RESUMEN

Sterile inflammation occurs in various chronic diseases due to many nonmicrobe factors. Examples include endometrial hyperplasia (EH), endometriosis, endometrial cancer, and breast cancer, which are all sterile inflammation diseases induced by estrogen imbalances. However, how estrogen-induced sterile inflammation regulates EH remains unclear. Here, a single-cell RNA-Seq is used to show that SHP2 upregulation in endometrial endothelial cells promotes their inflammatory activation and subsequent transendothelial macrophage migration. Independent of the initial estrogen stimulation, IL1ß and TNFα from macrophages then create a feedforward loop that enhances endothelial cell activation and IGF1 secretion. This endothelial cell-macrophage interaction sustains sterile endometrial inflammation and facilitates epithelial cell proliferation, even after estradiol withdrawal. The bulk RNA-Seq results and phosphoproteomic analysis show that endothelial SHP2 mechanistically enhances RIPK1 activity by dephosphorylating RIPK1Tyr380. This event activates downstream activator protein 1 (AP-1) and instigates the inflammation response. Furthermore, targeting SHP2 using SHP099 (an allosteric inhibitor) or endothelial-specific SHP2 deletion alleviates endothelial cell activation, macrophage infiltration, and EH progression in mice. Collectively, the findings demonstrate that SHP2 mediates the transition of endothelial activation from estradiol-driven acute inflammation to macrophage-amplified chronic inflammation. Targeting sterile inflammation mediated by endothelial cell activation is a promising strategy for nonhormonal intervention in estrogen-related diseases.

RESUMEN

Background: Effective glycemic control is crucial for hospitalized patients, leading to benefits such as shorter hospital stays and reduced postoperative infection rates. While previous studies have emphasized the effectiveness of multidisciplinary collaborative stewardship for hospital-wide hyperglycemia management, patient perspectives and preferences have not been adequately considered. Objective: To identify factors influencing treatment preferences of Chinese hospitalized diabetes patients using discrete choice experiments (DCEs) and provide practical insights for the construction of a hospital-wide glycemic control programme. Methods: A face-to-face survey was conducted among diabetes patients admitted to nonendocrine departments in a tertiary hospital in Nanjing, China. The attributes and levels were determined based on DCE principles, and a conditional logit model was used to quantify patients' preferences. Results: A total of 157 respondents were analyzed. Antihyperglycemic effectiveness, healthcare providers, treatment regimen, monitoring frequency, and adverse reactions were the five attributes that significantly influenced patient preference (p < 0.05). Notably, an 80% glycemic control rate (ß = 2.009) and a multidisciplinary management team involving clinical pharmacists (ß = 1.346) had the greatest impact. Negative effects were observed for hypoglycemia (ß = -1.008), insulin pump use (ß = -0.746), and frequent glucose monitoring (ß = -0.523). Female patients exhibited higher concern for healthcare providers (ß = 1.172) compared to males. Younger and shorter-course patients prioritized antihyperglycemic effectiveness (ß = 3.330, ß = 1.510), while older patients preferred multidisciplinary management (ß = 1.186) and opposed increased monitoring frequency (ß = -0.703). Patients with higher educational backgrounds showed greater acceptance of continuous glucose monitoring (ß = 1.983), and those with higher annual income placed more emphasis on glycemic control rate. Conclusion: Treatment preferences of hospitalized diabetes patients are mainly influenced by antihyperglycemic effectiveness, adverse reactions, healthcare providers, and individual characteristics. Comprehensive consideration and an individualized therapy strategy should be given when constructing a hospital-wide glycemic control programme.

Asunto(s)

RESUMEN

Purpose: Parkinson's disease (PD) is a common neurodegenerative disease that severely affects patients' daily lives and places a significant burden on the global economy. There are currently no specific biomarkers for distinguishing between the different stages of PD. Methods: We divided 78 mice into six equal groups, including five model PD groups (W1-W5; based on the PD stage induced by length of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/propofol induction time) and a control group. Then, we used metabolomics technology to detect the serum small-molecule metabolites present in each group. Ultimately, we screened for potential biomarkers using the variable importance in the projection of the orthogonal partial least squares discriminant analysis and the coefficient value of LASSO ordinal logistic regression. Results: We identified 12 potential biomarkers, including dehydroepiandrosterone sulfate, pipecolic acid, N-acetylleucine, 2-aminoadipic acid, L-tyrosine, uric acid, and 5-hydroxyindoleacetaldehyde. Pathway analysis revealed their involvement in amino acid metabolism, caffeine metabolism, steroid hormone biosynthesis, and purine metabolism. Additionally, the receiver operating characteristic curve indicated that a biomarker panel comprising the 12 biomarkers could differentiate between the different PD stages. Conclusion: Different PD stages are characterized by different metabolites. The biomarkers identified in this study are helpful to understand the PD process.

