Excessive or sustained endoplasmic reticulum stress: one of the culprits of adipocyte dysfunction in obesity.

As the prevalence of obesity continues to rise globally, the research on adipocytes has attracted more and more attention. In the presence of nutrient overload, adipocytes are exposed to pressures such as hypoxia, inflammation, mechanical stress, metabolite, and oxidative stress that can lead to organelle dysfunction. Endoplasmic reticulum (ER) is a vital organelle for sensing cellular pressure, and its homeostasis is essential for maintaining adipocyte function. Under conditions of excess nutrition, ER stress (ERS) will be triggered by the gathering of abnormally folded proteins in the ER lumen, resulting in the activation of a signaling response known as the unfolded protein responses (UPRs), which is a response system to relieve ERS and restore ER homeostasis. However, if the UPRs fail to rescue ER homeostasis, ERS will activate pathways to damage cells. Studies have shown a role for disturbed activation of adipocyte ERS in the pathophysiology of obesity and its complications. Prolonged or excessive ERS in adipocytes can aggravate lipolysis, insulin resistance, and apoptosis and affect the bioactive molecule production. In addition, ERS also impacts the expression of some important genes. In view of the fact that ERS influences adipocyte function through various mechanisms, targeting ERS may be a viable strategy to treat obesity. This article summarizes the effects of ERS on adipocytes during obesity.

Simulation of osteotomy in total knee arthroplasty with femoral extra-articular deformity assisted by artificial intelligence: a study based on three-dimensional models.

BACKGROUND: The impact of extra-articular deformities (EADs) on lower limb alignment and collateral ligament integrity during total knee arthroplasty (TKA) poses significant challenges, increasing surgical complexity. Our study aims to evaluate the influence of EADs on mechanical axis alignment and the risk of collateral ligament injury during TKA using an AI-assisted surgical planning system, with the goal of minimizing ligament damage through precise and scientific planning. METHODS: A healthy volunteer underwent CT and MRI scans of the lower limbs. The scan images were imported into Mimics 20.0 software, and the reconstructed models were spatially aligned using 3-maticResearch 11.0 software. Using Unigraphics NX9.0 software, 50 three-dimensional models of femoral lateral joint deformities with varying positions and angles were created. Finally, TKA was simulated using the AI JOINT preoperative planning system. RESULTS: The larger the deformity angle and the closer it is to the knee joint, the more pronounced the deviation of the mechanical axis. During MA-aligned osteotomy, nine types of deformities can damage the collateral ligaments. After adjusting the varus/valgus of the prosthesis within a safe range of 3° and leaving a residual 3° varus/valgus in the lower limb alignment, only the 25° varus and 25° valgus deformities located at 90% of the femoral anatomical axis remain uncorrected. CONCLUSION: For patients with osteoarthritis and concurrent EAD undergoing TKA, using reconstructed 3D models of the collateral ligaments for preoperative planning helps visually assess collateral ligament damage, providing a practical solution. Minimizing intra-articular osteotomies within a safe range and allowing some residual alignment deviation can reduce the risk of collateral ligament injury.

Route of Delivery in a Patient with Vaginal Stenosis from Stevens-Johnson Syndrome and Review of the Management of Genital Complications.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe dermatological conditions, predominantly affecting women with mortality rates of 4.8-48%. Antibiotics are common triggers. They cause painful mucous membrane erosions in various body parts. Treatment involves steroids, creams, and therapy. Pregnant women with SJS-related vaginal stenosis face challenges of delivery route. Case Report: A 34-year-old primigravida woman presented at term with vaginal stenosis consequent to a 10-year-history of Stevens-Johnson syndrome triggered by cephalosporin. On pediatric Pederson speculum examination, vaginal stenosis, adhesion, scarred cervix, telangiectasis of the vaginal mucosa, and moderate bleeding after examination were noted. The risks of severe genital tract laceration and excessive bleeding from vaginal birth was discussed with the couple. Shared clinical decision making was reached to undergo a cesarean delivery. Conclusion: SJS and TEN can result in severe genital complications in women, sometimes requiring cesarean sections due to genital scarring.

