Clinical and Imaging Characteristics of Contrast-enhanced Mammography and MRI to Distinguish Microinvasive Carcinoma from Ductal Carcinoma In situ.

RATIONALE AND OBJECTIVES: The prognosis of ductal carcinoma in situ with microinvasion (DCISM) is more similar to that of small invasive ductal carcinoma (IDC) than to pure ductal carcinoma in situ (DCIS). It is particularly important to accurately distinguish between DCISM and DCIS. The present study aims to compare the clinical and imaging characteristics of contrast-enhanced mammography (CEM) and magnetic resonance imaging (MRI) between DCISM and pure DCIS, and to identify predictive factors of microinvasive carcinoma, which may contribute to a comprehensive understanding of DCISM in clinical diagnosis and support surveillance strategies, such as surgery, radiation, and other treatment decisions. MATERIALS AND METHODS: Forty-seven female patients diagnosed with DCIS were included in the study from May 2019 to August 2023. Patients were further divided into two groups based on pathological diagnosis: DCIS and DCISM. Clinical and imaging characteristics of these two groups were analyzed statistically. The independent clinical risk factors were selected using multivariate logistic regression and used to establish the logistic model [Logit(P)]. The diagnostic performance of independent predictors was assessed and compared using receiver operating characteristic (ROC) analysis and DeLong's test. RESULTS: In CEM, the maximum cross-sectional area (CSAmax), the percentage signal difference between the enhancing lesion and background in the craniocaudal and mediolateral oblique projection (%RSCC, and %RSMLO) were found to be significantly higher for DCISM compared to DCIS (p = 0.001; p < 0.001; p = 0.008). Additionally, there were noticeable statistical differences in the patterns of enhancement morphological distribution (EMD) and internal enhancement pattern (IEP) between DCIS and DCISM (p = 0.047; p = 0.008). In MRI, only CSAmax (p = 0.012) and IEP (p = 0.020) showed significant statistical differences. The multivariate regression analysis suggested that CSAmax (in CEM or MR) and %RSCC were independent predictors of DCISM (all p < 0.05). The area under the curve (AUC) of CSAmax (CEM), %RSCC (CEM), Logit(P) (CEM), and CSAmax (MR) were 0.764, 0.795, 0.842, and 0.739, respectively. There were no significant differences in DeLong's test for these values (all p > 0.10). DCISM was significantly associated with high nuclear grade, comedo type, high axillary lymph node (ALN) metastasis, and high Ki-67 positivity compared to DCIS (all p < 0.05). CONCLUSION: The tumor size (CSAmax), enhancement index (%RS), and internal enhancement pattern (IEP) were highly indicative of DCISM. DCISM tends to express more aggressive pathological features, such as high nuclear grade, comedo-type necrosis, ALN metastasis, and Ki-67 overexpression. As with MRI, CEM has the capability to help predict when DCISM is accompanying DCIS.

Sevoflurane blocks KLF5-mediated transcriptional activation of ITGB2 to inhibit macrophage infiltration in hepatic ischemia/reperfusion injury.

BACKGROUND: Sevoflurane (Sevo) preconditioning and postconditioning play a protective role against injury induced by hepatic ischemia/reperfusion (I/R). At the same time, the involvement of macrophage infiltration in this process and the precise mechanisms are unclear. Here, we designed this research to elucidate the protective effects of Sevo against hepatic I/R injury and the molecules involved. METHODS: The alleviating effect of Sevo on the liver injury was analyzed by liver function analysis, hematoxylin and eosin staining, Masson trichrome staining, terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling, western blot analysis and an enzyme-linked immunosorbent assay. An in vitro cell model was developed using alpha mouse liver 12 (AML12) cells, and the cell model was treated with oxygen-glucose deprivation and reoxygenation and Sevo. Multiple bioinformatics databases were used to screen transcriptional regulators related to hepatic I/R injury and the targets of Krueppel-like factor 5 (KLF5). KLF5 expression was artificially upregulated alone or with integrin beta-2 (ITGB2) knockdown to substantiate their involvement in Sevo-mediated hepatoprotection. RESULTS: Sevo protected the liver against I/R injury by reducing cell apoptosis and inflammatory response. KLF5 was upregulated in liver tissues following I/R injury, whereas KLF5 overexpression aggravated macrophage infiltration and liver injury induced by I/R injury. KLF5 bound to the promoter of ITGB2 to enhance ITGB2 transcription. Knockdown of ITGB2 reversed the aggravation of injury caused by KLF5 overexpression in mice and AML12 cells. CONCLUSIONS: Sevo blocked KLF5-mediated transcriptional activation of ITGB2, thereby inhibiting macrophage infiltration in hepatic I/R injury.