RESUMEN

CSF1R-related disorder (CSF1R-RD) is a neurodegenerative condition that predominantly affects white matter due to genetic alterations in the CSF1R gene, which is expressed by microglia. We studied an elderly man with a hereditary, progressive dementing disorder of unclear etiology. Standard genetic testing for leukodystrophy and other neurodegenerative conditions was negative. Brain autopsy revealed classic features of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), including confluent white matter degeneration with axonal spheroids and pigmented glial cells in the affected white matter, consistent with CSF1R-RD. Subsequent long-read sequencing identified a novel deletion in CSF1R that was not detectable with short-read exome sequencing. To gain insight into potential mechanisms underlying white matter degeneration in CSF1R-RD, we studied multiple brain regions exhibiting varying degrees of white matter pathology. We found decreased CSF1R transcript and protein across brain regions, including intact white matter. Single nuclear RNA sequencing (snRNAseq) identified two disease-associated microglial cell states: lipid-laden microglia (expressing GPNMB, ATG7, LGALS1, LGALS3) and inflammatory microglia (expressing IL2RA, ATP2C1, FCGBP, VSIR, SESN3), along with a small population of CD44+ peripheral monocyte-derived macrophages exhibiting migratory and phagocytic signatures. GPNMB+ lipid-laden microglia with ameboid morphology represented the end-stage disease microglia state. Disease-associated oligodendrocytes exhibited cell stress signatures and dysregulated apoptosis-related genes. Disease-associated oligodendrocyte precursor cells (OPCs) displayed a failure in their differentiation into mature myelin-forming oligodendrocytes, as evidenced by upregulated LRP1, PDGFRA, SOX5, NFIA, and downregulated NKX2-2, NKX6.2, SOX4, SOX8, TCF7L2, YY1, ZNF488. Overall, our findings highlight microglia-oligodendroglia crosstalk in demyelination, with CSF1R dysfunction promoting phagocytic and inflammatory microglia states, an arrest in OPC differentiation, and oligodendrocyte depletion.

Asunto(s)

RESUMEN

Acetaminophen (APAP) overdose is a major cause of drug-induced liver injury. Sirtuins 5 (SIRT5) has been implicated in the development of various liver diseases. However, its involvement in APAP-induced acute liver injury (AILI) remains unclear. The present study aimed to explore the role of SIRT5 in AILI. SIRT5 expression is dramatically downregulated by APAP administration in mouse livers and AML12 hepatocytes. SIRT5 deficiency not only exacerbates liver injury and the inflammatory response, but also worsens mitochondrial oxidative stress. Conversely, the opposite pathological and biochemical changes are observed in mice with SIRT5 overexpression. Mechanistically, quantitative succinylome analysis and site mutation experiments revealed that SIRT5 desuccinylated aldehyde dehydrogenase 2 (ALDH2) at lysine 385 and maintained the enzymatic activity of ALDH2, resulting in the suppression of inflammation and mitochondrial oxidative stress. Furthermore, succinylation of ALDH2 at lysine 385 abolished its protective effect against AILI, and the protective effect of SIRT5 against AILI is dependent on the desuccinylation of ALDH2 at K385. Finally, virtual screening of natural compounds revealed that Puerarin promoted SIRT5 desuccinylase activity and further attenuated AILI. Collectively, the present study showed that the SIRT5-ALDH2 axis plays a critical role in AILI progression and might be a strategy for therapeutic intervention.

