid arthritis (RA). Herein, a strategy of simultaneously promoting FLS apoptosis and inhibiting inflammation as mediated by macrophages is proposed to restore synovial homeostasis for effective RA therapy. A hyaluronic acid-based dissolvable microneedle (MN) is fabricated for transdermal delivery of dual human serum albumin (HSA)-contained biomimetic nanocomplexes to regulate RA FLS and macrophages. Upon skin insertion, dual nanocomplexes are released rapidly from the MN and accumulate in RA joint microenvironment through both passive and active targeting as mediated by HSA. Thioketal-crosslinked fluorinated polyethyleneimine 1.8 K (TKPF) was constructed to bind the plasmid encoding pro-apoptotic gene PUMA with HSA coating layer (TKPF/pPUMA@HSA, TPH). TPH nanocomplexes can upregulate PUMA through RA FLS transfection to trigger efficient apoptosis. Also, HSA nanocomplexes encapsulating the classic anti-inflammatory natural product celastrol (Cel@HSA, CH) can inhibit inflammation of macrophages through blocking NF-κB pathway activation. TPH/CH MN can deplete RA FLS and inhibit M1 macrophage activation, suppress synovial hyperplasia as well as reduce bone and cartilage erosion in a collagen-induced arthritis (CIA) mouse model, demonstrating a promising strategy for efficient RA treatment.

The research progress in chemical crosslinking and filler enhancement of tetrapropyl fluoro elastomer was reviewed at home and abroad with 39 references. The key roles of co-crosslinkers and fillers were elucidated in the construction of crosslinking networks. The aging mechanism of tetrapropyl fluoro elastomer was summarized syste-matically under environmental conditions such as heat, oxygen, acid and alkali, and hydrogen sulfide.

Abstract Elastocaloric cooling has emerged as an eco-friendly technology capable of eliminating greenhouse-gas refrigerants. However, its development is limited by the large driving force and low efficiency in uniaxial loading modes. Here, we present a low-force and energy-efficient elastocaloric air cooling approach based on coil-bending of NiTi ribbons/wires. Our air cooler achieves continuous cold outlet air with a temperature drop of 10.6 K and a specific cooling power of 2.5 W g−1 at a low specific driving force of 26 N g−1. Notably, the cooler shows a system coefficient of performance of 3.7 (ratio of cooling power to rotational mechanical power). These values are realized by the large specific heat transfer area (12.6 cm2 g−1) and the constant cold zone of NiTi wires. Our coil-bending system exhibits a competitive performance among caloric air coolers.

Normalizing inflamed soils including reactive oxygen species (ROS), nitric oxide (NO), cell-free DNA, and regulating inflammation-related seeds such as macrophages, neutrophils, fibroblasts, represent a promising strategy to maintain synovial tissue homeostasis for rheumatoid arthritis (RA) treatment. Herein, ROS scavenging amphiphilic block copolymer PEGylated bilirubin and NO-scavenging PEGylated o-phenylenediamine were fabricated to self-assemble into a dually responsive nanoparticle loaded with JAK inhibitor notopterol (Not@BR/oPDA-PEG, NBOP NPs). The simultaneous ROS and NO depletion combined with JAK-STAT pathway inhibition could not only promote M2 polarization to reduce further ROS and NO generation, but also decrease cytokines and chemokines to prevent immune cell recruitment. Specifically, NBOP NPs responded to high level ROS and NO, and disintegrated to release notopterol in inflamed joints as the hydrophobic heads BR and oPDA were transformed into hydrophilic ones. The released notopterol could inhibit the JAK-STAT pathway of inflammatory cells to reduce the secretion of pro-inflammatory cytokines and chemokines. This strategy represented an effective way to regulate RA soils and seeds through breaking the positive feedback loop of inflammation aggravation, achieving an excellent anti-RA efficacy in a collagen-induced arthritis rat model. Taken together, our work offered a reference to adjust RA soils and seeds for enhanced RA treatment.