Nivalones CF, four new meroterpenoids from Rhododendron nivale.

Four new meroterpenoids, namely nivalones CF (1-4), along with a known meroterpenoid, cannabiorcicyclolic acid (5), were isolated from the branches and leaves of Rhododendron nivale. The chemical structures of compounds 1-4 were elucidated through comprehensive spectroscopic analyses, including NMR, UV-Vis, IR, ECD spectroscopy, as well as HR-ESI-MS. The isolated compounds were evaluated for their anti-inflammatory and neuroprotective properties. The inhibitory activity of compound 5 against lipopolysaccharide (LPS)-induced nitric oxide (NO) production was initially demonstrated, showcasing an IC50 value of 21.1 µM. Additionally, both compounds 2 and 5 displayed a notable effect on the viability of H2O2-damaged SH-SY5Y cells, indicating their significant neuroprotection effects.

Environmental sustainability practice of sewage sludge and low-rank coal co-pyrolysis: A comparative life cycle assessment study.

This study attempts to bridge the current research gaps related to the environmental burdens of low-rank coal (LRC) and sewage sludge (SS) co-pyrolysis potentially. The life cycle assessment (LCA), energy recovery and sensitivity analysis were investigated for different proportions of LRC and SS (co-)pyrolysis. The results showed that the LRC/SS pyrolysis mitigated the environmental burden with an average improvement of 43 % across 18 impact categories compared with SS pyrolysis. The best net values of energy and carbon credits were identified in SL-4 with -3.36 kWh/kg biochar and -1.10 CO2-eq/kg biochar, respectively. This study firstly proposed an optimal LRC/SS co-feed proportion at 3 to 7, which achieves the acceptable environmental burden and satisfactory energy recovery. Moreover, sensitivity analysis demonstrated this proportion is robust and adaptable. LRC/SS co-pyrolysis is a promising and sustainable alternative for SS disposal, which could meet the imperative of carbon emission mitigation and resource recycling.

Morning Glory-Inspired Dual-Function Microcapsules for the Self-Reporting and Self-Healing of Electrothermal-Induced Damage of Electrical Devices.

The long-term operation of power equipment and power electronics can cause local overheating and discharges in the insulation material, resulting in irreversible insulation damage. Further development of such damage can eventually lead to equipment failure, but this problem is very difficult to solve. In this paper, inspired by how the petals of morning glory change color with the environment due to the presence of pigmented globules, a dual-function heat alert in the form of a self-healing (HASH) microcapsule with a nested structure is prepared by using microfluidic technology. By combination of the microcapsule with the insulation material, the local overheating in equipment can be detected promptly under live operating conditions without manual external intervention, and the defects that occur can be repaired autonomously. These HASH microcapsules can be pre-embedded in places at which the material is prone to overheating using artificial magnetic targeting. The doping of the matrix material with microcapsules does not cause any deterioration in its electrical or mechanical properties. This technology is expected to be applied to electrical equipment and electronic devices to allow for the early detection of local overheating and the autonomous repair of defects, thereby ensuring the safety of the equipment and improving its service life.

The causal relationship between atopic dermatitis and brain cancer: A bidirectional Mendelian randomization study.

