Anatomical changes and dosimetric analysis of the neck region based on FBCT for nasopharyngeal carcinoma patients during radiotherapy.

BACKGROUND: The study aimed to investigate anatomical changes in the neck region and evaluate their impact on dose distribution in patients with nasopharyngeal carcinoma (NPC) undergoing intensity modulated radiation therapy (IMRT). Additionally, the study sought to determine the optimal time for replanning during the course of treatment. METHODS: Twenty patients diagnosed with NPC underwent IMRT, with weekly pretreatment kV fan beam computed tomography (FBCT) scans in the treatment room. Metastasized lymph nodes in the neck region and organs at risk (OARs) were redelineation using the images from the FBCT scans. Subsequently, the original treatment plan (PLAN0) was replicated to each FBCT scan to generate new plans labeled as PLAN 1-6. The dose-volume histograms (DVH) of the new plans and the original plan were compared. One-way repeated measure ANOVA was utilized to establish threshold(s) at various time points. The presence of such threshold(s) would signify significant change(s), suggesting the need for replanning. RESULTS: Progressive volume reductions were observed over time in the neck region, the gross target volume for metastatic lymph nodes (GTVnd), as well as the submandibular glands and parotids. Compared to PLAN0, the mean dose (Dmean) of GTVnd-L significantly increased in PLAN5, while the minimum dose covering 95% of the volume (D95%) of PGTVnd-L showed a significant decrease from PLAN3 to PLAN6. Similarly, the Dmean of GTVnd-R significantly increased from PLAN4 to PLAN6, whereas the D95% of PGTVnd-R exhibited a significant decrease during the same period. Furthermore, the dose of bilateral parotid glands, bilateral submandibular glands, brainstem and spinal cord was gradually increased in the middle and late period of treatment. CONCLUSION: Significant anatomical and dosimetric changes were noted in both the target volumes and OARs. Considering the thresholds identified, it is imperative to undertake replanning at approximately 20 fractions. This measure ensures the delivery of adequate doses to target volumes while mitigating the risk of overdosing on OARs.

Daphnetin Preconditioning Decreases Cardiac Injury and Susceptibility to Ventricular Arrhythmia following Ischaemia-Reperfusion through the TLR4/MyD88/NF-Κb Signalling Pathway.

BACKGROUND/AIMS: Daphnetin (7,8-dihydroxycoumarin, DAP) exhibits various bioactivities, such as anti-inflammatory and antioxidant activities. However, the role of DAP in myocardial ischaemia/reperfusion (I/R) injury and I/R-related arrhythmia is still uncertain. This study aimed to investigate the mechanisms underlying the effects of DAP on myocardial I/R injury and electrophysiological properties in vivo and in vitro. METHODS: Myocardial infarct size was measured by triphenyltetrazolium chloride staining. Cardiac function was assessed by echocardiographic and haemodynamic analyses. The levels of creatine kinase-MB, lactate dehydrogenase, malondialdehyde, superoxide dismutase, interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-α) were detected using commercial kits. Apoptosis was measured by terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labelling staining and flow cytometry. The viability of H9c2 cells was determined by the Cell Counting Kit-8 assay. In vitro, the levels of IL-6 and TNF-α were measured by quantitative PCR. The expression levels of proteins associated with apoptosis, inflammation, and the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor kappa B (TLR4/MyD88/NF-κB) signalling pathway were detected by Western blot analysis. The RR, PR, QRS, and QTc intervals were assessed by surface ECG. The 90% action potential duration (APD90), threshold of APD alternans, and ventricular tachycardia inducibility were measured by the Langendorff perfusion technique. RESULTS: DAP preconditioning decreased myocardial I/R injury and hypoxia/reoxygenation (H/R) injury in cells. DAP preconditioning improved cardiac function after myocardial I/R injury. DAP preconditioning also suppressed apoptosis, attenuated oxidative stress, and inhibited inflammatory responses in vivo and in vitro. Furthermore, DAP preconditioning decreased the susceptibility to ventricular arrhythmia after myocardial I/R. Finally, DAP preconditioning inhibited the expression of TLR4, MyD88, and phosphorylated NF-κB (p-NF-κB)/P65 in mice subjected to I/R and cells subjected to H/R. CONCLUSIONS: DAP preconditioning protected against myocardial I/R injury and decreased susceptibility to ventricular arrhythmia by inhibiting the TLR4/MyD88/NF-κB signalling pathway.