Background: The objective of the study was to systematically evaluate the efficacy and safety of semaglutide in overweight or obese adults with or without type 2 diabetes. Materials and Methods: The study, registered with PROSPERO (CRD42023450979), was designed as a systematic review and meta-analysis. Using a combination of subject matter and free words, a comprehensive search of Embase, PubMed, and Cochrane Library databases was performed to identify randomized controlled trials of semaglutide in overweight or obese adults with or without Type 2 diabetes mellitus from January 1, 2020, to July 14, 2023. The primary outcomes were the changes in body weight and adverse drug reaction (ADR). Random or fixed effects models were used in meta-analysis, pooling data as relative risks (RRs) or mean difference (MD) with 95% confidence intervals (CIs). Cochrane Collaboration’s Risk of Bias tool was used to assess quality. Meta-analysis was performed using RevMan 5.3. Results: A total of 2490 publications were retrieved. Fifteen publications were finally included, totaling 6984 overweight or obese adult patients. Meta-analysis showed that compared with the control group, the semaglutide group was reduced more significantly in body weight (MD = −7.49, 95% CI [−9.92, −5.07], P < 0.001), body mass index (MD = −3.35, 95% CI [−4.79, −1.92], P < 0.001), waist circumference (MD = −7.26, 95% CI [−9.94, −4.58], P < 0.001), as well as glycosylated hemoglobin (RR = −0.66, 95% CI [−1.07, −0.25], P = 0.002), fasting blood glucose values (RR = −4.81, 95% CI [−7.03, −2.60], P < 0.001), and systolic blood pressure (RR = −3.37, 95% CI [−5.32, −1.42], P < 0.001), and the proportion of patients who lost > 5%, 10%, 15%, and 20% of their overall body weight, respectively (RR = 3.19, 95% CI [1.89, 5.36], P < 0.001), (RR = 4.74, 95% CI [2.78, 8.11], P < 0.001), (RR = 6.17, 95% CI [3.88, 9.82], P < 0.001), and (RR = 9.14, 95% CI [6.05, 13.80], P < 0.001) were also superior to the control group. Regarding safety, the incidence of total ADR in the semaglutide group was close to the placebo group. Still, gastrointestinal adverse effects such as nausea, vomiting, abdominal pain, and diarrhea were higher than those in the control group. Conclusion: Semaglutide can effectively lose weight in overweight or obese adults with or without diabetes, potentially providing cardiovascular benefits; however, gastrointestinal adverse should be closely monitored.

Objectives: To investigate gadolinium deposition in the liver and brain in a rat model with liver fibrosis (LF) after intravenous administration of gadoxetate disodium (GD) and the histological effects of gadolinium deposition in the liver and brain. Methods: Adult male Sprague–Dawley rats were randomly assigned to one of the three groups: 1) LF group received intraperitoneal injection of carbon tetrachloride (CCl4) for 9 weeks alone; 2) LF&GD group received CCl4 and intravenous administration of GD (for 5 consecutive days); 3) GD group received olive oil and GD. Seven days after the final injection of GD, the deep cerebellar nuclei (DCN) and liver were excised to determine gadolinium concentrations via inductively coupled plasma mass spectrometry, and histologic staining was performed. Bonferroni's post-hoc test and Wilcoxon rank sum test were used to compare the differences between the three groups. Results: The concentrations of retained gadolinium in the liver in the LF&GD group (2.18 ± 0.44 μg/g) were significantly greater compared to the LF group (0.02 ± 0.01 μg/g, P

This review summarizes commonly used hospital-based healthcare quality evaluation systems at home and abroad, and focuses on evaluation indicators regarding patient safety. Through the comparative analysis between different evaluation systems, it tries to shed light on China's healthcare quality evaluation system, especially the indicators related to patient safety. The purpose of this review is to understand and learn from foreign evaluation systems on patient safety, which can help further improve the quality of healthcare in China.