BACKGROUND: Atopic dermatitis ranks among the prevalent skin disorders. Research has indicated a potential association with brain cancer. Yet, establishing a direct causal relationship between atopic dermatitis and brain cancer continues to be challenging. MATERIALS AND METHODS: We extracted single nucleotide polymorphisms (SNPs) significantly associated with atopic dermatitis (sample size = 382 254) at a genome-wide level from a large Finnish Genome-Wide Association Study (GWAS) dataset (n cases = 15 208, n controls = 367 046). Summary data for 372 622 cases of brain cancer (n cases = 606, n controls = 372 016) were obtained via the IEU Open GWAS database. We employed the Inverse Variance Weighted (IVW) method as our primary analytical approach for Mendelian Randomization (MR) analysis. Additionally, heterogeneity was measured using Cochran's Q value, and horizontal pleiotropy was evaluated using MR-Egger 、Mendelian Randomization Pleiotropy RESidual Sum and Outlier and leave-one-out analyses. RESULTS: The risk of brain cancer increases with the presence of atopic dermatitis, as evidenced by the odds ratios (ORs) and 95% confidence intervals (CIs),(OR = 1.0005; 95% CI = 1.0001, 1.0009; p = 0.0096). However, when conducting the analysis in reverse, no significant link was observed. CONCLUSION: The findings from our study indicate a causative link between atopic dermatitis and brain cancer, highlighting the importance of conducting broader clinical investigations into their potential association going forward.

Modified technique of Hepatojejunostomy for biliary tract reconstruction after resection of tumors affecting the perihilar region: a case series.

BACKGROUNDS: Radical resection is the most effective treatment for perihilar tumors. Biliary tract reconstruction after resection is one of the key steps in this surgery. Mucosa-to-mucosa cholangiojejunostomy is traditionally performed, in which the bile ducts at the resection margin are separately anastomosed to the jejunum. However, this approach is associated with long operative time and high risk of postoperative complications. The present study presents a modified technique of hepatojejunostomy and its outcomes. METHODS: The data of patients who underwent hepatojejunostomy using the modified technique at the Department of Hepatobiliary Surgery, Daping Hospital, Army Medical University, Chongqing, China, from January 2016 to December 2021, were retrospectively analyzed. RESULTS: A total of 13 patients with perihilar tumors underwent R0 resection and bilioenteric reconstruction using the modified hepatojejunostomy technique during the study period. During the operation, the alignment of the bile duct stumps was improved, the posterior wall of the anastomosis was reinforced, internal stents were placed in the smaller bile ducts, external stents were placed in the larger bile ducts, and hepatojejunostomy was performed using 4 - 0 prolene. No serious postoperative complications, such as death or bile leakage, occurred during the hospitalization. Furthermore, there were no cases of biliary stricture or cholangitis after the six-month follow-up period. CONCLUSION: The modified hepatojejunostomy technique is a safe and effective technique of biliary reconstruction after the resection of perihilar tumors. This can be easily performed for difficult cases with multiple bile ducts that require reconstruction after resection.

Compression Therapy after Thermal Ablation of Varicose Veins: A Meta-Analysis.

OBJECTIVE: To investigate whether compression therapy after thermal ablation of varicose veins can improve the prognosis of patients. METHODS: Systematic research were applied for Chinese and English electronic databases(PubMed, Web of Science, Cochrane Library, CNKI, Wanfang, VIP Databases). Eligible prospective studies that comparing the efficacy of compression therapy and non-compression therapy on patients after thermal ablation of varicose veins were included. The interest outcome such as pain, quality of life (QOL), venous clinical severity score (VCSS), time to return to work and complications were analyzed. RESULTS: 10 studies were of high quality, and randomized controlled trials involving 1,545 patients met the inclusion criteria for this study. At the same time, the meta-analysis showed that the application of compression therapy improved pain (SMD: -0.51, 95% CI: -0.95, -0.07) but exhibited no statistically significant effect on QOL (SMD: 0.04, 95% CI: -0.08, 0.16), VCSS (MD: -0.05, 95% CI: -1.19, 1.09), time to return to work (MD: -0.43, 95% CI: -0.90, 0.03), total complications (RR: 0.54, 95% CI: 0.27, 1.09), and thrombosis (RR: 0.71, 95% CI: 0.31, 1.62). CONCLUSION: Compression therapy after thermal ablation of varicose veins can slightly relieve pain, but it has not been found to be associated with improvement in other outcomes.