MD1 Depletion Predisposes to Ventricular Arrhythmias in the Setting of Myocardial Infarction.

BACKGROUND: Myeloid differentiation protein 1 (MD1) is expressed in the human heart and is a negative regulator of Toll-like receptor 4 (TLR4) signalling. MD1 exerts anti-arrhythmic effects. AIM: The aim of this study was to determine the role of MD1 in myocardial infarction (MI)-related ventricular arrhythmias (VAs). METHOD: Myocardial infarction was induced by surgical ligation of the left anterior coronary artery in MD1 knockout (KO) mice and their wild-type littermates. Myocardial infarction-induced vulnerability to VAs and its underlying mechanisms were evaluated. RESULTS: Myeloid differentiation protein 1 was downregulated in the MI mice. Myeloid differentiation protein 1 deficiency decreased post-MI left ventricular (LV) function and increased the infarct size. The MI mice exhibited prolonged action potential duration (APD), enhanced APD alternans thresholds, and a higher incidence of VAs. Myocardial infarction-induced LV fibrosis and inflammation decreased the expression levels of Kv4.2, Kv4.3, Kv1.5, and Kv2.1, increased Cav1.2 expression, and disturbed Ca2+ handling protein expression. These MI-induced adverse effects were further exacerbated in KO mice. Mechanistically, MD1 deletion markedly enhanced the activation of the TLR4/calmodulin-dependent protein kinase II (CaMKII) signalling pathway in post-MI mice. CONCLUSIONS: Myeloid differentiation protein 1 deletion increases the vulnerability to VAs in post-MI mice. This is mainly caused by the aggravated maladaptive LV fibrosis and inflammation and interference with the expressions of ion channels and Ca2+ handling proteins, which is related to enhanced activation of the TLR4/CaMKII signalling pathway.

Myeloid differentiation protein 1 protected myocardial function against high-fat stimulation induced pathological remodelling.

Myeloid differentiation 1 (MD-1) is a secreted protein that regulates the immune response of B cell through interacting with radioprotective 105 (RP105). Disrupted immune response may contribute to the development of cardiac diseases, while the roles of MD-1 remain elusive. Our studies aimed to explore the functions and molecular mechanisms of MD-1 in obesity-induced cardiomyopathy. H9C2 myocardial cells were treated with free fatty acid (FFA) containing palmitic acid and oleic acid to challenge high-fat stimulation and adenoviruses harbouring human MD-1 coding sequences or shRNA for MD-1 overexpression or knockdown in vitro. MD-1 overexpression or knockdown transgenic mice were generated to assess the effects of MD-1 on high-fat diet (HD) induced cardiomyopathy in vivo. Our results showed that MD-1 was down-regulated in H9C2 cells exposed to FFA stimulation for 48 hours and in obesity mice induced by HD for 20 weeks. Both in vivo and in vitro, silencing of MD-1 accelerated myocardial function injury induced by HD stimulation through increased cardiac hypertrophy and fibrosis, while overexpression of MD-1 alleviated the effects of HD by inhibiting the process of cardiac remodelling. Moreover, the MAPK and NF-κB pathways were overactivated in MD-1 deficient mice and H9C2 cells after high-fat treatment. Inhibition of MAPK and NF-κB pathways played a cardioprotective role against the adverse effects of MD-1 silencing on high-fat stimulation induced pathological remodelling. In conclusion, MD-1 protected myocardial function against high-fat stimulation induced cardiac pathological remodelling through negative regulation for MAPK/NF-κB signalling pathways, providing feasible strategies for obesity cardiomyopathy.

Antibody drug conjugates of cleavable amino-alkyl and aryl maytansinoids.

Natural products have been used for many medicinal purposes for centuries. Antibody drug conjugates (ADCs) have utilized this rich source of small molecule therapeutics to produce several clinically useful treatments. ADCs based on the natural product maytansine have been successful clinically. The authors further the utility of the anti-cancer natural product maytansine by developing efficacious payloads and linker-payloads for conjugating to antibodies. The success of our approach was realized in the EGFRvIII targeting ADC EGFRvIII-16. The ADC was able to regress tumors in 2 tumor models (U251/EGFRvIII and MMT/EGFRvIII). When compared to a positive control ADC, the efficacy observed was similar or improved while the isotype control ADCs had no effect.