BackgroundAlthough many young Chinese women migrate to urban regions for better opportunities, little is known about the prevalence and awareness of having high blood pressure (HBP) in this population. This study investigated the prevalence, awareness, and factors associated with HBP among young female migrant workers in Central South China.MethodsWe conducted a cross-sectional study to identify HBP (2017 ACC/AHA guidelines) among female migrant workers aged 18-45 years in Central South China. Demographics, anthropometric measurements, hypertension-related lifestyle, awareness of HBP, and blood pressure were recorded. Logistic regression analysis was used to identify the factors associated with HBP (blood pressure ≥ 130/80 mmHg).ResultsOverall, 232 female migrants participated in the study (mean age 34.4; standard deviation: 6.4 years). The prevalence of HBP was 27.2% (95% CI [21.6-33.2]), and 88.9% of the participants were unaware of their HBP status. Having rural medical insurance (odds ratio [OR] = 20.7; 95% confidence interval 95% CI [2.1-204.8]), awareness of having HBP (OR = 5.1; 95% CI [1.4-18.5]), physical inactivity (OR = 2.9; 95% CI [1.1-7.9]), and being overweight/obese (OR = 2.7; 95% CI [1.3-6.1]) were independently associated with HBP.ConclusionsThis study revealed a high prevalence of HBP among young Chinese female migrant workers, as well as a high frequency of being unaware of their condition and some associated factors (rural medical insurance, awareness of having HBP, physical inactivity, and overweight/obesity). The uncontrolled HBP among young Chinese female migrant workers suggested that health education needs further promotion in such a population.

[Objective] Livestock and poultry farming manure pollution, the high cost of manure resource use of input problems has become an important constraint on the sustainable development of large-scale dairy farms in China, through the exploration of farm manure resource use technology adoption behavioural mechanisms and their economic effects, for technology promotion, energy saving and emission reduction has an important role in promoting. [Methods] Based on the survey data of 218 large-scale dairy farms in 15 provinces in China and using net income and environmental efficiency to comprehensively reflect the economic effects of manure resource utilization technology adoption, this study used the Probit and propensity score matching (PSM) models to investigate the influencing factors of manure resource utilization technology adoption behavior of farms of different scales, and evaluate the economic effects of the adoption of manure resource utilization technologies in different scale farms. [Results] In terms of technology adoption decisions, the adoption of faecal resource utilisation technology on moderate farms was significantly associated with the age of the farm manager, farming density, proportion of technicians, type of milking machine, nature of the farm, and environmental regulations; the adoption of faecal resource utilisation technology on large-scale farms was mainly affected by environmental regulations such as environmental constraints and incentive policies, as well as by farming density. In terms of economic effects, the environmental efficiency and net returns of large-scale farms were higher than those of moderate-scale farms, and the adoption of manure resource utilisation technology could increase the net returns and environmental efficiency of moderate-scale farms by about 26% and 6%, respectively, and could improve the environmental efficiency of large-scale farms by about 4%, with little effect on their net returns. [Conclusion] The pressure of manure treatment can be effectively alleviated by improving the supervision and support system of livestock and poultry manure, strengthening the technical training of breeding personnel, and promoting moderate scale breeding. In the future, it is still necessary to provide basic support for the utilization of fecal waste resources through scientific and technological innovation and technology promotion, and promote the high-quality development of animal husbandry.

This paper briefly describes the theoretical basis of the DRY-1B capacitive component drilling strain gauge (drilling strain gauge). It discusses critical technologies such as micro-displacement sensing, noise reduction, temperature control, performance testing, and calibration. The strain gauge achieved high resolution (≥5×10−11ε), wideband (10–100 Hz optional), extensive dynamic range (≥1×10−3ε), 24-bit AD recording, low power consumption (< 3W), and other technical indicators. Its performance is better than the United States PBO and Japan borehole strain gauge of the same period, and it is an international leading long-term observation instrument for crustal movement, which can basically meet the observation requirements of creep movement with slow accumulation of long-term strain and seismic and volcanic activity with a rapid change of short-term strain. Since 2008, through the application of more than 20 geostress stations, the borehole strain gauge has recorded a large amount of strain information, such as crustal deformation, fault activity, co-seismic strain wave, strain step, and ore pressure activity. Based on the results of the self-consistency test of strain monitoring data of the geostress station in the Beichangshan Mountain and the analysis of seismic mapping capacity of the Turkey earthquake, it is found that the strain curves of the 1#+3# and 2#+4# capacitance sensors at the Beichangshan Mountain stress station are generally stable, and the correlation coefficient R2 is 0.95. The annual variation rate of the differential strain of 1#–3# and 2#–4# elements is 10−8 magnitude, which reflects that the shear stress is dominant in the Long Island area and the stress environment of seismic activity is relatively high. The strain gauge was used to observe the apparent co-seismic strain response of Turkey’s M 7.8 and M 7.5 earthquakes on February 6, 2023. In particular, it obtained the M 7.8 main seismic surface wave period of 50–60 s, presenting an out-facing wave anomaly. Theoretically, the strain wave generated by the M 0.74 earthquakes within 100 km can be distinguished, and the application demonstration effect has been achieved. The borehole strain gauge has good popularization value and application prospects in geodynamics research and internal dynamic geological disaster monitoring.