RESUMEN

Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis and inflammatory cell infiltration. The traditional Chinese medicine prescription, Bitongqing (BTQ) exhibited significant efficacy in the clinical treatment of RA. However, the potential therapeutic mechanisms of BTQ in treating RA have not been fully investigated. This study aims to elucidate the effect of BTQ on collagen-induced arthritis (CIA) rat macrophage pyroptosis, providing a theoretical basis for treating RA. Methods: This research employed liquid chromatography-mass spectrometry (LC-MS) to identify the primary components of BTQ. The therapeutic effects of BTQ were evaluated in a rat model of CIA. In vivo experiments were conducted using pathohistological staining, immunofluorescence, micro-CT, and Western blotting. Next, Mouse leukemia cells of monocyte macrophage cells (RAW264.7) were induced to undergo pyroptosis using lipopolysaccharide (LPS) and adenosine triphosphate (ATP), and the impact of BTQ on RAW264.7 macrophages was assessed through cell viability, immunofluorescence analysis, lactate dehydrogenase (LDH) secretion measurement, and Western blotting. Results: BTQ had a therapeutic effect on CIA rats, which was mainly manifested as a reduction in joint inflammation, foot swelling, bone erosion, and amelioration of pathological changes in these rats. Further studies revealed that BTQ inhibited the levels of cytokine production interleukin-18 (IL-18) and interleukin-1ß (IL-1ß), and likewise, it inhibited the expression of key proteins in the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) mediated pyroptosis in the synovial tissues of CIA rats. The results of in vitro experiments demonstrated that BTQ attenuated LDH secretion, decreased IL-18 and IL-1ß cytokine production, and downregulated expression of key proteins involved in the NLRP3-mediated pyroptosis on RAW264.7 macrophages. Conclusion: The therapeutic potential of BTQ in CIA lies in its ability to inhibit NLRP3-mediated macrophage pyroptosis, thereby suggesting a promising strategy for the treatment of RA.

RESUMEN

To overcome the poor targeting of conventional chemotherapeutic drugs and the defects of low drug-loading capacity of conventional drug delivery systems, novel drug delivery systems with high drug-loading capacity are developed. Herein, the high drug-loaded mPEG79-GFLGDDD-DOX copolymer is first synthesized via an amide reaction, which can bond multiplex DOX. After PEGylation, the drug can resist the adsorption of proteins in the plasma in blood circulation, avoid being rapidly cleared out of the body, and prolong the circulation time of the drug in the blood, which is conducive to the enrichment of micelles in tumor tissues through the EPR effect. In tumor tissues, the peptide Glycine- Phenylalanine- Leucine- Glycine (GFLG) is recognized and sheared by overexpressed cathepsin B, which stripped the outer layer of methoxy polyethylene glycol (mPEG) and made it more readily available for uptake by tumor cells. After entering the tumor cells, the bonded DOX and the physically encapsulated DOX in the micelles played a synergistic role, realizing the killing of tumor cells, thus effectively enhancing the therapeutic effect on tumors. The findings in this work suggest that a high drug-loading drug delivery system has great potential in the clinical treatment of tumors.

RESUMEN

OBJECTIVE: To compare the outcomes of intelligent first-aid training based on virtual reality (VR) among individuals with different demographic characteristics. METHODS: A total of 50 nonmedical professional volunteers from Nanchang were conveniently sampled in March 2021. All participants underwent intelligent VR first-aid training, and a comparative analysis was conducted by dividing them into different groups based on demographic characteristics. RESULTS: Male participants had a lower chest compression interruption time compared to female participants (7.40 ± 0.50 vs. 8.04 ± 0.56, t = -4.231, p < 0.001). Additionally, male participants had a higher proportion of compressions with correct compression depth (81.33 ± 1.24 vs. 79.78 ± 1.48, t = 4.038, p < 0.001), higher mean ventilation volume (518.11 ± 1.50 vs. 516.61 ± 2.17, t = 2.881, p = 0.006), and higher theoretical knowledge test score (8.74 ± 0.59 vs. 8.00 ± 0.43, t = 4.981, p < 0.001). There were statistically significant differences in the mean chest compression frequency (110.38 ± 5.74 vs. 105.00 ± 4.78 vs. 107.80 ± 5.97, F = 5.187, p = 0.009) among participants with different educational backgrounds. Pairwise comparisons showed that technical degree holders had a higher mean chest compression frequency than bachelor's degree holders, whereas no statistically significant difference was observed between master's degree holders and bachelor's degree holders. CONCLUSION: The outcomes of first-aid training differ among participants of different genders and with different educational backgrounds. With all participants meeting the training qualifications, it is believed that the application of intelligent VR first-aid training platforms can improve the first aid capabilities of the public.