Efficient conversion of hemicellulose into high-value product and electric power by enzyme-engineered bacterial consortia.

As an abundant agricultural and forestry biomass resource, hemicelluloses are hard to be effectively degraded and utilized by microorganisms due to the constraints of membrane and metabolic regulations. Herein, we report a synthetic extracellular metabolic pathway with hemicellulose-degrading-enzymes controllably displayed on Escherichia coli surface as engineered bacterial consortia members for efficient utilization of xylan, the most abundant component in hemicellulose. Further, we develop a hemicellulose/O2 microbial fuel cell (MFC) configuring of enzyme-engineered bacterial consortia based bioanode and bacterial-displayed laccase based biocathode. The optimized MFC exhibited an open-circuit voltage of 0.71 V and a maximum power density (Pmax) of 174.33 ± 4.56 µW cm-2. Meanwhile, 46.6% (w/w) α-ketoglutarate was produced in this hemicellulose fed-MFC. Besides, the MFC retained over 95% of the Pmax during 6 days' operation. Therefore, this work establishes an effective and sustainable one-pot process for catalyzing renewable biomass into high-value products and electricity in an environmentally-friendly way.

The Ethics of Placebo.

This article reviews the ethical implications related to the use of placebos in clinical practice and clinical trials. We discuss evidence for placebo effects, the role of placebo in research and clinical practice, and related ethical issues. It also provides an overview of some of the new findings related to research involving placebos and the possible associated ethical challenges.

The effect of copper and vitamin D on osteoarthritis outcomes: A Mendelian randomization study.

This study aimed to explore the causal relationship between trace elements and osteoarthritis (OA). The results showed a relatively weak association between copper and OA, while vitamin D showed a significant positive association with OA. Mendelian randomization (MR) analysis was used to investigate the causal relationship between copper and vitamin D and OA. A variety of MR methods including inverse variance weighting, weighted median, MR-Egger, simple model, and multi-text mixed model were analyzed to confirm the consistency of these results. Sensitivity analysis further confirmed the reliability of these causal relationships and excluded the interference of pleiotropy. These findings add to the understanding of the potential role of micronutrients in the prevention and treatment of OA and support the idea of vitamin D as a potential therapy for the prevention and treatment of OA. Future studies should further explore the specific biological mechanisms of these trace elements and the differences in their effects in different populations in order to develop more effective treatment strategies to reduce the health burden of degenerative joint diseases.

Exclusive enteral nutrition initiates individual protective microbiome changes to induce remission in pediatric Crohn's disease.

Exclusive enteral nutrition (EEN) is a first-line therapy for pediatric Crohn's disease (CD), but protective mechanisms remain unknown. We established a prospective pediatric cohort to characterize the function of fecal microbiota and metabolite changes of treatment-naive CD patients in response to EEN (German Clinical Trials DRKS00013306). Integrated multi-omics analysis identified network clusters from individually variable microbiome profiles, with Lachnospiraceae and medium-chain fatty acids as protective features. Bioorthogonal non-canonical amino acid tagging selectively identified bacterial species in response to medium-chain fatty acids. Metagenomic analysis identified high strain-level dynamics in response to EEN. Functional changes in diet-exposed fecal microbiota were further validated using gut chemostat cultures and microbiota transfer into germ-free Il10-deficient mice. Dietary model conditions induced individual patient-specific strain signatures to prevent or cause inflammatory bowel disease (IBD)-like inflammation in gnotobiotic mice. Hence, we provide evidence that EEN therapy operates through explicit functional changes of temporally and individually variable microbiome profiles.

Systematic synthesis and identification of monolignol pathway metabolites.

Monolignol serves as the building blocks to constitute lignin, the second abundant polymer on Earth. Despite two decades of diligent efforts, complete identification of all metabolites in the currently proposed monolignol biosynthesis pathway has proven elusive. This limitation also hampers their potential application. One of the primary obstacles is the challenge of assembling a collection of all molecules, because many are commercially unavailable or prohibitively costly. In this study, we established systematic pipelines to synthesize all 24 molecules through the conversions between functional groups on a core structure followed by the application to other core structures. We successfully identified all of them in Populus trichocarpa and Eucalyptus grandis, two representative species respectively from malpighiales and myrtales in angiosperms. Knowledge about monolignol metabolite chemosynthesis and identification will form the foundation for future studies.