[Study on High-yield Cultivation Measures for Arctii Fructus].

OBJECTIVE: To find out the high yield cultivation measures for Arctii Fructus. METHODS: Completely randomized block experiment design method was used in the field planting, to analyze the effect of different cultivation way on agronomic characters, phenological phase,quality and quantity of Arctii Fructus. RESULTS: Arctium lappa planted on August 28 had the best results of plant height, thousand seeds weight and yield. The highest yield of Arctii Fructus was got at the density of 1,482 plants/667 m2. Arctiin content was in an increase trend with the planting time delay and planting density increasing. The plant height, thousand seeds weight, yield and arctiin content by split application of fertilizer were significantly higher than that by one-time fertilization. Compared with open field Arctium lappa, plant height, yield, arctiin content and relative water content of plastic film mulching Arctium lappa was higher by 7.74%, 10.87%, 6.38% and 24.20%, respectively. In the topping Arctium lappa, the yield was increased by 11.09%, with 39. 89% less branching number. Early planting time and topping shortened the growth cycle of Arctium lappa plant. CONCLUSION: The high-yield cultivation measures of Arctii Fructus are: around August 28 to sowing, planting density of 1 482 plants/667 m2, split application of fertilizer for four times, covering film on surface of the soil and topping in bolting.

Mindfulness and acceptance-based training for elite adolescent athletes: a mixed-method exploratory study.

Objectives: This study aimed to examine the effectiveness of a specifically designed mindfulness-acceptance-insight-commitment (MAIC) training program on relevant psychological factors (i.e., mindfulness, acceptance, performance-related satisfaction) as well as sport training performance for elite adolescent athletes from Hong Kong. And it also aimed to explore the athletes' real experiences (i.e., receptiveness and perceptions) of completing the MAIC program. Methods and design: The mixed-method was used in this study, including a randomized controlled trial (RCT) and a qualitative exploration. The RCT employed a 2 (groups) x 3 (data collection points) design involving 40 elite adolescent athletes from the Hong Kong Sports Institute (HKSI). These athletes were randomly assigned to either the MAIC training group (MT; n = 20, Mage = 15.65) or the control group (CG; n = 20, Mage = 15.85) to further test the effectiveness of the MAIC intervention on mindfulness, acceptance, performance-related satisfaction, and sport training performance. Subsequent to the RCT, the qualitative exploration was used to explore the athletes' real experiences towards the MAIC program. In the qualitative exploration, all athletes who participated in the MAIC program were invited to participate in voluntary semi-structured interviews. Of these, 14 athletes chose to take part in the interviews. The RCT employed a 2×3 mixed-design ANOVA, while thematic analysis was applied to the qualitative exploration. Results: The results revealed that the MAIC training program significantly enhanced athletes' mindfulness, acceptance, satisfaction with performance, and sport training performance. However, these effects diminished at the follow-up assessment compared to post-training. Notably, the acceptance level of MT athletes did not significantly differ from CG athletes at the follow-up assessment. Additionally, the qualitative analysis identified four key dimensions: (a) Attitude towards MAIC training, (b) Reflection on the MAIC learning process, (c) Outcomes of MAIC training, and (d) Recommendations for future MAIC training. Overall, the qualitative findings complemented and reinforced the quantitative results, offering deeper insights into athletes' experiences and valuable suggestions for further enhancing the MAIC program. Conclusion: The findings suggested that the specifically designed MAIC training program in this study effectively enhanced sport training performance and various psychological factors among elite adolescent athletes from Hong Kong. Nevertheless, further investigations are still required to comprehensively evaluate and further develop the MAIC training program.

Effect of miR-1297 on Kidney Injury in Rats with Diabetic Nephropathy through the PTEN/PI3K/AKT Pathway.