RESUMEN

Millettia speciosa Champ, renowned for its diverse applications in traditional medicine, is extensively cultivated in the Guangxi region of China, spanning roughly 5,973 hectares. In July 2021, a plantation in Yulin, Guangxi, China (22°64'N; 110°29'E), exhibited severe leaf spot disease on M. speciosa. Notably, a 46,690 square meters area had over 40% leaf spot incidence. Initially, symptoms appeared as small, circular, pale-yellow lesions on the leaves, then turned into irregular, dark brown spots with yellow halos, leading to the wilt and defoliation of leaves. To identify the responsible pathogen, a total of five symptomatic leaves were collected and sterilized systematically. Small tissue segments (5×5 mm) from lesion peripheries were aseptically excised, then surface sterilized with 75% ethanol for 10 s, and 1% sodium hypochlorite (NaClO) for 3 min. Following this, the sterilized tissues were triple-rinsed with sterile water and cultured on potato dextrose agar (PDA) at 28 °C in the dark for 7 d. A total of seven isolates were obtained through single-spore isolation, and one representative isolate, N2-3, was selected for further analysis. After 7 d of incubation, colonies displayed flat, white, and extensively branched aerial hyphae. Over time, the reverse side of the colony changed from white to yellowish-white. The pycnidia were black with conidial droplets ranging from cream to pale yellow exuding from their ostioles. The α-conidia were one-celled, hyaline, ovoid to cylindrical, typically with one or two droplets, 2.6 to 5.9 ×1.4 to 3.9 µm (n=50). These morphological traits align with those of the genus Diaporthe, as reported by Li et al. (2022) and Crous et al. (2015). To identify the species, isolate N2-3 underwent sequencing of the internal transcribed spacer (ITS), ß-tubulin (BT), and translation elongation factor 1 alpha (EF1-α) sections (Huang et al. 2021). Obtained sequences of ITS, BT and EF1-α (Genebank accessions nos. OR600532, OR662169 and OR662168) displayed a 99% similarity to Diaporthe tulliensis (Genebank accessions nos. OP219651, ON932382, OL412437, respectively). Based on the concatenated ITS, BT and EF1-α, a neighbor-joining phylogenetic analyses using MEGA7.0 clustered with D. tulliensis. Therefore, the fungus was identified as D. tulliensis (teleomorph name) based on morphological and molecular features. A pathogenicity test was conducted on 1-year-old M. speciosa seedlings by gently abrading healthy leaves with sterilized toothpicks to create superficial wounds. Wounded leaves were then inoculated with 5 mm diameter mycelial plugs, while control seedlings received PDA plugs. Three leaves per plant and five plants per treatment were selected for assessment. All seedlings were kept in a controlled greenhouse (12/12h light/dark, 25 ± 2 °C, 90% humidity). After 7 d, the inoculated leaves showed symptoms like those in the field, while control plants remained healthy. The fungus was consistently reisolated from the infected leaves, satisfying Koch's postulates. Notably, D. tulliensis has caused Boston ivy leaf spot, bodhi tree leaf spot, cacao pod rot, and jasmine stem canker (Huang et al. 2021; Li et al. 2022; Serrato-Diaz et al. 2022; Hsu et al. 2023). This discovery is significant as it marks the first report of Diaporthe tulliensis causing leaf spot on Millettia speciossa in China, which has direct implications for the development of diagnostic tools and research into potential disease management strategies.