Regulating the surface charge and reactivity of cellulose through quaternized modification to achieve salt-free reactive dyeing process.

Limited research exists on how the structure of quaternary ammonium salt (QAS) affects the electrostatic attraction and hydroxyl reactivity of cationic cotton, which strongly affects reactive dye adsorption, diffusion, and fixation. Thus, in our work, the effects of QAS structure on the electrostatic attraction, hydroxyl reactivity, and dyeing properties were investigated. The intensity at 402.5 eV (-N+(CH3)3) in the XPS rose from 34 % to 70 % as the QAS alkyl chain length increased from 4 to 18 carbon atoms, signifying an enhancement of the positive charge and electrostatic attraction between reactive dye and QAS modified cotton. However, molecular dynamic (MD) simulations of the QAS-modified cotton with octadecyl chains revealed that the reactive dye demonstrated slower molecular mobility compared to the untreated cotton. This is not conducive to the diffusion and fixation of reactive dyes. The QAS-modified cotton with hexyl chains not only alters the activity of hydroxyl at the 6th but also generates additional hydroxyl at the ß-position that contributes to enhancing the improvement of fixation through Gaussian simulations. Therefore, cationic cotton treated with 60 g/L of (3-chloro-2-hydroxypropyl)-dimethyl-octadecylazanium chloride (CT-8) exhibits superior dye uptake levels (91.84 %), K/S values (13.10), and dye fixation percent (88.38 %).

The functional role of m6A demethylase ALKBH5 in cardiomyocyte hypertrophy.

Cardiomyocyte hypertrophy is a major outcome of pathological cardiac hypertrophy. The m6A demethylase ALKBH5 is reported to be associated with cardiovascular diseases, whereas the functional role of ALKBH5 in cardiomyocyte hypertrophy remains confused. We engineered Alkbh5 siRNA (siAlkbh5) and Alkbh5 overexpressing plasmid (Alkbh5 OE) to transfect cardiomyocytes. Subsequently, RNA immunoprecipitation (RIP)-qPCR, MeRIP-qPCR analysis and the dual-luciferase reporter assays were applied to elucidate the regulatory mechanism of ALKBH5 on cardiomyocyte hypertrophy. Our study identified ALKBH5 as a new contributor of cardiomyocyte hypertrophy. ALKBH5 showed upregulation in both phenylephrine (PE)-induced cardiomyocyte hypertrophic responses in vitro and transverse aortic constriction (TAC)/high fat diet (HFD)-induced pathological cardiac hypertrophy in vivo. Knockdown or overexpression of ALKBH5 regulated the occurrence of hypertrophic responses, including the increased cardiomyocyte surface areas and elevation of the hypertrophic marker levels, such as brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP). Mechanically, we indicated that ALKBH5 activated JAK2/STAT3 signaling pathway and mediated m6A demethylation on Stat3 mRNA, but not Jak2 mRNA, resulting in the phosphorylation and nuclear translocation of STAT3, which enhances the transcription of hypertrophic genes (e.g., Nppa) and ultimately leads to the emergence of cardiomyocytes hypertrophic growth. Our work highlights the functional role of ALKBH5 in regulating the onset of cardiomyocyte hypertrophy and provides a potential target for hypertrophic heart diseases prevention and treatment. ALKBH5 activated JAK2/STAT3 signaling pathway and mediated m6A demethylation on Stat3 mRNA, but not Jak2 mRNA, resulting in the phosphorylation and nuclear translocation of STAT3, which enhances the transcription of hypertrophic genes (e.g., Nppa) and ultimately leads to the emergence of cardiomyocytes hypertrophic growth.

Progress in Computer-Assisted Navigation for Total Knee Arthroplasty in Treating Knee Osteoarthritis with Extra-Articular Deformity.