PURPOSE: This study aimed to determine the influence of miR-1297 on kidney injury in rats with diabetic nephropathy (DN) and its causal role. METHODS: A DN rat model was established through right kidney resection and intraperitoneal injection of streptozotocin (STZ). Sham rats did not undergo right kidney resection or STZ injection. The DN rats were divided into the DN model and antagomiR-1297 treatment groups. Kidney morphology was observed using hematoxylin and eosin staining. Renal function indices, including blood urea nitrogen (BUN), serum creatinine (SCr), and urinary protein, were measured using kits. Levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1ß, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were determined through enzyme-linked immunosorbent assay (ELISA). Fibrin (FN), collagen type I (Col I), and α-smooth muscle actin (α-SMA) were assessed through western blotting and real-time reverse transcription-polymerase chain reaction. Apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. miR-1297 targets were predicted using bioinformatic software and verified through luciferase reporter assay. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway expression was analyzed through western blotting. RESULTS: AntagomiR-1297 reduced BUN (p = 0.005), SCr (p = 0.012), and urine protein (p < 0.001) levels and improved kidney tissue morphology. It prevented renal interstitial fibrosis by decreasing FN, Col I, and α-SMA protein levels (all p < 0.001). AntagomiR-1297 increased SOD (p = 0.001) and GSH-Px (p = 0.002) levels. Additionally, it reduced levels of cell inflammatory factors, including TNF-α, IL-6, and IL-1ß (all p < 0.001), and alleviated apoptosis (p < 0.001) in rat kidney tissue with DN. miR-1297 was pinpointed as a target for PTEN. AntagomiR-1297 increased PTEN expression and suppressed PI3K and AKT phosphorylation (all p < 0.001). CONCLUSIONS: AntagomiR-1297 can mitigate renal fibrosis, renal inflammation, apoptosis, and oxidative stress levels through the PTEN/PI3K/AKT pathway.

Surface guided radiation therapy with an innovative open-face mask and mouth bite: patient motion management in brain stereotactic radiotherapy.

INTRODUCTION: To guarantee treatment reproducibility and stability, immobilization devices are essential. Additionally, surface-guided radiation therapy (SGRT) serves as an accurate complement to frameless stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) by aiding patient positioning and real-time monitoring, especially when non-coplanar fields are in use. At our institute, we have developed a surface-guided SRS (SG-SRS) workflow that incorporates our innovative open-face mask (OM) and mouth bite (MB) to guarantee a precise and accurate dose delivery. METHODS: This study included 40 patients, and all patients were divided into closed mask (CM) and open-face mask (OM) groups according to different positioning flow. Cone beam computed tomography (CBCT) scans were performed, and the registration results were recorded before and after the treatment. Then Bland-Altman method was used to analyze the consistency of AlignRT-guided positioning errors and CBCT scanning results in the OM group. The error changes between 31 fractions in one patient were recorded to evaluate the feasibility of monitoring during treatment. RESULTS: The median of translation error between stages of the AlignRT positioning process was (0.03-0.07) cm, and the median of rotation error was (0.20-0.40)°, which were significantly better than those of the Fraxion positioning process (0.09-0.11) cm and (0.60-0.75)°. The mean bias values between the AlignRT guided positioning errors and CBCT were 0.01 cm, - 0.07 cm, 0.03 cm, - 0.30°, - 0.08° and 0.00°. The 31 inter-fractional errors of a single patient monitored by SGRT were within 0.10 cm and 0.50°. CONCLUSIONS: The application of the SGRT with an innovative open-face mask and mouth bite device could achieve precision positioning accuracy and stability, and the accuracy of the AlignRT system exhibits excellent constancy with the CBCT gold standard. The non-coplanar radiation field monitoring can provide reliable support for motion management in fractional treatment.

Analysis of Individualized Silicone Rubber Bolus Using Fan Beam Computed Tomography in Postmastectomy Radiotherapy: A Dosimetric Evaluation and Skin Acute Radiation Dermatitis Survey.