The article reviews the development of the volumetric borehole strain gauge. In response to the current problems of insufficient stability and bandwidth and low calibration accuracy of the volumetric strain gauge, a TY-2B-type small volumetric borehole strain gauge was developed with innovative improvements in the hydraulic sensor, control circuit, and calibration method. The improved hydraulic sensor improves the accuracy and reduces the instrument’s volume; the improved control circuit increases the sampling rate, bandwidth, and the instrument’s stability; the innovative piezoelectric ceramic calibration technology raises the reliability of the monitoring data. The test results show that the improved TY-2B volumetric strain gauge has a low power consumption of less than 3 W, good long-term stability, high sensitivity with a resolution of 10-11 ε, and suitable high-frequency and low-frequency. It has a sampling rate of 100 Hz and can acquire complete seismic strain waveforms with precise and stable solid tide waveforms. It is small and light, with a reduced outer diameter of Φ89 mm for Φ100 mm drilling, a length of 1300 mm, and a weight of 45 kg for easy transport and installation. After 15 years of laboratory and field station testing, it obtained good monitoring data and demonstrated its highly sensitive seismic reflection capability. The observed response of the volumetric strain station in the northern section of Longmen Mountain to the 2010 Yushu earthquake and the 2023 Turkey earthquake shows that the TY-series high-precision volumetric strain gauge is not only a static strain gauge but also a broad-frequency strain seismograph with dynamic-static calibration capability. It has a unique advantage over pendulum seismometers in that it can observe both the long-term slow deformation and accumulation of deformation in the earth’s crust and the transient subtle features of crustal rupture and deformation. The long-term trends of the monitoring curves obtained from the Qingchuan–Hanzhong volumetric strain stations since the Wenchuan earthquake and the Guangzhou station since 2021 are consistent with the regional geological characteristics reflected by the seismic and tectonic geological data, indicating that the TY-2B volumetric strain gauge can meet the needs of geological scientific research and geological hazard observation.

In order to obtain the in-situ stress field characteristics and analyze tectonic stability in the Motuo key area of the eastern Himalayan syntaxis, the in-situ stress measurement of one in-situ stress hole and 11 test sections of the Xirang section of the Motuo fault zone were carried out by the hydraulic fracturing method. The results show that the maximum and minimum horizontal principal stress values (SH, Sh) in the test section of 61.43−121.34 m are 3.05−14.50 MPa and 2.16−9.87 MPa, respectively, and the vertical principal stress values (Sv) are 1.63−3.31 MPa, namely, SH>Sh>Sv. The in-situ stress field at the measuring point is dominated by horizontal compression, and all of them belong to the in-situ stress state of reverse fault. The principal stress values gradually increase with the increase of depth, and the dominant direction of the maximum principal stress is NEE. In the whole range of in-situ stress depth, the lateral pressure coefficients (Kav) are 1.39−4.38, the maximum horizontal stress coefficients (KHv) are greater than 1, and the ratio increases with the increase of depth. The regional stress field of this key area is dominated by horizontal stress and it is highly directional. The horizontal stress coefficients (KHh) of all test sections are 1.23−1.66, which are similar to the calculation results of in-situ stress characteristic parameters in Linzhi−Tongmai section. The horizontal tectonic stress of the shallow level at 98 m is relatively small, and the stress accumulation level is low. The friction coefficient required to maintain fault stability is smaller than the critical friction coefficient of actual fault, and the tectonic environment is relatively stable. When the depth exceeds 98 m, the friction coefficient required to maintain fault stability is close to the critical friction coefficient value of the actual fault due to the dominant role of horizontal tectonic stress, and there is a small risk of fault instability slip. The superposition of the Coulomb stress change in the sinistral strike-slip direction and the thrust direction caused by the strong regional earthquakes on the fault plane of the Motuo fault zone in the study area are all negative numbers, which inhibits fault slip and does not increase the risk of fault activity in the study area.