Utility of somatosensory- and motor-evoked potential change thresholds in surgical treatment for thoracic spinal stenosis based on different pathologies.

BACKGROUND CONTEXT: Thoracic spinal stenosis (TSS) is secondary to different pathologies that differ in clinical characteristics and surgical outcomes. PURPOSE: This study aimed to determine the optimal warning thresholds for combined somatosensory-evoked potentials (SSEP) and motor-evoked potentials (MEP) for predicting postoperative neurological deterioration in surgical treatment for TSS based on different pathologies. Additionally, we explored the correlation between SSEP/MEP monitoring and postoperative spinal neurological function. STUDY SETTING: Retrospective study. PATIENT SAMPLE: 205 patients. OUTCOME MEASURES: We obtained perioperative modified Japanese Orthopedic Association (mJOA) scores to assess spinal neurological function. METHODS: The data collected in this study included demographic data, intraoperative neurophysiological monitoring (IONM) signals, and perioperative neurological function assessments. To determine the optimal IONM warning threshold, a receiver operating characteristic (ROC) curve was used. Additionally, Pearson correlation analysis was conducted to determine the correlation between IONM signals and clinical neurological conditions. RESULTS: A total of 205 consecutive patients were eligible. Forty-one patients had thoracic disc herniation (TDH), 14 had ossification of the posterior longitudinal ligament (OPLL), 124 had ossification of the ligamentum flavum (OLF), and 26 had OPLL+OLF. The mean mJOA scores before surgery and 3 months after surgery were 7.0 and 7.9, respectively, resulting in a mean mJOA recovery rate (RR) of 23.1%. The average postoperative mJOA RRs for patients with TDH, OPLL, OLF, and OPLL+OLF were 24.8%, 10.4%, 26.8%, and 11.2%, respectively. Patients with OPLL+OLF exhibited a more stringent threshold for IONM changes. This included a lower amplitude cutoff value (a decrease of 49.0% in the SSEP amplitude and 57.5% in the MEP amplitude for short-term prediction) and a shorter duration of waveform change (19.5 minutes for SSEP and 22.5 minutes for MEP for short-term prediction). On the other hand, patients with TDH had more lenient IONM warning criteria (a decrease of 49.0% in SSEP amplitude and 77.5% in MEP amplitude for short-term prediction; durations of change of 25.5 minutes for SSEP and 32.5 minutes for MEP). However, OPLL patients or OLF patients had moderate and similar IONM warning thresholds. Additionally, there was a stronger correlation between the SSEP amplitude variability ratio and the JOA RR in OPLL+OLF patients, while the correlation was stronger between the MEP amplitude variability ratio and the JOA RR for the other three TSS pathologies. CONCLUSIONS: Optimal IONM change criteria for prediction vary depending on different TSS pathologies. The optimal monitoring strategy for prediction varies depending on TSS pathologies.

Microbial perspective on restoration of degraded urban soil using ornamental plants.