Objective: To investigate the dosimetric effects of using individualized silicone rubber (SR) bolus on the target area and organs at risk (OARs) during postmastectomy radiotherapy (PMRT), as well as evaluate skin acute radiation dermatitis (ARD). Methods: A retrospective study was performed on 30 patients with breast cancer. Each patient was prepared with an individualized SR bolus of 3 mm thickness. Fan-beam computed tomography (FBCT) was performed at the first and second fractions, and then once a week for a total of 5 times. Dosimetric metrics such as homogeneity index (HI), conformity index (CI), skin dose (SD), and OARs including the heart, lungs, and spinal cord were compared between the original plan and the FBCTs. The acute side effects were recorded. Results: In targets' dosimetric metrics, there were no significant differences in Dmean and V105% between planning computed tomography (CT) and actual treatments (P > .05), while the differences in D95%, V95%, HI, and CI were statistically significant (P < .05). In OARs, there were no significant differences between the Dmean, V5, and V20 of the affected lung, V5 of the heart and Dmax of the spinal cord (P > .05) except the V30 of affected lung, which was slightly lower than the planning CT (P < .05). In SD, both Dmax and Dmean in actual treatments were increased than plan A, and the difference was statistically significant (P < .05), while the skin-V20 and skin-V30 has no difference. Among the 30 patients, only one patient had no skin ARD, and 5 patients developed ARD of grade 2, while the remaining 24 patients were grade 1. Conclusion: The OR bolus showed good anastomoses and high interfraction reproducibility with the chest wall, and did not cause deformation during irradiation. It ensured accurate dose delivery of the target and OARs during the treatment, which may increase SD by over 101%. In this study, no cases of grade 3 skin ARD were observed. However, the potential of using OR bolus to reduce grade 1 and 2 skin ARD warrants further investigation with a larger sample size.

Impact of myeloid differentiation protein 1 on cardiovascular disease.

Cardiovascular disease remains the leading cause of disability and mortality worldwide and a significant global burden. Many lines of evidence suggest complex remodeling responses to cardiovascular disease, such as myocardial ischemia, hypertension and valve disease, which lead to poor clinical outcomes, including heart failure, arrhythmia and sudden cardiac death (SCD). The mechanisms underlying cardiac remodeling are closely related to reactive oxygen species (ROS) and inflammation. Myeloid differentiation protein 1 (MD1) is a secreted glycoprotein known as lymphocyte antigen 86. The complex of MD1 and radioprotective 105 (RP105) is an important regulator of inflammation and is involved in the modulation of vascular remodeling and atherosclerotic plaque development. A recent study suggested that the expression of MD1 in hypertrophic cardiomyopathy (HCM) patients is decreased compared with that in donor hearts. Therefore, MD1 may play an important role in the pathological processes of cardiovascular disease and have potential clinical value. Here, this review aims to discuss the current knowledge regarding the role of MD1 in the regulation of cardiac pathophysiology.

Association of triglyceride-glucose index with the prevalence of cardiovascular disease in malnourished/non-malnourished patients: a large cross-sectional study.

Background: Numerous investigations have demonstrated a strong association between the TyG (triglyceride-glucose) index, which is derived from lipid and glucose levels in the bloodstream, and the onset and progression of cardiovascular diseases (CVD). Blood glucose and blood lipids are affected by nutritional status, and few studies have explored whether the correlation between TyG index and the risk of CVD is affected by nutritional status. Aims: To investigate the connection between TyG index and the risk of CVD among individuals with varying nutritional statuses. Method: A total of 19,847 were included in the analysis, of which 15,955 participants were non-malnourished and 3,892 patients were malnourished. According to the TyG index quartile, the patients were categorized into four groups. Logistic regression analysis and restricted cubic spline was used to study the relationship between TyG index and the risk of CVD in normal and malnourished populations. Results: The results of the restricted cubic spline showed that the TyG index was positively associated with the risk of CVD in the non-malnourished population. The TyG index showed a U-shaped association with the risk of CVD in malnourished people. The result is consistent with that of logistic regression (Malnutrition: Group 2: OR: 1.14; 95% CI: 0.85-1.53; Group 3: OR: 1.36; 95% CI: 1.03-1.79; Group 4: OR: 1.72; 95% CI:1.31-2.25, P for trend <0.001; Non-malnutrition: Group 2: OR: 0.82; 95% CI: 0.46-1.48; Group 3: OR: 0.88; 95% CI: 0.49-1.57; Group 4: OR: 1.45; 95% CI:0.83-2.52, P for trend =0.067). Conclusions: The association between the TyG index and the risk of CVD varied depending on the nutritional states. When using TyG index to assess the risk of CVD, stratification combined with nutritional status helps to more accurately screen patients at high risk of CVD.