Total knee arthroplasty (TKA) is a well-established treatment for end-stage knee osteoarthritis. However, in patients with concomitant extra-articular deformities, conventional TKA techniques may lead to unsatisfactory outcomes and higher complication rates. This review summarizes the application of navigated TKA for treating knee osteoarthritis with extra-articular deformities. The principles and potential benefits of computer navigation systems, including improved component alignment, soft tissue balancing, and restoration of mechanical axis, are discussed. Research studies demonstrate that navigated TKA can effectively correct deformities, relieve pain, and improve postoperative joint function and quality of life compared with conventional methods. The advantages of navigated TKA in terms of surgical precision, lower complication rates, and superior functional recovery are highlighted. Despite challenges like the learning curve and costs, navigated TKA is an increasingly indispensable tool for achieving satisfactory outcomes in TKA for knee osteoarthritis patients with extra-articular deformities.

The diagnostic value of a nomogram based on enhanced CT radiomics for differentiating between intrahepatic cholangiocarcinoma and early hepatic abscess.

Objective: This study aimed to investigate the value of a CT-enhanced scanning radiomics nomogram in distinguishing between early hepatic abscess (EHA) and intrahepatic cholangiocarcinoma (ICC) and to validate its diagnostic efficacy. Materials and Methods: Clinical and imaging data on 112 patients diagnosed with EHA and ICC who underwent double-phase CT-enhanced scanning at our hospital were collected. The contours of the lesions were delineated layer by layer across the three phases of CT scanning and enhancement using 3D Slicer software to define the region of interest (ROI). Subsequently, the contours were merged into 3D models, and radiomics features were extracted using the Radiomics plug-in. The data were randomly divided into training (n = 78) and validation (n = 34) cohorts at a 7:3 ratio, using the R programming language. Standardization was performed using the Z-score method, and LASSO regression was used to select the best λ-value for screening variables, which were then used to establish prediction models. The rad-score was calculated using the best radiomics model, and a joint model was constructed based on the rad-score and clinical scores. A nomogram was developed based on the joint model. The diagnostic efficacy of the models for distinguishing ICC and EHA was assessed using receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses. Calibration curves were used to evaluate the reliability and accuracy of the nomograms, while decision curves and clinical impact curves were utilized to assess their clinical value. Results: Compared with the ICC group, significant differences were observed in clinical data and imaging characteristics in the EHA group, including age, centripetal enhancement, hepatic pericardial depression sign, arterial perfusion abnormality, arterial CT value, and arteriovenous enhancement (p < 0.05). Logistic regression analysis identified centripetal enhancement, hepatic pericardial depression sign, arterial perfusion abnormality, arterial CT value, and arteriovenous enhancement as independent influencing factors. Three, five, and four radiomics features were retained in the scanning, arterial, and venous phases, respectively. Single-phase models were constructed, with the radiomics model from the arterial phase demonstrating the best diagnostic efficacy. The rad-score was calculated using the arterial-phase radiomics model, and nomograms were drawn in conjunction with the clinical model. The nomogram based on the combined model exhibited the highest differential diagnostic efficacy between EHA and ICC (training cohort: AUC of 0.972; validation cohort: AUC of 0.868). The calibration curves indicated good agreement between the predicted and pathological results, while decision curves and clinical impact curves demonstrated higher clinical utility of the nomograms. Conclusion: The CT-enhanced scanning radiomics nomogram demonstrates high clinical value in distinguishing between EHA and ICC, thereby enhancing the accuracy of preoperative diagnosis.

Stabilization of Organic Cations in Lead Halide Perovskite Solar Cells Using Phosphine Oxides Derivatives.