RESUMEN

Nanocrystalline metallic materials have the merit of high strength but usually suffer from poor ductility and rapid grain coarsening, limiting their practical application. Here, we introduce a core-shell nanostructure in a multicomponent alloy to address these challenges simultaneously, achieving a high tensile strength of 2.65 GPa, a large uniform elongation of 17%, and a high thermal stability of 1173 K. Our strategy relies on an ordered superlattice structure that excels in dislocation accumulation, encased by a ≈3 nm disordered face-centered-cubic nanolayer acting as dislocation sources. The ordered superlattice with high anti-phase boundary energy retards dislocation motions, promoting their interaction and storage within the nanograins. The disordered interfacial nanolayer promotes dislocation emission and effectively accommodates the plastic strain at grain boundaries, preventing intergranular cracking. Consequently, the order-disorder core-shell nanostructure exhibits enhanced work-hardening capability and large ductility. Moreover, such core-shell nanostructure exhibits high coarsening resistance at elevated temperatures, enabling it high thermal stability. Such a design strategy holds promise for developing high-performance materials.

RESUMEN

The combination of no-till farming and green manure is key to nourishing the soil and increasing crop yields. However, it remains unclear how to enhance the efficiency of green manure under no-till conditions. We conducted a two-factor field trial of silage maize rotated with hairy vetch to test the effects of tillage methods and returning. Factor 1 is the type of tillage, which is divided into conventional ploughing and no-tillage; factor 2 is the different ways of returning hairy vetch as green manure, which were also compared: no return (NM), stubble return (H), mulching (HM), turnover (HR, for CT only), and live coverage (LM, for NT only). Our findings indicate that different methods of returning hairy vetch to the field will improve maize yield and quality. The best results were obtained in CT and NT in HM and LM, respectively. Specifically, HM resulted in the highest dry matter quality and yield, with improvements of 35.4% and 31.9% over NM under CT, respectively. It also demonstrated the best economic and net energy performance. However, other treatments had no significant effect on the beneficial utilization and return of nutrients. The LM improved yields under NT by boosting soil enzyme activity, promoting nitrogen transformation and accumulation, and increasing nitrogen use efficiency for better kernel development. Overall, NTLM is best at utilizing and distributing soil nutrients and increasing silage maize yield. This finding supports the eco-efficient cultivation approach in silage maize production in the region.

RESUMEN

Viral communities exist in a variety of ecosystems and play significant roles in mediating biogeochemical processes, whereas viruses inhabiting strongly alkaline geochemical systems remain underexplored. In this study, the viral diversity, potential functionalities, and virus-host interactions in a strongly alkaline environment (pH = 10.4-12.4) exposed to the leachates derived from the serpentinization-like reactions of smelting slags were investigated. The viral populations (e.g., Herelleviridae, Queuovirinae, and Inoviridae) were closely associated with the dominating prokaryotic hosts (e.g., Meiothermus, Trueperaceae, and Serpentinomonas) in this ultrabasic environment. Auxiliary metabolic genes (AMGs) suggested that viruses may enhance hosts' fitness by facilitating cofactor biosynthesis, hydrogen metabolism, and carbon cycling. To evaluate the activity of synthesis of essential cofactor vitamin B9 by the viruses, a viral folA (vfolA) gene encoding dihydrofolate reductase (DHFR) was introduced into a thymidine-auxotrophic strain Escherichia coli MG1655 ΔfolA mutant, which restored the growth of the latter in the absence of thymidine. Notably, the homologs of the validated vDHFR were globally distributed in the viromes across various ecosystems. The present study sheds new light on the unique viral communities in hyperalkaline ecosystems and their potential beneficial impacts on the coexisting microbial consortia by supplying essential cofactors. IMPORTANCE: This study presents a comprehensive investigation into the diversity, potential functionalities, and virus-microbe interactions in an artificially induced strongly alkaline environment. Functional validation of the detected viral folA genes encoding dihydrofolate reductase substantiated the synthesis of essential cofactors by viruses, which may be ubiquitous, considering the broad distribution of the viral genes associated with folate cycling.

Asunto(s)