A pilot trial of consolidation bevacizumab after hypo-fractionated concurrent chemoradiotherapy in patients with unresectable locally advanced non-squamous non-small-cell lung cancer.

PURPOSE: To determine the feasibility of incorporating bevacizumab consolidation into hypo-fractionated concurrent chemoradiotherapy (hypo-CCRT) for patients with unresectable locally advanced non-squamous non-small-cell lung cancer (LA-NS-NSCLC). PATIENTS AND METHODS: Eligible patients were treated with hypo-RT (40Gy in 10 fractions) followed by hypo-boost (24-28Gy in 6-7 fractions), along with concurrent weekly chemotherapy. Patients who completed the hypo-CCRT without experiencing ≥G2 toxicities received consolidation bevacizumab every 3 weeks for up to 1 year, until disease progression or unacceptable treatment-related toxicities. The primary endpoint was the risk of G4 or higher hemorrhage. Secondary endpoints included progression-free survival (PFS), overall survival (OS), locoregional failure-free survival (LRFS), distant metastasis-free survival (DMFS), and objective response rate (ORR). All time-to-event endpoints (OS, PFS, LRFS, and DMFS) were measured from the start of radiotherapy. RESULTS: Between December 2017 and July 2020, a total of 27 patients were included in the analysis, with a median follow-up duration of 28.0 months. One patient (3.7%) developed G5 hemorrhage during bevacizumab consolidation. Additionally, seven patients (25.9%) had G3 cough and three patients (11.1%) experienced G3 pneumonitis. The ORR for the entire cohort was 92.6%. The median OS was 37.0 months (95% confidence interval, 8.9-65.1 months), the median PFS was 16.0 months (95% confidence interval, 14.0-18.0 months), the median LRFS was not reached, and the median DMFS was 18.0 months. CONCLUSIONS: This pilot study met its goal of demonstrating the tolerability of consolidation bevacizumab after hypo-CCRT. Further investigation of antiangiogenic and immunotherapy combinations in LA-NSCLC is warranted, while the potential for grade 3 respiratory toxicities should be taken into consideration.

Robust All-Solid-State Lithium Metal Batteries Enabled by a Composite Lithium Anode with Improved Bulk Li Diffusion Kinetics Properties.

All-solid-state batteries (ASSBs) with a Li metal anode are expected to be one of the most promising energy storage systems to achieve high energy density. However, the interfacial instability between the Li metal anode and solid-state electrolyte (SSE) limits the rate capability and cycling stability of ASSBs. The main issue is the formation of voids at the Li/SSE interface during Li stripping due to the slow diffusion of Li within the bulk Li metal, then increasing internal cell resistance and inducing the formation of lithium dendrites. To address these issues, a composite Li anode (LAO) composed by Li-Ag alloy and Li2O is constructed by mixing the stoichiometric metal Li and Ag2O directly. LAO anode is capable of improving bulk Li diffusion kinetics and inhibiting the formation of interfacial voids effectively, achieving a high critical current density over 1.5 mA cm-2 and long stable cycling over 1000 h at 1 mA cm-2. The ASSBs, employing LAO as the anode, Li6PS5Cl as the SSE, and LiCoO2 as the cathode, exhibit superior rate capability and stable cycling over 4000 cycles at 5 C. Moreover, ASSBs can operate stably with a high LiCoO2 loading of 17.8 mg cm-2 for more than 100 cycles at 0.2 C.

Effects of aerobic exercise on depression-like behavior and TLR4/NLRP3 pathway in hippocampus CA1 region of CUMS-depressed mice.