Preventing ion migration in perovskite photovoltaics is key to achieving stable and efficient devices. The activation energy for ion migration is affected by the chemical environment surrounding the ions. Thus, the migration of organic cations in lead halide perovskites can be mitigated by engineering their local interactions, for example through hydrogen bonding. Ion migration also leads to ionic losses via interfacial reactions. Undesirable reactivities of the organic cations can be eliminated by introducing protecting groups. In this work, we report bis(2-oxo-3-oxazolidinyl) phosphinic chloride (BOP-Cl) as a perovskite ink additive with the following benefits: (1) The phosphoryl and two oxo groups form six-membered intermolecular hydrogen-bonded rings with the formamidinium cation (FA), mitigating ion migrations. (2) The hydrogen bonding reduces the electrophilicity of the ammonium protons by donating electron density, therefore reducing its reactivity with the surface oxygen on the metal oxide. Furthermore, the molecule can react to form a protecting group on the nucleophilic oxygen at the tin oxide transport layer surface through the elimination of chlorine. As a result, we achieve perovskite solar cells with an efficiency of 25.0% and improved MPP stability T93 = 1200 h at 40-45 °C compared to a control device (T86 = 550 h). In addition, we show a negative correlation between the strength of hydrogen bonding of different phosphine oxide derivatives to the organic cations and the degree of metastable behavior (e.g., initial burn-in) of the device.

Mitochondria-Targeted Multifunctional Nanoprodrugs by Inhibiting Metabolic Reprogramming for Combating Cisplatin-Resistant Lung Cancer.

How to address the resistance of cisplatin (CDDP) has always been a clinical challenge. The resistance mechanism of platinum-based drugs is very complex, including nuclear DNA damage repair, apoptosis escape, and tumor metabolism reprogramming. Tumor cells can switch between mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis and develop resistance to chemotherapy drugs through metabolic variability. In addition, due to the lack of histone protection and a relatively weak damage repair ability, mitochondrial DNA (mtDNA) is more susceptible to damage, which in turn affects mitochondrial OXPHOS and can become a potential target for platinum-based drugs. Therefore, mitochondria, as targets of anticancer drugs, have become a hot topic in tumor resistance research. This study constructed a self-assembled nanotargeted drug delivery system LND-SS-Pt-TPP/HA-CD. ß-Cyclodextrin-grafted hydronic acid (HA-CD)-encapsulated prodrug nanoparticles can target CD44 on the tumor surface and further deliver the prodrug to intracellular mitochondria through a triphenylphosphine group (TPP+). Disulfide bonds can be selectively degraded by glutathione (GSH) in mitochondria, releasing lonidamine (LND) and the cisplatin prodrug (Pt(IV)). Under the action of GSH and ascorbic acid, Pt(IV) is further reduced to cisplatin (Pt(II)). Cisplatin can cause mtDNA damage, induce mitochondrial dysfunction and mitophagy, and then affect mitochondrial OXPHOS. Meanwhile, LND can reduce the hexokinase II (HK II) level, induce destruction of mitochondria, and block energy supply by glycolysis inhibition. Ultimately, this self-assembled nano targeted delivery system can synergistically kill cisplatin-resistant lung cancer cells, which supplies an overcome cisplatin resistance choice via the disrupt mitochondria therapy.

Exploring the genetic association between immune cells and susceptibility to osteonecrosis using large-scale population data.

Objectives: Research shows a close association between aberrant immune reactions in osteonecrotic tissues and immune cell infiltration. However, due to limitations in sample size and dataset comprehensiveness, the causal relationship between them is not fully established. This study aims to determine whether there is a causal relationship using a larger and more diverse dataset. Methods: We conducted a comprehensive Mendelian Randomization (MR) analysis to investigate the causal relationship between immune cell characteristics and osteonecrosis. Utilizing publicly available genetic data, we explored the causal relationships between 731 immune cell features and 604 cases from the FinnGen Finnish database, as well as 257 cases from the UK Biobank database with osteonecrosis data. The inverse-variance weighted (IVW) method was used for the primary analysis, and we employed sensitivity analyses to assess the robustness of the main results. In addition, considering data from the two databases used in this study, a meta-analysis was conducted on the significant immune cells associated with osteonecrosis (FDR <0.05). Results: our findings suggested that specific immune cell signatures, such as CD20- % lymphocytes, CD62L-monocytes, and CD33br HLA DR+ CD14-cells were associated with increased odds of osteonecrosis. In contrast, EM CD4+ activated cells and DP (CD4+ CD8+) T cells were associated with decreased odds. Notably, osteonecrosis was associated with a potential decrease in CD45 on immature MDSC cell content. Conclusion: From a genetic perspective, we demonstrated a close association between immune cells and osteonecrosis. These findings significantly enhance our understanding of the interplay between immune cell infiltration and the risk of osteonecrosis, contributing to the potential design of therapeutic strategies from an immunological standpoint.