The urban soil where abandoned buildings are demolished is barren and structurally poor, and this degraded soil requires restoration. Ornamental plants enhance the urban environment, increase biodiversity, and affect soil physicochemical properties, microbial diversity; however, their effects remain unclear. Thus, in this study, a mixed-planting meadow consisting of 14 perennial ornamental flower species, including Iris tectorum, Iris lacteal, and Patrinia scabiosaefolia, etc. Was planted at a demolition site with sewage-contaminated soil in Beijing. Simultaneously, a single-planting lawn of I. tectorum was established in a nearby park. We aimed to examine soil physicochemical properties, sequence soil bacterial 16S rRNA and fungal ITS amplicons, and analyze soil microbial diversity and community structure at both sites at five time points in the year after planting, To explore the effect of herbaceous ornamental plants on degraded urban soil, we used FAPROTAX and FUNGuild to predict bacterial and fungal functions, the bin-based null model to evaluate the soil microbial community, and random matrix theory to construct soil microbial molecular networks. The mixed-planting meadow produced a visually appealing landscape and dynamic seasonal enrichment, significantly increasing soil total nitrogen (TN) and organic matter (SOM) contents by 1.99 and 1.21 times, respectively. TN had a positive correlation with soil microbial α diversity and community structure. Dominant phyla at both sites included Proteobacteria, Actinobacteria, and Ascomycota. Although soil microorganisms were primarily influenced by stochastic processes, stochasticity was notably higher in the mixed-planting meadow than in the single-planting lawn. The mixed-planting meadow significantly increased the relative abundance of beneficial microorganisms, improving nitrification and aerobic ammonium oxidation of soil bacteria, as well as symbiotroph of fungi. No significant changes were observed in the single-planting lawn. The mixed-planting meadow established a complex soil microbial molecular network, enhancing the correlation between bacteria and fungi and increasing the number of key microorganisms. Our findings suggest the potential of mixed-planting meadow in restoring degraded urban soils by influencing the soil microbial community and enhancing the ecological service function. Our study provides theoretical support for applying mixed-planting meadow communities to improve the soil environment of urban green spaces.

Self-Reporting Microsensors Inspired by Noctiluca Scintillans for Small-Defect Positioning and Electrical-Stress Visualization in Polymers.

Small defects induce concentrated electrical stress in dielectric polymers, leading to premature failure of materials. Existing sensing methods fail to effectively visualize these defects owing to the invisible-energy state of the electric field. Thus, it is necessary to establish a nondestructive method for the real-time detection of small defects in dielectric polymers. In this study, a self-reporting microsensor (SRM) inspired by Noctiluca scintillans is designed to endow materials with the ability of self-detection for defects and electrical stress. The SRM leverages the energy of a nearby electric field to emit measurable fluorescence, enabling defect localization and diagnosis as well as electrical-stress visualization. A controllable dielectric microsphere is constructed to achieve an adjustable electroluminescence threshold for the SRM, thereby increasing its detection accuracy while decreasing the electroluminescence threshold. The potential degradation in the polymer performance owing to SRM implantation is addressed by assembling long molecular chains on the SRM surface to spontaneously generate an interpenetrating network. Results of finite element analyses and experiments demonstrate that the SRM can effectively realize nondestructive visualization and positioning of small defects and concentrated electrical stress in polymers, positioning it as a promising sensing method for monitoring the electric field and charge distribution in materials.

Fungal community shows more variations by season and particle size than bacteria.

The global concern regarding the health risk associated with airborne microorganisms has prompted research in this field. However, there is a lack of systematic investigation into the particle-size distribution of airborne bacterial and fungal communities associated with seasons, which determines where they are deposited in the human respiratory tract. To address this gap, we conducted a study in Nanchang, located in central China, where we collected both coarse and fine particles during summer and winter seasons. The results demonstrated that microbial community exhibited obvious seasonal and particle-size variations except bacterial community in fine particles. Certain taxa (e.g., Bacteroidales, Ktedonobacterales, Capnodiales) displayed either seasonal and/or particle-size preferences. Furthermore, airborne microorganisms in coarse particles were more sensitive to season and particle size compared to those in fine particles, with fungal community being more susceptible than bacterial community. The susceptibility can be attributed to their high vulnerability to air pollutants and meteorological conditions, primarily PM2.5 and PM10. Additionally, a greater relative abundance of pathogenic fungi was observed in fine particles, even though microbial diversity in coarse particles was noticeably higher than that in fine particles. Furthermore, some predominant pathogens such as Alternaria, Nigrospora, and Escherichia-Shigella not only had particle size and/or seasonal preferences, but also were strongly correlated with environmental factors. This study advances our understanding of atmospheric pathogenic microorganisms and highlights the fungal health threat.

A fusion protein of vimentin with Fc fragment inhibits Japanese encephalitis virus replication.