Abstract Background Histone modification is an important epigenetic regulatory mechanism and essential for stress adaptation in plants. However, systematic analysis of histone modification genes (HMs) in Brassicaceae species is lacking, and their roles in response to abiotic stress have not yet been identified. Results In this study, we identified 102 AtHMs, 280 BnaHMs, 251 BcHMs, 251 BjHMs, 144 BnHMs, 155 BoHMs, 137 BrHMs, 122 CrHMs, and 356 CsHMs in nine Brassicaceae species, respectively. Their chromosomal locations, protein/gene structures, phylogenetic trees, and syntenies were determined. Specific domains were identified in several Brassicaceae HMs, indicating an association with diverse functions. Syntenic analysis showed that the expansion of Brassicaceae HMs may be due to segmental and whole-genome duplications. Nine key BnaHMs in allotetraploid rapeseed may be responsible for ammonium, salt, boron, cadmium, nitrate, and potassium stress based on co-expression network analysis. According to weighted gene co-expression network analysis (WGCNA), 12 BnaHMs were associated with stress adaptation. Among the above genes, BnaPRMT11 simultaneously responded to four different stresses based on differential expression analysis, while BnaSDG46, BnaHDT10, and BnaHDA1 participated in five stresses. BnaSDG46 was also involved in four different stresses based on WGCNA, while BnaSDG10 and BnaJMJ58 were differentially expressed in response to six different stresses. In summary, six candidate genes for stress resistance (BnaPRMT11, BnaSDG46, BnaSDG10, BnaJMJ58, BnaHDT10, and BnaHDA1) were identified. Conclusions Taken together, these findings help clarify the biological roles of Brassicaceae HMs. The identified candidate genes provide an important reference for the potential development of stress-tolerant oilseed plants.

Abstract Haemoglobin E (HbE) β-thalassaemia causes approximately 50% of all severe thalassaemia worldwide; equating to around 30,000 births per year. HbE β-thalassaemia is due to a point mutation in codon 26 of the human HBB gene on one allele (GAG; glutamatic acid → AAG; lysine, E26K), and any mutation causing severe β-thalassaemia on the other. When inherited together in compound heterozygosity these mutations can cause a severe thalassaemic phenotype. However, if only one allele is mutated individuals are carriers for the respective mutation and have an asymptomatic phenotype (β-thalassaemia trait). Here we describe a base editing strategy which corrects the HbE mutation either to wildtype (WT) or a normal variant haemoglobin (E26G) known as Hb Aubenas and thereby recreates the asymptomatic trait phenotype. We have achieved editing efficiencies in excess of 90% in primary human CD34 + cells. We demonstrate editing of long-term repopulating haematopoietic stem cells (LT-HSCs) using serial xenotransplantation in NSG mice. We have profiled the off-target effects using a combination of circularization for in vitro reporting of cleavage effects by sequencing (CIRCLE-seq) and deep targeted capture and have developed machine-learning based methods to predict functional effects of candidate off-target mutations.

With the rapid development of electric vehicles (EVs) in Chinese cities, accurately forecasting the number of EVs used by urban residents in the next five years and more long term is beneficial for the government to adjust industrial policies of EVs, guide the rational planning of urban charging facilities and supporting distribution network, and achieve the rational and orderly development of the EV industry. The paper considers the advantages of using the grey GM(1,1) prediction model to predict the short-term ownership of EVs by urban residents. Then, by forecasting the number of EV users in a certain city in the future and predicting the number of private vehicles in the future, the boundary conditions for long-term year ownership of EVs by residents are determined. Combined with historical data and short-term forecast data generated by the grey prediction model, the model parameters that include the innovation coefficient and imitation coefficient of the Bass model are trained using a genetic algorithm. Finally, the Bass model is used for medium- to long-term ownership forecasting from 2023 to 2040. The prediction error for the target year is provided. The simulation results indicate that the ownership of resident EVs in this city will experience rapid growth in the next five years.