Clinical efficacy of Ni-Ti memory alloy four-corner arthrodesis concentrator in the treatment of scaphoid nonunion advanced collapse: a follow-up of over 10 years.

PURPOSE: Exploring the therapeutic effects of Ni-Ti shape memory alloy four-corner arthrodesis concentrator (NT-FCAC) in treating scaphoid nonunion advanced collapse (SNAC) and providing a decade-long follow-up report. MATERIALS AND METHODS: Twenty-six patients with SNAC underwent scaphoidectomy, along with four-corner arthrodesis fusion involving the capitate, lunate, triquetrum, and hamate, using NT-MFCAC. Grip strength was measured using a Jamar dynamometer, while wrist joint mobility was assessed using a goniometer. Preoperative and postoperative assessments were conducted using the Quick Disabilities of the Arm, Shoulder, and Hand (Quick DASH) questionnaire to monitor limb functionality restoration. Pain levels at the wrist joint were evaluated using the visual analog scale (VAS). Postoperative wrist bone fusion status was assessed through anteroposterior and lateral radiographs of the wrist joint. RESULTS: After a 3-month postoperative period, all 26 patients exhibited osseous union at the wrist joint. Over a follow-up spanning 10-15 years, no severe postoperative complications were observed in any patient. Grip strength in the affected side of all patients recovered to 81.96% compared to the healthy side, while wrist joint mobility in the affected side reached over 60% of the healthy side's functionality. VAS scores decreased significantly from 5.85 ± 0.73 preoperatively to 0.19 ± 0.40 at the final follow-up; Quick DASH scores reduced from 69.88 ± 5.12 preoperatively to 6.30 ± 1.25 at final follow-up. Statistically significant differences were noted in VAS and Quick DASH scores for all patients (p < 0.05). However, beyond 60 months postoperatively, subsequent follow-ups did not yield statistically significant differences in VAS and Quick DASH scores for all patients (p > 0.05). CONCLUSIONS: Utilizing NT-FCAC for SNAC treated with four-corner arthrodesis fusion results in a high rate of wrist bone fusion, preserving a significant portion of wrist joint function and exhibiting favorable long-term outcomes. This approach is suitable for treating patients with SNAC requiring four-corner arthrodesis fusion.

Association between genetically plasma proteins and osteonecrosis: a proteome-wide Mendelian randomization analysis.

Background: Previous studies have explored the role of plasma proteins on osteonecrosis. This Mendelian randomization (MR) study further assessed plasma proteins on osteonecrosis whether a causal relationship exists and provides some evidence of causality. Methods: Summary-level data of 4,907 circulating protein levels were extracted from a large-scale protein quantitative trait loci study including 35,559 individuals by the deCODE Genetics Consortium. The outcome data for osteonecrosis were sourced from the FinnGen study, comprising 1,543 cases and 391,037 controls. MR analysis was conducted to estimate the associations between protein and osteonecrosis risk. Additionally, Phenome-wide MR analysis, and candidate drug prediction were employed to identify potential causal circulating proteins and novel drug targets. Results: We totally assessed the effect of 1,676 plasma proteins on osteonecrosis risk, of which 71 plasma proteins had a suggestive association with outcome risk (P < 0.05). Notably, Heme-binding protein 1 (HEBP1) was significant positively associated with osteonecrosis risk with convening evidence (OR, 1.40, 95% CI, 1.19 to 1.65, P = 3.96 × 10-5, P FDR = 0.044). This association was further confirmed in other MR analysis methods and did not detect heterogeneity and pleiotropy (all P > 0.05). To comprehensively explore the health effect of HEBP1, the phenome-wide MR analysis found it was associated with 136 phenotypes excluding osteonecrosis (P < 0.05). However, no significant association was observed after the false discovery rate adjustment. Conclusion: This comprehensive MR study identifies 71 plasma proteins associated with osteonecrosis, with HEBP1, ITIH1, SMOC1, and CREG1 showing potential as biomarkers of osteonecrosis. Nonetheless, further studies are needed to validate this candidate plasma protein.