Japanese encephalitis virus (JEV), a member of the Flaviviridae family and a flavivirus, is known to induce acute encephalitis. Vimentin protein has been identified as a potential receptor for JEV, engaging in interactions with the viral membrane protein. The Fc fragment, an integral constituent of immunoglobulins, plays a crucial role in antigen recognition by dendritic cells (DCs) or phagocytes, leading to subsequent antigen presentation, cytotoxicity, or phagocytosis. In this study, we fused the receptor of JEV vimentin with the Fc fragment of IgG and expressed the resulting vimentin-Fc fusion protein in Escherichia coli. Pull-down experiments demonstrated the binding ability of the vimentin-Fc fusion protein to JEV virion in vitro. Additionally, we conducted inhibition assays at the cellular level, revealing the ability of vimentin-Fc protein suppressing JEV replication, it may be a promising passive immunotherapy agent for JEV. These findings pave the way for potential therapeutic strategies against JEV.

Oncogenic KRAS induces arginine auxotrophy and confers a therapeutic vulnerability to SLC7A1 inhibition in non-small cell lung cancer.

The urea cycle is frequently rewired in cancer cells to meet the metabolic demands of cancer. Elucidation of the underlying mechanism by which oncogenic signaling mediates urea cycle reprogramming could help identify targetable metabolic vulnerabilities. In this study, we discovered that oncogenic activation of KRAS in non-small cell lung cancer (NSCLC) silenced the expression of argininosuccinate synthase 1 (ASS1), a urea cycle enzyme that catalyzes the production of arginine from aspartate and citrulline, and thereby diverted the utilization of aspartate to pyrimidine synthesis to meet the high demand for DNA replication. Specifically, KRAS signaling facilitated a hypo-acetylated state in the promoter region of the ASS1 gene in a histone deacetylase 3 (HDAC3)-dependent manner, which in turn impeded the recruitment of c-MYC for ASS1 transcription. ASS1 suppression in KRAS-mutant NSCLC cells impaired the biosynthesis of arginine and rendered a dependency on the arginine transmembrane transporter SLC7A1 to import extracellular arginine. Depletion of SLC7A1 in both patient-derived organoid and xenograft models inhibited KRAS-driven NSCLC growth. Together, these findings uncover the role of oncogenic KRAS in rewiring urea cycle metabolism and identify SLC7A1-mediated arginine uptake as a therapeutic vulnerability for treating KRAS-mutant NSCLC.

Transplantation of Cold-Stimulated Subcutaneous Adipose Tissue Improves Fat Retention and Recipient Metabolism.

BACKGROUND: Induction of beige fat for grafting is an emerging transplantation strategy. However, safety concerns associated with pharmaceutical interventions limits its wider application. Moreover, as a special type of fat with strong metabolic functions, the effect of metabolism of recipients after beige fat grafting has not been explored in plastic surgery domain. OBJECTIVES: To explore whether cold-induced inguinal white adipose tissue(iWAT) transplantation has a higher retention rate and beneficial effects on recipient metabolism. METHODS: The mice were subjected to cold stimulation for 48 hours to induce the browning of iWAT and harvested immediately. Subsequently, each C57/BL6 mouse received 0.2 ml cold-induced iWAT or normal iWAT transplantation. Fat grafts and recipients' iWAT, epididymal adipose tissue (epiWAT) and brown adipose tissue (BAT) were harvested at 8 weeks after operation. Immunofluorescence staining, real-time PCR and western blot were used for histological and molecular analysis. RESULTS: Cold-induced iWAT grafting has a higher retention rate (67.33%±1.74% vs. 55.83% ± 2.94%, P < 0.01) and more satisfactory structural integrity. Histological changes identified the better adipose tissue homeostasis after cold challenge, including abundant smaller adipocytes, higher levels of adipogenesis, angiogenesis, and proliferation, but lower levels of fibrosis. More importantly, cold-induced iWAT grafting suppressed the inflammation of epiWAT caused by conventional fat grafting, and activated the glucose metabolism and thermogenic activity of recipients' adipose tissues. CONCLUSIONS: Cold-induced iWAT grafting was an effective non-pharmacological intervention strategy to improve the retention rate and grafts' homeostasis. Furthermore, it improved the adverse effects caused by traditional fat grafting, but bring metabolic benefits.