BACKGROUND AND PURPOSE: The paper observes regulation of the expression levels of NLRP3 and TLR4 in hippocampal CA1 neurons in CUMS mice by aerobic exercise with constructing CUMS depression mouse model, in order to explore the neuroprotective mechanism of aerobic exercise on the hippocampus of depressed mice. STUDY DESIGN AND METHOD: 24 healthy male 8-week-old C57BL/6 mice were randomly divided into CG, MG and ME. Thirteen stress-stimulating factors were randomly formulated into a CUMS stress-stimulating program. The mice were underwent 28 days of CUMS depression model, referenced clinical means for experimental research. The study was approved by the Ethics Committee of Yichun University (YCUEC IRB number LSK NO.2022.18). After model preparation, ME mice were subjected to moderate-intensity treadmill exercise training for 8 weeks. TST, FST and SPT were used to detect the depression-like behaviors of the mice in each group. Nissl staining was used to compare the cell morphology in the CA1 region of the mouse hippocampus. Immunohistochemical staining and western blot were used to detect the changes in the expression levels of NLRP3, TLR4 and other proteins in the CA1 region of the mouse hippocampus. RESULTS: The results of neurobehavioral assessment showed that, the immobility time of TST and FST were significantly increased, and SPT index was significantly decreased of MG mice. Compared with MG, ME mice significantly improved depression-like behaviors such as TST, FST and SPT index. Nissl staining showed that the morphology of neurons in CA1 region of hippocampus of MG mice were mostly vacuolar-like, with severe nuclear pyknosis. Abnormal morphological changes such as vacuolar-like and pyknotic pyknosis of neurons in the hippocampal CA1 region of ME mice were significantly reduced. Protein expression test showed that the number of NLRP3, TLR4, IL-1ß and IL-10 positive neurons in hippocampal CA1 region of MG mice increased significantly compared with CG, and the proportion of positive cells increased significantly, while NLRP3 and TLR4 positive neurons in the hippocampal CA1 region of ME mice were significantly reduced, the proportion of TLR4 positive cells was significantly reduced. CONCLUSION: Systematic moderate-intensity exercise can effectively improve the depression-like behavior of CUMS depressed mice through the expression of TLR4/NLRP3 inflammatory signaling pathway, and provide an effective experimental basis for the clinical rehabilitation treatment of depression.

Intelligent Classification Method of Archive Data Based on Multigranular Semantics.

With the rapid development of information technology, the amount of data in various digital archives has exploded. How to reasonably mine and analyze archive data and improve the effect of intelligent management of newly included archives has become an urgent problem to be solved. The existing archival data classification method is manual classification oriented to management needs. This manual classification method is inefficient and ignores the inherent content information of the archives. In addition, for the discovery and utilization of archive information, it is necessary to further explore and analyze the correlation between the contents of the archive data. Facing the needs of intelligent archive management, from the perspective of the text content of archive data, further analysis of manually classified archives is carried out. Therefore, this paper proposes an intelligent classification method for archive data based on multigranular semantics. First, it constructs a semantic-label multigranular attention model; that is, the output of the stacked expanded convolutional coding module and the label graph attention module are jointly connected to the multigranular attention Mechanism network, the weighted label output by the multigranularity attention mechanism network is used as the input of the fully connected layer, and the output value of the fully connected layer used to map the predicted label is input into a Sigmoid layer to obtain the predicted probability of each label; then, the model for training: use the multilabel data set to train the constructed semantic-label multigranularity attention model, adjust the parameters until the semantic-label multigranularity attention model converges, and obtain the trained semantic-label multigranularity attention model. Taking the multilabel data set to be classified as input, the semantic-label multigranularity attention model after training outputs the classification result.

Emerging roles of fibroblast growth factor 21 in critical disease.

In spite of the great progress in the management of critical diseases in recent years, its associated prevalence and mortality of multiple organ failure still remain high. As an endocrine hormone, fibroblast growth factor 21 (FGF21) functions to maintain homeostasis in the whole body. Recent studies have proved that FGF21 has promising potential effects in critical diseases. FGF21 has also been found to have a close relationship with the progression of critical diseases and has a great predictive function for organ failure. The level of FGF21 was elevated in both mouse models and human patients with sepsis or other critical illnesses. Moreover, it is a promising biomarker and has certain therapeutic roles in some critical diseases. We focus on the emerging roles of FGF21 and its potential effects in critical diseases including acute lung injury/acute respiratory distress syndrome (ALI/ARDS), acute myocardial injury (AMI), acute kidney injury (AKI), sepsis, and liver failure in this review. FGF21 has high application value and is worth further studying. Focusing on FGF21 may provide a new perspective for the management of the critical diseases.

MCC950 ameliorates ventricular arrhythmia vulnerability induced by heart failure.