RESUMEN

BACKGROUND: Temporal lobe (TL) white matter (WM) injuries are often seen early after radiotherapy (RT) in nasopharyngeal carcinoma patients (NPCs), which fail to fully recover in later stages, exhibiting a "non-complete recovery pattern". Herein, we explored the correlation between non-complete recovery WM injuries and TL necrosis (TLN), identifying dosimetric predictors for TLN-related high-risk WM injuries. METHODS: We longitudinally examined 161 NPCs and 19 healthy controls employing multi-shell diffusion MRI. Automated fiber-tract quantification quantified diffusion metrics within TL WM tract segments. ANOVA identified non-complete recovery WM tract segments one-year post-RT. Cox regression models discerned TLN risk factors utilizing non-complete recovery diffusion metrics. Normal tissue complication probability (NTCP) models and dose-response analysis further scrutinized RT-related toxicity to high-risk WM tract segments. RESULTS: Seven TL WM tract segments exhibited a "non-complete recovery pattern". Cox regression analysis identified mean diffusivity of the left uncinate fasciculus segment 1, neurite density index (NDI) of the left cingulum hippocampus segment 1, and NDI of the right inferior longitudinal fasciculus segment 1 as TLN risk predictors (hazard ratios [HRs] with confidence interval [CIs]: 1.45 [1.17-1.81], 1.07 [1.00-1.15], and 1.15 [1.03-1.30], respectively; all P-values < 0.05). In NTCP models, D10cc.L, D20cc.L and D10cc.R demonstrated superior performance, with TD50 of 37.22 Gy, 24.96 Gy and 37.28 Gy, respectively. CONCLUSIONS: Our findings underscore the significance of the "non-complete recovery pattern" in TL WM tract segment injuries during TLN development. Understanding TLN-related high-risk WM tract segments and their tolerance doses could facilitate early intervention in TLN and improve RT protocols.

Asunto(s)

RESUMEN

BACKGROUND & AIMS: Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) has long been recognized as an adipokine. However, the exact role of eNAMPT in alcoholic liver disease (ALD) and its relevance to brown adipose tissue (BAT) remain largely unknown. This study aimed to evaluate the impact of eNAMPT on liver function and the underlying mechanisms involved in BAT-Liver communication. METHODS: Serum eNAMPT levels were detected in the serum of both ALD patients and mice. Chronic and binge ethanol feeding was used to induce alcoholic liver injury in mice. An eNAMPT antibody, a coculture model of brown adipocytes and hepatocytes, and BAT-specific Nampt knockdown mice were used to investigate the role of eNAMPT in ALD. RESULTS: Serum eNAMPT levels are elevated in ALD patients and are significantly positively correlated with the liver injury index. In ALD mice, neutralizing eNAMPT reduced the elevated levels of circulating eNAMPT induced by ethanol and attenuated liver injury. In vitro experiments revealed that eNAMPT induced hepatocyte ferroptosis through the TLR4-dependent mitochondrial ROS-induced ferritinophagy pathway. Furthermore, ethanol stimulated eNAMPT secretion from brown adipocytes but not from other adipocytes. In the coculture model, ethanol-induced release of eNAMPT from brown adipocytes promoted hepatocyte ferroptosis. In BAT-specific Nampt-knockdown mice, ethanol-induced eNAMPT secretion was significantly reduced, and alcoholic liver injury were attenuated. These effects can be reversed by intraperitoneal injection of eNAMPT. CONCLUSION: Inhibition of ethanol-induced eNAMPT secretion from BAT attenuates liver injury and ferroptosis. Our study reveals a previously uncharacterized critical role of eNAMPT-mediated BAT-Liver communication in ALD and highlights its potential as a therapeutic target.

Asunto(s)

RESUMEN

Introduction: Immune cells are involved in the onset and progression of Sjögren's syndrome (SS). This study explored the causal relationship between immune signature cells and SS, which has not been fully elucidated. Methods: We conducted univariate, multivariate, and bidirectional Mendelian randomization to investigate the causal relationship between 731 immunological feature characteristic cells and SS pairs and explore the interaction of immune cells in SS. Results: After false discovery rate correction, six immune cells were significantly associated with SS risk. Among them, four contributed to SS (CD24 on memory B cell, CD27 on IgD + CD24 + B cell, CD28 on CD39+ secreting CD4 Treg cell, and CD80 on CD62L + mDC); two appeared to reduce SS risk (CD3 on CD39 + CD8 + T cell and CD38 on IgD + CD38 + B cell). Pleiotropy and heterogeneity were not observed. Three immune cells exerted independent effects for SS (CD27 on IgD + CD24 + B cell, CD80 on CD62L + mDC, and CD38 on IgD + CD38 + B cell); two were risk factors (CD27 on IgD + CD24 + B cell and CD80 on CD62L + mDC); and one was a protective factor (CD38 on IgD + CD38 + B cell). Twenty-three immune cells showed a reverse causal relationship with SS. Conclusion: These findings demonstrate the influence of immune cells on SS risk and the effects of SS on immune cells, providing new clues for further research on the mechanisms underlying SS.