The rat as a novel model for chronic rotator cuff injuries.

Chronic rotator cuff injuries (CRCIs) still present a great challenge for orthopaedics surgeons. Many new therapeutic strategies are developed to facilitate repair and improve the healing process. However, there is no reliable animal model for chronic rotator cuff injury research. To present a new valuable rat model for future chronic rotator cuff injuries (CRCIs) repair studies, and describe the changes of CRCIs on the perspectives of histology, behavior and MRI. Sixty male Wistar rats were enrolled and underwent surgery of the left shoulder joint for persistent subacromial impingement. They were randomly divided into experimental group (n = 30, a 3D printed PEEK implant shuttled into the lower surface of the acromion) and sham operation group (n = 30, insert the same implant, but remove it immediately). Analyses of histology, behavior, MRI and inflammatory pain-related genes expression profiles were performed to evaluate the changes of CRCIs. After 2-weeks running, the rats in the experimental group exhibited compensatory gait patterns to protect the injured forelimb from loading after 2-weeks running. After 8-weeks running, the rats in the experimental group showed obvious CRCIs pathological changes: (1) acromion bone hyperplasia and thickening of the cortical bone; (2) supraspinatus muscle tendon of the humeral head: the bursal-side tendon was torn and layered with disordered structure, forming obvious gaps; the humeral-side tendon is partially broken, and has a neatly arranged collagen. Partial fat infiltration is found. The coronal T2-weighted images showed that abnormal tendon-to-bone junctions of the supraspinatus tendon. The signal intensity and continuity were destroyed with contracted tendon. At the nighttime, compared with the sham operation group, the expression level of IL-1ß and COX-2 increased significantly (P = 0063, 0.0005) in the experimental group. The expression of COX-2 in experimental group is up-regulated about 1.5 times than that of daytime (P = 0.0011), but the expression of IL-1ß, TNF-a, and NGF are all down-regulated (P = 0.0146, 0.0232, 0.0161). This novel rat model of chronic rotator cuff injuries has the similar characteristics with that of human shoulders. And it supplies a cost-effective, reliable animal model for advanced tissue engineered strategies and future therapeutic strategies.

Intestinal epithelial Krüppel-like factor 4 alleviates endotoxemia and atherosclerosis through improving NF-κB/miR-34a-mediated intestinal permeability.

Maintenance of intestinal barrier function contributes to gastrointestinal homeostasis and therefore cardiovascular diseases. A number of studies show that intestinal permeability is affected by excessive inflammatory responses. Krüppel-like factor (KLF) 4 is one of the critical transcriptional factors, which controls multiple immune responses. In this study we investigated the role of KLF4 in regulating intestinal inflammation and permeability during the atherosclerotic process. Atherosclerotic model was established in ApoE-/- mice by feeding a high fat high cholesterol (HFHC) diet. We showed that colon expression levels of KLF4 and tight junction proteins were significantly decreased whereas inflammatory responses increased in atherosclerotic mice. Overexpression of colon epithelial Klf4 decreased atherosclerotic plaque formation and vascular inflammation in atherosclerotic mice, accompanied by remarkable suppression of intestinal NF-κB activation. We found that overexpression of epithelial Klf4 in atherosclerotic mice significantly increased intestinal tight junction expression and ameliorated endotoxemia, whereas replenishment of LPS abolished these benefits. Overexpression of Klf4 reversed LPS-induced permeability and downregulation of ZO-1 and Occludin in Caco-2 cells in vitro. HFHC diet stimulated the expression of epithelial microRNA-34a, whereas silence of epithelial Klf4 abolished the benefits of microRNA-34a sponge, a specific miR-34a inhibitor, on intestinal permeability and atherosclerotic development. A clinical cohort of 24 atherosclerotic patients supported colon KLF4/NF-κB/tight junction protein axis mediated intestine/cardiovascular interaction in patients with atherosclerosis. Taken together, intestinal epithelial KLF4 protects against intestinal inflammation and barrier dysfunction, ameliorating atherosclerotic plaque formation.