Research on triaxial compressive mechanical properties and damage constructive model of post-thawing double-fractured quasi-sandstones with different angles.

Joints and fractures lead to different failure mechanisms in rock masses under different environments. The mechanical properties and failure mechanisms of rocks with fissures are key problems in rock mass engineering. Parallel double-fracture quasi-sandstone specimens with different dip angles were prepared and subjected to triaxial compression tests after a single freeze-thaw cycle. Pore development, crack propagation, damage evolution, and failure characteristics were analysed. Combined with the strength distribution theory of microelements and the static elastic modulus theory, a damage constitutive model of double-fracture quasi-sandstone under freeze-thaw cycles and loads was established. This study explored the pore development, fracture propagation, damage evolution, and failure characteristics of fractured sandstone after thawing. The results showed that the compression wave velocity of the thawed specimens decreased, the nuclear magnetic resonance (NMR) T2 curve shifted to the right, and the frost heave force promoted the development of the internal porosity in the specimens. With an increase in the crack dip angle, peak stress, expansion stress, cohesion and internal friction angle, the specimen showed a 'U' shaped change trend, compression cracks, and rock bridge penetration rate after failure decreased, and mixed failure of tension and shear gradually changed into shear failure. When the dip angles were 30° and 60°, the double fractured quasi-sandstone had larger total damage and more obvious brittle failure characteristics.

Single-cell RNA sequencing reveals the CRTAC1+ population actively contributes to the pathogenesis of spinal ligament degeneration by SPP1+ macrophage.

Degenerative spinal stenosis is a chronic disease that affects the spinal ligaments and associated bones, resulting in back pain and disorders of the limbs among the elderly population. There are few preventive strategies for such ligament degeneration. We here aimed to establish a comprehensive transcriptomic atlas of ligament tissues to identify high-priority targets for pharmaceutical treatment of ligament degeneration. Here, single-cell RNA sequencing was performed on six degenerative ligaments and three traumatic ligaments to understand tissue heterogeneity. After stringent quality control, high-quality data were obtained from 32,014 cells. Distinct cell clusters comprising stromal and immune cells were identified in ligament tissues. Among them, we noted that collagen degradation associated with CTHRC1+ fibroblast-like cells and calcification linked to CRTAC1+ chondrocyte-like cells were key features of ligament degeneration. SCENIC analysis and further experiments identified ATF3 as a key transcription factor regulating the pathogenesis of CRTAC1+ chondrocyte-like cells. Typically, immune cells infiltrate localized organs, causing tissue damage. In our study, myeloid cells were found to be inflammatory-activated, and SPP1+ macrophages were notably enriched in degenerative ligaments. Further exploration via CellChat analysis demonstrated a robust interaction between SPP1+ macrophages and CRTAC1+ chondrocyte-like cells. Activated by SPP1, ATF3 propels the CRTAC1/MGP/CLU axis, fostering ligament calcification. Our unique resource provides novel insights into possible mechanisms underlying ligament degeneration, the target cell types, and molecules that are expected to mitigate degenerative spinal ligament. We also highlight the role of immune regulation in ligament degeneration and calcification, enhancing our understanding of this disease.

[Research progress of type 2 inflammation-related tissue remodeling in nasal polyps].

Chronic rhinosinusitis with nasal polyps is a common chronic inflammatory disease with significant tissue remodeling, but the mechanism of remodeling remains unclear. Studies have shown that Type（T） 2 inflammatory network plays a crucial role in tissue remodeling and nasal polyp formation. Clinical trials have been carried out for several biological targets, and a number of potential therapeutic targets have received increasing attention. This paper will summarize the research progress of T2 inflammatory response involved in nasal polyp tissue remodeling to provide ideas for further exploring the mechanism of nasal polyp tissue remodeling.