RESUMEN

Biological organisms often have remarkable multifunctionality through intricate structures, such as concurrent shape morphing and stiffness variation in the octopus. Soft robots, which are inspired by natural creatures, usually require the integration of separate modules to achieve these various functions. As a result, the whole structure is cumbersome, and the control system is complex, often involving multiple control loops to finish a required task. Here, inspired by the scales that cover creatures like pangolins and fish, we developed a robotic structure that can vary its stiffness and change shape simultaneously in a highly integrated, compact body. The scale-inspired layered structure (SAILS) was enabled by the inversely designed programmable surface patterns of the scales. After fabrication, SAILS was inherently soft and flexible. When sealed in an elastic envelope and subjected to negative confining pressure, it transitioned to its designated shape and concurrently became stiff. SAILS could be actuated at frequencies as high as 5 hertz and achieved an apparent bending modulus change of up to 53 times between its soft and stiff states. We further demonstrated both the versatility of SAILS by developing a soft robot that is amphibious and adaptive and tunable landing systems for drones with the capacity to accommodate different loads.

RESUMEN

Over the past few decades, there have been advancements in the development of high-performance tissue adhesives as alternatives to traditional sutures and staples for rapid and effective wound closure post-surgery. While tissue adhesives offer advantages such as ease of use, short application time, and minimal tissue damage, they also face challenges related to biocompatibility, biodegradability, and adhesive strength. In this study, L-lysine diisocyanate (LDI) and trimethylolpropane (TMP) were utilized as the primary raw materials to produce a prepolymer terminated with NCO, resulting in the development of a new biocompatible polyurethane tissue adhesive (TMP-LDI). Additionally, SiO2 nanoparticles were incorporated into the prepolymer, significantly enhancing the adhesive strength of the TMP-LDI tissue adhesive through the "nanobridging effect," achieving a strength of 170.4 kPa. Furthermore, the SiO2/TMP-LDI tissue adhesive exhibited satisfactory temperature change during curing and degradation performance. In vitro and in vivo studies demonstrated that SiO2/TMP-LDI exhibited good biocompatibility, efficient hemostasis, antimicrobial properties, and the ability to promote wound healing. This research presents a novel approach for the development of tissue adhesives with superior adhesive performance.

RESUMEN

Objective: To characterize BMI in Chinese patients with RA vs US patients and examine its association with joint damage in Chinese patients. Methods: Each of the 1318 patients from a real-world Chinese RA population was first stratified by gender and then individually age-matched with one American RA patient from the US National Health and Nutritional Examination Survey 1999-2018. Data on BMI, bilateral hand radiographs and risk factors at enrolment were collected but radiographs were unavailable for the American patients. Logistic regression was used to evaluate the association of BMI with radiographic joint damage (RJD) in Chinese patients. Results: Chinese patients had a significantly lower BMI [(weighted) median 21.8 vs 29.8 kg/m2; P < 0.001] and a higher prevalence of being underweight (15.2% vs 1.1%; P < 0.05) than their American counterparts. Underweight Chinese patients (BMI <18.5) had higher modified total Sharp scores (median 17 vs 10) and joint space narrowing (JSN) subscores (median 6 vs 2) (both P < 0.05) than normal-weight patients (BMI ≥18.5-<24). After controlling for confounding, continuous BMI was cross-sectionally negatively associated with RJD [adjusted prevalence odds ratio (OR) 0.90 (95% CI 0.85, 0.96)] and JSN [adjusted prevalence OR 0.92 (95% CI 0.87, 0.96)]; being underweight vs normal weight was associated with RJD [adjusted prevalence OR 2.14 (95% CI 1.37, 3.35)] and JSN [adjusted prevalence OR 1.77 (95% CI 1.10, 2.84)]. Conclusion: Low BMI and being underweight were cross-sectionally associated with joint damage in Chinese RA patients, especially JSN, suggesting the clinical importance of identifying underweight patients and focusing on weight gain to prevent joint damage.