Comparative analysis of the organelle genomes of Aconitum carmichaelii revealed structural and sequence differences and phylogenetic relationships.

In this study, we conducted an assembly and analysis of the organelle genomes of Aconitum carmichaelii. Our investigation encompassed the examination of organelle genome structures, gene transfer events, and the environmental selection pressures affecting A. carmichaelii. The results revealed distinct evolutionary patterns in the organelle genomes of A. carmichaelii. Especially, the plastome exhibited a more conserved structure but a higher nucleotide substitution rate (NSR), while the mitogenome displayed a more complex structure with a slower NSR. Through homology analysis, we identified several instances of unidirectional protein-coding genes (PCGs) transferring from the plastome to the mitogenome. However, we did not observe any events which genes moved from the mitogenome to the plastome. Additionally, we observed multiple transposable element (TE) fragments in the organelle genomes, with both organelles showing different preferences for the type of nuclear TE insertion. Divergence time estimation suggested that rapid differentiation occurred in Aconitum species approximately 7.96 million years ago (Mya). This divergence might be associated with the reduction in CO2 levels and the significant uplift of the Qinghai-Tibet Plateau (QTP) during the late Miocene. Selection pressure analysis indicated that the dN/dS values of both organelles were less than 1, suggested that organelle PCGs were subject to purification selection. However, we did not detect any positively selected genes (PSGs) in Subg. Aconitum and Subg. Lycoctonum. This observation further supports the idea that stronger negative selection pressure on organelle genes in Aconitum results in a more conserved amino acid sequence. In conclusion, this study contributes to a deeper understanding of organelle evolution in Aconitum species and provides a foundation for future research on the genetic mechanisms underlying the structure and function of the Aconitum plastome and mitogenome.

Modulation of plasmacytoid dendritic cell and CD4+ T cell differentiation accompanied by upregulation of the cholinergic anti-inflammatory pathway induced by enterovirus 71.

Enterovirus 71 (EV71) is a neurotropic enterovirus associated with hand, foot, and mouth disease (HFMD) fatalities. In this study, we investigated the impact of EV71 on plasmacytoid dendritic cells (pDCs) and CD4+ T cells. The results showed that pDCs were promptly activated, secreting interferon (IFN)-α and inducing CD4+ T cell proliferation and differentiation during early EV71 infection. This initiated adaptive immune responses and promoted proinflammatory cytokine production by CD4+ T cells. Over time, viral nucleic acids and proteins were synthesized in pDCs and CD4+ T cells. Concurrently, the cholinergic anti-inflammatory pathway (CAP) was activated, exhibiting an anti-inflammatory role. With constant viral stimulation, pDCs and CD4+ T cells showed reduced differentiation and cytokine secretion. Defects in pDCs were identified as a key factor in CD4+ T cell tolerance. CAP had a more significant regulatory effect on CD4+ T cells than on pDCs and was capable of inhibiting inflammation in these cells.

Non-invasive measurements of blood glucose levels by time-gating mid-infrared optoacoustic signals.

Non-invasive glucose monitoring (NIGM) represents an attractive alternative to finger pricking for blood glucose assessment and management of diabetes. Nevertheless, current NIGM techniques do not measure glucose concentrations in blood but rely on indirect bulk measurement of glucose in interstitial fluid, where glucose is diluted and glucose dynamics are different from those in the blood, which impairs NIGM accuracy. Here we introduce a new biosensor, termed depth-gated mid-infrared optoacoustic sensor (DIROS), which allows, for the first time, non-invasive glucose detection in blood-rich volumes in the skin. DIROS minimizes interference caused by the stratum corneum and other superficial skin layers by time-gating mid-infrared optoacoustic signals to enable depth-selective localization of glucose readings in skin. In measurements on the ears of (female) mice, DIROS displays improved accuracy over bulk-tissue glucose measurements. Our work demonstrates how signal localization can improve NIGM accuracy and positions DIROS as a holistic approach, with high translational potential, that addresses a key limitation of current NIGM methods.