MCC950, a specific NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inhibitor, has been reported to play a role in various cardiovascular diseases. However, its role in heart failure (HF)-induced ventricular arrhythmias (VAs) remains unclear. Hence, the present study aimed to clarify the role and underlying mechanisms of MCC950 in HF-induced VAs. Male C57BL/6 mice were induced with HF via transverse aortic constriction (TAC). Histological analysis, echocardiography, electrophysiological investigation, and western blot analysis were conducted to evaluate VA vulnerability induced by TAC and the potential mechanisms underlying the effects. MCC950 markedly improved cardiac function and decreased pulmonary edema induced by HF. Moreover, MCC950 also decreased VA vulnerability, as shown by the shortened QTc duration and action potential duration 90 (APD90), reduced APD alternans threshold, and decreased VA induction rate. Furthermore, MCC950 treatment significantly reversed TAC-induced cardiac hypertrophy and fibrosis. In addition, MCC950 administration increased the protein levels of ion channels (Kv4.2, KChIP2, and Cav1.2). Mechanistically, the above changes induced by MCC950 were due to the inhibition of the NLRP3 inflammasome. As a specific NLRP3 inhibitor, MCC950 significantly decreased HF-induced VA vulnerability by reversing cardiac structural remodeling and electrical remodeling, and the mechanism through which MCC950 exhibited this effect was inhibition of NLRP3 inflammasome activation.

Galectin-1 alleviates myocardial ischemia-reperfusion injury by reducing the inflammation and apoptosis of cardiomyocytes.

Myocardial ischemia-reperfusion injury (MIRI) is one of the leading causes of morbidity and mortality worldwide, for which there is no effective treatment. The present study aimed to assess novel methods of clinical MIRI treatment by studying the effects of galectin-1 (Gal-1) on MIRI. Male 2-month-old Sprague Dawley rats and the rat cardiomyocyte cell line H9c2 were utilized in the present study. A rat model of MIRI was constructed by ligating the left anterior descending coronary artery, which was subsequently treated with Gal-1. Differences in myocardial injury were then assessed by hematoxylin and eosin (H&E) staining. In addition, the levels of inflammation and apoptosis in rat myocardial tissue were determined by immunohistochemistry staining. Hypoxia-reoxygenation was used to construct a model of MIRI in H9c2 cells. The effect of Gal-1 on the apoptosis and viability of H9c2 cells was also verified by flow cytometry and a Cell Counting Kit-8 assay. The results of H&E staining revealed that Gal-1 alleviated MIRI. Echocardiography demonstrated that Gal-1 improved cardiac function in rats following MIRI. In addition, MIRI increased levels of inflammation and apoptosis in rat myocardial tissues, with Gal-1 treatment reversing this effect. In cellular experiments, Gal-1 served anti-inflammatory and anti-apoptotic effects in hypoxic/reoxygenated cardiomyocytes. In conclusion, Gal-1 served a significant protective effect on the myocardial tissue after ischemia-reperfusion by reducing the level of inflammation and apoptosis in cardiomyocytes.

Mitophagy: A potential therapeutic target for insulin resistance.

Glucose and lipid metabolism disorders caused by insulin resistance (IR) can lead to metabolic disorders such as diabetes, obesity, and the metabolic syndrome. Early and targeted intervention of IR is beneficial for the treatment of various metabolic disorders. Although significant progress has been made in the development of IR drug therapies, the state of the condition has not improved significantly. There is a critical need to identify novel therapeutic targets. Mitophagy is a type of selective autophagy quality control system that is activated to clear damaged and dysfunctional mitochondria. Mitophagy is highly regulated by various signaling pathways, such as the AMPK/mTOR pathway which is involved in the initiation of mitophagy, and the PINK1/Parkin, BNIP3/Nix, and FUNDC1 pathways, which are involved in mitophagosome formation. Mitophagy is involved in numerous human diseases such as neurological disorders, cardiovascular diseases, cancer, and aging. However, recently, there has been an increasing interest in the role of mitophagy in metabolic disorders. There is emerging evidence that normal mitophagy can improve IR. Unfortunately, few studies have investigated the relationship between mitophagy and IR. Therefore, we set out to review the role of mitophagy in IR and explore whether mitophagy may be a potential new target for IR therapy. We hope that this effort serves to stimulate further research in this area.